Biomedical subjects

Y Maehara

Publications and source records attributed to Y Maehara.

At least 163 records · Page 9Linked to original sources

PubMed1995

[Biological features determining the chemosensitivity of gastric cancer].

We analysed the relationship between several biological properties of gastric cancers and their chemosensitivity determined by MTT assay. Higher chemosensitivity was associated with poor differentiation, aneuploidy, and higher proliferative activity. Lymph node metastasis was more chemosensitive than primary lesion, while liver metastasis was less. Gastric cancer expressing multidrug-resistance associated protein (MRP) showed lower sensitivity to several anticancer drugs, including adriamycin and etoposide. p53 status and susceptibility to apoptosis were also associated with chemosensitivity. Thus, chemosensitivity of clinical gastric cancer might be increased if these characters can be modified by some new biologic therapy.

Antineoplastic Agents↗

PubMed1994

Expression of glutathione S-transferase-pi and sensitivity of human gastric cancer cells to cisplatin.

BACKGROUND: The authors examined the correlation between the expression of glutathione S-transferase-pi (GST pi) and the sensitivity of gastric cancer to anticancer agents. METHODS: In 62 human gastric carcinomas, the expression of GST pi was immunohistochemically evaluated, and sensitivity to the anticancer drugs, cisplatin (CDDP), doxorubicin (DXR) aclacinomycin A (aclarubicin), (ACR), 5-fluorouracil (5-FU), mitomycin C (MMC) and carboquone (carbazilquinon) (CQ) was examined using the in vitro succinate dehydrogenase inhibition test. The authors used the Chinese hamster ovary (CHO) cell line and its variant CDDP-resistant cell line C/CDP-2, and they analyzed the relationship among CDDP-sensitivity, mRNA expression, and immunohistochemical staining. RESULTS: Immunohistochemically detected GST-pi-positive tumors were noted in 35 of 62 excised tumors. There was no significant correlation between GST-pi expression and clinicopathologic features or prognosis. The succinate dehydrogenase activity of each drug for tumors, with regard to negative or positive GST-pi, was 34.9 plus or minus 13.7% and 46.0 plus or minus 22.0% for CDDP, with a significant statistical difference (P < 0.05). However, there was no statistical difference for the other drugs tested. C/CDP-2 cells showed a lower sensitivity to CDDP, a higher expression of mRNA for GST pi and a stronger immunohistochemical staining than CHO cells. CONCLUSIONS: The overexpression of GST-pi is significantly related to the sensitivity of gastric cancer to CDDP.

Aclarubicin↗

PubMed1994

Prognostic significance of the number of positive lymph nodes in gastric carcinoma.

A total of 195 patients with node-positive gastric carcinoma who were treated by curative gastrectomy and lymphadenectomy were studied to evaluate the prognostic significance of the number of metastatic lymph nodes. Univariate analysis showed that the number and level of positive nodes, tumour size and depth of invasion, and type of gastrectomy were significantly related to patient survival. Multivariate analysis indicated that the number of positive nodes (up to six versus seven or more; relative risk 2.91), depth of invasion (three levels; relative risk 1.83) and histological type (well versus poorly differentiated; relative risk 0.63) were independently correlated with survival. The results indicate that the total number of positive nodes is the most significant prognostic factor in patients with node-positive gastric carcinoma.

Adenocarcinoma↗

PubMed1994

Growth pattern and prognosis of gastric cancer invading the subserosa.

Gastric cancer invading the subserosa with infiltrative growth was classified as part of the serosal invasion group and named prognostic serosal invasion positive [ps(+)] histologically. We analyzed clinicopathological features and prognosis of 166 Japanese patients with gastric cancer invading the subserosa, according to the growth pattern. All patients were treated in the Department of Surgery II, Kyushu University. Patients with infiltrative growth (ss gamma) were younger and their tumors were frequently undifferentiated compared to findings in those with noninfiltrative growth: expansive (ss alpha) and intermediate growth (ss beta). There was no difference in any other clinicopathological characteristic between those with infiltrative and noninfiltrative growth tumors. The 10-year survival rate was 66.7% for the infiltrative type and 54.2% for the noninfiltrative type, with no statistically significant difference. Lymph node metastasis, curative resection, and extended lymph node dissection, but not growth pattern, proved to be independent prognostic factors, as determined by multivariate analysis. Our findings suggest that it is not the growth pattern which affects the prognosis of ss cancers. Extensive lymph node dissection should be done when lymph node metastasis is present.

Adult↗

PubMed1994

Role of intraoperative assessment of lymph node metastasis and serosal invasion in patients with gastric cancer.

The clinical diagnoses of nodal status (N) and tumor invasion (T) were performed intraoperatively during 1499 consecutive operations for gastric carcinoma and compared with subsequent pathologic diagnoses. An accurate macroscopic diagnosis of N stage was difficult; overall accuracy was only 56.6%. Intraoperative assessment of T stage (particularly of serosal invasion) was correct for 93.2% of early stages of the disease with invasion confined to the mucosa or submucosa (pT1) when the pathologist assessed the T stage in the resected specimen, for 95.6% of advanced tumors invading the serosa (pT3), but for tumors of an intermediate stage with invasion involving the muscularis propria or the subserosa (pT2) in only 41.9% of cases. Macroscopic overestimation occurred in 58.1% of cases with pT2 tumors, which were characterized by carcinomas in the upper third of the stomach, tumors larger than 5 cm, carcinomas of the ulcerating type, differentiated adenocarcinomas, tumors invading the subserosa, and those accompanied by lymph node metastasis or liver metastasis. The overestimated group had a significantly poorer prognosis than the correctly assessed cases (P < 0.05). Since multivariate logistic regression analysis showed that the significant risk factor related to the inaccurate intraoperative assessment of T stage was tumor size, the error in diagnosis may correlate with a greater degree of tumor spread. Surgeons should decide their therapeutic approach at the time of surgery on the basis of their intraoperative assessment of tumor spread. We recommend extensive surgery followed by adequate chemotherapy when serosal invasion is suspected at surgery.

Adenocarcinoma↗

PubMed1994

Postoperative chemotherapy including intraperitoneal and intradermal administration of the streptococcal preparation OK-432 for patients with gastric cancer and peritoneal dissemination: a prospective randomized study.

We studied the effects on survival time of postoperative immuno-chemotherapy, including the streptococcal preparation OK-432, in patients with gastric cancer and synchronous peritoneal dissemination. The patients were prospectively randomized and a valid statistical assessment could be made for 109. Patients randomized to group B received therapy that is widely used in Japan to treat patients with gastric cancer: mitomycin C (MMC) and UFT, a combination of tegafur and uracil in a molar ratio of 1:4, for 1 year. Patients randomized to group A received the same drugs as were given to group B patients plus OK-432 i.p. for 7 days, beginning on postoperative day 0, and OK-432 by intradermal injection for 1 year, at 2-week intervals. There were no differences between the two groups in any known prognostic factor or in the dose of any drug administered except for OK-432. There was no difference in the toxicity rate between the groups. In this negative trial, there was no improvement in survival time with the addition of OK-432 to MMC and UFT for patients with gastric cancer and peritoneal dissemination.

Aged↗

PubMed1994

Laser flow cytometric studies on the intracellular accumulation of anthracyclines when combined with heat.

The effects of heat on intracellular accumulation of anthracyclines were investigated by laser flow cytometry analysis. Sarcoma-180 cells were exposed to Adriamycin (ADM), epirubicin (EPIR), daunomycin (DM), THP-Adriamycin (THP), ME-2303 (ME) and KRN-8602 (KRN) at 37 degrees C and at higher temperatures. There was a dose-dependent increase in the fluorescence intensity of all drugs at 37 degrees C, but heat varied the fluorescence intensity of each drug. At 43 degrees C the cellular fluorescence of ADM and EPIR increased by approximately 200%, but for DM the increase was 110-130%. The cellular fluorescence of THP and ME was little affected by heat, and heat reduced that of KRN to 80-90%. Each drug showed was unique in the relationship between drug exposure time and the fluorescence intensity at 37 degrees C and 43 degrees C. Cytotoxicity determined by the MTT assay was enhanced with heat in the cases of ADM and EPIR, but not with DM, THP, ME, or KRN. Thus, ADM and EPIR are expected to show enhanced antitumor activities when given in combination with hyperthermia.

Animals↗

PubMed1994

Effect of gastrectomy on the pharmacokinetics of tegafur, uracil, and 5-fluorouracil after oral administration of a 1:4 tegafur and uracil combination.

The effects of gastrectomy on the pharmacokinetics of UFT, a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, were examined in 26 patients with macroscopic Stage I gastric cancer. In all, 200 mg UFT (in terms of tegafur) was given to 17 patients who underwent partial gastrectomy (9 cases of Billroth I reconstruction, 8 cases of Billroth II reconstruction) and to 9 patients who underwent total gastrectomy with modified Roux-en-Y reconstruction. Before the operation, the area under the curve (AUC) for tegafur, uracil, and 5-fluorouracil (5-FU) was 79.28 +/- 26.88, 4.41 +/- 1.78, and 0.51 +/- 0.20 micrograms h ml-1, respectively. Partial (Billroth I and II) and total gastrectomy did not alter the AUC of tegafur, and partial gastrectomy using the Billroth I and II methods decreased the AUCs of uracil and 5-FU during the first 2 weeks postoperation. However, plasma levels of uracil and 5-FU reverted to preoperative values at 3 months postsurgery. Our findings show that when UFT is prescribed for patients treated in the early postoperative period following partial gastrectomy for cancer, dose increases and the timing of administration should be given close attention.

Administration, Oral↗

PubMed1994

Postoperative immunochemotherapy including streptococcal lysate OK-432 is effective for patients with gastric cancer and serosal invasion.

The effects of postoperative immunochemotherapy including the streptococcal preparation OK-432 on the rate of peritoneal recurrence and survival time after curative resection were studied in 36 patients with gastric cancer. Patients randomized to group B received 18 months of a therapy that is widely used in Japan for patients with gastric cancer: mitomycin C (MMC) and UFT, a combination of tegafur and uracil in a molar ratio of 1:4. Patients randomized to group A received the same drugs given to group B plus an intraperitoneal injection of OK-432 on postoperative day 0 and intradermal injections of OK-432 for 18 months at 2-week intervals. There were no differences between the two groups in any known prognostic factor or dose of any drug received, except for OK-432. There was no difference in the toxicity rates between the groups. The concomitant administration OK-432 and anticancer drugs significantly decreased the rates of peritoneal recurrence and lengthened survival time (P < 0.05).

Adjuvants, Immunologic↗

PubMed1994

Proliferative activity as a prognostic factor in Borrmann type 4 gastric carcinoma.

Proliferative activities in 181 primary Borrmann type 4 gastric carcinomas were investigated using percentage labelling of proliferating cell nuclear antigen (PCNA) and an argyrophilic nucleolar organiser region (AgNOR) count. Tumours with a high proliferative activity often metastasised to lymph nodes (P < 0.01), and these patients had a lower survival rate (P < 0.05). A significant correlation was recognised between the PCNA labelling percentage and AgNOR count (r = 0.452, P < 0.001). Cox's regression analysis showed that PCNA labelling percentage is an independent prognostic factor. These results indicate that estimating proliferative activity may be useful in predicting lymph node metastasis and patients' prognosis in cases of Borrmann type 4 gastric carcinoma.

Adenocarcinoma↗

PubMed1994

Combined evaluation of preoperative serum sialyl-Tn antigen and carcinoembryonic antigen levels is prognostic for gastric cancer patients.

We have found that elevation of preoperative serum sialyl-Tn antigen (STN) levels is associated with a poor prognosis for gastric cancer patients, and these high levels remain in the advanced stage of the disease. We have now examined findings with the combined assay of STN and carcinoembryonic antigen (CEA) levels with regard to prediction of the prognosis of gastric cancer patients. Serum CEA levels and STN levels were determined preoperatively in 349 Japanese patients with gastric cancer. The patients were divided into four groups: (A) the CEA (-) STN (-) group (CEA < or = 5 ng ml-1, STN < or = 45 U ml-1, n = 286); (B) the CEA (-) STN (+) group (CEA < or = 5 ng ml-1, STN > 45 U ml-1, n = 31); (C) the CEA (+) STN (-) group (CEA > 5 ng ml-1, STN < or = 45 U ml-1, n = 17); and (D) the CEA (+) STN (+) group (CEA > 5 ng ml-1, STN > 45 U ml-1, n = 15). Clinicopathological features and the prognosis of these groups were examined. The distribution of two markers showed no significant correlation. The patients in the CEA (+) STN (+) group (group D) had more advanced disease than the patients in CEA (-) STN (-) group (group A); tumour size was larger, serosal invasion was prominent, lymphatic and vascular involvement was frequent and the tumour was more infiltrative. Lymph node metastasis and hepatic metastasis were more common. Total gastrectomy was usually performed, and the non-curative rate was higher. The 5-year survival of patients in the CEA (+) STN (+) (group D) was 14.5 +/- 9.5%, that is lower than that of patients in any other group [CEA (+) STN (-) (group C) 44.1 +/- 12.7% (P < 0.05); CEA (-) STN (+) (group B) 60.1 +/- 9.5% (P > 0.05); CEA (-) STN (-) (group A) 77.6 +/- 9.5% (P < 0.05)]. This combined assay of these markers will aid in estimating the prognosis and selecting appropriate drugs and care for gastric cancer patients.

Aged↗

PubMed1994

Dukes's classification: a valid prognostic indicator for gastric cancer.

Dukes's classification for colorectal cancer is simple, and correlates well with survival. This study assessed whether the principles of Dukes's classification applied to gastric cancer resulted in the separation of prognostically useful groups. The cumulative survival curves determined by Dukes's, Astler-Coller's (another classification for colorectal cancer), and the Japanese classification for gastric cancer were evaluated using 476 curatively treated patients with gastric cancer. Of the three staging systems, both Dukes's and the Japanese classifications showed a step-wise relationship between the stage of the tumour and the survival of patients. The prognostic value of Dukes's classification was reinforced when Dukes's C cases were subdivided according to the number of positive nodes (1-6 v > or = 7) or the level of positive nodes (n1 v n2,n3) but not when the subdivision was made according to the depth of wall invasion. A modified Dukes's classification in which Dukes's cases are subdivided according to the number of metastatic nodes (Dukes's Ca = 1-6 nodes, Dukes's Cb > 6 nodes) could be both simply and accurately applied to gastric cancer.

Evaluation Studies as Topic↗

PubMed1994

A case of posttherapeutic sclerotic change of bone metastasis from renal cell carcinoma which proved histopathologically to be complete response.

A 60-year-old man with renal cell carcinoma and metastases to the right 7th rib and L2 vertebra (T2N0M1, OSS) was treated with interferon-alpha and the uracil and tegafur combination following nephrectomy. One and a half years later on bone scintigraphy, the abnormal accumulation had disappeared at the L2 vertebra and weakened in its intensity at the right 7th rib. Plain X-ray revealed that the metastatic lesion at the right 7th rib had decreased in size and had been replaced by calcification. The right 7th rib was removed surgically and step-sectioned pathological specimens revealed necrosis with no viable cancer cells.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Role of lymph node dissection and splenectomy in node-positive gastric carcinoma.

BACKGROUND: In gastric carcinoma the relationship between survival of patients and degree of lymph node dissection is still controversial and there is no agreement about the efficacy of extended lymph node dissection and splenectomy. METHODS: Long-term results after surgery were statistically analyzed in 240 patients who underwent curative gastrectomy with lymph node dissection for node-positive gastric carcinoma from 1975 to 1990. RESULTS: The survival of patients was not significantly different among R1, R2, and R3 dissections, with the 10-year survival rate being 57%, 50%, and 44%, respectively. The survival rate was also not different between R2 and R3, even when the cases were stratified by the level of lymph node metastasis (N1, 66% vs 58%; N2, 28% vs 31%). The survival of patients was not significantly different between cases treated without splenectomy and those treated with splenectomy, with 10-year survival rates being 47% and 26%, respectively. The survival rate was also not different between non-splenectomy- and splenectomy-treated cases, even when the patients were compared in the same level of lymph node metastasis (N1, 60% vs 45%; N2, 23% vs 11%). CONCLUSIONS: In cases of curative gastrectomy the survival time of patients was not influenced by the level of lymph node dissection and splenectomy. For the treatment of node-positive gastric carcinoma (N1, N2) the long-term efficacy of R3 dissection and splenectomy seems limited.

Female↗

PubMed1994

[Intra-arterial combination chemotherapy using both regimen selected by chemosensitivity test and caffeine to increase effect for osteosarcoma in extremity].

We treated three patients with osteosarcoma in extremity with intra-arterial combination chemotherapy using a regimen selected by succinate dehydrogenase inhibition chemosensitivity test, and used caffeine to enhance its effect. In two patients with osteosarcoma in distal diametaphysis of the radius and extraskeletal osteosarcoma in sole of the foot, the effect of intra-arterial combination chemotherapy was increased and followed by the functional limb salvage procedure. But in one patient with osteosarcoma in the proximal tibia, the effect of pre-operative intra-arterial combination chemotherapy could not be increased, so amputation was required. He was changed to a post-operative intra-venous combination chemotherapy regimen selected by chemosensitivity test of the surgical material. All patients have been continuously disease-free at five to twelve months after surgery.

Adolescent↗

PubMed1994

Lymph node metastasis and macroscopic features in early gastric cancer.

The relationship between macroscopic features and the frequency and extent of lymph node metastasis was examined retrospectively in 421 patients with early gastric cancer. Nodal involvement was evident in 48 patients (11.4%): 7 out of 204 (3.4%) with mucosal cancer and 41 out of 217 (19.3%) with submucosal lesions. The incidence of metastasis to perigastric nodes and extraperigastric nodes was 2.9% and 0.5% for mucosal cancer, and 13.8% and 5.1% for submucosal cancer, respectively. There was no metastasis in lesions less than 1 cm in diameter, but the incidence of positive nodes increased with the size of the primary lesion. There was a low incidence of lymph node metastasis associated with lesions confined to the mucosa and less than 3 cm in size, elevated types of I and IIa less than 2 cm, and the flat type of IIb, while types consisting of a depressed portion such as IIc, III, IIc + III, and IIa + IIc often had not only perigastric but also extraperigastric nodal involvement, even when the lesion was small. As early gastric cancer can be cured by surgery, this modality is the treatment of choice. Endoscopic therapy in cases with a low involvement of lymph node metastasis can be considered when the patient is in a poor clinical state of health.

Adult↗

PubMed1994

[Basic and clinical evaluation of the effect of pirarubicin against head and neck cancer--chemosensitivity test and a comparative study with doxorubicin].

The chemosensitivities of 77 samples of human head and neck cancer were examined by in vitro succinate dehydrogenase inhibition (SDI) test. The tumor tissues obtained at biopsy specimens were exposed to doxorubicin (DXR) and pirarubicin (THP). The average decrease of the enzyme activity by THP was significantly greater than that by DXR. In 60 cases of squamous cell carcinomas, the chemosensitivity of poorly differentiated type tended to be higher compared to the well differentiated type. It is suggested from there results that THP is a more effective anticancer drug than DXR against human head and neck cancers. Clinically good responses were obtained in a systemic chemotherapy of such as head and neck adenoid cystic carcinomas by combining THP with other anticancer drugs such as CDDP (or CBDCA) and CPA.

Adult↗

PubMed1994

[Heterogeneity in gastric carcinoma with special reference to DNA content and mitotic activity: histopathologic differentiation].

DNA ploidy was microspectrophotometrically investigated in 46 patients with gastric carcinoma. Measurements of DNA content and mitotic index (MI) were examined in the mucosal, submucosal, muscularis propria, and serosal layers of tumors, respectively. The frequency of cells with values exceeding hexaploid chromosome (6c) and mitotic counting analysis revealed a significantly higher value in the serosa than in the mucosa. This tendency was not evident in differentiated type adenocarcinoma but was noted in those with the undifferentiated type. There were 37 tumors (80.0%) with the same DNA distribution pattern in every layer of the stomach (homogeneous DNA ploidy). Heterogeneity of DNA ploidy was observed in nine tumors (20.0%). Carcinoma with heterogeneous DNA ploidy manifested a significantly higher incidence of metastasis to lymph nodes than did those with the homogeneous type. Characteristically, there was venous permeation preponderance in the differentiated type and peritoneal dissemination preponderance in the undifferentiated type. This evidence of DNA heterogeneity in gastric carcinoma tissue suggests a possible correlation with metastatic behavior.

Adenocarcinoma↗