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- ItemAcesso aberto (Open Access)Potencial antitumoral de marsdenia cundurango Reichenbach F. em modelos de carcinoma mamário(Universidade Federal de São Paulo (UNIFESP), 2018-04-26) Spindola, Daniel Gonsales [UNIFESP]; Trindade, Claudia Bincoletto [UNIFESP]; http://lattes.cnpq.br/6169006634951828; http://lattes.cnpq.br/1337560649617147; Universidade Federal de São Paulo (UNIFESP)Marsdenia cundurango Reichenbach F. is a South American medicinal plant, from the Asclepiadoideae family, popularly used in treatment of stomach cancer, digestive problems and due to its anti-inflammatory and antioxidant actions. The objective of this work was to evaluate antiproliferative and antitumor activity of crude extract of Marsdenia cundurango Reichenbach F. (EBMC) and its chloroform, hexane and dichloromethane fractions obtained from organic solvents in two mammary carcinoma cell lines, MCF7 and 4T1. Cell viability was assessed after 24 hours exposure to EBMC and its fractions by trypan blue exclusion and MTT reduction assays. It was carried out the analysis of the constituents of the EBMC by UHPLC and its antioxidant profile is evaluated by the DPPH method. The incorporation of propidium iodide (PI), double-labeling with Annexin-V-FITC / PI, generation of reactive oxygen species (ROS) and mitochondrial membrane potential by DCF-DA and TMRE, respectively, and evaluation of caspase-3 activation in the 4T1 cell line, both by flow cytometry. Nuclear morphology analysis by Hoechst staining was performed by fluorescence microscopy, and the semi-quantication of Bax and Bcl-2 proteins by Western blotting. The cytosolic calcium increase was evaluated as well as an in vivo assay to evaluate the ability to reduce tumor progression in BALB / c mice. Our results demonstrated that EBMC, but not its fractions, was cytotoxic to MCF7 and 4T1 cells with the ability to reduce cell viability by 50% at a concentration of 100 μg/mL. The characterization of EBMC revealed the presence of active glycosides in it, the Condurangogligosídeos. Cell death assays demonstrated that EBMC increased the sub-G1 fraction and induced cell death, mostly late apoptosis, significantly. EBMC was also able to reduce tumor volume in in vivo assay. In addition, the nuclear morphology analysis revealed the presence of pycnotic nuclei, suggesting the occurrence of cell death. These events were accompanied by increased ROS production, decreased mitochondrial membrane potential, increased levels of Bax protein expression and decreased Bcl-2, and increased cytosolic calcium in both cell lines and activation of caspase-3 in the 4T1 cells. Thus, we conclude that EBMC has induced programmed cell death in MCF7 and 4T1 cells, and it is promising for future studies and clinical applications.
- ItemAcesso aberto (Open Access)Qualidade de vida dos pacientes com adenocarcinoma gástrico após tratamento cirúrgico com intenção curativa(Universidade Federal de São Paulo (UNIFESP), 2018-08-30) Pinheiro, Rodrigo Nascimento [UNIFESP]; Lopes Filho, Gaspar De Jesus [UNIFESP]; http://lattes.cnpq.br/3518607824692081; http://lattes.cnpq.br/5988211969382265; Universidade Federal de São Paulo (UNIFESP)Objective: To evaluate the quality of life (QoL) and identify the association among the FACT-GA and SF36 v2 scores of the QoL outcome with the sociodemographic, clinical and anatomopathological aspects of gastric adenocarcinoma patients underwent surgery with curative intent. Methods: It was made a cross-sectional study with medical charts analysis and application of questionnaires Medical Outcomes Study 36 - Item Short Form Health Survey (MOS-SF36) and Functional Assessment of Cancer Therapy – For Patients with Gastric Cancer (FACT-Ga), version 4. A total of 104 gastric adenocarcinoma patients were enrolled from three regions of Brazil. Inferential analyzes were used in the comparisons (Mann-Whitney or Kruskal-Wallis tests) and study of relationships among scores of QoL questionnaires and the variables gender, schooling, income, tumor site, type of surgery, histopathology (Lauren types), neoadjuvant and adjuvant therapies, age, postoperative time, staging, degree cell differentiation and lymphadenectomy (Spearman correlation coefficient). Results: The women presented worse quality of life (FACT-GASTRIC total score, p=0.049) and in the PWB (physical well-being; p=0.005), EWB (emotional well-being; p=0.007), GaCS (gastric cancer subscale; p=0.011), TOI (trial outcome index; p=0.030) and mental health (p=0.011). Patients with distal tumors had better quality of life scores (FACTGASTRIC total score; p = 0.018) and in the domains GaCS (p = 0.014), TOI (p = 0.020) compared to the proximal ones. Patients with cardia tumors, on the other hand, had better physical functioning scores compared to the proximal ones (p = 0.042). Patients submitted to partial gastrectomy show better total quality of life (FACT-GASTRIC total score, p = 0.011) and in the PWB (p = 0.033), GaCS (p = 0.006), TOI (p = 0.008) than total gastrectomy patients. Not using adjuvant therapy has worse scores on bodily pain than its use (p = 0.048). The higher the lymph node staging, the worse the total quality of life (total score FACT-GASTRIC, s= -0.200, p = 0.034) and the domains GaCS (s = -0.206, p = 0.037), TOI (s = -0.216; p = 0.028) and vitality (s= -0.215, p=0.029). The longer the time after treatment, the better the role-physical score (s=0.223; p=0.023).Conclusion: The type of treatment instituted, time of postoperative and socio-demographic and anatomical factors influence the QoL