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A trial to establish whether laser treatment of anal precancer prevents development of anal cancer in HIV-positive men who have sex with men

ABSTRACT: Background and study aims Anal cancer is a growing problem in the UK. Almost 90% of these cancers are caused by the human papillomavirus (HPV). HPV infection in a weakened immune system can lead to abnormal cell changes which are graded as anal intraepithelial neoplasia (AIN) 1-3, with AIN 2 and AIN 3 considered to be high-grade neoplasia (AIN 2/3). These changes are called precancers, but it is not known how many, over what time period will turn to cancer. Although many doctors and scientists think we need to treat AIN 2/3 (precancer), as is done in women for cervical precancer to prevent cancer, there is no proven treatment for anal precancer (AIN 2/3) that will prevent anal cancer. Laser treatment may be an effective strategy to prevent anal cancer. The main aim of the study is to assess the long-term effect (up to 5 years) of laser treatment in preventing anal cancer in HIV-positive men who have sex with men with anal precancer. Who can participate? HIV-positive men who have sex with men, who have anal precancer What does the study involve? Participants are randomly allocated to one of two groups. Participants in the treatment group undergo laser ablation of their perianal (external) or anal canal (internal) disease under local anaesthetic injections. If the disease volume (extent) is large the ablation may be done under general anaesthetic as a day case. Rarely, it may be necessary to treat extensive disease as a staged procedure over more than one treatment visit. Participants in the active surveillance group receive no treatment. All participants are followed up every 6 months with standard examinations. The number of cancers, the effect of treatment on preventing new precancer, quality of life, and the costs of treatment are compared between the groups.

DISEASE(S): Anus,Colorectal Cancer

PROVIDER: 2410507 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Context: Although androgen treatment increases muscle mass in HIV-infected men, the underlying mechanisms are poorly understood. Analysis of genome-wide microarray data obtained from skeletal muscle biopsies can be used to profile androgen-regulated pathways. Objective: To identify genes and pathways associated with testosterone treatment and myogenesis in the context of HIV-infected men using genome-wide microarray analysis of skeletal muscle biopsies. Results: A significant weight gain was observed in subjects treated with testosterone compared to placebo (+2.05 kgs and â??1.07 kgs, respectively; P = 0.003) as well as gains in DEXA lean; mass (2.93 kgs vs. 0.35 kgs, respectively; P = 0.003). Microarray expression profiles and RTPCR validation of RNA after 14 days of treatment indicated that several gene sets including; transcriptional control, myogenesis, adipogenesis, insulin signaling, apoptosis, cell cycle, chromatin remodeling, and stress response genes were differentially expressed with testosterone treatment. Protein expression analysis of myogenic differentiation and protein synthesis markers (MyoD, Myogenin, phosphorylated p38 MAPK and phosphorylated AKT) in muscle biopsies and skeletal muscle cells treated with DHT confirmed that testosterone engages; a network of pro-myogenic genes. Conclusions: Testosterone-associated gain in muscle mass in HIV-infected men engaged a network of regulatory pathways involved in broad transcriptional control, myogenesis, insulin signaling, chromatin remodeling, and stress response. Further evaluation of precise signaling intermediates within androgen regulated pathways may help to better define improvements in muscle mass, both in healthy and HIV infected patients. Experiment Overall Design: Design, Setting, and Participants: 44 HIV+ men with weight loss were randomized to receive either 300mg testosterone enanthate or placebo injections IM weekly for 16 weeks. Muscle Experiment Overall Design: biopsies were obtained at baseline and on treatment day 14. A random subset of specimens was chosen for microarray analysis; changes in selected genes were confirmed by reverse transcriptase - polymerase chain reaction (RT-PCR), and western blot analysis. Human skeletal Experiment Overall Design: myogenic precursor cells (SkMCs) were cultured in vitro in the presence of dihydrotestosterone (DHT) to evaluate activation of myogenic protein expression. Experiment Overall Design: Main outcome measures: Relative RNA levels in skeletal muscle biopsies were measured by expression profiling with microarrays and expression levels were validated in samples using quantitative RT-PCR. Further confirmation of changes in key myogenic biomarkers was obtained in DHT treated SkMCs.

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A trial to establish whether laser treatment of anal precancer prevents development of anal cancer in HIV-positive men who have sex with men

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