Showing papers by "John I. Risinger published in 2007"

Racial disparities in blacks with gynecologic cancers

Abstract: Black women have a lower incidence of gynecologic cancers but they have a higher mortality associated with their disease. The etiology of the racial disparity in outcome among gynecologic cancer patients is multifactoral and site-specific. Black women with endometrial cancer often present with more advanced stage tumors that are associated with a worse prognosis compared with White women. Evidence suggests that observed disparities in outcome are due to inequalities in treatment or differing biologic etiologies. For cervix cancer, studies have suggested that survival among Black women may be lower than survival among White women that develop this disease. This occurs despite evidence that indicates that Pap smears are utilized similarly by Black and White women for cervix cancer screening. These differences in outcome may become less pronounced when comorbidities are accounted for and inequalities in treatment are eliminated. For ovarian cancer patients, survival has improved with the use of contemporary therapies over the past 30 years in Whites but less so for Blacks. This may be due to differences in the likelihood of primary surgical cytoreductions, which are performed less frequently in some Black women because of extensive metastatic spread or comorbidities. The observed decreases in survival for all 3 gynecologic cancers potentially may be affected by socioeconomic status of the patient in some healthcare settings. An improved understanding of the causative factors associated with racial disparities in gynecologic cancer outcome is necessary to facilitate efforts aimed at correcting this important healthcare problem.

Global Expression Analysis of Cancer/Testis Genes in Uterine Cancers Reveals a High Incidence of BORIS Expression

Abstract: Purpose: Cancer/testis (CT) genes predominantly expressed in the testis (germ cells) and generally not in other normal tissues are aberrantly expressed in human cancers. This highly restricted expression provides a unique opportunity to use these CTgenes for diagnostics, immu- notherapeutic, or other targeted therapies. The purpose of this study was to identify those CT genes with the greatest incidence of expression in uterine cancers. Experimental Design: We queried the expression of known and putative CT gene transcripts (representing 79 gene loci) using whole genome gene expression arrays. Specifically, the global gene expressions of uterine cancers (n = 122) and normal uteri (n = 10) were determined using expression data from the Affymetrix HG-U133A and HG-U133B chips. Additionally, we also examined the brother of the regulator of imprinted sites (BORIS ) transcript by reverse transcrip- tion-PCR and quantitative PCR because its transcript was not represented on the array. Results: Global microarray analysis detected many CT genes expressed in various uterine cancers; however, no individual CT gene was expressed in more than 25% of all cancers. The expression of the two most commonly expressed CT genes on the arrays, MAGEA9 (24 of 122 cancers and 0o f 10 normal tissues) andDown syndrome critical region 8 (DSCR8)/MMA1 (16 if 122 cancers and 0 of 10 normal tissues), was confirmed by reverse transcription-PCR methods, validating the array screening approach. In contrast to the relatively low incidence of expression of the other CTgenes, BORIS expression was detected in 73 of 95 (77%) endometrial cancers and 24 of 31 (77%) uterine mixed mesodermal tumors. Conclusions: These data provide the first extensive survey of multiple CT genes in uterine cancers. Importantly, we detected a high frequency of BORIS expression in uterine cancers, suggesting its potential as an immunologic or diagnostic target for these cancers. Given the high incidence of BORIS expression and its possible regulatory role, an examination of BORIS function in the etiology of these cancers is warranted.

Evolutionary diversification of SPANX-N sperm protein gene structure and expression.

Abstract: The sperm protein associated with nucleus in the X chromosome (SPANX) genes cluster at Xq27 in two subfamilies, SPANX-A/D and SPANX-N. SPANX-A/D is specific for hominoids and is fairly well characterized. The SPANX-N gave rise to SPANX-A/D in the hominoid lineage approximately 7 MYA. Given the proposed role of SPANX genes in spermatogenesis, we have extended studies to SPANX-N gene evolution, variation, regulation of expression, and intra-sperm localization. By immunofluorescence analysis, SPANX-N proteins are localized in post-meiotic spermatids exclusively, like SPANX-A/D. But in contrast to SPANX-A/D, SPANX-N are found in all ejaculated spermatozoa rather than only in a subpopulation, are localized in the acrosome rather than in the nuclear envelope, and are expressed at a low level in several nongametogenic adult tissues as well as many cancers. Presence of a binding site for CTCF and its testis-specific paralogue BORIS in the SPANX promoters suggests, by analogy to MAGE-A1 and NY-ESO-1, that their activation in spermatogenesis is mediated by the programmed replacement of CTCF by BORIS. Based on the relative density of CpG, the more extended expression of SPANX-N compared to SPANX-A/D in nongametogenic tissues is likely attributed to differences in promoter methylation. Our findings suggest that the recent duplication of SPANX genes in hominoids was accompanied by different localization of SPANX-N proteins in post-meiotic sperm and additional expression in several nongonadal tissues. This suggests a corresponding functional diversification of SPANX gene families in hominoids. SPANX proteins thus provide unique targets to investigate their roles in the function of spermatozoa, selected malignancies, and for SPANX-N, in other tissues as well.