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Cell-free tumor dna

Katherine D Westmoreland, Christopher C Stanley, Nathan D Montgomery, Bongani Kaimila, Edwards Kasonkanji, Nader Kim El-Mallawany, Peter Wasswa, Idah Mtete, Mercy Butia, Salama Itimu, Mary Chasela, Mary Mtunda, Maria Chikasema, Victor Makwakwa, Coxcilly Kampani, Bal M Dhungel, Marcia K Sanders, Robert Krysiak, Tamiwe Tomoka, N George Liomba, Dirk P Dittmer, Yuri Fedoriw, Satish Gopal
BACKGROUND: Contemporary descriptions of classical Hodgkin lymphoma (cHL) are lacking from sub-Saharan Africa where human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) are prevalent. METHODS: We describe a prospective cHL cohort in Malawi enrolled from 2013 to 2015. Patients received standardized treatment and evaluation, including HIV status and EBV testing of tumors and plasma. RESULTS: Among 31 patients with confirmed cHL, the median age was 19 years (range, 2-51 years) and 22 (71%) were male...
October 26, 2016: Pediatric Blood & Cancer
Wei-Ming Li, Chun-Nung Huang, Hung-Lung Ke, Ching-Chia Li, Yu-Ching Wei, Hsin-Chih Yeh, Lin-Li Chang, Chun-Hsiung Huang, Peir-In Liang, Bi-Wen Yeh, Ti-Chun Chan, Chien-Feng Li, Wen-Jeng Wu
Urothelial carcinoma (UC) occurs in the upper urinary tract (UTUC) and the urinary bladder (UBUC). The molecular pathogenesis of UC has not been fully elucidated. Through data mining of a published transcriptome of UBUC (GSE31684), we identified Minichromosome Maintenance Complex Component 2 (MCM2) and MCM10 as the two most significantly upregulated genes in UC progression among the MCM gene family, the key factors for the initiation of DNA replication. To validate the clinical significance of MCM2 and MCM10, immunohistochemistry, evaluated by H-score, was used in a pilot study of 50 UTUC and 50 UBUC samples...
October 21, 2016: Oncotarget
David T Miyamoto, Richard J Lee
The recent expansion of therapeutic options for the treatment of metastatic prostate cancer highlights the need for precision medicine approaches to enable the rational selection of appropriate therapies for individual patients. In this context, circulating biomarkers in the peripheral blood are attractive as readily accessible tools for predicting and monitoring therapeutic response. In the case of circulating tumor cells and circulating tumor DNA, they may also serve as a noninvasive means of assessing molecular aberrations in tumors at multiple time points before and during therapy...
October 19, 2016: Urologic Oncology
Lili Chen, Fangling Ji, Yongming Bao, Jing Xia, Lianying Guo, Jingyun Wang, Yachen Li
The greatest crux in the combination of chemotherapy and gene therapy is the construction of a feasible and biocompatible carrier for loading the therapeutic drug and gene simultaneously. Here, a new amphiphilic bifunctional pullulan derivative (named as PDP) synthesized by grafting lipophilic desoxycholic acid and low-molecular weight (1kDa) branched polyethylenimine onto the backbone of pullulan was evaluated as a nano-carrier for the co-delivery of drug and gene for potential cancer therapy. PDP exhibited good blood compatibility and low cytotoxicity in the hemolysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Peixin Dong, Ying Xiong, Hidemichi Watari, Sharon Jb Hanley, Yosuke Konno, Kei Ihira, Fumihiko Suzuki, Takahiro Yamada, Masataka Kudo, Junming Yue, Noriaki Sakuragi
Derepression of wild-type p53 by suppressing its negative inhibitor iASPP (Inhibitor of apoptosis-stimulating protein of p53) represents a potential therapeutic option for cervical cancer (CC). Here, we reported a novel functional significance of iASPP upregulation in cervical tumorigenesis: iASPP acts as a key promoter of CC cell proliferation, epithelial-mesenchymal transition, invasion and cancer stemness, by interacting with p53 to suppress p53-mediated transcription of target genes and reducing p53-responsive microRNA-34a levels...
October 21, 2016: Scientific Reports
Tushar Tomar, Steven de Jong, Nicolette G Alkema, Rieks L Hoekman, Gert Jan Meersma, Harry G Klip, Ate Gj van der Zee, G Bea A Wisman
BACKGROUND: In high-grade serous ovarian cancer (HGSOC), intrinsic and/or acquired resistance against platinum-containing chemotherapy is a major obstacle for successful treatment. A low frequency of somatic mutations but frequent epigenetic alterations, including DNA methylation in HGSOC tumors, presents the cancer epigenome as a relevant target for innovative therapy. Patient-derived xenografts (PDXs) supposedly are good preclinical models for identifying novel drug targets. However, the representativeness of global methylation status of HGSOC PDXs compared to their original tumors has not been evaluated so far...
October 20, 2016: Genome Medicine
Kaijun Di, Naomi Lomeli, Spencer D Wood, Christopher D Vanderwal, Daniela A Bota
Mitochondrial dysfunction is a hallmark of cancer biology. Tumor mitochondrial metabolism is characterized by an abnormal ability to function in scarce oxygen conditions through glycolysis (the Warburg effect), and accumulation of mitochondrial DNA defects are present in both hereditary neoplasia and sporadic cancers. Mitochondrial Lon is a major regulator of mitochondrial metabolism and the mitochondrial response to free radical damage, and plays an essential role in the maintenance and repair of mitochondrial DNA...
October 15, 2016: Oncotarget
Sarah Hrebien, Ben O'Leary, Matthew Beaney, Gaia Schiavon, Charlotte Fribbens, Amarjit Bhambra, Richard Johnson, Isaac Garcia-Murillas, Nicholas Turner
Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48-72 hours after collection...
2016: PloS One
Kuba Marciniak, Mirosław Kiedrowski, Danuta Gajewska, Andrzej Deptała, Dariusz Włodarek
The development of colorectal carcinoma is a multistep process of accumulation of mutations and epigenetic changes associated with DNA repair, proliferation, apoptosis, intra- and extracellular signaling, adhesion and other physiological functions of cells and tissues. A long period of development, high colorectal carcinoma-related mortality as well as significant social and economic costs due to this condition are prerequisites for seeking efficient methods of cancer prevention, including nutritional approach...
October 19, 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Qing-Shuo Zhang, Weiliang Tang, Matthew Deater, Ngoc Phan, Andrea N Marcogliese, Hui Li, Muhsen Al-Dhalimy, Angela Major, Susan Olson, Raymond J Monnat, Markus Grompe
Fanconi anemia is an inherited bone marrow failure disorder associated with a high incidence of leukemia and solid tumors. Bone marrow transplantation is currently the only curative therapy for the hematopoietic complications of this disorder. However, long-term morbidity and mortality remain very high and new therapeutics are badly needed. Here we show that the widely used diabetes drug metformin improves hematopoiesis and delays tumor formation in Fancd2(-/-) mice. Metformin is the first compound reported to improve both of these Fanconi anemia phenotypes...
October 18, 2016: Blood
Hideharu Kimura, Shingo Nishikawa, Hayato Koba, Taro Yoneda, Takashi Sone, Kazuo Kasahara
Epidermal growth factor receptor (EGFR) T790M mutation is associated with resistance to EGFR tyrosine kinase inhibitors' (EGFR-TKIs) in non-small cell lung cancer (NSCLC). The aims of this study are to develop a blood-based, non-invasive approach to detecting the EGFR T790M mutation in advanced NSCLC patients, using PointMan™ EGFR DNA Enrichment Kit which is a novel method for selective amplification of genotype specific sequences.Pairs of blood samples and tumor tissues were collected from NSCLC patients with an EGFR activating mutation and who were resistant to EGFR-TKI treatment...
2016: Advances in Experimental Medicine and Biology
Jelena Belic, Marina Koch, Peter Ulz, Martina Auer, Teresa Gerhalter, Sumitra Mohan, Katja Fischereder, Edgar Petru, Thomas Bauernhofer, Jochen B Geigl, Michael R Speicher, Ellen Heitzer
Recent progress in the analysis of cell-free DNA fragments (cell-free circulating tumor DNA, ctDNA) now allows monitoring of tumor genomes by non-invasive means. However, previous studies with plasma DNA from patients with cancer demonstrated highly variable allele frequencies of ctDNA. Comprehensive genome-wide analysis of tumor genomes is greatly facilitated when plasma DNA has increased amounts of ctDNA. In order to develop a fast and cost-effective pre-screening method for the identification of plasma samples suitable for further extensive qualitative analysis, we adapted the recently described FAST-SeqS method...
2016: Advances in Experimental Medicine and Biology
Svetlana N Tamkovich, Oleg S Tutanov, Danil S Serdukov, Maxim S Belenikin, Anatoliy G Shlikht, Natalia A Kirushina, Vladimir E Voytsitskiy, Yuri P Tsentalovich, Vsevolod A Tkachuk, Pavel P Laktionov
In the current study we have investigated the protein content of blood plasma deoxyribonucleoprotein complexes. The complexes were isolated using affinity chromatography with immobilized polyclonal anti-histone antibodies. Proteins were separated by SDS PAAGE and identified by MALDI-TOF mass-spectrometry. 111 and 56 proteins (excluding histones), respectively, were identified with a good score in deoxyribonucleoprotein complexes of healthy females and breast cancer patients. However, only four of these proteins were found in 30 % of all samples...
2016: Advances in Experimental Medicine and Biology
Erina Takai, Yasushi Totoki, Hiromi Nakamura, Mamoru Kato, Tatsuhiro Shibata, Shinichi Yachida
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. The genomic landscape of the PDAC genome features four frequently mutated genes (KRAS, CDKN2A, TP53, and SMAD4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Circulating cell-free DNA (cfDNA) is a promising resource to detect molecular characteristics of tumors, supporting the concept of "liquid biopsy".We determined the mutational status of KRAS in plasma cfDNA using multiplex droplet digital PCR in 259 patients with PDAC, retrospectively...
2016: Advances in Experimental Medicine and Biology
James J Hsieh, David Chen, Patricia I Wang, Mahtab Marker, Almedina Redzematovic, Ying-Bei Chen, S Duygu Selcuklu, Nils Weinhold, Nancy Bouvier, Kety H Huberman, Umesh Bhanot, Michael S Chevinsky, Parul Patel, Patrizia Pinciroli, Helen H Won, Daoqi You, Agnes Viale, William Lee, A Ari Hakimi, Michael F Berger, Nicholas D Socci, Emily H Cheng, Jennifer Knox, Martin H Voss, Maurizio Voi, Robert J Motzer
BACKGROUND: Metastatic renal cell carcinoma (RCC) patients are commonly treated with vascular endothelial growth factor (VEGF) inhibitors or mammalian target of rapamycin inhibitors. Correlations between somatic mutations and first-line targeted therapy outcomes have not been reported on a randomized trial. OBJECTIVE: To evaluate the relationship between tumor mutations and treatment outcomes in RECORD-3, a randomized trial comparing first-line everolimus (mTOR inhibitor) followed by sunitinib (VEGF inhibitor) at progression with the opposite sequence in 471 metastatic RCC patients...
October 14, 2016: European Urology
Yutong He, Xinyuan Zhang, Liqun Wang, Ziqiang Tian, Qingyi Liu, Jifang Yao, Yueping Liu, Chuanbao Li, Li Min, Baoen Shan
Non-small cell lung cancer (NSCLC) is a major public health problem worldwide and leads to a high mortality. NSCLC is always diagnosed in late stages because of its unapparent symptoms. However, cell-free DNA (cfDNA) may serve as a new potential biomarker to detect early stage of non‑small cell lung cancer. Here we recruited 10 non-small cell lung cancer patients to obtain fresh tumor tissue, peripheral blood lymphocytes (PBLs), and plasma. CfDNAs from 13 elderly people and 7 middle-age smokers were also extracted as controls...
October 12, 2016: International Journal of Oncology
Jing Xu, Yanjun Wang, Luzhu Yang, Yanfang Gao, Baoxin Li, Yan Jin
Human telomerase RNA (hTR), works as a template for synthesis of telomeric DNA repeats at the ends of linear eukaryotic chromosomes, is overexpressed in tumor cells and its concentration has a positive correlation with telomerase activity. The lack of facile and reliable method for detection of hTR in complex matric limited its application for clinical diagnosis. To address the limitation, herein, we proposed a facile and reliable flow cytometric assay for sensitive and specific detection of hTR by combing magnetic enrichment with signal amplification of DNA toehold strand displacement reaction (TSDR)...
August 13, 2016: Biosensors & Bioelectronics
Zuzana Sestakova, Katarina Kalavska, Lenka Hurbanova, Dana Jurkovicova, Jan Gursky, Michal Chovanec, Daniela Svetlovska, Vera Miskovska, Jana Obertova, Patrik Palacka, Katarina Rejlekova, Zuzana Sycova-Mila, Silvia Cingelova, Stanislav Spanik, Jozef Mardiak, Miroslav Chovanec, Michal Mego
Germ cell tumors (GCTs) are extraordinarily sensitive to cisplatin (CDDP)-based chemotherapy. DNA damage represents one of the most important factors contributing to toxic effects of CDDP-based chemotherapy. This study was aimed to evaluate the prognostic value of DNA damage level in peripheral blood lymphocytes (PBLs) from chemo-naïve GCT patients. PBLs isolated from 59 chemotherapy-naïve GCT patients were included into this prospective study. DNA damage levels in PBLs were evaluated by the Comet assay and scored as percentage tail DNA by the Metafer-MetaCyte analyzing software...
October 7, 2016: Oncotarget
Inessa Skrypkina, Liudmyla Tsyba, Kateryna Onyshchenko, Dmytro Morderer, Olena Kashparova, Oleksii Nikolaienko, Grigory Panasenko, Sergii Vozianov, Alina Romanenko, Alla Rynditch
The critical point for successful treatment of cancer is diagnosis at early stages of tumor development. Cancer cell-specific methylated DNA has been found in the blood of cancer patients, indicating that cell-free DNA (cfDNA) circulating in the blood is a convenient tumor-associated DNA marker. Therefore methylated cfDNA can be used as a minimally invasive diagnostic marker. We analysed the concentration of plasma cfDNA and methylation of six tumor suppressor genes in samples of 27 patients with renal cancer and 15 healthy donors as controls...
2016: Disease Markers
Pei-Chi Lee, Chien-Yu Lin, Cheng-Liang Peng, Ming-Jium Shieh
The development of a controlled-release drug delivery system has been an important objective for cancer therapy. To achieve the goal of sustained drug release for preventing the biotoxicity of platinum drugs, oxaliplatin was encapsulated into PEGylated multiwalled carbon nanotubes (MWNTs) decorated with superparamagnetic iron oxide (SPIO) for magnetic resonance imaging (MRI). The superparamagnetic properties and purification of SPIO/MWNT composites were achieved by annealing treatment during the fabrication process; the better hydrophilicity and biocompatibility were also accomplished subsequently after modification with polyethylene glycol (PEG)...
October 7, 2016: Biomaterials Science
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