• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1531-1537
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• 2014

Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene whose reduced expression may play an important role in the development and progression of esophageal squamous cell cancer (ESCC). The aim of this study was to investigate the clinical relevance of RUNX3 in ESCC patients and effects of overexpression on biological behaviour of Eca109 cells in vitro and in vivo. Immunohistochemistry was performed to detect the clinical relevance of RUNX3 and lymph node metastasis in 80 ESCC tissues and 40 non-cancerous tissues using the SP method. RT-PCR and Western blotting were applied to assess the RUNX3 level and verify the Eca109 cell line with stable overexpression. Localization of RUNX3 proteins was performed by cell immunofluorescence. CCK-8 and Scrape motility assays were used to determine proliferation and migration and the TUNEL assay to analyze cell apoptosis. Invasive potential was assessed in cell transwell invasion experiments. In nude mice, tumorigenesis in vivo was determined. Results showed decreased expression of RUNX3 in esophageal tissue to be significantly related to lymph node metastasis (LNM) (P<0.01). In addition, construction of a recombinant lentiviral vector and transfection into the human ESCC cell line Eca109 demonstrated that overexpression could inhibit cell proliferation, migration and invasion, and induce apoptosis. The in vivo experiments in mice showed tumorigenicity and invasiveness to be significantly reduced. Taken together, our studies indicate that underexpression of RUNX3 in human ESCC tissue is significantly correlated with progression. Restoration of RUNX3 expression significantly inhibits ESCC cells proliferation, migration, invasion and tumorigenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5789-5795
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• 2013

Background: The high mobility group box 1 (HMGB1) protein is a widespread nuclear protein present in most cell types. It typically locates in the nucleus and functions as a nuclear cofactor in transcription regulation. However, HMGB1 can also localize in the cytoplasm and be released into extracellular matrix, where it plays critical roles in carcinogenesis and inflammation. However, it remains elusive whether HMGB1 is relocated to cytoplasm in clear cell renal cell carcinoma (ccRCC). Methods: Nuclear and cytoplasmic proteins were extracted by different protocols from 20 ccRCC samples and corresponding adjacent renal tissues. Western blotting and immunohistochemistry were used to identify the expression of HMGB1 in ccRCC. To elucidate the potential mechanism of HMGB1 cytoplasmic translocation, HMGB1 proteins were enriched by immunoprecipitation and analyzed by mass spectrometry (MS). Results: The HMGB1 protein was overexpressed and partially localized in cytoplasm in ccRCC samples (12/20, 60%, p<0.05). Immunohistochemistry results indicated that ccRCC of high nuclear grade possess more HMGB1 relocation than those with low grade (p<0.05). Methylation of HMGB1 at lysine 112 in ccRCC was detected by MS. Bioinformatics analysis showed that post-translational modification might affect the binding ability to DNA and mediate its translocation. Conclusion: Relocation of HMGB1 to cytoplasm was confirmed in ccRCC. Methylation of HMGB1 at lysine 112 might the redistribution of this cofactor protein.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.1039-1042
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• 2012

Aim: Tanscatheter arterial embolization irrespective of with or without an anticancer agent and lipiodol has been controversial with regard to survival benefit. Therefore, we conducted a prospective study to analyze the effect of transcatheter arterial lipiodol chemoembolization (TACE) on the survival of HCC. Methods: A prospective study was conducted, and a total of 326 patients with primary liver cancer who were newly diagnosed were collected from January 2004 to January 2005 in Zhejiang Provincial People's Hospital of China. A univariate Cox's regression analysis was used to assess the survival of the HCC cases receiving TACE. Results: The duration of follow-up for the HCC patients treated with TACE ranged from 3 months to 60 months. For the overall patients, survival rate at 5 years was 42%. Both HBV Ag and HCV Ab positive patients showed significantly low survival rate at 5 years. The multivariate analysis revealed The IV TNM stage was related to an heavy increased risk of death of HCC patients, and Child C grade group showed a significant moderate increased risk. Conclusion: Our study showed TACE is associated with a better prognosis of HCC patients, and the HBV infection, TNM stage, Child-Pugh grade and number of TACE may influence the survival probability. Further TACE studies should be assess the quality of life of HCC patients, so as to provide more information for treatment of HCC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2207-2212
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• 2012

Overexpression of DNA methyltransferase 1 (DNMT1) has been detected in many cancers. Tobacco exposure is known to induce genetic and epigenetic changes in the pathogenesis of malignancy. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen present in tobacco smoke; however the detailed molecular mechanism of how NNK induces esophageal carcinogenesis is still unclear. We found that DNMT1 was overexpressed in ESCC tissues compared with paired non-cancerous tissues, the overexpression being correlated with smoking status and low expression of $RAR{\beta}$. The latter could be upregulated by NNK treatment in Het-1A cells, and the increased DNMT1 expression level reflected promoter hypermethylation and downregulation of retinoic acid receptor ${\beta}$($RAR{\beta}$). RNA interference mediated knockdown of DNMT1 resulted in promoter demethylation and upregulation of $RAR{\beta}$ in KYSE30 and TE-1 cells. 3-(4,5-Dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis demonstrated that NNK treatment in Het-1A cells could enhance cell proliferation and inhibit cell apoptosis in a dose-dependent manner. In conclusion, DNMT1 overexpression is correlated with smoking status and low expression of $RAR{\beta}$ in esophageal SCC patients. NNK could induce $RAR{\beta}$ promoter hypermethylation through upregulation of DNMT1 in esophageal squamous epithelial cells, finally leading to enhancement of cell proliferation and inhibition of apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5427-5433
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• 2013

5-Azacytidine (5-azaC) was originally identified as an anticancer drug (NSC102876) which can cause hypomethylation of tumor suppressor genes. To assess its effects on runt-related transcription factor 3 (RUNX3), expression levels and the promoter methylation status of the RUNX3 gene were assessed. We also investigated alteration of biologic behavior of esophageal carcinoma TE-1 cells. MTT assays showed 5-azaC inhibited the proliferation of TE-1 cells in a time and dose-dependent way. Although other genes could be demethylated after 5-azaC intervention, we focused on RUNX3 gene in this study. The expression level of RUNX3 mRNA increased significantly in TE-1 cells after treatment with 5-azaC at hypotoxic levels. RT-PCR showed 5-azaC at $50{\mu}M$ had the highest RUNX3-induction activity. Methylation-specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. Migration and invasion of TE-1 cells were inhibited by 5-azaC, along with growth of Eca109 xenografts in nude mice. In conclusion, we demonstrate that the RUNX3 gene can be reactivated by the demethylation reagent 5-azaC, which inhibits the proliferation, migration and invasion of esophageal carcinoma TE-1 cells.

• 건축역사연구
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• 제30권4호
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• pp.7-16
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• 2021

This study examines changes and features of provincial office buildings in Suwon and Chungju after relocation during Japanese occupation. Gyeonggi and Chungbuk provincial offices(Gwanchalbu) were relocated by Japan. Gyeonggi Provincial Office in Suwon used HwaseongHaenggung buildings and moved to Seoul in 1910. After relocation, most of HwaseongHaenggung buildings used for Suwon Governmental hospital(JaHye Uiwon). Suwongun Office, Suwon public elementary school, Japanese Military and Suwon Police station also used HwaseongHaenggung buildings with the Hospital. At first, Japan remodeled local government buildings for their use. Most of HwaseongHaenggung buildings had been destroyed to build new buildings since 1920s. Chungbuk Provincial office in Chungju used DongHeon building which is Chungju local government building and relocated to Cheongju in 1908. DongHeon building changed to Chungju county office after relocation. This building was renovated. Chungju county office moved to other site, this building was used for Chungju county conference room. During Japanese colonial period, Suwon local government buildings were destroyed and replaced with new Japanese style buildings. Chungju local government buildings were also renovated or destroyed.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5839-5843
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• 2014

Objective: The Zhejiang Provincial Cancer Prevention and Control Office collected cancer registration data during 2000 to 2009 from 6 cancer registries in Zhejiang province of China in order to analyze the cancer incidence. Methods: Descriptive analysis included cancer incidence stratified by sex, age and cancer site group. The proportions and cumulative rates of 10 common cancers in different groups were also calculated. Chinese population census in 1982 and Segi's population were used for calculating age-standardized incidence rates. The log-linear model was used for fitting to calculate the incidence trends. Results: The 6 cancer registries in Zhejiang province in China covered a total of 60,087,888 person-years during 2000 to 2009 (males 30,445,904, females 29,641,984). The total number of new cancer cases were 163,104 (males 92,982, females 70,122). The morphology verified cases accounted for 69.7%, and the new cases verified only by information from death certification accounted for 1.23%. The crude incidence rate in Zhejiang cancer registration areas was $271.5/10^5$ during 2000 to 2009 (male $305.41/10^5$, female $236.58/10^5$), age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were $147.1/10^5$ and $188.2/10^5$, the cumulative incidence rate (aged from 0 to 74) being 21.7%. The crude incidence rate was $209.6/10^5$ in 2000, and it increased to $320.20/10^5$ in 2009 (52.8%), with an annual percent change (APC) of 4.51% (95% confidence interval, 3.25%-5.79%). Age-specific incidence rate of 80-84 age group was achieved at the highest point of the incidence curve. Overall with different age groups, the cancer incidences differed, the incidence of liver cancer being highest in 15-44 age group in males; the incidence of breast cancer was the highest in 15-64 age group in females; the incidences of lung cancer were the highest in both males and females over the age of 65 years. Conclusions: Lung cancer, digestive system malignancies and breast cancer are the most common cancers in Zhejiang province in China requiring an especial focus. The incidences of thyroid cancer, prostate cancer, cervical cancer and lymphoma have increased rapidly. Prevention and control measures should be implemented for these cancers.

• The Korean Journal of Physiology and Pharmacology
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• 제23권1호
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• pp.89-89
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• 2019

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7719-7724
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• 2014

Background: Lymph node metastasis is believed to be a dependent negative prognostic factor of esophageal cancer. To explore detection methods with high sensitivity and accuracy for metastases to regional and distant lymph nodes in the clinic is of great significance. This study focused on clinical application of FDG PET/CT and contrast-enhanced multiple-slice helical computed tomography (MSCT) in lymph node staging of esophageal cancer. Materials and Methods: One hundred and fifteen cases were examined with enhanced 64-slice-MSCT scan, and FDG PET/CT imaging was conducted for neck, chest and upper abdomen within one week. The primary lesion, location and numbers of metastatic lymph nodes were observed. Surgery was performed within one week after FDG PET/CT detection. All resected lesions were confirmed histopathologically as the gold standard. Comparative analysis of the sensitivity, specificity, and accuracy based on FDG PET/CT and MSCT was conducted. Results: There were 946 lymph node groups resected during surgery from 115 patients, and 221 were confirmed to have metastasis pathologically. The sensitivity, specificity, accuracy of FDG PET/CT in detecting lymph node metastasis were 74.7%, 97.2% and 92.0%, while with MSCT they were 64.7%, 96.4%, and 89.0%, respectively. A significance difference was observed in sensitivity (p=0.030), but not the others (p>0.05). The accuracy of FDG PET/CT in detecting regional lymph node with or without metastasis were 91.9%, as compared to 89.4% for MSCT, while FDG PET/CT and MSCT values for detecting distant lymph node with or without metastasis were 94.4% and 94.7%. No significant difference was observed for either regional or distant lymph node metastasis. Additionally, for detecting para-esophageal lymph nodes metastasis, the sensitivity of FDG PET/CT was 72%, compared with 54.7% for MSCT (p=0.029). Conclusions: FDG PET/CT is more sensitive than MSCT in detecting lymph node metastasis, especially for para-esophageal lymph nodes in esophageal cancer cases, although no significant difference was observed between FDG PET/CT and MSCT in detecting both regional and distant lymph node metastasis. However, enhanced MSCT was found to be of great value in distinguishing false negative metastatic lymph nodes from FDG PET/CT. The combination of FDG PET/CT with MSCT should improve the accuracy in lymph node metastasis staging of esophageal cancer.