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Biomedical subjects

T Kamata

Publications and source records attributed to T Kamata.

At least 145 records · Page 8Linked to original sources

[Expression of proliferation associated nuclear antigen P-105 in human gastric cancers: as a new marker for metastasis].

Expression of proliferation associated nuclear antigen P-105 was examined with flow cytometry in forty-three patients with advanced gastric cancer. Expression of P-105 was observed abundantly in cancer, about four times than normal mucosa, but little in normal gastric mucosa. We evaluated the expression of P-105 in cancer as P-105 intensity: mean FITC levels of G0G1 of the cancer cells/those of normal cells. The P-105 intensity did not correlate with DNA index or S-phase fraction. Furthermore, it did not correlate with histologic type, stromal type, infiltrating type, and gross appearance. However, P-105 intensity was significantly higher in the patients with hepatic metastasis, and lower in those with peritoneal dissemination than those without metastasis, respectively. From the results, it was supposed that P-105 intensity might be a useful indicator for metastatic type different from those previously reported in human gastric cancers.

Antigens, Neoplasm↗

Tissue status of epidermal growth factor and its receptor as an indicator of poor prognosis in patients with gastric cancer.

An immunohistological study of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) was made with 157 specimens of stomach cancer. EGF stained positively in 70 specimens (45%), and EGFR in 53 specimens (34%). The cancers were classified into three groups; Group 1 with neither EGF nor EGFR staining positively (67 tumors); Group 2 with either EGF or EGFR staining positively (57 tumors); and Group 3 with both EGF and EGFR staining positively (33 tumors). The incidence rates of tumors of macroscopically infiltrative, poorly differentiated, deep invading and node-positive types were significantly higher for Group 3 than for Groups 1 and 2. The bromodeoxyuridine labeling indices (BrdU LIs) were significantly higher for Group 3 (median: 15.1%) than for Group 1 (median: 10.7%) or Group 2 (median: 11.4%). Patients with synchronous expression of EGF and EGFR (Group 3) had the poorest prognosis. From the results, it may be concluded that tumors with synchronous expression of EGF and EGFR have the highest malignant potentials and this phenomenon may cause autocrine secretion for self-replication.

Adult↗

[Treatment of gastric cancer patients with peritoneal metastasis by continuous hyperthermic peritoneal infusion with mitomycin C and cisplatin].

Following the resection of its primary lesion, continuous hyperthermic peritoneal perfusion (CHPP) with anticancer drug (mitomycin C, cisplatin) containing warmed physiological saline was performed on gastric cancer having peritoneal dissemination, and the effect of CHPP was examined by second look operation (SLO). The subjects were 41 cases of gastric cancer with peritoneal dissemination but without hepatic metastasis, which we have experienced in the past 7 years. The prognosis of these CHPP-treated cases was such that 50% survival period, 3 year survival rate and 5 year survival rate were 398 days, 28.5 and 12%, respectively. Comparison of the effects of CHPP by SLO revealed remarkable diminution of the peritoneal dissemination in 7 (44%) of 16 cases and disappearance of the ascites with a single course of CHPP in 7 of ascitic cases. Long-term survival (greater than 3 years) was noted in 4 of the CHPP-treated cases. Side effects were renal insufficiency, leukopenia and small intestinal perforation in 2(5), 2(5) and 1 cases (2%), respectively. The above results suggested the effectiveness of CHPP for the treatment of gastric cancer having peritoneal dissemination.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical experiences with hyperthermochemotherapy of hepatic metastasis from gastric cancer].

Thermochemotherapy was performed on gastric cancer cases of hepato-metastasis. The subjects were 12 gastric cancer cases having hepato-metastatic lesions (10 synchronous, 2 heterochronous). Using 8 or 13.58 MHz-dielectric heating apparatus, thermotherapy was carried out for 40-60 min (twice a week, 5-35 times, averaging 12.8 per case) at an intra-tumoral temperature greater than 42 degrees C. Chemotherapy consisted of hepato-arterial infusion of MMC 10 mg/BW, CDDP 75 mg/m2 once per 3-4 weeks and consecutive daily administration p.o. of UFT 800 mg/BW. Effect greater than PR was noted in 75% (9/12) on the whole and in 100% (5/5) and 57% (4/7) for H1-2 and H3, respectively. Mean and 50% survival periods were 9.3 and 7.2 months, respectively, with a one-year survival rate of 38%. Chemotherapy-induced side effects were nausea and vomiting in 83% and leukopenia and thrombopenia in 67%, while the only thermotherapy-induced side effect was subcutaneous fatty tissue necrosis in 3 cases. The above results suggested the effectiveness of the present thermochemotherapy in the treatment of hepato-metastasis of gastric cancer.

Administration, Oral↗

Relation of proliferative activity to survival in patients with advanced gastric cancer.

The proliferative activities of 98 biopsied specimens of advanced gastric cancers were measured by the in vitro bromodeoxyuridine (BrdU) labelling method. BrdU labelling indices (LIs) varied from 4.8 to 45.1%. There was no correlation of BrdU LIs and histological type, distant metastasis, serosal invasion, macroscopic type or tumor size. However, BrdU LIs of tumors with lymph node metastases were significantly higher than those without them. Patients with tumors showing high BrdU LIs had a three-fold relative risk of death, as compared with those showing low BrdU LIs. When the BRdU LIs and all the clinicopathological parameters were entered simultaneously into the Cox model, BrdU LIs, peritoneal dissemination and serosal invasion emerged as independent prognostic parameters. These results indicate that the in vitro BrdU labelling method using biopsied materials may be useful in predicting lymph node metastasis preoperatively and designing operative procedures for individual patients.

Bromodeoxyuridine↗

[The surgical results of pancreatoduodenectomy and total pancreatogastrectomy combined with autotransplantation of the distal half of the pancreas for the treatment of advanced gastric cancer located in the lower half of the stomach].

In the last 16 years we employed pancreaticodudenectomy (PD) on 27 patients with cancers of the distal third of the stomach, associated with duodenal invasion, invasion to pancreatic head, or n3 metastasis. More recently, total gastrectomy and total pancreatectomy combined with heterotopic autotransplantation of the distal pancreas (TGTP) was performed in 7 patients with n4 metastases. These cases were compared with 56 patients who underwent subtotal gastrectomy (SG) in the same period. When the survival rates were compared, PD provided better long-term results than SG, especially on the patients with tumors infiltrating into the pancreas head. On the contrary, there was no significant survival advantage in patients with duodenal invasion or n3 metastasis between PD group and SG group. TGPT showed the longest survival for the patients with n4 metastasis. These results indicate that PD is a rational and safe method for the treatment of gastric cancer infiltrating into the pancreas head. In addition, TGTP may be the most radical procedure for the treatment of gastric cancer with n4 metastases.

Duodenum↗

A clinicopathologic study on multiple gastric cancers with special reference to distal gastrectomy.

Simultaneous multiple gastric cancer was seen in 49 (5.8%) of 852 resected stomachs. Patients with multiple cancers were older than those with single gastric cancers (P less than 0.01) and the incidence of multiple gastric cancer was significantly higher in male patients than in female patients (P less than 0.05). The incidence rates of multiple carcinomas were 9.6% of early gastric carcinomas and 4.0% of advanced gastric carcinomas. With regard to histologic type, the incidence rate of the differentiated type was 71% and the incidence rate of the undifferentiated type was 29%. In 68 serially resected stomachs, 5 (7.4%) new multiple cancers were detected microscopically, whereas 4 (5.9%) had already been diagnosed grossly. The incidence rate of multiple carcinoma increased to 13.2% by this procedure. The cases that were cut serially showed that most of the multiple cancers were located distally from the F-line presenting the line along which intestinal metaplasia appeared. This study suggests that the surgeon is required to resect the area including the F-line at the time of distal gastrectomy so as not to leave another cancer in the gastric remnant.

Adult↗

Growth fractions in gastric carcinomas determined with monoclonal antibody Ki-67.

The growth fractions of 101 gastric carcinomas were determined in situ by immunostaining with the monoclonal antibody Ki-67 and the results correlated with the histopathologic findings, bromodeoxyuridine (BrdU) labeling index, and DNA ploidy pattern. DNA ploidy patterns were determined by flow cytometric analysis. The Ki-67 labeling rates are rated from 4.6% to 82% (mean, 22%). A significant correlation was found between Ki-67 labeling rates and BrdU labeling indices. Sixty-seven percent of tumors with lymph node metastases showed Ki-67 labeling rates of less than 22%, whereas 33% of tumors without lymph node metastases showed Ki-67 labeling rates of less than 22%. There was a significant correlation between these two groups. Tumors with vessel invasion more often have higher Ki-67 labeling rates than those without vessel invasion. By the DNA ploidy classification, the mean Ki-67 labeling rates of aneuploid tumors was significantly higher than that of diploid tumors. This method yielded similar results to those obtained by BrdU labeling and flow cytometric study. The measurement of Ki-67 labeling rates may be useful to decide the therapeutic modalities.

Antibodies, Monoclonal↗

Retrospective analysis of the prognostic significance of DNA ploidy patterns and S-phase fraction in gastric carcinoma.

Paraffin-embedded tumor samples from 493 gastric carcinoma patients were analyzed by DNA flow cytometry. The results were correlated with clinicopathological findings and S-phase fractions measured by in vivo bromodeoxyuridine (BrdUrd) labeling. Of the 493 patients, 183 (37%), 225 (46%), and 85 (17%) showed diploidy, single DNA-aneuploidy, and DNA-multiploidy patterns, respectively. When the DNA histogram and all the clinicopathological parameters were entered simultaneously into the Cox regression model, DNA ploidy, liver metastasis, peritoneal dissemination, and nodal status emerged as independent prognostic parameters. The relative risk of death was twofold higher in single DNA-aneuploid and threefold higher in DNA-multiploid tumors than in DNA-diploid tumors. BrdUrd labeling indices (LIs) also proved to be an independent prognostic factor. Multiploid tumors showed the highest median BrdUrd LI associated with the most frequent peritoneal dissemination and liver metastasis. The simultaneous evaluation of DNA ploidy patterns and BrdUrd LIs gave more prognostic information than the determination of tumor DNA ploidy only. Namely, DNA diploid, together with low BrdUrd LIs, was associated with favorable prognosis, whereas DNA aneuploid with high BrdUrd LIs was related to the poorest prognosis. These results indicate that DNA ploidy and BrdUrd labeling indices may be possibly useful prognostic factors for gastric carcinoma.

Aneuploidy↗

Continuous hyperthermic peritoneal perfusion for the treatment of peritoneal dissemination in gastric cancers and subsequent second-look operation.

A total of 31 patients with gastric cancer showing peritoneal dissemination received continuous hyperthermic peritoneal perfusion (CHPP) in combination with the administration of cisplatin (CDDP) and mitomycin C (MMC). The authors developed a new special device named the peritoneal cavity expander (PCE) for sufficient perfusion and direct temperature measurement in the peritoneal cavity. As complications of CHPP three patients presented with bone marrow suppressions (leukocytes less than or equal to 3000/mm3 and/or platelets less than or equal to 30,000/mm3): one, leakage of intestinal anastomosis; one, intestinal perforation; and one, acute renal failure. But none of them was lethal. Twelve of 31 patients who had received CHPP during the initial operation underwent second-look operation (SLO) for the assessing the effects of CHPP and for resecting residual or recurrent tumors. Among 12 patients who received SLO complete response (CR) was observed in four patients, partial response (PR) in one, no change (NC) in three, and progressive disease (PD) in four, with the overall response rates (%CR + %PR) standing at 41%. Two-year survival rate of the complete and partial responders was 50%, which was significantly higher than 0% of the other responders (NC + PD). The survival curves of the two groups were significantly different (P less than 0.05, generalized Wilcoxon test). These results supported that CHPP was well tolerated and effective for the treatment of patients with peritoneal dissemination in gastric cancer when combined with anti-cancer drugs having synergism with hyperthermia. Since the outcome of SLO was one of prognostic factors it was important to follow up these patients by SLO.

Adult↗

A novel membrane factor stimulates guanine nucleotide exchange reaction of ras proteins.

A factor with a molecular weight of 100 kDa, which markedly enhanced the guanine nucleotide exchange reaction of ras p21 proteins, was partially purified from bovine brain tissues. The factor was predominantly associated with the plasma membrane. When the partially purified factor and excess cold GTP were added to [3H]GDP.Gly12 p21 or Val12 in the presence of 2 mM MgCl2, the nucleotide exchange rate was stimulated up to 25-fold. The stimulation of the p21-nucleotide exchange reaction by the factor was completely blocked by the Y13-259 ras-neutralizing antibody. Taken together, these results suggest that the factor may control the rate limiting GDP/GTP exchange step in recycling of p21 in ras-mediated signal transduction.

Animals↗

Relation of proliferative activity to survival in patients with gastric carcinoma.

The prognostic significance of proliferative activity in 167 gastric carcinomas was studied by means of an in vitro labeling method with bromodeoxyuridine (BrdU), using specimens obtained by endoscopic biopsy, and the results were correlated with conventional prognostic factors. The BrdU labeling indicates (BrdU LI) varied from 2.1 to 45%. When the in vitro BrdU LI were plotted against in vivo BrdU LI, a significant correlation was found between in vitro and in vivo BrdU LI (P less than .01). These results show that the in vitro BrdU LI of specimens obtained by endoscopic biopsy indicate accurate proliferative activities of gastric cancers. The BrdU LI were closely correlated with nodal status, vessel invasion, and tumor size. With regard to the correlation of BrdU LI and prognosis, patients whose tumors had a high BrdU LI (BrdU greater than LI less than 10%). When the BrdU LI and all the pathologic findings were entered simultaneously into the regression model, nodal status, tumor size, serosal involvement, and BrdU LI emerged as independent prognostic parameters. The present studies demonstrated the usefulness of the in vitro BrdU-labeling method to estimate the malignancy of gastric cancer preoperatively, and this method may be useful in designing the operative procedure and multimodal therapy for individual patients.

Antibodies, Monoclonal↗

Purification of a factor capable of stimulating the guanine nucleotide exchange reaction of ras proteins and its effect on ras-related small molecular mass G proteins.

We have previously identified a membrane factor capable of stimulating guanine nucleotide exchange activity for ras p21 proteins. The ras guanine nucleotide exchange factor (rGEF) was purified from bovine brain to near homogeneity by successive chromatographies on DE52 DEAE-cellulose, Sepharose 6B, hydroxylapatite, and FPLC phenyl-Superose resins. SDS/polyacrylamide gel electrophoresis of the purified rGEF showed a single major protein with a molecular mass of 35 kDa. rGEF increased the exchange rate of GDP in normal [Gly12]p21 or oncogenic [Val12]p21 up to 30- to 40-fold under physiological concentrations of Mg2+. Since the factor was free from GDP/GTP binding activity and nonspecific GDP hydrolytic activity, we propose that rGEF may regulate GDP/GTP exchange reaction of ras proteins in response to external growth signals. Moreover, rGEF enhanced the dissociation of bound GDP from some of ras-like G proteins, R-ras, rap1-A, rab1-B, and rho proteins, raising the possibility that rGEF may affect the activities of these proteins.

Animals↗

Modulation of maturation and ribosomal protein S6 phosphorylation in Xenopus oocytes by microinjection of oncogenic ras protein and protein kinase C.

Using Xenopus oocytes as a model system, we investigated the possible involvement of ras proteins in the pathway leading to phosphorylation of ribosomal protein S6. Our results indicate that microinjection of oncogenic T24 H-ras protein (which contains valine at position 12) markedly stimulated S6 phosphorylation on serine residues in oocytes, whereas normal ras protein (which contains glycine at position 12) was without effect. The S6 phosphorylation activity in the cell extract from T24 ras protein-injected oocytes was increased significantly. In addition, injection of protein kinase C potentiated the induction of maturation and S6 phosphorylation by the oncogenic ras protein. A similar potentiation was detected when T24 ras protein-injected oocytes were incubated with active phorbol ester. These findings suggest that ras proteins activate the pathway linked to S6 phosphorylation and that protein kinase C has a synergistic effect on the ras-mediated pathway.

Animals↗