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https://www.readbyqxmd.com/read/28174005/the-expression-of-cancer-stem-cell-markers-in-human-colorectal-carcinoma-cells-in-a-microenvironment-dependent-manner
#1
Vaidotas Stankevicius, Linas Kunigenas, Edvinas Stankunas, Karolina Kuodyte, Egle Strainiene, Jonas Cicenas, Narimantas E Samalavicius, Kestutis Suziedelis
Numerous lines of evidence support the hierarchical model of cancer development and tumor initiation. According to the theory, cancer stem cells play a crucial role in the formation of the tumor and should be targeted for more effective anticancer treatment. However, cancer stem cells quickly loose their characteristics when propagated as 2D cell culture, indicating that the 2D cell culture does not provide the appropriate settings to maintain an in vivo environment. In this study we have investigated the expression of self-renewal, cancer stem cell and epithelial to mesenchymal transition markers after the transfer of human colorectal carcinoma cell DLD1 and HT29 lines from 2D cell cultures to scaffold-attached laminin rich extracellular matrix and scaffold-free multicellular spheroid 3D culture models...
February 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28154246/steering-of-carcinoma-progression-by-the-yin-yang-interaction-of-stat1-stat3
#2
Karlheinz Friedrich, Helmut Dolznig, Xiaonan Han, Richard Moriggl
STAT1/STAT3 transcription factors are important regulators for development of normal, infected or inflammed cells. They are also critically involved in the progression of various malignant tumours, including epithelial-derived carcinomas. Here, we focus on colorectal cancer (CRC) insights for STAT1/3, where controversial functions for STAT3 were reported. For a long time STAT3 has been regarded as a driver of tumour malignancy and its activation was associated with negative clinical outcome. In contrast, STAT1 was generally viewed as an independent tumour suppressor and positive prognostic marker...
February 2, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28138402/construction-and-analysis-of-tissue-microarrays-in-the-era-of-digital-pathology-a-pilot-study-targeting-cdx1-and-cdx2-in-a-colon-cancer-cohort-of-612-patients
#3
Sarah Nolte, Inti Zlobec, Alessandro Lugli, Werner Hohenberger, Roland Croner, Susanne Merkel, Arndt Hartmann, Carol I Geppert, Tilman T Rau
CDX1 and CDX2 are possibly predictive biomarkers in colorectal cancer. We combined digitally-guided (next generation) TMA construction (ngTMA) and the utility of digital image analysis (DIA) to assess accuracy, tumour heterogeneity and the selective impact of different combined intensity-percentage levels on prognosis.CDX1 and CDX2 immunohistochemistry was performed on ngTMAs covering normal tissue, tumour centre and invasive front. The percentages of all epithelial cells per staining intensity per core were analysed digitally...
January 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28127763/mutational-signature-analysis-identifies-mutyh-deficiency-in-colorectal-cancers-and-adrenocortical-carcinomas
#4
Camilla Pilati, Jayendra Shinde, Ludmil B Alexandrov, Guillaume Assié, Thierry André, Zofia Hélias-Rodzewicz, Romain Doucoudray, Delphine Le Corre, Jessica Zucman-Rossi, Jean-François Emile, Jérôme Bertherat, Eric Letouzé, Pierre Laurent-Puig
Germline alterations in DNA repair genes are implicated in cancer predisposition and can result in characteristic mutational signatures. However, specific mutational signatures associated with base excision repair (BER) defects remain to be characterized. Here, by analysing a series of colorectal cancers (CRC) using exome sequencing, we identified a particular spectrum of somatic mutations characterized by an enrichment of C > A transversions in NpCpA or NpCpT contexts, in three tumours from a MUTYH-associated polyposis (MAP) patient and in two cases harbouring pathogenic germline MUTYH mutations...
January 27, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28114961/mif-cd74-axis-is-a-target-for-novel-therapies-in-colon-carcinomatosis
#5
Fabio Bozzi, Angela Mogavero, Luca Varinelli, Antonino Belfiore, Giacomo Manenti, Claudio Caccia, Chiara C Volpi, Galina V Beznoussenko, Massimo Milione, Valerio Leoni, Annunziata Gloghini, Alexandre A Mironov, Ermanno Leo, Silvana Pilotti, Marco A Pierotti, Italia Bongarzone, Manuela Gariboldi
BACKGROUND: Strategies aimed at obtaining a complete cytoreduction are needed to improve long-term survival for patients with colorectal cancer peritoneal carcinomatosis (CRC-pc). METHODS: We established organoid models from peritoneal metastases of two naïve CRC patients. A standard paraffin inclusion was conducted to compare their 3D structure and immunohistochemical profile with that of the corresponding surgical samples. RNA expression levels of the CRC stem cell marker LGR5 was measured by in situ hybridization...
January 23, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28106826/colorectal-carcinoma-a-general-overview-and-future-perspectives-in-colorectal-cancer
#6
REVIEW
Inés Mármol, Cristina Sánchez-de-Diego, Alberto Pradilla Dieste, Elena Cerrada, María Jesús Rodriguez Yoldi
Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%-5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28081548/serum-ldh-predicts-benefit-from-bevacizumab-beyond-progression-in-metastatic-colorectal-cancer
#7
Federica Marmorino, Lisa Salvatore, Cecilia Barbara, Giacomo Allegrini, Lorenzo Antonuzzo, Gianluca Masi, Fotios Loupakis, Beatrice Borelli, Silvana Chiara, Maria Chiara Banzi, Emanuela Miraglio, Domenico Amoroso, Francesco Dargenio, Andrea Bonetti, Angelo Martignetti, Myriam Paris, Daniela Tomcikova, Luca Boni, Alfredo Falcone, Chiara Cremolini
BACKGROUND: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. METHODS: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy...
January 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28067827/clinical-significance-and-prognostic-relevance-of-microsatellite-instability-in-sporadic-colorectal-cancer-patients
#8
REVIEW
Angelika Copija, Dariusz Waniczek, Andrzej Witkoś, Katarzyna Walkiewicz, Ewa Nowakowska-Zajdel
Microsatellite instability (MSI) is a marker of the replication error phenotype. It is caused by impaired DNA mismatch repair processes (MMR), resulting in ineffectiveness of the mechanisms responsible for the DNA replication precision and postreplicative DNA repair. MSI underlies the pathogenesis of 10%-20% of colorectal cancer (CRC) cases. The data about the potential value of MMR status as a predictive factor for 5-fluorouracil (FU)-based chemotherapy remain unclear. According to National Comprehensive Cancer Network updated guidelines, MSI testing is recommended for all patients with stage II CRC because patients with MSI-H (high-frequency MSI) tumour may have a good prognosis and obtain no benefit from 5-FU-based adjuvant chemotherapy...
January 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28028388/detection-of-cancer-stem-cells-in-colorectal-cancer-histopathological-and-immunohistochemical-study
#9
Nour El Hoda S Ismaiel, Walid M Sharaf, Dina O Helmy, Mona M Zaki, Manal A Badawi, Ahmed S A Soliman
BACKGROUND: Growing evidence supports the notion that the onset of tumorigenesis could occur through cancer stem cells (CSCs). These tumour cells show low proliferative rates, high self-renewal capacity, propensity to differentiate into active proliferating tumour cells & resistance to chemoradiotherapy thus, possibly causing local recurrences & metastasis formation. CD44 has been used as a marker to isolate CSCs from colorectal carcinoma (CRC). AIM: To investigate the immunohistochemical expression of cancer stem cells marker (CD44) in CRC and correlate its expression with the clinicopathological aspects, TNM staging and modified Dukes' classification...
December 15, 2016: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28028292/glypican-3-is-useful-but-not-superior-to-hep-par-1-in-differentiating-hepatocellular-carcinoma-from-other-liver-tumours
#10
A M Pour, N Masir, I M Rose
To assess the diagnostic utility of glypican-3 (GPC-3) in comparison to Hep Par 1 in the diagnosis of liver tumours, a cross-sectional study involving 66 resected liver tumours were tested for the protein expression of these markers by immunohistochemistry using monoclonal antibodies. Of the 66 cases, 26 (39.4%) were hepatocellular carcinoma (HCC), 4 (6.1%) were intrahepatic cholangiocarcinoma and 36 (54.5%) were metastatic tumours. Hep Par 1 and GPC-3 expressions in HCC were 24/26 (92.3%) and 19/26 (73.1%) respectively...
December 2016: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/28018106/elevated-fibrinogen-plasma-level-is-not-an-independent-predictor-of-poor-prognosis-in-a-large-cohort-of-western-patients-undergoing-surgery-for-colorectal-cancer
#11
Corrado Pedrazzani, Guido Mantovani, Gian Luca Salvagno, Elisabeth Baldiotti, Andrea Ruzzenente, Calogero Iacono, Giuseppe Lippi, Alfredo Guglielmi
AIM: To evaluate the clinical significance of the preoperative fibrinogen plasma level as a prognostic marker after surgery for colorectal cancer. METHODS: This retrospective study analysed 652 patients undergoing surgery for stage I-IV colorectal cancer between January 2005 and December 2012, at the Division of General Surgery A, University of Verona Hospital Trust, in whom preoperative fibrinogen plasma values were assessed at baseline. Fibrinogen is involved in tumourigenesis as well as tumour progression in several malignancies...
December 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27983717/evaluation-of-methylation-biomarkers-for-detection-of-circulating-tumor-dna-and-application-to-colorectal-cancer
#12
Susan M Mitchell, Thu Ho, Glenn S Brown, Rohan T Baker, Melissa L Thomas, Aidan McEvoy, Zheng-Zhou Xu, Jason P Ross, Trevor J Lockett, Graeme P Young, Lawrence C LaPointe, Susanne K Pedersen, Peter L Molloy
Solid tumors shed DNA into circulation, and there is growing evidence that the detection of circulating tumor DNA (ctDNA) has broad clinical utility, including monitoring of disease, prognosis, response to chemotherapy and tracking tumor heterogeneity. The appearance of ctDNA in the circulating cell-free DNA (ccfDNA) isolated from plasma or serum is commonly detected by identifying tumor-specific features such as insertions, deletions, mutations and/or aberrant methylation. Methylation is a normal cell regulatory event, and since the majority of ccfDNA is derived from white blood cells (WBC), it is important that tumour-specific DNA methylation markers show rare to no methylation events in WBC DNA...
December 15, 2016: Genes
https://www.readbyqxmd.com/read/27943617/relation-between-postoperative-ileus-and-anastomotic-leakage-after-colorectal-resection-a-post-hoc-analysis-of-a-prospective-randomized-controlled-trial
#13
E G Peters, M Dekkers, F W van Leeuwen-Hilbers, F Daams, K W E Hulsewé, W J de Jonge, W A Buurman, M D P Luyer
AIM: Anastomotic leakage (AL) following abdominal surgery is a critical determinant of postoperative recovery, of which the aetiology is largely unknown. Interestingly, interventions aimed at reducing the inflammatory response and postoperative ileus (POI) have an unexpected effect on AL. The aim of this study was to investigate the relation of POI with inflammation and AL after colorectal resection. METHOD: A post-hoc analysis of a prospective RCT, in which patients underwent a colorectal resection was performed...
December 10, 2016: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
https://www.readbyqxmd.com/read/27922044/from-tumour-heterogeneity-to-advances-in-precision-treatment-of-colorectal-cancer
#14
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/27893714/the-lim-protein-ajuba-promotes-colorectal-cancer-cell-survival-through-suppression-of-jak1-stat1-ifit2-network
#15
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/27884016/expression-profiling-of-budding-cells-in-colorectal-cancer-reveals-an-emt-like-phenotype-and-molecular-subtype-switching
#16
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...
January 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/27880730/loss-of-zg16-is-regulated-by-mir-196a-and-contributes-to-stemness-and-progression-of-colorectal-cancer
#17
Xiaobing Chen, Peng Du, Junjun She, Liang Cao, Yingchao Li, Hongping Xia
Colorectal cancer (CRC) is one of the most common malignant tumour and the leading cause of cancer-related mortality worldwide. Clarification of the mechanism that underlies CRC tumorigenesis and progression therefore is urgently needed ffor developing novel therapies. Through analysis of The Cancer Genome Atlas (TCGA) dataset, we identified an interesting gene, ZG16, which is significantly decreased in CRC samples compared to adjacent non-tumor tissues and associated with prognosis of patients. We found that the expression of ZG16 correlated with CRC related genes which were regulated by APC/CTNNB1 pathway...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27822332/extracellular-matrix-gene-expression-profiling-using-microfluidics-for-colorectal-carcinoma-stratification
#18
Christopher J Hayes, Catriona M Dowling, Susan Dwane, Mary E McCumiskey, Shona M Tormey, B Anne Merrigan, John C Coffey, Patrick A Kiely, Tara M Dalton
In cancer, biomarkers have many potential applications including generation of a differential diagnosis, prediction of response to treatment, and monitoring disease progression. Many molecular biomarkers have been put forward for different diseases but most of them do not possess the required specificity and sensitivity. A biomarker with a high sensitivity has a low specificity and vice versa. The inaccuracy of the biomarkers currently in use has led to a compelling need to identify more accurate markers with diagnostic and prognostic significance...
September 2016: Biomicrofluidics
https://www.readbyqxmd.com/read/27797228/evaluation-of-mt1xt20-single-quasi-monomorphic-mononucleotide-marker-for-characterizing-microsatellite-instability-in-persian-lynch-syndrome-patients
#19
Najmeh Farahani, Parvaneh Nikpou, Mohammad Hassan Emami, Morteza Hashemzadeh, Mehrdad Zeinalian, Seyed Shervin Shariatpanahi, Rasoul Salehi
BACKGROUND: Colorectal malignancies with high microsatellite instability (MSI-H), either hereditary (Lynch syndrome) or sporadic, demonstrate better prognosis and altered response to 5FU chemotherapy. It is now recommended to perform MSI testing for all new cases of colorectal cancer regardless of being categorized as hereditary or sporadic. For MSI detection, immunohistochemistry or PCR-based protocols using a cohort of various sets of STR markers are recommended. Here we aimed to evaluate a simplified protocol using just a single STR marker, MT1XT20 mononucleotide repeat, for detection of MSI in Lynch syndrome patients...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27766737/micrometastasis-in-colorectal-cancer-does-it-affect-staging
#20
Gholamreza Mohajeri, Kavak Hejab, Saba Sheikhbahaei, Mohammadreza Mohajeri, Negar Niknam, Alireza Mohammadi
BACKGROUND: Micrometastasis (MM) in colorectal cancer (CRC) is not considered in tumour-node-metastasis (TNM) staging currently and also the prognostic significance of these occult tumoural cells is not proven yet. This study was designed to find whether MM to bone marrow (BM) and/or liver cause upstaging of the tumour according to conventional staging system and if it may alter the survival rate. METHODS: Thirty-eight CRC patients who were candidates of surgical procedure were enrolled in our cross-sectional study...
October 21, 2016: ANZ Journal of Surgery
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