• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.2
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• pp.39-44
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• 2023

Hereditary tyrosinemia type 1 (HT-1) is a metabolic disorder caused by biallelic pathogenic variants in the fumarylacetoacetate hydrolase (FAH) gene, which impairs the function of the FAH enzyme, resulting in the accumulation of tyrosine's toxic metabolites in hepatocytes and renal tubular cells. As a consequence, individuals with HT-1 exhibit symptomatic manifestations. Rapid diagnosis and treatment of HT-1 can prevent short-term death and long-term complications. A 15-day-old boy presented to the outpatient department with elevated levels of tyrosine on his newborn screening tests conducted at the age of 3 and 10 days, respectively. Further blood tests revealed increased levels of alpha-fetoprotein and amino acids including tyrosine and threonine. Urine organic acid tests indicated a significant elevation in tyrosine metabolites, as well as the presence of succinylacetone (SA), which led to the diagnosis of HT-1. Two pathogenic and likely pathogenic variants of FAH compatible with HT-1 were also detected. He began a tyrosine-restricted diet at one month old and received nitisinone (NTBC) at two months old. With continued treatment, the patient's initially elevated AFP level, detection of SA in the urine, and mild hepatomegaly showed improvement. During four years and seven months of treatment, there were no exceptional complications apart from an increase in tyrosine levels and a delay in speech. We report a case of tyrosinemia type 1 detected through newborn screening, treated with dietary restriction and NTBC, with a good prognosis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.2
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• pp.55-65
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• 2009

Purpose: We determined the therapeutic effects of blockade of epidermal growth factor(EGF) and vascular endothelial growth factor(VEGF) receptor tyrosine kinases on the growth of oral squamous cell carcinoma(OSCC) xenografted in athymic nude mice. Experimental Design: We investigated the in vivo antitumor effects of a tyrosine kinase inhibitor for EGFR and VEGFR-2, AEE788 in a mouth floor(orthotopic) tumor model. Nude mice with orthotopic tumors were randomized to receive AEE788, paclitaxel, a combination of AEE788 and paclitaxel, or control. Antitumor mechanisms of AEE788 were determined by immunohistochemical/immunofluorescent and apoptosis assays. Results: Tumors of mice treated with AEE788 demonstrated down-regulation of phosphorylated EGFR, phosphorylated VEGFR and their downstream mediators(pMAPK and pAkt), decreased proliferative index, decreased microvessel density(MVD). As a result, growth of the primary tumor and nodal metastatic potentials were inhibited by AEE788. Conclusion: These data show that EGFR and VEGFR can be molecular targets for the treatment of OSCC.

• Korean Journal of Veterinary Research
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• v.41 no.1
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• pp.13-19
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• 2001

A simple and rapid analytical method for the determination of tylosin in chicken, pork and muscle was established by High-Performance Liquid Chromatography(HPLC). Chicken, pork and beef muscle(5 g) were fortified by adding the $0.2{\mu}g/ml$ of standard tylosin and the drug was extracted from meats with 70% acetonitrile(ACN) and followed by liquid-liquid partition for clean-up procedure. Then $20{\mu}l$ portion of ACN elution was directly analyzed by HPLC with spectra 100 variable wavelength detector, and unfortified blank control were treated similarly. The average recovery rate of tylosin added to chicken, pork and beef muscle were $83{\pm}2.3$, $96{\pm}3.3$ and $92{\pm}1.6$(%) at the level 0.2 ppm, respectively. No tylosin residues in marketing meats. These results suggested that HPLC methodology could be acceptable for the extraction, determination and screening of tylosin residues in edible meats.

• Polymer(Korea)
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• v.28 no.4
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• pp.352-359
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• 2004

Membrane technology was used for the optical resolution of the various racemic compounds such as tryptophan, tyrosine and phenylalanine, using enantioselective membranes prepared from sodium alginate (SA) and glutaraldehyde as a membrane material and crosslinking agent, respectively, The chemical structure of the membranes was characterized with FT-IR spectrophotometry and 3D molecular structure modeling study was done to figure out the optical resolution mechanism through the membrane. Effects of degree of crosslinking, feed concentration, operating pressure and different kinds of feed solution on the membrane performances were studied. As results, it was found that with increasing degree of crosslinking and membrane thickness, and decrease in the concentration of the feed solution and smaller size of solutes, the enantinselectivity of the membrane was improved. When the sodium alginate membranes with 80% of swelling index and 79${\mu}{\textrm}{m}$ of thickness were used, 77% of enantiomeric excess was obtained.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.3
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• pp.193-201
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• 2006

Squamous cell carcinoma(SCC) of head and neck(SCCHN) is the sixth most common human malignant tumor. However, despite advances in prevention and treatment of SCC, the five-year survival rates for patients remain still low. To improve the outcome for patients with SCCHN, novel treatment strategies are needed. Overexpression of the epidermal growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.44-50
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• 2020

Background: Drug-drug interactions (DDIs) in patients using oral anticancer treatment are more common than in those using injectable anticancer agents. In addition, DDIs related to anticancer treatment are known to cause clinically significant outcomes, such as treatment failure and severe toxicity. To prevent these negative outcomes, significant DDIs are monitored and managed using the information provided in drug databases. We aimed to evaluate the consistency of information on clinically significant DDIs for tyrosine kinase inhibitors (TKIs) between representative drug databases. Methods: We selected clinically significant DDIs involving medications that are co-prescribed with TKIs and met the following criteria: the severity level of DDIs was equal or greater than "D" in Lexicomp^® or "major" in Micromedex^®. We then analyzed the consistency of the severity classification and evidence level between the drug databases. Spearman's correlation coefficient was used to identify the relationship between DDI information in the drug databases. Results: In total, 627 DDI pairs were identified as clinically significant; information on these was provided by Lexicomp^® and Micromedex^® for 571 and 438 pairs, respectively, and both drug databases provided information on 382 DDI pairs. There was no correlation between the severity and evidence level of DDIs provided in the two databases; Spearman's correlation coefficient for Lexicomp^® and Micromedex^® was -0.009 (p=0.861) and -0.064 (p=0.209), respectively. Conclusion: To judge the significance of DDIs, healthcare providers should consider that the information on DDIs may be different between drug information databases; hence, clinical factors must be considered concurrently.

• Analytical Science and Technology
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• v.14 no.5
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• pp.384-391
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• 2001

In this study, a new quantitative analytical method has been developed for the rapid determination of acylcarnitines and amino acids in human blood using electrospray ionization / tandem mass spectrometry (ESI-MS/MS). Acylarmitines and amino acids were analyzed by tandem mass spectrometry after conversion to their butylesters through treatment with 3N butanolic hydrogen chloride. Acylcrnitines were analyzed using precursor 85 ion scan and alanine, valine, leucine/isoleucine, methionine, phenylalanine, tyrosine, aspartic acid and glutamic acid were analyzed using neutral loss 102 scan, ornitine and citrulline were analyzed neutral loss 119 scan, glycine was analyzed using neutral loss 56 scan, arginine was analyzed using neutral loss 161 scan and argininosuccinic acid was analyzed product ion 459 scan. This method reduced sample preparation time compared to that with conventional amino acid analyzer and liquid chromatography, with high sensitivity and good reproducibility.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.5
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• pp.287-293
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• 2009

Cell survival is the result of a balance between programmed cell death and cellular proliferation. Cell membrane receptors and their associated signal transducing proteins control these processes. Of the numerous receptors and signaling proteins, epidermal growth factor receptor (EGFR) is one of the most important receptors involved in signaling pathways implicated in the proliferation and survival of cancer cells. EGFR is often highly expressed in human tumors including oral squamous cell carcinomas, and there is increasing evidence that high expression of EGFR is correlated with poor clinical outcome of common human cancers. Therefore, we examined the antiproliferative activity of gefitinib, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), in head and neck cancer cell lines. SCC-9, KB cells were cultured and growth inhibition activity of gefitinib was measured with MTT assay. To study influence of gefitinib in cell cycle, we performed cell cycle analysis with flow cytometry. Western blot was done to elucidate the expression of EGFR in cell lines and phosphorylation of EGFR and downstream kinase protein, Erk and Akt. Significant growth inhibition was observed in SCC-9 cells in contrast with KB cells. Also, flow cytometric analysis showed G1 phase arrest only in SCC-9 cells. In Western blot analysis for investigation of EGFR expression and downstream molecule phosphorylation, gefitinib suppressed phosphorylation of EGFR and downstream protein kinase Erk, Akt in SCC-9. However, in EGFR positive KB cells, weak expression of active form of Erk and Akt and no inhibitory activity of phosphorylation in Erk and Akt was observed. The antiproliferative activity of gefitinib was not correlated with EGFR expression and some possibility of phosphorylation of Erk and Akt as a predictive factor of gefitinib response was emerged. Further investigations on more reliable predictive factor indicating gefitinib response are awaited to be useful gefitinib treatment in head and neck cancer patients.

• KSBB Journal
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• v.24 no.5
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• pp.458-462
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• 2009

Silk fibroin is a structural protein from Bombyx mori and can be sulfated to provide biofunctional polypeptides showing antiviral and anticoagulating activities. However, the sulfated fibroins have not been characterized enough to present their compositions and structures. In this report, sulfation reaction was investigated by varying the reaction temperature and sulfuric acid concentration and analysis of the resulting peptides were carried out. The degree of sulfation was proportion to sulfuric acid concentration but the maximum product yield was obtained at $60^{\circ}C$ and 5% of sulfuric acid concentration. FT-IR spectrum, UV absorption and NMR spectrum support that o-sulfate ester was formed at the hydroxyl group of serine and tyrosine residues. Size exclusion chromatography identified that sulfated fibroin was composed of a highly hydrolyzed polypeptide mixtures and peptides of relatively higher molecular weight.

• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.158-164
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• 2005

Purpose: The serine/threonine kinase Akt was described to inhibit apoptosis in cancer. This study was to examine the effect of Gleevec on head and neck squamous cell carcinoma(HNSCC) through the mechanism of Akt. Experimental Design: Gleevec was introduced into the HNSCC cell lines UMSCC10B, HN12 and HN30 in a range of concentrations. Cell viability was assessed by clonogenic survival analysis. Targets of Gleevec(PDGFR, c-Kit, and c-Abl) were evaluated by Western blot. HNSCC tissue samples were stained for PDGFR, c-Kit and phosphorylated Akt. Akt phosphorylation following Gleevec treatment was assessed using Western blot. Akt siRNA was used to as the positive control. Results: Colony forming efficiency decreased with an increase in concentration of Gleevec. Expressions of PDGFR, c-Kit, and c-Abl were observed in HNSCC cells. Immunohistochemistry confirmed high expression of PDGFR, c-Kit, and p-Akt in human HNSCC tissues. Akt kinase activity was significantly inhibited with increasing concentration of Gleevec in HNSCC cells, and near complete dephosphorylation of Akt was observed at $6{\mu}M$ of Gleevec in the UMSCC10B and HN30 cell lines. Conclusions: Gleevec at clinically comparable concentrations caused a dose dependant decrease in HNSCC survival. The decreased cell survival was related to the inhibition of Akt kinase activity and dephosphorylation of Akt. Akt signaling pathway may be a relevant target for Gleevec in treating HNSCC.