Biomedical subjects

A Ochiai

Publications and source records attributed to A Ochiai.

At least 163 records · Page 9Linked to original sources

PubMed1989

The effect of phorbol esters on cell growth and epidermal growth factor receptor modulation in a human gastric carcinoma cell line TMK-1.

Tumor promoting phorbol esters, 12-O-tetradecanoylphorbol-13-acetate (TPA) and phorbol-12,13-dibutyrate (PDBu), significantly enhanced the growth of human gastric cancer cell line TMK-1, whilst activating protein kinase C. The time course of 125I-epidermal growth factor (EGF) binding to TMK-1 cells after TPA treatment showed a decrease in the number of EGF receptors on TMK-1 cells within 3 hr. Autophosphorylation of EGF receptor decreased in accordance with the decrease of EGF binding by TPA treatment. Scatchard plot analysis of TMK-1 cells after TPA treatment showed that high affinity EGF receptor disappeared at 3hr but the number of EGF receptors increased at 24 hr. These findings suggest that tumor promoting phorbol esters stimulate the cell growth through activation of protein kinase C and modification of EGF receptor of human gastric cancer cell line TMK-1.

Cell Division↗

PubMed1988

Interaction between epidermal growth factor and its receptor in progression of human gastric carcinoma.

The expressions of epidermal growth factor (EGF) and its receptor were studied immunohistochemically in a total of 156 gastric carcinomas; 26 early and 130 advanced. No EGF immunoreactivity was found in early carcinomas, while EGF-positive tumor cells were detected in 38 (29.2%) of the 130 advanced carcinomas. EGF receptor immunoreactivity was detected in one (3.8%) of the 26 early carcinomas and in 44 (33.8%) of the 130 advanced carcinomas, the incidence being significantly different (p less than 0.01). Out of the 130 advanced carcinomas, 17 (13.1%) had synchronous expression of EGF and its receptor and most of the tumors with strong expression of EGF were positive to EGF receptor. A significant correlation was observed between the depth of tumor invasion and EGF or its receptor immunoreactivity in tumor cells (p less than 0.05). Furthermore, a good correlation was demonstrated between the synchronous expression of EGF and its receptor and the depth of tumor invasion or the tumor staging. The incidence of cases with EGF in metastatic tumors was significantly higher than that in primary tumors (p less than 0.05). Patients with synchronous expression of EGF and its receptor had a far poorer prognosis than those without EGF and receptor.

Adenocarcinoma↗

PubMed1988

Expression of epidermal growth factor receptor in human gastric and colonic carcinomas.

The expression of epidermal growth factor (EGF) receptor was examined immunohistochemically in a total of 122 gastric and 61 colonic carcinomas, out of which 16 gastric and 8 colonic carcinomas were also examined by 125I-labeled EGF binding analysis and Western blotting. The values of EGF binding were 12.68 +/- 1.98 (SE; n = 16) fmol/mg protein in gastric carcinomas and 5.72 +/- 2.15 (n = 8) fmol/mg protein in nonneoplastic gastric mucosa, the difference being significant (P less than 0.01). In the colonic tissue, the binding capacities in carcinomas and nonneoplastic mucosa were 13.29 +/- 4.17 (n = 8) and 10.68 +/- 0.41 (n = 3) fmol/mg protein, respectively. Scatchard analysis of 125I-labeled EGF binding indicated a single class of receptors in gastric and colonic carcinomas with an apparent Kd value of from 111 to 277 (n = 4) and from 87.4 to 341 fM (n = 5), respectively, except for one gastric carcinoma having two classes of receptors (Kd = 15.9 and 896 fM). In Western blotting using monoclonal anti-EGF receptor antibody, various levels of EGF receptor expression were detected in 12 (85.7%) of the 14 gastric carcinomas and in 7 (87.5%) of the 8 colonic carcinomas. Immunohistochemically, EGF receptor immunoreactivity was detected in one (3.8%) of the 26 early gastric carcinomas, while it was observed in 33 (34.4%) of the 96 advanced gastric carcinomas, the incidence between the two being significantly different (P less than 0.01). In the colonic carcinomas, 47 (77.1%) of the 61 cases showed positive immunoreactivity to EGF receptor, which did not differ by histological type.

Carcinoma↗

PubMed1988

Effect of human epidermal growth factor on cell growth and its receptor in human gastric carcinoma cell lines.

The effect of human epidermal growth factor (hEGF) on the growth of various histological types of six human gastric carcinoma cell lines was examined. The cell lines had relatively high affinity EGF receptors (dissociation constant Kd = 10(-9) to 10(-10) M). One gastric cancer cell line, MKN-74 (well differentiated adenocarcinoma) showed no response to hEGF, in cell growth, DNA synthesis or 125I-hEGF cell binding. There were no apparent correlations between histological type and cell growth, DNA synthesis or number of EGF receptors in these cells. The number of EGF receptors and the Kd value of the gastric carcinoma cell lines varied with their internal and external environments. hEGF concentrations corresponding to maximum stimulation in DNA synthesis varied between cell lines. The results suggest some gastric carcinoma cells to have EGF receptors and their growth seemingly to be stimulated by EGF in vitro. There are, however, no obvious correlations between the effect of hEGF on the growth of human gastric carcinoma cell lines or their histological type.

Adenocarcinoma↗

PubMed1987

[Aplastic anemia and occupational factors in Japanese industries].

Four mail questionnaire surveys were conducted on the incidence of aplastic anemia among industrial workers throughout Japan in collaboration with industrial doctors during a period from 1970 to 1983. The following major results were obtained. 1. Response rates were 55.5% (874/1,574 enterprises) in the first mail questionnaire survey in 1970-1972, 65.3% (294/450) in the second survey in 1973, 49.1% (170/346) in the third survey in 1976-1980, and 76.6% (242/316) in the fourth survey in 1981-1983. There was no significant difference in industrial types among the four surveys. 2. The numbers of aplastic anemia patients newly diagnosed were 145 (112 males/33 females) in the first survey, 21 (16/5) in the second survey, 51 (41/10) in the third survey and 30(24/6) in the fourth survey. Incidence rates per million were 14.7 (14.4 males/15.5 females) in the first and second survey, 14.2 (13.5/18.3) in the third survey and 9.1 (8.6/11.9) in the fourth survey. The rates were almost constant from 1970 through 1980, but the rates decreased thereafter. The rate was higher in females than in males, but the difference was not significant. 3. Incidence rates were high in rubber industry (26.8 per million), paper industry (24.8), and petroleum industry (22.5), but there was no industrial type demonstrating a constantly higher incidence in every survey. Manufacturing industries showed a higher incidence (14.6) than nonmanufacturing industries (11.7). 4. By type of work, non-productive work (67.2%), i.e., clerical (30.8%), administrative (8.9%), technical (7.7%), were the main jobs of 247 registered aplastic anemia patients (193 males and 54 females). 5. Thirty patients had been exposed to noxious agents such as organic solvents (21 cases including 3 exposed to benzene), metals (6), and radiation (1). However, in these cases no causal relationship between exposure and disease onset could be demonstrated. 6. Thirty-nine cases had a drug-intake history before onset of the disease. Drugs given included chloramphenicol (4 cases), other antibiotics (4), antituberculosis agents (8), analgesics (6), and tranquillers (4). The results obtained revealed no positive evidence that occupational factors peculiar to Japanese industries were involved in triggering aplastic anemia.

Adult↗

PubMed1987

[A case of primary retroperitoneal tumor with combined histologic features of embryonal carcinoma and yolk sac tumor].

A case of a primary retroperitoneal tumor, combining two histologic features of embryonal carcinoma and a yolk sac tumor is reported. A 31-year-old male complained of severe abdominal pain and had a laparotomy following a diagnosis of acute panperitonitis. During the operation, a large retroperitoneal tumor attached to the abdominal aorta was found, accompanied with remarkable hemorrhage and necrosis. Histologically, the tumor showed immature large cells with a solid pattern, focally forming reticular, tubular and glomeruloid structures. PAS positive hyaline bodies, multinuclear giant cells and mitoses were noted in the tumor cells. Immunohistochemically, the tumor cells in the reticular pattern were positive for alpha-fetoprotein. No abnormality was found in the testes on palpation and ultrasound sonographic examination.

Adult↗

PubMed1987

Immunohistochemical detection of c-myc oncogene product in human gastric carcinomas: expression in tumor cells and stromal cells.

c-myc protein p62 in human gastric carcinomas was studied by immunohistochemistry using an antiserum raised against the C-terminal portion of the human c-myc gene protein. No immunoreactivity of c-myc p62 was detected in tumor cells of 27 early carcinomas, while c-myc p62-positive tumor cells were observed in 51 (36.4%) of the 140 advanced carcinomas. Many stromal cells including macrophages and fibroblasts around the tumors showed various degrees of c-myc p62 immunoreactivity. Localization of c-myc p62 was predominant in the cytoplasm of tumor cells and stromal cells. The prognosis of patients with p62-positive stromal cells was significantly better than that of patients with p62-negative stromal cells.

Epidermal Growth Factor↗

PubMed1987

A case with silent type of pseudo-acholinesterasemia.

One case of pseudo-acholinestrasemia was experienced in our hospital. The patient was a 54-year-old female with sigmoid colon cancer. A preoperative examination showed that her cholinesterase (ChE) level was 7 IU/L (normal range: 3,700-5,400 IU/L) although no abnormalities were found in other enzymes derived from the liver, total protein and albumin level in the serum. An investigation of eight family members over two generations revealed two cases of acholinesterasemia in addition to the patient. Immunological examination by Ouchterlony's method and isoenzyme analysis by polyacrylamide gel electrophoresis showed that ChE production was absent in this case, while dibucaine or fluoride number was normal among the family members. Based on these results, it was concluded that this patient belonged to the silent type of homozygote. A case of pseudo-acholinesterasemia, which is very rare in Japan, is described.

Blood Transfusion↗

PubMed1986

Cholecystokinin inhibition of tumor growth and gastrin-stimulated cyclic adenosine 3':5'-monophosphate metabolism in human gastric carcinoma in nude mice.

This study deals with the effect of four types of COOH-terminal cholecystokinin (CCK) fragments on the growth of xenotransplantable human gastric cancer (SC-6-JCK, a poorly differentiated adenocarcinoma) whose growth has been promoted by pentagastrin. The growth of the tumor was inhibited using daily s.c. injections of CCK-octapeptide (CCK-8) and glutaryl-CCK-8 at a dose of 500 micrograms/kg body weight. After 30 days of treatment with CCK-8 or glutaryl-CCK-8, a significant decrease was observed in the tumor weight (P less than 0.05) and the tumor size P less than 0.01) in comparison with those of the control. But treatment with CCK-12 and pyroglutamyl-CCK-8 did not produce inhibition of tumor growth. Furthermore the correlation between the effect of CCK-8 on the normal rise in tumor cyclic adenosine 3':5'-monophosphate (cAMP) levels caused by pentagastrin injection and tumor growth was studied. The increase of cAMP by a single i.p. injection of pentagastrin at a dose of 20 micrograms/mouse was significantly inhibited by pretreatment with CCK-8 at concentrations equimolar to pentagastrin (P less than 0.05), while cAMP in the tumor was slightly elevated by a single i.p. injection of CCK-8 alone. Also in the in vitro study, CCK-8 inhibited the increase of cAMP and the activation of cAMP-dependent protein kinase which was stimulated by pentagastrin. These results suggest that proliferation of gastrin-dependent human gastric cancers may be suppressed by CCK in competition with gastrin.

Adenocarcinoma↗

PubMed1986

Ha-ras oncogene product in human gastric carcinoma: correlation with invasiveness, metastasis or prognosis.

c-Ha-ras oncogene product in human gastric carcinomas was examined by Western blotting and immunohistochemistry using anti-Ha-ras p21 antibody. In Western blotting, high levels of c-Ha-ras p21s were found in gastric carcinomas. Immunohistochemically, c-Ha-ras p21 was detected in 3 (11.1%) of 27 early carcinomas and in 63 (43.8%) of 144 advanced carcinomas. In advanced carcinomas, c-Ha-ras p21-immunoreactivity was correlated with the depth of tumor invasion and was stronger in metastatic tumors than in primary tumors. Patients with c-Ha-ras p21-positive carcinomas had a significantly worse prognosis than those with p21-negative carcinomas.

Amino Acid Sequence↗

PubMed1986

[Monoclonal antibody 9A3 raised against a human poorly differentiated gastric adenocarcinoma cell line].

A new mouse monoclonal antibody 9A3 (IgGl,K) raised against human poorly differentiated gastric adenocarcinoma cell line TMK-1 was produced. Immunohistochemically, 9A3 antibody reacted strongly with gastric carcinoma, colon carcinoma, pancreas carcinoma, lung carcinoma, breast carcinoma and cervical carcinoma of the uterus. This antibody did not react with various normal tissues from the whole body with the exception of neutrophils and macrophages. In fetal tissues, 9A3 antibody reacted with esophageal mucosa and colon epithelium, but did not react with purified carcinoembryonic antigen (CEA). The molecular weight of the antigen extracted with NP-40 from TMK-1 cells was estimated to be about 46,000 daltons by SDS-PAGE. The 9A3 antigen was also detected in conditioned tissue culture medium of the TMK-1 cell line and sera of gastric cancer patients and tumor imaging could be performed in xenotransplantable human gastric carcinoma in nude mice. In summary, 9A3 antibody may serve as a new marker for detection of cancer by immunohistochemical, cytological techniques and serologically in the sera of cancer patients.

Adenocarcinoma↗

PubMed1985

Pleiotropic phenotypic expression in cybrids derived from mouse teratocarcinoma cells fused with rat myoblast cytoplasts.

Cybrid clones were isolated by fusing mouse embryonal carcinoma (PCC4) cells with cytoplasts of rat myoblastic cells (L6TG X CAPr). Although some clones were similar to PCC4 (Type II), a high proportion (88%) were differentiated; the differentiated cells had a mesh-like arrangement (Type I) or were flat with many projections (Type III). Protein patterns of both Type I and Type III cells changed markedly from that of PCC4 cells. Type III cells lacked alkaline phosphatase and expressed endo A and B proteins predominantly. One Type III clone produced alpha-fetoprotein and plasminogen activator (visceral endoderm-like), while another clone consisted of trophectodermal cell-like giant cells. Therefore it was shown that introduction of the somatic cell cytoplasm induces differentiation of teratocarcinoma stem cells, suggesting a cytoplasmic element (or elements) regulating gene expression.

Alkaline Phosphatase↗

PubMed1985

Growth-promoting effect of gastrin on human gastric carcinoma cell line TMK-1.

A human gastric carcinoma cell line TMK-1 was established in vitro by the soft agar method from SC-6-JCK, a poorly differentiated adenocarcinoma xenotransplanted in nude mice. TMK-1 cells had a doubling time of approximately 35 hr and showed carcinoembryonic antigen (CEA), alpha 1-antitrypsin and secretory component immunoreactivity. Ultrastructurally, the tumor cells were characterized by numerous mitochondria, tubulovesicles and intracytoplasmic canaliculi filled with abundant microvilli. The growth of TMK-1 cells was promoted by 10nM human gastrin (G-17), 2 microM tetragastrin or 2 microM pentagastrin, among which human gastrin showed the most effective growth promotion. Moreover, incorporation of [3H]thymidine into TMK-1 cells was stimulated by gastrin in a dose-dependent manner. The content of cyclic adenosine 3',5'-monophosphate (cAMP) in TMK-1 cells was increased by gastrin treatment but decreased to the control level within 10 min. cAMP-dependent protein kinase was also activated by gastrin administration.

Carcinoma↗

PubMed1985

A monoclonal antibody reacting with various human carcinomas and fetal colon and esophagus.

A monoclonal antibody 9A3 was raised to human gastric carcinoma cell line TMK-1, a poorly differentiated adenocarcinoma of the stomach. 9A3 antibody (IgG1, kappa) strongly reacted with various carcinomas immunohistochemically, but did not react with any normal tissues of the whole body tested except for neutrophiles and macrophages. 9A3 antibody also reacted with the luminal surface of the fetal colon and esophagus at six months of gestation. The antigen recognized by 9A3 antibody might be an oncodevelopmental antigen.

Adenocarcinoma↗

PubMed1985

Calcium-activated, phospholipid-dependent protein kinase in human gastric mucosa and carcinoma.

Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) activities in human gastric mucosa and carcinoma were examined. The bulk of protein kinase C activity was associated with the cytosol in both gastric mucosa and carcinoma. Protein kinase C activity in the soluble fraction in human gastric carcinoma was significantly higher than that in nonneoplastic gastric mucosa (P less than 0.05), the values being 357.7 and 215.3 units/g protein, respectively. On the other hand, cAMP-dependent protein kinase (protein kinase A) activity was decreased slightly in gastric carcinomas. The ratios of protein kinase C to protein kinase A in human gastric carcinoma and nonneoplastic mucosa were 0.849 and 0.435, respectively, the difference being significant (P less than 0.01). In DEAE-cellulose column chromatography, the elution profiles of protein kinases from gastric carcinomas were the same as those from gastric mucosas except that a larger peak of protein kinase C was found. It seems probable that increased protein kinase C activity plays an important role in the growth of human gastric carcinoma as a signal transducer.

Carcinoma↗

PubMed1985

Type I and II cyclic adenosine 3':5'-monophosphate-dependent protein kinase in human gastric mucosa and carcinomas.

Cyclic adenosine 3':5'-monophosphate (cAMP)-dependent and cAMP-independent protein kinase activity and the isoenzyme pattern of cAMP-dependent protein kinase were compared in tissues from human nonneoplastic gastric mucosa, 11 human gastric carcinomas, and 2 xenotransplantable human gastric carcinomas (SC-6-JCK and St-15). No difference in total protein kinase activity could be observed between nonneoplastic gastric mucosa and gastric carcinomas. According to diethylaminoethyl cellulose column chromatography, the isoenzyme pattern of the nonneoplastic gastric mucosa was the same in both the gastric fundus and the antrum, and the activity ratio of type II to type I was 5.01. In gastric carcinomas, the elevation of type I was detected independently of the histological type. In xenotransplantable human gastric carcinomas in nude mice, type I isoenzyme was significantly elevated. The activity ratio of type II to type I was 1.70 in SC-6-JCK carcinomas and 1.81 in St-15 carcinomas, respectively. These results suggest that type I cAMP-dependent protein kinase activity in the stomach may be a biochemical marker for malignant transformation and transplantability of gastric tumors.

Chromatography, DEAE-Cellulose↗

PubMed1984

Effects of gastrin on tumor growth and cyclic nucleotide metabolism in xenotransplantable human gastric and colonic carcinomas in nude mice.

This study deals with the growth effect of gastrin on two xenotransplantable human gastric carcinomas (SC-6-JCK, poorly differentiated adenocarcinoma; and St-15, mucinous adenocarcinoma) and on one colonic carcinoma (Co-3, well-differentiated adenocarcinoma). In SC-6-JCK, the treatment with s.c. injection of pentagastrin at a dose of 10 micrograms/mouse once daily for 25 days promoted the growth of the tumor transplanted in nude mice, but gastrin had no effect at all on St-15 and Co-3. In SC-6-JCK, the weight, size, and labeling index of [3H]thymidine of the tumor were significantly increased in comparison with those of the control (p less than 0.05). In SC-6-JCK, cyclic adenosine 3':5'-monophosphate (cAMP) in the tumor was increased by a single i.p. injection of pentagastrin at a dose of 20 micrograms/mouse in nude mice, but such an increase was not observed in St-15 and Co-3. Cyclic guanosine 3':5'-monophosphate in SC-6-JCK was slightly increased by gastrin treatment but was not affected in the other tumors. In SC-6-JCK, at 30 min after gastrin treatment when cAMP showed a maximum increase, the activity ratio of cAMP-dependent protein kinase in the tumor was also elevated. In vitro also, gastrin stimulated cAMP production and cAMP-dependent protein kinase activation. The data suggest that some human gastric carcinomas may have receptor for gastrin.

Adenocarcinoma↗

PubMed1984

Secretory component and immunoglobulin in human gastric carcinoma: an immunohistochemical study.

The occurrence of secretory component (SC), IgA, IgG and IgM within tumor cells was immunohistochemically examined in a total of 101 gastric carcinomas comprising 50 early cancers and 51 advanced cancers. In advanced cancers, the frequency of SC was significantly higher in well-differentiated adenocarcinoma than in poorly differentiated adenocarcinoma. The frequency of IgA did not differ with stage of cancer, but the frequencies of IgG and IgM were significantly higher in advanced cancer than in early cancer. The immunoglobulin-producing plasma cells in the stroma of advanced cancer were chiefly IgG, followed by IgA and IgM producers. The intensity of IgA plasma cell infiltration correlated with presence of IgA in tumor cells. No correlation was noted between serum immunoglobulin value and immunoglobulin in tumor cells. The survival rate indicated a tendency for IgG-containing advanced cancers which were infiltrated with many IgG plasma cells to have a better prognosis.

Adenocarcinoma↗