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)

Infection with human papillomavirus (HPV) is one of the major preventable causes of cancer world-wide. Rapid increase in cervical cancer incidence also in some western countries with cervical cancer screening programmes is probably due to increase in background exposure to HPV in the young. HPV vaccines are in clinical trials and the results have been promising, but due to assortative transmission of the infection and multiple HPV types the effect of large-scale immunization on their spread will vary between different populations and by HPV type. Thus, it is difficult to predict the effect of vaccination on cancer incidence on the basis of efficacy trials only. In the following evaluation of population level, effectiveness of vaccination on cervical cancer incidence (1) and HPV prevalence (2) by combined cluster/individually randomized trials (1) and cluster/community randomized trials (2) are described.
Int J STD AIDS 2003 Dec
PMID:Effectiveness of preventive human papillomavirus vaccination. 1467 83

Association between the p53 codon 72 polymorphism and cervical cancer remains unresolved. We determined the association between the polymorphism and risk of human papillomavirus (HPV) persistence. The polymorphism was detected by restriction enzyme digestion following p53 amplification and HPV detection by the PGMY 09/11 primer set followed by reverse line blot hybridization: 3371 samples were analysed. HPV persistence was assessed on a subset of samples collected at baseline, four and 10 months (n =442). Highly significant differences were observed between ethnic groups (P <0.005). No associations were found between P53 arginine and cytological grade in women infected with any HPV or any oncogenic HPV, despite adjustment for ethnicity. These results were sustained even when HPV-negative women were used as controls. Persistence for any or oncogenic HPV infection was not associated with the polymorphism, irrespective or ethnicity adjustment. Our findings do not support a role for this polymorphism conferring elevated risk for HPV-related disease.
Int J STD AIDS 2003 Dec
PMID:Ethnic variation of the P53 codon 72 polymorphism, HPV persistence, and cervical cancer risk. 1467 86

We established 2 novel human cell lines (GCCOT-1, GCCRK) from glassy cell carcinoma. Both cell lines showed dual tendencies of glandular and squamous differentiation, and thus possess the characteristics resembling reserve cells, the putative origin of most carcinomas arising from the uterine cervix. HPV type 18 DNA including E6-E7, which is commonly found in cell types other than squamous cell carcinoma of uterine cervix, was detected in both cell lines. We analyzed gene copy number alterations of the 2 cell lines using conventional comparative genomic hybridization (CGH) coupled with array-based CGH. Among the putative oncogenes demonstrating copy number gain in both cell lines, FGR(SRC2) at 1p36.2-1 and LAMC2 at 1q25-31 have not been reported to show amplification in previous analyses of conventional cervical cell lines. These oncogenes are thus speculated to be directly associated with oncogenesis of glassy cell carcinoma. On the other hand, among the putative suppressor genes demonstrating copy number loss in both cell lines, the 9q region, ATM at 11q22.3, and CYLD at 16q12-13 have not been reported to show loss in conventional cervical cancer cell lines. These sites are speculated to be important as tumor suppressors directly associated with oncogenesis of glassy cell carcinoma. This study suggests for the first time that together with the presence of HPV type 18, alterations at the above sites are closely associated with oncogenesis of glassy cell carcinoma, a special type of carcinoma in the uterine cervix.
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PMID:Conventional and array-based comparative genomic hybridization analyses of novel cell lines harboring HPV18 from glassy cell carcinoma of the uterine cervix. 1501 Aug 38

Activation of the interleukin-2 receptor (IL-2R) induces signalling cascades promoting T cell proliferation. However, signal transduction pathways triggered in IL-2R-expressing solid tumours are unknown. This report shows that human papillomavirus (HPV)-associated cervical cancer cells express an IL-2R composed of beta and gamma chains (IL-2Rbetagamma), and that IL-2-mediated activation increases the phosphorylation of JAK3 and STAT5, stimulating cell proliferation. Interestingly, endogenous IL-2 is not produced by these cells, suggesting the activation of IL-2Rbetagamma by an alternative mechanism. Accordingly, we found that Stem Cell Factor (SCF)-activated c-Kit induces phosphorylation of the IL-2Rbeta chain in the absence of IL-2. Moreover, inhibition of IL-2Rbeta phosphorylation by blocking c-Kit tyrosine kinase activity abolishes both, IL-2 and SCF-mediated proliferation. Thus, these results demonstrate that IL-2 triggers a JAK3/STAT5 cascade in HPV-associated cervical cancer cells expressing IL-2Rbetagamma, and that this receptor can be alternatively activated by SCF-activated c-Kit in the absence of IL-2.
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PMID:Interleukin-2 (IL-2) receptor-betagamma signalling is activated by c-Kit in the absence of IL-2, or by exogenous IL-2 via JAK3/STAT5 in human papillomavirus-associated cervical cancer. 1533 23

Recent studies suggest that erythropoietin plays an important role in the process of neoplastic transformation and malignant phenotype progression observed in malignancy. To study the role of erythropoietin and its receptor (EPOR) on the response of cancer cells in vitro, we used two solid tumor cell lines, namely the human malignant glioma cell line U87 and the primary cervical cancer cell line HT100. All experiments were done with heat-inactivated fetal bovine serum in order to inactivate any endogenous bovine erythropoietin. The expression of the EPOR in these cells was confirmed with immunoblot techniques. The addition of exogenous recombinant human erythropoietin (rhEPO) induces the cancer cells to become more resistant to ionizing radiation and to cisplatin. Furthermore, this rhEPO-induced resistance to ionizing radiation and to cisplatin was reversed by the addition of tyrphostin (AG490), an inhibitor of JAK2. Our findings indicate that rhEPO result in a significant, JAK2-dependent, in vitro resistance to ionizing radiation and to cisplatin in the human cancer cells lines studied in this report.
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PMID:Erythropoietin induces cancer cell resistance to ionizing radiation and to cisplatin. 1563 45

In many middle-income countries with a high incidence of cervical cancer, organized screening programmes with the Pap test are being planned. We assessed the knowledge of, and attitudes towards, cervical screening among 63 doctors and 102 randomly selected community members in Trinidad where screening is still opportunistic. Doctors were well informed about cervical cancer, but not all knew the approximate specificity of the Pap test. Many did not routinely discuss the benefits and disadvantages of screening with their clients. Most women had heard of the Pap test, but only 56% knew its purpose; 25% would not participate in screening, stating reasons such as being in menopause or not having symptoms. More information about the aim of screening and the purpose of the Pap test must be communicated. Doctors need to keep their knowledge on screening up-to-date, and offer counselling that helps women to make an informed decision whether or not to participate in screening.
Int J STD AIDS 2005 Mar
PMID:'Have a Pap smear!'--doctors, their clients, and opportunistic cervical cancer screening. 1582 24

The incidence of cervical cancer increases with age among USA Hispanics and women living in Latin America starting in the fourth decade of life. We conducted a study of women > or = 40 living at the USA-Mexico border to determine the prevalence and risk factors for human papillomavirus (HPV) infection detected by polymerase chain reaction. In all, 9.2% of participants tested HPV positive. Compared with women aged 50-59, odds ratios of 8.82 and 6.67 were observed for women > or = 60 and 40-49, respectively. Among women aged 40-49, both oncogenic and non-oncogenic HPV infections were detected; however, women > or = 60 were positive for predominantly oncogenic genotypes. HPV risk significantly increased with > or = 2 lifetime sexual partners in adjusted models. These data suggest that the prevalence of HPV infection may have a second peak among post-menopausal Hispanic women.
Int J STD AIDS 2005 Mar
PMID:Human papillomavirus prevalence at the USA-Mexico border among women 40 years of age and older. 1582 27

To search for a marker that predicts the efficacy of radiation therapy in human cervical cancer, gene expression profiles between parental SiHa cervical cancer cells and radiation-resistant SiHa/R cells have been compared by the microarray technique. Microarray and Northern blot analyses demonstrated that the ICAM-3 expression was upregulated in SiHa/R cells. This increased expression of ICAM-3 in SiHa cells enhanced cell survival by about 34.3% after a 2 Gy dosage of radiation. In addition, SiHa/ICAM-3 cells showed a 2.45-fold higher level of FAK phosphorylation than that of the control cells. In tumor specimens, ICAM-3 staining was restricted to tumor stromal endothelial cells and lymphocytes. The overexpression of ICAM-3 was significantly more frequent in radiation-resistant cervical cancer specimens when compared with radiation-sensitive specimens (83.3% vs. 35.3%; p = 0.015). With these observations, we can suggest that an increased expression of ICAM-3 is associated with radiation resistance in cervical cancer cells and the expression of ICAM-3 can be used as a valuable biomarker to predict the radiation resistance in cervical cancer that occurs during radiotherapy.
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PMID:Increased expression of ICAM-3 is associated with radiation resistance in cervical cancer. 1588 Mar 73

Women in developing countries often present for medical care with advanced cervical cancer, although this condition is preventable through regular screening and early treatment. This study sought to identify the prevalence and risk factors for cervical dyskaryosis among women in Zimbabwe with and without HIV. In a cross-sectional study, 200 consenting women were screened for cervical dyskaryosis and sexually transmitted infections (STI). The relationship between various risk factors for cervical dyskaryosis was examined. The overall prevalence of cervical dyskaryosis was high (19%), and significantly higher among HIV-infected women at 30% compared with 13% among seronegative women, with a peak at a younger age among seropositive women. Use of intravaginal herbs, practising intravaginal cleansing, being single, a history of three or more lifetime sexual partners and a history of previous STI were associated with cervical dysplasia. The high frequency of cervical abnormality lends weight to the demand for implementation of regular screening programmes and health education.
Int J STD AIDS 2005 Dec
PMID:Cervical dyskaryosis among women with and without HIV: prevalence and risk factors. 1633 59

Genital human papillomavirus (HPV) infection is the most common sexually transmitted virus in the United States, causing genital warts, cervical cell abnormalities, and cervical cancer in women. To inform HPV education efforts, 35 focus groups were conducted with members of the general public, stratified by gender, race/ethnicity, and urban/rural location. Focus groups explored participants' knowledge, attitudes, and beliefs about HPV and a hypothetical HPV vaccine as well as their communication preferences for HPV-related educational messages. Audience awareness and knowledge of HPV were low across all groups. This, along with an apparent STD-associated stigma, served as barriers to participants' hypothetical acceptance of a future vaccine. Although information about HPV's high prevalence and link to cervical cancer motivated participants to learn more about HPV, it also produced audience fear and anxiety. This research suggests that HPV- and HPV-vaccine-related education efforts must be approached with extreme caution. Other practical implications are discussed.
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PMID:Exploring the knowledge, attitudes, beliefs, and communication preferences of the general public regarding HPV: findings from CDC focus group research and implications for practice. 1700 Jun 22


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