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USP44 Promotes the Tumorigenesis of Prostate Cancer Cells through EZH2 Protein Stabilization

  • Park, Jae Min;Lee, Jae Eun;Park, Chan Mi;Kim, Jung Hwa
    • Molecules and Cells
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    • v.42 no.1
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    • pp.17-27
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    • 2019
  • Ubiquitin-specific protease 44 (USP44) has been implicated in tumor progression and metastasis across various tumors. However, the function of USP44 in prostate cancers and regulatory mechanism of histone-modifying enzymes by USP44 in tumors is not well-understood. Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. We showed that EZH2 is a novel target of USP44 and that the protein stability of EZH2 is upregulated by USP44-mediated deubiquitination. In USP44 knockdown prostate cancer cells, the EZH2 protein level and its gene silencing activity were decreased. Furthermore, USP44 knockdown inhibited the tumorigenic characteristics and cancer stem cell-like behaviors of prostate cancer cells. Inhibition of tumorigenesis caused by USP44 knockdown was recovered by ectopic introduction of EZH2. Additionally, USP44 regulates the protein stability of oncogenic EZH2 mutants. Taken together, our results suggest that USP44 promotes the tumorigenesis of prostate cancer cells partly by stabilizing EZH2 and that USP44 is a viable therapeutic target for treating EZH2-dependent cancers.

Circulating HOTAIR LncRNA Is Potentially Up-regulated in Coronary Artery Disease

  • Avazpour, Niloofar;Hajjari, Mohammadreza;Yazdankhah, Saeed;Sahni, Azita;Foroughmand, Ali Mohammad
    • Genomics & Informatics
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    • v.16 no.4
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    • pp.25.1-25.5
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    • 2018
  • Coronary artery disease (CAD) is one of the leading causes of death and disability all around the world. Recent studies have revealed that aberrantly regulated long non-coding RNA (lncRNA) as one of the main classes of cellular transcript plays a key regulatory role in transcriptional and epigenetic pathways. Recent reports have demonstrated that circulating lncRNAs in the blood can be potential biomarkers for CAD. HOTAIR is one of the most cited lncRNAs with a critical role in the initiation and progression of the gene expression regulation. Recent research on the role of the HOTAIR in cardiovascular disease lays the basis for the development of new studies considering this lncRNA as a potential biomarker and therapeutic target in CAD. In this study, we aimed to compare the expression of HOTAIR lncRNA in the blood samples of patients with CAD and control samples. The expression level was examined by semi-quantitative reverse transcriptase polymerase chain reaction technique. Our data shows that expression of HOTAIR is up-regulated in blood samples of patients with CAD.

High NDRG3 expression facilitates HCC metastasis by promoting nuclear translocation of β-catenin

  • Shi, JiKui;Zheng, HongZhen;Yuan, LingYan
    • BMB Reports
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    • v.52 no.7
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    • pp.451-456
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    • 2019
  • NDRG1 has been reported to exert pivotal roles in tumor progression and metastasis via Wnt/${\beta}$-catenin signaling pathway. However, little is known about the role of NDRG3 in hepatocarcinogenesis despite its classification in the same subfamily of NDRG1. The present study was aimed to characterize the expression pattern and understand the biological roles of NDRG3 in hepatocarcinogenesis, as a means to exploit its therapeutic potential. It was observed that NDRG3 was up-regulated in HCC tissues and higher NDRG3 expression was associated with significantly shorter overall survival. Furthermore, a lower level of NDRG3 exhibited marked positive correlation with metastasis-free survival. In vitro and in vivo experiments revealed that knock-down of NDRG3 inhibits HCC metastasis and angiogenesis. We further demonstrated that activation of WNT/${\beta}$-catenin signaling and enhanced CSC-like properties were responsible for NDRG3-mediated promoting effect on HCC. In conclusion, the principal findings demonstrated that high NDRG3 expression facilitates HCC metastasis via regulating the turnover of ${\beta}$-catenin, as well as provides a potential therapeutic target for future therapeutic interventions.

A Model of Military Helicopter Pilot Scheduling (군용 헬리콥터 조종사 스케줄링 모형)

  • Kim, Joo An;Lee, Moon Gul
    • Journal of Korean Society of Industrial and Systems Engineering
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    • v.43 no.4
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    • pp.150-160
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    • 2020
  • In this paper, we introduce a pilot's scheduling model which is able to maintain and balance their capabilities for each relevant skill level in military helicopter squadron. Flight scheduler has to consider many factors related pilot's flight information and spends a lot of times and efforts for flight planning without scientific process depending on his/her own capability and experience. This model reflected overall characteristics that include pilot's progression by basis monthly and cumulative flight hours, operational recent flight data and quickly find out a pinpoint areas of concern with respect to their mission subjects etc. There also include essential several constraints, such as personnel qualifications, and Army helicopter training policy's constraints such as regulations and guidelines. We presented binary Integer Programming (IP) mathematical formulation for optimization and demonstrated its effectiveness by comparisons of real schedule versus model's solution to several cases experimental scenarios and greedy random simulation model. The model made the schedule in less than 30 minutes, including the data preprocessing process, and the results of the allocation were more equal than the actual one. This makes it possible to reduce the workload of the scheduler and effectively manages the pilot's skills. We expect to set up and improve better flight planning and combat readiness in Korea Army aviation.

The role of the voltage-gated potassium channel, Kv2.1 in prostate cancer cell migration

  • Park, Hyun Woo;Song, Min Seok;Sim, Hun Ju;Ryu, Pan Dong;Lee, So Yeong
    • BMB Reports
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    • v.54 no.2
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    • pp.130-135
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    • 2021
  • Voltage-gated potassium (Kv) channels are involved in many important cellular functions and play pivotal roles in cancer progression. The expression level of Kv2.1 was observed to be higher in the highly metastatic prostate cancer cells (PC-3), specifically in their membrane, than in immortalized prostate cells (WPMY-1 cells) and comparatively less metastatic prostate cancer cells (LNCaP and DU145 cells). However, Kv2.1 expression was significantly decreased when the cells were treated with antioxidants, such as N-acetylcysteine or ascorbic acid, implying that the highly expressed Kv2.1 could detect reactive oxygen species (ROS) in malignant prostate cancer cells. In addition, the blockade of Kv2.1 with stromatoxin-1 or siRNA targeting Kv2.1 significantly inhibited the migration of malignant prostate cancer cells. Our results suggested that Kv2.1 plays an important role as a ROS sensor and that it is a promising therapeutic molecular target in metastasis of prostate cancer.

Factors Related to High Risk Drinking in Adult Drinkers by Age Group (연령군별 성인 음주자의 고위험음주 관련 요인)

  • Lee, Eun Sook;Seo, Yeong-Mi
    • Journal of East-West Nursing Research
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    • v.27 no.1
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    • pp.51-60
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    • 2021
  • Purpose: The purpose of this study was to identify factors associated with high risk drinking in adults. Methods: Multi-variate logistic regression was used to analyze the data of 15,949 adults age 19 years or older from the sixth (2013-2015) Korea National Health and Nutrition Examination Survey. Results: Factors associated with high risk drinking included education level, employment and smoking status among the age group of 19-39. In the 40-59 year age group, the associated factors were gender, employment, smoking, obesity, and depressive mood. In the over 60 year age group, related factors included gender, employment, smoking, abdominal obesity, and subjective health status. Conclusion: The result of this study suggests that early risk factor screening may be helpful to avoid the progression to high-risk drinking. An individualized approach for each age group can be used as a preventive measure.

Idiopathic multicentric Castleman disease presenting progressive reticular honeycomb infiltration of lung and immunoglobulin G and immunoglobulin G4 dominant hypergammaglobulinemia: a case report

  • Kim, Hyun-Je;Hong, Young-Hoon
    • Journal of Yeungnam Medical Science
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    • v.39 no.2
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    • pp.153-160
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    • 2022
  • Multicentric Castleman disease (MCD) is an uncommon systemic lymphoproliferative disorder that may cause multiple organ damage. Castleman disease-associated diffuse parenchymal lung disease (DPLD) has not been well studied. A 32-year-old man was referred to our hospital for progressive generalized weakness, light-headedness, and dyspnea on exertion for more than one year. Laboratory evaluations showed profound anemia, an elevated erythrocyte sedimentation rate, and an increased C-reactive protein level with polyclonal hypergammaglobulinemia. Chest radiography, computed tomography (CT), and positron emission tomography-CT scan demonstrated diffuse lung infiltration with multiple cystic lesions and multiple lymphadenopathy. In addition to these clinical laboratory findings, bone marrow, lung, and lymph node biopsies confirmed the diagnosis of idiopathic MCD (iMCD). Siltuximab, an interleukin-6 inhibitor, and glucocorticoid therapy were initiated. The patient has been tolerating the treatment well and had no disease progression or any complications in 4 years. Herein, we report this case of human herpesvirus-8-negative iMCD-associated DPLD accompanied by multiple cystic lesions, multiple lymphadenopathy, and polyclonal hypergammaglobulinemia with elevated immunoglobulin G (IgG) and IgG4 levels. We recommend a close evaluation of MCD in cases of DPLD with hypergammaglobulinemia.

Emerging role of anti-proliferative protein BTG1 and BTG2

  • Kim, Sang Hyeon;Jung, In Ryeong;Hwang, Soo Seok
    • BMB Reports
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    • v.55 no.8
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    • pp.380-388
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    • 2022
  • The B cell translocation gene 1 (BTG1) and BTG2 play a key role in a wide range of cellular activities including proliferation, apoptosis, and cell growth via modulating a variety of central biological steps such as transcription, post-transcriptional, and translation. BTG1 and BTG2 have been identified by genomic profiling of B-cell leukemia and diverse lymphoma types where both genes are commonly mutated, implying that they serve as tumor suppressors. Furthermore, a low expression level of BTG1 or BTG2 in solid tumors is frequently associated with malignant progression and poor treatment outcomes. As physiological aspects, BTG1 and BTG2 have been discovered to play a critical function in regulating quiescence in hematopoietic lineage such as Hematopoietic stem cells (HSCs) and naive and memory T cells, highlighting their novel role in maintaining the quiescent state. Taken together, emerging evidence from the recent studies suggests that BTG1 and BTG2 play a central anti-proliferative role in various tissues and cells, indicating their potential as targets for innovative therapeutics.

Molecular Tension Probes to Quantify Cell-Generated Mechanical Forces

  • Baek, Kyung Yup;Kim, Seohyun;Koh, Hye Ran
    • Molecules and Cells
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    • v.45 no.1
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    • pp.26-32
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    • 2022
  • Living cells generate, sense, and respond to mechanical forces through their interaction with neighboring cells or extracellular matrix, thereby regulating diverse cellular processes such as growth, motility, differentiation, and immune responses. Dysregulation of mechanosensitive signaling pathways is found associated with the development and progression of various diseases such as cancer. Yet, little is known about the mechanisms behind mechano-regulation, largely due to the limited availability of tools to study it at the molecular level. The recent development of molecular tension probes allows measurement of cellular forces exerted by single ligand-receptor interaction, which has helped in revealing the hitherto unknown mechanistic details of various mechanosensitive processes in living cells. Here, we provide an introductory overview of two methods based on molecular tension probes, tension gauge tether (TGT), and molecular tension fluorescence microscopy (MTFM). TGT utilizes the irreversible rupture of double-stranded DNA tether upon application of force in the piconewton (pN) range, whereas MTFM utilizes the reversible extension of molecular springs such as polymer or single-stranded DNA hairpin under applied pN forces. Specifically, the underlying principle of how molecular tension probes measure cell-generated mechanical forces and their applications to mechanosensitive biological processes are described.

KM-based Treatment of Viral Hepatitis A accompanied with Pancreatitis: A case report

  • Son, Chang-Gue
    • The Journal of Korean Medicine
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    • v.41 no.4
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    • pp.106-111
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    • 2020
  • Objectives: Hepatitis A is a typical acute hepatitis caused by hepatovirus, and then most patients recover easily without progression to chronic condition. However, certain cases have the risk of severe symptoms or even death. This case report presented a hepatitis A accompanied with pancreatitis, which had been completely recovered in a Korean medicine hospital. Case presentation: A 38-year woman had felt the malaise, mild chilling, muscle pain and abdominal discomfort for 10 days, which led her visit doctors and took anti-pyretic analgesics and digestants. The symptoms, especially epigastric pain and fatigue, became worse, and then she hospitalized in a Korean medicine hospital. Based on the drastic elevations of hepatic enzymes (aspartate transaminase 1,604 IU/L and alanine transaminase 2,825IU/L) with an anti-HAV IgM positive, she was diagnosed with hepatitis A. After bed rest and herbal drug treatment (CGX and Innae-Tang) for 5 days, the laboratory abnormalities and subjective symptoms had been improved gradually, except the upper gastric discomfort and pain. Those symptoms had anticipated the comorbidity with HAV-induced pancreatitis, supported by the high level of serum lipase release. Another 5-day hospitalized treatment improved all subjective symptoms and then the laboratory results were completely normalized including detection of anti-HAV IgG within 15 days after discharge. Conclusion: This study presented a typical hepatitis A accompanied with pancreatitis, which should be considered in diagnosis and management of hepatitis A.