Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To make feasible future clinical trials with new-generation human papillomavirus (HPV) vaccines, novel virological surrogate endpoints of progressive disease have been proposed, including high-risk HPV (HR-HPV) persistence for six months (6M+) or 12 months (12M+). The risk estimates (relative risks [RRs]) of these 'virological endpoints' are influenced by several variables, not yet validated adequately. We compared the impact of three referent groups: (i) HPV-negative, (ii) HPV-transient, (iii) HPV-mixed outcome on the risk estimates for 6M+ or 12M+ HR-HPV persistence as predictors of progressive disease. Generalized estimating equation models were used to estimate the strength of 6M+ and 12M+ HR-HPV persistence with disease progression to squamous intraepithelial lesions (SILs), cervical intraepithelial neoplasia (CIN) grade 1+, CIN2+, CIN/SIL endpoints, comparing three optional reference categories (i)-(iii) in a prospective sub-cohort of 1865 women from the combined New Independent States of the Former Soviet Union (NIS) and Latin American Screening (LAMS) studies cohort (n = 15,301). The RRs of these viral endpoints as predictors of progressive disease are affected by the length of viral persistence (6M+ or 12M+) and the surrogate endpoint (SIL, CIN1, CIN2, CIN/SIL). Most dramatic is the effect of the referent group used in risk estimates, with the HPV-negative referent group giving the highest and most consistent RRs for both 6M+ and 12M+ viral persistence, irrespective of which surrogate is used. In addition to deciding on whether to use 6M+ or 12M+ persistence criteria, and cytological, histological or combined surrogate endpoints, one should adopt the HPV-negative referent group as the gold standard in all future studies using viral persistence as the surrogate endpoint of progressive disease.
Int J STD AIDS 2011 Jun
PMID:Risk estimates for persistent high-risk human papillomavirus infections as surrogate endpoints of progressive cervical disease critically depend on reference category: analysis of the combined prospective cohort of the New Independent States of the Former Soviet Union and Latin American Screening studies. 2168 Jun 66

This study investigated the prevalence of adeno-associated virus (AAV) and human papillomavirus (HPV) DNA in cervical samples of HIV-seropositive and -seronegative women attending a clinic in south-eastern Brazil. Both viruses were investigated by polymerase chain reaction (PCR) and cytological exams were performed. AAV was typed by PCR and restriction fragment length polymorphism analysis. AAV prevalence was 19.7% (56/284), with 18.7% (21/112) and 20.3% (35/172) in HIV-positive and -negative women, respectively. AAV type 2 was the single virus type detected. AAV was detected with higher frequency in HPV-infected women (P < 0.05) as was HPV in HIV-positive women (P < 0.05). The AAV-HPV co-infected women showed a lower rate of atypical squamous cells of undetermined significance or cervical intraepithelial neoplasia development compared with those infected only with HPV. The prevalence of AAV2 confirms this type as the most common in human samples. This is the first report examining AAV in cervical samples of HIV-infected women and indicates that HIV infection does not appear to influence AAV prevalence or AAV-HPV co-infection.
Int J STD AIDS 2012 Apr
PMID:Adeno-associated virus may play a protective role against human papillomavirus-induced cervical lesions independent of HIV serostatus. 2258 49

To determine factors that influence excision treatment outcome and recurrence of cervical squamous intraepithelial lesions (SIL) in women living with HIV infection, we analysed 1848 women who underwent excision treatment of cervical SIL at Tygerberg Hospital, Cape Town, South Africa. We compared treatment failure defined as presence of cervical intraepithelial neoplasia (CIN) I (presence of CIN I or higher at first follow-up after excision treatment) and post-excision recurrence of lesions (at one year or later) between women of HIV-positive, -negative or unknown status and examined factors associated with excision treatment outcome and recurrence. HIV-infected women experienced higher treatment failure than uninfected women (53.8% versus 26.9%, P < 0.001). At treatment failure, more HIV-infected women had low-grade squamous intraepithelial lesion (LSIL) compared with uninfected women (64.9% versus 37.3%, P < 0.001). Treatment failure did not differ with the type of excision used in HIV-infected women. HIV-infected women were more likely to experience recurrence of lesions after excision treatment than uninfected women (hazard ratio 1.95, 95% confidence interval [CI] 1.59-2.39; P < 0.001). Antiretroviral therapy (ART) initiated before excision biopsy had a strong protective effect against recurrence (hazard ratio 0.70, 95% CI 0.55-0.89; P = 0.006). Our data suggest that women with cervical SIL initiated on ART earlier may be expected to have better long-term excision treatment outcome. Close follow-up should be maintained after cervical excision treatment, especially in a setting of high HIV prevalence.
Int J STD AIDS 2012 Dec
PMID:Impact of timing of antiretroviral therapy initiation on survival of cervical squamous intraepithelial lesions: a cohort analysis from South Africa. 2325 31

Tetraspanins are a heterogeneous group of 4-transmembrane proteins that segregate into so-called tetraspanin-enriched microdomains (TEMs) along with other cell surface proteins such as integrins. TEMs of various types are reportedly involved in the regulation of cell growth, migration and invasion of several tumour cell types, both as suppressors or supporting structures. Tetraspanin 1 (Tspan1, NET-1), a member of the transmembrane 4 superfamily (TM4SF) of tetraspanins, is overexpressed in high-grade cervical intraepithelial neoplasia (CIN) and terminal carcinomas but its precise function in the context of carcinoma of the cervix uteri is not known. Here, we present a comprehensive investigation of the role of tetraspanin 1 in the cervical cancer cell lines SiHa and HeLa. We document that tetraspanin 1 increases the invasive potential of cervical cancer cells, whereas proliferation, growth in soft agar and adhesion are largely unaffected. In line with the latter findings, our data exclude the participation of testraspanin in integrin-mediated activation of focal adhesion kinase (FAK), paxillin and phosphoinositide-3-kinase (PI3K) and in EGFR-dependent signalling to the Ras/Erk pathway. In conclusion, our data argue against a role for tetraspanin 1 as a genuine mediator of cell surface receptor signalling but rather document a role for tetraspanin 1 in the control of cervical cancer cell motility and invasion.
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PMID:Tetraspanin 1 promotes invasiveness of cervical cancer cells. 2375 16

Usual or undifferentiated type vulval intraepithelial neoplasia (VIN) is more common in young women and is usually associated with high-risk human papillomavirus infection. It is associated with the development of basaloid or warty squamous cell carcinoma. Studies have shown that HIV-positive women have an increased risk of VIN and invasive vulval carcinoma, but there is a paucity of data about this cohort of women. The objective of this study was to describe the clinical features and treatment responses of HIV-positive women diagnosed with VIN in a specialist vulval dermatology clinic. HIV-positive women diagnosed with VIN from 2007 to 2013 were retrospectively identified. Data were collected on demographics, clinical features, treatments and outcomes. Seven cases were retrospectively identified. The median CD4 cell count at presentation was 500 cells/mm3 (range 59-761). Five had multifocal VIN. Five were treated with imiquimod alone, one had surgical excision and one patient was treated with imiquimod and surgery. Five of the seven had complete resolution of disease. HIV-positive patients with VIN had good responses to treatment with imiquimod. They were likely to be stable on combination antiretroviral therapy at presentation, have multifocal disease and concurrent vaginal, anal or cervical intraepithelial neoplasia.
Int J STD AIDS 2016 12
PMID:Usual vulval intraepithelial neoplasia in HIV-positive women - a case series. 2647 32


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