Vascular Endothelial Growth Factor plus Epidermal Growth Factor Receptor Dual Targeted Therapy in Metastatic Colorectal Cancer: Synergy or Antagonism?

There has been an intensive effort to develop novel therapies for the treatment of metastatic colorectal cancer (mCRC). The anti-epidermal growth factor receptor (EGFR) antibodies panitumumab and cetuximab and the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab have demonstrated clinical efficacy and acceptable toxicity in the treatment of mCRC as single agents or in combination with chemotherapy. Recent clinical trials have explored the efficacy and safety of treatment regimens incorporating chemotherapy in combination with bevacizumab and either panitumumab or cetuximab in patients with mCRC. Results from the BOND-2 trial, which investigated cetuximab, bevacizumab, and chemotherapy in mCRC, provided support for this therapeutic approach. Two large randomized phase 3 trials were initiated to evaluate firstline treatment of mCRC. The Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) study investigated the efficacy and safety of oxaliplatin- or irinotecan-based chemotherapy and bevacizumab with or without panitumumab; CAIRO2 assessed the efficacy and safety of capecitabine/oxaliplatin and bevacizumab with or without cetuximab. In both trials, the combination of bevacizumab, an EGFR-specific antibody, and chemotherapy in first-line treatment of mCRC was associated with increased toxicity and no improvement in patient outcome. These results suggest that these specific combinations should not be used in first-line mCRC outside investigational studies

Annual Survey of Virginia Law: Civil Practice and Procedure

This article focuses on some of the recent developments in civil litigation from June 1, 1998 to May 30, 1999, that have been effected by the Virginia General Assembly and the Supreme Court of Virginia. Each numbered discussion section is organized by topic in alphabetical order. This article highlights legislation of general interest to civil practitioners and does not purport to be all inclusive. This article does not address criminal procedure

Red nuggets grow inside-out: evidence from gravitational lensing

We present a new sample of strong gravitational lens systems where both the foreground lenses and background sources are early-type galaxies. Using imaging from HST/ACS and Keck/NIRC2, we model the surface brightness distributions and show that the sources form a distinct population of massive, compact galaxies at redshifts $0.4 \lesssim z \lesssim 0.7$, lying systematically below the size-mass relation of the global elliptical galaxy population at those redshifts. These may therefore represent relics of high-redshift red nuggets or their partly-evolved descendants. We exploit the magnifying effect of lensing to investigate the structural properties, stellar masses and stellar populations of these objects with a view to understanding their evolution. We model these objects parametrically and find that they generally require two S\'ersic components to properly describe their light profiles, with one more spheroidal component alongside a more envelope-like component, which is slightly more extended though still compact. This is consistent with the hypothesis of the inside-out growth of these objects via minor mergers. We also find that the sources can be characterised by red-to-blue colour gradients as a function of radius which are stronger at low redshift -- indicative of ongoing accretion -- but that their environments generally appear consistent with that of the general elliptical galaxy population, contrary to recent suggestions that these objects are predominantly associated with clusters.Comment: 21 pages; accepted for publication in MNRA

1991 Convocation

Opening Selections: George Bizet, Henry Mancini Processional: Jean Joseph Mouret Welcome: Dr. John Peoples, Director, Fermi National Accelerator Laboratory; Dr. Stephanie Pace Marshall, Executive Director; Walter Lee, Student Council President Introductions: Dr. Stephanie Pace Marshall Musical Selection: Lew Pallack Keynote Speaker: Dr. Donald L. Correll, Associate Program Leader, Laser Programs, Lawrence Livermore National Laboratory Recessional: Rimsky-Korsako

Quantification and expert evaluation of evidence for chemopredictive biomarkers to personalize cancer treatment.

Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines. We focused on studies that investigated changes in gene or protein expression as predictors of drug sensitivity or resistance. We considered an evidence framework that ranked studies from high level I evidence for randomized controlled trials to low level IV evidence for pre-clinical studies and patient case studies.We found that further in-depth analysis will be required to explore methodological issues, inconsistencies between studies, and tumor specific effects present even within high evidence level studies. Some of these nuances will lend themselves to automation, others will require manual curation. However, the comprehensive cataloging and analysis of dispersed public data utilizing an evidence framework provides a high level perspective on clinical actionability of these protein biomarkers. This framework and perspective will ultimately facilitate clinical trial design as well as therapeutic decision-making for individual patients