Biomedical subjects

T Toge

Publications and source records attributed to T Toge.

242 records · Page 14Linked to original sources

PubMedDate not supplied

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↗

PubMedDate not supplied

Factors contributing to adriamycin sensitivity in human xenograft tumors: the relationship between expression of the MDR1, GST-pi and topoisomerase II genes and tumor sensitivity to adriamycin.

To study the factors contributing to tumor sensitivity to adriamycin (ADR) in vivo, the relationship between mRNA expression of the MDR1, GST-pi and topoisomerase II genes and tumor response to ADR was examined in six human xenograft tumors derived from two esophageal, two gastric and two colon cancers. A significant tumor response to ADR was observed in two esophageal xenograft tumors of six tumor lines, and one gastric tumor partially responded to ADR. mRNA expression of the MDR1 and GST-pi genes was elevated in five tumor lines including three ADR responsive tumors, whereas mRNA expression of the topoisomerase II gene was detected in all six tested tumor lines. Topoisomerase II mRNA expression levels in ADR responsive tumors were higher compared with those of ADR unresponsive tumors. No significant relationship between mRNA expression of the MDR1 and GST-pi genes and ADR sensitivity was found. In contrast, topoisomerase II mRNA expression was significantly correlated with tumor sensitivity to ADR (p less than 0.01). Moreover, topoisomerase II mRNA expression was significantly correlated with the growth fraction (S-phase fraction) in the cell cycle kinetics (p less than 0.01). These results indicate that topoisomerase II mRNA expression in association with the high growth fraction may be an important in vivo factor to contribute to ADR sensitivity in human tumors.

Animals↗

PubMedDate not supplied

A role for plasma membrane potential in doxorubicin--induced cytotoxicity.

Using a modifier of membrane function, we have shown that plasma membrane potential plays an important role in doxorubicin (DOX) - induced cytotoxicity through its connection with cell metabolism and through its effect on drug accumulation. Membrane potential of K562 cells, measured using 3, 3'-dihexyl-oxacarbocyanine (DiOC6 (3)), was increased in the presence of non-toxic cepharanthin or N-1379 and decreased in the presence of non-toxic K252a. Correlated with the level of the potential, DOX efficacy was enhanced by cepharanthin or N-1379 and decreased by K252a associated with an increase or decrease of the percentage of cells in S-phase and of intracellular DOX accumulation.

Alkaloids↗

PubMedDate not supplied

Expression of MDR1, GST-pi and topoisomerase II as an indicator of clinical response to adriamycin.

The usefulness of MDR1, GST-pi or topoisomerase II mRNA expression detected by dot blot analysis as an indicator of intrinsic resistance to adriamycin was investigated in 15 fresh human tumor specimens. MDR1 and GST-pi expression, which is known to be a marker for adriamycin resistance, was detected in six (66.7%) and seven (77.8%) of the nine clinically resistant tumors, respectively. However, in four of the six adriamycin responsive tumors, MDR1 and/or GST-pi expression were detected. Thus these two markers were not indicators of clinical response to adriamycin. In contrast, topoisomerase II mRNA expression was significantly correlated with clinical response (p less than 0.01, chi 2 test). The expression of topoisomerase II mRNA was detected at a high level in five (83.3%) of the 6 clinically responsive tumors, and the other nine tumors resistant to adriamycin treatment exhibited undetectable or low levels of topoisomerase II mRNA. We therefore suggest that the level of topoisomerase II mRNA expression is a useful marker of the clinical response to adriamycin.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Antitumor effect of KW2149, a new mitomycin derivative, administered by different modalities.

The effectiveness of a new mitomycin derivative, KW2149, against human tumors was evaluated by the 4 days subrenal capsule assay (SRCA) and the nude mice screening assay (NMSA). Evaluation by the SRCA showed a 50% response rate at a maximum dose of 3.8 mg/kg for 3 consecutive days. When evaluated by NMSA, the response rate was 100, 75 and 25% after the intermittent administration of 7.5, 5.6 and 4.5 mg/kg (q4dx3) respectively. Although the efficacy was reduced when mice were administered a single dose equivalent to the intermittent one, the new analog was along more effective than MMC administered by either modality.

Adenocarcinoma↗

PubMedDate not supplied

Defective natural killer activity in gastric cancer patients: possible involvement of suppressor factor receptor.

The mechanism of defective natural killer (NK) activity in gastric cancer patients was studied with respect to the soluble immune suppressor factor receptor on NK cells. Phycoerythrin (PE)-conjugated anti-CD8 and -CD16 antibodies were used for the determination of NK phenotype, and fluorescein isothiocyanate (FITC)-conjugated wheat germ agglutinin (WGA) was for the lymphocyte surface receptor of soluble immune suppressor factor (SISF). It was found that NK activity of peripheral blood lymphocytes (PBLs) isolated from gactric cancer patients decreased with tumor progression in spite of an increasing tendency of their CD16+ population. The WGA+ population of PBLs inversely increased in parallel with cancer progression and a significant negative correlation was found between NK activity and the WGA+ population. Two-color flow cytometry showed a significant increase of WGA+ cells in the CD8dim and CD16+ population in advanced cancer patients. It is suggested that an increase of surface receptors for SISF on NK cells may, in part, cause the diminished NK activity in gastric cancer patients.

Antibodies, Monoclonal↗

PubMedDate not supplied

Stromelysin-3 mRNA expression and malignancy: comparison with clinicopathological features and type IV collagenase mRNA expression in breast tumors.

mRNA expression of stromelysin-3 (ST3) and 72K type IV collagenase (cIVase) in 4 human breast cancer cell lines and 55 resected breast tumors were examined using Northern blot analysis. In 4 cell lines ST3 was not expressed at all, while cIVase gene expression was detected in 3 of them. The ST3 expression was found more specifically in malignant tumors (39/40, 97.5%) than in benign ones (4/15, 26.7%), although cIVase was expressed in all tumor specimens. The quantitative analysis showed that ST3 expression in malignancies was significantly greater than that in benign tumors (P = 0.0007), while cIVase expression was not (P = 0.1381). ST3 gene expression was also closely related to the presence of lymph node metastasis (P = 0.047), while cIVase was not (P = 0.1091). These results suggest, therefore, that ST3 is expressed more specifically by stromal cells surrounding cancer cells than cIVase. Since ST3 mRNA expression was independent of the EGFR, ER and erbB2 protein expression, ST3 may be a new potent prognostic guide for breast carcinomas, which can detect highly malignant subpopulations.

Breast Neoplasms↗

PubMedDate not supplied

Locoregional immunotherapy of malignant ascites by intraperitoneal administration of OK-432 plus IL-2 in gastric cancer patients.

The clinical efficacy of intraperitoneal administration of OK-432 plus interleukin-2 (IL-2) for treating malignant ascites was evaluated in gastric cancer patients. Ten KE of OK-432 and 200,000 Jurkat units of IL-2 were intraperitoneally administered in tandem in the order given on alternate days at paracentesis. Of the 22 evaluable patients, 18 (81%) developed complete or partial responses, showing a cytologic disappearance of cancer cells and decrease of ascites. More than 50% of the patients obtained positive responses within 2 weeks after the initial administration of the drugs. Improvements of performance status and clinical symptoms such as abdominal fullness, followed by restoration of oral food intake and prolongation of survival time were observed in responders treated with OK-432 plus IL-2. Flow cytometric analysis demonstrated a predominant increase of the CD3+CD4+ cells, especially of the CD4+CD45RA- subset in the peritoneal cavity of the responders. Cytotoxicity assay after negative selection of the CD4+ cells with the antibody and complement revealed that the CD4+ subset possessed cytotoxic activity against autologous tumor cells. The results suggest that intraperitoneal administration of OK-432 plus IL-2 may not be only a practical but also an effective protocol for treating malignant ascites in gastric cancer patients.

Adult↗