PubMed Health⌕ Search

Biomedical subjects

Monique A Spillman

Publications and source records attributed to Monique A Spillman.

6 recordsLinked to original sources
PubMed2006

Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in epithelial ovarian cancer.

Overexpression of the imprinted insulin-like growth factor-II (IGF2) is a prominent characteristic of gynecologic malignancies. The purpose of this study was to determine whether IGF2 loss of imprinting (LOI), aberrant H19 expression, and/or epigenetic deregulation of the IGF2/H19 imprinted domain contributes to elevated IGF2 expression in serous epithelial ovarian tumors. IGF2 LOI was observed in 5 of 23 informative serous epithelial ovarian cancers, but this did not correlate with elevated expression of IGF2 H19 RNA expression levels were also found not to correlate with IGF2 transcript levels. However, we identified positive correlations between elevated IGF2 expression and hypermethylation of CCCTC transcription factor binding sites 1 and 6 at the H19 proximal imprint center (P = 0.05 and 0.02, respectively). Hypermethylation of CCCTC transcription factor sites 1 and 6 was observed more frequently in cancer DNA compared with lymphocyte DNA obtained from women without malignancy (P < 0.0001 for both sites 1 and 6). Ovarian cancers were also more likely to exhibit maternal allele-specific hypomethylation upstream of the imprinted IGF2 promoters when compared with normal lymphocyte DNA (P = 0.004). This is the same region shown previously to be hypomethylated in colon cancers with IGF2 LOI, but this was not associated with LOI in ovarian cancers. Elevated IGF2 expression is a frequent event in serous ovarian cancer and this occurs in the absence of IGF2 LOI. These data indicate that the epigenetic changes observed in these cancers at the imprint center may contribute to IGF2 overexpression in a novel mechanistic manner.

Alleles↗
PubMed2005

Transforming growth factor beta receptor I polyalanine repeat polymorphism does not increase ovarian cancer risk.

OBJECTIVES: It has been suggested that the 6A allele of the type I TGFbeta receptor (TGFbetaR1) polyalanine repeat tract polymorphism may increase susceptibility to various types of cancer including ovarian cancer. METHODS: The TGFbetaR1 polyalanine polymorphism was genotyped in 588 ovarian cancer cases and 614 controls from a population-based case-control study in North Carolina. RESULTS: Significant racial differences in the frequency of the 6A allele were observed between Caucasian (10.7%) and African-American (2.4%) controls (P < 0.001). One or two copies of the 6A allele of the TGFbetaR1 polyalanine polymorphism was carried by 18% of all controls and 19% of cases, and there was no association with ovarian cancer risk (OR = 1.07, 95% CI 0.80-1.44). The odds ratio for 6A homozygotes was 1.81 (95% CI 0.655.06), but these comprised only 0.98% of controls and 1.70% of cases. CONCLUSIONS: The 6A allele of the TGFbetaR1 polyalanine polymorphism does not appear to increase ovarian cancer risk. Larger studies would be needed to exclude the possibility that the small fraction of individuals who are 6A homozygotes have an increased risk of ovarian or other cancers.

Adult↗
PubMed2004

Managing familial risk in genetic testing.

Increasing numbers of people are seeking genetic testing and uncovering information that directly concerns their biological relatives as well as themselves. This familial quality of genetic information raises ethical quandaries for physicians, particularly related to their duty of confidentiality. In this article, the American Medical Association's Council on Ethical and Judicial Affairs examines the informed consent process in the specific context of genetic testing, giving particular consideration to the handling of information that has consequences for biological relatives. Furthermore, it addresses the question of whether physicians' obligation to warn biological relatives ever should override the obligation to protect patient confidentiality.

Family Health↗
PubMed2002

Managing conflicts of interest in the conduct of clinical trials.

The interaction between medical research and for-profit corporations is not new, but it has expanded considerably in recent years. Some of the recent trends may accelerate the research process, particularly when large clinical trials are required. However, a renewed commitment to the application of high ethical standards is essential to ensure that societal trust in research is not eroded, subjects enrolled in trials do not become merely a means to an end, and medical research is efficiently translated into clinical advances that will benefit future patients. This article focuses on the analysis of conflicts of interest in the conduct of clinical trials in both academic and community-based settings. Specifically, it discusses how the roles of research scientists and clinical practitioners differ and the importance of ensuring that participants' consent to enroll in clinical trials is not the result of confusion about the goals of an experimental treatment that may resemble clinical care. The article also discusses the potential conflicts of interest that can arise when clinicians stand to gain from enrolling their own patients as subjects in clinical trials and examines various instances in which disclosure of information regarding funding and compensation may serve to minimize such conflicts. This article emphasizes that to preserve the integrity of research and to protect the welfare of human subjects who enroll in trials, physicians should have adequate training in the conduct of research and be familiar with the ethics of research. When a physician has treated or continues to treat a patient who is eligible to enroll as a subject in a clinical trial conducted by the same physician, someone other than the treating physician should obtain the participant's informed consent. Finally, the article addresses disclosure of financial incentives and related funding issues.

Biomedical Research↗