Abstract:
PURPOSE:We have shown that the three human prostate xenograft tumors, i.e. the androgen-dependent CWR22 tumor, and the androgen-resistant CWR22R and CWR91 tumors, are comparable to patient tumors in their expression of prostate specific antigen, multidrug resistance p-glycoprotein, p53 and Bcl-2 and in their sensitivity to doxorubicin and paclitaxel. The present study used histocultures of these xenograft tumors to evaluate the antiproliferative and cytotoxic effects of several drugs (geldanamycin, cytochalasin E and thiacetazone), which have diverse action mechanisms and have shown activity against primary cultures of human prostate cancer cells. Suramin, a clinically active compound was included for comparison. Methods. The antiproliferative effect of 96 h drug treatment was measured by inhibition of DNA precursor incorporation, and the cytotoxic or cell kill effect was measured by in situ DNA end labeling of apoptotic and necrotic cells and by reduction of live cell density. RESULTS:The rank order of molar potency was geldanamycin > cytochalasin E > suramin > or = thiacetazone. Thiacetazone produced antiproliferation only in CWR22 tumor and had no cytotoxicity, whereas the other three drugs produced both antiproliferation and cytotoxicity in all three tumors. Geldanamycin, but not cytochalasin E and suramin, showed greater antiproliferation and cytotoxicity in tumor cells compared to normal stromal cells. The two androgen-resistant tumors were 4 to >40-fold less sensitive than the androgen-dependent tumor to drug-induced antiproliferation but were about equally or 4 to >20-fold more sensitive to drug-induced cytotoxicity. The ratios of drug concentrations that produced 50% antiproliferation to the concentrations that produced 50% cytotoxicity ranged from <0.04 to 0.3 in CWR22 tumor, but ranged from 0.3 to 2.7 in CWR22R and CWR91 tumors, indicating a shift from antiproliferation as the predominant drug effect in the androgen-dependent tumor to cytotoxicity in the androgen-resistant tumors. CONCLUSIONS:Our results indicate (a) differential drug effects in human prostate xenograft tumors with antiproliferation and cytotoxicity as the predominant drug effect in the androgen-dependent and androgen-resistant tumors, respectively, (b) that progression of tumors from androgen-dependent state to androgen-resistant state appears to be associated with a lower sensitivity to drug-induced antiproliferation and an equal or greater sensitivity to drug-induced cytotoxicity, and (c) that geldanamycin but not thiacetazone warrants further development.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Gan Y,Au JL,Lu J,Wientjes MGdoi
10.1023/a:1011921031564subject
Has Abstractpub_date
1998-11-01 00:00:00pages
1760-6issue
11eissn
0724-8741issn
1573-904Xjournal_volume
15pub_type
杂志文章abstract:PURPOSE:To determine the effect of Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) on the permeation of cromolyn across Caco-2 cell monolayers and explore the molecular basis for the enhanced absorption. METHODS:Transport studies of cromolyn across Caco-2 cell monolayers were conducted in the presence of various ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-004-7671-9
更新日期:2004-12-01 00:00:00
abstract:PURPOSE:To characterize the uptake mechanism of zidovudine (AZT), a nucleoside reverse transcriptase inhibitor, in syncytiotrophoblast cells using the TR-TBT 18d-1 cell line previously established by our group. MATERIALS AND METHODS:The effects of several transporter inhibitors on the initial and steady-state apical u...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9564-9
更新日期:2008-07-01 00:00:00
abstract::Silk is a remarkable biopolymer with a long history of medical use. Silk fabrications have a robust track record for load-bearing applications, including surgical threads and meshes, which are clinically approved for use in humans. The progression of top-down and bottom-up engineering approaches using silk as the basi...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-018-2534-y
更新日期:2018-11-05 00:00:00
abstract:PURPOSE:The purpose of this study is to investigate the characteristics of pGlu-L-Dopa-Pro as a prodrug of L-Dopa. METHODS:pGlu-L-Dopa-Pro and L-Dopa-Pro were synthesized using the standard procedures of peptide synthesis. The conversion of pGlu-L-Dopa-Pro to L-Dopa was studied using pyroglutamyl aminopeptidase I and ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016239321494
更新日期:1995-07-01 00:00:00
abstract::Some geminal bisphosphonates are used clinically for a number of important bone/calcium related diseases; however, side effects and lack of selectivity impede their wide use. This work reports the synthesis and evaluation of bisacylphosphonates (e.g., adipoyl- and suberoylbisphosphonate). These compounds were found to...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018956516640
更新日期:1992-01-01 00:00:00
abstract::Sodium taurodihydrofusidate (STDHF) is one of the most promising absorption enhancers for nasal delivery of peptide drugs. Drugs and additives in nasal formulations should not interfere with the self-cleaning capacity of the nose by the ciliary epithelium. Measured in vitro on human adenoid tissue with a photoelectric...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015872617511
更新日期:1990-02-01 00:00:00
abstract:PURPOSE:The use of dendrimers for biomedical applications has emerged with promising results. 2G-NN16 is a carbosilane dendrimer with sixteen positive charges per molecule tested to be capable to bind and release antisense oligonucleotides (ODNs) and small interference RNA (siRNA) in vitro. In spite of low cytotoxicity...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9776-z
更新日期:2009-03-01 00:00:00
abstract:PURPOSE:This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa. METHODS:Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate g...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2464-8
更新日期:2018-08-09 00:00:00
abstract:PURPOSE:Novel multidrug resistance (mdr) modulators have been proved as inhibitors of P-glycoprotein (P-gp). We first investigated the in vitro effects of selected compounds in human cancer cells on multidrug resistance reversal effects compared to drug standards and on P-gp induction to characterize the potential of t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9736-7
更新日期:2009-01-01 00:00:00
abstract:PURPOSE:Polyethylenimine (PEI) is a highly effective gene delivery vector, but because it is an off-the shelf material, its properties may not be optimal. To investigate the effects of the protonation properties of the polymer, we generated PEI derivatives by acetylating varying fractions of the primary and secondary a...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000016251.42392.1e
更新日期:2004-02-01 00:00:00
abstract::The present review discusses drugs and counter ions suitable for ion pair transport (IPT). Ion pairing is shown to effectively increase the lipophilicity and transport rate of polar drugs across lipid membranes. The proposed mechanisms of IPT are discussed in detail. A marked change in drug properties upon ion pair fo...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1023/a:1015963128124
更新日期:1989-09-01 00:00:00
abstract::Human serum albumin (HSA) was encapsulated in a 50:50 copolymer of DL-lactide/glycolide in the form of microspheres. These microspheres were used as a model formulation to study the feasibility of controlling the release of large proteins over a 20- to 30-day period. We show that HSA can be successfully incorporated i...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015948829632
更新日期:1990-11-01 00:00:00
abstract::The delivery of therapeutic nucleic acids to neurons has the potential to treat neurological disease and spinal cord injury. While select viral vectors have shown promise as gene carriers to neurons, their potential as therapeutic agents is limited by their toxicity and immunogenicity, their broad tropism, and the cos...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-007-9439-5
更新日期:2008-05-01 00:00:00
abstract:PURPOSE:The major goal of this study was to compare the relative utility of the Hanson Microette and the Van Kel apparatus, two fully automated devices, as in vitro release tests (IVRT) for semisolids. We attempted to develop methodology that can be used to discriminate formulation changes, and to evaluate the precisio...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012256923340
更新日期:2001-10-01 00:00:00
abstract::Diltiazem (DTZ) is a calcium channel blocker widely used in the treatment of angina and hypertension. DTZ undergoes extensive metabolism yielding several metabolites, some of which are active like N-desmethyldiltiazem (MA), desacetyldiltiazem (M1) and N-desmethyl,desacetyldiltiazem (M2). Due to the nature of its biotr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016226601988
更新日期:1995-04-01 00:00:00
abstract:PURPOSE:The structure-function relationship and mechanism of polycations as gene carriers have attracted considerable research interest in recent years. The present study was to investigate the relationship between polycation chain length and transfection efficiency (RCL-TE), and the corresponding mechanism by O-methyl...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1211-4
更新日期:2014-04-01 00:00:00
abstract::Moisture sorption characteristics and the effect of moisture content on the compression properties of two dextrose-based directly compressible diluents, namely, Emdex (diluent A) and Sweetrex (diluent B) were studied. Both diluents sorbed moisture rapidly at relative humidities greater than 60%. For both the diluents,...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015889414533
更新日期:1991-03-01 00:00:00
abstract:PURPOSE:Locoregional recurrence is the most common complication after adenocarcinoma resection in the colon, despite adjuvant chemotherapy. Therapy efficacy could be improved if designed to target malignant cells by incorporating specific recognition factors in the drugs or the drug vehicles. The aim of this study was ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9330-4
更新日期:2008-02-01 00:00:00
abstract:PURPOSE:To identify the mechanism behind the unexpected bio-performance of two amorphous solid dispersions: BMS-A/PVP-VA and BMS-A/HPMC-AS. METHODS:Solubility of crystalline BMS-A in PVP-VA and HPMC-AS was measured by DSC. Drug-polymer interaction parameters were obtained by Flory-Huggins model fitting. Drug dissoluti...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0695-7
更新日期:2012-10-01 00:00:00
abstract:PURPOSE:The objective of this study was to develop and characterize long-circulating, biodegradable, and biocompatible nanoparticulate formulation as an intracellular delivery vehicle. METHODS:Poly(ethylene glycol) (PEG)-modified gelatin was synthesized by reacting Type-B gelatin with PEG-epoxide. The nanoparticles, p...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016486910719
更新日期:2002-07-01 00:00:00
abstract:PURPOSE:To evaluate and classify the hydrolases of the primate lung. METHODS:Homologous series of aromatic, aliphatic, and choline ester substrates were assayed with the pH-stat method to obtain the Michaelis-Menten kinetic constants, Vmax and K(m), for the enzymes in pulmonary alveolar tissue with esterase activity. ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012004911942
更新日期:1997-02-01 00:00:00
abstract::An oral formulation of controlled-release isosorbide-5-nitrate pellets has been used to investigate the location of pellets in the gastrointestinal (GI) tract and, in parallel, to measure the drug absorption from these locations. Using the method of gamma scintigraphy the transit times and spreading of pellets in the ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016423404636
更新日期:1987-12-01 00:00:00
abstract::The relationship between pKa and skin irritation in man is studied for a homologous series of benzoic acid derivatives, which permeate through human skin at comparable rates (15-88 micrograms/cm2/hr). Skin irritation and pKa are correlated for pKa less than or equal to 4. Laser Doppler velocimetric assessment of skin ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015931105660
更新日期:1988-10-01 00:00:00
abstract:PURPOSE:We have already demonstrated that the HMG-CoA reductase inhibitor, pravastatin is actively taken up by isolated rat hepatocytes via a multispecific anion transporter (Yamazaki et al., Am. J. Physiol. 264, G36-44, (1993)). We further attempted the quantitative evaluation of this uptake in different experimental ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016226024587
更新日期:1995-11-01 00:00:00
abstract:PURPOSE:Scutellarin, a flavonoid derived from the plant Erigeron breviscapus, is currently widely used to treat cerebrovascular diseases, liver-related diseases, and hyperlipidemia in china and other East Asian countries. This study was to investigate the effect of scutellarin on the uptake of rosuvastatin in HEK293T c...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02950-5
更新日期:2020-10-29 00:00:00
abstract:PURPOSE:To compare the adjuvanticity of polymeric particles (new-generation adjuvant) and alum (the traditional and FDA-approved adjuvant) for H5N1 influenza split vaccine, and to investigate respective action mode. METHODS:Vaccine formulations were prepared by incubating lyophilized poly(lactic acid) (PLA) microparti...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1224-z
更新日期:2014-04-01 00:00:00
abstract:PURPOSE:To characterize temporal exposure and elimination of 5 gold/dendrimer composite nanodevices (CNDs) (5 nm positive, negative, and neutral, 11 nm negative, 22 nm positive) in mice using a physiologically based mathematical model. METHODS:400 ug of CNDs is injected intravenously to mice bearing melanoma cell line...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0784-7
更新日期:2012-09-01 00:00:00
abstract::We studied the effects of two verapamil analogs, anipamil and ronipamil, in traumatic shock. Noble-Collip drum trauma produced a shock state characterized by an eight-fold increase in plasma cathepsin D activity, a 13-fold increase in the rate of plasma myocardial depressant factor (MDF) accumulation, and a survival t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016363316777
更新日期:1985-05-01 00:00:00
abstract:PURPOSE:To provide a systematic biophysical approach towards a better understanding of impact of conjugation chemistry on higher order structure and physical stability of an antibody drug conjugate (ADC). METHODS:ADC was prepared using thiol-maleimide chemistry. Physical stabilities of ADC and its parent IgG1 mAb were...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1274-2
更新日期:2014-07-01 00:00:00
abstract:PURPOSE:To assess the effects of co-delivering osteoinductive DNA and/or small interfering RNA in directing the osteogenic differentiation of human adipose-derived stem cells (hADSCs) using a combinatorial, non-viral gene delivery approach. METHODS:hADSCs were transfected using combinations of the following genes: BMP...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0406-9
更新日期:2011-06-01 00:00:00