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https://www.readbyqxmd.com/read/28794806/recent-developments-in-the-treatment-of-metastatic-colorectal-cancer
#1
REVIEW
Jonathan M Loree, Scott Kopetz
Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS/tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28774167/geographic-distribution-of-the-incidence-of-colorectal-cancer-in-iran-a-population-based-study
#2
Fatemeh Khosravi Shadmani, Erfan Ayubi, Salman Khazaei, Mohadeseh Sani, Shiva Mansouri Hanis, Somayeh Khazaei, Mokhtar Soheylizad, Kamyar Mansori
OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer death in the world. The aim of this study was to investigate the provincial distribution of the incidence of CRC across Iran. METHODS: This epidemiologic study used data from the National Cancer Registry of Iran and the Center for Disease Control and Prevention of the Ministry of Health and Medical Education of Iran. The average annual age-standardized rate (ASR) for the incidence of CRC was calculated for each province...
2017: Epidemiology and Health
https://www.readbyqxmd.com/read/28748988/-characterization-of-patients-with-sporadic-colorectal-cancer-following-the-new-consensus-molecular-subtypes-cms
#3
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/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/28741479/colorectal-cancer-subtypes-developmental-origin-and-microenvironmental-regulation
#5
REVIEW
Evelyn Fessler, Jan Paul Medema
Cancer is a heterogeneous disease and many cancer types do not represent a single entity, but are composed of biologically and clinically diverse subtypes. The subtype affiliation can influence prognosis and response to therapy. Recently, a multicenter colorectal cancer (CRC) subtyping consortium introduced a consensus molecular classification system for CRC. This will be of great benefit for future basic and clinical research since it enables uniform categorization of CRC specimens across different institutes and studies...
September 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28736626/molecular-landscape-and-sub-classification-of-gastrointestinal-cancers-a-review-of-literature
#6
REVIEW
Bita Fakhri, Kian-Huat Lim
The historical approach of diagnosing cancer types based entirely on anatomic origin and histologic features, and the "one-size-fit-all" therapeutic approach, are inadequate in modern cancer treatment. From decades of research we now know that cancer is a highly heterogeneous disease driven by complex genetic or epigenetic alterations. The advent of various high throughput molecular tools has now enabled us to view and sub-classify each cancer type based on their distinct molecular features, in addition to histologic classification, with the promise of individualized treatment strategies tailored towards each specific subtype to improve patient outcomes...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28730335/clinical-and-prognosis-value-of-the-cimp-status-combined-with-mlh1-or-p16-ink4a-methylation-in-colorectal-cancer
#7
Amana Saadallah-Kallel, Rania Abdelmaksoud-Dammak, Mouna Triki, Slim Charfi, Abdelmajid Khabir, Tahia Sallemi-Boudawara, Raja Mokdad-Gargouri
Aberrant DNA methylation of CpG islands occurred frequently in CRC and associated with transcriptional silencing of key genes. In this study, the CIMP combined with MLH1 or p16 (INK4a) methylation status was determined in CRC patients and correlated with clinicopathological parameters and overall survival. Our data showed that CIMP+ CRCs were identified in 32.9% of cases and that CACNAG1 is the most frequently methylated promoter. When we combined the CIMP with the MLH1 or the p16 (INK4a) methylation status, we found that CIMP-/MLH1-U (37...
August 2017: Medical Oncology
https://www.readbyqxmd.com/read/28718430/liquid-biopsies-in-colorectal-cancer-monitoring-genetic-heterogeneity
#8
Antonios N Gargalionis, Athanasios G Papavassiliou
Dynamic changes in the colorectal cancer (CRC) signalome and tumor genetic heterogeneity underlie acquired drug resistance. Improving treatment-related decisions is facilitated by an emerging consensus in the classification of tumor subtypes as well as by real-time monitoring of predictive biomarkers in circulating tumor cells and DNA.
March 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28687729/spectral-clustering-using-nystr%C3%A3-m-approximation-for-the-accurate-identification-of-cancer-molecular-subtypes
#9
Mingguang Shi, Guofu Xu
A major challenge in clinical cancer research is the identification of accurate molecular subtype. While unsupervised clustering methods have been applied for class discovery, this clustering method remains a bottleneck in developing accurate method for molecular subtype discovery. In this analysis, we hypothesize that spectral clustering method could identify molecular subtypes in correlation with survival outcomes. We propose an accurate subtype identification method, Cancer Subtype Identification with Spectral Clustering using Nyström approximation (CSISCN), for the discovery of molecular subtypes, based on spectral clustering method...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28686076/therapeutic-implications-of-bioactive-sphingolipids-a-focus-on-colorectal-cancer
#10
E Ramsay Camp, Logan D Patterson, Mark Kester, Christina Voelkel-Johnson
Therapy of colorectal cancer (CRC), especially a subset known as locally advanced rectal cancer, is challenged by progression and recurrence. Sphingolipids, a lipid subtype with vital roles in cellular function, play an important role in CRC and impact on therapeutic outcomes. In this review we discuss how dietary sphingolipids or the gut microbiome via alterations in sphingolipids influence CRC carcinogenesis. In addition, we discuss the expression of sphingolipid enzymes in the gastro-intestinal tract, their alterations in CRC, and the implications for therapy responsiveness...
July 7, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28684753/line-1-hypomethylation-is-not-a-common-event-in-preneoplastic-stages-of-gastric-carcinogenesis
#11
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
#12
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
#13
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/28681242/the-potential-role-of-platelets-in-the-consensus-molecular-subtypes-of-colorectal-cancer
#14
REVIEW
Michael Lam, Jason Roszik, Preeti Kanikarla-Marie, Jennifer S Davis, Jeffrey Morris, Scott Kopetz, David G Menter
The consensus molecular subtypes (CMS) in colorectal cancer (CRC) represent distinct molecular subcategories of disease as reflected by comprehensive molecular profiling. The four CMS subtypes represent unique biology. CMS1 represents high immune infiltration. CMS2 demonstrates upregulation of canonical pathways such as WNT signaling. Widespread metabolic changes are seen in CMS3. CMS4 represents a mesenchymal phenotype with hallmark features including complement activation, matrix remodeling, angiogenesis, epithelial-mesechymal transition (EMT), integrin upregulation and stromal infiltration...
July 6, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28660748/angiotensin-ii-subtype-1a-receptor-signaling-in-resident-hepatic-macrophages-induces-liver-metastasis-formation
#15
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/28659146/antibody-targeting-of-claudin-1-as-a-potential-colorectal-cancer-therapy
#16
S Cherradi, A Ayrolles-Torro, N Vezzo-Vié, N Gueguinou, V Denis, E Combes, F Boissière, M Busson, L Canterel-Thouennon, C Mollevi, M Pugnière, F Bibeau, M Ychou, P Martineau, C Gongora, M Del Rio
BACKGROUND: Metastatic colorectal cancer (mCRC) is one of the major causes of cancer-related death. Despite the substantial progress in mCRC management, it remains important to identify new therapeutic options and biological markers for personalized medicine. Here, we investigated the expression of claudin-1 (CLDN1), a major tight junction transmembrane protein, in the different colorectal cancer (CRC) molecular subtypes and then assessed the anti-tumor effect of a new anti-CLDN1 monoclonal antibody (mAb)...
June 28, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28646407/associations-of-red-and-processed-meat-intake-with-major-molecular-pathological-features-of-colorectal-cancer
#17
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/28625833/colorectal-cancer-cell-line-proteomes-are-representative-of-primary-tumors-and-predict-drug-sensitivity
#18
Jing Wang, Dmitri Mouradov, Xiaojing Wang, Robert N Jorissen, Matthew C Chambers, Lisa J Zimmerman, Suhas Vasaikar, Christopher G Love, Shan Li, Kym Lowes, Karl-Johan Leuchowius, Helene Jousset, Janet Weinstock, Christopher Yau, John Mariadason, Zhiao Shi, Yuguan Ban, Xi Chen, Robert J C Coffey, Robbert J C Slebos, Antony W Burgess, Daniel C Liebler, Bing Zhang, Oliver M Sieber
BACKGROUND AND AIMS: Proteomics holds promise for individualizing cancer treatment. We analyzed to what extent the proteomic landscape of human colorectal cancer (CRC) is maintained in established CRC cell lines and the utility of proteomics for predicting therapeutic responses. METHODS: Proteomic and transcriptomic analyses were performed on 44 CRC cell lines, compared against primary CRCs (n=95) and normal tissues (n=60), and integrated with genomic and drug sensitivity data...
June 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28625649/investigation-of-patterns-of-nodal-metastases-in-braf-mutant-lung-cancer
#19
S H McEvoy, D F Halpenny, A Viteri-Jusué, S A Hayes, A J Plodkowski, G J Riely, M S Ginsberg
Axillary lymph nodes (axLN) are a rare site of nodal metastases in patients with lung cancer. BRAF mutated lung cancer is a genetically distinct subtype that occurs in 2-5% of non-small cell lung carcinomas (NSCLC). A recent study identified a highly unusual pattern of metastatic spread to axLN in patients with BRAF mutated colorectal cancer (CRC). The purpose of the study is to assess the incidence of axLN metastases in BRAF mutated NSCLC. Baseline computed tomography (CT) imaging at diagnosis and all follow up CTs of patients with BRAF mutated NSCLC treated at our institution were retrospectively reviewed by two radiologists for evidence of axLN metastases...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28618397/meta-analysis-of-the-mutational-status-of-circulation-tumor-cells-and-paired-primary-tumor-tissues-from-colorectal-cancer-patients
#20
Yong Liu, Stefano Meucci, Liming Sheng, Ulrich Keilholz
As predictive markers for anti-EGFR therapy, KRAS and BRAF mutations are routinely detected in primary and metastatic colorectal cancer (CRC) cells, but seldom in circulating tumor cells (CTCs). Detecting mutations in CTCs could help explain mutational differences between tumor cells at local sites and distant metastases, thereby improving treatment outcomes. Here, we conducted a systematic review and meta-analysis to compare KRAS and BRAF mutations in paired CTCs and primary tumors from CRC patients, to detect any possible discordance...
May 26, 2017: Oncotarget
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