M. Guillaume Wientjes

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Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA. The high mortality rate is partly due to lack of effective treatments. This review summarizes the pathobiology and current treatment options for pancreatic cancer. Moreover, the review discusses the opportunities of developing novel therapies for pancreatic cancer provided by(More)
RNA interference is a naturally occurring endogenous regulatory process where short double-stranded RNA causes sequence-specific posttranscriptional gene silencing. Small interference RNA (siRNA) represents a promising therapeutic strategy. Clinical evaluations of siRNA therapeutics in locoregional treatment settings began in 2004. Systemic siRNA therapy is(More)
Paclitaxel is a substrate of the mdr1 P-glycoprotein (Pgp). The objective of the present study was to determine the kinetics of the Pgp-mediated efflux and its contribution to the overall efflux of paclitaxel at the clinically achievable concentration range of 1 to 1500 nM. Human breast carcinoma BC19 cells that were derived from MCF7 cells by mdr1(More)
The goal of the present report is to compare several published methods of analyzing drug-drug interaction data. The compared methods are the curve-shift analysis, isobologram, combination index, and universal surface response analysis, and the comparison was based on analysis of published cytotoxicity data of combinations of two anti-folate agents. Major(More)
Isobologram and combination index (CI) analyses are the two most popular methods for evaluating drug interactions in combination cancer chemotherapy. As the commonly used CI-based software program uses linear regression, our first objective was to evaluate the effects of logarithmic data transformation on data analysis and conclusions. Monte-Carlo(More)
We have shown that high epithelial cell density is a major barrier to the distribution of protein-bound drugs in solid tumors, and tumor priming (expansion of interstitial space using an apoptosis-inducing pretreatment) can promote drug delivery. This study evaluated the optimal conditions of paclitaxel tumor priming (time window, particle size) and its(More)
The limited penetration of paclitaxel into solid tumors may limit its therapeutic efficacy. We recently showed a correlation between an increase in interstitial space and an enhancement of drug delivery in solid tumors. The present study evaluated whether this observation can be used to develop a treatment strategy, where an apoptosis-inducing pretreatment(More)
Purpose. The purpose of this review is to provide an overview of the principles of and barriers to drug transport and delivery to solid tumors. Methods. This review consists of four parts. Part I provides an overview of the differences in the vasculature in normal and tumor tissues, and the relationship between tumor vasculature and drug transport. Part II(More)
BACKGROUND Intravesical chemotherapy (i.e., placement of the drug directly in the bladder) with mitomycin C is beneficial for patients with superficial bladder cancer who are at high risk of recurrence, but standard therapy is empirically based and patient response rates have been variable, in part because of inadequate drug delivery. We carried out a(More)
The intracellular pharmacokinetics of paclitaxel is closely related to its pharmacodynamics. Although drug transport across the cell membrane and extracellular and intracellular drug binding have been shown to affect intracellular drug accumulation, their quantitative relationship is unknown. This study was designed to establish a mathematical model for(More)