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Identification of novel ALK2 inhibitors and their effect on cancer cells
Kim, Minsung,Choi, Okran,Pyo, Suhkneung,Choi, Sang Un,Park, Chi Hoon Elsevier 2017 Biochemical and biophysical research communication Vol.492 No.1
<P><B>Abstract</B></P> <P>Bone morphogenetic protein 9 (BMP9), a member of the TGF-β superfamily, is considered a regulator of glucose homeostasis as well as a neuronal differentiation factor. BMP9 induces phosphorylation of Smad1/5 through activin receptor-like kinase 1 and 2 (ALK1 and ALK2). Recently, many studies have shown that BMP9 contributes to tumorigenesis, and aberrant ALK2 expression is involved in many diseases. To investigate the role of BMP9-ALK2 signaling in cancer cells, we used TF-1 cells that require granulocyte-macrophage colony-stimulating factor (GM-CSF) for cell proliferation. BMP9 promoted the proliferation of TF-1 cells in media lacking GM-CSF. TF-1 cells overexpressing ALK2 resulted in the autophosphorylation of Smad1/5, leading to consequent increase in cell growth. Through high-throughput screening (HTS), we found two ALK2-specific inhibitors, KRC203 and KRC360, with IC<SUB>50</SUB> values of 0.9 nM and 0.3 nM. These compounds were more potent and specific for the inhibition of ALK2 when compared to LDN193189. In cell-based assays, these compounds effectively inhibited the proliferation and migration of cancer cells induced by ALK2 and BMP9. Therefore, we propose that our compounds are promising candidates for the treatment of cancer or diseases with abnormal ALK2 or BMP9 signaling.</P> <P><B>Highlights</B></P> <P> <UL> <LI> BMP9 signaling promoted the proliferation of cancer cells via Smad1/5 pathway. </LI> <LI> Overexpressing ALK2, a BMP9 receptors, promoted the proliferation of cancer cells. </LI> <LI> KRC203 and KRC360 that we found through high-throughput screening showed high specific inhibition against ALK2. </LI> <LI> Our compounds inhibited specificity BMP9 signaling and inhibited the migration of hepatocellular carcinoma. </LI> <LI> Our compounds also effectively inhibited the proliferation of cancer cells by BMP9 and ALK2 signaling. </LI> </UL> </P>
Heonju Ha,이재범,Okran Lee,Gon Hwang,Seuran Park,HyeokJa Kwon,Songsim Kim J-INSTITUTE 2020 International Journal of Crisis & Safety Vol.5 No.2
Purpose: This study conducted the exploration using the Colaizzi method, a phenomenological research meth-od to identify the constituents of the experience of the SNB-program, one of Terahertz therapy, which is receiving much attention as a thermal treatment method recently. Method: The data collection method of the first study using the Colaizzi method consisted of literature review for theoretical extraction, narrative observation and interview. For the first analysis of the data, the Colaizzi 6-step analysis method, a phenomenological research method, was used to identify the participants' SNB-program expe-rience and explore the constituent factors of the human body's natural healing experience. Second, a question-naire was created based on the constituent factors of the participant's experience identified through in-depth in-terviews, and the principle component analysis of 123 questionnaires collected was conducted to verify the inner validity of the research results. Results: In the results of this study, the SNB-program experience was confirmed based on two categories such as positive experience and uncomfortable experience. In detail, eight types of uncomfortable experiences includ-ing eight physical changes, six emotional changes, five social education changes, and improvements were derived. In addition, to verify the validity and reliability of the extracted constituent factors, from the results of constructing preliminary items and conducting exploratory factor analysis, lastly, it was confirmed with two categories, five theme clusters, and 27 formulated meanings. Conclusion: In this study, the SNB-program participant's experience was verified in vivid language through the Colaizzi method, and the procedure was verified through social science analysis. The results of this study are meaningful in that the user's experience of thermotherapy using Terahertz waves has been generalized.
Der Sheng Sun,Hye Sung Won,Soon Auck Hong,Ji Hyung Hong,Heejoon Jo,Heejin Lee,Okran Kim,Myung Ah Lee,Yoon Ho Ko 대한내과학회 2020 The Korean Journal of Internal Medicine Vol.35 No.2
Background/Aims: Hyaluronic acid (HA) regulates cell adhesion, migration and proliferation in various cancers. The clinical implications of HA in resected head and neck squamous cell carcinoma have not been elucidated. We investigated the clinical significance and prognostic value of the expression of tumoral and stromal HA and its related proteins in oropharyngeal and oral cavity cancer. Methods: Resected tissues from oropharyngeal or oral cavity cancer patients undergoing surgery were analysed in tissue microarrays divided into stroma and cancer panels. The expression levels of HA, HA synthases and hyaluronidases were also assessed by immunohistochemistry. Results: A total of 160 resected oropharyngeal or oral cavity cancer tissues were analysed. Stromal HA expression was observed more frequently in human papilloma virus (HPV)-negative tumors, but other clinicopathological characteristics did not differ. In patients with HPV-negative oral cavity cancers, high stromal HA expression was associated with significantly shorter recurrence-free survival and overall survival compared with low stromal HA expression. The expression of HA in both tumors and stroma was significantly correlated with poorer outcomes than other combinations in patients with HPV-negative oral cavity cancers. However, these prognostic roles of HA were not observed in patients with HPV-negative oropharyngeal cancers. In the HPV-stratified multivariate analysis, high stromal HA expression remained an independent indicator of poor prognosis in terms of recurrence-free survival. Conclusions: High stromal HA and expression of HA in both tumors and stroma were correlated with poor prognosis in HPV-negative oral cavity cancer, but not in HPV-negative oropharyngeal cancers.