Biomedical subjects

I Okayasu

Publications and source records attributed to I Okayasu.

169 records · Page 10Linked to original sources

PubMedDate not supplied

Cyclin D1 overexpression in invasive breast cancers: correlation with cyclin-dependent kinase 4 and oestrogen receptor overexpression, and lack of correlation with mitotic activity.

BACKGROUND: Cyclin D1 (CCND1) and its catalytic partner cyclin-dependent kinase 4 (cdk4) are known to play important roles in the G1/S check point of the cell cycle, and CCND1 overexpression has been reported to correlate with progression and prognosis of breast cancers. Oestrogen receptor (ER) levels determine the proliferative response to oestrogen by regulating binding. It has been postulated that CCNDI and cdk4 exert effects on mammary carcinogenesis in co-operation with ER. PATIENTS AND METHODS: CCND1 and cdk4 overexpression in 117 breast cancer cases with long-term follow-up were investigated by means of immunohistochemistry and differential polymerase chain reaction (PCR), using formalin-fixed and paraffin-embedded samples, and compared with ER status and mitotic indices. Additional Western blotting and reverse transcription (RT)/PCR/Southern blot hybridization were performed for 4 breast cancer cell lines and 15 fresh-frozen breast cancer samples to confirm CCND1 and cdk4 data. RESULTS: Immunohistochemically 27 cases were CCND1-positive (23.0%), and CCND1 amplification was evident in 21 (21/86; 24.4%). The two methods in combination demonstrated 37 cases (31.6%) to be positive for CCND1 overexpression. Western blotting revealed 60% of samples of fresh tissue to overexpress CCND1, corresponding well with the results of RT-PCR. There was thus a strong discrepancy between results for paraffin block and fresh samples, probably because of the short life of CCND1. In the case of cdk4, the respective percentages for positive cases were 54.7% and 73%. CCND1 and cdk4 overexpression (P < 0.0001), and CCND1 and ER positivity (P = 0.0128) correlated. In addition, samples overexpressing CCND1, cdk4 and ER tended to have slightly lower proliferative activity than samples where these were absent. However, no association with clinicopathological parameters was evident. cdk4 overexpression had no linkage with ER status or clinicopathological status. Neither CCND1 nor cdk4 expression affected prognosis. CONCLUSION: CCND1 overexpression does not correlate with cancer progression or prognosis or with mitotic activity. The results may suggest that an excess accumulation of CCND1 in breast cancer cells tends to suppress entry into the S phase of the cell cycle.

Blotting, Western↗

PubMedDate not supplied

Bacterial invasion into the colonic mucosa in ulcerative colitis.

This study investigated interactions between mucosal lesions and bacterial invasion in ulcerative colitis using the acridine-orange staining method. In all 16 cases of ulcerative colitis, the mucosa was found to be invaded by small rods and cocci. In five of 10 controls, bacteria were seen only adhering to the mucosa and no bacteria were detected in the five remaining cases. It is suggested that the presence of bacteria in the colonic mucosa may be a factor responsible for the persistence or aggravation of ulcerative colitis.

Acridine Orange↗

PubMedDate not supplied

Apoptosis and proliferative activity of non-Hodgkin's lymphomas: comparison with expression of bcl-2, p53 and c-myc proteins.

In order to clarify the role of spontaneous apoptosis of non-Hodgkin's lymphomas in the growth regulation system, apoptotic indices (AI) assessed by DNA nick end-labeling and proliferative activity, estimated in terms of KI-67 labeling indices (KI) and mitotic indices (MI), were compared. In addition, expression of bcl-2, p53 and c-myc was also examined in relation to these indicators. For this study, 103 lymphoma cases were used, comprising 72 of B cell and 31 of T cell origin (42 nodal and 62 extranodal). AI, KI and MI were significantly increased in line with bcl-2 negativity and p53 positivity, and there was no relation to the T, B cell classification or expression of c-myc. These indicators positively correlated overall. Positive correlation was stricter in groups believed to represent a good prognostic predictive factor, such as B cell origin, bcl-2(+), p53(-) and c-myc(-). Significant cross-correlation was noted only between bcl-2 versus T, B cell classification. However, no inverse correlation between bcl-2 and p53 was evident. These results suggest, in non-Hodgkin's lymphomas, that apoptosis plays an important role together with proliferative activity in counter-balancing tumor volume, and is strictly linked to bcl-2 expression, less so to p53 expression, but independent of T, B cell classification and c-myc expression. Apoptotic indices may be a predictive indicator for prognosis similar to proliferative activity.

Apoptosis↗

PubMedDate not supplied

Significance of p27 as a predicting marker for medroxyprogesterone acetate therapy against endometrial endometrioid adenocarcinoma.

We reported that p27 induced by medroxyprogesterone acetate (MPA) may be involved in the progestin-induced growth suppression of human endometrial adenocarcinoma cells. This study aimed at investigating whether p27 expression could be a predicting marker to evaluate the effectiveness of MPA therapy. The clinical responses of 15 patients with endometrial carcinoma treated with MPA were examined. p27 expression was evaluated by immunohistochemical staining. Percentage of positive nuclear staining was expressed as a strongly positive (SP) labeling index (LI). Before MPA treatment, SP LIs in the effective and noneffective groups were 22.6 +/- 14.3% and 9.1 +/- 9.2%. At 1-6 weeks in the MPA treatment, SP LIs increased in both groups and were significantly higher than those before the therapy. At 7-12 weeks, SP LIs in both groups decreased to the level of pretherapy. At 13-18 weeks, SP LIs in the effective group were 14.9 +/- 5.7%, whereas in the noneffective group, 1.1 +/- 2.0%. The former was significantly higher than the latter. p27 expression could predict the effectiveness of MPA treatment for endometrial carcinoma at an early stage of the 4-month period in MPA therapy and could be a useful predicting marker for MPA.

Adult↗

PubMedDate not supplied

Correlation between histological differentiation and DNA-synthesizing enzymes in rat colorectal tumors induced with 1, 2-dimethylhydrazine.

Thymidylate synthase and thymidine kinase are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis. Colorectal carcinogenesis induced with 1,2-dimethylhydrazine in rats enhanced mRNA expression levels of both enzymes, resulting in the increase of both enzyme activities and bromodeoxyuridine-immunoreactive S-phase cells. Poorly and well differentiated adenocarcinomas of the colorectum showed the relative elevation of activities of thymidylate synthase and thymidine kinase, respectively. These results indicate that the relationship between de novo and salvage pathways for pyrimidine nucleotide synthesis may depend on the histopathological grades of cell differentiation.

Animals↗

PubMedDate not supplied

Polysaccharides extracted from human tubercle bacilli (specific substance of Maruyama) reduces carcinogenesis in murine ulcerative colitis.

Polysaccharides extracted from human tubercle bacilli (specific substance of Maruyama) have been clinically applied in patients with malignant diseases in Japan and other countries. It is known that increased colorectal carcinogenesis occurs in patients with ulcerative colitis. The repeated mucosal necrosis-regeneration sequence in chronic ulcerative colitis induced with 3 % dextran sulfate sodium led to colorectal carcinogenesis in azoxymethane-pretreated mice. Simultaneously multiple injections with the polysaccharides reduced the increases in thymidylate synthase and thymidine kinase activities and a number of bromodeoxyuridine-incorporated S-phase cells in colorectal tissues resulted in the reduction of tumorous regions with high-grade dysplasia.

Animals↗

PubMedDate not supplied

Obliterative arteritis with nitric oxide synthase and HLA-DR expression in Crohn's colitis.

BACKGROUND/AIMS: To cast light on whether inflammatory vascular injury is a possible pathogenic mechanism in Crohn's disease, the histological characteristics of vascular lesions were investigated. METHODOLOGY: Affected vessels in surgically resected colons from 23 patients with Crohn's disease, 20 with ulcerative colitis, 7 with ischemic colitis, and 9 normal controls were analyzed by Victoria blue and hematoxylin and eosin staining as well as immunohistochemistry for HLA-DR, nitric oxid synthase, vascular endothelial growth factor and E-cadherin. RESULTS: Inflammatory-cell infiltrates affecting arteries, accompanied by obliterative intimal thickening, were more frequent in Crohn's disease cases than in the other groups (P < 0.05-0.0001). Crohn's disease activity was positively correlated with the degree of obliterative arteritis. Granulomatous vasculitis was found exclusively in Crohn's disease (10 cases; 43.5%). In addition, focally enhanced endothelial staining of HLA-DR, with expression in granulomas adjacent to vessels was occasionally observed. In the endothelium of affected vessels, strong expression of HLA-DR was more prevalent in Crohn's disease and/or ulcerative colitis as compared with the ischemic colitis and controls (P < 0.05-0.01). In the involved arteries, enhanced endothelial nitric oxide synthase expression was most common in Crohn's disease among the groups (P < 0.05). A few cases of Crohn's disease, ulcerative colitis and ischemic colitis were positive for inducible nitric oxide synthase, vascular endothelial growth factor or E-cadherin in the vessel walls. CONCLUSIONS: The presence of characteristic obliterative arteritis and granulomatous vasculitis, a possible cause of ischemic injury, supports, in part, a vascular hypothesis for the pathogenesis of Crohn's disease. Enhanced expression of endothelial nitric oxide synthase and HLA-DR possibly reflects compensatory endothelium-mediated vasodilation and amplification of the immune response, respectively.

Adult↗