Biomedical subjects

Y Maehara

Publications and source records attributed to Y Maehara.

At least 289 records · Page 16Linked to original sources

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

Adriamycin-induced DNA strand breaks in HeLa and in P388 leukaemia cells detected using in situ nick translation.

DNA strand breaks produced by adriamycin (ADR) were measured in HeLa cells and ADR-sensitive and -resistant P388 leukaemia cells, using the in situ nick translation method. The break sites in the DNA were translated artificially in the presence of Escherichia coli DNA polymerase I and 3H-labelled dTTP, and were visualized by autoradiographic observation of the grains. The DNA strand breaks in the HeLa cells increased in a dose-dependent manner, compared with findings in the untreated control cells, i.e., 15.2 fold at 20 micrograms/ml of ADR for 1 h. This level correlated with DNA single-strand breaks detected by the alkaline elution method. DNA breaks were also noted in the ADR-sensitive P388 cells, but in the ADR-resistant cells the level of DNA strand breaks was low. The enhanced cytotoxicity is apparently the consequence of the enhanced potential of ADR to cause breaks in the DNA strands. Our findings show that the survival response of the cells decreases and the level of DNA strand breaks increases following exposure to ADR. ADR resistance may be mediated by a reduction in the level of DNA strand breaks.

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↗

PubMed1989

Hypoxia enhances the lethality of mitomycin C and carboquone against human malignant tumor cells in vitro.

Solid tumors contain hypoxic cells which are relatively resistant to antineoplastic activity of radiation or to chemotherapeutic agents. We determined the increase in antineoplastic activities of mitomycin C (MMC) and carboquone (CQ) against human tumor cells under conditions of in vitro hypoxia, with the following results. (a) The HeLa cells had been exposed to various concentrations of MMC or CQ for 2 h under normally aerated (about 20%) or hypoxic conditions (5.0 and 0%) and were maintained under normally aerated conditions for 3 days. The succinate dehydrogenase activity was assayed, using the succinate dehydrogenase inhibition (SDI) test. Treatment with MMC or CQ reduced the SD activity, compared to findings in the control cells, under hypoxic conditions. (b) The cells were exposed to the drug, MMC or CQ, under normally aerated or anoxic conditions, for 15-45 min and the colonies counted on day 14. Treatment with 0.45 microM of MMC for 45 min inhibited the clonogenicity of HeLa cells by 25.4% of findings in the control cells under anoxia. Treatment with 0.03 microM of CQ for 30 min inhibited the clonogenicity by 41.5%. (c) The sensitivity of 14 human tumor tissues (6 gastric and 8 colorectal cancers) to MMC or CQ under hypoxic conditions was determined, using the SDI test. MMC and CQ showed hypoxic enhancement. Therefore, MMC and CQ have definite positive effects on hypoxic cells, and hence a higher therapeutic ratio for treating clinical solid tumors.

Azirines↗

PubMed1989

Succinate dehydrogenase inhibition test for evaluating head and neck tumors.

In vitro chemosensitivity was evaluated in human head and neck cancers using the succinate dehydrogenase (SD) test and the results were compared to findings in cases of malignant lymphomas and gastric cancers. Tumor fragments were exposed to several antitumor drugs at ten times the peak plasma concentration and assayed for SD activity. Decrease of SD activity was most prominent in the malignant lymphomas in cases of exposure to ADM, ACR, DDP, MMC and CQ; in which the average of SD activity decreased to below 30%. In the squamous cell carcinomas, SD activity below 40% was also observed with the same drugs, while the SD activity of gastric cancers was about 50%. There was a change of chemosensitivity following chemotherapy. The use of the SDI test will aid in selecting drugs for the prevention of recurrence or metastasis in head and neck cancers.

Antineoplastic Agents↗

PubMed1989

In vitro sensitivity of various human tumors to 1-beta-D-arabinofuranosylcytosine and N4-behenoyl-1-beta-D-arabinofuranosylcytosine.

The sensitivities to 1-beta-D-arabinofuranosylcytosine (ara-C) and N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC), a masked compound of ara-C, were determined in 33 human tumor tissues (11 gastric, 6 colorectal cancers and 16 malignant lymphomas), using the in vitro succinate dehydrogenase inhibition test. The succinate dehydrogenase (SD) activity of the tumor tissues was assayed following exposure to the drug at 8.8 or 88 microM for 3 days and the sensitivity was considered positive when the SD activity decreased to below 50% of that of the control cells at 88 microM. The SD activity decreased little at 8.8 microM and decreased individually at 88 microM. The mean of the SD activity at 88 microM was 65.7 +/- 11.5% for ara-C and 61.4 +/- 14.5% for BH-AC in gastrointestinal cancers, and 63.8 +/- 16.0% for ara-C and 58.3 +/- 18.3% for BH-AC in malignant lymphomas with a statistically significant difference (p less than 0.05). BH-AC is converted to ara-C for exertion of the cytotoxic effect and a positive correlation was noted between the SD activities of ara-C and BH-AC (r = 0.825 at 88 microM). The chemosensitivity varied with the tissue and 18% of the tissues were sensitive to ara-C, 27% to BH-AC and 15% were sensitive to BH-AC but resistant to ara-C. Our findings show that ara-C and BH-AC are equally cytostatic to human tumors. The sensitivity test of ara-C and BH-AC enables one to determine which drug is best suited for individual patients.

Antineoplastic Agents↗

PubMed1989

[Detection of cellular DNA strand breaks induced by antitumor drug and heat using in situ nick translation].

Cellular DNA strand break induced by an alkylating agent: Carboquone (CQ), and heat (43 degrees C) was detected in HeLa cells in vitro and mouse sarcoma-180 cells in vivo. The break sites in the DNA were translated artificially in the presence of Escherichia coli DNA polymerase I and [3H]-labeled dTTP and sites in the DNA were visualized by autoradiographic observation of grains in the nuclei. These breaks increased in a dose and time dependent manner, compared to findings in the control cells. Our findings show that the surviving response of cells decreases while the level of DNA strand breaks increases following exposure to CQ or heat. The nick translation method is a rapid in situ assay for determining drug and heat induced DNA damage of tumor cells, under in vitro and in vivo conditions and in a semi-quantitative manner.

Azirines↗

PubMed1989

[Three cases of retroperitoneal cystic lymphangioma].

Retroperitoneal cystic lymphangioma is a rare benign tumor. Three cases of retroperitoneal cystic lymphangioma with histological proof were reported. Every case revealed similar characteristic appearances on CT, such as 1. unilocular or multilocular cystic mass with homogeneous near-water density, 2. non-enhanced or slightly enhanced wall and septum, 3. commonly thin wall without irregularity, 4. compression of surrounding organs with sharp margin. No secondary changes such as hydronephrosis and ischemic change were noted in the surrounding compressed organs, revealing that this tumor is soft and the growth is slow. Several differential diagnoses were considered, but diagnosis was not so difficult on CT, considering anatomical relations and clinical appearances.

Adult↗

PubMed1989

Nick translation detection in situ of cellular DNA strand break induced by radiation.

DNA strand break in HeLa cells induced by radiation was detected using the in situ nick translation method. The cells were exposed to radiation of 3, 6, 12, 18, and 24 Gy in Lab-Tek tissue culture chamber/slides and were fixed with ethanol/acetic acid on the slide glass. The break sites in DNA were translated artificially in the presence of Escherichia coli DNA polymerase I and [3H]-labeled dTTP. Autoradiographic observation was made of the level of break sites in the DNA. The DNA strand break appeared even with a 3 Gy exposure, increased 8.6 times at 24 Gy compared with the control cells, and this level correlated reciprocally to change in cell viability. This nick translation method provides a rapid in situ assay for determining radiation-induced DNA damage of cultured cells, in a semi-quantitative manner.

Animals↗

PubMed1989

[Phase II clinical study of LC9018 on carcinomatous peritonitis of gastric cancer. Subgroup for Carcinomatous Peritonitis, Cooperative, Study Group of LC9018].

Using patients with carcinomatous peritonitis caused by gastric cancer, we conducted a Phase II clinical study of LC 9018 by administering the agent alone or in combination with mitomycin C (MMC). Out of 29 patients enrolled, 12 were treated with LC 9018 alone and 17 others with LC 9018 + MMC. Of these, 15 cases were found completely evaluable. The response rate for 15 complete cases against carcinomatous peritonitis was 60.0% (3/5) for the group treated with LC9018 alone and 70.0% (7/10) with LC9018 + MMC. Of the 27 eligible patients, the ascites could be controlled in 58.3% (7/12) for those treated with LC9018 alone and 60.0% (9/15) for those with LC9018 + MMC, with tumor cells being eliminated in 50.0% (6/12) and 60.0% (9/15), respectively. Major adverse reactions included fever, nausea/vomiting, abdominal pain and increases in GOT and GPT. These findings suggest that LC9018 might be a useful therapeutic agent against carcinomatous peritonitis of gastric cancer whether used alone or in combination with MMC.

Adjuvants, Immunologic↗

PubMed1989

[Hyperthermo-chemo-radiotherapy of patients with carcinoma of the esophagus and prediction of the clinical remedial value using the in vitro succinate dehydrogenase inhibition test].

Hyperthermia combined with irradiation and chemotherapy was prescribed for patients with resectable (n = 88) and unresectable (n = 36) carcinoma of the esophagus. The histopathological effectiveness, and the long term results were compared between two groups of patients treated with hyperthermo-chemo-radiotherapy (HCR therapy) and those treated with chemoradiotherapy (CR therapy). A correlation between the hyperthermia sensitivity test, using the in vitro succinate dehydrogenase inhibition test, and the clinical remedial value was also examined in malignant tissues from 47 patients with esophageal cancer, and treated with HCR therapy. In the resected cases, preoperative HCR therapy resulted in a significantly higher histopathological effectiveness rate (69%) compared with that in cases treated by CR therapy (48%) (P less than 0.05). The long term results of patients with both resectable and unresectable carcinoma, given HCR therapy were significantly better than those given CR therapy (P less than 0.05). On the other hand, the clinical remedial value, determined radiographically showed a correlation rate of 77% to the hyperthermia sensitivity test. Thus, the HCR therapy resulted in not only a higher histopathological effectiveness rate but also a significantly longer survival without severe side effects, and this hyperthermia sensitivity test using the succinate dehydrogenase inhibition test facilitates prediction of the outcome of the HCR therapy.

Antineoplastic Agents↗

PubMed1989

[Autopsy findings in 255 cases of head and neck cancer].

Two hundred and fifty-five autopsies of patients with head and neck cancers were performed at Gunma Cancer Center between 1972 and 1986. This figure accounts for 27.8% of the total number of autopsies at the Center which was 917 cases during the period. The autopsies discussed are as follows: 1) Fifty-five cases (21.6%) were oral carcinomas, 43 cases (16.9%) maxillary carcinomas, 39 cases (15.3%) laryngeal carcinomas, 32 cases (12.5%) hypopharyngeal carcinomas and finally 22 cases (8.6%) of malignant lymphomas. 2) The incidence of visceral metastases in 200 cases of squamous cell carcinoma numbered 83, including 70 cases (84.3%) of lung metastases, the most frequently observed. 3) The causes of death in head and neck cancer were primarily of two types: Twenty five cases were due to major hemorrhage as a result of carotid rupture owing to tumor invasion and its intensive irradiation. The remaining 14 deaths resulted from interstitial pneumonitis occurring during bleomycin systemic chemotherapy. The brevity of survival from the onset of symptoms would seem to indicate that, by the time head and neck cancer manifest themselves clinically, they are already at a astage of development beyond the scope of treatment.

Autopsy↗

PubMed1989

[Perioperative management of cesarean section in a patient pregnant with twins complicated by hyperthyroidism].

A 30-year-old twin pregnant woman complicated with hyperthyroidism was scheduled to receive anesthesia for cesarean section. During the early months of pregnancy, her thyroid status was stimulated, being positive for TSH-binding inhibitor immunoglobulins (TBII). Because maternal positiveness of TBII correlates with neonatal hyperthyroidism, she was treated with antithyroid drugs (methimazole). Her thyroid status was suppressed gradually and her TBII level became negative. On the 38th week of pregnancy, she underwent cesarean section by lumbar spinal anesthesia and twin girls were delivered with Apgar scores of 9. The thyroid statuses of the twins were measured, showing that their thyroid functions to be almost equal, although they were dizygotic twins. T3 and free-T3 were below the normal limits for adults, but they did not require any therapy. Maternal level of TBII is considered to be a useful index for management of patients with hyperthyroidism during the perianesthetic period for cesarean section. In this type of patients the thyroid status of both the mother and fetus should be carefully followed.

Adult↗

PubMed1989

[The effectiveness of radiation therapy in bone metastasis from breast cancer].

48 cases with bone metastasis from breast cancer were treated by radiation therapy. Result; 1) The effective ratio of radiation therapy on symptomatic relief of pain was 83%. 2) In 90% of effective cases, patients felt pain relief at 20 Gy. 3) For 3 of 7 cases which showed paralysis by vertebral metastasis, radiotherapy was very effective. 4) The patients with only bone metastasis have good prognosis. So, it is important radiotherapy is performed on different outlook.

Adult↗