• Title/Summary/Keyword: Companion Diagnostics

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Application of Molecular Diagnostics Technology in the Development of a Companion Diagnostics for Malignant Solid Tumors (악성 고형암의 항암제 동반진단 기술에서 분자진단기술의 적용)

  • Kim, Jin-Hee
    • The Journal of the Korea Contents Association
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    • v.19 no.3
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    • pp.365-374
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    • 2019
  • Unlike benign tumors, malignant tumors are capable of metastasis, easy to relapse, poor survival, and low quality of life. In Korea, here is a tendency to treat the tumors collectively according to the General Principles of Cancer Chemotherapy(GPCC) of the Health Insurance Review & Assessment Service (HIRA). But recently, companion diagnostics(CDx) is recommended rather than unilateral medication because biomarker-based molecular diagnostics is possible to predict the drug response of patients before drug treatment. Not only domestic but also overseas Food and Drug Administratio (FDA) recommends the development of the CDx system at the stage of drug development to ensure the responsiveness and safety of medicines. In this study, I focused on the necessity of CDx development direction as well as CDx development status through literature review. Furthermore I also discussed CDx types according to the molecular diagnostic technology such as immunohistochemistry (IHC), polymerase chain reaction (PCR), in situ hybridization (ISH), and next-generation sequencing (NGS) not only in the approved CDx but also in the developing one by US FDA. And I suggested the technology issue of CDx development process such as a selection of molecular diagnostics at the time of release, a clear understanding of the CDx mechanism, and a convergence of drug with CDx development. The necessity of social insurance system also was proposed for CDx development.

Pros and cons of using aberrant glycosylation as companion biomarkers for therapeutics in cancer

  • Kang, Jeong-Gu;Ko, Jeong-Heon;Kim, Yong-Sam
    • BMB Reports
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    • v.44 no.12
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    • pp.765-771
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    • 2011
  • Cancer treatment has been stratified by companion biomarker tests that serve to provide information on the genetic status of cancer patients and to identify patients who can be expected to respond to a given treatment. This stratification guarantees better efficiency and safety during treatment. Cancer patients, however, marginally benefit from the current companion biomarker-aided treatment regimens, presumably because companion biomarker tests are dependent solely on the mutation status of several genes status quo. In the true sense of the term, "personalized medicine", cancer patients are deemed to be identified individually by their molecular signatures, which are not necessarily confined to genetic mutations. Glycosylation is tremendously dynamic and shows alterations in cancer. Evidence is accumulating that aberrant glycosylation contributes to the development and progression of cancer, holding the promise for use of glycosylation status as a companion biomarker in cancer treatment. There are, however, several challenges derived from the lack of a reliable detection system for aberrant glycosylation, and a limited library of aberrant glycosylation. The challenges should be addressed if glycosylation status is to be used as a companion biomarker in cancer treatment and contribute to the fulfillment of personalized medicine.

Objective Quantitation of EGFR Protein Levels using Quantitative Dot Blot Method for the Prognosis of Gastric Cancer Patients

  • Xin, Lei;Tang, Fangrong;Song, Bo;Yang, Maozhou;Zhang, Jiandi
    • 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.

A CHARACTERISTIC PLANETARY FEATURE IN CAUSTIC-CROSSING HIGH-MAGNIFICATION MICROLENSING EVENTS

  • Kim, Do-Eon;Han, Cheong-Ho
    • Journal of The Korean Astronomical Society
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    • v.42 no.3
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    • pp.33-37
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    • 2009
  • We propose a diagnostic that can resolve the planet/binary degeneracy of central perturbations in caustic-crossing high-magnification microlensing events. The diagnostic is based on the difference in the morphology of perturbation inside the central caustics induced by a planet and a wide-separation binary companion. We find that the contours of excess exhibit a concentric circular pattern around the caustic center for the binary-lensing case, while the contours are elongated or off-centered for the planetary case. This difference results in the distinctive features of the individual lens populations in the residual of the trough region between the two peaks of the caustic crossings, where the shape of the residual is symmetric for binary lensing while it tends to be asymmetric for planetary lensing. We determine the ranges of the planetary parameters for which the proposed diagnostic can be used. The diagnostic is complementary to previously proposed diagnostics in the sense that it is applicable to caustic-crossing events with small finite-source effect.

Cataclysmic Variables as Supernova Ia Progenitors

  • Kafka, Stella
    • Journal of Astronomy and Space Sciences
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    • v.29 no.2
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    • pp.163-167
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    • 2012
  • Although the identification of the progenitors of type Ia supernovae (SNeIa) remains controversial, it is generally accepted that they originate from binary star systems in which at least one component is a carbon-oxygen white dwarf (WD); those systems are grouped under the wide umbrella of cataclysmic variables. Current theories for SNeIa progenitors hold that, either via Roche lobe overflow of the companion or via a wind, the WD accumulates hydrogen or helium rich material which is then burned to C and O onto the WD's surface. However, the specifics of this scenario are far from being understood or defined, allowing for a wealth of theories fighting for attention and a dearth of observations to support them. I discuss the latest attempts to identify and study those controversial SNeIa progenitors. I also introduce the most promising progenitor in hand and I present observational diagnostics that can reveal more members of the category.

Investigation of the Molecular Diagnostic Market in Animals (동물 분자 진단 시장의 동향)

  • Park, Chang-Eun;Park, Sung-Ha
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.1
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    • pp.26-33
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    • 2019
  • Recently, the rapid growth of the companion animal market has led to the development of animal disease diagnosis kits. Therefore, the utility of the introduction of biomarkers for the development of animal molecular diagnostics is being reevaluated. A good biomarker should be precise and reliable, distinguish between normal and diseased states, and differentiate between different diseases. Recently reported genetic markers, tumor markers (cell free DNA, circulating tumor cells, granzyme, and skin tumors), and others (brucellosis, programmed death recovery-1, symmetric dimethylarginine, periostin, and cysteinyl leukotrien) have been developed. The biomarkers are used for risk prediction or for the screening, diagnosis, and monitoring of disease progression. The most important criteria for related biomarkers are disease specificity. Many potential biomarkers have emerged from laboratory and test studies, but they have not been validated in independent or large-scale clinical studies. Candidate biomarkers evaluate disease associations, verify the effectiveness of biomarkers for early detection and disease progression, and incorporate them into humans and animals. In the future, it will be necessary to reevaluate the utility of well-structured biomarker-based research and study the development of kits that can be used in on-site tests in accordance with the trends introduced in the diagnosis of animal diseases.

Evaluation of Clinical Efficacy and Safety Following Kyungokgo-Gamibang Administration in Dogs with Skin and Joint Diseases

  • Ga-Won Lee;Heyong-Seok Kim;Jong-Won Kim;Yang-Seon Moon;Chang-Su Na
    • Journal of Veterinary Clinics
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    • v.40 no.2
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    • pp.113-118
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    • 2023
  • Skin and joint diseases are relatively common in dogs. Nutritional complementation is one of the various management strategies for these disorders. This study evaluated the safety and clinical efficacy of Kyungokgo-gamibang in dogs with skin and joint diseases. Thirty dogs with diseases were included and divided into three groups: control group (n = 15), skin group (n = 10), and joint group (n = 5). The skin and joint groups were fed skin and joint gums composed of Kyungokgo-gamibang extract with standard treatment for four weeks. The control group included dogs with skin diseases who were administered standard skin infection treatment for 4 weeks. The physical and laboratory results showed no remarkable adverse effects of Kyungokgo-gamibang extract after its administration in dogs. Clinical efficacy was evaluated using quality of life scale, and levels of cytokines, including interferon-γ, interleukin (IL)-2, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1, and tumor necrosis factor-α, for 4 weeks in all groups. Dermatologic clinical scales were performed for 4 weeks in the control and skin groups. Both the control and skin groups had significantly decreased dermatologic clinical scales, including pruritus and erythema scales (p < 0.05). Among the cytokine levels, only IL-2 concentration was significantly decreased in the skin group after 4 weeks of administration of the Kyungokgo-gamibang extract (p = 0.032). There was no significant difference between the levels of cytokines on days 0 and 28 in the joint group. The quality of life scale was significantly increased after week 4 compared to week 0 in the skin (p = 0.008) and joint groups (p = 0.041). This study suggests that Kyungokgo-gamibang extract can be applied in managing dogs affected by skin and joint diseases without adverse effects.

Development of an Equine Antitoxin by Immunizing the Halla Horse with the Receptor-Binding Domain of Botulinum Neurotoxin Type A1

  • Kim, Na Young;Park, Kyung-eui;Lee, Yong Jin;Kim, Yeong Mun;Hong, Sung Hyun;Son, Won Rak;Hong, Sungyoul;Lee, Saehyung;Ahn, Hye Bin;Yang, Jaehyuk;Seo, Jong-pil;Lim, Yoon-Kyu;Yu, Chi Ho;Hur, Gyeung Haeng;Jeong, Seong Tae;Lee, Hun Seok;Song, Kyoung;Kang, Tae Jin;Shin, Young Kee;Choi, Joon-Seok;Choi, Jun Young
    • Journal of Microbiology and Biotechnology
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    • v.29 no.7
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    • pp.1165-1176
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    • 2019
  • Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, are the most toxic substances known. However, the number of currently approved medical countermeasures for these toxins is very limited. Therefore, studies on therapeutic antitoxins are essential to prepare for toxin-related emergencies. Currently, more than 10,000 Halla horses, a crossbreed between the native Jeju and Thoroughbred horses, are being raised in Jeju Island of Korea. They can be used for equine antitoxin experiments and production of hyperimmune serum against BoNT/A1. Instead of the inactivated BoNT/A1 toxoid, Halla horse was immunized with the receptor-binding domain present in the C-terminus of heavy chain of BoNT/A1 (BoNT/A1-HCR) expressed in Escherichia coli. The anti-BoNT/A1-HCR antibody titer increased rapidly by week 4, and this level was maintained for several weeks after boosting immunization. Notably, $20{\mu}l$ of the week-24 BoNT/A1-HCR(-immunized) equine serum showed an in vitro neutralizing activity of over 8 international units (IU) of a reference equine antitoxin. Furthermore, $20{\mu}l$ of equine serum and $100{\mu}g$ of purified equine $F(ab^{\prime})_2$ showed 100% neutralization of 10,000 $LD_{50}$ in vivo. The results of this study shall contribute towards optimizing antitoxin production for BoNT/A1, which is essential for emergency preparedness and response.