• Korean Journal of Head & Neck Oncology
• /
• v.21 no.1
• /
• pp.15-20
• /
• 2005

Objectives: The hepatocyte growth factor(HGF)/c-Met pathway may play various roles in the carcinogenesis of various organs. Although HGF/c-Met signalling pathway has been shown to demonstrate various cellular responses including mitogenic, proliferative, morphogenic and angiogenic activities, the study on their expression related to clinicopathological parameters in thyroid tumor is relatively rare. So we want to find out the clinical significance of the c-Met in thyroid tumor. Materials and Methods: We assess the mRNA and protein expression of the c-Met genes by means of RT-PCR method and the immunohistochemical stain in 100 cases of thyroid tumors(50 papillary carcinomas, 10 follicular carcinomas, 20 follicular adenomas, 20 nodular hyperplasia). Results: By RT-PCR, c-Met mRNA was detected in 43(86%) in papillary carcinoma, 4(40%) in follicular carcinoma, 4(20%) in follicular adenoma and 2(10%) in nodular hyperplasia cases. By immunohistochemistry, c-Met protein expression was detected in 44(88%), 2(20%), 3(15%) and 1(5%). Expression of the c-Met mRNA and protein expression was significantly highly recognized in papillary carcinoma. The c-Met protein overexpression was significantly correlated with the grade of the differentiation. Conclusion: These results suggest that c-Met expression may be associated with thyroid papillary cancer progression. The differential expression of c-Met protein and mRNA suggests that these molecules may be a reliable diagnostic marker in thyroid papillary cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.6
• /
• pp.2781-2785
• /
• 2016

Background: Matric metalloproteinase (MMP) 13 gene expression is increased in esophageal squamous cell carcinomas (ESCCs) and associated with increasing tumor invasion, lymph node involvement and decreased survival rates. Levels of the circulating enzyme may be elevated and used as a marker of tumor progression. In this study, clinical application of MMP-13 serum levels was evaluated for early detection, prediction of prognosis and survival time of ESCC patients. Materials and Methods: Serum levels of MMP13 were determined by ELISA in 66 ESCC patients prior of any treatment and 54 healthy controls for comparison with clinicopathological data through statistical analysis with Man Whitney U and Log-Rank tests. In addition, clinical value of MMP13 levels for diagnosis was evaluated by receiver operating characteristic (ROC) test. Results: The serum level of MMP-13 in patients (>250 pg/ml) was significantly higher than in the control group (<100 pg/ml) (p value=0.004). Also the results showed a significant correlation between MMP-13 serum levels with tumor stage (p value = 0.003), depth of tumor invasion (p value=0.008), involvement of lymph nodes (p value = 0.011), tumor size (p value = 0.018) and survival time. While there were no significant correlation with grade and location of tumors. ROC analysis showed that MMP-13 level is an accurate diagnostic marker especially to differentiate pre-invasive/ invasive lesions from normal controls (sensitivity and specificity: 100%). Conclusions: These findings indicate a potential clinical significance of serum MMP13 measurement for early detection and prognostic assessment in ESCC patients.

• BLOOD RESEARCH
• /
• v.53 no.4
• /
• pp.320-324
• /
• 2018

Background Recent studies have devoted much attention to non-protein-coding transcripts in relation to a wide range of malignancies. MALAT1, a long non-coding RNA, has been reported to be associated with cancer progression and prognosis. Thus, we here determined MALAT1 gene expression in chronic lymphocytic leukemia (CLL), a genetically heterogeneous disease, and explored its possible relationships with cytogenetic abnormalities. Methods MALAT1 expression level was evaluated using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) on blood mononuclear cells from 30 non-treated CLL patients and 30 matched healthy controls. Cytogenetic abnormalities were determined in patients by fluorescence in situ hybridization (FISH). Results MALAT1 expression level was up-regulated in the CLL group compared to healthy controls (P=0.008). Del13q14, followed by Del11q22, were the most prevalent cytogenetic abnormalities. We found no association between the FISH results and MALAT1 expression in patients. Conclusion Altered expression of MALAT1 is associated with CLL development. Further investigations are required to assess the relationship between this long non-coding RNA and CLL patient survival and prognosis.

• The Korean Journal of Physiology and Pharmacology
• /
• v.27 no.3
• /
• pp.197-208
• /
• 2023

Dysregulation of certain long non-coding RNAs may facilitate tumor initiation and progression. However, numerous carcinogenesis-related long noncoding RNAs have not been characterized. The goal of this study was to elucidate the role of LINC00562 in gastric cancer (GC). The expression of LINC00562 was analyzed using real-time quantitative PCR and Western blotting. The proliferative capacity of GC cells was determined using Cell Counting Kit-8 and colony-formation assays. The migration of GC cells were evaluated using wound-healing assays. The apoptosis of GC cells was assessed by measuring the expression levels of apoptosis-related proteins (Bax and Bcl-2). Xenograft models in nude mice were constructed for in vivo functional analysis of LINC00562. The binding relationship between miR-4636 and LINC00562 or adaptor protein complex 1 sigma 3 (AP1S3), obtained from public databases, was confirmed using dual-luciferase and RNA-binding protein immunoprecipitation experiments. LINC00562 was expressed in GC cells at high levels. Knockdown of LINC00562 repressed GC cell growth and migration, promoted apoptosis in vitro, and inhibited tumor growth in nude mouse models. LINC00562 directly targeted miR-4636, and miR-4636 depletion restored the GC cell behavior inhibited by LINC00562 absence. AP1S3, an oncogene, binds to miR-4636. MiR-4636 downregulation increased AP1S3 level, restoring GC cell malignant behaviors inhibited by AP1S3 downregulation. Thus, LINC00562 exerts carcinogenic effects on GC development by targeting miR-4636-mediated AP1S3 signaling.

• Biomolecules & Therapeutics
• /
• v.31 no.6
• /
• pp.682-691
• /
• 2023

Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed EGF-induced cell proliferation and anchorage-independent colony growth. EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3β, and p-NFκB expression. Treatment with MK-2206, an AKT pharmacological inhibitor, suppressed EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin carcinogenesis.

• The Korean Journal of Physiology and Pharmacology
• /
• v.28 no.3
• /
• pp.265-273
• /
• 2024

This study aims to explore possible effect of RNA polymerase I subunit D (POLR1D) on proliferation and angiogenesis ability of colorectal cancer (CRC) cells and mechanism herein. The correlation of POLR1D and Yin Yang 1 (YY1) expressions with prognosis of CRC patients in TCGA database was analyzed. Quantitative realtime polymerase chain reaction (qRT-PCR) and Western blot were applied to detect expression levels of POLR1D and YY1 in CRC cell lines and CRC tissues. SW480 and HT-29 cells were transfected with si-POLR1D or pcDNA3.1-POLR1D to achieve POLR1D suppression or overexpression before cell migration, angiogenesis of human umbilical vein endothelial cells were assessed. Western blot was used to detect expressions of p38 MAPK signal pathway related proteins and interaction of YY1 with POLR1D was confirmed by dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP). TCGA data showed that both POLR1D and YY1 expressions were up-regulated in CRC patients. High expression of POLR1D was associated with poor prognosis of CRC patients. The results showed that POLR1D and YY1 were highly expressed in CRC cell lines. Inhibition or overexpression of POLR1D can respectively suppress or enhance proliferation and angiogenesis of CRC cells. YY1 inhibition can suppress CRC progression and deactivate p38 MAPK signal pathway, which can be counteracted by POLR1D overexpression. JASPAR predicted YY1 can bind with POLR1D promoter, which was confirmed by dual luciferase reporter gene assay and ChIP. YY1 transcription can up-regulate POLR1D expression to activate p38 MAPK signal pathway, thus promoting proliferation and angiogenesis ability of CRC cells.

• Annals of Hepato-Biliary-Pancreatic Surgery
• /
• v.27 no.2
• /
• pp.180-188
• /
• 2023

Backgrounds/Aims: The present study looked at the role of radical surgery in gallbladder cancers (GBC) with limited metastatic disease. Methods: The retrospective observational study was conducted to screen the database from 1st January 2010 to 31st December 2019. Patients of GBC found to have low-volume metastatic disease upon surgical exploration were included. Results: Of the 1,040 patients operated for GBC, 234 patients had low-volume metastatic disease (microscopic disease in station 16b1 node or N2 disease isolated port-site metastases, or low burden peritoneal disease with deposits less than 1 cm, in adjacent omentum or adjacent diaphragm or Morrison's pouch or a solitary discontinuous liver metastasis in adjacent liver parenchyma) detected intraoperative. Of these, 62 patients underwent radical surgery for R-0 metastatic disease followed by systemic therapy, while the remaining 172 patients did not undergo radical surgery and were given palliative systemic chemotherapy. Patients who underwent radical surgery had significantly superior overall survival (19 months versus 12 months, p < 0.01) and superior progression-free survival (10 months versus 5 months, p < 0.01) when compared to the rest. This difference in survival was more significant amongst patients when operated on after neoadjuvant chemotherapy. Regression analysis showed that a sub-group of patients with incidental GBC with limited metastases showed more favorable outcomes with radical surgery. Conclusions: Authors suggest a possible role for radical treatment of advanced GBC with a limited metastatic burden. Neoadjuvant chemotherapy can be used for preferentially selecting patients of favorable disease biology for curative treatment.

• Journal of Gastric Cancer
• /
• v.24 no.4
• /
• pp.406-419
• /
• 2024

Purpose: This study aimed to evaluate the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, including overall survival (OS), remission, and factors associated with an aggressive disease course. Materials and Methods: Medical records of 153 patients diagnosed with gastric MALT lymphoma between 2013 and 2020 were retrospectively reviewed. Patients experiencing relapse, progression, high-grade transformation, or residual diseasewere included in the aggressive group and were compared with those in the indolent group. Additionally, the endoscopic findings of Helicobacter pylori-negative patients were reviewed. Results: Patient characteristics were as follows: mean age (56.9±11.2 years), sex (male, 51.0%), H. pylori infection (positive, 79.7%), endoscopic location (distal, 89.5%), endoscopic feature (superficial, 89.5%), clinical stage (stage I, 92.8%), invasion depth by endoscopic ultrasound (mucosa, n=115, 75.7%), and bone marrow result (no involvement, n=77, 100.0%). The median follow-up period was 59 months (mean, 61; range, 36-124) and the continuous remission period (n=149) was 51 months (mean, 50; range, 3-112). The 5-year survival rate was 97.7% while the 5-year continuous remission was 88.3%. Factors associated with the patients in the aggressive group were old age, sex(male), and clinical stage II or higher. H. pylori-negative patients' endoscopy revealed a high incidence of atrophic gastritis in the antrum. Conclusions: The long-term prognosis of gastric MALT lymphoma appears indolent and is indicated by the 5-year OS and continuous remission rates. Aggressive disease courses are associated with old age, sex (male), and clinical stage II or higher, but are not related to OS.

• Clinical Nutrition Research
• /
• v.11 no.3
• /
• pp.183-193
• /
• 2022

We investigated the predictors of survival in patients with advanced BTC according to their baseline nutritional status estimated by the Nutritional Risk Screening (NRS)-2002. From September 2006 to July 2017, we reviewed the data of 601 inpatients with BTC. Data on demographic and clinical parameters was collected from electronic medical records, and overall survival (OS) and progression-free survival were analyzed using the Kaplan-Meier method and the stepwise Cox regression analysis. Patients with an NRS-2002 score of ≤ 2, 3, and ≥ 4 were respectively classified as "no risk," "moderate risk," "high risk." Following initial NRS-2002 score, 333 patients (55%) were classified as "no-risk," 109 patients (18%) as "moderate-risk," and 159 patients (27%) as "high-risk." Survival analysis demonstrated significant differences in the median OS: "no-risk": 12.6 months (95% confidence interval [CI], 11.5-13.7); "moderate-risk": 6.1 months (95% CI, 4.3-8.0); and "high-risk": 3.9 months (95% CI, 3.2-4.6) (p < 0.001). NRS-2002 score was an independent factor for OS (hazard ratio [HR], 1.616 for "moderate-risk", 95% CI, 1.288-2.027, p < 0.001; HR, 2.121 for "high-risk", 95% CI, 1.722-2.612, p < 0.001), along with liver metastasis, peritoneal seeding, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, cholesterol, carcinoembryonic antigen, and carbohydrate antigen 19-9. In conclusion, baseline NRS-2002 is an appropriate method for discriminating those who are already malnourished and who have poor prognosis in advanced BTC patient. Significance of these results merit further validation to be integrated in the routine practice to improve quality of care in BTC patients.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.4
• /
• pp.2283-2288
• /
• 2013

Background: Efficacy of chemotherapy plus bevacizumab has been shown in patients with metastatic colorectal cancer (mCRC) compared with chemotherapy alone. The aim of the present study was to evaluate the efficacy and safety of FOLFIRI or XELIRI regimens in combination with bevacizumab for mCRC patients in a first-line setting. Materials and Methods: A total of 132 patients with previously untreated and histologically confirmed mCRC were included. They were treated with either FOLFIRI-Bevacizumab (Bev) or XELIRI-Bev according to physician preference. The efficacy and safety of the two regimens were compared. Results: Between 2006 and 2010, 68 patients were treated with the XELIRI-Bev regimen, while the remaining 64 patients received the FOLFIRI-Bev regimen. The median age was 58.5 years (53.6 years in the FOLFIRI-Bev and 59.7 years in the XELIRI-Bev arm, p=0.01). Objective response rate was 51.6% for FOLFIRI-Bev versus 41.2% for XELIRI-Bev (p=0.38). At the median follow-up of 24.5 months, the median progression-free survival (PFS) was not different between two groups (14.2 months in FOLFIRI-Bev vs. not reached in the XELIRI-Bev, p=0.30). However, median overall survival time for the FOLFIRI-Bev arm was better than that for patients treated with XELIRIBev, but these differences was not statistically significant (37.8 months vs. 28.7 months, respectively, p=0.58). Most commonly reported grade 3-4 toxicities (FOLFIRI-Bev vs XELIRI-Bev) were nausea/vomiting (7.8% vs. 14.7%, p=0.27), diarrhea (10.9% vs 22.1%, p=0.10), hand-foot syndrome (0% vs 8.8%, p=0.02) and neutropenia (18.7% vs 27.9%, p=0.22). Conclusion: Our results showed that FOLFIRI-Bev and XELIRI-Bev regimens were similarly effective treatments in a first-line setting for patients with untreated mCRC, with manageable adverse event profiles.