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Journal of Cancer Metastasis and Treatment 2023年第1期9卷 385-398页

作者： Josiany Carlos de Souza Roberto Silva Ribeiro Junior Tatiana Massariol Pimenta Bárbara da Silva Martins leticia batista azevedo rangel Postgraduate Program in Biotechnology/RENORBIO Health Sciences CenterFederal University of Espirito SantoVitória 29047-105Brazil Department of Pharmaceutical Sciences Health Sciences CenterFederal University of Espirito SantoVitória 29047-105Brazil Biochemistry Program Health Sciences CenterFederal University of Espirito SantoVitória 29047-105Brazil

Ovarian cancer(OC)is associated with poor outcomes and challenges scientists and *** is usually diagnosed in advanced stages when it is frequently aggressive,chemoresistant,and *** most prevalent form of OC is epithelial ovarian cancer(EOC),which displays significant heterogeneity,enhancing the difficulty in managing the *** factors have been associated with the disease’s development and progression,especially those related to the tumor microenvironment(TME).Here,we highlight components of the ovarian TME in the disease development process,including pro-inflammatory pathways activated by interleukins,cytokines and chemokines,cancer-associated fibroblasts,tumor-associated macrophages,and epithelial-mesenchymal *** compiled evidence identifying TME factors promoting the development,chemoresistance,and metastasis,including cytokines,chemokines,growth factors,and tumor-associated *** identify potential targets for treatment and improving *** targets block or alter pathways associated with OC(especially EOC)progression.

关键词： CAFs interleukins ovarian cancer TAMs tumor microenvironment

Novel Immunogenic Epitopes in the NaPi-IIb Protein: Production of Monospecific Antibodies Using Synthetic Peptides Outlined on Isoform Specific Regions of the Type IIb Sodium-Dependent Phosphate Transporter (NaPi-IIb)

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Journal of Cancer Therapy 2016年第2期7卷 129-151页

作者： Ângela Alice Amadeu Megale Jorge Mário da Costa Ferreira Júnior Letícia batista azevedo rangel Maria Del Pilar Estevez Diz Max Senna Mano Paulo Marcelo Gehm Hoff Priscila Hess Lopes Roberto Jun Arai Wilmar Dias da Silva Laboratório de Imunoquímica Instituto Butantan S&atildeo Paulo Brazil Departamento de Ciências Farmacêuticas Universidade Federal do Espírito Santo Espírito Santo Brazil Departamento de Pesquisa Clínica Instituto do C&acircncer do Estado de S&atildeo Paulo S&atildeo Paulo Brazil

NaPi-IIb is a multiple passage protein membrane which is primarily responsible for phosphate uptake in the kidney and in the small intestine. Beyond its physiological functions, their involvement with carcinogenesis was initially described in mid-2003, due to its distinct level of expression in normal and tumor cells of the ovary. Although less common than cervical cancer, epithelial ovarian cancer is considered the most lethal gynecologic malignancy, which is mainly due to diagnosis in the advanced stages as a result of the absence of symptoms during the onset of the disease and the lack of tools for early detection. Here, we produce antibodies that are anti-synthetic peptides that are derived from the regions of second extracellular loop of NaPi-IIb, which is a non-overlapping portion of MX35 epitope. These two 15 distinct amino acid residue peptides, designated as Let#1 and Let#2, are engineered in a very thorough way to detect specific sites only in this isoform, thus excluding cross-reactivity with other carriers of the same family. The lack of immunogenicity of small peptides is surpassed by the conjugation with carrier proteins. Using immunochemical methods, we demonstrate that polyclonal antibodies that are mono-specific for the Let#1 and Let#2 peptides recognize proteins that express similar amino acid sequences during blood circulation. Additionally, using flow cytometry, we identify NaPi-IIb in NIH:OVCAR-3 cells. The clear identification of two shorter peptides on the extracellular loop of NaPi-IIb, which are far from the monoclonal antibody MX35-recognizing epitopes, adds new promising tools for ovarian cancer follow-up and staging.

关键词： NaPi2b Peptides Antibodies Ovarian Cancer

Changes in cellular proliferation and plasma products are associated with liver failure

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World Journal of Hepatology 2016年第32期8卷 1370-1383页

作者： Juliana Gil Melgaco Frederico Marianetti Soriani Pedro Henrique Ferreira Sucupira Leonardo Assaf Pinheiro Yasmine rangel Vieira Jaqueline Mendes de Oliveira Lia Laura Lewis-Ximenez Cristina Carvalho Vianna Araújo Lúcio Filgueiras Pacheco-Moreira Gustavo batista Menezes Oswaldo Goncalves Cruz Claudia Lamarca Vitral Marcelo Alves Pinto Departamento de Microbiologia e Parasitologia Universidade Federal Fluminense Instituto Oswaldo Cruz/Fiocruz Laboratório de Desenvolvimento Tecnológico em Virologia Departamento de Biologia Geral Instituto de Ciencias BiologicasUniversidade Federal de Minas Gerais Instituto Oswaldo Cruz/Fiocruz Ambulatório de Hepatites Virais Hospital Federal de Bonsucesso Laboratório de Imunofarmacologia Departamento de Bioquímica e ImunologiaInstituto de Ciencias BiológicasUniversidade Federal de Minas Gerais Fundacao Oswaldo Cruz Programa de Computacao Científica

AIM To study the differences in immune response and cytokine profile between acute liver failure and selflimited acute *** Forty-six patients with self-limited acute hepatitis(AH), sixteen patients with acute liver failure(ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced selflimited AH and ALF. Thus, we worked with five groups: Hepatitis A virus(HAV)-induced self-limited acute hepatitis(HAV-AH), HAV-induced ALF(HAV-ALF), nonviral-induced self-limited acute hepatitis(non-viral AH), non-viral-induced acute liver failure(non-viral ALF), and healthy subjects(HC). Comparisons among HAV and non-viral-induced AH and ALF were *** The levels of mitochondrial DNA(mt DNA) and the cytokines investigated [interleukin(IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology(P < 0.05). High plasma mt DNA and IL-10 were the best markers associated with ALF [mt DNA: OR = 320.5(95%CI: 14.42-7123.33), P < 0.0001; and IL-10: OR = 18.8(95%CI: 1.38-257.94), P = 0.028] and death [mt DNA: OR = 12.1(95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01(95%CI: 1.26-50.97), P = 0.027]. In the cellular proliferation assay, NK^(bright), NKT and regulatory T cells(TReg) predominated in virusspecific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature. CONCLUSION mt DNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunologi

关键词： Acute liver failure Cytokines Mitochondrial DNA Cellular immune response Hepatitis A virus

Polymorphisms of the Toll-Like Receptor-2 Gene in Patients with Leprosy and Their Healthy Contacts

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Open Journal of Immunology 2020年第3期10卷 37-46页

作者： Luana Nepomuceno Gondim Costa Lima Letícia Siqueira Moura Jasna leticia Pinto Paz Maria do Perpétuo Socorro Amador Silvestre Daniele Melo Sardinha Letícia Diogo de Oliveira Moura Karla Valéria batista Lima Bacteriology and Mycology Section Instituto Evandro Chagas Ananindeua PA Brazil Postgraduate Program in Parasitic Biology in the Amazon at the Universidade do Estado do Pará Belém PA Brazil Postgraduate Program in Epidemiology and Health Surveillance (PPGEVS) Instituto Evandro Chagas (IEC) Ananindeua PA Brazil Graduate in Natural Sciences Universidade do Estado do Pará Belém PA Brazil Postgraduate Program in Nursing Universidade Federal do Pará Belem PA Brazil

Leprosy is an immunopathology caused by M. leprae;its evolution depends on immunological and genetic aspects of the host. The objective was verifying the relationship between SNPs 2029 and 2258 of the TLR-2 gene and leprosy. Blood samples from 127 individuals were analyzed: 45 patients, being 34 multibacillary (MB) and 11 paucibacillary (PB) and 82 contacts, in the municipalities of the State of Pará-Brazil. SNPs 2029 and 2258 of the TLR-2 gene were genotyped by sequencing on the ABI 3130 Genetic Analyzer (Applied Biosystems), analyzed using Fisher’s exact test. Distribution of SNP 2029 genotypes: all MB individuals presented the C/C genotype and the mutant (C/T) genotype was observed in contacts and PB. Alleles: all MB individuals presented only C allele and the mutant allele (T) was observed in contacts and PB. SNP 2258 genotypes: 79 contacts had G/G genotype and only 3 had G/A genotype, the MB group had only G/G genotype and the PB group was predominant G/G, with only 1 G/A genotype. Alleles: all MB individuals had allele G and the mutant allele (A) was observed in contacts and PB. The association between the SNPs and the susceptibility or protection to leprosy was not observed.

关键词： Polymorphism Toll-Like Receptors Leprosy

Specific Immunotherapy in Advanced Cervical-Uterine Cancer Using Humanized Monoclonal Antibody Nimotuzumab and CIMAvax-EGF<sup>®</sup>Therapeutic Vaccine

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Journal of Cancer Therapy 2021年第3期12卷 146-156页

作者： Raiza Ruiz-Lorente Sayly Alfonso Eduardo Santiesteban Yamilka Sánchez Kirenia Camacho Erasmo Mendoza Carmen Elena Viada Ramón Ortiz Ihosvannys Carreño Mayelin Troche Meylan Cepeda Ana Rosa Vals leticia Cabrera Annia Gorte Delmis batista Milagros Domenech Yanela Santiesteban Yuliannis Santiesteban Daymys Estevez Jessica García-Viamontes Conrado Ramos Mico Mayra Ramos-Suzarte González Coro Hospital La Habana Cuba Celestino Hernández Robau Hospital Villa Clara Cuba Jose Ramón Lopez Tabranes Hospital Matanzas Cuba III Congreso Hospital Pinar del Río Cuba Faustino Perez Hospital Matanzas Cuba Center of Molecular Immunology Havana Cuba

Cervical uterine cancer represents the fourth most common malignant neoplasm worldwide in the female sex in terms of incidence, principally from epithelial origen. The high expression of EGFR in this tumor leads to the search for therapeutic alternatives. An Expanded Access Clinical Program was carried out in parallel groups, randomized, multicenter and prospective study, to evaluate the survival of patients with advanced cervical carcinoma, without therapeutic alternative, who would be treated with the therapeutic vaccine CIMAvax-EGF®, the humanized mAb nimotuzumab or the combination of both products, which targeted EGF and EGFR respectively. The patients were included between 2008 and 2010 with a more than five years follow-up. The results show that the serious adverse events related to the experimental treatments were 0.9%;1.1% and 2.6% and a medi

关键词： CIMAvax-EGF® Nimotuzumab Survival Safety Advanced Cervical Cancer