Microenvironment in neuroblastoma: Isolation and characterization of tumor-derived mesenchymal stromal cells

Background: It has been proposed that mesenchymal stromal cells (MSCs) promote tumor progression by interacting with tumor cells and other stroma cells in the complex network of the tumor microenvironment. We characterized MSCs isolated and expanded from tumor tissues of pediatric patients diagnosed with neuroblastomas (NB-MSCs) to define interactions with the tumor microenvironment. Methods: Specimens were obtained from 7 pediatric patients diagnosed with neuroblastoma (NB). Morphology, immunophenotype, differentiation capacity, proliferative growth, expression of stemness and neural differentiation markers were evaluated. Moreover, the ability of cells to modulate the immune response, i.e. inhibition of phytohemagglutinin (PHA) activated peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cytotoxic function, was examined. Gene expression profiles, known to be related to tumor cell stemness, Wnt pathway activation, epithelial-mesenchymal transition (EMT) and tumor metastasis were also evaluated. Healthy donor bone marrow-derived MSCs (BM-MSC) were employed as controls. Results: NB-MSCs presented the typical MSC morphology and phenotype. They showed a proliferative capacity superimposable to BM-MSCs. Stemness marker expression (Sox2, Nanog, Oct3/4) was comparable to BM-MSCs. NB-MSC in vitro osteogenic and chondrogenic differentiation was similar to BM-MSCs, but NB-MSCs lacked adipogenic differentiation capacity. NB-MSCs reached senescence phases at a median passage of P7 (range, P5-P13). NB-MSCs exhibited greater immunosuppressive capacity on activated T lymphocytes at a 1:2 (MSC: PBMC) ratio compared with BM-MSCs (p = 0.018). NK cytotoxic activity was not influenced by co-culture, either with BM-MSCs or NB-MSCs. Flow-cytometry cell cycle analysis showed that NB-MSCs had an increased number of cells in the G0-G1 phase compared to BM-MSCs. Transcriptomic profiling results indicated that NB-MSCs were enriched with EMT genes compared to BM-MSCs. Conclusions: We characterized the biological features, the immunomodulatory capacity and the gene expression profile of NB-MSCs. The NB-MSC gene expression profile and their functional properties suggest a potential role in promoting tumor escape, invasiveness and metastatic traits of NB cancer cells. A better understanding of the complex mechanisms underlying the interactions between NB cells and NB-derived MSCs should shed new light on potential novel therapeutic approaches

Targeting MYCN in Pediatric and Adult Cancers

The deregulation of the MYC family of oncogenes, including c-MYC, MYCN and MYCL occurs in many types of cancers, and is frequently associated with a poor prognosis. The majority of functional studies have focused on c-MYC due to its broad expression profile in human cancers. The existence of highly conserved functional domains between MYCN and c-MYC suggests that MYCN participates in similar activities. MYC encodes a basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor (TF) whose central oncogenic role in many human cancers makes it a highly desirable therapeutic target. Historically, as a TF, MYC has been regarded as “undruggable”. Thus, recent efforts focus on investigating methods to indirectly target MYC to achieve anti-tumor effects. This review will primarily summarize the recent progress in understanding the function of MYCN. It will explore efforts at targeting MYCN, including strategies aimed at suppression of MYCN transcription, destabilization of MYCN protein, inhibition of MYCN transcriptional activity, repression of MYCN targets and utilization of MYCN overexpression dependent synthetic lethality

Caracterização fisico-química do leite cabras f1 (Saanen x Boer) durante a lactação

O valor nutritivo do leite, qualquer que seja a espécie que o produza é amplamente conhecido e a sua importância como alimento é maior em países subdesenvolvidos, em que as deficiências nutricionais são mais graves (DEVENDRA, 1990). Entretanto, a crescente elevação da produção leiteira tem acarretado o aumento na prevalência e na severidade das mastites e de outras doenças do úbere que ocasionam prejuízos ao criador e riscos para a saúde pública (PESSÔA, et al., 1999). São diversos os fatores que determinam a composição do leite, tais com: espécie que o produz, raça, alimentação, período de lactação, idade do animal, época do ano e a quantidade de leite produzido (FURTADO & WOLFSCHOON ? POMBO, 1978). O leite de cabra possui propriedades físicas, químicas e nutricionais particulares, e diversos autores relatam variações na sua composição físico-química (FURTADO & WOLFSCHOON ? POMBO, 1978; PRATA et al.,1998; CASTRO et al.,2002). Diante disso, o objetivo do presente estudo foi o de avaliar as características físico-químicas do leite de cabras F1 (Saanen x Boer) durante o período de lactação e determinar os valores de acidez titulável, densidade, crioscopia, teor de gordura e extrato seco total (EST) e desengordurado (ESD)

Cancer stem cell biomarkers predictive of radiotherapy response in rectal cancer: A systematic review

Background: Rectal cancer (RC) is one of the most commonly diagnosed and particularly challenging tumours to treat due to its location in the pelvis and close proximity to critical genitouri-nary organs. Radiotherapy (RT) is recognised as a key component of therapeutic strategy to treat RC, promoting the downsizing and downstaging of large RCs in neoadjuvant settings, although its therapeutic effect is limited due to radioresistance. Evidence from experimental and clinical studies indicates that the likelihood of achieving local tumour control by RT depends on the complete eradica-tion of cancer stem cells (CSC), a minority subset of tumour cells with stemness properties. Methods: A systematic literature review was conducted by querying two scientific databases (Pubmed and Scopus). The search was restricted to papers published from 2009 to 2021. Results: After assessing the quality and the risk of bias, a total of 11 studies were selected as they mainly focused on biomarkers predictive of RT-response in CSCs isolated from patients affected by RC. Specifically these studies showed that elevated levels of CD133, CD44, ALDH1, Lgr5 and G9a are associated with RT-resistance and poor prognosis. Conclusions: This review aimed to provide an overview of the current scenario of in vitro and in vivo studies evaluating the biomarkers predictive of RT-response in CSCs derived from RC patients

Avaliação sorológica de vacinas comerciais polivalentes contra a enterotoxemia em caprinos.

Foram avaliadas as respostas sorológicas a cinco vacinas comerciais polivalentes que continham o toxóide épsilon do Clostridium perfringens tipo D na sua formulação. Para isso, foram utilizados 84 caprinos jovens, divididos aleatoriamente em seis grupos experimentais com 14 animais em cada grupo. Os caprinos do Grupo Controle não receberam nenhuma dose de vacina e os dos Grupos 1 ao 5 receberam duas doses de vacina com intervalo de quatro semanas entre elas. A primeira dose de vacina foi aplicada aos 45 (± 3) dias de vida dos animais (início do experimento - dia zero) e a segunda aos 75 (± 3 ? dia 30). As amostras de sangue para a realização dos testes sorológicos foram colhidas antes (dia zero), e nos dias 30, 60, 90, 120 e 150 após o início do experimento. Utilizou-se a técnica de ELISA Indireto para quantificação dos anticorpos antitoxina épsilon do C. perfringens tipo D. De maneira geral ocorreu um aumento nos valores médios do título de anticorpos séricos dos caprinos no dia 60 em resposta às duas doses de vacina recebidas nos dias zero e 30, sendo que o maior número de animais considerados protegidos também foi detectado neste dia. Apenas cinco caprinos jovens do Grupo 1 e um do Grupo 3 permaneceram com títulos de anticorpos considerados protetores até o dia 150. Diante dos resultados obtidos, concluiu-se que as vacinas avaliadas apresentaram baixa capacidade de estimular uma resposta imune protetora nos caprinos avaliados

Presence of antibody anti-Corynebacterium pseudotuberculosis in sheep in Dormentes state fo Pernambuco, Brazil.

The Northeast has the largest Brazilian herd of goat sand sheep. Approximately 60% of these animais are located on small farms, on this fact, are the major health problems of which still exist in this region

Avaliação sorológica de vacinas comerciais polivalentes contra a enterotoxemia em caprinos.

Foram avaliadas as respostas sorológicas a cinco vacinas comerciais polivalentes que continham o toxóide épsilon do Clostridium perfringens tipo D na sua formulação. Para isso, foram utilizados 84 caprinos jovens, divididos aleatoriamente em seis grupos experimentais com 14 animais em cada grupo. Os caprinos do Grupo Controle não receberam nenhuma dose de vacina e os dos Grupos 1 ao 5 receberam duas doses de vacina com intervalo de quatro semanas entre elas. A primeira dose de vacina foi aplicada aos 45 (± 3) dias de vida dos animais (início do experimento - dia zero) e a segunda aos 75 (± 3 ? dia 30). As amostras de sangue para a realização dos testes sorológicos foram colhidas antes (dia zero), e nos dias 30, 60, 90, 120 e 150 após o início do experimento. Utilizou-se a técnica de ELISA Indireto para quantificação dos anticorpos antitoxina épsilon do C. perfringens tipo D. De maneira geral ocorreu um aumento nos valores médios do título de anticorpos séricos dos caprinos no dia 60 em resposta às duas doses de vacina recebidas nos dias zero e 30, sendo que o maior número de animais considerados protegidos também foi detectado neste dia. Apenas cinco caprinos jovens do Grupo 1 e um do Grupo 3 permaneceram com títulos de anticorpos considerados protetores até o dia 150. Diante dos resultados obtidos, concluiu-se que as vacinas avaliadas apresentaram baixa capacidade de estimular uma resposta imune protetora nos caprinos avaliados

Avaliation of antibody anti-Corynebacterium pseudotuberculosis in goats milking of Sisal area in state of Bahia.

To evaluate the presence of antibodies of these bacteria,we used 305 animais of both sexes, various breeds, older than sixmonts from 25 dairy herds located in different municipalities of the Territory of Sisal,State of Bahia

Targeting epigenetic alterations in cancer stem cells

Oncogenes or tumor suppressor genes are rarely mutated in several pediatric tumors and some early stage adult cancers. This suggests that an aberrant epigenetic reprogramming may crucially affect the tumorigenesis of these tumors. Compelling evidence support the hypothesis that cancer stem cells (CSCs), a cell subpopulation within the tumor bulk characterized by selfrenewal capacity, metastatic potential and chemo-resistance, may derive from normal stem cells (NSCs) upon an epigenetic deregulation. Thus, a better understanding of the specific epigenetic alterations driving the transformation from NSCs into CSCs may help to identify efficacious treatments to target this aggressive subpopulation. Moreover, deepening the knowledge about these alterations may represent the framework to design novel therapeutic approaches also in the field of regenerative medicine in which bioengineering of NSCs has been evaluated. Here, we provide a broad overview about: 1) the role of aberrant epigenetic modifications contributing to CSC initiation, formation and maintenance, 2) the epigenetic inhibitors in clinical trial able to specifically target the CSC subpopulation, and 3) epigenetic drugs and stem cells used in regenerative medicine for cancer and diseases