Decomposition of stochastic flows with automorphism of subbundles component

We show that given a $G$-structure $P$ on a differentiable manifold $M$, if the group $G(M)$ of automorphisms of $P$ is big enough, then there exists the quotient of an stochastic flows $phi_t$ by $G(M)$, in the sense that $\phi_t = \xi_t \circ \rho_t$ where $\xi_t \in G(M)$, the remainder $\rho_t$ has derivative which is vertical but transversal to the fibre of $P$. This geometrical context generalizes previous results where $M$ is a Riemannian manifold and $\phi_t$ is decomposed with an isometric component, see Liao \cite{Liao1} and Ruffino \cite{Ruffino}, which in our context corresponds to the particular case of an SO(n)-structure on $M$.Comment: To appear in Stochastics and Dynamics, 201

Disminución de lesiones displásicas colónicas inducidas por 1,2–dimetilhidrazina en ratas suplementadas con ácido butírico

The butyric acid is considered as an anticancerigenous compound in several models of experimental carcinogenesis. It is one of the end products of the non–gaseous fermentation carried out by the microbial anaerobic flora of the mammalian large bowel and rumen. The milk and dairy products are the main source of butyric acid among the animal products. The aim of this study was to determine the antitumorigenic effect of butyric acid on the development of dysplastic lesions, considered as unequivocal histologic markers of colon cancer in its initial state, in 1,2–dymethylhidrazine–treated rats. Six–week–old Wistar male rats with average body weight of 160 g were used. Butyric acid was administered diluted in drinking water at the dose of 4 mg/ml for 26 weeks. Dysplastic lesions in the large bowel were induced by a weekly subcutaneous injection of 1,2–dymethylhidrazine during 17 and 5 times to respective sub–groups. Less incidence of dysplastic lesions was observed in butyric acid–supplemented groups, both in sub–group with 17 inoculations and in the sub–group with 5 inoculations, compared to control sub–groups (without supplementation). The dysplastic lesions also isplayed variation in the mucin content depending on the severity of the dysplasia. We conclude that the use of butyric acid as an antitumorigenic compound, would be the reason for the marked decrease on the development of precarcinomatous lesions, considered as important precursors of colon carcinomas. Key words: rat, dysplastic lesions, colon cancer, butiric acid, dymethylhidrazine.El ácido butírico es considerado como agente anticancerígeno en varios modelos de cáncer experimental. Constituye uno de los productos finales de la fermentación no gaseosa producida por la flora microbiana presente en intestino grueso y rumen de mamíferos. Entre los productos de origen animal, la leche y los productos lácteos constituyen una de las principales fuentes de ácido butírico. Nuestro objetivo fue evaluar el efecto anticancerígeno del acido butírico sobre el desarrollo de lesiones displásicas, consideradas marcadores histológicos de cáncer de colon en sus estadios iniciales, en ratas tratadas con el carcinógeno 1,2–dimetilhidrazina. Fueron utilizadas ratas Wistar, machos con un peso promedio de 160 g a las cuales se les administró ácido butírico puro diluido en el agua de bebida a la concentración de 4 mg/ml, durante 26 semanas. Las lesiones displásicas en el intestino grueso fueron inducidas mediante una inyección subcutánea semanal de 1,2–dimetilhidrazina durante 17 y 5 semanas a los respectivos grupos. En los lotes suplementados con ácido butírico se observó menor incidencia de lesiones displásicas tanto en el grupo tratado con 17 inoculaciones como en el grupo tratado con 5 inoculaciones, comparado con los grupos controles que no recibieron ácido butírico. Las lesiones displásicas también mostraron variación en el contenido de mucina dependiendo de la severidad de la displasia. Concluimos que la utilización de ácido butírico como agente anticancerígeno sería responsable de la marcada disminución del desarrollo de lesiones precarcinomatosas, consideradas como importantes precursores del carcinoma de colon. Palabras clave: rata, lesiones displásicas, cáncer de colon, ácido butírico, dimetilhidrazina

Nucleic Acids in Human Glioma Treatment: Innovative Approaches and Recent Results

Gliomas are the most common primary central nervous system tumors with a dismal prognosis. Despite recent advances in surgery, radiotherapy, and chemotherapy, current treatment regimens have a modest survival benefit. A crucial challenge is to deliver drugs effectively to invasive glioma cells residing in a sanctuary within the central nervous system. New therapies are essential, and oligonucleotide-based approaches, including antisense, microRNAs, small interfering RNAs, and nucleic acid aptamers, may provide a viable strategy. Thanks to their unique characteristics (low size, good affinity for the target, no immunogenicity, chemical structures that can be easily modified to improve their in vivo applications), these molecules may represent a valid alternative to antibodies particularly to overcome challenges presented by the blood-brain barrier. Here we will discuss recent results on the use of oligonucleotides that will hopefully provide new effective treatment for gliomas

Distribución de beta-catenina en lesiones displásicas de colon en ratas alimentadas con leche de búfala

El objetivo del presente trabajo fue determinar la distribución de beta-catenina en lesiones displásicas (LD) de colon en ratas alimentadas con leche de búfala. Se utilizaron ratas Wistar machos de 6 semanas, que recibieron diferentes dietas lácteas durante 123 y 240 días. Se suministraron dos tipos de dietas lácteas, una estándar, proveniente de búfalas alimentadas con pasturas naturales, y otra mejorada obtenida de búfalas suplementadas con aceite de pescado, con alto contenido en ácido linoleico conjugado y omega-3. Las LD fueron inducidas por el carcinógeno 1,2-dimetil-hidrazina. Para detectar beta-catenina se empleó la técnica de inmunohistoquímica. Las células epiteliales colónicas mostraron claramente expresión membranosa de beta-catenina. En células superficiales, la proteína pudo ser identificada también en el citoplasma, pero con una tinción membranosa más débil. En las células que estaban localizadas hacia la profundidad de la mucosa, se observó falta de proteína en el citoplasma, permaneciendo en la membrana citoplasmática. Los enterocitos ubicados sobre la muscular de la mucosa mostraron tinción membranosa débil en comparación con las membranas de las células superficiales. No se observó beta-catenina en núcleos de células normales. En LD de ratas alimentadas con leche de búfala, la distribución de beta-catenina cambió sustancialmente acorde a la severidad de la displasia. Estos hallazgos podrían ser de utilidad para la detección de lesiones pre-carcinomatosas en estadios temprano

The Mediterranean island states : Malta and Cyprus

The 2004 European Union enlargement also included the Mediterranean island-states of Cyprus and Malta, two former British colonies and members of the British Commonwealth. The islands share a number of similarities but they are also dissimilar in uniquely distinct ways. The membership applications of both states initially presented the EU with a number of political difficulties. With respect to Cyprus, many member states would have preferred to see the island join the Union after the ‘Cyprus Problem’ had been settled. As for Malta, the island showed a very high degree of Euroskepticism. It froze its application in 1996 but reactivated it in 1998. Apart from this skepticism the island’s neutral status, enshrined in the Constitution could present insurmountable problems.peer-reviewe

Axl-148b chimeric aptamers inhibit breast cancer and melanoma progression

microRNAs (miRNAs) are small non-coding RNAs acting as negative regulators of gene expression and involved in tumor progression. We recently showed that inhibition of the pro-metastatic miR-214 and simultaneous overexpression of its downstream player, the anti-metastatic miR-148b, strongly reduced metastasis formation. To explore the therapeutic potential of miR-148b, we generated a conjugated molecule aimed to target miR-148b expression selectively to tumor cells. Precisely, we linked miR-148b to GL21.T, an aptamer able to specifically bind to AXL, an oncogenic tyrosine kinase receptor highly expressed on cancer cells. Axl-148b conjugate was able to inhibit migration and invasion of AXL-positive, but not AXL-negative, cancer cells, demonstrating high efficacy and selectivity in vitro. In parallel, expression of ALCAM and ITGA5, two miR-148b direct targets, was reduced. More importantly, axl-148b chimeric aptamers were able to inhibit formation and growth of 3D-mammospheres, to induce necrosis and apoptosis of treated xenotransplants, as well as to block breast cancer and melanoma dissemination and metastatization in mice. Relevantly, axl aptamer acted as specific delivery tool for miR-148b, but it also actively contributed to inhibit metastasis formation, together with miR-148b. In conclusion, our data show that axl-148b conjugate is able to inhibit tumor progression in an axl-and miR-148b-dependent manner, suggesting its potential development as therapeutic molecule