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Biomedical subjects

K C Kim

Publications and source records attributed to K C Kim.

142 records · Page 8Linked to original sources
PubMedDate not supplied

The growth inhibition of hepatoma by gene transfer of antisense vascular endothelial growth factor.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and tumor growth in solid tumors. Therefore, to induce tumor regression, antiangiogenic agents to block VEGF need to be administered repeatedly. METHOD: We constructed the recombinant mammalian expression vector bearing an antisense-VEGF cDNA, pZeoVEGFa. We examined the effect of pZeoVEGFa on the growth of SK-HEP1 hepatoma cells, bovine capillary endothelial (BCE) cells, and tubule formation of BCE cells in fibrin gel. To evaluate the function of pZeoVEGFa in vivo, we implanted SK-HEP1 hepatoma cells subcutaneously into nude mice. RESULTS: In SK-HEP1 hepatoma cells, we showed that the synthesis of VEGF protein was suppressed by the stable and transient transfection of pZeoVEGFa. pZeoVEGFa inhibited the proliferation of BCE cells and significantly suppressed tubule formation of BCE cells. pZeoVEGFa inhibited a morphological change from a round shape to an elongated spindle shape in fibrin gel. When pZeoVEGFa was injected peritumorally by liposomes, tumor growth was inhibited. CONCLUSION: Endothelial cell proliferation, tubule formation and tumor growth may be diminished by down-regulation of endogenous VEGF expression in tumor cells or tissue. These findings indicate that the efficient down-regulation of the VEGF produced by tumor cells using antisense strategies has an antitumor effect. We suggest that VEGF-targeted antiangiogenic gene therapy could be an effective strategy to treat VEGF-producing tumors.

Animals↗
PubMedDate not supplied

Nesidioblastosis and mixed hamartoma of the liver in Beckwith-Wiedemann syndrome: case study including analysis of H19 methylation and insulin-like growth factor 2 genotyping and imprinting.

An infant with persistent hyperinsulinemic hypoglycemia, diffuse nesidioblastosis, and mixed hamartoma of the liver (MHL), in addition to demonstrating clinical, pathologic, and molecular manifestations of Beckwith-Wiedemann syndrome (BWS), is the subject of this report. H19 methylation assay and allelic expression analysis for insulin-like growth factor 2 (IGF2) indicated that the patient was mosaic for paternal isodisomic cells and normal cells in lung tissue, nontumoral liver tissue, tissue from the MHL, and pancreatic tissue. We propose that abundant IGF2 expression during development due to paternal isodisomy resulted in hepatomegaly and islet cell hyperplasia, which led to nesidioblastosis. MHL, by contrast, may have resulted from a decrease in disomic cells, compared with nontumoral liver tissue, which showed an increase in disomic cells. Thus, somatic mosaicism may result in unbalanced tissue growth, which may contribute to the formation of MHL in BWS.

Allelic Imbalance↗
PubMedDate not supplied

Inhaled ATP causes mucin release from goblet cells of intact rats.

Secretion of mucins from airway epithelial cells has been studied almost exclusively using in vitro cell culture systems. Our understanding of in vivo secretion is greatly limited due to the unavailability of both suitable model systems and adequate assays. It has been reported that ATP induces mucin release from the cultured primary tracheal surface epithelial cell, but there is no clear demonstration of the effect of ATP on mucin release in vivo, which is important to understand the mechanism of mucin release in vivo and also to devise means for regulation of mucin release. The objective of this experiment was to see if inhaled ATP could stimulate airway mucin release in intact rats using both enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. The results were: (1) a new monoclonal antibody (mAbRT03) developed against purified rat mucins specifically recognized high-molecular-mass mucins; (2) ELISA results with conventional gel-filtration assay results are virtually superimposable; (3) inhalation of ATP in intact rats resulted in a dose-independent increase in the amount of mucins in the tracheal lavage fluid with a concomitant decrease in the number of mucin-positive cells in the trachea. We conclude that extracellular ATP can stimulate mucin release from the airway in vivo, and the present rat inhalation system combined with ELISA of the airway secretions should serve a useful model for studying the pharmacology of airway mucin secretion in vivo.

Adenosine Triphosphate↗
PubMedDate not supplied

Hydrophobicity of mucin-like glycoproteins secreted by cultured tracheal epithelial cells: association with lipids.

Confluent cultures of primary hamster tracheal surface epithelial cells are highly enriched with secretory cells resembling airway goblet cells. The cultures secrete lipids, most of which appear to be associated with high-molecular-weight mucinlike glycoproteins (HMW MLGP). In the present communication, we examined the nature of the association and analyzed the lipids associated with the secreted HMW MLGP. The HMW MLGP purified in the presence of 4 M guanidinium HCl were highly associated with lipids. When these HMW MLGP were gel filtered using a Sepharose CL-4B column in the presence of detergents, more than 97% of the associated lipids were dissociated from HMW MLGP and eluted in fractions with Kd = 0.70. On the other hand, when [3H]palmitic acid-labeled spent medium was gel filtered, column elution profiles varied among elution buffers, a major change being an appearance of a 3H peak at Kd = 0.70 in the presence of 50 mM sodium acetate, phosphate-buffered saline (PBS), or PBS/sodium dodecyl sulfate, but not with 4 M guanidinium HCl. Lipids associated with MMW MLGP under a "physiological" condition consisted of neutral, phospho-, and glycolipids. We conclude that (1) HMW MLGP secreted from cultured airway epithelial cells are extremely hydrophobic and associated with a variety of lipids, mostly via noncovalent binding, and (2) the degree of the lipid association seems to depend on the ionic environment of the solution.

Animals↗
PubMedDate not supplied

Mucin-like glycoproteins secreted from cultured hamster tracheal surface epithelial cells: their hydrophobic nature and amino acid composition.

Confluent cultures of primary hamster tracheal surface epithelial cells synthesize and secrete high molecular weight mucin-like glycoproteins (HMW MLGP). Secreted HMW MLGP are highly associated with various lipids, indicating that they are extremely hydrophobic. These HMW MLGP are also associated with varying amounts of "small" glycoproteins via hydrophobic interactions and they can be dissociated by heat and detergent treatments. HMW MLGP free of these "small" glycoconjugates have a buoyant density of 1.5 g/ml and can enter 4% but not 7.5% gels during SDS-polyacrylamide gel electrophoresis. Amino acid composition analysis of HMW MLGP free of these "small" glycoproteins shows that they are relatively rich in serine, threonine, and proline, but the total content of these amino acids seems somewhat lower than that of in vivo airway mucins.

Amino Acids↗
PubMedDate not supplied

Imatinib (ST1571) provides only limited selectivity for CML cells and treatment might be complicated by silent BCR-ABL genes.

Very promising results have been obtained in clinical trials on chronic-phase chronic myeloid leukemia (CP-CML) patients treated with imatinib mesylate (IM; Gleevecr, STI571), a BCR-ABL tyrosine kinase inhibitor. However, we found that IM caused considerable inhibition of normal hematopoietic progenitor cells upon treating control bone marrow (BM) cultures. In vitro IM treatment gave a decrease in the yield and size of colonies from BM of untreated CP-CML patients that was only two to three times that from the normal samples. Moreover, about 30% of myeloid progenitors (CFU-GM) from CML BM still formed colonies in the presence of IM, most of which had BCR-ABL RNA. About half of these treated colonies also displayed methylation of the internal ABL Pa promoter, a CML-specific epigenetic alteration, which was used in this study as a marker for BCR-ABL translocation-containing cells. However, ~5-8% of the treated or the untreated CML BM-derived colonies had no detectable BCR-ABL RNA by two or three rounds of RT-PCR despite being positive for the internal standard RNA and displaying hallmarks of CML, either t(9;22)(q34;ql 1) or ABL Pa methylation. Our results indicate that IM is only partially specific for CML progenitor cells compared to normal hematopoietic progenitor cells and suggest that some CML cells may have a silent BCR-ABL oncogene that could interfere with therapy.

Benzamides↗