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Circulating tumor cell

David M Barris, Shoshana B Weiner, Robert A Dubin, Michael Fremed, Xusheng Zhang, Sajida Piperdi, Wendong Zhang, Shahina Maqbool, Jonathan Gill, Michael Roth, Bang Hoang, David Geller, Richard Gorlick, Daniel A Weiser
Identification and quantification of somatic alterations in plasma-derived, circulating tumor DNA (ctDNA) is gaining traction as a non-invasive and cost effective method of disease monitoring in cancer patients, particularly to evaluate response to treatment and monitor for disease recurrence. To our knowledge, genetic analysis of ctDNA in osteosarcoma has not yet been studied. To determine whether somatic alterations can be detected in ctDNA and perhaps applied to patient management in this disease, we collected germline, tumor, and serial plasma samples from pediatric, adolescent, and young adult patients with osteosarcoma and used targeted Next Generation Sequencing (NGS) to identify somatic single nucleotide variants (SNV), insertions and deletions (INDELS), and structural variants (SV) in 7 genes commonly mutated in osteosarcoma...
February 27, 2018: Oncotarget
Fang Hu, Xiaowei Mao, Yujun Zhang, Xiaoxuan Zheng, Ping Gu, Huimin Wang, Xueyan Zhang
Purpose: To evaluate the clinical value of circulating tumor cells as a surrogate to detect epidermal growth factor receptor mutation in advanced non-small-cell lung cancer (NSCLC) patients. Methods: We searched the electronic databases, and all articles meeting predetermined selection criteria were included in this study. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated. The evaluation indexes of the diagnostic performance were the summary receiver operating characteristic curve and area under the summary receiver operating characteristic curve...
2018: OncoTargets and Therapy
Katharina E Effenberger, Cornelia Schroeder, Annkathrin Hanssen, Stefan Wolter, Christine Eulenburg, Michael Tachezy, Florian Gebauer, Jakob R Izbicki, Klaus Pantel, Maximilian Bockhorn
PURPOSE: Pancreatic cancer is one of the most devastating diseases with a 5-year survival rate of 3-5%. Here we investigated if circulating tumor cells (CTCs) may predict metastatic spread and survival in pancreatic cancer patients. EXPERIMENTAL DESIGN: In a prospective study we enrolled 69 pancreatic cancer patients. In peripheral blood CTCs were identified by MACS enrichment (anti-cytokeratin/anti-EpCam) and subsequent automated analysis after combined anti-cytokeratin/anti-CD45/DAPI staining...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Benedito A Carneiro, Sahithi Pamarthy, Ami N Shah, Vinay Sagar, Kenji Unno, HuiYing Han, Ximing J Yang, Rubens B Costa, Rebecca J Nagy, Richard B Lanman, Timothy M Kuzel, Jeffrey S Ross, Laurie Gay, Julia A Elvin, Siraj M Ali, Massimo Cristofanilli, Young Kwang Chae, Francis J Giles, Sarki A Abdulkadir
PURPOSE: Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise de novo or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase (ALK) gene are involved in neuroblastoma, lung cancer, and other malignancies but its role in SCCP has not been documented. We describe a patient with refractory de novo SCCP with ALK F1174C activating mutation who obtained clinical benefit from treatment with ALK inhibitor. EXPERIMENTAL DESIGN: Next-generation sequencing (NGS) was used to analyze primary and circulating tumor DNA (ctDNA)...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sandhya Sharma, Rachel Zhuang, Marisa Long, Mirjana Pavlovic, Yunqing Kang, Azhar Ilyas, Waseem Asghar
Circulating tumor cells (CTCs) are a major contributor of cancer metastases and hold a promising prognostic significance in cancer detection. Performing functional and molecular characterization of CTCs provides in-depth knowledge about this lethal disease. Researchers are making efforts to design devices and develop assays for enumeration of CTCs with a high capture and detection efficiency from whole blood of cancer patients. The existing and on-going research on CTC isolation methods has revealed cell characteristics which are helpful in cancer monitoring and designing of targeted cancer treatments...
March 17, 2018: Biotechnology Advances
Jamie Mong, Min-Han Tan
Enumeration of circulating tumor cells (CTCs) in the bloodstream can predict prognosis and survival in cancer patients. However, CTC rarity and heterogeneity pose challenges in using them as biomarkers. Recent publications have reported new classes of circulating, non-cancerous tumor-derived cells present in cancer patients but not in healthy controls; these include cancer-associated macrophages, tumor-endothelial clusters (TECs), and cancer-associated fibroblasts (CAFs). Well-established marker-dependent CTC enrichment technologies will miss this group of circulating cells...
March 17, 2018: Trends in Biotechnology
Anna Babayan, Klaus Pantel
Progress in sensitive analytical approaches has opened new avenues for the detection of cells or products such as circulating cell-free DNA released by tumors. These 'liquid biopsies' are being explored in clinical trials for early cancer detection, prediction of recurrent disease, and assessment of therapeutic resistance mechanisms.
March 20, 2018: Genome Medicine
Mary Jo Fidler, Cristina L Fhied, Joanna Roder, Sanjib Basu, Selina Sayidine, Ibtihaj Fughhi, Mark Pool, Marta Batus, Philip Bonomi, Jeffrey A Borgia
BACKGROUND: The VeriStrat test is a serum proteomic signature originally discovered in non-responders to second line gefitinib treatment and subsequently used to predict differential benefit from erlotinib versus chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC). Multiple studies highlight the clinical utility of the VeriStrat test, however, the mechanistic connection between VeriStrat-poor classification and poor prognosis in untreated and previously treated patients is still an active area of research...
March 20, 2018: BMC Cancer
Celina Yang, Kyle Bromma, Devika Chithrani
Optimizing the interface between nanoparticles (NPs) and the biological environment at various levels should be considered for improving delivery of NPs to the target tumor area. For NPs to be successfully delivered to cancer cells, NPs needs to be functionalized for circulation through the blood vessels. In this study, accumulation of Polyethylene Glycol (PEG) functionalized gold nanoparticles (GNPs) was first tested using in vitro monolayer cells and multilayer cell models prior to in vivo models. A diameter of 10 nm sized GNP was selected for this study for sufficient penetration through tumor tissue...
March 20, 2018: Cancers
Yaw Opoku-Damoah, Assogba G Assanhou, Mopa A Sooro, Cynthia A Baduweh, Chunmeng Sun, Yang Ding
The circulation of tumor cells in peripheral blood is mostly recognized as a prerequisite for cancer progression or systemic invasion, and it correlates with the pivotal hallmark of malignancies known as metastasis. Multiple detection schemes for CTCs have emerged as the most discerning criteria for monitoring the outcome of anticancer therapy. Therefore, there has been a tremendous increase in the use of robust nanostructured platforms for observation of these mobile tumor cells through various simultaneous diagnosis and treatment regimens developed from conventional techniques...
March 20, 2018: ACS Applied Materials & Interfaces
Francois Pognan, J Andreas Mahl, Maria Papoutsi, David Ledieu, Marc Raccuglia, Diethilde Theil, Sarah B Voytek, Patrick J Devine, Katie Kubek-Luck, Natalie Claudio, Andre Cordier, Annabelle Heier, Carine Kolly, Andreas Hartmann, Salah-Dine Chibout, Page Bouchard, Christian Trendelenburg
A high incidence of hemangiosarcoma (HSA) was observed in mice treated for 2 years with siponimod, a sphingosine-1-phosphate receptor 1 (S1P1) functional antagonist, while no such tumors were observed in rats under the same treatment conditions. In 3-month rat (90 mg/kg/day) and 9-month mouse (25 and 75 mg/kg/day) in vivo mechanistic studies, vascular endothelial cell (VEC) activation was observed in both species, but VEC proliferation and persistent increases in circulating placental growth factor 2 (PLGF2) were only seen in the mouse...
March 19, 2018: Archives of Toxicology
Lingling Shan, Xin Zhuo, Fuwu Zhang, Yunlu Dai, Guizhi Zhu, Bryant C Yung, Wenpei Fan, Kefeng Zhai, Orit Jacobson, Dale O Kiesewetter, Ying Ma, Guizhen Gao, Xiaoyuan Chen
Folate receptor (FR) has proven to be a valuable target for chemotherapy using folic acid (FA) conjugates. However, FA-conjugated chemotherapeutics still have low therapeutic efficacy accompanied with side effects, resulting from complications such as short circulation half-life, limited tumor delivery, as well as high kidney accumulation. Herein, we present a novel FA-conjugated paclitaxel (PTX) prodrug which was additionally conjugated with an Evans blue (EB) derivative for albumin binding. The resulting bifunctional prodrug prolonged blood circulation, enhanced tumor accumulation, and consequently improved tumor therapeutic efficacy...
2018: Theranostics
Qinqin Huang, Fu-Bing Wang, Chun-Hui Yuan, Zhaobo He, Lang Rao, Bo Cai, Bolei Chen, Susu Jiang, Zhiqiang Li, Jincao Chen, Wei Liu, Feng Guo, Zheng Ao, Shi Chen, Xing-Zhong Zhao
Background: Circulating tumor cells (CTCs) are a burgeoning topic in cancer biomarker discovery research with minimal invasive blood draws. CTCs can be used as potential biomarkers for disease prognosis, early cancer diagnosis and pharmacodynamics. However, the extremely low abundance of CTCs limits their clinical utility because of technical challenges such as the isolation and subsequent detailed molecular and functional characterization of rare CTCs from patient blood samples. Methods: In this study, we present a novel density gradient centrifugation method employing biodegradable gelatin nanoparticles coated on silicon beads for the isolation, release, and downstream analysis of CTCs from colorectal and breast cancer patients...
2018: Theranostics
Ruilian Xu, Guolin Zhong, Tanxiao Huang, Wan He, Cheng Kong, Xiaoni Zhang, Ying Wang, Ming Liu, Mingyan Xu, Shifu Chen
Lung cancer is the most commonly occurring type of cancer worldwide and also has the highest mortality rate. Although targeted therapy of non-small cell lung carcinoma (NSCLC) has become common, the majority of patients receiving first-line epithelial growth factor receptor (EGFR)-TKI treatment develop drug resistance. The EGFR T790M (NM_005228.4(EGFR):c.2369C>T (p.Thr790Met)) mutation accounts for half of all reported resistance cases; however, the molecular mechanism resulting in the drug resistance remains to be characterized...
March 2018: Oncology Letters
Nuno Couto, Sergio Caja Galán, Joana Maia, Maria Carolina Strano Moraes, Bruno Costa-Silva
Oncologic diseases do not behave as isolated entities. Instead, they are based on complex systemic networks involving cell-cell communication between cancerous and healthy cells of the host, which may either facilitate or prevent cancer progression. In addition to cell-cell contacts, cells communicate through secreted factors in a process modulated by ligand concentration, receptor availability and synergy amongst several signaling circuits. Of these secreted factors, exosomes, 30 to 150 nm membrane vesicles of endocytic origin released by virtually all cells, have emerged as important cell-cell communication players both in physiological and pathological scenarios by being carriers of all the main biomolecules, including lipids, proteins, DNAs, messenger RNAs and microRNA, and performing intercellular transfer of components, locally and systemically...
March 16, 2018: Biochimie
Tanja Jene, Nils C Gassen, Verena Opitz, Kristina Endres, Marianne B Müller, Michael A van der Kooij
Understanding the neurobiological mechanisms underlying the response to an acute stressor may provide novel insights into successful stress-coping strategies. Acute behavioral stress-effects may be restricted to a specific time window early after stress-induction. However, existing behavioral test batteries typically span multiple days or even weeks, limiting the feasibility for a broad behavioral analysis following acute stress. Here, we designed a novel comprehensive behavioral test battery in male mice that assesses multiple behavioral dimensions within a sufficiently brief time window to capture acute stress-effects and its temporal profile...
March 8, 2018: Psychoneuroendocrinology
Jill Koshiol, Yu-Tang Gao, Amanda Corbel, Troy J Kemp, Ming-Chang Shen, Allan Hildesheim, Ann W Hsing, Asif Rashid, Bingsheng Wang, Ruth M Pfeiffer, Ligia A Pinto
BACKGROUND: Inflammatory proteins could help identify individuals most likely to have gallbladder cancer (GBC) among those waiting for cholecystectomy. METHODS: We analyzed 49 circulating inflammation-related proteins in 144 patients with GBC and 150 patients with gallstones. We calculated age- and sex-adjusted odds ratios (ORs) and 95% CIs for protein quantiles and GBC versus gallstones. Using proteins associated with early GBC (stage 1-2) that were selected in stepwise logistic regression, we created an inflammation score and explored the potential utility for risk stratification...
March 16, 2018: Cancer Epidemiology
M E Rodríguez-Ruiz, J L Perez-Gracia, I Rodríguez, C Alfaro, C Oñate, G Pérez, I Gil-Bazo, A Benito, S Inogés, A López-Diaz de Cerio, M Ponz-Sarvise, L Resano, P Berraondo, B Barbés, S Martin-Algarra, A Gúrpide, M F Sanmamed, C de Andrea, A M Salazar, I Melero
BACKGROUND: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. PATIENTS AND METHODS: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24h with poly-ICLC (Hiltonol), TNF-α and IFN-α...
March 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Theodore Gourdin
PURPOSE OF REVIEW: Summarizes recent advances in the treatment of metastatic castration-sensitive and castration-resistant prostate cancer. RECENT FINDINGS: New randomized data suggest a survival advantage to early abiraterone in castration-sensitive metastatic prostate cancer. Prospective and retrospective studies are examining sequencing of existing cytotoxic and androgen-receptor-targeted therapies in both castration-sensitive and castration-resistant disease...
March 16, 2018: Current Opinion in Oncology
Kavi Devraj, Sylvaine Guérit, Jakranka Macas, Yvonne Reiss
Blood-brain barrier (BBB) is a specialized barrier that protects the brain microenvironment from toxins and pathogens in the circulation and maintains brain homeostasis. The principal sites of the barrier are endothelial cells of the brain capillaries whose barrier function results from tight intercellular junctions and efflux transporters expressed on the plasma membrane. This function is regulated by pericytes and astrocytes that together form the neurovascular unit (NVU). Several neurological diseases such as stroke, Alzheimer's disease (AD), brain tumors are associated with an impaired BBB function...
February 26, 2018: Journal of Visualized Experiments: JoVE
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