Oncology, Cancer Research, Molecular Medicine, Epidemiology
28
Scopus Publications
Scopus Publications
Lung Cancer in Women in Brazil: Incidence, Trends, and Overlooked Risk Factors Eldsamira Mascarenhas, Cinthya Sternberg, Sofia Vidaurre, Ellen Nascimento, Camila Greggianin, Lilian Faroni, Tercia Reis, Ana Caroline Gelatti, Clarissa Baldotto JCO Global Oncology, 2026 Lung cancer (LC) incidence and mortality rates are increasing in Brazil, particularly among women. Studies indicate that sex may affect incidence, survival, and treatment response. However, overlooked or unknown risk factors may also play a role in the sex disparities observed. For instance, although smoking is a major risk factor for LC, increasing rates of LC among nonsmoking women in Brazil, and elsewhere, have been observed. Also, traditional gender roles expose women to specific environmental hazards, as they are often expected to perform domestic tasks and thus are more likely to be indoors and exposed to second-hand smoke, air pollution from cooking fuels, and radon. In addition, occupational hazards such as formaldehyde, particularly in hairdressing, disproportionately affect women. This narrative review highlights the disparities associated with LC and female sex in Brazil, and calls for more research on these overlooked risk factors.
Oncology practice during COVID-19 pandemic: A fast response is the best response Cinthya Sternberg, Thamine Lessa Andrade, Ana Paula Gomes Alcântara Villa Nova, Bianca Vivas Fiscina, Ana Paula Laranjeira Fernandes, Camila Dias Alves, Adriana Batista Alves, Lise Oliveira Hizumi, Simone Sacramento Novais Dias, Pablicio Nobre, Aknar Calabrich, Anelisa K. Coutinho, Alex Pimenta da Silva Revista Da Associacao Medica Brasileira, 2020 SUMMARY The first confirmed case of coronavirus disease 2019 (COVID-19) in Brasil was reported on February 25th, 2020, and by April 3rd, 8076 were confirmed in the country. As COVID-19 disease incidence escalates in Brasil, management of cancer patients requires immediate action and oncology clinics are urged to establish a contingency plan. We have installed a COVID-19 Management Committee to elaborate and implement best practices to assist cancer outpatients as well as to provide a safe environment for clinical staff and other employees at the outpatient clinics. The challenges of cancer treatment in the midst of COVID-19 global pandemic highlight the importance of a rapid response by institutions, where organizational structure, strategic planning, agility in guidelines implementation and alternative ways to protect and support clinical staff, employees and patients may be the key to mitigate pandemic effects.
Cross-cultural validity study of a medical education leadership competencies instrument in Latin American physicians: A multinational study Max S. Mano, Rafaela Gomes, Gustavo Werutsky, Carlos H. Barrios, Gustavo Nader Marta, Cynthia Villarreal-Garza, Antonio Luiz Frasson, Cinthya Sternberg, Renan Clara, Sergio D. Simon, Fadil Çitaku, Marianne Waldrop, Claudio Violato, Don Zillioux, Yawar Hayat Khan Journal of Global Oncology, 2019 PURPOSE Physicians rarely receive formal training in leadership skills. Çitaku and colleagues have identified a set of leadership competencies (LCs) providing validity evidence in North American (NA) and European Union (EU) medical education institutions. We aim to apply this same survey to a sample of Latin American (LA) medical leaders from the oncology community and related areas, compare the results with those of the previous survey, and perform subgroup analyses within the LA cohort. METHODS The survey was sent to nearly 8,000 physicians of participating professional organizations. In addition to the 63 questions, we also collected data on the type of institution, country, specialty, sex, age, years of experience in oncology, and leadership position. RESULTS The 217 LA respondents placed the highest value on task management competencies (91.37% reported these as important or very important v 87.0% of NA/EU respondents; P < .0001), followed by self-management (87.45% of LA respondents v 87.55% of NA/EU respondents; P = not significant [NS]), social responsibility (86.83% of LA respondents v 87.48% of NA/EU respondents; P = NS), innovation (86.69% of LA respondents v 85.31% of NA/EU respondents; P = NS), and leading others (83.31% of LA respondents v 84.71% of NA/EU respondents; P = NS). Social responsibility, which was first in importance in the NA/EU survey, was only third in the LA survey. Subgroup analyses showed significant variations in the ratings of specific LCs within the LA population. CONCLUSION LCs valued by LA leaders somewhat differ from those valued by their NA and EU counterparts, implying that cultural aspects might influence the perception of desired LCs. We also detected variations in the responses within the LA population. Our data indicate that current physician leadership training programs should be tailored to suit specific needs and cultural aspects of each region. Further validity studies of this instrument with other samples and cultures are warranted.
Positive crosstalk between EGFR and the TF-PAR2 pathway mediates resistance to cisplatin and poor survival in cervical cancer Vitor Hugo de Almeida, Isabella dos Santos Guimarães, Lucas R. Almendra, Araci M.R. Rondon, Tatiana M. Tilli, Andréia C. de Melo, Cinthya Sternberg, Robson Q. Monteiro Oncotarget, 2018 // Vitor Hugo de Almeida 1, 2 , Isabella dos Santos Guimarães 2 , Lucas R. Almendra 1 , Araci M.R. Rondon 1 , Tatiana M. Tilli 3 , Andréia C. de Melo 2 , Cinthya Sternberg 2, 4 and Robson Q. Monteiro 1 1 Instituto de Bioquímica Médica Leopoldo De Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil 2 Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil 3 Centro de Desenvolvimento Tecnológico em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil 4 Present address: Sociedade Brasileira de Oncologia Clínica (SBOC), Belo Horizonte, MG, Brazil Correspondence to: Robson Q. Monteiro, email: robsonqm@bioqmed.ufrj.br Keywords: cervical cancer; epidermal growth factor receptor (EGFR); tissue factor (TF); protease-activated receptor 2 (PAR-2); cyclooxygenase 2 (COX-2) Received: March 07, 2018 Accepted: June 25, 2018 Published: July 17, 2018 ABSTRACT Cisplatin-based chemoradiation is the standard treatment for cervical cancer, but chemosensitizing strategies are needed to improve patient survival. EGFR ( Epidermal Growth Factor Receptor ) is an oncogene overexpressed in cervical cancer that is involved in chemoresistance. Recent studies showed that EGFR upregulates multiple elements of the coagulation cascade, including tissue factor (TF) and the protease-activated receptors (PAR) 1 and 2. Moreover, many G protein-coupled receptors, including PARs, have been implicated in EGFR transactivation. However, the role of coagulation proteins in the progression of cervical cancer has been poorly investigated. Herein we employed cervical cancer cell lines and The Cancer Genome Atlas (TCGA) database to evaluate the role of EGFR, TF and PAR2 in chemoresistance. The SLIGKL-NH2 peptide (PAR2-AP) and coagulation factor VIIa (FVIIa) were used as PAR2 agonists, while cetuximab was used to inhibit EGFR. The more aggressive cell line CASKI showed higher expression levels of EGFR, TF and PAR2 than that of C33A. PAR2 transactivated EGFR, which further upregulated cyclooxygenase-2 (COX2) expression. PAR2-AP decreased cisplatin-induced apoptosis through an EGFR- and COX2-dependent mechanism. Furthermore, treatment of CASKI cells with EGF upregulated TF expression, while treatment with cetuximab decreased the TF protein levels. The RNA-seq data from 309 TCGA samples showed a strong positive correlation between EGFR and TF expression ( P = 0.0003). In addition, the increased expression of EGFR, PAR2 or COX2 in cervical cancer patients was significantly correlated with poor overall survival. Taken together, our results suggest that EGFR and COX2 are effectors of the TF/FVIIa/PAR2 signaling pathway, promoting chemoresistance.
Targeting hodgkin and reed–sternberg cells with an inhibitor of heat-shock protein 90: Molecular pathways of response and potential mechanisms of resistance Priscilla Segges, Stephany Corrêa, Bárbara Du Rocher, Gabriela Vera-Lozada, Flavia Krsticevic, Debora Arce, Cinthya Sternberg, Eliana Abdelhay, Rocio Hassan International Journal of Molecular Sciences, 2018 Classical Hodgkin lymphoma (cHL) cells overexpress heat-shock protein 90 (HSP90), an important intracellular signaling hub regulating cell survival, which is emerging as a promising therapeutic target. Here, we report the antitumor effect of celastrol, an anti-inflammatory compound and a recognized HSP90 inhibitor, in Hodgkin and Reed–Sternberg cell lines. Two disparate responses were recorded. In KM-H2 cells, celastrol inhibited cell proliferation, induced G0/G1 arrest, and triggered apoptosis through the activation of caspase-3/7. Conversely, L428 cells exhibited resistance to the compound. A proteomic screening identified a total of 262 differentially expressed proteins in sensitive KM-H2 cells and revealed that celastrol’s toxicity involved the suppression of the MAPK/ERK (extracellular signal regulated kinase/mitogen activated protein kinase) pathway. The apoptotic effects were preceded by a decrease in RAS (proto-oncogene protein Ras), p-ERK1/2 (phospho-extracellular signal-regulated Kinase-1/2), and c-Fos (proto-oncogene protein c-Fos) protein levels, as validated by immunoblot analysis. The L428 resistant cells exhibited a marked induction of HSP27 mRNA and protein after celastrol treatment. Our results provide the first evidence that celastrol has antitumor effects in cHL cells through the suppression of the MAPK/ERK pathway. Resistance to celastrol has rarely been described, and our results suggest that in cHL it may be mediated by the upregulation of HSP27. The antitumor properties of celastrol against cHL and whether the disparate responses observed in vitro have clinical correlates deserve further research.
The use of biosimilar medicines in oncology - position statement of the brazilian society of clinical oncology (SBOC) G.S. Fernandes, C. Sternberg, G. Lopes, R. Chammas, M.A.C. Gifoni, R.A. Gil, D.V. Araujo Brazilian Journal of Medical and Biological Research, 2018 A biosimilar is a biologic product that is similar to a reference biopharmaceutical product, the manufacturing process of which hinders the ability to identically replicate the structure of the original product, and therefore, it cannot be described as an absolute equivalent of the original medication. The currently available technology does not allow for an accurate copy of complex molecules, but it does allow the replication of similar molecules with the same activity. As biosimilars are about to be introduced in oncology practice, these must be evaluated through evidence-based medicine. This manuscript is a position paper, where the Brazilian Society of Clinical Oncology (SBOC) aims to describe pertinent issues regarding the approval and use of biosimilars in oncology. As a working group on behalf of SBOC, we discuss aspects related to definition, labeling/nomenclature, extrapolation, interchangeability, switching, automatic substitution, clinical standards on safety and efficacy, and the potential impact on financial burden in healthcare. We take a stand in favor of the introduction of biosimilars, as they offer a viable, safe, and cost-effective alternative to the biopharmaceutical products currently used in cancer. We hope this document can provide valuable information to support therapeutic decisions that maximize the clinical benefit for the thousands of cancer patients in Brazil and can contribute to expedite the introduction of this new drug class in clinical practice. We expect the conveyed information to serve as a basis for further discussion in Latin America, this being the first position paper issued by a Latin American Oncology Society.
Radiotherapy modulates expression of EGFR, ERCC1 and p53 in cervical cancer V.H. de Almeida, A.C. de Melo, D.D. Meira, A.C. Pires, A. Nogueira-Rodrigues, H.K. Pimenta-Inada, F.G. Alves, G. Moralez, L.S. Thiago, C.G. Ferreira, C. Sternberg Brazilian Journal of Medical and Biological Research, 2018 Cervical cancer is a public health problem and the molecular mechanisms underlying radioresistance are still poorly understood. Here, we evaluated the modulation of key molecules involved in cell proliferation, cell cycle and DNA repair in cervical cancer cell lines (CASKI and C33A) and in malignant tissues biopsied from 10 patients before and after radiotherapy. The expression patterns of epidermal growth factor receptor (EGFR), excision repair cross-complementation group 1 (ERCC1) and p53 were evaluated in cancer cell lines by quantitative PCR and western blotting, and in human malignant tissues by immunohistochemistry. The mutation status of TP53 gene was evaluated by direct sequencing. Among cell lines, absent or weak modulations of EGFR, ERCC1 and p53 were observed after exposure to 1.8 Gy. Conversely, increased expressions of p53 (5/10 patients; P=0.0239), ERCC1 (5/10 patients; P=0.0294) and EGFR (4/10 patients; P=0.1773) were observed in malignant tissues after radiotherapy with the same radiation dose. TP53 mutations were found only in one patient. Here we show that a single dose of radiotherapy induced EGFR, ERCC1 and p53 expression in malignant tissues from cervical cancer patients but not in cancer cell lines, highlighting the gap between in vitro and in vivo experimental models. Studies on larger patient cohorts are needed to allow an interpretation that an upregulation of p53, EGFR and ERCC1 may be part of a radioresistance mechanism.
An alert to Latin America: Current human papillomavirus vaccination trends highlight key barriers to successful implementation Angelica Nogueira‐Rodrigues, Alexandra Bukowski, Eduardo Paulino, Jessica St. Louis, Adriana Barrichello, Cinthya Sternberg, Markus A. C. Gifoni, Silvana Luciani, Paul E. Goss Cancer, 2017 Human papillomavirus vaccine programs run the risk of repeating the problems associated with Papanicolaou testing programs in low‐income and middle‐income countries: an efficient, life‐saving tool that unfortunately is underused for cancer prevention. There is a great need for vigilance in the ongoing implementation of the human papillomavirus vaccine in Latin America.
XAF1 expression levels in a non-small cell lung cancer cohort and its potential association with carcinogenesis Luciene Schluckebier, Veronica Aran, Joyce De Moraes, Heitor Paiva, Cinthya Sternberg, Carlos Gil Ferreira Oncology Reports, 2017 The process of lung carcinogenesis is still not well understood and involves different levels of regulation of several genes. The search for molecular biomarkers, which can be applicable to clinical practice, has been the focus of various studies. XIAP-associated factor 1 (XAF1) was previously shown to be downregulated in many types of tumors, including squamous cell lung cancer. XAF1 is a pro-apoptotic protein and its restoration was found to sensitize cancer cells to apoptotic stimuli; however, the precise mechanism involved in the downregulation of XAF1 in tumors is unknown and promoter hypermethylation or heat-shock transcription factor 1 (HSF1) may be involved. Therefore, the aim of the present study was to evaluate the expression of XAF1 in tumors and adjacent non-tumor specimens from non-small cell lung cancer (NSCLC) patients, and its potential association with various factors including clinicopathological characteristics and other genes involved in NSCLC. Our results indicated that XAF1 expression was markedly altered in NSCLC tumor samples when compared to that found in normal lung tissues. Predominantly, XAF1 was downregulated in the tumors, except in never-smoker patients. In addition, XAF1 may also be important in the whole cell stress mechanism where the p53 status is crucial.
Planning cancer control in Latin America and the Caribbean Paul E Goss, Brittany L Lee, Tanja Badovinac-Crnjevic, Kathrin Strasser-Weippl, Yanin Chavarri-Guerra, Jessica St Louis, Cynthia Villarreal-Garza, Karla Unger-Saldaña, Mayra Ferreyra, Márcio Debiasi, Pedro ER Liedke, Diego Touya, Gustavo Werutsky, Michaela Higgins, Lei Fan, Claudia Vasconcelos, Eduardo Cazap, Carlos Vallejos, Alejandro Mohar, Felicia Knaul, Hector Arreola, Rekha Batura, Silvana Luciani, Richard Sullivan, Dianne Finkelstein, Sergio Simon, Carlos Barrios, Rebecca Kightlinger, Andres Gelrud, Vladimir Bychkovsky, Gilberto Lopes, Stephen Stefani, Marcelo Blaya, Fabiano Hahn Souza, Franklin Santana Santos, Alberto Kaemmerer, Evandro de Azambuja, Andres Felipe Cardona Zorilla, Raul Murillo, Jose Jeronimo, Vivien Tsu, Andre Carvalho, Carlos Ferreira Gil, Cinthya Sternberg, Alfonso Dueñas-Gonzalez, Dennis Sgroi, Mauricio Cuello, Rodrigo Fresco, Rui Manuel Reis, Guiseppe Masera, Raúl Gabús, Raul Ribeiro, Renata Knust, Gustavo Ismael, Eduardo Rosenblatt, Berta Roth, Luisa Villa, Argelia Lara Solares, Marta Ximena Leon, Isabel Torres-Vigil, Alfredo Covarrubias-Gomez, Andrés Hernández, Mariela Bertolino, Gilberto Schwartsmann, Sergio Santillana, Francisco Esteva, Luis Fein, Max Mano, Henry Gomez, Marc Hurlbert, Alessandra Durstine, Gustavo Azenha Lancet Oncology, 2013
Guidelines for the use and interpretation of assays for monitoring autophagy Autophagy, 2012
Redox Imbalance and Pulmonary Function in Bleomycin-Induced Fibrosis in C57BL/6, DBA/2, and BALB/c Mice Marco Aurélio Santos-Silva, Karla Maria Pereira Pires, Eduardo Tavares Lima Trajano, Vanessa Martins, Renata Tiscoski Nesi, Cláudia Farias Benjamin, Maurício Silva Caetano, Cinthya Sternberg, Mariana Nascimento Machado, Walter Araújo Zin, Samuel Santos Valença, Luis Cristóvão Porto Toxicologic Pathology, 2012
