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Biomedical subjects

Y Maehara

Publications and source records attributed to Y Maehara.

At least 271 records · Page 15Linked to original sources

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↗

Sensitivity to heat and radiation of human rectal malignant tissues in vitro.

The sensitivity to heat and radiation of 22 rectal cancer tissues obtained at biopsy was studied using the in vitro succinate dehydrogenase inhibition test. The succinate dehydrogenase activity of tissue fragments was assayed after exposure at 43 degrees C (hyperthermia) for 20 hours, to radiation of 6 Gy, and to both heat (43 degrees C) and radiation (6 Gy). The sensitivity to each treatment was estimated by the percentage of succinate dehydrogenase activity of the treated cells compared with that of control cells. The mean plus or minus standard deviation of succinate dehydrogenase activity after exposure to radiation, heat, and both heat and radiation, was 84.7 +/- 12.6 percent, 52.9 +/- 20.7 percent, and 46.8 +/- 20.7 percent, respectively. The succinate dehydrogenase activities of heat-treated cells and both heat- and radiation-treated cells were significantly lower than that of the radiation-treated cells (P less than 0.01). The succinate dehydrogenase activities of heat plus radiation treated cells were the lowest in tissues from cancer lesions. Although the number was small, there was a correlation between this test and clinical outcome in seven of nine cases. Thus, preoperative therapy of hyperthermia plus radiotherapy is expected to be effective for treating patients with rectal cancer.

Cell Survival↗

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↗

Combined treatment of adriamycin and dipyridamole inhibits lung metastasis of B16 melanoma cells in mice.

The combined effects of adriamycin (ADM) and dipyridamole (DP) on lung metastasis of B16 melanoma cells in mice were investigated. First, the antitumor effects of ADM and DP were examined both in vitro and in vivo. The clonogenicity of B16 melanoma cells was suppressed by the combination of ADM and the nontoxic dose of DP in vitro, and growth of the B16 melanoma solid tumor implanted subcutaneously in mice was inhibited with this drug combination, compared to findings with ADM alone in vivo. To examine events related to experimental lung metastasis, 2 X 10(5) B16 melanoma cells were given intravenously into the tail vein of mice and the efficacy was determined by counting the number of metastatic tumor nodules. DP in doses of 25-100 mg/kg given alone reduced the number of metastasis to about 85% that in the control group. ADM in doses of 1-4 mg/kg for 3 days inhibited the metastasis, in a dose-dependent manner. When combined with DP, the antimetastatic effect of ADM was enhanced and the number of metastasis prominently decreased, compared to single application of the drug (p less than 0.05). We speculate that ADM given concomitantly with DP may have the potential to inhibit metastatic growth of a tumor.

Animals↗

Adjuvant mitomycin-C prolongs survival time of patients undergoing extensive en bloc resection of carcinoma of the stomach invading the adjacent organs.

We retrospectively examined the long-term results of adjuvant chemotherapy with mitomycin-C (MMC) in 50 patients with gastric carcinoma invading the adjacent organs. All patients underwent gastrectomy and en bloc multiple resection of the invaded organs, with the intent of a potential cure. Evidence of direct invasion was confirmed histologically. These patients were classified into 3 groups, according to the dose schedule of MMC: 12 received prolonged, intermittent administration of the drug, in a total dose of 40 mg or more (group A); 19 were given a bolus injection at the time of surgery and/or on the following day, in a total dose of less than 40 mg (group B), and 19 were given no anticancer drugs (group C). These 3 groups were comparable with regard to various prognostic factors. The 5-year survival rates were 50, 32 and 17% in groups A, B and C, respectively. There was a statistical difference in survival between groups A and C (p less than 0.05). These results indicate that extensive en bloc resection plus intensive adjuvant chemotherapy prolong the survival time for those with gastric carcinoma invading the adjacent organs.

Antineoplastic Agents↗

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↗

[Four cases of an extramedullary plasmacytoma of the head and neck].

From 1987 to 1988, four patients with solitary, extramedullary plasmacytomas of the head and neck were seen at the Gunma Cancer Center Hospital. With reference to such plasmacytomas, we have reviewed the medical literature regarding these tumors and mainly present the results of radiation therapy with respect to these patients. One patient, who had a local recurrence after surgical treatment, underwent radiation therapy (36Gy in four weeks) that resulted in good local control of the disease. Two patients developed multiple painful bone lesions during their long follow-up periods without manifesting any abnormal laboratory findings, suggesting multiple myeloma. It was found that radiation therapy (less than 30 Gy) was useful for the palliation of painful lesions.

Combined Modality Therapy↗

Bioenergy status of human liver during and after warm ischemia.

Changes in the human liver's cellular bio-energy status during warm ischaemia and the subsequent blood reflow period were investigated by means of adenosine triphosphate (ATP) assay. In 8 patients, the average level of ATP in the liver tissue decreased significantly (p less than 0.05) from 28.7 +/- 8.6 mumol/g protein to 19.1 +/- 8.7 mumol/g protein within 10 minutes of warm ischemia. The pattern of decline in ATP levels did not correlate with clinical parameters, including presence of cirrhosis, liver function, type of ischemic method employed and postoperative complications. After reperfusion, ATP levels increased rapidly from 15.1 +/- 8.9 mumol/g protein to 19.6 +/- 8.2 mumol/g protein within 10 minutes, although the difference was not statistically significant. These patients' postoperative course was uneventful, and the results of serum chemistry tests were normal. The present study demonstrates a direct correlation between the levels of tissue ATP and the status of the liver's blood supply.

Adenosine Triphosphate↗

Correlation between hyperthermoradiosensitivity and clinical effect in carcinoma of the esophagus.

The correlation between hyperthermoradiosensitivity evaluated by an in vitro succinate dehydrogenase inhibition (SDI) test and the histopathologic effects of hyperthermochemoradiotherapy (HCR therapy) were investigated in 43 patients with carcinoma of the esophagus. The succinate dehydrogenase (SD) activity of tissue fragments taken at biopsy was assayed after exposure to heat (43 degrees C.) and radiation (6 grays) was done. The sensitivity to radiation plus heat treatment was estimated by the percentage of SD activity of the treated cells, compared with that of the control cells. The 43 patients were divided into three groups according to the degree of SD activity after exposure to radiation plus heat treatment. The SD activity was less than 50 per cent in group 1 (highly sensitive), between 50 and 70 per cent in group 2 (moderately sensitive), more than 70 per cent in group 3 (less sensitive). Eighteen of 20 in group 1, 11 of 17 in group 2 and two of six in group 3 were classified as being histopathologically "effective" for HCR therapy. The two year survival rate for groups 1, 2 and 3 were 55.5, 34.9 and zero per cent, respectively, while there were no statistical differences with regard to prognostic factors. These data suggest that in vitro activities of SD correlate well with the clinical effectiveness of HCR therapy. Therefore, it is recommended that a SD inhibition test be included among the guidelines for clinical management.

Adult↗

[Chemosensitivity testing of anticancer agents in head and neck tumors. I: Comparison between head and neck squamous cell cancers and thyroid cancers].

In vitro chemosensitivity was evaluated in 28 patients with head and neck squamous cell carcinomas (12 pharyngeal cancers, 7 oral cavity cancers, 4 laryngeal cancers, 4 maxillary sinus cancers and 1 esophageal cancer) and 19 patients with thyroid cancer. Tumor fragments obtained at biopsy or surgery were exposed to anticancer drugs and assayed for succinate dehydrogenase (SD) activity. The average of SD activity in squamous cell carcinomas was 63.2% for 5-FU, 24.6% for HCFU, 26.1% for CDDP, 41.0% for ADM, 28.4% for THP-ADM, 27.1% for ACR, 27.4% for CQ and 45.3% for VLB. In thyroid cancers, the average SD activity was 73.9% for 5-FU, 16.7% for HCFU, 32.6% for CDDP, 48.3% for ADM, 38.3% for THP-ADM, 57.3% for ACR, 39.0% for CQ and 75.3% for VLB. The SD activity inhibition rate by anticancer drugs was larger in cases of head and neck squamous cell carcinomas than in cases of thyroid cancers except for HCFU. Higher sensitivity to each antitumor drug detected in cancer tissues from metastatic lymph-nodes than in tissues from primary lesions needs further investigation.

Antineoplastic Agents↗

[In vitro chemosensitivity test: succinate dehydrogenase inhibition (SDI) test].

The succinate dehydrogenase inhibition (SDI) test was used for determining chemosensitivity of various human tumors. This test was based on the correlation between the cellular succinate dehydrogenase activity as determined by 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT), and cell viability. The chemosensitivity varied in the tissue. Some factors are involved in the chemosensitivity, that is origin of a tumor, tissue differentiation and tissue DNA synthetic activity. This test is a convenient method for clinical use and provides important information about chemosensitivity.

Drug Screening Assays, Antitumor↗

Cytophotometrically determined DNA content, mitotic activity, and lymph node metastasis in clinical gastric cancer.

Analyses of cytophotometrically determined DNA content and mitotic rate were carried out in 37 cases of gastric carcinoma to identify biologic significance of DNA abnormalities. Lymph node metastasis was also evaluated by DNA content and mitotic rate. According to the linear regression analysis, there were statistically significant correlations of mitotic rate with DNA variants such as the peak value, the mean value, and the frequency of cells with values exceeding tetraploid or hexaploid chromosome complement. There were significantly higher values for these DNA parameters in patients with lymph node metastasis compared with those without metastasis. Similarly, higher mitotic rates were observed in tumors with metastatic disease. Thus abnormal DNA fractions appear to be indicative of tumors with a high mitotic activity. The quantitative detection of the DNA abnormalities will provide pertinent biologic information required to predict the occurrence of metastasis in patients with gastric cancer.

Cytophotometry↗

[Prevention of peritoneal recurrence by combined intra-peritoneal and intra-tumoral injections of OK-432].

Protective effect of OK-432 on peritoneal recurrence was examined in an experimental mouse model with Meth A fibrosarcoma injected into both abdominal wall and intraperitoneal cavity. OK-432 was given through either intratumoral (i.t.), intradermal (i.d.), intraperitoneal (i.p.), or i.p. + i.t. route. A significant antitumor effect against abdominal tumor was observed in mice given i.t. or i.p. + i.t. injection of OK-432. A significant protective effect against peritoneal recurrence and prolonged survival time was obtained in an i.p. + i.t. group, although other treatment groups showed only minimal effect. We conclude that combined i.p. and i.t. administration of OK-432 may prevent peritoneal recurrence and lead to prolongation in clinical patients with advanced GI tract cancer.

Animals↗

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↗

Effect of glucocorticoid replacement on tumor growth after adrenalectomy in mice.

We studied the effects of glucocorticoid replacement on tumor growth after adrenalectomy of Meth A sarcoma in mice. Tumor growth was inhibited in the adrenalectomized mice when a minimum dose of corticosterone, 0.3 mg/day, was given for replacement, and higher doses led to an even greater inhibition. Corticosterone had no effect on tumor growth in the irradiated mice. Sinecomitant immunity in the case of growth of the retransplanted excised tumor was compromised in the adrenalectomized mice. In vivo neutralization and immunosuppressive activities were absent in the spleen cells of the adrenalectomized mice. It would thus appear that adrenalectomy suppresses tumor growth by mechanisms other than glucocorticoid ablation. For optimum tumor control, glucocorticoid replacement after adrenalectomy should be in excess of the minimum daily requirements.

Adrenalectomy↗

[Pleural thickening associated with solitary pulmonary nodule: evaluation with thin-slice CT].

Thin-slice CT was performed in 39 cases with a solitary pulmonary nodule abutting on the chest wall. Fifteen cases had bronchogenic carcinomas and the other 24 had benign non-neoplastic pulmonary nodules. CT findings were evaluated retrospectively paying special attention to the angle of the lesion with adjacent pleura, the homogeneity of the boundary between the lesion and the pleura, the configuration of the pleural thickening (broad or not, symmetric or not, tapering or not) and the visibility of the extrapleural fat plane. The broad, symmetric and tapering pleural thickening was seen in one of the 15 cases with a bronchogenic carcinoma and in 11 of the 24 cases with a benign non-neoplastic pulmonary nodule. Our result showed that the broad, symmetric and tapering pleural thickening might be indicative of benign pulmonary nodule. The authors concluded that thin-slice CT might be useful in the evaluation of the benignity of a solitary pulmonary nodule abutting on the chest wall.

Adult↗