Two ovarian cell lines were derived from the ascites of a patient before and after the onset of resistance to chemotherapy involving cis-platinum, chlorambucil and 5-fluorouracil. Characterization of these lines shows them to have various features in common and some significant differences. Cytologically the lines cannot be distinguished and they both contain high concentrations of oestrogen receptor. However, they do differ with respect to their growth characteristics, karyotype, glutathione content and sensitivity to cis-platinum. The karyotypes of the 2 lines show several marker chromosomes in common but the resistant line contained a chromosome 8 and a 17 which were absent from the earlier sensitive line. This suggests a clonal origin with subsequent divergence to a heterogeneous population.

When used periadventitially in the rabbit arterial injury model, natural arterial HSPGs are effective inhibitors of neointimal formation. In vitro, the HSPGs maintain SMCs in a quiescent state by inhibiting phenotypic change and DNA synthesis. This study suggests that HSPGs may be a natural agent for the treatment of clinical restenosis.

Increasing evidence indicates the potential of olfactory ensheathing cells (OECs) for treating spinal cord injuries. The present study compared proliferation and migration of adult rat and human OECs transplanted into the spinal cord of athymic (immunodeficient) rats. OECs were purified from the nasal lamina propria and prelabeled with a cytoplasmic dye. After OEC injection into the thoracic spinal cord, animals were perfused 4 hr, 24 hr, and 7 days later. Both rat and human OECs showed similar migration. Cells were seen leaving the injection site after 4 hr, and by 7 days both rat and human OECs had migrated approximately 1 mm rostrally and caudally within the cord (rat: 1,400 +/- 241 microm rostral, 1,134 +/- 262 microm caudal, n = 5; human: 1,337 +/- 192 microm rostral, 1,205 +/- 148 microm caudal, n = 6). Proliferation of transplanted OECs was evident at 4 hr, but most had ceased dividing by 24 hr. In 10 animals, the spinal cord was injured by a contralateral hemisection made 5 mm rostral to the transplantation site at the time of OEC transplantation. After 7 days, macrophages were numerous both around the injury and at the transplantation site. In the injured cord, rat and human OECs migrated for shorter distances, in both rostral and caudal directions (rat: 762 +/- 118 microm rostral, 554 +/- 142 microm caudal, n = 4; human: 430 +/- 55 microm rostral, 399 +/- 161 microm caudal, n = 3). The results show that rat and human OECs rapidly stop dividing after transplantation and have a similar ability to survive and migrate within the spinal cord of immunocompromised hosts. OECs migrated less in animals with a concomitant contralateral hemisection.

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Abstract-Percutaneous transluminal coronary angioplasty is a frequently used interventional technique to reopen arteriesthat have narrowed because of atherosclerosis. Restenosis, or renarrowing of the artery shortly after angioplasty, is a major limitation to the success of the procedure and is due mainly to smooth muscle cell accumulation in the artery wall at the site of balloon injury. In the present study, we demonstrate that the antiangiogenic sulfated oligosaccharide, PI-88, inhibits primary vascular smooth muscle cell proliferation and reduces intimal thickening 14 days after balloon angioplasty of rat and rabbit arteries. PI-88 reduced heparan sulfate content in the injured artery wall and prevented change in smooth muscle phenotype. However, the mechanism of PI-88 inhibition was not merely confined to the antiheparanase activity of this compound. PI-88 blocked extracellular signal-regulated kinase-1/2 (ERK1/2) activity within minutes of smooth muscle cell injury. It facilitated FGF-2 release from uninjured smooth muscle cells in vitro, and super-released FGF-2 after injury while inhibiting ERK1/2 activation. PI-88 inhibited the decrease in levels of FGF-2 protein in the rat artery wall within 8 minutes of injury. PI-88 also blocked injury-inducible ERK phosphorylation, without altering the clotting time in these animals. Optical biosensor studies revealed that PI-88 potently inhibited (K i 10.3 nmol/L) the interaction of FGF-2 with heparan sulfate. These findings show for the first time the capacity of this sulfated oligosaccharide to directly bind FGF-2, block cellular signaling and proliferation in vitro, and inhibit injury-induced smooth muscle cell hyperplasia in two animal models. As such, this study demonstrates a new role for PI-88 as an inhibitor of intimal thickening after balloon angioplasty. The full text of this article is available online at http://www.circresaha.org. (Circ Res. 2003;92:e70-e77.)Key Words: phosphomannopentaose sulfate Ⅲ heparanase inhibitor Ⅲ smooth muscle cells Ⅲ neointima formation Ⅲ balloon angioplasty P hosphomannopentaose sulfate (PI-88) is a recently developed synthetic polysulfated oligosaccharide that inhibits the activity of the extracellular matrix-degrading enzyme heparanase. 1 PI-88 is a 2-kDa heparan sulfate mimetic structurally distinct from heparin, a heterogenous mixture of polysaccharide chains of varying length with a molecular weights of 3 to 30 kDa. PI-88 is also structurally and functionally different from small heparin-like polyaromatic anionic-type compounds 2 and other heparan sulfate mimetics. 1 In vivo studies have shown that PI-88 is a potent inhibitor of tumor metastasis and angiogenesis. 1 Human and mammalian toxicology studies demonstrate that PI-88 is welltolerated and has low anticoagulant activity. 3 PI-88 is currently in Phase II clinical trials to assess its therapeutic potential as an anticancer drug and is administered to patients by continuous infusion or repeated injection.Percutaneous transluminal coronary angioplasty (PTCA) is common...