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排序方式: 共有306条查询结果,搜索用时 218 毫秒
1.
Bhavana Pothuri Allison L. Brodsky Joseph A. Sparano Stephanie V. Blank Mimi Kim Dawn L. Hershman Amy Tiersten Brian F. Kiesel Jan H. Beumer Leonard Liebes Franco Muggia 《Cancer chemotherapy and pharmacology》2020,85(4):741-751
Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1–14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID. The RP2D is 200 mg veliparib BID on days 1–14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy. 相似文献
2.
R. R. Beumer M. C. te Giffel E. Spoorenberg F. M. Rombouts 《Epidemiology and infection》1996,117(3):437-442
Using a direct isolation method Listeria spp. were detected in 101 (47.4%) of 213 houses investigated. L. monocytogenes was present in 45 houses (21.1%). Listeria spp. occurred at all sampling sites. Dish-cloths (37%) and surface samples round the drain in the bathroom (27.2%) were most frequently contaminated. Highest numbers (c. 10(4) c.f.u./object) were found in dish-cloths and washing-up brushes. Lower levels (up to 10(3) c.f.u./object) were obtained from kitchen sinks, refrigerator vegetable compartment samples and tooth brushes. In total, 132 isolations of Listeria spp. were made from 871 samples. L. innocua (53%) and L. monocytogenes (41%) were the predominant species in the positive samples. Other Listeria spp. were found in only 6% of the positive samples. 相似文献
3.
S Lewis S Avera M Engleman J Beumer 《The International journal of oral & maxillofacial implants》1989,4(2):147-152
Improper implant angulation is one of the most difficult problems to overcome in the fabrication of implant-supported and implant-retained restorations. Several techniques using the "UCLA" abutment have been developed to solve these problems. The creation of large screw-access holes for moderate angulation and the fabrication of telescopic copings and overlay castings for severe angulation problems are discussed. 相似文献
4.
M. R. Visser I. M. Hoepelman H. Beumer M. Rozenberg-Arska J. Verhoef 《European journal of clinical microbiology & infectious diseases》1989,8(12):1061-1064
The in vitro antimicrobial activity of the new carbapenem meropenem (SM-7338) was determined by an agar dilution method in comparison with imipenem, ticarcillin/calvulanic acid, ceftazidime and the fourth-generation cephalosporin cefepime (BMY 28142). Meropenem showed superior activity againstEnterobacteriaceae (MIC900.06 mg/l) and against non-fermentative gram-negative rods, with the exception ofXanthomonas maltophilia. Meropenem had excellent activity against beta-lactamase-producingHaemophilus influenzae andNeisseria gonorrhoeae, and against theBacteroides fragilis group. Imipenem was slightly more active then meropenem against gram-positive cocci especiallyEnterococcus faecalis. 相似文献
5.
Summary In 20 patients with an acute exacerbation of chronic respiratory tract infection the effectiveness of oral erythromicin succinate 3×500 mg daily has been tested. The duration of treatment was 10 days in all cases. The criteria of success, in addition to the clinical findings, were the results of bacteriological investigations and assessment of the appearance of the sputum. In all patients sputum and serum concentrations or erythromicin were determined. All pathogens isolated from the sputum of the patients were erythromicin-sensitive. One instance of development of resistance was observed. The drug was well tolerated. 相似文献
6.
7.
Cancer Chemotherapy and Pharmacology - 相似文献
8.
9.
Guido van Amerongen Kawita Kanhai Anne Catrien Baakman Jules Heuberger Erica Klaassen Tim L. Beumer Rob L.M. Strijers Joep Killestein Joop van Gerven Adam Cohen Geert Jan Groeneveld 《Clinical therapeutics》2018,40(9):1467-1482
Purpose
The aim of the present study was to evaluate the efficacy of an oral formulation of Δ9-tetrahydrocannabinol (ECP002A) in patients with progressive multiple sclerosis (MS).Methods
This accelerated proof-of-concept study consisted of 2 phases: a crossover challenge (dose-finding) phase and a 4-week, parallel, randomized, placebo-controlled treatment phase. Twenty-four patients with progressive MS and moderate spasticity were enrolled. During the treatment phase, biomarkers for efficacy and secondary pharmacodynamic effects were measured at baseline and after 2 and 4 weeks of treatment. Serum samples were collected to determine pharmacokinetic properties and perform population modeling. Safety and tolerability profiles were assessed based on adverse events and safety measurements.Findings
Pain was significantly reduced when measured directly after administration of ECP002A in the clinic but not when measured in a daily diary. A similar pattern was observed in subjective muscle spasticity. Other clinical outcomes were not significantly different between active treatment and placebo. Cognitive testing indicated that there was no decline in cognition after 2 or 4 weeks of treatment attributable to ECP002A compared with placebo.ImplicationsThis study specifically underlines the added value of thorough investigation of pharmacokinetic and pharmacodynamic associations in the target population. Despite the complex interplay of psychoactive effects and analgesia, the current oral formulation of Δ9-tetrahydrocannabinol may play a role in the treatment of spasticity and pain associated with MS because it was well tolerated and had a stable pharmacokinetic profile. 相似文献10.
Jan H Beumer Venkateswaran C Pillai Robert A Parise Susan M Christner Brian F Kiesel Michelle A Rudek Raman Venkataramanan 《British journal of clinical pharmacology》2015,80(5):1097-1108