• Title/Summary/Keyword: Biomedicine

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'Drawing' a Molecular Portrait of CIN and Cervical Cancer: a Review of Genome-Wide Molecular Profiling Data

  • Kurmyshkina, Olga V;Kovchur, Pavel I;Volkova, Tatyana O
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4477-4487
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    • 2015
  • In this review we summarize the results of studies employing high-throughput methods of profiling of HPV-associated cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancers at key intracellular regulatory levels to demonstrate the unique identity of the landscape of molecular changes underlying this oncopathology, and to show how these changes are related to the 'natural history' of cervical cancer progression and the formation of clinically significant properties of tumors. A step-wise character of cervical cancer progression is a morphologically well-described fact and, as evidenced by genome-wide screenings, it is indeed the consistent change of the molecular profiles of HPV-infected epithelial cells through which they progressively acquire the phenotypic hallmarks of cancerous cells. In this sense, CIN/cervical cancer is a unique model for studying the driving forces and mechanisms of carcinogenesis. Recent research has allowed definition of the whole-genome spectrum of both random and regular molecular alterations, as well as changes either common to processes of carcinogenesis or specific for cervical cancer. Despite the existence of questions that are still to be investigated, these findings are of great value for the future development of approaches for the diagnostics and treatment of cervical neoplasms.

Frontal Alpha Asymmetry, Heart Rate Variability, and Positive Resources in Bereaved Family Members with Suicidal Ideation after the Sewol Ferry Disaster

  • Jang, Kuk-In;Lee, Sangmin;Lee, Seung-Hwan;Chae, Jeong-Ho
    • Psychiatry investigation
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    • v.15 no.12
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    • pp.1168-1173
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    • 2018
  • Objective After the Sewol ferry disaster, bereavement with suicidal ideation was a critical mental health problem that was accompanied by various neuropsychological symptoms. This study examined the frontal alpha asymmetry (FAA), heart rate variability (HRV), and several psychological symptoms in bereaved family members (BFM) after the Sewol ferry disaster. Methods Eighty-three BFM after the Sewol ferry disaster were recruited. We assessed FAA, HRV, and psychological symptoms, including depression, post-traumatic stress, post-traumatic growth factor, anxiety, grief, and positive resources, between BFM with the presence and absence of current suicidal ideation. Results Compared to BFM without suicidal ideation, BFM with suicidal ideation showed a higher FAA with right dominance. Significant differences in psychological symptoms were observed between the groups. In BFM with suicidal ideation, the low: high frequency (LF:HF) ratio correlated with social resources and support. Conclusion The FAA and LF:HF ratio may be biomarkers that represent the pathological conditions of BFM with suicidal ideation. If researched further, they may shed light on the interaction between bereavement with suicidal ideation and social resources for therapeutic intervention.

The Chronic and Acute Toxicity of Traditional Medicines Containing Terminalia chebula

  • ARONGQIQIGE ARONGQIQIGE;Gerelmaa Enebish;Wang Song;Wei Cheng Xi;Anuujin Gantumur;Oyunbaatar Altanbayar;Hirofumi Shimomura;Battogtokh Chimeddorj;Batnairamdal Chuluun;Avarzed Amgalanbaatar
    • Journal of Pharmacopuncture
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    • v.26 no.1
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    • pp.18-26
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    • 2023
  • Objectives: Terminalia chebula, the main ingredient of Altan Arur 5, has been used for many years in traditional medicine. This medicine is more effective than other drugs and is used to treat chronic gastritis and gastrointestinal disorders such as peptic ulcers and esophageal reflux. Other ingredients of Altan Arur 5 are Punica granatum (pomegranate), tulip seeds, black balm, and excreta of Trogopterus xanthipes. The main ingredients of T. chebula are antibacterial and analgesic in traditional medicine. Despite having been used for many years and although many studies have been conducted on the beneficial effects of this medicine and its ingredients, the toxicity of Altan Arur 5 has not yet been elucidated. Therefore, we aimed to study the toxicity of Altan Arur 5 to ensure that it is safe to use. Methods: Acute and chronic toxicity of Altan Arur 5 were assessed in 10 Kunming mice and 8 Sprague-Dawley rats, respectively, in different doses. In the acute toxicity study, Altan Arur 5 was orally administered to Kunming mice in doses of 12 g/kg, 24 g/kg, and 48 g/kg for 14 days. In the chronic toxicity study, it was orally administered to Sprague-Dawley rats in doses of 1.25 g/kg, 2.5 g/kg, and 5 g/kg for 12 weeks. Results: No significant differences were observed in the relative organ weights for mice treated with Altan Arur 5 compared with those in the control group. Furthermore, no macro- or microstructural changes were noted in the organs of any group. Conclusion: Our toxicity testing revealed that the traditional medicine Altan Arur 5 has no toxic effects in vivo.

3-Deoxysappanchalcone Inhibits Cell Growth of Gefitinib-Resistant Lung Cancer Cells by Simultaneous Targeting of EGFR and MET Kinases

  • Jin-Young Lee;Seung-On Lee;Ah-Won Kwak;Seon-Bin Chae;Seung-Sik Cho;Goo Yoon;Ki-Taek Kim;Yung Hyun Choi;Mee-Hyun Lee;Sang Hoon Joo;Jin Woo Park;Jung-Hyun Shim
    • Biomolecules & Therapeutics
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    • v.31 no.4
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    • pp.446-455
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    • 2023
  • The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anti-cancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.

Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin

  • Seung-On Lee;Sang Hoon Joo;Jin-Young Lee;Ah-Won Kwak;Ki-Taek Kim;Seung-Sik Cho;Goo Yoon;Yung Hyun Choi;Jin Woo Park;Jung-Hyun Shim
    • Biomolecules & Therapeutics
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    • v.32 no.1
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    • pp.104-114
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    • 2024
  • Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

Comparison of binary data imputation methods in clinical trials (임상시험에서 이분형 결측치 처리방법의 비교연구)

  • An, Koosung;Kim, Dongjae
    • The Korean Journal of Applied Statistics
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    • v.29 no.3
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    • pp.539-547
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    • 2016
  • We discussed how to handle missing binary data clinical trials. Patterns of occurring missing data are discussed and introduce missing binary data imputation methods that include the modified method. A simulation is performed by modifying actual data for each method. The condition of this simulation is controlled by a response rate and a missing value rate. We list the simulation results for each method and discussed them at the end of this paper.

Nonparmetric Method for Identifying Effective and Safe Doses using Placement (유효하고 안전한 용량 결정에 위치를 이용한 비모수적 방법)

  • Kim, Sunhye;Kim, Dongjae
    • The Korean Journal of Applied Statistics
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    • v.27 no.7
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    • pp.1197-1205
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    • 2014
  • Typical clinical dose development studies consist of the comparison of several doses of a drug with a placebo. The primary interest is to find therapeutic window that satisfying both efficacy and safety. In this paper, we propose nonparametric method for identifying effective and safe doses in linear placement using score function. The Monte Carlo simulation is adapted to estimate the power and the family-wise error rate(FWE) of proposed procedure are compared with previous methods.