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Dive into the research topics where Toshiro Kusakabe is active.

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Featured researches published by Toshiro Kusakabe.


Human Gene Therapy | 2000

GST-π gene-transduced hematopoietic progenitor cell transplantation overcomes the bone marrow toxicity of cyclophosphamide in mice

Takuya Matsunaga; Sumio Sakamaki; Takashi Kuga; Hiroyuki Kuroda; Toshiro Kusakabe; Takehide Akiyama; Yuichi Konuma; Yasuo Hirayama; Masayoshi Kobune; Junji Kato; Katsunori Sasaki; Katsuhisa Kogawa; Ryuzo Koyama; Yoshiro Niitsu

Autologous transplantation of bone marrow cells (BMCs) transduced with the multidrug resistance 1 (MDR1) gene or dihydrofolate reductase (DHFR) gene has already been applied in clinical chemoprotection trials. However, anticancer drugs frequently used in high-dose chemotherapy (HDC), such as alkylating agents, are not relevant to MDR1 or DHFR gene products. In this context, we have previously reported that glutathione S-transferase-pi (GST-pi) gene-transduced human CD34(+) cells showed resistance in vitro against 4-hydroperoxicyclophosphamide, an active form of cyclophosphamide (CY). In the present study, a subsequent attempt was made in a murine model to evaluate the effectiveness of transplantation of GST-pi-transduced BMCs to protect bone marrow against high-dose CY. The gene transfection was carried out retrovirally, employing a recombinant fibronectin fragment. Transfection efficiency into CFU-GM was 30%. After the transplantation, recipient mice (GST-pi mice) received three sequential courses of high-dose CY. As the chemotherapy courses advanced, both shortening of recovery period from WBC nadir and shallowing of WBC nadir were observed. In contrast to the fact that three of seven control mice died, possibly due to chemotoxicity, all seven GST-pi mice were alive after the third course, at which point the vector GST-pi gene was detected in 50% of CFU-GM derived from their BMCs and peripheral blood mononuclear cells. When BMCs obtained from these seven mice were retransplanted into secondary recipient mice, 20% of CFU-GM from BMCs showed positive signals for vector GST-pi DNA after 6 months. These data indicate that the GST-pi gene can confer resistance to bone marrow against CY by being transduced into long-term repopulating cells.


International Journal of Hematology | 2001

Long-term survival and late-onset complications of cancer patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation

Kyuhei Kohda; Sumio Sakamaki; Takuya Matsunaga; Takashi Kuga; Akihito Fujimi; Yuichi Konuma; Toshiro Kusakabe; Katsuhisa Kogawa; Takehide Akiyama; Kazuhiko Koike; Yasuo Hirayama; Yutaka Sasagawa; Syuichi Nojiri; Yasuji Hirata; Takuji Nishisato; Yoshiro Niitsu

The antitumor effect of high-dose chemotherapy (HDC) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) is considered superior to that of conventional chemotherapy. However, the long-term benefits of this strategy in Japan remain unclear.Therefore, in this study, 109 cancer patients enrolled between 1989 and 1999 were treated with HDC and auto-PBSCT. Patients were evaluated for long-term survival and late-onset complications, including secondary malignancy. The mean number of CD34+ cells harvested per apheresis was larger in the group receiving high-dose cytosine arabinoside or high-dose etoposide plus granulocyte colony-stimulating factor (G-CSF) than in the group receiving conventional chemotherapy plus G-CSF. The 5-year overall survival rates for non-Hodgkin’s lymphoma patients in first complete remission (CR) (83.2%), second or subsequent CR (74.1%), or first partial remission (PR) (66.7%) at the time of transplantation were significantly higher than those with no remission (35.7%) at the time of transplantation (first CR,P < .05; second or subsequent CR,P < .05; first PR,P < .05). The 5-year overall survival (OS) rates for breast cancer was 40.8%, and the disease-free survival rate was extremely low (8.8%). The 5-year OS rates for chemotherapy-sensitive and chemotherapy-resistant diseases at the time of transplantation were 32.7% and 35.7%, respectively, a difference that was not considered significant. The 5-year OS for germ cell tumor was 80.0%, and the disease-free survival rate was 77.9%. The rate of therapy-related death was 8.2%. The occurrence rate of secondary malignancy was 0.9%. Late-onset complications were observed in 4 cases (glomerulonephritis, interstitial pneumonitis, ulcerative colitis, and acute myelogenous leukemia). At 3.7%, the occurrence rate was not very high, but most complications of auto-PBSCT were life threatening and interfered with patients’ quality of life. A careful follow-up is required for at least 2 years after transplantation, because the mean occurrence time of late-onset complications is 16.7 months posttransplantation.


Journal of Clinical Oncology | 2014

Effect of duloxetine on chemotherapy-induced painful peripheral neuropathy.

Yasuo Hirayama; Takeshi Terui; Kazuhiko Koike; Toshiro Kusakabe; Hiroto Horiguthi; Kunihiko Ishitani

181 Background: Approximately 20% to 40% of patients with cancer who receive neurotoxic chemotherapy will develop painful chemotherapy-induced peripheral neuropathy. Smith et. al firstly reported that duloxetine was effective on above neuropathy after taxanes and platinums (JAMA 2013), so we planed to evaluate the duloxetine effect in Japanese patients after above drugs and more expanding drugs include vinca alkaloids and bortezomib. METHODS Patients were randomized to receive either duloxetine followed by vitamin(V)B12 or VB12 by duloxetine. The initial treatment consisted of 20 mg of duloxetine or 1.5g VB12 for the first week and 40mg of duloxetine or VB12 daily for 3 additional weeks (an open label, randomized, crossover). Dose reduction by the adverse effects was permitted. The primary hypothesis was that duloxetine would be more effective than VB12 in decreasing chemotherapy-induced peripheral neuropathic pain. Numbness and Pain severity were assessed weekly using visual analogue scale (VAS). This research was approved by the Research Ethics Committee of Higashi Sapporo Hospital and University Hospital Medical Information Network (UMIN) Center in Japan.Thirty-four cases (Breast cancer: taxanes 2, gastric cancer: taxane 5, colon cancer: oxaliplatin 6, Malignant lymphoma: vincristine 13, multiple myeloma: bortezomib 8) were made an entry in our institution. Five cases dropped out because of the adverse effect with sleepy and general malaise. RESULTS Obvious improvements of VAS scores of numbness and pain were observed in duloxetine group. Significant differences of delta VAS (pre VAS scale - 4 weeks VAS after drug administration) were observed between duloxetine group and VB12 group in the aspect of numbness (p=0.02) and pain (p=0.03). CONCLUSIONS Among patients with painful chemotherapy-induced peripheral neuropathy, the use of duloxetine compared with VB12 for 4 weeks resulted in a reduction in numbness and pain, but there are many cases with drop out by the adverse effects. CLINICAL TRIAL INFORMATION 000011554.


American Journal of Hospice and Palliative Medicine | 2014

Recent Advances in Palliative Cancer Care at a Regional Hospital in Japan

Takeshi Terui; Kazuhiko Koike; Yasuo Hirayama; Toshiro Kusakabe; Kaoru Ono; Hiroyoshi Mihara; Kenji Kobayashi; Yuji Takahashi; Nobuhisa Nakajima; Junji Kato; Kunihiko Ishitani

More than 30 years have passed since the introduction of the concept of palliative care in cancer care in Japan. However, the majority of the estimated three million cancer patients in Japan do not receive palliative care. Higashi Sapporo Hospital was established in 1983 as a hospital specialized in cancer care. The palliative care unit of our hospital currently consists of 58 beds. Our hospital is one of the largest hospitals in Japan in terms of the number of palliative care beds. On admission to our hospital, all patients are evaluated for palliative care by a multi-disciplinary team and some patients who undergo anticancer therapy receive palliative care when necessary. There are about 65 patients on average (28.3%) who are receiving only palliative care. In 2011, 793 patients died of cancer while admitted at our hospital. This number of cancer deaths accounted for 15% of the 5,324 cancer deaths in Sapporo City in the same year. Our hospital has played an active role according to the philosophy that “palliative cancer care is part of cancer medical care”. We here report the current status of the contribution of our hospital to overcoming problems in palliative care and cancer care in Japan.   


American Journal of Hospice and Palliative Medicine | 2014

A Survey of Patients Who Were Referred to Our Palliative Care Division From Other Hospitals and Appeared to Have Obvious Indications for Cancer Chemotherapies

Yasuo Hirayama; Takeshi Terui; Toshiro Kusakabe; Kazuhiko Koike; Kaoru Ono; Junji Kato; Kunihiko Ishitani

Higashi Sapporo Hospital is a cancer-specific hospital with palliative care doctors and certified oncologists. During case conferences held twice a week, we routinely evaluate the referred patients. In our case conferences, we selected patients who were referred to our palliative care division from other hospitals, with possible indications for cancer chemotherapies. We reviewed a total of 1215 patients who were referred to our palliative care division. We identified 18 cases as having indications for cancer chemotherapies. Among them, we identified 4 cases as having indications for standard cancer chemotherapies. All 4 patients tolerated the therapies well, responded to chemotherapy, and survived for more than 1 year. Conferences in which oncologists and palliative care doctors can discuss cases frequently and intimately are thought to be important.


Blood | 1998

Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells

Yasuo Hirayama; Sumio Sakamaki; Takuya Matsunaga; Takashi Kuga; Hiroyuki Kuroda; Toshiro Kusakabe; Katsunori Sasaki; Koshi Fujikawa; Junji Kato; Katsuhisa Kogawa; Ryuzo Koyama; Yoshiro Niitsu


Blood | 1999

Transforming Growth Factor-β1 (TGF-β1) Induces Thrombopoietin From Bone Marrow Stromal Cells, Which Stimulates the Expression of TGF-β Receptor on Megakaryocytes and, in Turn, Renders Them Susceptible to Suppression by TGF-β Itself With High Specificity

Sumio Sakamaki; Yasuo Hirayama; Takuya Matsunaga; Hiroyuki Kuroda; Toshiro Kusakabe; Takehide Akiyama; Yuichi Konuma; Katsunori Sasaki; Naoki Tsuji; Tetsuro Okamoto; Masayoshi Kobune; Katsuhisa Kogawa; Junji Kato; Rishu Takimoto; Ryuzo Koyama; Yoshiro Niitsu


Human Gene Therapy | 1997

Fibronectin Fragment-Facilitated Retroviral Transfer of the Glutathione-S-Transferase π Gene into CD34+ Cells to Protect Them Against Alkylating Agents

Takashi Kuga; Sumio Sakamaki; Takuya Matsunaga; Yasuo Hirayama; Hiroyuki Kuroda; Yasuo Takahashi; Toshiro Kusakabe; Ikunoshin Kato; Yoshiro Niitsu


Blood | 2001

Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603

Yue Lu; Sumio Sakamaki; Hiroyuki Kuroda; Toshiro Kusakabe; Yuichi Konuma; Takehide Akiyama; Akihito Fujimi; Naofumi Takemoto; Kyokusen Nishiie; Takuya Matsunaga; Yasuo Hirayama; Junji Kato; Shinichiro Kon; Katsuhisa Kogawa; Yoshiro Niitsu


International Journal of Clinical Oncology | 2015

Effect of duloxetine in Japanese patients with chemotherapy-induced peripheral neuropathy: a pilot randomized trial

Yasuo Hirayama; Kunihiko Ishitani; Yasushi Sato; Satoshi Iyama; Kohichi Takada; Kazuyuki Murase; Kuroda H; Yasuhiro Nagamachi; Yuichi Konuma; Akihito Fujimi; Tamotsu Sagawa; Kaoru Ono; Hiroto Horiguchi; Takeshi Terui; Kazuhiko Koike; Toshiro Kusakabe; Tsutomu Sato; Rishu Takimoto; Masayoshi Kobune; Junji Kato

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Yasuo Hirayama

Sapporo Medical University

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Junji Kato

Sapporo Medical University

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Sumio Sakamaki

Sapporo Medical University

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Hiroyuki Kuroda

Sapporo Medical University

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Takehide Akiyama

Sapporo Medical University

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Yoshiro Niitsu

Albert Einstein College of Medicine

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Katsuhisa Kogawa

Sapporo Medical University

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Takeshi Terui

Sapporo Medical University

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