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https://www.readbyqxmd.com/read/28092723/pertuzumab-and-breast-cancer-another-piece-in-the-anti-her2-puzzle
#1
Dr Lorenzo Gerratana, Dr Marta Bonotto, Dr Claudia Bozza, Dr Elena Ongaro, Dr Valentina Fanotto, Dr Giacomo Pelizzari, Prof Fabio Puglisi
The mechanism of action of pertuzumab, a recombinant anti-HER2 humanized monoclonal antibody, is complementary to trastuzumab's. On June 8, 2012, the Food and Drug Administration approved the combination of pertuzumab with trastuzumab and docetaxel as first-line treatment of HER2-positive metastatic breast cancer. Furthermore, pertuzumab is the first drug to be approved in the neoadjuvant setting using a pathological complete response as an endpoint. Areas covered: The review provides insights into the main mechanisms of action of pertuzumab...
January 16, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28092663/neural-regulation-of-immunity-molecular-mechanisms-and-clinical-translation
#2
REVIEW
Valentin A Pavlov, Kevin J Tracey
Studies bridging neuroscience and immunology have identified neural pathways that regulate immunity and inflammation. Recent research using methodological advances in molecular genetics has improved our understanding of the neural control of immunity. Here we outline mechanistic insights, focusing on translational relevance and conceptual developments. We also summarize findings from recent clinical studies of bioelectronic neuromodulation in inflammatory and autoimmune diseases.
January 16, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28092471/genomics-pipelines-and-data-integration-challenges-and-opportunities-in-the-research-setting
#3
Jeremy Davis-Turak, Sean M Courtney, E Starr Hazard, W Bailey Glen, Willian da Silveira, Timothy Wesselman, Larry P Harbin, Bethany J Wolf, Dongjun Chung, Gary Hardiman
The emergence and mass utilization of high-throughput (HT) technologies, including sequencing technologies (genomics) and mass spectrometry (proteomics, metabolomics, lipids), has allowed geneticists, biologists, and biostatisticians to bridge the gap between genotype and phenotype on a massive scale. These new technologies have brought rapid advances in our understanding of cell biology, evolutionary history, microbial environments, and are increasingly providing new insights and applications towards clinical care and personalized medicine...
January 16, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28092363/mouse-models-of-uv-induced-melanoma-genetics-pathology-and-clinical-relevance
#4
Chi-Ping Day, Rachel Marchalik, Glenn Merlino, Helen Michael
Melanocytes, a neural crest cell derivative, produce pigment to protect keratinocytes from ultraviolet radiation (UVR). Although melanocytic lesions such as nevi and cutaneous malignant melanomas are known to be associated with sun exposure, the role of UVR in oncogenesis is complex and has yet to be clearly elucidated. UVR appears to have a direct mutational role in inducing or promoting melanoma formation as well as an indirect role through microenvironmental changes. Recent advances in the modeling of human melanoma in animals have built platforms upon which prospective studies can begin to investigate these questions...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28092273/in-vivo-testing-of-extracorporeal-membrane-ventilators-ila-activve%C3%A2-vs-prototype-i-lung%C3%A2
#5
Sabine Kischkel, Stefan Bergt, Beate Brock, Johan von Grönheim, Anne Herbst, Marc-Jonas Epping, Georg Matheis, Esther Novosel, Joerg Schneider, Philipp Warnke, Andreas Podbielski, Jan P Roesner, Peter I Lelkes, Brigitte Vollmar
A side-by-side comparison of the decarboxylation efficacy of two pump-driven veno-venous extracorporeal lung assist devices, i.e. a first prototype of the new miniaturized ambulatory extracorporeal membrane ventilator, I-lung® versus the commercial system iLA-activve® over a period of 72 hours in a large animal model.Fifteen German Landrace pigs were anesthetized and underwent mechanical hypoventilation to induce severe hypercapnia. Decarboxylation was accomplished by either the I-lung® or the iLA-activve® via a double lumen catheter in the jugular vein...
January 4, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/28090649/-the-pharmacogenomics-research-network-translational-pharmacogenetics-program-outcomes-and-metrics-of-pharmacogenetic-implementations-across-diverse-healthcare-systems
#6
Jasmine A Luzum, Ruth E Pakyz, Amanda R Elsey, Cyrine E Haidar, Josh F Peterson, Michelle Whirl-Carrillo, Samuel K Handelman, Kathleen Palmer, Jill M Pulley, Marc Beller, Jonathan S Schildcrout, Julie R Field, Kristin W Weitzel, Rhonda M Cooper-DeHoff, Larisa H Cavallari, Peter H O'Donnell, Russ B Altman, Naveen Pereira, Mark J Ratain, Dan M Roden, Peter J Embi, Wolfgang Sadee, Teri E Klein, Julie A Johnson, Mary V Relling, Liewei Wang, Richard M Weinshilboum, Alan R Shuldiner, Robert R Freimuth
Numerous pharmacogenetic clinical guidelines and recommendations have been published, but barriers have hindered the clinical implementation of pharmacogenetics. The Translational Pharmacogenetics Program (TPP) of the NIH Pharmacogenomics Research Network was established in 2011 to catalog and contribute to the development of pharmacogenetic implementations at eight US healthcare systems, with the goal to disseminate real-world solutions for the barriers to clinical pharmacogenetic implementation. The TPP collected and normalized pharmacogenetic implementation metrics through June 2015, including gene-drug pairs implemented, interpretations of alleles and diplotypes, numbers of tests performed and actionable results, and workflow diagrams...
January 16, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28090637/diltiazem-prevents-stress-induced-contractile-deficits-in-cardiomyocytes-but-does-not-reverse-the-cardiomyopathy-phenotype-in-mybpc3-knock-in-mice
#7
Frederik Flenner, Birgit Geertz, Silke Reischmann-Düsener, Florian Weinberger, Thomas Eschenhagen, Lucie Carrier, Felix W Friedrich
Left ventricular hypertrophy, diastolic dysfunction and fibrosis are main features of hypertrophic cardiomyopathy (HCM). Guidelines recommend β-adrenoceptor or Ca(2+) channel antagonists as pharmacological treatment. The Ca(2+) channel blocker diltiazem recently showed promising beneficial effects in pre-clinical HCM, particularly in patients carrying MYBPC3 mutations. In the present study we evaluated whether diltiazem could ameliorate or reverse the disease phenotype in cells and in vivo in Mybpc3-targeted knock-in (KI) mouse model of HCM...
January 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28090599/mas-related-g-protein-coupled-receptor-x2-a-potential-new-target-for-modulating-mast-cell-mediated-allergic-and-inflammatory-diseases
#8
Hydar Ali
Mast cells (MCs) are tissue resident immune cells that are best known for their roles in allergic and inflammatory diseases. In addition to the high affinity IgE receptor (FcεRI), MCs express numerous G protein coupled receptors (GPCRs), which are the most common targets of drug therapy. Neurokinin 1 receptor (NK-1R) is expressed on MCs and contributes to IgE and non-IgE-mediated responses in mice. Although NK-1R antagonists are highly effective in modulating experimental allergic and inflammatory responses in mice they lack efficacy in humans...
December 2016: Journal of Immunobiology
https://www.readbyqxmd.com/read/28090566/large-animal-models-the-key-to-translational-discovery-in-digestive-disease-research
#9
Amanda Ziegler, Liara Gonzalez, Anthony Blikslager
Gastrointestinal disease is a prevalent cause of morbidity and mortality and the use of animal models have been instrumental in studying mechanisms of digestive pathophysiology. As investigators attempt to translate the wealth of basic science information developed from rodent, models, large animal models provide a number of translational advantages. The pig, in particular, is arguably one of the most powerful models of human organ systems, including the gastrointestinal tract. The pig has provided important tools and insight into intestinal ischemia/reperfusion injury, intestinal mucosal repair, as well as new insights into esophageal injury and repair...
November 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28090514/pancreatic-cancer-from-bench-to-bedside
#10
REVIEW
Yaokai Ma, Qing Wu, Xin Li, Xiaoqiang Gu, Jiahua Xu, Jinzu Yang
Pancreatic cancer is recognized as the king of carcinoma, and the gap between basic research and clinical practice is difficult to improve the treatment effect. Translational medicine builds an important bridge between pancreatic cancer basic research and clinical practice from the pathogenesis, early diagnosis of pancreatic carcinoma, drug screening, treatment strategies and metastasis prediction. This article will carry on the concrete elaboration to the above several aspects.
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28090374/neurophysiological-measures-and-alcohol-use-disorder-aud-hypothesizing-links-between-clinical-severity-index-and-molecular-neurobiological-patterns
#11
Mario Vitali, Carmen Napolitano, Marlene Oscar Berman, Simona Flamminii Minuto, Gemma Battagliese, Maria Luisa Attilia, Eric R Braverman, Marina Romeo, Kenneth Blum, Mauro Ceccanti
BACKGROUND: In 1987, Cloninger proposed a clinical description and classification of different personality traits genetically defined and independent from each other. Moreover, he elaborated a specific test the TCI to investigate these traits/states. The study of craving in Alcohol Use Disorder (AUD) assumed a greater significance, since ever more data seems to suggest a direct correlation between high levels of craving and a higher risk of relapse in alcoholics. Thus, our study aim is to explore the possible correlations among TCI linked molecular neurobiological pattern (s), craving and alcohol addiction severity measures in a sample of Italian alcoholics...
April 2016: Journal of Addiction Research & Therapy
https://www.readbyqxmd.com/read/28089669/exposure-to-gdnf-enhances-the-ability-of-enteric-neural-progenitors-to%C3%A2-generate-an-enteric-nervous-system
#12
Sonja J McKeown, Mitra Mohsenipour, Annette J Bergner, Heather M Young, Lincon A Stamp
Cell therapy is a promising approach to generate an enteric nervous system (ENS) and treat enteric neuropathies. However, for translation to the clinic, it is highly likely that enteric neural progenitors will require manipulation prior to transplantation to enhance their ability to migrate and generate an ENS. In this study, we examine the effects of exposure to several factors on the ability of ENS progenitors, grown as enteric neurospheres, to migrate and generate an ENS. Exposure to glial-cell-line-derived neurotrophic factor (GDNF) resulted in a 14-fold increase in neurosphere volume and a 12-fold increase in cell number...
January 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28089559/microglia-derived-neuregulin-expression-in-psychiatric-disorders
#13
Daisuke Ikawa, Manabu Makinodan, Keiko Iwata, Masahiro Ohgidani, Takahiro A Kato, Yasunori Yamashita, Kazuhiko Yamamuro, Sohei Kimoto, Michihiro Toritsuka, Takahira Yamauchi, Shin-Ichi Fukami, Hiroki Yoshino, Kazuki Okumura, Tatsuhide Tanaka, Akio Wanaka, Yuji Owada, Masatsugu Tsujii, Toshiro Sugiyama, Kenji Tsuchiya, Norio Mori, Ryota Hashimoto, Hideo Matsuzaki, Shigenobu Kanba, Toshifumi Kishimoto
Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorders (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD...
January 9, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28089498/anticoagulants-in-ischemia-guided-management-of-non-st-elevation-acute-coronary-syndromes
#14
REVIEW
Martin Mayer
BACKGROUND: The most recent joint guidelines from the American Heart Association (AHA) and American College of Cardiology (ACC) on the management of non-ST-elevation acute coronary syndromes (NSTE-ACS) are a result of a substantial and considered undertaking, and those involved deserve much recognition for their efforts. However, the handling of anticoagulants seems somewhat inadequate, and this is a highly-relevant matter when managing NSTE-ACS. OBJECTIVE OF THE REVIEW: Among areas of potential uncertainty, emergency medicine professionals might still be left wondering about the particulars of anticoagulant therapy when pursuing ischemia-guided management of NSTE-ACS (that is, managing NSTE-ACS without an intent for early invasive measures, such as coronary angiography and revascularization)...
January 3, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28089422/low-magnitude-mechanical-signals-and-the-spine-a-review-of-current-and-future-applications
#15
REVIEW
Martin H Pham, Zorica Buser, Jeffrey C Wang, Frank L Acosta
Animal and human studies demonstrate the anabolic properties of low-magnitude mechanical stimulation (LMMS) in its ability to improve bone formation by enhancing the proliferation of mesenchymal stem cells and their subsequent commitment down an osteoblastic lineage. Response to mechanical strains as low as 10μɛ have been seen, illustrating the sensitivity of mechanosensory cells to mechanotransduction pathways. Applications to the spine include treatment of osteoporosis in preparation for instrumented fusion, fracture reduction in spinal cord injury patients to slow bone mineral density loss, and bone tissue engineering and enhancement of bone-implant osseointegration for pseudarthrosis and hardware failure...
January 12, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28089350/rickettsia-prowazekii-methionine-aminopeptidase-as-a-promising-target-for-the-development-of-antibacterial-agents
#16
Travis R Helgren, Congling Chen, Phumvadee Wangtrakuldee, Thomas E Edwards, Bart L Staker, Jan Abendroth, Banumathi Sankaran, Nicole A Housley, Peter J Myler, Jonathon P Audia, James R Horn, Timothy J Hagen
Methionine aminopeptidase (MetAP) is a class of ubiquitous enzymes essential for the survival of numerous bacterial species. These enzymes are responsible for the cleavage of N-terminal formyl-methionine initiators from nascent proteins to initiate post-translational modifications that are often essential to proper protein function. Thus, inhibition of MetAP activity has been implicated as a novel antibacterial target. We tested this idea in the present study by targeting the MetAP enzyme in the obligate intracellular pathogen Rickettsia prowazekii...
November 10, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28089339/discovery-of-a-murine-model-of-clinical-pah-mission-impossible
#17
REVIEW
Zhiyu Dai, You-Yang Zhao
Pulmonary arterial hypertension (PAH) is a lung vascular disease characterized with a progressive increase of pulmonary vascular resistance and obliterative pulmonary vascular remodeling resulting in right heart failure and premature death. In this brief review, we document the recent advances in identifying genetically modified murine models of PH, with a focus on the recent discovery of the mouse model of Tie2 Cre-mediated deletion of prolyl hydroxylase 2, which exhibits progressive obliterative vascular remodeling, severe PAH, and right heart failure, thus recapitulating many of the features of clinical PAH...
December 15, 2016: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28089230/metastatic-fractures-of-long-limb-bones
#18
REVIEW
P Anract, D Biau, P Boudou-Rouquette
The diagnosis of pathological fracture should be considered routinely in patients with long limb-bone fractures. Investigations must be performed to establish the diagnosis of pathological fracture then to determine that the bone lesion is a metastasis. In over 85% of cases, the clinical evaluation combined with a detailed analysis of the radiographs is sufficient to determine that the fracture occurred at a tumour site. Aetiological investigations establish that the tumour is a metastasis. In some patients, the diagnosis of metastatic cancer antedates the fracture...
January 11, 2017: Orthopaedics & Traumatology, Surgery & Research: OTSR
https://www.readbyqxmd.com/read/28088893/intervention-for-cardiac-repair-a-clinical-perspective
#19
Hui Na Tan, Zhe Yuan Tay, Boon Seng Soh
Cardiovascular disease remains the leading cause of death worldwide. Damage to the heart resulting from cardiovascular disease leads to gradual loss of function and reduced quality of life. Cardiac injury is particularly debilitating, more so than injury to any other organ given our current inability to either generate new and functional cardiac tissue or to mimic the actions of the heart using external devices. Advances in the field of stem cells and genetics have paved the way for the development of a variety of novel therapies...
January 12, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28088839/pharmacokinetic-pharmacodynamic-modeling-of-the-pde4-inhibitor-tak-648-in-type-2-diabetes-early-translational-approaches-for-human-dose-prediction
#20
N Plock, S Vollert, M Mayer, G Hanauer, G Lahu
TAK-648 is a PDE4 inhibitor with demonstrated preclinical antidiabetic properties. Our objective was to develop a translational pharmacokinetic/pharmacodynamic (PK/PD) model for human type 2 diabetes (T2D) dose prediction using HbA1c results from a db/db mouse study. Estimated parameters in combination with tPDE4i values calculated for the clinical roflumilast dose of 500 μg were used to translate preclinical effects of TAK-648 to required exposure in humans. A first-in-human study with single TAK-648 doses of 0...
January 15, 2017: Clinical and Translational Science
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