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https://www.readbyqxmd.com/read/28213714/-current-biomarkers-for-gastric-cancer
#1
G B Baretton, D E Aust
Gastric cancer is still a relevant malignant disease with high morbidity and mortality. Current molecular genetic data show that gastric cancer, as other solid tumors as well, is not a single entity but consists of several molecular subtypes of gastric cancer with diverse biology. The increasing understanding of molecular pathways is the basis for innovative therapies. These either directly target altered signaling pathways or genes in tumor cells or as in immune checkpoint inhibitors, indirectly target tumor cells by blocking tumor-induced immune inhibition leading to improvement in the prognosis...
February 17, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#2
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28211993/recent-lab-on-chip-developments-for-novel-drug-discovery
#3
REVIEW
Nauman Khalid, Isao Kobayashi, Mitsutoshi Nakajima
Microelectromechanical systems (MEMS) and micro total analysis systems (μTAS) revolutionized the biochemical and electronic industries, and this miniaturization process became a key driver for many markets. Now, it is a driving force for innovations in life sciences, diagnostics, analytical sciences, and chemistry, which are called 'lab-on-a-chip, (LOC)' devices. The use of these devices allows the development of fast, portable, and easy-to-use systems with a high level of functional integration for applications such as point-of-care diagnostics, forensics, the analysis of biomolecules, environmental or food analysis, and drug development...
February 17, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28211784/generic-antiretrovirals-for-the-treatment-of-hiv-a-novel-challenge-for-western-countries-%C3%A2
#4
Dario Cattaneo, Massimo Andreoni, Gianpiero Carosi, Roberto Cauda, Adriano Lazzarin, Giuliano Rizzardini
The introduction of generic antiretroviral medications in developing countries has resulted in significant CD4 cell restoration, HIV viral decline, and a noteworthy reduction in the time to initiation of therapy. Projection models have also predicted significant cost saving associated with the extensive diffusion of generic antiretrovirals in developed countries. However, some uncertainties on generics have recently been raised. These concerns mainly relate to the adequacy of the study design for bioequivalence testing, the potential for uncontrolled switching from one generic to another, and the loss of adherence if patients switched from fixed-dose coformulations to single components in order to incorporate the new generic drugs...
February 17, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28211195/a-comparison-of-the-new-japanese-expedited-approval-legislation-for-regenerative-medicine-product-with-the-existing-systems-of-the-united-states-and-european-union
#5
Yoji Jokura, Kazuo Yano, Masayuki Yamato
Expedited approval pathways/programs for drugs, biologics, or medical devices have been enacted for rapid product commercialization of innovative products in the United States (US) and European Union (EU). However, less innovative products are increasingly using these expedited pathways and frequently obligations to collect and report post-marketing data on approved products are being bypassed. The Japanese government recently enacted a new conditional and time-limited approval pathway dedicated to regenerative medicine products...
February 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28206814/biomarkers-in-tumor-microenvironment-upregulation-of-fibroblast-activation-protein-%C3%AE-correlates-with-gastric-cancer-progression-and-poor-prognosis
#6
Mengmou Hu, Chengjia Qian, Ziwei Hu, Bojian Fei, Haibo Zhou
Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recent evidence points to importance of cross talk between cancer cells and the surrounding stroma on gastric cancer progression. Tumor microenvironment biomarkers thus represent a new opportunity for diagnostics innovation. Reactive stromal fibroblasts selectively express the fibroblast activation protein alpha (FAP-α), a homodimeric integral membrane gelatinase that belongs to the serine protease family. We report here that FAP-α expression is significantly elevated in gastric cancer samples by more than fivefold (p < 0...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28205621/cryogel-supported-stem-cell-factory-for-customized-sustained-release-of-bispecific-antibodies-for-cancer-immunotherapy
#7
Roberta Aliperta, Petra B Welzel, Ralf Bergmann, Uwe Freudenberg, Nicole Berndt, Anja Feldmann, Claudia Arndt, Stefanie Koristka, Marcello Stanzione, Marc Cartellieri, Armin Ehninger, Gerhard Ehninger, Carsten Werner, Jens Pietzsch, Jörg Steinbach, Martin Bornhäuser, Michael P Bachmann
Combining stem cells with biomaterial scaffolds provides a promising strategy for the development of drug delivery systems. Here we propose an innovative immunotherapeutic organoid by housing human mesenchymal stromal cells (MSCs), gene-modified for the secretion of an anti-CD33-anti-CD3 bispecific antibody (bsAb), in a small biocompatible star-shaped poly(ethylene glycol)-heparin cryogel scaffold as a transplantable and low invasive therapeutic machinery for the treatment of acute myeloid leukemia (AML). The macroporous biohybrid cryogel platform displays effectiveness in supporting proliferation and survival of bsAb-releasing-MSCs overtime in vitro and in vivo, avoiding cell loss and ensuring a constant release of sustained and detectable levels of bsAb capable of triggering T-cell-mediated anti-tumor responses and a rapid regression of CD33(+) AML blasts...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203341/new-monoclonal-antibodies-on-the-horizon-in-multiple-myeloma
#8
REVIEW
Elizabeth K O'Donnell, Noopur S Raje
Across all cancers, monoclonal antibodies have emerged as a potential strategy for cancer therapy. Monoclonal antibodies target antigens expressed on the surface of cancer cells and accessory cells. This targeted approach uses the host's immune system to promote the killing of cancer cells. Multiple myeloma (MM) is the second most common hematologic malignancy that remains incurable in the majority of patients. The treatment of MM has evolved dramatically over the past decade and continues to evolve with the approval of four new drugs in 2015...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28199324/establishing-a-reliable-framework-for-harnessing-the-creative-power-of-the-scientific-crowd
#9
Adrian J Carter, Amy Donner, Wen Hwa Lee, Chas Bountra
Discovering new medicines is difficult and increasingly expensive. The pharmaceutical industry has responded to this challenge by embracing open innovation to access external ideas. Historically, partnerships were usually bilateral, and the drug discovery process was shrouded in secrecy. This model is rapidly changing. With the advent of the Internet, drug discovery has become more decentralised, bottom-up, and scalable than ever before. The term open innovation is now accepted as just one of many terms that capture different but overlapping levels of openness in the drug discovery process...
February 2017: PLoS Biology
https://www.readbyqxmd.com/read/28198177/innovative-molecular-targeted-agents-in-hepatocellular-carcinoma-new-gladiators-on-the-arena
#10
Jose Ferri, Yanina Dockx, Luisa Vonghia, Konstantinos Papadimitriou, Marika Rasschaert, Sven Francque, Marc Peeters, Christian Rolfo
Treatment of advanced hepatocellular carcinoma remains a challenge, with discouraging results in terms of survival. Following the approval of the multikinase inhibitor sorafenib, a large number of molecular targeted agents have been tested, but many have failed to demonstrate significant efficacy in clinical trials. However, the deeper knowledge in HCC pathogenesis achieved through the years has enabled us to explore new targetable pathways as well as biomarkers that could lead to treatment personalization...
February 14, 2017: Minerva Chirurgica
https://www.readbyqxmd.com/read/28196272/deep-sequencing-of-71-candidate-genes-to-characterize-variation-associated-with-alcohol-dependence
#11
Shaunna L Clark, Daniel E Adkins, Gaurav Kumar, Karolina A Aberg, Sri Nerella, Linying Xie, Ann L Collins, James J Crowley, Corey R Quackenbush, Christopher E Hilliard, Andrey A Shabalin, Scott I Vrieze, Roseann E Peterson, William E Copeland, Judy L Silberg, Matt McGue, Hermine Maes, William G Iacono, Patrick F Sullivan, Elizabeth J Costello, Edwin J van den Oord
BACKGROUND: Previous genome-wide association studies (GWASs) have identified a number of putative risk loci for alcohol dependence (AD). However, only a few loci have replicated and these replicated variants only explain a small proportion of AD risk. Using an innovative approach, the goal of this study was to generate hypotheses about potentially causal variants for AD that can be explored further through functional studies. METHODS: We employed targeted capture of 71 candidate loci and flanking regions followed by next-generation deep sequencing (mean coverage 78X) in 806 European Americans...
February 14, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28195732/in-vivo-predictive-dissolution-ipd-and-biopharmaceutical-modeling-and-simulation-future-use-of-modern-approaches-and-methodologies-in-a-regulatory-context
#12
H Lennernas, A Lindahl, A Van Peer, C Ollier, T Flanagan, R Lionberger, A Nordmark, S Yamashita, L Yu, G L Amidon, V Fischer, E Sjögren, P Zane, M McAllister, B Abrahamsson
The overall objective of OrBiTo, a project within Innovative Medicines Initiative (IMI), is to streamline and optimize the development of orally administered drug products through the creation and efficient application of biopharmaceutics tools. This toolkit will include both experimental and computational models developed on improved understanding of the highly dynamic gastrointestinal (GI) physiology relevant to the GI absorption of drug products in both fasted and fed states. A part of the annual OrBiTo-meeting in 2015 was dedicated to the presentation of the most recent progress in the development of the regulatory use of PBPK in silico modeling, in vivo predictive dissolution (IPD) tests and their application to biowaivers...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28195238/the-changing-landscape-of-clinical-trial-and-approval-processes-in-china
#13
REVIEW
Qing Zhou, Xiao-Yuan Chen, Zhi-Min Yang, Yi-Long Wu
In the past decade, the standards of clinical trials in China have moved closer to international standards, thus encouraging the development of innovative drugs. However, a large backlog of pending applications for both drug approval and clinical trial registration has arisen owing to the complexity of the approval process, the volume of applications and a lack of staff available to process these applications, among other reasons. To improve the drug approval process, a 'four-colour-light' strategy was introduced...
February 14, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28194770/clinical-pharmacology-therapeutics-past-present-and-future
#14
EDITORIAL
S A Waldman, A Terzic
Clinical Pharmacology & Therapeutics (CPT), the definitive and timely source for advances in human therapeutics, transcends the drug discovery, development, regulation, and utilization continuum to catalyze, evolve, and disseminate discipline-transformative knowledge. Prioritized themes and multidisciplinary content drive the science and practice of clinical pharmacology, offering a trusted point of reference. An authoritative herald across global communities, CPT is a timeless information vehicle at the vanguard of discovery, translation, and application ushering therapeutic innovation into modern healthcare...
March 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28194329/understanding-breast-cancer-the-long-and-winding-road
#15
REVIEW
Kiven Erique Lukong
BACKGROUND: Despite a remarkable increase in the depth of our understanding and management of breast cancer in the past 50 years, the disease is still a major public health problem worldwide and poses significant challenges. The palpability of breast tumors has facilitated diagnosis and documentation since ancient times. The earliest descriptions of breast cancer date back to around 3500 BCE. For centuries to follow, theories by Hippocrates (460 BCE) and Galen (200 CE), attributing the cause of breast cancer to an "excess of black bile" and treatment options including the use of opium and castor oil, prevailed...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28193768/exploiting-the-p53-pathway-for-therapy
#16
Chit Fang Cheok, David Philip Lane
The excitement around the entry into the clinic of the first generation of p53-specific drugs has become muted as the hoped-for dramatic clinical responses have not yet been seen. However, these pioneer molecules have become exceptionally powerful tools in the analysis of the p53 pathway and, as a result, a whole spectrum of new interventions are being explored. These include entirely novel and innovative approaches to drug discovery, such as the use of exon-skipping antisense oligonucleotides and T-cell-receptor-based molecules...
February 13, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28193222/phosphorylation-dependent-regulation-of-aldh1a1-by-aurora-kinase-a-insights-on-their-synergistic-relationship-in-pancreatic-cancer
#17
Jing Wang, Kumar Nikhil, Keith Viccaro, Lei Chang, Jacoba White, Kavita Shah
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) formation are key underlying causes that promote extensive metastasis, drug resistance, and tumor recurrence in highly lethal pancreatic cancer. The mechanisms leading to EMT and CSC phenotypes are not fully understood, which has hindered the development of effective targeted therapies capable of improving treatment outcomes in patients with pancreatic cancer. RESULTS: We show a central role of Aurora kinase A (AURKA) in promoting EMT and CSC phenotypes via ALDH1A1, which was discovered as its direct substrate using an innovative chemical genetic screen...
February 13, 2017: BMC Biology
https://www.readbyqxmd.com/read/28192916/combating-enhanced-intracellular-survival-eis-mediated-kanamycin-resistance-of-mycobacterium-tuberculosis-by-novel-pyrrolo-1-5-a-pyrazine-based-eis-inhibitors
#18
Atefeh Garzan, Melisa J Willby, Huy X Ngo, Chathurada S Gajadeera, Keith D Green, Selina Y L Holbrook, Caixia Hou, James E Posey, Oleg V Tsodikov, Sylvie Garneau-Tsodikova
Tuberculosis (TB) remains one of the leading causes of mortality worldwide. Hence, the identification of highly effective antitubercular drugs with novel modes of action is crucial. In this paper, we report the discovery and development of pyrrolo[1,5-a]pyrazine-based analogues as highly potent inhibitors of the Mycobacterium tuberculosis (Mtb) acetyltransferase enhanced intracellular survival (Eis), whose up-regulation causes clinically observed resistance to the aminoglycoside (AG) antibiotic kanamycin A (KAN)...
February 17, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28192425/improving-access-to-chagas-disease-diagnosis-and-etiologic-treatment-in-remote-rural-communities-of-the-argentine-chaco-through-strengthened-primary-health-care-and-broad-social-participation
#19
Paula Sartor, Ivana Colaianni, M Victoria Cardinal, Jacqueline Bua, Héctor Freilij, Ricardo E Gürtler
BACKGROUND: Rural populations in the Gran Chaco region have large prevalence rates of Trypanosoma cruzi infection and very limited access to diagnosis and treatment. We implemented an innovative strategy to bridge these gaps in 13 rural villages of Pampa del Indio held under sustained vector surveillance and control. METHODOLOGY: The non-randomized treatment program included participatory workshops, capacity strengthening of local health personnel, serodiagnosis, qualitative and quantitative PCRs, a 60-day treatment course with benznidazole and follow-up...
February 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28192094/filovirus-proteins-for-antiviral-drug-discovery-structure-function-bases-of-the-replication-cycle
#20
REVIEW
Baptiste Martin, Bruno Canard, Etienne Decroly
Filoviruses are important pathogens that cause severe and often fatal hemorrhagic fever in humans, for which no approved vaccines and antiviral treatments are yet available. In an earlier article (Martin et al., Antiviral Research, 2016), we reviewed the role of the filovirus surface glycoprotein in replication and as a target for drugs and vaccines. In this review, we focus on recent findings on the filovirus replication machinery and how they could be used for the identification of new therapeutic targets and the development of new antiviral compounds...
February 9, 2017: Antiviral Research
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