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https://www.readbyqxmd.com/read/29333122/metformin-enhanced-in-vitro-radiosensitivity-associates-with-g2-m-cell-cycle-arrest-and-elevated-adenosine-5-monophosphate-activated-protein-kinase-levels-in-glioblastoma
#1
Sebastian Adeberg, Denise Bernhardt, Semi B Harrabi, Nils H Nicolay, Juliane Hörner-Rieber, Laila König, Michael Repka, Angela Mohr, Amir Abdollahi, Klaus-Josef Weber, Juergen Debus, Stefan Rieken
Background: It is hypothesized that metabolism plays a strong role in cancer cell regulation. We have recently demonstrated improved progression-free survival in patients with glioblastoma who received metformin as an antidiabetic substance during chemoradiation. Although metformin is well-established in clinical use the influence of metformin in glioblastoma is far from being understood especially in combination with other treatment modalities such as radiation and temozolomide. Materials and Methods: In this study, we examined the influence of metformin in combinations with radiation and temozolomide on cell survival (clonogenic survival), cell cycle (routine flow cytometric analysis, FACScan), and phosphorylated Adenosine-5'-monophosphate-activated protein kinase (AMPK) (Phopho-AMPKalpha1 - ELISA) levels in glioblastoma cell lines LN18 and LN229...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29331492/prognostic-value-of-the-expression-of-dna-repair-related-biomarkers-mediated-by-alcohol-in-gastric-cancer-patients
#2
Yiyin Zhang, Hongyang Wu, Feng Yang, Jie Ning, Min Li, Chenchen Zhao, Shuping Zhong, Kangsheng Gu, Hua Wang
Alcohol consumption likely induces gastric carcinogenesis through deregulation of RNA polymerase (Pol) III genes and oxidative damage. Transcription factor IIB-related factor 1 (BRF1) overexpression alleviates RNA Pol III transcription inhibition through breast cancer susceptibility gene 1 (BRCA1). Myeloperoxidase (MPO) involvement in cancer is induced by alcohol-mediated oxidative damage. BRCA1/2 and MPO play key roles in DNA repair. BRCA1 and BRCA2 exert different roles in homologous recombination repair...
January 5, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29330943/epigenetic-markers-in-circulating-cell-free-dna-as-prognostic-markers-for-survival-of-castration-resistant-prostate-cancer-patients
#3
Rianne J Hendriks, Siebren Dijkstra, Frank P Smit, Johan Vandersmissen, Hendrik Van de Voorde, Peter F A Mulders, Inge M van Oort, Wim Van Criekinge, Jack A Schalken
BACKGROUND: Noninvasive biomarkers to guide personalized treatment for castration-resistant prostate cancer (CRPC) are needed. In this study, we analyzed hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA (cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA concentrations and levels of the epigenetic markers and to assess the value of these biomarkers for prognosis. METHODS: In this prospective study, patients were included before starting new treatment after developing CRPC...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29330557/linear-doggybone-dna-vaccine-induces-similar-immunological-responses-to-conventional-plasmid-dna-independently-of-immune-recognition-by-tlr9-in-a-pre-clinical-model
#4
Alex Allen, Chuan Wang, Lisa J Caproni, Gessa Sugiyarto, Elena Harden, Leon R Douglas, Patrick J Duriez, Kinga Karbowniczek, Jon Extance, Paul J Rothwell, Ifeayinwa Orefo, John P Tite, Freda K Stevenson, Christian H Ottensmeier, Natalia Savelyeva
Vaccination with DNA that encodes cancer antigens is a simple and convenient way to raise immunity against cancer and has already shown promise in the clinical setting. Conventional plasmid DNA is commonly used which together with the encoded antigen also includes bacterial immunostimulatory CpG motifs to target the DNA sensor Toll-like receptor 9. Recently DNA vaccines using doggybone DNA (dbDNA™), have been developed without the use of bacteria. The cell-free process relies on the use of Phi29 DNA polymerase to amplify the template followed by protelomerase TelN to complete individual closed linear DNA...
January 12, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29330288/epigenetically-regulated-chromosome-14q32-mirna-cluster-induces-metastasis-and-predicts-poor-prognosis-in-lung-adenocarcinoma-patients
#5
Margarita Gonzalez-Vallinas, Manuel Rodriguez-Paredes, Marco Albrecht, Carsten Sticht, Damian Stichel, Julian Gutekunst, Adriana Pitea, Steffen Sass, Francisco J Sánchez-Rivera, Justo L Bermejo, Jennifer Schmitt, Carolina De La Torre, Arne Warth, Fabian Theis, Nikola Mueller, Norbert Gretz, Thomas Muley, Michael Meister, Darjus F Tschaharganeh, Peter Schirmacher, Franziska Matthäus, Kai Breuhahn
Most lung cancer deaths are related to metastases, which indicates the necessity of detecting and inhibiting tumor cell dissemination. Here, we aimed to identify microRNAs (miRNAs) involved in metastasis of lung adenocarcinoma as prognostic biomarkers and therapeutic targets. To that end, lymph node metastasis-associated miRNAs were identified in The Cancer Genome Atlas (TCGA) lung adenocarcinoma patient cohort (sequencing data; n=449) and subsequently validated by RT-qPCR in an independent clinical cohort (n=108)...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330207/early-assessment-of-lung-cancer-immunotherapy-response-via-circulating-tumor-dna
#6
Sarah B Goldberg, Azeet Narayan, Adam J Kole, Roy H Decker, Jimmitti Teysir, Nicholas J Carriero, Angela Lee, Roxanne Nemati, Sameer K Nath, Shrikant M Mane, Yanhong Deng, Nitin Sukumar, Daniel Zelterman, Daniel J Boffa, Katerina Politi, Scott Gettinger, Lynn D Wilson, Roy S Herbst, Abhijit A Patel
PURPOSE: Decisions to continue or suspend therapy with immune checkpoint inhibitors are commonly guided by tumor dynamics seen on serial imaging.  However, immunotherapy responses are uniquely challenging to interpret because tumors often shrink slowly or can appear transiently enlarged due to inflammation.  We hypothesized that monitoring tumor cell death in real-time by quantifying changes in circulating tumor DNA (ctDNA) levels could enable early assessment of immunotherapy efficacy...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29326285/prevalence-of-aflatoxin-associated-tp53r249s-mutation-in-hepatocellular-carcinoma-in-hispanics-in-south-texas
#7
Jingjing Jiao, Weibo Niu, Ying Wang, Keith Baggerly, Yuanqing Ye, Xifeng Wu, Dewitt Davenport, Jose Luis Almeda, Monica M Betancourt-Garcia, R Armour Forse, Heather L Stevenson, Gordon P Watt, Joseph B McCormick, Susan P Fisher-Hoch, Laura Beretta
We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas. We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and RFLP. TP53R249S mutation was detected in 3 of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell-free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas...
January 11, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29326054/size-based-separation-methods-of-circulating-tumor-cells
#8
Si-Jie Hao, Yuan Wan, Yi-Qiu Xia, Xin Zou, Si-Yang Zheng
Circulating tumor cells (CTCs) originate from the primary tumor mass and enter into the peripheral bloodstream. Compared to other "liquid biopsy" portfolios such as exosome, circulating tumor DNA/RNA (ctDNA/RNA), CTCs have incomparable advantages in analyses of transcriptomics, proteomics, and signal colocalization. Hence, CTCs hold the key to understanding the biology of metastasis and play a vital role in cancer diagnosis, treatment monitoring, and prognosis. Size-based enrichment featureS prominently in CTC isolation...
January 8, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29325226/citrullinated-histone-h3-a-biomarker-of-neutrophil-extracellular-trap-formation-predicts-the-risk-of-venous-thromboembolism-in-cancer-patients
#9
Lisa-Marie Mauracher, Florian Posch, Kimberly Martinod, Ella Grilz, Thomas Däullary, Lena Hell, Christine Brostjan, Christoph Zielinski, Cihan Ay, Denisa D Wagner, Ingrid Pabinger, Johannes Thaler
BACKGROUND: Neutrophil extracellular traps (NETs) are decondensed chromatin fibers which might play a role in the prothrombotic state of cancer patients. OBJECTIVES: Here we investigated whether citrullinated histone H3 (H3Cit), a biomarker for NET formation, cell-free DNA (cfDNA), and nucleosomes predict venous thromboembolism (VTE) in cancer patients. PATIENTS/METHODS: Nine-hundred-forty-six patients with newly-diagnosed cancer or progression after remission were enrolled in this prospective observational cohort study...
January 11, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29325035/amplicon-based-next-generation-sequencing-of-plasma-cell-free-dna-for-detection-of-driver-and-resistance-mutations-in-advanced-non-small-cell-lung-cancer
#10
N Guibert, Y Hu, N Feeney, Y Kuang, V Plagnol, G Jones, K Howarth, J F Beeler, C P Paweletz, G R Oxnard
Background: Genomic analysis of plasma cell-free DNA is transforming lung cancer care, however available assays are limited by cost, turnaround time, and imperfect accuracy. Here we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC). Methods: Plasma samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1 and other rare genotypes) were collected while on therapy and analyzed, blinded to tumor genotype...
January 9, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29317345/muc1-aptamer-targeted-dna-micelles-for-dual-tumor-therapy-using-doxorubicin-and-kla-peptide
#11
Fahimeh Charbgoo, Mona Alibolandi, Seyed Mohammad Taghdisi, Khalil Abnous, Fatemeh Soltani, Mohammad Ramezani
Targeted delivery of DNA nanoparticles is a promising approach in cancer therapy. Using aptamers, target specific delivery of DNA nanoparticles can be achieved. Further, aptamers can indirectly improve drug encapsulation efficiency of DNA nanoparticles for drugs intercalated within nucleic acid base pairs. Using DNA blocks, a micellar hybrid nanoparticle was prepared for the targeted co-delivery of doxorubicin and a pro-apoptotic peptide, KLA to tumor cells. Results demonstrated that anti-MUC1 aptamer could specifically deliver the synthesized DNA micelle into MCF-7 cells by improving its cellular uptake...
January 6, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29310422/anti-proliferative-activities-of-vasicinone-on-lung-carcinoma-cells-mediated-via-activation-of-both-mitochondria-dependent-and-independent-pathways
#12
Tapan Dey, Prachurjya Dutta, Prasenjit Manna, Jatin Kalita, Hari Prasanna Deka Boruah, Alak Kumar Buragohain, Balagopalan Unni
Vasicinone, a quinazoline alkaloid from Adhatoda vasica Nees. is well known for its bronchodilator activity. However its anti-proliferative activities is yet to be elucidated. Here-in we investigated the anti-proliferative effect of vasicinone and its underlying mechanism against A549 lung carcinoma cells. The A549 cells upon treatment with various doses of vasicinone (10, 30, 50, 70 μM) for 72 h showed significant decrease in cell viability. Vasicinone treatment also showed DNA fragmentation, LDH leakage, and disruption of mitochondrial potential, and lower wound healing ability in A549 cells...
January 9, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29310244/a-dual-targeting-dna-tetrahedron-nanocarrier-for-breast-cancer-cell-imaging-and-drug-delivery
#13
Xiaoting Liu, Lina Wu, Lei Wang, Wei Jiang
To enhance efficacy of chemotherapy and achieve real-time imaging of cancer cells, it is crucial to develop nanocarriers with targeted drug delivery capacity and fluorescence property for cancer theranostics. Herein, a dual-targeting DNA tetrahedron nanocarrier (MUC1-Td-AS1411) was constructed for breast cancer cell imaging and targeted drug delivery. This nanocarrier consisted of three components: (i) DNA tetrahedron core for multivalent conjugation of function ligands and loading doxorubicin (Dox); (ii) activatable MUC1 aptamer probe (MUC1-probe), formed by the hybridization of MUC1 aptamer sequence with fluorophore extended from one vertex and complementary sequence with quencher, for targeting and imaging MUC1 protein on cytomembrane; (iii) AS1411 aptamer, which was hybridized to the overhang on three vertexes via prolonged sequence, for binding to nucleolin...
March 1, 2018: Talanta
https://www.readbyqxmd.com/read/29306943/clinically-observed-estrogen-receptor-alpha-mutations-within-the-ligand-binding-domain-confer-distinguishable-phenotypes
#14
Shanhang Jia, Mark T Miedel, Marilyn Ngo, Ryan Hessenius, Ning Chen, Peilu Wang, Amir Bahreini, Zheqi Li, Zhijie Ding, Tong Ying Shun, Daniel M Zuckerman, D Lansing Taylor, Shannon L Puhalla, Adrian V Lee, Steffi Oesterreich, Andrew M Stern
OBJECTIVE: Twenty to fifty percent of estrogen receptor-positive (ER+) metastatic breast cancers express mutations within the ER ligand-binding domain. While most studies focused on the constitutive ER signaling activity commonly engendered by these mutations selected during estrogen deprivation therapy, our study was aimed at investigating distinctive phenotypes conferred by different mutations within this class. METHODS: We examined the two most prevalent mutations, D538G and Y537S, employing corroborative genome-edited and lentiviral-transduced ER+ T47D cell models...
January 6, 2018: Oncology
https://www.readbyqxmd.com/read/29306909/detection-of-egfr-kras-and-braf-mutations-in-metastatic-cells-from-cerebrospinal-fluid
#15
Diane Frankel, Isabelle Nanni-Metellus, Andrée Robaglia-Schlupp, Pascale Tomasini, Julien Guinde, Fabrice Barlesi, Philippe Astoul, L'Houcine Ouafik, Florent Amatore, Véronique Secq, Elise Kaspi, Patrice Roll
BACKGROUND: In lung adenocarcinoma, molecular profiling of actionable genes has become essential to set up targeted therapies. However, the feasibility and the relevance of molecular profiling from the cerebrospinal fluid (CSF) in the context of meningeal metastasis have been poorly assessed. METHODS: We selected patients with stage IV lung adenocarcinoma harbouring metastatic cells in the CSF after cytological analysis. Seven samples from six patients were eligible for molecular testing of epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS), v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) and human epidermal growth factor receptor 2 (HER2) mutations using quantitative polymerase chain reaction (PCR) high-resolution melting curve analysis and Sanger sequencing after DNA extraction from the cell pellets of the CSF...
January 8, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29299160/detection-of-prognostic-methylation-markers-by-methylc-capture-sequencing-in-acute-myeloid-leukemia
#16
Yan Li, Hongmei Zhao, Qingyu Xu, Na Lv, Yu Jing, Lili Wang, Xiaowen Wang, Jing Guo, Lei Zhou, Jing Liu, Guofeng Chen, Chongjian Chen, Yonghui Li, Li Yu
Clinical and genetic features incompletely predict outcome in acute myeloid leukemia (AML). The value of clinical methylation assays for prognostic markers has not been extensively explored. We assess the prognostic implications of methylC-capture sequencing (MCC-Seq) in patients with de novo AML by integrating DNA methylation and genetic risk stratification. MCC-Seq assessed DNA methylation level in 44 samples. The differentially methylated regions associated with prognostic genetic information were identified...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298117/association-of-cell-free-dna-tumor-fraction-and-somatic-copy-number-alterations-with-survival-in-metastatic-triple-negative-breast-cancer
#17
Daniel G Stover, Heather A Parsons, Gavin Ha, Samuel S Freeman, William T Barry, Hao Guo, Atish D Choudhury, Gregory Gydush, Sarah C Reed, Justin Rhoades, Denisse Rotem, Melissa E Hughes, Deborah A Dillon, Ann H Partridge, Nikhil Wagle, Ian E Krop, Gad Getz, Todd R Golub, J Christopher Love, Eric P Winer, Sara M Tolaney, Nancy U Lin, Viktor A Adalsteinsson
Purpose Cell-free DNA (cfDNA) offers the potential for minimally invasive genome-wide profiling of tumor alterations without tumor biopsy and may be associated with patient prognosis. Triple-negative breast cancer (TNBC) is characterized by few mutations but extensive somatic copy number alterations (SCNAs), yet little is known regarding SCNAs in metastatic TNBC. We sought to evaluate SCNAs in metastatic TNBC exclusively via cfDNA and determine if cfDNA tumor fraction is associated with overall survival in metastatic TNBC...
January 3, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29290998/detection-of-somatic-variants-and-egfr-mutations-in-cell-free-dna-from-non-small-cell-lung-cancer-patients-by-ultra-deep-sequencing-using-the-ion-ampliseq-cancer-hotspot-panel-and-droplet-digital-polymerase-chain-reaction
#18
Jae Sook Sung, Hyon Yong Chong, Nak-Jung Kwon, Hae Mi Kim, Jong Won Lee, Boyeon Kim, Saet Byeol Lee, Chang Won Park, Jung Yoon Choi, Won Jin Chang, Yoon Ji Choi, Sung Yong Lee, Eun Joo Kang, Kyong Hwa Park, Yeul Hong Kim
Highly sensitive genotyping assays can detect mutations in cell-free DNA (cfDNA) from cancer patients, reflecting the biology of each patient's cancer. Because circulating tumor DNA comprises a small, variable fraction of DNA circulating in the blood, sensitive parallel multiplexing tests are required to determine mutation profiles. We prospectively examined the clinical utility of ultra-deep sequencing analysis of cfDNA from 126 non-small cell lung cancer (NSCLC) patients using the Ion AmpliSeq Cancer Hotspot Panel v2 (ICP) and validated these findings with droplet digital polymerase chain reaction (ddPCR)...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290262/gcc2-alk-as-a-targetable-fusion-in-lung-adenocarcinoma-and-its-enduring-clinical-responses-to-alk-inhibitors
#19
Junhong Jiang, Xue Wu, Xiaoling Tong, Wangzhi Wei, Anan Chen, Xiaonan Wang, Yang W Shao, Jianan Huang
OBJECTIVES: ALK, RET and ROS1 fusions have been identified as treatable targets in 5%-15% of non-small-cell lung cancers, and thanks to the advanced sequencing technologies, their new partner genes have been steadily detected. Here we identified a rare fusion of ALK (GCC2-ALK) in a patient with advanced lung adenocarcinoma and monitored the treatment efficacy of ALK inhibitors on this patient. We further performed in vitro functional studies of this fusion protein for evaluating its oncogenic potential...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29290257/primary-resistance-to-osimertinib-due-to-sclc-transformation-issue-of-t790m-determination-on-liquid-re-biopsy
#20
R Minari, P Bordi, M Del Re, F Facchinetti, F Mazzoni, F Barbieri, A Camerini, C E Comin, L Gnetti, C Azzoni, R Nizzoli, B Bortesi, E Rofi, P Petreni, N Campanini, G Rossi, R Danesi, M Tiseo
OBJECTIVES: EGFR T790M mutation is the most common mechanism of resistance to first-/second-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) and could be overcome by third-generation EGFR-TKIs, such as osimertinib. Liquid biopsy, a non-invasive technique used to test the presence of the resistant mutation, may help avoiding tissue re-biopsy. However, analysing only circulating-free DNA, information about other less frequent and coexisting resistance mechanisms may remain unrevealed...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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