Gobierno corporativo en la empresa familiar. Arquitecturas diseñadas para superar la crisis de la delegación

En la vida de toda empresa familiar se producen crisis sucesivas de crecimiento. Quizás la más difícil de superar sea la denominada “Crisis de Autonomía Gerencial”. Este trance, que muchas veces produce seria parálisis en el crecimiento de la firma y consecuentemente fuertes pérdidas de valor, se genera cuando la organización adopta evolutivamente una determinada estructura con el fin de adaptarse a los duros requerimientos que impone el crecimiento. Si la organización logra superarla, entonces la delegación se consolida y se abren las puertas para fortalecer un sano proceso de separación de propiedad y control. En este trabajo el autor propone, basándose en la observación de numerosos casos de la vida real, prácticas específicas de Gobierno Corporativo que unidas a las modernas técnicas de medición y creación de valor, faciliten el tránsito de esta dura etapa de las empresas familiares e impulsen su crecimiento.

Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer

BACKGROUND: The identification of molecular and genetic markers to predict or monitor the efficacy of bevacizumab (BV) represents a key issue in the treatment of metastatic colorectal cancer (mCRC). METHODS: Plasma levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble VEGF receptor 2 (sVEGFR-2) and thrombospondin-1 (TSP-1) were assessed by ELISA assay at different time points in a cohort of 25 patients enroled in a phase II trial of GONO-FOLFOXIRI plus BV as first-line treatment of mCRC. VEGF: -2578A/C, -1498C/T, -1154A/G, -634C/G and 936C/T; and VEGFR-2: -604A/G, +1192C/T and +1719A/T, polymorphisms were assessed in a total of 54 patients. RESULTS: Treatment with GONO-FOLFOXIRI plus BV determined a prolonged and significant reduction in plasma free, biologically active VEGF concentration. Interestingly, VEGF concentrations remained lower than at baseline also at the time of PD. Conversely, PlGF levels increased during the treatment if compared with baseline, suggesting a possible role in tumour resistance; moreover, sVEGFR-2 increased at the time of PD, as well as TSP-1. No association of assessed polymorphisms with outcome was found. CONCLUSION: Our study suggested the possible mechanisms of resistance to combined therapy in those patients with a progressive disease to be tested in ongoing phase III randomised studies

“El sacrificio de Isaac”: Motivos midrashicos en el romancero popular

Tras examinarse El sacrificio de Isaac, romance de la tradición judeo-española de Marruecos, se considera que es posible hablar de significativas huellas de literatura midráshica. Además de las correspondencias específicas entre los romances peninsulares y la tradición midráshica, se ha observado la tendencia a engrandecer al pasivo y tímido Isaac de la Escritura y convertirlo en figura heroica, joven de fuerte voluntad y muy dueño de su destino. After examining El sacrificio de Isaac, a romance from the Spanish-Jewish tradition of Marruecos, it is considered that it is possible to speak of relevant traces of midrashic literature in it. Besides the specific matches between the peninsular romances and the midrashic tradition, the tendency to enlarge the passive and shy Isaac of the Scriptures turning him into a heroic figure—a young man with a strong will and master of his destiny—is observed

RAS mutation prevalence among patients with metastatic colorectal cancer: A meta-analysis of real-world data

Aim: A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. Materials & methods: Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. Results: The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8-48.5%); ranging from 33.7% (95% CI: 28.4-39.3%) to 54.1% (95% CI: 51.7-56.5%) between sources. Conclusion: The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research. © 2017 Future Medicine Ltd

Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer

BACKGROUND: Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti-epidermal growth factor receptor (EGFR) therapy. Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy. METHODS: In this prospective-retrospective analysis, we assessed the efficacy and safety of panitumumab plus oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) as compared with FOLFOX4 alone, according to RAS (KRAS or NRAS) or BRAF mutation status. A total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2 had results for at least one of the following: KRAS exon 3 or 4; NRAS exon 2, 3, or 4; or BRAF exon 15. The overall rate of ascertainment of RAS status was 90%. RESULTS: Among 512 patients without RAS mutations, progression-free survival was 10.1 months with panitumumab-FOLFOX4 versus 7.9 months with FOLFOX4 alone (hazard ratio for progression or death with combination therapy, 0.72; 95% confidence interval [CI], 0.58 to 0.90; P = 0.004). Overall survival was 26.0 months in the panitumumab-FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group (hazard ratio for death, 0.78; 95% CI, 0.62 to 0.99; P = 0.04). A total of 108 patients (17%) with non-mutated KRAS exon 2 had other RAS mutations. These mutations were associated with inferior progression-free survival and overall survival with panitumumab-FOLFOX4 treatment, which was consistent with the findings in patients with KRAS mutations in exon 2. BRAF mutations were a negative prognostic factor. No new safety signals were identified. CONCLUSIONS: Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapy