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Biomedical subjects

T Kamata

Publications and source records attributed to T Kamata.

At least 181 records · Page 10Linked to original sources

In vitro tyrosine phosphorylation studies on RAS proteins and calmodulin suggest that polylysine-like basic peptides or domains may be involved in interactions between insulin receptor kinase and its substrate.

We have investigated the in vitro tyrosine phosphorylation of the HRAS and KRAS proteins by human placental insulin receptor kinase. Purified HRAS proteins are not phosphorylated by purified insulin receptor kinase. Since the tyrosine phosphorylation of calmodulin by the insulin receptor kinase in vitro requires cofactors such as protamine and poly(L-lysine), we examined the possibility that poly(L-lysine) may also potentiate the interaction between RAS proteins and the insulin receptor. We found that purified HRAS proteins are indeed phosphorylated by purified insulin receptor kinase in the presence of poly(L-lysine). In contrast, the KRAS protein, which carries an extremely basic domain (residues 172-182, Lys-Asp-Glu-Lys6-Ser-Arg), is phosphorylated by the receptor kinase without the addition of basic proteins. We then determined whether the KRAS basic domain peptide plays a role similar to that of poly(L-lysine) and found that both the HRAS protein and calmodulin are phosphorylated by the receptor kinase in the presence of the KRAS basic domain peptide. Further examination of the role of poly(L-lysine) in potentiating tyrosine phosphorylation of the HRAS protein and calmodulin by purified insulin receptor kinase indicates that poly(L-lysine) affects the conformation of these protein substrates as well as that of the receptor kinase domain. These studies suggest that polylysine-like basic proteins or domains are required to establish the interaction between insulin receptor kinase and its substrate.

Calmodulin↗

Epidermal growth factor receptor status and S-phase fractions in gastric carcinoma.

The correlation with epidermal growth factor (EGF) receptor expression and clinicopathologic findings were studied in 242 gastric carcinomas. They were stained for EGF receptor by means of an immunohistochemical technique using a monoclonal antibody against the receptor. S-Phase fractions were measured by in vivo bromodeoxyuridine (BrdU) labeling and indirect immunohistochemical staining using anti-BrdU monoclonal antibody. In normal gastric epithelium, EGF receptor immunoreactivity could not be found. EGF receptor was found in 76 (31.4%) of 242 gastric carcinomas. Diffusely infiltrating types of carcinomas were more likely than localized tumors to be EGF receptor-positive. In addition, EGF receptor-positive tumors had significantly higher values of BrdU labeling indices than EGF receptor-negative tumors. The patients with EGF receptor-positive carcinomas also had a poorer prognosis than did negative cases. These results suggested that EGF receptor-positive tumors may have higher proliferative activity and local extension may progress more rapidly, and also seem to show that EGF receptor status may possibly be a useful prognostic marker for gastric carcinomas.

Bromodeoxyuridine↗

[Bromodeoxyuridine labeling index in gastric cancer].

In vivo and in vitro BrdU labeling index (L.I.) were calculated in 97 and 11 gastric cancers, respectively. Biopsied specimens by means of endoscopy were used in vitro method. A comparison of the in vitro and in vivo L.I. showed good correlation (p less than 0.01). Gastric cancer with lymph node metastasis had a significantly higher median in vivo L.I. of 16.2% as compared with a median in vivo L.I. of 13.3% in gastric cancer without lymph node metastasis (p less than 0.05). An in vivo L.I. of gastric cancer with vessel invasion was significantly higher than that without vessel invasion (p less than 0.05). Early gastric cancer with an in vivo L.I. of less than 12% had no lymph node metastasis. On the contrary, 31% in that with an in vivo L.I. of greater than 12% had lymph node metastasis. The in vitro L.I. which was similar to the in vivo L.I. may be useful to decide operative procedure in gastric cancer, specially in early gastric cancer.

Bromodeoxyuridine↗

[Stress analysis at the metal-enamel junction of the anterior adhesive bridge on non-prepared teeth with three dimensional photoelastic experiment].

To study the dynamic action at the metal-enamel junction of an adhesive bridge, the author calculated the values of principal stress and maximum shearing stress, and determine the stress distribution at the junction of the adhesive bridge, for which an unprepared central incisor and a canine were used as abutments for a defect of the maxillary lateral incisor, using a three-dimensional photoelastic experiment. Two models were produced for the experiment on the basis of assumed intercuspal position: Model 1 with a loading point set around the incisal edge and model 2 with a loading point at the lingual cingulum. The results were as follows. (1) In both Models, tensile stress was distributed as the principal stress at the metal-enamel junction, except for the loading point, in the adhesive bridge of the non-prepared type. (2) The maximum principal stress was observed in compressive stress at the loading point in the central incisor of Model 2, being 720 kgf/cm2. Model 2 tended to show a higher concentration of stress at the loading point than Model 1. (3) Values of compressive stress at the loading point of the central incisor and canine were compared in Models 1 and 2. The central incisor showed higher stress values than the canine in both models; the canine had 50-60% of the stress values in the central incisor. (4) Investigation of distribution of the maximum shearing stress revealed a value of 360 kgf/cm2 on the surface directly under the loading point of the central incisor and 240 kgf/cm2 at the loading point of the canine in Model 2, and 215 kgf/cm2 at the loading point of the central incisor and 120 kgf/cm2 at the loading point of the canine in model 1. These values were all above the shearing stress of adhesive resin cement.

Dental Alloys↗

[A case of liver metastasis of gastric cancer which was made resectable by hypertheromo-chemo-radiotherapy].

A 60-year-old woman was diagnosed as having liver metastasis from gastric cancer 14 months after total gastrectomy and total pancreatectomy. The liver tumor was so huge and the complication, diabetes mellitus, was so severe that she was palliatively treated by hyperthermo-chemo-radiotherapy (HCR therapy) with 8-MHz capacitive heating system. Because hyperthermia for deep seated tumor is very difficult, irradiation (10 MV X-ray, 36 Gy) and systemic chemotherapy (CDDP, MMC) were combinedly used. After 10 session of hyperthermia, the tumor showed a remarkable regression in size, followed by S8 subsegmentectomy of the liver. Histologically, cancer cells were still viable in the midst of fibrosis around coagulation necrosis, while normal liver cells remained intact. Multidisciplinary HCR therapy is quite a useful modality for liver tumors and may serve to expand the indication for surgical operation.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical significance of serum NCC-ST 439 as a tumor marker for colorectal cancer].

Clinical significance of preoperative serum NCC-ST 439 level was studied in 119 cases of colorectal cancer (90 of primary, 29 cases of recurrent). The positive rates for serum NCC-ST 439 were 28.9% in primary and 65.5% in recurrent cases. The false positive rates for benign disease were 5.6%. These rates were low when compared with those for other tumor markers. The positive rates for serum NCC-ST 439 exhibited a strong correlation with wall invasion, lymph node and liver metastases. A combination assay of NCC-ST 439, CEA and CA 19-9 produced a high positive rates as 43.3% in primary and 86.2% in recurrent cases. These results demonstrate that measurement of serum NCC-ST 439 may be useful for cancer staging and improves the diagnostic rate in combination with CEA and CA 19-9.

Adenocarcinoma↗

Role of membrane glycoproteins in the interaction of blood platelets with the vessel wall--the study on platelet adhesion to in vitro cultured subendothelial matrix.

Adhesion of platelets to the subendothelium is an essential step in hemostasis and thrombosis. Several receptors for adhesive macromolecules have been identified on platelets and are included in the integrin family. To clarify the role of platelet membrane glycoproteins in the interaction of platelets with the subendothelium, 51Cr-labeled platelet adhesion assay and antibody-blocking experiments were performed by using in vitro cultured subendothelium under the static condition. The platelet adhesion in this assay was inhibited by anti-GPIa (VLA-2), GPIc (VLA-5) and -GPIc'-(VLA-6) antibodies, while anti-GPIb and -GPIIb/IIIa antibodies had no effect. Platelets from the patients with Glanzmann's thrombasthenia could also attach to the subendothelium, whereas those from a patient whose platelets lacked GPIa failed to attach to the extracellular matrix (ECM). The monoclonal antibodies against fibronectin and laminin which recognized the cell binding domain of these molecules inhibited the platelet adhesion when they were pre-treated with ECM. Furthermore, antibody-blocking experiments revealed that the percent inhibition by the combination of anti-GPIa, -GPIc and -GPIc' antibodies used herein was approximately 75%. They did not completely inhibit the attachment. These results suggest that the interactions of collagen, fibronectin and laminin with their receptors on platelets are involved in the mechanism of platelet adhesion to subendothelium.

Blood Vessels↗

[Monoclonal antibody NCC-ST-439 in gastric cancer tissue].

An immunohistochemical study revealed that NCC-ST-439 positive tumor were detected in 33% of the 244 gastric carcinomas. The incidence of NCC-ST-439 immunoactivity in well differentiated adenocarcinomas (papillary and tubular adenocarcinoma) was significantly higher than in poorly differentiated adenocarcinomas (including signet-ring cell and mucinous adenocarcinoma). Moreover, NCC-ST-439 immunoreactive tumors showed more frequent vessel invasion and higher DNA content than non-reactive tumors. The recurrence rates of NCC-ST-439 immunoreactive tumors in the liver and lymph nodes were significantly higher than those of non-reactive tumors. Patients with NCC-ST-439 immunoreactive carcinoma had much worse prognosis than those with NCC-ST-439 non-reactive carcinoma. These results suggest that NCC-ST-439 antigen produced by tumor cells plays an important role in the invasive growth and vessel invasion and also serves as a biological marker of malignancy in patients with gastric cancer.

Adenocarcinoma↗

[DNA ploidy pattern in diffuse infiltrating carcinomas of the stomach].

Analysis of DNA ploidy patterns was performed on 76 diffusely infiltrating carcinomas of the stomach and the results correlated with histologic findings and outcome. Twenty six cases were diploid (34%) and 50 cases were aneuploid. There was no correlation between DNA ploidy and histologic type, depth of invasion, lymphatic invasion, evidence of peritoneal dissemination or curability. In aneuploid tumors, incidence of vascular invasion was significantly higher than that in diploid tumors (p less than 0.05). In addition, the patients with aneuploid tumors had a poor prognosis than with diploid tumors. These results indicate that DNA ploidy patterns may possibly be a useful prognostic marker for diffusely infiltrating carcinomas of the stomach.

Aneuploidy↗

Correlation of DNA ploidy and proliferative activity in human gastric cancer.

Analysis of DNA ploidy patterns was performed on 129 cases of primary gastric cancer and the results were correlated with histologic findings and in vivo bromodeoxyuridine (BrdU) labeling. Forty-nine cases were diploid (38%) and 80 cases were aneuploid (62%). There was no correlation between DNA ploidy and histologic type. In aneuploid tumors, 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 to 10 years, 23 of 40 patients (55%) with aneuploid tumors died of disease within 3 to 120 months. Only 13 of 36 patients (36%) with diploid tumors died of disease. The BrdU labeling indices (BrdU LI) ranged 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%. The mean BrdU LI of advanced cancers was 11.9%. The BrdU LI of cancers with lymphatic invasion or lymph node metastasis was higher than those without them. The mean BrdU LI of diploid cancers was 6.0%. The mean BrdU LI of aneuploid cancers was 11.9%. There was a good correlation between BrdU LI and DNA ploidy patterns. These results indicate that DNA ploidy patterns and BrdU LI may possibly be useful prognostic markers for gastric cancers.

Bromodeoxyuridine↗

DNA ploidy pattern and tumour spread in gastric cancer.

The DNA ploidy pattern of gastric cancer was studied in 58 patients to investigate the heterogeneity between primary tumour and metastases. In both primary tumours and lymph node metastases, diploid patterns accounted for 33 per cent, whereas all liver metastases were aneuploid. The percentage of polyploid cells was higher in the liver metastases than in primary tumours and lymph node metastases. When the heterogeneity of DNA ploidy pattern between primary tumour and metastasis was evaluated, diploid tumours had a significantly lower rate of lymph node metastasis heterogeneity than aneuploid tumours. When the DNA ploidy pattern and survival were evaluated, the patients who had a diploid pattern in both primary tumour and metastasis had a significantly higher survival rate than the patients who had an aneuploid pattern in the primary tumour and metastasis (57 per cent versus 26 per cent at 5 years). These data suggest that cell heterogeneity is a common phenomenon in gastric cancer, and this may be important in the evolution of the disease. Furthermore, the role of the DNA ploidy pattern as a prognostic factor is emphasized.

DNA, Neoplasm↗

DNA ploidy in early gastric cancer and its relationship to prognosis.

The relationship between DNA ploidy and clinical prognosis was determined in 65 patients who underwent gastroectomy for early gastric cancer. Of the 65 patients, 16 had intramucosal and 49 submucosal tumours. Five-year survival rates were 100 and 79.6% for patients with intramucosal and submucosal tumours respectively. Diploid tumours were observed more frequently among the patients with intramucosal neoplasms. Among the patients with submucosal invasion, the presence of polyploid cells (greater than or equal to 6c) in less than 10% of the malignant population was associated with a superior survival at 5 years, than those with greater than or equal to 10% of polyploid cells (92.1% vs. 36.3%). When the macroscopic type and the ploidy status were evaluated together, patients who had greater than or equal to 10% of cells with DNA greater than or equal to 6 c and a protruding type of tumour, had a 5 year survival rate of only 12.5%. Finally when factors such as the level of wall invasion, percentage of polyploid cells, type of histogram, and macroscopic type were evaluated by multiple regression analysis, macroscopic type and percentage of polyploid cells were the only significant prognostic factors. On the basis of these findings, the DNA ploidy pattern and the macroscopic type may be useful markers of patients who will develop recurrence.

Biomarkers, Tumor↗