• vitro
  • OcellO, a Netherlands-based contract research organization that offers drug screening and profiling services using 3D cell culture models of disease, says it has expanded the utility of patient-derived (PDX) mouse models by offering in vitro assays using 3D culture of the same tumor materials. (genengnews.com)
  • Despite technical obstacles, Dr. Price cited advantages of the company's high-throughput in vitro PDX screening platform: the supply of PDX tumor is essentially unlimited in amount, and the same tumor can be sourced repeatedly "[This is] unlike patient tumor, which is limited in amount and can only be obtained once," he points out. (genengnews.com)
  • Dr. Price also noted that a major headache in drug discovery is the translation between in vitro and in vivo studies-results of in vitro studies with cell lines can often not be recapitulated in vivo , partly because the biology of a 2D monolayer and a solid tumor are different and because the cell lines used in vitro differ from the tumors in mice. (genengnews.com)
  • He also described examples of where an unexpected drug sensitivity observed in in vivo PDX studies was recapitulated in the company's in vitro PDX model. (genengnews.com)
  • Thus, the in vitro cellular potency, together with in vivo antitumor activity, confirms the potential of P276-00, a cyclin-dependent kinase inhibitor as an anticancer molecule. (aacrjournals.org)
  • However, there is currently no in vitro assay to measure the impact of such blockade on cytokine secretion in cells from human samples. (jove.com)
  • The discovery of small chemical inhibitors of human Kinesin-5 through a pioneering in vitro phenotypic screening on cancer cell lines has led to both the development of new anticancer therapeutic agents, and to novel tools to probe the mechanism of microtubule motor proteins. (wikipedia.org)
  • inhibitors
  • The effects of the strongest inhibitors were validated in a panel of angiogenesis assays, including proliferation, migration, tube formulation and chorioallantoic membrane assay. (smi-online.co.uk)
  • Negative correlations between 7-ethoxycoumarin O -deethylation and cell line chemosensitivity to a group of topoisomerase inhibitors were also seen, again suggesting P450-dependent drug inactivation. (aspetjournals.org)
  • CDKs have also been the targets of numerous molecular screening studies designed to identify low molecular weight pharmacologic inhibitors with potential use against various human diseases derived from abnormal cell cycle regulation (review in ref. 4 ). (aacrjournals.org)
  • Among these, ( R )-roscovitine was initially identified in a CDK1/cyclin B screen ( 22 ) and proven to be one of the first selective CDK inhibitors. (aacrjournals.org)
  • mTOR inhibitors are a class of drugs that inhibit the mechanistic target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). (wikipedia.org)
  • therapeutic
  • To design new therapeutic strategies and to test the efficacy of antiangiogenic cancer drugs, researchers and clinicians need models in which these malignant angiogenic events can be replicated and then studied at genetic, biochemical, molecular, and cellular levels. (ahajournals.org)
  • In the case of antitumor prodrugs, such as cyclophosphamide and ifosfamide, P450 metabolism is essential for therapeutic activity ( Sladek, 1994 ). (aspetjournals.org)
  • The aim of this study was to identify a target range for inosin-5-monophosphate dehydrogenase (IMPDH) activity in maintenance therapy with tacrolimus (TCL), and to apply the measurement of IMPDH activity to the therapeutic drug monitoring for mycophenolate mofetil (MMF). (jove.com)
  • This model serves as the groundwork for future therapeutic strategies aimed at reducing and potentially eliminating the need for chronic multi-drug immunosuppression in VCA. (jove.com)
  • Drugs that inhibit hepatic glucuronidation, such as indomethacin, nordazepam, acetylsalicylic acid (aspirin) and trimethoprim decreased the elimination rate and increased the therapeutic strength of the medication. (wikipedia.org)
  • cellular
  • At Cambridge Healthtech Institute's 15th annual High-Content Analysis and 3D Screening meeting, held November 2017 in Boston, participants from academia and pharma companies will focus on advancements in HCA technologies and applications, including screening of 3D and physiologically relevant cellular models, data analysis techniques, and will present case studies and strategies for successful drug discovery. (genengnews.com)
  • We have developed a simple screening method for the cellular activities of terpene synthases by scoring their substrate consumption based on the color loss of the cell harboring carotenoid pathways. (jove.com)
  • Based on the natural high affinity of folate for the folate receptor protein (FR), which is commonly expressed on the surface of many human cancers, folate-drug conjugates also bind tightly to the FR and trigger cellular uptake via endocytosis. (wikipedia.org)
  • clinical
  • Determine prospectively the predictive value of the EDR assay relative to clinical outcome by correlating assay results with clinical tumor response and time to tumor progression during paclitaxel therapy in these patients. (clinicaltrials.gov)
  • Patients' clinical response to paclitaxel therapy is compared with the response predicted by the EDR assay. (clinicaltrials.gov)
  • We here report that the FDA-approved anthelmintic drug nitazoxanide could be a potential candidate for advancement into cancer clinical trials. (aacrjournals.org)
  • The availability of compound libraries containing drugs with documented clinical use makes unbiased screening for repositioning candidates an attractive approach. (aacrjournals.org)
  • Phase I clinical studies revealed limited toxicity of roscovitine ( 36 ), but both preclinical studies using various animal tumor models and phase I/II clinical trials revealed that high doses of ( R )-roscovitine were required to generate antitumor activities ( 9 , 36 , 38 ). (aacrjournals.org)
  • Despite favorable and highly encouraging early and intermediate functional outcomes, rejection of the highly immunogenic skin component of a VCA and potential adverse effects of chronic multi-drug immunosuppression continue to hamper widespread clinical application of VCA. (jove.com)
  • Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. (mdpi.com)
  • The discovery of vitamin-mediated drug targeting in plants led to the hypothesis that folate-targeted therapies could be of clinical use. (wikipedia.org)
  • sensitivity
  • Studies to show tumor sensitivity using clonogenic assay in 22 human xenografts indicated that P276-00 was ∼26-fold more potent than cisplatin, and further, it was also found to be active against cisplatin-resistant tumors of central nervous system, melanoma, prostate, and renal cancers. (aacrjournals.org)
  • systemic
  • Importantly, the use of drugs (whether chemotherapy, hormonal therapy or targeted therapy) constitutes systemic therapy for cancer in that they are introduced into the blood stream and are therefore in principle able to address cancer at any anatomic location in the body. (wikipedia.org)
  • inhibition
  • However, measuring the inhibition of viral replication in cell cultures using reduction of cytopathic effects as a readout still represents a paramount screening strategy. (jove.com)
  • efficacy
  • A variation on the technique based on drug-eluting beads (DEB-TACE) has recently entered the clinic, but trials of its safety and efficacy have given conflicting results. (jove.com)
  • detection
  • Applications discussed range from measurement of slow oxidative degradation of polymers and instability of hazardous industrial chemicals to detection of bacteria in urine and evaluation of the effects of drugs on parasitic worms. (wikipedia.org)
  • molecule
  • Nitazoxanide, an FDA-approved antiprotozoal drug with excellent pharmacokinetic and safety profile, is the only molecule among the screening hits that reaches high plasma concentrations persisting for up to a few hours after single oral dose. (aacrjournals.org)
  • chemotherapy
  • RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. (clinicaltrials.gov)
  • In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. (mdpi.com)
  • Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs), or it may aim to prolong life or to reduce symptoms (palliative chemotherapy). (wikipedia.org)
  • Many of the side effects of chemotherapy can be traced to damage to normal cells that divide rapidly and are thus sensitive to anti-mitotic drugs: cells in the bone marrow, digestive tract and hair follicles. (wikipedia.org)
  • Because of the effect on immune cells (especially lymphocytes), chemotherapy drugs often find use in a host of diseases that result from harmful overactivity of the immune system against self (so-called autoimmunity). (wikipedia.org)
  • Induction chemotherapy is the first line treatment of cancer with a chemotherapeutic drug. (wikipedia.org)
  • Combined modality chemotherapy is the use of drugs with other cancer treatments, such as surgery, radiation therapy, or hyperthermia therapy. (wikipedia.org)
  • Intensification chemotherapy is identical to consolidation chemotherapy but a different drug than the induction chemotherapy is used. (wikipedia.org)
  • Combination chemotherapy involves treating a patient with a number of different drugs simultaneously. (wikipedia.org)
  • interactions
  • Silatecans or 7-silylcampthothecins have shown reduced drug-HSA interactions which contributes to its blood stability and they can also cross the blood brain barrier. (wikipedia.org)
  • cancer
  • Drug discovery remains to be the main focus for biomedical research and represents the essence of antiangiogenesis cancer research. (ahajournals.org)
  • The cancer drug development process has become increasingly costly and inefficient resulting in few new highly effective drugs reaching the market yearly ( 1 ). (aacrjournals.org)
  • discovery
  • New strategies for drug discovery are therefore urgently needed. (aacrjournals.org)
  • These platforms such as organ-on-a-chip, biological scaffolding, or microdrop techniques offer substantial advantages in evaluating disease mechanisms, drug discovery, and toxicity testing and potentially, for tissue-replacement therapies. (genengnews.com)
  • processes
  • 11 , 12 To design drugs that can be used to block such malignant processes, recent advanced strategies were aimed to better understand tumor vessels formation and normalization. (ahajournals.org)
  • Therefore, in order to be sure what process or processes are producing the measured heat flow, great care must be taken in both experimental design and in the initial use of related chemical, physical and biologic assays. (wikipedia.org)
  • development
  • Such functional screens have been greatly improved by the development of recombinant viruses expressing reporter enzymes capable of bioluminescence such as luciferase. (jove.com)
  • identification
  • Due to the improvement on methods for isolation, identification, and synthesis during the last century, many drugs have arisen from natural sources. (hindawi.com)
  • In the 1990s there was a dramatic change in this field due to studies on the mechanism of action of rapamycin and the identification of the drug target. (wikipedia.org)
  • cell
  • Tetramer assays are used for single-cell phenotyping and cell counting, and offer an important advantage over other methods, such as ELISPOT and single-cell PCR because they enable the recovery and further study of sorted cells. (wikipedia.org)
  • From a mechanistic perspective, the FR functions to concentrate exogenous ligands (e.g. folates and folate-drug conjugates) into the cell cytosol by endocytosis. (wikipedia.org)
  • studies
  • To date, the majority of the antiangiogenesis drug studies have been performed using endothelial cells isolated from either capillaries or large vessels. (ahajournals.org)
  • shows
  • A competitive assay shows that, compared with ( R )-roscovitine, N-&-N1 has reduced affinity for Erk2 and pyridoxal kinase. (aacrjournals.org)
  • specific
  • We also report the possibility for substrate-specific screening system of terpene synthases by taking advantage of the substrate-size specificity of C30 and C40 carotenoid pathways. (jove.com)
  • Targeted drug therapy is advantageous because it deposits the drug at the specific location where it can be most useful in treating the disease. (wikipedia.org)
  • human
  • P450 enzymes are highly expressed in human liver and in certain extrahepatic tissues and have been studied extensively with respect to their roles in drug metabolism ( Rendic and Di Carlo, 1997 ). (aspetjournals.org)