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9. Downregulation of ROBO4 in Pancreatic Cancer Serves as a Biomarker of Poor Prognosis and Indicates Increased Cell Motility and Proliferation Through Activation of MMP-9

Author

Yamanaka, Masaya, Hayashi, Masamichi, Sonohara, Fuminori, Yamada, Suguru, Tanaka, Haruyoshi, Sakai, Akihiro, Mii, Shinji, Kobayashi, Daigo, Kurimoto, Keisuke, Tanaka, Nobutake, Inokawa, Yoshikuni, Takami, Hideki, Hattori, Norifumi, Kanda, Mitsuro, Tanaka, Chie, Nakayama, Goro, Koike, Masahiko, and Kodera, Yasuhiro

Published
2022
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13. Outcomes of patients with initially unresectable pancreatic cancer who underwent conversion surgery after FOLFIRINOX or gemcitabine plus nab‐paclitaxel chemotherapy: A multicenter retrospective cohort study (PC‐CURE‐1).

Author

Okano, Naohiro, Kawai, Manabu, Ueno, Makoto, Yu, Xianjun, Inoue, Yosuke, Takahashi, Shinichiro, Wang, Wenquan, Takahashi, Hidenori, Okamura, Yukiyasu, Morinaga, Soichiro, Matsumoto, Ippei, Shimizu, Yasuhiro, Yoshida, Kazuhiro, Yamamoto, Tomohisa, Ohtsuka, Masayuki, Inokawa, Yoshikuni, Nara, Satoshi, Tamura, Jun, Shinoda, Satoru, and Yamamoto, Kouji

Abstract

Background: The efficacy and safety of conversion surgery (CS) after FOLFIRINOX or gemcitabine plus nab‐paclitaxel (GnP) chemotherapy in patients with initially unresectable pancreatic cancer (PC) remains unclear. Methods: This multicenter retrospective cohort study enrolled patients, between 2014 and 2018, with initially locally advanced or metastatic PC who were considered candidates for CS following FOLFIRINOX or GnP chemotherapy. They were classified into surgery (207 patients [194 resection and 13 exploratory laparotomy only]) and continued chemotherapy (10 patients, control) groups. The primary endpoint was overall survival (OS) from the day of diagnosis of potentially curative resection on imaging studies, with an expected hazard ratio (HR) of 0.7. Results: OS in the surgery group was longer than that in the control group (HR, 0.47; 95% confidence interval [CI]: 0.24–0.93). The median OS was 34.4 (95% CI: 27.9–43.4) and 19.8 (95% CI: 14.9–31.1) months in the surgery and control groups, respectively. The Clavien‐Dindo grade ≥ IIIa postoperative complication and in‐hospital mortality rates were 19.6% and 0.5%, respectively. Multivariate analysis revealed that preoperative chemotherapy duration was not associated with OS. Conclusions: CS, following a favorable response to FOLFIRINOX or GnP chemotherapy, improved initially unresectable PC prognosis (specifically, OS), regardless of the chemotherapy duration. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Albumin-Globulin Ratio Indicates the Survival Outcome of Pancreatic Cancer Cases Who Underwent Preoperative Treatment and Curative Surgical Resection

Author

Hayashi, Masamichi, Kobayashi, Daigo, Takami, Hideki, Inokawa, Yoshikuni, Tanaka, Nobutake, Kurimoto, Keisuke, Nakanishi, Koki, Umeda, Shinichi, Shimizu, Dai, Hattori, Norifumi, Kanda, Mitsuro, Tanaka, Chie, Nakayama, Goro, Kodera, Yasuhiro, Hayashi, Masamichi, Kobayashi, Daigo, Takami, Hideki, Inokawa, Yoshikuni, Tanaka, Nobutake, Kurimoto, Keisuke, Nakanishi, Koki, Umeda, Shinichi, Shimizu, Dai, Hattori, Norifumi, Kanda, Mitsuro, Tanaka, Chie, Nakayama, Goro, and Kodera, Yasuhiro

Abstract

Background: The pretreatment albumin–globulin ratio (AGR) is a frequently used inflammation-associated factor that has been reported to have associations with the survival outcomes of various malignancies. Methods: We retrospectively analyzed 162 patients with pancreatic cancer who underwent preoperative treatment followed by curative surgery at Nagoya University Hospital between April 2010 and December 2020. Representative nutritional status indicators of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and albumin–globulin ratio (AGR) were calculated for each case. Results: Among pretreatment blood examination parameters, only AGR (cutoff: 1.33) showed a significant difference in overall survival time (OS) and progression-free survival time (PFS) from the beginning of the preoperative treatment. Median PFS was 22.3 mo, in high AGR cases and 17.1 mo, in low AGR cases (P = 0.019). Median OS was 48.7 mo, in high AGR cases and 32.9 mo, in low AGR cases (P = 0.043). Conclusion: High pretreatment AGR may be a favorable prognostic factor for pancreatic cancer patients who received preoperative multimodal therapy followed by curative cancer resection. It may imply that nutritional status and inflammation control before the multimodal treatment affect the survival outcomes of pancreatic cancer cases and needs to be optimized.

Published
2024

21. ASO Visual Abstract: Downregulation of ROBO4 in Pancreatic Cancer Serves as a Biomarker of Poor Prognosis and Indicates Increased Cell Motility and Proliferation Through Activation of MMP-9

Author

Yamanaka, Masaya, Hayashi, Masamichi, Sonohara, Fuminori, Yamada, Suguru, Tanaka, Haruyoshi, Sakai, Akihiro, Mii, Shinji, Kobayashi, Daigo, Kurimoto, Keisuke, Tanaka, Nobutake, Inokawa, Yoshikuni, Takami, Hideki, Hattori, Norifumi, Kanda, Mitsuro, Tanaka, Chie, Nakayama, Goro, Koike, Masahiko, and Kodera, Yasuhiro

Published
2022
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23. Risk Factors for Long-term Body Weight Loss After Proximal Gastrectomy: A Retrospective Analysis

Author

AGATSUMA, YUYA, primary, NAKANISHI, KOKI, additional, TANAKA, CHIE, additional, KANDA, MITSURO, additional, SHIMIZU, DAI, additional, UMEDA, SHINICHI, additional, KURIMOTO, KEISUKE, additional, INOKAWA, YOSHIKUNI, additional, TAKAMI, HIDEKI, additional, HATTORI, NORIFUMI, additional, HAYASHI, MASAMICHI, additional, NAKAYAMA, GORO, additional, FUJIWARA, MICHITAKA, additional, and KODERA, YASUHIRO, additional

Published
2024
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28. Therapeutic antibody targeting natriuretic peptide receptor 1 inhibits gastric cancer growth viaBCL‐2‐mediated intrinsic apoptosis.

Author

Sasahara, Masahiro, Kanda, Mitsuro, Tanaka, Chie, Shimizu, Dai, Umeda, Shinichi, Takami, Hideki, Inokawa, Yoshikuni, Hattori, Norifumi, Hayashi, Masamichi, Nakayama, Goro, and Kodera, Yasuhiro

Subjects
PEPTIDE receptors, STOMACH cancer, TUMOR growth, SMALL interfering RNA, BLOOD proteins, MEMBRANE proteins
Abstract

Despite recent advances in the development of therapeutic antibodies, the prognosis of unresectable or metastatic gastric cancer (GC) remains poor. Here, we searched for genes involved in the malignant phenotype of GC and investigated the potential of one candidate gene to serve as a novel therapeutic target. Analysis of transcriptome datasets of GC identified natriuretic peptide receptor 1 (NPR1), a plasma membrane protein, as a potential target. We employed a panel of human GC cell lines and gene‐specific small interfering RNA‐mediated NPR1 silencing to investigate the roles of NPR1 in malignancy‐associated functions and intracellular signaling pathways. We generated an anti‐NPR1 polyclonal antibody and examined its efficacy in a mouse xenograft model of GC peritoneal dissemination. Associations between NPR1 expression in GC tissue and clinicopathological factors were also evaluated. NPR1 mRNA was significantly upregulated in several GC cell lines compared with normal epithelial cells. NPR1 silencing attenuated GC cell proliferation, invasion, and migration, and additionally induced the intrinsic apoptosis pathway associated with mitochondrial dysfunction and caspase activation via downregulation of BCL‐2. Administration of anti‐NPR1 antibody significantly reduced the number and volume of GC peritoneal tumors in xenografted mice. High expression of NPR1 mRNA in clinical GC specimens was associated with a significantly higher rate of postoperative recurrence and poorer prognosis. NPR1 regulates the intrinsic apoptosis pathway and plays an important role in promoting the GC malignant phenotype. Inhibition of NPR1 with antibodies may have potential as a novel therapeutic modality for unresectable or metastatic GC. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Therapeutic antibody targeting natriuretic peptide receptor 1 inhibits gastric cancer growth viaBCL‐2‐mediated intrinsic apoptosis

Author

Sasahara, Masahiro, primary, Kanda, Mitsuro, additional, Tanaka, Chie, additional, Shimizu, Dai, additional, Umeda, Shinichi, additional, Takami, Hideki, additional, Inokawa, Yoshikuni, additional, Hattori, Norifumi, additional, Hayashi, Masamichi, additional, Nakayama, Goro, additional, and Kodera, Yasuhiro, additional

Published
2023
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30. Increased STX3 transcript and protein levels were associated with poor prognosis in two independent cohorts of esophageal squamous cell carcinoma patients

Author

Shinozuka, Takahiro, primary, Kanda, Mitsuro, additional, Sato, Yusuke, additional, Shimizu, Dai, additional, Tanaka, Chie, additional, Umeda, Shinichi, additional, Inokawa, Yoshikuni, additional, Hattori, Norifumi, additional, Hayashi, Masamichi, additional, Nakayama, Goro, additional, and Kodera, Yasuhiro, additional

Published
2023
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32. 39. HIGH PREOPERATIVE PLATELET TO LYMPHOCYTE RATIO IS ASSOCIATED WITH A GREATER RISK OF POSTOPERATIVE COMPLICATIONS AND RECURRENCES IN ESOPHAGEAL CANCER

Author

Sasahara, Masahiro, primary, Kanda, Mitsuro, additional, Shimizu, Dai, additional, Takami, Hideki, additional, Inokawa, Yoshikuni, additional, Hattori, Norifumi, additional, Hayashi, Masamichi, additional, Tanaka, Chie, additional, Fujiwara, Michitaka, additional, Nakayama, Goro, additional, and Kodera, Yasuhiro, additional

Published
2023
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33. 27. OPLAH PROTEIN EXPRESSION STRATIFIES THE PROGNOSIS OF PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS

Author

Shimizu, Dai, primary, Kanda, Mitsuro, additional, Nakanishi, Koki, additional, Kurimoto, Keisuke, additional, Umeda, Shinichi, additional, Takami, Hideki, additional, Inokawa, Yoshikuni, additional, Hattori, Norifumi, additional, Hayashi, Masamichi, additional, Sato, Yusuke, additional, Tanaka, Chie, additional, Nakayama, Goro, additional, Fujiwara, Michitaka, additional, and Kodera, Yasuhiro, additional

Published
2023
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34. OPLAH Protein Expression Stratifies the Prognosis of Patients With Squamous Cell Carcinoma of the Esophagus

Author

SHIMIZU, DAI, KANDA, MITSURO, KISHIDA, TAKAYOSHI, NAKAMURA, SHUNSUKE, SASAHARA, MASAHIRO, UEDA, SEI, SATO, YUSUKE, INOKAWA, YOSHIKUNI, HATTORI, NORIFUMI, HAYASHI, MASAMICHI, TANAKA, CHIE, MOTOYAMA, SATORU, and KODERA, YASUHIRO

Subjects
Research Article
Abstract

Background/Aim: Squamous cell carcinoma is one of the major subtypes of esophageal carcinoma, and the 5-year overall survival rate of esophageal squamous cell carcinoma patients who underwent curative treatment remains below 40%. We aimed to detect and validate the prognosticators of esophageal squamous cell carcinoma in patients who underwent radical esophagectomy. Materials and Methods: Comprehensive analysis of transcriptome and clinical data from The Cancer Genome Atlas revealed OPLAH as one of the differentially expressed genes between esophageal squamous cell carcinoma tissues and normal esophageal mucosa. OPLAH expression changes were significantly associated with a patient prognosis. OPLAH protein levels were further evaluated by immunohisto-chemistry in esophageal squamous cell carcinoma tissues (n=177) as well as in serum samples (n=54) using ELISA. Results: OPLAH mRNA was significantly overexpressed in esophageal squamous cell carcinoma tissues compared to normal esophageal mucosa, and patients with high OPLAH mRNA expression have a significantly poorer prognosis, according to The Cancer Genome Atlas data. The high staining intensity of OPLAH protein in esophageal squamous cell carcinoma tissue clearly stratified patient prognosis. According to multivariable analysis, high OPLAH protein expression was an independent prognostic factor for survival after surgery. Pre-neoadjuvant chemotherapy serum OPLAH protein concentrations were significantly associated with clinical tumor depth and node positivity and, consequently, with advanced clinical stage. The serum OPLAH protein concentration was significantly decreased by neoadjuvant chemotherapy. Conclusion: OPLAH protein expression in cancerous tissue and serum may have clinical utility towards stratifying prognosis of patients with esophageal squamous cell carcinoma.

Published
2023

35. Supplementary Data from Concurrent Targeting of Potential Cancer Stem Cells Regulating Pathways Sensitizes Lung Adenocarcinoma to Standard Chemotherapy

Author

Shibata, Masahiro, primary, Ooki, Akira, primary, Inokawa, Yoshikuni, primary, Sadhukhan, Pritam, primary, Ugurlu, M. Talha, primary, Izumchenko, Evgeny, primary, Munari, Enrico, primary, Bogina, Giuseppe, primary, Rudin, Charles M., primary, Gabrielson, Edward, primary, Singh, Anju, primary, and Hoque, Mohammad O., primary

Published
2023
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36. Data from Concurrent Targeting of Potential Cancer Stem Cells Regulating Pathways Sensitizes Lung Adenocarcinoma to Standard Chemotherapy

Author

Shibata, Masahiro, primary, Ooki, Akira, primary, Inokawa, Yoshikuni, primary, Sadhukhan, Pritam, primary, Ugurlu, M. Talha, primary, Izumchenko, Evgeny, primary, Munari, Enrico, primary, Bogina, Giuseppe, primary, Rudin, Charles M., primary, Gabrielson, Edward, primary, Singh, Anju, primary, and Hoque, Mohammad O., primary

Published
2023
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37. Predictive impacts of peritoneal washing cytology for surgical resection‐intended pancreatic cancer cases: Establishment of planned staging laparoscopy criteria.

Author

Tanaka, Nobutake, Takami, Hideki, Hayashi, Masamichi, Inokawa, Yoshikuni, Kurimoto, Keisuke, Hattori, Norifumi, Kanda, Mitsuro, Tanaka, Chie, Nakayama, Goro, and Kodera, Yasuhiro

Abstract

Background: Staging laparoscopy (SL) has been advocated for pancreatic cancer, mainly to evaluate the peritoneal washing cytology (CY) status, which seems to impact the prognosis of pancreatic cancer. To establish an optimal treatment strategy for CY positive (CY+) pancreatic cancer cases, real‐world clinical data about CY status‐depending surgical outcomes should be accumulated. Methods: Peritoneal washing samples were collected from 183 consecutive patients who could be classified as either resectable or borderline resectable (BR) pancreatic cancer between January 2012 and December 2020. Correlations between the CY status and other clinicopathological parameters with the recurrence patterns and survival outcomes were examined. In addition, we analyzed several risk factors for the CY+ status and attempted to identify the patient population that may benefit most from SL. Results: A total of 24 of the 183 patients were CY+. Peritoneal recurrence occurred more frequently in CY+ cases than in CY− cases (29% vs. 6%, p <.001) and median survival time after surgery was significantly shorter in CY+ cases than in CY− cases (28.5 months vs. 67.5 months; p <.001). In detail, almost all CY+ patients among curative resection‐intended cases had either elevated preoperative serum CA19‐9 levels (≥250 U/mL) or DUPAN‐2 levels (≥150 U/mL). Significant predictive factors of CY positivity were BR status (p =.028) and serum CA19‐9 level exceeding 250 U/mL (p =.008). Conclusion: CY status was identified as an independent prognostic factor, and SL examination should be recommended, especially for patients with risk factors for CY positivity, such as BR cancer and elevated serum CA19‐9 levels. [ABSTRACT FROM AUTHOR]

Published
2023
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38. High Preoperative Platelet to Lymphocyte Ratio is Associated with a Greater Risk of Postoperative Complications and Hematogenous Recurrences in Esophageal Squamous Cell Carcinoma Patients Receiving Neoadjuvant Treatment

Author

Sasahara, Masahiro, primary, Kanda, Mitsuro, additional, Shimizu, Dai, additional, Takami, Hideki, additional, Inokawa, Yoshikuni, additional, Hattori, Norifumi, additional, Hayashi, Masamichi, additional, Tanaka, Chie, additional, Fujiwara, Michitaka, additional, Nakayama, Goro, additional, and Kodera, Yasuhiro, additional

Published
2023
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39. Perioperative changes in geriatric functions of elderly patients undergoing surgical resection for gastric cancer.

Author

Tanaka, Chie, primary, Kanda, Mitsuro, additional, Nakanishi, Koki, additional, Umeda, Shinichi, additional, Shimizu, Dai, additional, Inokawa, Yoshikuni, additional, Takami, Hideki, additional, Hayashi, Masamichi, additional, Nakayama, Goro, additional, Fujiwara, Michitaka, additional, Kodera, Yasuhiro, additional, and Hattori, Norifumi, additional

Published
2023
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40. Proposal of a coagulation score to predict postoperative survival of patients undergoing neoadjuvant therapy followed by subtotal esophagectomy for squamous cell carcinoma of the esophagus.

Author

Sugiyama, Fumitake, primary, Shimizu, Dai, additional, Kanda, Mitsuro, additional, Tanaka, Chie, additional, Takami, Hideki, additional, Inokawa, Yoshikuni, additional, Hattori, Norifumi, additional, Hayashi, Masamichi, additional, Nakayama, Goro, additional, Fujiwara, Michitaka, additional, and Kodera, Yasuhiro, additional

Published
2023
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42. OPLAH Protein Expression Stratifies the Prognosis of Patients With Squamous Cell Carcinoma of the Esophagus

Author

SHIMIZU, DAI, primary, KANDA, MITSURO, additional, KISHIDA, TAKAYOSHI, additional, NAKAMURA, SHUNSUKE, additional, SASAHARA, MASAHIRO, additional, UEDA, SEI, additional, SATO, YUSUKE, additional, INOKAWA, YOSHIKUNI, additional, HATTORI, NORIFUMI, additional, HAYASHI, MASAMICHI, additional, TANAKA, CHIE, additional, MOTOYAMA, SATORU, additional, and KODERA, YASUHIRO, additional

Published
2023
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44. Controlling Nutritional Status Score Serves as a Prognosticator in Esophageal Squamous Cell Carcinoma: Optimal Timing of Evaluation of Patients Undergoing Neoadjuvant Treatment

Author

Nonogaki, Ikue, primary, Kanda, Mitsuro, additional, Shimizu, Dai, additional, Inokawa, Yoshikuni, additional, Hattori, Norifumi, additional, Hayashi, Masamichi, additional, Tanaka, Chie, additional, Koike, Masahiko, additional, Nakayama, Goro, additional, and Kodera, Yasuhiro, additional

Published
2022
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45. Double common bile duct associated with pancreaticobiliary maljunction

Author

Yamada, Kenta, Ishikawa, Takuya, Ohno, Eizaburo, Iida, Tadashi, Suzuki, Hirotaka, Uetsuki, Kota, Yashika, Jun, Yoshikawa, Masakatsu, Takami, Hideki, Inokawa, Yoshikuni, Uchida, Hiroo, Kawashima, Hiroki, and Fujishiro, Mitsuhiro

Subjects
double common bile duct, digestive system, pancreaticobiliary maljunction
Abstract

A 45-year-old female was admitted to the hospital with a diagnosis of acute pancreatitis. A computed tomography scan showed two extrahepatic bile ducts. Magnetic resonance cholangiopancreatography sug- gested a stone in one of the bile ducts. Endoscopic retrograde cholangiopancreatography revealed two extrahepatic bile ducts joining at the hilum of the liver accompanied with pancreaticobiliary maljunction. Sphincterotomy was performed and a protein plug was drained from the bile duct. Several treatment options were discussed, and the patient was treated with laparoscopic cholecystectomy without extrahepatic bile duct resection and planned to be followed up considering the risk of carcinogenesis in the bile ducts., This is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view the details of this license, please visit (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Published
2021

47. Comparison Between FOLFIRINOX and nal-IRI/FL as Second-line Treatment After Gemcitabine Plus Nab-paclitaxel for Pancreatic Cancer

Author

OTSU, TOMOHISA, primary, INOKAWA, YOSHIKUNI, additional, TAKAMI, HIDEKI, additional, HAYASHI, MASAMICHI, additional, KURIMOTO, KEISUKE, additional, TANAKA, NOBUTAKE, additional, TANAKA, HARUYOSHI, additional, SHIMIZU, DAI, additional, HATTORI, NORIFUMI, additional, KANDA, MITSURO, additional, TANAKA, CHIE, additional, NAKAYAMA, GORO, additional, and KODERA, YASUHIRO, additional

Published
2022
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