• BMB Reports
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• 제54권2호
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• pp.136-141
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• 2021

Thyroid eye disease (TED) is a complex autoimmune disease with a spectrum of signs. we previously reported that trisialoganglioside (GT)1b is significantly overexpressed in the orbital tissue of TED patients, and that exogenous GT1b strongly induced HA synthesis in orbital fibroblasts. However, the signaling pathway in GT1b-induced hyaluronic acid synthase (HAS) expression in orbital fibroblasts from TED patients have rarely been investigated. Here, we demonstrated that GT1b induced phosphorylation of Akt/mTOR in a dose-dependent manner in orbital fibroblasts from TED patients. Both co-treatment with a specific inhibitor for PI3K and siRNA knockdown of TLR2 attenuated GT1b-induced Akt phosphorylation. GT1b significantly induced HAS2 expression at both the transcriptional and translational level, which was suppressed by specific inhibitors of PI3K or Akt/mTOR, and by siRNA knockdown of TLR2. In conclusion, GT1b induced HAS2 in orbital fibroblasts from TED patients via activation of the PI3K-related signaling pathway, dependent on TLR2.

• 디지털융복합연구
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• 제20권5호
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• pp.761-776
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• 2022

바이오·의료 산업의 전략적 육성을 위해 첨단기술 중심의 혁신클러스터 조성이 추진되고 있다. 이에 따라 해외 주요 클러스터에 관한 사례연구 등을 바탕으로 국내 클러스터에의 시사점을 다룬 연구들이 이뤄지고 있으나, 개별 사례에 국한된다는 한계가 있었다. 본 논문에서는 바이오·의료 클러스터의 조성과 활성화를 위해 고려되어야 할 요인들을 종합적으로 정리하고자, 혁신클러스터 및 바이오·의료 산업에 관한 문헌들을 대상으로 내용분석(content analysis)을 수행하였다. 식별된 요인들은 크게 두 가지 그룹으로 나뉘었는데 클러스터의 성장단계에 따른 영향요인과 또 바이오 클러스터에서 구별되어 나타나는 조성조건으로 구분하였다. 이어서 내용분석을 통해 도출한 사항들을, 홍릉 강소연구개발특구의 사례에 적용하였다. 홍릉 강소연구개발특구의 성공적 조성을 위해서는 정주여건 개선, 창업문화 활성화, 제도 마련과 동시에 바이오·의료 산업에 특화된 접근인 중개연구 활성화와 투자 유치 그리고 지역 클러스터와의 협력과 연계가 요구된다.

• Molecules and Cells
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• 제40권9호
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• pp.667-676
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• 2017

Abnormal differentiation of muscle is closely associated with aging (sarcopenia) and diseases such as cancer and type II diabetes. Thus, understanding the mechanisms that regulate muscle differentiation will be useful in the treatment and prevention of these conditions. Protein lysine acetylation and methylation are major post-translational modification mechanisms that regulate key cellular processes. In this study, to elucidate the relationship between myogenic differentiation and protein lysine acetylation/methylation, we performed a PCR array of enzymes related to protein lysine acetylation/methylation during C2C12 myoblast differentiation. Our results indicated that the expression pattern of HDAC11 was substantially increased during myoblast differentiation. Furthermore, ectopic expression of HDAC11 completely inhibited myoblast differentiation, concomitant with reduced expression of key myogenic transcription factors. However, the catalytically inactive mutant of HDAC11 (H142/143A) did not impede myoblast differentiation. In addition, wild-type HDAC11, but not the inactive HDAC11 mutant, suppressed MyoD-induced promoter activities of MEF2C and MYOG (Myogenin), and reduced histone acetylation near the E-boxes, the MyoD binding site, of the MEF2C and MYOG promoters. Collectively, our results indicate that HDAC11 would suppress myoblast differentiation via regulation of MyoD-dependent transcription. These findings suggest that HDAC11 is a novel critical target for controlling myoblast differentiation.

• Journal of Gastric Cancer
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• 제23권4호
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• pp.609-621
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• 2023

Purpose: Determination of optimal treatment strategies for HER2-positive advanced gastric cancer (AGC) in randomized trials is necessary despite difficulties in direct comparison between trastuzumab deruxtecan (T-DXd) and nivolumab as third or later-line treatments. Materials and Methods: This single-institution, retrospective study aimed to describe the real-world efficacy and safety of T-DXd and nivolumab as ≥ third line treatments for HER2-positive AGC between March 2016 and May 2022. Overall, 58 patients (median age, 64 years; 69% male) were eligible for the study (T-DXd group, n=20; nivolumab group, n=38). Results: Most patients exhibited a HER2 3+ status (72%) and presented metastatic disease at diagnosis (66%). The response rates of 41 patients with measurable lesions in the T-DXd and nivolumab groups were 50% and 15%, respectively. The T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95% confidence interval [CI], 3.3, 7.0) and 2.3 months (95% CI, 1.5, 3.5), median overall survival (OS) of 10.8 months (95% CI, 6.9, 23.8) and 11.7 months (95% CI, 7.6, 17.1), and grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% patients received subsequent treatment. Among 23 patients who received both regimens, the T-DXd-nivolumab and nivolumab-T-DXd groups had a median OS of 14.0 months (95% CI, 5.0, not reached) and 19.3 months (95% CI, 9.5, 25.1), respectively. Conclusions: T-DXd and nivolumab showed distinct efficacy and toxicity profiles as ≥ third line treatments for HER2-positive AGC. Considering the distinct features of each regimen, they may help clinicians personalize optimal treatment approaches for these patients.

• 대한조선학회논문집
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• 제49권2호
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• pp.203-211
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• 2012

The main object of this experiment is to estimate the hydrodynamic forces acting on a submerged streamlined body placed in a one-end-opened cylindrical tube moving with certain translational velocity. The best experimental design for this object is mimicking real situation, however sizes of model body and cylinder tube are just the same as those of real, for avoiding scale effects, mimicking real situation is not realizable. Hence, in this experiment, target body and cylindrical tube were designed to be towed with varying body position relative to cylindrical tube. For measuring hydrodynamic forces and flow velocity in the cylindrical tube, six one-component load cells and several one-hole Pitot tubes were used. Several conditions were checked with various end-plates those had different opening areas. Experiment results show that forces and flow velocity had different tendency with those expected, and the presence of a end-plate slows down the flow velocity in the cylindrical tube and affects pressure field in the tube to push the model submerged body forward of the tube. This tendency grows with decreasing opened area.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6973-6979
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• 2015

Background: Ovarian cancer is the third most common cause of cancer in Indian women. Despite an initial 70-80% response rate, most patients relapse within 1-2 years and develop chemoresistance. Hence, identification or repositioning of drugs to resensitise ovarian cancer cells to existing chemotherapy is needed. Traditionally immortalized cell lines have been used in research, but these may contain genetic aberrations and chromosomal abnormalities serving as poor indicators of normal cell phenotype and progression of early-stage disease. The use of primary cells, maintained for only short periods of time in vitro, may serve as the best representative for studying in vivo conditions of the tissues from which they are derived. In this study we have attempted to evaluate the effect of metformin (an antidiabetic drug) in primary ovarian cancer cells because of its promising effect in other solid tumours. Materials and Methods: Primary cultures of epithelial ovarian cancer cells established from ascitic fluid of untreated ovarian cancer patients were used. The cells were treated with metformin at doses standardized by MTT assay and its ability to induce apoptosis was studied. The cells were analysed for apoptosis and apoptosis related proteins by flow cytometry and western blotting respectively. Results: Metformin induced apoptosis in ovarian cancer cells, provoking cell cycle arrest in the G0/G1 and S phase. It induced apoptosis in ovarian cancer cells by, down-regulating Bcl-2 and up-regulating Bax expression. Conclusions: Metformin was able to induce apoptosis in primary ovarian cancer cells by modulating the expression of Bcl-2 family proteins. These data are relevant to ongoing translational research efforts exploring the chemotherapeutic potential of metformin.

• 한국미생물·생명공학회지
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• 제46권3호
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• pp.244-252
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• 2018

Protein disulfide isomerase A3 (PDIA3) is a major member of the protein disulfide isomerase (PDI) family. PDI proteins commonly reside in the endoplasmic reticulum and mediate important thiol-disulfide interchanges during post-translational protein folding. Unlike other PDI family members, PDIA3 is ubiquitous in various organ systems. However, its physiological activity varies in other tissues. PDIA3 has been associated with cancer, airway inflammation, neurodegenerative diseases, and metabolic diseases. However, the mechanisms of the association of PDIA3 with these pathological conditions remain unclear. Recombinant PDIA3 (rPDIA3) is needed to clarify the interactions between PDIA3 and certain physiological phenomena. In the present study, we aimed to produce highly purified rPDIA3 for use in pathological experiments. We expressed rPDIA3 with a histidine-enriched elongated peptide tag in Escherichia coli and obtained rPDIA3 at 97.8% purity using consecutive His-tag and reverse-phase chromatography. Elongated peptide tags screened from artificially designated library had dual functions for protein expression and simple purification.

• Journal of Microbiology and Biotechnology
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• 제18권2호
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• pp.219-227
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• 2008

The free-living photoheterotrophic Gram-negative bacterium Rhodobacter sphaeroides possesses a quorum-sensing (QS) regulatory system mediated by CerR-CerI, a member of the LuxR-LuxI family. To identify the genes affected by the regulatory system, random lacZ fusions were generated in the genome of R. sphaeroides strain 2.4.1 using a promoter-trapping vector, pSG2. About 20,000 clones were screened and 23 showed a significantly different level of ${\beta}$-gal activities upon the addition of synthetic 7,8-cis-N-tetradecenoyl-homoserine lactone (RAI). Among these 23 clones, the clone showing the highest level of induction was selected for further study, where about a ten-fold increase of ${\beta}$-gal activity was exhibited in the presence of RAI and induction was shown to be required for cerR. In this clone, the lacZ reporter was inserted in a putative gene that exhibited a low homology with catD. A genetic analysis showed that the expression of the catD homolog was initiated from a promoter of another gene present upstream of the catD. This upstream gene showed a strong homology with luxR and hence was named qsrR (quorum-sensing regulation regulator). A comparison of the total protein expression profiles for the wild-type cells and qsrR-null mutant cells using two-dimensional gel electrophoresis and a MALDI-TOF analysis allowed the identification of sets of genes modulated by the luxR homolog.

• 대한기계학회논문집A
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• 제26권12호
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• pp.2636-2646
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• 2002

This research presents an analytical model to investigate vibration due to ball bearing waviness in a rotating system supported by two or more ball bearings, taking account of the centrifugal force and gyroscopic moment of the ball. The waviness of rolling elements is modeled by the sinusoidal function, and it is incorporated into the position vectors of the race curvature center. The Hertzian con tact theory is applied to calculate the elastic deflection and nonlinear contact force while the rotor has translational and angular motions. Both the centrifugal force and gyroscopic moment of the ball and the waviness of the rolling elements are included in the kinematic constraints and force equilibrium equations of a ball to derive the nonlinear governing equations of the rotor, which are solved by using the Runge-Kutta-Fehlberg algorithm to determine the new position of the rotor. The proposed model is validated by the comparison of the results of the prior researchers. This research shows that the centrifugal force and gyroscopic moment of the ball plays the important role in determining the bearing frequencies, i.e. the principal frequencies, their harmonics and the sideband frequencies resulting from the waviness of the rolling elements of ball bearing. It also shows that the bearing vibration frequencies are generated by the waviness interaction not only between the rolling elements of one ball bearing but also between those of two or more ball bearings constrained by the rotor.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7701-7705
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• 2015

Background: Thyroid hormones (TH) are regulated by the hypothalamic-pituitary axis, which plays an important role in cell growth, differentiation, development and other aspects of metabolism. It is believed that an active hypothalamic-pituitary axis increases the susceptibility of thyroid dysfunction during systemic chemotherapy. In order to investigate the relation between thyroid function and chemotherapy the present study was designed to investigate TH in breast cancer patients receiving at least three cycles of chemotherapy. The levels of TH were measured at the baseline and before each cycle of chemotherapy. Materials and Methods: Blood samples for estimation of TH levels were collected from 80 (pre-menopausal-40; post-menopausal-40) breast cancer patients just before they were undergoing - $1^{st}$, $2^{nd}$, $3^{rd}$ and $4^{th}$ cycle of chemotherapy. The serum was separated and $T_3$, $T_4$ and TSH levels were determined by chemiluminescence method. Results: $T_3$ and $T_4$ were found significantly decreased and TSH was found significantly increased after $1^{st}$ (p<0.001), $2^{nd}$ (p<0.0001) and $3^{rd}$ cycle of chemotherapy (p<0.0001). The variation of $T_3$ levels (decreased) and TSH levels (increased) was found more in post-menopausal (p<0.0001) women then in pre-menopausal women after $3^{rd}$ cycle of chemotherapy as compared to baseline (p<0.001). Conclusions: TH were remarkably altered after each cycle of chemotherapy leading to decline in thyroid function of breast cancer patients. Further, the results also indicated that post-menopausal women were more prone towards decline in thyroid function then pre-menopausal women. The present study proposes the monitoring of TH after each cycle of chemotherapy in breast cancer patients.