Reduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells.

Qa-2 is believed to mediate a protective immune response against cancer; however, little is known about the role of Qa-2 in tumorigenesis. Here, we used 4T1 breast cancer cells to study the involvement of Qa-2 in tumor progression in a syngeneic host. Qa-2 expression was reduced during in vivo tumor growth and in cell lines derived from 4T1-induced tumors. Tumor-derived cells elicited an epithelial-mesenchymal transition associated with upregulation of Zeb1 and Twist1/2 and enhanced tumor initiating and invasive capacities. Furthermore, these cells showed increased stem characteristics, as demonstrated by upregulation of Hes1, Sox2 and Oct3/4, and enrichment of CD44high/CD24median/low cells. Remarkably, Qa-2 cell-surface expression was excluded from the CD44high/CD24median/low subpopulation. Tumor-derived cells showed increased Src activity, and treatment of these cells with the Src kinase inhibitor PP2 enhanced Qa-2 but reduced Sox2 and CD44high/CD24median/low expression levels, suggesting that Src signaling, while positively associated with stemness, negatively regulates Qa-2 expression in breast cancer. Finally, overexpression of the Qa-2 family member Q7 on the cell surface slowed down in vivo tumor growth and reduced the metastatic potential of 4T1 cells. These results suggest an anti-malignant role for Qa-2 in breast cancer development, which appears to be absent from cancer stem cells.

Preparation, physicochemical characterization, and cell viability evaluation of long-circulating and pH-sensitive liposomes containing ursolic acid.

Cancer is one of the leading causes of death worldwide. Although several drugs are used clinically, some tumors either do not respond or are resistant to the existing pharmacotherapy, thus justifying the search for new drugs. Ursolic acid (UA) is a triterpene found in different plant species that has been shown to possess significant antitumor activity. However, UA presents a low solubility in aqueous medium, which presents a barrier to its biological applications. In this context, the use of liposomes presents a promising strategy to deliver UA and allow for its intravenous administration. In this work, long-circulating and pH-sensitive liposomes containing UA (SpHL-UA) were developed, and their chemical and physicochemical properties were evaluated. SpHL-UA presented adequate properties, including a mean diameter of 191.1 ± 6.4 nm, a zeta potential of 1.2 ± 1.4 mV, and a UA entrapment of 0.77 ± 0.01 mg/mL. Moreover, this formulation showed a good stability after having been stored for 2 months at 4 °C. The viability studies on breast (MDA-MB-231) and prostate (LNCaP) cancer cell lines demonstrated that SpHL-UA treatment significantly inhibited cancer cell proliferation. Therefore, the results of the present work suggest the applicability of SpHL-UA as a new and promising anticancer formulation.

DNA MICROSATELLITES FOR GENETIC IDENTIFICATION IN BRAZILIAN MURRAH WATER BUFFALOES / DNA MICROSATELLITES FOR GENETIC IDENTIFICATION IN BRAZILIAN MURRAH WATER BUFFALOES

Atualmente, o tamanho do rebanho bubalino brasileiro (Bubalus bubalis) é de cerca de 3.000.000. Apesar deste fato, o controle genealógico ainda é um dos problemas em programas brasileiros de seleção e de melhoramento animal. O teste de DNA é importante para que se possa desenvolver um sistema que permita a certificação genealógica, bem como as inegáveis identificações individuais e de paternidade. O presente estudo teve como objetivo avaliar um painel de 14 marcadores microssatélites em búfalos brasileiros da raça Murrah (n=100), a fim de se estimar a variabilidade genética, probabilidade de exclusão de parentesco. Foram detectados 92 alelos em toda a amostragem, sendo que o número de alelos variou de um (locus D5S2) a 13 (locus CSSM47). Os valores do Contepudo de Informação Polimórfica variaram de 0,00 (locus D5S2) a 0.845 (locus BM1706). Os valores da Heterozigosidade variaram de 0,00 (locus D5S2) a 0.861 (locus BM1706). As probabilidades de exclusão de paternidade quando apenas um e ambos os pais foram analisados foram de 0,985424 (PE-1) e 0,999541 (PE-2), respectivamente. Foi observada probabilidade de exclusão de 0,999998 quando ambos os pais foram testados (PE-3) para o conjuntos dos 14 microssatélites. Este painel já é utilizado na Itália para búfalos, da raça Mediterrâneo, uma das quatro raças criadas no Brasil. No entanto, é altamente recomendável que novos loci sejam

Brazilian water buffalo (Bubalus bubalis) population is currently approximately 3,000,000. Despite of this fact, genealogical control is still one of the problems of the Brazilian selection and breeding programs. The DNA test is important to develop a system that allows the animal genealogy certification as well as its undeniable individual and parentage identification. The present study was performer by using a panel of 14 microsatellites markers in Brazilian Murrah buffaloes (n=100) in order to estimate the genetic variability and calculate the parentage exclusion probability. A total of 92 alleles were detected in the whole sample and the number of alleles varied from one (locus D5S2) to 13 (locus CSSM47). The Polymorphism Information Content values ranged from 0.00 (locus D5S2) to 0.845 (locus BM1706). Heterozygosity values ranged from 0.00 (D5S2) to 0.861 (BM1706). The paternity exclusion probabilities when only one and both parents were analyzed was 0.985424 (PE-1) and 0.999541 (PE-2), respectively. Observed a probability of exclusion of 0.999998% when both parents (PE-3) were tested for the set of 14 microsatellites. This panel is already used in Italy for the Mediterranean buffaloes, one of the four breeds raised in Brazil. However, it is highly recommended that new loci are analyzed in order to increase the microsatellites panel repertoire used for genealogical studi