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Methylation rectal cancer

Tsuyoshi Hamada, Yin Cao, Zhi Rong Qian, Yohei Masugi, Jonathan A Nowak, Juhong Yang, Mingyang Song, Kosuke Mima, Keisuke Kosumi, Li Liu, Yan Shi, Annacarolina da Silva, Mancang Gu, Wanwan Li, NaNa Keum, Xuehong Zhang, Kana Wu, Jeffrey A Meyerhardt, Edward L Giovannucci, Marios Giannakis, Scott J Rodig, Gordon J Freeman, Daniel Nevo, Molin Wang, Andrew T Chan, Charles S Fuchs, Reiko Nishihara, Shuji Ogino
Purpose Blockade of the programmed cell death 1 (PDCD1, PD-1) immune checkpoint pathway can improve clinical outcomes in various malignancies. Evidence suggests that aspirin (a widely used nonsteroidal anti-inflammatory drug) not only prolongs colorectal cancer survival, but can also activate T cell-mediated antitumor immunity and synergize with immunotherapy through inhibition of prostaglandin E2 production. We hypothesized that the survival benefit associated with aspirin might be stronger in colorectal carcinoma with a lower CD274 (PDCD1 ligand 1, PD-L1) expression level that resulted in lower signaling of the immune checkpoint pathway...
April 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Keisuke Kosumi, Yohei Masugi, Juhong Yang, Zhi Rong Qian, Sun A Kim, Wanwan Li, Yan Shi, Annacarolina da Silva, Tsuyoshi Hamada, Li Liu, Mancang Gu, Tyler S Twombly, Yin Cao, David A Barbie, Katsuhiko Nosho, Hideo Baba, Wendy S Garrett, Jeffery A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Shuji Ogino, Reiko Nishihara
Evidence suggests that activation of autophagy in neoplastic cells potentiates antitumor immunity through cross-presentation of tumor-associated antigens to T cells and release of immune mediators. The SQSTM1 (sequestosome 1, p62) protein is degraded by activated autophagy, and might enhance immune response to tumor cells. We hypothesized that tumor SQSTM1 expression level might be inversely associated with T-cell densities in colorectal carcinoma tissue. We evaluated tumor SQSTM1 expression by immunohistochemistry in 601 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study...
2017: Oncoimmunology
Yang Hua, Xiukun Ma, Xianglong Liu, Xiangfei Yuan, Hai Qin, Xipeng Zhang
AIM: Rectal adenocarcinoma (READ) is a malignancy cancer with the high morbidity and motility worldwide. Our study aimed to explore the potential pathogenesis of READ through integrated analysis of gene expression profiling and DNA methylation data. METHODS: The miRNA, mRNA expression profiling and corresponding DNA methylation data were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs/ miRNAs/methylated regions (DEmRNA/DEmiRNAs) were identified in READ...
2017: PloS One
K Yokoi, K Yamashita, S Ishii, T Tanaka, N Nishizawa, A Tsutsui, H Miura, H Katoh, T Yamanashi, M Naito, T Sato, T Nakamura, M Watanabe
BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) for advanced rectal cancer (RC) is a well-evidenced therapy; however, some RC patients have no therapeutic response. Patient selection for NCRT so that non-responsive patients are excluded has been subjective. To date, no molecular markers indicating radiation sensitivity have been reported. METHODS: We irradiated six colorectal cancer (CRC) cell lines and identified HCT116 cells as radiation-sensitive and HCT15 and DLD-1 cells as radiation resistant...
April 11, 2017: British Journal of Cancer
Raaj S Mehta, Mingyang Song, Reiko Nishihara, David A Drew, Kana Wu, Zhi Rong Qian, Teresa T Fung, Tsuyoshi Hamada, Yohei Masugi, Annacarolina da Silva, Yan Shi, Wanwan Li, Mancang Gu, Walter C Willett, Charles S Fuchs, Edward L Giovannucci, Shuji Ogino, Andrew T Chan
BACKGROUND & AIMS: Western and prudent dietary patterns have been associated with higher and lower risks of colorectal cancer (CRC), respectively. However, little is known about associations between dietary patterns and specific anatomic subsite or molecular subtypes of CRC. METHODS: We used multivariable Cox proportional hazards models to examine associations between Western and prudent dietary patterns and CRC risk in the Health Professionals Follow-up Study and Nurses' Health Study...
February 26, 2017: Gastroenterology
Chang Hyun Kim, Jung Wook Huh, Hyeong Rok Kim, Young Jin Kim
BACKGROUND AND AIMS: The CpG island methylator phenotype (CIMP) is found in approximately 30% of colorectal cancer (CRC) cases. However, the role of CIMP status in predicting oncologic outcomes in curatively resected CRC is still unclear. STUDY: Between January 2006 and December 2006, we retrospectively reviewed 157 consecutive patients who underwent curative surgery for CRC. Prognostic significance of CIMP status was evaluated using reverse transcriptase-polymerase chain reaction...
January 14, 2017: Journal of Gastroenterology and Hepatology
Fiona C Malcomson, Naomi D Willis, Iain McCallum, Long Xie, Idoia Ibero-Baraibar, Wing C Leung, Seamus Kelly, D Michael Bradburn, Nigel J Belshaw, Ian T Johnson, John C Mathers
BACKGROUND: Hyperactive Wnt signaling is frequently observed in colorectal cancer. Higher intakes of dietary fiber [nondigestible carbohydrates (NDCs)] and the fermentation product butyrate are protective against colorectal cancer and may exert their preventative effects via modulation of the Wnt pathway. OBJECTIVES: We investigated the effects of supplementing healthy individuals with 2 NDCs [resistant starch (RS) and polydextrose] on fecal calprotectin concentrations and Wnt pathway-related gene expression...
February 2017: American Journal of Clinical Nutrition
Tomomitsu Tahara, Ichiro Hirata, Naoko Nakano, Mitsuo Nagasaka, Yoshihito Nakagawa, Tomoyuki Shibata, Naoki Ohmiya
INTRODUCTION: Aberrant DNA methylation frequently occurs in the inflammatory mucosa in ulcerative colitis (UC) and is involved in UC-related tumorigenesis. We performed comprehensive DNA methylation profiling of the promoter regions of the inflamed rectal mucosae of patients with UC. DESIGN: The methylation status of the promoter CpG islands (CGIs) of 45 cancer/inflammation or age-related candidate genes and the LINE1 repetitive element were examined in the colonic mucosae of 84 cancer-free patients with UC by bisulfite pyrosequencing...
January 2017: Inflammatory Bowel Diseases
Ying Hu, Graeme H McIntosh, Richard K Le Leu, Roshini Somashekar, Xing Q Meng, Geetha Gopalsamy, Libby Bambaca, Ross A McKinnon, Graeme P Young
Se and green tea have been shown in epidemiological, observational and preclinical studies to be inversely related to the risk of developing colorectal cancer (CRC). However, there are limited studies to evaluate their regulatory effects on genes/proteins that relate to CRC oncogenesis in human subjects, such as selenoproteins, WNT signalling pathway, inflammation and methylation. This study examined the effects of supplementation of Se using Brazil nuts and green tea extract (GTE) capsules, alone and in combination, on targeted biomarkers...
December 2016: British Journal of Nutrition
Ruoxu Dou, Reiko Nishihara, Yin Cao, Tsuyoshi Hamada, Kosuke Mima, Atsuhiro Masuda, Yohei Masugi, Yan Shi, Mancang Gu, Wanwan Li, Annacarolina da Silva, Katsuhiko Nosho, Xuehong Zhang, Jeffrey A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis...
November 2016: Cancer Immunology Research
Jiufeng Wei, Guodong Li, Jinning Zhang, Yuhui Zhou, Shuwei Dang, Hongsheng Chen, Qiong Wu, Ming Liu
DNA methylation was regarded as the promising biomarker for rectal cancer diagnosis. However, the optimal methylation biomarkers with ideal diagnostic performance for rectal cancer are still limited. To identify new molecular markers for rectal cancer, we mapped DNA methylation and transcriptomic profiles in the six rectal cancer and paired normal samples. Further analysis revealed the hypermethylated probes in cancer prone to be located in gene promoter. Meanwhile, transcriptome analysis presented 773 low-expressed and 1,161 over-expressed genes in rectal cancer...
September 20, 2016: Oncotarget
Fang Zhao, Ekaterina Olkhov-Mitsel, Theodorus van der Kwast, Jenna Sykes, Darko Zdravic, Vasundara Venkateswaran, Alexandre R Zlotta, Andrew Loblaw, Neil E Fleshner, Laurence Klotz, Danny Vesprini, Bharati Bapat
PURPOSE: Patients with prostate cancer on active surveillance are monitored by repeat prostate specific antigen measurements, digital rectal examinations and prostate biopsies. A subset of patients on active surveillance will later reclassify with disease progression, prompting definitive treatment. To minimize the risk of under treating such patients on active surveillance minimally invasive tests are urgently needed incorporating biomarkers to identify patients who will reclassify. MATERIALS AND METHODS: We assessed post-digital rectal examination urine samples of patients on active surveillance for select DNA methylation biomarkers that were previously investigated in radical prostatectomy specimens and shown to correlate with an increasing risk of prostate cancer...
February 2017: Journal of Urology
Veronika Vymetalkova, Pavel Vodicka, Barbara Pardini, Fabio Rosa, Miroslav Levy, Michaela Schneiderova, Vaclav Liska, Ludmila Vodickova, Torbjörn K Nilsson, Sanja A Farkas
AIM: The aim of the present study is to address a genome-wide search for novel methylation biomarkers in the rectal cancer (RC), as only scarce information on methylation profile is available. MATERIALS & METHODS: We analyzed methylation status in 25 pairs of RC and adjacent healthy mucosa using the Illumina Human Methylation 450 BeadChip. RESULTS: We found significantly aberrant methylation in 33 genes. After validation of our results by pyrosequencing, we found a good agreement with our findings...
September 2016: Epigenomics
Kosuke Mima, Jonathan A Nowak, Zhi Rong Qian, Yin Cao, Mingyang Song, Yohei Masugi, Yan Shi, Annacarolina da Silva, Mancang Gu, Wanwan Li, Tsuyoshi Hamada, Xuehong Zhang, Kana Wu, Jeffrey A Meyerhardt, Hideo Baba, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Shuji Ogino, Reiko Nishihara
Colorectal tumors arise with genomic and epigenomic alterations through interactions between neoplastic cells, immune cells, and microbiota that vary along the proximal to distal axis of colorectum. Long interspersed nucleotide element-1 (LINE-1) hypomethylation in colorectal cancer has been associated with worse clinical outcome. Utilizing 1,317 colon and rectal carcinoma cases in two U.S.-nationwide prospective cohort studies, we examined patient survival according to LINE-1 methylation level stratified by tumor location...
August 23, 2016: Oncotarget
Martha L Slattery, Jennifer S Herrick, Lila E Mullany, Erica Wolff, Michael D Hoffman, Daniel F Pellatt, John R Stevens, Roger K Wolff
MiRNAs regulate gene expression by post-transcriptionally suppressing mRNA translation or by causing mRNA degradation. It has been proposed that unique miRNAs influence specific tumor molecular phenotype. In this paper, we test the hypotheses that miRNA expression differs by tumor molecular phenotype and that those differences may influence prognosis. Data come from population-based studies of colorectal cancer conducted in Utah and the Northern California Kaiser Permanente Medical Care Program. A total of 1893 carcinoma samples were run on the Agilent Human miRNA Microarray V19...
August 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Yohei Masugi, Reiko Nishihara, Juhong Yang, Kosuke Mima, Annacarolina da Silva, Yan Shi, Kentaro Inamura, Yin Cao, Mingyang Song, Jonathan A Nowak, Xiaoyun Liao, Katsuhiko Nosho, Andrew T Chan, Marios Giannakis, Adam J Bass, F Stephen Hodi, Gordon J Freeman, Scott Rodig, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
OBJECTIVE: Evidence suggests that CD274 (programmed death-ligand 1, B7-H1) immune checkpoint ligand repress antitumour immunity through its interaction with the PDCD1 (programmed cell death 1, PD-1) receptor of T lymphocytes in various tumours. We hypothesised that tumour CD274 expression levels might be inversely associated with T-cell densities in colorectal carcinoma tissue. DESIGN: We evaluated tumour CD274 expression by immunohistochemistry in 823 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study...
May 5, 2016: Gut
Jeong Mo Bae, Jung Ho Kim, Gyeong Hoon Kang
CONTEXT: -Colorectal cancer is a heterogeneous disease entity with 3 molecular carcinogenesis pathways and 2 morphologic multistep pathways. Right-sided colon cancers and left-sided colon and rectal cancers exhibit differences in their incidence rates according to geographic region, age, and sex. A linear tendency toward increasing frequencies of microsatellite instability-high or CpG island methylator phenotype-high cancers in subsites along the bowel from the rectum to the cecum or the ascending colon accounts for the differences in tumor phenotypes associated with these subsites...
May 2016: Archives of Pathology & Laboratory Medicine
Xiaoliang Wang, Junwei Fan, Fudong Yu, Feifei Cui, Xing Sun, Lin Zhong, Dongwang Yan, Chongzhi Zhou, Guilong Deng, Bin Wang, Xiaosheng Qi, Shuyun Wang, Lei Qu, Biao Deng, Ming Pan, Jian Chen, Yupeng Wang, Guohe Song, Huamei Tang, Zongguang Zhou, Zhihai Peng
The aim of the present study was to determine whether MALL expression is associated with colon cancer progression and patient survival. MALL mRNA expression was reduced in the tumor tissues of 70% of the colon cancer patients and 75% of the rectal cancer patients as compared to their normal tissues. MALL protein was also significantly reduced in the tumor tissues of colon cancer patients (P < 0.001). Increased LOH and methylation of MALL was observed in tumor tissues as compared to normal tissues. Reduced MALL expression was associated with vessin invasion, disease recurrence and metastasis or death (P ≤ 0...
April 19, 2016: Oncotarget
Kosuke Mima, Reiko Nishihara, Juhong Yang, Ruoxu Dou, Yohei Masugi, Yan Shi, Annacarolina da Silva, Yin Cao, Mingyang Song, Jonathan Nowak, Mancang Gu, Wanwan Li, Teppei Morikawa, Xuehong Zhang, Kana Wu, Hideo Baba, Edward L Giovannucci, Jeffrey A Meyerhardt, Andrew T Chan, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
PURPOSE: Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2; a target of aspirin) produces inflammatory mediator prostaglandin E2 (PGE2), and contributes to colorectal neoplasia development. PTGS2-driven inflammatory responses can induce tumor expression of microRNA MIR21 (miR-21) that can increase local PGE2 level by downregulating PGE2-metabolizing enzymes. We hypothesized that the prognostic association of tumor MIR21 expression level in colorectal carcinoma might depend on inflammatory tumor microenvironment and be stronger in tumors expressing high-level PTGS2...
August 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Masakazu Miyake, Takashi Takeda, Naotsugu Haraguchi, Mamoru Uemura, Masataka Ikeda, Michihiko Miyazaki, Sakae Maeda, Kazuyoshi Yamamoto, Naoki Hama, Kazuhiro Nishikawa, Atsushi Miyamoto, Motohiro Hirao, Shoji Nakamori, Mitsugu Sekimoto
We report of a 74-year-old man with advanced rectal cancer invading the small intestine and bladder. Initially, 3 courses of neoadjuvant chemotherapy with FOLFIRI and cetuximab were administered. At the beginning of the 4 course, the patient experienced fever and dyspnea. Chest radiography and computed tomography showed ground-grass opacities in both lungs. He was diagnosed with interstitial pneumonia induced by irinotecan or cetuximab. Steroid pulse therapy consisting of methyl-prednisolone (1,000 mg/day; 3 days) with respiratory assist resulted in significant improvement, and prednisolone was continued while reducing the dose gradually...
November 2015: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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