• 대한두경부종양학회지
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• 제37권2호
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• pp.1-9
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• 2021

Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.

• Journal of Microbiology and Biotechnology
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• 제33권1호
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• pp.114-122
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• 2023

A family of signal transduction pathways known as wingless type (Wnt) signaling pathways is essential to developmental processes like cell division and proliferation. Mutation in Wnt signaling results in a variety of diseases, including cancers of the breast, colon, and skin, metabolic disease, and neurodegenerative disease; thus, the Wnt signaling pathways have been attractive targets for disease treatment. However, the complicatedness and large involveness of the pathway often hampers pinpointing the specific targets of the metabolic process. In our current study, we investigated the differential metabolic regulation by the overexpression of the Wnt signaling pathway in a timely-resolved manner by applying high-throughput and un-targeted metabolite profiling. We have detected and annotated 321 metabolite peaks from a total of 36 human embryonic kidney (HEK) 293 cells using GC-TOF MS and LC-Orbitrap MS. The un-targeted metabolomic analysis identified the radical reprogramming of a range of central carbon/nitrogen metabolism pathways, including glycolysis, TCA cycle, and glutaminolysis, and fatty acid pathways. The investigation, combined with targeted mRNA profiles, elucidated an explicit understanding of activated fatty acid metabolism (β-oxidation and biosynthesis). The findings proposed detailed mechanistic biochemical dynamics in response to Wnt-driven metabolic changes, which may help design precise therapeutic targets for Wnt-related diseases.

• Journal of Gastric Cancer
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• 제24권1호
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• pp.29-56
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• 2024

In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1285-1290
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• 2014

The aim was to determine whether ultrasound targeted microbubble destruction (UTMD) promotes dual targeting of HSP72 and HSC70 for therapy of castration-resistant prostate cancer (CRPC), to improve the specific and efficient delivery of siRNA, to induce tumor cell specific apoptosis, and to find new therapeutic targets specific of CRPC.VCaP cells were transfected with siRNA oligonucleotides. HSP70, HSP90 and cleaved caspase-3 expression were determined by real-time quantitative polymerase chain reaction and Western blotting. Apoptosis and transfection efficiency were assessed by flow cytometry. Cell viability assays were used to evaluate safety. We found HSP72, HSC70 and HSP90 expression to be absent or weak in normal prostate epithelial cells (RWPE-1), but uniformly strong in prostate cancerous cells (VCaP). UTMD combined with dual targeting of HSP72 and HSC70 siRNA improve the efficiency of transfection, cell uptake of siRNA, downregulation of HSP70 and HSP90 expression in VCaP cells at the mRNA and protein level, and induction of extensive tumor-specific apoptosis. Cell counting kit-8 assays showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting HSP70 therapy for PCa may be most efficacious, providng a novel, reliable, non-invasive, safe targeted approach to improve the specific and efficient delivery of siRNA, and achieve maximal effects.

• 항공우주정책ㆍ법학회지
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• 제28권2호
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• pp.37-61
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• 2013

국제법의 한 분야로서 국제 항공법상 무인항공기의 개념은 일련의 법률 체계내에서 규정되지 않고 있다. 무인항공기의 국제법상 규율은 국제 항공법상의 항공기, 특히 민간항공기와 국가항공기 개념의 유추 적용에 의존한다. 현재까지의 군용항공기와 민간항공기의 영공진입에 대한 국가의 태도와 학설상 인정된 국제관습법의 시각에서 무인항공기의 영공진입의 경우를 살펴볼 때, 무인항공기는 군용항공기로 국가들이 인식하고 있다고 추정된다. 무인항공기의 법적지위와 구분이 국제조약상 명확하지 않으나, 군용항공기의 관련 법규범이 무인항공기에 유추 적용된다고 판단된다. 다만, 무인항공기의 역사가 아직은 짧고, 축적된 사례가 충분하지는 않다는 점에서, 새로운 내용이 제기되고 법률적인 판단이 필요할 여지는 있다고 판단된다. 무인항공기는 새로운 무기 체계로서 정책 결정자들에게 새로운 수단과 가능성을 열어주었다. 특히 국가간의 전면적인 전쟁이 아닌, 새로운 형태의 전쟁이 진행되면서, 무인항공기는 다양한 정책적 선택의 폭을 넓혀주었다. 그중의 하나는 2차대전 이후에 정치적 정당성을 얻고 있는 이른바 정밀타격("surgical measure", 이를 언론에서는 "외과수술적 조치"라고 표현하기도 함)의 하나인 표적공격(targeted killing)의 수단으로서 무인항공기의 사용이다. 또한 9/11 테러라는 중대한 사건을 맞이하여 시작된 새로운 형태의 전쟁에서 무인항공기는 표적 공격만이 아닌 하나의 전쟁 수단으로서 등장하게 되었다. 무인항공기의 무력공격은 테러에 대한 무력 대응이 정치적 정당성을 얻으면서 시행되었고, 은밀하고 작은 규모의 표적 공격만이 아니라 하나의 전쟁 수단으로서 합법성이 주장되고 있다. 그리고 그 합법성의 논거는 테러에 대한 대응이 전쟁상태에 이른다는 전쟁상태론에서 찾아진다. 달리 말하면 전쟁상태론이 암살을 표적공격으로 합법화하고, 그 표적공격이 그래서 전쟁의 한 전략이고, 그 전략을 시행하는 수단이 무인항공기이다. 무인항공기 무력공격의 적법성에 관한 논의의 그러한 정치적 배경을 고려한다면, 무인항공기 무력공격을 둘러싼 국제 관습법의 형성은 아직 기대하기 어렵다고 판단된다. 무인항공기 PMF는 국제 조약 및 관습법상 아직까지 아무런 규율이 미치지 않는 영역이다. 다만 미국의 무인항공기 PMF 사례에 나타난 바와 같이, 미국의 국내법 및 무인항공기 PMF와의 계약의 영역에서 규율이 이루어진다고 판단된다.

• 한국식품과학회지
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• 제34권6호
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• pp.1134-1139
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• 2002

Campylobacter, Arcobacter, Helicobacter는 분류학적으로 동일한 rRNA superfamily Ⅵ로 식중독 이외에도 위궤양, 위암, 유산 및 신경 장애를 유발한다. Campylobacter, Arcobacter, Helicobacter를 오염된 식품 등에서 선택적으로 검출하기 위해 PCR, multiplex-PCR, RFLP(restriction fragment length polymorphism)의 기법을 이용하였다. Campylobacter, Arcobacter, Helicobacter의 16S rRNA를 target으로 하는 CHA primer를 사용하여 동일한 PCR product의 검출할 수 있었다. C. jejuni와 C.coli를 A. butzleri와 H. pylori로부터 선택적으로 검출하기 위해 fla A gene을 target으로 하는 pg3, p50을 사용하였으며, A. butzleri는 23S rRNA를 target으로 하는 Arco2, Butz를 이용했다. 또한 H. pyloyi는 isocitrate dehydrogenase gene을 target으로 하는 icd1, icd2를 사용하였고, C. jejuni는 ceuE gene을 target으로 하는 JEJ1, JEJ2를 이용하여 효과적으로 분리검출이 이루어졌다. 또한 제한효소 Dde I 을 사용하여 PCR-RFLP를 통해 C. jejuni, C. coli를 A. butzleri, H. pylori로부터 분리할 수가 있었다. 따라서 이러한 primer를 이용하여 C. jejuni, C. coli, A. butzleri, H. pylori가 함께 오염되었을 때 각각 균주의 선택적인 검출이 가능할 것이다.

• Investigative and Clinical Urology
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• 제59권6호
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• pp.363-370
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• 2018

Purpose: The aim of this study is to describe the technique and to report early results of transperineal magnetic resonance imaging and ultrasonography (MRI-US) fusion biopsy. Materials and Methods: A total of 75 patients underwent MRI-US fusion transperineal biopsy. Targeted biopsy via MRI-US fusion imaging was carried out for cancer-suspicious lesions with additional systematic biopsy. Detection rates for overall and clinically significant prostate cancer (csPCa) were evaluated and compared between systematic and targeted biopsy. In addition, further investigation into the detection rate according to prostate imaging reporting and data system (PI-RADS) score was done. Results of repeat biopsies were also evaluated. Results: Overall cancer detection rate was 61.3% (46 patients) and the detection rate for csPCa was 42.7% (32 patients). Overall detection rates for systematic and targeted biopsy were 41.3% and 57.3% (p<0.05), respectively. Detection rates for csPCa were 26.7% and 41.3%, respectively (p<0.05). The cancer detection rates via MRI fusion target biopsy were 30.8% in PI-RADS 3, 62.1% in PI-RADS 4 and 89.4% in PI-RADS 5. Rates of csPCa missed by targeted biopsy and systematic biopsy were 0.0% and 25.0%, respectively. The cancer detection rate in repeat biopsies was 61.1% (11 among 18 patients) in which 55.5% of cancer suspected lesions were located in the anterior portion. Conclusions: Transperineal MRI-US fusion biopsy is useful for improving overall cancer detection rate and especially detection of csPCa. Transperineal MRI-US targeted biopsy show potential benefits to improve cancer detection rate in patients with high PIRADS score, tumor located at the anterior portion and in repeat biopsies.

• 한국방사선학회논문지
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• 제16권7호
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• pp.1007-1014
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• 2022

표적 방사성핵종 치료(targeted radionuclide therapy, TRT)는 방사성의약품을 사용하여 종양세포를 치료하는 방법이다. 인체의 조직을 구성하는 세포와 핵은 구형과 타원형으로 구성되어 있지만, 암세포의 경우 다양한 형태의 세포 형태로 이루어져 있다. 이에 본 연구는 몬테카를로 방법을 통해 표적 방사성핵종 치료 시 사용되는 베타선 방출 핵종을 대상으로 단일 세포 내 세포핵의 크기 변화에 따른 세포 구성 영역별 흡수선량을 분석하였다. 세포는 5 ㎛, 10 ㎛ 두 가지의 크기의 구 형태로 선정하였으며, 세포의 내부 구성은 세포핵, 세포질, 세포 표면으로 구분하였으며, 세포핵의 크기 증가에 따른 흡수선량을 평가하였다. 그 결과, 표적 방사성핵종 중 ¹⁷⁷Lu이 세포 모든 구획에서 가장 높은 선량을 나타냈으며, 세포 내 핵의 비중이 증가함에 따라 세포 표면의 흡수선량은 증가되었으나, 세포질과 세포핵의 흡수선량은 감소하는 경향을 보였다. 따라서 표적 방사성핵종 치료 시 암세포의 크기를 고려한 방사성핵종의 선택과 적절한 방사능량 결정이 중요할 것으로 판단된다.

• Korean Journal of Radiology
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• 제21권4호
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• pp.471-482
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• 2020

Objective: We aimed to determine the optimized image-based surrogate endpoints (IBSEs) in targeted therapies for glioblastoma through a systematic review and meta-analysis of phase III randomized controlled trials (RCTs). Materials and Methods: A systematic search of OVID-MEDLINE and EMBASE for phase III RCTs on glioblastoma was performed in December 2017. Data on overall survival (OS) and IBSEs, including progression-free survival (PFS), 6-month PFS (6moPFS), 12-month PFS (12moPFS), median PFS, and objective response rate (ORR) were extracted. Weighted linear regression analysis for the hazard ratio for OS and the hazard ratios or odds ratios for IBSEs was performed. The associations between IBSEs and OS were evaluated. Subgroup analyses according to disease stage (newly diagnosed glioblastoma versus recurrent glioblastoma), types of test treatment, and types of response assessment criteria were performed. Results: Twenty-three phase III RCTs published between 2000 and 2017, including 8387 patients, met the inclusion criteria. OS showed strong correlations with PFS (standardized β coefficient [R] = 0.719), 6moPFS (R = 0.647), and 12moPFS (R = 0.638). OS showed no correlations with median PFS and ORR. In subgroup analysis according to types of therapies, PFS showed the highest correlations with OS in targeted therapies for cell cycle pathways (R = 0.913) and growth factor receptors and their downstream pathways (R = 0.962). 12moPFS showed the highest correlation with OS in antiangiogenic therapy (R = 0.821). The response assessment in neuro-oncology criteria provided higher correlation coefficients between OS and IBSEs than the Macdonald criteria. Conclusion: Overall, PFS is an optimized IBSE in targeted therapies for glioblastoma; however, 12moPFS is optimal in antiangiogenic therapy.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 1996년도 추계 학술대회 및 정기총회
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• pp.49-49
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• 1996