Author: "Tomio Ueno" / Search Limiters: Available in Library Collection - Searchworks@Jio Institute Digital Library Search Results

87 results on '"Tomio Ueno"'

1. The seven-day cumulative post-esophagectomy inflammatory response predicts cancer recurrence

Author: Yoshinori Fujiwara, Shunji Endo, Masaharu Higashida, Hisako Kubota, Kazuhiko Yoshimatsu, and Tomio Ueno
Subjects: Esophagectomy, Esophageal cancer, CRP, Prognosis, Complications, Surgery, RD1-811
Abstract: Abstract Background The relationship between postoperative cumulative systemic inflammation and cancer survival needs to be investigated. We developed an approach to the prognostication of postoperative esophageal cancer by establishing low and high cut-off values for the C-reactive protein (CRP) area under the curve (AUC) at 7 and 14 days after esophagectomy. Methods One hundred and twenty-five consecutive patients with biopsy-proven invasive esophageal squamous cell carcinoma (SCC) who underwent esophagectomies were evaluated. Postoperative CRP levels were analyzed for the first 14 days after surgery. The AUC on days 7 and 14 were calculated and compared with clinicopathological features and survival. The cut-off values for CRP at 7 days (CRP 7 d) and 14 days (CRP 14 d) were 599 mg/L and 1153 mg/L, respectively. Results The patients in the low CRP 7 d group had significantly better recurrence-free survival (RFS) and overall survival (OS), not that in the low CRP 14d group. The OS rates in the high CRP groups at PODs 1, 3, 10, and 14 were significantly lower than those in the low CRP groups. Postoperative complications were more common in the high CRP groups on PODs 3, 10, and 14. Univariate analyses revealed that pTNM stage, depth of tumor invasion, tumor location, lymph node involvement, and CRP 7 d were significant prognostic factors for both OS and RFS. The Cox proportional hazards model identified pTNM, tumor location, and CRP 7d as independent prognostic factors for the RFS and OS. Conclusions Early prediction of patients with postoperative complications, and adequate management will suppress the elevation of CRP 7 d and further suppress the CRP value in the late postoperative period, which may improve the prognosis of esophageal cancer patients after esophagectomy.
Published: 2024
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2. Prognostic factors for gastric cancer patients aged ≥ 85 years

Author: Shunji Endo, Masaharu Higashida, Kei Furuya, Shuya Yano, Toshimasa Okada, Kazuhiko Yoshimatsu, Yoshinori Fujiwara, and Tomio Ueno
Subjects: Aged, 85 and over, Gastrectomy, Prognosis, Stomach neoplasms, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background As gastric cancer patients aged ≥ 85 years have a short life expectancy and often die from other diseases such as pneumonia, indications for surgery are controversial. In this study, we retrospectively analyzed the prognostic factors of elderly patients with gastric cancer who are candidates for curative gastrectomy. Methods Among 114 patients aged ≥ 85 years with gastric cancer at our hospital between 2010 and 2019, prognostic factors were examined using the Cox proportional hazards model in 76 patients excluding those with cStage IVB or endoscopic submucosal dissection. We also analyzed the factors of pneumonia death. Results cStage was I/IIA/IIB/III/IVA in 37/6/14/14/5 patients, respectively. Treatment included distal gastrectomy in 28 patients, total gastrectomy in 6, local resection in 9, others in 3, and no surgery in 30. In univariate analyses of overall survival, Eastern Cooperative Oncology Group Performance Status, physiological score of Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM), Onodera’s prognostic nutritional index, cStage, and treatment were prognostic factors. In a multivariate analysis, POSSUM physiological score, cStage, treatment method {no surgery vs. distal gastrectomy: hazard ratio (HR) 5.78, 95% confidence interval (CI) 2.33–14.3}, (total gastrectomy vs. distal gastrectomy: HR 4.26, 95% CI 1.22–14.9) were independent prognostic factors. In univariate analyses of pneumonia-specific survival, treatment (total gastrectomy vs. distal gastrectomy: HR 6.98, 95% CI 1.18–41.3) was the only prognostic factor. Conclusions The prognosis of distal gastrectomy was better than that of non-surgery even in patients aged ≥ 85 years. However, total gastrectomy was considered to be avoidable due to the high rate of postoperative pneumonia death.
Published: 2024
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3. High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer

Author: Kei Furuya, Masao Nakajima, Ryouichi Tsunedomi, Yuki Nakagami, Ming Xu, Hiroto Matsui, Yukio Tokumitsu, Yoshitaro Shindo, Yusaku Watanabe, Shinobu Tomochika, Noriko Maeda, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, Shoichi Hazama, Tatsuya Ioka, Yoshinobu Hoshii, Tomio Ueno, and Hiroaki Nagano
Subjects: Biomarker, Bevacizumab, Chemotherapy, Metastatic colorectal cancer, Proteinase-3, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background To improve the prognosis of patients with metastatic colorectal cancer (mCRC), investigating predictive biomarkers of their prognosis and chemotherapeutic responsiveness is necessary. This study aimed to analyze the clinical significance of serum proteinase-3 (PRTN3) as a predictor for prognosis and chemosensitivity, especially to bevacizumab therapy, in mCRC. Methods This single-center retrospective observational study enrolled 79 patients with mCRC in our hospital and 353 patients with colorectal cancer in the TCGA database. Preoperative serum PRTN3 levels were measured using an enzyme-linked immunosorbent assay. The clinicopathological characteristics and prognosis according to serum PRTN3 levels were then evaluated. PRTN3 expression in tumor and stromal cells was evaluated immunohistochemically. The impact of PRTN3 levels on angiogenesis and bevacizumab sensitivity was evaluated using the tube formation assay. Results Serum PRTN3 levels were an independent poor prognostic factor for progression-free survival (PFS) (hazard ratio, 2.082; 95% confidence interval, 1.118-3.647; P=0.010) in patients with mCRC. Similarly, prognostic analysis with TCGA data sets showed poorer overall survival in patients with PRTN3 expression than that in patients without PRTN3 expression, especially in patients with stage IV. Immunohistochemical analysis of resected specimens revealed that stromal neutrophils expressed PRTN3, and their expression level was significantly correlated with serum PRTN3 levels. Interestingly, the effectiveness of first-line chemotherapy was significantly poorer in the high serum PRTN3 level group. High serum PRTN3 was significantly associated with poor PFS (hazard ratio, 3.027; 95% confidence interval, 1.175–7.793; P=0.0161) in patients treated with bevacizumab, an anti-angiogenic inhibitor. The tube formation assay revealed that PRTN3 administration notably augmented angiogenesis while simultaneously attenuating the anti-angiogenic influence exerted by bevacizumab therapy. Conclusions Serum PRTN3 levels could be a novel predictive biomarker of PFS of first-line chemotherapy, especially for bevacizumab therapy, in patients with mCRC
Published: 2024
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4. End Sigmoid Colostomy Reconstruction Using Purse-string Subcutaneous Suture via Extraperitoneal Route at the Site of a Previous Transperitoneal Loop Stoma

Author: Kazuhiko Yoshimatsu, Hironori Tanaka, Yoshitomo Ito, Seiya Kinoshita, Masaharu Higashida, Toshimasa Okada, Shuji Endo, Yoshinori Fujiwara, and Tomio Ueno
Subjects: stoma recreation, extraperitoneal route, a purse-string suture, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: We previously experienced two cases of end sigmoid colostomy reconstruction via the extraperitoneal route at the same site as the transperitoneal loop stoma. For an anterior rectus fascia, the transperitoneal route used closed intraperitoneal interrupted sutures and continuous sutures with barbed sutures. A new extraperitoneal route was established through the sutured anterior rectus sheath. Before reconstructing the end stoma, a subcutaneous purse-string with monofilament absorbable sutures tied to create an approximately 2.5 cm diameter was used. There were no early complications associated with the stoma. One year after surgery, a parastomal hernia was not defined. Using the presented technique, two cases were successfully recreated extraperitoneally at the same site's end stoma.
Published: 2023
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5. CD4 and FOXP3 as predictive markers for the recurrence of T3/T4a stage II colorectal cancer: applying a novel discrete Bayes decision rule

Author: Yuki Nakagami, Shoichi Hazama, Nobuaki Suzuki, Shin Yoshida, Shinobu Tomochika, Hiroto Matsui, Yoshitaro Shindo, Yukio Tokumitsu, Satoshi Matsukuma, Yusaku Watanabe, Michihisa Iida, Ryouichi Tsunedomi, Shigeru Takeda, Tomonobu Fujita, Yutaka Kawakami, Hiroyuki Ogihara, Yoshihiko Hamamoto, Tatsuya Ioka, Tsuyoshi Tanabe, Tomio Ueno, and Hiroaki Nagano
Subjects: Colorectal cancer, Discrete Bayes decision rule, Prognosis, CD4, Forkhead box P3, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background We recently reported the relapse-free survival (RFS) significance of the combination of CD4+ and forkhead box P3+ (FOXP3) T-cell densities identified by immunohistochemistry in patients with stage I, II, and III colorectal cancer (CRC) who underwent curative resections. This study was designed to determine the optimal combination of markers that predict recurrence in patients with T factors of T3/T4a stage II CRC by applying a novel Bayes decision rule. Methods Using 137 cancer tissue specimens from T3/T4a stage II patients, 12 clinicopathologic and immune factors were analysed as predictive candidates for recurrence. Results Our study showed that the combination of low CD4+ and low FOXP3+ T-cell densities resulted in extremely poor RFS. Conclusions Adjuvant chemotherapy may be considered for patients with a combination of low CD4+ and low FOXP3+ T-cell densities. The discovery of this new prognostic indicator is important for the appropriate management of patients undergoing curative resection for T3/T4a stage II CRC.
Published: 2022
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6. Subjective factors affecting prognosis of 469 patients with esophageal squamous cell carcinoma: a retrospective cohort study of endoscopic screening

Author: Jun Nakamura, Noriaki Manabe, Tomoki Yamatsuji, Yoshinori Fujiwara, Takahisa Murao, Maki Ayaki, Minoru Fujita, Akiko Shiotani, Tomio Ueno, Yasumasa Monobe, Takashi Akiyama, Ken Haruma, Yoshio Naomoto, and Jiro Hata
Subjects: Esophageal squamous cell carcinoma, Cancer screening, Prognosis, Symptoms, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Abstract Background To date, no in-depth studies have focused on the impact of various clinical characteristics of esophageal squamous cell carcinoma (ESCC), including its association with subjective symptoms, on patient prognosis. We aimed to investigate the clinical factors that affect the prognosis of patients with ESCC and to clarify how subjective symptoms are related to prognosis. Methods We retrospectively evaluated the clinical records of 503 consecutive patients with ESCC from April 2011 to December 2019. Six established prognostic factors for ESCC (body mass index, alcohol drinking, cigarette smoking, sex, clinical stage, and age) and subjective symptoms were used to subgroup patients and analyze survival differences. Next, the patients were divided into two groups: a symptomatic group and an asymptomatic group. In the symptomatic group, differences in the incidence of subjective symptoms according to tumor size, tumor location, macroscopic tumor type, and clinical stage were examined. Finally, subjective symptoms were divided into swallowing-related symptoms and other symptoms, and their prognosis was compared. Results Multivariate Cox regression analysis identified sex [hazard ratio (HR) 1.778; 95% CI 1.004–3.149; p = 0.049], TNM classification (HR 6.591; 95% CI 3.438–12.63; p
Published: 2022
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7. Prognostic factors for elderly gastric cancer patients who underwent gastrectomy

Author: Shunji Endo, Tomoki Yamatsuji, Yoshinori Fujiwara, Masaharu Higashida, Hisako Kubota, Hideo Matsumoto, Hironori Tanaka, Toshimasa Okada, Kazuhiko Yoshimatsu, Ken Sugimoto, and Tomio Ueno
Subjects: Gastric cancer, Aged, Octogenarians, Surgery, Prognostic factor, RD1-811, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Patients with gastric cancer are aging in Japan. It is not clear which patients and which surgical procedures have survival benefits after gastrectomy. A multivariate analysis was performed. Methods The medical records of 166 patients aged ≥ 80 years who underwent gastrectomy without macroscopic residual tumors were retrospectively reviewed. Univariate and multivariate analyses using Cox proportional hazard models were performed to detect prognostic factors for overall survival. Results In univariate analyses, age (≥ 90 vs. ≥ 80,
Published: 2022
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8. Inhibition of pancreatic cancer-cell growth and metastasis in vivo by a pyrazole compound characterized as a cell-migration inhibitor by an in vitro chemotaxis assay

Author: Shuichiro Okamoto, Kei Miyano, Tominari Choshi, Norihiko Sugisawa, Takashi Nishiyama, Rika Kotouge, Masahiro Yamamura, Masakiyo Sakaguchi, Rie Kinoshita, Nahoko Tomonobu, Naoki Katase, Kyo Sasaki, Sohji Nishina, Keisuke Hino, Koji Kurose, Mikio Oka, Hisako Kubota, Tomio Ueno, Toshihiro Hirai, Hideyo Fujiwara, Chikage Kawai, Masumi Itadani, Aya Morihara, Kouji Matsushima, Shiro Kanegasaki, Robert M. Hoffman, Akira Yamauchi, and Futoshi Kuribayashi
Subjects: Gemcitabine, Pyrazole, Chemotaxis, Pancreatic cancer, Therapeutics. Pharmacology, RM1-950
Abstract: Pancreatic cancer is recalcitrant to treatment as it is highly metastatic and rapidly progressive. While observing the behavior of human pancreatic BxPC-3 cells using an optical assay device called TAXIScan, we found that several synthetic pyrazole and pyrimidine derivatives inhibited cell migration. One such compound, 14–100, inhibited metastasis of fluorescence-labeled BxPC-3 cells, which were transplanted into the pancreas of nude mice as a subcutaneously grown cancer fragment. Surprisingly, despite its low cytotoxicity, the compound also showed an inhibitory effect on cancer cell proliferation in vivo, suggesting that the compound alters cancer cell characteristics needed to grow in situ. Single-cell RNA-sequencing revealed changes in gene expression associated with metastasis, angiogenesis, inflammation, and epithelial-mesenchymal transition. These data suggest that the compound 14–100 could be a good drug candidate against pancreatic cancer.
Published: 2022
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9. Successful treatment of gastric cancer after complete response of lung cancer by nivolumab: a case report

Author: Shunji Endo, Yoshinori Fujiwara, Koji Kurose, Masaharu Higashida, Hisako Kubota, Yuko Okamoto, Shumei Mineta, Hironori Tanaka, Toshimasa Okada, Atsushi Tsuruta, Takashi Akiyama, Toru Oga, and Tomio Ueno
Subjects: Stomach neoplasms, Lung neoplasms, Laparoscopic gastrectomy, Nivolumab, Surgery, RD1-811
Abstract: Abstract Background Nivolumab is effective for gastric cancer and lung cancer, but complete response is rare. We experienced a case of synchronous gastric cancer and lung cancer who was treated by nivolumab and laparoscopic gastrectomy. Case presentation A 63-year-old male consulted our institution and was found to have gastric cancer cT1(SM)N0M0 Stage IA and lung cancer cT2N2M1(PUL) Stage IV. He received eight chemotherapy treatments plus radiation, but the lung disease remained progressive. Finally, he received nivolumab therapy and complete response of both cancers was obtained. The gastric cancer recurred, but was successfully treated by laparoscopic gastrectomy. The resected specimen revealed three lesions, each being pT1aN0M0 Stage IA. The primary gastric cancer seemed to have completely vanished without scarring. Conclusions This was thought to be a rare case of gastric cancer recurrence after complete response of gastric cancer and lung cancer to nivolumab.
Published: 2020
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10. Prognostic factors for elderly gastric cancer patients who underwent gastrectomy

Author: Hisako Kubota, Tomio Ueno, Shunji Endo, Kazuhiko Yoshimatsu, Hideo Matsumoto, Masaharu Higashida, Yoshinori Fujiwara, Ken Sugimoto, Toshimasa Okada, Tomoki Yamatsuji, and Hironori Tanaka
Subjects: medicine.medical_specialty, Octogenarians, RD1-811, medicine.medical_treatment, Gastroenterology, Gastrectomy, Stomach Neoplasms, Internal medicine, medicine, Humans, RC254-282, Retrospective Studies, Aged, Prognostic factor, business.industry, Research, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, medicine.disease, Oncology, Lymph Node Excision, Surgery, business, Gastric cancer
Abstract: Background Patients with gastric cancer are aging in Japan. It is not clear which patients and which surgical procedures have survival benefits after gastrectomy. A multivariate analysis was performed. Methods The medical records of 166 patients aged ≥ 80 years who underwent gastrectomy without macroscopic residual tumors were retrospectively reviewed. Univariate and multivariate analyses using Cox proportional hazard models were performed to detect prognostic factors for overall survival. Results In univariate analyses, age (≥ 90 vs. ≥ 80, Conclusions ASA-PS was a useful predictor for postoperative mortality. Gastrectomy including cardia is best avoided.
Published: 2022

11. Perioperative Predictive Markers for Recurrence of Esophageal Cancer after Esophagectomy

Author: Masaharu Higashida, Shunji Endo, Yoshinori Fujiwara, Shumei Mineta, Hisako Kubota, Tomio Ueno, and Yuko Okamoto
Subjects: medicine.medical_specialty, Multivariate analysis, biology, Receiver operating characteristic, business.industry, medicine.medical_treatment, C-reactive protein, Pharmaceutical Science, Perioperative, Esophageal cancer, medicine.disease, Gastroenterology, Esophagectomy, Internal medicine, Propensity score matching, medicine, biology.protein, Stage (cooking), business, Research Article
Abstract: Introduction: We studied whether perioperative nutritional, immunological factors or postoperative inflammatory responses predicted esophageal cancer (EC) progression and prognosis in patients who received esophagectomies. Methods: We evaluated preoperative prognostic nutritional index (PNI), BMI, neutrophil-to-lymphocyte ratio (NLR), intraoperative blood loss, postoperative C-reactive protein (CRP) max, recurrence-free survival (RFS), and overall survival (OS) in 111 patients with pStage I–IV squamous cell EC who received esophagectomies. Optimal cutoff values for each continuous parameter were determined by receiver operating characteristic curves and Youden indices. Univariate and multivariate Cox analyses were used to derive independent prognostic factors. Propensity score matching using inverse probability of treatment weighting was used in groups divided by Youden indices, as appropriate. Results: Cutoff values of continuous variables were NLR: 2.27, PNI: 44.2, blood loss: 159 mL, and CRPmax: 21.7 mg/dL. In multivariate analyses, PNI, CRPmax, and intraoperative blood loss were independent prognostic factors for OS and RFS. Among patients with stage II–IV disease, low PNI was associated with shorter RFS. Postoperative respiratory complications were associated with both higher CRP and shorter RFS. Discussion/Conclusions: Low preoperative PNI and high postoperative inflammatory response were associated with postoperative EC progression after esophagectomy. Preoperative nutritional interventions or suppression of postoperative inflammatory response, including respiratory complications, may improve patient prognosis.
Published: 2021

12. Novel adjuvant dendritic cell therapy with transfection of heat-shock protein 70 messenger RNA for patients with hepatocellular carcinoma: a phase I/II prospective randomized controlled clinical trial

Author: Satoshi Matsukuma, Hiroto Matsui, Nobuaki Suzuki, Masao Nakajima, Shin Yoshida, Yoshitaro Shindo, Shoichi Hazama, Masaaki Oka, Shigeru Takeda, Michihisa Iida, Yukio Tokumitsu, Ming Xu, Shigefumi Yoshino, Tomio Ueno, Hiroaki Nagano, and Shinobu Tomochika
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.medical_treatment, Immunology, Cell- and Tissue-Based Therapy, Adjuvants, Immunologic, Internal medicine, medicine, Adjuvant therapy, Clinical endpoint, Humans, Immunology and Allergy, HSP70 Heat-Shock Proteins, Prospective Studies, RNA, Messenger, Adverse effect, Aged, Aged, 80 and over, business.industry, Liver Neoplasms, Dendritic Cells, Immunotherapy, Middle Aged, Prognosis, medicine.disease, Combined Modality Therapy, digestive system diseases, Survival Rate, Clinical trial, Case-Control Studies, Hepatocellular carcinoma, Immunohistochemistry, Female, Neoplasm Recurrence, Local, business, Adjuvant, Follow-Up Studies
Abstract: A proteomic analysis of hepatocellular carcinoma (HCC) has revealed that Heat Shock Protein 70 (HSP70) is among the cancer antigen proteins of HCC. Moreover, we confirmed that HSP70 was highly expressed in HCC by immunohistochemical staining. Based on these results, we developed an HSP70 mRNA-transfected dendritic cell (DC) therapy for treating unresectable or recurrent HCC, and the phase I trial was completed successfully. Thus, we aimed to investigate the safety and efficacy of this therapy as a postoperative adjuvant treatment after curative resection for HCC to prevent recurrence by conducting a phase I/II randomized controlled clinical trial. Patients (n = 45) with resectable HCC of stages II–IVa were registered and randomly assigned into two groups (DC group: 31 patients, control group: 14 patients) before surgery. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were safety and overall survival. The DC therapy was initially administered at approximately 1 week after surgery, and twice every 3–4 weeks thereafter. No adverse events specific to the immunotherapy were observed in the DC group. There was no difference in DFS between the DC and control groups (p = 0.666). However, in the subgroup with HSP70-expressing HCC, DFS of the DC group tended to be better (p = 0.090) and OS of the DC group was significantly longer (p = 0.003) than those of the control group. The HSP70 mRNA-transfected DC therapy was performed safely as an adjuvant therapy. The prognosis of HSP70-expressing HCC cases could be expected to improve with this therapy.
Published: 2020

13. Determining the protective characteristics and risk factors for the development of anastomotic leakage after low anterior resection for rectal cancer

Author: Michihisa Iida, Tomio Ueno, Yuki Nakagami, Shoichi Hazama, Nobuaki Suzuki, Yoshitaro Shindo, Hiroaki Nagano, Shinobu Tomochika, Yukio Tokumitsu, Shigeru Takeda, and Shin Yoshida
Subjects: Male, medicine.medical_specialty, Colorectal cancer, Operative Time, Blood Loss, Surgical, Pelvic inlet, Protective factor, Anastomotic Leak, Pelvis, Stoma, Postoperative Complications, Risk Factors, Colorectal surgery, Surgical oncology, medicine, Humans, Rectal cancer, Risk factor, Digestive System Surgical Procedures, Aged, Retrospective Studies, Rectal Neoplasms, business.industry, Anastomosis, Surgical, Pelvic index, Surgical Stomas, General Medicine, Middle Aged, Protective Factors, medicine.disease, Surgery, medicine.anatomical_structure, Female, Original Article, Median body, business
Abstract: Purpose Anastomotic leakage is one of the most serious postoperative complications associated with surgery for rectal cancer. The present study aimed to identify the protective characteristics and risk factors associated with anastomotic leakage after low anterior resection for rectal cancer. Methods This was a retrospective, single-center study conducted between January 2009 and December 2017 at our institution. In total, 136 rectal cancer patients who underwent low anterior resection were included in the study. We analyzed preoperative and intraoperative factors. In addition, the pelvic dimensions were measured using computed tomography in all cases. Results Among the 136 patients, anastomotic leakage occurred in 21 (15.4%), including 18 males and 3 females. The median body mass index was 21.1 kg/m2. The construction of a covering stoma was found to be a protective factor. In addition, the operation time (≥ 373 min), intraoperative blood loss (≥ 105 ml), and size of the pelvic inlet (≥ 113 mm) were identified as risk factors for anastomotic leakage. Conclusion The construction of a covering stoma was a possible protective factor. However, a longer operation time, higher intraoperative blood loss, and larger pelvic inlet dimensions were possible risk factors for developing anastomotic leakage after low anterior resection in patients with rectal cancer.
Published: 2020

14. Successful treatment of gastric cancer after complete response of lung cancer by nivolumab: a case report

Author: Yuko Okamoto, Shumei Mineta, Atsushi Tsuruta, Hironori Tanaka, Tomio Ueno, Takashi Akiyama, Toshimasa Okada, Koji Kurose, Yoshinori Fujiwara, Masaharu Higashida, Shunji Endo, Hisako Kubota, and Toru Oga
Subjects: medicine.medical_specialty, medicine.medical_treatment, Stomach neoplasms, lcsh:Surgery, Case Report, Cancer recurrence, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Lung neoplasms, Internal medicine, Medicine, 030212 general & internal medicine, Stage (cooking), Lung cancer, Complete response, Chemotherapy, business.industry, Laparoscopic gastrectomy, Cancer, lcsh:RD1-811, medicine.disease, Nivolumab, 030220 oncology & carcinogenesis, business
Abstract: Background Nivolumab is effective for gastric cancer and lung cancer, but complete response is rare. We experienced a case of synchronous gastric cancer and lung cancer who was treated by nivolumab and laparoscopic gastrectomy. Case presentation A 63-year-old male consulted our institution and was found to have gastric cancer cT1(SM)N0M0 Stage IA and lung cancer cT2N2M1(PUL) Stage IV. He received eight chemotherapy treatments plus radiation, but the lung disease remained progressive. Finally, he received nivolumab therapy and complete response of both cancers was obtained. The gastric cancer recurred, but was successfully treated by laparoscopic gastrectomy. The resected specimen revealed three lesions, each being pT1aN0M0 Stage IA. The primary gastric cancer seemed to have completely vanished without scarring. Conclusions This was thought to be a rare case of gastric cancer recurrence after complete response of gastric cancer and lung cancer to nivolumab.
Published: 2020

15. Inhibitory Effect of Eicosapentaenoic Acid on the Migration of the Esophageal Squamous Cell Carcinoma Cell Line TE-1

Author: Tomio Ueno, Hideo Matsumoto, Ayako Ogo, Toshihiro Hirai, Akira Yamauchi, and Hisako Kubota
Subjects: Cancer Research, Antineoplastic Agents, complex mixtures, Metastasis, Cell Movement, Cell Line, Tumor, medicine, Humans, Inhibitory effect, health care economics and organizations, Chemistry, Chemotaxis, Cell migration, social sciences, General Medicine, medicine.disease, Eicosapentaenoic acid, Molecular biology, Eicosapentaenoic Acid, Oncology, Cell culture, Cancer cell, lipids (amino acids, peptides, and proteins), Esophageal Squamous Cell Carcinoma, geographic locations, Fetal bovine serum
Abstract: Background/aim Eicosapentaenoic acid (EPA) inhibits NF-ĸB activation and IL-6 production in TE-1 esophageal cancer cells. NF-ĸB is related to cancer cell migration. The aim of this study is to evaluate whether EPA has a metastasis suppressing effect. Herein, we investigated EPA-treated TE-1 cell migration using TAXIScan. Materials and methods EZ-TAXIScan® was used to verify whether EPA inhibits cancer cell chemotaxis. Results Using 50% fetal bovine serum (chemoattractant) without EPA (positive control), average velocity was 0.306±0.084 μm/min compared to 0.162±0.067 μm/min without chemoattraction (negative control). Directionalities of positive and negative controls were 1.039±0.152 and 0.488±0.251 radians, respectively, indicating a significant increase in migration of the positive control compared to that of the negative control. Average velocities were 0.306±0.084 (no EPA), 0.288±0.078 (100 μM EPA), and 0.240±0.054 200 μM (EPA) μm/min, indicating that EPA reduced velocity dose-dependently. Average directionalities were 1.039±0.152 (no EPA), 0.967±0.164 (100 μM EPA), and 0.901±0.146 (200 μM EPA) radians, indicating that EPA also inhibited directionality dose-dependently. Conclusion EPA suppresses directional migration of TE-1 cells.
Published: 2020

16. Prognostic Nutritional Index as a Predictor of Postoperative Outcome in Patients Aged 85 Years or Older After Colorectal Cancer Surgery

Author: Yusaku Watanabe, Yoshinori Fujiwara, Tomio Ueno, Atsushi Tsuruta, Shumei Mineta, Hiroaki Tanioka, and Takeshi Nagasaka
Subjects: Univariate analysis, medicine.medical_specialty, Receiver operating characteristic, medicine.diagnostic_test, business.industry, Colorectal cancer, medicine.disease, Cardiac surgery, Surgery, Plastic surgery, Cardiothoracic surgery, Pediatric surgery, medicine, business, Laparoscopy
Abstract: The preoperative prognostic nutritional index (PNI) calculated based on the serum albumin concentration and peripheral blood lymphocyte count has been reported to correlate with the prognosis in patients undergoing cancer surgery. However, in case of very old patients over 85 years old, the value of preoperative PNI in colorectal cancer has not been studied in any detail. The aim of this study was to assess the PNI as a predictor of postoperative outcome in elderly patients over 85 years old with colorectal cancer. We performed a retrospective review in forty-five patients over 85 years old who underwent colorectal tumor resection at our hospital from April 2013 to March 2018. The correlations between preoperative PNI and postoperative complications were examined. The incidence rate of postoperative complications was 31.1% (14/45). All of cases with postoperative complications were improved conservatively. The median preoperative PNI was 43.20 (range 24.05–57.05) in the validation study. According to the receiver operating characteristic (ROC) curve, cutoff value of PNI was set at 45.0 in the validation study. An univariate analysis demonstrated that PNI (p = 0.0006), operation style (elective/emergency) (p = 0.03), operation approach (open/laparoscopy) (p = 0.03), and T factor (p = 0.04). A multivariate analysis showed that PNI was independent predictive factor of postoperative complications. Moreover 3-year overall survival rates of patients in the PNI ≧ 45 and PNI p = 0.009). This study suggested that PNI is a pivotal independent predictor of the postoperative outcome among elderly patients over 85 years old after colorectal cancer surgery.
Published: 2020

17. A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial

Author: Shin Yoshida, Akira Saito, Nobuaki Suzuki, Yuki Nakagami, Hiroto Matsui, Koji Tamada, Michihisa Iida, Hiroaki Nagano, Masao Nakajima, Shigefumi Yoshino, Shigeru Takeda, Toshinari Uematsu, Hideki Arima, Yasunobu Kouki, Tomio Ueno, Satoshi Matsukuma, Shinobu Tomochika, Shigeru Yamamoto, Shun Doi, Keiko Udaka, Yoshitaro Shindo, Yukio Tokumitsu, Shoichi Hazama, and Shinsuke Kanekiyo
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_treatment, HLAG-3Ig plus Poly-ICLC, Cohort Studies, 0302 clinical medicine, Poly ICLC, Immunology and Allergy, Polylysine, Neoplasm Metastasis, Gastrointestinal Neoplasms, Aged, 80 and over, biology, Middle Aged, Prognosis, Multi-HLA binding, Gastrointestinal cancers, Survival Rate, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Female, Peptide vaccination therapy, Antibody, Adjuvant, medicine.drug, Adult, T cell, Immunology, Human leukocyte antigen, Glypican 3, 03 medical and health sciences, Immune system, Adjuvants, Immunologic, Glypicans, TIGIT, medicine, Humans, HSP70 Heat-Shock Proteins, Neoplasm Invasiveness, Aged, HLA-G Antigens, HLA-A Antigens, business.industry, Peptide Fragments, Poly I-C, 030104 developmental biology, Clinical Trial Report, Carboxymethylcellulose Sodium, Cancer research, biology.protein, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract: Background This phase I study aimed to evaluate the safety, peptide-specific immune responses, and anti-tumor effects of a novel vaccination therapy comprising multi-HLA-binding heat shock protein (HSP) 70/glypican-3 (GPC3) peptides and a novel adjuvant combination of hLAG-3Ig and Poly-ICLC against metastatic gastrointestinal cancers. Methods HSP70/GPC3 peptides with high binding affinities for three HLA types (A*24:02, A*02:01, and A*02:06) were identified with our peptide prediction system. The peptides were intradermally administered with combined adjuvants on a weekly basis. This study was a phase I dose escalation clinical trial, which was carried out in a three patients’ cohort; in total, 11 patients were enrolled for the recommended dose. Results Seventeen patients received this vaccination therapy without dose-limiting toxicity. All treatment-related adverse events were of grades 1 to 2. Peptide-specific CTL induction by HSP70 and GPC3 proteins was observed in 11 (64.7%) and 13 (76.5%) cases, respectively, regardless of the HLA type. Serum tumor marker levels were decreased in 10 cases (58.8%). Immunological analysis using PBMCs indicated that patients receiving dose level 3 presented with significantly reduced T cell immunoglobulin and mucin-domain containing-3 (TIM3)-expressing CD4 + T cells after one course of treatment. PD-1 or TIM3-expressing CD4 + T cells and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT)-expressing CD8 + T cells in PBMCs before vaccination were negative predictive factors for survival. Conclusions This novel peptide vaccination therapy was safe for patients with metastatic gastrointestinal cancers.
Published: 2020

18. Preoperative Inflammatory Response to Esophageal Cancer Is More Reliable Prognostic Factor in Patients Received Esophagectomy

Author: Yoshinori Fujiwara, Shunji Endo, Masaharu Higashida, Hisako Kubota, Seiya Kinoshita, Kazuhiko Yoshimatsu, and Tomio Ueno
Abstract: Background: Inflammation and nutrition are closely related to the progression of gastrointestinal malignancies. We aimed to explore the potential of preoperative inflammation-based or nutrition-based biomarkers as predictors of survival in patients with resectable esophageal squamous cell carcinoma (ESCC) using multivariate Cox analysis.Methods: We included 122 patients with resectable ESCC (stages I–IV) in the study. We assessed the inflammation-based modified Glasgow prognostic score (mGPS), nutrition-based modified controlling nutritional status (mCONUT) score, CRP(C-reactive protein),serum albumin, lymphocyte counts, and total cholesterol. The relationships of these biomarkers with overall survival (OS) and recurrence-free survival (RFS) were evaluated. Three Cox model were performed for single parameters(CRP, albumin, lymphocyte, total cholesterol), for mCONUT and mGPS,and for clinicopathological factors.Results: The cut-off values for CRP, albumin, and mCONUT measured using receiver operating characteristic (ROC) curves were 0.3, 3.5, and 4, respectively. Patients with high mGPS and high mCONUT scores were significantly associated with shorter OS and RFS (p < 0.05).Multivariate Cox analysis showed that mGPS,pStage,tumor location were independent prognostic factors both FRS and OS. Also, Cox analysis for single parameters showed that preoperative CRP, lymphocyte counts were independent prognostic factors for RFS and albumin was prognostic factor for OS.Conclusions: Preoperative inflammation-based mGPS is most reliable independent prognostic factor in patients with resectable ESCC. Suppression of preoperative inflammation can be improved nutritional status and may improve the prognosis in these patients.
Published: 2021

19. 343 EFFECTS OF PREOPERATIVE PNI (PROGNOSTIC NUTRITIONAL INDEX) AND POSTOPERATIVE INFLAMMATORY RESPONSE ON PROGNOSIS IN PATIENTS WITH ESOPHAGEAL CANCER

Author: Masaharu Higashida, Syumei Mineta, Atsushi Tsuruta, Toshimasa Okada, Yoshinori Fujiwara, Yuko Okamoto, Hisako Kubota, and Tomio Ueno
Subjects: medicine.medical_specialty, Index (economics), business.industry, Inflammatory response, Internal medicine, Gastroenterology, medicine, In patient, General Medicine, Esophageal cancer, business, medicine.disease
Abstract: The effects of preoperative nutritional status and postoperative inflammatory response on esophageal cancer patients on prognosis were unclear. In the present study, we evaluated the preoperative nutritional parameters and postoperative inflammatory responses and analyzed relationship between these parameters and cancer prognosis. Methods One hundred and eleven esophageal squamous cell carcinoma patients were analyzed with pathological TNM StageI-IV. Preoperative nutritional parameters: PNI (Prognostic Nutritional Index) was calculated from following formula:10 x Albumin(g/dl) +0.005 x peripheral lymphocyte counts (/mm3). Preoperative NLR (Neutrophil/Lymphocyte ratio) was defined as absolute neutrophil counts divided by the absolute lymphocyte counts. The highest CRP level was evaluated as postoperative inflammatory responses. Cut-off values of these continuous parameters were calculated by ROC, and univariate and multivariate analysis using Cox model for overall survival (OS) were examined in the parameters. Results Overall three or five years survivals were 60.9%, 56.28%, respectively. Cut-off value of PNI, CRP, NLR, Intraoperative blood loss were 44.8, 21.7 mg/dl,2.27,159 mL, respectively. High PNI group was significantly better survival than low group (3 years OS, 65.94 vs 45.82%, p Conclusion Preoperative nutritional status affected the prognosis of esophageal cancer patients. But, postoperative inflammatory response was not affected the prognosis of these patients. Preoperative nutritional interventions may improve the prognosis of patients with esophageal cancer.
Published: 2021

20. Intratumoural-infiltrating CD4 + and FOXP3 + T cells as strong positive predictive markers for the prognosis of resectable colorectal cancer

Author: Yuki Nakagami, Hiroto Matsui, Tomio Ueno, Nobuaki Suzuki, Yutaka Kawakami, Naoko Okayama, Yutaka Suehiro, Yukio Tokumitsu, Ryouichi Tsunedomi, Shinsuke Kanekiyo, Shigefumi Yoshino, Shinobu Tomochika, Shin Yoshida, Tomonobu Fujita, Shigeru Takeda, Taichi Kuwahara, Michihisa Iida, Yoshitaro Shindo, Takahiro Yamasaki, Shoichi Hazama, and Hiroaki Nagano
Subjects: Cancer Research, medicine.medical_specialty, Chemotherapy, Lymphovascular invasion, business.industry, Colorectal cancer, Patient demographics, medicine.medical_treatment, Microsatellite instability, FOXP3, medicine.disease, Gastroenterology, Article, Colon cancer, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, medicine, Tumour immunology, T-stage, Immunohistochemistry, business
Abstract: Background CD3 + and CD8 + T-cell infiltration were reported as positive predictive markers of survival in colorectal cancer (CRC) patients. Here, we demonstrate the prognostic significance of CD4 + and FOXP3 + T-cell densities in CRC. Methods We quantified the intratumoural densities of CD3 + , CD8 + , CD4 + and FOXP3 + T cells by immunohistochemistry and digital pathology in 342 CRC patients who underwent curative resection. Microsatellite instability was also assessed in 322 specimens. Patient demographics, clinicopathological features and survival rates were analysed. Results High CD3 + , CD4 + and FOXP3 + T-cell densities were associated with improved relapse-free survival (RFS); high CD8 + , CD4 + and FOXP3 + T-cell densities were associated with improved disease-specific survival (DSS). Patients with low CD4 + and low FOXP3 + T-cell densities exhibited extremely poor prognoses. T stage, vascular/lymphatic invasion and CD4 + T-cell density were independent prognostic indicators for DSS. The distributions of CD4 + and FOXP3 + T-cell densities were not significantly different between the high microsatellite instability group and other groups, in contrast to those of CD3 + and CD8 + T-cell densities. Conclusions Intratumoural CD4 + T-cell density and combined CD4 + and FOXP3 + T-cell densities were stronger prognostic indicators than other clinicopathological features. These results may facilitate the establishment of novel prognostic factors and therapeutic strategies for CRC.
Published: 2019

21. The Mechanism of the Synergistic Anticancer Effect of CDDP and EPA in the TE1 Cell Line

Author: Ayako Ogo, Masaharu Higashida, Hideo Matsumoto, Hisako Kubota, Toshihiro Hirai, Tomio Ueno, Fusako Teramoto, and Sachi Miyake
Subjects: inorganic chemicals, Cancer Research, Cell cycle checkpoint, Esophageal Neoplasms, medicine.medical_treatment, Apoptosis, Flow cytometry, Cell Line, Tumor, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, neoplasms, health care economics and organizations, Unsaturated fatty acid, Cisplatin, medicine.diagnostic_test, Chemistry, Interleukin-6, NF-kappa B, Drug Synergism, General Medicine, Cell cycle, Eicosapentaenoic acid, female genital diseases and pregnancy complications, G2 Phase Cell Cycle Checkpoints, Cytokine, Oncology, Eicosapentaenoic Acid, S Phase Cell Cycle Checkpoints, Cancer research, lipids (amino acids, peptides, and proteins), medicine.drug, Signal Transduction
Abstract: Background/aim Eicosapentaenoic acid (EPA) is an unsaturated fatty acid with various bioactivities, including antitumor effects. We previously reported a synergistic antitumor effect of cisplatin (CDDP) and EPA. Here, we examined the underlying mechanism. Materials and methods The human oesophageal cancer cell line TE-1 was treated with the combination of EPA and CDDP. Nuclear translocation of NF-κB, a transcription factor involved in cytokine production, was detected by immunohistochemistry. IL-6 levels were measured by ELISA. Apoptosis and cell cycle distribution were evaluated by flow cytometry. Results Nuclear translocation of NF-κB in TE-1 cells was synergistically decreased by CDDP and EPA. IL-6 production was increased following treatment with CDDP, but treatment with EPA decreased IL-6 levels. Apoptosis was synergistically induced by CDDP and EPA. A G2/M cell cycle arrest was observed with the combination of CDDP and 150 μM EPA, and S phase arrest with the combination of CDDP and 100 μM EPA. Conclusion The combination of CDDP and EPA synergistically suppresses NF-κB nuclear translocation and increases apoptosis by inducing cell cycle arrest at the S or G2/M phase.
Published: 2021

22. Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study

Author: Dmitri, Nepogodiev, Joana Ff Simoes, Elizabeth, Li, Maria, Picciochi, James, C Glasbey, Glauco, Baiocchi, Ruth, Blanco-Colino, Daoud, Chaudhry, Ehab, Alameer, Kariem, El-Boghdadly, Funmilola, Wuraola, Dhruva, Ghosh, Rohan, R Gujjuri, Ewen, M Harrison, Herman, Lule, Haytham, Kaafarani, Mohammad, Khosravi, Irmgard, Kronberger, Sezai, Leventoğlu, Harvinder, Mann, Kenneth, A Mclean, Mengistu Gebreyohanes Mengesha, Maria Marta Modolo, Faustin, Ntirenganya, Lisa, Norman, Oumaima, Outani, Riinu, Pius, Peter, Pockney, Ahmad Uzair Qureshi, April Camilla Roslani, Sohei, Satoi, Catherine, Shaw, Aneel, Bhangu, Omar, M Omar, Waheed-Ul-Rahman, Ahmed, Leah, Argus, Alasdair, Ball, Edward, P Bywater, Amanpreet, Brar, Brett, E Dawson, Irani, Duran, Muhammed, Elhadi, Conor, S Jones, Sivesh, K Kamarajah, James, M Keatley, Samuel, Lawday, Ella, J Marson, Riinu, Ots, Irène, Santos, Elliott, H Taylor, Isobel, M Trout, Chris, Varghese, Mary, L Venn, William, Xu, Irida, Dajti, Arben, Gjata, Salah Eddine Oussama Kacimi, Luis, Boccalatte, Daniel, Cox, Philip, Townend, Felix, Aigner, Irmgard Elisabeth Kronberger, Elgun, Samadov, Amer, Alderazi, Kamral, Hossain, Greg, Padmore, Gabrielle van Ramshorst, Ismaïl, Lawani, Anis, Cerovac, Samir, Delibegovic, Gustavo Mendonça Ataíde Gomes, Igor Lima Buarque, Muhammad, Gohar, Mihail, Slavchev, Chukwuemeka, Nwegbu, Arnav, Agarwal, Janet, Martin, Joshua, Ng-Kamstra, Maricarmen, Olivos, Wenhui, Lou, Dong-Lin, Ren, Jose Andres Calvache, Carlos, J Perez Rivera, Ana Danic Hadzibegovic, Tomislav, Kopjar, Jakov, Mihanovic, Pablo Mijahil Avilés Jiménez, Nikolaos, Gouvas, Jaroslav, Klat, René, Novysedlák, Nicolas, Amisi, Peter, Christensen, Alaa, El-Hussuna, Sylvia, Batista, Eddy, Lincango-Naranjo, Sameh, Emile, Danilo Alfonso Arévalo Sandoval, Hailu, Dhufera, Samuel, Hailu, Mengistu, G Mengesha, Joonas, H Kauppila, Alexis, P Arnaud, Zaza, Demetrashvili, Markus, Albertsmeier, Hans, Lederhuber, Markus, W Löffler, Daniel Kwesi Acquah, Bernard, Ofori, Stephen, Tabiri, Symeon, Metallidis, Georgios, Tsoulfas, Maria-Lorena, Aguilera-Arevalo, Gustavo, Recinos, Tamás, Mersich, Dániel, Wettstein, Gabriele, Kembuan, Peiman Brouki Milan, Mohammad Hossein Khosravi, Masoud, Mozafari, Ahmed, Hilmi, Helen, Mohan, Oded, Zmora, Gaetano, Gallo, Francesco, Pata, Gianluca, Pellino, Yuki, Fujimoto, Naoto, Kuroda, Mohamad, K Abou Chaar, Faris, Ayasra, Ildar, Fakhradiyev, Intisar Hisham Said Hamdun, Jang, Jin-Young, Mohammad, Jamal, Lina, Karout, Aiste, Gulla, Fanjandrainy, Rasoaherinomenjanahary, Luc Hervé Samison, Iran Irani Durán Sánchez, Diana Samantha Gonzalez, Laura, Martinez, María José Martínez, Alejandra, Nayen, Antonio Ramos-De la Medina, Jade, Nunez, Pueya Rashid Nashidengo, Rakesh, Shah, Ashish Lal Shrestha, Pascal, Jonker, Schelto, Kruijff, Milou, Noltes, Pieter, Steinkamp, Deborah, Wright, Lukman, Abdur-Rahman, Adesoji, Ademuyiwa, Adewale, Adisa, Babatunde, Osinaike, Justina, Seyi-Olajide, Omolara, Williams, Emmanuel, Williams, Sofija, Pejkova, Zainab Al Balushi, Raza, Sayyed, Mustafa Abo Mohsen, Sadi, A Abukhalaf, Moises, Cukier, Hugo, Gomez-Fernandez, Sebastian Shu Yip, Ximena Paola Vasquez Ojeda, Marie Dione Sacdalan, Piotr, Major, José, Azevedo, Miguel, F Cunha, Ahmad, Zarour, Eduard-Alexandru, Bonci, Ionut, Negoi, Sergey, Efetov, Viktor, Kochetkov, Andrey, Litvin, Jc Allen Ingabire, Georges, Bucyibaruta, Ntirenganya, Faustin, Sosthene, Habumuremyi, Alphonsine, Imanishimwe, Haragirimana Jean de Dieu, Emmanuel, Munyaneza, Isaie, Ncogoza, Abdourahmane, Ndong, Dejan, Radenkovic, Min Hoe Chew, Frederick, Koh, James, Ngu, Arpád, Panyko, Uros, Bele, Jurij Aleš Košir, Hassan, Daoud, Ana Maria Minaya Bravo, Umesh, Jayarajah, Dakshitha, Wickramasinghe, Mohammed Elmujtba Adam Essa Adam, Martin, Rutegård, Malin, Sund, Michel, Adamina, Eleftherios, Gialamas, Karoline, Horisberger, Muhammad, Alshaar, Abel, Huang, Varut, Lohsiriwat, Shane, Charles, Haithem, Jlassi, Arda, Isik, Hervé Monka Lekuya, Slava, Kopetskyi, Hayder, Alsaadi, Sattar, Alshryda, Osaid, Alser, Brittany, Bankhead-Kendall, Kerry, Breen, Hassan, Mashbari, Fernando Bonilla Cal, Hamza, Al-Naggar, Mayaba, Maimbo, Dennis, Mazingi, Tom, Abbott, Melika, Akhbari, Ruth, Benson, Shivam, Bhanderi, Bruce, Biccard, Edward, Caruana, Sohini, Chakrabortee, Reema, Chapatwala, Ainhoa, Costas-Chavarri, Andreas, K Demetriades, Anant, Desai, Salomone Di Saverio, Thomas, Drake, John, Edwards, Jonathan, Evans, Marco, Fiore, Samuel, Ford, Christina, Fotopoulou, Alexander, Fowler, Kaori, Futaba, Ian, Ganly, Harelimana Grace James, Ewen, Griffiths, Alessandro, Gronchi, Peter, Hutchinson, Gabriella Yael Hyman, Joseph, Incorvia, Ritu, Jain, Michael, Jenkinson, Tabassum, Khan, Stephen Richard Knight, Angelos, Kolias, Søren, Kudsk-Iversen, Tsun Yu Kwan, Elaine, Leung, Julio, Mayol, Siobhan, Mckay, John, G Meara, Emily, Mills, Susan, Moug, Akshay, Patel, Roberto, Perinotti, Henry, E Rice, Keith, Roberts, Andrew, Schache, Richard, Shaw, Neil, Smart, Matthew, Stephens, Grant, D Stewart, Ella, Teasdale, Peter, Vaughan-Shaw, Raghavan, Vidya, Naomi, Wright, Natalie, Zimmelman, Ervis, Agastra, Dariel, Thereska, Sergio Martin Lucchini, Veronica, Laudani, Carina, Chwat, Ivana Ines Pedraza Salazar, Diana Alejandra Pantoja Pachajoa, Agustin, Duro, José Alfredo Calderón Arancibia, Giuliana, D'Aulerio, Nagendra, Dudi-Venkata, Natasha, Egoroff, Shebani, Farik, Natalie, Lott, Jana-Lee, Moss, Sarah, Rennie, Lorwai, Tan, Uyen Giao Vo, David, Watson, David, Watters, Tim, Bright, Paul, Hollington, Xuanyu, Zhou, Hidde, M Kroon, Anthony, Farfus, John, Barker, Eleanor, Watson, Sean, Stevens, Haider, Latif, Amanda Caroline Dawson, Alwin, Chuan, Vijayaragavan, Muralidharan, Enoch, Wong, Travis, Ackermann, Maurizio, Pacilli, Russell, Hodgson, Alexander, Heriot, Peter, Choong, Wendy, Brown, Surjit, Lidder, Justin, Yeung, Luke, Traeger, Guillermo, Regalo, Ralph, Gourlay, Sarit, Badiani, Cherry, Koh, Soni, Putnis, Fayza, Haider, Ashrarur Rahman Mitul, Niels, Komen, Bert, Dhondt, Serge, Cappeliez, Manon, Pigeolet, Martijn, Schoneveld, Jasper, Stijns, Wouter, Oosterlinck, Nicolas, Flamey, Cyrille, Kpangon, Mouhamed, Agbadebo, Sèmèvo Romaric Tobome, Aldo Vieira Barros, Samuel Aguiar Júnior, Heloisa Galvão do Amaral Campos, Jefferson, Gross, Felipe José Fernandez Coimbra, Luiz Paulo Kowalski, Fabiana, Makdissi, Suely, Nakagawa, Joao Pedreira Duprat Neto, Jose Guilherme Vartanian, Guilherme, Yazbek, Stenio, C Zequi, Ronald, Flumignan, Natalia, Jaworska, Angela, Dell, Harsha, Shanthanna, Abdollah, Behzadi, Carolyn, Nessim, Michelle, Mozel, Pascal, St-Germain, Crispin, Russell, Gary, Groot, Najib, Safieddine, Duminda, Wijeysundera, Antoine, Eskander, Sami, Chadi, Shawn, Mackenzie, Alana, Flexman, Fernando, Heredia, Julio, Villanueva, Sofia, Waissbluth, Roberto, Macchiavello, Mario, I Escudero, Tyare, Fuentes, Ximena, Mimica, Dinimo Bolivar Saenz, Lina, Caicedo, Juan Pablo Alzate, Joaquin, Luna, Nestor Fabian Pedraza Alonso, Camilo Ortiz Silva, Juliana, Rodriguez, Liliana, Silva-Igua, Martha Luz Torres, Lina María Trujillo, Albaro José Nieto Calvache, Julián, Balanta-Melo, Rafael, Figueroa-Casanova, Oscar-Julián, García-Montoya, Carlos Andres Marulanda Toro, Marcela Velez Botero, Maria Clara Mendoza Arango, Eneida Diaz Martinez, Valentina Gutiérrez Perdomo, Emileth, Montenegro, Julia, Rodriguez-Abreu, Dolores, Mejía, Galal, Abouelnagah, Sameh, Shehata, Ahmed Hossam Eldin Fouad Rida, Ramy, A Hassan, Mahmoud, M Saad, Mohamed Reda Loaloa, Badr, Mostafa, Mohamed, Qassem, Mohamed, Fahmy, Hesham, Abozied, Ahmed, Y Azzam, Sherief, Ghozy, Asser, Sallam, Ahmed, Shehta, Mohamed, Abdelkhalek, Rehab, Samaka, Amr, Morsy, Ahmed Elshawadfy Sherif, Abraham, Negussie, Tigist, Fisseha, Kibruyisfaw, Shumbash, Metasebia, Abebe, Seid Mohammed Yasin, Yemisirach Bizuneh Akililu, Abebe, Megersa, Teshome, Tefera, Melatework, Assefa, Bahru, Atnafu, Bereket, Tsegaye, Yoseph Solomon Bezabih, Silamlak, Sisay, Kebebe, Bekele, Moa, Jira, Habtamu, Derilo, Eyueal, Degefa, Anteneh, Tadesse, Melkamu, Nidaw, Elise, Sarjanoja, Sylvie, Testelin, Sophie, Boucher, Lionel, Jouffret, Zaher, Lakkis, Alban Zarzavadjian Le Bian, Luke, Harper, Marc Danguy des Déserts, Benoît, André, Karem, Slim, Romain, Verhaeghe, Andrea, Police, Edouard, Girard, Alexandre, Chebaro, Armande Subayi Nkembi, Laurent, Arnalsteen, Quentin, Ballouhey, Diane, Mege, Clement, Jeandel, Emilie, Duchalais, Pierre-Alban, Bouche, Gilles, Manceau, Célia, Crétolle, Erik, Hervieux, Noémie, Girard, Agathe, Seguin-Givelet, Sebastien, Gaujoux, Belinda De Simone, Matthieu, Boisson, Damien, Bergeat, Fabien, Fredon, Francesco, Nappi, Radwan, Kassir, Aurélien, Scalabre, Federico, Migliorelli, Anne-Cecile, Ezanno, Barbara, Seeliger, Charlotte, Vaysse, Helene, Charbonneau, Vincent, Misrai, Olivier, Abbo, Martina Aida Angeles, Laurent, Brunaud, Ali, Modabber, Sebastian, Wolf, Carsten, Kamphues, Philipp, Höhn, Tim, R Glowka, Alexander Christopher Rokohl, Ulrich, Bork, Georg, Fluegen, Raymund, E Horch, Andrea, Schmedding, Andreas, Schnitzbauer, Helge, Eberbach, Daniel, Schlager, Fritz, Spelsberg, Lena, Keppler, Andreas, Hecker, Susanne, Wolfer, Ulrich, Ronellenfitsch, Christine, Nitschke, Christian, Peiper, Ibrahim, Hakami, Stefan, Welter, Karine, Nikolaieva, Andreas, Roth, Judith, Lindert, Konstantinos, Gousias, Anke, Rissmann, Valerie Catherine Linz, Nuh, Rahbari, Marie-Claire, Rassweiler-Seyfried, Anna Eleonora Gut, Jens, Gempt, Daniel, Reim, Arthur, Wagner, Alexander, M Keppler, Mircea Gabriel Stoleriu, Tim, Saier, Josef, Stadler, Julia Christina Kaiser, Stefan, M Brunner, Karin, Pfister, Jonas, Herzberg, Kai, Nowak, Tobias, Reinhard, Gregor, A Stavrou, Alfred, Königsrainer, Christian, Konrads, Markus, Quante, Simon, Laban, Silke von Pusch, Markus, Hirschburger, Johannes, Doerner, Armin, Wiegering, Ekaterini Christina Tampaki, Alitza Gutiérrez Ruiz, Alejandra, Rodas, Ana Lucía Portilla, Jacqueline, Carrera, Amalia Barrios Duarte, Megan, Lowey, Sabrina, Barillas, Atul, Suroy, Dhaivat, Vaishnav, Raghunandan Gorantlu Chowdappa, Irappa, Madabhavi, Dhananjaya, Bhat, Sunil Kumar Venkatappa, Sumit, Thakar, Kavitha, Jain, Aruna, Kumar, Manoj, Nagar, Tushar, Mishra, Arunkumar, Sekar, Anand, Gupta, Lileswar, Kaman, Madhivanan, Karthigeyan, Manjul, Tripathi, Ashwin, Rammohan, Sudheer Othiyil Vayoth, Anupama, Rajanbabu, Anbukkani, Subbian, Rahul, Gupta, Monish, Raut, Nissi, Evelyn, R Lavanya Kannaiyan, Anil, Matai, Sanjeev, Misra, Vishal, Bhende, Sathish, Muthu, Indranil, Ghosh, Abhishek, Sharma, Ankur, Bajaj, Shiv, Rajan, Gaurav, Agarwal, Pranay, Pawar, Philip, Alexander, M Vijayakumar Vijayakumar, Zeeshan, Hameed, Badareesh, L, Navneet Kumar Chaudhry, Lipika, Baliarsing, Satish, Dharap, Amruta, Kulkarni, Yuvaraja, Thyavihally, Rahul Deo Sharma, S Pramesh, C, Rajesh, Soni, Surya Kumar Dube, Shilpa, Sharma, Harvinder, Singh, Lovenish, Bains, Rahul, Ghodke, Ashwani, Kumar, Vivek, Sodhai, Suvendu, Maji, Somprakas, Basu, Chandrashekhar, Mahakalkar, Ravi, Kannan, Asif, Mehraj, Ranganath, N, Ashish, Phadnis, Yadev, I, Alfie, Kavalakat, Rohin, Mittal, Karthik Chandra Vallam, Hamed, Akhavizadegan, Esmaeil Rezghi Maleki, Naser Yousefzadeh Kandevani, Hilary, Ikele, Catherine, Mcnestry, Christina, Fleming, Stephen, O'Brien, Sami Abd Elwahab, Niall, Davis, Mohsen, Javadpour, Brendan, Mcdonnell, Clare, O Connor, Jarlath, Bolger, Cillian, Clancy, Stefanie, M Croghan, Noel, Donlon, Carolyn, Cullinane, Ben, Creavin, Muheilan, Muheilan, Helen, Earley, Syed Mohammad Umar Kabir, Muhammad, Fahadullah, Éanna, Ryan, Tara, Connelly, Daisuke, Hashimoto, Majdi Ali Alqudah, Amer, Alajalen, Rand, Y Omari, Abdulrahman, Qasem, Yazan, Alawneh, Amer, Ahmad, Omar, Aladawi, Bourhan, Alrayes, Hanan, Haidar, Shatha, Husain, Faisal, Qassem, Adnan, Sumadi, Ala'a Abu Salhiyeh, Balqees Mahmoud Al-Manaseer, Zaid, Alsunna, Hazim, Ra'Ed, Faten Reyad Bani Hamad, Amro, Abuleil, Elmi Ahmed Mohamed Jimaale, Marah, Abu-Mehsen, Noor, Olaywah, Omar, Wafi, Hazim, Ababneh, Luai, Abu-Ismail, Almu'Atasim, Khamees, Ahmad, Alkhatib, Raikhan, Bolatbekova, Mukhtar, Kulimbet, Talgat, Nurgozhin, Timur, Saliev, Baurzhan, Zhussupov, Ydyrys, Almabayev, Dilyara, Kaidarova, Khalil, Tamoos, Ahmed, Aqeelah, Alsnosy Abdullah Khalefa Mohammed, Faraj Al Maadany, Ghadah, Alkadeeki, Milad, Gahwagi, Wafa, Aldressi, Mohamed, Amnaina, Arowa Hassan Abdulrahman Alansari, Akram, Alkaseek, Ghozlan, Yagoub, Anass Ben Amer, Marwa, Salem, Ayman, Almugaddami, Dania, Burgan, Mohammed, Abdelkabir, Khayriyah, Alshareef, Rayet Al Islam Ben Jouira, Ayman, Meelad, Ahmad, Bouhuwaish, Sumayya Essayah Dwaga, Houda, Khalifa, Bushray, Almiqlash, Taha, Suliaman, Mohammed, Alawami, Fras, Elhajdawe, Hajir, Aboazamazem, Ibrahim, Ellojli, Ahmed, Msherghi, Ismail Ali Saleh, Mohammed, Alayan, Marcel Didier Ndayishyigikiye, Akutu, Munyika, Philipp, Plarre, David, W Borowski, Cameron, Wells, Rebecca, Teague, Brodie, Elliott, David, Kieser, Omar, Mohyieldin, Nick, Mcintosh, Cheyaanthan, Haran, Jasmin, King, Jeong, Ha, Matthew James McGuinness, Opeoluwa, Adesanya, Julius, Olaogun, Akinola, Akinmade, Kefas, Bwala, Peter, Agbonrofo, Akinwale, Afolabi, Usang, Usang, Sebastian, Ekenze, Samson, Olori, Taiwo Akeem Lawal, Abiodun, Okunlola, Stephen, Kache, Danjuma, Sale, Lofty-John, Anyanwu, Chukwuma, Okereke, Musliu Adetola Tolani, Venko, Filipce, Lazar, Todorovic, Sotir, Stavridis, John George Massoud, Sareyah, Alsibai, Rizwan, Sultan, Humera Naz Altaf, Abu Bakar Hafeez Bhatti, Shahzad Hussain Waqar, Aliya, Aziz, Asad Ali Kerawala, Lajpat, Rai, Mariyah, Anwer, Aiman, Tariq, Bushra, Ayub, Sami Ullah Niazi, Muhammad Yasir Naseem, Muhammad Zeeshan Sarwar, Muhammad Imran Khokhar, Imdad Ahmad Zahid, Haroon Javaid Majid, Nabila, Talat, Muhammad, Asif, Muhammad Hamid Chaudhary, Umer, Farooq, Siddique, Ahmad, Waleed, Mabood, Syed Imran Bukhari, Muhammad, Tariq, Eesha, Yaqoob, Saad, Javed, Muhammad Usman Malik, Hassan Nawaz Yaqoob, Glenda Marina Falcon Pacheco, Robinson Mas Melendez, Arazzelly Del Pilar Paucar 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Michael, Grechenig, Ricarda, Gruber, Jörg, Hutter, Tarkan, Jäger, Oliver, Koch, Michael, Lechner, Lisa, Manzenreiter, Franz, Mayer, Iris, Muehlbacher, Jaroslav, Presl, Daniel, Rezaie, Philipp, Schredl, Martin, Varga, Michael, Weitzendorfer, Angela, Wimmer, Eberhard, Brunner, Michael de Cillia, Michaela, Gruber, Martin, Grünbart, Elmar, Heinrich, Hannes, Hoi, Vanessa, Kemmetinger, Christof, Mittermair, Victoria, Mosshammer, Christian, Obrist, Peter, Paal, Judith, Roesch, Elisabeth, Russe, Tobias, Schaetz, Jan, Schirnhofer, Karl, Schwaiger, Gottfried, Wechselberger, Helmut, Weiss, Maximilian, Lanner, Alf-Dorian, Binder, Thomas, Gürtler, Marcus, Fink, Daniel, Reichhold, Radoslava, Stoyanova, Klara, Beitl, Martin, H Bernardi, Philip, Datler, Christopher, Dawoud, Alex, Farr, Philipp, Foessleitner, Christoph, Grimm, Felix, Harpain, Mir Alireza Hoda, Simone, Holawe, Marlene, Kranawetter, Johannes, Ott, Alexandra, Perricos, Maximilian, Pesta, Robert, Pillerstorff, Christian, Reiterer, Stefan, 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Mohammed Shadrul Alam, Akm Khairul Basher, Shahnoor, Islam, M Nazmul Islam, S, Sabbir, Karim, Muntasir, Faisel, Sadia, Khan, Iftekhar Ibne Mannan, Nawshin, Nazia, Malissa, Bentham, Sasha, Corbin, Alex, Doyle, Asha, Eastmond, Amelia, Haynes, Margaret, O'Shea, Emil, Phillips, Keisha, Walkes, Evgeniy, L Artyushkov, Mark, L Kaplan, Vladislav, Straltsov, Yauheniya, Litvina, Alexei, Lyzikov, Victor, E Tihmanovich, Mafalda, Borges, Tim, Brits, Nicolas De Hous, Stefan De Wachter, Tomas, Menovsky, Xavier, Mortiers, Dorien, Vermeulen, Nils, Vleminckx, Dirk, Ysebaert, Julie, Bontinck, Danny, Bulthé, Ricky, Rasschaert, Anne-Sophie Van Haver, Koen Van Belle, Laurence, Verstraeten, Manon, Vounckx, Sébastien, D'Ulisse, Yasmine De Bruyne, Badih El Nakadi, Tessely, Heloise, Matteo, Luisetto, Sotirios, Marinakis, Maxime, Maton, Claire, Viste, Elke Van Daele, Mathieu, Vandeputte, Marc, Duinslaeger, Daniel, Jacobs-Tulleneers-Thevissen, Yanina, Jansen, Ward, Janssens, Rastislav, Kunda, Nouredin, Messaoudi, Michael, Ruyssers, Ellen Van Eetvelde, Marian, Vanhoeij, Jef Van den Eynde, Raf Van den Eynde, Ahmed, M Chaoui, Marcellin, Akpla, Souliath, Lawani, Hermann, Agossou, Hulrich Aouagbe Behanzin, Covalic, Bokossa, Hubert, Dewanon, Hugues, Yome, Alassan, Boukari, Oswald, Gbehade, Labissi Francois Amossou, Francis, Dossou, Tatjana, Barišić, Miran, Boras, Zdrinko, Brekalo, Ivana Čuljak Blagojević, Ana, Damjanović, Vedran, Dragisic, Ana Dugandžić Šimić, Filip, Gunaric, Martin, Kajic, Darko, Knežević, Tanja, Krešić, Valentina, Lasić, Ludvig, Letica, Vlatka, Martinovic, Iva, Mikulic, Josip, Miskovic, Hrvoje, Pehar, Pejana, Rastović, Irena, Sesar, Violeta, Šetka-Čuljak, Martina, Soljic, Dejan, Tiric, Vajdana, Tomić, Anja, Vasilj, Igor, Hudic, Renato Aguera Oliver, Felipe Azenha Lamonica, Jorge De Medeiros, Henrique Donizetti Bianchi Florindo, Rodolfo Jose Favaretto Filho, Fernanda Costa Pereira, Rodrigo, Rodrigues, Antonio Antunes Rodrigues Junior, Fernanda Ruiz de Andrade, Maisa, Salvetti, Débora Schalge Campioto, Mayra Tuboi Lamonica, Gustavo, Urbano, Ricardo Villela Prado, Nivaldo, Alonso, Carlos Ferreira Dos Santos, Cristiano, Tonello, Robinson Esteves Pires, Ricardo Fernandes Rezende, Igor, Reis, Fernando Augusto Lima Marson, Erick Pires Ferreira, Camila Vantini Capasso Palamim, Marcelo, Brandao, Tiago Henrique de Souza, Rebecca, Maunsell, Alfeu Accorsi Neto, Guilherme, Accorsi, Murilo Francisco Fernandes, Camila, Machareth, Barbara Viegas Moura, Vanessa, Dias, Luciano, Guarienti, Lia Regina de Sampaio, Cristiano, Vendrame, Tatiane Amorim Coelho, Karin, Becker, Andre, Dias, Camila Girardi Fachin, Monica Maria Gomes-da-Silva, Isabela, Moraes, Amanda, Pinto, Adriano Seikiti Stychnicki, Nathalia Siqueira Julio, José Mauro Dos Santos, Humberto Fenner Lyra Junior, João Carlos Costa de Oliveira, Tiago Rafael Onzi, Marlus Tavares Gerber, Filipe Osni Coelho, Janaína Carla da Silva, Carolina, Panis, Daniel, Rech, Melissa, Avelino, Lais, Botacin, Mateus Capuzzo Gonçalves, Amanda Lira Dos Santos Leite, Laercio, Pol-Fachin, Tainá Santos Bezerra, Alcimar Lavareda Dos Santos Junior Alcimar, Robson, Amorim, Maria Eduarda Bellotti Leão, João José Corrêa Bergamasco, Cintia Cardoso Pinheiro, Rubem Alves Da Silva Neto, Elaine Francisca De Araújo, Lilian, Guimaraes, Tatiana, Liborio-Kimura, Isabelle Melo da Camara, Victor Ripardo Siqueira, Juan, Rodriguez, Jeancarllo, Silva, Rubem Alves Silva Junior, Cláudio, Cardoso, Andre, Guimaraes, Wislene Sarajane Moreira Alves, Agna Soares Da Silva Menezes, Marcelo, Araujo, Kattiucy, Brito, Josie Marcelle Lira Albuquerque, Jairo Alberto Dussan-Sarria, Andressa, Souza, Andre Ricardo Stüker, Tiago, Bresciani, Luciana Cadore Stefani, Leandro Totti Cavazzola, Tainá, Costa, Matheus, Dasqueve, Gustavo De Bacco Marangon, Otávio Ritter Silveira Martins, Josy, Rodrigues, Guilherme Roloff Cardoso, Brasil Silva Neto, Tilaê, Soares, Aline, Zanella, Lucas Torelly Filippi, Enilde Eloena Guerra, Ricardo Pedrini Cruz, Antonio Nocchi Kalil, Gustavo, Laporte, Moacyr, Salem, Murilo de Lima Brazan, Caio Antonio de Campos Prado, Elaine Christine Dantas Moises, Hilda Satie Suto, Alice Gadotti Yasuda, Ana Carolina Tagliatti Zani, Roberto Cardoso Cardoso Dos Santos, Geraldo, Duarte, Edwaldo Edner Joviliano, Carolina Lourenço Gomes Dos Santos, Silvana Maria Quintana, Edwin, Tamashiro, Fabiana Cardoso Pereira Valera, Marília Veccechi Bijos Zaccaro, Isis, Andreotti, Leonardo, Lima, Wilson Salgado Jr, Alonço da Cunha Viana Júnior, Lana, Moutinho, Cora Pichler de Oliveira, Isabela Trindade Martins, Isabela Vieira Toledo, Marco Antonio Correa Guimaraes-Filho, Rodrigo, Arrivabeno, Claudio Bovolenta Murta, Danniel Frade Said, Jose Pontes Junior, Felipe Guimarães Pugliesi, Paulo, Gregorio, Alessandro, Mariani, Fabio, Minamoto, Juliana Lourenço da Silva, Bruno, Muller, Caio, Zanon, Vladimir, C Carvalho, Ana Lucia Munhoz Lima, Priscila, R Oliveira, Jorge Dos Santos Silva, Mariana Faccini Teixeira, Marco, Kulcsar, Leandro, Matos, Kamilla Schmitz Nunes, Joel Abdala Junior, Emne, Abdallah, Genival Barbosa Carvalho, Igor Correia de Farias, Cassia da Silva, Fabio Fernando Eloi Pinto, Luciana, Facure, André, Godoy, Bruna, Kupper, Fernanda, Leite, Matheus de Melo Lôbo, Henrique, Mantoan, Narimã, Marques, Tomas, Marques, João Paulo Medici, Silvio Melo Torres, Katheryne Merlos Garcia, Rafael Ribeiro Meduna, Ana Carolina Scintini Herbst, Silvana Soares Dos Santos, Bruna Tirapelli Gonçalves, Marcelo, Antonini, Carolina, Brienze, José Francisco Farah, Rodrigo, Gonçalves, Vinicius, Machado, Luis Roberto Nadal, Danilo Nadal Rodrigues, Adrieli, Pansani, Maria Luiza Rocha, Marcelo, Simonsen, Daniela, Tsuchiya, Rafaela, Vasques, Jorge, Amorim, Ana Alyra Carvalho, Rebeca, Correia, Brena Costa Dos Santos, Henrique Jorge Guedes Neto, Luis, Nakano, Mariana, Pereda, Vladimir, Vasconcelos, Jamile Barakat Awada, Guilherme, Gava, Tiago Riuji Ijichi, Nam Jin Kim, Rafael, Nunes, Fabio, Pinto, Thiago Henrique Sigoli Pereira, Gustavo Jardim Volpe, Arthur, Gatti, Caroline, Nardi, Ramon, Oliva, Layze Braz de Oliveira, Herica Emilia Félix de Carvalho, Ivonizete Pires Ribeiro, Gabriel Renan Soares Rodrigues, Álvaro Francisco Lopes de Sousa, Michel, Chebel, Paulo Henrique de Sousa Fernandes, Marcelo Augusto Faria Freitas, Juliano Rodrigues da Cunha, Zeenia, Ather, Dobromir, Dimitrov, Emil, Filipov, Elitsa, Gyokova, Ivelina, Ilieva, Tsvetomir, Ivanov, Martin, Karamanliev, Vasil, Neykov, Boyko, Atanasov, Nikolay, Belev, Paolina, Kamenova, Kaloyan, Tonev, Tsanko, Yotsov, Evguenia, Hristova, Kolyo, Spassov, Tsanko, Tsankov, Dragomir, Dardanov, Petar, Gribnev, Manol, Sokolov, James, Brown, John, Tanyi, Heather, Hurdle, Anthony, Maclean, Michael, Sander, Salim Al Riyami, Krittika, Bali, David, Bigam, Khaled, Dajani, Mehran, Anvari, Rafik, Bolis, David, Choi, Susan, Ellis, Michael, Gupta, Wael, Hanna, Dennis, Hong, Cynthia, Horner, Lea, Luketic, Peter, Moisiuk, Yaron, Shargall, Hilda, Alfaro, Nawar, Alkhamesi, Laura, Allen, Muriel, Brackstone, Eunice, Chan, Davy, Cheng, Jason, Chui, Nelson, Gonzalez, Brent, Lanting, S Danielle MacNeil, Robert, Mayer, Jacob, Mcgee, Mahesh, Nagappa, Nicholas, Power, Agya, Prempeh, Mehdi, Qiabi, Hassan, Razvi, Emil, Schemitsch, Herman, Sehmbi, Ushma, Shah, Yamini, Subramani, Edward, Vasarhelyi, Kelly, Vogt, Homer, Yang, Ali Ghorbani Abdehgah, Saba, Balvardi, Liane, Feldman, Julio Flavio Fiore Jr, Melissa, Hanson, Brent, Hopkins, Pepa, Kaneva, Lawrence, Lee, Julia, Leonard, Jad, Abou-Khalil, Andre, Martel, James, Stevenson, Susan, Lee, Richard, Merchant, Samuel, Avoine, Laurence, Belanger, Mathieu, Belanger, Etienne, Belzile, Anne-Sophie, Blais, Sofia, Boucher-Kovalik, Cindy, Boulanger-Gobeil, Etienne, Cardinal, Pierre-Olivier, Champagne, Jonathan, Cloutier, Simon, Corriveau-Durand, Mathieu, Cote, Maxime, Cote, Mathilde, Côté, Valérie, Courval, Suzanne, Demers, Christine, Desbiens, Mehdi El Ouazzani, Karine, Girard, Ève-Marie, Girard, Karo, Gosselin, Helene, Khuong, Nathalie, Labrecque, Eve-Lyne, Langlais, Audrey, Larouche, Andréane, Lavallée, Madeleine, Lemyre, Sarah, Maheux-Lacroix, Melissa, Marien, Patrick, Marin, Julie, Mauger, Genevieve, Milot, Sylvie, Nadeau, Sebastien, Nguyen, Mélinda, Paris, Stéphane, Pelet, Marie, Plante, Carole, Plante, Frederic, Pouliot, Marie Claude Renaud, Mathilde, Sarlabous, Isabelle, Schmit, Raphaël, St-Germain, Brian, Johnston, Nicole, Labine, Amit, Persad, Hong, Pham, Melissa, Wood, Riordan, Azam, Amit, Atrey, Andrew, Beckett, Daniel, Cohen, Sunit, Das, Julian, Daza, Cheryl, Dunkerton, Yosef, Ellenbogen, Ciara, Hanley, Sorcha, Kellett, Amir, Khoshbin, Karim, Ladha, Amanda, Mcfarlan, Spencer, Montgomery, Janneth, Pazmino-Canizares, Hrishikesh, Suresh, Ravleen, Vasdev, Maira, Ahmed, Fred, Gentili, Aristotelis, Kalyvas, Matthias, Millesi, Can, Sarica, Taariq, Shaikh, Leslie, St, Jacques, Raha, Tabasinejad, Gelareh, Zadeh, Marvin, Hsiao, Nicole, Jedrzejko, Peter, Black, Claire, Broe, Charlotte, Dandurand, Rebecca, Grey, Philemon, Leung, Andrew, Lindberg, Juan Mata Gutierrez, Kelly, Mayson, Adam, Meneghetti, Drew, Phillips, John, Street, Carolina Carvajal Calderón, Daniel Alejandro Donoso Pizarro, Esteban, Fernández, Ángela, Molero, Nastassja, Mutarello, Jorge Núñez Lucic, Katherine Ochoa Gaete, Catalina Ruiz Lopez, Rina, Sepúlveda, Camila, Ulloa, Mauricio, Barreda, Matias, Dallaserra, Matías Günther Wood, Mauricio Sandoval Tobar, Francisco, Garcia-Huidobro, Jimena, Dona, Carolina Soto Diez, Daniel, Igor, Javier, Mena, José Tomás Reyes, Catalina Arredondo Soto, Jose, Campos, Javier, Gonzalez, Barbara, Rivera, Jaime, Altamirano-Villarroel, David, Cohn, Luis Marin de Amesti, Pedro, Recabal, Camilo, Sandoval, Bruno Catoia Fonseca, Monica, Contador, Andres, Hodali, Camila, Pincheira, Andrea Ramos Mantilla, Claudio Salas Garrido, Janina, Torres, Marco, Valenzuela, Zehua, Chen, Jiankun, Hu, Jin, Tao, Kun, Yang, Yuexin, Zhang, Yuan, Chen, Wang, Cunchuan, Wah, Yang, Xueli, Bai, Tingbo, Liang, Tao, Ma, Ning, Pu, Hanlin, Yin, Camilo, Caicedo, Diego Felipe Tellez Beltran, Alejandro, Escobar, Carolina Perez Granados, Lisbeth Alexandra Urueña Pinzon, Carlos, Bonilla, Diana, Santana, Oscar, Serrano, Andrea, Garcia, Fernando Giron Luque, Nasly, G Patino-Jaramillo, Laura Giselle Contreras Baquero, Nestor Augusto Muñoz Botero, Jhoana Andrea Murillo Castellanos, Andrea Juliana Vega Calvera, Lina, M Acosta Buitrago, Maria Paz Bohórquez-Tarazona, Paulo Andrés Cabrera Rivera, J Felipe Casas, Valeria Cormane Alfaro, Julian, Corso, Bayron, Guerra, Albert Franz Guerrero-Becerra, Akram Kadamani Abiyomaa, Felix Ramon Montes, Manuel Santiago Mosquera Paz, Camilo Andrés Polanía Sandoval, Natalia, Quintana, Carlos Fernando Roman Ortega, Carlos, Santacruz, Manuela, Téllez, Camilo Alejandro Velandia Sánchez, Fernando, Arias-Amézquita, Luis Felipe Cabrera Vargas, Natalia Cortes Murgueitio, Elkin, Escorcia, Kemel Ahmed Ghotme Ghotme, Jorge Luis Gomez-Mayorga, Alvaro Felipe Guerrero Vergel, Gabriel, Herrera-Almario, Eduardo, Londono-Schimmer, Juan, A Mejia, Guillermo, Monsalve, Camilo, Rodriguez, Juan Nicolas Rodriguez Niño, Luis Martín Rodríguez Ortegón, Daniel, Sanabria, Andres, Alvarez, Arnulfo, Andrade, Javier, Ardila-Montealegre, David, Baquero, Edgar Mauricio Barrios Vidales, María Alejandra Caicedo Giraldo, María Camila Carvajal, Maria, Castillo, Maria Carolina Castillo Florez, María Angelica Cendales, Danny Conde Monroy, Henry, Cortes, Mario, Daniel, Jairo De la Peña, Elena Leonor Delgado-Nieto, Hernando, Espitia, Carlos Figueroa Avendaño, Edgar Oswaldo Hernandez Burgos, Andres, Isaza-Restrepo, German, Londono, Margarita Maria Maldonado, Andrea, Montenegro, Juan Carlos Navarro, Jorge, Navarro-Alean, Katherine Parra Abaunza, Eliana, Pulido, Erika, M Ramírez Amaya, Carlos Eduardo Rey Chaves, Natalia Andrea Rivera Rincón, William Mauricio Riveros Castillo, Lizeth Rodriguez Sanchez, Wilson, Rubiano, Maria, Russi, Juan Carlos Sabogal Olarte, Javier Mauricio Salgado Tovar, Maria Juliana Sanchez, David Mauricio Solano Varela, Paula Torres Gomez, Marcial, Trillos, Ana María Vargas Patiño, Felipe, Vargas-Barato, Juan Pablo Villate Leon, María Alejandra Wagner Useche, Jesus, Acosta, Adriana, Almeciga, Luis Becerra Mendez, Rafael Jose Beltran, Ana, Bonilla, Miguel, Buitrago, Marino, Cabrera, Pedro Hernando Calderon Quiroz, Diego, Camacho-Nieto, Carlos Andrés Carvajal Fierro, Sergio Cervera Bonilla, Sandra, Diaz, Helena, Facundo, Jorge, Forero, Mauricio Garcia Mora, Karena Victoria Garcia Tirado, German Fabian Godoy Perez, Felipe, Gonzalez, Oscar, Guevara, Jairo Alonso Hernandez, David Ricardo Herrera Mora, Juan David Lalinde, Carlos, Lehmann, Eduardo Leon Llanos, Byron Eduardo Lopez De Mesa Lopez, Ivan, Mariño, Monica, Medina, Raúl Eduardo Pinilla Morales, Angela, Puerto, Andrea, Quintero-Ortíz, Juliana Rendón Hernández, Elio Fabio Sánchez Cortés, Alvaro Eduardo Sánchez Hernández, Raul, Suarez, Oscar, Suescun, Marco, Vanegas, Rodolfo, Varela, Jorge Luis Velez Bernal, David, Viveros-Carreño, Daniela Camargo Gómez, Angelica, Fletcher, Abel, Merchan, Euler Javier Burbano Luna, Indira, Cujiño, Mauricio Velasquez Galvis, Lina Maria Vergara Galliadi, Orlando Abonia Gonzalez Abonia Gonzalez, Maria Fernanda Acuna Saravia, Roberto, Arroyave, Jose Maria Barreto Angulo, Francisco Javier Bonilla-Escobar, Uriel, Cardona, Ivan Castañeda Giacometto, José Luis Castillo, Diego Fernando Castillo-Cobaleda, Diego Jose Caycedo Garcia, Brenda Marcela Coll Tello, Juan Carlos Dueñas-Ramirez, Oscar Andres Escobar Vidarte, Luis, Figueroa, Herney, Garcia-Perdomo, Alden, Gomez, Laura, Gomez, Alejandro, Gomez, Ana María Grande-Gil, David, Guarin, Natalia, Guzman, Enrique Herrera Castañeda, Marisol, Hinaoui, Anuar Armando Idrobo Escobar, Christian Kammerer Kammerer, Sergio, Leon, Carlos Antonio Llanos Lucero, Angie, López, Alexander Maximiliano Martinez-Blanco, Antonio José Montoya Casella, Ricardo Andres Niño Corredor, Sebastian, Ordoñez, Diego Alfredo Palta Uribe, 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Baelum, Mark Bremholm Ellebaek, Signe Bremholm Ellebaek, Anders, Hogh, Maria, Acosta, Yancy, Acosta, Pedro, Baez, Luis Alfredo Betances, Luis Rodolfo Bonilla, Daniel, Cabreja, Wilton Cabrera Cruz, María Mabel Collado Expósito, Aldo, Crespo, Octavio, Cruz-Pineda, Claudio Samuel D'óleo García, Pedro, Díaz, Remberto, Escoto, Jatnna, Figueroa, Luis, Garcia, U Garcia-Dubus Rodriguez, Humberto, Gomez, Adrian, Grullon, Fatherin, Guerrero, Lillian, Guzman, Thelma Rocío Jiménez Mosquea, Engels, Lazala, Ariela, Lopez, Leeany Maletta Francisco, Jhomayri, Mercado, Herisardy, Munoz, Jeffrey, Paulino, Maricely Ambar Perez Fernandez, Rudeily, Reyes, Lilia Rosa Reyes Guilamo, Ruben, Rivas, Claudia Alejandra Rivas Torres, Ada, Rodríguez, Madelin Tamar Rosario Villa, Eleazar, Santana, Joel, Soto, Nassin, Tactuk, Cristina Kristel Tonos Sardiñas, Raul, Ubinas, Jose, Victoria, Aaron, Villegas, Ricardo, Acra-Tolari, Larissa, Beltran, Luis Fernand Betances, Alejandro, Blaubach, Denisse Idalia Campos Mejía, Nathalia, Capellan, María Fernanda Cedeño Bruzual, Saray Cordero Spencer, Gabriella Cuevas Lantigua, Luis De Jesus, Gabriela, Díaz, Pedro Pablo Díaz Vásquez, Karla, Disla, Jesús Antonio Echavarría Uceta, Paola Irina Eusebio Jimenez, Damaris, Fernandez, Marlin Fernandez Camilo, Jiomar Manuel Figueroa Germosen, Maruel, Fortunato, Leyla Gabriel Fernández, Alicia German Dihmes, Héctor, Herrera, Elizabeth Leon Cuevas, Jose Alejandro Mata, Mirian Mateo De La Cruz, Dolores Mejia De la Cruz, Marcos, Mirambeaux, Fabio Ortiz De La Cruz, Henry, Paulino, Gabriela, Pelletier, Merycarla, Pichardo, Rodriguez Pumarol Próspero Enrique, Julio, Rivas, Ann Stephany Sanchez Marmolejos, Roman Santana Santana, Irina Suero Almanzar, María Magdalena Vásquez Sánchez, Nicolás, Campuzano, José Ricardo Negrete Ocampo, Maria, Armas, Alvaro Santiago LeMarie Guerra, Gustavo León Vizcaya, Omar Ahmed Abdelwahab, Ahmed, O Elmehrath, Mohammed Ezzat Mostafa, Gamal, Amira, Ibrahim, Sallam, Mohamed, Sherief, Ahmed, Abdelmajeed, Mostafa, Abdou, Ahmed Abo Shanab, Aya, Abodeeb, Roger, Aboelkhel, Nour Eldin Abosamak, Amna Abou Bakr, Samar, Aboubakr, Yossof, Abouelnagah, Omar, Aboumadawy, Dina, Adel, Nermeen, Afifi, Sara, Ahmed, Abedelrahman, Ahmed, Mohamed Al Sayed, Abdelrahman, Alberkamy, Mohamed, Aldahma, Ahmed, Ali, Mostafa, Ali, Mohamed Amin Bakr, Alaa, Anter, Doaa, Asal, Fouad, Ashoush, Olfat, Ashraf, Abdel Rahman Ashraf, Rewan, Atta, Salma, Badr, Mohamed, Bahaaeldin, Mostafa, Bastawesy, Sara, Darwish, Rasha El Kharashy, Ziad, Elassar, Seifeldin, Elbadawy, Dina, Elkhity, Alromisaa, Elsaka, Manal, Elsayed, Mostafa Elsayed Elsayed Hewalla, Mohamed, Elshafey, Youssof, Eshac, Fares, Eshac, Amr, Essameldin, Moataz, Ewedah, Yara, Ezz, Mohamed, Farag, Inas, Gadelkarim, Ziyad, Gadelrab, Dina, Gamal, Mira, Ghaly, Nathalie, Girgis, Omar, Gouda, Nancy, H El Goweini, Nour, Hafez, Youssef, Hafez, Abdelkader Hamed Abdin, Rodina, Hanno, Aliaa, Hassanin, Mohamed, Hassanin, Hanan, M Hemead, Abdelrahman, Hemida, Maher, Hosain, Ahmed, Hossam, Hamza Hussein Aly Salama Aly, Mohamed, Ibrahim, Abdelrahman, Ibrahim, Nourhan, Ibrahim, Noha Mohamed Salah Ibrahim Moussa Hamouda, Monica, Iskander, Islam, Khalifa, Mostafa, Kotb, Nada, Mahmoud, Alaa Mahmoud Abo Shabana, Nora, Mamdouh, Maram, Metwalli, Khaled, Metwally, Mahmoud, Moghazy, Moustafa, Mohamed, Mohamed, Mourad, Esraa, Moustafa, Kamilia, Mubarek, Nour Eldin Nader, Ahmed, Nasser, Samaa, Omar, Mostafa Shehata Qatora, Mohamed, Ragab, Marawan, Ragal, Dina, Ramadan, Rana, Ramadan, Sara, Ramadan, John, Romany, Ahmed, Sabry, Yasmeen, Said, Sara, Salamah, Ahmed Mostafa Saleh, Mona Saleh Mesbah Mohamed Elkaffas, Alaa, Salem, Hashem, Salim, Ahmed, Samih, Ahmed Samir Abdelaal, Ahmed, Shaheen, Yassmeen Sharafeldin Mohammed, Abdelrahman, Shehata, Mohamed, Shemeis, Karim, Shenit, Mennatallah, Sheta, Asmaa, Soffar, Yousef, Tanas, Ahmed, Tarek, Nermin, Yehia, Omar Khaled Mohamed Eid, Ammar Yasser Abdulfattah, Ahmed, Elsaghir, Mohamed Fouad Elganainy, Omar Ibrahim Elsayed, Omar, Elmandouh, Omar, Hamam, Mostafa Ahmed Shehata, Areej, A Abdelaziz, Ahmed, M Abbas, Wael Abd El-Ghani, Hossam Aldein, S Abd Elazeem, Mustafa Abd Elsayed, Ahmed Yassien Abd-Elkariem, Shimaa, Abdalla, Mahmoud, Abdel-Aleem, Khaled, Abdelazeem, Mahmoud, Abdelfattah, Mohammed, Abdelhafez, Mohamed, M Abdelkarem, Ali, Abdelraouf, Lamess, Abdullaha, Hossam, Abubeih, Moaiad Eldin Ahmed, Nagm Eldin Abu Elnga Ahmed, Ahmed, Ahmed, Sarah Ahmed Saad, Sherif, Alaa, Ali, Alhussaini, Abdelrahman Ahmed Abdelrahman Ali, Ibrahim, Ali, Wagdi, Ali, Mohamed Ali Mohamed, Mohamed, Ashraf, Muhammad, Bassiouni, Mohamed, G El-Adawy, Mohammad, El-Sharkawi, Hussein, Elkhayat, Khaled, Elmaghraby, Shady, Elsdfy, Mohamed, Elsharkawy, Almoutaz, Eltayeb, Mohamed Esmat Mohamed, Esraa, Essam, Mahmoud, Fahd, Osama, Farouk, Rabea, Gadelkareem, Ahmed, Ghoneim, Mohammed Hamada Takrouney, Ahmed, Hamdan, Abd El-Rahman Hamed, Ahmad, Hasan, Mohamed Abdelghafor Hassanin, Islam, Hawal, Kerollos, Henes, Mohamed Omar Herdan, Helal, F Hetta, Omar, Ibrahem, Mostafa, Ibrahim, Islam, H Ibrahim, Mahmoud, Kamel, Mohamed, Khallaf, Shrouk, M Elghazaly, Abobakr, Mahfouz, Osman, Mahmoud, Wesam, Mahran, Doha, Mahrous, Abadeer, Marsis, Ayman, Mohamed, Aliae Mohamed Hussein, Amr Mohamed Sayed, Mahmoud, M Mohammed, Ahmed, Mokhtar, Fatma, A Monib, Ahmed, Nageeb, Mariam Albatoul Nageh, Mohammed, Nageh, Nehal Gamal Omar, Abdelrahman, Ragab, Abdelrahman, Ramadan, Abdallah Rashad Temerik, Aya, Sabry, Hadeer, Safwat, Omar, Salah, Ahmed Elhussiny Salah Mahmoud, Ahmed, Saleh, Mahmoud, Sallam, Ahmed, Samir, Reem, Sayad, Esraa, Sayed, Ahmed, S Sedik, Mohammed, Shahine, Antonios, Soliman, Wael, Soliman, Mohamed Gamal Taher, Randa, Wanees, Ebrahim Ahmed Yousof, Ahmed, Youssef, Omar Zein Elabedeen, Ahmed Emad Sayed Hassan, Shrouk Abdel Fattah, Ahmed, Abostate, Samar, Ali, Saad Ali Saad Salama, Mohamed, Allam, Ahmed, Alsadek, Ebrahim, Arafa, Ahmed, Barakat, Mohammed El Sherpiny, Gehad, Elbehairy, Mahmoud, Eleisawy, 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Krause, Frank, Meyer, Salmai, Turial, Bilal, Al-Nawas, Marco Johannes Battista, Jan, Goedeke, Annette, Hasenburg, Julia, Heider, Lena Katharina Mueller, Simon, Zeller, Sina Louisa Patrizia Jentschura, Karl-Friedrich, Kowalewski, Maximilian, Kriegmair, David, Männle, Christoph, Reissfelder, Nicole, Rotter, Claudia, Scherl, Steffen, Seyfried, Andreas, Kirschniak, Jens, Rolinger, Peter, Wilhelm, Franz, G Bader, Stephanie, Ottl, Alexandra Viktoria Behr, Alexandros, Diamantis, Andreas, Fichter, Florian, Grill, Matthias, Heck, Daniel, Jira, Michael, Kallmayer, Florestan, Koll, Stefan, Luhne, Bernhard, Meyer, Robert, Patachia, Ilaria, Pergolini, Seyer, Safi, Christoph, Schäffer, Moritz, Schirren, Helmut, Wegmann, Markus, Wirth, Zhaojun, Zhu, Ughur, Aghamaliyev, Mahmoud, Almaghrabi, Wolfgang, Böcker, Jan, Bruder, Konstantin, Frank, Viktoria, Herterich, Verena, Huber, Matthias, Ilmer, Christian, Kammerlander, Carl, Neuerburg, Viktor, H von Ehrlich-Treuenstätt, Jens, Werner, Nikolaus, Börner, 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Enrico, Gelarda, Giorgio, Giraudo, Maria Carmela Giuffrida, Alessandra, Marano, Elena, Olearo, Vincenzo Pruiti Ciarello, Andrea, Puppo, Valentina, Testa, Marco, Giacometti, Sandro, Zonta, Eleonora, Monti, Andrea, Porta, Daniele, Sambucci, Arianna, Birindelli, Barbara, Carrara, Bruno, Compagnoni, Roberto Del Giudice, Sara Elisabetta Dester, Daniele, Lomiento, Silvia, Ruggiero, Lucio, Taglietti, Fabio, Viotti, Domenico, Lacavalla, Savino, Occhionorelli, Michele, Rubbini, Massimiliano, Bernabei, Nicolò, Fabbri, Marta, Fazzin, Carlo, V Feo, Marco, Torchiaro, Renato, Costi, Edoardo, Virgilio, Lorenzo, Arlia, Giuseppe, Barbato, Ilenia, Bartolini, Andrea, Bottari, Chiara, Bruno, Alessandro, Bruscino, Carlotta, Checcucci, Fabio, Cianchi, Francesco, Coratti, Rosita De Vincenti, Annamaria Di Bella, Massimiliano, Fambrini, Laura, Fortuna, Oreste, Gallo, Giacomo, Gigliucci, Luca Giovanni Locatello, Gherardo, Maltinti, Jacopo, Martellucci, Paolo, Prosperi, Maria Novella Ringressi, Flavia, Sorbi, 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Massimiliano, Gennaro, Lorenzo, Giannini, Marcello, Guaglio, Marco, Guzzo, Andrea, Leva, Alberto, Macchi, Elena, Manzo, Fabio, Martinelli, Ilaria, Mattavelli, Vincenzo Maria Mazzaferro, Francesco, Raspagliesi, Luigi, Rolli, Laura, Sala, Roberto, Salvioni, Mario, Santinami, Silvia, Segattini, Luca, Sorrentino, Carlotta, Zaborra, Alexandre, Anesi, Gianmaria Casoni Pattacini, Mattia Di Bartolomeo, Francesca, Pecchini, Arrigo, Pellacani, Micaela, Piccoli, Federico, Fusini, Andrea, Gattolin, Marco, Migliore, Roberto, Rimonda, Diego, Sasia, Elisabetta, Travaglio, Federica, Brunetti, Marco, Cereda, Marco, Ceresoli, Luca, Cigagna, Cristina, Dell'Oro, Alessandro, Fogliati, Robert, Fruscio, Tommaso, Grassi, Maini Marzia Isabella, Luca Carlo Nespoli, Massimo, Oldani, Sara, Ornaghi, Nicolò, Tamini, Carmine, Antropoli, Antonio, Castaldi, Alessio, Palumbo, Gaia, Altieri, Umberto, Bracale, Francesco, Corcione, Marcello De Luca, Giovanni Domenico De Palma, Maria Michela Di Nuzzo, Ruggero, Lionetti, 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Matteo, Filardo, Marika Sharmayne Milani, Franco, Ragni, Andrea de Manzoni Garberini, Edoardo, Baldini, Diana, Carpaneto, Michele, Cauteruccio, Corrado, Ciatti, Luigi, Conti, Serena, Gattoni, Pietro, Maniscalco, Gerardo, Palmieri, Calogero Puma Pagliarello, Giuseppe, Caristo, Raffaele, Galleano, Michele, Malerba, Marcello, Calabrò, Francesca, Farnesi, Elia Giuseppe Lunghi, Andrea, Muratore, Nicoletta Sveva Pipitone Federico, Joel Reuben Abel, Lorenzo, Andreani, Darienzo, Antonio, Vittorio, Aprile, Riccardo, Balestri, Giacomo, Benettini, Stefano, Berrettini, Luca, Bruschini, Massimo, Chiarugi, Federico, Coccolini, Simone, Colangeli, Camilla, Cremonini, Lodovica Cristofani Mencacci, Iacopo, Dallan, Silvia De Santi, Gregorio Di Franco, Lorena Di Girolami, Giacomo, Fiacchini, Niccolò, Furbetta, Stylianos, Korasidis, Marco, Lucchi, Andrea, Morandi, Luca, Morelli, Serena, Musetti, Carlo Maria Neri, Matteo, Palmeri, Miriana, Picariello, Francesco, Porcelli, Marco, Puccini, Nicolo, Roffi, 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Bianchi, Giuseppe, Bianco, Alberto, Biondi, Paola, Campennì, Valerio, Cozza, Sabatino, D'Archi, Domenico, D'Ugo, Veronica De Simone, Marta Di Grezia, Sofia Di Lorenzo, Federica, Ferracci, Valeria, Fico, Gianluca, Franceschini, Pietro, Fransvea, Giulio, Gasparini, Luca, Gordini, Antonio La Greca, Francesco, Litta, Celestino Pio Lombardi, Angelo Alessandro Marra, Angelo, Parello, Marco Maria Pascale, Romeo, Patini, Gilda, Pepe, Roberto, Persiani, Caterina, Puccioni, Carlo, Ratto, Fausto, Rosa, Gianmarco, Saponaro, Lorenzo, Scardina, Tedesco, Silvia, Giuseppe, Tropeano, Maria, Benevolo, Daniele, Bugada, Flaminia, Campo, Maria Gabriella Dona, Valentina, Manciocco, Paolo, Marchesi, Riccardo, Mastroianni, Francesco, Mazzola, Silvia, Moretto, Raul, Pellini, Gerardo, Petruzzi, Barbara, Pichi, Giuseppe, Simone, Gabriele, Tuderti, Jacopo, Zocchi, Luigi Marino Cosentino, Andrea, Sagnotta, Roberta, Angelico, Vittoria, Bellato, Michela, Campanelli, Marzia, Franceschilli, Michele, Grande, Giorgio, Lisi, Tommaso Maria Manzia, Lorenzo, Petagna, Bruno, Sensi, Giuseppe, Sica, Leandro, Siragusa, Giuseppe, Tisone, Marco, Assenza, Barbara, Binda, Massimo, Biondi, Gioia, Brachini, Placido, Bruzzaniti, Mauro, Casagrande, Flavia, Ciccarone, Pierfranco Maria Cicerchia, Bruno, Cirillo, Daniele, Crocetti, Giancarlo, D'Ambrosio, Vito, D'Andrea, Francesca De Felice, Giorgio De Toma, Carlo Della Rocca, Giulia, Duranti, Pietro, Familiari, Enrico, Fiori, Giovanni Battista Fonsi, Alessandro, Frati, Stefania La Rocca, Filippo La Torre, Pierfrancesco, Lapolla, Giovanni, Marruzzo, Simona, Meneghini, Andrea, Mingoli, Andrea, Picchetto, Antonella, Polimeni, Diego, Ribuffo, Maurizio, Salvati, Antonio, Santoro, Paolo, Sapienza, Luigi, Simonelli, Valentino, Valentini, Martina, Zambon, Giuseppa, Zancana, Emma, Zuppi, Simone, D'Annunzio, Cosimo De Nunzio, Silvia, Fiorelli, Mohsen, Ibrahim, Chiara, Loffredo, Domenico, Massullo, Cecilia, Menna, Rocco, Monica, Massimiliano, Pelli, Erino Angelo Rendina, Leonardo, Teodonio, Andrea, Tubaro, Giulio, Argenio, Giulio, Accarino, Accarino, Giancarlo, Antonio Nicola Giordano, Luca, Cardinali, Elisa, Sebastiani, Grazia, Travaglini, Erika, Andreatta, Emanuele Luigi Giuseppe Asti, Daniele, Bernardi, Luigi, Bonavina, Caterina, Froiio, Andrea, Lovece, Chiara, Copelli, Alfonso, Manfuso, Pasquale Di Maio, Marco, Giudice, Oreste, Iocca, Rosario, Cennamo, Tommaso, Cornali, Francesco Di Marzo, Cristian, Altana, Francesco, Bussu, Giampiero, Capobianco, Anna Giacomina Carta, Sandro, Ciccarello, Maria Laura Cossu, Pietrina, Cottu, Giacomo De Riu, Salvatore, Dessole, Francesco, Dessole, Salvatora, Dettori, Carlo, Doria, Alessandro, Fancellu, Claudio, F Feo, Giorgio Carlo Ginesu, Giuliana, Giuliani, Marco Giuseppe Iannuccelli, Massimo, Madonia, Roberto, Mancino, Olindo, Massarelli, Gianfranco, Meloni, Fabio, Milia, Andrea, Mulliri, Teresa, Perra, Marco, Petrillo, Antonio, Piras, Franco, Piredda, Francesco, Pisanu, Alberto, Porcu, Davide, Rizzo, Angelino, Sanna, Antonio Mario Scanu, Fabrizio, Scognamillo, Damiano, Soma, Anna Rita Tanca, Alessandro, Tedde, Matteo, Tedde, Luigi Angelo Vaira, Andrea Bartalini Cinughi de Pazzi, Osvaldo Carpineto Samorani, Daniele, Fusario, Luigi, Marano, Gaia, Oldrà, Anna Lisa Pesce, Stefania Angela Piccioni, Luca, Resca, Vincenzo, Ricchiuti, Franco, Roviello, Vinno, Savelli, Alberto, Abrate, Pierpaolo, Bordoni, Lorenzo, Bosio, Guglielmo, Clarizia, Francesco, Fleres, Marco, Franzini, Antonio, Fratto, Pierluigi, Giumelli, Alessandro, Grechi, Alessandro, Longhini, Fabrizio, Lorusso, Elisa, Scarnecchia, Federica, Scolari, Alessandro, Spolini, Vincenzo, Maiuri, Matteo, Papandrea, Arturo, Roncone, Lorenzo, Conti, Andrea, Rizzi, Marco, Rovagnati, Alberto, Brolese, Tommaso, Cai, Francesco Antonio Ciarleglio, Francesca, Dalprà, Gianni, Malossini, Liliana, Mereu, Irene, Tamanini, Saverio, Tateo, Giovanni, Viel, Enrico, Battistella, Paolo Boscolo Rizzo, Cristoforo, Fabbris, Marco, Massani, Giacomo, Spinato, Roberta, Tutino, Ugo, Grossi, Alessandro, Iacomino, Simone, Novello, Maurizio, Romano, Serena, Rossi, Giulio, Santoro, Giacomo, Zanus, Sokol, Trungu, Giada, Aizza, Gabriele, Bellio, Selene, Bogoni, Marina, Bortul, Biagio, Casagranda, Sara, Cortinovis, Nicolò de Manzini, Davide, Drigo, Paola, Germani, Manuela, Mastronardi, Lucia, Paiano, Silvia, Palmisano, Pier Luigi Filosso, Francesco, Guerrera, Matteo, Marro, Mauro, Rinaldi, Enrico, Ruffini, Stefano, Salizzoni, Laura, Bardelli, Mattia, Berselli, Giacomo, Borroni, Eugenio, Cocozza, Matteo, Desio, Bottazzoli, Elisa, Giuseppe, Ietto, Valentina, Iori, Domenico, Iovino, Lorenzo, Livraghi, Valentina, Marchionini, Stefano, Megna, Emma Amal Nahal, Mara, Palumbo, Valeria, Quintodei, Alessandra, Zullo, Lucrezia, D'Alimonte, Giovanni, Pirozzolo, Chiara, Vignotto, Tommaso, Campagnaro, Andrea, Caravati, Simone, Conci, Carlotta De Cristofaro, Gabriele, Gecchele, Tommaso, Giuliani, Jacopo, Graziosi, Alfredo, Guglielmi, Salvatore, Paiella, Corrado, 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Mubaydeen, Husam, Sarayrah, Mohammad Abdel Elah, A Tarawneh, Mohammad Yousef Karasneh, Amany, Zurgan, Mohammad, Alassaf, Sayel, H Alzraikat, Justin, Z Amarin, Ahmed, Hijjawi, Haya, H Suradi, Louay, Y Zaghlol, Ahmad, Abdalah, Ghaida, Abdallah, Ammar Abu Tarieh, Tareq, Abu-Libdeh, Faisal, Abualteen, Murad Al Abdallah, Zakaria Al Bdour, Seif Al Dahabrh, Farah, Al-Kasaji, Zaid Al-Sheikh Ali, Mohammad, Al-Thaher, Tareq, Alnajjar, Mohannad, Alqedrh, Mohammad, Alsaleh, Mohammad, Alzaatreh, Ghandi, Amayreh, Yazeed, Ayasra, Ahmad, Eid, Ibrahim, Ghayada, Khaled Moh'd Ahmed Hasanein, Anas, Hassouneh, Raid, Hijazeen, Majedah, Hmeidan, Ahmed, Khaled, Barihan, Khasawneh, Omar, Kifayeh, Yasser, Lafi, Jasem, Seba, Qusai, Semrin, Fda, Sma, Mohammad, Theab, Haitham, Tumeh, Muna Aba Zaid, Alaa, Abazeed, Bader, Abbad, Osaid, Abbadi, Nizar, Abu-Ishkerih, Malk, Al-Osta, Reham, Al-Zyadat, Bashar Omar Falah Alawneh, Majd, Alhattab, Mohd Mujahed Alkurdieh, Ziad, Awwad, Mohammad, Hammouri, Hamzeh, Hussein, 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Mohammedali, Claude, Mwaria, Ralph, Obure, Sayed Shah Nur Hussein Shah, Chetan, Hirani, Muthoni, Kibunyi, Claire, Mailu, Victor, Mwangi, Roy, Ogenya, Lydia, Osea, Davies, Cheruiyot, Omar, Hirsi, Carolyne, Muiru, Samuel, Wanjara, Chang Woo Kim, Suk Hwan Lee, Ahmad, Almulla, Mustafa, Dashti, Omar, Elghany, Abdullah, Sultan, Husain, Al-Mahmeed, Jasim, Alabbad, Ibtisam, Albader, Shuaib, Aldalal, Mahdi, Baba, Fareed, Abdulsalam, Naser, Alhajri, Athari, Alwael, Brook, Ayele, Hatem, Marie, Ahmed, Zaitoun, Ahmad, M AlAli, Ahmed, Alkhamis, Ous, Alozairi, Sulaiman, Almazeedi, Salman, Alsabah, Mostafa, Abdelkarim, Asmaa Al Rashed, Saud Al Subaie, Tariq, Al-Shaiji, Abdullatif, Al-Terki, Omar, Alhunaidi, Ali, Aljewaied, Khaled, Alzamel, Ahmed, Farag, Hussein, Hayati, Salah, Termos, Sarah, Wood, Maha, Al-Gilani, Mutlaq, Al-Sihan, Haifa, Alotaibi, Dmitrijs, Lobovs, Andrejs, Pcolkins, Armands, Sivins, Ingus Arnolds Apse, Annija Evelīna Berga, Anna, Ivanova, Jevgenijs, Demicevs, Igors, Ivanovs, 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Alameen, Rehab, Alarabi, Alarabi, Alarabi, Aisha, Alelwany, Abdulkarim, Alesmail, Noran, Algadi, Khuloud, Almaqrahi, Hadel, Alosta, Mohamed, Alsharedi, Rasha, Bashir, Mahmoud Ben Ghrema, Sari Bin Nour, Sofian, Elbarouni, Ahmed, Elhadi, Abdulmohimen, A Elkhadar, Esraa, Elkouba, Nabiha, Elmsherghi, Abdulmohimen, Gammoudi, Abdulraouf, Ghariba, Fatima Zayed Gjam, Arwa, Haidar, Hala, Helal, Mohammed, Huwaysh, Ahmed Khalid Alhadheeri, Eslam, Kriem, Halim, Osman, Mohamed Ali Ossman, Marwah, Shilfeet, Laila, Turshani, Nouran, Albishty, Abdulmueti, Alhadi, Salem, Ali, Manal Ahmed Altoumi, Sumayyah Ghayth Bahroun, Eman, Younes, Hana, Atarabulsi, Mohamed, Elshaibi, Abdullmujeeb, Othman, Hayat Ben Hasan, Najat Shaban Ben Hasan, Rabab Shaban Ben Hasan, Vidmantas, Barauskas, Edvinas, Dainius, Zilvinas, Dambrauskas, Albertas, Dauksa, Inga, Dekeryte, Rita, Gudaityte, Kristijonas, Jasaitis, Akvilė, Koženiauskaitė, Virgilijus, Krasauskas, Ausra, Lukosiute-Urboniene, Almantas, Maleckas, Romualdas, Riauka, Vygintas, Šlenfuktas, Saulius, Svagzdys, Kestutis, Urbonas, Tomas, Vanagas, Linas, Venclauskas, Donatas, Venskutonis, Justas, Zilinskas, Marijus, Ambrazevicius, Vilius, Syminas, Oleg, Aliosin, Agne, Cizauskaite, Vitalijus, Eismontas, Jonas, Jurgaitis, Vytenis, Mikutaitis, Donatas, Petrauskas, Narimantas Evaldas Samalavicius, Dainius, Simcikas, Algirdas, Slepavicius, Albinas, Tamosiunas, Vaidotas, Turskis, Bernardas, Vasiliauskas, Laura, Aniukstyte, Audrius, Dulskas, Gediminas, Januška, Justas, Kuliavas, Margarita, Montrimaite, Albertas, Cekauskas, Azuolas Algimantas Kaminskas, Sarunas, Kozenevskis, Tomas, Poskus, Kestutis, Strupas, Arunas, Zelvys, Georges, Decker, Audrey, Noël, Maheriandrianina Fanambinana Voahary Rajaonarivony, Randimbinirina Zakarimanana Lucas, Herimampionona, E Andriantsoa, Mamisoa, B Rasamoelina, Rakotonarivo Aina Andrianina Vatosoa, Liantsoa, Andriamanana, Casimir Fp Rahantasoa Finaritra, Aristide Romain Raherison, Tsirimalala, Rajaobelison, Haritiana, Rakotoarisoa, Maharo, Ramifehiarivo, Solonirina Harinarindra Ranaivoson, Hajamihamina Marina Parfaite Randriantsoa, Narindra Njarasoa Mihaja Razafimanjato, Jeannie Ba Razafindrahita, Solofoarimanana, Solofoarimanana, Guillaume Odilon Tsiambanizafy, Rakotonaivo Mamisoa Judicaël, Corinne Eulalie Solo, Tojomamy Herinjaka Ralaizafindraibe, Fanonjomahasoa Safiry Andofenohasina, Hanta, Rasataharifetra, Vanona Barijaona Razafindraibe, Angelin Sablon Herinirina, Andre, Das, Thanga, Ganapathy, Yohesuwary, Gunarasa, Kalyani, Mariapan, Maathichsudhaar, Muniandy, Mohd Firdauss Osman, Mohd Azem Fathi Mohammad Azmi, Jien Yen Soh, Wan Zainira Wan Zain, Andee Dzulkarnaen Zakaria, Zaidi, Zakaria, Kheng Hooi Chan, Firdaus, Hayati, Syamim, Johan, Jin Jiun Mah, Ratha Krishnan Sriram, Sentilnathan, Subramaniam, Nur Shahirah Binti Muhammad Shahimi, Khairul Hazim Hamdan, Mohd Razali Ibrahim, Guhan, Muthkumaran, Ju Ann Tan, Mohana Raj Thanapal, Dayang Anita Abdul Aziz, Mae-Lynn, Bastion, Mohd Hairul Nizam Harun, Farrah-Hani, Imran, Norshamsiah Md Din, Ayesha Mohd Zain, Mushawiahti, Mustapha, Syed, Nabil, Ainal Adlin Naffi, Abd Jabar Nazimi, Roszalina, Ramli, Bee Hong Soon, Pavin, Bal, Joo Qing Cheng, Mohd Rusdi Draman, Ahmad Nazran Fadzli, Sakina, Ghauth, Weipin, Hung, Suniza, Jamaris, Peng Soon Koh, Sivakumar, Krishnasamy, Yeong Sing Lee, Yew Toong Liew, Jeffery Zk Lim, Raymond Chung Siang Lim, Hiong Chin Lim, Siti Farhan Moh Pauzi, Shireen Anne Nah, Ashvin Krishna Nair, Doris Sin Wen Ng, Yuki Julius Ng We Yong, Kamarajan, Ramayah, Rahmah, Saaid, Anand, Sanmugam, Mee Hoong See, Kanesh Kumaran Seevalingam, Neha, Sethi, Srihari, Singaravel, Syeda Nureena Syed Jafer Hussain Zaidi, Chu Yik Tang, Li Ying Teoh, Kian Boon Wong, Ruben, Xavier, Ahmad Shuib Yahaya, Norhafiza, Ab, Rahman, Islah Munjih Ab, Rashid, Mohd Fahmi Abd Aziz, Mohd Norhisham Azmi Abdul Rahman, Nasser Muhammad Amjad, Shahidah Che Alhadi, Faisal, Elagili, Mohd Nazli Kamarulzaman, Azmi Md Nor, Ahmad Faidzal Othman, Mohd Yusof Sainal, Mat Salleh Sarif, Richelle, Chua, Aini Fahriza Ibrahim, Abdul Rauf Bin Ahmad, Yii Ling Lau, Ka Yee Liew, Kandasami, Palayan, Hui Yu Wong, Jasiah, Zakaria, Nor Azimah Abd Aziz, Norazila Abdul Rahim, Noorneza Abdul Rahman, Bahiyah, Abdullah, Mohamed Faizal Bin Sikkandar, Fatin, Firman, Nik Mohd Hazleigh, Intan Kartika Kamarudin, Shahril, Khalid, Mohd Fairudz Mohd Miswan, Akmal Zulayla Mohd Zahid, Norasyikin, Mustafa, Kadhim, Obaid, Mohd Yusoff Bin Yahaya Yahaya, Ahmad Ramzi Yusoff, Predrag, Andrejevic, Jeremy Borg Myatt, Svetlana, Brincat, Clifford, Caruana, Kurt Lee Chircop, Francesca, Chircop, Daniel Mario Chircop, Charles, Cini, Viktoria, Czok, Melanie, Farrugia, Gabriella, Grima, Fatimah Mj Hassan Almukhariq, Esther, Muscat, Darryl, Pisani, Mohsin Hassan Khan Roshan, Nicholas, Schembri, Mohamed, Shoukry, Neville, Spiteri, Gilbert, Tanti, Ziad Aboharp Hasan, Alberto Bazan Soto, Cedillo Rodrìguez Jonathan Rubén, Gustavo Esteban Lugo Zamudio, David Gerardo Miranda Gómez, José Alfredo Pérez Meave, Victor Pinto Angulo, Antonio Rojas Aguilar, Erik Efrain Sosa Duran, Alejandro Vàzquez Perez, Diego, Arroyo, Jose, Corona-Cruz, Hector, Martinez-Said, Heriberto, Medina-Franco, Manuel, Mendez, Teresa Moreno, Y Suárez Ma, Dolores Orta Díaz, Martha Patricia Pérez de León Vázquez, Angélica Azucena Soto Carvajal, Fidel Soto Hernández, Juan Ignacio Stenner, Adriana Valenzuela López, Mauricio Rene Hernandez, Rey Jesus Romero, Aldo Bernal Hernandez, Ana Olivia Cortes-Flores, Carlos Jose Zuloaga Fernandez Del Valle, Carlos Andres Colunga Tinajero, Jaime, Orozco-Perez, Laura Gabriela Peña Balboa, Guillermo, Yanowsky-Reyes, Víctor Hugo Alcalá Torres, Francisco José Barbosa Camacho, Irma Valeria Brancaccio Perez, Miguel Angel Calderon-Llamas, Aldo Camacho Gomez, Edgar-Joaquin, Cortes-Torres, Esteban, Cueva-Martinez, Oscar Durán Anguiano, Isaac Esparza Estrada, Roberto, Fierro-Rizo, Paola Flores Becerril, Clotilde Fuentes Orozco, Miguel García Castillo, Alejandro Gonzalez Ojeda, Ana Sofia Gonzalez Rubio, Erick Alonso González-García de Rojas, Luis Humberto Govea-Camacho, Jose Aldo Guzman Barba, Juan Carlos Ibarrola Peña, César Íñiguez Martínez, Francisco Javier Llamas-Macias, Ruben Eduardo Morán Galaviz, Cesar, Nuño-Escobar, Oscar-Everardo, Olvera-Flores, Jaqueline, Osuna-Rubio, Jose Victor Pérez-Navarro, Rodrigo, Prieto-Aldape, Luis Ricardo Ramirez Gonzalez, Marco Vinicio Ramírez Sánchez, Emilio, Reyes, Olaya Moramay Romero-Limón, Carlos Beas Ruiz-Velasco, José Antonio Sánchez Martínez, Guillermo, Sanchez-Villaseñor, Ismael, Sedano-Portillo, Gabriela Ambriz Gonzalez, Pedro Berrones Moreno Berrones Moreno, Ana Beatriz Calderon Alvarado, José de Jesús Cárdenas Barón, Araceli, Hernández, Francisco Javier León Frutos, Edgard Efren Lozada Hernandez, Eduardo Morales Valencia, Karla Daniela Pérez, Francina, Bolanos-Morales, Julio, Herrera-Zamora, Patricio, Santillan-Doherty, David Omar Arriaga Zavala, Salvador Francisco Campos Campos, Lizette, Carmona, Antonio Galindo Nava, Blanca, Santos, Juan Roberto Torres Cisneros, Katya, Bozada-Gutiérrez, Jose Jesus Herrera, Mucio Moreno Portillo, Francisco Pérez López, Mario, Trejo-Avila, Carlos Valenzuela Salazar, Maria Regina Alvarez, Fernando, Cordera, Marco Antonio de la Rosa Abaroa, Antonio, Gómez-Pedraza, Roberto, Hernandez, Antonio, Maffuz-Aziz, José Antonio Posada, Carlos Robles Vidal, Jose-Luis, Beristain-Hernandez, Blas Eduardo Quintero Sada, Nicolás Uxmal Soruco Heredia, Ernesto, Anaya, Ricardo, Arceo-Olaiz, Bernardo Gutiérrez Sougarret, Sonia Lopez Flores, Francisco, J Ochoa Carrillo, Raymundo Alfredo Pérez Uribe, Ludwigvan Adriano Bustamante Silva, Arianne, I Lupián-Angulo, Christian Enrique Soulé Martínez, Francisco César Becerra García, Ernesto Javier Guerrero Casillas, Edgar, Uribe, Nereida Esparza Arias, J Mindy Hernández-Nava, David, Isla-Ortiz, Javier, Melchor-Ruan, Esmeralda Romero Bañuelos, Rosa, Salcedo-Hernández, Diana, Vilar-Compte, Paola Zinser Peniche, Jorge, L Aguilar 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Sanchez Barrueco, Maria Dieguez López, Isabel López García, Pilar López-Toribio López, Marina, Bosch, Carolina Curtis Martínez, Alba Fernández Candela, Sandra Lario Pérez, Cristina Lillo García, Clara López de Lerma Martínez de Carneros, Francisco López Rodríguez-Arias, Inmaculada, Oller, Saray, Quinto, Luis, Sánchez-Guillén, Antonio Sanchís López, Álvaro, Soler-Silva, Daniel Triguero Cánovas, Victoria Garcia Peces, Estefania, Hernández-García, Guillermo, Plaza, Rafael Abad Alonso, Francisca Aranda Lozano, Marta Calvo Fernández, Eneko Del Pozo Andres, Josune Etxabe Gurrutxaga, Francisco Javier Fernández Pablos, Francisco Javier Ibáñez-Aguirre, Begoña Ochoa Villalabeitia, Natalia, Ortega, Amaia Sanz Larrainzar, Irune Vicente Rodriguez, Javier Jimenez Miramón, Jose, M Jover, Tamara, Llamero, Jose Luis Ramos Rodriguez, Ainhoa Valle Rubio, Maria Teresa Albiol, Codina, Antonio, Clara, Codony, Ramon Farres Coll, Cristina Farrés Pla, Nuria Gomez Romeu, Santiago, Lopez-Ben, Marcel, Pujadas, 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Marqueta De Salas, Paula Martinez Pascual, Almudena Ortiz Simón, Laura, Osuna, Marta Perez Gonzalez, Antonio Ramos Bonilla, Lorena Rodríguez Gómez, Jose Luis Uquillas, Miguel Angel Alonso Prieto, Marta, Ballesteros-Pomar, Sara Busto Suarez, Mario, Castaño, Laura Castillo Pardo, Mario De Arriba Alonso, Fernando Diez Burón, Anna Farrés Rabanal, Diego Fernández-Samos Fernández, David, Garcia, Cristina García Pérez, Miguel García Sanz, Cesar, Gracia, Javier, Gualis, Gonzalo Gutiérrez Carrillo, Mateo, Hevia, Eva Higuera Miguélez, Gregorio, Laguna, Cristina Lombardia Gonzalez de Lera, Pablo López Martínez, Pasquale, Maiorano, Sergio Marcos Contreras, Elio Martín Gutiérrez, Marta, Molina, Irene, Perez, Teresa Renedo Villar, Luis Angel Suarez Gonzalez, Eva Alvarez Torres, Luz Bueno Rey, Zulay Adriana Calderon Barajas, Ana, M Castaño-Leon, Aida, Fernández, Pablo Garcia Pimentel, Luis, Jimenez-Roldan, Meta, Levstek, Rosalia Navarro Casado, Claudia Olea Vielba, Ana Maria Parada Rodriguez, Igor, Paredes, Patricia, Pascual-Cambero, Miguel Saiz Sánchez-Buitrago, Claudia Sarrais Polo, Victor Zarza Fernandez de Alegria, Mireya, Bonet, Alberto Encinas Vicente, Jose Miguel Villacampa Auba, Maria Dolores Burgueño, Patricia Serrano Méndez, Thomas, W Jorgensen, Mercedes, Martin, Mónica, Huecas, Felipe, Velasco, Verónica Alen Villamayor, Santiago Alonso Bartolomé, Miguel Alonso Juarranz, Luis Felipe Ávila-Ramírez, Javier Buendia Pérez, Barbara, Burgos-Blasco, Enrique Camarero Rodríguez, Paula Campelos Fernández, Claudia, Celotti, Marco Ciappara Paniagua, Ignacio, Cristobal, Alejandro Encinas Bascones, Elena, Fernandez-Martin, Inés Gil Prados, Jesus Gimeno Hernandez, Maria Alejandra Giraldo, Manuel Gomez Cervantes, Noemi Guemes Villahoz, Araceli Hernández Ramos, Maria Cruz Iglesias Moreno, Bibiana Lasses Martínez, Francisco Leyva Rodríguez, Leyre López Antoñanzas, Javier Martín Monterrubio, Jose Maria Martinez-de-la-Casa, Lourdes Montero Cruces, Jesús Moreno Sierra, Jose Maria Muguerza, Alexia Victoria Paluso Montero, Natalia Pérez Romero, Adriana, Poch, Jaime Rodríguez de Alarcón, Adriana Ruano Campos, Rebeca Ruiz Roman, Patricia Saez Carlin, Cristina Sánchez Del Pueblo, Lidia Sotillo Valenzuela, Armando, Galvan, Miguel Ángel García Ureña, Enrique, González, Manuel Medina Pedrique, Alvaro Robin Valle de Lersundi, Carlos San Miguel, Juan, Aragón-Chamizo, Monica, Ballon, Jose, M Barrio, Beatriz Castro Catalan, Laura Cebolla Rojas, Renan Carlo Colombari, Miguel Cuende Diez, Paula Dujovne Lindenbaum, Oscar, Gil-de-Sagredo, Silvia Kayser Mata, Pablo Lozano Lominchar, Yeniffer Tatiana Moreno Salazar, Angela, Moreno-Gutierrez, Melanie, Morote, Uxue, Murgoitio, Nikolas Palma Caucig, Lucía Polanco Pujol, Alejandro, Prosperi, María Belén Ramírez Senent, Diego Fernando Ruiz Chiriboga, Mercedes, Sanz, Maria, Tudela, María Adrien Lara, Raquel, Alarza, Isabel Alonso Sebastian, Mariano Artés Caselles, Laura, Calles-Sastre, Marcos Casas Sánchez, Aritz Equisoain Azcona, Lucía, Fuentes, Lucia Gil Cidoncha, Sofía Herrero Gámiz, Eva Iglesias Garcia, Jose Luis Lucena De La Poza, Mª Eugenia Marín Martínez, Pilar Martín Rodrigo, Joaquin Manuel Muñoz Rodríguez, Verónica, Polaino, Alberto Pueyo Rabanal, Xabier Remirez Arriaga, Xiana, Rial, Miguel Sánchez Suárez, Maria Eugenia Torguet Muñoz, Borja Bazán Inostroza, Lara Blanco Terés, Alba Correa Bonito, Angela de la Hoz, Gustavo, Eisenberg, Javier Garcia Septiem, Jose Maria Lopesino, Rocio, Maqueda, Elena, Martin-Perez, Jose Luis Muñoz de Nova, Julia Revuelta Ramírez, Ana Rodríguez Sánchez, Álvaro Valdés de Anca, Laura Colao García, David Díaz Pérez, Enrique Esteban Agustí, Pablo Galindo Jara, Ana Belén Gallardo, Cesar, Garcia, Maria Gutierrez Samaniego, Miguel Angel Hernandez Bartolome, Lorenzo, Rabadan, Barriga Sánchez Raquel, Beatriz, Diéguez, Miguel, Hernández-García, Carolina Alfonso Carrillo, María Belén Alonso Bartolomé, Estibaliz, Alvarez, Mario, Alvarez-Gallego, Paula, Aragón-Ramos, Pablo Cesar Arteaga Asensio, Luis Asensio Gomez, Diego, Carrion, Nuria, Chavarrias, Alvaro de Arriba, Jose Antonio Gazo Martínez Gazo, Alberto Gegúndez Simón, Juan Gómez Rivas, Natalia Gonzalez Alcolea, Carolina, Gonzalez-Gomez, Sara Gortázar de Las Casas, María Alexandra Heras Garceau, Alicia Hernández Gutierrez, Luis, Lassaletta, Fuad Samir Lopez Fernández, Marta, Mancheño, Blanca, Mateos-Serrano, Isabel Pascual Miguelañez, Maria Fernanda Pedrero Escalas, Julio, Peñarrocha, Yolanda, Perez, Maria Isabel Prieto-Nieto, Teresa Rivera Schmitz, Laura, Rodrigáñez, Ines, Rubio-Perez, Isabel Sanchez Cuadrado, José Ignacio Sánchez Méndez, Jorge Fernando Tone, Carlos Toribio Vazquez, Aitor, Urbieta, Diego Córdova García, Francisca Garcia-Moreno Nisa, Laura, Jiménez, Inmaculada, Lasa, Belen, Matías-García, Fernando, Mendoza-Moreno, Marina Pérez González, Ana Sánchez Gollarte, Alejandro Sanchez Pellejero, Cristina Vera Mansilla, Rafael, Barberá, Lourdes, Montes-Jovellar, Sara Fra Fernández, Nicolas Moreno Mata, Barbara, Algar-Yañez, Gutiérrez, Bérénice, Olga De La Varga-Martínez, Paula, Fernandez-Valdes-Bango, Sandra Maria Gadin-Lopez, José María Martínez-Gómiz, Elena, Nieto-Moreno, Ana, Nieto-Moreno, Montserrat Ocampos Hernandez, Maria Laura Pelegrina-Lopez, Alicia Ruiz Escobar, Elena, Sáez-Ruiz, Beatriz, Vazquez-Rivero, Antonio, Lara, Belén Vielva Del Campo, Fernando Alcaide Matas, Simbad, Costas-Ochoa, José María García Pérez, Elizabeth, Marmol, Paula Troncoso Pereira, Maria Del Pilar Concejo Cutoli, Juan Ramón Gómez López, Juan Carlos Martín Del Olmo, Paloma Guillamot Ruano, Javier Páramo Zunzunegui, Antonio Albarracín Marín Blázquez, Alfonso, Aliaga-Sanchez, Marta María Arroyo Domingo, Miriam Artés Artés, Ana Isabel Avellaneda Camarena, Aida, Blaya, Emny Rochell Bobadilla Romero, Pedro Vicente Fernández-Fernández, Lorena Galindo Iñiguez, Víctor Javier García Porcel, Clara Giménez Francés, Antonio Javier Gomez Poveda, Rebeca Gonzalez Celdran, Francisco Miguel González Valverde, Laura Guillamon Vivancos, Elena, Gurrea-Almela, Alejandra Jara Maquilón, Jose David Jimenez Parra, Abd Al Aziz Lanagrán Torres, Raquel Lax Perez, Carmen Maria Lopez Lopez, Francisco, Machado, Alfonso Marco Garrido, Florencio Manuel Marin Martinez, Victoria Martínez Muñoz, Esther, Medina, Olimpia, Molina, José Manuel Muñoz Camarena, Julian, Onate, Pedro Antonio Parra Baños, Emilio Peña Ros, Enrique, Rubio, Marina Sánchez Robles, Carlos Sanchez Rodriguez, María Valero Soriano, María Teresa Yepes García, Felipe, Alconchel, Andrés Balaguer Román, Valentín, Cayuela, Ana, Conesa, Ana Delegido García, Pedro José Gil Vázquez, Paula Gómez Valles, Francisco, Gómez-Bosch, Vicente, J León-Muñoz, Francisco, Martínez, Alvaro, Navarro-Barrios, Tatiana, Nicolás-López, Pablo Ramirez Romero, Emiliano, Cano-Trigueros, María Concepcion Alonso González, Leticia Gómez Viana, Ana Pastor Zapata, Elisa Contreras Saiz, Tamara Díaz Vico, Maria, Fernandez-Hevia, Luis Joaquín García Flórez, Raquel, Rodríguez-Uria, Sandra, Sanz, Lorena, Solar-Garcia, Aida Suárez Sánchez, Jaume, Gelonch, Dietmar, Reinaldo, Miriam Abdulkarim Polo, Asier, Aguirre, Marta Alomar Bofill, Santiago, Baena, Ashish, Bartakke, Carmen Cabeza Oliver, Marta Castro Suárez, José Andrés Cifuentes Rodenas, Olga Claramonte Bellmunt, Ant Onia Crespí Mir, Anabel De La Llave Serralvo, Mar, Escales, Isabel Rosa Fernández Burgos, Pablo Gandia Gonzalez, Juan Lliteras Jorge, María Cristina Martínez Canto, Javier, Mata, Andreu, Morell, Naila, Pagès, Sara Pérez Palao, Cristian Plaza Valiente, Catalina Ramon Barcelo, Carmen Reyero Fernández, Albert Reyes Claret, Leticia Rodriguez Vaquero, Maialen Saez de Vicuña Salinas, Pilar Santos Cidon, Concepcion, Segura, Aina, Serra, Maria Serra Guivernau, Maria Soler Pedrola, Marta, Tasende, Marta Torrent Lluch, María Inmaculada Valldeperas Hernández, Rosa-Maria, Yañez-Lpez, Andrea, Craus-Miguel, Laura Fernández Vega, Natalia Pujol Cano, Juan José Segura-Sampedro, Laura Colet Oliver, Ivan Dot Pascuet, Mireia, Duart, Isabel Tello Galindo, Eduardo Arrea Salto, Jaume Cámara Cabrera, Marta Camats Terré, Juan Gabriel Castro Ríos, Marta de la Rosa-Estadella, Anna, Fernandez-Colorado, Anna, Gasulla-Rodriguez, Antonio, Gimenez-Gaibar, Elena, Gonzalez, Yeray Maldonado Sotoca, Matilde, Molina-Corbacho, Montserrat Monfort Mira, Josep, Rodoreda, Marta Santos Espí, Arnau Verdaguer Figuerola, Elisa Angela Diego-Alonso, Jaime, López-Sánchez, Luis, Muñoz-Bellvis, Jacobo, Trebol, Borja, Aguinagalde, Cristina Gabriela Alzate Arsuaga, Ainhoa Andres Imaz, Iñigo, Arana, Coro Aranzabal Urrutia, Mikel, Armendariz, Lorena, Arrabal, Iñigo, Augusto, Adolfo, Beguiristain, Laura, Busto, Ainhoa, Cuevas, Itziar De Ariño, Alejandro, Elúa, Leticia, Fernandez, Arantza, Fernandez-Monge, Lander, Gallego, Alba, Garcia, Amaia Garcia Dominguez, Gregorio, Garmendia, Carmen, Grañén, Pelayo Hevia Rodríguez, Maria, Iraola, José Miguel Izquierdo, Aintzane, Lizarazu, Jon Ander Lizarbe, Claudia Cristina Lopes Moreira, Iker, López, Ruth Marquina González, Tania, Pastor, Adrián Recio Ayesa, Ana Paula Riverola Aso, Carballo, Rodríguez, Araceli, Rodrìguez, Maria Inmaculada Ruiz Montesinos, Patricia, Torres, Jose, Undabeitia, Ainara, Villafruela, Maria Barrionuevo Ramos, David, Blanco, Marta, Calderón, Eva Corral Rubio, Angel, Cuadrado-García, Daniela, Cubek, Ignacio, Fariña, Maria Fernandez LLorente, Natalia Flores Amador, Mariana García Virosta, Luis Garcia-Sancho Tellez, Adelina Gonzalez Martinez, María, Hernandez, Rubén Herreros Ruiz-Valdepeñas, Carmen Jimenez Sanchez, Eduardo Llamazares Cobo, María, López, Javier, López-Martin, Teresa Martínez Marivela, Luis Miguel Martinez Parra, Paloma Maté Mate, Paloma, Medrano, Manuel Moriche Carretero, Sara Núñez O'Sullivan, Manuel Ortega Oria de Rueda, María Begoña Pastor Nieto, Clara, Pérez, Antonio, L Picardo, Remedios Revilla Amores, Carmen Rodríguez Haro, Jose Alberto Rojo López, Fatima Sanchez Cabezudo Noguera, Cristina, Sanz, Daniel Serralta de Colsa, Cristina Valor Garcia, Marta Velasco Martinez, Iván Andújar Lara, Aranzazu, Calero-Lillo, Enrique, López-Ruiz, Alberto Díaz García, Alejandro Menéndez Moreno, Luis Eduardo Pérez-Sánchez, Ángela, Pascual, Miguel Adeba García, Marta Alonso Fernández, Javier Alvarez Gama, Roberto, Ballestero, Loreto Berjon De La Vega, Paola Calleja Hermosa, Mariana, Carrillo-Rivas, Alfonso, Casado, Andrea, Cerveró, Bonifacio Cimadevilla Calvo, Patricia Corriols Noval, Paloma de la Dehesa Cueto-Felgueroso, Miren Jasone Diez Zapirain, José Estevez Tesouro, José Antonio Fernández-Dívar Sánchez, Lucia Garcia Alcalde, Juan García Cardo, Tito García Moreno, Daniel, García-López, Belen Garcia-Montesinos Perea, Miren Gonzalez Benito, Rocio, Gonzalez-Aguado, Miguel Ángel Gordo Vega Gordo-Vega, Jose, Gutierrez-Banos, Jaime Jimeno Fraile, Yolanda Jubete Castañeda, Patricia Lopez Gomez, Antonia Jesús López López, David Mato Mañas, Carmelo, Morales-Angulo, Dieter, Morales-Garcia, Sara, Naranjo, Jose Luis Rabago, Jose Manuel Rabanal, Rocio Revuelta Zorrilla, Adriana Reyes Echeverría, Juan Carlos Rodríguez-Sanjuán, Juan Ramón Sanz, Isabel Simal Badiola, Guillermo, Tejón, Enrique Toledo Martínez, Raquel Varea Malo, Begoña, Fadrique, Tania, Funes, Elena González Revilla, Isaias, Alarcón, Daniel Aparicio Sánchez, Pablo Beltran Miranda, Carmen, Cepeda-Franco, María Josefa Cuevas López, Sandra, Dios-Barbeito, Virginia María Durán Muñoz-Cruzado, Carlos Gonzalez De Pedro, Rosa, M Jimenez-Rodriguez, Francisco, Manresa-Manresa, Gabriel, Marin, Cristobalina, Martin-Garcia, Sara, Martínez-Núñez, Juan Manuel Martos Martinez, Lucas, Mengíbar, Felipe Pareja Ciuro, Eduardo Perea Del Pozo, Veronica Pino Diaz, José, Pintor-Tortolero, Claudia, Quintero-Pérez, Maria Luisa Reyes Diaz, Mercedes Rubio Manzanares Dorado, Alejandro Sanchez Arteaga, Ana, Senent-Boza, Luis, Tallon-Aguilar, Jose, Tinoco-Gonzalez, Luis-Cristobal, Capitan-Morales, Juan Cintas Catena, Javier, Valdes-Hernandez, María Del Campo Lavilla, Alina López De Fernández, Miriam Abellan Lucas, Alba Diaz Padillo, Maria Gómez Romero, Linda Grace Puerto Tamayo, El Mostafa El Yaqine Er Raoudi, Melody García Domínguez, María Ángeles Gascón Domínguez, Marta González Pérez, Alba Hernáez Arzoz, Joana San Anton, Cristian, Ruminot, Hander Guillermo Acosta Diaz, Daniella, Laguado, Kristina, Aghababyan, Alba, Jr, Enrique, Artigues, Rocío, Belda, Miguel, Beltran, Jose Ignacio Blanes, Elena Campos Carot, Miriam, Cantos, Laura, Costa, Carolina Ferrer Gomez, José María Gallego Sánchez, Oscar, Gil-Albarova, Juan, Gilabert-Estellés, Emilio Lopez Alcina, Isabel López Sánchez, Severiano Marin Bertolin, Carolina, Martinez-Perez, Antonio Melero Abellán, Claudia Mulas Fernández, Beatriz, Novoa, Ruth, Nuñez, Pablo Renovell Ferrer, Guijarro-Jorge, Ricardo, Carolina Soledad Romero Garcia, Miguel Sanfeliu Giner, Silvia, M West, Enrique, Zapater, Ignacio, Miranda, Ana, Monís, Alejandro Roselló Añón, María José Sangüesa, Jorge Sanz Romera, Marcos, Adrianzén, Maria Barrios Carvajal, Mireia, Bauzá, Ana Benítez Riesco, Jose Antonio Carbonell Lopez, María-Carmen, Fernández-Moreno, Ricardo Gadea Mateo, Francisco, Garcia, Maris Luisa García-Pérez, Luisa Paola Garzon, Ana, Izquierdo, Maria Lapeña Rodríguez, Carlos, León-Espinoza, Fernando, Lopez, Rosa Martí Fernández, Sara Martínez Castro, Berta Monleón López, Isabel Mora Oliver, David, Moro-Valdezate, Ernesto Muñoz Sornosa, Sara Palomares Casasús, Leticia Pérez Santiago, Mara Albert Fort, Reyes, Balanzá, Lorena Bermell Marco, Carla Carratalá Pérez, Claudia Pilar Clemente Tomas, Marta, Córcoles, Jose Ángel Diez Ares, Carlos Domingo Del Pozo, Nuria Estellés Vidagany, Gonzalo, Garrigos, Mar Gimeno Gimeno Vicente, Blanca Alastrue Giner, Segundo, Gomez-Abril, Paloma, Gonzalez, Paula Gonzálvez Guardiola, Guillermo Sebastian Martínez Fernández, Charo Martínez García, Lucía, Martínez-Costa, Luz María Moratalla Charcos, Sergio Navarro Martínez, Carmen, Payá-Llorente, Álvaro Pérez Rubio, Nuria, Peris, Eduardo Picazo Pineda, Jordi Planelles Gómez, Francisco Ripoll Vidal, Andrea, Roca, Enrique, Salmerón-González, Raquel Segura Roselló, Ramon Trullenque Juan, Cristina Verdejo Gimeno, Jose Miguel Zaragozá García, Gema Zomeño Bravo, Marcos Bruna Esteban, Hanna, Cholewa, Milton de Jesus, Matteo, Frasson, Luis Oliver García, Héctor, J Aguado, Antonio Jose Alonso Villalba, Francisco, Ardura, Carmen Elena Badillo Bercebal, María Bedate Núnez, Alvarez-Ramos Begoña Aranzazu, Juan Beltrán de Heredia, Hugo, Bermejo, Juan Berrocal Cuadrado, Maria Bragado González, Juan, Bustamante-Munguira, Raul Calvo Gonzalez, Yolanda, Carrascal, Ana Belén Casas Marcos, María Carmen Cervera, Sergio Chávez Valladares, Ángel Cilleruelo Ramos, Susana, Cortes, Jesús, Crespo-Sanjuán, María, Cuaresma, Luis Antonio Cuellar Martin, Carlos Ferreras García, Alvaro, Fuentes-Martín, Abel, Ganso, Elena García García, Luis, Garcia-Florez, Virginia, Garcia-Virto, Juan, Gatón, Julio Alberto Gobernado Tejedor, Tania Gómez Sanz, Jose Ignacio González Martín, María Begoña Gregorio Crespo, Ana Herranz Arriero, Jose, Herreros, Marta Ibáñez Nieto, César, Infante, Carlos, Jezieniecki, Moises, Juarez, Gregorio de Jesus Labrador Hernandez, Ana Patricia Legido Morán, Ricardo León Fernández, Alejandro, Leon-Andrino, Almudena, Llorente, Maria Lopez Pais, Mauricio Loucel Bellino, Sergio, Martin, Miguel Angel Martin-Ferrero, Gonzalo Martinez Municio, Elvira Mateos Alvarez, José María Matilla, Luis María Merino Peñacoba, Mario, Montes-Manrique, Fernando Natal Álvarez, David, C Noriega, Henar Nuñez Del Barrio, Francisco Javier Ortiz de Solórzano Aurusa, Lucía, Pañeda, Victoria Pascual Escudero, Miguel Pascual Samaniego, Adela, Pereda, Marta Pérez Febles, Laura, Pesquera, Maria, Plata, Emma Puertas Ruiz, Mario, Rodriguez-Lopez, Alejandro Romero de Diego, Ana, Ruano, María Ruiz Soriano, Cristina Sánchez Torralvo, Silvia Santiago Maniega, Bárbara, Segura-Méndez, Clarisa Simon Perez, José, Soro-García, Paula Suárez Mansilla Suárez-Mansilla, Jeancarlos Trujillo Díaz, Mª Esther Valsero Herguedas, Andrea Vazquez Fernandez, Eduardo Velasco García, Ana, Zabalza, Álvaro Zamora Horcajada, Fernando Acebes García, Enrique Asensio Díaz, Martín, Bailón, Alejandro David Bueno Cañones, Alvaro Centeno Velasco, Ekta Choolani Bhojwani, Fernando Labarga Rodríguez, Sara, Mambrilla, Pablo, Marcos-Santos, Toledano, Miguel, David Pacheco Sánchez, Baltasar, Pérez-Saborido, Pilar, Pinto, Katherine, Plua, Javier Sanchez Gonzalez, Vicente, Simo, Rosalía Velasco López, Sandra Veleda Belanche, Fabiola Eugenia Michel Campos, Iciar Muñoz Lindez, Maria, Balluerca, Maite, Camuera, Pablo, Helguera, Imanol, Herrero, Patricia Paunero Vazquez, María, Sánchez-Rubio, Isami, Soeda, María Dolores Arribas Del Amo, Vicente Manuel Borrego Estella, Estefania, Casas, Néstor Castán Villanueva, Daniel Delfau Lafuente, Elena Delgado Blanco, María, Domingo, Ismael Gil Romea, Azucena, Gonzalo, Emilio Lagunas Lostao, Noelia Lete Aguirre, Yaiza Martinez Lahoz, Jesús Víctor Pérez-Tierra Ruiz, Maria Del Mar Soriano, Isabel Valero Lázaro, Esmeralda Carnicer Escusol, Guillermo Pola Bandres, Juan Luis Blas Laina, Beatriz, Cros, Patricio Andrés Freile Pazmiño, David, Garcia-Aguilera, Ana Mejía Casado, Ana, Nogués, Issa Talal El-Abur, Carlos, Yánez, Isabel Gascon Ferrer, Carlos, Gracia-Roche, Ursula María Jariod Ferrer, María Victoria Simón Sanz, Tomas, Uson, Waseem, Ahamed, Sumudu, Jayasinghe, Eranda, Karunadasa, Prathibha, Nelihela, Sujeewa Priyantha Bandara Thalgaspitiya, Dickson, Wickramarathna, Nagenthiram, Harivallavan, Pirashanthan, Nagarasa, Eranga, Perera, Kanapathipillai, Piratheep, Vithranage Srimantha Dewsiri Rodrigo, Meera, Thayalan, Rajendram, Thayaparren, Arulprashanth, Arulanantham, Kanishka De Silva, Gagana, Ganga, Anuja Nadeeshan Kumarasinghe, Mahanada, Udukala, Koculen, Vimaleswaran, Prashanthan, Yogarajah, Ravindri, Jayasinghe, Probhodana, Ranaweera, Mohamed, Rishard, Dharmabandhu, N Samarasekera, Sanjeewa, Seneviratne, Sivasuriya, Sivaganesh, Chamal, Fernando, Nishantha, Mendis, Balasingam, Balagobi, Balasupramaniam, Sathesan, Lanka, Dasanayake, Malitha, Patabendige, Wickramasooriya, Dj, Kugarajh, Ganeshapillai, Sathyamoorthy, Prasanna, Dileepa, Ediriweera, Sumudu, Kumarage, Asanka, Jayawardane, Athula, Kaluarachchi, Pituwala Liyanage Adithya Sirisena, Abubakr, Abubakr, Hozifa, Mohamed, Ismail, Mustafa, Mogahid, Sharfeldein, Samir, Ismail, Reem, Musa, Monira, Sarih, Mussab, Abaker, Eman Adam Abdalla, Mohamad, Abdelbagi, Alsafe, Adlan, Ahmed, Alnaeem, Safa, Atyah, Yasir, Awad, Rsheeda, Dawelbait, Mohamed El Hag, Ibrahim, Elbashir, Sami, Eldirdiri, Samwal, Eldirdiri, Mohammed Eltahier Abdalla Omer, Lana Abdalgadir Ahmed Mohamed, Hiba Hassan Rehmtallah Ahmed, Mohammed Balla Yousif Balla, Abdulmoiz, Aljafari, Abdulmalek, Aljafari, Elsagad, Mohamed, Abdulkader, Mohammad, Abdulkader, Shaar, Mohamed Nafea Shaar, Maab Hussein Yousif Elhafiz, Mohammed Husien Yosif Elhafiz, Abubakr Ali Mohammed Alhassan Humidan, Almigdad, Ali, Hisham, Eljack, Mohamedyasin, Elrashid, Manhal, Ahmed, Albrra, Alhag, Douaa, Ali, Mohammed Ahmed Babikir, Imad, Bakheit, Hytham K, S Hamid, Sami, Mohamed, Walid, Shaban, Nidhal, Siddig, Mohamed, Suliman, Rihab Yasir Abdelmagid, Abubaker, Yassin, Omer, Abbas, Eltahir, Abdelrahim, Muhammed, Ahmed, Mohamed, Elobaid, Adil, Hashim, Ali, Mohamed, Omer, Mohamed, Khalid, Osman, Abdallah, Yousif, Safaa, Abdulaal, Marwa, Elsadig, Mohammed, Hussain, Malaz Amir Ataalmanan, Doha Amir AtaAlmanan, Tebyan Amir AtaAlmanan, Alaa, Elgaili, Maria, Mohamed, Usra, Omara, Alkhansa, Osman, Amna, Osman, Safaa, Saad, Abdelkareem, Ahmed, Ali Adil Ali Karar, Aya, Alhassan, Mohanad, Alsidig, Mohamed, Eljack, Mohammed Ibrahim Mohammed Ali, Awad Kamal Awad Osman, Liena, Mohamed, Samah Ibrahim Omer Mohamed Osman Mohamed Osman, Altayeb, Mohammed, Ayman, Mohammed, Khadija, Muhmmed, Eltahir, Musa, Egbal Sahal Abdelmajed, Khalid Z M, Y Hamid, Omnia M, M Yousif, Mahmoud, Saleh, Osman, Bashir, Yassein, Elhussein, Omar, Madani, Eva, Angenete, Jennifer, Park, Lars, Gillberg, Monir, Jawad, Linas, Pieteris, Yousif, Saeed, Sergej, Safonov, Martin, Spångfors, Henrik, Andersson, Hans, Bahlmann, Karin Björnström Karlsson, Michelle, Chew, Lara, Daham, Lina De Geer, Helen, Didriksson, Gunilla, Gagnö, Carina, Jonsson, Anna, Oscarsson, Pamela, Buchwald, Mathilde, Delorme, Marie-Louise, Lydrup, Shahin, Mohseni, Arvid, Pourlotfi, Souheil, Reda, Kajsa, Anderin, Nina, Blomme, Josefin, Segelman, Malin, Simlund, Anders, Thorell, Fredrik, Wogensen, Daniel, Danielsson, Peter, Elbe, Rebecka, Hultgren, Boel, Hynning, Fredrik, Klevebro, Karin, Lind, Ebba, K Lindqvist, Carl, Montan, Ernesto, Sparrelid, Clara Svenberg Lind, Jeremy, Wales, Andreas, Älgå, Martin, Nordberg, Emil, Pieniowski, Ioannis, Gkekas, Niklas, Löfgren, Karolina, Niska, Robert, Zürner, Silvio, Däster, Otto, Kollmar, Savas, Soysal, Stephanie, Taha-Mehlitz, Athanasios, Tampakis, Dominik Valentin Flury, Marie, Heyne-Pietschmann, 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Travis, Grotz, James, Jakub, Rahul, Kanade, David, Larson, Sherief, Shawki, Dennis, Wigle, Haradeen, Dhillon, Avni, Suri, Leonardo Weber Graeff, Ahmed, Elshabrawy, Grace Ihsiu Todd, Mark, Davies, Yan, Qi, Walter, Biffl, Kathryn, Schaffer, Sarah, Averbach, Terry, Curry, Alexandra, Schwartz, Mary Kathryn Abel, Veronica, Andaya, Kristina, Benirschke, Katherine, Bigay, Marissa, Boeck, Lee-Lynn, Chen, Lee-May, Chen, Huey-Lan, Chern, Amanda, Compadre, Patricia, Conroy, Alexa, Glencer, Patrick, Ha, Barbara Cs Hamilton, Johannes, R Kratz, Rondall, Lane, Rex, H Lee, Brenda, Nunez-Garcia, Richard, O'Donnell, Doruk, Ozgediz, Paul, Park, Ankit, Sarin, Ipsit, Shah, Bonnie, Sheu, Madhulika, Varma, Katherine, Wai, Rosanna, Wustrack, Mary Jue Xu, Melissa, Zimel, Pedro, Escobar, Meredid Maldonado Santiago, Mohammad, Azam, Asad, Choudhry, Eric, Hammond, William, Marx, Jihad, Abbas, Somya, Al-Embideen, Carol, Angel, Bailea, Bobich, Raul, Bosio, Gregory, Georgiadis, Tahir, Jamil, Maria, Kenner, Meghan, Lark, Tamara, Maghathe, Sonia, Masih, Gabriel, Naimy, Kristin, O'Mara-Gardner, Emily, Rady, Roberta, Redfern, Jack, Sample, Joseph, Sferra, Kaitlyn, Sharp, Jessica, Shoemaker, Stephen, Stanek, John, Stengle, Hibba, Sumra, Jeffrey, M Sutton, Faris, Azar, Anne, Fischer, Jaymie, Henry, Lawrence, Lottenberg, Mario, Rueda, Sasha, Thiel, Adel, Bozorgzadeh, John, Kelly, Armando Salim Munoz Abraham, Erin, Scott, Camila, Haro, Andrés, Pouy, Gastón, Acuña, Sofia, Álvarez, Ana Carmen Carbajal, Fabiola, Castedo, Diego, Pereiranuñez, Helena, Sobrero, Josefina, Tarigo, Rafat, Al-Saban, Fatima, Al-Eryani, Siham Al Maqtari, Sahar, Al-Maqtari, Mahmmoud, Abdualqader, Majed, Aeed, Ghadeer Al Sanany, Anwaar Al Dhafif, Buthina Al Jarmozi, Saba, Al-Ameri, Awsan, Al-Dhaheri, Dhyia Alhuq Al-Surimi, Amira, Alakhdury, Sabreen, Alashmali, Zainab, Alattas, Manar, Alduba'Ai, Hamdan, Aldumaini, Wafa, Alhaddad, Abdelrahman, Alharazi, Nawal, Alhemyari, Adnan, Alhumaida, Maniee, Aljabri, Hassan, Almarashi, Zuhoor, Almohanady, Marwa, Alodine, Nooraldin, Alqasemi, Basma, Alqudaimi, Ansam Mohammed Ghaleb Alrobaiee, Mohammed, Alsabri, Radfan, Alsalal, Ramzi, Alsayadi, Musaed, Alsayadi, Reem, Alshaipani, Ebrahim, Alsharabi, Nora, Atiah, Hadeel, Bajjah, Muhib, Esmael, Asma, Ghallab, Rana, Ghannam, Adwa'A, Hamid, Lina, Hashem, Sara, Saif, Shaima, Sayad, Nawras, Shaban, Amatallah Hadi Shamsan, Sarah, Shream, Amal, Shukri, Shahd, Zeid, Nabila, Abdullah, Abdulrahman Faisal Al-Garadi, Ahmed, M Ali Al-Radhi, Norhan, Naji, Shaima'A, Nasser, Areej Taha Al Anaib, Ebrahim, Abdurab, Fadhl Al Muhtadi, Amer, Al-Hebbah, Ahmed, Al-Madhrahi, Shehab, Al-Mahdi, Sakhr Abdulhakeem Al-Maswari, Ayman, Al-Oqabi, Zakarya Abdullah Al-Zaazaai, Karim, Al-Zazay, Ali, Alafif, Asem, Albzzaz, Lina, Alqalisi, Mohammed, Alrezami, Haneen, Alshargabi, Mokhtar, Alshargabi, Hossam, Ghanem, Kareem, Saeed, Rasheed, Shalabi, Fareed, Showqi, Miriam, Maimbo, Catherine, Mkandawire, Mulaya, Mubambe, Theresa, Nkole, Vanessa, Savopoulos, Patricia, Shinondo, Chabwera, Shumba, Penias, Tembo, Shelton, Chivanga, Ngqabutho, Dube, Handsome, Dube, Daniel, Dzinotyiwei, Ronald, Makanda, Moses, Mangena, Partson, Maphosa, Derek, Matsika, Proud, Mawere, Nkosikhona, Moyo, Assel, Moyo, Arnold, Muguwu, Simbarashe, Mungazi, Garikai, Mwale, Gamuchirai, Ndabvonga, Mambote Crispin Olivier Ntoto, Hardlife, Ranganai, Ernesto Sánchez Castillo, Oltah, Tshuma, Grace, Gwini, Vimbai Moyana Muguto, Gilbert, Moyo, Trust, Mushawarima, Tinashe, Shoko, Rorisang, Jamela, Marvellous, Machiri, Eric, Shumba, Antony, Chengahomwe, Yemurai, Bikwa, Maxwell, Chimhina, Jeremy, Marume, Kudzayi, Munanzvi, Precious G, T Mutambanengwe, Federico, Ferrari, Marco, Fontanella, Franco, Odicino, Romano, Vito, Nepogodiev D, Emanuele Cammarata, Sofia Campanella, Daniela Canzonieri, Adriana Cordova, Federico De Michele, Ettore Dinoto, Mara Franza, Leo Licari, Daniele Matta, Domenico Mirabella, Felice Pecoraro, Roberto Pirrello, Pierfrancesco Pugliese, Fernando Rosatti, Giuseppe Salamone, Francesca Toia, Massimiliano Tripoli, Nepogodiev, D, Rosati, R, Surgery, Medicine and Pharmacy academic/administration, Basic (bio-) Medical Sciences, Surgical clinical sciences, Faculty of Medicine and Pharmacy, Gastroenterology, Medical Oncology, Clinical sciences, Breda, João, ARD - Amsterdam Reproduction and Development, Paediatric Surgery, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, AGEM - Endocrinology, metabolism and nutrition, Graduate School, Tytgat Institute for Liver and Intestinal Research, Laura Alberici, Filippo Antonacci, Alessandro Arena, Angela Belvedere, Fabio Bernagozzi, Paolo Bernante, Pietro Bertoglio, Lorenzo Bianchi, Maria Bisulli, Barbara Bonfanti, Safia Boussedra, Jury Brandolini, Crescenzo Cacciapuoti, Stefano Cardelli, Riccardo Casadei, Matteo Cescon, Alessandro Cipolli, Riccardo Cipriani, Alfredo Conti, Luca Contu, Francesco Costa, Niccolo’ Daddi, Eugenia De Crescenzo, Pierandrea De Iaco, Alessandra De Palma, Massimo Del Gaudio, Anna Nunzia Della Gatta, Giampiero Dolci, Giulia Dondi, Matteo Droghetti, Sergio Nicola Forti Parri, Elena Garelli, Chiara Gelati, Giuliana Germinario, Federico A. Giorgini, Carlo Ingaldi, Elio Jovine, Kenji Kawamukai, Antonio Lanci Lanci, Raffaele Lombardi, Maria Elisa Lozano Miralles, Claudio Marchetti, Michele Masetti, Francesco Minni, Daniele Morezzi, Daniele Parlanti, Alice Pellegrini, Anna Myriam Perrone, Anna paola Pezzuto, Marco Pignatti, Gianluigi Pilu, Valentina Pinto, Gilberto Poggioli, Silvana Bernadetta Puglisi, Diego Raimondo, Matteo Ravaioli, Claudio Ricci, Sara Ricciardi, Francesco Ricotta, Roberta Rizzo, Angela Romano, Matteo Rottoli, Riccardo Schiavina, Renato Seracchioli, Matteo Serenari, Margherita Serra, Piergiorgio Solli, Gioia Sorbi, Mario Taffurelli, Marta Tanzanu, Achille Tarsitano, Marco Tesei, Gabriele Vago, Tommaso Violante, Simone Zanotti, Tommaso Frisoni, leonardo solaini, giorgio ercolani, Fruscio, R, Ornaghi, S, Collaborative, Covidsurg, Collaborative, Globalsurg, Palmisano, Silvia, de Manzini, Nicolo', Žundienė, Laura, Dulskas, Audrius, Kuliavas, Justas, Čekauskas, Albertas, Kielaitė-Gulla, Aistė, Poškus, Tomas, Strupas, Kęstutis, Želvys, Arūnas, COVIDSurg Collaborative, GlobalSurg Collaborative, Department of Surgery, HUS Abdominal Center, Simoes, Jff, Li, E, Picciochi, M, Glasbey, Jc, Baiocchi, G, Blanco-Colino, R, Chaudhry, D, Alameer, E, El-Boghdadly, K, Wuraola, F, Ghosh, D, Gujjuri, Rr, Harrison, Em, Lule, H, Kaafarani, H, Khosravi, M, Kronberger, I, Leventoglu, S, Mann, H, Mclean, Ka, Mengistu, Gm, Modolo, Mm, Ntirenganya, F, Norman, L, Outani, O, Pius, R, Pockney, P, Qureshi, Au, Roslani, Ac, Satoi, S, Shaw, C, Bhangu, A, Omar, Om, Ahmed, Wur, Argus, L, Ball, A, Bywater, Ep, Brar, A, Dawson, Be, Duran, I, Elhadi, M, Jones, C, Kamarajah, Sk, Keatley, Jm, Lawday, S, Marson, Ej, Ots, R, Santos, I, Taylor, Eh, Trout, Im, Varghese, C, Venn, Ml, Xu, W, Dajti, I, Gjata, A, Kacimi, Seo, Boccalatte, L, Cox, D, Townend, P, Aigner, F, Kronberger, Ie, Samadov, E, Alderazi, A, Hossain, K, Padmore, G, van Ramshorst, G, Lawani, I, Cerovac, A, Delibegovic, S, Gomes, Gma, Buarque, Il, Gohar, M, Slavchev, M, Nwegbu, C, Agarwal, A, Martin, J, Ng-Kamstra, J, Olivos, M, Lou, Wh, Ren, Dl, Calvache, Ja, Rivera, Cjp, Hadzibegovic, Ad, Kopjar, T, Mihanovic, J, Jimenez, Pma, Gouvas, N, Klat, J, Novysedlak, R, Amisi, N, Christensen, P, El-Hussuna, A, Batista, S, Lincango-Naranjo, E, Emile, S, Sandoval, Daa, Dhufera, H, Hailu, S, Mengesha, Mg, Kauppila, Jh, Arnaud, Ap, Demetrashvili, Z, Albertsmeier, M, Lederhuber, H, Loffler, Mw, Acquah, Dk, Ofori, B, Tabiri, S, Metallidis, S, Tsoulfas, G, Aguilera-Arevalo, Ml, Recinos, G, Mersich, T, Wettstein, D, Kembuan, G, Milan, Pb, Khosravi, Mh, Mozafari, M, Hilmi, A, Mohan, H, Zmora, O, Gallo, G, Pata, F, Pellino, G, Fujimoto, Y, Kuroda, N, Abou Chaar, Mk, Ayasra, F, Fakhradiyev, I, Hamdun, Ih, Jin-Young, J, Jamal, M, Karout, L, Gulla, A, Rasoaherinomenjanahary, F, Samison, Lh, Sanchez, Iid, Gonzalez, D, Martinez, L, Martinez, Mj, Nayen, A, and Ramos-De la Medina, A
Subjects: Male, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], MULTICENTER, infectious diseases, 0302 clinical medicine, 030202 anesthesiology, Anesthesiology, Cirugía, 80 and over, Prospective Studies, Young adult, Child, Lung, Aged, 80 and over, COVID-19, delay, SARS-CoV-2, surgery, timing, SARS‐CoV‐2 infection, Operative, Child, Preschool, Pneumonia & Influenza, Infection, Cohort study, Human, medicine.medical_specialty, Clinical Sciences, Sars-cov-2, GlobalSurg Collaborative, Settore MED/28 - MALATTIE ODONTOSTOMATOLOGICHE, 03 medical and health sciences, Clinical Research, Biodefense, Correspondence, Humans, PULMONARY COMPLICATIONS, CRIANÇAS EM IDADE PRÉ-ESCOLAR, Aged, Science & Technology, Cirurgia, Prevention, Infant, Odds ratio, Pneumonia, Prospective Studie, Clinical research, Surgery, Human medicine, 610 Medizin und Gesundheit, 1109 Neurosciences, Internationality, Settore MED/29 - CHIRURGIA MAXILLOFACCIALE, Settore MED/18 - CHIRURGIA GENERALE, Adolescent, Adult, Cohort Studies, Female, Middle Aged, Surgical Procedures, Operative, Time, Young Adult, Practice Guidelines as Topic, gastroenterology, Medicine and Health Sciences, 030212 general & internal medicine, Prospective cohort study, Mortality rate, Covid19, Infectious Diseases, Patient Safety, medicine.symptom, 6.4 Surgery, Life Sciences & Biomedicine, 610 Medicine & health, COVID-19, SARS-CoV-2, delay, surgery, timing, Asymptomatic, NO, COVIDSurg Collaborative, Vaccine Related, All institutes and research themes of the Radboud University Medical Center, medicine, Mortalitat, ddc:610, Mortality, Preschool, LS7_4, Surgical Procedures, business.industry, Neurosciences, Evaluation of treatments and therapeutic interventions, 1103 Clinical Sciences, 3126 Surgery, anesthesiology, intensive care, radiology, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Anesthesiology and Pain Medicine, Emerging Infectious Diseases, Good Health and Well Being, Mortalidad, Cohort Studie, business
Abstract: Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay. ispartof: ANAESTHESIA vol:76 issue:6 pages:748-758 ispartof: location:England status: published
Published: 2021

23. Siglec-7 is a predictive biomarker for the efficacy of cancer vaccination against metastatic colorectal cancer

Author: Yuki Nakagami, Hiroo Kawano, Tomio Ueno, Nobuaki Suzuki, Yoshinobu Hoshii, Michihisa Iida, Hiroyuki Ogihara, Satoshi Matsukuma, Yoshihiko Hamamoto, Shoichi Hazama, Shigeru Takeda, Kensuke Yamada, Tomonobu Fujita, Yukio Tokumitsu, Hiroaki Nagano, Nobuyuki Fujiwara, Yusaku Watanabe, Hiroto Matsui, Yoshitaro Shindo, Shinobu Tomochika, Shin Yoshida, Tatsuya Ioka, Yutaka Kawakami, Ryouichi Tsunedomi, Ming Xu, and Shinsuke Kanekiyo
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, colorectal cancer, 03 medical and health sciences, 0302 clinical medicine, Cancer immunotherapy, sialic acid-binding immunoglobulin type lectin-7, Internal medicine, medicine, peptide vaccine, biology, Oncogene, business.industry, Cancer, Immunotherapy, Articles, respiratory system, medicine.disease, Molecular medicine, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Biomarker (medicine), biomarker, protein expression analysis, Antibody, business
Abstract: Cancer immunotherapy, including vaccination, is considered a major scientific and medical breakthrough. However, cancer immunotherapy does not result in durable objective responses against colorectal cancer (CRC). To improve the efficacy of immunotherapy, the present study investigated several biomarkers for selecting patients who were expected to respond well to immunotherapy. Firstly, a comprehensive proteomic analysis was performed using tumor tissue lysates from patients enrolled in a phase II study, in which five human leukocyte antigen (HLA)-A*24:02-restricted peptides were administered. Sialic acid-binding immunoglobulin type lectin (Siglec)-7 was identified as a potential predictive biomarker. Subsequently, this biomarker was validated using western blot analysis, and immunofluorescence using tissue samples from the patients enrolled in the phase II study. The expression levels of Siglec-7 detected by immunofluorescence were quantified and their association with overall survival (OS) in patients treated with the peptide vaccine was examined. Furthermore, considering the important role of tumor-infiltrating lymphocytes (TILs) for CRC prognosis, the densities of CD3+, CD4+, CD8+ and forkhead box P3 (FOXP3)+ T cells in CRC tissues were examined and compared with Siglec-7 expression. The mean expression levels of Siglec-7 were significantly higher in patients with poor prognosis, with an OS of ≤2 years, as shown in comprehensive proteomic analysis (P=0.016) and western blot analysis (P=0.025). Immunofluorescence analysis demonstrated that Siglec-7 was expressed in intratumoral macrophages. The OS in patients with high Siglec-7 expression was significantly shorter than in that in patients with low Siglec-7 expression (P=0.017) in the HLA-A*24:02-matched patients. However, this difference was not observed in the HLA-unmatched patients. There was no significant difference in OS between patients according to the numbers of TILs, nor significant correlation between TILs and Siglec-7 expression. In conclusion, Siglec-7 expression in macrophages in tumor tissue may be a novel predictive biomarker for the efficacy of immunotherapy against metastatic CRC.
Published: 2020

24. Laparoscopic treatment of median arcuate ligament syndrome in a 16-year-old male

Author: Shumei Mineta, Michi Ueno, Yoshinori Fujiwara, Tomio Ueno, Hiroaki Kusunoki, Toshimasa Okada, Masaharu Higashida, Mio Uraoka, Atsushi Tsuruta, Yusakua Watanabe, Yuko Okamoto, and Hisako Kubota
Subjects: medicine.medical_specialty, Decompression, MALS, median arcuate ligament syndrome, Median arcuate ligament syndrome, Celiac plexus, Laparoscopic approach, 030204 cardiovascular system & hematology, 030230 surgery, Article, 03 medical and health sciences, 0302 clinical medicine, Celiac artery, medicine.artery, parasitic diseases, medicine, business.industry, Median arcuate ligament, medicine.disease, Trunk, Surgery, MAL, median arcuate ligament, Stenosis, medicine.anatomical_structure, Ligament, lipids (amino acids, peptides, and proteins), business
Abstract: Highlights • Median Arcuate ligament(MAL) syndrome is rare disease. • MAL causes compression and stenosis of the celiac artery and lead symptoms. • 3-D CT angiography and doppler echogram is helpful for diagnosis. • Laparoscopic approach is effective and less invasive for patients. • Intraoperative doppler echogram is useful for confirmation of normal celiac arterial blood flow., Introduction MALS(Median Arcuate Ligament Syndrome) is rare disease. We experienced the case of MALS and successfully treated by laparoscopic approach. Presentation of case A 16-year-old male was admitted to our hospital with postprandial epigastric pain that had been present for 3 years. Abdominal three-dimensional computed tomographic angiography showed stenosis of the celiac trunk, and abdominal Doppler ultrasonography showed that the blood flow in the celiac trunk varied between inspiration and expiration. Hence, the patient was diagnosed with median arcuate ligament syndrome. Laparoscopic decompression of the celiac trunk was performed by division of the ligament and partial excision of the celiac plexus. Intraoperative Doppler ultrasonography showed markedly improved flow in the celiac artery. The patient was discharged from hospital on postoperative day 7, and has no recurrent symptoms at 12 months postoperatively. Discussion This case was most youngest male MALS treated by laparoscopic approach. Conclusion Laparoscopic division of the median arcuate ligament is a minimally invasive, safe, and effective method for decompression of the celiac artery.
Published: 2018

25. High secreted protein acidic and rich in cysteine expression in peritumoral fibroblasts predicts better prognosis in patients with resectable gastric cancer

Author: Nobuaki Suzuki, Yoshinobu Hoshii, Atsunori Oga, Ryoichi Tsunedomi, Noriko Maeda, Hiroaki Nagano, Shoichi Hazama, Shigeru Takeda, Hiroshi Itoh, Tomio Ueno, Shinsuke Kanekiyo, Masao Nakajima, Shigefumi Yoshino, Shigeru Yamamoto, and Kazuhiko Sakamoto
Subjects: 0301 basic medicine, Cancer Research, Pathology, medicine.medical_specialty, Stromal cell, Cell, Biology, 03 medical and health sciences, 0302 clinical medicine, medicine, stroma, Oncogene, gastric cancer, secreted protein acidic and rich in cysteine glycoprotein, Cancer, Articles, Cell cycle, medicine.disease, Molecular medicine, chemosensitivity, 030104 developmental biology, medicine.anatomical_structure, Oncology, Cancer cell, immunohistochemistry, Cancer research, Immunohistochemistry, 030211 gastroenterology & hepatology, prognosis
Abstract: Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix glycoprotein that may serve an important role in epithelial-mesenchymal transition. Recent studies have demonstrated that SPARC status is a prognostic indicator in various cancer types; however, its value remains unclear in gastric cancer (GC). In the present study, the localization and prognostic impact of SPARC expression were evaluated in patients with GC. Immunohistochemical analysis of SPARC expression was performed in 117 surgically resected GC specimens, and the localization of SPARC positive cells, as well as the rassociation between SPARC expression and clinicopathological characteristics were evaluated. High SPARC expression was observed in 47 cases; the glycoprotein was localized in the peritumoral fibroblasts, but was rarely observed in the cytoplasm of cancer cells. Heterogeneity of SPARC expression was observed in 52 cases. High stromal SPARC expression was identified to be an independent predictor of more favorable prognosis (overall survival and recurrence free survival) in all patients (P
Published: 2017

26. miR‐125b‐1 and miR‐378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer

Author: Ko Tahara, Hiroaki Tanaka, Shigeru Takeda, Michihisa Iida, Tomio Ueno, Yusuke Nakamura, Shigeru Yamamoto, Yoshitaro Shindo, Kazuhiko Sakamoto, Yoshihiro Tokuhisa, Yusuke Fujita, Hironori Tanaka, Hiroko Takenouchi, Nobuaki Suzuki, Yoshihiko Hamamoto, Shinobu Tomochika, Yukio Tokumitsu, Shigefumi Yoshino, Ryouichi Tsunedomi, Masao Nakajima, Hiroaki Nagano, Ryoichi Shimizu, Masahiko Kuroda, Shoichi Hazama, Koji Fujita, Kiyotaka Okuno, and Shinsuke Kanekiyo
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Stromal cell, Colorectal cancer, colorectal cancer, Laser Capture Microdissection, miR‐125b‐1, Bioinformatics, Cancer Vaccines, Mice, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Internal medicine, microRNA, Biomarkers, Tumor, peptide vaccine, Animals, Humans, Medicine, Laser capture microdissection, business.industry, miR‐378a, Cancer, Original Articles, Biomarker, General Medicine, Microarray Analysis, Prognosis, medicine.disease, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, 030220 oncology & carcinogenesis, Vaccines, Subunit, Cancer cell, Peptide vaccine, Biomarker (medicine), Female, Original Article, Colorectal Neoplasms, business
Abstract: Summary Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of this study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we performed microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were administered. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently we performed reverse transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells (P = 0.040), and miR-378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001). Multivariate analysis revealed that the expression of miR-378a in stromal cells showed the best performance among the 3 predictors (HR, 2.730; 95% CI, 1.027-7.585; P = 0.044). In conclusion, miR-125b-1 and miR-378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer. This article is protected by copyright. All rights reserved.
Published: 2017

27. Postoperative Adjuvant Therapy for Resectable Pancreatic Cancer With Gemcitabine and Adoptive Immunotherapy

Author: Shoichi Hazama, Hiroto Matsui, Shigefumi Yoshino, Shigeru Takeda, Nobuaki Suzuki, Yoshitaro Shindo, Kiyoshi Yoshimura, Tomio Ueno, Michihisa Iida, Kazuhiko Sakamoto, Masaaki Oka, Shinsuke Kanekiyo, Hiroaki Nagano, Satoshi Matsukuma, Masao Nakashima, and Yoshihiro Tokuhisa
Subjects: 0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Antimetabolites, Antineoplastic, Combination therapy, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, pancreatic cancer, MUC1, Kaplan-Meier Estimate, Deoxycytidine, Immunotherapy, Adoptive, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Pancreatic cancer, Internal Medicine, medicine, Adjuvant therapy, Humans, Postoperative Period, Aged, Aged, 80 and over, Hepatology, business.industry, Liver Neoplasms, Immunotherapy, Original Articles, Leukopenia, Middle Aged, medicine.disease, Combined Modality Therapy, Gemcitabine, Pancreatic Neoplasms, Regimen, 030104 developmental biology, 030220 oncology & carcinogenesis, Pancreatectomy, Multivariate Analysis, Female, Neoplasm Recurrence, Local, business, adoptive immunotherapy, medicine.drug
Abstract: Objectives We previously described adoptive immunotherapy (AIT) with cytotoxic T lymphocytes (CTLs) stimulated by the mucin 1 (MUC1)-expressing human pancreatic cancer cell line YPK-1 (MUC1-CTLs) and demonstrated that MUC1-CTLs might prevent liver metastasis. In the present study, we combined gemcitabine (GEM) and AIT for the treatment of pancreatic cancer. Methods A total of 43 patients who underwent radical pancreatectomy received treatment with MUC1-CTLs and GEM. After surgery, MUC1-CTLs were induced and administered intravenously 3 times, and GEM administered according to the standard regimen for 6 months. The patients whose relative dose intensity of GEM was 50% or more and who received 2 or more MUC1-CTL treatments were used as the adequate treatment group (n = 21). Results In the adequate treatment group, disease-free survival was 15.8 months, and overall survival was 24.7 months. Liver metastasis was found only in 7 patients (33%), and local recurrence occurred in 4 patients (19%). The independent prognostic factor of long-term disease-free survival on multivariate analysis was the average number of CTLs administered (P = 0.0133). Conclusions The combination therapy with AIT and GEM prevented liver metastasis and local recurrence. Moreover, the disease free-survival was improved in patients who received sufficient CTLs.
Published: 2017

28. Cetuximab strongly enhances immune cell infiltration into liver metastatic sites in colorectal cancer

Author: Shigeru Takeda, Ryouichi Tsunedomi, Hiroaki Nagano, Nobuaki Suzuki, Tomio Ueno, Yuka Inoue, Yukio Tokumitsu, Yoshihiro Tokuhisa, Shigefumi Yoshino, Shinsuke Kanekiyo, Michihisa Iida, Shoichi Hazama, Shinobu Tomochika, and Kazuhiko Sakamoto
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, CD3 Complex, Organoplatinum Compounds, Oxaloacetates, Colorectal cancer, medicine.medical_treatment, Leucovorin, Cetuximab, Deoxycytidine, Metastasis, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Aged, 80 and over, immune‐enhancing effect, Liver Neoplasms, General Medicine, Middle Aged, CD56 Antigen, Bevacizumab, 030220 oncology & carcinogenesis, Immunogenic cell death, Original Article, Female, Fluorouracil, Colorectal Neoplasms, medicine.drug, Adult, medicine.medical_specialty, CD8 Antigens, colorectal cancer, Antineoplastic Agents, Irinotecan, 03 medical and health sciences, Antibody‐dependent cellular cytotoxicity, Clinical Research, Internal medicine, medicine, Humans, TILs, neoplasms, Capecitabine, Aged, Inflammation, Tumor microenvironment, Chemotherapy, business.industry, Original Articles, Immunotherapy, medicine.disease, digestive system diseases, 030104 developmental biology, Cancer cell, Camptothecin, business
Abstract: Summary Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy. The inflammatory cells in the liver metastatic sites were assessed by hematoxylin-eosin staining, focusing on the invasive margin. The overall inflammatory reaction and number of lymphoid cells were assessed with a four-point scoring system. We then assessed immune cell infiltration (CD3, CD8 and CD56) in 15 liver metastatic sites. Hematoxylin-eosin staining demonstrated more inflammatory cells in the chemotherapy with cetuximab group than in the other groups (p < 0.001). Of note, inflammatory cells were found in intratumoral areas, and the destruction of cancer cell foci was observed in the chemotherapy with cetuximab group. Moreover, a higher infiltration of CD3+ (p = 0.003), CD8+ (p = 0.003) and CD56+ (p = 0.001) cells was observed in the chemotherapy with cetuximab group than in the other groups. These results suggest that cetuximab might have an immune-enhancing effect. As such, the immune-related mechanism of action of cetuximab may enhance the efficacy of combination therapy, such as chemotherapy and immunotherapy using therapeutic peptides. This article is protected by copyright. All rights reserved.
Published: 2017

29. Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS-PC study

Author: Hiroaki Tanaka, Hiroto Hayashi, Haruo Iguchi, Nobuaki Suzuki, Yasunobu Koki, Tomio Ueno, Yusuke Nakamura, Tetsuya Ikemoto, Hideki Arima, Hiroyuki Furukawa, Kosei Hirakawa, Hiroaki Nagano, Masaaki Oka, Yoshitaro Shindo, Hiroto Matsui, Hiroko Takenouchi, Ryoichi Shimizu, Kazuhiro Uesugi, Kazuhiko Yoshimatsu, Toshiyoshi Fujiwara, Hidenobu Ishizaki, Michihisa Iida, Shoichi Hazama, Koichiro Sakata, Yuzo Umeda, Shigefumi Yoshino, Takashi Hatori, Mitsuo Shimada, and Atsushi Aruga
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, Time Factors, HLA-A24 Antigen, Kinesins, Deoxycytidine, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Advanced pancreatic cancer, Aged, 80 and over, General Medicine, phase II, Middle Aged, Prognosis, Treatment Outcome, 030220 oncology & carcinogenesis, Original Article, Female, immunotherapy, medicine.drug, Adult, medicine.medical_specialty, Cancer Vaccines, Disease-Free Survival, 03 medical and health sciences, Clinical Research, Internal medicine, Pancreatic cancer, Injection site reaction, peptide cocktail, medicine, Humans, Progression-free survival, Survival rate, Aged, Vascular Endothelial Growth Factor Receptor-1, business.industry, Cancer, Original Articles, medicine.disease, Vascular Endothelial Growth Factor Receptor-2, Gemcitabine, Pancreatic Neoplasms, Clinical trial, 030104 developmental biology, CTL, Immunology, Peptide vaccine, Peptides, business, T-Lymphocytes, Cytotoxic
Abstract: We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1-year survival rate, and secondarily overall survival (OS), progression free survival (PFS), response rate (RR), disease control rate (DCR) and the peptide-specific immune responses. All enrolled patients received therapy without the HLA-A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1-year survival rates between the HLA-A*2402-matched and -unmatched groups were not significantly different. In the HLA-A*2402 matched group, patients showing peptide-specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (P = 0.023, P = 0.009, respectively). In the HLA-A*2402-matched group, the patients who showed a strong injection site reaction had a better survival rate (P = 0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide-specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application.
Published: 2016

30. Prediction of the efficacy of immunotherapy by measuring the integrity of cell‐free <scp>DNA</scp> in plasma in colorectal cancer

Author: Shoichi Hazama, Kazuhiko Sakamoto, Yuka Inoue, Shigeru Takeda, Shinsuke Kanekiyo, Shigeru Yamamoto, Ryouichi Tsunedomi, Masao Nakajima, Shigefumi Yoshino, Tomio Ueno, Michihisa Iida, Yoshihiro Tokuhisa, Hiroko Takenouchi, Masahiro Kitahara, Shinobu Tomochika, Hiroaki Nagano, and Nobuaki Suzuki
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Phases of clinical research, colorectal cancer, Kaplan-Meier Estimate, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Internal medicine, Biomarkers, Tumor, medicine, Humans, Neoplasm Metastasis, cell‐free DNA, Aged, Neoplasm Staging, Proportional Hazards Models, Chemotherapy, business.industry, Original Articles, Biomarker, DNA, Neoplasm, General Medicine, Immunotherapy, Middle Aged, Prognosis, medicine.disease, Treatment Outcome, 030104 developmental biology, Cell-free fetal DNA, 030220 oncology & carcinogenesis, Cancer cell, DNA integrity, Biomarker (medicine), Original Article, Female, Cancer vaccine, Colorectal Neoplasms, business
Abstract: We previously reported a phase II study of a cancer vaccine using five novel peptides recognized by HLA-A*2402-restricted CTL in combination with oxaliplatin-containing chemotherapy (FXV study) as first-line therapy for patients with metastatic colorectal cancer and demonstrated the safety and promising potential of our five-peptide cocktail. The objective of this analysis was to identify predictive biomarkers for identifying patients who are likely to receive a clinical benefit from immunochemotherapy. Circulating cell-free DNA (cfDNA) in plasma has been reported to be a candidate molecular biomarker for the efficacy of anticancer therapy. Unlike uniformly truncated small-sized DNA released from apoptotic normal cells, DNA released from necrotic cancer cells varies in size. The integrity of plasma cfDNA (i.e. the ratio of longer fragments [400 bp] to shorter fragments [100 bp] of cfDNA), may be clinically useful for detecting colorectal cancer progression. We assessed plasma samples collected from 93 patients prior to receiving immunochemotherapy. The cfDNA levels and integrity were analyzed by semi-quantitative real-time PCR. Progression-free survival was significantly better in patients with a low plasma cfDNA integrity value than in those with a high value (P = 0.0027). Surprisingly, in the HLA-A*2402-matched group, patients with a low plasma cfDNA integrity value had significantly better progression-free survival than those with a high value (P = 0.0015). This difference was not observed in the HLA-A*2402-unmatched group. In conclusion, the integrity of plasma cfDNA may provide important clinical information and may be a useful predictive biomarker of the outcome of immunotherapy in metastatic colorectal cancer.
Published: 2016

31. Calreticulin is highly expressed in pancreatic cancer stem‐like cells

Author: Reo Kawano, Hidetoshi Eguchi, Hiroshi Itoh, Shigefumi Yoshino, Kiyoshi Yoshimura, Hiroaki Nagano, Yusaku Watanabe, Tomoko Furuya-Kondo, Masaaki Oka, Hiroto Matsui, Noriko Maeda, Satoshi Nagaoka, Ryouichi Tsunedomi, Tomio Ueno, Atsuo Kuramasu, Shoichi Hazama, Atsunori Oga, Masanori Fuse, Yoshitaro Shindo, Yoshihiro Tokuhisa, Moeko Inoue, and Satoshi Matsukuma
Subjects: cancer stem cells, Proteomics, 0301 basic medicine, Cancer Research, Pathology, medicine.medical_specialty, pancreatic cancer, Population, CD47 Antigen, Kaplan-Meier Estimate, Biology, Metastasis, calreticulin, 03 medical and health sciences, 0302 clinical medicine, Cell, Molecular, and Stem Cell Biology, Side population, Cancer stem cell, Cell Line, Tumor, Pancreatic cancer, medicine, Humans, education, Proportional Hazards Models, education.field_of_study, Cancer, Original Articles, General Medicine, Prognosis, medicine.disease, Pancreatic Neoplasms, Hyaluronan Receptors, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Cancer research, Biomarker (medicine), Original Article, ATP-Binding Cassette Transporters, CA19-9, Biomarkers
Abstract: Cancer stem-like cells (CSLCs) in solid tumors are thought to be resistant to conventional chemotherapy or molecular targeting therapy and to contribute to cancer recurrence and metastasis. In this study, we aimed to identify a biomarker of pancreatic CSLCs (P-CSLCs). A P-CSLC-enriched population was generated from pancreatic cancer cell lines using our previously reported method and its protein expression profile was compared with that of parental cells by 2-D electrophoresis and tandem mass spectrometry. The results indicated that a chaperone protein calreticulin (CRT) was significantly upregulated in P-CSLCs compared to parental cells. Flow cytometry analysis indicated that CRT was mostly localized to the surface of P-CSLCs and did not correlate with the levels of CD44v9, another P-CSLC biomarker. Furthermore, the side population in the CRThigh /CD44v9low population was much higher than that in the CRTlow /CD44v9high population. Calreticulin expression was also assessed by immunohistochemistry in pancreatic cancer tissues (n = 80) obtained after radical resection and was found to be associated with patients' clinicopathological features and disease outcomes in the Cox proportional hazard regression model. Multivariate analysis identified CRT as an independent prognostic factor for pancreatic cancer patients, along with age and postoperative therapy. Our results suggest that CRT can serve as a biomarker of P-CSLCs and a prognostic factor associated with poorer survival of pancreatic cancer patients. This novel biomarker can be considered as a therapeutic target for cancer immunotherapy.
Published: 2016

32. Identification of a Promiscuous Epitope Peptide Derived From HSP70

Author: Tomio Ueno, Shigeru Takeda, Yasuharu Nishimura, Shoichi Hazama, Shinobu Tomochika, Atsushi Irie, Tomoya Miyakawa, Yukio Tokumitsu, Masao Nakajima, Hiroaki Nagano, Shigeru Yamamoto, Shin Yoshida, Shun Doi, Nobuaki Suzuki, Shinsuke Kanekiyo, Koji Tamada, Hiroto Matsui, Yoshitaro Shindo, Keiko Udaka, Michihisa Iida, and Shigefumi Yoshino
Subjects: 0301 basic medicine, Cancer Research, tumor-associated antigen, Immunology, Peptide binding, Peptide, Basic Studies, heat-shock protein 70, CD8-Positive T-Lymphocytes, Major histocompatibility complex, Cancer Vaccines, Epitope, 03 medical and health sciences, Epitopes, Interferon-gamma, Mice, 0302 clinical medicine, Antigen, Antigens, Neoplasm, Immunology and Allergy, Animals, Humans, HSP70 Heat-Shock Proteins, Amino Acid Sequence, Peptide sequence, Pharmacology, chemistry.chemical_classification, biology, HLA-A Antigens, Chemistry, ELISPOT, Dendritic Cells, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Peptide vaccine, Cancer research, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, immunotherapy, Peptides, epitope peptide, cancer vaccine, T-Lymphocytes, Cytotoxic
Abstract: Supplemental Digital Content is available in the text., We previously found that heat-shock protein 70 (HSP70) is expressed on hepatocellular carcinoma cells and developed an HSP70 mRNA-transfected dendritic cell therapy for treating unresectable or recurrent hepatocellular carcinoma. The phase I trial was completed successfully. The purpose of this study is to identify a promiscuous epitope peptide derived from HSP70 for the purpose of developing a novel cancer peptide vaccine. Using a computational algorithm to analyze the specificity of previously reported major histocompatibility complex class I–binding peptides, we selected candidates that bound to >2 of the 3 HLA types. Twenty-nine HSP70-derived peptides (9-mers) that bound to HLA-class I was selected. The peptides were prioritized based on the results of peptide binding experiments. Using dendritic cells stimulated with the candidate peptide described previously as stimulators and CD8+ T cells as effectors, an ELISPOT assay was performed. Cytotoxicity of CD8 lymphocytes stimulated with the candidate peptides toward HSP70-expressing cancer cells was analyzed using an xCELLigence System. Peptides were administered to HLA-A 24 transgenic mice as vaccines, and peptide-specific T-cell induction was measured in vivo. We identified a multi-HLA-class I–binding epitope peptide that bound to HLA-A*02:01, *02:06, and *24:02 in vitro using an interferon-γ ELISPOT immune response induction assay. Cytotoxicity was confirmed in vitro, and safety and immune response induction were confirmed in vivo using HLA-A 24 transgenic mice. Our study demonstrated that the promiscuous HSP70-derived peptide is applicable to cancer immunotherapy in patients with HLA-A*24:02-positive, *02:01-positive, and *02:06-positive HSP70-expressing cancers.
Published: 2019

33. Clinical significance of preoperative chemoradiotherapy for advanced esophageal cancer, evaluated by propensity score matching and weighting of inverse probability of treatment

Author: Masanori Tsujie, Kotaro Kitani, Yoshinori Fujiwara, Hisako Kubota, Atsushi Tsuruta, Masao Yukawa, Masaharu Higashida, Yusaku Watanabe, Masatoshi Inoue, Shuichi Fukuda, Tomio Ueno, and Toshimasa Okada
Subjects: Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, chemoradiotherapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, esophageal cancer, propensity score, Univariate analysis, business.industry, Hazard ratio, Articles, Esophageal cancer, medicine.disease, Primary tumor, Confidence interval, Esophagectomy, 030220 oncology & carcinogenesis, Propensity score matching, esophagectomy, 030211 gastroenterology & hepatology, business, Chemoradiotherapy
Abstract: The present study used inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to compare survival benefits among 112 patients with resectable, stage II–IV esophageal squamous cell carcinoma (SCC) treated between 1996 and 2016 with neoadjuvant chemoradiotherapy (NAC) plus surgery (Group A, n=55) or with surgery alone (Group B, n=57). Their propensity scores (PS) were calculated using a multivariable logistic regression model in which age, sex, cancer site, primary tumor length, cTNM stage, lymph node metastasis and depth of tumor invasion were the independent variables, and used to match Groups A and B according to the IPTW and matching method. After IPTW and PSM, univariate analysis was used to assess overall survival (OS) and disease-free survival (DFS), followed by Cox proportional hazard models for OS using IPTW between the two groups and the subgroups. After PSM, 5-year OS and DFS were significantly higher in Group A (OS: 65.2%, DFS: 65.2%) compared with Group B (OS: 31.2%, DFS: 20.87%). Similarly, after IPTW, OS and DFS were significantly higher in Group A compared with Group B patients. Five-year OS was 73.18% for Group A and 37.69% for Group B (hazard ratio: 0.2899, 95% confidence interval: 0.1167–0.7205). To conclude, treatment was more effective in Group A patients with clinical stage II, N0 and T3 disease involving the mid-esophagus. It was concluded that for patients with esophageal SCC, NAC plus esophagectomy exhibited improved survival compared with surgery alone, as demonstrated by use of IPTW and PSM methods.
Published: 2019

34. Utility of scoring systems combining the product of tumor number and size with liver function for predicting the prognosis of patients with hepatocellular carcinoma after hepatectomy

Author: Hiroto Matsui, Shogo Kobayashi, Masao Nakajima, Shigeru Takeda, Hiroaki Nagano, Hidetoshi Eguchi, Yoshitaro Shindo, Nobuaki Suzuki, Hiroshi Wada, Yukio Tokumitsu, Satoshi Matsukuma, and Tomio Ueno
Subjects: 0301 basic medicine, Cancer Research, Univariate analysis, medicine.medical_specialty, business.industry, Proportional hazards model, medicine.medical_treatment, Hazard ratio, Cancer, Articles, medicine.disease, Gastroenterology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Hepatocellular carcinoma, Medicine, Liver function, Hepatectomy, business, Liver cancer
Abstract: Our previous study reported the effectiveness of the product of tumor number and size (NxS factor) as a predictor of the prognosis of patients with hepatocellular carcinoma (HCC) following hepatectomy. The aim of the present study was to validate the prognostic value of scoring systems based on the NxS factor for HCC. The records of 940 patients who underwent hepatectomy for HCC at Osaka University Graduate School of Medicine and Osaka International Cancer Institute were analyzed. The discriminatory abilities of the mathematical integrated model for tumor staging (MITS) score, which combines the NxS factor with liver function, and known prognostic systems, including the Japan Integrated Staging system, the Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program and the Tokyo system, were compared. Firstly, the present study demonstrated that a higher NxS factor was associated with decreased disease-free survival (DFS) and overall survival (OS) in patients with HCC (P
Published: 2019

35. Correction to: Novel adjuvant dendritic cell therapy with transfection of heat-shock protein 70 messenger RNA for patients with hepatocellular carcinoma: a phase I/II prospective randomized controlled clinical trial

Author: Hiroto Matsui, Shoichi Hazama, Masao Nakajima, Ming Xu, Satoshi Matsukuma, Yukio Tokumitsu, Yoshitaro Shindo, Shinobu Tomochika, Shin Yoshida, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, Shigefumi Yoshino, Tomio Ueno, Masaaki Oka, and Hiroaki Nagano
Subjects: Cancer Research, Oncology, Immunology, Immunology and Allergy
Published: 2021

36. Outcomes following liver resection for multinodular Barcelona Clinic Liver Cancer‑B hepatocellular carcinoma

Author: Hidetoshi Eguchi, Nobuaki Suzuki, Shogo Kobayashi, Hiroshi Wada, Michihisa Iida, Hiroaki Nagano, Yoshihiro Tokuhisa, Kazuhiko Sakamoto, Issei Saeki, Tomio Ueno, Isao Sakaida, Satoshi Matsukuma, Masato Sakon, Shinsuke Kanekiyo, Shinobu Tomochika, Yukio Tokumitsu, Shigeru Takeda, and Hiroto Matsui
Subjects: Cancer Research, medicine.medical_specialty, Multivariate analysis, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Stage (cooking), intermediate stage, Oncogene, business.industry, Cancer, Articles, hepatocellular carcinoma, medicine.disease, Molecular medicine, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, liver resection, Cohort, 030211 gastroenterology & hepatology, Liver cancer, business, Barcelona Clinic Liver Cancer classification
Abstract: Management of multinodular hepatocellular carcinoma (HCC) in the intermediate Barcelona Clinic Liver Cancer (BCLC)-B stage is controversial. The aim of the present study as to identify the subgroup of patients with BCLC-B HCC who could benefit from liver resection. The present study retrospectively analyzed the outcomes of 65 patients (training cohort) who underwent liver resection for multinodular BCLC-B HCC. Cox's regression analysis was conducted to identify the independent prognostic factors for overall survival and to develop the prognostic score. As some authors have reported that maximum tumor size (cm) plus tumor number (N+S) is a prognostic factor in patients with BCLC-B HCC who undergo chemoembolization, the usefulness of this factor in patients who underwent liver resection was also evaluated. Subsequently, the validity of the prognostic score was assessed in an independent validation cohort (n=132). Multivariate analysis revealed that positivity for hepatitis C virus antibody (HCV-ab), platelet count ≤1010/l, N+S >8, and des-γ-carboxy prothrombin (DCP) >400 mAU/ml were independent prognostic factors for overall survival. The prognostic score differentiated two groups (≤2, ≥3) with distinct outcomes (median survival time 68.3 months vs. 29.1 months; P
Published: 2018

37. Overexpression of miR‑221 and miR‑222 in the cancer stroma is associated with malignant potential in colorectal cancer

Author: Michihisa Iida, Ryouichi Tsunedomi, Kazuhiko Sakamoto, Nobuaki Suzuki, Yukio Tokumitsu, Shinobu Tomochika, Koji Fujita, Shigeru Takeda, Tomio Ueno, Yoshihiro Tokuhisa, Hiroaki Nagano, Masahiko Kuroda, Shigefumi Yoshino, Shinsuke Kanekiyo, Shoichi Hazama, Hiroko Takenouchi, Shigeru Yamamoto, and Hironori Tanaka
Subjects: 0301 basic medicine, Male, Cancer Research, Colorectal cancer, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Stroma, microRNA, Biomarkers, Tumor, Medicine, Humans, Aged, Aged, 80 and over, Oncogene, business.industry, Gene Expression Profiling, Liver Neoplasms, Cancer, General Medicine, Middle Aged, medicine.disease, Prognosis, Molecular medicine, Gene Expression Regulation, Neoplastic, Survival Rate, MicroRNAs, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Case-Control Studies, Lymphatic Metastasis, Cancer cell, Cancer research, Female, Stromal Cells, business, Colorectal Neoplasms, Follow-Up Studies
Abstract: The cancer stroma is important in cancer development, however, whether the aberrant expression of microRNAs (miRNAs) in the cancer stroma is associated with cancer progression remains to be fully elucidated. The aim of the present study was to identify the miRNAs associated with liver metastasis in the cancer stroma of human colorectal cancer (CRC). Using laser capture microdissection, cancer stroma was obtained from the primary lesion of six patients with CRC with liver metastasis (CRCwLM) and six patients with CRC without liver metastasis (CRCwoLM), and miRNA microarray analysis was performed. Candidate miRNA expression status in the stroma was validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis in 40 CRC cases (wLM, n=20; woLM, n=20), and the association between miRNA expression and clinicopathological factors was assessed in 101 advanced CRC samples. The localization of candidate miRNAs in CRCs was analyzed using in situ hybridization analysis (ISH). The microarray analysis identified six miRNAs with expression differing between the CRCwLM and CRCwoLM cancer stroma. Validation using RT‑qPCR analysis of the stroma showed that the expression levels of miR‑221 and miR‑222 in the cancer stroma were significantly higher in CRCwLM than in CRCwoLM. The RT‑qPCR analysis of 101 CRC samples showed that a high expression level of miR‑221 or miR‑222 in the cancer stroma was associated with liver metastasis, distant metastasis, and shorter overall survival rate of patients with CRC (P
Published: 2018

38. A new prognostic model for hepatocellular carcinoma recurrence after curative hepatectomy

Author: Hiroyuki Ogihara, Hiroshi Wada, Yukio Tokumitsu, Norio Iizuka, Yusuke Fujita, Yoshinari Maeda, Tomio Ueno, Yoshihiro Tokuhisa, Hiroto Matsui, Yoshihiko Hamamoto, Kazuhiko Sakamoto, Koichiro Sakata, Hiroaki Nagano, Hidetoshi Eguchi, and Satoshi Matsukuma
Subjects: Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Vein, Survival analysis, Receiver operating characteristic, business.industry, Area under the curve, Cancer, Articles, medicine.disease, medicine.anatomical_structure, Oncology, chemistry, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Hepatectomy, business, Indocyanine green
Abstract: We previously reported the effectiveness of the product of tumor number and size (NxS factor) for the prognosis of hepatocellular carcinoma (HCC) in patients following hepatectomy. The present study aimed to propose a new score based on the NxS factor to predict HCC recurrence following hepatectomy. A total of 406 patients who underwent hepatectomy for HCC at Osaka University Graduate School of Medicine were retrospectively analyzed to develop the new score. Among clinicopathological factors, including the NxS factor, the marker subset that achieved the best performance for prediction of early recurrence was assessed, and a prognostic model for HCC recurrence after curative hepatectomy (REACH) was developed. As the validation set, 425 patients who underwent hepatectomy for HCC at Yamaguchi University Graduate School of Medicine and Shimonoseki Medical Center were analyzed, and the prognostic ability of the REACH score was compared with that of well-known staging systems. Following analysis, the REACH score was constructed using six covariates (NxS factor, microscopic hepatic vein invasion, differentiation, serum albumin, platelet count and indocyanine green retention rate at 15 min). In the validation set, the REACH score predicted early recurrence in 73 of 81 samples, with a sensitivity of 89% and a specificity of 58%. The area under the curve (AUC) of the receiver operating characteristic curve of the REACH score was 0.78 and 0.74, respectively, for 1- and 2-year recurrence after hepatectomy; each AUC was higher than that of any of the other staging systems. Survival analysis indicated the REACH score had the best predictive value in disease-free and overall survival. The present findings demonstrated that the REACH score may be used to classify patients with HCC into high- and low-risk of recurrence, and to predict subsequent survival following hepatic resection.
Published: 2018

39. Perioperative Predictive Markers for Recurrence of Esophageal Cancer after Esophagectomy.

Author: Yoshinori Fujiwara, Masaharu Higashida, Hisako Kubota, Yuko Okamoto, Shumei Mineta, Shunji Endo, and Tomio Ueno
Subjects: ESOPHAGEAL cancer, ESOPHAGECTOMY, C-reactive protein, BODY mass index, CANCER invasiveness
Abstract: Introduction: We studied whether perioperative nutritional, immunological factors or postoperative inflammatory responses predicted esophageal cancer (EC) progression and prognosis in patients who received esophagectomies. Methods: We evaluated preoperative prognostic nutritional index (PNI), BMI, neutrophil-to-lymphocyte ratio (NLR), intraoperative blood loss, postoperative C-reactive protein (CRP) max, recurrence-free survival (RFS), and overall survival (OS) in 111 patients with pStage I-IV squamous cell EC who received esophagectomies. Optimal cutoff values for each continuous parameter were determined by receiver operating characteristic curves and Youden indices. Univariate and multivariate Cox analyses were used to derive independent prognostic factors. Propensity score matching using inverse probability of treatment weighting was used in groups divided by Youden indices, as appropriate. Results: Cutoff values of continuous variables were NLR: 2.27, PNI: 44.2, blood loss: 159 mL, and CRPmax: 21.7 mg/dL. In multivariate analyses, PNI, CRPmax, and intraoperative blood loss were independent prognostic factors for OS and RFS. Among patients with stage II-IV disease, low PNI was associated with shorter RFS. Postoperative respiratory complications were associated with both higher CRP and shorter RFS. Discussion/Conclusions: Low preoperative PNI and high postoperative inflammatory response were associated with postoperative EC progression after esophagectomy. Preoperative nutritional interventions or suppression of postoperative inflammatory response, including respiratory complications, may improve patient prognosis. [ABSTRACT FROM AUTHOR]
Published: 2021
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40. An accurate prognostic staging system for hepatocellular carcinoma patients after curative hepatectomy

Author: Hiroyuki Ogihara, Yusuke Fujita, Masaaki Oka, Norio Iizuka, Yoshihiko Hamamoto, Takao Tamesa, Tomio Ueno, Yoshihiro Tokuhisa, Satoshi Matsukuma, Yukio Tokumitsu, Yoshinari Maeda, Shoichi Hazama, Noriaki Hashimoto, and Kazuhiko Sakamoto
Subjects: Akaike information criterion, Male, Oncology, Cancer Research, medicine.medical_specialty, recurrence, Carcinoma, Hepatocellular, medicine.medical_treatment, Disease-Free Survival, Internal medicine, staging system, medicine, Hepatectomy, Humans, Mathematical Product, prognostic factor, Survival rate, Staging system, Neoplasm Staging, business.industry, Liver Neoplasms, Significant difference, Cancer, Articles, hepatocellular carcinoma, Middle Aged, Prognosis, medicine.disease, Survival Rate, Hepatocellular carcinoma, Female, Liver function, Neoplasm Recurrence, Local, business
Abstract: The aim of this study was to develop an accurate predictive system for prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy. We pooled data of clinicopathological features of 234 HCC patients who underwent curative hepatectomy. On the basis of the pooled data, we established a simple predictive staging system (PS score) scored by the mathematical product of tumor number and size, and degree of liver function. We compared the prognostic abilities of the PS score (score 0–3) with those of six well-known clinical staging systems. Then, we found that there were significant differences (P
Published: 2014

41. Metastatic ability and the epithelial-mesenchymal transition in induced cancer stem-like hepatoma cells

Author: Kazuhiko Sakamoto, Nobuaki Suzuki, Hiroyuki Ogihara, Mitsuo Nishiyama, Yoshihiko Hamamoto, Kiyoshi Yoshimura, Tomio Ueno, Michihisa Iida, Shinsuke Kanekiyo, Noriaki Hashimoto, Ryouichi Tsunedomi, Shigeru Yamamoto, Shigeru Takeda, Hiroaki Nagano, Shoichi Hazama, Shigefumi Yoshino, and Satoshi Matsukuma
Subjects: 0301 basic medicine, Cancer Research, cancer stem cell, Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, Vimentin, intrahepatic metastasis, Biology, Metastasis, 03 medical and health sciences, Mice, 0302 clinical medicine, Cell, Molecular, and Stem Cell Biology, Cancer stem cell, Cell Line, Tumor, medicine, Animals, Humans, Epithelial–mesenchymal transition, Neoplasm Metastasis, Mesenchymal stem cell, CD44, Liver Neoplasms, EMT, Cancer, General Medicine, Original Articles, hepatoma, medicine.disease, Up-Regulation, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Hyaluronan Receptors, CD44v, Oncology, Cell culture, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Neoplastic Stem Cells, Original Article, Transcription Factors
Abstract: Cancer stem cells (CSCs) are thought to play important roles in cancer malignancy. Previously, we successfully induced sphere cancer stem-like cells (CSLCs) from several cell lines and observed the property of chemoresistance. In the present study, we examined the metastatic potential of these induced CSLCs. Sphere cancer stem-like cells were induced from a human hepatoma cell line (SK-HEP-1) in a unique medium containing neural survival factor-1. Splenic injection of cells into immune-deficient mice was used to assess hematogenous liver metastasis. Transcriptomic strand-specific RNA-sequencing analysis, quantitative real-time PCR, and flow cytometry were carried out to examine the expression of epithelial-mesenchymal transition (EMT)-related genes. Splenic injection of CSLCs resulted in a significantly increased frequency of liver metastasis compared to parental cancer cells (P
Published: 2017

42. Correlation Between NKG2DL Expression and Antitumor Effect of Protein-bound Polysaccharide-K in Tumor-bearing Mouse Models

Author: Tomio Ueno, Shigeru Yamamoto, Mariko Kato, Kazunori Aoki, Motoyuki Uchida, Masaaki Oka, Shigeru Takeda, Masanori Fuse, Moeko Inoue, Tsutomu Wada, Fujioka Masaki, Ryoji Kamei, Tetsuhiko Asao, Satoshi Wada, Hiroko Iijima, Kiyoshi Yoshimura, Noboru Yamamoto, Shigefumi Yoshino, Atsuo Kuramasu, Ayano Konagai, Shouichi Hazama, and Hiroaki Nagano
Subjects: 0301 basic medicine, Cancer Research, Nucleocytoplasmic Transport Proteins, Tumor immunity, CD8-Positive T-Lymphocytes, Polysaccharide, Ligands, Fungal Proteins, Minor Histocompatibility Antigens, 03 medical and health sciences, Mice, 0302 clinical medicine, Nuclear Matrix-Associated Proteins, Polysaccharides, Cell Line, Tumor, Neoplasms, Animals, Humans, Tumor growth, chemistry.chemical_classification, General Medicine, NKG2D, Xenograft Model Antitumor Assays, Protein bound polysaccharide, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, chemistry, Cell culture, NK Cell Lectin-Like Receptor Subfamily K, 030220 oncology & carcinogenesis, Immuno therapy, Cancer research, CD8
Abstract: Background/aim We investigated the relationship between the expression of natural killer group 2, member D ligands (NKG2DLs) and the antitumor effects of protein-bound polysaccharide-K (PSK). Materials and methods PSK was administered to evaluate its effectiveness against tumor growth. The expression of Rae-1 and H60 were analyzed in multiple cell lines. Results PSK showed the highest antitumor effects in mice implanted with cells expressing neither Rae-1 nor H60. PSK had little antitumor effect in mice implanted with cells expressing both Rae-1 and H60. A correlation between the expression of NKG2DLs and the antitumor effect of PSK was observed. After PSK administration, INF-γ production in CD8+ T cells increased in mice with cells expressing neither Rae-1 nor H60, but did not change in mice implanted with cells expressing both Rae-1 and H60. Conclusion We demonstrated that the expression of NKG2DLs affects tumor immunity and the efficacy of immuno therapy in tumor-bearing mouse model.
Published: 2017

43. Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase II study on advanced pancreatic cancer

Author: Masaaki Oka, Michihisa Iida, Hiroko Takenouchi, Hideki Arima, Yusuke Nakamura, Tetsuya Ikemoto, Atsushi Aruga, Yutaka Kawakami, Kazuhiko Yoshimatsu, Hiroyuki Furukawa, Hidenobu Ishizaki, Toshiyoshi Fujiwara, Nobuaki Suzuki, Hiroto Matsui, Shinsuke Kanekiyo, Haruo Iguchi, Mitsuo Shimada, Tomio Ueno, Yoshitaro Shindo, Shoichi Hazama, Hiroaki Tanaka, Yuzo Umeda, Shigefumi Yoshino, Kazuhiro Uesugi, Takashi Hatori, Yasunobu Koki, Hiroaki Nagano, and Tomonobu Fujita
Subjects: CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, T cell, Programmed Cell Death 1 Receptor, HLA-A24 Antigen, Tim-3, Human leukocyte antigen, CD8-Positive T-Lymphocytes, Cancer Vaccines, 03 medical and health sciences, 0302 clinical medicine, Pancreatic cancer, Internal medicine, PD-1, Biomarkers, Tumor, Humans, Medicine, Cytotoxic T cell, Hepatitis A Virus Cellular Receptor 2, Aged, Peptide vaccine, biology, business.industry, Research, Middle Aged, medicine.disease, Up-Regulation, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, Predictive biomarker, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Vaccines, Subunit, biology.protein, Female, Cancer vaccine, Antibody, business, CD8
Abstract: Background The purpose of the present study was to explore novel biomarkers that can predict the clinical outcome of patients before treatment or during vaccination. These would be useful for the selection of appropriate patients who would be expected to exhibit better treatment outcomes from vaccination, and for facilitating the development of cancer vaccine treatments. Methods From a single-arm, non-randomized, human leukocyte antigen (HLA)-A-status-blind phase II trial of a vaccine treatment using three HLA-A*2402-restricted peptides for advanced pancreatic cancer (PC), we obtained peripheral blood samples from 36 patients of an HLA-A*2402-matched group and 27 patients of an HLA-A*2402-unmatched group. Results Multivariate analysis (HR = 2.546; 95% CI = 1.138 to 5.765; p = 0.0231) and log-rank test (p = 0.0036) showed that a high expression level of programmed death-1 (PD-1) on CD4+ T cells was a negative predictive biomarker of overall survival in the HLA-A*2402-matched group . Moreover, a high expression level of PD-1 on CD4+ T cells was a negative predictor for the induction of cytotoxic T lymphocytes (p = 0.0007). After treatment, we found that the upregulation of PD-1 and T cell immunoglobulin mucin-3 (Tim-3) expression on CD4+ and CD8+ T cells was significantly associated with a poor clinical outcome in the HLA-A*2402-matched group (p = 0.0330, 0.0282, 0.0046, and 0.0068, respectively). In contrast, there was no significant difference for these factors in the HLA-A*2402-unmatched group. Conclusions Our results indicate that the upregulation of PD-1 and Tim-3 expression on CD4+ and CD8+ T cells may restrict T cell responses in advanced PC patients; therefore, combination immunotherapy with blockade of PD-1 and Tim-3 to restore T cell responses may be a potential therapeutic approach for advanced PC patients. Trial registration Clinical-Trail-Registration: UMIN000008082. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0509-1) contains supplementary material, which is available to authorized users.
Published: 2017

44. Association of tumor necrosis factor-α polymorphism with chemotherapy-induced oral mucositis in patients with esophageal cancer

Author: Naoko Okayama, Kazuhiko Sakamoto, Shigeru Yamamoto, Mitsuo Nishiyama, Tomio Ueno, Shigefumi Yoshino, Shigeru Takeda, Masahiro Kitahara, Shinsuke Kanekiyo, Shoichi Hazama, and Hiroaki Nagano
Subjects: 0301 basic medicine, Oncology, Cisplatin, Cancer Research, medicine.medical_specialty, Chemotherapy, Univariate analysis, Oncogene, business.industry, medicine.medical_treatment, Odds ratio, Articles, Esophageal cancer, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Genotype, medicine, Mucositis, business, medicine.drug
Abstract: The purpose of this study was to evaluate the association between tumor necrosis factor (TNF)-α polymorphisms and oral mucositis (OM) from 5-fluorouracil (5-FU) plus cisplatin (CDDP) chemotherapy for esophageal cancer. The rs1799964 polymorphism of TNF-α was genotyped using the tetra-primer amplification refractory mutation system polymerase chain reaction. The experimental group comprised 64 patients who received chemotherapy for esophageal cancer between 1997 and 2004; a total of 106 patients between 2005 and 2013 were investigated as the validation group. Univariate analysis of the experimental group revealed that the TT genotype of TNF-α rs1799964 was significantly higher in patients with grade 1-4 OM compared with the TC/CC genotypes [univariate odds ratio (OR)=4.0; P=0.029]. Similarly, univariate analysis of the validation group revealed that the percentage of the TT genotype was significantly higher in patients with grade 1-4 OM compared with the TC/CC genotypes (OR=2.8; P=0.043). This difference in risk was replicated in the validation cohort. Thus, the TT genotype of TNF-α rs1799964 may be a predictor of chemotherapy-induced OM in patients with esophageal cancer.
Published: 2016

45. Duct-penetrating method for pancreaticojejunostomy using a suture-assistance device around a non-dilated main pancreatic duct

Author: Y. Okamoto, Tomio Ueno, Yoshinori Fujiwara, Hisako Kubota, Shumei Mineta, Mio Uraoka, Atsushi Tsuruta, Y. Watanabe, Masaharu Higashida, and T. Okada
Subjects: Pancreatic duct, medicine.anatomical_structure, Hepatology, business.industry, Gastroenterology, medicine, Anatomy, business, Duct (anatomy)
Published: 2018

46. PS02.214: ANALYSIS OF PROGNOSTIC FACTORS IN RECURRENCE CASES AFTER SURGERY FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Author: Shigeru Takeda, Nobuaki Suzuki, Hiroaki Nagano, Yukio Tokumitsu, Michihisa Iida, Mitsuo Nishiyama, Tomio Ueno, Yoshihiro Tokuhisa, Shigefumi Yoshino, Masahiro Kitahara, Shoichi Hazama, Shinobu Tomochika, and Shinsuke Kanekiyo
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Gastroenterology, medicine, General Medicine, business, Esophageal squamous cell carcinoma
Abstract: Background Esophageal cancer is one of the most malignant gastrointestinal cancers and prognosis in recurrent cases remains extremely poor. However some studies show a relatively favorable prognosis among patients with solitary recurrence site who undergo locoregional therapy. It is important to clarify prognostic factors in postrecurrence cases. Methods This study included 156 patients who underwent curative resection for esophageal squamous cell carcinoma from January 2005 to December 2014. In this retrospective study we analysed relationship between clinicopathologic factors and prognosis after recurrence among these 156 patients. Results The average age was 65.2 years (± 8.2), 34 males, 11 females, The frequency of recurrence is pStage I: 2/36 cases (5.6%), pStage II: 7/48 cases (15%), pStage III: 21/43 cases (49%), pStage IVa: 8/11 cases (73%). Median survival time after recurrence was 377 (29 - 3266 days), and a 1 year/2 years/3 year survival rate after relapse was 50%/24%/11%. Patients with recurrent disease were offered treatment with chemotherapy + surgery (5 cases, 11%), chemotherapy + radiation (17 cases, 38%), chemotherapy (18 cases, 40%) and BSC (5 cases, 11%). MST was not reached in the chemotherapy + surgery group (741- 3266 days), 431 days (91–2324 days) in the chemotherapy + radiation group, 223 days (85–1079 days) in the chemotherapy group, and 52 days in the BSC group. There was a significant difference between each groups (P 65) single/multiple site recurrence, presence or absence of postoperative pneumonia, presence or absence of ARDS was selected as a prognostic factor after recurrence. In multivariate analysis, single/multiple site recurrence(HR 10.2, 95%CI 2.619–39.8, P = 0.0008), Postoperative pneumonia (HR 3.6, 95% CI 1.186 - 10.867, P = 0.024), postoperative ARDS (HR 5.6, 95% CI 1.209 - 26, 3, P = 0.0276) was selected. Conclusion Postoperative pulmonary complications might be related and aggressive local control for single site recurrence might improve the prognosis after recurrence of thoracic esophageal squamous cell carcinoma. Disclosure All authors have declared no conflicts of interest.
Published: 2018

47. Duct penetrating method (DPM) for pancreatojejunostomy with an internal stent placement by 'push & pull technique'

Author: Mio Uraoka, Yasuo Oka, Shumei Mineta, M. Nakatani, Hisako Kubota, Yoshinori Fujiwara, T. Okada, Y. Okamoto, Atsushi Tsuruta, Y. Watanabe, Masaharu Higashida, and Tomio Ueno
Subjects: medicine.medical_specialty, Stent placement, medicine.anatomical_structure, Hepatology, business.industry, Gastroenterology, medicine, business, Duct (anatomy), Push pull, Surgery
Published: 2018

48. Poor prognosis of hypermutant colorectal cancer with KRAS mutations: A retrospective analysis of 1,052 Japanese colorectal cancer patients without treatment of immuno-checkpoint inhibitors

Author: Takashi Kawai, Y. Katata, Masahiro Yamamura, Makoto Okawaki, Akihiro Nyuya, Atsushi Tsuruta, Kazuya Yasui, Tomio Ueno, Yoshiko Mori, Yuzo Umeda, Hiroaki Tanioka, Yoshiyuki Yamaguchi, Takeshi Nagasaka, and Toshiaki Toshima
Subjects: Oncology, medicine.medical_specialty, Poor prognosis, Cell cycle checkpoint, business.industry, Colorectal cancer, Immune checkpoint inhibitors, Hematology, medicine.disease_cause, medicine.disease, Internal medicine, Mutation (genetic algorithm), medicine, Retrospective analysis, KRAS, business
Published: 2019

49. Src Family Kinase Inhibition as a Novel Strategy to Augment Melphalan-Based Regional Chemotherapy of Advanced Extremity Melanoma

Author: Tomio Ueno, Ryan S. Turley, Yoshihiro Tokuhisa, Michael E. Lidsky, Hiroaki Toshimitsu, Ketan Sharma, Douglas S. Tyler, Georgia M. Beasley, and Christina K. Augustine
Subjects: Melphalan, medicine.medical_treatment, Blotting, Western, Dasatinib, Apoptosis, Real-Time Polymerase Chain Reaction, Article, Rats, Nude, hemic and lymphatic diseases, Tumor Cells, Cultured, medicine, Animals, Humans, Src family kinase, Antineoplastic Agents, Alkylating, Melanoma, Protein Kinase Inhibitors, neoplasms, Cell Proliferation, Chemotherapy, ABL, Kinase, business.industry, medicine.disease, Xenograft Model Antitumor Assays, Rats, Proto-Oncogene Proteins c-kit, Thiazoles, Pyrimidines, src-Family Kinases, Oncology, Mutation, Cancer research, Female, Surgery, business, medicine.drug, Proto-oncogene tyrosine-protein kinase Src
Abstract: Src kinase inhibition has been shown to augment the efficacy of chemotherapy. Dasatinib, a dual Src/Abl kinase inhibitor approved for the treatment of CML, is under investigation as monotherapy for tumors with abnormal Src signaling, such as melanoma. The goal of this study was to determine if Src kinase inhibition using dasatinib could enhance the efficacy of regionally administered melphalan in advanced extremity melanoma.The mutational status of c-kit and patterns of gene expression predictive of dysregulated Src kinase signaling were evaluated in a panel of 26 human melanoma cell lines. The effectiveness of dasatinib was measured by quantifying protein expression and activation of Src kinase, focal adhesion kinase, and Crk-associated substrate (p130(CAS)), in conjunction with in vitro cell viability assays using seven melanoma cell lines. Utilizing a rat model of regional chemotherapy, we evaluated the effectiveness of systemic dasatinib in conjunction with regional melphalan against the human melanoma cell line, DM443, grown as a xenograft.Only the WM3211 cell line harbored a c-kit mutation. Significant correlation was observed between Src-predicted dysregulation by gene expression and sensitivity to dasatinib in vitro. Tumor doubling time for DM443 xenografts treated with systemic dasatinib in combination with regional melphalan (44.8 days) was significantly longer (p = 0.007) than either dasatinib (21.3 days) or melphalan alone (24.7 days).Systemic dasatinib prior to melphalan-based regional chemotherapy markedly improves the efficacy of this alkylating agent in this melanoma xenograft model. Validation of this concept should be considered in the context of a regional therapy clinical trial.
Published: 2013

50. Efficacy of ramucirumab in combination with second-line or salvage-line FOLFIRI in patients with metastatic colorectal cancer

Author: Akihiro Nyuya, Tomio Ueno, Takeshi Nagasaka, Y. Katata, Hiroaki Tanioka, Atsushi Tsuruta, Masahiro Yamamura, Yoshiyuki Yamaguchi, Makoto Okawaki, Toshiaki Toshima, Kunitoshi Shigeyasu, and Yoshiko Mori
Subjects: Oncology, medicine.medical_specialty, business.industry, Colorectal cancer, Hematology, medicine.disease, Ramucirumab, Second line, Internal medicine, FOLFIRI, Medicine, In patient, Line (text file), business
Published: 2018

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