Targeted therapies in the management of locally advanced and metastatic pancreatic cancer: a systematic review

Pancreatic cancer has a dismal prognosis particularly in patients presenting with unresectable tumors. We performed a bibliometric analysis of clinical trials for pancreatic cancer conducted between 2014-2016 focusing on patients that presented with unresectable (locally advanced or metastatic) tumors. We discuss a range of studies that employed FOLFIRINOX, the gemcitabine + nab-paclitaxel combination and studies that used molecularly-targeted therapy. Major areas of focus have been dual targeting of EGFR and VEGFR, immunotherapy or a multimodal approach – combining chemotherapy with radiotherapy. We also point out the need for molecular selection for low prevalence subtypes. Key insights sourced from these pivotal trials should improve clinical outcomes for this devastating cancer

Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFbeta cell cycle arrest

TGFbeta is critical to control hepatocyte proliferation by inducing G1-growth arrest through multiple pathways leading to inhibition of E2F transcription activity. The retinoblastoma protein pRb is a key controller of E2F activity and G1/S transition which can be inhibited in viral hepatitis. It is not known whether the impairment of pRb would alter the growth inhibitory potential of TGFbeta in disease. We asked how Rb-deficiency would affect responses to TGFbeta-induced cell cycle arrest.Publisher PDFPeer reviewe

Health effects in fish of long-term exposure to effluents from wastewater treatment works

The effects of simple mixtures of chemicals, with similar mechanisms of action, can be predicted using the concentration addition model (CA). The ability of this model to predict the estrogenic effects of more complex mixtures such as effluent discharges, however, has yet to be established. Effluents from 43 U.K. wastewater treatment works were analyzed for the presence of the principal estrogenic chemical contaminants, estradiol, estrone, ethinylestradiol, and nonylphenol. The measured concentrations were used to predict the estrogenic activity of each effluent, employing the model of CA, based on the relative potencies of the individual chemicals in an in vitro recombinant yeast estrogen screen (rYES) and a short-term (14-day) in vivo rainbow trout vitellogenin induction assay. Based on the measured concentrations of the four chemicals in the effluents and their relative potencies in each assay, the calculated in vitro and in vivo responses compared well and ranged between 3.5 and 87 ng/L of estradiol equivalents (E2 EQ) for the different effluents. In the rYES, however, the measured E2 EQ concentrations in the effluents ranged between 0.65 and 43 ng E2 EQ/L, and they varied against those predicted by the CA model. Deviations in the estimation of the estrogenic potency of the effluents by the CA model, compared with the measured responses in the rYES, are likely to have resulted from inaccuracies associated with the measurement of the chemicals in the extracts derived from the complex effluents. Such deviations could also result as a consequence of interactions between chemicals present in the extracts that disrupted the activation of the estrogen response elements in the rYES. E2 EQ concentrations derived from the vitellogenic response in fathead minnows exposed to a series of effluent dilutions were highly comparable with the E2 EQ concentrations derived from assessments of the estrogenic potency of these dilutions in the rYES. Together these data support the use of bioassays for determining the estrogenic potency of WwTW effluents, and they highlight the associated problems for modeling approaches that are reliant on measured concentrations of estrogenic chemicals

Sustainable risk management of emerging contaminants in municipal wastewaters

This article is available open access through the publisher’s website at the link below. Copyright @ 2009 The Royal Society.The presence of emerging contaminants in municipal wastewaters, particularly endocrine-disrupting compounds such as oestrogenic substances, has been the focus of much public concern and scientific attention in recent years. Due to the scientific uncertainty still surrounding their effects, the Precautionary Principle could be invoked for the interim management of potential risks. Therefore, precautionary prevention risk-management measures could be employed to reduce human exposure to the compounds of concern. Steroid oestrogens are generally recognized as the most significant oestrogenically active substances in domestic sewage effluent. As a result, the UK Environment Agency has championed a ‘Demonstration Programme’ to investigate the potential for removal of steroid oestrogens and alkylphenol ethoxylates during sewage treatment. Ecological and human health risks are interdependent, and ecological injuries may result in increased human exposures to contaminants or other stressors. In this context of limiting exposure to potential contaminants, examining the relative contribution of various compounds and pathways should be taken into account when identifying effective risk-management measures. In addition, the explicit use of ecological objectives within the scope of the implementation of the EU Water Framework Directive poses new challenges and necessitates the development of ecosystem-based decision tools. This paper addresses some of these issues and proposes a species sensitivity distribution approach to support the decision-making process related to the need and implications of sewage treatment work upgrade as risk-management measures to the presence of oestrogenic compounds in sewage effluent

Teaching across disciplines: a case study of a project-based short course to teach holistic coastal adaptation design

Climate change has led to the need for innovation in resilient infrastructure and the social policies which will support those. This requires greater interdisciplinary interactions and knowledge building among emerging professionals. This paper presents a case study of a pilot short course intended to immerse graduate students in the design of resilient infrastructure using place-based and interdisciplinary active team learning. This course helps graduate students bridge the gap between research and practice on the social science and engineering of resilient infrastructure for coastal adaptation. The intellectual framework for the course (the Adaptive Gradients Framework) provides a holistic evaluation of adaptation design proposals and was used to recognize the complexity of social, ecological and engineering aspects and varied social benefits. The course provides a model to move outside rigid boundaries of institutions and disciplines to begin to build, in both students and instructors, the ability to work more effectively on complex social-ecological-engineering problems. Finally, this paper presents a summary of lessons learned from this pilot short course

Bovine leukemia virus non-productive infection of human mammary epithelial cells (MCF10A)

Bovine leukemia virus (BLV) is a retrovirus that causes lymphosarcoma in cattle. Some researchers suggestthat BLV could be related to breast cancer development, however, evidence that the virus can infect thehuman counterpart is lacking. For that reason, the objective of this study was to infect in vitro a humanmammary epithelial cell line (MCF10A) with BLV. The results suggest that the infection is non-productive,since only a fragment of the viral gene pol was detected in the cellular DNA. These results are consistentwith previous studies, where fragments of different BLV genes were found in human mammary tissue.Future studies should investigate whether this non-productive infection can be associated with human breastcancer.Fil: Martinez Cuesta, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Lendez, Pamela Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Sheahan, Maureen A.. Kansas State University; Estados UnidosFil: Rowland, Raymond R. R.. Kansas State University; Estados UnidosFil: Nieto Farías, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Dolcini, Guillermina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Ceriani, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentin