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Transmembrane serine protease 4 expression in the prognosis of radical resection for biliary tract cancer

World Journal of Gastrointestinal Surgery 2024年第8期16卷 2555-2564页

作者： Yoshiyuki Shibata Takeshi Sudo Sho Tazuma Naoki Tanimine Takashi Onoe Yosuke Shimizu Atsushi Yamaguchi Kazuya Kuraoka Shinya Takahashi hirotaka tashiro Department of Surgery National Hospital Organization Kure Medical Center and Chugoku Cancer CenterHiroshima 737-0023Japan Department of Gastroenterology National Hospital Organization Kure Medical Center and Chugoku Cancer CenterHiroshima 737-0023Japan Department of Diagnostic Pathology National Hospital Organization Kure Medical Centerand Chugoku Cancer CenterHiroshima 737-0023Japan Department of Surgery Graduate School of Biochemical and Health ScienceHiroshima UniversityHiroshima 734-8551Japan

BACKGROUND Recent advancements in biliary tract cancer(BTC)treatment have expanded beyond surgery to include adjuvant therapy,yet the prognosis remains *** prognostic biomarkers could enhance the assessment of patients who have undergone radical resection for *** To determine transmembrane serine protease 4(TMPRSS4)utility as a prognostic biomarker of radical resection for *** Medical records of patients who underwent radical resection for BTC,excluding intrahepatic cholangiocarcinoma,were retrospectively *** associations between TMPRSS4 expression and clinicopathological factors,overall survival,and recurrence-free survival were *** Among the 85 patients undergoing radical resection for BTC,46(54%)were *** TMPRSS4-positive group exhibited significantly higher preoperative carbohydrate antigen 19-9(CA19-9)values and greater lymphatic invasion than the TMPRSS4-negative group(P=0.019 and 0.039,respectively).Postoperative overall survival and recurrence-free survival were significantly worse in the TMPRSS4-positive group(median survival time:25.3 months vs not reached,P<0.001;median survival time:28.7 months vs not reached,P=0.043,respectively).Multivariate overall survival analysis indicated TMPRSS4 positivity,pT3/T4,and resection status R1 were independently associated with poor prognosis(P=0.032,0.035 and 0.030,respectively).TMPRSS4 positivity correlated with preoperative CA19-9 values≥37 U/mL and pathological tumor size≥30 mm(P=0.016 and 0.038,respectively).CONCLUSION TMPRSS4 is a potential prognostic biomarker of radical resection for BTC.

关键词： Biliary tract cancer Biomarker Prognosis Radical resection Transmembrane serine protease 4

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possible role of soluble fibrin monomer complex after gastroenterological surgery

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World Journal of Gastroenterology 2017年第12期23卷 2209-2216页

作者： Masatoshi Kochi Manabu Shimomura Takao Hinoi Hiroyuki Egi Kazuaki Tanabe Yasuyo Ishizaki Tomohiro Adachi hirotaka tashiro Hideki Ohdan Department of Gastroenterological and Transplant Surgery Applied Life SciencesInstitute of Biomedical and Health SciencesHiroshima University Department of Surgery National Hospital Organization Higashihiroshima Medical Center Department of Surgery Institute for Clinical ResearchNational Hospital Organization Kure Medical Center and Chu-goku Cancer Center Department of Surgery National Hospital Organization Hiroshima-nishi Medical Center

AIM To examine the role of soluble fibrin monomer complex(SFMC) in the prediction of hypercoagulable state after gastroenterological *** We collected data on the clinical risk factors and fibrin-related makers from patients who underwent gastroenterological surgery at Hiroshima University Hospital between April 1, 2014 and March 31, 2015. We investigated the clinical significance of SFMC, which is known to reflect the early plasmatic activation of coagulation, in the view of these fibrin related *** A total of 123 patients were included in the present study. There were no patients with symptomatic VTE. Thirty-five(28%) patients received postoperative anticoagulant therapy. In the multivariate analysis, a high SFMC level on POD 1 was independently associated with D-dimer elevation on POD 7(OR = 4.31, 95%CI: 1.10-18.30, P = 0.03). The cutoff SFMC level was 3.8 μg/ml(AUC = 0.78, sensitivity, 63%, specificity, 89%). The D-dimer level on POD 7 was significantly reduced in high-SFMC patients who received anticoagulant therapy in comparison to highSFMC patients who did *** The SFMC on POD 1 strongly predicted the hypercoagulable state after gastroenterological surgery than the clinical risk factors and the other fibrin related markers.

关键词： Hypercoagulable state Gastroenterological surgery Soluble fibrin monomer complex Venous thromboembolism Anticoagulant therapy

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Hepatocellular carcinoma and focal nodular hyperplasia of the liver in a glycogen storage disease patient

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World Journal of Hepatology 2012年第6期4卷 191-195页

作者： Yoshihiro Mikuriya Akihiko Oshita hirotaka tashiro Hironobu Amano Tsuyoshi Kobayashi Kouji Arihiro Hideki Ohdan Division of Frontier Medical Science Department of Surgery Graduate School of Biomedical Sciences Hiroshima University 1-2-3 Kasumi Minami-ku Hiroshima 734-8551 Japan Department of Pathology Hiroshima University Hospital1-2-3 Kasumi Minami-ku Hiroshima 734-8551 Japan

Glycogen storage disease type Ia (GSD-Ia; also called von Gierke disease) is an autosomal recessive disorder of carbohydrate metabolism caused by glucose-6-phosphatase deficiency. There have been many reports describing hepatic tumors in GSD patients; however, most of these reports were of hepatocellular adenomas, whereas there are only few reports describing focal nodular hyperplasia (FNH) or hepatocellular carcinoma (HCC). We report a case with GSD-Ia who had undergone a partial resection of the liver for FNH at 18 years of age and in whom moderately differentiated HCC had developed. Preoperative imaging studies, including ultrasonography, dynamic computer tomography (CT) and magnetic resonance imaging, revealed benign and malignant features. In particular, fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed the atypical findings that FDG accumulated at high levels in the non-tumorous hepatic parenchyma and low levels in the tumor. Right hemihepatectomy was performed. During the perioperative period, high-dose glucose and sodium bicarbonate were administered to control metabolic acidosis. He had multiple recurrences of HCC at 10 mo after surgery and was followed-up with transcatheter arterial chemoembolization. The tumor was already highly advanced when it was found by chance; therefore, a careful follow-up should be mandatory for GSD-I patients as they are at a high risk for HCC, similar to hepatitis patients.

关键词： Glycogen storage disease type Ia Hepato-cellular carcinoma Focal nodular hyperplasia Hepatectomy Metachronous

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Cisplatin-induced activation of TGF-βsignaling contributes to drug resistance

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Oncology Research 2024年第1期32卷 139-150页

作者： SAYAKA IMATSUJI YUKIKO UJIE HIROYUKI ODAKE MASAYA IMOTO SUSUMU ITOH ETSU tashiro Department of Biosciences and Informatics Faculty of Science and TechnologyKeio UniversityYokohama223-8522Japan Department of Neurology Juntendo University Graduate School of MedicineTokyo113-8421Japan Laboratory of Biochemistry Showa Pharmaceutical UniversityTokyo194-8543Japan

Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer ***,the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains *** address this issue,we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell *** these clones,the epithelial marker E-cadherin was downregulated,whereas the mesenchymal marker N-cadherin was ***,the expression of EMT-related transcription factors,including Slug,was *** the other hand,the upregulation of other mesenchymal marker Vimentin was weak,suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant *** mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-β(TGF-β)receptor kinase inhibitors,indicating that TGF-βsignaling is involved in cisplatin-induced the mesenchymallike phenotypic ***,cisplatin was observed to enhance the secretion of TGF-βinto the culture media without influencing TGF-βgene *** results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-βsecretion,ultimately resulting in drug resistance.

关键词： Cisplatin EMT Chemo-resistance TGF-β

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STRUCTURAL PHASE TRANSITION OF ALIPHATIC NYLONS VIEWED FROM THE WAXD/SAXS AND VIBRATIONAL SPECTRAL MEASUREMENTS AND MOLECULAR DYNAMICS CALCULATION

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Chinese Journal of Polymer Science 2007年第1期25卷 73-82页

作者： Kohji tashiro Department of Future Industry-Oriented Basic Science and Materials Toyota Technological InstituteTempakuNagoya 468-8511Japan

The crystalline phase transition of aliphatic nylon 10/10 has been investigated on the basis of the simultaneous measurement of wide-angle and small-angle X-ray scatterings, the infrared spectral measurement and the molecular dynamics calculation. An interpretation of infrared spectra taken for a series of nylon samples and the corresponding model compounds was successfully made, allowing us to assign the infrared bands of the planar-zigzag methylene segments reasonably. As a result the methylene segmental parts of molecular chains were found to experience an order-to-disorder transition in the Brill transition region, where the intermolecular hydrogen bonds are kept alive although the bond strength becomes weaker at higher temperature. The small-angle X-ray scattering data revealed a slight change in lamellar stacking mode in the transition region. The crystal structure has been found to change more remarkably in the temperature region immediately below the melting point, where the conformationally disordered chains experienced drastic rotational and translational motions without any constraints by hydrogen bonds, and the lamellar thickness increased largely along the chain axis. These experimental results were reasonably reproduced by the molecular dynamics calculation performed at the various temperatures.

关键词： Aliphatic nylon Phase transition Wide-angle X-ray diffraction Small-angle X-ray scattering Computer simulation.

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Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2/Bax and activating caspase-3/ICAD pathway

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Acta Pharmacologica Sinica 2004年第05期25卷 149-156页

作者： Shin-ichi tashiro,Satoshi ONODERA,Takashi IKEJIMA Department of Clinical and Biomedical Sciences Showa College of Pharmaceutical Sciences Tokyo 194-8543 Japan Department of Clinical and Biomedical Sciences Showa College of Pharmaceutical Sciences Tokyo 194-8543 Japan China-Japan Research Institute of Medical and Pharmaceutical Sciences Shenyang Pharmaceutical University Shenyang 110016 China prof

AIM: To study the mechanisms by which oridonin inhibited HeLa cell growth in vitro. METHODS: Viability oforidonin-induced HeLa cells was measured by MTT assay. Apoptotic cells with condensed nuclei were visualizedby phase contrast microscopy. Nucleosomal DNA fragmentation was assayed by agarose gel *** activity was assayed using fluorometric protease assay. ICAD, Bcl-2, and Bax proteins expression weredetected by Western blot analysis. RESULTS: Oridonin induced oligonucleosomal fragmentation of DNA andincreased caspase-3 activity, on the other hand, reduced the expression of inhibitor of caspase-3-activated DNase(ICAD), a caspase-3 substrate, at 12 h in HeLa cells. Oridonin-induced DNA fragmentation, caspase-3 activationand down-regulation of ICAD expression were effectively inhibited by a caspase-3 inhibitor, z-DEVD-fmk (z-Asp-Glu-Val-Asp-fmk). However, pretreatment with an inhibitor of poly (ADP-ribose) polymerase (PARP), 3, 4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), did not suppress oridonin-induced HeLa cell death. Inaddition, oridonin-induced apoptosis was associated with an increase in the expression of the apoptosis inducerBax, and a significant reduction in expression of the apoptosis suppressor Bcl-2 in mitochondria. CONCLUSION:Oridonin induces HeLa cells apoptosis by altering balance of Bcl-2 and Bax protein expression and activation ofcaspase-3/ICAD pathway.

关键词： oridonin HeLa cells apoptosis caspase 3 caspases bcl-2 genes bax genes Western blotting

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Investigation of the factors affecting the limit of detection of laser-induced breakdown spectroscopy for surface inspection

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Plasma Science and Technology 2019年第3期21卷 174-181页

作者： Tadatake SATO Kenichi tashiro Yoshizo KAWAGUCHI Hideki OHMURA Haruhisa AKIYAMA Electronics and Photonics Research Institute National Institute of Advanced Science and Technology (AIST) Research Institute for Sustainable Chemistry National Institute of Advanced Science and Technology (AIST)

Laser-induced breakdown spectroscopy(LIBS) was examined to detect a trace substance adhered onto Al alloys for the surface inspection of materials to be adhesively bonded. As an example of Si contamination, silicone oil was employed and sprayed onto substrates with a controlled surface concentration. LIBS measurements employing nanosecond UV pulses(λ?=?266 nm) and an off-axis emission collection system with different detecting heights were performed. Because surface contaminants are involved in the plasma formed by laser ablation of the substrates, the relative contribution of the surface contaminants and the substrates to the plasma emission could be changed depending on the conditions for plasma formation. The limit of detection(LOD) was evaluated under several detecting conditions for investigating the factors that affected the LOD. A significant factor was the standard deviation values of signal intensities obtained for the clean substrates. This value varied depending on the measurement *** the Al alloy(A6061), the smallest LOD obtained was 0.529 μg?·?cm^(-2). Furthermore, an improved LOD(0.299 μg?·?cm^(-2)) was obtained for the Al alloy with a lower Si content.

关键词： laser-induced breakdown spectroscopy adhesive bonding surface contamination detection pre-bond surface inspection

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Diosgenin induces apoptosis in HeLa cells via activation of caspase pathway

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Acta Pharmacologica Sinica 2004年第8期 103-108页

作者： Shin-ichi tashiro,Satoshi ONODERA,Takashi IKEJIMA China Department of Clinical and Biomedical Sciences Department of Clinical and Biomedical Sciences China-Japan Research Institute of Medical and Pharmaceutical Sciences Showa Pharmaceutical University Tokyo 194-8543 Japan Showa Pharmaceutical University Tokyo 194-8543 Japan Shenyang Pharmaceutical University

AIM: To investigate the mechanism of diosgenin-induced HeLa cell apoptosis. METHODS: HeLa cell growth was measured by MTT method. Apoptosis was detected by electron microscopy and agarose gel electrophoresis. Ratio of apoptotic cells was measured by APO-BRDU kit. Cell cycle distribution and changes of mitochondrial membrane potential were monitored by flow cytometry. Caspase activities were assayed by caspase apoptosis detection kit. Western blot analysis was used to evaluate the level of mitochondrial Bcl-2 expression. RESULTS: Diosgenin inhibited HeLa cell growth. HeLa cells treated with diosgenin showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. Caspase family inhibitor (z-VAD-fmk), caspase-9 inhibitor (Ac-AAVALPAVLLALLAPLEHD-CHO), and caspase-3 inhibitor (z-DEVD-fmk) partially prevented diosgenin-induced apoptosis, but not caspase-8 inhibitor (z-IETD-fmk) and caspase-10 inhibitor (z-AEVD-fmk). Diosgenin caused reduction of mitochondrial membrane po

关键词： diosgenin apoptosis caspases mitochondria HeLa cells

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Norcantharidin induces apoptosis in HeLa cells through caspase, MAPK, and mitochondrial pathways

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Acta Pharmacologica Sinica 2004年第11期 118-124页

作者： Shin-ichi tashiro,Satoshi ONODERA,Takashi IKEJIMA Department of Pharmacology Department of Pharmacology Department of Clinical and Biomedical Sciences Shenyang Pharmaceutical University Shenyang 110016 China Shenyang Pharmaceutical University Shenyang 110016 China Showa Pharmaceutical University Tokyo 19-8543 Japan

AIM: To investigate the mechanism of norcantharidin (NCTD)-induced HeLa cell apoptosis. METHODS: HeLa cell growth inhibition was measured by MTT method. Apoptosis was detected by Hoechst 33258 staining and agarose gel electrophoresis. Caspase activities were assayed using caspase apoptosis detection kit. Western blot analysis was used to evaluate the level of ICAD, ERK/p-ERK, JNK/p-JNK, and Bcl-XL/Bax expression. RESULTS: Norcantharidin inhibited HeLa cell growth in a time- and dose-dependent manner. HeLa cells treated with norcantharidin showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. Caspase family inhibitor (z-VAD-fmk), caspase-8, -9 inhibitor (z-IETD-fmk, Ac-LEHD-CHO, respectively) and caspase-3 inhibitor (z-DEVD-fmk) partially prevent norcantharidin-induced apoptosis, but initiator caspase-1 inhibitor (Ac-YVAD-fmk) did not. The activities of caspase-3, -8, and -9 were up-regulated after norcantharidin treatment. Furthermore, NCTD-induced activat

关键词： norcantharidin HeLa cells apoptosis caspases Bcl-2 family MAP kinase signaling system

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Evodiamine induces tumor cell death through different pathways: apoptosis and necrosis

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Acta Pharmacologica Sinica 2004年第1期 85-91页

作者： Shin-ichi tashiro,Satoshi ONODERA,Takashi IKEJIMA Department of Clinical and Biomedical Sciences Showa Pharmaceutical University Tokyo 194-8543 Japan Department of Clinical and Biomedical Sciences Showa Pharmaceutical University Tokyo 194-8543 Japan China-Japan Research Institute of Medical and Pharmaceutical Sciences Department of Clinical and Biomedical Sciences Showa Pharmaceutical University Tokyo 194-8543 Japan

AIM: To study the different death pathways in human cervical cancer HeLa and melanoma A375-S2 cells Initiated by evodiamine. METHODS: Viability of evodiamine-induced HeLa and A375-S2 cells was measured by MTT assay. Apoptotic cells with condensed or fragmented nuclei were visualized by Hoechst 33258 staining. Nucleoso mal DNA fragmentation was assayed by agarose gel electrophoresis. Proportion of cell death through apoptotic and necrotic pathways was determined by LDH activity-based cytotoxicity assays. Cell cycle distribution was observed by flow cytometry. RESULTS: Evodiamine induced HeLa and A375-S2 cell death dose- and time-dependently. Caspase-3 and -8 were activated in apoptosis induced by evodiamine 15μmol/L. However, over 24- h

关键词： evodiamine apoptosis necrosis caspases MAP kinase signaling system

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