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https://www.readbyqxmd.com/read/28306358/the-genetics-of-gastroesophageal-adenocarcinoma-and-the-use-of-circulating-cell-free-dna-for-disease-detection-and-monitoring
#1
Mark R Openshaw, Catherine J Richards, David S Guttery, Jacqueline A Shaw, Anne L Thomas
Gastroesophageal adenocarcinoma (GOA) is a frequently occurring cancer worldwide with a poor clinical outcome. Adenocarcinomas of the oesophagus and gastroesophageal junction have shown a recent increase in frequency, therefore there is need to increase our understanding of GOA in order to improve our ability to detect, monitor and treat the disease. Areas covered: The authors discuss the current classification of GOA in the context of recent changes in incidence. The authors also discuss developments in the understanding of disease biology and recent discoveries from whole genome and whole exome sequencing, and studies in immunotherapy...
March 17, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28303898/circulating-tumour-dna-reflects-treatment-response-and-clonal-evolution-in-chronic-lymphocytic-leukaemia
#2
Paul Yeh, Tane Hunter, Devbarna Sinha, Sarah Ftouni, Elise Wallach, Damian Jiang, Yih-Chih Chan, Stephen Q Wong, Maria Joao Silva, Ravikiran Vedururu, Kenneth Doig, Enid Lam, Gisela Mir Arnau, Timothy Semple, Meaghan Wall, Andjelija Zivanovic, Rishu Agarwal, Pasquale Petrone, Kate Jones, David Westerman, Piers Blombery, John F Seymour, Anthony T Papenfuss, Mark A Dawson, Constantine S Tam, Sarah-Jane Dawson
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28302468/spectroscopic-electrochemical-and-molecular-docking-study-of-the-binding-interaction-of-a-small-molecule-5h-naptho-2-1-f-1-2-oxathieaphine-2-2-dioxide-with-calf-thymus-dna
#3
Abhijit Mukherjee, Shovan Mondal, Bula Singh
The interaction of 5H-naptho[2,1-f][1,2]oxathieaphine2,2-dioxide (NOTD) with calf thymus DNA in Tris-HCl buffer at physiological pH was investigated with the help of various spectroscopic and electrochemical methods along with molecular docking study. Studying the non-covalent binding interaction of a neutral fluorophore with ctDNA has become an active field of research at the interface between medicinal chemistry and biological science. NOTD is known for its various toxicological, skin sensitization, and antiviral properties...
March 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28285684/dual-occurrence-of-alk-g1202r-solvent-front-mutation-and-small-cell-lung-cancer-transformation-as-resistance-mechanisms-to-second-generation-alk-inhibitors-without-prior-exposure-to-crizotinib-pitfall-of-solely-relying-on-liquid-re-biopsy
#4
Sai-Hong Ignatius Ou, Thomas K Lee, Lauren Young, Maria Y Fernandez-Rocha, Dean Pavlick, Alexa B Schrock, Viola W Zhu, Jeffrey Milliken, Siraj M Ali, Barbara J Gitlitz
Development of the acquired ALK G1202R solvent front mutation and small cell lung cancer (SCLC) transformation have both been independently reported as resistance mechanisms to ALK inhibitors in ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients but have not been reported in the same patient. Here we report an ALK+ NSCLC patient who had disease progression after ceritinib and then alectinib where an ALK G1202R mutation was detected on circulating tumor (ct) DNA prior to enrollment onto a trial of another next generation ALK inhibitor, lorlatinib...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28276503/ultrasensitive-colorimetric-detection-of-circulating-tumor-dna-using-hybridization-chain-reaction-and-the-pivot-of-triplex-dna
#5
Ruimin Li, Li Zou, Yanwei Luo, Manjun Zhang, Liansheng Ling
This work presents an amplified colorimetric biosensor for circulating tumor DNA (ctDNA), which associates the hybridization chain reaction (HCR) amplification with G-Quadruplex DNAzymes activity through triplex DNA formation. In the presence of ctDNA, HCR occurs. The resulting HCR products are specially recognized by one sequence to include one GGG repeat and the other containing three GGG repeats, through the synergetic effect of triplex DNA and asymmetrically split G-Quadruplex forming. Such design takes advantage of the amplification property of HCR and the high peroxidase-like catalytic activity of asymmetrically split G-Quadruplex DNAzymes by means of triplex DNA formation, which produces color signals in the presence of ctDNA...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28259999/clinical-and-molecular-assessment-of-regorafenib-monotherapy
#6
Nao Kakizawa, Koichi Suzuki, Taro Fukui, Yuji Takayama, Kosuke Ichida, Yuta Muto, Fumi Hasegawa, Fumiaki Watanabe, Rina Kikugawa, Shingo Tsujinaka, Kazushige Futsuhara, Yasuyuki Miyakura, Hiroshi Noda, Toshiki Rikiyama
Regorafenib has shown survival benefits in metastatic colorectal cancer patients who were exacerbated after all standard therapies. Some patients, however, exhibit severe adverse events (AEs) resulting in treatment discontinuation. Therefore, the selection of patients likely to benefit from regorafenib is crucial. Twenty patients were treated with regorafenib for metastatic colorectal cancer; 122 plasma samples were taken from 16 of these patients for monitoring of circulating tumor DNA (ctDNA) in the blood...
February 15, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259476/treatment-outcomes-and-tumor-loss-of-heterozygosity-in-germline-dna-repair-deficient-prostate-cancer
#7
Matti Annala, Werner J Struss, Evan W Warner, Kevin Beja, Gillian Vandekerkhove, Amanda Wong, Daniel Khalaf, Irma-Liisa Seppälä, Alan So, Gregory Lo, Rahul Aggarwal, Eric J Small, Matti Nykter, Martin E Gleave, Kim N Chi, Alexander W Wyatt
BACKGROUND: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to androgen receptor (AR)-directed therapy. OBJECTIVE: To determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies and to establish whether biallelic DNA repair gene loss is detectable in matched circulating tumor DNA (ctDNA)...
March 1, 2017: European Urology
https://www.readbyqxmd.com/read/28252003/integrating-liquid-biopsies-into-the-management-of-cancer
#8
REVIEW
Giulia Siravegna, Silvia Marsoni, Salvatore Siena, Alberto Bardelli
During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly...
March 2, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28243130/effectiveness-of-circulating-tumor-dna-for-detection-of-kras-gene-mutations-in-colorectal-cancer-patients-a-meta-analysis
#9
Yi-Xin Hao, Qiang Fu, Yan-Yan Guo, Ming Ye, Hui-Xia Zhao, Qi Wang, Xiu-Mei Peng, Qiu-Wen Li, Ru-Liang Wang, Wen-Hua Xiao
Circulating tumor DNA (ctDNA) can be identified in the peripheral blood of patients and harbors the genomic alterations found in tumor tissues, which provides a noninvasive approach for detection of gene mutations. We conducted this meta-analysis to investigate whether ctDNA can be used for monitoring KRAS gene mutations in colorectal cancer (CRC) patients. Medline, Embase, Cochrane Library and Web of Science were searched for the included eligible studies in English, and data were extracted for statistical analysis according to the numbers of true-positive (TP), true-negative (TN), false-positive (FP) and false-negative (FN) cases...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28240774/early-detection-of-pancreatic-cancer-where-are-we-now-and-where-are-we-going
#10
REVIEW
Bin Zhou, Jian-Wei Xu, Yu-Gang Cheng, Jing-Yue Gao, San-Yuan Hu, Lei Wang, Han-Xiang Zhan
Pancreatic cancer (PC) is one of the most lethal malignancies. Recent studies indicate that patients with incidentally diagnosed PC have better prognosis than those with symptoms and that there is a sufficient window for early detection. However, effective early diagnosis remains difficult and depends mainly on imaging modalities and the development of screening methodologies with highly sensitive and specific biomarkers. This review summarizes recent advances in effective screening for early diagnosis of PC using imaging modalities and novel molecular biomarkers discovered from various "omics" studies including genomics, epigenomics, non-coding RNA, metabonomics, liquid biopsy (CTC, ctDNA and exosomes) and microbiomes, and their use in body fluids (feces, urine, and saliva)...
February 27, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28235605/studies-of-dna-binding-properties-of-lafutidine-as-adjuvant-anticancer-agent-to-calf-thymus-dna-using-multi-spectroscopic-approaches-nmr-relaxation-data-molecular-docking-and-dynamical-simulation
#11
Hongqin Yang, Peixiao Tang, Bin Tang, Yanmei Huang, Jiawei He, Shanshan Li, Hui Li
The interactions between lafutidine (LAF) and calf thymus DNA (ctDNA) have been investigated both experimentally and theoretically. UV-vis absorption studies confirmed that LAF binds to ctDNA through non-covalent interactions. Fluorescence quenching and time-resolved fluorescence spectroscopy studies showed that the binding of LAF with ctDNA occurred through static quenching mechanism, resulting in the formation of a LAF-ctDNA complex. The binding constants (K) of the complex were found to be around 10(3)M(-1) via NMR relaxation rates and fluorescence data, and the calculated thermodynamic parameters indicated that hydrogen bonds and van der Waals forces played major roles in the binding of LAF to ctDNA...
February 22, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28225258/nanoparticle-based-discrimination-of-single-nucleotide-polymorphism-in-long-dna-sequences
#12
Maria Sanroman-Iglesias, Charles Lawrie, Luis M Liz-Marzán, Marek Grzelczak
Circulating DNA (ctDNA) and specifically the detection cancer-associated mutations in liquid biopsies promises to revolutionize cancer detection. The main difficulty however is that the length of typical ctDNA fragments (~150 bases) can form secondary structures potentially obscuring the mutated fragment from detection. We show that an assay based on gold nanoparticles (65 nm) stabilized with DNA (Au@DNA) can discriminate single nucleotide polymorphism in clinically-relevant DNA sequences (70-140 bases). The preincubation step was crucial to this process, allowing sequential bridging of Au@DNA, so that single base mutation can be discriminated, down to 100 pM concentration...
February 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28214514/detecting-circulating-tumor-dna-in-renal-cancer-an-open-challenge
#13
Claudia Corrò, Tomas Hejhal, Cédric Poyet, Tullio Sulser, Thomas Hermanns, Thomas Winder, Gerald Prager, Peter J Wild, Ian Frew, Holger Moch, Markus Rechsteiner
BACKGROUND: Detection of circulating tumor DNA (ctDNA) in blood of cancer patients is regarded as an important step towards personalized medicine and treatment monitoring. In the present study, we investigated the clinical applicability of ctDNA as liquid biopsy in renal cancer. METHODS: ctDNA in serum and plasma samples derived from ccRCC and colon cancer patients as well as ctDNA isolated from RCC xenografts with known VHL mutation status was investigated using next generation sequencing (NGS)...
February 22, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28206954/rassf1a-promoter-methylation-in-high-grade-serous-ovarian-cancer-a-direct-comparison-study-in-primary-tumors-adjacent-morphologically-tumor-cell-free-tissues-and-paired-circulating-tumor-dna
#14
Lydia Giannopoulou, Issam Chebouti, Kitty Pavlakis, Sabine Kasimir-Bauer, Evi S Lianidou
The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205231/analysis-of-ctdna-to-predict-prognosis-and-monitor-treatment-responses-in-metastatic-pancreatic-cancer-patients
#15
He Cheng, Chen Liu, Jiahao Jiang, Guopei Luo, Yu Lu, Kaizhou Jin, Meng Guo, Zhenzhen Zhang, Jin Xu, Liang Liu, Quanxing Ni, Xianjun Yu
Cell-free circulating tumor DNA (ctDNA) in plasma has been used as a potential noninvasive biomarker for various tumors. The current study was performed to evaluate the clinical implications of ctDNA detection in patients with metastatic pancreatic cancer. Firstly, we attempted to prospectively screen a panel of 60 genes in cell-free DNA (cfDNA) from ten metastatic pancreatic cancer patients via exome sequencing. Secondly, droplet digital PCR (ddPCR) was used to identify potential mutations in a cohort of 188 patients with metastatic pancreatic cancer...
February 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28187169/prognostic-value-of-circulating-tumor-dna-in-patients-with-colon-cancer-systematic-review
#16
Gaowei Fan, Kuo Zhang, Xin Yang, Jiansheng Ding, Zujian Wang, Jinming Li
The application of circulating tumor DNA(ctDNA) represents a non-invasive method for tumor detection. Its prognostic significance in patients with colorectal cancer is controversial. We performed a systematic review of data from published studies to assess the prognostic values of ctDNA in patients with colorectal cancer. We searched Medline, Embase, Web of Science, the Cochrane Library, and Scopus databases to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to December 6, 2016...
2017: PloS One
https://www.readbyqxmd.com/read/28185687/circulating-tumor-cells-and-circulating-tumor-dna-what-surgical-oncologists-need-to-know
#17
REVIEW
L Cabel, C Proudhon, P Mariani, D Tzanis, G Beinse, I Bieche, J-Y Pierga, F-C Bidard
As a result of recent progress in detection techniques, circulating tumor DNA (ctDNA) and circulating tumor cells (CTC) can now be accurately detected in the blood of most cancer patients. While these new biomarkers can provide a better understanding of key biological mechanisms underlying cancer growth and dissemination, they also open up a wide range of possible clinical applications in medical oncology, radiation oncology and surgical oncology. In this review, we summarize the results obtained with ctDNA and CTC together with their potential future clinical applications in the field of surgical oncology, with particular focus on the perioperative setting of various types of cancer...
January 29, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28164427/application-of-circulating-tumor-dna-in-prospective-clinical-oncology-trials-standardization-of-preanalytical-conditions
#18
Lisanne F van Dessel, Nick Beije, Jean C A Helmijr, Silvia R Vitale, Jaco Kraan, Maxime P Look, Ronald de Wit, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens, Martijn P Lolkema
Circulating tumor DNA (ctDNA) has emerged as a potential new biomarker with diagnostic, predictive, and prognostic applications for various solid tumor types. Before beginning large prospective clinical trials to prove the added value of utilizing ctDNA in clinical practice, it is essential to investigate the effects of various preanalytical conditions on the quality of cell-free DNA (cfDNA) in general and of ctDNA in particular in order to optimize and standardize these conditions. Whole blood samples were collected from patients with metastatic cancer bearing a known somatic variant...
February 6, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28164088/effective-implementation-of-novel-met-pharmacodynamic-assays-in-translational-studies
#19
REVIEW
Apurva K Srivastava, Tony Navas, William G Herrick, Melinda G Hollingshead, Donald P Bottaro, James H Doroshow, Ralph E Parchment
MET tyrosine kinase (TK) dysregulation is significantly implicated in many types of cancer. Despite over 20 years of drug development to target MET in cancers, a pure anti-MET therapeutic has not yet received market approval. The failure of two recently concluded phase III trials point to a major weakness in biomarker strategies to identify patients who will benefit most from MET therapies. The capability to interrogate oncogenic mutations in MET via circulating tumor DNA (ctDNA) provides an important advancement in identification and stratification of patients for MET therapy...
January 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28162206/-hot-topics-of-circulating-tumor-dna-testing-in-breast-cancer
#20
Y H Liu, B Zhou, L Xu, L Xin
The progress of gene detection technologies represented by next generation sequencing (NGS) and digital PCR laid a foundation for studies of circulating tumor DNA (ctDNA) in breast cancer. In 2014, the NGS workgroup organized by the College of American Pathologists (CAP) published the College of American Pathologists' Laboratory Standards for Next-Generation Sequencing Clinical Tests, which provides a blueprint for the standardization of gene testing. In 2015, the Guidelines for Diagnostic Next-generation Sequencing published by the European Society of Human Genetics claimed that NGS is unacceptable in clinical practice before studies guided by guidelines are approved...
February 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
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