25 results on '"Satoshi Matsukuma"'
Search Results
2. CD4 and FOXP3 as predictive markers for the recurrence of T3/T4a stage II colorectal cancer: applying a novel discrete Bayes decision rule
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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
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Cancer Research ,Oncology ,Genetics ,Humans ,Bayes Theorem ,Forkhead Transcription Factors ,Neoplasm Recurrence, Local ,Colorectal Neoplasms ,Prognosis ,Biomarkers ,Neoplasm Staging - 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.
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- 2022
3. 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
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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
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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.
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- 2020
4. 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
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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
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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.
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- 2020
5. Immune Evasion of Hepatoma Cancer Stem-Like Cells from Natural Killer Cells
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Yuta Kimura, Ryouichi Tsunedomi, Kiyoshi Yoshimura, Satoshi Matsukuma, Yoshitaro Shindo, Hiroto Matsui, Yukio Tokumitsu, Shin Yoshida, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, Tatsuya Ioka, Shoichi Hazama, and Hiroaki Nagano
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Chromium ,Mice, Inbred BALB C ,Carcinoma, Hepatocellular ,Perforin ,Liver Neoplasms ,Mice, Nude ,B7-H1 Antigen ,Killer Cells, Natural ,Mice ,Oncology ,Cell Line, Tumor ,Culture Media, Conditioned ,Animals ,Humans ,RNA ,Surgery ,Immune Evasion - Abstract
Poor prognosis in liver cancer is due to its high frequency of intrahepatic metastasis. Cancer stem-like cells (CSLCs), which possess the properties of stemness, tumor initiation capability, and resistance to therapy, also exhibit metastatic potential. Immune surveillance plays an important role in the accomplishment of metastasis. Herein, the property of immune evasion in CSLCs was investigated.Sphere cells were induced as CSLCs using a sphere induction medium containing neural survival factor-1. The expression of genes involved in immune evasion was determined using RNA-sequencing for sphere and parental cells followed by validation using flow cytometric analysis and ELISA. Susceptibility to natural killer (NK) cell-mediated cytotoxicity was examined by a chromium release assay. A xenograft model using BALB/c nu/nu mice was used to assess tumor growth. Gene set enrichment analysis was performed for interpreting RNA sequencing.The cell surface expressions of PD-L1, PD-L2, and CEACAM1 were upregulated and those of ULBP1 and MICA/MICB were downregulated in SK-sphere, CSLCs derived from SK-HEP-1, compared with that in parental cells. Levels of soluble MICA were elevated in conditioned medium from SK-sphere. Expression of HLA class I was not downregulated in SK-sphere. The susceptibilities to NK cell-mediated killing and secreted perforin were significantly lower in both CSLCs derived from SK-HEP-1 and HLE than in parental cells. Tumors formed upon inoculation of SK-sphere in immunodeficient mice harboring NK cells were larger than those formed upon inoculation of parental cells.Human hepatoma cell line-derived CSLCs may possess immune evasion properties, especially from NK cell-mediated immunity.
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- 2021
6. Elevated expression of RAB3B plays important roles in chemoresistance and metastatic potential of hepatoma cells
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Ryouichi Tsunedomi, Kiyoshi Yoshimura, Yuta Kimura, Mitsuo Nishiyama, Nobuyuki Fujiwara, Satoshi Matsukuma, Shinsuke Kanekiyo, Hiroto Matsui, Yoshitaro Shindo, Yusaku Watanabe, Yukio Tokumitsu, Shin Yoshida, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, Tatsuya Ioka, Shoichi Hazama, and Hiroaki Nagano
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Cancer Research ,Carcinoma, Hepatocellular ,Carcinogenesis ,rab3 GTP-Binding Proteins ,Liver Neoplasms ,Real-Time Polymerase Chain Reaction ,Up-Regulation ,Mice ,Oncology ,Cell Line, Tumor ,Genetics ,Neoplastic Stem Cells ,Animals ,Humans ,Female - Abstract
Background Cancer stem cells (CSCs) are thought to play important roles in carcinogenesis, recurrence, metastasis, and therapy-resistance. We have successfully induced cancer stem-like sphere cells (CSLCs) which possess enhanced chemoresistance and metastatic potential. To enable the development of targeted therapy against CSLCs, we identified a gene responsible for this phenotype in CSLC. Methods Human hepatoma cell line SK-HEP-1 was used for CSLC induction with a unique sphere inducing medium, and HuH-7 cells were used as non-sphere forming cells in the same condition. RNA-sequencing was performed followed by validation with quantitative RT-PCR and western blotting. Knockdown experiments were done by using CRISPR-Cas9 genome-editing, and the rescue experiments were performed using the expressing plasmid vector. Chemoresistance and liver metastasis of the cells, was studied following the splenic injection of cells to severely immune deficient mice and evaluated using the MTS assay. Quantification of exosomes in the medium was done using ELISA. Results RAB3B was identified as an up-regulated gene in both CSLCs and prognostically poor hepatocellular carcinoma (HCC) by RNA-sequencing. RAB3B-KD cells showed altered CSLC phenotypes such as sphere formation, chemoresistance, and metastatic potentials, and those were rescued by RAB3B complementation. Increased exosome secretion was observed in CSLCs, and it was not observed in the RAB3B-KD cells. In addition, the RAB3B expression correlated with the expression of ABCG2, APOE, LEPR, LXN, and TSPAN13. Conclusion The up regulation of RAB3B may play an important role in the chemoresistance and metastatic potential of CSLCs.
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- 2021
7. Antibiotic Usage Reduced Overall Survival by over 70% in Non-small Cell Lung Cancer Patients on Anti-PD-1 Immunotherapy
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Takehiko Sambe, Eisuke Inoue, Satoshi Wada, Atsuo Kuramasu, Robert M. Hoffman, Yoichiro Narikawa, Takuya Tsunoda, Kiyoshi Yoshimura, Junji Tsurutani, Masahiro Hosonuma, Midori Shida, Yuji Kiuchi, Shinichi Kobayashi, Yuya Hirasawa, Ryotaro Ohkuma, Atsushi Horiike, Naoki Uchida, Satoshi Matsukuma, Masakazu Murayama, Hirotsugu Ariizumi, Kazuyuki Hamada, Tomoyuki Ishiguro, and Yutaro Kubota
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Lung Neoplasms ,medicine.drug_class ,medicine.medical_treatment ,Antibiotics ,Cell ,Programmed Cell Death 1 Receptor ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Lung cancer ,Aged ,Retrospective Studies ,Aged, 80 and over ,biology ,business.industry ,Retrospective cohort study ,General Medicine ,Immunotherapy ,Middle Aged ,medicine.disease ,Prognosis ,Anti-Bacterial Agents ,Survival Rate ,medicine.anatomical_structure ,biology.protein ,Drug Therapy, Combination ,Female ,Non small cell ,Antibody ,business ,Follow-Up Studies - Abstract
BACKGROUND/AIM There is an increasing use of immunotherapy for non-small cell lung cancer (NSCLC) patients. The present study analysed the effect of antibiotic use on the outcome of NSCLC patients undergoing treatment with anti-programmed cell death-1 (anti-PD-1) immunotherapy. PATIENTS AND METHODS This was a retrospective study of 69 NSCLC patients. Eighteen out of 69 patients received antibiotics within 21 days before or within 21 days after start of anti-PD-1 therapy. RESULTS Patients treated with anti-PD-1 antibodies receiving antibiotics had greatly decreased objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) compared to those who did not use antibiotics. Multivariate analysis showed that antibiotic treatment of patients on anti-PD-1 antibody therapy was an independent negative predictive factor of PFS; however, it was not a significant independent predictive factor of OS. CONCLUSION Use of antibiotics within 21 days before and after anti-PD-1 treatment initiation in patients with NSCLC strongly reduced OS and PFS, suggesting the two treatments should not be combined.
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- 2021
8. The impact of peritoneal lavage cytology in biliary tract cancer (KHBO1701): Kansai Hepato-Biliary Oncology Group
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Kenjiro Iida, Akihito Tsuji, Terumasa Yamada, Kenichi Yoshimura, Satoshi Matsukuma, Etsuro Hatano, Daisuke Tsugawa, Shogo Kobayashi, Hiroyuki Okuyama, Shinsuke Nakashima, Yutaka Takeda, Hiroaki Nagano, Yoshiaki Ohmura, Atsushi Miyamoto, Tetsuo Ajiki, Hidetoshi Eguchi, Hiroshi Wada, Tatsuya Ioka, and Satoru Seo
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Curative resection ,Male ,Cancer Research ,medicine.medical_specialty ,CA-19-9 Antigen ,peritoneal metastatic recurrence ,Gastroenterology ,Disease-Free Survival ,Japan ,Clinical Study Report ,Internal medicine ,Cytology ,Overall survival ,cytology‐positive peritoneal lavage ,Medicine ,Humans ,Neoplasm Invasiveness ,Peritoneal Lavage ,Peritoneal Neoplasms ,Aged ,Retrospective Studies ,Biliary tract cancer ,business.industry ,Incidence (epidemiology) ,Incidence ,Retrospective cohort study ,Clinical Study Reports ,Middle Aged ,Prognosis ,Biliary Tract Neoplasms ,Oncology ,Biliary tract ,Female ,Neoplasm Recurrence, Local ,Peritoneum ,business ,cholangiocarcinoma ,Carbohydrate antigen - Abstract
Background Only few studies in literature have analyzed the clinical effects of peritoneal lavage status in biliary tract cancers. Aim We aimed to assess the effect of cytology-positive peritoneal lavage on survival for patients with biliary tract cancer who underwent curative resection. Methods The KHBO1701 study was a multi-institutional retrospective study that assessed the clinical effects of peritoneal lavage cytology in biliary tract cancers. Using clinicopathological data from 11 Japanese institutions, we compared long-term outcomes between patients with cytology-positive and cytology-negative peritoneal lavage. Results Of 169 patients who underwent curative resection, 164 were cytology-negative, and five were cytology-positive. The incidence of portal invasion and preoperative carbohydrate antigen 19-9 levels were higher in the cytology-positive group than in the cytology-negative group. The incidence of peritoneal metastatic recurrence was also higher, and overall survival tended to be worse in the cytology-positive group. In contrast, recurrence-free survival was similar between the cytology-negative and cytology-positive groups. Conclusions The positive status of peritoneal lavage cytology could moderately affect the survival of patients with biliary tract cancers. Given that surgical resection is the only curative treatment option, it may be acceptable to resect biliary tract cancers without other non-curative factors, regardless of peritoneal lavage cytology status.
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- 2020
9. Laparoscopic total biopsy for suspected gallbladder cancer: A case series
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Satoshi Matsukuma, Masao Nakajima, Yoshitaro Shindo, Yukio Tokumitsu, Hiroaki Nagano, Michihisa Iida, Nobuaki Suzuki, Shin Yoshida, Shigeru Takeda, and Hiroto Matsui
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Laparoscopic surgery ,medicine.medical_specialty ,medicine.medical_treatment ,Perforation (oil well) ,gallbladder cancer ,medicine ,Gallbladder cancer ,Research Articles ,whole‐layer cholecystectomy ,business.industry ,Gallbladder ,Cancer ,General Medicine ,Perioperative ,gallbladder bed dissection ,Total biopsy ,medicine.disease ,laparoscopic surgery ,medicine.anatomical_structure ,Oncology ,Medicine ,Cholecystectomy ,Lymphadenectomy ,Surgery ,Radiology ,business ,Research Article - Abstract
Background and aims Imaging diagnosis of gallbladder cancer remains difficult to achieve preoperatively. We developed a novel approach based on laparoscopic whole‐layer cholecystectomy (LWLC) and laparoscopic gallbladder bed dissection (LGBD) for total biopsy, for ultimately determining the optimal treatment strategy for suspected gallbladder cancer detected on preoperative imaging. Here, we describe a case series of patients who underwent this procedure at our institution. Methods We retrospectively examined clinicopathological data of consecutive patients with suspected gallbladder carcinoma at Yamaguchi University Graduate School of Medicine from September 2016 to July 2018 on which a laparoscopic approach was used. Preoperative imaging findings suggestive of gallbladder cancer were defined as follows: elevated lesion >10 mm in diameter, increasing tumor size over time compared with the previous imaging, sessile lesion, irregular wall thickness lesion mimicking cancer, elevated lesion with dense enhancement, or positive results on fluorodeoxyglucose positron emission tomography. LWLC was performed for early‐stage or suspected malignant lesions without liver invasion, and LGBD was performed for lesions with an unclear border between the gallbladder and the liver. When postoperative pathological examination revealed the presence of gallbladder cancer invading into the subserosal layer, additional gallbladder bed resection and regional lymphadenectomy were considered. Patient characteristics, perioperative findings, pathological findings, and postoperative outcomes of patients who underwent LWLC or LGBD were reviewed retrospectively, and the short‐term outcomes of the laparoscopic approach were analyzed. Results Fifteen consecutive patients were included in the study. The median age of the patients was 63 years (IQR 42‐76 years); 7 patients were males. We performed LWLC in 12 cases and LBGD in 3 cases. Median (IQR) operation time was 159 (140‐193) min and median blood loss was 10 (5–30) mL. No bile leakage caused by intraoperative perforation of the gallbladder was seen. Median hospital stay was 7 (5–9) days. Only one patient developed postoperative complications (abdominal abscess). Histologically, gallbladder cancer was diagnosed in five cases (pT1a, n = 2; pT2, n = 3), and two of the pT2 patients underwent additional open surgery. Conclusions Our laparoscopic‐based approach for suspected gallbladder cancer might represent a safe strategy and could play an important role in defining the optimal treatment strategy.
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- 2020
10. Siglec-7 is a predictive biomarker for the efficacy of cancer vaccination against metastatic colorectal cancer
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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
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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.
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- 2020
11. Serum LOX-1 is a novel prognostic biomarker of colorectal cancer
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Chiyo Nakashima-Nakasuga, Yoshitaro Shindo, Shoichi Hazama, Shinobu Tomochika, Michihisa Iida, Shin Yoshida, Yuki Nakagami, Nobuaki Suzuki, Shigeru Takeda, Yoshinobu Hoshii, Hiroyuki Ogihara, Yoshihiko Hamamoto, Tomio Ueno, Hiroto Matsui, Shigefumi Yoshino, Ryouichi Tsunedomi, Ming Xu, Nobuyuki Fujiwara, Shinsuke Kanekiyo, Satoshi Matsukuma, Hiroaki Nagano, Noriko Maeda, and Yukio Tokumitsu
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0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Colorectal cancer ,Neutrophils ,Lymphocyte ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Lymphocyte Count ,Liquid biopsy ,Aged ,business.industry ,Hazard ratio ,Cancer ,Reproducibility of Results ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Scavenger Receptors, Class E ,Blood proteins ,030104 developmental biology ,medicine.anatomical_structure ,ROC Curve ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Biomarker (medicine) ,Surgery ,Female ,business ,Colorectal Neoplasms - Abstract
Background Colorectal cancer is the third most common cancer worldwide. If biomarkers can be identified in liquid biopsy, diagnosis and treatment can be optimized even when cancerous tissues are not available. The purpose of this study was to identify proteins from liquid biopsy that would be useful as markers of poor prognosis. Methods First, we comprehensively analyzed serum proteins to identify potential biomarkers and focused on serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). The relationship between LOX-1 and the prognosis of patients with colorectal cancer has not been reported. Next, we validated this marker using serum samples from 238 patients with colorectal cancer by ELISA and 100 tissue samples by immunohistochemical staining. Results The optimal cut-off value of serum LOX-1 was 538.7 pg/mL according to time-dependent receiver operating characteristics curve analysis. The overall survival of patients with high levels of serum LOX-1 was significantly poorer than that of individuals with low levels of LOX-1 in the training and test datasets. In multivariate analysis for overall survival, serum LOX-1 was an independent prognostic factor identified in liquid biopsy (hazard ratio = 1.729, p = 0.027). The prognosis of patients with high LOX-1 expression in tumor tissues was significantly poorer than that of individuals with low expression (p =0.047 ). Additionally, inflammatory factors such as white blood cell count, C-reactive protein level, neutrophil/lymphocyte ratio, and monocyte/lymphocyte ratio were significantly higher in the group with high serum LOX-1 levels. Conclusions Serum LOX-1 might be a useful biomarker of poor prognosis in colorectal cancer.
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- 2019
12. P48-8 A case of primary lung cancer that led to the diagnosis of SMARCA4-deficient thoracic sarcoid tumor by oncogene panel testing
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Seigo Nakamura, Takuya Tsunoda, Satoshi Matsukuma, Ryotaro Ohkuma, Kengo Takeuchi, Hirotsugu Ariizumi, Atsushi Horiike, Shunji Takahashi, Junji Tsurutani, Satoshi Wada, Nana Iriguchi, Yutaro Kubota, Kiyoshi Yoshimura, Shigetoshi Nishihara, Toshiko Yamochi, Reiko Yoshida, Tomoyuki Ishiguro, and Ryosuke Hanaoka
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Primary (chemistry) ,Oncology ,Oncogene ,business.industry ,SMARCA4 ,Cancer research ,Medicine ,Hematology ,business ,Lung cancer ,medicine.disease - Published
- 2021
13. Postoperative Adjuvant Therapy for Resectable Pancreatic Cancer With Gemcitabine and Adoptive Immunotherapy
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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
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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.
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- 2017
14. Calreticulin is highly expressed in pancreatic cancer stem‐like cells
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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
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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.
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- 2016
15. Cancer stem-like phenotypes including immune surveillance and its responsible genes in induced liver cancer stem-like cells
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Nobuaki Suzuki, Shinobu Tomochika, Michihisa Iida, Hiroaki Nagano, S. Hazama, Yukio Tokumitsu, Satoshi Matsukuma, Kiyoshi Yoshimura, Yuta Kimura, Ryouichi Tsunedomi, Mitsuo Nishiyama, S. Yoshino, and Shigeru Takeda
- Subjects
business.industry ,Cancer ,Hematology ,medicine.disease ,medicine.disease_cause ,Metastasis ,Blot ,Oncology ,Cancer stem cell ,Cell culture ,Interferon ,Cancer research ,Medicine ,business ,Liver cancer ,Carcinogenesis ,medicine.drug - Abstract
Background Cancer stem cells are thought to play important roles in carcinogenesis, recurrence, metastasis, and therapy-resistance. We have successfully induced cancer stem-like sphere cells (CSLCs) from hepatoma cell lines using a unique medium. Methods The human hepatoma cell line SK-HEP-1 was used as parental cells for CSLC induction. To assess the chemoresistance and liver metastasis, MTS assay and splenic injection were performed, respectively. RNA-seq analysis followed by gene set enrichment analysis (GSEA) was performed with cell line derivatives and clinical specimens of hepatoma. Protein expressions were conducted by western blotting, flow-cytometry, or ELISA. Knock-out experiments was accomplished by CRISPR-Cas9 genome-editing. Following rescue experiments were performed with an expression vector. Results The obtained CSLCs showed increased metastatic potentials and resistance to anti-cancer drugs including molecularly targeted drugs for liver cancer. Regarding immune resistance, CSLCs showed increased proportion of positive cells for PD-L1 and PD-L2. In contrast to decreased membrane-bound MICA/MICB, increased soluble MICA in the medium were observed in CSLCs compared to those from the parental cells. As a result of integrated analysis with RNA-seq, a RAB3B was identified as an up-regulated gene in both CSLCs and poor prognostic liver cancers. Mono-allelic RAB3B knock-out cells showed altered sphere formation, significantly lower chemoresistance, and metastatic potential than that of parental cells, and those were rescued by the complementation of RAB3B. The knock-out cells also showed decreased PD-L1 and PD-L2 expressions in sphere induction medium than those in cells cultured with normal medium. GSEA following RNA-seq with the derivative cells revealed that negative enrichment of G2M checkpoint and positive enrichment of interferon response in CSLCs. Conclusions Our induced CSLCs showed characteristic phenotypes such as metastatic ability, chemo- and immune-resistances. The up-regulation of RAB3B may plays important roles in CSLCs. Legal entity responsible for the study Ryouichi TSUNEDOMI. Funding Japan Society for the Promotion of Science. Disclosure All authors have declared no conflicts of interest.
- Published
- 2019
16. 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
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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
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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
17. The Recent Development of the Surgical Treatment for Hepatocellular Carcinoma
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Shigeru Takeda, Satoshi Matsukuma, Nobuaki Suzuki, Hiroto Matsui, Tatsuya Ioka, Hiroaki Nagano, Yukio Tokumitsu, Masao Nakajima, Yoshitaro Shindo, and Michihisa Iida
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Hepatitis C virus ,multiple tumors ,030230 surgery ,Liver transplantation ,DIRECT ACTING ANTIVIRALS ,medicine.disease_cause ,lcsh:Technology ,portal vein tumor thrombus ,lcsh:Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Asian country ,General Materials Science ,Surgical treatment ,lcsh:QH301-705.5 ,neoplasms ,Instrumentation ,Fluid Flow and Transfer Processes ,Performance status ,lcsh:T ,business.industry ,Process Chemistry and Technology ,General Engineering ,hepatic vein tumor thrombus ,multidisciplinary treatment ,hepatocellular carcinoma ,medicine.disease ,lcsh:QC1-999 ,digestive system diseases ,Computer Science Applications ,surgical indication ,lcsh:Biology (General) ,lcsh:QD1-999 ,lcsh:TA1-2040 ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,lcsh:Engineering (General). Civil engineering (General) ,Liver cancer ,business ,lcsh:Physics - Abstract
The optimal treatment for hepatocellular carcinoma (HCC) should be selected based on tumor conditions, liver functional reserve, and performance status. Surgical treatment, such as liver resection and liver transplantation, is the most favorable treatment method; however, its indication criteria differ according to each country’s guidelines. In Western countries, liver resection is indicated only for early-stage HCC patients with Barcelona-Clinic Liver Cancer staging classification (BCLC) 0/A. While in Asian countries, liver resection is one of the treatment options for advanced HCC, such as BCLC B/C. Recently, the treatment of HCC is about to enter a drastic transitional period. It started with the widespread use of minimally invasive surgery for HCC, followed by a high rate of hepatitis C virus eradication with the advent of direct acting antivirals and developing a multidisciplinary treatment for highly advanced HCC. As a result, the importance of liver resection for HCC is increasing, and it is time to reconsider the criteria for selecting treatment methods for HCC patients. This article outlines current topics in the surgical treatment of HCC.
- Published
- 2021
18. 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
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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
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Cancer Research ,Oncology ,Immunology ,Immunology and Allergy - Published
- 2021
19. Cathepsin B is highly expressed in pancreatic cancer stem‑like cells and is associated with patients' surgical outcomes
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Nobuaki Suzuki, Fujimoto Takuya, Atsunori Oga, Kiyoshi Yoshimura, Hiroaki Nagano, Hiroto Matsui, Yasuhiro Fujiwara, Hidetoshi Eguchi, Shogo Kobayashi, Satoshi Matsukuma, Ryouichi Tsunedomi, Nobuyuki Fujiwara, Yukio Tokumitsu, Shoichi Hazama, and Yoshitaro Shindo
- Subjects
cancer stem cells ,0301 basic medicine ,Cancer Research ,cathepsin B ,medicine.medical_treatment ,pancreatic cancer ,Cathepsin B ,Flow cytometry ,Targeted therapy ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Cancer stem cell ,Pancreatic cancer ,medicine ,Oncogene ,medicine.diagnostic_test ,business.industry ,Cancer ,Articles ,medicine.disease ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biomarker ,business - Abstract
Cancer stem-like cells (CSLCs) in solid tumors are resistant to conventional chemotherapy and molecularly targeted therapy, which is thought to contribute to cancer recurrence and metastasis. The present study aimed to identify biomarkers for pancreatic CSLCs (P-CSLCs). Using our previously reported methods, P-CSLC-enriched populations were generated from pancreatic cancer cell lines. The protein expression profiles of these populations were compared with those of parental cells using two-dimensional electrophoresis, tandem mass spectrometry, flow cytometry and immunohistochemistry. Protein expression in surgical specimens was also evaluated for relationships with clinical outcomes. A lysosomal cysteine protease, cathepsin B (CTSB), was significantly upregulated in P-CSLCs compared with that in the parental cells, as shown using western blotting. Flow cytometry analysis also confirmed that CTSB was more highly expressed on the surface of P-CSLCs compared with that on parental cells. Moreover, PCLCs had elevated cellular secretions of CTSB compared with the parental cells. Finally, CTSB expression was evaluated in 69 resected tumor specimens, and high expression was associated with the patients' clinicopathological features and surgical outcomes. The present results suggested that CTSB is a biomarker for poor survival in patients with pancreatic cancer, which is possibly associated with P-CSLCs. This novel biomarker may also have potential as a therapeutic target.
- Published
- 2020
20. Abstract CT251: Immunological and histopathological tumor responses to a novel neoadjuvant peptide vaccine targeting HSP70 and GPC3 antigens in patients with resectable HCC
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Hiroto Matsui, Shiro Akinaga, Satoshi Matsukuma, Yoshitaro Shindo, Akira Saito, Nobuaki Suzuki, Shigeru Takeda, Michihisa Iida, Masao Nakajima, Yuki Nakagami, Shun Doi, Yukio Tokumitsu, Shin Yoshida, Keiko Udaka, Koji Tamada, Ryouichi Tsunedomi, Hiroaki Nagano, Michiie Sakamoto, Shinobu Tomochika, and Shoichi Hazama
- Subjects
Cancer Research ,Tumor microenvironment ,Cellular immunity ,biology ,business.industry ,medicine.medical_treatment ,Immunotherapy ,Immune system ,Oncology ,Antigen ,Peptide vaccine ,medicine ,Cancer research ,biology.protein ,Antibody ,business ,Adjuvant - Abstract
Background: Even with curative resection, the recurrence rate of HCC remains high, and effective adjuvant therapies are not currently available. Our previous Phase I study with novel therapeutic peptides and immune adjuvants demonstrated safety, antigen-specific CTL induction in PBMC, and a sign of efficacy (ASCO 2017 Abstract # 3086). We thus started a Phase I study of the same vaccination therapy as a perioperative immunotherapy setting in patients with resectable HCC (jRCTs061180058). Methods: Two mg each of HLA-A*24:02, 02:01, or 02:06-restricted HSP70- and GPC3-derived peptides, in combination with hLAG-3Ig (1.0 mg) + poly-IC:LC (1.4 mg) were injected intradermally at four sites of the inguinal and axillary regions every week for 6 weeks before surgery. Patients subsequently received 10 injections of adjuvant immunotherapy over 4 months. Surgical specimens and PBMCs were analyzed by mass cytometry (CyTOF), using 66 antibodies to monitor T-cell exhaustion, T-cell activation, and effector Treg induction. Tumor specimens were also subjected to HE staining and immunohistochemical staining for CD3, CD8, PD1, HSP70, and GPC3. Results: Nine patients were treated with preoperative vaccination, and resected surgical specimens and PBMC were examined. Pathohistological analysis revealed three response types: “hot cellular immunity”, “intermediate fumoral immunity”, and “cold response”. In three patients, massive infiltration of CD8+ and PD1+ T cells accompanied necrotic and fibrous regions, in which the targeted tumor antigens HSP70 and GPC3 were highly expressed, representing “hot cellular immunity”. Regarding “intermediate”, three patients showed necrotic regions with infiltrating macrophages. HSP70 and/or GPC3 were also highly expressed, but little infiltration of lymphocytes was evident. In the remaining three patients, “cold response” manifested as tumor comprising a pseudo-glandular pattern with no infiltration of T cells or macrophages. Two of these three patients showed no expression of targeted tumor antigens. CyTOF analysis of the tumors also revealed the percentages of CD3+ cells among live cells and of PD1+ cells among CD8+ cells were extremely low in cold response. However, this trend was not observed in PBMCs, suggesting the critical importance of TIL analysis. Conclusions: This novel therapeutic peptide and immune adjuvant combination induced sustained immune cell infiltration into tumor microenvironments, especially in those presenting target tumor-associated antigens with a non-pseudo-glandular type. Our novel immunotherapy may convert cold tumors into hot tumors containing PD1+ lymphocytes. Combining this novel strategy with PD (L) 1 antibody may be warranted. Citation Format: Masao Nakajima, Shoichi Hazama, Koji Tamada, Keiko Udaka, Shun Doi, Michiie Sakamoto, Akira Saito, Shiro Akinaga, Hiroto Matsui, Yoshitaro Shindo, Satoshi Matsukuma, Yukio Tokumitsu, Shinobu Tomochika, Michihisa Iida, Shin Yoshida, Ryouichi Tsunedomi, Yuki Nakagami, Nobuaki Suzuki, Shigeru Takeda, Hiroaki Nagano. Immunological and histopathological tumor responses to a novel neoadjuvant peptide vaccine targeting HSP70 and GPC3 antigens in patients with resectable HCC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT251.
- Published
- 2020
21. Outcomes following liver resection for multinodular Barcelona Clinic Liver Cancer‑B hepatocellular carcinoma
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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
22. A new prognostic model for hepatocellular carcinoma recurrence after curative hepatectomy
- Author
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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.
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- 2018
23. An accurate prognostic staging system for hepatocellular carcinoma patients after curative hepatectomy
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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
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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
24. Metastatic ability and the epithelial-mesenchymal transition in induced cancer stem-like hepatoma cells
- Author
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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
25. A Case of Metastatic Jejunal Tumor of Large Cell Carcinoma of the Lung Found on Bowel Intussusception
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Kiyoshi Nakayasu, Toshiaki Kamei, Naruzi Kugimiya, Satoru Kurata, Shungo Miyamoto, Masanori Harada, Nobuya Zenpo, Satoshi Matsukuma, and Ryuichiro Suto
- Subjects
Oncology ,medicine.medical_specialty ,Lung ,business.industry ,Large cell ,General Medicine ,medicine.disease ,Gastroenterology ,Bowel intussusception ,medicine.anatomical_structure ,Jejunal Tumor ,Internal medicine ,Carcinoma ,medicine ,business - Abstract
症例は60歳代男性.2003年3月右肺大細胞癌に対し,右中下葉切除術が施行された.当院内科で経過観察中の2006年1月,嘔吐が出現し近医受診.腹部造影CTで小腸腫瘤を先進部とする腸重積および腸間膜,肝十二指腸靭帯,大動脈周囲のリンパ節腫大を認め,当科紹介入院となった.イレウス解除と診断目的に手術を施行した.小腸腫瘍による腸重積とリンパ節による十二指腸から空腸起始部にかけての腸管狭窄を認めたため,小腸腫瘍切除,胃空腸バイパス術を施行した.病理組織検査では肺大細胞癌小腸転移の診断であった.その後,内科にてゲムシタビン(GEM)/シスプラチン(CDDP)併用療法を施行されたが効果を認めなかった.本人の希望もあり,新たな化学療法は施行しない方針とした.
- Published
- 2007
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