• 제목/요약/키워드: Companion Diagnostics

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

  • 김진희
    • 한국콘텐츠학회논문지
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    • 제19권3호
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    • pp.365-374
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    • 2019
  • 악성종양은 양성종양과 달리 전이가 가능하고 재발이 쉬울 뿐 아니라 생존율 및 삶의 질이 떨어지는 질환이다. 국내의 경우 악성종양 치료 시 건강보험심사평가원이 제시한 항암화학요법 일반원칙에 따라 일괄적으로 치료하는 경향이 있다. 하지만 근래에는 일방적인 약물치료보다는 동반진단제를 사용을 권고하는데 이는 바이오마커를 이용한 분자진단기법으로 동반진단하여 치료 전에 환자의 약물 반응을 예측할 수 있기 때문이며, 국내외 식품의약품안전처에서는 의약품의 반응성 및 안전성을 확보하기 위하여 신약개발단계에서 동반진단제를 함께 개발하기를 권고한다. 본 종설에서는 악성 고형암을 중심으로 동반진단제의 개발방향 및 개발현황을 문헌고찰을 통해 분석하였고, 동반진단제로 사용되는 다양한 분자진단기법, 예컨대 면역조직화학염색법, 중합효소연쇄반응법, 제자리부합법, 차세대염기서열분석법 등에 따른 동반진단제 개발현황 및 미국 식품의약품안전청의 승인사례를 조사하여 최신 동반진단 개발동향을 함께 살폈다. 그리고 동반진단제 개발과정에서 기술적 사항으로 허가시점에 맞춘 분자진단기술을 선택과 진단제에 대한 명확한 기전이해와 더불어 치료와 동반진단제의 융합을 제언하였고, 사회적으로 동반진단제에 대한 공공보험의 급여책정이 필요함을 제언하였다.

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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    • 제44권12호
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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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    • 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.

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

  • Kim, Do-Eon;Han, Cheong-Ho
    • 천문학회지
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    • 제42권3호
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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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    • 제29권2호
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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.

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

  • 박창은;박성하
    • 대한임상검사과학회지
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    • 제51권1호
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    • pp.26-33
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    • 2019
  • 최근 반려동물 시장의 급격한 성장으로 인해 동물용 질병 진단키트의 개발이 이루어지고 있다. 이에 동물 분자진단 개발을 위한 바이오마커의 도입으로 효용성을 재평가하고 있다. 좋은 바이오 마커는 정확하고 신뢰할 수 있어야 하고, 정상 상태와 질병 상태를 구별하고, 다른 질병을 구별해야 한다. 최근 보고된 유전마커나 세포유리 DNA, 순환종양세포, granzyme, 피부종양에 관한 종양마커의 개발이 활발히 이루어지고 있으며, 기타로는 브루셀라증, programmed death receptor-1, symmetric dimethylarginine, periostin, cysteinyl leukotrien이 활발히 도입되고 있다. 따라서 바이오마커는 위험 예측에 사용되거나 질병 진행의 스크리닝, 진단 및 모니터링에 사용된다. 관련 바이오 마커에 대한 가장 중요한 기준은 질병 특이성이며 많은 잠재적 바이오 마커가 실험실 및 시험 연구에서 출현했지만, 독립적인 실험이나 대규모 임상 연구에서 검증이 부족하다. 후보 바이오 마커는 질병과 연관성을 평가하고, 조기 발견, 질병 진행에 대한 바이오 마커의 유효성을 검증하여서 인간 및 동물에게 접목하게 된다. 향후 잘 구조화 된 바이오마커 기반 연구의 효용성을 재평가하고 동물 질병 진단에 도입되는 추세에 맞춰 현장검사에서 활용될 수 있는 키트의 개발에 대한 연구가 요구돼야 할 것으로 사료된다.

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
    • 한국임상수의학회지
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    • 제40권2호
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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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    • 제29권7호
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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.