Introduction: Polycystic ovarian syndrome (PCOS) is undoubtedly the commonest androgen disorder in woman's fertile period and certainly one of the most prevalent causes of anovulation. The syndrome has an estimated prevalence of 4% -10% among women of childbearing age. Previously, our group demonstrated the effect of gonadal white adipose tissue transplantation from wild-type lean and fertile female mice to isogenic obese anovulatory ob/ob mice. These complex metabolic interrelationships between obesity and PCOS have yet to be fully understood. The aim of this study was to evaluate the effect of gonadal white adipose tissue (WAT) transplantation from the wildtype lean and fertile female mice to isogenic obese, anovulatory mice (Lep ob/Lep ob) on the expression of glycolysis-and TCA cycle-related genes and obtain a general view of the glucose metabolism in the brain of these animals. Methods: Fifteen ob/ob mice ranging from 2 to 3 months of age were divided into 3 experimental groups: control normal weight (n = 5), obese control (n = 5) and obese 7 days leptin treated (n = 5). The whole brains of the mice were processed for RNA extraction. The samples from each group were used to perform PCR assays using an array plate containing 84 primers to study the glucose metabolism-related genes. Results: The glycolysis-and TCA cycle-related genes were significantly downregulated. The most significantly affected genes C. F. Baptista et al. 106 were as follows: for glycolysis (fold regulation with p < 0.05): Pgm1, Bpgm, Aldob, and Eno3 (119, 45, 18, and 28 times less, respectively); and for the TCA cycle (fold regulation with p < 0.05): Cs, Idh3b, and Mdh2 (84, 27, and 37 times less, respectively). Conclusion: The seven-day leptin treated mice show a decrease in the glucose metabolism. These results confirm the ability of the adipose tissue-derived hormone leptin to regulate early crucial genes that are related to glycolysis mechanisms and to the TCA cycle. This hormone seems to revert early the central physiological conditions that are associated with PCOS; however, the morphological alterations can only be observed within a 45-day treatment.

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Resumo de tese Palavras-chave Neoplasia trofoblástica gestacional Quimioterapia Abortamento Kewwords Gestational trophoblastic neoplasia Chemotherapy Abortion Resultados da gravidez subseqüente à quimioterapia para neoplasia trofoblástica gestacional Results of pregnancy following chemotherapy due to gestational trophoblastic neoplasia

Introduction: Mesenchymal stem cells (MSCs) are progenitor cells that can be isolated from all connective tissues such as bone, adipose, cartilage, blood and muscle. MSCs have recently been described to localize within breast carcinomas where the stem cells integrate into tumor-associated stromal tissues whereby the MSCs promote breast cancer cell invasion and metastasis. The MDA-MB-231 cell line is a triple negative lineage that likely contains more than one type of cell sub-population. It is highly aggressive, invasive and poorly differentiated. Many breast cell lines contain high percentages of the breast cancer stem cells (BSCs), despite the exactly amount be a controversial issue. Objectives: To investigate genes known to regulate the activation status of chromatin and of chromatin-related proteins and their possible differential expression values in the triple negative breast cancer (TNBC) cells MDA-MB-231 Aldefluor-positive (ALD+) and in the negative (ALD-) subpopulations. Experimental Procedures: MDA-MB-231 cells cultured in DMEM (10% fetal bovine serum) were separated in both ALD+ (BSCs) and in ALD- (non-BSCs) subpopulations by flow cytometry (Fluorescence Activated Cell Sorter — FACS). Total RNA was extracted of these cell sub-populations using TrizolTM reagent, quantified and qualified by NanodropTM and BioanalyzerTM, respectively. The total RNA was used to generate complementary DNA (cDNA) that was amplified and labeled with Cyanine 3-CTP (Cy3) to hybridization procedure. After that, these samples were submitted to One-Color Microarray-Based gene Expression Analysis. We used the SurePrint G3 slides kit (8x60K human genes) microarray formats (Agilent), scanning, and feature extraction. The analysis of differential expression profiles were performed by GX11.5 GeneSpring software. Results: Following cell sorting, gene expression values from the different experimental groups (ALD+, ALD- and control) were compared. This comparison showed us a group of upregulated DNA binding related genes. When we used ALD- group as the calibrator sample, the following upregulated fold change values from DNA binding related genes could be observed: CHD4, POLR1A, BRPF1, HIST2H4B, HMGN1, GON4L and KLF14 (respectively: 2.64, 2.94, 3.69, 3.97, 4.24, 4.41, 4.69 and 9.68; for p&lt;0.05). Besides that, when ALD+ sub-population was used as the calibrator against control cells, we observed that chromatin remodeling related genes like HIST2H4B and KLF14 were downregulated (3.46 and 8.94, respectively; for p&lt;0.05). Conclusions: Results here shown suggest that important genes playing a role in the epigenetic of cancer are upregulated in Aldefluor-positive MDA-MB-231 TNBC cells. Epigenetic aberrations might contribute to the high aggressiveness presented by these cells and overexpression of these genes might play a significant role in cancer development. Self-renewing cancer cells, often called cancer stem cells are of great interest to researchers; they often remain unaffected by currently available drugs. Therefore, these genes can be used as possible tumoral markers and also as specific molecular targets to control BSCs surveillance. Financial support: FAPESP Citation Format: Silvana Aparecida Alves Correa-Noronha, Maria de Nazareth Gamboa Ritto, Eduardo Henrique da Silva Freitas, Maria Del Carmen Molina Wolgien, Ismael Dale Cotrim Guerreiro da Silva, Samuel Marcos Ribeiro de Noronha. Chromatin-related genes are upregulated in stem cell Aldefluor-positive subpopulation of MDA-MB-231 triple-negative breast cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A51.