Instituto Nacional Of Cancer

Rio de Janeiro, Brazil

Instituto Nacional Of Cancer

Rio de Janeiro, Brazil
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Suarez-Kurtz G.,Instituto Nacional Of Cancer | Botton M.R.,Federal University of Rio Grande do Sul
Expert Opinion on Drug Metabolism and Toxicology | Year: 2015

Coumarin vitamin K antagonists are the mainstay of anticoagulant therapy in atrial fibrillation, prosthetic heart valves and thromboembolic conditions. Concerns with these drugs include large inter-individual variability in dose requirements, narrow therapeutic index and need to monitor prothrombin time repeatedly. Areas covered: Pharmacogenetic studies and dosing algorithms for warfarin and phenprocoumon. Expert opinion: Gene candidate studies in Brazilian patients verified consistently the association of warfarin and pheprocoumon stable dose requirements with CYP2C9 and VKORC1 polymorphisms, and minor or no influence of other pharmacogenes (e.g., CYP4F2 and F7). The predictive power of warfarin and phenprocoumon dosing algorithms developed for Brazilians compares favorably with those reported for other populations. A warfarin dosing algorithm derived for an admixed cohort performed equally well in self-reported White and Black patients, in marked contrast with the considerably poorer performance of other warfarin algorithms in patients of African descent compared to those of European ancestry. This discrepancy is ascribed to the extensive European/African admixture among Brazilians. Prospective studies of clinical utility of coumarin dosing algorithms, in the context of the Brazilian Public Health System, would represent an important counterpart to recently published trials in European and North American cohorts with predominant or exclusive European ancestry. © 2015 Informa UK, Ltd.

Calixto-Lima L.,Instituto Nacional Of Cancer
Nutrición hospitalaria : organo oficial de la Sociedad Española de Nutrición Parenteral y Enteral | Year: 2012

Antineoplastic chemotherapy (CT) represents the systemic treatment of malignant tumors. It can be used alone or combined with surgery and / or radiotherapy. The cytotoxic agents used in chemotherapy work on both cancerous cells and noncancerous cells of the body, generally resulting in high toxicity. The biological aggressiveness of chemotherapy particularly affects rapidly replicating cells, such as those of the digestive tract, resulting in adverse effects that impair food intake, leading to compromised nutritional status and which may lead to cachexia. The main toxic effects of chemotherapy in the gastrointestinal tract include nausea, vomiting -these are the most frequent- constipation, diarrhea, xerostomia, mucositis, dysphagia and anorexia. Given the high frequency of such effects, nutritional intervention should be an integral part of cancer treatment, to maintain and/or improve the patient's nutritional status and reduce or minimize the side effects caused by treatment. Accordingly, the goal of this study is to review dietetic conduct in the process of caring for patients undergoing cancer chemotherapy.

Kwee J.K.,Instituto Nacional Of Cancer
Anti-Cancer Agents in Medicinal Chemistry | Year: 2016

The ability to accumulate polyphenols with light absorbance allowed early land plants to resist UV irradiation and made survival on land possible. Largely consumed, polyphenols are not synthesized by human being. Present only in plants and some microorganisms, the number of described phenolic compounds (over 8000), is increasing due to the continual evolution of new genes and mutations in response to the adaptation to environmental changes. A wide range of biological studies revealed the antioxidant properties of polyphenols towards human pathologies such as cancer. The health benefits of polyphenols, however, depend on their amount ingested and on their bioavailability. Many factors have great influence on bioavailability of polyphenols such as the climate, agricultural practices, industrial processes and the host microbiota considered to act as a metabolic organ with an important role in human metabolism. The polyphenols anticancer effect relies on their chemical structure, concentration and on the type of cancer. The biological activity of polyphenols has been extensively studied in preclinical assays. Some polyphenols can overcome cancer chemotherapeutic resistance by modulating cancer cells with multiple drug resistance (MDR) overexpression phenotype. In solid tumours and hematological malignances, polyphenols, exert an important role in apoptosis induction, cell growth inhibition, cell cycle arrest, oxidative stress, and in cell migration and differentiation. The combination of flavonoids and chemotherapy seems to be an interesting approach for cancer treatment. In addition, some points related to the polyphenols bioavailability and delivery needs to be elucidated in order to improve their biological effects in vivo. © 2016 Bentham Science Publishers.

Suarez-Kurtz G.,Instituto Nacional Of Cancer
Pharmacogenomics | Year: 2012

There are nearly 600 million people living in 24 Latin American countries, speaking two major languages (Portuguese and Spanish) and sharing ancestral roots in America, Europe and Africa. Ethnic and cultural diversity, socioeconomical, scientific and technological disparities across Latin America must be taken into account in the design, interpretation and implications of pharmacogenomic studies in this region. The conference covered some of these aspects, but also took on a more global approach on the growing contribution of genomic information and biotechnological tools to the way medicines are developed, regulated and prescribed to patients. Translation of pharmacogenomics into clinical practice was the topic of a keynote lecture and two debate sessions. A preconference Introductory Course of Pharmacogenomics was offered. © 2012 Future Medicine Ltd.

Suarez-Kurtz G.,Instituto Nacional Of Cancer
Frontiers in Pharmacology | Year: 2010

Brazil is the fifth largest country in the world and its present population, in excess of 190 million, is highly heterogeneous, as a result of centuries of admixture between Amerindians, Europeans, and Sub-Saharan Africans. The estimated individual proportions of biogeographical ancestry vary widely and continuously among Brazilians: most individuals, irrespective of self-identification as White, Brown or Black - the major categories of the Brazilian Census "race/color" system - have significant degrees of European and African ancestry, while a sizeable number display also Amerindian ancestry. These features have important pharmacogenetic (PGx) implications: first, extrapolation of PGx data from relatively well-defined ethnic groups is clearly not applicable to the majority of Brazilians; second, the frequency distribution of polymorphisms in pharmacogenes (e.g., CYP3A5, CYP2C9, GSTM1, ABCB1, GSTM3, VKORC, etc) varies continuously among Brazilians and is not captured by race/color self-identification; third, the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of PGx studies in order to avoid spurious conclusions based on improper matching of study cohorts. The peculiarities of PGx in Brazilians are illustrated with data for different therapeutic groups, such as anticoagulants, HIV protease inhibitors and non-steroidal antinflammatory drugs, and the challenges and advantages created by population admixture for the study and implementation of PGx are discussed. PGx data for Amerindian groups and Brazilian-born, first-generation Japanese are presented to illustrate the rich diversity of the Brazilian population. Finally, I introduce the reader to the Brazilian Pharmacogenetic Network or Refargen1, a nation-wide consortium of research groups, with the mission to provide leadership in PGx research and education in Brazil, with a population health impact. © 2010 Suarez-Kurtz.

Souza-Dantas V.C.,Instituto Nacional Of Cancer | Salluh J.I.F.,Instituto Nacional Of Cancer | Soares M.,Instituto Nacional Of Cancer
Annals of Oncology | Year: 2011

Background: The prognostic effect of neutropenia in cancer patients admitted to intensive care units (ICUs) was addressed exclusively in cohort studies with conflicting results. Our aim was to address this question using a matched case-control study. Patients and methods: Ninety-four neutropenic patients and 94 non-neutropenic controls were matched for age, cancer type, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment score, and need for mechanical ventilation and vasopressors. Conditional logistic regression was used to identify factors associated with hospital mortality. Results: The ICU (66% versus 66%, P = 0.999) and hospital (73% versus 78%, P = 0.611) mortality rates were similar in neutropenic and non-neutropenic patients. Adjusting for the type of admission and length of hospital stay before ICU admission, the characteristics associated with increased mortality were the severity of acute disease and organ failures, compromised performance status and sepsis diagnosis. The impact of both previous chemotherapy and neutropenia on the outcomes was not significant. Conclusions: Using a matched case-control study design, our results provide additional evidence that the presence of neutropenia is no longer associated with worse outcomes in critically ill patients with cancer. Moreover, our results also corroborate that recent exposure to chemotherapy is not associated with increased risk for death. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Paraguassu-Braga F.H.,Instituto Nacional Of Cancer
Cell transplantation | Year: 2012

In adults, hematopoiesis takes places in the bone marrow, where specialized niches containing mesenchymal nonhematopoietic cells (stroma) harbor the hematopoietic stem cell (HSC). These niches are responsible and essential for the maintenance of HSCs. Attempts to expand HSCs fail to keep the general properties of stem cells, which depend on several niche components difficult to reproduce in in vitro culture systems. Here, we describe a methodology for in vivo study of hematopoietic stroma. We use stroma-loaded macroporous microcarriers implanted in the subcutaneous tissue of experimental animals and show that the ectopic stroma implant (ESI) is able to support hematopoiesis. Moreover, lethally irradiated mice can be rescued by ESI preloaded with HSCs, showing that they function as an ectopic bone marrow. ESI is also shown as a good system to study the role of different niche components. As an example, we used stromas lacking connexin 43 (Cx43) and confirm the importance of this molecule in the maintenance of the HSC niche in vivo. We believe ESI can work as an ectopic bone marrow allowing in vivo testing of different niches components and opening new avenues for the treatment of a variety of hematologic conditions particularly when stromal cell defects are the main cause of disease.

Bines J.,Instituto Nacional Of Cancer | Earl H.,University of Cambridge | Buzaid A.C.,Centro Oncologico Antonio Ermirio Of Moraes | Saad E.D.,University of Sao Paulo
Annals of Oncology | Year: 2014

Background: In early breast cancer, adjuvant chemotherapy decreases the risks of recurrence and breast cancer mortality, and neoadjuvant treatment leads to equivalent long-term outcomes. A large number of clinical trials have attempted to refine systemic therapeutic strategies in early breast cancer, but little attention has been paid to the sequence of anthracyclines and taxanes. Based on preclinical observations, there is limited rationale to administer the taxane before the anthracycline. Methods: We searched PubMed, the American Society of Clinical Oncology website, and with the goal of identifying published or ongoing studies that aimed at comparing reverse sequences of anthracyclines and taxanes. Given the nature and the small number of studies identified, we did not attempt to quantitatively pool the study results. Results: We retrieved seven studies in the adjuvant setting and eight in the neoadjuvant setting: 10 randomized trials (only 2 were phase IIII), 3 retrospective studies, and 2 ongoing phase II trials. A total of nearly 5000 patients were included in such studies. None of the clinical trials has shown disadvantages in terms of efficacy or toxicity for sequences in which the taxane was administered first. In the neoadjuvant setting, studies have collectively shown similar or increased pathological complete response rates for sequences in which the taxane was administered first. Conclusion: Given the available information, there seems to be sufficient evidence to suggest that a taxane followed by an anthracycline is a sequence option that can be incorporated into daily clinical practice. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

EC (oesophageal cancer) is one of the ten most frequent and fatal tumours worldwide and ESCC (oesophageal squamous cell carcinoma) accounts for about 80% of the cases. The first symptoms of ESCC arise late during the progression of the disease and, therefore, the diagnosis is usually done in advanced stages. This leads to an inefficient treatment and consequently to a poor prognosis. Thus, a comprehensive knowledge of ESCC biology is of major importance to identify risk factors, especially in high-incidence areas and biomarkers which could enable ESCC prevention and interventions throughout the natural history of the disease. In this review, we present the current knowledge regarding ESCC aetiology as well as the different genetic and epigenetic alterations already described in this tumour. We also discuss how these alterations could be used to anticipate ESCC diagnosis as well as how they can help improving treatment. A molecular natural history of the disease is proposed pointing out potential markers that may improve interventions at different points of ESCC development. Only when the different layers of complexity behind this tumour are elucidated, it will be possible to successfully perform prevention at different levels.

Modulation of intracellular antioxidant concentration is a double-edged sword, with both sides exploited for potential therapeutic benefits. While antioxidants may hamper the efficacy of chemotherapy by scavenging reactive oxygen species and free radicals, it is also possible that antioxidants alleviate unwanted chemotherapy-induced toxicity, thus allowing for increased chemotherapy doses. Under normoxic environment, antioxidants neutralize toxic oxidants, such as reactive oxygen species (ROS), maintaining them within narrow boundaries level. This redox balance is achieved by various scavenging systems such as enzymatic system (e.g., superoxide dismutases, catalase, and peroxiredoxins), nonenzymatic systems (e.g., glutathione, cysteine, and thioredoxin), and metal-binding proteins (e.g., ferritin, metallothionein, and ceruloplasmin) that sequester prooxidant metals inhibiting their participation in redox reactions. On the other hand, therapeutic strategies that promote oxidative stress and eventually tumor cells apoptosis have been explored based on availability of chemotherapy agents that inhibit ROS-scavenging systems. These contradictory assertions suggest that antioxidant supplementation during chemotherapy treatment can have varied outcomes depending on the tumor cellular context. Therefore, understanding the antioxidant-driven molecular pathways might be crucial to design new therapeutic strategies to fight cancer progression. © 2014 Jolie Kiemlian Kwee.

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