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Biomedical subjects

Y Maehara

Publications and source records attributed to Y Maehara.

At least 217 records · Page 12Linked to original sources
PubMed1992

In vitro succinate dehydrogenase chemosensitivity of gastric carcinoma--relationship to DNA content.

Relationships between in vitro chemosensitivity and cell nuclear DNA content were investigated in malignant cells from 41 patients exhibiting advanced gastric carcinoma. The chemosensitivity was evaluated by measuring the succinate dehydrogenase (SD) activity in drug-exposed cancer cells and the DNA content was microspectrophotometrically determined. Following exposure of malignant tissue to carboquone (CQ) and cisplatin (DDP), the mean SD activity in cells displaying a relatively regular DNA distribution (type II) was significantly higher than that in those exhibiting a widely scattered DNA distribution (type IV; P less than 0.01 in CQ, P less than 0.05 in DDP). A similar tendency was recognized in cells that were treated with aclacinomycin A (ACR), Adriamycin (ADM), and mitomycin C (MMC). Such a decrease in SD activity in cells exhibiting a type IV pattern was remarkable, especially in cases undifferentiated adenocarcinoma. Mitotic counting analysis revealed a significantly higher value for DNA pattern type IV as compared with the findings for type II (P less than 0.01). These results demonstrate that gastric carcinoma displaying a high malignant potentially shows a better response to antitumor drugs. Adjuvant chemotherapy prescribed following drug-sensitivity testing should be effective against such tumors.

Adult↗
PubMed1992

Postoperative chemotherapy for patients with advanced gastric cancer.

The relationship between postoperative chemotherapy and survival time after gastric resection in patients with advanced gastric cancer was examined by retrospectively reviewing data on 916 patients treated in our clinics between 1965 and 1985. Of these patients, 738 were treated postoperatively with antitumor drugs. Postoperative chemotherapy was more often prescribed for those in the advanced stages of malignancy. Univariate analysis revealed that the survival time of patients given postoperative chemotherapy was shorter than for those not receiving chemotherapy, but there was no statistical significance. Multivariate analysis using the Cox regression analysis adjusted for sex, age, and other covariants indicated that operative curability, liver metastasis, serosal invasion, lymph node metastasis, peritoneal dissemination, and tumor size were the important prognostic factors. There was no correlation with postoperative chemotherapy. Our findings rule out any relationship between postoperative chemotherapy and length of survival time for patients with advanced gastric cancer undergoing gastric resection.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer.

The objective of the study was to define risk factors for peritoneal dissemination and haematogenous metastasis after curative resection of patients with an advanced gastric cancer. In retrospective analyses of 405 patients, 168 died of a tumour recurrence. Patients who died of gastric cancer were more likely to have large, invasive tumours which had spread throughout the stomach, metastasized to lymph nodes, and vessel invasion by gastric cancerous cells (P < 0.01 or P < 0.05). Of the 168 deaths, 60 (35.7%) were secondary to haematogenous recurrence, 53 (31.5%) were related to peritoneal dissemination, and 19 (11.3%) were related to a local recurrence. To determine the independent risk factors related to peritoneal dissemination and haematogenous metastasis, multivariate analyses using a stepwise logistic model suggested that serosal invasion (P < 0.01, relative risk = 2.57) and Borrmann type 4 (P < 0.01, relative risk = 1.95) were the greatest risk factors for peritoneal dissemination. The presence of lymph node metastasis (P < 0.01, relative risk = 2.62) and presence of vessel invasion by cancerous cells (P < 0.05, relative risk = 1.59) were the greatest risk factors for a haematogenous metastasis.

Cause of Death↗
PubMed1992

Early postoperative chemotherapy following noncurative resection for patients with advanced gastric cancer.

We studied the effect of early postoperative chemotherapy, including 5-fluorouracil (5-FU) for 5 days for patients with gastric cancer following noncurative resection. The study was prospectively randomised and controlled, and 162 (87.1%) of 186 were eligible candidates for statistical assessment. Patients randomised to group A received therapy that is used widely to treat patients with gastric cancer in Japan; mitomycin C (MMC), OK-432, UFT and PSK. Patients randomised to group B received the same drugs given to group A plus 5-FU bolus injections for 5 days, beginning on postoperative day 2. There were no differences in prognostic factors and doses of the drugs prescribed, except for 5-FU. There was no difference in the toxicity rate between the groups. Generalised Wilcoxon test revealed a P value of 0.169, and the 50% survival rate improved 1.4-fold in patients with gastric cancer treated with early postoperative chemotherapy of MMC, OK-432 plus 5-FU injection.

Aged↗
PubMed1992

Prognosis for surgically treated gastric cancer patients is poorer for women than men in all patients under age 50.

From 1965 to 1983, 1031 patients (689 men and 342 women) with advanced gastric cancer underwent gastric resection in our department. A retrospective study was done with special reference to the sex of the patients. The age, tumour size and location, Borrmann type, and histology were considered as the sex-related associations. The survival rate of women under age 50 years was lower than that of men, with a significant difference (P less than 0.01), and the 10-year survival rate was 39.2% for the men and 29.3% for the women. A multivariate analysis showed that the operative curability (relative risk: 2.11), lymph node metastasis (relative risk: 1.37), depth of invasion (relative risk: 1.30) and tumour size (relative risk: 1.05), all significant prognostic factors, differed between the men and women under age 50 years, and the survival rate for women was lower. Thus, early detection of gastric cancer is crucial to improve the survival of women under age 50 years. Postoperative chemotherapy may be considered for those with an advanced gastric cancer.

Adult↗
PubMed1992

Relationship between tumor histopathology and in vitro sensitivity to antitumor drugs in gastric cancer.

The in vitro drug sensitivity of gastric cancer tissues obtained from 40 patients with advanced cancer was compared in terms of the pathological classifications which were assigned according to the General Rules for the Gastric Cancer Study in Surgery and Pathology in Japan. Cases of poorly differentiated adenocarcinoma which had penetrated the serosa were evaluated using the succinate dehydrogenase inhibition (SDI) test for determining the in vitro chemosensitivity. The sensitivity of the stage III group to cisplatin was higher than that of the stage IV group. Although there were no statistical differences in drug sensitivities according to macroscopic findings (Borrmann's classification), the expanding growth type was more susceptible that the infiltrating type to cisplatin, aclacinomycin A (ACR) and carboquone (CQ) microscopically. In cases of lymph node metastasis [n(+)] the sensitivity to cisplatin, ACR, CQ, adriamycin and mitomycin C was less than in those with or without primary lymph node metastasis [n(-)]; lymphatic invasion in the gastric wall (ly) was a significant factor linked to drug resistance. Our findings indicate that the evaluation of tumor pathology is important in predicting the chemosensitivity of poorly differentiated gastric cancers.

Aclarubicin↗
PubMed1992

Metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil to 5-fluorouracil in partially hepatectomized rats.

Changes in the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in the plasma, lung, liver, stomach, small intestine, spleen and kidney in two-thirds partially hepatectomized rats. Concentrations of tegafur and 5-FU in plasma and tissues were determined 30 min after injecting 100 mg/kg of tegafur via the tail vein. The 5-FU concentration in the plasma remained unchanged for the first 7 days after hepatectomy. The tissue level of 5-FU was higher in the liver and kidney than in other organs examined, but there were no changes in levels of 5-FU in each organ examined. Our observations support the proposal that the conversion of tegafur to 5-FU is maintained in partially hepatectomized rats.

Animals↗
PubMed1992

Hyperthermo-radiosensitivity of esophageal cancer cells with high DNA ploidy in vitro.

The in vitro sensitivity to hyperthermia and radiation of esophageal cancer cells obtained from 50 patients was assayed by using the in vitro succinate dehydrogenase inhibition test, and the findings were correlated with data on DNA analysis. The DNA distribution patterns were grouped into types I, II, III and IV, according to the frequency of aneuploid cell populations. Esophageal cancer cells of high ploidy (type IV) had a lower sensitivity to radiation, however, a greater sensitivity to hyperthermia as compared to cells of low ploidy (type II). The sensitivity to hyperthermia was determined as positive in 2 of 8 for type II, in 7 of 25 for type III, and in 9 of 17 for type IV. In contrast, the positive sensitivity rates to radiation in type II, III, and IV were 25.0, 8.0, and 5.9%, respectively. When cells were exposed to combination of radiation with hyperthermia, the positive sensitivity rates increased in all groups (50.0, 44.0 and 70.6% in type II, III, and IV, respectively). There was a significant correlation between mean DNA values and the SD activities following exposure to heat treatment or radiation. These data, describing that cancer cells of high ploidy might have greater sensitivity to hyperthermia compared to radiation, indicate the clinical benefits of hyperthermia in cases of esophageal carcinoma, especially for patients with high DNA ploidy.

Adult↗
PubMed1992

Adriamycin combined with hyperthermia and dipyridamole is cytotoxic both in vitro and in vivo.

The cytotoxicity of adriamycin (ADM) combined with hyperthermia (Hyp) and/or dipyridamole (DP) was investigated using B16 melanoma cells in vitro and in vivo. When ADM was combined with Hyp at 43 degrees C or DP in a dose of 5 microM or with both, drug cytotoxicity enhanced the inhibition of colony formation and cell growth, and the effect was maximal when Hyp and DP were combined. Incubation with DP alone for 24 h, following ADM exposure, enhanced the toxicity even further (p less than 0.01). Measurement of intracellular levels of ADM in the B16 melanoma cells showed that Hyp and DP increased accumulation of ADM, and that DP, but not Hyp, significantly suppressed the ADM excretion (p less than 0.05). Growth of B16 melanoma implanted into subcutaneous tissue of the foot of C57BL mice was inhibited to a greater extent by the combination treatment of ADM and DP, ADM and Hyp, and also that of ADM, Hyp and DP, compared to the findings in cases of ADM or Hyp alone. As this trimodality treatment is effective both in vitro and in vivo, further study on possible clinical advantage is warranted.

Animals↗
PubMed1992

Cytotoxicity of mitomycin C and carboquone combined with hyperthermia against hypoxic tumor cells in vitro.

Enhancement of the cytotoxicity of mitomycin C (MMC) and carboquone (CQ) by hypoxia at elevated temperature was examined using the SDI test of mouse Sarcoma 180 and Ehrlich cells and clonogenic assay of HeLa cells. When Sarcoma 180 and Ehrlich cells were incubated at 43 degrees C for 2-10 h, the hyperthermic effect was enhanced by hypoxia. The succinate dehydrogenase activity of the cells was reduced by hyperthermia to a greater extent in the presence of hypoxia (O2:5%) than under conditions of aeration (O2:20%). When the cells were exposed to various concentrations of MMC and CQ, under hypoxia, activity of the drugs was enhanced compared to the findings under conditions of aeration. The enhancement was prominent in case of drugs and hyperthermia combined. Clonogenicity of hypoxic HeLa cells was also reduced to a greater extent with this combination than in case of aerated cells. We tentatively speculate that hyperthermo-chemotherapy using MMC and CQ has a potential to attack selectively hypoxic cells present in a solid tumor.

Aerobiosis↗
PubMed1992

Comparison of in vitro anticancer chemosensitivity between human squamous cell carcinoma and adenocarcinoma.

The chemosensitivities of squamous cell carcinoma (SCC) tissues from the head and neck area were compared to findings of adenocarcinoma, mainly from digestive organs. The sensitivity of each tissue was determined using the in vitro succinate dehydrogenase (SD) inhibition test, which shares a common principle with the 3-(4,5-dimethyl-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Tumor tissues were obtained at surgery or biopsy. Anticancer drugs tested were carboquone, Adriamycin, mitomycin C, cisplatin (CDDP), aclacinomycin A, 5-fluorouracil and 1-hexylcarbamoyl-5-fluorouracil with 10 times the peak plasma concentration, respectively. The means +/- standard deviations of SD activities in SCC tissues were significantly lower than those in adenocarcinoma tissues (p less than 0.001), and the sensitivity rates of SD activity in SCC tissues had a higher value than those in adenocarcinoma tissues (p less than 0.05), against each drug. Our study showed that CDDP-based combination regimens might be effective for SCC tissues. The chemosensitivity of each excised tissue should be tested, in order to prescribe sensitive, effective drugs for each patient.

Adenocarcinoma↗
PubMed1992

Hyperamylasemia associated with lymphadenectomy in patients surgically treated for gastric cancer.

The influence of standard lymphadenectomy on the occurrence of damage to the pancreas was evaluated in 28 patients with gastric cancer, by analysing related serum and urine enzyme activities, pre- and postoperatively. Enzymatic evidence for pancreatic damage was related to the surgical procedure performed. Postoperatively, the patients treated by R2 gastrectomy had significantly increased levels of P-type amylase in the serum compared with findings in patients treated by R1 gastrectomy or bypass procedures. Conversely, the S-type amylase in both groups remained within normal limits during the study period. Pancreatic secretary trypsin inhibitor (PSTI) and phospholipase A2 (PLA2) proved to be less sensitive to pancreas damage caused by lymphadenectomy. The R2 patients with P-type hyperamylasemia had no major postoperative complications. Thus, while the standard R2 gastrectomy may well be a relevant factor associated with the occurrence of transient P-type hyperamylasemia, there seems to be no relation to major postoperative complications such as pancreatitis.

Adult↗
PubMed1992

Trends in survival rates in Japanese patients with advanced carcinoma of the stomach.

From 1965 to 1985, 1,150 patients underwent gastrectomy for carcinoma of the stomach invading beyond the submucosa. One thousand, one hundred and forty-one patients were studied for five years or longer. The patients were classified into two groups--those treated from 1965 to 1974 (n = 622) and those treated from 1975 to 1985 (n = 519). In the more recent group, there was a significant increase in the number of patients more than 70 years of age, in the number of female patients, of carcinomas present in the upper two-thirds of the stomach, in tumors exceeding 10 centimeters and diffusely infiltrative type and in early cancer-simulating type of advanced carcinoma in gross appearance and in undifferentiated type adenocarcinomas in histology. Although differences in the incidence of patients treated by radical procedures, such as extensive lymph node dissection and combined resection of adjacent organs, were not statistically significant, the incidence for those who underwent total gastrectomy was significantly increased. The over-all long term survival rate remained unchanged during 1965 to 1985 (five year survival rate of 31.3 versus 32.8 per cent). However, there was a significantly longer survival period for patients who underwent total gastrectomy (five year survival rate of 22.9 versus 28.3 per cent) (p less than 0.05). Much of the improvement can be attributed to an increase in the detection of relatively small advanced carcinomas and of advanced carcinomas of the stomach simulating early carcinoma in the upper one-third of the stomach. Therefore, we emphasize the need to diagnose advanced carcinoma of the stomach when the lesion is in an earlier stage of disease.

Adenocarcinoma↗
PubMed1992

[Clinical significance of alpha(1----3)-L-fucosyltransferase activities in sera from patients with malignant diseases with a special reference to a potential tumor marker].

We measured alpha(1----3)-L-fucosyltransferase (alpha 13FT) activity in human plasma samples obtained from a group of 111 patients with malignant diseases, 86 patients with benign diseases, and 58 healthy controls using a newly developed assay method (Clin. Chem., 37: 2081-2086, 1991). The cutoff value was arbitrarily set at 73 units/ml (mean +/- 3SD of results for healthy controls). Forty-one of the 111 (36.9) plasma samples from patients with cancer showed high enzyme activity, and twelve of the 86 (13.6%) samples from patients with benign diseases were above the cutoff value. The levels of alpha 13FT were considerably high in samples obtained from the patients with esophagus, lung, liver and pancreatic and biliary cancer, and corresponding positive rates were 66.7, 64.7, 62.5 and 62.5%, respectively. The elevation of the enzyme activity was found in many samples from advanced cancer, whereas samples from patients with gastric and colon cancer in the clinical stage I showed high positive rates. No correlation was observed between the level of alpha 13FT and tumor--associated antigens such as carcinoembryonic antigen, CA19-9, and sialyl Tn (STN). These results suggest that alpha 13FT activity measured by the present assay method could have a potentiality for a new type of tumor marker.

Biomarkers, Tumor↗
PubMed1992

Gastric carcinoma invading muscularis propria and macroscopic appearance.

From 1965 to 1983, 1362 patients with primary gastric cancer and no other evidence of a malignancy underwent gastric resection in the Second Department of Surgery, Kyushu University. Of these, 117 patients (8.6%) with gastric cancer invading the muscularis propria (pm) were studied clinicopathologically with special reference to the macroscopic appearance: Borrmann type cancer or advanced gastric cancer simulating early gastric cancer (AGC simulating EGC). The Borrmann type cancer comprised 62.4% (73/117) of cases and the AGC simulating EGC comprised 37.6% (44/117). The survival rate for patients with the Borrmann type cancer was lower than in cases of AGC simulating EGC (P less than 0.01). The 10-year survival rate was 82.6% for patients with AGC simulating EGC and 60.5% for those with Borrmann type cancer. A multivariate analysis showed that operative curability and lymph node metastasis are significant prognostic factors and these events differed between the Borrmann type cancer and AGC simulating EGC and the survival rate for patients with the Borrmann type cancer was less favorable. Our findings show that the lymph node dissection is important for the operative curability of pm gastric cancer with the Borrmann type. Postoperative chemotherapy is required in cases of a non-curative resection.

Adult↗
PubMed1992

Resistance to anticancer drugs of well differentiated gastric adenocarcinoma with venous invasion.

A comparison of the chemosensitivity of well-differentiated human gastric cancer tissues was made between histological venous invasion positive (v(+)) and negative (v(-)) tissues, using the succinate dehydrogenase inhibition (SDI) test. These tissues obtained at the time of surgery were exposed to six anticancer drugs: carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP) and 5-fluorouracil (5-FU). Chemosensitivity was judged to be positive when the succinate dehydrogenase (SD) activity of the drug exposed cells decreased to below 50% of that of control cells. Decrease in the SD activity was more apparent in the v(-) tissues than in the v(+) tissues, exposed to the anticancer drugs and in particular to ADM (P less than 0.01), MMC (P less than 0.02) and DDP (P less than 0.05). The sensitivity rates to all six anticancer drugs were lower in the v(+) tissues. The resistance rates to all drugs tested were 0% in the v(-) tissues, but 21% in the v(+) tissues. In light of these observations, patients with gastric cancer of the well differentiated type and the histological venous invasion, will probably show a less positive response to cancer chemotherapy.

Adenocarcinoma↗
PubMed1992

Prediction of survival time after curative surgery for advanced gastric cancer.

This study was carried out to define independent prognostic factors influencing survival time and to examine the survival time of patients with advanced gastric cancer treated by curative resection. Six hundred and forty-eight patients were identified of whom 275 patients died of tumor recurrence during follow-up. Univariate analysis using Mantel-Cox analysis, indicated that tumor size, tumor location, gross appearance, degree of gastric wall invasion, lymph node metastasis and operative procedures were significant factors related to survival time (P less than 0.01 to P less than 0.05). Multivariate analysis using the Cox proportional hazard model adjusted for sex, age and other factors, suggested that tumor size (P less than 0.01, relative risk = 1.79), degree of gastric wall invasion (P less than 0.01, rr = 1.24) and lymph node metastasis (P less than 0.01, rr = 2.39) were the most independent prognostic factors statistically, although these three prognostic factors were inter-related. When the tumor is less than 5 cm and there is no serosal invasion or lymph node metastasis, then a longer survival time can be expected (88.7% at 5-years). If the tumor size exceeds 10 cm and there is invasion into neighboring structures and lymph node metastases, then survival time will be short (11.9% at 4-years).

Analysis of Variance↗