Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

New CC0\pi\ GENIE Model Tune for MicroBooNE

A novel tune has been made for the MicroBooNE experiment. The fit uses 4 new parameters within the GENIE v3.0.6 Monte Carlo program. Charged current pionless data from the T2K experiment was used. New uncertainties were obtained. These results will be used in future MicroBooNE analyses.Comment: 24 pages, 14 figure

First Measurement of Differential Charged Current Quasielasticlike νμ-Argon Scattering Cross Sections with the MicroBooNE Detector

We report on the first measurement of flux-integrated single differential cross sections for chargedcurrent (CC) muon neutrino (νμ) scattering on argon with a muon and a proton in the final state, 40Ar ðνμ; μpÞX. The measurement was carried out using the Booster Neutrino Beam at Fermi National Accelerator Laboratory and the MicroBooNE liquid argon time projection chamber detector with an exposure of 4.59 × 1019 protons on target. Events are selected to enhance the contribution of CC quasielastic (CCQE) interactions. The data are reported in terms of a total cross section as well as single differential cross sections in final state muon and proton kinematics.We measure the integrated per-nucleus CCQE-like cross section (i.e., for interactions leading to a muon, one proton, and no pions above detection threshold) of ð4.93 0.76stat 1.29sysÞ × 10−38 cm2, in good agreement with theoretical calculations. The single differential cross sections are also in overall good agreement with theoretical predictions, except at very forward muon scattering angles that correspond to low-momentum-transfer events.United States Department of Energy (DOE)National Science Foundation (NSF)Swiss National Science Foundation (SNSF)Science and Technology Facilities Council (STFC), part of the United Kingdom Research and InnovationRoyal Society of LondonAlbert Einstein Center for Fundamental Physics, Bern, SwitzerlandAzrieli FoundationZuckerman STEM Leadership ProgramIsrael Science FoundationVisiting Scholars Award Program of the Universities Research AssociationDE-AC02-07CH1135