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Factors predicting upstaging from clinical N0 to pN2a/N3a in breast cancer patients

World Journal of Clinical Oncology 2022年第9期13卷 748-757页

作者： Goshi Oda Tsuyoshi Nakagawa Hiroki Mori Iichiro Onishi Tomoyuki Fujioka Mio Mori kazunori kubota Ryoichi Hanazawa Akihiro Hirakawa Toshiaki Ishikawa Kentaro Okamoto Hiroyuki Uetakesszsz Department of Breast Surgery Tokyo Medical and Dental UniversityTokyo 1138519Japan Department of Plastic and Reconstructive Surgery Tokyo Medical and Dental UniversityTokyo 1138519Japan Department of Pathology Tokyo Medical and Dental UniversityTokyo 1138519Japan Department of Radiology Tokyo Medical and Dental UniversityTokyo 1138519Japan Department of Clinical Biostatistics Tokyo Medical and Dental UniversityTokyo 1138519Japan Department of Specialized Surgeries Tokyo Medical and Dental UniversityTokyo 1138519Japan

BACKGROUND With sentinel node metastasis in breast cancer(BC)patients,axillary lymph node(ALN)dissection is often omitted from cases with breast-conserving surgery.Omission of lymph node dissection reduces the invasiveness of surgery to the patient,but it also obscures the number of metastases to non-sentinel nodes.The possibility of finding≥4 lymph nodes(pN2a/pN3a)preoperatively is important given the ramifications for postoperative treatment.AIM To search for clinicopathological factors that predicts upstaging from N0 to pN2a/pN3a.METHODS Patients who were sentinel lymph node(SLN)-positive and underwent ALN dissection between September 2007 and August 2018 were selected by retrospective chart review.All patients had BC diagnosed preoperatively as N0 with axillary evaluation by fluorodeoxyglucose(FDG) positron emission tomography/computed tomography and ultrasound (US)examination. When suspicious FDG accumulation was found in ALN, the presence of metastasiswas reevaluated by second US. We examined predictors of upstaging from N0 to pN2a/pN3a.RESULTSAmong 135 patients, we identified 1-3 ALNs (pN1) in 113 patients and ³4 ALNs (pN2a/pN3a) in22 patients. Multivariate analysis identified the total number of SLN metastasis, the maximaldiameter of metastasis in the SLN (SLNDmax), and FDG accumulation of ALN as predictors ofupstaging to pN2a/pN3a.CONCLUSIONWe identified factors involved in upstaging from N0 to pN2a/pN3a. The SLNDmax and numberof SLN metastasis are predictors of ≥ 4 ALNs (pN2a/pN3a) and predictors of metastasis to nonsentinelnodes, which have been reported in the past. Attention should be given to axillaryaccumulations of FDG, even when faint.

关键词： Breast cancer Axillary lymph node metastasis Positron emission tomography/computed tomography Sentinel lymph node Predictive factors of lymphnode metastasis Standardized uptake value max Diameter of sentinel lyphonode metastasis

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Tumor characteristics of ductal carcinoma in situ of breast visualized on [F-18] fluorodeoxyglucose-positron emission tomography/computed tomography: Results from a retrospective study

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World Journal of Radiology 2016年第8期8卷 743-749页

作者： Tomoyuki Fujioka kazunori kubota Akira Toriihara Youichi Machida Kaori Okazawa Tsuyoshi Nakagawa Yukihisa Saida Ukihide Tateishi Department of Diagnostic Radiology Tokyo Medical and Dental University Department of Radiology Kameda Kyobashi Clinic Department of Breast Surgery Tokyo Medical and Dental University

AIM To clarify clinicopathological features of ductal carcinoma in situ(DCIS) visualized on [F-18] fluorodeoxyglucosepositron emission tomography/computed tomography(FDG-PET/CT).METHODS This study retrospectively reviewed 52 consecutive tumors in 50 patients with pathologically proven pure DCIS who underwent [F-18] FDG-PET/CT before surgery. [F-18] FDG-PET/CT was performed after biopsy in all patients. The mean interval from biopsy to [F-18] FDGPET/CT was 29.2 d. [F-18] FDG uptake by visual analysis and maximum standardized uptake value(SUVmax) was compared with clinicopathological characteristics.RESULTS[F-18] FDG uptake was visualized in 28 lesions(53.8%) and the mean and standard deviation of SUVmax was 1.63 and 0.90. On univariate analysis, visual analysis and the SUVmax were associated with symptomatic presentation(P = 0.012 and 0.002, respectively), palpability(P = 0.030 and 0.024, respectively), use of core-needle biopsy(CNB)(P = 0.023 and 0.012, respectively), ultrasound-guided biopsy(P = 0.040 and 0.006, respectively), enhancing lesion ≥ 20 mm on magnetic resonance imaging(MRI)(P = 0.001 and 0.010, respectively), tumor size ≥ 20 mm on histopathology(P = 0.002 and 0.008, respectively). However, [F-18] FDG uptake parameters were not significantly associated with age, presence of calcification on mammography, mass formation on MRI, presence of comedo necrosis, hormone status(estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2), and nuclear grade. The factors significantly associated with visual analysis and SUVmax were symptomatic presentation(P = 0.019 and 0.001, respectively), use of CNB(P = 0.001 and 0.031, respectively), and enhancing lesion ≥ 20 mm on MRI(P = 0.001 and 0.049, respectively) on multivariate analysis.CONCLUSION Although DCIS of breast is generally non-avid tumor, symptomatic and large tumors(≥ 20 mm) tend to be visualized on [F-18] FDG-PET/CT.

关键词： Ductal carcinoma in situ Positron emission tomography Breast cancer [F-18] fluorodeoxyglucosepositron emission tomography/computed tomography

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Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 557-562页

作者： Toshiaki Tsurui Yuya Hirasawa Yutaro kubota Kiyoshi Yoshimura Takuya Tsunoda Department of Medical Oncology Showa UniversityTokyo 1428555Japan Department of Clinical Immuno Oncology Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyo 1578577Japan

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic involvement.Moreover,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently unavailable.CASE SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe jaundice.Computed tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated adenocarcinoma.No RAS or BRAF mutations were detected.The Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was 2.Biliary drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly initiated.Subsequently,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse events.CONCLUSION Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

关键词： Colorectal neoplasms Panitumumab Chemotherapy Hyperbilirubinemia Jaundice Case report

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EB病毒相关淋巴肿瘤的发病机制及FDG PET/CT显像

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中华核医学与分子影像杂志 2018年第2期38卷 150-150页

作者：唐军 Akira Toriihara Reiko Nakajima Ayako Arai Masashi Nakadate Koichiro Abe kazunori kubota Ukihide Tateishi 上海交通大学医学院附属苏州九龙医院核医学科 Department of Diagnostic Radiology and Nuclear Medicine Tokyo Medical and Dental University

EB病毒（EBV）是最常见的病毒之一,在世界范围内有超过90%的成人会感染EBV。一些淋巴肿瘤的基因组已被探明,其组织病理亚型有多种,病史和病程也多变。许多与免疫功能不全相关的B细胞淋巴增殖性疾病都与EBV感染有关。随着器官移植和免疫... 详细信息

EB病毒（EBV）是最常见的病毒之一,在世界范围内有超过90%的成人会感染EBV。一些淋巴肿瘤的基因组已被探明,其组织病理亚型有多种,病史和病程也多变。许多与免疫功能不全相关的B细胞淋巴增殖性疾病都与EBV感染有关。随着器官移植和免疫抑制药物使用的日趋普遍,这些疾病的发病率也越来越高。而且,一些免疫功能正常的人也会患EBV阳性的淋巴瘤。利用;F-脱氧葡萄糖（FDG）PET/CT评价不明原因的全身淋巴结病变患者,其中部分患者应考虑有淋巴肿瘤的可能,需仔细分析其病史和病程。该文描述了EBV相关淋巴肿瘤的发病机制,展示了部分典型病例的;F-FDG PET/CT显像结果,并综述了其他EBV相关疾病（如感染性单核细胞增多症和鼻咽癌）。

关键词： EB病毒 FDG PET/CT 淋巴增殖性疾病淋巴瘤

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MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1

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Oncology Research 2024年第3期32卷 463-476页

作者： Hur SUN MASANORI KAWANO TATSUYA IWASAKI ICHRO ITONAGA YUTA kubota HROSHI TSUMURA KAZUHRO TANAKA Department of Orthopaedic Surgery Faculty of MedicineOita UniversityOita879-5503Japan

An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.

关键词： MiR-329-3p TCF7L1 Wnt/β-catenin pathway Osteosarcoma Proliferation

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Low temperature-mediated repression and far-red light-mediated induction determine morning FLOWERING LOCUS T expression levels

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Journal of Integrative Plant Biology 2024年第1期66卷 103-120页

作者： Hayeon Kim Hye Won Kang Dae Yeon Hwang Nayoung Lee Akane kubota Takato Imaizumi Young Hun Song Department of Agricultural Biotechnology Seoul National UniversitySeoul 08826Korea Department of Biology Ajou UniversitySuwon 16499Korea Plant Genomics and Breeding Institute Seoul National UniversitySeoul 08826Korea Graduate School of Science and Technology Nara Institute of Science and TechnologyIkomaNara 630‐0192Japan Department of Biology University of WashingtonSeattleWA 98195USA Institute of Agricultural Life Sciences Seoul National UniversitySeoul 08826Korea

In order to flower in the appropriate season,plants monitor light and temperature changes and alter downstream pathways that regulate florigen genes such as Arabidopsis(Arabidopsis thaliana)FLOWERING LOCUS T(FT).In Arabidopsis,FT messenger RNA levels peak in the morning and evening under natural long-day conditions(LDs).However,the regulatory mechanisms governing morning FT induction remain poorly understood.The morning FT peak is absent in typical laboratory LDs characterized by high red:far-red light(R:FR)ratios and constant temperatures.Here,we demonstrate that ZEITLUPE(ZTL)interacts with the FT repressors TARGET OF EATs(TOEs),thereby repressing morning FT expression in natural environments.Under LDs with simulated sunlight(R:FR=1.0)and daily temperature cycles,which are natural LD-mimicking environmental conditions,FT transcript levels in the ztl mutant were high specifically in the morning,a pattern that was mirrored in the toe1 toe2 double mutant.Low night-to-morning temperatures increased the inhibitory effect of ZTL on morning FT expression by increasing ZTL protein levels early in the morning.Far-red light counteracted ZTL activity by decreasing its abundance(possibly via phytochrome A(phyA))while increasing GIGANTEA(GI)levels and negatively affecting the formation of the ZTL-GI complex in the morning.Therefore,the phyA-mediated high-irradiance response and GI play pivotal roles in morning FT induction.Our findings suggest that the delicate balance between low temperature-mediated ZTL activity and the far-red light-mediated functions of phyA and GI offers plants flexibility in fine-tuning their flowering time by controlling FT expression in the morning.

关键词： far-red light FLOWERING LOCUS T flowering time GIGANTEA low night-to-morning temperature natural long days phytochrome A red to far-red ratio ZEITLUPE

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Challenges of Bioethics Education in Pediatric Basic Nursing Education: A Faculty Perspective

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Health 2024年第2期16卷 105-117页

作者： Junko Nemoto Chikage kubota Yukiko Yoshikawa Faculty of Nursing Hyogo University Kakogawa Japan Department of Emergency Medical Science Suzuka University of Medical Science Suzuka Japan

In the field of pediatric nursing, in the perinatal period, numerous ethical issues arise alongside the advancement of medical technology. However, sufficient education on bioethics is not provided in the pediatric nursing domain of basic nursing education. The purpose of this research is to examine the current status of bioethics education in the pediatric nursing domain of basic nursing education and explore the challenges perceived by the pediatric nursing faculty regarding bioethics education. The research method was a questionnaire survey on 100 randomly selected pediatric nursing faculty members from nursing universities across Japan. The results revealed that although bioethics issues were considered important, the emphasis remained primarily on addressing bioethics as part of nursing that respects children’s rights. Furthermore, respondents expressed difficulties regarding teaching methods and content related to bioethics.

关键词： Basic Nursing Education Bioethics Education Pediatric Nursing

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Microbial characteristics in anaerobic membrane bioreactor treating domestic sewage:Effects of HRT and process performance

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Journal of Environmental Sciences 2022年第1期34卷 392-399页

作者： Jialing Ni Jiayuan Ji Yu-You Li Kengo kubota Department of Civil and Environmental Engineering Graduate School of EngineeringTohoku University6-6-06 AobaAramakiAoba-ku 980-8579SendaiJapan Department of Frontier Science for Advanced Environment Graduate School of Environmental StudiesTohoku University6-6-06 AobaAramakiAoba-ku 980-8579SendaiJapan

Two anaerobic membrane bioreactors(AnMBRs)equipped with different membrane pore size(0.4 or 0.05μm)were operated at 25℃and fed with domestic wastewater.The hydraulic retention time(HRT)of the reactors was shortened.The microbial communities of the two AnMBRs were investigated by 16S rRNA gene amplicon sequencing to see the effects of HRT.The predominant Archaea was an aceticlastic methanogen Methanosaeta.The composition of hydrogenotrophic methanogens changed with the HRTs:the population of Methanobacterium was higher for longer HRTs,whereas the population of unclassified Methanoregulaceae was higher for shorter HRTs.The Anaerolineae,Bacteroidia and Clostridia bacteria were dominant in both of the reactors,with a combined relative abundance of over 55%.The relative abundance of Anaerolineae was proportional to the biogas production performance.The change in the population of hydrogenotrophic methanogens or Anaerolineae can be used as an indicator for process monitoring.The sum of the relative abundance of Anaerolineae and Clostridia fluctuated slightly with changes in the HRT in both AnMBRs when the reactor was stably operated.The co-occurrence analysis revealed the relative abundance of the operational taxonomic units belonging to Anaerolineae and Clostridia was functionally equivalent during the treatment of real domestic sewage.A principal coordination analysis revealed that the changes in the microbial community in each reactor were consistent with the change of HRT.In addition,both the HRT and the stability of the process are important factors for maintaining microbial community structures.

关键词： Anaerobic membrane bioreactor Co-occurrence analysis Hydrogenotrophic methanogen HRT Microbial community structure Principal coordinate analysis

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Three cases of retroperitoneal schwannoma diagnosed by EUS-FNA

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World Journal of Gastroenterology 2011年第29期17卷 3459-3464页

作者： Taiki Kudo Hiroshi Kawakami Masaki Kuwatani Nobuyuki Ehira Hiroaki Yamato kazunori Eto Kanako kubota Masahiro Asaka Department of Gastroenterology Hokkaido University Graduate School of MedicineKita 15Nishi 7Kita-kuSapporo060-8638Japan Department of Surgical pathology Hokkaido University HospitalKita 14Nishi 5Kita-kuSapporo060-8638Japan

Schwannomas are peripheral nerve tumors that are typically solitary and benign.Their diagnosis is largely based on surgically resected specimens.Recently,a number of case reports have indicated that retroperitoneal schwannomas could be diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).We report the diagnosis of three cases of schwannoma using EUS-FNA.Subjects were two males and one female,ages 22,40,and 46 years,respectively,all of whom were symptom-free.Imaging findings showed well-circumscribed round tumors.However,as the tumors could not be diagnosed using these findings alone,EUS-FNA was performed.Hematoxylin-eosin staining of the resulting tissue fragments revealed bland spindle cells with nuclear palisading.There was no disparity in nuclear sizes.Immunostaining revealed S-100 protein positivity and all cases were diagnosed as schwannomas.Ki-67 indexes were 3%-15%,2%-3%,and 3%,respectively.No case showed any signs of malignancy.As most schwannomas are benign tumors and seldom become malignant,we observed these patients without therapy.All tumors demonstrated no enlargement and no change in characteristics.Schwannomas are almost always benign and can be observed following diagnosis by EUS-FNA.

关键词：周围神经诊断腹膜良性肿瘤病例报告免疫染色手术切除外切圆

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The anti-oncogenic effect of 17-DMAG via the inactivation of HSP90 and MET pathway in osteosarcoma cells

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Oncology Research 2023年第5期31卷 631-643页

作者： MASANORI KAWANO KAZUHIRO TANAKA ICHIRO ITONAGA TATSUYA IWASAKI YUTA kubota HIROSHI TSUMURA Department of Orthopaedic Surgery Faculty of MedicineOita UniversityOita879-5593Japan

Heat shock protein(HSP)90 plays a crucial role in correcting the misfolded three-dimensional structure of proteins,assisting them in folding into proper conformations.HSP90 is critical in maintaining the normal functions of various proteins within cells,as essential factors for cellular homeostasis.Contrastingly,HSP90 simultaneously supports the maturation of cancer-related proteins,including mesenchymal epithelial transition factor(MET)within tumor cells.All osteosarcoma cell lines had elevated MET expression in the cDNA array in our possession.MET,a tyrosine kinase receptor,promotes proliferation and an anti-apoptotic state through the activation of the MET pathway constructed by HSP90.In this study,we treated osteosarcoma cells with an HSP90 inhibitor,17-demethoxygeldanamycin hydrochloride(17-DMAG),and assessed the changes in the MET signaling pathway and also the antitumor effect of the drug.The cell cycle in osteosarcoma cells administered 17-DMAG was found to be halted at the G2/M phase.Additionally,treatment with 17-DMAG inhibited cell proliferation and induced apoptosis.Inhibition of tumor cell proliferation was also observed in an in vivo model system,mice that were treated with 17-DMAG.Based on the results of this study,we were able to confirm that 17-DMAG promotes inhibition of osteosarcoma cell proliferation and induction of apoptosis by inhibition of MET,a protein highly expressed in osteosarcoma cells.This approach may be useful for the establishment of a new treatment strategy for patients resistant to the standard treatment for osteosarcoma.

关键词： Osteosarcoma MET HSP90 17-DMAG

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