Characterization of cancer/testis antigen MAGE-A11 for immunotherapy of prostate cancer

Les antigènes testiculaires du cancer sont des cibles idéales pour l’immunothérapie du cancer car ce sont des protéines immunogéniques dont l’expression est restreinte aux cellules germinales et au cancer. Le but de cette étude est d’évaluer le potentiel de MAGE-A11, un antigène testiculaire du cancer, comme cible pour développer un vaccin contre le cancer de la prostate. Pour ce faire, l’anticorps monoclonal 5C4 qui a la capacité de reconnaître la présence de MAGE-A11 dans les tissus fixés et inclus en paraffine a été produit. De plus, l’expression de MAGE-A11 a été analysée sur plusieurs lignées de cellules cancéreuses. Il a été démontré que MAGE-A11 est exprimé dans plusieurs types de cancers notamment dans le cancer du côlon et du cerveau. Finalement, nous avons identifié trois épitopes du CMH classe II HLA-DR1 dans la protéine MAGE-A11 confirmant ainsi l’immunogénicité de cet antigène et son potentiel comme cible pour l’immunothérapie du cancer.

The regulation of cancer cell invasive behaviour by Chloride Interacellular Channel 3 (CLIC3) and Transglutaminasae 2

A study into the role of secreted CLIC3 in tumour cell invasion. The initiation and progression of cancers is thought to be linked to their relationship with a population of activated fibroblasts, which are associated with tumours. I have used an organotypic approach, in which plugs of collagen I are preconditioned with fibroblastic cells, to characterise the mechanisms through which carcinoma-associated fibroblasts (CAFs) influence the invasive behaviour of tumour cells. I have found that immortalised cancer-associated fibroblasts (iCAFs) support increased invasiveness of cancer cells, and that this is associated with the ability of CAFs to increase the fibrillar collagen content of the extracellular matrix (ECM). To gain mechanistic insight into this phenomenon, an in-depth SILAC-based mass proteomic analysis was conducted, which allowed quantitative comparison of the proteomes of iCAFs and immortalised normal fibroblast (iNFs) controls. Chloride Intracellular Channel Protein 3 (CLIC3) was one of the most significantly upregulated components of the iCAF proteome. Knockdown of CLIC3 in iCAFs reduced the ability of these cells to remodel the ECM and to support tumour cell invasion through organotypic plugs. A series of experiments, including proteomic analysis of cell culture medium that had been preconditioned by iCAFs, indicated that CLIC3 itself was a component of the iCAF secretome that was responsible for the ability of iCAFs to drive tumour cell invasiveness. Moreover, addition of soluble recombinant CLIC3 (rCLIC3) was sufficient to drive the extension of invasive pseudopods in cancer cell lines, and to promote disruption of the basement membrane in a 3D in vitro model of the ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition. My investigation into the mechanism through which extracellular CLIC3 drives tumour cell invasiveness led me to focus on the relationship between CLIC3 and the ECM modifying enzyme, transglutaminase-2 (TG2). Through this, I have found that TG2 physically associates with CLIC3 and that TG2 is necessary for CLIC3 to drive tumour cell invasiveness. These data identifying CLIC3 as a key pro-invasive factor, which is secreted by CAFs, provides an unprecedented mechanism through which the stroma may drive cancer progression.

Association of TNF-α Gene Variants With Clinical Manifestation of Cystic Fibrosis Patients of Iranian Azeri Turkish Ethnicity

Background: Cystic fibrosis (CF), a life-limiting autosomal recessive disorder, is considered a monogenic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. According to several studies, mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene alone is insufficient to predict the phenotypic manifestations observed in cystic fibrosis (CF) patients. In addition, some patients with a milder CF phenotype do not carry any pathogenic mutation. Tumor Necrosis Factor-alpha (TNF-α) contributes to the pathophysiology of CF by causing cachexia. There is a reverse association between TNF-α concentration in patient's sputum and their pulmonary function. Objectives: To assess the effect of non-CFTR genes on the clinical phenotype of CF, two polymorphic sites (-1031T/C and -308G/A) of the TNF-α gene, as a modifier, were studied. Patients and Methods: Focusing on the lung and gastrointestinal involvement as well as the poor growth, we first investigated the role of TNF-α gene in the clinical manifestation of CF. Furthermore, based on the hypothesis that the cumulative effect of specific alleles of multiple CF modifier genes, such as TNF-α, may create the final phenotype, we also investigated the potential role of TNF-α in non-classic CF patients without a known pathogenic mutation. In all, 80 CF patients and 157 healthy control subjects of Azeri Turkish ethnicity were studied by the PCR–RFLP method. The chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis. Results: The allele and genotype distribution of the investigated polymorphisms, and their associated haplotypes were similar in all groups. Conclusions: There was no evidence that supported the association of TNF-α gene polymorphisms with non-classic CF disease or the clinical presentation of classic CF.

Subject response rates in case-control studies of cancer : time trends, study design determinants, and quality of reporting

Objectifs: Examiner les tendances temporelles, les déterminants en lien avec le design des études et la qualité des taux de réponse rapportés dans des études cas-témoins sur le cancer publiées lors des 30 dernières années. Méthodes: Une revue des études cas-témoins sur le cancer a été menée. Les critères d'inclusion étaient la publication (i) dans l’un de 15 grands périodiques ciblés et (ii) lors de quatre périodes de publication (1984-1986, 1995, 2005 et 2013) couvrant trois décennies. 370 études ont été sélectionnées et examinées. La méthodologie en lien avec le recrutement des sujets et la collecte de données, les caractéristiques de la population, les taux de participation et les raisons de la non-participation ont été extraites de ces études. Des statistiques descriptives ont été utilisées pour résumer la qualité des taux de réponse rapportés (en fonction de la quantité d’information disponible), les tendances temporelles et les déterminants des taux de réponse; des modèles de régression linéaire ont été utilisés pour analyser les tendances temporelles et les déterminants des taux de participation. Résultats: Dans l'ensemble, les qualités des taux de réponse rapportés et des raisons de non-participation étaient très faible, particulièrement chez les témoins. La participation a diminué au cours des 30 dernières années, et cette baisse est plus marquée dans les études menées après 2000. Lorsque l'on compare les taux de réponse dans les études récentes a ceux des études menées au cours de 1971 à 1980, il y a une plus grande baisse chez les témoins sélectionnés en population générale ( -17,04%, IC 95%: -23,17%, -10,91%) que chez les cas (-5,99%, IC 95%: -11,50%, -0,48%). Les déterminants statistiquement significatifs du taux de réponse chez les cas étaient: le type de cancer examiné, la localisation géographique de la population de l'étude, et le mode de collecte des données. Le seul déterminant statistiquement significatif du taux de réponse chez les témoins hospitaliers était leur localisation géographique. Le seul déterminant statistiquement significatif du taux de participation chez les témoins sélectionnés en population générale était le type de répondant (sujet uniquement ou accompagné d’une tierce personne). Conclusion: Le taux de participation dans les études cas-témoins sur le cancer semble avoir diminué au cours des 30 dernières années et cette baisse serait plus marquée dans les études récentes. Afin d'évaluer le niveau réel de non-participation et ses déterminants, ainsi que l'impact de la non-participation sur la validité des études, il est nécessaire que les études publiées utilisent une approche normalisée pour calculer leurs taux de participation et qu’elles rapportent ceux-ci de façon transparente.

Subject response rates in case-control studies of cancer : time trends, study design determinants, and quality of reporting

Objectifs: Examiner les tendances temporelles, les déterminants en lien avec le design des études et la qualité des taux de réponse rapportés dans des études cas-témoins sur le cancer publiées lors des 30 dernières années. Méthodes: Une revue des études cas-témoins sur le cancer a été menée. Les critères d'inclusion étaient la publication (i) dans l’un de 15 grands périodiques ciblés et (ii) lors de quatre périodes de publication (1984-1986, 1995, 2005 et 2013) couvrant trois décennies. 370 études ont été sélectionnées et examinées. La méthodologie en lien avec le recrutement des sujets et la collecte de données, les caractéristiques de la population, les taux de participation et les raisons de la non-participation ont été extraites de ces études. Des statistiques descriptives ont été utilisées pour résumer la qualité des taux de réponse rapportés (en fonction de la quantité d’information disponible), les tendances temporelles et les déterminants des taux de réponse; des modèles de régression linéaire ont été utilisés pour analyser les tendances temporelles et les déterminants des taux de participation. Résultats: Dans l'ensemble, les qualités des taux de réponse rapportés et des raisons de non-participation étaient très faible, particulièrement chez les témoins. La participation a diminué au cours des 30 dernières années, et cette baisse est plus marquée dans les études menées après 2000. Lorsque l'on compare les taux de réponse dans les études récentes a ceux des études menées au cours de 1971 à 1980, il y a une plus grande baisse chez les témoins sélectionnés en population générale ( -17,04%, IC 95%: -23,17%, -10,91%) que chez les cas (-5,99%, IC 95%: -11,50%, -0,48%). Les déterminants statistiquement significatifs du taux de réponse chez les cas étaient: le type de cancer examiné, la localisation géographique de la population de l'étude, et le mode de collecte des données. Le seul déterminant statistiquement significatif du taux de réponse chez les témoins hospitaliers était leur localisation géographique. Le seul déterminant statistiquement significatif du taux de participation chez les témoins sélectionnés en population générale était le type de répondant (sujet uniquement ou accompagné d’une tierce personne). Conclusion: Le taux de participation dans les études cas-témoins sur le cancer semble avoir diminué au cours des 30 dernières années et cette baisse serait plus marquée dans les études récentes. Afin d'évaluer le niveau réel de non-participation et ses déterminants, ainsi que l'impact de la non-participation sur la validité des études, il est nécessaire que les études publiées utilisent une approche normalisée pour calculer leurs taux de participation et qu’elles rapportent ceux-ci de façon transparente.

Qualidade de vida de pacientes oncológicos na freqüência de um grupo de suporte multidisciplinar

As relações sociais e de apoio constituem um fator importante para melhorar a qualidade de vida dos portadores de doenças crônico-degenerativas. Neste contexto, os grupos multidisciplinares de suporte representam uma prática de atenção à saúde que evidenciam um potencial terapêutico e de aprendizagem para os pacientes, familiares e profissionais de saúde. A finalidade deste estudo foi investigar se o grupo de suporte alterou a qualidade de vida 31 de pacientes portadores de câncer. Trata-se de um estudo descritivo-exploratório com abordagem quantitativa, no qual foi utilizado o questionário EORTC-QLQ-C30, específico para mensurar a qualidade de vida de pacientes oncológicos. O EORTC-QLQ-C30 foi utilizado em duas fases: antes da adesão do paciente ao grupo e após quatro meses de participação do paciente nas atividades grupais. A comparação dos resultados das duas fases mostrou aumento dos escores das Funções e da Medida Global de Saúde e Qualidade de Vida, diminuição dos escores das escalas de sintomas, além de alterações não significativas no item Dificuldades Financeiras. Conclui-se que após as atividades grupais, houve melhora da qualidade de vida dos participantes deste estudo, exceto no que se refere à questão financeira.(AU)

Qualidade de vida de pacientes oncológicos na freqüência de um grupo de suporte multidisciplinar

As relações sociais e de apoio constituem um fator importante para melhorar a qualidade de vida dos portadores de doenças crônico-degenerativas. Neste contexto, os grupos multidisciplinares de suporte representam uma prática de atenção à saúde que evidenciam um potencial terapêutico e de aprendizagem para os pacientes, familiares e profissionais de saúde. A finalidade deste estudo foi investigar se o grupo de suporte alterou a qualidade de vida 31 de pacientes portadores de câncer. Trata-se de um estudo descritivo-exploratório com abordagem quantitativa, no qual foi utilizado o questionário EORTC-QLQ-C30, específico para mensurar a qualidade de vida de pacientes oncológicos. O EORTC-QLQ-C30 foi utilizado em duas fases: antes da adesão do paciente ao grupo e após quatro meses de participação do paciente nas atividades grupais. A comparação dos resultados das duas fases mostrou aumento dos escores das Funções e da Medida Global de Saúde e Qualidade de Vida, diminuição dos escores das escalas de sintomas, além de alterações não significativas no item Dificuldades Financeiras. Conclui-se que após as atividades grupais, houve melhora da qualidade de vida dos participantes deste estudo, exceto no que se refere à questão financeira.(AU)

CONVICÇÕES DE SAÚDE EM PACIENTES COM CÂNCER

O objetivo deste artigo é tecer algumas reflexões acerca das convicções de saúde em pacientes com câncer, participantes de um programa de atendimento multidisciplinar realizado numa universidade da Grande São Paulo. Foram utilizados depoimentos de 06 (seis) pacientes, na forma de entrevistas dirigidas e o conteúdo analisado segundo um modelo de convicção de saúde, o qual preconiza que o paciente terá maiores possibilidades de aderir aos tratamentos, seguindo cinco convicções básicas de saúde, a saber: suscetibilidade, severidade, benefícios, barreiras, eficácia própria. Uma ampliação deste modelo foi proposta por outro estudo que acrescenta mais duas categorias às já existentes: impacto ao diagnóstico e expectativas de futuro.(AU)

CONVICÇÕES DE SAÚDE EM PACIENTES COM CÂNCER

O objetivo deste artigo é tecer algumas reflexões acerca das convicções de saúde em pacientes com câncer, participantes de um programa de atendimento multidisciplinar realizado numa universidade da Grande São Paulo. Foram utilizados depoimentos de 06 (seis) pacientes, na forma de entrevistas dirigidas e o conteúdo analisado segundo um modelo de convicção de saúde, o qual preconiza que o paciente terá maiores possibilidades de aderir aos tratamentos, seguindo cinco convicções básicas de saúde, a saber: suscetibilidade, severidade, benefícios, barreiras, eficácia própria. Uma ampliação deste modelo foi proposta por outro estudo que acrescenta mais duas categorias às já existentes: impacto ao diagnóstico e expectativas de futuro.(AU)

Qualidade de vida de pacientes oncológicos na freqüência de um grupo de suporte multidisciplinar

As relações sociais e de apoio constituem um fator importante para melhorar a qualidade de vida dos portadores de doenças crônico-degenerativas. Neste contexto, os grupos multidisciplinares de suporte representam uma prática de atenção à saúde que evidenciam um potencial terapêutico e de aprendizagem para os pacientes, familiares e profissionais de saúde. A finalidade deste estudo foi investigar se o grupo de suporte alterou a qualidade de vida 31 de pacientes portadores de câncer. Trata-se de um estudo descritivo-exploratório com abordagem quantitativa, no qual foi utilizado o questionário EORTC-QLQ-C30, específico para mensurar a qualidade de vida de pacientes oncológicos. O EORTC-QLQ-C30 foi utilizado em duas fases: antes da adesão do paciente ao grupo e após quatro meses de participação do paciente nas atividades grupais. A comparação dos resultados das duas fases mostrou aumento dos escores das Funções e da Medida Global de Saúde e Qualidade de Vida, diminuição dos escores das escalas de sintomas, além de alterações não significativas no item Dificuldades Financeiras. Conclui-se que após as atividades grupais, houve melhora da qualidade de vida dos participantes deste estudo, exceto no que se refere à questão financeira.(AU)

CONVICÇÕES DE SAÚDE EM PACIENTES COM CÂNCER

O objetivo deste artigo é tecer algumas reflexões acerca das convicções de saúde em pacientes com câncer, participantes de um programa de atendimento multidisciplinar realizado numa universidade da Grande São Paulo. Foram utilizados depoimentos de 06 (seis) pacientes, na forma de entrevistas dirigidas e o conteúdo analisado segundo um modelo de convicção de saúde, o qual preconiza que o paciente terá maiores possibilidades de aderir aos tratamentos, seguindo cinco convicções básicas de saúde, a saber: suscetibilidade, severidade, benefícios, barreiras, eficácia própria. Uma ampliação deste modelo foi proposta por outro estudo que acrescenta mais duas categorias às já existentes: impacto ao diagnóstico e expectativas de futuro.(AU)

Clinical Accuracy of the MedGem Indirect Calorimeter for Measuring Resting Energy Expenditure in Cancer Patients

OBJECTIVE: To compare, in patients with cancer and in healthy subjects, measured resting energy expenditure (REE) from traditional indirect calorimetry to a new portable device (MedGem) and predicted REE. DESIGN: Cross-sectional clinical validation study. SETTING: Private radiation oncology centre, Brisbane, Australia. SUBJECTS: Cancer patients (n = 18) and healthy subjects (n = 17) aged 37-86 y, with body mass indices ranging from 18 to 42 kg/m(2). INTERVENTIONS: Oxygen consumption (VO(2)) and REE were measured by VMax229 (VM) and MedGem (MG) indirect calorimeters in random order after a 12-h fast and 30-min rest. REE was also calculated from the MG without adjustment for nitrogen excretion (MGN) and estimated from Harris-Benedict prediction equations. Data were analysed using the Bland and Altman approach, based on a clinically acceptable difference between methods of 5%. RESULTS: The mean bias (MGN-VM) was 10% and limits of agreement were -42 to 21% for cancer patients; mean bias -5% with limits of -45 to 35% for healthy subjects. Less than half of the cancer patients (n = 7, 46.7%) and only a third (n = 5, 33.3%) of healthy subjects had measured REE by MGN within clinically acceptable limits of VM. Predicted REE showed a mean bias (HB-VM) of -5% for cancer patients and 4% for healthy subjects, with limits of agreement of -30 to 20% and -27 to 34%, respectively. CONCLUSIONS: Limits of agreement for the MG and Harris Benedict equations compared to traditional indirect calorimetry were similar but wide, indicating poor clinical accuracy for determining the REE of individual cancer patients and healthy subjects.

Effects and feasibility of a multi-disciplinary orientation program for newly registered cancer patients : design of a randomised controlled trial

Background Diagnosis and treatment of cancer can contribute to psychological distress and anxiety amongst patients. Evidence indicates that information giving can be beneficial in reducing patient anxiety, so oncology specific information may have a major impact on this patient group. This study investigates the effects of an orientation program on levels of anxiety and self-efficacy amongst newly registered cancer patients who are about to undergo chemotherapy and/or radiation therapy in the cancer care centre of a large tertiary Australian hospital. Methods The concept of interventions for orienting new cancer patients needs revisiting due to the dynamic health care system. Historically, most orientation programs at this cancer centre were conducted by one nurse. A randomised controlled trial has been designed to test the effectiveness of an orientation program with bundled interventions; a face-to-face program which includes introduction to the hospital facilities, introduction to the multi-disciplinary team and an overview of treatment side effects and self care strategies. The aim is to orientate patients to the cancer centre and to meet the health care team. We hypothesize that patients who receive this orientation will experience lower levels of anxiety and distress, and a higher level of self-efficacy. Discussion An orientation program is a common health care service provided by cancer care centres for new cancer patients. Such programs aim to give information to patients at the beginning of their encounter at a cancer care centre. It is clear in the literature that interventions that aim to improve self-efficacy in patients may demonstrate potential improvement in health outcomes. Yet, evidence on the effects of orientation programs for cancer patients on self-efficacy remains scarce, particularly with respect to the use of multidisciplinary team members. This paper presents the design of a randomised controlled trial that will evaluate the effects and feasibility of a multidisciplinary orientation program for new cancer patients.