• Title/Summary/Keyword: Targeted agents

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Evaluation of different molecular methods for detection of Senecavirus A and the result of the antigen surveillance in Korea during 2018

  • Heo, JinHwa;Lee, Min-Jung;Kim, HyunJoo;Lee, SuKyung;Choi, Jida;Kang, Hae-Eun;Nam, Hyang-Mi;Nah, JinJu
    • Korean Journal of Veterinary Service
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    • v.44 no.1
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    • pp.15-19
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    • 2021
  • Senecavirus A (SVA), previously known as Seneca Valley virus, can cause vesicular disease and neonatal losses in pigs that is clinically indistinguishable from foot-and-mouth disease virus (FMDV). After the first case report in Canada in 2007, it had been restrictively identified in North America including United States. But, since 2015, SVA emerged outside North America in Brazil, and also in several the Asian countries including China, Thailand, and Vietnam. Considering the SVA occurrence in neighboring countries, there has been a high risk that Korea can be introduced at any time. In particular, it is very important in terms of differential diagnosis in the suspected case of vesicular diseases in countries where FMD is occurring. So far, several different molecular detection methods for SVV have been published but not validated as the reference method, yet. In this study, seven different molecular methods for detecting SVA were evaluated. Among them, the method by Flowler et al, (2017) targeted to 3D gene region with the highest sensitivity and no cross reaction with other vesicular disease agents including FMDV, VSV and SVD, was selected and applied further to antigen surveillance of SVA. A total of 245 samples of 157 pigs from 61 farms submitted for animal disease diagnose nationwide during 2018 were tested all negative. In 2018, no sign of SVA occurrence have been confirmed in Korea, but the results of the surveillance for SVA needs to be continued and accumulated at a high risk of SVA in neighboring countries.

A systemic study on the vulnerability and fatality of prostate cancer patients towards COVID-19 through analysis of the TMPRSS2, CXCL10 and their co-expressed genes

  • Raza, Md. Thosif;Mizan, Shagufta
    • Genomics & Informatics
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    • v.20 no.3
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    • pp.31.1-31.15
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    • 2022
  • A pandemic of respiratory disease named coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is reported prostate cancer patients are susceptible to COVID-19 infection. To understand the possible causes of prostate cancer patients' increased vulnerability and mortality from COVID-19 infection, we focused on the two most important agents, transmembrane protease serine subtype 2 (TMPRSS2) and the C-X-C motif 10 (CXCL10). When SARS-CoV-2 binds to the host cell via S protein-angiotensin-converting enzyme-2 receptor interaction, TMPRSS2 contributes in the proteolytic cleavage of the S protein, allowing the viral and cellular membranes to fuse. CXCL10 is a cytokine found in elevated level in both COVID-19 and cancer-causing cytokine storm. We discovered that TMPRSS2 and CXCL10 are overexpressed in prostate cancer and COVID-19 using the UALCAN and GEPIA2 datasets. The functional importance of TMPRSS2 and CXCL10 in prostate cancer development was then determined by analyzing the frequency of genetic changes in their amino acid sequences using the cBioPortal online portal. Finally, we used the PANTHER database to examine the pathology of the targeted genes. We observed that TMPRSS2 and CXCL10, together with their often co-expressed genes, are important in the binding activity and immune responses in prostate cancer and COVID-19 infection, respectively. Finally, we found that TMPRSS2 and CXCL10 are two putative biomarkers responsible for the increased vulnerability and fatality of prostate cancer patients to COVID-19.

Selective cytotoxicity of a novel mitochondrial complex I inhibitor, YK-135, against EMT-subtype gastric cancer cell lines due to impaired glycolytic capacity

  • Yeojin, Sung;Seungbin, Cha;Sang Bum, Kim;Hakhyun, Kim;Seonghwi, Choi;Sejin, Oh;Minseo, Kim;Yunji, Lee;Gino, Kwon;Jooyoung, Lee;Joo-Youn, Lee;Gyoonhee, Han;Hyun Seok, Kim
    • BMB Reports
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    • v.55 no.12
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    • pp.645-650
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    • 2022
  • Epithelial-to-mesenchymal transition (EMT)-subtype gastric cancers have the worst prognosis due to their higher recurrence rate, higher probability of developing metastases and higher chemo-resistance compared to those of other molecular subtypes. Pharmacologically actionable somatic mutations are rarely found in EMT-subtype gastric cancers, limiting the utility of targeted therapies. Here, we conducted a high-throughput chemical screen using 37 gastric cancer cell lines and 48,467 synthetic small-molecule compounds. We identified YK-135, a small-molecule compound that showed higher cytotoxicity toward EMT-subtype gastric cancer cell lines than toward non-EMT-subtype gastric cancer cell lines. YK-135 exerts its cytotoxic effects by inhibiting mitochondrial complex I activity and inducing AMP-activated protein kinase (AMPK)-mediated apoptosis. We found that the lower glycolytic capacity of the EMT-subtype gastric cancer cells confers synthetic lethality to the inhibition of mitochondrial complex I, possibly by failing to maintain energy homeostasis. Other well-known mitochondrial complex I inhibitors (e.g., rotenone and phenformin) mimic the efficacy of YK-135, supporting our results. These findings highlight mitochondrial complex I inhibitors as promising therapeutic agents for EMT-subtype gastric cancers and YK-135 as a novel chemical scaffold for further drug development.

Decision and Practice of End-of-Life Care in Lung Disease Patients with Physicians Orders for Life Sustaining Treatment

  • Yu Mi Oh;Yoon Na Kang;Soo Jung Han;Jeong Hye Kim
    • Journal of Hospice and Palliative Care
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    • v.26 no.1
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    • pp.7-17
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    • 2023
  • Purpose: The purpose of this study was to analyze end-of-life care practices in lung disease patients with physician orders for life-sustaining treatment (POLSTs). Methods: We retrospectively analyzed data from medical records regarding the end-of-life care practices of POLST decisions for patients with lung disease hospitalized at a tertiary hospital in Seoul, South Korea. Data were collected from January 1 to June 30, 2021. Results: Of 300 total patients, 198 had lung cancer (66.0%) and 102 had non-malignant lung diseases (34.0%). A POLST was written for 187 patients (62.3%), and an advance directive was written for 20 patients (6.7%). Subsequent treatments were hemodialysis in 13 patients (4.3%), surgery in 3 patients (1.0%), and cardiopulmonary cerebral resuscitation in 1 patient (0.3%). Among cancer patients, chemotherapy was performed in 11 patients (3.7%), targeted therapy in 11 patients (3.7%), immunotherapy in 6 patients (2.0%), and radiation therapy in 13 patients (4.3%). Depending on the type of lung disease, types of treatment differed, including hemodialysis, ventilators, bilevel positive airway pressure, high-flow nasal cannulas, nebulizers, enteral nutrition, central line, inotropic agents, and opioids. Conclusion: Although the goals of hospice care are the same whether a patient has lung cancer or a non-malignant lung disease, because the characteristics of the respective diseases differ, end-of-life care practices and hospice approaches must be considered differently.

Comparison of vital sign stability and cost effectiveness between midazolam and dexmedetomidine during third molar extraction under intravenous sedation

  • Jun-Yeop, Kim;Su-Yun, Park;Yoon-Sic, Han;Ho, Lee
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.48 no.6
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    • pp.348-355
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    • 2022
  • Objectives: To compare the vital sign stability and cost of two commonly used sedatives, midazolam (MDZ) and dexmedetomidine (DEX). Patients and Methods: This retrospective study targeted patients who underwent mandibular third molar extractions under intravenous sedation using MDZ or DEX. The predictor variable was the type of sedative used. The primary outcome variables were vital signs (heart rate and blood pressure), vital sign outliers, and cost of the sedatives. A vital sign outlier was defined as a 30% or more change in vital signs during sedation; the fewer changes, the higher the vital sign stability. The secondary outcome variables included the observer's assessment of alertness/sedation scale, level of amnesia, patient satisfaction, and bispectral index score. Covariates were sex, age, body mass index, sleeping time, dental anxiety score, and Pederson scale. Descriptive statistics were computed including propensity score matching (PSM). The P-value was set at 0.05. Results: The study enrolled 185 patients, 103 in the MDZ group and 82 in the DEX group. Based on the data after PSM, the two samples had similar baseline covariates. The sedative effect of both agents was satisfactory. Heart rate outliers were more common with MDZ than with DEX (49.3% vs 22.7%, P=0.001). Heart rate was higher with MDZ (P=0.000). The cost was higher for DEX than for MDZ (29.27±0.00 USD vs 0.37±0.04 USD, P=0.000). Conclusion: DEX showed more vital sign stability, while MDZ was more economical. These results could be used as a reference to guide clinicians during sedative selection.

Access of Anti-cancer Treatment for Advanced Colon Cancer with Metastasis (전이를 동반한 진행성대장암의 항암 치료에 대한 접근)

  • Hyun Gun Kim
    • Journal of Digestive Cancer Research
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    • v.1 no.1
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    • pp.6-16
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    • 2013
  • Recent estimates for colon cancer incidence in Korea have been increased and continue to rank as the second most common in male and the third in female. Although colonoscopy has been known as the best screening tool for colon cancer, 20-25% of patients with colon cancer was diagnosed with stage IV cancer. During the past 10 years, intensive clinical studies helped to establish the value of palliative treatment for colon cancer with metastasis. The introduction of new chemotherapeutic agents such as irinotecan and oxaliplatin has led to a significant increase in tumor response and median survival. In advanced colon cancer, impressive prolongation or overall survival can be achieved through sequential application of combined systemic chemotherapy. In addition, targeted manipulation of molecular tumor mechanisms with new substances such as monoclonal antibodies against the epidermal growth factor receptor or vascular endothelial growth factor shows promising effects. Progress in the systemic treatment of colon cancer is evident, not only because of the significant increase in life expectancy in advanced colon cancer.

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Development and assessment of nano drug delivery systems for combined delivery of rosuvastatin and ezetimibe

  • Mohamed Ali Metwally;El-Yamani Ibrahim El-Zawahry;Maher Amer Ali;Diaa Farrag Ibrahim;Shereen Ahmed Sabry;Omnia Mohamed Sarhan
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.3
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    • pp.275-284
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    • 2024
  • Worldwide, cardiovascular disease is the main cause of death, which accordingly increased by hyperlipidemia. Hyperlipidemia therapy can include lifestyle changes and medications to control cholesterol levels. Statins are the medications of the first choice for dealing with lipid abnormalities. Rosuvastatin founds to control high lipid levels by hindering liver production of cholesterol and to achieve the targeted levels of low-density lipoprotein cholesterol, another lipid lowering agents named ezetimibe may be used as an added therapy. Both rosuvastatin and ezetimibe have low bioavailability which will stand as barrier to decrease cholesterol levels, because of such depictions, formulations of this combined therapy in nanotechnology will be of a great assistance. Our study demonstrated preparations of nanoparticles of this combined therapy, showing their physical characterizations, and examined their behavior in laboratory conditions and vivo habitation. The mean particle size was uniform, polydispersity index and zeta potential of formulations were found to be in the ranges of (0.181-0.72) and (-13.4 to -6.24), respectively. Acceptable limits of entrapment efficiency were affirmed with appearance of spherical and uniform nanoparticles. In vitro testing showed a sustained release of drug exceeded 90% over 24 h. In vivo study revealed an enhanced dissolution and bioavailability from loaded nanoparticles, which was evidenced by calculated pharmacokinetic parameters using triton for hyperlipidemia induction. Stability studies were performed and assured that the formulations are kept the same up to one month. Therefore, nano formulations is a suitable transporter for combined therapy of rosuvastatin and ezetimibe with improvement in their dissolution and bioavailability.

A study on the characteristics and pathogenicity of Aeromonas veronii isolated from infected goldfish (Carassius auratus) (피부 궤양이 발생한 금붕어(Carassius auratus)에서 분리한 Aeromonas veronii의 특성 및 병원성 분석)

  • Hyeon Ki Jung;Min Su Kim;Sok Ho Kim;Min Soon Choi
    • Journal of fish pathology
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    • v.37 no.1
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    • pp.79-88
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    • 2024
  • Aeromonas spp. infections have been reported to cause significant economic losses not only in the ornamental fish industry but also in aquaculture. In December 2022-January 2023, an Aeromonas infection occurred on a goldfish in korea, A gram-negative bacterium was isolated from the skin and internal organs of infected goldfish (Carassius auratus). The results showed that the isolate was identified as Aeromonas veronii using 16S rDNA targeted oilgpnucleotide primers, furthermore characteristics of A. veronii was confirmed by enterotoxin gene, infectious experiment, antibiotic resistance. In-vivo pathogenicity of isolates to goldfsh resulted in 100% mortality in challenged host within one week of post experiment injection. As a result of PCR analysis targeting three enterotoxin-encoding genes, cytotoxic enterotoxin (act) was identified in A. veronii isolate in this study. Antimicrobial susceptibility pattern of isolate showed it was to susceptible to most antimicrobial agents tested but resistant to ampicillin, imipenem, meropenem and clindamycin.

Evolution of Radiological Treatment Response Assessments for Cancer Immunotherapy: From iRECIST to Radiomics and Artificial Intelligence

  • Nari Kim;Eun Sung Lee;Sang Eun Won;Mihyun Yang;Amy Junghyun Lee;Youngbin Shin;Yousun Ko;Junhee Pyo;Hyo Jung Park;Kyung Won, Kim
    • Korean Journal of Radiology
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    • v.23 no.11
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    • pp.1089-1101
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    • 2022
  • Immunotherapy has revolutionized and opened a new paradigm for cancer treatment. In the era of immunotherapy and molecular targeted therapy, precision medicine has gained emphasis, and an early response assessment is a key element of this approach. Treatment response assessment for immunotherapy is challenging for radiologists because of the rapid development of immunotherapeutic agents, from immune checkpoint inhibitors to chimeric antigen receptor-T cells, with which many radiologists may not be familiar, and the atypical responses to therapy, such as pseudoprogression and hyperprogression. Therefore, new response assessment methods such as immune response assessment, functional/molecular imaging biomarkers, and artificial intelligence (including radiomics and machine learning approaches) have been developed and investigated. Radiologists should be aware of recent trends in immunotherapy development and new response assessment methods.

Structure of SARS-CoV-2 Spike Glycoprotein for Therapeutic and Preventive Target

  • Jaewoo Hong;Hyunjhung Jhun;Yeo-Ok Choi;Afeisha S. Taitt;Suyoung Bae;Youngmin Lee;Chang-seon Song;Su Cheong Yeom;Soohyun Kim
    • IMMUNE NETWORK
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    • v.21 no.1
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    • pp.8.1-8.17
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    • 2021
  • The global crisis caused by the coronavirus disease 2019 (COVID-19) led to the most significant economic loss and human deaths after World War II. The pathogen causing this disease is a novel virus called the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). As of December 2020, there have been 80.2 million confirmed patients, and the mortality rate is known as 2.16% globally. A strategy to protect a host from SARS-CoV-2 is by suppressing intracellular viral replication or preventing viral entry. We focused on the spike glycoprotein that is responsible for the entry of SARS-CoV-2 into the host cell. Recently, the US Food and Drug Administration/EU Medicines Agency authorized a vaccine and antibody to treat COVID-19 patients by emergency use approval in the absence of long-term clinical trials. Both commercial and academic efforts to develop preventive and therapeutic agents continue all over the world. In this review, we present a perspective on current reports about the spike glycoprotein of SARS-CoV-2 as a therapeutic target.