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https://www.readbyqxmd.com/read/27929064/acquired-ras-or-egfr-mutations-and-duration-of-response-to-egfr-blockade-in-colorectal-cancer
#1
Beth O Van Emburgh, Sabrina Arena, Giulia Siravegna, Luca Lazzari, Giovanni Crisafulli, Giorgio Corti, Benedetta Mussolin, Federica Baldi, Michela Buscarino, Alice Bartolini, Emanuele Valtorta, Joana Vidal, Beatriz Bellosillo, Giovanni Germano, Filippo Pietrantonio, Agostino Ponzetti, Joan Albanell, Salvatore Siena, Andrea Sartore-Bianchi, Federica Di Nicolantonio, Clara Montagut, Alberto Bardelli
Blockade of the epidermal growth factor receptor (EGFR) with the monoclonal antibodies cetuximab or panitumumab is effective in a subset of colorectal cancers (CRCs), but the emergence of resistance limits the efficacy of these therapeutic agents. At relapse, the majority of patients develop RAS mutations, while a subset acquires EGFR extracellular domain (ECD) mutations. Here we find that patients who experience greater and longer responses to EGFR blockade preferentially develop EGFR ECD mutations, while RAS mutations emerge more frequently in patients with smaller tumour shrinkage and shorter progression-free survival...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27922044/from-tumour-heterogeneity-to-advances-in-precision-treatment-of-colorectal-cancer
#2
REVIEW
Cornelis J A Punt, Miriam Koopman, Louis Vermeulen
In recent years, the high heterogeneity of colorectal cancer (CRC) has become evident. Hence, biomarkers need to be developed that enable the stratification of patients with CRC into different prognostic subgroups and in relation to response to therapies, according to the distinctive tumour biology. Currently, only RAS-mutation status is used routinely as a negative predictive marker to avoid treatment with anti-EGFR agents in patients with metastatic CRC, and mismatch-repair status can guide the use of adjuvant chemotherapy in patients with early stage colon cancer...
December 6, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27919977/microrna-7-is-associated-with-malignant-potential-and-poor-prognosis-in-human-colorectal-cancer
#3
Yuka Nagano, Yuji Toiyama, Yoshinaga Okugawa, Hiroki Imaoka, Hiroyuki Fujikawa, Hiromi Yasuda, Shigeyuki Yoshiyama, Junichiro Hiro, Minako Kobayashi, Masaki Ohi, Toshimitsu Araki, Yasuhiro Inoue, Yasuhiko Mohri, Masato Kusunoki
Dysregulation pattern of microRNA-7 (miR-7) and the clinical significance of its expression in colorectal cancer (CRC) are unresolved. Here, we investigated the relationship between clinicopathological factors, including prognostic outcome, and miR-7 expression in CRC tissues. We analyzed miR-7 expression levels by real-time reverse transcription polymerase chain reaction in 210 colorectal tissues (196 CRCs and 14 normal mucosae from healthy volunteers). miR-7 expression levels were significantly up-regulated in CRC tissues compared to normal colorectal mucosae...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919208/is-metformin-a-therapeutic-paradigm-for-colorectal-cancer-insight-into-the-molecular-pathway
#4
Zar Chii Thent, Nurul Hannim Zaidun, Fairuz Azmi, Mu Izuddin Senin, Haszianaliza Haslan, Ahmad Ruzain Salehuddin
Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the absence of diabetes mellitus...
December 5, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27914767/smad-4-gene-expression-in-human-colorectal-cancer-comparison-with-some-clinical-and-pathological-parameters
#5
Agnieszka Wosiak, Damian Wodziński, Marcin Kolasa, Aleksandra Sałagacka-Kubiak, Ewa Balcerczak
The aim of this study was to evaluate the expression of SMAD-4 gene in cases of colorectal cancer and to link the obtained data with the development of this disease. SMAD-4 gene is responsible for the control of many important cellular processes, for example prevention of excessive epithelial cell growth and divisions. This suppressor gene is located on chromosome 18 within the region with frequent genetic losses in colorectal cancer. Inactivation of this gene is commonly found in pancreatic cancer where the SMAD-4 gene lost in the expression has been associated with a poor prognosis in this cancer...
October 26, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27914515/measurement-of-red-blood-cell-eicosapentaenoic-acid-epa-levels-in-a-randomised-trial-of-epa-in-patients-with-colorectal-cancer-liver-metastases
#6
Henry Watson, Andrew J Cockbain, Jade Spencer, Amanda Race, Milene Volpato, Paul M Loadman, Giles J Toogood, Mark A Hull
We investigated red blood cell (RBC) PUFA profiles, and the predictive value of RBC EPA content for tumour EPA exposure and clinical outcomes, in the EMT study, a randomised trial of EPA in patients awaiting colorectal cancer (CRC) liver metastasis surgery (Cockbain et al., 2014) [8]. There was a significant increase in RBC EPA in the EPA group (n=43; median intervention 30 days; mean absolute 1.26[±0.14]% increase; P<0.001), but not in the placebo arm (n=45). EPA incorporation varied widely in EPA users and was not explained by treatment duration or compliance...
December 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/27910284/resting-heart-rate-is-an-independent-predictor-of-death-in-patients-with-colorectal-pancreatic-and-non-small-cell-lung-cancer-results-of-a-prospective-cardiovascular-long-term-study
#7
Markus S Anker, Nicole Ebner, Bert Hildebrandt, Jochen Springer, Marianne Sinn, Hanno Riess, Stefan D Anker, Ulf Landmesser, Wilhelm Haverkamp, Stephan von Haehling
AIMS: Patients with advanced cancer have been shown to suffer from abnormal cardiac function and impaired exercise capacity that may contribute to their impaired quality of life. As tachycardia is considered as a sign of potential early cardiac damage, we sought to determine whether resting heart rate and other ECG-derived variables have prognostic value. METHODS AND RESULTS: From 2005 to 2010, we enrolled 145 patients with histologically confirmed cancer (36 colorectal, 72 pancreatic, and 37 non-small cell lung cancer patients) and 59 healthy controls...
December 2016: European Journal of Heart Failure
https://www.readbyqxmd.com/read/27907910/a-mononucleotide-repeat-in-prrt2-is-an-important-frequent-target-of-mismatch-repair-deficiency-in-cancer
#8
Inês Teles Alves, David Cano, René Böttcher, Hetty van der Korput, Winand Dinjens, Guido Jenster, Jan Trapman
The DNA mismatch repair (MMR) system corrects DNA replication mismatches thereby contributing to the maintenance of genomic stability. MMR deficiency has been observed in prostate cancer but its impact on the genomic landscape of these tumours is not known. In order to identify MMR associated mutations in prostate cancer we have performed whole genome sequencing of the MMR deficient PC346C prostate cancer cell line. We detected a total of 1196 mutations in PC346C which was 1.5-fold higher compared to a MMR proficient prostate cancer sample (G089)...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27907852/the-relevance-of-primary-tumour-location-in-patients-with-metastatic-colorectal-cancer-a-meta-analysis-of-first-line-clinical-trials
#9
Julian Walter Holch, Ingrid Ricard, Sebastian Stintzing, Dominik Paul Modest, Volker Heinemann
BACKGROUND: Retrospective subgroup analyses suggest that primary tumour location (PTL) has a prognostic importance and relates to response to targeted therapy. METHODS: We conducted a meta-analysis of first-line clinical trials available up to October 2016, which assessed the relevance of PTL in patients with metastatic colorectal cancer (mCRC). Right- and left-sided colorectal cancers were differentiated (RC and LC). RESULTS: In 13 first-line randomised controlled trials and one prospective pharmacogenetic study, RC was associated with a significantly worse prognosis compared with LC (hazard ratio [HR] for overall survival: 1...
November 29, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27899972/efficacy-and-safety-of-aflibercept-in-metastatic-colorectal-cancer-pretreated-with-bevacizumab-a-report-of-five-cases
#10
Julia Alcaide, Mayte Delgado, Marta Legerén, José Miguel Jurado, Isabel Blancas, Teresa Pereda, Jorge López, Margarita Garrido, María J Sánchez, José L García, Antonio Rueda
Aflibercept is a recombinant fusion protein that acts by inhibiting tumoural angiogenesis. Efficacy data obtained in the VELOUR randomised study has contributed to the approval of aflibercept as a second-line metastatic colorectal cancer (mCRC) treatment following an oxaliplatin-based regimen. The present study reports a case series of five patients with mCRC, who were treated in two centres since 2011 in the Compassionate Use Program for aflibercept. All patients had a KRAS mutation and previously received palliative fluoropyrimidine-oxaliplatin-based chemotherapy with bevacizumab...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27897178/functional-exploration-of-colorectal-cancer-genomes-using-drosophila
#11
Erdem Bangi, Claudio Murgia, Alexander G S Teague, Owen J Sansom, Ross L Cagan
The multigenic nature of human tumours presents a fundamental challenge for cancer drug discovery. Here we use Drosophila to generate 32 multigenic models of colon cancer using patient data from The Cancer Genome Atlas. These models recapitulate key features of human cancer, often as emergent properties of multigenic combinations. Multigenic models such as ras p53 pten apc exhibit emergent resistance to a panel of cancer-relevant drugs. Exploring one drug in detail, we identify a mechanism of resistance for the PI3K pathway inhibitor BEZ235...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27893714/the-lim-protein-ajuba-promotes-colorectal-cancer-cell-survival-through-suppression-of-jak1-stat1-ifit2-network
#12
H Jia, L Song, Q Cong, J Wang, H Xu, Y Chu, Q Li, Y Zhang, X Zou, C Zhang, Y E Chin, X Zhang, Z Li, K Zhu, B Wang, H Peng, Z Hou
The LIM protein AJUBA is a scaffold protein participating in the regulation of cell adhesion, mitosis, DNA damage, cell differentiation, proliferation, migration and gene transcription. However, its roles in tumorigenesis and progression are poorly defined. Here, we report that AJUBA is highly expressed in colorectal cancer (CRC) and promotes CRC cell growth in culture and in xenografted mice via an inhibition of apoptosis. AJUBA represses the expression of IFIT2 gene, an interferon-stimulated gene and a known apoptosis inducer and tumour suppressor to mediate its resistance to apoptosis...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27892920/foxk1-interaction-with-fhl2-promotes-proliferation-invasion-and-metastasis-in-colorectal-cancer
#13
M Wu, J Wang, W Tang, X Zhan, Y Li, Y Peng, X Huang, Y Bai, J Zhao, A Li, C Chen, Y Chen, H Peng, Y Ren, G Li, S Liu, J Wang
The transcriptional factor Forkhead box k1 (FOXK1) is a member of the FOX family. The abnormal expression of FOXK1 may have an important role in tumour development. Our previous studies showed that four-and-a-half LIM protein 2 (FHL2) is a critical inducer of the epithelial-to-mesenchymal transition (EMT) and invasion. However, the molecular mechanism by which FOXK1 synergizes with FHL2 tumour proliferation, EMT and metastasis is not well defined. We evaluated that messenger RNA (mRNA) and protein expression levels by quantitative RT-PCR, western blot, immunofluorescence and immunohistochemistry (IHC) assays...
November 28, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27891445/breast-cancer-with-synchronous-renal-cell-carcinoma-a-rare-presentation
#14
Ravi Arjunan, Durgesh Kumar, K V Veerendra Kumar, C S Premlatha
Primary cancer arising from multiple organs is a well known fact. Synchronous tumours have been most commonly associated with kidney cancer. Bladder, prostate, colorectal and lung cancer are the most common synchronous primaries with Renal Cell Carcinoma (RCC) identified till date. We found metachronous tumours of breast with RCC in literature search which included both metastatic tumours as well second primaries. Overall, 25 cases of metastatic breast tumours and eight cases of second primary in previously treated RCC have been reported in the literature...
October 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27888636/factors-that-influence-treatment-delay-in-patients-with-colorectal-cancer
#15
Irene Zarcos-Pedrinaci, Alberto Fernández-López, Teresa Téllez, Francisco Rivas-Ruiz, Antonio Rueda A, María Manuela Morales Suarez-Varela, Eduardo Briones, Marisa Baré, Antonio Escobar, Cristina Sarasqueta, Nerea Fernández de Larrea, Urko Aguirre, José María Quintana, Maximino Redondo, On Behalf Of The Caress-Ccr Study Group
A prospective study was performed of patients diagnosed with colorectal cancer (CRC), distinguishing between colonic and rectal location, to determine the factors that may provoke a delay in the first treatment (DFT) provided.2749 patients diagnosed with CRC were studied. The study population was recruited between June 2010 and December 2012. DFT is defined as time elapsed between diagnosis and first treatment exceeding 30 days.Excessive treatment delay was recorded in 65.5% of the cases, and was more prevalent among rectal cancer patients...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27886677/differences-in-global-dna-methylation-of-testicular-seminoma-are-not-associated-with-changes-in-histone-modifications-clinical-prognosis-braf-mutations-or-gene-expression
#16
Louise Holm Pedersen, John E Nielsen, Gedske Daugaard, Thomas V O Hansen, Ewa Rajpert-De Meyts, Kristian Almstrup
Testicular germ cell tumours of young adults are comprised of a heterogeneous group of non-seminomas and a homogeneous group of seminomas. While the majority of seminomas retain a hypo-methylated genome, a small fraction displays a highly methylated genome, resembling hyper-methylated non-seminomas. It is well established from e.g. melanoma, colorectal and thyroid cancer that a methylated phenotype can be correlated to prognosis and can be related to BRAF mutations. In the present study we investigated the global methylation level in 67 seminomas and classified them as hypo-methylated, intermediate, patchy and hyper-methylated, respectively...
November 2016: Cancer Genetics
https://www.readbyqxmd.com/read/27885555/meat-intake-cooking-methods-and-doneness-and-risk-of-colorectal-tumours-in-the-spanish-multicase-control-study-mcc-spain
#17
Jordi de Batlle, Esther Gracia-Lavedan, Dora Romaguera, Michelle Mendez, Gemma Castaño-Vinyals, Vicente Martín, Núria Aragonés, Inés Gómez-Acebo, Rocío Olmedo-Requena, José Juan Jimenez-Moleon, Marcela Guevara, Mikel Azpiri, Cristóbal Llorens-Ivorra, Guillermo Fernandez-Tardon, Jose Andrés Lorca, José María Huerta, Victor Moreno, Elena Boldo, Beatriz Pérez-Gómez, Jesús Castilla, Tania Fernández-Villa, Juan Pablo Barrio, Montserrat Andreu, Antoni Castells, Trinidad Dierssen, Jone M Altzibar, Manolis Kogevinas, Marina Pollán, Pilar Amiano
PURPOSE: Although there is convincing evidence that red and processed meat intake increases the risk of colorectal cancer (CRC), the potential role of meat cooking practices has not been established yet and could partly explain the current heterogeneity of results among studies. Therefore, we aimed to investigate the association between meat consumption and cooking practices and the risk of CRC in a population-based case-control study. METHODS: A total of 1671 CRC cases and 3095 controls recruited in Spain between September 2008 and December 2013 completing a food frequency questionnaire with a meat-specific module were included in the analyses...
November 24, 2016: European Journal of Nutrition
https://www.readbyqxmd.com/read/27884016/expression-profiling-of-budding-cells-in-colorectal-cancer-reveals-an-emt-like-phenotype-and-molecular-subtype-switching
#18
Linde De Smedt, Sofie Palmans, Daan Andel, Olivier Govaere, Bram Boeckx, Dominiek Smeets, Eva Galle, Jasper Wouters, David Barras, Madeleine Suffiotti, Jeroen Dekervel, Thomas Tousseyn, Gert De Hertogh, Hans Prenen, Sabine Tejpar, Diether Lambrechts, Xavier Sagaert
BACKGROUND: Tumour budding, described as the presence of single cells or small clusters of up to five tumour cells at the invasive margin, is established as a prognostic marker in colorectal carcinoma. In the present study, we aimed to investigate the molecular signature of tumour budding cells and the corresponding tumour bulk. METHODS: Tumour bulk and budding areas were microdissected and processed for RNA-sequencing. As little RNA was obtained from budding cells, a special low-input mRNA library preparation protocol was used...
November 24, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27883070/ph-responsive-virus-like-nanoparticles-with-enhanced-tumour-targeting-ligands-for-cancer-drug-delivery
#19
Roya Biabanikhankahdani, Noorjahan Banu Mohamed Alitheen, Kok Lian Ho, Wen Siang Tan
Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882929/soluble-il-33-receptor-sst2-inhibits-colorectal-cancer-malignant-growth-by-modifying-the-tumour-microenvironment
#20
Miho Akimoto, Riruke Maruyama, Hiroyuki Takamaru, Takahiro Ochiya, Keizo Takenaga
Interleukin-33 (IL-33) was recently shown to be involved in the inflammatory tumour microenvironment and the progression of colorectal cancer (CRC). We report here that the expression level of sST2, a soluble form of the IL-33 receptor (ST2L), is inversely associated with the malignant growth of CRC. sST2 is downregulated in high-metastatic cells compared with low-metastatic human and mouse CRC cells. Knockdown of sST2 in low-metastatic cells enhances tumour growth, metastasis and tumour angiogenesis, whereas its overexpression in high-metastatic cells suppresses these processes...
November 24, 2016: Nature Communications
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