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Dive into the research topics where Yasuyuki Ohnishi is active.

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Featured researches published by Yasuyuki Ohnishi.


British Journal of Cancer | 1997

Murine P-glycoprotein on stromal vessels mediates multidrug resistance in intracerebral human glioma xenografts.

Y. Takamiya; Yoshiyuki Abe; Y. Tanaka; Atsushi Tsugu; M. Kazuno; Y Oshika; K. Maruo; Yasuyuki Ohnishi; Sato O; Hitoshi Yamazaki; Hiroshi Kijima; Yoshito Ueyama; Norikazu Tamaoki; Masato Nakamura

Human glioma usually shows intrinsic multidrug resistance because of the blood-brain barrier (BBB), in which membrane-associated P-glycoprotein (P-gp), encoded by the human multidrug resistance gene MDR1, plays a role. We studied drug sensitivity to vincristine (VCR), doxorubicin (DOX) and nimustine (ACNU) in both intracerebrally and subcutaneously xenotransplanted human glioma. We examined the levels of MDR1 and murine mdr3 gene expression in the xenografts by reverse transcriptase polymerase chain reaction and the localization of P-gp by immunohistochemistry. Six of seven subcutaneously transplanted xenografts (scX) were sensitive to the above three drugs. In contrast, all three intracerebrally transplanted human glioma xenografts (icX) were resistant to P-gp-mediated drugs VCR and DOX, but were sensitive to the non-P-gp-mediated drug ACNU. Neither icX nor scX showed any MDR1 expression. Intracerebrally transplanted human glioma xenografts showed an increased level of murine mdr3 gene expression, whereas scX showed only faint expression. The localization of P-gp was limited to the stromal vessels in icX by immunohistochemistry, whereas scX expressed no P-gp. Our findings suggest that the P-gp expressed on the stromal vessels in icX is a major contributing factor to multidrug resistance in human glioma in vivo.


Oncology | 1996

In vitro-in vivo correlation in anticancer drug sensitivity test using AUC-based concentrations and collagen gel droplet-embedded culture.

Makoto Inaba; Tazuko Tashiro; Shigeo Sato; Yasuyuki Ohnishi; Keizo Tanisaka; Hisayuki Kobayashi; Masahiro Koezuka

To improve the ability of an in vitro drug sensitivity test to predict in vivo effects, we applied a drug concentration that was pharmacokinetically equivalent to plasma levels and collagen gel droplet-embedded culture with a high cloning efficiency. We reported that the cell-killing effect of cell cycle phase-nonspecific drugs such as mitomycin C, cisplatin and Adriamycin depends on the area under the drug concentration-time curve (AUC). The plasma AUC values of these drugs were estimated after an injection into nude mice at the maximal tolerated doses (MTD). Tumor cells isolated from human tumor xenografts implanted into nude mice and cultured in collagen gel droplets were exposed to drugs under conditions that can reproduce the plasma AUC in vitro. The in vitro sensitivity to a drug was compared with the in vivo response of the same tumor treated with the MTD of the drug. When the criterion of sensitivity was taken as 50% or less of the growth inhibition (growth rate of treated group/that of control group, T/C), the correlation between the in vitro and in vivo growth inhibition of all 3 drugs tested was relatively high (86% of the true-positive rate, 82% of the true-negative rate and 83% of the correlation rate).


British Journal of Cancer | 1996

P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo.

Yoshiyuki Abe; Yasuyuki Ohnishi; Masumi Yoshimura; Eiichiro Ota; Yuichi Ozeki; Y Oshika; Tetsuji Tokunaga; Hitoshi Yamazaki; Ueyema Y; Toshiro Ogata; Norikazu Tamaoki; Masato Nakamura

We examined whether the increased expression of P-glycoprotein (P-gp) encoded by the human multidrug resistance gene MDR1 is related to the acquired multidrug resistance of lung cancer in vivo. We estimated the chemosensitivity of lung cancer xenografts (LC-6, adenocarcinoma; Lu-24, small-cell cancer) by calculation of relative tumour growth (T/C%, treated/control) in vivo, based on statistical significance determined by the Mann-Whitney U test (P < 0.01, one-sided). MDR1 gene expression levels were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) assay. P-gp production and P-gp localisation were examined by Western blotting and by immunohistochemical analysis respectively. LC-6 and Lu-24 were initially sensitive to both vincristine (VCR, 1.6 mg kg-1: LC-6, 45%; Lu-24, 39%) and doxorubicin (DOX, 12 mg kg-1: LC-6, 26%; Lu-24, 27%) in vivo. VCR-resistant variants (LC-6R, 66% and Lu-24R, 68%) selected with VCR (0.4 mg kg-1, x 9) significantly acquired cross-resistance to DOX (LC-6R, 55% and Lu-24R, 55% respectively). RT-PCR assay showed increased levels of MDR1 expression in LC-6R and Lu-24R with stable MDR1 expression levels. P-gp expression levels were elevated, and the percentage of P-gp-positive tumour cells increased in both LC-6R and Lu-24R. These results suggest that P-gp/MDR1 overexpression is related to acquired multidrug resistance in lung cancer in vivo.


Cancer Chemotherapy and Pharmacology | 1997

Pharmacokinetics of CPT-11 in rhesus monkeys

Makoto Inaba; Yasuyuki Ohnishi; Hajime Ishii; Yoshikuni Tanioka; Ysaushi Yoshida; Kenichi Sudoh; Hideo Hakusui; Naomi Mizuno; Kiyomi Ito; Yuichi Sugiyama

Purpose: To examine the pharmacokinetic relationships between humans and monkeys, we studied the disposition of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), in rhesus monkeys. Methods: CPT-11 was administered to a total of six monkeys at doses of 3, 7, 15 and 25 mg/kg by intravenous infusion for 10 min and plasma concentrations and pharmacokinetic parameters of CPT-11 determined. Results: Maximum plasma concentrations at 25 mg/kg reached around 10 000 ng/ml, and dropped to 500 ng/ml in 8 h. Plasma concentrations of SN-38 remained between 2 and 10 ng/ml. Mean values of systemic clearance, mean residence time and distribution volume at steady state, the major pharmacokinetic parameters for CPT-11, were 13.3 (ml/min per kg), 192 (min) and 2553 (ml/kg), respectively. The initial plasma concentration ratio of lactone to total CPT-11, 76%, declined to about 20% within 75 min, and the final ratio was about 40% at 8 h; the initial ratio of SN-38 was 72%, dropped to 34% within 70 min and finally recovered to 55% at 8 h. Conclusion: Comparison with human data revealed that systemic clearances of CPT-11 and the maximum AUC of SN-38 were not as different between humans and monkeys as between humans and mice, but the metabolic conversion of CPT-11 into SN-38 in monkeys was significantly lower than in humans.


Apmis | 1997

A xenograft line of human teratocarcinoma established by serial transplantation in severe combined immunodeficient (SCID) mice

Yoshiyuki Abe; Y Oshika; Yasuyuki Ohnishi; Ryuji Suto; Tetsuji Tokunaga; Hitoshi Yamazaki; Hiroshi Kijima; Nobuyoshi Hiraoka; Yoshito Ueyama; Norikazu Tamaoki; Masato Nakamura

We established a xenograft line of human teratocarcinoma (TC‐1) and characterized the pluripotency of differentiation of the neoplastic cells. A teratocarcinoma specimen obtained from a primary mediastinal lesion (22‐year‐old male patient) was inoculated subcutaneously into severe combined immunodeficient (SCID) mice. The carcinoma formed tumors in the mice. We established a xenograft line by serial passage of the tumor in vivo. The primary tumor was composed of papillary and pseudoglandular nests of highly atypical epithelial cells with foci of glomeruloid structures. The metastatic cells showed apparent production of mucin and differentiation to striated muscle. The xenograft line TC‐1 retained the basic histopathological features seen in the primary and metastatic cells. The xenograft line showed focal differentiation to cartilage through serial passages. Immunohistochemical studies with anti‐α‐fetoprotein (AFP) demonstrated positive immunoreactivity on the TC‐1 cells. Serum AFP levels were also elevated in the TC‐1‐bearing SCID mice. The human teratocarcinoma xenograft line TC‐1 will be useful for studying the differentiation mechanism in human totipotent stem cells.


Journal of the National Cancer Institute | 1998

Inhibition of Tumor Growth by Ribozyme-Mediated Suppression of Aberrant Epidermal Growth Factor Receptor Gene Expression

Hitoshi Yamazaki; Hiroshi Kijima; Yoshiyuki Abe; Y Oshika; T Tsuchida; Tetsuji Tokunaga; Norikazu Tamaoki; Masato Nakamura; Atsushi Tsugu; Yasuyuki Ohnishi; Yoshito Ueyama


Cancer Research | 1998

Identification of Two Common Regions of Allelic Loss in Chromosome Arm 12q in Human Pancreatic Cancer

Mitsuhiro Kimura; Toru Furukawa; Tadayoshi Abe; Toshimasa Yatsuoka; Emile M. Youssef; Tadaaki Yokoyama; Hong Ouyang; Yasuyuki Ohnishi; Makoto Sunamura; Masao Kobari; Seiki Matsuno; Akira Horii


Journal of the National Cancer Institute | 1998

Is Xenotransplantability of Human Colon Cancers in SCID Mice Affected by Angiogenic Factors

Tetsuji Tokunaga; Masato Nakamura; Y Oshika; Yoshito Ueyama; Yasuyuki Ohnishi


Oncology Reports | 1998

A human lung cancer xenograft producing granulocyte-colony stimulating factor and parathyroid hormone-related protein.

Y Oshika; Masato Nakamura; Hiroyuki Hatanaka; Yoshiyuki Abe; Tetsuji Tokunaga; Yasuyuki Ohnishi; Hiroshi Kijima; Hitoshi Yamazaki; Norikazu Tamaoki; Yoshito Ueyama


Anticancer Research | 1997

Localization of aberrant messenger RNA of epidermal growth factor receptor (EGFR) in malignant glioma.

Atsushi Tsugu; Hiroshi Kijima; Hitoshi Yamazaki; Yasuyuki Ohnishi; Y. Takamiya; Yoshiyuki Abe; Yoshito Ueyama; Sato O; Norikazu Tamaoki; Masato Nakamura

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Yoshito Ueyama

Central Institute for Experimental Animals

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Makoto Inaba

Japanese Foundation for Cancer Research

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