• BMB Reports
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• 제53권5호
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• pp.254-259
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• 2020

Increasing evidence suggests the role of miR-449a in the regulation of tumorigenesis and autophagy. Autophagy plays an important role in the malignancy of T-cell lymphoma. However, it is still unknown whether miR-449a is associated with autophagy to regulate the malignancy of T-cell lymp homa. In this study, we for the first time demonstrated that miR-449a enhanced apoptosis of T-cell lymphoma cells by decreasing the degree of autophagy. Further, miR-449a downregulated autophagy-associated 4B (ATG4B) expression, which subsequently reduced the autophagy of T-cell lymphoma cells. Mechanistically, miR-449a decreased ATG4B protein level by binding to its mRNA 3'UTR, thus reducing the mRNA stability. In addition, studies with nude mice showed that miR-449a significantly inhibited lymphoma characteristics in vivo. In conclusion, our results demonstrated that the "miR-449a/ATG4B/autophagy" pathway played a vital role in the malignancy of T-cell lymphoma, suggesting a novel therapeutic target.

• BMB Reports
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• 제55권5호
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• pp.244-249
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• 2022

Characterized by abnormal proliferation and migration of vascular smooth muscle cells (VSMCs), neointima hyperplasia is a hallmark of vascular restenosis after percutaneous vascular interventions. Vaccinia-related kinase 1 (VRK1) is a stress adaption-associated ser/thr protein kinase that can induce the proliferation of various types of cells. However, the role of VRK1 in the proliferation and migration of VSMCs and neointima hyperplasia after vascular injury remains unknown. We observed increased expression of VRK1 in VSMCs subjected to platelet-derived growth factor (PDGF)-BB by western blotting. Silencing VRK1 by shVrk1 reduced the number of Ki-67-positive VSMCs and attenuated the migration of VSMCs. Mechanistically, we found that relative expression levels of β-catenin and effectors of mTOR complex 1 (mTORC1) such as phospho (p)-mammalian target of rapamycin (mTOR), p-S6, and p-4EBP1 were decreased after silencing VRK1. Restoration of β-catenin expression by SKL2001 and re-activation of mTORC1 by Tuberous sclerosis 1 siRNA (siTsc1) both abolished shVrk1-mediated inhibitory effect on VSMC proliferation and migration. siTsc1 also rescued the reduced expression of β-catenin caused by VRK1 inhibition. Furthermore, mTORC1 re-activation failed to recover the attenuated proliferation and migration of VSMC resulting from shVrk1 after silencing β-catenin. We also found that the vascular expression of VRK1 was increased after injury. VRK1 inactivation in vivo inhibited vascular injury-induced neointima hyperplasia in a β-catenin-dependent manner. These results demonstrate that inhibition of VRK1 can suppress the proliferation and migration of VSMC and neointima hyperplasia after vascular injury via mTORC1/β-catenin pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10855-10860
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• 2015

Background: The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma ${\beta}$-endorphin levels in cancer patients. Materials and Methods: A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma ${\beta}$-endorphin levels were measured by radioimmunoassay. Results: With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma ${\beta}$-endorphin levels. After the treatment, plasma ${\beta}$-endorphin level in group B was $62.4{\pm}13.5pg/ml$, which was higher than that in group A ($45.8{\pm}11.2pg/ml$) (p<0.05). Conclusions: Our results suggest the combination of intravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma ${\beta}$-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.

• 한국방재안전학회논문집
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• 제6권1호
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• pp.47-53
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• 2013

우리나라의 표준현장지휘체계는 긴급구조통제단 가동 시 소방기관이 지휘권자가 되는 긴급구조 활동에만 국한되어 있는 재난현장 대응편제체계이다. 그러나 풍수해, 산사태 등 재난 발생 시 많은 일반직 공무원들도 재난현장에서 대응활동과 수습활동을 수행하나 이들을 위한 재난현장 대응편제체계는 없는 실정이다. 따라서 재난현장에서 일반직 공무원들과 유관기관들 간에 신속하고도 단절됨이 없이 협력적으로 대응과 수습활동을 하도록 하기 위하여 기관 간 협력 필요업무를 도출하였으며, 이를 토대로 재난현장 대응편제체계 개발 시 고려해야 할 사항에 대하여 제시하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3831-3836
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• 2013

Background: S100A14 has recently been implicated in the progress of several types of cancers. This study aimed to investigate the clinical significance and possible mechanisms of action of S100A14 in the invasion and metastasis of hepatocellular carcinoma (HCC). Methods: S100A14 expression in HCC was detected at mRNA and protein levels and its prognostic significance was assessed. Functional roles of S100A14 in HCC were investigated using MTT, BrdU, wound healing, transwell invasion assay and HCC metastatic mouse model. Results: S100A14 was significantly elevated in HCC tissues, correlated with multiple tumor nodes, high Edmondson-Steiner grade and vascular invasion. Multivariate Cox analysis showed that the S100A14 expression level was a significant and independent prognostic factor for overall survival (OS) of HCC patients (hazard ratio=1.98, 95% confidence interval=1.14-3.46, P=0.013). S100A14 promoted cell proliferation, invasion and metastasis of HCC in vitro and in vivo. Conclusion: These results suggest S100A14 is a novel prognostic marker and therapeutic target for HCC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8331-8335
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• 2014

Background: Previous studies accessing the association of CYP2C19 with outcomes of patients using tamoxifen for breast cancer have yielded conflicting results. The aim of this meta-analysis is to obtain a more precise estimate of effects of CYP2C19 polymorphisms and to clarify their effects on survival of the breast cancer patients using tamoxifen. Materials and Methods: A systematic search of PubMed and Embase was performed, comparing patients with or without $CYP2C19^*2$ and $CYP2C19^*17$, relevant articles searched for. The following outcomes were included from the eligible studies: disease-free survival (DFS) and overall survival (OS), expressed by hazard ratios (HR) with corresponding 95% confidence interval (CI). Subgroup analysis by genotypes was also performed. Pooled estimates were calculated using random-effect model in accordance to the heterogeneity. Results: Six studies met the inclusion criteria. The integrated OR on the association between CYP2C19 and DFS, calculated by the random-effect model, was 0.54 (95%CI=0.34-0.84, p=0.013). Subgroup analysis showed that both $CYP2C19^*2$ and $CYP2C19^*17$ were associated with increased survival. The pooled results of two studies for OS were OR=0.46 (95%CI=0.21-1.01, p=0.233). Conclusions: This meta-analysis suggests that the $CYP2C19^*2$ and $CYP2C19^*17$ genotypes are associated with increased survival in breast cancer patients using tamoxifen.

• BMB Reports
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• 제53권3호
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• pp.154-159
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• 2020

We investigated the effects of physalin A, B, D, and F on osteoclastogenesis induced by receptor activator of nuclear factor κB ligand (RANKL). The biological functions of different physalins were first predicted using an in silico bioinformatic tool (BATMAN-TCM). Afterwards, we tested cell viability and cell apoptosis rate to analyze the cytotoxicity of different physalins. We analyzed the inhibitory effects of physalins on RANKL-induced osteoclastogenesis from mouse bone-marrow macrophages (BMMs) using a tartrate-resistant acid phosphatase (TRAP) stain. We found that physalin D has the best selectivity index (SI) among all analyzed physalins. We then confirmed the inhibitory effects of physalin D on osteoclast maturation and function by immunostaining of F-actin and a pit-formation assay. On the molecular level, physalin D attenuated RANKL-evoked intracellular calcium ([Ca(2+)](i)) oscillation by inhibiting phosphorylation of phospholipase Cγ2 (PLCγ2) and thus blocked the downstream activation of Ca2+/calmodulin-dependent protein kinases (CaMK)IV and cAMP-responsive element-binding protein (CREB). An animal study showed that physalin D treatment rescues bone microarchitecture, prevents bone loss, and restores bone strength in a model of rapid bone loss induced by soluble RANKL. Taken together, these results suggest that physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via suppressing the PLCγ2-CaMK-CREB pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1349-1353
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• 2012

Increasing evidence has revealed that thy-1 was a potential stem cell marker of liver cancer, but no data have been shown on how thy-1 regulates the pathophysiology of liver cancer, such as proliferation, apoptosis, invasion and migration. We previously demonstrated that thy-1 was expressed in about 1% of hepg2 cells, thy-1+hepg2 cells, but not thy-1-, demonstrating high tumorigenesis on inoculation $0.5{\times}10^5$ cells per BACA/LA mouse after 2 months. In the present study, our results showed that higher expression of thy-1 occurs in 72% (36/50 cases) of neoplastic hepatic tissues as compared to 40% (20/50 cases) of control tissues, and the expression of thy-1 is higher in poorly differentiated liver tumors than in the well-differentiated ones. In addition, thy-1 expression was detected in 85% of blood samples from liver cancer patients, but none in normal subjects or patients with cirrhosis or hepatitis. There was a significant negative correlation between thy-1expression and E-cadherin expression (a marker of invasion and migraton), but not between thy-1 expression and AFP expression in all the liver cancer and blood samples. We further investigated the relationship between thy-1 and E-cadherin in liver cancer hepg2 cell line which was transfected with pReceiver-M29/thy-1 eukaryotic expression vector followed by aspirin treatment. Lower expression of E-cadherin but higher expressions of thy-1 were detected in hepg2 cells transfected with pReceiver-M29/thy-1. Taken together, our study suggested that thy-1 probably regulates liver cancer invasion and migration.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4711-4715
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• 2013

Aim: The aim of this study was to evaluate acute adverse events and efficacy of three-dimensional intensitymodulated radiotherapy (IMRT) combined with endocrine therapy for intermediate and advanced prostate cancer. Methods: Sixty-seven patients were treated with three-dimensional IMRT combined with maximum androgen blockade. The correlation between radiation-induced rectal injury and clinical factors was further analyzed. Results: After treatment, 21 patients had complete remission (CR), 37 had partial remission (PR), and nine had stable disease (SD), with an overall response rate of 86.5%. The follow-up period ranged from 12.5 to 99.6 months. Thirty-nine patients had a follow-up time of ${\geq}$ five years. In this group, three-year and five-year overall survival rates were 89% and 89.5%, respectively; three-year and five-year progression-free survival rates were 72% and 63%. In univariate analyses, gross tumor volume was found to be prognostic for survival ($X^2$ = 5.70, P = 0.037). Rates of leucopenia and anemia were 91.1% and 89.5%, respectively. Two patients developed acute liver injury, and a majority of patients developed acute radiation proctitis and cystitis, mainly grade 1/2. Tumor volume before treatment was the only prognostic factor influencing the severity of acute radiation proctitis (P < 0.05). Conclusions: IMRT combined with endocrine therapy demonstrated promising efficacy and was well tolerated in patients with intermediate and advanced prostate cancer.

• International Journal of Aeronautical and Space Sciences
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• 제8권1호
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• pp.10-20
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• 2007

For spacecraft attitude control, reaction wheel (RW) steering laws with more than three wheels for three-axis attitude control can be derived by using a control allocation (CA) approach.1-2 The CA technique deals with a problem of distributing a given control demand to available sets of actuators.3-4 There are many references for CA with applications to aerospace systems. For spacecraft, the control torque command for three body-fixed reference frames can be constructed by a combination of multiple wheels, usually four-wheel pyramid sets. Multi-wheel configurations can be exploited to satisfy a body-axis control torque requirement while satisfying objectives such as minimum control energy.1-2 In general, the reaction wheel steering laws determine required torque command for each wheel in the form of matrix pseudo-inverse. In general, the attitude control command is generated in the form of a feedback control. The spacecraft body angular rate measured by gyros is used to estimate angular displacement also.⁵ Combination of the body angular rate and attitude parameters such as quaternion and MRPs(Modified Rodrigues Parameters) is typically used in synthesizing the control command which should be produced by RWs.¹ The attitude sensor signals are usually corrupted by noise; gyros tend to contain errors such as drift and random noise. The attitude determination system can estimate such errors, and provide best true signals for feedback control.⁶ Even if the attitude determination system, for instance, sophisticated algorithm such as the EKF(Extended Kalman Filter) algorithm⁶, can eliminate the errors efficiently, it is quite probable that the control command still contains noise sources. The noise and/or other high frequency components in the control command would cause the wheel speed to change in an undesirable manner. The closed-loop system, governed by the feedback control law, is also directly affected by the noise due to imperfect sensor characteristics. The noise components in the sensor signal should be mitigated so that the control command is isolated from the noise effect. This can be done by adding a filter to the sensor output or preventing rapid change in the control command. Dynamic control allocation(DCA), recently studied by Härkegård, is to distribute the control command in the sense of dynamics⁴: the allocation is made over a certain time interval, not a fixed time instant. The dynamic behavior of the control command is taken into account in the course of distributing the control command. Not only the control command requirement, but also variation of the control command over a sampling interval is included in the performance criterion to be optimized. The result is a control command in the form of a finite difference equation over the given time interval.⁴ It results in a filter dynamics by taking the previous control command into account for the synthesis of current control command. Stability of the proposed dynamic control allocation (CA) approach was proved to ensure the control command is bounded at the steady-state. In this study, we extended the results presented in Ref. 4 by adding a two-step dynamic CA term in deriving the control allocation law. Also, the strict equality constraint, between the virtual and actual control inputs, is relaxed in order to construct control command with a smooth profile. The proposed DCA technique is applied to a spacecraft attitude control problem. The sensor noise and/or irregular signals, which are existent in most of spacecraft attitude sensors, can be handled effectively by the proposed approach.