Objectives To assess the impact of HAART use on AIDS-defining KS and NHL among adults with AIDS. Design Registry linkage study. Methods Adults diagnosed with AIDS from 1990 to 2000 in the San Francisco AIDS case registry were matched with cancer cases diagnosed from 1985 to 2002 in the California Cancer Registry. Multivariate Cox proportional hazards models were used to evaluate the risk and survival of AIDS- related KS, systemic NHL, and primary CNS lymphoma. Results Of the 14,183 adults with AIDS, 3028 were diagnosed with KS, 776 with systemic NHL, and 254 with CNS NHL. After adjustment for potential confounders, more recent calendar period and use of HAART were significantly associated with a decreased risk of KS while HAART use but not calendar period were significantly associated with systemic and CNS NHL. In adjusted analysis of KS survival time, there was strong evidence of a reduced risk of death associated with HAART use and more recent calendar period. In contrast, in adjusted analyses of systemic NHL survival time, HAART use was not associated with improved survival time; however, calendar period was associated with longer survival. In adjusted analysis of CNS NHL survival time, only cancer treatment was associated with a longer survival time. Conclusions After controlling for calendar period and other confounders, use of HAART decreased the risk of KS, systemic NHL, and CNS NHL. Use of HAART also increased KS survival time but not NHL survival time.

Progesterone and its receptor, PR, are essential for uterine leiomyoma (LM, a.k.a., fibroid) tumorigenesis, but the underlying cellular and molecular mechanisms remain unclear. The receptor activator of NF-κB (RANKL) was recently identified as a novel progesterone/PR-responsive gene that plays an important role in promoting LM growth. Here, we used RANKL as a representative gene to investigate how steroid hormone, genetic, and epigenetic signals are integrated to regulate LM stem cell (LSC) function. We demonstrated that RANKL specifically upregulates LSC proliferation through activation of Cyclin D1. RANKL gene transcription was robustly induced by the progesterone agonist R5020, leading to a dramatically higher RANKL expression in LM compared to adjacent myometrial (MM) tissue. MethylCap-Seq revealed a differentially methylated region (DMR) adjacent to the distal PR-binding site (PRBS) 87 kb upstream of the RANKL transcription start site. Hypermethylation of the DMR inhibited recruitment of PR to the adjacent PRBS. Luciferase assays indicated that the DMR and distal PRBS constitute a novel RANKL distal regulatory element that actively regulates RANKL expression. Furthermore, MED12 physically interacts with PR in LM tissue. The interaction between MED12 and PR, binding of PR and MED12 to PRBS, and RANKL gene expression are significantly higher in LM containing a distinct MED12 mutation (G44D) than in LM with wild-type MED12. In summary, our findings suggest that DNA methylation and MED12 mutation together constitute a complex regulatory network that affects progesterone/PR-mediated RANKL gene expression, with an important role in activating stem cell proliferation and fibroid tumor development.

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Objective To determine racial/ethnic differences in treatment experiences and expectations among women with fibroids. Methods Sixty women with symptomatic uterine fibroids completed semi-structured interviews, demographic surveys and a health literacy assessment. Participants were recruited from community-based organizations and health care organizations. Data from interviews were analyzed using a grounded theory approach. Three coders identified major themes and subthemes. Results The kappa (κ) amongst coders was 0.94. The mean age of participants was 43.0 ± 6.8 (mean ± SD). 61.7% of subjects were African-American (AAW), 25.0% were Non-Hispanic White (WW), 8.3% were Hispanic (HW) and 5.0% were Asian (ASW). When considering treatment options, AAW were more likely to want a permanent intervention. They were also more likely to demonstrate an aversion toward conventional treatments. Of the women who received a surgical intervention, AAW were also more likely to have had a difficult recovery and to be dissatisfied with their treatment. Finally, AAW disproportionately expressed concern regarding financial challenges. Conclusions AAW have high treatment expectations, have more financial obstacles, and are less satisfied with their treatment outcomes than women of other racial/ethnic groups. Our findings suggest a need to create targeted patient interventions and education to ameliorate these disparities in experience.

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