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El cambio climático constituye una amenaza para la biodiversidad. La distribución geográfica y la dimensión de sus efectos sobre los individuos y ecosistemas son inciertas, siendo los montañosos los más sensibles al clima. En la presente investigación se determinó el área climática potencial adecuada para Phlegmariurus acerosus, P. taxifolius y P. reflexus, especies que habitan en bosques subtropicales húmedos y muy húmedos y ostentan alguna categoría de amenaza debido a la fragmentación del hábitat y la disminución continua de sus poblaciones. Se elaboraron modelos de nicho climático con el programa MaxEnt empleando datos de ocurrencia y variables bioclimáticas. Los modelos resultantes fueron proyectados geográficamente de acuerdo con las condiciones climáticas actuales. Las proyecciones evidenciaron que las condiciones climáticas adecuadas para las especies se distribuyen en las montañas de Cuba oriental. El nicho climático potencial tuvo una probabilidad de presencia alta, así: de 250,66 km2 para P. acerosus, 393,42 km2 para P. taxifolius, y 232,40 km2 para P. reflexus. Las áreas protegidas consideradas prioritarias para la conservación son nueve para P. acerosus y P. reflexus, y cinco para P. taxifolius. Las proyecciones realizadas se determinaron a partir de la elevación y la temperatura estacional. A su vez, las áreas prioritarias para la conservación de las especies correspondieron a las áreas protegidas en los macizos montañosos de Nipe-Sagua-Baracoa y la Sierra Maestra, siendo este último el de mayor importancia para los taxones.

We aimed to identify and validate a set of miRNAs that could serve as a prognostic signature useful to determine the recurrence risk for patients with COAD. Small RNAs from tumors of 100 stage II, untreated, MSS colon cancer patients were sequenced for the discovery step. For this purpose, we built an miRNA score using an elastic net Cox regression model based on the disease-free survival status. Patients were grouped into high or low recurrence risk categories based on the median value of the score. We then validated these results in an independent sample of stage II microsatellite stable tumor tissues, with a hazard ratio of 3.24, (CI95% = 1.05–10.0) and a 10-year area under the receiver operating characteristic curve of 0.67. Functional analysis of the miRNAs present in the signature identified key pathways in cancer progression. In conclusion, the proposed signature of 12 miRNAs can contribute to improving the prediction of disease relapse in patients with stage II MSS colorectal cancer, and might be useful in deciding which patients may benefit from adjuvant chemotherapy.

DNA methylation biomarkers for noninvasive diagnosis of colorectal cancer (CRC) and precursor lesions have been extensively studied. Different panels have been reported attempting to improve current protocols in clinical practice, although no definite biomarkers have been established.In the present study, we have examined patient biopsies starting from a comprehensive analysis of DNA methylation differences between paired normal and tumor samples in known cancer-related genes aiming to select the best performing candidates informative for CRC diagnosis in stool samples.Five selected markers were considered for subsequent analyses in independent biologic cohorts and in silico data sets. Among the five selected genes, three of them (AGTR1, WNT2 and SLIT2) were validated in stool DNA of affected patients with a detection sensitivity of 78% [95% confidence interval (CI), 56%–89%]. As a reference, DNA methylation of VIM and SEPT9 was evaluated in a subset of stool samples yielding sensitivities of 55% and 20%, respectively. Moreover, our panel may complement histologic and endoscopic diagnosis of inflammatory bowel disease (IBD)-associated neoplasia, as it was also efficient detecting aberrant DNA methylation in non-neoplastic tissue samples from affected patients.This novel panel of specific methylation markers can be useful for early diagnosis of CRC using stool DNA and may help in the follow-up of high-risk patients with IBD. Cancer Prev Res; 6(7); 656–65. ©2013 AACR.

PDF File - 916K, Representative pyrograms in a healthy colonic mucosa sample for the markers analyzed.

PDF file - 574K, Microarray pre-processing.

List of all SNVs found

Purpose: Epithelial ovarian cancer (EOC) is the fifth leading cause of death in women diagnosed with gynecologic malignancies. The low survival rate is because of its advanced-stage diagnosis and either intrinsic or acquired resistance to standard platinum-based chemotherapy. So, the development of effective innovative therapeutic strategies to overcome cisplatin resistance remains a high priority.Experimental Design: To investigate new treatments in in vivo models reproducing EOCs tumor growth, we generated a preclinical model of ovarian cancer after orthotopic implantation of a primary serous tumor in nude mice. Further, matched model of acquired cisplatin-resistant tumor version was successfully derived in mice. Effectiveness of lurbinectedin (PM01183) treatment, a novel marine-derived DNA minor groove covalent binder, was assessed in both preclinical models as a single and a combined-cisplatin agent.Results: Orthotopically perpetuated tumor grafts mimic the histopathological characteristics of primary patients' tumors and they also recapitulate in mice characteristic features of tumor response to cisplatin treatments. We showed that single lurbinectedin or cisplatin-combined therapies were effective in treating cisplatin-sensitive and cisplatin-resistant preclinical ovarian tumor models. Furthermore, the strongest in vivo synergistic effect was observed for combined treatments, especially in cisplatin-resistant tumors. Lurbinectedin tumor growth inhibition was associated with reduced proliferation, increased rate of aberrant mitosis, and subsequent induced apoptosis.Conclusions: Taken together, preclinical orthotopic ovarian tumor grafts are useful tools for drug development, providing hard evidence that lurbinectedin might be a useful therapy in the treatment of EOC by overcoming cisplatin resistance. Clin Cancer Res; 18(19); 5399–411. ©2012 AACR.

List of primers used in Sanger sequencing and SNPs utilized to genotype the 84 normal adjacent and tumor samples.

List of recurrent mutated genes ranked by MutSig tool.

supplementary material legends (tables and figures)

Baseline characteristics of CRC patients (discovery dataset, Sanger validation dataset and TCGA datasets).

Supplementary Figures (1 to 15)

PDF file, 282K, Presence of aberrant mitotic figures in engrafted OVA1X tumors analyzed by co-immunostaining with anti-H3S10ph, anti-tubulin. Chromosomes were labeled with DAPI.

Mutations validated in Biomark platform (Fluidigm) and by Sanger Sequencing.

PDF file, 80K, Extensive histopathologic regression criteria analysis in post-chemotherapy engarfted OVA1X tumor.

List of recurrent mutations

List of statistically significant functions in which mutated genes are implicated.

Mutations found in AMER1 gene across different datasets

In May 1982, the US Food and Drug Administration (FDA) approved the use of streptozotocin to treat pancreatic neuroendocrine tumors (panNETs). Thus, this year marks 40 years since that landmark date. This review of streptozotocin to treat panNETs is intended to commemorate this anniversary. A historical perspective of the chemical structure, pharmacokinetics, and mechanism of action of streptozotocin is followed by data from prospective and retrospective clinical studies. The last section of the review addresses the latest aspects and takes note of the prospects that lie ahead on the future horizon of the use of streptozotocin to treat panNETs, including ongoing clinical trials.

Crossover can bias clinical outcomes of randomized clinical trials by increasing the risk of both type I (false positive) and type II (false negative) errors. To show how crossover can increase type I error, we provide computer simulation and review herein illustrative examples (iniparib, olaratumab) of recently reported RCTs that demonstrated false-positive treatment efficacy signals due to crossover. The ethical issues associated with crossover are also discussed.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress-response programs that counteract the inherent toxicity of such aberrant signaling. While inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of Protein Phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumorsin vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumorsin vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor suppressive resistance.

ObjectivesMultidisciplinary teams in cancer care are increasingly using information and communication technology (ICT), hospital health information system (HIS) functionalities and ICT-driven care components. We aimed to explore the use of these tools in multidisciplinary team meetings (MTMs) and to identify the critical challenges posed by their adoption based on the perspective of professionals representatives from European scientific societies.DesignThis qualitative study used discussion of cases and focus group technique to generate data. Thematic analysis was applied.SettingHealthcare professionals working in a multidisciplinary cancer care environment.ParticipantsSelection of informants was carried out by European scientific societies in accordance with professionals’ degree of experience in adopting the implementation of ICT and from different health systems.ResultsProfessionals representatives of 9 European scientific societies were involved. Up to 10 ICTs, HIS functionalities and care components are embedded in the informational and decision-making processes along three stages of MTMs. ICTs play a key role in opening MTMs to other institutions (eg, by means of molecular tumour boards) and information types (eg, patient-reported outcome measures), and in contributing to the internal efficiency of teams. While ICTs and care components have their own challenges, the information technology context is characterised by the massive generation of unstructured data, the lack of interoperability between systems from different hospitals and HIS that are conceived to store and classify information rather than to work with it.ConclusionsThe emergence of an MTM model that is better integrated in the wider health system context and incorporates inputs from patients and support systems make traditional meetings more dynamic and interconnected. Although these changes signal a second transition in the development process of multidisciplinary teams, they occur in a context marked by clear gaps between the information and management needs of MTMs and the adequacy of current HIS.

Description, The mTOR-LARP1-5′TOP axis acts at the translational level as a primary guardian of the anabolic capacity of the cell., Ribosomes execute the transcriptional program in every cell. Critical to sustain nearly all cellular activities, ribosome biogenesis requires the translation of ~200 factors of which 80 are ribosomal proteins (RPs). As ribosome synthesis depends on RP mRNA translation, a priority within the translatome architecture should exist to ensure the preservation of ribosome biogenesis capacity, particularly under adverse growth conditions. Here, we show that under critical metabolic constraints characterized by mTOR inhibition, LARP1 complexed with the 40S subunit protects from ribophagy the mRNAs regulon for ribosome biogenesis and protein synthesis, acutely preparing the translatome to promptly resume ribosomes production after growth conditions return permissive. Characterizing the LARP1-protected translatome revealed a set of 5′TOP transcript isoforms other than RPs involved in energy production and in mitochondrial function, among other processes, indicating that the mTOR-LARP1-5′TOP axis acts at the translational level as a primary guardian of the cellular anabolic capacity.

Las personas, las familias, las organizaciones y los países son impactadas por el entorno actual existente esto es la globalización, la competencia, la sobrepoblación, los avances tecnológicos dificultando su adaptación adecuada a las circunstancias que el momento exigen originando un impacto en los comportamientos humanos.Lo anterior lleva por tanto al interés de analizar, reflexionar, investigar, observar y proponer nuevas herramientas, conocimientos, instrumentos y metodologías que permitan a las empresas mexicanas (sobre todo pequeñas y medianas) lograr una mayor eficiencia en los resultados obtenidos, así como mejorar las prácticas para adaptarse a los cambios que el entorno exige.El presente trabajo presenta los avances sobre un proyecto de investigación-acción con estudio de caso, cuyo objetivo es observar los impactos que el estrés tiene en una pequeña organización comercial mexicana y proponer acciones de ayuda para reducirlo en la vida de la organización, con la participación de nueve personas consideradas como claves (ejecutivos de la organización) integradas en tres equipos de trabajo con la finalidad de impulsar y promover una manera distinta de resolver los problemas identificados, mediante una metodología basada en un proceso de intervención. Se reportan los resultados obtenidos hasta el momento (80% de avance) destacándose los siguientes:- Abatimiento de los indicadores de puntualidad y asistencia de una manera significativa sin tener como prerrequisitos castigos o estímulos.- Integración de verdaderos equipos de trabajo cooperativos y colaborativos- Redefinición de procesos claves en la organización y en la toma de decisiones- Reducción de conflictos- Mejora del clima organizacional.

En la presente investigación se podrá analizar los diferentes retos y realidades que han tenido que vivir los empresarios caqueteños para estar a la vanguardia de las nuevas tecnologías y las TIC’S según una entrevista informal que se les realizo a cuatro exitosos empresarios de la región ven la inclusión digital para sus organizaciones como una oportunidad de innovación, con ello poder llamar la atención en el cliente ya que hoy por hoy ser eficiente y eficaz es una prioridad para toda empresa que quiera ser exitosa en el mercado.

The Peace Process brought forward between the Colombian government and the FARC-EP guerrilla group demanded a new understanding of the internal conflict that Colombia has been living in since the second half of the last century. Within the formative options that were pronounced on this political conjuncture, it is worth mentioning the non-formal education processes that arise within communities and which reflect the thematic and pedagogical interests of their participants. The Post-Conflict Diploma Course (Medellin, 2016) is a milestone in education for peace, as it was managed as part of the Local Planning and Participatory Budgeting Program, a democratic tool that allows communities to prioritize resources for intervention in their most pressing problems. This educational scenario was built on the guidelines of the SFCP, which is based on critical and social pedagogies, and on the approach of capability and skills development of the subjects in formation.

Characterization of hydrogen bonds in CH4-(H2O)12 clusters was carried out by using several quantum chemistry tools. An initial stochastic search provided around 2 500 000 candidate structures, then, using a convex-hull polygon criterion followed by gradient based optimization under the Kohn-Sham scheme, a total of 54 well defined local minima were located in the Potential Energy Surface. These structures were further analyzed through second-order many-body perturbation theory with an extended basis set at the MP2/6-311++G(d,p) level. Our analysis of Gibbs energies at several temperatures clearly suggests a structural preference toward compact water clusters interacting with the external methane molecule, instead of the more commonly known clathrate-like structures. This study shows that CH4-(H2O)12 clusters may be detected at temperatures up to 179 K, this finding provides strong support to a recently postulated hypothesis that suggests that methane-water clusters could be present in Mars at these conditions. Interestingly, we found that water to water hydrogen bonding is strengthened in the mixed clusters when compared to the isolated water dimer, which in turn leads to a weakening of the methane to water hydrogen bonding when compared to the CH4-(H2O) dimer. Finally, our evidence places a stern warning about the abilities of popular geometrical criteria to determine the existence of hydrogen bonds.

Undifferentiated large cell carcinoma is a rare entity in esophageal cancer and very few data are available in the literature on this uncommon histological subtype. We report a case of a 58-year-old Caucasian male previously treated with cisplatin/5-fluorouracil, docetaxel and carboplatin/plitidepsin who received treatment with a novel antitumor agent, Irvalec (PM02734), as fourth line. The patient received treatment from July 2006 to July 2009, a total of 49 cycles, at a dose of 2.4 mg/m 2 as a 24-hour infusion every 3 weeks. He did not present severe complications or unplanned or cumulative toxicities. Complete and durable response according to RECIST was reported. He was alive at the last follow-up on March 2012.

ENETS Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Neoplasms of the Digestive System : Well-Differentiated Pancreatic Non-Functioning Tumors

Colorectal cancer is the third most common malignant neoplasm and the second cause of death by cancer in western countries. In this manuscript, the clinical guidelines of the Spanish Society of Medical Oncology (SEOM) for diagnosis and adjuvant treatment of colon cancer and rectal cancer are reported.

La acción de un campo magnético sobre una sustancia crea efectos como el diamagnetismo, el paramagnetismo y el ferromagnetismo. En este artículo se explica, sucintamente, los efectos y la resonancia en la anatasa (TiO2) policristalina; asimismo se describe el proceso de obtención y las características de esta sustancia.

OBJETIVO.- Evaluar la eficacia del misoprostol en aborto frusto y gestación anembrionada comparando la vía de administración vaginal-oral y vaginal sublingual. MATERIAL Y MÉTODO.-El diseño de estudio corresponde a un estudio descriptivo. La muestra de estudio estuvo conformado por todas las pacientes en el primer trimestre de gestación, atendidas en el Servicio de Obstetricia del Hospital Nacional Sergio Bernales entre Enero y Diciembre del 2009. En total fueron 230 pacientes que cumplieron los criterios de inclusión. Se utilizó un formulario para consolidar los datos recogidos de las historias clínicas. El formulario se elaboró teniendo en consideración los objetivos del estudio. Se acudió al área de estadística del INEN para obtener la lista de pacientes que recibieron misoprostol en el año 2009. Se coordinó con el Archivo de Historias Clínicas para la obtención de las historias seleccionadas para el estudio. RESULTADOS.- De los 230 casos estudiados, 65.2% correspondieron A aborto frustro (150 casos) y 34.8% corresponden (80 casos) en gestación anembrionada. CONCLUSIONES.-De acuerdo a los objetivos se concluye que el tiempo de evacuación se presentó en un mayor porcentaje (66.7%) en un tiempo de 6 horas en aborto frustro, lo mismo que para la gestación anembrionada en (68.1%). Entre las complicaciones más frecuentes encontradas tenemos las deposiciones líquidas 23.3% (35 casos) en aborto frustro y 22.5% (18 casos) en gestación anembrionada y en menor caso tenemos fiebre y vómitos en cada grupo. La dosis con la que se obtuvo una mayor eficacia (maduración cervical 8 mm) fue la vía fondo de saco vaginal mas vía oral en dosis de 200 ug + 600 ug. obteniéndose un 60% de eficacia para el aborto frustro y un 56.25% para gestación anembrionada.

Este documento de consenso nace como una iniciativa conjunta de la Sociedad Española de Anatomía Patológica (SEAP) y de la Sociedad Española de Oncología Médica (SEOM) y propone recomendaciones diagnósticas y terapéuticas para el manejo del paciente con cáncer colorrectal (CCR) hereditario, localizado y avanzado basadas en la evidencia científica que existe en la actualidad sobre el uso de biomarcadores. Por tanto, este documento supone una oportunidad para mejorar la eficiencia de la actividad asistencial y la utilización de recursos, lo que redundará en un beneficio para estos pacientes. Con los datos disponibles en la actualidad, este grupo de expertos recomienda que en los pacientes con CCR localizado se determine la inestabilidad de microsatélites, ya que es un factor predictivo relevante para decidir el tratamiento adyuvante. Sin embargo, aunque las firmas de expresión genética ColoPrint® y Oncotype Dx® han demostrado tener valor pronóstico, no existe todavía consenso sobre su uso en la práctica clínica. En cuanto al CCR avanzado, la determinación del estado mutacional de KRAS es indispensable antes de administrar un tratamiento con anti-receptor del factor de crecimiento epidérmico (EGFR), como cetuximab y panitumumab. Sin embargo, la determinación de otros biomarcadores, como las mutaciones de BRAF, EGFR, PI3K y PTEN, no debe llevarse a cabo de forma rutinaria, ya que hoy por hoy no influye en la planificación del tratamiento. Otros aspectos importantes que incluye son los requisitos organizativos y los controles de calidad que deben existir para la adecuada determinación de estos biomarcadores, así como las implicaciones legales que se deben tener en cuenta.

Resumen La elevada frecuencia de recidivas tumorales en el cancer colorrectal hace que, al evaluar sus posibilidades terapeuticas quirurgicas, se efectuen estudios (eco/TAC/RMN) capaces de determinar el grado de diseminacion de la enfermedad. La tomografia de emision de positrones (PET) permite una mejor estadificacion de la extension de la recidiva metastasica, tal como se demuestra en los dos casos que presentamos (uno con una segunda recidiva ganglionar mesenterica y otro con recidiva exclusivamente hepatica), lo que permitio en ambos casos una exeresis de dicha recidiva con caracter radical. Queda por definir el impacto de la PET sobre los resultados de esta cirugia de rescate en el cancer colorrectal.

BACKGROUND α-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) closely follow the course of germ cell tumors (GCTs) and are widely used for diagnosis, prognosis, and follow-up purposes. The objective of this study was to assess the concordance of tumor markers at the time of diagnosis and recurrence. METHODS The authors reviewed the records of 794 patients with GCTs treated in three Spanish hospitals from 1977–1996 and analyzed the concordance between AFP, HCG, and LDH levels at diagnosis and first and second recurrence. A positive marker was defined as a level of AFP > 10 ng/mL, HCG > 5 IU/L, or LDH > the upper limit of normal. One hundred twenty-five patients were identified who developed a first recurrence (123 had marker levels recorded). The median age was 27 years (range, 14–78 years). Histology was seminoma in 36 patients (29%) and nonseminomatous GCT (NSGCT) in 87 patients (71%). RESULTS Seventy-nine patients (64%) had elevated tumor markers at diagnosis and 76 (62%) at first recurrence. An elevated marker was present at first recurrence in 58 of 79 patients (73%) with initially positive markers and in 18 of 44 patients (41%) with initially negative markers. In 84 of 123 patients (68%), the same marker pattern (positive or negative) was present at the time of diagnosis and at first recurrence, 78% in seminomas and 64% in NSGCTs. The earliest indicator of recurrence was an elevated marker in patients with NSGCTs and a radiologic finding in patients with seminomas. Thirty patients developed a second recurrence, 27 of whom (90%) had the same marker pattern as at first recurrence. CONCLUSIONS Tumor marker pattern at diagnosis is not a good predictor of the pattern at recurrence, particularly in patients with NSGCTs. Marker assessment should be included in the follow-up schedule regardless of levels at the time of diagnosis. Early detection of recurrence should not rely only on marker levels, even in patients with elevated levels at presentation. Cancer 2000;88:162–8. © 2000 American Cancer Society.

KRAS mutations contribute to cell proliferation and survival in numerous cancers, including colorectal cancers (CRC). One pathway through which mutant KRAS acts is an inflammatory pathway that involves the kinase IKK and activates the transcription factor NF-κB. BRAF, a kinase that is downstream of KRAS, is mutated in a subset of CRC and is predictive of poor prognosis and therapeutic resistance. We found that, in contrast to mutant KRAS, mutant BRAF (BRAF(V600E)) did not trigger NF-κB activation but instead triggered the phosphorylation of a proteolytic fragment of IKKα (p45-IKKα) in CRC cells. BRAF(V600E) CRC cells had a high abundance of phosphorylated p45-IKKα, which was decreased by a RAF inhibitor. However, the abundance and DNA binding of NF-κB in these cells were unaffected by the RAF inhibitor, and expression of BRAF(V600E) in human embryonic kidney-293T cells did not activate an NF-κB reporter. Moreover, BRAF-induced transformation of NIH-3T3 cells and BRAF-dependent transcription required phosphorylation of p45-IKKα. The kinase TAK1, which was associated with the endosomal compartment, phosphorylated p45-IKKα. Inhibition of endosomal vacuolar adenosine triphosphatase (V-ATPase) with chloroquine or bafilomycin A1 blocked p45-IKKα phosphorylation and induced apoptosis in BRAF-mutant CRC cells independent of autophagy. Treating mice with V-ATPase inhibitors reduced the growth and metastasis of BRAF(V600E) xenograft tumors in the cecum of mice. Funding: P.M. is a recipient of a Formación de Profesorado Universitario (FPU) fellowship (AP2009-2892), and L.E. is an investigator at the Carlos III program. This work was further supported by Instituto de Salud Carlos III-FEDER grants PI13/00448, AGAUR (SGR23), and RTICCS/FEDER (RD12/0036/0054 and RD09/0076/00036) and “Xarxa de Bancs de tumors” sponsored by the Pla Director d’Oncologia de Catalunya (XBTC).