Thesis (Ph.D.)--University of Rochester. School of Medicine and Dentistry. Dept. of Pathology and Laboratory Medicine, 2008. ; The growing elderly population in the United States has led to a greater number of bladder cancer patients and bladder cancer deaths in the past several years. Mitogenic signaling pathways, specifically the receptor tyrosine kinase erbB2-mediated pathway, are misregulated in bladder cancer, leading to a greater replicative potential in cells that overexpress such mediators. Since erbB2 has been shown to be overexpressed in nearly 50% of bladder cancers, a mouse model of bladder cancer was created to overexpress erbB2 spatially and temporally. While erbB2 RNA expression was induced in this mouse model and papillary growths in the bladder were noted, erbB2 overexpression alone seemed insufficient for bladder tumorigenesis. It may be that additional mitogenic, cell cycle regulatory, and apoptotic pathways need to be involved. Several different animal models of bladder cancer have been utilized in the past four decades, although none of them have been able to reliably detect, measure, and monitor tumors in vivo, instead relying on serial sacrifice. To eliminate the need for such cumbersome experiments...

Mutations on TP53 gene are common in human cancer but not in cervical cancer where they are rarely found and the inactivation and degradation of p53 protein are attributed to the action of E6 viral oncogene from high risk human papillomavirus (HPV). Analysis of cervical cancer cell lines suggests that HPV negative samples shows mutation on TP53, but clinical approaches didn t confirmed this hypothesis. However, in most TP53 mutations studies on cervical cancer, only the exons 5 to 8 were analyzed. Approximately 90% of mutations described are on this region. Recent studies on several cancer suggests that mutation frequency in the other exons must be considered. The aim of this work was to verify whether mutations on coding and non-coding regions occur in cancer tissue from cervical cancer in patients from Rio Grande do Norte using Denaturing Gradient Gel Electrophoresis (DGGE) as screening tool. Exons 8 to 11 were analyzed including some introns from 80 tumor samples and 8 peripheral blood samples from healthy women. DNA were submitted to PCR using primers with GC clamp on the end of one of them. The results were observed for each region after DGGE and silver staining. It was observed no amplified fragment with different migration profile from those obtained from DNA of peripheral blood. These results agree with those from literature where TP53 mutations in cervical cancer have been described in a very low frequency; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; As mutações no TP53 são frequentes nos cânceres humanos...

Introduction: Body composition modification, mainly the increase in total body fat, which is related to a number of illnesses, is an important public health problem, is quite prevalent in breast cancer patents and is directly associated with a negative prognosis for the illness. Objective: To evaluate the body composition, of total body fat and its distribution and lipid profile of women recently diagnosed with breast cancer, at two referral centers in Goiânia, Goiás. Methodology: (Article 1) A cross-sectional, cohort nested study. (Article 2). A case-control study, with 1:1 pairing, carried out in Goiânia, Goiás, Brazil. The data were collected through interviews based on questionnaire, with 62 women, a socio-demographic characterization and an evaluation of body composition using anthropometry including skinfolds (SF) and circumferences, bioelectrical impedance analysis (BIA) and ultrasonography (USG), besides the evaluation of lipid profile. Were carried an data tabulation (Excel/2003) and analysis (SPSS program, version 8.0) and (STATA, Intercooled Stata 8) and were used descriptive statistics. Was used in the data analyses: the Kolmogorov-Smirnov test, ??t?? test, chi-square for tendency, (Mann-Whitney U), Pearson??s chi-square...

O câncer de mama é o segundo tipo de câncer mais frequente no mundo e o mais comum entre as mulheres, representando cerca de 22% dos casos novos a cada ano. Considerando que a maioria dos casos de câncer de mama ainda é diagnosticada em estádios avançados da doença, existe grande possibilidade de ocorrência de comprometimento de linfonodos regionais e o desenvolvimento de metástases à distância, ou seja, a disseminação da doença para outros órgãos e tecidos. Diante disso, o presente estudo teve como objetivos verificar e correlacionar a eficácia adaptativa e o funcionamento global de mulheres com metástase de câncer de mama. Participaram deste estudo seis mulheres com metástase de câncer de mama, atendidas no Setor de Mastologia Maligna do Hospital de Clínicas da Universidade Federal de Uberlândia (HC/UFU). Os instrumentos utilizados foram: a Entrevista Clínica Preventiva, a Escala Diagnóstica Adaptativa Operacionalizada (EDAO), em suas duas propostas de avaliação, EDAO e EDAO/R, bem como a Escala de Avaliação Global do Funcionamento (AGF). Em relação à classificação da eficácia adaptativa das participantes deste estudo, os resultados mostraram que Gérbera, Tulipa e Gardênia apresentaram adaptação não eficaz moderada...

A glândula próstata pode ser acometida por várias patologias. Dentre elas o câncer de próstata é a 4a causa de morte em homens com idade superior a 50 anos. Apesar da etiologia desta doença não ser bem compreendida, as alterações genéticas e a presença de agentes infecciosos têm sido sugeridas como associadas ao desenvolvimento desse câncer. Uma das alterações genéticas mais freqüentes nos cânceres são as relacionadas ao gene supressor de tumor TP53, responsável pelo controle do ciclo celular e apoptose. No início da década de 90, vários trabalhos também surgiram na tentativa de estabelecer relação entre a infecção pelo vírus do papiloma humano (HPV) e o câncer de próstata. Dentro deste contexto, este trabalho teve como objetivos avaliar a prevalência do HPV, analisar o polimorfismo Arg72Pro, associar este polimorfismo à presença do HPV e rastrear por mutações nos exons de 5 a 8 do gene TP53 em pacientes apresentando câncer de próstata. Foram analisados 36 tecidos prostáticos sendo estes provenientes de adenocarcinoma, HPB e NIP e sangues periféricos de alguns desses pacientes bem como de um grupo de homens escolhidos aleatoriamente na população. As técnicas utilizadas para detecção e tipagem do HPV foram a PCR e a PCR nested. Já para a análise do polimorfismo Arg72Pro e para o rastreamento de mutações foram utilizadas as técnicas de PCR e LIS-SSCP. Não houve diferenças das freqüências do polimorfismo Arg72Pro entre os tecidos com HPB e CaP (p=0...

O câncer de próstata é a segunda causa de óbitos por câncer em homens, sendo superado apenas pelo câncer de pulmão. A ocorrência estimada é de 51 casos novos para cada 100 mil homens por ano para este tipo de câncer. O aumento observado nas taxas de incidência pode ser parcialmente justificado pela evolução dos métodos diagnósticos, pela melhoria na qualidade dos sistemas de informação do país e pelo aumento na expectativa de vida do brasileiro. A identificação de novos antígenos ou genes específicos do câncer de próstata pode prover novos biomarcadores e também fornecer instrumentos para o desenvolvimento de novas modalidades de tratamento. A tecnologia de Phage Display é capaz de selecionar peptídeos com diversas finalidades, como mimetizar antígenos reconhecidos por anticorpos. Peptídeos selecionados por esta técnica são potenciais marcadores tumorais para o diagnóstico do câncer de próstata. Por meio desta metodologia pode ser possível identificar proteínas capazes de detectar a resposta imune contra o tumor mais precocemente do que os métodos tradicionais, predizer o estadio atual do tumor, além de permitir o desenvolvimento de tratamentos mais eficientes. Pela imunização de galos SPF (livre de patógenos específicos) com proteínas totais de tecidos tumorais da próstata...

O conceito de crescimento pós-traumático (posttraumatic growth) se refere, basicamente, às transformações psicológicas positivas desencadeadas em função da tentativa de adaptação às novas circunstâncias implementadas por um evento traumático. Trata-se de um processo que envolve a interação de uma variedade de elementos, uma vez que as referidas transformações podem ser verificadas em diferentes domínios. O presente estudo tem como objetivo geral desenvolver uma revisão sistemática de publicações científicas dedicadas à exploração do crescimento pós-traumático, em mulheres acometidas por câncer de mama. O material foi localizado por meio de buscas eletrônicas em cinco bases de dados distintas – PsycINFO, MedLine, LILACS, SciELO-Brasil e PePsic – a partir do cruzamento dos termos “crescimento pós-traumático” (posttraumatic growth) e “câncer de mama” (breast cancer). As referências localizadas foram selecionadas em função de critérios de inclusão específicos. As referências selecionadas foram, então, recuperadas na íntegra e submetidas à avaliação em função de um conjunto de dimensões de análise. Apenas 31 das 74 referências localizadas foram selecionadas. Em linhas gerais...

Lung cancer is a major chronic disease responsible for the highest mortality rate, among other types of cancer, and represents 29% of all deaths in Canada. The clinical diagnosis of lung carcinoma still requires a standard diagnostic approach, as there are no symptoms in its early stage. Therefore, it is usually diagnosed at a later stage, when the survival rate is low. With the recent advancement in molecular biology and biotechnology, a molecular biomarker approach for the diagnosis of early lung cancer seems to be a potential option. In this study, we aimed to investigate and standardize a promising Lung ,Cancer Biomarker by studying the aberrant methylation of two tumour suppressor genes, namely RASSFIA and RAR-B, and the miRNA profiling of four . commonly deregulated miRNA (miR-199a-3p, miR-182, miR-lOO and miR-221). Four lung cancer cell lines were used (two SCLC and two NSCLC), with comparisons being made with normal lung cell lines. Our results, we found that none of these genes were methylated. We then evaluated TP53, and found the promoter of this gene to be methylated in the cancer cell lines, as compared to the normal cell lines, indicating gene inactivation. We carried out miRNA profiling of the cancer cell lines and reported that 80 miRNAs are deregulated in lung cancer cell lines as compared to the normal cell lines. Our study was the first of its kind to indicate that hsa-mir-4301...

BACKGROUND: X chromosome inactivation, which silences gene expression from one of the two X chromosomes in females, is usually random. Skewed X inactivation has been implicated in both the expression and the suppression of X-linked disease phenotypes and has been reported to occur more frequently in breast and ovarian cancer patients, including BRCA1 or BRCA2 mutation carriers, than in control subjects. METHODS: We assessed the pattern of X chromosome inactivation using methylation-specific polymerase chain reaction amplification of the exon 1 microsatellite region of the X-linked androgen receptor (AR) gene in DNA from blood samples obtained from control subjects without a personal history of breast or ovarian cancer (n = 735), ovarian cancer patients (n = 313), familial breast cancer patients who did not carry mutations in BRCA1 or BRCA2 (n = 235), and affected and unaffected carriers of mutations in BRCA1 (n = 260) or BRCA2 (n = 63). We defined the pattern of X chromosome inactivation as skewed when the same X chromosome was active in at least 90% of cells. The association between skewed X inactivation and disease and/or BRCA mutation status was assessed by logistic regression analysis. The association between skewed X inactivation and age at cancer diagnosis was assessed by Cox proportional hazards regression analysis. All statistical tests were two-sided. RESULTS: The age-adjusted frequency of skewed X inactivation was not statistically significantly higher in ovarian cancer or familial breast cancer case subjects compared with control subjects. Skewed X inactivation was higher in BRCA1 mutation carriers than in control subjects (odds ratio [OR] = 2.7...

Previous studies have demonstrated an increased risk of breast cancer among patients with systemic sclerosis (scleroderma). To describe the clinical characteristics of 21 patients with both systemic sclerosis and breast cancer, and compare their risk factors to female scleroderma patients without breast cancer, in a population-based cohort study of South Australia. Subjects with scleroderma and breast cancer were identified from the South Australian Scleroderma Register with cross-linking to the South Australian Cancer Registry, last updated to the end of December 2005. Clinical information was obtained from standardised self-administered questionnaires and case note reviews. Odds ratios for the risk factors for breast cancer in scleroderma were determined, and clinical variables were analysed using chi square, Fisher’s exact, Mann–Whitney and t tests. At the end of December 2005 there were a total of 389 female patients with scleroderma. Of these, 21 (5.4%) had been diagnosed with breast cancer. The mean age of onset of scleroderma was 43.5 years, and the mean age of breast cancer was 60.5 years in those with scleroderma and breast cancer. The majority (71.4%) had limited scleroderma, with anti-centromere antibody being the most prevalent serological abnormality. In 16 (76%) patients the diagnosis of breast cancer occurred on an average of 22.3 years after the onset of their first scleroderma symptom. When compared to 48 controls...

BACKGROUND: National cancer survival statistics are available for the total Australian population but not Indigenous Australians, although their cancer mortality rates are known to be higher than those of other Australians. We aimed to validate analysis methods and report cancer survival rates for Indigenous Australians as the basis for regular national reporting. METHODS: We used national cancer registrations data to calculate all-cancer and site-specific relative survival for Indigenous Australians (compared with non-Indigenous Australians) diagnosed in 2001-2005. Because of limited availability of Indigenous life tables, we validated and used cause-specific survival (rather than relative survival) for proportional hazards regression to analyze time trends and regional variation in all-cancer survival between 1991 and 2005. RESULTS: Survival was lower for Indigenous than non-Indigenous Australians for all cancers combined and for many cancer sites. The excess mortality of Indigenous people with cancer was restricted to the first three years after diagnosis, and greatest in the first year. Survival was lower for rural and remote than urban residents; this disparity was much greater for Indigenous people. Survival improved between 1991 and 2005 for non-Indigenous people (mortality decreased by 28%)...

El cáncer de mama acostumbra a generar sentimientos de miedo, tristeza y negación en la mujer y en los familiares. El objetivo fue analizar el comportamiento de la familia frente al diagnóstico de cáncer de mama. Estudio descriptivo con 15 familiares de mujeres mastectomizadas. Datos colectados a través de entrevistas semi-estructuradas y organizados para el análisis de contenido. El miedo estuvo presente entre los familiares durante el descubrimiento del cáncer y frente a la noticia de la cirugía. Percibimos deficiencias en las orientaciones a los familiares, muchas veces dejados de lado en el tratamiento. Estos manifestaron, generalmente, comportamientos ineficaces. El cáncer de mama y la consiguiente mastectomía ocasionan impacto en la familia, extendiéndose a los amigos.; O câncer de mama costuma gerar sentimentos de medo, tristeza e negação na mulher, e nos familiares. Objetivamos conhecer os comportamentos de familiares de mulheres mastectomizadas frente al diagnóstico de câncer de mama; verificar os mecanismos de enfrentamento utilizados pelos mesmos; e identificar a contribuição da família na recuperação da mulher. Estudo exploratório, com abordagem qualitativa, realizado com 15 familiares de mulheres mastectomizadas. Dados coletados através de entrevista semiestruturada e organizados pela análise de conteúdo. O medo esteve presente entre os familiares...

RESUMEN: La extensión linfática es el factor pronóstico más importante en el momento del diagnóstico del cáncer de mama. La Biopsia Selectiva del Ganglio Centinela (BSGC) es el procedimiento actualmente indicado para la estadificación regional de las pacientes con cáncer de mama precoz. La BSGC permite una estadificación más exacta que la linfadenectomía axilar tradicional (LDNA), gracias a la identificación de drenajes extra-axilares y de micrometástasis en el GC, de modo que el manejo terapeútico posterior de las pacientes ha de ser más acertado y la evolución clínica mejor. El objetivo de este trabajo es evaluar la eficiencia y seguridad de la aplicación clínica de la BSGC en las pacientes con cáncer de mama, perfilando la metodología óptima en cuanto al radiotrazador y la vía de administración, y analizando la indicación en situaciones clínicas especiales: carcinoma in situ, múltiple, o cirugía mamaria previa. Se estudian los primeros 600 procedimientos de BSGC realizados en fase clínica, a 591 pacientes con cáncer de mama estadio I y II. La eficiencia de detección gammagráfica e intraoperatoria del GC fue 94,5% y 90,5% respectivamente. El procedimiento de BSGC evita una LDNA innecesaria en el 68...

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Biologia Celular e do Desenvolvimento, Florianópolis, 2014.; Introdução: O câncer de mama possui etiologia variada, sendo influenciada tanto por fatores genéticos quanto por fatores ambientais. Dentro do contexto genético, o papel de genes que codificam moléculas do sistema imunológico tem sido alvo de interesse pela importância que esse sistema possui para o desenvolvimento do processo tumoral. A Interleucina-18 é uma importante citocina pró-inflamatória e que possui indicações como possível alvo-terapêutico. Possui polimorfismos de um único nucleotídeo localizados na região promotora do gene e que possuem atividade funcional. As células Natural Killer (NK) fazem parte da resposta imune inata, sendo a primeira linha de defesa do organismo contra vírus, bactérias e tumores. Estas células induzem a morte da célula-alvo quando não há o reconhecimento das moléculas de antígenos leucocitários humanos (HLA) de classe I, através de seus receptores, chamados Killer cell Immunoglobulin-like. Receptor (KIR) ou os receptores NKG2D. Vários estudos demonstram o envolvimento dos genes que codificam receptores de células NK na patogênese do câncer. Objetivo: Avaliação do papel de polimorfismos em genes envolvidos na regulação da atividade das células NK e o desenvolvimento do câncer de mama em pacientes do Estado de Santa Catarina. Resultados: A presença dos genótipos variantes dos polimorfismos IL18 -607 (C/A) [rs1946518] e IL18 -137 (G/C) [rs187238] no presente estudo apresentou um risco significativo para o desenvolvimento do câncer de mama...

Curcumin is a component of the Indian spice turmeric that has shown anti-cancer activity across a range of models. This includes prostate cancer, the most commonly diagnosed cancer in Australia. While much of the current literature relates to epithelial cells, there is no information regarding curcumin activity or resistance in prostate fibroblasts. With curcumin recently entering clinical trials for prostate cancer and being increasingly used as a dietary supplement, it is critical to gain an understanding of curcumin action and potential resistance in these cells, given their reported contribution to cancer progression. Furthermore, with drug resistance being a major setback to cancer therapy, it is also important to investigate curcumin-based combination strategies to enhance efficacy and avoid the development of resistance. The aims of this thesis were therefore to comparatively investigate mechanisms of curcumin action in prostate cancer cells and fibroblasts, to explore the potential for curcumin resistance to occur in prostate fibroblasts and to examine the ability of curcumin to re-sensitise prostate cancers resistant to drozitumab, a monoclonal antibody against death receptor 5 (DR5). Curcumin inhibited prostate cancer cell and fibroblast viability...

Breast cancer in males is much rare than in females so in practice, male breast cancer treatment is likely to follow the guidelines developed for female breast cancer patients. The objective of this study is to compare the characteristics and treatment pattern of male breast cancer patients with comparable subgroups of female breast cancer patients using data submitted to the National Breast Cancer Audit. This is a retrospective analysis of 151 male breast cancers diagnosed and treated between 2000 and 2008. Most of the male early breast cancer cases in this group were symptomatic ones in men aged >50 years with one invasive tumour. There was a similar proportion of lymph node positive cancer among males and females, although male breast cancer was more likely to be unifocal (P=0.007) and oestrogen receptor positive (P=0.001). Male breast cancer patients almost always underwent mastectomy and a significant proportion of them (11%) received no surgical treatment. There were no differences in axillary surgery although males were more likely to undergo a level 2 axillary surgery and less likely to have sentinel node biopsy. Male patients were significantly less likely to undergo radiotherapy, chemotherapy or hormonal therapy for oestrogen receptor positive tumours.While the female oriented treatment guidelines are available...

INTRODUCTION: The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) is a multidisciplinary, collaborative framework for the investigation of familial breast cancer. Based in Australia, the primary aim of kConFab is to facilitate high-quality research by amassing a large and comprehensive resource of epidemiological and clinical data with biospecimens from individuals at high risk of breast and/or ovarian cancer, and from their close relatives. METHODS: Epidemiological, family history and lifestyle data, as well as biospecimens, are collected from multiple-case breast cancer families ascertained through family cancer clinics in Australia and New Zealand. We used the Tyrer-Cuzick algorithms to assess the prospective risk of breast cancer in women in the kConFab cohort who were unaffected with breast cancer at the time of enrolment in the study. RESULTS: Of kConFab's first 822 families, 518 families had multiple cases of female breast cancer alone, 239 had cases of female breast and ovarian cancer, 37 had cases of female and male breast cancer, and 14 had both ovarian cancer as well as male and female breast cancer. Data are currently held for 11,422 people and germline DNAs for 7,389. Among the 812 families with at least one germline sample collected...

This study aimed to search available evidences in literature about social support to families of children with cancer. An integrative review was elaborated and the articles were searched in PUBMED, WEB of SCIENCE, CINAHL, PsycINFO and LILACS, using the key words: social support, cancer, child and family, between 1996 and 2006. Fifteen articles were selected and the analysis of these publications allowed for the identification of three themes: social support and the trajectory of cancer, social support to healthy siblings and social support to fathers and mothers of children with cancer. Data indicated a lack of consensus among researchers about the use of the term social support and that there is a need for greater methodological rigor in the conduction of these studies. Acknowledging the clients' support needs is important to plan nursing care and guide research development, whose results can be used in practice.; La finalidad de este estudio fue buscar las evidencias que se encontraban disponibles sobre el apoyo social a familias de niños con cáncer. Se realizó una revisión integradora y los artículos fueron buscados en las bases de datos PUBMED, WEB of SCIENCE, CINAHL, PsycINFO y LILACS, con las palabras clave: social support...

O diagnóstico de câncer de mama e seu tratamento afetam a condição física, social e emocional da mulher. Frente aos eventos estressores desencadeados pelo adoecimento, a mulher faz uso de estratégias de enfrentamento específicas para cada fase da doença, tratamento e reabilitação, com o intuito de se adaptar às novas situações e contexto de vida. As pesquisas que discorrem sobre o enfrentamento em câncer de mama estão concentradas no que se refere aos períodos de diagnóstico e tratamento, sendo escassas quanto ao período da reabilitação (pós-tratamento). Nesse sentido, o presente estudo tem como objetivo investigar o processo de enfrentamento nas mulheres com câncer de mama durante o período pós-tratamento. A aproximação ao objeto de estudo deu-se através do referencial teórico do Enfrentamento (coping). Foram investigadas 16 mulheres com câncer de mama, com tempo de diagnóstico variando entre 1 e 4 anos, já submetidas à mastectomia (total ou parcial), radioterapia e/ou quimioterapia, e que estavam sendo atendidas em um programa de reabilitação física e psicossocial. Para tal, foram utilizados três instrumentos, a saber: 1) Entrevista com Roteiro Estruturado, 2) Escala de Modos de Enfrentamento de Problemas (EMEP) e 3) Inventário de Sintomas de Stress para Adultos de Lipp (ISSL). Os dados foram tratados sob a abordagem metodológica quanti-qualitativa. Os resultados indicaram a presença de estressores físicos...

É complexa a interrelação entre câncer, desnutrição e imunidade. A desnutrição nos pacientes hospitalizados que se submeteram ao tratamento cirúrgico atinge elevados Índices, o que contribui para aumentar as complicações pós-operatórias, permanência hospitalar e consequentemente aumentar o custo com o tratamento deste doente. O objetivo deste estudo foi reverter a desnutrição em pacientes com câncer de cabeça e pescoço que se submeteram ao tratamento antineoplãsico, obtendo um diagnóstico nutricional precoce e instituindo uma terapêutica nutricional específica. 0 total de 28 casos com câncer de cabeça e pescoço foram submetidos à avaliação nutricional global (ANG), ao suporte nutricional enteral (SNE) e foram monitorados durante sua internação. Foi instituído a terapêutica nutricional e a avaliação final foi através dos parâmetros: clínicos, subjetivos, bioquímicos, imunológicos e índices compostos, segundo as seguintes medidas: percentual de perda de peso recente (%PP), circunferência muscular do braço (CMB), prega cutânea do tríceps (PCT), perímetro do braço {PB) linfocítometria (LINF), proteínas totais (PT), albumina (ALB), transferrina (TRANSF), balanço nitrogenado (EN), índice creatinina altura (ICA) e gasto energético total (GET). As medidas aferidas de BN...