Viral Carcinogenesis Beyond Malignant Transformation: EBV in the Progression of Human Cancers

Cancer progression begins when malignant cells colonize adjacent sites, and it is characterized by increasing tumor heterogeneity, invasion and dissemination of cancer cells. Clinically, progression is the most relevant stage in the natural history of cancers. A given virus is usually regarded as oncogenic because of its ability to induce malignant transformation of cells. Nonetheless, oncogenic viruses may also be important for the progression of infection-associated cancers. Recently this hypothesis has been addressed because of studies on the contribution of the Epstein–Barr virus (EBV) to the aggressiveness of nasopharyngeal carcinoma (NPC). Several EBV products modulate cancer progression phenomena, such as the epithelial–mesenchymal transition, cell motility, invasiveness, angiogenesis, and metastasis. In this regard, there are compelling data about the effects of EBV latent membrane proteins (LMPs) and EBV nuclear antigens (EBNAs), as well as nontranslated viral RNAs, such as the EBV-encoded small nonpolyadenylated RNAs (EBERs) and viral microRNAs, notably EBV miR-BARTs. The available data on the mechanisms and players involved in the contribution of EBV infection to the aggressiveness of NPC are discussed in this review. Overall, this conceptual framework may be valuable for the understanding of the contribution of some infectious agents in the progression of cancers

Epstein-Barr Virus (EBV) detection and typing by PCR: a contribution to diagnostic screening of EBV-positive Burkitt's lymphoma

BACKGROUND: Epstein-Barr virus (EBV) is associated to the etio-pathogenesis of an increasing number of tumors. Detection of EBV in pathology samples is relevant since its high prevalence in some cancers makes the virus a promising target of specific therapies. RNA in situ hybridization (RISH) is the standard diagnostic procedure, while polymerase chain reaction (PCR)-based methods are used for strain (EBV type-1 or 2) distinction. We performed a systematic comparison between RISH and PCR for EBV detection, in a group of childhood B-cell Non-Hodgkin lymphomas (NHL), aiming to validate PCR as a first, rapid method for the diagnosis of EBV-associated B-cell NHL. METHODS: EBV infection was investigated in formalin fixed paraffin-embedded tumor samples of 41 children with B-cell NHL, including 35 Burkitt's lymphoma (BL), from Rio de Janeiro, Brazil, by in situ hybridization of EBV-encoded small RNA (EBER-RISH) and PCR assays based on EBNA2 amplification. RESULTS: EBV genomes were detected in 68% of all NHL. Type 1 and 2 accounted for 80% and 20% of EBV infection, respectively. PCR and RISH were highly concordant (95%), as well as single- and nested-PCR results, allowing the use of a single PCR round for diagnostic purposes. PCR assays showed a sensitivity and specificity of 96% and 100%, respectively, with a detection level of 1 EBV genome in 5,000–10,000 EBV-negative cells, excluding the possibility of detecting low-number EBV-bearing memory cells. CONCLUSION: We describe adequate PCR conditions with similar sensitivity and reliability to RISH, to be used for EBV diagnostic screening in high grade B-NHL, in "at risk" geographic regions

ViriCan - Viral Carcinogenesis & Cancer Biology Research Group

Our research group aims to produce and disseminate knowledge on the role of selected human viruses in the development of human cancers, as well as to contribute for better understanding of the biology of malignant tumors. We conduct studies for a better understanding of the role of carcinogenic viruses, notably the Epstein-Barr virus (EBV) and the Kaposi Sarcoma virus (KSHV), in the etiopathogenesis of cancers in humans, whether in immunocompetent individuals or people living with the human immunodeficiency virus (HIV). Furthermore, we evaluate the possible effects of constitutional factors, viral products, natural products or other compounds on the biological aggressiveness of cancers, particularly by modifying tumor progression phenomena, such as neoplastic invasion and metastatic dissemination. Our studies are mostly based on human lymphomas, carcinomas, and sarcomas as experimental models. We are part of the Sao Paulo State University (UNESP), Botucatu School of Medicine, and our laboratory is located at the Institute for Biotechnology (IBTEC), UNESP, in Botucatu, SP, Brazil. Website: http://virican.ne

Recursos de Inteligência Artificial (IA) para empoderamento estudantil e enriquecimento da experiência de aprendizagem

Este projeto busca estimular e difundir o uso de recursos de inteligência artificial (IA), particularmente modelos massivos de linguagem (Large Language Model - LLM), abertamente disponíveis para usuários finais. O objetivo é melhorar a experiência de aprendizagem dos estudantes e aumentar seu protagonismo no processo educacional. Visa auxiliar a construção de ambientes de aprendizagem autônomos, personalizados e adaptativos, otimizando a busca de informações, sua compreensão e retenção de novos conhecimentos pelos educandos. Adicionalmente, busca fomentar uma relação mais dialógica entre educandos e educadores atuando em formas tradicionais de ensino, mediada pelas potencialidades da IA em resgatar, organizar e consolidar rapidamente dados úteis para análise crítica do atual estado do conhecimento em diferentes campos das ciências. Isso pode ser alcançado por meio da utilização de recursos que facilitem a comunicação e a troca de informações entre estudantes e professores, promovendo um enriquecimento geral da experiência de aprendizagem. English: "Artificial Intelligence (AI) Resources for Student Empowerment and Enrichment of the Learning Experience" This project aims to promote and disseminate the use of Artificial Intelligence (AI) resources, particularly Large Language Models (LLMs), openly available to end users. The objective is to enhance students' learning experience and increase their agency in the educational process. It seeks to assist in building autonomous, personalized, and adaptive learning environments, optimizing the search for information, its comprehension, and the retention of new knowledge by students. Additionally, it aims to foster a more dialogical relationship between students and educators, operating within traditional forms of teaching, mediated by the potential of AI to quickly retrieve, organize, and consolidate useful data for critical analysis of the current state of knowledge in different fields of science. This can be achieved through the use of resources that facilitate communication and information exchange between students and teachers, promoting an overall enrichment of the learning experience

Infecção pelo vírus de Epstein-Barr (EBV) e vírus do papiloma humano (HPV), expressão da proteína p53 e proliferação celular em carcinomas de nasofaringe e laringe

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Livre-docência em Biologia dos Cânceres

Materiais relacionados ao concurso de livre-docência em Biologia dos Cânceres realizado em 2019 para obtenção do título de Professor Associado junto à Universidade Estadual Paulista (UNESP), Faculdade de Medicina de Botucatu. Trabalho apresentado: ELGUI DE OLIVEIRA, D. Infecções virais e cânceres: da relação etiológica à modulação da progressão tumoral - O~caso do vírus de Epstein-Barr (EBV) e do herpesvírus do sarcoma de Kaposi (KSHV). Livre-docência - Botucatu, SP: Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, jul. 2019. 84p