Biomedical subjects

Takeo Sakurai

Publications and source records attributed to Takeo Sakurai.

25 records · Page 2Linked to original sources

PubMedDate not supplied

Correlation of prostate-specific antigen promoter polymorphisms with clinicopathological characteristics in breast cancer.

We have identified two novel polymorphisms in the prostate-specific antigen (PSA) gene promoter regions, the A-AA allele and G-A allele. Furthermore, we have found that A-AA occurred frequently in tumors with higher PSA expressions. We hypothesize that allelic differences may be associated with different phenotypes of breast cancer. To test this hypothesis, we assayed the PSA genotype for 101 breast cancer cases. We also performed immunostaining analysis for estrogen receptor, p53, MIB-1 and c-erbB-2 on all the tumors. At the time of diagnosis, the A-AA allele occurred more frequently in the tumors characterized by small tumor size, good to moderate differentiation, p53-negativity and low tumor proliferation activity. Our results suggest that the presence of the A-AA allele at the PSA promoter region is associated with less aggressive forms of breast cancer and could be looked on as a favorable prognostic factor.

Alleles↗

PubMedDate not supplied

Thymidine phosphorylase and breast carcinoma.

Thymidine phosphorylase (TP), also known as platelet-derived endothelial-cell growth factor (PD-ECGF), is an enzyme that catalyzes the reversible dephosphorylation of thymidine, deoxyguridine and their analogs. TP also has angiogenic properties, although the precise mechanism by which it promotes angiogenesis is not known. TP expression is elevated in many solid tumors including ductal carcinoma in situ and invasive carcinoma of the breast. This has led to intensive study to ascertain whether TP is a biological marker in breast carcinoma; however, the clinical work has produced conflicting results. Some studies have suggested that TP is angiogenic in breast carcinoma, however, we and others have found that TP has little effect on tumor angiogenesis of invasive breast carcinoma. However, increasingly clinical results suggest that TP could represent an interesting marker that could respond to pyrimidine analogues. Widespread application of TP in prognostic testing would require greater uniformity in scoring techniques and determination of the cut-off levels which could distinguish individuals at high and low risk of cancer recurrence and death.

Breast Neoplasms↗

PubMedDate not supplied

BRCA1 in non-inherited breast carcinomas (Review).

Breast cancer occurs in hereditary and sporadic form. Breast cancer susceptibility gene (BRCA1) is known to be responsible for hereditary breast cancer. BRCA1 mutations are rare in sporadic cancers, but loss of BRCA1 resulting from reduced expression or incorrect subcellular localization is postulated to be important in non-familial breast cancers. More than 300 germline mutations have been identified so far in patients with familial breast and/or ovarian cancer, however, only a few somatic mutations have been identified in sporadic breast cancer. The decreased expression of BRCA1 in sporadic breast cancer is thought to be caused by other mechanisms, such as CpG methylation. BRCA1 expression may play an important role in the pathogenesis and prognosis of sporadic breast carcinoma.

Aged↗

PubMedDate not supplied

Prognostic value of Bcl-2 in invasive breast cancer receiving chemotherapy and endocrine therapy.

Apoptosis induced by anticancer agents is a mechanism of treatment activity, overexpression of antiapoptotic genes could produce drug resistant tumors. We have demonstrated that the susceptibility of Bcl-2-negative tumors to a series of anticancer drugs was significantly higher than that of Bcl-2-positive tumors. The purpose of this study was to examine if negative Bcl-2 expression has treatment benefit in breast cancer patients received chemotherapy and endocrine treatment. A cohort of 147 Japanese women with invasive ductal carcinoma was studied. All the patients received postoperative adjuvant therapy consisting of combination chemotherapy with cyclophosphamide, epirubicin, and fluorouracil, and tamoxifen therapy. The expression of Bcl-2, estrogen receptor (ER) and MIB-1 was evaluated in breast cancer surgical specimens. Bcl-2 immunostaining was inversely correlated with increasing histologic grade (p=0.0095) and MIB-1 (p=0.0128). Furthermore, a positive correlation between Bcl-2 and ER was observed (p<0.0001). Unexpectedly, survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that Bcl-2-positivity was associated with favorable prognosis (p=0.0430). Cox proportional hazard model demonstrated that positive Bcl-2 expression still has favorable survival (p=0.0242) after consideration of other prognostic factors. Our results imply that Bcl-2 is a significant favorable prognostic factor for breast cancer with chemotherapy and endocrine therapy.

Adult↗

PubMedDate not supplied

Loss of Msh2 is not associated with FHIT deletion in breast carcinomas.

The FHIT gene is a candidate tumor suppressor gene that has been implicated in the development and progression of breast carcinoma. Recent studies have suggested that Fhit inactivation can be a consequence of defects in mismatch repair proteins, particularly Msh2. Fifty-three breast carcinomas were evaluated for Fhit and Msh2 expression by immunohistochemical staining. The same breast carcinomas were examined for allelic loss at three loci within or near FHIT by PCR-based microsatellite analysis. Seventeen of the 53 breast cancer cases were positive for Fhit protein, and 10 of the 43 informative cases showed FHIT loci deletion. Twenty-five of the 53 (47%) cases showed loss of Msh2 expression. No relationship between Msh2 protein loss and FHIT locus alteration or Fhit protein loss could be observed. Our results suggest that this mismatch repair protein may play little role in maintaining the integrity of the common fragile locus with the FHIT gene.

Acid Anhydride Hydrolases↗

PubMedDate not supplied

5-aza-2'-deoxycytidine induces retinoic acid receptor beta 2 demethylation, cell cycle arrest and growth inhibition in breast carcinoma cells.

Like all cancers, breast cancer is considered to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumor suppressor loss. More recently, CpG island hypermethylation is known to be associated with gene silencing in cancer, and these silenced genes can be reactivated by 5-aza-2'-deoxycytidine (5-Aza-CdR). Retionoic acid receptor beta 2 gene is a tumor suppressor gene and the chemopreventive effects of retinoids are due to induction of RAR beta 2. In this study, the effect of 5-Aza-CdR RAR beta 2 restoration was investigated in the MRK-nu-1 human female breast cancer cell line. Changes of the RAR beta 2 methylation status were assessed by methylation-specific PCR. Reverse transcription PCR was used to evaluate RARb beta 2 restoration. Cell cycling and growth inhibition were studied using flow cytometric analysis of DNA content and CellTiter 96 AQueous non-radioactive cell proliferation assay, respectively. 5-Aza-CdR treatment resulted in complete demethylation of the RAR beta 2 gene. RAR beta 2 restoration was accompanied by cell cycle arrest (increase in the G0/G1- and decrease in the S- and G2/M-phases) and time-dependent growth inhibition. In conclusion, RAR beta 2 can be activated in vitro by 5-Aza-CdR, which may be one of the mechanisms for the tumor cell growth inhibition by 5-Aza-CdR.

Antimetabolites, Antineoplastic↗

PubMedDate not supplied

Correlation between BRCA1 expression and apoptosis-related biological parameters in sporadic breast carcinomas.

BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian cancer syndrome. Increased evidence suggests that BRCA1 protein is involved in mammary carcinogenesis in sporadic and hereditary forms. Recent experimental results suggest that BRCA1 plays a role in the regulation of apoptosis. In order to test whether the analysis of human tumors would provide data supporting this hypothesis in sporadic breast carcinomas, we have investigated the relationship between BRCA1 and apoptosis-related genes. Immunohistochemical analysis was performed to determine BRCA1 and the apoptosis-related proteins bcl-2, Bax and p53 in paraffin-embedded tissues of 156 sporadic invasive ductal carcinomas. BRCA1 expression was positively-correlated with Bcl-2 expression (p = 0.0008), but no relationship between BRCA1 expression and Bax or p53 expression could be established. In addition, loss of BRCA1 expression was also related to poor tumor differentiation and lymph node metastasis. Our study shows that bcl-2 might be one of the target genes involved in the oncogenesis related to BRCA1. Loss of BRCA1 may contribute to tumor development in breast carcinomas, which may be independent of the p53 tumor suppressor.

Apoptosis↗