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Johannes Fredebohm, Daniel H Mehnert, Ann-Kathrin Löber, Frank Holtrup, Vanessa van Rahden, Philipp Angenendt, Frank Diehl
We have designed a highly sensitive assay based on the Safe-SeqS technology to detect de novo mutations in the KIT gene and tested its performance. This assay was applied to plasma samples of GIST patients before and after treatment with regorafenib (GRID III trial) and mutations at known and novel sites of potential secondary resistance were identified.
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
Hongdo Do, Daniel Cameron, Ramyar Molania, Bibhusal Thapa, Gareth Rivalland, Paul L Mitchell, Carmel Murone, Thomas John, Anthony Papenfuss, Alexander Dobrovic
Identifying circulating tumour DNA (ctDNA) for monitoring of cancer therapy is dependent on the development of readily designed, sensitive cancer-specific DNA markers. Genomic rearrangements that are present in the vast majority of cancers provide such markers.Tumour DNA isolated from two fresh-frozen lung tumours underwent whole genome sequencing. Genomic rearrangements were detected using a new computational algorithm, GRIDSS. Four genomic rearrangements from each tumour were chosen for further study using rearrangement-specific primers...
2016: Advances in Experimental Medicine and Biology
Elena Trujillo-Arribas, Hada C Macher, Pilar Jiménez-Arriscado, Fernando de la Portilla, Patrocinio Molinero, Juan M Guerrero, Amalia Rubio
Genomic characterization of cell-free circulating tumour DNA (ctDNA) may offer an opportunity to assess clonal dynamics throughout the course of a patient's illness. The existence of KRAS driver mutations in colon cancer patients is determinant to decide their treatment and to predict their outcome. DNA is extracted automatically from 400 μL of serum using the MagNa Pure Compact with the Nucleic Acid Isolation Kit I. DNA amplification, COLD-PCR and HRM were performed in the same run in the Light Cycler 480...
2016: Advances in Experimental Medicine and Biology
Jason Zhu, John H Strickler
"Liquid biopsies" are blood based assays used to detect and analyze circulating tumor products, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating messenger RNA (mRNA), circulating microRNA (miRNA), circulating exosomes, and tumor educated platelets (TEP). For patients with gastrointestinal (GI) malignancies, blood based biopsies may offer several advantages. First, tumor tissue samples are often challenging to procure, and when obtainable, are often insufficient for genomic profiling...
October 2016: Journal of Gastrointestinal Oncology
Na Zhou, Cong Min Liu, He Lei Hou, Chuan Tao Zhang, Dong Liu, Guan Qun Wang, Ke Wei Liu, Jing Juan Zhu, Hong Ying Lv, Tian Jun Li, Xiaochun Zhang
Spindle cell carcinoma of the breast is a rare subtype of metaplastic carcinoma, and no effective chemotherapy special for metaplastic carcinoma exists until now. As spindle cell carcinomas of the breast are typically "Triple Negative", endocrine therapy and molecular therapy targeted to Her2 might not be favorable, resulting in poor prognosis. Apatinib is currently being tested in patients with breast or lung cancers. Here we report a successful case using Apatinib to treat spindle cell carcinoma of breast...
October 11, 2016: Oncotarget
Hongjuan Zhao, Rosalie Nolley, Andy M W Chan, Erinn B Rankin, Donna M Peehl
MET plays an important role in the development and progression of papillary renal cell carcinoma (pRCC). Evaluation of efficacy of MET inhibitors against pRCC has been hampered by limited preclinical models depicting MET abnormalities. We established a new patient-derived xenograft (PDX) model of pRCC carrying an activating mutation of MET and tested the ability of cabozantinib, an inhibitor of receptor tyrosine kinases including MET, to inhibit tumor growth and metastasis. Precision-cut, thin tissue slices from a pRCC specimen obtained by nephrectomy were implanted under the renal capsule of RAG2(-/-)γC(-/-) mice to establish first generation TSG-RCC-030...
August 11, 2016: Cancer Biology & Therapy
T Cifuentes, J Cayupi, C Celis-Barros, G Zapata-Torres, Rafael Ballesteros, Rafael Ballesteros-Garrido, B Abarca, C Jullian
The inclusion complexation behavior of 3-(2-thienyl)-[1,2,3]triazolo[1,5-a] pyridine (TTP) with native β-cyclodextrin and derivatized cyclodextrins was investigated. Stability constants for complexes with 1 : 1 molar ratios were calculated from phase solubility diagrams. The solubilizing efficiency of the TTP inclusion complex is enhanced in the order of DMβCD > HPβCD > βCD. The TTP-DMβCD inclusion complex was further characterized in solution by means of absorption, fluorescence, 2D NMR and molecular modeling methods...
October 18, 2016: Organic & Biomolecular Chemistry
Kohei Shitara, Kimio Yonesaka, Tadamichi Denda, Kentaro Yamazaki, Toshikazu Moriwaki, Masahiro Tsuda, Toshimi Takano, Hiroyuki Okuda, Tomohiro Nishina, Kazuko Sakai, Kazuto Nishio, Shoji Tokunaga, Takeharu Yamanaka, Narikazu Boku, Ichinosuke Hyodo, Kei Muro
This randomized phase II trial compared panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) with bevacizumab plus FOLFIRI as second-line chemotherapy for wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) and to explore the values of oncogenes in circulating tumor DNA (ctDNA) and serum proteins as predictive biomarkers. Patients with WT KRAS exon 2 mCRC refractory to first-line chemotherapy containing oxaliplatin and bevacizumab were randomly assigned to panitumumab plus FOLFIRI or bevacizumab plus FOLFIRI...
October 6, 2016: Cancer Science
Alex F Herrera, Haesook T Kim, Katherine A Kong, Malek Faham, Heather Sun, Aliyah R Sohani, Edwin P Alyea, Victoria E Carlton, Yi-Bin Chen, Corey S Cutler, Vincent T Ho, John Koreth, Chitra Kotwaliwale, Sarah Nikiforow, Jerome Ritz, Scott J Rodig, Robert J Soiffer, Joseph H Antin, Philippe Armand
Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes...
October 6, 2016: British Journal of Haematology
Fumio Imamura, Junji Uchida, Yoji Kukita, Toru Kumagai, Kazumi Nishino, Takako Inoue, Madoka Kimura, Kikuya Kato
OBJECTIVES: Early evaluation of the effect of treatment is helpful in the management of cancer patients. Circulating biomarkers are an ideal tool for this if they are highly specific to tumors and respond rapidly to tumor volume changes. Circulating tumor DNA (ctDNA) is one such candidate. We conducted a prospective study to test the utility of EGFR ctDNA in early evaluation of EGFR-TKI effects. RESULTS: Twenty-one patients with EGFR-mutant lung cancer who were naïve to EGFR-TKI were enrolled...
September 30, 2016: Oncotarget
Ao Huang, Xin Zhang, Shao-Lai Zhou, Ya Cao, Xiao-Wu Huang, Jia Fan, Xin-Rong Yang, Jian Zhou
PURPOSE: Circulating tumor DNA (ctDNA) is increasingly recognized as liquid biopsy to profile tumor genome. Droplet digital PCR (ddPCR) is a highly sensitive and easily operable platform for mutant detection. Here, we tried to detect ctDNA in hepatocellular carcinoma (HCC) patients using ddPCR. METHODS: Studies sequencing the genome of HCCs and COSMIC (Catalogue of Somatic Mutations in Cancer) database were reviewed to identify hotspot mutations. Circulating cell-free DNAs (cfDNAs) extracted from 1 ml preoperative plasma sample were analyzed to detect circulating mutants using ddPCR...
2016: Journal of Cancer
Fariz Nurwidya, Jamal Zaini, Andika Chandra Putra, Sita Andarini, Achmad Hudoyo, Elisna Syahruddin, Faisal Yunus
Circulating tumor cells (CTCs) are tumor cells that are separated from the primary site or metastatic lesion and disseminate in blood circulation. CTCs are considered to be part of the long process of cancer metastasis. As a 'liquid biopsy', CTC molecular examination and investigation of single cancer cells create an important opportunity for providing an understanding of cancer biology and the process of metastasis. In the last decade, we have seen dramatic development in defining the role of CTCs in lung cancer in terms of diagnosis, genomic alteration determination, treatment response and, finally, prognosis prediction...
September 2016: Chonnam Medical Journal
Stephan M Feller, Marc Lewitzky
Non-protein coding RNAs in different flavors (miRNAs, piRNAs, snoRNAs, lncRNAs, SHOT-RNAs), exosomes, large oncosomes, exoDNA and now tumor-educated platelets (TEPs) have emerged as crucial signal transmitting, transporting and regulating devices of cells in the last two decades. They are also establishing themselves increasingly in the realm of tumor research. We are currently witnessing a mushrooming of candidate entities for diagnostic and prognostic cancer detection and characterization tests that could have a major impact on how this diverse group of diseases is initially spotted and subsequently treated in the near future...
September 27, 2016: Cell Communication and Signaling: CCS
Sai-Hong Ignatius Ou, Lauren Young, Alexa B Schrock, Adrienne Johnson, Samuel J Klempner, Viola W Zhu, Vincent A Miller, Siraj M Ali
INTRODUCTION: MET exon14 skipping (METex14) alterations represent a unique subset of oncogenic drivers in non-small cell lung cancer (NSCLC). Preliminary clinical activity of crizotinib against METex14+ NSCLC has been reported. The full spectrum of resistance mechanisms to crizotinib in METex14+ NSCLC remains to be identified. METHODS: Hybrid-capture based comprehensive genomic profiling (CGP) performed on a tumor specimen obtained at diagnosis and a hybrid capture-based assay of circulating tumor DNA (ctDNA) at the time of progression on crizotinib was assessed in a pairwise fashion...
September 22, 2016: Journal of Thoracic Oncology
Nannan Guo, Feng Lou, Yongfu Ma, Jie Li, Bo Yang, Wei Chen, Hua Ye, Jing-Bo Zhang, Ming-Yu Zhao, Wen-Jun Wu, Rong Shi, Lindsey Jones, Katherine S Chen, Xue F Huang, Si-Yi Chen, Yang Liu
Circulating tumor DNA (ctDNA) in peripheral blood is a "liquid biopsy" that contains representative tumor information including gene mutations. Additionally, repeated ctDNA samples can be easily obtained to monitor response to treatment and disease progression, which may be especially valuable to lung cancer patients with tumors that cannot be easily biopsied or removed. To investigate the changes in ctDNA after surgical tumor resection, tumor and blood samples obtained before and after surgery were collected prospectively from 41 non-small lung cancer (NSCLC) patients...
2016: Scientific Reports
Pamela J Kaisaki, Anthony Cutts, Niko Popitsch, Carme Camps, Melissa M Pentony, Gareth Wilson, Suzanne Page, Kulvinder Kaur, Dimitris Vavoulis, Shirley Henderson, Avinash Gupta, Mark R Middleton, Ioannis Karydis, Denis C Talbot, Anna Schuh, Jenny C Taylor
Use of circulating tumour DNA (ctDNA) as a liquid biopsy has been proposed for potential identification and monitoring of solid tumours. We investigate a next-generation sequencing approach for mutation detection in ctDNA in two related studies using a targeted panel. The first study was retrospective, using blood samples taken from melanoma patients at diverse timepoints before or after treatment, aiming to evaluate correlation between mutations identified in biopsy and ctDNA, and to acquire a first impression of influencing factors...
2016: PloS One
Alexandra R Lewis, Juan W Valle, Mairead G McNamara
Pancreatic cancer is a disease that carries a poor prognosis. Accurate tissue diagnosis is required. Tumours contain a high content of stromal tissue and therefore biopsies may be inconclusive. Circulating tumour cells (CTCs) have been investigated as a potential "liquid biopsy" in several malignancies and have proven to be of prognostic value in breast, prostate and colorectal cancers. They have been detected in patients with localised and metastatic pancreatic cancer with sensitivities ranging from 38%-100% using a variety of platforms...
August 28, 2016: World Journal of Gastroenterology: WJG
Mengjia Qian, Diane C Wang, Hao Chen, Yunfeng Cheng
Single cell heterogeneity has already been highlighted in cancer classification, diagnosis, and treatment. Recent advanced technologies have gained more ability to reveal the heterogeneity on single cell level. In this review, we listed various detection targets applied in single cell study, including tumor tissue cells, circulating tumor cells (CTCs), disseminated tumor cells (DTCs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), and cancer stem cells (CSCs). We further discussed and compared detection methods using these detection targets in different fields to reveal single cell heterogeneity in cancer...
September 13, 2016: Seminars in Cell & Developmental Biology
Andréa P Carnizello, Marília I F Barbosa, Monize Martins, Natália H Ferreira, Pollyanna F Oliveira, Geórgia M Magalhães, Alzir A Batista, Denise C Tavares
This study performed in vitro and in vivo biological assays of the ruthenium (II) compound ct-[RuCl(CO)(dppb)(bipy)]PF6 (where, dppb=1,4-bis(diphenylphosphine)butane and bipy=2,2'-bipyridine). The cytotoxic activity of this compound was evaluated against different tumor cell lines (HeLa, human cervical adenocarcinoma; MCF7, human breast adenocarcinoma; MO59J, human glioblastoma; HepG2, hepatocellular carcinoma and B16F10, murine melanoma) and healthy cell line (V79, Chinese hamster lung fibroblasts), by XTT (sodium 2,3'-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-3,4-tetrazolium-bis(4-methoxy-6-nitro)benzene-sulfonic acid hydrate) method...
August 25, 2016: Journal of Inorganic Biochemistry
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