• IMMUNE NETWORK
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• 제22권1호
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• pp.5.1-5.22
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• 2022

The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short halflife of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

• Asian-Australasian Journal of Animal Sciences
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• 제15권6호
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• pp.905-911
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• 2002

A study was carried out to assess the therapeutic effect of ascorbic acid in mastitis of dairy cows. The herd with a population of 250-275 lactating cows was screened for clinical and subclinical mastitis for a period of 5 months. Based on inclusion and exclusion criteria, eighteen animals each with clinical and subclinical mastitis in one quarter only were selected as study population. Twelve cows (group A) with normal udder and health were also selected as a healthy control. Clinical mastitis cows were grouped as B (n=12) and C (n=6). Cows of group B were treated with ascorbic acid at 25 mg/kg, subcutaneously for 5 consecutive days and intramammary infusion (Ampicillin sodium 75 mg and Cloxacillin sodium 200 mg/infusion) based on antibiotic sensitivity test, till complete recovery. Group C cows received only intramammary infusion till the complete recovery. Eighteen subclinical mastitis cows were divided in group D (n=12) and E (n=6). Cows of group D were treated with ascorbic acid at 25 mg/kg subcutaneously for 5 consecutive days while group E did not receive any treatment. California mastitis test (CMT), somatic cell count (SCC), physical changes of udder and milk were used to diagnose and classify the mastitis. Evaluation of the therapy was based on CMT score and physical changes of udder and milk. Sample size calculation was also performed but was not followed for control groups due to scarcity of cases. Adequate blinding was done when and where required to avoid the biases. Confounding variables like herd, age of the cow, stage of the lactation, season and geographical region were duly considered and adequate blocking was followed. Ascorbic acid was administered in clinical and subclinical cases even after cure considering its immunostimulatory and healing inducing effects. The recovery rate was faster in cases of clinical mastitis treated with ascorbic acid along with an intramammary infusion (group B) than the quarters of group C cows. Quarter wise the average duration/number (3.16${\pm}$0.11 days) of antimicrobial intramammary infusion was significantly (p<0.01) less in group B than that of average duration/number (5.33${\pm}$0.20 days) of group C. Subclinical mastitis cows treated with ascorbic acid showed 83.33% recovery while 16.77% did not respond to treatment till last day of study. Cows of group E (untreated) did not recovered from the mastitis. Subjective parameters viz. swelling, pain reflex of udder and physical changes in milk from quarter of ascorbic acid treated cows (group B) disappeared earlier than that of group C cows. It is concluded from this study that the ascorbic acid might be useful as an adjunct in case of clinical mastitis to get quick recovery with less number of intramammary infusions. High recovery rate in subclinical mastitis quarters of group D cows is appreciable and opens a new avenue to conduct further trials in a larger population in various field conditions. However, the pharmacology of ascorbic acid with particular reference to health of mammary gland needs to be investigated.

• 대한물리치료과학회지
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• 제24권1호
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• pp.59-68
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• 2017

Purpose : The aims of this study was to conduct a systematic literature review with meta-analysis to investigate the effect of virtual reality based rehabilitation program on balance of patient with stroke in Korean studies. Method : The studies for analysis were searched in electronic databases(Research Information Sharing Service; RISS, Korean Studies Information Service; KISS, DBpia, e-articles, National Assembly Library). The key words for search were 'virtual reality', 'stroke', and 'balance' and only randomized controlled trials and clinical controlled trials were included. Of 40 studies identified in the search, 20 studies met the criteria of this study and included in this meta-analysis. Result : The results were as follows: 1) The overall effect size of virtual reality based rehabilitation program was 0.557(95% critical interval; 0.340~0.774). 2) In the analysis of sub-categorical variables, effect size was as follows; the commercial game type(0.621) > virtual environment type(0.335); the dynamic balance measurement(0.750) > static balance measurement(0.226); randomized controlled trial(0.653) > clinical controlled trial(0.275); and thesis type(0.706) > article of journal type(0.339). 3) In the analysis of sub-continuous variables, as time of program(per session) increased, the balance increased(p<0.05). Conclusion : The results of this study showed that virtual reality based rehabilitation program moderately improves the balance of stroke patient. Further studies are recommended to investigate the effect of sub-variables related to virtual reality programs on motor functions of patient with stroke.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.25-33
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• 2019

Mesenchymal stem cells are classified as multipotent stem cells, due to their capability to transdifferentiate into various lineages that develop from mesoderm. Their popular appeal as cell-based therapy was initially based on the idea of their ability to restore tissue because of their differentiation potential in vitro; however, the lack of evidence of their differentiation to target cells in vivo led researchers to focus on their secreted trophic factors and their role as potential powerhouses on regulation of factors under different immunological environments and recover homeostasis. To date there are more than 800 clinical trials on humans related to MSCs as therapy, not to mention that in animals is actively being applied as therapeutic resource, though it has not been officially approved as one. But just as how results from clinical trials are important, so is to reveal the biological mechanisms involved on how these cells exert their healing properties to further enhance the application of MSCs on potential patients. In this review, we describe characteristics of MSCs, evaluate their benefits as tissue regenerative therapy and combination therapy, as well as their immunological properties, activation of MSCs that dictate their secreted factors, interactions with other immune cells, such as T cells and possible mechanisms and pathways involved in these interactions.

• Journal of Gastric Cancer
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• 제21권4호
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• pp.335-351
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• 2021

Purpose: An underlying factor for the failure of several clinical trials of anti-epidermal growth factor receptor (EGFR) therapies is the lack of an effective method to identify patients who overexpress EGFR protein. The quantitative dot blot method (QDB) was used to measure EGFR protein levels objectively, absolutely, and quantitatively. Its feasibility was evaluated for the prognosis of overall survival (OS) of patients with gastric cancer. Materials and Methods: Slices of 2×5 ㎛ from formalin-fixed paraffin-embedded gastric cancer specimens were used to extract total tissue lysates for QDB measurement. Absolutely quantitated EGFR protein levels were used for the Kaplan-Meier OS analysis. Results: EGFR protein levels ranged from 0 to 772.6 pmol/g (n=246) for all gastric cancer patients. A poor correlation was observed between quantitated EGFR levels and immunohistochemistry scores with ρ=0.024 and P=0.717 in Spearman's correlation analysis. EGFR was identified as an independent negative prognostic biomarker for gastric cancer patients only through absolute quantitation, with a hazard ratio of 1.92 (95% confidence interval, 1.05-3.53; P=0.034) in multivariate Cox regression OS analysis. A cutoff of 208 pmol/g was proposed to stratify patients with a 3-year survival probability of 44% for patients with EGFR levels above the cutoff versus 68% for those below the cutoff based on Kaplan-Meier OS analysis (log rank test, P=0.002). Conclusions: A QDB-based assay was developed for gastric cancer specimens to measure EGFR protein levels absolutely, quantitatively, and objectively. This assay should facilitate clinical trials aimed at evaluation of anti-EGFR therapies retrospectively and prospectively for gastric cancer.

• Journal of Gastric Cancer
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• 제23권1호
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• pp.224-249
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• 2023

Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

• 대한한의학회지
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• 제44권2호
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• pp.201-201
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• 2023

Objectives: Cupping therapy (CT) has been widely used in traditional medicine worldwide for various indications, including stroke. The aim of this study was to systematically review the clinical evidence of CT for stroke. Methods: To identify randomized controlled trials (RCTs) reporting the effectiveness and/or safety of CT, seven databases including PubMed, EMBASE, and Cochrane Library were searched for articles published from January 2000 to February 2021 without language restrictions. Meta-analysis was performed using Review Manager 5.4 software and the results were presented as mean difference (MD) or standard mean difference (SMD) for continuous variables and odds ratio (OR) for diverse variables with 95% confidence intervals (CIs). Assessment of the methodological quality of the eligible trials was conducted using the Cochrane Collaboration tool for risk of bias in RCTs. Results: Twenty-two RCTs with 1653 participants were included in the final analysis. CT provided additional benefit in improving upper limb motor function (Fugl-Meyer assessment for upper limb motor function, MD 6.91, 95% CI 4.64 to 1.67, P<0.00001) and spasticity (response rate, OR 3.28, 95% CI 1.31 to 8.22, P=0.08) in stroke survivors receiving conventional medical treatment. These findings were supported with a moderate level of evidence. CT did not significantly increase the occurrence of adverse events. Conclusions: This study demonstrated the potential of CT to be beneficial in managing a variety of complications in stroke survivors. However, to compensate for the shortcomings of the existing evidence, rigorously designed large-scale RCTs are warranted in the future.

• Korean Journal of Acupuncture
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• 제29권2호
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• pp.224-238
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• 2012

Objectives : From mechanism studies using animal models to high-level evidence based research such as randomized controlled trials or systematic reviews, various acupuncture studies have been performed. Nevertheless, the current research appears insufficient to satisfy clinicians' needs. We aimed at investigating clinicians' perception on the translational research and suggesting ways of symbiosis between basic research and clinical practice. Methods : Data were collected using a web-based questionnaire made available to Korean medicine doctors who were informed through social networking service or e-mail. The survey participants indicated their awareness of acupuncture research and their thoughts on the applicability of research in practice. Results : Forty-seven clinicians completed the survey. While most respondents agreed that acupuncture research is very important, only 40% of them answered that the results of acupuncture research are useful to their own practice. In more than half of those who responded to the survey, the current acupuncture research is not viewed as reflecting clinical practice very much. Respondents agreed that acupuncture research should be based on clinical practice, and they recognized the need to collect valid clinical data from real-world practice. Also, as many as 77% of clinicians had no scruple to participate in research programs. Conclusions : There is no doubt among practitioners that acupuncture research is necessary. More importantly, practice-based research remains essential in order to feed-back research outcomes to clinical practice. Communications and academic exchanges between clinicians and researchers can mutually benefit research and practice with better information, resulting in symbiosis.

• Biomolecules & Therapeutics
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• 제22권6호
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• pp.477-490
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• 2014

Non-thermal atmospheric-pressure plasma, also named cold plasma, is defined as a partly ionized gas. Therefore, it cannot be equated with plasma from blood; it is not biological in nature. Non-thermal atmospheric-pressure plasma is a new innovative approach in medicine not only for the treatment of wounds, but with a wide-range of other applications, as e.g. topical treatment of other skin diseases with microbial involvement or treatment of cancer diseases. This review emphasizes plasma effects on wound healing. Non-thermal atmospheric-pressure plasma can support wound healing by its antiseptic effects, by stimulation of proliferation and migration of wound relating skin cells, by activation or inhibition of integrin receptors on the cell surface or by its pro-angiogenic effect. We summarize the effects of plasma on eukaryotic cells, especially on keratinocytes in terms of viability, proliferation, DNA, adhesion molecules and angiogenesis together with the role of reactive oxygen species and other components of plasma. The outcome of first clinical trials regarding wound healing is pointed out.

• Journal of Periodontal and Implant Science
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• 제29권3호
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• pp.539-553
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• 1999

The purpose of this 6-months study was to compare the clinical and radiographic outcomes following guided tissue regeneration treating human mandibular Class II furcation defects with a bioabsorbable BioMesh barrier(test treatment) or a nonabsorbable ePTFE barrier(control treatment). Fourteen defects in 14 patients(mean age 44 years) were treated with BioMesh barriers and ten defects in 10 patients(mean age 48 years) with ePTFE barriers. After initial therapy, a GTR procedure was done. Following flap elevation, root planing, and removal of granulation tissue, each device was adjusted to cover the furcation defect. The flaps were repositioned and sutured to complete coverage of the barriers. A second surgical procedure was performed at control sites after 4 to 6 weeks to remove the nonresorbable barrier. Radiographic and clinical examinations(plaque index, gingival index, tooth mobility, gingival margin position, pocket depth, clinical attachment level) were carried out under standardized conditions immediately before and 6 months after surgery. Furthermore, digital subtraction radiography was carried out. All areas healed uneventfully. Surgical treatment resulted in clinically and statistically equivalent changes when comparisons were made between test and control treatments. Changes in plaque index were 0.7 for test and 0.4 for control treatments; changes in gingival index were 0.9 and 0.5. In both group gingival margin position and pocket depth reduction was 1.0mm and 3.0mm; clinical attachment level gain was 1.9mm. There were no changes in tooth mobility and the bone in radiographic evaluation. No significant(p${\leq }$0.05) difference between the two membranes could be detected with regard to plaque index, gingival index, gingival margin position, pocket depth, and clinical attachment level. In conclusion, a bioabsorbable BioMesh membrane is effective in human mandibular Class II furcation defects and a longer period study is needed to fully evaluate the outcomes.