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https://www.readbyqxmd.com/read/28731945/the-changing-paradigm-of-radiotherapy-in-the-elderly-population
#1
Myer Raphael Pfeffer, Philip Blumenfeld
There is increasing awareness of the special needs for care of the elderly cancer patient. Newer precise conformal radiotherapy techniques allow the safe delivery of higher doses of radiotherapy to the target tumor while reducing the dose to surrounding critical organs. This has led to a shortening of radiotherapy protocols for both curative and palliative indications. We review these novel techniques and protocols and the published clinical studies that include elderly patients treated with these techniques...
July 2017: Cancer Journal
https://www.readbyqxmd.com/read/28731221/evaluating-the-renal-safety-of-investigational-new-drugs-where-should-we-be-going
#2
N Stockbridge, M Blank, E A Hausner, A Thompson
We the authors work in the US Food and Drug Administration (FDA) review division responsible for the therapeutic agents for primary renal disease. We also field consultative inquiries regarding off-target adverse renal effects of drugs intended to treat other diseases. We do neither basic science research on renal diseases nor clinical studies of new drugs, but we are professional spectators of both. We offer here our thoughts on the challenge of identifying renal safety signals in the preclinical space and in the earliest phases of clinical development...
July 21, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28730075/ccr7-p-erk1-2-vegf-signaling-promotes-retinal-neovascularization-in-a-mouse-model-of-oxygen-induced-retinopathy
#3
Lin-Hui Yuan, Xiao-Long Chen, Yu Di, Mei-Lin Liu
AIM: To investigate the role of CCR7/p-ERK1/2/VEGF signaling in the mouse model of oxygen-induced retinopathy (OIR). METHODS: Neonatal C57BL/6J mice were evenly randomized into four groups: normoxia, OIR, OIR control (treated with scramble siRNA), and OIR treated (treated with CCR7 siRNA). Normoxia group was not specially handled. Postnatal day 7 (P7) mice in the OIR group were exposed to 75%±5% oxygen for 5d (P7-P12) and then maintained under normoxic conditions for 5d (P12-P17)...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28729428/fluorine-18-labeled-carboplatin-derivative-for-pet-imaging-of-platinum-drug-distribution
#4
Narottam Lamichhane, Gajanan K Dewkar, Sundaresan Gobalakrishnan, Li Wang, Purnima Jose, Muhammad Otabashi, Jean-Luc Morelle, Nicholas Farrell, Jamal Zweit
Increasing evidence indicates that reduced intracellular drug accumulation is the parameter most consistently associated with platinum drug resistance, and emphasizes the need to directly measure intra-tumor drug concentration. In the era of precision medicine and with the advent of powerful imaging and proteomics technologies, there is an opportunity to better understand drug resistance, by exploiting these techniques to provide new knowledge on drug-target interactions. Here, we are contributing to this endeavor by reporting on the development of a fluorine-18 labeled carboplatin derivative ((18)F-FCP) that can be used to potentially image drug uptake and retention, including intra-tumoral distribution, by positron emission tomography (PET)...
July 20, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28729250/stellarex-drug-coated-balloon-for-treatment-of-femoropopliteal-disease-12-month-outcomes-from-the-randomized-illumenate-pivotal-and-pharmacokinetic-studies
#5
Prakash Krishnan, Peter Faries, Khusrow Niazi, Ash Jain, Ravish Sachar, William B Bachinsky, Joseph A Cardenas, Martin Werner, Marianne Brodmann, J A Mustapha, Carlos I Mena-Hurtado, Michael R Jaff, Andrew H Holden, Sean P Lyden
Background -Drug-coated balloons (DCB) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease. Due to differences in excipients, paclitaxel dose and coating morphologies, varying clinical outcomes have been observed with different DCBs. We report the results of two studies investigating the pharmacokinetic (PK) and clinical outcomes of a new DCB to treat femoropopliteal disease. Methods -In the ILLUMENATE Pivotal Study, 300 symptomatic patients (Rutherford class 2-4), were randomized to DCB (N=200) or standard angioplasty (PTA) (N=100)...
July 20, 2017: Circulation
https://www.readbyqxmd.com/read/28729159/what-do-we-know-about-laminar-connectivity
#6
REVIEW
Kathleen S Rockland
In this brief review, I attempt an overview of the main components of anatomical laminar-level connectivity. These are: extrinsic outputs, excitatory and inhibitory intrinsic connectivity, and intrinsic inputs. Supporting data are biased from the visual system of nonhuman primates (NHPs), but I have drawn as much as possible from a broader span in order to treat the important issue of area-specific variability. In a second part, I briefly discuss laminar connectivity in the context of network organization (feedforward/feedback cortical connections, and the major types of corticothalamic connections)...
July 17, 2017: NeuroImage
https://www.readbyqxmd.com/read/28728604/target-d-a-stratified-individually-randomized-controlled-trial-of-the-diamond-clinical-prediction-tool-to-triage-and-target-treatment-for-depressive-symptoms-in-general-practice-study-protocol-for-a-randomized-controlled-trial
#7
Jane Gunn, Caroline Wachtler, Susan Fletcher, Sandra Davidson, Cathrine Mihalopoulos, Victoria Palmer, Kelsey Hegarty, Amy Coe, Elizabeth Murray, Christopher Dowrick, Gavin Andrews, Patty Chondros
BACKGROUND: Depression is a highly prevalent and costly disorder. Effective treatments are available but are not always delivered to the right person at the right time, with both under- and over-treatment a problem. Up to half the patients presenting to general practice report symptoms of depression, but general practitioners have no systematic way of efficiently identifying level of need and allocating treatment accordingly. Therefore, our team developed a new clinical prediction tool (CPT) to assist with this task...
July 20, 2017: Trials
https://www.readbyqxmd.com/read/28728419/apoferritin-nanocage-for-brain-targeted-doxorubicin-delivery
#8
Zhijiang Chen, Meifang Zhai, Xiang Yang Xie, Yue Zhang, Siyu Ma, Zhiping Li, Fanglin Yu, Baoquan Zhao, Min Zhang, Yang Yang, Xingguo Mei
An ideal brain-targeted nanocarrier must be sufficiently potent to penetrate the blood-brain barrier (BBB) and sufficiently competent to target the cells of interest with adequate optimized physiochemical features and biocompatibility. However, it is an enormous challenge to the researchers to organize the abovementioned properties into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials. Herein, we demonstrate a straightforward strategy for brain targeting by encapsulating doxorubicin (DOX) into a naturally available and unmodified apoferritin nanocage (DOX-loaded APO)...
July 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28728415/-177-lu-labelled-cyclic-minigastrin-analogues-with-therapeutic-activity-in-cck2r-expressing-tumours-preclinical-evaluation-of-a-kit-formulation
#9
Christine Rangger, Maximilian Klingler, Lajos Balogh, Zita Pöstényi, Andras Polyak, Dariusz Pawlak, Renata Mikołajczak, Elisabeth von Guggenberg
Minigastrin (MG) analogues specifically target cholecystokinin-2 receptors (CCK2R) expressed in different tumours and enable targeted radiotherapy of advanced and disseminated disease when radiolabelled with a beta emitter such as (177)Lu. Especially truncated MG analogues missing the penta-Glu sequence are associated with low kidney retention and seem therefore most promising for therapeutic use. Based on [D-Glu1,desGlu2-6]MG (MG11) we have designed the two cyclic MG analogues cyclo1,9[γ-D-Glu1,desGlu2-6,D-Lys9]MG (cyclo-MG1) and cyclo1,9[γ-D-Glu1,desGlu2-6,D-Lys9,Nle11]MG (cyclo-MG2)...
July 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28727604/preclinical-development-of-ebi-005-an-il-1-receptor-1-inhibitor-for-the-topical-ocular-treatment-of-ocular-surface-inflammatory-diseases
#10
Joseph Kovalchin, Bracken King, Allyson Masci, Elizabeth Hopkins, Jeremy Fry, Jay Hou, Christian Li, Kelly Tenneson, Steve Weber, Gary Wolfe, Kathy Collins, Eric S Furfine
OBJECTIVE: Topical interleukin (IL)-1 receptor (R)1 blockade is therapeutically active in reducing signs and symptoms of dry eye disease. Herein, we describe in vitro and in vivo nonclinical Investigational New Drug (IND)-enabling studies of EBI-005, a novel protein chimera of IL-1β and IL-1 receptor antagonist (IL-1Ra or anakinra) that potently binds IL-1R1 and blocks signaling. These studies provide an assessment of receptor affinity, drug bioavailability, immunogenic response, safety, and tolerability in mice and rabbits...
July 18, 2017: Eye & Contact Lens
https://www.readbyqxmd.com/read/28727445/an-antibiotic-that-inhibits-the-atpase-activity-of-an-abc-transporter-by-binding-to-a-remote-extracellular-site
#11
Leigh Morgan Matano, Heidi Gabrielle Morris, Anthony R Hesser, Sara E S Martin, Wonsik Lee, Tristan W Owens, Emaline Laney, Hidemasa Nakaminami, David Hooper, Timothy C Meredith, Suzanne Walker
Antibiotic-resistant strains of Staphylococcus aureus pose a major threat to human health and there is an ongoing need for new antibiotics to treat resistant infections. In a high throughput screen (HTS) of 230,000 small molecules designed to identify bioactive wall teichoic acid (WTA) inhibitors, we identified one hit, which was expanded through chemical synthesis into a small panel of potent compounds. We showed that these compounds target TarG, the transmembrane component of the two-component ATP-binding cassette (ABC) transporter TarGH, which exports WTA precursors to the cell surface for attachment to peptidoglycan...
July 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28726132/phase-i-dose-escalation-study-of-nms-1286937-an-orally-available-polo-like-kinase-1-inhibitor-in-patients-with-advanced-or-metastatic-solid-tumors
#12
Glen J Weiss, Gayle Jameson, Daniel D Von Hoff, Barbara Valsasina, Cristina Davite, Claudia Di Giulio, Francesco Fiorentini, Rachele Alzani, Patrizia Carpinelli, Alessandro Di Sanzo, Arturo Galvani, Antonella Isacchi, Ramesh K Ramanathan
Background Pharmacological inhibition of polo-like kinase 1 (PLK1) represents a new approach for the treatment of solid tumors. This study was aimed at determining the first cycle dose-limiting toxicities (DLTs) and related maximum tolerated dose (MTD) of NMS-1286937, a selective ATP-competitive PLK1-specific inhibitor. Secondary objectives included evaluation of its safety and pharmacokinetic (PK) profile in plasma, its antitumor activity, and its ability to modulate intracellular targets in biopsied tissue...
July 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28725925/characterisation-of-peptide5-systemic-administration-for-treating-traumatic-spinal-cord-injured-rats
#13
Yilin Mao, Tara Nguyen, Ryan S Tonkin, Justin G Lees, Caitlyn Warren, Simon J O'Carroll, Louise F B Nicholson, Colin R Green, Gila Moalem-Taylor, Catherine A Gorrie
Systemic administration of a Connexin43 mimetic peptide, Peptide5, has been shown to reduce secondary tissue damage and improve functional recovery after spinal cord injury (SCI). This study investigated safety measures and potential off-target effects of Peptide5 systemic administration. Rats were subjected to a mild contusion SCI using the New York University impactor. One cohort was injected intraperitoneally with a single dose of fluorescently labelled Peptide5 and euthanised at 2 or 4 h post-injury for peptide distribution analysis...
July 19, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28725431/angiosarcoma-treated-successfully-with-anti-pd-1-therapy-a-case-report
#14
Simran Sindhu, Lana H Gimber, Lee Cranmer, Ali McBride, Andrew S Kraft
BACKGROUND: Angiosarcomas are tumors of malignant endothelial origin that have a poor prognosis with a five-year survival of less than 40%. These tumors can be found in all age groups, but are more common in older patients; with the cutaneous form most common in older white men. Combined modality therapy including surgery and radiation appears to have a better outcome than each modality alone. When metastatic, agents such as liposomal doxorubicin, paclitaxel and ifosfamide have activity but it is short-lived and not curative...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725232/transcriptome-wide-identification-of-differentially-expressed-genes-in-solanum-lycopersicon-l-in-response-to-an-alfalfa-protein-hydrolysate-using-microarrays
#15
Andrea Ertani, Michela Schiavon, Serenella Nardi
An alfalfa-based protein hydrolysate (EM) has been tested in tomato (Solanum lycopersicon L.) plants at two different concentrations (0.1 and 1 mL L(-1)) to get insight on its efficacy as biostimulant in this species and to unravel possible metabolic targets and molecular mechanisms that may shed light on its mode of action. EM was efficient in promoting the fresh biomass and content in chlorophyll and soluble sugars of tomato plants, especially when it was applied at the concentration of 1 mL L(-1). This effect on plant productivity was likely related to the EM-dependent up-regulation of genes identified via microarray and involved in primary carbon and nitrogen metabolism, photosynthesis, nutrient uptake and developmental processes...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28724693/new-peptide-inhibitor-of-dipeptidyl-peptidase-iv-emdb-1-extends-the-half-life-of-glp-2-and-attenuates-colitis-in-mice-after-topical-administration
#16
Maciej Salaga, Anna Mokrowiecka, Marta Zielinska, Ewa Malecka-Panas, Radzislaw Kordek, Elzbieta Kamysz, Jakub Fichna
Protease inhibition has become a new possible approach in the inflammatory bowel disease (IBD) therapy. A serine exopeptidase, dipeptidyl peptidase IV (DPP IV) is responsible for inactivation of incretine hormone, glucagon-like peptide 2 (GLP-2), a potent stimulator of intestinal epithelium regeneration and growth. Recently we showed that the novel peptide analog of endomorphin-2, EMDB-1 is a potent blocker of DPP IV and has an inhibitory effect on gastrointestinal (GI) smooth muscle contractility. The aim of this study was to characterize the anti-inflammatory effect and mechanism of action of EMDB-1 in the mouse GI tract...
July 19, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28724306/new-psychological-therapies-for-irritable-bowel-syndrome-mindfulness-acceptance-and-commitment-therapy-act
#17
Beatriz Sebastián Sánchez, Jesús Gil Roales-Nieto, Nuno Bravo Ferreira, Bárbara Gil Luciano, Juan José Sebastián Domingo
The current goal of treatment in irritable bowel syndrome (IBS) focuses primarily on symptom management and attempts to improve quality of life. Several treatments are at the disposal of physicians; lifestyle and dietary management, pharmacological treatments and psychological interventions are the most used and recommended. Psychological treatments have been proposed as viable alternatives or compliments to existing care models. Most forms of psychological therapies studied have been shown to be helpful in reducing symptoms and in improving the psychological component of anxiety/depression and health-related quality of life...
July 14, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28723893/in-vivo-crispr-screening-identifies-ptpn2-as-a-cancer-immunotherapy-target
#18
Robert T Manguso, Hans W Pope, Margaret D Zimmer, Flavian D Brown, Kathleen B Yates, Brian C Miller, Natalie B Collins, Kevin Bi, Martin W LaFleur, Vikram R Juneja, Sarah A Weiss, Jennifer Lo, David E Fisher, Diana Miao, Eliezer Van Allen, David E Root, Arlene H Sharpe, John G Doench, W Nicholas Haining
Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28722819/self-targeting-immune-transparent-plasma-protein-coated-nanocomplex-for-noninvasive-photothermal-anticancer-therapy
#19
Fwu-Long Mi, Thierry Burnouf, Shih-Yuan Lu, Yu-Jen Lu, Kun-Ying Lu, Yi-Cheng Ho, Chang-Yi Kuo, Er-Yuan Chuang
Cancer cells exhibit specific physiological differences compared to normal cells. Most surface membranes of cancer cells are characterized by high expression of given protein receptors, such as albumin, transferrin, and growth factors that are also present in the plasma of patients themselves, but are lacking on the surface of normal cells. These distinct features between cancer and normal cells can serve as a niche for developing specific treatment strategies. Near-infrared (NIR)-light-triggered therapy platforms are an interesting novel avenue for use in clinical nanomedicine...
July 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28722295/prevalence-correlates-and-impact-of-coronary-calcification-on-adverse-events-following-pci-with-newer-generation-des-findings-from-a-large-multiethnic-registry
#20
Robert S Copeland-Halperin, Usman Baber, Melissa Aquino, Anitha Rajamanickam, Swathi Roy, Choudhury Hasan, Nitin Barman, Jason C Kovacic, Pedro Moreno, Prakash Krishnan, Joseph M Sweeny, Roxana Mehran, George Dangas, Annapoorna S Kini, Samin K Sharma
OBJECTIVES: We sought to determine the prevalence, predictors, and clinical impact of target lesion calcification in patients undergoing percutaneous coronary intervention (PCI) with newer generation drug-eluting stents (DES) and devices. BACKGROUND: Coronary calcification is independently associated with adverse outcomes following PCI. While newer DES and contemporary devices are considered safer and more efficacious, their influence on outcomes following PCI of heavily calcified lesions is unknown...
July 19, 2017: Catheterization and Cardiovascular Interventions
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