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  • 1
    ISSN: 1573-7217
    Keywords: androgen receptor ; breast cancer ; mutation ; polymorphism ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prostate Specific Antigen (PSA) expression by breast epithelial cells is associated with favorable breast cancer prognosis. In preliminary studies, we found that a nucleotide variation (G → A) at position −158 in the androgen response element (ARE-1) of the PSA promoter was present in four out of 9 breast tumors examined and in a breast carcinoma cell line. We have now determined the nucleotide composition at position −158 of DNA extracted from 148 well-characterized breast tumors and compared tumor genotype with that of controls without cancer, with tumor PSA concentration and with clinicopathological variables, overall survival and disease free survival. The G → A base change at position −158 is a polymorphism. Allelotypes were similarly distributed in breast cancer patients and controls. The Mann–Whitney U Test showed a significantly higher tumor PSA concentration in tumors that presented a homozygous G as opposed to homozygous A genotype. Genotype at position −158 was not associated with clinicopathological variables in contingency table analysis. Univariate Cox regression models showed a 28% reduction in risk for death in patients with homozygous G genotype compared to those with homozygous A genotype (P=0.03). However, ARE-I genotype did not significantly add to the prognostic power in the multivariate model of overall survival. In summary, the base change at position −158 is a polymorphism that may affect breast cancer prognosis, but further studies are required to confirm this possibility and to investigate the relevance of this polymorphism in terms of breast cancer susceptibility.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7217
    Keywords: alleles ; Ha-ras ; oncogenes ; RFLP's
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The frequencies of 13 different Ha-ras proto-oncogene alleles have been estimated in 92 breast cancer patients and 60 unaffected individuals. The Ha-ras alleles can be identified using a DNA restriction fragment length polymorphism (RFLP) closely linked to the 3′ end of the gene, and are characterized by a different length due to a region of sequences repeated a variable number of times (variable tandem repeats, VTR). The statistical analysis of the data obtained shows that the frequency of alleles ranging between specific length limits is significantly higher in breast cancer patients than in controls. The same applies to specific genotypes bearing the aforementioned alleles. This suggests that the inheritance of these alleles may be associated with an increased risk of developing breast cancer.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7217
    Keywords: prostate specific antigen ; breast cancer ; fibroadenomas ; steroid hormones ; steroid hormone receptors ; benign breast disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prostate specific antigen (PSA) is a tumor marker used widely for the diagnosis and monitoring of prostatic adenocarcinoma. Recently, we provided evidence that PSA may also be produced by breast tumors. In this report we examined quantitatively the PSA levels in 199 breast tumors, 48 tissues with benign breast disease (BBD, 34 fibroadenomas), and 36 normal breast tissues. Significant amounts of PSA (≥ 0.030 ng of PSA per mg of total protein) were found in 28% of breast tumors, 65% of BBD tissues, and 33% of normal breast tissues. PSA positivity in breast tumors was highest in stage I disease (34%) and decreased with disease stage (24% in stage II and 18% in stage III–IV). Using polymerase chain reaction amplification we have shown PSA mRNA presence in patients with PSA protein-positive tissues (benign and malignant) but not in patients with PSA protein-negative tissues. Our data suggest that PSA is expressed frequently by normal breast tissue, by tissue of benign breast diseases, and by breast cancer tissue. Highest expression is seen in benign breast disease and lowest expression in advanced stage cancerous tissue. As PSA production is mediated by steroid hormones and their receptors, we propose that PSA may be a new marker of steroid hormone action in the normal or diseased female breast. The role of this enzyme in the development of breast diseases including breast cancer is currently unknown.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: breast cancer prognosis ; prognostic markers ; androgen receptor polymorphisms ; CAG repeats ; polyglutamine repeats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The androgen receptor (AR) is a transcription factor mediating the action of androgens. The AR gene is localized on chromosome X and it contains a series of CAG trinucleotide repeats. The length of the CAG repeats varies among individuals and this polymorphism is believed to be related to AR transcriptional activity. Studies have shown that fewer CAG repeats are associated with an increased risk as well as more aggressive forms of prostate cancer. Although AR is expressed in breast cancer and the impact of androgen and AR on breast cancer has been recognized, the role of the CAG repeats in breast cancer remains unknown. In this study, we measured the CAG repeats in breast cancer tissue using a PCR-based method. Of the 133 patients with primary breast cancer, 102 were heterozygous and 31 were homozygous. The mean CAG repeat number for homozygous women was 21; for heterozygous women the repeat number mean was 20 for the short allele and 24 for the long allele. The length of CAG repeats either in one allele or in both alleles was inversely correlated with the histological grade of breast cancer (r = −0.23 or −0.26, respectively, p〈0.05). An association between positive lymph nodes and fewer CAG repeats in both alleles was also suggested (p = 0.06). Furthermore, survival analysis indicated that the total number of CAG repeats in both alleles was associated with patient overall survival. With every CAG repeat increase, there was a 6% reduction in the risk of death (RR = 0.94, p = 0.03). The association remained significant after controlling for the homozygous and heterozygous status (RR = 0.92, p = 0.01). The association became no longer significant when clinical and pathological variables were adjusted in the analysis but this could be due to the reduction of sample size in the multivariate analysis. CAG heterozygosity and difference in number of CAG repeats between the two alleles were not associated with either disease features or patient survival. Our results suggest that longer CAG repeats may occur more frequently in less aggressive cancer and that the CAG repeats may play a role in breast cancer progression.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7217
    Keywords: breast cancer ; tumor-associated antigens ; monoclonal antibodies ; serum markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An enzyme-linked immuno-absorbent assay has been developed for the detection of a circulating tumorassociated antigen, 90K, recognized by murine monoclonal antibody SP-2 (Iacobelliet al., Cancer Res 46: 3005–3010, 1986). This assay was found to be simple and reproducible. Using this method, 6% of 165 apparently healthy individuals and 15% of 91 patients with benign breast disease showed 90K levels above 1.7 units/ml. Approximately 50% of 129 patients with advanced breast cancer demonstrated serum antigen levels above 1.7 units/ml. All histological types of breast cancer were positive, and no association between the incidence of elevated 90K levels and other prognostic variables could be detected. The titers of 90K were significantly higher in sera from advanced-stage (3 and 4) patients than in those from patients with limited-stage (1 and 2) disease. Elevated 90K levels were also observed in patients with carcinomas of other sites, including gastrointestinal, gynecological, and lung tumors. By means of the immune blotting technique, the antigenic components carrying the determinants in serum and extracts of breast cancer cells have been identified. The levels of 90K did not correlate with those of CA 15-3 or CEA. The measurement of 90K in sera appears to be a useful adjunct to other available assays for the detection and monitoring of breast cancer and other malignant tumors.
    Type of Medium: Electronic Resource
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