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https://www.readbyqxmd.com/read/28332571/profiling-protein-expression-in-circulating-tumour-cells-using-microfluidic-western-blotting
#1
Elly Sinkala, Elodie Sollier-Christen, Corinne Renier, Elisabet Rosàs-Canyelles, James Che, Kyra Heirich, Todd A Duncombe, Julea Vlassakis, Kevin A Yamauchi, Haiyan Huang, Stefanie S Jeffrey, Amy E Herr
Circulating tumour cells (CTCs) are rare tumour cells found in the circulatory system of certain cancer patients. The clinical and functional significance of CTCs is still under investigation. Protein profiling of CTCs would complement the recent advances in enumeration, transcriptomic and genomic characterization of these rare cells and help define their characteristics. Here we describe a microfluidic western blot for an eight-plex protein panel for individual CTCs derived from estrogen receptor-positive (ER+) breast cancer patients...
March 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28329770/antigen-presentation-profiling-reveals-recognition-of-lymphoma-immunoglobulin-neoantigens
#2
Michael S Khodadoust, Niclas Olsson, Lisa E Wagar, Ole A W Haabeth, Binbin Chen, Kavya Swaminathan, Keith Rawson, Chih Long Liu, David Steiner, Peder Lund, Samhita Rao, Lichao Zhang, Caleb Marceau, Henning Stehr, Aaron M Newman, Debra K Czerwinski, Victoria E H Carlton, Martin Moorhead, Malek Faham, Holbrook E Kohrt, Jan Carette, Michael R Green, Mark M Davis, Ronald Levy, Joshua E Elias, Ash A Alizadeh
Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. However, the personalized identification and validation of neoantigens remains a major challenge. Here we discover neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically characterize MHC ligands from 17 patients...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28327598/global-dna-methylation-analysis-identifies-two-discrete-clusters-of-pheochromocytoma-with-distinct-genomic-and-genetic-alterations
#3
Samuel Backman, Rajani Maharjan, Alberto Falk-Delgado, Joakim Crona, Kenko Cupisti, Peter Stålberg, Per Hellman, Peyman Björklund
Pheochromocytomas and paragangliomas (PPGLs) are rare and frequently heritable neural-crest derived tumours arising from the adrenal medulla or extra-adrenal chromaffin cells respectively. The majority of PPGL tumours are benign and do not recur with distant metastases. However, a sizeable fraction of these tumours secrete vasoactive catecholamines into the circulation causing a variety of symptoms including hypertension, palpitations and diaphoresis. The genetic landscape of PPGL has been well characterized and more than a dozen genes have been described as recurrently mutated...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322181/epithelial-mesenchymal-and-hybrid-epithelial-mesenchymal-phenotypes-and-their-clinical-relevance-in-cancer-metastasis
#4
Minal Garg
Cancer metastasis occurs through local invasion of circulating tumour cells (CTCs), intravasation, transportation to distant sites, and their extravasation followed by colonisation at secondary sites. Epithelial-mesenchymal transition (EMT) is a normal developmental phenomenon, but its aberrant activation confers tumour cells with enhanced cell motility, metastatic properties, resistant to therapies and cancer stem cell (CSC) phenotype in epithelium-derived carcinoma. Experimental studies from various research papers have been reviewed to determine the factors, which interlink cancer stemness and cellular plasticity with EMT...
March 21, 2017: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/28321147/detection-of-circulating-tumour-cells-in-urothelial-cancers-and-clinical-correlations-comparison-of-two-methods
#5
Emanuela Fina, Andrea Necchi, Stefano Bottelli, Carolina Reduzzi, Sara Pizzamiglio, Chiara Iacona, Maria Grazia Daidone, Paolo Verderio, Vera Cappelletti
Circulating tumour cells (CTC) are identified exploiting their protein/gene expression patterns or distinct size compared to blood cells. Data on CTC in bladder cancer (BC) are still scarce. We comparatively analyzed CTC enrichment by AdnaTest ProstateCancerSelect (AT) and ScreenCell®Cyto (SC) kits, combined with identification by EPCAM, MUC1, and ERBB2 expression and by cytological criteria, respectively, in 19 nonmetastatic (M0) and 47 metastatic (M+) BC patients, at baseline (T0) and during treatment (T1)...
2017: Disease Markers
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#6
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28317839/polymeric-mechanical-amplifiers-of-immune-cytokine-mediated-apoptosis
#7
Michael J Mitchell, Jamie Webster, Amanda Chung, Pedro P G Guimarães, Omar F Khan, Robert Langer
Physical forces affect tumour growth, progression and metastasis. Here, we develop polymeric mechanical amplifiers that exploit in vitro and in vivo physical forces to increase immune cytokine-mediated tumour cell apoptosis. Mechanical amplifiers, consisting of biodegradable polymeric particles tethered to the tumour cell surface via polyethylene glycol linkers, increase the apoptotic effect of an immune cytokine on tumour cells under fluid shear exposure by as much as 50% compared with treatment under static conditions...
March 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28306358/the-genetics-of-gastroesophageal-adenocarcinoma-and-the-use-of-circulating-cell-free-dna-for-disease-detection-and-monitoring
#8
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/28303905/pre-metastatic-niches-organ-specific-homes-for-metastases
#9
REVIEW
Héctor Peinado, Haiying Zhang, Irina R Matei, Bruno Costa-Silva, Ayuko Hoshino, Goncalo Rodrigues, Bethan Psaila, Rosandra N Kaplan, Jacqueline F Bromberg, Yibin Kang, Mina J Bissell, Thomas R Cox, Amato J Giaccia, Janine T Erler, Sachie Hiratsuka, Cyrus M Ghajar, David Lyden
It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche...
March 17, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28302330/precision-surgery-for-colorectal-liver-metastases-opportunities-and-challenges-of-omics-based-decision-making
#10
REVIEW
R P Jones, K W Brudvik, J M Franklin, G J Poston
Precision surgery involves improving patient selection to ensure that surgical intervention that is proven to benefit on a population level is the optimal treatment for each individual patient. For patients with colorectal liver metastases (CRLM), existing prognostic scoring systems rely on well-recognised histopathological features such as size and number of lesions. Advances in preoperative imaging algorithms mean that increasingly low volume disease can be detected, improving assessment of these factors...
March 6, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28280601/minimal-residual-disease-in-melanoma-circulating-melanoma-cells-and-predictive-role-of-mcam-muc18-melcam-cd146
#11
REVIEW
Maria Cristina Rapanotti, Elena Campione, Giulia Spallone, Augusto Orlandi, Sergio Bernardini, Luca Bianchi
Circulating tumour cells (CTCs), identified in numerous cancers including melanoma, are unquestionably considered valuable and useful as diagnostic and prognostic markers. They can be detected at all melanoma stages and may persist long after treatment. A crucial step in metastatic processes is the intravascular invasion of neoplastic cells as circulating melanoma cells (CMCs). Only a small percentage of these released cells are efficient and capable of colonizing with a strong metastatic potential. CMCs' ability to survive in circulation express a variety of genes with continuous changes of signal pathways and proteins to escape immune surveillance...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28274246/decreased-cytokine-production-by-mononuclear-cells-after-severe-gram-negative-infections-early-clinical-signs-and-association-with-final-outcome
#12
Nikolaos Antonakos, Thomas Tsaganos, Volker Oberle, Iraklis Tsangaris, Malvina Lada, Aikaterini Pistiki, Nikolaos Machairas, Maria Souli, Michael Bauer, Evangelos J Giamarellos-Bourboulis
BACKGROUND: Failure of circulating monocytes for adequate cytokine production is a trait of sepsis-induced immunosuppression; however, its duration and association with final outcome are poorly understood. METHODS: We conducted a substudy of a large randomised clinical trial. Peripheral blood mononuclear cells (PBMCs) were isolated within the first 24 h from the onset of systemic inflammatory response syndrome in 95 patients with microbiologically confirmed or clinically suspected gram-negative infections...
March 9, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28267620/cancer-associated-circulating-large-extracellular-vesicles-in-cholangiocarcinoma-and-hepatocellular-carcinoma
#13
Henrike Julich-Haertel, Sabine K Urban, Marcin Krawczyk, Arnulf Willms, Krzysztof Jankowski, Waldemar Patkowski, Beata Kruk, Maciej Krasnodębski, Joanna Ligocka, Robert Schwab, Ines Richardsen, Sebastian Schaaf, Angelina Klein, Sebastian Gehlert, Hanna Sänger, Markus Casper, Jesus M Banales, Detlef Schuppan, Piotr Milkiewicz, Frank Lammert, Marek Krawczyk, Veronika Lukacs-Kornek, Miroslaw Kornek
BACKGROUND AND AIMS: we previously reported that large extracellular vesicles, specifically AnnexinV(+)EpCAM(+)CD147(+) tumour-associated microparticles (taMPs), facilitate the detection of colorectal carcinoma (CRC), non-small cell lung carcinoma (NSCLC) as well as pancreas carcinoma (PaCa). Here we assess the diagnostic value of taMPs for detection and monitoring of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Specifically, we aim to differentiate liver taMPs from other cancer taMPs, such as CRC and NSCLC...
March 3, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28258798/breast-and-renal-cancer-derived-endothelial-colony-forming-cells-share-a-common-gene-signature
#14
Francesco Moccia, Vittoria Fotia, Richard Tancredi, Matteo Giovanni Della Porta, Vittorio Rosti, Elisa Bonetti, Valentina Poletto, Sergio Marchini, Luca Beltrame, Giulia Gallizzi, Gian Antonio Da Prada, Paolo Pedrazzoli, Alberto Riccardi, Camillo Porta, Alberto Zambelli, Maurizio D'Incalci
BACKGROUND: Neovascularisation supports the metastatic switch in many aggressive solid cancers. Tumour neovessels are mostly lined by endothelial cells sprouting from nearby capillaries, but they could also be contributed by circulating endothelial progenitor cells (EPCs). However, scant information is available about tumour-derived EPCs. METHODS: We carried out the first thorough, unbiased comparison of phenotype, function and genotype of normal versus tumour-derived endothelial colony forming cells (ECFCs), a truly endothelial EPC subtype...
February 28, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28252003/integrating-liquid-biopsies-into-the-management-of-cancer
#15
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/28242504/the-proportion-of-circulating-cd45ro-cd8-memory-t-cells-is-correlated-with-clinical-response-in-melanoma-patients-treated-with-ipilimumab
#16
Julia K Tietze, Daniela Angelova, Markus V Heppt, Markus Reinholz, William J Murphy, Michael Spannagl, Thomas Ruzicka, Carola Berking
BACKGROUND: Immune checkpoint blockade (ICB) has been a breakthrough in the treatment of metastatic melanoma. But with only about 20-40% long-term responders and severe side-effects in about 12-17%, finding predictive markers for treatment response is of great interest. METHODS: We prospectively assessed clinical data, haematologic parameters and freshly isolated peripheral blood mononuclear cells of 30 patients treated with ipilimumab (n = 21) and pembrolizumab (n = 9) prior to the first 4 cycles with ICB and before the first tumour assessment...
February 24, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28239467/ccr7-selected-gene-modified-t-cells-maintain-a-central-memory-phenotype-and-display-enhanced-persistence-in-peripheral-blood-in-vivo
#17
Gray Kueberuwa, Hannah Gornall, Erik Marcelo Alcantar-Orozco, Deborah Bouvier, Zainul Abedin Kapacee, Robert Edward Hawkins, David Edward Gilham
BACKGROUND: Adoptive T cell immunotherapy (ATCT) for cancer entails infusing patients with T cells that recognise and destroy tumour cells. Efficient engraftment of T cells and persistence in the circulation correlate with favourable clinical outcomes. T cells of early differentiation possess an increased capacity for proliferation and therefore persistence, using these cells for ATCT could therefore lead to improved clinical outcomes. METHOD: We describe a method to enrich T cells of early differentiation status using paramagnetic beads and antibodies targeting cells expressing C-C motif chemokine receptor 7 (CCR7)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28238213/extracellular-renalase-protects-cells-and-organs-by-outside-in-signalling
#18
REVIEW
Yang Wang, Robert Safirstein, Heino Velazquez, Xiao-Jia Guo, Lindsay Hollander, John Chang, Tian-Min Chen, Jian-Jun Mu, Gary V Desir
Renalase was discovered as a protein synthesized by the kidney and secreted in blood where it circulates at a concentration of approximately 3-5 μg/ml. Initial reports suggested that it functioned as an NAD(P)H oxidase and could oxidize catecholamines. Administration of renalase lowers blood pressure and heart rate and also protects cells and organs against ischaemic and toxic injury. Although renalase's protective effect was initially ascribed to its oxidase properties, a paradigm shift in our understanding of the cellular actions of renalase is underway...
February 26, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28230065/in-vivo-evaluation-of-a-novel-format-of-a-bivalent-her3-targeting-and-albumin-binding-therapeutic-affibody-construct
#19
Tarek Z Bass, Maria Rosestedt, Bogdan Mitran, Fredrik Y Frejd, John Löfblom, Vladimir Tolmachev, Stefan Ståhl, Anna Orlova
Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28212385/the-effect-of-tumour-size-on-drug-transport-and-uptake-in-3-d-tumour-models-reconstructed-from-magnetic-resonance-images
#20
Wenbo Zhan, Wladyslaw Gedroyc, Xiao Yun Xu
Drug transport and its uptake by tumour cells are strongly dependent on tumour properties, which vary in different types of solid tumours. By simulating the key physical and biochemical processes, a numerical study has been carried out to investigate the transport of anti-cancer drugs in 3-D tumour models of different sizes. The therapeutic efficacy for each tumour is evaluated by using a pharmacodynamics model based on the predicted intracellular drug concentration. Simulation results demonstrate that interstitial fluid pressure and interstitial fluid loss vary non-linearly with tumour size...
2017: PloS One
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