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Tumour Vasculature (tumour + vasculature)

Distribution by Scientific Domains

Medical Sciences	71%

Selected Abstracts

SELECTIVE TARGETING OF THE TUMOUR VASCULATURE,

ANZ JOURNAL OF SURGERY, Issue 11 2008
Lie S. Chan
Selective targeting of the tumour vasculature in the treatment of solid organ malignancies is an alternative to conventional chemotherapy treatment. As the tumour progressively increases in size, angiogenesis or the formation of new vasculature is essential to maintain the tumour's continual growth and survival. Therefore disrupting this angiogenic process or targeting the neovasculature can potentially hinder or prevent further tumour expansion. Many anti angiogenic agents have been investigated with many currently in clinical trials and exhibiting varied results. Vascular disrupting agents such as the Combretastatins and OXi 4503 have shown promising preclinical results and are currently being examined in clinical trials. [source]

Osteoprotegerin (OPG),a potential new role in the regulation of endothelialcell phenotype and tumour angiogenesis?

INTERNATIONAL JOURNAL OF CANCER, Issue 8 2006
Simon S. Cross
Abstract The progression of cancer depends on the establishment of a tumour blood supply, and therefore tumour angiogenesis has been identified as a major target for new anticancer agents. Recent reports have suggested that osteoprotegerin (OPG) is involved in the control of endothelial cell survival through the inhibition of the activity of tumour necrosis factor- (TNF) related apoptosis-inducing ligand (TRAIL). The role of OPG in human tumour development and angiogenesis is currently unknown. In the present study we demonstrate the ability of OPG to support endothelial cell survival, as well as the formation of cord-like structures in vitro using a matrigel tubule formation assay. Investigation of various human cancers demonstrated endothelial OPG expression in 59% of malignant tumours (n = 512), but in contrast, OPG was absent in endothelial cells associated with benign tumours and normal tissues (n = 178). In a series of 400 breast tumours, endothelial OPG expression was associated with high tumour grade and certain histological types. Our data show a clear separation in endothelial OPG expression between malignant tumours and nonmalignant tissues, supporting a potential biological role for this molecule in the development and/or maintenance of the tumour vasculature. This is the first study to report the proangiogenic effects of OPG in vitro, as well as correlating expression of OPG by tumour endothelial cells with clinicopathological data in human tumours. © 2005 Wiley-Liss, Inc. [source]

Evaluation of the anti-vascular effects of combretastatin in rodent tumours by dynamic contrast enhanced MRI

NMR IN BIOMEDICINE, Issue 2 2002
Ross J. Maxwell
The anti-vascular effects of the tubulin binding agent, disodium combretastatin A-4 3- O -phosphate (CA-4-P), have been investigated in the rat P22 carcinosarcoma by measurements of radiolabelled iodoantipyrine uptake and dynamic contrast-enhanced MRI. The iodoantipyrine estimates of absolute tumour blood flow showed a reduction from 0.35 to 0.04,ml g,1 min,1 6,h after 10,mg kg,1 CA-4-P and to <0.01,ml g,1 min,1 after 100,mg kg,1. Tumour blood flow recovered to control values 24,h after 10,mg kg,1 CA-4-P, but there was no recovery by 24,h after the higher dose. Dynamic contrast-enhanced MR images were obtained at 4.7 T, following injection of 0.1,mmol kg,1 Gd-DTPA and analysed assuming a model arterial input function. A parameter, Ktrans, which is related to blood flow rate and permeability of the tumour vasculature to Gd-DTPA, was calculated from the uptake data. Ktrans showed a reduction from 0.34 to 0.11 min,1 6,h after 10,mg kg,1 CA-4-P and to 0.07 min,1 after 100,mg kg,1. Although the magnitude of changes in Ktrans was smaller than that in tumour blood flow, the time course and dose-dependency patterns were very similar. The apparent extravascular extracellular volume fraction, ,e, showed a four-fold reduction 6,h after 100,mg kg,1 CA-4-P, possibly associated with vascular shutdown within large regions of the tumour. These results suggest that Ktrans values for Gd-DTPA uptake into tumours could be a useful non-invasive indicator of blood flow changes induced by anti-vascular agents such as combretastatin. Copyright © 2002 John Wiley & Sons, Ltd. [source]

In vivo efficacy of HSV-TK transcriptionally targeted to the tumour vasculature is augmented by combination with cytotoxic chemotherapy

THE JOURNAL OF GENE MEDICINE, Issue 3 2005
Georgia Mavria
Abstract Background Retroviral vectors are suitable for targeting endothelial cells in the tumour neovasculature because of their intrinsic selectivity for proliferating cells. Previously, we inserted regulatory elements of the endothelial-specific prepro-endothelin-1 (ppET1) promoter in retroviral vectors to generate high-titre, replication-defective recombinant retroviruses that restricted gene expression to the vascular compartment of tumours. Methods A retroviral vector was generated in which expression of herpes simplex virus thymidine kinase (HSV-TK) was transcriptionally restricted to endothelial cells, under the control of a hybrid ppET-1 LTR. Xenograft tumour models were used to determine the efficacy of targeting HSV-TK to the tumour vasculature. Subsequently, vascular-targeted gene therapy was combined with chemotherapeutic agents. Results Breast or colorectal xenograft tumour growth was reduced and survival was increased in response to ganciclovir treatment. Treatment resulted in widespread vascular disruption and tumour cell apoptosis. In colorectal tumours, combination with irinotecan, a cytotoxic drug used to treat colorectal cancer, significantly increased survival compared to drug alone. No beneficial effect on survival was observed when combined with cisplatin, a cytotoxic drug not in clinical use for this tumour type. On the basis of their relative efficacies in vitro against tumour and endothelial cells, co-operativity with irinotecan likely derives from additionally targeting the peripheral tumour cells that survive the anti-vascular treatment. Conclusions We show that the ppET1-targeted vector is efficacious for therapeutic gene expression in vivo, validating a strategy targeted to tumour vasculature, and demonstrate that vascular targeting combined with appropriate chemotherapy is more effective than either therapy alone. Copyright © 2004 John Wiley & Sons, Ltd. [source]

SELECTIVE TARGETING OF THE TUMOUR VASCULATURE,

Vehicles for oligonucleotide delivery to tumours

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2002
Crispin R. Dass
The vasculature of a tumour provides the most effective route by which neoplastic cells may be reached and eradicated by drugs. The fact that a tumour's vasculature is relatively more permeable than healthy host tissue should enable selective delivery of drugs to tumour tissue. Such delivery is relevant to carrier-mediated delivery of genetic medicine to tumours. This review discusses the potential of delivering therapeutic oligonucleotides (ONs) to tumours using cationic liposomes and cyclodextrins (CyDs), and the major hindrances posed by the tumour itself on such delivery. Cationic liposomes are generally 100,200 nm in diameter, whereas CyDs typically span 1.5 nm across. Cationic liposomes have been used for the introduction of nucleic acids into mammalian cells for more than a decade. CyD molecules are routinely used as agents that engender cholesterol efflux from lipid-laden cells, thus having an efficacious potential in the management of atherosclerosis. A recent trend is to employ these oligosaccharide molecules for delivering nucleic acids in cells both in-vitro and in-vivo. Comparisons are made with other ON delivery agents, such as porphyrin derivatives (< 1 nm), branched chain dendrimers (, 10 nm), polyethylenimine polymers (, 10 nm), nanoparticles (20,1000 nm) and microspheres (> 1 ,m), in the context of delivery to solid tumours. A discourse on how the chemical and physical properties of these carriers may affect the uptake of ONs into cells, particularly in-vivo, forms a major basis of this review. [source]