Classical and non-classical HLA molecules and p16(INK4a) expression in precursors lesions and invasive cervical cancer

Objectives: Viruses and turnout cells may regulate the expression of HLA molecules on the cell surface to escape immune system surveillance. Absence of classical HLA class I molecules may impair the action of specific cytotoxic cells, whereas non-classical HLA class I molecules may regulate innate and adaptive immune cells. We assess here the possible associations between classical/non-classical class I HLA and p16(INK4a) molecule expression in cervical biopsies of women infected with HPV, stratified according to grade of the lesion and HPV type. Study design: Cervical biopsies (N = 74) presenting cervical intraepithelial neoplasia grade 1 (CIN1) (n = 31), CIN2-3 (n = 19), and invasive cancer (n = 14) were evaluated alongside 10 normal cervical specimens. Results: HLA-A/B/C/G staining was observed in the early stages of HPV infection. A significant association was detected between HLA-A/B/C staining and HPV16/18 infection (OR = 0.12, 95%CI: 0.0163-0.7899; p = 0.04). HLA-E expression increased with the progression of the lesion (chi(2)-test for trend = 4.01; p = 0.05), and a significant association was found between HLA-E staining and HPV16/18 infection (OR = 11.25, 95%CI: 2.324-54.465; p = 0.003). Irrespective of the grade of the lesion, HLA-A/B/C staining and p16(INK4a) presented a good concordance (Kappa: 0.67). Conclusions: HLA-E overexpression seemed to be associated with invasive cancer and HPV16/18 infection. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

A pilot case-control association study of cytokine polymorphisms in Brazilian women presenting with HPV-related cervical lesions

Objective and study design: A case-control study was conducted on 42 Brazilian women presenting with human papilloma virus (HPV) infection and cervical lesion and 87 HPV-negative women to evaluate single nucleotide polymorphisms observed in TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma genes. Results and conclusion: No significant association was observed on the cytokine polymorphisms analyzed in this series. Larger studies using cytokine polymorphisms may be useful for providing further information regarding their influence or not in HPV-related cervical lesions. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Differentially expressed genes in eutopic and ectopic endometrium of women with endometriosis

Objective: To elucidate the potential mechanisms involved in the physiopathology of endometriosis. We analyzed the differential gene expression profiles of eutopic and ectopic tissues from women with endometriosis. Design: Prospective laboratory study. Setting: University hospital. Patient(s): Seventeen patients in whom endometriosis was diagnosed and 11 healthy fertile women. Intervention(s): Endometrial biopsy specimens from the endometrium of healthy women without endometriosis and from the eutopic and ectopic endometrium tissues of patients with endometriosis were obtained in the early proliferative phase of the menstrual cycle. Main Outcome Measure(s): Six paired samples of eutopic and ectopic tissue were analyzed by subtractive hybridization. To evaluate the expression of genes found by rapid subtraction hybridization methods, we measured CTGF, SPARC, MYC, MMP and IGFBP1 genes by real-time polymerase chain reaction in all samples. Result(s): This study identified 291 deregulated genes in the endometriotic lesions. Significant expression differences were obtained for SPARC, MYC, and IGFBP1 in the peritoneal lesions and for MMP3 in the ovarian endometriomas. Additionally, significant differences were obtained for SPARC and IGFBP1 between the peritoneal and ovarian lesions. No significant differences were found for the studied genes between the control and the eutopic endometrium. Conclusion(s): This study identified 291 genes with differential expression in endometriotic lesions. The deregulation of the SPARC, MYC, MMP3, and IGFBP1 genes may be responsible for the loss of cellular homeostasis in endometriotic lesions. (Fertil Steril(R) 2010;93:1750-73. (C) 2010 by American Society for Reproductive Medicine.)

Polymorphisms of Lewis and Secretor genes are related to breast cancer and metastasis in axillary lymph nodes

ABH and Lewis antigen expression has been associated with cancer development and prognosis, tumor differentiation, and metastasis. Considering that invasive ductal breast carcinoma (IDC) presents multiple molecular alterations, the aim of the present study was to determine whether the polymorphism of ABO, Lewis, and Secretor genes, as well as ABO phenotyping, could be associated with tumor differentiation and lymph nodes metastasis. Seventy-six women with IDC and 78 healthy female blood donors were submitted to ABO phenotyping/genotyping and Lewis and Secretor genotyping. Phenotyping was performed by hemagglutination and genotyping by the polymerase chain reaction with sequence-specific primers. ABO, Lewis, and Secretor genes were classified by individual single nucleotide polymorphism at sites 59, 1067, 202, and 314 of the Lewis gene, 428 of the Secretor gene, and 261 (O1 allele), 526 (O2 and B allele), and 703 (B allele). No association was found between breast cancer and ABO antigen expression (P = 0.9323) or genotype (P = 0.9356). Lewis-negative genotype was associated with IDC (P = 0.0126) but not with anatomoclinical parameters. Nonsecretor genotype was associated with axillary lymph node metastasis (P = 0.0149). In conclusion, Lewis and Secretor genotyping could be useful to predict respectively breast cancer susceptibility and axillary lymph nodes metastasis.

Clinical Criteria as Predictive Factors of Response to Primary Hormone Therapy in Locally Advanced Breast Cancer

This study investigates the efficacy of clinical criteria in selecting patients for primary tamoxifen therapy. A total of 60 breast cancer patients with large primary tumors and unknown hormonal receptor status were subjected to primary hormone therapy. Inclusion criteria were age over 60 years old or menopausal status for at least 10 years and no clinical evidence of inflammatory disease and fast tumor growth. The objective response rate was 55%. There was a positive correlation between the lack of clinical response and axillary lymph node metastasis (p = 0.009). Patients with objective response had significantly improved disease-free (p = 0.045) and overall (p = 0.0002) survival over those who did not have response to hormonal therapy. In multivariate analysis, the clinical response to therapy was the most powerful prognostic factor. This analysis demonstrates that clinical criteria were very effective predictor of response to neo-adjuvant hormone therapy in large breast tumors for postmenopausal women. Response to therapy is the major prognostic factor in primary tamoxifen-treated breast cancer.

Serological testing for celiac disease in women with endometriosis. A pilot study

Purpose of Investigation: Celiac disease (CD) involves immunologically mediated intestinal damage with consequent micronutrient malabsorption and varied clinical manifestations, and there is a controversial association with infertility. The objective of the present study was to determine the presence of CD in a population of infertile women with endometriosis. Methods: A total of 120 women with a diagnosis of endometriosis confirmed by laparoscopy (study group) and 1,500 healthy female donors aged 18 to 45 years were tested for CD by the determination of IgA-transglutaminase antibody against human tissue transglutaminase (t-TGA) and anti-endomysium (anti-EMA) antibodies. Results: Nine of the 120 women in the study group were anti-tTGA positive and five of them were also anti-EMA positive. Four of these five patients were submitted to intestinal biopsy which revealed CD in three cases (2.5% prevalence). The overall CD prevalence among the population control group was 1:136 women (0.66%). Conclusion: This is the first study reporting the prevalence of CD among women with endometriosis, showing that CD is common in this population group (2.5%) and may be clinically relevant.

Differential effects of coffee on the risk of type 2 diabetes according to meal consumption in a French cohort of women: the E3N/EPIC cohort study

Background: Coffee consumption has been associated with a lower risk of diabetes, but little is known about the mechanisms responsible for this association, especially related to the time when coffee is consumed. Objective: We examined the long-term effect of coffee, globally and according to the accompanying meal, and of tea, chicory, and caffeine on type 2 diabetes risk. Design: This was a prospective cohort study including 69,532 French women, aged 41-72 y from the E3N/EPIC (Etude Epidemiologique aupres de Femmes de la Mutuelle Generale de l`Education Nationale/European Prospective Investigation into Cancer and Nutrition) cohort study, without diabetes at baseline. Food and drink intakes per meal were assessed by using a validated diet-history questionnaire in 1993-1995. Results: During a mean follow-up of 11 y, 1415 new cases of diabetes were identified. In multivariable Cox regression models, the hazard ratio in the highest category of coffee consumption [>= 3 cups (375 mL)/d] was 0.73 (95% CI: 0.61, 0.87; P for trend < 0.001), in comparison with no coffee consumption. This inverse association was restricted to coffee consumed at lunchtime (hazard ratio: 0.66; 95% CI: 0.57, 0.76) when comparing >1.1 cup (125 mL)/meal with no intake. At lunchtime, this inverse association was observed for both regular and decaffeinated coffee and for filtered and black coffee, with no effect of sweetening. Total caffeine intake was also associated with a statistically significantly lower risk of diabetes. Neither tea nor chicory consumption was associated with diabetes risk. Conclusions: Our data support an inverse association between coffee consumption and diabetes and suggest that the time of drinking coffee plays a distinct role in glucose metabolism. Am J Clin Nutr 2010; 91: 1002-12.

Study of the Discriminative Validity of the PHQ-9 and PHQ-2 in a Sample of Brazilian Women in the Context of Primary Health Care

PURPOSE. This study aimed to assess the discriminative validity of the Brazilian version of the Patient Health Questionnaire (PHQ-9) and of its reduced version (PHQ-2). DESIGN AND METHODS. The sample consisted of 177 women (60 cases of depression and 117 noncases). The SCID-IV was used as the gold standard. FINDINGS. For the PHQ-9, a cutoff score equal to or higher than 10 proved to be the most adequate for the screening of depression, whereas the best cutoff score for the PHQ-2 was found to lie between 3 and 4. PRACTICE IMPLICATIONS. The systematic use of these instruments in nursing and in the context of primary health care could favor the early detection of depression.

HIGH EXPRESSION OF CANCER TESTIS ANTIGENS MAGE-A, MAGE-C1/CT7, MAGE-C2/CT10, NY-ESO-1, AND GAGE IN ADVANCED SQUAMOUS CELL CARCINOMA OF THE LARYNX

Background. Despite diagnostic and therapeutic advances in head and neck cancer, the 5-year survival of patients with laryngeal cancer has not improved in the last 30 years. Several recent studies indicate that specific targets for immunotherapeutic approaches can be useful in the control of cancer. There is considerable interest in the expression of cancer testis antigens in human cancers since they may serve as the basis for an immunologic approach to therapy. Methods. We evaluated by immunohistochemical analysis the expression of cancer testis antigens MAGE-A4 (57B), MAGE-C1 (CT7-33), MAGE-A1 (MA454), MAGE-A3 (M3H67), MAGE-C2 (CT10.5), NY-ESO-1 (E978), and GAGE (GAGE) in squamous cell carcinoma (SCC) of the larynx. Results. A total of 63 cases (57 men and 6 women) of laryngeal SCC were available for this study. The findings were correlated with the clinical course and laboratory data. Expression of at least 1 cancer testis antigen was detected in 42 of 63 of the laryngeal SCCs (67%). In 34 of 42 of the positive cases (81%) there was simultaneous expression of >= 2 cancer testis antigens. There was significant correlation between antigen expression and advanced tumor stage (stage III/IV) in cases with reactivity to only 1 antibody (p = .01) as well as in the cases with reactivity to >= 2 primary antibodies (>= 2 mAbs, p = .04). There was no association between survival and expression of any of the analyzed antigens. Conclusions. We find a high incidence of cancer testis antigen expression in SCCs of the larynx, which was correlated with advanced clinical stage. Our data indicate that cancer testis antigens could be valuable vaccine targets in laryngeal tumors, especially in those with a worse prognosis. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 702-707, 2011

Knowledge and Practice of Prechewing/Prewarming Food by HIV-Infected Women

OBJECTIVE: HIV transmission has been associated with offering a child food prechewed by an HIV-infected caregiver. We assessed awareness of prechewing and oral prewarming of food by an adult before offering it to a child among HIV-infected pregnant women and clinical investigators in 3 Latin American countries. METHODS: HIV-infected pregnant women at 12 sites (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative Perinatal Longitudinal Study in Latin American Countries, a prospective cohort trial) in Argentina, Brazil, and Peru were administered a screening survey about prechewing/prewarming of infant foods and cautioned against these feeding practices. Survey responses were analyzed, overall, and stratified according to country. RESULTS: Of the 401 HIV-infected pregnant women interviewed, 34% had heard about prechewing (50% from Argentina, 32% from Brazil, and 36% from Peru), 23% knew someone who prechewed food for infants, and 4% had prechewed food in the past. Seventeen percent had heard about oral prewarming of food, 13% knew someone who prewarmed food for infants, and 3% had prewarmed food for an infant in the past. Women who reported knowing someone who prechewed were more likely to also know someone who prewarmed food (P < .0001). Few site investigators anticipated that their patients would be aware of these practices. CONCLUSIONS: Prechewing food, a potential risk factor for HIV transmission, and orally prewarming food, which has not been associated with HIV transmission but might expose a child to blood from an HIV-infected adult, are not uncommon practices in Latin America. Both practices should be further investigated. Site investigator responses underscore that health care providers could be missing information about cultural practices that patients may not report unless specifically asked. Pediatrics 2011;127:e1206-e1211