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https://www.readbyqxmd.com/read/29344557/in-colonic-%C3%AF-0-rho0-cells-reduced-mitochondrial-function-mediates-transcriptomic-alterations-associated-with-cancer
#1
Harrison M Penrose, Sandra Heller, Chloe Cable, Hani Nakhoul, Nate Ungerleider, Melody Baddoo, Zachary F Pursell, Erik K Flemington, Susan E Crawford, Suzana D Savkovic
Background: Mitochondrial reprogramming has emerged as a hallmark of cancer pathobiology. Although it is believed this reprogramming is essential for cancer cells to thrive, how it supports cancer pathobiology is unclear. We previously generated colonic ρ0 (rho0) cells with reduced mitochondrial energy function and acquired their transcriptional signature. Here, we utilized a bioinformatics approach to identify their changes linked to cancer pathobiology. Methods: Human colon cancer HCT116 cells, control and ρ0, were used for qPCR...
November 2017: Oncoscience
https://www.readbyqxmd.com/read/29341160/genetic-analysis-of-surgical-margins-in-oral-cavity-cancer
#2
S A Liu, C C Wang, R S Jiang, W Y Wang, J C Lin
BACKGROUND: A histological, tumour-free surgical margin does not guarantee recurrence-free survival in patients with cancer. This study investigated the association between microsatellite alteration in tumour-free surgical margins and local recurrence in patients with oral cavity squamous cell carcinoma. METHODS: Patients with histologically confirmed oral cavity squamous cell carcinoma were enrolled in this prospective study. Cancerous specimens, corresponding surgical margins and peripheral blood were obtained...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29340115/hypermutation-and-microsatellite-instability-in-gastrointestinal-cancers
#3
REVIEW
Kizuki Yuza, Masayuki Nagahashi, Satoshi Watanabe, Kazuaki Takabe, Toshifumi Wakai
Recent progress in cancer genome analysis using next-generation sequencing has revealed a high mutation burden in some tumors. The particularly high rate of somatic mutation in these tumors correlates with the generation of neo-antigens capable of eliciting an immune response. Identification of hypermutated tumors is therefore clinically valuable for selecting patients suitable for immunotherapy treatment. There are several known causes of hypermutation in tumors, such as ultraviolet light in melanoma, tobacco smoke in lung cancer, and excessive APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) activity in breast and gastric cancer...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29334683/epigenetic-silencing-of-the-mlh1-promoter-in-relation-to-the-development-of-gastric-cancer-and-its-use-as-a-biomarker-for-patients-with-microsatellite-instability-a-systematic-analysis
#4
Guimei Hu, Lijun Qin, Xinjun Zhang, Guoliang Ye, Tao Huang
BACKGROUND/AIMS: Human mutL homolog 1 (MLH1) promoter methylation was reported in gastric cancer (GC). This study determined the clinicopathological, prognostic, and diagnostic effects of MLH1 promoter methylation in GC. METHODS: The combined odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence intervals (95% CI) were calculated. The pooled sensitivity, specificity, and area under the curve (AUC) were analyzed. RESULTS: A total of 4654 GC patients and 3669 non-malignant controls were identified in this systematic analysis...
January 15, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29329588/accuracy-of-four-mononucleotide-repeat-markers-for-the-identification-of-dna-mismatch-repair-deficiency-in-solid-tumors
#5
Yuko Takehara, Takeshi Nagasaka, Akihiro Nyuya, Tomoko Haruma, Junko Haraga, Yoshiko Mori, Keiichiro Nakamura, Toshiyoshi Fujiwara, C Richard Boland, Ajay Goel
BACKGROUND: To screen tumors with microsatellite instability (MSI) arising due to DNA mismatch repair deficiency (dMMR), a panel of five quasi-monomorphic mononucleotide-repeat markers amplified in a multiplex PCR (Pentaplex) are commonly used. In spite of its several strengths, the pentaplex assay is not robust at detecting the loss of MSH6-deficiency (dMSH6). In order to overcome this challenge, we designed this study to develop and optimize a panel of four quasi-monomorphic mononucleotide-repeat markers (Tetraplex) for identifying solid tumors with dMMR, especially dMSH6...
January 12, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29329208/advances-in-molecular-profiling-and-categorisation-of-pancreatic-adenocarcinoma-and-the-implications-for-therapy
#6
REVIEW
Rille Pihlak, Jamie M J Weaver, Juan W Valle, Mairéad G McNamara
Pancreatic ductal adenocarcinoma (PDAC) continues to be a disease with poor outcomes and short-lived treatment responses. New information is emerging from genome sequencing identifying potential subgroups based on somatic and germline mutations. A variety of different mutations and mutational signatures have been identified; the driver mutation in around 93% of PDAC is KRAS, with other recorded alterations being SMAD4 and CDKN2A. Mutations in the deoxyribonucleic acid (DNA) damage repair pathway have also been investigated in PDAC and multiple clinical trials are ongoing with DNA-damaging agents...
January 12, 2018: Cancers
https://www.readbyqxmd.com/read/29327160/differences-in-histological-features-and-pd-l1-expression-between-sporadic-microsatellite-instability-and-lynch-syndrome-associated-disease-in-japanese-patients-with-colorectal-cancer
#7
Rin Yamada, Tatsuro Yamaguchi, Takeru Iijima, Rika Wakaume, Misato Takao, Koichi Koizumi, Tsunekazu Hishima, Shin-Ichiro Horiguchi
BACKGROUND: The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. METHODS: Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis...
January 11, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29321555/fourier-transform-infrared-microscopy-enables-guidance-of-automated-mass-spectrometry-imaging-to-predefined-tissue-morphologies
#8
Jan-Hinrich Rabe, Denis A Sammour, Sandra Schulz, Bogdan Munteanu, Martina Ott, Katharina Ochs, Peter Hohenberger, Alexander Marx, Michael Platten, Christiane A Opitz, Daniel S Ory, Carsten Hopf
Multimodal imaging combines complementary platforms for spatially resolved tissue analysis that are poised for application in life science and personalized medicine. Unlike established clinical in vivo multimodality imaging, automated workflows for in-depth multimodal molecular ex vivo tissue analysis that combine the speed and ease of spectroscopic imaging with molecular details provided by mass spectrometry imaging (MSI) are lagging behind. Here, we present an integrated approach that utilizes non-destructive Fourier transform infrared (FTIR) microscopy and matrix assisted laser desorption/ionization (MALDI) MSI for analysing single-slide tissue specimen...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320758/polymerase-epsilon-mutations-and-concomitant-%C3%AE-2-microglobulin-mutations-in-cancer
#9
Ioannis A Voutsadakis
Mutations in the exonuclease domain of polymerase epsilon (POLE), an enzyme of DNA synthesis, are involved in a newly described syndrome of colorectal polyposis and cancer, and have been associated with a high mutation burden with or without microsatellite instability (MSI) phenotype. The exonuclease domain of POLE executes a proofreading function that decreases the mutation rate during DNA replication by an estimated of one to two orders. The high mutation burden resulting from its loss of function could create a load of neo-antigens that would put the neoplastic cells in severe disadvantage of an immune attack if properly presented to the immune system...
January 7, 2018: Gene
https://www.readbyqxmd.com/read/29315936/biosynthesis-of-bioactive-diterpenoids-in-the-medicinal-plant-vitex-agnus-castus
#10
Allison Maree Heskes, Tamil C M Sundram, Berin Alain Boughton, Niels Bjerg Jensen, Nikolaj Lervad Hansen, Christoph Crocoll, Federico Cozzi, Simon Rasmussen, Britta Hamberger, Björn Hamberger, Dan Staerk, Birger Lindberg Møller, Irini Pateraki
Vitex agnus-castus L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ability to lower prolactin levels. This feature has been attributed to the presence of dopaminergic diterpenoids that can bind to dopamine receptors in the pituitary gland. Phytochemical analyses of V. agnus-castus show that it contains an enormous array of structurally related diterpenoids and, as such holds potential as a rich source of new dopaminergic drugs...
January 8, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29310285/silver-nanoparticles-as-matrix-for-maldi-fticr-ms-profiling-and-imaging-of-diverse-lipids-in-brain
#11
Ming Guan, Zhen Zhang, Shilei Li, Jian'an Liu, Lu Liu, Hui Yang, Yangyang Zhang, Tie Wang, Zhenwen Zhao
Owing to the diversity of lipids, profiling and imaging multiple classes of lipids in one analysis by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) is a great challenge. In this work, polyvinylpyrrolidone (PVP) capped silver nanoparticles (AgNPs) was used as the matrix for MALDI MSI for the first time to simultaneously analyze 10 classes of lipids from the brain. This analysis included fatty acids and their derivatives, sterols, CPAs, LPA and PAs, LPE and PEs, LPC and PCs, PS, Cers, SMs, and MAGs and DAGs, and other small metabolites...
March 1, 2018: Talanta
https://www.readbyqxmd.com/read/29310227/quantitative-analysis-of-drug-distribution-by-ambient-mass-spectrometry-imaging-method-with-signal-extinction-normalization-strategy-and-inkjet-printing-technology
#12
Zhigang Luo, Jingjing He, Jiuming He, Lan Huang, Xiaowei Song, Xin Li, Zeper Abliz
Quantitative mass spectrometry imaging (MSI) is a robust approach that provides both quantitative and spatial information for drug candidates' research. However, because of complicated signal suppression and interference, acquiring accurate quantitative information from MSI data remains a challenge, especially for whole-body tissue sample. Ambient MSI techniques using spray-based ionization appear to be ideal for pharmaceutical quantitative MSI analysis. However, it is more challenging, as it involves almost no sample preparation and is more susceptible to ion suppression/enhancement...
March 1, 2018: Talanta
https://www.readbyqxmd.com/read/29308475/tpaoh-assisted-size-tunable-gd2o3-msi-core-shell-nanostructures-for-multifunctional-biomedical-applications
#13
E Pavitra, G Seeta Rama Raju, Ganji Purnachandra Nagaraju, Goli Nagaraju, Young-Kyu Han, Yun Suk Huh, Jae Su Yu
We report a facile and large-scale synthesis of size-tunable and nontoxic mesoporous silica-coated Gd2O3:Eu3+ (Gd@mSi) core-shell nanostructures using a TPAOH assisted modified UHP technique. The role of TPAOH in controlling the particle size was evaluated. The potentiality of these Gd@mSi core-shell nanoparticles before and after folic acid conjugation was established by in vitro fluorescence microscopy of the U2OS cell lines for cancer imaging and therapy.
January 8, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29308317/high-numbers-of-pdcd1-pd-1-positive-t-cells-and-b2m-mutations-in-microsatellite-unstable-colorectal-cancer
#14
Jonas Janikovits, Meike Müller, Julia Krzykalla, Sandrina Körner, Fabian Echterdiek, Bernd Lahrmann, Niels Grabe, Martin Schneider, Axel Benner, Magnus von Knebel Doeberitz, Matthias Kloor
DNA mismatch repair (MMR)-deficient cancers accumulate high numbers of coding microsatellite mutations, which lead to the generation of highly immunogenic frameshift peptide (FSP) neoantigens. MMR-deficient cells can grow out to clinically manifest cancers either if they evade immune cell attack or if local T-cells get exhausted. Therefore, a subset of MSI cancer patients responds particularly well to treatment with immune checkpoint inhibitors. We analyzed whether immune evasion in MMR-deficient cancer mediated by loss of HLA class I or II antigens is related to local immune cell activation status...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29307833/analysis-of-spatiotemporal-metabolomic-dynamics-for-sensitively-monitoring-biological-alterations-in-cisplatin-induced-acute-kidney-injury
#15
Miho Irie, Eisuke Hayakawa, Yoshinori Fujimura, Youhei Honda, Daiki Setoyama, Hiroyuki Wariishi, Fuminori Hyodo, Daisuke Miura
Clinical application of the major anticancer drug, cisplatin, is limited by severe side effects, especially acute kidney injury (AKI) caused by nephrotoxicity. The detailed metabolic mechanism is still largely unknown. Here, we used an integrated technique combining mass spectrometry imaging (MSI) and liquid chromatography-mass spectrometry (LC-MS) to visualize the diverse spatiotemporal metabolic dynamics in the mouse kidney after cisplatin dosing. Biological responses to cisplatin was more sensitively detected within 24 h as a metabolic alteration, which is much earlier than possible with the conventional clinical chemistry method of blood urea nitrogen (BUN) measurement...
January 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29305797/anatomical-molecular-distribution-of-ephrina1-in-infarcted-mouse-heart-using-maldi-mass-spectrometry-imaging
#16
Stephan Lefcoski, Kimberly Kew, Shaun Reece, Maria J Torres, Justin Parks, Sky Reece, Lisandra E de Castro Brás, Jitka A I Virag
EphrinA1 is a tyrosine kinase receptor localized in the cellular membrane of healthy cardiomyocytes, the expression of which is lost upon myocardial infarction (MI). Intra-cardiac injection of the recombinant form of ephrinA1 (ephrinA1-Fc) at the time of ligation in mice has shown beneficial effects by reducing infarct size and myocardial necrosis post-MI. To date, immunohistochemistry and Western blotting comprise the only experimental approaches utilized to localize and quantify relative changes of ephrinA1 in sections and homogenates of whole left ventricle, respectively...
January 5, 2018: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/29305587/consensus-molecular-subtypes-of-colorectal-cancer-are-recapitulated-in-in-vitro-and-in-vivo-models
#17
Janneke F Linnekamp, Sander R van Hooff, Pramudita R Prasetyanti, Raju Kandimalla, Joyce Y Buikhuisen, Evelyn Fessler, Prashanthi Ramesh, Kelly A S T Lee, Grehor G W Bochove, Johan H de Jong, Kate Cameron, Ronald van Leersum, Hans M Rodermond, Marek Franitza, Peter Nürnberg, Laura R Mangiapane, Xin Wang, Hans Clevers, Louis Vermeulen, Giorgio Stassi, Jan Paul Medema
Colorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called consensus molecular subtypes (CMS1-4), each of which has a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed...
January 5, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29303062/the-role-of-microsatellite-instability-in-positive-margin-gastric-cancer-patients
#18
Karol Polom, Daniele Marrelli, Elizabeth C Smyth, Costantino Voglino, Giandomenico Roviello, Valeria Pascale, Julian Varas, Carla Vindigni, Franco Roviello
PURPOSE: A positive resection margin (RM+) is acknowledged as a poor prognostic factor after gastrectomy. Microsatellite instability (MSI-H) gastric cancer has been identified as a subgroup of gastric cancer that may be associated with an improved prognosis. The aim of the study was an analysis of MSI status on patients with margin involvement after gastrectomy and examination of the association between MSI, margin status, and survival outcomes. METHODS: From a large prospectively annotated surgical database we collected clinicopathological and survival data on patients who had undergone a potentially curative resection for gastric cancer...
January 1, 2018: Surgical Innovation
https://www.readbyqxmd.com/read/29297598/visualization-of-the-distribution-of-anthocyanin-species-in-mice-eyeball-by-maldi-mass-spectrometry-imaging
#19
Shuhei Yamada, Nobuhiro Zaima, Yukihiro Yoshimura, Shiori Inaba, Takamichi Fujimori, Tetsuya Sogon, Tatsuya Moriyama
RATIONALE: Anthocyanins, which belong to a class of molecules called flavonoids, are known to have beneficial effects for both humans and animals. Many physiological functions have been attributed to anthocyanins since ancient times. The most important function is the relief of eyestrain, but the biodistribution of anthocyanins remains unknown. In this study, we analyzed the kinetics of anthocyanin species in mice eyeballs and surrounding tissues. METHODS: We used mice that were administered bilberry extract solution intraperitoneally...
January 3, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29295753/differentiation-between-malignant-and-benign-breast-masses-combination-of-semi-quantitative-analysis-on-dce-mri-and-histogram-analysis-of-adc-maps
#20
H-L Liu, M Zong, H Wei, J-J Lou, S-Q Wang, Q-G Zou, H-B Shi, Y-N Jiang
AIM: To investigate the performance of combined semi-quantitative analysis on dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and histogram analysis of diffusion-weighted imaging (DWI) for distinguishing malignant from benign breast masses. MATERIALS AND METHODS: This study included 178 patients with breast masses (benign:malignant=88:9) who underwent both DCE-MRI and DWI. The semi-quantitative parameters, derived from DCE-MRI, included maximum slope of increase (MSI), signal intensity slope (SIslope), initial percentage of enhancement (Einitial), percentage of peak enhancement (Epeak), early signal enhancement ratio (ESER), and second enhancement percentage (SEP)...
December 30, 2017: Clinical Radiology
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