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

Cervical cancer (CC) cells exhibit complex karyotypic alterations, which is consistent with deregulation of numerous critical genes in its formation and progression. To characterize this karyotypic complexity at the molecular level, we used cDNA array comparative genomic hybridization (aCGH) to analyze 29 CC cases and identified a number of over represented and deleted genes. The aCGH analysis revealed at least 17 recurrent amplicons and six common regions of deletions. These regions contain several known tumor-associated genes, such as those involved in transcription, apoptosis, cytoskeletal remodeling, ion-transport, drug metabolism, and immune response. Using the fluorescence in situ hybridization (FISH) approach we demonstrated the presence of high-level amplifications at the 8q24.3, 11q22.2, and 20q13 regions in CC cell lines. To identify amplification-associated genes that correspond to focal amplicons, we examined one or more genes in each of the 17 amplicons by Affymetrix U133A expression arrays and semiquantitative reverse-transcription PCR (RT-PCR) in 31 CC tumors. This analysis exhibited frequent and robust upregulated expression in CC relative to normal cervix for genes EPHB2 (1p36), CDCA8 (1p34.3), AIM2 (1q22-23), RFC4, MUC4, and HRASLS (3q27-29), SKP2 (5p12-13), CENTD3 (5q31.3), PTK2, RECQL4 (8q24), MMP1 and MMP13 (11q22.2), AKT1 (14q32.3), ABCC3 (17q21-22), SMARCA4 (19p13.3) LIG1 (19q13.3), UBE2C (20q13.1), SMC1L1 (Xp11), KIF4A (Xq12), TMSNB (Xq22), and CSAG2 (Xq28). Thus, the gene dosage and expression profiles generated here have enabled the identification of focal amplicons characteristic for the CC genome and facilitated the validation of relevant genes in these amplicons. These data, thus, form an important step toward the identification of biologically relevant genes in CC pathogenesis. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
 ...
PMID:Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes. 1724 65

This study was designed to determine the accuracy and agreement of a self-collection method using pad for human papillomavirus (HPV) DNA. One hundred and thirty-four patients at university hospitals voluntarily participated in the accuracy study, and 314 volunteers participated in the agreement study at local clinics. DNA was extracted and amplified using HPV L1 consensus primers designed for the direct sequencing. In the accuracy study, all samples were probed via histological examinations. With regard to the detection of squamous intraepithelial lesion (SIL), self-collection pad sampling displays sensitivity, of 76.9%, and specificity, of 93.3%. Three hundred and fourteen self-collection pad samples and the concurrent physicians' samples showed a 97.8% agreement, with a Kappa value of 0.9200. A new self-collection pad for the detection of HPV DNA appears to constitute an easy, rapid, and convenient alternative method for the cervical cancer screening of many women with the virtue of being incredible readily accessible.
Int J STD AIDS 2007 Mar
PMID:Pad - a new self-collection device for human papillomavirus. 1736 47

Infection of keratinocytes with high risk human Papilloma virus causes immortalization, and when followed by further mutations, leads to cervical cancer and other anogenital tumors. Here we monitor the progressive loss of robustness in an in vitro model of the early stages of transformation that comprises normal keratinocytes and progressive passages of HPV16 immortalized cells. As transformation progresses, the cells acquire higher proliferation rates and gain the ability to grow in soft agar. Concurrently, the cells lose robustness, becoming more sensitive to serum starvation and DNA damage by Cisplatin. Loss of robustness in the course of transformation correlates with significant reductions in the activities of the anti-apoptotic proteins PKB/Akt, Erk, Jnk and p38 both under normal growth conditions and upon stress. In parallel, loss of robustness is manifested by the shrinkage of the number of growth factors that can rescue starving cells from apoptosis, with the emergence of dependence solely on IGF1. Treatment with IGF1 activates PKB/Akt and Jnk and through them inhibits p53, rescuing the cells from starvation. We conclude that transformation in this model induces higher susceptibility of cells to stress due to reduced anti-apoptotic signaling and hyper-activation of p53 upon stress.
 ...
PMID:Loss of robustness and addiction to IGF1 during early keratinocyte transformation by human Papilloma virus 16. 1762 50

High-risk subtypes of human papillomavirus (HPV) are the main causative agents of cervical cancer, for which Chlamydia trachomatis (CT) may sometimes be a co-factor. Vaccines have been developed against some subtypes of human papillomavirus and a vaccine against CT is in development. The objective of this study was to determine the prevalence of the subtypes of HPV and CT in genitourinary (GU) medicine clinic attenders. In total, 1000 consecutive patients attending the GU clinic participated in this anonymized point-prevalence study. Urethral swabs from 437 men and urethral plus cervical swabs as a single specimen from 563 women were tested for the subtypes of both organisms. Nested major outer membrane protein (MOMP) polymerase chain reaction detected CT chromosomal DNA in 44/437 (10%) of the men and 73/563 (13%) of the women. Genotypes E, F, and D were the most common. In all, 55/437 (13%) of men and 244/563 (43%) of women were infected with at least one high-risk HPV type. In conclusion, the new HPV vaccines, Gardasil and Cervarix, would have protected against 58% and 45%, respectively, of the high-risk subtypes found in women in this population. The rate of high-risk HPV infection (43%) found in women in this study raises concern.
Int J STD AIDS 2007 Sep
PMID:Molecular epidemiology of genital human papillomavirus and Chlamydia trachomatis among patients attending a genitourinary medicine clinic - will vaccines protect? 1778 6

Cervical cancer (CxCa) is a long-term sequelae caused by persistent human papillomavirus (HPV) infection. Genetic susceptibility to the persistent infection and CxCa is associated with certain human leucocyte antigen (HLA) types. The same susceptibility genes may also determine whether a woman will be protected against the persistent infection and against CxCa by HPV vaccination or not. A systematic review of literature identified following HLAs to be associated with CxCa: A11 (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.1-2.0); B7 (1.5, 1.1-2.0); B15 (0.6, 0.4-0.8); DR2 (1.2, 1.1-1.4) and DR6 (0.6, 0.5-0.8). In the Caucasian population, HLA-B7 and DR6, and DR2 and B15 antigens showed at least borderline associations. In view of a bone marrow donor registry at the Finnish Red Cross and the Finnish Cancer Registry, we created geographic distribution maps of index HLA frequencies and CxCa incidence in the fertile-aged Finnish population. Increased incidence of CxCa was found in a region of western coastal Finland, where frequency of two CxCa susceptibility genes (HLA-DR2 and B7) was increased, and frequency of one CxCa resistance gene (HLA-B15) was decreased. Whether or not HLA type determines also regional susceptibility to persistent HPV infection, and the success of HPV vaccination in preventing both the persistent infection and CxCa warrants further investigation.
Int J STD AIDS 2007 Oct
PMID:Geographic distribution of cervical cancer-associated human leucocyte antigens and cervical cancer incidence in Finland. 1794 45

The aim of the study was to determine human papillomavirus (HPV) type-distribution in the cervix of Chinese women, and to estimate the potential future impact of HPV prophylactic vaccines for cervical cancer prevention in China. A total of 32 studies using polymerase chain reaction for HPV detection were included in the meta-analysis, including 2844 invasive cervical cancer (ICC), 820 high-grade squamous intraepithelial lesions (HSIL), 432 low-grade squamous intraepithelial lesions (LSIL) and 2902 women with normal cytology/histology. The overall and type-specific HPV prevalence of 18 HPV types (HPV 6, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 70, 73 and 82 of different cervical stages) were estimated. Overall HPV prevalence was 83.7%, 66.2%, 61.3% and 11.2% in ICC, HSIL, LSIL and normal, respectively. HPV 16 was the predominant type in all cervical stages. Estimated HPV 16/18 positive fractions in ICC, HSIL, LSIL and normal were 69.7%, 45.5%, 32.23% and 4.6%, respectively. HPV-16/18 vaccine has the 69.7% potential prevention in ICC. HPV 58 and 52 were the priority HPV types in Chinese women.
Int J STD AIDS 2008 Feb
PMID:Human papillomavirus type-distribution in the cervix of Chinese women: a meta-analysis. 1833 63

High-risk genital human papillomavirus (HPV) infection is aetiologically linked to cervical cancer; however, data on the prevalence and determinants of high-risk HPV infection in Uganda are limited. We conducted a population-based cross-sectional survey among 18-49-year-old women in rural Southwest Uganda. The primary outcome was presence or absence of high-risk HPV DNA (for genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68) in the genital secretions as determined by HPV DNA Hybrid Capture 2 assay (Digene Corp, Beltsville, MD, USA). In 314 women who participated, the prevalence of high-risk HPV was 17.2% (54/314; 95% confidence interval [CI]: 13-21). Older women had a lower proportion of high-risk HPV infection; with a 9% decrease in the odds ratio (OR) of high-risk HPV infection per year increase in age (OR = 0.91; 95% CI: 0.86, 0.96). The odds of detecting high-risk HPV infection was higher among women who were previously tested positive for HIV (OR = 12.1; 95% CI: 2.8, 52.3). In this population of rural Ugandan women, the prevalence of high-risk cervical HPV infection was high. Information on predictors of high-risk HPV infection and intention to receive a vaccine can guide future immunization initiatives for young sexually active women.
Int J STD AIDS 2008 Sep
PMID:Prevalence and predictors of high-risk human papillomavirus infection in a population-based sample of women in rural Uganda. 1872 51

Intra-type genome variations of high risk Human papillomavirus (HPV) have been associated with a differential threat for cervical cancer development. In this work, the effect of HPV18 E6 isolates in Akt/PKB and Mitogen-associated protein kinase (MAPKs) signaling pathways and its implication in cell proliferation were analyzed. E6 from HPV types 16 and 18 are able to bind and promote degradation of Human disc large (hDlg). Our results show that E6 variants differentially modulate hDlg degradation, rebounding in levels of activated PTEN and PKB. HPV18 E6 variants are also able to upregulate phospho-PI3K protein, strongly correlating with activated MAPKs and cell proliferation. Data was supported by the effect of E6 silencing in HPV18-containing HeLa cells, as well as hDlg silencing in the tested cells. Results suggest that HPV18 intra-type variations may derive in differential abilities to activate cell-signaling pathways such as Akt/PKB and MAPKs, directly involved in cell survival and proliferation.
 ...
PMID:E6 variants of human papillomavirus 18 differentially modulate the protein kinase B/phosphatidylinositol 3-kinase (akt/PI3K) signaling pathway. 1900 61

The STD including HPV infection has been worldwide spread in young persons. HPV has been recognized as a necessary cause of cervical cancer. It is highly prevalent sexually active persons and traceable in its natural history with a recent advanced technology. This technology has provided the basis of improved cervical cancer screening and management protocol. It has also been shown that the major virion protein of HPV alone, once replicated in convenient expression system, produces immunogens that are able to induce powerful immune responses. Now, HPV-related diseases can be prevented by the HPV-vaccines which are commercially available.
 ...
PMID:[Diagnosis of HPV-related diseases]. 1917 56

The aim of the study was to investigate knowledge of and attitudes to sexually transmitted infection (STI) and STI prevention with special focus on human papillomavirus (HPV) and the new vaccine against HPV, among 16-year-old high school students in a Swedish context. A study-specific questionnaire was distributed to 572 first year high school students from five different high schools in a medium-sized town in Sweden. The students lacked knowledge of HPV and its association with cervical cancer. Similarly, their knowledge of the new vaccine was limited. Their attitude to condom use when having sex with a new partner was positive, but decreased if oral contraceptives were used and if they were vaccinated against an STI. The main source of information was the school, followed by youth clinics and the media. The results highlight the clinical importance for school nurses and personnel at youth clinics to inform adolescents about HPV and its association with cancer.
Int J STD AIDS 2009 Feb
PMID:Knowledge of human papillomavirus and attitudes to vaccination among Swedish high school students. 2060 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>