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Biomedical subjects

E S Kim

Publications and source records attributed to E S Kim.

At least 37 records · Page 2Linked to original sources

Epidermal growth factor receptor biology (IMC-C225).

Treatment of solid tumors despite improved techniques in detection, surgery, radiation therapy, and chemotherapy remains difficult. Therefore, strategies to improve efficacy in accord with safety are needed. Many epithelial cancers have been found to overexpress the receptor to epidermal growth factor (EGFR), including head and neck, breast, colon, lung, prostate, kidney, ovary, brain, pancreas, and bladder. Because overexpression of EGFR has been associated with an overall poor prognosis in patients with cancer, a number of strategies to block or downregulate EGFR have been developed to inhibit tumor proliferation and improve overall clinical outcome. These include monoclonal antibodies to the EGFR, tyrosine kinase inhibitors, ligand-linked toxins, and antisense approaches. Antibodies such as IMC-C225 specifically target EGF receptors, whereas tyrosine kinase inhibition by many small molecules is less specific. Ultimately, IMC-C225 may prove to become a valuable contributor in the treatment of cancer. This report will focus on IMC-C225, a novel monoclonal antibody that targets the EGFR.

Antibodies, Monoclonal↗

Pseudonocardia kongjuensis sp. nov., isolated from a gold mine cave.

The taxonomic position of an isolate that was recovered from a gold mine cave near Kongju, Republic of Korea, was determined by 16S rDNA sequence studies and chemotaxonomic characterization. Comparative studies of 16S rDNA sequences indicated that this organism was phylogenetically related to members of the genus Pseudonocardia, branching outside a cluster encompassing Pseudonocardia autotrophica and Pseudonocardia compacta. The affiliation to the genus was also supported by the cell chemistry, which was represented by a type IV cell wall, MK-8(H4) as the major menaquinone, a phospholipid type PIII pattern (phosphatidylcholine as a diagnostic phospholipid) and a DNA G+C content of 71 mol%. The fatty acid profile contained saturated, unsaturated and 10-methyl branched fatty acids, but tuberculostearic acid and hydroxy fatty acids were not present. The isolate differed from its phylogenetic neighbours in the presence of phosphatidylethanolamine, dodecanoate, 16-methylheptadecenoate and 16-methylheptadecanoate and the absence of phosphatidylinositol mannoside and phosphatidylmethylethanolamine. The unique combination of physiological properties, the cellular fatty acid profile and DNA-DNA hybridization data indicates that this organism is readily differentiated from the type strains of all of the validly published species of the genus Pseudonocardia. The name Pseudonocardia kongjuensis sp. nov. is proposed for the type strain, LM 157T (= IMSNU 50583T = KCTC 9990T = DSM 44525T).

Actinomycetales↗

Modulation of actinorhodin biosynthesis in Streptomyces lividans by glucose repression of afsR2 gene transcription.

While the biosynthetic gene cluster encoding the pigmented antibiotic actinorhodin (ACT) is present in the two closely related bacterial species, Streptomyces lividans and Streptomyces coelicolor, it normally is expressed only in S. coelicolor-generating the deep-blue colonies responsible for the S. coelicolor name. However, multiple copies of the two regulatory genes, afsR and afsR2, activate ACT production in S. lividans, indicating that this streptomycete encodes a functional ACT biosynthetic pathway. Here we report that the occurrence of ACT biosynthesis in S. lividans is determined conditionally by the carbon source used for culture. We found that the growth of S. lividans on solid media containing glucose prevents ACT production in this species by repressing the synthesis of afsR2 mRNA; a shift to glycerol as the sole carbon source dramatically relieved this repression, leading to extensive ACT synthesis and obliterating this phenotypic distinction between S. lividans and S. coelicolor. Transcription from the afsR2 promoter during growth in glycerol was dependent on afsR gene function and was developmentally regulated, occurring specifically at the time of aerial mycelium formation and coinciding temporally with the onset of ACT production. In liquid media, where morphological differentiation does not occur, ACT production in the absence of glucose increased as S. lividans cells entered stationary phase, but unlike ACT biosynthesis on solid media, occurred by a mechanism that did not require either afsR or afsR2. Our results identify parallel medium-dependent pathways that regulate ACT biosynthesis in S. lividans and further demonstrate that the production of this antibiotic in S. lividans grown on agar can be modulated by carbon source through the regulation of afsR2 mRNA synthesis.

Anthraquinones↗

Aortic dissection: percutaneous management with a separating stent-graft--preliminary results.

The authors used a separating stent-graft to treat Stanford type B aortic dissection. The separating stent-graft consists of two stents: a stent-graft and an inner bare stent. The separating stent-graft has three parts: a proximal stent, a graft made of synthetic polyester textile fiber, and a distal stent. A 12-F introducing sheath was used. After the separating stent-graft was placed, false-lumen thrombosis was evident in all six patients during a follow-up period of 206 days. The major advantages of this technique are that a cutdown and blood pressure control are not required.

Adult↗

IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody, for treatment of head and neck cancer.

Squamous cell carcinoma (SCC) of the head and neck (H&N) remains a clinical challenge due to its high rate of locoregional disease recurrence. The importance of the epidermal growth factor receptor (EGFR) in the development and progression of many solid tumours (including SCC of the H&N) is well understood; increased expression is associated with enhanced tumour invasion, resistance to chemotherapy and decreased patient survival. Several approaches have been developed to achieve EGFR blockade as an anticancer treatment strategy, including an anti-EGFR monoclonal antibody (mAb), IMC-C225, which competitively binds to the extracellular receptor site to prevent binding by natural EGFR ligands (EGF and TGF-alpha). Preclinical studies evaluating this chimeric mAb in human cancer cell lines in vitro and human tumour xenografts in vivo have demonstrated its potent antitumour activity. The clinical efficacy of IMC-C225 appears to involve multiple anticancer mechanisms, including inhibition of cell cycle progression, induction of apoptosis, anti-angiogenesis, inhibition of metastasis and its ability to enhance the response to chemotherapy and radiation therapy. Phase I studies of IMC-C225 combined with chemotherapy or radiation for SCC of the H&N demonstrate excellent response rates in patients with recurrent or refractory disease. Phase II and III trials examining the efficacy and safety of these combinations are currently underway. To date, IMC-C225 has been well-tolerated, with skin rashes and allergic reactions being the most clinically important adverse events reported. IMC-C225 displays dose-dependent elimination characteristics and a half-life of approximately 7 days. Current recommendations for dosing include a 400 mg/m2 loading dose, followed by weekly infusions of 250 mg/m2.

Animals↗

Potential role of caspase-3 and -9 in arsenic trioxide-mediated apoptosis in PCI-1 head and neck cancer cells.

Arsenic trioxide (As2O3) has been shown to inhibit the proliferation of hematologic malignant cells. Previously, we reported that As2O3 had an antitumoral effect in head and neck cancer. Here, we investigated the induction of apoptosis and its mechanism in PCI-1 head and neck squamous carcinoma cells, after treatment with As2O3. Treatment with 2 microM of As2O3 caused apoptosis in PCI-1 cells following 3 days of exposure, which was detected by the annexin V-PI and DAPI staining methods. The cell death population was markedly increased, being 88% larger than the As2O3-untreated control cells. To address the mechanism of apoptosis, a Western blot assay was performed, showing that Bax was up-regulated without a change in Bcl-2. Activation of caspase-9 during As2O3-induced apoptosis was substantiated by monitoring the proteolysis of the caspase-9, which was associated with an increase of Apaf-1 and cytochrome c protein. PCI-1 cells rapidly changed the mitochondria membrane potential (DeltaPsim) after addition of As2O3. Furthermore, activation of caspase-3 was demonstrated by monitoring the proteolysis of the caspase-3 and by measuring caspase-3 activity with a fluorogenic substrate, which was associated with the cleavage of poly(ADP-ribose) polymerase. To examine the in vivo effect of As2O3, C3H mouse inoculated with syngenic SCC7 cells was treated by intratumoral injection of As2O3 (300 microg) every day, demonstrating that tumor mass was dramatically reduced on day 4, and revealed induction of apoptosis by TUNEL assay. These results suggest that apoptosis of PCI-1 cells by As2O3 is induced by activation of caspase-3 via cytochrome c, caspase-9 and Apaf-1 complex.

Animals↗

The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial.

Second primary tumors (SPTs) develop at an annual rate of 3-7% in patients with head and neck squamous cell cancer (HNSCC). In a previous Phase III study, we observed that high doses of 13-cis-retinoic acid reduced the SPT rate in this disease. In 1991, we launched an intergroup, placebo-controlled, double-blind study to evaluate the efficacy of low-dose 13-cis-retinoic acid in the prevention of SPTs in patients with stage I or II squamous cell carcinoma of the larynx, oral cavity, or pharynx who had been previously successfully treated with surgery, radiotherapy, or both, and whose diagnoses had been established within 36 months of study entry. As of September 16, 1999, the Retinoid Head and Neck Second Primary (HNSP) Trial had completed accrual with 1384 registered patients and 1191 patients randomized and eligible. All of the patients were followed for survival, SPT development, and index cancer recurrence. Smoking status was assessed at study entry and during study. Smoking cessation was confirmed biochemically by measurement of serum cotinine levels. The annual rate of SPT development was analyzed in terms of smoking status and tumor stage. As of May 1, 2000, SPTs have developed in 172 patients. Of these, 121 (70.3%) were tobacco-related SPTs, including 113 in the aerodigestive tract (57 lung SPTs, 50 HNSCC SPTs, and 6 esophageal SPTs) and 8 bladder SPTs. The remaining 51 cases included 23 prostate adenocarcinomas, 8 gastrointestinal malignancies, 6 breast cancers, 3 melanomas, and 11 other cancers. The annual rate of SPT development observed in our study has been 5.1%. SPT development related to smoking status was marginally significant (active versus never, 5.7% versus 3.5%; P = 0.053). Significantly different smoking-related SPT development rates were observed in current, former, and never smokers (annual rate = 4.2%, 3.2%, and 1.9%, respectively, overall P = 0.034; current versus never smokers, P = 0.018). Stage II HNSCC had a higher overall annual rate of SPT development (6.4%) than did stage I disease (4.3%; P = 0.004). When evaluating the development of smoking-related SPTs, stage was also highly significant (4.8% for stage II versus 2.7% for stage I; P = 0.001). Smoking-related SPT incidence was significant for site as well (larynx versus oral cavity, P = 0.015; larynx versus pharynx, P = 0.011). Primary tumors recurred at an annual rate of 2.8% in a total of 97 patients. The rate of recurrence was higher in patients with stage II disease (4.1% versus 2.2%, P = 0.004) as well as oral cavity site when compared with larynx (P = 0.002). This is the first large-scale prospective chemoprevention study evaluating smoking status and its impact on SPT development and recurrence rate in HNSCC. The results indicate significantly higher SPT rates in active smokers versus never smokers and significantly higher smoking-related SPT rates in active smokers versus never smokers, with intermediate rates for former smokers.

Adult↗

Prevalence of hepatitis B and C virus infection among women in Jeju Island, Republic of Korea.

Hepatitis B and C virus infection prevalence was investigated in the Island of Jeju (formerly Cheju), the Republic of Korea, by means of a small-scale sero-epidemiological survey in 2000. Adult women in the city of Jeju (the provincial capital) and two fishing-farming villages A and B were invited to offer venous blood samples for immunological examination for infection markers of two virus and serum biochemistry for liver function. In practice, 66 married women (33, 16 and 17 women from the city, Village A and Village B, respectively) volunteered. Sera were separated on site and were assayed for HBsAg, anti-HBs, anti-HBc, and anti-HCV positivities and liver function markers including AST, ALT and gamma-GTP. The serum assay showed that the prevalence of HbsAg+ or anti-HCV+ cases was low (5 and 2%, respectively), whereas that of anti-HBs+ and anti-HBc+ cases were high (71 and 62%) so that the over-all HBV positivity was 82%. There were essentially no urban-rural difference or age-dependent changes in the positivity. Comparison with the prevalence reported in literature shows that prevalence of HBsAg+ and anti-HCV+ is in general agreement with the values reported for the populations in general, but HBV+ prevalence might be somewhat higher than the levels reported for the general populations.

Adult↗

Early development of the secretory cavity of peltate glands in Humulus lupulus L. (Cannabaceae).

Early development of the secretory cavity of chemically fixed peltate glands in Humulus lupulus L. showed secretions with different densities, light, gray and dark, in the cytoplasm of disc cells and in the periplasmic space adjacent to the developing secretory cavity. Secretions were detected in the disc cell wall and subsequently in the developing secretory cavity under the subcuticular wall of the sheath. Light and gray secretions in the cavity possessed a membrane-like surface feature. Secretions were in contact with the irregular inner surface of the cuticle. Secretions contributed to the thickening of the cuticle, whereas the membrane-like surface feature contributed to a network of Cannabis striae distributed throughout the cuticle. This study supports an early development and organization of the secretory cavity in H. lupulus, parallel to those in Cannabis, and may represent common features for lipophilic glands in angiosperms.

Cannabis↗

Characterization of geranium (Pelargonium graveolens) chloroplast EF-Tu cDNA.

A geranium (Pelargonium graveolens) chloroplast translational elongation factor EF-Tu (tufA) cDNA was isolated. The geranium tufA cDNA is 1,584 bp long with 20 bp of 5' untranslated region (UTR) and 139 bp of 3' UTR. It encodes 474 amino acids including a putative chloroplast transit peptide of 65 amino acids. The deduced polypeptides of the geranium tufA cDNA contains four GTP binding sequences in its N-terminal region and two chloroplast EF-Tu signature regions in the C-terminal region. The predicted molecular weight of the mature geranium chloroplast EF-Tu protein was about 45,000 and its amino acid sequence identity with the chloroplast EF-Tu proteins of tobacco, pea, Arabidopsis, rice, and soybean ranges from 85% to 91%. The geranium tufA appears to exist as a single copy gene like Arabidopsis and rice, whereas other known dicot plants have more than one copy in their nuclear genomes.

Amino Acid Sequence↗

Arsenic trioxide-mediated growth inhibition in MC/CAR myeloma cells via cell cycle arrest in association with induction of cyclin-dependent kinase inhibitor, p21, and apoptosis.

We investigated the in vitro effect of As2O3 on proliferation, cell cycle regulation, and apoptosis in human myeloma cell lines. As2O3 significantly inhibited the proliferation of all of eight myeloma cell lines examined in a dose-dependent manner with IC50 of approximately 1-2 microM. DNA flow cytometric analysis indicated that As2O3 (2 microM) induced a G1 and/or a G2-M phase arrest in these cell lines. To address the mechanism of the antiproliferative effect of As2O3, we examined the effect of As2O3 on cell cycle-related proteins in MC/CAR cells in which both G1 and G2-M phases were arrested. Western blot analysis demonstrated that treatment with As2O3 (2 microM) for 72 h did not change the steady-state levels of CDK2, CDK4, cyclin D1, cyclin E, and cyclin B1 but decreased the levels of CDK6, cdc2, and cyclin A. The mRNA and protein levels of CDKI, p21 were increased by treatment with As2O3, but those of p27 were not. In addition, As2O3 markedly enhanced the binding of p21 with CDK6, cdc2, cyclin E, and cyclin A compared with untreated control cells. Furthermore, the activity of CDK6-associated kinase was reduced in association with hypophosphorylation of Rb protein. The activity of cdc2-associated kinase was decreased, which was accompanied by the up-regulation of cdc2 phosphorylation (cdc2-Tyr15 phosphorylation) resulting from reduction of cdc25B and cdc25C phosphatases. As2O3 also induced apoptosis in MC/CAR cells as evidenced by flow cytometric detection of sub-G1 DNA content and annexin V binding assay. This apoptotic process was associated with down-regulation of Bcl-2, loss of mitochondrial transmembrane potential (delta psi(m)), and an increase of caspase-3 activity. These results suggest that As2O3 inhibits the proliferation of myeloma cells, especially MC/CAR cells, via cell cycle arrest in association with induction of p21 and apoptosis.

Apoptosis↗

Spatial and temporal patterns of transneuronal labeling in CNS neurons after injection of pseudorabies virus into the sciatic nerve of adult rats.

The distribution of labeled neurons in the brain and spinal cord was studied after injecting the Bartha strain of pseudorabies virus (PRV) into the sciatic nerve to provide a baseline for studying neural circuitry after spinal cord injury (SCI) and regeneration. Following a single injection of viral particles into the left sciatic nerve, PRV labeling was found in the spinal cord at 2 days post-injection (p.i.). Increasing complexity in viral labeling from the spinal cord to supraspinal regions became apparent with increasing survival time. In brain regions, several neuronal groups that regulate sympathetic outflow, such as the rostroventrolateral medulla, the lateral paragigantocellular nuclei, and the A5 cells, were densely labeled. However, relatively sparse labeling was noticed in the lateral vestibular nuclei, the red nucleus and the motor cortex whose spinal projections regulate somatic motor function, although those areas were abundantly labeled with Fast blue (FB) in a double-labeling experiment in which FB was co-injected into the lumbar cord. The pattern of viral labeling became more complex beyond 5 days p.i. when increased numbers of cell groups were labeled with PRV but not FB. In addition, some infected neurons started to lyse, as evidenced by a decrease in viral labeling at 7 days p.i. Thus, the 5th day post-viral injection would appear to be an appropriate survival time to obtain maximal labeling with acceptable specificity. We suggest that transneuronal labeling using PRV should be appropriate for studying multi-neural circuitry after SCI and regeneration.

Amidines↗

Cell cycle arrest induced by the vitamin D(3) analog EB1089 in NCI-H929 myeloma cells is associated with induction of the cyclin-dependent kinase inhibitor p27.

EB1089, a 1,25-dihydroxyvitamin D(3) analog, has been known to have potent antiproliferative properties in a variety of malignant cells in vitro and in vivo. In the present study, we analyzed the effect of EB1089 on human myeloma cell lines. EB1089 inhibited the proliferation of NCI-H929 cells and RPMI8226 cells in a dose-dependent manner among three myeloma cell lines tested. The antiproliferative effect of EB1089 on myeloma cells was related to the expression level of vitamin D receptor. To investigate the mechanism of the antiproliferative effect of EB1089, cell cycle analysis was attempted in EB1089-sensitive NCI-H929 cells. EB1089 (1 x 10(-8) M) efficiently induced G(1) arrest of the cell cycle. Analysis of G(1) regulatory proteins demonstrated that protein levels of CDK2, CDK4, cyclin D1, and cyclin A were decreased in a time-dependent manner, but not those of CDK6 and cyclin E, by EB1089. In addition, EB1089 (1 x 10(-8) M, 72 h) increased the protein level of the CDKI p27 and markedly enhanced the binding of p27 with CDK2 compared to EB1089-untreated cells. Furthermore, the activity of CDK2-associated cyclin kinase was decreased, which was accompanied by the reduction of cyclin-D1-, cyclin-E-, and cyclin-A-associated kinase activities, resulting in the hypophosphorylation of Rb protein. These results suggest that EB1089 can inhibit the proliferation of human myeloma cells, especially NCI-H929 cells, via a G(1) block in association with the induction of p27 and the reduction of CDK2 activity.

Antineoplastic Agents↗

Phylogenetic analysis of the genera Pseudonocardia and Actinobispora based on 16S ribosomal DNA sequences.

The 16S rDNA sequences of 11 strains, nine type strains of validated Pseudonocardia species and Actinobispora yunnanensis, and two strains of unnamed Pseudonocardia species, were determined and compared with those of representatives of the family Pseudonocardiaceae. The phylogenetic analysis indicated that all of the validated species of the genera Pseudonocardia and Actinobispora consistently formed a monophyletic unit and separated well from the other genera of the family Pseudonocardiaceae. One unnamed Pseudonocardia strain was related to members of the genus Pseudonocardia, whereas the other unnamed Pseudonocardia strain formed a distinct clade within the radiation of the genus Amycolatopsis.

Actinomycetales↗

cDNA cloning and antibacterial activities of cecropin D-like peptides from Agrius convolvuli.

We have characterized full-length cDNAs encoding two isoforms of agriusin, cecropin D-like antibacterial peptide, present in the hemolymph of the immunized Agrius convolvuli larvae. The cloned cDNAs of agriusins 1 and 2 contain 331 and 329 bp, respectively. The nucleotide sequencing of cDNAs showed that they encode 62 amino acids, whose mature portion was deduced to consist of 38 amino acid residues with over 94% sequence identity. In the sequence homology search, mature agriusin 1 showed over 86 and 71% amino acid sequence homology with bactericidin 4 from Manduca sexta and cecropin D from Hyalophora cecropia, respectively. Since it was demonstrated from the deduced amino acid sequences that the C-terminal residues of agriusins are followed by a Gly residue, two types of synthetic agriusin 1 (syn-agriusin 1 amide and acid) were prepared to verify if natural agriusin 1 is C-terminally amidated. From acid-urea PAGE and reversed phase HPLC profiles to compare two synthetic peptides, we could confirm that the C-terminal amino acid residue of natural agriusin 1, like several cecropins so far identified, is amidated. Finally, our antibacterial assay performed with two syn-agriusins 1 revealed that there is little difference between antibacterial activities of both peptides against Gram-positive and Gram-negative bacteria.

Amino Acid Sequence↗

Taurine intake and excretion in patients undergoing long term enteral nutrition.

The purpose of this study was to investigate whether serum concentration and urinary excretion of taurine are influenced by marginal taurine intake. Twenty one male patients (75 to 95 years old), suffering from coronary heart disease, multiple cerebral infarction, cancer, subdural hematoma or respiratory failure were grouped according to duration of tube feeding (group one, 5.9 +/- 2.9; group two, 14.8 +/- 2.3; group three 48.0 +/- 22.7, mean +/- SD, months). The mean intake of taurine was 347.0 +/- 25.6, 339.8 +/- 25.6 and 337.1 +/- 259 micromol/day (mean +/- SEM) in group one, two and three, respectively. The fasting serum taurine levels were 106.5 +/- 9.6, 95.0 +/- 9.9 and 56.8 +/- 11.0 micromol/L (mean +/- SEM) in group one, two and three, respectively. Taurine level in group three patients was significantly lower than that of group one and two (p<0.05). The twenty-four hour urinary taurine excretion was 776.1 +/- 176.7, 782.4 +/- 245.3 and 388.3 +/- 169.3 micromol/day (mean +/- SEM) in group one, two and three, respectively. These results suggest that marginal taurine intake in patients receiving long term tube feeding could result in taurine deficiency.

Aged↗

Induction of apoptosis by vitamin D3 analogue EB1089 in NCI-H929 myeloma cells via activation of caspase 3 and p38 MAP kinase.

EB1089, a novel 1,25-dihydroxyvitamin D3 analogue, has been known to have potent antiproliferative properties in a variety of malignant cells both in vitro and in vivo. In the present study, we analysed the effect of EB1089 on NCI-H929 human myeloma cells. EB1089 inhibited cell growth of NCI-H929 and efficiently induced the G1 phase arrest of the cell cycle in a dose-dependent manner. We could also detect apoptosis in NCI-H929 cells exposed to EB1089 (1 x 10-7 M for 72 h) using the sub-G1 group of the cell cycle by FACS and annexin V binding assays. Induction of apoptosis by EB1089 was associated with down-regulation of the Bcl-2 protein without change of the Bax protein. Regarding caspase activity, which plays a crucial role in apoptosis, EB1089-treated NCI-H929 cells revealed an increased activity of caspase 3 protease accompanied by degradation of the PARP protein in a dose- and time-dependent manner. In addition, EB1089 caused the down-regulation of p44 extracellular signal-related kinase (ERK) activity and up-regulation of the p38 kinase activity during apoptosis of NCI-H929 cells. These results suggest that EB1089 inhibits growth of NCI-H929 cells via G1 cell cycle arrest as well as apoptosis by activating p38 kinase and suppressing ERK activity.

Antineoplastic Agents↗