Drug evaluation based on phosphomimetic PDHA1 reveals the complexity of activity-related cell death in A549 non-small cell lung cancer cells

( Ling Jin ),( Minkyoung Cho ),( Bo-sung Kim ),( Jung Ho Han ),( Sungmi Park ),( In-kyu Lee ),( Dongryeol Ryu ),( Jae Ho Kim ),( Sung-jin Bae ),( Ki-tae Ha ) 생화학분자생물학회 2021 BMB Reports Vol.54 No.11

Cancer cells predominantly generate energy via glycolysis, even in the presence of oxygen, to support abnormal cell proliferation. Suppression of PDHA1 by PDK1 prevents the conversion of cytoplasmic pyruvate into Acetyl-CoA. Several PDK inhibitors have been identified, but their clinical applications have not been successful for unclear reasons. In this study, endogenous PDHA1 in A549 cells was silenced by the CRISPR/Cas9 system, and PDHA1^WT and PDHA1^3SD were transduced. Since PDHA1^3SD cannot be phosphorylated by PDKs, it was used to evaluate the specific activity of PDK inhibitors. This study highlights that PDHA1^WT and PDHA1^3SD A549 cells can be used as a cell-based PDK inhibitor-distinction system to examine the relationship between PDH activity and cell death by established PDK inhibitors. Leelamine, huzhangoside A and otobaphenol induced PDH activity-dependent apoptosis, whereas AZD7545, VER-246608 and DCA effectively enhanced PDHA1 activity but little toxic to cancer cells. Furthermore, the activity of phosphomimetic PDHA1 revealed the complexity of its regulation, which requires further in-depth investigation. [BMB Reports 2021; 54(11): 563-568]

Results of Fertility preservation program: A single center cohort study

( Jung Ah Roh ),( Bo Hyon Yun ),( Jae Hoon Lee ),( Minkyoung Kim ),( Seok Kyo Seo ),( Sihyun Cho ),( Young Sik Choi ),( Byung Seok Lee ),( Jung Ah Roh ),( Bo Hyon Yun ),( Jae Hoon Lee ),( Minkyoung Ki 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

목적: The aim of the study was to review the experience of fertility preservation (FP) program in a single center and to evaluate efficacy of FP referral program. 방법: From January 2013 to January 2016, the patients who have concern for their fertility that were referred to FP program were included. The age of patients at the time of discussing fertility preservation was under 40 years old. Total 103 patients who have undergone fertility preservation program in Severance hospital, Yonsei University College of Medicine were included. Statistical analyses were performed using chi-square test, Mann Whitney U test, and Kruscal-Wallis test according to the variables. 결과: Total 63 patients have undergone either embryo or oocyte cryopreservation, performing 82 controlled ovarian hyperstimulation cycles. Breast cancer patients composed the most: 15 patients (53.6%), 16 cycles of embryo; 22 patients (62.86%), 22 cycles of oocyte cryopreservation. Otherwise, patients diagnosed sarcoma, gastrointestinal, gynecological, and hematologic malignancy have been done the cryopreservation. Total 92 patients have received gonadotropin releasing hormone agonist for FP purpose. As similar as embryo/oocyte cryopreservation, patients with breast cancer composed the most: 46 patients (50%). The first 6 months follow up with serum anti-Mullerian hormone showed 0.23ng/dL (<0.08-13.41) in patients with breast cancer, 0.61ng/dL (<0.08-2.98) in patients with hematologic malignancy. The FP referral program between breast cancer clinic and infertility clinic was set since January 2015, and comparing the referral rate and FP rate between and after the FP program, significant increase was shown. However, referral and FP rate were similar in other cancers during the same time. 결론: The effective FP program between oncology department and infertility clinic seems to increase the rate of referral and participating FP program. Those who are expected to receive treatment that might affect fertility, should discuss about the FP options.

Epigenetic modulation of the muscarinic type 3 receptor in salivary epithelial cells.

Shin, Yong-Hwan,Jin, Meihong,Hwang, Sung-Min,Choi, Seul-Ki,Namkoong, Eun,Kim, Minkyoung,Park, Moon-Yong,Choi, Se-Young,Lee, Jong-Ho,Park, Kyungpyo United States and Canadian Academy of Pathology [e 2015 Laboratory investigation Vol.95 No.2

<P>Muscarinic receptors, particularly the type 3 subtype (M3R), have an important role in exocrine secretion. M3R normally function in HSG cells originated from human submandibular gland ducts, but not in A253 and SGT cells, derived from human submandibular carcinoma and salivary gland adenocarcinoma. However, the underlying mechanism of this suppression has remained elusive. In this study, we examined whether M3R function is suppressed by epigenetic modulation of the receptor. To this end, we investigated the mRNA transcript and protein levels of the M3R using reverse transcriptase-PCR, western blot, and confocal microscopy analyses. Global DNA methylation assays, methylation-specific PCR, and bisulfite sequencing were also performed to understand the epigenetic status of the M3R CpG island. We found that A253 cells expressed all subtypes of muscarinic receptors, except M3R, on the mRNA level. However, treatment of cells with 5-aza-2'-deoxycytidine (5-Aza-CdR), a DNA-demethylating agent, increased the expression levels of both M3R mRNA transcript and protein in proportion to the incubation period. 5-Aza-CdR completely restored the carbachol-induced calcium response, which was not observed in untreated A253 cells. In untreated A253 cells, all CG pairs from the 1st to 14th were methylated and 5-Aza-CdR treatment demethylated one of the methylated CG pairs. We also examined the methylation pattern of M3R CpG island in human cancer tissue. Interestingly, the result was very similar to those of A253 cells. All CG pairs in M3R CpG island were also methylated. Another salivary gland tumor cell line, SGT, also showed the similar methylation pattern, heavy methylation in M3R CpG island. It is concluded that CpG island in M3R is hypermethylated in cancer cell lines and human cancer. Our results further suggest that 5-Aza-CdR could potentially be used to restore the function of M3R, suppressed in some cancer cell types.</P>

호혜적 개발협력을 위한 주요 국가의 STI 시스템 분석 및 협력방향 - 브라질, 인도를 중심으로 -

김왕동(Wangdong Kim),임덕순(Deok Soon Yim),선인경(Inkyoung Sun),김은주(Eun Joo Kim),이다은(Daeun Lee),유제현(Jehyun Yu),이정원(Jung-won Lee),김기국(Ki-Kook Kim),최용인(Yongin Choi),김원호(Wonho Kim),조충제(Chungje Jo),박민경(Minkyoung P 과학기술정책연구원 2021 정책연구 Vol.- No.-

Reciprocal development cooperation refers to “all activities in the public and private sectors that benefit the donor country’s national interest as well as poverty eradication and economic and social development in the recipient country”. The Korean governments development cooperation paradigm is expected to gradually shift from a humanitarian level to a reciprocal level. However, in the case of science and technology innovation, it is difficult to acquire information about countries that are subject to reciprocal development cooperation. Therefore, in this study, the conceptual framework for reciprocal development cooperation was established and STI systems of major countries were analyzed to provide basic STI data and to suggest directions for reciprocal development cooperation. In this study, two countries, Brazil and India, were selected for analysis by applying three criteria: “differentiation from existing research,” “relevance to national interests and national tasks,” and “possibility of securing data”. In this study, the STI system components of Brazil and India were classified and analyzed into macro-environment, STI governance, STI investment and achievements, STI human resources, STI innovative actors, and STI support organizations. The reciprocal development cooperation agenda was described focusing on three dimensions: “what”, “how” and “who”. First, in the perspective of “what”, climate change, digital transformation, infectious diseases, and other issues were derived as cooperation contents. Second, policy advice and joint research, human exchange, and so on, were suggested as cooperation methods. Third, universities, GRIs, and companies were suggested as cooperation partners. Brazils STI system is characterized by a weak national R&D budget, excellent research manpower and strong basic research, lack of connection and creation of innovation demand between universities and companies, weak industrial competitiveness, lack of science and technology policy and strategy, policy implementation, and coordination of inefficiency and slow-step administration. The characteristics of the Indian STI system include inefficient governance and lack of interconnection led by the government, insufficient investment in STI between the government and the private sector, abundant STI manpower and global talent, the pursuit of R&D activities centered on universities and public research institutes rather than the private sector, bureaucratic and bureaucratic An inefficient STI support organization was identified. In-depth interviews and consultations were conducted with experts from each country to derive the Korea-Brazil development cooperation agenda and the Korea-India development cooperation agenda. The interview and advisory groups were largely divided into policymakers(public officials) for each country, researchers(researchers and professors), and local experts(embassies and dispatchers). The detailed agenda contents are described in Chapters 6 and 7. This study is expected to contribute to the theoretical construction of the field of development cooperation, and to the derivation of the governments Korea-Brazil and Korea-India STI cooperation agenda. The study also can contribute to the demand for STI system information of Brazil and India. However, this study has limitations in responding to more demand by the government by selecting Brazil and India as two countries for reciprocal development cooperation. Therefore many more countries besides Brazil and India should be explored in the future. In addition, in order to improve the reliability and validity of the STI cooperation agenda between Korea-Brazil and Korea-India, interviews and consultations with more experts are required.