Details of a Researcher - Hayashida, Tetsu

Papers - Hayashida, Tetsu

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増大号全領域をコンプリート!　超進化!AI時代の臨床検査各論 3章　生理学的検査乳房超音波検査

亀山友恵, 林田哲

検査と技術 (株式会社医学書院) 53 ( 8 ) 912 - 915 2025.08

Joint Work, ISSN 03012611

The Future of Breast Cancer Diagnosis in Japan with AI and Ultrasonography

Fujioka Tomoyuki, Tsukada Jitsuro, Hayashida Tetsu, Yamaga Emi, Tsukada Hiroko, Kubota Kazunori, Tateishi Ukihide

JMA Journal (Japan Medical Association / The Japanese Associaiton of Medical Sciences) 8 ( 1 ) 91 - 101 2025.01

Joint Work, ISSN 2433328X

In Japan, mammography is commonly used for breast cancer screening. However, the mortality rate has not decreased, possibly due to the low screening uptake and the high prevalence of dense breast tissue among Japanese women, which reduces mammography's effectiveness. A recent prospective study in Japan, J-START, demonstrated that combining mammography with ultrasonography increases detection rates and reduces the incidence of interval cancers, highlighting the significance of ultrasound examinations.Artificial Intelligence (AI) technologies, particularly in machine learning and deep learning, offer promising solutions to enhance the accuracy and efficiency of breast ultrasound diagnostics. This review explores AI's current capabilities in breast ultrasound imaging, emphasizing key advancements in breast lesion detection and diagnosis. Additionally, we introduce AI-based breast ultrasound diagnostic support programs approved by the Pharmaceuticals and Medical Devices Agency, which include programs for detecting lesion candidate regions and diagnosing the necessity of further examination based on detected lesion candidates. These AI tools are expected to improve diagnostic accuracy and efficiency.While AI holds significant promise, several challenges remain. It is essential for physicians to oversee its use responsibly, as there are concerns regarding patient acceptance and environmental impact. This review underscores the revolutionary potential of AI in breast cancer diagnostics and emphasizes the importance of ongoing research and development to overcome existing limitations.

A genome-wide CRISPR/Cas9 knockout screen identifies SEMA3F gene for resistance to cyclin-dependent kinase 4 and 6 inhibitors in breast cancer

Kawai Y., Nagayama A., Miyao K., Takeuchi M., Yokoe T., Kameyama T., Wang X., Seki T., Takahashi M., Hayashida T., Kitagawa Y.

Breast Cancer 32 ( 1 ) 120 - 131 2025.01

Joint Work, ISSN 13406868

Background: Palbociclib is a cell-cycle targeted small molecule agent used as one of the standards of care in combination with endocrine therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Although several gene alterations such as loss of Rb gene and amplification of p16 gene are known to be conventional resistance mechanisms to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, the comprehensive landscape of resistance is not yet fully elucidated. The purpose of this study is to identify the novel resistant genes to the CDK4/6 inhibitors in HR-positive HER2-negative breast cancer. Methods: The whole genome knockout screen using CRISPR/Cas9 genome editing was conducted in MCF7 to identify resistant genes to palbociclib. The candidate genes for resistance were selected by NGS analysis and GSEA analysis and validated by cell viability assay and mouse xenograft models. Results: We identified eight genes including RET, TIRAP, GNRH1, SEMA3F, SEMA5A, GATA4, NOD1, SSTR1 as candidate genes from the whole genome knockout screen. Among those, knockdown of SEMA3F by siRNA significantly and consistently increased the cell viability in the presence of CDK4/6 inhibitors in vitro and in vivo. Furthermore, the level of p-Rb was maintained in the palbociclib treated SEMA3F-downregulated cells, indicating that the resistance is driven by increased activity of cyclin kinases. Conclusion: Our observation provided the first evidence of SEMA3F as a regulator of sensitivity to CDK4/6 inhibitors in breast cancer. The detailed mechanisms of resistance deserve further functional studies to develop the better strategy to overcome resistance in CDK4/6 inhibitors.

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AI for Imaging Diagnosis in Breast Cancer Screening

Kataoka Masako, Fujioka Tomoyuki, Inoue Kenichi, Hayashida Tetsu, Suzuki Takashi

Nihon Nyugan Kenshin Gakkaishi (Journal of Japan Association of Breast Cancer Screening) (Japan Association of Breast Cancer Screening) 34 ( 1 ) 15 - 21 2025

Joint Work, ISSN 09180729

In breast cancer screening, AI-based computer-aided diagnosis (AI-CAD) software has been introduced into diagnostic imaging, mainly mammography (MG), with the expectation of improving sensitivity or efficiency in reading. Overseas evidence demonstrates that sensitivity and specificity of AI-CAD in diagnosing breast cancer is equivalent to those of human readers. Reducing the work load of screening by replacing one of the readers by AI-CAD has been attempted. On the other hand, pitfalls of AI-CAD include automation bias, and the fluctuation of performance by AI-CAD caused by biased training data. Furthermore, when incorporating AI into actual clinical practice, operational considerations—such as the specific conditions of each facility, feasibility of system implementation and cloud utilization, security measures, and determining who will reference the AI-CAD output and at what stage—must all be taken into account.
In the midst of the transition, it is becoming indispensable to develop guidelines at the academic society level, establish quality assurance systems, and accumulate evidence to verify AI’s usefulness over the mid to long term.

A retrospective multi-center cohort study investigating safety of sentinel lymph node biopsy for axillary staging in clinical T3-4c breast cancer

Kuba S., Sagara Y., Yano H., Maeda S., Sakai T., Kojima Y., Hattori M., Asaga S., Tokunaga E., Shien T., Bando H., Anan K., Iwakuma N., Minami S., Yamaguchi M., Harao M., Oikawa M., Sangai T., Ishitobi M., Nakayama T., Hayashida T., Tada M., Tamaki K., Kutomi G., Tomiguchi M., Harada-Shoji N., Kurashita K., Terata K., Yamanouchi K., Kubo M., Yumura C., Takahashi Y., Imoto S., Ohno S., Hayashi N.

Breast Cancer 2025

Joint Work, ISSN 13406868

Background: Sentinel lymph node biopsy (SLNB) has become a standard procedure for patients with breast cancer (BC) without clinically evident axillary metastasis. However, its role in cT3-4cN0 BC remains underexplored, leading to uncertainty regarding its safety. Methods: This retrospective, multicenter observational study included patients with cT3-4cN0M0 BC who underwent radical surgery between 2006 and 2016. Patients were divided into an SLNB group, which included those who underwent SLNB exclusively and ALND after SLNB, and an ALND group, which included those who underwent ALND exclusively. Inverse probability treatment weighting was applied to balance the patient characteristics, with recurrence-free survival (RFS) as the primary endpoint. Results: The study included 930 patients: 716 in the SLNB group and 214 in the ALND group. The ALND group had a higher proportion of patients diagnosed earlier, more T4 tumors, and more frequent use of neoadjuvant chemotherapy. During a median follow-up period of 89 months, 176 RFS events and 51 loco-regional recurrence events occurred. After adjusting for confounding factors, no significant difference was found in 10-year RFS between the groups (74.2% vs. 79.2%). Adjusted hazard ratios for RFS did not differ between the groups, even when stratified by tumor stage (cT3, cT4) or neoadjuvant chemotherapy. No significant differences were observed between the SLNB and ALND groups in loco-regional recurrence rate (LRR), with 10-year LRR rates of 93.1% and 90.8%, respectively. Conclusions: SLNB was a safe axillary staging method for patients with cT3-4cN0M0 BC and does not impact RFS or LRR negatively when compared with ALND.

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Axillary surgery in patients with breast cancer with one to three positive micro- or macrometastases in the sentinel lymph nodes: an observational study

Imoto S., Yasojima H., Nagashima T., Onishi T., Takashima T., Kitada M., Kawada M., Hayashida T., Naoi Y., Aihara T., Wada N., Kawabata H., Yoshida M., Toh U., Yoneyama K., Yamada A., Tsuda H., Masuda N., Saito-Oba M., Sakamoto J.

Breast Cancer 2025

Joint Work, ISSN 13406868

Background: The Japanese Society for Sentinel Node Navigation Surgery conducted a multi-institutional prospective cohort study to compare sentinel node biopsy (SNB) with SNB followed by axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel lymph node (SLN). Patients and methods: Female patients with breast cancer with cT1-3N0-1M0 were eligible. In cases of one to three positive micro- or macrometastases in the SLN confirmed by histological or molecular diagnosis, SNB alone (SNB group) or additional ALND (ALND group) was performed under physician’s discretion. The primary endpoint was the 5-year regional node (RN) recurrence rate in the SNB group. Propensity score matching (PSM) was performed to compare the prognosis between the two groups. Results: Of the 871 eligible cases registered between 2013 and 2016, 308 underwent SNB alone. At the median follow-up of 6.3 years, 5-year RN recurrence rate was 2.7%. After PSM, 209 cases were matched in each group. Breast-conserving surgery and mastectomy were performed in 225 (54%) and 193 cases (46%), respectively. One-positive SLN was recorded in 366 cases (88%), two in 48 (11%), and three in 4 (1%). Macro- and micrometastases in SLN were diagnosed in 271 (65%) and 147 cases (35%), respectively. Regional nodal irradiation (RNI) was performed in 42 (20%) and 13 (6%) cases of the SNB and ALND group. The 5-year RN recurrence rate was 2.1% and 2.0%, respectively. Conclusions: ALND is not necessary for early breast cancer patients with one-positive SLN despite type of breast surgery.

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Exploring Breast Cancer Risk Management in HBOC Patients: Image Surveillance Versus Risk-reducing Surgery

Seki Tomoko, Kobayashi Yusuke, Masuda Kenta, Nakamura Kohei, Yamada Mamiko, Goto Yumiko, Misu Kumiko, Ono Ikumi, Nagayama Aiko, Hayashida Tetsu, Kitagawa Yuko

The Keio Journal of Medicine (The Keio Journal of Medicine) advpub ( 0 ) 2025

Joint Work, ISSN 00229717

In Japan, the rising incidence of hereditary breast and ovarian cancer syndrome (HBOC) follows partial insurance coverage introduced in 2020. Compared with the general population (~11% lifetime risk), individuals with HBOC face a significantly higher lifetime risk of breast cancer (48%–76%), often presenting at younger ages. BRCA1 mutations are linked to triple-negative breast cancer, whereas BRCA2 mutations typically result in luminal-type disease. Key risk management strategies include surveillance and prophylactic surgery. Annual magnetic resonance imaging and mammography are recommended at younger ages than in the general population, despite concerns regarding contrast agents, radiation exposure, and examination-related burdens. Although risk-reducing mastectomy lowers breast cancer risk by over 90%, it remains underutilized because of cosmetic and psychological considerations. Nipple-sparing or skin-sparing mastectomy combined with immediate or delayed reconstruction offers a balance between risk reduction and postoperative outcomes, although safety and procedure details still warrant careful evaluation. Managing the high breast cancer risk associated with HBOC requires ongoing efforts to refine current strategies while minimizing patient burden.

An analysis on the effect of body tissues and surgical tools on workflow recognition in first person surgical videos

Tomita H., Ienaga N., Kajita H., Hayashida T., Sugimoto M.

International Journal of Computer Assisted Radiology and Surgery 19 ( 11 ) 2195 - 2202 2024.11

Joint Work, ISSN 18616410

Purpose : Analysis of operative fields is expected to aid in estimating procedural workflow and evaluating surgeons’ procedural skills by considering the temporal transitions during the progression of the surgery. This study aims to propose an automatic recognition system for the procedural workflow by employing machine learning techniques to identify and distinguish elements in the operative field, including body tissues such as fat, muscle, and dermis, along with surgical tools. Methods : We conducted annotations on approximately 908 first-person-view images of breast surgery to facilitate segmentation. The annotated images were used to train a pixel-level classifier based on Mask R-CNN. To assess the impact on procedural workflow recognition, we annotated an additional 43,007 images. The network, structured on the Transformer architecture, was then trained with surgical images incorporating masks for body tissues and surgical tools. Results : The instance segmentation of each body tissue in the segmentation phase provided insights into the trend of area transitions for each tissue. Simultaneously, the spatial features of the surgical tools were effectively captured. In regard to the accuracy of procedural workflow recognition, accounting for body tissues led to an average improvement of 3 % over the baseline. Furthermore, the inclusion of surgical tools yielded an additional increase in accuracy by 4 % compared to the baseline. Conclusion : In this study, we revealed the contribution of the temporal transition of the body tissues and surgical tools spatial features to recognize procedural workflow in first-person-view surgical videos. Body tissues, especially in open surgery, can be a crucial element. This study suggests that further improvements can be achieved by accurately identifying surgical tools specific to each procedural workflow step.

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Phase II clinical trial of docetaxel and trastuzumab for HER2-positive advanced extramammary Paget's disease (EMPD-HER2DOC)

Hirai I., Tanese K., Nakamura Y., Fukuda K., Ouchi T., Hayashida T., Kameyama K., Abe T., Amagai M., Funakoshi T.

Oncologist 29 ( 9 ) e1201 - e1208 2024.09

Joint Work, ISSN 10837159

Background: No consensus has been reached regarding the optimal chemotherapy for metastatic extramammary Paget's disease (EMPD), a rare cutaneous adenocarcinoma, because of the lack of solid evidence from prospective trials. However, the immunohistochemical profile of EMPD reportedly resembles that of breast cancer, particularly in terms of human epidermal growth factor receptor 2 (HER2) expression, suggesting that HER2 is a promising therapeutic target for advanced HER2-positive EMPD. Methods: In this phase II single-arm trial, 13 Japanese patients received intravenous trastuzumab (loading dose of 8 mg/kg and maintenance dose of 6 mg/kg) and docetaxel (75 mg/m2) every 3 weeks for up to 2 years. The docetaxel dose was reduced or discontinued according to its toxicity. The primary trial endpoints were objective response rate (ORR) after 3 cycles of treatment and safety throughout the study period. Results: All 13 patients completed 3 cycles of combination therapy. The median follow-up was 27.9 months. The ORR was 76.9% (n = 10/13; 90% CI, 50.5-93.4). Frequently observed adverse events were neutropenia (100%), hypoalbuminemia (84.6%), and mucocutaneous infection (84.6%), all of which were well tolerated. Conclusion: The combination of docetaxel and trastuzumab demonstrated a favorable clinical effect and acceptable tolerability, which makes it a good treatment option for HER2-positive metastatic EMPD (ClinicalTrials.gov Identifier: UMIN000021311, jRCTs031180073).

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Symptom management through electronic patient-reported outcome (ePRO)-based intervention in patients with breast cancer treated with abemaciclib: Primary results from the LIBRA study, a phase II randomized controlled trial

Takano, T; Hayashida, T; Nagayama, A; Ozaki, Y; Takahashi, M; Seki, T; Yokoe, T; Aoyama, Y; Kizawa, R; Nishimura, M; Hosonaga, M; Hara, F; Kobayashi, T; Ueno, T; Kitagawa, Y

JOURNAL OF CLINICAL ONCOLOGY 42 ( 16 ) 2024.06

Joint Work, ISSN 0732-183X

Proton Pump Inhibitors and Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Breast Cancer

Takahashi K., Uozumi R., Mukohara T., Hayashida T., Iwabe M., Iihara H., Kusuhara-Mamishin K., Kitagawa Y., Tsuchiya M., Kitahora M., Nagayama A., Kosaka S., Asano-Niwa Y., Seki T., Ohnuki K., Suzuki A., Ono F., Futamura M., Kawazoe H., Nakamura T.

Oncologist 29 ( 6 ) e741 - e749 2024.06

Joint Work, ISSN 10837159

Background: Proton pump inhibitors (PPIs) reduce the bioavailability of several anticancer drugs. The impact of PPIs co-Administered with cyclin-dependent kinase 4 and 6 inhibitors is controversial. We aimed to clarify whether the concomitant use of PPIs impacts palbociclib and abemaciclib effectiveness in breast cancer treatment. Patients and Methods: This multicenter, retrospective, observational study, conducted across 4 medical institutions in Japan, consecutively included patients with endocrine-resistant metastatic breast cancer, receiving palbociclib or abemaciclib between December 2017 and August 2022. Propensity score-matched analyses were performed. Treatment efficacy and safety with and without PPIs were compared. Progression-free survival and overall survival were estimated using the Kaplan-Meier method and compared using a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio. Results: The study included 240 patients. After 1:1 matching, 112 patients were treated with and without PPIs. The median progression-free survival period was 1.2 years in the PPI group and 1.3 years in the non-PPI group (hazard ratio, 1.19; 95% CI, 0.70-2.02). The median overall survival period was 3.6 years in the PPI group, whereas it was not reached in the non-PPI group (hazard ratio, 1.23; 95% CI, 0.61-2.47). Consistent results were obtained for subgroups receiving palbociclib (n=177) and abemaciclib (n=63) without propensity score matching. Adverse event incidence and severity were similar in both groups. Conclusion: The effectiveness of cyclin-dependent kinase 4/6 inhibitors is unlikely to be affected by concomitant PPI use. Future prospective pharmacokinetic studies are warranted.

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徹底分析シリーズ痛みのモニタリングへの挑戦 ePROを活用したがん患者の疼痛管理-ePROの現状と課題:LINE-ePROの取り組みについて

四方翔平, 林田哲, 北川雄光

LiSA ((株)メディカル・サイエンス・インターナショナル) 31 ( 5 ) 464 - 468 2024.05

Joint Work, ISSN 13408836

Clinical practice guidelines for molecular tumor marker, 2nd edition review part 2

Kikuchi Y., Shimada H., Yamasaki F., Yamashita T., Araki K., Horimoto K., Yajima S., Yashiro M., Yokoi K., Cho H., Ehira T., Nakahara K., Yasuda H., Isobe K., Hayashida T., Hatakeyama S., Akakura K., Aoki D., Nomura H., Tada Y., Yoshimatsu Y., Miyachi H., Takebayashi C., Hanamura I., Takahashi H.

International Journal of Clinical Oncology 29 ( 5 ) 512 - 534 2024.05

Joint Work, ISSN 13419625

In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, “Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition” was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of “Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition” as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition.

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PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer

Yamamoto T., Hayashida T., Masugi Y., Oshikawa K., Hayakawa N., Itoh M., Nishime C., Suzuki M., Nagayama A., Kawai Y., Hishiki T., Matsuura T., Naito Y., Kubo A., Yamamoto A., Yoshioka Y., Kurahori T., Nagasaka M., Takizawa M., Takano N., Kawakami K., Sakamoto M., Wakui M., Yamamoto T., Kitagawa Y., Kabe Y., Horisawa K., Suzuki A., Matsumoto M., Suematsu M.

Cancer Research 84 ( 7 ) 1065 - 1083 2024.04

Joint Work, ISSN 00085472

Triple-negative breast cancer (TNBC) chemoresistance hampers the ability to effectively treat patients. Identification of mechanisms driving chemoresistance can lead to strategies to improve treatment. Here, we revealed that protein arginine methyltransferase-1 (PRMT1) simultaneously methylates D-3-phosphoglycerate dehydrogenase (PHGDH), a critical enzyme in serine synthesis, and the glycolytic enzymes PFKFB3 and PKM2 in TNBC cells. 13C metabolic flux analyses showed that PRMT1-dependent methylation of these three enzymes diverts glucose toward intermediates in the serine-synthesizing and serine/glycine cleavage pathways, thereby accelerating the production of methyl donors in TNBC cells. Mechanistically, PRMT1-dependent methylation of PHGDH at R54 or R20 activated its enzymatic activity by stabilizing 3-phos-phoglycerate binding and suppressing polyubiquitination. PRMT1-mediated PHGDH methylation drove chemoresistance independently of glutathione synthesis. Rather, activation of the serine synthesis pathway supplied a-ketoglutarate and citrate to increase palmitate levels through activation of fatty acid synthase (FASN). Increased palmitate induced protein S-palmitoylation of PHGDH and FASN to further enhance fatty acid synthesis in a PRMT1-dependent manner. Loss of PRMT1 or pharmacologic inhibition of FASN or protein S-palmitoyltransferase reversed chemoresistance in TNBC. Furthermore, IHC coupled with imaging MS in clinical TNBC specimens substantiated that PRMT1-mediated methylation of PHGDH, PFKFB3, and PKM2 correlates with chemoresistance and that metabolites required for methylation and fatty acid synthesis are enriched in TNBC. Together, these results suggest that enhanced de novo fatty acid synthesis mediated by coordinated protein arginine methylation and protein S-palmitoylation is a therapeutic target for overcoming chemoresistance in TNBC. Significance: PRMT1 promotes chemoresistance in TNBC by methylating metabolic enzymes PFKFB3, PKM2, and PHGDH to augment de novo fatty acid synthesis, indicating that targeting this axis is a potential treatment strategy.

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増刊号 -消化器・一般外科-研修医・専攻医サバイバルブック-術者として経験すべき手技のすべて Ⅱ.体表・体壁乳腺腫瘍生検の適応と手技-吸引細胞診,針生検,マンモトーム生検,切除生検

関朋子, 林田哲, 北川雄光

臨床外科 (株式会社医学書院) 78 ( 11 ) 93 - 97 2023.10

Joint Work, ISSN 03869857

Solitary fibrous tumor of the breast: A case report.

Hirose C, Hayashida T, Saito J, Kubo A, Mikami S, Jinno H

International journal of surgery case reports 108 108369 2023.07

Joint Work, ISSN 2210-2612

Introduction: Solitary fibrous tumors (SFTs) are uncommon mesenchymal neoplasms that comprise <2 % of all soft tissue tumors. They are a diagnostically challenging group of neoplasms that can occur essentially anywhere. Molecular or genetic testing of soft tissue tumors will increasingly add to the foundation of distinctive histologic features, as accurate diagnosis is critical for appropriate treatment. Case presentation: A 28-year-old woman was referred to our hospital for a left breast mass. Ultrasonography showed an oval hypoechoic mass with partially obscured boundaries. Surgical specimens revealed spindle tumor cells surrounding the mammary ducts and were immunoreactive for both CD34 and STAT6, suggesting SFTs. However, the infiltration of spindle tumor cells into the surrounding fat, and the storiform-like pattern made us consider dermatofibrosarcoma protuberans (DFSP) as a differential diagnosis. Lack of amplification of the COL1A1-PDGFB fusion gene, a characteristic feature of DFSP, led to our definitive diagnosis of breast SFT. Discussion: The presence of STAT6 in tumor cell nuclei is a highly sensitive immunohistochemical marker for SFT. In our case, morphological features evoked the differential diagnosis of DFSP and we investigated the COL1A1-PDGFB fusion gene. The diagnostic process of reliably performing careful morphological examination and immunohistochemical marker test, and then obtain conviction by molecular cytogenetic technique is more and more important for soft tissue tumors. Conclusions: We report a quite uncommon case of breast SFT and excluded DFSP as a differential diagnosis. If it is difficult to distinguish between these diseases, molecular cytogenetic analysis would be required for accurate diagnosis.

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Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients.

Nagahashi M, Ling Y, Toshikawa C, Hayashida T, Kitagawa Y, Futamura M, Kuwayama T, Nakamura S, Yamauchi H, Yamauchi T, Kaneko K, Kanbayashi C, Sato N, Tsuchida J, Moro K, Nakajima M, Shimada Y, Ichikawa H, Lyle S, Miyoshi Y, Takabe K, Okuda S, Wakai T

Breast cancer (Tokyo, Japan) 30 ( 4 ) 584 - 595 2023.07

Joint Work, ISSN 1340-6868

Background: Next-generation sequencing (NGS) has enabled comprehensive genomic profiling to identify gene alterations that play important roles in cancer biology. However, the clinical significance of these genomic alterations in triple-negative breast cancer (TNBC) patients has not yet been fully elucidated. The aim of this study was to clarify the clinical significance of genomic profiling data, including copy number alterations (CNA) and tumor mutation burden (TMB), in TNBC patients. Methods: A total of 47 patients with Stage I–III TNBC with genomic profiling of 435 known cancer genes by NGS were enrolled in this study. Disease-free survival (DFS) and overall survival (OS) were evaluated for their association to gene profiling data. Results: CNA-high patients showed significantly worse DFS and OS than CNA-low patients (p = 0.0009, p = 0.0041, respectively). TMB was not associated with DFS or OS in TNBC patients. Patients with TP53 alterations showed a tendency of worse DFS (p = 0.0953) and significantly worse OS (p = 0.0338) compared with patients without TP53 alterations. Multivariable analysis including CNA and other clinicopathological parameters revealed that CNA was an independent prognostic factor for DFS (p = 0.0104) and OS (p = 0.0306). Finally, multivariable analysis also revealed the combination of CNA-high and TP53 alterations is an independent prognostic factor for DFS (p = 0.0005) and OS (p = 0.0023). Conclusions: We revealed that CNA, but not TMB, is significantly associated with DFS and OS in TNBC patients. The combination of CNA-high and TP53 alterations may be a promising biomarker that can inform beyond standard clinicopathologic factors to identify a subgroup of TNBC patients with significantly worse prognosis.

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今月の臨床乳腺-産婦人科医が知っておくべき必須知識乳がんの治療と管理初期治療-外科治療,化学療法・放射線療法

林田哲, 北川雄光

臨床婦人科産科 (株式会社医学書院) 77 ( 3 ) 347 - 352 2023.04

Joint Work, ISSN 03869865

Clinicopathological features, genetic alterations, and BRCA1 promoter methylation in Japanese male patients with breast cancer.

Shimomura A, Yoshida M, Kubo T, Yamashita S, Noguchi E, Nagayama A, Hanamura T, Okazaki M, Mukohara T, Tsuruga A, Tanaka K, Kawamura Y, Higuchi T, Takahashi Y, Kurozumi S, Hayashida T, Ichikawa H, Ushijima T, Suto A

Breast cancer research and treatment 197 ( 3 ) 593 - 602 2023.02

Joint Work, ISSN 0167-6806

Purpose: Male breast cancer (MBC) is a rare cancer accounting for only 1% of all male cancers and is, therefore, poorly studied. We aimed to characterize the subtypes of MBC in Japanese patients based on genetic profiling, the presence of tumor-infiltrating cells, and the expression of immunohistochemical markers. Methods: This retrospective study included 103 patients with MBC diagnosed between January 2009 and December 2019 at various hospitals in Japan. Clinicopathological patient characteristics were obtained from medical records, and formalin-fixed paraffin-embedded tissue specimens were analyzed for histological markers, mutations of 126 genes, BRCA1 methylation, and stromal tumor-infiltrating lymphocytes. Results: The median patient age was 71 (range 31–92) years. T1-stage tumors were the most frequent (47.6%), and most were node negative (77.7%). The majority of tumors were positive for estrogen receptor (98.1%), progesterone receptor (95.1%), and androgen receptor (96.1%), and BRCA2 was the most frequently mutated gene (12.6%). The most common treatment was surgery (99.0%), either total mastectomy (91.1%) or partial mastectomy (7.0%). Survival analysis showed a 5-year recurrence-free survival rate of 64.4% (95% confidence interval [CI] 46.7–88.8) and a 5-year overall survival rate of 54.3% (95% CI 24.1–100.0). Conclusion: Japanese MBC is characterized by a high rate of hormonal receptor positivity and BRCA2 somatic mutation. Due to the observed clinicopathological differences in MBC between the Western countries and Japan, further prospective studies are needed to evaluate the most suitable treatment strategies.

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Polysulfide Serves as a Hallmark of Desmoplastic Reaction to Differentially Diagnose Ductal Carcinoma In Situ and Invasive Breast Cancer by SERS Imaging.

Kubo A, Masugi Y, Hase T, Nagashima K, Kawai Y, Takizawa M, Hishiki T, Shiota M, Wakui M, Kitagawa Y, Kabe Y, Sakamoto M, Yachie A, Hayashida T, Suematsu M

Antioxidants (Basel, Switzerland) 12 ( 2 ) 2023.01

Joint Work, ISSN 2076-3921

Pathological examination of formalin-fixed paraffin-embedded (FFPE) needle-biopsied samples by certified pathologists represents the gold standard for differential diagnosis between ductal carcinoma in situ (DCIS) and invasive breast cancers (IBC), while information of marker metabolites in the samples is lost in the samples. Infrared laser-scanning large-area surface-enhanced Raman spectroscopy (SERS) equipped with gold-nanoparticle-based SERS substrate enables us to visualize metabolites in fresh-frozen needle-biopsied samples with spatial matching between SERS and HE staining images with pathological annotations. DCIS (n = 14) and IBC (n = 32) samples generated many different SERS peaks in finger-print regions of SERS spectra among pathologically annotated lesions including cancer cell nests and the surrounding stroma. The results showed that SERS peaks in IBC stroma exhibit significantly increased polysulfide that coincides with decreased hypotaurine as compared with DCIS, suggesting that alterations of these redox metabolites account for fingerprints of desmoplastic reactions to distinguish IBC from DCIS. Furthermore, the application of supervised machine learning to the stroma-specific multiple SERS signals enables us to support automated differential diagnosis with high accuracy. The results suggest that SERS-derived biochemical fingerprints derived from redox metabolites account for a hallmark of desmoplastic reaction of IBC that is absent in DCIS, and thus, they serve as a useful method for precision diagnosis in breast cancer.

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Fluorodeoxyglucose-positron emission tomography as a potential alternative tool for functional diagnosis of glycogen storage disease type I.

Sato T, Inokuchi M, Nakano S, Iwabuchi Y, Hayashida T, Ishii T, Hasegawa T

Radiology case reports 18 ( 1 ) 91 - 93 2023.01

Joint Work, ISSN 1930-0433

A 43-year-old woman with genetically confirmed glycogen storage disease type Ib was suspected to have left breast cancer. Fluorodeoxyglucose-positron emission tomography showed high fluorodeoxyglucose accumulation in the whole liver as well as left mammary gland. We consider that high fluorodeoxyglucose accumulation in the liver of patients with glycogen storage disease type I is caused by impaired glucose-6-phosphate metabolism due to the congenital deficiency of glucose-6-phosphatase activities in hepatocytes. This study describes fluorodeoxyglucose-positron emission tomography as a potential alternative tool to diagnose glycogen storage disease type I functionally.

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Establishment of a deep-learning system to diagnose BI-RADS4a or higher using breast ultrasound for clinical application.

Hayashida T, Odani E, Kikuchi M, Nagayama A, Seki T, Takahashi M, Futatsugi N, Matsumoto A, Murata T, Watanuki R, Yokoe T, Nakashoji A, Maeda H, Onishi T, Asaga S, Hojo T, Jinno H, Sotome K, Matsui A, Suto A, Imoto S, Kitagawa Y

Cancer science 113 ( 10 ) 3528 - 3534 2022.10

Joint Work, ISSN 1347-9032

Although the categorization of ultrasound using the Breast Imaging Reporting and Data System (BI-RADS) has become widespread worldwide, the problem of inter-observer variability remains. To maintain uniformity in diagnostic accuracy, we have developed a system in which artificial intelligence (AI) can distinguish whether a static image obtained using a breast ultrasound represents BI-RADS3 or lower or BI-RADS4a or higher to determine the medical management that should be performed on a patient whose breast ultrasound shows abnormalities. To establish and validate the AI system, a training dataset consisting of 4028 images containing 5014 lesions and a test dataset consisting of 3166 images containing 3656 lesions were collected and annotated. We selected a setting that maximized the area under the curve (AUC) and minimized the difference in sensitivity and specificity by adjusting the internal parameters of the AI system, achieving an AUC, sensitivity, and specificity of 0.95, 91.2%, and 90.7%, respectively. Furthermore, based on 30 images extracted from the test data, the diagnostic accuracy of 20 clinicians and the AI system was compared, and the AI system was found to be significantly superior to the clinicians (McNemar test, p < 0.001). Although deep-learning methods to categorize benign and malignant tumors using breast ultrasound have been extensively reported, our work represents the first attempt to establish an AI system to classify BI-RADS3 or lower and BI-RADS4a or higher successfully, providing important implications for clinical actions. These results suggest that the AI diagnostic system is sufficient to proceed to the next stage of clinical application.

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Comparison between a new assay system, Elecsys(®) Anti-p53, and conventional MESACUP™ for the detection of serum anti-p53 antibodies: A multi-institutional study.

Suzuki T, Oshima Y, Shiratori F, Nanami T, Yajima S, Sumazaki M, Ushigome M, Sugita H, Eberl M, Ogata H, Hayashida T, Nakamura S, Nakagawa T, Shimada H

Molecular and clinical oncology 17 ( 2 ) 130 2022.08

Joint Work, ISSN 2049-9450

The sensitivity and specificity of a new automated electrochemiluminescence immunoassay system, Elecsys® Anti-p53 (Elecsys), were compared with that of the conventional serum anti-p53 antibody (s-p53-Ab) enzyme-linked immunosorbent assay kit [MESACUP anti-p53 test (MESACUP)]. Elecsys and MESACUP were used to analyze the levels of s-p53-Abs in patients with esophageal, colorectal and breast cancer. A total of 532 controls and 288, 235 and 329 patients with esophageal, colorectal and breast cancer, respectively, were enrolled. Additionally, the sera of patients with benign diseases of the esophagus, colorectal system and breast, patients with autoimmune diseases and healthy volunteers were analyzed as controls. Sensitivity and specificity were compared between the two assay systems. Positive agreement rates were 58.7% in all samples, 71.2% in esophageal samples, 73.6% in colorectal samples and 35.1% in breast samples. Negative agreement rates for the different cancer types were ≥97.1% and the overall agreement rates were ≥92.3%. When the specificities of the two assays were aligned for all samples, Elecsys demonstrated higher sensi-tivities for all types of analyzed cancer together, as well as for esophageal, colorectal and breast cancer, respectively. Although positive concordance between the two assay systems was low in terms of specificity, Elecsys had a higher sensitivity than the MESACUP.

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Observational study of axilla treatment for breast cancer patients with 1 to 3 positive micrometastases or macrometastases in sentinel lymph nodes.

Yasojima, H; Imoto, S; Nagashima, T; Onishi, T; Takashima, T; Kitada, M; Kawada, M; Hayashida, T; Naoi, Y; Aihara, T; Wada, N; Kawabata, H; Yoshida, M; Toh, U; Yoneyama, K; Yamada, A; Tsuda, H; Masuda, N; Saito-Oba, M; Sakamoto, J

JOURNAL OF CLINICAL ONCOLOGY 40 ( 16 ) 2022.06

Joint Work, ISSN 0732-183X

Feasibility study on collecting patient-reported outcomes from breast cancer patients using the LINE-ePRO system.

Hayashida T, Nagayama A, Seki T, Takahashi M, Matsumoto A, Kubota A, Jinno H, Miyata H, Kitagawa Y

Cancer science 113 ( 5 ) 1722 - 1730 2022.05

Joint Work, ISSN 1347-9032

Due to the increasing complexity of cancer treatment, ensuring safety and maintaining the quality of life during treatment are important issues. Patient-reported outcomes (PROs) in oncology are essential for assessing patient symptoms. A feasibility study was undertaken on breast cancer patients by building a PRO data collection system based on LINE, one of the most popular social network service applications in Japan. In this study, one or more predefined PRO questions for each breast cancer patient's clinical situation were sent to the patient’s LINE application daily. The patient selected a predefined answer by tapping the screen, but no free-text answers were allowed. Seventy-three patients were enrolled. The median observation period was 435 days (84-656 days), and the total number of PROs collected was 16,417, with a mean of 224.9 reports per patient. Patients on adjuvant endocrine therapy were notified of 2.5 questions per week, and the median number of responses per week and response rate were 2.387 (1.687-11.627) and 95.5%, respectively. Analyzing the results by age group, the number of responses from those aged 60 and above was equal to or higher than that of the younger age group. It was also possible to track each patient’s PROs accurately. These results suggested that the design of the system, based on an application used daily, instead of using specifically prepared applications for collecting electronic PROs, was the reason for the favorable acceptance from patients and the satisfactory response rate from all age groups, including the elderly.

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Spatiotemporal Video Highlight by Neural Network Considering Gaze and Hands of Surgeon in Egocentric Surgical Videos

Yoshida K., Hachiuma R., Tomita H., Pan J., Kitani K., Kajita H., Hayashida T., Sugimoto M.

Journal of Medical Robotics Research 7 ( 1 ) 2022.03

Joint Work, ISSN 2424905X

In the medical field, surgical videos can be used to introduce surgical skills. Medical students and residents watch the videos to study the surgical skills and increase learning speed by compensating for the lack of experience in surgical rooms due to limited opportunity to join in surgery. To record egocentric surgical videos by a wearable camera is a solution to record surgical skills of a surgeon in detail. However, most egocentric surgical videos are of quite long duration. For example, in the case of tumor removal in breast surgery, a video recording time often reaches 2h. With that length, it is time consuming to see important scenes in the video, particularly because many surgical videos include nonessential scenes such as sterilization and preparation of tools. For extracting specific scenes from a long video, we can apply scene estimation by machine learning. Furthermore, it is important to know where the surgeon is looking to observe the area of the incision in detail. In particular, it is vital to be able to zoom in on key elements, allowing viewers to see the incision area and the fine details of the necessary surgical skills. In this study, we aimed to highlight incision scenes from egocentric surgical videos in the spatiotemporal domain by utilizing two neural networks for the temporal and spatial highlights. For the temporal highlights, we designed a neural network that estimates the incision scenes by learning gaze speed, hand movements, number of hands, and background movements in egocentric surgical videos. For the spatial highlights, in order to estimate the important area to zoom in, we designed a neural network that learns the surgeon's gaze on natural features of surgical scenes to form a probability map as a representation of the estimated gaze area. The estimated gaze area was also used to calculate the appropriate zoom-in position and zoom-in ratio. To control the highlighted parameters in accord with user preferences, we also made a user interface that allows for the selection of playback speed gain and zoom ratio gain. For the evaluation, we verified the performance of the networks by a quantitative assessment and conducted a user study with medical doctors by showing an actual surgical video to obtain a qualitative assessment on the proposed system.

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The relationship between work-related outcomes and symptoms in early breast cancer survivors receiving adjuvant endocrine therapy.

Nakao M, Komatsu H, Hayashida T, Takahashi M, Seki T, Yagasaki K

Asia-Pacific journal of oncology nursing 9 ( 3 ) 174 - 178 2022.03

Joint Work, ISSN 2347-5625

Objective: This study examined the relationship between symptom burdens and work-related outcomes, including work participation and overall work impairment (OWI) among breast cancer survivors (BCS) receiving adjuvant endocrine therapy (AET). Methods: This was a cross-sectional study with 140 BCS of working age receiving AET. Data were collected using self-report questionnaires that included an assessment of symptoms and their employment status, and OWI. Data were analyzed using descriptive statistics and multiple logistic regression analysis. Results: A total of 111 (79%) survivors reported being employed at the time of the survey. Symptom burdens were not associated with unemployment. Of the 110 working BCS receiving AET, symptom burdens were significantly related to a higher degree of OWI (OR = 2.14, 95% CI, 1.58–2.89, P ≤ 0.001). Conclusions: Participating BCS receiving AET continued to work while experiencing symptoms, with survivors who experienced high symptom burdens being negatively affected in their work life. Healthcare providers need to assess and manage symptoms and their impact on work, with the help of employers, to improve the quality of work life of BCS receiving AET.

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乳房超音波検査におけるAI診断システムの開発

林田哲, 小谷依里奈, 永山愛子, 関朋子, 高橋麻衣子, 北川雄光

Japanese Journal of Medical Ultrasound Technology Supplement (Japanese Society of Sonographers) 47 ( 0 ) S82 - S82 2022

Joint Work

特集 AIは外科にどこまで役立つか I. 総論 2.手術映像におけるAIによる時間的・空間的推定技術の確立と応用

杉本麻樹, 梶田大樹, 林田哲, 北川雄光

外科 (南江堂) 83 ( 11 ) 1160 - 1165 2021.10

Joint Work, ISSN 0016593X

Appropriate use of cancer comprehensive genome profiling assay using circulating tumor DNA.

Sunami K, Bando H, Yatabe Y, Naito Y, Takahashi H, Tsuchihara K, Toyooka S, Mimori K, Kohsaka S, Uetake H, Kinoshita I, Komine K, Takeda M, Hayashida T, Tamura K, Nishio K, Yamamoto N, Working Group of a Joint Task Force of Three Academic Societies for the Promotion of Cancer Genomic Medicine

Cancer science 112 ( 9 ) 3911 - 3917 2021.09

Joint Work, ISSN 1347-9032

Comprehensive genomic profiling (CGP) is being increasingly used for the routine clinical management of solid cancers. In July 2018, the use of tumor tissue-based CGP assays became available for all solid cancers under the universal health insurance system in Japan. Several restrictions presently exist, such as patient eligibility and limitations on the opportunities to perform such assays. The clinical implementation of CGP based on plasma circulating tumor DNA (ctDNA) is also expected to raise issues regarding the selection and use of tissue DNA and ctDNA CGP. A Joint Task Force for the Promotion of Cancer Genome Medicine comprised of three Japanese cancer-related societies has formulated a policy proposal for the appropriate use of plasma CGP (in Japanese), available at https://www.jca.gr.jp/researcher/topics/2021/files/20210120.pdf, http://www.jsco.or.jp/jpn/user_data/upload/File/20210120.pdf, and https://www.jsmo.or.jp/file/dl/newsj/2765.pdf. Based on these recommendations, the working group has summarized the respective advantages and cautions regarding the use of tissue DNA CGP and ctDNA CGP with reference to the advice of a multidisciplinary expert panel, the preferred use of plasma specimens over tissue, and multiple ctDNA testing. These recommendations have been prepared to maximize the benefits of performing CGP assays and might be applicable in other countries and regions.

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Recovery of lower oesophageal barrier function: a pilot study comparing a mixture of atropine and neostigmine and sugammadex A randomised controlled pilot study

Suganuma, E; Ishikawa, T; Kitamura, Y; Hayashida, T; Matsumura, T; Fujie, M; Nozaki-Taguchi, N; Sato, Y; Isono, S

EUROPEAN JOURNAL OF ANAESTHESIOLOGY 38 ( 8 ) 856 - 864 2021.08

Joint Work, ISSN 0265-0215

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A transposon screen identifies enhancement of NF-κB pathway as a mechanism of resistance to eribulin.

Teng X, Hayashida T, Murata T, Nagayama A, Seki T, Takahashi M, Kitagawa Y

Breast cancer (Tokyo, Japan) 28 ( 4 ) 884 - 895 2021.07

Joint Work, ISSN 1340-6868

Background: Eribulin mesylate (eribulin) is an efficient microtubule inhibitor that is used for metastatic breast cancer. However, breast cancer can develop resistance to eribulin. This resistance mechanism needs to be elucidated. Methods: A transposon mutagenesis screen was conducted using a pPB-SB-CMV-puro-SD plasmid and pCMV-PBase transposase. Viability and cytotoxicity were analyzed by MTT assay and flow cytometry, respectively. Real-time PCR and western blot were used for gene expression analysis. In addition, vivo study was also designed to analyze therapy efficiency. Results: TAB2, which is part of the nuclear factor-kappa B (NF-κB) pathway, was identified as a candidate eribulin-resistant gene. TAB2 down-regulation resulted in significantly lower cell viability and higher cytotoxicity of cells treated with eribulin, while TAB2 up-regulation showed opposite results. Similarly, combination of NF-κB inhibitors [Bay-117082 and QNZ (quinazoline derivative)] with eribulin showed significantly lower cell viability and higher drug cytotoxicity than single agent treatment with eribulin in MDA-MB-231 cells. However, QNZ increased NF-κB activity in MCF7 cells by up-regulating TAB2, which reduced the sensitivity to eribulin. Furthermore, combination of Bay-117082 with eribulin induced greater regression of MDA-MB-231 tumors compared to eribulin monotherapy in vivo. Conclusions: These results consistently illustrated that TAB2-NF-κB pathway may increases resistance to eribulin in breast cancer models. Moreover, these results support the use of a combination strategy of eribulin with NF-κB inhibitors, and provide evidence that transposon mutagenesis screens are capable of identifying drug-resistant genes.

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Comprehensive analysis of the homeobox family genes in breast cancer demonstrates their similar roles in cancer and development.

Nakashoji A, Hayashida T, Yamaguchi S, Kawai Y, Kikuchi M, Yokoe T, Nagayama A, Seki T, Takahashi M, Kitagawa Y

Breast cancer research and treatment 186 ( 2 ) 353 - 361 2021.04

Joint Work, ISSN 0167-6806

Background: The homeobox (HOX) family consists of 39 genes whose expressions are tightly controlled and coordinated within the family, during development. We performed a comprehensive analysis of this gene family in cancer settings. Methods: Gene correlation analysis was performed using breast cancer data available in The Cancer Genome Atlas (TCGA) and data from the patients admitted to our hospital. We also analyzed the data of normal breast tissue (GSE20437). We next collected gene expression and prognosis data of breast cancer patients (GSE11121, GSE7390, GSE3494, and GSE2990) and performed unsupervised hierarchal clustering by the HOX gene expression pattern and compared prognosis. We additionally performed this analysis to leukemia (available in TCGA) and sarcoma (GSE20196) data. Results: Gene correlation analysis showed that the proximal HOX genes exhibit strong interactions and are expressed together in breast cancer, similar to the expression observed during development. However, in normal breast tissue, less interactions were observed. Breast cancer microarray meta-data classified by the HOX gene expression pattern predicted the prognosis of luminal B breast cancer patients (p = 0.016). Leukemia (p = 0.00016) and sarcoma (p = 0.018) presented similar results. The Wnt signaling pathway, one of the major upstream signals of HOX genes in development, was activated in the poor prognostic group. Interestingly, poor prognostic cancer presented stronger correlation in the gene family compared to favorable prognostic cancer. Conclusion: Comprehensive analysis of the HOX family demonstrated their similar roles in cancer and development, and indicated that the strong interaction of HOX genes might be specific to malignancies, especially in the case of poor prognostic cancer.

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Estimating copy number using next-generation sequencing to determine ERBB2 amplification status.

Nakamura K, Aimono E, Oba J, Hayashi H, Tanishima S, Hayashida T, Chiyoda T, Kosaka T, Hishida T, Kawakubo H, Kitago M, Okabayashi K, Funakoshi T, Okita H, Ikeda S, Takaishi H, Nishihara H

Medical oncology (Northwood, London, England) 38 ( 4 ) 36 2021.03

Joint Work, ISSN 1357-0560

Assessing Erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification status in breast and gastric cancer is necessary for deciding the best therapeutic strategy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently used for assessing protein levels and gene copy number (CN), respectively. The use of next-generation sequencing (NGS) to measure ERBB2 CN in breast cancer is approved by the United States Federal Drug Administration as a companion diagnostic. However, a CN of less than 8 is evaluated as “equivocal”, which means that some ERBB2 amplification cases diagnosed as “HER2 negative” might be false-negative cases. We reviewed the results of gene profiling targeting 160 cancer-related genes in breast (N = 90) and non-breast (N = 19) cancer tissue, and compared the ERBB2 CN results with the IHC/FISH scores. We obtained an estimated CN from the measured CN by factoring in the histological proportion of tumor cells and found that an ERBB2-estimated CN of 3.2 or higher was concordant with the combined IHC/FISH outcome in 98.4% (88/90) of breast cancer cases, while this was not always evident among non-breast cancer cases. Therefore, NGS-estimated ERBB2 CN could be considered a diagnostic test for anti-HER2 therapy after the completion of adequate prospective clinical trials.

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Predictors of invasive disease in patients preoperatively diagnosed with ductal carcinoma without stromal invasion, with breast magnetic resonance imaging (MRI) and ultrasound (US).

Maeda H, Hayashida T, Watanuki R, Kikuchi M, Nakashoji A, Yokoe T, Seki T, Takahashi M, Kitagawa Y

Breast cancer (Tokyo, Japan) 28 ( 2 ) 398 - 404 2021.03

Joint Work, ISSN 1340-6868

Background: A preoperative diagnosis of ductal carcinoma in situ (DCIS) is sometimes upstaged to invasive disease postoperatively. Our objective was to clarify the predictive factors of invasive disease using preoperative imaging and to investigate the positive ratio of sentinel lymph nodes (SLN) and the incidence of invasive disease. Methods: The subjects were 402 patients with preoperatively diagnosed ductal carcinoma without stromal invasion who underwent breast surgery with concomitant SLN surgery in January 2007 to December 2016. Of the 306 included patients, all 306 patients underwent preoperative MRI and US assessment. Outcomes were analyzed for significance using univariate and multivariate analyses. Results: Of the 306 patients, 115 (37.6%) had invasive disease and 191 (62.4%) had DCIS only. Of the 115 patients with invasive disease, 5 (4.4%) and 4 (3.5%) had macro- and micrometastases in SLN. On the other hand, of the 191 patients with DCIS, only 1 (0.5%) had a micrometastasis. Predictors of invasive disease in the univariate analysis included having a palpable mass, were varied by biopsy method, having a US hypoechoic mass, MRI enhancement, or MRI large enhanced lesion; the size of the mass enhancement ≥ 1.1 cm or a spread of non-mass enhancement ≥ 3.1 cm (P = 0.003). Predictors of invasive disease in the multivariate analysis included US hypoechoic mass and MRI large enhanced lesion. Conclusion: We need to perform SLN biopsy for preoperatively diagnosed DCIS when patients have predictors of invasive disease, but SLN biopsy will no longer be essential for patients when they have no predictors of invasive disease.

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Association of chemotherapy-induced peripheral neuropathy, physical activity and health-related quality of life among breast cancer patients

Sugimoto Miki, Komatsu Hiroko, Hayashida Tetsu

Journal of Japanese Society of Cancer Nursing (Japanese Society of Cancer Nursing) 35 ( 0 ) n/a 2021.02

Joint Work, ISSN 09146423

The purpose of this study was to gain insights into the relationship between chemotherapy-induced peripheral neuropathy (CIPN), physical activity, and health-related quality of life (HRQOL) in breast cancer patients who received taxane-based chemotherapy. We conducted a cross-sectional, observational study on 43 breast cancer patients who underwent taxane-based chemotherapy. Information on demographics, CIPN (Ntx subscale), HRQOL (FACT-G), physical activity (IPAQ-SF), and psychological distress (K6) was collected through self-administered questionnaires. Data of clinical characteristics were extracted from the patients' medical records. Correlation analysis revealed a significant positive correlation between CIPN and HRQOL (r = 0.55, p < 0.001), physical well-being (r = 0.72, p < 0.001), emotional well-being (r = 0.41, p < 0.01), and functional well-being (r = 0.47, p < 0.01) but not physical activity. There was no significant correlation between physical activity and HRQOL. Among the 19 patients with severe symptoms of CIPN, an analysis of physical activity showed that 7 (36.8%) were inactive and 12 (63.2%) were active. Hence, CIPN significantly affects the HRQOL of breast cancer patients. Additionally, some patients perform physical activity according to their individual roles and environment by managing and enduring the symptoms of CIPN. Nurses should recognize the impact of CIPN on patients’ everyday lives, adequately assess the CIPN symptoms, evaluate the influence of CIPN on patients’ physical activity levels, and counsel patients accordingly. Additionally it is necessary to consider patients individually how to perform physical activity safely, especially when experiencing CIPN.

Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (edition 2.1).

Naito Y, Aburatani H, Amano T, Baba E, Furukawa T, Hayashida T, Hiyama E, Ikeda S, Kanai M, Kato M, Kinoshita I, Kiyota N, Kohno T, Kohsaka S, Komine K, Matsumura I, Miura Y, Nakamura Y, Natsume A, Nishio K, Oda K, Oda N, Okita N, Oseto K, Sunami K, Takahashi H, Takeda M, Tashiro S, Toyooka S, Ueno H, Yachida S, Yoshino T, Tsuchihara K, Japanese Society of Medical Oncology, Japan Society of Clinical Oncology, Japanese Cancer Association

International journal of clinical oncology 26 ( 2 ) 233 - 283 2021.02

Joint Work, ISSN 1341-9625

Background: To promote precision oncology in clinical practice, the Japanese Society of Medical Oncology, the Japanese Society of Clinical Oncology, and the Japanese Cancer Association, jointly published “Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment” in 2017. Since new information on cancer genomic medicine has emerged since the 1st edition of the guidance was released, including reimbursement for NGS-based multiplex gene panel tests in 2019, the guidance revision was made. Methods: A working group was organized with 33 researchers from cancer genomic medicine designated core hospitals and other academic institutions. For an impartial evaluation of the draft version, eight committee members from each society conducted an external evaluation. Public comments were also made on the draft. The finalized Japanese version was published on the websites of the three societies in March 2020. Results: The revised edition consists of two parts: an explanation of the cancer genomic profiling test (General Discussion) and clinical questions (CQs) that are of concern in clinical practice. Particularly, patient selection should be based on the expectation that the patient's post-test general condition and organ function will be able to tolerate drug therapy, and the optimal timing of test should be considered in consideration of subsequent treatment plans, not limited to treatment lines. Conclusion: We expect that the revised version will be used by healthcare professionals and will also need to be continually reviewed in line with future developments in cancer genome medicine.

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【乳癌診療におけるAIの応用:画像診断、病理診断、データ解析の分野など】乳房超音波AIの実用化に向けた研究開発

Hayashida Tetsu

乳癌の臨床 36 31 - 37 2021

Joint Work

CiNii Research

Camera Selection for Occlusion-Less Surgery Recording via Training with an Egocentric Camera

Saito Y., Hachiuma R., Saito H., Kajita H., Takatsume Y., Hayashida T.

IEEE Access 9 138307 - 138322 2021

Joint Work, ISSN 2169-3536

Recording surgery is an important technique for education and the evaluation of medical treatments. However, capturing targets such as the surgical field, surgical tools, and the surgeon's hands, is almost impossible since these targets are heavily occluded by the surgeon's head and body during a surgery. We used a recording system in which multiple cameras are installed in the surgical lump, supposing at least one camera would capture the target without occlusion. As this system records multiple video sequences, we address the task to select a best view camera automatically. Recently, learning-based approaches in a fully supervised manner have been proposed for this task, but these previous approaches completely rely on manual annotation of the training data. In this paper, we focus on the eye tracker mounted on the surgeon's head, which can capture the recording targets without occlusion. Employing this first-person-view video synchronized with multiple videos of the surgical lump, we propose a novel camera selection approach using a self-supervised learning framework. In experiments, we created a dataset composed of four different breast surgery. Our extended experiments showed that our approach successfully switched to the best camera view without manual annotation and achieved competitive accuracy compared with conventional supervised methods. Also, our approach yielded effective visual representations comparable to state-of-the-art self-supervised learning frameworks.

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Impact of neoadjuvant and adjuvant chemotherapy on invasive lobular carcinoma: A propensity score-matched analysis of SEER data.

Watanuki R, Hayashida T, Yokoe T, Kawai Y, Kikuchi M, Nakashoji A, Nagayama A, Seki T, Takahashi M, Kitagawa Y

The breast journal 26 ( 9 ) 1765 - 1770 2020.09

Joint Work, ISSN 1075-122X

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Mindfulness-Based Cognitive Therapy for Psychological Distress, Fear of Cancer Recurrence, Fatigue, Spiritual Well-Being, and Quality of Life in Patients With Breast Cancer-A Randomized Controlled Trial.

Park S, Sato Y, Takita Y, Tamura N, Ninomiya A, Kosugi T, Sado M, Nakagawa A, Takahashi M, Hayashida T, Fujisawa D

Journal of pain and symptom management 60 ( 2 ) 381 - 389 2020.08

Joint Work, ISSN 0885-3924

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Increased frequency of ESR1 mutation in metastatic breast cancer by dosing selective estrogen receptor modulator followed by aromatase inhibitor.

Takeshima K, Hayashida T, Maeda H, Nakashoji A, Yokoe T, Seki T, Takahashi M, Kitagawa Y

Oncology letters 20 ( 2 ) 1231 - 1238 2020.08

Joint Work, ISSN 1792-1074

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A novel diagnostic system to evaluate epidermal growth factor receptor impact as a prognostic and therapeutic indicator for lung adenocarcinoma.

Takakuwa K, Mogushi K, Han M, Fujii T, Hosoya M, Yamanami A, Akita T, Yamashita C, Hayashida T, Kato S, Yamaguchi S

Scientific reports 10 ( 1 ) 6214 2020.04

Joint Work

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Evaluation of the Japanese Version of the Cancer Survivors' Unmet Needs Scale.

Komatsu H, Yagasaki K, Sato Y, Arao H, Yamamoto S, Hayashida T

Asia-Pacific journal of oncology nursing 7 ( 2 ) 167 - 173 2020.04

Joint Work, ISSN 2347-5625

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Identification of a Modified HOXB9 mRNA in Breast Cancer.

Nakashoji A, Hayashida T, Kawai Y, Kikuchi M, Watanuki R, Yokoe T, Seki T, Takahashi M, Miyao K, Yamaguchi S, Kitagawa Y

Journal of oncology 2020 6065736 2020

Joint Work, ISSN 1687-8450

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A first Japanese case of neuroendocrine prostate cancer accompanied by lung and brain metastasis with somatic and germline BRCA2 mutation.

Kosaka T, Hongo H, Aimono E, Matsumoto K, Hayashida T, Mikami S, Nishihara H, Oya M

Pathology international 69 ( 12 ) 715 - 720 2019.12

Research paper (scientific journal), Joint Work, Accepted, ISSN 1320-5463

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THUMP domain containing 2 protein possibly induces resistance to cisplatin and 5-fluorouracil in in vitro human esophageal squamous cell carcinoma cells as revealed by transposon activation mutagenesis.

Hayashi M, Kawakubo H, Fukuda K, Mayanagi S, Nakamura R, Suda K, Hayashida T, Wada N, Kitagawa Y

The journal of gene medicine 21 ( 12 ) e3135 2019.12

Joint Work, ISSN 1099-498X

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Intensive optimization and evaluation of global DNA methylation quantification using LC-MS/MS.

Nakagawa T, Wakui M, Hayashida T, Nishime C, Murata M

Analytical and bioanalytical chemistry 411 ( 27 ) 7221 - 7231 2019.10

Research paper (scientific journal), Joint Work, Accepted, ISSN 1618-2642

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Magnetically Promoted Rapid Immunofluorescence Staining for Frozen Tissue Sections

Onishi T., Matsuda S., Nakamura Y., Kuramoto J., Tsuruma A., Sakamoto S., Suzuki S., Fuchimoto D., Onishi A., Chikaki S., Kaneko M., Kuwahata A., Sekino M., Yasuno H., Hanyu N., Kurita T., Takei H., Sakatani T., Taruno K., Nakamura S., Hayashida T., Jinno H., Kusakabe M., Handa H., Kameyama K., Kitagawa Y.

Journal of Histochemistry and Cytochemistry (Journal of Histochemistry and Cytochemistry) 67 ( 8 ) 575 - 587 2019.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 00221554

© The Author(s) 2019. Current immunohistochemistry methods for diagnosing abnormal cells, such as cancer cells, require multiple steps and can be relatively slow compared with intraoperative frozen hematoxylin and eosin staining, and are therefore rarely used for intraoperative examination. Thus, there is a need for novel rapid detection methods. We previously demonstrated that functionalized fluorescent ferrite beads (FF beads) magnetically promoted rapid immunoreactions. The aim of this study was to improve the magnetically promoted rapid immunoreaction method using antibody-coated FF beads and a magnet subjected to a magnetic field. Using frozen sections of xenograft samples of A431 human epidermoid cancer cells that express high levels of epidermal growth factor receptor (EGFR) and anti-EGFR antibody-coated FF beads, we reduced the magnetically promoted immunohistochemistry procedure to a 1-min reaction and 1-min wash. We also determined the optimum magnetic force for the antibody reaction (from 7.79 × 10−15 N to 3.35 × 10−15 N) and washing (4.78 × 10−16 N), which are important steps in this technique. Furthermore, we stained paraffin-embedded tissue arrays and frozen sections of metastatic breast cancer lymph nodes with anti-pan-cytokeratin antibody-coated FF beads to validate the utility of this system in clinical specimens. Under optimal conditions, this ultra-rapid immunostaining method may provide an ancillary method for pathological diagnosis during surgery. (J Histochem Cytochem 58:XXX–XXX, 2010).

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Optimal use of anthracycline-free perioperative chemotherapy in HER2-positive breast cancer patients

Watanuki R., Hayashida T., Kawai Y., Kikuchi M., Nakashoji A., Yokoe T., Toyota T., Seki T., Takahashi M., Kitagawa Y.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 24 ( 7 ) 807 - 814 2019.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 13419625

© 2019, Japan Society of Clinical Oncology. Purpose: In adjuvant settings of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, anthracycline-based chemotherapy followed by taxane and trastuzumab is a standard regimen. Recent studies have reported the use of anthracycline-free adjuvant chemotherapy in selected HER2-positive breast cancer patients. We conducted a single-center retrospective study to identify the characteristics of HER2-positive breast cancer patients for whom anthracyclines can be safely omitted. Methods: A total of 238 women were diagnosed with HER2-positive breast cancer and treated with neoadjuvant and/or adjuvant chemotherapy between January 1, 2008 and December 31, 2015 at Keio University Hospital. They were divided in two cohorts: an “anthracycline” cohort of 112 anthracycline-treated women and a “no anthracycline” cohort of 126 anthracycline-untreated women. Survival outcomes were estimated by Kaplan–Meier method. Results: The 3-year disease-free survival rates in the no-anthracycline and anthracycline cohorts were 91.3% and 93.1%, respectively (P = 0.692). After using a statistical method with inverse probability of treatment weighting to minimize the selection bias, no significant differences were observed between the two cohorts (adjusted hazard ratio for disease-free survival: 1.042; P = 0.909). Stratified by tumor size, no significant differences were observed between the two cohorts in the cT1N0 and cT2N0 subsets (P = 0.516 and P = 0.579, respectively). The recurrence rate was low among patients who achieved pathological complete response after receiving neoadjuvant chemotherapy with or without anthracyclines. Conclusion: Our study suggests that anthracyclines can be safely omitted in selected patients with HER2-positive breast cancer, who have cT1N0 or cT2N0 and achieved pathological complete response after receiving neoadjuvant chemotherapy.

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Effectiveness of Antiemetic Regimens for Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Network Meta-Analysis

Yokoe T., Hayashida T., Nagayama A., Nakashoji A., Maeda H., Seki T., Takahashi M., Takano T., Abe T., Kitagawa Y.

Oncologist (Oncologist) 24 ( 6 ) e347 - e357 2019.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 10837159

© AlphaMed Press 2018 Background: It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer Network guidelines suggest combination therapy of antiemetic agents. The growing number of antiemetic regimens, and in particular the growing use of regimens containing antagonists to the Nk-1 receptor (NK1RAs) and the antipsychotic drug olanzapine (OLZ), call for the re-evaluation of the optimal regimen for CINV. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy, using Bayesian network meta-analysis. Methods: Randomized trials that compared different antiemetic regimens were included. We strictly followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The main outcomes were the odds ratio (OR) for overall complete response (absence of vomiting). We conducted network meta-analysis within a Bayesian model to combine the direct and indirect evidence. Safety was assessed from the trial description. All statistical tests were two-sided. Results: We systematically reviewed 27 randomized control trials (13,356 participants), which compared 12 different antiemetic regimens: serotonin-3 receptor antagonist (5HT3), 5HT3 + dexamethasone (Dex), palonosetron (PAL), PAL + Dex, PAL at 0.75 mg (PAL0.75), PAL0.75 + Dex, NK1RA + 5HT3 + Dex, NK1RA + PAL + Dex, an oral combination of netupitant and palonosetron (NEPA) + Dex, OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + NK1RA + 5HT3 + Dex. An NK1RA + 5HT3 + Dex regimen and an NK1RA + palonosetron + Dex regimen gave a higher complete response (CR) rate than the reference regimen, 5HT3 + Dex (OR, 1.75; 95% credibility interval [95% CrI], 1.56–1.97, and OR, 2.25; 95% CrI, 1.66–3.03, respectively). A regimen containing NEPA was more effective in producing CR than conventional regimens without NEPA or olanzapine. Further analysis, based on the surface under the cumulative ranking probability curve, indicated that olanzapine-containing regimens were the most effective in producing CR. Conclusion: Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients. Implications for Practice: Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.

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Establishment of a model of sentinel lymph node metastasis using immunodeficient swine

Kurihara T., Matsuda S., Nakamura Y., Suzuki S., Fuchimoto D., Onishi A., Saeki K., Nakagawa T., Fujiwara R., Kamata M., Kuramoto J., Kameyama K., Sekino M., Kusakabe M., Hayashida T., Jinno H., Kitagawa Y.

Scientific reports (Scientific reports) 9 ( 1 ) 7923 2019.05

Research paper (scientific journal), Joint Work, Accepted

Lymph node metastasis occurs via the migration of cancer cells through the lymphatic system. Sentinel lymph node (SLN) biopsy is a common diagnostic strategy. SLNs have been studied using healthy rodents and large animals without metastasis. Here we used immunodeficient swine to establish a model of lymph node metastasis. We used RAG2-knockout immunodeficient swine. A431 human epithelial carcinoma cells expressing green fluorescent protein were injected subcutaneously into the posterior sides of the auricle, forelimb and hindlimb of knockout swine. Indigo carmine dye was injected subcutaneously 8 weeks after tumour cell transplantation. SLNs were extracted, observed using a stereoscopic fluorescence microscope and analysed histologically using haematoxylin and eosin staining, and immunohistochemistry. Lymphoid follicles were found in wild-type swine, and a few aggregated lymphocytes and immature lymphoid follicles were observed in knockout swine. Fluorescence in the lymph nodes indicated metastasis of tumour cells to the lymph nodes. Tumour cells replaced lymph node architectures, showed high-grade nuclear atypia and formed irregular tumour nests. Our model may be useful for the preclinical validation of diagnostic methods and minimally invasive treatment of metastatic cancer.

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Experimental and clinicopathological analysis of HOXB9 in gastric cancer

Kato F., Wada N., Hayashida T., Fukuda K., Nakamura R., Takahashi T., Kawakubo H., Takeuchi H., Kitagawa Y.

Oncology Letters (Oncology Letters) 17 ( 3 ) 3097 - 3102 2019.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 17921074

© 2019, Spandidos Publications. All rights reserved. The association between homeobox (HOX)B9 expression and tumor malignancy was identified recently. It was reported that HOXB9 induced tumor angiogenesis, and associated with poor prognosis in patients with breast and colon cancer. On the other hand, regional lymph nodes are the most common site of tumor spread, and lymph node metastasis is a major prognostic factor in gastric cancer. It was hypothesized that HOXB9 promotes tumor lymphangiogenesis and induces tumor progression, invasion and metastasis in gastric cancer. The aim of the present study was to evaluate the correlation between HOXB9 expression, prognosis and clinicopathologic factors in patients with gastric cancer, and to assess the contribution of HOXB9 expression to tumor cell lymphangiogenesis in vitro. HOXB9 expression was evaluated by immunohistochemistry in resected tumor tissues from 58 patients with gastric cancer, and the association between prognosis and clinicopathologic factors was determined. HOXB9 gene was overexpressed in human gastric cancer TMK-1 cells and the effect of HOXB9 overexpression on the expression of vascular endothelial growth factor (VEGF)-C, VEGF-D and VEGF receptor (R)-3 was determined. It was demonstrated that the depth of tumor invasion, the number of node metastases, lymphatic invasion and vascular invasion were significantly associated with HOXB9 expression. Overall survival was decreased in patients with HOXB9 expression. The mRNA expression of VEGF-D but not of VEGF-C and VEGFR-3 was increased in HOXB9-overexpressing TMK-1 cells compared with control cells. In conclusion, HOXB9 expression was positively correlated with gastric cancer progression and lymphangiogenesis marker expression. HOXB9 may be associated with lymphogenic metastasis.

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Clinicopathologic features of hormone-receptor-positive breast cancer patients with late recurrence

Murata T., Jinno H., Takahashi M., Shimoda M., Hayashida T., Kameyama K., Kitagawa Y.

Breast Journal (Breast Journal) 25 ( 1 ) 9 - 15 2019.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 1075122X

© 2018 Wiley Periodicals, Inc. The number of long-term breast cancer survivors with a risk of late recurrence is increasing. Hormone-receptor-positive patients have greater risks of late recurrence. Although several studies demonstrated that extended adjuvant endocrine therapy reduces the incidence of late recurrence, it remains unclear which hormone-receptor-positive patients have greater risks of late recurrence. Hormone-receptor-positive breast cancer patients were retrospectively selected from the prospective database of primary breast cancer patients treated at Keio University Hospital from January 1989 to December 2003. Late recurrence was defined as initial recurrence after 5 years from the initial surgery. We evaluated the clinicopathologic features of breast cancer patients with late recurrence. At a median follow-up of 10.9 years (range, 5.1-23.8), 371 patients had no recurrence, 90 had early recurrence (within 5 years), and 83 had late recurrence. Multivariate analysis revealed that >4 involved lymph nodes were significant risk factors for late recurrence (P <.001), whereas 1-3 positive nodes were not. Endocrine therapy significantly reduced the incidence of late recurrence (P <.001). After menopause, adjuvant therapy with aromatase inhibitors resulted in longer disease-free survival than tamoxifen (10-year disease-free survival: 97.6% vs 89.7%, P =.0955). High nodal involvement was significantly correlated with late recurrence in hormone-receptor-positive breast cancer patients. Hormone-receptor-positive breast cancer patients who receive adjuvant endocrine therapy with tamoxifen alone might be candidates for extended endocrine therapy.

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Fatty acid β-oxidation-dependent and -independent responses and tumor aggressiveness acquired under mild hypoxia

Wakui M., Kawai K., Mizushima T., Nishime C., Serizawa A., Suemizu H., Asakura K., Yamauchi Y., Hayashida T., Suematsu M., Murata M.

Anticancer Research (Anticancer Research) 39 ( 1 ) 191 - 200 2019.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 02507005

© 2019 International Institute of Anticancer Research. All Rights Reserved. Background/Aim: The present study assessed whether and how tumor cells undergoing hypoxia contribute to disease progression after moving to areas with different oxygen conditions. Materials and Methods: Human colorectal carcinoma HCT116 cells cultured under mild hypoxia were subjected to in vivo experiments using transfer to immunodeficient murine recipients and to in vitro experiments using pharmacological inhibition of fatty acid β-oxidation (FAO). Results: Bone involvement and hepatic metastases were accelerated in transfer models of hypoxically cultured HCT116 cells. Hypoxic HCT116 cells exhibited FAO-dependent glycogen synthesis. FAO-dependent and -independent induction of gene expression also occurred under hypoxia. The distribution of glucose transporter 1 expression compared with heme oxygenase 1 expression in HCT116 cell spheroids seemed consistent with differential dependence of hypoxic expression of these molecules on FAO. Conclusion: These results provide insights into the contribution of hypoxia to tumor progression and the relevance of FAO.

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Salivary metabolomics with alternative decision tree-based machine learning methods for breast cancer discrimination

Murata T., Yanagisawa T., Kurihara T., Kaneko M., Ota S., Enomoto A., Tomita M., Sugimoto M., Sunamura M., Hayashida T., Kitagawa Y., Jinno H.

Breast Cancer Research and Treatment (Breast Cancer Research and Treatment) 177 ( 3 ) 591 - 601 2019

Research paper (scientific journal), Joint Work, Accepted, ISSN 01676806

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Purpose: The aim of this study is to explore new salivary biomarkers to discriminate breast cancer patients from healthy controls. Methods: Saliva samples were collected after 9 h fasting and were immediately stored at − 80 °C. Capillary electrophoresis and liquid chromatography with mass spectrometry were used to quantify hundreds of hydrophilic metabolites. Conventional statistical analyses and artificial intelligence-based methods were used to assess the discrimination abilities of the quantified metabolites. A multiple logistic regression (MLR) model and an alternative decision tree (ADTree)-based machine learning method were used. The generalization abilities of these mathematical models were validated in various computational tests, such as cross-validation and resampling methods. Results: One hundred sixty-six unstimulated saliva samples were collected from 101 patients with invasive carcinoma of the breast (IC), 23 patients with ductal carcinoma in situ (DCIS), and 42 healthy controls (C). Of the 260 quantified metabolites, polyamines were significantly elevated in the saliva of patients with breast cancer. Spermine showed the highest area under the receiver operating characteristic curves [0.766; 95% confidence interval (CI) 0.671–0.840, P < 0.0001] to discriminate IC from C. In addition to spermine, polyamines and their acetylated forms were elevated in IC only. Two hundred each of two-fold, five-fold, and ten-fold cross-validation using different random values were conducted and the MLR model had slightly better accuracy. The ADTree with an ensemble approach showed higher accuracy (0.912; 95% CI 0.838–0.961, P < 0.0001). These prediction models also included spermine as a predictive factor. Conclusions: These data indicated that combinations of salivary metabolomics with the ADTree-based machine learning methods show potential for non-invasive screening of breast cancer.

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Yokoe T., Hayashida T., Kikuchi M., Watanuki R., Nakashoji A., Maeda H., Toyota T., Seki T., Takahashi M., Iwasaki E., Mikami S., Kameyama K., Kitagawa Y.

Clinical Case Reports (Clinical Case Reports) 6 ( 8 ) 1549 - 1553 2018.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 2050-0904

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Antitumor effect of lapatinib and cytotoxic agents by suppression of E2F1 in HER2-positive breast cancer

Matsumoto A., Hayashida T., Takahashi M., Jinno H., Kitagawa Y.

Molecular Medicine Reports (Molecular Medicine Reports) 18 ( 1 ) 958 - 964 2018.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 17912997

Copyright © Spandidos Publications 2017. All rights reserved. The human epidermal growth factor receptor 2 (HER2)-targeting agent, lapatinib, combined with oral fluoropyrimidine capecitabine, has been previously demonstrated to be an effective treatment option for patients with trastuzumab-resistant HER2-positive metastatic breast cancer. To investigate the molecular mechanisms associated with the interactions between lapatinib and capecitabine, the effect of treatment with lapatinib and phosphatidylinositol-4,5-bispho-sphate 3-kinase (PI3K) inhibitors on the expression of E2F transcription factor 1 (E2F1) and thymidylate synthase (TS), which is associated with an increased response to 5-fluorouracil (5-FU)-based chemotherapy, was determined in HER2-positive breast cancer cells. The results of reverse transcription-quantitative polymerase chain reaction demonstrated that administration of lapatinib and PI3K inhibitors decreased the mRNA expression of TS and E2F1, a transcription factor that promotes TS gene expression, in SKBR3 and T47D cell lines. Furthermore, treatment with lapatinib and PI3K inhibitors also suppressed the mRNA expression of ribonucleotide reductase M1 subunit (RRM1), an important determinant of gemcitabine resistance, and DNA topoisomerase II-? (TOP2A), a molecular target of anthracyclines, in SKBR3 and T47D cell lines. Western blot analysis further demonstrated that the phosphorylation of Akt was inhibited by lapatinib, and the results of the MTT assay revealed that the combination of lapatinib with either 5-FU or gemcitabine demonstrated synergistic antitumor effects, whereas a combinatory treatment of lapatinib with epirubicin, a typical anthracycline drug, exhibited antagonistic antitumor effects in HER2-positive breast cancer cells. These results indicate that the synergistic antitumor effects exhibited by combinatory treatment of lapatinib with capecitabine may be induced via the suppression of E2F1-mediated TS expression.

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Phase II trial of eribulin mesylate as a first- or second-line treatment for locally advanced or metastatic breast cancer: A multicenter, single-arm trial

Hayashida T., Jinno H., Mori K., Sato H., Matsui A., Sakurai T., Hattori H., Takayama S., Wada M., Takahashi M., Seki H., Seki T., Nagayama A., Matsumoto A., Kitagawa Y.

BMC Cancer (BMC Cancer) 18 ( 1 ) 701 2018.06

Research paper (scientific journal), Joint Work, Accepted

© 2018 The Author(s). Background: Eribulin mesylate is currently indicated as a sequential monotherapy to be administered after two chemotherapeutic regimens, including anthracycline and taxane treatments, for treatment of metastatic breast cancer. This open-label, multicenter phase II study was designed to evaluate the efficacy and safety of eribulin as a first- or second-line treatment for patients with metastatic breast cancer. Methods: The primary objective was to determine the overall response rate. Secondary objectives were to evaluate progression-free survival and the safety profile. Patients were scheduled to receive eribulin mesylate 1.4 mg/m 2 intravenously on days 1 and 8 of a 21-day cycle. Patients received the study treatment unless disease progression, unacceptable toxicity, or a request to discontinue from the patient and/or investigator eventuated. Results: Between December 2012 and September 2015, 32 patients with metastatic breast cancer were enrolled at 10 participating clinical institutions in Japan, and toxicity and response rates were evaluated. The overall response rate was 43.8% (95% confidence interval [CI] 26.5-61.0). The clinical benefit and tumor control rates were 56.3% (95% CI 39.0-73.5) and 78.1% (95% CI 63.8-92.5), respectively. Median progression-free survival was 8.3 months (95% CI 7.1-9.4). A subgroup analysis did not identify any factors affecting the efficacy of eribulin. The most common adverse events were neutropenia (71.9%), alopecia (68.7%), and peripheral neuropathy (46.9%). As a first- or second-line therapy, eribulin showed sufficient efficacy for metastatic breast cancer compared with taxane and capecitabine treatment in previous clinical trials. The safety profile of eribulin was acceptable. Conclusions: Eribulin may be another option for first-line chemotherapeutic regimens for metastatic breast cancer.

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The updated network meta-analysis of neoadjuvant therapy for HER2-positive breast cancer

Nakashoji A., Hayashida T., Yokoe T., Maeda H., Toyota T., Kikuchi M., Watanuki R., Nagayama A., Seki T., Takahashi M., Abe T., Kitagawa Y.

Cancer Treatment Reviews (Cancer Treatment Reviews) 62 9 - 17 2018.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 03057372

© 2017 Elsevier Ltd Background We previously described a systematic assessment of the neoadjuvant therapies for human epidermal growth factor receptor-2 (HER2) positive breast cancer, using network meta-analysis. Accumulation of new clinical data has compelled us to update the analysis. Methods Randomized trials comparing different anti-HER2 regimens in the neoadjuvant setting were included, and odds ratio for pathologic complete response (pCR) in seven treatment arms were assessed by pooling effect sizes. Direct and indirect comparisons using a Bayesian statistical model were performed. All statistical tests were two-sided. Results A database search identified 993 articles with 13 studies meeting the eligibility criteria, including three new studies with lapatinib (lpnb). In an indirect comparison, dual anti-HER2 agents with CT achieved a better pCR rate than other arms. The credibility intervals of CT + tzmb + lpnb arm were largely reduced compared to our former report, which we added sufficient clinical evidence by this update. Values of surface under the cumulative ranking (SUCRA) suggested that CT + tzmb + pzmb had the highest probability of being the best treatment arm for pCR, widening the difference between the top two dual-HER2 blockade arms compared to our former report. The overall consistency with our first report enhanced the credibility of the results. Conclusion Network meta-analysis using new clinical data firmly establish that combining two anti-HER2 agents with CT is most effective against HER2-positive breast cancer in the neoadjuvant setting. New pzmb related trials are required to fully determine the best neoadjuvant dual-HER2 blockade regimen.

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Actionable gene alterations in an Asian population with triple-negative breast cancer.

Nagahashi M, Ling Y, Hayashida T, Kitagawa Y, Futamura M, Yoshida K, Kuwayama T, Nakamura S, Toshikawa C, Yamauchi H, Yamauchi T, Kaneko K, Kanbayashi C, Sato N, Miyoshi Y, Tsuchida J, Nakajima M, Shimada Y, Ichikawa H, Lyle S, Takabe K, Okuda S, Wakai T

JCO precision oncology 2 2018

Joint Work

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Comprehensive genomic sequencing detects important genetic differences between right-sided and left-sided colorectal cancer.

Shimada Y, Kameyama H, Nagahashi M, Ichikawa H, Muneoka Y, Yagi R, Tajima Y, Okamura T, Nakano M, Sakata J, Kobayashi T, Nogami H, Maruyama S, Takii Y, Hayashida T, Takaishi H, Kitagawa Y, Oki E, Konishi T, Ishida F, Kudo SE, Ring JE, Protopopov A, Lyle S, Ling Y, Okuda S, Ishikawa T, Akazawa K, Takabe K, Wakai T

Oncotarget 8 ( 55 ) 93567 - 93579 2017.11

Research paper (scientific journal), Joint Work, Accepted

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Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma.

Takesue T, Kawakubo H, Hayashida T, Tsutsui M, Miyao K, Fukuda K, Nakamura R, Takahashi T, Wada N, Takeuchi H, Kitagawa Y

Oncology letters 14 ( 4 ) 4220 - 4224 2017.10

Research paper (scientific journal), Joint Work, Accepted, ISSN 1792-1074

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The use of laparoscopic rectopexy to manage rectal prolapse with Pseudo-Meigs' syndrome in a 64-year-old female: a case report.

Kondo T, Tsuruta M, Hasegawa H, Okabayashi K, Shigeta K, Hayashida T, Kitagawa Y

Clinical case reports 5 ( 5 ) 642 - 644 2017.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 2050-0904

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Self-rated cognitive functions following chemotherapy in patients with breast cancer: a 6-month prospective study.

Kitahata R, Nakajima S, Uchida H, Hayashida T, Takahashi M, Nio S, Hirano J, Nagaoka M, Suzuki T, Jinno H, Kitagawa Y, Mimura M

Neuropsychiatric disease and treatment 13 2489 - 2496 2017

Research paper (scientific journal), Joint Work, Accepted, ISSN 1176-6328

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Biological markers of invasive breast cancer.

Matsumoto A, Jinno H, Ando T, Fujii T, Nakamura T, Saito J, Takahashi M, Hayashida T, Kitagawa Y

Japanese journal of clinical oncology 46 ( 2 ) 99 - 105 2016.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 0368-2811

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A randomized controlled study comparing a vessel sealing system with the conventional technique in axillary lymph node dissection for primary breast cancer.

Seki T, Hayashida T, Takahashi M, Jinno H, Kitagawa Y

SpringerPlus 5 ( 1 ) 1004 2016

Research paper (scientific journal), Joint Work, Accepted, ISSN 2193-1801

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Technical feasibility of sentinel lymph node biopsy in patients with ipsilateral breast tumor recurrence and previous axillary surgery.

Matsumoto A, Jinno H, Nakamura T, Saito J, Takahashi M, Hayashida T, Kameyama K, Kitagawa Y

International journal of surgery (London, England) 22 28 - 31 2015.10

Research paper (scientific journal), Joint Work, Accepted, ISSN 1743-9191

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Comprehensive screening of genes resistant to an anticancer drug in esophageal squamous cell carcinoma.

Tsutsui M, Kawakubo H, Hayashida T, Fukuda K, Nakamura R, Takahashi T, Wada N, Saikawa Y, Omori T, Takeuchi H, Kitagawa Y

International journal of oncology 47 ( 3 ) 867 - 74 2015.09

Joint Work, ISSN 1019-6439

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Prognostic implications of receptor discordance between primary and recurrent breast cancer.

Matsumoto A, Jinno H, Murata T, Seki T, Takahashi M, Hayashida T, Kameyama K, Kitagawa Y

International journal of clinical oncology 20 ( 4 ) 701 - 8 2015.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 1341-9625

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Comparison of oncological safety between nipple sparing mastectomy and total mastectomy using propensity score matching.

Seki T, Jinno H, Okabayashi K, Murata T, Matsumoto A, Takahashi M, Hayashida T, Kitagawa Y

Annals of the Royal College of Surgeons of England 97 ( 4 ) 291 - 7 2015.05

Joint Work, ISSN 0035-8843

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Gene transfer of high-mobility group box 1 box-A domain in a rat acute liver failure model.

Tanaka M, Shinoda M, Takayanagi A, Oshima G, Nishiyama R, Fukuda K, Yagi H, Hayashida T, Masugi Y, Suda K, Yamada S, Miyasho T, Hibi T, Abe Y, Kitago M, Obara H, Itano O, Takeuchi H, Sakamoto M, Tanabe M, Maruyama I, Kitagawa Y

The Journal of surgical research 194 ( 2 ) 571 - 80 2015.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 0022-4804

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Response.

Nagayama A, Hayashida T, Jinno H, Takahashi M, Kitagawa Y

Journal of the National Cancer Institute 107 ( 4 ) 2015.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 0027-8874

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単純ヘルペスウイルスの再活性化による口腔内・食道潰瘍を呈した薬剤性過敏症症候群の1例

森本亜里, 舩越建, 福島彩乃, 久保亮治, 海老原全, 林田哲, 真杉洋平, 亀山香織, 永尾圭介

臨床皮膚科 ((株)医学書院) 68 ( 11 ) 873 - 878 2014.10

Research paper (scientific journal), Joint Work, Accepted, ISSN 0021-4973

59歳,女性.乳癌脳転移摘出術後,ゾニサミドを開始した40日後より膝に紅斑が出現し全身に拡大した.初診時,38℃の発熱,顔面の潮紅・腫脹,全身に半米粒大までの紅斑の多発,頬粘膜びらんを認めた.頸部・鼠径部リンパ節腫脹,白血球11,100/μl,好酸球36%,肝酵素はAST 102IU/l,ALT 97IU/lと上昇し,ゾニサミドによる薬剤性過敏症症候群(drug-induced hypersensitivity syndrome:DIHS)と診断し,プレドニゾロン(PSL)60mg/日を開始した.一旦軽快したが発症16日目に発熱,皮疹,口腔内びらんが再燃し,肝酵素値もAST 97IU/ml,ALT 117IU/mlと増悪した.DIHSの2峰目と判断しPSL同量を継続したが口唇・歯肉びらんのみが遷延した.発症25日目に舌潰瘍が多発し,食道潰瘍を認めた.舌・食道の生検組織像で核内封入体を認め,免疫組織染色で単純ヘルペスウイルス(herpes simplex syndrome:HSV)陽性であった.発症30日目ヒトヘルペスウイルス6型(human herpes virus-6:HHV-6)の抗体価上昇およびゾニサミドの薬剤リンパ球刺激試験陽性化がみられた.HSVはHHV-6とともにDIHSの病態に関与するヘルペスウイルス科の1つと考えた.(著者抄録)

Comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis.

Nagayama A, Hayashida T, Jinno H, Takahashi M, Seki T, Matsumoto A, Murata T, Ashrafian H, Athanasiou T, Okabayashi K, Kitagawa Y

Journal of the National Cancer Institute 106 ( 9 ) 2014.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 0027-8874

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Loss of B-cell translocation gene 2 expression in estrogen receptor-positive breast cancer predicts tamoxifen resistance.

Takahashi M, Hayashida T, Okazaki H, Miyao K, Jinno H, Kitagawa Y

Cancer science 105 ( 6 ) 675 - 82 2014.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 1347-9032

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Bevacizumab terminates homeobox B9-induced tumor proliferation by silencing microenvironmental communication.

Hoshino Y, Hayashida T, Hirata A, Takahashi H, Chiba N, Ohmura M, Wakui M, Jinno H, Hasegawa H, Maheswaran S, Suematsu M, Kitagawa Y

Molecular cancer 13 102 2014.05

Research paper (scientific journal), Joint Work, Accepted

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Cetuximab-mediated ADCC activity is correlated with the cell surface expression level of EGFR but not with the KRAS/BRAF mutational status in colorectal cancer.

Seo Y, Ishii Y, Ochiai H, Fukuda K, Akimoto S, Hayashida T, Okabayashi K, Tsuruta M, Hasegawa H, Kitagawa Y

Oncology reports 31 ( 5 ) 2115 - 22 2014.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 1021-335X

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An E2F1-HOXB9 transcriptional circuit is associated with breast cancer progression.

Zhussupova A, Hayashida T, Takahashi M, Miyao K, Okazaki H, Jinno H, Kitagawa Y

PloS one 9 ( 8 ) e105285 2014

Research paper (scientific journal), Joint Work, Accepted

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HMGB1制御による急性肝不全に対する新治療の開発　診療に役立つ治療法の研究

篠田昌宏, 田邉稔, 大島剛, 高野公徳, 西山亮, 田中真之, 林田哲, 八木洋, 阿部雄太, 北郷実, 田中克典, 尾原秀明, 板野理, 須田康一, 竹内裕也, 河地茂行, 北川雄光

日本腹部救急医学会雑誌 ((一社)日本腹部救急医学会) 33 ( 3 ) 535 - 542 2013.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 1340-2242

われわれは,各種病態において炎症性メディエーターとして注目されているHigh-mobility group box 1(HMGB1)に着目し,劇症肝不全に対する新治療の開発を試みている。劇症肝不全患者,薬剤誘導性ラット劇症肝不全モデルにおいて血漿中HMGB1,肝組織中HMGB1は健常群に比較してそれぞれ有意な上昇,低下を認めた。HMGB1に対する特異的中和抗体を薬剤誘導性ラット劇症肝不全モデルに投与したところ著明な病態改善効果を認めた。さらに,HMGB1の阻害剤であるBox Aタンパクの遺伝子導入,リコンビナントトロンボモジュリン投与,HMGB1吸着カラムを用いた体外循環などの有効性を大小の動物モデルで検証した。遺伝子導入,体外循環治療では一定の効果が認められつつあり,診療に役立つ劇症肝不全に対する新治療の開発が期待された。(著者抄録)

Expression of Epidermal Growth Factor Receptor Detected by Cetuximab Indicates Its Efficacy to Inhibit In Vitro and In Vivo Proliferation of Colorectal Cancer Cells.

Shigeta K, Hayashida T, Hoshino Y, Okabayashi K, Endo T, Ishii Y, Hasegawa H, Kitagawa Y

PloS one 8 ( 6 ) e66302 2013

Research paper (scientific journal), Joint Work, Accepted

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Hemoadsorption of high-mobility group box chromosomal protein 1 using a column for large animals.

Nishiyama R, Shinoda M, Tanabe M, Oshima G, Takano K, Miyasho T, Fuchimoto Y, Yamada S, Inoue T, Shimada K, Suda K, Tanaka M, Hayashida T, Yagi H, Kitago M, Obara H, Itano O, Takeuchi H, Kawachi S, Maruyama I, Kitagawa Y

European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes 51 ( 3-4 ) 181 - 90 2013

Joint Work, ISSN 0014-312X

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Correlation between clinical nodal status and sentinel lymph node biopsy false negative rate after neoadjuvant chemotherapy.

Takahashi M, Jinno H, Hayashida T, Sakata M, Asakura K, Kitagawa Y

World journal of surgery 36 ( 12 ) 2847 - 52 2012.12

Research paper (scientific journal), Joint Work, Accepted, ISSN 0364-2313

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[Epithelial-mesenchymal transition and tumor microenvironment propose the seed and soil theory of the present age].

Hayashida T, Jinno H, Kitagawa Y

Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 7 203 - 7 2012.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 0047-1852

[HOXB9 as a novel prognostic factor in breast cancer].

Seki H, Hayashida T, Jinno H, Takahashi M, Kitagawa Y

Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 7 166 - 9 2012.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 0047-1852

HOXB9 expression promoting tumor cell proliferation and angiogenesis is associated with clinical outcomes in breast cancer patients.

Seki H, Hayashida T, Jinno H, Hirose S, Sakata M, Takahashi M, Maheswaran S, Mukai M, Kitagawa Y

Annals of surgical oncology 19 ( 6 ) 1831 - 40 2012.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 1068-9265

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Homeobox B9 induces epithelial-to-mesenchymal transition-associated radioresistance by accelerating DNA damage responses.

Chiba N, Comaills V, Shiotani B, Takahashi F, Shimada T, Tajima K, Winokur D, Hayashida T, Willers H, Brachtel E, Vivanco MD, Haber DA, Zou L, Maheswaran S

Proceedings of the National Academy of Sciences of the United States of America 109 ( 8 ) 2760 - 5 2012.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 0027-8424

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Direct inhibition of the transforming growth factor-β pathway by protein-bound polysaccharide through inactivation of Smad2 signaling.

Ono Y, Hayashida T, Konagai A, Okazaki H, Miyao K, Kawachi S, Tanabe M, Shinoda M, Jinno H, Hasegawa H, Kitajima M, Kitagawa Y

Cancer science 103 ( 2 ) 317 - 24 2012.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 1347-9032

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Differential pathological response to preoperative chemotherapy across breast cancer intrinsic subtypes.

Jinno H, Matsuda S, Hayashida T, Takahashi M, Hirose S, Ikeda T, Kitagawa Y

Chemotherapy 58 ( 5 ) 364 - 70 2012

Research paper (scientific journal), Joint Work, Accepted, ISSN 0009-3157

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Increased plasma levels of high mobility group box 1 in patients with acute liver failure.

Oshima G, Shinoda M, Tanabe M, Ebinuma H, Nishiyama R, Takano K, Yamada S, Miyasho T, Masugi Y, Matsuda S, Suda K, Fukunaga K, Matsubara K, Hibi T, Yagi H, Hayashida T, Yamagishi Y, Obara H, Itano O, Takeuchi H, Kawachi S, Saito H, Hibi T, Maruyama I, Kitagawa Y

European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes 48 ( 3 ) 154 - 62 2012

Joint Work, ISSN 0014-312X

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The influence of donor age on liver regeneration and hepatic progenitor cell populations.

Ono Y, Kawachi S, Hayashida T, Wakui M, Tanabe M, Itano O, Obara H, Shinoda M, Hibi T, Oshima G, Tani N, Mihara K, Kitagawa Y

Surgery 150 ( 2 ) 154 - 61 2011.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 0039-6060

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Primary systemic chemotherapy of breast cancer: indication and predictive factors.

Jinno H, Sakata M, Hayashida T, Takahashi M, Sato T, Seki H, Kitagawa Y

Breast cancer (Tokyo, Japan) 18 ( 2 ) 74 - 9 2011.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 1340-6868

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The integrin alpha(v)beta(3-5) ligand MFG-E8 is a p63/p73 target gene in triple-negative breast cancers but exhibits suppressive functions in ER(+) and erbB2(+) breast cancers.

Yang C, Hayashida T, Forster N, Li C, Shen D, Maheswaran S, Chen L, Anderson KS, Ellisen LW, Sgroi D, Schmidt EV

Cancer research 71 ( 3 ) 937 - 45 2011.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 0008-5472

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Cooperation of cancer stem cell properties and epithelial-mesenchymal transition in the establishment of breast cancer metastasis.

Hayashida T, Jinno H, Kitagawa Y, Kitajima M

Journal of oncology 2011 591427 2011

Research paper (scientific journal), Joint Work, Accepted, ISSN 1687-8450

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Protective effect of high-mobility group box 1 blockade on acute liver failure in rats.

Takano K, Shinoda M, Tanabe M, Miyasho T, Yamada S, Ono S, Masugi Y, Suda K, Fukunaga K, Hayashida T, Hibi T, Obara H, Takeuchi H, Kawachi S, Kawasako K, Okamoto M, Yokota H, Maruyama I, Kitagawa Y

Shock (Augusta, Ga.) 34 ( 6 ) 573 - 9 2010.12

Research paper (scientific journal), Joint Work, Accepted, ISSN 1073-2322

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Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer.

Uchida H, Yamazaki K, Fukuma M, Yamada T, Hayashida T, Hasegawa H, Kitajima M, Kitagawa Y, Sakamoto M

Cancer science 101 ( 7 ) 1731 - 7 2010.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 1347-9032

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[Current strategies of primary therapy for breast cancer].

Hayashida T, Jinno H, Sakata M, Takahashi M, Kitagawa Y

Nihon rinsho. Japanese journal of clinical medicine 68 ( 6 ) 1137 - 42 2010.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 0047-1852

A phase II trial of capecitabine and docetaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) as preoperative treatment in women with stage II/III breast cancer.

Jinno H, Sakata M, Hayashida T, Takahashi M, Mukai M, Ikeda T, Kitagawa Y

Annals of oncology : official journal of the European Society for Medical Oncology 21 ( 6 ) 1262 - 1266 2010.06

Joint Work, ISSN 0923-7534

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HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis.

Hayashida T, Takahashi F, Chiba N, Brachtel E, Takahashi M, Godin-Heymann N, Gross KW, Vivanco Md, Wijendran V, Shioda T, Sgroi D, Donahoe PK, Maheswaran S

Proceedings of the National Academy of Sciences of the United States of America 107 ( 3 ) 1100 - 5 2010.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 0027-8424

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Non-sentinel lymph node status and prognosis of breast cancer patients with micrometastatic sentinel lymph nodes.

Onishi T, Jinno H, Takahashi M, Hayashida T, Sakata M, Nakahara T, Shigematsu N, Mukai M, Kitagawa Y

European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes 45 ( 3-4 ) 344 - 9 2010

Joint Work, ISSN 0014-312X

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Superiority of radioisotope over blue dye for sentinel lymph node detection in breast cancer.

Hayashida T, Jinno H, Sakata M, Takahashi M, Onishi T, Seki H, Sato T, Nakahara T, Shigematsu N, Mukai M, Hibi T, Kitajima M, Kitagawa Y

European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes 44 ( 2 ) 111 - 6 2010

Joint Work, ISSN 0014-312X

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Induction of Foxp3-expressing regulatory T-cells by donor blood transfusion is required for tolerance to rat liver allografts.

Abe Y, Urakami H, Ostanin D, Zibari G, Hayashida T, Kitagawa Y, Grisham MB

PloS one 4 ( 11 ) e7840 2009.11

Research paper (scientific journal), Joint Work, Accepted

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Mullerian-inhibiting substance induces Gro-beta expression in breast cancer cells through a nuclear factor-kappaB-dependent and Smad1-dependent mechanism.

Gupta V, Yeo G, Kawakubo H, Rangnekar V, Ramaswamy P, Hayashida T, MacLaughlin DT, Donahoe PK, Maheswaran S

Cancer research 67 ( 6 ) 2747 - 56 2007.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 0008-5472

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Loss of B-cell translocation gene-2 in estrogen receptor-positive breast carcinoma is associated with tumor grade and overexpression of cyclin d1 protein.

Kawakubo H, Brachtel E, Hayashida T, Yeo G, Kish J, Muzikansky A, Walden PD, Maheswaran S

Cancer research 66 ( 14 ) 7075 - 82 2006.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 0008-5472

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Anti-angiogenic effect of an insertional fusion protein of human basic fibroblast growth factor and ribonuclease-1.

Hayashida T, Ueda M, Aiura K, Tada H, Onizuka M, Seno M, Yamada H, Kitajima M

Protein engineering, design & selection : PEDS 18 ( 7 ) 321 - 7 2005.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 1741-0126

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生体肝移植後ネオーラル使用にて重篤な中枢神経障害をきたした1例

Shibutani Shintarou，Shimazu Motohide，Wakabayashi Gou，Hoshino Ken，Tanabe Minoru，Kawachi Shigeyuki，Yoshida Masashi，Kadomura Tomohisa，Seki Hiroaki，Nagasaki Kazuhito，Fujino Akihiro，Matsui Yoshio，Murayama Takaya，Watanabe Toshihiko，Shimojima Naoki，Hashimoto Takeo，Abe Yuuta，Kaneda Munehisa，Kido Hiromu，Shintani Tsunehiro，Hatou Shin，Hayashida Tetsu，Yagi Hiroshi，Matsumoto Kenji，Morikawa Yasuhide，Kitajima Masaki

今日の移植 15 ( 1 ) 116-117 2002.01

Research paper (scientific journal), Joint Work

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