Resumo: Avaliar a prevalência de disfunções do assoalho pélvico após o tratamento de carcinoma invasor de colo uterino. Uma amostra de sessenta mulheres submetidas á histerectomia radical (n=20), radioterapia exclusiva (n=20) ou quimiorradiação (n=20) foram incluídas para análise. As funções de assoalho pélvico foram avaliadas por meio de questionários e avaliação física após, pelo menos, 6 meses do final do tratamento. A análise estatística realizada foram os testes de Mann-Whitney, kruskal-Wallis, Wilcoxon, Qui-quadrado quando apropriados. O p<0,05 foi considerado significativo. A idade variou de 28 a 75 anos (52,5 l 9,3 anos). O estádio clínico do tumor (FIGO) foi I em 25 casos (41,67%), II em 12 (20%), III em 22 (36,67%) and IV em 1 caso (1,67%). Os grupos foram semelhantes em relação a idade, paridade, menopausa e IMC. O comprimento vaginal foi menor em pacientes submetidas à radioterapia ou quimiorradiação quando comparadas com o grupo de histerectomia radical (5,5l1,9, 5,3l1,5 versus 7,4l1,1 cm, respectivamente; p<0,001). Não houve diferença em relação à incontinência urinária de esforço (p=0,56), urgência (p=0,44), urgeincontinência (p=0,54) e noctúria (p=0,53). Vida sexual ativa foi mais freqüente nas mulheres submetidas à cirurgia (90%) quando comparadas com o grupo da radioterapia (50%) e quimiorradiação (50%) (p=0,01). A dispareunia foi maior no grupo da radioterapia exclusiva, seguida da quimiorradiação e da histerectomia radical (p=0.021). O grupo da quimiorradiação apresentou maior freqüência evacuatória/dia (p<0.001) e a presença de diarréia foi menor no grupo da histerectomia radical (p=0.025), nos outros dois grupos foi semelhante. As disfunções do assoalho pélvico são comuns após o tratamento para carcinoma invasor de colo uterino. A radioterapia e a quimiorradiação são mais associadas às limitações... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This study was undertaken to evaluate the prevalence of pelvic floor dysfunction following treatment for invasive carcinoma of the cervix. Sixty patients submitted to radical hysterectomy (n=20), radiotherapy (n=20) or chemoradiation (n=20) were included for analysis. Pelvic floor function was assessed by questionnaires and physical examination at least 6 months after the treatment has finished. Main outcome measures were urinary, intestinal and sexual functions and vaginal length. Data of patients were collected prospectively. Statistical analysis was performed using oe2 , Mann- Whitney, Kruskal-Wallis and Wilcoxon as appropriate. P-value< 0.05 was significantly. The age of patients ranged from 28 to 75 years old (52.5 l 9.3 years). Tumor staging (FIGO) was I in 25 cases (41.67%), II in 12 (20%), III in 22 (36.67%) and IV in 1 case (1.67%). Vaginal length was shorter in the patients submitted to radiotherapy or chemoradiation compared to radical hysterectomy group (5.5l1.9, 5.3l1.5 versus 7.4l1.1 cm; p<0.001). There were no differences regarding stress incontinence (p=0.56), urgency (p=0.44), urgeincontinence(p=0.54) and nocturia (p=0.53). Active sexual life was significantly higher in women submitted to surgical treatment (p=0.01), and dyspareunia was higher in the group of radiotherapy (p=0.021). The bowel frequency was higher in group of patients submitted to chemoradiation (p=0.025). Pelvic floor dysfunctions are common after treatment for invasive cervical carcinoma. Radiotherapy and chemoradiaiton are more associated to a limitation in sexual activity and bowel dysfunction than surgery. / Orientador: Agnaldo Lopes da Silva-Filho / Coorientador: Paulo Traiman / Banca: Jorge Nahás Neto / Banca: Sérgio Augusto Triginelli / Mestre

Proteomic analysis of breast cancer tissue has proven difficult due to its inherent histological complexity. This pilot study presents preliminary evidence for the ability to differentiate adenoma and invasive carcinoma by measuring changes in proteomic profile of matched normal and disease tissues. A dual lysis buffer method was used to maximize protein extraction from each biopsy, proteins digested with trypsin, and the resulting peptides iTRAQ labeled. After combining, the peptide mixtures they were separated using preparative IEF followed by RP nanoHPLC. Following MALDI MS/MS and database searching, identified proteins were combined into a nonredundant list of 481 proteins with associated normal/tumor iTRAQ ratios for each patient. Proteins were categorized by location as blood, extracellular, and cellular, and the iTRAQ ratios were normalized to enable comparison between patients. Of those proteins significantly changed (upper or lower quartile) between matched normal and disease tissues, those from two invasive carcinoma patients had >50% in common with each other but <22% in common with an adenoma patient. In invasive carcinoma patients, several cellular and extracellular proteins that were significantly increased (Periostin, Small breast epithelial mucin) or decreased (Kinectin) have previously been associated with breast cancer, thereby supporting this approach for a larger disease-stage characterization effort.

Made available in DSpace on 2014-06-11T19:26:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-08-31Bitstream added on 2014-06-13T18:54:34Z : No. of bitstreams: 1 noronha_af_me_botfm.pdf: 252791 bytes, checksum: c5cc71429a0a70b1c137589b43b42506 (MD5) / Fundação para o Desenvolvimento Médico e Hospitalar (Famesp) / Avaliar a prevalência de disfunções do assoalho pélvico após o tratamento de carcinoma invasor de colo uterino. Uma amostra de sessenta mulheres submetidas á histerectomia radical (n=20), radioterapia exclusiva (n=20) ou quimiorradiação (n=20) foram incluídas para análise. As funções de assoalho pélvico foram avaliadas por meio de questionários e avaliação física após, pelo menos, 6 meses do final do tratamento. A análise estatística realizada foram os testes de Mann-Whitney, kruskal-Wallis, Wilcoxon, Qui-quadrado quando apropriados. O p<0,05 foi considerado significativo. A idade variou de 28 a 75 anos (52,5 l 9,3 anos). O estádio clínico do tumor (FIGO) foi I em 25 casos (41,67%), II em 12 (20%), III em 22 (36,67%) and IV em 1 caso (1,67%). Os grupos foram semelhantes em relação a idade, paridade, menopausa e IMC. O comprimento vaginal foi menor em pacientes submetidas à radioterapia ou quimiorradiação quando comparadas com o grupo de histerectomia radical (5,5l1,9, 5,3l1,5 versus 7,4l1,1 cm, respectivamente; p<0,001). Não houve diferença em relação à incontinência urinária de esforço (p=0,56), urgência (p=0,44), urgeincontinência (p=0,54) e noctúria (p=0,53). Vida sexual ativa foi mais freqüente nas mulheres submetidas à cirurgia (90%) quando comparadas com o grupo da radioterapia (50%) e quimiorradiação (50%) (p=0,01). A dispareunia foi maior no grupo da radioterapia exclusiva, seguida da quimiorradiação e da histerectomia radical (p=0.021). O grupo da quimiorradiação apresentou maior freqüência evacuatória/dia (p<0.001) e a presença de diarréia foi menor no grupo da histerectomia radical (p=0.025), nos outros dois grupos foi semelhante. As disfunções do assoalho pélvico são comuns após o tratamento para carcinoma invasor de colo uterino. A radioterapia e a quimiorradiação são mais associadas às limitações... / This study was undertaken to evaluate the prevalence of pelvic floor dysfunction following treatment for invasive carcinoma of the cervix. Sixty patients submitted to radical hysterectomy (n=20), radiotherapy (n=20) or chemoradiation (n=20) were included for analysis. Pelvic floor function was assessed by questionnaires and physical examination at least 6 months after the treatment has finished. Main outcome measures were urinary, intestinal and sexual functions and vaginal length. Data of patients were collected prospectively. Statistical analysis was performed using oe2 , Mann- Whitney, Kruskal-Wallis and Wilcoxon as appropriate. P-value< 0.05 was significantly. The age of patients ranged from 28 to 75 years old (52.5 l 9.3 years). Tumor staging (FIGO) was I in 25 cases (41.67%), II in 12 (20%), III in 22 (36.67%) and IV in 1 case (1.67%). Vaginal length was shorter in the patients submitted to radiotherapy or chemoradiation compared to radical hysterectomy group (5.5l1.9, 5.3l1.5 versus 7.4l1.1 cm; p<0.001). There were no differences regarding stress incontinence (p=0.56), urgency (p=0.44), urgeincontinence(p=0.54) and nocturia (p=0.53). Active sexual life was significantly higher in women submitted to surgical treatment (p=0.01), and dyspareunia was higher in the group of radiotherapy (p=0.021). The bowel frequency was higher in group of patients submitted to chemoradiation (p=0.025). Pelvic floor dysfunctions are common after treatment for invasive cervical carcinoma. Radiotherapy and chemoradiaiton are more associated to a limitation in sexual activity and bowel dysfunction than surgery.

Yes / Matched healthy and diseased tissues from breast cancer patients were analyzed by quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive ductal carcinoma (four patients), we identified protein alterations that correlated with breast cancer progression. Three 8-plex iTRAQ experiments generated an average of 826 protein identifications, of which 402 were common. After excluding those originating from blood, 59 proteins were significantly changed in tumor compared with normal tissues, with the majority associated with invasive carcinomas. Bioinformatics analysis identified relationships between proteins in this subset including roles in redox regulation, lipid transport, protein folding, and proteasomal degradation, with a substantial number increased in expression due to Myc oncogene activation. Three target proteins, cofilin-1 and p23 (increased in invasive carcinoma) and membrane copper amine oxidase 3 (decreased in invasive carcinoma), were subjected to further validation. All three were observed in phenotype-specific breast cancer cell lines, normal (nontransformed) breast cell lines, and primary breast epithelial cells by Western blotting, but only cofilin-1 and p23 were detected by multiple reaction monitoring mass spectrometry analysis. All three proteins were detected by both analytical approaches in matched tissue biopsies emulating the response observed with proteomics analysis. Tissue microarray analysis (361 patients) indicated cofilin-1 staining positively correlating with tumor grade and p23 staining with ER positive status; both therefore merit further investigation as potential biomarkers. / Cyprus Research Promotion Foundation, Yorkshire Cancer Research

O cÃncer do colo do Ãtero à um dos mais preocupantes problemas de saÃde pÃblica do planeta. SÃo esperados para 2013, no Brasil, 17.540 casos novos. Acredita-se atualmente que a maior parte dos cÃnceres cervicais se desenvolve a partir das neoplasias intraepiteliais cervicais. A aquisiÃÃo de propriedades invasivas dos tumores malignos està associada ao desequilÃbrio nas adesÃes intercelulares. As molÃculas de adesÃo tÃm papel fundamental nestas uniÃes e a caderina-E à uma das mais importantes. Està comprovada a sua presenÃa na membrana celular de tecidos epiteliais normais e foi demonstrado que esta proteÃna tem sua expressÃo diminuÃda na maioria dos tumores sÃlidos, o que favorece o processo de invasÃo. O objetivo, neste estudo, foi investigar a imunoexpressÃo da caderina-E nas Cervicites, nas LesÃes Intraepiteliais Escamosas (LIE) e no Carcinoma Invasivo do colo uterino. A amostra consistiu de 83 casos de biÃpsias e cones de colo do Ãtero obtidos dos arquivos do Departamento de Patologia e Medicina Legal da Universidade Federal do CearÃ, em 2007 e 2010, com os seguintes diagnÃsticos: Cervicite = 8 casos; LesÃo Intraepitelial Escamosa de Baixo Grau (LIEBG) = 24 casos; LesÃo Intraepitelial Escamosa de Alto Grau (LIEAG) = 28 casos; Carcinoma Invasor = 23 casos. A imunohistoquÃmica (IHQ) foi efetuada com o anticorpo monoclonal anti-caderina-E, tendo sido considerada positiva a presenÃa de expressÃo membranar, e negativa, a ausÃncia de expressÃo. O teste exato de Fisher foi utilizado para os cÃlculos das tabelas de contingencias. Os resultados da imunomarcaÃÃo foram: Cervicites = 1/8 (12%) negativos e 7/8 (88%) casos positivos para caderina-E; LIEBG = 7/24 (29%) casos negativos e 17/24 (71%) positivos; LIEAG = 7/28 (25%) negativos e 21/28 (75%) positivos; Carcinoma Invasor = 19/23 (83%) negativos e 4/23 (17%) positivos. A expressÃo negativa foi muito mais frequente nas LIEs (27%), comparadas com as Cervicites (12%) apesar de diferenÃa nÃo significante (p = 0,6657). Nas LIEs, uma maior perda da caderina-E foi notada nas cÃlulas menos diferenciadas do 1/3 basal da espessura epitelial. Finalmente, observou-se que a ausÃncia de expressÃo membranar da caderina-E foi muito mais frequente no carcinoma epidermÃide invasor do que nas lesÃes intraepiteliais escamosas do colo do Ãtero. Estes dados mostraram a importÃncia da caderina-E na carcinogÃnese do colo uterino, no entanto, muitos aspectos permanecem sem explicaÃÃo e novos estudos sÃo necessÃrios. / Cervical cancer is one of the most important public health problems around the world. About 17.540 new cases are expected, in Brazil, for 2013. Actually, itâs believed that the majority of cervical cancers begin with non invasive dysplastic lesions, the cervical intraepithelial neoplasias. The acquisition of invasive properties, in epithelial malignancies, is associated to the disruption of intercellular adhesions. The adhesion molecules play a pivotal role in these intercellular bindings and E-cadherin is considered one of the most important among them. In normal epithelial tissues its presence in cell membrane is recognized and it was shown that a down regulation of these proteins in the majority of solid tumors may contribute to facilitate the invasive process. The aim, of this research, was to investigate the E-cadherin immunoexpression in cervicitis, in SILs and in the invasive carcinomas of the uterine cervix. Samples specimens consisted of 83 cases of uterine cervical biopsies and conizations retrieved from the Department of Pathology and Forensic Medicine files of the Federal University of Cearà (Brazil) in 2007 and 2010, distributed, by diagnostic, as follows: Cervicitis = 8 cases; Low Squamous Intraepithelial Lesion (LSIL) = 24 cases; High Squamous Intraepithelial Lesion (HSIL) = 28 cases; and Invasive Carcinoma = 23 cases. Immunohistochemistry (IHC) was performed with the anti-E-cadherin monoclonal antibody and it was considered positive the membranar expression, and, negative, the absence of membranar expression. The Fisherâs exact test was the choice for the contingency tables calculations. The immunostaining results were: Cervicitis = (12%) negative and 7/8 (88%) positive cases to E-cadherin; LSILs = 7/24 (29%) negative cases and 17/24 (71%) positive; HSILs = 7/28 (25%) negative and 21/28 (75%) positive; Invasive Carcinoma = 19/23 (83%) negative and 4/23 (17%) positive. The negative expression was much more frequent in SILs (27%) when compared to cervicitis (12%), although no significant difference (p = 0,6657). In SILs, a bigger E-cadherin loss was noted in undifferentiated cells at the basal third of epithelial thickness. Finally it was shown that the absence of E-cadherin membranar expression was much more frequent in the uterine cervix invasive carcinoma when compared to LSILs and HSILs. These data showed the E-cadherin importance in cervical carcinogenesis, nonetheless, several aspects remain without explication and new researches are to be performed.