• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 1993년도 제27차 학술대회 초록집
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• pp.84-84
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• 1993

17번 염색체의 단완에 위치하여 종양의 억제에 관여하는 p53유전자의 돌연변이로 인한 불활성 p53단백의 과도발현이 유방암과 대장암을 비롯한 인체의 여러 암에 있어서 보고되었으며 일부 암에서는 예후인자로서의 가능성이 제시되었다. 저자들은 비교적 완만히 성장하지만 국소재발 및 원격전이가 잦은 두경부 영역의 선양낭포암에 있어서 p53 단백 발현 양상 및 예후 인자로의 가능성을 알아보고자 1982년부터 1991년 사이에 서울대학병원에서 병리조직학적으로 진단받은 환자 중 추적관찰이 가능하였고 병리조직을 얻을 수 있었던 23례에 대해 p53 단백에 대한 단클론항체를 이용하여 면역 조직화학적 염색을 시행하여 다음과 같은 결과를 얻었다. 총 23례 중 p53단백의 양성 발현을 보인 경우는 7fP(34%)이었으며, p53단백의 양성 발현과 국소재발 또는 원격전이와의 사이에 유의한 상관관계는 없었다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권6호
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• pp.2805-2810
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• 2016

Background: Differentiated thyroid cancer is the most common endocrine malignancy with a generally good prognosis. Knowing long-term outcomes of each patient helps management planning. The study was conducted to develop and validate a clinical prognostic score for predicting disease remission in patients with differentiated thyroid cancer based on patient, tumor and treatment factors. Materials and Methods: A retrospective cohort study of 1,217 differentiated thyroid cancer patients from two tertiary-care hospitals in the Northeast of Thailand was performed. Associations between potential clinical prognostic factors and remission were tested by Cox proportional-hazards analysis in 852 patients (development cohort). The prediction score was created by summation of score points weighted from regression coefficients of independent prognostic factors. Risks of disease remission were estimated and the derived score was then validated in the remaining 365 patients (validation cohort). Results: During the median follow-up time of 58 months, 648 (76.1%) patients in the development cohort had disease remission. Five independent prognostic factors were identified with corresponding score points: duration from thyroid surgery to $^{131}I$ treatment (0.721), distant metastasis at initial diagnosis (0.801), postoperative serum thyroglobulin level (0.535), anti-thyroglobulin antibodies positivity (0.546), and adequacy of serum TSH suppression (0.293). The total risk score for each patient was calculated and three categories of remission probability were proposed: ${\leq}1.628$ points (low risk, 83% remission), 1.629-1.816 points (intermediate risk, 87% remission), and ${\geq}1.817$ points (high risk, 93% remission). The concordance (C-index) was 0.761 (95% CI 0.754-0.767). Conclusions: The clinical prognostic scoring model developed to quantify the probability of disease remission can serve as a useful tool in personalized decision making regarding treatment in differentiated thyroid cancer patients.

• BMB Reports
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• 제52권7호
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• pp.457-462
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• 2019

[18F]Fluorodeoxyglucose (FDG) PET/CT imaging has been widely used in the diagnosis of malignant tumors. ATPase family AAA domain-containing protein 2 (ATAD2) plays important roles in tumor growth, invasion and metastasis. However, the relationship between [18F]FDG accumulation and ATAD2 expression remains largely unknown. This study aimed to investigate the correlation between ATAD2 expression and [18F]FDG uptake in lung adenocarcinoma (LUAD), and elucidate its underlying molecular mechanisms. The results showed that ATAD2 expression was positively correlated with maximum standardized uptake value ($SUV_{max}$), total lesion glycolysis (TLG), glucose transporter type 1 (GLUT1) expression and hexokinase2 (HK2) expression in LUAD tissues. In addition, ATAD2 knockdown significantly inhibited the proliferation, tumorigenicity, migration, [18F]FDG uptake and lactate production of LUAD cells, while, ATAD2 overexpression exhibited the opposite effects. Furthermore, ATAD2 modulated the glycometabolism of LUAD via AKT-GLUT1/HK2 pathway, as assessed using LY294002 (an inhibitor of PI3K/AKT pathway). In summary, to explore the correlation between ATAD2 expression and glycometabolism is expected to bring good news for anti-energy metabolism therapy of cancers.

• 생명과학회지
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• 제20권4호
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• pp.528-534
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• 2010

본 연구에서는 흑마늘 열수 추출물(ABG)의 암세포 전이억제 효능을 검정하였다. AGS AGS 인체위암세포의 이동성과 침윤성을 억제하였으며, 이는 TER의 증가와 연관성이 있었다. 또한 ABG에 의한 AGS 위암세포의 침윤성 억제는 TIMPs 발현 증가에 의한 MMPs의 발현 및 활성 저하에 의한 것임을 알 수 있었다. 아울러 AGS 위암세포에서 과발현을 나타내는 TJ 단백질인 claudins의 발현 저하 등이 ABG의 항전이 효과에 연관되어 있음을 알 수 있었다. 이상의 결과는 흑마늘 열수 추출물이 단순한 암세포의 증식억제를 통한 암예방 및 항암활성 뿐만 아니라 암세포의 전이 또한 효과적으로 억제할 수 있음을 보여주며, 이와 연관된 보다 구체적인 분자세포생물학적 접근 및 in vivo 연구의 필요성이 요구됨을 의미한다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1457-1461
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• 2012

Purpose: Non small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting EGFR mutations have been developed, most advanced cases are still incurable. New targets for anticancer drugs are demanded. The kringle 1 domain of hepatocellular growth factor alpha chain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor in hepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not been reported to date. Method: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advanced NSCLC to investigate the impact of HGFK1 on survival. Results: Results revealed 33 (30.1%) patients were classified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but not with lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expression and tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that both overall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer than those of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinib inhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431 and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreased phosphorylation of ERK and STAT5. Conclusions: HGFK1 may be a useful prognostic factor of advanced NSCLC patients and a potential drug for gefitinib resistant patients.

• Journal of Korean Neurosurgical Society
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• 제64권6호
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• pp.983-994
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• 2021

Objective : The effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC). Methods : We analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1-3 and 3-5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated. Results : After GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0-17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150-0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5-11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment. Conclusion : The small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.

• Advances in nano research
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• 제12권6호
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• pp.639-652
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• 2022

The prolyl 3-hydroxylase family member 4 (P3H4), is associated with post-translational modification of fibrillar collagens and aberrantly activated in cancer leading to tumor progression. However, its role in clear cell renal cell carcinoma (ccRCC) is still unknown. Here we reported that P3H4 was highly expressed in renal cancer tissues and significantly positive correlated with poor prognosis. Knockdown of P3H4 inhibited the proliferation, migration and metastasis of renal cancer cells in vitro and in vivo, and also, overexpression of it enhanced the oncogenic process. Mechanistically, P3H4 depletion decreased the levels of GDF15-MMP9 axis and repressed its downstream signaling. Further functional studies revealed that inhibition of GDF15 suppressed renal cancer cell growth and GDF15 recombinant human protein (rhGDF15) supplementation effectively rescued the inhibitory effect induced by P3H4 knockdown. Moreover, decreased levels of MMP9 caused by inhibition of P3H4-GDF15 signaling constrained the expression of PD-L1 and suppression of P3H4 accordingly promoted anti-tumor immunity via stimulating the infiltration of CD4+ and CD8+ T cells in syngeneic mice model. Taken together, our findings firstly demonstrated that P3H4 promotes ccRCC progression by activating GDF15-MMP9-PD-L1 axis and targeting P3H4-GDF15-MMP9 signaling pathway can be a novel strategy of controlling ccRCC malignancy.

• ALGAE
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• 제29권4호
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• pp.355-366
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• 2014

Fucoxanthin is known to be an effective cell proliferation inhibitor with anti-tumor and anti-angiogenic activities. However, there is a lack of data regarding the biological effects of cis isomers of fucoxanthin. To assess the potential therapeutic properties of 9'-cis-(6'R) fucoxanthin (FcA), and 13-cis and 13'-cis-(6'R) fucoxanthin complex (FcB) isolated from Sarggassum siliquastrum, we investigated their inhibitory effects on matrix metalloproteinases (MMPs) in phorbol 12-myristate 13-acetate (PMA)-induced human fibrosarcoma (HT1080) cells. FcA and FcB reduced MMP-2 and MMP-9 protein and mRNA levels, as well as the migration of these cells, in a dose-dependent manner. Additionally, FcA and FcB increased levels of MMPs inhibition factors such as tissue inhibitor of metalloproteinase-1. FcA and FcB significantly inhibited the transcriptional activity of nuclear factor ${\kappa}B$ (NF-${\kappa}B$) and by inhibiting c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases. Our results demonstrate that suppression of the NF-${\kappa}B$, JNK, and p38 signaling pathways may inhibit PMA-induced MMP-2 and MMP-9 activity. Therefore, FcA and FcB may be useful in noninvasive therapeutic strategies against fibrosarcoma metastasis.

• Journal of Applied Biological Chemistry
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• 제58권3호
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• pp.219-226
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• 2015

본 연구에서는 레몬 잎 메탄올 추출물(MLL)의 인간 유방암 줄기 세포인 MCF-7-SC에 대한 항암 활성을 조사하였다. MLL이 MCF-7-SC에서 apoptosis를 유도하였으며, 이를 apoptotic body의 형성, sub-G1 phase 및 annexin V-positive 세포와 Bax/Bcl-2 ratio의 증가, caspase-9과 caspase-3의 활성화 및 PARP의 절 단을 통하여 확인하였다. 동시에 MCF-7-SC에서 MLL은 acidic vesicular organelles의 형성, LC3-II의 축적 증가, Akt/mTOR/p70S6K의 활성 억제 등을 통하여 autophagy를 유도하였다. Epithelial-mesenchymal transition (EMT)는 세포가 전이 상태를 획득하기 위한 중요한 과정이며, 이 기작은 암세포가 전이되는 것을 억제함에 있어서 중요한 표적이 된다. 낮은 농도에서의 MLL은 epithelial 마커 단백질인 E-cadherin이 증가와 mesenchymal 마커 단백질인 Snail과 Slug의 발현 감소를 통해 EMT 과정을 저해함으로써 MCF-7-SC에서 항전이 활성을 나타내었다. 본 연구에서는 레몬 잎 메탄올 추출물이 농도 의존적으로 유방암 줄기세포에 대해 세포 독성과 항전이 활성을 나타내고 있으며, 따라서 레몬잎은 항암 소재로서의 개발 가능성이 높은 식물이라고 사료된다.

• 생명과학회지
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• 제24권1호
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• pp.8-13
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• 2014

여성에게 특히 높은 발병률을 보이는 유방암은 다양한 인자에 의해 암세포 침투와 전이가 발생한다. 그중에서 MMP-9은 유방암에서 높은 발현율을 나타내며, 유방암 세포의 침투와 전이에 주요하게 작용한다. MMP-9은 다양한 성장인자와 사이토카인, PMA 등에 의해 발현이 유도되며 세포 내 자연적으로 발생된 내생적 억제인자인 TIMP-1과 -2에 의해 그 활성 및 발현이 조절된다. MMP-9의 활성 및 발현을 저해하기 위해 사용한 물질은 모링가 추출물로 모링가의 모든 부위가 다양한 질환을 치료하는 것으로 알려져 있다. 이 연구에서는 대표적으로 모링가씨, 뿌리, 잎, 열매 추출물질을 이용하여 MMP-9의 활성억제 유무를 연구하였으며, MCF-7 세포에서 모링가 뿌리추출물이 MMP-9을 가장 효과적으로 억제하였다. 또한 MDA-MB-231을 이용한 비교실험에서도 세포특이성 없이 MMP-9의 활성 및 발현이 모링가 뿌리 추출물에 의해 억제되었고 단백질과 mRNA 발현에서도 동일한 결과가 도출되었다. 뿐만 아니라 암세포 침투실험에서도 모링가 뿌리 추출물에 의해 암세포 침투가 50% 이상 감소 되었으나, TIMP-1과 -2 mRNA 발현은 모링가 뿌리 추출물에 의해 저해되지 않았으므로 모링가 뿌리 추출물이 MMP-9 활성 및 발현 저해를 통해 암세포 침투를 저해시키는 것으로 예상된다. 그리고 MMP-9 활성 및 발현 조절기전을 확인하기 위해 MAP kinase의 인산화를 확인한 실험에서 모링가 뿌리 추출물이 ERK와 JNK의 인산화를 억제시킴을 확인하였다. 결론적으로 이 실험을 통해 모링가 추출물 중 뿌리 추출물이 MMP-9 활성 및 발현저해에 가장 효과적이며, ERK와 JNK의 인산화 조절을 통해 MMP-9의 활성 및 발현을 직접적으로 조절함을 확인할 수 있었다.