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Biomedical subjects

T Ozasa

Publications and source records attributed to T Ozasa.

At least 19 recordsLinked to original sources
PubMed2000

[Continuous hepatic arterial infusion of 5-fluorouracil with leucovorin for unresectable liver metastases from colorectal cancer].

Twenty-three patients with liver metastases from colorectal cancer were treated by continuous hepatic arterial infusion chemotherapy with 5-FU and Leucovorin. The regimen was that 500 mg/body of 5-FU with 30 mg/body of Leucovorin was administered continuously for 5 days, followed by no medication for 16 days. The effect of this therapy was evaluated and the relationship between this therapy and the overexpression of vascular endothelial growth factor (VEGF) or microvessel density (MVD) was also studied. Complete response was obtained in 4 patients and partial response in 3 patients; the response rate was 32%. The response rate was 60% in patients who underwent more than 7 courses. The response rate was 44% in patients with positive VEGF and 33% in patients with negative VEGF. The response rate was 50% in patients with an MVD of more than 30 and 33% in patients with an MVD of less than 30. The 3-year survival rate for patients who underwent more than 7 courses was 37.5%. This therapy had to be abandoned in 6 patients due to occlusion of the catheter. Skillful maintenance of the catheter is necessary for a high response rate and satisfactory prognosis using this therapy.

Aged↗
PubMed1999

Clinicopathological variables and p53 overexpression as a combined prognosticator for hematogenic recurrence in colorectal cancer.

BACKGROUND AND OBJECTIVE: Precise evaluation of the prognostic factors for hematogenic recurrence after resection for colorectal cancer is important not only for the prediction of patient outcome but also for the determination of adjuvant therapy. The purpose of the current study was to elucidate the clinical significance of using clinicopathological variables in combination with p53 expression as a prognosticator for hematogenic recurrence. METHODS: One hundred forty-two patients with colorectal cancer were examined. The expression of p53 was determined by immunohistochemical staining. RESULTS: Eighteen (60%) of the 30 patients who were positive for both p53 overexpression and lymph node metastasis, 13 (41%) of the 32 patients who were positive for p53 and venous invasion, and 13 (39%) of the 33 patients who were positive for p53 and carcinoembryonic antigen (CEA) developed hematogenic recurrence. CONCLUSIONS: The combination of p53 overexpression and lymph node metastasis was an excellent prognostic indicator for hematogenic recurrence in colorectal cancer.

Adult↗
PubMed1998

[Significance of p53 and VEGF expression in liver metastasis from colorectal cancer].

We examined the significance of expression of p53 and vascular endothelial growth factor (VEGF) on the liver metastasis in 155 patients with colorectal cancer. The expression of p53, VEGF, and microvessel density (MVD) were immunohistochemically studied. There were significant differences between patients positive for p53 and patients negative for p53, between patients positive for VEGF and patients negative for VEGF, with respect to the occurrence of liver metastases. The frequency of patients positive for both p53 and VEGF in the liver metastases group was significantly higher than that in the control group. The frequency of patients positive for both p53 and v, both VEGF and v in the liver metastases group, was significantly higher than in the control group. MVD in patients positive for VEGF was significantly higher than that negative for VEGF. Thus, p53 and VEGF expression affects the formation of liver metastases from colorectal cancer by the activation of neovascularization followed by feasibility of the extravasation of tumor cells in the tumor tissue.

Colorectal Neoplasms↗
PubMed1998

[Clinicopathological significance of p53 overexpression in elderly patients with colorectal cancer].

The purpose of this study was to elucidate the clinicopathological significance of p53 overexpression in elderly patients with colorectal cancer. p53 positivity for elderly patients and control was 41% and 57%, respectively. There was a significant difference between these two groups. Regarding the rate of hematogenic metastases, there was no significant difference between patients with positive for p53 and negative for p53 in the elderly group (44% vs 39%), on the other hand, there was a significant difference between patients with positive for p53 and negative for p53 in the control group (70% vs 48%). Regarding prognosis, there was no significant difference between patients with positive for p53 and negative for p53 in the elderly group (73.3% vs 72%), on the other hand, there was a significant difference between patients with positive for p53 and negative for p53 in the control group (51.2% vs 68.7%). These results suggest that the significance of p53 overexpression was negligible in elderly patients with colorectal cancer.

Adult↗
PubMed1997

Cytokine gene expression in pancreatic islet grafts in the rat.

We examined the production of cytokine message in allogeneic and syngeneic rat pancreatic islet grafts using specific primers and polymerase chain reaction. Freshly isolated islet preparations contained transcripts for interleukin (IL)-1alpha, IL-6, IL-10, and interferon-gamma (IFN-gamma) but not for IL-2. IL-1alpha in allogeneic grafts showed increased and consistently high expression from 1 to 7 days after transplantation, but the level in syngeneic grafts fell quickly to pretransplant levels. IL-2 and IFN-gamma transcripts were found in allogeneic grafts at 1, 3, 5, and 7 days after transplantation with a peak at day 5, but these cytokines were almost absent from syngeneic grafts. The peak of IL-6 expression was 1 day after transplantation in both syngeneic and allogeneic grafts, and then the level fell quickly. IL-10 was produced at approximately the same high level at all time points in both syngeneic and allogeneic grafts. The results show that freshly isolated islet preparations contain IL-1alpha, IL-6, IL-10, and IFN-gamma transcripts at the time of transplantation. The initial production of cytokines in islet grafts, especially IL-1, may explain phenomena such as graft nonfunction, rapid rejection, and lack of response to immunosuppression.

Animals↗
PubMed1997

Multivariate analysis of the prognostic factors of patients with unresectable synchronous liver metastases from colorectal cancer.

PURPOSE: It frequently is observed that widely varying prognoses are given for patients with the same extent of liver metastases from colorectal cancer, even though the same treatment is performed on these patients. One of the reasons for this variance is that prognostic factors for these patients have not been defined. This study was designed to elucidate which clinicopathologic factors were the most important in the prognosis of 73 patients with unresectable synchronous liver metastasis from colorectal cancer. METHODS: Univariate and multivariate analysis of 11 clinicopathologic factors were performed using the Cox proportional hazard model. Survival curves were generated using the Kaplan-Meier method. RESULTS: Extent of liver metastases was the most significant variable in this survival analysis, although the extent of lymph node metastases of the primary lesion also was significant. However, the method of treatment was not a significant determinant in the survival for patients with unresectable liver metastases. Median survival of patients with H1, H2, and H3 was 13, 12, and 6 months, respectively, and there was a significant difference between survival curves for patients with H1 and patients with H3. Median survival of patients with n0, n1, and n2 was 13, 7, and 7 months respectively, and there was a significant difference between survival curves for patients with n0 and patients with n2. Median survival of 6 patients with H1 and n0 and of 17 patients with H3 and n2 was 28 and 4 months, respectively. There was a significant difference in survival curves between these two groups. CONCLUSION: Longevity of patients with unresectable synchronous liver metastases from colorectal cancer is affected adversely by the presence of nodal metastases and extent of liver metastases. This should be considered in the planning treatment.

Adult↗
PubMed1996

In vitro studies on a new method for islet microencapsulation using a thermoreversible gelation polymer, N-isopropylacrylamide-based copolymer.

Various materials for the semipermeable membrane for microencapsulation of islets, such as alginate complex and agarose, have been used. In this study, a thermoreversible gelation polymer, N-isopropylacrylamide based copolymer was used to make microencapsulated islets and was examined in vitro. The polymer has little or no cytotoxicity for human dermal fibroblasts. The characteristics of viscoelasticity below the soluble gel transition temperature (SGTT) and of thermoreversibility, the water soluble polymer below the SGTT (22 degrees C) becoming water insoluble upon heating, contributed to simplifying the encapsulation technique. We obtained viable islets at the center of the membrane with a thickness of approximately 20-50 microns, accounting for a 40% yield of encapsulated islets. Static glucose challenge test with microencapsulated islets revealed the insulin response to the concentration of glucose. The insulin concentrations of the culture medium in the microencapsulated islet group were the same as those in a similar free islet group up to 42 days. These results indicate that the morphological and functional stability of the new method for microencapsulation may be sufficient for it to be used for transplantation in diabetic animals.

Acrylamides↗
PubMed1996

YM-24074, a new peptide antibiotic. II. Structural elucidation.

YM-24074 (formerly called YL-01869P) is a new antibiotic and type I collagenase inhibitor. The structure of this compound was elucidated by spectroscopic analysis and confirmed by acid degradation to be N-(1"-acetyl-3"-methylbutyl)-2- [2'-[(N-hydroxycarbamoyl)methyl]heptanoyl]-hexahydropyrid azine-3-carboxamide. The stereochemistry of two of three chiral centers was determined by degradation products to be 3S, 2'R.

Anti-Bacterial Agents↗
PubMed1996

[The effect of intraportal chemotherapy in terms of administered dose of 5-FU].

Forty-six patients with colorectal cancer were studied for the effects of intraportal chemotherapy in terms of the administered dose of 5-FU. No liver metastases occurred in patients with a total dose of more than 4 g of 5-FU. The five-year survival rate for patients with a total dose of more than 4 g of 5-FU was 98%, which was better than that for control (72%). In patients administered 500 approximately 600 mg/body/day of 5-FU, the concentration of 5-FU in the peripheral blood was 0.022 approximately 0.027 microgram/ml. Liver dysfunction occurred in 22%, 33%, and 80% of patients administered less than 4 g, 4 approximately 4.9 g, or more than 5 g of 5-FU, respectively, but almost all of them were grade 1. These results suggest that intraportal chemotherapy administered with a total of more than 4 g of 5-FU was effective for prevention of liver metastases after resection of colorectal cancer.

Colorectal Neoplasms↗
PubMed1995

[Pharmacokinetic study in biochemical modulation therapy of UFT with leucovorin tablet].

Preoperative oral treatment with UFT and leucovorin tablet was performed. Pharmacokinetics, degree of degeneration in the tumor tissue and side effects were studied in 34 patients with colorectal cancer preoperatively given 400 mg/day of UFT with 20 mg/day of leucovorin tablet or 400 mg/day of UFT alone. Results were as follows; 1) there was no significant difference between UFTL group and UFT group regarding concentration of FdUMP in the tumor tissue. In UFTL group, concentration of FdUMP was higher in the tumor tissue of moderately differentiated adenocarcinoma than that of well differentiated adenocarcinoma. No significant differences regarding concentration of FdUMP were obtained between diploid and aneuploid groups. 2) TS inhibition rate in the tumor tissue was 66.8% in UFTL group and 53.2% in UFT group, and there was a significant difference between these two groups. TS inhibition rate in the tumor tissue was higher than that in the normal tissue either in UFTL group or UFT group. However, there were no significant differences of TS inhibition rates regarding differentiation of tumor tissue or DNA ploidy pattern. 3) Degree of degeneration of more than Grade 2 was not obtained in any patients of either UFTL or UFT group. 4) There was no change in blood laboratory data between before and after medication. Only one patient complained Grade 1 pruritus in UFTL group. These results suggest that oral biochemical modulation therapy of UFT with leucovorin tablet is effective because of pharmacokinetically high anti-tumor effect and minimal side effects.

Adenocarcinoma↗
PubMed1994

Immediate destruction of xenogeneic islets in a primate model.

Transplantation of pancreatic islets from other species to man has the potential to cure diabetes, but whether such islet grafts will be subject to damage due to natural antibody-mediated hyperacute rejection is unknown. We have examined the fate of islet xenografts in a recipient with direct relevance to man, the cynomolgus monkey. Rabbit islets were prepared by an intraductal collagenase technique and incubated in neat rabbit, human, or cynomolgus serum, with and without heat inactivation, for up to 6 days. Islets were analyzed by flow cytometry for IGG and IGM binding, and scored for viability by supravital staining. For in vivo studies, isolated islets were prepared from 4 New Zealand White rabbits (15-34 x 10(3) islets 70-85% purity) and transplanted beneath the kidney capsule of normal cynomolgus monkeys after aggregation in either a rabbit or monkey blood clot. The tissue was retrieved at various times up to 4 days after transplantation and processed for light and electron microscopy. The results showed that rabbit islets bind heterophile antibody of both IGG and IGM subtypes. There was slow loss of islet viability in vitro over 3 days of culture in neat human or cynomolgus serum. Destruction of islets in vivo was more rapid with visible damage within 6 hr associated with neutrophil infiltration. Subsequently, there was heavy mononuclear cell infiltration leading to total destruction within 4 days. The results suggest that immediate mechanisms of graft rejection, possibly compliment and neutrophil mediated, represent a major barrier to islet xenotransplantation in humans.

Animals↗
PubMed1994

[Pharmacokinetic studies on continuous intraportal 5-fluorouracil infusion].

Pharmacokinetics of 5-FU administered by continuous intraportal infusion were studied by infusing 5 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg of 5-FU, respectively, into the ileocecal vein for an hour. Blood samples were collected from portal vein, femoral vein and liver, and small intestine specimens were obtained at proper intervals. The rabbits were sacrificed at 120 minutes from the start of 5-FU infusion. The results were as follows: Extremely high concentrations of 5-FU in the portal vein, femoral vein and liver tissue were observed in the 5-FU group infused with 40 mg/kg. This phenomenon was suggested to rely on the effect by which the 5-FU catabolic enzyme, dihydrouracil dehydrogenase, was saturated with a large inflow of 5-FU. FdUMP concentration of the liver was lower than that of the small intestine in all groups. These results suggest that a large dose of 5-FU infusion is effective to increase the FdUMP concentration in the liver with continuous intraportal 5-FU infusion.

Animals↗
PubMed1993

[Arterial infusion chemotherapy of 5-FU and leucovorin for patients with liver metastases from colorectal cancer].

Fifteen patients with liver metastases from colorectal cancer were treated by arterial infusion of 5-FU and leucovorin. Two regimens were performed. One was weekly bolus infusion of leucovorin following bolus infusion of 5-FU (bolus group), the other was 5 days continuous infusion of 5-FU and leucovorin in 3 weeks (continuous group). One PR was obtained both in the bolus group and in the continuous groups. The objective response rate was 11% in the bolus group and 20% in the continuous group. The one- and 2-year survival rates for these patients were 40% and 0% in the bolus group, and 80% and 60% in the continuous group, respectively. These results suggest that continuous arterial infusion of 5-FU and leucovorin was more effective than individual bolus arterial infusion of leucovorin and 5-FU for patients with liver metastases from colorectal cancer.

Adult↗
PubMed1992

[Pharmacokinetic studies of continuous and bolus intraportal 5-fluorouracil infusion].

We studied the pharmacokinetics of continuous and bolus intraportal 5-FU infusion. In continuous intraportal infusion group, 20 mg/kg of 5-FU was infused into ileocecal vein for an hour and the same dose was infused bolusly in bolus intraportal infusion group. Blood samples were collected from portal vein continuously and liver specimens were obtained continuously. The rabbits were sacrificed at 180 minutes from the start of infusion of 5-FU and small intestine was obtained. The results were as follows: A significantly higher concentration of 5-FU in the portal vein was observed in the continuous intraportal infusion group compared with the one-shot infusion group. But the elimination rate of 5-FU was more rapid after cessation of infusion in the continuous infusion group. The rate of FdUMP elimination in the liver tended to be lower in bolus intraportal infusion. The FdUMP concentration in the small intestine was higher in the continuous intraportal infusion group than in the bolus infusion group. In the continuous intraportal infusion group, the FdUMP concentration in the liver was lower than in the small intestine. This depended on the effect of the 5-FU catabolic enzyme, dihydrouracil dehydrogenase, which is contained in the liver in large quantities. The results suggest that in order to increase the FdUMP concentration in the liver with continuous intraportal 5-FU infusion, suppression of the effect of this enzyme is necessary.

Animals↗