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https://www.readbyqxmd.com/read/28545226/emergence-of-cd26-cancer-stem-cells-with-metastatic-properties-in-colorectal-carcinogenesis
#1
Alvin Ho-Kwan Cheung, Deepak Narayanan Iyer, Colin Siu-Chi Lam, Lui Ng, Sunny K M Wong, Hung-Sing Lee, Timothy Wan, Johnny Man, Ariel K M Chow, Ronnie T Poon, Roberta Pang, Wai-Lun Law
Colorectal cancer results from genetic aberrations which accumulate over a long period of time, with malignant and metastatic properties acquired at a relatively late stage. A subpopulation of CD26+ colorectal cancer stem cells are known to be implicated in metastasis. We quantified CD26+ cancer cells in 11 primary tumor samples by flow cytometry, and showed that tumors having confirmed or suspected metastases harbored a relatively high CD26+ level in these samples. We hypothesized that this subpopulation of cancer stem cells arises in the late stage of carcinogenesis from the bulk of tumor daughter cells which are CD26-...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28544777/the-prognostic-significance-of-circulating-serum-amyloid-a-and-cxc-chemokine-ligand-4-in-osteosarcoma
#2
Ricardo J Flores, Aaron J Kelly, Yiting Li, Xiang Chen, Colin McGee, Mark Krailo, Donald A Barkauskas, John Hicks, Tsz-Kwong Man
BACKGROUND: Osteosarcoma (OS) is the most common pediatric bone cancer.  Despite advances in treatment regimens, the survival rate remains 60-70%.  There is an urgent need to identify prognostic biomarkers, so that targeted therapies can be developed to improve the outcome. PROCEDURE: Our laboratory has previously identified that circulating serum amyloid A (SAA) and CXC chemokine ligand 4 (CXCL4) are upregulated in patients with OS.  In this study, we tested if they could be used as prognostic biomarkers...
May 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28542597/mir-193b-downregulated-in-ewing-sarcoma-targets-the-erbb4-oncogene-to-inhibit-anchorage-independent-growth
#3
Colin Moore, Janet K Parrish, Paul Jedlicka
Ewing Sarcoma is an aggressive, oncofusion-driven, malignant neoplasm of bone and soft tissue affecting predominantly children and young adults. Seeking to identify potential novel therapeutic targets/agents for this disease, our previous studies uncovered microRNAs regulated by EWS/Fli1, the most common oncofusion, with growth modulatory properties. In the present study, we sought to identify EWS/Fli1-repressed, growth suppressive, microRNAs potentially amenable to replacement in Ewing Sarcoma cells. Eight microRNAs (143, 153, 184, 193b, 195, 203, 206 and 223) were selected for evaluation as EWS/Fli1-repressed and underexpressed in Ewing Sarcoma cells, and reported to be growth suppressive in other pediatric or/and adult cancers...
2017: PloS One
https://www.readbyqxmd.com/read/28541575/xenobiotic-car-activators-induce-dlk1-dio3-locus-non-coding-rna-expression-in-mouse-liver
#4
Lucie Pouché, Antonio Vitobello, Michael Römer, Milica Glogovac, A Kenneth MacLeod, Heidrun Ellinger-Ziegelbauer, Magdalena Westphal, Valérie Dubost, Daniel Philipp Stiehl, Bérengère Dumotier, Alexander Fekete, Pierre Moulin, Andreas Zell, Michael Schwarz, Rita Moreno, Jeffrey T J Huang, Cliff R Elcombe, Colin J Henderson, C Roland Wolf, Jonathan G Moggs, Rémi Terranova
Derisking xenobiotic-induced non-genotoxic carcinogenesis (NGC) represents a significant challenge during the safety assessment of chemicals and therapeutic drugs. The identification of robust mechanism-based NGC biomarkers has the potential to enhance cancer hazard identification. We previously demonstrated Constitutive Androstane Receptor (CAR) and WNT signaling-dependent up-regulation of the pluripotency associated Dlk1-Dio3 imprinted gene cluster non-coding RNAs (ncRNAs) in the liver of mice treated with tumor-promoting doses of phenobarbital (PB)...
May 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28533783/progress-on-azadirachta-indica-based-biopesticides-in-replacing-synthetic-toxic-pesticides
#5
REVIEW
Suman Chaudhary, Rupinder K Kanwar, Alka Sehgal, David M Cahill, Colin J Barrow, Rakesh Sehgal, Jagat R Kanwar
Over the years, extensive use of commercially available synthetic pesticides against phytophagous insects has led to their bioaccumulation in the environment causing increased resistance and reduction in soil biodiversity. Further, 90% of the applied pesticides enter the various environmental resources as a result of run-off, exposing the farmers as well as consumers of the agricultural produce to severe health issues. Therefore, growing attention has been given toward the development of alternate environmentally friendly pesticides/insecticides that would aid an efficient pest management system and also prevent chronic exposures leading to diseases...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28523352/interim-heterogeneity-changes-measured-using-entropy-texture-features-on-t2-weighted-mri-at-3-0%C3%A2-t-are-associated-with-pathological-response-to-neoadjuvant-chemotherapy-in-primary-breast-cancer
#6
Shelley Henderson, Colin Purdie, Caroline Michie, Andrew Evans, Richard Lerski, Marilyn Johnston, Sarah Vinnicombe, Alastair M Thompson
OBJECTIVES: To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. METHODS: This was a retrospective study of 88 consenting women (age: 30-79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim)...
May 18, 2017: European Radiology
https://www.readbyqxmd.com/read/28515147/increased-t-cell-infiltration-elicited-by-erk5-deletion-in-a-pten-deficient-mouse-model-of-prostate-carcinogenesis
#7
Carolyn Loveridge, Ernest Mui, Rachana Patel, Ee Hong Tan, Imran Ahmad, Michelle Welsh, Julie Galbraith, Ann Hedley, Colin Nixon, Karen Blyth, Owen J Sansom, Hing Y Leung
Prostate cancer (PCa) does not appear to respond to immune checkpoint therapies where T cell infiltration may be a key limiting factor. Here we report evidence that ablating the growth regulatory kinase Erk5 can increase T cell infiltration in an established Pten-deficient mouse model of human PCa. Mice that were doubly mutant in prostate tissue for Pten and Erk5 (prostate DKO) exhibited a markedly increased median survival with reduced tumor size and proliferation compared to control Pten-mutant mice, the latter of which exhibited increased Erk5 mRNA expression...
May 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28487567/a-robust-in-vitro-model-for-trans-lymphatic-endothelial-migration
#8
Yanbao Xiong, C Colin Brinkman, Konrad S Famulski, Emmanuel F Mongodin, Colin J Lord, Keli L Hippen, Bruce R Blazar, Jonathan S Bromberg
Trans-endothelial migration (TEM) is essential for leukocyte circulation. While much is known about trans-blood endothelial migration, far less is known about trans-lymphatic endothelial migration. We established an in vitro system to evaluate lymphatic TEM for various cell types across primary mouse and human lymphatic endothelial cells (LEC), and validated the model for the murine LEC cell line SVEC4-10. T cells exhibited enhanced unidirectional migration from the basal (abluminal) to the apical (luminal) surface across LEC, whereas for blood endothelial cells (BEC) they migrated similarly in both directions...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28486310/vitrectomy-assisted-biopsy-for-molecular-prognostication-of-choroidal-melanoma-2-mm-or-less-in-thickness-with-a-27-gauge-cutter
#9
Aaron Nagiel, Colin A McCannel, Christian Moreno, Tara A McCannel
PURPOSE: Fine-needle aspiration biopsy of small choroidal melanomas 2 mm or less in thickness may be associated with a low biopsy yield. This report describes our center's experience using the 27-gauge vitreous cutter to perform tumor sampling in these small melanomas. METHODS: This was a retrospective analysis of all patients who underwent a 27-gauge vitreous cutter biopsy for molecular prognostication at the time of iodine-125 plaque placement for local treatment of choroidal melanoma ≤2...
October 31, 2016: Retina
https://www.readbyqxmd.com/read/28482133/estimating-the-probability-of-clonal-relatedness-of-pairs-of-tumors-in-cancer-patients
#10
Audrey Mauguen, Venkatraman E Seshan, Irina Ostrovnaya, Colin B Begg
Next generation sequencing panels are being used increasingly in cancer research to study tumor evolution. A specific statistical challenge is to compare the mutational profiles in different tumors from a patient to determine the strength of evidence that the tumors are clonally related, that is, derived from a single, founder clonal cell. The presence of identical mutations in each tumor provides evidence of clonal relatedness, although the strength of evidence from a match is related to how commonly the mutation is seen in the tumor type under investigation...
May 8, 2017: Biometrics
https://www.readbyqxmd.com/read/28470465/solubilization-and-stability-of-mitomycin-c-solutions-prepared-for-intravesical-administration
#11
Alan L Myers, Yan-Ping Zhang, Jitesh D Kawedia, Ximin Zhou, Stacey M Sobocinski, Michael J Metcalfe, Mark A Kramer, Colin P N Dinney, Ashish M Kamat
BACKGROUND: Mitomycin C (MMC) is an antitumor agent that is often administered intravesically to treat bladder cancer. Pharmacologically optimized studies have suggested varying methods to optimize delivery, with drug concentration and solution volume being the main drivers. However, these MMC concentrations (e.g. 2.0 mg/mL) supersede its solubility threshold, raising major concerns of inferior drug delivery. OBJECTIVE: In this study, we seek to confirm that the pharmacologically optimized MMC concentrations are achievable in clinical practice through careful modifications of the solution preparation methods...
June 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28466842/comprehensive-population-wide-analysis-of-lynch-syndrome-in-iceland-reveals-founder-mutations-in-msh6-and-pms2
#12
Sigurdis Haraldsdottir, Thorunn Rafnar, Wendy L Frankel, Sylvia Einarsdottir, Asgeir Sigurdsson, Heather Hampel, Petur Snaebjornsson, Gisli Masson, Daniel Weng, Reynir Arngrimsson, Birte Kehr, Ahmet Yilmaz, Stefan Haraldsson, Patrick Sulem, Tryggvi Stefansson, Peter G Shields, Fridbjorn Sigurdsson, Tanios Bekaii-Saab, Pall H Moller, Margret Steinarsdottir, Kristin Alexiusdottir, Megan Hitchins, Colin C Pritchard, Albert de la Chapelle, Jon G Jonasson, Richard M Goldberg, Kari Stefansson
Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry...
May 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28461563/circulating-tumor-cells-with-aberrant-alk-copy-number-predict-progression-free-survival-during-crizotinib-treatment-in-alk-rearranged-non-small-cell-lung-cancer-patients
#13
Emma Pailler, Marianne Oulhen, Isabelle Borget, Jordi Remon, Kirsty Ross, Nathalie Auger, Fanny Billiot, Maud Ngo Camus, Frédéric Commo, Colin R Lindsay, David Planchard, Jean-Charles Soria, Benjamin Besse, Françoise Farace
The duration and magnitude of clinical response are unpredictable in ALK-rearranged non-small cell lung cancer (NSCLC) patients treated with crizotinib, although all patients invariably develop resistance. Here, we evaluated whether circulating tumor cells (CTC) with aberrant ALK-FISH patterns [ALK-rearrangement, ALK-copy number gain (ALK-CNG)] monitored on crizotinib could predict progression-free survival (PFS) in a cohort of ALK-rearranged patients. Thirty-nine ALK-rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospectively...
May 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28460469/identification-of-microrna-885-5p-as-a-novel-regulator-of-tumor-metastasis-by-targeting-cpeb2-in-colorectal-cancer
#14
Colin Siu-Chi Lam, Lui Ng, Ariel Ka-Man Chow, Timothy Ming-Hun Wan, Simon Yau, Nathan Shiu-Man Cheng, Sunny Kit-Man Wong, Johnny Hon-Wai Man, Oswens Siu-Hung Lo, Dominic Chi-Chung Foo, Jensen Tung-Chung Poon, Roberta Wen-Chi Pang, Wai-Lun Law
Colorectal cancer is the third most common cancer in the world and liver is the most frequent site of distant metastasis with poor prognosis. The aim of this study is to investigate microRNAs leading to liver metastasis. We applied microarray analysis and quantitative PCR to identify and validate dysregulated miRNAs in liver metastases when compared to primary CRCs. Functional significance and the underlying molecular mechanism of selected miRNA was demonstrated by a series of in vitro and in vivo assays. Our microarray analysis and subsequent quantitative PCR validation revealed that miR-885-5p was strongly up-regulated in liver metastases and in CRC cell-lines derived from distant metastases...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28460457/the-vitamin-d-receptor-is-involved-in-the-regulation-of-human-breast-cancer-cell-growth-via-a-ligand-independent-function-in-cytoplasm
#15
Trupti Trivedi, Yu Zheng, Pierrick G J Fournier, Sreemala Murthy, Sutha John, Suzanne Schillo, Colin R Dunstan, Khalid S Mohammad, Hong Zhou, Markus J Seibel, Theresa A Guise
Vitamin D has pleiotropic effects on multiple tissues, including malignant tumors. Vitamin D inhibits breast cancer growth through activation of the vitamin D receptor (VDR) and via classical nuclear signaling pathways. Here, we demonstrate that the VDR can also function in the absence of its ligand to control behaviour of human breast cancer cells both outside and within the bone microenvironment. Stable shRNA expression was used to knock down VDR expression in MCF-7 cells, generating two VDR knockdown clonal lines...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28460430/metabolic-heterogeneity-signature-of-primary-treatment-na%C3%A3-ve-prostate-cancer
#16
Dong Lin, Susan L Ettinger, Sifeng Qu, Hui Xue, Noushin Nabavi, Stephen Yiu Chuen Choi, Robert H Bell, Fan Mo, Anne M Haegert, Peter W Gout, Neil Fleshner, Martin E Gleave, Michael Pollak, Colin C Collins, Yuzhuo Wang
To avoid over- or under-treatment of primary prostate tumours, there is a critical need for molecular signatures to discriminate indolent from aggressive, lethal disease. Reprogrammed energy metabolism is an important hallmark of cancer, and abnormal metabolic characteristics of cancers have been implicated as potential diagnostic/prognostic signatures. While genomic and transcriptomic heterogeneity of prostate cancer is well documented and associated with tumour progression, less is known about metabolic heterogeneity of the disease...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28456991/lysosomal-biology-in-cancer
#17
Colin Fennelly, Ravi K Amaravadi
Cells depend on the lysosome for sequestration and degradation of macromolecules in order to maintain metabolic homeostasis. These membrane-enclosed organelles can receive intracellular and extracellular cargo through endocytosis, phagocytosis, and autophagy. Lysosomes establish acidic environments to activate enzymes that are able to break down biomolecules engulfed through these various pathways. Recent advances in methods to study the lysosome have allowed the discovery of extended roles for the lysosome in various diseases, including cancer, making it an attractive and targetable node for therapeutic intervention...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28450426/analysis-of-circulating-cell-free-dna-identifies-multi-clonal-heterogeneity-of-brca2-reversion-mutations-associated-with-resistance-to-parp-inhibitors
#18
David Quigley, Joshi J Alumkal, Alexander W Wyatt, Vishal Kothari, Adam Foye, Paul Lloyd, Rahul Aggarwal, Won Kim, Eric Lu, Jacob Schwartzman, Kevin Beja, Matti Annala, Rajdeep Das, Morgan Diolaiti, Colin C Pritchard, George V Thomas, Scott A Tomlins, Karen E Knudsen, Christopher J Lord, Charles J Ryan, Jack Youngren, Tomasz M Beer, Alan Ashworth, Eric J Small, Felix Y Feng
Approximately 20% of metastatic prostate cancers harbor mutations in genes required for DNA repair by homologous recombination (HRR) such as BRCA2. HRR defects confer synthetic lethality to PARP inhibitors (PARPi) such as olaparib and talazoparib. In ovarian or breast cancers, olaparib resistance has been associated with HRR restoration, including by BRCA2 mutation reversion. Whether similar mechanisms operate in prostate cancer, and could be detected in liquid biopsies, is unclear. Here, we identify BRCA2 reversion mutations associated with olaparib and talazoparib resistance in prostate cancer patients...
April 27, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28450390/british-society-of-gastroenterology-position-statement-on-serrated-polyps-in-the-colon-and-rectum
#19
James E East, Wendy S Atkin, Adrian C Bateman, Susan K Clark, Sunil Dolwani, Shara N Ket, Simon J Leedham, Perminder S Phull, Matt D Rutter, Neil A Shepherd, Ian Tomlinson, Colin J Rees
Serrated polyps have been recognised in the last decade as important premalignant lesions accounting for between 15% and 30% of colorectal cancers. There is therefore a clinical need for guidance on how to manage these lesions; however, the evidence base is limited. A working group was commission by the British Society of Gastroenterology (BSG) Endoscopy section to review the available evidence and develop a position statement to provide clinical guidance until the evidence becomes available to support a formal guideline...
April 27, 2017: Gut
https://www.readbyqxmd.com/read/28448657/association-between-slc16a5-genetic-variation-and-cisplatin-induced-ototoxic-effects-in-adult-patients-with-testicular-cancer
#20
Britt I Drögemöller, Jose G Monzon, Amit P Bhavsar, Adrienne E Borrie, Beth Brooks, Galen E B Wright, Geoffrey Liu, Daniel J Renouf, Christian K Kollmannsberger, Philippe L Bedard, Folefac Aminkeng, Ursula Amstutz, Claudette A Hildebrand, Erandika P Gunaretnam, Carol Critchley, Zhuo Chen, Liam R Brunham, Michael R Hayden, Colin J D Ross, Karen A Gelmon, Bruce C Carleton
Importance: Cisplatin-induced ototoxic effects are an important complication that affects testicular cancer survivors as a consequence of treatment. The identification of genetic variants associated with this adverse drug reaction will further our mechanistic understanding of its development and potentially lead to strategies to prevent ototoxic effects. Objective: To identify the genetic variants associated with cisplatin-induced ototoxic effects in adult testicular cancer patients...
April 27, 2017: JAMA Oncology
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