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- Endometrial Cancer Spheres Show Cancer Stem Cells Phenotype and Preference for Oxidative MetabolismPublication . Carvalho, MJ; Laranjo, M; Abrantes, AM; Casalta-Lopes, J; Sarmento-Santos, D; Costa, T; Serambeque, B; Almeida, N; Gonçalves, T; Mamede, C; Encarnação, J; Oliveira, R; Paiva, A; de Carvalho, R; Botelho, F; Oliveira, CThis study aimed to characterize endometrial cancer regarding cancer stem cells (CSC) markers, regulatory and differentiation pathways, tumorigenicity and glucose metabolism. Endometrial cancer cell line ECC1 was submitted to sphere forming protocols. The first spheres generation (ES1) was cultured in adherent conditions (G1). This procedure was repeated and was obtained generations of spheres (ES1, ES2 and ES3) and spheres-derived cells in adherent conditions (G1, G2 and G3). Populations were characterized regarding CD133, CD24, CD44, aldehyde dehydrogenase (ALDH), hormonal receptors, HER2, P53 and β-catenin, fluorine-18 fluorodeoxyglucose ([18F]FDG) uptake and metabolism by NMR spectroscopy. An heterotopic model evaluated differential tumor growth. The spheres self-renewal was higher in ES3. The putative CSC markers CD133, CD44 and ALDH expression were higher in spheres. The expression of estrogen receptor (ER)α and P53 decreased in spheres, ERβ and progesterone receptor had no significant changes and β-catenin showed a tendency to increase. There was a higher 18F-FDG uptake in spheres, which also showed a lower lactate production and an oxidative cytosol status. The tumorigenesis in vivo showed an earlier growth of tumours derived from ES3. Endometrial spheres presented self-renewal and differentiation capacity, expressed CSC markers and an undifferentiated phenotype, showing preference for oxidative metabolism.
- Risk factors for human papillomavirus infection among women in Portugal: the CLEOPATRE Portugal StudyPublication . Pista, A; de Oliveira, CF; Cunha, MJ; Paixao, MT; Real, OOBJECTIVE: To investigate demographic, socioeconomic, lifestyle, and medical factors that might predispose women to cervical human papillomavirus (HPV) infection. METHOD: A cross-sectional population-based study was performed. Women aged 18-64 years who attended selected obstetrics and gynecology or sexually transmitted disease (STD) clinics in mainland Portugal between February 2008 and March 2009 were recruited, according to an age-stratified sampling strategy. Liquid-based cytology samples were analyzed centrally for HPV genotype and for cytologic features. Univariate and multivariate logistic regression analyses identified risk factors for HPV infection. RESULTS: Among the 2326 women evaluated, the crude prevalence of HPV infection was 19.4%. Lifetime number of sexual partners was a strong predictor of HPV infection (odds ratio 5.44 for 5-10 partners versus 1 partner; P<0.001). Other risk factors were young age (particularly among women aged 20-24 years; P<0.001); country of birth other than mainland Portugal (P=0.002); education up to secondary school level (P=0.010); smoking history (≤ 10 years; P=0.004); and any STD in the past 12 months (P=0.052). CONCLUSION: Data from the present study may aid identification of women at increased risk of HPV infection and target prevention strategies. TRIAL REGISTRATION: National Commission of Data Protection (CNPD) registration number 5346/2007; Sanofi Pasteur MSD study number HPV-E05.
- Transobturator slings for female stress urinary incontinencePublication . Sousa, A; Jesus, A; Carvalho, M; Carvalho, G; Marques, J; Falcão, F; Torgal, IStress urinary incontinence affects about 20-40% of women. Treatment with transobturator mid-urethral slings is consensually accepted nowadays. The goal of this study was to evaluate the success rate and most frequent complications of surgical treatment with transobturator mid-urethral slings in stress urinary incontinence.
- Oxidative Stress, DNA, Cell Cycle/Cell Cycle Associated Proteins and Multidrug Resistance Proteins: Targets of Human Amniotic Membrane in Hepatocellular CarcinomaPublication . Mamede, AC; Guerra, S; Laranjo, M; Santos, K; Carvalho, MJ; Carvalheiro, T; Moura, P; Paiva, A; Abrantes, AM; Maia, CJ; Botelho, MFThe anticancer effects of human amniotic membrane (hAM) have been studied over the last decade. However, the action mechanisms responsible for these effects are not fully understood until now. Previously results reported by our team proved that hAM is able to induce cytotoxicity and cell death in hepatocellular carcinoma (HCC), a worldwide high incident and mortal cancer. Therefore, this experimental study aimed to investigate the cellular targets of hAM protein extracts (hAMPE) in HCC through in vitro studies. Our results showed that hAMPE is able to modify oxidative stress environment in all HCC cell lines, as well as its cell cycle. hAMPE differently targets deoxyribonucleic acid (DNA), P21, P53, β-catenin and multidrug resistance (MDR) proteins in HCC cell lines. In conclusion, hAMPE has several targets in HCC, being clear that the success of this treatment depends of a personalized therapy based on the biological and genetic characteristics of the tumor.
- Human Papillomavirus Type Distribution in Cervical Intraepithelial Neoplasia Grade 2/3 and Cervical Cancer in Portugal: A CLEOPATRE II StudyPublication . Pista, A; Oliveira, CF; Lopes, C; Cunha, MJ; CLEOPATRE Portugal Study GroupOBJECTIVE: Cervical cancer is the third most frequent cancer in women, worldwide and etiologically associated with infection by human papillomavirus (HPV). Following the results of the first epidemiologic population-based CLEOPATRE study in Portugal, it was important to understand the HPV type-specific distribution in women with cervical intraepithelial neoplasia (CIN) grades 2 and 3 and invasive cervical cancer (ICC). METHODS: This was an observational, multicenter, cross-sectional study with retrospective data collection. Between January 2008 and May 2009, paraffin-embedded samples of histologically confirmed cases of CIN2, CIN3, and ICC were collected from the 5 regional health administrations in mainland Portugal. Eligible samples were sent to 2 central laboratories for histological reassessment and HPV genotyping. Prevalence estimates were calculated together with 95% confidence intervals. RESULTS: A total of 582 samples, 177 cases of CIN2, 341 of CIN3, and 64 of ICC, were included. The mean age of participants was 41.8 years (range, 20-88 years). The overall HPV prevalence was 97.9% with a higher prevalence of high-risk genotypes, particularly HPV 16. Multiple infections were observed in 11.2% of the cases. Human papillomavirus prevalence was 95.5% in CIN2, 99.4% in CIN3, and 96.9% in ICC. The 8 more frequent genotypes in order of decreasing frequency were HPV 16, 31, 58, 33, 51, 52, 18, and 35 in CIN2 and HPV 16, 31, 33, 58, 52, 35, 18, and 51 in CIN3. In ICC cases, the 12 detected HPV genotypes were HPV 16, 18, 31, 33, 45, 51, 52, 53, 56, 58, 59, and 73. However, HPV 53 and 73 were always associated to other high-risk genotypes. Human papillomavirus types 31, 51, 52, 56, and 59 were detected in 1 case each. CONCLUSIONS: Human papillomavirus prevalence and patterns of type-specific HPV positivity were comparable with other studies. Current HPV vaccines should protect against HPV genotypes responsible for 77.4% of ICC in Portugal.
- Risk factors for human papilomavirus infection among women in Portugal: the CLEOPATRE Portugal StudyPublication . Pista, A; Oliveira, CF; Cunha, MJ; Paixão, MT; Real, O; CLEOPATRE Portugal Study GroupOBJECTIVE: Human papillomavirus (HPV) is responsible for a range of diseases, including cervical cancer. The primary objectives of the CLEOPATRE Portugal study were to estimate the overall and age-stratified prevalence of cervical HPV infection and to assess HPV prevalence and type-specific distribution by cytological results among women aged 18 to 64 years, who reside in mainland Portugal. MATERIALS AND METHODS: This cross-sectional population-based study recruited women aged 18 to 64 years, according to an age-stratified sampling strategy, who attended gynecology/obstetrics or sexually transmitted disease clinics across the 5 regional health administrations in mainland Portugal between 2008 and 2009. Liquid-based cytology samples were collected and analyzed centrally for HPV genotyping (clinical array HPV 2 assay) and cytology. Prevalence estimates were adjusted for age using 2007 Portuguese census data. RESULTS: A total of 2326 women were included in the study. The overall prevalence of HPV infection in the study was 19.4% (95% confidence interval, 17.8%-21.0%), with the highest prevalence in women aged 18 to 24 years. High-risk HPV types were detected in 76.5% of infections, of which 36.6% involved multiple types. The commonest high-risk type was HPV-16. At least 1 of the HPV types 6/11/16/18 was detected in 32.6% of infections. The HPV prevalence in normal cytology samples was 16.5%. There was a statistically significant association between high-risk infection and cytological abnormalities (P < 0.001). CONCLUSIONS: This is the first population-based study to quantify and describe cervical HPV infection in mainland Portugal. This study provides baseline data for future assessment of the impact of HPV vaccination programs.
- Classification of radical hysterectomy adopted by the Gynecological Cancer Group of the European Organization for Research and Treatment of CancerPublication . Mota, F; Vergote, I; Trimbos, JB; Amant, F; Siddiqui, N; Del Rio, A; Verheijen, R; Zola, PThe Piver classification of radical hysterectomy for the treatment of cervical cancer is outdated and misused. The Surgery Committee of the Gynecological Cancer Group of the European Organization for Research and Treatment of Cancer (EORTC) produced, approved, and adopted a revised classification. It is hoped that at least within the EORTC participating centers, a standardization of procedures is achieved. The clinical indications of the new classification are discussed.
- Impact of pelvic radiotherapy on female sexualityPublication . Rodrigues, AC; Teixeira, R; Teixeira, T; Conde, S; Soares, P; Torgal, IPURPOSE: To assess physical and psychological morbidity, sexual functioning and social and relationship satisfaction among women treated with pelvic radiotherapy. METHODS: Observational (case-control) study of 199 women: 98 submitted to pelvic radiotherapy for the treatment of uterine, rectal or anal cancers and 101 without a personal history of cancer and similar socio-demographic variables. These completed a socio-demographic and clinical questionnaire, and validated measures of psychological health (DASS: Lovibond and Lovibond in Behav Res Ther 33:353-343, 1995), sexual function (FSFI: Rosen et al. in J Sex Marital Ther 26:191-208, 2007), social support (ESSS: Ribeiro in Analise Psicologica 3:547-558, 1999) and relationship satisfaction (IMS: Hudson in The WALMYR assessment scales scoring manual 1992). RESULTS: Women submitted to pelvic irradiation reported a higher rate of adverse physical symptoms in the last month: fatigue 59 versus 25% (p < 0.001), lack of strength 42 versus 20% (p = 0.001), diarrhoea 24 versus 12% (p = 0.032), vaginal discharge 17 versus 7% (p = 0.024), skin erythema 9 versus 2% (p = 0.026). Levels of depression, anxiety and stress were higher among radiotherapy patients, but only reach statistical significance for the stress parameter (6.1 vs. 4.0, p = 0.012). Also these women reported lower scores of satisfaction with social support (57.2 vs. 62.2, p = 0.005) and sexual function (8.5 vs. 13.5, p = 0.049). No statistically significant differences occurred between the two groups regarding scores of relationship satisfaction (20.8 vs. 19.9, p = n.s.). CONCLUSIONS: Our results suggested that pelvic radiotherapy had a negative impact on female sexuality. Thus, interventions that would help to reduce this impact need to be designed and integrated into routine clinical practice.
- Angiomixoma agressivo da vulvaPublication . Jardim, O; Matos, R; Falcão, F; Dinis, M; Oliveira, CFAn unusual myxoid and vascular appearing neoplasm of the vulva, termed an Aggressive Angiomyxoma, is described in two cases report. The clinical presentation and recurrence pattern were typical for previously described neoplasms of the same cellular pattern. The histopathology, difficulties in determining the surgical margins, and the treatment of this tumor are discussed.
- Influence of normal mammary epithelium on breast cancer progression: the protective role of early pregnancyPublication . Martins, FC; Botelho, MF; Cabrita, AM; Oliveira, CFAIMS AND BACKGROUND: The microenvironment has a well recognized role in breast cancer progression. Despite different theories, the mechanism of early pregnancy protection in mammary carcinogenesis is unknown. Since pregnancy is responsible for mammary gland differentiation, we tested the hypothesis that differentiated mammary epithelial cells may inhibit breast cancer progression. In other words, the protective role of early pregnancy could be due to the inhibitory influences of the more differentiated mammary tissue. METHODS: In order to test our hypothesis, we used 30 female Balb/c nude mice and MCF-7 cells of breast adenocarcinoma. The female mice were divided into two test groups, group I (GI) and group II (GII), and a control group. In GII, the animals were submitted to epithelial removal in the left fourth inguinal mammary gland at 3 weeks of age. Both groups were given continuous hormonal treatment to simulate the pregnancy development of the mammary gland. Two million MCF-7 cells were then injected into the fourth inguinal mammary gland (GI) or in the respective cleared mammary fat pad (GII). Five weeks later the mice were sacrificed and their tumors removed. Tumor development rates and tumor volumes were determined and proliferation and apoptosis were evaluated by immunohistochemistry. RESULTS: Tumors of GII mice had a larger mean volume than those of GI mice (P = 0.001, Mann-Whitney U-test) and an apparent increase in proliferation, demonstrated by a higher staining intensity for proliferating cell nuclear antigen (PCNA). As tumors presented caspase 8 staining, there may be apoptotic activation involved in cell death, mainly through an extrinsic pathway. CONCLUSIONS: These results suggest that a differentiated intact mammary gland may have an inhibitory influence on mammary tumor growth in mice.