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https://www.readbyqxmd.com/read/28751909/simultaneous-methylation-level-assessment-of-hundreds-of-cpg-sites-by-targeted-bisulfite-pcr-sequencing-tbpseq
#1
Kyuheum Jeon, Byungkuk Min, Jung S Park, Yong-Kook Kang
Methylated-DNA sequencing technologies are producing vast amounts of methylome data from cancer samples, from which cancer-associated differentially methylated CpG sites (cDMCs) are continuously identified and filed. The inclusion of as many cDMCs as possible helps improve the accuracy of cancer diagnosis and sometimes identify cancer subtypes. However, the lack of an established method for the analysis of 100s of cDMCs practically impedes their robust use in clinical medicine. Here, we tested the availability of targeted bisulfite-PCR-sequencing (TBPseq) technology for the assessment of methylation levels of a myriad of CpGs scattered over the genome...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28748988/-characterization-of-patients-with-sporadic-colorectal-cancer-following-the-new-consensus-molecular-subtypes-cms
#2
Ana María Wielandt, Cynthia Villarroel, Claudia Hurtado, Daniela Simian, Diego Zamorano, Maripaz Martínez, Magdalena Castro, María Teresa Vial, Udo Kronberg, Francisco López-Kostner
BACKGROUND: Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor. AIM: To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways...
April 2017: Revista Médica de Chile
https://www.readbyqxmd.com/read/28748213/metabolic-reprogramming-underlies-metastatic-potential-in-an-obesity-responsive-murine-model-of-metastatic-triple-negative-breast-cancer
#3
Ciara H O'Flanagan, Emily L Rossi, Shannon B McDonell, Xuewen Chen, Yi-Hsuan Tsai, Joel S Parker, Jerry Usary, Charles M Perou, Stephen D Hursting
The vast majority of cancer-related deaths are due to metastatic disease, whereby primary tumor cells disseminate and colonize distal sites within the body. Triple negative breast cancer typically displays aberrant Wnt signaling, lacks effective targeted therapies, and compared with other breast cancer subtypes, is more likely to recur and metastasize. We developed a Wnt-driven lung metastasis model of triple negative breast cancer (metM-Wnt(lung)) through serial passaging of our previously described, nonmetastatic, claudin-low M-Wnt cell line...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28742689/lymphangiogenic-gene-expression-is-associated-with-lymph-node-recurrence-and-poor-prognosis-after-partial-hepatectomy-for-colorectal-liver-metastasis
#4
Thomas T Vellinga, Onno Kranenburg, Nicola Frenkel, Inge Ubink, Dieuwke Marvin, Klaas Govaert, Susanne van Schelven, Jeroen Hagendoorn, Inne H Borel Rinkes
OBJECTIVES: To investigate the relevance of lymphangiogenic gene expression in primary and liver metastasis of colorectal cancer (CRC) and identify determinants of lymphatic invasion. BACKGROUND: Lymphatic development promoting vascular endothelial growth factor C (VEGFC) is associated with poor outcome in primary CRC. For colorectal liver metastasis (CRLM), intrahepatic lymph invasion and lymph node metastasis are poor prognostic factors. Exact biological factors promoting lymphatic involvement remain elusive, just as the association with molecular subtypes of CRC...
July 24, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28739799/lgr5-receptor-promotes-cell-cell-adhesion-in-stem-cells-and-colon-cancer-cells-via-the-iqgap1-rac1-pathway
#5
Kendra S Carmon, Xing Gong, Jing Yi, Ling Wu, Anthony Thomas, Catherine M Moore, Ikuo Masuho, David J Timson, Kirill A Martemyanov, Qingyun J Liu
Leucine rich repeat containing G protein coupled receptor 5 (LGR5) is a bona fide marker of adult stem cells in several epithelial tissues, most notably in the intestinal crypts and is highly upregulated in many colorectal, hepatocellular, and ovarian cancers. LGR5 activation by R-spondin (RSPO) ligands potentiates Wnt/β-catenin signaling in vitro, yet deletion of LGR5 in stem cells has little or no effect on Wnt/β-catenin signaling or cell proliferation in vivo. Remarkably, modulation of LGR5 expression has a major impact on the actin cytoskeletal structure and cell adhesion in the absence of RSPO stimulation, but the molecular mechanism is unclear...
July 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28698102/neonatal-nav1-5-protein-expression-in-normal-adult-human-tissues-and-breast-cancer
#6
Rezan Fahrioglu Yamaci, Scott P Fraser, Esra Battaloglu, Handan Kaya, Kamil Erguler, Christopher S Foster, Mustafa B A Djamgoz
Expression of the neonatal splice variant of the voltage-gated sodium channel α-subunit (VGSC) subtype Nav1.5 (nNav1.5), encoded by the gene SCN5A, was shown earlier to be upregulated in human breast cancer (BCa), both in vitro and in vivo. Channel activity promoted BCa invasion of Matrigel(®)in vitro and metastasis in vivo. Consequently, expression of nNav1.5 has been proposed as a functional biomarker of BCa cells with metastatic potential. Here, we have determined immunohistochemically both nNav1.5 and total VGSC (tVGSC) protein expression in a range of adult human tissues...
August 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28692036/neoadjuvant-chemotherapy-affects-molecular-classification-of-colorectal-tumors
#7
K Trumpi, I Ubink, A Trinh, M Djafarihamedani, J M Jongen, K M Govaert, S G Elias, S R van Hooff, J P Medema, M M Lacle, L Vermeulen, I H M Borel Rinkes, O Kranenburg
The recent discovery of 'molecular subtypes' in human primary colorectal cancer has revealed correlations between subtype, propensity to metastasize and response to therapy. It is currently not known whether the molecular tumor subtype is maintained after distant spread. If this is the case, molecular subtyping of the primary tumor could guide subtype-targeted therapy of metastatic disease. In this study, we classified paired samples of primary colorectal carcinomas and their corresponding liver metastases (n=129) as epithelial-like or mesenchymal-like, using a recently developed immunohistochemistry-based classification tool...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28690657/epigenetic-silencing-of-mort-is-an-early-event-in-cancer-and-is-associated-with-luminal-receptor-positive-breast-tumor-subtypes
#8
Lukas Vrba, Bernard Walter Futscher
Immortality is an essential characteristic of cancer cells; a recent transcriptomic study of epithelial cell immortalization has linked epigenetic silencing of the long noncoding RNA Mortal Obligate RNA Transcript (MORT; alias ZNF667-AS1) to this process. This study evaluated the epigenetic and transcriptional state of MORT in two premalignant conditions-ductal carcinomas in situ and colon adenomas. Results show that MORT silencing is an early epigenetic event in human carcinogenesis, likely occurring near the point where premalignant cells gain immortality; this epigenetic silencing is maintained throughout malignant transformation and metastatic growth...
June 2017: Journal of Breast Cancer
https://www.readbyqxmd.com/read/28684753/line-1-hypomethylation-is-not-a-common-event-in-preneoplastic-stages-of-gastric-carcinogenesis
#9
Juozas Kupcinskas, Ruta Steponaitiene, Cosima Langner, Giedre Smailyte, Jurgita Skieceviciene, Limas Kupcinskas, Peter Malfertheiner, Alexander Link
LINE-1 hypomethylation is widely accepted as marker for global genomic DNA hypomethylation, which is a frequent event in cancer. The aim of the study was to evaluate LINE-1 methylation status at different stages of gastric carcinogenesis and evaluate its prognostic potential in clinical settings. LINE-1 methylation was analyzed in 267 tissue samples by bisulfite pyrosequencing including primary colorectal cancer tissues (T-CRC) with corresponding adjacent colon mucosa (N-CRC), gastric cancer tissues (T-GC) with corresponding gastric mucosa (N-GC), normal gastric tissues (N), chronic non-atrophic and atrophic gastritis (CG)...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28683746/multi-omics-of-34-colorectal-cancer-cell-lines-a-resource-for-biomedical-studies
#10
Kaja C G Berg, Peter W Eide, Ina A Eilertsen, Bjarne Johannessen, Jarle Bruun, Stine A Danielsen, Merete Bjørnslett, Leonardo A Meza-Zepeda, Mette Eknæs, Guro E Lind, Ola Myklebost, Rolf I Skotheim, Anita Sveen, Ragnhild A Lothe
BACKGROUND: Colorectal cancer (CRC) cell lines are widely used pre-clinical model systems. Comprehensive insights into their molecular characteristics may improve model selection for biomedical studies. METHODS: We have performed DNA, RNA and protein profiling of 34 cell lines, including (i) targeted deep sequencing (n = 612 genes) to detect single nucleotide variants and insertions/deletions; (ii) high resolution DNA copy number profiling; (iii) gene expression profiling at exon resolution; (iv) small RNA expression profiling by deep sequencing; and (v) protein expression analysis (n = 297 proteins) by reverse phase protein microarrays...
July 6, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28683472/comprehensive-analysis-of-copy-number-aberrations-in-microsatellite-stable-colon-cancer-in-view-of-stromal-component
#11
M Henar Alonso, Susanna Aussó, Adriana Lopez-Doriga, David Cordero, Elisabet Guinó, Xavier Solé, Mercè Barenys, Javier de Oca, Gabriel Capella, Ramón Salazar, Rebeca Sanz-Pamplona, Victor Moreno
BACKGROUND: Somatic copy number aberrations (CNAs) are common acquired changes in cancer cells having an important role in the progression of colon cancer (colorectal cancer, CRC). This study aimed to perform a characterisation of CNA and their impact in gene expression. METHODS: Copy number aberrations were inferred from SNP array data in a series of 99 CRC. Copy number aberration events were calculated and used to assess the association between copy number dosage, clinical and molecular characteristics of the tumours, and gene expression changes...
July 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28676564/calcium-intake-and-risk-of-colorectal-cancer-according-to-expression-status-of-calcium-sensing-receptor-casr
#12
Wanshui Yang, Li Liu, Yohei Masugi, Zhi Rong Qian, Reiko Nishihara, NaNa Keum, Kana Wu, Stephanie Smith-Warner, Yanan Ma, Jonathan A Nowak, Fatemeh Momen-Heravi, Libin Zhang, Michaela Bowden, Teppei Morikawa, Annacarolina da Silva, Molin Wang, Andrew T Chan, Charles S Fuchs, Jeffrey A Meyerhardt, Kimmie Ng, Edward Giovannucci, Shuji Ogino, Xuehong Zhang
OBJECTIVE: Although evidence suggests an inverse association between calcium intake and the risk of colorectal cancer, the mechanisms remain unclear. The calcium-sensing receptor (CASR) is expressed abundantly in normal colonic epithelium and may influence carcinogenesis. We hypothesized that calcium intake might be associated with lower risk of CASR-positive, but not CASR-negative, colorectal cancer. DESIGN: We assessed tumour CASR protein expression using immunohistochemistry in 779 incident colon and rectal cancer cases that developed among 136 249 individuals in the Nurses' Health Study and Health Professionals Follow-Up Study...
July 4, 2017: Gut
https://www.readbyqxmd.com/read/28674287/a-case-of-myasthenia-gravis-and-myositis-induced-by-nivolumab
#13
Fumie Konoeda, Shigeaki Suzuki, Yoshinori Nishimoto, Haruhiko Hoshino, Makoto Takagi
A 74-year-old woman, who developed advanced colon cancer with focal recurrence, received two courses of a low dose of nivolumab. Five days after the second course she noticed bilateral ptosis. Her symptoms rapidly progressed to generalized manifestations including limb and neck weakness, dyspnea, and myalgia within the following two weeks. Neurological and laboratory findings supported the diagnosis of myasthenia gravis and myositis induced by nivolumab. The combination immunotherapy including oral prednisolone, intravenous immunoglobulin and plasma exchange with noninvasive positive-pressure ventilation successfully avoid tracheal intubation...
June 30, 2017: Rinshō Shinkeigaku, Clinical Neurology
https://www.readbyqxmd.com/read/28660748/angiotensin-ii-subtype-1a-receptor-signaling-in-resident-hepatic-macrophages-induces-liver-metastasis-formation
#14
Yuki Shimizu, Hideki Amano, Yoshiya Ito, Tomohiro Betto, Sakiko Yamane, Tomoyoshi Inoue, Nobuyuki Nishizawa, Yoshio Matsui, Mariko Kamata, Masaki Nakamura, Hidero Kitasato, Wasaburo Koizumi, Masataka Majima
Liver metastases from colorectal cancer (CRC) are a clinically significant problem. The renin-angiotensin system (RAS) is involved in the tumor growth and metastases. This study was designed to evaluate the role of angiotensin II subtype receptor 1a (AT1a) in the formation of liver metastasis in CRC. A model of liver metastasis was made by intra-splenic injection of mouse colon cancer (CMT-93) into AT1a knockout mice (AT1aKO) and wild-type (C57BL/6) mice (WT). As compared with WT, the liver weight and liver metastatic rate were significantly lower in AT1aKO...
June 29, 2017: Cancer Science
https://www.readbyqxmd.com/read/28651562/grape-a-pathway-template-method-to-characterize-tissue-specific-functionality-from-gene-expression-profiles
#15
Michael I Klein, David F Stern, Hongyu Zhao
BACKGROUND: Personalizing treatment regimes based on gene expression profiles of individual tumors will facilitate management of cancer. Although many methods have been developed to identify pathways perturbed in tumors, the results are often not generalizable across independent datasets due to the presence of platform/batch effects. There is a need to develop methods that are robust to platform/batch effects and able to identify perturbed pathways in individual samples. RESULTS: We present Gene-Ranking Analysis of Pathway Expression (GRAPE) as a novel method to identify abnormal pathways in individual samples that is robust to platform/batch effects in gene expression profiles generated by multiple platforms...
June 26, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28646407/associations-of-red-and-processed-meat-intake-with-major-molecular-pathological-features-of-colorectal-cancer
#16
Prudence R Carr, Lina Jansen, Stefanie Bienert, Wilfried Roth, Esther Herpel, Matthias Kloor, Hendrik Bläker, Jenny Chang-Claude, Hermann Brenner, Michael Hoffmeister
Red and processed meat is an established risk factor for colorectal cancer (CRC). However, exact mechanisms to explain the associations remain unclear. Few studies have investigated the association with CRC by molecular tumor features, which could provide relevant information on associated molecular pathways. In this population-based case-control study from Germany (DACHS), 2449 cases and 2479 controls provided information on risk factors of CRC and completed a food frequency questionnaire. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between meat intake and risk of CRC by molecular pathologic features and specific subtypes...
May 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28607876/chromophobe-renal-cell-carcinoma-and-the-synchronous-presence-of-primary-colon-malignancies-is-there-a-relation
#17
Georgios Sahsamanis, Ilias Katikaridis, Georgios Mikros, Vasileios Tzelepis, Dionysios Pinialidis, Titos Deverakis, Georgios Dimitrakopoulos
While the presence of multiple primary malignancies in the same patient is a well described phenomenon, there is no clear association between various histological subtypes of renal cell carcinoma (RCC) and the synchronous presence of colon malignancies. We present the rare case of an 81-year-old female patient suffering from chromophobe renal cell carcinoma (chRCC) and an angiomyolipoma of her left kidney, synchronous with an adenocarcinoma of the caecum. While there is an established connection between RCC and colon cancer, a literature review is performed to specify this association in regard to chRCC and the synchronous presence of colon malignancies...
September 2017: Urology Case Reports
https://www.readbyqxmd.com/read/28570747/caspase14-expression-is-associated-with-triple-negative-phenotypes-and-cancer-stem-cell-marker-expression-in-breast-cancer-patients
#18
Tadashi Handa, Ayaka Katayama, Takehiko Yokobori, Arito Yamane, Jun Horiguchi, Reika Kawabata-Iwakawa, Susumu Rokudai, Pinjie Bao, Navchaa Gombodorj, Bolag Altan, Kyoichi Kaira, Takayuki Asao, Hiroyuki Kuwano, Masahiko Nishiyama, Tetsunari Oyama
BACKGROUND AND OBJECTIVES: The Caspase14 (CASP14) was reported that the low expression of CASP14 in ovarian cancer and colon cancer was associated with cancer progression, on the other hand, that the CASP14 expression in breast cancer was higher than that of non-cancerous tissues. The purpose of this study is to determine the clinical significance of CASP14 in breast cancer. METHODS: We performed immunohistochemistry for CASP14, ER, PgR, HER2, Ki67, EGFR, CK5/6, CD44, CD24, ALDH1, claudins, and androgen receptor in 222 breast cancer patients including 55 TNBC cases, and evaluated the relationship of CASP14, above-mentioned markers, and prognosis...
June 1, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28560691/role-of-tgf-%C3%AE-in-metastatic-colon-cancer-it-is-finally-time-for-targeted-therapy
#19
REVIEW
Maria Villalba, Stephanie R Evans, Fernando Vidal-Vanaclocha, Alfonso Calvo
Colorectal cancer (CRC) is one of the most frequent tumor types in Western countries. Approximately 20 % of patients show metastasis at the time of diagnosis, with the liver being one of the most affected organs. Transforming growth factor-beta (TGF-β) plays a regulatory role not only in the physiology of the normal colon but also in the development of CRC and its metastatic process. In this review, we analyze the molecular mechanisms leading to TGF-β dysregulation in tumor and stroma cells and the modification of the microenvironment that fosters CRC metastasis...
May 30, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28549410/large-scale-tissue-histopathology-image-classification-segmentation-and-visualization-via-deep-convolutional-activation-features
#20
Yan Xu, Zhipeng Jia, Liang-Bo Wang, Yuqing Ai, Fang Zhang, Maode Lai, Eric I-Chao Chang
BACKGROUND: Histopathology image analysis is a gold standard for cancer recognition and diagnosis. Automatic analysis of histopathology images can help pathologists diagnose tumor and cancer subtypes, alleviating the workload of pathologists. There are two basic types of tasks in digital histopathology image analysis: image classification and image segmentation. Typical problems with histopathology images that hamper automatic analysis include complex clinical representations, limited quantities of training images in a dataset, and the extremely large size of singular images (usually up to gigapixels)...
May 26, 2017: BMC Bioinformatics
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