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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 5150-5150
    Abstract: Background: JMJD3 has been known to play important roles in transcriptional regulation and cell proliferation by demethylating histone3 lysin27 (H3K27) in various cancers. However, the mechanism underlying JMJD3-mediated transcriptional regulation and the relation with prognosis were unclear in colorectal carcinoma. Here, we investigated the expression of JMJD3 in clinical samples and the function of JMJD3 in colorectal carcinoma cell lines. Methods: Quantitative real-time PCR were performed to check the expression of JMJD3 mRNA using the carcinoma and normal colorectal tissue in 14 colorectal carcinoma patients who underwent a curative surgery. In vitro analysis, we investigated the expression of JMJD3 in colorectal carcinoma cell lines by Western Blotting, and we knocked down the expression of JMJD3 by using small interfering RNA in Colo201 and colo320. The influence of JMJD3 on cell growth, apoptosis and cell cycle was assessed by growth assay, apoptosis assay and cell cycle analysis. We checked the changes of cell cycle related genes by real time PCR. Results: In clinical samples, the expression of JMJD3 in carcinoma tissue was significantly lower than in normal tissue (P=0.02). In vitro analysis, we knocked down the expression of JMJD3 by siRNA targeting JMJD3 and checked the reduction on mRNA and protein level. Knockdown of JMJD3 significantly increased cell proliferation (P=0.02), reduced apoptosis (P=0.003), and increased G2/M phase population (P = 0.05) which was detected by FACS. Moreover, knockdown of JMJD3 significantly decreased the expression of p15INK4B in quantitative real-time PCR. Conclusion: We showed the expression of JMJD3 in carcinoma tissue was lower than in normal tissue and demonstrated that the down-regulation of JMJD3 resulted in the increase of cell proliferation, acceleration of cell cycle and anti-apoptosis in vitro analysis. These results suggest that JMJD3 is a tumor suppressor gene for colorectal carcinoma. Note: This abstract was not presented at the meeting. Citation Format: Ryuma Tokunaga, Shigeki Nakagawa, Yasuo Sakamoto, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Takatsugu Ishimoto, Shiro Iwagami, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. JMJD3 suppresses progression of colorectal carcinoma by regulating cell cycle and anti-apoptosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5150. doi:10.1158/1538-7445.AM2014-5150
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. e15035-e15035
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. e15035-e15035
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. e15010-e15010
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e15010-e15010
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 118-118
    Abstract: 118 Background: Local failure after chemoradiotherapy (CRT) remains a major problem for patients with esophageal squamous cell carcinoma (ESCC), and there are few curative treatment options available in such cases except salvage esophagectomy. The aim of this study is to demonstrate the clinical efficacy and safety of endoscopic submucosal dissection as a salvage therapy (salvage ESD) for local failure after CRT. Methods: Between 2007 and 2011, 66 patients underwent ESD for superficial ESCC in our hospital. Five of these patients underwent salvage ESD for local failure after CRT, and were reviewed retrospectively. They were treated with CRT, consisting of 60 Gy irradiation and concurrent chemotherapy. The indications for salvage ESD were as follows: 1) absence of lymph-node or distant metastasis after CRT; 2) superficial and endoscopically resectable lesion after CRT; 3) refusal by patient to undergo salvage esophagectomy; 4) written informed consent. Salvage ESD was performed using a flush knife or hook knife with a hyaluronic acid injection into the submucosal layer. Results: The baseline stage before CRT was as follows: T1b/T2/T3 in 3/1/1, N0/1 in 4/1, and M0/1 in 4/1 patients, respectively. These 5 patients had histologically proven local failure, and the stage after CRT was as follows: T1a/T1b in 1/4, N0/1 in 5/0, and M0/1 in 5/0 patients, respectively. Salvage ESD was performed in all patients who had en bloc resection with no complications and pathologically R0 resection. In 5 patients, 2 had a pT1a lesion, and 3 had a pT1b lesion. 1 lesion recurred in other site 3 months after salvage ESD, which was resected successfully by a second ESD procedure. Conclusions: Salvage ESD is an available option for patients with local failure after CRT for ESCC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 420-420
    Abstract: Objective: DNA methylation is a fundamental epigenetic process that modulates gene expression. Cancer cells exhibit two types of DNA methylation alterations: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Although the base 5-methylcytosine (5mc) and the DNA methyltransferase (DNMT) family of enzymes that catalyze DNA methylation are well-studied, the mechanisms of DNA demethylation are poorly understood. The Ten-eleven translocation (Tet) family of enzymes (Tet1, Tet2, and Tet3) has been implicated in DNA demethylation. These enzymes possess the dioxygenase activity and convert 5-mC to 5-hydroxymethylcytosine (5-hmC). Frequent Tet mutational inactivation or reduction has been reported to associate with decreased 5-hmC levels in various types of myeloid leukemia and melanoma. However, the status of 5hmC and Tet expression in esophageal squamous cell carcinoma (ESCC) remains still unknown. Method: We analyzed the 5-hmC status in DNA from ESCC frozen tissues utilizing the ELISA test, and 5-hmC expression was evaluated by immunohistochemistry. We next examined the expression levels of Tet family mRNA in both normal and tumor tissues by RT-qPCR. Results: 5-hmC level was significantly lower in ESCC than in paired normal tissue in ELISA test (n=33, P & lt;0.0001). The similar result was observed in immunohistochemistry. We found that the Tet2 mRNA expression was significantly lower in ESCCs than paired normal tissues (n=32, P & lt;0.0001). The expression level of Tet2 mRNA was significantly associated with the 5hmC status (n=31, r=0.54, P=0.0085). Finally, 5-hmC status did not correlate with overall survival (P = 0.65). Conclusion: The 5hmC expression was decreased in ESCC tissues, and was associated with Tet2 expression level, suggesting that 5hmC and Tet2 might play a crucial role in the development of ESCCs. Citation Format: Asuka Murata, Yoshifumi Baba, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Takatsugu Ishimoto, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. Tet family proteins and 5-hydroxymethylcytosine in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 420. doi:10.1158/1538-7445.AM2014-420
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 41-41
    Abstract: 41 Background: DNA methylation is a major epigenetic mechanism in X-chromosome inactivation, imprinting and repression of transposable elements and endogenous retroviral sequences. Global DNA hypomethylation appears to play an important role in genomic instability, leading to cancer development. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of global DNA methylation level. Smoking and alcohol is extremely important as the etiology of esophageal squamous cell carcinoma. Nonetheless, whether or not smoking and alcohol affect LINE-1 methylation level in normal esophageal epithelium of esophageal cancer patients remains uncertain. Methods: We quantified LINE-1 methylation of normal esophageal mucosa using pyrosequencing technology in 118 resected esophageal squamous cell carcinomas. The data on smoking (Brinkman index, absence or presence) and alcohol amount are available in all cases. We excluded preoperatively treated cases. Results: LINE-1 methylation in normal esophageal epithelium of esophageal cancer patients ranged from 57.1 to 92.8 of 0-100 scale (N=118; mean 81.2; median 80.0; standard deviation 7.2). LINE-1 methylation level (continuous variable) was significantly associated with Brickman index (continuous variable) (r=0.12, p=0.0002); heavy smoker had lower LINE-1 methylation level of normal esophageal mucosa. LINE-1 methylation level was lower in patients with smoking history (mean 79.7) than in patients without smoking history (mean 83.2) (p=0.034). Alcohol assumption was not associated with LINE-1 methylation level (r=0.003, p=0.58). Conclusions: Smoking was associated with LINE-1 hypomethylation in esophageal normal epithelium, suggesting the possibility of epigenetic field effects caused by cigarette in esophageal tumorigenesis. Considering that DNA methylation alterations are reversible and can thus be targets for chemoprevention, our findings may have clinical implication.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. 209-209
    Abstract: 209 Background: It is sometimes difficult to exactly measure maximum diameters of tumor after chemotherapy in esophageal cancer. Richard et al. proposed PET Response Criteria in Solid Tumor (PERCIST) for assessing response of tumor after chemotherapy by PET in 2009. The first purpose is to investigate the utility of PERCIST after neoadjvant chemotherapy in esophageal cancer. The second purpose is to clarify the utility of modified PERCIST of which we use the SUV of normal (non-cancerous) esophagus as a reference of comparison for diagnosing complete response (CR) instead of the right lobe liver SUV. Methods: The clinicopathological data of the 71 esophageal cancer patients who received neoadjuvant chemotherapy (DCF) and underwent curative resection from November 2008 to May 2012 were collected. Among them, we compared pathological grade with PERCIST of the 26 esophageal cancer patients who were examined by PET before and after chemotherapy. Furthermore we investigated which reference of comparison is appropriate for diagnosing complete response between the right lobe of liver (L group) and normal esophagus (E group). Results: We could measure the tumor size of all cases after chemotherapy by PERCIST although 6 cases could not be assessed by RECIST. All of the 6 cases which were diagnosed as stable disease or progressive disease by PERCIST were pathological grade1a. The cases of complete response are 7 cases in L group and 3 cases in esophageal cases. Among the complete response cases in L group, 1 case were pathological grade1 a and 2 cases were grade 2 although all the complete response cases in E group were pathological grade 3. One case of L group relapsed after curative resection although there was no recurrent case in E group. Conclusions: The esophageal cancer patients often have history of massive alcohol intake or liver damage caused by viral hepatitis or fatty liver. Although PERCIST is useful for evaluating the effect of neoadjuvant chemotherapy of esophageal cancer, it is better to use normal esophagus as a comparison standard for diagnosing complete response.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 26-26
    Abstract: 26 Background: Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of global DNA methylation level. LINE-1 methylation is a useful marker for predicting cancer prognosis and monitoring efficacy of adjuvant therapy. Esophageal squamous cell carcinoma, the major histological type of esophageal cancer in East Asian countries, is one of the most aggressive malignant tumors. Nonetheless, prognostic significance of LINE-1 hypomethylaiton in esophageal cancer remains uncertain. Methods: Using 217 curatively resected esophageal squamous cell carcinomas, we quantified LINE-1 methylation using bisulfite-PCR-pyrosequencing assay. Cox proportional hazards model was used to calculate mortality hazard ratio (HR), adjusted for clinical, epidemiologic, and pathological variables. Results: Esophageal cancers showed significantly lower LINE-1 methylation level compared to matched normal esophageal mucosa (p 〈 0.0001; N=50). Tumoral LINE-1 methylation ranged from 24.8 to 91.8 of 0-100 scale (N=217; mean 64.5; median 65.0; standard deviation 12.8). LINE-1 hypomethylation was significantly associated with disease-free survival [log-rank p=0.0008; univariate HR= 2.31, 95% confidence interval (CI) 1.38-3.84, p=0.0017; multivariate HR=1.81, 95% CI 1.06-3.05, p=0.031] and overall survival (log-rank p=0.0013; univariate HR=2.21, 95% CI 1.33-3.60, p=0.0026; multivariate HR=1.87, 95% CI 1.12-3.08, p=0.018] . Conclusions: LINE-1 hypomethylation in esophageal cancer is associated with shorter survival, suggesting its role as a prognostic biomarker. Given that epigenetic changes, including DNA methylation alterations, are reversible and can thus be targets for therapy or chemoprevention, our findings may have considerable clinical implications.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 9
    In: Chest, Elsevier BV, Vol. 130, No. 1 ( 2006-07), p. 22-29
    Type of Medium: Online Resource
    ISSN: 0012-3692
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2006
    detail.hit.zdb_id: 2007244-2
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  • 10
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 54, No. 5 ( 2022-05), p. 560-572
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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