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Role of cyclooxygenase-2 in the carcinogenesis of gastrointestinal tract cancers: A review and report of personal experience 被引量:33
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作者 Takashi Fujimura tetsuo ohta +2 位作者 Katsunobu Oyama Tomoharu Miyashita Koichi Miwa 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第9期1336-1345,共10页
Selective cyclooxygenase (COX)-2 inhibitors (coxibs) were developed as one of the anti-inflammatory drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs (NSAIDs). However, coxibs also... Selective cyclooxygenase (COX)-2 inhibitors (coxibs) were developed as one of the anti-inflammatory drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs (NSAIDs). However, coxibs also have an ability to inhibit tumor development of various kinds the same way that NSAIDs do. Many experimental studies using cell lines and animal models demonstrated an ability to prevent tumor proliferation of COX-2 inhibitors. After performing a randomized study for polyp chemoprevention study in patients with familial adenomatous polyposis (FAP), which showed that the treatment with celecoxib, one of the coxibs, significantly reduced the number of colorectal polyps in 2000, the U.S. Food and Drug Administration (FDA) immediately approved the clinical use of celecoxib for FAP patients. However, some coxibs were recently reported to increase the risk of serious cardiovascular events including heart attack and stroke. In this article we review a role of COX-2 in carcinogenesis of gastrointestinal tract, such as the esophagus, stomach and colorectum, and also analyze the prospect of coxibs for chemoprevention of gastrointestinal tract tumors. 展开更多
关键词 Cyclooxygenase-2 (COX-2) Selective COX-2 inhibitors Esophageal cancer GASTRIC-CANCER Colorectal cancer
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Surgical anatomy of innervation of the gallbladder in humans and Suncus murinus with special reference to morphological understanding of gallstone formation after gastrectomy 被引量:19
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作者 Shuang-Qin Yi tetsuo ohta +7 位作者 Akihiko Tsuchida Hayato Terayama Munekazu Naito Jun Li Heng-Xiao Wang Nozomi Yi Shigenori Tanaka Masahiro Itoh 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第14期2066-2071,共6页
AIM: To clarify the innervation of human gallbladder,with special reference to morphological understanding of gallstone formation after gastrectomy.METHODS: The liver, gallbladder and surrounding structures were imm... AIM: To clarify the innervation of human gallbladder,with special reference to morphological understanding of gallstone formation after gastrectomy.METHODS: The liver, gallbladder and surrounding structures were immersed in a 10 mg/L solution of alizarin red S in ethanol to stain the peripheral nerves in cadavers (n = 10). Innervation in the areas was completely dissected under a binocular microscope. Similarly,innervation in the same areas of 10 Suncus murinus (S. murinus) was examined employing whole mount immunohistochemistry.RESULTS: Innervation of the gallbladder occurred predominantly through two routes. One was from the anterior hepatic plexus, the innervation occurred along the cystic arteries and duct. Invariably this route passed through the hepatoduodenal ligament. The other route was from the posterior hepatic plexus, the innervation occurred along the cystic duct ventrally. This route also passed through the hepatoduodenal ligament dorsally.Similar results were obtained in S. murinus.CONCLUSION: The route from the anterior hepatic plexus via the cystic artery and/or duct is crucial for preserving gallbladder innervation. Lymph node dissection specifically in the hepatoduodenal ligament may affect the incidence of gallstones after gastrectomy.Furthermore, the route from the posterior hepatic plexus via the common bile duct and the cystic duct to the gallbladder should not be disregarded. Preservation of the plexus may attenuate the incidence of gallstone formation after gastrectomy. 展开更多
关键词 INNERVATION GALLSTONE Hepatoduodenalligament GASTRECTOMY Whole mount immunohistochemistry
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Enhancement patterns of pancreatic adenocarcinoma on conventional dynamic multi-detector row CT:Correlation with angiogenesis and fibrosis 被引量:15
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作者 Yuki Hattori Toshifumi Gabata +5 位作者 Osamu Matsui Kentaro Mochizuki Hirohisa Kitagawa Masato Kayahara tetsuo ohta Yasuni Nakanuma 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第25期3114-3121,共8页
AIM:To evaluate retrospectively the correlation between enhancement patterns on dynamic computed tomography (CT) and angiogenesis and fibrosis in pancreatic adenocarcinoma.METHODS: Twenty-three patients with pancreati... AIM:To evaluate retrospectively the correlation between enhancement patterns on dynamic computed tomography (CT) and angiogenesis and fibrosis in pancreatic adenocarcinoma.METHODS: Twenty-three patients with pancreatic adenocarcinoma underwent dynamic CT and tumor resection. In addition to the absolute and relative enhanced value that was calculated by subtracting the attenuation value on pre-contrast from those on contrast-enhanced CT in each phase, we defined one parameter, "tumor-aorta enhancement ratio", which was calculated by dividing enhancement of pancreatic cancer by enhancement of abdominal aorta in each phase. These enhancement patterns were correlated with the level of vascular endothelial growth factor (VEGF), microvessel density (MVD), and extent of fibrosis.RESULTS: The absolute enhanced value in the arterial phase correlated with the level of VEGF and MVD (P=0.047, P=0.001). The relative enhanced value in arterial phase and tumor-aorta enhancement ratio (arterial) correlated with MVD (P=0.003, P=0.022). Tumor-aorta enhancement ratio (arterial) correlated negatively with the extent of fibrosis (P=0.004). The tumors with greater MVD and higher expression of VEGF tended to show high enhancement in the arterial dominant phase. On the other hand, the tumors with a larger amount of fibrosis showed a negative correlation with the grade of enhancement during the arterial phase.CONCLUSION: Enhancement patterns on dynamic CT correlated with angiogenesis and may be modified by the extent of fibrosis. 展开更多
关键词 Computed tomography Contrast media Pancreatic cancer ANGIOGENESIS
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Characterization of CD133^+ parenchymal cells in the liver:Histology and culture 被引量:6
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作者 Seiichi Yoshikawa Yoh Zen +4 位作者 Takahiko Fujii Yasunori Sato tetsuo ohta Yutaka Aoyagi Yasuni Nakanuma 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第39期4896-4906,共11页
AIM: To reveal the characteristics of CD133^+ cells in the liver, METHODS: This study examined the histological characteristics of CD133^+ cells in non-neoplastic and neoplastic liver tissues by immunostaining, an... AIM: To reveal the characteristics of CD133^+ cells in the liver, METHODS: This study examined the histological characteristics of CD133^+ cells in non-neoplastic and neoplastic liver tissues by immunostaining, and also analyzed the biological characteristics of CD133^+ cells derived from human hepatocellular carcinoma (HCC) or cholangiocarcinoma cell lines. RESULTS: Immunostaining reveated constant expression of CD133 in non-neoplastic and neoplastic biliary epithelium, and these cells had the immunophenotype CD133^+/CK19^+/HepPar-1. A small number of CD133^+/CK19/HepPar-1^+ cells were also identified in HCC and combined hepatocellular and cholangiocarcinoma. In addition, small ductal structures, resembling the canal of Hering, partly surrounded by hepatocytes were positive for CD133. CD133 expression was observed in three HCC (HUH7, PLC5 and HepG2) and two cholangiocarcinoma cell lines (HuCCT1 and CCKS1). Fluorescence-activated cell sorting (FACS) revealed that CD133^+ and CD133 cells derived from HuH7 and HuCCT1 cells similarly produced CD133^+ and CD133 cells during subculture. To examine the relationship between CD133^+ cells and the side population (SP) phenotype, FACS was performed using Hoechst 33342 and a monoclonal antibody against CD133. The ratios of CD133^+/CD133 cells were almost identical in the SP and non-SP in HUH7. In addition, four different cellular populations (SP/CD133^+, SP/CD133, nonP/CD133^+, and non- SP/CD133) could similarly produce CD133^+ and CD133- cells during subculture. CONCLUSION: This study revealed that CD133 could be a biliary and progenitor cell marker in vivo. However, CD133 alone is not sufficient to detect tumor-initiating cells in cell lines. 展开更多
关键词 CHOLANGIOCARCINOMA Hepatocellular carcinoma KERATINS Stem cells
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Intraductal papillary neoplasm of the bile duct accompanying biliary mixed adenoneuroendocrine carcinoma 被引量:3
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作者 Ichiro Onishi Hirohisa Kitagawa +12 位作者 Kenichi Harada Syogo Maruzen Seisyo Sakai Isamu Makino Hironori Hayashi Hisatoshi Nakagawara Hidehiro Tajima Hiroyuki Takamura Takashi Tani Masato Kayahara Hiroko Ikeda tetsuo ohta Yasuni Nakanuma 《World Journal of Gastroenterology》 SCIE CAS 2013年第20期3161-3164,共4页
We present the first case of an intraductal papillary neoplasm of the bile duct(IPNB) accompanying a mixed adenoneuroendocrine carcinoma(MANEC).A 74-yearold woman presented with fever of unknown cause.Laboratory data ... We present the first case of an intraductal papillary neoplasm of the bile duct(IPNB) accompanying a mixed adenoneuroendocrine carcinoma(MANEC).A 74-yearold woman presented with fever of unknown cause.Laboratory data revealed jaundice and liver injury.Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct,which exhibited early enhancement and papillary growth.Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater,characterized by its protruding and dilated orifice.Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct,but no invasive region was suggested by diagnostic imaging.Therefore,the initial diagnosis was IPNB.After endoscopic nasobiliary drainage,a pylorus-preserving pancreaticoduodenectomy was performed.Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia,indicating pancreaticobiliary-type IPNB.In addition,solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident.Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component,diagnosing it as a neuroendocrine tumor(NET).Furthermore,the MIB-1 proliferation index of NET was higher than that of IPNB,and microinvasion of the NET component was found,indicating neuroendocrine carcinoma(NET G3).This unique case of MANEC,comprising IPNB and NET,provides insight into the pathogenesis of biliary NET. 展开更多
关键词 NEUROENDOCRINE tumor INTRADUCTAL PAPILLARY NEOPLASM of BILE DUCT INTRADUCTAL PAPILLARY NEOPLASM of the BILE DUCT BILE DUCT
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Intraperitoneal Chemotherapy as a Multimodal Treatment for Gastric Cancer Patients with Peritoneal Metastasis 被引量:16
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作者 Sachio Fushida Katsunobu Oyama +7 位作者 Jun Kinoshita Tomoya Tsukada Kouichi Okamoto Hidehiro Tajima Itasu Ninomiya Hirohisa Kitagawa Takashi Fujimura tetsuo ohta 《Journal of Cancer Therapy》 2013年第9期6-15,共10页
Peritoneal metastasis of gastric cancer is mainly caused by the dispersion of free cancer cells from the serosal surface of the invaded stomach, from surgically transected lymphatic channels, and from tumor cell-conta... Peritoneal metastasis of gastric cancer is mainly caused by the dispersion of free cancer cells from the serosal surface of the invaded stomach, from surgically transected lymphatic channels, and from tumor cell-containing blood from the primary lesion into the peritoneal cavity. Intraperitoneal chemotherapy (IPC) combined with surgery has performed for the prevention and treatment of peritoneal metastasis in gastric cancer. The efficacy of this technique is influenced by the pharmacokinetic advantage achievable with the anticancer drug, timing of administration, combination with hyperthermia, and tumor volume. The pharmacokinetic advantage for peritoneal cavity exposure relative to peripheral circulation by intraperitoneal delivery for drugs including cisplatin (10-fold advantage), mitomycin C (20- to 30-fold advantage), docetaxel (500-fold advantage), and paclitaxel (1000-fold advantage) has been confirmed. To avoid uneven drug distribution in the peritoneal cavity and the re-growth of residual tumor, it seems to be reasonable to perform IPC perioperatively;however, early perioperative intraperitoneal chemotherapy (EPIC) has a relatively high morbidity rate compared with intraoperative IPC. Hyperthermia has both cytotoxicity of itself and a synergistic effect with anticancer drugs, especially mitomycin C. In the adjuvant setting, patients with either hyperthermic intraperitoneal chemotherapy (HIPEC) or EPIC showed a significant improvement of survival compared to those with surgery alone. In addition, extensive intraoperative peritoneal lavage (EIPL) seems also to be a reasonable method to reduce free cancer cells in the peritoneal cavity. For the treatment of peritoneal metastasis, cytoreductive surgery which achieves R0 or R1 resection followed by IPC has demonstrated a survival benefit, whereas gross residual tumor (R2) treated by IPC has shown poor prognosis. Extensive cytoreductive surgery, such as peritonectomy, followed by IPC achieved long-term survival for selected patients, though this aggressive procedure led to high morbidity and mortality rates. It seems that combined chemotherapy (systemically and intraperitoneally) followed by conversion surgery can be expected to be a powerful procedure for the patients with gross peritoneal tumors. 展开更多
关键词 PERITONEAL METASTASIS GASTRIC CANCER INTRAPERITONEAL CHEMOTHERAPY
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Clinical and radiological feature of lymphoepithelial cyst of the pancreas 被引量:4
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作者 Hirofumi Terakawa Isamu Makino +8 位作者 Hisatoshi Nakagawara Tomoharu Miyashita Hidehiro Tajima Hirohisa Kitagawa Takashi Fujimura Dai Inoue Kazuto Kozaka Toshifumi Gabata tetsuo ohta 《World Journal of Gastroenterology》 SCIE CAS 2014年第45期17247-17253,共7页
A lymphoepithelial cyst(LEC)of the pancreas is a rare benign lesion.Because patients with LEC of the pancreas have a good prognosis,it is important that these lesions are accurately differentiated from other more aggr... A lymphoepithelial cyst(LEC)of the pancreas is a rare benign lesion.Because patients with LEC of the pancreas have a good prognosis,it is important that these lesions are accurately differentiated from other more aggressive pancreatic neoplasms for an appropriate treatment strategy.Previous studies have reported that a definitive diagnosis of LEC often cannot be obtained based solely on the findings of preoperative imaging(e.g.,Computed tomography or Magnetic resonance imaging).In this study,we reviewed four cases of pancreatic LECs to investigate the feature of LECs.We reviewed these cases with regard to symptoms,imaging findings,surgical procedures,and other clinical factors.We found that LEC was associated with unique characteristics on imaging findings.A preoperative diagnosisof LEC may be possible by comprehensively evaluating its clinical and imaging findings. 展开更多
关键词 Lymphoepithelial cyst Preoperative diagno-sis Magnetic resonance imaging
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A case report of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct 被引量:2
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作者 Mitsuyoshi Okazaki Isamu Makino +7 位作者 Hirohisa Kitagawa Shinichi Nakanuma Hironori Hayashi Hisatoshi Nakagawara Tomoharu Miyashita Hidehiro Tajima Hiroyuki Takamura tetsuo ohta 《World Journal of Gastroenterology》 SCIE CAS 2014年第3期852-856,共5页
We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct.A 76-year-old male was referred to our hospital for treatment of a pancreatic tumo... We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct.A 76-year-old male was referred to our hospital for treatment of a pancreatic tumor.Preoperative examinations revealed a poorly defined tumor in the main pancreatic duct in the body of the pancreas,accompanied with severe dilatation of the main pancreatic duct,which was diagnosed as an intraductal papillary-mucinous neoplasm.We performed distal pancreatectomy and splenectomy.The pathological examination revealed that the tumor consisted of a mixture of anaplastic carcinoma(giant cell type)and adenocarcinoma in the pancreas.There was a papillary projecting tumor composed of anaplastic carcinoma in the dilated main pancreatic duct.The patient is now receiving chemotherapy because liver metastasis was detected 12 mo after surgery.In this case,we could observe a remarkable intraductal tumor growth into the main pancreatic duct.We also discuss the pathogenesis and characteristics of this rare tumor with specific tumor growth. 展开更多
关键词 Anaplastic carcinoma Giant cell carcinoma Intraductal tumor growth Papillary projecting tumor
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Surgical anatomy of the innervation of pylorus in human and Suncus murinus, in relation to surgical technique for pylorus-preserving pancreaticoduodenectomy 被引量:1
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作者 Shuang-Qin Yi Fei Ru +8 位作者 tetsuo ohta Hayato Terayama Munekazu Naito Shogo Hayashi Sichen Buhe Nozomi Yi Takayoshi Miyaki Shigenori Tanaka Masahiro Itoh 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第14期2209-2216,共8页
AIM: To clarify the innervation of the antro-pyloric region in humans from a clinico-anatomical perspective. METHODS: The stomach, duodenum and surrounding structures were dissected in 10 cadavers, and immersed in a... AIM: To clarify the innervation of the antro-pyloric region in humans from a clinico-anatomical perspective. METHODS: The stomach, duodenum and surrounding structures were dissected in 10 cadavers, and immersed in a 10mg/L solution of alizarin red S in ethanol to stain the peripheral nerves. The distribution details were studied to confirm innervations in the above areas using a binocular microscope. Similarly, innervations in 10 Suncus murinus were examined using the method of whole-mount imm unohistochemistry. RESULTS: The innervation of the pyloric region in humans involved three routes: One arose from the anterior hepatic plexus via the route of the suprapyloric/supraduodenal branch of the right gastric artery; the second arose from the anterior and posterior gastric divisions, and the third originated from the posterior-lower region of the pyloric region, which passed via the infrapyloric artery or retroduodenal branches and was related to the gastroduodenal artery and right gastroepiploic artery. For Suncus murinus, results similar to those in humans were observed. CONCLUSION: There are three routes of innervation of the pyloric region in humans, wherein the route of the right gastric artery is most important for preserving pyloric region innervation. Function will be preserved by more than 80% by preserving the artery in pylorus-preserving pancreaticoduodenectomy (PPPD). However, the route of the infrapyloric artery should not be disregarded. This route is related to several arteries (the right gastroepiploic and gastroduodenal arteries), and the preserving of these arteries is advantageous for preserving pyloric innervation in PPPD. Concurrently, the nerves of Latarjet also play an important role in maintaining innervation of the antro-pyloric region in PPPD. This is why pyloric function is not damaged in some patients when the right gastric artery is dissected or damaged in PPPD. 展开更多
关键词 INNERVATION Quality of life Pylorus-preserving pancreaticoduodenectomy Suncus murinus Whole mount immunohistochemistry
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Three-Component Coupling Catalyzed by Phosphine: Preparation of α-Amino γ-Oxo Acid Derivatives 被引量:1
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作者 Yohei Oe Takeshi Inoue +3 位作者 Hiroaki Kishimoto Mitsuhiro Sasaki tetsuo ohta Isao Furukawa 《International Journal of Organic Chemistry》 2012年第2期111-116,共6页
The three-component coupling reaction of ethyl propiolate (1), phthalimide (2), and aldehyde (3) catalyzed by tripheny- lphosphine, was developed. A solution of an equivalent amount of 1 and 2 in benzaldehyde (3a) in ... The three-component coupling reaction of ethyl propiolate (1), phthalimide (2), and aldehyde (3) catalyzed by tripheny- lphosphine, was developed. A solution of an equivalent amount of 1 and 2 in benzaldehyde (3a) in the presence of 30 mol% of PPh3 was heated at 100?C for 48 h to give N-(1-ethoxycarbonyl-3-oxo-3-phenylpropyl)phthalimide (4a) in 83% yield. This reaction was thought to proceed via vinylphosphonium salt formed from the reaction of ethyl propiolate (1) with triphenylphosphine in situ. 展开更多
关键词 THREE-COMPONENT Coupling PHOSPHINE 2-Amino-4-Oxocarboxylic ACID
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An Efficient Synthesis of 2,3-Diaminoacid Derivatives Using Phosphine Catalyst
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作者 Yohei Oe Hiroaki Kishimoto +4 位作者 Nahoko Sugioka Daisuke Harada Yukio Sato tetsuo ohta Isao Furukawa 《International Journal of Organic Chemistry》 2014年第3期189-194,共6页
Ethyl 2,3-diphthalimidoylpropanoate was effectively synthesized from ethyl propynoate with two equivalents of phthalimide catalyzed by triphenylphosphine in good yield. The choice of reaction media was important for s... Ethyl 2,3-diphthalimidoylpropanoate was effectively synthesized from ethyl propynoate with two equivalents of phthalimide catalyzed by triphenylphosphine in good yield. The choice of reaction media was important for selective synthesis of the desired 2,3-diaminocarboxylic acid derivatives. The reaction is considered to occur through a zwitterionic intermediate derived from the reaction of the α,β-unsaturated ester with triphenylphosphine. 展开更多
关键词 Addition ALKYNES AMINO ACIDS Catalysis MULTI-COMPONENT Reaction
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