BackgroundThe expression of a specific set of genes controls the different structures of heparan sulfate proteoglycans (HSPGs), which are involved in the growth, invasion and metastatic properties of cancerous cells. The purpose of this study is to increase knowledge of HSPG alterations in breast cancer.MethodsTwenty-three infiltrating ductal adenocarcinomas (IDCs), both metastatic and non-metastatic were studied. A transcriptomic approach to the structure of heparan sulfate (HS) chains was used, employing qPCR to analyze both the expression of the enzymes involved in their biosynthesis and editing, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate chains, we extended the study to include the genes involved in the biosynthesis of these glycosaminoglycans. Histochemical techniques were also used to analyze tissular expression of particular genes showing significant expression differences, of potential interest.ResultsNo significant change in transcription was detected in approximately 70% of analyzed genes. However, 13 demonstrated changes in both tumor types (40% showing more intense deregulation in the metastatic), while 5 genes showed changes only in non-metastatic tumors. Changes were related to 3 core proteins: overexpression of syndecan-1 and underexpression of glypican-3 and perlecan. HS synthesis was affected by lower levels of some 3-O-sulfotransferase transcripts, the expression of NDST4 and, only in non metastatic tumors, higher levels of extracellular sulfatases. Furthermore, the expression of chondroitin sulfate also was considerably affected, involving both the synthesis of the saccharidic chains and sulfations at all locations. However, the pro-metastatic enzyme heparanase did not exhibit significant changes in mRNA expression, although in metastatic tumors it appeared related to increased levels of the most stable form of mRNA. Finally, the expression of heparanase 2, which displays anti-metastatic features, experienced a strong deregulation in all patients analyzed.ConclusionsIDCs show alterations in the expression of HSPG genes; principally the expression and localization of proteoglycans and the sulfation patterns of glycosaminoglycan chains, depending on the metastatic nature of the tumor. In addition, the anti-proliferative molecule heparanase 2 experiences strong deregulation, thus highlighting it as a potentially interesting diagnostic factor.

RESULTADOS:La ruralización del ITS/VIH puede relacionarse con las prácticas de iniciación sexual femeninas pero sobre todo con el miedo del migrante a que su concubina tenga relaciones extra-conyugales en su ausencia. El embarazo y la crianza son recursos masculinos de control de las esposas.CONCLUSIONES: La migración de retorno implica formas de vulnerabilidad para las mujeres indígenas en las localidades estudiadas, cuya sexualidad tiene un remarcado carácter reproductivo. Es necesario implementar políticas de prevención para ITS/VIH dirigidas a fortalecer derechos sexuales y reproductivos de las mujeres y que tomen en cuenta aspectos de identidad sexual masculina.

Abstract. Molecular imaging is usually based on the recognition by the radiopharmaceuticals of specific sites which are present in limited number or density in the cells or biological tissues. Thus is of high importance to label the radiopharmaceuticals with high specific activity to be able to achieve a high target to non target ratio. The presence of carbon dioxide (CO 2 ) from the air containing 98,88% of 12 C and 1,12% 13 C compete with 11 CO 2 produced at the cyclotron. In order to minimize the presence of these isotopes along the process of irradiation, transferring and synthesis of radiopharmaceuticals labelled with 11 C, we applied this method: previous to the irradiation the target was 3-4 times flushed with He (5.7) as a cold cleaning, followed by a similar conditioning of the line, from the target up to the module, and finally a hot cleaning in order to desorb 12 CO 2 and 13 CO 2 , this was performed by irradiation during 1 min at 5 uA (3 times). In addition, with the aim of improving quality of gases in the target and in the modules, water traps (Agilent) were incorporated in the inlet lines of the target and modules. Target conditioning process (cold and hot flushings) as well as line cleaning, allowing the desorption of unlabelled CO 2 , together with the increasing of gas purity in the irradiation and in the synthesis, were critical parameters that enable to achieve 11 C-radiopharamaceuticals with high specific activity, mainly in the case of 11 C-PIB.

A new synthetic method to obtain pyridines in a one pot reaction by a modification of the Häntzsch method, in a dry medium using the NH4N03/bentonite system and microwave energy is described.

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