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https://www.readbyqxmd.com/read/28238819/alkylphospholipids-an-update-on-molecular-mechanisms-and-clinical-relevance
#1
REVIEW
Pablo Ríos-Marco, Carmen Marco, Xiomara Gálvez, Jose M Jiménez-López, María P Carrasco
Alkylphospholipid (APL) represent a new class of drugs which do not interact directly with DNA but act on the cell membrane where they accumulate and interfere with lipid metabolism and signalling pathways. This review summarizes the mode of action at the molecular level of these compounds. In this sense, a diversity of mechanisms has been suggested to explain the actions of clinically-relevant APLs, in particular, in cancer treatment. One consistently reported finding is that APLs reduce the biosynthesis of phosphatidylcholine (PC) by inhibiting the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CT)...
February 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28194229/circulating-and-tissue-biomarkers-in-early-stage-non-small-cell-lung-cancer
#2
Caterina Fumagalli, Fabrizio Bianchi, Paola Rafaniello Raviele, Davide Vacirca, Giovanni Bertalot, Cristiano Rampinelli, Matteo Lazzeroni, Bernardo Bonanni, Giulia Veronesi, Nicola Fusco, Massimo Barberis, Elena Guerini-Rocco
OBJECTIVE: We sought to characterise circulating and tissue tumour biomarkers of patients who developed early-stage non-small cell lung cancer (NSCLC) during long-term follow-up of a chemoprevention trial (NCT00321893). MATERIALS AND METHODS: Blood and sputum samples were collected from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Baseline serum was investigated with a previously validated test based on 13 circulating miRNAs (miR-Test)...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28183140/correlation-between-pik3ca-mutations-in-cell-free-dna-and-everolimus-efficacy-in-hr-her2-advanced-breast-cancer-results-from-bolero-2
#3
Mary Ellen Moynahan, David Chen, Wei He, Patricia Sung, Aliaksandra Samoila, Daoqi You, Trusha Bhatt, Parul Patel, Francois Ringeisen, Gabriel N Hortobagyi, Jose Baselga, Sarat Chandarlapaty
BACKGROUND: The current analysis was performed to evaluate the impact of PIK3CA hotspot mutations on everolimus efficacy in BOLERO-2 participants, using cell-free DNA (cfDNA) from plasma samples collected at the time of patient randomisation. METHODS: PIK3CA H1047R, E545K, and E542K mutations in plasma-derived cfDNA were analysed by droplet digital PCR (ddPCR). Median PFS was estimated for patient subgroups defined by PIK3CA mutations in each treatment arm. RESULTS: Among 550 patients included in cfDNA analysis, median PFS in everolimus vs placebo arms was similar in patients with tumours that had wild-type or mutant PIK3CA (hazard ratio (HR), 0...
February 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28170370/development-of-a-gene-panel-for-next-generation-sequencing-of-clinically-relevant-mutations-in-cell-free-dna-from-cancer-patients
#4
Umberto Malapelle, Clara Mayo de-Las-Casas, Danilo Rocco, Monica Garzon, Pasquale Pisapia, Nuria Jordana-Ariza, Maria Russo, Roberta Sgariglia, Caterina De Luca, Francesco Pepe, Alejandro Martinez-Bueno, Daniela Morales-Espinosa, María González-Cao, Niki Karachaliou, Santiago Viteri Ramirez, Claudio Bellevicine, Miguel Angel Molina-Vila, Rafael Rosell, Giancarlo Troncone
BACKGROUND: When tumour tissue is unavailable, cell-free DNA (cfDNA)can serve as a surrogate for genetic analyses. Because mutated alleles in cfDNA are usually below 1%, next-generation sequencing (NGS)must be narrowed to target only clinically relevant genes. In this proof-of-concept study, we developed a panel to use in ultra-deep sequencing to identify such mutations in cfDNA. METHODS: Our panel ('SiRe') covers 568 mutations in six genes (EGFR, KRAS, NRAS, BRAF, cKIT and PDGFRα)involved in non-small-cell lung cancer (NSCLC), gastrointestinal stromal tumour, colorectal carcinoma and melanoma...
February 7, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28126926/molecular-disease-monitoring-using-circulating-tumor-dna-in-myelodysplastic-syndromes
#5
Paul Yeh, Michael Dickinson, Sarah Ftouni, Tane Hunter, Devbarna Sinha, Stephen Q Wong, Rishu Agarwal, Ravikiran Vedururu, Kenneth Doig, Chun Yew Fong, Piers Blombery, David Westerman, Mark A Dawson, Sarah-Jane Dawson
The diagnosis and monitoring of myelodysplastic syndromes (MDS) are highly reliant on bone marrow morphology, which is associated with substantial inter-observer variability. Azacitidine is the mainstay of treatment in MDS, however only half of all patients respond. Therefore, there is an urgent need for improved modalities for the diagnosis and monitoring of MDS. The majority of MDS patients have either clonal somatic karyotypic abnormalities and/or gene mutations that aid in the diagnosis and can be used to monitor treatment response...
January 26, 2017: Blood
https://www.readbyqxmd.com/read/28105346/human-papillomavirus-is-a-favourable-prognostic-factor-in-cancer-of-unknown-primary-in-the-head-and-neck-region-and-in-hypopharyngeal-cancer
#6
Lars Sivars, Cinzia Bersani, Nathalie Grün, Torbjörn Ramqvist, Eva Munck-Wikland, Christian Von Buchwald, Tina Dalianis
Human papillomavirus (HPV), in addition to smoking and alcohol, is a cause of oropharyngeal squamous cell carcinoma (OPSCC), particularly of the tonsils and base of the tongue (TSCC and BOTSCC, respectively). Moreover, HPV-positive TSCC and BOTSCC are associated with a better outcome compared with their HPV-negative counterparts (80 vs. 40% 3-year disease-free survival rate, respectively) and their incidence has increased in several countries. Recently, accumulating evidence of HPV in a considerable proportion of cancers of unknown primary (CUP) in the head and neck region and in a small proportion of hypopharyngeal SCCs has been reported...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28104619/osimertinib-benefit-in-egfr-mutant-nsclc-patients-with-t790m-mutation-detected-by-circulating-tumour-dna
#7
J Remon, C Caramella, C Jovelet, L Lacroix, A Lawson, S Smalley, K Howarth, D Gale, E Green, V Plagnol, N Rosenfeld, D Planchard, M V Bluthgen, A Gazzah, C Pannet, C Nicotra, E Auclin, J C Soria, B Besse
BACKGROUND: Approximately 50% of Epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. MATERIAL AND METHODS: ctDNA T790M mutational status was assessed by Inivata InVision(TM) (eTAm-Seq(TM)) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016...
January 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28104311/comprehensive-profiling-of-the-androgen-receptor-in-liquid-biopsies-from-castration-resistant-prostate-cancer-reveals-novel-intra-ar-structural-variation-and-splice-variant-expression-patterns
#8
Bram De Laere, Pieter-Jan van Dam, Tom Whitington, Markus Mayrhofer, Emanuela Henao Diaz, Gert Van den Eynden, Jean Vandebroek, Jurgen Del-Favero, Steven Van Laere, Luc Dirix, Henrik Grönberg, Johan Lindberg
BACKGROUND: Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). However, a large fraction of nonresponding patients are AR-V7-negative. OBJECTIVE: To investigate if a comprehensive liquid biopsy-based AR profile may improve patient stratification in the context of second-line endocrine therapy. DESIGN, SETTING, AND PARTICIPANTS: Peripheral blood was collected from patients with CRPC (n=30) before initiation of a new line of systemic therapy...
January 16, 2017: European Urology
https://www.readbyqxmd.com/read/28096542/liquid-biopsy-in-2016-circulating-tumour-cells-and-cell-free-dna-in-gastrointestinal-cancer
#9
Klaus Pantel, Catherine Alix-Panabières
No abstract text is available yet for this article.
February 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28072763/epithelial-to-mesenchymal-transition-and-hpv-infection-in-squamous-cell-oropharyngeal-carcinomas-the-papillophar-study
#10
Marine Lefevre, Alexandra Rousseau, Thomas Rayon, Véronique Dalstein, Christine Clavel, Agnès Beby-Defaux, Jean-Luc Pretet, Patrick Soussan, Myriam Polette, Jean Lacau Saint Guily, Philippe Birembaut
BACKGROUND: Human Papillomavirus (HPV) infection is recognised as aetiological factor of carcinogenesis in oropharyngeal squamous cell carcinomas (OPC). HPV-related OPC respond better to treatments and have a significantly favourable outcome. Epithelial to mesenchymal transition (EMT) implicated in tumour invasion, is a hallmark of a poor prognosis in carcinomas. METHODS: We have studied the relationship of EMT markers (E-cadherin, β-catenin and vimentin) with HPV infection (DNA and E6/E7 mRNA detection), p16(INK4a) expression and survival outcomes in a cohort of 296 patients with OPC...
January 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28061772/use-of-liquid-biopsies-to-monitor-disease-progression-in-a-sarcoma-patient-a-case-report
#11
Heidi M Namløs, Olga Zaikova, Bodil Bjerkehagen, Daniel Vodák, Eivind Hovig, Ola Myklebost, Kjetil Boye, Leonardo A Meza-Zepeda
BACKGROUND: Many patients experience local recurrence or metastases after receiving potentially curative treatment, and early detection of these events is important for disease control. Recent technological advances make it possible to use blood plasma containing circulating cell-free tumour DNA (ctDNA) as a liquid biopsy. In this case report we show how serial liquid biopsies can be used to monitor the disease course and detect disease recurrence in a sarcoma patient. CASE PRESENTATION: A 55-year-old male presented with a rapidly growing, painful palpable mass in the left groin region, and a biopsy revealed a high-grade malignant spindle cell sarcoma...
January 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28006816/egfr-mutation-detection-in-circulating-cell-free-dna-of-lung-adenocarcinoma-patients-analysis-of-lux-lung-3-and-6
#12
Yi-Long Wu, Lecia V Sequist, Cheng-Ping Hu, Jifeng Feng, Shun Lu, Yunchao Huang, Wei Li, Mei Hou, Martin Schuler, Tony Mok, Nobuyuki Yamamoto, Kenneth O'Byrne, Vera Hirsh, Neil Gibson, Dan Massey, Miyoung Kim, James Chih-Hsin Yang
BACKGROUND: In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+). METHODS: Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-time PCR kit...
January 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/27997582/-gt-n-repeat-polymorphism-in-heme-oxygenase-1-ho-1-correlates-with-clinical-outcome-after-myeloablative-or-nonmyeloablative-allogeneic-hematopoietic-cell-transplantation
#13
Tania Køllgaard, Brian Kornblit, Jesper Petersen, Tobias Wirenfeldt Klausen, Bo Kok Mortensen, Peter Brændstrup, Henrik Sengeløv, Estrid Høgdall, Klaus Müller, Lars Vindeløv, Mads Hald Andersen, Per Thor Straten
Allogeneic hematopoietic cell transplantation (HCT) is a treatment for various hematologic diseases where efficacy of treatment is in part based on the graft versus tumour (GVT) activity of cells in the transplant. The cytoprotective enzyme heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation and it has been shown to exert anti-inflammatory functions. In humans a (GT)n repeat polymorphism regulates the expression of HO-1. We conducted fragment length analyses of the (GT)n repeat in the promotor region of the gene for HO-1 in DNA from donors and recipients receiving allogeneic myeloablative- (MA) (n = 110) or nonmyeloablative- (NMA-) (n = 250) HCT...
2016: PloS One
https://www.readbyqxmd.com/read/27994225/comparison-of-circulating-tumour-cells-and-circulating-cell-free-epstein-barr-virus-dna-in-patients-with-nasopharyngeal-carcinoma-undergoing-radiotherapy
#14
Jess Honganh Vo, Wen Long Nei, Min Hu, Wai Min Phyo, Fuqiang Wang, Kam Weng Fong, Terence Tan, Yoke Lim Soong, Shie Lee Cheah, Kiattisa Sommat, Huiyu Low, Belinda Ling, Johnson Ng, Wan Loo Tan, Kian Sing Chan, Lynette Oon, Jackie Y Ying, Min-Han Tan
Quantification of Epstein-Barr virus (EBV) cell-free DNA (cfDNA) is commonly used in clinical settings as a circulating biomarker in nasopharyngeal carcinoma (NPC), but there has been no comparison with circulating tumour cells (CTCs). Our study aims to compare the performance of CTC enumeration against EBV cfDNA quantitation through digital PCR (dPCR) and quantitative PCR. 74 plasma samples from 46 NPC patients at baseline and one month after radiotherapy with or without concurrent chemotherapy were analysed...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27983717/evaluation-of-methylation-biomarkers-for-detection-of-circulating-tumor-dna-and-application-to-colorectal-cancer
#15
Susan M Mitchell, Thu Ho, Glenn S Brown, Rohan T Baker, Melissa L Thomas, Aidan McEvoy, Zheng-Zhou Xu, Jason P Ross, Trevor J Lockett, Graeme P Young, Lawrence C LaPointe, Susanne K Pedersen, Peter L Molloy
Solid tumors shed DNA into circulation, and there is growing evidence that the detection of circulating tumor DNA (ctDNA) has broad clinical utility, including monitoring of disease, prognosis, response to chemotherapy and tracking tumor heterogeneity. The appearance of ctDNA in the circulating cell-free DNA (ccfDNA) isolated from plasma or serum is commonly detected by identifying tumor-specific features such as insertions, deletions, mutations and/or aberrant methylation. Methylation is a normal cell regulatory event, and since the majority of ccfDNA is derived from white blood cells (WBC), it is important that tumour-specific DNA methylation markers show rare to no methylation events in WBC DNA...
December 15, 2016: Genes
https://www.readbyqxmd.com/read/27959945/the-in-vitro-stability-of-circulating-tumour-dna
#16
Emanuela Henao Diaz, Jeffrey Yachnin, Henrik Grönberg, Johan Lindberg
OBJECTIVE: DNA from apoptotic cancer cells, present in the circulation, has the potential to facilitate genomic profiling and disease monitoring. However, only low fractions of total cell-free DNA originates from cancer cells, limiting the applicability of circulating tumour DNA (ctDNA). Optimal sample processing is consequently of uttermost importance. Therefore, we evaluated the in vitro stability of ctDNA. EXPERIMENTAL DESIGN: Blood was collected in 10 ml EDTA or Streck tubes...
2016: PloS One
https://www.readbyqxmd.com/read/27942391/metastatic-basal-cell-carcinoma-with-amplification-of-pd-l1-exceptional-response-to-anti-pd1-therapy
#17
Sadakatsu Ikeda, Aaron M Goodman, Philip R Cohen, Taylor J Jensen, Christopher K Ellison, Garrett Frampton, Vincent Miller, Sandip P Patel, Razelle Kurzrock
Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA)...
2016: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/27929064/acquired-ras-or-egfr-mutations-and-duration-of-response-to-egfr-blockade-in-colorectal-cancer
#18
Beth O Van Emburgh, Sabrina Arena, Giulia Siravegna, Luca Lazzari, Giovanni Crisafulli, Giorgio Corti, Benedetta Mussolin, Federica Baldi, Michela Buscarino, Alice Bartolini, Emanuele Valtorta, Joana Vidal, Beatriz Bellosillo, Giovanni Germano, Filippo Pietrantonio, Agostino Ponzetti, Joan Albanell, Salvatore Siena, Andrea Sartore-Bianchi, Federica Di Nicolantonio, Clara Montagut, Alberto Bardelli
Blockade of the epidermal growth factor receptor (EGFR) with the monoclonal antibodies cetuximab or panitumumab is effective in a subset of colorectal cancers (CRCs), but the emergence of resistance limits the efficacy of these therapeutic agents. At relapse, the majority of patients develop RAS mutations, while a subset acquires EGFR extracellular domain (ECD) mutations. Here we find that patients who experience greater and longer responses to EGFR blockade preferentially develop EGFR ECD mutations, while RAS mutations emerge more frequently in patients with smaller tumour shrinkage and shorter progression-free survival...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27903276/accurate-prediction-of-response-to-endocrine-therapy-in-breast-cancer-patients-current-and-future-biomarkers
#19
REVIEW
Cigdem Selli, J Michael Dixon, Andrew H Sims
Approximately 70% of patients have breast cancers that are oestrogen receptor alpha positive (ER+) and are therefore candidates for endocrine treatment. Many of these patients relapse in the years during or following completion of adjuvant endocrine therapy. Thus, many ER+ cancers have primary resistance or develop resistance to endocrine therapy during treatment. Recent improvements in our understanding of how tumours evolve during treatment with endocrine agents have identified both changes in gene expression and mutational profiles, in the primary cancer as well as in circulating tumour cells...
December 1, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27902986/the-presence-of-hpv-dna-in-neck-lymph-node-metastasis-correlates-with-improved-overall-survival-of-patients-with-oropharyngeal-cancer-undergoing-surgical-treatment
#20
Eiji Shimura, Takanori Hama, Toshihito Suda, Masahiro Ikegami, Mitsuyoshi Urashima, Hiromi Kojima
BACKGROUND: Few studies have addressed how human papilloma virus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) affects the outcome of surgical therapy; furthermore, the relationship between the presence of HPV DNA and neck lymph node (LN) metastasis has not been well established. METHODS: A total of 65 patients who underwent surgery as a first-line therapy for OPSCC were enrolled in this study. In HPV-positive patients, the presence of HPV DNA in metastatic neck LN lesions was evaluated...
2017: Oncology
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