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Biomedical subjects

K Orita

Publications and source records attributed to K Orita.

At least 451 records · Page 25Linked to original sources

Coeliac axis-oriented approach in surgery for advanced gastric cancer.

To achieve the systemic curative lymph node dissection in gastrectomy for advanced gastric cancer, coeliac axis-oriented approach was proposed. Mobilization of the spleen as well as the tail and body of the pancreas from the left retroperitoneum and Kocher's maneuver lifting up the hepatoduodenal ligament and head of pancreas from the right retroperitoneum permits the observation of the coeliac axis under direct vision and enables the para-aortic node dissection with ease. This approach was applied to 131 cases with advanced gastric cancer with neither mortality nor notable complication.

Aorta, Abdominal↗

Tumour necrosis factor-alpha upregulates transferrin receptors in K 562 cells.

The effects of tumour necrosis factor-alpha on transferrin receptor expression in a human chronic myelocytic leukaemia cell line, K 562 cells, were studied. Cytofluorometry studies showed that the numbers of transferrin receptors in exponentially growing K 562 cells were increased when the cells were incubated with tumour necrosis factor-alpha for 24 h. The induction of transferrin receptors by tumour necrosis factor-alpha may be mediated by a mechanism that is independent of growth since cell growth in treated cultures did not differ from that in the controls. The DNA contents of K 562 cells treated with tumour necrosis factor-alpha showed that after 24 h there were less cells in the G1 and S phases and more cells in the G2/M phase than in the control group. The phase of upregulation of transferrin receptors induced by tumour necrosis factor-alpha may be dependent on the cell cycle. This new evidence that tumour necrosis factor-alpha upregulates transferrin receptors suggests a cancer-anaemia cascade in which the cancer burden state activates macrophage release of tumour necrosis factor-alpha as a result of transferrin receptor expression.

Cell Cycle↗

Effects of cyclosporine A on experimental hepatic metastases of mouse colon-26 tumour.

Cyclosporine A (CSA), an immunosuppressive agent with apparently selective effects on T lymphocytes and little myelotoxicity, was tested for its effects on hepatic metastases by inoculation of mouse colon-26 tumour cells into the portal vein in male CDF1 mice. CSA, given subcutaneously in daily doses of 10-50 mg/kg/day, for 22 days, significantly increased the incidence of hepatic nodules. This increase was positively correlated with the CSA dose. When 5-fluorouracil was injected at a dose of 15 mg/kg/day every other day after the inoculation of tumour cells a highly significant reduction in the incidence of metastases was seen (compared with the controls). This strong inhibitory effect of 5-fluorouracil on metastasis was almost completely suppressed when mice were treated with CSA concomitantly. The results suggest that CSA affects the host immune system, accelerating the production of hepatic metastases.

Adenocarcinoma↗

Time-course of changes in the plasma-membrane lipid bilayer and cellular ultrastructure induced by tumour necrosis factor-alpha in K 562 and Daudi cells.

The time-course of changes in the plasma-membrane lipid bilayer induced by tumour necrosis factor-alpha (TNF) were investigated in cultured cells using spin-label electron-spin-resonance techniques. Treatment of K 562 cells, a human chronic myelocytic leukaemia cell line, in suspension culture with TNF for up to 6 h caused an initial increase in cell-membrane fluidity, which returned to the control level after 12 h of treatment. After 24 h of treatment, the cell-membrane fluidity had decreased and this decrease was maintained after 48 h of treatment. In Daudi cells, a human malignant lymphoma cell line, TNF, did not induce any changes in cell-membrane fluidity, indicating that the effect of TNF on membrane structure is cell-specific. The early and transient change in membrane fluidity in K 562 cells is probably related to signal generation, while the later, persistent change may reflect the phenotype of TNF-treated cells, in particular, changes in the plasma membrane-cytoplasmic complex. Histochemical electron microscopic studies indicated that the membrane fluidity changes induced by TNF have an ultrastructural correlate.

Cell Membrane↗

Aberration of p53 and DCC in gastric and colorectal cancer.

We investigated the expression of p53 protein by immunohistochemistry and the expression of deleted in colorectal carcinoma (DCC) mRNA by the reverse transcription-polymerase chain reaction (RT-PCR) method in surgically resected tumors of gastric and colorectal cancers and compared these results to the clinicopathological features. Positive immunoreactions of p53 were observed in 21 of 42 gastric cancers (50%) and 25 of 37 colorectal cancers (67.6%). Decreased expression of DCC mRNA was observed in 15 of 38 gastric cancers (39.5%) and 10 of 28 colorectal cancers (35. 7%). There was a significant correlation between the immunoreaction of p53 and the depth of tumor invasion in gastric cancer, as well as between the decreased expression of DCC mRNA and nodal metastasis in colorectal cancer. In early cases without metastasis and invasion beyond muscularis propria, none of six gastric cancers showed a p53 immunoreaction, while seven of 9 colorectal cancers showed positive immunoreactions. On the other hand, two of 4 gastric cancers showed decreased expression of DCC mRNA; whereas, none of the seven colorectal cancers did. Alteration of p53 might occur at a later stage in gastric cancer than in colorectal cancer and be associated with the acquisition of an invasive character. In contrast to gastric cancer, decreased expression of DCC mRNA might be present in a later stage in colorectal cancer than in gastric cancer, and be related to the acquisition of metastatic character to the lymph nodes. In conclusion, alterations of p53 or DCC may play different roles in the progression of gastric cancers as compared to colorectal cancers, and the occurrence of both p53 and DCC genes mutations may cause these cancers to become more malignant.

Colorectal Neoplasms↗

Randomized controlled trial of 5-fluorouracil (5-FU) infusion combined with 1-hexylcarbamoyl-5-fluorouracil (HCFU) oral administration and HCFU alone as postoperative adjuvant chemotherapy for colorectal cancer.

BACKGROUND: Although surgical resectability is an important prognostic factor, recurrences are commonly noted in advanced colorectal cancer patients, even after apparently curative surgery. Because such recurrences cannot be cured, better adjuvant chemotherapies are urgently required. PATIENTS AND METHODS: We studied the effect of postoperative chemotherapy using 1-hexylcarbamoyl-5-fluorouracil (HCFU) oral administration with or without 5-fluorouracil (5-FU) infusion for curatively resected Stage II and III colorectal cancer. This study was prospectively randomized and controlled and 303 (95.6%) of 316 patients were determined to be candidates for statistical assessment. Group A received oral HCFU, 300 mg daily for 52 weeks beginning 2 weeks after surgery. Group B also received 5-FU intravenous injection, 333 mg/m2 body surface area/24 hours continuously for 72 hours beginning on postoperative day 0 and 6. RESULTS: There were no differences in overall 5-year survival or disease-free survival between Groups A and B. Group B had better 5-year disease-free survival (47.6%) than Group A (42.9%) (p = 0.062) and significantly prolonged interval from surgery to recurrence (p = 0.003) for patients with lymph node metastasis. In contrast, group B had significantly shortened 5-year disease-free survival (p = 0.010) and increased recurrence rate in patients without lymph node metastasis. CONCLUSION: Inductive therapy with 5-FU in combination with oral HCFU is beneficial as adjuvant chemotherapy for advanced colorectal cancer with lymph node metastasis.

Administration, Oral↗

Post-operative adjuvant chemotherapy for colorectal cancer with 5-fluorouracil (5-FU) infusion combined with 1-hexylcarbamoyl-5-fluorouracil (HCFU) oral administration after curative resection.

BACKGROUND: Although surgical resectability is an important prognostic factor, recurrences are commonly noted in advanced colorectal cancer patients, even after apparently curative surgery. Since such recurrences cannot be cured, better adjuvant chemotherapies are urgently required. PATIENTS AND METHODS: We studied the effect of post-operative chemotherapy using oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) with 5-fluorouracil (5-FU) infusion for curatively-resected Stage IIIa and IIIb colorectal cancers. This study was prospectively randomized and controlled and 314 (97.8%) out of 321 patients were determined to be candidates for statistical assessment. Group A and Group B received 5-FU intravenous injection at, respectively, 333 mg/m2 and 1000 mg/m2 body surface area/24 hours continuously for 72 hours beginning on post-operative day 0 and day 6, with oral HCFU 300 mg daily for 52 weeks beginning 2 weeks after surgery. RESULTS: There were no differences in overall 5-year survival or disease-free survival between Group A and Group B. A retrospective subset analysis. however, suggested that the protocol of Group B tended to yield better 5-year survival (68.3%) for rectal cancer than that of Group A (58.8%). CONCLUSION: Inductive therapy with high-dose 5-FU in combination with oral HCFU appears to be beneficial as adjuvant chemotherapy for advanced rectal cancer with lymph node metastasis.

Administration, Oral↗

Development of an interleukin-2 slow delivery system.

The authors developed a slow delivery system for interleukin-2 (IL-2) using highly purified bovine collagen to overcome the rapid clearance and side effects of IL-2; 1 X 10(6) microns of recombinant human IL-2 was successfully infused into needle-shaped "IL-2 mini-pellets". Pharmacokinetic study in C57BL/6 mice revealed that a single subcutaneous injection of an IL-2 mini-pellet could prolong IL-2 retention and decrease maximal concentration in the serum. Elimination half-life was 360 min for subcutaneously injected IL-2 mini-pellets, while it was 8 and 15 min, respectively, for intravenous and subcutaneous injections of aqueous IL-2. No side effects were observed throughout the experiment. This slow delivery system using collagen as a carrier proved to be effective and may be applicable to other kinds of drugs.

Animals↗