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1.
Virology ; 446(1-2): 378-88, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24074602

RESUMO

The incidence of human papillomavirus (HPV)-associated epithelial lesions is substantially higher in human immunodeficiency virus (HIV)-infected individuals than in HIV-uninfected individuals. The molecular mechanisms underlying the increased risk of HPV infection in HIV-infected individuals are poorly understood. We found that HIV proteins tat and gp120 were expressed within the oral and anal mucosal epithelial microenvironment of HIV-infected individuals. Expression of HIV proteins in the mucosal epithelium was correlated with the disruption of epithelial tight junctions (TJ). Treatment of polarized oral, cervical and anal epithelial cells, and oral tissue explants with tat and gp120 led to disruption of epithelial TJ and increased HPV pseudovirion (PsV) paracellular penetration in to the epithelium. PsV entry was observed in the basal/parabasal cells, the cells in which the HPV life cycle is initiated. Our data suggest that HIV-associated TJ disruption of mucosal epithelia may potentiate HPV infection and subsequent development of HPV-associated neoplasia.


Assuntos
Epitélio/patologia , Epitélio/virologia , Infecções por HIV/complicações , Mucosa Intestinal/patologia , Mucosa Intestinal/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/virologia , Células Cultivadas , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Técnicas de Cultura de Órgãos , Infecções por Papillomavirus/patologia , Junções Íntimas/fisiologia
2.
Cancer Prev Res (Phila) ; 6(8): 774-81, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23639481

RESUMO

Women with Lynch syndrome have a 40% to 60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have shown that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown whether they are effective in women with Lynch syndrome. Asymptomatic women ages 25 to 50 with Lynch syndrome were randomized to receive the progestin compounds Depo-Provera (depo-MPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were conducted before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depo-MPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results show that women with Lynch syndrome do show an endometrial response to short-term exogenous progestins, suggesting that OCP and depo-MPA may be reasonable chemopreventive agents in this high-risk patient population.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Anticoncepcionais Orais/uso terapêutico , Neoplasias do Endométrio/prevenção & controle , Acetato de Medroxiprogesterona/uso terapêutico , Adulto , Biomarcadores Tumorais/genética , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/metabolismo , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Mutação/genética , Prognóstico , Estudos Prospectivos
3.
Carcinogenesis ; 31(9): 1620-6, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20554747

RESUMO

Endometrial cancer (EC) is a steroid hormone-dependent cancer. Uridine 5'-diphospho-glucuronosyltransferase enzymes conjugate and detoxify endogenous and exogenous steroid hormones and environmental carcinogens. Among these enzymes, the function of UGT2B17 is unknown except for glucuronidation. The messenger RNA expression of UGT2B17 and myeloid cell leukemia-1 (Mcl-1) was significantly increased in EC tissues compared with matched normal endometrial tissues. Therefore, we focused on the function of UGT2B17 in EC. A total of nine patients with confirmed EC were enrolled in this study to investigate the expression of UGT2B17 and target genes. EC cell lines were used for functional tests including cell growth, invasion, apoptosis and cell cycle analyses. To find the target genes of UGT2B17, we performed microarray analysis to see which genes were upregulated or downregulated by UGT2B17-transfected cells. Functional analysis showed decreased numbers of viable cells and increased numbers of apoptotic cells in si-UGT2B17-transfected Ishikawa cells. Among microarray target genes, Mcl-1 was significantly downregulated in si-UGT2B17-transfected cells. We also found upregulation of Puma protein, a target of Mcl-1, in si-UGT2B17-transfected cells. This is the first report to show that UGT2B17 and Mcl-1 expression are upregulated in EC tissues and that UGT2B17 depletion induces inhibition of cell growth and apoptosis in EC cells through Mcl-1 downregulation.


Assuntos
Adenocarcinoma/enzimologia , Neoplasias do Endométrio/enzimologia , Regulação Enzimológica da Expressão Gênica , Glucuronosiltransferase/fisiologia , Adenocarcinoma/patologia , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Estudos de Casos e Controles , Adesão Celular , Ciclo Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Neoplasias do Endométrio/patologia , Feminino , Perfilação da Expressão Gênica , Genótipo , Humanos , Antígenos de Histocompatibilidade Menor , Proteína de Sequência 1 de Leucemia de Células Mieloides , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/genética , RNA Interferente Pequeno/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
4.
J Low Genit Tract Dis ; 14(2): 81-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20354414

RESUMO

OBJECTIVE: To explore, identify, and describe the perception of uncertainty over time in college-aged women experiencing the unexpected event of an abnormal Pap smear with human papillomavirus (HPV). METHODS: Eighty-eight female patients, who had abnormal Pap smear and had indications for colposcopy, were recruited from a Student Health Service and consented for study participation. Uncertainty levels were measured over time. Relationships among uncertainty, knowledge of HPV, body attitude and moods, coping strategies, and follow-up were evaluated. RESULTS: The relationship between uncertainty and coping strategies was supported in the emotion-focused path as predicted but not in the problem-focused path. Evidence of adaptation to uncertainty through emotion-focused coping was found in the significant relationship between emotion-focused coping and body attitude. Similarly, there was a significant relationship between emotion-focused coping and moods in the path analysis and in correlations with the subcategories of positive and negative moods. The problem-focused indirect path from uncertainty to adaptation showed no significant relationship. Likewise, uncertainty also had no significant direct effect on body attitude or promptness of follow-up but did have a direct impact on moods. The direct path from previous knowledge to uncertainty was not supported. CONCLUSIONS: The presence of uncertainty over time was established in this study population. Statistically significant relationships were confirmed among uncertainty, emotion-focused coping strategies, and adaptation in a group of young women experiencing a mildly abnormal Pap smear.


Assuntos
Teste de Papanicolaou , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/psicologia , Incerteza , Esfregaço Vaginal/psicologia , Adaptação Psicológica/fisiologia , Adulto , Afeto/fisiologia , Feminino , Humanos , Estudantes , Adulto Jovem
5.
Obstet Gynecol Clin North Am ; 36(1): 187-200, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19344856

RESUMO

The relationship between cervical cancer and human papillomavirus (HPV) is well known. Like cervical cancer, anal cancer is preceded by a series of precancerous changes, raising the possibility that like cervical cancer, anal cancer can be prevented. Further, given the known risk factors for anal cancer, prevention efforts could be targeted to high-risk groups, providing a unique example of a screening program targeted to high-risk individuals. This article describes the epidemiology of anal HPV infection, anal intraepithelial neoplasia, and anal cancer among men and women, as well as current efforts to prevent anal cancers.


Assuntos
Canal Anal/patologia , Neoplasias do Ânus/epidemiologia , Colonoscopia/métodos , Papillomavirus Humano 11 , Infecções por Papillomavirus/epidemiologia , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Canal Anal/virologia , Neoplasias do Ânus/etiologia , Neoplasias do Ânus/patologia , Diagnóstico Diferencial , Feminino , Humanos , Incidência , Masculino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Fatores de Risco , Doenças Virais Sexualmente Transmissíveis/complicações , Doenças Virais Sexualmente Transmissíveis/diagnóstico , Estados Unidos/epidemiologia
6.
Gynecol Oncol ; 111(1): 137-43, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18703220

RESUMO

OBJECTIVES: While there are many psychosocial interventions for cancer patients, few are brief in nature. The aim of this study was to investigate the usefulness of a single-visit psychosocial intervention for gynecologic cancer patients. METHODS: One hundred women attending a gynecologic cancer clinic as new patients were randomized to receive no intervention or a one-time meeting with a psychologist who discussed issues and concerns the woman might have about her cancer diagnosis. Thirty-eight of the women had a current or previous cancer. The women were given questionnaires measuring mood and quality of life at baseline, two weeks and three months after the intervention. RESULTS: At baseline, 43 of the women in the control group completed questionnaires, as did 45 women randomized to the intervention. 21 of these women received the intervention. Women who received the intervention had greater decreases in anxiety, depression and overall distress over time. The control group also had decreases in anxiety and overall distress over time, but had an increase in depression. The women in the intervention group increased in physical, emotional, functional, and overall well being, while the control group only had a slight increase in overall well being over time. The difference between the groups in emotional well being at Time 2 approached significance (p=.08). The intervention group had increases in positive coping at Time 2, while the control group decreased (p's ranged from .02-.10). Three month follow-up data were available for 23 women in the control group and 15 in the intervention group. At Time 3 functional well being was significantly higher in the intervention group (p=.04). Information seeking and affect regulation remained higher in the intervention than the control group (p's=.002 and .02, respectively). When the women with cancer or previous cancer were examined, significant differences were seen for affect regulation at baseline (p=.0007), and anger two weeks later (p=.04), with the women in the control group being more angry. Utilization of other cancer resources was low with 12% of the women reporting that they used the Cancer Resource Center. CONCLUSIONS: The results of this study show that there was a positive effect towards coping and quality of life for a one-time psychosocial intervention after the first visit to a gynecologic oncology practice. Women who were randomized to the intervention but did not go were more distressed at baseline than the women who did go. This suggests that incorporating psychosocial services as an integrated part of the new patient consultation may be very important to address patient's distress. Future studies with larger sample sizes may reveal more significant differences. Strategies to overcome the poor utilization of the cancer resource center are also clearly needed to improve awareness of these resources.


Assuntos
Neoplasias dos Genitais Femininos/psicologia , Neoplasias dos Genitais Femininos/terapia , Adaptação Psicológica , Adulto , Afeto , Idoso , Ansiedade/etiologia , Confusão/etiologia , Confusão/terapia , Depressão/etiologia , Depressão/terapia , Fadiga/etiologia , Feminino , Neoplasias dos Genitais Femininos/complicações , Humanos , Pessoa de Meia-Idade , Qualidade de Vida
8.
Obstet Gynecol Surv ; 62(8): 548-55, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17634156

RESUMO

The short- and long-term effects of the widespread use of diethylstilbestrol (DES) over 3 decades have become a distant memory for many clinicians. Others are too young to remember the flurry of activity in the early 1970s on the part of many medical centers to identify the offspring of women who were prescribed DES during their pregnancies. This medication was given in an attempt to prevent multiple pregnancy-related problems such as miscarriage, premature birth, and abnormal bleeding. The recognition of the association of DES with an increased incidence of cervical and vaginal cancers in very young women led the Food and Drug Administration to ban its use during pregnancy in 1971. Other pregnancy-related problems for the daughters and genitourinary tract changes in the sons did not become apparent until years later. Ongoing follow-up of these offspring has raised concerns for their future as well as their mothers' future. Clinicians need to be up-to-date with current knowledge regarding risks for cancer and other health-related issues.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Dietilestilbestrol/efeitos adversos , Doenças dos Genitais Femininos/induzido quimicamente , Doenças dos Genitais Masculinos/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Adenocarcinoma/induzido quimicamente , Feminino , Humanos , Infertilidade/induzido quimicamente , Masculino , Gravidez , Resultado da Gravidez , Risco , Neoplasias Vaginais/induzido quimicamente
9.
J Low Genit Tract Dis ; 10(4): 213-8, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17012985

RESUMO

OBJECTIVE: Little is known about effects of vaginal lubricants with barrier contraceptives on detection of sexually transmissible infections. We hypothesized that Replens gel used with a diaphragm would neither inhibit human papillomavirus (HPV) detection in cervical samples and chlamydia (CT) and gonorrhea (GC) detection in urine samples, nor affect cervical cytology quality. MATERIALS AND METHODS: After a clinician-collected cervical sample and a self-collected vaginal sample for HPV detection ("pregel" specimens), women placed a diaphragm containing Replens gel into the vagina. Participants (n = 77) removed the diaphragm after 6 hours and performed vaginal HPV self-sampling at several time points thereafter. Clinicians performed cervical cytology sampling and HPV testing ("postgel" specimens) 24 hours after diaphragm removal. Pregel and postgel specimens were analyzed with and without added SiHa cells (source of defined numbers of HPV16 genomes). HPV was detected by polymerase chain reaction using MY09/11 primers. Urine samples were obtained for CT and GC testing. Proportions of samples testing positive were compared using relative risk (RR) regression models. RESULTS: Proportions with detectable HPV in the clinician-collected cervical pregel and postgel samples were not statistically different for samples with added SiHa cells (88.3% vs 93.2%, RR = 1.06, 95% confidence interval = 0.96-1.14) or for native HPV infection (32.9% vs 28.2%, RR = 0.87, 95% confidence interval = 0.71-1.06). In self-collected vaginal postgel samples, there was no trend for decreased HPV detection after gel exposure. Gel affected neither urine tests for CT and GC nor cytological quality. CONCLUSIONS: Recent Replens gel use with a diaphragm does not inhibit cervical HPV testing, urine testing for CT and GC, or cervical cytology quality.


Assuntos
Dispositivos Anticoncepcionais Femininos/estatística & dados numéricos , Doenças dos Genitais Femininos/diagnóstico , Papillomavirus Humano 16/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Cremes, Espumas e Géis Vaginais/uso terapêutico , Adolescente , Adulto , DNA Viral/análise , Diagnóstico Diferencial , Feminino , Doenças dos Genitais Femininos/virologia , Papillomavirus Humano 16/genética , Humanos , Lipídeos/uso terapêutico , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Estudos Retrospectivos
10.
N Engl J Med ; 354(3): 261-9, 2006 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-16421367

RESUMO

BACKGROUND: Women with the Lynch syndrome (hereditary nonpolyposis colorectal cancer) have a 40 to 60 percent lifetime risk of endometrial cancer and a 10 to 12 percent lifetime risk of ovarian cancer. The benefit of prophylactic gynecologic surgery for women with this syndrome has been uncertain. We designed this study to determine the reduction in the risk of gynecologic cancers associated with prophylactic hysterectomy and bilateral salpingo-oophorectomy in women with the Lynch syndrome. METHODS: Three hundred fifteen women with documented germ-line mutations associated with the Lynch syndrome were identified. Women who had undergone prophylactic hysterectomy (61 women) and women who had undergone prophylactic bilateral salpingo-oophorectomy (47 women) were matched with mutation-positive women who had not undergone the procedure in question (210 women for the analysis of endometrial cancer and 223 for the analysis of ovarian cancer). Women who had undergone prophylactic surgery and their matched controls were followed from the date of the surgery until the occurrence of cancer or until the data were censored at the time of the last follow-up visit. RESULTS: There were no occurrences of endometrial, ovarian, or primary peritoneal cancer among the women who had undergone prophylactic surgery. Endometrial cancer was diagnosed in 69 women in the control group (33 percent), for an incidence density of 0.045 per woman-year, yielding a prevented fraction (the proportion of potential new cancers prevented) of 100 percent (95 percent confidence interval, 90 to 100 percent). Ovarian cancer was diagnosed in 12 women in the control group (5 percent), for an incidence density of 0.005 per woman-year, yielding a prevented fraction of 100 percent (95 percent confidence interval, -62 to 100 percent). CONCLUSIONS: These findings suggest that prophylactic hysterectomy with bilateral salpingo-oophorectomy is an effective strategy for preventing endometrial and ovarian cancer in women with the Lynch syndrome.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/cirurgia , Neoplasias do Endométrio/prevenção & controle , Histerectomia , Neoplasias Ovarianas/prevenção & controle , Ovariectomia , Adulto , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Feminino , Mutação em Linhagem Germinativa , Humanos , Incidência , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologia , Neoplasias Peritoneais/epidemiologia , Neoplasias Peritoneais/etiologia , Neoplasias Peritoneais/prevenção & controle , Complicações Pós-Operatórias , Estudos Retrospectivos , Risco
11.
J Low Genit Tract Dis ; 9(1): 11-8, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15870516

RESUMO

Diethylstilbestrol (DES), a nonsteroidal estrogen, was widely used in the United States from 1940 through 1971 to prevent pregnancy loss. In the late 1960s, an association was made with an increased incidence of clear cell adenocarcinoma in young women exposed in utero to DES. Additional study of these women over the next 35 years has shown an increased risk of other health problems including intraepithelial neoplasia, ectopic pregnancy, first trimester spontaneous abortion and second trimester pregnancy loss. The National Institutes of Health continues to fund studies to follow cohorts of DES-exposed mothers, daughters, sons and third generation children. The Centers for Disease Control have conducted a large DES Education Project and have established guidelines for management. The following six cases studies illustrate common problems seen in DES exposed daughters and management of problems encountered.


Assuntos
Dietilestilbestrol/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Adenocarcinoma de Células Claras/induzido quimicamente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez/induzido quimicamente , Gravidez Ectópica/induzido quimicamente , Fatores de Tempo , Neoplasias do Colo do Útero/induzido quimicamente , Neoplasias Vaginais/induzido quimicamente , Displasia do Colo do Útero/induzido quimicamente
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