JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kuh, H.-J.
Right arrow Articles by Au, J. L.-S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kuh, H.-J.
Right arrow Articles by Au, J. L.-S.

Vol. 290, Issue 2, 871-880, August 1999

Determinants of Paclitaxel Penetration and Accumulation in Human Solid Tumor1

Hyo-Jeong Kuh2, Seong H. Jang, M. Guillaume Wientjes, Jean R. Weaver and Jessie L.-S. Au

College of Pharmacy, The Ohio State University, Columbus, Ohio

The present study examined the determinants of the penetration and accumulation of [3H]paclitaxel (12-12,000 nM) in three-dimensional histocultures of patient tumors and of a human xenograft tumor in mice. The results showed 1) significant and saturable drug accumulation in tumors, 2) extensive drug retention in tumors, and 3) a slower penetration but a more extensive accumulation in the xenograft tumor compared with patient tumors. Drug penetration was not rate-limited by drug diffusion from medium through the matrix supporting the histocultures. The difference in the expression of the mdr1 P-glycoprotein did not fully account for the difference in the drug accumulation in xenograft and patient tumors. Autoradiography and imaging were used to evaluate the spatial relationship between tumor architecture, tumor cell distribution, and drug distribution as a function of time and initial drug concentration in culture medium. The tumor cell density and the kinetics of drug-induced apoptosis were also evaluated. The results indicate that a high tumor cell density is a barrier to paclitaxel penetration and that the apoptotic effect of paclitaxel enhances its penetration in solid tumor. These factors are responsible for the time- and concentration-dependent drug penetration rate, with drug penetration confined to the periphery until apoptosis and reduction of epithelial cell density occurred at 24 h, after which time paclitaxel penetrated the inner parts of the tumor.

0022-3565/99/2902-0871$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
Z. Lu, M. Tsai, D. Lu, J. Wang, M. G. Wientjes, and J. L.-S. Au
Tumor-Penetrating Microparticles for Intraperitoneal Therapy of Ovarian Cancer
J. Pharmacol. Exp. Ther., December 1, 2008; 327(3): 673 - 682.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
E. deBree, H. Rosing, D. Filis, J. Romanos, M. Melisssourgaki, M. Daskalakis, M. Pilatou, E. Sanidas, P. Taflampas, K. Kalbakis, et al.
Cytoreductive Surgery and Intraoperative Hyperthermic Intraperitoneal Chemotherapy with Paclitaxel: A Clinical and Pharmacokinetic Study
Ann. Surg. Oncol., April 1, 2008; 15(4): 1183 - 1192.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
V. Vassileva, C. J. Allen, and M. Piquette-Miller
Effects of sustained and intermittent paclitaxel therapy on tumor repopulation in ovarian cancer
Mol. Cancer Ther., March 1, 2008; 7(3): 630 - 637.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
J. C. Friedland, J. N. Lakins, M. G. Kazanietz, J. Chernoff, D. Boettiger, and V. M. Weaver
{alpha}6beta4 integrin activates Rac-dependent p21-activated kinase 1 to drive NF-{kappa}B-dependent resistance to apoptosis in 3D mammary acini
J. Cell Sci., October 15, 2007; 120(20): 3700 - 3712.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
O. Tredan, C. M. Galmarini, K. Patel, and I. F. Tannock
Drug Resistance and the Solid Tumor Microenvironment
J Natl Cancer Inst, October 3, 2007; 99(19): 1441 - 1454.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
T. Yan, L Welch, D Black, and P. Sugarbaker
A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma
Ann. Onc., May 1, 2007; 18(5): 827 - 834.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. H. Kyle, L. A. Huxham, D. M. Yeoman, and A. I. Minchinton
Limited Tissue Penetration of Taxanes: A Mechanism for Resistance in Solid Tumors
Clin. Cancer Res., May 1, 2007; 13(9): 2804 - 2810.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
T. D. Yan, G. Edwards, R. Alderman, C. E. Marquardt, and P. H. Sugarbaker
Morbidity and Mortality Assessment of Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma--A Prospective Study of 70 Consecutive Cases
Ann. Surg. Oncol., February 1, 2007; 14(2): 515 - 525.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Grantab, S. Sivananthan, and I. F. Tannock
The Penetration of Anticancer Drugs through Tumor Tissue as a Function of Cellular Adhesion and Packing Density of Tumor Cells
Cancer Res., January 15, 2006; 66(2): 1033 - 1039.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
P. H. Sugarbaker, J. T. Mora, P. Carmignani, O. A. Stuart, and D. Yoo
Update on Chemotherapeutic Agents Utilized for Perioperative Intraperitoneal Chemotherapy
Oncologist, February 1, 2005; 10(2): 112 - 122.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
S. Sharma, D. White, A. R. Imondi, M. E. Placke, D. M. Vail, and M. G. Kris
Development of Inhalational Agents for Oncologic Use
J. Clin. Oncol., March 15, 2001; 19(6): 1839 - 1847.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. H. Jang, M. G. Wientjes, and J. L.-S. Au
Enhancement of Paclitaxel Delivery to Solid Tumors by Apoptosis-Inducing Pretreatment: Effect of Treatment Schedule
J. Pharmacol. Exp. Ther., March 1, 2001; 296(3): 1035 - 1042.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
H.-J. Kuh, S. H. Jang, M. G. Wientjes, and J. L.-S. Au
Computational Model of Intracellular Pharmacokinetics of Paclitaxel
J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 761 - 770.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.