• BMB Reports
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• v.52 no.9
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• pp.548-553
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• 2019

Ets-1 is a prototype of the ETS protein family. Members of the ETS protein family contain a unique ETS domain. Ets-1 is associated with cancer progression and metastasis in many types of cancer. Many studies have shown a link between elevated expression of Ets-1 in cancer biopsies and poor survival. CCR7 is a chemokine that binds to specific ligand CCL21/CCL19. CCR7 expression is associated with tumor metastasis and infiltration into lymph nodes. The objective of this study was to test whether Ets-1 could regulate CCR7 expression and enhance tumor metastasis. Our data showed that CCR7 expression was downregulated in Ets-1-deficient T cells upon T-cell stimulation. Overexpression of Ets-1 increased CCR7 expression in breast cancer cell lines. In contrast, knockdown of Ets-1 reduced CCR7 expression. Ets-1 could directly bind to CCR7 promoter and mediate CCR7 expression in luciferase reporter assays and chromatin immunoprecipitation assays. Transactivation activity of Ets-1 was independent of the Pointed domain of Ets-1. Ets-1 could also enhance $NF-{\kappa}B$ and CBP transactivation of CCR7 promoter. Our results also showed that Ets-1 could modulate cancer cell transmigration by altering CCR7 expression in transwell assay and wound healing assay. Taken together, our data suggest that Ets-1 can enhance CCR7 expression and contribute to tumor cell migration.

• Journal of Gastric Cancer
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• v.21 no.4
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• pp.439-456
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• 2021

Purpose: Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism. Materials and Methods: The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry. Results: Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or HMGB1 overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression. Conclusions: Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.

• Journal of Society of Preventive Korean Medicine
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• v.26 no.3
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• pp.29-40
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• 2022

Objective : This study assessed the effect of a combination of Korean medicine on a thyroid papillary cancer patient who was diagnosed with local lymph node metastasis after thyroidectomy and lymph node dissection but did not want surgery. Methods : Gami-Palmultang administration and moxibustion(large Bmoxa cautery) were performed for six years. Treatment outcomes were evaluated with Brief Fatigue Inventory (BFI), Numerical Rating Scale (NRS), Insomnia Severity Index (ISI), Functional Assessment of Cancer Therapy-General (FACT-G), blood test/ CT imaging results, and patient's statements. Results : After the treatment, all symptoms have been alleviated, the quality of life has increased, and it has been maintained without further metastasis of tumors for six years. Conclusion : Korean medicine treatment along with active observation can be an alternative to patients who do not want surgical treatment after recurrence of local lymph nodes in thyroid papillary cancer, and can have positive results in improving the quality of life.

• Journal of Digestive Cancer Research
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• v.6 no.2
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• pp.73-77
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• 2018

A 70-year-old female diagnosed with pancreatic ductal adenocarcinoma was treated by pylorus-preserving pancreaticoduodenectomy (PPPD) and adjuvant concurrent chemoradiotherapy with 5-fluorouracil. Pancreatic ductal adenocarcinoma pT3N0 (stage IIA) was pathologically confirmed. Abdominal computed tomography (CT) findings 14 months after PPPD showed 10 mm sized solitary liver metastasis in segment 3. After 12 cycles of gemcitabine and 9 cycles of capecitabine plus oxaliplatin, the metastatic nodule increased in size to 27 mm. Tumorectomy at segment 3 of liver was done. 25 months after tumorectomy, chest CT showed 23 mm sized cavitary nodule in right upper lobe of lung. The result of percutaneous biopsy favored metastatic adenocarcinoma. Two sets of stereotactic body radiation therapy were done and the patient has survived without further disease progression for 6 years after initial diagnosis. This case suggests that selected population of recurrent pancreatic cancer patients with solitary liver or pulmonary metastasis can be treated by resection of metastatic site and ablative therapies.

• International Journal of Oncology
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• v.56 no.2
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• pp.630-640
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• 2020

Plant flavonoid 2',3,4',5,7-pentahydroxyflavone (morin hydrate), isolated from the family Moraceae (Morus alba L.), is known to have anti-inflammatory and anticancer effects. However, its pharmaceutical effects on metastasis have not been fully elucidated to date. Therefore, the current study investigated the effects of morin hydrate on cancer metastasis in MCF-7 human breast cancer cells. The results showed that morin hydrate suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration and invasion via the inhibition of matrix metalloproteinase (MMP)-9 activity. Furthermore, gene expression level of MMP-9, MMP-7, urokinase plasminogen activator (uPA), uPA receptor (uPAR) and fibronectin were significantly decreased by morin hydrate treatment. Morin hydrate inhibited the phosphorylation of Akt and glycogen synthase kinase (GSK)-3β, and downregulated the expression of an activator protein-1 subunit c-Fos. In addition, the GSK-3β phosphorylation and c-Fos expression were suppressed by PI3K/Akt pathway inhibitors, LY294002 and wortmannin. Taken together, these results demonstrated that morin hydrate reduced the metastatic potential in TPA-treated MCF-7 human breast cancer cells via the inhibition of MMPs, uPA and uPAR, and the underlying Akt/GSK-3β/c-Fos pathway. Therefore, the present investigation suggested that morin hydrate may be a natural substance with a preventive potential for metastasis in breast cancer cells.

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.24-30
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• 2009

Purpose: Today, Prostate cancer has been gradually increasing, according to the change of internal incidence rate of cancer. Generally, prostate cancer has lead to dead over 90%, in case of metastasis of lymph node and bone. So, innovative development of new radiopharmaceutical and imaging modality is progressed for detection of that metastasis, in nuclear medicine, now. Therefore, this study shows the usefulness of $^{18}F$-Fluoride PET/CT improved diagnosability on bone metastasis of prostate cancer. Materials and Methods: In this study, 33 male patients with prostate cancer were examined (The mean age: $67.8{\pm}10.2$ years old). Every patient was done each whole body bone scan (WBBS) and $^{18}F$-Fluoride positron emission tomography/computed tomography ($^{18}F$-Fluoride PET/CT). And then, using Receiver Operating Characteristic Curve (ROC curve), each sensitivity and specificity of two modalities was measured and compared with. Results: In 22 patients (66.6%) of all, bone metastasis was detected. And, in WBBS, sensitivity was 63.6%, specificity, 81.8%; in $^{18}F$-Fluoride PET/CT, sensitivity was 100% and specificity was 90.9%. As a result of ROC curve, AUROC (The Area under an ROC) of WBBS was 0.778, and that of $^{18}F$-Fluoride PET/CT, 0.942. Conclusions: $^{18}F$-Fluoride PET/CT was higher both sensitivity and specificity than WBBS, and it was valuable to detect bone metastasis of prostate cancer more definitely, with 3D imaging realization. Also, in $^{18}F$-Fluoride PET/CT, physiological images were acquired in more short time than WBBS, so, it was possible to reduce patient's waiting time and complaint. Therefore, it is considered that $^{18}F$-Fluoride PET/CT is able to improve diagnosability by offering more accurate images, as cuts in a share of high cost.

• The Korean Journal of Nuclear Medicine
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• v.35 no.5
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• pp.301-312
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• 2001

Purpose: Stomach cancer is one of the most common malignancies in Korea, but there is no report on FDG PET in patients with stomach cancer. We observed findings of FDG PET in patients with stomach cancer. Materials and Methods: In 13 patients with pre-operative stomach cancer, PET and CT were performed. Primary lesion and regional lymph nodes detection were aualyzed. Correlation between FDG uptake ratio and each prognostic factor of primary lesion was analyzed. In 19 patients diagnosed as recurrence or displaying suspicious symptoms, conventional work up including tumor marker and PET were performed. Recurrence detection of anastomotic site, distant metastasis, and tumor marker elevation were analyzed. Results: Sensitivity for primary lesion detection was 83.3% (CT 71.4%) and two submucosal lesions were undetected. FDG uptake ratio was variable and had no correlation with invasion-depth, size, Borrmann type, staging and differentiation. Sensitivity for regional lymph node detection was 58.3% (CT 58.3%) and the lesions less than 1cm were undetected. Sensitivity for recurrence detection was 100% but there were three false positives. Sensitivity for distant metastasis detection was 64.3% and significantly higher than that of conventional work-up (21.4%). Average of tumor marker level in patients who were confirmed as recurrence was higher than false positive. Conclusion: PET is more useful than conventional work up in distant metastasis detection when recurrence is suspected. In pre-operative stomach cancer, PET is comparable to CT for detection of primary lesion and regional lymph node metastasis and detection of distant metastasis requires further study.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.139-143
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• 2014

Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration. Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets ($81.7{\pm}0.45%$ vs $41.0{\pm}3.50%$, P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549, $4.33{\pm}0.33$ vs $0.33{\pm}0.33$, P=0.01; in SPC-A1, $2.67{\pm}0.33$ vs $0.00{\pm}0.00$, P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (> $200{\times}10^9/L$, 3 months versus ${\leq}200{\times}10^9/L$, 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7529-7536
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• 2013

Background and Aims: MicroRNA-21 (miR-21) is reported to be overexpressed and to contribute to proliferation, apoptosis and gemcitabine resistance in pancreatic ductal adenocarcinomas (PDACs). The aims of this study were to explore regulation of miR-21 expression by epigenetic change and its impact on chemoresistance and malignant properties of of pancreatic cancer. Materials and methods: We retrospectively collected 41 cases of advanced pancreatic cancer patients who were sensitive or resistant to gemcitabine and assessed levels of serum circulating miR-21 for correlation with cytotoxic activity. Histone acetylation in the miR-21 promoter was also studied in gemcitabine-sensitive and gemcitabine-resistant PDAC cells. Gemcitabine-resistant HPAC and PANC-1 cells were transfected with pre-miR-21 precursors (pre-miR-21) and antisense oligonucleotides (anti-miR-21), and were treated with TSA. Finally, invasion and metastasis assays were performed and alteration in mir-21, PTEN, AKT and pAKT level was evaluated in these cells. Results: Serum miR-21 levels were increased in gemcitabine-resistant PDAC patients compared with gemcitabine-sensitive subjects. The miR-21 levels were increased in 6 PDAC cells treated with gemcitabine significantly, associated with 50% inhibitory concentrations ($IC_{50}s$). Histone acetylation levels at miR-21 promoter were increased in PDAC cells after treatment with gemcitabine. Enhanced invasion and metastasis, increased miR-21 expression, decreased PTEN, elevated pAKT level were demonstrated in gemcitabine-resistant HPAC and PANC-1 cells. Pre-miR-21 transfection or TSA treatment further increased invasion and metastasis ability, decreased PTEN, and elevated pAKT levels in these two lines. In contrast, anti-miR-21 transfection could reverse invasion and metastasis, and PTEN and pAKT expressions induced by gemcitabine. Conclusions: MiR-21 upregulation induced by histone acetylation in the promoter zone is associated with chemoresistance to gemcitabine and enhanced malignant potential in pancreatic cancer cells.

• The Journal of Churna Manual Medicine for Spine and Nerves
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• v.10 no.1
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• pp.117-127
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• 2015

Objectives : Most of pains are important symptoms caused by cancer transpered to spine. Harpagophyti Radix Pharmacopuncture is highly effective in reducing fever, pain, inflammation but was never used to reduce pain from cancer transpered to spine. So I intended to use Harpagophyti Radix Pharmacopuncture to control pain. The purpose of this study is to evaluate the clinical application of Harpagophyti Radix Pharmacopuncture for Bone Metastasis of Breast Cancer and Spinal Stenosis. Methods : We examined patient with Bone Metastasis of Breast Cancer and Spinal Stenosis who admitted Jaseng Korean Medicine Hospital. The patient was treated by Korean Medicine treatment and Harpagophyti Radix Pharmacopuncture. This case was assessed by Numerical Rating Scale(NRS), Oswestry Low Back Pain Disability Index(ODI), Short-Form 36 Health Survey(SF-36), ROM(Range of Movement) and Special Test. Results : In this study, the patient's pain was controlled and NRS, ODI were decreased. I could identify the improvement in life quality from the positive change of SF-36 and also found out that treatment was successful from the improvement of ROM, Special test. Conclusions : Harpagophyti Radix Pharmacopuncture with Korean Medicine treatment for Bone Metastasis of Breast Cancer and Spinal Stenosis was proved to be useful to the pain relief and function recovery, but further research should take place for clear understanding of the exact amount of dosage and safety. Moreover it must be accompanied by long term follow up research.