Decrease in tumor apparent permeability-surface area product to a MRI macromolecular contrast medium following angiogenesis inhibition with correlations to cytotoxic drug accumulation.

BACKGROUND: New strategies for cancer therapy include the combination of angiogenesis inhibitors with cytotoxins. However, angiogenesis inhibitors may alter tumor microvessel structure and transendothelial permeability thereby reducing tumoral delivery of cytotoxic agents. The aim of this study was to estimate quantitatively the apparent permeability-surface area product (K(PS)) in tumors to a macromolecular contrast medium (MMCM), to follow changes in K(PS) induced by antibodies to vascular endothelial growth factor (anti-VEGF), and to correlate the findings with tumor accumulation of cisplatin, a highly protein-bound cytotoxin, and 5-fluorouracil (5-FU), a small unbound cytotoxin. METHODS: Dynamic MRI enhanced with a MMCM (albumin-(Gd-DTPA)(30)) was analyzed using a two-compartment tumor tissue model (plasma and interstitial water) to quantitatively estimate K(PS). These estimates of K(PS) were correlated with cytotoxic drug accumulations in the tumors. RESULTS: Anti-VEGF treatment reduced K(PS) to MMCM in tumor tissue from 0.013 mL h(-1) cm(-3) (n = 9) at baseline to 0.003 mL h(-1) cm(-3) (n = 9) 24 h later (p <.05). The K(PS) values correlated significantly (r(2) =.78; p <.0001) with the tumor cisplatin accumulation. No correlation (r(2) =.001; p =.89) was found between K(PS) and tumor accumulation of the substantially smaller 5-FU molecule. CONCLUSIONS: MMCM-enhanced MRI can be used to detect and estimate changes in K(PS) to this contrast agent following a single dose of anti-VEGF antibody. The decline in K(PS) induced by this inhibitor of angiogenesis is associated with reduced tumor concentration of a protein-bound cytotoxin, similar in molecular weight to the contrast agent. MRI assays of microvascular status as performed here may be useful to clinically monitor responses to anti-angiogenesis drugs and to optimize the choice and timing of cytotoxic drug administration.

A histological and histochemical study of the male reproductive system of artemia (Crustacea, Branchiopoda).

The male reproductive system of Artemia was studied by routine histological and histochemical techniques to demonstrate the general histology and distribution of proteins, carbohydrates, lipids, and alkaline and acid phosphatases. The System Consists Of Paired Testes, Vasa Deferentia, Accessory Glands, And Penes. The Testes Contain Germ Cells And Supporting Cells Throughout Their Entire Length. The Former Cells Are Located In Clusters And Undergo A Spermatogenic Maturation Which Is Similar To That Described For OtherAnimals. The Supporting Cells Seem Implicated In The Nourishment Of The Germ Cells. The Vas Deferens, Which Consists Of Secretory Epithelium Surrounded By Circular And Longitudinal Muscles, Secretes The Seminal Fluid, Containing A Neutral Mucopolysaccharide Or Mucoprotein, And Stores The Mature Sperm. The Accessory Gland Consists Of Approximately 20 Pairs Of Gland Cells, Each Pair Drained By A Neck Cell And Duct Cell Into The Collecting Duct. The Glandular Secretion, Mainly A Neutral Mucopolysaccharide Or Mucoprotein, Might Function As A Lubricant, A Copulatory Plug, Or An "Activator Substance" For The Sperm Or For Fertilization. Each Penis Consists Of A Non-Eversible Part And An Eversible Part Which Is A Tortuous Muscular Tube That Connects The Vas Deferens To The Outside.