Identification of vascular surface proteins by in vivo biotinylation: a method sufficiently sensitive to detect changes in rat liver 2 weeks after partial hepatectomy.

We have developed a methodology to selectively isolate and identify proteins associated with the luminal surface of blood vessels using in vivo biotinylation, streptavidin-affinity chromatography, and SDS-PAGE/LC-MS/MS. This had sufficient sensitivity to identify 32 proteins with changed expression in rat livers at 2 weeks or 5 weeks after partial hepatectomy, well after the 7 day tissue remodeling period. This method could be adapted to study other angiogenic tissues including tumors.

Enhancement of cisplatin efficacy by thalidomide in a 9L rat gliosarcoma model.

With the aim of improving the treatment of glioblastoma multiforme, we investigated the potential of thalidomide to enhance the effectiveness of cisplatin chemotherapy in a rat glioma model. Female F344 rats were implanted with 9L gliosarcoma tumors either intracranially or subcutaneously and treated with 1 mg/kg cisplatin injected i.p.

Enantioselectivity of thalidomide serum and tissue concentrations in a rat glioma model and effects of combination treatment with cisplatin and BCNU.

Thalidomide is currently under evaluation as an anti-angiogenic agent in cancer treatment, alone and in combination with cytotoxic agents. Thalidomide is a racemate with known pharmacologic and pharmacokinetic enantioselectivity. In a previous study with thalidomide combination chemotherapy, we found evidence of anti-tumour synergy.

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells.

Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines. Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance.

Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing.

Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation, and has more recently been shown to be a potent anti-inflammatory mediator. Using cultured human cells, we show here that APC up-regulates the angiogenic promoters matrix metalloproteinase-2 in skin fibroblasts and umbilical vein endothelial cells, vascular endothelial growth factor in keratinocytes and fibroblasts, and monocyte chemoattractant protein-1 in fibroblasts. In the chick embryo chorioallantoic membrane assay, APC promoted the granulation/remodeling phases of wound healing by markedly stimulating angiogenesis as well as promoting reepithelialization.

Changes in gene expression associated with stable drug and radiation resistance in small cell lung cancer cells are similar to those caused by a single X-ray dose.

Small cell lung cancer (SCLC) initially responds well to chemotherapy and fractionated radiotherapy, but resistance to these treatments eventually develops in the vast majority of cases. To understand how resistance develops in the H69 SCLC cell line, we compared the changes in gene expression associated with 37.5 Gy fractionated X-ray treatment that produced the stable radiation- and drug-resistant H69/R38 cell subline to the changes associated with a single 4- or 8-Gy X-ray treatment.

Cellular models of drug- and radiation-resistant small cell lung cancer.

Background: The H69-EPR, H69-CP, H69-VP and H69/R38 resistant sublines of the classic small cell lung cancer (SCLC) line have proven useful in studies of resistance and its circumvention with paclitaxel.

Materials And Methods: The suppressor/oncogene profile of these sublines determined by Western and Northern blot was compared to the variant H82 SCLC cell profile. Two-dimensional electrophoresis/mass spectrometry was used to determine the effect of paclitaxel on protein expression.

Modulation of drug and radiation resistance in small cell lung cancer cells by paclitaxel.

Small cell lung cancer (SCLC) responds to treatment with cisplatin and etoposide, but relapse is rapid and survival rates are low. Our aims were to determine the mechanisms of resistance and the potential for paclitaxel (Taxol) to overcome any drug or radiation resistance. To mimic clinical treatment, H69 SCLC cells, representative of the classic form of the disease, and H82 cells, with the phenotype of the more resistant variant disease, were treated intermittently with 100 ng/ml cisplatin or 500 ng/ml etoposide (approximate IC50 drug doses) to produce stable sublines.

The use of Tris-lipidation to modify drug cytotoxicity in multidrug resistant cells expressing P-glycoprotein or MRP1.

1. Increasing the lipophilicity is a strategy often used to improve a compound's cellular uptake and retention but this may also convert it into a substrate for an ATP-dependent transporter such as P-glycoprotein or the multidrug resistance-associated protein (MRP1), which are involved in cellular efflux of drugs. Tris-Lipidation of compounds is a convenient way of modifying drug lipophilicity and generating an array of derivatives with diverse properties.

Fractionated irradiation of H69 small-cell lung cancer cells causes stable radiation and drug resistance with increased MRP1, MRP2, and topoisomerase IIalpha expression.

Purpose: After standard treatment with chemotherapy and radiotherapy, small-cell lung cancer (SCLC) often develops resistance to both treatments. Our aims were to establish if fractionated radiation treatment alone would induce radiation and drug resistance in the H69 SCLC cell line, and to determine the mechanisms of resistance.

Methods And Materials: H69 SCLC cells were treated with fractionated X-rays to an accumulated dose of 37.