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https://www.readbyqxmd.com/read/29145505/spontaneous-development-of-epstein-barr-virus-associated-human-lymphomas-in-a-prostate-cancer-xenograft-program
#1
Alberto J Taurozzi, Ramprakash Beekharry, Michelle Wantoch, Marie-Christine Labarthe, Hannah F Walker, Robert I Seed, Matthew Simms, Greta Rodrigues, James Bradford, Geertje van der Horst, Gabri van der Pluijm, Anne T Collins
Prostate cancer research is hampered by the lack of in vivo preclinical models that accurately reflect patient tumour biology and the clinical heterogeneity of human prostate cancer. To overcome these limitations we propagated and characterised a new collection of patient-derived prostate cancer xenografts. Tumour fragments from 147 unsupervised, surgical prostate samples were implanted subcutaneously into immunodeficient Rag2-/-γC-/- mice within 24 hours of surgery. Histologic and molecular characterisation of xenografts was compared with patient characteristics, including androgen-deprivation therapy, and exome sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/29144553/blocking-17%C3%AE-hydroxysteroid-dehydrogenase-type-1-in-endometrial-cancer-a-potential-novel-endocrine-therapeutic-approach
#2
Gonda Fj Konings, Karlijn Mc Cornel, Sofia Xanthoulea, Bert Delvoux, Margaretha A Skowron, Loes Kooreman, Pasi Koskimies, Camilla Krakstad, Helga B Salvesen, Kim van Kuijk, Yannick Jm Schrooders, Marc Vooijs, Arjan J Groot, Marlies Y Bongers, Roy Fpm Kruitwagen, Andrea Romano
The enzyme type 1 17β-hydroxysteroid dehydrogenase (17β-HSD-1), responsible for generating active 17β-estradiol (E2) from low-active estrone (E1), is over-expressed in endometrial cancer (EC) thus implicating an increased intra-tissue generation of E2 in this estrogen-dependent condition. In this study we explored the possibility of inhibiting 17β-HSD-1 and impairing the generation of E2 from E1 in EC using in vitro, in vivo and ex vivo models. We generated EC cell lines derived from the well-differentiated endometrial adenocarcinoma Ishikawa cell line and expressing levels of 17β-HSD-1 similar to human tissues...
November 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29143855/considerations-and-guidelines-for-mouse-metabolic-phenotyping-in-diabetes-research
#3
REVIEW
Thierry Alquier, Vincent Poitout
Mice are the most commonly used species in preclinical research on the pathophysiology of metabolic diseases. Although they are extremely useful for identifying pathways, mechanisms and genes regulating glucose and energy homeostasis, the specificities of the various mouse models and methodologies used to investigate a metabolic phenotype can have a profound impact on experimental results and their interpretation. This review aims to: (1) describe the most commonly used experimental tests to assess glucose and energy homeostasis in mice; (2) provide some guidelines regarding the design, analysis and interpretation of these tests, as well as for studies using genetic models; and (3) identify important caveats and confounding factors that must be taken into account in the interpretation of findings...
November 16, 2017: Diabetologia
https://www.readbyqxmd.com/read/29142069/cat-02-106-a-site-specifically-conjugated-anti-cd22-antibody-bearing-an-mdr1-resistant-maytansine-payload-yields-excellent-efficacy-and-safety-in-preclinical-models
#4
Penelope M Drake, Adam Carlson, Jesse M McFarland, Stefanie Banas, Robyn M Barfield, Wesley Zmolek, Yun Cheol Kim, Betty C B Huang, Romas Kudirka, David Rabuka
Hematologically-derived tumors make up ~10% of all newly-diagnosed cancer cases in the U.S. Of these, the non-Hodgkin lymphoma (NHL) designation describes a diverse group of cancers that collectively rank among the top 10 most commonly diagnosed cancers worldwide. Although long-term survival trends are improving, there remains a significant unmet clinical need for treatments to help patients with relapsed or refractory disease, one cause of which is drug efflux through upregulation of xenobiotic pumps, such as MDR1...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29142066/characterization-of-sgn-cd123a-a-potent-cd123-directed-antibody-drug-conjugate-for-acute-myeloid-leukemia
#5
Fu Li, May Kung Sutherland, Changpu Yu, Roland B Walter, Lori Westendorf, John Valliere-Douglass, Lucy Pan, Ashley Cronkite, Django Sussman, Kerry Klussman, Michelle Ulrich, Martha E Anderson, Ivan J Stone, Weiping Zeng, Mechthild Jonas, Timothy S Lewis, Maitrayee Goswami, Sa A Wang, Peter D Senter, Che-Leung Law, Eric J Feldman, Dennis R Benjamin
Treatment choices for acute myeloid leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents are needed. Interleukin-3 receptor alpha (IL-3Rα, or CD123) is expressed on the majority of AML blasts and there is evidence that its expression is increased on leukemic relative to normal hematopoietic stem cells, which makes it an attractive target for antibody-based therapy. Here we report the generation and preclinical characterization of SGN-CD123A, an antibody-drug conjugate utilizing the pyrrolobenzodiazepine dimer (PBD) linker and a humanized CD123 antibody with engineered cysteines for site-specific conjugation...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29141970/natural-forms-of-vitamin-e-as-effective-agents-for-cancer-prevention-and-therapy
#6
REVIEW
Qing Jiang
Initial research on vitamin E and cancer has focused on α-tocopherol (αT), but recent clinical studies on cancer-preventive effects of αT supplementation have shown disappointing results, which has led to doubts about the role of vitamin E, including different vitamin E forms, in cancer prevention. However, accumulating mechanistic and preclinical animal studies show that other forms of vitamin E, such as γ-tocopherol (γT), δ-tocopherol (δT), γ-tocotrienol (γTE), and δ-tocotrienol (δTE), have far superior cancer-preventive activities than does αT...
November 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/29141948/a-phase-i-study-of-romidepsin-and-pralatrexate-reveals-marked-activity-in-relapsed-and-refractory-t-cell-lymphoma
#7
Jennifer E Amengual, Renee Lichtenstein, Jennifer Lue, Ahmed Sawas, Changchun Deng, Emily Lichtenstein, Karen Khan, Laine Atkins, Aishling Rada, Hye A Kim, Codruta Chiuzan, Matko Kalac, Enrica Marchi, Lorenzo Falchi, Mark A Francescone, Lawrence Schwartz, Serge Cremers, Owen A O'Connor
The peripheral T-cell lymphomas (PTCL) are a group of rare malignancies characterized by chemotherapy insensitivity and poor prognosis. Romidepsin and pralatrexate were approved by the U.S. FDA for patients with relapsed/refractory PTCL, exhibiting response rates of 25% and 29% respectively. Based on synergy of the combination in preclinical models of PTCL, we initiated a phase I study of pralatrexate plus romidepsin in patients with relapsed/refractory lymphoma (ClinicalTrials.gov (NCT01947140)). This was a single institution dose-escalation phase I study of pralatrexate plus romidepsin designed to determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetic profile and response rates...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29141866/prostate-specific-membrane-antigen-cleavage-of-vitamin-b9-stimulates-oncogenic-signaling-through-metabotropic-glutamate-receptors
#8
Charalambos Kaittanis, Chrysafis Andreou, Haley Hieronymus, Ninghui Mao, Catherine A Foss, Matthias Eiber, Gregor Weirich, Palak Panchal, Anuradha Gopalan, Juan Zurita, Samuel Achilefu, Gabriela Chiosis, Vladimir Ponomarev, Markus Schwaiger, Brett S Carver, Martin G Pomper, Jan Grimm
Prostate-specific membrane antigen (PSMA) or folate hydrolase 1 (FOLH1) is highly expressed on prostate cancer. Its expression correlates inversely with survival and increases with tumor grade. However, the biological role of PSMA has not been explored, and its role in prostate cancer remained elusive. Filling this gap, we demonstrate that in prostate cancer, PSMA initiates signaling upstream of PI3K through G protein-coupled receptors, specifically via the metabotropic glutamate receptor (mGluR). PSMA's carboxypeptidase activity releases glutamate from vitamin B9 and other glutamated substrates, which activate mGluR I...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29141689/patient-derived-xenograft-in-zebrafish-embryos-a-new-platform-for-translational-research-in-gastric-cancer
#9
Jia-Qi Wu, Jing Zhai, Chong-Yong Li, Ai-Min Tan, Ping Wei, Li-Zong Shen, Ming-Fang He
BACKGROUND: Gastric cancer (GC) is among the most commonly cancer occurred in Asian, especially in China. With its high heterogeneity and few of validated drug targets, GC remains to be one of the most under explored areas of precision medicine. In this study, we aimed to establish an in vivo patient-derived xenograft (PDX) model based on zebrafish (Danio rerio) embryos, allowing for a rapid analysis of the angiogenic and invasive potentials, as well as a fast drug sensitivity testing...
November 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29141529/experimental-autoimmune-encephalomyelitis-eae-model-of-cynomolgus-macaques-induced-by-recombinant-human-mog1-125-rhmog1-125-protein-and-mog34-56-peptide
#10
Yunxiao Sun, Zhen Peng, Libiao Zhang, Huaqian Wang, Xiangyang He, Xingwen Peng, Qin Zhang, Hui Liu, Junhua Rao, Haifeng Wang, Jie Wu
Experimental autoimmune encephalomyelitis (EAE) induced by self-myelin antigen is a widely used multiple sclerosis (MS) model for preclinical studies of new therapeutics and potential pathogenesis. By comparison with rodent EAE models, EAE models in primates are more similar to MS. Some groups have developed EAE models in primates by using common marmoset (Callithrix jacchus). However, this model has some limitations. EAE in cynomolgus monkey (Macaque fasciculrais) could overcome these limitations. In this study, EAE was induced in cynomolgus monkey by immunizing with the recombinant human myelin oligodendrocyte glycoprotein extracellular domain (1-125) (rhMOG1-125) and a synthetic peptide, representing peptide 34-56 of human myelin oligodendrocyte glycoprotein (MOG34-56) in complete Freund's adjuvant (CFA) and in combination with intravenous injection of pertussis toxin, and subsequent booster immunizations with the same dose of antigen in incomplete Freund's adjuvant (IFA) until the animals developed clinically significant EAE (score≥2)...
November 9, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29141501/transient-hypertension-after-spinal-cord-injury-leads-to-cerebrovascular-endothelial-dysfunction-and-fibrosis
#11
Aaron A Phillips, Nusrat Matin, Mengyao Jia, Jordan W Squair, Aaron Monga, Mei Mu Zi Zheng, Rahul Sachdeva, Andrew Yung, Shea Hocolaski, Stacy L Elliott, Piotr Kozlowski, Anne Dorrance, Ismail Laher, Phil Ainslie, Andrei V Krassioukov
We aimed to create a clinically-relevant preclinical model of transient hypertension, and then evaluate the pathophysiological cerebrovascular processes resulting from this novel stimulus, which has recently been epidemiologically linked to cerebrovascular disease. We first developed a clinically-relevant model of transient hypertension, secondary to induced autonomic dysreflexia after spinal cord injury, and demonstrated that in both patients and rats this stimulus leads to drastic acute cerebral hyper-perfusion...
November 15, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29141027/the-efficacy-of-chimeric-antigen-receptor-car-immunotherapy-in-animal-models-for-solid-tumors-a-systematic-review-and-meta-analysis
#12
Yingcheng Wu, Ran Xu, Keren Jia, Hui Shi
BACKGROUND: Most recently, an emerging theme in the field of tumor immunology predominates: chimeric antigen receptor (CAR) therapy in treating solid tumors. The number of related preclinical trials was surging. However, an evaluation of the effects of preclinical studies remained absent. Hence, a meta-analysis was conducted on the efficacy of CAR in animal models for solid tumors. METHODS: The authors searched PubMed/Medline, Embase, and Google scholar up to April 2017...
2017: PloS One
https://www.readbyqxmd.com/read/29138752/the-effect-of-granulocyte-colony-stimulating-factor-on-the-progression-of-atherosclerosis-in-animal-models-a-meta-analysis
#13
REVIEW
Manli Liu, Kejian Liu, Dongdong Chen, Hongzhi Chen, Kunming Sun, Xinxin Ju, Jiaojiao Lan, Yang Zhou, Weishan Wang, Lijuan Pang
Background: Atherosclerosis is a common inflammatory disease. Stem cell and endothelial progenitor cell treatments can improve cardiac function after myocardial infarction. Granulocyte colony-stimulating factor (G-CSF) is a mobilisation agent, mobilising stem cells from the bone marrow to circulation in the blood. G-CSF may constitute a treatment of atherosclerosis. We have conducted meta-analysis to evaluate the current evidence for the effect of G-CSF on the progression of atherosclerosis in animal models and to provide reference for preclinical experiments and future human clinical trials of atherosclerosis treatment...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29138581/puma-mediates-the-anti-cancer-effect-of-osimertinib-in-colon-cancer-cells
#14
Lingchuan Guo, Shan Huang, Xinwei Wang
Osimertinib, an irreversible EGFR/HER2 inhibitor, has been found to be effective in the cancer cell with EGFR gene mutations in preclinical lung cancer models. However, the effect of osimertinib in colorectal cancer (CRC) cells is unclear. In the present study, we investigated how osimertinib suppresses CRC cells growth and potentiates effects of other chemotherapeutic drugs. We found that p73-mediated osimertinib-induced p53 upregulated modulator of apoptosis (PUMA) expression irrespective of p53 status following PI3K/AKT pathway inhibition in CRC cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29137981/umbilical-cord-derived-mesenchymal-stem-cells-alleviated-inflammation-and-inhibited-apoptosis-in-interstitial-cystitis-via-akt-mtor-signaling-pathway
#15
Juncong Xie, Bolong Liu, Jialiang Chen, Yuancheng Xu, Hailun Zhan, Fei Yang, Wenbiao Li, Xiangfu Zhou
Interstitial cystitis (IC) is a bladder syndrome characterized by pelvic pain and urinary frequency without infection or other identifiable pathology. There are no effective treatments to cure IC. This study investigated the effects of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) injection on IC rat model. Furthermore, we used a coculture system to find the possible molecular mechanism on the human uroepithelial cells (SV-HUC-1), which was the cell model of IC. A rat model of IC was established via systemic injection with cyclophosphamide (CYP) and a cell model of IC was induced by being exposed to tumor necrosis factor (TNF)-α (10 ng/ml)...
November 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29137451/the-transcription-factor-atf5-role-in-cellular-differentiation-stress-responses-and-cancer
#16
REVIEW
Thomas K Sears, James M Angelastro
Activating transcription factor 5 (ATF5) is a cellular prosurvival transcription factor within the basic leucine zipper (bZip) family that is involved in cellular differentiation and promotes cellular adaptation to stress. Recent studies have characterized the oncogenic role of ATF5 in the development of several different types of cancer, notably glioblastoma. Preclinical assessment of a systemically deliverable dominant-negative ATF5 (dnATF5) biologic has found that targeting ATF5 results in tumor regression and tumor growth inhibition of glioblastoma xenografts in mouse models...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137221/anti-pancreatic-cancer-activity-of-onc212-involves-the-unfolded-protein-response-upr-and-is-reduced-by-igf1-r-and-grp78-bip
#17
Avital Lev, Amriti R Lulla, Jessica Wagner, Marie D Ralff, Joshua B Kiehl, Yan Zhou, Cyril H Benes, Varun V Prabhu, Wolfgang Oster, Igor Astsaturov, David T Dicker, Wafik S El-Deiry
Pancreatic cancer is chemo-resistant and metastasizes early with an overall five-year survival of ∼8.2%. First-in-class imipridone ONC201 is a small molecule in clinical trials with anti-cancer activity. ONC212, a fluorinated-ONC201 analogue, shows preclinical efficacy in melanoma and hepatocellular-cancer models. We investigated efficacy of ONC201 and ONC212 against pancreatic cancer cell lines (N=16 including 9 PDX-cell lines). We demonstrate ONC212 efficacy in 4 in-vivo models including ONC201-resistant tumors...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137110/neobomb1-a-grpr-antagonist-for-breast-cancer-theragnostics-first-results-of-a-preclinical-study-with-67-ga-neobomb1-in-t-47d-cells-and-tumor-bearing-mice
#18
Aikaterini Kaloudi, Emmanouil Lymperis, Athina Giarika, Simone Dalm, Francesca Orlandi, Donato Barbato, Mattia Tedesco, Theodosia Maina, Marion de Jong, Berthold A Nock
The GRPR-antagonist-based radioligands [(67/68)Ga/(111)In/(177)Lu]NeoBOMB1 have shown excellent theragnostic profiles in preclinical prostate cancer models, while [(68)Ga]NeoBOMB1 effectively visualized prostate cancer lesions in patients. We were further interested to explore the theragnostic potential of NeoBOMB1 in GRPR-positive mammary carcinoma, by first studying [(67)Ga]NeoBOMB1 in breast cancer models; Methods: We investigated the profile of [(67)Ga]NeoBOMB1, a [(68)Ga]NeoBOMB1 surrogate, in GRPR-expressing T-47D cells and animal models; Results: NeoBOMB1 (IC50s of 2...
November 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29136276/targeted-therapies-immunologic-effects-and-potential-applications-outside-of-cancer
#19
REVIEW
Anna E Kersh, Spencer Ng, Yun Min Chang, Maiko Sasaki, Susan N Thomas, Haydn T Kissick, Gregory B Lesinski, Ragini R Kudchadkar, Edmund K Waller, Brian P Pollack
Two pharmacologic approaches that are currently at the forefront of treating advanced cancer are those that center on disrupting critical growth/survival signaling pathways within tumor cells (commonly referred to as "targeted therapies") and those that center on enhancing the capacity of a patient's immune system to mount an antitumor response (immunotherapy). Maximizing responses to both of these approaches requires an understanding of the oncogenic events present in a given patient's tumor and the nature of the tumor-immune microenvironment...
November 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29136236/basic-neuroscience-illuminates-causal-relationship-between-sleep-and-memory-translating-to-schizophrenia
#20
Ana Pocivavsek, Laura M Rowland
Patients with schizophrenia are often plagued by sleep disturbances that can exacerbate the illness, including potentiating psychosis and cognitive impairments. Cognitive dysfunction is a core feature of schizophrenia with learning and memory being particularly impaired. Sleep disruptions often accompanying the illness and may be key mechanism that contribute to these core dysfunctions. In this special translational neuroscience feature, we highlight the role of sleep in mediating cognitive function, with a special focus on learning and memory...
November 9, 2017: Schizophrenia Bulletin
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