PubMed Health⌕ Search

Biomedical subjects

Hwan-Mook Kim

Publications and source records attributed to Hwan-Mook Kim.

At least 19 recordsLinked to original sources
PubMed2006

B cell-activating factor is a novel diagnosis parameter for asthma.

BACKGROUND: Asthma is a life-threatening immediate-type allergic disease. B cell-activating factor (BAFF) is a key regulator of B lymphocyte development and is required to generate and maintain the mature B cell pool. OBJECTIVES: To investigate the level of BAFF in the serum of asthma patients and the role of BAFF on T cells. METHODS: The BAFF level was measured by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMC) from asthma patients were analyzed by flow cytometry. T8.1 cells were used to test the role of BAFF on T cell-antigen-presenting cell (APC) conjugate formation. RESULTS: The BAFF level in patient serum was elevated relative to normal serum. Immunoglobulin E (IgE) concentration and the percentage of CD3+ T and CD19+ B cells vary according to the serum BAFF level. Patients with high BAFF and high IgE (group II) and those with high BAFF and low IgE (group III) show a high ratio of CD3+ T to CD19+ B cells, and the opposite is seen for patients with low BAFF and high IgE (group I) and those with low BAFF and low IgE (group IV). The addition of BAFF increased PBMC proliferation and T cell-APC conjugate formation. BAFF concentration in serum decreased after treatment with antiasthmatic drugs including glucocorticoids and immunosuppressants. CONCLUSION: These findings suggest that the serum BAFF level is high in both IgE-mediated asthma and non-IgE-mediated asthma and extend our knowledge about the fact that BAFF may play a stimulatory role on the proliferation of T cells. Thus, BAFF could be a parameter to monitor the severity of asthma symptoms.

Antigen Presentation↗
PubMed2006

Reactive oxygen species augment B-cell-activating factor expression.

B-cell-activating factor (BAFF) plays a role in mature B-cell generation and maintenance. Lipopolysaccharide (LPS) activates toll-like receptor 4 (TLR4)-dependent signal transduction and induces ROS production. Here, we investigated BAFF production regulated by reactive oxygen species (ROS). BAFF expression was augmented by LPS stimulation and by serum deprivation that induced ROS production. BAFF expression was inhibited by treatment with various antioxidants including N-acetyl-L-cysteine (NAC). We also investigated BAFF expression in vivo using peroxiredoxin II (PrxII)-deficient mouse spleen cells. PrxII is a member of the antioxidant enzyme family that protects cells from oxidative damage. Constitutive production of endogenous ROS was detected in spleen cells lacking PrxII. Serum BAFF protein level and BAFF transcript expression in splenocytes were significantly higher in PrxII(-/-) mice than wildtype mice. A higher BAFF level is consistent with the higher total number of splenocytes and B220(+)cells. Results were supported by NF-kappaB activation as judged by reduced IkappaBalpha degradation and increased nuclear translocation of p65/RelA with LPS stimulation, serum deprivation, and PrxII deletion. Data suggest that TLR4-mediated BAFF expression was increased by ROS and it was inhibited by PrxII controlling ROS production.

Animals↗
PubMed2006

Delayed occurrence of H-ras12V-induced hepatocellular carcinoma with long-term treatment with cinnamaldehydes.

Cinnamaldehyde from the bark of Cinnamomum cassia has been reported to have antitumor activity mediated by the inhibition of farnesyl transferase. We assessed in vivo the chemo-preventive effect of cinnamaldehydes on H-ras12V-induced hepatocellular carcinoma formation. A mouse model of hepatocellular carcinoma was established by using the transgene of mutated H-ras12V under the regulation of albumin enhancer/promoter. When treated with cinnamaldehyde for 10 weeks, hepatic tumor development was delayed with 2'-benzoyloxycinnamaldehyde (BCA) compared with control hepatocellular carcinoma formation. The effect of 2'-hydroxycinnamaldehyde (HCA) was comparable. The number of lesions and the size of each lesion were significantly reduced by BCA. Cell proliferation in the lesion was detected by incorporation of 5-bromo-2'-deoxyuridine (BrdU). BCA increased the number of splenocytes, concanavalin A-stimulated splenocyte proliferation and the infiltration of lymphocytes into liver. Data suggest that the delayed hepatic tumor development observed with BCA could be mediated by a long-term immunostimulating effect on T cells.

Acrolein↗
PubMed2006

Human endogenous retrovirus HERV-H family in human tissues and cancer cells: expression, identification, and phylogeny.

HERV-H family is the most abundant HERV families in the human genome with more than 1000 copies including full-length, truncated form, and solitary LTRs. We investigated envelope (env) gene fragments of HERV-H family in various human tissues and cancer cells. The env fragments were detected in mRNA of several human tissues (placenta, skeletal muscle, spleen, and thymus) and cancer cells (RT4, BT-474, HCT-116, TE-1, UO-31, Jurkat, HepG2, A549, MCF7, OVCAR-3, MIA-PaCa-2, PC3, LOX-IMVI, AZ521, 2F7, U-937, and C-33A) by RT-PCR approach. The RT-PCR products were cloned and sequenced. New 12 clones from human tissues and 48 clones from cancer cells of env gene sequences belonging to the HERV-H family showed 84.3-98.1% sequence similarity to that of HERV-H (AF108843). Deduced amino acid sequences of 60 clones from human tissues and cancer cell lines showed multiple frameshifts and termination codons caused by deletion/insertion or point mutation with the exception of eight clones as following: HHE9-1, HHE9-5 (skeletal muscle), HHE10-5 (spleen), CHE10-9 (MCF7), CHE12-4, CHE12-5 (MIA-PaCa-2), and CHE18-1, CHE18-3 (C-33A) to that of HERV-H (AF108843). A phylogenetic tree of the HERV-H family was constructed to understand their relationship, indicating that they were divided into three groups, one major (group I) and two minor (group II and III), through sequence divergence. The HERV-H families in group I has been proliferated on human genome during hominoid evolution. These active HERV-H elements are worthy of further investigations as potential pathogenic effects to various human diseases including cancers.

Amino Acid Sequence↗
PubMed2005

Synthesis and biological evaluation of dimeric cinnamaldehydes as potent antitumor agents.

It has been reported that 2-hydroxycinnamaldehyde and 2-benzoyl-oxycinnamaldehyde inhibited the activity of farnesyl protein transferase, angiogenesis, cell-cell adhesion, and tumor growth in vivo model. In order to improve its anti-tumor activity, dimeric cinnamaldehydes have been synthesized based on 2-hydroxycinnamaldehyde. The synthesized compounds strongly inhibited the growth of human colon tumor cells with GI50 values of 0.6-10 microM. Especially, 2-piperazine derivative blocked in vivo growth of human colon tumor xenograft in nude mice at 10 mg/kg. It was found that their anti-tumor effects induce apoptosis and cell cycle arrest at G2/M phase by the compounds. It was confirmed by detection of apoptosis markers such as activated caspase-3 and cleaved PARP, and cell cycle analysis. The dimeric compounds also inhibited Cdc25B phosphatase which is essential for preinitiating G2/M transition and S phase progression.

Acrolein↗
PubMed2005

Cyclopentenediones, inhibitors of farnesyl protein transferase and anti-tumor compounds, isolated from the fruit of Lindera erythrocarpa Makino.

Four cyclopentenediones, farnesyl protein transferase inhibitors, and anti-tumor compounds were isolated from the methanolic extract of the fruits of Lindera erythrocarpa Makino (Lauraceae). The structure of the compounds was determined by spectral data including NMR and mass spectrometry, and cyclopentenediones such as methyllinderone (1), methyllucidone (2), lucidone (3), and linderone (4) were identified by comparing their reported spectral data with that of the literature values. Compounds 1-4 inhibited farnesyl protein transferase with IC50 value of 55.3+/-4.1, 42+/-1.9, 103+/-5.1, and 40+/-3.5 microM, respectively. Isolated compounds also inhibited the growth of various human cancer cell lines in a dose-dependent manner. Especially, Compounds 1 and 2 selectively inhibited the growth of H-ras-transformed rat-2 cell lines in comparison with normal rat-2 cells with a GI50 value of 0.3 and 0.85 microM, respectively. Methyllucidone strongly inhibited the growth of human cancer cells and colon tumor xenografted in nude mice. The anti-tumor effects of the compound were further confirmed with caspase-3 activation and degradation of PARP. The results suggest that methyllucidone can be a potential anti-cancer agent against H-ras-transformed tumor and will also be a good lead molecule for the development of anti-tumor drug.

Alkyl and Aryl Transferases↗
PubMed2005

BRD-glucan exhibits potent immunochemotherapeutic activity in vitro and in vivo.

We carried out in vitro and in vivo assays to investigate the immunomodulatory and immunochemotherapeutic action mechanism of BRD-glucan, a high molecular weight ( approximately 3,500 kDa) polysaccharide isolated from Aureobasidium sp, and assessed the efficacy of BRD-glucan/adriamycin co-treatment of animal cancer models. RT-PCR and suspension hemolytic, plaque forming, wounding, invasion and cell proliferation assays were utilized to investigate the in vitro immunochemotherapeutic effects of BRD-glucan. In vivo, the effects of BRD-glucan and BRD-glucan/adriamycin co-treatment were tested in a B16 melanoma initiation model and in C57BL/6 mice. In vitro, BRD-glucan did not affect the cellular wounding response or invasion activity; treatment with BRD-glucan led to increase proliferation of B cells, natural killer cells and macrophages, but not T cells. In addition, we found that the BRD-glucan activation of B cells and macrophages was dependent on Toll-like receptor2 (TLR2) and TLR4, which play important roles in innate and adaptive immunity. In vivo, BRD-glucan/adriamycin co-treatment effectively reduced the number and size of metastatic colonies. Based on the results of our in vitro and in vivo toxicity, safety and immunochemotherapy assays, we propose that BRD-glucan is a promising immunochemotherapeutic anti-tumor agent.

Animals↗
PubMed2004

Human endogenous retroviral elements belonging to the HERV-S family from human tissues, cancer cells, and primates: expression, structure, phylogeny and evolution.

A new human endogenous retrovirus family (HERV-S) was recently identified from the human chromosome X. The HERV-S was 6.7 kb in length with typical retroviral structure (LTR-gag-pol-env-LTR). We investigated pol fragments of HERV-S family in various human tissues and cancer cells. The pol gene was expressed in only brain and thymus among human tissues (brain, prostate, testis, heart, kidney, liver, lung, placenta, skeletal muscle, spleen, thymus, uterus), whereas the pol gene was detected in various cancer cell lines (RT4, PFSK-1, BT-474, HCT-116, Jurkat, HepG2, MCF7, OVCAR-3, MIA-PaCa-2, PC3, LOX-IMVI, AZ521, 2F7, and C-33A) except for TE-1, UO-31, A549, and U-937 by RT-PCR analysis. Expression and sequencing data of the 33 clones imply that the pol gene of HERV-S family is more active in cancer cells than in human tissues, which may have transcriptional potential role related to various human cancers. Phylogenetic analysis of HERV-S pol family distinctively divided into three groups (group I, II, and III) through evolutionary divergence in primate evolution. Evolutionary divergence of the HERV-S family by PCR amplification and sequence analysis indicated that they were integrated into the primate genomes approximately 43 Myr ago and have been evolved rate of 0.3% nucleotide differences per Myr during primate evolution.

Amino Acid Sequence↗
PubMed2004

Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated with lung cancer.

RUNX family transcription factors are integral components of TGF-beta signaling pathways and have been implicated in cell cycle regulation, differentiation, apoptosis, and malignant transformation. It was noted previously that allele loss and loss of expression of RUNX3 are causally involved in gastric carcinogenesis. Our results demonstrate that RUNX3 is inactivated by aberrant DNA methylation in approximately 19% of lung cancer cell lines and 24% of primary lung cancer specimens. RUNX3 methylation is tumor-specific, since it is not observed in surrounding normal lung tissues. Our results suggest that loss of RUNX3 expression by DNA hypermethylation is frequently associated with the evolution of lung cancer.

Base Sequence↗
PubMed2004

Synthesis and cytotoxic activity of 1-(1-benzoylindoline-5-sulfonyl)-4-phenylimidazolidinones.

The novel 1-(1-benzoylindoline-5-sulfonyl)-4-phenyl-4,5-dihydroimidazolones 2 shows highly potent and broad cytotoxicities. Their cytotoxicities against human lung carcinoma A549, human chronic myelogenous leukemia K562, and human ovarian adenocarcinoma SK-OV-3 are compatible with doxorubicin. Compound 2p (1-[(4-aminobenzoyl)indoline-5-sulfonyl])-4-phenyl-4,5-dihydroimidazolone) exhibits a cytotoxicity that is far more potent than doxorubicin and also exhibits highly effective antitumour activities against murine (3LL, Colon 26) and human xenograft (NCI-H23, SW620) tumor models.

Animals↗
PubMed2004

Synthesis and cytotoxicity of 2,5-dihydroxychalcones and related compounds.

A series of 2, 5-dihydroxychalcones and related compounds were synthesized, and their cytotoxicities against tumor cell lines and human umbilical venous endothelial cells (HUVEC) evaluated. It was found that chalcones, with electron-withdrawing substituents on an A ring, exhibited significant cytotoxicities. Among the synthesized compounds, 2'-chloro-2, 5-dihydroxychalcone (9) was most potent, with an IC50 value as low as 0.31 microg/mL. This compound also exhibited a significant cytotoxic selectivity toward HUVEC.

Animals↗
PubMed2004

New constituents from Crinum latifolium with inhibitory effects against tube-like formation of human umbilical venous endothelial cells.

Six compounds (1-6) were isolated from the methanol extract of Crinum latifolium by bioassay-guided separation. Among the six isolates, compounds 2 and 6 were new metabolites. Their structures were established as 4-senecioyloxymethyl-3,4-dimethoxycoumarin (2) and 5,6,3'-trihydroxy-7,8,4'-trimethoxyflavone (6) based on spectroscopic analyses. Compound 2 was found to be strongly inhibitory against the in vitro tube-like formation of human umbilical venous endothelial cells (HUVECs) while manifesting no cytotoxicity in tumor cell lines (B16F10, HCT116). Significant inhibitory activity (inhibition percentage, 53.5%) was still observed at concentrations as low as 1 microg/mL. Compound 6 showed a modest inhibitory effect on the tube-like formation of HUVECs. Other compounds, including cycloartenol (1), 4',7-dihydroxy-3'-methoxyflavan (3), 4',7-dihydroxyflavan (4), and 2',4',7-trihydroxydihydrochalcone (5) were found to be nearly inactive.

Angiogenesis Inhibitors↗
PubMed2003

2'-benzoyloxycinnamaldehyde induces apoptosis in human carcinoma via reactive oxygen species.

2'-hydroxycinnamaldehyde (HCA) has been shown to have inhibitory effects on farnesyl protein transferase in vitro, angiogenesis, and tumor cell growth. However, mechanism for these inhibitions remains unknown. As a derivative of HCA, BCA (2'-benzoyl-oxycinnamaldehyde) was synthesized by replacing hydroxyl group with benzoyl-oxyl group. When p53-mutated cancer cell lines (MDA-MB-231 breast cancer cell and SW620 colon cancer cell) were treated with 10 microM HCA or BCA, it induced growth arrest and apoptosis of tumor cells. Markers of apoptosis such as degradations of chromosomal DNA and poly(ADP-ribose) polymerase and activation of caspase-3 were detected after HCA or BCA treatment. BCA-induced apoptosis was blocked by pretreatment of cells with anti-oxidants, glutathione, or N-acetyl-cysteine. In addition, BCA-induced activation of caspase-3 and degradation of poly(ADP-ribose) polymerase were abolished by pretreatment of cells with the anti-oxidants. These results suggest that reactive oxygen species are major regulator of BCA-induced apoptosis. HCA or BCA-induced accumulation of reactive oxygen species was detected by using DCF-DA, an intracellular probe of oxidative stress. Furthermore, when BCA (100 mg/kg) was administrated intraperitoneally or orally into a nude mouse, it inhibited >88 or 41% of tumor growth, respectively, without any detectable weight change. These results suggest that BCA is a good drug candidate for cancer therapy.

Acetylcysteine↗
PubMed2003

Water soluble prodrugs of the antitumor agent 3-[(3-amino-4-methoxy)phenyl]-2-(3,4,5-trimethoxyphenyl)cyclopent-2-ene-1-one.

Fourteen prodrugs of the antitumor agent 3-[(3-amino-4-methoxy)phenyl]-2-(3,4,5-trimethoxyphenyl)cyclopent-2-ene-1-one (1) were prepared to improve its water solubility and potency. These prodrugs include alpha-amino acid (1a-1h), aliphatic amino acid (1i-1l), phosphoramidate (1m), and phosphate (1n) derivatives. All of the prodrugs showed improved water solubility. A number of the amino acid prodrugs (1a, 1b, 1d-1f, 1h, 1j, and 1k) exhibited more potent antitumor activity compared to the parent compound (1). The phosphate prodrug 1n also offered a potent antitumor activity, but the phosphoramidate 1m did not show any antitumor activity in vivo. None of the prodrugs exhibited significant toxicities in mice. These results indicate that the design and preparation of the amino acid prodrugs (1a, 1b, 1d-1f, 1h, 1j, and 1k) and phosphate prodrug (1n) are beneficial for enhancing the antitumor activity of 1. The similar approaches may be used to improve water solubility and bioactivity of other poorly soluble aromatic amines.

Animals↗
PubMed2003

Antiinvasive, antiangiogenic and antitumour activity of Ephedra sinica extract.

A water fraction (EW), the remaining water phase from the methanol extract of Ephedra sinica after extraction with ethyl acetate and butanol, has been investigated for its antiangiogenic, antiinvasive and antitumour activities. It was observed that EW, at 30 micro g/mL, a non-cytotoxic concentration, inhibited the tube formation induced by human umbilical venous endothelial cells and the invasion of B16F10 melanoma cells through a matrix membrane by more than 90%. At 30 mg/kg/day, the inhibitory activity of EW on the growth of a tumour mass in BDF1 mice inoculated with B16-F10 murine melanoma cells was comparable to that of adriamycin (ADR) administered at 2 mg/kg/day. From these results, it could be postulated that the antitumour activity of the water fraction might be attributed to its antiangiogenic and antiinvasive activities.

Angiogenesis Inhibitors↗
PubMed2003

Inhibitory effects of Vietnamese medicinal plants on tube-like formation of human umbilical venous cells.

Seven of 58 plant materials from Vietnamese medicinal plants showed strong to moderate inhibitory activity on the tube-like formation induced by human umbilical venous endothelial cells in the in vitro angiogenesis assay. These plant materials include the herb of Ephedra sinica, leaves and stem of Ceiba pentandra, seed of Coix lachryma-jobi, rhizome of Drynaria fortunei, fruits and stem of Illicium verum and stem of Bombax ceiba. Of these, the methanol extracts of the herb of Ephedra sinica and stem of -Ceiba pentandra exhibited the strongest activities with inhibition percentages of 89.3% and 87.5% at 30 and 100 microgram/mL, respectively.

Angiogenesis Inhibitors↗
PubMed2003

Cytotoxic 2',5'-dihydroxychalcones with unexpected antiangiogenic activity.

A series of 2',5'-dihydroxychalcones were synthesized and evaluated for cytotoxicity against tumor cell lines and human umbilical venous endothelial cells (HUVEC). It was found that chalcones with electron-withdrawing substituents on the B ring exhibited potent cytotoxicity against a variety of tumor cell lines while compounds with electron-releasing groups were less potent in general. Those compounds with B ring replaced by extended or heteroaromatic rings exhibited significant bioactivity. Several compounds were shown to have marked cytotoxic selectivity towards HUVECs. Especially, among the synthesized compounds, 2-chloro-2',5'-dihydroxychalcone (2-3) showed the highest selectivity index up to 66 in comparison to HCT116 cells. This compound also exhibited strong inhibitory effects on the HUVEC tube formation in an in vitro model. When administered into BDF1 mice bearing Lewis lung carcinoma cells at 50 mg kg(-1) day(-1), 2-3 was found to inhibit the growth of tumor mass by 60.5%.

Angiogenesis Inhibitors↗