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Role of cytokines and other factors involved in the Mycobacterium tuberculosis infection

World Journal of Immunology 2015年第1期5卷 16-50页

作者： tania beatriz romero-adrian Jorymar Leal-Montiel Gerardo Fernández Alejandra Valecillo Graduate Studies in Immunology Institute of Biological Research Faculty of Medicine University of Zulia Service of Pediatric Southern General Hospital Rheumatology and Immunology Service University Hospital

Mycobacterium tuberculosis （Mtb） is a pathogen that is widely distributed geographically and continues to be a major threat to world health. Bacterial virulence factors, nutritional state, host genetic condition and immune response play an important role in the evolution of the infection. The genetically diverse Mtb strains from different lineages have been shown to induce variable immune system response. The modern and ancient lineages strains induce different cytokines patterns. The immunity to Mtb depends on Th1-cell activity [interferon- γ （IFN- γ ）, interleukin-12 （IL-12） and tumor necrosis factor-α （TNF-α）]. IL-1β directly kills Mtb in murine and human macrophages. IL-6 is a requirement in host resistance to Mtb infection. IFN- γ , TNF-α, IL-12 and IL-17 are participants in Mycobacterium-induced granuloma formation. Other regulating proteins as IL-27 and IL-10 can prevent extensive immunopathology. CXCL 8 enhances the capacity of the neutrophil to kill Mtb . CXCL13 and CCL19 have been identified as participants in the formation of granuloma and control the Mtb infection. Treg cells are increased in patients with active tuberculosis （TB） but decrease with anti-TB treatment. The increment of these cells causes down- regulation of adaptive immune response facilitating the persistence of the bacterial infection. Predominance of Th2 phenotype cytokines increases the severity of TB. The evolution of the Mtb infection will depend of the cytokines network and of the infuence of other factors aforementioned.

关键词： Mycobacterium tuberculosis, Strains Virulence Host genetic Immune response T lymphocytes Cytokines

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CIMAvax^(█)EGF vaccine therapy for non-small cell lung cancer:A weighted log-rank tests-based evaluation

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Modern Chemotherapy 2013年第3期2卷 51-56页

作者： Carmen Viada Gonzalez Jean-Francois Dupuy Martha Fors López Patricia Lorenzo Luaces Gisela González Marinello Elia Neninger Vinagera beatriz García Verdecia tania Crombet-Ramos Clinical Trials Department Center of Molecular ImmunologyHavanaCuba National Institute of Applied Sciences of Rennes RennesFrance National Coordinator Center of Clinical Trial HavanaCuba Hermanos Ameijeiras Hospital HavanaCuba

Time-to-event has become one of the primary endpoints of many clinical trials. Comparing treatments and therapies using time-to-event (or “survival”) data requires some care, since survival differences may occur either early or late in the follow-up period, depending on various factors such as the initial potency or the duration of efficacy of the drugs. In this work, we investigate the effect of the CIMAvax?EGF vaccine therapy on the survival of patients with non-small cell lung cancer, using stratified and unstratified weighted log-rank tests. Weighted log-rank tests are designed to identify early and late survival differences between treatments. Using these tests, we conclude that the vaccine is more efficient than the standard therapy among patients less than 60 years of age.

关键词： Log-Rank Test Fleming-Harrington Test Stratified Tests

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Towards curative therapy in gastric cancer:Faraway, so close!

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World Journal of Gastroenterology 2015年第41期21卷 11609-11620页

作者： Marília Cravo Catarina Fidalgo Rita Garrido tania Rodrigues Gon?alo Luz Carolina Palmela Marta Santos Fábio Lopes Rui Maio Gastroenterology Department Surgery and Oncology ClinicsHospital Beatriz Angelo

Although recent diagnostic and therapeutic advances have substantially improved the survival of patients with gastric cancer(GC), the overall prognosis is still poor. Surgery is the only curative treatment and should be performed in experienced centers. Due to high relapse following surgery, complementary and systemic treatment aimed at eradicating micrometastasis should be performed in most cases. Cytotoxic treatments are effective in downstaging locally advanced cancer, but different sensitivities and toxicities probably exist in different GC subtypes. Current treatment protocols are based primarily on clinical data and histological features, but molecular biomarkers that would allow for the prediction of treatment responses are urgently needed. Understanding how host factors are responsible for inter-individual variability of drug response or toxicity will also contribute to the development of more effective and less toxic treatments.

关键词： Gastric cancer Multidisciplinary treatment Therapeutic strategies Curative surgery

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Stratified Cox Regression Analysis of Survival under CIMAvax^(■)EGF Vaccine

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Journal of Cancer Therapy 2013年第8期4卷 8-14页

作者： Carmen Viada Gonzalez Jean-Francois Dupuy Martha Fors López Patricia Lorenzo Luaces Camilo Rodríguez Rodríguez Gisela González Marinello Elia Neninger Vinagera beatriz García Verdecia Bárbara Wilkinson Brito Liana Martínez Pérez Mayelin Troche de la Concepción tania Crombet-Ramos Center of Molecular Immunology HavanaCuba Institut National des Sciences Appliquées de Rennes RennesFrance National Coordinator Center of Clinical Trial HavanaCuba Hermanos Ameijeiras Hospital HavanaCuba

Background: The Center of Molecular Immunology (CIM) is a center in Cuba devoted to the research, development and manufacturing of biotechnological products. CIMAvax?EGF is a vaccine for the treatment of non-small cell lung cancer patients (NSCL). Purpose: The aim of this work is to evaluate the effects of some potential prognostic factors on the overall survival of patients treated with CIMAvax?EGF vaccine, based on data collected in a phase II and a phase III clinical trials. Methods: The stratified Cox regression model is used to evaluate the effects of these prognostic factors, based on separate analysis for each trial, and on the combined data from both trials. Results: Patients with Performance status 0 or 1, with IV stage of tumor and male under 60 years obtain more benefit in terms of overall survival if they receive CIMAvax?EGF. Conclusions: Vaccinated group has a better performance if patients have a performance status 0 or 1, stage IV and age under 60 years. These prognostic factors influence overall survival in a positive way for those patients that received CIMAvax?EGF.

关键词： Stratified Cox Regression Model Risk Factor Non-Small Lung Cancer Censored Data

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