Colorectal cancer (CRC) has become a highly relevant condition nowadays. In this respect, advances in the understanding of its molecular basis are key for an adequate management. From the time when the adenoma-carcinoma sequence was formulated as a carcinogenesis model to this day, when, among other things, three major carcinogenic pathways have been identified, the CRC concept has evolved from that of a single disease to the notion that each CRC is a differentiated condition in itself. The suppressor or chromosome instability pathway, the mutator or microsatellite instability pathway, and the methylator or CpG island methylation pathway allow various phenotypes to be identified within CRC. Similarly, the presence of different changes in certain genes confers several behaviors on CRC from both the prognostic and responsive standpoints to specific therapies. However, this apparent complexity does help develop the clinical management of this disease through the identification of novel, more specific therapy targets, and also markers for various behaviors within the condition, which will most likely lead us to an individualized management for these patients.La importancia que está adquiriendo el cáncer colorrectal (CCR) hoy en día es importantísima. En este sentido, los avances en el conocimiento de sus bases moleculares son esenciales para su adecuado manejo. Desde la formulación del modelo de carcinogénesis de la secuencia adenoma-carcinoma hasta hoy, en que, entre otros aspectos, se han identificado tres grandes vías de carcinogénesis, el concepto de CCR ha llegado a transformarse desde el de una enfermedad única a la idea de que cada CCR es una entidad diferenciada respecto al resto de CCR. La vía supresora o de la inestabilidad cromosómica, la vía mutadora o de la inestabilidad de microsatélites, y la vía metiladora o del fenotipo metilador de islas CpG, permiten identificar diferentes fenotipos dentro del CCR. De la misma forma, la presencia de diferentes alteraciones a nivel de determinados genes confiere a los CCR distintas conductas desde el punto de vista pronóstico, o de respuesta a terapias concretas. Sin embargo la aparente complejidad, no hace sino ayudar en el desarrollo del manejo clínico de esta enfermedad a través de la identificación de nuevas dianas terapéuticas más específicas, o también de marcadores que determinan diferentes comportamientos dentro de la misma entidad, conduciéndonos, muy probablemente, a un manejo individualizado de estos pacientes.

Colorectal cancer (CRC) has become a highly relevant condition nowadays.In this respect, advances in the understanding of its molecular basis are key for an adequate management.From the time when the adenoma-carcinoma sequence was formulated as a carcinogenesis model to this day, when, among other things, three major carcinogenic pathways have been identified, the CRC concept has evolved from that of a single disease to the notion that each CRC is a differentiated condition in itself.The suppressor or chromosome instability pathway, the mutator or microsatellite instability pathway, and the methylator or CpG island methylation pathway allow various phenotypes to be identified within CRC.Similarly, the presence of different changes in certain genes confers several behaviors on CRC from both the prognostic and responsive standpoints to specific therapies.However, this apparent complexity does help develop the clinical management of this disease through the identification of novel, more specific therapy targets, and also markers for various behaviors within the condition, which will most likely lead us to an individualized management for these patients.

Pazopanib (Votrient, GSK) is an indazolylpyrimidine second-generation adenosine triphosphate–competitive inhibitor of human vascular endothelial growth factor receptors (VEGFRs), pleteled derived growth factor receptors (PDGFRs), and KIT in the range of IC50 10–84 nM. Lower activity was detected against FGFR1, FGFR3, and CSF1R, followed by FGFR4, AURKA, RAF, MLK1, PTKS, and TAOK3 kinases, shown at about 10-fold and over the concentration inhibiting VEGFR2, against which the molecule was optimized. The Food and Drug Administration (FDA) granted approval in 2009 for the treatment of patients with advanced renal cell carcinoma (RCC). In 2012, the indication was extended to patients with advanced soft tissue sarcoma (STS) who had received prior chemotherapy. In 2010, the European Medicines Agency (EMA) granted conditional approval of pazopanib as first-line treatment monotherapy, or following cytokine therapy for advanced RCC. The initial safety profile of pazopanib in monotherapy was based on 977 oncologic patients, including 586 with RCC; a detailed profile was depicted in 435 RCC patients (290 exposed to 800 mg/d), which was characterized by diarrhea, hypertension, hair depigmentation, nausea, anorexia, and vomiting. The corresponding profile in STS included fatigue, diarrhea, nausea, weight loss, hypertension, decreased appetite, hair depigmentation, vomiting, tumor pain, dysgeusia, cephalea, musculoskeletal pain, myalgia, gastrointestinal pain, and dyspnea. Events of major relevance were hepatotoxicity, for which a black box warning was issued since first approval, cardiotoxicity signs, hemorrhage, arterial/venous thromboembolic event, thrombotic microangiopathy, gastrointestinal perforation/fistula, infection, impaired wound healing, and proteinuria. In the limited pediatric experience, the safety profile appears similar to adult STS patients, with the exception of growth plate abnormalities in the pediatric profile, a rare but relevant adverse event.

Production of lipase by three strains of Geotrichum candidum (DBM 4012, DBM 4013, DBM 4166) and one strain of Geotrichum ludwigii (DBM 48) in liquid medium was investigated under addition of olive oil, which has been used as activator of the activity. The activity of cell-bound and extracellular lipases was determined. The most remarkable growth of the cell biomass was also observed using a medium with peptone as a source of nitrogen. The highest specific activity of all activated lipases was found when the cell growth reached a constant level (stationary phase of growth). All activated lipases were used as biocatalysts of the hydrolytic resolution of racemic cis- or trans-isomers of 2-(4-methoxybenzyl)cyclohexyl acetates. Attention was paid to the stereochemical course of the reaction, i.e. to the determination of the optical purity of the products and, consequently, to the assignment of the absolute configuration and the determination of the conversion rate. The satisfactory results from the point of view of the chemical yields of the reaction and enantiomeric purity of the products were obtained when lipases from G. candidum DBM 4013 were used as biocatalysts of the hydrolysis of trans-isomer of 2-(4-methoxybenzyl)cyclohexyl acetate.

The importance of colorectal cancer (CRC) is increasing. A proportion show a hereditary component, as in Lynch syndrome and Familial Adenomatous Polyposis, and a recently defined entity as well, namely, Familial Colorectal Cancer type X. The high probability to develop CRC in these groups may, at the time of recognition, change surgical management, including its timing or even the surgical technique. In some cases prophylactic surgery can play an important role. The possibility of using tools that allow recognition of the aforementioned syndromes, including microsatellite instability, immunohistochemistry for DNA mismatch repair system proteins, and especially their mutations, is on the basis of therapeutic strategies that differ from those employed in sporadic CRC cases.

The importance of colorectal cancer (CRC) is increasing. A proportion show a hereditary component, as in Lynch syndrome and Familial Adenomatous Polyposis, and a recently defined entity as well, namely, Familial Colorectal Cancer type X. The high probability to develop CRC in these groups may, at the time of recognition, change surgical management, including its timing or even the surgical technique. In some cases prophylactic surgery can play an important role. The possibility of using tools that allow recognition of the aforementioned syndromes, including microsatellite instability, immunohistochemistry for DNA mismatch repair system proteins, and especially their mutations, is on the basis of therapeutic strategies that differ from those employed in sporadic CRC cases.

El tratamiento de pacientes pediátricos que de manera accidental ingieren cuerpos extraños es un reto para el médico general, pediatra, gastroenterólogo y endoscopista. La Asociación Americana del Centro de Control de Intoxicaciones reportó que 75% de más de 116,000 casos suceden en menores de 5 años (6 meses a 3 años) y 98% son accidentales. Principalmente: monedas, juguetes, partes de juguetes, pines, huesos, bolos de comida, joyería, imanes y baterías de botón.