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Cell-free tumor dna

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https://www.readbyqxmd.com/read/28526069/xlf-mediated-nhej-activity-in-hepatocellular-carcinoma-therapy-resistance
#1
Sitian Yang, Xiao Qi Wang
BACKGROUND: DNA repair pathways are used by cancer cells to overcome many standard anticancer treatments, causing therapy resistance. Here, we investigated the role of XRCC4-like factor (XLF), a core member of the non-homologous end joining (NHEJ) repair pathway, in chemoresistance in hepatocellular carcinoma (HCC). METHODS: qRT-PCR analysis and western blotting were performed to detect expression levels of genes and proteins related to NHEJ. NHEJ repair capacity was assessed in vitro (cell-free) and in vivo by monitoring the activity of the NHEJ pathway...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28525901/direct-inhibition-of-stat-signaling-by-platinum-drugs-contributes-to-their-anti-cancer-activity
#2
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...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523411/apurinic-apyrimidinic-endonuclease-1-ape1-is-overexpressed-in-malignant-transformation-of-salivary-gland-pleomorphic-adenoma
#3
Leorik Pereira Silva, Thalita Santana, Bruno Tavares Sedassari, Suzana Machado de Sousa, Ana Paula Veras Sobral, Roseana de Almeida Freitas, Carlos Augusto Galvão Barboza, Lélia Batista de Souza
DNA repair systems play a critical role in protecting the human genome against cumulative damage. The apurinic/apyrimidinic endonuclease 1 is a protein involved in DNA base excision repair and its expression still needs to be investigated in salivary gland tumors. The objective of this study is to analyze the immunoexpression of apurinic/apyrimidinic endonuclease 1 in pleomorphic adenomas and carcinomas ex pleomorphic adenomas of the salivary glands. A total of 33 pleomorphic adenomas and 16 carcinomas ex pleomorphic adenomas of the salivary glands underwent immunohistochemical study by the polymeric biotin-free technique...
May 18, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28522829/somatic-tumor-mutations-detected-by-targeted-next-generation-sequencing-in-minute-amounts-of-serum-derived-cell-free-dna
#4
Marjolein J A Weerts, Ronald van Marion, Jean C A Helmijr, Corine M Beaufort, Niels M G Krol, Anita M A C Trapman-Jansen, Winand N M Dinjens, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens
The use of blood-circulating cell-free DNA (cfDNA) as 'liquid-biopsy' is explored worldwide, with hopes for its potential in providing prognostic or predictive information in cancer treatment. In exploring cfDNA, valuable repositories are biobanks containing material collected over time, however these retrospective cohorts have restrictive resources. In this study, we aimed to detect tumor-specific mutations in only minute amounts of serum-derived cfDNA by using a targeted next generation sequencing (NGS) approach...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28516087/dna-sequence-analysis-in-clinical-medicine-proceeding-cautiously
#5
REVIEW
Moyra Smith
Delineation of underlying genomic and genetic factors in a specific disease may be valuable in establishing a definitive diagnosis and may guide patient management and counseling. In addition, genetic information may be useful in identification of at risk family members. Gene mapping and initial genome sequencing data enabled the development of microarrays to analyze genomic variants. The goal of this review is to consider different generations of sequencing techniques and their application to exome sequencing and whole genome sequencing and their clinical applications...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28515105/free-circulating-methylated-dna-in-blood-for-diagnosis-staging-prognosis-and-monitoring-of-head-and-neck-squamous-cell-carcinoma-patients-an-observational-prospective-cohort-study
#6
Andreas Schröck, Annette Leisse, Luka de Vos, Heidrun Gevensleben, Freya Dröge, Alina Franzen, Malin Wachendörfer, Friederike Schröck, Joerg Ellinger, Marcus Teschke, Timo Wilhelm-Buchstab, Jennifer Landsberg, Stefan Holdenrieder, Gunther Hartmann, John K Field, Friedrich Bootz, Glen Kristiansen, Dimo Dietrich
BACKGROUND: Circulating cell-free DNA methylation testing in blood has recently received regulatory approval for screening of colorectal cancer. Its application in other clinical settings, including staging, prognosis, prediction, and recurrence monitoring is highly promising, and of particular interest in head and neck squamous cell carcinomas (HNSCC) that represent a heterogeneous group of cancers with unsatisfactory treatment guidelines. METHODS: Short stature homeobox 2 (SHOX2) and septin 9 (SEPT9) DNA methylation in plasma from 649 prospectively enrolled patients (training study: 284 HNSCC/122 control patients; testing study: 141 HNSCC/102 control patients) was quantified before treatment and longitudinally during surveillance...
May 17, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28511612/ngs-analysis-on-tumor-tissue-and-cfdna-for-genotype-directed-therapy-in-metastatic-nsclc-patients-between-hope-and-hype
#7
Alexander T Falk, Simon Heeke, Véronique Hofman, Virginie Lespinet, Camille Ribeyre, Olivier Bordone, Michel Poudenx, Josiane Otto, Georges Garnier, Olivier Castelnau, Joël Guigay, Sylvie Leroy, Charles-Hugo Marquette, Paul Hofman, Marius Ilié
The advent of genomic based precision medicine led to the implementation of biomarker testing in metastatic non-small cell lung cancer (NSCLC) patients. Next generation sequencing (NGS) has been recently implemented to routine diagnostic requirements in lung oncology. Areas covered: Two cases of patients with metastatic NSCLC for whom NGS analysis performed on both tumor and liquid biopsy has not improved the clinical course of their disease are reported. These cases illustrate the difficulty of the so-called "personalized or precision" medicine in clinical routine practice for metastatic NSCLC...
May 17, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28506684/study-of-preanalytic-and-analytic-variables-for-clinical-next-generation-sequencing-of-circulating-cell-free-nucleic-acid
#8
Meenakshi Mehrotra, Rajesh R Singh, Wei Chen, Richard S P Huang, Alaa A Almohammedsalim, Bedia A Barkoh, Crystal M Simien, Marcos Hernandez, Carmen Behrens, Keyur P Patel, Mark J Routbort, Russell R Broaddus, L Jeffrey Medeiros, Ignacio I Wistuba, Scott Kopetz, Rajyalakshmi Luthra
Detection of mutations in plasma circulating cell-free DNA (cfDNA) by next-generation sequencing (NGS) has opened up new possibilities for monitoring treatment response and disease progression in patients with solid tumors. However, implementation of cfDNA genotyping in diagnostic laboratories requires systematic assessment of preanalytical parameters and analytical performance of NGS platforms. We assessed the effects of peripheral blood collection tube and plasma separation time on cfDNA yield and integrity and performance of the Ion PGM, Proton, and MiSeq NGS platforms...
May 12, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28504856/cell-free-dna-copy-number-variations-in-plasma-from-colorectal-cancer-patients
#9
Jian Li, Rachel L Dittmar, Shu Xia, Huijuan Zhang, Meijun Du, Chiang-Ching Huang, Brooke R Druliner, Lisa Boardman, Liang Wang
To evaluate clinical utility of cell free DNA (cfDNA), we performed whole genome sequencing to systematically examine plasma cfDNA copy number variations (CNVs) in a cohort of patients with colorectal cancer (CRC, n=80), polyps (n=20) and healthy controls (n=35). We initiallycompared cfDNA yield in 20 paired serum-plasma samples and observed significantly higher cfDNA concentration in serum (median=81.20ng, range 7.18-500ng/ml) than in plasma (median=5.09ng, range 3.76-62.8ng/ml) (p<0.0001). However, tumor-derived cfDNA content was significantly lower in serum than in matched plasma samples tested...
May 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28500398/comparative-clinical-utility-of-tumor-genomic-testing-and-cell-free-dna-in-metastatic-breast-cancer
#10
Kara N Maxwell, Danielle Soucier-Ernst, Emin Tahirovic, Andrea B Troxel, Candace Clark, Michael Feldman, Christopher Colameco, Bijal Kakrecha, Melissa Langer, David Lieberman, Jennifer J D Morrissette, Matt R Paul, Tien-Chi Pan, Stephanie Yee, Natalie Shih, Erica Carpenter, Lewis A Chodosh, Angela DeMichele
PURPOSE: Breast cancer metastases differ biologically from primary disease; therefore, metastatic biopsies may assist in treatment decision making. Commercial genomic testing of both tumor and circulating tumor DNA have become available clinically, but utility of these tests in breast cancer management remains unclear. METHODS: Patients undergoing a clinically indicated metastatic tumor biopsy were consented to the ongoing METAMORPH registry. Tumor and blood were collected at the time of disease progression before subsequent therapy, and patients were followed for response on subsequent treatment...
May 12, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28499389/a-phase-ii-trial-of-autologous-dendritic-cell-vaccination-and-radiochemotherapy-following-fluorescence-guided-surgery-in-newly-diagnosed-glioblastoma-patients
#11
Susana Inogés, Sonia Tejada, Ascensión López-Díaz de Cerio, Jaime Gállego Pérez-Larraya, Jaime Espinós, Miguel Angel Idoate, Pablo Daniel Domínguez, Reyes García de Eulate, Javier Aristu, Maurizio Bendandi, Fernando Pastor, Marta Alonso, Enrique Andreu, Felipe Prósper Cardoso, Ricardo Díez Valle
BACKGROUND: Prognosis of patients with glioblastoma multiforme (GBM) remains dismal, with median overall survival (OS) of about 15 months. It is therefore crucial to search alternative strategies that improve these results obtained with conventional treatments. In this context, immunotherapy seems to be a promising therapeutic option. We hypothesized that the addition of tumor lysate-pulsed autologous dendritic cells (DCs) vaccination to maximal safe resection followed by radiotherapy and concomitant and adjuvant temozolomide could improve patients' survival...
May 12, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28498430/uva-induced-upregulation-of-progerin-suppresses-53bp1%C3%A2-mediated-nhej-dsb-repair-in-human-keratinocytes-via-progerin-lamin%C3%A2-a-complex-formation
#12
Xin Huang, Yun Pan, Di Cao, Sheng Fang, Kun Huang, Jin Chen, Aijun Chen
Ultraviolet (UV) radiation is the primary risk factor underlying photoaging and photocarcinogenesis. Mounting research has focused on the role of DNA damage response pathways in UV-induced double-strand break (DSB) repair. In the present study, we hypothesized that UVA-induced aberrant progerin upregulation may adversely affect p53-binding protein 1 (53BP1)-mediated non-homologous end joining (NHE) DSB repair in human keratinocytes. Basal cell carcinoma (BCC) tumors and matching normal skin tissue were sampled (n=200) to investigate whether human keratinocytes display dysregulated progerin expression as a function of advancing age and BCC status...
April 26, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28492516/circulating-cell-free-dna-and-circulating-tumor-cells-as-prognostic-and-predictive-biomarkers-in-advanced-non-small-cell-lung-cancer-patients-treated-with-first-line-chemotherapy
#13
Simona Coco, Angela Alama, Irene Vanni, Vincenzo Fontana, Carlo Genova, Maria Giovanna Dal Bello, Anna Truini, Erika Rijavec, Federica Biello, Claudio Sini, Giovanni Burrafato, Claudia Maggioni, Giulia Barletta, Francesco Grossi
Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA quantification was performed by quantitative PCR (qPCR) whereas CTCs were isolated by the ScreenCell Cyto (ScreenCell, Paris, France) device and enumerated according to malignant features...
May 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28489509/akt-inhibition-in-solid-tumors-with-akt1-mutations
#14
David M Hyman, Lillian M Smyth, Mark T A Donoghue, Shannon N Westin, Philippe L Bedard, Emma J Dean, Hideaki Bando, Anthony B El-Khoueiry, José A Pérez-Fidalgo, Alain Mita, Jan H M Schellens, Matthew T Chang, Jonathan B Reichel, Nancy Bouvier, S Duygu Selcuklu, Tara E Soumerai, Jean Torrisi, Joseph P Erinjeri, Helen Ambrose, J Carl Barrett, Brian Dougherty, Andrew Foxley, Justin P O Lindemann, Robert McEwen, Martin Pass, Gaia Schiavon, Michael F Berger, Sarat Chandarlapaty, David B Solit, Udai Banerji, José Baselga, Barry S Taylor
Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST)...
May 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28489348/novel-curcumin-liposome-modified-with-hyaluronan-targeting-cd44-plays-an-anti-leukemic-role-in-acute-myeloid-leukemia-in-vitro-and-in-vivo
#15
Dan Sun, Jian-Kang Zhou, Linshu Zhao, Zhe-Yu Zheng, Jiao Li, Wenchen Pu, Shaoyang Liu, Xue-Sha Liu, Shu-Jun Liu, Yu Zheng, Yun Zhao, Yong Peng
Curcumin has been widely used as a food additive for centuries and has been recently explored for its anti-inflammatory and antitumor properties. Although curcumin is pharmacologically safe and efficacious to certain cancers, its role against acute myeloid leukemia (AML) still remains unclear, and it lacks clinical application due to low water solubility and low in vivo bioavailability. To address these issues, we developed a novel curcumin liposome modified with hyaluronan (HA-Cur-LPs) to specifically deliver curcumin to AML by targeting CD44 on AML cell surface...
May 10, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28485169/plasma-cell-free-dna-integrity-plus-circulating-tumor-cells-a-potential-biomarker-of-no-distant-metastasis-breast-cancer
#16
W Wang, M Liang, G Ma, L Li, W Zhou, T Xia, H Xie, S Wang
Cell-free DNA integrity (cfDI) is a promising diagnostic and prognostic biomarker in breast cancer. However, no specific study has evaluated the diagnostic ability of cfDI in patients with no distant metastasis breast cancer (no-MBC) and benign breast tumor (BBT) to date. We assessed the plasma cfDI of 84 patients with no-MBC and 30 patients with BBT using quantitative PCR and compared it with circulating tumor cells (CTCs) and carbohydrate antigen 153 (CA153). The no-MBC group had significantly lower mean cfDI (0...
May 9, 2017: Neoplasma
https://www.readbyqxmd.com/read/28484715/plasma-circulating-tumor-dna-levels-for-the-monitoring-of-melanoma-patients-landscape-of-available-technologies-and-clinical-applications
#17
REVIEW
Benoit Busser, Julien Lupo, Lucie Sancey, Stéphane Mouret, Patrice Faure, Joel Plumas, Laurence Chaperot, Marie Thérèse Leccia, Jean Luc Coll, Amandine Hurbin, Pierre Hainaut, Julie Charles
Melanoma is a cutaneous cancer with an increasing worldwide prevalence and high mortality due to unresectable or metastatic stages. Mutations in BRAF, NRAS, or KIT are present in more than 60% of melanoma cases, but a useful blood-based biomarker for the clinical monitoring of melanoma patients is still lacking. Thus, the analysis of circulating tumor cells (CTCs) and/or cell-free circulating tumor DNA (ctDNA) analysis from blood (liquid biopsies) appears to be a promising noninvasive, repeatable, and systemic sampling tool for detecting and monitoring melanoma...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28484252/wnt-inhibitory-factor-1-wif1-methylation-and-its-association-with-clinical-prognosis-in-patients-with-chondrosarcoma
#18
Pei Liu, Jacson K Shen, Francis J Hornicek, Fuyun Liu, Zhenfeng Duan
Chondrosarcoma (CS) is a rare cancer, but it is the second most common primary malignant bone tumor and highly resistant to conventional chemotherapy and radiotherapy. Aberrant DNA methylation in the promoter CpG island of Wnt inhibitory factor 1 (WIF1) has been observed in different cancers. However, no studies have shown the relationship between WIF1 methylation and CS. In this study, we found promoter methylated WIF1 in both CS cell lines (CS-1 and SW1353) and tumor tissues. Western blot analysis confirmed loss WIF1 expression and activation of Wnt pathway proteins (Wnt5a/b, LRP6, and Dvl2)...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28482344/norad-expression-is-associated-with-adverse-prognosis-in-esophageal-squamous-cell-carcinoma
#19
Xiaoliang Wu, Zuan-Fu Lim, Zhongwen Li, Ling Gu, Wenjuan Ma, Qianghua Zhou, Huifang Su, Xing Wang, Xianzi Yang, Zhenfeng Zhang
BACKGROUND: NORAD (non-coding RNA-activated by DNA damage) is a conserved, abundant, and broadly expressed long non-coding RNA, which functions to preserve genome stability. However, its prognostic significance in esophageal squamous cell carcinoma (ESCC) remains unclear. MATERIAL AND METHODS: The expression of NORAD was detected by quantitative real-time polymerase chain reaction in pairs of tumorous and adjacent normal tissues derived from 106 ESCC patients. We analyzed the potential relationship between NORAD expression levels in tumor tissues and clinicopathological features of ESCC patients and clinical outcome...
May 10, 2017: Oncology Research and Treatment
https://www.readbyqxmd.com/read/28480996/the-pd-1-pd-l1-axis-and-human-papilloma-virus-in-patients-with-head-and-neck-cancer-after-adjuvant-chemoradiotherapy-a-multicentre-study-of-the-german-cancer-consortium-radiation-oncology-group-dktk-rog
#20
Panagiotis Balermpas, Franz Rödel, Mechthild Krause, Annett Linge, Fabian Lohaus, Michael Baumann, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Eleni Gkika, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Stefan Stangl, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Gabriele Multhoff, Stephanie E Combs, Stefan Welz, Daniel Zips, Su Yin Lim, Claus Rödel, Emmanouil Fokas
We examined the prognostic role of PD-1+ and CD8+ tumor infiltrating lymphocytes (TILs), and PD-L1+ cells in patients with squamous cell carcinoma of the head and neck (SCCHN) treated with surgery and postoperative chemoradiotherapy (CRT). FFPE samples from 161 patients were immunohistochemically stained for PD-1, CD8 and PD-L1. The immune marker expression was correlated with clinicopathologic characteristics, and overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of HPV16 DNA/p16 status...
May 8, 2017: International Journal of Cancer. Journal International du Cancer
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