Abstract:
:The cancer stem cell paradigm, the epithelial-to-mesenchymal transition and its converse, the mesenchymal-to-epithelial transition, have reached convergence. Implicit in this understanding is the notion that cancer cells can change state, and with such change come bidirectional alterations in motility, proliferative activity, and drug resistance. As such, tumors present a moving target for antineoplastic therapy. This article will review the evolving adult stem cell paradigm and how changes in our understanding of the bidirectional nature of cancer cell differentiation may affect the selection and timing of antineoplastic therapy. The goal is to determine how to best administer therapies potentially targeted against the cancer stem cell state in the context of established treatment regimens, and to evaluate long-term effects beyond tumor regression.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Donnenberg VS,Donnenberg ADdoi
10.1002/jcph.486subject
Has Abstractpub_date
2015-06-01 00:00:00pages
603-19issue
6eissn
0091-2700issn
1552-4604journal_volume
55pub_type
杂志文章,评审abstract::Ustekinumab, a human immunoglobulin G1 kappa (IgG1k) monoclonal antibody that binds with high affinity to human interleukin-12 and interleukin-23, has demonstrated efficacy in patients with psoriasis. The objective of this study was to perform exposure-response modeling to increase the understanding of reduction in di...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1177/0091270009343695
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abstract::A decrease in dietary protein intake lowers the clearance of a number of substances excreted principally by the kidney including uric acid and oxypurinol, the major metabolite of allopurinol. We studied the kinetics of uric acid and oxypurinol in seven healthy volunteers on a normal protein diet (2600 calories; 100 g ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
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abstract::Unresolved issues of ethical, methodological, and legal concerns in the use of normal healthy volunteers persist. Financial incentives in their recruitment offer a unique ethical dilemma because of questions surrounding payment. A review of literature was conducted to obtain research systematically examining volunteer...
journal_title:Journal of clinical pharmacology
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doi:
更新日期:2002-04-01 00:00:00
abstract::A double-blind controlled trial was carried out to compare the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), and placebo on cholesterol and triglyceride levels in patients with endogenous hypertriglyceridemias. The dose of both bile acids was four 150-mg capsules day. Total serum cholesterol le...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1981-10-01 00:00:00
abstract::Nonlinearities are commonplace in pharmacokinetics and most frequently occur because of a limited concentration of biological material available for interaction with relatively high concentrations of drugs. The Michaelis-Menten-type function can be applied to metabolism, transport, and binding phenomena that display c...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/j.1552-4604.1989.tb03369.x
更新日期:1989-06-01 00:00:00
abstract::The bioavailability and pharmacologic activity of tablets containing micronized spironolactone chemical (median particle size 2.21 micrometers) were compared to those of tablets made from standard spironolactone chemical (median particle size 78.8 micrometers) in healthy men. Apart from particle size, all features of ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1982.tb02694.x
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abstract::The purpose of this open-label, parallel-group study was to investigate the effect of severe renal impairment on the pharmacokinetics (PK), tolerability, and safety of clazosentan, an intravenous endothelin receptor antagonist. Clazosentan was administered as a continuous intravenous infusion of 1 mg/h for a period of...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/0091270010368975
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abstract::The analgesic activity of buprenorphine was monitored versus that of morphine in a double-blind, randomized, multiple-dose, parallel-design study involving 97 postsurgical patients. Patients could receive intramuscular injections of either buprenorphine (0.3, o.45, or 0.6 mg) or morphine (10, 15, or 20 mg) every 3 or ...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1982-04-01 00:00:00
abstract::Effective and practical preventive procedures for postflight orthostatic intolerance are highly desirable. The current practice of attempts to expand plasma volume by ingestion of salt and fluids before reentry has proven benefits. This study evaluated alternative options using fludrocortisone (F) to expand plasma vol...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1991.tb03659.x
更新日期:1991-10-01 00:00:00
abstract::The differential diagnosis of idiosyncratic adverse drug reactions (ADRs) is difficult because symptoms are seldom pathognomonic. The authors compared the performance of two new diagnostic aids in the differential diagnosis of 27 cases of skin reactions associated with sulfonamide therapy. One test, the Bayesian Adver...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1994.tb04736.x
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abstract::The pharmacokinetics and safety of a single oral dose of 200-mg plant-derived pharmaceutical formulation of highly purified cannabidiol (CBD) in oral solution (Epidiolex in the United States; 100 mg/mL) were assessed in subjects with mild to severe hepatic impairment (n = 8 each for mild and moderate, n = 6 for sever...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
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abstract::Tissue pharmacokinetics and plasma protein binding of colistin have not been described in humans in vivo. Colistin concentrations in plasma, muscle, and subcutis of healthy volunteers were measured by microdialysis after a single dose of 2.5 million IU of colistin methanesulfonate. In vitro microdialysis experiments a...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:2015-04-01 00:00:00
abstract::Drug dosing in renal insufficiency needs to be individualized whenever possible to optimize therapeutic outcomes and to minimize toxicity. Although a number of published tables that provide dosing guidelines and nomograms exist to assist in dose modification, individualization of therapy should be based on pharmacokin...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1994.tb03973.x
更新日期:1994-02-01 00:00:00
abstract::A pilot study of a small group of schizophrenic patients manifesting symptoms of a depressive nature was treated in a double-blind study in which viloxazine or a placebo was administered in combination with either chlorpromazine or haloperidol. There appeared to be no difference between the viloxazine-treated group an...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1981-01-01 00:00:00
abstract::Although physiologic modeling has not gained the widespread acceptance that was originally projected, it may serve as the basis for future PK/PD modeling approaches. In addition, with more effort applied to developing in vitro and animal-to-human predictions, physiologic modeling may assume a higher position in the ph...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/j.1552-4604.1988.tb03199.x
更新日期:1988-08-01 00:00:00
abstract::Bile acid sequestrants can potentially bind to concomitant drugs. Single-dose studies evaluated the effects of colesevelam on the pharmacokinetics of glimepiride, glipizide extended-release (ER), and olmesartan medoxomil. Each study enrolled healthy subjects aged 18-45 years. The olmesartan medoxomil study used a rand...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
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abstract::Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor and an inhibitor of UDP-glucuronosyltransferase-1A1 (UGT1A1), which is involved in raltegravir clearance. Raltegravir, an HIV integrase inhibitor, may be used in combination with HCV treatment in HCV/HIV co-infected patients. In this open-label,...
journal_title:Journal of clinical pharmacology
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doi:10.1002/jcph.418
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abstract::The authors evaluated the effect of high-dose aspirin at a therapeutic dose, using chlorzoxazone as a probe for CYP2E1 enzyme activity. In a randomized, open-label, 2-way crossover study, 10 healthy men were treated 3 times daily for 6 days with 1 g aspirin or placebo. On day 7, 1 dose of 400 mg chlorzoxazone was admi...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, approved for second-line therapy for advanced renal cell carcinoma (RCC). Axitinib population pharmacokinetic and pharmacokinetic/pharmacodynamic relationships were evaluated. Using nonlinear mixed effects modelin...
journal_title:Journal of clinical pharmacology
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abstract::The pharmacokinetics and pharmacodynamics of flunisolide were studied in healthy volunteers after inhalation. In the morning on the day the study began, volunteers inhaled 0.5 mg of flunisolide with and without oral administration of charcoal, or 1 mg, 2 mg, and 3 mg of flunisolide with concomitant administration of c...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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abstract::A reflectance spectrophotometric method for evaluation of the skin blanching response to topical corticosteroids was evaluated. This blanching response is used, for drug development and regulatory purposes, to assess potency and bioequivalence of topical corticosteroid products. The common method involves the use of a...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1993.tb05611.x
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abstract::Microdialysis is a technique that allows the measurement of free antibiotic concentrations in different tissues, which are responsible for the antibacterial activity at the infection site. In an open, randomized, 2-way crossover study in healthy volunteers, the muscle penetration of orally administered cefpodoxime (40...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::A single blind crossover study with washout phases showed that pyrazinoylguanidine (PZG) reduced elevated serum concentrations of urea, triglycerides, and cholesterol in patients with renal insufficiency. Pyrazinoylguanidine was saluretic, without affecting serum potassium or glucose concentrations. The onset of PZG's...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1993.tb04703.x
更新日期:1993-06-01 00:00:00
abstract::In the Phase I study, the new anthracycline aclacinomycin A was given to 22 advanced cancer patients on a schedule of daily intravenous administration for five days repeated every four weeks. The limiting toxicity was myelosuppression, which was severe at a dose of 30 mg/m2 per day for five days. Platelet nadirs were ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1982.tb02686.x
更新日期:1982-08-01 00:00:00
abstract::Renal electrolyte excretion patterns were determined in nonedematous healthy volunteers following bumetanide and furosemide in two separate clinical studies. In study 1, intravenous bumetanide was administered to 24 subjects at four dose levels. In study 2, bumetanide (1 or 2 mg) or furosemide (40 or 80 mg) was admini...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/j.1552-4604.1981.tb05671.x
更新日期:1981-11-01 00:00:00
abstract::Enalapril maleate (MK-421) is a new non-sulfhydryl-containing converting-enzyme inhibitor that has been shown to be effective and well tolerated in patients with essential hypertension. Data on its effectiveness and safety in patients with renovascular hypertension are limited and have involved predominantly short-ter...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/009127008702700105
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abstract::The antihypertensive effect of a new beta-adrenergic receptor blocker, l-bunolol, was evaluated in 11 hospitalized hypertensive patients of whom four belonged to the high-renin, five to the normal-renin, and two to the low-renin subgroup. There was a significant decrease in blood pressure in most patients, often to no...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1977-05-01 00:00:00
abstract::Abetimus sodium is an oligonucleotide-based investigational drug designed to treat patients with lupus nephritis by specifically reducing anti-double-stranded DNA antibody levels. The safety and pharmacokinetics of abetimus were evaluated in 24 healthy volunteers at intravenous doses of 600 mg, 1200 mg, and 2400 mg. T...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
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abstract::Disease states such as liver cirrhosis and chronic kidney disease can lead to altered pharmacokinetics (PK) of drugs by influencing drug absorption, blood flow to organs, plasma protein binding, apparent volume of distribution, and drug-metabolizing enzyme and transporter (DMET) abundance. Narrow therapeutic index dru...
journal_title:Journal of clinical pharmacology
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abstract::Chemotherapy-induced nausea and vomiting (CINV) is a common treatment-related adverse event that negatively impacts the quality of life of cancer patients. During pediatric drug development, extrapolation of efficacy from adult to pediatric populations is a pathway that can minimize the exposure of children to unneces...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:2020-06-01 00:00:00