TEP1, the yeast homolog of the human tumor suppressor gene PTEN/MMAC1/TEP1, is linked to the phosphatidylinositol pathway and plays a role in the developmental process of sporulation.

PTEN/MMAC1/TEP1 (PTEN, phosphatase deleted on chromosome ten; MMAC1, mutated in multiple advanced cancers; TEP1, tensin-like phosphatase) is a major human tumor suppressor gene whose suppressive activity operates on the phosphatidylinositol pathway. A single homologue of this gene, TEP1 (YNL128w), exists in the budding yeast Saccharomyces cerevisiae. Yeast strains deleted for TEP1 exhibit essentially no phenotype in haploids; however, diploids exhibit resistance to the phosphatidylinositol-3-phosphate kinase inhibitor wortmannin and to lithium ions. Although rates of cancer increase with age, neither tep1 haploids nor diploids have altered life spans. TEP1 RNA is present throughout the cell cycle, and levels are dramatically up-regulated during meiotic development. Although homozygous tep1 mutants initiate the meiotic program and form spores with wild-type kinetics, analysis of the spores produced in tep1 mutants indicates a specific defect in the trafficking or deposition of dityrosine, a major component of yeast spore walls, to the surface. Introduction of a common PTEN mutation found in human tumors into the analogous position in Tep1p produces a nonfunctional protein based on in vivo activity. These studies implicate Tep1p in a specific developmental trafficking or deposition event and suggest that Tep1p, like its mammalian counterpart, impinges on the phosphatidylinositol pathway.

CT visualization of blood pool in rats by using long-circulating, iodine-containing micelles.

RATIONALE AND OBJECTIVES: Small, long-circulating particulate carriers of contrast agents, such as micelles, are potentially useful in computed tomographic (CT) blood-pool imaging. An iodine-containing amphiphilic block-copolymer consisting of iodine-substituted poly-L-lysine (MPEG-iodolysine) forms micelles in an aqueous solution. The biodistribution and CT depiction of these radiopaque micelles were therefore studied in rats. MATERIALS AND METHODS: MPEG-iodolysine micelles were synthesized and injected into rats via the tail vein at a dose of 170 mg iodine per kilogram. Three animals were used, and tissue enhancement was followed on serial CT scans. RESULTS: MPEG-iodolysine block-copolymer forms particulates with an average diameter of 80 nm and an iodine content of 33.8%. After intravenous injection into rats, the agent produced noticeable and sustained enhancement of the blood pool (aorta and heart), liver, and spleen for least 3 hours. CONCLUSION: In rats, MPEG-iodolysine micelles were a long-lived blood-pool contrast agent useful for CT.

Stable polymeric micelles: lymphangiographic contrast media for gamma scintigraphy and magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Amphiphilic biocompatible polyoxyethylene (PEO)-based polymers form particles (micelles) that are 10-50 nm in diameter. In the current research, we successfully incorporated amphiphilic indium-111 (111In) and gadolinium chelates into these particles and used them as particulate contrast media in percutaneous lymphography. METHODS: Micelles of amphiphilic PEO-lipid conjugates were loaded with 111In and gadolinium diethylenetriamine pentaacetic acid-phosphatidylethanolamine (Gd-DTPA-PE) and were injected subcutaneously into the rabbit's paw. Corresponding images of local lymphatics were acquired using a gamma camera and a magnetic resonance (MR) imager. RESULTS: The entire lymphatic chain from the paw to the thoracic duct could be visualized using 111In micelles after injection site massage. T1-weighted MR images of the primary lymph node and collecting vessels were obtained within 4 min after administration of gadolinium micelles and massage. CONCLUSION: Polymeric PEO-containing micelles can be loaded with diagnostic metals and, on subcutaneous injection, can visualize elements of lymphatic system. The major fraction of injected micelles stays within the lymph fluid, thus serving as lymphangiographic agents for indirect MR or gamma lymphography.