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https://www.readbyqxmd.com/read/28345958/macrophage-elastase-induces-trail-mediated-tumor-cell-death-through-its-carboxyterminal-domain
#1
Nadine Dandachi, Neil J Kelly, John P Wood, Christine L Burton, Josiah E Radder, Adriana S Leme, Alyssa D Gregory, Steven D Shapiro
RATIONALE: Macrophage elastase (MMP12) is a potent protease that contributes to the lung destruction that accompanies cigarette smoking while it simultaneously inhibits lung tumor angiogenesis and metastasis by catalyzing the formation of anti-angiogenic peptides. Recent studies have revealed novel non-proteolytic functions of MMP12, including antimicrobial activity through a peptide within its C-terminal domain (CTD). OBJECTIVES: Our objective was to determine whether the MMP12 CTD contributes to its anti-tumor activity in lung cancer...
March 27, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28345467/mitochondrial-dna-alteration-in-primary-and-metastatic-colorectal-cancer-different-frequency-and-association-with-selected-clinicopathological-and-molecular-markers
#2
Britta Kleist, Thuja Meurer, Micaela Poetsch
This study attempts to determine whether primary tumor tissue could reliably represent metastatic colorectal cancer in therapy-guiding analysis of mitochondrial microsatellite instability. Therefore, we investigated the concordance of microsatellite instability in D310, D514, and D16184 (mitochondrial DNA displacement loop), and its association with selected clinical categories and KRAS/NRAS/BRAF/PIK3CA/TP53 mutation status between primary and metastatic colorectal cancer tissue from 119 patients. Displacement loop microsatellite instability was significantly more frequently seen in lymph node metastases (53...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28343997/dna-double-strand-breaks-and-aurora-b-mislocalization-induced-by-exposure-of-early-mitotic-cells-to-h2o2-appear-to-increase-chromatin-bridges-and-resultant-cytokinesis-failure
#3
Min-Guk Cho, Ju-Hyun Ahn, Hee-Song Choi, Jae-Ho Lee
Aneuploidy, an abnormal number of chromosomes that is a hallmark of cancer cells, can arise from tetraploid/binucleated cells through a failure of cytokinesis. Reactive oxygen species (ROS) have been implicated in various diseases, including cancer. However, the nature and role of ROS in cytokinesis progression and related mechanisms has not been clearly elucidated. Here, using time-lapse analysis of asynchronously growing cells and immunocytochemical analyses of synchronized cells, we found that hydrogen peroxide (H2O2) treatment at early mitosis (primarily prometaphase) significantly induced cytokinesis failure...
March 24, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28342334/oncogene-addiction-in-non-small-cell-lung-cancer-focus-on-ros1-inhibition
#4
REVIEW
Francesco Facchinetti, Giulio Rossi, Emilio Bria, Jean-Charles Soria, Benjamin Besse, Roberta Minari, Luc Friboulet, Marcello Tiseo
Detection of molecular aberrations driving the biology and the clinical behavior of advanced non-small cell lung cancer (NSCLC) allows the adoption of specific therapeutic strategies dramatically impacting disease courses. Among these, ROS1 rearrangements are present in 1-2% of lung adenocarcinomas. Thanks to similarities between ALK and ROS1 oncogenes, lessons inferred from ALK can be applied to ROS1-positive NSCLC; nevertheless, disparities exist between diseases mastered by these two fusion genes. In the absence of more common genetic alterations detected in NSCLC (e...
March 12, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28339087/regulation-of-intestinal-myofibroblasts-by-kras-mutated-colorectal-cancer-cells-through-heparin-binding-epidermal-growth-factor-like-growth-factor
#5
Hideyoshi Kawasaki, Takuya Saotome, Tatsuya Usui, Takashi Ohama, Koichi Sato
In colorectal cancer, gain-of-function mutations in KRas play a critical role in malignant transformation. Tumor growth in colorectal cancer is known to be promoted by the intestinal myofibroblasts (IMFs) that localize adjacent to the cancer cells, but the mechanisms of interaction between KRas-mutated cancer cells and the myofibroblasts remain unclear. Here, we investigated the effects of KRas-mutated cells on the behavior of myofibroblasts by using mouse primary IMFs and cells of an IMF cell line (LmcMF) and a mouse colon epithelial cell line (aMoC1)...
March 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28339086/identification-of-novel-mutations-in-endometrial-cancer-patients-by-whole-exome-sequencing
#6
Ya-Sian Chang, Hsien-Da Huang, Kun-Tu Yeh, Jan-Gowth Chang
The aim of the present study was to identify genomic alterations in Taiwanese endometrial cancer patients. This information is vitally important in Taiwan, where endometrial cancer is the second most common gynecological cancer. We performed whole-exome sequencing on DNA from 14 tumor tissue samples from Taiwanese endometrial cancer patients. We used the Genome Analysis Tool kit software package for data analysis, and the dbSNP, Catalogue of Somatic Mutations in Cancer (COSMIC) and The Cancer Genome Atlas (TCGA) databases for comparisons...
March 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338535/lung-cancers-associated-with-cystic-airspaces-natural-history-pathologic-correlation-and-mutational-analysis
#7
Florian J Fintelmann, Jesaja K Brinkmann, William R Jeck, Fabian M Troschel, Subba R Digumarthy, Mari Mino-Kenudson, Jo-Anne O Shepard
PURPOSE: The aim of the study was to investigate the natural history of non-small cell lung cancers (NSCLCs) associated with cystic airspaces, including histopathology and molecular analysis. MATERIALS AND METHODS: A total of 34,801 computed tomographic (CT) scans of 2954 patients diagnosed with NSCLC between 2010 and 2015 were evaluated for association with a cystic airspace. Characteristics on serial CT, 18F-fludeoxyglucose positron emission tomography, and pathologic analysis were recorded...
March 22, 2017: Journal of Thoracic Imaging
https://www.readbyqxmd.com/read/28335073/clinical-characteristics-and-whole-exome-transcriptome-sequencing-of-coexisting-chronic-myeloid-leukemia-and-myelofibrosis
#8
Malathi Kandarpa, Yi-Mi Wu, Dan Robinson, Patrick William Burke, Arul M Chinnaiyan, Moshe Talpaz
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) disorders that can be classified on the basis of genetic, clinical, phenotypic features. Genetic lesions such as JAK2 mutations and BCR-ABL translocation are often mutually exclusive in MPN patients and lead to essential thrombocythemia, polycythemia vera or myelofibrosis (ET/PV/MF) or chronic myeloid leukemia, respectively. Nevertheless, coexistence of these genetic aberrations in the same patient has been reported. Whether these aberrations occur in the same stem cell or a different cell is unclear, but an unstable genome in the HSCs seems to be the common antecedent...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28333239/small-bowel-carcinomas-in-coeliac-or-crohn-s-disease-clinico-pathological-molecular-and-prognostic-features-a-study-from-the-small-bowel-cancer-italian-consortium
#9
Alessandro Vanoli, Antonio Di Sabatino, Daniela Furlan, Catherine Klersy, Federica Grillo, Roberto Fiocca, Claudia Mescoli, Massimo Rugge, Gabriella Nesi, Paolo Fociani, Gianluca Sampietro, Sandro Ardizzone, Ombretta Luinetti, Antonio Calabrò, Francesco Tonelli, Umberto Volta, Donatella Santini, Giacomo Caio, Paolo Giuffrida, Luca Elli, Stefano Ferrero, Giovanni Latella, Antonio Ciardi, Roberto Caronna, Gaspare Solina, Aroldo Rizzo, Carolina Ciacci, Francesco P D'Armiento, Marianna Salemme, Vincenzo Villanacci, Renato Cannizzaro, Vincenzo Canzonieri, Luca Reggiani Bonetti, Livia Biancone, Giovanni Monteleone, Augusto Orlandi, Giuseppe Santeusanio, Maria C Macciomei, Renata D'Incà, Vittorio Perfetti, Giancarlo Sandri, Marco Silano, Ada M Florena, Antonino G Giannone, Claudio Papi, Luigi Coppola, Paolo Usai, Antonio Maccioni, Marco Astegiano, Paola Migliora, Rachele Manca, Michele Martino, Davide Trapani, Roberta Cerutti, Paola Alberizzi, Roberta Riboni, Fausto Sessa, Marco Paulli, Enrico Solcia, Gino R Corazza
Background and Aims.: An increased risk of small bowel carcinoma (SBC) has been reported in coeliac disease (CD) and Crohn's disease (CrD). We explored clinico-pathologic, molecular and prognostic features of CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) in comparison with sporadic SBC (spo-SBC). Methods.: Seventy-six patients undergoing surgical resection for non-familial SBC (26 CD-SBC, 25 CrD-SBC, 25 spo-SBC) were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability (MSI) and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations...
February 24, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28332047/mechanisms-of-resistance-to-target-therapies-in-non-small-cell-lung-cancer
#10
Francesco Facchinetti, Claudia Proto, Roberta Minari, Marina Garassino, Marcello Tiseo
Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28331530/kras-detection-on-archival-cytological-smears-by-the-novel-fully-automated-polymerase-chain-reaction-based-idylla-mutation-test
#11
Caterina De Luca, Elena Vigliar, Melania d'Anna, Pasquale Pisapia, Claudio Bellevicine, Umberto Malapelle, Giancarlo Troncone
BACKGROUND: Molecular techniques are relevant to modern cytopathology, but their implementation is difficult without molecular expertise and infrastructure. The assessment of KRAS mutational status on cytological preparations may be useful either to refine uncertain diagnoses on pancreatic aspirates or to yield predictive information to plan targeted treatment of metastatic colorectal cancer (mCRC). The novel test Idylla™ enables fully automated KRAS genotyping in approximately 2 h, even in less experienced hands...
2017: CytoJournal
https://www.readbyqxmd.com/read/28330874/high-resolution-3d-nmr-structure-of-the-kras-proto-oncogene-promoter-reveals-key-features-of-a-g-quadruplex-involved-in-transcriptional-regulation
#12
Abdelaziz Kerkour, Julien Marquevielle, Stefaniia Ivashchenko, Liliya A Yatsunyk, Jean-Louis Mergny, Gilmar F Salgado
Non-canonical base pairing within guanine-rich DNA and RNA sequences can produce G-quartets, whose stacking leads to the formation of a G-quadruplex (G4). G4s can coexist with canonical duplex DNA in the human genome and have been suggested to suppress gene transcription, and much attention has therefore focused on studying G4s in promotor regions of disease-related genes. For example, the human KRAS proto-oncogene contains a nuclease-hypersensitive element (1) located upstream of the major transcription start site...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28329143/epidermal-growth-factor-receptor-mutations-are-linked-to-skip-n2-lymph-node-metastasis-in-resected-non-small-cell-lung-cancer-adenocarcinomas%C3%A2
#13
Francesco Guerrera, Stéphane Renaud, Fabrizio Tabbó, Anne-Claire Voegeli', Pier Luigi Filosso, Michèle Legrain, Monica Boita, Mickaël Schaeffer, Michèle Beau-Faller, Enrico Ruffini, Pierre-Emmanuel Falcoz, Giorgio Inghirami, Alberto Oliaro, Gilbert Massard
OBJECTIVES: The impact of skip N2 metastases (i.e. N2 lymph node metastases without N1) on survival in surgically resected non-small lung cancer remains an intriguing and rarely investigated topic. The goal of our study was to elucidate (i) skip N2 influence on overall survival (OS) and time to recurrence (TTR) in patients with resected lung adenocarcinoma and (ii) its link with epidermal growth factor receptor ( EGFR ) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations...
December 15, 2016: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28328959/kras-and-vegf-gene-3-utr-single-nucleotide-polymorphisms-predicted-susceptibility-in-colorectal-cancer
#14
Minnan Yang, Xiuli Xiao, Xiaorui Xing, Xin Li, Tian Xia, Hanan Long
Single nucleotide polymorphisms (SNPs) in tumor-related genes have been reported to play important roles in cancer development. Recent studies have shown that 3'-untranslated regions (UTR) polymorphisms are associated with the occurrence and prognosis of cancers. The aim of this study is to analyze the association between KRAS and VEGF gene 3'-UTR SNPs and genetic susceptibility to colorectal cancer (CRC). In this case-control study of 371 CRC cases and 246 healthy controls, we analyzed the association between one SNP (rs1137188G > A) in the KRAS gene and four SNPs (rs3025039C > T, rs3025040C > T, rs3025053G > A and rs10434A > G) in the VEGF gene and CRC susceptibility by the improved multiplex ligase detection reaction (iMLDR) method...
2017: PloS One
https://www.readbyqxmd.com/read/28328955/treatment-monitoring-in-metastatic-colorectal-cancer-patients-by-quantification-and-kras-genotyping-of-circulating-cell-free-dna
#15
Andreas W Berger, Daniel Schwerdel, Hanna Welz, Ralf Marienfeld, Stefan A Schmidt, Alexander Kleger, Thomas J Ettrich, Thomas Seufferlein
Treatment of metastatic colorectal cancer (CRC) has continuously improved over the last decade. However, disease monitoring remains underdeveloped and mostly dependent on imaging e.g. RECIST 1.1 criteria. The genetic landscape of individual cancers and subsequently occurring treatment-induced evolution remain neglected in current surveillance strategies. Novel biomarkers demand minimally invasive and repetitive tracking of the cancer mutagenome for therapy stratification and to make prognostic predictions. Carcinoembryonic antigen (CEA), a routinely used tumor marker for CRC, does not meet these goals and thus prevents its use as a reliable monitoring tool...
2017: PloS One
https://www.readbyqxmd.com/read/28328812/overall-survival-of-patients-with-kras-wild-type-tumor-treated-with-folfox-forfiri%C3%A2-cetuximab-as-the-first-line-treatment-for-metastatic-colorectal-cancer-a-meta-analysis
#16
Ya-Fan Yang, Gui-Ying Wang, Jing-Li He, Feng-Peng Wu, Yan-Ni Zhang
The addition of cetuximab to FOLFIRI or FOLFOX as the first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated systematic meta-analysis was undertaken to determine the efficacy of cetuximab plus FOLFIRI or FOLFOX.Major databases were searched to identify RCTs investigating wild-type KRAS mCRC after the first-line treatment, and treatment with FOLFOX/FORFIRI ± cetuximab was compared...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28327928/detecting-mutant-kras-in-liquid-biopsies-a-biomarker-searching-for-a-role
#17
Zoltan Szallasi
No abstract text is available yet for this article.
March 6, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327908/predicted-vitamin-d-status-and-colon-cancer-recurrence-and-mortality-in-calgb-89803-alliance
#18
M A Fuchs, C Yuan, K Sato, D Niedzwiecki, X Ye, L B Saltz, R J Mayer, R B Mowat, R Whittom, A Hantel, A Benson, D Atienza, M Messino, H Kindler, A Venook, F Innocenti, R S Warren, M M Bertagnolli, S Ogino, E L Giovannucci, E Horvath, J A Meyerhardt, K Ng
Background: HASH(0x4a5f708) Observational studies suggest that higher levels of 25-hydroxyvitamin D 3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. Patients and methods: HASH(0x4a50db0) We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1,016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803)...
March 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28326956/clinical-pathologic-and-genetic-features-of-wilms-tumors-with-wtx-gene-mutation
#19
Sanda Alexandrescu, Sara Akhavanfard, Marian H Harris, Sara O Vargas
Clinical and pathologic features of patients with WTX-mutated Wilms tumor (WT) have not been studied in detail. We characterize the clinical and pathologic findings in WT with WTX abnormalities and provide comparison with WT without WTX mutation. Clinical, gross, and microscopic features in 35 patients with WT were examined. Karyotype was examined in a subset of cases. All cases had been previously analyzed for WTX, WT1, and CTNNB1 aberrations via array comparative genomic hybridization; OncoMap 4 high throughput genotyping was performed on 18 cases...
March 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28325827/sessile-serrated-polyps-and-colon-cancer-prevention
#20
Shahrooz Rashtak, Rafaela Rego, Seth R Sweetser, Frank A Sinicrope
Evidence suggests that up to one fifth of colorectal carcinomas (CRC) develop from serrated polyps, named for their pattern of colonic crypts, and include the sessile serrated adenoma/polyp (SSA/P) that has malignant potential. SSA/Ps are typically located in the proximal colon and have molecular features of hypermethylation of CpG islands in gene promoters and activating point mutations (V600E) in the BRAF oncogene. Both of these features are seen in sporadic CRCs with microsatellite instability (MSI) which is potentially consistent with an origin of these cancers from precursor SSA/Ps...
March 21, 2017: Cancer Prevention Research
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