A hospital based cohort study of colorectal cancer cases treated at Braga Hospital, Northern Portugal

Background: Colorectal cancer (CRC) is the third most common cancer and the fourth most frequent cause of cancer death worldwide. Nonetheless, despite being a frequent cancer on which many epidemiological international studies have already been written, Portuguese epidemiological data are scarce and in particular there are very few specific data for Minho Region, which is traditionally recognized as a high incidence area. Aim: Characterize CRC patients treated at Braga Hospital. Methods: Data regarding clinical and preoperative diagnostic examinations, operative reports and histopathological and follow-up data was collected prospectively and stored in two Excel PC databases (colon and rectal cancer) and statistically analysed using the Statistical Package for the Social Sciences, version 19.0 (SPSS Inc., Chicago, Illinois, USA). All comparisons were examined for statistical significance using Pearson’s chi-square (?2) test and Fisher’s exact test (when n<5), with the threshold for significance P values <0.05. Overall survival and Survival free disease were both assessed using the Kaplan-Meier method. Results: The study comprises 672 patients with histological diagnosis of CRC treated in Braga Hospital between 2005 and 2009. It included 62.3% males and 37.7% females and most patients (60.5%) were between 61-80 years old. 65.3% of the cases arose from colon cancer and 34.7% from rectal cancer. We observed that 94.8% of the patients had no previous history of colorectal polyps. 4.1% had a previous personal history of CRC and 7.7% of a different cancer. 9.7% had a positive CRC family history. Most patients (81.3%) were symptomatic at diagnosis, while 18.8% were detected by routine colonoscopies. Colon and rectal cancer from most patients was at IIA stage and IV stage respectively. Follow-up time ranged between 1 and 5 years and, during this period, 26.7% of colon cancer patients and 25.3% of rectal cancer patients died from a colorectal cancer-related cause; also, 14.6% and 19.3% respectively had recurrence, mainly in the liver. Conclusion: This is the first study of a large cohort of CRC patients from the Minho Region in Northern Portugal. The large majority of the 672 cases were diagnosed because symptomatic and at an advanced stage, with a relatively poor prognosis. These findings emphasize the need to start a screening program and diagnose CRC at an early stage, thus increasing cure rates and improving resource management

Role of endoglin and VEGF family expression in colorectal cancer prognosis and anti-angiogenic therapies

Colorectal cancer (CRC) is one of the cancer models and most of the carcinogenic steps are presently well understood. Therefore, successful preventive measures are currently used in medical practice. However, CRC is still an important public health problem as it is the third most common cancer and the fourth most frequent cause of cancer death worldwide. Nowadays, pathologic stage is a unique and well-recognized prognostic indica¬tor, however, more accurate indicators of the biologic behavior of CRC are expected to improve the specificity of medical treatment. Angiogenesis plays an important role in the growth and progression of cancer but its role as a prognostic factor is still controversial. Probably the most important clinical implication of tumor angiogen¬esis is the development of anti-angiogenic therapy. The goal of this review is to critically evaluate the role of angiogenic markers, assessed by either endoglin-related microvessel density or expression of vascular endothelial growth factor family members in the CRC setting and discuss the role of these angiogenic markers in anti-angiogenic therapies

Fourier-Laplace transforms and ruin probabilities

In this paper we use Fourier/Laplace transforms to evaluate numerically relevant probabilities in ruin theory as an application to insurance. The transform of a function is split in two: the real and the imaginary parts. We use an inversion formula based on the real part only, to get the original function. By using an appropriate algorithm to compute integrals and making use of the properties of these transforms we are able to compute numerically important quantities either in classical or non-classical ruin theory. As far as the classical model is concerned the problems considered have been widely studied. In what concerns the non-classical model, in particular models based on more general renewal risk processes, there is still a long way to go. In either case the approach presented is an easy method giving good approximations for reasonable values of the initial surplus. To show this we compute numerically ruin probabilities in the classical model and in a renewal risk process in which claim inter-arrival times have an Erlang(2) distribution and compare to exact figures where available. We also consider the computation of the probability and severity of ruin in the classical model.info:eu-repo/semantics/publishedVersio

Expression of Monocarboxylate Transporters 1, 2, and 4 in Human Tumours and Their Association with CD147 and CD44

Monocarboxylate transporters (MCTs) are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein

Expression of Monocarboxylate Transporters 1, 2, and 4 in Human Tumours and Their Association with CD147 and CD44

Monocarboxylate transporters (MCTs) are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein

Expression of monocarboxylate transporters 1, 2, and 4 in human tumours and their association with CD147 and CD44

Expression of monocarboxylate transporters 1, 2, and 4 in human tumours and their association with CD147 and CD44.Monocarboxylate transporters (MCTs) are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein.Celine Pinheiro received a Ph.D. fellowship from the Portuguese Science and Technology Foundation (SFRH/BD/27465/2006). The authors acknowledge NCI (National Cancer Institute) Tumour Repository MTA, MD, USA for the multitumour tissue microarray (TARP)

Glucose addiction in cancer therapy : advances and drawbacks

Glucose addiction in cancer therapy: advances and drawbacks.In contrast to differentiated normal cells, which primarily use mitochondrial respiration to generate the energy needed for cellular processes, most cancer cells rely on glycolysis, even in sufficient oxygen conditions, a phenomenon known as the “Warburg effect” or aerobic glycolysis. In the last years, much attention to the metabolic reprogramming of cancer cells has been paid by many research groups and, as a result, this altered energy metabolism was recognized in 2011 as one of the “hallmarks of cancer”. Aerobic glycolysis allows a rapid growth of tumor cells, with high rates of glucose consumption and lactic acid production, leading to cellular acidosis. Metabolic reprogramming renders cancer cells dependent on specific metabolic enzymes or pathways that could be exploited in cancer therapy. The development of treatments that target tumor glucose metabolism is receiving renewed attention, with several drugs targeting metabolic pathways currently in clinical trials. However, the search for suitable targets may be limited by the high plasticity of the metabolic network that can induce compensatory routes. Moreover, deregulated glucose metabolism has been also shown as a prominent feature associated with resistance to either classical chemotherapy or oncogene-targeted therapies, strengthening the clinical potential of combining these therapies with glycolysis inhibitors. The aim of this review is to compare the advances of the different therapeutic strategies targeting the glucose “addiction” of tumor cells, highlighting the potential of these findings to be translated into effective weapons against cancer. Further, we will also present and discuss recent evidence for the involvement of glucose metabolism as a compensatory response to the use of drugs that target different signaling pathways, in which combination with glycolysis inhibitors are potentially useful

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Estratégias de saúde pública relativas à exposição a dioxinas : programas de vigilância epidemiológica ambiental : um exemplo de aplicação

A quantificação da exposição humana a dioxinas torna imprescindível o recurso à monitorização destes compostos no organismo humano, quando o objectivo é relacionar exposição e efeitos adversos na saúde dos indivíduos, e, por maioria de razão, quando os efeitos visados são os precoces, antes do aparecimento dos sinais clínicos. O leite materno é uma das matrizes humanas mais convenientes para a biomonitorização de dioxinas, na medida em que, embora referente a um único segmento demográfico em condições fisiológicas específicas e a um período muito reduzido na vida média dum indivíduo, permite obter informação sobre a exposição a estes compostos, quer especificamente para um importante sector da população, quer mesmo para a população geral, relativamente à qual é de extrema utilidade como indicador de exposição a este tipo de compostos, em programas de vigilância para avaliação de tendências geográficas e/ou temporais. Mas a sua maior vantagem é ainda a de poder fornecer informação sobre os níveis de dioxinas nas mulheres durante a gravidez e amamentação e, consequentemente, sobre a exposição pré-natal, dada a capacidade que as dioxinas têm de atravessar a barreira placentária e atingir o feto, e sobre a exposição pós-natal, uma vez que ocorre a transferência destes químicos, das mães aos filhos, através da amamentação, e que o leite pode constituir, para os lactentes, o único alimento, num período que não sendo muito longo na vida média de cada indivíduo, pode ser relevante em termos da exposição a estes compostos. Numa perspectiva de Saúde Pública, seria portanto desejável que qualquer estratégia relativa à exposição humana a dioxinas, desenvolvida com vista a melhorar a base de avaliação do risco para a saúde das crianças, ou para definir e adoptar medidas cientificamente fundamentadas de controlo e redução das fontes e minimização da exposição ambiental, passasse pela biomonitorização daqueles compostos no leite materno. No presente trabalho, revêem-se vantagens, desvantagens e condições da utilização do leite materno para quantificar a exposição, sobretudo perinatal, a dioxinas e descrevem-se exemplos de aplicação em curso, no âmbito de Programas de Vigilância Epidemiológica Ambiental relativos a unidades de incineração de resíduos sólidos, a operar na Área Metropolitana de Lisboa (Norte) e na Região Autónoma da Madeira

Ethics issues experienced in HBM within Portuguese health surveillance and research projects

Background: In keeping with the fundamental practice of transparency in the discussion and resolution of ethics conflicts raised by research, a summary of ethics issues raised during Portuguese biomonitoring in health surveillance and research is presented and, where applicable, their resolution is described. Methods: Projects underway aim to promote the surveillance of public health related to the presence of solid waste incinerators or to study associations between human exposure to environmental factors and adverse health effects. The methodological approach involves biomonitoring of heavy metals, dioxins and/or other persistent organic pollutants in tissues including blood, human milk and both scalp and pubic hair in groups such as the general population, children, pregnant women or women attempting pregnancy. As such, the projects entail the recruitment of individuals representing different demographic and health conditions, the collection of body tissues and personal data, and the processing of the data and results. Results: The issue of autonomy is raised during the recruitment of participants and during the collection of samples and data. This right is protected by the requirement for prior written, informed consent from the participant or, in the case of children, from their guardian. Recruitment has been successful, among eligible participants, in spite of incentives rarely being offered. The exception has been in obtaining guardians' consent for children's participation, particularly for blood sampling. In an attempt to mitigate the harm-benefit ratio, current research efforts include alternative less invasive biomarkers. Surveys are currently being conducted under contract as independent biomonitoring actions and as such, must be explicitly disclosed as a potential conflict of interests. Communication of results to participants is in general only practised when a health issue is present and corrective action possible. Concerning human milk a careful approach is taken, considering breast-feeding's proven benefits. Conclusion: No national legislation currently accounts for the surveillance component of biomonitoring as distinct from research. Ethics issues arising within the domain of research are resolved according to available regulations. For issues encountered during surveillance, the same principles are used as guidance, completed by the authors' best judgement and relevant ethics committees' findings.Fundação para a Ciência e a Tecnologia with participation by FEDER, under POCI2010; ref. POCI/ SAU-ESP/58298/2004 (VAEDA) and POCI/SAU-ESP/62115/2004 (FEXHEBIO