On the interaction of fluorophore-encapsulating PEGylated lecithin liposomes with hamster and human platelets.

Polyethylene glycol (PEG)-grafted phosphatidylcholine liposomes are used as drug carriers due to their low immunogenicity and prolonged circulation time. The interaction between sterically stabilized lecithin liposomes and platelets has not been investigated before, and deserves to be subjected to scrutiny inasmuch as the uptake of liposomes by platelets could be detrimental for drug delivery and primary hemostasis. Consequently, the interaction between resting and convulxin-activated hamster and human platelets and calcein- or 5,6-carboxyfluorescein-encapsulating PEGylated liposomes composed of distearoyl- and dipalmitoyl phosphatidylcholine and PEG-derivatized distearoyl phosphatidylethanolamine was investigated by flow cytometry, confocal microscopy, and a glass capillary thrombosis model.

High cytotoxicity of cisplatin nanocapsules in ovarian carcinoma cells depends on uptake by caveolae-mediated endocytosis.

Purpose: Cisplatin nanocapsules, nanoprecipitates of cisplatin encapsulated in phospholipid bilayers, exhibit increased in vitro toxicity compared with the free drug toward a panel of human ovarian carcinoma cell lines. To elucidate the mechanism of cell killing by nanocapsules and to understand the cell line dependence of nanocapsule efficacy, the route of uptake and the intracellular fate of the nanocapsules were investigated.

Experimental Design: Intracellular platinum accumulation and cisplatin-DNA-adduct formation were measured in cell lines that differ in sensitivity to cisplatin nanocapsules.

Antitumor activity and biodistribution of cisplatin nanocapsules in nude mice bearing human ovarian carcinoma xenografts.

Cisplatin nanocapsules represent a novel lipid formulation of the anticancer drug cis-diamminedichloridoplatinum(II) (cisplatin), characterized by an unprecedented cisplatin-to-lipid molar ratio, and exhibiting strongly increased in-vitro cytotoxicity compared with the free drug. In this study, antitumor efficacy and biodistribution of PEGylated cisplatin nanocapsules were compared with those of the free drug in a mouse tumor model. Nude mice bearing human ovarian carcinoma OVCAR-3 xenografts were treated twice with a 1-week interval by intravenous administration of cisplatin nanocapsules or cisplatin in solution, and the growth inhibitory effects were determined by measurement of tumor volumes.

Nanocapsules: a novel lipid formulation platform for platinum-based anti-cancer drugs.

Platinum-based anti-cancer agents have been used for many years to treat many different types of cancer. However, the efficacy of these drugs is limited by serious side effects. One of the strategies to reduce the side effects is encapsulation of the drug in a lipid formulation.

Carboplatin nanocapsules: a highly cytotoxic, phospholipid-based formulation of carboplatin.

Platinum-based drugs are widely used in cancer chemotherapy. However, their clinical use is limited by systemic toxicity, rapid blood clearance, and the occurrence of resistance. Our research is aimed at increasing the therapeutic index of these drugs by encapsulation in a lipid formulation.

Impaired cisplatin influx in an A2780 mutant cell line: evidence for a putative, cis-configuration-specific, platinum influx transporter.

The effectiveness of platinum drugs in the treatment of cancer is hindered by intrinsic and acquired resistance. The cause of clinical resistance to platinum compounds is still unknown. In an attempt to identify new cellular mechanisms of cisplatin resistance, a one-step cisplatin-selection procedure was used to generate resistant sublines of the platinum sensitive A2780 ovarian cancer cell line.

The Rac activator Tiam1 is required for (alpha)3(beta)1-mediated laminin-5 deposition, cell spreading, and cell migration.

The Rho-like guanosine triphosphatase Rac1 regulates various signaling pathways, including integrin-mediated adhesion and migration of cells. However, the mechanisms by which integrins signal toward Rac are poorly understood. We show that the Rac-specific guanine nucleotide exchange factor Tiam1 (T-lymphoma invasion and metastasis 1) is required for the integrin-mediated laminin (LN)-5 deposition, spreading, and migration of keratinocytes.

Insulin-like growth factor I triggers nuclear accumulation of cyclin D1 in MCF-7S breast cancer cells.

Stimulation of the breast cancer-derived MCF-7S cell line with insulin-like growth factor I (IGF-I; 20 ng/ml) leads to enhanced expression of cyclin D1, hyperphosphorylation of pRb, DNA synthesis, and cell division. 17beta-Estradiol (E(2); 10(-9) m) is not able to stimulate proliferation of MCF-7S cells, although addition of E(2) to serum-starved cells does result in induction of cyclin D1. However, in combination with submitogenic amounts of IGF-I (2 ng/ml), E(2) induces cell proliferation.

Synergistic proliferative action of insulin-like growth factor I and 17 beta-estradiol in MCF-7S breast tumor cells.

We have analyzed the mechanism by which the combination of insulin-like growth factor I (IGF-I) and 17 beta-estradiol (E2) induces cell cycle progression in MCF-7S cells. This cell line differs from many other breast cancer-derived cell lines in that E2 (1 nM) does not induce cell cycle progression, whereas the combination of submitogenic concentrations of IGF-I (2 ng/ml) and E2 does. We find that addition of IGF-I to MCF-7S cells leads to a dose-dependent activation of the IGF type I receptor and of the MAP kinase and PI3-kinase signaling pathways.