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Biomedical subjects

Y Maehara

Publications and source records attributed to Y Maehara.

At least 181 records · Page 10Linked to original sources
PubMed1993

Predictive value of preoperative serum sialyl Tn antigen levels in prognosis of patients with gastric cancer.

BACKGROUND: Expression of sialyl Tn antigen (STN) or serum STN levels were reported to be the independent prognostic factors of colon and ovarian cancers, respectively. The clinical significance of serum STN was evaluated as a tumor marker in gastric cancer. METHODS: Preoperative STN levels were examined in 350 patients with gastric cancer, surgically treated in the Department of Surgery II, Kyushu University Hospital, and in the National Kyushu Cancer Center, between April, 1981 and April, 1986. The patients were divided into two groups: a high STN group (n = 304), with over 45 U/ml of STN, and a low STN group (n = 46), with less than or equal to 45 U/ml. RESULTS: In the high STN group, the patients were older and the tumors were larger, compared to the low STN group. Histologically, tumors in the high STN group were deeply penetrating and the rates of lymphatic involvement, vascular involvement, and lymph node and hepatic metastases were higher. Infiltrative growth patterns dominated. Thus, the tumors were in an advanced stage. The 5-year survival rate for patients in the high STN group was significantly less than that of patients in the low STN group (44.8% +/- 7.9% versus 75.1% +/- 2.6%, P < 0.05). CONCLUSIONS: Because a high STN level correlates with an advanced tumor stage and a poorer prognosis, close follow-up and aggressive therapy are recommended.

Aged↗
PubMed1993

Laminin distribution patterns are closely related to liver metastasis in gastric cancer.

BACKGROUND: Laminin is the major glycoprotein of basement membrane and is known to have an important role in the metastatic process. METHODS: The authors used immunohistochemical techniques to evaluate the distribution of laminin-containing basement membrane in specimens from 157 patients with advanced gastric cancer. RESULTS: This membrane was found less frequently in the deep periphery than in the mucosa. According to our classification of distribution patterns, 39 (24.8%) tumors had laminin in the mucosa and the deep periphery of tumor (Group A); 37 (23.6%) tumors had laminin in the mucosa but not in the periphery (Group B); and in 81 (51.6%) tumors laminin was not found in the mucosa or the periphery (Group C). Tumors with laminin in the deep periphery (Group A) were characterized by expansive growth (P < 0.05), and there was a significant correlation with the occurrence of vessel invasion (P < 0.05) and liver metastasis (P < 0.01). Patients with Group A tumors had poor prognosis compared with patients with Group C tumors (P < 0.05). Multivariate logistic regression analysis showed laminin distribution patterns to be an independent value for predicting liver metastasis, as are lymph node involvement and expansive growth. CONCLUSION: The authors propose that laminin-positive basement membrane in the deep periphery in gastric cancer tissue is a significant risk factor for liver metastasis. For such high-risk patients, close follow up and postoperative adjuvant therapy are required.

Basement Membrane↗
PubMed1993

Diagnostic factors in gastric cardia cancer invading the esophagus.

BACKGROUND: The prognosis of patients with tumors in the upper one-third of the stomach, particularly those with esophageal invasion, is poor. METHODS: This study involved 168 patients with advanced cancer in the upper third of the stomach whose lesion had had invaded the esophagus. Clinical and pathologic studies were performed with respect to diagnostic factors and histologic differentiation of the lesion. RESULTS: Eighty-three patients (49.4%) had differentiated gastric cancer, and 85 (50.6%) had undifferentiated cancer. The survival time was shorter for patients with undifferentiated cancer than for those with differentiated cancer (P < 0.01). Multivariate analysis showed operative curability, liver metastasis, peritoneal dissemination, lymph node metastasis, serosal invasion, and tumor size to be independent prognostic factors. In patients with undifferentiated cancer, tumors were larger, serosal invasion was prominent, lymph node metastasis was present in 85.9% of cases, 64.7% of metastases were noncuratively resected, and survival time was less favorable. CONCLUSIONS: Our analysis shows that a group of patients at increased risk for tumor advancement will benefit from more aggressive therapy.

Adult↗
PubMed1993

A comparison of the logistic regression and the Cox proportional hazard models in retrospective studies on the prognosis of patients with gastric cancer.

To define the independent prognostic factors reducing survival time for gastric cancer, we compared the logistic regression and the Cox proportional hazard models applied to patients who underwent curative gastrectomy. All patients were evaluated after being followed for long fixed periods. Of 1,019, 269 (26.4%) died of tumor recurrence within a 5-year period and 36 (3.5%) died over 5 years after the original surgery. With regard to survival time, multivariate analyses using the Cox proportional hazard model in a stepwise manner adjusted for the sex, age, and 10 other factors, suggested that size of tumor (P < 0.01, relative risk [rr] = 1.0962), degree of gastric wall invasion (P < 0.01, rr < 1.3520), and status of lymph node metastasis (P < 0.01, rr = 1.6572) were the most independent prognostic factors. As well as, using the stepwise logistic regression model, size of tumor, (P < 0.01, odds ratio [or] = 1.115), degree of gastric wall invasion (P < 0.01, or = 1.428), and status of lymph node metastasis (P < 0.01, or = 2.182) were also the most independent risk factors for recurrence within 5 years after surgery. Although regression coefficients are not all the same, these three factors proved significant in both multivariate analyses. This equation for risk factors for prognosis is approached when searching for an appropriate method of retrospective studies using multivariate analyses.

Female↗
PubMed1993

Relationship between age and the time of surgery and prognosis after gastrectomy for gastric cancer.

We did a retrospective study to assess the influence of age on the prognosis in 1,537 patients with gastric cancer and who underwent gastrectomy. The patients were classified into 7 groups by age at the time of surgery, and the relative survival rates were calculated after correcting for each patient's sex, age, and the operative calendar year, based on the life table data for the general Japanese population. The overall prognoses in patients under age 30 and over age 80 years were poor (for ages under 30 years, 30-39, 40-49, 50-59, 60-69, 70-79, and over 80 years, the 5-year survival rates were 32.1%, 55.9%, 54.8%, 54.3%, 48.6%, 50.8%, and 31.5%, respectively). The poor prognoses in the youngest patients could be attributed to a high frequency of aggressive stage of the tumor. After curative gastrectomy, although the prognoses were excellent for every category in the first and second postoperative year, patients over age 80 years had a relatively poor prognosis after the third postoperative check-up. The poor prognoses in the oldest patients were attributed to the number of deaths due to other diseases. We conclude that for the very young or old subjects, age is a significant prognostic factor for those treated by gastrectomy for gastric cancer.

Adult↗
PubMed1993

Prognostic significance of tumor-host interaction in clinical gastric cancer: relationship between DNA ploidy and dendritic cell infiltration.

DNA ploidy of tumor cells and the degree of infiltration of dendritic cells were determined in 93 gastric cancer tissue specimens, and the mechanisms of tumor-host interaction on the prognosis were investigated. DNA ploidy patterns were grouped into low and high ploidy, and the degree of infiltration of dendritic cells (DC) was graded into marked and slight infiltration. In the low ploidy group, the 5-year survival rates in patients with marked and slight DC infiltration were 80.7% and 61.5%, respectively (P < 0.05). In the high ploidy group, however, there were no significant differences. In cases of low ploidy, the incidence of lymph node metastasis was significantly lower in the marked DC infiltration group compared with findings in the slight DC group. Thus, markedly infiltrating dendritic cells in gastric cancer tissue may lead to prolongation of survival time for patients with a carcinoma of the low ploidy profile, by preventing widespread nodal involvement.

Dendrites↗
PubMed1993

Prognosis for patients with carcinoma in the middle third of the stomach.

In 268 of the 1,115 patients (24.0%) with gastric cancer who underwent a curative resection in our clinics, the tumor was located in the middle third of the stomach. The clinicopathological features and prognosis of these patients were divided into two groups, according to site of the tumor: anterior wall (n = 58) vs. other sites (n = 210). Clinicopathological factors did not differ between the two groups. The survival time for patients with a tumor in the anterior group was shorter than that for patients with a tumor in other areas (P < 0.05). The five-year survival rate was 79.3% for patients with an anterior tumor and 91.9% for those with a tumor at a different site. A multivariate analysis indicated lymph node metastasis, serosal invasion, and anterior wall location to be independent prognostic factors indicative of a poor prognosis when the tumor was located in the middle third of the stomach. For such patients, close follow-up is needed to detect possible recurrences.

Female↗
PubMed1993

Effect of hyperthermia on the activity of 1-[(4'-hydroxy-2'-butenoxy)methyl]-2-nitroimidazole, which is cytotoxic to hypoxic cells.

The effect on EMT6/KU cells of a newly synthesized hypoxic cell sensitizer, 1-[(4'-hydroxy-2'-butenoxy)methyl]-2-nitroimidazole (RK28), combined with heat was determined in vitro under conditions of hypoxia. As compared with aerobic conditions, hypoxia produced a 1.30-fold increase in the cytotoxicity of the drug for mouse mammary EMT6/KU cells induced by 1 h heat treatment at 43 degrees C in medium with a normal pH. Hypoxia also reduced the surviving fraction of cells treated with both RK28 alone for 2 h and the same concentrations of RK28 and heat (43 degrees C) in combination. Those enhancement ratios corresponded to a 20.3- and > 345-fold increase, respectively. Moreover, concomitant treatment with RK28 and heat greatly inhibited the clonogenic activity of the EMT6/KU cells under conditions of in vitro hypoxia and in all experimental groups; there was a statistically significant difference in the time-response curves (P < 0.05). As hypoxic cells in a solid tumor are resistant to various anticancer drugs, RK28 combined with hyperthermia deserves further study for possible clinical applications.

Animals↗
PubMed1993

Postoperative PSK and OK-432 immunochemotherapy for patients with gastric cancer.

We evaluated the effects of chemotherapy given postoperatively with and without immunomodulators on the survival of patients who had undergone resection for gastric cancer. We conducted a retrospective survey of data on 963 Japanese patients treated at our department of surgery between 1965 and 1987. Data related to the duration of postoperative survival were calculated for those who received chemotherapy, i.e. an individualized combination of various agents given with or without the immunomodulators PSK, a protein extract of the fungus Coriolus versicolor, and/or OK-432, a preparation of an attenuated strain of Streptococcus (immunochemotherapy). Postoperative immunochemotherapy was more often prescribed for patients with advanced disease. The survival of patients who received immunochemotherapy was shorter than that of patients who received only chemotherapy. In a subgroup of patients adjusted for disease stage, the survival of those on chemotherapy versus immunochemotherapy did not differ significantly at any stage. For optimal results, a protocol for postoperative immunochemotherapy needs to be designed and investigated prospectively and according to the stage of gastric cancer. The stage III gastric cancers seem amenable to a favorable response.

Adjuvants, Immunologic↗
PubMed1993

Heat enhances the cytotoxicity of cis-diamminedichloroplatinum(II) and its analogues cis-1,1-cyclobutane-dicarboxylato(2R)-2-methyl-1,4- butanediammineplatinum(II) and cis-diammine(glycolato)platinum in vitro.

cis-1,1-Cyclobutanedicarboxylato(2R)-2-methyl-1,4-butanediammin eplatinum(II) (NK121) and cis-diammine(glycolato)platinum (254-S), analogues of cis-diamminedichloroplatinum (II) (CDDP) with reduced nephrotoxicity, are under clinical phase trial in Japan. Since CDDP has been shown to be more cytotoxic under conditions of an elevated temperature, we tested the cytotoxicity and cellular uptake of these analogues at 37 degrees and 43 degrees C using EMT6/KU cells in vitro. The cytotoxicity of CDDP was enhanced at 43 degrees C, and that of NK121 and 254-S was also enhanced, in a dose- and time-dependent manner. The 90% cytotoxic concentration (IC90) of each drug was reduced 2.9-fold for CDDP, 2.5-fold for NK121, and 2.2-fold for 254-S. Cytotoxicity was maximal when the two modalities were used simultaneously for all three drugs. The intracellular platinum concentration was assayed using flameless atomic absorption spectrophotometry. When exposed to IC90 drug concentration at 43 degrees C for 2 h simultaneously, the intracellular platinum concentration increased to 0.095 +/- 0.007 micrograms/10(7) cells (a 1.9-fold increase) for CDDP, to 0.198 +/- 0.012 micrograms/10(7) cells (a 1.3-fold increase) for NK121, and to 0.090 +/- 0.014 micrograms/10(7) cells (a 1.3-fold increase) for 254-S; respectively, as compared with the level measured after drug exposure at 37 degrees C (P < 0.05 for all drugs). The elevation in platinum concentration may be one of mechanism related to a synergistic effect of the two treatment modalities. The concomitant use of CDDP analogues and heat shows potential for possible clinical application.

Animals↗
PubMed1993

Gastric cancer with p53 overexpression has high potential for metastasising to lymph nodes.

Overexpression of the tumour suppressor gene p53 was investigated immunohistochemically in 96 primary gastric carcinomas and 26 corresponding metastatic perigastric lymph nodes. Abnormalities in p53 expression were found in 52 (54%) of the 96 primary carcinomas. Tumours stained positively for p53 frequently metastasised to lymph nodes (the metastatic rate: 85%) compared to findings in those with negative p53 staining (64%, P < 0.05). Ninety-two percent (24/26) of the malignant cells in the lymph nodes stained positively for p53. When the DNA ploidy pattern of the tumour was determined by flow cytometry, the aneuploid tumours in p53 positive and negative groups accounted for 69% and 45%, respectively (P < 0.05). Proliferative activity of the tumour, as measured by Ki-67 labelling, was significantly higher (30.6 +/- 12.0%) in the p53 positive group than that (25.1 +/- 10.7%) in the p53 negative group (P < 0.05). Thus, gastric cancer with a mutant p53 has high proliferative activity and metastasis to lymph nodes will probably occur.

DNA, Neoplasm↗
PubMed1993

Sequence dependence of the hyperthermic potentiation of carboplatin-induced cytotoxicity and intracellular platinum accumulation in HeLa cells.

We have examined the enhancement of cytotoxic effects of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) (carboplatin) by hyperthermia in HeLa cells using different regimes of timing and sequence. The results were compared with those obtained with cis-diamminedichloroplatinum(II) (cisplatin). We found that cisplatin simultaneously combined with heat was the most cytotoxic toward HeLa cells of the various timing and sequencing conditions studied. On the other hand, for carboplatin, drug treatment immediately following or during heat exposure showed the greatest effect. Intracellular platinum concentration in HeLa cells treated with heat before carboplatin showed a 2.75-fold increase over that in cells treated with the drug alone. The ratios for carboplatin given before, or during heating, were 0.67 and 1.42 respectively. Simultaneous exposure of cells to cisplatin and heat led to a 1.64-fold enhancement in cisplatin accumulation, compared to 0.92- and 1.24-fold increase for cells treated with cisplatin before and after heat respectively. Although each drug exposure prior to heat was less cytotoxic toward HeLa cells than any other heat/drug combination sequences, the platinum concentration was less than seen with each drug alone. Even though heat exposure prior to and during carboplatin showed a similar toxicity, platinum concentration in cells treated with heat prior to carboplatin was higher than that in cells treated with heat and carboplatin simultaneously. Thus, increased cytotoxicity cannot always be explained on the basis of intracellular platinum concentration. It is clear however that, differing from cisplatin, exposure of cells to heat prior to or during carboplatin administration results in the greatest cell kill.

Biological Transport↗
PubMed1993

Chemosensitivity testing of human mouth carcinoma cell line.

The chemosensitivity of KB cells derived from oral epidermal carcinoma to various antitumor agents was analyzed using the MTT[3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyl-2H tetrazolium bromide] assay. Optical density (OD) for MTT assay was measured with dual wavelengths. The chemosensitivity of the drugs was evaluated by the 50% OD (OD50) of each drug concentration in the control group. Five platinum (Pt) drugs and 3 anthracycline (AC) drugs were used in this study. The chemosensitivity differed among the 5 Pt drugs. No significant difference was observed among the 3 AC drugs. A linear increase in OD corresponding to an increase in number of cells was observed. When 0.1 M sodium succinate (S.S.) was added to 0.4% MTT, the sensitivity increased five-fold compared to the control group without S.S. The MTT assay is a precise, rapid, easy and inexpensive experimental system useful for evaluation of antitumor drug sensitivity on tumor cell lines.

Antibiotics, Antineoplastic↗
PubMed1993

The prognostic significance of proliferating cell nuclear antigen in clinical gastric cancer.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) is an intranuclear protein that is closely linked to the cell cycle. This antigen can be detected in formalin-fixed specimens. We studied the expression of PCNA in primary gastric cancer to identify its significance as a prognostic factor. METHODS: The avidin-biotin-peroxidase complex method was used for PCNA staining in sections from 138 patients with primary gastric cancer. All sections were formalin fixed and paraffin embedded. Two different sections were examined in each case. RESULTS: The PCNA labeling index (PCNA-positive cells/1000 cells x 100) varied from 7.0% to 59.7%. There were significant differences in tumor size, morphologic type, depth of tumor invasion, lymphatic permeation, vascular permeation, and lymph node metastasis between the high (> or = 33.4) and low (< 33.4) PCNA labeling index groups. The 5-year survival rates of the high and low PCNA labeling index groups were 5.8% and 66.2%, respectively, a significant difference (p < 0.001). Multivariate analysis showed that the PCNA labeling index was an independent prognostic factor for gastric cancer. CONCLUSIONS: Because PCNA immunostaining can be done in routine formalin-fixed paraffin-embedded sections, this could be a powerful tool for providing information about the prognosis of patients with gastric cancer.

Antigens, Neoplasm↗
PubMed1993

Early carcinoma of the stomach.

We analyzed data on 423 Japanese patients with early carcinoma of the stomach with respect to clinicopathologic features and prognosis. All patients were treated in the clinics at which we work. The upper one-third of the stomach was less frequently involved. Therefore, partial gastrectomy was performed more often in patients with early carcinoma of the stomach than in those with advanced carcinoma of the stomach. The differentiated type of carcinoma of the stomach was more frequent and grew expansively. Lymph node metastasis was noted in 11.6 percent of the patients, lymphatic vessel involvement was evident in 13.5 percent and extensive lymph node dissection (R2 or R3) was performed in 86.0 percent. The 15 year survival rate for patients with early carcinoma of the stomach was 89.0 percent. Lymph node metastasis, differentiated tumor type and patient age proved to be independent prognostic factors, as determined by multivariate analysis. Increased detection of early carcinoma of the stomach in its curable stages may be achieved through gastrointestinal series and endoscopy for symptomatic patients. A close follow-up evaluation is essential to detect recurrences, even when a curative resection is performed.

Female↗
PubMed1993

[Potentiation of cytotoxicity of anticancer drugs by flavone acetic acid].

We used B 16 melanoma cells both in vitro and in vivo to determine whether Flavone acetic acid (FAA) can increase the cytotoxicity of mitomycin C (MMC) under normothermic and hyperthermic (HT) conditions. The significantly increased cytotoxicity of MMC combined with FAA and HT seems to be mainly related to activation of alkylating species under FAA mediated hypoxic condition.

Animals↗
PubMed1993

Development of gastric cancer with special reference to growth and DNA content. Slow and rapid growing types.

We treated two patients with gastric cancer for whom surgery was delayed and the natural course of the tumor could be observed pre and postoperatively. A 70-year-old man with a well differentiated adenocarcinoma in the upper portion of the stomach underwent resection 6 years after the clinical diagnosis. Despite extension upwards towards the lower esophagus during a 6-year period, the tumor could be resected. In a poorly differentiated adenocarcinoma in the lower third of the stomach in a 40-year-old woman, the primary lesion was not distinct on the upper GI series done 6 months before, while at the time of laparotomy, disseminating metastases and pancreas invasion made it impossible to resect the stomach together with the tumor. The tumor in the man had a low DNA ploidy, while the lesion in the woman was characterized by a high ploidy. These findings show the distinct difference in the biological behavior of the tumor in these two patients. The possible correlation between DNA content with speed of growth warrants further attention.

Adenocarcinoma↗