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Circulating tumors cells

Sara Westrøm, Tina B Bønsdorff, Nasir Abbas, Øyvind S Bruland, Thora J Jonasdottir, Gunhild M Mælandsmo, Roy H Larsen
BACKGROUND: Osteosarcoma is a rare form of cancer but with a substantial need for new active drugs. There is a particular need for targeted therapies to combat metastatic disease. One possible approach is to use an antibody drug conjugate or an antibody radionuclide conjugate to target the osteosarcoma metastases and circulating tumor cells. Herein we have evaluated a radiolabeled monoclonal antibody targeting CD146 both in vitro and in vivo. METHODS AND RESULTS: A murine monoclonal anti-CD146 IgG1 isotype antibody, named OI-3, was developed along with recombinant chimeric versions with human IgG1 or human IgG3 Fc sequences...
2016: PloS One
Shaghayegh Fathi, Adegboyega K Oyelere
Liposomes are biodegradable and biocompatible self-forming spherical lipid bilayer vesicles. They can encapsulate and deliver one or more hydrophobic and hydrophilic therapeutic agents with poor therapeutic indices to tumor sites. Properties such as lipid bilayer fluidity, charge, size and surface hydration can be modified to extend liposome circulation time in the bloodstream and enhance efficacy. The focus of this review is on ligand-conjugated liposomes and their potential application in tumor-targeted delivery...
October 24, 2016: Future Medicinal Chemistry
Chun Wang, Zhaomei Mu, Inna Chervoneva, Laura Austin, Zhong Ye, Giovanna Rossi, Juan P Palazzo, Carl Sun, Maysa Abu-Khalaf, Ronald E Myers, Zhu Zhu, Yanna Ba, Bingshan Li, Lifang Hou, Massimo Cristofanilli, Hushan Yang
PURPOSE: Circulating tumor cell (CTC) is a well-established prognosis predictor for metastatic breast cancer (MBC), and CTC-cluster exhibits significantly higher metastasis-promoting capability than individual CTCs. Because measurement of CTCs and CTC-clusters at a single time point may underestimate their prognostic values, we aimed to analyze longitudinally collected CTCs and CTC-clusters in MBC prognostication. METHODS: CTCs and CTC-clusters were enumerated in 370 longitudinally collected blood samples from 128 MBC patients...
October 22, 2016: Breast Cancer Research and Treatment
David T Miyamoto, Richard J Lee
The recent expansion of therapeutic options for the treatment of metastatic prostate cancer highlights the need for precision medicine approaches to enable the rational selection of appropriate therapies for individual patients. In this context, circulating biomarkers in the peripheral blood are attractive as readily accessible tools for predicting and monitoring therapeutic response. In the case of circulating tumor cells and circulating tumor DNA, they may also serve as a noninvasive means of assessing molecular aberrations in tumors at multiple time points before and during therapy...
October 19, 2016: Urologic Oncology
Erika Heninger, Timothy E G Krueger, Stephanie M Thiede, Jamie M Sperger, Brianna L Byers, Madison R Kircher, David Kosoff, Bing Yang, David F Jarrard, Douglas G McNeel, Joshua M Lang
Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2'-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589...
October 17, 2016: Oncotarget
Cuijuan Yu, Hai Wang, Aaron Muscarella, Amit Goldstein, Huan-Chang Zeng, Yangjin Bae, Brendan H I Lee, Xiang H-F Zhang
Intra-iliac artery (IIA) injection is an efficient approach to introduce metastatic lesions of various cancer cells in animals. Compared to the widely used intra-cardiac and intra-tibial injections, IIA injection brings several advantages. First, it can deliver a large quantity of cancer cells specifically to hind limb bones, thereby providing spatiotemporally synchronized early-stage colonization events and allowing robust quantification and swift detection of disseminated tumor cells. Second, it injects cancer cells into the circulation without damaging the local tissues, thereby avoiding inflammatory and wound-healing processes that confound the bone colonization process...
September 26, 2016: Journal of Visualized Experiments: JoVE
Bernice M Benoit, Neha Jariwala, Geraldine O'Connor, Landon K Oetjen, Timothy M Whelan, Adrienne Werth, Andrea B Troxel, Hélène Sicard, Lisa Zhu, Christopher Miller, Junko Takeshita, Daniel W McVicar, Brian S Kim, Alain H Rook, Maria Wysocka
Sézary syndrome (SS), a leukemic variant of cutaneous T-cell lymphoma (CTCL), is associated with a significantly shorter life expectancy compared to skin-restricted mycosis fungoides. Early diagnosis of SS is, therefore, key to achieving enhanced therapeutic responses. However, the lack of a biomarker(s) highly specific for malignant CD4(+) T cells in SS patients has been a serious obstacle in making an early diagnosis. We recently demonstrated the high expression of CD164 on CD4(+) T cells from Sézary syndrome patients with a wide range of circulating tumor burdens...
October 20, 2016: Archives of Dermatological Research
Quan Zhou, Zhao Li, Juan Zhou, Bishnu P Joshi, Gaoming Li, Xiyu Duan, Rork Kuick, Scott R Owens, Thomas D Wang
EGFR is a promising cell surface target for in vivo imaging that is highly overexpressed in hepatocellular carcinoma (HCC), a common cancer worldwide. Peptides penetrate easily into tumors for deep imaging, and clear rapidly from the circulation to minimize background. We aim to demonstrate use of an EGFR specific peptide to detect HCC xenograft tumors in mice with photoacoustic imaging. Nude mice implanted with human HCC cells that overexpress EGFR were injected intravenously with Cy5.5-labeled EGFR and scrambled control peptides respectively...
June 2016: Photoacoustics
Lori E Lowes, David Goodale, Ying Xia, Carl Postenka, Matthew M Piaseczny, Freeman Paczkowski, Alison L Allan
Metastasis is the cause of most prostate cancer (PCa) deaths and has been associated with circulating tumor cells (CTCs). The presence of ≥5 CTCs/7.5mL of blood is a poor prognosis indicator in metastatic PCa when assessed by the CellSearch® system, the "gold standard" clinical platform. However, ~35% of metastatic PCa patients assessed by CellSearch® have undetectable CTCs. We hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and subsequent loss of necessary CTC detection markers, with important implications for PCa metastasis...
October 15, 2016: Oncotarget
Chao Fang, Chuanwen Fan, Cun Wang, Qiaorong Huang, Wentong Meng, Yongyang Yu, Lie Yang, Zhihai Peng, Jiankun Hu, Yuan Li, Xianming Mo, Zongguang Zhou
INTRODUCTION: Liver is the most common site of distant metastasis in colorectal cancer (CRC). Early diagnosis and appropriate treatment selection decides overall prognosis of patients. However, current diagnostic measures were basically imaging but not functional. Circulating tumor cells (CTCs) known as hold the key to understand the biology of metastatic mechanism provide a novel and auxiliary diagnostic strategy for CRC with liver metastasis (CRC-LM). RESULTS: The expression of CD133+ and CD133+CD54+CD44+ cellular subpopulations were higher in the peripheral blood of CRC-LM patients when compared with those without metastasis (P<0...
October 15, 2016: Oncotarget
Nick Beije, Wendy Onstenk, Jaco Kraan, Anieta M Sieuwerts, Paul Hamberg, Luc Y Dirix, Anja Brouwer, Felix E de Jongh, Agnes Jager, Caroline M Seynaeve, Ngoc M Van, John A Foekens, John W M Martens, Stefan Sleijfer
BACKGROUND: Preclinical and clinical studies have reported that human epidermal growth factor receptor 2 (HER2) overexpression yields resistance to endocrine therapies. Here the prevalence and prognostic impact of HER2-positive circulating tumor cells (CTCs) were investigated retrospectively in metastatic breast cancer (MBC) patients with a HER2-negative primary tumor receiving endocrine therapy. Additionally, the prevalence and prognostic significance of HER2-positive CTCs were explored in a chemotherapy cohort, as well as the prognostic impact of the estrogen receptor (ER) CTC status in both cohorts...
October 17, 2016: Neoplasia: An International Journal for Oncology Research
Xing-Hui Gao, Lu Tian, Jiong Wu, Xiao-Lu Ma, Chun-Yan Zhang, Yan Zhou, Yun-Fan Sun, Bo Hu, Shuang-Jian Qiu, Jian Zhou, Jia Fan, Wei Guo, Xin-Rong Yang
BACKGROUND AND AIM: Myeloid-derived suppressor cells (MDSCs) play an important role in tumor progression. The aim of the present study was to investigate the prognostic value of MDSCs for early recurrence of hepatocellular carcinoma (HCC) patients undergoing curative resection. METHODS: MDSCs were measured by flow cytometry. The correlation between MDSCs and tumor recurrence were analyzed using a cohort of 183 patients who underwent curative resection between February 2014 and July 2015...
October 20, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
O Lidický, M Šírová, T Etrych
In this paper, we describe the synthesis, physicochemical characterization, drug release kinetics and preliminary biological evaluation of several N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer-retinoid conjugates designed for solid tumor immunotherapy. The conjugates are supposed to inhibit the immunosuppressive activity of myeloid-derived suppressor cells (MDSC) accumulated in the solid tumor microenvironment. All-trans retinoic acid (ATRA) was derivatized to hydrazide (AtrHy) and then attached to the polymer backbone via a spacer that is stable at the normal pH of blood (7...
October 20, 2016: Physiological Research
Caiyan Zhao, Leihou Shao, Jianqing Lu, Chenying Zhao, Yujie Wei, Junxing Liu, Mingjun Li, Yan Wu
Stimuli-responsive nanocarriers with the ability to respond to tumorous heterogeneity have been extensively developed for drug delivery. However, the premature release during blood circulation and insufficient intracellular drug release are still a significant issue. Herein, three disulfide bonds are introduced into the amphiphilic poly(ethylene glycol)-polycaprolactone copolymer blocks to form triple-sensitive cleavable polymeric nanocarrier (tri-PESC NPs) to improve its sensitivity to narrow glutathione (GSH) concentration...
October 20, 2016: Macromolecular Bioscience
Jin Sun Lee, Mark Jesus M Magbanua, John W Park
Recent technological advancements in rare cell analysis have facilitated the detection of circulating tumor cells (CTCs) in the blood of patients diagnosed with breast and other types of cancers. Numerous clinical studies involving the enumeration of CTCs in breast cancer patients have unequivocally demonstrated the prognostic value of these cells. Evidence from recent molecular studies indicates that CTCs may be potential surrogate markers for systemic disease. As such, real-time assessment of therapeutic biomarkers in breast CTCs, such as the estrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2), may have a tremendous impact in guiding-targeted cancer therapy...
October 19, 2016: Breast Cancer Research and Treatment
Eugenio Zoni, Gabri van der Pluijm
The skeleton represents a common site of metastases for osteotropic cancers such as prostate and breast tumors and novel therapeutic targets and new markers for the monitoring of bone lesions are urgently needed. The formation of bone metastases is a complex process that starts at the level of the confined tumor and that is characterized by a dynamic crosstalk between the primary cancer and the future metastatic site, the bone. Factors released by the primary tumor contribute to prepare a fertile "soil", where a "pre-metastatic niche" is established prior to future colonization by cancer cells...
September 2016: Journal of Bone Oncology
Jessalyn M Ubellacker, Sandra S McAllister
Systemic factors including cytokines, cell-free nucleic acids, microvesicles, and platelets are appreciated as important regulators of adenocarcinoma progression. Research findings using pre-clinical mouse models have revealed that many such systemically acting factors are either secreted by or responsive to peripheral tumors and impact bone and bone marrow (collectively referred to as the bone microenvironment) to initiate processes that ultimately govern disease progression, even in the absence of detectable bone metastases...
September 2016: Journal of Bone Oncology
Sarah Hrebien, Ben O'Leary, Matthew Beaney, Gaia Schiavon, Charlotte Fribbens, Amarjit Bhambra, Richard Johnson, Isaac Garcia-Murillas, Nicholas Turner
Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48-72 hours after collection...
2016: PloS One
Vanaja Konduri, Dali Li, Matthew M Halpert, Dan Liang, Zhengdong Liang, Yunyu Chen, William E Fisher, Silke Paust, Jonathan M Levitt, Qizhi Cathy Yao, William K Decker
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, exhibiting a five-year overall survival (OS) of only 7% despite aggressive standard of care. Recent advances in immunotherapy suggest potential application of immune-based treatment approaches to PDAC. To explore this concept further, we treated orthotopically established K-ras(G12D)/p53(-/-) PDAC tumors with gemcitabine and a cell-based vaccine previously shown to generate durable cell-mediated (TH1) immunity...
2016: Oncoimmunology
Ana I Robles, Karina Standahl Olsen, Dana W T Tsui, Vassilis Georgoulias, Jenette Creaney, Katalin Dobra, Mogens Vyberg, Nagahiro Minato, Robert A Anders, Anne-Lise Børresen-Dale, Jianwei Zhou, Pål Sætrom, Boye Schnack Nielsen, Michaela B Kirschner, Hans E Krokan, Vassiliki Papadimitrakopoulou, Ioannis Tsamardinos, Oluf D Røe
The goal of biomarker research is to identify clinically valid markers. Despite decades of research there has been disappointingly few molecules or techniques that are in use today. The "1st International NTNU Symposium on Current and Future Clinical Biomarkers of Cancer: Innovation and Implementation", was held June 16th and 17th 2016, at the Knowledge Center of the St. Olavs Hospital in Trondheim, Norway, under the auspices of the Norwegian University of Science and Technology (NTNU) and the HUNT biobank and research center...
October 19, 2016: Journal of Translational Medicine
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