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Biomedical subjects

T Kusumoto

Publications and source records attributed to T Kusumoto.

At least 55 records · Page 3Linked to original sources
PubMed1992

A simple procedure for intrahepatic biliary drainage in patients with obstructive jaundice owing to a recurrence of cancer following reconstructive gastric surgery.

We designed a simple and reliable method of intrahepatic biliary drainage for patients with obstructive jaundice owing to a recurrent gastric cancer. This approach can be used for selected patients treated by partial gastrectomy and reconstructive surgery, using the Billroth II procedure and antecolic anastomosis. Anastomosis between the intrahepatic bile duct and the afferent jejunal loop is performed at the anterior edge of the liver, thus facilitating the prevention of recurrence of jaundice caused by tumor infiltration. Application of this technique led to a long-term palliation, control of the jaundice and a fairly normal life.

Adult↗
PubMed1991

Prognostic factors in Japanese patients with colorectal cancer: the significance of large bowel obstruction--univariate and multivariate analyses.

In order to define prognostic factors in colorectal carcinoma, univariate and multivariate analyses were carried out on data from 113 Japanese patients treated in a typical general hospital in Japan. In the univariate analysis, a poor prognosis was seen in those with poorly differentiated adenocarcinoma, in tumors that perforated the visceral peritoneum or that invaded directly other organs or structures (T4), in metastasis to the nodes along the main vascular pedicle (N3), in lymphatic permeation, in blood vessel invasion, in peritoneal dissemination, in Dukes C stage, and in those with lesions presenting with large bowel obstruction. Of these, only lymph node metastasis and peritoneal dissemination had an independent prognostic significance when a multivariate Cox analysis was performed. The significant risk factors related to an obstructing tumor were determined by multivariate logistic regression analysis. The significant variables were patient's age, nodal involvement and peritoneal dissemination. Since lymph node metastasis and peritoneal dissemination proved significant in both multivariate analyses, we propose that the presence of large bowel obstruction is not an independent prognostic factor in patients with colorectal carcinoma. In poor-risk patients who have an obstructing tumor, a staged operation should be attempted for definitive curative surgery.

Adenocarcinoma↗
PubMed1991

1-Hexylcarbamoyl-5-fluorouracil alters the expression of heat shock protein in HeLa cells.

We determined the effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU), a masked compound of 5-fluorouracil, on the expression of heat shock protein (HSP) in heat-treated HeLa cells. We used a monoclonal anti-72-kDa heat shock protein antibody. At 37 degrees C, HSP was predominant in the cytoplasm of cells and heating to 43 degrees C for 30 min increased the synthesis of HSP in the nucleus. When HeLa cells were treated with heat and HCFU, at a concentration which showed evidence of synergy, nuclear staining of the cells decreased. Thus, the altered expression of HSP by HCFU is related to a synergism between heat and HCFU.

Cells, Cultured↗
PubMed1991

Dipyridamole combination chemotherapy can be used safely in treating gastric cancer patients.

The feasibility of a combined chemotherapy using dipyridamole (DP) with adriamycin (ADM) and 5-fluorouracil (5-FU) was investigated. First, the chemosensitivity of gastric cancer tissues was determined by the succinate dehydrogenase inhibition test, which showed sensitivity to ADM and 5-FU is increased by DP. Next, a clinical trial of combined therapy of DP, ADM and 5-FU, as a post-operative adjuvant chemotherapy for gastric cancer patients, was performed. DP (50 mg) was given as a 1-h i.v. infusion, and ADM (20 mg) was given as a single i.v. injection. This treatment was started on post-operative day 10, and was repeated every 2 weeks. Simultaneously with these treatments, DP (300 mg) and 5-FU (150 mg) were administered post-operatively daily. A total of 63 courses of therapy in nine patients were performed. The adverse effects related to the DP infusion were flushing, headache, nausea and upper abdominal discomfort, all of a low grade. DP did not appear to alter the toxicity of ADM and 5-FU, and no severe adverse effect was noted for this combination therapy. The pharmacokinetics of DP were also investigated in five patients. The mean plasma concentration of DP increased 4.41 micrograms/ml and remained above 0.25 microgram/ml for over 6 h. This combination chemotherapy appears to be safe and may be useful clinically in treating cancer.

Adult↗
PubMed1991

The microtiter SDI test is more advantageous than the SDI test for assessing the chemosensitivity of human tumor cells.

The in vitro succinate dehydrogenase inhibition (SDI) test was adapted to be used with microtiter plates and this microtiter SDI (mSDI) test was evaluated for clinical use of chemosensitivity testing, as compared to findings with the SDI test. The optimal conditions of the mSDI test were determined: (1) 2-5 x 10(4) cells/well; (2) enzymatic disaggregation of solid tumors with the use of a mixture of 0.2% pronase, 0.25% collagenase, 0.1% DNase for 20 min at 37 degrees C; (3) addition of 10 mM sodium succinate in the colorimetric reaction; and (4) use of dimethyl sulfoxide (DMSO) as a solvent for extraction of formazan product. Good correlations were observed between the mSDI and the SDI tests when S-180 cells (r = 0.890-0.996) or 16 human fresh tumor cells (r = 0.731-0.999) were exposed to six anti-cancer drugs (carboquone, adriamycin, mitomycin C, aclacinomycin A, cisplatin, 5-fluorouracil). Thus, the mSDI test facilitates testing of a large number of drugs with minimal amounts of specimens, and is expected to replace the SDI test for chemosensitivity testing of clinical tumor cells.

Animals↗
PubMed1991

Sarcoma-180 cells and human colorectal tumor cells under in vitro hypoxic conditions are more sensitive to mitomycin C and carboquone.

The effects of oxygen concentration on the chemosensitivity of mouse sarcoma-180 (S-180) cells and human colorectal cancer tissues to mitomycin C (MMC) or carboquone (CQ) were determined in vitro, since evidence had been obtained that these drugs are more effective in HeLa cells. The results were as follows: (a) S-180 cells exposed to various concentrations of MMC or CQ for 2 h under conditions of normal aeration (about 20%) or hypoxia (5.0% and 0%) were then maintained under normal conditions of aeration for 3 days. Change of viability was assessed by succinate dehydrogenase (SD) activity. With exposure of the cells to MMC or CQ, under anoxic conditions (O2:0%), SD activity decreased to a greater extent than seen in the control cells. The value for CQ was from 61.5% to about 36.2%. (b) The decrease in the SD activity of 20 colorectal cancer tissues kept under conditions of anoxia was compared with findings under normally aerated conditions, following exposure to 30 microM of MMC or 1.6 microM of CQ. On exposure to MMC or CQ under anoxic conditions, SD activity decreased significantly, compared with normally aerated conditions (P less than 0.001 for MMC; P less than 0.05 for CQ). As colorectal cancer is less sensitive than other tissues to various chemotherapeutic agents, we recommend that MMC and CQ be prescribed to treat patients with these malignant lesions.

Alkylating Agents↗
PubMed1990

Primary and metastatic liver lesions of clinical colorectal cancer differ in chemosensitivity.

The succinate dehydrogenase inhibition (SDI) test was used to examine eight pairs of samples obtained simultaneously from primary colorectal cancers and metastatic liver lesions. The chemosensitivity of the metastatic lesions to six antitumour drugs, carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP), and 5-fluorouracil (5-FU), differed from that of the primary lesions - the metastatic lesions were less sensitive to all these drugs. There were no correlations of chemosensitivities between the primary and the metastatic lesions (r = -0.4331-0.4857). Thus, in patients with liver metastasis from a primary colorectal cancer, treatment with these drugs may not be so effective. When selecting antitumour drugs for metastatic liver lesions of colorectal cancer, the chemosensitivity of the primary tumour should first be assessed.

Antineoplastic Agents↗
PubMed1990

Estrogen-receptor-negative breast cancer tissue is chemosensitive in vitro compared with estrogen-receptor-positive tissue.

The chemosensitivities of 18 estrogen-receptor-positive (ER+) tissues were compared with that of 38 estrogen-receptor-negative (ER-) tissues, using the in vitro succinate dehydrogenase inhibition test. These human breast tissue were exposed to six antitumor drugs: carboquone, adriamycin, mitomycin C, aclacinomycin A, cisplatin and 5-fluorouracil. Decrease in succinate dehydrogenase activity was noted in ER- compared to ER+ tissues, exposed to six antitumor drugs, in particular to adriamycin (p less than 0.001) and aclacinomycin A (p less than 0.05). The sensitive rates were higher in ER- than in ER+ tissues, against all six antitumor drugs. The resistance rates to all drugs tested were 25% in ER- and 45% in ER+ tissues. A higher chemosensitivity is associated with the absence of ER. It appeared that the ER status in case of breast cancer is an important predictor of the response to chemotherapy.

Aging↗
PubMed1990

Detection of DNA strand breaks in HeLa cells in vitro and in mouse sarcoma 180 cells in vivo induced by an alkylating agent, carboquone, using in situ nick translation.

We determined the correlation between DNA strand breaks and the toxicity of carboquone (CQ) in HeLa cells in vitro and in mouse sarcoma 180 (S-180) cells in vivo, using in situ nick translation. The break sites in the DNA were translated artificially in the presence of Escherichia coli DNA polymerase I and [3-H]-labelled dTTP, and sites in the DNA were visualized by autoradiographic observation of grains in the nuclei. These breaks appeared as early as 5 min in the CQ-treated HeLa cells and increased in a dose- and time-dependent manner compared to findings in the control cells, i.e., 10.2-fold at 3 x 10(-6) M in 60 min. Strand breaks in the S-180 cells appeared in a dose- and time-dependent manner, i.e., 6.1-fold after the mice had been exposed to CQ (3.6 mg/kg) for 2 h. This level correlated with the increase in host life span. Our findings show that the survival response of cells decreases, while the level of DNA strand breaks increases following exposure to CQ. The nick translation method is a rapid in situ assay for determining drug-induced DNA damage of tumor cells, under in vitro and in vivo conditions and in a semiquantitative manner.

Animals↗
PubMed1989

5-Fluorouracil and UFT-sensitive gastric carcinoma has a high level of thymidylate synthase.

The authors examined the relationship between the level of thymidylate synthase (TS) and the sensitivity to 5-fluorouracil (5-FU) and UFT, a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil in a molar ratio of 1:4. For the studies we used the subrenal capsule (SRC) assay and 15 human gastric cancer tissues. The TS levels were assayed by the ligand-binding technique, using [6-3H]FdUMP. The relative variation of tumor size (delta TuS/TuS0) was calculated to be as follows: delta TuS/TuS0 = [(TuS6 - TuS0)/TuS0] x 100 (%), where TuS6 was the tumor size on day 6 and TuS0 on day 0. The chemosensitivity was considered to be positive when delta TuS/TuS0 in the treated group decreased to below -10%. Decrease in tumor size was marked in case of exposure to UFT (-19.8 +/- 13.0%) (mean +/- standard deviation), compared with that to 5-FU (-9.0 +/- 7.2%), with a statistically significant difference (P less than 0.001). The TS level varied from 1.7 to 30.8 pmol/g gastric cancer tissue and the mean was 7.1 +/- 7.2 pmol/g tissue. A correlation was noted between the TS level and decrease in size of the tumor exposed to 5-FU (r = -0.671) or UFT (r = -0.758): gastric cancer tissue with higher level of TS is more sensitive to 5-FU and UFT than is that with a lower TS level. These findings show that the sensitivity to 5-FU and UFT of gastric cancer tissue is related to the TS level and that UFT shows promise for the treatment of patients with gastric cancer.

Animals↗
PubMed1989

Pyrimidine nucleotide synthesis is more extensive in poorly differentiated than in well-differentiated human gastric carcinoma.

In tissues obtained from patients undergoing gastrectomy, the activities of 12 enzymes involved in pyrimidine nucleotide synthesis: cytidine triphosphate (CTP) synthetase, deoxycytidine monophosphate (dCMP) deaminase, thymidine monophosphate (dTMP) kinase, uridine (Urd), deoxycytidine (dCyd) and thymidine (dThd) kinases, Urd, deoxyuridine (dUrd) and dThd phosphorylases, cytidine (Cyd) and dCyd deaminases, and DNA polymerase were examined in the eight-well-differentiated and 12 poorly differentiated gastric cancer tissues and the ten normal tissues. These cases were clinically advanced and serosal invasions were evident. Activities of these enzymes were higher in the poorly differentiated tissues than the well differentiated type and in the normal tissues. Significant differences were noted between the poorly differentiated and well-differentiated types, in dTMP kinase (P less than 0.02), dThd kinase (P less than 0.05), dThd phosphorylase (P less than 0.01), and DNA polymerase (P less than 0.05). The authors' findings show that the level of pyrimidine nucleotide synthesis, in both de novo and salvage pathways, is higher in the poorly differentiated gastric cancer tissues than in the well-differentiated type and suggest that antitumor drugs have an increased susceptibility in cases of poorly differentiated gastric carcinoma.

Adenocarcinoma↗
PubMed1989

Tumor tissue is more sensitive to mitomycin C, carboquone, and aclacinomycin A than is adjacent normal tissue in vitro.

In tissues obtained from patients undergoing gastrectomy or colectomy, sensitivity to mitomycin C (MMC), carboquone (CQ), and aclacinomycin A (ACR) was examined in 20 tumors (15 gastric, 5 colorectal) and in the adjacent normal mucosal tissues, using the in vitro succinate dehydrogenase inhibition test. The succinate dehydrogenase (SD) activity decreased to a greater extent in the tumor tissues than in adjacent normal tissues, at rates of 80% for MMC, 80% for CQ, and 90% for ACR. There were no correlations between SD activities of tumor and adjacent normal tissue, r = 0.157 for MMC, r = 0.435 for CQ, and r = 0.375 for ACR. Normal tissues were sensitive to MMC in 25% of cases sensitive to MMC in the tumor tissues, 46% for CQ, and 38% for ACR. These results show that the antitumor effects of MMC, CQ, and ACR are relatively specific for tumor tissues and that the assay of chemosensitivity of normal tissues is meaningful for predicting the toxic effects of antitumor drugs on these tissues.

Aclarubicin↗
PubMed1989

Sarcoma-180 cells are more sensitive to heat than are mouse normal tissues: esophagus, stomach, small intestine, large intestine, liver, spleen, and kidney.

Sensitivity of various mouse tissues to heat was determined using mouse sarcoma-180 (S-180) cells and normal tissues: esophagus, stomach, small intestine, large intestine, liver, spleen, and kidney. The in vitro succinate dehydrogenase inhibition (SDI) test was used. The succinate dehydrogenase (SD) activity of tissue fragments was assayed, following exposure to a temperature of 43 degrees C (heat treatment) or 37 degrees C (control) for 1, 2, 5, or 10 hr. The sensitivity to heat treatment was estimated by the percentage of SD activity of the heat-treated cells, compared to that of the control cells. The decrease in SD activity following exposure to heat varied with the tissue. The SD activity decreased to a greater extent in the S-180 cells than in the normal tissues. In the normal tissues, the order of sensitivity to heat was stomach, spleen, large intestine, small intestine, esophagus, kidney and liver. These results show that hyperthermia is tissue selective, hence heat treatment of a malignant lesion should be carefully designed.

Animals↗
PubMed1989

Azo-dye-induced primary hepatoma and a gradual increase in thermosensitivity.

To determine whether or not the cytotoxic effects of hyperthermia are directed primarily to malignant cells, we examined changes in thermosensitivity during hepatocarcinogenesis in rats, as induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). The findings were compared with those in livers of rats fed a commercial diet. The cell viability was determined using the succinate dehydrogenase inhibition (SDI) test. The succinate dehydrogenase (SD) activity of liver cells, when exposed to heat (43 degrees C) for 2, 5, or 10 hr, decreased in a time-dependent manner, in each tissue. The decrease in SD activity was evident in 3'-Me-DAB liver for 5 hr of heat treatment on day 57, compared with findings in the normal liver. Significant differences were present for 2, 5, and 10 hr on days 93 and 136. Thus a chemically induced hepatoma is more sensitive to heat than are the normal cells. As this thermosensitivity gradually increased during the hepatocarcinogenesis, the malignant cells are particularly vulnerable to hyperthermia.

Animals↗
PubMed1989

Species differences in substrate specificity of pyrimidine nucleoside phosphorylase.

To compare the activity of pyrimidine nucleoside phosphorylase (PNP), an enzyme involved in the metabolism of 5-fluorouracil (5-FU), we used uridine (Urd), deoxyuridine (dUrd), and thymidine (dThd) as substrates and human, rat, and mouse neoplastic and normal tissues. As PNP activity was higher in the tumor tissues than in the normal ones in all species examined, the level of PNP activity is expected to be one critical factor linked to the effectiveness of 5-FU. In rats and mice, the ratio of the activities of Urd, dUrd, and dThd was about 10:7:1, whereas in humans, the ratio was 1:30:20. The main enzyme of PNP is Urd phosphorylase in rodents and dThd phosphorylase in humans. Therefore, when examining the metabolism of 5-FU and its analogues for potential clinical application, human tissues should be used.

Animals↗
PubMed1989

Hyperthermia enhances the in vitro activity of 1-hexylcarbamoyl-5-fluorouracil compared to that of 5-fluorouracil.

The synergic effects on HeLa cells between 1-hexylcarbamoyl-5-fluorouracil (HCFU), a lipophilic masked compound of 5-fluorouracil (5-FU), and hyperthermia were investigated, with the following results: (1) After the cells had been exposed to the drug at 77 microM for 1, 2 or 3 days, with or without heat (43 degrees C) for 2 h, treatment with HCFU and heat inhibited cell growth by 9.2% on day 3, compared to control cells, HCFU alone, heat alone or the combined treatment with 5-FU plus heat. (2) The cells were exposed to the drugs at 77 microM or heat (43 degrees C) for 15-45 min and the colonies counted on day 14. Combined treatment with HCFU plus heat inhibited the clonogenicity of HeLa cells to 22.4% of findings in the control cells and as compared to findings with other treatments. The combination of 5-FU, n-hexylamine and heat had much the same effect as the combined effect of the treatment of HCFU plus heat. (3) Intracellular levels of the drugs did not increase with hyperthermic treatment. Our findings suggest that it is the hexylcarbamoyl structure of HCFU that relates to the synergic effect between HCFU and hyperthermia. This combination is expected to have positive effects for treating patients with malignancy.

Antineoplastic Agents↗