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Role of RANKL/RANK in primary and secondary breast cancer

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World Journal of Orthopedics 2013年第4期4卷 178-185页

作者： toshiyuki yoneda Soichi Tanaka Kenji Hata Division of Hematology and Oncology Department of Medicine Indiana University School of MedicineIndianapolis IN 46202 United States Department of Biochemistry Osaka University Graduate School of DentistrySuita Osaka 565-0871 Japan

Bone is one of the most preferential metastatic target sites of breast cancer. Bone possesses unique biological microenvironments in which various growth factors are stored and continuously released through osteoclastic bone resorption, providing fertile soil for circulating breast cancer cells. Bone-disseminated breast cancer cells in turn produce osteotropic cytokines which modulate bone environments. Under the influences of breast cancer-produced cytokines, osteoblasts express elevated levels of Ligand for receptor activator of nuclear factor-κB(RANKL) and stimulate osteoclastogenesis via binding to the receptor receptor activator of nuclear factor-κB(RANK) and activating its downstream signaling pathways in hematopoietic osteoclast precursors, which causes further osteoclastic bone destruction. Establishment of crosstalk with bone microenvironments(so called vicious cycle) is an essential event for metastatic breast cancer cells to develop bone metastasis. RANKL and RANK play a central role in this crosstalk. Moreover, recent studies have demonstrated that RANKL and RANK are involved in tumorigenesis and distant metastasis independent of bone microenvironments. Pharmacological disruption of the RANKL/RANK interplay should be an effective therapeutic intervention for primary breast tumors and bone and non-bone metastasis. In this context, denosumab, which is neutralizing monoclonal antibody against RANKL, is a mechanismbased drug for the treatment of bone metastases and would be beneficial for breast cancer patients with bone metastases and potentially visceral organ metastases.

关键词： Bone metastasis Osteoclasts Bone resorption Osteoblasts Stromal cells Epithelial-mesenchymal transition Bone pain

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破骨细胞引起骨吸收的分子调控

中华口腔医学杂志 2009年第Z1期44卷 93-93页

作者： toshiyuki yoneda 1-8Yanmadaoka DepartmentofBiochenmistry Japan Osak871 OsakaUniversityGraduateSchoolofDentistry Suita

Crosstalk between cancer and bone microenvironment in bone metastasis

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中国口腔颌面外科杂志 2008年第B5期6卷 22-22页

作者： toshiyuki yoneda Department of Biochemistry Osaka University Graduate School of Dentistry 1-8 Yamadaoka Suita Osaka 565-0871 Japan

Bone is one of the most preferential target sites for cancers such as breast, prostate and lung cancers to metastasize.

关键词：色度亮度干扰癌症微环境骨转移治疗方法

Significance of oxidative stress and antioxidant capacity tests as biomarkers of premature ovarian insufficiency: A case control study

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World Journal of Clinical Cases 2024年第3期12卷 479-487页

作者： Kaoru Kakinuma toshiyuki Kakinuma Department of Obstetrics and Gynecology International University of Health and Welfare HospitalTochigi 329-2763Japan Graduate School of Medicine International University of Health and WelfareTokyo 107-8402Japan

BACKGROUND Premature ovarian insufficiency(POI)is a condition that causes secondary amenorrhea owing to ovarian hypofunction at an early *** follicular depletion results in intractable infertility,thereby considerably reducing the quality of life of *** the continuum in weakened ovarian function,progressing from incipient ovarian failure(IOF)to transitional ovarian failure and further to POI,it is necessary to develop biomarkers for predicting *** oxidative stress states in IOF and POI were comprehensively evaluated via oxidative stress[diacron-reactive oxygen metabolites(d-ROMs)]test and anti-oxidant capacity[biological antioxidant potential(BAP)].METHODS Females presenting with secondary amenorrhea over 4 mo and a follicle stimulating hormone level of>40 mIU/mL were categorized into the POI *** presenting with a normal menstrual cycle and a follicle stimulating hormone level of>10.2 mIU/mL were categorized into the IOF *** females without ovarian hypofunction were categorized into the control *** females aged<40 years who visited our hospital from January 2021 to June 2022,we recruited 11 patients into both POI and IOF *** the potential antioxidant capacity,the relative oxidative stress index(BAP/d-ROMs×100)was calculated,and the oxidative stress defense system was comprehensively *** d-ROMs were significantly higher in the POI and IOF groups than in the control group,(478.2±58.7 ***,434.5±60.6 ***,and 341.1±35.1 ***,respectively)(*** is equivalent to 0.08 mg/dL of hydrogen peroxide).However,no significant difference was found between the POI and IOF *** BAP,no significant difference was found between the control,IOF,and POI groups(2078.5±157.4μmol/L,2116.2±240.2μmol/L,and 2029.0±186.4μmol/L,respectively).The oxidative stress index was significantly higher in the POI and IOF groups than in the control group(23.7±3.3,20.7±3.6,and 16.5±2.1,respectively).However,no signifi

关键词： Premature ovarian insufficiency Oxidative stress Diacron-reactive oxygen metabolites test Biological antioxidant potential Infertility Biomarker

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer:A systematic review and meta-analysis

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1578-1595页

作者： Eric toshiyuki Nakamura Amanda Park Marina Alessandra Pereira Daniel Kikawa Francisco Tustumi Department of Gastroenterology Instituto do CâncerHospital das Clínicas da Universidade de São PauloFaculdade de MedicinaUniversidade de São PauloSão Paulo 01246000Brazil Department of Scientific Initiation Universidade Mogi das CruzesSão Paulo 08780911Brazil Department of Evidence-Based Medicine Centro Universitário LusíadaCentre for Evidence-Based MedicineCentro Universitário Lusíada(UNILUS)SantosBrazil Department of Surgery Hospital Israelita Albert EinsteinSão Paulo 05652900Brazil

BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many *** prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly *** To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric *** A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and ***,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were ***-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect *** The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 ***40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term ***1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant *** The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

关键词： Heat-shock proteins Heat-shock response Prognosis Esophageal neoplasms Meta-analysis

Abnormal uterine bleeding successfully treated via ultrasoundguided microwave ablation of uterine myoma lesions: Three case reports

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World Journal of Clinical Cases 2024年第5期12卷 980-987页

作者： toshiyuki Kakinuma Kaoru Kakinuma Rora Okamoto Kaoru Yanagida Michitaka Ohwada NobuhiroTakeshima Takeshima Department of Obstetrics and GynecologyInternational University of Health and Welfare HospitalTochigi 329-2763Japan

BACKGROUND Microwave endometrial ablation(MEA)is a minimally invasive treatment method for heavy menstrual ***,additional treatment is often required after recurrence of uterine myomas treated with ***,because this treatment ablates the endometrium,it is not indicated for patients planning to become *** overcome these issues,we devised a method for ultrasound-guided microwave ablation of uterine myoma feeder *** report three patients successfully treated for heavy menstrual bleeding,secondary to uterine myoma,using our novel *** SUMMARY All patients had a favorable postoperative course,were discharged within 4 h,and experienced no ***,no postoperative recurrence of heavy menstrual bleeding was *** method also reduced the myoma’s maximum *** This method does not ablate the endometrium,suggesting its potential appli-cation in patients planning to become pregnant.

关键词： Uterine myoma Microwave Heavy menstrual bleeding Dysmenorrhea Fertility preservation Case report

Elucidating microbial iron corrosion mechanisms with a hydrogenase-deficient strain of Desulfovibrio vulgaris

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mLife 2024年第2期3卷 269-276页

作者： Di Wang toshiyuki Ueki Peiyu Ma Dake Xu Derek R.Lovley Electrobiomaterials Institute Key Laboratory for Anisotropy and Texture of Materials(Ministry of Education)Northeastern UniversityShenyangChina Shenyang National Laboratory for Materials Science Northeastern UniversityShenyangChina Department of Microbiology University of MassachusettsAmherstMAUSA

Sulfate-reducing microorganisms extensively contribute to the corrosion of ferrous metal *** is substantial debate over their corrosion *** investigated Fe^(0) corrosion with Desulfovibrio vulgaris,the sulfate reducer most often employed in corrosion *** were grown with both lactate and Fe^(0) as potential electron donors to replicate the common environmental condition in which organic substrates help fuel the growth of corrosive ***^(0) was corroded in cultures of a *** hydrogenase-deficient mutant with the 1:1 correspondence between Fe^(0) loss and H_(2) accumulation expected for Fe^(0) oxidation coupled to H+reduction to H_(2).This result and the extent of sulfate reduction indicated that *** was not capable of direct Fe^(0)-to-microbe electron transfer even though it was provided with a supplementary energy source in the presence of abundant ferrous *** in the hydrogenase-deficient mutant cultures was greater than in sterile controls,demonstrating that H_(2) removal was not necessary for the enhanced corrosion observed in the presence of *** parental H_(2)-consuming strain corroded more Fe^(0) than the mutant strain,which could be attributed to H_(2) oxidation coupled to sulfate reduction,producing sulfide that further stimulated Fe^(0) *** results suggest that H_(2) consumption is not necessary for microbially enhanced corrosion,but H_(2) oxidation can indirectly promote corrosion by increasing sulfide generation from sulfate *** finding that *** was incapable of direct electron uptake from Fe^(0) reaffirms that direct metal-to-microbe electron transfer has yet to be rigorously described in sulfate-reducing microbes.

关键词： electrobiocorrosion electron transfer hydrogen transfer microbial corrosion sulfate-reducing microbes

Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis

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World Journal of Gastroenterology 2024年第13期30卷 1871-1886页

作者： Kentaro Kojima Kenji Watanabe Mikio Kawai Soichi Yagi Koji Kaku Maiko Ikenouchi toshiyuki Sato Koji Kamikozuru Yoko Yokoyama Tetsuya Takagawa Masahito Shimizu Shinichiro Shinzaki Department of Gastroenterology Hyogo Medical UniversityNishinomiya 663-8501Japan Department of Gastroenterology Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Internal Medicine for Inflammatory Bowel Disease The University of ToyamaToyama 930-0194Japan Center for Clinical Research and Education Hyogo Medical UniversityNishinomiya 663-8501Japan

BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are *** To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical *** We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease *** consecutive UC patients who received TOF between May 2018 and February 2020 were *** were followed up until August *** primary outcome was the clinical response rate at week *** outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week *** The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,*** overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after *** 6 patients with herpes zoster(HZ)developed the infection after achieving remission by *** TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-α*** relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off *** attention is needed for tapering and H

关键词： Ulcerative colitis Tofacitinib Janus kinase inhibitor Real-world Biologics

Uterine artery pseudoaneurysm caused by hysteroscopic surgery: A case report

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World Journal of Clinical Cases 2024年第26期12卷 5968-5973页

作者： Kaoru Kakinuma toshiyuki Kakinuma Kyouhei Ueyama Rora Okamoto Kaoru Yanagida Nobuhiro Takeshima Michitaka Ohwada Department of Obstetrics and Gynecology International University of Health and Welfare Hospital537-3 IguchiNasushiobaraTochigi 329-2763Japan

BACKGROUND We report a case of uterine artery pseudoaneurysm(UAP)occurrence during hysteroscopic endometrial polypectomy and its treatment via uterine artery embolization(UAE).CASE SUMMARY A 48-year-old primigravid,primiparous patient was incidentally found to have an endometrial polyp during a health checkup,and underwent a hysteroscopic polypectomy at another *** cervix was dilated with a Laminken-R®*** the Laminken-R®was withdrawn,a large amount of genital bleeding was *** bleeding persisted after the hysteroscopic polypectomy,and,as hemostasis became impossible,the patient was transferred to our hospital by *** arrival,transvaginal ultrasonography revealed a 3-cm hypoechoic mass with a swirling internal pulse on the right side of the uterus,and color Doppler ultrasonography showed feeder vessels penetrating the *** contrast-enhanced computed tomography(CT)confirmed the presence of a mass at this site,and vascular proliferation was observed within the uterine ***,UAP was diagnosed,and UAE was *** patient’s postoperative course was uneventful,and 6 mo post-UAE,no recurrence of blood flow to the UAP was *** When abnormal genital bleeding occurs during hysteroscopic surgery,ultrasonography and contrast-enhanced CT can assist in the detection of early UAPs.

关键词： Cervical dilation Hysteroscopic surgery Uterine artery pseudoaneurysm Uterine artery embolization Case report