Biomedical subjects

Masakazu Toi

Publications and source records attributed to Masakazu Toi.

79 records · Page 5Linked to original sources

PubMedDate not supplied

Impact of selective Glisson transection on survival of hepatocellular carcinoma.

BACKGROUND/AIMS: The aim of this study is to assess whether selective transection of tumor-bearing portal pedicle before dissection of the liver parenchyma in hepatectomy for hepatocellular carcinoma can prevent intraoperative spread of the tumor and can lead to the prolongation of postoperative survival. METHODOLOGY: Survival for 159 patients who underwent hepatectomies with selective portal transection by Glissonean pedicle transection method was retrospectively compared with that of 100 patients who underwent hepatectomies with Pringle maneuver. According to the number of recurrent tumors, intrahepatic recurrence was divided into two types: nodular type of 3 or less, diffuse type of 4 or more. RESULTS: The 5-year survival for the patients who underwent hepatectomies with Glissonean pedicle transection method was significantly higher than that with Pringle maneuver (64.7% vs. 36.4%, p < 0.0001, log-rank test). The diffuse type recurrence, which occurred early and resulted in the unfavorable prognosis compared with the nodular type, was significantly reduced in patients treated with Glissonean pedicle transection method compared with those with Pringle maneuver (p = 0.0013). Multivariate analyses demonstrated that Glissonean pedicle transection method was a potent independent prognostic indicator for survival. CONCLUSIONS: Glissonean pedicle transection method prevented intraoperative metastasis and significantly improved the postoperative survival in patients with hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Immunohistochemical analysis of estrone sulfatase and aromatase in human breast cancer tissues.

We examined, by immunohistochemical analysis, the expression of aromatase and estrone sulfatase (E1-STS) which are the two major enzymes involved in in situ estrogen synthesis in breast cancer tissue. In the 83 cases examined, E1-STS, which hydrolyses estrone sulfate (E1S) to estrone (E1), was dominantly detected in tumor cells in 43 (59.0%) cases. Aromatase, which converts androgens to estrogens, was dominantly detected in stromal cells of the tumor. It was detected in 39 (47.0%) of the 83 cases. There was no significant correlation between the expression of these two enzymes and clinicopathological factors. We found a tendency for a correlation between aromatase expression and E1-STS expression in breast tumor (p=0.075). In terms of the possible use of these enzymes as prognostic indicators, patients who had aromatase in their tumor showed longer relapse-free survival than those lacking aromatase (p=0.045). Significant correlations between the expression of aromatase and the angiogenesis regulators, vascular endothelial growth factor and thymidine phosphorylase, were found (p=0.047 and p=0.046, respectively), though the presence of aromatase did not correlate with intratumoral microvessel density. This may indicate that aromatase is involved in vascular permeability and recruitment of endothelial cells rather than neovascularization. It may be useful to study the expression of aromatase and E1-STS using immunocytochemical analysis for understanding the tumor characteristics in breast cancer.

Adult↗

PubMedDate not supplied

Mutation analysis of copper-transporting P-type adenosine triphosphatase (ATP7B) in human solid carcinomas.

A major obstacle in the treatment of human solid carcinomas is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphatase (ATP7B) has been reported to be associated with cisplatin resistance in vitro. ATP7B is overexpressed in human solid carcinomas such as breast, gastric and oral squamous cell carcinomas. ATP7B expression has an influential effect on some subsets of patients with cisplatin-treated carcinomas. ATP7B mutation is well-known as a cause of Wilson's disease. In addition, the six copper-binding domain and ATP-binding domain of ATP7B are important for the transportation of metals. Therefore, we performed the mutation analysis at the six copper-binding domain and ATP-binding domain of ATP7B. No mutation at the six copper-binding domain and ATP-binding domain was observed in breast, gastric and oral squameous cell carcinomas. These results indicate that the analysis of the ATP7B gene and/or protein will be helpful for the choice of chemotherapy in patients with human solid carcinomas.

Adenosine Triphosphatases↗

PubMedDate not supplied

Survival benefit of KRN7000 immune therapy in combination with TNP470 in hamster liver metastasis model of pancreatic cancer.

Pancreatic cancer is a solid malignancy with the poor prognosis largely due to frequent and lethal liver metastases. The combination of immunotherapy and anti-angiogenesis therapy might be a hopeful strategy for the treatment of distant metastases. The benefits of the combination therapy by an immune stimulator alpha-galactosylceramide (KRN7000) and an angiogenesis inhibitor AGM-1470 (TNP470) were evaluated on the hamster highly aggressive liver metastasis model using the syngeneic pancreatic cancer cell line HPD-NR. KRN7000 immediately activated hepatic mono-nuclear cells to produce IFN-gamma in vitro. Intraportal injection of KRN7000 exhibited a dense accumulation of CD4-CD8- natural killer T cells, around the liver metastases in vivo. KRN7000 treatment significantly inhibited the growth of liver metastases, and importantly, significant survival prolongation was confirmed when TNP470 treatment was added to it. Furthermore, cytotoxic T lymphocytes were induced at the sites of a few residual metastases in the liver of a long-term survivor. Thus, the combination of KRN7000 and TNP470 showed a high effectiveness for the treatment of liver metastases of pancreatic cancer.

Adjuvants, Immunologic↗

PubMedDate not supplied

Impact of vasculogenesis on solid tumor growth in a rat model.

Peripheral stem cells released from bone marrow (BM) are known to be incorporated into foci of neovascularization and to contribute to solid tumor development. In the present rat Walker256 tumor model, BM suppression induced by total body irradiation resulted in poor growth of the tumor with apparently poor vascularization, and BM transplantation restored tumor growth. Endothelial progenitor cells are considered to be crucial for vasculogenesis, but they are not yet well defined, and methodology for their purification has not been established. As a model to examine the significance of endothelial progenitor cells in tumor-specific vasculogenesis, we utilized an immortalized rat BM-derived endothelial cell line named TR-BME-2. Fluorescence-labeled TR-BME-2 cells injected systemically into rats were accumulated at the tumor site 4 days later. Another rat BM-derived cell line named C2-11, which does not have an endothelial profile, did not show tumor-specific accumulation. The tumor volume in rats treated with TR-BME-2 was significantly larger than that in rats treated with C2-11. Thus, our results suggest the importance of neovascularization by bone marrow-derived endothelial cells for the promotion of tumor growth.

Animals↗

PubMedDate not supplied

Protracted administration of weekly docetaxel in metastatic breast cancer.

The purpose of this study was to evaluate the efficacy and toxicity of weekly docetaxel in metastatic breast cancer. Fifty-seven patients were enrolled in this study of weekly docetaxel given at 25 mg/m(2)/week as a 1-h infusion in out-patient setting. Each cycle consisted of 3 weeks of therapy followed by 1-week treatment break, and the patients received a median of 24 infusions with a median cumulative dose of 600 mg/m(2). Overall response rate was 30% [95% confidence interval (CI), 18-42%], and 31% (18-42%) of patients had stable disease for at least 6 months. With a median follow-up of 16 months, the median time to treatment failure was 11 months (6-14 M), and 3-year survival rate was 60%. There was no grade 4 toxicity, and myelosuppression, fatigue, nausea, vomiting was mild, thus the regimen was generally well tolerated. On the other hand, 44% of patients had grade 1-2 nail change, 21% had grade 3 pleural effusion, 17% had grade 1-2 tearing, and these became more common with prolonged administration of docetaxel. Thus, a weekly schedule of docetaxel at low dose maintains activity and is less myelosuppressive, however, one should be careful about cumulative toxicities.

Adult↗

PubMedDate not supplied

Study of cancer gene therapy using IL-12-secreting endothelial progenitor cells in a rat solid tumor model.

To test the hypothesis that genetically modified bone marrow-derived endothelial progenitor cells (EPCs) can be effective carriers of therapeutic agents to tumor sites, we utilized our conditionally immortalized endothelial progenitor cell line, TR-BME-2. In the syngenic rat, systemically injected TR-BME-2 cells were immediately distributed to the organs (lung, bone marrow, peripheral blood, liver, spleen). Trapped cells were cleared within 4 days, but selective accumulation in the Walker256 tumor was maintained for over 4 days. The tumor growth was enhanced by administration of TR-BME-2 cells. It is suggested that accumulated TR-BME-2 differentiated to tumor vasculature, increased the tumor blood supply, and thereby increased the tumor volume. We conducted IL-12 gene transfection of TR-BME-2 cells with a virus vector in vitro, and used the resultant IL-12-secreting TR-BME-2 to deliver IL-12, which strongly activates cytotoxic lymphocytes and natural killer cells, to the tumor site in vivo. However, the tumor-progressive character of TR-BME-2 offset the anti-tumor effect of IL-12. Nevertheless, our results suggest that gene-transfected EPCs could be useful as a tumor-specific drug delivery system, especially if the tumor vasculature-promoting effect of EPCs can be blocked.

Animals↗