• The Korean Journal of Physiology and Pharmacology
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• 제27권6호
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• pp.521-531
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• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

• Journal of Microbiology and Biotechnology
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• 제33권9호
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• pp.1206-1212
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• 2023

The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N⁶-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2023년도 임시총회 및 춘계학술대회
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• pp.51-51
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• 2023

The world-wide rate of obesity is increasing continuously, representing a serious medical threat since it is associated with a variety of diseases including type 2 diabetes, cardiovascular disease, and numerous cancers. Sophora japonicais used as a traditional herb for medicinal purposes in eastern Asia. However, the anti-obesity effects of S. japonicafruit have not been explored. The aim of this study is to investigate the inhibition of adipocyte differentiation and adipogenesis by an ethanol extract of S. japonicafruit (EESF) in 3T3-L1 pre-adipocytes. Our results demonstrate that EESF suppressed the terminal differentiation of 3T3-L1 pre-adipocytes in a dose-dependent manner, as confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining. EESF significantly reduced the accumulation of cellular triglyceride, which was associated with a significant inhibition of the levels of pro-adipogenic transcription factors, including PPARγ, C/EBPα and C/EBPβ. In addition, EESF potentially down regulated the expression levels of adipocyte-specific proteins, including aP2 and leptin. In particular, EESF treatment effectively enhanced the activation of the AMPK signaling pathway; however, the co-treatment with compound C, an inhibitor of AMPK, significantly restored the EESF-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results indicate that EESF may exert an anti-obesity effect by controlling the AMPK signaling pathway, suggesting that the fruit extract of S. japonica may be a potential anti-obesity agent.

• 생명과학회지
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• 제33권11호
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• pp.876-886
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• 2023

두경부암(HNC)의 경우, 외과적 개입은 환자의 삶의 질에 심각한 영향을 미칠 수 있으며, 화학요법을 병행하게 된다. 그러나 화학요법에는 현저한 부작용이 있으므로 환자의 고통을 최소화하기 위한 보조 방법의 개발이 필요하다. 천궁(Ligusticum chuanxiong)은 동양 의학에서 뇌혈관 장애 및 두통에 사용되는 천연 허브이다. 본 연구에서는 네트워크 기반 약리학 및 분자 도킹 분석을 통해 천궁의 근본적인 항암기전을 예측하였다. 본 연구에서 HNC와 관련된 천궁의 공통 유전자를 밝혀내어 신경 활성 리간드의 대사 및 신경 전달 물질 경로와의 연관성을 확인했다. 본 연구는 천궁의 성분 중 하나인 (Z)-ligustilide 가 암세포 활성화에 관련된 heat shock protein 90의 ATP 결합 부위를 공유함을 입증했다. 이 결과는 천궁이 보조 항암제 개발을 위한 유망한 후보임을 시사하며, 향 후 더욱 새롭고 안전한 항암제의 연구개발에 과학적 근거를 제시하는 새로운 발견이다.

• 한국방사선학회논문지
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• 제17권7호
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• pp.1067-1073
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• 2023

유방암은 현대 여성들에게 가장 많이 발생하는 3대 암 중 하나로, 발생률이 급격하게 증가하고 있다. 가족력이 높고, 15% 정도의 사망률이 있어 고위험군에 속하므로 조기 검진 후 꾸준한 관리가 필요하다. 암을 진단할 수 있는 여러 장비 중 초음파는 위험성이 적고, 실시간으로 진단할 수 있다는 장점이 있다. 그러나 초음파 검사는 검사자의 기술에 따라 결과가 크게 달라진다. 이를 보완하기 위해 모션트래킹 기술을 접목하고자 한다. 모션트래킹은 삼차원의 공간에서 대상의 움직임에 따라 위치를 특정하고 분석하는 기술이다. 그렇기에 실시간 제어가 가능하고, 복잡하고 빠른 움직임도 실시간으로 기록할 수 있는 장점이 있다. 이러한 장점을 활용한 초음파 검사용 이미지 가이드 시스템 제작을 목표로 하였다. 이를 위해서 초음파스캐너의 위치를 3차원적으로 추정할 수 있는 자체 제작 완드(wand)를 설계하였고, 제작된 완드를 기반으로 초음파 영상의 위치를 추정하는 벡터 연산 알고리즘을 개발하였다. 이후, 연속 촬영을 통하여 3차원 공간에서 프로브의 위치와 초음파 영상의 위치를 나타내는 것까지 완료하였다. 이러한 실험은 Optitrack 사의 Primex 41 카메라를 초당 120 frame (Hz)으로 영상을 획득하며, 성공적으로 초음파 영상의 3차원 위치를 추정할 수 있었다. 이 실험 과정을 통해 초음파 검사와 모션트래킹의 접목으로 가이드 제작의 가능성을 확인하였다. 차후 추가적인 연구를 통해 초음파 검사 가이드를 제작하여 검사자의 기술과 상관없이 질 좋은 영상을 획득할 수 있기를 바란다.

• Journal of Gastric Cancer
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• 제23권4호
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• pp.574-583
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• 2023

Purpose: Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide. National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. Materials and Methods: We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the "before COVID" period, and the years 2020 and 2021 as the "during COVID" period. Results: Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it. Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. Conclusions: During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.

• Korean Journal of Radiology
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• 제22권3호
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• pp.464-475
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• 2021

Objective: This study aimed to evaluate the tumor doubling time of invasive lung adenocarcinoma according to the International Association of the Study for Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) histologic classification. Materials and Methods: Among the 2905 patients with surgically resected lung adenocarcinoma, we retrospectively included 172 patients (mean age, 65.6 ± 9.0 years) who had paired thin-section non-contrast chest computed tomography (CT) scans at least 84 days apart with the same CT parameters, along with 10 patients with squamous cell carcinoma (mean age, 70.9 ± 7.4 years) for comparison. Three-dimensional semiautomatic segmentation of nodules was performed to calculate the volume doubling time (VDT), mass doubling time (MDT), and specific growth rate (SGR) of volume and mass. Multivariate linear regression, one-way analysis of variance, and receiver operating characteristic curve analyses were performed. Results: The median VDT and MDT of lung cancers were as follows: acinar, 603.2 and 639.5 days; lepidic, 1140.6 and 970.1 days; solid/micropapillary, 232.7 and 221.8 days; papillary, 599.0 and 624.3 days; invasive mucinous, 440.7 and 438.2 days; and squamous cell carcinoma, 149.1 and 146.1 days, respectively. The adjusted SGR of volume and mass of the solid-/micropapillary-predominant subtypes were significantly shorter than those of the acinar-, lepidic-, and papillary-predominant subtypes. The histologic subtype was independently associated with tumor doubling time. A VDT of 465.2 days and an MDT of 437.5 days yielded areas under the curve of 0.791 and 0.795, respectively, for distinguishing solid-/micropapillary-predominant subtypes from other subtypes of lung adenocarcinoma. Conclusion: The tumor doubling time of invasive lung adenocarcinoma differed according to the IASCL/ATS/ERS histologic classification.

• 대한화학회지
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• 제68권3호
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• pp.151-159
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• 2024

Indian spices are well known for their numerous health benefits, flavour, taste, and colour. Recent Advancements in chemical technology have led to better extraction and identification of bioactive molecules (phytochemicals) from spices. The therapeutic effects of spices against diabetes, cardiac problems, and various cancers has been well established. The present in silico study aims to investigate the binding affinity of 29 phytochemicals from 11 Indian spices with two prominent proteins, BCL3 and CXCL10 involved in invasiveness and bone metastasis of breast cancer. The three-dimensional structures of 29 phytochemicals were extracted from PubChem database. Protein Data Bank was used to retrieve the 3D structures of BCL3 and CXCL10 proteins. The drug-likeness and other properties of compounds were analysed by ADME and Lipinski rule of five (RO5). All computational simulations were carried out using Autodock 4.0 on Windows platform. The proteins were set to be rigid and compounds were kept free to rotate. In-silico study demonstrated a strong complex formation (positive binding constants and negative binding energy ΔG) between all phytochemicals and target proteins. However, piperine and sesamolin demonstrated high binding constants with BCL3 (50.681 × 10³ mol^-1, 137.76 × 10³ mol^-1) and CXCL10 (98.71 × 10³ mol^-1, 861.7 × 10³ mol^-1), respectively. The potential of these two phytochemicals as a drug candidate was highlighted by their binding energy of -6.5 kcal mol^-1, -7.1 kcal mol^-1 with BCL3 and -6.9 kcal mol^-1, -8.2 kcal mol^-1 with CXCL10, respectively coupled with their favourable drug likeliness and pharmacokinetics properties. These findings underscore the potential of piperine and sesamolin as drug candidates for inhibiting invasiveness and regulating breast cancer metastasis. However, further validation through in vitro and in vivo studies is necessary to confirm the in silico results and evaluate their clinical potential.

• Journal of Chest Surgery
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• 제57권1호
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• pp.44-52
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• 2024

Background: Visceral pleural invasion (VPI) is a poor prognostic factor that contributes to the upstaging of early lung cancers. However, the preoperative assessment of VPI presents challenges. This study was conducted to examine intraoperative pleural carcinoembryonic antigen (pCEA) level and maximum standardized uptake value (SUVmax) as predictive markers of VPI in patients with clinical T1N0M0 lung adenocarcinoma. Methods: A retrospective review was conducted of the medical records of 613 patients who underwent intraoperative pCEA sampling and lung resection for non-small cell lung cancer. Of these, 390 individuals with clinical stage I adenocarcinoma and tumors ≤30 mm were included. Based on computed tomography findings, these patients were divided into pleural contact (n=186) and non-pleural contact (n=204) groups. A receiver operating characteristic (ROC) curve was constructed to analyze the association between pCEA and SUVmax in relation to VPI. Additionally, logistic regression analysis was performed to evaluate risk factors for VPI in each group. Results: ROC curve analysis revealed that pCEA level greater than 2.565 ng/mL (area under the curve [AUC]=0.751) and SUVmax above 4.25 (AUC=0.801) were highly predictive of VPI in patients exhibiting pleural contact. Based on multivariable analysis, pCEA (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.14-7.87; p=0.026) and SUVmax (OR, 5.25; 95% CI, 1.90-14.50; p=0.001) were significant risk factors for VPI in the pleural contact group. Conclusion: In patients with clinical stage I lung adenocarcinoma exhibiting pleural contact, pCEA and SUVmax are potential predictive indicators of VPI. These markers may be helpful in planning for lung cancer surgery.

• 대한영상의학회지
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• 제83권2호
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• pp.317-330
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• 2022

목적 본 연구는 신장종양 환자에서 시행한 고주파절제술 이후 신장 기능에 영향을 미치는 다양한 요소들에 대한 평가를 통해서 이들의 상관관계와 임상적 가치를 평가하기 위한 것이다. 대상과 방법 2010년 1월부터 2018년 12월까지 본원에서 ultrasonography, CT 유도하에 고주파절제술을 시행 받은 91명을 대상으로 선정하였다. 신기능을 평가하는 방법으로 시술 직전과 시술 이후 혈청 크레아티닌, 사구체 여과율을 측정하였다. 시술 전과 비교하여 혈청 크레아티닌 수치가 0.3 mg/dL 이상 증가하는 것을 유의미한 것으로 정하고, 이에 근거하여 두 그룹으로 분류하였다. 신장 기능 손상에 영향을 미치는 요소를 평가하기 위해서 다변수 로지스틱 회귀분석을 이용해서 그룹 간에 비교를 시행하였다. 결과 단일 신장, 3단계 이상의 만성 콩팥병, 요관 손상은 신장 기능 손상에서 통계적으로 유의한 의미가 있었다. 성별, 연령, 다른 암, 종양 크기, 위치, 성장 형태, 집합계와의 근접성 등은 통계적으로 유의하지 않았다. 신장 기능 수치의 시간에 따른 변화는 단일 신장, 3단계 이상의 만성 콩팥병, 요관 손상 유무에 따라서 통계적으로 유의하게 달랐다. 결론 고주파절제술 시행 전의 의학적 상태 중 단일 신장, 3단계 이상의 만성 콩팥병, 시술 이후 발생한 합병증 중 요관 손상은 시술 이후 발생하는 신장 기능 손상의 위험요소로 생각할 수 있다.