• Journal of Veterinary Science
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• v.25 no.1
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• pp.15.1-15.15
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• 2024

Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

• Clinical and Experimental Vaccine Research
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• v.11 no.3
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• pp.264-273
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• 2022

Purpose: Classical swine fever (CSF) reemerged on CSF-free Jeju Island where vaccination is not practiced by the unintentional injection of a live attenuated vaccine (modified live attenuated vaccines-low-virulence Miyagi [MLV-LOM]) in 2014. Since the Jeju provincial authority is considering adopting a voluntary immunization policy using a CSF-E2 subunit vaccine to combat LOM-derived CSF endemic, this study aimed to evaluate in Jeju herds. Materials and Methods: Two vaccination trials using the Bayovac CSF-E2 vaccine licensed for use in South Korea assessed the safety and humoral immunity of the CSF-E2 vaccine in breeding (trial 1) and nursery animals (trial 2) under farm application conditions. Results: Neither local nor systemic (including reproductive) adverse effects were objectively observed in pregnant sows and young piglets following a respective vaccination regime at pregnancy or weaning, respectively. Trial 1 showed that sows immunized with the CSF-E2 vaccine possessed high and consistent E2-specific and neutralizing antibody levels. The CSF-E2 vaccine-immunized pregnant sows subsequently conferred appropriate and steady passive immunity to their offspring. In trial 2, a double immunization scheme of the CSF-E2 vaccine in piglets at 40 and 60 days of age could elicit a consistent and long-lasting adequate antibody response. Additionally, the two trials detected no E^rns-specific antibody responses, indicating that CSF-E2 vaccine can differentiate infected from vaccinated animals (DIVA). Conclusion: Our trial data collectively provide invaluable information on applying the CSF-E2 subunit vaccine to circumvent the possible drawbacks associated with the MLV-LOM concerning the safety, efficacy, and DIVA, in the LOM-endemic field farms and contribute to advanced CSF eradication on Jeju Island.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.424-455
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• 2002

Diabetes mellitus is reaching epidemic proportions worldwide. The insufficiency of medication to cope with this burden has coincided with a dramatic rise in the prevalence of use of complementary and alternative therapies, especially herbal treatments. This surge in demand presents a challenge to prove the safety and efficacy of these treatments in diabetes. Korean red ginseng (steam treated Panax ginseng C.A. Meyer) is a strong candidate to succeed. It has been shown to possess a multitude of hypoglycemic effects and improve metabolic disturbances related to diabetes in in vitro and animal models. Data in humans is also emerging to support these benefits. Whether these results can be replicated in a rigorous clinical testing program is unclear. We therefore investigated the antidiabetic effects of Korean red ginseng in a series of 2 acute and 1 longterm randomized, double-blinded, placebo-controlled clinical trials. This paper provides the rationale for this program of study, expanding on the problem of diabetes, its management, and the possible role for Korean red ginseng. It then describes the design and expected findings.

• Journal of Korean Medical Science
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• v.33 no.44
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• pp.279.1-279.16
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• 2018

Magnetic resonance-guided focused ultrasound (MRgFUS) is a new emerging neurosurgical procedure applied in a wide range of clinical fields. It can generate high-intensity energy at the focal zone in deep body areas without requiring incision of soft tissues. Although the effectiveness of the focused ultrasound technique had not been recognized because of the skull being a main barrier in the transmission of acoustic energy, the development of hemispheric distribution of ultrasound transducer phased arrays has solved this issue and enabled the performance of true transcranial procedures. Advanced imaging technologies such as magnetic resonance thermometry could enhance the safety of MRgFUS. The current clinical applications of MRgFUS in neurosurgery involve stereotactic ablative treatments for patients with essential tremor, Parkinson's disease, obsessive-compulsive disorder, major depressive disorder, or neuropathic pain. Other potential treatment candidates being examined in ongoing clinical trials include brain tumors, Alzheimer's disease, and epilepsy, based on MRgFUS abilities of thermal ablation and opening the blood-brain barrier. With the development of ultrasound technology to overcome the limitations, MRgFUS is gradually expanding the therapeutic field for intractable neurological disorders and serving as a trail for a promising future in noninvasive and safe neurosurgical care.

• Translational and Clinical Pharmacology
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• v.26 no.4
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• pp.155-159
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• 2018

For regulatory approval of a new drug, the most preferred and reliable source of evidence would be randomized controlled trials (RCT). However, a great number of drugs, being developed as well as already marketed and being used, usually lack proper indications for children. It is imperative to develop properly evaluated drugs for children. And expanding the use of already approved drugs for other indications will benefit patients and the society. Nevertheless, to get an approval for expansion of indications, most often with off-label experiences, for drugs that have been approved or for the development of pediatric indications, either during or after completing the main drug development, conducting RCTs may not be the only, if not right, way to take. Extrapolation strategies and modelling & simulation for pediatric drug development are paving the road to the better approval scheme. Making the use of data sources other than RCT such as EHR and claims data in ways that improve the efficiency and validity of the results (e.g., randomized pragmatic trial and randomized registry trial) has been the topic of great interest all around the world. Regulatory authorities should adopt new methodologies for regulatory approval processes to adapt to the changes brought by increasing availability of big and real world data utilizing new tools of technological advancement.

• IMMUNE NETWORK
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• v.22 no.1
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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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• v.15 no.6
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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.

• Journal of Korean Physical Therapy Science
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• v.24 no.1
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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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• v.27 no.1
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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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• v.21 no.4
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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.