Biomedical subjects

M Fukumoto

Publications and source records attributed to M Fukumoto.

281 records · Page 16Linked to original sources

PubMedDate not supplied

Expression and cisplatin sensitivity of copper-transporting P-type adenosine triphosphatase (ATP7B) in human solid carcinoma cell lines.

One of the most important clinical problems in the treatment of human solid carcinoma is the intrinsic/acquired resistance. Cisplatin is a platinum compound that is one of the most effective agents in clinic. Copper-transporting P-type adenosine triphosphate (ATP7B) has been reported to be associated with cisplatin resistance by the experiment of transfection of full cDNA of ATP7B into KB3-1 lacking ATP7B. We examined the relationship between mRNA expression level of ATP7B and sensitivity to cisplatin in nine human ovarian carcinoma cell lines to extend these findings. mRNA expression level of ATP7B was significantly correlated with cisplatin-sensitivity in nine cell lines, raising the possibility that ATP7B could be a chemoresistance marker in some types of human solid carcinoma.

Adenosine Triphosphatases↗

PubMedDate not supplied

Expression of thymidine phosphorylase in human cervical cancer.

OBJECTIVE: Our aim was to evaluate whether the expression of thymidine phosphorylase (TP) by cervical cancer cells is correlated with the density of microvessels within the tumor, histopathologic features, and prognosis. METHODS: Sections of 55 cervical cancers (30 of stage IB, 5 stage IIA, and 20 stage IIB) were analyzed for the cellular expression of TP and the intratumoral density of microvessels by immunohistochemistry using monoclonal antibodies to TP and Factor VIII related antigen, respectively. The main outcome measures were the histopathologic features (histologic type, the maximum longitudinal diameter of the tumor, depth and degree of cervical stromal invasion, lymph-vascular space invasion, parametrial invasion, corpus invasion, vaginal invasion, and pelvic lymph node metastasis), whether or not the tumor cells were TP positive or TP negative, the microvessel count, and disease-free survival. RESULTS: Twenty-nine tumors (52.7%) were classified as TP-positive. The microvessel count (mean +/- SD, 45.6 +/- 12.8) in TP-positive tumors was significantly higher than that (mean +/- SD, 24.3 +/- 9.6) TP-negative tumors (P < 0.0001, Mann-Whitney U test). The disease-free survival of the patients with TP-positive tumors was significantly less than those with TP-negative tumors (P = 0.044, log-rank test). Multivariate analysis revealed that pelvic lymph node metastasis was to be the only independent prognostic factor for disease-free survival (P = 0.041). Moreover, disease-free survival in patients with TP-negative was longer than that in those with TP-positive in pelvic lymph node-negative subgroup, but this did not reach significance (P = 0.247, log-rank test). CONCLUSIONS: Although the expression of TP is not an independent prognostic factor in cervical cancer, it indicates a significantly decreased disease-free survival in patients with TP-positive tumors. These findings provide a potential for new therapeutic intervention mediated by nature that TP inherits in cervical cancer.

Adenocarcinoma↗

PubMedDate not supplied

Induction of apoptosis in glioma cells: an approach to control tumor growth by blocking basic fibroblast growth factor autocrine loop.

Glioma is a group of neoplasms derived from neuroepithelial tissue. High grade glioma is characterized by the presence of mitotic figures and the occurrence of vascular endothelial hyperplasia. This article reviews the effects of growth factors which are secreted by glioma cells on the proliferative activity of both glioma cells and vascular endothelial cells. Among various glioma-derived growth factors, we have found that basic fibroblast growth factor (bFGF) plays an important role in determining malignant trait of human glioma via its autocrine loop. Furthermore, we discuss candidate molecular targets for the therapy of high-grade glioma by blocking the autocrine loop of bFGF.

Animals↗

PubMedDate not supplied

Expression of E-cadherin and beta-catenin in primary and peritoneal metastatic ovarian carcinoma.

Protein expression levels of E-cadherin and beta-catenin were examined in 39 primary and 10 metastatic ovarian carcinoma to elucidate the role of these molecules in the extension of ovarian carcinoma by immunohistochemistry. Twenty-two of 39 (56%) ovarian carcinomas were preserved type and 17 of 39 (44%) were reduced type of E-cadherin. In contrast, 36 of 39 (92%) ovarian carcinomas were preserved type and 3 of 39 (8%) were reduced type of beta-catenin. E-cadherin expression in well-differentiated carcinoma was higher than that in moderately/poorly-differentiated carcinoma (p<0.05). Interestingly, 6 of 10 (60%) peritoneal metastatic lesions resulted in the reduced expression of E-cadherin compared with primary lesions. In contrast, only 2 of 10 (20%) metastatic lesions showed reduced expression of beta-catenin compared with primary lesions. Mutation of exon 3 of beta-catenin gene was rare (3%, 1/39) in carcinoma. These results suggested that the cell adhesion molecule E-cadherin might play an important role in the formation of peritoneal metastasis. In contrast, beta-catenin is not a good indicator of metastasis in human ovarian carcinoma.

Amino Acid Sequence↗

PubMedDate not supplied

Expression of thymidine phosphorylase and vascular endothelial growth factor in epithelial ovarian cancer: correlation with angiogenesis and progression of the tumor.

OBJECTIVE: The aim was first, to determine whether the expression of thymidine phosphorylase (TP) and vascular endothelial growth factor (VEGF) by epithelial ovarian cancer cells is correlated with the density of microvessels within the tumor and with ultrasonographic findings (B-mode classification and pulsed Doppler blood flow) and second, to speculate how these two angiogenesis factors participate in the tumorigenesis and tumor progression of epithelial ovarian cancer. METHODS: B-mode ultrasonography and color Doppler imaging and pulsed Doppler spectral analysis were used to scan patients with an overt ovarian mass immediately before laparotomy. Sections of malignant tumors were analyzed for the cellular expression of TP and VEGF and the intratumoral density of microvessels by immunohistochemistry using antibodies to TP, VEGF and Factor VIII related antigen, respectively. The main outcome measures were the histological classification of the tumor, the stage of the disease, whether or not the tumor cells were TP and VEGF positive or negative, the microvessel count and B-mode classification and the peak systolic velocity (PSV). RESULTS: Forty-four epithelial ovarian cancers were studied (6 of low malignant potential, 15 serous cystadenocarcinoma, 9 mucinous cystadenocarcinoma, 8 endometrioid adenocarcinoma, 4 clear cell carcinoma and 2 malignant Brenner tumor); 19 were Stage I, 6 Stage II, 15 Stage III and 4 Stage IV. Fourteen tumors (32%) were classified as TP positive and 21 (48%) as VEGF positive. The proportion of Stage I tumors that were TP positive (16%) was significantly lower (p = 0.022) than the corresponding value for Stages II-IV (44%), but the proportion with VEGF positive, the values for microvessel count and PSV were similar. Microvessel count did not significantly related to TP nor VEGF expression. The PSV was significantly higher in TP-positive tumors (p = 0.02) and VEGF-positive tumors (p = 0.006), respectively. There was a significant correlation between the microvessel count and the PSV (r = 0.34, p = 0.024). Moreover, specific B-mode classification significantly associated with disease stage and with TP expression, but not with VEGF expression. CONCLUSIONS: Angiogenesis is an early, critical step in the tumorigenesis of epithelial ovarian cancer, however, it does not provide significant information about tumor aggressiveness. When TP expression is superimposed upon the VEGF expression, the tumor might acquire the aggressive tumor phenotype.

Adenocarcinoma, Clear Cell↗

PubMedDate not supplied

Antitumor activity of 5'-deoxy-5-fluorouridine in human digestive organ cancer xenografts and pyrimidine nucleoside phosphorylase activity in normal and neoplastic tissues from human digestive organs.

5'-Deoxy-5-fluorouridine (5'-DFUR) is believed to be metabolized to 5-fluorouracil (5-FU) by pyrimidine nucleoside phosphorylase (PyNPase). PyNPase activity is reported to be higher in neoplastic tissues than in normal tissues, and this has been proposed as an explanation for the selective cytotoxicity of 5'-DFUR against tumors. In the present study, PyNPase activity was measured in 95 neoplastic and normal specimens from human digestive organ tissues. In specimens from the esophagus, stomach, intestine and pancreas, PyNPase activity was higher in neoplastic tissues than in normal tissues. However, PyNPase activity in non-malignant liver tissues, especially cirrhotic liver tissues, was much higher than in the normal tissues of the other digestive organs. PyNPase activity in non-malignant liver tissues was a high as in primary liver tumors, and PyNPase activity in metastatic liver tumors was lower than in primary tumors and non-malignant cirrhotic tissues. The in vivo antitumor activities of oral 5'-DFUR and intravenous 5-FU were also assessed in 6 human digestive organ cancer xenograft lines transplanted subcutaneously in nude mice, and the relationship between the in vivo antitumor effects of 5'-DFUR and PyNPase activity in the tumors was assessed. However, there was no statistically significant correlation between them. Although the in vivo antitumor effect of intravenous 5-FU correlated significantly with the in vitro sensitivity of the tumors to 5-FU (assessed by DNA synthesis inhibition assay), the in vivo effects of 5'-DFUR did not correlate with the in vitro sensitivity to 5-FU. It is suggested that: (a) the liver may be the major site for metabolizing 5'-DFUR to 5-FU, and (b) measuring PyNPase activity in the tumor may not be a useful indicator for chemotherapy with 5'-DFUR.

Adenocarcinoma↗

PubMedDate not supplied

The role of additional chemotherapy with oral UFT in intravenous combination chemotherapy with cisplatin and 5-fluorouracil for human gastric cancer xenograft lines of well- and poorly- differentiated adenocarcinomas transplanted in nude mice.

In order to assess the role of maintenance chemotherapy with the oral anticancer agent UFT, a mixture of uracil and futraful, in the intensive intravenous chemotherapy for gastric cancer, nude mice transplanted with human gastric cancer xenografts were treated with intravenous 5-fluorouracil (5-FU) and cisplatin (CDDP), alone or in combination, with or without the oral anticancer agent UFT. UFT was given at its maximal clinical dose of 10 mg/kg of body weight daily for 2 weeks, while 5-FU and/or CDDP was intravenously administered at the dose of 20 mg/kg and 1.8 mg/kg of body weight respectively once a week, alone or in combination, for two weeks. The results revealed that 5-FU or CDDP alone were ineffective for both GC-YN, a well differentiated adenocarcinoma line, and GC-SF, a poorly differentiated adenocarcinoma line; however, UFT was effective for GC-SF. In combinations, only the three-agent combination 5-FU + CDDP + UFT (FPU) was effective for GC-YN; however, all the two-agent combinations and FPU were effective for GC-SF. FPU significantly suppressed the growth of GC-YN much more than all the other treatment groups. In contrast, although all combinations as well as UFT alone were effective for GC-SF, there was no significant difference among these effective groups. Moreover, no side effects were noted in combined use of UFT. This study suggests that oral UFT as a maintenance treatment may be beneficial in the combination chemotherapy for human gastric cancer.

Adenocarcinoma↗

PubMedDate not supplied

Relationships for recombinant interleukin-2-stimulated mixed lymphocyte tumor extract reaction between peripheral blood lymphocytes and regional node lymphocytes in gastric cancer patients.

To investigate the relationship between "systemic" antitumor immunity and "local" antitumor immunity with respect to the histopathological stage of gastric cancer, interleukin-2 stimulated mixed lymphocyte tumor extract reactions (ILS-MLTR) of peripheral blood lymphocytes (PBL) and regional node lymphocytes (RNL) were evaluated in 59 gastric cancer patients. ILS-MLTRs of both PBL and RNL decreased with the advance of cancer stage, but ILS-MLTRs of PBL were always lower than those of RNL. Positive correlations in MLTR between PBL and RNL were found in patients with depth of invasion to muscularis propria and serosa and peritoneal dissemination. Inverse correlations between PBL and RNL were noted in patients with stage IV and distant nodal involvement. These results suggest that variations in the anticancer immunities might be effectively managed by an immunotherapy which is designed according to the responsiveness in the immune parameter ILS-MLTR.

Cells, Cultured↗

PubMedDate not supplied

Cathepsin activity in cholesteatoma.

Collagenolytic cathepsin, presumed to play an important role in bone destruction of cholesteatoma, was investigated in cholesteatoma epithelium, subepithelial granulation tissue, skin from the bony external auditory meatus and, temporal bone. The enzyme extracted from tissues was proven to be lysosomal cathepsin B by SDS gel electrophoresis in the use of human type I and type III collagen. alpha-N-benzoyl-DL-arginine-2-naphthylamide HCl (BANA) was supposed to be specific for cathepsin B, and so BANA-hydrolase activity was measured as collagen-degrading cathepsin. The results showed that tissues had cathepsin B with its optimal pH 6.0, and that cathepsin B activity revealed a significant increase in the subepithelial granulation tissue. A strong activity of acid phosphatase found in the subepithelial granulation tissue seems to reflect the existence of an active metabolism of substances in the granulation tissue. These findings suggest that collagen is resorbed in the subepithelial granulation tissue in the presence of cholesteatoma.

Acid Phosphatase↗

PubMedDate not supplied

Neoadjuvant chemotherapy of gastric cancer with oral UFT (a mixture of uracil and fturafur) during the waiting period for surgery.

Our previous experience has demonstrated that growth of gastric cancer during the waiting period for surgery cannot be neglected, and some patients hope to receive prophylactic treatment to inhibit the growth of tumor until surgery. The present study was designed to assess the clinical benefits of preoperative chemotherapy with oral UFT for gastric cancer during the waiting period for surgery. Fifty patients with gastric cancer (24 early, 25 advanced and 1 recurrent cancers) were treated with oral UFT at 300-600 mg/day for 7-36 days before surgery and the objective responses and the postsurgical survivals were evaluated. In 42 of 50 patients objective responses of primary lesions were assessed by endoscopy or upper gastrointestinal series examination, and 2 CRs, 15 PRs and 25 NCs were seen (40% response). The histological effect was evaluated in 50 patients and the following classifications were made: grade 3 (complete disappearance or necrosis of tumor cells), 2; grade 2 (necrotic changes > 2/3 area), 4; grade 1b (> 1/3 area), 7; grade 1a (< 1/3 area), 15; and grade 0 (no histological changes), 22. A longer period of UFT administration was associated with CR or PR. All the patients underwent gastrectomy (38 curative and 12 palliative gastrectomies): all patients with Stage I-III primary gastric cancer are alive after surgery, and the 50% survival period of the patients with Stage IV cancer was 20 months. The side effects were not serious, including slight myelotoxicity, liver dysfunction and anorexia. It is concluded that preoperative chemotherapy for gastric cancer with oral UFT on outpatient basis may result in down-staging as well as the prevention of tumor growth during the waiting period for surgery without serious side effects.

Administration, Oral↗

PubMedDate not supplied

Anticancer chemosensitivity and growth rate of freshly separated human colorectal cancer cells assessed by in vitro DNA synthesis inhibition assay.

The present study was designed to assess the chemosensitivity profile of freshly separated colorectal cancer cells and to screen effective agents for the design of new combination regimens. The DNA synthesis and chemosensitivity (% inhibition of DNA synthesis by the anticancer agent) were successfully assessed in 184 samples (107 primary and 77 metastatic or recurrent lesions) from 152 patients with colorectal cancer using an 3H-thymidine incorporation assay, and the correlations between these two measures and various clinicopathological factors were analysed. DNA synthesis was highest in nodal metastasis followed by malignant effusion, primary lesion, liver metastasis, and local recurrence. DNA synthesis liver metastasis and local recurrence were significantly lower than in other lesions. The results of the chemosensitivity assay are as follows: 5-FU seems to be the most beneficial for primary colorectal cancer; carboquone (CQ), etoposide (VP-16), 5-FU, and mitomycin-C (MMC) for nodal metastasis; CQ, cisplatin (CDDP), 5-FU, adriamycin (ADR) and VP-16 for malignant effusion; and VP-16, CDDP and CQ for liver metastasis. However, the present results showing the chemosensitivity profiles in different lesions suggest that regimens including 5-FU with VP-16 and CQ in addition to MMC or ADR may be applicable for all kinds of colorectal cancer lesions. These results demonstrated the heterogeneity in the chemosensitivity of colorectal cancer, which suggests not only the necessity of patient-specific chemotherapy dependent on the sensitivity assay, but also the usefulness of the present results in the choice of agents for widely applicable combination regimens for colorectal cancer.

Antineoplastic Agents↗