miR-135b suppresses tumorigenesis in glioblastoma stem-like cells impairing proliferation, migration and self-renewal

Glioblastoma multiforme (GBM) is the most common and fatal malignant adult primary brain tumor. Currently, the overall prognosis for GBM patients remains poor despite advances in neurosurgery and adjuvant treatments. MicroRNAs (miRNAs) contribute to the pathogenesis of various types of tumor, including GBM. In this study we analyzed the expression of a panel of miRNAs, which are known to be differentially expressed by the brain and GBM tumor, in a collection of patient-derived GBM stem- like cells (GSCs). Notably, the average expression level of miR-135b, was the most downregulated compared to its normal counterpart, suggesting a potential role as anti-oncogene. Restoration of miR-135b in GSCs signi cantly decreased proliferation, migration and clonogenic abilities. More importantly, miR-135b restoration was able to signi cantly reduce brain in ltration in mouse models of GBM obtained by intracerebral injection of GSC lines. We identi ed ADAM12 and con rmed SMAD5 and GSK3\u3b2 as miR-135b targets and potential mediators of its effects. The whole transcriptome analysis ascertained that the expression of miR-135b downmodulated additional genes driving key pathways in GBM survival and in ltration capabilities. Our results identify a critical role of miR-135b in the regulation of GBM development, suggesting that miR-135b might act as a tumor-suppressor factor and thus providing a potential candidate for the treatment of GBM patients

Co-infection by human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type 1 (HTLV-1): does immune activation lead to a faster progression to AIDS?

<p>Abstract</p> <p>Background</p> <p>Recent data have shown that HTLV-1 is prevalent among HIV positive patients in Mozambique, although the impact of HTLV-1 infection on HIV disease progression remains controversial. Our aim was to determine the phenotypic profile of T lymphocytes subsets among Mozambican patients co-infected by HIV and HTLV-1.</p> <p>Methods</p> <p>We enrolled 29 patients co-infected by HTLV-1 and HIV (co-infected), 59 patients mono-infected by HIV (HIV) and 16 healthy controls (HC), respectively.</p> <p>For phenotypic analysis, cells were stained with the following fluorochrome-labeled anti-human monoclonal antibodies CD4-APC, CD8-PerCP, CD25-PE, CD62L-FITC, CD45RA-FITC. CD45RO-PE, CD38-PE; being analysed by four-colour flow cytometry.</p> <p>Results</p> <p>We initially found that CD4⁺T cell counts were significantly higher in co-infected, as compared to HIV groups. Moreover, CD4⁺T Lymphocytes from co-infected patients presented significantly higher levels of CD45RO and CD25, but lower levels of CD45RA and CD62L, strongly indicating that CD4⁺T cells are more activated under HTLV-1 plus HIV co-infection.</p> <p>Conclusion</p> <p>Our data indicate that HTLV-1/HIV co-infected patients progress with higher CD4⁺T cell counts and higher levels of activation markers. In this context, it is conceivable that in co-infected individuals, these higher levels of activation may account for a faster progression to AIDS.</p

Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT

Dificuldades na comunicação entre pessoas com deficiência auditiva e profissionais de saúde: uma questão de saúde pública Communication difficulties between individuals with hearing disability and health professionals: a public health matter

OBJETIVO: Descrever a ocorrência de relatos de pessoas com deficiência auditiva e múltipla (auditiva e visual e/ou mobilidade) quanto às dificuldades para ouvir e entender profissionais de saúde. MÉTODOS: Estudo transversal, do tipo inquérito de saúde, realizado com sujeitos selecionados a partir de outros dois estudos de base populacional. A coleta dos dados ocorreu de forma domiciliar, por meio de entrevistas realizadas por entrevistadores treinados, em São Paulo e região. Foram coletadas informações sobre a dificuldade de ouvir e entender o que os profissionais de saúde disseram no último serviço de saúde usado, além de dados demográficos (idade, gênero e raça), econômicos (renda do chefe da família), tipo de serviço de saúde procurado, uso de plano privado de saúde e necessidade de auxílio para ir ao serviço de saúde. RESULTADOS: Dos entrevistados, 35% relataram problemas para ouvir e entender os profissionais de saúde no último serviço visitado; 30,6% (IC95%: 23,4-37,8) para entender os médicos; 18,1% (IC95%: 12,0-24,1) para entender as enfermeiras; e 21,2% (IC95%: 14,8-27,6) para entender os outros funcionários. Não houve diferenças quando se considerou as variáveis demográficas, a necessidade de auxílio para tomar banho e se vestir, comer, levantar-se e/ou andar, possuir ou não plano privado de saúde e tipo de serviço de saúde visitado. CONCLUSÃO: Do total de pessoas entrevistadas, 35% relataram problemas para ouvir e entender o que foi dito por profissionais de saúde. Do total que relatou alguma dificuldade, 34,74% tinham deficiência auditiva e 35,38% deficiência múltipla.<br>PURPOSE: To describe the occurrence of reports from people with hearing and/or multiple disabilities (hearing and visual and/or mobility) regarding hearing and understanding health professionals. METHODS: Cross-sectional study through health survey, conducted with selected subjects from two population-based studies. Data collection took place at subjects' homes, through interviews conducted by trained interviewers in the area of São Paulo. Information regarding difficulties to hear and understand what health professionals said in the last health service used were collected, besides demographic information (age, gender and race), economic data (head of household income), type of health service sought, use of private health insurance, and need of help when accessing the health service. RESULTS: From the interviewees, 35% reported problems to hear and understand the health professionals in the last service visited; 30.6% (95%CI: 23.4-37.8) to understand the physicians; 18.1% (95%CI: 12.0-24.1) to understand the nurses; and 21.2% (95%CI: 14.8-27.6) to understand the other employees. There were no differences for the demographic variables, the need of help with bathing and dressing, eating, standing and/or walking, having or not private health insurance, and type of health service visited. CONCLUSION: From the total of individuals interviewed, 35% reported problems to hear and understand what was said by health professionals. Among these, 34.74% had hearing disability and 35.38% had multiple disabilities

Plerixafor for PBSC mobilisation in myeloma patients with advanced renal failure: safety and efficacy data in a series of 21 patients from Europe and the USA

We describe 20 patients with myeloma and 1 with primary amyloidosis from 15 centres, all with advanced renal failure, most of whom had PBSC mobilised using plerixafor following previous failed mobilisation by conventional means (plerixafor used up-front for 4 patients). For 15 patients, the plerixafor dose was reduced to 0.16 mg/kg/day, with a subsequent dose increase in one case to 0.24 mg/kg/day. The remaining six patients received a standard plerixafor dosage at 0.24 mg/kg/day. Scheduling of plerixafor and apheresis around dialysis was generally straightforward. Following plerixafor administration, all patients underwent apheresis. A median CD34+ cell dose of 4.6 × 106 per kg was achieved after 1 (n=7), 2 (n=10), 3 (n=3) or 4 (n=1) aphereses. Only one patient failed to achieve a sufficient cell dose for transplant: she subsequently underwent delayed re-mobilisation using G-CSF with plerixafor 0.24 mg/kg/day, resulting in a CD34+ cell dose of 2.12 × 106/kg. Sixteen patients experienced no plerixafor toxicities; five had mild-to-moderate gastrointestinal symptoms that did not prevent apheresis. Fifteen patients have progressed to autologous transplant, of whom 12 remain alive without disease progression. Two patients recovered endogenous renal function post autograft, and a third underwent successful renal transplantation. Plerixafor is highly effective in mobilising PBSC in this difficult patient group