• BMB Reports
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• v.41 no.4
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• pp.278-286
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• 2008

Angiogenesis, the formation of blood vessels, is essential for preparing a closed circulatory system in the body, and for supplying oxygen and nutrition to tissues. Major diseases such as cancer, rheumatoid arthritis, and atherosclerosis include pathological angiogenesis in their malignant processes, suggesting anti-angiogenic therapy to be a new strategy for suppression of diseases. However, until the 1970s, the molecular basis of angiogenesis was largely unknown. In recent decades, extensive studies have revealed a variety of angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)-VEGFRs, Angiopoietin-Tie, Ephrin-EphRs and Delta-Notch to be the major regulators of angiogenesis in vertebrates. VEGF and its receptors play a central role in physiological as well as pathological angiogenesis, and functional inhibitors of VEGF and VEGFRs such as anti-VEGF neutralizing antibody and small molecules that block the tyrosine kinase activity of VEGFRs have recently been approved for use to treat patients with colorectal, lung, renal and liver cancers. These drugs have opened a novel field of cancer therapy, i.e. anti-angiogenesis therapy. However, as yet they cannot completely cure patients, and cancer cells could become resistant to these drugs. Thus, it is important to understand further the molecular mechanisms underlying not only VEGF-VEGFR signaling but also the VEGF-independent regulation of angiogenesis, and to learn how to improve anti-angiogenesis therapy.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.sup1
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• pp.46-51
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• 2008

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasm of the gastrointestinal tract, and can be distinguished from the smooth muscle or neural tumors in approximately 95% of patients by expression of the KIT receptor tyrosine kinase (CD117). GISTs are known to have high malignant potential and none can be labeled definitely as benign. However, GISTs are unresponsive to standard sarcoma chemotherapy, and only complete surgical resection provides chance for cure. Although the imaging modality of choice is enhanced CT scan in patients with GIST, FDG PET can reflect the malignant potential of GIST. Clinical management of patients with GISTs has dramatically changed with the introduction of novel therapeutics, such as imatinib mesylate (Glivec). This has created a need to re-evaluate the existing criteria used to assess treatment response. FDG PET as functional imaging modality proved to be significantly more accurate than CT alone when assessing GIST response to imatinib. And, FDG PET and PET ICT have been found to be highly sensitive in detecting early response, and to be useful in predicting long-term response to imatinib in patients with recurrent or metastatic GISTs.

• Development and Reproduction
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• v.20 no.2
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• pp.149-155
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• 2016

Sprouty (Spry) genes encode inhibitors of the receptor tyrosine kinase signaling cascade, which plays important roles in stem cells. However, the role of Spry4 in the stemness of embryonic stem cells has not been fully elucidated. Here, we used mouse embryonic stem cells (mESCs) as a model system to investigate the role of Spry4 in the stem cells. Suppression of Spry4 expression results in the decreases of cell proliferation, EB formation and stemness marker expression, suggesting that Spry4 activity is associated with stemness of mESCs. Teratoma assay showed that the cartilage maturation was facilitated in Spry4 knocked down mESCs. Our results suggest that Spry4 is an important regulator of the stemness and differentiation of mESCs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2235-2240
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• 2012

c-Src is one member of non-receptor tyrosine kinase protein family that has over expression and activation in many human cancer cells. It has been shown that c-Src is implicated in various downstream signaling pathways associated with EGFR-dependent signaling such as MAPK and STAT5 pathways. Transactivation of EGFR by c-Src is more effective than EGFR ligands. To inhibit the c-Src expression, we used c-Src antisense oligonucleotide complexed with PAMAM Denderimes. The effect of c-Src antisense oligonucleotide on HT29 cell proliferation was determined by MTT assay. Then, the expression of c-Src, EGFR and the genes related to EGFR-depended signaling with P53 was applied by real time PCR. We used western blot analysis to elucidate the effect of antisense on the level of c-Src protein expression. The results showed, c-Src antisense complexed with PAMAM denderimers has an effective role in decrease of c-Src expression and EGFR-dependent downstream genes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.691-694
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• 2013

Purpose: By carrying out a meta-analysis of randomized controlled trials that compared sorafenib or combined chemotherapy with placebo or combined chemotherapy, the effectiveness of sorafenib in hepatocellular carcinoma was evaluated in the present study, which also provided clinical practice guidelines of evidence-based-medicine. Methods: We reviewed PubMed citations concerning sorafenib treating hepatocellular carcinoma in randomized controlled trials from Jan 2000 to July 2012. All the literature was extracted by Cochrane systematic reviews and underwent meta-analysis with RewMan 5.0 software. Results: Finally, four papers documenting randomized controlled studies were included. Compared with controls, sorafenib was shown to significantly increase overall survival (OS), time to progression (TTP), and disease control rates (DCR), but not the time to symptom progression (TTSP) in hepatocellular carcinoma patients. The incidence of grade-III/IV adverse reactions, including hand-foot-skin reactions, diarrhea, hypertension and skin rash or desquamation, in sorafenib treatment group was higher than that in controls. However, there was no significant difference in the incidence of hypodynamia between the two groups. Conclusions: Sorafenib exerts significant curative effects in hepatocellular carcinoma.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.14-23
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• 2002

Development of oligodendrocytes and the generation of myelin internodes within the spinal cord depends on regional signals derived from the notochord and axonally derived signals. Neuregulin (NRG)-1, localized in the floor plate as well as in motor and sensory neurons, is necessary for normal oligodendrocyte development. Oligodendrocytes respond to NRGs by activating members of the erbB receptor tyrosine kinase family. Here, we show that erbB2 is not necessary for the early stages of oligodendrocyte precursor development, but is essential for proligodendroblasts to differentiate into galactosylcerebroside-positive (GalC+) oligodendrocytes. In the presence of erbB2, oligodendrocyte development is normal. In the absence of erbB2 (erbB2-/-), however, oligodendrocyte development is halted at the proligodendroblast stage with a >10-fold reduction in the number of GalC+ oligodendrocytes. ErbB2 appears to function in the transition of proligodendroblast to oligodendrocyte by transducing a terminal differentiation signal, since there is no evidence of increased oligodendrocyte death in the absence of erbB2. Furthermore, known survival signals for oligodendrocytes increase oligodendrocyte numbers in the presence of erbB2, but fail to do so in the absence of erbB2. Of the erbB2-/- oligodendrocytes that do differentiate, all fail to ensheath neurites. These data suggest that erbB2 is required for the terminal differentiation of oligodendrocytes and for development of myelin.

• Tuberculosis and Respiratory Diseases
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• v.62 no.2
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• pp.144-148
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• 2007

Gefitinib is an oral selective inhibitor that targets the tyrosine kinase of the epidermal growth factor receptor. The prevalence of interstitial lung disease is 2% in Japan and 0.3% in the USA with a mortality rate of up to one third. We describe two non-small cell lung cancer patients who developed acute respiratory failure after gefitinib, and suggest that clinicians take extreme caution when deciding to treat patients with gefitinib.

• Molecules and Cells
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• v.38 no.1
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• pp.14-19
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• 2015

Eph receptors and their ligands, ephrins, represent the largest group of the receptor tyrosine kinase (RTK) family, and they mediate numerous developmental processes in a variety of organisms. Ephrins are membrane-bound proteins that are mainly divided into two classes: A class ephrins, which are linked to the membrane by a glycosylphosphatidylinositol (GPI) linkage, and B class ephrins, which are transmembrane ligands. Based on their domain structures and affinities for ligand binding, the Eph receptors are also divided into two groups. Trans-dimerization of Eph receptors with their membrane-tethered ligands regulates cell-cell interactions and initiates bidirectional signaling pathways. These pathways are intimately involved in regulating cytoskeleton dynamics, cell migration, and alterations in cellular dynamics and shapes. The EphBs and ephrinBs are specifically localized and modified to promote higher-order clustering and initiate of bidirectional signaling. In this review, we present an in-depth overview of the structure, mechanisms, cell signaling, and functions of EphB/ephrinB in cell adhesion and migration.

• Journal of Clinical Otolaryngology Head and Neck Surgery
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• v.29 no.2
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• pp.290-294
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• 2018

Mammary analogue secretory carcinoma (MASC) has histologic similarities to not only acinic cell carcinoma but also other low grade cystadenocarcinoma, and has similar features to breast secretory carcinoma. MASC was not described through the existing classification system previously. But, MASC was distinguished from other salivary gland tumors by Skalova et al. in 2010, MASC has ets variant gene 6-neurotrophic tyrosine kinase, receptor, type 3 (ETV6-NTRK3) translocation. So far, there are 4 cases of MASC recognized in the head and neck region in Korea. One of the four is a tumor from the submandibular gland, and the other three are of the parotid gland. In this case report, we report a 40-year-old man with a MASC of the parotid gland, who presented with right infra-auricular mass.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.1-20
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• 2019

Neuropathic pain is a complex chronic pain state caused by the dysfunction of somatosensory nervous system, and it affects the millions of people worldwide. At present, there are very few medical treatments available for neuropathic pain management and the intolerable side effects of medications may further worsen the symptoms. Despite the presence of profound knowledge that delineates the pathophysiology and mechanisms leading to neuropathic pain, the unmet clinical needs demand more research in this field that would ultimately assist to ameliorate the pain conditions. Efforts are being made globally to explore and understand the basic molecular mechanisms responsible for somatosensory dysfunction in preclinical pain models. The present review highlights some of the novel molecular targets like D-amino acid oxidase, endoplasmic reticulum stress receptors, sigma receptors, hyperpolarization-activated cyclic nucleotide-gated cation channels, histone deacetylase, $Wnt/{\beta}-catenin$ and Wnt/Ryk, ephrins and Eph receptor tyrosine kinase, Cdh-1 and mitochondrial ATPase that are implicated in the induction of neuropathic pain. Studies conducted on the different animal models and observed results have been summarized with an aim to facilitate the efforts made in the drug discovery. The diligent analysis and exploitation of these targets may help in the identification of some promising therapies that can better manage neuropathic pain and improve the health of patients.