Cell therapy has been linked to an unexplained return of ovarian function and fertility in some cancer survivors. Studies modeling this in mice have shown that cells transplantation generates donor-derived oocytes in chemotherapy-treated recipients. This study was conducted to further clarify the impact of cell transplantation from different sources on female reproductive function after chemotherapy using a preclinical mouse model. Methods. Female mice were administered 7.5 mg/kg cisplatin followed by cell transplantation (one week later) using GFP+ female cell donors. For cell tracking, adipose derived stem cell GFP+ (ADSC), female germline stem cell GFP+/MVH+ (FGSC), or ovary cell suspension GFP+ mice were transplanted into cisplatin-treated wild-type recipients. After 7 or 14 days animals were killed and histological analysis, IHQ for GFP cells, and ELISA for estradiol were performed. Results. Histological examinations showed that ADSC, ovary cell suspension, and FGSC transplant increase the number of follicles with apparent normal structure in the cells recipient group euthanized on day 7. Cell tracking showed GFP+ samples 7 days after transplant. Conclusion. These data suggest that intraovarian injection of ADSCs and FGSC into mice with chemotherapy-induced ovarian failure diminished the damage caused by cisplatin.

Natural products are among one of the most promising fields in finding new molecular targets in cancer therapy. Laryngeal carcinoma is one of the most common cancers affecting the head and neck regions, and is associated with high morbidity rate if left untreated. The aim of this study was to examine the antiproliferative effect of Araucaria angustifolia on laryngeal carcinoma HEp-2 cells. The results showed that A. angustifolia extract (AAE) induced a significant cytotoxicity in HEp-2 cells compared to the non-tumor human epithelial (HEK-293) cells, indicating a selective activity of AAE for the cancer cells. A. angustifolia extract was able to increase oxidative damage to lipids and proteins, and the production of nitric oxide, along with the depletion of enzymatic antioxidant defenses (superoxide dismutase and catalase) in the tumor cell line. Moreover, AAE was able to induce DNA damage, nuclear fragmentation and chromatin condensation. A significant increase in the Apoptosis Inducing Factor (AIF), Bax, poly-(ADP-ribose) polymerase (PARP) and caspase-3 cleavage expression were also found. These effects could be related to the ability of AAE to increase the production of reactive oxygen species through inhibition of the mitochondrial electron transport chain complex I activity and ATP production by the tumor cells. The phytochemical analysis of A. angustifolia, performed using High Resolution Mass Spectrometry (HRMS) in MS and MS/MS mode, showed the presence of dodecanoic and hexadecanoic acids, and phenolic compounds, which may be associated with the chemotherapeutic effect observed in this study.

Betacellulin (BTC), a ligand of the epidermal growth factor receptor, has been shown to promote growth and differentiation of pancreatic b-cells and to improve glucose metabolism in experimental diabetic rodent models. Mesenchymal stem cells (MSCs) have been already proved to be multipotent. Recent work has attributed to rat and human MSCs the potential to differentiate into insulin-secreting cells. Our goal was to transfect rat MSCs with a plasmid containing BTC cDNA to guide MSC differentiation into insulin-producing cells. Prior to induction of cell MSC transfection, MSCs were characterized by flow cytometry and the ability to in vitro differentiate into mesoderm cell types was evaluated. After rat MSC characterization, these cells were electroporated with a plasmid containing BTC cDNA. Transfected cells were cultivated in Dulbecco's modified Eagle medium high glucose (H-DMEM) with 10 mM nicotinamide. Then, the capability of MSC-BTC to produce insulin in vitro and in vivo was evaluated. It was possible to demonstrate by radioimmunoassay analysis that 10 4 MSC-BTC cells produced up to 0.4 ng=mL of insulin, whereas MSCs transfected with the empty vector (negative control) produced no detectable insulin levels. Moreover, MSC-BTC were positive for insulin in immunohistochemistry assay. In parallel, the expression of pancreatic marker genes was demonstrated by molecular analysis of MSC-BTC. Further, when MSC-BTC were transplanted to streptozotocin diabetic rats, BTC-transfected cells ameliorated hyperglycemia from over 500 to about 200 mg=dL at 35 days post-cell transplantation. In this way, our results clearly demonstrate that BTC overabundance enhances glucose-induced insulin secretion in MSCs in vitro as well as in vivo.

RESUMOObjetivo: avaliar os padrões de imunofluorescência do fator antinuclear (FAN) em soros reagentes para anticorpos anti-SSA/Ro e sua associação clínica. Método: foi realizado um estudo transversal retrospectivo, no qual foram revisadas as solicitações de anticorpos antiantígenos nucleares extraíveis (anti-ENA) encaminhadas ao SPC/HCPA no período de dois anos. Das solicitações com resultado positivo para anti-ENA identificou-se qual ou quais auto-anticorpos estavam envolvidos (anti-SSA/Ro, anti-SSB/La, anti-RNP, anti-Sm, anti-Scl-70), bem como os padrões de imunofluorescência do FAN e os quadros clínicos dos pacientes anti-SSA/Ro positivo. As técnicas usadas para detecção e identificação foram FAN por imunofluorescência indireta (IFI) em células HEp-2 e anti-ENA por hemaglutinação. Resultados: das 392 solicitações analisadas 90 eram anti-ENA positivo. Houve um predomínio do sexo feminino (94%) (86/91) e a idade média foi de 42 anos. O anti-SSA/Ro foi o mais freqüente (67,8%) (61/90), sendo que todas as amostras anti-SSA/Ro positivas eram positivas para o FAN. O padrão de imunofluorescência nuclear pontilhado fino foi o predominante (68,9%) (42/61) nos pacientes com anti-SSA/Ro positivo, e o quadro clínico mais encontrado foi de lúpus eritematoso sistêmico, em 50,8% (31/61) dos pacientes. Conclusão: o teste de FAN por IFI utilizando células HEp-2 é um bom método de triagem para detecção de auto-anticorpos anti-SSA/Ro, apresentando maior associação com o padrão nuclear pontilhado fino. Diferente do que tem sido descrito na literatura, não encontramos nenhuma amostra de pacientes com anti-SSA/Ro que tenham apresentado FAN falso-negativo na IFI. Pelo menos na nossa experiência, esses dados questionam o custo-efetividade da solicitação de rotina desse exame em pacientes FAN negativo pelo teste de IFI.Palavras-chave: auto-anticorpo, fator antinuclear, anticorpos anti-SSA/Ro, anti-ENA. ABSTRACTObjective: to evaluate the pattern at immunofluorescence of the antinuclear antibodies (ANA) detected by the indirect immunofluorescence (IIF) technique in positive samples for anti-SSA/Ro autoantibody and the clinical associations. Methods: a retrospective transversal study was performed in a period of two years where the all the solicitations of testing for the presence of anti-extractable nuclear antigen (anti-ENA) antibodies delivered to the SPC/HCPA were analyzed. We selected the positive samples and identified which autoantibodies were involved (anti-SSA/RO, anti-SSB/La, anti-RNP, anti-Sm and anti-Scl70) as well as the immunofluorescence patterns by ANA testing and the clinical associations found in the patients presenting anti-SSA/Ro positive serum. IIF was used for ANA using HEp-2 cells and hemagglutination for anti-ENA antibodies detection. Results: 90 out of the 392 solicitations analyzed were anti-ENA positive, with a predominance of women (86/91 -94%) and the mean age was 42 years old. The most frequent autoantibody was anti-SSA/Ro (61/90 -67.8%) and all samples that were anti-SSA/Ro positive were also ANA positive...

eIF2β is involved in the protein synthesis process and should act in nuclear processes as well. eIF2βΔ3K reduces cell proliferation and causes cell death. Since translation control is essential for normal cell function and survival, the development of drugs or molecules that inhibit translation has become of great interest in the scenario of proliferative disorders. In conclusion, our results suggest the dominant negative eIF2βΔ3K as a therapeutic strategy for the treatment of proliferative disorders and that eIF2β polylysine stretch domains are promising targets for this.