Distribución de Brenneria spp. en la Comunidad Valenciana y especies forestales a las que afecta

El género Brenneria agrupa especies bacterianas que producen chancros con lesiones necróticas y exudados en plantas leñosas. En España, en los últimos años, se han identificado varias Brenneria sp. como responsables de chancros bacterianos en quercíneas (B. quercina), nogales (B. nigrifluens y B. rubrifaciens) y chopos (Brenneria sp.). En la Comunidad Valenciana también se han detectado focos de B. quercina en encinas de algunos parajes de importancia medioambiental, pero todavía se dispone de escasa información acerca de la incidencia de esta bacteriosis en nuestra Comunidad. Sin embargo, no existen referencias de la presencia de Brenneria spp. en nogal o chopo en la Comunidad Valenciana, aunque no se puede descartar su presencia o introducción a través de material vegetal. El objetivo del presente trabajo ha sido conocer la incidencia de dichas bacteriosis en nuestra Comunidad. Para ello, se han continuado las prospecciones en masas de quercíneas de distintos orígenes geográficos de la Comunidad Valenciana iniciadas en un estudio anterior, y se han centrado en aquellas zonas o especies del género Quercus en las que la bacteria no había sido detectada previamente. Además, se han iniciado prospecciones en otras especies forestales de interés para nuestra Comunidad, como Juglans regia y Populus spp

Involvement of bcl-2 and p21waf1 proteins in response of human breast cancer cell clones to Tomudex

Mechanisms of resistance to Tomudex include increased thymidylate synthase activity, as well as reduced intracellular drug uptake and polyglutamation. However, little is known about other mechanisms of resistance, such as a possible protection against Tomudex-induced apoptosis mediated by bcl-2. We transfected the MDA-MB-435 human breast cancer cell line, which is characterized by a mutated p53 gene, with cDNA of the bcl-2 gene and generated two clones (MDA-bcl4 and MDA-bcl7) characterized by bcl-2 expression twofold and fourfold that observed in the control cell clone (MDAneo). A concomitant overexpression of p21wafl was also detected in the MDA-bcl7 clone. The MDA-bcl4 clone was three times more resistant to a 24-h Tomudex exposure than the MDAneo clone, whereas the MDA-bcl7 clone was as sensitive to Tomudex as the control cell clone. A lower sensitivity of the MDA-bcl4 clone than MDAneo and MDA-bcl7 clones to 5-fluorouracil and gemcitabine was also observed. No significant difference was noted in the susceptibility of clones to fludarabine and methothrexate. Basal levels of thymidylate synthase activity were superimposable in the three clones. Tomudex induced a marked accumulation of cells in the S phase in all the clones. However, an apoptotic hypodiploid DNA peak and the characteristic nuclear morphology of apoptosis were observed only in the MDA-bcl7 clone after exposure to Tomudex. No difference in the treatment-induced modulation of proteins involved in cell cycle progression (cyclin A, cdk2, pRB, E2F-1) and apoptosis (bcl-2, bax) was observed in the three clones. The only exception was that the expression of p21wafl in the MDA-bcl4 clone was inducible at a Tomudex concentration much higher than that required to induce the protein in the other clones. Overall, the results indicate that bcl-2 and p21wafl proteins concur in determining the cellular profile of sensitivity/resistance to Tomudex. © 1999 Cancer Research Campaig

4-oxo-N-(4-hydroxyphenyl)retinamide: Two Independent Ways to Kill Cancer Cells

BACKGROUND: The retinoid 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) is a polar metabolite of fenretinide (4-HPR) very effective in killing cancer cells of different histotypes, able to inhibit 4-HPR-resistant cell growth and to act synergistically in combination with the parent drug. Unlike 4-HPR and other retinoids, 4-oxo-4-HPR inhibits tubulin polymerization, leading to multipolar spindle formation and mitotic arrest. Here we investigated whether 4-oxo-4-HPR, like 4-HPR, triggered cell death also via reactive oxygen species (ROS) generation and whether its antimicrotubule activity was related to a ROS-dependent mechanism in ovarian (A2780), breast (T47D), cervical (HeLa) and neuroblastoma (SK-N-BE) cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: We provided evidence that 4-oxo-4-HPR, besides acting as an antimicrotubule agent, induced apoptosis through a signaling cascade starting from ROS generation and involving endoplasmic reticulum (ER) stress response, Jun N-terminal Kinase (JNK) activation, and upregulation of the proapoptotic PLAcental Bone morphogenetic protein (PLAB). Through time-course analysis and inhibition of the ROS-related signaling pathway (upstream by vitamin C and downstream by PLAB silencing), we demonstrated that the antimitotic activity of 4-oxo-4-HPR was independent from the oxidative stress induced by the retinoid. In fact, ROS generation occurred earlier than mitotic arrest (within 30 minutes and 2 hours, respectively) and abrogation of the ROS-related signaling pathway did not prevent the 4-oxo-4-HPR-induced mitotic arrest. CONCLUSIONS/SIGNIFICANCE: These data indicate that 4-oxo-4-HPR anticancer activity is due to at least two independent mechanisms and provide an explanation of the ability of 4-oxo-4-HPR to be more potent than the parent drug and to be effective also in 4-HPR-resistant cell lines. In addition, the double mechanism of action could allow 4-oxo-4-HPR to efficiently target tumour and to eventually counteract the development of drug resistance

Targeted doxorubicin delivery by chitosan-galactosylated modified polymer microbubbles to hepatocarcinoma cells

Targeted drug delivery is a main issue in cancer treatment. Taking advantage of recently developed polyvinyl alcohol (PVA)-based microbubbles, which are characterized by chemical versatility of the polymeric surface thereby allowing coating with different ligands, we set up a strategy for the targeted delivery of the anticancer agent doxorubicin to hepatocarcinoma cells. Such microbubbles are exceptionally efficient ultrasound scatterers and thus represent also an option as potential ultrasound contrast agents. Moreover, the oscillation of microbubbles induced by ultrasound could contribute to favor the release of drugs allocated on shell. Specifically, PVA-based microbubbles were reacted with a galactosylated chitosan complex and loaded with doxorubicin to enable the localization and drug delivery to HepG2 hepatocarcinoma cells overexpressing asialoglycoprotein receptors. We demonstrated selectivity and greater bioadhesive properties of the functionalized microbubbles for tumor cells than to normal fibroblasts, which were influenced by the degree of galactosylation. The presence of galactosylated chitosan did not modify the rate of doxorubicin release from microbubbles, whichwas almost complete within 48h. Cellular uptake of doxorubicin loaded on functionalized microbubbles was higher in HepG2 than in normal fibroblasts, which do not over express the asialoglycoprotein receptors. In addition, doxorubicin loaded onto functionalized microbubbles fully retained its cytotoxic activity. Cells were also irradiated with ultrasound, immediately after exposure to microbubbles. An early enhancement of doxorubicin release and cellular drug uptake associated to a concomitant increase in cytotoxicity was observed in HepG2 cells. Overall, results of the study indicate that galactosylated chitosan microbubbles represent promising devices for the targeted delivery of antitumor agents to liver cancer cells

El modelo psicobiológico de Cloninger en dependientes de opiáceos

Objetivo. Estudiar las relaciones entre las dimensiones de personalidad de Cloninger y el consumo de sustancias en una muestra de drogodependientes. Material y métodos. Estudio transversal. Los 196 sujetos del estudio se obtuvieron por muestreo consecutivo entre los pacientes dependientes de opiáceos que ingresaban en una Unidad de Desintoxicación Hospitalaria. A los sujetos se les evaluó con un Cuestionario de Consumo de Sustancias y el Temperament and Character Inventory. Tras el estudio descriptivo de las variables, se realizaron pruebas de diferencia de medias en las dimensiones de Cloninger comparando por un lado el grupo de politoxicómanos y el grupo de los que dependían de una sola sustancia, y por otro, varios grupos con diferentes patrones de consumo. También se estudió la correlación entre las dimensiones de Cloninger y el número de sustancias de las que dependían los sujetos y se creó un modelo de regresión lineal para evaluar si las dimensiones de personalidad permitían predecir el número de sustancias de las que dependían los sujetos. Resultados. Los resultados sugieren que la elección de las sustancias de abuso podría estar influida por variables temperamentales, mientras que la gravedad de la adicción, en concreto, el hecho de depender de una o más sustancias estaría más relacionado con variables caracteriales. Conclusiones. Recomendar la realización de más estudios, especialmente longitudinales, para confirmar las relaciones entre las dimensiones de la personalidad y la dependencia de sustancias, pues, atendiendo a los resultados expuestos, la personalidad y el abuso de sustancias están etiopatogénicamente interrelacionado