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https://www.readbyqxmd.com/read/28210747/extent-of-field-change-in-colorectal-cancers-with-braf-mutation
#1
Aaron Poh, Heidi Sian Ying Chang, Kok Yang Tan, Xin Xiu Sam, Avery Khoo, Shoa Nian Choo, Min En Nga, Wei Keat Wan
INTRODUCTION: Sporadic colorectal cancers with BRAF mutations constitute two distinct subgroups of colorectal cancers. Recent studies have linked the presence of the BRAF mutation to a familial inheritance pattern. This was a proof-of-concept study that aimed to examine: (a) the extent of field change in sporadic colorectal cancers with BRAF mutation; and (b) the extent of resection margins required and the pattern of DNA mismatch repair protein loss in these tumours. METHODS: Eight microsatellite instability-high (MSI-H) tumours with positive BRAF mutation from an existing histopathological database were selected for BRAF mutation and mismatch repair protein analysis...
February 17, 2017: Singapore Medical Journal
https://www.readbyqxmd.com/read/28199979/atm-mutations-and-e-cadherin-expression-define-sensitivity-to-egfr-targeted-therapy-in-colorectal-cancer
#2
Anna-Lena Geißler, Miriam Geißler, Daniel Kottmann, Lisa Lutz, Christiane D Fichter, Ralph Fritsch, Britta Weddeling, Frank Makowiec, Martin Werner, Silke Lassmann
EGFR-targeted therapy is a key treatment approach in patients with RAS wildtype metastatic colorectal cancers (CRC). Still, also RAS wildtype CRC may be resistant to EGFR-targeted therapy, with few predictive markers available for improved stratification of patients. Here, we investigated response of 7 CRC cell lines (Caco-2, DLD1, HCT116, HT29, LS174T, RKO, SW480) to Cetuximab and correlated this to NGS-based mutation profiles, EGFR promoter methylation and EGFR expression status as well as to E-cadherin expression...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197377/pd-l1-cd274-promoter-methylation-predicts-survival-in-colorectal-cancer-patients
#3
Diane Goltz, Heidrun Gevensleben, Jörn Dietrich, Dimo Dietrich
This study evaluates promoter methylation of the programmed cell death ligand 1 (PD-L1) as a biomarker in a cohort of 383 colorectal cancer patients. PD-L1 methylation (mPD-L1) was inversely correlated with PD-L1 mRNA expression (p = 0.001) and was associated with significantly shorter overall survival (OS, p = 0.003) and recurrence-free survival (RFS, p < 0.001). In age-stratified multivariate Cox proportional hazards analyses including sex, tumor, nodal, distant metastasis categories, microsatellite instability (MSI)-status, and PD-L1 mRNA, mPD-L1 is classified as an independent prognostic factor (OS: p = 0...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28195261/immunohistochemical-evaluation-of-mismatch-repair-proteins-in-colorectal-carcinoma-the-aifeg-gipad-proposal
#4
A Remo, M Fassan, G Lanza
Microsatellite instability (MSI) is a hypermutable phenotype that usually arises from either a germline mutation in components of the mismatch repair (MMR) machinery (i.e. hMLH1, MSH2, MSH6 and PMS2) in patients with Lynch syndrome (LS) or somatic hypermethylation of the hMLH1 promoter in sporadic carcinomas. In all colorectal cancers (CRC) is possible to identify the MMR deficiency through protein expression by immunoistochemistry (IHC). Recently, the predictive role of MMR deficiency in reduced chemotherapy benefit and the introduction of universal screening for Lynch syndrome suggest to include MMR testing into routine clinical practice...
September 2016: Pathologica
https://www.readbyqxmd.com/read/28194988/personal-information-from-latent-fingerprints-using-desorption-electrospray-ionization-mass-spectrometry-and-machine-learning
#5
Zhenpeng Zhou, Richard N Zare
Desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was applied to latent fingerprints to obtain not only spatial patterns but also chemical maps. Samples with similar lipid compositions as those of the fingerprints were collected by swiping a glass slide across the forehead of consenting adults. A machine learning model called gradient boosting tree ensemble (GDBT) was applied to the samples that allowed us to distinguish between different genders, ethnicities, and ages (within 10 years)...
January 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28194740/potential-of-burkholderia-seminalis-tc3-4-2r3-as-biocontrol-agent-against-fusarium-oxysporum-evaluated-by-mass-spectrometry-imaging
#6
Francisca Diana da Silva Araújo, Welington Luiz Araújo, Marcos Nogueira Eberlin
Species of genus Burkholderia display different interaction profiles in the environment, causing either several diseases in plants and animals or being beneficial to some plants, promoting their growth, and suppressing phytopathogens. Burkholderia spp. also produce many types of biomolecules with antimicrobial activity, which may be commercially used to protect crops of economic interest, mainly against fungal diseases. Herein we have applied matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to investigate secondary metabolites produced by B...
February 13, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28193015/derivatization-strategies-for-the-detection-of-triamcinolone-acetonide-in-cartilage-by-using-matrix-assisted-laser-desorption-ionization-mass-spectrometry-imaging
#7
Florian P Y Barré, Bryn Flinders, João P Garcia, Imke Jansen, Lennart R S Huizing, Tiffany Porta, Laura B Creemers, Ron M A Heeren, Berta Cillero-Pastor
Osteoarthritis (OA), characterized by degeneration of the cartilaginous tissue in articular joints, severely impairs mobility in many people worldwide. The degeneration is thought to be mediated by inflammatory processes occurring in the tissue of the joint, including the cartilage. Intra-articular administered triamcinolone acetonide (TAA) is one of the drug treatments employed to ameliorate the inflammation and pain that characterizes OA. However, the penetration and distribution of TAA into the avascular cartilage is not well understood...
December 20, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28190955/multi-level-correlates-of-safer-conception-methods-awareness-and-attitudes-among-ugandan-hiv-clients-with-fertility-intentions
#8
Glenn J Wagner, Mahlet A Woldetsadik, Jolly Beyeza-Kashesya, Kathy Goggin, Deborah Mindry, Sarah Finocchario-Kessler, Sarah Khanakwa, Rhoda K Wanyenze
Many people living with HIV desire childbearing, but low cost safer conception methods (SCM) such as timed unprotected intercourse (TUI) and manual self-insemination (MSI) are rarely used. We examined awareness and attitudes towards SCM, and the correlates of these constructs among 400 HIV clients with fertility intentions in Uganda. Measures included awareness, self-efficacy, and motivation regarding SCM, as well as demographics, health management, partner and provider characteristics. Just over half knew that MSI (53%) and TUI (51%) reduced transmission risk during conception, and 15% knew of sperm washing and pre-exposure prophylaxis...
March 2016: African Journal of Reproductive Health
https://www.readbyqxmd.com/read/28188274/spatial-and-temporal-mapping-of-key-lipid-species-in-brassica-napus-seeds
#9
Helen K Woodfield, Drew Sturtevant, Ljudmilla Borisjuk, Eberhard Munz, Irina A Guschina, Kent D Chapman, John L Harwood
The regulation of lipid synthesis in oil seeds is still not fully understood. Oilseed rape is the third most productive vegetable oil crop on the global market. Therefore, increasing our understanding of lipid accumulation in oilseed rape seeds is of great economic, as well as intellectual, importance. Matrix-assisted laser/desorption ionisation - mass spectrometry imaging (MALDI-MSI) is a technique that allows the mapping of metabolites directly onto intact biological tissues, giving a spatial context to metabolism...
February 10, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28188185/response-to-pd-1-blockade-in-microsatellite-stable-metastatic-colorectal-cancer-harboring-a-pole-mutation
#10
Jun Gong, Chongkai Wang, Peter P Lee, Peiguo Chu, Marwan Fakih
Recent clinical evidence has demonstrated that microsatellite instability (MSI) or defective mismatch repair (MMR) and high tumor mutational load can predict response to the programmed cell death 1 (PD-1) receptor inhibitor pembrolizumab in metastatic colorectal cancer (mCRC). Mutations in polymerase ε (POLE), a DNA polymerase involved in DNA replication and repair, contribute to an ultramutated but microsatellite stable (MSS) phenotype in colorectal tumors that is uniquely distinct from MSI tumors. This report presents the first case in the literature describing a clinical response to pembrolizumab in an 81-year-old man with treatment-refractory mCRC characterized by an MSS phenotype and POLE mutation identified on genomic profiling by next-generation sequencing...
February 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28185288/metformin-effects-on-head-and-neck-squamous-carcinoma-microenvironment-window-of-opportunity-trial
#11
Joseph Curry, Jennifer Johnson, Patrick Tassone, Marina Domingo Vidal, Diana Whitaker Menezes, John Sprandio, Mehri Mollaee, Paolo Cotzia, Ruth Birbe, Zhao Lin, Kurren Gill, Elizabeth Duddy, Tingting Zhan, Benjamin Leiby, Michelle Reyzer, David Cognetti, Adam Luginbuhl, Madalina Tuluc, Ubaldo Martinez-Outschoorn
OBJECTIVE: The tumor microenvironment frequently displays abnormal cellular metabolism, which contributes to aggressive behavior. Metformin inhibits mitochondrial oxidative phosphorylation, altering metabolism. Though the mechanism is unclear, epidemiologic studies show an association between metformin use and improved outcomes in head and neck squamous cell carcinoma (HNSCC). We sought to determine if metformin alters metabolism and apoptosis in HNSCC tumors. STUDY DESIGN: Window of opportunity trial of metformin between diagnostic biopsy and resection...
February 10, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28178681/molecular-profiling-of-metastatic-colorectal-tumors-using-next-generation-sequencing-a-single-institution-experience
#12
Jun Gong, May Cho, Marvin Sy, Ravi Salgia, Marwan Fakih
BACKGROUND: Recent molecular characterization of colorectal tumors has identified several molecular alterations of interest that are considered targetable in metastatic colorectal cancer (mCRC). METHODS: We conducted a single-institution, retrospective study based on comprehensive genomic profiling of tumors from 138 patients with mCRC using next-generation sequencing (NGS) via FoundationOne. RESULTS: Overall, RAS mutations were present in 51...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176205/correlation-between-germline-mutations-in-mmr-genes-and-microsatellite-instability-in-ovarian-cancer-specimens
#13
Mohammad R Akbari, Shiyu Zhang, Deborah Cragun, Ji-Hyun Lee, Domenico Coppola, John McLaughlin, Harvey A Risch, Barry Rosen, Patricia Shaw, Thomas A Sellers, Joellen Schildkraut, Steven A Narod, Tuya Pal
A high proportion of ovarian cancers from women who carry germline mutations in mismatch repair (MMR) genes demonstrate microsatellite instability (MSI). The utility of pre-screening ovarian cancer specimens for MSI to identify potential patients for germline screening for MMR mutations is uncertain. 656 women with malignant ovarian cancer underwent both MSI testing and germline mutation testing for large rearrangements in three MMR genes, MLH1, MSH2 and MSH6. Germline DNA sequencing data for the same genes was available...
February 7, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28173936/left-sided-early-onset-colorectal-carcinomas-a-sporadic-neoplasm-with-aggressive-behavior
#14
Emanuela Pilozzi, Laura Lorenzon, Simone Lo Baido, Mario Ferri, Enrico Duranti, Flavio Fochetti, Paolo Mercantini, Giovanni Ramacciato, Genoveffa Balducci, Luigi Ruco
BACKGROUND: Early onset (≤50y) colorectal carcinomas (EO-CRCs) are increasing in incidence according to epidemiological data. We investigated clinical-pathological, molecular features and outcomes of 62 left sided EO-CRCs (EOLS-CRCs) and compared them to a group of late onset (≥65) LS-CRCs (LOLS-CRCs). MATERIALS AND METHODS: Samples were evaluated for pathological features and microsatellite instability (MSI). Overall survival (OS), disease free survival (DFS) and disease specific survival were evaluated in both groups...
January 31, 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/28165633/back-to-the-future-routine-morphological-assessment-of-the-tumour-microenvironment-is-prognostic-in-stage-ii-iii-colon-cancer-in-a-large-population-based-study
#15
Seán O Hynes, Helen G Coleman, Paul J Kelly, Steven Irwin, Roisin F O'Neill, Ronan T Gray, Claire McGready, Philip D Dunne, Stephen McQuaid, Jacqueline A James, Manuel Salto-Tellez, Maurice B Loughrey
AIMS: Both morphological and molecular approaches have highlighted the biological and prognostic importance of the tumour microenvironment in colorectal cancer (CRC). Despite this, microscopic assessment of tumour microenvironment has not been adopted into routine practice. METHODS AND RESULTS: Based on existing evidence, we selected specific morphological features relating to peritumoral inflammatory and stromal responses, agreed criteria for scoring, and assessed these in representative H&E-stained whole tumour sections, from a population-based cohort of 445 stage II/III colon cancer cases...
February 6, 2017: Histopathology
https://www.readbyqxmd.com/read/28160106/variable-levels-of-long-noncoding-rna-expression-in-dna-mismatch-repair-proficient-early-stage-colon-cancer
#16
Qian Li, Nanshan Li, Yueqiong Lao, Wu Lin, Guojun Jiang, Nan Wei, Canghai Wang, Kuiliang Liu, Jing Wu
BACKGROUND: Long noncoding RNAs (lncRNAs) have been suggested to be biomarkers for diagnosis and prognosis of sporadic colorectal cancer. AIMS: This study aimed to characterize the expression profile of lncRNAs in DNA mismatch repair-proficient (pMMR) early-stage colon cancer (CC). METHODS: The microsatellite instability (MSI) status was examined by a multiplex PCR. The expression of lncRNA and mRNA was analyzed by microarrays. The differentially expressed lncRNAs and mRNAs were determined by bioinformatic analyses and validated in 44 CC samples and 32 non-tumor colonic specimens by quantitative real-time polymerase chain reaction (qRT-PCR)...
February 3, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28157191/mass-spectrometry-imaging-of-kidney-tissue-sections-of-rat-subjected-to-unilateral-ureteral-obstruction
#17
Huihui Liu, Wan Li, Qing He, Jinjuan Xue, Jiyun Wang, Caiqiao Xiong, Xiaoping Pu, Zongxiu Nie
Chronic kidney disease (CKD) poses a serious threat to the quality of human life and health with an increasing incidence worldwide. Renal fibrosis is closely related to CKD and regarded as the final common pathophysiological pathway in most cases of end-stage renal diseases. Elucidating the mechanisms underlying renal fibrosis and developing novel therapeutic strategies are of great importance. Herein, matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) based on 1, 5-diaminonaphthalene hydrochloride was applied to the rat model of unilateral ureteral obstruction (UUO) to investigate metabolic changes during renal fibrosis...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28155873/alteration-of-multiple-leukocyte-gene-expression-networks-is-linked-with-magnetic-resonance-markers-of-prognosis-after-acute-st-elevation-myocardial-infarction
#18
A Teren, H Kirsten, F Beutner, M Scholz, L M Holdt, D Teupser, M Gutberlet, J Thiery, G Schuler, I Eitel
Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15-25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO)...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28154861/application-of-imaging-mass-spectrometry-approaches-to-facilitate-metal-based-anticancer-drug-research
#19
Ronald F S Lee, Sarah Theiner, Anders Meibom, Gunda Koellensperger, Bernhard K Keppler, Paul J Dyson
Mass spectrometry imaging is being increasingly used in metal-based anticancer drug development to study elemental and/or molecular drug distributions in different biological systems. The main analytical tools employed are SIMS (especially nanoSIMS), LA-ICP-MSI and MALDI-MSI as well as a combination of complementary imaging techniques. Main challenges are appropriate sample preparation methods, reliable and validated quantification strategies and a trade-off between sensitivity and spatial resolution. So far, research has mostly focused on the development of analytical methods for imaging with the long term goal to study drug uptake into tumor tissue and toxicity affected organs and to identify cellular targets of metal-based drugs...
February 3, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28153232/optimization-and-evaluation-of-maldi-tof-mass-spectrometric-imaging-for-quantification-of-orally-dosed-octreotide-in-mouse-tissues
#20
Tai Rao, Boyu Shen, Zhangpei Zhu, Yuhao Shao, Dian Kang, Xinuo Li, Xiaoxi Yin, Haofeng Li, Lin Xie, Guangji Wang, Yan Liang
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) has received considerable attention in recent years since it allows molecular mapping of diverse bimolecular in animal/plant tissue sections, although some barriers still exist in absolute pixel-to-pixel quantification. Octreotide, a synthetic somatostatin analogue, has been widely used to prevent gastrointestine bleeding in the clinic. The aim of the present study is to develop a MALDI-TOF-MSI method for quantitatively visualizing spatial distribution of octreotide in mouse tissues...
April 1, 2017: Talanta
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