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Category : Electronic books
Languages : en
Pages : 87
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Globally, prostate cancer is the most common invasive malignancy and the sixth leading cause of cancer-related death in men. Prostate cancer incidence is significantly higher in the United States compared to most other countries, due to dietary and environmental factors. Well-established risk factors for prostate cancer include increasing age, African ancestry, and a family history of prostate cancer1. African Americans have a higher incidence at a younger age, more aggressive forms of the disease, and shortest survival for all major cancers, and disparities persist despite an improved understanding of early detection, genetics, and socioeconomic risk factors1. Ethnicity/race is the major risk factor, after adjusting for age in this type of cancer. In prostate cancer, the tumor microenvironment (stroma) is considered to be a niche which favors tumor cell proliferation, survival, invasion, and metastasis2. Interaction with cancer cells can lead to genetic changes in stroma cells. Active stromal components mostly contain smooth muscle cells, fibroblasts, vascular endothelial cells, carcinoma-associated fibroblasts, and inflammatory cells3. Cancer-associated fibroblasts are functionally and structurally different from fibroblasts, which exist adjacent to the normal epithelium. These cells, when mixed with normal prostate epithelial cells, can induce their malignant transformation4. Microarray analyses have identified pathways that are significantly associated with tumor and stromal tissues in prostate cancer5. 20% of these pathways are extracellular matrix components, cell adhesion molecules, and epithelial to mesenchymal transition5. In addition previous studies analyzing microarray data showed significantly modified gene expression between African American and Caucasian American stromal tissue6. Tissue microarrays are a useful technique for profiling protein expression in a large number of samples and is applied in this thesis project for the purpose of the microarray results optimization, validation, and its racial disparity outcomes in prostate cancer, as well as to determine if products of differentially expressed genes in tumor versus stroma of prostate cancer tissues follow the same pattern as transcript levels. We were going to quantify the proteins of interest using immunohistochemistry in an independent cohort of African American and Caucasian American prostate cancer samples.
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Category : Electronic books
Languages : en
Pages : 60
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An alarming disparity still exists in many cancer types, particularly in prostate cancer (PCa), in spite of new cancer therapeutics and substantial improvements in disease diagnostics. African American men have the highest mortality rates in PCa when compared to men of other races. These substantial differences in mortality are attributed to factors that include socioeconomic status, access to healthcare, family history, and biology. Evidence for the immune system’s critical role in cancer has encouraged the development of immunotherapies for cancer treatment. These therapies serve to enhance the immune system’s recognition of malignant tissues to inhibit cancer progression. Although current immunotherapies have significant impact on the immune response to cancer, many of the immune mechanisms in cancer have yet to be characterized. The immune response in PCa, as well as other cancer types, is critical for inhibiting the growth and progression of tumors. Effective anti-tumor immunity is characterized by high prevalence of cytotoxic T lymphocytes (CTLs) in the tumor microenvironment. CTLs have the ability to directly destroy malignant cells, making them crucial for inhibiting tumor development. The prevalence of CTLs within tumor tissues is associated with improved clinical outcomes in colon, breast, and ovarian cancers. Strong adaptive anti-tumor responses involve effective antigen presentation for the efficient activation of immune cells that contribute to high CTL activity. Our work focuses on identifying differences in expression of specific anti-tumor immune markers between African Americans (AA) and Caucasian Americans (CA) to pinpoint the immune mechanisms that contribute to the racial disparities in PCa. Our immunohistochemical studies indicate differences by race in two major aspects of anti-tumor immunity: antigen presentation by tumors and lymphocyte recruitment to tumor tissues. Previous studies from our lab have revealed significant differences in gene expression of various immune markers by race. HLA-DMB and HLA-DPA1, two genes important in antigen presentation, are higher expressed in tumors of CA compared to those of AA. Both immune products are expressed by various tumor types and antigen presenting cells (APCs). CA tumors also had greater numbers of CD8+ cells, which may potentially be cytotoxic. Collectively, these data indicate greater anti-tumor immunity in CA patients.
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Category :
Languages : en
Pages : 0
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We used RDA to identify homozygously deleted DNA clones within metastatic prostate cancer xenograft DNA, and found that all of the homozygously deleted clones mapped to a single region of chromosome 12p. We confirmed that the metastatic lesions from this patient also contained this homozygous deletion, and then analyzed this region in a series of 41 metastatic tumors from 19 patients, where we found that 50% of patients' tumors show loss. This 12p deletion occurs with similar frequency in caucasians and african-americans based on our small sample. We mapped this genomic region, and found that two previously identified potential candidate genes ETV(tel) and CDKN1B(p27) are located there. Analysis of these genes has revealed no sequence changes consistent with an important tumor suppressor role. Extensive analysis of p27 for possible mutational or methylation changes was negative. Major observations from our work include the finding of a homozygous deletion on chromosome 12p in metastatic prostate cancer, considered to be a major indicator that an important gene is nearby on chromosome 12p. Further analysis of this region revealed unexpected high degree of allelic loss in this region. Specific genes in the region were analyzed, and p27 appears to be the likely target, inactivated by loss of one copy. Further analysis was curtailed due to lack of funding.
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Category :
Languages : en
Pages : 9
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This critical hypothesis development project is still underway and we have requested a deadline extension without additional funding to allow us to complete the work. The two sources of the delay are 1) histological analysis of all tissues available for study took longer than expected but is now complete and 2) we have been working (using other sources of funding) to get a lab database ready to handle the data in way that will allow the data generated to be optimally useful for prostate cancer research. This work has taken longer than expected but is nearly ready. In order to complete the project as soon as possible and to extend its utility our laboratory has entered into a collaboration with another laboratory and our goal is have a manuscript ready by Fall 2006.
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Languages : en
Pages : 13
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Vitamin A (retinol) and its related metabolites like retinoic acid (RA) have great potential in their roles as prostate cancer chemopreventive and chemotherapeutic agents by exerting regulation on cell growth and differentiation. Several studies have shown that there is a reduction in retinoid levels and retinoid receptors (e.g. RARBeta2) in prostate cancer. RA is being used to treat patients with prostate cancer and has been shown to inhibit tumor growth and reverse the events of carcinogenesis in animal models of prostate cancer. There is a disparity in prostate cancer among the African-American population and we hypothesize that more severe disruptions of retinoid signaling occur, contributing to this disparity. The purpose of this study is to examine the underlying causes for the clinical behavior of prostate cancer in African-Americans as compared to Caucasian patients. Immunohistochemical analysis has shown the expression of LRAT, an enzyme responsible for retinol esterification and storage as retinyl esters, to be reduced in tumor tissue specimens from prostate cancer patients as compared to adjacent nonmalignant tissue. Understanding the role of retinoid signaling in prostate carcinogenesis will lead to improved chemoprevention strategies and to the development of novel therapies for this disease.
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Languages : en
Pages : 0
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Significant progress has been made for all three specific aims. Specific Aim 1: Obtaining metastatic prostate cancer DNA of quality sufficient for Representational Difference Analysis (RDA), has been achieved using alternate means. Specific Aim 2: Employ RDA to identify DNA regions which have been homozygously deleted, has been achieved with identification of a novel region of homozygous deletion on chromosome 12p (Cancer Research, 58, 5652-5655, 1998). Specific Aim 3: To prioritize regions of homozygous deletion based on frequency of deletion of this region in metastatic tumors, and to identify candidate genes within these regions, has been achieved, with previously unidentified deletion of the identified chromosome 12p region in 50% of metastatic prostate cancers studied (Genes, Chromosomes, and Cancer 25:270-276, 1999) . Examination of genes within this region suggests that p27 or TEL to be likely candidates. These results validate this approach and additional studies are underway to identify additional genomic regions of interest in metastatic prostate cancer.
Author: Nikelia QuaTrail Judenary
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ISBN:
Category : African American men
Languages : en
Pages : 100
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Category :
Languages : en
Pages : 12
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Prostate Cancer is the most common cancer among African American males. Recent reports suggest that not only is the incidence higher than their white counterparts, but that they present at an earlier age with more diffuse disease, and have a higher morbidity and mortality. Our current study is designed to evaluate potential differences in tumor suppressor genes between cancers of non-Hispanic Whites and African Americans. We have selected the tumor suppressor genes BCL-2, p53 and Rb. We have selected cancers from America as well as South Africa to assess the potential for an increased virulence in African Americans compared to whites and Native Africans. In this initial grant we are funded to establish a laboratory and to prepare to write a Department of Defense grant that was submitted in the spring of 1999.
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Category :
Languages : en
Pages : 6
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African American men have the highest incidence and mortality from prostate cancer in the world. Multiple reasons have been postulated to explain these findings, although the definitive reasons for them are unknown. While both environmental and genetic factors may contribute to prostate cancer susceptibility, results from multiple studies consistently implicate a strong genetic component to this cancer. However, a specific gene that is consistently and reproducibly associated with prostate cancer risk in any population has not been identified. Association studies examining the frequency of common but specific genetic variants in study populations with and without a particular disease (i.e., case-control) is a powerful way to detect the influence of common genetic variants capable of affecting disease risk. While these types of studies are powerful, they are not without limitations, including the tendency to be confounded due to population stratification (a critical issue in admixed populations like African Americans), and the requirement for large, well-matched, and well-characterized study populations. While there has been extensive use of case control studies to identify genetic risk variants in Caucasian populations, corresponding studies in the African American prostate cancer population have been less extensive, typically being much smaller than their Caucasian counterparts, with little or no effort to address the critical issue of population stratification as a confounder. It is now quite clear that unless cases are well matched to controls in terms of genetic heterogeneity in such studies, spurious associations will and undoubtedly have been observed and reported. In this study, the author uses Ancestry Informative Markers (AIM) to match African American prostate cancer cases and controls for the purposes of performing association studies without confounding by population stratification.
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Category :
Languages : en
Pages : 22
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In the first hypothesis, CYP1B1 expression in Caucasian prostate cell lines were increased in cancerous (DU145 & PC-3) compared to normal (RWPE-1) cells. Analysis of expression in human tissue cDNAs from Caucasians also showed higher levels of CYP1B1 in cancer compared to BPH. CYP1B1 protein was present in both races and though not significant, generally was higher in tumor regions compared to normal adjacent regions for both African-Americans and Whites. In the second hypothesis, racial differences for CYP1B1 polymorphisms are observed as allele frequencies for the variant at codons 119 and 432 are greater among Blacks (P0.001) whereas the 453 variant is predominant in Whites (P0.001). Within race, a case control study show the variant at codon 453 plays a protective role for PC among Blacks (P
