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| 1 | Cancer-associated fibroblasts in hepatocellular carcinoma显示文摘The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts(CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines. CAFs crosstalk with cancer cells stimulates tumor progression by creating a favorable microenvironment for progression, invasion, and metastasis through the epithelial-mesenchymal transition. Basic studies on CAFs have advanced, and the role of CAFs in tumors has been elucidated. In particular, for hepatocellular carcinoma, carcinogenesis from cirrhosis is a known fact, and participation of CAFs in carcinogenesis is supported. In this review, we discuss the current literature on the role of CAFs and CAF-related signaling in carcinogenesis, crosstalk with cancer cells, immunosuppressive effects, angiogenesis, therapeutic targets, and resistance to chemotherapy. The role of CAFs is important in cancer initiation and progression. CAF-targeted therapy may be effective for suppression not only of fibrosis but also cancer progression. | Norio Kubo Kenichiro Araki Hiroyuki Kuwano Ken Shirabe | 2016 | World Journal of Gastroenterology2016，22，30： | 25 |
| 2 | Xanthogranulomatous cholecystitis:Difficulty in differentiating from gallbladder cancer显示文摘AIM: To compare cases of xanthogranulomatous cholecystitis(XGC) and advanced gallbladder cancer and discuss the differential diagnoses and surgical options.METHODS: From April 2000 to December 2013, 6 XGC patients received extended surgical resections. During the same period, 16 patients were proven to have gallbladder(GB) cancer, according to extended surgical resection. Subjects chosen for analysis in this study were restricted to cases of XGC with indistinct borders with the liver as it is often difficult to distinguish these patients from those with advanced GB cancer. We compared the clinical features and computed tomography findings between XGC and advanced GB cancer. The following clinical features were retrospectively assessed: age, gender, symptoms, and tumor markers. As albumin and the neutrophil/lymphocyte ratio(NLR) are prognostic in several cancers, we compared serum albumin levels and the NLR between the two groups. The computerized tomography findings were used to compare the two diseases, determine the coexistence of gallstones, the pattern of GB thickening(focal or diffuse), the presence of a hypoattenuated intramural nodule, and continuity of the mucosal line.RESULTS: Based on the preoperative image findings, we suspected GB carcinoma in all cases includingXGC in this series. In addition, by pathological examination, we found that the group of patients with XGC developed inflammatory disease after surgery. Patients with XGC tended to have abdominal pain(4/6, 67%). However, there was no significant difference in clinical symptoms, including fever, between the two groups. Serum albumin and NLR were also similar in the two groups. Serum tumor markers, such as carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA19-9), tended to increase in patients with GB cancer. However, no significant differences in tumor markers were identified. On the other hand, gallstones were more frequently observed in patients with XGC(5/6, 83%) than in patients with GB cancer(4/16, 33%)(P = 0.0116). A hypoattenuated intramural nodule was found in 3 patients with XGC(3/6, 50%), but in only 1 patient with GB cancer(1/16, 6%)(P = 0.0024). The GB thickness, continuous mucosal line, and bile duct dilatation showed no significant differences between XGC and GB cancer.CONCLUSION: Although XGC is often difficult to differentiate from GB carcinoma, it is possible to obtain an accurate diagnosis by careful intraoperative gross observation, and several intraoperative frozen sections. | Hideki Suzuki Satoshi Wada Kenichiro Araki Norio Kubo Akira Watanabe Mariko Tsukagoshi Hiroyuki Kuwano | 2015 | World Journal of Gastroenterology2015，21，35： | 18 |
| 3 | Propofol sedation during endoscopic treatment for early gastric cancer compared to midazolam显示文摘Endoscopic submucosal dissection(ESD)has been proposed as the gold standard in the treatment of early gastric cancer because it facilitates a more accurate histological assessment and reduces the risk of tumor recurrence.However,the time course of ESD for large gastric tumors is frequently prolonged because of the tumor size and technical difficulties and typically requires higher doses of sedative and pain-controlling drugs.Sedative or anesthetic drugs such as midazolam or propofol are used during the procedure.Therapeutic endoscopy of early gastric cancers can often be performed with only moderate sedation.Compared with midazolam,propofol has a very fast onset of action,short plasma half-life and time to achieve sedation,faster time to recovery and discharge,and results in higher patient satisfaction.For overall success,maintaining safety and stability not only during the procedure but also subsequently in the recovery room and ward is necessary.In obese patients,it is recommended that the injected dose be based on a calculated standard weight.Cooperation between gastroenterologists,surgeons,and anesthesiologists is imperative for a successful ESD procedure. | Shinsuke Kiriyama Hiroshi Naitoh Hiroyuki Kuwano | 2014 | World Journal of Gastroenterology2014，20，34： | 14 |
| 4 | Epithelial Cell Apoptosis and Lung Remodeling显示文摘Lung epithelium is the primary site of lung damage in various lung diseases.Epithelial cell apoptosis has been considered to be initial event in various lung diseases.Apoptosis signaling is classically composed of two principle pathways.One is a direct pathway from death receptor ligation to caspase cascade activation and cell death.The other pathway triggered by stresses such as drugs,radiation,infectious agents and reactive oxygen species is mediated by mitochondria.Endoplasmic reticulum has also been shown to be the organelle to mediate apoptosis. Epithelial cell death is followed by remodeling processes,which consist of epithelial and fibroblast activation, cytokine production,activation of coagulation pathway,neoangiogenesis,re-epithelialization and fibrosis. Epithelial and mesenchymal interaction plays important roles in these processes.Further understanding of apoptosis signaling and its regulation by novel strategies may lead to effective treatments against various lung diseases.We review the recent advances in the understanding of apoptosis signaling and discuss the involvement of apoptosis in lung remodeling. | Kazuyoshi Kuwano | 2007 | Cellular & Molecular Immunology2007，4，6： | 12 |
| 5 | Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs显示文摘AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. | Hiroki Morita Erito Mochiki Nobuyuki Takahashi Kiyoshi Kawamura Akira Watanabe Toshinaga Sutou Atsushi Ogawa Mitsuhiro Yanai Kyoichi Ogata Takaaki Fujii Tetsuro Ohno Souichi Tsutsumi Takayuki Asao Hiroyuki Kuwano | 2013 | World Journal of Gastroenterology2013，19，39： | 9 |
| 6 | Nuclear heat shock protein 110 expression is associated with poor prognosis and hyperthermo-chemotherapy resistance in gastric cancer patients with peritoneal metastasis显示文摘AIM To investigate the significance of heat shock protein 110(HSP110) in gastric cancer(GC) patients with peritoneal metastasis undergoing hyperthermochemotherapy.METHODS Primary GC patients(n = 14) with peritoneal metastasis or positive peritoneal lavage cytology who underwent distal or total gastrectomy between April 2000 and December 2011 were enrolled in this study. The patients underwent postoperative intraperitoneal hyperthermo-chemotherapy using a Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear HSP110 expression in surgically resected tumors using immunohistochemistry. Additionally, the effect of HSP110 suppression on hyptherthermochemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437. RESULTS HSP110 immnohistochemical staining in 14 GC patients showed that five(35.7%) samples belonged to the low expression group, and nine(64.3%) samples belonged to the high expression group. Progression-free survival was significantly shorter in the HSP110 high-expression group than in the low-expression group(P = 0.0313). However, no significant relationships were identified between HSP110 expression and the clinicopathological characteristics of patients. Furthermore, high HSP110 expression was not an independent prognostic factor in GC patients with peritoneal metastasis(P = 0.0625). HSP110 expression in MKN45 cells was suppressed by KNK437 at the hyperthermic temperature of 43 ℃ in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 ℃, revealed that proliferation was significantly decreased when HSP110 was inhibited by KNK437. Additionally, HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to hyperthermo-chemotherapy in vitro.CONCLUSION The expression of nuclear HSP110 in GC patients might be a new marker of chemosensitivity and a therapeutic target for patients who are tolerant to existing hyperthermo-chemotherapies. | Akiharu Kimura Kyoichi Ogata Bolag Altan Takehiko Yokobori Erito Mochiki Mitsuhiro Yanai Norimichi Kogure Toru Yanoma Masaki Suzuki Tuya Bai Hiroyuki Kuwano | 2017 | World Journal of Gastroenterology2017，23，42： | 5 |
| 7 | Chemical Composition of the Essential Oil of Mastic Gum and their Antibacterial Activity Against Drug-Resistant Helicobacter pylori显示文摘Mastic gum is derived from the tree named Pistacia lentiscus that is grown only in Island Hios of Greek.Since Mastic was first reported to kill Helicobacter pylori(H.pylori)in 1998,there has been no further study to elucidate which component of mastic specifically shows the antimicrobial activity against H.pylori.In this study,we examined which component of mastic gum was responsible for anti-H.pylori activity.We prepared the essential oil of mastic gum and identified 20 constituents by GC–MS analysis.Ten standard components were assayed for anti-H.pylori activity,and it clarified that a-terpineol and(E)-methyl isoeugenol showed the anti-H.pylori activity against four different H.pylori strains that were established from patients with gastritis,gastric ulcer and gastric cancer.These components could be useful to overcome the drug-resistance H.pylori growth in stomach. | Tomofumi Miyamoto Tadayoshi Okimoto Michihiko Kuwano | 2014 | Natural Products and Bioprospecting2014，4，4： | 4 |
| 8 | 治疗肺动脉高压药物赛乐西帕显示文摘1研制背景花生四烯酸(AA)代谢产物中的一个重要成分是前列环素(1,PGl2),主要在血管内皮细胞中生成。PGI:具有多种生理功能,可强效地舒张血管,抑制血小板聚集,还抑制血管平滑肌细胞分化、增殖和迁移。PGl2的这些功能是通过与血管平滑肌细胞、血小板或其他细胞膜上的PGl2受体结合而产生的。PGl2途径的下调可引起一些血管性疾病,例如肺动脉高压。 | 郭宗儒 asaki t kuwano k morrison k | 2018 | 药学学报2018，53，12： | 3 |
| 9 | Spatiotemporal changes of coxsackievirus and adenovirus receptor in rat hearts during postnatal development and in cultured cardiomyocytes of neonatal rat显示文摘 | Takeshi Kashimura Makoto Kodama Yuko Hotta Junichi Hosoya Kaori Yoshida Takuya Ozawa Ritsuo Watanabe Yuji Okura Kiminori Kato Haruo Hanawa Ryozo Kuwano Yoshifusa Aizawa | 2004 | Virchows Archiv2004，，3： | 2 |
| 10 | Evaluation of 18F-2-deoxy-2-fluoro-d-glucose Positron Emission Tomography for Gastric Cancer显示文摘 | Erito Mochiki Hiroyuki Kuwano Hiroyuki Katoh Takayuki Asao Noboru Oriuchi Keigo Endo | 2004 | World Journal of Surgery2004，，3： | 2 |
| 11 | Shaking table tests on the lateral response of a pile buried in liquefied sand显示文摘 | J.R. Dungca J. Kuwano A. Takahashi T. Saruwatari J. Izawa H. Suzuki K. Tokimatsu | 2005 | Soil Dynamics and Earthquake Engineering2005，，2： | 2 |
| 12 | Laparoscopically assisted total gastrectomy with lymph node dissection for upper and middle gastric cancer显示文摘 | Erito Mochiki Yoshitaka Toyomasu Kyouichi Ogata Hiroyuki Andoh Tetsuro Ohno Ryusuke Aihara Takayuki Asao Hiroyuki Kuwano | 2008 | Surgical Endoscopy2008，，9： | 2 |
| 13 | Relationship between clinicopathological features and mucin phenotypes of advanced gastric adenocarcinoma显示文摘AIM: To investigate a relationship between the clinicopathological features and mucin phenotypes in advanced gastric adenocarcinoma (AGA). METHODS: Immunohistochemical staining was performed to determine the mucin phenotypes in 38 patients with differentiated adenocarcinomas (DACs), 9 with signet-ring cell carcinomas (SIGs), and 48 with other diffuse-type adenocarcinomas (non-SIGs) of AGA. The mucin phenotypes were classified into 4 types: gastric (G), gastrointestinal (GI), intestinal, and unclassified. RESULTS: The G-related mucin phenotypes were highly expressed in all the histological subtypes of AGA. The expression of the GI phenotype in SIG patients was lower than that in DAC patients (P = 0.02), and this phenotype was observed in 56% of the non-SIG patients in the intramucosal layer. Among non-SIG cases, the expression of the GI phenotype was significantly higherin patients with extended adenocarcinomas and those with positive rates of lymph node metastasis. There was no difference between the expressions of the G and other GI phenotypes factors. Among DAC and non-SIG patients, there were no differences between the survival rates of the corresponding patient groups. CONCLUSION: The GI phenotype might possess more invasive characteristics than the G phenotype in nonSIG. Neither of the phenotypes indicated a poor prognosis of DAC and non-SIG. | Fumiaki Toki Atsushi Takahashi Ryusuke Aihara Kyoichi Ogata Hiroyuki Ando Tetsuro Ohno Erito Mochiki Hiroyuki Kuwano | 2010 | World Journal of Gastroenterology2010，16，22： | 2 |
| 14 | The Diagnosis and Treatment of Adult Intussusception显示文摘 | Kunio Takeuchi Yasushi Tsuzuki Tetsu Ando Masao Sekihara Takashi Hara Takayuki Kori Hiroyuki Kuwano | 2003 | Journal of Clinical Gastroenterology2003，，1： | 2 |
| 15 | Evaluation of Pharyngeal Function between No Bolus and Bolus Propofol Induced Sedation for Advanced Upper Endoscopy显示文摘 | Shinsuke Kiriyama Hiroshi Naitoh Minoru Fukuchi Takaharu Fukasawa Kana Saito Yuichi Tabe Hayato Yamauchi Tomonori Yoshida Hiroyuki Kuwano Spiros D. Ladas | 2014 | Diagnostic and Therapeutic Endoscopy2014，，： | 2 |
| 16 | Comparison of endoscopic submucosal dissection with laparoscopic-assisted colorectal surgery for early-stage colorectal cancer: a retrospective analysis显示文摘 | S. Kiriyama Y. Saito S. Yamamoto R. Soetikno T. Matsuda T. Nakajima H. Kuwano | 2012 | Endoscopy2012，，11： | 2 |
| 17 | Safe and effective sedation in endoscopic submucosal dissection for early gastric cancer: a randomized comparison between propofol continuous infusion and intermittent midazolam injection显示文摘 | Shinsuke Kiriyama Takuji Gotoda Hiromi Sano Ichiro Oda Fumiya Nishimoto Tetsuro Hirashima Chika Kusano Hiroyuki Kuwano | 2010 | Journal of Gastroenterology2010，，8： | 2 |
| 18 | Analysis on permanent deformation of embankments caused by earthquakes 显示文摘 | Kuwano J Ishihara K Haya H | 1991 | Soils and Foundations1991，31，3： | 1 |
| 19 | Essential roles of the Fas-Fas ligand pathway in the development of pulmonary fibrosis显示文摘 | Kuwano K Hagimoto N Kawasaki M | 1999 | J Clin Invest1999，104，1： | 1 |
| 20 | p53 expression in squamous dysplasia associated with carcinoma of the oesophagus: evidence for field carcinogeeesis显示文摘 | Yasuda M Kuwano H Watanabe M | 2000 | Br J Cancer2000，83，8： | 1 |
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