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Mitotic protein kinase-driven crosstalk of machineries for mitosis and metastasis
Kim Chang-Hyeon,Kim Da-Eun,Kim Dae-Hoon,Min Ga-Hong,Park Jung-Won,Kim Yeo-Bin,Sung Chang K.,Yim Hyungshin 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Accumulating evidence indicates that mitotic protein kinases are involved in metastatic migration as well as tumorigenesis. Protein kinases and cytoskeletal proteins play a role in the efficient release of metastatic cells from a tumor mass in the tumor microenvironment, in addition to playing roles in mitosis. Mitotic protein kinases, including Polo-like kinase 1 (PLK1) and Aurora kinases, have been shown to be involved in metastasis in addition to cell proliferation and tumorigenesis, depending on the phosphorylation status and cellular context. Although the genetic programs underlying mitosis and metastasis are different, the same protein kinases and cytoskeletal proteins can participate in both mitosis and cell migration/invasion, resulting in migratory tumors. Cytoskeletal remodeling supports several cellular events, including cell division, movement, and migration. Thus, understanding the contributions of cytoskeletal proteins to the processes of cell division and metastatic motility is crucial for developing efficient therapeutic tools to treat cancer metastases. Here, we identify mitotic kinases that function in cancer metastasis as well as tumorigenesis. Several mitotic kinases, namely, PLK1, Aurora kinases, Rho-associated protein kinase 1, and integrin-linked kinase, are considered in this review, as an understanding of the shared machineries between mitosis and metastasis could be helpful for developing new strategies to treat cancer.
Kim, Da-Yeon,Kim, Tae-Ho,Kim, Jung-Bin The Korean Society of Physical Therapy 2017 대한물리치료학회지 Vol.27 No.6
Purpose: The aim of this study was to investigate if the 7-item Berg balance scale (BBS) 3-point, which is a short form of the BBS (SFBBS), has compatible psychometric properties in comparison with the original BBS, and also to study the concurrent validity using a 10-meter walk test (10mWT) and a timed up and go test (TUG), which are widely used with SFBBS in clinical settings. Methods: A total of 255 patients who had experienced stroke participated in this cross-sectional study. We used results obtained from 188 patients who completed both 10mWT and TUG. The three levels in the center of the BBS were collapsed to a single level (i.e.,0-2-4) to form the SFBBS. The concurrent validity was assessed by computing the Spearman coefficients for correlation among outcome measures and in between each outcome measure and the SFBBS. As there were four outcomes, the corrected p-value for significant correlation was 0.013 (0.05/4). Results: Spearman coefficients for correlations and evaluation instruments for concurrent validity revealed significantly high validity for both of SFBBS and BBS (r=0.944). 10mWT and TUG were -0.749 and -0.770 respectively, which are in the high margin and are statistically significant (p>0.000). Conclusion: SFBBS has sound psychometric properties for evaluating patients with stroke. Thus, we recommend the use of SFBBS in both clinical and research settings.
Kim, Jin Han,Jeong, Hui Rak,Jung, Da Woon,Yoon, Hong Bin,Kim, Sun Young,Kim, Hyoung Ja,Lee, Kyung-Tae,Gadotti, Vinicius M.,Huang, Junting,Zhang, Fang-Xiong,Zamponi, Gerald W.,Lee, Jae Yeol Pergamon 2017 Bioorganic & medicinal chemistry Vol.25 No.17
<P><B>Abstract</B></P> <P>As a bioisosteric strategy to overcome the poor metabolic stability of lead compound KYS05090S, a series of new fluoro-substituted 3,4-dihydroquinazoline derivatives was prepared and evaluated for T-type calcium channel (Ca<SUB>v</SUB>3.2) block, cytotoxic effects and liver microsomal stability. Among them, compound <B>8h</B> (KCP10068F) containing 4-fluorobenzyl amide and 4-cyclohexylphenyl ring potently blocked Ca<SUB>v</SUB>3.2 currents (>90% inhibition) at 10μM concentration and exhibited cytotoxic effect (IC<SUB>50</SUB> =5.9μM) in A549 non-small cell lung cancer cells that was comparable to KYS05090S. Furthermore, <B>8h</B> showed approximately a 2-fold increase in liver metabolic stability in rat and human species compared to KYS05090S. Based on these overall results, <B>8h</B> (KCP10068F) may therefore represent a good backup compound for KYS05090S for further biological investigations as novel cytotoxic agent. In addition, compound <B>8g</B> (KCP10067F) was found to partially protect from inflammatory pain via a blockade of Ca<SUB>v</SUB>3.2 channels.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Circulating Levels of Adipokines Predict the Occurrence of Acute Graft-versus-host Disease
Kim, Jin Sook,You, Da-Bin,Lim, Ji-Young,Lee, Sung-Eun,Kim, Yoo-Jin,Kim, Hee-Je,Chung, Nack-Gyun,Min, Chang-Ki The Korean Association of Immunobiologists 2015 Immune Network Vol.15 No.2
Currently, detecting biochemical differences before and after allogeneic stem cell transplantation (SCT) for improved prediction of acute graft-versus-host disease (aGVHD) is a major clinical challenge. In this pilot study, we analyzed the kinetics of circulating adipokine levels in patients with or without aGVHD before and after allogeneic SCT. Serum samples were obtained and stored at $-80^{\circ}C$ within 3 hours after collection, prior to conditioning and at engraftment after transplantation. A protein array system was used to measure the levels of 7 adipokines of patients with aGVHD (n=20) and without aGVHD (n=20). The resistin level at engraftment was significantly increased (p<0.001) after transplantation, regardless of aGVHD occurrence. In the non-aGVHD group, the concentrations of the hepatocyte growth factor (HGF) (mean values${\pm}$SD; $206.6{\pm}34.3$ vs. $432.3{\pm}108.9pg/ml$, p=0.040) and angiopoietin-2 (ANG-2) (mean values${\pm}$SD; $3,197.2{\pm}328.3$ vs. $4,471.8{\pm}568.4pg/ml$, p=0.037) at engraftment were significantly higher than those of the pre-transplant period, whereas in the aGVHD group, the levels of adipokines did not change after transplantation. Our study suggests that changes in serum HGF and ANG-2 levels could be considered helpful markers for the subsequent occurrence of aGVHD.