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Biomedical subjects

W Yasui

Publications and source records attributed to W Yasui.

At least 127 records · Page 7Linked to original sources
PubMed1995

[Expression of sdi1, a potent inhibitor of cdk2 kinase, cdk2 and G1 cyclins and mutation of sdi1 in human gastric carcinomas].

Sdi1, also known as Cip1/Waf1, is a potent inhibitor of G1 cyclin-dependent kinases, which is induced by wild type p53 but not by mutant p53. Expression of mRNAs for sdil, cdk2 and G1 cyclins was examined in gastric carcinomas. All the cell lines expressing very low or undetectable level of sdil mRNA contains p53 gene abnormalities, while the cell lines expressing high level of sdil shares wild type p53 gene. An exception was a cell line MKN-28 with mutated p53 gene which expressed mRNAs for sdi1, cdk2 and G1 cyclins at high levels, p21 point mutation was detected in one (MKN-28) of the eight cell lines. These result suggest that low level of sdil and subsequent overexpression of cdk2 and G1 cyclins might be involved in deregulated growth of gastric carcinomas. It is likely that gene alteration of sdil and subsequent loss of function may have implication for cdk2 and G1 cyclins expression.

CDC2-CDC28 Kinases↗
PubMed1995

Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions.

Recent evidence indicates that telomerase activity may be necessary for cell immortality, which is required for the sustained and indefinite growth of most malignant cells. We analyzed telomerase activity in gastric and colorectal cancers and in gastric and colorectal precancerous lesions to determine whether malignant progression depends on the activation of telomerase and at what stage of carcinogenesis cells have detectable telomerase activity. Telomerase activity was measured by the telomeric repeat amplification protocol assay and was detected in 17 (85%) of 20 primary gastric carcinoma tissues and in 19 (95%) of 20 primary colorectal carcinomas, regardless of tumor staging and histological types. All nodal metastases, peritoneal metastases, and a recurrent gastric cancer tumor were positive. All cell lines established from gastric and colorectal cancers contained telomerase activity. In precancerous lesions, 10 (100%) of 10 colorectal tubular adenomas were telomerase positive, in addition to 3 (23%) of 13 gastric intestinal metaplasias and 1 (50%) of 2 gastric adenomas, whereas the corresponding gastric normal mucosas as well as colorectal mucosas were negative. These results indicate overall that reactivation of telomerase may occur at an early stage of carcinogenesis and may correlate well with malignant progression of gastric cancer. Telomerase activity thus may serve as a powerful additional tool for cancer diagnosis.

Adenocarcinoma↗
PubMed1994

Frequent loss of heterozygosity of the long arm of chromosome 7 is closely associated with progression of human gastric carcinomas.

Loss of heterozygosity (LOH) on the long arm of chromosome 7 was examined using 5 polymorphic marker probes on 98 gastric carcinomas to elucidate a novel locus for development and progression of the tumors. Twenty-six (32%) of 82 informative cases showed LOH on 7q on at least one locus of 5 loci. Among 5 loci, LOH at D7S95 locus was most frequent, the incidence being 53% in well-differentiated gastric carcinomas and 33% in poorly differentiated and scirrhous gastric carcinomas respectively. At 3 loci, c-met, D7S63 and D7S22, the incidence of LOH was about 30% and 10% in well-differentiated and poorly differentiated gastric carcinoma cases respectively. In contrast, LOH at D7S64 was not detected in any gastric-carcinoma cases. Deletion mapping of 7q revealed that D7S95 locus was the essential region of LOH. Eight (62%) of 13 cases with LOH at D7S95 locus belonged to the most advanced stage grouping. Furthermore, 6 (75%) of 8 cases with abdominal dissemination showed LOH at D7S95. Therefore, cases with LOH at D7S95 showed significantly worse prognosis than the cases without the LOH in the stage-III and stage-IV groups. These findings overall suggest that D7S95 locus on 7q may contain a candidate suppressor gene for the progression of gastric carcinoma.

Adenocarcinoma↗
PubMed1994

Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers.

Nearly 10% of cancer patients develop a second primary cancer within 10 years after surgical removal of the first tumor. Hence, detection of a genetic risk for developing multiple primary tumors would be of clinical importance. To investigate whether a genetic defect(s) involving the mismatch repair system constitutes an important risk factor in patients with multiple primary cancers, we examined replication errors (RER) at microsatellite loci in 79 primary cancers which had developed among 38 patients with multiple primary cancers. The RER(+) phenotype was observed at five microsatellite loci on chromosomes 2, 3, 11, or 17 in tumors from 34 (89%) of 38 patients with multiple primary cancers but only in 19 tumors from 174 patients (11%) with a single primary cancer. Our results suggested that: (a) genetic instability may play an important role in development of multiple primary cancers, and (b) testing for RER in a primary cancer may be an appropriate approach to detection of patients at high risk for developing multiple primary cancers.

DNA Repair↗
PubMed1994

Expression of a 31-kDa lactoside-binding lectin in normal human gastric mucosa and in primary and metastatic gastric carcinomas.

The expression of lactoside-binding lectin L-31 was analyzed in normal mucosa and in primary and metastatic gastric carcinomas. Immunoblotting revealed L-31 lectin in extracts of normal and malignant gastric tissues from 26 patients. The L-31 level was higher in tumor than in normal tissue in 9/26 cases, similar in 14/26 cases, and lower in 3/26 cases. Anti-L-31 monoclonal antibodies (MAbs) were used in immunohistochemical analyses to compare lectin expression in specimens of primary gastric carcinomas and adjacent normal mucosa from 39 patients and in specimens of metastases and the corresponding primary gastric carcinomas from 74 patients. The lectin was detected in normal gastric epithelial cells and in all gastric carcinoma specimens, albeit in varying amounts. The L-31 level was significantly higher in the primary tumor than in adjacent normal tissue in 55% of the well-differentiated tubular carcinoma cases and in 50% of stage-III and -IV tumors. L-31 expression in liver metastases from well-differentiated tubular primary gastric carcinomas was higher in 31% of the cases relative to the corresponding primary cancers. Likewise, L-31 expression in metastases from poorly differentiated gastric carcinomas in lymph nodes was higher in 38% of the cases compared to the primary cancers. The higher expression of L-31 in primary cancers and metastases of certain types implicates this lectin in the metastatic phenotype, but the presence of L-31 in a primary cancer is not sufficient to allow the metastatic propensity of the tumor to be predicted.

Antibodies, Monoclonal↗
PubMed1994

Effect of hepatocyte growth factor on the expression of E- and P-cadherin in gastric carcinoma cell lines.

Hepatocyte growth factor (HGF), identical to scatter factor, (SF) is a secretory glycoprotein from fibroblasts which dissociates and increases the motility of various types of epithelial cells. After treatment of three gastric carcinoma cell lines (MKN-28, MKN-45 and TMK-1) with HGF (10 ng/ml), TMK-1 cells lost their tight cell to cell contact and showed marked scattering, while the two other cell lines remained unaffected. To learn about the underlying mechanism of the HGF induced scattering, we examined the expression of adhesion molecules and growth factor/receptor systems at the mRNA and protein level. The observed scattering of treated TMK-1 cells was associated with a reduction in the expression of E- and P-cadherin protein. The respective mRNA levels remained unchanged after HGF/SF treatment. In the two other cell lines, which showed no scattering, there were no changes in the expression of E- and P-cadherin. All other growth factors and their receptors examined (TGF-alpha, EGFR, c-met and c-erbB2) remained constant and were not affected by HGF treatment. The results suggest that HGF/SF may regulate cell adhesion in gastric carcinomas via E- and P-cadherin expression at the protein level.

Adenocarcinoma↗
PubMed1994

Metabolic adaptation of skeletal muscles to gravitational unloading.

Responses of high-energy phosphates and metabolic properties to hindlimb suspension were studied in adult rats. The relative content of phosphocreatine (PCr) in the calf muscles was significantly higher in rats suspended for 10 days than in age-matched cage controls. The Pi/PCr ratio, where Pi is inorganic phosphate, in suspended muscles was less than controls. The absolute weights of soleus and medial gastrocnemius (MG) were approximately 40% less than controls. Although the % fiber distribution in MG was unchanged, the % slow fibers decreased and the % fibers which were classified as both slow and fast was increased in soleus. The activities (per unit weight or protein) of succinate dehydrogenase and lactate dehydrogenase in soleus were unchanged but those of cytochrome oxidase, beta-hydroxyacyl CoA dehydrogenase, and citrate synthase were decreased following unloading. None of these enzyme activities in MG changed. However, the total levels of all enzymes in whole muscles decreased by suspension. It is suggested that shift of slow muscle toward fast type by unloading is associated with a decrease in mitochondrial biogenesis. Further, gravitational unloading affected the levels of muscle proteins differently even in the same mitochondrial enzymes.

Animals↗
PubMed1994

Expression of cripto in human pancreatic tumors.

The expression of cripto gene product was examined immunohistochemically in 45 surgically resected pancreatic tumors, including 32 invasive ductal carcinomas, 4 intraductal papillary adenocarcinomas, 4 intraductal papillary adenomas, 2 mucinous cystadenomas, 2 islet cell tumors, and one solid and cystic tumor, and compared with that in 32 areas of accompanying chronic pancreatitis present in the cases of invasive ductal carcinomas and 5 non-tumorous areas of pancreas without pancreatitis. All pancreatic ductal tumors including adenomas and carcinomas showed positive staining with no difference in terms of staining intensity among intraductal tumors and invasive carcinomas with or without mucin hypersecretion. Islet cell tumors were positively stained but the solid and cystic tumor was negative. Duct epithelial cells and acinar cells were negative but islet cells were positive in the pancreas tissues without pancreatitis. Cells arranged in duct-like structures in areas of accompanying chronic pancreatitis were positively stained. The results suggest that cripto expression might be associated with a growth advantage of tumor cells and also with differentiation to form duct-like structures.

Biomarkers, Tumor↗
PubMed1994

Loss of heterozygosity at the bcl-2 gene locus and expression of bcl-2 in human gastric and colorectal carcinomas.

The loss of heterozygosity (LOH) at the bcl-2 gene locus and the expression of the bcl-2 gene were examined in gastric and colorectal carcinoma cell lines and carcinoma tissues. LOH at the bcl-2 locus was detected in 24% (4/17) of gastric and 60% (6/10) of colonic carcinomas, all of which were well differentiated adenocarcinomas, whereas LOH was not seen in poorly differentiated ones. On the other hand, 24% (5/21) of poorly differentiated stomach cancers overexpressed bcl-2 gene, whereas no overexpression was detected in well differentiated stomach cancer. Three gastric and three colorectal carcinoma cell lines, all of which were derived from poorly differentiated adenocarcinomas, expressed considerable levels of bcl-2 mRNA and protein. These results suggest that LOH at the bcl-2 locus is frequently associated with well differentiated adenocarcinomas of the stomach and colon, and bcl-2 overexpression has implications for the development of poorly differentiated adenocarcinomas of the gastrointestinal tract.

Adenocarcinoma↗
PubMed1994

Responses of beta-adrenoceptor in rat soleus to phosphorus compound levels and/or unloading.

Responses of beta-adrenoceptor (beta-AR) in rat soleus to gravitational unloading and/or changes in the levels of phosphorus compounds by feeding either creatine or its analogue beta-guanidinopropionic acid (beta-GPA) were studied. A decrease in the density of beta-AR (about -35%) was induced by 10 days of hindlimb suspension, but the affinity of the receptor was unaffected. Suspension unloading tended to increase the levels of adenosine triphosphate and phosphocreatine and decrease inorganic phosphate. Even without unloading, the beta-AR density decreased after an oral creatine supplementation (about -20%), which also tended to elevate the high-energy phosphate levels in muscle. However, an elevation of beta-AR density was induced (about +36%) after chronic depletion of high-energy phosphates by feeding beta-GPA (about +125%). Data suggest that the density of beta-AR in muscle is elevated if the high-energy phosphate contents are chronically decreased and vice versa. However, it may not be directly related to the degree of muscle contractile activity.

Animals↗
PubMed1994

Responses of contractile properties in rat soleus to high-energy phosphates and/or unloading.

Responses of contractile properties of soleus to unloading and/or changes in high-energy phosphate contents were studied in rats. Reduction of high-energy phosphates, especially phosphocreatine, in ankle extensors was induced by feeding beta-guanidinopropionic acid (beta-GPA). The major finding in the study was that the fatigability and speed-related contractile properties responded to unloading and creatine supplementation in a similar manner. The high-energy phosphate contents tended to be elevated after 10-d supplementation of creatine and hindlimb suspension. The shift toward slow-type, mainly due to an increased one-half relaxation time, was seen in rats fed beta-GPA. Such a shift was reversed by feeding creatine or by hindlimb suspension; however, the suspension-induced shift of contractile properties toward fast-type was not prevented completely by beta-GPA feeding. Although the muscle fatigue resistance did not change by beta-GPA feeding alone, the decrease in fatigue resistance following suspension and creatine supply was less in the beta-GPA group. It is suggested that the levels of high-energy phosphates and tension production play important roles in the regulation of contractile properties of the soleus muscle.

Animals↗
PubMed1994

Non-insulin and non-exercise related increase of glucose utilization in rats and mice.

The effects of high-energy phosphate contents in muscles on glucose tolerance and glucose uptake into tissues were studied in rats and mice. Enhanced glucose tolerance associated with depleted high-energy phosphates and elevated glycogen content in muscles and liver was observed in animals fed creatine analogue beta-guanidinopropionic acid (beta-GPA). Distribution of infused 2-[1-14C]deoxy-D-glucose in tissues especially in the soleus muscle, kidney, and brain was greater in mice fed beta-GPA than controls. The glucose uptake was decreased when the contents of ATP and glycogen were normalized following creatine supplementation. Plasma insulin in animals at rest was lower and its concentration after intraperitoneal glucose infusion tended to be less in animals fed beta-GPA than controls (p > 0.05), although the pattern of insulin response to glucose loading was similar to the control. The daily voluntary activity in beta-GPA fed mice was also less than controls. These results suggest that improved glucose tolerance is not related to elevated insulin concentration and/or decreased glycogen following exercise. Such improvement may be due to an increased mitochondrial energy metabolism caused by depletion of high-energy phosphates.

Animals↗
PubMed1994

Gene alterations in intestinal metaplasia and gastric cancer.

PURPOSE: To review genetic alterations in precancerous lesions and adenocarcinoma of the stomach. RESULTS: Telomere reduction, tpr-met oncogenic rearrangement, overexpression of cripto, p53 mutations, adenomatous polyposis coli gene mutations and K-ras mutations, which are frequently associated with the well differentiated or intestinal type of stomach cancer, were found in intestinal metaplasia and adenoma of the stomach. CONCLUSIONS: Among these genetic alterations, reduction of telomere repeat arrays might be the initial step in the genetic instability of stomach carcinogenesis. Some of the well differentiated type stomach cancers may develop by an accumulation of multiple gene changes similar to those of colorectal cancer.

Base Sequence↗
PubMed1994

[Genetic characteristics of scirrhous gastric carcinomas].

Genetic characteristics of scirrhous gastric carcinomas are overviewed. Scirrhous carcinomas of the stomach frequently show amplification of c-met and K-sam oncogenes as well as overexpression of 6.0 kb c-met abnormal transcript. For the formation of productive fibrosis and the diffuse infiltrative growth pattern of this malignancy, the essential factors would be not only the loss of cell adhesion molecule function through depressed expression or loss of cadherin or catenin, but also the synchronous overexpression of growth factors from the cancer cells including TGF-beta, PDGF, IGF-II and basic FGF with intimate cancer-stromal interaction through paracrine loop of IL-1 alpha/HGF system.

Adenocarcinoma↗
PubMed1994

[Molecular diagnosis on gastrointestinal cancers].

Many of the genetic alterations related to carcinogenesis and progression such as gene amplification, deletion, mutation and overexpression can be analyzed on paraffin-embedded clinical materials. Genetic abnormalities of tumor suppressor gene such as p53 and APC (adenomatous polyposis coli) are good markers for differential diagnosis of gastrointestinal cancers. Gene amplification and overexpression of oncogenes and growth factors/receptors such as c-met, K-sam, c-erbB2, EGF and EGF receptor are biological marker of biological malignancy. Molecular diagnosis has been done in Hiroshima Medical Association Laboratory to make an objective diagnosis for border line lesions and to obtain information on the biological behavior of gastrointestinal cancers based on genetic alterations. Molecular analysis is a powerful tool to complement histological diagnosis of gastrointestinal lesions.

Gastrointestinal Neoplasms↗