Gene Expression Analyses in Non Muscle Invasive Bladder Cancer Reveals a Role for Alternative Splicing and Tp53 Status

Non-muscle invasive bladder cancer (NMIBC) represents a crucial problem for the national health care systems due to its high rates of recurrence and the consequent need of frequent follow-ups. Here, gene expression analyses in patients diagnosed as NMIBC were performed to determine those molecular pathways involved in tumor initiation, finding that both MYC and E2F are up regulated and helps to tumor initiation and progression. Our results also support an important involvement of alternative splicing events, modifying key pathways to favour bladder tumor evolution. Finally, since MDM2 showed differential exon usage, mutations in TP53 and its protein expression have been also studied in the same patients. Our data support that recurrence is epigenetically mediated and favoured by an increase protein expression of TP53, which appears more frequently mutated in advanced stages and grades, being associated to a worse prognosis. Therefore, TP53 mutational status could be used as a potential biomarker in the first stages of NMIBC to predict recurrence and prognosis

Integral parametrization of the kinetics of crosslink production in plasmid DNA as a function of 8-methoxy-psoralen concentration

Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai

Implicacion de los genes uvra y reca de E. coli k 12 en la reparacion de monoaductos y entrecruzamientos inducidos en DNA plasmidico por 8-metoxipsoraleno mas luz ultravioleta A

Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai

Phototrexate : a novel drug candidate for cancer and psoriasis

Antifolates are structural analogs of folates, essential one-carbon donors in the synthesis of DNA in mammalian cells, and they work as inhibitors of key enzymes in folate metabolism, such as dihydrofolate reductase and thymidylate synthetase. Methotrexate (MTX) was one of the first agents of this class and is still extensively used in the treatment of a variety of tumors, including acute lymphocytic leukemia, breast cancer, osteosarcoma, primary central nervous system lymphoma, and head and neck cancer. Above all, it is also commonly used in certain autoimmune diseases, such as rheumatoid arthritis or psoriasis. However, the clinical efficacy of MTX is often limited and compromised by toxic dose-related side effects, which leads to morbidity, interruption of the treatment, and occasional mortality. A promising approach to tackle this problem is to activate the drug exclusively at its desired place of action. In fact, in those diseases that would benefit from a highly localized treatment, a precise spatiotemporal control over the activity of a chemotherapeutic agent would allow reducing the concentration of active compound outside the target tissue, improving the tolerability and hence the efficacy of the treatment. Light is a powerful tool in this respect: it offers unparalleled opportunities as a non-invasive regulatory signal for pharmacological applications because it can be delivered with high precision regarding space, time, intensity and wavelength. We have recently developed Phototrexate, the first photoswitchable antifolate, by incorporation of a photochromic unit into the structure of MTX. Phototrexate was designed to be constitutively inactive in its thermodynamically stable configuration (E isomer), while it can be activated with light (Z isomer) to locally provide the pharmacological effects of the parent drug, as confirmed in our earlier experiments in vitro and in zebrafish larvae. Studies are currently underway to assess safety/tolerability, pharmacokinetics, pharmacodynamics, and efficacy of our compound in vitro and in preclinical animal models. All current results indicate that Phototrexate is a drug candidate with high potential for development as an innovative light-regulated antifolate for cancer and psoriasis

¿Deben los modelos de emergencia de Lolium rigidum adaptarse en función de las condiciones climáticas?

Lolium rigidum es una problemática mala hierba a nivel mundial que en España produce importantes pérdidas de cultivo y económicas. El grupo de Biología y Agroecología de Malas hierbas (BAMh) de la SEMh ha estudiado la emergencia de esta especie durante dos campañas, 2016-17 y 2017-18. Para ello, se estableció un experimento en 10 localidades con una población de L. rigidum recolectada en Cataluña y se realizó el seguimiento de su emergencia cada 2-7 días. La emergencia se parametrizó en función de registros de temperatura y humedad procedentes de un datalogger enterrado a 2 cm. Los resultados muestran que el uso de los grados térmicos horarios es suficiente para una correcta descripción de la emergencia, desechando la opción de aplicar los grados hidrotérmicos, más comunes en los modelos de malas hierbas de invierno. Sin embargo, la emergencia de esta población de L. rigidum fue diferente en el centro y noreste de España respecto al sur, sugiriendo un efecto ambiental debido a su adaptación climática. Por ello, se plantea la necesidad de incluir poblaciones locales con el fin de adaptar el modelo desarrollado en el presente trabajo para los biotipos climáticos existentesPublishe