• Title/Summary/Keyword: cancer targeting

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Nuclear localization signal domain of HDAC3 is necessary and sufficient for the expression regulation of MDR1

  • Park, Hyunmi;Kim, Youngmi;Park, Deokbum;Jeoung, Dooil
    • BMB Reports
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    • v.47 no.6
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    • pp.342-347
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    • 2014
  • Histone acetylation/deacetylation has been known to be associated with the transcriptional regulation of various genes. The role of histone deacetylase-3 in the expression regulation of MDR1 was investigated. The expression level of HDAC3 showed an inverse relationship with the expression level of MDR1. Wild-type HDAC3, but not catalytic mutant $HDAC3^{S424A}$, negatively regulated the expression of MDR1. Wild-type HDAC3, but not catalytic mutant $HDAC3^{S424A}$, showed binding to the promoter sequences of HDAC3. HDAC3 regulated the expression level, and the binding of Ac-$H3^{K9/14}$ and Ac-$H4^{K16}$ around the MDR1 promoter sequences. The nuclear localization signal domain of HDAC3 was necessary, and sufficient for the binding of HDAC3 to the MDR1 promoter sequences and for conferring sensitivity to microtubule-targeting drugs.

Prognostic factors and treatment of pediatric acute lymphoblastic leukemia

  • Lee, Jae Wook;Cho, Bin
    • Clinical and Experimental Pediatrics
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    • v.60 no.5
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    • pp.129-137
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    • 2017
  • The event-free survival (EFS) for pediatric acute lymphoblastic leukemia (ALL) has shown remarkable improvement in the past several decades. In Korea also, a recent study showed 10-year EFS of 78.5%. Much of the improved outcome for pediatric ALL stems from the accurate identification of prognostic factors, the designation of risk group based on these factors, and treatment of appropriate duration and intensity according to risk group, done within the setting of cooperative clinical trials. The schema of first-line therapy for ALL remains mostly unchanged, although many groups have now reported on the elimination of cranial irradiation in all patients with low rates of central nervous system relapse. Specific high risk subgroups, such as Philadelphia chromosome-positive (Ph+) ALL and infant ALL continue to have significantly lower survival than other ALL patients. The introduction of tyrosine kinase inhibitors into therapy has led to enhanced outcome for Ph+ ALL patients. Infant ALL patients, particularly those with MLL rearrangements, continue to have poor outcome, despite treatment intensification including allogeneic hematopoietic cell transplantation. Relapsed ALL is a leading cause of mortality in pediatric cancer. Recent advances in immunotherapy targeting the CD19 of the ALL blast have shown remarkable efficacy in some of these relapsed and refractory patients. With improved survival, much of the current focus is on decreasing the long-term toxicities of treatment.

Myosin VI contributes to malignant proliferation of human glioma cells

  • Xu, Rong;Fang, Xu-hao;Zhong, Ping
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.2
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    • pp.139-145
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    • 2016
  • Previously characterized as a backward motor, myosin VI (MYO6), which belongs to myosin family, moves toward the minus end of the actin track, a direction opposite to all other known myosin members. Recent researches have illuminated the role of MYO6 in human cancers, particularly in prostate cancer. However, the role of MYO6 in glioma has not yet been determined. In this study, to explore the role of MYO6 in human glioma, lentivirus-delivered short hairpin RNA (shRNA) targeting MYO6 was designed to stably down-regulate its endogenous expression in glioblastoma cells U251. Knockdown of MYO6 significantly inhibited viability and proliferation of U251 cells in vitro. Moreover, the cell cycle of U251 cells was arrested at G0/G1 phase with the absence of MYO6, which could contribute to the suppression of cell proliferation. In conclusion, we firstly identified the crucial involvement of MYO6 in human glioma. The inhibition of MYO6 by shRNA might be a potential therapeutic method in human glioma.

Factors Influencing HPV-related Infection Preventive Behavioral Intention among Female University Students (여대생의 인유두종 바이러스(HPV) 관련 감염예방행위의도 영향요인)

  • Kim, Sun Hwa;Sung, Mi-Hae
    • Women's Health Nursing
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    • v.23 no.2
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    • pp.126-134
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    • 2017
  • Purpose: The purpose of this study was to identify impacts of HPV-related knowledge, attitude to HPV vaccination, and health beliefs on infection preventive behavioral intention targeting female university students. Methods: With correlational survey design, subjects of this study were 120 female students at universities located in B metropolitan city and G city. A total sample agreed to participate in the study. Data were analyzed using descriptive statistics, t-test, ANOVA, correlation, and stepwise multiple regression. Results: Attitude to HPV vaccination, experience of smoking, and HPV-related health beliefs were significant factors influencing the HPV-related infection preventive behavioral intention. These factors accounted for 19.0% of the HPV-related infection preventive behavioral intention. Conclusion: The most significant factor for HPV infection prevention was the attitude to HPV vaccination. These findings may be useful to develop strategies to improve the HPV infection preventive behavioral intention of the female university students who have a high risk of the HPV infection.

Development of an Evidence-based Nursing Process System to Improve Clinical Decision Making with Colorectal Cancer Nursing Diagnosis (임상의사결정 향상을 위한 근거 기반 간호과정 시스템 개발-대장암 간호진단을 중심으로-)

  • Park, Hyun Sang;Cho, Hune;Kim, Hwa Sun
    • Journal of Korea Multimedia Society
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    • v.19 no.7
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    • pp.1197-1207
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    • 2016
  • The purpose of this study was to develop an evidence-based Nursing Process System on Nursing Diagnosis, Nursing Outcomes, and Nursing Interventions Classification targeting nurse students. We use standard classification-focused research data on the basis of Nursing Diagnosis Classification established by NANDA (North American Nursing Diagnosis Association), NOC (Nursing Outcomes Classification) and NIC (Nursing Interventions Classification) mainly developed by Iowa Sate University. The existing research methods are difficult to be applied the consistent nursing process, since such methods need to repeatedly enter the same nursing process without systematic guidelines. But, this study was coded data of standardized nursing process in accordance with the 10 clinical condition in order to implement the nursing process macro, and developed a system that reflects the needs of nursing educators. Therefore, nurse students can improve clinical decision-making ability, and naturally learn the nursing process through a system developed.

RNA Binding Protein-Mediated Post-Transcriptional Gene Regulation in Medulloblastoma

  • Bish, Rebecca;Vogel, Christine
    • Molecules and Cells
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    • v.37 no.5
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    • pp.357-364
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    • 2014
  • Medulloblastoma, the most common malignant brain tumor in children, is a disease whose mechanisms are now beginning to be uncovered by high-throughput studies of somatic mutations, mRNA expression patterns, and epigenetic profiles of patient tumors. One emerging theme from studies that sequenced the tumor genomes of large cohorts of medulloblastoma patients is frequent mutation of RNA binding proteins. Proteins which bind multiple RNA targets can act as master regulators of gene expression at the post-transcriptional level to co-ordinate cellular processes and alter the phenotype of the cell. Identification of the target genes of RNA binding proteins may highlight essential pathways of medulloblastomagenesis that cannot be detected by study of transcriptomics alone. Furthermore, a subset of RNA binding proteins are attractive drug targets. For example, compounds that are under development as anti-viral targets due to their ability to inhibit RNA helicases could also be tested in novel approaches to medulloblastoma therapy by targeting key RNA binding proteins. In this review, we discuss a number of RNA binding proteins, including Musashi1 (MSI1), DEAD (Asp-Glu-Ala-Asp) box helicase 3 X-linked (DDX3X), DDX31, and cell division cycle and apoptosis regulator 1 (CCAR1), which play potentially critical roles in the growth and/or maintenance of medulloblastoma.

Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells

  • Park, Seulki;Kim, Kidae;Haam, Keeok;Ban, Hyun Seung;Kim, Jung-Ae;Park, Byoung Chul;Park, Sung Goo;Kim, Sunhong;Kim, Jeong-Hoon
    • BMB Reports
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    • v.54 no.6
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    • pp.305-310
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    • 2021
  • Cereblon (CRBN) is a multi-functional protein that acts as a substrate receptor of the E3 ligase complex and a molecular chaperone. While CRBN is proposed to function in mitochondria, its specific roles are yet to be established. Here, we showed that knockdown of CRBN triggers oxidative stress and calcium overload in mitochondria, leading to disruption of mitochondrial membrane potential. Notably, long-term CRBN depletion using PROteolysis TArgeting Chimera (PROTAC) induced irreversible mitochondrial dysfunction, resulting in cell death. Our collective findings indicate that CRBN is required for mitochondrial homeostasis in cells.

Human Endogenous Retroviruses as Gene Expression Regulators: Insights from Animal Models into Human Diseases

  • Durnaoglu, Serpen;Lee, Sun-Kyung;Ahnn, Joohong
    • Molecules and Cells
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    • v.44 no.12
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    • pp.861-878
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    • 2021
  • The human genome contains many retroviral elements called human endogenous retroviruses (HERVs), resulting from the integration of retroviruses throughout evolution. HERVs once were considered inactive junk because they are not replication-competent, primarily localized in the heterochromatin, and silenced by methylation. But HERVs are now clearly shown to actively regulate gene expression in various physiological and pathological conditions such as developmental processes, immune regulation, cancers, autoimmune diseases, and neurological disorders. Recent studies report that HERVs are activated in patients suffering from coronavirus disease 2019 (COVID-19), the current pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. In this review, we describe internal and external factors that influence HERV activities. We also present evidence showing the gene regulatory activity of HERV LTRs (long terminal repeats) in model organisms such as mice, rats, zebrafish, and invertebrate models of worms and flies. Finally, we discuss several molecular and cellular pathways involving various transcription factors and receptors, through which HERVs affect downstream cellular and physiological events such as epigenetic modifications, calcium influx, protein phosphorylation, and cytokine release. Understanding how HERVs participate in various physiological and pathological processes will help develop a strategy to generate effective therapeutic approaches targeting HERVs.

Discovery of Anticancer Activity of Amentoflavone on Esophageal Squamous Cell Carcinoma: Bioinformatics, Structure-Based Virtual Screening, and Biological Evaluation

  • Chen, Lei;Fang, Bo;Qiao, Liman;Zheng, Yihui
    • Journal of Microbiology and Biotechnology
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    • v.32 no.6
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    • pp.718-729
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    • 2022
  • Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy with poor prognosis. Here, due to the necessity for exploring potential therapies against ESCC, we obtained the gene expression data on ESCC from the TCGA and GEO databases. Venn diagram analysis was applied to identify common targets. The protein-protein interaction network was constructed by Cytoscape software, and the hub targets were extracted from the network via cytoHubba. The potential hub nodes as drug targets were found by pharmacophore-based virtual screening and molecular modeling, and the antitumor activity was evaluated through in vitro studies. A total of 364 differentially expressed genes (DEGs) in ESCC were identified. Pathway enrichment analyses suggested that most DEGs were mainly involved in the cell cycle. Three hub targets were retrieved, including CENPF, CCNA2 (cyclin A), and CCNB1 (cyclin B1), which were highly expressed in esophageal cancer and associated with prognosis. Moreover, amentoflavone, a promising drug candidate found by pharmacophore-based virtual screening, showed antiproliferative and proapoptotic effects and induced G1 in esophageal squamous carcinoma cells. Taken together, our findings suggested that amentoflavone could be a potential cell cycle inhibitor targeting cyclin B1, and is therefore expected to serve as a great therapeutic agent for treating esophageal squamous cell carcinoma.

In silico investigation of Panax ginseng lead compounds against COVID-19 associated platelet activation and thromboembolism

  • Yixian Quah;Yuan Yee Lee;Seung-Jin Lee;Sung Dae Kim;Man Hee Rhee;Seung-Chun Park
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.283-290
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    • 2023
  • Hypercoagulability is frequently observed in patients with severe coronavirus disease-2019 (COVID-19). Platelets are a favorable target for effectively treating hypercoagulability in COVID-19 patients as platelet hyperactivity has also been observed. It is difficult to develop a treatment for COVID-19 that will be effective against all variants and the use of antivirals may not be fully effective against COVID-19 as activated platelets have been detected in patients with COVID-19. Therefore, patients with less severe side effects often turn toward natural remedies. Numerous phytochemicals are being investigated for their potential to treat a variety of illnesses, including cancer and bacterial and viral infections. Natural products have been used to alleviate COVID-19 symptoms. Panax ginseng has potential for managing cardiovascular diseases and could be a treatment for COVID-19 by targeting the coagulation cascade and platelet activation. Using molecular docking, we analyzed the interactions of bioactive chemicals in P. ginseng with important proteins and receptors involved in platelet activation. Furthermore, the SwissADME online tool was used to calculate the pharmacokinetics and drug-likeness properties of the lead compounds of P. ginseng. Dianthramine, deoxyharrtingtonine, and suchilactone were determined to have favorable pharmacokinetic profiles.