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Preclinical models

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https://www.readbyqxmd.com/read/28535507/cardiac-cell-therapies-for-the-treatment-of-acute-myocardial-infarction-a-meta-analysis-from-mouse-studies
#1
Cajetan Immanuel Lang, Markus Wolfien, Anne Langenbach, Paula Müller, Olaf Wolkenhauer, Arash Yavari, Hüseyin Ince, Gustav Steinhoff, Bernd Joachim Krause, Robert David, Änne Glass
AIMS: Stem cell-based regenerative therapies for the treatment of ischemic myocardium are currently a subject of intensive investigation. A variety of cell populations have been demonstrated to be safe and to exert some positive effects in human Phase I and II clinical trials, however conclusive evidence of efficacy is still lacking. While the relevance of animal models for appropriate pre-clinical safety and efficacy testing with regard to application in Phase III studies continues to increase, concerns have been expressed regarding the validity of the mouse model to predict clinical results...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28535157/a-meta-analysis-of-cxcl12-expression-for-cancer-prognosis
#2
Harsh Samarendra, Keaton Jones, Tatjana Petrinic, Michael A Silva, Srikanth Reddy, Zahir Soonawalla, Alex Gordon-Weeks
BACKGROUND: CXCL12 (SDF1) is reported to promote cancer progression in several preclinical models and this is corroborated by the analysis of human tissue specimens. However, the relationship between CXCL12 expression and cancer survival has not been systematically assessed. METHODS: We conducted a systematic review and meta-analysis of studies that evaluated the association between CXCL12 expression and cancer survival. RESULTS: Thirty-eight studies inclusive of 5807 patients were included in the analysis of overall, recurrence-free or cancer-specific survival, the majority of which were retrospective...
May 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28534796/predicting-progression-from-mild-cognitive-impairment-to-alzheimer-s-disease-using-autoregressive-modelling-of-longitudinal-and-multimodal-biomarkers
#3
Sidra Minhas, Aasia Khanum, Farhan Riaz, Shoab Khan, Atif Alvi
Mild Cognitive Impairment is a preclinical stage of Alzheimer's disease (AD). For effective treatment of AD, it is important to identify MCI patients who are at a high risk of developing AD over the course of time. İn this study, autoregressive modelling of multiple heterogeneous predictors of Alzheimer's dısease is performed to capture their evolution over time. The models are trained using three different arrangements of longitudinal data. These models are then used to estimate future biomarker readings of individual test subjects...
May 16, 2017: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/28534535/the-potential-of-organoids-in-urological-cancer-research
#4
REVIEW
Shangqian Wang, Dong Gao, Yu Chen
Technical advances in the development of organoid systems enable cell lines, primary adult cells, or stem or progenitor cells to develop into diverse, multicellular entities, which can self-renew, self-organize, and differentiate. These 3D organoid cultures have proven to be of value in increasing our understanding of the biology of disease and offer the potential of regenerative and genetic therapies. The successful application of 3D organoids derived from adult tissue into urological cancer research can further our understanding of these diseases and could also provide preclinical cancer models to realize the precision medicine paradigm by therapeutic screening of individual patient samples ex vivo...
May 23, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28534531/unravelling-the-biology-of-sclc-implications-for-therapy
#5
REVIEW
Joshua K Sabari, Benjamin H Lok, James H Laird, John T Poirier, Charles M Rudin
Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints...
May 23, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28534338/-application-and-development-of-patient-derived-tumor-xenograft-model-in-translational-medicine-of-tumor
#6
Zhenqiang Wang, Zhenggang Zhu
Development of novel drugs is an integral part of the translational medicine in the field of cancer research, and the construction and application of preclinical animal models play vital roles in drugs development. Patient-derived tumor xenograft models (PDX) have been shown to be more accurate in prediction of clinical outcomes of novel drugs and are being used for preclinical drug evaluation based on the fact that PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor...
May 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28533484/insights-from-animal-models-of-bladder-cancer-recent-advances-challenges-and-opportunities
#7
REVIEW
Bincy Anu John, Neveen Said
Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with increasing incidence and mortality. Treatment of bladder cancer has not advanced in the past 30 years. Therefore, there is a crucial unmet need for novel therapies, especially for high grade/stage disease that can only be achieved by preclinical model systems that faithfully recapitulate the human disease. Animal models are essential elements in bladder cancer research to comprehensively study the multistep cascades of carcinogenesis, progression and metastasis...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533414/manipulating-dna-damage-response-signaling-for-the-treatment-of-immune-mediated-diseases
#8
Jonathan P McNally, Scott H Millen, Vandana Chaturvedi, Nora Lakes, Catherine E Terrell, Eileen E Elfers, Kaitlin R Carroll, Simon P Hogan, Paul R Andreassen, Julie Kanter, Carl E Allen, Michael M Henry, Jay N Greenberg, Stephan Ladisch, Michelle L Hermiston, Michael Joyce, David A Hildeman, Jonathan D Katz, Michael B Jordan
Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response (DDR) signaling pathways would allow for selective therapeutic targeting of pathological T cells in disease contexts. Consistent with these hypotheses, we found that activated mouse and human T cells display a pronounced DDR in vitro and in vivo...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533295/comparative-pathogenesis-of-autoimmune-diabetes-in-humans-nod-mice-and-canines-has-a-valuable-animal-model-of-type-1-diabetes-been-overlooked
#9
Allison L O'Kell, Clive Wasserfall, Brian Catchpole, Lucy J Davison, Rebecka S Hess, Jake A Kushner, Mark A Atkinson
Despite decades of research in humans and mouse models of disease, substantial gaps remain in our understanding of pathogenic mechanisms underlying the development of type 1 diabetes. Furthermore, translation of therapies from preclinical efforts capable of delaying or halting β-cell destruction has been limited. Hence, a pressing need exists to identify alternative animal models that reflect human disease. Canine insulin deficiency diabetes is, in some cases, considered to follow autoimmune pathogenesis, similar to NOD mice and humans, characterized by hyperglycemia requiring lifelong exogenous insulin therapy...
June 2017: Diabetes
https://www.readbyqxmd.com/read/28532501/pik3ca-hotspot-mutations-differentially-impact-responses-to-met-targeting-in-met-driven-and-non-driven-preclinical-cancer-models
#10
Lluís Nisa, Pascal Häfliger, Michaela Poliaková, Roland Giger, Paola Francica, Daniel Matthias Aebersold, Roch-Philippe Charles, Yitzhak Zimmer, Michaela Medová
BACKGROUND: The MET receptor tyrosine kinase represents a promising target in cancer. PIK3CA activating mutations are common in several tumor types and can potentially confer resistance to anti-receptor tyrosine kinase therapy. METHODS: MET and/or PI3K pathway inhibition was assessed in NIH3T3 cells harboring MET-activating point mutation with or without ectopic expression of PIK3CA(E545K) and PIK3CA(H1047R), as well as in MET-expressing head and neck cancer cells with endogenous PIK3CA mutations...
May 22, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28531297/mechanisms-of-kappa-opioid-receptor-potentiation-of-dopamine-d2-receptor-function-in-quinpirole-induced-locomotor-sensitization-in-rats
#11
Angélica P Escobar, Marcela P González, Rodrigo C Meza, Verónica Noches, Pablo Henny, Katia Gysling, Rodrigo A España, José A Fuentealba, María E Andrés
Background: Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of Quinpirole (QNP), a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist (KOR). The mechanism underlying KOR potentiation of QNP-induced locomotor sensitization remains to be elucidated...
May 22, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28531256/advances-in-preclinical-models-of-frailty
#12
Alice E Kane, Susan E Howlett
No abstract text is available yet for this article.
May 20, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28530834/a-facile-radiolabeling-of-18-f-fdpa-via-spirocyclic-iodonium-ylides-preliminary-pet-imaging-studies-in-preclinical-models-of-neuroinflammation
#13
Lu Wang, Ran Cheng, Masayuki Fujinaga, Jian Yang, Yiding Zhang, Akiko Hatori, Katsushi Kumata, Jing Yang, Neil Vasdev, Yunfei Du, Chongzhao Ran, Ming-Rong Zhang, Steven H Liang
A suitable TSPO PET ligand may visualize and quantify neuroinflammation in living brain. Herein we report a (18)F-ligand, [(18)F]2 ([(18)F]FDPA) is radiolabeled in high yield and high specific activity based on our spirocyclic iodonium ylide (SCIDY) strategy. [(18)F]2 demonstrated saturable specific binding to TSPO, substantially-elevated brain uptake and slow washout of bound PET signal in the preclinical models of brain neuroinflammation (cerebral ischemia and Alzheimer's disease).
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28529633/noninvasive-assessment-of-elimination-and-retention-using-ct-fmt-and-kinetic-whole-body-modeling
#14
Wa'el Al Rawashdeh, Simin Zuo, Andrea Melle, Lia Appold, Susanne Koletnik, Yoanna Tsvetkova, Nataliia Beztsinna, Andrij Pich, Twan Lammers, Fabian Kiessling, Felix Gremse
Fluorescence-mediated tomography (FMT) is a quantitative three-dimensional imaging technique for preclinical research applications. The combination with micro-computed tomography (µCT) enables improved reconstruction and analysis. The aim of this study is to assess the potential of µCT-FMT and kinetic modeling to determine elimination and retention of typical model drugs and drug delivery systems. We selected four fluorescent probes with different but well-known biodistribution and elimination routes: Indocyanine green (ICG), hydroxyapatite-binding OsteoSense (OS), biodegradable nanogels (NG) and microbubbles (MB)...
2017: Theranostics
https://www.readbyqxmd.com/read/28529486/the-role-of-statins-in-prevention-of-preeclampsia-a-promise-for-the-future
#15
REVIEW
Vasiliki Katsi, Georgios Georgountzos, Manolis S Kallistratos, Ioannis Zerdes, Thomas Makris, Athanasios J Manolis, Petros Nihoyannopoulos, Dimitris Tousoulis
Preeclampsia has been linked to high morbidity and mortality during pregnancy. However, no efficient pharmacological options for the prevention of this condition are currently available. Preeclampsia is thought to share several pathophysiologic mechanisms with cardiovascular disease, which has led to investigations for the potential role of statins (HMG CoA reductase inhibitors) in its prevention and early management. Pravastatin seems to have a safer pharmacokinetic profile compared to other statins, however, the existing preclinical evidence for its effectiveness in preeclampsia treatment has been mostly restricted to animal models...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28529325/anticancer-effects-of-the-microbiome-and-its-products
#16
REVIEW
Laurence Zitvogel, Romain Daillère, María Paula Roberti, Bertrand Routy, Guido Kroemer
The human gut microbiome modulates many host processes, including metabolism, inflammation, and immune and cellular responses. It is becoming increasingly apparent that the microbiome can also influence the development of cancer. In preclinical models, the host response to cancer treatment has been improved by modulating the gut microbiome; this is known to have an altered composition in many diseases, including cancer. In addition, cancer treatment with microbial agents or their products has the potential to shrink tumours...
May 22, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28529147/norursodeoxycholic-acid-improves-cholestasis-in-primary-sclerosing-cholangitis
#17
Peter Fickert, Gideon M Hirschfield, Gerald Denk, Hanns-Ulrich Marschall, Istvan Altorjay, Martti Färkkilä, Christoph Schramm, Ulrich Spengler, Roger Chapman, Annika Bergquist, Erik Schrumpf, Frederik Nevens, Palak Trivedi, Florian P Reiter, Istvan Tornai, Emina Halilbasic, Roland Greinwald, Markus Pröls, Michael P Manns, Michael Trauner
Primary sclerosing cholangitis (PSC) represents a devastating bile duct disease lacking effective medical therapy. 24-norursodeoxycholic acid (norUDCA) is a side chain-shortened C23 homologue of UDCA and has shown potent anti-cholestatic, anti-inflammatory and anti-fibrotic properties in a preclinical PSC mouse model. AIM: To evaluate the safety and efficacy of 3 doses of oral norUDCA (500mg/d, 1000mg/d or 1500 mg/d) compared with placebo in PSC in a RCT including 38centers from 12European countries...
May 18, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28529062/quantitative-targeted-bile-acid-profiling-as-new-markers-for-dili-in-a-model-of-methapyrilene-induced-liver-injury-in-rats
#18
Markus Slopianka, Anne Herrmann, Mira Pavkovic, Heidrun Ellinger-Ziegelbauer, Rainer Ernst, Angela Mally, Matthias Keck, Bjoern Riefke
Recently, bile acids (BAs) were reported as promising markers for drug-induced liver injury (DILI). BAs have been suggested to correlate with hepatocellular and hepatobiliary damage; however a clear connection of BA patterns with different types of DILI remains to be established. To investigate if BAs can improve the assessment of liver injury, 20 specific BAs were quantitatively profiled via LC-MS/MS in plasma and liver tissue in a model of methapyrilene-induced liver injury in rats. Methapyrilene, a known hepatotoxin was dosed daily over 14-days at doses of 30 and 80mg/kg, followed by a recovery phase of 10 days...
May 18, 2017: Toxicology
https://www.readbyqxmd.com/read/28528814/preclinical-study-using-malat1-small-interfering-rna-or-androgen-receptor-splicing-variant-7-degradation-enhancer-asc-j9-%C3%A2-to-suppress-enzalutamide-resistant-prostate-cancer-progression
#19
Ronghao Wang, Yin Sun, Lei Li, Yuanjie Niu, Wanying Lin, Changyi Lin, Emmanuel S Antonarakis, Jun Luo, Shuyuan Yeh, Chawnshang Chang
BACKGROUND: While androgen-deprivation-therapy with the recently developed antiandrogen enzalutamide (Enz) shows promising therapeutic benefits in men with metastatic castration-resistant prostate cancer (PCa), many patients develop resistance to Enz, which may involve the induction of the androgen receptor (AR) splicing variant 7 (AR-v7). OBJECTIVE: Our aim is to identify the mechanisms responsible for AR-v7 production and to develop novel preclinical approaches to suppress the Enz-resistant (EnzR) PCa...
May 18, 2017: European Urology
https://www.readbyqxmd.com/read/28528521/myeloid-populations-in-systemic-autoimmune-diseases
#20
REVIEW
María Morell, Nieves Varela, Concepción Marañón
Systemic autoimmune diseases (SADs) encompass a wide spectrum of clinical signs as a reflection of their complex physiopathology. A variety of mechanisms related with the innate immune system are in the origin of the loss of self-tolerance in these diseases, and for most of them, the myeloid leukocytes are key actors. Monocytes, macrophages, dendritic cells, and neutrophils are first-line immune effectors located in the interface between innate and adaptive immunity. They are crucial in the organization of the local and systemic responses to damage-associated molecular patterns (DAMPs) and determine the intensity, orientation, and duration of the local immune response through the expression of chemokines, costimulatory or protolerogenic factors...
May 20, 2017: Clinical Reviews in Allergy & Immunology
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