Pharmacokinetics of methotrexate in solid tumors

Jain, Rakesh K.; Wei, James Cheng‐Chung; Gullino, Pietro M.

doi:10.1007/bf01059737

Cited by 31 publications

(13 citation statements)

References 9 publications

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“…(For details, see [46] [56,102]). Although a tumor preparation with a single artery and a single vein is available [111][112][113], this method has not been used for permeability studies in tumors.…”

Section: Macroscopic Methodsmentioning

confidence: 99%

Transport of molecules across tumor vasculature

1987

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The vascular-extravascular exchange of fluid and solute molecules in a tissue is determined by three transport parameters (vascular permeability, P, hydraulic conductivity, Lp, and reflection coefficient, sigma); the surface area for exchange, A; and the transluminal concentration and pressure gradients. The transport parameters and the exchange area for a given molecule are governed by the structure of the vessel wall. In general, tumor vessels have wide interendothelial junctions; large number of fenestrae and transendothelial channels formed by vesicles; and discontinuous or absent basement membrane. While these factors favor movement of molecules across tumor vessels, high interstitial pressure and low microvascular pressure may retard extravasation of molecules and cells, especially in large tumors. These characteristics of the transvascular transport have significant implications in tumor growth, metastasis, detection and treatment.

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Section: Macroscopic Methodsmentioning

confidence: 99%

Transport of molecules across tumor vasculature

1987

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“…In the first approach, we simulated the tumor vasculature in vitro, by incubating the human umbilical vein endothelial cells (HUVECs) in the tumor interstitial fluid collected using a micropore chamber [6,33,56,118]. Using targeted sampling fluorometry (Fig.…”

Section: Transport Of Cellsmentioning

confidence: 99%

Delivery of molecular and cellular medicine to solid tumors

Jain

2012

Advanced Drug Delivery Reviews

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To reach cancer cells in a tumor, a blood-borne therapeutic molecule or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, and finally migrate through the interstitium. Unfortunately, tumors often develop in ways that hinder each of these steps. Our research goals are to analyze each of these steps experimentally and theoretically, and then integrate the resulting information in a unified theoretical framework. This paradigm of analysis and synthesis has allowed us to obtain a better understanding of physiological barriers in solid tumors, and to develop novel strategies to exploit and/or to overcome these barriers for improved cancer detection and treatment.

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“…Other in vestigators have previously used such micro pore chambers for studying metabolic prod ucts of sugars [19], pH [20], and methotrex ate accumulation [24] in rat tumors. This appears to be the first report on the use of micropore chambers for studying a number of human tumors grown as xenografts in althymic mice.…”

Section: Discussionmentioning

confidence: 99%

Correlation of Catabolism and Antigen Shedding with Monoclonal Antibody Uptake by Human Colon and Lung Tumor Xenografts

Shah

1991

Tumor Biol

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Catabolism of B6.2 and B72.3 monoclonal antibodies by human colon (LS174T) and lung (A549) tumor xenografts appears to be a variable and complex process. ¹²⁵I-B72.3 and ¹²⁵I-B6.2 bound to LS174T cells in vitro and localized in tumors in athymic mice. ¹²⁵I-B6.2 bound to A549 cells in vitro, but did not localize in tumors. To understand these differences, tumors were grown around subcutaneously implanted micropore chambers and tumor fluid was analyzed for the presence of shed tumor antigen or functional antibody following intravenous injection. Up to two orders of magnitude lower functional B6.2 was detected in the A549 tumor fluid than in the LS174T tumor fluid. Also, A549 fluid almost totally (82–94%) inhibited binding of ¹²⁵I-B6.2 to target cells in vitro due to free B6.2 antigen present in the chamber fluid. The micropore chambers utilized in this study have the potential for expanding our understanding of the way antibodies are metabolized in various types of tumors. Utility of an antibody in vivo cannot be entirely predicted from in vitro binding studies given that tumor related factors such as antibody transport, antibody catabolism and shed antigen may influence localization of antibodies in tumors. Monoclonal antibodies against nonshed antigens may prove to be more appropriate for cancer imaging and therapy.

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Pharmacokinetics of methotrexate in solid tumors

Cited by 31 publications

References 9 publications

Transport of molecules across tumor vasculature

Transport of molecules across tumor vasculature

Delivery of molecular and cellular medicine to solid tumors

Correlation of Catabolism and Antigen Shedding with Monoclonal Antibody Uptake by Human Colon and Lung Tumor Xenografts

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