Induction of versican by ascorbic acid 2-phosphate in dermal papilla cells.
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Ascorbic Acid↗
Biomedical subjects
Moon Kyu Kim
Publications and source records attributed to Moon Kyu Kim.
The hair growth promoting effect of ascorbic acid 2-phosphate, a long-acting Vitamin C derivative.
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Animals↗
Limited effect of CpG ODN in preventing type 1 diabetes in NOD mice.
Type 1 diabetes is considered as Th1 cell mediated autoimmune disease and the suppression of Th1 cells or the activation of Th2 cells has been regarded as a plausible immunologic intervention for the prevention of type 1 diabetogenesis in a rodent model. CpG ODN is an immunostimulatory sequence primarily present in bacterial DNA, viral DNA and BCG. CpG ODN is conventionally classified as a Th1 cell activator, which has been clinically applied to cancer, allergy and infectious disease. Recently, there was a promising report of that CpG ODN administration suppressed the development of type 1 diabetes in NOD mice by inducing Th2 cell mediated cytokine. However, the antidiabetogenic effect of CpG ODN on NOD mice is controversial. Thus, two studies were serially undertaken with various kinds of CpG motif to find a more optimal sequence and administration method. In the first study, CpG ODN was vaccinated four times and pancreatic inflammation and the quantity of serum insulin subsequently evaluated. In the second study, the amounts of IFN gamma and IL-4 in sera were measured as representative cytokines of Th1 and Th2 cells, respectively. As a result, vaccination or continuous injection of CpG ODN failed to show a preventive effect on type 1 diabetogenesis in NOD mice. Structural differences of CpG ODN also had no affect on the result. CpG ODN also consistently showed affect on the pancreatic pathology. The productions of IFN gamma and IL-4 were detected only in the K and D type CpG ODN administration groups. Comparison of the two cytokines leads to the conclusion that CpG ODN generated a Th1-weighted response in both study groups. It was assumed that CpG ODN failed to produce Th2-weighted cytokine milieu, which can overcome the genetically determined phenotype of NOD mice. Given these results, it was concluded that the immunotherapeutic application of CpG ODN on Type 1 diabetes had clear limitations.
Animals↗
URB expression in human dermal papilla cells.
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Animals↗
Two novel mutations of Wiskott-Aldrich syndrome: the molecular prediction of interaction between the mutated WASP L101P with WASP-interacting protein by molecular modeling.
Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and increased susceptibility of infections, with mutations of the WAS gene being responsible for WAS and X-linked thrombocytopenia. Herein, two novel mutations of WAS at T336C on exon 3, and at 1326-1329, a G deletion on exon 10, resulting in L101P missense mutation and frameshift mutation 444 stop, respectively, are reported. The affected patients with either mutation showed severe suppression of WAS protein (WASP) levels, T cell proliferation, and CFSE-labeled T cells division. Because WASP L101 have not shown direct nuclear Overhauser effect (NOE) contact with the WASP-interacting protein (WIP) in NMR spectroscopy, molecular modeling was performed to evaluate the molecular effect of WASP P101 to WIP peptide. It is presumed that P101 induced a conformational change in the Q99 residue of WASP and made the side chain of Q99 move away from the WIP peptide, resulting in disruption of the hydrogen bond between Q99 WASP and Y475 WIP. A possible model for the molecular pathogenesis of WAS has been proposed by analyzing the interactions of WASP and WIP using a molecular modeling study.
Amino Acid Sequence↗
The correlation between cyclooxygenase-2 expression and hepatocellular carcinogenesis.
Overexpression of cyclooxygenase 2 (COX-2) is associated with tumorigenesis in a number of human cancers. Recently, COX-2 overexpression has also been reported in hepatocellular carcinoma (HCC), especially in well-differentiated HCC. However, doubt has been cast on these claims concerning HCC. Here we show by Western blot analysis that COX-2 protein level is higher in the adjacent chronic hepatitis liver than in the tumors themselves. We also show, by immunohistochemical staining, that the mean intensity of COX-2 expression in cirrhotic liver specimens is significantly higher than in normal livers and in moderately-differentiated HCC. In addition, the frequency and level of expression of COX-2 in poorly differentiated HCC was similar to that of well-differentiated HCC. Nevertheless all types of HCC expressed more COX-2 than normal livers, and immunofluorescence staining showed cytoplasmic expression of COX-2 in 7 out of 8 human hepatoma cell lines. Collectively, our data suggest that both chemoprevention and chemotherapy of HCC by COX-2 specific inhibitors should be considered. Our data also suggest that COX-2 may play a role in the advanced stages as well as early stages of hepatocarcinogenesis.
Blotting, Western↗
NS398 inhibits the growth of Hep3B human hepatocellular carcinoma cells via caspase-independent apoptosis.
Overexpression of cyclooxygenase 2 (COX-2) is associated with the development of a number of human cancers including hepatocellular carcinoma (HCC). In addition, NS398, a selective COX-2 inhibitor, has been found to inhibit the growth of COX-2 expressing HCC cell lines. However, the mechanism of this effect remains unclear. Here, we report that NS398 inhibits the growth of the Hep 3B human HCC cell line and that inhibition results from the induction of apoptosis with no evidence of cell cycle arrest. We also show that the extent of apoptosis is greatly influenced by culture conditions. The NS398-induced apoptosis in Hep 3B cells is caspase-independent. Our data point to the feasibility of preventing HCC by means of COX-2 inhibitors, and show that the environment influences the cytotoxic effect of NS398 on cancer cells.
Anti-Inflammatory Agents, Non-Steroidal↗
Bystander-mediated regression of murine neuroblastoma via retroviral transfer of the HSV-TK gene.
Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We investigated the bystander effect of retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase (HSV-TK) gene to murine neuroblastoma cell line (neuro-2a) in vitro and in vivo, and we examined whether the mechanism of bystander effect in neuroblastoma would also depend on connexin-dependent gap junction and/or immune response. A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to ganciclovir (GCV) killing. Implanted mixtures of wildtype cells and HSV-TK transduced cells showed a potent bystander effect upon administration of GCV in A/J mice. HSV-TK/GCV system in murine neuroblastoma induced systemic immunity. Immunohistochemical staining showed many CD4+ and CD8+ cell infiltration but did not show anti-connexin 43+ cells. In conclusion, a strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma might be dependent on immune response and/or on other mechanism such as protein phosphorylation or transfer of apoptotic vesicle, rather than connexin-dependent gap junction.
Animals↗
Growth promotion of HepG2 hepatoma cells by antisense-mediated knockdown of glypican-3 is independent of insulin-like growth factor 2 signaling.
Glypican-3 (GPC3) encodes a cell-surface heparan- sulfate proteoglycan and its expression is frequently silenced in ovarian cancer, mesotheliomas, and breast cancer cell lines and ectopic expression of GPC3 inhibited the growth of these cells, suggesting that GPC3 plays a negative role in cell proliferation. In contrast, up-regulation of GPC3 is often observed in hepatoma, neuroblastoma, and Wilms' tumor. Whether GPC3 plays the same growth inhibitory role in these tumors remains to be studied. Here we report that antisense-mediated knockdown of GPC3 in the HepG2 hepatoma cells significantly promotes the growth of hepatoma cells. In addition, we show that this growth promotion is independent of insulin-like growth factor 2 (IGF2) signaling. Our data suggest that GPC3 plays a growth-suppressing role in hepatoma and provide cell biological evidence inconsistent with the hypothesis that GPC3 acts as a growth suppressor by downregulating IGF2.
Carcinoma, Hepatocellular↗
Blocking endogenous glypican-3 expression releases Hep 3B cells from G1 arrest.
Glypican-3 (GPC3) encodes a cell-surface heparan-sulfate proteoglycan mutated in type 1 Simpson-Golabi-Behmel syndrome (SGBS1), an X-linked overgrowth syndrome. The phenotype of SGBS1 patients and of GPC3 knockout mice suggests that GPC3 plays a negative role in cell proliferation, and an apoptosis-inducing role in specific tissues. Ectopic expression of GPC3 in some cell lines has supported the idea that GPC3 inhibits cell growth. Here we report that blocking endogenous GPC3 expression with an antisense transcript promotes the growth of Hep G2 and Hep 3B hepatoma cell lines. Moreover, antisense inhibition releases Hep 3B cells from cell cycle arrest. Hence, our data further support the notion that GPC3 is an inhibitor of cell proliferation and demonstrate that it modulates cell cycle progression.
Animals↗
Polymorphisms in the melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) genes in Korean vitiligo patients.
We have examined the frequency of SNP polymorphisms within the melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) genes in 114 Korean vitiligo patients and 111 normal controls to assess the association of these loci with vitiligo risk. Using direct sequencing techniques, we found the following five MC1R coding region SNPs: Arg67Gln (G200A), Val92Met (G274A), Ile120Thr (T359C), Arg160Arg (C478A), and Gln163Arg (A488G). Of these, the most common were Val92Met at 14% in patients vs. 9% in controls (P = 0.17) and Gln163Arg at 17% in patients vs. 17% in controls (P = 0.84). Presence of the A allele of Val92Met (G274A) was higher in vitiligo patients [P = 0.12, odds ratio (OR) [95% confidence interval (CI)] = 1.68 (0.86-3.25)]. The other three variants showed a frequency <5% of both patients and controls. The ASIP 3'UTR genotype (g.8818A-G) was also assessed in the same subjects. The frequency of the G allele of 3'UTR in ASIP was 17% in vitiligo and 12% in controls [P = 0.14, OR (95% CI) = 1.49 (0.87-2.54)]. Carriage of the G allele was higher in vitiligo patients [P = 0.17, OR (95% CI) = 1.50 (0.83-2.72)], and those who also carried MC1R Val92Met were more prone to vitiligo [eight of 111 patients vs. four of 111 in controls, P = 0.14, OR (95% CI) = 2.75 (0.71-8.69)]. None of these associations, however, reached statistical significance.
Agouti Signaling Protein↗
Autologous stem cell transplantation for the treatment of neuroblastoma in Korea.
Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.
Adolescent↗
Effect of chronic alcohol ingestion on bone mineral density in males without liver cirrhosis.
BACKGROUND: Osteoporosis in men is an important public health problem. Because of the tendency of the numbers of the elderly population to increase, and age-specific incidence of fractures, it is inevitable that the health burden due to fractures will increase. Chronic alcoholism is associated with other risk factors, such as poor nutrition, leanness, liver disease, malabsorption, vitamin D deficiency, hypogonadism, hemosiderosis, parathyroid dysfunction and tobacco use, and these may contribute to the pathogenesis of bone disease related to alcoholism. Chronic alcohol intake may reduce bone density, but can also increase bone density. It is well established that liver disease also induces bone density changes, thus it is difficult to distinguish the role of liver disease from that of alcohol itself in the bone alterations occurring in patients with chronic alcohol consumption. Chronic male alcoholics, not having liver cirrhosis were studied to assess the effect of chronic alcohol consumption on their bone mineral density. METHODS: The study subjects comprised of 18 chronic heavy drinkers of more than 40 g of alcohol per day for at least 3 years and 18 age-matched controls who drank less than 20 g of alcohol per day. The serum and urinary parameters of bone and mineral metabolism were determined. The bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at four axial sites (lumbar spine, femoral neck, Ward's triangle and trochanter). RESULTS: The alcoholic and control patients drank an average of 97.6 g and 7.2 g of alcohol per day. Osteocalcin, a marker of bone formation, was slightly decreased in alcoholic patients, and deoxypyridinoline, a marker of bone resorption, was slightly increased, but the difference was not statistically significant (p > 0.05). There were no differences between the two groups in the levels of free testosterone, estradiol, 25(OH) vitamin D and parathyroid hormone. The Ward's triangle and trochanter BMDs of the femur were significantly lower in the alcoholics than the controls, and lumbar spine BMD was decreased in proportion to the total alcohol intake in the alcoholics (r = -0.625, p = 0.01). CONCLUSION: We suggest that chronic alcohol consumption induces low bone density in the femur Ward's triangle and trochanter. There was also a significant inverse correlation between the lumbar spine BMD and the total amount of alcohol consumed. Large scaled randomized and prospective studies are needed to clarify the pathogenesis of alcohol-induced osteoporosis.
Absorptiometry, Photon↗
Gene expression profile analysis in human hepatocellular carcinoma by cDNA microarray.
We performed gene expression profiling of normal and hepatocellular carcinoma (HCC) liver tissues using a high-density microarray that contained 3,063 human cDNA. The results of a microarray hybridization experiment from eight different HCC tissues were analyzed and classified by the Cluster program. Among these differentially-expressed genes, the galectin-3, serine/threonine kinase SGK, translation factor eIF-4A, -4B, -3, fibroblast growth factor receptor, and ribosomal protein L35A were up-regulated; the mRNAs of Nip3, decorin, and the insulin-like growth factor binding protein-3 were down-regulated in HCC. The differential expression of these genes was further confirmed by an RT-PCR analysis. In addition, our data suggest that the gene expression profile of HCC varies according to the histological types.
Carcinoma, Hepatocellular↗
Liposome formulations for effective administration of lipophilic malonatoplatinum(II) complexes.
For effective administration of lipophilic trans(+/-)-1,2-diaminocyclohexaneplatinum(II) complexes of malonate derivatives [(dach)PtL, L=allylmalonate (AM), diallylmalonate (DAM), allylbenzylmalonate (ABM), or dibenzylmalonate (DBM)] in aqueous solution, we have applied three different liposome formulations and evaluated their physical and chemical properties, along with their in vitro cytotoxicity. The liposome formulations were composed of DMPC / DMPG [DMPC=1,2-dimyristoyl-sn-glycero-3-phosphocholine, DMPG=1,2-dimyristoyl-sn-glycero-3-(phospho-rac-1-glycerol) (sodium salt)] in different molar ratios (7/3 or 3/7) or an equimolar DOTAP/DOPE formulation (DOTAP=1,2-dioleoyl-3-trimethylammonium propane, DOPE=1,2-dioleoyl-sn-glycero-3-phosphoethanolamine). Preliposomal powders of the platinum complexes were prepared by lyophilization, and reconstituted in aqueous solution to obtain the final liposomal platinum complexes. Due to the lipophilicity of the malonatoplatinum complexes, the entrapment efficiency of drugs within the liposomes was over 90% except for the AM complex, and platinum drug stability was also satisfactory (>90%) in these liposomal systems. In vitro cytotoxicity was tested in human ovarian carcinoma cells sensitive (A2780) and resistant to cisplatin (A2780/PDD). In both cell lines, the liposomal DBM complex was much more cytotoxic than the corresponding DAM and ABM complexes, which means that the more hydrophobic benzyl substituent affords higher cytotoxicity than the allyl substituent in the malonato leaving group. Furthermore, the DBM complex in DMPC/DMPG formulations was effective against both sensitive and resistant A2780 cells (resistance indexes (RI)=1.10-1.49), showing lack of cross-resistance to cisplatin. Therefore, the liposomal DBM complex in the DMPC/DMPG formulations is a promising candidate for stable pharmaceutical liposomal platinum complexes.
Animals↗
Autoimmune hemolytic anemia predominantly associated with IgA anti-E and anti-c.
A patient with warm autoimmune hemolytic anemia (AIHA) due to predominance of immunoglobulin A (IgA) with an Rh specificity, considered to be the first case in Korea, is described. A 13-year-old male patient with severe hemolytic anemia showed a weak reactivity (1+) in the direct antiglobulin test (DAT) by using anti-IgG antiglobulin reagent. This finding, however, could not fully explain the patient's severe AIHA. When anti-IgA reagent was used for the DAT, strong reactivity (4+) was observed and free anti-E and anti-c autoantibodies were also detected by anti-IgA and anti-IgG reagents. The patient's hemoglobin began to rise with the administration of steroids. Because RBCs coated with multiple types of immunoglobulins are associated with more severe hemolysis than those only with IgG, the DATs using anti-IgA and other reagents are needed for the correct diagnosis when the result of DAT is not compatible with patient's clinical manifestations.
Adolescent↗
Mutation in the ED1 gene, Ala349Thr, in a Korean patient with X-linked hypohidrotic ectodermal dysplasia developing de novo.
Hypohidrotic ectodermal dysplasia (HED) is a very rare disease characterized by the virtual absence of eccrine glands, dry skin, scanty hair, and dental abnormalities. It is transmitted by an X-linked recessive gene or rarely an autosomal recessive gene. Therefore it is only males who fully express the condition. It is caused by mutations within the ED1 gene, which encodes a protein, ectodysplasin-A (EDA). Typically there is frontal bossing, saddle nose, pointed chin, a prominent supraorbital ridge with periorbital hyperpigmentation, and absence of teeth. Those affected show great intolerance to heat. In the current absence of effective treatment for many hereditary skin diseases, comprehensive, accurate prenatal or postnatal genetic counseling can provide information to parents at risk of having affected children. We report HED in a 6-year-old boy with an Ala349Thr (GCA --> ACA) missense mutation developed de novo. Both parents and a 16-week gestational age fetus were healthy. We thought direct sequencing analysis for the ED1 gene using peripheral blood or amniotic fluid was preferable for an accurate diagnosis of this disease, although there was some risk of not detecting the mutation. After the results of this study were communicated to the parents, the mother was freed of her guilty feelings of the past 6 years and has now delivered a healthy male infant.
Adult↗