• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2113-2118
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• 2013

Aim and Background: Cervical cancer remains the third most common cancer in women globally after breast and colorectal cancer. Well-characterized biomarkers are necessary for early diagnosis and to predict metastatic progression and effective therapy. MiRNAs can regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or degradation in tumor cells. The present study was conducted to assess expression of miR93, miR200a, RECK, MMP2, MMP9 in invasive cervical carcinoma, and analyze their clinical significance. Method: A total of 116 patients with invasive cervical carcinoma and 100 patients undergoing hysterectomy for benign lesions were retrospectively examined. Quantitative real-time PCR was performed to determine expression of miR93 and miR200a while RECK, MMP2, MMP9 and MVD were assessed by immunohistochemical staining. Results: Cervical carcinoma patients demonstrated up-regulation of miR-93, miR-200a, MMP2 and MMP9, with down-regulation of RECK as compared to benign lesion tissues. RECK was significantly inversely related to invasion and lymphatic metastasis. The 5-year survival rate for patients with strong RECK expression was significantly higher than that with weakly expressing tumors. Conclusion: MiR-93 and miR-200a are associated with metastasis and invasion of cervical carcinoma. Thus together with RECK they are potential prognostic markers for cervical carcinoma. RECK cooperating with MMP2, MMP9 expression is a significant prognostic factor correlated with long-term survival for patients with invasive cervical carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1665-1667
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• 2013

Background: Ten to 30% of early breast cancer (EBC) patients develop brain metastasis (BM) during their follow-up. In this study, we aimed to evaluate importance of the lymph node ratio (LNR) in development of BM in EBC cases. Materials and Methods: Ninety patients whom had axillary metastases in lymph nodes at their initial diagnosis and developed BM during 5-year follow-up were detected in 950 EBC patients. LNR values were calculated for all patients and after categorization into 4 molecular sub-types as luminal A, luminal B HER-2 (+), HER-2 overexpressing and basal- like. Comparison was with control group patients who had similar characteristics. Results: In the comparison of all molecular sub-types of LNR, 54.9% and 28.4% values were found in patients with and without BM respectively (p<0.001). In the comparison of the LNR with control groups, a statistically significant differences were found with luminal A with BM (p=0.001), luminal B HER-2 (p=0.001), HER-2 overexpressing (p=0.027) and basal-like groups (p<0.001). In the evaluation of patients with BM, the highest ratio was found in the basal-like group (67.9%) and there was a statistically significant difference between this group and the others (p=0.048). Conclusions: EBC patients developing BM within 5 years follow-up had significantly higher LNRs for all molecular sub-types, especially in the basal-like group. Larger scale studies are now needed for evaluating LNR prognostic importance for EBC regarding BM development.

• Archives of Craniofacial Surgery
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• v.18 no.1
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• pp.37-43
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• 2017

Background: Skin cancer is the most common type of cancer. Of the 4 million skin lesions excised annually worldwide, approximately 2 million are considered cancerous. In this study, we aimed to describe a regional experience with skin cancers treated by a single senior surgeon and to provide a treatment algorithm. Methods: The medical records of 176 patients with head and neck non-melanocytic skin cancer (NMSC) who were treated by a single surgeon at our institution between January 2010 and May 2016 were retrospectively reviewed, and their data (age, sex, pathological type, tumor location/size, treatment modality) were analyzed. Patients with cutaneous squamous cell carcinoma (cSCC) who were classified as a high-risk group for nodal metastasis underwent sentinel node mapping according to the National Comprehensive Cancer Network guidelines. Results: Among the patients with NMSC who were treated during this period, basal cell carcinoma (BCC; n=102, 57.9%) was the most common pathological type, followed by cSCC (n=66, 37.5%). Most lesions were treated by complete excision, with tumor-free surgical margins determined via frozen section pathology. Thirty-one patients with high-metastasis-risk cSCC underwent sentinel node mapping, and 17 (54.8%) exhibited radiologically positive sentinel nodes. Although these nodes were pathologically negative for metastasis, 2 patients (6.5%) later developed lymph node metastases. Conclusion: In our experience, BCC treatment should comprise wide excision with tumor-free surgical margins and proper reconstruction. In contrast, patients with cSCC should undergo lymphoscintigraphy, as nodal metastases are a possibility. Proper diagnosis and treatment could reduce the undesirably high morbidity and mortality rates.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6575-6579
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• 2015

Background: Breast cancer (BC) is the most frequent malignancy among females and is a leading cause of death of middle-aged women. Herein, we evaluated baseline characteristics for BC patients and also compared these variables across ealry and late recurrence groups. Materials and Methods: Between 1995 to 2014, among female breast cancer patients referred to our oncology clinic, eighty-six were entered into our study. All had distant metastasis. Early recurrence was defined as initial recurrence within 5 years following curative surgery irrespective of site. Likewise, late recurrence was defined as initial recurrence after 5 years. No recurrence was defined for survivors to a complete minimum of 10 years follow-up. Significant prognostic factors associated with early or late recurrence were selected according to the Akaike Information Criterion. Results: The median follow-up was 9 years (range, 1-18 years). During follow-up period, 51 recurrences occurred (distant metastasis), 31 early and 20 late. According to the site of recurrence, there were 51 distant. In this follow-up period, 19 patients died. Compared with the early recurrence group, the no recurrence group had lower lymph node involvement and more p53 positive lesions but the late recurrence group had lower tumor size. In comparison to no recurrence, p53 (odds ratio [OR] 6.94, 95% CI 1.49-32.16) was a significant prognostic factor for early recurrence within 5 years. Conclusions: Tumor size, p53 and LN metastasis are the most important risk factors for distance recurrence especially in early recurrence and also between of them, p53 is significant prognostic factor for early recurrence.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1675-1679
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• 2014

Objectives: MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. Methods: Tissue samples were collected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN) dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic) cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96, miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR. Conclusions: Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8595-8601
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• 2014

Background: miR-200a expression is frequently altered in numerous cancers. The aim of the present study was to determine the role of microRNA-200a in advanced ovarian carcinomas. Materials and Methods: We measured miR-200a expression in 72 matched normal ovarian tissues and advanced ovarian carcinomas, and also two ovarian carcinoma cell lines (SKOV3 and SKOV3.ip1 - the latter being more invasive and metastatic than the parental SKOV3) by stem-loop real-time RT-PCR based on TaqMan microRNA assay using U6 as a reference. Levels of miR-200a expression were compared by disease stage, tumor grade, histology, and lymph node involvement. To evaluate the role of microRNA-200a, cell proliferation and invasion of SKOV-3 and SKOV-3.ip1 were analyzed with miR-200a inhibitor/mimic transfected cells. Results: Of 72 paired samples, 65 cancer tissues overexpressed microRNA-200a greater than two fold in comparison with matched normal epithelium. Specifically, patients with lymph node metastasis showed significant elevation. The level correlated with clinicopathological features, including high tumor grade, late disease stage, most notably with lymph node metastasis, but not with tumor histology. In addition, SKOV-3.ip1 cells also overexpressed miR-200a compared with SKOV-3, and miR-200a inhibitor transfected SKOV-3.ip1 cells showed significant reduction in cellular proliferation and invasion, while a miR-200a mimic stimulated the opposite behavior. Conclusions: We provide definitive evidence that miR-200a is up-regulated in a significant proportion of advanced ovarian carcinomas, and that elevated miR-200a expression facilitates tumor progression. Our findings support the notion that miR-200a is an onco-microRNA for ovarian cancer, and elevation is a useful potential diagnostic indicator. This study also provides a solid basis for further functional analysis of miR-200a in advanced ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5397-5402
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• 2013

The rates of morbidity and mortality of hepatocellular carcinoma (HCC) have not lessened because of difficulty in treating tumor metastasis. Mongolian Saussurea involucrata (SIE) possesses various anticancer activities, including apoptosis and cell cycle arrest. However, detailed effects and molecular mechanisms of SIE on metastasis are unclear. Thus, the present study was undertaken to investigate antimetastatic effects on HCC cells as well as possible mechanisms. Effects of SIE on the growth, adhesion, migration, aggregation and invasion of the SK-Hep1 human HCC cell line were investigated. SIE inhibited cell growth of metastatic cells in dose- and time-dependent manners. Incubation of SK-Hep1 cells with $200-400{\mu}g/mL$ of SIE significantly inhibited cell adhesion to gelatin-coated substrate. In the migration (wound healing) and aggregation assays, SIE treated cells showed lower levels than untreated cells. Invasion assays revealed that SIE treatment inhibited cell invasion capacity of HCC cells substantially. Quantitative real time PCR showed inhibitory effects of SIE on MMP-2/-9 and MT1-MMP mRNA levels, and stimulatory effects on TIMP-1, an inhibitor of MMPs. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by SIE, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 expression of SK-Hep1 cells. From these results, it was suggested that SIE could be used as potential anti-tumor agent.

• 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.