WorldWideScience

Sample records for targeted cancer imaging

  1. Targeted nanotechnology for cancer imaging.

    Science.gov (United States)

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B; Karathanasis, Efstathios

    2014-09-30

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Targeted Nanotechnology for Cancer Imaging

    Science.gov (United States)

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

    2014-01-01

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

  3. Targeting tumors with nanobodies for cancer imaging and therapy.

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    Oliveira, Sabrina; Heukers, Raimond; Sornkom, Jirawas; Kok, Robbert J; van Bergen En Henegouwen, Paul M P

    2013-12-28

    The use of monoclonal antibodies has revolutionized both cancer therapy and cancer imaging. Antibodies have been used to directly inhibit tumor cell proliferation or to target drugs to tumors. Also in molecular imaging, monoclonal antibodies have found their way to the clinic. Nevertheless, distribution within tumors is hampered by their size, leading to insufficient efficacy of cancer treatment and irregular imaging. An attractive alternative for monoclonal antibodies are nanobodies or VHHs. These are the variable domain of heavy-chain antibodies from animals from the Camelidae family that were first discovered in 1993. Stimulated by the ease of nanobody selection, production, and low immunogenicity potential, a number of nanobodies specific to different disease-related targets have been developed. For cancer therapy, nanobodies have been employed as antagonistic drugs, and more recently, as targeting moieties of effector-domaINS and of drug delivery systems. In parallel, nanobodies have also been employed for molecular imaging with modalities such as nuclear and optical imaging. In this review, we discuss recent developments in the application of nanobodies as targeting moieties in cancer therapy and cancer imaging. With such a wide range of successful applications, nanobodies have become much more than simple antagonists. © 2013.

  4. Targeting SR-BI for cancer diagnostics, imaging and therapy

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    Maneesha Amrita Rajora

    2016-09-01

    Full Text Available Scavenger receptor class B type I (SR-BI plays an important role in trafficking cholesteryl esters between the core of high density lipoprotein and the liver. Interestingly, this integral membrane protein receptor is also implicated in the metabolism of cholesterol by cancer cells, whereby overexpression of SR-BI has been observed in a number of tumours and cancer cell lines, including breast and prostate cancers. Consequently, SR-BI has recently gained attention as a cancer biomarker and exciting target for the direct cytosolic delivery of therapeutic agents. This brief review highlights these key developments in SR-BI-targeted cancer therapies and imaging probes. Special attention is given to the exploration of high density lipoprotein nanomimetic platforms that take advantage of upregulated SR-BI expression to facilitate targeted drug-delivery and cancer diagnostics, and promising future directions in the development of these agents.

  5. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

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    Hao Hong

    2008-01-01

    Full Text Available Carcinoembryonic antigen (CEA, highly expressed in many cancer types, is an important target for cancer diagnosis and therapy. Radionuclide-based imaging techniques (gamma camera, single photon emission computed tomography [SPECT] and positron emission tomography [PET] have been extensively explored for CEA-targeted cancer imaging both preclinically and clinically. Briefly, these studies can be divided into three major categories: antibody-based, antibody fragment-based and pretargeted imaging. Radiolabeled anti-CEA antibodies, reported the earliest among the three categories, typically gave suboptimal tumor contrast due to the prolonged circulation life time of intact antibodies. Subsequently, a number of engineered anti-CEA antibody fragments (e.g. Fab’, scFv, minibody, diabody and scFv-Fc have been labeled with a variety of radioisotopes for CEA imaging, many of which have entered clinical investigation. CEA-Scan (a 99mTc-labeled anti-CEA Fab’ fragment has already been approved by the United States Food and Drug Administration for cancer imaging. Meanwhile, pretargeting strategies have also been developed for CEA imaging which can give much better tumor contrast than the other two methods, if the system is designed properly. In this review article, we will summarize the current state-of-the-art of radionuclide-based cancer imaging targeting CEA. Generally, isotopes with short half-lives (e.g. 18F and 99mTc are more suitable for labeling small engineered antibody fragments while the isotopes with longer half-lives (e.g. 123I and 111In are needed for antibody labeling to match its relatively long circulation half-life. With further improvement in tumor targeting efficacy and radiolabeling strategies, novel CEA-targeted agents may play an important role in cancer patient management, paving the way to “personalized medicine”.

  6. Identifying radiotherapy target volumes in brain cancer by image analysis.

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    Cheng, Kun; Montgomery, Dean; Feng, Yang; Steel, Robin; Liao, Hanqing; McLaren, Duncan B; Erridge, Sara C; McLaughlin, Stephen; Nailon, William H

    2015-10-01

    To establish the optimal radiotherapy fields for treating brain cancer patients, the tumour volume is often outlined on magnetic resonance (MR) images, where the tumour is clearly visible, and mapped onto computerised tomography images used for radiotherapy planning. This process requires considerable clinical experience and is time consuming, which will continue to increase as more complex image sequences are used in this process. Here, the potential of image analysis techniques for automatically identifying the radiation target volume on MR images, and thereby assisting clinicians with this difficult task, was investigated. A gradient-based level set approach was applied on the MR images of five patients with grades II, III and IV malignant cerebral glioma. The relationship between the target volumes produced by image analysis and those produced by a radiation oncologist was also investigated. The contours produced by image analysis were compared with the contours produced by an oncologist and used for treatment. In 93% of cases, the Dice similarity coefficient was found to be between 60 and 80%. This feasibility study demonstrates that image analysis has the potential for automatic outlining in the management of brain cancer patients, however, more testing and validation on a much larger patient cohort is required.

  7. Targeting lysyl oxidase for molecular imaging in breast cancer.

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    Wuest, Melinda; Kuchar, Manuela; Sharma, Sai Kiran; Richter, Susan; Hamann, Ingrit; Wang, Monica; Vos, Larissa; Mackey, John R; Wuest, Frank; Löser, Reik

    2015-08-13

    Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1-LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 ((18)F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-NH2, was found to be localized in different cellular compartments under these conditions. After injection of [(18)F]fluorobenzoate-GGGDPKGGGGG-NH2, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the

  8. Integrin αβ3-Targeted Imaging of Lung Cancer

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    Xiaoyuan Chen

    2005-03-01

    Full Text Available A series of radiolabeled cyclic arginine-glycineaspartic acid (RGD peptide ligands for cell adhesion molecule integrin αβ3-targeted tumor angiogenesis targeting are being developed in our laboratory. In this study, this effort continues by applying a positron emitter 64Cu-labeled PEGylated dimeric RGD peptide radiotracer 64Cu-DOTA-PEG-E[c(RGDyK]2 for lung cancer imaging. The PEGylated RGD peptide indicated integrin αβ3 avidity, but the PEGylation reduced the receptor binding affinity of this ligand compared to the unmodified RGD dimer. The radiotracer revealed rapid blood clearance and predominant renal clearance route. The minimum nonspecific activity accumulation in normal lung tissue and heart rendered high-quality orthotopic lung cancer tumor images, enabling clear demarcation of both the primary tumor at the upper lobe of the left lung, as well as metastases in the mediastinum, contralateral lung, diaphragm. As a comparison, fluorodeoxyglucose (FDG scans on the same mice were only able to identify the primary tumor, with the metastatic lesions masked by intense cardiac uptake and high lung background. 64Cu-DOTA-PEGE[c(RGDyK]2 is an excellent positron emission tomography (PET tracer for integrin-positive tumor imaging. Further studies to improve the receptor binding affinity of the tracer and subsequently to increase the magnitude of tumor uptake without comprising the favorable in vivo kinetics are currently in progress.

  9. IGF1 Receptor Targeted Theranostic Nanoparticles for Targeted and Image-Guided Therapy of Pancreatic Cancer.

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    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Wang, Liya; Wang, Y Andrew; Chen, Hongyu; Kooby, David; Yu, Qian; Lipowska, Malgorzata; Staley, Charles A; Mao, Hui; Yang, Lily

    2015-08-25

    Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.

  10. UPAR targeted molecular imaging of cancers with small molecule-based probes.

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    Ding, Feng; Chen, Seng; Zhang, Wanshu; Tu, Yufeng; Sun, Yao

    2017-10-15

    Molecular imaging can allow the non-invasive characterization and measurement of biological and biochemical processes at the molecular and cellular levels in living subjects. The imaging of specific molecular targets that are associated with cancers could allow for the earlier diagnosis and better treatment of diseases. Small molecule-based probes play prominent roles in biomedical research and have high clinical translation ability. Here, with an emphasis on small molecule-based probes, we review some recent developments in biomarkers, imaging techniques and multimodal imaging in molecular imaging and highlight the successful applications for molecular imaging of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Plectin-1 Targeted Dual-modality Nanoparticles for Pancreatic Cancer Imaging

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    Xiao Chen

    2018-04-01

    Full Text Available Background: Biomarker-targeted molecular imaging holds promise for early detection of pancreatic cancer. The aim of this study was to design and evaluate a plectin-1 targeted multi-functional nanoparticle probe for pancreatic cancer imaging. Methods: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-amino(polyethylene glycol (DSPE-PEG-NH2-modified superparamagnetic iron oxide (Fe3O4 nanoparticles (SPION were conjugated with plectin-1 antibody and/or Cy7 to create the multi-functional targeted nanoparticle targeted probe (Plectin-SPION-Cy7 or non-targeted probe (SPION-Cy7. Pancreatic carcinoma cell lines expressing plectin-1 were cultured with the targeted or control probes and then were imaged using confocal laser scanning microscopy and magnetic resonance imaging (MRI. Accumulations of the nanoparticles in pancreatic tumor xenografted mice were determined by MRI and fluorescence imaging. Results: In vitro optical imaging and MRI showed that the targeted nanoparticles were highly accumulated in MIAPaCa2 and XPA-1 carcinoma cells but not in non-carcinoma MIN6 cells, which was further confirmed by Prussian blue staining. In vivo MRI showed a significant T2 signal reduction. Prussian blue staining further confirmed that the plectin-1 targeted nanoparticles were highly accumulated in the tumor mass but not in normal pancreatic tissues, or in the liver and kidney, and few nanoparticles were observed in the tumors of mice injected with SPION-Cy7. Conclusions: Our data demonstrate that plectin-1 targeted fluorescence and MR dual-functional nanoparticle can visualize pancreatic cancer, and it has great potential to be used with various imaging devices for pancreatic cancer detection. Keywords: Pancreatic cancer, Plectin-1, Magnetic resonance imaging, Optical imaging, Nanoparticle

  12. Collagen mimetic peptide engineered M13 bacteriophage for collagen targeting and imaging in cancer.

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    Jin, Hyo-Eon; Farr, Rebecca; Lee, Seung-Wuk

    2014-11-01

    Collagens are over-expressed in various human cancers and subsequently degraded and denatured by proteolytic enzymes, thus making them a target for diagnostics and therapeutics. Genetically engineered bacteriophage (phage) is a promising candidate for the development of imaging or therapeutic materials for cancer collagen targeting due to its promising structural features. We genetically engineered M13 phages with two functional peptides, collagen mimetic peptide and streptavidin binding peptide, on their minor and major coat proteins, respectively. The resulting engineered phage functions as a therapeutic or imaging material to target degraded and denatured collagens in cancerous tissues. We demonstrated that the engineered phages are able to target and label abnormal collagens expressed on A549 human lung adenocarcinoma cells after the conjugation with streptavidin-linked fluorescent agents. Our engineered collagen binding phage could be a useful platform for abnormal collagen imaging and drug delivery in various collagen-related diseases. Published by Elsevier Ltd.

  13. Bone-Targeted Imaging and Radionuclide Therapy in Prostate Cancer.

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    Iagaru, Andrei H; Mittra, Erik; Colletti, Patrick M; Jadvar, Hossein

    2016-10-01

    Although selective metabolic and receptor-based molecular agents will surely be included in the future of prostate cancer diagnosis and therapy, currently available inorganic compounds-such as 18 F-NaF for the diagnosis of bony disease and 223 RaCl 2 for the therapy of bone metastases-were recently shown to be superior to standard 99m Tc-phosphonates for diagnosis and 153 Sm-ethylenediaminetetramethylene phosphonate or 89 SrCl 2 for therapy. The advantages of 18 F-NaF include improved lesion detection and, when used in combination with CT, improved diagnostic confidence and specificity. In addition to being the first approved α-emitter, 223 RaCl 2 is the first radiopharmaceutical to show an increase in overall survival, a decrease in skeletal events, palliation of bone pain, and a low profile of adverse reactions (which are mild and manageable). The management of metastatic bone disease with 223 RaCl 2 is uniquely satisfying, as patients can be monitored directly during their monthly treatment visits. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  14. Ultrasound molecular imaging of ovarian cancer with CA-125 targeted nanobubble contrast agents.

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    Gao, Yong; Hernandez, Christopher; Yuan, Hai-Xia; Lilly, Jacob; Kota, Pavan; Zhou, Haoyan; Wu, Hanping; Exner, Agata A

    2017-10-01

    Ultrasound is frequently utilized in diagnosis of gynecologic malignancies such as ovarian cancer. Because epithelial ovarian cancer (EOC) is often characterized by overexpression of cancer antigen 125 (CA-125), ultrasound contrast agents able to target this molecular signature could be a promising complementary strategy. In this work, we demonstrate application of CA-125-targeted echogenic lipid and surfactant-stabilized nanobubbles imaged with standard clinical contrast harmonic ultrasound for imaging of CA-125 positive OVCAR-3 tumors in mice. Surface functionalization of the nanobubbles with a CA-125 antibody achieved rapid significantly (P CA-125 negative SKOV-3 tumors. Targeted nanobubbles also exhibited increased tumor retention and prolonged echogenicity compared to untargeted nanobubbles. Data suggest that ultrasound molecular imaging using CA-125 antibody-conjugated nanobubbles may contribute to improved diagnosis of EOC. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Development of Lipid-Based Nanoparticles for In Vivo Targeted Delivery of Imaging Agents into Breast Cancer Cells

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    2009-10-01

    targeted therapy. Targeted delivery of a combined imaging and therapy agent to cancer cells is an avenue to develop a new generation of effective and...ligands for targeting HER-2/neu on breast cancer cells . In near future we will test these nanoparticles with SK-BR-3 (HER-2/neu+) and MDA-MD-468 (HER-2/neu-) breast cancer cell lines.

  16. Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study

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    Reuveni T

    2011-11-01

    Full Text Available Tobi Reuveni1, Menachem Motiei1, Zimam Romman2, Aron Popovtzer3, Rachela Popovtzer11Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-ilan University, Ramat Gan, 2GE HealthCare, Tirat Hacarmel, 3Department of Otorhinolaryngology, Head and Neck Surgery and Onology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, IsraelAbstract: In recent years, advances in molecular biology and cancer research have led to the identification of sensitive and specific biomarkers that associate with various types of cancer. However, in vivo cancer detection methods with computed tomography, based on tracing and detection of these molecular cancer markers, are unavailable today. This paper demonstrates in vivo the feasibility of cancer diagnosis based on molecular markers rather than on anatomical structures, using clinical computed tomography. Anti-epidermal growth factor receptor conjugated gold nanoparticles (30 nm were intravenously injected into nude mice implanted with human squamous cell carcinoma head and neck cancer. The results clearly demonstrate that a small tumor, which is currently undetectable through anatomical computed tomography, is enhanced and becomes clearly visible by the molecularly-targeted gold nanoparticles. It is further shown that active tumor targeting is more efficient and specific than passive targeting. This noninvasive and nonionizing molecular cancer imaging tool can facilitate early cancer detection and can provide researchers with a new technique to investigate in vivo the expression and activity of cancer-related biomarkers and molecular processes.Keywords: functional computed tomography, molecular imaging, gold nanoparticles, biologically targeted in vivo imaging, contrast agents

  17. Breast Cancer Detection by B7-H3-Targeted Ultrasound Molecular Imaging.

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    Bachawal, Sunitha V; Jensen, Kristin C; Wilson, Katheryne E; Tian, Lu; Lutz, Amelie M; Willmann, Jürgen K

    2015-06-15

    Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T-cell coregulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor, and malignant breast pathologies for diagnostic purposes. Through an IHC analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3-targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3-targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients. ©2015 American Association for Cancer Research.

  18. Imaging and Therapy of Pancreatic Cancer with Phosphatidylserine-Targeted Nanovesicles

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    Victor M. Blanco

    2015-06-01

    Full Text Available Pancreatic cancer remains one of the most intractable cancers, with a dismal prognosis reflected by a 5-year survival of ~6%. Since early disease symptoms are undefined and specific biomarkers are lacking, about 80% of patients present with advanced, inoperable tumors that represent a daunting challenge. Despite many clinical trials, no single chemotherapy agent has been reliably associated with objective response rates above 10% or median survival longer than 5 to 7 months. Although combination chemotherapy regimens have in recent years provided some improvement, overall survival (8-11 months remains very poor. There is therefore a critical need for novel therapies that can improve outcomes for pancreatic cancer patients. Here, we present a summary of the current therapies used in the management of advanced pancreatic cancer and review novel therapeutic strategies that target tumor biomarkers. We also describe our recent research using phosphatidylserine-targeted saposin C–coupled dioleoylphosphatidylserine nanovesicles for imaging and therapy of pancreatic cancer.

  19. Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study

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    Reuveni, Tobi; Motiei, Menachem; Romman, Zimam; Popovtzer, Aron; Popovtzer, Rachela

    2011-01-01

    In recent years, advances in molecular biology and cancer research have led to the identification of sensitive and specific biomarkers that associate with various types of cancer. However, in vivo cancer detection methods with computed tomography, based on tracing and detection of these molecular cancer markers, are unavailable today. This paper demonstrates in vivo the feasibility of cancer diagnosis based on molecular markers rather than on anatomical structures, using clinical computed tomography. Anti-epidermal growth factor receptor conjugated gold nanoparticles (30 nm) were intravenously injected into nude mice implanted with human squamous cell carcinoma head and neck cancer. The results clearly demonstrate that a small tumor, which is currently undetectable through anatomical computed tomography, is enhanced and becomes clearly visible by the molecularly-targeted gold nanoparticles. It is further shown that active tumor targeting is more efficient and specific than passive targeting. This noninvasive and nonionizing molecular cancer imaging tool can facilitate early cancer detection and can provide researchers with a new technique to investigate in vivo the expression and activity of cancer-related biomarkers and molecular processes. PMID:22131831

  20. Biodegradable nanoparticles for targeted ultrasound imaging of breast cancer cells in vitro

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    Liu Jun [Department of Biomedical Engineering, Ohio State University, 270 Bevis Hall, 1080 Carmack Rd, Columbus, OH 43210 (United States); Li Jie [Department of Biomedical Engineering, Ohio State University, 270 Bevis Hall, 1080 Carmack Rd, Columbus, OH 43210 (United States); Rosol, Thomas J [Department of Veterinary Biosciences, Ohio State University, 1925 Coffey Rd, Columbus, OH 43210 (United States); Pan Xueliang [Department of Statistics, Ohio State University, 1958 Neil Avenue, Columbus, OH 43210 (United States); Voorhees, Jeffrey L [Ohio State Biochemistry Program, Ohio State University, 108 Aronoff Building, 318 West 12 Avenue, Columbus, OH 43210 (United States)

    2007-08-21

    Disease-specific enhanced imaging through a targeted agent promises to improve the specificity of medical ultrasound. Nanoparticles may provide unique advantages for targeted ultrasound imaging due to their novel physical and surface properties. In this study, we examined a nanoparticle agent developed from a biodegradable polymer, polylactic acid (PLA). The nanoparticles (mean diameter = 250 nm) were surface conjugated to an anti-Her2 antibody (i.e., Herceptin) for specific binding to breast cancer cells that overexpress Her2 receptors. We examined the targeting specificity and the resultant ultrasound enhancement in Her2-positive and negative cells. Flow cytometry and confocal imaging were used to assess the nanoparticle-cell binding. Her2-positive cells demonstrated substantial staining after incubation with nanoparticle/antibody conjugates, while minimal staining was found in Her2-negative cells, indicating receptor-specific binding of the conjugated PLA nanoparticles. In high-resolution ultrasound B-mode images, the average gray scale of the Her2-positive cells was consistently and significantly higher after nanoparticle treatment (133 {+-} 4 in treated cells versus 109 {+-} 4 in control, p < 0.001, n = 5), while no difference was detected in the cells that did not overexpress the receptors (117 {+-} 3 in treated cells versus 118 {+-} 5 in control). In conclusion, the feasibility of using targeted nanoparticles to enhance ultrasonic images was demonstrated in vitro. This may be a promising approach to target cancer biomarkers for site-specific ultrasound imaging.

  1. Ultrasonic Nanobubbles Carrying Anti-PSMA Nanobody: Construction and Application in Prostate Cancer-Targeted Imaging.

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    Xiaozhou Fan

    Full Text Available To facilitate prostate cancer imaging using targeted molecules, we constructed ultrasonic nanobubbles coupled with specific anti-PSMA (prostate specific membrane antigen nanobodies, and evaluated their in vitro binding capacity and in vivo imaging efficacy. The "targeted" nanobubbles, which were constructed via a biotin-streptavidin system, had an average diameter of 487.60 ± 33.55 nm and carried the anti-PSMA nanobody as demonstrated by immunofluorescence. Microscopy revealed targeted binding of nanobubbles in vitro to PSMA-positive cells. Additionally, ultrasonography indicators of nanobubble imaging (including arrival time, peak time, peak intensity and enhanced duration were evaluated for the ultrasound imaging in three kinds of animal xenografts (LNCaP, C4-2 and MKN45, and showed that these four indicators of targeted nanobubbles exhibited significant differences from blank nanobubbles. Therefore, this study not only presents a novel approach to target prostate cancer ultrasonography, but also provides the basis and methods for constructing small-sized and high-efficient targeted ultrasound nanobubbles.

  2. A biomimetic theranostic O2-meter for cancer targeted photodynamic therapy and phosphorescence imaging.

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    Li, Shi-Ying; Xie, Bo-Ru; Cheng, Hong; Li, Chu-Xin; Zhang, Ming-Kang; Qiu, Wen-Xiu; Liu, Wen-Long; Wang, Xiao-Shuang; Zhang, Xian-Zheng

    2018-01-01

    In this report, a biomimetic theranostic oxygen (O 2 )-meter (cancer cell membrane@Pt(II) porphyrinic-metal organic framework, designated as mPPt) was constructed for cancer targeted and phosphorescence image-guided photodynamic therapy (PDT). mPPt presents high photosensitizers (PSs) loading and evitable self-quenching behaviors for favorable biological O 2 sensing and PDT. Besides, endowed by the surface functionalization of cancer cell membrane, the homotypic targeting and immune escape abilities of mPPt could dramatically enhance its cancer targeting ability. Importantly, the O 2 -dependent phosphorescence responsibility of mPPt could be employed to pre-evaluate the real time O 2 level in situ and guide the PDT under light irradiation. A significant anticancer effect is observed after intravenous injection of mPPt and subsequent treatment with PDT with no obvious side effects. As a versatile platform for cell imaging, O 2 fluctuation monitoring as well as PDT, this biomimetic O 2 -meter exhibits great potential for biological analysis and personalized cancer theranostics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Cisplatin Prodrug-Conjugated Gold Nanocluster for Fluorescence Imaging and Targeted Therapy of the Breast Cancer.

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    Zhou, Fangyuan; Feng, Bing; Yu, Haijun; Wang, Dangge; Wang, Tingting; Liu, Jianping; Meng, Qingshuo; Wang, Siling; Zhang, Pengcheng; Zhang, Zhiwen; Li, Yaping

    2016-01-01

    Theranostic nanomedicine has emerged as a promising modality for cancer diagnosis and treatment. In this study, we report the fabrication of fluorescence gold nanoclusters (GNC) conjugated with a cisplatin prodrug and folic acid (FA) (FA-GNC-Pt) for fluorescence imaging and targeted chemotherapy of breast cancer. The physio-chemical properties of FA-GNC-Pt nanoparticles are thoroughly characterized by fluorescence/UV-Vis spectroscopic measurement, particle size and zeta-potential examination. We find that FA-modification significantly accelerated the cellular uptake and increased the cytotoxicity of GNC-Pt nanoparticles in murine 4T1 breast cancer cells. Fluorescence imaging in vivo using 4T1 tumor bearing nude mouse model shows that FA-GNC-Pt nanoparticles selectively accumulate in the orthotopic 4T1 tumor and generate strong fluorescence signal due to the tumor targeting effect of FA. Moreover, we demonstrate that FA-GNC-Pt nanoparticles significantly inhibit the growth and lung metastasis of the orthotopically implanted 4T1 breast tumors. All these data imply a good potential of the GNC-based theranostic nanoplatform for fluorescence tumor imaging and cancer therapy.

  4. Biocompatible hyaluronic acid polymer-coated quantum dots for CD44+ cancer cell-targeted imaging

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    Wang, Hening; Sun, Hongfang; Wei, Hui; Xi, Peng; Nie, Shuming; Ren, Qiushi

    2014-10-01

    The cysteamine-modified hyaluronic acid (HA) polymer was employed to coat quantum dots (QDs) through a convenient one-step reverse micelle method, with the final QDs hydrodynamic size of around 22.6 nm. The HA coating renders the QDs with very good stability in PBS for more than 140 days and resistant to large pH range of 2-12. Besides, the HA-coated QDs also show excellent fluorescence stability in BSA-containing cell culture medium. In addition, the cell culture assay indicates no significant cytotoxicity for MD-MB-231 breast cancer cells, and its targeting ability to cancer receptor CD44 has been demonstrated on two breast cancer cell lines. The targeting mechanism was further proved by the HA competition experiment. This work has established a new approach to help solve the stability and toxicity problems of QDs, and moreover render the QDs cancer targeting property. The current results indicate that the HA polymer-coated QDs hold the potential application for both in vitro and in vivo cancer imaging researches.

  5. Targeted Molecular Imaging of Cancer Cells Using MS2-Based 129 Xe NMR

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Keunhong [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Netirojjanakul, Chawita [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Munch, Henrik K. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Sun, Jinny [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Finbloom, Joel A. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Wemmer, David E. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division; Pines, Alexander [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Francis, Matthew B. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division

    2016-07-25

    Targeted, selective, and highly sensitive 129Xe NMR nanoscale biosensors have been synthesized using a spherical MS2 viral capsid, Cryptophane A molecules, and DNA aptamers. The biosensors showed strong binding specificity toward targeted lymphoma cells (Ramos line). Hyperpolarized 129Xe NMR signal contrast and hyper-CEST 129Xe MRI image contrast indicated its promise as highly sensitive hyperpolarized 129Xe NMR nanoscale biosensor for future applications in cancer detection in vivo.

  6. First Experience with Chemokine Receptor CXCR4-Targeted PET Imaging of Patients with Solid Cancers.

    Science.gov (United States)

    Vag, Tibor; Gerngross, Carlos; Herhaus, Peter; Eiber, Matthias; Philipp-Abbrederis, Kathrin; Graner, Frank-Philipp; Ettl, Johannes; Keller, Ulrich; Wester, Hans-Jürgen; Schwaiger, Markus

    2016-05-01

    CXCR4 is a chemokine receptor that is overexpressed in various human cancers and is involved in tumor metastasis. The aim of this proof-of-concept study was to evaluate a novel CXCR4-targeted PET probe in patients with solid cancers with reported in vitro evidence of CXCR4 overexpression and to estimate its potential diagnostic value. Twenty-one patients with histologically proven pancreatic cancer, laryngeal cancer, non-small cell lung cancer, prostate cancer, melanoma, breast cancer, hepatocellular carcinoma, glioblastoma, sarcoma, or cancer of unknown primary underwent PET imaging using the novel CXCR4 nuclear probe (68)Ga-pentixafor. The SUVmax of the liver, spleen, and bone marrow was measured to determine physiologic tracer distribution. For evaluation of tracer accumulation in solid cancers, SUVmax and tumor-to-background (T/B) ratios were determined in a total of 43 malignant lesions, including 8 primary tumors, 3 locally recurrent tumors, and 32 metastases. When available, the SUVmax of malignant lesions was compared with the corresponding SUVmax measured in routine (18)F-FDG PET. Moderate tracer accumulation was detectable in the liver, bone marrow, and spleen, with a mean SUVmax of 3.1, 3.7, and 5.6, respectively. By visual interpretation criteria, 9 of 11 primary and locally recurrent tumors were detectable, exhibiting a mean SUVmax of 4.7 (range, 2.1-10.9) and a mean T/B ratio of 2.9. Twenty of 32 evaluated metastases were visually detectable (mean SUVmax, 4.5 [range, 3.2-13.8]; mean T/B ratio, 2.8). The highest signal was detected in a patient with non-small cell lung cancer (SUVmax, 10.9; T/B ratio, 8.4) and a patient with cancer of unknown primary (SUVmax, 13.8; T/B ratio, 8.1). Compared with (18)F-FDG PET, which was additionally performed in 10 patients, (68)Ga-pentixafor PET had a lower SUVmax in all measured malignant lesions. On the basis of these first observations in a small and heterogeneous patient cohort, the in vitro CXCR4 expression

  7. A novel 111In-labeled anti-PSMA nanobody for targeted SPECT/CT imaging of prostate cancer

    NARCIS (Netherlands)

    Chatalic, K.L.S.; Veldhoven-Zweistra, J.; Bolkestein, M.; Hoeben, S.; Koning, G.A.; Boerman, O.C.; Jong, M. de; Weerden, W.M. van

    2015-01-01

    Prostate-specific Membrane Antigen (PSMA) is overexpressed in prostate cancer (PCa) and a promising target for molecular imaging and therapy. Nanobodies (single domain antibodies, VHH) are the smallest antibody-based fragments possessing ideal molecular imaging properties, such as high target

  8. Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins

    Directory of Open Access Journals (Sweden)

    Martin C. Boonstra

    2016-01-01

    Full Text Available Tumor targeting is a booming business: The global therapeutic monoclonal antibody market accounted for more than $78 billion in 2012 and is expanding exponentially. Tumors can be targeted with an extensive arsenal of monoclonal antibodies, ligand proteins, peptides, RNAs, and small molecules. In addition to therapeutic targeting, some of these compounds can also be applied for tumor visualization before or during surgery, after conjugation with radionuclides and/or near-infrared fluorescent dyes. The majority of these tumor-targeting compounds are directed against cell membrane-bound proteins. Various categories of targetable membrane-bound proteins, such as anchoring proteins, receptors, enzymes, and transporter proteins, exist. The functions and biological characteristics of these proteins determine their location and distribution on the cell membrane, making them more, or less, accessible, and therefore, it is important to understand these features. In this review, we evaluate the characteristics of cancer-associated membrane proteins and discuss their overall usability for cancer targeting, especially focusing on imaging applications.

  9. Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer

    DEFF Research Database (Denmark)

    Sun, Yao; Ma, Xiaowei; Zhang, Zhe

    2016-01-01

    Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high....../g, 2 h) and high tumor/muscle contrast (16.6 ± 1.50 vs 8.42 ± 0.61%ID/g, 2 h). Importantly, biodistribution data indicated a relatively similar accumulation of (68)Ga-NODAGA-SCH1 was observed in the liver (4.21 ± 0.42%ID/g) and kidney (3.41 ± 0.46%ID/g) suggesting that the clearance is through both...... the kidney and the liver. Overall, (68)Ga-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients....

  10. Current perspectives in the use of molecular imaging to target surgical treatments for genitourinary cancers.

    Science.gov (United States)

    Greco, Francesco; Cadeddu, Jeffrey A; Gill, Inderbir S; Kaouk, Jihad H; Remzi, Mesut; Thompson, R Houston; van Leeuwen, Fijs W B; van der Poel, Henk G; Fornara, Paolo; Rassweiler, Jens

    2014-05-01

    Molecular imaging (MI) entails the visualisation, characterisation, and measurement of biologic processes at the molecular and cellular levels in humans and other living systems. Translating this technology to interventions in real-time enables interventional MI/image-guided surgery, for example, by providing better detection of tumours and their dimensions. To summarise and critically analyse the available evidence on image-guided surgery for genitourinary (GU) oncologic diseases. A comprehensive literature review was performed using PubMed and the Thomson Reuters Web of Science. In the free-text protocol, the following terms were applied: molecular imaging, genitourinary oncologic surgery, surgical navigation, image-guided surgery, and augmented reality. Review articles, editorials, commentaries, and letters to the editor were included if deemed to contain relevant information. We selected 79 articles according to the search strategy based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria and the IDEAL method. MI techniques included optical imaging and fluorescent techniques, the augmented reality (AR) navigation system, magnetic resonance imaging spectroscopy, positron emission tomography, and single-photon emission computed tomography. Experimental studies on the AR navigation system were restricted to the detection and therapy of adrenal and renal malignancies and in the relatively infrequent cases of prostate cancer, whereas fluorescence techniques and optical imaging presented a wide application of intraoperative GU oncologic surgery. In most cases, image-guided surgery was shown to improve the surgical resectability of tumours. Based on the evidence to date, image-guided surgery has promise in the near future for multiple GU malignancies. Further optimisation of targeted imaging agents, along with the integration of imaging modalities, is necessary to further enhance intraoperative GU oncologic surgery. Copyright © 2013

  11. Estrogen receptor targeted contrast agents for molecular magnetic resonance imaging of breast cancer hormonal status

    Directory of Open Access Journals (Sweden)

    Adi ePais

    2016-04-01

    Full Text Available The estrogen receptor α (ER is over expressed in most breast cancers and its level serves as a major prognostic factor. It is important to develop quantitative molecular imaging methods that specifically detect ER in vivo and assess its function throughout the entire primary breast cancer, as well as in metastatic breast cancer lesions. This study presents the biochemical and molecular features, as well as the magnetic resonance imaging effects of two novel ER- targeted contrast agents (CAs based on pyridine-tetra-acetate-Gd(III chelate conjugated to 17β-estradiol (EPTA-Gd or to tamoxifen (TPTA-Gd. The experiments were conducted in solution, in human breast cancer cells and in severe combined immunodeficient mice implanted with transfected ER-positive and ER-negative MDA-MB-231 human breast cancer xenografts. Binding studies with ER in solution and in human breast cancer cells indicated affinities in the micromolar range of both CAs. Biochemical and molecular studies in breast cancer cell cultures showed that both CAs exhibit estrogen like agonistic activity, enhancing cell proliferation, as well as up-regulating cMyc oncogene and down-regulating ER expression levels. The MRI longitudinal relaxivity was significantly augmented by EPTA-Gd in ER-positive cells as compared to ER-negative cells. Dynamic contrast enhanced studies with EPTA-Gd in vivo indicated specific augmentation of the MRI water signal in the ER-positive versus ER-negative xenografts, confirming EPTA-Gd specific interaction with ER. In contrast, TPTA-Gd did not show increased enhancement in ER-positive tumors and did not appear to interact in vivo with the tumors’ ER. However, TPTA-Gd was found to interact strongly with muscle tissue, enhancing muscle signal intensity in a mechanism independent of the presence of ER. The specificity of EPTA-Gd interaction with ER in vivo was further verified by acute and chronic competition with tamoxifen. The chronic tamoxifen treatment also

  12. Polymeric micelles for apoptosis-targeted optical imaging of cancer and intraoperative surgical guidance.

    Directory of Open Access Journals (Sweden)

    Hyunah Cho

    Full Text Available In a two-step strategy, an intraperitoneal (IP injection of poly(ethylene glycol-block-poly(ε-caprolactone (PEG-b-PCL micelles containing paclitaxel (PTX, cyclopamine (CYP, and gossypol (GSP at 30, 30, and 30 mg/kg, respectively, debulked tumor tissues by 1.3-fold, based on loss of bioluminescence with <10% body weight change, and induced apoptosis in peritoneal tumors when used as neoadjuvant chemotherapy (NACT in an ES-2-luc-bearing xenograft model for ovarian cancer. In a second step, a single intravenous (i.v. injection of apoptosis-targeting GFNFRLKAGAKIRFGS-PEG-b-PCL micelles containing a near-infrared (NIR fluorescence probe, DiR (1,1'-dioctadecyltetramethyl indotricarbocyanine iodide, resulted in increased peritoneal DiR accumulation in apoptosis-induced ES-2-luc tumor tissues (ex vivo by 1.5-fold compared with DiR molecules delivered by methoxy PEG-b-PCL micelles (non-targeted at 48 h after i.v. injection in a second step. As a result, a tandem of PEG-b-PCL micelles enabled high-resolution detection of ca. 1 mm diameter tumors, resulting in resection of approximately 90% of tumors, and a low peritoneal cancer index (PCI of ca. 7. Thus, a tandem of PEG-b-PCL micelles used for NCAT and NIR fluorescence imaging of therapy-induced apoptosis for intraoperative surgical guidance may be a promising treatment strategy for metastatic ovarian cancer.

  13. Erythrocyte-derived nano-probes functionalized with antibodies for targeted near infrared fluorescence imaging of cancer cells

    Science.gov (United States)

    Mac, Jenny T.; Nuñez, Vicente; Burns, Joshua M.; Guerrero, Yadir A.; Vullev, Valentine I.; Anvari, Bahman

    2016-01-01

    Constructs derived from mammalian cells are emerging as a new generation of nano-scale platforms for clinical imaging applications. Herein, we report successful engineering of hybrid nano-structures composed of erythrocyte-derived membranes doped with FDA-approved near infrared (NIR) chromophore, indocyanine green (ICG), and surface-functionalized with antibodies to achieve molecular targeting. We demonstrate that these constructs can be used for targeted imaging of cancer cells in vitro. These erythrocyte-derived optical nano-probes may provide a potential platform for clinical translation, and enable molecular imaging of cancer biomarkers. PMID:27446657

  14. General Approach to Identifying Potential Targets for Cancer Imaging by Integrated Bioinformatics Analysis of Publicly Available Genomic Profiles

    Directory of Open Access Journals (Sweden)

    Yongliang Yang

    2011-03-01

    Full Text Available Molecular imaging has moved to the forefront of drug development and biomedical research. The identification of appropriate imaging targets has become the touchstone for the accurate diagnosis and prognosis of human cancer. Particularly, cell surface- or membrane-bound proteins are attractive imaging targets for their aberrant expression, easily accessible location, and unique biochemical functions in tumor cells. Previously, we published a literature mining of potential targets for our in-house enzyme-mediated cancer imaging and therapy technology. Here we present a simple and integrated bioinformatics analysis approach that assembles a public cancer microarray database with a pathway knowledge base for ascertaining and prioritizing upregulated genes encoding cell surface- or membrane-bound proteins, which could serve imaging targets. As examples, we obtained lists of potential hits for six common and lethal human tumors in the prostate, breast, lung, colon, ovary, and pancreas. As control tests, a number of well-known cancer imaging targets were detected and confirmed by our study. Further, by consulting gene-disease and protein-disease databases, we suggest a number of significantly upregulated genes as promising imaging targets, including cell surface-associated mucin-1, prostate-specific membrane antigen, hepsin, urokinase plasminogen activator receptor, and folate receptors. By integrating pathway analysis, we are able to organize and map “focused” interaction networks derived from significantly dysregulated entity pairs to reflect important cellular functions in disease processes. We provide herein an example of identifying a tumor cell growth and proliferation subnetwork for prostate cancer. This systematic mining approach can be broadly applied to identify imaging or therapeutic targets for other human diseases.

  15. Targeted imaging of ovarian cancer cells using viral nanoparticles doped with indocyanine green

    Science.gov (United States)

    Guerrero, Yadir; Bahmani, Baharak; Jung, Bonsu; Vullev, Valentine; Kundra, Vikas; Anvari, Bahman

    2013-03-01

    Our group has constructed a new type of viral nanoparticles (VNPs) from genome-depleted plant infecting brome mosaic virus (BMV) that encapsulates the FDA-approved near infrared (NIR) indocyanine green (ICG)[1]. We refer to these VNPs as optical viral ghosts (OVGs) since the constructs lack the genomic content of wild-type BMV. One of our areas of interest is the application of OVGs for real-time intraoperative NIR fluorescence imaging of small peritoneal ovarian tumor nodules. We target human epidermal growth factor receptor-2 (HER-2) expression in ovarian cancer as a biomarker associated with ovarian cancer, since its over-expression is linked to the disease's progression to death. We functionalize the OVGs with anti-HER-2 monoclonal antibodies using reductive amination methods. We used fluorescence imaging to visualize the SKOV-3 cells (high HER-2 expression) after incubation with free ICG, OVGs, and functionalized OVGs. Our results suggest the possibility of using anti-HER2 conjugated OVGs in conjunction with cytoreductive surgery to detect small tumor nodules (<5cm) which currently are not excised during surgery.

  16. Targeted Fluoromagnetic Nanoparticles for Imaging of Breast Cancer MCF-7 Cells

    Directory of Open Access Journals (Sweden)

    Javid Shahbazi

    2013-02-01

    Full Text Available Purpose: To achieve simultaneous imaging and therapy potentials, targeted fluoromagnetic nanoparticles were synthesized and examined in human breast cancer MCF-7 cells. Methods: Fe3O4 nanoparticles (NPs were synthesized through thermal decomposition of Fe(acac3. Then, magnetic nanoparticles (MNPs modified by dopamine-poly ethylene glycol (PEG-NH2; finally, half equivalent fluorescein isothiocyanate (FITC and half equivalent folic acid were conjugated to one equivalent of it. The presence of Fe3O4-DPA-PEG-FA/FITC in the folate receptor (FR positive MCF-7 cells was determined via fluorescent microscopy to monitor the cellular interaction of MNPs. Results: FT-IR spectra of final compound confirmed existence of fluorescein on folic acid grafted MNPs. The Fe3O4-DPA-PEG-FA/FITC NPs, which displayed a size rang about 30-35 nm using scanning electron microscopy (SEM and transmission electron microscopy (TEM, were able to actively recognize the FR-positive MCF-7 cells, but not the FR-negative A549 cells. Conclusion: The uniform nano-sized Fe3O4-DPA-PEG-FA/FITC NPs displayed great potential as theranostics and can be used for targeted imaging of various tumors that overexpress FR.

  17. Intraoperative near-infrared fluorescence imaging targeting folate receptors identifies lung cancer in a large-animal model.

    Science.gov (United States)

    Keating, Jane J; Runge, Jeffrey J; Singhal, Sunil; Nims, Sarah; Venegas, Ollin; Durham, Amy C; Swain, Gary; Nie, Shuming; Low, Philip S; Holt, David E

    2017-05-15

    Complete tumor resection is the most important predictor of patient survival with non-small cell lung cancer. Methods for intraoperative margin assessment after lung cancer excision are lacking. This study evaluated near-infrared (NIR) intraoperative imaging with a folate-targeted molecular contrast agent (OTL0038) for the localization of primary lung adenocarcinomas, lymph node sampling, and margin assessment. Ten dogs with lung cancer underwent either video-assisted thoracoscopic surgery or open thoracotomy and tumor excision after an intravenous injection of OTL0038. Lungs were imaged with an NIR imaging device both in vivo and ex vivo. The wound bed was re-imaged for retained fluorescence suspicious for positive tumor margins. The tumor signal-to-background ratio (SBR) was measured in all cases. Next, 3 human patients were enrolled in a proof-of-principle study. Tumor fluorescence was measured both in situ and ex vivo. All canine tumors fluoresced in situ (mean Fluoptics SBR, 5.2 [range, 2.7-8.1]; mean Karl Storz SBR 1.9 [range, 1.4-2.6]). In addition, the fluorescence was consistent with tumor margins on pathology. Three positive lymph nodes were discovered with NIR imaging. Also, a positive retained tumor margin was discovered upon NIR imaging of the wound bed. Human pulmonary adenocarcinomas were also fluorescent both in situ and ex vivo (mean SBR, > 2.0). NIR imaging can identify lung cancer in a large-animal model. In addition, NIR imaging can discriminate lymph nodes harboring cancer cells and also bring attention to a positive tumor margin. In humans, pulmonary adenocarcinomas fluoresce after the injection of the targeted contrast agent. Cancer 2017;123:1051-60. © 2016 American Cancer Society. © 2016 American Cancer Society.

  18. Spectroscopic Photoacoustic Molecular Imaging of Breast Cancer using a B7-H3-targeted ICG Contrast Agent.

    Science.gov (United States)

    Wilson, Katheryne E; Bachawal, Sunitha V; Abou-Elkacem, Lotfi; Jensen, Kristen; Machtaler, Steven; Tian, Lu; Willmann, Jürgen K

    2017-01-01

    Purpose: Breast cancer imaging methods lack diagnostic accuracy, in particular for patients with dense breast tissue, and improved techniques are critically needed. The purpose of this study was to evaluate antibody-indocyanine green (ICG) conjugates, which undergo dynamic absorption spectrum shifts after cellular endocytosis and degradation, and spectroscopic photoacoustic (sPA) imaging to differentiate normal breast tissue from breast cancer by imaging B7-H3, a novel breast cancer associated molecular target. Methods: Quantitative immunohistochemical staining of endothelial and epithelial B7-H3 expression was assessed in 279 human breast tissue samples, including normal (n=53), benign lesions (11 subtypes, n=129), and breast cancers (4 subtypes, n=97). After absorption spectra of intracellular and degraded B7-H3-ICG and Isotype control-ICG (Iso-ICG) were characterized, sPA imaging in a transgenic murine breast cancer model (FVB/N-Tg(MMTVPyMT)634Mul) was performed and compared to imaging of control conditions [B7-H3-ICG in tumor negative animals (n=60), Iso-ICG (n=30), blocking B7-H3+B7-H3-ICG (n=20), and free ICG (n=20)] and validated with ex vivo histological analysis. Results: Immunostaining showed differential B7-H3 expression on both the endothelium and tumor epithelium in human breast cancer with an area under the ROC curve of 0.93 to differentiate breast cancer vs non-cancer. Combined in vitro/in vivo imaging showed that sPA allowed specific B7-H3-ICG detection down to the 13 nM concentration and differentiation from Iso-ICG. sPA molecular imaging of B7-H3-ICG showed a 3.01-fold (Pbreast cancer. Leveraging antibody-ICG contrast agents and their dynamic optical absorption spectra allows for highly specific sPA imaging of breast cancer.

  19. IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer.

    Science.gov (United States)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui; Yang, Lily

    2016-04-17

    Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

  20. Development of Targeted Nanobubbles for Ultrasound Imaging and Ablation of Metastatic Prostate Cancer Lesions

    Science.gov (United States)

    2014-08-01

    matrix, optically transparent fibrin-based gel phantom embedded with a layer of PC-3 and C4-2B of human prostate cancer , and MDA-MB-231 of breast ... Theranostics , 3(11): 802-815, 2013.  O. Aydin, E. Vlaisavljevich, Y. Y. Durmaz, M. ElSayed1, Z. Xu, “Nanodroplet-Mediated Histotripsy Cancer Cell...Ultrasound Imaging and Ablation of Metastatic Prostate Cancer Lesions PRINCIPAL INVESTIGATOR: Mohamed El-Sayed CONTRACTING ORGANIZATION

  1. Affibody-attached hyperbranched conjugated polyelectrolyte for targeted fluorescence imaging of HER2-positive cancer cell.

    Science.gov (United States)

    Pu, Kan-Yi; Shi, Jianbing; Cai, Liping; Li, Kai; Liu, Bin

    2011-08-08

    A hyperbranched conjugated polyelectrolyte (HCPE) with a core-shell structure is designed and synthesized via alkyne polycyclotrimerization and click chemistry. The HCPE has an emission maximum at 565 nm with a quantum yield of 12% and a large Stokes shift of 143 nm in water. By virtue of its poly(ethylene glycol) shell, this polymer naturally forms spherical nanoparticles that minimize nonspecific interaction with biomolecules in aqueous solution, consequently allowing for efficient bioconjugation with anti-HER2 affibody via carbodiimide-activated coupling reaction. The resulting affibody-attached HCPE can be utilized as a reliable fluorescent probe for targeted cellular imaging of HER2-overexpressed cancer cells such as SKBR-3. Considering its low cytotoxicity and good photostability, the HCPE nanoprobe holds great promise in practical imaging tasks. This study also provides a molecular engineering strategy to overcome the intrinsic limitations of traditional fluorescent polymers (e.g., chromophore-tethered polymers and linear conjugated polyelectrolytes) for bioconjugation and applications.

  2. Human induced pluripotent stem cells labeled with fluorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer

    International Nuclear Information System (INIS)

    Li, Chao; Ruan, Jing; Yang, Meng; Pan, Fei; Gao, Guo; Qu, Su; Shen, You-Lan; Dang, Yong-Jun; Wang, Kan; Jin, Wei-Lin; Cui, Da-Xiang

    2015-01-01

    Human induced pluripotent stem (iPS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human iPS cells labeled with fluorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Human iPS cells were prepared and cultured for 72 h. The culture medium was collected, and then was co-incubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human iPS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer

  3. Plant virus-resembling optical nano-materials conjugated with anti-EGFR for targeted cancer imaging

    Science.gov (United States)

    Gupta, Sharad; Wilder, Hailey; Rao, A. L. N.; Vullev, V. I.; Anvari, Bahman

    2012-03-01

    We recently reported the construction of a new type of optically active nano-particles composed of genome-depleted plant infecting brome mosaic virus (BMV) doped with indocyanine green (ICG), an FDA-approved chromophore . We refer to these constructs as optical viral ghosts (OVGs) since only the capsid protein (CP) subunits of BMV remain to encapsulate ICG. Herein, we covalently conjugated the surface of OVGs with anti-epidermal growth factor receptors (anti-EGFR) to target cancerous human bronchial epithelial cells (C-HBECs) in-vitro. Our preliminary results demonstrate the utility of conjugated OVGs for targeted imaging of cancer cells.

  4. Newer Imaging Modalities to Assist With Target Localization in the Radiation Treatment of Prostate Cancer and Possible Lymph Node Metastases

    International Nuclear Information System (INIS)

    John, Subhash S.; Zietman, Anthony L.; Shipley, William U.; Harisinghani, Mukesh G.

    2008-01-01

    Precise localization of prostate cancer and the drainage lymph nodes is mandatory to define an accurate clinical target volume for conformal radiotherapy. Better target definition and delineation on a daily basis is surely important in quality assurance for fractionated radiation therapy. This article reviews the evidence for major emerging techniques that show promise in better identifying the clinical target volume. Partial prostate boost by brachytherapy, intensity-modulated radiation therapy, or protons has become possible not only with standard imaging techniques but also with the availability of metabolic images obtained by magnetic resonance spectroscopy. Even though fluorine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography has not been found to be useful, novel radiolabeled tracers may eventually prove of value in the diagnosis and treatment planning of prostate cancer. For the metastatic lymph nodes, lymphotropic nanoparticle-enhanced magnetic resonance imaging using ultra-small superparamagnetic iron oxide particles has greater accuracy as compared with conventional techniques and has been instrumental in delineating the lymphatic drainage of the prostate gland. These novel investigational techniques could further help in optimizing conformal radiotherapy for patients with prostate cancer. The concepts of biologic target volume, real target volume, and multidimensional conformal radiotherapy are being explored

  5. Variability of Target and Normal Structure Delineation Using Multimodality Imaging for Radiation Therapy of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dalah, Entesar; Moraru, Ion [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Paulson, Eric [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Erickson, Beth [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Li, X. Allen, E-mail: ali@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

    2014-07-01

    compared with those from CT, except for the kidneys. Conclusions: Differences exists between DCE-, ADC-, and FDG-PET–defined target volumes for RT of pancreatic cancer. Organ at risk volumes based on MRI are generally smaller than those based on CT. Further studies combined with pathologic specimens are required to identify the optimal imaging modality or sequence to define GTV.

  6. Evaluation of EphA2 and EphB4 as Targets for Image-Guided Colorectal Cancer Surgery.

    Science.gov (United States)

    Stammes, Marieke A; Prevoo, Hendrica A J M; Ter Horst, Meyke C; Groot, Stéphanie A; Van de Velde, Cornelis J H; Chan, Alan B; de Geus-Oei, Lioe-Fee; Kuppen, Peter J K; Vahrmeijer, Alexander L; Pasquale, Elena B; Sier, Cornelis F M

    2017-02-03

    Targeted image-guided oncologic surgery (IGOS) relies on the recognition of cell surface-associated proteins, which should be abundantly present on tumor cells but preferably absent on cells in surrounding healthy tissue. The transmembrane receptor tyrosine kinase EphA2, a member of the A class of the Eph receptor family, has been reported to be highly overexpressed in several tumor types including breast, lung, brain, prostate, and colon cancer and is considered amongst the most promising cell membrane-associated tumor antigens by the NIH. Another member of the Eph receptor family belonging to the B class, EphB4, has also been found to be upregulated in multiple cancer types. In this study, EphA2 and EphB4 are evaluated as targets for IGOS of colorectal cancer by immunohistochemistry (IHC) using a tissue microarray (TMA) consisting of 168 pairs of tumor and normal tissue. The IHC sections were scored for staining intensity and percentage of cells stained. The results show a significantly enhanced staining intensity and more widespread distribution in tumor tissue compared with adjacent normal tissue for EphA2 as well as EphB4. Based on its more consistently higher score in colorectal tumor tissue compared to normal tissue, EphB4 appears to be a promising candidate for IGOS of colorectal cancer. In vitro experiments using antibodies on human colon cancer cells confirmed the possibility of EphB4 as target for imaging.

  7. Bio-conjugated luminescent quantum dots of doped ZnS: a cyto-friendly system for targeted cancer imaging

    International Nuclear Information System (INIS)

    Manzoor, Koyakutty; Johny, Seby; Thomas, Deepa; Setua, Sonali; Menon, Deepthy; Nair, Shantikumar

    2009-01-01

    A heavy-metal-free luminescent quantum dot (QD) based on doped zinc sulfide (ZnS), conjugated with a cancer-targeting ligand, folic acid (FA), is presented as a promising bio-friendly system for targeted cancer imaging. Doped QDs were prepared by a simple aqueous method at room temperature. X-ray diffraction and transmission electron microscopy studies showed the formation of monodisperse QDs of average size ∼4 nm with cubic (sphalerite) crystal structure. Doping of the QDs with metals (Al 3+ ), transition metals (Cu + , Mn 2+ ) and halides (F - ) resulted in multi-color emission with dopant-specific color tunability ranging from blue (480 nm) to red (622 nm). Luminescent centers in doped QDs could be excited using bio-friendly visible light >400 nm by directly populating the dopant centers, leading to bright emission. The cytotoxicity of bare and FA conjugated QDs was tested in vitro using normal lung fibroblast cell line (L929), folate-receptor-positive (FR+) nasopharyngeal epidermoid carcinoma cell line (KB), and FR-negative (FR-) lung cancer cell line (A549). Both bare and FA-conjugated ZnS QDs elicited no apparent toxicity even at high concentrations of ∼100 μM and 48 h of incubation. In contrast, CdS QDs prepared under identical conditions showed relatively high toxicity even at low concentrations of ∼0.1 μM and 24 h of incubation. Interaction of FA-QDs with different cell lines showed highly specific attachment of QDs in the FR+ cancer cell line, leaving others unaffected. The bright and stable luminescence of the QDs could be used to image both single cancer cells and colonies of cancer cells without affecting their metabolic activity and morphology. Thus, this study presents, for the first time, the use of non-toxic, Cd-, Te-, Se-, Pb- and Hg-free luminescent QDs for targeted cancer imaging.

  8. Tumor responsive targeted multifunctional nanosystems for cancer imaging, chemo- and siRNA therapy

    Science.gov (United States)

    Savla, Ronak

    Cancer is one of the most insidious diseases. Compromising of over 100 different types and sharing the unifying factors of uncontrolled growth and metastasis, unmet clinical needs in terms of cancer diagnosis and treatment continue to exist. It is widely accepted that most forms of cancer are treatable or even curable if detected before widespread metastasis occurs. Nearly a quarter of deaths in the United States is the result of cancer and it only trails heart disease in terms of annual mortality. Surgery, chemotherapy, and radiation therapy are the primary treatment modalities for cancer. Research in these procedures has resulted in substantial benefits for cancer patients, but there is still room for an improvement. However, a time has been reached at which it appears that the benefits from these modalities have been reached the maximum. Therefore, it is vital to develop new strategies for the diagnosis and treatment of cancer. The field of nanotechnology is concerned with structures in the nanometer size range and holds the potential to drastically impact and improve the lives of patients suffering from cancer. Not only can nanotechnology improve current methods of diagnosis and treatment, it has a possibility of introducing newer and better modalities. The overall purpose of this work is to develop novel nanotechnology-based methodologies for the diagnosis and treatment of various forms of cancers. The first aim of the project is the development of a multifunctional targeted nanosystem for the delivery of siRNA to overcome drug resistance. The second aspect is the synthesis of a quantum dot-based delivery system that releases drug in response to pH changes. The third aim is the development of a targeted, tumor environment responsive magnetic resonance nanoparticle contrast agent coupled with a nanoparticle-based treatment.

  9. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, J. F.; van der Wall, Elsken; Mali, Willem P Th M; Derksen, Patrick W B; van Diest, Paul J; van Bergen En Henegouwen, Paul M P

    PURPOSE: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. PROCEDURES: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  10. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, Jeroen F.; van der Wall, Elsken; Mali, W.P.T.M.; Derksen, Patrick W B; van Diest, Paul J.; van Bergen En Henegouwen, Paul M P

    Purpose: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. Procedures: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  11. Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis

    Science.gov (United States)

    Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

    2016-01-01

    This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine. PMID:28078184

  12. Instrumentation of Molecular Imaging on Site-Specific Targeting Fluorescent Peptide for Early Detection of Breast Cancer

    Science.gov (United States)

    Yu, Ping; Ma, Lixin

    2012-02-01

    In this work we developed two biomedical imaging techniques for early detection of breast cancer. Both image modalities provide molecular imaging capability to probe site-specific targeting dyes. The first technique, heterodyne CCD fluorescence mediated tomography, is a non-invasive biomedical imaging that uses fluorescent photons from the targeted dye on the tumor cells inside human breast tissue. The technique detects a large volume of tissue (20 cm) with a moderate resolution (1 mm) and provides the high sensitivity. The second technique, dual-band spectral-domain optical coherence tomography, is a high-resolution tissue imaging modality. It uses a low coherence interferometer to detect coherent photons hidden in the incoherent background. Due to the coherence detection, a high resolution (20 microns) is possible. We have finished prototype imaging systems for the development of both image modalities and performed imaging experiments on tumor tissues. The spectroscopic/tomographic images show contrasts of dense tumor tissues and tumor necrotic regions. In order to correlate the findings from our results, a diffusion-weighted magnetic resonance imaging (MRI) of the tumors was performed using a small animal 7-Telsa MRI and demonstrated excellent agreement.

  13. Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging.

    Science.gov (United States)

    Mooberry, Linda K; Sabnis, Nirupama A; Panchoo, Marlyn; Nagarajan, Bhavani; Lacko, Andras G

    2016-01-01

    Malignant tumors display remarkable heterogeneity to the extent that even at the same tissue site different types of cells with varying genetic background may be found. In contrast, a relatively consistent marker the scavenger receptor type B1 (SR-B1) has been found to be consistently overexpressed by most tumor cells. Scavenger Receptor Class B Type I (SR-BI) is a high density lipoprotein (HDL) receptor that facilitates the uptake of cholesterol esters from circulating lipoproteins. Additional findings suggest a critical role for SR-BI in cholesterol metabolism, signaling, motility, and proliferation of cancer cells and thus a potential major impact in carcinogenesis and metastasis. Recent findings indicate that the level of SR-BI expression correlate with aggressiveness and poor survival in breast and prostate cancer. Moreover, genomic data show that depending on the type of cancer, high or low SR-BI expression may promote poor survival. This review discusses the importance of SR-BI as a diagnostic as well as prognostic indicator of cancer to help elucidate the contributions of this protein to cancer development, progression, and survival. In addition, the SR-B1 receptor has been shown to serve as a potential gateway for the delivery of therapeutic agents when reconstituted high density lipoprotein nanoparticles are used for their transport to cancer cells and tumors. Opportunities for the development of new technologies, particularly in the areas of cancer therapy and tumor imaging are discussed.

  14. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2007-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  15. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun Ki; Herbst, Roy

    2006-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  16. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2008-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  17. Targeted therapies for cancer

    Science.gov (United States)

    ... Kummar S, Murgo AJ, Tomaszewski JE, Doroshow JH. Therapeutic targeting of cancer cells: era of molecularly targeted agents. ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  18. Magnetic nanoparticles for precision oncology: theranostic magnetic iron oxide nanoparticles for image-guided and targeted cancer therapy.

    Science.gov (United States)

    Zhu, Lei; Zhou, Zhiyang; Mao, Hui; Yang, Lily

    2017-01-01

    Recent advances in the development of magnetic nanoparticles (MNPs) have shown promise in the development of new personalized therapeutic approaches for clinical management of cancer patients. The unique physicochemical properties of MNPs endow them with novel multifunctional capabilities for imaging, drug delivery and therapy, which are referred to as theranostics. To facilitate the translation of those theranostic MNPs into clinical applications, extensive efforts have been made on designing and improving biocompatibility, stability, safety, drug-loading ability, targeted delivery, imaging signal and thermal- or photodynamic response. In this review, we provide an overview of the physicochemical properties, toxicity and theranostic applications of MNPs with a focus on magnetic iron oxide nanoparticles.

  19. Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image-Guided Approaches.

    Science.gov (United States)

    Huang, Jing; Li, Yuancheng; Orza, Anamaria; Lu, Qiong; Guo, Peng; Wang, Liya; Yang, Lily; Mao, Hui

    2016-06-14

    With rapid advances in nanomedicine, magnetic nanoparticles (MNPs) have emerged as a promising theranostic tool in biomedical applications, including diagnostic imaging, drug delivery and novel therapeutics. Significant preclinical and clinical research has explored their functionalization, targeted delivery, controllable drug release and image-guided capabilities. To further develop MNPs for theranostic applications and clinical translation in the future, we attempt to provide an overview of the recent advances in the development and application of MNPs for drug delivery, specifically focusing on the topics concerning the importance of biomarker targeting for personalized therapy and the unique magnetic and contrast-enhancing properties of theranostic MNPs that enable image-guided delivery. The common strategies and considerations to produce theranostic MNPs and incorporate payload drugs into MNP carriers are described. The notable examples are presented to demonstrate the advantages of MNPs in specific targeting and delivering under image guidance. Furthermore, current understanding of delivery mechanisms and challenges to achieve efficient therapeutic efficacy or diagnostic capability using MNP-based nanomedicine are discussed.

  20. Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

    Energy Technology Data Exchange (ETDEWEB)

    Min, Jung Joon; Nguyen, Vu H. [Chonnam National University Medical School, Gwangju (Korea, Republic of); Gambhir, Sanjiv S. [Stanford University, California(United States)

    2010-04-15

    Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonarrival biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.

  1. Theranostic MUC-1 aptamer targeted gold coated superparamagnetic iron oxide nanoparticles for magnetic resonance imaging and photothermal therapy of colon cancer

    DEFF Research Database (Denmark)

    Azhdarzadeh, Morteza; Atyabi, Fatemeh; Saei, Amir Ata

    2016-01-01

    Favorable physiochemical properties and the capability to accommodate targeting moieties make superparamegnetic iron oxide nanoparticles (SPIONs) popular theranostic agents. In this study, we engineered SPIONs for magnetic resonance imaging (MRI) and photothermal therapy of colon cancer cells...

  2. Innovation in cancer imaging.

    Science.gov (United States)

    Debergh, I; Vanhove, C; Ceelen, W

    2012-01-01

    Cancer is rapidly becoming the worldwide leading cause of premature death. Iconographic techniques have traditionally provided information on tumor anatomy. The recent introduction of functional and molecular imaging techniques allows probing tumor physiology and biology in addition to mere anatomical description. In addition to the research implications, these novel imaging techniques offer early response assessment and target visualization which, in the era of personalized medicine, may offer significant advances in cancer therapy. Here, we provide an overview of the most important developments in cancer imaging, with a focus on the clinical applications. Copyright © 2012 S. Karger AG, Basel.

  3. Targeted nanoparticles for image-guided treatment of triple-negative breast cancer: clinical significance and technological advances.

    Science.gov (United States)

    Miller-Kleinhenz, Jasmine M; Bozeman, Erica N; Yang, Lily

    2015-01-01

    Effective treatment of triple-negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and noninvasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise toward the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle-based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor-associated endothelial cells, stromal fibroblasts, and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in-depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as by others, and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. © 2015 Wiley Periodicals, Inc.

  4. Internal target volume for post-hysterectomy vaginal recurrences of cervical cancers during image-guided radiotherapy.

    Science.gov (United States)

    Upasani, Maheshkumar N; Chopra, Supriya; Engineer, Reena; Mahantshetty, Umesh; Medhi, Seema; Mehta, Zubin; Shrivastava, Shyam K

    2015-10-01

    The outcome of post-surgical recurrences of cervical cancer may be improved through radiation dose escalation, which hinges on accurate identification and treatment of the target. The present study quantifies target motion during course of image-guided radiotherapy (IGRT) for vault cancers. All patients underwent planning CT simulation after bladder-filling protocol. A daily pre-treatment megavoltage CT was performed. All translations and rotations were recorded. Post-registration displacement of gross tumour volume (GTV) and centre of mass (COM) of GTV was independently recorded by two observers for fractions one to seven. Day 1 image sets served as reference images against which the displacements of COM were measured. We calculated the displacements of common volume (CV) and encompassing volume (EV) of GTV for both the observers. A total of 90 image data sets of 15 patients were available for evaluation. Individual patient GTV and average GTV by both the observers were comparable. The average shifts for EV were 2.4 mm [standard deviation (SD) ±1.2] in the mediolateral, 4.2 mm (SD ±2.8) in the anteroposterior and 4.0 mm (SD ±2.1) in superoinferior directions. Similarly, the average shifts for CV were 1.9 mm (SD ±0.6) in the mediolateral, 3.7 mm (SD ±2.7) in the anteroposterior and 4.4 mm (SD ±2.7) in superoinferior directions. Using Stroom's/van Herk's formula, the minimum recommended margins would be 4.5/5.2, 8.2/9.4 and 7.3/8.3 mm, respectively, for lateral, anteroposterior and superoinferior directions. Differential directional internal margin is recommended in patients undergoing IGRT for post-surgical recurrence of cervical cancers. Internal organ motion of vault cancers can be accounted for by a directional margin to the gross tumour.

  5. cRGD-conjugated magnetic-fluorescent liposomes for targeted dual-modality imaging of bone metastasis from prostate cancer.

    Science.gov (United States)

    Wang, Fangfang; Chen, Zhongping; Zhu, Li

    2015-01-01

    We reported the development of multifunctional liposomes as a dual-modality probe to facilitate targeted magnetic resonance and fluorescent imaging of bone metastasis from advanced cancer. Multifunctional liposomes consisted of liposomes as a carrier, hydrophobic CdSe QDs in phospholipid bilayer, hydrophilic iron oxide nanoparticles in interior vesicle, lipid-PEG derivative on the surface and cRGDyk peptide conjugated to distal ends of lipid-PEG derivative. Excellent stability, effective detection signal, low toxicity, high resistance to phagocytosis by macrophages and good specificity to tumor of multifunctional liposomes were confirmed by in vitro characterization. The in vivo results demonstrated that multifunctional liposomes accumulated mainly in tumor and liver, indicating that targeted dual-modality imaging was achieved, and the results from two kinds of modalities were consistent and complementary. These findings provide a helpful strategy for detection of bone metastases in a more effective manner for initiation of appropriate therapy.

  6. Estrogen receptor-targeted optical imaging of breast cancer cells with near-infrared fluorescent dye

    Science.gov (United States)

    Jose, Iven; Deodhar, Kodand; Chiplunkar, Shuba V.; Patkar, Meena

    2010-02-01

    Molecular imaging provides the in vivo characterization of cellular molecular events involved in normal and pathologic processes. With the advent of optical molecular imaging, specific molecules, proteins and genes may be tagged with a luminescent reporter and visualized in small animals. This powerful new tool has pushed in vivo optical imaging to the forefront as it allows for direct determination of drug bio-distribution and uptake kinetics as well as an indicator of biochemical activity and drug efficacy. Although optical imaging encompasses diverse techniques and makes use of various wavelengths of light, a great deal of excitement in molecular research lies in the use of tomographic and fluorescence techniques to image living tissues with near-infrared (NIR) light. Nonionizing, noninvasive near-infrared optical imaging has great potential to become promising alternative for breast cancer detection. Fluorescence spectroscopy studies of human tissue suggest that a variety of lesions show distinct fluorescence spectra compared to those of normal tissue. It has also been shown that exogenous dyes exhibit selective uptake in neoplastic lesions and may offer the best contrast for optical imaging. Use of exogenous agents would provide fluorescent markers, which could serve to detect embedded tumors in the breast. In particular, the ability to monitor the fluorescent yield and lifetime may also enable biochemical specificity if the fluorophore is sensitive to a specific metabolite, such as oxygen. As a first step, we have synthesized and characterized one such NIR fluorescent dye conjugate, which could potentially be used to detect estrogen receptors (ER)[2] . The conjugate was synthesized by ester formation between 17-β estradiol and a hydrophilic derivative of indocyanine green (ICG) cyanine dye, bis-1, 1-(4-sulfobutyl) indotricarbocyanine-5- carboxylic acid, sodium salt. The ester formed was found to have an extra binding ability with the receptor cites as

  7. Prostate stem cell antigen-targeted nanoparticles with dual functional properties: in vivo imaging and cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Gao X

    2012-07-01

    Full Text Available Xin Gao,1,* Yun Luo,1,* Yuanyuan Wang,1,* Jun Pang,1 Chengde Liao,2 Hanlun Lu,3 Youqiang Fang11Department of Urology, The Third Affiliated Hospital, 2Department of Radiology, The Second Affiliated Hospital, Sun Yat-Sen University, 3Materials Science Institute of Zhongshan University, Guangzhou, China*These authors contributed equally to this workBackground: We designed dual-functional nanoparticles for in vivo application using a modified electrostatic and covalent layer-by-layer assembly strategy to address the challenge of assessment and treatment of hormone-refractory prostate cancer.Methods: Core-shell nanoparticles were formulated by integrating three distinct functional components, ie, a core constituted by poly(D,L-lactic-co-glycolic acid, docetaxel, and hydrophobic superparamagnetic iron oxide nanocrystals (SPIONs, a multilayer shell formed by poly(allylamine hydrochloride and two different sized poly(ethylene glycol molecules, and a single-chain prostate stem cell antigen antibody conjugated to the nanoparticle surface for targeted delivery.Results: Drug release profiles indicated that the dual-function nanoparticles had a sustained release pattern over 764 hours, and SPIONs could facilitate the controlled release of the drug in vitro. The nanoparticles showed increased antitumor efficiency and enhanced magnetic resonance imaging in vitro through targeted delivery of docetaxel and SPIONs to PC3M cells. Moreover, in nude mice bearing PC3M xenografts, the nanoparticles provided MRI negative contrast enhancement, as well as halting and even reversing tumor growth during the 76-day study duration, and without significant systemic toxicity. The lifespan of the mice treated with these targeted dual-function nanoparticles was significantly increased (Chi-square = 22.514, P < 0.0001.Conclusion: This dual-function nanomedical platform may be a promising candidate for tumor imaging and targeted delivery of chemotherapeutic agents in vivo

  8. Breast cancer cell targeted MR molecular imaging probe: Anti-MUC1 antibody-based magnetic nanoparticles

    Science.gov (United States)

    Moradi Khaniabadi, P.; S. A Majid, A. M.; Asif, M.; Moradi Khaniabadi, B.; Shahbazi-Gahrouei, D.; Jaafar, M. S.

    2017-05-01

    Effective and specific diagnostic imaging techniques are important in early-stage breast cancer treatment. The objective of this study was to develop a specific breast cancer contrast agent for magnetic resonance imaging (MRI). In so doing, superparamagnetic iron oxide nanoparticles (SPIONs) were conjugated to C595 monoclonal antibody using EDC chemistry to produce nanoprobe with high relaxivity and narrow size (87.4±0.7 nm). To test the developed nanoprobe in vitro, assessments including Cell toxicity, targeting efficacy, cellular binding, and MR imaging were carried out. The results indicated that after 6 hrs incubation with MCF-7 cells at 200 to 25 µg Fe/ml doses, 76% to 16% T2 reduction was obtained. The presence of iron localised in MCF-7 cells measured by atomic absorption spectroscopy (AAS) was about 9.95±0.09 ppm iron/cell at higher doses of nanoprobe. Moreover, a linear relationship between iron concentration of nontoxic SPION-C595 and T2 relaxation times was observed. This study also revealed that developed nanoprobe might be used as a specific negative contrast agent for detecting breast cancer.

  9. Multicomponent, peptide-targeted glycol chitosan nanoparticles containing ferrimagnetic iron oxide nanocubes for bladder cancer multimodal imaging

    Directory of Open Access Journals (Sweden)

    Key J

    2016-08-01

    , by using cyanine 5.5 fluorescence molecules. We changed the physicochemical properties of glycol chitosan nanoparticles by conjugating bladder cancer-targeting peptides and loading many ferrimagnetic iron oxide NCs per glycol chitosan nanoparticle to improve MRI contrast. The 22 nm ferrimagnetic NCs were stabilized in physiological conditions by encapsulating them within modified chitosan nanoparticles. The multimodal nanoparticles were compared with in vivo MRI and near infrared fluorescent systems. We demonstrated significant and important changes in the biodistribution and tumor accumulation of nanoparticles with different physicochemical properties. Finally, we demonstrated that multimodal nanoparticles specifically visualize small tumors and show minimal accumulation in other organs. This work reveals the importance of finely modulating physicochemical properties in designing multimodal nanoparticles for bladder cancer imaging.Keywords: MRI, NIRF, multimodal imaging, chitosan, iron oxide, bladder cancer

  10. In vitro and in vivo evaluation of anti-nucleolin-targeted magnetic PLGA nanoparticles loaded with doxorubicin as a theranostic agent for enhanced targeted cancer imaging and therapy.

    Science.gov (United States)

    Mosafer, Jafar; Abnous, Khalil; Tafaghodi, Mohsen; Mokhtarzadeh, Ahad; Ramezani, Mohammad

    2017-04-01

    A superparamagnetic iron oxide nanoparticles (SPIONs)/doxorubicin (Dox) co-loaded poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeted with AS1411 aptamer (Apt) against murine C26 colon carcinoma cells is successfully developed via a modified multiple emulsion solvent evaporation method for theranostic purposes. The mean size of SPIO/Dox-NPs (NPs) was 130nm with a narrow particle size distribution and Dox loading of 3.0%. The SPIO loading of 16.0% and acceptable magnetic properties are obtained and analyzed using thermogravimetric and vibration simple magnetometer analysis, respectively. The best release profile from NPs was observed in PBS at pH 7.4, in which very low burst release was observed. Nucleolin is a targeting ligand to facilitate anti-tumor delivery of AS1411-targeted NPs. The Apt conjugation to NPs (Apt-NPs) enhanced cellular uptake of Dox in C26 cancer cells. Apt-NPs enhance the cytotoxicity effect of Dox followed by a significantly higher tumor inhibition and prolonged animal survival in mice bearing C26 colon carcinoma xenografts. Furthermore, Apt-NPs enhance the contrast of magnetic resonance images in tumor site. Altogether, these Apt-NPs could be considered as a powerful tumor-targeted delivery system for their potential as dual therapeutic and diagnostic applications in cancers. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Cost-Effectiveness of Magnetic Resonance Imaging and Targeted Fusion Biopsy for Early Detection of Prostate Cancer.

    Science.gov (United States)

    Barnett, Christine L; Davenport, Matthew S; Montgomery, Jeffrey S; Wei, John T; Montie, James E; Denton, Brian T

    2018-02-01

    To determine how best to use MRI and targeted MR/ultrasound fusion biopsy for early detection of prostate cancer in men with elevated PSA and whether it can be cost-effective. A Markov model of prostate cancer onset and progression was developed to estimate health and economic consequences of prostate cancer screening with MRI. Men were screened with prostate-specific antigen (PSA) from ages 55 to 69. Men with elevated PSA (>4 ng/mL) received an MRI, followed by targeted fusion or combined (standard + targeted fusion) biopsy on positive MRI, and standard or no biopsy on negative MRI. Prostate imaging reporting and data system (PI-RADS) score on MRI determined biopsy decisions. Deaths averted, quality-adjusted life years (QALYs), cost, and incremental cost-effectiveness ratio (ICER) were estimated for each strategy. With a negative MRI, standard biopsy was more expensive and had lower QALYs than performing no biopsy. The optimal screening strategy (ICER: $23,483/QALY) recommended combined biopsy for men with PI-RADS score ≥3 and no biopsy for men with PI-RADS score <3, and reduced the number of screening biopsies by 15%. Threshold analysis suggests MRI continues to be cost-effective when sensitivity and specificity of MRI and combined biopsy are simultaneously reduced by 19.0. Our analysis suggests MRI followed by targeted MR/ultrasound fusion biopsy can be a cost-effective approach for early detection of prostate cancer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Magnetic resonance molecular imaging of metastatic breast cancer by targeting extradomain-B fibronectin in the tumor microenvironment.

    Science.gov (United States)

    Han, Zheng; Cheng, Han; Parvani, Jenny G; Zhou, Zhuxian; Lu, Zheng-Rong

    2018-06-01

    Non-invasive early accurate detection of malignant breast cancer is paramount to the clinical management of the life-threatening disease. Here, we aim to test a small peptide targeted MRI contrast agent, ZD2-Gd(HP-DO3A), specific to an oncoprotein, extradomain-B fibronectin (EDB-FN), in the tumor microenvironment for MR molecular imaging of breast cancer. EDB-FN expression in 4T1 and MDA-MB-231 cancers was analyzed with quantitative real-time PCR and western blot. Primary and metastatic triple negative breast cancer mouse models were developed using 4T1 and MDA-MB-231 cells. Contrast-enhanced MRI was carried out to evaluate the use of ZD2-Gd(HP-DO3A) in detecting 4T1 and MDA-MB-231 primary and metastatic tumors. EDB-FN was abundantly expressed in the extracellular matrix (ECM) of both the primary and metastatic TNBC tumors. In T 1 -weighted MRI, ZD2-Gd(HP-DO3A) generated superior contrast enhancement in primary TNBC tumors than a nonspecific clinical agent Gd(HP-DO3A), during 30 min after contrast injection. ZD2-Gd(HP-DO3A) also produced a significant increase in contrast-to-noise ratio (CNR) of TNBC metastases, enabling sensitive localization and delineation of metastases that occulted in non-contrast-enhanced or Gd(HP-DO3A)-enhanced MRI. These findings potentiate the use of ZD2-Gd(HP-DO3A) for MR molecular imaging of malignant breast cancers to improve the healthcare of breast cancer patients. Magn Reson Med 79:3135-3143, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  13. Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

    Energy Technology Data Exchange (ETDEWEB)

    Thorek, Daniel L.J., E-mail: dthorek1@jhmi.edu [Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins School of Medicine, Baltimore, MD (United States); Kramer, Robin M. [Tri-Institutional Training Program in Laboratory Animal Medicine and Science, Memorial Sloan-Kettering Cancer Center (MSKCC), Weill Cornell Medical College, The Rockefeller University, New York, NY (United States); Chen, Qing; Jeong, Jeho; Lupu, Mihaela E. [Department of Medical Physics, MSKCC, New York, NY (United States); Lee, Alycia M.; Moynahan, Mary E.; Lowery, Maeve [Department of Medicine, MSKCC, New York, NY (United States); Ulmert, David [Molecular Pharmacology and Chemistry Program, MSKCC, New York, NY (United States); Department of Surgery (Urology), Skåne University Hospital, Malmö (Sweden); Zanzonico, Pat; Deasy, Joseph O.; Humm, John L. [Department of Medical Physics, MSKCC, New York, NY (United States); Russell, James, E-mail: russellj@mskcc.org [Department of Medical Physics, MSKCC, New York, NY (United States)

    2015-10-01

    Purpose: To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials: After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360° arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Results: Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions: This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response.

  14. Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

    International Nuclear Information System (INIS)

    Thorek, Daniel L.J.; Kramer, Robin M.; Chen, Qing; Jeong, Jeho; Lupu, Mihaela E.; Lee, Alycia M.; Moynahan, Mary E.; Lowery, Maeve; Ulmert, David; Zanzonico, Pat; Deasy, Joseph O.; Humm, John L.; Russell, James

    2015-01-01

    Purpose: To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials: After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360° arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Results: Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions: This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response

  15. Development of HER2-targeted nanobodies for molecular optical imaging and therapy of breast cancer

    NARCIS (Netherlands)

    Kijanka, M.M.

    2014-01-01

    Breast cancer is a complex disease and the most prevalent cancer in women worldwide. It has been estimated that 1 in 8 women and 1 in 1,000 men will develop breast cancer. Surgical-, chemical- and radiation based therapies are available to breast cancer patients. Early detection of cancer is crucial

  16. Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells.

    Science.gov (United States)

    Geninatti Crich, S; Cadenazzi, M; Lanzardo, S; Conti, L; Ruiu, R; Alberti, D; Cavallo, F; Cutrin, J C; Aime, S

    2015-04-21

    In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml(-1) (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation.

  17. Bispecific antibody complex pre-targeting and targeted delivery of polymer drug conjugates for imaging and therapy in dual human mammary cancer xenografts. Targeted polymer drug conjugates for cancer diagnosis and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Khaw, Ban-An; Gada, Keyur S.; Patil, Vishwesh; Panwar, Rajiv; Mandapati, Savitri [Northeastern University, Department of Pharmaceutical Sciences, Bouve College of Health Sciences, School of Pharmacy, Boston, MA (United States); Hatefi, Arash [Rutgers University, Department of Pharmaceutics, New Brunswick, NJ (United States); Majewski, Stan [West Virginia University, Department of Radiology, Morgantown, WV (United States); Weisenberger, Andrew [Thomas Jefferson National Accelerator Facility, Jefferson Lab, Newport News, VA (United States)

    2014-08-15

    Doxorubicin, a frontline chemotherapeutic agent, limited by its cardiotoxicity and other tissue toxicities, was conjugated to N-terminal DTPA-modified polyglutamic acid (D-Dox-PGA) to produce polymer pro-drug conjugates. D-Dox-PGA or Tc-99 m labeled DTPA-succinyl-polylysine polymers (DSPL) were targeted to HER2-positive human mammary carcinoma (BT-474) in a double xenografted SCID mouse model also hosting HER2-negative human mammary carcinoma (BT-20). After pretargeting with bispecific anti-HER2-affibody-anti-DTPA-Fab complexes (BAAC), anti-DTPA-Fab or only phosphate buffered saline, D-Dox-PGA or Tc-99 m DSPL were administered. Positive therapeutic control mice were injected with Dox alone at maximum tolerated dose (MTD). Only BT-474 lesions were visualized by gamma imaging with Tc-99 m-DSPL; BT-20 lesions were not. Therapeutic efficacy was equivalent in mice pretargeted with BAAC/targeted with D-Dox-PGA to mice treated only with doxorubicin. There was no total body weight (TBW) loss at three times the doxorubicin equivalent MTD with D-Dox-PGA, whereas mice treated with doxorubicin lost 10 % of TBW at 2 weeks and 16 % after the second MTD injection leading to death of all mice. Our cancer imaging and pretargeted therapeutic approaches are highly target specific, delivering very high specific activity reagents that may result in the development of a novel theranostic application. HER/2 neu specific affibody-anti-DTPA-Fab bispecific antibody pretargeting of HER2 positive human mammary xenografts enabled exquisite targeting of polymers loaded with radioisotopes for molecular imaging and doxorubicin for effective therapy without the associating non-tumor normal tissue toxicities. (orig.)

  18. Single-Domain Antibodies and the Promise of Modular Targeting in Cancer Imaging and Treatment

    Directory of Open Access Journals (Sweden)

    María Elena Iezzi

    2018-02-01

    Full Text Available Monoclonal antibodies and their fragments have significantly changed the outcome of cancer in the clinic, effectively inhibiting tumor cell proliferation, triggering antibody-dependent immune effector cell activation and complement mediated cell death. Along with a continued expansion in number, diversity, and complexity of validated tumor targets there is an increasing focus on engineering recombinant antibody fragments for lead development. Single-domain antibodies (sdAbs, in particular those engineered from the variable heavy-chain fragment (VHH gene found in Camelidae heavy-chain antibodies (or IgG2 and IgG3, are the smallest fragments that retain the full antigen-binding capacity of the antibody with advantageous properties as drugs. For similar reasons, growing attention is being paid to the yet smaller variable heavy chain new antigen receptor (VNAR fragments found in Squalidae. sdAbs have been selected, mostly from immune VHH libraries, to inhibit or modulate enzyme activity, bind soluble factors, internalize cell membrane receptors, or block cytoplasmic targets. This succinct review is a compilation of recent data documenting the application of engineered, recombinant sdAb in the clinic as epitope recognition “modules” to build monomeric, dimeric and multimeric ligands that target, tag and stall solid tumor growth in vivo. Size, affinity, specificity, and the development profile of sdAbs drugs are seemingly consistent with desirable clinical efficacy and safety requirements. But the hepatotoxicity of the tetrameric anti-DR5-VHH drug in patients with pre-existing anti-drug antibodies halted the phase I clinical trial and called for a thorough pre-screening of the immune and poly-specific reactivities of the sdAb leads.

  19. Deep Deconvolutional Neural Network for Target Segmentation of Nasopharyngeal Cancer in Planning Computed Tomography Images

    Directory of Open Access Journals (Sweden)

    Kuo Men

    2017-12-01

    Full Text Available BackgroundRadiotherapy is one of the main treatment methods for nasopharyngeal carcinoma (NPC. It requires exact delineation of the nasopharynx gross tumor volume (GTVnx, the metastatic lymph node gross tumor volume (GTVnd, the clinical target volume (CTV, and organs at risk in the planning computed tomography images. However, this task is time-consuming and operator dependent. In the present study, we developed an end-to-end deep deconvolutional neural network (DDNN for segmentation of these targets.MethodsThe proposed DDNN is an end-to-end architecture enabling fast training and testing. It consists of two important components: an encoder network and a decoder network. The encoder network was used to extract the visual features of a medical image and the decoder network was used to recover the original resolution by deploying deconvolution. A total of 230 patients diagnosed with NPC stage I or stage II were included in this study. Data from 184 patients were chosen randomly as a training set to adjust the parameters of DDNN, and the remaining 46 patients were the test set to assess the performance of the model. The Dice similarity coefficient (DSC was used to quantify the segmentation results of the GTVnx, GTVnd, and CTV. In addition, the performance of DDNN was compared with the VGG-16 model.ResultsThe proposed DDNN method outperformed the VGG-16 in all the segmentation. The mean DSC values of DDNN were 80.9% for GTVnx, 62.3% for the GTVnd, and 82.6% for CTV, whereas VGG-16 obtained 72.3, 33.7, and 73.7% for the DSC values, respectively.ConclusionDDNN can be used to segment the GTVnx and CTV accurately. The accuracy for the GTVnd segmentation was relatively low due to the considerable differences in its shape, volume, and location among patients. The accuracy is expected to increase with more training data and combination of MR images. In conclusion, DDNN has the potential to improve the consistency of contouring and streamline radiotherapy

  20. The Role of Seminal Vesicle Motion in Target Margin Assessment for Online Image-Guided Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Liang Jian; Wu Qiuwen; Yan Di

    2009-01-01

    Purpose: For patients with intermediate- and high-risk prostate cancer, the seminal vesicles (SVs) are included in the clinical target volume (CTV). The purposes of this study are to investigate interfraction motion characteristics of the SVs and determine proper margins for online computed tomography image guidance. Methods and Materials: Twenty-four patients, each with 16 daily helical computed tomography scans, were included in this study. A binary image mask was used for image registration to determine daily organ motion. Two online image-guided radiotherapy strategies (prostate only and prostate + SVs) were simulated in a hypofractionated scheme. Three margin designs were studied for both three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (IMRT). In prostate-only guidance, Margin A was uniformly applied to the whole CTV, and Margin B was applied to the SVs with a fixed 3-mm prostate margin. In prostate plus SV guidance, Margin C was uniformly applied to the CTV. The minimum margins were sought to satisfy the criterion that minimum cumulative CTV dose be more than those of the planning target volume in the plan for greater than 95% of patients. Results: The prostate and SVs move significantly more in the anterior-posterior and superior-inferior than right-left directions. The anterior-posterior motion of the prostate and SVs correlated (R 2 = 0.7). The SVs move significantly more than the prostate. The minimum margins found were 2.5 mm for three-dimensional conformal radiotherapy and 4.5, 4.5, and 3.0 mm for Margins A, B, and C for IMRT, respectively. Margins for IMRT were larger, but the irradiated volume and doses to critical structures were smaller. Minimum margins of 4.5 mm to the SVs and 3 mm to the prostate are recommended for IMRT with prostate-only guidance. Conclusions: The SVs move independently from the prostate gland, and additional margins are necessary for image-guided radiotherapy

  1. Localization Accuracy of the Clinical Target Volume During Image-Guided Radiotherapy of Lung Cancer

    International Nuclear Information System (INIS)

    Hugo, Geoffrey D.; Weiss, Elisabeth; Badawi, Ahmed; Orton, Matthew

    2011-01-01

    Purpose: To evaluate the position and shape of the originally defined clinical target volume (CTV) over the treatment course, and to assess the impact of gross tumor volume (GTV)-based online computed tomography (CT) guidance on CTV localization accuracy. Methods and Materials: Weekly breath-hold CT scans were acquired in 17 patients undergoing radiotherapy. Deformable registration was used to propagate the GTV and CTV from the first weekly CT image to all other weekly CT images. The on-treatment CT scans were registered rigidly to the planning CT scan based on the GTV location to simulate online guidance, and residual error in the CTV centroids and borders was calculated. Results: The mean GTV after 5 weeks relative to volume at the beginning of treatment was 77% ± 20%, whereas for the prescribed CTV, it was 92% ± 10%. The mean absolute residual error magnitude in the CTV centroid position after a GTV-based localization was 2.9 ± 3.0 mm, and it varied from 0.3 to 20.0 mm over all patients. Residual error of the CTV centroid was associated with GTV regression and anisotropy of regression during treatment (p = 0.02 and p = 0.03, respectively; Spearman rank correlation). A residual error in CTV border position greater than 2 mm was present in 77% of patients and 50% of fractions. Among these fractions, residual error of the CTV borders was 3.5 ± 1.6 mm (left-right), 3.1 ± 0.9 mm (anterior-posterior), and 6.4 ± 7.5 mm (superior-inferior). Conclusions: Online guidance based on the visible GTV produces substantial error in CTV localization, particularly for highly regressing tumors. The results of this study will be useful in designing margins for CTV localization or for developing new online CTV localization strategies.

  2. Calculation of Lung Cancer Volume of Target Based on Thorax Computed Tomography Images using Active Contour Segmentation Method for Treatment Planning System

    Science.gov (United States)

    Patra Yosandha, Fiet; Adi, Kusworo; Edi Widodo, Catur

    2017-06-01

    In this research, calculation process of the lung cancer volume of target based on computed tomography (CT) thorax images was done. Volume of the target calculation was done in purpose to treatment planning system in radiotherapy. The calculation of the target volume consists of gross tumor volume (GTV), clinical target volume (CTV), planning target volume (PTV) and organs at risk (OAR). The calculation of the target volume was done by adding the target area on each slices and then multiply the result with the slice thickness. Calculations of area using of digital image processing techniques with active contour segmentation method. This segmentation for contouring to obtain the target volume. The calculation of volume produced on each of the targets is 577.2 cm3 for GTV, 769.9 cm3 for CTV, 877.8 cm3 for PTV, 618.7 cm3 for OAR 1, 1,162 cm3 for OAR 2 right, and 1,597 cm3 for OAR 2 left. These values indicate that the image processing techniques developed can be implemented to calculate the lung cancer target volume based on CT thorax images. This research expected to help doctors and medical physicists in determining and contouring the target volume quickly and precisely.

  3. Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging and Fusion Guided Targeted Biopsy Evaluated by Transperineal Template Saturation Prostate Biopsy for the Detection and Characterization of Prostate Cancer.

    Science.gov (United States)

    Mortezavi, Ashkan; Märzendorfer, Olivia; Donati, Olivio F; Rizzi, Gianluca; Rupp, Niels J; Wettstein, Marian S; Gross, Oliver; Sulser, Tullio; Hermanns, Thomas; Eberli, Daniel

    2018-02-21

    We evaluated the diagnostic accuracy of multiparametric magnetic resonance imaging and multiparametric magnetic resonance imaging/transrectal ultrasound fusion guided targeted biopsy against that of transperineal template saturation prostate biopsy to detect prostate cancer. We retrospectively analyzed the records of 415 men who consecutively presented for prostate biopsy between November 2014 and September 2016 at our tertiary care center. Multiparametric magnetic resonance imaging was performed using a 3 Tesla device without an endorectal coil, followed by transperineal template saturation prostate biopsy with the BiopSee® fusion system. Additional fusion guided targeted biopsy was done in men with a suspicious lesion on multiparametric magnetic resonance imaging, defined as Likert score 3 to 5. Any Gleason pattern 4 was defined as clinically significant prostate cancer. The detection rates of multiparametric magnetic resonance imaging and fusion guided targeted biopsy were compared with the detection rate of transperineal template saturation prostate biopsy using the McNemar test. We obtained a median of 40 (range 30 to 55) and 3 (range 2 to 4) transperineal template saturation prostate biopsy and fusion guided targeted biopsy cores, respectively. Of the 124 patients (29.9%) without a suspicious lesion on multiparametric magnetic resonance imaging 32 (25.8%) were found to have clinically significant prostate cancer on transperineal template saturation prostate biopsy. Of the 291 patients (70.1%) with a Likert score of 3 to 5 clinically significant prostate cancer was detected in 129 (44.3%) by multiparametric magnetic resonance imaging fusion guided targeted biopsy, in 176 (60.5%) by transperineal template saturation prostate biopsy and in 187 (64.3%) by the combined approach. Overall 58 cases (19.9%) of clinically significant prostate cancer would have been missed if fusion guided targeted biopsy had been performed exclusively. The sensitivity of

  4. Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

    Directory of Open Access Journals (Sweden)

    Bwatanglang IB

    2016-01-01

    exhibit any toxicity toward the human breast cell line MCF-10 (noncancer and the breast cancer cell lines (MCF-7 and MDA-MB-231 up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we hypothesized that due to the nontoxic nature of the composite, the as-synthesized nanoparticulate system can be used as a promising candidate for theranostic applications, especially for a simultaneous targeted drug delivery and cellular imaging. Keywords: Mn:ZnS, quantum dots, theranostics, folic acid, cancer diagnosis, fluorescence imaging

  5. Fluoridated hydroxyapatite: Eu3+ nanorods-loaded folate-conjugated D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) micelles for targeted imaging of cancer cells

    Science.gov (United States)

    Wan, Dong; Liu, Weijiao; Wang, Lei; Wang, Hao; Pan, Jie

    2016-03-01

    In this study, fluoridated hydroxyapatite: Eu3+ nanorod-loaded folate-conjugated TPGS micelles were prepared by thin-film hydration. The findings in this study demonstrate that micelles show improved dispersion, high stability, and excellent fluorescent property in aqueous solutions, suitable for targeted imaging of cancer cells with over-expressing folate receptors on their surface. The micelles designed in this study will be a promising tool for early detection of cancer.

  6. Image-based phenotypic screening for breast cancer metastasis drug target discovery

    NARCIS (Netherlands)

    Fokkelman, M.

    2017-01-01

    The main aim of this thesis was to unravel the signaling and regulatory networks that drive tumor cell migration during breast cancer metastasis. Understanding how tumor cells migrate, how this process is differentially regulated, and how this highly heterogeneous and plastic behavior is

  7. VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    Science.gov (United States)

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-07-01

    Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p ultrasound imaging was significantly (p ultrasound imaging in hens with OVCA were positively correlated with increased (p therapeutics. © The Author(s) 2014.

  8. Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study

    OpenAIRE

    Reuveni, Tobi; Motiei, Menachem; Romman, Zimam; Popovtzer, Aron; Popovtzer, Rachela

    2011-01-01

    Tobi Reuveni1, Menachem Motiei1, Zimam Romman2, Aron Popovtzer3, Rachela Popovtzer11Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-ilan University, Ramat Gan, 2GE HealthCare, Tirat Hacarmel, 3Department of Otorhinolaryngology, Head and Neck Surgery and Onology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, IsraelAbstract: In recent years, advances in molecular biology and cancer research have led to the identification of sensitiv...

  9. Early Detection of Ovarian Cancer by Contrast-Enhanced Ultrasound-Targeted Imaging

    Science.gov (United States)

    2013-09-01

    nickel chloride as reported earlier.17 Sections were then counter- stained with hematoxylin, dehydrated, and covered. In con- trol staining, first...cell) in the first step to confirm ovarian epithelial cells and for IL-16 in the second step using DAB and DAB and nickel chloride, respectively...cells. J Allergy Clin Immunol. 1996;97:443. 22. Zhang L, Sun SK, Shi LX, et al. Serum cytokine profiling of prostate cancer and benign prostatic

  10. IMPACT: Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatments, and Therapeutic Modalities

    Science.gov (United States)

    2016-04-01

    clinical studies for a novel PET imaging tracer in the development process is to evaluate the tracer in nonhuman primates. During this study, the...recruitment process at Fifth Ward Enrichment Center was assisted by the program’s Executive Director; a school counselor at M.R. Wood assisted in...Award Number: W81XWH-05-2-0027 TITLE: IMPACT: Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets

  11. GRP-R expression in breast cancer as target for nuclear imaging and therapy, correlation with ER

    International Nuclear Information System (INIS)

    Dalm, S.U.; Melis, M.; Sieuwerts, A.M.; Martens, J.W.M.; Jong, M. de

    2015-01-01

    Full text of publication follows. Introduction: Breast cancer (BC) is a complex and heterogeneous disease: several molecular characteristics reflect subtypes, partly overlapping with therapeutic targets. Examples include the expression of the oestrogen receptor (ER), expressed in approximately 75 % of all breast cancer cases. Currently mammography, MRI, 99m Tc-Sestamibi scintigraphy, and 18 F-FDG PET are commonly used for diagnostic imaging to accurately localize BC. Since it has been reported that the gastrin releasing peptide receptor (GRP-R) is expressed in BC, targeting this receptor with radiolabeled GRP analogues might offer opportunities for SPECT/CT or PET/CT imaging as well as radionuclide therapy in BC. In this study GRP-R expression was determined in human BC specimens and BC cell lines and correlated with ER status. Methods: GRP-R mRNA levels of 90 human breast cancer specimens, with known ER status (48 ER-positive and 42 ER-negative) were determined using qRT-PCR in a Taqman Gene expression assay. Furthermore a panel of 21 BC cell lines characterized for ER expression (13 ER-positive, 8 ER-negative) was analysed for GRP-R expression at the protein level. Internalisation studies were performed with 10-9 M 111 In-AMBA (an receptor-agonist GRP analogue) for 1 hour and 15 minutes at 37 C. degrees. Thirteen of these BC cell lines were also analyzed for GRP-R expression at mRNA level using qRT-PCR. Results: Clinical BC specimens with high GRP-R mRNA level were all ER-positive, resulting in a significant positive correlation (p=0.03). Fifty-two percent of the analyzed BC cell lines showed the ability to internalize 111 In-AMBA, although high variation between cell lines was observed. GRP-R mRNA levels of the BC cell lines significantly correlated with the internalisation rate (p=0.0003), indicating that the amount of internalized 111 In-AMBA is partly determined by the level of receptor expression. However, no correlation was found between ER status and GRP

  12. Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy.

    Science.gov (United States)

    Bwatanglang, Ibrahim Birma; Mohammad, Faruq; Yusof, Nor Azah; Abdullah, Jaafar; Hussein, Mohd Zobir; Alitheen, Noorjahan Banu; Abu, Nadiah

    2016-01-01

    In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange-red fluorescence around 600 nm and investigated to the highest intensity at Mn(2+) doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we

  13. Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

    Science.gov (United States)

    Bwatanglang, Ibrahim Birma; Mohammad, Faruq; Yusof, Nor Azah; Abdullah, Jaafar; Hussein, Mohd Zobir; Alitheen, Noorjahan Banu; Abu, Nadiah

    2016-01-01

    In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange–red fluorescence around 600 nm and investigated to the highest intensity at Mn2+ doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we

  14. In vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent

    Science.gov (United States)

    2016-11-01

    algorithms have been developed to de- convolute the individual chromophore PA images. Five dyes (IRDye800CW, AlexaFluor750, Cy7-NHS- ester, Cy7...specific biomarker. Thi the PA signal spectrum of endogenous or exogenous dye components and algorithms have been developed to de-convolve the... incubated in a 4 µM solution of the TMIA in PBS, washed thrice in PBS by centrifugation and resuspension, and Fig. 5. Sensitivity of IRDye800CW using

  15. Value of Magnetic Resonance Imaging Without or With Applicator in Place for Target Definition in Cervix Cancer Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Pötter, Richard [Department of Radiotherapy, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria); Federico, Mario [Department of Radiotherapy, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Department of Radiation Oncology, Gran Canaria University Hospital, Las Palmas de Gran Canaria (Spain); Sturdza, Alina [Department of Radiotherapy, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Fotina, Irina [Department of Radiotherapy, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Institute of Physics and Technology, Tomsk Polytechnic University, Tomsk Oblast (Russian Federation); Hegazy, Neamat [Department of Radiotherapy, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Department of Clinical Oncology, Medical University of Alexandria, Alexandria (Egypt); Schmid, Maximilian; Kirisits, Christian [Department of Radiotherapy, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria); Nesvacil, Nicole, E-mail: nicole.nesvacil@meduniwien.ac.at [Department of Radiotherapy, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria)

    2016-03-01

    Purpose: To define, in the setting of cervical cancer, to what extent information from additional pretreatment magnetic resonance imaging (MRI) without the brachytherapy applicator improves conformity of CT-based high-risk clinical target volume (CTV{sub HR}) contours, compared with the MRI for various tumor stages (International Federation of Gynecology and Obstetrics [FIGO] stages I-IVA). Methods and Materials: The CTV{sub HR} was contoured in 39 patients with cervical cancer (FIGO stages I-IVA) (1) on CT images based on clinical information (CTV{sub HR}-CT{sub Clinical}) alone; and (2) using an additional MRI before brachytherapy, without the applicator (CTV{sub HR}-CT{sub pre-BT} {sub MRI}). The CT contours were compared with reference contours on MRI with the applicator in place (CTV{sub HR}-MRI{sub ref}). Width, height, thickness, volumes, and topography were analyzed. Results: The CT-MRI{sub ref} differences hardly varied in stage I tumors (n=8). In limited-volume stage IIB and IIIB tumors (n=19), CTV{sub HR}-CT{sub pre-BT} {sub MRI}–MRI{sub ref} volume differences (2.6 cm{sup 3} [IIB], 7.3 cm{sup 3} [IIIB]) were superior to CTV{sub HR}-CT{sub Clinical}–MRI{sub ref} (11.8 cm{sup 3} [IIB], 22.9 cm{sup 3} [IIIB]), owing to significant improvement of height and width (P<.05). In advanced disease (n=12), improved agreement with MR volume, width, and height was achieved for CTV{sub HR}-CT{sub pre-BT} {sub MRI}. In 5 of 12 cases, MRI{sub ref} contours were partly missed on CT. Conclusions: Pre-BT MRI helps to define CTV{sub HR} before BT implantation appropriately, if only CT images with the applicator in place are available for BT planning. Significant improvement is achievable in limited-volume stage IIB and IIIB tumors. In more advanced disease (extensive IIB to IVA), improvement of conformity is possible but may be associated with geographic misses. Limited impact on precision of CTV{sub HR}-CT is expected in stage IB tumors.

  16. Imaging efficacy of a targeted imaging agent for fluorescence endoscopy

    Science.gov (United States)

    Healey, A. J.; Bendiksen, R.; Attramadal, T.; Bjerke, R.; Waagene, S.; Hvoslef, A. M.; Johannesen, E.

    2008-02-01

    Colorectal cancer is a major cause of cancer death. A significant unmet clinical need exists in the area of screening for earlier and more accurate diagnosis and treatment. We have identified a fluorescence imaging agent targeted to an early stage molecular marker for colorectal cancer. The agent is administered intravenously and imaged in a far red imaging channel as an adjunct to white light endoscopy. There is experimental evidence of preclinical proof of mechanism for the agent. In order to assess potential clinical efficacy, imaging was performed with a prototype fluorescence endoscope system designed to produce clinically relevant images. A clinical laparoscope system was modified for fluorescence imaging. The system was optimised for sensitivity. Images were recorded at settings matching those expected with a clinical endoscope implementation (at video frame rate operation). The animal model was comprised of a HCT-15 xenograft tumour expressing the target at concentration levels expected in early stage colorectal cancer. Tumours were grown subcutaneously. The imaging agent was administered intravenously at a dose of 50nmol/kg body weight. The animals were killed 2 hours post administration and prepared for imaging. A 3-4mm diameter, 1.6mm thick slice of viable tumour was placed over the opened colon and imaged with the laparoscope system. A receiver operator characteristic analysis was applied to imaging results. An area under the curve of 0.98 and a sensitivity of 87% [73, 96] and specificity of 100% [93, 100] were obtained.

  17. Immunotherapy Targets Common Cancer Mutation

    Science.gov (United States)

    In a study of an immune therapy for colorectal cancer that involved a single patient, researchers identified a method for targeting the cancer-causing protein produced by a mutant form of the KRAS gene.

  18. Body image mediates the effect of cancer-related stigmatization on depression: A new target for intervention.

    Science.gov (United States)

    Esser, Peter; Mehnert, Anja; Johansen, Christoffer; Hornemann, Beate; Dietz, Andreas; Ernst, Jochen

    2018-01-01

    Because cancer-related stigmatization is prevalent but difficult to change, research on its impact on psychological burden and respective intervening variables is needed. Therefore, we investigated the effect of stigmatization on depressive symptomatology and whether body image mediates this relationship. This bicentric study assessed patients of 4 major tumor entities. We measured stigmatization (SIS-D), depressive symptomatology (PHQ-9), and body image (FKB-20). Applying multiple mediator analyses, we calculated the total effect of stigmatization on depressive symptomatology and the indirect effects exerted via the 2 body image scales rejecting body evaluation and vital body dynamics. Among the 858 cancer patients recruited (breast: n = 297; prostate: n = 268; colorectal: n = 168; lung: n = 125), stigmatization showed total effects on depressive symptomatology across all stigma dimensions (all p total sample  Body image as a whole was shown to mediate the effect across all samples (γ total sample  = .04, 95%-CI: 0.03-0.06). Among the total sample and prostate cancer patients, the mediating effect of rejecting body evaluation was significantly larger than the effect of vital body dynamics (d total sample  = .02, 95%-CI: 0.01-0.04). Perceived stigmatization is an important and generalizable risk factor for depressive symptomatology among cancer patients. Apart from interventions addressing stigmatization, improving body image could additionally help to reduce the psychological burden in stigmatized patients. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Targeted molecular imaging

    International Nuclear Information System (INIS)

    Kim, E. Edmund

    2003-01-01

    Molecular imaging aims to visualize the cellular and molecular processes occurring in living tissues, and for the imaging of specific molecules in vivo, the development of reporter probes and dedicated imaging equipment is most important. Reporter genes can be used to monitor the delivery and magnitude of therapeutic gene transfer, and the time variation involved. Imaging technologies such as micro-PET, SPECT, MRI and CT, as well as optical imaging systems, are able to non-invasively detect, measure, and report the simultaneous expression of multiple meaningful genes. It is believed that recent advances in reporter probes, imaging technologies and gene transfer strategies will enhance the effectiveness of gene therapy trials

  20. Design and construction of multifunctional hyperbranched polymers coated magnetite nanoparticles for both targeting magnetic resonance imaging and cancer therapy.

    Science.gov (United States)

    Mashhadi Malekzadeh, Asemeh; Ramazani, Ali; Tabatabaei Rezaei, Seyed Jamal; Niknejad, Hassan

    2017-03-15

    Magnetic drug targeting is a drug delivery strategy that can be used to improve the therapeutic efficiency on tumor cells and reduce the side effects on normal cells and tissues. The aim in this study is designing a novel multifunctional drug delivery system based on superparamagnetic nanoparticles for cancer therapy. Magnetic nanoparticles were synthesized by coprecipitation of iron oxide followed by coating with poly citric acid (PCA) dendritic macromolecules via bulk polymerization strategy. It was further surface-functionalized with poly(ethylene glycol) (PEG) and then to achieve tumor cell targeting property, folic acid was further incorporated to the surface of prepared carriers via a facile coupling reaction between the hydroxyl end group of the PEG and the carboxyl group of folic acid. The so prepared nanocarriers (Fe 3 O 4 @PCA-PEG-FA) were characterized by X-ray diffraction, TEM, TGA, FT-IR, DLS and VSM techniques. The room temperature VSM measurements showed that magnetic particles were superparamagnetic. Transmission electron microscopy and dynamic light scattering were also performed which revealed that size of nanocarriers was lying in the range of 10-49nm. Quercetin loading and release profiles of prepared nanocarriers showed that up to 83% of loaded drug was released in 250h. Fluorescent microscopy showed that the cellular uptake by folate receptor-overexpressing HeLa cells of the quercetin-loaded Fe 3 O 4 @PCA-PEG-FA nanoparticles was higher than that of non-folate conjugated nanoparticles. Thus, folate conjugation significantly increased nanoparticle cytotoxicity. Also, T 2 -weighted MRI images of Fe 3 O 4 @PCA-PEG-FA nanoparticles showed that the magnetic resonance signal is enhanced significantly with increasing nanoparticle concentration in water and they also served as MRI contrast agents with relaxivities of 3.4mM -1 s -1 (r 1 ) and 99.8mM -1 s -1 (r 2 ). The results indicate that this multifunctional nanocarrier is a significant breakthrough

  1. Will nanotechnology influence targeted cancer therapy?

    Science.gov (United States)

    Grimm, Jan; Scheinberg, David A

    2011-04-01

    The rapid development of techniques that enable synthesis (and manipulation) of matter on the nanometer scale and the development of new nanomaterials will play a large role in disease diagnosis and treatment, specifically in targeted cancer therapy. Targeted nanocarriers are an intriguing means to selectively deliver high concentrations of cytotoxic agents or imaging labels directly to the cancer site. Often, solubility issues and an unfavorable biodistribution can result in a suboptimal response of novel agents even though they are very potent. New nanoparticulate formulations allow simultaneous imaging and therapy ("theranostics"), which can provide a realistic means for the clinical implementation of such otherwise suboptimal formulations. In this review, we did not attempt to provide a complete overview of the rapidly enlarging field of nanotechnology in cancer; rather, we presented properties specific to nanoparticles and examples of their uses, which show their importance for targeted cancer therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Anti-HER2 antibody and ScFvEGFR-conjugated antifouling magnetic iron oxide nanoparticles for targeting and magnetic resonance imaging of breast cancer

    Directory of Open Access Journals (Sweden)

    Chen H

    2013-10-01

    Full Text Available Hongwei Chen,1,* Liya Wang,1,2,* Qiqi Yu,1,2 Weiping Qian,3 Diana Tiwari,1 Hong Yi,4 Andrew Y Wang,5 Jing Huang,1,2 Lily Yang,3 Hui Mao1,2 1Department of Radiology and Imaging Sciences, 2Center for Systems Imaging, 3Department of Surgery, Emory University School of Medicine, 4Robert Apkarian Electron Microscopy Core, Emory University, Atlanta, GA, 5Ocean NanoTech LLC, Springdale, AK, USA *These authors contributed equally to this work Abstract: Antifouling magnetic iron oxide nanoparticles (IONPs coated with block copolymer poly(ethylene oxide-block-poly(γ-methacryloxypropyltrimethoxysilane (PEO-b-PγMPS were investigated for improving cell targeting by reducing nonspecific uptake. Conjugation of a HER2 antibody, Herceptin®, or a single chain fragment (ScFv of antibody against epidermal growth factor receptor (ScFvEGFR to PEO-b-PγMPS-coated IONPs resulted in HER2-targeted or EGFR-targeted IONPs (anti-HER2-IONPs or ScFvEGFR-IONPs. The anti-HER2-IONPs bound specifically to SK-BR-3, a HER2-overexpressing breast cancer cell line, but not to MDA-MB-231, a HER2-underexpressing cell line. On the other hand, the ScFvEGFR-IONPs showed strong reactivity with MDA-MB-231, an EGFR-positive human breast cancer cell line, but not with MDA-MB-453, an EGFR-negative human breast cancer cell line. Transmission electron microscopy revealed internalization of the receptor-targeted nanoparticles by the targeted cancer cells. In addition, both antibody-conjugated and non-antibody-conjugated IONPs showed reduced nonspecific uptake by RAW264.7 mouse macrophages in vitro. The developed IONPs showed a long blood circulation time (serum half-life 11.6 hours in mice and low accumulation in both the liver and spleen. At 24 hours after systemic administration of ScFvEGFR-IONPs into mice bearing EGFR-positive breast cancer 4T1 mouse mammary tumors, magnetic resonance imaging revealed signal reduction in the tumor as a result of the accumulation of the targeted IONPs

  3. Highly biocompatible TiO2:Gd3+ nano-contrast agent with enhanced longitudinal relaxivity for targeted cancer imaging

    Science.gov (United States)

    Chandran, Parwathy; Sasidharan, Abhilash; Ashokan, Anusha; Menon, Deepthy; Nair, Shantikumar; Koyakutty, Manzoor

    2011-10-01

    We report the development of a novel magnetic nano-contrast agent (nano-CA) based on Gd3+ doped amorphous TiO2 of size ~25 nm, exhibiting enhanced longitudinal relaxivity (r1) and magnetic resonance (MR) contrasting together with excellent biocompatibility. Quantitative T1 mapping of phantom samples using a 1.5 T clinical MR imaging system revealed that the amorphous phase of doped titania has the highest r1 relaxivity which is ~2.5 fold higher than the commercially used CA Magnevist™. The crystalline (anatase) samples formed by air annealing at 250 °C and 500 °C showed significant reduction in r1 values and MR contrast, which is attributed to the loss of proton-exchange contribution from the adsorbed water and atomic re-arrangement of Gd3+ ions in the crystalline host lattice. Nanotoxicity studies including cell viability, plasma membrane integrity, reactive oxygen stress and expression of pro-inflammatory cytokines, performed on human primary endothelial cells (HUVEC), human blood derived peripheral blood mononuclear cells (PBMC) and nasopharyngeal epidermoid carcinoma (KB) cell line showed excellent biocompatibility up to relatively higher doses of 200 μg ml-1. The potential of this nano-CA to cause hemolysis, platelet aggregation and plasma coagulation were studied using human peripheral blood samples and found no adverse effects, illustrating the possibility of the safe intravenous administration of these agents for human applications. Furthermore, the ability of these agents to specifically detect cancer cells by targeting molecular receptors on the cell membrane was demonstrated on folate receptor (FR) positive oral carcinoma (KB) cells, where the folic acid conjugated nano-CA showed receptor specific accumulation on cell membrane while leaving the normal fibroblast cells (L929) unstained. This study reveals that the Gd3+ doped amorphous TiO2 nanoparticles having enhanced magnetic resonance contrast and high biocompatibility is a promising candidate for

  4. Ultrasound Molecular Imaging of the Breast Cancer Neovasculature using Engineered Fibronectin Scaffold Ligands: A Novel Class of Targeted Contrast Ultrasound Agent.

    Science.gov (United States)

    Abou-Elkacem, Lotfi; Wilson, Katheryne E; Johnson, Sadie M; Chowdhury, Sayan M; Bachawal, Sunitha; Hackel, Benjamin J; Tian, Lu; Willmann, Jürgen K

    2016-01-01

    Molecularly-targeted microbubbles (MBs) are increasingly being recognized as promising contrast agents for oncological molecular imaging with ultrasound. With the detection and validation of new molecular imaging targets, novel binding ligands are needed that bind to molecular imaging targets with high affinity and specificity. In this study we assessed a novel class of potentially clinically translatable MBs using an engineered 10(th) type III domain of human-fibronectin (MB-FN3VEGFR2) scaffold-ligand to image VEGFR2 on the neovasculature of cancer. The in vitro binding of MB-FN3VEGFR2 to a soluble VEGFR2 was assessed by flow-cytometry (FACS) and binding to VEGFR2-expressing cells was assessed by flow-chamber cell attachment studies under flow shear stress conditions. In vivo binding of MB-FN3VEGFR2 was tested in a transgenic mouse model (FVB/N Tg(MMTV/PyMT634Mul) of breast cancer and control litter mates with normal mammary glands. In vitro FACS and flow-chamber cell attachment studies showed significantly (Pbreast cancer compared to normal breast tissue. Ex vivo immunofluorescence-analysis showed significantly (Pbreast cancer compared to normal mammary tissue. Our results suggest that MBs coupled to FN3-scaffolds can be designed and used for USMI of breast cancer neoangiogenesis. Due to their small size, stability, solubility, the lack of glycosylation and disulfide bonds, FN3-scaffolds can be recombinantly produced with the advantage of generating small, high affinity ligands in a cost efficient way for USMI.

  5. Targeting Cancer Protein Profiles with Split-Enzyme Reporter Fragments to Achieve Chemical Resolution for Molecular Imaging

    Science.gov (United States)

    2014-11-01

    SPIE BiOS: Biomedical Optics Symposium. • Optical imaging of targeted beta-galactosidase in brain tumors to detect EGFR levels. (2015) Nanotech ...the coordinated expression of cell surface receptors in glioblastomas. World Molecular Imaging Congress. Best Poster in Category. • Agnes, R.S...of stock Cy5.5- labeled peptide solutions in dimethyl sulfoxide (DMSO) was determined by UV-Vis spectrometry [Cy5.5 molar extinction coefficient is

  6. In-Bore 3-T MR-guided Transrectal Targeted Prostate Biopsy: Prostate Imaging Reporting and Data System Version 2-based Diagnostic Performance for Detection of Prostate Cancer.

    Science.gov (United States)

    Tan, Nelly; Lin, Wei-Chan; Khoshnoodi, Pooria; Asvadi, Nazanin H; Yoshida, Jeffrey; Margolis, Daniel J A; Lu, David S K; Wu, Holden; Sung, Kyung Hyun; Lu, David Y; Huang, Jaioti; Raman, Steven S

    2017-04-01

    Purpose To determine the diagnostic yield of in-bore 3-T magnetic resonance (MR) imaging-guided prostate biopsy and stratify performance according to Prostate Imaging Reporting and Data System (PI-RADS) versions 1 and 2. Materials and Methods This study was HIPAA compliant and institution review board approved. In-bore 3-T MR-guided prostate biopsy was performed in 134 targets in 106 men who (a) had not previously undergone prostate biopsy, (b) had prior negative biopsy findings with increased prostate-specific antigen (PSA) level, or (c) had a prior history of prostate cancer with increasing PSA level. Clinical, diagnostic 3-T MR imaging was performed with in-bore guided prostate biopsy, and pathology data were collected. The diagnostic yields of MR-guided biopsy per patient and target were analyzed, and differences between biopsy targets with negative and positive findings were determined. Results of logistic regression and areas under the curve were compared between PI-RADS versions 1 and 2. Results Prostate cancer was detected in 63 of 106 patients (59.4%) and in 72 of 134 targets (53.7%) with 3-T MR imaging. Forty-nine of 72 targets (68.0%) had clinically significant cancer (Gleason score ≥ 7). One complication occurred (urosepsis, 0.9%). Patients who had positive target findings had lower apparent diffusion coefficient values (875 × 10 -6 mm 2 /sec vs 1111 × 10 -6 mm 2 /sec, respectively; P PSA density (0.16 vs 0.10, respectively; P PI-RADS version 2 category 3-5 scores when compared with patients with negative target findings. MR targets with PI-RADS version 2 category 2, 3, 4, and 5 scores had a positive diagnostic yield of three of 23 (13.0%), six of 31 (19.4%), 39 of 50 (78.0%), and 24 of 29 (82.8%) targets, respectively. No differences were detected in areas under the curve for PI-RADS version 2 versus 1. Conclusion In-bore 3-T MR-guided biopsy is safe and effective for prostate cancer diagnosis when stratified according to PI-RADS versions 1 and 2

  7. Synthesis and characterization of Bombesin-superparamagnetic iron oxide nanoparticles as a targeted contrast agent for imaging of breast cancer using MRI

    International Nuclear Information System (INIS)

    Jafari, Atefeh; Shayesteh, Saber Farjami; Salouti, Mojtaba; Heidari, Zahra; Rajabi, Ahmad Bitarafan; Boustani, Komail; Nahardani, Ali

    2015-01-01

    The targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent may facilitate their accumulation in cancer cells and enhance the sensitivity of MR imaging. In this study, SPIONs coated with dextran (DSPIONs) were conjugated with bombesin (BBN) to produce a targeting contrast agent for detection of breast cancer using MRI. X-ray diffraction, transmission electron microscopy, and vibrating sample magnetometer analyses indicated the formation of dextran-coated superparamagnetic iron oxide nanoparticles with an average size of 6.0 ± 0.5 nm. Fourier transform infrared spectroscopy confirmed the conjugation of the BBN with the DSPIONs. A stability study proved the high optical stability of DSPION–BBN in human blood serum. DSPION–BBN biocompatibility was confirmed by cytotoxicity evaluation. A binding study showed the targeting ability of DSPION–BBN to bind to T47D breast cancer cells overexpressing gastrin-releasing peptide (GRP) receptors. T 2 -weighted and T 2 *-weighted color map MR images were acquired. The MRI study indicated that the DSPION–BBN possessed good diagnostic ability as a GRP-specific contrast agent, with appropriate signal reduction in T 2 *-weighted color map MR images in mice with breast tumors. (paper)

  8. Synthesis and characterization of Bombesin-superparamagnetic iron oxide nanoparticles as a targeted contrast agent for imaging of breast cancer using MRI

    Science.gov (United States)

    Jafari, Atefeh; Salouti, Mojtaba; Farjami Shayesteh, Saber; Heidari, Zahra; Bitarafan Rajabi, Ahmad; Boustani, Komail; Nahardani, Ali

    2015-02-01

    The targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent may facilitate their accumulation in cancer cells and enhance the sensitivity of MR imaging. In this study, SPIONs coated with dextran (DSPIONs) were conjugated with bombesin (BBN) to produce a targeting contrast agent for detection of breast cancer using MRI. X-ray diffraction, transmission electron microscopy, and vibrating sample magnetometer analyses indicated the formation of dextran-coated superparamagnetic iron oxide nanoparticles with an average size of 6.0 ± 0.5 nm. Fourier transform infrared spectroscopy confirmed the conjugation of the BBN with the DSPIONs. A stability study proved the high optical stability of DSPION-BBN in human blood serum. DSPION-BBN biocompatibility was confirmed by cytotoxicity evaluation. A binding study showed the targeting ability of DSPION-BBN to bind to T47D breast cancer cells overexpressing gastrin-releasing peptide (GRP) receptors. T2-weighted and T2*-weighted color map MR images were acquired. The MRI study indicated that the DSPION-BBN possessed good diagnostic ability as a GRP-specific contrast agent, with appropriate signal reduction in T2*-weighted color map MR images in mice with breast tumors.

  9. Designed Synthesis of Au/Fe3O4@C Janus Nanoparticles for Dual-Modal Imaging and Actively Targeted Chemo-Photothermal Synergistic Therapy of Cancer Cells.

    Science.gov (United States)

    Zhang, Qi; Zhang, Lingyu; Li, Shengnan; Chen, Xiangjun; Zhang, Manjie; Wang, Tingting; Li, Lu; Wang, Chungang

    2017-12-06

    Elaborately designed novel multifunctional Janus nanoparticles (JNPs) have attracted considerable attention owing to their anisotropic surface properties and various functionalities that allow them to house several components for the detection and targeting of cancer cells. In this work, we report a novel and facile approach to synthesize Au/Fe 3 O 4 @C JNPs, which were further selectively functionalized with amino-poly(ethylene glycol)thiol (NH 2 -PEG-SH) and folic acid (FA) on the exposed Au domains to achieve high contrast for X-ray computed tomography (CT) imaging, excellent stability, good biocompatibility, as well as cancer cell-specific targeting. Meanwhile, the other Fe 3 O 4 @C sides with mesoporous structure served as a drug delivery vehicle for doxorubicin (DOX), an efficient photothermal therapy (PTT) agent, and a magnetic resonance (MR) imaging contrast agent. Taking these features together, these unique multifunctional JNPs provide an intriguing nanoplatform for dual-modal CT and MR imaging-guided actively targeted chemo-photothermal synergistic cancer therapy. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Feasibility of CBCT-based target and normal structure delineation in prostate cancer radiotherapy: Multi-observer and image multi-modality study

    International Nuclear Information System (INIS)

    Luetgendorf-Caucig, Carola; Fotina, Irina; Stock, Markus; Poetter, Richard; Goldner, Gregor; Georg, Dietmar

    2011-01-01

    Background and purpose: In-room cone-beam CT (CBCT) imaging and adaptive treatment strategies are promising methods to decrease target volumes and to spare organs at risk. The aim of this work was to analyze the inter-observer contouring uncertainties of target volumes and organs at risks (oars) in localized prostate cancer radiotherapy using CBCT images. Furthermore, CBCT contouring was benchmarked against other image modalities (CT, MR) and the influence of subjective image quality perception on inter-observer variability was assessed. Methods and materials: Eight prostate cancer patients were selected. Seven radiation oncologists contoured target volumes and oars on CT, MRI and CBCT. Volumes, coefficient of variation (COV), conformity index (cigen), and coordinates of center-of-mass (COM) were calculated for each patient and image modality. Reliability analysis was performed for the support of the reported findings. Subjective perception of image quality was assessed via a ten-scored visual analog scale (VAS). Results: The median volume for prostate was larger on CT compared to MRI and CBCT images. The inter-observer variation for prostate was larger on CBCT (CIgen = 0.57 ± 0.09, 0.61 reliability) compared to CT (CIgen = 0.72 ± 0.07, 0.83 reliability) and MRI (CIgen = 0.66 ± 0.12, 0.87 reliability). On all image modalities values of the intra-observer reliability coefficient (0.97 for CT, 0.99 for MR and 0.94 for CBCT) indicated high reproducibility of results. For all patients the root mean square (RMS) of the inter-observer standard deviation (σ) of the COM was largest on CBCT with σ(x) = 0.4 mm, σ(y) = 1.1 mm, and σ(z) = 1.7 mm. The concordance in delineating OARs was much stronger than for target volumes, with average CIgen > 0.70 for rectum and CIgen > 0.80 for bladder. Positive correlations between CIgen and VAS score of the image quality were observed for the prostate, seminal vesicles and rectum. Conclusions: Inter-observer variability for target

  11. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    Science.gov (United States)

    2008-03-01

    BMTP-11 and BMTP-78. We have two GMP grade drugs geared for IND filing with the FDA. They are targeted to the interleukin 11 receptor (IL-11R) and...Adults Acquiring Lung Cancer Knowledge (P young adults tobacco use remains a major public health problem in spite of the rec in factors of smoking...initiation among ad onsiderable volume of literature is currently avac designing tobacco prevention and cessation among youth. Focusing on this major

  12. The planning target volume margins detected by cone-beam CT in head and neck cancer patients treated by image-guided intensity modulated radiotherapy

    International Nuclear Information System (INIS)

    Liu Jun; Chen Hong; Zhang Guoqiao; Chen Fei; Zhang Li

    2011-01-01

    Objective: To determine the planning target volume margins of head and neck cancers treated by image guided radiotherapy (IGRT). Methods: 464 sets cone beam computed tomography (CBCT) images before setup correction and 126 sets CBCT images after correction were obtained from 51 head and neck cancer patients treated by IGRT in our department. The systematic and random errors were evaluated by either online or offline correction through registering the CBCT images to the planning CT. The data was divided into 3 groups according to the online correction times. Results: The isocenter shift were 0.37 mm ± 2.37 mm, -0.43 mm ± 2.30 mm and 0.47 mm ± 2.65 mm in right-left (RL), anterior-posterior (AP) and superior-inferior (SI) directions respectively before correction, and it reduced to 0.08 mm ± 0.68 mm, -0.03 mm ± 0.74 mm and 0.03 mm ± 0.80 mm when evaluated by 126 sets corrected CBCT images. The planning target volume (PTV) margin from clinical target volume (CTV) before correction were: 6.41 mm, 6.15 mm and 7.10 mm based on two parameter model, and it reduced to 1.78 mm, 1.80 mm and 1.97 mm after correction. The PTV margins were 3.8 mm, 3.8 mm, 4.0 mm; 4.0 mm, 4.0 mm, 5.0 mm and 5.4 mm, 5.2 mm, 6.1 mm in RL, AP and SI respectively when online-correction times were more than 15 times, 11-15 times, 5-10 times. Conclusions: CBCT-based on online correction reduce the PTV margin for head and neck cancers treated by IGRT and ensure more precise dose delivery and less normal tissue complications. (authors)

  13. Integrin-Targeted Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography for Imaging Tumor Progression and Early Response in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Ma, Xiaopeng; Phi Van, Valerie; Kimm, Melanie A; Prakash, Jaya; Kessler, Horst; Kosanke, Katja; Feuchtinger, Annette; Aichler, Michaela; Gupta, Aayush; Rummeny, Ernst J; Eisenblätter, Michel; Siveke, Jens; Walch, Axel K; Braren, Rickmer; Ntziachristos, Vasilis; Wildgruber, Moritz

    2017-01-01

    Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT) for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC) model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF) probe. ανβ3-targeted FMT-XCT was able to track tumor progression. Cilengitide was able to substantially block the binding of the NIRF probe and suppress the imaging signal. Additionally mice were treated with an established chemotherapy regimen of Cisplatin and Bevacizumab or with a novel MEK inhibitor (Refametinib) for 2 weeks. While μCT revealed only a moderate slowdown of tumor growth, ανβ3 dependent signal decreased significantly compared to non-treated mice already at one week post treatment. ανβ3 targeted imaging might therefore become a promising tool for assessment of early therapy response in the future. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. SU-F-J-34: Automatic Target-Based Patient Positioning Framework for Image-Guided Radiotherapy in Prostate Cancer Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Sasahara, M; Arimura, H; Hirose, T; Ohga, S; Honda, H; Sasaki, T [Kyushu University, Fukuoka (Japan); Shibayama, Y; Umezu, Y [Kyushu University Hospital, Fukuoka (Japan)

    2016-06-15

    Purpose: Current image-guided radiotherapy (IGRT) procedure is bonebased patient positioning, followed by subjective manual correction using cone beam computed tomography (CBCT). This procedure might cause the misalignment of the patient positioning. Automatic target-based patient positioning systems achieve the better reproducibility of patient setup. Our aim of this study was to develop an automatic target-based patient positioning framework for IGRT with CBCT images in prostate cancer treatment. Methods: Seventy-three CBCT images of 10 patients and 24 planning CT images with digital imaging and communications in medicine for radiotherapy (DICOM-RT) structures were used for this study. Our proposed framework started from the generation of probabilistic atlases of bone and prostate from 24 planning CT images and prostate contours, which were made in the treatment planning. Next, the gray-scale histograms of CBCT values within CTV regions in the planning CT images were obtained as the occurrence probability of the CBCT values. Then, CBCT images were registered to the atlases using a rigid registration with mutual information. Finally, prostate regions were estimated by applying the Bayesian inference to CBCT images with the probabilistic atlases and CBCT value occurrence probability. The proposed framework was evaluated by calculating the Euclidean distance of errors between two centroids of prostate regions determined by our method and ground truths of manual delineations by a radiation oncologist and a medical physicist on CBCT images for 10 patients. Results: The average Euclidean distance between the centroids of extracted prostate regions determined by our proposed method and ground truths was 4.4 mm. The average errors for each direction were 1.8 mm in anteroposterior direction, 0.6 mm in lateral direction and 2.1 mm in craniocaudal direction. Conclusion: Our proposed framework based on probabilistic atlases and Bayesian inference might be feasible to

  15. Quantitative PET Imaging with Novel HER3-Targeted Peptides Selected by Phage Display to Predict Androgen-Independent Prostate Cancer Progression

    Science.gov (United States)

    2017-12-01

    demonstrated high levels of HER3 in the prostate cancer and not in the breast cancer, consistent with PET imaging (Figure 4B-C). In fact , when the PET...feedback on my research with established prostate cancer specific and imaging specific scientists in my field. I have accomplished this through...research on imaging HER3 in prostate cancer by molecular imaging scientists . Impact on Technology Transfer The technology developed by this grant has led

  16. Early experience with multiparametric magnetic resonance imaging-targeted biopsies under visual transrectal ultrasound guidance in patients suspicious for prostate cancer undergoing repeated biopsy

    DEFF Research Database (Denmark)

    Boesen, Lars; Noergaard, Nis; Chabanova, Elizaveta

    2015-01-01

    OBJECTIVES: The purpose of this study was to investigate the detection rate of prostate cancer (PCa) by multiparametric magnetic resonance imaging-targeted biopsies (mp-MRI-bx) in patients with prior negative transrectal ultrasound biopsy (TRUS-bx) sessions without previous experience of this...... in all 39 patients. Both PI-RADS and Likert scoring showed a high correlation between suspicion of malignancy and biopsy results (p cancer detected only on mp-MRI-bx outside the TRUS-bx areas (p = 0.025) and another seven patients (21%) had an overall Gleason score...... upgrade of at least one grade based on the mp-MRI-bx. Secondary PCa lesions not visible on mp-MRI were detected by TRUS-bx in six out of 39 PCa patients. The secondary foci were all Gleason 6 (3 + 3) in 5-10% of the biopsy core. According to the Epstein criteria, 37 out of 39 cancer patients were...

  17. In vivo targeted magnetic resonance imaging and visualized photodynamic therapy in deep-tissue cancers using folic acid-functionalized superparamagnetic-upconversion nanocomposites

    Science.gov (United States)

    Zeng, Leyong; Luo, Lijia; Pan, Yuanwei; Luo, Song; Lu, Guangming; Wu, Aiguo

    2015-05-01

    Multifunctional nanoprobes used in magnetic resonance imaging (MRI) and photodynamic therapy (PDT) also have potential applications in diagnosis and visualized therapy of cancers, and hence it is important to investigate the active-targeting ability and in vivo reliability of these nanoprobes. In this work, folic acid (FA)-targeted, photosensitizer (PS)-loaded Fe3O4@NaYF4:Yb/Er (FA-NPs-PS) nanocomposites were synthesized for in vivo T2-weighted MRI and visualized PDT of cancers by modeling MCF-7 tumor-bearing nude mice. By measuring the upconversion luminescence (UCL) and fluorescence emission spectra, the as-prepared FA-NPs-PS nanocomposites showed near-infrared (NIR)-triggered PDT performance due to the production of a singlet oxygen species. Moreover, by tracing PS fluorescence in MCF-7, HeLa cells and in MCF-7 tumors, the FA-targeted nanocomposites demonstrated good targeting ability both in vitro and in vivo. Under the irradiation of a 980 nm laser, the viabilities of MCF-7 and HeLa cells incubated with FA-NPs-PS nanocomposites could decrease to about 18.4% and 30.7%, respectively, and the inhibition of MCF-7 tumors could reach about 94.9%. The transverse MR relaxivity of 63.79 mM-1 s-1 (r2 value) and in vivo MR imaging of MCF-7 tumors indicated an excellent T2-weighted MR performance. This work demonstrated that FA-targeted MRI/PDT nanoprobes are effective for in vivo diagnosis and visualized therapy of breast cancers.Multifunctional nanoprobes used in magnetic resonance imaging (MRI) and photodynamic therapy (PDT) also have potential applications in diagnosis and visualized therapy of cancers, and hence it is important to investigate the active-targeting ability and in vivo reliability of these nanoprobes. In this work, folic acid (FA)-targeted, photosensitizer (PS)-loaded Fe3O4@NaYF4:Yb/Er (FA-NPs-PS) nanocomposites were synthesized for in vivo T2-weighted MRI and visualized PDT of cancers by modeling MCF-7 tumor-bearing nude mice. By measuring the

  18. uPAR-targeted optical near-infrared (NIR) fluorescence imaging and PET for image-guided surgery in head and neck cancer

    DEFF Research Database (Denmark)

    Christensen, Anders; Juhl, Karina; Persson, Morten

    2017-01-01

    the feasibility of combining two uPARtargeted probes in a preclinical head and neck cancer model. The PET modality provided preoperative non-invasive tumor imaging and the optical modality allowed for real-time fluorescence-guided tumor detection and resection. Clinical translation of this platform seems...

  19. Targeted Cancer Therapies

    Science.gov (United States)

    ... some cancers, the malignant cells are stimulated to divide continuously without being prompted to do so by ... use this content on your website or other digital platform? Our syndication services page shows you how. ...

  20. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...

  1. Cancer Stratification by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Justus Weber

    2015-03-01

    Full Text Available The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2. Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter, as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers.

  2. Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    Science.gov (United States)

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Adur, Malavika K; Utterback, Chet W; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-01-01

    Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

  3. Interleukin 16- (IL-16- Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Animesh Barua

    2015-01-01

    Full Text Available Limited resolution of transvaginal ultrasound (TVUS scanning is a significant barrier to early detection of ovarian cancer (OVCA. Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16 by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P<0.05 and late stages (P<0.001. Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

  4. Functionalized polymeric nanoparticles loaded with indocyanine green as theranostic materials for targeted molecular near infrared fluorescence imaging and photothermal destruction of ovarian cancer cells.

    Science.gov (United States)

    Bahmani, Baharak; Guerrero, Yadir; Bacon, Danielle; Kundra, Vikas; Vullev, Valentine I; Anvari, Bahman

    2014-09-01

    Ovarian cancer remains the deadliest malignancy of the female reproductive system. The ability to identify and destroy all ovarian tumor nodules may have a termendous impact on preventing tumor recurrence, and patient survival. The objective of this study is to investigate the effectiveness of a nano-structured system for combined near infrared (NIR) fluorescence imaging of human epidermal growth factor receptor-2 (HER2) over-expression, as a biomarker of ovarian cancer cells, and photothermal destruction of these cells in vitro. The nano-structured system consists of the near infrared dye, indocyanine green (ICG), encapsulated within poly(allylamine) hydrochloride chains cross-linked ionically with sodium phosphate. The surface of the construct is functionalized by covalently attached polyethylene glycol, and monoclonal antibodies against HER2 using reducitve amination methods. We use dynamic light scattering, and absorption and fluorescence spectroscopy for phyiscal characterization of the constructs. Flow cytometry and fluorescence microscopy are used to investigate molecular targeting and imaging capabilities of the constructs against SKOV3 and OVCAR3 ovarian cancer cell lines, which have relatively high and low expression levels of the HER2 receptor, respectively. Continuous NIR laser irradiation at 808 nm is used to investigating the utility of the constructs in mediating photothermal destruction of SKOV3 cells. Flow cytometry results indicate that the functionalized nano-constructs are more effective in targeting the HER2 receptor than non-encapsulated ICG and non-functionlaized constructs (P functionalized constructs in NIR imaging of HER2 overexpression. The functionalized nano-constructs are also capable of inducing a significantly greater increase in photothermal destruction of SKOV3 cells than free ICG and non-functionalized constructs (P functionalized with the monoclonal antibodies, as thernaostic materials for targted molecular NIR imaging of

  5. Tumor Targeting via Sialic Acid: [68Ga]DOTA-en-pba as a New Tool for Molecular Imaging of Cancer with PET.

    Science.gov (United States)

    Tsoukalas, Charalambos; Geninatti-Crich, Simonetta; Gaitanis, Anastasios; Tsotakos, Theodoros; Paravatou-Petsotas, Maria; Aime, Silvio; Jiménez-Juárez, Rogelio; Anagnostopoulos, Constantinos D; Djanashvili, Kristina; Bouziotis, Penelope

    2018-02-20

    The aim of this study was to demonstrate the potential of Ga-68-labeled macrocycle (DOTA-en-pba) conjugated with phenylboronic vector for tumor recognition by positron emission tomography (PET), based on targeting of the overexpressed sialic acid (Sia). The imaging reporter DOTA-en-pba was synthesized and labeled with Ga-68 at high efficiency. Cell binding assay on Mel-C and B16-F10 melanoma cells was used to evaluate melanin production and Sia overexpression to determine the best model for demonstrating the capability of [ 68 Ga]DOTA-en-pba to recognize tumors. The in vivo PET imaging was done with B16-F10 tumor-bearing SCID mice injected with [ 68 Ga]DOTA-en-pba intravenously. Tumor, blood, and urine metabolites were assessed to evaluate the presence of a targeting agent. The affinity of [ 68 Ga]DOTA-en-pba to Sia was demonstrated on B16-F10 melanoma cells, after the production of melanin as well as Sia overexpression was proved to be up to four times higher in this cell line compared to that in Mel-C cells. Biodistribution studies in B16-F10 tumor-bearing SCID mice showed blood clearance at the time points studied, while uptake in the tumor peaked at 60 min post-injection (6.36 ± 2.41 % ID/g). The acquired PET images were in accordance with the ex vivo biodistribution results. Metabolite assessment on tumor, blood, and urine samples showed that [ 68 Ga]DOTA-en-pba remains unmetabolized up to at least 60 min post-injection. Our work is the first attempt for in vivo imaging of cancer by targeting overexpression of sialic acid on cancer cells with a radiotracer in PET.

  6. Targeted Therapies in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Selen Dogan

    2014-04-01

    Full Text Available Endometrial cancer is the most common genital cancer in developed world. It is generally diagnosed in early stage and it has a favorable prognosis. However, advanced staged disease and recurrences are difficult to manage. There are some common genetic alterations related to endometrial carcinogenesis in similar fashion to other cancers. Personalized medicine, which means selection of best suited treatment for an individual, has gain attention in clinical care of patients in recent years. Targeted therapies were developed as a part of personalized or %u201Ctailored%u201D medicine and specifically acts on a target or biologic pathway. There are quite a number of molecular alteration points in endometrial cancer such as PTEN tumor suppressor genes, DNA mismatch repair genes, PI3K/AKT/mTOR pathway and p53 oncogene which all might be potential candidates for tailored targeted therapy. In recent years targeted therapies has clinical application in ovarian cancer patients and in near future with the advent of new agents these %u201Ctailored%u201D drugs will be in market for routine clinical practice in endometrial cancer patients, in primary disease and recurrences as well.

  7. Synthesis and characterization of Her2-NLP peptide conjugates targeting circulating breast cancer cells: cellular uptake and localization by fluorescent microscopic imaging.

    Science.gov (United States)

    Cai, Huawei; Singh, Ajay N; Sun, Xiankai; Peng, Fangyu

    2015-01-01

    To synthesize a fluorescent Her2-NLP peptide conjugate consisting of Her2/neu targeting peptide and nuclear localization sequence peptide (NLP) and assess its cellular uptake and intracellular localization for radionuclide cancer therapy targeting Her2/neu-positive circulating breast cancer cells (CBCC). Fluorescent Cy5.5 Her2-NLP peptide conjugate was synthesized by coupling a bivalent peptide sequence, which consisted of a Her2-binding peptide (NH2-GSGKCCYSL) and an NLP peptide (CGYGPKKKRKVGG) linked by a polyethylene glycol (PEG) chain with 6 repeating units, with an activated Cy5.5 ester. The conjugate was separated and purified by HPLC and then characterized by Maldi-MS. The intracellular localization of fluorescent Cy5.5 Her2-NLP peptide conjugate was assessed by fluorescent microscopic imaging using a confocal microscope after incubation of Cy5.5-Her2-NLP with Her2/neu positive breast cancer cells and Her2/neu negative control breast cancer cells, respectively. Fluorescent signals were detected in cytoplasm of Her2/neu positive breast cancer cells (SKBR-3 and BT474 cell lines), but not or little in cytoplasm of Her2/neu negative breast cancer cells (MDA-MB-231), after incubation of the breast cancer cells with Cy5.5-Her2-NLP conjugates in vitro. No fluorescent signals were detected within the nuclei of Her2/neu positive SKBR-3 and BT474 breast cancer cells, neither Her2/neu negative MDA-MB-231 cells, incubated with the Cy5.5-Her2-NLP peptide conjugates, suggesting poor nuclear localization of the Cy5.5-Her2-NLP conjugates localized within the cytoplasm after their cellular uptake and internalization by the Her2/neu positive breast cancer cells. Her2-binding peptide (KCCYSL) is a promising agent for radionuclide therapy of Her2/neu positive breast cancer using a β(-) or α emitting radionuclide, but poor nuclear localization of the Her2-NLP peptide conjugates may limit its use for eradication of Her2/neu-positive CBCC using I-125 or other Auger electron

  8. Paclitaxel-loaded and A10-3.2 aptamer-targeted poly(lactide-co-glycolic acid nanobubbles for ultrasound imaging and therapy of prostate cancer

    Directory of Open Access Journals (Sweden)

    Wu M

    2017-07-01

    Full Text Available Meng Wu,1,2 Ying Wang,3 Yiru Wang,2 Mingbo Zhang,2 Yukun Luo,2 Jie Tang,2 Zhigang Wang,4 Dong Wang,5 Lan Hao,4 Zhibiao Wang6 1School of Medicine, Nankai University, Tianjin, 2Department of Ultrasound, Chinese PLA General Hospital, Beijing, 3Wuhan Textile University, Wuhan, 4Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, 5Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, 6College of Biomedical Engineering, Chongqing Medical University, Chongqing, People’s Republic of China Abstract: In the current study, we synthesized prostate cancer-targeting poly(lactide-co-glycolic acid (PLGA nanobubbles (NBs modified using A10-3.2 aptamers targeted to prostate-specific membrane antigen (PSMA and encapsulated paclitaxel (PTX. We also investigated their impact on ultrasound (US imaging and therapy of prostate cancer. PTX-A10-3.2-PLGA NBs were developed using water-in-oil-in-water (water/oil/water double emulsion and carbodiimide chemistry approaches. Fluorescence imaging together with flow cytometry verified that the PTX-A10-3.2-PLGA NBs were successfully fabricated and could specifically bond to PSMA-positive LNCaP cells. We speculated that, in vivo, the PTX-A10-3.2-PLGA NBs would travel for a long time, efficiently aim at prostate cancer cells, and sustainably release the loaded PTX due to the improved permeability together with the retention impact and US-triggered drug delivery. The results demonstrated that the combination of PTX-A10-3.2-PLGA NBs with low-frequency US achieved high drug release, a low 50% inhibition concentration, and significant cell apoptosis in vitro. For mouse prostate tumor xenografts, the use of PTX-A10-3.2-PLGA NBs along with low-frequency US achieved the highest tumor inhibition rate, prolonging the survival of tumor-bearing nude mice without obvious systemic toxicity. Moreover, LNCaP xenografts in mice were utilized

  9. Design, Synthesis, and Characterization of Folate-Targeted Platinum-Loaded Theranostic Nanoemulsions for Therapy and Imaging of Ovarian Cancer.

    Science.gov (United States)

    Patel, Niravkumar R; Piroyan, Aleksandr; Nack, Abbegial H; Galati, Corin A; McHugh, Mackenzi; Orosz, Samantha; Keeler, Amanda W; O'Neal, Sara; Zamboni, William C; Davis, Barbara; Coleman, Timothy P

    2016-06-06

    Platinum (Pt) based chemotherapy is widely used to treat many types of cancer. Pt therapy faces challenges such as dose limiting toxicities, cumulative side effects, and multidrug resistance. Nanoemulsions (NEs) have tremendous potential in overcoming these challenges as they can be designed to improve circulation time, limit non-disease tissue uptake, and enhance tumor uptake by surface modification. We designed novel synthesis of three difattyacid platins, dimyrisplatin, dipalmiplatin, and distearyplatin, suitable for encapsulation in the oil core of an NE. The dimyrisplatin, dipalmiplatin, and distearyplatin were synthesized, characterized, and loaded into the oil core of our NEs, NMI-350, NMI-351, and NMI-352 respectively. Sequestration of the difattyacid platins was accomplished through high energy microfluidization. To target the NE, FA-PEG3400-DSPE was incorporated into the surface during microfluidization. The FA-NEs selectively bind the folate receptor α (FR-α) and utilize receptor mediated endocytosis to deliver Pt past cell surface resistance mechanisms. FR-α is overexpressed in a number of oncological conditions including ovarian cancer. The difattyacid platins, lipidated Gd-DTPA, and lipidated folate were characterized by nuclear magnetic resonance (NMR), mass spectrometry (MS), and elemental analysis. NEs were synthesized using high shear microfluidization process and characterized for size, zeta-potential, and loading efficiency. In vitro cytotoxicity was determined using KB-WT (Pt-sensitive) and KBCR-1000 (Pt-resistant) cancer cells and measured by MTT assay. Pharmacokinetic profiles were studied in CD-1 mice. NEs loaded with difattyacid platins are highly stable and had size distribution in the range of ∼120 to 150 nm with low PDI. Cytotoxicity data indicates the longer the fatty acid chains, the less potent the NEs. The inclusion of C6-ceramide, an apoptosis enhancer, and surface functionalization with folate molecules significantly increased

  10. In vivo photoacoustic imaging of cancer using indocyanine green-labeled monoclonal antibody targeting the epidermal growth factor receptor.

    Science.gov (United States)

    Sano, Kohei; Ohashi, Manami; Kanazaki, Kengo; Ding, Ning; Deguchi, Jun; Kanada, Yuko; Ono, Masahiro; Saji, Hideo

    2015-08-28

    Photoacoustic (PA) imaging is an attractive imaging modality for sensitive and depth imaging of biomolecules with high resolution in vivo. The aim of this study was to evaluate the effectiveness of an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (panitumumab; Pan) labeled with indocyanine green derivative (ICG-EG4-Sulfo-OSu), Pan-EG4-ICG, as a PA imaging probe to target cancer-associated EGFR. In vitro PA imaging studies demonstrated that Pan-EG4-ICG yielded high EGFR-specific PA signals in EGFR-positive cells. To determine the optimal injection dose and scan timing, we investigated the biodistribution of radiolabeled Pan-EG4-ICG (200-400 μg) in A431 tumor (EGFR++)-bearing mice. The highest tumor accumulation (29.4% injected dose/g) and high tumor-to-blood ratio (2.1) was observed 7 days after injection of Pan-EG4-ICG (400 μg). In in vivo PA imaging studies using Pan-EG4-ICG (400 μg), the increase in PA signal (114%) was observed in A431 tumors inoculated in the mammary glands 7 days post-injection. Co-injection of excess Pan resulted in a 35% inhibition of this PA signal, indicating the EGFR-specific accumulation. In conclusion, the ICG-labeled monoclonal antibody (i.e., panitumumab) has the potential to enhance target-specific PA signal, leading to the discrimination of aggressiveness and metastatic potential of tumors and the selection of effective therapeutic strategies. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Imaging in oral cancers

    Directory of Open Access Journals (Sweden)

    Supreeta Arya

    2012-01-01

    Full Text Available Oral cavity squamous cell cancers form a significant percentage of the cancers seen in India. While clinical examination allows direct visualization, it cannot evaluate deep extension of disease. Cross-sectional imaging has become the cornerstone in the pretreatment evaluation of these cancers and provides accurate information about the extent and depth of disease that can help decide the appropriate management strategy and indicate prognosis. Early cancers are treated with a single modality, either surgery or radiotherapy while advanced cancers are offered a combination of surgery, radiotherapy and chemotherapy. Imaging can decide resectability, help plan the precise extent of resection, and indicate whether organ conservation therapy should be offered. Quality of life issues necessitate preservation of form and function and pretreatment imaging helps plan appropriate reconstruction and counsel patients regarding lifestyle changes. Oral cavity has several subsites and the focus of the review is squamous cancers of the gingivobuccal region, oral tongue and retromolar trigone as these are most frequently encountered in the subcontinent. References for this review were identified by searching Medline and PubMed databases. Only articles published in English language literature were selected. This review aims to familiarize the radiologist with the relevant anatomy of the oral cavity, discuss the specific issues that influence prognosis and management at the above subsites, the optimal imaging methods, the role of imaging in accurately staging these cancers and in influencing management. A checklist for reporting will emphasize the information to be conveyed by the radiologist.

  12. A Novel ¹¹¹In-Labeled Anti-Prostate-Specific Membrane Antigen Nanobody for Targeted SPECT/CT Imaging of Prostate Cancer.

    Science.gov (United States)

    Chatalic, Kristell L S; Veldhoven-Zweistra, Joke; Bolkestein, Michiel; Hoeben, Sander; Koning, Gerben A; Boerman, Otto C; de Jong, Marion; van Weerden, Wytske M

    2015-07-01

    Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer (PCa) and a promising target for molecular imaging and therapy. Nanobodies (single-domain antibodies, VHH) are the smallest antibody-based fragments possessing ideal molecular imaging properties, such as high target specificity and rapid background clearance. We developed a novel anti-PSMA Nanobody (JVZ-007) for targeted imaging and therapy of PCa. Here, we report on the application of the (111)In-radiolabeled Nanobody for SPECT/CT imaging of PCa. A Nanobody library was generated by immunization of a llama with 4 human PCa cell lines. Anti-PSMA Nanobodies were captured by biopanning on PSMA-overexpressing cells. JVZ-007 was selected for evaluation as an imaging probe. JVZ-007 was initially produced with a c-myc-hexahistidine (his) tag allowing purification and detection. The c-myc-his tag was subsequently replaced by a single cysteine at the C terminus, allowing site-specific conjugation of chelates for radiolabeling. JVZ-007-c-myc-his was conjugated to 2-(4-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (p-SCN-DTPA) via the lysines, whereas JVZ-007-cys was conjugated to maleimide-DTPA via the C-terminal cysteine. PSMA targeting was analyzed in vitro by cell-binding experiments using flow cytometry, autoradiography, and internalization assays with various PCa cell lines and patient-derived xenografts (PDXs). The targeting properties of radiolabeled Nanobodies were evaluated in vivo in biodistribution and SPECT/CT imaging experiments, using nude mice bearing PSMA-positive PC-310 and PSMA-negative PC-3 tumors. JVZ-007 was successfully conjugated to DTPA for radiolabeling with (111)In at room temperature. (111)In-JVZ007-c-myc-his and (111)In-JVZ007-cys internalized in LNCaP cells and bound to PSMA-expressing PDXs and, importantly, not to PSMA-negative PDXs and human kidneys. Good tumor targeting and fast blood clearance were observed for (111)In-JVZ-007-c-myc-his and (111)In

  13. Comparison of measurements of the uterus and cervix obtained by magnetic resonance and transabdominal ultrasound imaging to identify the brachytherapy target in patients with cervix cancer.

    Science.gov (United States)

    van Dyk, Sylvia; Kondalsamy-Chennakesavan, Srinivas; Schneider, Michal; Bernshaw, David; Narayan, Kailash

    2014-03-15

    To compare measurements of the uterus and cervix obtained with magnetic resonance imaging (MRI) and transabdominal ultrasound to determine whether ultrasound can identify the brachytherapy target and be used to guide conformal brachytherapy planning and treatment for cervix cancer. Consecutive patients undergoing curative treatment with radiation therapy between January 2007 and March 2012 were included in the study. Intrauterine applicators were inserted into the uterine canal while patients were anesthetized. Images were obtained by MRI and transabdominal ultrasound in the longitudinal axis of the uterus with the applicator in treatment position. Measurements were taken at the anterior and posterior surface of the uterus at 2.0-cm intervals along the applicator, from the external os to the tip of the applicator. Data were analyzed using Bland Altman plots examining bias and 95% limits of agreement. A total of 192 patients contributed 1668 measurements of the cervix and uterus. Mean (± SD) differences of measurements between imaging modalities at the anterior and posterior uterine surface ranged from 1.5 (± 3.353) mm to 3.7 (± 3.856) mm, and -1.46 (± 3.308) mm to 0.47 (± 3.502) mm, respectively. The mean differences were less than 3 mm in the cervix. The mean differences were less than 1.5 mm at all measurement points on the posterior surface. Differences in the measurements of the cervix and uterus obtained by MRI and ultrasound were within clinically acceptable limits. Transabdominal ultrasound can be substituted for MRI in defining the target volume for conformal brachytherapy treatment of cervix cancer. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  14. Comparison of Measurements of the Uterus and Cervix Obtained by Magnetic Resonance and Transabdominal Ultrasound Imaging to Identify the Brachytherapy Target in Patients With Cervix Cancer

    International Nuclear Information System (INIS)

    Dyk, Sylvia van; Kondalsamy-Chennakesavan, Srinivas; Schneider, Michal; Bernshaw, David; Narayan, Kailash

    2014-01-01

    Purpose: To compare measurements of the uterus and cervix obtained with magnetic resonance imaging (MRI) and transabdominal ultrasound to determine whether ultrasound can identify the brachytherapy target and be used to guide conformal brachytherapy planning and treatment for cervix cancer. Methods and Materials: Consecutive patients undergoing curative treatment with radiation therapy between January 2007 and March 2012 were included in the study. Intrauterine applicators were inserted into the uterine canal while patients were anesthetized. Images were obtained by MRI and transabdominal ultrasound in the longitudinal axis of the uterus with the applicator in treatment position. Measurements were taken at the anterior and posterior surface of the uterus at 2.0-cm intervals along the applicator, from the external os to the tip of the applicator. Data were analyzed using Bland Altman plots examining bias and 95% limits of agreement. Results: A total of 192 patients contributed 1668 measurements of the cervix and uterus. Mean (±SD) differences of measurements between imaging modalities at the anterior and posterior uterine surface ranged from 1.5 (±3.353) mm to 3.7 (±3.856) mm, and −1.46 (±3.308) mm to 0.47 (±3.502) mm, respectively. The mean differences were less than 3 mm in the cervix. The mean differences were less than 1.5 mm at all measurement points on the posterior surface. Conclusion: Differences in the measurements of the cervix and uterus obtained by MRI and ultrasound were within clinically acceptable limits. Transabdominal ultrasound can be substituted for MRI in defining the target volume for conformal brachytherapy treatment of cervix cancer

  15. Comparison of Measurements of the Uterus and Cervix Obtained by Magnetic Resonance and Transabdominal Ultrasound Imaging to Identify the Brachytherapy Target in Patients With Cervix Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dyk, Sylvia van, E-mail: sylvia.vandyk@petermac.org [Radiation Therapy Services, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Kondalsamy-Chennakesavan, Srinivas [Rural Clinical School, University of Queensland, Toowoomba, Queensland (Australia); Schneider, Michal [Department of Medical Imaging and Radiation Science, Monash University, Clayton, Victoria (Australia); Bernshaw, David [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Narayan, Kailash [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Department of Obstetrics and Gynaecology, Melbourne University, Melbourne, Victoria (Australia)

    2014-03-15

    Purpose: To compare measurements of the uterus and cervix obtained with magnetic resonance imaging (MRI) and transabdominal ultrasound to determine whether ultrasound can identify the brachytherapy target and be used to guide conformal brachytherapy planning and treatment for cervix cancer. Methods and Materials: Consecutive patients undergoing curative treatment with radiation therapy between January 2007 and March 2012 were included in the study. Intrauterine applicators were inserted into the uterine canal while patients were anesthetized. Images were obtained by MRI and transabdominal ultrasound in the longitudinal axis of the uterus with the applicator in treatment position. Measurements were taken at the anterior and posterior surface of the uterus at 2.0-cm intervals along the applicator, from the external os to the tip of the applicator. Data were analyzed using Bland Altman plots examining bias and 95% limits of agreement. Results: A total of 192 patients contributed 1668 measurements of the cervix and uterus. Mean (±SD) differences of measurements between imaging modalities at the anterior and posterior uterine surface ranged from 1.5 (±3.353) mm to 3.7 (±3.856) mm, and −1.46 (±3.308) mm to 0.47 (±3.502) mm, respectively. The mean differences were less than 3 mm in the cervix. The mean differences were less than 1.5 mm at all measurement points on the posterior surface. Conclusion: Differences in the measurements of the cervix and uterus obtained by MRI and ultrasound were within clinically acceptable limits. Transabdominal ultrasound can be substituted for MRI in defining the target volume for conformal brachytherapy treatment of cervix cancer.

  16. Facile synthesis of 5 nm NaYF₄:Yb/Er nanoparticles for targeted upconversion imaging of cancer cells.

    Science.gov (United States)

    Hu, Yueli; Wu, Boyue; Jin, Qing; Wang, Xueyuan; Li, Yan; Sun, Yuxiu; Huo, Jianzhong; Zhao, Xiaojun

    2016-05-15

    5nm intense green emission NaYF4:Yb/Er upconversion nanoparticles (UCNPs) with pure β phase was synthesized with a simple "green" strategy for the first time. Traditional organic solvothermal method is often applied to prepare the high-quality and uniform UCNPs, but the preparation of lanthanide-oleate complexes is laborious as heating and multistep post-treatment for purification are often required. The water-alcohols solvothermal method is environmentally friendly, but the fabricated UCNPs have big size, poor biocompatibility and high cytotoxicity, which limited their application for cell imaging. Herein, NaYF4:Yb/Er UCNPs were prepared with rare-earth nitrates RE(NO3)3 (RE=Y0.80 Yb0.18 Er0.02) as precursors and diethylene glycol (DEG)/ethylene glycol (EG)/water as the solvent. A facile green solvothermal method with the temperature being controlled at 300°C was developed. The as-prepared NaYF4:Yb/Er UCNPs were characterized and were found to have enhanced UC emission and controllable particle size. The as-prepared UCNPs were further functionalized via folic acid coating for the targeted imaging and improved bio- compatibility. It was made the UCNPs potential for upconversion bioimaging of living cells by the strong upconversion luminescence, the excellent biocompatibility, and the super-small size. The good colloidal stability and low cell cytotoxicity of the as-prepared UCNPs and the developed synthesis protocol might advance both the fields of UCNPs and biomolecule-based nanotechnology for future studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Imaging of kidney cancer

    International Nuclear Information System (INIS)

    Guermazi, A.

    2006-01-01

    This is one of the first books to deal specifically with diagnostic imaging of the entire spectrum of kidney cancers. Both new and conventional imaging modalities are fully considered. After an introductory chapter on the histopathological classification of kidney cancers, the advantages and disadvantages of the various imaging modalities used in the diagnosis and assessment of disease extension are documented. Subsequent chapters offer an exhaustive description of the radiological features of the different histological subtypes of kidney cancer, with radiological and histological illustrations and tables. The latest innovations in interventional and minimally invasive procedures are also well covered. The book benefits from carefully chosen and technically excellent images. Each of the 24 chapters is written by an internationally acclaimed expert, making this book the most current and complete treatment of the subject available. It should be of great interest to radiologists, oncologists, and urologists. (orig.)

  18. Characterization and cancer cell targeted imaging properties of human antivascular endothelial growth factor monoclonal antibody conjugated CdTe/ZnS quantum dots.

    Science.gov (United States)

    Pang, Lili; Xu, Jian; Shu, Chang; Guo, Jin; Ma, Xiaona; Liu, Yu; Zhong, Wenying

    2014-12-01

    High luminescence quantum yield water-soluble CdTe/ZnS core/shell quantum dots (QDs) stabilized with thioglycolic acid were synthesized. QDs were chemically coupled to fully humanized antivascular endothelial growth factor165 monoclonal antibodies to produce fluorescent probes. These probes can be used to assay the biological affinity of the antibody. The properties of QDs conjugated to an antibody were characterized by ultraviolet and visible spectrophotometry, fluorescent spectrophotometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transmission electron microscopy and fluorescence microscopy. Cell-targeted imaging was performed in human breast cancer cell lines. The cytotoxicity of bare QDs and fluorescent probes was evaluated in the MCF-7 cells with an MTT viability assay. The results proved that CdTe/ZnS QD-monoclonal antibody nanoprobes had been successfully prepared with excellent spectral properties in target detections. Surface modification by ZnS shell could mitigate the cytotoxicity of cadmium-based QDs. The therapeutic effects of antivascular endothelial growth factor antibodies towards cultured human cancer cells were confirmed by MTT assay. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Non-surgical breast-conservation treatment (KORTUC-BCT) using a new image-guided, enzyme-targeted, and breast cancer stem cell targeted radiosensitization treatment (KORTUC II) for patients with stage I or II breast cancer

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Kubota, Kei; Tadokoro, Michiko

    2012-01-01

    injected into breast tumor tissue twice a week under ultrasound guidance, just prior to each administration of radiation therapy, and we confirmed an even distribution of micro-bubbles of oxygen throughout the target tumor. The injection was started at the 6th fraction of radiation therapy. This injection protocol effectively preserves oxygen concentration in the tumor tissue for more than 24 h following intra-tumoral injection (Tokuhiro S, et al: Oncol Letters 1:1025-1028, 2010). Concerning radiation therapy, hypofraction radiotherapy was given using tangential fields approach and Field-in-field method; energy level was 4MV and the total radiation therapy dose was 44 Gy administered as 2.75 Gy/fraction. An electron boost of 3 Gy was added 3 times just following the 14th, 15th and 16th administrations of 4 MV X-ray irradiation. From a needle biopsy specimen, hormonal status (estrogen and progesterone receptors), HER-2 antigen, and CD44 receptor were examined by immunohistochemistry. Treatment was well tolerated with a minimum of adverse effects in all 39 patients. A total of 36 patients achieved clinically complete response on dynamic MRI study, and the study has not been performed yet for another 3. All of the patients did not show any complications (with the exception of mild dermatitis of Grade I for 24 and Grade II for 15), and cosmetic results were excellent/good for 35 patients. 15 patients under 75 y with stage II breast cancer underwent induction chemotherapy (EC and/or Taxan) prior to the KORTUC II treatment, and 36 patients with estrogen receptor-positive tumors also undertook hormonal therapy following KORTUC II. The mean follow-up period at the end of September 2011 was 30.1 months, at which time all 39 patients were alive without any distant metastases. Only 1 patient had local recurrence, which was discovered at 34 months follow-up. Non-surgical BCT (KORTUC-BCT) can be performed with KORTUC II. KORTUC II has 3 major characteristics: it is image-guided by

  20. Transperineal Magnetic Resonance Imaging-targeted Biopsy versus Transperineal Template Prostate Mapping Biopsy in the Detection of Localised Radio-recurrent Prostate Cancer.

    Science.gov (United States)

    Kanthabalan, A; Abd-Alazeez, M; Arya, M; Allen, C; Freeman, A; Jameson, C; Kirkham, A; Mitra, A V; Payne, H; Punwani, S; Ramachandran, N; Walkden, M; Emberton, M; Ahmed, H U

    2016-09-01

    Multi-parametric magnetic resonance imaging (mpMRI) may identify radio-recurrent intra-prostatic cancer accurately. We aimed to compare visually directed MRI-targeted biopsies (MRI-TB) to an accurate reference standard - transperineal prostate mapping (TPM) biopsies with 5 mm sampling - in the detection of clinically significant cancer in men with biochemical failure after radiotherapy. A retrospective registry analysis between 2006 and 2014 identified 77 men who had undergone mpMRI followed by MRI-TB and TPM. Clinical significance was set at two definitions of disease. Definition 1 was Gleason ≥ 4+3 and/or maximum cancer core length ≥ 6 mm. Definition 2 was Gleason ≥ 3+4 and/or maximum cancer core length ≥ 4 mm. Of the 77 patients included, the mean age was 70 years (range 61-82; standard deviation 5.03). The median prostate-specific antigen (PSA) at the time of external beam radiotherapy (EBRT) was 14 ng/ml (interquartile range 7.83-32.50). The most frequent EBRT dose given was 74 Gy over 37 fractions. Eight patients had iodine-seed implant brachytherapy or high dose rate brachytherapy. Neoadjuvant/adjuvant hormonal therapy use was reported in 38. The time from EBRT to biochemical recurrence was a median of 60 months (interquartile range 36.75-85.00). The median PSA at the time of mpMRI was 4.68 ng/ml (interquartile range 2.68-7.60). The median time between mpMRI and biopsy was 2.76 months (interquartile range 1.58-4.34). In total, 2392 TPM and 381 MRI-TB cores were taken with 18% and 50% cancer detection, respectively. Detection rates of definition 1 clinically significant cancer were 52/77 (68%) versus 55/77 (71%) for MRI-TB and TPM, respectively. MRI-TB was more efficient requiring 1 core versus 2.8 cores to detect definition 2 cancer. MRI-TB seems to have encouraging detection rates for clinically significant cancer with fewer cores compared with TPM, although TPM had higher detection rates for smaller lower grade lesions. Copyright © 2016 The

  1. Targeted deletion of the ara operon of Salmonella typhimurium enhances L-arabinose accumulation and drives PBAD-promoted expression of anti-cancer toxins and imaging agents.

    Science.gov (United States)

    Hong, Hyun; Lim, Daejin; Kim, Geun-Joong; Park, Seung-Hwan; Sik Kim, Hyeon; Hong, Yeongjin; Choy, Hyon E; Min, Jung-Joon

    2014-01-01

    Tumor-specific expression of antitumor drugs can be achieved using attenuated Salmonella typhimurium harboring the PBAD promoter, which is induced by L-arabinose. However, L-arabinose does not accumulate because it is metabolized to D-xylulose-5-P by enzymes encoded by the ara operon in Salmonellae. To address this problem, we developed an engineered strain of S. typhimurium in which the ara operon is deleted. Linear DNA transformation was performed using λ red recombinase to exchange the ara operon with linear DNA carrying an antibiotic-resistance gene with homology to regions adjacent to the ara operon. The ara operon-deleted strain and its parental strain were transformed with a plasmid encoding Renilla luciferase variant 8 (RLuc8) or cytolysin A (clyA) under the control of the PBAD promoter. Luciferase assays demonstrated that RLuc8 expression was 49-fold higher in the ara operon-deleted S. typhimurium than in the parental strain after the addition of L-arabinose. In vivo bioluminescence imaging showed that the tumor tissue targeted by the ara operon-deleted Salmonella had a stronger imaging signal (~30-fold) than that targeted by the parental strain. Mice with murine colon cancer (CT26) that had been injected with the ara operon-deleted S. typhimurium expressing clyA showed significant tumor suppression. The present report demonstrates that deletion of the ara operon of S. typhimurium enhances L-arabinose accumulation and thereby drives PBAD-promoted expression of cytotoxic agents and imaging agents. This is a promising approach for tumor therapy and imaging.

  2. Targeting the Circadian Clock to Treat Cancer

    Science.gov (United States)

    Two compounds that target components of the circadian clock killed several types of cancer cells in the lab and slowed the growth of brain cancer in mice without harming healthy cells, as this Cancer Currents post reports.

  3. Dose-volume analysis of target volume and critical structures in computed tomography image-based multicatheter high-dose-rate interstitial brachytherapy for head and neck cancer

    Directory of Open Access Journals (Sweden)

    Hironori Akiyama

    2017-12-01

    Full Text Available Purpose : To evaluate dose-volume relationships of target volume and critical structures in computed tomography (CT image-based brachytherapy for head and neck cancer. Material and methods : Thirty-seven patients with mobile tongue, floor of mouth, and base of tongue cancer treated with brachytherapy (post-operative alone and as a boost after external beam radiotherapy [EBRT], or definitive alone or as a boost after EBRT were selected. Treatment plans were made using post-implant CT images. The fractionation schedule was 7-15 × 3-5 Gy for post-operative (with or without EBRT, 14-15 × 3 Gy for definitive alone, and 5-10 × 3 Gy for boost treatments. For the target volume, V 100 , D 90 , and dose non-uniformity ratio (DNR were calculated. For the mandible, spinal cord and salivary glands doses to specified volumes were reported. Results : The median values of V 100 and D 90 were 89.9% and 99.9%, respectively; the median values of DNR was 0.46. The median D 2cm 3 of the mandible and spinal cord were 48.3% and 5.8%, respectively. The ipsilateral median D 2cm 3 of parotid and submandibular glands were 6.4% and 12.5%, whereas on the contralateral side, the corresponding values were 5.3% and 7.0%, respectively. Conclusions : Using conformal treatment planning, it was desirable to keep the dose to the mandible, spinal cord, and salivary glands at an acceptable level. The quantitative plan evaluation may help us find correlations between dosimetric parameters and clinical outcome, which may lead to improve the quality of the treatment, but it requires longer follow-up and results from other studies.

  4. Reduced rectal toxicity with ultrasound-based image guided radiotherapy using BAT trademark (B-mode acquisition and targeting system) for prostate cancer

    International Nuclear Information System (INIS)

    Bohrer, Markus; Schroeder, Peter; Welzel, Grit; Wertz, Hansjoerg; Lohr, Frank; Wenz, Frederik; Mai, Sabine Kathrin

    2008-01-01

    To evaluate the effect of image guided radiotherapy with stereotactic ultrasound BAT (B-mode acquisition and targeting system) on rectal toxicity in conformal radiotherapy of prostate cancer. Patients and Methods 42 sequential patients with prostate cancer undergoing radiotherapy before and after the introduction of BAT were included. Planning computed tomography (CT) was performed with empty rectum and moderately filled bladder. The planning target volume (PTV) included the prostate and seminal vesicles with a safety margin of 1.5 cm in anterior and lateral direction. In posterior direction the anterior 1/3 of the rectum circumference were included. Total dose was 66 Gy and a boost of 4 Gy excluding the seminal vesicles. 22 patients (BAT group) were treated with daily stereotactic ultrasound positioning, for the other 20 patients (NoBAT group) an EPID (electronic portal imaging device) was performed once a week. Acute and late genito-urinary (GU) and rectal toxicity and PSA values were evaluated after 1.5, 3, 6, 9 and 12 months. The total median follow up of toxicity was 3 years in the BAT group and 4 years in the NoBAT group. Results In the NoBAT group significant more rectal toxicity occurred, while in GU toxicity no difference was seen. Two patients in the NoBAT group showed late rectal toxicity grade 3, no toxicity > grade 2 occurred in the BAT group. There was no significant difference in PSA reduction between the groups. Conclusion Without BAT significant more acute and a trend to more late rectal toxicity was found. With regard to dose escalation this aspect is currently evaluated with a larger number of patients using intensity-modulated radiotherapy (IMRT). (orig.)

  5. Targeted alpha therapy for cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Barry J [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Raja, Chand [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Rizvi, Syed [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Li Yong [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Tsui, Wendy [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Zhang, David [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Song, Emma [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Qu, C F [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Kearsley, John [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Graham, Peter [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Thompson, John [Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown 2050 NSW (Australia)

    2004-08-21

    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The {sup 213}Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 {mu

  6. Preparation and Evaluation of 99mTc-labeled anti-CD11b Antibody Targeting Inflammatory Microenvironment for Colon Cancer Imaging.

    Science.gov (United States)

    Cheng, Dengfeng; Zou, Weihong; Li, Xiao; Xiu, Yan; Tan, Hui; Shi, Hongcheng; Yang, Xiangdong

    2015-06-01

    CD11b, an active constituent of innate immune response highly expressed in myeloid-derived suppressor cells (MDSCs), can be used as a marker of inflammatory microenvironment, particularly in tumor tissues. In this research, we aimed to fabricate a (99m)Tc-labeled anti-CD11b antibody as a probe for CD11b(+) myeloid cells in colon cancer imaging with single-photon emission computed tomography (SPECT). In situ murine colon tumor model was established in histidine decarboxylase knockout (Hdc(-/-)) mice by chemicals induction. (99m)Tc-labeled anti-CD11b was obtained with labeling yields of over 30% and radiochemical purity of over 95%. Micro-SPECT/CT scans were performed at 6 h post injection to investigate biodistributions and targeting of the probe. In situ colonic neoplasma as small as 3 mm diameters was clearly identified by imaging; after dissection of the animal, anti-CD11b immunofluorescence staining was performed to identify infiltration of CD11b+ MDSCs in microenvironment of colonic neoplasms. In addition, the images displayed intense signal from bone marrow and spleen, which indicated the origin and migration of CD11b(+) MDSCs in vivo, and these results were further proved by flow cytometry analysis. Therefore, (99m)Tc-labeled anti-CD11b SPECT displayed the potential to facilitate the diagnosis of colon tumor in very early stage via detection of inflammatory microenvironment. © 2014 John Wiley & Sons A/S.

  7. Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles

    Directory of Open Access Journals (Sweden)

    Cheng CC

    2013-04-01

    radioisotope indium-111 (111In was measured and analyzed by instant thin layer chromatography. The coupling efficiency of DTPA-conjugated micelles and DTPA/GRP78BP-conjugated micelles with 111In was 85% and 93%, respectively. For characterization and trace imaging, the radioisotope 111In-targeting tumors were detected and imaged in a xenograft murine model using nano single photon emission computed tomography/computed tomography. The results revealed that the radioactive intensity measured in the animals administered with GRP78BP-guided 111In-labeled micelles was statistically higher than that in animals administered with 111In-labeled micelles, demonstrating that GRP78BP more than doubled the accumulation of micelles to the tumor tissue (P < 0.05. The results indicate that the gastric cancer biomarker GRP78 is a probing target in the application of nuclear imaging for tumor diagnosis. This novel GRP78BP-guided micelle agent may be applied in clinical practice to complement the histological diagnosis.Keywords: biomarker, glucose-regulated protein 78, nuclear imaging, gastric cancer, micelles

  8. Transcriptionally targeted gene therapy to detect and treat cancer

    OpenAIRE

    Wu, Lily; Johnson, Mai; Sato, Makoto

    2003-01-01

    The greatest challenge in cancer treatment is to achieve the highest levels of specificity and efficacy. Cancer gene therapy could be designed specifically to express therapeutic genes to induce cancer cell destruction. Cancer-specific promoters are useful tools to accomplish targeted expression; however, high levels of gene expression are needed to achieve therapeutic efficacy. Incorporating an imaging reporter gene in tandem with the therapeutic gene will allow tangible proof of principle t...

  9. Imaging and prostate cancer

    International Nuclear Information System (INIS)

    Schwartz, Lawrence H.

    1996-01-01

    The use of imaging in evaluating patients with prostate cancer is highly dependent upon the purpose of the evaluation. Ultrasound, Computed Tomography, Magnetic Resonance Imaging, TC-99m Bone Scanning, and Positron Emission Tomography may all be utilized for imaging in prostate cancer. The utility of each of these modalities depends upon the intended purpose: for instance, screening, staging, or evaluating for progression of disease in patients with prostate cancer. Transrectal ultrasound is performed by placing a 5MHz to 7.5 MHz transducer in the rectum and imaging the prostate in the coronal and sagittal planes. Prostate cancer generally appears as an area of diminished echogenocity in the peripheral zone of the prostate gland. However, up to 24% of prostate cancers are isoechoic and cannot be well distinguished from the remainder of the peripheral zone. In addition, the incidence of malignancy in a lesion judged to be suspicious on ultrasound is between 20% and 25%. Therefore, while ultrasound is the least expensive of the three cross sectional imaging modalities, its relatively low specificity precludes it from being used as a screening examination. Investigators have also looked at the ability of ultrasound to evaluate the presence and extent of extracapsular spread of prostate cancer. The RDOG (Radiology Diagnostic Oncology Group) multi-institutional cooperative trial reported a disappointing overall accuracy of ultrasound of 58% for staging prostate cancer. The accuracy was somewhat higher 63%, for patients with advanced disease. The other cross-sectional imaging modalities available for imaging the prostate include Computed Tomography and Magnetic Resonance Imaging. Computed Tomography is useful as an 'anatomic' imaging technique to detect lymph node enlargement. It is not sensitive in detecting microscopic nodal involvement with tumor, or tumor in non-enlarged pelvic lymph nodes. The primary prostate neoplasm is generally the same attenuation as the normal

  10. Improved Targeting of Cancers with Nanotherapeutics

    DEFF Research Database (Denmark)

    Foster, Christian; Watson, Andre; Kaplinsky, Joseph John

    2017-01-01

    Targeted cancer nanotherapeutics offers numerous opportunities for the selective uptake of toxic chemotherapies within tumors and cancer cells. The unique properties of nanoparticles, such as their small size, large surface-to-volume ratios, and the ability to achieve multivalency of targeting...... ligands on their surface, provide superior advantages for nanoparticle-based drug delivery to a variety of cancers. This review highlights various key concepts in the design of targeted nanotherapeutics for cancer therapy, and discusses physicochemical parameters affecting nanoparticle targeting, along...... with recent developments for cancer-targeted nanomedicines....

  11. Targeted therapy using nanotechnology: focus on cancer.

    Science.gov (United States)

    Sanna, Vanna; Pala, Nicolino; Sechi, Mario

    2014-01-01

    Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication.

  12. Theranostics Targeting Metastatic Breast Cancer

    Science.gov (United States)

    2017-10-01

    is ideal for optical imaging in vivo. In cell studies on a high-power fluorescent microscope we can see that the targeted dye 3 has a higher...theranostic. Currently we are scaling up the synthesis of this molecule, for photophysical measurements, cellular assays particularly light /dark...absorbs light optimally at a wavelength (around 500 nm) that is too short for efficient penetration of more than a few mm in tis- sue.43,44 To circumvent

  13. 808 nm-excited upconversion nanoprobes with low heating effect for targeted magnetic resonance imaging and high-efficacy photodynamic therapy in HER2-overexpressed breast cancer.

    Science.gov (United States)

    Zeng, Leyong; Pan, Yuanwei; Zou, Ruifen; Zhang, Jinchao; Tian, Ying; Teng, Zhaogang; Wang, Shouju; Ren, Wenzhi; Xiao, Xueshan; Zhang, Jichao; Zhang, Lili; Li, Aiguo; Lu, Guangming; Wu, Aiguo

    2016-10-01

    To avoid the overheating effect of excitation light and improve the efficacy of photodynamic therapy (PDT) of upconversion nanoplatform, a novel nanoprobe based on 808 nm-excited upconversion nanocomposites (T-UCNPs@Ce6@mSiO2) with low heating effect and deep penetration has been successfully constructed for targeted upconversion luminescence, magnetic resonance imaging (MRI) and high-efficacy PDT in HER2-overexpressed breast cancer. In this nanocomposite, photosensitizers (Ce6) were covalently conjugated inside of mesoporous silica to enhance the PDT efficacy by shortening the distance of fluorescence resonance energy transfer and to decrease the cytotoxicity by preventing the undesired leakage of Ce6. Compared with UCNPs@mSiO2@Ce6, UCNPs@Ce6@mSiO2 greatly promoted the singlet oxygen generation and amplified the PDT efficacy under the excitation of 808 nm laser. Importantly, the designed nanoprobe can greatly improve the uptake of HER2-positive cells and tumors by modifying the site-specific peptide, and the in vivo experiments showed excellent MRI and PDT via intravenous injection by modeling MDA-MB-435 tumor-bearing nude mice. Our strategy may provide an effective solution for overcoming the heating effect and improving the PDT efficacy of upconversion nanoprobes, and has potential application in visualized theranostics of HER2-overexpressed breast cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. PSMA-Targeted Nano-Conjugates as Dual-Modality (MRI/PET) Imaging Probes for the Non-Invasive Detection of Prostate Cancer

    National Research Council Canada - National Science Library

    Sun, Xiankai

    2008-01-01

    The goal of this project is to develop dual modality imaging probes for the detection of prostate cancer by doping radioisotopes to iron oxide nanoparticles, so that the sensitivity and specificity...

  15. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2008-01-01

    The projects in this proposal specifically target several signal transduction pathways known to be critical for NSCLC pathogenesis including the EGFR pathway and the more downstream ras/raf/Mek/ERK pathway...

  16. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun Ki; Herbst, Roy

    2006-01-01

    The projects in this proposal specifically target several signal transduction pathways known to be critical for NSCLC pathogenesis including the EGFR pathway and the more downstream ras/raf/Mek/ERK pathway...

  17. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2007-01-01

    The projects in this proposal specifically target several signal transduction pathways known to be critical for NSCLC pathogenesis including the EGFR pathway and the more downstream ras/raf/Mek/ERK pathway...

  18. Novel Targeted Therapies for Inflammatory Breast Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0461 TITLE: Novel Targeted Therapies for Inflammatory Breast Cancer PRINCIPAL INVESTIGATOR: Jose Silva CONTRACTING...CONTRACT NUMBER Novel Targeted Therapies for Inflammatory Breast Cancer 5b. GRANT NUMBER W81XWH-16-1-0461 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) l 5d...NOTES 14. ABSTRACT Inflammatory breast cancer (IBC, ~5% of all breast cancers ) is the most lethal form of breast cancer , presenting a 5- year

  19. Molecular Imaging of Proteases in Cancer

    Directory of Open Access Journals (Sweden)

    Yunan Yang

    2009-01-01

    Full Text Available Proteases play important roles during tumor angiogenesis, invasion, and metastasis. Various molecular imaging techniques have been employed for protease imaging: optical (both fluorescence and bioluminescence, magnetic resonance imaging (MRI, single-photon emission computed tomography (SPECT, and positron emission tomography (PET. In this review, we will summarize the current status of imaging proteases in cancer with these techniques. Optical imaging of proteases, in particular with fluorescence, is the most intensively validated and many of the imaging probes are already commercially available. It is generally agreed that the use of activatable probes is the most accurate and appropriate means for measuring protease activity. Molecular imaging of proteases with other techniques (i.e. MRI, SPECT, and PET has not been well-documented in the literature which certainly deserves much future effort. Optical imaging and molecular MRI of protease activity has very limited potential for clinical investigation. PET/SPECT imaging is suitable for clinical investigation; however the optimal probes for PET/SPECT imaging of proteases in cancer have yet to be developed. Successful development of protease imaging probes with optimal in vivo stability, tumor targeting efficacy, and desirable pharmacokinetics for clinical translation will eventually improve cancer patient management. Not limited to cancer, these protease-targeted imaging probes will also have broad applications in other diseases such as arthritis, atherosclerosis, and myocardial infarction.

  20. Breast cancer imaging devices.

    Science.gov (United States)

    Moadel, Renee M

    2011-05-01

    Conventional mammography is a screening procedure constrained by low specificity in the detection of breast cancer. Approximately 40% of women undergoing mammography screening have dense breast tissue, and conventional mammographic imaging has a sensitivity range of only 50%-85% for malignant lesions. Magnetic resonance imaging (MRI) is now recommended for breast cancer screening in high-risk patients. However, approximately 15% of patients cannot tolerate MRI. These are the clinical situations in which positron emission mammography (PEM) and breast-specific gamma (BSG) camera systems fulfill a need for primary breast cancer imaging. Because breast cancer is the most common malignancy and the second most common cause of cancer death among women, many nuclear medicine imaging techniques are essential in the evaluation and therapy of patients with this disease. Nuclear medicine surgical techniques consist of sentinel lymph node localization and the use of radiolabeled seeds for intraoperative localization of nonpalpable breast cancers. The Food and Drug Administration (FDA) has approved the PEM Flex Solo II scanner, which has the capability for stereotactic biopsy, with an array of pixelated lutetium yttrium orthosilicate (LYSO) crystals, position-sensitive photomultiplier tubes (PS-PMT), and a spatial resolution of 2.4 mm. Clear PEM is a scanner in development with cerium-doped LYSO (LYSO:Ce) crystals, multipixel avalanche photodiodes, depth of interaction measurement with a resolution of 1.3 mm. The Dilon 6800 Gamma Camera is a BSG device approved by the FDA with stereotactic biopsy guidance capability, a pixelated array of sodium iodide crystals, PS-PMTs, and an extrinsic spatial resolution of 6 mm at 3 cm from the camera. GE has just received clearance from the FDA for a molecular breast imaging camera, the Discovery NM 750 b, with pixelated cadmium zinc telluride crystals, semiconductor photoelements and an extrinsic resolution of 3.5 mm at 3 cm. The Society of

  1. Prospects of Targeting the Gastrin Releasing Peptide Receptor and Somatostatin Receptor 2 for Nuclear Imaging and Therapy in Metastatic Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Simone U Dalm

    Full Text Available The gastrin releasing peptide receptor (GRPR and the somatostatin receptor 2 (SSTR2 are overexpressed on primary breast cancer (BC, making them ideal candidates for receptor-mediated nuclear imaging and therapy. The aim of this study was to determine whether these receptors are also suitable targets for metastatic BC.mRNA expression of human BC samples were studied by in vitro autoradiography and associated with radioligand binding. Next, GRPR and SSTR2 mRNA levels of 60 paired primary BCs and metastases from different sites were measured by quantitative reverse transcriptase polymerase chain reaction. Receptor mRNA expression levels were associated with clinico-pathological factors and expression levels of primary tumors and corresponding metastases were compared.Binding of GRPR and SSTR radioligands to tumor tissue correlated significantly with receptor mRNA expression. High GRPR and SSTR2 mRNA levels were associated with estrogen receptor (ESR1-positive tumors (p<0.001 for both receptors. There was no significant difference in GRPR mRNA expression of primary tumors versus paired metastases. Regarding SSTR2 mRNA expression, there was also no significant difference in the majority of cases, apart from liver and ovarian metastases which showed a significantly lower expression compared to the corresponding primary tumors (p = 0.02 and p = 0.03, respectively.Targeting the GRPR and SSTR2 for nuclear imaging and/or treatment has the potential to improve BC care in primary as well as metastatic disease.

  2. Enhanced cellular uptake and phototoxicity of Verteporfin-conjugated gold nanoparticles as theranostic nanocarriers for targeted photodynamic therapy and imaging of cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Linlin [Tianjin Key Laboratory for Photoelectric Materials and Devices, School of Materials Science & Engineering, Tianjin University of Technology, Tianjin 300384 (China); Graduate School of Energy Science and Technology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kim, Tae-Hyun; Kim, Hae-Won [Department of Nanobiomedical Science, Dankook University Graduate School, Cheonan 330-714 (Korea, Republic of); Institute of Tissue Regeneration Engineering (ITREN) & College of Dentistry, Dankook University, Cheonan 330-714 (Korea, Republic of); Ahn, Jin-Chul [Department of Biomedical Science, College of Medicine, Dankook University, Cheonan, 330-714 (Korea, Republic of); Kim, So Yeon, E-mail: kimsy@cnu.ac.kr [Graduate School of Energy Science and Technology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Department of Chemical Engineering Education, College of Education, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

    2016-10-01

    Activatable theranostics with the capacity to respond to a given stimulus have recently been intensively explored to develop more specific, individualized therapies for various diseases, and to combine diagnostic and therapeutic capabilities into a single agent. In this work, we designed tumor-targeting ligand-conjugated block copolymer-gold nanoparticle (AuNP) conjugates as multifunctional nanocarriers of the hydrophobic photosensitizer (PS), verteporfin (Verte), for simultaneous photodynamic therapy and imaging of cancers. Folic acid (FA)-conjugated block copolymers composed of polyethylene glycol (PEG) and poly-β-benzyl-L-aspartate (PBLA) were attached to citrate-stabilized AuNPs through a bidentate dihydrolipoic acid (DHLA) linker. The resulting AuNP conjugates (FA-PEG-P(Asp-Hyd)-DHLA-AuNPs) were significantly more stable than unmodified AuNPs, and their optical properties were not affected by pH. The hydrophobic PS, Verte, was covalently incorporated onto the surfaces of the AuNP conjugates through a pH-sensitive linkage, which increased the water solubility of Verte from < 1 μg/ml to > 2000 μg/ml. The size of FA-PEG-P(Asp-Hyd)-DHLA-AuNPs-Verte as determined by light-scattering measurements was about 110.3 nm, and FE-SEM and FE-TEM images showed that these nanoparticles were spherical and showed adequate dispersivity after modification. In particular, an in vitro cell study revealed high intracellular uptake of FA-PEG-P(Asp-Hyd)-DHLA-AuNPs-Verte (about 98.62%) and marked phototoxicity after laser irradiation compared with free Verte. These results suggest that FA-PEG-P(Asp-Hyd)-DHLA-AuNPs-Verte has great potential as an effective nanocarrier for dual imaging and photodynamic therapy. - Highlights: • We designed theranostic nanocarriers for photodynamic therapy and imaging of cancers. • AuNP conjugates had a spherical shape and a narrow size distribution with a mean diameter of 110.3 nm. • Cellular uptake of free Verte was 18.86%, whereas that of Au

  3. Comparison of internal target volumes defined on 3-dimensional, 4-dimensonal, and cone-beam CT images of non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Li F

    2016-11-01

    Full Text Available Fengxiang Li,1 Jianbin Li,1 Zhifang Ma,1 Yingjie Zhang,1 Jun Xing,1 Huanpeng Qi,1 Dongping Shang21Department of Radiation Oncology, 2Department of Big Bore CT Room, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of ChinaPurpose: The purpose of this study was to compare the positional and volumetric differences of internal target volumes defined on three-dimensional computed tomography (3DCT, four-dimensional CT (4DCT, and cone-beam CT (CBCT images of non-small-cell lung cancer (NSCLC. Materials and methods: Thirty-one patients with NSCLC sequentially underwent 3DCT and 4DCT simulation scans of the thorax during free breathing. The first CBCT was performed and registered to the planning CT using the bony anatomy registration during radiotherapy. The gross tumor volumes were contoured on the basis of 3DCT, maximum intensity projection (MIP of 4DCT, and CBCT. CTV3D (clinical target volume, internal target volumes, ITVMIP and ITVCBCT, were defined with a 7 mm margin accounting for microscopic disease. ITV10 mm and ITV5 mm were defined on the basis of CTV3D: ITV10 mm with a 5 mm margin in left–right (LR, anterior–posterior (AP directions and 10 mm in cranial–caudal (CC direction; ITV5 mm with an isotropic internal margin (IM of 5 mm. The differences in the position, size, Dice’s similarity coefficient (DSC and inclusion relation of different volumes were evaluated.Results: The median size ratios of ITV10 mm, ITV5 mm, and ITVMIP to ITVCBCT were 2.33, 1.88, and 1.03, respectively, for tumors in the upper lobe and 2.13, 1.76, and 1.1, respectively, for tumors in the middle-lower lobe. The median DSCs of ITV10 mm, ITV5 mm, ITVMIP, and ITVCBCT were 0.6, 0.66, and 0.83 for all patients. The median percentages of ITVCBCT not included in ITV10 mm, ITV5 mm, and ITVMIP were 0.1%, 1.63%, and 15.21%, respectively, while the median percentages of ITV10 mm, ITV5 mm

  4. Development of Silicon-Coated Superparamagnetic Iron Oxide Nanoparticles for Targeted Molecular Imaging and Hyperthermic Therapy of Prostate Cancer

    Science.gov (United States)

    2016-07-01

    subject review. Pediatrics 101, 717–719 (1998). 8. McCullough, P. A., Wolyn, R., Rocher, L. L., Levin, R. N. & O’Neill, W. W. Acute renal failure...hyperpolarized silicon in the absence of the SPIONs. While HP 29Si signal could be observed during DNP, the signal was insufficient for high-field...space imaging using HP 3He and 129Xe in patients with chronic obstructive pulmonary disorder (COPD) or asthma10. 1.3 Solid-State Dynamic Nuclear

  5. Vascular targeting of nanoparticles for molecular imaging of diseased endothelium.

    Science.gov (United States)

    Atukorale, Prabhani U; Covarrubias, Gil; Bauer, Lisa; Karathanasis, Efstathios

    2017-04-01

    This review seeks to highlight the enormous potential of targeted nanoparticles for molecular imaging applications. Being the closest point-of-contact, circulating nanoparticles can gain direct access to targetable molecular markers of disease that appear on the endothelium. Further, nanoparticles are ideally suitable to vascular targeting due to geometrically enhanced multivalent attachment on the vascular target. This natural synergy between nanoparticles, vascular targeting and molecular imaging can provide new avenues for diagnosis and prognosis of disease with quantitative precision. In addition to the obvious applications of targeting molecular signatures of vascular diseases (e.g., atherosclerosis), deep-tissue diseases often manifest themselves by continuously altering and remodeling their neighboring blood vessels (e.g., cancer). Thus, the remodeled endothelium provides a wide range of targets for nanoparticles and molecular imaging. To demonstrate the potential of molecular imaging, we present a variety of nanoparticles designed for molecular imaging of cancer or atherosclerosis using different imaging modalities. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. A Targeted Mulifunctional Platform for Imaging and Treatment of Breast Cancer and Its Metastases Based on Adenoviral Vectors and Magnetic Nanoparticles

    National Research Council Canada - National Science Library

    Everts, Maaike

    2008-01-01

    ...) techniques and tumor treatment by heating after exposure to an alternating magnetic field. However, selective targeting of the nanoparticles to the tumor cells needs to be accomplished before the imaging or therapy can be successful...

  7. A Targeted Multifunctional Platform for Imaging and Treatment of Breast Cancer and Its Metastases Based on Adenoviral Vectors and Magnetic Nanoparticles

    National Research Council Canada - National Science Library

    Everts, Maaike; Saini, Vaibhav

    2007-01-01

    ...) techniques and tumor treatment by heating after exposure to an alternating magnetic field. However, selective targeting of the nanoparticles to the tumor cells needs to be accomplished before the imaging or therapy can be successful...

  8. Systemic Targeted Alpha Radiotherapy for Cancer

    Directory of Open Access Journals (Sweden)

    Allan B. J.

    2013-09-01

    Full Text Available Background: The fundamental principles of internal targeted alpha therapy for cancer were established many decades ago.The high linear energy transfer (LET of alpha radiation to the targeted cancer cellscauses double strand breaks in DNA. At the same time, the short range radiation spares adjacent normal tissues. This targeted approach complements conventional external beam radiotherapy and chemotherapy. Such therapies fail on several fronts, such as lack of control of some primary cancers (e.g.glioblastoma multiformeand to inhibit the development of lethal metastatic cancer after successful treatment of the primary cancer. Objective: This review charts the developing role of systemic high LET, internal radiation therapy. Method: Targeted alpha therapy is a rapidly advancing experimental therapy that holds promise to deliver high cytotoxicity to targeted cancer cells. Initially thought to be indicated for leukemia and micrometastases, there is now evidence that solid tumors can also be regressed. Results: Alpha therapy may be molecular or physiological in its targeting. Alpha emitting radioisotopes such as Bi-212, Bi-213, At-211 and Ac-225 are used to label monoclonal antibodies or proteins that target specifc cancer cells. Alternatively, Radium-233 is used for palliative therapy of breast and prostate cancers because of its bone seeking properties. Conclusion: Preclinical studies and clinical trials of alpha therapy are discussed for leukemia, lymphoma, melanoma, glioblastoma multiforme, bone metastases, ovarian cancer, pancreatic cancer and other cancers.

  9. Magnetic resonance imaging-targeted, 3D transrectal ultrasound-guided fusion biopsy for prostate cancer: Quantifying the impact of needle delivery error on diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Peter R., E-mail: pmarti46@uwo.ca [Department of Medical Biophysics, The University of Western Ontario, London, Ontario N6A 3K7 (Canada); Cool, Derek W. [Department of Medical Imaging, The University of Western Ontario, London, Ontario N6A 3K7, Canada and Robarts Research Institute, The University of Western Ontario, London, Ontario N6A 3K7 (Canada); Romagnoli, Cesare [Department of Medical Imaging, The University of Western Ontario, London, Ontario N6A 3K7 (Canada); Fenster, Aaron [Department of Medical Biophysics, The University of Western Ontario, London, Ontario N6A 3K7 (Canada); Department of Medical Imaging, The University of Western Ontario, London, Ontario N6A 3K7 (Canada); Robarts Research Institute, The University of Western Ontario, London, Ontario N6A 3K7 (Canada); Ward, Aaron D. [Department of Medical Biophysics, The University of Western Ontario, London, Ontario N6A 3K7 (Canada); Department of Oncology, The University of Western Ontario, London, Ontario N6A 3K7 (Canada)

    2014-07-15

    Purpose: Magnetic resonance imaging (MRI)-targeted, 3D transrectal ultrasound (TRUS)-guided “fusion” prostate biopsy intends to reduce the ∼23% false negative rate of clinical two-dimensional TRUS-guided sextant biopsy. Although it has been reported to double the positive yield, MRI-targeted biopsies continue to yield false negatives. Therefore, the authors propose to investigate how biopsy system needle delivery error affects the probability of sampling each tumor, by accounting for uncertainties due to guidance system error, image registration error, and irregular tumor shapes. Methods: T2-weighted, dynamic contrast-enhanced T1-weighted, and diffusion-weighted prostate MRI and 3D TRUS images were obtained from 49 patients. A radiologist and radiology resident contoured 81 suspicious regions, yielding 3D tumor surfaces that were registered to the 3D TRUS images using an iterative closest point prostate surface-based method to yield 3D binary images of the suspicious regions in the TRUS context. The probabilityP of obtaining a sample of tumor tissue in one biopsy core was calculated by integrating a 3D Gaussian distribution over each suspicious region domain. Next, the authors performed an exhaustive search to determine the maximum root mean squared error (RMSE, in mm) of a biopsy system that gives P ≥ 95% for each tumor sample, and then repeated this procedure for equal-volume spheres corresponding to each tumor sample. Finally, the authors investigated the effect of probe-axis-direction error on measured tumor burden by studying the relationship between the error and estimated percentage of core involvement. Results: Given a 3.5 mm RMSE for contemporary fusion biopsy systems,P ≥ 95% for 21 out of 81 tumors. The authors determined that for a biopsy system with 3.5 mm RMSE, one cannot expect to sample tumors of approximately 1 cm{sup 3} or smaller with 95% probability with only one biopsy core. The predicted maximum RMSE giving P ≥ 95% for each

  10. Magnetic resonance imaging-targeted, 3D transrectal ultrasound-guided fusion biopsy for prostate cancer: Quantifying the impact of needle delivery error on diagnosis.

    Science.gov (United States)

    Martin, Peter R; Cool, Derek W; Romagnoli, Cesare; Fenster, Aaron; Ward, Aaron D

    2014-07-01

    Magnetic resonance imaging (MRI)-targeted, 3D transrectal ultrasound (TRUS)-guided "fusion" prostate biopsy intends to reduce the ∼23% false negative rate of clinical two-dimensional TRUS-guided sextant biopsy. Although it has been reported to double the positive yield, MRI-targeted biopsies continue to yield false negatives. Therefore, the authors propose to investigate how biopsy system needle delivery error affects the probability of sampling each tumor, by accounting for uncertainties due to guidance system error, image registration error, and irregular tumor shapes. T2-weighted, dynamic contrast-enhanced T1-weighted, and diffusion-weighted prostate MRI and 3D TRUS images were obtained from 49 patients. A radiologist and radiology resident contoured 81 suspicious regions, yielding 3D tumor surfaces that were registered to the 3D TRUS images using an iterative closest point prostate surface-based method to yield 3D binary images of the suspicious regions in the TRUS context. The probabilityP of obtaining a sample of tumor tissue in one biopsy core was calculated by integrating a 3D Gaussian distribution over each suspicious region domain. Next, the authors performed an exhaustive search to determine the maximum root mean squared error (RMSE, in mm) of a biopsy system that gives P ≥ 95% for each tumor sample, and then repeated this procedure for equal-volume spheres corresponding to each tumor sample. Finally, the authors investigated the effect of probe-axis-direction error on measured tumor burden by studying the relationship between the error and estimated percentage of core involvement. Given a 3.5 mm RMSE for contemporary fusion biopsy systems,P ≥ 95% for 21 out of 81 tumors. The authors determined that for a biopsy system with 3.5 mm RMSE, one cannot expect to sample tumors of approximately 1 cm(3) or smaller with 95% probability with only one biopsy core. The predicted maximum RMSE giving P ≥ 95% for each tumor was consistently greater when using

  11. Magnetic resonance imaging-targeted, 3D transrectal ultrasound-guided fusion biopsy for prostate cancer: Quantifying the impact of needle delivery error on diagnosis

    International Nuclear Information System (INIS)

    Martin, Peter R.; Cool, Derek W.; Romagnoli, Cesare; Fenster, Aaron; Ward, Aaron D.

    2014-01-01

    Purpose: Magnetic resonance imaging (MRI)-targeted, 3D transrectal ultrasound (TRUS)-guided “fusion” prostate biopsy intends to reduce the ∼23% false negative rate of clinical two-dimensional TRUS-guided sextant biopsy. Although it has been reported to double the positive yield, MRI-targeted biopsies continue to yield false negatives. Therefore, the authors propose to investigate how biopsy system needle delivery error affects the probability of sampling each tumor, by accounting for uncertainties due to guidance system error, image registration error, and irregular tumor shapes. Methods: T2-weighted, dynamic contrast-enhanced T1-weighted, and diffusion-weighted prostate MRI and 3D TRUS images were obtained from 49 patients. A radiologist and radiology resident contoured 81 suspicious regions, yielding 3D tumor surfaces that were registered to the 3D TRUS images using an iterative closest point prostate surface-based method to yield 3D binary images of the suspicious regions in the TRUS context. The probabilityP of obtaining a sample of tumor tissue in one biopsy core was calculated by integrating a 3D Gaussian distribution over each suspicious region domain. Next, the authors performed an exhaustive search to determine the maximum root mean squared error (RMSE, in mm) of a biopsy system that gives P ≥ 95% for each tumor sample, and then repeated this procedure for equal-volume spheres corresponding to each tumor sample. Finally, the authors investigated the effect of probe-axis-direction error on measured tumor burden by studying the relationship between the error and estimated percentage of core involvement. Results: Given a 3.5 mm RMSE for contemporary fusion biopsy systems,P ≥ 95% for 21 out of 81 tumors. The authors determined that for a biopsy system with 3.5 mm RMSE, one cannot expect to sample tumors of approximately 1 cm 3 or smaller with 95% probability with only one biopsy core. The predicted maximum RMSE giving P ≥ 95% for each tumor was

  12. Prostate zonal anatomy correlates with the detection of prostate cancer on multiparametric magnetic resonance imaging/ultrasound fusion-targeted biopsy in patients with a solitary PI-RADS v2-scored lesion.

    Science.gov (United States)

    Syed, Jamil S; Nguyen, Kevin A; Nawaf, Cayce B; Bhagat, Ansh M; Huber, Steffen; Levi, Angelique; Humphrey, Peter; Weinreb, Jeffrey C; Schulam, Peter G; Sprenkle, Preston C

    2017-09-01

    To evaluate the positive predictive value (PPV) of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) assessment method in patients with a single suspicious finding on prostate multiparametric magnetic resonance imaging (mpMRI). A total of 176 patients underwent MRI/ultrasound fusion-targeted prostate biopsy after the detection of a single suspicious finding on mpMRI. The PPV for cancer detection was determined based on PI-RADS v2 assessment score and location. Fusion biopsy detected prostate cancer in 60.2% of patients. Of these patients, 69.8% had Gleason score (GS) ≥7 prostate cancer. Targeted biopsy detected 90.5% of all GS≥7 prostate cancer. The PPV for GS≥7 detection of PI-RADS v2 category 5 (P5) and category 4 (P4) lesions was 70.2% and 37.7%, respectively. This increased to 88% and 38.5% for P5 and P4 lesions in the peripheral zone (PZ), respectively. Targeted biopsy did not miss GS≥7 disease compared with systematic biopsy in P5 lesions in the PZ and transition zone. The PPV of PI-RADS v2 for prostate cancer in patients with a single lesion on mpMRI is dependent on PI-RADS assessment category and location. The highest PPV was for a P5 lesion in the PZ. Published by Elsevier Inc.

  13. Bioengineering Strategies for Designing Targeted Cancer Therapies

    Science.gov (United States)

    Wen, Xuejun

    2014-01-01

    The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509

  14. Screening for Novel Drug Targets in Cancer

    NARCIS (Netherlands)

    Nijwening, J.H.

    2012-01-01

    Most cancer drugs are not specific enough, causing unwanted side effects and recurrence of treated tumors. Some modern cancer drugs, the so-called targeted therapeutics, specifically target tumor cells, while leaving normal and healthy cells unharmed. The aim of the research described in this thesis

  15. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative Treatments and Therapeutic Modalities)

    Science.gov (United States)

    2010-02-01

    Gennaro Daniele, Fortunato Ciardiello, Giampaolo Tortora : Rational combination of targeted therapies as a strategy to overcome the mechanisms of...16. Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. NEnglJMed 2008;358:1160^74. 17.Cappuzzo F, Ardizzoni A, Soto-Parra H, et al. Epider

  16. Prospects of targeting the gastrin releasing peptide receptor and somatostatin receptor 2 for nuclear imaging and therapy in metastatic breast cancer

    NARCIS (Netherlands)

    Dalm, Simone U.; Schrijver, Willemijne A M E; Sieuwerts, Anieta M.; Look, Maxime P.; Ziel-Van Der Made, Angelique C J; De Weerd, Vanja; Martens, John W.; Van Diest, Paul J.; De Jong, Marion; Van Deurzen, Carolien H M

    2017-01-01

    Background The gastrin releasing peptide receptor (GRPR) and the somatostatin receptor 2 (SSTR2) are overexpressed on primary breast cancer (BC), making them ideal candidates for receptor- mediated nuclear imaging and therapy. The aim of this study was to determine whether these receptors are also

  17. Cancer metabolism as a therapeutic target.

    Science.gov (United States)

    Batra, Surabhi; Adekola, Kehinde U A; Rosen, Steven T; Shanmugam, Mala

    2013-05-01

    Cancer is now recognized to be a disease arising from both genetic and metabolic abnormalities. In the mid-1900s, Otto Warburg described the phenomenon of elevated glucose consumption and aerobic glycolysis, and the dependence of cancer cells on this phenomenon for proliferation and growth. The Warburg effect has formed the basis of such diagnostic and prognostic imaging modalities as positron emission tomography (PET); however, we have not yet capitalized on this phenomenon for therapy. Several mechanisms have now been shown to contribute to the Warburg effect.Ongoing studies are attempting to understand the reasons that tumor cells engage in aerobic glycolysis in lieu of oxidative phosphorylation, and the advantages that accrue to them as a result. In this review, we discuss known benefits to tumor cells from this metabolic switch, and we highlight key enzymes that play a role in aerobic glycolysis. We also describe novel therapeutic options targeting glucose metabolism and the importance of continuing to understand the metabolic plasticity of cancer.

  18. Targeting the tumor microenvironment for cancer therapy.

    Science.gov (United States)

    Sounni, Nor Eddine; Noel, Agnès

    2013-01-01

    With the emergence of the tumor microenvironment as an essential ingredient of cancer malignancy, therapies targeting the host compartment of tumors have begun to be designed and applied in the clinic. The malignant features of cancer cells cannot be manifested without an important interplay between cancer cells and their local environment. The tumor infiltrate composed of immune cells, angiogenic vascular cells, lymphatic endothelial cells, and cancer-associated fibroblastic cells contributes actively to cancer progression. The ability to change these surroundings is an important property by which tumor cells are able to acquire some of the hallmark functions necessary for tumor growth and metastatic dissemination. Thus in the clinical setting the targeting of the tumor microenvironment to encapsulate or destroy cancer cells in their local environment has become mandatory. The variety of stromal cells, the complexity of the molecular components of the tumor stroma, and the similarity with normal tissue present huge challenges for therapies targeting the tumor microenvironment. These issues and their interplay are addressed in this review. After a decade of intensive clinical trials targeting cellular components of the tumor microenvironment, more recent investigations have shed light on the important role in cancer progression played by the noncellular stromal compartment composed of the extracellular matrix. A better understanding of how the tumor environment affects cancer progression should provide new targets for the isolation and destruction of cancer cells via interference with the complex crosstalk established between cancer cells, host cells, and their surrounding extracellular matrix. © 2012 American Association for Clinical Chemistry

  19. New Prostate Cancer Treatment Target

    Science.gov (United States)

    Researchers have identified a potential alternative approach to blocking a key molecular driver of an advanced form of prostate cancer, called androgen-independent or castration-resistant prostate cancer.

  20. Targeting glucose metabolism in patients with cancer.

    Science.gov (United States)

    Elf, Shannon E; Chen, Jing

    2014-03-15

    Nearly a century ago, Otto Warburg made the astute observation that the metabolic properties of cancer cells differ markedly from those of normal cells. Several decades passed before the concept of exploiting cancer cell metabolism came into clinical practice with the advent of chemotherapy, the underlying principle of which is to target rapidly dividing cells by interfering with critical processes that are all, on some level, driven by cell metabolism. Although chemotherapy can be quite effective, success rates are highly variable and the adverse effects associated with treatment often outweigh the benefits due to the fact that chemotherapy is indiscriminately cytotoxic against all rapidly dividing cells, cancerous or healthy. During the past several years, a more intricate understanding of cancer cell metabolism has permitted the development of targeted therapies that aim to specifically target cancer cells and spare healthy tissue by exploiting the altered metabolism of cancer cells. The identification of new metabolic targets and the subsequent development of small-molecule inhibitors of metabolic enzymes have demonstrated the utility and promise of targeting cancer cell metabolism as an anticancer strategy. This review summarizes recent advances in the identification and characterization of several metabolic enzymes as emerging anticancer targets. © 2013 American Cancer Society.

  1. Imaging Mouse Models of Cancer.

    Science.gov (United States)

    Lyons, Scott Keith

    2015-01-01

    Mouse models of cancer have proven to be an indispensable resource in furthering both our basic knowledge of cancer biology and the translation of new cancer treatments and imaging approaches into the clinic. As mouse models have developed and improved in their ability to model many diverse aspects of the human disease, so too has the need for robust imaging approaches to measure key biological parameters noninvasively. The aim of this review is to provide a brief overview of the various imaging approaches available to researchers today for imaging preclinical cancer models, highlighting their relative strengths and weaknesses. The very nature of modeling cancer in the mouse is also changing, and brief mention will be made on how imaging can maximize the utility of these new, accurate, and genetically versatile models.

  2. Theranostics Targeting Metastatic Breast Cancer

    Science.gov (United States)

    2016-10-01

    Clinical Cancer Res 2009;15(10):3574–3582. 37. de Bruin M, Miyake K, Litman T, Robey R, Bates SE. Reversal of resistance by GF120918 in cell lines...receptor type alpha in relation to cell type, malignancy, and differentiation in ovary, uterus, and cervix . Cancer Epidemiol Biomarkers Prev 1999;8(9... cancer . Steroids 2014. 242. Zafrani B, Aubriot MH, Mouret E, De Cremoux P, De Rycke Y, Nicolas A, Boudou E, Vincent- Salomon A, Magdelenat H, Sastre

  3. Vascular Targeting of a Gold Nanoparticle to Breast Cancer Metastasis.

    Science.gov (United States)

    Peiris, Pubudu M; Deb, Partha; Doolittle, Elizabeth; Doron, Gilad; Goldberg, Amy; Govender, Priya; Shah, Shruti; Rao, Swetha; Carbone, Sarah; Cotey, Thomas; Sylvestre, Meilyn; Singh, Sohaj; Schiemann, William P; Lee, Zhenghong; Karathanasis, Efstathios

    2015-08-01

    The vast majority of breast cancer deaths are due to metastatic disease. Although deep tissue targeting of nanoparticles is suitable for some primary tumors, vascular targeting may be a more attractive strategy for micrometastasis. This study combined a vascular targeting strategy with the enhanced targeting capabilities of a nanoparticle to evaluate the ability of a gold nanoparticle (AuNP) to specifically target the early spread of metastatic disease. As a ligand for the vascular targeting strategy, we utilized a peptide targeting alpha(v) beta(3) integrin, which is functionally linked to the development of micrometastases at a distal site. By employing a straightforward radiolabeling method to incorporate Technetium-99m into the AuNPs, we used the high sensitivity of radionuclide imaging to monitor the longitudinal accumulation of the nanoparticles in metastatic sites. Animal and histological studies showed that vascular targeting of the nanoparticle facilitated highly accurate targeting of micrometastasis in the 4T1 mouse model of breast cancer metastasis using radionuclide imaging and a low dose of the nanoparticle. Because of the efficient targeting scheme, 14% of the injected AuNP deposited at metastatic sites in the lungs within 60 min after injection, indicating that the vascular bed of metastasis is a viable target site for nanoparticles. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  4. Nanoparticles target early-stage breast cancer metastasis in vivo

    Science.gov (United States)

    Goldman, Evgeniya; Zinger, Assaf; da Silva, Dana; Yaari, Zvi; Kajal, Ashima; Vardi-Oknin, Dikla; Goldfeder, Mor; Schroeder, Josh E.; Shainsky-Roitman, Janna; Hershkovitz, Dov; Schroeder, Avi

    2017-10-01

    Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. In this study we demonstrate that 100 nm liposomes target triple-negative murine breast-cancer metastases post intravenous administration. Metastatic breast cancer was induced in BALB/c mice either experimentally, by a tail vein injection of 4T1 cells, or spontaneously, after implanting a primary tumor xenograft. To track their biodistribution in vivo the liposomes were labeled with multi-modal diagnostic agents, including indocyanine green and rhodamine for whole-animal fluorescent imaging, gadolinium for magnetic resonance imaging (MRI), and europium for a quantitative biodistribution analysis. The accumulation of liposomes in the metastases peaked at 24 h post the intravenous administration, similar to the time they peaked in the primary tumor. The efficiency of liposomal targeting to the metastatic tissue exceeded that of a non-liposomal agent by 4.5-fold. Liposomes were detected at very early stages in the metastatic progression, including metastatic lesions smaller than 2 mm in diameter. Surprisingly, while nanoparticles target breast cancer metastasis, they may also be found in elevated levels in the pre-metastatic niche, several days before metastases are visualized by MRI or histologically in the tissue. This study highlights the promise of diagnostic and therapeutic nanoparticles for treating metastatic cancer, possibly even for preventing the onset of the metastatic dissemination by targeting the pre-metastatic niche.

  5. Nanoplatforms for magnetic resonance imaging of cancer

    International Nuclear Information System (INIS)

    Cywinska, M. A.; Grudzinski, I. P.; Cieszanowski, A.; Bystrzejewski, M.; Poplawska, M.

    2011-01-01

    The application of biomedical nanotechnology in magnetic resonance imaging (MRI) is expect to have a major impact leading to the development of new contrast drug candidates on the nanoscale (1 - 100 nm) that are able to react with specific biological targets at a molecular level. One of the major challenges in this regard is the construction of nanomaterials, especially used in molecular MRI diagnostics of cancer in vivo, specialized antitumor drug delivery or real-time evaluation of the efficacy of the implemented cancer treatment. In this paper, we tried to gain further insights into current trends of nanomedicine, with special focus on preclinical MRI studies in translation cancer research. (authors)

  6. Targeting TMPRSS2-ERG in Prostate Cancer

    Science.gov (United States)

    2017-11-01

    AWARD NUMBER: W81XWH-13-1-0212 TITLE: Targeting TMPRSS2-ERG in Prostate Cancer PRINCIPAL INVESTIGATOR: David Takeda CONTRACTING...ORGANIZATION: Dana-Farber Cancer Institute Boston, MA 02215 REPORT DATE: November 2017 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical Research...Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0212 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David Takeda 5d. PROJECT NUMBER 5e

  7. In Vivo Imaging of Molecularly Targeted Phage

    Directory of Open Access Journals (Sweden)

    Kimberly A. Kelly

    2006-12-01

    Full Text Available Rapid identification of in vivo affinity ligands would have far-reaching applications for imaging specific molecular targets, in vivo systems imaging, and medical use. We have developed a high-throughput method for identifying and optimizing ligands to map and image biologic targets of interest in vivo. We directly labeled viable phage clones with far-red fluorochromes and comparatively imaged them in vivo by multichannel fluorescence ratio imaging. Using Secreted Protein Acidic and Rich in Cysteine (osteonectin and vascular cell adhesion molecule-1 as model targets, we show that: 1 fluorescently labeled phage retains target specificity on labeling; 2 in vivo distribution can be quantitated (detection thresholds of ~ 300 phage/mm3 tissue throughout the entire depth of the tumor using fluorescent tomographic imaging; and 3 fluorescently labeled phage itself can serve as a replenishable molecular imaging agent. The described method should find widespread application in the rapid in vivo discovery and validation of affinity ligands and, importantly, in the use of fluorochrome-labeled phage clones as in vivo imaging agents.

  8. Optical imaging for breast cancer prescreening

    Directory of Open Access Journals (Sweden)

    Godavarty A

    2015-07-01

    Full Text Available Anuradha Godavarty,1 Suset Rodriguez,1 Young-Jin Jung,2 Stephanie Gonzalez1 1Optical Imaging Laboratory, Department of Biomedical Engineering, Florida International University, Miami, FL, USA; 2Department of Radiological Science, Dongseo University, Busan, South Korea Abstract: Breast cancer prescreening is carried out prior to the gold standard screening using X-ray mammography and/or ultrasound. Prescreening is typically carried out using clinical breast examination (CBE or self-breast examinations (SBEs. Since CBE and SBE have high false-positive rates, there is a need for a low-cost, noninvasive, non-radiative, and portable imaging modality that can be used as a prescreening tool to complement CBE/SBE. This review focuses on the various hand-held optical imaging devices that have been developed and applied toward early-stage breast cancer detection or as a prescreening tool via phantom, in vivo, and breast cancer imaging studies. Apart from the various optical devices developed by different research groups, a wide-field fiber-free near-infrared optical scanner has been developed for transillumination-based breast imaging in our Optical Imaging Laboratory. Preliminary in vivo studies on normal breast tissues, with absorption-contrasted targets placed in the intramammary fold, detected targets as deep as 8.8 cm. Future work involves in vivo imaging studies on breast cancer subjects and comparison with the gold standard X-ray mammography approach. Keywords: diffuse optical imaging, near-infrared, hand-held devices, breast cancer, prescreening, early detection 

  9. Targets for molecular therapy of skin cancer.

    Science.gov (United States)

    Green, Cheryl L; Khavari, Paul A

    2004-02-01

    Cancers of the skin encompass the first and second most common neoplasms in the United States, epidermal basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), respectively, as well as the melanocytic malignancy, malignant melanoma (MM). Recently identified alterations in the function of specific genes in these cancers provide new potential therapeutic targets. These alterations affect conserved regulators of cellular proliferation and viability, including the Sonic Hedgehog, Ras/Raf, ARF/p53, p16(INK4A)/CDK4/Rb and NF-kappaB pathways. New modalities designed to target these specific proteins may represent promising approaches to therapy of human skin cancers.

  10. Color-coded intravital imaging demonstrates a transforming growth factor-β (TGF-β) antagonist selectively targets stromal cells in a human pancreatic-cancer orthotopic mouse model.

    Science.gov (United States)

    Murakami, Takashi; Hiroshima, Yukihiko; Miyake, Kentaro; Hwang, Ho Kyoung; Kiyuna, Tasuku; DeLong, Jonathan C; Lwin, Thinzar M; Matsuyama, Ryusei; Mori, Ryutaro; Kumamoto, Takafumi; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2017-05-19

    Pancreatic cancer is a recalcitrant malignancy, partly due to desmoplastic stroma which stimulates tumor growth, invasion, and metastasis, and inhibits chemotherapeutic drug delivery. Transforming growth factor-β (TGF-β) has an important role in the formation of stromal desmoplasia. The present study describes the ability of color-coded intravital imaging to demonstrate the efficacy of a TGF-β inhibitor to target stroma in an orthotopic mouse model of pancreatic cancer. The BxPC-3 human pancreatic adenocarcinoma cell line expressing green fluorescent protein (GFP), which also has a high TGF-β expression level, was used in an orthotopic model in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP). Fourteen mice were randomized into a control group (n = 7, vehicle, i.p., weekly, for 3 weeks) and a treated group (n = 7, SB431542 [TGF-β receptor type I inhibitor] 0.3 mg, i.p., weekly, for 3 weeks). Stromal cells expressing RFP and cancer cells expressing GFP were observed weekly for 3 weeks by real-time color-coded intravital imaging. The RFP fluorescence area from the stromal cells, relative to the GFP fluorescence area of the cancer cells, was significantly decreased in the TGF-β-inhibitor-treatment group compared to the control group. The present study demonstrated color-coded imaging in an orthotopic pancreatic-cancer cell-line mouse model can readily detect the selective anti-stromal-cell targeting of a TGF-β inhibitor.

  11. Functional genomics and cancer drug target discovery.

    Science.gov (United States)

    Moody, Susan E; Boehm, Jesse S; Barbie, David A; Hahn, William C

    2010-06-01

    The recent development of technologies for whole-genome sequencing, copy number analysis and expression profiling enables the generation of comprehensive descriptions of cancer genomes. However, although the structural analysis and expression profiling of tumors and cancer cell lines can allow the identification of candidate molecules that are altered in the malignant state, functional analyses are necessary to confirm such genes as oncogenes or tumor suppressors. Moreover, recent research suggests that tumor cells also depend on synthetic lethal targets, which are not mutated or amplified in cancer genomes; functional genomics screening can facilitate the discovery of such targets. This review provides an overview of the tools available for the study of functional genomics, and discusses recent research involving the use of these tools to identify potential novel drug targets in cancer.

  12. Targeting calcium signaling in cancer therapy

    Directory of Open Access Journals (Sweden)

    Chaochu Cui

    2017-01-01

    Full Text Available The intracellular calcium ions (Ca2+ act as second messenger to regulate gene transcription, cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca2+ homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis, progression and metastasis. Targeting derailed Ca2+ signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca2+ channels, transporters and Ca2+-ATPases, which have been reported to be altered in human cancer patients. It discusses the current research effort toward evaluation of the blockers, inhibitors or regulators for Ca2+ channels/transporters or Ca2+-ATPase pumps as anti-cancer drugs. This review is also aimed to stimulate interest in, and support for research into the understanding of cellular mechanisms underlying the regulation of Ca2+ signaling in different cancer cells, and to search for novel therapies to cure these malignancies by targeting Ca2+ channels or transporters.

  13. Photoacoustic imaging of prostate cancer

    Directory of Open Access Journals (Sweden)

    Xuanjin Yang

    2017-07-01

    Full Text Available Photoacoustic imaging (PAI, also known as optoacoustic imaging, is a rapidly growing imaging modality with potential in medical diagnosis and therapy monitoring. This paper focuses on the techniques of prostate PAI and its potential applications in prostate cancer detection. Transurethral light delivery combined with transrectal ultrasound detection overcomes light scattering in the surrounding tissue and provides optimal photoacoustic signals while minimizing invasiveness. While label-free PAI based on endogenous contrast has promising potential for prostate cancer detection, exogenous contrast agents can further enhance the sensitivity and specificity of prostate cancer PAI. Further in vivo studies are required in order to achieve the translation of prostate PAI to clinical implementation. The minimal invasiveness, relatively low cost, high specificity and sensitivity, and real-time imaging capability are valuable advantages of PAI that may improve the current prostate cancer management in clinic.

  14. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Barnkob, Mike Stein

    2014-01-01

    cancer immunotherapies has yet to be fulfilled. The insufficient efficacy of existing treatments can be attributed to a number of biological and technical issues. In this review, we detail the current limitations of immunotherapy target selection and design, and review computational methods to streamline...... therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes...

  15. Immunologic Targeting Of Cancer Cells

    Science.gov (United States)

    T.; Chen, M. R.; Linden, R.

    1989-06-01

    A number of laboratories have demonstrated that immunoconjugates may have potential in phototherapy of cancer. The phototoxic effectiveness of these conjugates may be increased by manipulation of irradiation parameters and by biochemical and immunologic modulation. Results from experiments aimed at potentiation of immunoconjugate photosensitization are presented.

  16. Targeting mitochondria for cancer treatment

    Czech Academy of Sciences Publication Activity Database

    Pokorný, Jiří; Cifra, Michal; Jandová, Anna; Kučera, Ondřej; Šrobár, Fedor; Vrba, J.; Vrba, J.; Kobilková, J.

    2012-01-01

    Roč. 17, č. 1 (2012), s. 23-36 ISSN 1128-6598 R&D Projects: GA ČR(CZ) GAP102/11/0649; GA ČR GAP102/10/0120 Institutional support: RVO:67985882 Keywords : Electromagnetic fields * Cellular biophysics * Cancer Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 0.750, year: 2012

  17. Cancer immunotherapy: nanodelivery approaches for immune cell targeting and tracking

    Science.gov (United States)

    Conniot, João; Silva, Joana; Fernandes, Joana; Silva, Liana; Gaspar, Rogério; Brocchini, Steve; Florindo, Helena; Barata, Teresa

    2014-11-01

    Cancer is one of the most common diseases afflicting people globally. New therapeutic approaches are needed due to the complexity of cancer as a disease. Many current treatments are very toxic and have modest efficacy at best. Increased understanding of tumor biology and immunology has allowed the development of specific immunotherapies with minimal toxicity. It is important to highlight the performance of monoclonal antibodies, immune adjuvants, vaccines and cell-based treatments. Although these approaches have shown varying degrees of clinical efficacy, they illustrate the potential to develop new strategies. Targeted immunotherapy is being explored to overcome the heterogeneity of malignant cells and the immune suppression induced by both the tumor and its microenvironment. Nanodelivery strategies seek to minimize systemic exposure to target therapy to malignant tissue and cells. Intracellular penetration has been examined through the use of functionalized particulates. These nano-particulate associated medicines are being developed for use in imaging, diagnostics and cancer targeting. Although nano-particulates are inherently complex medicines, the ability to confer, at least in principle, different types of functionality allows for the plausible consideration these nanodelivery strategies can be exploited for use as combination medicines. The development of targeted nanodelivery systems in which therapeutic and imaging agents are merged into a single platform is an attractive strategy. Currently, several nanoplatform-based formulations, such as polymeric nanoparticles, micelles, liposomes and dendrimers are in preclinical and clinical stages of development. Herein, nanodelivery strategies presently investigated for cancer immunotherapy, cancer targeting mechanisms and nanocarrier functionalization methods will be described. We also intend to discuss the emerging nano-based approaches suitable to be used as imaging techniques and as cancer treatment options.

  18. Low density lipoproteins mediated nanoplatforms for cancer targeting

    International Nuclear Information System (INIS)

    Jain, Anupriya; Jain, Keerti; Kesharwani, Prashant; Jain, Narendra K.

    2013-01-01

    Chemotherapy is a foremost remedial approach for the treatment of localized and metastasized tumors. In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. One such difference may be that of increased receptor-mediated cellular uptake of low density lipoproteins (LDLs) by cancer cells. Lipoproteins in general and specifically LDL are ideal candidates for loading and delivering cancer therapeutic and diagnostic agents due to their biocompatibility. By mimicking the endogenous shape and structure of lipoproteins, the reconstituted lipoproteins can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body’s defenses. In this account, we review the field of low density inspired nanoparticles in relation to the delivery of cancer imaging and therapeutic agents. LDL has instinctive cancer targeting potential and has been used to incorporate various lipophillic molecules to transport them to tumors. Nature’s method of rerouting LDL provides a strategy to extend the cancer targeting potential of lipoproteins far off its constricted purview. In this review, we have discussed the various aspects of LDL including its role in cancer imaging and chemotherapy in retrospect and prospect and current efforts aimed to further improve the delivery efficacy of LDL–drug complexes with reduced chances of drug resistance leading to optimal drug delivery. This review provides a strong support for the concept of using LDL as a drug carrier

  19. Magnetic Targeting and Delivery of Drug-Loaded SWCNTs Theranostic Nanoprobes to Lung Metastasis in Breast Cancer Animal Model: Noninvasive Monitoring Using Magnetic Resonance Imaging.

    Science.gov (United States)

    Al Faraj, Achraf; Shaik, Asma Sultana; Halwani, Rabih; Alfuraih, Abdulrahman

    2016-06-01

    In this study, we aimed to develop novel therapeutic and diagnostic approaches by improving the targeting of doxorubicin-loaded single-walled carbon nanotubes (SWCNTs) to metastatic regions, and monitor their preferential homing and enhanced therapeutic effect using noninvasive free-breathing magnetic resonance imaging (MRI) and bioluminescence imaging. High-energy flexible magnets were specifically positioned over the metastatic tumor sites in the lungs. SWCNTs biodistribution, tumor progression, and subsequent treatment efficiency were assessed following administration of the magnetically attracted doxorubicin-loaded anti-CD105 conjugated nanocarriers. The use of high-energy magnets offered improved theranostic effect of doxorubicin-loaded nanocarriers, by magnetically targeting them towards metastatic tumor sites in the lungs. MRI allowed sensitive monitoring of nanocarriers biodistribution in the abdominal organs, their preferential homing towards the metastatic sites, and their enhanced therapeutic effect. Combination of noninvasive MRI to localize sensitively the tumor sites, with specific positioning of magnets that can enhance the magnetic targeting of nanocarriers, allowed increasing the treatment efficiency.

  20. Magnetic resonance imaging-targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta-analysis.

    Science.gov (United States)

    Schoots, Ivo G; Roobol, Monique J; Nieboer, Daan; Bangma, Chris H; Steyerberg, Ewout W; Hunink, M G Myriam

    2015-09-01

    Multiparametric magnetic resonance imaging (MRI) of the prostate may improve the diagnostic accuracy of prostate cancer detection in MRI-targeted biopsy (MRI-TBx) in comparison to transrectal ultrasound-guided biopsy (TRUS-Bx). Systematic review and meta-analysis of evidence regarding the diagnostic benefits of MRI-TBx versus TRUS-Bx in detection of overall prostate cancer (primary objective) and significant/insignificant prostate cancer (secondary objective). A systematic review of Embase, Medline, Web of Science, Scopus, PubMed, Cinahl, and the Cochrane library was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies criteria. Only men with a positive MRI were included. The reports we included (16 studies) used both MRI-TBx and TRUS-Bx for prostate cancer detection. A cumulative total of 1926 men with positive MRI were included, with prostate cancer prevalence of 59%. MRI-TBx and TRUS-Bx did not significantly differ in overall prostate cancer detection (sensitivity 0.85, 95% confidence interval [CI] 0.80-0.89, and 0.81, 95% CI 0.70-0.88, respectively). MRI-TBx had a higher rate of detection of significant prostate cancer compared to TRUS-Bx (sensitivity 0.91, 95% CI 0.87-0.94 vs 0.76, 95% CI 0.64-0.84) and a lower rate of detection of insignificant prostate cancer (sensitivity 0.44, 95% CI 0.26-0.64 vs 0.83, 95% confidence interval 0.77-0.87). Subgroup analysis revealed an improvement in significant prostate cancer detection by MRI-TBx in men with previous negative biopsy, rather than in men with initial biopsy (relative sensitivity 1.54, 95% CI 1.05-2.57 vs 1.10, 95% CI 1.00-1.22). Because of underlying methodological flaws of MRI-TBx, the comparison of MRI-TBx and TRUS-Bx needs to be regarded with caution. In men with clinical suspicion of prostate cancer and a subsequent positive MRI, MRI-TBx and

  1. Structural and functional imaging for vascular targeted photodynamic therapy

    Science.gov (United States)

    Li, Buhong; Gu, Ying; Wilson, Brian C.

    2017-02-01

    Vascular targeted photodynamic therapy (V-PDT) has been widely used for the prevention or treatment of vascular-related diseases, such as localized prostate cancer, wet age-related macular degeneration, port wine stains, esophageal varices and bleeding gastrointestinal mucosal lesions. In this study, the fundamental mechanisms of vascular responses during and after V-PDT will be introduced. Based on the V-PDT treatment of blood vessels in dorsal skinfold window chamber model, the structural and functional imaging, which including white light microscopy, laser speckle imaging, singlet oxygen luminescence imaging, and fluorescence imaging for evaluating vascular damage will be presented, respectively. The results indicate that vessel constriction and blood flow dynamics could be considered as the crucial biomarkers for quantitative evaluation of vascular damage. In addition, future perspectives of non-invasive optical imaging for evaluating vascular damage of V-PDT will be discussed.

  2. RLIP76 Targeted Therapy for Kidney Cancer.

    Science.gov (United States)

    Singhal, Sharad S; Singhal, Jyotsana; Figarola, James; Horne, David; Awasthi, Sanjay

    2015-10-01

    Despite recent improvements in chemotherapeutic approaches to treating kidney cancer, this malignancy remains deadly if not found and removed at an early stage of the disease. Kidney cancer is highly drug-resistant, which may at least partially result from high expression of transporter proteins in the cell membranes of kidney cells. Although these transporter proteins can contribute to drug-resistance, targeting proteins from the ATP-binding cassette transporter family has not been effective in reversing drug-resistance in kidney cancer. Recent studies have identified RLIP76 as a key stress-defense protein that protects normal cells from damage caused by stress conditions, including heat, ultra-violet light, X-irradiation, and oxidant/electrophilic toxic chemicals, and is crucial for protecting cancer cells from apoptosis. RLIP76 is the predominant glutathione-electrophile-conjugate (GS-E) transporter in cells, and inhibiting it with antibodies or through siRNA or antisense causes apoptosis in many cancer cell types. To date, blocking of RLIP76, either alone or in combination with chemotherapeutic drugs, as a therapeutic strategy for kidney cancer has not yet been evaluated in human clinical trials, although there is considerable potential for RLIP76 to be developed as a therapeutic agent for kidney cancer. In the present review, we discuss the mechanisms underlying apoptosis caused by RLIP76 depletion, the role of RLIP76 in clathrin-dependent endocytosis deficiency, and the feasibility of RLIP76-targeted therapy for kidney cancer.

  3. Radiological imaging of rectal cancer

    Directory of Open Access Journals (Sweden)

    Lidija Lincender-Cvijetić

    2012-11-01

    Full Text Available This article discusses the possibilities of diagnosing abdominal imaging in patients with rectal cancer, detecting lesions and assessing the stage of the lesions, in order to select the appropriate therapy. Before the introduction of imaging technologies, the diagnosis of colorectal pathology was based on conventional methods of inspecting intestines with a barium enema, with either a single or double contrast barium enema. Following the development of endoscopic methods and the wide use of colonoscopy, colonoscopy became the method of choice for diagnosing colorectal diseases. The improvement of Computerized Tomography (CT and Magnetic Resonance Imaging (MRI, gave us new possibilities for diagnosing colorectal cancer. For rectal cancer, trans-rectal US (TRUS or endo-anal US (EAUS have a significant role. For staging rectal cancer, the Multi Slice Computed Tomography (MSCT is not the method of choice, but Magnetic Resonance Imaging (MRI is preferred when it comes to monitoring the rectum. Therole of the MRI in the T staging of rectal cancer is crucial in preoperative assessment of: thickness – the width of the tumor, the extramural invasion, the circumference of resection margin (CRM, andthe assessment of the inclusion of mesorectal fascia. For successful execution of surgical techniques, good diagnostic imaging of the cancer is necessary in order to have a low level of recurrence. According to medical studies, the sensitivity of FDG-PET in diagnosing metastatic nodals is low, but for now it is not recommended in routine diagnosis of metastatic colorectal carcinoma.

  4. Clean image synthesis and target numerical marching for optical imaging with backscattering light.

    Science.gov (United States)

    Xu, Min; Pu, Yang; Wang, Wubao

    2011-03-14

    Scanning backscattering imaging and independent component analysis (ICA) are used to probe targets hidden in the subsurface of a turbid medium. A new correction procedure is proposed and used to synthesize a "clean" image of a homogeneous host medium numerically from a set of raster-scanned "dirty" backscattering images of the medium with embedded targets. The independent intensity distributions on the surface of the medium corresponding to individual targets are then unmixed using ICA of the difference between the set of dirty images and the clean image. The target positions are localized by a novel analytical method, which marches the target to the surface of the turbid medium until a match with the retrieved independent component is accomplished. The unknown surface property of the turbid medium is automatically accounted for by this method. Employing clean image synthesis and target numerical marching, three-dimensional (3D) localization of objects embedded inside a turbid medium using independent component analysis in a backscattering geometry is demonstrated for the first time, using as an example, imaging a small piece of cancerous prostate tissue embedded in a host consisting of normal prostate tissue.

  5. Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha

    Directory of Open Access Journals (Sweden)

    Weibo Cai Ph.D.

    2008-01-01

    Full Text Available Tumor necrosis factor-alpha (TNF-α, a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation.

  6. Preclinical evaluation of destruxin B as a novel Wnt signaling target suppressing proliferation and metastasis of colorectal cancer using non-invasive bioluminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Chi-Tai [Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan (China); Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (China); Rao, Yerra Koteswara [Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung, Taiwan (China); Ye, Min [Department of Natural Medicine, School of Pharmaceutical Sciences, Peking University, Beijing (China); Wu, Wen-Shi [Department of Horticulture and Biotechnology, Chinese Culture University, Taipei, Taiwan (China); Chang, Tung-Chen [Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (China); Wang, Liang-Shun [Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Division of Thoracic Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan (China); Wu, Chih-Hsiung [Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan (China); Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (China); Wu, Alexander T.H., E-mail: chaw1211@tmu.edu.tw [Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan (China); Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan (China); Tzeng, Yew-Min, E-mail: ymtzeng@cyut.edu.tw [Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung, Taiwan (China)

    2012-05-15

    In continuation to our studies toward the identification of direct anti-cancer targets, here we showed that destruxin B (DB) from Metarhizium anisopliae suppressed the proliferation and induced cell cycle arrest in human colorectal cancer (CRC) HT29, SW480 and HCT116 cells. Additionally, DB induced apoptosis in HT29 cells by decreased expression level of anti-apoptotic proteins Bcl-2 and Bcl-xL while increased pro-apoptotic Bax. On the other hand, DB attenuated Wnt-signaling by downregulation of β-catenin, Tcf4 and β-catenin/Tcf4 transcriptional activity, concomitantly with decreased expression of β-catenin target genes cyclin D1, c-myc and survivin. Furthermore, DB affected the migratory and invasive ability of HT29 cells through suppressed MMPs-2 and -9 enzymatic activities. We also found that DB targeted the MAPK and/or PI3K/Akt pathway by reduced expression of Akt, IKK-α, JNK, NF-κB, c-Jun and c-Fos while increased that of IκBα. Finally, we demonstrated that DB inhibited tumorigenesis in HT29 xenograft mice using non-invasive bioluminescence technique. Consistently, tumor samples from DB-treated mice demonstrated suppressed expression of β-catenin, cyclin D1, survivin, and endothelial marker CD31 while increased caspase-3 expression. Collectively, our data supports DB as an inhibitor of Wnt/β-catenin/Tcf signaling pathway that may be beneficial in the CRC management. Highlights: ► Destruxin B (DB) inhibited colorectal cancer cells growth and induced apoptosis. ► MAPK and/or PI3K/Akt cascade cooperates in DB induced apoptosis. ► DB affected the migratory and invasive ability of HT29 cells through MMP-9. ► DB attenuated Wnt-signaling components β-catenin, Tcf4. ► DB attenuated cyclin D1, c-myc, survivin and tumorigenesis in HT29 xenograft mice.

  7. Targeting AAC-11 in cancer therapy.

    Science.gov (United States)

    Faye, Audrey; Poyet, Jean-Luc

    2010-01-01

    Since its discovery in 1997, the antiapoptotic factor AAC-11 has rapidly gained attention due to its potential use in cancer therapy. Indeed, most cancer cells express elevated levels of AAC-11, which is now known to be involved in both tumor cells growth as well as sensitivity to chemotherapeutic drugs. In this review, we examine the most recent evidence about the role of AAC-11 in cancer biology and the therapeutic perspectives associated with its specific targeting. For that purpose, literature dealing with AAC-11 in the PubMed database was reviewed from 1997 up to date. AAC-11 is an antiapoptotic gene that has the potential to be a target for anti-cancer therapy, and warrants further investigation. As its expression seems to predict unfavorable prognosis, at least in some cancers, it also may become a potent prognostic marker. Blocking AAC-11 function in cancer for therapeutic purposes might be of great interest. The recent report of efficient AAC-11 inhibiting peptides that sensitize tumor cells to chemotherapeutic drugs has raise the exciting notion that AAC-11 might be a druggable target and fueled the search for new therapeutic agents that could block AAC-11 function.

  8. Biomarkers and Targeted Therapy in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Fataneh Karandish

    2016-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%–3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  9. Therapeutic Approaches to Target Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, Arlhee, E-mail: arlhee@cim.sld.cu; Leon, Kalet [Department of Systems Biology, Center of Molecular Immunology, 216 Street, PO Box 16040, Atabey, Havana 11600 (Cuba)

    2011-08-15

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC.

  10. Therapeutic Approaches to Target Cancer Stem Cells

    International Nuclear Information System (INIS)

    Diaz, Arlhee; Leon, Kalet

    2011-01-01

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC

  11. Image-Guided Cancer Nanomedicine

    OpenAIRE

    Dong-Hyun Kim

    2018-01-01

    Multifunctional nanoparticles with superior imaging properties and therapeutic effects have been extensively developed for the nanomedicine. However, tumor-intrinsic barriers and tumor heterogeneity have resulted in low in vivo therapeutic efficacy. The poor in vivo targeting efficiency in passive and active targeting of nano-therapeutics along with the toxicity of nanoparticles has been a major problem in nanomedicine. Recently, image-guided nanomedicine, which can deliver nanoparticles loca...

  12. Targeted treatments for cervical cancer: a review

    Directory of Open Access Journals (Sweden)

    Peralta-Zaragoza O

    2012-11-01

    Full Text Available Oscar Peralta-Zaragoza,1 Víctor Hugo Bermúdez-Morales,1 Carlos Pérez-Plasencia,2,3 Jonathan Salazar-León,1 Claudia Gómez-Cerón,1 Vicente Madrid-Marina11Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Cuernavaca, Morelos, México; 2Oncogenomics Laboratory, National Cancer Institute of Mexico, Tlalpan, México; 3Biomedicine Unit, FES-Iztacala UNAM, México City, MéxicoAbstract: Cervical cancer is the second most common cause of cancer death in women worldwide and the development of new diagnosis, prognostic, and treatment strategies merits special attention. Although surgery and chemoradiotherapy can cure 80%–95% of women with early stage cancer, the recurrent and metastatic disease remains a major cause of cancer death. Many efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent decades, research on treatment strategies has proposed several options, including the role of HPV E6 and E7 oncogenes, which are retained and expressed in most cervical cancers and whose respective oncoproteins are critical to the induction and maintenance of the malignant phenotype. Other efforts have been focused on antitumor immunotherapy strategies. It is known that during the development of cervical cancer, a cascade of abnormal events is induced, including disruption of cellular cycle control, perturbation of antitumor immune response, alteration of gene expression, and deregulation of microRNA expression. Thus, in this review article we discuss potential targets for the treatment of cervical cancer associated with HPV infection, with special attention to immunotherapy approaches, clinical trials, siRNA molecules, and their implications as gene therapy strategies against cervical cancer development.Keywords: Cervical cancer, clinical trials, gene therapy, HPV E6 and E7 oncogenes, siRNAs

  13. Lung cancer imaging

    CERN Document Server

    Ravenel, James G

    2013-01-01

    This book provides a guide to the diagnosis, staging and overview of the management of lung cancer relevant to practicing radiologists so that they can better understand the decision making issues and provide more useful communication to treating physicians.

  14. Imaging in early phase childhood cancer trials

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, Peter C. [Children' s Hospital of Philadelphia, Division of Clinical Pharmacology and Therapeutics, Philadelphia, PA (United States)

    2009-02-15

    Advances made in the treatment of childhood malignancies during the last four decades have resulted in overall cure rates of approximately 80%, but progress has slowed significantly during the last 10 years, underscoring the need for more effective and less toxic agents. Current research is focused on development of molecularly targeted agents, an era ushered in with the discovery of imatinib mesylate for the treatment of chronic myelogenous leukemia. Since imatinib's introduction into the clinic, an increasing number of tyrosine kinase inhibitors have been developed and entered into clinical trials and practice. Parallel to the initial advances made in molecularly targeted agents has been the development of a spectrum of novel imaging modalities. Future goals for imaging in childhood cancer research thus include (1) patient identification based on target identification or other biologic characteristics of the tumor, (2) assessing pharmacokinetic-pharmacodynamic (PK-PD) effects, and (3) predictive value with an early indication of patient benefit. Development and application of novel imaging modalities for children with cancer can serve to streamline development of molecularly targeted agents. (orig.)

  15. Targeted radionuclide therapies for pancreatic cancer.

    Science.gov (United States)

    Shah, M; Da Silva, R; Gravekamp, C; Libutti, S K; Abraham, T; Dadachova, E

    2015-08-01

    Pancreatic malignancies, the fourth leading cause of cancer deaths, have an aggressive behavior with poor prognosis, resulting in a 5-year survival rate of only 4%. It is typically a silent malignancy until patients develop metastatic disease. Targeted radionuclide therapies of cancer such as radiolabeled peptides, which bind to the receptors overexpressed by cancer cells and radiolabeled antibodies to tumor-specific antigens provide a viable alternative to chemotherapy and external beam radiation of metastatic cancers. Multiple clinical trials of targeted radionuclide therapy of pancreatic cancer have been performed in the last decade and demonstrated safety and potential efficacy of radionuclide therapy for treatment of this formidable disease. Although a lot of progress has been made in treatment of pancreatic neuroendocrine tumors with radiolabeled (90)Y and (177)Lu somatostatin peptide analogs, pancreatic adenocarcinomas remain a major challenge. Novel approaches such as peptides and antibodies radiolabeled with alpha emitters, pre-targeting, bispecific antibodies and biological therapy based on the radioactive tumorlytic bacteria might offer a potential breakthrough in treatment of pancreatic adenocarcinomas.

  16. Targeted Therapy for Biliary Tract Cancer

    International Nuclear Information System (INIS)

    Furuse, Junji; Okusaka, Takuji

    2011-01-01

    It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer, because most of these patients are unsuitable candidates for surgery, and even patients undergoing curative surgery often have recurrence. Recently, the combination of cisplatin plus gemcitabine was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. Thus, the combination of cisplatin plus gemcitabine is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective against biliary tract cancer. Although some targeted agents have been investigated as monotherapy for first-line chemotherapy, none were found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen and have been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogeneous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy, and international collaboration is important

  17. Targeted Therapy for Biliary Tract Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Furuse, Junji, E-mail: jfuruse@ks.kyorin-u.ac.jp [Department of Internal Medicine, Medical Oncology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo, 181-8611 (Japan); Okusaka, Takuji [Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2011-05-03

    It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer, because most of these patients are unsuitable candidates for surgery, and even patients undergoing curative surgery often have recurrence. Recently, the combination of cisplatin plus gemcitabine was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. Thus, the combination of cisplatin plus gemcitabine is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective against biliary tract cancer. Although some targeted agents have been investigated as monotherapy for first-line chemotherapy, none were found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen and have been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogeneous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy, and international collaboration is important.

  18. Targeting embryonic signaling pathways in cancer therapy.

    Science.gov (United States)

    Harris, Pamela Jo; Speranza, Giovanna; Dansky Ullmann, Claudio

    2012-01-01

    The embryonic signaling pathways (ESP), Hedgehog, Notch and Wnt, are critical for the regulation of normal stem cells and cellular development processes. They are also activated in the majority of cancers. ESP are operational in putative cancer stem cells (CSC), which drive initial tumorigenesis and sustain cancer progression and recurrence in non-CSC bulk subpopulations. ESP represent novel therapeutic targets. A variety of inhibitors and targeting strategies are being developed. This review discusses the rationale for targeting ESP for cancer treatment, as well as specific inhibitors under development; mainly focusing on those approaching clinical use and the challenges that lie ahead. The data sources utilized are several database search engines (PubMed, Google, Clinicaltrials.gov), and the authors' involvement in the field. CSC research is rapidly evolving. Expectations regarding their therapeutic targeting are rising quickly. Further definition of what constitutes a true CSC, proper validation of CSC markers, a better understanding of cross-talk among ESP and other pathways, and interactions with tumor non-CSC and the tumor microenvironment are needed. The appropriate patient population, the right clinical setting and combination strategies to test these therapies, as well as the proper pharmacodynamic markers to measure, need to be further established.

  19. Targeted Radionuclide Therapy: An Evolution Toward Precision Cancer Treatment.

    Science.gov (United States)

    Jadvar, Hossein

    2017-08-01

    This article reviews recent developments in targeted radionuclide therapy (TRT) approaches directed to malignant liver lesions, bone metastases, neuroendocrine tumors, and castrate-resistant metastatic prostate cancer and discusses challenges and opportunities in this field. TRT has been employed since the first radioiodine thyroid treatment almost 75 years ago. Progress in the understanding of the complex underlying biology of cancer and advances in radiochemistry science, multimodal imaging techniques including the concept of "see and treat" within the framework of theranostics, and universal traction with the notion of precision medicine have all contributed to a resurgence of TRT.

  20. Targeting Gallium to Cancer Cells through the Folate Receptor

    OpenAIRE

    Nerissa Viola-Villegas; Anthony Vortherms; Robert P. Doyle

    2008-01-01

    The development of gallium(III) compounds as anti-cancer agents for both treatment and diagnosis is a rapidly developing field of research. Problems remain in exploring the full potential of gallium(III) as a safe and successful therapeutic agent or as an imaging agent. One of the major issues is that gallium(III) compounds have little tropism for cancer cells. We have combined the targeting properties of folic acid (FA) with long chain liquid polymer poly(ethylene glycol) (PEG) 'spacers’. Th...

  1. The addition of a sagittal image fusion improves the prostate cancer detection in a sensor-based MRI /ultrasound fusion guided targeted biopsy.

    Science.gov (United States)

    Günzel, Karsten; Cash, Hannes; Buckendahl, John; Königbauer, Maximilian; Asbach, Patrick; Haas, Matthias; Neymeyer, Jörg; Hinz, Stefan; Miller, Kurt; Kempkensteffen, Carsten

    2017-01-13

    To explore the diagnostic benefit of an additional image fusion of the sagittal plane in addition to the standard axial image fusion, using a sensor-based MRI/US fusion platform. During July 2013 and September 2015, 251 patients with at least one suspicious lesion on mpMRI (rated by PI-RADS) were included into the analysis. All patients underwent MRI/US targeted biopsy (TB) in combination with a 10 core systematic prostate biopsy (SB). All biopsies were performed on a sensor-based fusion system. Group A included 162 men who received TB by an axial MRI/US image fusion. Group B comprised 89 men in whom the TB was performed with an additional sagittal image fusion. The median age in group A was 67 years (IQR 61-72) and in group B 68 years (IQR 60-71). The median PSA level in group A was 8.10 ng/ml (IQR 6.05-14) and in group B 8.59 ng/ml (IQR 5.65-12.32). In group A the proportion of patients with a suspicious digital rectal examination (DRE) (14 vs. 29%, p = 0.007) and the proportion of primary biopsies (33 vs 46%, p = 0.046) were significantly lower. The rate of PI-RADS 3 lesions were overrepresented in group A compared to group B (19 vs. 9%; p = 0.044). Classified according to PI-RADS 3, 4 and 5, the detection rates of TB were 42, 48, 75% in group A and 25, 74, 90% in group B. The rate of PCa with a Gleason score ≥7 missed by TB was 33% (18 cases) in group A and 9% (5 cases) in group B; p-value 0.072. An explorative multivariate binary logistic regression analysis revealed that PI-RADS, a suspicious DRE and performing an additional sagittal image fusion were significant predictors for PCa detection in TB. 9 PCa were only detected by TB with sagittal fusion (sTB) and sTB identified 10 additional clinically significant PCa (Gleason ≥7). Performing an additional sagittal image fusion besides the standard axial fusion appears to improve the accuracy of the sensor-based MRI/US fusion platform.

  2. Therapeutic targeting of cancer stem cells

    Directory of Open Access Journals (Sweden)

    Marcello eMaugeri-Saccà

    2011-06-01

    Full Text Available Recent breakthroughs in translational oncology are opening new perspectives for the treatment of cancer. The advent of targeted therapies has provided the proof-of-concept to selectively turn-off deregulated oncogenic proteins, while the identification and validation of predictive biomarkers of response has allowed to improve, at least in some cases, their performance. Moreover, a subpopulation of tumor-propagating cells has been identified from many solid and hematological tumors. These cells share functional properties of normal stem cells, and are commonly referred to as cancer stem cells (CSCs. It is emerging that CSCs are defended against broadly-used anticancer agents by means of different, partly interconnected, mechanisms. However, CSCs rely on specific pathways involved in self-renewal that can be pharmacologically antagonized by experimental molecular targeted agents, some of which have recently entered early phases of clinical development. Here, we discuss the spectrum of pharmacological strategies under clinical or preclinical development for CSCs targeting.

  3. Targeting deregulated epigenetic control in cancer.

    Science.gov (United States)

    Zaidi, Sayyed K; Van Wijnen, Andre J; Lian, Jane B; Stein, Janet L; Stein, Gary S

    2013-11-01

    Cancer is a multifaceted disease that involves acquisition of genetic mutations, deletions, and amplifications as well as deregulation of epigenetic mechanisms that fine-tune gene regulation. Key epigenetic mechanisms that include histone modifications, DNA methylation, and non-coding RNA-mediated gene silencing are often deregulated in a variety of cancers. Subnuclear localization of key proteins in the interphase nucleus and bookmarking of genes by lineage commitment factors in mitosis-a new dimension to epigenetic control of fundamental biological processes-is also modified in cancer. In this review, we discuss the various aspects of epigenetic control that are operative in a variety of cancers and their potential for risk assessment, early detection, targeted therapy, and personalized medicine. Copyright © 2013 Wiley Periodicals, Inc.

  4. Prostate-specific Antigen Parameters and Prostate Health Index Enhance Prostate Cancer Prediction With the In-bore 3-T Magnetic Resonance Imaging-guided Transrectal Targeted Prostate Biopsy After Negative 12-Core Biopsy.

    Science.gov (United States)

    Friedl, Alexander; Stangl, Kathrin; Bauer, Wilhelm; Kivaranovic, Danijel; Schneeweiss, Jenifer; Susani, Martin; Hruby, Stephan; Lusuardi, Lukas; Lomoschitz, Fritz; Eisenhuber-Stadler, Edith; Schima, Wolfgang; Brössner, Clemens

    2017-12-01

    To assess prostate cancer (PCa) detection and prediction by combining the in-bore magnetic resonance imaging-guided transrectal targeted prostate biopsy (MRGB) with prostate-specific antigen (PSA) parameters and the Prostate Health Index (PHI) in case of negative 12-core standard biopsy. A total of 112 men (2014-2016) underwent 3-T multiparametric magnetic resonance imaging and subsequent MRGB of Prostate Imaging-Reporting and Data System (PI-RADS) lesions 3-5. Ancillary PSA parameters (PSA ratio [%fPSA] and PSA density [PSAD]) and the PHI and PHI density (PHID) were recorded. With these parameters in combination with MRGB, PCa prediction was calculated. The most common lesions biopsied were PI-RADS 4 (66%), located in the peripheral zone (64%), in the middle (58%) and anterior (65%) sections of the prostate, and 13 mm (IQR 10-15) in size. PCa was found in 62 (55%) patients (28% Gleason score ≥7). PSAD (0.15 vs 0.21; P = .0051), %fPSA (16 vs 13; P = .0191), PHI (45 vs 69; P PI-RADS 3-5 lesions. By considering PHI and PHID, 82% and 62% of unnecessary biopsies could have been avoided, failing to detect 31% and 16% of cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. In vitro evaluation of the L-peptide modified magnetic lipid nanoparticles as targeted magnetic resonance imaging contrast agent for the nasopharyngeal cancer.

    Science.gov (United States)

    Chen, Yung-Chu; Min, Chia-Na; Wu, Han-Chung; Lin, Chin-Tarng; Hsieh, Wen-Yuan

    2013-11-01

    The purpose of this study was to analyze the encapsulation of superparamagnetic iron oxide nanoparticles (SPION) by the lipid nanoparticle conjugated with the 12-mer peptides (RLLDTNRPLLPY, L-peptide), and the delivery of this complex into living cells. The lipid nanoparticles employed in this work were highly hydrophilic, stable, and contained poly(ethylene-glycol) for conjugation to the bioactive L-peptide. The particle sizes of two different magnetic lipid nanoparticles, L-peptide modified (LML) and non-L-peptide modified (ML), were both around 170 nm with a narrow range of size disparity. The transversal relaxivity, r2, for both LML and ML nanoparticles were found to be significantly higher than the longitudinal relaxivity r1 (r2/r1 > 20). The in vitro tumor cell targeting efficacy of the LML nanoparticles were evaluated and compared to the ML nanoparticles, upon observing cellular uptake of magnetic lipid nanoparticles by the nasopharyngeal carcinoma cells, which express cell surface specific protein for the L-peptide binding revealed. In the Prussian blue staining experiment, cells incubated with LML nanoparticles indicated much higher intracellular iron density than cells incubated with only the ML and SPION nanoparticles. In addition, the MTT assay showed the negligible cell cytotoxicity for LML, ML and SPION nanoparticles. The MR imaging studies demonstrate the better T2-weighted images for the LML-nanoparticle-loaded nasopharyngeal carcinoma cells than the ML- and SPION-loaded cells.

  6. Targeted Therapy in Nonmelanoma Skin Cancers

    Directory of Open Access Journals (Sweden)

    Giulia Spallone

    2011-05-01

    Full Text Available Nonmelanoma skin cancer (NMSC is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC, representing around 75% of NMSC and Squamous Cell Carcinomas (SCC. The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC.

  7. Targeting DNA Replication Stress for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-08-01

    Full Text Available The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress.

  8. Targeted Therapy in Nonmelanoma Skin Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Spallone, Giulia; Botti, Elisabetta; Costanzo, Antonio, E-mail: antonio.costanzo@uniroma2.it [Department of Dermatology, University of Rome “Tor Vergata”, Via Montpellier 1, 00199, Rome (Italy)

    2011-05-03

    Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC.

  9. Radionuclide carriers for targeting of cancer

    Directory of Open Access Journals (Sweden)

    Stavroula Sofou

    2008-06-01

    Full Text Available Stavroula SofouLaboratory for Drug Delivery Systems, Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic University, Brooklyn, NY, USAAbstract: This review describes strategies for the delivery of therapeutic radionuclides to tumor sites. Therapeutic approaches are summarized in terms of tumor location in the body, and tumor morphology. These determine the radionuclides of choice for suggested targeting ligands, and the type of delivery carriers. This review is not exhaustive in examples of radionuclide carriers for targeted cancer therapy. Our purpose is two-fold: to give an integrated picture of the general strategies and molecular constructs currently explored for the delivery of therapeutic radionuclides, and to identify challenges that need to be addressed. Internal radiotherapies for targeting of cancer are at a very exciting and creative stage. It is expected that the current emphasis on multidisciplinary approaches for exploring such therapeutic directions should enable internal radiotherapy to reach its full potential.Keywords: cancer radiotherapy, targeted radiotherapy, radiotherapy of micrometastases, radiotherapy of solid tumors, radiotherapy of tumor vasculature

  10. Targeting neuroendocrine differentiation for prostate cancer radiosensitization

    Science.gov (United States)

    2017-12-01

    progression. Prostate, 2007. 67(7): p. 764-73. 17. Deeble, P.D., et al., Interleukin-6- and cyclic AMP -mediated signaling potentiates neuroendocrine...intracellular cyclic AMP . Proc Natl Acad Sci U S A, 1994. 91(12): p. 5330-4. 25. Amorino, G.P. and S.J. Parsons, Neuroendocrine cells in prostate cancer...Aggarwal S, Kim SW, Ryu SH, Chung WC and Koo JS. Growth suppression of lung cancer cells by targeting cyclic AMP response ele- ment-binding protein

  11. Physics and imaging for targeting of oligometastases.

    Science.gov (United States)

    Yin, Fang-Fang; Das, Shiva; Kirkpatrick, John; Oldham, Mark; Wang, Zhiheng; Zhou, Su-Min

    2006-04-01

    Oligometastases refer to metastases that are limited in number and location and are amenable to regional treatment. The majority of these metastases appear in the brain, lung, liver, and bone. Although the focus of interest in the past within radiation oncology has been on the treatment of intracranial metastases, there has been growing interest in extracranial sites such as the liver and lung. This is largely because of the rapid development of targeting techniques for oligometastases such as intensity-modulated and image-guided radiation therapy, which has made it possible to deliver single or a few fractions of high-dose radiation treatments, highly conformal to the target. The clinical decision to use radiation to treat oligometastases is based on both radiobiological and physics considerations. The radiobiological considerations involve improvement of treatment schema for time, dose, and volume. Areas of interests are hypofractionation, tumor and normal tissue tolerance, and hypoxia. The physics considerations for oligometastases treatment are focused mainly on ensuring treatment accuracy and precision. This article discusses the physics and imaging aspects involved in each step of the radiation treatment process for oligometastases, including target definition, treatment simulation, treatment planning, pretreatment target localization, radiation delivery, treatment verification, and treatment evaluation.

  12. Astrophysical targets of the Fresnel diffractive imager

    Science.gov (United States)

    Koechlin, L.; Deba, P.; Raksasataya, T.

    2017-11-01

    The Fresnel Diffractive imager is an innovative concept of distributed space telescope, for high resolution (milli arc-seconds) spectro-imaging in the IR, visible and UV domains. This paper presents its optical principle and the science that can be done on potential astrophysical targets. The novelty lies in the primary optics: a binary Fresnel array, akin to a binary Fresnel zone plate. The main interest of this approach is the relaxed manufacturing and positioning constraints. While having the resolution and imaging capabilities of lens or mirrors of equivalent size, no optical material is involved in the focusing process: just vacuum. A Fresnel array consists of millions void subapertures punched into a large and thin opaque membrane, that focus light by diffraction into a compact and highly contrasted image. The positioning law of the aperture edges drives the image quality and contrast. This optical concept allows larger and lighter apertures than solid state optics, aiming to high angular resolution and high dynamic range imaging, in particular for UV applications. Diffraction focusing implies very long focal distances, up to dozens of kilometers, which requires at least a two-vessel formation flying in space. The first spacecraft, "the Fresnel Array spacecraft", holds the large punched foil: the Fresnel Array. The second, the "Receiver spacecraft" holds the field optics and focal instrumentation. A chromatism correction feature enables moderately large (20%) relative wavebands, and fields of a few to a dozen arc seconds. This Fresnel imager is adapted to high contrast stellar environments: dust disks, close companions and (we hope) exoplanets. Specific to the particular grid-like pattern of the primary focusing zone plate, is the very high dynamic range achieved in the images, in the case of compact objects. Large stellar photospheres may also be mapped with Fresnel arrays of a few meters opertaing in the UV. Larger and more complex fields can be imaged with

  13. Cancer nanomedicine: from drug delivery to imaging.

    Science.gov (United States)

    Chow, Edward Kai-Hua; Ho, Dean

    2013-12-18

    Nanotechnology-based chemotherapeutics and imaging agents represent a new era of "cancer nanomedicine" working to deliver versatile payloads with favorable pharmacokinetics and capitalize on molecular and cellular targeting for enhanced specificity, efficacy, and safety. Despite the versatility of many nanomedicine-based platforms, translating new drug or imaging agents to the clinic is costly and often hampered by regulatory hurdles. Therefore, translating cancer nanomedicine may largely be application-defined, where materials are adapted only toward specific indications where their properties confer unique advantages. This strategy may also realize therapies that can optimize clinical impact through combinatorial nanomedicine. In this review, we discuss how particular materials lend themselves to specific applications, the progress to date in clinical translation of nanomedicine, and promising approaches that may catalyze clinical acceptance of nano.

  14. Clinical photoacoustic imaging of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Valluru, Keerthi S.; Willmann, Juergen K. [Dept. of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford (United States)

    2016-08-15

    Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented.

  15. Molecularly targeted drugs for metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Cheng YD

    2013-11-01

    Full Text Available Ying-dong Cheng, Hua Yang, Guo-qing Chen, Zhi-cao Zhang Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China Abstract: The survival rate of patients with metastatic colorectal cancer (mCRC has significantly improved with applications of molecularly targeted drugs, such as bevacizumab, and led to a substantial improvement in the overall survival rate. These drugs are capable of specifically targeting the inherent abnormal pathways in cancer cells, which are potentially less toxic than traditional nonselective chemotherapeutics. In this review, the recent clinical information about molecularly targeted therapy for mCRC is summarized, with specific focus on several of the US Food and Drug Administration-approved molecularly targeted drugs for the treatment of mCRC in the clinic. Progression-free and overall survival in patients with mCRC was improved greatly by the addition of bevacizumab and/or cetuximab to standard chemotherapy, in either first- or second-line treatment. Aflibercept has been used in combination with folinic acid (leucovorin–fluorouracil–irinotecan (FOLFIRI chemotherapy in mCRC patients and among patients with mCRC with wild-type KRAS, the outcomes were significantly improved by panitumumab in combination with folinic acid (leucovorin–fluorouracil–oxaliplatin (FOLFOX or FOLFIRI. Because of the new preliminary studies, it has been recommended that regorafenib be used with FOLFOX or FOLFIRI as first- or second-line treatment of mCRC chemotherapy. In summary, an era of new opportunities has been opened for treatment of mCRC and/or other malignancies, resulting from the discovery of new selective targeting drugs. Keywords: metastatic colorectal cancer (mCRC, antiangiogenic drug, bevacizumab, aflibercept, regorafenib, cetuximab, panitumumab, clinical trial, molecularly targeted therapy

  16. Therapeutic targeting of cancer cell metabolism.

    Science.gov (United States)

    Dang, Chi V; Hamaker, Max; Sun, Peng; Le, Anne; Gao, Ping

    2011-03-01

    In 1927, Otto Warburg and coworkers reported the increased uptake of glucose and production of lactate by tumors in vivo as compared with normal tissues. This phenomenon, now known as the Warburg effect, was recapitulated in vitro with cancer tissue slices exhibiting excessive lactate production even with adequate oxygen. Warburg's in vivo studies of tumors further suggest that the dependency of tumors in vivo on glucose could be exploited for therapy, because reduction of arterial glucose by half resulted in a four-fold reduction in tumor fermentation. Recent work in cancer metabolism indicates that the Warburg effect or aerobic glycolysis contributes to redox balance and lipid synthesis, but glycolysis is insufficient to sustain a growing and dividing cancer cell. In this regard, glutamine, which contributes its carbons to the tricarboxylic acid (TCA) cycle, has been re-discovered as an essential bioenergetic and anabolic substrate for many cancer cell types. Could alterations in cancer metabolism be exploited for therapy? Here, we address this question by reviewing current concepts of normal metabolism and altered metabolism in cancer cells with specific emphasis on molecular targets involved directly in glycolysis or glutamine metabolism.

  17. Quantitative Image Informatics for Cancer Research (QIICR) | Informatics Technology for Cancer Research (ITCR)

    Science.gov (United States)

    Imaging has enormous untapped potential to improve cancer research through software to extract and process morphometric and functional biomarkers. In the era of non-cytotoxic treatment agents, multi- modality image-guided ablative therapies and rapidly evolving computational resources, quantitative imaging software can be transformative in enabling minimally invasive, objective and reproducible evaluation of cancer treatment response. Post-processing algorithms are integral to high-throughput analysis and fine- grained differentiation of multiple molecular targets.

  18. Targeting Mitosis in Cancer: Emerging Strategies.

    Science.gov (United States)

    Dominguez-Brauer, Carmen; Thu, Kelsie L; Mason, Jacqueline M; Blaser, Heiko; Bray, Mark R; Mak, Tak W

    2015-11-19

    The cell cycle is an evolutionarily conserved process necessary for mammalian cell growth and development. Because cell-cycle aberrations are a hallmark of cancer, this process has been the target of anti-cancer therapeutics for decades. However, despite numerous clinical trials, cell-cycle-targeting agents have generally failed in the clinic. This review briefly examines past cell-cycle-targeted therapeutics and outlines how experience with these agents has provided valuable insight to refine and improve anti-mitotic strategies. An overview of emerging anti-mitotic approaches with promising pre-clinical results is provided, and the concept of exploiting the genomic instability of tumor cells through therapeutic inhibition of mitotic checkpoints is discussed. We believe this strategy has a high likelihood of success given its potential to enhance therapeutic index by targeting tumor-specific vulnerabilities. This reasoning stimulated our development of novel inhibitors targeting the critical regulators of genomic stability and the mitotic checkpoint: AURKA, PLK4, and Mps1/TTK. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Geometrical differences in target volumes based on 18F-fluorodeoxyglucose positron emission tomography/computed tomography and four-dimensional computed tomography maximum intensity projection images of primary thoracic esophageal cancer.

    Science.gov (United States)

    Guo, Y; Li, J; Wang, W; Zhang, Y; Wang, J; Duan, Y; Shang, D; Fu, Z

    2014-01-01

    The objective of the study was to compare geometrical differences of target volumes based on four-dimensional computed tomography (4DCT) maximum intensity projection (MIP) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images of primary thoracic esophageal cancer for radiation treatment. Twenty-one patients with thoracic esophageal cancer sequentially underwent contrast-enhanced three-dimensional computed tomography (3DCT), 4DCT, and 18F-FDG PET/CT thoracic simulation scans during normal free breathing. The internal gross target volume defined as IGTVMIP was obtained by contouring on MIP images. The gross target volumes based on PET/CT images (GTVPET ) were determined with nine different standardized uptake value (SUV) thresholds and manual contouring: SUV≥2.0, 2.5, 3.0, 3.5 (SUVn); ≥20%, 25%, 30%, 35%, 40% of the maximum (percentages of SUVmax, SUVn%). The differences in volume ratio (VR), conformity index (CI), and degree of inclusion (DI) between IGTVMIP and GTVPET were investigated. The mean centroid distance between GTVPET and IGTVMIP ranged from 4.98 mm to 6.53 mm. The VR ranged from 0.37 to 1.34, being significantly (P<0.05) closest to 1 at SUV2.5 (0.94), SUV20% (1.07), or manual contouring (1.10). The mean CI ranged from 0.34 to 0.58, being significantly closest to 1 (P<0.05) at SUV2.0 (0.55), SUV2.5 (0.56), SUV20% (0.56), SUV25% (0.53), or manual contouring (0.58). The mean DI of GTVPET in IGTVMIP ranged from 0.61 to 0.91, and the mean DI of IGTVMIP in GTVPET ranged from 0.34 to 0.86. The SUV threshold setting of SUV2.5, SUV20% or manual contouring yields the best tumor VR and CI with internal-gross target volume contoured on MIP of 4DCT dataset, but 3DPET/CT and 4DCT MIP could not replace each other for motion encompassing target volume delineation for radiation treatment. © 2014 International Society for Diseases of the Esophagus.

  20. Targeting glia for bone cancer pain.

    Science.gov (United States)

    Zhou, Ya-Qun; Liu, Zheng; Liu, Hui-Quan; Liu, Dai-Qiang; Chen, Shu-Ping; Ye, Da-Wei; Tian, Yu-Ke

    2016-11-01

    Bone cancer pain (BCP) remains to be a clinical challenge with limited pharmaceutical interventions. Therefore, novel therapeutic targets for the management of BCP are in desperate need. Recently, a growing body of evidence has suggested that glial cells may play a pivotal role in the pathogenesis of BCP. Areas covered: This review summarizes the recent progress in the understanding of glia in BCP and reveals the potential therapeutic targets in glia for BCP treatment. Expert opinion: Pharmacological interventions inhibiting the activation of glial cells, suppressing glia-derived proinflammatory cytokines, cell surface receptors, and the intracellular signaling pathways may be beneficial for the pain management of advanced cancer patients. However, these pharmacological interventions should not disrupt the normal function of glia cells since they play a vital supportive and protective role in the central nervous system.

  1. Mesoscopic and macroscopic optoacoustic imaging of cancer.

    Science.gov (United States)

    Taruttis, Adrian; van Dam, Gooitzen M; Ntziachristos, Vasilis

    2015-04-15

    Optoacoustic imaging combines the rich contrast of optical methods with the resolution of ultrasound imaging. It can therefore deliver optical visualization of cancer far deeper in tissue than optical microscopy and other conventional optical imaging methods. Technological progress and novel contrast media have resulted in optoacoustic imaging being propagated to basic cancer research and in clinical translation projects. We briefly review recent technological advances, showcase the ability to resolve unique cancer biomarkers based on spectral features at different imaging scales, and highlight the imaging performance achieved in preclinical and clinical imaging applications. . ©2015 American Association for Cancer Research.

  2. Metastasis Targeted Therapies in Renal Cell Cancer

    OpenAIRE

    K. Fehmi Narter; Bora Özveren

    2018-01-01

    Metastatic renal cell cancer is a malignant disease and its treatment has been not been described clearly yet. These patients are generally symptomatic and resistant to current treatment modalities. Radiotherapy, chemotherapy, and hormonal therapy are not curative in many of these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (immunotherapy or targeted molecules), and metastasectomy has been shown to be hopeful in prolonging the survival and improvi...

  3. Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy

    Directory of Open Access Journals (Sweden)

    Xiang-Hong Peng

    2008-10-01

    Full Text Available Xiang-Hong Peng1,4, Ximei Qian2,4, Hui Mao3,4, Andrew Y Wang5, Zhuo (Georgia Chen1,4, Shuming Nie2,4, Dong M Shin1,4*1Department of Medical Oncology/Hematology; 2Department of Biomedical Engineering; 3Department of Radiology; 4Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; 5Ocean Nanotech, LLC, Fayetteville, AR, USAAbstract: Magnetic iron oxide (IO nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo. IO nanoparticles have a large surface area and can be engineered to provide a large number of functional groups for cross-linking to tumor-targeting ligands such as monoclonal antibodies, peptides, or small molecules for diagnostic imaging or delivery of therapeutic agents. IO nanoparticles possess unique paramagnetic properties, which generate significant susceptibility effects resulting in strong T2 and T*2 contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI, which is widely used for clinical oncology imaging. We review recent advances in the development of targeted IO nanoparticles for tumor imaging and therapy.Keywords: iron oxide nanoparticles, tumor imaging, MRI, therapy

  4. Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions.

    Science.gov (United States)

    Vernieri, Claudio; Casola, Stefano; Foiani, Marco; Pietrantonio, Filippo; de Braud, Filippo; Longo, Valter

    2016-12-01

    Most tumors display oncogene-driven reprogramming of several metabolic pathways, which are crucial to sustain their growth and proliferation. In recent years, both dietary and pharmacologic approaches that target deregulated tumor metabolism are beginning to be considered for clinical applications. Dietary interventions exploit the ability of nutrient-restricted conditions to exert broad biological effects, protecting normal cells, organs, and systems, while sensitizing a wide variety of cancer cells to cytotoxic therapies. On the other hand, drugs targeting enzymes or metabolites of crucial metabolic pathways can be highly specific and effective, but must be matched with a responsive tumor, which might rapidly adapt. In this review, we illustrate how dietary and pharmacologic therapies differ in their effect on tumor growth, proliferation, and metabolism and discuss the available preclinical and clinical evidence in favor of or against each of them. We also indicate, when appropriate, how to optimize future investigations on metabolic therapies on the basis of tumor- and patient-related characteristics. To our knowledge, this is the first review article that comprehensively analyzes the preclinical and preliminary clinical experimental foundations of both dietary and pharmacologic metabolic interventions in cancer therapy. Among several promising therapies, we propose treatment personalization on the basis of tumor genetics, tumor metabolism, and patient systemic metabolism.Cancer Discov; 6(12); 1315-33. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Sonophore labeled RGD: a targeted contrast agent for optoacoustic imaging.

    Science.gov (United States)

    Haedicke, Katja; Brand, Christian; Omar, Murad; Ntziachristos, Vasilis; Reiner, Thomas; Grimm, Jan

    2017-06-01

    Optoacoustic imaging is a rapidly expanding field for the diagnosis, characterization, and treatment evaluation of cancer. However, the availability of tumor specific exogenous contrast agents is still limited. Here, we report on a small targeted contrast agent for optoacoustic imaging using a black hole quencher ® (BHQ) dye. The sonophore BHQ-1 exhibited strong, concentration-dependent, optoacoustic signals in phantoms, demonstrating its ideal suitability for optoacoustic imaging. After labeling BHQ-1 with cyclic RGD-peptide, BHQ-1-cRGD specifically bound to α v β 3 -integrin expressing glioblastoma cell spheroids in vitro . The excellent optoacoustic properties of BHQ-1-cRGD could furthermore be proven in vivo . Together with this emerging imaging modality, our sonophore labeled small peptide probe offers new possibilities for non-invasive detection of molecular structures with high resolution in vivo and furthers the specificity of optoacoustic imaging. Ultimately, the discovery of tailor-made sonophores might offer new avenues for various molecular optoacoustic imaging applications, similar to what we see with fluorescence imaging.

  6. Sonophore labeled RGD: a targeted contrast agent for optoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Katja Haedicke

    2017-06-01

    Full Text Available Optoacoustic imaging is a rapidly expanding field for the diagnosis, characterization, and treatment evaluation of cancer. However, the availability of tumor specific exogenous contrast agents is still limited. Here, we report on a small targeted contrast agent for optoacoustic imaging using a black hole quencher® (BHQ dye. The sonophore BHQ-1 exhibited strong, concentration-dependent, optoacoustic signals in phantoms, demonstrating its ideal suitability for optoacoustic imaging. After labeling BHQ-1 with cyclic RGD-peptide, BHQ-1-cRGD specifically bound to αvβ3-integrin expressing glioblastoma cell spheroids in vitro. The excellent optoacoustic properties of BHQ-1-cRGD could furthermore be proven in vivo. Together with this emerging imaging modality, our sonophore labeled small peptide probe offers new possibilities for non-invasive detection of molecular structures with high resolution in vivo and furthers the specificity of optoacoustic imaging. Ultimately, the discovery of tailor-made sonophores might offer new avenues for various molecular optoacoustic imaging applications, similar to what we see with fluorescence imaging.

  7. Breast Cancer Survivorship Care: Targeting a Colorectal Cancer Education Intervention

    Directory of Open Access Journals (Sweden)

    Sherri G. Homan

    2015-08-01

    Full Text Available Breast cancer survivors are at risk of developing a second primary cancer. Colorectal cancer (CRC is one of the leading second primary cancers, and it is often preventable. We developed a multi-component educational tool to inform and encourage women breast cancer survivors to engage in CRC screening. To assess the strengths and weakness of the tool and to improve the relevancy to the target audience, we convened four focus groups of women breast cancer survivors in Missouri. We also assessed the potential impact of the tool on the knowledge, attitudes, and beliefs regarding CRC and collected information on the barriers to CRC screening through pre- and post-focus groups’ questionnaires. A total of 43 women breast cancer survivors participated and provided very valuable suggestions on design and content to update the tool. Through the process and comparing pre- and post-focus group assessments, a significantly higher proportion of breast cancer survivors strongly agreed or agreed that CRC is preventable (78.6% vs. 96.9%, p = 0.02 and became aware that they were at a slightly increased risk for CRC (18.6% vs. 51.7%, p = 0.003. The most cited barrier was the complexity of preparation for colonoscopy.

  8. Targeted Therapeutic Nanoparticles: An Immense Promise to Fight against Cancer

    Directory of Open Access Journals (Sweden)

    Sheikh Tasnim Jahan

    2017-01-01

    Full Text Available In nanomedicine, targeted therapeutic nanoparticle (NP is a virtual outcome of nanotechnology taking the advantage of cancer propagation pattern. Tying up all elements such as therapeutic or imaging agent, targeting ligand, and cross-linking agent with the NPs is the key concept to deliver the payload selectively where it intends to reach. The microenvironment of tumor tissues in lymphatic vessels can also help targeted NPs to achieve their anticipated accumulation depending on the formulation objectives. This review accumulates the application of poly(lactic-co-glycolic acid (PLGA and polyethylene glycol (PEG based NP systems, with a specific perspective in cancer. Nowadays, PLGA, PEG, or their combinations are the mostly used polymers to serve the purpose of targeted therapeutic NPs. Their unique physicochemical properties along with their biological activities are also discussed. Depending on the biological effects from parameters associated with existing NPs, several advantages and limitations have been explored in teaming up all the essential facts to give birth to targeted therapeutic NPs. Therefore, the current article will provide a comprehensive review of various approaches to fabricate a targeted system to achieve appropriate physicochemical properties. Based on such findings, researchers can realize the benefits and challenges for the next generation of delivery systems.

  9. Glypican-3 Targeting of Liver Cancer Cells Using Multifunctional Nanoparticles

    Directory of Open Access Journals (Sweden)

    James O. Park

    2011-01-01

    Full Text Available Imaging is essential in accurately detecting, staging, and treating primary liver cancer (hepatocellular carcinoma [HCC], one of the most prevalent and lethal malignancies. We developed a novel multifunctional nanoparticle (NP specifically targeting glypican-3 (GPC3, a proteoglycan implicated in promotion of cell growth that is overexpressed in most HCCs. Quantitative real-time polymerase chain reaction was performed to confirm the differential GPC3 expression in two human HCC cells, Hep G2 (high and HLF (negligible. These cells were treated with biotin-conjugated GPC3 monoclonal antibody (αGPC3 and subsequently targeted using superparamagnetic iron oxide NPs conjugated to streptavidin and Alexa Fluor 647. Flow cytometry demonstrated that only GPC3-expressing Hep G2 cells were specifically targeted using this αGPC3-NP conjugate (fourfold mean fluorescence over nontargeted NP, and magnetic resonance imaging (MRI experiments showed similar findings (threefold R2 relaxivity. Confocal fluorescence microscopy localized the αGPC3 NPs only to the cell surface of GPC3-expressing Hep G2 cells. Further characterization of this construct demonstrated a negatively charged, monodisperse, 50 nm NP, ideally suited for tumor targeting. This GPC3-specific NP system, with dual-modality imaging capability, may enhance pretreatment MRI, enable refined intraoperative HCC visualization by near-infrared fluorescence, and be potentially used as a carrier for delivery of tumor-targeted therapies, improving patient outcomes.

  10. Asymmetric Cationic Porphyrin as a New G-Quadruplex Probe with Wash-Free Cancer-Targeted Imaging Ability Under Acidic Microenvironments.

    Science.gov (United States)

    Zhang, Ran; Cheng, Meng; Zhang, Li-Ming; Zhu, Li-Na; Kong, De-Ming

    2018-04-16

    Porphyrins are promising candidates for nucleic acid G-quadruplex-specific optical recognition. We previously demonstrated that G-quadruplex recognition specificity of porphyrins could be improved by introducing bulky side arm substituents, but the enhanced protonation tendency limits their applications in some cases, such as under acidic conditions. Here, we demonstrated that the protonation tendency of porphyrin derivatives could be efficiently overcome by increasing molecular asymmetry. To validate this, an asymmetric, water-soluble, cationic porphyrin FA-TMPipEOPP (5-{4-[2-[[(2 E)-3-[3-methoxy-4-[2-(1-methyl-1-piperidinyl)ethoxy]phenyl]-1-oxo-2-propenyl]oxy]ethoxy]phenyl},10,15,20-tri{4-[2-(1-methyl-1-piperidinyl)ethoxy]-phenyl}porphyrin) was synthesized by introducing a ferulic acid (FA) unit at one side arm, and its structure was well-characterized. Unlike its symmetric counterpart TMPipEOPP that has a tendency to protonate under acidic conditions, FA-TMPipEOPP remained in the unprotonated monomeric form under the pH range of 2.0-8.0. Correspondingly, FA-TMPipEOPP showed better G-quadruplex recognition specificity than TMPipEOPP and thus might be used as a specific optical probe for colorimetric and fluorescent recognition of G-quadruplexes under acidic conditions. The feasibility was demonstrated by two proof-of-concept studies: probing structural competition between G-quadruplexes and duplexes and label-free and wash-free cancer cell-targeted bioimaging under an acidic tumor microenvironment. As G-quadruplex optical probes, FA-TMPipEOPP works well under acidic conditions, whereas TMPipEOPP works well under neutral conditions. This finding provides useful information for G-quadruplex probe research. That is, porphyrin-based G-quadruplex probes suitable for different pH conditions might be obtained by adjusting the molecular symmetry.

  11. Tumor-targeted nanomedicines for cancer theranostics

    Science.gov (United States)

    Lammers, Twan; Shi, Yang

    2017-01-01

    Chemotherapeutic drugs have multiple drawbacks, including severe side effects and suboptimal therapeutic efficacy. Nanomedicines assist in improving the biodistribution and the target accumulation of chemotherapeutic drugs, and are therefore able to enhance the balance between efficacy and toxicity. Multiple different types of nanomedicines have been evaluated over the years, including liposomes, polymer-drug conjugates and polymeric micelles, which rely on strategies such as passive targeting, active targeting and triggered release for improved tumor-directed drug delivery. Based on the notion that tumors and metastases are highly heterogeneous, it is important to integrate imaging properties in nanomedicine formulations in order to enable non-invasive and quantitative assessment of targeting efficiency. By allowing for patient pre-selection, such next generation nanotheranostics are useful for facilitating clinical translation and personalizing nanomedicine treatments. PMID:27865762

  12. Targeted therapy for biliary tract cancers.

    Science.gov (United States)

    Faris, Jason E; Zhu, Andrew X

    2012-07-01

    Biliary tract cancers (BTCs) are a heterogeneous group of malignancies, with a historically poor prognosis as a whole. Until recently, the development of effective therapeutics was hampered by the relatively low incidence, heterogeneity in patients and tumors, and correspondingly poor clinical trial enrollments. With the publication of the landmark phase III ABC-02 trial demonstrating the superiority of gemcitabine and cisplatin combination chemotherapy, the landscape changed for the development of new agents. Despite this progress, there are currently no approved targeted agents for BTC. This review will focus on recent developments in targeted therapeutics, directed against several key signaling pathways in BTC, including epidermal growth factor receptor, angiogenesis, and the mitogen-activated protein kinase pathway. Data from recent phase I and II trials will be discussed, along with a preview of upcoming trials involving targeted therapies.

  13. Mesoscopic and Macroscopic Optoacoustic Imaging of Cancer

    NARCIS (Netherlands)

    Taruttis, Adrian; van Dam, Gooitzen M.; Ntziachristos, Vasilis

    2015-01-01

    Optoacoustic imaging combines the rich contrast of optical methods with the resolution of ultrasound imaging. It can therefore deliver optical visualization of cancer far deeper in tissue than optical microscopy and other conventional optical imaging methods. Technological progress and novel

  14. Implementing MRI-based target delineation for cervical cancer treatment within a rapid workflow environment for image-guided brachytherapy: A practical approach for centers without in-room MRI.

    Science.gov (United States)

    Trifiletti, Daniel M; Libby, Bruce; Feuerlein, Sebastian; Kim, Taeho; Garda, Allison; Watkins, W Tyler; Erickson, Sarah; Ornan, Afshan; Showalter, Timothy N

    2015-01-01

    Magnetic resonance imaging (MRI)-based intracavitary brachytherapy offers several advantages over computed tomography (CT)-based brachytherapy, but many centers are unable to offer it at the time of brachytherapy because of logistic and/or financial considerations. We have implemented a method of integrating MRI into a CT-guided, high-dose-rate intracavitary brachytherapy workflow in clinics that do not have immediately available MRI capability. At our institution, patients receiving high-dose-rate intracavitary brachytherapy as a component of the definitive treatment of cervical cancer have a Smit sleeve placed during the first brachytherapy fraction in a dedicated suite with in-room CT-on-rails. After the first fraction of brachytherapy, an MRI is obtained with the Smit sleeve, but no applicator, in place. For each subsequent fraction, CT scans are coregistered to the MRI scan by the Smit sleeve. The gross target volume is defined by MRI and overlaid on the CT images for each brachytherapy treatment for dose optimization. This MRI-integrated workflow adds workflow is a feasible compromise to preserve an efficient workflow while integrating MRI target delineation, and it provides many of the advantages of both MRI- and CT-based brachytherapy. The future collection and analysis of clinical data will serve to compare the proposed approach to non-MRI containing techniques. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  15. Noninvasive theranostic imaging of HSV-TK/GCV suicide gene therapy in liver cancer by folate-targeted quantum dot-based liposomes

    NARCIS (Netherlands)

    Shao, D.; Li, J.; Pan, Y.; Zhang, X.; Zheng, X.; Wang, Z.; Zhang, M.; Zhang, H.; Chen, L.

    2015-01-01

    Theranostics is emerging as a popular strategy for cancer therapy; thanks to the development of nano-technology. In this work, we have combined an HSV-TK/GCV suicide gene system and near-infrared quantum dots, as the former is quite effective in liver cancer treatment and the latter facilitates

  16. Apoptosis and Molecular Targeting Therapy in Cancer

    Science.gov (United States)

    Hassan, Mohamed; Watari, Hidemichi; AbuAlmaaty, Ali; Ohba, Yusuke; Sakuragi, Noriaki

    2014-01-01

    Apoptosis is the programmed cell death which maintains the healthy survival/death balance in metazoan cells. Defect in apoptosis can cause cancer or autoimmunity, while enhanced apoptosis may cause degenerative diseases. The apoptotic signals contribute into safeguarding the genomic integrity while defective apoptosis may promote carcinogenesis. The apoptotic signals are complicated and they are regulated at several levels. The signals of carcinogenesis modulate the central control points of the apoptotic pathways, including inhibitor of apoptosis (IAP) proteins and FLICE-inhibitory protein (c-FLIP). The tumor cells may use some of several molecular mechanisms to suppress apoptosis and acquire resistance to apoptotic agents, for example, by the expression of antiapoptotic proteins such as Bcl-2 or by the downregulation or mutation of proapoptotic proteins such as BAX. In this review, we provide the main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells. We discuss how carcinogenesis could be developed via defective apoptotic pathways or their convergence. We listed some molecules which could be targeted to stimulate apoptosis in different cancers. Together, we briefly discuss the development of some promising cancer treatment strategies which target apoptotic inhibitors including Bcl-2 family proteins, IAPs, and c-FLIP for apoptosis induction. PMID:25013758

  17. Targeted therapy for esophagogastric cancers: a review

    Directory of Open Access Journals (Sweden)

    Khattak MA

    2012-05-01

    Full Text Available Muhammad A Khattak,1 Hilary L Martin,2 Christos S Karapetis1,31Flinders Medical Centre, Adelaide, South Australia; 2Calvary Hospital, Adelaide, SA, Australia; 3Flinders University, Adelaide, SA, AustraliaAbstract: The incidence of esophagogastric cancers is increasing rapidly in the Western population. Despite better understanding of the biology and intense research in the treatment of these cancers, the long-term survival remains poor both in the locally advanced and metastatic settings. The addition of combined modality strategies has resulted in modest improvement in 5-year survival rates. A number of biologic agents targeting epidermal-derived growth factor receptor, vascular endothelial derived growth factor and its receptor, and mammalian target of rapamycin (mTOR are being currently evaluated in Phase II and III clinical trials. Some of these, like trastuzumab, cetuximab, and bevacizumab, have shown promising results. This review provides a brief overview of the recent developments in biologic agents for the treatment of esophagogastric cancers.Keywords: adenocarcinoma, squamous cell carcinoma, VEGF, trastuzumab, Her2- positive EGC

  18. Glycomic Approaches for the Discovery of Targets in Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Stefan eMereiter

    2016-03-01

    Full Text Available Gastrointestinal (GI cancer is the most common group of malignancies and many of its types are among the most deadly. Various glycoconjugates have been used in clinical practice as serum biomarker for several GI tumors, however with limited diagnose application. Despite the good accessibility by endoscopy of many GI organs, the lack of reliable serum biomarkers often leads to late diagnosis of malignancy and consequently low 5-year survival rates. Recent advances in analytical techniques have provided novel glycoproteomic and glycomic data and generated functional information and putative biomarker targets in oncology. Glycosylation alterations have been demonstrated in a series of glycoconjugates (glycoproteins, proteoglycans and glycosphingolipids that are involved in cancer cell adhesion, signaling, invasion and metastasis formation. In this review, we present an overview on the major glycosylation alterations in GI cancer and the current serological biomarkers used in the clinical oncology setting. We further describe recent glycomic studies in GI cancer, namely gastric, colorectal and pancreatic cancer. Moreover, we discuss the role of glycosylation as a modulator of the function of several key players in cancer cell biology. Finally, we address several state-of-the-art techniques currently applied in this field, such as glycomic and glycoproteomic analyses, the application of glycoengineered cell line models, microarray and proximity ligation assay, as well as imaging mass spectrometry and provide an outlook to future perspectives and clinical applications.

  19. PET imaging in breast cancer

    International Nuclear Information System (INIS)

    Bombardieri, E.; Crippa, F.

    2001-01-01

    The basis of tumour imaging with PET is a specific uptake mechanism of positron emitting radiopharmaceuticals. Among the potential tracers for breast cancer (fluorodeoxyglucose, methionine, tyrosine, fluoro-estradiol, nor-progesterone), 2-deoxy-2-fluoro-D-glucose labelled with fluorine (FDG) is the most widely used radiopharmaceutical because breast cancer is particularly avid of FDG and 18 F has the advantages of the a relatively long physical half-life. Mammography is the first choice examination in studying breast masses, due to its very good performances, an excellent compliance and the best value regarding the cost/effectiveness aspects. The FDG uptake in tissue correlates with the histological grade and potential aggressiveness of breast cancer and this may have prognostic consequences. Besides the evaluation of breast lesions, FDG-PET shows a great efficacy in staging lymph node involvement prior surgery and this could have a great value in loco-regional staging. Whole body PET provides also information with regard to metastasis localizations both in soft tissue and bone, and plays an important clinical role mainly in detecting recurrent metastatic disease. In fact for its metabolic characteristics PET visualizes regions of enhanced metabolic activity and can complete other imaging modalities based on structural anatomic changes. Even though CT and MRI show superior resolution characteristics, it has been demonstrated that PET provides more accurate information in discriminating between viable tumour, fibrotic scar or necrosis. These statements are coming from the examination of more than 2000 breast cancer detection

  20. Molecular targeted therapy in modern oncology: Imaging assessment of treatment response and toxicities

    Energy Technology Data Exchange (ETDEWEB)

    Krajewski, Katherine M.; Braschi-Amirfarzan, Marta; DiPiro, Pamela J.; Jagannathan, Jyothi P.; Shinagare, Atul B. [Dept. of of Imaging, Dana Farber Cancer Institute, Boston (United States)

    2017-01-15

    Oncology is a rapidly evolving field with a shift toward personalized cancer treatment. The use of therapies targeted to the molecular features of individual tumors and the tumor microenvironment has become much more common. In this review, anti-angiogenic and other molecular targeted therapies are discussed, with a focus on typical and atypical response patterns and imaging manifestations of drug toxicities.

  1. Targeted cancer therapy; nanotechnology approaches for overcoming drug resistance.

    Science.gov (United States)

    Gao, Yan; Shen, Jacson K; Milane, Lara; Hornicek, Francis J; Amiji, Mansoor M; Duan, Zhenfeng

    2015-01-01

    Recent advances in cancer molecular biology have resulted in parallel and unprecedented progress in the development of targeted cancer therapy. Targeted therapy can provide higher efficacy and lower toxicity than conventional chemotherapy for cancer. However, like traditional chemotherapy, molecularly targeted cancer therapy also faces the challenge of drug resistance. Multiple mechanisms are responsible for chemotherapy resistance in tumors, including over-expression of efflux transporters, somatic alterations of drug targets, deregulation of apoptosis, and numerous pharmacokinetic issues. Nanotechnology based approaches are proving to be efficacious in overcoming drug resistance in cancer. Combination of targeted therapies with nanotechnology approaches is a promising strategy to overcome targeted therapy drug resistance in cancer treatment. This review discusses the mechanisms of targeted drug resistance in cancer and discusses nanotechnology approaches to circumvent this resistance.

  2. Integrins as Therapeutic Targets: Successes and Cancers

    Directory of Open Access Journals (Sweden)

    Sabine Raab-Westphal

    2017-08-01

    Full Text Available Integrins are transmembrane receptors that are central to the biology of many human pathologies. Classically mediating cell-extracellular matrix and cell-cell interaction, and with an emerging role as local activators of TGFβ, they influence cancer, fibrosis, thrombosis and inflammation. Their ligand binding and some regulatory sites are extracellular and sensitive to pharmacological intervention, as proven by the clinical success of seven drugs targeting them. The six drugs on the market in 2016 generated revenues of some US$3.5 billion, mainly from inhibitors of α4-series integrins. In this review we examine the current developments in integrin therapeutics, especially in cancer, and comment on the health economic implications of these developments.

  3. Targeting regulatory T cells in cancer.

    LENUS (Irish Health Repository)

    Byrne, William L

    2012-01-31

    Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-kappaB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy.

  4. Rosamines targeting the cancer oxidative phosphorylation pathway.

    Directory of Open Access Journals (Sweden)

    Siang Hui Lim

    Full Text Available Reprogramming of energy metabolism is pivotal to cancer, so mitochondria are potential targets for anticancer therapy. A prior study has demonstrated the anti-proliferative activity of a new class of mitochondria-targeting rosamines. This present study describes in vitro cytotoxicity of second-generation rosamine analogs, their mode of action, and their in vivo efficacies in a tumor allografted mouse model. Here, we showed that these compounds exhibited potent cytotoxicity (average IC50<0.5 µM, inhibited Complex II and ATP synthase activities of the mitochondrial oxidative phosphorylation pathway and induced loss of mitochondrial transmembrane potential. A NCI-60 cell lines screen further indicated that rosamine analogs 4 and 5 exhibited potent antiproliferative effects with Log10GI50 = -7 (GI50 = 0.1 µM and were more effective against a colorectal cancer sub-panel than other cell lines. Preliminary in vivo studies on 4T1 murine breast cancer-bearing female BALB/c mice indicated that treatment with analog 5 in a single dosing of 5 mg/kg or a schedule dosing of 3 mg/kg once every 2 days for 6 times (q2d×6 exhibited only minimal induction of tumor growth delay. Our results suggest that rosamine analogs may be further developed as mitochondrial targeting agents. Without a doubt proper strategies need to be devised to enhance tumor uptake of rosamines, i.e. by integration to carrier molecules for better therapeutic outcome.

  5. PSMA-Targeted Nano-Conjugates as Dual-Modality (MRI/PET) Imaging Probes for the Noninvasive Detection of Prostate Cancer

    National Research Council Canada - National Science Library

    Sun, Xiankai

    2006-01-01

    ... of prostate cancer diagnosis could be significantly improved. In the first year, we successfully developed standard procedures to reproducibly prepare dextran-coated iron oxide nanoparticles with desired particle size (DLS:7.5 - 35 nm...

  6. Transrectal ultrasound imaging and prostate cancer

    NARCIS (Netherlands)

    Goossen, Tjerk; Wijkstra, Hessel

    2003-01-01

    Prostate cancer is one of the most important causes of death from cancer in men. Ultrasound imaging is frequently used in the diagnosis of prostate cancer. This paper presents an overview of currently available ultrasound imaging techniques. The underlying principles and methods are discussed

  7. Image guided prostate cancer treatments

    Energy Technology Data Exchange (ETDEWEB)

    Bard, Robert L. [Bard Cancer Center, Biofoundation for Angiogenesis Research and Development, New York, NY (United States); Fuetterer, Jurgen J. [Radboud Univ. Nijmegen, Medical Centre (Netherlands). Dept. of Radiology; Sperling, Dan (ed.) [Sperling Prostate Center, Alpha 3TMRI, New York, NY (United States)

    2014-07-01

    Systematic overview of the application of ultrasound and MRI in the diagnosis and treatment of diseases of the lower urinary tract. Detailed information on image-guided therapies, including focused ultrasound, photodynamic therapy, and microwave and laser ablation. Numerous high-quality illustrations based on high-end equipment. Represents the state of the art in Non Invasive Imaging and Minimally Invasive Ablation Treatment (MIAT). Image-Guided Prostate Cancer Treatments is a comprehensive reference and practical guide on the technology and application of ultrasound and MRI in the male pelvis, with special attention to the prostate. The book is organized into three main sections, the first of which is devoted to general aspects of imaging and image-guided treatments. The second section provides a systematic overview of the application of ultrasound and MRI to the diagnosis and treatment of diseases of the lower urinary tract. Performance of the ultrasound and MRI studies is explained, and the normal and abnormal pathological anatomy is reviewed. Correlation with the ultrasound in the same plane is provided to assist in understanding the MRI sequences. Biopsy and interventional procedures, ultrasound-MRI fusion techniques, and image-guided therapies, including focused ultrasound, photodynamic therapy, microwave and laser ablation, are all fully covered. The third section focuses on securing treatment effectiveness and the use of follow-up imaging to ensure therapeutic success and detect tumor recurrence at an early stage, which is vital given that prompt focal treatment of recurrence is very successful. Here, particular attention is paid to the role of Doppler ultrasound and DCE-MRI technologies. This book, containing a wealth of high-quality illustrations based on high-end equipment, will acquaint beginners with the basics of prostate ultrasound and MRI, while more advanced practitioners will learn new skills, means of avoiding pitfalls, and ways of effectively

  8. Clinical targeting recombinant immunotoxins for cancer therapy

    Directory of Open Access Journals (Sweden)

    Li M

    2017-07-01

    Full Text Available Meng Li,1,* Zeng-Shan Liu,1,* Xi-Lin Liu,1,* Qi Hui,2,* Shi-Ying Lu,1 Lin-Lin Qu,1 Yan-Song Li,1 Yu Zhou,1 Hong-Lin Ren,1 Pan Hu1 1Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, China-Japan Union Hospital, The First Hospital, Jilin University, Changchun, 2School of Pharmacy, Wenzhou Medical University, Wenzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Recombinant immunotoxins (RITs are proteins that contain a toxin fused to an antibody or small molecules and are constructed by the genetic engineering technique. RITs can bind to and be internalized by cells and kill cancerous or non-cancerous cells by inhibiting protein synthesis. A wide variety of RITs have been tested against different cancers in cell culture, xenograft models, and human patients during the past several decades. RITs have shown activity in therapy of several kinds of cancers, but different levels of side effects, mainly related to vascular leak syndrome, were also observed in the treated patients. High immunogenicity of RITs limited their long-term or repeat applications in clinical cases. Recent advances in the design of immunotoxins, such as humanization of antibody fragment, PEGylation, and modification of human B- and T-cell epitopes, are overcoming the above mentioned problems, which predict the use of these immunotoxins as a potential therapeutic method to treat cancer patients. Keywords: targeted therapy, hematologic malignancies, solid tumors, vascular leak syndrome, immunogenicity 

  9. Functional differentiation of cytotoxic cancer drugs and targeted cancer therapeutics.

    Science.gov (United States)

    Winkler, Gian C; Barle, Ester Lovsin; Galati, Giuseppe; Kluwe, William M

    2014-10-01

    There is no nationally or internationally binding definition of the term "cytotoxic drug" although this term is used in a variety of regulations for pharmaceutical development and manufacturing of drugs as well as in regulations for protecting medical personnel from occupational exposure in pharmacy, hospital, and other healthcare settings. The term "cytotoxic drug" is frequently used as a synonym for any and all oncology or antineoplastic drugs. Pharmaceutical companies generate and receive requests for assessments of the potential hazards of drugs regularly - including cytotoxicity. This publication is intended to provide functional definitions that help to differentiate between generically-cytotoxic cancer drugs of significant risk to normal human tissues, and targeted cancer therapeutics that pose much lesser risks. Together with specific assessments, it provides comprehensible guidance on how to assess the relevant properties of cancer drugs, and how targeted therapeutics discriminate between cancer and normal cells. The position of several regulatory agencies in the long-term is clearly to regulate all drugs regardless of classification, according to scientific risk based data. Despite ongoing discussions on how to replace the term "cytotoxic drugs" in current regulations, it is expected that its use will continue for the near future. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Research progress in targeted therapy for liver cancer stem cells

    Directory of Open Access Journals (Sweden)

    SHAO Ping

    2015-11-01

    Full Text Available Liver cancer is a malignant tumor. The current operation or chemoradiotherapy cannot achieve a satisfactory effect, and relapse and metastasis are always big problems in the treatment of liver cancer. According to the recent theory of liver cancer stem cells, the genesis, development, relapse, metastasis, and prognosis of liver cancer are all related to liver cancer stem cells. If the liver cancer stem cells are treated by targeted therapy, which would reduce the number of or destroy the stem cells, the relapse, metastasis, and drug resistance after tumor resection may be reduced or eliminated. The progress in targeted therapy for liver cancer stem cells is reviewed here. Although there are many types of targeted therapies for liver cancer stem cells, it is still a key problem that the targeting is not strong enough, which needs to be solved urgently. Whether the dual- or multi-targeting would solve this problem still needs to be confirmed by further experimental studies.

  11. Bioorthogonal Oxime Ligation MediatedIn VivoCancer Targeting.

    Science.gov (United States)

    Tang, Li; Yin, Qian; Xu, Yunxiang; Zhou, Qin; Cai, Kaimin; Yen, Jonathan; Dobrucki, Lawrence W; Cheng, Jianjun

    2015-04-01

    Current cancer targeting relying on specific biological interaction between cell surface antigen and respective antibody or its analogue has proven to be effective in the treatment of different cancers; however, this strategy has its own limitations, such as heterogeneity of cancer cells and immunogenicity of the biomacromolecule binding ligands. Bioorthogonal chemical conjugation has emerged as an attractive alternative to biological interaction for in vivo cancer targeting. Here, we report an in vivo cancer targeting strategy mediated by bioorthogonal oxime ligation. Oxyamine group, the artificial target, is introduced onto 4T1 murine breast cancer cells through liposome delivery and fusion. Poly(ethylene glycol) -polylactide (PEG-PLA) nanoparticle (NP) is surface-functionalized with aldehyde groups as targeting ligands. The improved in vivo cancer targeting of PEG-PLA NPs is achieved through specific and efficient chemical reaction between the oxyamine and aldehyde groups.

  12. Targeting NRF2 signaling for cancer chemoprevention

    International Nuclear Information System (INIS)

    Kwak, Mi-Kyoung; Kensler, Thomas W.

    2010-01-01

    Modulation of the metabolism and disposition of carcinogens through induction of cytoprotective enzymes is one of several promising strategies to prevent cancer. Chemopreventive efficacies of inducers such as dithiolethiones and sulforaphane have been extensively studied in animals as well as in humans. The KEAP1-NRF2 system is a key, but not unilateral, molecular target for these chemopreventive agents. The transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of the expression of a subset of genes, which produce proteins responsible for the detoxication of electrophiles and reactive oxygen species as well as the removal or repair of some of their damage products. It is believed that chemopreventive enzyme inducers affect the interaction between KEAP1 and NRF2 through either mediating conformational changes of the KEAP1 protein or activating phosphorylation cascades targeting the KEAP1-NRF2 complex. These events in turn affect NRF2 stability and trafficking. Recent advances elucidating the underlying structural biology of KEAP1-NRF2 signaling and identification of the gene clusters under the transcriptional control of NRF2 are facilitating understanding of the potential pleiotropic effects of NRF2 activators and discovery of novel classes of potent chemopreventive agents such as the triterpenoids. Although there is appropriately a concern regarding a deleterious role of the KEAP1-NRF2 system in cancer cell biology, especially as the pathway affects cell survival and drug resistance, the development and the use of NRF2 activators as chemopreventive agents still holds a great promise for protection of normal cells from a diversity of environmental stresses that contribute to the burden of cancer and other chronic, degenerative diseases.

  13. Targeting Selectins and Their Ligands in Cancer

    Directory of Open Access Journals (Sweden)

    Alessandro eNatoni

    2016-04-01

    Full Text Available Aberrant glycosylation is a hallmark of cancer cells with increased evidence pointing to a role in tumor progression. In particular, aberrant sialylation of glycoproteins and glycolipids have been linked to increased immune cell evasion, drug evasion, drug resistance, tumor invasiveness, and vascular dissemination leading to metastases. Hypersialylation of cancer cells is largely the result of overexpression of sialyltransferases. Humans differentially express twenty different sialyltransferases in a tissue-specific manner, each of which catalyze the attachment of sialic acids via different glycosidic linkages (2-3; 2-6 or 2-8 to the underlying glycan chain. One important mechanism whereby overexpression of sialyltransferases contributes to an enhanced metastatic phenotype is via the generation of selectin ligands. Selectin ligand function requires the expression of sialyl-Lewis X and its structural-isomer sialyl-Lewis A, which are synthesized by the combined action of alpha 1-3-fucosyltransferases, 2-3-sialyltransferases, 1-4-galactosyltranferases, and N-acetyl--glucosaminyltransferases. The α2-3-sialyltransferases ST3Gal4 and ST3Gal6 are critical to the generation of functional E- and P-selectin ligands and overexpression of these sialyltransferases have been linked to increased risk of metastatic disease in solid tumors and poor outcome in multiple myeloma. Thus, targeting selectins and their ligands as well as the enzymes involved in their generation, in particular sialyltransferases, could be beneficial to many cancer patients. Potential strategies include sialyltransferase inhibition and the use of selectin antagonists, such as glycomimetic drugs and antibodies. Here, we review ongoing efforts to optimize the potency and selectivity of sialyltransferase inhibitors, including the potential for targeted delivery approaches, as well as evaluate the potential utility of selectin inhibitors, which are now in early clinical

  14. A computational imaging target specific detectivity metric

    Science.gov (United States)

    Preece, Bradley L.; Nehmetallah, George

    2017-05-01

    Due to the large quantity of low-cost, high-speed computational processing available today, computational imaging (CI) systems are expected to have a major role for next generation multifunctional cameras. The purpose of this work is to quantify the performance of theses CI systems in a standardized manner. Due to the diversity of CI system designs that are available today or proposed in the near future, significant challenges in modeling and calculating a standardized detection signal-to-noise ratio (SNR) to measure the performance of these systems. In this paper, we developed a path forward for a standardized detectivity metric for CI systems. The detectivity metric is designed to evaluate the performance of a CI system searching for a specific known target or signal of interest, and is defined as the optimal linear matched filter SNR, similar to the Hotelling SNR, calculated in computational space with special considerations for standardization. Therefore, the detectivity metric is designed to be flexible, in order to handle various types of CI systems and specific targets, while keeping the complexity and assumptions of the systems to a minimum.

  15. Alpha-v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy

    National Research Council Canada - National Science Library

    Chen, Xiaoyuan

    2007-01-01

    ...) To demonstrate the feasibility of PET/18F-RGD to image breast tumor growth spread and angiogenesis as well as quantifying alpha v-integrin expression level during breast tumor neovascularization over time. (3...

  16. Alpha-v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy

    National Research Council Canada - National Science Library

    Chen, Xiaoyuan

    2006-01-01

    ...) To demonstrate the feasibility of PET/18F-RGD to image breast tumor growth spread and angiogenesis as well as quantifying alpha-v integrin expression level during breast tumor neovascularization over time. (3...

  17. Targeted polymeric magnetic nanoparticles for brain imaging

    Science.gov (United States)

    Kirthivasan, Bharat; Singh, Dhirender; Raut, Sangram; Bommana, Murali Mohan; Squillante, Emilio, III; Sadoqi, Mostafa

    2012-03-01

    The purpose of this study was to develop targeted polymeric magnetic nanoparticle system for brain imaging. Near infrared dye indocyanine green (ICG) or p-gycoprotein substrate rhodamine 123 (Rh123) were encapsulated along with oleic acid coated magnetic nanoparticles (OAMNP) in a matrix of poly(lactide-co-glycolide) (PLGA) and methoxy poly(ethyleneglycol)-poly(lactide) (Met-PEG-PLA). The nanoparticles were evaluated for morphology, particle size, dye content and magnetite content. The in vivo biodistribution study was carried out using three groups of six male Sprague Dawley rats each. Group I received a saline solution containing the dye, group II received dye-loaded polymeric magnetic nanoparticles without the aid of a magnetic field, and group III received dye-loaded polymeric magnetic nanoparticles with a magnet (8000 G) placed on the head of the rat. After a preset exposure period, the animals were sacrificed and dye concentration was measured in the brain, liver, kidney, lungs and spleen homogenates. Brain sections were fixed, cryotomed and visualized using fluorescence microscopy. The particles were observed to be spherical and had a mean size of 220 nm. The encapsulation efficiency for OAMNP was 57%, while that for ICG was 56% and for Rh123 was 45%. In the biodistribution study, while the majority of the dose for all animals was found in the liver, kidneys and spleen, group III showed a significantly higher brain concentration than the other two groups (p < 0.001). This result was corroborated by the fluorescence microscopy studies, which showed enhanced dye penetration into the brain tissue for group III. Further studies need to be done to elucidate the exact mechanism responsible for the increased brain uptake of dye to help us understand if the magnetic nanoparticles actually penetrate the blood brain barrier or merely deliver a massive load of dye just outside it, thereby triggering passive diffusion into the brain parenchyma. These results reinforce

  18. Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells

    Science.gov (United States)

    Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar

    2014-01-01

    During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. PMID:24872894

  19. Human Neutrophil Peptides 1–3 as Gastric Cancer Tissue Markers Measured by MALDI-Imaging Mass Spectrometry: Implications for Infiltrated Neutrophils as a Tumor Target

    Directory of Open Access Journals (Sweden)

    Chun-Chia Cheng

    2012-01-01

    Full Text Available Objective: Human neutrophil peptides (HNPs -1, -2 and -3 are significantly upregulated and were reported as biomarkers in gastric cancer (GC. However, the tissue location and function of HNPs 1-3 are still unclear in GC, and the spatial distribution of the triad needs to be disclosed. The aims of this study were to investigate the distribution and relationships among HNPs-1, -2 and -3, and assess whether infiltrated neutrophils accumulate in gastric tumor.

  20. Galactosylated manganese ferrite nanoparticles for targeted MR imaging of asialoglycoprotein receptor

    Science.gov (United States)

    Yang, Seung-Hyun; Heo, Dan; Lee, Eugene; Kim, Eunjung; Lim, Eun-Kyung; Lee, Young Han; Haam, Seungjoo; Suh, Jin-Suck; Huh, Yong-Min; Yang, Jaemoon; Park, Sahng Wook

    2013-11-01

    Cancer cells can express specific biomarkers, such as cell membrane proteins and signaling factors. Thus, finding biomarkers and delivering diagnostic agents are important in the diagnosis of cancer. In this study, we investigated a biomarker imaging agent for the diagnosis of hepatic cancers. The asialoglycoprotein receptor (ASGPr) was selected as a biomarker for hepatoma cells and the ASGPr-targetable imaging agent bearing a galactosyl group was prepared using manganese ferrite nanoparticles (MFNP) and galactosylgluconic acid. The utility of the ASGPr-targetable imaging agent, galactosylated MFNP (G-MFNP) was assessed by several methods in ASGPr-expressing HepG2 cells as target cells and ASGPr-deficient MCF7 cells. Physical and chemical properties of G-MFNP were examined using Fourier-transform infrared spectroscopy, dynamic light scattering, zeta potential analysis, and transmission electron microscopy. No significant cytotoxicity was observed in either cell line. Targeting ability was assessed using flow cytometry, magnetic resonance imaging, inductively coupled plasma atomic emission spectroscopy, absorbance analysis, dark-field microscopy, Prussian blue staining, and transmission electron microscopy. We demonstrated that G-MFNP target successfully and bind to ASGPr-expressing HepG2 cells specifically. We suggest that these results will be useful in strategies for cancer diagnoses based on magnetic resonance imaging.

  1. Watching the action unfold: New cryo-EM images capture CRISPR’s interaction with target DNA | Center for Cancer Research

    Science.gov (United States)

    Using the Nobel-prize winning technique of cryo-EM, researchers led by CCR Senior Investigator Sriram Subramaniam, Ph.D., have captured a series of highly detailed images of a protein complex belonging to the CRISPR system that can be used by bacteria to recognize and destroy foreign DNA. The images reveal the molecule’s form before and after its interaction with DNA and help illuminate both how the complex functions and how it can be blocked. Read more... 

  2. Neutron penumbral imaging of laser-fusion targets

    International Nuclear Information System (INIS)

    Lerche, R.A.; Ress, D.B.

    1988-01-01

    Using a new technique, penumbral coded-aperture imaging, the first neutron images of laser-driven, inertial-confinement fusion targets were obtained. With these images the deuterium-tritium burn region within a compressed target can be measured directly. 4 references, 11 figures

  3. MR imaging of prostate cancer

    International Nuclear Information System (INIS)

    Heuck, A.; Scheidler, J.; Sommer, B.; Graser, A.; Mueller-Lisse, U.G.; Massmann, J.

    2003-01-01

    Accurate diagnosis and staging of prostate cancer (PC) is developing into an important health care issue in light of the high incidence of PC and the improvements in stage-adapted therapy. The purpose of this paper is to provide an overview on the current role of MR imaging and MR spectroscopy in the diagnosis and staging of PC.Material and methods Pertinent literature was searched and evaluated to collect information on current clinical indications, study techniques, diagnostic value, and limitations of magnetic resonance imaging and spectroscopy. Major indications for MR imaging of patients with supected PC are to define tumor location before biopsy when clinical or TRUS findings are inconclusive, and to provide accurate staging of histologically proven PC to ascertain effective therapy. Current MR imaging techniques for the evaluation of PC include multiplanar high-resolution T2-weighted FSE and T1-weighted SE sequences using combined endorectal and phased-array coils. Using these techniques, the reported accuracy of MR imaging for the diagnosis of extracapsular tumor extension ranges between 82 and 88% with sensitivities between 80 and 95%, and specificities between 82 and 93%. Typical MR findings of PC in different stages of disease, as well as diagnostic problems, such as chronic prostatitis, biopsy-related hemorrhage and therapy-related changes of prostatic tissue are discussed. In addition, the current perspectives and limitations of MR spectroscopy in PC are summarized. Current MR imaging techniques provide important diagnostic information in the pretherapeutic workup of PC including a high staging accuracy, and is superior to TRUS. (orig.) [de

  4. A Review of Imaging Methods for Prostate Cancer Detection

    Directory of Open Access Journals (Sweden)

    Saradwata Sarkar

    2016-01-01

    Full Text Available Imaging is playing an increasingly important role in the detection of prostate cancer (PCa. This review summarizes the key imaging modalities–multiparametric ultrasound (US, multiparametric magnetic resonance imaging (MRI, MRI-US fusion imaging, and positron emission tomography (PET imaging–-used in the diagnosis and localization of PCa. Emphasis is laid on the biological and functional characteristics of tumors that rationalize the use of a specific imaging technique. Changes to anatomical architecture of tissue can be detected by anatomical grayscale US and T2-weighted MRI. Tumors are known to progress through angiogenesis–-a fact exploited by Doppler and contrast-enhanced US and dynamic contrast-enhanced MRI. The increased cellular density of tumors is targeted by elastography and diffusion-weighted MRI. PET imaging employs several different radionuclides to target the metabolic and cellular activities during tumor growth. Results from studies using these various imaging techniques are discussed and compared.

  5. Targeting Prolyl Peptidases in Triple-Negative Breast Cancer

    Science.gov (United States)

    2017-02-01

    AWARD NUMBER: W81XWH-16-1-0025 TITLE: Targeting Prolyl Peptidases in Triple-Negative Breast Cancer PRINCIPAL INVESTIGATOR: Carl G. Maki, PhD...SUBTITLE Targeting Prolyl Peptidases in Triple-Negative Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0025 5c. PROGRAM ELEMENT NUMBER 6...SUBJECT TERMS Triple negative breast cancer, Prolyl peptidases , Breast cancer treatment, Animal model 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

  6. Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR)

    DEFF Research Database (Denmark)

    Loft, Mathias Dyrberg; Sun, Yao; Liu, Changhao

    2017-01-01

    to the non-spacer version, NODAGA-AE105-NH2. Following radiolabeling with68Ga, we evaluated the in vitro and in vivo performance in mice bearing subcutaneous tumors derived from the uPAR-expressing human GBM cell line U87MG. In vivo PET/CT imaging showed that introduction of PEG spacers more than doubled...

  7. Targeting mitosis for anti-cancer therapy.

    Science.gov (United States)

    Sudakin, Valery; Yen, Timothy J

    2007-01-01

    Basic research that has focused on achieving a mechanistic understanding of mitosis has provided unprecedented molecular and biochemical insights into this highly complex phase of the cell cycle. The discovery process has uncovered an ever-expanding list of novel proteins that orchestrate and coordinate spindle formation and chromosome dynamics during mitosis. That many of these proteins appear to function solely in mitosis makes them ideal targets for the development of mitosis-specific cancer drugs. The clinical successes seen with anti-microtubule drugs such as taxanes and the vinca alkaloids have also encouraged the development of drugs that specifically target mitosis. Drugs that selectively inhibit mitotic kinesins involved in spindle and kinetochore functions, as well as kinases that regulate these activities, are currently in various stages of clinical trials. Our increased understanding of mitosis has also revealed that this process is targeted by inhibitors of farnesyl transferase, histone deacetylase, and Hsp90. Although these drugs were originally designed to block cell proliferation by inhibiting signaling pathways and altering gene expression, it is clear now that these drugs can also directly interfere with the mitotic process. The increased attention to mitosis as a chemotherapeutic target has also raised an important issue regarding the cellular determinants that specify drug sensitivity. One likely contribution is the mitotic checkpoint, a failsafe mechanism that delays mitotic exit so that cells whose chromosomes are not properly attached to the spindle have extra time to correct their errors. As the biochemical activity of the mitotic checkpoint is finite, cells cannot indefinitely sustain the delay, as in cases where cells are treated with anti-mitotic drugs. When the mitotic checkpoint activity is eventually lost, cells will exit mitosis and become aneuploid. While many of the aneuploid cells may die because of massive chromosome imbalance

  8. Target detection method by airborne and spaceborne images fusion based on past images

    Science.gov (United States)

    Chen, Shanjing; Kang, Qing; Wang, Zhenggang; Shen, ZhiQiang; Pu, Huan; Han, Hao; Gu, Zhongzheng

    2017-11-01

    To solve the problem that remote sensing target detection method has low utilization rate of past remote sensing data on target area, and can not recognize camouflage target accurately, a target detection method by airborne and spaceborne images fusion based on past images is proposed in this paper. The target area's past of space remote sensing image is taken as background. The airborne and spaceborne remote sensing data is fused and target feature is extracted by the means of airborne and spaceborne images registration, target change feature extraction, background noise suppression and artificial target feature extraction based on real-time aerial optical remote sensing image. Finally, the support vector machine is used to detect and recognize the target on feature fusion data. The experimental results have established that the proposed method combines the target area change feature of airborne and spaceborne remote sensing images with target detection algorithm, and obtains fine detection and recognition effect on camouflage and non-camouflage targets.

  9. Targeting isocitrate dehydrogenase (IDH) in cancer.

    Science.gov (United States)

    Fujii, Takeo; Khawaja, Muhammad Rizwan; DiNardo, Courtney D; Atkins, Johnique T; Janku, Filip

    2016-05-01

    Isocitrate dehydrogenase (IDH) is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma. The mutated IDH1 and IDH2 proteins have a gain-of-function, neomorphic activity, catalyzing the reduction of α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG) by NADPH. Cancer-associated IDH mutations block normal cellular differentiation and promote tumorigenesis via the abnormal production of the oncometabolite 2-HG. High levels of 2-HG have been shown to inhibit α-KG dependent dioxygenases, including histone and deoxyribonucleic acid (DNA) demethylases, which play a key role in regulating the epigenetic state of cells. Current targeted inhibitors of IDH1 (AG120, IDH305), IDH2 (AG221), and pan-IDH1/2 (AG881) selectively inhibit mutant IDH protein and induce cell differentiation in in vitro and in vivo models. Preliminary results from phase I clinical trials with IDH inhibitors in patients with advanced hematologic malignancies have demonstrated an objective response rate ranging from 31% to 40% with durable responses (>1 year) observed. Furthermore, the IDH inhibitors have demonstrated early signals of activity in solid tumors with IDH mutations, including cholangiocarcinomas and low grade gliomas.

  10. Targeted nanomedicines for the treatment of inflammatory disorders and cancer

    NARCIS (Netherlands)

    Crielaard, B.J.

    2012-01-01

    The therapeutic value of various targeted nanomedicines was evaluated in several inflammatory disorders, including cancer, while exploring which nanocarrier may be most suitable for a specific therapeutic application. First, an overview of drug targeting systems presently available for

  11. Targeting cancer metabolism: dietary and pharmacological interventions

    Science.gov (United States)

    Vernieri, Claudio; Casola, Stefano; Foiani, Marco; Pietrantonio, Filippo; de Braud, Filippo; Longo, Valter

    2016-01-01

    Most tumors display oncogene-driven reprogramming of several metabolic pathways, which are crucial to sustain their growth and proliferation. In recent years, both dietary and pharmacological approaches that target deregulated tumor metabolism are beginning to be considered for clinical applications. Dietary interventions exploit the ability of nutrient-restricted conditions to exert broad biological effects, protecting normal cells, organs and systems, while sensitizing a wide variety of cancer cells to cytotoxic therapies. On the other hand, drugs targeting enzymes or metabolites of crucial metabolic pathways can be highly specific and effective, but must be matched with a responsive tumor, which might rapidly adapt. In this Review, we illustrate how dietary and pharmacological therapies differ in their effect on tumor growth, proliferation and metabolism, and discuss the available preclinical and clinical evidence in favor or against each of them. We also indicate, when appropriate, how to optimize future investigations on metabolic therapies on the basis of tumor- and patient-related characteristics. PMID:27872127

  12. Targeting aggressive cancer stem cells in glioblastoma

    Directory of Open Access Journals (Sweden)

    Tracy Christina Seymour

    2015-07-01

    Full Text Available Glioblastoma (GBM is the most common and fatal type of primary brain tumor. Gliosarcoma (GSM is a rarer and more aggressive variant of GBM that has recently been considered a potentially different disease. Current clinical treatment for both GBM and GSM includes maximal surgical resection followed by post-operative radiotherapy and concomitant and adjuvant chemotherapy. Despite recent advances in treating other solid tumors, treatment for GBM and GSM still remains palliative, with a very poor prognosis and a median survival rate of 12 to 15 months. Treatment failure is a result of a number of causes, including resistance to radiotherapy and chemotherapy. Recent research has applied the cancer stem cells theory of carcinogenesis to these tumors, suggesting the existence of a small subpopulation of glioma stem cells (GSCs within these tumors. GSCs are thought to contribute to tumor progression, treatment resistance and tumor recapitulation post-treatment and have become the focus of novel therapy strategies. Their isolation and investigation suggests that GSCs share critical signalling pathways with normal embryonic and somatic stem cells, but with distinct alterations. Research must focus on identifying these variations as they may present novel therapeutic targets. Targeting pluripotency transcription factors SOX2, OCT4 and NANOG demonstrates promising therapeutic potential that if applied in isolation or together with current treatments may improve overall survival, reduce tumor relapse and achieve a cure for these patients.

  13. Aptamer conjugated paclitaxel and magnetic fluid loaded fluorescently tagged PLGA nanoparticles for targeted cancer therapy

    International Nuclear Information System (INIS)

    Aravind, Athulya; Nair, Remya; Raveendran, Sreejith; Veeranarayanan, Srivani; Nagaoka, Yutaka; Fukuda, Takahiro; Hasumura, Takahashi; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D.

    2013-01-01

    Controlled and targeted drug delivery is an essential criterion in cancer therapy to reduce the side effects caused by non-specific drug release and toxicity. Targeted chemotherapy, sustained drug release and optical imaging have been achieved using a multifunctional nanocarrier constructed from poly (D, L-lactide-co-glycolide) nanoparticles (PLGA NPs), an anticancer drug paclitaxel (PTX), a fluorescent dye Nile red (NR), magnetic fluid (MF) and aptamers (Apt, AS1411, anti-nucleolin aptamer). The magnetic fluid and paclitaxel loaded fluorescently labeled PLGA NPs (MF-PTX-NR-PLGA NPs) were synthesized by a single-emulsion technique/solvent evaporation method using a chemical cross linker bis (sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. Targeting aptamers were then introduced to the particles through the reaction with the cross linker to target the nucleolin receptors over expressed on the cancer cell surface. Specific binding and uptake of the aptamer conjugated magnetic fluid loaded fluorescently tagged PLGA NPs (Apt-MF-NR-PLGA NPs) to the target cancer cells induced by aptamers was observed using confocal microscopy. Cytotoxicity assay conducted in two cell lines (L929 and MCF-7) confirmed that targeted MCF-7 cancer cells were killed while control cells were unharmed. In addition, aptamer mediated delivery resulting in enhanced binding and uptake to the target cancer cells exhibited increased therapeutic effect of the drug. Moreover, these aptamer conjugated magnetic polymer vehicles apart from actively transporting drugs into specifically targeted tumor regions can also be used to induce hyperthermia or for facilitating magnetic guiding of particles to the tumor regions. - Highlights: • Aptamer escorted, theranostic biodegradable PLGA carriers were developed. • Can target cancer cells, control drug release, image and magnetically guide. • Highly specific to the targeted cancer cells thus delivering

  14. Audible sonar images generated with proprioception for target analysis.

    Science.gov (United States)

    Kuc, Roman B

    2017-05-01

    Some blind humans have demonstrated the ability to detect and classify objects with echolocation using palatal clicks. An audible-sonar robot mimics human click emissions, binaural hearing, and head movements to extract interaural time and level differences from target echoes. Targets of various complexity are examined by transverse displacements of the sonar and by target pose rotations that model movements performed by the blind. Controlled sonar movements executed by the robot provide data that model proprioception information available to blind humans for examining targets from various aspects. The audible sonar uses this sonar location and orientation information to form two-dimensional target images that are similar to medical diagnostic ultrasound tomograms. Simple targets, such as single round and square posts, produce distinguishable and recognizable images. More complex targets configured with several simple objects generate diffraction effects and multiple reflections that produce image artifacts. The presentation illustrates the capabilities and limitations of target classification from audible sonar images.

  15. Cancer chemoprevention by targeting the epigenome.

    Science.gov (United States)

    Huang, Joseph; Plass, Christoph; Gerhauser, Clarissa

    2011-12-01

    The term "epigenetics" refers to modifications in gene expression caused by heritable, but potentially reversible, changes in DNA methylation and chromatin structure. Given the fact that epigenetic modifications occur early in carcinogenesis and represent potentially initiating events in cancer development, they have been identified as promising new targets for prevention strategies. The present review will give a comprehensive overview of the current literature on chemopreventive agents and their influence on major epigenetic mechanisms, that is DNA methylation, histone acetylation and methylation, and microRNAs, both in vitro and in rodent and human studies, taking into consideration specific mechanisms of action, target sites, concentrations, methods used for analysis, and outcome. Chemopreventive agents with reported mechanisms targeting the epigenome include micronutrients (folate, selenium, retinoic acid, Vit. E), butyrate, polyphenols (from green tea, apples, coffee, and other dietary sources), genistein and soy isoflavones, parthenolide, curcumin, ellagitannin, indol-3-carbinol (I3C) and diindolylmethane (DIM), mahanine, nordihydroguaiaretic acid (NDGA), lycopene, sulfur-containing compounds from Allium and cruciferous vegetables (sulforaphane, phenylethyl isothiocyanate (PEITC), phenylhexyl isothiocyanate (PHI), diallyldisulfide (DADS), allyl mercaptan (AM)), antibiotics (mithramycin A, apicidin), pharmacological agents (celecoxib, DFMO, 5-aza-2'-deoxycytidine and zebularine), compounds affecting sirtuin activity (resveratrol, dihydrocoumarin, cambinol), inhibitors of histone acetyl transferases (anacardic acid, garcinol, ursodeoxycholic acid), and relatively unexplored modulators of histone lysine methylation (chaetocin, polyamine analogues, n-3 polyunsaturated fatty acids). Their effects on global DNA methylation, tumor suppressor genes silenced by promoter methylation, histone modifications, and miRNAs deregulated during carcinogenesis have potential

  16. New targets for immunotherapy-based treatment of HPV-related cancers | Center for Cancer Research

    Science.gov (United States)

    Scientists at the Center for Cancer Research and three other cancer research institutions show that immunotherapy treatments that resulted in complete regression of metastatic cervical cancer largely targeted two non-viral antigens. Read more…  

  17. Real time laser speckle imaging monitoring vascular targeted photodynamic therapy

    Science.gov (United States)

    Goldschmidt, Ruth; Vyacheslav, Kalchenko; Scherz, Avigdor

    2017-02-01

    Laser speckle imaging is a technique that has been developed to non-invasively monitor in vivo blood flow dynamics and vascular structure, at high spatial and temporal resolution. It can record the full-field spatio-temporal characteristics of microcirculation and has therefore, often been used to study the blood flow in tumors after photodynamic therapy (PDT). Yet, there is a paucity of reports on real-time laser speckle imaging (RTLSI) during PDT. Vascular-targeted photodynamic therapy (VTP) with WST11, a water-soluble bacteriochlorophyll derivative, achieves tumor ablation through rapid occlusion of the tumor vasculature followed by a cascade of events that actively kill the tumor cells. WST11-VTP has been already approved for treatment of early/intermediate prostate cancer at a certain drug dose, time and intensity of illumination. Application to other cancers may require different light dosage. However, incomplete vascular occlusion at lower light dose may result in cancer cell survival and tumor relapse while excessive light dose may lead to toxicity of nearby healthy tissues. Here we provide evidence for the feasibility of concomitant RTLSI of the blood flow dynamics in the tumor and surrounding normal tissues during and after WST11-VTP. Fast decrease in the blood flow is followed by partial mild reperfusion and a complete flow arrest within the tumor by the end of illumination. While the primary occlusion of the tumor feeding arteries and draining veins agrees with previous data published by our group, the late effects underscore the significance of light dose control to minimize normal tissue impairment. In conclusion- RTSLI application should allow to optimize VTP efficacy vs toxicity in both the preclinical and clinical arenas.

  18. Nanotargeted Radionuclides for Cancer Nuclear Imaging and Internal Radiotherapy

    Directory of Open Access Journals (Sweden)

    Gann Ting

    2010-01-01

    Full Text Available Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers being able to deliver radionuclide payloads in a site or molecular selective manner to improve the efficacy and safety of cancer imaging and therapy. Radionuclides of auger electron-, α-, β-, and γ-radiation emitters have been surface-bioconjugated or after-loaded in nanoparticles to improve the efficacy and reduce the toxicity of cancer imaging and therapy in preclinical and clinical studies. This article provides a brief overview of current status of applications, advantages, problems, up-to-date research and development, and future prospects of nanotargeted radionuclides in cancer nuclear imaging and radiotherapy. Passive and active nanotargeting delivery of radionuclides with illustrating examples for tumor imaging and therapy are reviewed and summarized. Research on combing different modes of selective delivery of radionuclides through nanocarriers targeted delivery for tumor imaging and therapy offers the new possibility of large increases in cancer diagnostic efficacy and therapeutic index. However, further efforts and challenges in preclinical and clinical efficacy and toxicity studies are required to translate those advanced technologies to the clinical applications for cancer patients.

  19. Nanotargeted Radionuclides for Cancer Nuclear Imaging and Internal Radiotherapy

    Science.gov (United States)

    Ting, Gann; Chang, Chih-Hsien; Wang, Hsin-Ell; Lee, Te-Wei

    2010-01-01

    Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers being able to deliver radionuclide payloads in a site or molecular selective manner to improve the efficacy and safety of cancer imaging and therapy. Radionuclides of auger electron-, α-, β-, and γ-radiation emitters have been surface-bioconjugated or after-loaded in nanoparticles to improve the efficacy and reduce the toxicity of cancer imaging and therapy in preclinical and clinical studies. This article provides a brief overview of current status of applications, advantages, problems, up-to-date research and development, and future prospects of nanotargeted radionuclides in cancer nuclear imaging and radiotherapy. Passive and active nanotargeting delivery of radionuclides with illustrating examples for tumor imaging and therapy are reviewed and summarized. Research on combing different modes of selective delivery of radionuclides through nanocarriers targeted delivery for tumor imaging and therapy offers the new possibility of large increases in cancer diagnostic efficacy and therapeutic index. However, further efforts and challenges in preclinical and clinical efficacy and toxicity studies are required to translate those advanced technologies to the clinical applications for cancer patients. PMID:20811605

  20. Molecular Imaging of Breast Cancer: Present and future directions

    Directory of Open Access Journals (Sweden)

    David eAlcantara

    2014-12-01

    Full Text Available Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumour is located in the body, but also to visualize the expression and activity of specific molecules (e.g. proteases and protein kinases and biological processes (e.g. apoptosis, angiogenesis, and metastasis that influence tumour behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

  1. Targeting apoptosis pathways in lung cancer

    NARCIS (Netherlands)

    Pore, Milind M.; Hiltermann, T. Jeroen N.; Kruyt, Frank A. E.

    2013-01-01

    Lung cancer is a devastating disease with a poor prognosis. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) represent different forms of lung cancer that are associated with distinct genetic causes and display different responses to therapy in the clinic. Whereas SCLC is often

  2. A MSLN-targeted multifunctional nanoimmunoliposome for MRI and targeting therapy in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Deng L

    2012-09-01

    Full Text Available Li Deng,1,# Xingfa Ke,4,# Zhiying He,3,# Daoqiu Yang,5 Hai Gong,6 Yingying Zhang,1 Xiaolong Jing,4 Jianzhong Yao,2 Jianming Chen11Department of Pharmaceutics, 2Department of Medicinal Chemistry, School of Pharmacy, 3Department of Cell Biology, Second Military Medical University, Shanghai, People's Republic of China; 4Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian, People's Republic of China; 5Department of Dermatology, 107th Hospital of PLA, Yantai, People's Republic of China; 6Department of Radiation Oncology, General Hospital of Jinan Military Region, Jinan, People’s Republic of China#These authors contributed equally to this workAbstract: Pancreatic cancer is a highly lethal disease with a 5-year survival rate less than 5% due to the lack of an early diagnosis method and effective therapy. To provide a novel early diagnostic method and targeted therapy for pancreatic cancer, a multifunctional nanoimmunoliposome with high loading of ultrasmall superparamagnetic iron oxides (USPIOs and doxorubicin (DOX was prepared by transient binding and reverse-phase evaporation method, and was conjugated with anti-mesothelin monoclonal antibody by post-insertion method to target anti-mesothelin-overexpressed pancreatic cancer cells. The in vitro and in vivo properties of this anti-mesothelin antibody-conjugated PEGlyated liposomal DOX and USPIOs (M-PLDU; and PEGlyated nanoimmunoliposome without antibody conjugation [PLDU] were evaluated both in human pancreatic cancer cell line Panc-1 cell and in a pancreatic cancer xenograft animal model. Results showed that M-PLDUs were spherical and uniform with a diameter about ~180 nm, with a zeta potential of about −28~−30 mV, and had good efficacy encapsulating DOX and USPIOs. The in vitro study demonstrated that M-PLDUs possessed good magnetic resonance imaging (MRI capability with a transverse relaxivity (r2 of about 58.5 mM–1 • s–1. Confocal microscopy showed more

  3. Benchmarks for targeted alpha therapy for cancer

    International Nuclear Information System (INIS)

    Allen, J.B.

    2011-01-01

    Full text: Targeted alpha therapy (TAT) needs to achieve certain benchmarks if t is to find its way into the clinic. This paper reviews the status of benchmarks for dose normalisation, microdosimetry, response of micrometastases to therapy, maximum tolerance doses and adequate supplies of alpha emitting radioisotopes. In comparing dose effect for different alpha immunoconjugates (IC), patients and diseases, it is appropriate to normalise dose according to specific factors that affect the efficacy of the treatment. Body weight and body surface area are two commonly used criteria. However, more advanced criteria are required, such as the volume of distribution. Alpha dosimetry presents a special challenge in clinical trials. Monte Carlo calculations can be used to determine specific energies, but these need validation. This problem could be resolved with micronuclei biological dosimetry and mutagenesis studies of radiation Jam age. While macroscopic disease can be monitored, the impact of therapy on subclinical microscopic disease is a real problem. Magnetic cell separation of cancer cells in the blood with magnetic microspheres coated with the targeting monoclonal antibody could provide the response data. Alpha therapy needs first to establish maximum tolerance doses for practical acceptance. This has been determined with 213Bi-IC for acute myelogenous leukaemia at ∼ I mCi/kg. The maximum tolerance dose has not yet been established for metastatic melanoma, but the efficacious dose for some melanomas is less than 0.3 mCi/kg and for intra-cavity therapy of GBM it is ∼ 0.14 mCi/kg for 211 At-Ie. In the case of Ra-223 for bone cancer, the emission of four alphas with a total energy of 27 MeV results in very high cytotoxicity and an effective dose of only ∼ 5 μCi/kg. The limited supplies of Ac-225 available after separation from Th-229 are adequate for clinical trials. However, should TAT become a clinical procedure, then new supplies must be found. Accelerator

  4. Urinary bladder cancer: role of MR imaging.

    Science.gov (United States)

    Verma, Sadhna; Rajesh, Arumugam; Prasad, Srinivasa R; Gaitonde, Krishnanath; Lall, Chandana G; Mouraviev, Vladimir; Aeron, Gunjan; Bracken, Robert B; Sandrasegaran, Kumaresan

    2012-01-01

    Urinary bladder cancer is a heterogeneous disease with a variety of pathologic features, cytogenetic characteristics, and natural histories. It is the fourth most common cancer in males and the tenth most common cancer in females. Urinary bladder cancer has a high recurrence rate, necessitating long-term surveillance after initial therapy. Early detection is important, since up to 47% of bladder cancer-related deaths may have been avoided. Conventional computed tomography (CT) and magnetic resonance (MR) imaging are only moderately accurate in the diagnosis and local staging of bladder cancer, with cystoscopy and pathologic staging remaining the standards of reference. However, the role of newer MR imaging sequences (eg, diffusion-weighted imaging) in the diagnosis and local staging of bladder cancer is still evolving. Substantial advances in MR imaging technology have made multiparametric MR imaging a feasible and reasonably accurate technique for the local staging of bladder cancer to optimize treatment. In addition, whole-body CT is the primary imaging technique for the detection of metastases in bladder cancer patients, especially those with disease that invades muscle. © RSNA, 2012.

  5. Images of gastric cancer stages

    International Nuclear Information System (INIS)

    Castro Aragon, I.M.

    1999-01-01

    The present work has the objective to review the importance of the images in the preoperating stage of the gastric cancer. It has been emphasized in the modalities of transabdominal ultrasound as much as endoscopic and TAC since they are most valuable in the stage. Certainly the importance of conventional radiology (gastroduodenal series) is also valuable in the stage of the tumor, specially in considering the depth of the same one. In order to make this overhaul, the recent bibliography was consulted but, specially the published one by Japaneses since they follow a classification and methodology different from the used one in most of the countries that belong to the World-wide Organization of the Health. They made an overhaul of approximately 200 cases of patients who have been diagnosed and treated in the Center of Detection of Gastric Cancer of Cartago. In each case review the file, radiological, sonographic and pathological studies, and the cases were chosen that better illustrated the exposed subjects. (Author) [es

  6. Integrin α3β1 as a breast cancer target.

    Science.gov (United States)

    Subbaram, Sita; Dipersio, C Michael

    2011-10-01

    Integrin receptors for cell adhesion to the extracellular matrix have important roles in all stages of cancer progression and metastasis. Since the integrin family was discovered in the early 1980's, many studies have identified critical adhesion and signaling functions for integrins expressed on tumor cells, endothelial cells and other cell types of the tumor microenvironment, in controlling proliferation, survival, migration and angiogenesis. In recent years, the laminin-binding integrin α3β1 has emerged as a potentially promising anti-cancer target on breast cancer cells. Studies from the past decade that implicate integrins as promising anti-cancer targets and the development of integrin antagonists as anti-cancer therapeutics. Recent preclinical studies that have identified the laminin-binding integrin α3β1 as an appealing anti-cancer target and the knowledge gaps that must be closed to fully exploit this integrin as a therapeutic target for breast cancer. Although the tumor-promoting functions of α3β1 implicate this integrin as a promising therapeutic target on breast cancer cells, successful exploitation of this integrin as an anti-cancer target will require a better understanding of the molecular mechanisms whereby it regulates specific tumor cell behaviors and the identification of the most appropriate α3β1 functions to antagonize on breast cancer cells.

  7. 90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: response to treatment at targeted doses of 135-150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging.

    Science.gov (United States)

    Lewandowski, Robert J; Thurston, Kenneth G; Goin, James E; Wong, Ching-Yee O; Gates, Vanessa L; Van Buskirk, Mark; Geschwind, Jean-Francois H; Salem, Riad

    2005-12-01

    The purpose of this phase II study was to determine the safety and efficacy of TheraSphere treatment (90Y microspheres) in patients with liver-dominant colorectal metastases in whom standard therapies had failed or were judged to be inappropriate. Twenty-seven patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 135-150 Gy. Safety and toxicity were assessed according to the National Cancer Institute's Common Toxicity Criteria, version 3.0. Response was assessed with use of computed tomography (CT) and was correlated with response on [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Survival from first treatment was estimated with use of the Kaplan-Meier method. Tumor response measured by FDG PET imaging exceeded that measured by CT imaging for the first (88% vs 35%) and second (73% vs 36%) treated lobes. Tumor replacement of 25% or less (vs >25%) was associated with a statistically significant increase in median survival (339 days vs 162 days; P = .002). Treatment-related toxicities included mild fatigue (n = 13; 48%), nausea (n = 4; 15%), and vague abdominal pain (n = 5; 19%). There was one case of radiation-induced gastritis from inadvertent deposition of microspheres to the gastrointestinal tract (n = 1; 4%). Three patients (11%) experienced ascites/pleural effusion after treatment with TheraSphere as a consequence of liver failure in advanced-stage metastatic disease. With the exception of these three patients whose sequelae were not considered to be related to treatment, all observed toxicities were transient and resolved without medical intervention. TheraSphere administration appears to provide stabilization of liver disease with minimal toxicity in patients in whom standard systemic chemotherapy regimens have failed.

  8. Predicting selective drug targets in cancer through metabolic networks

    Science.gov (United States)

    Folger, Ori; Jerby, Livnat; Frezza, Christian; Gottlieb, Eyal; Ruppin, Eytan; Shlomi, Tomer

    2011-01-01

    The interest in studying metabolic alterations in cancer and their potential role as novel targets for therapy has been rejuvenated in recent years. Here, we report the development of the first genome-scale network model of cancer metabolism, validated by correctly identifying genes essential for cellular proliferation in cancer cell lines. The model predicts 52 cytostatic drug targets, of which 40% are targeted by known, approved or experimental anticancer drugs, and the rest are new. It further predicts combinations of synthetic lethal drug targets, whose synergy is validated using available drug efficacy and gene expression measurements across the NCI-60 cancer cell line collection. Finally, potential selective treatments for specific cancers that depend on cancer type-specific downregulation of gene expression and somatic mutations are compiled. PMID:21694718

  9. Revealing targeted therapy for human cancer by gene module maps

    NARCIS (Netherlands)

    Wong, David J.; Nuyten, Dimitry S. A.; Regev, Aviv; Lin, Meihong; Adler, Adam S.; Segal, Eran; van de Vijver, Marc J.; Chang, Howard Y.

    2008-01-01

    A major goal of cancer research is to match specific therapies to molecular targets in cancer. Genome-scale expression profiling has identified new subtypes of cancer based on consistent patterns of variation in gene expression, leading to improved prognostic predictions. However, how these new

  10. Molecular pathways and therapeutic targets in lung cancer

    Science.gov (United States)

    Shtivelman, Emma; Hensing, Thomas; Simon, George R.; Dennis, Phillip A.; Otterson, Gregory A.; Bueno, Raphael; Salgia, Ravi

    2014-01-01

    Lung cancer is still the leading cause of cancer death worldwide. Both histologically and molecularly lung cancer is heterogeneous. This review summarizes the current knowledge of the pathways involved in the various types of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. It describes the major pathways and molecular alterations implicated in the development and progression of non-small cell lung cancer (adenocarcinoma and squamous cancer), and of small cell carcinoma, emphasizing the molecular alterations comprising the specific blueprints in each group. The approved and investigational targeted therapies as well as the immune therapies, and clinical trials exploring the variety of targeted approaches to treatment of lung cancer are the main focus of this review. PMID:24722523

  11. Targeting Gallium to Cancer Cells through the Folate Receptor

    Directory of Open Access Journals (Sweden)

    Nerissa Viola-Villegas

    2008-01-01

    Full Text Available The development of gallium(III compounds as anti-cancer agents for both treatment and diagnosis is a rapidly developing field of research. Problems remain in exploring the full potential of gallium(III as a safe and successful therapeutic agent or as an imaging agent. One of the major issues is that gallium(III compounds have little tropism for cancer cells. We have combined the targeting properties of folic acid (FA with long chain liquid polymer poly(ethylene glycol (PEG ‘spacers’. This FA-PEG unit has been coupled to the gallium coordination complex of 1,4,7,10-tetraazacyclo-dodecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA through amide linkages for delivery into target cells overexpressing the folate receptor (FR. In vitro cytotoxicity assays were conducted against a multi-drug resistant ovarian cell line (A2780/AD that overexpresses the FR and contrasted against a FR free Chinese hamster ovary (CHO cell line. Results are rationalized taking into account stability studies conducted in RPMI 1640 media and HEPES buffer at pH 7.4.

  12. Targeting Gallium to Cancer Cells through the Folate Receptor

    Directory of Open Access Journals (Sweden)

    Nerissa Viola-Villegas

    2008-01-01

    Full Text Available The development of gallium(III compounds as anti-cancer agents for both treatment and diagnosis is a rapidly developing field of research. Problems remain in exploring the full potential of gallium(III as a safe and successful therapeutic agent or as an imaging agent. One of the major issues is that gallium(III compounds have little tropism for cancer cells. We have combined the targeting properties of folic acid (FA with long chain liquid polymer poly(ethylene glycol (PEG 'spacers’. This FA-PEG unit has been coupled to the gallium coordination complex of 1,4,7,10-tetraazacyclo-dodecane-N, N′, N′, N′′-tetraacetic acid (DOTA through amide linkages for delivery into target cells overexpressing the folate receptor (FR. In vitro cytotoxicity assays were conducted against a multi-drug resistant ovarian cell line (A2780/AD that overexpresses the FR and contrasted against a FR free Chinese hamster ovary (CHO cell line. Results are rationalized taking into account stability studies conducted in RPMI 1640 media and HEPES buffer at pH 7.4.

  13. Radiolabeled Cetuximab Conjugates for EGFR Targeted Cancer Diagnostics and Therapy

    Directory of Open Access Journals (Sweden)

    Wiebke Sihver

    2014-03-01

    Full Text Available The epidermal growth factor receptor (EGFR has evolved over years into a main molecular target for the treatment of different cancer entities. In this regard, the anti-EGFR antibody cetuximab has been approved alone or in combination with: (a chemotherapy for treatment of colorectal and head and neck squamous cell carcinoma and (b with external radiotherapy for treatment of head and neck squamous cell carcinoma. The conjugation of radionuclides to cetuximab in combination with the specific targeting properties of this antibody might increase its therapeutic efficiency. This review article gives an overview of the preclinical studies that have been performed with radiolabeled cetuximab for imaging and/or treatment of different tumor models. A particularly promising approach seems to be the treatment with therapeutic radionuclide-labeled cetuximab in combination with external radiotherapy. Present data support an important impact of the tumor micromilieu on treatment response that needs to be further validated in patients. Another important challenge is the reduction of nonspecific uptake of the radioactive substance in metabolic organs like liver and radiosensitive organs like bone marrow and kidneys. Overall, the integration of diagnosis, treatment and monitoring as a theranostic approach appears to be a promising strategy for improvement of individualized cancer treatment.

  14. Targeting Epigenetics Therapy for Estrogen Receptor-Negative Breast Cancers

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-13-1-0400 TITLE: Targeting Epigenetics Therapy for Estrogen Receptor-Negative Breast Cancers PRINCIPAL INVESTIGATOR...Targeting Epigenetics Therapy for Estrogen Receptor-Negative Breast Cancers 5b. GRANT NUMBER W81XWH-13-1-0400 5c. PROGRAM ELEMENT NUMBER 6...negative breast cancer, epigenetics , nuclear hormone receptor, estrogen Overall Project Summary Flavin-dependent, lysine-specific protein

  15. Targeting histone abnormality in triple negative breast cancer

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-14-1-0238 TITLE: Targeting histone abnormality in triple negative breast cancer PRINCIPAL INVESTIGATOR: Steffi...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting histone abnormality in triple negative breast cancer 5b. GRANT NUMBER W81XWH-14-1-0238 5c...PDXs). In addition, two teams collaborated in studying the functional role of LSD2 in breast cancer progression. The interactive studies between two

  16. Theranostic Potential of Targeted Nanoparticles for Brain Cancer.

    Science.gov (United States)

    Bhatt, Ajita; Gurnany, Ekta; Modi, Anuj; Gulbake, Arvind; Jain, Aviral

    2017-01-01

    Cancer is one of the most important causes of morbidity and mortality all across the world. On an average, every year approximately 238,000 new cases of brain and other central nervous system tumors are diagnosed around the world. Amongst all, tumors of brain account for nearly 85% to 90% of all primary central nervous system (CNS) tumors. Regardless of tremendous scientific efforts to develop newer diagnostic techniques and latest therapy, the management of brain cancer is still a challenge in neuro-oncology. Inadequate concentration of chemotherapeutics at the site of tumor restricts the complete destruction of malignant cells due to the presence of blood brain barrier. Besides, there is a necessity for improvement in tumor imaging for better characterization and visualization of tumor cells for surgical procedure. Nanoparticles offer the advantages upon many of these concerns i.e., diagnosis, capability to target therapeutic agents to the tumor sites and the ability of getting across the blood-brain barrier. Thus utilization of nanoparticles may lead to breakthrough in brain cancer management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Observer variation in target volume delineation of lung cancer related to radiation oncologist-computer interaction: a 'Big Brother' evaluation.

    NARCIS (Netherlands)

    Steenbakkers, R.J.; Duppen, J.C.; Fitton, I.; Deurloo, K.E.; Zijp, L.; Uitterhoeve, A.L.; Rodrigus, P.T.; Kramer, G.W.P.M.; Bussink, J.; Jaeger, K. de; Belderbos, J.S.; Hart, A.A.M.; Nowak, P.J.; Herk, M. van; Rasch, C.R.

    2005-01-01

    BACKGROUND AND PURPOSE: To evaluate the process of target volume delineation in lung cancer for optimization of imaging, delineation protocol and delineation software. PATIENTS AND METHODS: Eleven radiation oncologists (observers) from five different institutions delineated the Gross Tumor Volume

  18. Potential nanotechnologies and molecular targets in the quest for efficient chemotherapy in ovarian cancer.

    Science.gov (United States)

    Rhoda, Khadija; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Pillay, Viness

    2015-04-01

    Ovarian cancer, considered one of the most fatal gynecological cancers, goes largely undiagnosed until metastasis presents itself, usually once the patient is in the final stages and thus, too late for worthwhile therapy. Targeting this elusive disease in its early stages would improve the outcome for most patients, while the information generated thereof would increase the possibility of preventative mechanisms of therapy. This review discusses various molecular targets as possible moieties to be incorporated in a holistic drug delivery system or the more aptly termed 'theranostic' system. These molecular targets can be used for targeting, visualizing, diagnosing, and ultimately, treating ovarian cancer in its entirety. Currently implemented nanoframeworks, such as nanomicelles and nanoliposomes, are described and the effectiveness of nanostructures in tumor targeting, treatment functions, and overcoming the drug resistance challenge is discussed. Novel nanotechnology strategies such as the development of nanoframeworks decorated with targeted ligands of a molecular nature may provide an efficient chemotherapy, especially when instituted in combination with imaging, diagnostic, and ultimately, therapeutic moieties. An imperative aspect of utilizing nanotechnology in the treatment of ovarian cancer is the flexibility of the drug delivery system and its ability to overcome standard obstacles such as: i) successfully treating the desired cells through direct targeting; ii) reducing toxicity levels of treatment by achieving direct targeting; and iii) delivery of targeted therapy using an efficient vehicle that is exceptionally degradable in response to a particular stimulus. The targeting of ovarian cancer in its early stages using imaging and diagnostic nanotechnology is an area that can be improved upon by combining therapeutic moieties with molecular biomarkers. The nanotechnology and molecular markers mentioned in this review have generally been used for either

  19. Targeting the Ron-DEK Signaling Axis in Breast Cancer

    Science.gov (United States)

    2014-09-01

    2014.173 INTRODUCTION Despite high survival rates for early-stage breast cancer , it is still the second leading cause of cancer - related deaths in the...164: 285–293. 37 Adams AK, Hallenbeck GE, Casper KA, Patil YJ, Wilson KM, Kimple RJ et al. DEK promotes HPV -positive and -negative head and neck cancer ...AWARD NUMBER: W81XWH-12-1-0194 TITLE: Targeting the Ron-DEK Signaling Axis in Breast Cancer PRINCIPAL INVESTIGATORS: Dr

  20. Multiparametric magnetic resonance imaging of prostate cancer

    Directory of Open Access Journals (Sweden)

    Sandeep S Hedgire

    2012-01-01

    Full Text Available In India, prostate cancer has an incidence rate of 3.9 per 100,000 men and is responsible for 9% of cancer-related mortality. It is the only malignancy that is diagnosed with an apparently blind technique, i.e., transrectal sextant biopsy. With increasing numbers of high-Tesla magnetic resonance imaging (MRI equipment being installed in India, the radiologist needs to be cognizant about endorectal MRI and multiparametric imaging for prostate cancer. In this review article, we aim to highlight the utility of multiparamteric MRI in prostate cancer. It plays a crucial role, mainly in initial staging, restaging, and post-treatment follow-up.

  1. Image thresholding in the high resolution target movement monitor

    Science.gov (United States)

    Moss, Randy H.; Watkins, Steve E.; Jones, Tristan H.; Apel, Derek B.; Bairineni, Deepti

    2009-03-01

    Image thresholding in the High Resolution Target Movement Monitor (HRTMM) is examined. The HRTMM was developed at the Missouri University of Science and Technology to detect and measure wall movements in underground mines to help reduce fatality and injury rates. The system detects the movement of a target with sub-millimeter accuracy based on the images of one or more laser dots projected on the target and viewed by a high-resolution camera. The relative position of the centroid of the laser dot (determined by software using thresholding concepts) in the images is the key factor in detecting the target movement. Prior versions of the HRTMM set the image threshold based on a manual, visual examination of the images. This work systematically examines the effect of varying threshold on the calculated centroid position and describes an algorithm for determining a threshold setting. First, the thresholding effects on the centroid position are determined for a stationary target. Plots of the centroid positions as a function of varying thresholds are obtained to identify clusters of thresholds for which the centroid position does not change for stationary targets. Second, the target is moved away from the camera in sub-millimeter increments and several images are obtained at each position and analyzed as a function of centroid position, target movement and varying threshold values. With this approach, the HRTMM can accommodate images in batch mode without the need for manual intervention. The capability for the HRTMM to provide automated, continuous monitoring of wall movement is enhanced.

  2. A comparison of prostate tumor targeting strategies using magnetic resonance imaging-targeted, transrectal ultrasound-guided fusion biopsy.

    Science.gov (United States)

    Martin, Peter R; Cool, Derek W; Fenster, Aaron; Ward, Aaron D

    2018-03-01

    Magnetic resonance imaging (MRI)-targeted, three-dimensional (3D) transrectal ultrasound (TRUS)-guided prostate biopsy aims to reduce the 21-47% false-negative rate of clinical two-dimensional (2D) TRUS-guided systematic biopsy, but continues to yield false-negative results. This may be improved via needle target optimization, accounting for guidance system errors and image registration errors. As an initial step toward the goal of optimized prostate biopsy targeting, we investigated how needle delivery error impacts tumor sampling probability for two targeting strategies. We obtained MRI and 3D TRUS images from 49 patients. A radiologist and radiology resident assessed these MR images and contoured 81 suspicious regions, yielding tumor surfaces that were registered to 3D TRUS. The biopsy system's root-mean-squared needle delivery error (RMSE) and systematic error were modeled using an isotropic 3D Gaussian distribution. We investigated two different prostate tumor-targeting strategies using (a) the tumor's centroid and (b) a ring in the lateral-elevational plane. For each simulation, targets were spaced at equal arc lengths on a ring with radius equal to the systematic error magnitude. A total of 1000 biopsy simulations were conducted for each tumor, with RMSE and systematic error magnitudes ranging from 1 to 6 mm. The difference in median tumor sampling probability and probability of obtaining a 50% core involvement was determined for ring vs centroid targeting. Our simulation results indicate that ring targeting outperformed centroid targeting in situations where systematic error exceeds RMSE. In these instances, we observed statistically significant differences showing 1-32% improvement in sampling probability due to ring targeting. Likewise, we observed statistically significant differences showing 1-39% improvement in 50% core involvement probability due to ring targeting. Our results suggest that the optimal targeting scheme for prostate biopsy depends on

  3. Advances in imaging diagnosis of liver cancer

    Directory of Open Access Journals (Sweden)

    ZHANG Chunyu

    2017-07-01

    Full Text Available Liver biopsy is the gold standard for the diagnosis of primary liver cancer, but it is an invasive examination. At present, imaging has become the preferred method for the diagnosis of liver cancer. This article summarizes new imaging methods and techniques for the diagnosis and evaluation of primary liver cancer, including contrast-enhanced ultrasound, CT perfusion imaging, diffusion-weighted imaging-intravoxel incoherent motion, IDEAL IQ sequence, dynamic contrast-enhanced MRI, and hepatocyte-specific contrast-enhanced imaging, and points out that diagnostic imaging can not only evaluate the degree of tumor differentiation, blood supply and perfusion, and invasiveness of lesions, but also predict the prognosis and evaluate liver function. Therefore, it can provide a reference for clinical diagnosis and treatment.

  4. Two novel approaches targeting cancer cell membrane for tumor therapy.

    Science.gov (United States)

    Feng, Yingzhu; Wang, Bochu; Cao, Yang; He, Rui

    2013-04-01

    Disruption of normal cell function by chemicals, UV radiation or viruses can cause various cancer. Drugs that have been developed for cancer therapy bind to various targets to correct disorder cell behavior, repair damaged DNA or promote cell apoptosis. However, there is rare study that focuses on cancer cell membrane as target. We propose two approaches for achieving our goal. One is to use phospholipase A2 (PLA2) to cleave phospholipid heads of the bilayer of cancer cells. Because PLA2 has unique Ca(2+) catalytic site and the pH of healthy tissue cells should be slightly alkaline at 7.2-7.5, it can be easily protected by CO3(2-) in the form of PLA2-CaCO3. While PLA2-CaCO3 accumulate in cancer cells in the acidic microenvironment of which the pH is below 7, it could be converted to active state (PLA2-Ca(2+)) which can intensively damage the cancer cell membrane. The other one is to use both monoclonal antibodies and dimethylsulfoxide (DMSO). The internalization of targeted cancer cell antibodies could change the curvature of cell membrane from order state to disorder state, therefore strong detergent DMSO can destroy cancer cells at extreme low concentration. These two approaches present no harm for normal cells, therefore, drugs targeted cancer cell membrane might become a new and high effective clinical cancer therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. London forum targets Africa's cancer crisis

    International Nuclear Information System (INIS)

    2007-01-01

    Full text: Africa stands on the brink of a cancer epidemic, with more than a million new cases a year by 2020. Raising awareness of the threat is one of the biggest challenges facing the global health community today. Finding solutions is an even greater one. The University of Oxford's Africa-Oxford Cancer Consortium (AfrOx), together with the International Atomic Energy Agency (IAEA), is assembling some of the world's most prominent cancer experts and policymakers in London, UK, on 10-11 May, 2007, to take up the challenge. Cancer care services in Africa are desperately limited. Life-saving radiotherapy, which is used effectively on more than 50% of cancer patients in the developed world, is available in only 21 of Africa's 53 countries, or to less than 20% of the total population. Lack of resources and basic infrastructure mean that millions of people have no access to cancer screening, early diagnosis, treatment or palliative care. Moreover, nearly 45% of cancer deaths in Africa are due to rampant viral infection, poor nutrition and widespread tobacco use. 'Many lives in Africa could be saved through prevention strategies and investments in comprehensive cancer control,' says Massoud Samiei, Head of the IAEA's Programme of Action for Cancer Therapy (PACT). 'PACT seeks to mobilize new resources and enable African countries to expand radiotherapy and cancer care in a sustainable manner.' The Cancer Control in Africa meeting will focus on Africa's deepening cancer crisis and develop strategies for much-needed national cancer control programmes. It will also act as a forum for cancer experts and health policymakers to evaluate priorities, guided by needs and available resources. By holding the meeting in London, the organizers hope to place the African problem at the forefront of the global health agenda and to enlist support and new funding from European governments to fight cancer in Africa through joint international programmes. 'We have a timely opportunity to

  6. London forum targets Africa's cancer crisis

    International Nuclear Information System (INIS)

    2007-01-01

    Full text: Africa stands on the brink of a cancer epidemic, with more than a million new cases a year by 2020. Raising awareness of the threat is one of the biggest challenges facing the global health community today. Finding solutions is an even greater one. The University of Oxford's Africa-Oxford Cancer Consortium (AfrOx), together with the International Atomic Energy Agency (IAEA), is assembling some of the world's most prominent cancer experts and policymakers in London, UK, on 10-11 May, 2007, to take up the challenge. Cancer care services in Africa are desperately limited. Life-saving radiotherapy, which is used effectively on more than 50% of cancer patients in the developed world, is available in only 21 of Africa's 53 countries, or to less than 20% of the total population. Lack of resources and basic infrastructure mean that millions of people have no access to cancer screening, early diagnosis, treatment or palliative care. Moreover, nearly 45% of cancer deaths in Africa are due to rampant viral infection, poor nutrition and widespread tobacco use. 'Many lives in Africa could be saved through prevention strategies and investments in comprehensive cancer control,' says Massoud Samiei, Head of the IAEA's Programme of Action for Cancer Therapy (PACT). 'PACT seeks to mobilize new resources and enable African countries to expand radiotherapy and cancer care in a sustainable manner.' The Cancer Control in Africa meeting will focus on Africa's deepening cancer crisis and develop strategies for much-needed national cancer control programmes. It will also act as a forum for cancer experts and health policymakers to evaluate priorities, guided by needs and available resources. By holding the meeting in London, the organizers hope to place the African problem at the forefront of the global health agenda and to enlist support and new funding from European governments to fight cancer in Africa through joint international programmes. 'We have a timely opportunity to

  7. Gold Nanoconstructs for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

    Science.gov (United States)

    Coughlin, Andrew James

    Cancer accounts for nearly 1 out of every 4 deaths in the United States, and because conventional treatments are limited by morbidity and off-target toxicities, improvements in cancer management are needed. This thesis further develops nanoparticle-assisted photothermal therapy (NAPT) as a viable treatment option for cancer patients. NAPT enables localized ablation of disease because heat generation only occurs where tissue permissive near-infrared (NIR) light and absorbing nanoparticles are combined, leaving surrounding normal tissue unharmed. Two principle approaches were investigated to improve the specificity of this technique: multimodal imaging and molecular targeting. Multimodal imaging affords the ability to guide NIR laser application for site-specific NAPT and more holistic characterization of disease by combining the advantages of several diagnostic technologies. Towards the goal of image-guided NAPT, gadolinium-conjugated gold-silica nanoshells were engineered and demonstrated to enhance imaging contrast across a range of diagnostic modes, including T1-weighted magnetic resonance imaging, X-Ray, optical coherence tomography, reflective confocal microscopy, and two-photon luminescence in vitro as well as within an animal tumor model. Additionally, the nanoparticle conjugates were shown to effectively convert NIR light to heat for applications in photothermal therapy. Therefore, the broad utility of gadolinium-nanoshells for anatomic localization of tissue lesions, molecular characterization of malignancy, and mediators of ablation was established. Molecular targeting strategies may also improve NAPT by promoting nanoparticle uptake and retention within tumors and enhancing specificity when malignant and normal tissue interdigitate. Here, ephrinA1 protein ligands were conjugated to nanoshell surfaces for particle homing to overexpressed EphA2 receptors on prostate cancer cells. In vitro, successful targeting and subsequent photothermal ablation of

  8. Podoplanin - an emerging cancer biomarker and therapeutic target.

    Science.gov (United States)

    Krishnan, Harini; Rayes, Julie; Miyashita, Tomoyuki; Ishii, Genichiro; Retzbach, Edward P; Sheehan, Stephanie A; Takemoto, Ai; Chang, Yao-Wen; Yoneda, Kazue; Asai, Jun; Jensen, Lasse; Chalise, Lushun; Natsume, Atsushi; Goldberg, Gary S

    2018-03-25

    Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts (CAFs), and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition (EMT), migration, invasion, metastasis, and inflammation. Antibodies, CAR-T cells, biologics, and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer including glioma, squamous cell carcinoma, mesothelioma, and melanoma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Targeting Prostate Cancer with Multifunctional Nanoparticles

    Science.gov (United States)

    2015-10-01

    claudin-3 and claudin-4 are expressed in subsets of aggressive prostate cancer. Finally, we produced our first two batches of nanoparticles during year...1 and we were able to show that these nanoparticles bind to prostate cancer cells. 15. SUBJECT TERMS Prostate cancer, superparamagnetic iron oxide...degradable polymer that is approved by the FDA, and is used in the development of our nanoparticle system. Our nanoparticles encapsulate

  10. Cellular Imaging | Center for Cancer Research

    Science.gov (United States)

    Innovative imaging methods developed and refined within CCR revealed atomic-level structures of biological molecules and unveiled dynamic views of a cell’s interior that are driving the design of new treatments and diagnostics for cancer.

  11. New approaches to image thyroid cancer cells and microenvironment

    International Nuclear Information System (INIS)

    Galli, F.; Iodice, V.; Signore, A.; Lauri, C.

    2015-01-01

    Poorly differentiated thyroid cancer (PDTC) and undifferentiated thyroid cancer (UDTC) are still life-threatening pathologies, because of the lack of well-established diagnostic and therapeutic approaches. In the past, many attempts have been made to develop radiopharmaceutical to diagnose or treat radioactive iodine (RAI)-refractory metastases or recurrences, with limited results. Indeed, it was not possible to find a specific and over expressed marker to be used as target of radiopharmaceuticals or targeted therapies. Nowadays, with novel advances in the field of tumor microenvironment, many new markers are available to be used as suitable targets for targeted therapies interfering with signalling pathways of cells involved in the mechanisms that favour tumor growth and metastatization. This opened new perspective in the use of radiopharmaceuticals targeting components of tumor microenvironment for early diagnosis, pre-operative staging or therapy planning and follow up with targeted drugs. In the present review we present the state of novel approaches to image thyroid cancer and its microenvironment, focusing on RAI-refractory thyroid cancer as a real clinical problem to be solved.

  12. Virus-Targeted Therapeutic for Breast Cancer

    National Research Council Canada - National Science Library

    Faller, Douglas

    1997-01-01

    .... Our approach initially involves investigation of EBV sequences in breast cancer cell lines and specimens, determination of whether treatment with Arginine Butyrate will induce the viral thymidine...

  13. Targeted delivery of cancer-specific multimodal contrast agents for intraoperative detection of tumor boundaries and therapeutic margins

    Science.gov (United States)

    Xu, Ronald X.; Xu, Jeff S.; Huang, Jiwei; Tweedle, Michael F.; Schmidt, Carl; Povoski, Stephen P.; Martin, Edward W.

    2010-02-01

    Background: Accurate assessment of tumor boundaries and intraoperative detection of therapeutic margins are important oncologic principles for minimal recurrence rates and improved long-term outcomes. However, many existing cancer imaging tools are based on preoperative image acquisition and do not provide real-time intraoperative information that supports critical decision-making in the operating room. Method: Poly lactic-co-glycolic acid (PLGA) microbubbles (MBs) and nanobubbles (NBs) were synthesized by a modified double emulsion method. The MB and NB surfaces were conjugated with CC49 antibody to target TAG-72 antigen, a human glycoprotein complex expressed in many epithelial-derived cancers. Multiple imaging agents were encapsulated in MBs and NBs for multimodal imaging. Both one-step and multi-step cancer targeting strategies were explored. Active MBs/NBs were also fabricated for therapeutic margin assessment in cancer ablation therapies. Results: The multimodal contrast agents and the cancer-targeting strategies were tested on tissue simulating phantoms, LS174 colon cancer cell cultures, and cancer xenograft nude mice. Concurrent multimodal imaging was demonstrated using fluorescence and ultrasound imaging modalities. Technical feasibility of using active MBs and portable imaging tools such as ultrasound for intraoperative therapeutic margin assessment was demonstrated in a biological tissue model. Conclusion: The cancer-specific multimodal contrast agents described in this paper have the potential for intraoperative detection of tumor boundaries and therapeutic margins.

  14. Moving Target Information Extraction Based on Single Satellite Image

    Directory of Open Access Journals (Sweden)

    ZHAO Shihu

    2015-03-01

    Full Text Available The spatial and time variant effects in high resolution satellite push broom imaging are analyzed. A spatial and time variant imaging model is established. A moving target information extraction method is proposed based on a single satellite remote sensing image. The experiment computes two airplanes' flying speed using ZY-3 multispectral image and proves the validity of spatial and time variant model and moving information extracting method.

  15. 3-D Target Location from Stereoscopic SAR Images

    Energy Technology Data Exchange (ETDEWEB)

    DOERRY,ARMIN W.

    1999-10-01

    SAR range-Doppler images are inherently 2-dimensional. Targets with a height offset lay over onto offset range and azimuth locations. Just which image locations are laid upon depends on the imaging geometry, including depression angle, squint angle, and target bearing. This is the well known layover phenomenon. Images formed with different aperture geometries will exhibit different layover characteristics. These differences can be exploited to ascertain target height information, in a stereoscopic manner. Depending on the imaging geometries, height accuracy can be on the order of horizontal position accuracies, thereby rivaling the best IFSAR capabilities in fine resolution SAR images. All that is required for this to work are two distinct passes with suitably different geometries from any plain old SAR.

  16. Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

    Science.gov (United States)

    Mahajan, A; Goh, V; Basu, S; Vaish, R; Weeks, A J; Thakur, M H; Cook, G J

    2015-10-01

    Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure-function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [(18)F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed "theranostics". Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  17. Imaging biomarker roadmap for cancer studies

    NARCIS (Netherlands)

    O'Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; Desouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, J. R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid G.; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel B.; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and

  18. Imaging strategy in differentiated thyroid cancer

    NARCIS (Netherlands)

    Phan, Thi Thanh Ha

    2007-01-01

    This thesis focuses on clinical dilemmas, which the clinician faces in the management of patients with differentiated thyroid cancer (DTC) with a specific emphasis on the role of current and new diagnostic imaging. Thyroid cancer is a rare disease, but it is the most common endocrine malignancy of

  19. Trastuzumab-conjugated liposome-coated fluorescent magnetic nanoparticles to target breast cancer.

    Science.gov (United States)

    Jang, Mijung; Yoon, Young Il; Kwon, Yong Soo; Yoon, Tae-Jong; Lee, Hak Jong; Hwang, Sung Il; Yun, Bo La; Kim, Sun Mi

    2014-01-01

    To synthesize mesoporous silica-core-shell magnetic nanoparticles (MNPs) encapsulated by liposomes (Lipo [MNP@m-SiO2]) in order to enhance their stability, allow them to be used in any buffer solution, and to produce trastuzumab-conjugated (Lipo[MNP@m-SiO2]-Her2Ab) nanoparticles to be utilized in vitro for the targeting of breast cancer. The physiochemical characteristics of Lipo[MNP@m-SiO2] were assessed in terms of size, morphological features, and in vitro safety. The multimodal imaging properties of the organic dye incorporated into Lipo[MNP@m-SiO2] were assessed with both in vitro fluorescence and MR imaging. The specific targeting ability of trastuzumab (Her2/neu antibody, Herceptin®)-conjugated Lipo[MNP@m-SiO2] for Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR imaging. We obtained uniformly-sized and evenly distributed Lipo[MNP@m-SiO2] that demonstrated biological stability, while not disrupting cell viability. Her2/neu-positive breast cancer cell targeting by trastuzumab-conjugated Lipo[MNP@m-SiO2] was observed by in vitro fluorescence and MR imaging. Trastuzumab-conjugated Lipo[MNP@m-SiO2] is a potential treatment tool for targeted drug delivery in Her2/neu-positive breast cancer.

  20. Transtuzumab-conjugated liposome-coated fluorscent magnetic namoparticles to target breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Mi Jung; Lee, Hak Jong; Hwang, Sung Il; Yun, Bo La; Kim, Sun Mi [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Yoon, Young Il; Kwon, Yong Soo [Nanoimaging and Therapy Research Center, Institute of Nanoconvergence, Advanced Institutes of Convergence Technology, Seoul National University, Suwon (Korea, Republic of); Yoon, Tae Jong [NanoBio Materials Chemistry Lab., Dept. of Applied Bioscience, CHA University, Pocheon (Korea, Republic of)

    2014-08-15

    To synthesize mesoporous silica-core-shell magnetic nanoparticles (MNPs) encapsulated by liposomes (Lipo [MNPm-SiO{sub 2}]) in order to enhance their stability, allow them to be used in any buffer solution, and to produce trastuzumab-conjugated (Lipo[MNPm-SiO{sub 2}]-Her2Ab) nanoparticles to be utilized in vitro for the targeting of breast cancer. The physiochemical characteristics of Lipo[MNPm-SiO{sub 2}] were assessed in terms of size, morphological features, and in vitro safety. The multimodal imaging properties of the organic dye incorporated into Lipo[MNPm-SiO{sub 2}] were assessed with both in vitro fluorescence and MR imaging. The specific targeting ability of trastuzumab (Her2/neu antibody, Herceptin)-conjugated Lipo[MNPm-SiO{sub 2}] for Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR imaging. We obtained uniformly-sized and evenly distributed Lipo[MNPm-SiO{sub 2}] that demonstrated biological stability, while not disrupting cell viability. Her2/neu-positive breast cancer cell targeting by trastuzumab-conjugated Lipo[MNPm-SiO{sub 2}] was observed by in vitro fluorescence and MR imaging. Trastuzumab-conjugated Lipo[MNPm-SiO{sub 2}] is a potential treatment tool for targeted drug delivery in Her2/neu-positive breast cancer.

  1. Mechanoresponsive stem cells to target cancer metastases through biophysical cues.

    Science.gov (United States)

    Liu, Linan; Zhang, Shirley X; Liao, Wenbin; Farhoodi, Henry P; Wong, Chi W; Chen, Claire C; Ségaliny, Aude I; Chacko, Jenu V; Nguyen, Lily P; Lu, Mengrou; Polovin, George; Pone, Egest J; Downing, Timothy L; Lawson, Devon A; Digman, Michelle A; Zhao, Weian

    2017-07-26

    Despite decades of effort, little progress has been made to improve the treatment of cancer metastases. To leverage the central role of the mechanoenvironment in cancer metastasis, we present a mechanoresponsive cell system (MRCS) to selectively identify and treat cancer metastases by targeting the specific biophysical cues in the tumor niche in vivo. Our MRCS uses mechanosensitive promoter-driven mesenchymal stem cell (MSC)-based vectors, which selectively home to and target cancer metastases in response to specific mechanical cues to deliver therapeutics to effectively kill cancer cells, as demonstrated in a metastatic breast cancer mouse model. Our data suggest a strong correlation between collagen cross-linking and increased tissue stiffness at the metastatic sites, where our MRCS is specifically activated by the specific cancer-associated mechano-cues. MRCS has markedly reduced deleterious effects compared to MSCs constitutively expressing therapeutics. MRCS indicates that biophysical cues, specifically matrix stiffness, are appealing targets for cancer treatment due to their long persistence in the body (measured in years), making them refractory to the development of resistance to treatment. Our MRCS can serve as a platform for future diagnostics and therapies targeting aberrant tissue stiffness in conditions such as cancer and fibrotic diseases, and it should help to elucidate mechanobiology and reveal what cells "feel" in the microenvironment in vivo. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  2. Inflammation as target in cancer therapy.

    Czech Academy of Sciences Publication Activity Database

    Marelli, G.; Sica, A.; Vannucci, Luca; Allavena, P.

    2017-01-01

    Roč. 35, August 2017 (2017), s. 57-65 ISSN 1471-4892 Institutional support: RVO:61388971 Keywords : cancer therapy * cancer-promoting inflammation * Tumour-Associated Macrophages Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 5.363, year: 2016

  3. Diagnostic Imaging of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Kemal Kara

    2012-12-01

    Full Text Available Lung cancer is the most common cause of cancer related death in men and women. It is frequently seen among men than in women and male-female ratio is 1.5:1. Common epidemiological factors that increase risk of lung cancer is smoking. Early age to start smoking, high number of smoking cigarettes per a day and depth of inhalation increase risk of lung cancer. 25% of patients with lung cancer are nonsmokers that passively exposed to cigarette smoke. Occupational exposure to substances such as asbestos, arsenic, nickel, beryllium, mustard gas increases the risk of lung cancer. The well defined risk factor is exposure to asbestos. In addition advanced age, diffuse pulmonary fibrosis, chronic obstructive pulmonary disease (COPD and genetic predisposition are the risk factors that increases lung cancer. [TAF Prev Med Bull 2012; 11(6.000: 749-756

  4. Targeted nanodiamonds as phenotype-specific photoacoustic contrast agents for breast cancer.

    Science.gov (United States)

    Zhang, Ti; Cui, Huizhong; Fang, Chia-Yi; Cheng, Kun; Yang, Xinmai; Chang, Huan-Cheng; Forrest, M Laird

    2015-03-01

    The aim is to develop irradiated nanodiamonds (INDs) as a molecularly targeted contrast agent for high-resolution and phenotype-specific detection of breast cancer with photoacoustic (PA) imaging. The surface of acid treated radiation-damaged nanodiamonds was grafted with PEG to improve its stability and circulation time in blood, followed by conjugation to an anti-HER2 peptide with a final nanoparticle size of approximately 92 nm. Immunocompetent mice bearing orthotopic HER2-positive or negative tumors were administered INDs and PA imaged using an 820-nm near-infrared laser. PA images demonstrated that INDs accumulate in tumors and completely delineated the entire tumor within 10 h. HER2 targeting significantly enhanced imaging of HER2-positive tumors. Pathological examination demonstrated INDs are nontoxic. PA technology is adaptable to low-cost bedside medicine, and with new contrast agents described herein, PA can achieve high-resolution (sub-mm) and phenotype-specific monitoring of cancer growth.

  5. Photosensitizer-conjugated tryptophan-containing peptide ligands as new dual-targeted theranostics for cancers.

    Science.gov (United States)

    Kim, Jisu; Chae, Jihyun; Kim, Jun Soo; Goh, Sung-Ho; Choi, Yongdoo

    2016-11-20

    Here we report that new dual-targeted theranostic anti-cancer agents can be produced by simple conjugation of photosensitizers with tryptophan-containing peptide ligands via cyclic disulfide linkages. In the proof-of-concept study, photosensitizers conjugated with EGFR-targeting peptide GE11 (C-EGFR) were in close proximity with tryptophan residues in the conjugate, resulting in quenching of its fluorescence and singlet oxygen generation. C-EGFR specifically binds to target receptors on the cancer cell surface, after which it is internalized via receptor-mediated endocytosis. Intracellular cleavage of cyclic disulfide bonds allows separation of the photosensitizers from the tryptophan residue, after which they emit near-infrared (NIR) fluorescence and produce a phototoxic effect in the target cells. This strategy enabled us to accomplish simultaneous real-time NIR fluorescence imaging of EGFR-overexpressing cancer cells with high contrast and selective photodynamic therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Antibody or Antibody Fragments: Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

    Directory of Open Access Journals (Sweden)

    Katerina T. Xenaki

    2017-10-01

    Full Text Available The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody–drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are clearly still necessary. A major factor limiting the efficacy of antibody-targeted cancer therapies may be the incomplete penetration of the antibody or antibody–drug conjugate into the tumor. Incomplete tumor penetration also affects the outcome of molecular imaging, when using such targeting agents. From the injection site until they arrive inside the tumor, targeting molecules are faced with several barriers that impact intratumoral distribution. The primary means of antibody transport inside tumors is based on diffusion. The diffusive penetration inside the tumor is influenced by both antibody properties, such as size and binding affinity, as well as tumor properties, such as microenvironment, vascularization, and targeted antigen availability. Engineering smaller antibody fragments has shown to improve the rate of tumor uptake and intratumoral distribution. However, it is often accompanied by more rapid clearance from the body and in several cases also by inherent destabilization and reduction of the binding affinity of the antibody. In this perspective, we discuss different cancer targeting approaches based on antibodies or their fragments. We carefully consider how their size and binding properties influence their intratumoral uptake and distribution, and how this may affect cancer imaging and therapy of solid tumors.

  7. TCGA bladder cancer study reveals potential drug targets

    Science.gov (United States)

    Investigators with TCGA have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bla

  8. Detecting and Targeting Oncogenic Myc in Breast Cancer

    National Research Council Canada - National Science Library

    Penn, Linda Z

    2007-01-01

    Deregulation of the cellular myc proto-oncogene is one of the strongest activators of tumorigenesis and understanding the target genes regulated by this transcription factor in cancer etiology will...

  9. Targeting a Novel Vector for Breast Cancer Gene Therapy

    National Research Council Canada - National Science Library

    Bzik, David

    2002-01-01

    .... The primary purpose and scope of this IDEA award project is to experimentally examine approaches to safely target the Toxoplasma gondii parasite gene therapy vector to breast cancer tissue using...

  10. Performance Analysis on ISAR Imaging of Space Targets

    Directory of Open Access Journals (Sweden)

    Zhou Yejian

    2017-02-01

    Full Text Available Usually, in traditional Inverse Synthetic Aperture Radar (ISAR systems design and mode selection for space satellite targets, coherent integration gain in azimuth direction hardly can be analyzed, which depends on target’s motion. In this study, we combine the target orbit parameters to determine its motion relative to radar and deduce coherent integration equation in ISAR imaging to realize the selection of imaging intervals based on coherent integration, which can ensure the resolution in azimuth direction. Meanwhile, we analyze the influence of target orbit altitude to echo power and imaging Signal-to-Noise Ratio (SNR that provides a new indicator for space observation ISAR systems design. The result of simulation experiment illustrates that with target orbit altitude increasing, coherent integration gain in azimuth direction of large-angular observation offsets the decreasing of imaging SNR in a degree, which provides a brand-new perspective for space observation ISAR systems and signal processing design.

  11. Targeting SRC Family Kinases in HSP90 in Lung Cancer

    Science.gov (United States)

    2015-10-01

    Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited Targeting SRC Family Kinases and HSP90 in Lung Cancer...COVERED Annual 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting SRC Family Kinases in HSP90 in Lung Cancer 5b. GRANT...AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS Nedd9, Src , HSP90

  12. [Preserving one's self-image despite cancer].

    Science.gov (United States)

    Caltagirone, Aury

    2014-03-01

    Cancer and the side effects of the treatments affect a patient's self-image. The assistance of a personal image consultant and socio-aesthetician can help the patient restore their appearance and become more accepting of themselves. It enables them to be more at ease in their relationships with others and reinforces self-esteem.

  13. Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

    Science.gov (United States)

    Subramaniam, Prasad

    Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on

  14. Targeting cancer stem-like cells in glioblastoma and colorectal cancer through metabolic pathways.

    Science.gov (United States)

    Kahlert, U D; Mooney, S M; Natsumeda, M; Steiger, H-J; Maciaczyk, J

    2017-01-01

    Cancer stem-like cells (CSCs) are thought to be the main cause of tumor occurrence, progression and therapeutic resistance. Strong research efforts in the last decade have led to the development of several tailored approaches to target CSCs with some very promising clinical trials underway; however, until now no anti-CSC therapy has been approved for clinical use. Given the recent improvement in our understanding of how onco-proteins can manipulate cellular metabolic networks to promote tumorigenesis, cancer metabolism research may well lead to innovative strategies to identify novel regulators and downstream mediators of CSC maintenance. Interfering with distinct stages of CSC-associated metabolics may elucidate novel, more efficient strategies to target this highly malignant cell population. Here recent discoveries regarding the metabolic properties attributed to CSCs in glioblastoma (GBM) and malignant colorectal cancer (CRC) were summarized. The association between stem cell markers, the response to hypoxia and other environmental stresses including therapeutic insults as well as developmentally conserved signaling pathways with alterations in cellular bioenergetic networks were also discussed. The recent developments in metabolic imaging to identify CSCs were also summarized. This summary should comprehensively update basic and clinical scientists on the metabolic traits of CSCs in GBM and malignant CRC. © 2016 UICC.

  15. Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

    Science.gov (United States)

    2017-10-01

    since, in the absence of such knowledge, the development of effective therapeutic interventions to target CSCs and prevent cancer progression and...yes) (2) Presentations: a. 2016 Keystone Symposia- Stem Cells & Cancer, Breckenridge, “Epigenetic regulation promotes obesity related breast

  16. Compositions and methods for cancer treatment using targeted carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Jr., Roger G.; Resasco, Daniel E.; Neves, Luis Filipe Ferreira

    2016-11-29

    Compositions for detecting and/or destroying cancer tumors and/or cancer cells via photodynamic therapy are disclosed, as well as methods of use thereof. The compositions comprise a linking protein or peptide attached to or otherwise physically associated with a carbon nanotube to form a targeted protein-carbon nanotube complex.

  17. T-cell target antigens across major gynecologic cancers.

    Science.gov (United States)

    Rodriguez-Garcia, Alba; Minutolo, Nicholas G; Robinson, John M; Powell, Daniel J

    2017-06-01

    Immunotherapies have achieved remarkable success in treating different forms of cancer including melanoma, non-small cell lung carcinoma, bladder cancer, synovial cell sarcoma, and multiple myeloma using immune checkpoint blockade or gene-engineered T-cells. Although gynecologic cancers have not been historically classified as immunogenic tumors, growing evidence has shown that they are in fact able to elicit endogenous antitumor immune responses suggesting that patients with these cancers may benefit from immunotherapy. Modest clinical success has been accomplished in early trials using immunotherapeutic modalities for major gynecologic cancers including ovarian, cervical, and endometrial cancer. Unlike solid cancers with high mutational burdens, or hematologic malignancies where target antigens are expressed homogenously and exclusively by tumor cells, identifying tumor-restricted antigens has been challenging when designing a T-cell targeted therapy for gynecologic tumors. Nevertheless, mounting preclinical and clinical evidence suggests that targeting shared, viral or patient-specific mutated antigens expressed by gynecologic tumors with T-cells may improve patient outcome. Here we review the strengths and weaknesses of targeting these various antigens, as well as provide insight into the future of immunotherapy for gynecologic cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Oncolytic Virotherapy Targeting Lung Cancer Drug Resistance

    Science.gov (United States)

    2013-08-01

    resistant phenotype. Because cisplatin is highly mutagenic, it has an ability to quickly induce genetic changes in cancer cells usually resulting in... Mendelian selection and generation of cells that acquire a permanent resistant phenotype (8). We initially exposed both KLN205 and LLC1 to increasing...multiple epigenetic and genetic changes. Pharmacological reviews 64:706-721. 9. Siegel, R., D. Naishadham, and A. Jemal. 2013. Cancer statistics, 2013

  19. Targeting the Neural Microenvironment in Prostate Cancer

    Science.gov (United States)

    2017-10-01

    lenvatinib, a multikinase inhibitor that inhibits RET, FGFRs, VEGFRs and PDGFRs3. This drug is in the clinic and approved for treatment of advanced thyroid ...hypothesis is correct, treatment of men with lenvatinib may enhance long term treatment outcomes in men with more aggressive disease Fig 7. Lenvatinib... thyroid cancer and other solid tumors, Cancer Treat Rev 2016, 42:47-55 4. Yu W, Feng S, Dakhova O, Creighton CJ, Cai Y, Wang J, Li R, Frolov A, Ayala G

  20. Targeting Autophagy in ALK-Associated Cancers

    Directory of Open Access Journals (Sweden)

    Julie Frentzel

    2017-11-01

    Full Text Available Autophagy is an evolutionarily conserved catabolic process, which is used by the cells for cytoplasmic quality control. This process is induced following different kinds of stresses e.g., metabolic, environmental, or therapeutic, and acts, in this framework, as a cell survival mechanism. However, under certain circumstances, autophagy has been associated with cell death. This duality has been extensively reported in solid and hematological cancers, and has been observed during both tumor development and cancer therapy. As autophagy plays a critical role at the crossroads between cell survival and cell death, its involvement and therapeutic modulation (either activation or inhibition are currently intensively studied in cancer biology, to improve treatments and patient outcomes. Over the last few years, studies have demonstrated the occurrence of autophagy in different Anaplastic Lymphoma Kinase (ALK-associated cancers, notably ALK-positive anaplastic large cell lymphoma (ALCL, non-small cell lung carcinoma (NSCLC, Neuroblastoma (NB, and Rhabdomyosarcoma (RMS. In this review, we will first briefly describe the autophagic process and how it can lead to opposite outcomes in anti-cancer therapies, and we will then focus on what is currently known regarding autophagy in ALK-associated cancers.

  1. Optical Imaging in Breast Cancer Diagnosis: The Next Evolution

    Directory of Open Access Journals (Sweden)

    Michel Herranz

    2012-01-01

    Full Text Available Breast cancer is one of the most common cancers among the population of the Western world. Diagnostic methods include mammography, ultrasound, and magnetic resonance; meanwhile, nuclear medicine techniques have a secondary role, being useful in regional assessment and therapy followup. Optical imaging is a very promising imaging technique that uses near-infrared light to assess optical properties of tissues and is expected to play an important role in breast cancer detection. Optical breast imaging can be performed by intrinsic breast tissue contrast alone (hemoglobin, water, and lipid content or with the use of exogenous fluorescent probes that target specific molecules for breast cancer. Major advantages of optical imaging are that it does not use any radioactive components, very high sensitivity, relatively inexpensive, easily accessible, and the potential to be combined in a multimodal approach with other technologies such as mammography, ultrasound, MRI, and positron emission tomography. Moreover, optical imaging agents could, potentially, be used as “theranostics,” combining the process of diagnosis and therapy.

  2. Metabolic isoenzyme shifts in cancer as potential novel therapeutic targets.

    Science.gov (United States)

    Ononye, S N; Shi, W; Wali, V B; Aktas, B; Jiang, T; Hatzis, C; Pusztai, L

    2014-12-01

    The functional redundancy of metabolic enzyme expression may present a new strategy for developing targeted therapies in cancer. To satisfy the increased metabolic demand required during neoplastic transformations and proliferation, cancer cells may rely on additional isoforms of a metabolic enzyme to satisfy the increased demand for metabolic precursors, which could subsequently render cancer cells more vulnerable to isoform-specific inhibitors. In this review, we provide a survey of common isoenzyme shifts that have been reported to be important in cancer metabolism and link those to metabolic pathways that currently have drugs in various stages of development. This phenomenon suggests a potentially new therapeutic strategy for the treatment of cancer by identifying shifts in the expression of metabolic isoenzymes between cancer and normal cells. We also delineate other putative metabolic isoenzymes that could be targets for novel targeted therapies for cancer. Changes in isoenzyme expression that occur during neoplastic transformations or in response to environmental pressure in cancer cells may result in isoenzyme diversity that may subsequently render cancer cells more vulnerable to isoform-specific inhibitors due to reliance on a single isoform to perform a vital enzymatic function.

  3. Target recognition in passive terahertz image of human body

    Science.gov (United States)

    Zhao, Ran; Zhao, Yuan-meng; Deng, Chao; Zhang, Cun-lin; Li, Yue

    2014-11-01

    THz radiation can penetrate through many nonpolar dielectric materials and can be used for nondestructive/noninvasive sensing and imaging of targets under nonpolar, nonmetallic covers or containers. Thus using THz systems to "see through" concealing barriers (i.e. packaging, corrugated cardboard, clothing) has been proposed as a new security screening method. Objects that can be detected by THz include concealed weapons, explosives, and chemical agents under clothing. Passive THz imaging system can detect THz wave from human body without transmit any electromagnetic wave, and the suspicious objects will become visible because the THz wave is blocked by this items. We can find out whether or not someone is carrying dangerous objects through this image. In this paper, the THz image enhancement, segmentation and contour extraction algorithms were studied to achieve effective target image detection. First, the terahertz images are enhanced and their grayscales are stretched. Then we apply global threshold segmentation to extract the target, and finally the targets are marked on the image. Experimental results showed that the algorithm proposed in this paper can extract and mark targets effectively, so that people can identify suspicious objects under clothing quickly. The algorithm can significantly improve the usefulness of the terahertz security apparatus.

  4. Employing image processing techniques for cancer detection using microarray images.

    Science.gov (United States)

    Dehghan Khalilabad, Nastaran; Hassanpour, Hamid

    2017-02-01

    Microarray technology is a powerful genomic tool for simultaneously studying and analyzing the behavior of thousands of genes. The analysis of images obtained from this technology plays a critical role in the detection and treatment of diseases. The aim of the current study is to develop an automated system for analyzing data from microarray images in order to detect cancerous cases. The proposed system consists of three main phases, namely image processing, data mining, and the detection of the disease. The image processing phase performs operations such as refining image rotation, gridding (locating genes) and extracting raw data from images the data mining includes normalizing the extracted data and selecting the more effective genes. Finally, via the extracted data, cancerous cell is recognized. To evaluate the performance of the proposed system, microarray database is employed which includes Breast cancer, Myeloid Leukemia and Lymphomas from the Stanford Microarray Database. The results indicate that the proposed system is able to identify the type of cancer from the data set with an accuracy of 95.45%, 94.11%, and 100%, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Feature-aided multiple target tracking in the image plane

    Science.gov (United States)

    Brown, Andrew P.; Sullivan, Kevin J.; Miller, David J.

    2006-05-01

    Vast quantities of EO and IR data are collected on airborne platforms (manned and unmanned) and terrestrial platforms (including fixed installations, e.g., at street intersections), and can be exploited to aid in the global war on terrorism. However, intelligent preprocessing is required to enable operator efficiency and to provide commanders with actionable target information. To this end, we have developed an image plane tracker which automatically detects and tracks multiple targets in image sequences using both motion and feature information. The effects of platform and camera motion are compensated via image registration, and a novel change detection algorithm is applied for accurate moving target detection. The contiguous pixel blob on each moving target is segmented for use in target feature extraction and model learning. Feature-based target location measurements are used for tracking through move-stop-move maneuvers, close target spacing, and occlusion. Effective clutter suppression is achieved using joint probabilistic data association (JPDA), and confirmed target tracks are indicated for further processing or operator review. In this paper we describe the algorithms implemented in the image plane tracker and present performance results obtained with video clips from the DARPA VIVID program data collection and from a miniature unmanned aerial vehicle (UAV) flight.

  6. Targeted Gene Therapy for Breast Cancer

    Science.gov (United States)

    1999-08-01

    or immunotoxin therapy, natural vector-host tropisms must be altered. Recent improvements in monoclonal antibody (mAb) engineering have expanded the...endocytosis. To achieve targeted gene therapy or immunotoxin therapy, natural vector-host tropisms must be altered. Recent improvements in monoclonal...trafficking of monoclonal antibody- antigen to an endolysosomal pathway is important. After altering targeting specificities, prokaryotic and plant

  7. Ovarian Cancer Stem Cells: A New Target for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Qinglei Zhan

    2013-01-01

    Full Text Available Ovarian cancer is a highly lethal disease among all gynecologic malignancies and is the fifth leading cause of cancer-related death in women. Although the standard combination of surgery and chemotherapy was initially effective in patients with ovarian cancer, disease relapse commonly occurred due to the generation of chemoresistance. It has been reported that cancer stem cells (CSCs are involved in drug resistance and cancer recurrence. Over the past decades, increasing studies have been done to identify CSCs from human ovarian cancer cells. The present paper will summarize different investigations on ovarian CSCs, including isolation, mechanisms of chemoresistance, and therapeutic approaches. Although there are still numerous challenges to translate basic research to clinical applications, understanding the molecular details of CSCs is essential for developing effective strategies to prevent ovarian cancer and its recurrence.

  8. Antibody-targeted thrombus imaging and thrombolysis

    International Nuclear Information System (INIS)

    Wu Guoxin; Ruan Changgeng

    1993-05-01

    In respect of thrombus imaging, the femoral arterial or venous thrombus model was prepared in dogs and imaged with single photon emission computerized tomography (SPECT). After 4 hours of injection of 131 I-SZ-51 the radioactivity ratio between thrombus and blood (T/B) was 18 : 1 and 8 : 1 for arterial and venous thrombus respectively. The result conformed with the T/B ratio of the removed thrombus and blood after 24 hours of injection of radiotracer. It indicates that the McAb SZ-51 has a great potential to bind with thrombus. In respect of thrombolysis, the Fab(fragment, antigen-binding) fragment of McAb SZ-51 was chemically conjugated of urokinase (UK) by the disulfide-linking reagent SPDP and 2-iminothiolane. The resulting conjugate was 3 to 5 times as potent as UK in vitro in human platelet-rich plasma assay. The increase of fibrinolytic potency was accompanied by a decrease of consumption of plasminogen and fibrinogen. It shows that the increase of potency is the result of selectivity increase

  9. Targeting the Synthetic Essential Kinases of Breast Cancers

    Science.gov (United States)

    2016-05-01

    kinases in mitosis and tumorigenesis. Mol Cancer Res 2007, 5(1):1-10. 12. Kufer TA, Sillje HH, Korner R, Gruss OJ, Meraldi P, Nigg EA: Human TPX2 is...AWARD NUMBER: W81XWH-15-1-0027 TITLE: Targeting the synthetic essential kinases of breast cancers PRINCIPAL INVESTIGATOR: Jen-Tsan...Targeting the synthetic essential kinases of breast cancers 5b. GRANT NUMBER W81XWH-15-1-0027 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT

  10. Targeting post-translational modifications of histones for cancer therapy.

    Science.gov (United States)

    Hsu, Y-C; Hsieh, Y-H; Liao, C-C; Chong, L-W; Lee, C-Y; Yu, Y-L; Chou, R-H

    2015-10-30

    Post-translational modifications (PTMs) on histones including acetylation, methylation, phosphorylation, citrullination, ubiquitination, ADP ribosylation, and sumoylation, play important roles in different biological events including chromatin dynamics, DNA replication, and transcriptional regulation. Aberrant histones PTMs leads to abnormal gene expression and uncontrolled cell proliferation, followed by development of cancers. Therefore, targeting the enzymes required for specific histone PTMs holds a lot of potential for cancer treatment. In this review article, we retrospect the latest studies in the regulations of acetylation, methylation, and phosphorylation of histones. We also summarize inhibitors/drugs that target these modifications for cancer treatment.

  11. Skp2 is a promising therapeutic target in breast cancer

    Directory of Open Access Journals (Sweden)

    Zhiwei eWang

    2012-01-01

    Full Text Available Breast cancer is the most common type of cancer among American women, and remains the second leading cause of cancer-related death for female in the United States. It has been known that several signaling pathways and various factors play critical roles in the development and progression of breast cancer, such as estrogen receptor, Notch, PTEN, Her2, PI3K/Akt, BRCA1 and BRCA2. Emerging evidence has shown that the F-box protein Skp2 (S-phase kinase associated protein 2 also plays an important role in the pathogenesis of breast cancer. Therefore, in this brief review, we summarize the novel functions of Skp2 in the pathogenesis of breast cancer. Moreover, we provide further evidence regarding the state of our knowledge toward the development of novel Skp2 inhibitors especially natural chemopreventive agents as targeted approach for the prevention and/or treatment of breast cancer.

  12. Multiparametric MR imaging of prostate cancer foci: assessing the detectability and localizability of Gleason 7 peripheral zone cancers based on image contrasts

    Science.gov (United States)

    Gibson, Eli; Gaed, Mena; Hrinivich, Thomas; Gómez, José A.; Moussa, Madeleine; Romagnoli, Cesare; Mandel, Jonathan; Bastian-Jordan, Matthew; Cool, Derek W.; Ghoul, Suha; Pautler, Stephen E.; Chin, Joseph L.; Crukley, Cathie; Bauman, Glenn S.; Fenster, Aaron; Ward, Aaron D.

    2014-03-01

    Purpose: Multiparametric magnetic resonance imaging (MPMRI) supports detection and staging of prostate cancer, but the image characteristics needed for tumor boundary delineation to support focal therapy have not been widely investigated. We quantified the detectability (image contrast between tumor and non-cancerous contralateral tissue) and the localizability (image contrast between tumor and non-cancerous neighboring tissue) of Gleason score 7 (GS7) peripheral zone (PZ) tumors on MPMRI using tumor contours mapped from histology using accurate 2D-3D registration. Methods: MPMRI [comprising T2-weighted (T2W), dynamic-contrast-enhanced (DCE), apparent diffusion coefficient (ADC) and contrast transfer coefficient images] and post-prostatectomy digitized histology images were acquired for 6 subjects. Histology contouring and grading (approved by a genitourinary pathologist) identified 7 GS7 PZ tumors. Contours were mapped to MPMRI images using semi-automated registration algorithms (combined target registration error: 2 mm). For each focus, three measurements of mean +/- standard deviation of image intensity were taken on each image: tumor tissue (mT+/-sT), non-cancerous PZ tissue Results: T2W images showed the strongest detectability, although detectability |D|>=1 was observed on either ADC or DCE images, or both, for all foci. Localizability on all modalities was variable; however, ADC images showed localizability |L|>=1 for 3 foci. Conclusions: Delineation of GS7 PZ tumors on individual MPMRI images faces challenges; however, images may contain complementary information, suggesting a role for fusion of information across MPMRI images for delineation.

  13. Design and implementation of typical target image database system

    International Nuclear Information System (INIS)

    Qin Kai; Zhao Yingjun

    2010-01-01

    It is necessary to provide essential background data and thematic data timely in image processing and application. In fact, application is an integrating and analyzing procedure with different kinds of data. In this paper, the authors describe an image database system which classifies, stores, manages and analyzes database of different types, such as image database, vector database, spatial database, spatial target characteristics database, its design and structure. (authors)

  14. Targeting of the P2X7 receptor in pancreatic cancer and stellate cells

    DEFF Research Database (Denmark)

    Giannuzzo, Andrea; Saccomano, Mara; Napp, Joanna

    2016-01-01

    The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which...... into nude mice and tumour growth was followed noninvasively by bioluminescence imaging. AZ10606120-treated mice showed reduced bioluminescence compared to saline-treated mice. Immunohistochemical analysis confirmed P2X7R expression in cancer and PSC cells, and in metaplastic/neoplastic acinar and duct...

  15. Enzyme targeting strategies for prevention and treatment of cancer: Implications for cancer therapy.

    Science.gov (United States)

    Baig, Mohammad Hassan; Adil, Mohd; Khan, Rosina; Dhadi, Surendar; Ahmad, Khurshid; Rabbani, Gulam; Bashir, Tufail; Imran, Mohammad Azhar; Husain, Fohad Mabood; Lee, Eun Ju; Kamal, Mohammad Amjad; Choi, Inho

    2017-12-14

    Extensive growth of cancer in humans is a major cause of death. Numerous studies are being conducted to improve the early diagnosis, prevention, and treatment of cancer. Recent technological advancements in medical science and research indicate molecular target therapy holds much promise in cancer treatment. In the past, therapeutic and diagnostic targeting of non-glycolytic and glycolytic enzymes in cancer have been successful, and discoveries of biomarker enzymes in cancer hold promise for therapeutic treatments. In this review, we discuss the roles of several cancer-associated enzymes that could potentially act as therapeutic targets, and place special focus on non-glycolytic and glycolytic enzymes. This review indicates that the targeting of metabolic signaling offers a promising means of developing novel anti-cancer therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Head and neck cancer imaging. 2. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Hermans, Robert (ed.) [University Hospital, Leuven (Belgium). Dept. of Radiology

    2012-07-01

    Imaging is crucial in the multidisciplinary approach to head and neck cancer management. The rapid technological development of recent years makes it necessary for all members of the multidisciplinary team to understand the potential applications, limitations, and advantages of existing and evolving imaging technologies. It is equally important that the radiologist has sufficient clinical background knowledge to understand the clinical significance of imaging findings. This book provides an overview of the findings obtained using different imaging techniques during the evaluation of head and neck neoplasms, both before and after therapy. All anatomic areas in the head and neck are covered, and the impact of imaging on patient management is discussed in detail. The authors are recognized experts in the field, and numerous high-quality images are included. This second edition provides information on the latest imaging developments in this area, including the application of PET-CT and diffusion-weighted magnetic resonance imaging.

  17. Targeting Apolipoproteins in Magnetic Resonance Imaging

    Science.gov (United States)

    Sriram, Renuka; Lagerstedt, Jens O.; Samardzic, Haris; Kreutzer, Ulrike; Petrolova, Jitka; Xie, Hongtao; Kaysen, George A.; Voss, John C.; Desreux, Jean F.; Jue, Thomas

    Maintaining normal physiological homeostasis depends upon a coordinated metabolism of both water-soluble and -insoluble substrates. In humans the body derives these molecules — such as glucose, amino acids, and fatty acids — from complex food matter. Water-soluble substrates can circulate readily in blood, while water-insoluble molecules — such as fatty acid, triacylglycerol, and cholesterol — require ampiphathic carriers to transport them from the site of biosynthesis (liver and intestine) to the target tissue. For fatty acid, albumin serves as the major transporter. For triacylglycerol and cholesterol, however, macromolecular complexes aggregate the hydrophobic molecules into the core and cover the surface with amphiphatic proteins and phospholipids to solubilize the particles in the lymphatic and circulatory systems. These macromolecules belong to a class of proteins, plasma lipoproteins, with specific functions and cellular targets. In the clinic these lipoproteins prognosticate the risk of cardiovascular disease (CVD). Lipoproteins divide usually into five major types: chylomicron, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Each lipoprotein type exhibits characteristic density, size, and composition. As implied in the name, the density varies from the low-density chylomicron (<0.95 g/ml) to the high-density HDL (1.2 g/ml). Size also varies. The chylomicron has the largest diameter (75-1,200 nm), and HDL has the smallest (5-12 nm). The physical property variation arises from each lipoprotein's distinct composition. In a chylomicron, cholesterol, triacylglycerol, and phospholipid predominate and constitute about 90% of the particle. Protein constitutes only about 10%. In contrast, the smaller HDL has less cholesterol, triacylglycerol, and phospholipid (65% of the particle) but more protein (over 30%).

  18. Advances of Molecular Targeted Therapy in Squamous Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Li MA

    2013-12-01

    Full Text Available Squamous cell lung cancer (SQCLC is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR inhibitors or anaplastic lymphoma kinase (ALK inhibitors that show exquisite activity in lungadenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1 gene, the discoidin domain receptor 2 (DDR2 gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lungcancer assessing the value of novel therapeutics addressing these targets.

  19. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

    Science.gov (United States)

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS) are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concentration. ROS facilitates carcinogenesis and cancer progression with mild-to-moderate elevated levels, while excessive ROS damages cancer cells dramatically and leads to cell death. Based on the recent knowledge, either promoting ROS generation to increase the concentration of ROS with extremely high levels or enhancing ROS scavenging ability to decrease ROS levels may benefit the treatment of pancreatic cancer. However, when faced with oxidative stress, the antioxidant programs of cancer cells have been activated to help cancer cells to survive in the adverse condition. Furthermore, ROS signaling and antioxidant programs play the vital roles in the progression of pancreatic cancer and in the response to cancer treatment. Eventually, it may be the novel target for various strategies and drugs to modulate ROS levels in pancreatic cancer therapy. PMID:26881012

  20. [Body image disorder in 100 Tunisian female breast cancer patients].

    Science.gov (United States)

    Faten, Ellouze; Nader, Marrakchi; Raies, Hend; Sana, Masmoudi; Amel, Mezlini; Fadhel, M'rad Mohamed

    2018-03-07

    This study aimed at tracking the prevalence of body image disorder in a population of Tunisian women followed for breast cancer and the factors associated with it. The cross-sectional study was conducted at Salah-Azaiez Institute in Tunis, over a period of four months. One hundred outpatients followed for confirmed breast cancer were recruited. The questionnaire targeted the women's sexuality and their couple relationships, along with their socio-demographic, clinical, and therapeutic characteristics. The scales used were BIS, HADS, and FSFI. The prevalence of body image disorder according to BIS was 45% with an average of 11.5±11.2 among the interrogated patients, 24.7% of which reported an alteration in their couple relationships and 47% in their sexual relations. In univariate analysis, body image disorder was associated with family support, change in couple relationship, depression and anxiety. Body image disorder and sexual dysfunction were interrelated: each of them fostered the prevalence of the other. Multivariate analysis showed that occupational activity was an independent predictor and the absence of anxiety an independent protective factor. Body image disorder was an independent predictive factor of depression and anxiety. The quality of couple relation and sexuality, along with the impact of the patient's surrounding are decisive for the protection or alteration of her body image. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  1. Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids.

    Science.gov (United States)

    Ngwa, Wilfred; Kumar, Rajiv; Moreau, Michele; Dabney, Raymond; Herman, Allen

    2017-01-01

    Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones) can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous ("sea") routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

  2. Targeting therapy-resistant cancer stem cells by hyperthermia

    DEFF Research Database (Denmark)

    Oei, A L; Vriend, L E M; Krawczyk, P M

    2017-01-01

    Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells...... (CSCs), is considered to be of particular significance for tumour initiation, progression and metastasis. CSCs are considered in particular to be therapy-resistant and may drive disease recurrence, which positions CSCs in the focus of anti-cancer research, but successful CSC-targeting therapies...... are limited. Here, we argue that hyperthermia - a therapeutic approach based on local heating of a tumour - is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising...

  3. Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

    Directory of Open Access Journals (Sweden)

    Wilfred Ngwa

    2017-09-01

    Full Text Available Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH (air versus traditional intravenous (“sea” routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

  4. Target Image Matching Algorithm Based on Binocular CCD Ranging

    Directory of Open Access Journals (Sweden)

    Dongming Li

    2014-01-01

    Full Text Available This paper proposed target image in a subpixel level matching algorithm for binocular CCD ranging, which is based on the principle of binocular CCD ranging. In the paper, firstly, we introduced the ranging principle of the binocular ranging system and deduced a binocular parallax formula. Secondly, we deduced the algorithm which was named improved cross-correlation matching algorithm and cubic surface fitting algorithm for target images matched, and it could achieve a subpixel level matching for binocular CCD ranging images. Lastly, through experiment we have analyzed and verified the actual CCD ranging images, then analyzed the errors of the experimental results and corrected the formula of calculating system errors. Experimental results showed that the actual measurement accuracy of a target within 3 km was higher than 0.52%, which meet the accuracy requirements of the high precision binocular ranging.

  5. Bioinspired Gold Nanorod Functionalization Strategies for MUC1-Targeted Imaging and Photothermal Therapy

    Science.gov (United States)

    Zelasko-Leon, Daria Cecylia

    The majority of cancers diagnosed in 2016 are epithelial in origin, constituting 85% of all new cases and predicted to account for 78% of all cancer deaths this year. Given these statistics, improving patient outcomes by providing personalized, multimodal, and minimally invasive medical interventions is critically needed. Mucin 1 (MUC1), a transmembrane glycoprotein, extends over 100 nm from cell membranes and is a key marker promoting epithelial carcinogenesis. Due to its antenna-like manifestation, MUC1 is a unique yet underexplored candidate for targeted cancer therapy, with overexpression in >64% of epithelial cancers. To overcome the limitations of existing treatment strategies for epithelial cancer, this dissertation describes a novel platform for nanomedicine, highlighting bioinspired modifications of gold nanorod (AuNR) surfaces for diagnostic cancer imaging and photothermal therapy. An ongoing challenge in the field of nanomedicine is the need for simple and effective strategies for simple surface modification of nanoparticles to facilitate targeting and enhance efficacy. Here, biofunctionalization of AuNRs was achieved with polydopamine (PD) and tannic acid (TA), polyphenolic compounds found in the marine mussel and throughout the plant kingdom that exhibit promiscuous interfacial binding properties. AuNR stabilization was achieved via PD or TA coatings followed by secondary modification with the serum protein, bovine serum albumin (BSA), or glycoprotein-mimetic polymers. The resultant constructs demonstrated good biocompatibility, enabled diagnostic imaging, and facilitated MUC1-specific photothermal treatment of breast and oral cancer cells. The in vivo performance of BSA and PD modified AuNRs was evaluated in two orthotopic animal models of breast cancer. Clinically relevant hyperthermia and high response rates with MUC1-targeted formulations were found, with significant enhancement of progression-free survival and several complete tumor regressions

  6. Targeting Signaling Pathways in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Johannes Haybaeck

    2013-05-01

    Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are relevant for ovarian tumorigenesis. The understanding of these molecular pathways is essential for the development of novel therapeutic strategies. Purpose: We want to give an overview on the molecular genetic changes of the histopathological types of OC and their role as putative therapeutic targets. In Depth Review of Existing Data: In 2012, the vascular endothelial growth factor (VEGF inhibitor, bevacizumab, was approved for OC treatment. Bevacizumab has shown promising results as single agent and in combination with conventional chemotherapy, but its target is not distinctive when analyzed before treatment. At present, mammalian target of rapamycin (mTOR inhibitors, poly-ADP-ribose polymerase (PARP inhibitors and components of the EGFR pathway are in the focus of clinical research. Interestingly, some phytochemical substances show good synergistic effects when used in combination with chemotherapy. Conclusion: Ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative options to bevacizumab available for OC patients. Novel targets which can be assessed before therapy to predict efficacy are needed. The assessment of therapeutic targets is continuously improved by molecular pathological analyses on tumor tissue. A careful selection of patients for personalized treatment will help to reduce putative side effects and toxicity.

  7. Targeting the Checkpoint to Kill Cancer Cells

    Czech Academy of Sciences Publication Activity Database

    Benada, Jan; Macůrek, Libor

    2015-01-01

    Roč. 6, č. 3 (2015), s. 1912-1937 ISSN 2218-273X R&D Projects: GA ČR(CZ) GA14-34264S Institutional support: RVO:68378050 Keywords : checkpoint * DNA damage response * cancer Subject RIV: EB - Genetics ; Molecular Biology

  8. Mitochondria as targets for cancer therapy

    Czech Academy of Sciences Publication Activity Database

    Ralph, S.J.; Neužil, Jiří

    2009-01-01

    Roč. 53, č. 1 (2009), s. 9-28 ISSN 1613-4125 Institutional research plan: CEZ:AV0Z50520701 Keywords : Apoptosis * mitocans * cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.356, year: 2009

  9. Targeting Neuroendocrine Differentiation for Prostate Cancer Radiosensitization

    Science.gov (United States)

    2014-10-01

    doses when ACREB was expressed (Fig. 6A). Because clonogenic assay assesses the reproductive ability of cells after a single exposure, which is...29] Slovin SF. Neuroendocrine differentiation in prostate cancer: a sheep in wolf’s clothing? Nat Clin Pract Urol. 2006;3:138-144. [30] Lilleby W

  10. Targeting senescence cells in pancreatic cancer | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Cellular senescence is a programmed response to oncogenic (tumour-causing) stress that aims to halt the expansion of cells with malignant potential. It does this by stopping the proliferation of pre-cancerous lesions and recruitment of the immune system for their elimination. If these processes fail, senescent cells create ...

  11. Inhalable magnetic nanoparticles for targeted hyperthermia in lung cancer therapy.

    Science.gov (United States)

    Sadhukha, Tanmoy; Wiedmann, Timothy S; Panyam, Jayanth

    2013-07-01

    Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Biodegradable polymers for targeted delivery of anti-cancer drugs.

    Science.gov (United States)

    Doppalapudi, Sindhu; Jain, Anjali; Domb, Abraham J; Khan, Wahid

    2016-06-01

    Biodegradable polymers have been used for more than three decades in cancer treatment and have received increased interest in recent years. A range of biodegradable polymeric drug delivery systems designed for localized and systemic administration of therapeutic agents as well as tumor-targeting macromolecules has entered into the clinical phase of development, indicating the significance of biodegradable polymers in cancer therapy. This review elaborates upon applications of biodegradable polymers in the delivery and targeting of anti-cancer agents. Design of various drug delivery systems based on biodegradable polymers has been described. Moreover, the indication of polymers in the targeted delivery of chemotherapeutic drugs via passive, active targeting, and localized drug delivery are also covered. Biodegradable polymer-based drug delivery systems have the potential to deliver the payload to the target and can enhance drug availability at desired sites. Systemic toxicity and serious side effects observed with conventional cancer therapeutics can be significantly reduced with targeted polymeric systems. Still, there are many challenges that need to be met with respect to the degradation kinetics of the system, diffusion of drug payload within solid tumors, targeting tumoral tissue and tumor heterogeneity.

  13. Mitosis as an anti-cancer target.

    Science.gov (United States)

    Janssen, A; Medema, R H

    2011-06-23

    Most of the current drugs used to treat cancer can be classified as anti-proliferative drugs. These drugs perturb the proliferative cycle of tumor cells at diverse stages of the cell cycle. Examples of such drugs are DNA-damaging agents and inhibitors of cyclin-dependent kinases that arrest cell cycle progression at different stages of interphase. Another class of anti-proliferative drugs is the so-called anti-mitotic drugs, which selectively perturb progression through mitosis. Mitosis is the shortest and final stage in the cell cycle and has evolved to accurately divide the duplicated genome over the two daughter cells. This review deals with the different strategies that are currently considered to perturb mitotic progression in the treatment of cancer.

  14. Potential targets for colorectal cancer prevention.

    Science.gov (United States)

    Temraz, Sally; Mukherji, Deborah; Shamseddine, Ali

    2013-08-22

    The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB), survivin and insulin-like growth factor-I (IGF-I). Clinical trials of COX-2 inhibitors have provided the "proof of principle" that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research.

  15. Potential Targets for Colorectal Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Ali Shamseddine

    2013-08-01

    Full Text Available The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2, nuclear factor kappa B (NF-κB, survivin and insulin-like growth factor-I (IGF-I. Clinical trials of COX-2 inhibitors have provided the “proof of principle” that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research.

  16. Synthetic SAR Image Generation using Sensor, Terrain and Target Models

    DEFF Research Database (Denmark)

    Kusk, Anders; Abulaitijiang, Adili; Dall, Jørgen

    2016-01-01

    A tool to generate synthetic SAR images of objects set on a clutter background is described. The purpose is to generate images for training Automatic Target Recognition and Identification algorithms. The tool employs a commercial electromagnetic simulation program to calculate radar cross sections...... of the object using a CAD-model. The raw measurements are input to a SAR system and terrain model, which models thermal noise, terrain clutter, and SAR focusing to produce synthetic SAR images. Examples of SAR images at 0.3m and 0.1m resolution, and a comparison with real SAR imagery from the MSTAR dataset...

  17. Targeting PCNA Phosphorylation in Breast Cancer

    Science.gov (United States)

    2013-04-01

    inhibitors at high concentrations . Detection of PCNA Phosphorylation upon Kinase Inhibitor Treatment in MDA-MB-468 Breast Cancer Cells A panel of...Bradford assay to determine protein concentration . Bradford Assay and Total Protein Levels amongst Kinase Treatments The Bradford assay to determine...washed with water (2 x), Sat. aq. NaHCO3 (1 x) and brine . After being dried over Na2SO4, the solvent was concentrated under vacuum and the residue was

  18. Targeting TMPRSS2-ERG in Prostate Cancer

    Science.gov (United States)

    2015-09-01

    in E . coli and purified using Ni-NTA agarose. Eluted protein was analyzed by SDS- PAGE and Coomassie Blue staining. Left lane shows molecular...5d. PROJECT NUMBER 5e. TASK NUMBER E -Mail: 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) 8...TMPRSS2. The TMPRSS2-ERG fusion results in ERG becoming aberrantly activated in prostate cells, which contributes to the development of cancer. However

  19. Targeting ESR1-Mutant Breast Cancer

    Science.gov (United States)

    2015-09-01

    we have developed models of mutant ER driven cancer in which to characterize gene expression. Specifically, tetracycline inducible MCF7 cells that...expression profiling. Figure 1: Degradation of WT and mutant ER with ARN810. MCF7 cells stably transfected with tet-inducible WT and mutant...mutant ER. MCF7 cells stably transfected with tet- inducible WT and mutant ER are treated for 24 hours with estradiol and gene expression profiling

  20. Identification of novel vascular targets in lung cancer.

    Science.gov (United States)

    Zhuang, X; Herbert, J M J; Lodhia, P; Bradford, J; Turner, A M; Newby, P M; Thickett, D; Naidu, U; Blakey, D; Barry, S; Cross, D A E; Bicknell, R

    2015-02-03

    Lung cancer remains the leading cause of cancer-related death, largely owing to the lack of effective treatments. A tumour vascular targeting strategy presents an attractive alternative; however, the molecular signature of the vasculature in lung cancer is poorly explored. This work aimed to identify novel tumour vascular targets in lung cancer. Enzymatic digestion of fresh tissue followed by endothelial capture with Ulex lectin-coated magnetic beads was used to isolate the endothelium from fresh tumour specimens of lung cancer patients. Endothelial isolates from the healthy and tumour lung tissue were subjected to whole human genome expression profiling using microarray technology. Bioinformatics analysis identified tumour endothelial expression of angiogenic factors, matrix metalloproteases and cell-surface transmembrane proteins. Predicted novel tumour vascular targets were verified by RNA-seq, quantitative real-time PCR analysis and immunohistochemistry. Further detailed expression profiling of STEAP1 on 82 lung cancer patients confirmed STEAP1 as a novel target in the tumour vasculature. Functional analysis of STEAP1 using siRNA silencing implicates a role in endothelial cell migration and tube formation. The identification of cell-surface tumour endothelial markers in lung is of interest in therapeutic antibody and vaccine development.

  1. Aptamer-based radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of epithelial tumors

    Energy Technology Data Exchange (ETDEWEB)

    Missailidis, Sotiris [The Open University, Milton Keynes (United Kingdom). Dept. of Chemistry and Analytical Sciences]. E-mail: s.missailidis@open.ac.uk; Perkins, Alan [University of Nottingham (United Kingdom). Dept. of Medical Physics; Santos-Filho, Sebastiao David; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria

    2008-12-15

    In the continuous search for earlier diagnosis and improved therapeutic modalities against cancer, based on our constantly increasing knowledge of cancer biology, aptamers hold the promise to expand on current antibody success, but overcoming some of the problems faced with antibodies as therapeutic or delivery agents in cancer. However, as the first aptamer reached the market as an inhibitor against angiogenesis for the treatment of macular degeneration, aptamers have found only limited applications or interest in oncology, and even less as radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of tumours. Yet, the chemistry for the labelling of aptamers and the options to alter their pharmacokinetic properties, to make them suitable for use as radiopharmaceuticals is now available and recent advances in their development can demonstrate that these molecules would make them ideal delivery vehicles for the development of targeted radiopharmaceuticals that could deliver their radiation load with accuracy to the tumour site, offering improved therapeutic properties and reduced side effects. (author)

  2. Aptamer-based radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of epithelial tumors

    International Nuclear Information System (INIS)

    Missailidis, Sotiris; Perkins, Alan; Santos-Filho, Sebastiao David; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario

    2008-01-01

    In the continuous search for earlier diagnosis and improved therapeutic modalities against cancer, based on our constantly increasing knowledge of cancer biology, aptamers hold the promise to expand on current antibody success, but overcoming some of the problems faced with antibodies as therapeutic or delivery agents in cancer. However, as the first aptamer reached the market as an inhibitor against angiogenesis for the treatment of macular degeneration, aptamers have found only limited applications or interest in oncology, and even less as radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of tumours. Yet, the chemistry for the labelling of aptamers and the options to alter their pharmacokinetic properties, to make them suitable for use as radiopharmaceuticals is now available and recent advances in their development can demonstrate that these molecules would make them ideal delivery vehicles for the development of targeted radiopharmaceuticals that could deliver their radiation load with accuracy to the tumour site, offering improved therapeutic properties and reduced side effects. (author)

  3. Chromatin-regulating proteins as targets for cancer therapy

    International Nuclear Information System (INIS)

    Oike, Takahiro; Ogiwara, Hideaki; Kohno, Takashi; Amornwichet, Napapat; Nakano, Takashi

    2014-01-01

    Chromatin-regulating proteins represent a large class of novel targets for cancer therapy. In the context of radiotherapy, acetylation and deacetylation of histones by histone acetyltransferases (HATs) and histone deacetylases (HDACs) play important roles in the repair of DNA double-strand breaks generated by ionizing irradiation, and are therefore attractive targets for radiosensitization. Small-molecule inhibitors of HATs (garcinol, anacardic acid and curcumin) and HDACs (vorinostat, sodium butyrate and valproic acid) have been shown to sensitize cancer cells to ionizing irradiation in preclinical models, and some of these molecules are being tested in clinical trials, either alone or in combination with radiotherapy. Meanwhile, recent large-scale genome analyses have identified frequent mutations in genes encoding chromatin-regulating proteins, especially in those encoding subunits of the SWI/SNF chromatin-remodeling complex, in various human cancers. These observations have driven researchers toward development of targeted therapies against cancers carrying these mutations. DOT1L inhibition in MLL-rearranged leukemia, EZH2 inhibition in EZH2-mutant or MLL-rearranged hematologic malignancies and SNF5-deficient tumors, BRD4 inhibition in various hematologic malignancies, and BRM inhibition in BRG1-deficient tumors have demonstrated promising anti-tumor effects in preclinical models, and these strategies are currently awaiting clinical application. Overall, the data collected so far suggest that targeting chromatin-regulating proteins is a promising strategy for tomorrow's cancer therapy, including radiotherapy and molecularly targeted chemotherapy. (author)

  4. Range-gated imaging for near-field target identification

    Energy Technology Data Exchange (ETDEWEB)

    Yates, G.J.; Gallegos, R.A.; McDonald, T.E. [and others

    1996-12-01

    The combination of two complementary technologies developed independently at Los Alamos National Laboratory (LANL) and Sandia National Laboratory (SNL) has demonstrated feasibility of target detection and image capture in a highly light-scattering, medium. The technique uses a compact SNL developed Photoconductive Semiconductor Switch/Laser Diode Array (PCSS/LDA) for short-range (distances of 8 to 10 m) large Field-Of-View (FOV) target illumination. Generation of a time-correlated echo signal is accomplished using a photodiode. The return image signal is recorded with a high-speed shuttered Micro-Channel-Plate Image Intensifier (MCPII), declined by LANL and manufactured by Philips Photonics. The MCPII is rated using a high-frequency impedance-matching microstrip design to produce 150 to 200 ps duration optical exposures. The ultra first shuttering producer depth resolution of a few inches along the optic axis between the MCPII and the target, producing enhanced target images effectively deconvolved from noise components from the scattering medium in the FOV. The images from the MCPII are recorded with an RS-170 Charge-Coupled-Device camera and a Big Sky, Beam Code, PC-based digitizer frame grabber and analysis package. Laser pulse data were obtained by the but jitter problems and spectral mismatches between diode spectral emission wavelength and MCPII photocathode spectral sensitivity prevented the capture of fast gating imaging with this demonstration system. Continued development of the system is underway.

  5. Polymer encapsulated upconversion nanoparticle/iron oxide nanocomposites for multimodal imaging and magnetic targeted drug delivery.

    Science.gov (United States)

    Xu, Huan; Cheng, Liang; Wang, Chao; Ma, Xinxing; Li, Yonggang; Liu, Zhuang

    2011-12-01

    Multimodal imaging and imaging-guided therapies have become a new trend in the current development of cancer theranostics. In this work, we encapsulate hydrophobic upconversion nanoparticles (UCNPs) together with iron oxide nanoparticles (IONPs) by using an amphiphilic block copolymer, poly (styrene-block-allyl alcohol) (PS(16)-b-PAA(10)), via a microemulsion method, obtaining an UC-IO@Polymer multi-functional nanocomposite system. Fluorescent dye and anti-cancer drug molecules can be further loaded inside the UC-IO@Polymer nanocomposite for additional functionalities. Utilizing the Squaraine (SQ) dye loaded nanocomposite (UC-IO@Polymer-SQ), triple-modal upconversion luminescence (UCL)/down-conversion fluorescence (FL)/magnetic resonance (MR) imaging is demonstrated in vitro and in vivo, and also applied for in vivo cancer cell tracking in mice. On the other hand, a chemotherapy drug, doxorubicin, is also loaded into the nanocomposite, forming an UC-IO@Polymer-DOX complex, which enables novel imaging-guided and magnetic targeted drug delivery. Our work provides a method to fabricate a nanocomposite system with highly integrated functionalities for multimodal biomedical imaging and cancer therapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Trastuzumab Sensitizes Ovarian Cancer Cells to EGFR-targeted Therapeutics

    Directory of Open Access Journals (Sweden)

    Wilken Jason A

    2010-03-01

    Full Text Available Abstract Background Early studies have demonstrated comparable levels of HER2/ErbB2 expression in both breast and ovarian cancer. Trastuzumab (Herceptin, a therapeutic monoclonal antibody directed against HER2, is FDA-approved for the treatment of both early and late stage breast cancer. However, clinical studies of trastuzumab in epithelial ovarian cancer (EOC patients have not met the same level of success. Surprisingly, however, no reports have examined either the basis for primary trastuzumab resistance in ovarian cancer or potential ways of salvaging trastuzumab as a potential ovarian cancer therapeutic. Methods An in vitro model of primary trastuzumab-resistant ovarian cancer was created by long-term culture of HER2-positive ovarian carcinoma-derived cell lines with trastuzumab. Trastuzumab treated vs. untreated parental cells were compared for HER receptor expression, trastuzumab sensitivity, and sensitivity to other HER-targeted therapeutics. Results In contrast to widely held assumptions, here we show that ovarian cancer cells that are not growth inhibited by trastuzumab are still responsive to trastuzumab. Specifically, we show that responsiveness to alternative HER-targeted inhibitors, such as gefitinib and cetuximab, is dramatically potentiated by long-term trastuzumab treatment of ovarian cancer cells. HER2-positive ovarian carcinoma-derived cells are, therefore, not "unresponsive" to trastuzumab as previously assumed, even when they not growth inhibited by this drug. Conclusions Given the recent success of EGFR-targeted therapeutics for the treatment of other solid tumors, and the well-established safety profile of trastuzumab, results presented here provide a rationale for re-evaluation of trastuzumab as an experimental ovarian cancer therapeutic, either in concert with, or perhaps as a "primer" for EGFR-targeted therapeutics.

  7. Fusion Imaging in the Diagnosis of Cancer

    International Nuclear Information System (INIS)

    Maldonado, A.; Gonzalez Alenda, J.

    2007-01-01

    Early diagnosis is one of the most important aids in the fight against cancer. Of the tests available in Medicine, anatomic imaging techniques such as Computed Tomography (CT)and Magnetic Resonance Imaging (MRI) have been the ones used for many years. the emergence of Positron Emission Tomography (PET) more than a decade ago was a major breakthrough in the early diagnosis of malignant lesions, as it was based on tumor metabolism and not on anatomy. The merger of both techniques into one thanks to PET-CT cameras has made this technology the most important tool in the management of cancer patients. (Author)

  8. Mitochondrially targeted anti-cancer agents

    Czech Academy of Sciences Publication Activity Database

    Biasutto, L.; Dong, L.A.; Zoratti, M.; Neužil, Jiří

    2010-01-01

    Roč. 10, č. 6 (2010), s. 670-681 ISSN 1567-7249 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitochondrial targeting * pro-oxidant effect * reactive oxygen species Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.238, year: 2010

  9. Optical Coherence Tomography in Cancer Imaging

    Science.gov (United States)

    Nam, Ahhyun Stephanie; Vakoc, Benjamin; Blauvelt, David; Chico-Calero, Isabel

    Investigations into the biology of cancer and novel cancer therapies rely on preclinical mouse models and traditional histological endpoints. Drawbacks of this approach include a limit in the number of time points for evaluation and an increased number of animals per study. This has motivated the use of intravital microscopy, which can provide longitudinal imaging of critical tumor parameters. Here, the capabilities of OCT as an intravital microscopy of the tumor microenvironment are summarized, and the state of OCT adoption into cancer research is summarized.

  10. Nanotechnology for sensing, imaging, and treating cancer.

    Science.gov (United States)

    Panchapakesan, Balaji; Wickstrom, Eric

    2007-04-01

    Nanotechnology encompasses the creation and use of materials, devices, and systems at the level of atoms, molecules, and supramolecular structures. Nanotechnology for cancer consists of three main areas: (1) nanodetectors for sensing proteins and cancer cells, (2) nanoparticle or nanovector formulations for high-contrast imaging, and (3) nanotechnology-based drug delivery and therapeutic formulations. Although there are tremendous challenges facing nanotechnologists, nanotechnology, if properly integrated with established cancer research, can make laboratory-to-clinic transfer of technology successful, which can result in breakthrough potential for patient care.

  11. Synthetic Genetic Targeting of Genome Instability in Cancer

    International Nuclear Information System (INIS)

    Sajesh, Babu V.; Guppy, Brent J.; McManus, Kirk J.

    2013-01-01

    Cancer is a leading cause of death throughout the World. A limitation of many current chemotherapeutic approaches is that their cytotoxic effects are not restricted to cancer cells, and adverse side effects can occur within normal tissues. Consequently, novel strategies are urgently needed to better target cancer cells. As we approach the era of personalized medicine, targeting the specific molecular defect(s) within a given patient’s tumor will become a more effective treatment strategy than traditional approaches that often target a given cancer type or sub-type. Synthetic genetic interactions are now being examined for their therapeutic potential and are designed to target the specific genetic and epigenetic phenomena associated with tumor formation, and thus are predicted to be highly selective. In general, two complementary approaches have been employed, including synthetic lethality and synthetic dosage lethality, to target aberrant expression and/or function associated with tumor suppressor genes and oncogenes, respectively. Here we discuss the concepts of synthetic lethality and synthetic dosage lethality, and explain three general experimental approaches designed to identify novel genetic interactors. We present examples and discuss the merits and caveats of each approach. Finally, we provide insight into the subsequent pre-clinical work required to validate novel candidate drug targets

  12. X-ray image intensifier camera tubes and semiconductor targets

    International Nuclear Information System (INIS)

    1979-01-01

    A semiconductor target for use in an image intensifier camera tube and a camera using the target are described. The semiconductor wafer for converting an electron image onto electrical signal consists mainly of a collector region, preferably n-type silicon. It has one side for receiving the electron image and an opposite side for storing charge carriers generated in the collector region by high energy electrons forming a charge image. The first side comprises a highly doped surface layer covered with a metal buffer layer permeable to the incident electrons and thick enough to dissipate some of the incident electron energy thereby improving the signal-to-noise ratio. This layer comprises beryllium on niobium on the highly doped silicon surface zone. Low energy Kα X-ray radiation is generated in the first layer, the radiation generated in the second layer (mainly Lα radiation) is strongly absorbed in the silicon layer. A camera tube using such a target with a photocathode for converting an X-ray image into an electron image, means to project this image onto the first side of the semiconductor wafer and means to read out the charge pattern on the second side are also described. (U.K.)

  13. Targeted nanotechnologies for cancer intervention: a patent review (2010-2016).

    Science.gov (United States)

    Pradeep, Priyamvada; Kumar, Pradeep; Choonara, Yahya E; Pillay, Viness

    2017-09-01

    In recent years, several active targeting nanostrategies have been patented for application in cancer theranostics. The versatility of nanostructures in terms of composition, manufacturability, functionalization, and matrix formation make them ideal for carrying large dose of bioactive contents, high density of targeting ligands on their surface, efficient delivery to the site of interest, and capable of forming multicomponent platforms. Areas covered: The patents were classified into polymeric and non-polymeric nanostructures and their applicability in addressing the targeting paradigm related to cancer intervention was explored. Specialized platforms such as nanoparticles, nanomicelles, nanocomposites, nanotubes, quantum dots, metal/silica particles, and dendrimers were cited as targeted nanostructures along with ligands such as antibody fragments, synthetic peptides, aptamers, small molecules, and folates. Here, we focused on patented targeted nanotechnological advances in recent years (2010-2016). Expert opinion: The formulation and performance prerequisites, available nanomaterial options, fabrication feasibility, and challenges and issues related with regulatory approval and patenting of cancer targeted nanocarriers are reviewed. Future research in this area should focus on clinically relevant bioactive combinations, better metastasis control, integration of imaging and theranostic techniques, predictive animal/pre-clinical models, maximal utilisation of extra- and intracellular tumor microenvironment for drug delivery, and exploring the metabolomic-, proteomic-, and genomic-based personalization of cancer nanomedicine.

  14. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    Directory of Open Access Journals (Sweden)

    Vermeulen Jeroen F

    2012-06-01

    Full Text Available Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Methods Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. Results The combination of highly tumor-specific markers glucose transporter 1 (GLUT1, epidermal growth factor receptor (EGFR, insulin-like growth factor-1 receptor (IGF1-R, human epidermal growth factor receptor 2 (HER2, hepatocyte growth factor receptor (MET, and carbonic anhydrase 9 (CAIX 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6 resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. Conclusions In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  15. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    International Nuclear Information System (INIS)

    Vermeulen, Jeroen F; Brussel, Aram SA van; Groep, Petra van der; Morsink, Folkert HM; Bult, Peter; Wall, Elsken van der; Diest, Paul J van

    2012-01-01

    Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate

  16. Mitosis as an anti-cancer drug target.

    Science.gov (United States)

    Salmela, Anna-Leena; Kallio, Marko J

    2013-10-01

    Suppression of cell proliferation by targeting mitosis is one potential cancer intervention. A number of existing chemotherapy drugs disrupt mitosis by targeting microtubule dynamics. While efficacious, these drugs have limitations, i.e. neuropathy, unpredictability and development of resistance. In order to overcome these issues, a great deal of effort has been spent exploring novel mitotic targets including Polo-like kinase 1, Aurora kinases, Mps1, Cenp-E and KSP/Eg5. Here we summarize the latest developments in the discovery and clinical evaluation of new mitotic drug targets.

  17. Cancer stem cells, the ultimate targets in cancer therapy

    OpenAIRE

    Shabbir A; Esfandyari T; Farassati F

    2018-01-01

    Ahmed Shabbir,1 Tuba Esfandyari,2 Faris Farassati1,3,4 1Midwest Biomedical Research Foundation, Kansas City Veterans Affairs Medical Center, 2Department of Medicine, School of Medicine, The University of Kansas, 3Saint Luke’s Cancer Institute, 4Saint Luke’s Marion Bloch Neuroscience Institute, Saint Luke’s Health System, Kansas City, MO, USAThe concept of cancer stem cells (CSCs) is currently of significant interest due to its important implications in our under...

  18. Smac Mimetics to Therapeutically Target IAP Proteins in Cancer.

    Science.gov (United States)

    Fulda, S

    2017-01-01

    Inhibitor of Apoptosis (IAP) proteins are overexpressed in a variety of human cancers. Therefore, they are considered as promising targets for the design of therapeutic strategies. Smac mimetics mimic the endogenous mitochondrial protein Smac that antagonizes IAP proteins upon its release into the cytosol. Multiple preclinical studies have documented the ability of Smac mimetics to either directly induce cell death of cancer cells or to prime them to agents that trigger cell death. At present, several Smac mimetics are being evaluated in early clinical trials. The current review provides an overview on the potential of Smac mimetics as cancer therapeutics to target IAP proteins for cancer therapy. © 2017 Elsevier Inc. All rights reserved.

  19. Therapeutic Implications of Targeting Energy Metabolism in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Meena K. Sakharkar

    2013-01-01

    Full Text Available PPARs are ligand activated transcription factors. PPARγ agonists have been reported as a new and potentially efficacious treatment of inflammation, diabetes, obesity, cancer, AD, and schizophrenia. Since cancer cells show dysregulation of glycolysis they are potentially manageable through changes in metabolic environment. Interestingly, several of the genes involved in maintaining the metabolic environment and the central energy generation pathway are regulated or predicted to be regulated by PPARγ. The use of synthetic PPARγ ligands as drugs and their recent withdrawal/restricted usage highlight the lack of understanding of the molecular basis of these drugs, their off-target effects, and their network. These data further underscores the complexity of nuclear receptor signalling mechanisms. This paper will discuss the function and role of PPARγ in energy metabolism and cancer biology in general and its emergence as a promising therapeutic target in breast cancer.

  20. Anthocyanins: targeting of signaling networks in cancer cells.

    Science.gov (United States)

    Sehitoglu, Muserref Hilal; Farooqi, Ammad Ahmad; Qureshi, Muhammad Zahid; Butt, Ghazala; Aras, Aliye

    2014-01-01

    It is becoming progressively more understandable that phytochemicals derived from edible plants have shown potential in modelling their interactions with their target proteins. Rapidly accumulating in-vitro and in- vivo evidence indicates that anthocyanins have anticancer activity in rodent models of cancer. More intriguingly, evaluation of bilberry anthocyanins as chemopreventive agents in twenty-five colorectal cancer patients has opened new window of opportunity in translating the findings from laboratory to clinic. Confluence of information suggests that anthocyanins treated cancer cells reveal up-regulation of tumor suppressor genes. There is a successive increase in the research-work in nutrigenomics and evidence has started to shed light on intracellular-signaling cascades as common molecular targets for anthocyanins. In this review we bring to limelight how anthocyanins induced apoptosis in cancer cells via activation of extrinsic and intrinsic pathways.

  1. Targeting Cancer Stem Cells and Their Niche: Current Therapeutic Implications and Challenges in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Jiangang Zhao

    2017-01-01

    Full Text Available Cancer stem cells (CSCs have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting. We propose that immunotherapy targeting pancreatic CSCs, in combination with targeting the niche components, may provide a novel treatment strategy to eradicate pancreatic CSCs and hence improve outcomes in pancreatic cancer.

  2. Targeting cancer cell mitochondria as a therapeutic approach: recent updates.

    Science.gov (United States)

    Cui, Qingbin; Wen, Shijun; Huang, Peng

    2017-06-01

    Mitochondria play a key role in ATP generation, redox homeostasis and regulation of apoptosis. Due to the essential role of mitochondria in metabolism and cell survival, targeting mitochondria in cancer cells is considered as an attractive therapeutic strategy. However, metabolic flexibility in cancer cells may enable the upregulation of compensatory pathways, such as glycolysis to support cancer cell survival when mitochondrial metabolism is inhibited. Thus, compounds capable of both targeting mitochondria and inhibiting glycolysis may be particularly useful to overcome such drug-resistant mechanism. This review provides an update on recent development in the field of targeting mitochondria and novel compounds that impact mitochondria, glycolysis or both. Key challenges in this research area and potential solutions are also discussed.

  3. Photodynamic therapy and imaging based on tumor-targeted nanoprobe, polymer-conjugated zinc protoporphyrin

    Science.gov (United States)

    Fang, Jun; Liao, Long; Yin, Hongzhuan; Nakamura, Hideaki; Subr, Vladimir; Ulbrich, Karel; Maeda, Hiroshi

    2015-01-01

    Aim: To evaluate the potential of tumor-targeted nanoprobe, N-(2-hydroxypropyl)methacrylamide copolymer-conjugated zinc protoporphyrin (PZP) for photodynamic therapy (PDT) and tumor imaging. Materials & Methods: Different tumor models including carcinogen-induced cancer were used, PZP was intravenously injected followed by irradiation with xenon or blue fluorescent light on tumor. Results: One PZP 20 mg/kg (ZnPP equivalent) dose with two or three treatments of light at an intensity of ≥20 J/cm2 caused necrosis and disappearance of most tumors (>70%) in different tumor models. We also confirmed PZP-based tumor imaging in carcinogen-induced breast tumor and colon cancer models. Conclusion: These findings support the potential application of PZP as a tumor-selective nanoprobe for PDT as well as tumor imaging, by virtue of the enhanced permeability and retention effect. PMID:28031879

  4. Targeting Ovarian Cancer with Porphysome Nanotechnology

    Science.gov (United States)

    2015-10-01

    64- Copper of quality suitable for human administration, and the preliminary pharmacology and toxicology profile of radio-pharmaceutical Porphysome in...preclinical models. Radiation dosimetry and acute toxicology remain outstanding tasks before the Porphysome may proceed towards CTA submission with...barrier to translation is the dose [4]: the dose required to obtain the desired effect (effective dose), the dose at which off-target toxicity is

  5. Targeted Radiation Therapy for Cancer Initiative

    Science.gov (United States)

    2017-11-01

    CONTRACTING ORGANIZATION: The Geneva Foundation , Tacoma, WA 98402 REPORT DATE: November 2017 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical...ADDRESS. 1. REPORT DATE November 2017 2. REPORT TYPE Final 3. DATES COVERED 08/04/2008 - 08/03/2017 4. TITLE AND SUBTITLE Targeted Radiation Therapy...REPORT NUMBER The Geneva Foundation 917 Pacific Ave, Suite 600 Tacoma, WA 98402 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR

  6. Targeting Ovarian Cancer with Porphysome Nanotechnology

    Science.gov (United States)

    2014-10-01

    Institute of Biomaterials and Biomedical Engineering University of Toronto 101 College Street, Toronto, Ontario M5G 1L7, Canada L. Cui, Prof. G. Zheng...necrosis pathway. [ 3 ] Whereas PDT generates singlet oxygen as the predominant cytotoxic agent to damage the region restricted to...porphyrin con- centration of 5 × 10 −6 M . Upon PDT laser treatment (671 nm, 10 J cm − 2 ), non-targeting porphysome induced minor photo- cytotoxicity

  7. A Laser-Activated Biocompatible Theranostic Nanoagent for Targeted Multimodal Imaging and Photothermal Therapy.

    Science.gov (United States)

    Deng, Liming; Cai, Xiaojun; Sheng, Danli; Yang, Yang; Strohm, Eric M; Wang, Zhigang; Ran, Haitao; Wang, Dong; Zheng, Yuanyi; Li, Pan; Shang, Tingting; Ling, Yi; Wang, Fengjuan; Sun, Yang

    2017-01-01

    Multifunctional nanoparticles have been reported for cancer detection and treatment currently. However, the accurate diagnosis and efficient treatment for tumors are still not satisfied. Here we report on the development of targeted phase change multimodal polymeric nanoparticles for the imaging and treatment of HER2-positive breast cancer. We evaluated the multimodal imaging capabilities of the prepared nanoparticles in vitro using agar-based phantoms. The targeting performance and cytotoxicity of the nanoparticles were examined in cell culture using SKBR3 (over-expressing HER2) and MDA-MB-231 (HER2 negative) cells. We then tested the magnetic resonance (MR)/ photoacoustic (PA)/ ultrasound (US)/ near-infrared fluorescence (NIRF) multimodal imaging properties and photothermal effect of the nanoparticles in vivo using a SKBR3 breast xenograft model in nude mice. Tissue histopathology and immunofluorescence were also conducted. Both in vitro and in vivo systematical studies validated that the hybrid nanoparticles can be used as a superb MR/US/PA/NIRF contrast agent to simultaneously diagnose and guide tumor photothermal therapy (PTT). When irradiated by a near infrared laser, the liquid PFP vaporizes to a gas, rapidly expelling the contents and damaging surrounding tissues. The resulting micro-sized bubbles provide treatment validation through ultrasound imaging. Localization of DIR and SPIO in the tumor region facilitate photothermal therapy for targeted tumor destruction. The mice treated with HER2 targeted nanoparticles had a nearly complete response to treatment, while the controls showed continued tumor growth. This novel theranostic agent may provide better diagnostic imaging and therapeutic potential than current methods for treating HER2-positive breast cancer.

  8. A multistage target tracker in IR image sequences

    Science.gov (United States)

    Huang, Qiao; Yang, Jie

    2014-07-01

    In this paper, we propose a robust approach for tracking target in forward looking infrared imagery taken from an airborne moving platform. The tracker is proposed in a two stage algorithm with a coarse to fine manner. First, we introduce a coarse but quick algorithm to roughly locate the target, which based on a model matching procedure by computing the SIFT vector of the target. The raw position and the size of the target are then used to initialize the multistage tracking algorithm. Second, the target's position is refined through a dedicated localization algorithm, which based on a HOG feature tracking procedure to overcome the rapid size and angel changes of the dim target in the IR image sequence. Finally, the target's model can automatically been updated and utilized in the first stage. As confirmed by experimental results on a variety of IR image sequences, the proposed approach efficiently and robustly tracks target under challenging environmental conditions. Moreover, the speed of the multistage algorithm is also convincing in the tested IR imagery.

  9. Clinical target volume for rectal cancer. Preoperative radiotherapy

    International Nuclear Information System (INIS)

    Lorchel, F.; Bossel, J.F.; Baron, M.H.; Goubard, O.; Bartholomot, B.; Mantion, G.; Pelissier, E.P.; Maingon, P.

    2001-01-01

    The total meso-rectal excision allows the marked increase of the local control rate in rectal cancer. Therefore, the meso-rectal space is the usual field for the spread of rectal cancer cells. It could therefore be considered as the clinical target volume in the preoperative plan by the radiation oncologist. We propose to identify the mesorectum on anatomical structures of a treatment-position CT scan. (authors)

  10. Aptamer-conjugated nanobubbles for targeted ultrasound molecular imaging.

    Science.gov (United States)

    Wang, Chung-Hsin; Huang, Yu-Fen; Yeh, Chih-Kuang

    2011-06-07

    Targeted ultrasound contrast agents can be prepared by some specific bioconjugation techniques. The biotin-avidin complex is an extremely useful noncovalent binding system, but the system might induce immunogenic side effects in human bodies. Previous proposed covalently conjugated systems suffered from low conjugation efficiency and complex procedures. In this study, we propose a covalently conjugated nanobubble coupling with nucleic acid ligands, aptamers, for providing a higher specific affinity for ultrasound targeting studies. The sgc8c aptamer was linked with nanobubbles through thiol-maleimide coupling chemistry for specific targeting to CCRF-CEM cells. Further improvements to reduce the required time and avoid the degradation of nanobubbles during conjugation procedures were also made. Several investigations were used to discuss the performance and consistency of the prepared nanobubbles, such as size distribution, conjugation efficiency analysis, and flow cytometry assay. Further, we applied our conjugated nanobubbles to ex vivo ultrasound targeted imaging and compared the resulting images with optical images. The results indicated the availability of aptamer-conjugated nanobubbles in targeted ultrasound imaging and the practicability of using a highly sensitive ultrasound system in noninvasive biological research.

  11. Evaluation of image metrics for target discrimination using psychophysical experiments

    Science.gov (United States)

    Copeland, Anthony C.; Trivedi, Mohan M.; McManamey, James R.

    1996-06-01

    Image clutter affects the perceptual ability of any system for object detection. A procedure for conducting psychophysical experiments has been developed to test computational models for the perceptual similarity or difference of texture patterns, which contributes to image clutter. This experimental procedure is based on Thurstone's law of comparative judgment, which is used along with the method of paired comparisons to assign relative psychological scale values to image stimuli. To facilitate consistency in the presentation of stimuli and collection of data, an X-windows testing environment has been developed called the X-based perceptual experiment testbed. Using this experimental procedure, a pilot study was conducted in which the image stimuli consisted of targets and backgrounds with texture patterns of uncorrelated Gaussian noise. With such patterns, only first-order image statistics are of significance. The psychological scale values relating the level of `target distinctness' in each of the image stimuli were compared to several first-order image metrics. Correlation coefficients as high as 0.9881 were found between the scale values and the image metrics.

  12. New strategy of cancer therapy by targeting the hypoxic circumstances

    International Nuclear Information System (INIS)

    Yasui, Hironobu; Yamamori, Tohru; Meike, Shunsuke; Eitaki, Masato; Kuwabara, Mikinori; Inanami, Osamu; Iizuka, Daisuke

    2010-01-01

    Described are studies on the sensitization of tumor cells in hypoxic circumstances (known as radio-resistant cells) by authors' recent molecular targeting to adaptive response as well as by the usual agents like nitro-imidazole compounds, and on the intermittent hypoxia, a new topic in this field. The hypoxia-inducible factor-1 (HIF-1) is a transcriptional factor and has been known to activate its many downstream genes to cause adoptive response of hypoxic cells. Authors have studied the anti-tumor and radiation sensitizing effects of ethynyl-cytidine (EC) which is found to suppress RNA synthesis through cytidine kinase (CK) inhibition, and the compound is of specificity to tumor cells as they have 5-10 times higher CK activity than normal cells. Authors have also found that EC is of the sensitizing efficacy to normoxic and hypoxic cells by enhancing the radiation-induced apoptosis essentially through inhibition of HIF-1 expression. Intermittent hypoxia in the tumor which has characteristic abnormal vascular morphology and function, occurs by the transient reduction of blood flow and occlusion of vessels in the tissue within minute to hour time cycles. Little is known about the regional hypoxic region and its distribution in the tumor due to difficulty of their detection and quantification. For this, authors have measured the temporal changes of oxygen levels in the mouse tumor with triaryl methyl radical, an oxygen-sensitive contrast compound continuously injected, by microwave-pulsed electron spin resonance imaging (EPRI). By superimposing the EPRI and T2-weighted MRI, the oxymetric imaging is possible in the tumor, which reveals the difference of oxygen level variation depending on the cell type and tissue size. Findings in the field are expected to give important information for more effective cancer therapy and its prognostic prediction in future. (T.T.)

  13. Screening Technologies for Target Identification in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Michl, Patrick, E-mail: michlp@med.uni-marburg.de; Ripka, Stefanie; Gress, Thomas; Buchholz, Malte [Department of Gastroenterology and Endocrinology, University Hospital, Philipps-University Marburg, Baldinger Strasse, D-35043 Marburg (Germany)

    2010-12-29

    Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments.

  14. Advances of Molecular Subtype and Targeted Therapy of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Lan SHAO

    2012-09-01

    Full Text Available The discovery of multiple molecular mechanisms underlying the development, progression, and prognosis of lung cancer, has created new opportunities for targeted therapy. Each subtype is associated with molecular tests that define the subtype and drugs that may have potential therapeutic effect on lung cancer. In 2004, mutations in the epidermal growth factor receptor (epidermal growth factor receptor, EGFR gene were discovered in non-small cell lung cancers (NSCLC, especially in adenocarcinomas. And they are strongly associated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs. Moreover, in 2007 the existence of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK fusion gene was discovered in NSCLC, and the same as EGFR-TKIs, ALK inhibitors are being found to be highly effective in lung cancers. At present, multiple molecular subtype of lung cancer and relevant targeted drugs are undering study. Here, we review the remarkable progress in molecular subtype of lung cancer and the related targeted therapy.

  15. Screening Technologies for Target Identification in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Michl, Patrick; Ripka, Stefanie; Gress, Thomas; Buchholz, Malte

    2010-01-01

    Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments

  16. [Targeted radionuclide therapy for castration-resistant prostate cancer].

    Science.gov (United States)

    Nakamura, Katsumasa; Ohga, Saiji; Sasaki, Tomonari; Baba, Shingo; Honda, Hiroshi

    2014-12-01

    Although patients with castration-resistant prostate cancer frequently have metastases to the bone, they have a relatively favorable prognosis. Therefore, it is important to keep or improve the level of patient's quality of life. The use of strontium-89 for the management of the pain from bone metastasis was approved in 2007 in Japan. A new bone-targeting radiopharmaceuticals using radium-223 is also promising, because a randomized trial showed an overall survival advantage of radium-223 in prostate patients with bone metastases. In this review, we summarize the role of targeted radionuclide therapy for castration-resistant prostate cancer, focusing on strontium-89 and radium-223.

  17. Optical imaging of cancer and cell death

    NARCIS (Netherlands)

    Xie, Bangwen

    2013-01-01

    The aim of the work included in this PhD thesis was to explore the diverse application possibility of using NIR fluorescent probes with specific properties to visualize and characterize cancer and cell death. In this thesis, we mainly focus on optical imaging and its application, both at microscopic

  18. Ultrasound Imaging Methods for Breast Cancer Detection

    NARCIS (Netherlands)

    Ozmen, N.

    2014-01-01

    The main focus of this thesis is on modeling acoustic wavefield propagation and implementing imaging algorithms for breast cancer detection using ultrasound. As a starting point, we use an integral equation formulation, which can be used to solve both the forward and inverse problems. This thesis

  19. Metastatic gastric cancer – focus on targeted therapies

    Directory of Open Access Journals (Sweden)

    Meza-Junco J

    2012-06-01

    Full Text Available Judith Meza-Junco, Michael B SawyerDepartment of Oncology, Cross Cancer Institute, Edmonton, Alberta, CanadaAbstract: Gastric cancer (GC is currently the second leading cause of cancer death worldwide; unfortunately, most patients will present with locally advanced or metastatic disease. Despite recent progress in diagnosis, surgery, chemotherapy, and radiotherapy, prognosis remains poor. A better understanding of GC biology and signaling pathways is expected to improve GC therapy, and the integration of targeted therapies has recently become possible and appears to be promising. This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib. Additionally, drugs that target angiogenesis pathways are also under investigation, particulary bevacizumab, ramucirumab, sorafenib, sunitinib, and cediranib. Other targeted agents in preclinical or early clinical development include mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors, anti-insulin-like growth factor, anti-heat shock proteins, and small molecules targeting Hedgehog signaling.Keywords: gastric cancer, targeted therapy, antiangiogenesis drugs, anti-EGFR drugs

  20. Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

    Science.gov (United States)

    Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S.; Zhang, Yan-Bing; Zi, Xiaolin

    2014-01-01

    There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcones from both natural products and synthesis have been identified in a variety of screening assays for modulating important pathways or molecular targets in cancers. These pathways and targets that are affected by chalcones include MDM2/p53, tubulin, proteasome, NF-kappa B, TRIAL/death receptors and mitochondria mediated apoptotic pathways, cell cycle, STAT3, AP-1, NRF2, AR, ER, PPAR-γ and β-catenin/Wnt. Compared to current cancer targeted therapeutic drugs, chalcones have the advantages of being inexpensive, easily available and less toxic; the ease of synthesis of chalcones from substituted benzaldehydes and acetophenones also makes them an attractive drug scaffold. Therefore, this review is focused on molecular targets of chalcones and their potential implications in cancer prevention and therapy. PMID:24467530

  1. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2017-12-01

    AWARD NUMBER: W81XWH-14-1-0553 TITLE: Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer PRINCIPAL INVESTIGATOR: Martin Gleave...Siah2 as Novel Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0553 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Martin Gleave 5d...goal of this project was to develop a novel means to inhibit prostate cancer development and progression. The development of Siah1/2 inhibitors to the

  2. BMI-1, a promising therapeutic target for human cancer

    Science.gov (United States)

    WANG, MIN-CONG; LI, CHUN-LI; CUI, JIE; JIAO, MIN; WU, TAO; JING, LI; NAN, KE-JUN

    2015-01-01

    BMI-1 oncogene is a member of the polycomb-group gene family and a transcriptional repressor. Overexpression of BMI-1 has been identified in various human cancer tissues and is known to be involved in cancer cell proliferation, cell invasion, distant metastasis, chemosensitivity and patient survival. Accumulating evidence has revealed that BMI-1 is also involved in the regulation of self-renewal, differentiation and tumor initiation of cancer stem cells (CSCs). However, the molecular mechanisms underlying these biological processes remain unclear. The present review summarized the function of BMI-1 in different human cancer types and CSCs, and discussed the signaling pathways in which BMI-1 is potentially involved. In conclusion, BMI-1 may represent a promising target for the prevention and therapy of various cancer types. PMID:26622537

  3. Therapeutic targeting of cancers with loss of PTEN function

    Science.gov (United States)

    Dillon, Lloye M.; Miller, Todd W.

    2015-01-01

    Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is one of the most frequently disrupted tumor suppressors in cancer. The lipid phosphatase activity of PTEN antagonizes the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway to repress tumor cell growth and survival. In the nucleus, PTEN promotes chromosome stability and DNA repair. Consequently, loss of PTEN function increases genomic instability. PTEN deficiency is caused by inherited germline mutations, somatic mutations, epigenetic and transcriptional silencing, post-translational modifications, and protein-protein interactions. Given the high frequency of PTEN deficiency across cancer subtypes, therapeutic approaches that exploit PTEN loss-of-function could provide effective treatment strategies. Herein, we discuss therapeutic strategies aimed at cancers with loss of PTEN function, and the challenges involved in treating patients afflicted with such cancers. We review preclinical and clinical findings, and highlight novel strategies under development to target PTEN-deficient cancers. PMID:24387334

  4. Targeting the extracellular matrix to disrupt cancer progression

    Directory of Open Access Journals (Sweden)

    Freja Albjerg Venning

    2015-10-01

    Full Text Available Metastatic complications are responsible for more than 90% of cancer related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multi-step process, with each step involving intricate cross-talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM. Many ECM proteins are significantly de-regulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.

  5. Multiple-Targeted Graphene-based Nanocarrier for Intracellular Imaging of mRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ying; Li, Zhaohui; Liu, Misha; Hu, Dehong; Lin, Yuehe; Li, Jinghong

    2017-08-29

    Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labeled single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis.

  6. Targeting the epigenome with bioactive food components for cancer prevention.

    Science.gov (United States)

    Ong, Thomas Prates; Moreno, Fernando Salvador; Ross, Sharon Ann

    2011-01-01

    Epigenetic processes participate in cancer development and likely influence cancer prevention. Global DNA hypomethylation, gene promoter hypermethylation and aberrant histone post-translational modifications are hallmarks of neoplastic cells which have been associated with genomic instability and altered gene expression. Because epigenetic deregulation occurs early in carcinogenesis and is potentially reversible, intervention strategies targeting the epigenome have been proposed for cancer prevention. Bioactive food components (BFCs) with anticancer potential, including folate, polyphenols, selenium, retinoids, fatty acids, isothiocyanates and allyl compounds, influence DNA methylation and histone modification processes. Such activities have been shown to affect the expression of genes involved in cell proliferation, death and differentiation that are frequently altered in cancer. Although the epigenome represents a promising target for cancer prevention with BFCs, few studies have addressed the influence of dietary components on these mechanisms in vivo, particularly on the phenotype of humans, and thus the exact mechanisms whereby diet mediates an effect on cancer prevention remains unclear. Primary factors that should be elucidated include the effective doses and dose timing of BFCs to attain epigenetic effects. Because diet-epigenome interactions are likely to occur in utero, the impact of early-life nutrition on cancer risk programming should be further investigated. Copyright © 2012 S. Karger AG, Basel.

  7. New Advances in Nanotechnology-Based Diagnosis and Therapeutics for Breast Cancer: An Assessment of Active-Targeting Inorganic Nanoplatforms.

    Science.gov (United States)

    Falagan-Lotsch, Priscila; Grzincic, Elissa M; Murphy, Catherine J

    2017-01-18

    Breast cancer is a major cause of suffering and mortality among women. Limitations in the current diagnostic methods and treatment approaches have led to new strategies to positively impact the survival rates and quality of life of breast cancer patients. Nanotechnology offers a real possibility of mitigating breast cancer mortality by early-stage cancer detection and more precise diagnosis as well as more effective treatments with minimal side effects. The current nanoplatforms approved for breast cancer therapeutics are based on passive tumor targeting using organic nanoparticles and have not provided the expected significant improvements in the clinic. In this review, we present the emerging approaches in breast cancer nanomedicine based on active targeting using versatile inorganic nanoplatforms with biomedical relevance, such as gold, silica, and iron oxide nanoparticles, as well as their efficacy in breast cancer imaging, drug and gene delivery, thermal therapy, combinational therapy, and theranostics in preclinical studies. The main challenges for clinical translation and perspectives are discussed.

  8. Developing Targeted Hybrid Imaging Probes by Chelator Scaffolding.

    Science.gov (United States)

    Summer, Dominik; Grossrubatscher, Leo; Petrik, Milos; Michalcikova, Tereza; Novy, Zbynek; Rangger, Christine; Klingler, Maximilian; Haas, Hubertus; Kaeopookum, Piriya; von Guggenberg, Elisabeth; Haubner, Roland; Decristoforo, Clemens

    2017-06-21

    Positron emission tomography (PET) as well as optical imaging (OI) with peptide receptor targeting probes have proven their value for oncological applications but also show restrictions depending on the clinical field of interest. Therefore, the combination of both methods, particularly in a single molecule, could improve versatility in clinical routine. This proof of principle study aims to show that a chelator, Fusarinine C (FSC), can be utilized as scaffold for novel dimeric dual-modality imaging agents. Two targeting vectors (a minigastrin analogue (MG11) targeting cholecystokinin-2 receptor overexpression (CCK2R) or integrin α V β 3 targeting cyclic pentapeptides (RGD)) and a near-infrared fluorophore (Sulfo-Cyanine7) were conjugated to FSC. The probes were efficiently labeled with gallium-68 and in vitro experiments including determination of logD, stability, protein binding, cell binding, internalization, and biodistribution studies as well as in vivo micro-PET/CT and optical imaging in U-87MG α V β 3 - and A431-CCK2R expressing tumor xenografted mice were carried out. Novel bioconjugates showed high receptor affinity and highly specific targeting properties at both receptors. Ex vivo biodistribution and micro-PET/CT imaging studies revealed specific tumor uptake accompanied by slow blood clearance and retention in nontargeted tissues (spleen, liver, and kidneys) leading to visualization of tumors at early (30 to 120 min p.i.). Excellent contrast in corresponding optical imaging studies was achieved especially at delayed time points (24 to 72 h p.i.). Our findings show the proof of principle of chelator scaffolding for hybrid imaging agents and demonstrate FSC being a suitable bifunctional chelator for this approach. Improvements to fine-tune pharmacokinetics are needed to translate this into a clinical setting.

  9. 2'-Hydroxyflavanone: A novel strategy for targeting breast cancer.

    Science.gov (United States)

    Singhal, Jyotsana; Nagaprashantha, Lokesh; Chikara, Shireen; Awasthi, Sanjay; Horne, David; Singhal, Sharad S

    2017-09-26

    Breast cancer is the most common cancer in women that is driven by cross-talk with hormonal and cellular signaling pathways. The natural phytochemicals, due to broad-spectrum anti-inflammatory and anti-cancerous properties, present with novel opportunities for targeting breast cancer. Intake of citrus fruits is known to reduce the risk for incidence of breast cancer. Hence, we tested the efficacy of citrus flavonoid 2'-hydroxyflavanone (2HF) in breast cancer. 2HF inhibited survival, clonogenic ability, cell cycle progression and induced apoptosis in breast cancer cells. 2HF also decreased VEGF levels and inhibited migratory capacity of breast cancer cells. Administration of 2HF led to regression of triple-negative MDA-MB-231 tumors in the mice xenograft model. 2HF decreased the levels of RLIP76 both in vitro studies and in vivo MDA-MB-231 xenograft model of breast cancer. Western blot and histopathological analyses of resected tumors showed a decline in the levels of survival and proliferation markers Ki67, pAkt, survivin, and cell cycle proteins CDK4 and cyclin B1. 2HF treatment led to inhibition of angiogenesis as determined by decreased VEGF levels in vitro and angiogenesis marker CD31 in vivo . 2HF reversed the pro-/anti-apoptotic ratio of BAX/BCL-2 by decreasing anti-apoptotic protein BCL-2 and increasing pro-apoptotic proteins BAX and BIM in vivo . 2HF also decreased the mesenchymal markers vimentin and fibronectin along with causing a parallel increase in pro-differentiation protein E-cadherin. Collectively, the ability of 2HF to decrease RLIP76, VEGF and regulate critical proliferative, apoptotic and differentiation proteins together provides strong rationale to further develop 2HF based interventions for targeting breast cancer.

  10. Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

    Science.gov (United States)

    2017-10-01

    relevance to targeted therapies. Our overarching goal is to more effectively bring novel agents and new biomarker driven trials directly to patients...direct relevance to targeted therapies. Our overarching goal is to more effectively bring novel agents and new biomarker driven trials directly to...al: Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device . PLoS One 7:e35976, 2012 21

  11. THz-SAR Vibrating Target Imaging via the Bayesian Method

    Directory of Open Access Journals (Sweden)

    Bin Deng

    2017-01-01

    Full Text Available Target vibration bears important information for target recognition, and terahertz, due to significant micro-Doppler effects, has strong advantages for remotely sensing vibrations. In this paper, the imaging characteristics of vibrating targets with THz-SAR are at first analyzed. An improved algorithm based on an excellent Bayesian approach, that is, the expansion-compression variance-component (ExCoV method, has been proposed for reconstructing scattering coefficients of vibrating targets, which provides more robust and efficient initialization and overcomes the deficiencies of sidelobes as well as artifacts arising from the traditional correlation method. A real vibration measurement experiment of idle cars was performed to validate the range model. Simulated SAR data of vibrating targets and a tank model in a real background in 220 GHz show good performance at low SNR. Rapidly evolving high-power terahertz devices will offer viable THz-SAR application at a distance of several kilometers.

  12. Molecular MR imaging of cancer gene therapy. Ferritin transgene reporter takes the stage

    International Nuclear Information System (INIS)

    Hasegawa, Sumitaka; Furukawa, Takako; Saga, Tsuneo

    2010-01-01

    Molecular imaging using magnetic resonance (MR) imaging has been actively investigated and made rapid progress in the past decade. Applied to cancer gene therapy, the technique's high spatial resolution allows evaluation of gene delivery into target tissues. Because noninvasive monitoring of the duration, location, and magnitude of transgene expression in tumor tissues or cells provides useful information for assessing therapeutic efficacy and optimizing protocols, molecular imaging is expected to become a critical step in the success of cancer gene therapy in the near future. We present a brief overview of the current status of molecular MR imaging, especially in vivo reporter gene imaging using ferritin and other reporters, discuss its application to cancer gene therapy, and present our research of MR imaging detection of electroporation-mediated cancer gene therapy using the ferritin reporter gene. (author)

  13. Identifying molecular targets of lifestyle modifications in colon cancer prevention

    Directory of Open Access Journals (Sweden)

    Molly Marie Derry

    2013-05-01

    Full Text Available One in four deaths in the United States is cancer-related, and colorectal cancer (CRC is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; ~20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological and behavioral processes that could positively influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.

  14. Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies.

    Science.gov (United States)

    Iurescia, Sandra; Fioretti, Daniela; Rinaldi, Monica

    2018-01-01

    The innate immune system provides the first line of defense against pathogen infection though also influences pathways involved in cancer immunosurveillance. The innate immune system relies on a limited set of germ line-encoded sensors termed pattern recognition receptors (PRRs), signaling proteins and immune response factors. Cytosolic receptors mediate recognition of danger damage-associated molecular patterns (DAMPs) signals. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Recent studies revealed that PRRs respond to nucleic acids (NA) released by dying, damaged, cancer cells, as danger DAMPs signals, and presence of signaling proteins across cancer types suggests that these signaling mechanisms may be involved in cancer biology. DAMPs play important roles in shaping adaptive immune responses through the activation of innate immune cells and immunological response to danger DAMPs signals is crucial for the host response to cancer and tumor rejection. Furthermore, PRRs mediate the response to NA in several vaccination strategies, including DNA immunization. As route of double-strand DNA intracellular entry, DNA immunization leads to expression of key components of cytosolic NA-sensing pathways. The involvement of NA-sensing mechanisms in the antitumor response makes these pathways attractive drug targets. Natural and synthetic agonists of NA-sensing pathways can trigger cell death in malignant cells, recruit immune cells, such as DCs, CD8 + T cells, and NK cells, into the tumor microenvironment and are being explored as promising adjuvants in cancer immunotherapies. In this minireview, we discuss how cGAS-STING and RIG-I-MAVS pathways have been targeted for cancer treatment in preclinical translational researches. In addition, we present a targeted selection of recent clinical trials employing agonists of cytosolic NA-sensing pathways showing how these pathways

  15. Targeting Mcl-1 for Radiosensitization of Pancreatic Cancers

    Directory of Open Access Journals (Sweden)

    Dongping Wei

    2015-02-01

    Full Text Available In order to identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer, we previously conducted an RNAi library screen of 8,800 genes. We identified Mcl-1 (myeloid cell leukemia-1, an anti-apoptotic member of the Bcl-2 family, as a target for sensitizing pancreatic cancer cells to chemoradiation. In the present study we investigated Mcl-1 inhibition by either genetic or pharmacological approaches as a radiosensitizing strategy in pancreatic cancer cells. Mcl-1 depletion by siRNA produced significant radiosensitization in BxPC-3 and Panc-1 cells in association with Caspase-3 activation and PARP cleavage, but only minimal radiosensitization in MiaPaCa-2 cells. We next tested the ability of the recently identified, selective, small molecule inhibitor of Mcl-1, UMI77, to radiosensitize in pancreatic cancer cells. UMI77 caused dissociation of Mcl-1 from the pro-apoptotic protein Bak and produced significant radiosensitization in BxPC-3 and Panc-1 cells, but minimal radiosensitization in MiaPaCa-2 cells. Radiosensitization by UMI77 was associated with Caspase-3 activation and PARP cleavage. Importantly, UMI77 did not radiosensitize normal small intestinal cells. In contrast, ABT-737, an established inhibitor of Bcl-2, Bcl-XL, and Bcl-w, failed to radiosensitize pancreatic cancer cells suggesting the unique importance of Mcl-1 relative to other Bcl-2 family members to radiation survival in pancreatic cancer cells. Taken together, these results validate Mcl-1 as a target for radiosensitization of pancreatic cancer cells and demonstrate the ability of small molecules which bind the canonical BH3 groove of Mcl-1, causing displacement of Mcl-1 from Bak, to selectively radiosensitize pancreatic cancer cells.

  16. Breast cancer stem cells, EMT and therapeutic targets

    Energy Technology Data Exchange (ETDEWEB)

    Kotiyal, Srishti; Bhattacharya, Susinjan, E-mail: s.bhattacharya@jiit.ac.in

    2014-10-10

    Highlights: • Therapeutic targeting or inhibition of the key molecules of signaling pathways can control growth of breast cancer stem cells (BCSCs). • Development of BCSCs also involves miRNA interactions. • Therapeutic achievement can be done by targeting identified targets in the BCSC pathways. - Abstract: A small heterogeneous population of breast cancer cells acts as seeds to induce new tumor growth. These seeds or breast cancer stem cells (BCSCs) exhibit great phenotypical plasticity which allows them to undergo “epithelial to mesenchymal transition” (EMT) at the site of primary tumor and a future reverse transition. Apart from metastasis they are also responsible for maintaining the tumor and conferring it with drug and radiation resistance and a tendency for post-treatment relapse. Many of the signaling pathways involved in induction of EMT are involved in CSC generation and regulation. Here we are briefly reviewing the mechanism of TGF-β, Wnt, Notch, TNF-α, NF-κB, RTK signalling pathways which are involved in EMT as well as BCSCs maintenance. Therapeutic targeting or inhibition of the key/accessory players of these pathways could control growth of BCSCs and hence malignant cancer. Additionally several miRNAs are dysregulated in cancer stem cells indicating their roles as oncogenes or tumor suppressors. This review also lists the miRNA interactions identified in BCSCs and discusses on some newly identified targets in the BCSC regulatory pathways like SHIP2, nicastrin, Pin 1, IGF-1R, pro-inflammatory cytokines and syndecan which can be targeted for therapeutic achievements.

  17. Breast cancer stem cells, EMT and therapeutic targets

    International Nuclear Information System (INIS)

    Kotiyal, Srishti; Bhattacharya, Susinjan

    2014-01-01

    Highlights: • Therapeutic targeting or inhibition of the key molecules of signaling pathways can control growth of breast cancer stem cells (BCSCs). • Development of BCSCs also involves miRNA interactions. • Therapeutic achievement can be done by targeting identified targets in the BCSC pathways. - Abstract: A small heterogeneous population of breast cancer cells acts as seeds to induce new tumor growth. These seeds or breast cancer stem cells (BCSCs) exhibit great phenotypical plasticity which allows them to undergo “epithelial to mesenchymal transition” (EMT) at the site of primary tumor and a future reverse transition. Apart from metastasis they are also responsible for maintaining the tumor and conferring it with drug and radiation resistance and a tendency for post-treatment relapse. Many of the signaling pathways involved in induction of EMT are involved in CSC generation and regulation. Here we are briefly reviewing the mechanism of TGF-β, Wnt, Notch, TNF-α, NF-κB, RTK signalling pathways which are involved in EMT as well as BCSCs maintenance. Therapeutic targeting or inhibition of the key/accessory players of these pathways could control growth of BCSCs and hence malignant cancer. Additionally several miRNAs are dysregulated in cancer stem cells indicating their roles as oncogenes or tumor suppressors. This review also lists the miRNA interactions identified in BCSCs and discusses on some newly identified targets in the BCSC regulatory pathways like SHIP2, nicastrin, Pin 1, IGF-1R, pro-inflammatory cytokines and syndecan which can be targeted for therapeutic achievements

  18. uPAR Targeted Radionuclide Therapy with 177Lu-DOTA-AE105 Inhibits Dissemination of Metastatic Prostate Cancer

    DEFF Research Database (Denmark)

    Persson, Morten; Juhl, Karina; Rasmussen, Palle

    2014-01-01

    The urokinase-type plasminogen activator receptor (uPAR) is implicated in cancer invasion and metastatic development in prostate cancer and provides therefore an attractive molecular target for both imaging and therapy. In this study, we provide the first in vivo data on an antimetastatic effect...... of uPAR radionuclide targeted therapy in such lesions and show the potential of uPAR positron emission tomography (PET) imaging for identifying small foci of metastatic cells in a mouse model of disseminating human prostate cancer. Two radiolabeled ligands were generated in high purity and specific...... value of 100 nM in a competitive binding experiment. In vivo, uPAR targeted radionuclide therapy significantly reduced the number of metastatic lesions in the disseminated metastatic prostate cancer model, when compared to vehicle and nontargeted 177Lu groups (p

  19. Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Huang J

    2016-07-01

    Full Text Available Jing Huang,1,2 Weiping Qian,3 Liya Wang,1,2 Hui Wu,1 Hongyu Zhou,3 Andrew Yongqiang Wang,4 Hongbo Chen,5 Lily Yang,3 Hui Mao1,2 1Department of Radiology and Imaging Sciences, 2Center for Systems Imaging, 3Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA; 4Ocean Nanotech LLC, Springdale, AR, USA; 5School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin, Guangxi, People’s Republic of China Abstract: Engineered nanocarriers have emerged as a promising platform for cancer therapy. However, the therapeutic efficacy is limited by low drug loading efficiency, poor passive targeting to tumors, and severe systemic side effects. Herein, we report a new class of nanoconstructs based on milk protein (casein-coated magnetic iron oxide (CNIO nanoparticles for targeted and image-guided pancreatic cancer treatment. The tumor-targeting amino-terminal fragment (ATF of urokinase plasminogen activator and the antitumor drug cisplatin (CDDP were engineered on this nanoplatform. High drug loading (~25 wt% and sustained release at physiological conditions were achieved through the exchange and encapsulation strategy. These ATF-CNIO-CDDP nanoparticles demonstrated actively targeted delivery of CDDP to orthotopic pancreatic tumors in mice. The effective accumulation and distribution of ATF-CNIO-CDDP was evidenced by magnetic resonance imaging, based on the T2-weighted contrast resulting from the specific accumulation of ATF-CNIO-CDDP in the tumor. Actively targeted delivery of ATF-CNIO-CDDP led to improved therapeutic efficacy in comparison with free CDDP and nontargeted CNIO-CDDP treatment. Meanwhile, less systemic side effects were observed in the nanocarrier-treated groups than that in the group treated with free CDDP. Hematoxylin and Eosin and Sirius Red staining of tumor sections revealed the possible disruption of stroma during the treatment with ATF-CNIO-CDDP. Overall, our results suggest that

  20. A PCA3 gene-based transcriptional amplification system targeting primary prostate cancer

    OpenAIRE

    Neveu, Bertrand; Jain, Pallavi; T?tu, Bernard; Wu, Lily; Fradet, Yves; Pouliot, Fr?d?ric

    2015-01-01

    Targeting specifically primary prostate cancer (PCa) cells for immune therapy, gene therapy or molecular imaging is of high importance. The PCA3 long non-coding RNA is a unique PCa biomarker and oncogene that has been widely studied. This gene has been mainly exploited as an accurate diagnostic urine biomarker for PCa detection. In this study, the PCA3 promoter was introduced into a new transcriptional amplification system named the 3-Step Transcriptional Amplification System (PCA3-3STA) and ...

  1. Designing the nanobiointerface of fluorescent nanodiamonds: highly selective targeting of glioma cancer cells.

    Science.gov (United States)

    Slegerova, Jitka; Hajek, Miroslav; Rehor, Ivan; Sedlak, Frantisek; Stursa, Jan; Hruby, Martin; Cigler, Petr

    2015-01-14

    Core-shell nanoparticles based on fluorescent nanodiamonds coated with a biocompatible N-(2-hydroxypropyl)methacrylamide copolymer shell were developed for background-free near-infrared imaging of cancer cells. The particles showed excellent colloidal stability in buffers and culture media. After conjugation with a cyclic RGD peptide they selectively targeted integrin αvβ3 receptors on glioblastoma cells with high internalization efficacy.

  2. Target plane imaging system for the Nova laser

    International Nuclear Information System (INIS)

    Swift, C.D.; Bliss, E.S.; Jones, W.A.; Reeves, R.J.; Seppala, L.G.; Shelton, R.T.; VanArsdall, P.J.

    1985-01-01

    The Nova laser, in operation since December 1984, is capable of irradiating targets with light at 1.05 μm, 0.53 μm, and 0.35 μm. Correct alignment of these harmonic beams uses a system called a target plane imager (TPI). It is a large microscope (four meters long, weighing one thousand kilograms) that relays images from the target chamber center to a video optics module located on the outside of the chamber. Several modes of operation are possible including: near-field viewing and far-field viewing at three magnifications and three wavelengths. In addition, the entire instrument can be scanned in X,Y,Z to examine various planes near chamber center. Performance of this system and its computer controls will be described

  3. New perspectives on targeted therapy in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Coward JIG

    2015-02-01

    Full Text Available Jermaine IG Coward,1–3 Kathryn Middleton,1 Felicity Murphy1 1Mater Health Services, Raymond Terrace, South Brisbane, QLD, Australia; 2Inflammtion and Cancer Therapeutics Group, Mater Research, University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, QLD, Australia; 3School of Medicine, University of Queensland, Brisbane, QLD, Australia Abstract: Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5 year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Although changes to the scheduling and administration of chemotherapy have improved outcomes to a degree, a therapeutic ceiling is being reached with this approach, resulting in a number of trials investigating the efficacy of targeted therapies alongside standard treatment algorithms. Furthermore, there is an urge to develop subtype-specific studies in an attempt to improve outcomes, which currently remain poor. This review summarizes the key studies with antiangiogenic agents, poly(adenosine diphosphate [ADP]-ribose inhibitors, and epidermal growth factor receptor/human epidermal growth factor receptor family targeting, in addition to folate receptor antagonists and insulin growth factor receptor inhibitors. The efficacy of treatment paradigms used in non-ovarian malignancies for type I tumors is also highlighted, in addition to recent advances in appropriate patient stratification for targeted therapies in epithelial ovarian cancer. Keywords: antiangiogenic therapy, high-grade serous, low grade ovarian cancer, PARP inhibition, cancer-related inflammation

  4. Rational design of non-resistant targeted cancer therapies

    Science.gov (United States)

    Martínez-Jiménez, Francisco; Overington, John P.; Al-Lazikani, Bissan; Marti-Renom, Marc A.

    2017-01-01

    Drug resistance is one of the major problems in targeted cancer therapy. A major cause of resistance is changes in the amino acids that form the drug-target binding site. Despite of the numerous efforts made to individually understand and overcome these mutations, there is a lack of comprehensive analysis of the mutational landscape that can prospectively estimate drug-resistance mutations. Here we describe and computationally validate a framework that combines the cancer-specific likelihood with the resistance impact to enable the detection of single point mutations with the highest chance to be responsible of resistance to a particular targeted cancer therapy. Moreover, for these treatment-threatening mutations, the model proposes alternative therapies overcoming the resistance. We exemplified the applicability of the model using EGFR-gefitinib treatment for Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Cancer (LSCC) and the ERK2-VTX11e treatment for melanoma and colorectal cancer. Our model correctly identified the phenotype known resistance mutations, including the classic EGFR-T790M and the ERK2-P58L/S/T mutations. Moreover, the model predicted new previously undescribed mutations as potentially responsible of drug resistance. Finally, we provided a map of the predicted sensitivity of alternative ERK2 and EGFR inhibitors, with a particular highlight of two molecules with a low predicted resistance impact. PMID:28436422

  5. Evaluation of the Efficacy of Targeted Imaging Agents

    Science.gov (United States)

    Graham, Michael M.; Weber, Wolfgang A.

    2016-01-01

    This paper presents our adaptation of Fryback and Thornbury’s hierarchical scheme for modeling the efficacy of diagnostic imaging systems. The original scheme was designed to evaluate new medical imaging systems but is less successful when applied to evaluate new radiopharmaceuticals. The proposed adaptation, which is specifically directed toward evaluating targeted imaging agents, has 6 levels: in vitro characterization, in vivo animal studies, initial human studies, impact on clinical care (change in management), impact on patient outcome, and societal efficacy. These levels, particularly the first four, implicitly define the sequence of studies needed to move an agent from the radiochemistry synthesis laboratory to the clinic. Completion of level 4 (impact on clinical care) should be sufficient for initial approval and reimbursement. We hope that the adapted scheme will help streamline the process and assist in bringing new targeted radiopharmaceuticals to approval over the next few years. PMID:26769867

  6. Cancer stem cells, the ultimate targets in cancer therapy

    Directory of Open Access Journals (Sweden)

    Shabbir A

    2018-01-01

    Full Text Available Ahmed Shabbir,1 Tuba Esfandyari,2 Faris Farassati1,3,4 1Midwest Biomedical Research Foundation, Kansas City Veterans Affairs Medical Center, 2Department of Medicine, School of Medicine, The University of Kansas, 3Saint Luke’s Cancer Institute, 4Saint Luke’s Marion Bloch Neuroscience Institute, Saint Luke’s Health System, Kansas City, MO, USAThe concept of cancer stem cells (CSCs is currently of significant interest due to its important implications in our understanding of the tumor biology as well as development of novel cancer therapeutics. Tumors, in resemblance to normal organs, contain pluripotential cells that can generate their own kind as well as cells that can further differentiate. CSCs are thought to be highly resistant to the cytotoxic effects of conventional cancer therapy regimens,1 which leads to the rise of a refractory status in tumors.1,2 Therefore, CSCs can be considered as the main drivers of tumor integrity and function. This resembles the role of normal stem cells in tissue and organ development. Therapeutic assaults that eliminate differentiated cancer cells while leaving CSCs, therefore, are doomed to fail due to the resistance of CSCs and their ability to repopulate the tumor.3 This phenomenon is indeed observed in the clinic routinely. Clinical response to a chemotherapy regimen is reduced over time as the tumor enters a refractory stage induced by enrichment of CSCs in the tumor cell population. This is even observed in cells cultured from a patient at early stage of the disease, such as in colorectal cancer (SW480, ATCC CCL-228, and recurrence of the malignancy results in a wide-spread metastasis (SW620, ATCC CCL-227. The SW260 shows a significantly higher percentage of cells positive for CD133, a marker for CSCs (data from our team. Methods for the detection of CSCs include surface markers such as CD24, CD34, CD44, CD44, CD90, CD133, ABCB5, and EpCAM that have been shown to indicate CSC subpopulations in a range

  7. TARCC: Targeting Alpha-Radionuclide to Combat Cancer

    International Nuclear Information System (INIS)

    Barbet, J.; Cherel, M.; Maecke, H.; Senekowitsch-Schmidtke, R.; Meyer, G.; Forssell-Aronsson, E.; Gmeiner Stopar, T.; Montavon, G.; Bruchertseifer, F.; Lambert, B.; Joseph-Mathieu, P.

    2009-01-01

    Cancer is a human health problem with many unmet needs. Today treatments mainly rely on surgery, external beam radiation and chemotherapy to remove or destroy bulky tumours. However, they cannot permanently treat all cancer and relapse occurs in up to 50% of the patients' population. Targeted radionuclide therapy (TRT) offers an alternative with unlikely cross-resistance with established therapies to treat small size tumours (residual disease, micro metastases). In contrast to beta radionuclides, alpha-emitting radionuclides seem particularly promising to selectively destroy disseminated cancer cells, due to their decay characteristics. The challenge remains to deliver the radioactive atoms fast and efficiently enough and to find the right balance between toxicity and anti-tumour effect. The TARCC project proposes a concerted and multidisciplinary action plan to develop targeted alpha-radionuclide therapy to: - Improve the access to the most promising alpha-emitting radionuclides. - Test in appropriate preclinical models new radiolabelling methods and new biological vectors to target the radionuclides to cancer cells in vivo. - Compare the results obtained with the different vectors (antibodies, peptides, amino- acids or nanocolloids) in different preclinical tumour models. - Evaluate short-term and long-term treatment toxicity and dosimetry at both macroscopic and microscopic levels. It is expected that this network approach will make it possible to select several candidates for future preclinical and clinical developments and to define the most promising settings for targeted alpha-radionuclide therapy in terms of vector properties and modes of administration. (author)

  8. Targeted Therapies for Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Vyshak Alva Venur

    2016-09-01

    Full Text Available The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2 and epidermal growth factor receptor (EGFR, vascular endothelial growth factor (VEGF receptor, mechanistic target of rapamycin (mTOR pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6 pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%–30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

  9. Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

    DEFF Research Database (Denmark)

    Salanti, Ali; Clausen, Thomas M.; Agerbæk, Mette Ø.

    2015-01-01

    be specifically targeted by recombinant VAR2CSA (rVAR2). In tumors, placental-like CS chains are linked to a limited repertoire of cancer-associated proteoglycans including CD44 and CSPG4. The rVAR2 protein localizes to tumors in vivo and rVAR2 fused to diphtheria toxin or conjugated to hemiasterlin compounds...

  10. Y-Trap Cancer Immunotherapy Drug Targets Two Proteins

    Science.gov (United States)

    Two groups of researchers, working independently, have fused a TGF-beta receptor to a monoclonal antibody that targets a checkpoint protein. The result, this Cancer Currents blog describes, is a single hybrid molecule called a Y-trap that blocks two pathways used by tumors to evade the immune system.

  11. Toward integrative cancer immunotherapy: targeting the tumor microenvironment.

    Science.gov (United States)

    Emens, Leisha A; Silverstein, Samuel C; Khleif, Samir; Marincola, Francesco M; Galon, Jérôme

    2012-04-10

    The development of cancer has historically been attributed to genomic alterations of normal host cells. Accordingly, the aim of most traditional cancer therapies has been to destroy the transformed cells themselves. There is now widespread appreciation that the progressive growth and metastatic spread of cancer cells requires the cooperation of normal host cells (endothelial cells, fibroblasts, other mesenchymal cells, and immune cells), both local to, and at sites distant from, the site at which malignant transformation occurs. It is the balance of these cellular interactions that both determines the natural history of the cancer, and influences its response to therapy. This active tumor-host dynamic has stimulated interest in the tumor microenvironment as a key target for both cancer diagnosis and therapy. Recent data has demonstrated both that the presence of CD8⁺ T cells within a tumor is associated with a good prognosis, and that the eradication of all malignantly transformed cells within a tumor requires that the intra-tumoral concentration of cytolytically active CD8⁺ effector T cells remain above a critical concentration until every tumor cell has been killed. These findings have stimulated two initiatives in the field of cancer immunotherapy that focus on the tumor microenvironment. The first is the development of the immune score as part of the routine diagnostic and prognostic evaluation of human cancers, and the second is the development of combinatorial immune-based therapies that reduce tumor-associated immune suppression to unleash pre-existing or therapeutically-induced tumor immunity. In support of these efforts, the Society for the Immunotherapy of Cancer (SITC) is sponsoring a workshop entitled "Focus on the Target: The Tumor Microenvironment" to be held October 24-25, 2012 in Bethesda, Maryland. This meeting should support development of the immune score, and result in a position paper highlighting opportunities for the development of

  12. Ornithine decarboxylase as a therapeutic target for endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Hong Im Kim

    Full Text Available Ornithine Decarboxylase (ODC a key enzyme in polyamine biosynthesis is often overexpressed in cancers and contributes to polyamine-induced cell proliferation. We noted ubiquitous expression of ODC1 in our published endometrial cancer gene array data and confirmed this in the cancer genome atlas (TCGA with highest expression in non-endometrioid, high grade, and copy number high cancers, which have the worst clinical outcomes. ODC1 expression was associated with worse overall survival and increased recurrence in three endometrial cancer gene expression datasets. Importantly, we confirmed these findings using quantitative real-time polymerase chain reaction (qRT-PCR in a validation cohort of 60 endometrial cancers and found that endometrial cancers with elevated ODC1 had significantly shorter recurrence-free intervals (KM log-rank p = 0.0312, Wald test p = 5.59e-05. Difluoromethylornithine (DFMO a specific inhibitor of ODC significantly reduced cell proliferation, cell viability, and colony formation in cell line models derived from undifferentiated, endometrioid, serous, carcinosarcoma (mixed mesodermal tumor; MMT and clear cell endometrial cancers. DFMO also significantly reduced human endometrial cancer ACI-98 tumor burden in mice compared to controls (p = 0.0023. ODC-regulated polyamines (putrescine [Put] and/or spermidine [Spd] known activators of cell proliferation were strongly decreased in response to DFMO, in both tumor tissue ([Put] (p = 0.0006, [Spd] (p<0.0001 and blood plasma ([Put] (p<0.0001, [Spd] (p = 0.0049 of treated mice. Our study indicates that some endometrial cancers appear particularly sensitive to DFMO and that the polyamine pathway in endometrial cancers in general and specifically those most likely to suffer adverse clinical outcomes could be targeted for effective treatment, chemoprevention or chemoprevention of recurrence.

  13. Targeting HER2-positive cancer using multifunctional nanoparticles

    DEFF Research Database (Denmark)

    Juul, Christian Ammitzbøll

    efficiency, is thoroughly reviewed. Chapter 4 encompasses a comprehensive manuscript, which describes the in vitro and in vivo evaluation of a novel liposomal delivery platform designed to target the HER2 receptor on cancer cells and be activated by enzyme activity in the tumor. In Chapter 5, an alternative......Advanced delivery of chemotherapeutics to tumor tissue is an active field of research, as it offers several benefits over conventional cancer therapies. In the three introductory chapters of this thesis, the development of liposomes as drug carriers, including novel strategies to improve delivery...... HER2-targeted liposome formulation was assessed in vitro. Rather than being enzyme-sensitive, these liposomes were responsive to reducing conditions. Such conditions are found in several cancers due to hypoxia as well as in endocytic compartments. The progressive in vitro optimization of a complex...

  14. Cancer Nanomedicine: From Targeted Delivery to Combination Therapy

    Science.gov (United States)

    Xu, Xiaoyang; Ho, William; Zhang, Xueqing; Bertrand, Nicolas; Farokhzad, Omid

    2015-01-01

    The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of a variety of diseases, including cancer. The unique properties of nanoparticles, such as large surface-to volume ratio, small size, the ability to encapsulate a variety of drugs, and tunable surface chemistry, gives them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make nanoparticles a mode of treatment potentially superior to conventional cancer therapies. This article highlights the most recent developments in cancer treatment using nanoparticles as drug-delivery vehicles, including promising opportunities in targeted and combination therapy. PMID:25656384

  15. Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ross C. Smith

    2011-04-01

    Full Text Available Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting ve