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1.
Olga Martinho Filipe Pinto Sara Granja Vera Miranda-Gon?alves Marise A. R. Moreira Luis F. J. Ribeiro Celso di Loreto Marsha R. Rosner Adhemar Longatto-Filho Rui Manuel Reis 《PloS one》2013,8(3)
Cervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear. In the present study, 259 uterine cervix tissues, including cervicitis, cervical intraepithelial lesions and carcinomas, were analyzed for RKIP expression by immunohistochemistry. We found that RKIP expression was significantly decreased during malignant progression, being highly expressed in non-neoplastic tissues (54% of the samples; 73/135), and expressed at low levels in the cervix invasive carcinomas (∼15% (19/124). Following in vitro downregulation of RKIP, we observed a viability and proliferative advantage of RKIP-inhibited cells over time, which was associated with an altered cell cycle distribution and higher colony number in a colony formation assay. An in vitro wound healing assay showed that RKIP abrogation is associated with increased migratory capability. RKIP downregulation was also associated with an increased vascularization of the tumors in vivo using a CAM assay. Furthermore, RKIP inhibition induced cervical cancer cells apoptotic resistance to cisplatin treatment. In conclusion, we described that RKIP protein is significantly depleted during the malignant progression of cervical tumors. Despite the lack of association with patient clinical outcome, we demonstrate, in vitro and in vivo, that loss of RKIP expression can be one of the factors that are behind the aggressiveness, malignant progression and chemotherapy resistance of cervical cancer. 相似文献
2.
Asaf Zviran Nofar Mor Yoach Rais Hila Gingold Shani Peles Elad Chomsky Sergey Viukov Jason D. Buenrostro Roberta Scognamiglio Leehee Weinberger Yair S. Manor Vladislav Krupalnik Mirie Zerbib Hadas Hezroni Diego Adhemar Jaitin David Larastiaso Shlomit Gilad Sima Benjamin Jacob H. Hanna 《Cell Stem Cell》2019,24(2):328-341.e9
3.
Ricardo Filipe Alves Costa Adhemar Longatto-Filho Céline Pinheiro Luiz Carlos Zeferino José Humberto Fregnani 《PloS one》2015,10(9)
Background
The Cervical Cancer Database of the Brazilian National Health Service (SISCOLO) contains information regarding all cervical cytological tests and, if properly explored, can be used as a tool for monitoring and managing the cervical cancer screening program. The aim of this study was to perform a historical analysis of the cervical cancer screening program in Brazil from 2006 to 2013.Material and Methods
The data necessary to calculate quality indicators were obtained from the SISCOLO, a Brazilian health system tool. Joinpoint analysis was used to calculate the annual percentage change.Results
We observed important trends showing decreased rates of low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and an increased rate of rejected exams from 2009 to 2013. The index of positivity was maintained at levels below those indicated by international standards; very low frequencies of unsatisfactory cases were observed over the study period, which partially contradicts the low rate of positive cases. The number of positive cytological diagnoses was below that expected, considering that developed countries with low frequencies of cervical cancer detect more lesions annually.Conclusions
The evolution of indicators from 2006 to 2013 suggests that actions must be taken to improve the effectiveness of cervical cancer control in Brazil. 相似文献4.
Giulliana T. Almeida Regina C. G. Lage Leticia Anderson Thiago M. Venancio Helder I. Nakaya Patrícia A. Miyasato Henrique K. Rofatto Adhemar Zerlotini Eliana Nakano Guilherme Oliveira Sergio Verjovski-Almeida 《PLoS neglected tropical diseases》2015,9(9)
BackgroundTreatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ), and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis.MethodologyWe used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP) or their combination against S. mansoni adult worms with a survival in vitro assay.ConclusionsFunctional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with either drug alone. 相似文献
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Ruiz JC D'Afonseca V Silva A Ali A Pinto AC Santos AR Rocha AA Lopes DO Dorella FA Pacheco LG Costa MP Turk MZ Seyffert N Moraes PM Soares SC Almeida SS Castro TL Abreu VA Trost E Baumbach J Tauch A Schneider MP McCulloch J Cerdeira LT Ramos RT Zerlotini A Dominitini A Resende DM Coser EM Oliveira LM Pedrosa AL Vieira CU Guimarães CT Bartholomeu DC Oliveira DM Santos FR Rabelo ÉM Lobo FP Franco GR Costa AF Castro IM Dias SR Ferro JA Ortega JM Paiva LV Goulart LR Almeida JF Ferro MI Carneiro NP 《PloS one》2011,6(4):e18551
Background
Corynebacterium pseudotuberculosis, a Gram-positive, facultative intracellular pathogen, is the etiologic agent of the disease known as caseous lymphadenitis (CL). CL mainly affects small ruminants, such as goats and sheep; it also causes infections in humans, though rarely. This species is distributed worldwide, but it has the most serious economic impact in Oceania, Africa and South America. Although C. pseudotuberculosis causes major health and productivity problems for livestock, little is known about the molecular basis of its pathogenicity.Methodology and Findings
We characterized two C. pseudotuberculosis genomes (Cp1002, isolated from goats; and CpC231, isolated from sheep). Analysis of the predicted genomes showed high similarity in genomic architecture, gene content and genetic order. When C. pseudotuberculosis was compared with other Corynebacterium species, it became evident that this pathogenic species has lost numerous genes, resulting in one of the smallest genomes in the genus. Other differences that could be part of the adaptation to pathogenicity include a lower GC content, of about 52%, and a reduced gene repertoire. The C. pseudotuberculosis genome also includes seven putative pathogenicity islands, which contain several classical virulence factors, including genes for fimbrial subunits, adhesion factors, iron uptake and secreted toxins. Additionally, all of the virulence factors in the islands have characteristics that indicate horizontal transfer.Conclusions
These particular genome characteristics of C. pseudotuberculosis, as well as its acquired virulence factors in pathogenicity islands, provide evidence of its lifestyle and of the pathogenicity pathways used by this pathogen in the infection process. All genomes cited in this study are available in the NCBI Genbank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers and CP001809. CP001829相似文献7.
Pinheiro C Longatto-Filho A Azevedo-Silva J Casal M Schmitt FC Baltazar F 《Journal of bioenergetics and biomembranes》2012,44(1):127-139
Monocarboxylate transporters (MCTs) belong to the SLC16 gene family, presently composed by 14 members. MCT1-MCT4 are proton symporters, which mediate the transmembrane transport
of pyruvate, lactate and ketone bodies. The role of MCTs in cell homeostasis has been characterized in detail in normal tissues,
however, their role in cancer is still far from understood. Most solid tumors are known to rely on glycolysis for energy production
and this activity leads to production of important amounts of lactate, which are exported into the extracellular milieu, contributing
to the acidic microenvironment. In this context, MCTs will play a dual role in the maintenance of the hyper-glycolytic acid-resistant
phenotype of cancer, allowing the maintenance of the high glycolytic rates by performing lactate efflux, and pH regulation
by the co-transport of protons. Thus, they constitute attractive targets for cancer therapy, which have been little explored.
Here we review the literature on the role of MCTs in solid tumors in different locations, such as colon, central nervous system,
breast, lung, gynecologic tract, prostate, stomach, however, there are many conflicting results and in most cases there are
no functional studies showing the dependence of the tumors on MCT expression and activity. Additional studies on MCT expression
in other tumor types, confirmation of the results already published as well as additional functional studies are needed to
deeply understand the role of MCTs in cancer maintenance and aggressiveness. 相似文献
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Teresa G. Martins Gabriela Trigo Alexandra G. Fraga José B. Gama Adhemar Longatto-Filho Margarida Saraiva Manuel T. Silva António G. Castro Jorge Pedrosa 《PLoS neglected tropical diseases》2012,6(11)
Background
Buruli ulcer (BU) is a necrotizing disease of the skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. It has been suggested that the immune response developed during the recommended rifampicin/streptomycin (RS) antibiotherapy is protective, contributing to bacterial clearance. On the other hand, paradoxical reactions have been described during or after antibiotherapy, characterized by pathological inflammatory responses. This exacerbated inflammation could be circumvented by immunosuppressive drugs. Therefore, it is important to clarify if the immune system contributes to bacterial clearance during RS antibiotherapy and if immunosuppression hampers the efficacy of the antibiotic regimen.Methodology/Principal Findings
We used the M. ulcerans infection footpad mouse model. Corticosteroid-induced immunosuppression was achieved before experimental infection and maintained during combined RS antibiotherapy by the administration of dexamethasone (DEX). Time-lapsed analyses of macroscopic lesions, bacterial burdens, histology and immunohistochemistry were performed in M. ulcerans-infected footpads. We show here that corticosteroid-immunosuppressed mice are more susceptible to M. ulcerans, with higher bacterial burdens and earlier ulceration. Despite this, macroscopic lesions remised during combined antibiotic/DEX treatment and no viable bacteria were detected in the footpads after RS administration. This was observed despite a delayed kinetics in bacterial clearance, associated with a local reduction of T cell and neutrophil numbers, when compared with immunocompetent RS-treated mice. In addition, no relapse was observed following an additional 3 month period of DEX administration.Conclusions/Significance
These findings reveal a major role of the RS bactericidal activity for the resolution of M. ulcerans experimental infections even during immunosuppression, and support clinical investigation on the potential use of corticosteroids or other immunosuppressive/anti-inflammatory drugs for the management of BU patients undergoing paradoxical reactions. 相似文献10.
Camargo RS Shirata NK di Loreto C Garcia EA Castelo A Longatto Filho A 《Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology》2006,28(4):188-192
OBJECTIVE: To evaluate the discriminating potential of AgNOR area measurement and count in thyroid tumors using static cytometry equipment. STUDY DESIGN: Slides were analyzed by a computerized system for image analysis, CAS 200 (Becton & Dickinson, U.S.A.), using the Cell Measurement computer program (CAS 200, Becton & Dickinson). The argyrophilic reaction (NORs) was evaluated with a 400-fold amplification directly from the computer monitor. RESULTS: Thirty-three cases were analyzed for AgNOR staining. The cases studied included 3 goiters, 10 follicular adenomas, 6 Hürthle adenomas, 4 follicular carcinomas, 7 papillary carcinomas, and 3 Hürthle carcinomas. A total of 6,600 nuclei were evaluated. For statistical purposes, lesions were classified as benign and malignant, and both the number and the area of counted NORs showed very similar values. The NORs median among 19 benign tumors was 1.484 (SD +/- 0.265) and of 14 malignant tumors was 1.436 (SD +/- 0.414); the NORs areas were 2.6584 (SD +/- 1.0653) and 2.3643 (SD +/- 0.6320), respectively. CONCLUSION: Our results showed that AgNOR evaluation was not a significant parameter to discriminate between malignant and benign thyroid lesions. 相似文献