• Title/Summary/Keyword: therapeutic evidence

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A Criticism Regarding the Medical Rationale of Nucleoplasty Studies for Internal Disc Disruption (수핵성형술(Nucleoplasty)을 이용한 디스크 내장증(Internal Disc Disruption)의 치료 연구들의 의학적 논거에 대한 비판)

  • Hong, Youngki
    • The Journal of the Korea Contents Association
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    • v.22 no.9
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    • pp.570-582
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    • 2022
  • Nucleoplasty is a type of percutaneous disc decompression that has been developed to treat herniated intervertebral discs. Currently, in some clinics, researchers have also applied this procedure to patients with internal disc disruption, apart from the originally intended usage on herniated intervertebral discs. The purpose of this study is to evaluate the feasibility of this extended use based on medical logic. To achieve this, the author analyzed case studies on performing nucleoplasty on patients with internal disc disruption. The main points of the analysis are, first, the validity of the treatment evidence presented by the researchers and, second, the relevance of the patient selection criteria. As a result, it is judged that the therapeutic rationale of existing papers applying nucleoplasty to the treatment of internal disc disruption is unclear or inconsistent with general medical logic, and in the process of patient screening, discs that may be deemed inappropriate for percutaneous decompression are included. Therefore, the author believes that existing studies applying nucleoplasty to the treatment of internal disc disruption have the nature of somewhat adventurous experiments that are unnecessary or can cause potential side effects. In order to uphold patients' rights and improve the completeness of the study in the research process on this topic, the author thinks that it is essential to establish clearer therapeutic evidence than the current level of understanding and to have an elaborate patient screening process based on it.

Clinical Practice Guidelines for Gastric Cancer in Korea: An Evidence-Based Approach

  • Lee, Jun Haeng;Kim, Jae G.;Jung, Hye-Kyung;Kim, Jung Hoon;Jeong, Woo Kyoung;Jeon, Tae Joo;Kim, Joon Mee;Kim, Young Il;Ryu, Keun Won;Kong, Seong-Ho;Kim, Hyoung-Il;Jung, Hwoon-Yong;Kim, Yong Sik;Zang, Dae Young;Cho, Jae Yong;Park, Joon Oh;Lim, Do Hoon;Jung, Eun Sun;Ahn, Hyeong Sik;Kim, Hyun Jung
    • Journal of Gastric Cancer
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    • v.14 no.2
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    • pp.87-104
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    • 2014
  • Although gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to those in western countries. However, there are currently no Korean multidisciplinary guidelines for gastric cancer. Experts from related societies developed guidelines de novo to meet Korean circumstances and requirements, including 23 recommendation statements for diagnosis (n=9) and treatment (n=14) based on relevant key questions. The quality of the evidence was rated according to the GRADE evidence evaluation framework: the evidence levels were based on a systematic review of the literature, and the recommendation grades were classified as either strong or weak. The applicability of the guidelines was considered to meet patients' view and preferences in the context of Korea. The topics of the guidelines cover diagnostic modalities (endoscopy, endoscopic ultrasound, and radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, and radiotherapy), and pathologic evaluation. An external review of the guidelines was conducted during the finalization phase.

A Systematic Review on Intervention to Improve Executive Function in Stroke Patients (뇌졸중 환자 집행 기능 향상을 위한 중재에 대한 체계적 고찰)

  • Ko, Seok-Beom;Kim, Moon-Young;Oh, Yun-Taek
    • Therapeutic Science for Rehabilitation
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    • v.4 no.2
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    • pp.33-50
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    • 2015
  • Objective : This study was conducted to determine various interventions in accordance with the recovery and cognitive processes in order to improve executive function in stroke patients through a systematic review. Methods : The literature search focused on Level I-IV studies published between January 1996 and April 2015 for 20 years in electronic databases(e.g. MEDLINE, SCOPUS, RISS). The keyword search terms were 'Stroke', 'Executive function', 'Executive function deficit', 'Occupational therapy', 'Rehabilitation', 'Remedial', 'Compensatory' and 'Education'. Result : A total of 13 articles were appraised using the hierarchy of levels of evidence-based practice and 6 Level I evidence articles, 1 Level II articles, 2 Level III articles and 4 Level IV articles. Each intervention improved executive function but was different in degree of generalization. Conclusion : Through this systematic review, we found that there are a variety of applied interventions improving executive function in stroke patients and are different in effect depending on methods of interventions. This study provided evidences to occupational therapists for the clinical practice of interventions to improve executive function in stroke patients.

Recent Understanding in Particular Matter-Mediated Aging and Age-Related Diseases (미세먼지에 의한 노화 및 노화 관련 질병에 대한 최근 연구 동향)

  • EunJin Bang;Yung Hyun Choi
    • Journal of Life Science
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    • v.34 no.1
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    • pp.68-77
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    • 2024
  • Airborne particulate matter (PM) is an environmentally hazardous pollutant that originates from various sources. PM is comprised of solid particles and liquid droplets of diverse composition and size. Hazardous chemical compositions of PM include elemental and organic carbon, organic compounds, biological compounds and metals. Upon acute and chronic PM exposure, toxic contaminants enter and accumulate within physiological systems and prompt cell structure changes accompanied with intracellular endoplasmic reticulum stress, mitochondrial dysfunction, oxidative stress, inflammation, lipid accumulation, and cell cycle arrest. Ultimately, these cellular response leads to the development of key characteristics of aging. In addition, PM internalization enhances autophagy reflux and lysosomal dysfunction, which is involved in cell aging. Previous studies have emphasized a positive association between PM and increased mortality or decreased lifespan, although these are evidenced mostly by observational studies. Direct evidence of the link between PM and aging is still limited. This review evaluates the evidence from not only observational studies but also in vitro and in vivo evidence of PM on aging progression and age-related diseases development. This evidence is based on age-associated cellular changes including endoplasmic reticulum stress, mitochondrial dysfunction, oxidative stress, inflammation, adipose accumulation, autophagy, which strengthen the association between PM exposure and aging. Understanding the underlying cellular responses under PM may allow for the development of new therapeutic targets for PM-induced aging.

High Affinity Pharmacological Profiling of Dual Inhibitors Targeting RET and VEGFR2 in Inhibition of Kinase and Angiogeneis Events in Medullary Thyroid Carcinoma

  • Dunna, Nageswara Rao;Kandula, Venkatesh;Girdhar, Amandeep;Pudutha, Amareshwari;Hussain, Tajamul;Bandaru, Srinivas;Nayarisseri, Anuraj
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.7089-7095
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    • 2015
  • Clinical evidence shows that dual inhibition of kinases as well angiogenesis provides ideal therapeutic option in the treatment of medullary thyroid carcinoma (MTC) than inhibiting either of these with the events separately. Although treatment with dual inhibitors has shown good clinical responses in patients with MTC, it has been associated with serious side effects. Some inhibitors are active agents for both angiogenesis or kinase activity. Owing to narrow therapeutic window of established inhibitors, the present study aims to identify high affinity dual inhibitors targeting RET and VEGFR2 respectively for kinase and angiogenesis activity. Established inhibitors like Vandetanib, Cabozantinib, Motesanib, PP121, RAF265 and Sunitinib served as query parent compounds for identification of structurally similar compounds by Tanimoto-based similarity searching with a threshold of 95% against the PubChem database. All the parent inhibitors and respective similar compounds were docked against RET and VEGFR2 in order to retrieve high affinity compounds with these two proteins. AGN-PC-0CUK9P PubCID: 59320403 a compound related to PPI21 showed almost equal affinity for RET and VEGFR2 and unlike other screened compounds with no apparent bias for either of the receptors. Further, AGNPC- 0CUK9P demonstrated appreciable interaction with both RET and VEGFR2 and superior kinase activity in addition to showed optimal ADMET properties and pharmacophore features. From our in silico investigation we suggest AGN-PC-0CUK9P as a superior dual inhibitor targeting RET and VEGFR2 with high efficacy which should be proposed for pharmacodynamic and pharmacokinetic studies for improved treatment of MTC.

Sensitization of Cervical Carcinoma Cells to Paclitaxel by an IPP5 Active Mutant

  • Zeng, Qi-Yan;Huang, Yu;Zeng, Lin-Jie;Huang, Min;Huang, Yong-Qi;Zhu, Qi-Fang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8337-8343
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    • 2014
  • Paclitaxel is one of the best anticancer agents that has been isolated from plants, but its major disadvantage is its dose-limiting toxicity. In this study, we obtained evidence that the active mutant IPP5 ($8-60hIPP5^m$), the latest member of the inhibitory molecules for protein phosphatase 1, sensitizes human cervix carcinoma cells HeLa more efficiently to the therapeutic effects of paclitaxel. The combination of $8-60hIPP5^m$ with paclitaxel augmented anticancer effects as compared to paclitaxel alone as evidenced by reduced DNA synthesis and increased cytotoxicity in HeLa cells. Furthermore, our results revealed that $8-60hIPP5^m$ enhances paclitaxel-induced G2/M arrest and apoptosis, and augments paclitaxel-induced activation of caspases and release of cytochrome C. Evaluation of signaling pathways indicated that this synergism was in part related to downregulation of NF-${\kappa}B$ activation and serine/threonine kinase Akt pathways. We noted that $8-60hIPP5^m$ downregulated the paclitaxel-induced NF-${\kappa}B$ activation, $I{\kappa}B{\alpha}$ degradation, PI3-K activity and phosphorylation of the serine/threonine kinase Akt, a survival signal which in many instances is regulated by NF-${\kappa}B$. Together, our observations indicate that paclitaxel in combination with $8-60hIPP5^m$ may provide a therapeutic advantage for the treatment of human cervical carcinoma.

Effects of Saenghyul-dan (SHD) on the Myelosuppression Induced by 5-Fluorouracil

  • Lee, Gi-Joon;Son, Chang-Gue;Lee, Yeon-Weol;Lee, Nam-Heon;Yun, Dam-Hee;Yoo, Hwa-Seung;Cho, Chong-Kwan;Cho, Jung-Hyo
    • The Journal of Korean Medicine
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    • v.27 no.4
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    • pp.62-73
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    • 2006
  • Objective : This study aimed to investigate the effect of SHD on myelosuppression using an animal model for therapeutic evidence supporting clinical positive results. Methods : After determining the optimal concentration of 5-FU as 300 mg/kg for developing the mouse model, ICR mice or BALB/c mice were administered with SHD, and several blood parameters, including hematopoietic cytokines, colony forming activity and histological findings, were examined to evaluate the effects. Results : SHD restored the WBC and hemoglobin, and showed effects on maintaining body weight, producing GM-CSF and IL-3 and stem cell colony forming activity in accordance with histological relative entirety on bone marrow. Conclusion : SHD is an herbal drug having therapeutic effects on myelosuppression. Thus, it could be prescribed to cancer patients undergoing chemo-therapies or radio-therapies in the process of cancer treatment.

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Superoxide dismutase 3 protects mesenchymal stem cells through enhanced autophagy and regulation of FoxO3a trafficking

  • Agrahari, Gaurav;Sah, Shyam Kishor;Kim, Tae-Yoon
    • BMB Reports
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    • v.51 no.7
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    • pp.344-349
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    • 2018
  • Therapeutic applications of mesenchymal stem cells (MSCs) are limited due to their early death within the first few days of transplantation. Therefore, to improve the efficacy of cell-based therapies, it is necessary to manipulate MSCs so that they can resist various stresses imposed by the microenvironment. Moreover, the role of superoxide dismutase 3 (SOD3) in regulating such survival under different stress conditions remain elusive. In this study, we overexpressed SOD3 in MSCs (SOD3-MSCs) and evaluated its effect under serum starvation conditions. Nutritional limitation can decrease the survival rate of transplanted MSCs and thus can reduce their efficacy during therapy. Interestingly, we found that SOD3-MSCs exhibited reduced reactive oxygen species levels and greater survival rates than normal MSCs under serum-deprived conditions. In addition, overexpression of SOD3 attenuated starvation-induced apoptosis with increased autophagy in MSCs. Moreover, we have demonstrated that SOD3 protects MSCs against the negative effects of serum deprivation via modulation of AMP-activated protein kinase/sirtulin 1, extracellular signal-regulated kinase activation, and promoted Forkhead box O3a trafficking to the nucleus. Taken together, these results demonstrate that SOD3 promotes MSCs survival and add further evidence to the concept that SOD3-MSCs may be a potential therapeutic agent with better outcomes than normal MSCs for various diseases involving oxidative stress and compromised MSCs survival during therapy.

Selonsertib Inhibits Liver Fibrosis via Downregulation of ASK1/MAPK Pathway of Hepatic Stellate Cells

  • Yoon, Young-Chan;Fang, Zhenghuan;Lee, Ji Eun;Park, Jung Hee;Ryu, Ji-Kan;Jung, Kyung Hee;Hong, Soon-Sun
    • Biomolecules & Therapeutics
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    • v.28 no.6
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    • pp.527-536
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    • 2020
  • Liver fibrosis constitutes a significant health problem worldwide due to its rapidly increasing prevalence and the absence of specific and effective treatments. Growing evidence suggests that apoptosis-signal regulating kinase 1 (ASK1) is activated in oxidative stress, which causes hepatic inflammation and apoptosis, leading to liver fibrogenesis through a mitogen-activated protein kinase (MAPK) downstream signals. In this study, we investigated whether selonsertib, a selective inhibitor of ASK1, shows therapeutic efficacy for liver fibrosis, and elucidated its mechanism of action in vivo and in vitro. As a result, selonsertib strongly suppressed the growth and proliferation of hepatic stellate cells (HSCs) and induced apoptosis by increasing Annexin V and TUNEL-positive cells. We also observed that selonsertib inhibited the ASK1/MAPK pathway, including p38 and c-Jun N-terminal kinase (JNK) in HSCs. Interestingly, dimethylnitrosamine (DMN)-induced liver fibrosis was significantly alleviated by selonsertib treatment in rats. Furthermore, selonsertib reduced collagen deposition and the expression of extracellular components such as α-smooth muscle actin (α-SMA), fibronectin, and collagen type I in vitro and in vivo. Taken together, selonsertib suppressed fibrotic response such as HSC proliferation and extracellular matrix components by blocking the ASK1/MAPK pathway. Therefore, we suggest that selonsertib may be an effective therapeutic drug for ameliorating liver fibrosis.

A Critical Evaluation and International Comparison of Pharmaceutical Consumption and Sales Statistics (국내 2018년 의약품 소비량 및 판매액 통계 산출 및 국제 비교)

  • Kim, Jihye;Lee, Dahee;Kim, Sooyon;Kim, Dong-Sook
    • Health Policy and Management
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    • v.30 no.3
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    • pp.311-325
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    • 2020
  • Background: Health statistics of pharmaceutical use and expenditure are essential to make and implement evidence-based pharmaceutical policy. This study aims to demonstrate the methods and results of pharmaceutical consumption and sales in 2018 according to the sources and methods given by the Organization for Economic Cooperation and Development (OECD). Methods: The medication list contains 39,346 medicines both reimbursed and non-reimbursed by the National Health Insurance in 2018. We used the therapeutic categories based on Anatomic Therapeutic Chemical Classification of World Health Organization. This study analyzed National Health Insurance claims data and supply data generated from wholesalers to health care facilities. The indicators are defined daily dose (DDD), per 1,000 inhabitants per day and US$ per capita. Results: In South Korea, the number of medications to which DDD were assigned was 18,055 and it was 45.9% of the total number of medications on the list. The consumption in anti-infective for systemic use (J) and musculo-skeletal system (M) was higher than the mean consumption among the OECD countries. The pharmaceutical sales per person in Korea was also higher than the mean sales per person across the OECD countries. Conclusion: We sought to explain the methods to produce pharmaceutical consumption and sales statistics which we had submitted annually to OECD. Considering the characteristics of pharmaceutical statistics, a direct comparison should be approached with caution. Since the growth in pharmaceutical spending has greatly increased over the past decade, we need to monitor pharmaceutical consumption and expenditure consistently.