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Biomedical subjects

T Kamata

Publications and source records attributed to T Kamata.

At least 199 records · Page 11Linked to original sources

Effects of ras-encoded proteins and platelet-derived growth factor on inositol phospholipid turnover in NRK cells.

The role of ras-encoded proteins and platelet-derived growth factor (PDGF) in inositol phospholipid metabolism has been studied. PDGF stimulates inositol phospholipid turnover in confluent normal rat kidney (NRK) cells and enhances hydrolysis of phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate in NRK cell membranes in the presence of guanosine 5'-[gamma-thio]triphosphate. The stimulatory effect of PDGF on phosphatidylinositol bisphosphate hydrolysis is not inhibited by pretreatment of NRK cells with pertussis toxin, implying that PDGF-stimulated phospholipase C activity of NRK cells is regulated by a pertussis toxin-insensitive guanine nucleotide-binding protein (G protein) that is different from Gi (inhibitory G protein) or Go (G protein of unknown function). When bacterially made human normal or oncogenic T24 ras protein is added to 32P-labeled NRK cell membranes in the presence of guanosine 5'-[gamma-thio]triphosphate, normal ras protein increases by 3-fold the formation of inositol trisphosphate, whereas T24 ras protein has no significant effect. In addition, normal ras protein and PDGF have additive effects on inositol trisphosphate production. Taken together, these data suggest that normal ras protein stimulates inositol phospholipid turnover in NRK cells by means of a pathway different from the PDGF-regulated one and that oncogenic ras protein is without significant stimulatory effect in this action.

Animals↗

[Correlation of epidermal growth factor receptor status and clinical outcome in gastric carcinoma].

Analysis of epidermal growth factor receptor (EGFR) was performed on 242 primary gastric carcinomas and the results correlated with histologic findings and S-phase fractions measured by bromodeoxyuridine (BrdU) labeling. They were stained for EGFR by means of an indirect immunoperoxidase technique using a monoclonal antibody against the receptor. Seventy-six of these cancer tissues exhibited EGFR reactivities. All the cancer cell membranes were stained and sometimes the stroma were stained. These EGFR status were then compared on the basis of pathologic findings including macroscopic type, depth of invasion, differentiation type, vascular invasion and lymph node metastasis. Staining for EGFR in Borrmann's 3 or 4 type was significantly stronger than those in other macroscopic types. The staining for EGFR was closely related to the poorly differentiated type and frequent serosal involvement. BrdU labeling index was studied in 25 cases. These values were from 2.3% to 18.6%, with a mean of 10.4%. The mean BrdU labeling index of EGFR positive cases was 12.2%, of negative cases 7.6%, respectively. There was a good correlation between BrdU labeling index and EGFR status. In addition, There was a signifiCANT 8P less than 0.05) correlation between the presence of the EGFR and poor prognosis. However, EGFR status was not significantly correlated with the lymph node metastasis, vessel invasion and size of the tumors. These results indicate that demonstration of EGFR status may be useful in prognosis and this receptor may be a suitable target for therapy.

Adenocarcinoma, Scirrhous↗

[Malignancy in gastric carcinoma, with special reference to the DNA ploidy and proliferative activity].

Analysis of DNA ploidy patterns was performed on 129 primary gastric cancers and the results correlated with histologic findings and in vivo bromodeoxyuridine (BrdU) labeling. Forty-nine cases were diploid (38%) and 80 cases were aneuploid. There was no correlation between DNA ploidy and histologic type. In aneuploid cancers, incidence of lymphatic invasion, lymph node metastasis and rate of advanced cases were significantly higher than those in diploid tumors. During the follow-up period of 5-10 years, 23 of the 40 patients (55%) with aneuploid tumors died of disease within 3-120 months. Only 13 of the 36 patients (36%) with diploid tumors died of disease. The BrdU labeling indices (BrdU LI) were from 2.8% to 26.7%, with a mean of 10.4%. There was no correlation between BrdU LI and histologic type or stage. The mean BrdU LI of early cancers was 8.1%, of advanced cancers, 11.9%. BrdU LI of cancers with lymphatic invasion or lymph node metastasis was higher than those without them. The mean BrdU LI of diploid cancer was 6.0%, of aneuploid cancers, 11.9%. There was a good correlation between BrdU labeling indices and DNA ploidy patterns. These results indicate that determination of DNA ploidy patterns and growth fractions by BrdU labeling may be useful in the conjecture of prognosis of the patient and in the selection of patients from various modalities.

Aneuploidy↗

[Human epidermal growth factor (h-EGF) in gastric carcinomas].

Two hundred and twenty one gastric carcinomas were immunohistochemically stained for h-EGF and we examined the correlation between h-EGF immunoreactivities and histologic findings. Regarding macroscopic and histologic types, incidence of h-EGF immunoreactivities in infiltrating type and in poorly differentiated type was significantly higher than those in localized type and in differentiated type, respectively. In addition, h-EGF producing carcinomas showed high positive rate in prognostic serosal involvement and scirrhous type in stroma. Prognosis in patients with h-EGF producing tumors was poorer than that in those with h-EGF non-producing tumors, especially in stages II and III. These results suggest that h-EGF immunoreactivities serves as a biological marker of high malignancy.

Adenocarcinoma↗

Insulin stimulates the phosphorylation level of v-Ha-ras protein in membrane fraction.

Insulin was found to stimulate the phosphorylation of the 21,000-dalton protein encoded by the ras oncogene of Harvey murine sarcoma virus in membrane fraction both in vivo and in vitro. When the human ras proteins expressed in E. coli were reconstituted with purified human insulin receptor, GTPase activity of normal or its mutated oncogenic ras protein was not stimulated by the addition of insulin. Likewise, tyrosine kinase activity or insulin binding capacity of the receptor was not influenced when assayed in the presence of the ras proteins. These results suggest that ras proteins may be coupled with the insulin receptor system through some unidentified membrane factors.

Animals↗

Exact mechanisms contributing to instability and refractoriness to therapy in patients with unstable angina: coronary arteriographic evaluation.

Ninety one patients with unstable angina were evaluated by clinical and angiographic study. Of 91 patients, 42 (46%) responded poorly to the intensive medical treatment. Emergency coronary arteriography was then performed on these patients. The important pathoanatomical mechanisms contributing to instability of angina pectoris and/or refractoriness to the intensive medical treatment were observed in 19 of 42 patients (45%). These include: 1) More severe disease with left main lesion; 2) Refractory coronary spasm; 3) Coronary dissection; 4) Rapid progression of atherosclerosis; 5) Ulcerating plaque and 6) Coronary thrombus. Our results presented here suggest that an appropriate knowledge regarding pathophysiology might improve the approach to treatment.

Adult↗

Reduced protein kinase C activity in a ras-resistant cell line derived from Ki-MSV transformed cells.

We have examined phosphatidylinositol turnover and C-kinase distribution in a flat cellular ras-resistant cell line (C11) derived from Kirsten murine sarcoma virus (Ki-MSV) transformed NIH/3T3 cells (DT). This cell type has been shown to express high levels of the p21 Ki-ras gene product yet is resistant to the transforming effects of this protein. Our data indicate that C11 cells have reduced levels of total C-kinase activity when compared to NIH/3T3 cells and do not retain the ability to phosphorylate the growth associated 80-kDa C-kinase substrate either in vivo or in vitro. Furthermore, whilst the steady state levels of diacylglycerol and the sum of inositol phosphates are elevated in DT cells, in C11 cells these levels are reduced to an amount equivalent to that seen in NIH/3T3 cells. These data indicate a correlation between a protein kinase C dependent pathway and resistance to transformation by ras.

Cell Compartmentation↗

[Evaluation of immunochemotherapy in patients with primary liver cancer. Osaka Research Society for Liver, Gallbladder and Pancreas].

The effectiveness of BRM (biological response modifier) for primary liver cancer was investigated in a prospective randomized and well controlled study. The protocol consisted of 3 groups: 1) Tegafur oral administration only, 2) OK-432 i.v. plus Tegafur, and 3) PSK oral application plus Tegafur. One hundred seventy-two Japanese patients were entered. The results revealed that BRM addition was more effective than Tegafur therapy alone with regard to tumor regression and the results of clinical examinations, but that there was no difference in subjective symptoms between the use of BRM and the other regimes. As to prognosis, patients given PSK survived longer than those given Tegafur alone, but OK-432 group had the same survival rate as the other two groups as a whole. The relationship among the three groups with regard to survival time, was similar to that of their respective total efficacies. Between the three groups, there was a significant difference in the incidence of adverse effects. The difference was sustained with the occurrence of fever symptoms as a result of OK-432 stimulation, with and BRM therapy decreased the gastro-intestinal side effects in comparison with the control group.

Adult↗

[A case of parotid tumor showing remarkable regression following hyperthermo-chemo-radiotherapy].

A 72-year-old woman developed adenocarcinoma of the left parotid gland. Because of the excessive size of her tumor and the fact that she suffered from severe liver dysfunction, she was treated by hyperthermo-chemo-radiotherapy (HCR therapy). After ten sessions of radiofrequency hyperthermia with HEH 500 (13.56 MHz radiofrequency wave), 50-Gy irradiation from a linac and administration of 33.0g of tegafur in suppository form, the tumor mass showed remarkable regression decreasing in size by as much as 84% on computed tomography. Histologically the tumor which was resected under local anesthesia, showed almost total necrosis. The multidisciplinary HCR therapy was well tolerated and effective as a therapy for cancer in this case.

Adenocarcinoma↗

[Multimodal therapy using hyperthermia for gastric cancer--with special reference to histological studies].

We carried out a combination preoperative therapy involving radiofrequency hyperthermia (8 MHz or 13.56 MHz) with radiation (10-MV X-ray) or chemotherapy (Mitomycin C, CDDP or UFT) for 24 advanced gastric cancers with the aim of preventing local recurrence and improving resectability. The tumor and histological effects were evaluated in each case. Furthermore, an agar phantom possessing a cavity, for simulating the stomach, was employed in an experiment to evaluate temperature distribution upon RF-heating. In the experiment using the agar phantom, the rising temperature around the cavity at 3 o'clock was higher than at 5' and 6 o'clock. This suggested that gastric juice and air must be aspirated when treating a patient by RF-heating. Of the 24 tumors, 4 (17%) showed partial response. Histological effects were observed in 67% of 21 primary tumors. The rate of histological effects in metastases of lymph nodes, liver and peritoneum were 29% (4/14), 100% (2/2) and 0% (0/4), respectively. Tumor response was closely correlated with irradiation and the temperature in the stomach cavity (over 42.5 degrees C). Almost all patients showed good tolerance of this combined therapy. These results show that combined treatment involving radiation, chemotherapy and hyperthermia appears to be a potentially useful from of preoperative therapy for patients with advanced gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinicopathological studies of nuclear DNA distribution in colorectal cancer].

The nuclear DNA content of paraffin-embedded materials was measured by microfluorometry in 108 colorectal (59 colon and 49 rectal) cancers and 29 metastatic liver tumors from the colorectum. The classification of the nuclear DNA distribution is as follows: Low ploidy, 10% greater than over 4C; intermediate ploidy, 10% less than or equal to over 4C and 10% greater than over 6C; high ploidy, 10% less than or equal to over 6C. In primary lesions, thirty-one (29%) were found to contain cells with high ploidy. The ploidy pattern was not related to pathological stage. However, in curatively resected cases, only 24% of patients with high ploidy survived 10 years. This 10 year-survival rate was significantly lower as compared with 80% and 88% of patients with intermediate and low ploidy, respectively (p less than 0.05). In non-curatively resected cases, no patients with high ploidy survived 2 years, although 21% and 67% of patients with intermediate and low ploidy survived, respectively. In metastatic liver lesions, eleven materials (42%) were found to contain cells with high ploidy. Prognosis of patients with high ploidy was worse than that with intermediate and low ploidy (p less than 0.05). These observations suggest that the nuclear DNA distribution in colorectal cancers may be an important prognostic factor, independent of pathological stage.

Colonic Neoplasms↗