Faculty Profiles - FUJIWARA Toshiyoshi

Takahito Yagi, Daisuke Nobuoka, Susumu Shinoura, Yuzo Umeda, Daisuke Sato, Ryuichi Yoshida, Masashi Utsumi, Tomokazu Fuji, Hiroshi Sadamori, Toshiyoshi Fujiwara

HEPATOLOGY RESEARCH 44 ( 3 ) 358 - 363 2014.3

Language：English Publisher：WILEY-BLACKWELL

Establishment of a preferential liver allocation rule for simultaneous liver and kidney transplantation (SLK) and revisions of laws regarding organ transplants from deceased donors have paved the way for SLK in Japan. Very few cases of SLK have been attempted in Japan, and no such recipients have survived for longer than 40 days. The present report describes a case of a 50-year-old woman who had undergone living donor liver transplantation at the age of 38 years for management of post-partum liver failure. After the first transplant surgery, she developed hepatic vein stenosis and severe hypersplenism requiring splenectomy. She was then initiated on hemodialysis (HD) due to the deterioration of renal function after insertion of a hepatic vein stent. She was listed as a candidate for SLK in 2011 because she required frequent plasma exchange for hepatic coma. When her Model for End-stage Liver Disease score reached 46, the new liver was donated 46 days after registration. The reduced trisegment liver and the kidney grafts were simultaneously transplanted under veno-venous bypass and intraoperative HD. The hepatic artery was reconstructed prior to portal reconstruction in order to shorten anhepatic time. Although she developed subcapsular bleeding caused by hepatic contusion on the next day, subsequent hemostasis was obtained by transcatheter embolization. Thereafter, her recovery was uneventful, except for mild rejection and renal tubular acidosis of the kidney graft. This case highlights the need to establish Japanese criteria for SLK.

DOI： 10.1111/hepr.12122

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Invading cancer cells are predominantly in G(0)/G(1) resulting in chemoresistance demonstrated by real-time FUCCI imaging

Shuya Yano, Shinji Miwa, Sumiyuki Mii, Yukihiko Hiroshima, Fuminari Uehara, Mako Yamamoto, Hiroyuki Kishimoto, Hiroshi Tazawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert M. Hoffman

CELL CYCLE 13 ( 6 ) 953 - 960 2014.3

Language：English Publisher：LANDES BIOSCIENCE

Invasive cancer cells are a critical target in order to prevent metastasis. In the present report, we demonstrate real-time visualization of cell cycle kinetics of invading cancer cells in 3-dimensional (3D) Gelfoam (R) histoculture, which is in vivo-like. A fluorescence ubiquitination cell cycle indicator (FUCCI) whereby G(0)/G(1) cells express a red fluorescent protein and S/G(2)/M cells express a green fluorescent protein was used to determine the cell cycle position of invading and non-invading cells. With FUCCI 3D confocal imaging, we observed that cancer cells in G(0)/G(1) phase in Gelfoam (R) histoculture migrated more rapidly and further than cancer cells in S/G(2)/M phases. Cancer cells ceased migrating when they entered S/G(2)/M phases and restarted migrating after cell division when the cells re-entered G(0)/G(1). Migrating cancer cells also were resistant to cytotoxic chemotherapy, since they were preponderantly in G(0)/G(1), where cytotoxic chemotherapy is not effective. The results of the present report suggest that novel therapy targeting G(0)/G(1) cancer cells should be developed to prevent metastasis.

DOI： 10.4161/cc.27818

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Management Of Peritoneal Effusion by Sealing with a Self-Assembling Nanofiber Polypeptide Following Pelvic Surgery

Yoshitaka Kondo, Takeshi Nagasaka, Satoru Kobayashi, Naoya Kobayashi, Toshiyoshi Fujiwara

HEPATO-GASTROENTEROLOGY 61 ( 130 ) 349 - 353 2014.3

Language：English Publisher：H G E UPDATE MEDICAL PUBLISHING S A

Background/Aims: PuraMatrix is a synthetic material consisting of 16-amino acid peptides that self-assemble into nanofibers, previously used as a scaffold for functional cell cultures. We conducted a clinical study to determine the safety and sealing properties of PuraMatrix in post-operative lymphorrhea following pelvic surgery in humans. Methodology: A total of 20 patients who underwent rectal cancer resection were analyzed. The study group (n = 10) consisted of patients who received PuraMatrix, matched with a control group (n = 10) of patients operated on conventionally. Results: During the 2 to 3 month follow-up period, there were no abnormal findings or adverse events in any the patients who received PuraMatrix. We found that the patients who received PuraMatrix had significantly reduced post-operative drainage volumes compared with the patients in the control group. Conclusions: PuraMatrix is a safe and effective bio-compatible sealing material for the management of post-operative peritoneal effusion following pelvic surgery.

DOI： 10.5754/hge121000

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First successful case of simultaneous liver and kidney transplantation for patients with chronic liver and renal failure in Japan

Takahito Yagi, Daisuke Nobuoka, Susumu Shinoura, Yuzo Umeda, Daisuke Sato, Ryuichi Yoshida, Masashi Utsumi, Tomokazu Fuji, Hiroshi Sadamori, Toshiyoshi Fujiwara

HEPATOLOGY RESEARCH 44 ( 3 ) 358 - 363 2014.3

Language：English Publisher：WILEY-BLACKWELL

DOI： 10.1111/hepr.12122

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Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers

Mitsuya Itoh, Takayuki Iwamoto, Junji Matsuoka, Tomohiro Nogami, Takayuki Motoki, Tadahiko Shien, Naruto Taira, Naoki Niikura, Naoki Hayashi, Shoichiro Ohtani, Kenji Higaki, Toshiyoshi Fujiwara, Hiroyoshi Doihara, W. Fraser Symmans, Lajos Pusztai

BREAST CANCER RESEARCH AND TREATMENT 143 ( 2 ) 403 - 409 2014.1

Language：English Publisher：SPRINGER

We examined estrogen receptor (ER) mRNA expression and molecular subtypes in stage I-III breast cancers that are progesterone receptor (PR) positive but ER and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization. The ER, PR, and HER2 status was determined by IHC as part of routine clinical assessment (N = 501). Gene expression profiling was done with the Affymetrix U133A gene chip. We compared expressions of ESR1 and MKI67 mRNA, distribution of molecular subtypes by the PAM50 classifier, the sensitivity to endocrine therapy index, and the DLDA30 chemotherapy response predictor signature among ER/PR-positive (n = 223), ER-positive/PR-negative (<Emphasis Type="ItalicUnderline">n = 73), ER-negative/PR-positive (n = 20), and triple-negative (n = 185) cancers. All patients received neoadjuvant chemotherapy with an anthracycline and taxane and had adjuvant endocrine therapy only if ER or PR > 10 % positive. ESR1 expression was high in 25 % of ER-negative/PR-positive, in 79 % of ER-positive/PR-negative, in 96 % of ER/PR-positive, and in 12 % of triple-negative cancers by IHC. The average MKI67 expression was significantly higher in the ER-negative/PR-positive and triple-negative cohorts. Among the ER-negative/PR-positive patients, 15 % were luminal A, 5 % were Luminal B, and 65 % were basal like. The relapse-free survival rate of ER-negative/PR-positive patients was equivalent to ER-positive cancers and better than the triple-negative cohort. Only 20-25 % of the ER-negative/PR-positive tumors show molecular features of ER-positive cancers. In this rare subset of patients (i) a second RNA-based assessment may help identifying the minority of ESR1 mRNA-positive, luminal-type cancers and (ii) the safest clinical approach may be to consider both adjuvant endocrine and chemotherapy.

DOI： 10.1007/s10549-013-2763-z

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腺様嚢胞癌細胞株に対するテロメラーゼ特異的腫瘍融解ウイルスと放射線照射併用による抗腫瘍効果の検討

佐藤大典, 栗原祐史, 加藤光佑, 近藤誠二, 代田達夫, 浦田泰生, 藤原俊義, 新谷悟

日本口腔科学会雑誌 63 ( 1 ) 94 - 94 2014.1

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