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CDK7 as a potential therapeutic target for ovarian cancer; preclinical study
( Jihye Kim ),( Young Sun Lim ),( Young-jae Cho ),( Soo Young Jeong ),( Myeong Sun Kim ),( E Sun Paik ),( Chel Hun Choi ),( Tae-joong Kim ),( Byoung-gie Kim ),( Duk-soo Bae ),( Jeong-won Lee ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-
Objective: Cyclin dependent kinases (CDKs) are involved in temporal regulation of the cell cycle and transcription and play central roles in cancer development and metastasis. CDK7 activates cell cycle CDKs and is a member of the general transcription factor TFIIH. In this study, we evaluate the therapeutic effects of CDK7 inhibition in ovarian cancer using in vitro and in vivo models. Methods: We analyzed the clinical significance of CDK7 expression using TCGA data. Using CDK7 siRNA or covalent CDK7 inhibitor (THZ1), we performed the cell proliferation, apoptosis and the effects of cell cycle analysis in ovarian cancer cell lines including A2780, HeyA8, A2780-CP20 and RMG1. Based on in vitro results, we also performed in vivo experiments including cell line xenograft (A2780) and patient-derived xenografts (PDXs). Results: Higher CDK7 expression is significantly associated with poor progression-free survival of ovarian cancer patients in the analysis of TCGA data. CDK7 suppression with its siRNA or THZ1 significantly decreased cell proliferation and increased apoptosis with cell line experiments. Moreover, combination treatment with CDK7 inhibition and cisplatin decreased cell proliferation in drug-resistant A2780-CP20 cells. In the flow cytometric analysis to check the influence in cell cycle of CDK7 inhibition, we found that THZ1 triggered G0/G1 cell cycle arrest in a dose-dependent manner. In in vivo therapeutic experiment with cell line xenograft, CDK7 suppression with its siRNA or THZ1 could significantly decrease the tumor weight in A2780 and HeyA8 models. Moreover, we also found similar effect of this treatment in a PDX model with clear cell carcinoma. Conclusion: These results showed that CDK7 suppression with its siRNA or THZ1 could significantly suppress ovarian cancer growth in in vitro and in vivo by triggering G0/G1 cell cycle arrest. Therefore, CDK7 might be a novel promising therapeutic target for ovarian cancer and will be explored in the near future for therapy of ovarian cancer.
Marinopyrones A-D, α-pyrones from marine-derived actionmycetes of the family Nocardiopsaceae
( Jihye Lee ),( Chulkyeong Han ),( Tae Gu Lee ),( Jungwook Chin ),( Hyukjae Choi ),( Wonjae Lee ),( Man Jeong Paik ),( Dong Hwan Won ),( Gyusang Jeong ),( Jaeyoung Ko ),( Yeo Joon Yoon ),( Sang Jip Na 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-
Two actinomycetes, a member of the rare halophilic genus Streptomonospora and a Nocardiopsis sp. (Nocardiopsaceae), strains CNQ-082 and CNQ-675, respectively. were isolated from marine sediments collected off shore near La Jolla. California. HPLC-UV guided fractionations of the extracts of these strains yielded marinopyrones A-D (1-4), the structures of which were elucidated by interpretation of 10 and 20 NMR and HRMS spectroscopic data. Oxidative ozonation, followed by conversion of the acid product to an α-naphthyl amide, provided the absolute configuration at the chiral center on the side-chain. Marinopyrones A-D were examined for the inhibitory activity on nitric oxide production in LPS-activated mouse macrophage cells (RAW 264.7); marinopyrone D (4) was inhibitory with an IC<sub>50</sub> value of 13 I``M. To our knowledge, marinopyrones A-C are only the second reported natural products from the rare halophi-lic genus Streptomonospora.
( Jihye Kim ),( Soo Young Jeong ),( Myeong Seon Kim ),( E Sun Paik ),( Chel Hun Choi ),( Tae Joong Kim ),( Byoung-gie Kim ),( Duk-soo Bae ),( Jeong-won Lee ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-
Objective: Knotless, absorbable barbed suture devices have been widely used in gynecologic surgery, especially, suturing myometrium in laparoscopic myomectomy. MonofixTM has a triangular stopper which acts as anchor at the end of device. The objective of this study was to compare the biomechanical strength and histologic features of MonofixTM with other barbed suture devices in intradermal skin wound closure and fascial closure in porcine model. Methods: Sixteen female domestic pigs were randomly assigned to one of 4 groups designated by postoperative day of assessment. Twelve skin incisions were made along the dorsum in the thoracolumbar region of each pig with an equal number (n=4) randomly assigned to closure with 3-0 MonofixTM and controls. Pigs were euthanatized on postoperative days 3, 7, 14, and 28, respectively. The skin incision specimens were harvested for biomechanical testing and histologic evaluation. Five female domestic pigs were included in fascial closure group. Each had two paramedian incisions, one fascial incision was closed with 2-0 MonofixTM, and the other was closed with control. At 6 weeks, the fascia excised and the suture line were tested with histologic evaluation. Results: In the ex-vivo biomechanical analysis of intradermal closure, MonofixTM shows similar tissue tensile strength compared with other commercially used barbed suture devices, regardless of day. All three test articles resulted in mild tissue reaction scores in histology, however, the average tissue reaction score was no difference between MonofixTM and controls. There were no significant complications in all three suture devices. In fascial closure group, there were no wound infections and incisional hernias. Also, the average tissue reaction score of fasical closure group was no difference between MonofixTM and control. Conclusion: This preclinical study suggests that the use of barbed suture devices with stopper (MonofixTM) can be a safe and efficacious alternative compared with other barbed suture devices. Acknowledgements: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), fun
기능기반의 중재가 지적장애 학생의 과제 수행 행동, 과제 완성도, 과제 정확도에 미치는 효과
정지혜(JIhye Jeong),정선화( Sunhwa Jung) 한국행동분석학회 2023 행동분석․지원연구 Vol.10 No.3
이 연구는 기능기반의 중재가 지적장애 초등학생의 과제 수행 행동, 과제 완성도 및 과제 정확도에 미치는 효과에 대해 평가하였다. 수업 시간에 과제 이탈 행동을 보이는 지적장애 학생 두 명이 연구에 참여하였다. 연구 참여 학생들의 행동에 대한 기능평가를 실시하였고, 평가 결과에 기반하여 중재를 계획하고, 제공하였다. 중재에 대한 효과는 상황 간 중다기초선 설계를 사용하여 평가하였다. 실험은 기초선, 중재, 유지 단계의 순으로 진행하였으며, 각 실험 단계에서 일반화 효과를 평가하였다. 연구 결과 중재가 제공되자 연구 참여 학생의 과제 수행 행동, 과제 완성도 및 과제 정확도가 향상되었고, 중재가 제거된 후에도 중재 효과가 유지되었다. 연구 참여 학생의 보호자와 담임교사는 중재 목표의 중요성, 절차의 적절성, 효과에 대한 사회적 타당도 평가에서 매우 긍정적인 반응을 보였다. The purpose of this study was to investigate the effects of function-based intervention on active task engagement, task completion, and task accuracy. Two elementary school students with mild intellectual disabilities who exhibit off-task behavior in class participated in the study. Functional behavioral assessments were conducted, the function-based intervention was implemented to improve the participants’ behaviors, and the effects of the intervention were evaluated using a multiple baseline across settings design. The experiment was conducted as baseline, intervention, maintenance, and generalization during each experimental condition. The results indicated that the active task engagement, task completion, and task accuracy of both participants were increased after providing the intervention and maintained after removing the intervention. The parents of the participants and classroom teachers highly evaluated the social validity in terms of the intervention goals, the appropriateness, and the outcomes of the intervention.