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https://www.readbyqxmd.com/read/28505475/colorectal-cancer-subtypes-translation-to-routine-clinical-pathology
#1
REVIEW
Antonia K Roseweir, Donald C McMillan, Paul G Horgan, Joanne Edwards
Colorectal cancer (CRC) is the second most common cause of cancer death in Europe. Although outcomes have improved, it is clear that from a genomic standpoint CRC is not one disease, but a heterogeneous group of malignancies that arise within one organ. Given that different subtypes have different outcomes, the ability to subtype tumours in the clinic would be highly favourable, enabling optimal treatment for individual patients. In 2015, a consortium proposed four consensus subtypes for CRC (MSI immune, canonical, metabolic, and mesenchymal) based on six classifications systems reported to have prognostic value...
May 4, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28494874/molecular-subtype-specific-biomarkers-improve-prediction-of-prognosis-in-colorectal-cancer
#2
Jesper Bertram Bramsen, Mads Heilskov Rasmussen, Halit Ongen, Trine Block Mattesen, Mai-Britt Worm Ørntoft, Sigrid Salling Árnadóttir, Juan Sandoval, Teresa Laguna, Søren Vang, Bodil Øster, Philippe Lamy, Mogens Rørbæk Madsen, Søren Laurberg, Manel Esteller, Emmanouil Theophilos Dermitzakis, Torben Falck Ørntoft, Claus Lindbjerg Andersen
Colorectal cancer (CRC) is characterized by major inter-tumor diversity that complicates the prediction of disease and treatment outcomes. Recent efforts help resolve this by sub-classification of CRC into natural molecular subtypes; however, this strategy is not yet able to provide clinicians with improved tools for decision making. We here present an extended framework for CRC stratification that specifically aims to improve patient prognostication. Using transcriptional profiles from 1,100 CRCs, including >300 previously unpublished samples, we identify cancer cell and tumor archetypes and suggest the tumor microenvironment as a major prognostic determinant that can be influenced by the microbiome...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28486044/non-v600-braf-mutations-define-a-clinically-distinct-molecular-subtype-of-metastatic-colorectal-cancer
#3
Jeremy C Jones, Lindsay A Renfro, Humaid O Al-Shamsi, Alexa B Schrock, Andrew Rankin, Ben Y Zhang, Pashtoon M Kasi, Jesse S Voss, Alexis D Leal, James Sun, Jeffrey Ross, Siraj M Ali, Joleen M Hubbard, Benjamin R Kipp, Robert R McWilliams, Scott Kopetz, Robert A Wolff, Axel Grothey
Purpose Molecular diagnostic testing has become an integral part of the evaluation of patients with metastatic colorectal cancer (CRC). Expanded mutational testing, such as next-generation sequencing (NGS), often identifies mutations with unclear clinical or prognostic implications. One such example is BRAF mutations that occur outside of codon 600 ((non-V600) BRAF mutations). Methods We conducted this multicenter, retrospective cohort study to characterize the clinical, pathologic, and survival implications of (non-V600) BRAF mutations in metastatic CRC...
May 9, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28475173/microrna-30a-attenuates-mutant-kras-driven-colorectal-tumorigenesis-via-direct-suppression-of-me1
#4
Hongxing Shen, Chuan Xing, Kaisa Cui, Yunxiao Li, Jinxiang Zhang, Runlei Du, Xiaodong Zhang, Youjun Li
Frequent KRAS mutations contribute to multiple cancers including ~40% of human colorectal cancers (CRCs). Systematic screening of 1255 microRNAs (miRNAs) identified miR-30a as a synthetic lethal in KRAS-mutant CRC cells. miR-30a was downregulated in CRCs and repressed by P65. miR-30a directly targeted malic enzyme 1 (ME1) and KRAS, and inhibited anchorage-independent growth and in vivo tumorigenesis by KRAS-mutant CRC cells. ME1 was significantly upregulated in KRAS-mutant CRCs. Eliminating ME1 by short hairpin RNA (shRNA) resulted in obviously decreased NADPH production, levels of triglyceride and fatty acid, and an inhibition of tumorigenicity of KRAS-mutant CRCs...
May 5, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28468569/colorectal-cancer-in-patients-under-the-age-of-40-years-experience-from-a-tertiary-care-centre-in-the-czech-republic
#5
Petr Kocián, Adam Whitley, Milan Blaha, Jiří Hoch
INTRODUCTION: Colorectal cancer (CRC) in young patients is not an uncommon disease. Reports on its behaviour in young patients are conflicting. The aim of this study was to investigate patient and tumour characteristics, treatment and prognosis of this disease. METHODS: Our study group comprised all patients under the age of 40 years treated with CRC at the Department of Surgery at Motol University Hospital in Prague between the years 2005 and 2015. RESULTS: Thirty-eight patients under 40 years of age diagnosed with CRC were included in the study...
May 4, 2017: Acta Chirurgica Belgica
https://www.readbyqxmd.com/read/28455965/prognosis-of-stage-iii-colorectal-carcinomas-with-folfox-adjuvant-chemotherapy-can-be-predicted-by-molecular-subtype
#6
Yujin Kwon, Minhee Park, Mi Jang, Seongju Yun, Won Kyu Kim, Sora Kim, Soonmyung Paik, Hyun Jung Lee, Sungpil Hong, Tae Il Kim, Byungsoh Min, Hoguen Kim
Individualizing adjuvant chemotherapy is important in patients with advanced colorectal cancers (CRCs), and the ability to identify molecular subtypes predictive of good prognosis for stage III CRCs after adjuvant chemotherapy could be highly beneficial. We performed microarray-based gene expression analysis on 101 fresh-frozen primary samples from patients with stage III CRCs treated with FOLFOX adjuvant chemotherapy and 35 matched non-neoplastic mucosal tissues. CRC samples were classified into four molecular subtypes using nonnegative matrix factorization, and for comparison, we also grouped CRC samples using the proposed consensus molecular subtypes (CMSs)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424049/findings-in-young-adults-at-colonoscopy-from-a-hospital-service-database-audit
#7
Stephanie Wong, Ilmars Lidums, Christophe Rosty, Andrew Ruszkiewicz, Susan Parry, Aung Ko Win, Yoko Tomita, Sina Vatandoust, Amanda Townsend, Dainik Patel, Jennifer E Hardingham, David Roder, Eric Smith, Paul Drew, Julie Marker, Wendy Uylaki, Peter Hewett, Daniel L Worthley, Erin Symonds, Graeme P Young, Timothy J Price, Joanne P Young
BACKGROUND: Colorectal cancer (CRC) diagnosed at <50 years is predominantly located in the distal colon and rectum. Little is known about which lesion subtypes may serve as CRC precursors in young adults. The aim of this work was to document the prevalence and histological subtype of lesions seen in patients aged <50 years, and any associated clinical features. METHODS: An audit of the colonoscopy database at The Queen Elizabeth Hospital in Adelaide, South Australia over a 12-month period was undertaken...
April 19, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28418874/is-there-a-prognostic-value-of-tumor-location-among-chinese-patients-with-colorectal-cancer
#8
Fangqi Liu, Cong Li, Huixun Jia, Li Yang, Yuchen Wu, Jiang Zhao, Sanjun Cai, Ji Zhu, Ye Xu
Differences in epidemiology, pathological features, and molecular pathogeneses have been observed according to primary tumor location in colorectal cancer (CRC). However, predicting CRC survival by tumor location remains controversial. Therefore, we compared the pathological characteristics, molecular features, and prognoses of right-side colon cancer (RCC), left-side colon cancer (LCC), and rectal cancer (RECC) among Chinese patients with CRC. We evaluated 4,426 patients with stage I-III CRC between January 2008 and July 2014from Fudan University Shanghai Cancer Center...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416736/nomo-1-gene-is-deleted-in-early-onset-colorectal-cancer
#9
José Perea, Juan Luis García, Jessica Pérez, Daniel Rueda, María Arriba, Yolanda Rodríguez, Miguel Urioste, Rogelio González-Sarmiento
To characterize clinical features of a recurrent alteration in 16p13.12-p13.11 in Colorectal Cancer (CRC), mainly in Early-onset subgroup (EOCRC), and to assess the status of NOMO1, a gene located in that region, we analyzed differential clinicopathological, familial and molecular features of CRC subsets with and without alterations in the 16p13.12-p13.11, in global and EOCRC groups. We confirmed the region by fluorescence in-situ hybridization, and Quantitative Real-Time PCR analyzed the status of NOMO1 in different age-of-onset and Microsatellite Instability (MSI)-status CRC subsets...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413436/predominance-and-association-risk-of-blastocystis-hominis-subtype-i-in-colorectal-cancer-a-case-control-study
#10
Amr Mohamed Mohamed, Mona Abdelfattah Ahmed, Sabah Abdelghany Ahmed, Sherif Ahmed Al-Semany, Saad Saed Alghamdi, Dina Abdulla Zaglool
BACKGROUND: Blastocystis, a genetically diverse intestinal parasite with controversial pathogenic potential, has increasingly been incriminated for diarrheal illness in immunocompromised individuals including colorectal cancer (CRC) patients. The aim of the current study was to assess the possible association between Blastocystis infection and CRC condition in Makkah, Saudi Arabia (KSA). METHODS: Stool samples were collected from 80 non-cancer (NC) and 138 cancer subjects including 74 CRC patients and 64 patients with other cancers outside gastrointestinal tract (COGT)...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28408791/all-trans-retinoic-acid-modulates-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway-targeting-tnf-%C3%AE-and-nitric-oxide-synthase-2-expression-in-colonic-mucosa-during-ulcerative-colitis-and-colitis-associated-cancer
#11
Hayet Rafa, Sarra Benkhelifa, Sonia AitYounes, Houria Saoula, Said Belhadef, Mourad Belkhelfa, Aziza Boukercha, Ryma Toumi, Imene Soufli, Olivier Moralès, Yvan de Launoit, Hassen Mahfouf, M'hamed Nakmouche, Nadira Delhem, Chafia Touil-Boukoffa
Colitis associated cancer (CAC) is the colorectal cancer (CRC) subtype that is associated with bowel disease such as ulcerative colitis (UC). The data on role of NF-κB signaling in development and progression of CAC were derived from preclinical studies, whereas data from human are rare. The aim of this work was to study the contribution of NF-κB pathway during UC and CAC, as well as the immunomodulatory effect of all-trans retinoic acid (AtRA). We analyzed the expression of NOS2, TNF-α, TLR4, and NF-κB, in colonic mucosa...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28378457/dna-methylation-epigenotype-and-clinical-features-of-nras-mutation-colorectal-cancer
#12
Kiyoko Takane, Kiwamu Akagi, Masaki Fukuyo, Koichi Yagi, Tadatoshi Takayama, Atsushi Kaneda
Sporadic colorectal cancer (CRC) is classified into several molecular subtypes. We previously established two groups of DNA methylation markers through genome-wide DNA methylation analysis to classify CRC into distinct subgroups: high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME, respectively). HME CRC, also called CpG island methylator phenotype (CIMP)-high CRC, shows methylation of both Group 1 markers (CIMP markers) and Group 2 markers, while IME/CIMP-low CRC shows methylation of Group 2, but not of Group 1 markers, and LME CRC shows no methylation of either Group 1 or Group 2 markers...
May 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28351398/genome-wide-methylation-analysis-identifies-a-core-set-of-hypermethylated-genes-in-cimp-h-colorectal-cancer
#13
Tyler McInnes, Donghui Zou, Dasari S Rao, Francesca M Munro, Vicky L Phillips, John L McCall, Michael A Black, Anthony E Reeve, Parry J Guilford
BACKGROUND: Aberrant DNA methylation profiles are a characteristic of all known cancer types, epitomized by the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). Hypermethylation has been observed at CpG islands throughout the genome, but it is unclear which factors determine whether an individual island becomes methylated in cancer. METHODS: DNA methylation in CRC was analysed using the Illumina HumanMethylation450K array. Differentially methylated loci were identified using Significance Analysis of Microarrays (SAM) and the Wilcoxon Signed Rank (WSR) test...
March 28, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28326211/early-onset-signet-ring-cell-adenocarcinoma-of-the-colon-a-case-report-and-review-of-the-literature
#14
Maliha Khan, Krittiya Korphaisarn, Aneeqa Saif, Wai C Foo, Scott Kopetz
Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths in the United States. While a decline has been observed in the older population, the occurrence of CRC in the adolescent and young adult (AYA) population has increased over the past two decades. The histopathologic characteristics and clinical behavior of CRC in AYA patients have been shown to be distinct from those of CRC in older adults. The rarer subtypes of CRC such as mucinous adenocarcinoma and signet-ring cell carcinoma are associated with a poorer prognosis compared to the more common subtypes...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28299802/bmp-and-notch-interaction-in-crc-subtypes
#15
Shazia Irshad, Mukesh Bansal, Paolo Guarnieri, Hayley Davis, Ayman Al Haj Zen, Brygida Baran, Claudia Maria Assunta Pinna, Haseeb Rahman, Sujata Biswas, Chiara Bardella, Rosemary Jeffery, Lai Mun Wang, James Edward East, Annabelle Lewis, Ian Tomlinson, Simon John Leedham
The functional role of Bone Morphogenetic Protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes...
March 15, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28293308/mismatch-repair-proteins-and-microsatellite-instability-in-colorectal-carcinoma-mlh1-msh2-msh6-and-pms2-histopathological-and-immunohistochemical-study
#16
Nour El Hoda S Ismael, Samar A El Sheikh, Suzan M Talaat, Eman M Salem
BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Microsatellite instability (MSI) is detected in about 15% of all colorectal cancers. CRC with MSI has particular characteristics such as improved survival rates and better prognosis. They also have a distinct sensitivity to the action of chemotherapy. AIM: The aim of the study was to detect microsatellite instability in a cohort of colorectal cancer Egyptian patients using the immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2)...
March 15, 2017: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28289479/colorectal-adenoma-and-carcinoma-specific-mirna-profiles-in-biopsy-and-their-expression-in-plasma-specimens
#17
Zsófia Brigitta Nagy, Barnabás Wichmann, Alexandra Kalmár, Orsolya Galamb, Barbara Kinga Barták, Sándor Spisák, Zsolt Tulassay, Béla Molnár
BACKGROUND: MiRNA expression markers are well characterized in colorectal cancer (CRC), but less is known about miRNA expression profiles in colorectal adenomas. Genome-wide miRNA and mRNA expression analyses were conducted through the colorectal adenoma dysplasia sequence. Furthermore, analysis of the expression levels of miRNAs in matched plasma samples was performed, focusing on biomarker candidates; miRNA and mRNA expression analyses were performed on colorectal biopsies and plasma samples (20 normals; 11 tubular and 9 tubulovillous adenomas; 20 colorectal carcinomas) by miRNA 3...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28280610/investigation-of-the-human-h3-3b-h3f3b-gene-expression-as-a-novel-marker-in-patients-with-colorectal-cancer
#18
Habib Allah Ayoubi, Frouzandeh Mahjoubi, Rezvan Mirzaei
BACKGROUND: H3.3 histone is a replacement histone subtype that is express in entire cell cycle phases and overexpress in transcriptionally active regions, promoter regions, and intergenic or intragenic regulatory elements. This histone encoded by two genes termed H3.3A (H3F3A) and H3.3B (H3F3B). Mutations of these two genes lead to some human cancers such as chondroblastoma, osteosarcoma, and epithelial ovarian cancer. The aims of this study were to quantitatively examine the expression of H3...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28278514/distinct-clinical-outcomes-of-two-cimp-positive-colorectal-cancer-subtypes-based-on-a-revised-cimp-classification-system
#19
Jeong Mo Bae, Jung Ho Kim, Yoonjin Kwak, Dae-Won Lee, Yongjun Cha, Xianyu Wen, Tae Hun Lee, Nam-Yun Cho, Seung-Yong Jeong, Kyu Joo Park, Sae Won Han, Hye Seung Lee, Tae-You Kim, Gyeong Hoon Kang
BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease in terms of molecular carcinogenic pathways. Based on recent findings regarding the multiple serrated neoplasia pathway, we revised an eight-marker panel for a new CIMP classification system. METHODS: 1370 patients who received surgical resection for CRCs were classified into three CIMP subtypes (CIMP-N: 0-4 methylated markers, CIMP-P1: 5-6 methylated markers and CIMP-P2: 7-8 methylated markers). Our findings were validated in a separate set of high-risk stage II or stage III CRCs receiving adjuvant fluoropyrimidine plus oxaliplatin (n=950)...
April 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28277887/rnai-high-throughput-screening-of-single-and-multi-cell-type-tumor-spheroids-a-comprehensive-analysis-in-two-and-three-dimensions
#20
Jiaqi Fu, Daniel Fernandez, Marc Ferrer, Steven A Titus, Eugen Buehler, Madhu A Lal-Nag
The widespread use of two-dimensional (2D) monolayer cultures for high-throughput screening (HTS) to identify targets in drug discovery has led to attrition in the number of drug targets being validated. Solid tumors are complex, aberrantly growing microenvironments that harness structural components from stroma, nutrients fed through vasculature, and immunosuppressive factors. Increasing evidence of stromally-derived signaling broadens the complexity of our understanding of the tumor microenvironment while stressing the importance of developing better models that reflect these interactions...
June 2017: SLAS Discovery
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