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https://www.readbyqxmd.com/read/28937589/viral-cellular-dna-junctions-as-molecular-markers-for-assessing-intra-tumor-heterogeneity-in-cervical-cancer-and-for-the-detection-of-circulating-tumor-dna
#1
Katrin Carow, Mandy Gölitz, Maria Wolf, Norman Häfner, Lars Jansen, Heike Hoyer, Elisabeth Schwarz, Ingo B Runnebaum, Matthias Dürst
The development of cervical cancer is frequently accompanied by the integration of human papillomaviruses (HPV) DNA into the host genome. Viral-cellular junction sequences, which arise in consequence, are highly tumor specific. By using these fragments as markers for tumor cell origin, we examined cervical cancer clonality in the context of intra-tumor heterogeneity. Moreover, we assessed the potential of these fragments as molecular tumor markers and analyzed their suitability for the detection of circulating tumor DNA in sera of cervical cancer patients...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28932630/the-safety-efficacy-and-treatment-outcomes-of-a-combination-of-low-dose-decitabine-treatment-in-patients-with-recurrent-ovarian-cancer
#2
Yan Zhang, Qian Mei, Yang Liu, Xiang Li, Malcolm V Brock, Meixia Chen, Liang Dong, Lu Shi, Yao Wang, Mingzhou Guo, Jing Nie, Weidong Han
Purpose: DNA demethylating agents have shown clinical effectiveness in hematological and solid tumors. This trial tested the safety, efficacy, and treatment outcomes of decitabine-based chemotherapy or combined with immunotherapy in recurrent ovarian cancer patients. Patients and methods: Fifty-five patients with recurrent ovarian cancer were enrolled and 52 were assessable for clinical response and survival. Patients either received 5-d decitabine treatment, followed by reduced-dose of paclitaxel/carboplatin administration (DTC cohort), or the aforementioned regimen combined with cytokine-induced killer cells therapy (DTC+CIK cohort)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931069/methylation-associated-transcriptional-repression-of-elovl5-in-novel-colorectal-cancer-cell-lines
#3
Arnoud Boot, Jan Oosting, Jaap D H van Eendenburg, Peter J K Kuppen, Hans Morreau, Tom van Wezel
Genetic and epigenetic alterations mark colorectal cancer (CRC). Global hypomethylation is observed in nearly all CRC, but a distinct subset of CRC show the CpG Island Methylator Phenotype (CIMP). These tumors show DNA hypermethylation of a specific subset of CpG islands, resulting in transcriptional downregulation of nearby genes. Recently we reported the establishment of novel CRC cell lines derived from primary and metastatic CRC tissues. In this study we describe the DNA methylation profiling of these low passage CRC cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28928874/ercc1_202-is-a-prognostic-biomarker-in-advanced-stage-non-small-cell-lung-cancer-patients-treated-with-platinum-based-chemotherapy
#4
Xiyong Wang, Xiaoli Zhu, Hongming Zhang, Xiaobo Fan, Xiulei Xue, Yan Chen, Chenbo Ding, Jianwen Zhao, Guoqiu Wu
Purpose: To develop a qPCR method to examine the 202 isoform of excision repair cross-complementation group 1 (ERCC1_202) and to evaluate its clinical utility as a predictive biomarker for platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Methods: The relative complementary DNA (cDNA) quantification for ERCC1_202 was conducted using a fluorescence-based, real-time detection method and β-actin was used as a reference gene. Results: A strong correlation was observed between ERCC1_202 mRNA and ERCC1 mRNA levels in NSCLC cells (P < 0...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28926265/tobacco-mosaic-virus-delivered-cisplatin-restores-efficacy-in-platinum-resistant-ovarian-cancer-cells
#5
Christina E Franke, Anna E Czapar, Ravi B Patel, Nicole F Steinmetz
Platinum resistance in ovarian cancer is the major determinant of disease prognosis. Resistance can first appear at the onset of disease or develop in response to platinum-based chemotherapy. Due to poor response to alternate chemotherapies and lack of targeted therapies, there is an urgent clinical need for a new avenue toward treatment of platinum-resistant (PR) ovarian cancer. Nanoscale delivery systems hold potential to overcome resistance mechanisms. In this work, we present tobacco mosaic virus (TMV) as a nanocarrier for cisplatin for treatment of PR ovarian cancer cells...
September 19, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28925386/5-hydroxymethylcytosine-signatures-in-circulating-cell-free-dna-as-diagnostic-biomarkers-for-human-cancers
#6
Wenshuai Li, Xu Zhang, Xingyu Lu, Lei You, Yanqun Song, Zhongguang Luo, Jun Zhang, Ji Nie, Wanwei Zheng, Diannan Xu, Yaping Wang, Yuanqiang Dong, Shulin Yu, Jun Hong, Jianping Shi, Hankun Hao, Fen Luo, Luchun Hua, Peng Wang, Xiaoping Qian, Fang Yuan, Lianhuan Wei, Ming Cui, Taiping Zhang, Quan Liao, Menghua Dai, Ziwen Liu, Ge Chen, Katherine Meckel, Sarbani Adhikari, Guifang Jia, Marc B Bissonnette, Xinxiang Zhang, Yupei Zhao, Wei Zhang, Chuan He, Jie Liu
DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals...
September 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28924235/single-nucleotide-polymorphisms-of-nucleotide-excision-repair-pathway-are-significantly-associated-with-outcomes-of-platinum-based-chemotherapy-in-lung-cancer
#7
Xiao Song, Shiming Wang, Xuan Hong, Xiaoying Li, Xueying Zhao, Cong Huai, Hongyan Chen, Zhiqiang Gao, Ji Qian, Jiucun Wang, Baohui Han, Chunxue Bai, Qiang Li, Junjie Wu, Daru Lu
Nucleotide excision repair (NER) pathway plays critical roles in repairing DNA disorders caused by platinum. To comprehensively understand the association between variants of NER and clinical outcomes of platinum-based chemotherapy, 173 SNPs in 27 genes were selected to evaluate association with toxicities and efficiency in 1004 patients with advanced non-small cell lung cancer. The results showed that consecutive significant signals were observed in XPA, RPA1, POLD1, POLD3. Further subgroup analysis showed that GTF2H4 presented consecutive significant signals in clinical benefit among adenocarcimoma...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28921800/initial-testing-stage-1-of-m6620-formerly-vx-970-a-novel-atr-inhibitor-alone-and-combined-with-cisplatin-and-melphalan-by-the-pediatric-preclinical-testing-program
#8
Raushan T Kurmasheva, Dias Kurmashev, C Patrick Reynolds, Min Kang, Jianwrong Wu, Peter J Houghton, Malcolm A Smith
BACKGROUND: M6620 is a novel inhibitor of the DNA damage repair enzyme ATR, and has potentiated the activity of cisplatin and irinotecan in non-small cell lung cancer and colon cancer xenografts, respectively. PROCEDURES: M6620 was tested in vitro at concentrations ranging from 1.0 nM to 10.0 μM and at 75 nM in combination with cisplatin or melphalan. M6620 was tested against 24 solid tumor xenografts alone and in combination with cisplatin. Cisplatin was administered intraperitoneally on days 1 and 8 at a dose of 5 mg/kg...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28915616/tdp-43-hdac6-axis-promoted-tumor-progression-and-regulated-nutrient-deprivation-induced-autophagy-in-glioblastoma
#9
Tzu-Wei Lin, Ming-Teh Chen, Liang-Ting Lin, Pin-I Huang, Wen-Liang Lo, Yi-Ping Yang, Kai-Hsi Lu, Yi-Wei Chen, Shih-Hwa Chiou, Cheng-Wen Wu
Glioblastoma Multiforme (GBM) is a lethal primary brain tumor with poor survival lifespan and dismal outcome. Surgical resection of GBM is greatly limited due to the biological significance of brain, giving rise to tumor relapse in GBM patients. Transactive response DNA binding protein-43 (TDP-43) is a DNA/RNA-binding protein known for causing neurodegenerative diseases through post-translational modification; but little is known about its involvement in cancer development. In this study, we found that nutrient deprivation in GBM cell lines elevated TDP-43 expression by a mechanism of evasion from ubiquitin-dependent proteolytic pathway, and subsequently activated the autophagy process...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915599/copy-number-variations-of-circulating-cell-free-dna-in-urothelial-carcinoma-of-the-bladder-patients-treated-with-radical-cystectomy-a-prospective-study
#10
Armin Soave, Felix K-H Chun, Timo Hillebrand, Michael Rink, Lars Weisbach, Bettina Steinbach, Margit Fisch, Klaus Pantel, Heidi Schwarzenbach
The aim of the present study was to establish a rapid profiling method using multiplex ligation-dependent probe amplification (MLPA) and characterize copy number variations (CNV) in circulating, cell-free DNA (cfDNA) in 85 urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). MLPA was tested for the use of cfDNA extracted from serum and plasma by various commercial extraction kits. Eighteen probes served as reference to control denaturation, ligation and amplification efficiency...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915002/microrna-catalyzed-cancer-therapeutics-based-on-dna-programmed-nanoparticle-complex
#11
Xucheng Luo, Zhi Li, Ganglin Wang, Xuewen He, Xiaoqin Shen, Quanhong Sun, Li Wang, Renye Yue, Nan Ma
The use of cancer-relevant microRNA molecules as endogenous drug release stimuli is promising for personalized cancer treatment yet remains a great challenge because of their low abundance. Herein, we report a new type of microRNA-catalyzed drug release system based on DNA-programmed gold nanoparticle (GNP)-quantum dot (QD) complex. We show that a trace amount of miRNA-21 molecules could specifically catalyze the disassembly of doxorubicin (Dox)-loaded GNP-QDs complex through entropy driven process, during which the Dox-intercalating sites are destructed for drug release...
September 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28912426/deconvolution-of-dna-methylation-identifies-differentially-methylated-gene-regions-on-1p36-across-breast-cancer-subtypes
#12
Alexander J Titus, Gregory P Way, Kevin C Johnson, Brock C Christensen
Breast cancer is a complex disease consisting of four distinct molecular subtypes. DNA methylation-based (DNAm) studies in tumors are complicated further by disease heterogeneity. In the present study, we compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution to control for cellular heterogeneity. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P)...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911086/large-scale-prospective-screening-of-egfr-mutations-in-the-blood-of-advanced-nsclc-patients-to-guide-treatment-decisions
#13
C Mayo-de-Las-Casas, N Jordana-Ariza, M Garzón-Ibañez, A Balada-Bel, J Bertrán-Alamillo, S Viteri-Ramírez, N Reguart, M A Muñoz-Quintana, P Lianes-Barragan, C Camps, E Jantús, J Remon-Massip, S Calabuig, D Aguiar, M L Gil, N Viñolas, A K Santos-Rodríguez, M Majem, B García-Peláez, S Villatoro, A Pérez-Rosado, J C Monasterio, E Ovalle, M J Catalán, R Campos, D Morales-Espinosa, A Martínez-Bueno, M González-Cao, X González, I Moya-Horno, A E Sosa, N Karachaliou, R Rosell, M A Molina-Vila
Background: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Patients and methods: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28911069/clinical-utility-of-circulating-dna-analysis-for-rapid-detection-of-actionable-mutations-to-select-metastatic-colorectal-patients-for-anti-egfr-treatment
#14
A R Thierry, S El Messaoudi, C Mollevi, J L Raoul, R Guimbaud, D Pezet, P Artru, E Assenat, C Borg, M Mathonnet, C De La Fouchardière, O Bouché, C Gavoille, C Fiess, B Auzemery, R Meddeb, E Lopez-Crapez, C Sanchez, B Pastor, M Ychou
Background: While tumor-tissue remains the 'gold standard' for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care. Patients and methods: Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients)...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28905672/the-influence-of-ketogenic-therapy-on-the-5-r-s-of-radiobiology
#15
Rainer J Klement
PURPOSE: Radiotherapy (RT) is a mainstay in the treatment of solid tumors and works by inducing free radical stress in tumor cells, leading to loss of reproductive integrity. The optimal treatment strategy has to consider damage to both tumor and normal cells and is determined by five factors known as the 5 R's of radiobiology: Reoxygenation, DNA Repair, Radiosensitivity, Redistribution in the cell cycle and Repopulation. The aim of this review is (i) to present evidence that these 5 R's are strongly influenced by cellular and whole body metabolism that in turn can be modified through ketogenic therapy in form of ketogenic diets and short term fasting, and (ii) to stimulate new research into this field including some research questions deserving further study...
September 14, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28905136/highly-sensitive-detection-of-esr1-mutations-in-cell-free-dna-from-patients-with-metastatic-breast-cancer-using-molecular-barcode-sequencing
#16
Nanae Masunaga, Naofumi Kagara, Daisuke Motooka, Shota Nakamura, Tomohiro Miyake, Tomonori Tanei, Yasuto Naoi, Masafumi Shimoda, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
PURPOSE: We aimed to develop a highly sensitive method to detect ESR1 mutations in cell-free DNA (cfDNA) using next-generation sequencing with molecular barcode (MB-NGS) targeting the hotspot segment (c.1600-1713). METHODS: The sensitivity of MB-NGS was tested using serially diluted ESR1 mutant DNA and then cfDNA samples from 34 patients with metastatic breast cancer were analyzed with MB-NGS. The results of MB-NGS were validated in comparison with conventional NGS and droplet digital PCR (ddPCR)...
September 13, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28904918/evaluation-of-genetic-polymorphisms-in-glutathione-s-transferase-theta1-glutathione-s-transferase-mu1-and-glutathione-s-transferase-mu3-in-oral-leukoplakia-and-oral-squamous-cell-carcinoma-with-deleterious-habits-using-polymerase-chain-reaction
#17
Ayyagari Kameswara Rao, Peela Parameswar, Sumit Majumdar, Divya Uppala, Sreekanth Kotina, Naga Himabindu Vennamaneni
CONTEXT: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the world. As per previous studies, most patients who develop oral cancer are elderly males who are heavy users of tobacco and alcohol; however, the incidence is increasing in younger individuals and in those who neither smoke nor drink. Many of the genes that code for the detoxification enzymes are polymorphic with abnormal activity profiles. AIMS AND OBJECTIVES: The aim of this study was to evaluate the risk of development of oral leukoplakia (OLP) and OSCC in glutathione S-transferase polymorphisms genes in the east coast of Andhra Pradesh population with tobacco consumption habit and habit-free controls using polymerase chain reaction (PCR-restriction fragment length polymorphism)...
July 2017: International Journal of Applied and Basic Medical Research
https://www.readbyqxmd.com/read/28903362/cell-free-circulating-dna-integrity-is-an-independent-predictor-of-impending-breast-cancer-recurrence
#18
Jie Cheng, Katarina Cuk, Jörg Heil, Michael Golatta, Sarah Schott, Christof Sohn, Andreas Schneeweiss, Barbara Burwinkel, Harald Surowy
Non-invasive blood-based molecule markers are evaluated as promising biomarkers these days. Here we investigated the potential of cell-free circulating DNA Integrity (cfDI) as blood-based marker for the prediction of recurrence during the follow-up of breast cancer patients within a prospective study cohort. cfDI was determined in plasma of 212 individuals, by measuring ALU and LINE1 repetitive DNA elements using quantitative PCR. A significant decrease of cfDI in recurrent breast cancer patients was observed...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903353/direct-inhibition-of-stat-signaling-by-platinum-drugs-contributes-to-their-anti-cancer-activity
#19
Stanleyson V Hato, Carl G Figdor, Susumu Takahashi, Anja E Pen, Altuna Halilovic, Kalijn F Bol, Angela Vasaturo, Yukie Inoue, Nienke de Haas, Dagmar Verweij, Carla M L Van Herpen, Johannes H Kaanders, Johan H J M van Krieken, Hanneke W M Van Laarhoven, Gerrit K J Hooijer, Cornelis J A Punt, Akira Asai, I Jolanda M de Vries, W Joost Lesterhuis
Platinum-based chemotherapeutics are amongst the most powerful anti-cancer drugs. Although their exact mechanism of action is not well understood, it is thought to be mediated through covalent DNA binding. We investigated the effect of platinum-based chemotherapeutics on signaling through signal transducer and activator of transcription (STAT) proteins, which are involved in many oncogenic signaling pathways. We performed in vitro experiments in various cancer cell lines, investigating the effects of platinum chemotherapeutics on STAT phosphorylation and nuclear translocation, the expression of STAT-modulating proteins and downstream signaling pathways...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903321/alu-based-cell-free-dna-a-novel-biomarker-for-screening-of-gastric-cancer
#20
Chen Qian, Shaoqing Ju, Jing Qi, Jianmei Zhao, Xianjuan Shen, Rongrong Jing, Juan Yu, Li Li, Yingjuan Shi, Lurong Zhang, Zhiwei Wang, Hui Cong
Gastric cancer (GC) is the fourth most common cancer and the second major cause of cancer-related deaths worldwide. In our previous study, a novel and sensitive method for quantifying cell-free DNA (CFD) in human blood was established and tested for its ability to predict patients with tumor. We want to investigate CFD expression in the sera of GC patients in an attempt to explore the clinical significance of CFD in improving the early screening of GC and monitoring GC progression by the branched DNA (bDNA)-based Alu assay...
August 15, 2017: Oncotarget
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