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Sample records for bicap tumor probe

  1. Imaging probe for tumor malignancy

    NASA Astrophysics Data System (ADS)

    Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Hasahiro

    2009-02-01

    Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions ("tumor hypoxia"). Although more than half a century has passed since it was suggested that tumor hypoxia correlated with poor treatment outcomes and contributed to cancer recurrence, a fundamental solution to this problem has yet to be found. Hypoxia-inducible factor (HIF-1) is the main transcription factor that regulates the cellular response to hypoxia. It induces various genes whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important targets of cancer therapy, particularly in therapy against refractory cancers. Imaging of the HIF-1-active microenvironment is therefore important for cancer therapy. To image HIF-1activity in vivo, we developed a PTD-ODD fusion protein, POHA, which was uniquely labeled with near-infrared fluorescent dye at the C-terminal. POHA has two functional domains: protein transduction domain (PTD) and VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of the alpha subunit of HIF-1 (HIF-1α). It can therefore be delivered to the entire body and remain stabilized in the HIF-1-active cells. When it was intravenously injected into tumor-bearing mice, a tumor-specific fluorescence signal was detected in the tumor 6 h after the injection. These results suggest that POHA can be used an imaging probe for tumor malignancy.

  2. Protein-based tumor molecular imaging probes

    PubMed Central

    Lin, Xin; Xie, Jin

    2013-01-01

    Molecular imaging is an emerging discipline which plays critical roles in diagnosis and therapeutics. It visualizes and quantifies markers that are aberrantly expressed during the disease origin and development. Protein molecules remain to be one major class of imaging probes, and the option has been widely diversified due to the recent advances in protein engineering techniques. Antibodies are part of the immunosystem which interact with target antigens with high specificity and affinity. They have long been investigated as imaging probes and were coupled with imaging motifs such as radioisotopes for that purpose. However, the relatively large size of antibodies leads to a half-life that is too long for common imaging purposes. Besides, it may also cause a poor tissue penetration rate and thus compromise some medical applications. It is under this context that various engineered protein probes, essentially antibody fragments, protein scaffolds, and natural ligands have been developed. Compared to intact antibodies, they possess more compact size, shorter clearance time, and better tumor penetration. One major challenge of using protein probes in molecular imaging is the affected biological activity resulted from random labeling. Site-specific modification, however, allows conjugation happening in a stoichiometric fashion with little perturbation of protein activity. The present review will discuss protein-based probes with focus on their application and related site-specific conjugation strategies in tumor imaging. PMID:20232092

  3. FISHtrees 3.0: Tumor Phylogenetics Using a Ploidy Probe

    PubMed Central

    Chowdhury, Salim Akhter; Lee, Woei-Jyh; Wangsa, Darawalee; Heselmeyer-Haddad, Kerstin; Ried, Thomas; Schwartz, Russell; Schäffer, Alejandro A.

    2016-01-01

    Advances in fluorescence in situ hybridization (FISH) make it feasible to detect multiple copy-number changes in hundreds of cells of solid tumors. Studies using FISH, sequencing, and other technologies have revealed substantial intra-tumor heterogeneity. The evolution of subclones in tumors may be modeled by phylogenies. Tumors often harbor aneuploid or polyploid cell populations. Using a FISH probe to estimate changes in ploidy can guide the creation of trees that model changes in ploidy and individual gene copy-number variations. We present FISHtrees 3.0, which implements a ploidy-based tree building method based on mixed integer linear programming (MILP). The ploidy-based modeling in FISHtrees includes a new formulation of the problem of merging trees for changes of a single gene into trees modeling changes in multiple genes and the ploidy. When multiple samples are collected from each patient, varying over time or tumor regions, it is useful to evaluate similarities in tumor progression among the samples. Therefore, we further implemented in FISHtrees 3.0 a new method to build consensus graphs for multiple samples. We validate FISHtrees 3.0 on a simulated data and on FISH data from paired cases of cervical primary and metastatic tumors and on paired breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Tests on simulated data show improved accuracy of the ploidy-based approach relative to prior ploidyless methods. Tests on real data further demonstrate novel insights these methods offer into tumor progression processes. Trees for DCIS samples are significantly less complex than trees for paired IDC samples. Consensus graphs show substantial divergence among most paired samples from both sets. Low consensus between DCIS and IDC trees may help explain the difficulty in finding biomarkers that predict which DCIS cases are at most risk to progress to IDC. The FISHtrees software is available at ftp://ftp.ncbi.nih.gov/pub/FISHtrees. PMID

  4. Probing model tumor interfacial properties using piezoelectric cantilevers

    PubMed Central

    Yegingil, Hakki; Shih, Wan Y.; Shih, Wei-Heng

    2010-01-01

    Invasive malignant breast cancers are typically branchy and benign breast tumors are typically smooth. It is of interest to characterize tumor branchiness (roughness) to differentiate invasive malignant breast cancer from noninvasive ones. In this study, we examined the shear modulus (G) to elastic modulus (E) ratio, G∕E, as a quantity to describe model tumor interfacial roughness using a piezoelectric cantilever capable of measuring both tissue elastic modulus and tissue shear modulus. The piezoelectric cantilever used had two lead zirconate titanate layers to facilitate all-electrical elastic (shear) modulus measurements using one single device. We constructed model tissues with tumors by embedding one-dimensional (1D) corrugated inclusions and three-dimensional (3D) spiky-ball inclusions made of modeling clay in gelatin. We showed that for smooth inclusions, G∕E was 0.3 regardless of the shear direction. In contrast, for a 1D corrugated rough inclusion G∕E was 0.3 only when the shear was parallel to corrugation and G∕E increased with an increasing angle between the shear direction and the corrugation. When the shear was perpendicular to corrugation, G∕E became >0.7. For 3D isotropic spiky-ball inclusions we showed that the G∕E depended on the degree of the roughness. Using the ratio s∕r of the spike length (s) to the overall inclusion radius (r) as a roughness parameter, we showed that for inclusions with s∕r larger than or equal to 0.28, the G∕E ratio over the inclusions was larger than 0.7 whereas for inclusions with s∕r less than 0.28, the G∕E decreased with decreasing s∕r to around 0.3 at s∕r=0. In addition, we showed that the depth limit of the G∕E measurement is twice the width of the probe area of the piezoelectric cantilever. PMID:20887005

  5. Detection and analysis of tumor fluorescence using a two-photon optical fiber probe.

    PubMed

    Thomas, Thommey P; Myaing, Mon Thiri; Ye, Jing Yong; Candido, Kimberly; Kotlyar, Alina; Beals, James; Cao, Peter; Keszler, Balazs; Patri, Anil K; Norris, Theodore B; Baker, James R

    2004-06-01

    The utility of a two-photon optical fiber fluorescence probe (TPOFF) for sensing and quantifying tumor fluorescent signals was tested in vivo. Xenograft tumors were developed in athymic mice using MCA207 cells expressing green fluorescent protein (GFP). The TPOFF probe was able to detect ex vivo fluorescence from excised tumors containing as little as 0.3% GFP-expressing cells. TPOFF results were similar to both flow-cytometric analysis of tumor cells after isolation and suspension, and fluorescence determined by microscope images of cryosectioned tumors. TPOFF was then used to measure GFP fluorescence from tumors in live mice. The fiber probe detected fluorescently-labeled Herceptin antibody targeted to HER2-expressing tumors in severe combined immunodeficient mice. Dendrimer nanoparticles targeted by folic acid and having 6-TAMRA as a fluorescent probe were also used to label KB cell tumors in vivo. The fiber probe documented a fourfold increase in tumor fluorescence in animals that received the targeted dendrimer. These results suggest TPOFF can be used as a minimally invasive system for identifying tumor markers and monitoring drug therapy.

  6. Computer-aided design of peptide near infrared fluorescent probe for tumor diagnosis

    NASA Astrophysics Data System (ADS)

    Zhang, Congying; Gu, Yueqing

    2014-09-01

    Integrin αvβ3 receptors are expressed on activated endothelial cells during neovascularization to maintain tumor growth, so they become hot research tagets in cancer diagnosis. Peptides possess several attractive features when compared to protein and small molecule, such as small size and high structural compatibility with target proteins. Efficient design of high-affinity peptide ligands to Integrin αvβ3 receptors has been an important problem. Designed peptides in silico provide a valuable and high-selectivity peptide, meanwhile decrease the time of drug screening. In this study, we design peptide which can bind with integrin αvβ3 via computer, and then synthesis near infrared fluorescent probe. The characterization of this near infrared fluorescent probe was detected by UV. To investigate the tumor cell targeting of this probe, it was labeled with visible fluorescent dye Rhodamine B (RhB) for microscopy. To evaluate the targeting capability of this near infrared fluorescent probe, mice bearing integrin αvβ3 positive tumor xenografts were used. In vitro cellular experiments indicated that this probe have a clear binding affinity to αvβ3-positive tumor cells. In vivo experiments confirmed the receptor binding specificity of this probe. The peptide of computational design can bind with integrin αvβ3. Combined peptide near-infrared fluorescent probe with imaging technology use for clinical and tumor diagnosis have a greater development in future.

  7. Near-infrared pH-activatable fluorescent probes for imaging primary and metastatic breast tumors.

    PubMed

    Lee, Hyeran; Akers, Walter; Bhushan, Kumar; Bloch, Sharon; Sudlow, Gail; Tang, Rui; Achilefu, Samuel

    2011-04-20

    Highly tumor selective near-infrared (NIR) pH-activatable probe was developed by conjugating pH-sensitive cyanine dye to a cyclic arginine-glycine-aspartic acid (cRGD) peptide targeting α(v)β(3) integrin (ABIR), a protein that is highly overexpressed in endothelial cells during tumor angiogenesis. The NIR pH-sensitive dye used to construct the probe exhibits high spectral sensitivity with pH changes. It has negligible fluorescence above pH 6 but becomes highly fluorescent below pH 5, with a pK(a) of 4.7. This probe is ideal for imaging acidic cell organelles such as tumor lysosomes or late endosomes. Cell microscopy data demonstrate that binding of the cRGD probe to ABIR facilitated the endocytosis-mediated lysosomal accumulation and subsequent fluorescence enhancement of the NIR pH-activatable dye in tumor cells (MDA-MB-435 and 4T1/luc). A similar fluorescence enhancement mechanism was observed in vivo, where the tumors were evident within 4 h post injection. Moreover, lung metastases were also visualized in an orthotopic tumor mouse model using this probe, which was further confirmed by histologic analysis. These results demonstrate the potential of using the new integrin-targeted pH-sensitive probe for the detection of primary and metastatic cancer.

  8. Fluorescence imaging of tumors with "smart" pH-activatable targeted probes.

    PubMed

    Asanuma, Daisuke; Kobayashi, Hisataka; Nagano, Tetsuo; Urano, Yasuteru

    2009-01-01

    One goal of molecular imaging is to establish a widely applicable technique for specific detection of tumors with minimal background originated from non-target tissues. In this study, a "smart" activatable strategy for specific tumor imaging is proposed in which pH-activatable targeted probes specifically detect tumors after binding to the target cell surface proteins, internalization, and eventual acidic pH activation within the acidic organelles. We successfully visualized submillimeter-sized tumors using this strategy in two different tumor mouse models. Since the design of pH-activatable targeted probes can be applied to any target molecules on the cell surface that are to be internalized after ligand binding, this imaging strategy can afford a general and powerful method to diagnose and monitor the target tumors.

  9. Systematic Construction and Calculation of Electronic Properties of Fullerene Series Related by Rotational Symmetry: From Fullerenes to Bicapped Nanotubes.

    PubMed

    Dias, Jerry Ray

    2016-06-01

    The results herein demonstrate that the methods of circumscribing and the facile calculation of Hückel molecular orbital (HMO) eigenvalues by mirror-plane fragmentation have a broad application in the construction of carbon cluster series and the systematic study of trends in their electronic properties. In comparing open-ended nanotubes and their isomeric elongated fullerenes (bicapped nanotubes), we show that the former are more aromatic but the latter are more conjugated and that progressive elongation increases aromaticity and conjugation in both. Recursion equations that will allow one to obtain the eigenvalues to all 5-endcapped nanotubes are given.

  10. Analysis of the Distribution of Magnetic Fluid inside Tumors by a Giant Magnetoresistance Probe

    PubMed Central

    Gooneratne, Chinthaka P.; Kurnicki, Adam; Yamada, Sotoshi; Mukhopadhyay, Subhas C.; Kosel, Jürgen

    2013-01-01

    Magnetic fluid hyperthermia (MFH) therapy uses the magnetic component of electromagnetic fields in the radiofrequency spectrum to couple energy to magnetic nanoparticles inside tumors. In MFH therapy, magnetic fluid is injected into tumors and an alternating current (AC) magnetic flux is applied to heat the magnetic fluid- filled tumor. If the temperature can be maintained at the therapeutic threshold of 42°C for 30 minutes or more, the tumor cells can be destroyed. Analyzing the distribution of the magnetic fluid injected into tumors prior to the heating step in MFH therapy is an essential criterion for homogenous heating of tumors, since a decision can then be taken on the strength and localization of the applied external AC magnetic flux density needed to destroy the tumor without affecting healthy cells. This paper proposes a methodology for analyzing the distribution of magnetic fluid in a tumor by a specifically designed giant magnetoresistance (GMR) probe prior to MFH heat treatment. Experimental results analyzing the distribution of magnetic fluid suggest that different magnetic fluid weight densities could be estimated inside a single tumor by the GMR probe. PMID:24312280

  11. Enhancement of Fluorescent Probe Penetration into Tumors In Vivo Using Unseeded Inertial Cavitation.

    PubMed

    Prieur, Fabrice; Pillon, Arnaud; Mestas, Jean-Louis; Cartron, Valérie; Cèbe, Patrick; Chansard, Nathalie; Lafond, Maxime; Lafon, Cyril

    2016-07-01

    Ultrasound-induced cavitation has found many applications in the field of cancer therapy. One of its beneficial effects is the enhancement of drug intake by tumor cells. Our group has developed a device that can create and control unseeded cavitation in tissue using ultrasound. We conducted experiments on tumor-bearing mice using our device to assess the impact of sonication on the penetration of fluorescent probes into tumor cells. We studied the influence of pressure level, timing of sonication and sonication duration on treatment efficiency. Our results indicate that fluorescent probes penetrate better into tumors exposed to ultrasound. The best results revealed an increase in penetration of 61% and were obtained when sonicating the tumor in presence of the probes with a peak negative pressure at focus of 19 MPa. At this pressure level, the treatment generated only minor skin damage. Treatments could be significantly accelerated as equivalent enhanced penetration of probes was achieved when multiplying the initial raster scan speed by a factor of four. PMID:27087691

  12. Docosahexaenoic acid conjugated near infrared flourescence probe for in vivo early tumor diagnosis

    NASA Astrophysics Data System (ADS)

    Li, Siwen; Cao, Jie; Qin, Jingyi; Zhang, Xin; Achilefu, Samuel; Qian, Zhiyu; Gu, Yueqing

    2013-02-01

    Docosahexaenoic acid(DHA) is an omega-3 C22 natural fatty acid with six cis double bonds and as a constituent of membranes used as a precursor for metabolic and biochemical path ways. In this manuscript,we describe the synthesis of near-infrared(NIR) flourescence ICG-Der-01 labeled DHA for in vitro and vivo tumor targeting.The structure of the probe was intensively characterized by UV and MS. The in vitro and vivo tumor targeting abilities of the DHA-based NIR probes were investigeted in MCF-7 cells and MCF-7 xenograft mice model differently by confocal microscopy and CCD camera. The cell cytotoxicity were tested in tumor cells MCF-7 .The results shows that the DHA-based NIR probes have high affinity with the tumor both in vitro and vivo.In addition ,we also found that the DHA-based NIR probes have the apparent cytotoxicity on MCF-7 cells .which demonstrated that DHA was conjugated with other antitumor drug could increase the abilities of antirumor efficacy .So DHA-ICG-Der-01 is a promising optical agent for diagnosis of tumors especially in their early stage.

  13. Bimolecular complementation affinity purification (BiCAP) reveals dimer-specific protein interactions for ERBB2 dimers.

    PubMed

    Croucher, David R; Iconomou, Mary; Hastings, Jordan F; Kennedy, Sean P; Han, Jeremy Z R; Shearer, Robert F; McKenna, Jessie; Wan, Adrian; Lau, Joseph; Aparicio, Samuel; Saunders, Darren N

    2016-01-01

    The dynamic assembly of multiprotein complexes is a central mechanism of many cell signaling pathways. This process is key to maintaining the spatiotemporal specificity required for an accurate, yet adaptive, response to rapidly changing cellular conditions. We describe a technique for the specific isolation and downstream proteomic characterization of any two interacting proteins, to the exclusion of their individual moieties and competing binding partners. We termed the approach bimolecular complementation affinity purification (BiCAP) because it combines the use of conformation-specific nanobodies with a protein-fragment complementation assay with affinity purification. Using BiCAP, we characterized the specific interactome of the epidermal growth factor receptor (EGFR) family member ERBB2 when in the form of a homodimer or when in the form of a heterodimer with either EGFR or ERBB3. We identified dimer-specific interaction patterns for key adaptor proteins and identified a number of previously unknown interacting partners. Functional analysis for one of these newly identified partners revealed a noncanonical mechanism of extracellular signal-regulated kinase (ERK) activation that is specific to the ERBB2:ERBB3 heterodimer and acts through the adaptor protein FAM59A in breast cancer cells. PMID:27405979

  14. Single-cell profiling approaches to probing tumor heterogeneity.

    PubMed

    Khoo, Bee Luan; Chaudhuri, Parthiv Kant; Ramalingam, Naveen; Tan, Daniel Shao Weng; Lim, Chwee Teck; Warkiani, Majid Ebrahimi

    2016-07-15

    Tumor heterogeneity is a major hindrance in cancer classification, diagnosis and treatment. Recent technological advances have begun to reveal the true extent of its heterogeneity. Single-cell analysis (SCA) is emerging as an important approach to detect variations in morphology, genetic or proteomic expression. In this review, we revisit the issue of inter- and intra-tumor heterogeneity, and list various modes of SCA techniques (cell-based, nucleic acid-based, protein-based, metabolite-based and lipid-based) presently used for cancer characterization. We further discuss the advantages of SCA over pooled cell analysis, as well as the limitations of conventional techniques. Emerging trends, such as high-throughput sequencing, are also mentioned as improved means for cancer profiling. Collectively, these applications have the potential for breakthroughs in cancer treatment. PMID:26789729

  15. Micro-CT molecular imaging of tumor angiogenesis using a magnetite nano-cluster probe.

    PubMed

    Liu, Ping; Li, Jing; Zhang, Chunfu; Xu, Lisa X

    2013-06-01

    Due to its high resolution, micro-CT is desirable for molecular imaging of tumor angiogenesis. However, the sensitivity of micro-CT to contrast agents is relatively low. Therefore, the purpose of this study is to develop high micro-CT sensitive molecular imaging probes for direct visualization and dynamic monitoring of tumor angiogenesis. To this end, Arg-Gly-Asp (RGD) peptides conjugated magnetite nano clusters (RGD-MNCs) were developed by assembling individual magnetite nano particles into clusters with amphiphilic (maleimide) methoxypoly(ethylene glycol)-b-poly(lactic acid) ((Mal)mPEG-PLA) copolymer and subsequently encoding RGD peptides onto the clusters for specific targeting alpha(v)beta3 integrin. The hydrodynamic size of RGD-MNCs was about 85 nm. To test its specificity, alpha(v)beta3 positive cells (H1299) were incubated with magnetite nano clusters (MNCs), RGD-MNCs or RGD-MNCs competition with free RGD peptides. Prussian Blue staining and inductively coupled plasma optical emission spectrometer (ICP-OES) measurements indicated that the cell uptake of RGD-MNCs was significantly more than that of MNCs, which could be inhibited by free RGD peptides. For detection of tumor angiogenesis, mice bearing H1299 tumors were injected intravenously with RGD-MNCs at the dose of 400 micro mol Fe/kg. Tumor angiogenic hot spots as well as individual angiogenic vessels could be clearly manifested by micro-CT imaging 12 h post injection, which was dynamically monitored with the extension of probe circulation time. Subsequent histological studies of tumor tissues verified that RGD-MNCs registered tumor angiogenic vessels. Our study demonstrated that RGD-MNC probes fabricated in this study could be used to effectively target alpha(v)beta3 integrin. Using high resolution micro-CT in combination with the probes, tumor angiogenesis could be studied dynamically.

  16. Single cell molecular recognition of migrating and invading tumor cells using a targeted fluorescent probe to receptor PTPmu.

    PubMed

    Burden-Gulley, Susan M; Qutaish, Mohammed Q; Sullivant, Kristin E; Tan, Mingqian; Craig, Sonya E L; Basilion, James P; Lu, Zheng-Rong; Wilson, David L; Brady-Kalnay, Susann M

    2013-04-01

    Detection of an extracellular cleaved fragment of a cell-cell adhesion molecule represents a new paradigm in molecular recognition and imaging of tumors. We previously demonstrated that probes that recognize the cleaved extracellular domain of receptor protein tyrosine phosphatase mu (PTPmu) label human glioblastoma brain tumor sections and the main tumor mass of intracranial xenograft gliomas. In this article, we examine whether one of these probes, SBK2, can label dispersed glioma cells that are no longer connected to the main tumor mass. Live mice with highly dispersive glioma tumors were injected intravenously with the fluorescent PTPmu probe to test the ability of the probe to label the dispersive glioma cells in vivo. Analysis was performed using a unique three-dimensional (3D) cryo-imaging technique to reveal highly migratory and invasive glioma cell dispersal within the brain and the extent of colabeling by the PTPmu probe. The PTPmu probe labeled the main tumor site and dispersed cells up to 3.5 mm away. The cryo-images of tumors labeled with the PTPmu probe provide a novel, high-resolution view of molecular tumor recognition, with excellent 3D detail regarding the pathways of tumor cell migration. Our data demonstrate that the PTPmu probe recognizes distant tumor cells even in parts of the brain where the blood-brain barrier is likely intact. The PTPmu probe has potential translational significance for recognizing tumor cells to facilitate molecular imaging, a more complete tumor resection and to serve as a molecular targeting agent to deliver chemotherapeutics to the main tumor mass and distant dispersive tumor cells.

  17. Single cell molecular recognition of migrating and invading tumor cells using a targeted fluorescent probe to receptor PTPmu.

    PubMed

    Burden-Gulley, Susan M; Qutaish, Mohammed Q; Sullivant, Kristin E; Tan, Mingqian; Craig, Sonya E L; Basilion, James P; Lu, Zheng-Rong; Wilson, David L; Brady-Kalnay, Susann M

    2013-04-01

    Detection of an extracellular cleaved fragment of a cell-cell adhesion molecule represents a new paradigm in molecular recognition and imaging of tumors. We previously demonstrated that probes that recognize the cleaved extracellular domain of receptor protein tyrosine phosphatase mu (PTPmu) label human glioblastoma brain tumor sections and the main tumor mass of intracranial xenograft gliomas. In this article, we examine whether one of these probes, SBK2, can label dispersed glioma cells that are no longer connected to the main tumor mass. Live mice with highly dispersive glioma tumors were injected intravenously with the fluorescent PTPmu probe to test the ability of the probe to label the dispersive glioma cells in vivo. Analysis was performed using a unique three-dimensional (3D) cryo-imaging technique to reveal highly migratory and invasive glioma cell dispersal within the brain and the extent of colabeling by the PTPmu probe. The PTPmu probe labeled the main tumor site and dispersed cells up to 3.5 mm away. The cryo-images of tumors labeled with the PTPmu probe provide a novel, high-resolution view of molecular tumor recognition, with excellent 3D detail regarding the pathways of tumor cell migration. Our data demonstrate that the PTPmu probe recognizes distant tumor cells even in parts of the brain where the blood-brain barrier is likely intact. The PTPmu probe has potential translational significance for recognizing tumor cells to facilitate molecular imaging, a more complete tumor resection and to serve as a molecular targeting agent to deliver chemotherapeutics to the main tumor mass and distant dispersive tumor cells. PMID:22987116

  18. A bispecific peptide based near-infrared probe for in vivo tumor diagnosis

    NASA Astrophysics Data System (ADS)

    Ding, Li; Chen, Wei R.; Gu, Yueqing

    2013-02-01

    The epidermal growth factor receptor EGFR and HER2 are members of recepeter tyrosine kinase family. Overexpression of EGFR and HER2 has been observed in a variety of human tumors, making these receptors promising targets for tumor diagnosis. An affibody targeting HER2 and a nanobody targeting EGFR were reported before. In this Manuscript, we described an bispecific peptide combined with an affibody and a nanonbody through a linker―(G4S)3 . And the bispecific peptide was labeled with near-infrared (NIR) fluorochrome ICG-Der-02 for in vivo tumor EGFR and HER2 targeting. Afterwards, the EGFR and HER2 specificity of the fluorescent probe was tested in vitro for receptor binding assay and fluorescence microscopy and in vivo for subcutaneous MDA-MB-231 tumor targeting. The results indicated that the bispecific peptide had a high affinity to EGFR and HER2. Besides, in vitro and in vivo tumor targeting experiment indicated that the ICG-Der-02-( bispecific peptide) showed excellent tumor activity accumulation. Noninvasive NIR fluorescence imaging is able to detect tumor EGFR and HER2 expression based upon the highly potent bispecific peptide probe.

  19. A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy.

    PubMed

    Liu, Yang; Ashton, Jeffrey R; Moding, Everett J; Yuan, Hsiangkuo; Register, Janna K; Fales, Andrew M; Choi, Jaeyeon; Whitley, Melodi J; Zhao, Xiaoguang; Qi, Yi; Ma, Yan; Vaidyanathan, Ganesan; Zalutsky, Michael R; Kirsch, David G; Badea, Cristian T; Vo-Dinh, Tuan

    2015-01-01

    Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy.

  20. A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy

    PubMed Central

    Liu, Yang; Ashton, Jeffrey R.; Moding, Everett J.; Yuan, Hsiangkuo; Register, Janna K.; Fales, Andrew M.; Choi, Jaeyeon; Whitley, Melodi J.; Zhao, Xiaoguang; Qi, Yi; Ma, Yan; Vaidyanathan, Ganesan; Zalutsky, Michael R.; Kirsch, David G.; Badea, Cristian T.; Vo-Dinh, Tuan

    2015-01-01

    Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy. PMID:26155311

  1. A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy.

    PubMed

    Liu, Yang; Ashton, Jeffrey R; Moding, Everett J; Yuan, Hsiangkuo; Register, Janna K; Fales, Andrew M; Choi, Jaeyeon; Whitley, Melodi J; Zhao, Xiaoguang; Qi, Yi; Ma, Yan; Vaidyanathan, Ganesan; Zalutsky, Michael R; Kirsch, David G; Badea, Cristian T; Vo-Dinh, Tuan

    2015-01-01

    Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy. PMID:26155311

  2. MUC1 aptamer based near infrared fluorescence probes for tumor diagnosis

    NASA Astrophysics Data System (ADS)

    Zhao, Juan; Ma, Yuxiang; Cui, Sisi; Cao, Jie; Achilefu, Samuel; Gu, Yueqing

    2013-02-01

    Mucin 1 (MUC1) is a cell surface mucin broadly expressed in mucosal tissues. The aberrant expression of MUC1 under-glycosylated forms has been reported in various carcinomas of the epithelium, such as breast, pancreatic and ovarian cancers. Using the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) methodology, aptamers previously selected against MUC1 glycoprotein with high affinities and specificities. In this study, we developed two targeted near-infrared fluorescent probes for tumor in-vivo diagnostics using a MUC1 aptamer(APT) as targeted ligand and near-infrared fluorescent dye (ICG-Der-02) as labelling. MUC1 aptamer conjugated ICG-Der-02 (APT-ICG-Der-02) displayed a great selectivity to MUC1 positive cell line MCF7 and MCF7 xenograft-bearing nude mice. To improve the high targeting of the probe to the tumor cells, PEG, with high biocompatibility, non immunogenicity and long circulation, was conjugated to the probe .The new probe (APT-PEG-ICG-Der-02) showed better tumour uptake and clearance, and also displayed a great selectivity to MCF7 tumor-bearing nude mice. Data obtained demonstrate a high potential of the targeted near-infrared fluorescent probes in cancer early diagnosis.

  3. Endohedral nickel, palladium, and platinum atoms in 10-vertex germanium clusters: competition between bicapped square antiprismatic and pentagonal prismatic structures.

    PubMed

    King, R B; Silaghi-Dumitrescu, I; Uţa, M M

    2009-01-22

    Density functional theory predicts significant differences in the preferred structures of endohedral M@Ge10z (M = Ni, Pd, Pt; z = 0, 2-, 4-) clusters upon a change of the central metal atom in otherwise isoelectronic systems. For the neutral clusters M@Ge10 the global minima are singlet bicapped square antiprisms. However, triplet regular pentagonal prismatic structures become increasingly energetically competitive in the series Ni --> Pd -> Pt. The pentagonal prismatic dianions M@Ge10(2-) (M = Ni, Pd, Pt) appear to have closed shell structures and are the global minima for palladium and platinum. However, the global minimum for Ni@Ge102- is the capped square antiprism suggested by the Wade-Mingos rules. A number of singlet low-energy unsymmetrical structures are found for the tetraanions M@Ge10(4-). However, for the palladium and platinum tetraanions triplet pentagonal prismatic structures are energetically competitive with the unsymmetrical structures.

  4. Cellular Activation of the Self-Quenched Fluorescent Reporter Probe in Tumor Microenvironment

    PubMed Central

    Bogdanov, Alexei A; Lin, Charles P; Simonova, Maria; Matuszewski, Lars; Weissleder, Ralph

    2002-01-01

    Abstract The effect of intralysosomal proteolysis of near-infrared fluorescent (NIRF) self-quenched macromolecular probe (PGC-Cy5.5) has been previously reported and used for tumor imaging. Here we demonstrate that proteolysis can be detected noninvasively in vivo at the cellular level. A codetection of GFP fluorescence (using two-photon excitation) and NIRF was performed in tumor-bearing animals injected with PGC-Cy5.5. In vivo microscopy of tumor cells in subdermal tissue layers (up to 160 µm) showed a strong Cy5.5 dequenching effect in GFP-negative cells. This observation was corroborated by flow cytometry, sorting, and reverse transcription polymerase chain reaction analysis of tumor-isolated cells. Both GFP-positive (81% total) and GFP-negative (19% total) populations contained Cy5.5-positive cells. The GFP-negative cells were confirmed to be host mouse cells by the absence of rat cathepsin mRNA signal. The subfraction of GFP-negative cells (2.5–3.0%) had seven times higher NIRF intensity than the majority of GFP-positive or GFP-negative cells (372 and 55 AU, respectively). Highly NIRF-positive, FP-negative cells were CD45- and MAC3-positive. Our results indicate that: 1) intracellular proteolysis can be imaged in vivo at the cellular level using cathepsin-sensitive probes; 2) tumor-recruited cells of hematopoetic origin participate most actively in uptake and degradation of long-circulating macromolecular probes. PMID:11988842

  5. Fluorescence in vivo imaging of live tumor cells with pH-activatable targeted probes via receptor-mediated endocytosis

    NASA Astrophysics Data System (ADS)

    Asanuma, Daisuke; Urano, Yasuteru; Nagano, Tetsuo; Hama, Yukihiro; Koyama, Yoshinori; Kobayashi, Hisataka

    2009-02-01

    One goal of molecular imaging is to establish a widely applicable technique for specific detection of tumors with minimal background. Here, we achieve specific in vivo tumor visualization with a newly-designed "activatable" targeted fluorescence probe. This agent is activated after cellular internalization by sensing the pH change in the lysosome. Novel acidic pH-activatable probes based on the BODIPY fluorophore were synthesized, and then conjugated to a cancer-targeting monoclonal antibody, Trastuzumab, or galactosyl serum albumin (GSA). As proof of concept, ex and in vivo imaging of two different tumor mouse models was performed: HER2-overexpressed lung metastasis tumor with Trastuzumab-pH probe conjugates and lectin-overexpressed i.p. disseminated tumor with GSA-pH probe conjugates. These pH-activatable targeted probes were highly specific for tumors with minimal background signal. Because the acidic pH in lysosomes is maintained by the energy-consuming proton pump, only viable cancer cells were successfully visualized. Furthermore, this strategy was also applied to fluorescence endoscopy in tumor mouse models, resulting in specific visualization of tumors as small as submillimeter in size that could hardly detected by naked eyes because of their poor contrast against normal tissues. The design concept can be widely adapted to cancer-specific cell-surface-targeting molecules that result in cellular internalization.

  6. Activatable Water-Soluble Probes Enhance Tumor Imaging by Responding to Dysregulated pH and Exhibiting High Tumor-to-Liver Fluorescence Emission Contrast.

    PubMed

    Xiong, Hu; Kos, Petra; Yan, Yunfeng; Zhou, Kejin; Miller, Jason B; Elkassih, Sussana; Siegwart, Daniel J

    2016-07-20

    Dysregulated pH has been recognized as a universal tumor microenvironment signature that can delineate tumors from normal tissues. Existing fluorescent probes that activate in response to pH are hindered by either fast clearance (in the case of small molecules) or high liver background emission (in the case of large particles). There remains a need to design water-soluble, long circulating, pH-responsive nanoprobes with high tumor-to-liver contrast. Herein, we report a modular chemical strategy to create acidic pH-sensitive and water-soluble fluorescent probes for high in vivo tumor detection and minimal liver activation. A combination of a modified Knoevenagel reaction and PEGylation yielded a series of NIR BODIPY fluorophores with tunable pKas, high quantum yield, and optimal orbital energies to enable photoinduced electron transfer (PeT) activation in response to pH. After intravenous administration, Probe 5c localized to tumors and provided excellent tumor-to-liver contrast (apparent T/L = 3) because it minimally activates in the liver. This phenomenon was further confirmed by direct ex vivo imaging experiments on harvested organs. Because no targeting ligands were required, we believe that this report introduces a versatile strategy to directly synthesize soluble probes with broad potential utility including fluorescence-based image-guided surgery, cancer diagnosis, and theranostic nanomedicine.

  7. Cysteine cathepsins: their role in tumor progression and recent trends in the development of imaging probes

    PubMed Central

    Löser, Reik; Pietzsch, Jens

    2015-01-01

    Papain-like cysteine proteases bear an enormous potential as drug discovery targets for both infectious and systemic human diseases. The considerable progress in this field over the last two decades has also raised interest in the visualization of these enzymes in their native context, especially with regard to tumor imaging. After a short introduction to structure and general functions of human cysteine cathepsins, we highlight their importance for drug discovery and development and provide a critical update on the current state of knowledge toward their involvement in tumor progression, with a special emphasis on their role in therapy response. In accordance with a radiopharmaceutical point of view, the main focus of this review article will be the discussion of recently developed fluorescence and radiotracer-based imaging agents together with related molecular probes. PMID:26157794

  8. Cysteine cathepsins: their role in tumor progression and recent trends in the development of imaging probes

    NASA Astrophysics Data System (ADS)

    Löser, Reik; Pietzsch, Jens

    2015-06-01

    Papain-like cysteine proteases bear an enormous potential as drug discovery targets for both infectious and systemic human diseases. The considerable progress in this field over the last two decades has also raised interest in the visualization of these enzymes in their native context, especially with regard to tumor imaging. After a short introduction to structure and general functions of human cysteine cathepsins, we highlight their importance for drug discovery and development and provide a critical update on the current state of knowledge towards their involvement in tumor progression, with a special emphasis on their role in therapy response. In accordance with a radiopharmaceutical point of view, the main focus of this review article will be the discussion of recently developed fluorescence and radiotracer-based imaging agents together with related molecular probes.

  9. Efficient Two-Photon Fluorescent Probe for Nitroreductase Detection and Hypoxia Imaging in Tumor Cells and Tissues.

    PubMed

    Zhang, Jing; Liu, Hong-Wen; Hu, Xiao-Xiao; Li, Jin; Liang, Li-Hui; Zhang, Xiao-Bing; Tan, Weihong

    2015-12-01

    Hypoxia plays an important role in tumor progression, and the development of efficient methods for monitoring hypoxic degree in living systems is of great biomedical importance. In the solid tumors, the nitroreductase level is directly corresponded with the hypoxic status. Many one-photon excited fluorescent probes have been developed for hypoxia imaging in tumor cells via the detection of nitroreductase level. However, two-photon excited probes are more suitable for bioimaging. In this work, a two-photon probe 1 for nitroreductase detection and hypoxic status monitoring in living tumor cells and tissues was reported for the first time. The detection is based on the fact that the nitro-group of probe 1 could be selectively reduced to an amino-group by nitroreductase in the presence of reduced NADH, following by a 1,6-rearrangement-elimination to release the fluorophore, resulting in the enhancement of fluorescence. The probe exhibited both one-photon and two-photon excited remarkable fluorescence enhancement (∼70-fold) for nitroreductase, which afforded a high sensitivity for nitroreductase, with a detection limit of 20 ng/mL observed. Moreover, the applications of the probe for fluorescent bioimaging of hypoxia in living cells and two-photon bioimaging in tissues were carried out, with tissue-imaging depths of 70-160 μm observed, which demonstrates its practical application in complex biosystems.

  10. Probing matrix and tumor mechanics with in situ calibrated optical trap based active microrheology

    NASA Astrophysics Data System (ADS)

    Staunton, Jack Rory; Vieira, Wilfred; Tanner, Kandice; Tissue Morphodynamics Unit Team

    Aberrant extracellular matrix deposition and vascularization, concomitant with proliferation and phenotypic changes undergone by cancer cells, alter mechanical properties in the tumor microenvironment during cancer progression. Tumor mechanics conversely influence progression, and the identification of physical biomarkers promise improved diagnostic and prognostic power. Optical trap based active microrheology enables measurement of forces up to 0.5 mm within a sample, allowing interrogation of in vitro biomaterials, ex vivo tissue sections, and small organisms in vivo. We fabricated collagen I hydrogels exhibiting distinct structural properties by tuning polymerization temperature Tp, and measured their shear storage and loss moduli at frequencies 1-15k Hz at multiple amplitudes. Lower Tp gels, with larger pore size but thicker, longer fibers, were stiffer than higher Tp gels; decreasing strain increased loss moduli and decreased storage moduli at low frequencies. We subcutanously injected probes with metastatic murine melanoma cells into mice. The excised tumors displayed storage and loss moduli 40 Pa and 10 Pa at 1 Hz, increasing to 500 Pa and 1 kPa at 15 kHz, respectively.

  11. In vivo proton-electron double-resonance imaging of extracellular tumor pH using an advanced nitroxide probe.

    PubMed

    Samouilov, Alexandre; Efimova, Olga V; Bobko, Andrey A; Sun, Ziqi; Petryakov, Sergey; Eubank, Timothy D; Trofimov, Dmitrii G; Kirilyuk, Igor A; Grigor'ev, Igor A; Takahashi, Wataru; Zweier, Jay L; Khramtsov, Valery V

    2014-01-21

    A variable radio frequency proton-electron double-resonance imaging (VRF PEDRI) approach for pH mapping of aqueous samples has been recently developed (Efimova et al. J. Magn. Reson. 2011, 209, 227-232). A pH map is extracted from two PEDRI acquisitions performed at electron paramagnetic resonance (EPR) frequencies of protonated and unprotonated forms of a pH-sensitive probe. To translate VRF PEDRI to an in vivo setting, an advanced pH probe was synthesized. Probe deuteration resulted in a narrow spectral line of 1.2 G compared to a nondeuterated analogue line width of 2.1 G allowing for an increase of Overhauser enhancements and reduction in rf power deposition. Binding of the probe to the cell-impermeable tripeptide, glutathione (GSH), allows for targeting to extracellular tissue space for monitoring extracellular tumor acidosis, a prognostic factor in tumor pathophysiology. The probe demonstrated pH sensitivity in the 5.8-7.8 range, optimum for measurement of acidic extracellular tumor pH (pH(e)). In vivo VRF PEDRI was performed on Met-1 tumor-bearing mice. Compared to normal mammary glands with a neutral mean pH(e) (7.1 ± 0.1), we observed broader pH distribution with acidic mean pH(e) (6.8 ± 0.1) in tumor tissue. In summary, VRF PEDRI in combination with a newly developed pH probe provides an analytical approach for spatially resolved noninvasive pHe monitoring, in vivo.

  12. In vivo proton-electron double-resonance imaging of extracellular tumor pH using an advanced nitroxide probe.

    PubMed

    Samouilov, Alexandre; Efimova, Olga V; Bobko, Andrey A; Sun, Ziqi; Petryakov, Sergey; Eubank, Timothy D; Trofimov, Dmitrii G; Kirilyuk, Igor A; Grigor'ev, Igor A; Takahashi, Wataru; Zweier, Jay L; Khramtsov, Valery V

    2014-01-21

    A variable radio frequency proton-electron double-resonance imaging (VRF PEDRI) approach for pH mapping of aqueous samples has been recently developed (Efimova et al. J. Magn. Reson. 2011, 209, 227-232). A pH map is extracted from two PEDRI acquisitions performed at electron paramagnetic resonance (EPR) frequencies of protonated and unprotonated forms of a pH-sensitive probe. To translate VRF PEDRI to an in vivo setting, an advanced pH probe was synthesized. Probe deuteration resulted in a narrow spectral line of 1.2 G compared to a nondeuterated analogue line width of 2.1 G allowing for an increase of Overhauser enhancements and reduction in rf power deposition. Binding of the probe to the cell-impermeable tripeptide, glutathione (GSH), allows for targeting to extracellular tissue space for monitoring extracellular tumor acidosis, a prognostic factor in tumor pathophysiology. The probe demonstrated pH sensitivity in the 5.8-7.8 range, optimum for measurement of acidic extracellular tumor pH (pH(e)). In vivo VRF PEDRI was performed on Met-1 tumor-bearing mice. Compared to normal mammary glands with a neutral mean pH(e) (7.1 ± 0.1), we observed broader pH distribution with acidic mean pH(e) (6.8 ± 0.1) in tumor tissue. In summary, VRF PEDRI in combination with a newly developed pH probe provides an analytical approach for spatially resolved noninvasive pHe monitoring, in vivo. PMID:24372284

  13. Phosphorescent light-emitting iridium complexes serve as a hypoxia-sensing probe for tumor imaging in living animals

    NASA Astrophysics Data System (ADS)

    Takeuchi, Toshiyuki; Zhang, Shaojuan; Negishi, Kazuya; Yoshihara, Toshitada; Hosaka, Masahiro; Tobita, Seiji

    2010-02-01

    Iridium complex, a promising organic light-emitting diode material for next generation television and computer displays, emits phosphorescence. Phosphorescence is quenched by oxygen. We used this oxygen-quenching feature for imaging tumor hypoxia. Red light-emitting iridium complex Ir(btp)2(acac) (BTP) presented hypoxia-dependent light emission in culture cell lines, whose intensity was in parallel with hypoxia-inducible factor (HIF)-1 expression. BTP was further applied to imaging five nude mouse-transplanted tumors. All tumors presented a bright BTP-emitting image as early as 5 min after the injection. The BTP-dependent tumor image peaked at 1 to 2 h after the injection, and was then removed from tumors within 24 h. The minimal BTP image recognition size was at least 2 mm in diameter. By morphological examination and phosphorescence lifetime measurement, BTP is presumed to localize to the tumor cells, not to stay in the tumor microvessels by binding to albumin. The primary problem on suse of luminescent probe for tumor imaging is its weak penetrance to deep tissues from the skin surface. Since BTP is easily modifiable, we made BTP analogues with a longer excitation/emission wavelength to improve the tissue penetrance. One of them, BTPHSA, displayed 560/720 wavelength, and depicted its clear imaging from tumors transplanted over 6-7 mm deep from the skin surface. We suggest that BTP analogues have a vast potential for imaging hypoxic lesions such as tumor tissues.

  14. Azo-Based Iridium(III) Complexes as Multicolor Phosphorescent Probes to Detect Hypoxia in 3D Multicellular Tumor Spheroids

    PubMed Central

    Sun, Lingli; Li, Guanying; Chen, Xiang; Chen, Yu; Jin, Chengzhi; Ji, Liangnian; Chao, Hui

    2015-01-01

    Hypoxia is an important characteristic of malignant solid tumors and is considered as a possible causative factor for serious resistance to chemo- and radiotherapy. The exploration of novel fluorescent probes capable of detecting hypoxia in solid tumors will aid tumor diagnosis and treatment. In this study, we reported the design and synthesis of a series of “off-on” phosphorescence probes for hypoxia detection in adherent and three-dimensional multicellular spheroid models. All of the iridium(III) complexes incorporate an azo group as an azo-reductase reactive moiety to detect hypoxia. Reduction of non-phosphorescent probes Ir1-Ir8 by reductases under hypoxic conditions resulted in the generation of highly phosphorescent corresponding amines for detection of hypoxic regions. Moreover, these probes can penetrate into 3D multicellular spheroids over 100 μm and image the hypoxic regions. Most importantly, these probes display a high selectivity for the detection of hypoxia in 2D cells and 3D multicellular spheroids. PMID:26423609

  15. (99m)Tc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study.

    PubMed

    Essa, B M; Sakr, T M; Khedr, Mohammed A; El-Essawy, F A; El-Mohty, A A

    2015-08-30

    Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their high binding affinity to the LPO enzyme. A computational study was used to select top-ranked LPO inhibitor (alone and in complex with (99m)Tc) with high in silico affinity. The novel prepared (99m)Tc-amitrole complex demonstrated both in silico and in vivo high affinity toward solid tumors.(99m)Tc-amitrole was radio-synthesized with a high radiochemical yield (89.7±3.25). It showed in vitro stability for up to 6h. Its preclinical evaluation in solid tumor-bearing mice showed high retention and biological accumulation in solid tumor cells with a high Target/Non-Target (T/NT) ratio equal to 4.9 at 60min post-injection. The data described previously could recommend (99m)Tc-amitrole as potential targeting scintigraphic probe for solid tumor imaging.

  16. (99m)Tc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study.

    PubMed

    Essa, B M; Sakr, T M; Khedr, Mohammed A; El-Essawy, F A; El-Mohty, A A

    2015-08-30

    Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their high binding affinity to the LPO enzyme. A computational study was used to select top-ranked LPO inhibitor (alone and in complex with (99m)Tc) with high in silico affinity. The novel prepared (99m)Tc-amitrole complex demonstrated both in silico and in vivo high affinity toward solid tumors.(99m)Tc-amitrole was radio-synthesized with a high radiochemical yield (89.7±3.25). It showed in vitro stability for up to 6h. Its preclinical evaluation in solid tumor-bearing mice showed high retention and biological accumulation in solid tumor cells with a high Target/Non-Target (T/NT) ratio equal to 4.9 at 60min post-injection. The data described previously could recommend (99m)Tc-amitrole as potential targeting scintigraphic probe for solid tumor imaging. PMID:25956074

  17. Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor

    PubMed Central

    Parashurama, Natesh; O’Sullivan, Thomas D.; De La Zerda, Adam; El Kalassi, Pascale; Cho, Seongjae; Liu, Hongguang; Teed, Robert; Levy, Hart; Rosenberg, Jarrett; Cheng, Zhen; Levi, Ofer; Harris, James S.

    2012-01-01

    Abstract. Molecular optical imaging is a widespread technique for interrogating molecular events in living subjects. However, current approaches preclude long-term, continuous measurements in awake, mobile subjects, a strategy crucial in several medical conditions. Consequently, we designed a novel, lightweight miniature biosensor for in vivo continuous optical sensing. The biosensor contains an enclosed vertical-cavity surface-emitting semiconductor laser and an adjacent pair of near-infrared optically filtered detectors. We employed two sensors (dual sensing) to simultaneously interrogate normal and diseased tumor sites. Having established the sensors are precise with phantom and in vivo studies, we performed dual, continuous sensing in tumor (human glioblastoma cells) bearing mice using the targeted molecular probe cRGD-Cy5.5, which targets αVβ3 cell surface integrins in both tumor neovasculature and tumor. The sensors capture the dynamic time-activity curve of the targeted molecular probe. The average tumor to background ratio after signal calibration for cRGD-Cy5.5 injection is approximately 2.43±0.95 at 1 h and 3.64±1.38 at 2 h (N=5 mice), consistent with data obtained with a cooled charge coupled device camera. We conclude that our novel, portable, precise biosensor can be used to evaluate both kinetics and steady state levels of molecular probes in various disease applications. PMID:23123976

  18. In vivo intra-operative breast tumor margin detection using a portable OCT system with a handheld surgical imaging probe

    NASA Astrophysics Data System (ADS)

    Erickson-Bhatt, Sarah J.; Nolan, Ryan; Shemonski, Nathan D.; Adie, Steven G.; Putney, Jeffrey; Darga, Donald; McCormick, Daniel T.; Cittadine, Andrew; Marjanovic, Marina; Chaney, Eric J.; Monroy, Guillermo L.; South, Fredrick; Carney, P. Scott; Cradock, Kimberly A.; Liu, Z. George; Ray, Partha S.; Boppart, Stephen A.

    2014-02-01

    Breast-conserving surgery is a frequent option for women with stage I and II breast cancer, and with radiation treatment, can be as effective as a mastectomy. However, adequate margin detection remains a challenge, and too often additional surgeries are required. Optical coherence tomography (OCT) provides a potential method for real-time, high-resolution imaging of breast tissue during surgery. Intra-operative OCT imaging of excised breast tissues has been previously demonstrated by several groups. In this study, a novel handheld surgical probe-based OCT system is introduced, which was used by the surgeon to image in vivo, within the tumor cavity, and immediately following tumor removal in order to detect the presence of any remaining cancer. Following resection, study investigators imaged the excised tissue with the same probe for comparison. We present OCT images obtained from over 15 patients during lumpectomy and mastectomy surgeries. Images were compared to post-operative histopathology for diagnosis. OCT images with micron scale resolution show areas of heterogeneity and disorganized features indicative of malignancy, compared to more uniform regions of normal tissue. Video-rate acquisition shows the inside of the tumor cavity as the surgeon sweeps the probe along the walls of the surgical cavity. This demonstrates the potential of OCT for real-time assessment of surgical tumor margins and for reducing the unacceptably high re-operation rate for breast cancer patients.

  19. SU-E-I-81: Targeting of HER2-Expressing Tumors with Dual PET-MR Imaging Probes

    SciTech Connect

    Xu, P; Peng, Y; Sun, M; Yang, X

    2015-06-15

    Purpose: The detection of human epidermal growth factor receptor type 2 (HER2) expression in malignant tumors provides important information influencing patient management. Radionuclide in vivo imaging of HER2 may permit the detection of HER2 in both primary tumors and metastases by a single noninvasive procedure. Trastuzumab, effective in about 15 % of women with breast cancer, downregulates signalling through the Akt/PI3K and MAPK pathways.These pathways modulate metabolism which can be monitored by positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: The relationship between response of HER2 overexpressing tumours and changes in imaging PET or SPECT and MRI will be examined by a integrated bimodal imaging probe.Small (7 kDa) high-affinity anti-HER2 Affibody molecules and KCCYSL targeting peptide may be suitable tracers for visualization of HER2-expressing tumors. Peptide-conjugated iron oxide nanoparticles (Fe3O4 NPs) as MRI imaging and CB-TE2A as PET imaging are integrated into a single synthetic molecule in the HER2 positive cancer. Results: One of targeted contrast bimodal imaging probe agents was synthesized and evaluated to target HER2-expressing tumors in a HER2 positive rat model. We will report the newest results regarding the development of bimodal imaging probes. Conclusion: The preliminary results of the bimodal imaging probe presents high correlation of MRI signal and PET imaging intensity in vivo. This unique feature can hardly be obtained by single model contrast agents. It is envisioned that this bimodal agents can hold great potential for accurate detection of HER2-expressing tumors which are critical for clinical management of the disease.

  20. Development of a spatially offset Raman spectroscopy probe for breast tumor surgical margin evaluation

    PubMed Central

    Keller, Matthew D.; Vargis, Elizabeth; de Matos Granja, Nara; Wilson, Robert H.; Mycek, Mary-Ann; Kelley, Mark C.; Mahadevan-Jansen, Anita

    2011-01-01

    The risk of local recurrence for breast cancers is strongly correlated with the presence of a tumor within 1 to 2 mm of the surgical margin on the excised specimen. Previous experimental and theoretical results suggest that spatially offset Raman spectroscopy (SORS) holds much promise for intraoperative margin analysis. Based on simulation predictions for signal-to-noise ratio differences among varying spatial offsets, a SORS probe with multiple source-detector offsets was designed and tested. It was then employed to acquire spectra from 35 frozen–thawed breast tissue samples in vitro. Spectra from each detector ring were averaged to create a composite spectrum with biochemical information covering the entire range from the tissue surface to ∼2 mm below the surface, and a probabilistic classification scheme was used to classify these composite spectra as “negative” or “positive” margins. This discrimination was performed with 95% sensitivity and 100% specificity, or with 100% positive predictive value and 94% negative predictive value. PMID:21806286

  1. Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

    PubMed Central

    DaGama Gomes, Erica M; Riolo, Matthew; Patel, Hardik J; Alonso-Sabadell, Raul; Zatorska, Danuta; Patel, Maulik R; Kishinevsky, Sarah

    2013-01-01

    Summary The attachment of biotin to a small molecule provides a powerful tool in biology. Here, we present a systematic approach to identify biotinylated analogues of the Hsp90 inhibitor PU-H71 that are capable of permeating cell membranes so as to enable the investigation of Hsp90 complexes in live cells. The identified derivative 2g can isolate Hsp90 through affinity purification and, as we show, represents a unique and useful tool to probe tumor Hsp90 biology in live cells by affinity capture, flow cytometry and confocal microscopy. To our knowledge, 2g is the only reported biotinylated Hsp90 probe to have such combined characteristics. PMID:23616796

  2. Photoacoustic imaging of small organic molecule-based photoacoustic probe in subcutaneous tumor using P(VDF-TrFE) acoustic sensor

    NASA Astrophysics Data System (ADS)

    Hirasawa, Takeshi; Okawa, Shinpei; Kamiya, Mako; Urano, Yasuteru; Ishihara, Miya

    2015-03-01

    The P(VDF-TrFE) sensor which had uniform sensitivity in a frequency range of 2.9 - 19.6 MHz was developed for multispectral photoacoustic imaging (MS-PAI). A small organic molecule-based PA probe synthesized by our group had the absorption maximum at 530 nm and was used as a contrast agent. The PA probe was designed to have low quantum yield. Therefore, the PA probe efficiently converted absorbed optical energies to PA signals. The probe was injected in subcutaneous tumor of mice. Then, the subcutaneous tumor was imaged in vivo by using P(VDF-TrFE) sensor. MS-PAI successfully discriminated the probe signals from background signals produced from endogenous optical absorbers such as hemoglobin. The probe detectability of the P(VDF-TrFE) sensor was evaluated and then compared with that of lead zirconium titanate (PZT) sensors. The P(VDF-TrFE) sensor imaged the tumor more clearly than the PZT sensor with central frequency of 20 MHz, especially when the probe was accumulated in the tumor with low concentration. That was because the low-concentrated probe generated PA signals with low frequency. MS-PAI using P(VDF-TrFE) sensor which can detect PA signals with wide range of frequency is able to image various distribution of the probe and is superior to that using PZT sensor which detects PA signals with narrow frequency range.

  3. Multi-parametric imaging of tumor spheroids with ultra-bright and tunable nanoparticle O2 probes

    NASA Astrophysics Data System (ADS)

    Dmitriev, Ruslan I.; Borisov, Sergey M.; Jenkins, James; Papkovsky, Dmitri B.

    2015-03-01

    Multi-modal probes allow for flexible choice of imaging equipment when performing quenched-phosphorescence O2 measurements: one- or two-photon, PLIM or intensity-based ratiometric read-outs. Spectral and temporal (e.g. FLIMPLIM) discrimination can be used to image O2 together with pH, Ca2+, mitochondrial membrane potential, cell death markers or cell/organelle specific markers. However, the main challenge of existing nanoparticle probes is their limited diffusion across thick (> 20-50 μm) 3D cell models such as tumor spheroids. Here, we present new class of polymeric nanoparticle probes having tunable size, charge, cell-penetrating ability, and reporter dyes. Being spectrally similar to the recently described MM2, PA2 and other O2 probes, they are 5-10 times brighter, demonstrate improved ratiometric response and their surface chemistry can be easily modified. With cultures of 2D and 3D cell models (fibroblasts, PC12 aggregates, HCT116 human colon cancer spheroids) we found cell-specific staining by these probes. However, the efficient staining of model of interest can be tuned by changing number of positive and negative surface groups at nanoparticle, to allow most efficient loading. We also demonstrate how real-time monitoring of oxygenation can be used to select optimal spheroid production with low variability in size and high cell viability.

  4. Fluorescence-Guided Probes of Aptamer-Targeted Gold Nanoparticles with Computed Tomography Imaging Accesses for in Vivo Tumor Resection

    PubMed Central

    Li, Cheng-Hung; Kuo, Tsung-Rong; Su, Hsin-Jan; Lai, Wei-Yun; Yang, Pan-Chyr; Chen, Jinn-Shiun; Wang, Di-Yan; Wu, Yi-Chun; Chen, Chia-Chun

    2015-01-01

    Recent development of molecular imaging probes for fluorescence-guided surgery has shown great progresses for determining tumor margin to execute the tissue resection. Here we synthesize the fluorescent gold nanoparticles conjugated with diatrizoic acid and nucleolin-targeted AS1411 aptamer. The nanoparticle conjugates exhibit high water-solubility, good biocompatibility, visible fluorescence and strong X-ray attenuation for computed tomography (CT) contrast enhancement. The fluorescent nanoparticle conjugates are applied as a molecular contrast agent to reveal the tumor location in CL1-5 tumor-bearing mice by CT imaging. Furthermore, the orange-red fluorescence emitting from the conjugates in the CL1-5 tumor can be easily visualized by the naked eyes. After the resection, the IVIS measurements show that the fluorescence signal of the nanoparticle conjugates in the tumor is greatly enhanced in comparison to that in the controlled experiment. Our work has shown potential application of functionalized nanoparticles as a dual-function imaging agent in clinical fluorescence-guided surgery. PMID:26507179

  5. MR-guided interstitial thermal therapy for the treatment of brain tumors with a multi-element ultrasound probe

    NASA Astrophysics Data System (ADS)

    Canney, Michael; Carpentier, Alexandre; Beccaria, Kevin; Souchon, Rémi; Chavrier, Françoise; Lafon, Cyril; Chapelon, Jean-Yves

    2012-10-01

    In this work, a new therapeutic ultrasound device is presented that is designed for performing minimally invasive thermal ablation of brain tumors under guidance with magnetic resonance imaging (MRI). The device consists of an array of ultrasound transducers, oriented on multiple faces of a flexible sheath with an integrated cooling system that can be directly inserted into the brain through a small burr hole in the skull. Heating can be monitored using real-time MRI and conformed to the tumor volume by varying the power to the individual elements on the probe. In this work, preliminary testing of the device was performed and included acoustic characterization, numerical simulations, and experiments in a clinical MRI system. Numerical simulations of the acoustic field and temperature rise during heating were compared with results of in vitro testing using bovine brain samples. The results demonstrate that the device has good MRI compatibility and is capable of generating output surface intensities of greater than 20 W/cm2, which is sufficient to ablate tissue at depths of more than 10 mm from the probe in less than four minutes of heating.

  6. Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

    NASA Astrophysics Data System (ADS)

    Qin, Zhengtao

    Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and

  7. Tissue distribution and real-time fluorescence measurement of a tumor-targeted nanodevice by a two photon optical fiber fluorescence probe

    NASA Astrophysics Data System (ADS)

    Thomas, Thommey P.; Ye, Jing Yong; Yang, Chu-Sheng; Myaing, Monthiri; Majoros, Istvan J.; Kotlyar, Alina; Cao, Zhengyi; Norris, Theodore B.; Baker, James R., Jr.

    2006-02-01

    Real-time fluorescence measurement in deep tumors in live animals (or humans) by conventional methods has significant challenges. We have developed a two-photon optical fiber fluorescence (TPOFF) probe as a minimally invasive technique for quantifying fluorescence in solid tumors in live mice. Here we demonstrate TPOFF for real-time measurements of targeted drug delivery dynamics to tumors in live mice. 50-femtosecond laser pulses at 800 nm were coupled into a single mode optical fiber and delivered into the tumor through a 27-gauge needle. Fluorescence was collected back through the same fiber, filtered, and detected with photon counting. Biocompatible dendrimer-based nanoparticles were used for targeted delivery of fluorescent materials into tumors. Dendrimers with targeting agent folic acid and fluorescent reporter 6-TAMRA (G5-6T-FA) were synthesized. KB cell tumors expressing high levels of FA receptors were developed in SCID mice. We initially demonstrated the specific uptake of the targeted conjugates into tumor, kidney and liver, using the TPOFF probe. The tumor fluorescence was then taken in live mice at 30 min, 2 h and 24 h with the TPOFF probe. G5-6T-FA accumulated in the tumor with maximum mean levels reaching 673 +/- 67 nM at the 2 h time point. In contrast, the levels of a control, non-targeted conjugate (G5-6T) at 2 h reached a level of only 136 +/- 28 nM in tumors, and decrease quickly. This indicates that the TPOFF probe can be used as a minimally invasive detection system for quantifying the specific targeting of a fluorescent nanodevice on a real-time basis.

  8. Azobenzene-caged sulforhodamine dyes: a novel class of ‘turn-on’ reactive probes for hypoxic tumor cell imaging

    NASA Astrophysics Data System (ADS)

    Chevalier, Arnaud; Piao, Wen; Hanaoka, Kenjiro; Nagano, Tetsuo; Renard, Pierre-Yves; Romieu, Anthony

    2015-12-01

    New sulforhodamine-based fluorescent ‘turn-on’ probes have been developed for the direct imaging of cellular hypoxia. Rapid access to this novel class of water-soluble ‘azobenzene-caged’ fluorophores was made possible through an easily-implementable azo-coupling reaction between a fluorescent primary arylamine derived from a sulforhodamine 101 scaffold (named SR101-NaphtNH 2 ) and a tertiary aniline whose N-substituents are neutral, cationic, or zwitterionic. The detection mechanism is based on the bioreductive cleavage of the azo bond that restores strong far-red fluorescence (emission maximum at 625 nm) by regenerating the original sulforhodamine SR101-NaphtNH 2 . This valuable fluorogenic response was obtained for the three ‘smart’ probes studied in this work, as shown by an in vitro assay using rat liver microsomes placed under aerobic and then under hypoxic conditions. Most importantly, the probe namely SR101-NaphtNH 2 -Hyp-diMe was successfully applied for imaging the hypoxic status of tumor cells (A549 cells).

  9. RGD-conjugated two-photon absorbing near-IR emitting fluorescent probes for tumor vascular imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Belfield, Kevin D.; Yue, Xiling; Morales, Alma R.; Githaiga, Grace W.; Woodward, Adam W.; Tang, Simon; Sawada, Junko; Komatsu, Masanobu; Liu, Xuan

    2016-03-01

    Observation of the activation and inhibition of angiogenesis processes is important in the progression of cancer. Application of targeting peptides, such as a small peptide that contains adjacent L-arginine (R), glycine (G) and L-aspartic acid (D) residues can afford high selectivity and deep penetration in vessel imaging. To facilitate deep tissue vasculature imaging, probes that can be excited via two-photon absorption (2PA) in the near-infrared (NIR) and subsequently emit in the NIR are essential. In this study, the enhancement of tissue image quality with RGD conjugates was investigated with new NIR-emitting pyranyl fluorophore derivatives in two-photon fluorescence microscopy. Linear and nonlinear photophysical properties of the new probes were comprehensively characterized; significantly the probes exhibited good 2PA over a broad spectral range from 700-1100 nm. Cell and tissue images were then acquired and examined, revealing deep penetration and high contrast with the new pyranyl RGD-conjugates up to 350 μm in tumor tissue.

  10. pH-responsive iron manganese silicate nanoparticles as T1-T2* dual-modal imaging probes for tumor diagnosis.

    PubMed

    Chen, Jian; Zhang, Wei-Jie; Guo, Zhen; Wang, Hai-Bao; Wang, Dong-Dong; Zhou, Jia-Jia; Chen, Qian-Wang

    2015-03-11

    Magnetic resonance imaging (MRI) probes can be concentrated in tumors through grafting targeting agents. However, the clinical application of such targeted MRI probes is largely limited because specific agents are only used to target specific characteristics of cancer cells. The development of the MRI probes that can be used regardless of tumor types or their developmental stages is highly appreciated. The acidic tumor microenvironments and acidic organelles (endosomes/lysosomes) in cancer cells are universal phenomena of solid tumors, and nanoparticles can also accumulate in tumor tissues by enhanced permeability and retention (EPR) effect. Here, we reported the synthesis of pH-responsive T1-T2* dual-modal contrast agents based on iron manganese silicate (FeMn(SiO4)) hollow nanospheres, which can release Mn(2+) ions in acidic environments, exhibiting excellent ability as agents for magnetic resonance and red fluorescence imaging. MRI for mouse models revealed that the nanoprobes could accumulate in tumors via EPR effect and then distinguish tumors from normal tissues with the synergistic effect of T1 and T2* signal only 10 min after intravenous injection. Fluorescence imaging demonstrated that the nanoprobes could be endocytosed into cancer cells and located at their lower pH compartments. Moreover, the hollow nanospheres showed no obvious toxicity and inflammation to the major organs of mice, which made them attractive diagnostic agents for different types of cancers.

  11. Probing the Backbone Function of Tumor Targeting Peptides by an Amide-to-Triazole Substitution Strategy.

    PubMed

    Valverde, Ibai E; Vomstein, Sandra; Fischer, Christiane A; Mascarin, Alba; Mindt, Thomas L

    2015-09-24

    Novel backbone-modified radiolabeled analogs based on the tumor targeting peptide bombesin were synthesized and fully evaluated in vitro and in vivo. We have recently introduced the use of 1,4-disubstituted 1,2,3-triazoles as metabolically stable trans-amide bond surrogates in radiolabeled peptides in order to improve their tumor targeting. As an extension of our approach, we now report several backbone-modified analogs of the studied bombesin peptide bearing multiple triazole substitutions. We investigated the effect of the modifications on several biological parameters including the internalization of the radiopeptidomimetics into tumor cells, their affinity toward the gastrin releasing peptide receptor (GRPr), metabolic stability in blood plasma, and biodistribution in mice bearing GRPr-expressing xenografts. The backbone-modified radiotracers exhibited a significantly increased resistance to proteolytic degradation. In addition, some of the radiopeptidomimetics retained a nanomolar affinity toward GRPr, resulting in an up to 2-fold increased tumor uptake in vivo in comparison to a (all amide bond) reference compound. PMID:26309061

  12. Fluorescence imaging of vascular endothelial growth factor in mice tumors using targeted liposome ICG probe

    NASA Astrophysics Data System (ADS)

    Zanganeh, Saeid; Xu, Yan; Backer, Marina V.; Backer, Joseph M.; Zhu, Quing

    2013-03-01

    Indocyanine Green encapsulating liposomes (Lip/ICG) and scVEGF-Lip/ICG liposomes, decorated with site-specifically lipidated engineered single-chain vascular endothelial growth factor (scVEGF) for targeting VEGF receptors were tested as potential tracers for fluorescent tomography. Two groups of experiments were conducted with tumor-bearing mice (n=4 to 6 per group) with tumors placed in a scattering medium at the imaging depths of 1.5 and 2.0 cm. Lip/ICG and scVEGF-Lip/ICG were injected intravenously in the amounts corresponding to 5 nmol of ICG/mouse. We detected kinetics of increase and decline in fluorescent signals in tumors for both imaging depths and for both targeted and untargeted Lip/ICG. Maximum fluorescent signals were approximately 2-fold higher at 1.5 cm vs. 2.0 cm imaging. A signal from untargeted Lip/ICG reached maximum at 15 min post-injection and then rapidly declined with t1/2 ~15 min. In contrast, a signal from targeted scVEGF-Lip/ICG reached maximum at 30 min post-injection and then slow declined with t1/2 ~60-90 min. Preferential retention of scVEGF-Lip(ICG) vs. Lip(ICG) was confirmed by the analysis of fluorescence in cryosections of corresponding tumors, harvested at 400 min post-injection. Our results suggest that targeted scVEGF-Lip/ICG can provide for significantly better post-injection time window for detection of relatively deeply seated tumors.

  13. Development of a novel fluorescent imaging probe for tumor hypoxia by use of a fusion protein with oxygen-dependent degradation domain of HIF-1α

    NASA Astrophysics Data System (ADS)

    Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Harada, Hiroshi; Hiraoka, Masahiro

    2007-02-01

    More malignant tumors contain more hypoxic regions. In hypoxic tumor cells, expression of a series of hypoxiaresponsive genes related to malignant phenotype such as angiogenesis and metastasis are induced. Hypoxia-inducible factor-1 (HIF-1) is a master transcriptional activator of such genes, and thus imaging of hypoxic tumor cells where HIF-1 is active, is important in cancer therapy. We have been developing PTD-ODD fusion proteins, which contain protein transduction domain (PTD) and the VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of HIF-1 alpha subunit (HIF-1α). Thus PTD-ODD fusion proteins can be delivered to any tissue in vivo through PTD function and specifically stabilized in hypoxic cells through ODD function. To investigate if PTD-ODD fusion protein can be applied to construct hypoxia-specific imaging probes, we first constructed a fluorescent probe because optical imaging enable us to evaluate a probe easily, quickly and economically in a small animal. We first construct a model fusion porein PTD-ODD-EGFP-Cy5.5 named POEC, which is PTD-ODD protein fused with EGFP for in vitro imaging and stabilization of fusion protein, and conjugated with a near-infrared dye Cy5.5. This probe is designed to be degraded in normoxic cells through the function of ODD domain and followed by quick clearance of free fluorescent dye. On the other hand, this prove is stabilized in hypoxic tumor cells and thus the dye is stayed in the cells. Between normoxic and hypoxic conditions, the difference in the clearance rate of the dye will reveals suited contrast for tumor-hypoxia imaging. The optical imaging probe has not been optimized yet but the results presented here exhibit a potential of PTD-ODD fusion protein as a hypoxia-specific imaging probe.

  14. Engineering Agatoxin, a Cystine-Knot Peptide from Spider Venom, as a Molecular Probe for In Vivo Tumor Imaging

    PubMed Central

    Norton, Heidi K.; Cochran, Jennifer R.

    2013-01-01

    Background Cystine-knot miniproteins, also known as knottins, have shown great potential as molecular scaffolds for the development of targeted therapeutics and diagnostic agents. For this purpose, previous protein engineering efforts have focused on knottins based on the Ecballium elaterium trypsin inhibitor (EETI) from squash seeds, the Agouti-related protein (AgRP) neuropeptide from mammals, or the Kalata B1 uterotonic peptide from plants. Here, we demonstrate that Agatoxin (AgTx), an ion channel inhibitor found in spider venom, can be used as a molecular scaffold to engineer knottins that bind with high-affinity to a tumor-associated integrin receptor. Methodology/Principal Findings We used a rational loop-grafting approach to engineer AgTx variants that bound to αvβ3 integrin with affinities in the low nM range. We showed that a disulfide-constrained loop from AgRP, a structurally-related knottin, can be substituted into AgTx to confer its high affinity binding properties. In parallel, we identified amino acid mutations required for efficient in vitro folding of engineered integrin-binding AgTx variants. Molecular imaging was used to evaluate in vivo tumor targeting and biodistribution of an engineered AgTx knottin compared to integrin-binding knottins based on AgRP and EETI. Knottin peptides were chemically synthesized and conjugated to a near-infrared fluorescent dye. Integrin-binding AgTx, AgRP, and EETI knottins all generated high tumor imaging contrast in U87MG glioblastoma xenograft models. Interestingly, EETI-based knottins generated significantly lower non-specific kidney imaging signals compared to AgTx and AgRP-based knottins. Conclusions/Significance In this study, we demonstrate that AgTx, a knottin from spider venom, can be engineered to bind with high affinity to a tumor-associated receptor target. This work validates AgTx as a viable molecular scaffold for protein engineering, and further demonstrates the promise of using tumor

  15. Probing the compressibility of tumor cell nuclei by combined atomic force-confocal microscopy.

    PubMed

    Krause, Marina; Te Riet, Joost; Wolf, Katarina

    2013-12-01

    The cell nucleus is the largest and stiffest organelle rendering it the limiting compartment during migration of invasive tumor cells through dense connective tissue. We here describe a combined atomic force microscopy (AFM)-confocal microscopy approach for measurement of bulk nuclear stiffness together with simultaneous visualization of the cantilever-nucleus contact and the fate of the cell. Using cantilevers functionalized with either tips or beads and spring constants ranging from 0.06-10 N m(-1), force-deformation curves were generated from nuclear positions of adherent HT1080 fibrosarcoma cell populations at unchallenged integrity, and a nuclear stiffness range of 0.2 to 2.5 kPa was identified depending on cantilever type and the use of extended fitting models. Chromatin-decondensating agent trichostatin A (TSA) induced nuclear softening of up to 50%, demonstrating the feasibility of our approach. Finally, using a stiff bead-functionalized cantilever pushing at maximal system-intrinsic force, the nucleus was deformed to 20% of its original height which after TSA treatment reduced further to 5% remaining height confirming chromatin organization as an important determinant of nuclear stiffness. Thus, combined AFM-confocal microscopy is a feasible approach to study nuclear compressibility to complement concepts of limiting nuclear deformation in cancer cell invasion and other biological processes.

  16. Probing the compressibility of tumor cell nuclei by combined atomic force-confocal microscopy

    NASA Astrophysics Data System (ADS)

    Krause, Marina; te Riet, Joost; Wolf, Katarina

    2013-12-01

    The cell nucleus is the largest and stiffest organelle rendering it the limiting compartment during migration of invasive tumor cells through dense connective tissue. We here describe a combined atomic force microscopy (AFM)-confocal microscopy approach for measurement of bulk nuclear stiffness together with simultaneous visualization of the cantilever-nucleus contact and the fate of the cell. Using cantilevers functionalized with either tips or beads and spring constants ranging from 0.06-10 N m-1, force-deformation curves were generated from nuclear positions of adherent HT1080 fibrosarcoma cell populations at unchallenged integrity, and a nuclear stiffness range of 0.2 to 2.5 kPa was identified depending on cantilever type and the use of extended fitting models. Chromatin-decondensating agent trichostatin A (TSA) induced nuclear softening of up to 50%, demonstrating the feasibility of our approach. Finally, using a stiff bead-functionalized cantilever pushing at maximal system-intrinsic force, the nucleus was deformed to 20% of its original height which after TSA treatment reduced further to 5% remaining height confirming chromatin organization as an important determinant of nuclear stiffness. Thus, combined AFM-confocal microscopy is a feasible approach to study nuclear compressibility to complement concepts of limiting nuclear deformation in cancer cell invasion and other biological processes.

  17. Dialkoxyquinazolines: Screening Epidermal Growth Factor ReceptorTyrosine Kinase Inhibitors for Potential Tumor Imaging Probes

    SciTech Connect

    VanBrocklin, Henry F.; Lim, John K.; Coffing, Stephanie L.; Hom,Darren L.; Negash, Kitaw; Ono, Michele Y.; Hanrahan, Stephen M.; Taylor,Scott E.; Vanderpoel, Jennifer L.; Slavik, Sarah M.; Morris, Andrew B.; Riese II, David J.

    2005-09-01

    The epidermal growth factor receptor (EGFR), a long-standingdrug development target, is also a desirable target for imaging. Sixteendialkoxyquinazoline analogs, suitable for labeling with positron-emittingisotopes, have been synthesized and evaluated in a battery of in vitroassays to ascertain their chemical and biological properties. Thesecharacteristics provided the basis for the adoption of a selection schemato identify lead molecules for labeling and in vivo evaluation. A newEGFR tyrosine kinase radiometric binding assay revealed that all of thecompounds possessed suitable affinity (IC50 = 0.4 - 51 nM) for the EGFRtyrosine kinase. All of the analogs inhibited ligand-induced EGFRtyrosine phosphorylation (IC50 = 0.8 - 20 nM). The HPLC-estimatedoctanol/water partition coefficients ranged from 2.0-5.5. Four compounds,4-(2'-fluoroanilino)- and 4-(3'-fluoroanilino)-6,7-diethoxyquinazoline aswell as 4-(3'-chloroanilino)- and4-(3'-bromoanilino)-6,7-dimethoxyquinazoline, possess the bestcombination of characteristics that warrant radioisotope labeling andfurther evaluation in tumor-bearing mice.

  18. Magnetically engineered Cd-free quantum dots as dual-modality probes for fluorescence/magnetic resonance imaging of tumors.

    PubMed

    Ding, Ke; Jing, Lihong; Liu, Chunyan; Hou, Yi; Gao, Mingyuan

    2014-02-01

    Magnetically engineered Cd-free CuInS2@ZnS:Mn quantum dots (QDs) were designed, synthesized, and evaluated as potential dual-modality probes for fluorescence and magnetic resonance imaging (MRI) of tumors in vivo. The synthesis of Mn-doped core-shell structured CuInS2@ZnS mainly comprised three steps, i.e., the preparation of fluorescent CuInS2 seeds, the particle surface coating of ZnS, and the Mn-doping of the ZnS shells. Systematic spectroscopy studies were carried out to illustrate the impacts of ZnS coating and the following Mn-doping on the optical properties of the QDs. In combination with conventional fluorescence, fluorescence excitation, and time-resolved fluorescence measurements, the structure of CuInS2@ZnS:Mn QDs prepared under optimized conditions presented a Zn gradient CuInS2 core and a ZnS outer shell, while Mn ions were mainly located in the ZnS shell, which well balanced the optical and magnetic properties of the resultant QDs. For the following in vivo imaging experiments, the hydrophobic CuInS2@ZnS:Mn QDs were transferred into water upon ligand exchange reactions by replacing the 1-dodecanethiol ligand with dihydrolipoic acid-poly(ethylene glycol) (DHLA-PEG) ligand. The MTT assays based on HeLa cells were carried out to evaluate the cytotoxicity of the current Cd-free CuInS2@ZnS:Mn QDs for comparing with that of water soluble CdTe QDs. Further in vivo fluorescence and MR imaging experiments suggested that the PEGylated CuInS2@ZnS:Mn QDs could well target both subcutaneous and intraperitoneal tumors in vivo.

  19. Tumor

    MedlinePlus

    ... plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by viruses are: Cervical cancer (human papillomavirus) Hepatocellular carcinoma (hepatitis B and hepatitis C ...

  20. Comparison of surface micro-structured and plasmonic all-fiber delivery probes for laser-induced thermotherapy of tumor cells

    NASA Astrophysics Data System (ADS)

    Gassino, Riccardo; Dhara, Papiya; Liu, Yu; Yu, Hao; Braglia, Andrea; Olivero, Massimo; Vallan, Alberto; Perrone, Guido

    2016-03-01

    The paper compares two different approaches to design an innovative probe with optimized heated area for laser ablation of solid tumors: micro-patterning of the fiber delivery tip, and exploitation of the dissipation of plasmonic waves at the metal-dielectric interface. Both probes integrate a fiber Bragg grating for real- time monitoring of the obtained temperature increase to provide feedback to surgeons in practical applications. Experimental characterizations carried out using liver phantoms and ex-vivo porcine livers have demonstrated that both approaches can be used for the devised application, although further optimizations and tests are still necessary before clinical assessment.

  1. Imaging integrin α(v)β(3) positive glioma with a novel RGD dimer probe and the impact of antiangiogenic agent (Endostar) on its tumor uptake.

    PubMed

    Wu, Hua; Chen, Haojun; Sun, Yonghong; Wan, Ying; Wang, Fan; Jia, Bing; Su, Xinhui

    2013-07-10

    Integrin αvβ3 has been recognized to play an important role in angiogenesis, tumor growth and metastasis. It will be of interest to apply this promising target for tumor imaging and visualization of tumor angiogenesis in vivo. In this study, a novel integrin αvβ3 targetting imaging probe, (99m)Tc-HYNIC-E[c(RGDfK)]2, was used to investigate the glioma uptake in vitro and in vivo before and after treatment with an antiangiogenic agent, endostar. The results indicated that U87MG glioma cells have high expression of integrin αvβ3 and special uptake of (99m)Tc-HYNIC-E[c(RGDfK)]2 both in cell line and in tumor xenograft. The endostatin analogue endostar can inhibit the expression of integrin αvβ3 receptors in both U87MG cells in vitro and glioma tissues, which suggested that integrin pathway may play a role in antiangiogenic effect of Endostar. (99m)Tc-HYNIC-E[c(RGDfK)]2 may be a promising molecular imaging probe for integrin αvβ3 positive tumor imaging and open up the possibility to establish an molecular imaging modality for assessment of tomor antiangiogenic therapy.

  2. In vivo imaging of intraperitoneally disseminated tumors in model mice by using activatable fluorescent small-molecular probes for activity of cathepsins.

    PubMed

    Fujii, Tomohiko; Kamiya, Mako; Urano, Yasuteru

    2014-10-15

    It is difficult to completely remove carcinomas in unguided ablative surgery because they cannot be distinguished with the unaided human eye. Therefore, in order to precisely visualize tiny tumors and the borders between cancerous lesions and normal tissues, we have been developing fluorescence probes activatable only in cancer cells. We previously reported the hydroxymethylrhodamine green (HMRG)-based fluorescence probe gGlu-HMRG for γ-glutamyltransferase (GGT), which is overexpressed in a variety of cancer cells, and we showed that it enables in vivo rapid detection of human ovarian cancer SHIN-3 nodules with a high tumor-to-background (T/B) fluorescence ratio in model mice. However, cancer cell lines with low GGT expression could hardly be detected with gGlu-HMRG. Here we developed two new HMRG-based fluorescence probes for the cathepsin family of cysteine proteases, including cathepsin B (CatB) and cathepsin L (CatL), which show increased expression and/or activity, secretion, and altered localization in many kinds of cancer cells. The developed probes, Z-Phe-Arg-HMRG and Z-Arg-Arg-HMRG, are colorless and nonfluorescent at the physiological pH of 7.4, but are hydrolyzed to HMRG upon reaction with purified cathepsins, resulting in a more than 200-fold fluorescence increase. These probes could visualize human ovarian cancer cell lines SHIN-3, SK-OV-3, and OVCAR-3, of which the latter two were hardly detectable with gGlu-HMRG. Z-Phe-Arg-HMRG showed higher applicability than Z-Arg-Arg-HMRG for in vivo imaging, and we confirmed that 0.5-mm-sized SK-OV-3 tumor nodules disseminated on the mesentery in a mouse model could be rapidly visualized by Z-Phe-Arg-HMRG, with a T/B fluorescence ratio of 4.2. Further, intraperitoneally disseminated tumor could be visualized in real time in vivo by fluorescence endoscopy after spraying Z-Phe-Arg-HMRG, with a T/B ratio of 3. In conclusion, our HMRG-based activatable probes targeted to cathepsins have expanded the detectable range

  3. Synthesis and evaluation of a radioiodinated 4,6-diaryl-3-cyano-2-pyridinone derivative as a survivin targeting SPECT probe for tumor imaging.

    PubMed

    Fuchigami, Takeshi; Mizoguchi, Tatsuya; Ishikawa, Natsumi; Haratake, Mamoru; Yoshida, Sakura; Magata, Yasuhiro; Nakayama, Morio

    2016-02-01

    Survivin is overexpressed in most of the cancerous tissues but not in terminally differentiated normal tissues, making it an attractive target for diagnosis and therapy of various types of cancers. In this study, we aimed to develop 4,6-diaryl-3-cyano-2-pyridinone (DCP) derivatives, as novel cancer imaging probes that target survivin. Chloro and iodo analogs of DCP (CDCP and IDCP, respectively) were successfully synthesized by using a previously unreported carbon monoxide-free procedure. IDCP exhibited a slightly higher binding affinity for recombinant human survivin (Kd=34 nM) than that of CDCP (Kd=44 nM). Fluorescence staining indicated that both CDCP and IDCP showed high signals in MDA-MB-231 cells with high levels of survivin expression. Significantly low fluorescent signals were observed in MCF-10A cells, which showed low levels of survivin expression. [(125)I]IDCP was synthesized for the application of IDCP to single photon emission computed tomography (SPECT) imaging. Quantitative in vitro binding of [(125)I]IDCP in cell cultures showed results consistent to those observed after fluorescent staining. In vivo biodistribution studies in tumor-bearing mice demonstrated that the tumor uptake of [(125)I]IDCP increased gradually with time and was 0.65% injected dose per gram (% ID/g) at 180 min. The maximum tumor/blood and tumor/muscle ratio at 60 min were 0.87 and 2.27, respectively, indicating inadequate [(125)I]IDCP accumulation in tumors necessary for in vivo imaging. Although further structural modifications are necessary to improve pharmacokinetic properties of IDCP, this study demonstrates the feasibility of using the DCP backbone as a scaffold for the development of survivin-targeting tumor imaging probes. PMID:26733475

  4. High-sensitivity detection of breast tumors in vivo by use of a pH-sensitive near-infrared fluorescence probe

    NASA Astrophysics Data System (ADS)

    Mathejczyk, Julia Eva; Pauli, Jutta; Dullin, Christian; Resch-Genger, Ute; Alves, Frauke; Napp, Joanna

    2012-07-01

    We investigated the potential of the pH-sensitive dye, CypHer5E, conjugated to Herceptin (pH-Her) for the sensitive detection of breast tumors in mice using noninvasive time-domain near-infrared fluorescence imaging and different methods of data analysis. First, the fluorescence properties of pH-Her were analyzed as function of pH and/or dye-to-protein ratio, and binding specificity was confirmed in cell-based assays. Subsequently, the performance of pH-Her in nude mice bearing orthotopic HER2-positive (KPL-4) and HER2-negative (MDA-MB-231) breast carcinoma xenografts was compared to that of an always-on fluorescent conjugate Alexa Fluor 647-Herceptin (Alexa-Her). Subtraction of autofluorescence and lifetime (LT)-gated image analyses were performed for background fluorescence suppression. In mice bearing HER2-positive tumors, autofluorescence subtraction together with the selective fluorescence enhancement of pH-Her solely in the tumor's acidic environment provided high contrast-to-noise ratios (CNRs). This led to an improved sensitivity of tumor detection compared to Alexa-Her. In contrast, LT-gated imaging using LTs determined in model systems did not improve tumor-detection sensitivity in vivo for either probe. In conclusion, pH-Her is suitable for sensitive in vivo monitoring of HER2-expressing breast tumors with imaging in the intensity domain and represents a promising tool for detection of weak fluorescent signals deriving from small tumors or metastases.

  5. Evaluation of 6-([18F] fluoroacetamido)-1-hexanoic-anilide (18F-FAHA) as imaging probe in tumor xenograft mice model

    NASA Astrophysics Data System (ADS)

    Li, Fiona; Cho, Sung Ju; Yu, Lihai; Hudson, Robert H. E.; Luyt, Leonard G.; Pin, Christopher L.; Kovacs, Michael S.; Koropatnick, James; Lee, Ting-Yim

    2016-03-01

    Alteration in genetic expression is as important as gene mutation in cancer development and proliferation. Epigenetic changes affect gene expression without altering the DNA sequence. Histone deacetylase (HDAC), an enzyme facilitating histone remodelling, can lead to silencing of tumor suppressor genes making HDAC inhibitors viable anticancer drugs against tumors with increased activity of the enzyme. In this study we evaluated 18F-fluroacetamido-1-hexanoicanilide (18F-FAHA), an artificial HDAC substrate, as imaging probe of HDAC activity of human tumor xenografts in immunocompromised host mice. Human breast and melanoma cell lines, MDA-MB-468 and MDA-MB-435 respectively, known to overexpress HDAC activity were xenografted into immunocompromised mice and HDAC activity was imaged using 18F-FAHA. The melanoma group was treated with saline, SAHA (suberoylanilide hydroxamic acid, an approved anticancer HDAC inhibitor) in DMSO, or DMSO as positive control. Tracer kinetic modelling and SUV were used to estimate HDAC activity from dynamic PET data. Both breast tumor and melanoma group showed great variability in binding rate constant (BRC) of 18F-FAHA suggesting highly variable inter- and intra-tumoral HDAC activity. For the SAHA treated melanoma group, HDAC activity, as monitored by BRC of 18F-FAHA, decreased more than the two (positive and negative) control groups but not tumor growth. Our preliminary study showed that noninvasive PET imaging with 18F-FAHA has the potential to identify patients for whom treatment with HDAC inhibitors are appropriate, to assess the effectiveness of that treatment as an early marker of target reduction, and also eliminate the need for invasive tissue biopsy to individualize treatment.

  6. Tumor progression in murine leukemia virus-induced T-cell lymphomas: monitoring clonal selections with viral and cellular probes.

    PubMed Central

    Cuypers, H T; Selten, G C; Zijlstra, M; de Goede, R E; Melief, C J; Berns, A J

    1986-01-01

    Clonal selections occurring during the progression of Moloney murine leukemia virus (MuLV)-induced T-cell lymphomas in mice were examined in primary and transplanted tumors by monitoring various molecular markers: proviral integration patterns, MuLV insertions near c-myc and pim-1, and rearrangements of the immunoglobulin heavy chain and beta-chain T-cell receptor genes. The results were as follows. Moloney MuLV frequently induced oligoclonal tumors with proviral insertions near c-myc or pim-1 in the independent clones. Moloney MuLV acted as a highly efficient insertional mutagen, able to activate different (putative) oncogenes in one cell lineage. Clonal selections during tumor progression were frequently marked by the acquisition of new proviral integrations. Independent tumor cell clones exhibited a homing preference upon transplantation in syngeneic hosts and were differently affected by the route of transplantation. Images PMID:3091854

  7. Real-Time Tracking and In Vivo Visualization of β-Galactosidase Activity in Colorectal Tumor with a Ratiometric Near-Infrared Fluorescent Probe.

    PubMed

    Gu, Kaizhi; Xu, Yisheng; Li, Hui; Guo, Zhiqian; Zhu, Shaojia; Zhu, Shiqin; Shi, Ping; James, Tony D; Tian, He; Zhu, Wei-Hong

    2016-04-27

    Development of "smart" noninvasive bioimaging probes for trapping specific enzyme activities is highly desirable for cancer therapy in vivo. Given that β-galactosidase (β-gal) is an important biomarker for cell senescence and primary ovarian cancers, we design an enzyme-activatable ratiometric near-infrared (NIR) probe (DCM-βgal) for the real-time fluorescent quantification and trapping of β-gal activity in vivo and in situ. DCM-βgal manifests significantly ratiometric and turn-on NIR fluorescent signals simultaneously in response to β-gal concentration, which makes it favorable for monitoring dynamic β-gal activity in vivo with self-calibration in fluorescent mode. We exemplify DCM-βgal for the ratiometric tracking of endogenously overexpressed β-gal distribution in living 293T cells via the lacZ gene transfection method and OVCAR-3 cells, and further realize real-time in vivo bioimaging of β-gal activity in colorectal tumor-bearing nude mice. Advantages of our system include light-up ratiometric NIR fluorescence with large Stokes shift, high photostability, and pH independency under the physiological range, allowing for the in vivo real-time evaluation of β-gal activity at the tumor site with high-resolution three-dimensional bioimaging for the first time. Our work provides a potential tool for in vivo real-time tracking enzyme activity in preclinical applications. PMID:27054782

  8. Real-Time Tracking and In Vivo Visualization of β-Galactosidase Activity in Colorectal Tumor with a Ratiometric Near-Infrared Fluorescent Probe.

    PubMed

    Gu, Kaizhi; Xu, Yisheng; Li, Hui; Guo, Zhiqian; Zhu, Shaojia; Zhu, Shiqin; Shi, Ping; James, Tony D; Tian, He; Zhu, Wei-Hong

    2016-04-27

    Development of "smart" noninvasive bioimaging probes for trapping specific enzyme activities is highly desirable for cancer therapy in vivo. Given that β-galactosidase (β-gal) is an important biomarker for cell senescence and primary ovarian cancers, we design an enzyme-activatable ratiometric near-infrared (NIR) probe (DCM-βgal) for the real-time fluorescent quantification and trapping of β-gal activity in vivo and in situ. DCM-βgal manifests significantly ratiometric and turn-on NIR fluorescent signals simultaneously in response to β-gal concentration, which makes it favorable for monitoring dynamic β-gal activity in vivo with self-calibration in fluorescent mode. We exemplify DCM-βgal for the ratiometric tracking of endogenously overexpressed β-gal distribution in living 293T cells via the lacZ gene transfection method and OVCAR-3 cells, and further realize real-time in vivo bioimaging of β-gal activity in colorectal tumor-bearing nude mice. Advantages of our system include light-up ratiometric NIR fluorescence with large Stokes shift, high photostability, and pH independency under the physiological range, allowing for the in vivo real-time evaluation of β-gal activity at the tumor site with high-resolution three-dimensional bioimaging for the first time. Our work provides a potential tool for in vivo real-time tracking enzyme activity in preclinical applications.

  9. Probe-Based Confocal Laser Endomicroscopy for Imaging TRAIL-Expressing Mesenchymal Stem Cells to Monitor Colon Xenograft Tumors In Vivo

    PubMed Central

    Zhang, Zhen; Li, Ming; Chen, Feixue; Li, Lixiang; Liu, Jun; Li, Zhen; Ji, Rui; Zuo, Xiuli; Li, Yanqing

    2016-01-01

    Introduction Mesenchymal stem cells (MSCs) can serve as vehicles for therapeutic genes. However, little is known about MSC behavior in vivo. Here, we demonstrated that probe-based confocal laser endomicroscopy (pCLE) can be used to track MSCs in vivo and individually monitor tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) gene expression within carcinomas. Methods Isolated BALB/c nu/nu mice MSCs (MSCs) were characterized and engineered to co-express the TRAIL and enhanced green fluorescent protein (EGFP) genes. The number of MSCs co-expressing EGFP and TRAIL (TRAIL-MSCs) at tumor sites was quantified with pCLE in vivo, while their presence was confirmed using immunofluorescence (IF) and quantitative polymerase chain reaction (qPCR). The therapeutic effects of TRAIL-MSCs were evaluated by measuring the volumes and weights of subcutaneous HT29-derived xenograft tumors. Results Intravital imaging of the subcutaneous xenograft tumors revealed that BALB/c mice treated with TRAIL-MSCs exhibited specific cellular signals, whereas no specific signals were observed in the control mice. The findings from the pCLE images were consistent with the IF and qPCR results. Conclusion The pCLE results indicated that endomicroscopy could effectively quantify injected MSCs that homed to subcutaneous xenograft tumor sites in vivo and correlated well with the therapeutic effects of the TRAIL gene. By applying pCLE for the in vivo monitoring of cellular trafficking, stem cell-based anticancer gene therapeutic approaches might be feasible and attractive options for individualized clinical treatments. PMID:27617958

  10. Electrochemical detection of DNA binding by tumor suppressor p53 protein using osmium-labeled oligonucleotide probes and catalytic hydrogen evolution at the mercury electrode.

    PubMed

    Němcová, Kateřina; Sebest, Peter; Havran, Luděk; Orság, Petr; Fojta, Miroslav; Pivoňková, Hana

    2014-09-01

    In this paper, we present an electrochemical DNA-protein interaction assay based on a combination of protein-specific immunoprecipitation at magnetic beads (MBIP) with application of oligonucleotide (ON) probes labeled with an electroactive oxoosmium complex (Os,bipy). We show that double-stranded ONs bearing a dT20 tail labeled with Os,bipy are specifically recognized by the tumor suppressor p53 protein according to the presence or absence of a specific binding site (p53CON) in the double-stranded segment. We demonstrate the applicability of the Os,bipy-labeled probes in titration as well as competition MBIP assays to evaluate p53 relative affinity to various sequence-specific or structurally distinct unlabeled DNA substrates upon modulation of the p53-DNA binding by monoclonal antibodies used for the immunoprecipitation. To detect the p53-bound osmium-labeled probes, we took advantage of a catalytic peak yielded by Os,bipy-modified DNA at the mercury-based electrodes, allowing facile determination of subnanogram quantities of the labeled oligonucleotides. Versatility of the electrochemical MBIP technique and its general applicability in studies of any DNA-binding protein is discussed.

  11. Molecular imaging of human tumor cells that naturally overexpress type 2 cannabinoid receptors using a quinolone-based near-infrared fluorescent probe

    NASA Astrophysics Data System (ADS)

    Wu, Zhiyuan; Shao, Pin; Zhang, Shaojuan; Ling, Xiaoxi; Bai, Mingfeng

    2014-07-01

    Cannabinoid CB2 receptors (CB2R) hold promise as therapeutic targets for treating diverse diseases, such as cancers, neurodegenerative diseases, pain, inflammation, osteoporosis, psychiatric disorders, addiction, and immune disorders. However, the fundamental role of CBR in the regulation of diseases remains unclear, largely due to a lack of reliable imaging tools for the receptors. The goal of this study was to develop a CBR-targeted molecular imaging probe and evaluate the specificity of the probe using human tumor cells that naturally overexpress CBR. To synthesize the CBR-targeted probe (NIR760-Q), a conjugable CBR ligand based on the quinolone structure was first prepared, followed by bioconjugation with a near-infrared (NIR) fluorescent dye, NIR760. In vitro fluorescence imaging and competitive binding studies showed higher uptake of NIR760-Q than free NIR760 dye in Jurkat human acute T-lymphoblastic leukemia cells. In addition, the high uptake of NIR760-Q was significantly inhibited by the blocking agent, 4-quinolone-3-carboxamide, indicating specific binding of NIR760-Q to the target receptors. These results indicate that the NIR760-Q has potential in diagnostic imaging of CBR positive cancers and elucidating the role of CBR in the regulation of disease progression.

  12. Synthesis and biological evaluation of ¹⁸F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging.

    PubMed

    Chiotellis, Aristeidis; Mu, Linjing; Müller, Adrienne; Selivanova, Svetlana V; Keller, Claudia; Schibli, Roger; Krämer, Stefanie D; Ametamey, Simon M

    2013-01-01

    In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[(18)F]fluoropropyl)-DL-tryptophan ([(18)F]2-FPTRP) and 5-(3-[(18)F]fluoro-propyl)-DL-tryptophan ([(18)F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [(18)F]fluorination in 29-34% decay corrected yields with radiochemical purity over 99%. In vitro cell uptake assays showed that both compounds are substrates for amino acid transport and enter small cell lung cancer cells (NCI-H69) most probably almost exclusively via large neutral amino acids transporter(s) (LAT). Small animal PET imaging with xenograft bearing mice revealed high tumor/background ratios for [(18)F]2-FPTRP comparable to the well established tyrosine analog O-(2-[(18)F]fluroethyl)-L-tyrosine ([(18)F]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation.

  13. Quantitative detection of the tumor-associated antigen large external antigen in colorectal cancer tissues and cells using quantum dot probe.

    PubMed

    Wang, Shuo; Li, Wanming; Yuan, Dezheng; Song, Jindan; Fang, Jin

    2016-01-01

    The large external antigen (LEA) is a cell surface glycoprotein that has been proven to be highly expressed in colorectal cancer (CRC) as a tumor-associated antigen. To evaluate and validate the relationship between LEA expression and clinical characteristics of CRC with high efficiency, LEA expression levels were detected in 85 tissue blocks from CRC patients by quantum dot-based immunohistochemistry (QD-IHC) combined with imaging quantitative analysis using quantum dots with a 605 nm emission wavelength (QD605) conjugated to an ND-1 monoclonal antibody against LEA as a probe. Conventional IHC was performed in parallel for comparison. Both QD-IHC and conventional IHC showed that LEA was specifically expressed in CRC, but not in non-CRC tissues, and high LEA expression was significantly associated with a more advanced T-stage (P<0.05), indicating that LEA is likely to serve as a CRC prognostic marker. Compared with conventional IHC, receiver operating characteristic analysis revealed that QD-IHC possessed higher sensitivity, resulting in an increased positive detection rate of CRC, from 70.1% to 89.6%. In addition, a simpler operation, objective analysis of results, and excellent repeatability make QD-IHC an attractive alternative to conventional IHC in clinical practice. Furthermore, to explore whether the QD probes can be utilized to quantitatively detect living cells or single cells, quantum dot-based immunocytochemistry (QD-ICC) combined with imaging quantitative analysis was developed to evaluate LEA expression in several CRC cell lines. It was demonstrated that QD-ICC could also predict the correlation between LEA expression and the T-stage characteristics of the cell lines, which was confirmed by flow cytometry. The results of this study indicate that QD-ICC has the potential to noninvasively detect rare circulating tumor cells in clinical samples in real clinical applications.

  14. Trimodal color-fluorescence-polarization endoscopy aided by a tumor selective molecular probe accurately detects flat lesions in colitis-associated cancer

    PubMed Central

    Charanya, Tauseef; York, Timothy; Bloch, Sharon; Sudlow, Gail; Liang, Kexian; Garcia, Missael; Akers, Walter J.; Rubin, Deborah; Gruev, Viktor; Achilefu, Samuel

    2014-01-01

    Abstract. Colitis-associated cancer (CAC) arises from premalignant flat lesions of the colon, which are difficult to detect with current endoscopic screening approaches. We have developed a complementary fluorescence and polarization reporting strategy that combines the unique biochemical and physical properties of dysplasia and cancer for real-time detection of these lesions. Using azoxymethane-dextran sodium sulfate (AOM-DSS) treated mice, which recapitulates human CAC and dysplasia, we show that an octapeptide labeled with a near-infrared (NIR) fluorescent dye selectively identified all precancerous and cancerous lesions. A new thermoresponsive sol-gel formulation allowed topical application of the molecular probe during endoscopy. This method yielded high contrast-to-noise ratios (CNR) between adenomatous tumors (20.6±1.65) and flat lesions (12.1±1.03) and surrounding uninvolved colon tissue versus CNR of inflamed tissues (1.62±0.41). Incorporation of nanowire-filtered polarization imaging into NIR fluorescence endoscopy shows a high depolarization contrast in both adenomatous tumors and flat lesions in CAC, reflecting compromised structural integrity of these tissues. Together, the real-time polarization imaging provides real-time validation of suspicious colon tissue highlighted by molecular fluorescence endoscopy. PMID:25473883

  15. Trimodal color-fluorescence-polarization endoscopy aided by a tumor selective molecular probe accurately detects flat lesions in colitis-associated cancer

    NASA Astrophysics Data System (ADS)

    Charanya, Tauseef; York, Timothy; Bloch, Sharon; Sudlow, Gail; Liang, Kexian; Garcia, Missael; Akers, Walter J.; Rubin, Deborah; Gruev, Viktor; Achilefu, Samuel

    2014-12-01

    Colitis-associated cancer (CAC) arises from premalignant flat lesions of the colon, which are difficult to detect with current endoscopic screening approaches. We have developed a complementary fluorescence and polarization reporting strategy that combines the unique biochemical and physical properties of dysplasia and cancer for real-time detection of these lesions. Using azoxymethane-dextran sodium sulfate (AOM-DSS) treated mice, which recapitulates human CAC and dysplasia, we show that an octapeptide labeled with a near-infrared (NIR) fluorescent dye selectively identified all precancerous and cancerous lesions. A new thermoresponsive sol-gel formulation allowed topical application of the molecular probe during endoscopy. This method yielded high contrast-to-noise ratios (CNR) between adenomatous tumors (20.6±1.65) and flat lesions (12.1±1.03) and surrounding uninvolved colon tissue versus CNR of inflamed tissues (1.62±0.41). Incorporation of nanowire-filtered polarization imaging into NIR fluorescence endoscopy shows a high depolarization contrast in both adenomatous tumors and flat lesions in CAC, reflecting compromised structural integrity of these tissues. Together, the real-time polarization imaging provides real-time validation of suspicious colon tissue highlighted by molecular fluorescence endoscopy.

  16. scVEGF Microbubble Ultrasound Contrast Agents: A Novel Probe for Ultrasound Molecular Imaging of Tumor Angiogenesis

    PubMed Central

    Christopher R., Anderson; Joshua J., Rychak; Marina, Backer; Joseph, Backer; Klaus, Ley; Alexander L., Klibanov

    2012-01-01

    Objective To develop a novel microbubble (MB) ultrasound contrast agent covalently coupled to a recombinant single-chain vascular endothelial growth factor construct (scVEGF) through uniform site-specific conjugation for ultrasound imaging of tumor angiogenesis. Methods Ligand conjugation to maleimide-bearing MB by thioether bonding was first validated with a fluorophore (BODIPY-cystine), and covalently bound dye was detected by fluorometry and flow cytometry. MBs were subsequently site-specifically conjugated to cysteine-containing Cys-tag in scVEGF, and bound scVEGF was quantified by enzyme-linked immunosorbent assay. Targeted adhesion of scVEGF-MB was investigated with in vitro parallel plate flow chamber assays with recombinant murine VEGFR-2 substrates and human VEGFR-2-expressing porcine endothelial cells (PAE/KDR). A wall-less ultrasound flow phantom, with flow channels coated with immobilized VEGFR-2, was used to detect adhesion of scVEGF-MB with contrast ultrasound imaging. A murine model of colon adenocarcinoma was used to assess retention of scVEGF-MB with contrast ultrasound imaging during tumor angiogenesis in vivo. Results Proof-of-principle of ligand conjugation to maleimide-bearing MB was demonstrated with a BODIPY-cysteine fluorophore. Conjugation of BODIPY to MB saturated at 10-fold molar excess BODIPY relative to maleimide groups on MB surfaces. MB reacted with scVEGF and led to the conjugation of 1.2 × 105 molecules scVEGF per MB. Functional adhesion of sc-VEGF-MB was shown in parallel plate flow chamber assays. At a shear stress of 1.0 dynes/cm2, scVEGF-MB exhibited 5-fold higher adhesion to both recombinant VEGFR-2 substrates and VEGFR-2-expressing endothelial cells compared with nontargeted control MB. Additionally, scVEGF-MB targeted to immobilized VEGFR-2 in an ultrasound flow phantom showed an 8-fold increase in mean acoustic signal relative to casein-coated control channels. In an in vivo model of tumor angiogenesis, scVEGF MB showed

  17. Formation of nets of corner-shared bicapped gold squares in SrAu3Ge: how a BaAl4-type derivative reconciles fewer valence electrons and the origin of its uniaxial negative thermal expansion.

    PubMed

    Lin, Qisheng; Corbett, John D

    2012-03-14

    SrAu(3)Ge was synthesized by direct fusion of the mixed elements at high temperature followed by annealing treatments, and its structure was determined by single crystal X-ray diffraction means in space group (Pearson symbol: tP10) P4/nmm, a = 6.264(1) Å, c = 5.5082(9) Å, Z = 2 at room temperature. The structure of SrAu(3)Ge, a reapportioned √2 × √2 × 1 superstructure of CeMg(2)Si(2) (P4/mmm), exhibits checkerboard nets of corner-shared bicapped Au squares (or corner-shared Au(Au(4/2))Ge octahedra), in which the apical Au-Ge pairs in adjoining nets are strongly interbonded in the c direction. This motif contrasts with that of the common BaAl(4) (I4/mmm) prototype in which Al squares in comparable layers are alternately monocapped by Al from the top or the bottom. Typical examples show valence electron counts (vec) between 12 and 16 for the BaAl(4) type and that for CeMg(2)Si(2) is similar, 15. The special stability of SrAu3Ge, with vec = 9, derives from significant relativistic contribution of the Au 5d(10) states to the Au-Ge and Au-Au bonding. These factors are also recognized in the marked redistribution of Au and Ge site occupancies from those in CeMg(2)Si(2). SrAu(3)Ge exhibits a pronounced uniaxial negative thermal expansion along c, with a coefficient of -1.57 versus 2.16 × 10(-5) K(-1) in a and b. The reticulated Au(5)Ge octahedral layers expand in the ab plane on heating, whereas the strong, interlayer Au-Ge bonds remain fixed.

  18. Novel live imaging techniques of cellular functions and in vivo tumors based on precise design of small molecule-based 'activatable' fluorescence probes.

    PubMed

    Urano, Yasuteru

    2012-12-01

    Recently established rational design strategies for novel fluorescence probes, especially those based on photoinduced electron transfer and spirocyclization were reviewed. Based on these design strategies, various novel fluorescence probes were successfully developed including those for reactive oxygen species, reporter enzymes. Furthermore, in vivo cancer imaging techniques based on rationally designed activatable probes such as cancer-specific antibodies tagged with acidic-pH activatable fluorescence probes and peptidase activatable fluorescence probes were also discussed.

  19. Screening for RB1 mutations in tumor tissue using denaturing high performance liquid chromatography, multiplex ligation-dependent probe amplification, and loss of heterozygosity analysis.

    PubMed

    Sellner, Loryn N; Edkins, Edward; Smith, Nicholas

    2006-01-01

    Retinoblastoma is a malignant retinal neoplasm arising in infancy as a result of inactivating mutations in both alleles of the retinoblastoma susceptibility gene, RB1. Identification of the causative RB1 mutations in a patient assists in the clinical management of the affected patient and risk assessment of family members, principally on the basis of whether there is a germline mutation. In this paper, we describe our experience with molecular analysis of RB1 mutations in tumor and nontumor samples from 18 retinoblastoma patients, using multiplex ligation dependent probe amplification (MLPA) to detect large deletions or duplications, microsatellite analysis to detect loss of heterozygosity (LOH), and denaturing high performance liquid chromatography (D-HPLC) analysis to detect point mutations and small insertions or deletions. We found LOH in 71% of all cases, and 83% of these were due to acquired isodisomy rather than chromosomal deletions. Small mutations identified by D-HPLC accounted for 78% of the non-LOH mutations, and large deletions/duplications detected by MLPA accounted for the remaining 22%. We give the first report of a large, multiexon duplication in RB1 of exons 8 to 18. PMID:16808635

  20. Detection of MDM2/CDK4 amplification in lipomatous soft tissue tumors from formalin-fixed, paraffin-embedded tissue: comparison of multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH).

    PubMed

    Creytens, David; van Gorp, Joost; Ferdinande, Liesbeth; Speel, Ernst-Jan; Libbrecht, Louis

    2015-02-01

    In this study, the detection of MDM2 and CDK4 amplification was evaluated in lipomatous soft tissue tumors using multiplex ligation-dependent probe amplification (MLPA), a PCR-based technique, in comparison with fluorescence in situ hybridization (FISH). These 2 techniques were evaluated in a series of 77 formalin-fixed, paraffin-embedded lipomatous tumors (27 benign adipose tumors, 28 atypical lipomatous tumors/well-differentiated liposarcomas, 18 dedifferentiated liposarcomas, and 4 pleomorphic liposarcomas). Using MLPA, with a cut-off ratio of >2, 36/71 samples (22 atypical lipomatous tumors/well-differentiated liposarcomas, and 14 dedifferentiated liposarcomas) showed MDM2 and CDK4 amplification. Using FISH as gold standard, MLPA showed a sensitivity of 90% (36/40) and a specificity of 100% (31/31) in detecting amplification of MDM2 and CDK4 in lipomatous soft tissue tumors. In case of high-level amplification (MDM2-CDK4/CEP12 ratio >5), concordance was 100%. Four cases of atypical lipomatous tumor/well-differentiated liposarcoma (4/26, 15%) with a low MDM2 and CDK4 amplification level (MDM2-CDK4/CEP12 ratio ranging between 2 and 2.5) detected by FISH showed no amplification by MLPA, although gain of MDM2 and CDK4 (ratios ranging between 1.6 and 1.9) was seen with MLPA. No amplification was detected in benign lipomatous tumors and pleomorphic liposarcomas. Furthermore, there was a very high concordance between the ratios obtained by FISH and MLPA. In conclusion, MLPA proves to be an appropriate and straightforward technique for screening MDM2/CDK4 amplification in lipomatous tumors, especially when a correct cut-off value and reference samples are chosen, and could be considered a good alternative to FISH to determine MDM2 and CDK4 amplification in liposarcomas. Moreover, because MLPA, as a multiplex technique, allows simultaneous detection of multiple chromosomal changes of interest, it could be in the future a very reliable and fast molecular analysis on

  1. Preclinical Evaluation of a Potential GSH Ester Based PET/SPECT Imaging Probe DT(GSHMe)2 to Detect Gamma Glutamyl Transferase Over Expressing Tumors

    PubMed Central

    Khurana, Harleen; Meena, Virendra Kumar; Prakash, Surbhi; Chuttani, Krishna; Chadha, Nidhi; Jaswal, Ambika; Dhawan, Devinder Kumar; Mishra, Anil Kumar; Hazari, Puja Panwar

    2015-01-01

    Gamma Glutamyl Transferase (GGT) is an important biomarker in malignant cancers. The redox processes ensuing from GGT-mediated metabolism of extracellular GSH are implicated in critical aspects of tumor cell biology. Reportedly, Glutathione monoethyl ester (GSHMe) is a substrate of GGT, which has been used for its rapid transport over glutathione. Exploring GGT to be an important target, a homobivalent peptide system, DT(GSHMe)2 was designed to target GGT-over expressing tumors for diagnostic purposes. DT(GSHMe)2 was synthesized, characterized and preclinically evaluated in vitro using toxicity, cell binding assays and time dependent experiments. Stable and defined radiochemistry with 99mTc and 68Ga was optimized for high radiochemical yield. In vivo biodistribution studies were conducted for different time points along with scintigraphic studies of radiolabeled DT(GSHMe)2 on xenografted tumor models. For further validation, in silico docking studies were performed on GGT (hGGT1, P19440). Preclinical in vitro evaluations on cell lines suggested minimal toxicity of DT(GSHMe)2 at 100 μM concentration. Kinetic analysis revealed transport of 99mTc-DT(GSHMe)2 occurs via a saturable high-affinity carrier with Michaelis constant (Km) of 2.25 μM and maximal transport rate velocity (Vmax) of 0.478 μM/min. Quantitative estimation of GGT expression from western blot experiments showed substantial expression with 41.6 ± 7.07 % IDV for tumor. Small animal micro PET (Positron Emission Tomography)/CT(Computed Tomography) coregistered images depicted significantly high uptake of DT(GSHMe)2 at the BMG-1 tumor site. ROI analysis showed high tumor to contra lateral muscle ratio of 9.33 in PET imaging studies. Avid accumulation of radiotracer was observed at tumor versus inflammation site at 2 h post i.v. injection in an Ehrlich Ascites tumor (EAT) mice model, showing evident specificity for tumor. We propose DT(GSHMe)2 to be an excellent candidate for prognostication and tumor

  2. Probing tumor-stroma interactions and response to photodynamic therapy in a 3D pancreatic cancer-fibroblast co-culture model

    NASA Astrophysics Data System (ADS)

    Glidden, Michael D.; Massodi, Iqbal; Rizvi, Imran; Celli, Jonathan P.; Hasan, Tayyaba

    2012-02-01

    Pancreatic ductal adenocarcinoma is a lethal disease that is often unresectable by the time of diagnosis and is typically non-responsive to chemo- and radiotherapy, resulting in a five year survival of only 3%. Tumors of the pancreas are characterized by a dense fibrous stroma rich in extracellular matrix proteins, which is implicated in poor therapeutic response, though its precise roles remain poorly understood. Indeed, while the use of therapeutics that target the stroma is an emerging paradigm in the clinical management of this disease, the primary focus of such efforts is to enhance drug penetration through dense fibrous stroma and it is unclear to what extent the characteristically rigid stroma of pancreatic tumors imparts drug resistance by acting as a complex signaling partner, or merely as a physical barrier for drug delivery. Here we use 3D in vitro co-cultures of pancreatic cancer cells and normal human fibroblasts as a model system to study heterotypic interactions between these populations. Leveraging this in vitro model along with image-based methods for quantification of growth and therapeutic endpoints, we characterize these co-cultures and examine the role of verteporfin-based photodynamic therapy (PDT) for targeting tumor-fibroblast interactions in pancreatic tumors.

  3. Probing single-tumor cell interactions with different-age type I collagen networks by synchrotron-based Fourier transform infrared microspectroscopy.

    PubMed

    Guilbert, Marie; Eklouh-Molinier, Christophe; Wehbe, Katia; Sulé-Suso, Josep; Yang, Ying; Cinque, Gianfelice; Jeannesson, Pierre; Sockalingum, Ganesh D

    2014-01-01

    We report here on a first study using synchrotron radiation-based Fourier transform infrared microspectroscopy and imaging to investigate HT1080 human fibrosarcoma cells grown onto different-aged type I collagen networks. Spectral images were analyzed with k-means and fuzzy C-means (FCM) clustering algorithms. K-means delineated tumor cells from their surrounding collagen networks and the latter as a function of age mainly due to specific changes in the sugar absorption region. The FCM analysis gave a better nuance of the spectral images. A progression of the biochemical information was observed upon going from the cellular compartments to the pericellular contact regions and to the intact collagens of the different age groups. Two spectral markers based on sugar and protein bands via the intensity ratio (I1032/I1655) and band area ratio (Asugar/Aamide II), showed an increase in advanced glycation endproducts (AGEs) with age. A clear-separation of the three age groups was obtained for spectra originating from the peripheral contact areas mainly due to changes in protein band intensities. The above-described markers decreased to constant levels for the three conditions indicating a masking of the biochemical information. These results hold promises to better understand the impact of age on tumor progression processes while highlighting new markers of the tumor cell invasion front. PMID:25193972

  4. Spectrophotometric probe

    DOEpatents

    Prather, William S.; O'Rourke, Patrick E.

    1994-01-01

    A support structure bearing at least one probe for making spectrophotometric measurements of a fluid using a source of light and a spectrophotometer. The probe includes a housing with two optical fibers and a planoconvex lens. A sleeve bearing a mirror surrounds the housing. The lens is separated from the mirror by a fixed distance, defining an interior space for receiving a volume of the fluid sample. A plurality of throughholes extending through the sleeve communicate between the sample volume and the exterior of the probe, all but one hole bearing a screen. A protective jacket surrounds the probe. A hollow conduit bearing a tube is formed in the wall of the probe for venting any air in the interior space when fluid enters. The probe is held at an acute angle so the optic fibers carrying the light to and from the probe are not bent severely on emergence from the probe.

  5. Spectrophotometric probe

    DOEpatents

    Prather, W.S.; O'Rourke, P.E.

    1994-08-02

    A support structure is described bearing at least one probe for making spectrophotometric measurements of a fluid using a source of light and a spectrophotometer. The probe includes a housing with two optical fibers and a planoconvex lens. A sleeve bearing a mirror surrounds the housing. The lens is separated from the mirror by a fixed distance, defining an interior space for receiving a volume of the fluid sample. A plurality of throughholes extending through the sleeve communicate between the sample volume and the exterior of the probe, all but one hole bearing a screen. A protective jacket surrounds the probe. A hollow conduit bearing a tube is formed in the wall of the probe for venting any air in the interior space when fluid enters. The probe is held at an acute angle so the optic fibers carrying the light to and from the probe are not bent severely on emergence from the probe. 3 figs.

  6. NASA SMART Probe: Breast Cancer Application

    NASA Technical Reports Server (NTRS)

    Mah, Robert W.; Norvig, Peter (Technical Monitor)

    2000-01-01

    There is evidence in breast cancer and other malignancies that the physiologic environment within a tumor correlates with clinical outcome. We are developing a unique percutaneous Smart Probe to be used at the time of needle biopsy of the breast. The Smart Probe will simultaneously measure multiple physiologic parameters within a breast tumor. Direct and indirect measurements of tissue oxygen levels, blood flow, pH, and tissue fluid pressure will be analyzed in real-time. These parameters will be interpreted individually and collectively by innovative neural network techniques using advanced intelligent software. The goals are 1) develop a pecutaneous Smart Probe with multiple sensor modalities and applying advanced Information Technologies to provide real time diagnostic information of the tissue at tip of the probe, 2) test the percutaneous Smart Probe in women with benign and malignant breast masses who will be undergoing surgical biopsy, 3) correlate probe sensor data with benign and malignant status of breast masses, 4) determine whether the probe can detect physiologic differences within a breast tumor, and its margins, and in adjacent normal breast tissue, 5) correlate probe sensor data with known prognostic factors for breast caner, including tumor size, tumor grade, axillary lymph node metastases, estrogen receptor and progesterone receptor status.

  7. Multifunctional imaging probe based on gadofulleride nanoplatform

    NASA Astrophysics Data System (ADS)

    Zheng, Jun-Peng; Liu, Qiao-Ling; Zhen, Ming-Ming; Jiang, Feng; Shu, Chun-Ying; Jin, Chan; Yang, Yongji; Alhadlaq, Hisham A.; Wang, Chun-Ru

    2012-05-01

    A FAR over-expressed tumor targeting multifunctional imaging probe has been fabricated based on gadofulleride nanoplatform. The combination of highly efficient MRI contrast enhancement and sensitive fluorescence imaging along with the preferential uptake toward FAR tumor cells suggest that the obtained multifunctional imaging probe possesses complementary capabilities for anatomical resolution and detection sensitivity.A FAR over-expressed tumor targeting multifunctional imaging probe has been fabricated based on gadofulleride nanoplatform. The combination of highly efficient MRI contrast enhancement and sensitive fluorescence imaging along with the preferential uptake toward FAR tumor cells suggest that the obtained multifunctional imaging probe possesses complementary capabilities for anatomical resolution and detection sensitivity. Electronic supplementary information (ESI) available: Materials, instruments and methods, synthesis details, XPS characterization for estimation of average molecular formula, evaluation of conjugated FA and FITC ratio, zeta potential and fluorescent images. See DOI: 10.1039/c2nr30836c

  8. The cluster compound In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} containing Mo{sub 14} clusters and the new mono- and bi-capped trioctahedral Mo{sub 15} and Mo{sub 16} clusters: Synthesis, crystal structure, and electrical and magnetic properties

    SciTech Connect

    Gall, Philippe; Guizouarn, Thierry; Gougeon, Patrick

    2015-07-15

    Single crystals of the new quaternary compound In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} were obtained by solid state reaction. The crystal structure was determined by single-crystal X-ray diffraction. In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} crystallizes in the orthorhombic space group Pbca with unit-cell parameters a=9.4432(14) Å, b=11.4828(12) Å, c=20.299(4) Å and Z=4. Full-matrix least-squares refinement on F{sup 2} using 3807 independent reflections for 219 refinable parameters resulted in R{sub 1}=0.0259 and wR{sub 2}=0.0591. The crystal structure contains in addition to Mo{sub 14} clusters the first examples of mono- and bi-capped trioctahedral Mo{sub 14} i.e. Mo{sub 15} and Mo{sub 16} clusters. The oxygen framework derives from a stacking along the a direction of close-packed layers with sequence (…ABAC…). The Mo–Mo distances range between 2.6938(5) and 2.8420(6) Å and the Mo–O distances between 1.879(5) and 2.250(3) Å, as usually observed in molybdenum oxide clusters. The indium atoms form In{sub 4}{sup 6+} bent chains with In–In distances of 2.6682(5) and 2.6622(8) Å and the Ti atoms are in highly distorted octahedral sites of oxygen atoms with Ti–O distances ranging between 1.865(4) and 2.161(4) Å. Magnetic susceptibility measurements confirm the presence of Ti{sup 4+} cations and the absence of localized moments on the Mo network. Electrical resistivity measurements on a single crystal of In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} show a semimetallic behavior. - Graphical abstract: We present here the synthesis, the crystal structure, and the electrical and magnetic properties of the new compound In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} in which Mo{sub 14} clusters coexist statistically with mono- and bi-capped trioctahedral Mo{sub 14} that is Mo{sub 15} and Mo{sub 16} clusters. - Highlights: • Single crystals of In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} were obtained by solid state

  9. Optical probe

    DOEpatents

    Hencken, Kenneth; Flower, William L.

    1999-01-01

    A compact optical probe is disclosed particularly useful for analysis of emissions in industrial environments. The instant invention provides a geometry for optically-based measurements that allows all optical components (source, detector, rely optics, etc.) to be located in proximity to one another. The geometry of the probe disclosed herein provides a means for making optical measurements in environments where it is difficult and/or expensive to gain access to the vicinity of a flow stream to be measured. Significantly, the lens geometry of the optical probe allows the analysis location within a flow stream being monitored to be moved while maintaining optical alignment of all components even when the optical probe is focused on a plurality of different analysis points within the flow stream.

  10. Sinus Tumors

    MedlinePlus

    ... Tumors Nasal Deformities Choanal Atresia Epiphora (Excessive Tearing) Disclosure Statement Printer Friendly Sinus Tumors Abtin Tabaee, MD Introduction Tumors of the nose and paranasal sinuses are rare, accounting for fewer than 1% of all tumors. These ...

  11. Conductivity Probe

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Thermal and Electrical Conductivity Probe (TECP) for NASA's Phoenix Mars Lander took measurements in Martian soil and in the air.

    The needles on the end of the instrument were inserted into the Martian soil, allowing TECP to measure the propagation of both thermal and electrical energy. TECP also measured the humidity in the surrounding air.

    The needles on the probe are 15 millimeters (0.6 inch) long.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  12. NASA Smart Surgical Probe Project

    NASA Technical Reports Server (NTRS)

    Mah, Robert W.; Andrews, Russell J.; Jeffrey, Stefanie S.; Guerrero, Michael; Papasin, Richard; Koga, Dennis (Technical Monitor)

    2002-01-01

    Information Technologies being developed by NASA to assist astronaut-physician in responding to medical emergencies during long space flights are being employed for the improvement of women's health in the form of "smart surgical probe". This technology, initially developed for neurosurgery applications, not only has enormous potential for the diagnosis and treatment of breast cancer, but broad applicability to a wide range of medical challenges. For the breast cancer application, the smart surgical probe is being designed to "see" a suspicious lump, determine by its features if it is cancerous, and ultimately predict how the disease may progress. A revolutionary early breast cancer detection tool based on this technology has been developed by a commercial company and is being tested in human clinical trials at the University of California at Davis, School of Medicine. The smart surgical probe technology makes use of adaptive intelligent software (hybrid neural networks/fuzzy logic algorithms) with the most advanced physiologic sensors to provide real-time in vivo tissue characterization for the detection, diagnosis and treatment of tumors, including determination of tumor microenvironment and evaluation of tumor margins. The software solutions and tools from these medical applications will lead to the development of better real-time minimally-invasive smart surgical probes for emergency medical care and treatment of astronauts on long space flights.

  13. A new ODE tumor growth modeling based on tumor population dynamics

    SciTech Connect

    Oroji, Amin; Omar, Mohd bin; Yarahmadian, Shantia

    2015-10-22

    In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan.

  14. Pollution Probe.

    ERIC Educational Resources Information Center

    Chant, Donald A.

    This book is written as a statement of concern about pollution by members of Pollution Probe, a citizens' anti-pollution group in Canada. Its purpose is to create public awareness and pressure for the eventual solution to pollution problems. The need for effective government policies to control the population explosion, conserve natural resources,…

  15. Spinal tumor

    MedlinePlus

    Tumor - spinal cord ... spinal tumors occur in the nerves of the spinal cord itself. Most often these are ependymomas and other ... gene mutations. Spinal tumors can occur: Inside the spinal cord (intramedullary) In the membranes (meninges) covering the spinal ...

  16. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  17. Tumor Types

    MedlinePlus

    ... acoustic neuroma is also known as a schwannoma, vestibular schwannoma, or neurilemmoma. Characteristics Arises from cells that ... multiple CNS tumors, including neurofibromas, multiple meningiomas, bilateral vestibular schwannomas, optic nerve gliomas, and spinal cord tumors. ...

  18. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  19. Urogenital tumors

    SciTech Connect

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  20. Hydrodynamic ultrasonic probe

    DOEpatents

    Day, Robert A.; Conti, Armond E.

    1980-01-01

    An improved probe for in-service ultrasonic inspection of long lengths of a workpiece, such as small diameter tubing from the interior. The improved probe utilizes a conventional transducer or transducers configured to inspect the tubing for flaws and/or wall thickness variations. The probe utilizes a hydraulic technique, in place of the conventional mechanical guides or bushings, which allows the probe to move rectilinearly or rotationally while preventing cocking thereof in the tube and provides damping vibration of the probe. The probe thus has lower friction and higher inspection speed than presently known probes.

  1. Targeting the expression of integrin receptors in tumors

    NASA Astrophysics Data System (ADS)

    Bloch, Sharon; Liang, Kexian; Dorshow, Richard B.; Ye, Yunpeng; Achilefu, Samuel I.

    2004-06-01

    Expression of integrin αvβ3 is upregulated in a number of cancers including colon, pancreas, lung and breast. Additionally, αvβ3 integrin expression has been linked to tumor metastasis and targeting this cell surface protein could provide a viable approach to image and evaluate the metastatic potential of tumors. Accordingly, we evaluated the selective retention of some near infrared (NIR) fluorescent probes in nude mice bearing A549 lung cancer xenograft that express αvβ3 integrin. Our preliminary results indicate that a novel NIR probe designed to target this integrin selectively accumulated in A549 tumor while other non-integrin specific probes were not retained in the tumor. Blocking studies show that tumor uptake of the probe is mediated by αvβ3 integrin receptor.

  2. Pindborg tumor

    PubMed Central

    Caliaperoumal, Santhosh Kumar; Gowri, S.; Dinakar, J.

    2016-01-01

    Calcifying epithelial odontogenic tumor (CEOT), also known as Pindborg tumor, is a rare odontogenic epithelial neoplasm. So far, nearly 200 cases have been reported in the literature. We are reporting a case of CEOT in a 42-year-old male patient with painless bony swelling in the mandible. The clinical, radiographic, and histopathologic features are discussed with relevant references. PMID:27041911

  3. Hypothalamic tumor

    MedlinePlus

    ... occur at any age. They are often more aggressive in adults than in children. In adults, tumors ... The treatment depends on how aggressive the tumor is, and whether it is a glioma or another type of cancer. Treatment may involve combinations of surgery, radiation , ...

  4. Pituitary Tumors

    MedlinePlus

    ... pituitary is the "master control gland" - it makes hormones that affect growth and the functions of other glands in the body. Pituitary tumors are common, but often they don't cause health ... tumor produces hormones and disrupts the balance of hormones in your ...

  5. Dr. Harry Whelan With the Light Emitting Diode Probe

    NASA Technical Reports Server (NTRS)

    1999-01-01

    The red light from the Light Emitting Diode (LED) probe shines through the fingers of Dr. Harry Whelan, a pediatric neurologist at the Children's Hospital of Wisconsin in Milwaukee. Dr. Whelan uses the long waves of light from the LED surgical probe to activate special drugs that kill brain tumors. Laser light previously has been used for this type of surgery, but the LED light illuminates through all nearby tissues, reaching parts of tumors that shorter wavelengths of laser light carnot. The new probe is safer because the longer wavelengths of light are cooler than the shorter wavelengths of laser light, making the LED less likely to injure normal brain tissue near the tumor. Also, it can be used for hours at a time while still remaining cool to the touch. The probe was developed for photodynamic cancer therapy under a NASA Small Business Innovative Research Program grant. The program is part of NASA's Technology Transfer Department at the Marshall Space Flight Center.

  6. Imaging tumor hypoxia by near-infrared fluorescence tomography

    NASA Astrophysics Data System (ADS)

    Biswal, Nrusingh C.; Pavlik, Christopher; Smith, Michael B.; Aguirre, Andres; Xu, Yan; Zanganeh, Saeid; Kuhn, Liisa T.; Claffey, Kevin P.; Zhu, Quing

    2011-06-01

    We have developed a novel nitroimidazole indocyanine dye conjugate for tumor-targeted hypoxia fluorescence tomography. The hypoxia probe has been evaluated in vitro using tumor cell lines and in vivo with tumor targeting in mice. The in vitro cell studies were performed to assess fluorescence labeling differences between hypoxia and normoxia conditions. When treated with the hypoxia probe, a fluorescence emission ratio of 2.5-fold was found between the cells incubated under hypoxia compared to the cells in normoxia condition. Hypoxia specificity was also confirmed by comparing the cells treated with indocyanine dye alone. In vivo tumor targeting in mice showed that the fluorescence signals measured at the tumor site were twice those at the normal site after 150 min post-injection of the hypoxia probe. On the other hand, the fluorescence signals measured after injection of indocyanine dye were the same at tumor and normal sites. In vivo fluorescence tomography images of mice injected with the hypoxia probe showed that the probe remained for more than 5 to 7 h in the tumors, however, the images of mice injected with indocyanine only dye confirmed that the unbound dye washed out in less than 3 h. These findings are supported with fluorescence images of histological sections of tumor samples using a Li-COR scanner and immunohistochemistry technique for tumor hypoxia.

  7. Luminescent probes for optical in vivo imaging

    NASA Astrophysics Data System (ADS)

    Texier, Isabelle; Josserand, Veronique; Garanger, Elisabeth; Razkin, Jesus; Jin, Zhaohui; Dumy, Pascal; Favrot, Marie; Boturyn, Didier; Coll, Jean-Luc

    2005-04-01

    Going along with instrumental development for small animal fluorescence in vivo imaging, we are developing molecular fluorescent probes, especially for tumor targeting. Several criteria have to be taken into account for the optimization of the luminescent label. It should be adapted to the in vivo imaging optical conditions : red-shifted absorption and emission, limited overlap between absorption and emission for a good signal filtering, optimized luminescence quantum yield, limited photo-bleaching. Moreover, the whole probe should fulfill the biological requirements for in vivo labeling : adapted blood-time circulation, biological conditions compatibility, low toxicity. We here demonstrate the ability of the imaging fluorescence set-up developed in LETI to image the bio-distribution of molecular probes on short times after injection. Targeting with Cy5 labeled holo-transferrin of subcutaneous TS/Apc (angiogenic murine breast carcinoma model) or IGROV1 (human ovarian cancer) tumors was achieved. Differences in the kinetics of the protein uptake by the tumors were evidenced. IGROV1 internal metastatic nodes implanted in the peritoneal cavity could be detected in nude mice. However, targeted metastatic nodes in lung cancer could only be imaged after dissection of the mouse. These results validate our fluorescence imaging set-up and the use of Cy5 as a luminescent label. New fluorescent probes based on this dye and a molecular delivery template (the RAFT molecule) can thus be envisioned.

  8. [Adipocytic tumors].

    PubMed

    Stock, Nathalie

    2015-01-01

    Adipocytic tumors are the most common mesenchymal neoplasms, liposarcoma accounting for approximately 20% of soft tissue sarcomas. The differential diagnosis between benign and malignant tumors is often problematic and represents a significant proportion of consultation cases. The goal of this article is to review liposarcoma subtypes, the main benign adipocytic neoplasms: lipoblastoma, hibernoma, spindle/pleomorphic cell lipoma, chondroid lipoma, as well as non adipocytic neoplasms with a lipomatous component such as lipomatous solitary fibrous tumor, emphasizing on practical differential diagnosis issues, and immunohistochemical and molecular tools allowing their resolution.

  9. Monoclonals and DNA probes in diagnostic and preventative medicine

    SciTech Connect

    Gallo, R.C.; Della Povta, G.; Albertini, A.

    1987-01-01

    This book contains 24 selections. Some of the titles are: Use of DNA Probes for Prenatal and Carrier Diagnosis of Hemophilia and Fragile X Mental Retardation; The Application of DNA Probes to Diagnosis and Research of Duchenne Muscular Dystrophy: Clinical Trial, New Probes and Deletion Mapping; Molecular Genetics of the Human Collagens; Molecular Genetics of Human Steroid 21-Hydroxylase Genes; Detection of Hepatitis B Virus DNA and Hepatitis Delta Virus RNA: Implications in Diagnosis and Pathogenesis; and DNA Probes to Evaluate the Possible Association of Papovaviruses with Human Tumors.

  10. Wilms Tumor

    MedlinePlus

    ... diagnosis, and the condition, or histology , of the cancer cells when observed under a microscope. "Favorable" histology is associated with a good chance of a cure; tumors with "unfavorable" histology are more aggressive and ...

  11. Tumor Markers

    MedlinePlus

    ... types: Germ cell tumors, lymphoma, leukemia, melanoma, and neuroblastoma Tissue analyzed: Blood How used: To assess stage, ... NSE) Cancer types: Small cell lung cancer and neuroblastoma Tissue analyzed: Blood How used: To help in ...

  12. Retrorectal tumors.

    PubMed

    Bullard Dunn, Kelli

    2010-02-01

    Retrorectal or presacral tumors are rare and can be challenging to diagnose and treat. Because the retrorectal space contains multiple embryologic remnants derived from various tissues, the tumors that develop in this space are heterogeneous. Most lesions are benign, but malignant neoplasms are not uncommon. Lesions are classified as congenital, neurogenic, osseous, inflammatory, or miscellaneous. Although treatment depends on diagnosis and anatomic location, most retrorectal lesions will require surgical resection.

  13. The immunological identity of tumor

    PubMed Central

    Miska, Jason; Devarajan, Priyadharshini; Chen, Zhibin

    2013-01-01

    By means of well-characterized autoimmunity models, we comparatively probed the “selfness” of malignant cells and their normal counterparts. We found that tumors activate self-tolerance mechanisms much more efficiently than normal tissues, reflecting a status of immunoprivileged “self.” Our findings indicate that potent autoimmune responses can eradicate established malignancies, yet the collateral destruction of healthy tissues may prove difficult to circumvent. PMID:23734327

  14. Targeting tumor acidity

    NASA Astrophysics Data System (ADS)

    Reshetnyak, Yana K.; Engelman, Donald M.; Andreev, Oleg A.

    2012-02-01

    One of the main features of solid tumors is extracellular acidity, which correlates with tumor aggressiveness and metastatic potential. We introduced novel approach in targeting of acidic tumors, and translocation of cell-impermeable cargo molecules across cellular membrane. Our approach is based on main principle of insertion and folding of a polypeptide in lipid bilayer of membrane. We have identified family of pH Low Insertion Peptides (pHLIPs), which are capable spontaneous insertion and folding in membrane at mild acidic conditions. The affinity of peptides of pHLIP family to membrane at low pH is several times higher than at neutral pH. The process of peptides folding occurs within milliseconds. The energy released in a result of folding (about 2 kcal/mol) could be used to move polar cargo across a membrane, which is a novel concept in drug delivery. pHLIP peptides could be considered as a pH-sensitive single peptide molecular transporters and conjugated with imaging probes for fluorescence, MR, PET and SPECT imaging, they represent a novel in vivo marker of acidity. The work is supported by NIH grants CA133890 and GM073857 to OAA, DME, YRK.

  15. Galileo Probe Battery System

    NASA Technical Reports Server (NTRS)

    Dagarin, B. P.; Taenaka, R. K.; Stofel, E. J.

    1997-01-01

    The conclusions of the Galileo probe battery system are: the battery performance met mission requirements with margin; extensive ground-based and flight tests of batteries prior to probe separation from orbiter provided good prediction of actual entry performance at Jupiter; and the Li-SO2 battery was an important choice for the probe's main power.

  16. Ultrafast scanning probe microscopy

    DOEpatents

    Weiss, Shimon; Chemla, Daniel S.; Ogletree, D. Frank; Botkin, David

    1995-01-01

    An ultrafast scanning probe microscopy method for achieving subpicosecond-temporal resolution and submicron-spatial resolution of an observation sample. In one embodiment of the present claimed invention, a single short optical pulse is generated and is split into first and second pulses. One of the pulses is delayed using variable time delay means. The first pulse is then directed at an observation sample located proximate to the probe of a scanning probe microscope. The scanning probe microscope produces probe-sample signals indicative of the response of the probe to characteristics of the sample. The second pulse is used to modulate the probe of the scanning probe microscope. The time delay between the first and second pulses is then varied. The probe-sample response signal is recorded at each of the various time delays created between the first and second pulses. The probe-sample response signal is then plotted as a function of time delay to produce a cross-correlation of the probe sample response. In so doing, the present invention provides simultaneous subpicosecond-temporal resolution and submicron-spatial resolution of the sample.

  17. Ultrafast scanning probe microscopy

    DOEpatents

    Weiss, S.; Chemla, D.S.; Ogletree, D.F.; Botkin, D.

    1995-05-16

    An ultrafast scanning probe microscopy method is described for achieving subpicosecond-temporal resolution and submicron-spatial resolution of an observation sample. In one embodiment of the present claimed invention, a single short optical pulse is generated and is split into first and second pulses. One of the pulses is delayed using variable time delay means. The first pulse is then directed at an observation sample located proximate to the probe of a scanning probe microscope. The scanning probe microscope produces probe-sample signals indicative of the response of the probe to characteristics of the sample. The second pulse is used to modulate the probe of the scanning probe microscope. The time delay between the first and second pulses is then varied. The probe-sample response signal is recorded at each of the various time delays created between the first and second pulses. The probe-sample response signal is then plotted as a function of time delay to produce a cross-correlation of the probe sample response. In so doing, the present invention provides simultaneous subpicosecond-temporal resolution and submicron-spatial resolution of the sample. 6 Figs.

  18. Traversing probe system

    DOEpatents

    Mashburn, Douglas N.; Stevens, Richard H.; Woodall, Harold C.

    1977-01-01

    This invention comprises a rotatable annular probe-positioner which carries at least one radially disposed sensing probe, such as a Pitot tube having a right-angled tip. The positioner can be coaxially and rotatably mounted within a compressor casing or the like and then actuated to orient the sensing probe as required to make measurements at selected stations in the annulus between the positioner and compressor casing. The positioner can be actuated to (a) selectively move the probe along its own axis, (b) adjust the yaw angle of the right-angled probe tip, and (c) revolve the probe about the axis common to the positioner and casing. A cam plate engages a cam-follower portion of the probe and normally rotates with the positioner. The positioner includes a first-motor-driven ring gear which effects slidable movement of the probe by rotating the positioner at a time when an external pneumatic cylinder is actuated to engage the cam plate and hold it stationary. When the pneumatic cylinder is not actuated, this ring gear can be driven to revolve the positioner and thus the probe to a desired circumferential location about the above-mentioned common axis. A second motor-driven ring gear included in the positioner can be driven to rotate the probe about its axis, thus adjusting the yaw angle of the probe tip. The positioner can be used in highly corrosive atmosphere, such as gaseous uranium hexafluoride.

  19. Electrical resistivity probes

    DOEpatents

    Lee, Ki Ha; Becker, Alex; Faybishenko, Boris A.; Solbau, Ray D.

    2003-10-21

    A miniaturized electrical resistivity (ER) probe based on a known current-voltage (I-V) electrode structure, the Wenner array, is designed for local (point) measurement. A pair of voltage measuring electrodes are positioned between a pair of current carrying electrodes. The electrodes are typically about 1 cm long, separated by 1 cm, so the probe is only about 1 inch long. The electrodes are mounted to a rigid tube with electrical wires in the tube and a sand bag may be placed around the electrodes to protect the electrodes. The probes can be positioned in a borehole or on the surface. The electrodes make contact with the surrounding medium. In a dual mode system, individual probes of a plurality of spaced probes can be used to measure local resistance, i.e. point measurements, but the system can select different probes to make interval measurements between probes and between boreholes.

  20. The NASA Smart Probe Project for real-time multiple microsensor tissue recognition

    NASA Technical Reports Server (NTRS)

    Andrews, Russell J.; Mah, Robert W.

    2003-01-01

    BACKGROUND: Remote surgery requires automated sensors, effectors and sensor-effector communication. The NASA Smart Probe Project has focused on the sensor aspect. METHODS: The NASA Smart Probe uses neural networks and data from multiple microsensors for a unique tissue signature in real time. Animal and human trials use several probe configurations: (1) 8-microsensor probe (2.5 mm in diameter) for rodent studies (normal and subcutaneous mammary tumor tissues), and (2) 21-gauge needle probe with 3 spectroscopic fibers and an impedance microelectrode for breast cancer diagnosis in humans. Multisensor data are collected in real time (update 100 times/s) using PCs. RESULTS: Human data (collected by NASA licensee BioLuminate) from 15 women undergoing breast biopsy distinguished normal tissue from both benign tumors and breast carcinoma. Tumor margins and necrosis are rapidly detected. CONCLUSION: Real-time tissue identification is achievable. Potential applications, including probes incorporating nanoelectrode arrays, are presented. Copyright 2003 S. Karger AG, Basel.

  1. Investigation of a MMP-2 Activity-Dependent Anchoring Probe for Nuclear Imaging of Cancer

    PubMed Central

    Temma, Takashi; Hanaoka, Hirofumi; Yonezawa, Aki; Kondo, Naoya; Sano, Kohei; Sakamoto, Takeharu; Seiki, Motoharu; Ono, Masahiro; Saji, Hideo

    2014-01-01

    Purpose Since matrix metalloproteinase-2 (MMP-2) is an important marker of tumor malignancy, we developed an original drug design strategy, MMP-2 activity dependent anchoring probes (MDAP), for use in MMP-2 activity imaging, and evaluated the usefulness of this probe in in vitro and in vivo experiments. Methods We designed and synthesized MDAP1000, MDAP3000, and MDAP5000, which consist of 4 independent moieties: RI unit (111In hydrophilic chelate), MMP-2 substrate unit (short peptide), anchoring unit (alkyl chain), and anchoring inhibition unit (polyethylene glycol (PEGn; where n represents the approximate molecular weight, n = 1000, 3000, and 5000). Probe cleavage was evaluated by chromatography after MMP-2 treatment. Cellular uptake of the probes was then measured. Radioactivity accumulation in tumor xenografts was evaluated after intravenous injection of the probes, and probe cleavage was evaluated in tumor homogenates. Results MDAP1000, MDAP3000, and MDAP5000 were cleaved by MMP-2 in a concentration-dependent manner. MDAP3000 pretreated with MMP-2 showed higher accumulation in tumor cells, and was completely blocked by additional treatment with an MMP inhibitor. MDAP3000 exhibited rapid blood clearance and a high tumor accumulation after intravenous injection in a rodent model. Furthermore, pharmacokinetic analysis revealed that MDAP3000 exhibited a considerably slow washout rate from tumors to blood. A certain fraction of cleaved MDAP3000 existed in tumor xenografts in vivo. Conclusions The results indicate the possible usefulness of our MDAP strategy for tumor imaging. PMID:25010662

  2. Superior sulcus tumors (Pancoast tumors).

    PubMed

    Marulli, Giuseppe; Battistella, Lucia; Mammana, Marco; Calabrese, Francesca; Rea, Federico

    2016-06-01

    Superior Sulcus Tumors, frequently termed as Pancoast tumors, are a wide range of tumors invading the apical chest wall. Due to its localization in the apex of the lung, with the potential invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, the superior sulcus tumors cause characteristic symptoms, like arm or shoulder pain or Horner's syndrome. The management of superior sulcus tumors has dramatically evolved over the past 50 years. Originally deemed universally fatal, in 1956, Shaw and Paulson introduced a new treatment paradigm with combined radiotherapy and surgery ensuring 5-year survival of approximately 30%. During the 1990s, following the need to improve systemic as well as local control, a trimodality approach including induction concurrent chemoradiotherapy followed by surgical resection was introduced, reaching 5-year survival rates up to 44% and becoming the standard of care. Many efforts have been persecuted, also, to obtain higher complete resection rates using appropriate surgical approaches and involving multidisciplinary team including spine surgeon or vascular surgeon. Other potential treatment options are under consideration like prophylactic cranial irradiation or the addition of other chemotherapy agents or biologic agents to the trimodality approach.

  3. Superior sulcus tumors (Pancoast tumors).

    PubMed

    Marulli, Giuseppe; Battistella, Lucia; Mammana, Marco; Calabrese, Francesca; Rea, Federico

    2016-06-01

    Superior Sulcus Tumors, frequently termed as Pancoast tumors, are a wide range of tumors invading the apical chest wall. Due to its localization in the apex of the lung, with the potential invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, the superior sulcus tumors cause characteristic symptoms, like arm or shoulder pain or Horner's syndrome. The management of superior sulcus tumors has dramatically evolved over the past 50 years. Originally deemed universally fatal, in 1956, Shaw and Paulson introduced a new treatment paradigm with combined radiotherapy and surgery ensuring 5-year survival of approximately 30%. During the 1990s, following the need to improve systemic as well as local control, a trimodality approach including induction concurrent chemoradiotherapy followed by surgical resection was introduced, reaching 5-year survival rates up to 44% and becoming the standard of care. Many efforts have been persecuted, also, to obtain higher complete resection rates using appropriate surgical approaches and involving multidisciplinary team including spine surgeon or vascular surgeon. Other potential treatment options are under consideration like prophylactic cranial irradiation or the addition of other chemotherapy agents or biologic agents to the trimodality approach. PMID:27429965

  4. Superior sulcus tumors (Pancoast tumors)

    PubMed Central

    Battistella, Lucia; Mammana, Marco; Calabrese, Francesca; Rea, Federico

    2016-01-01

    Superior Sulcus Tumors, frequently termed as Pancoast tumors, are a wide range of tumors invading the apical chest wall. Due to its localization in the apex of the lung, with the potential invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, the superior sulcus tumors cause characteristic symptoms, like arm or shoulder pain or Horner’s syndrome. The management of superior sulcus tumors has dramatically evolved over the past 50 years. Originally deemed universally fatal, in 1956, Shaw and Paulson introduced a new treatment paradigm with combined radiotherapy and surgery ensuring 5-year survival of approximately 30%. During the 1990s, following the need to improve systemic as well as local control, a trimodality approach including induction concurrent chemoradiotherapy followed by surgical resection was introduced, reaching 5-year survival rates up to 44% and becoming the standard of care. Many efforts have been persecuted, also, to obtain higher complete resection rates using appropriate surgical approaches and involving multidisciplinary team including spine surgeon or vascular surgeon. Other potential treatment options are under consideration like prophylactic cranial irradiation or the addition of other chemotherapy agents or biologic agents to the trimodality approach. PMID:27429965

  5. Radiation-induced nitric oxide mitigates tumor hypoxia and radioresistance in a murine SCCVII tumor model

    SciTech Connect

    Nagane, Masaki; Yasui, Hironobu; Yamamori, Tohru; Zhao, Songji; Kuge, Yuji; Tamaki, Nagara; Kameya, Hiromi; Nakamura, Hideo; Fujii, Hirotada; Inanami, Osamu

    2013-08-02

    Highlights: •IR-induced NO increased tissue perfusion and pO{sub 2}. •IR increased NO production in tumors without changes in the mRNA and protein levels of NOS isoforms. •NOS activity assay showed that IR upregulated eNOS activity in tumors. •IR-induced NO decreased tumor hypoxia and altered tumor radiosensitivity. -- Abstract: Tumor hypoxia, which occurs mainly as a result of inadequate tissue perfusion in solid tumors, is a well-known challenge for successful radiotherapy. Recent evidence suggests that ionizing radiation (IR) upregulates nitric oxide (NO) production and that IR-induced NO has the potential to increase intratumoral circulation. However, the kinetics of NO production and the responsible isoforms for NO synthase in tumors exposed to IR remain unclear. In this study, we aimed to elucidate the mechanism by which IR stimulates NO production in tumors and the effect of IR-induced NO on tumor radiosensitivity. Hoechst33342 perfusion assay and electron spin resonance oxymetry showed that IR increased tissue perfusion and pO{sub 2} in tumor tissue. Immunohistochemical analysis using two different hypoxic probes showed that IR decreased hypoxic regions in tumors; treatment with a nitric oxide synthase (NOS) inhibitor, L-NAME, abrogated the effects of IR. Moreover, IR increased endothelial NOS (eNOS) activity without affecting its mRNA or protein expression levels in SCCVII-transplanted tumors. Tumor growth delay assay showed that L-NAME decreased the anti-tumor effect of fractionated radiation (10 Gy × 2). These results suggested that IR increased eNOS activity and subsequent tissue perfusion in tumors. Increases in intratumoral circulation simultaneously decreased tumor hypoxia. As a result, IR-induced NO increased tumor radiosensitivity. Our study provides a new insight into the NO-dependent mechanism for efficient fractionated radiotherapy.

  6. High temperature probe

    DOEpatents

    Swan, Raymond A.

    1994-01-01

    A high temperature probe for sampling, for example, smokestack fumes, and is able to withstand temperatures of 3000.degree. F. The probe is constructed so as to prevent leakage via the seal by placing the seal inside the water jacket whereby the seal is not exposed to high temperature, which destroys the seal. The sample inlet of the probe is also provided with cooling fins about the area of the seal to provide additional cooling to prevent the seal from being destroyed. Also, a heated jacket is provided for maintaining the temperature of the gas being tested as it passes through the probe. The probe includes pressure sensing means for determining the flow velocity of an efficient being sampled. In addition, thermocouples are located in various places on the probe to monitor the temperature of the gas passing there through.

  7. An ultrafast reciprocating probe

    NASA Astrophysics Data System (ADS)

    Liu, Wenbin; Tan, Yi; Wang, Wenhao; Gao, Zhe

    2016-11-01

    For tokamak plasma diagnostics, an ultrafast reciprocating probe system driven by magnetic field coils, achieving a maximum velocity of 21 m/s, is introduced. The probes are attached with a driving hoop made of carbon steel and accelerated by three acceleration coils in series, then decelerated by two deceleration coils and buffer springs and return slowly. The coils with a current of about 1 kA generate a magnetic field of about 1 T. This probe system has been tested on the SUNIST (Sino-UNIted Spherical Tokamak) spherical tokamak. Radial profiles of the floating potential and other plasma parameters measured by this probe system are given.

  8. Atom probe tomography

    SciTech Connect

    Miller, M.K.; Forbes, R.G.

    2009-06-15

    This introductory tutorial describes the technique of atom probe tomography for materials characterization at the atomic level. The evolution of the technique from the initial atom probe field ion microscope to today's state-of-the-art three dimensional atom probe is outlined. An introduction is presented on the basic physics behind the technique, the operation of the instrument, and the reconstruction of the three-dimensional data. The common methods for analyzing the three-dimensional atom probe data, including atom maps, isoconcentration surfaces, proximity histograms, maximum separation methods, and concentration frequency distributions, are described.

  9. DNA Probe Pooling for Rapid Delineation of Chromosomal Breakpoints

    SciTech Connect

    Lu, Chun-Mei; Kwan, Johnson; Baumgartner, Adolf; Weier, Jingly F.; Wang, Mei; Escudero, Tomas; Munne', Santiago; Zitzelsberger, Horst F.; Weier, Heinz-Ulrich

    2009-01-30

    Structural chromosome aberrations are hallmarks of many human genetic diseases. The precise mapping of translocation breakpoints in tumors is important for identification of genes with altered levels of expression, prediction of tumor progression, therapy response, or length of disease-free survival as well as the preparation of probes for detection of tumor cells in peripheral blood. Similarly, in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) for carriers of balanced, reciprocal translocations benefit from accurate breakpoint maps in the preparation of patient-specific DNA probes followed by a selection of normal or balanced oocytes or embryos. We expedited the process of breakpoint mapping and preparation of case-specific probes by utilizing physically mapped bacterial artificial chromosome (BAC) clones. Historically, breakpoint mapping is based on the definition of the smallest interval between proximal and distal probes. Thus, many of the DNA probes prepared for multi-clone and multi-color mapping experiments do not generate additional information. Our pooling protocol described here with examples from thyroid cancer research and PGD accelerates the delineation of translocation breakpoints without sacrificing resolution. The turnaround time from clone selection to mapping results using tumor or IVF patient samples can be as short as three to four days.

  10. Radio frequency-compensated Langmuir probe with auxiliary double probes

    SciTech Connect

    Oh, Se-Jin; Oh, Seung-Ju; Chung, Chin-Wook

    2010-09-15

    A radio frequency (rf) compensation design using auxiliary double probes connected in parallel with a main measurement probe was developed for Langmuir probe diagnostics. This probe structure can reduce the sheath impedance of the main probe. In our probe design, the sheath capacitance of the probe can be increased and its sheath resistance can be decreased with increasing dc bias differential voltage between the auxiliary double probes. The I-V characteristic curve and electron energy distribution functions measured by our probe system had sufficient rf compensation performance in inductively coupled plasmas.

  11. Radio frequency-compensated Langmuir probe with auxiliary double probes.

    PubMed

    Oh, Se-Jin; Oh, Seung-Ju; Chung, Chin-Wook

    2010-09-01

    A radio frequency (rf) compensation design using auxiliary double probes connected in parallel with a main measurement probe was developed for Langmuir probe diagnostics. This probe structure can reduce the sheath impedance of the main probe. In our probe design, the sheath capacitance of the probe can be increased and its sheath resistance can be decreased with increasing dc bias differential voltage between the auxiliary double probes. The I-V characteristic curve and electron energy distribution functions measured by our probe system had sufficient rf compensation performance in inductively coupled plasmas.

  12. Brain tumor (image)

    MedlinePlus

    Brain tumors are classified depending on the exact site of the tumor, the type of tissue involved, benign ... tendencies of the tumor, and other factors. Primary brain tumors can arise from the brain cells, the meninges ( ...

  13. Understanding Brain Tumors

    MedlinePlus

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  14. Brain Tumor Diagnosis

    MedlinePlus

    ... Types of Brain Scans X-rays Laboratory Tests DNA Profiling Biopsy Procedure Malignant and Benign Brain Tumors Tumor ... Types of Brain Scans X-rays Laboratory Tests DNA Profiling Biopsy Procedure Malignant and Benign Brain Tumors Tumor ...

  15. Formative Assessment Probes

    ERIC Educational Resources Information Center

    Eberle, Francis; Keeley, Page

    2008-01-01

    Formative assessment probes can be effective tools to help teachers build a bridge between students' initial ideas and scientific ones. In this article, the authors describe how using two formative assessment probes can help teachers determine the extent to which students make similar connections between developing a concept of matter and a…

  16. PDV Probe Alignment Technique

    SciTech Connect

    Whitworth, T L; May, C M; Strand, O T

    2007-10-26

    This alignment technique was developed while performing heterodyne velocimetry measurements at LLNL. There are a few minor items needed, such as a white card with aperture in center, visible alignment laser, IR back reflection meter, and a microscope to view the bridge surface. The work was performed on KCP flyers that were 6 and 8 mils wide. The probes used were Oz Optics manufactured with focal distances of 42mm and 26mm. Both probes provide a spot size of approximately 80?m at 1550nm. The 42mm probes were specified to provide an internal back reflection of -35 to -40dB, and the probe back reflections were measured to be -37dB and -33dB. The 26mm probes were specified as -30dB and both measured -30.5dB. The probe is initially aligned normal to the flyer/bridge surface. This provides a very high return signal, up to -2dB, due to the bridge reflectivity. A white card with a hole in the center as an aperture can be used to check the reflected beam position relative to the probe and launch beam, and the alignment laser spot centered on the bridge, see Figure 1 and Figure 2. The IR back reflection meter is used to measure the dB return from the probe and surface, and a white card or similar object is inserted between the probe and surface to block surface reflection. It may take several iterations between the visible alignment laser and the IR back reflection meter to complete this alignment procedure. Once aligned normal to the surface, the probe should be tilted to position the visible alignment beam as shown in Figure 3, and the flyer should be translated in the X and Y axis to reposition the alignment beam onto the flyer as shown in Figure 4. This tilting of the probe minimizes the amount of light from the bridge reflection into the fiber within the probe while maintaining the alignment as near normal to the flyer surface as possible. When the back reflection is measured after the tilt adjustment, the level should be about -3dB to -6dB higher than the probes

  17. Inflatable traversing probe seal

    NASA Technical Reports Server (NTRS)

    Trimarchi, Paul A.

    1991-01-01

    An inflatable seal acts as a pressure-tight zipper to provide traversing capability for instrumentation rakes and probes. A specially designed probe segment with a teardrop cross-section in the vicinity of the inflatable seal minimizes leakage at the interface. The probe is able to travel through a lengthwise slot in a pressure vessel or wind tunnel section, while still maintaining pressure integrity. The design uses two commercially available inflatable seals, opposing each other, to cover the probe slot in a wind tunnel wall. Proof-of-concept tests were conducted at vessel pressures up to 30 psig, with seals inflated to 50 psig, showing no measurable leakage along the seal's length or around the probe teardrop cross-section. This seal concept can replace the existing technology of sliding face plate/O-ring systems in applications where lengthwise space is limited.

  18. Brain Tumor Symptoms

    MedlinePlus

    ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us Our Founders Board of Directors Staff ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning Donate to the ABTA Help advance the understanding ...

  19. Biomedical probe using a fiber-optic coupled scintillator.

    PubMed

    Swinth, K L; Ewins, J H

    1976-01-01

    A high-sensitivity biomedical radiation probe which employs a fiber-optic coupled NaI(Tl) scintillator as a detector is described. It was developed for in vivo counting of low-energy 239Pu photons from material located in the tracheobronchial lymph nodes.-This probe is 20 times as sensitive as a solid-state probe (avalanche diode) previously developed for this application. Tests with 99mTc show a sensitivity more than 90 times greater than biomedical probes using DcTe of GaAs; however, the improved sensitivity is largely due to an increased sensitive volume. Probes were evaluated in animals and phantoms for detection of 239Pu and for location of lung tumors labeled with 111In. PMID:1264039

  20. [Tumor surgery].

    PubMed

    Hausamen, J E

    2000-05-01

    Surgery is still the primary therapeutic approach in treatment of tumors in the head and neck area, dating back to the early nineteenth century. More than 150 years ago, hemimaxillectomies and mandibular resections as well as hemiglossectomies were already performed by leading surgeons. The block principle we are now following dates back to Crile, who also established the principle of cervical lymph node dissection. Ablative oncologic surgery has always been closely linked with plastic and reconstructive surgery, rendering radical surgical interventions possible without disfiguring patients. The development of facial reconstructive surgery proceeded in stages, in the first instance as secondary reconstruction using tube pedicled flaps. The change to the concept of primary reconstruction occurred via arterialized skin flaps and myocutaneous flaps to the widely accepted and performed free tissue transfer. Free bone grafting, inaugurated earlier and still representing the majority of bone grafting, has been supplemented for certain reconstructive purposes by free vascularized bone transfer from various donor sites. Although the five-year-survival rate of carcinoma of the oral cavity has remained unchanged in the past 30 years, distinctive improvements in tumor surgery can be recorded. This is primarily based on improved diagnostics such as modern imaging techniques and the refinement of surgical techniques. The DOSAK has worked out distinctive guidelines for effective ablative oncologic surgery. Surgical approaches offering wide exposure and carrying low morbidity play a decisive role in radical resections. For this reason, midfacial degloving offers an essential improvement for the resection of midface tumors, especially from an aesthetic point of view. Tumors situated deep behind the viscerocranium at the skull base can be clearly exposed either through a lateral approach following a temporary osteotomy of the mandibular ramus or a transmandibular, transmaxillar, or

  1. ALEX neutral beam probe

    SciTech Connect

    Pourrezaei, K.

    1982-01-01

    A neutral beam probe capable of measuring plasma space potential in a fully 3-dimensional magnetic field geometry has been developed. This neutral beam was successfully used to measure an arc target plasma contained within the ALEX baseball magnetic coil. A computer simulation of the experiment was performed to refine the experimental design and to develop a numerical model for scaling the ALEX neutral beam probe to other cases of fully 3-dimensional magnetic field. Based on this scaling a 30 to 50 keV neutral cesium beam probe capable of measuring space potential in the thermal barrier region of TMX Upgrade was designed.

  2. BEAM CONTROL PROBE

    DOEpatents

    Chesterman, A.W.

    1959-03-17

    A probe is described for intercepting a desired portion of a beam of charged particles and for indicating the spatial disposition of the beam. The disclosed probe assembly includes a pair of pivotally mounted vanes moveable into a single plane with adjacent edges joining and a calibrated mechanical arrangement for pivoting the vancs apart. When the probe is disposed in the path of a charged particle beam, the vanes may be adjusted according to the beam current received in each vane to ascertain the dimension of the beam.

  3. Focus: DNA probes

    SciTech Connect

    Not Available

    1986-11-01

    Progress in the development of DNA probes for the identification and quantitation of specific genetic sequences in biological samples is reviewed. Current research efforts in the development of DNA probes for the diagnosis of a wide variety of bacterial, viral, and other infectious diseases, such as herpes simplex and cytomegalovirus, and inherited genetic diseases such as cystic fibrosis and sickle cell anemia are discussed. Progress in development of DNA probe assays for cancer diagnosis, detection of Salmonella food poisoning, tissue typing (detection of histocompatibility antigens), mutagen screening, and animal diseases, among other applications is included.

  4. Foldable polymers as probes

    DOEpatents

    Li, Alexander D. Q.; Wang, Wei

    2007-07-03

    Disclosed herein are novel probes, which can be used to detect and identify target molecules of interest in a sample. The disclosed probes can be used to monitor conformational changes induced by molecular recognition events in addition to providing signaling the presence and/or identity of a target molecule. Methods, including solid phase synthesis techniques, for making probe molecules that exhibit changes in their optical properties upon target molecule binding are described in the disclosure. Also disclosed herein are novel chromophore moieties, which have tailored fluorescent emission spectra.

  5. Foldable polymers as probes

    DOEpatents

    Li, Alexander D. Q.; Wang, Wei

    2009-07-07

    Disclosed herein are novel probes, which can be used to detect and identify target molecules of interest in a sample. The disclosed probes can be used to monitor conformational changes induced by molecular recognition events in addition to providing signaling the presence and/or identity of a target molecule. Methods, including solid phase synthesis techniques, for making probe molecules that exhibit changes in their optical properties upon target molecule binding are described in the disclosure. Also disclosed herein are novel chromophore moieties, which have tailored fluorescent emission spectra.

  6. Transient enthalpy probe development

    NASA Astrophysics Data System (ADS)

    Bennett, Brian K.

    A reliable diagnostic probe has been developed to measure the local enthalpy in high-pressure, arc heated test streams that simulate atmospheric reentry conditions. The probe employs the double sonic-throat technique and is designed for the sweep (transient) mode to survive the severe heating environment. Tests in the high-pressure arc heater facilities show that, under certain conditions, the enthalpy probe measurements are in good agreement with enthalpy profiles inferred from heat flux measurements using the theory of Fay and Riddell (1958).

  7. Chemical sensing flow probe

    DOEpatents

    Laguna, George R.; Peter, Frank J.; Butler, Michael A.

    1999-01-01

    A new chemical probe determines the properties of an analyte using the light absorption of the products of a reagent/analyte reaction. The probe places a small reaction volume in contact with a large analyte volume. Analyte diffuses into the reaction volume. Reagent is selectively supplied to the reaction volume. The light absorption of the reaction in the reaction volume indicates properties of the original analyte. The probe is suitable for repeated use in remote or hostile environments. It does not require physical sampling of the analyte or result in significant regent contamination of the analyte reservoir.

  8. Chemical sensing flow probe

    DOEpatents

    Laguna, G.R.; Peter, F.J.; Butler, M.A.

    1999-02-16

    A new chemical probe determines the properties of an analyte using the light absorption of the products of a reagent/analyte reaction. The probe places a small reaction volume in contact with a large analyte volume. Analyte diffuses into the reaction volume. Reagent is selectively supplied to the reaction volume. The light absorption of the reaction in the reaction volume indicates properties of the original analyte. The probe is suitable for repeated use in remote or hostile environments. It does not require physical sampling of the analyte or result in significant regent contamination of the analyte reservoir. 7 figs.

  9. Technology for Entry Probes

    NASA Technical Reports Server (NTRS)

    Cutts, James A.; Arnold, James; Venkatapathy, Ethiraj; Kolawa, Elizabeth; Munk, Michelle; Wercinski, Paul; Laub, Bernard

    2005-01-01

    A viewgraph describing technologies for entry probes is presented. The topics include: 1) Entry Phase; 2) Descent Phase; 3) Long duration atmospheric observations; 4) Survivability at high temperatures; and 5) Summary.

  10. An Ultrasonographic Periodontal Probe

    NASA Astrophysics Data System (ADS)

    Bertoncini, C. A.; Hinders, M. K.

    2010-02-01

    Periodontal disease, commonly known as gum disease, affects millions of people. The current method of detecting periodontal pocket depth is painful, invasive, and inaccurate. As an alternative to manual probing, an ultrasonographic periodontal probe is being developed to use ultrasound echo waveforms to measure periodontal pocket depth, which is the main measure of periodontal disease. Wavelet transforms and pattern classification techniques are implemented in artificial intelligence routines that can automatically detect pocket depth. The main pattern classification technique used here, called a binary classification algorithm, compares test objects with only two possible pocket depth measurements at a time and relies on dimensionality reduction for the final determination. This method correctly identifies up to 90% of the ultrasonographic probe measurements within the manual probe's tolerance.

  11. Secondary optic nerve tumors.

    PubMed

    Christmas, N J; Mead, M D; Richardson, E P; Albert, D M

    1991-01-01

    Secondary tumors of the optic nerve are more common than primary optic nerve tumors. The involvement of the optic nerve may arise from direct invasion from intraocular malignancies, from hematopoietic malignancy, from meningeal carcinomatosis, or from distant primary tumors. Orbital tumors rarely invade the optic nerve, and brain tumors involve it only in their late stages.

  12. uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection

    PubMed Central

    Yang, Lily; Sajja, Hari Krishna; Cao, Zehong; Qian, Weiping; Bender, Laura; Marcus, Adam I.; Lipowska, Malgorzata; Wood, William C.; Wang, Y. Andrew

    2014-01-01

    Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with the early stage cancers. The ability to identify invasive tumor edges of the primary tumor, locally invaded small tumor lesions, and drug resistant residual tumors following neoadjuvant therapy during surgery should significantly reduce the incidence of local tumor recurrence and improve survival of cancer patients. In this study, we report that urokinase plasminogen activator (uPA) and its receptor (uPAR) are the ligand/cell surface target pair for the development of targeted optical imaging probes for enhancing imaging contrasts in the tumor border. Recombinant peptides of the amino terminal fragment (ATF) of the receptor binding domain of uPA were labeled with near infrared fluorescence (NIR) dye molecules either as peptide-imaging or peptide-conjugated nanoparticle imaging probes. Systemic delivery of the uPAR-targeted imaging probes in mice bearing orthotopic human breast or pancreatic tumor xenografts or mouse mammary tumors led to the accumulation of the probes in the tumor and stromal cells, resulting in strong signals for optical imaging of tumors and identification of tumor margins. Histological analysis showed that a high level of uPAR-targeted nanoparticles was present in the tumor edge or active tumor stroma immediately adjacent to the tumor cells. Furthermore, following targeted therapy using uPAR-targeted theranostic nanoparticles, residual tumors were detectable by optical imaging through the imaging contrasts produced by NIR-dye-labeled theranostic nanoparticles in drug resistant tumor cells. Therefore, results of our study support the potential of the development of uPAR-targeted imaging and theranostic agents for image-guided surgery. PMID:24396518

  13. Model for resonant plasma probe.

    SciTech Connect

    Warne, Larry Kevin; Johnson, William Arthur; Hebner, Gregory Albert; Jorgenson, Roy E.; Coats, Rebecca Sue

    2007-04-01

    This report constructs simple circuit models for a hairpin shaped resonant plasma probe. Effects of the plasma sheath region surrounding the wires making up the probe are determined. Electromagnetic simulations of the probe are compared to the circuit model results. The perturbing effects of the disc cavity in which the probe operates are also found.

  14. Tumors and Pregnancy

    MedlinePlus

    Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

  15. Pancreatic islet cell tumor

    MedlinePlus

    Complications of these tumors include: Diabetes Hormone crises (if the tumor releases certain types of hormones) Severe low blood sugar (from insulinomas) Severe ulcers in the stomach and small intestine (from gastrinomas) Spread of the tumor to the liver

  16. Childhood Brain Tumors

    MedlinePlus

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  17. Pathology of eyelid tumors

    PubMed Central

    Pe’er, Jacob

    2016-01-01

    The eyelids are composed of four layers: skin and subcutaneous tissue including its adnexa, striated muscle, tarsus with the meibomian glands, and the palpebral conjunctiva. Benign and malignant tumors can arise from each of the eyelid layers. Most eyelid tumors are of cutaneous origin, mostly epidermal, which can be divided into epithelial and melanocytic tumors. Benign epithelial lesions, cystic lesions, and benign melanocytic lesions are very common. The most common malignant eyelid tumors are basal cell carcinoma in Caucasians and sebaceous gland carcinoma in Asians. Adnexal and stromal tumors are less frequent. The present review describes the more important eyelid tumors according to the following groups: Benign and malignant epithelial tumors, benign and malignant melanocytic tumors, benign and malignant adnexal tumors, stromal eyelid tumors, lymphoproliferative and metastatic tumors, other rare eyelid tumors, and inflammatory and infections lesions that simulate neoplasms. PMID:27146927

  18. [Tumor formation in plants].

    PubMed

    Matveeva, T V; Lutova, L A; Nester, Iu

    2001-09-01

    The data on genetic tumors in plant species and interspecific hybrids, as well as the problems of Agrobacterium-induced tumors are reviewed. The role of the horizontal gene transfer in the induction of genetic tumors is discussed. PMID:11642121

  19. Pathology of eyelid tumors.

    PubMed

    Pe'er, Jacob

    2016-03-01

    The eyelids are composed of four layers: skin and subcutaneous tissue including its adnexa, striated muscle, tarsus with the meibomian glands, and the palpebral conjunctiva. Benign and malignant tumors can arise from each of the eyelid layers. Most eyelid tumors are of cutaneous origin, mostly epidermal, which can be divided into epithelial and melanocytic tumors. Benign epithelial lesions, cystic lesions, and benign melanocytic lesions are very common. The most common malignant eyelid tumors are basal cell carcinoma in Caucasians and sebaceous gland carcinoma in Asians. Adnexal and stromal tumors are less frequent. The present review describes the more important eyelid tumors according to the following groups: Benign and malignant epithelial tumors, benign and malignant melanocytic tumors, benign and malignant adnexal tumors, stromal eyelid tumors, lymphoproliferative and metastatic tumors, other rare eyelid tumors, and inflammatory and infections lesions that simulate neoplasms. PMID:27146927

  20. Overview of Heart Tumors

    MedlinePlus

    ... the heart. Most heart tumors are metastatic cancer. Did You Know... Noncancerous tumors can be as deadly ... slow the tumor's growth. Resources In This Article Did You Know 1 Did You Know... Table 2 ...

  1. Brain Tumors (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Brain Tumors KidsHealth > For Parents > Brain Tumors Print A ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  2. Surgical force detection probe

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Roberts, Paul; Scott, Charles; Prass, Richard

    1991-01-01

    The development progress of a precision electro-mechanical instrument which allows the detection and documentation of the forces and moment applied to human tissue during surgery (under actual operation room conditions), is reported. The pen-shaped prototype probe which measures 1/2 inch in diameter and 7 inches in length was fabricated using an aerodynamic balance. The aerodynamic balance, a standard wind tunnel force and moment sensing transducer, measures the forces and the moments transmitted through the surgeon's hand to the human tissue during surgery. The prototype probe which was fabricated as a development tool was tested successfully. The final version of the surgical force detection probe will be designed based on additional laboratory tests in order to establish the full scale loads. It is expected that the final product will require a simplified aerodynamic balance with two or three force components and one moment component with lighter full scale loads. A signal conditioner was fabricated to process and display the outputs from the prototype probe. This unit will be interfaced with a PC-based data system to provide automatic data acquisition, data processing, and graphics display. The expected overall accuracy of the probe is better than one percent full scale.

  3. Convective heat flow probe

    DOEpatents

    Dunn, James C.; Hardee, Harry C.; Striker, Richard P.

    1985-01-01

    A convective heat flow probe device is provided which measures heat flow and fluid flow magnitude in the formation surrounding a borehole. The probe comprises an elongate housing adapted to be lowered down into the borehole; a plurality of heaters extending along the probe for heating the formation surrounding the borehole; a plurality of temperature sensors arranged around the periphery of the probe for measuring the temperature of the surrounding formation after heating thereof by the heater elements. The temperature sensors and heater elements are mounted in a plurality of separate heater pads which are supported by the housing and which are adapted to be radially expanded into firm engagement with the walls of the borehole. The heat supplied by the heater elements and the temperatures measured by the temperature sensors are monitored and used in providing the desired measurements. The outer peripheral surfaces of the heater pads are configured as segments of a cylinder and form a full cylinder when taken together. A plurality of temperature sensors are located on each pad so as to extend along the length and across the width thereof, with a heating element being located in each pad beneath the temperature sensors. An expansion mechanism driven by a clamping motor provides expansion and retraction of the heater pads and expandable packer-type seals are provided along the probe above and below the heater pads.

  4. Convective heat flow probe

    DOEpatents

    Dunn, J.C.; Hardee, H.C.; Striker, R.P.

    1984-01-09

    A convective heat flow probe device is provided which measures heat flow and fluid flow magnitude in the formation surrounding a borehole. The probe comprises an elongate housing adapted to be lowered down into the borehole; a plurality of heaters extending along the probe for heating the formation surrounding the borehole; a plurality of temperature sensors arranged around the periphery of the probe for measuring the temperature of the surrounding formation after heating thereof by the heater elements. The temperature sensors and heater elements are mounted in a plurality of separate heater pads which are supported by the housing and which are adapted to be radially expanded into firm engagement with the walls of the borehole. The heat supplied by the heater elements and the temperatures measured by the temperature sensors are monitored and used in providing the desired measurements. The outer peripheral surfaces of the heater pads are configured as segments of a cylinder and form a full cylinder when taken together. A plurality of temperature sensors are located on each pad so as to extend along the length and across the width thereof, with a heating element being located in each pad beneath the temperature sensors. An expansion mechanism driven by a clamping motor provides expansion and retraction of the heater pads and expandable packet-type seals are provided along the probe above and below the heater pads.

  5. Ice-Borehole Probe

    NASA Technical Reports Server (NTRS)

    Behar, Alberto; Carsey, Frank; Lane, Arthur; Engelhardt, Herman

    2006-01-01

    An instrumentation system has been developed for studying interactions between a glacier or ice sheet and the underlying rock and/or soil. Prior borehole imaging systems have been used in well-drilling and mineral-exploration applications and for studying relatively thin valley glaciers, but have not been used for studying thick ice sheets like those of Antarctica. The system includes a cylindrical imaging probe that is lowered into a hole that has been bored through the ice to the ice/bedrock interface by use of an established hot-water-jet technique. The images acquired by the cameras yield information on the movement of the ice relative to the bedrock and on visible features of the lower structure of the ice sheet, including ice layers formed at different times, bubbles, and mineralogical inclusions. At the time of reporting the information for this article, the system was just deployed in two boreholes on the Amery ice shelf in East Antarctica and after successful 2000 2001 deployments in 4 boreholes at Ice Stream C, West Antarctica, and in 2002 at Black Rapids Glacier, Alaska. The probe is designed to operate at temperatures from 40 to +40 C and to withstand the cold, wet, high-pressure [130-atm (13.20-MPa)] environment at the bottom of a water-filled borehole in ice as deep as 1.6 km. A current version is being outfitted to service 2.4-km-deep boreholes at the Rutford Ice Stream in West Antarctica. The probe (see figure) contains a sidelooking charge-coupled-device (CCD) camera that generates both a real-time analog video signal and a sequence of still-image data, and contains a digital videotape recorder. The probe also contains a downward-looking CCD analog video camera, plus halogen lamps to illuminate the fields of view of both cameras. The analog video outputs of the cameras are converted to optical signals that are transmitted to a surface station via optical fibers in a cable. Electric power is supplied to the probe through wires in the cable at a

  6. Multispectral imaging probe

    DOEpatents

    Sandison, David R.; Platzbecker, Mark R.; Descour, Michael R.; Armour, David L.; Craig, Marcus J.; Richards-Kortum, Rebecca

    1999-01-01

    A multispectral imaging probe delivers a range of wavelengths of excitation light to a target and collects a range of expressed light wavelengths. The multispectral imaging probe is adapted for mobile use and use in confined spaces, and is sealed against the effects of hostile environments. The multispectral imaging probe comprises a housing that defines a sealed volume that is substantially sealed from the surrounding environment. A beam splitting device mounts within the sealed volume. Excitation light is directed to the beam splitting device, which directs the excitation light to a target. Expressed light from the target reaches the beam splitting device along a path coaxial with the path traveled by the excitation light from the beam splitting device to the target. The beam splitting device directs expressed light to a collection subsystem for delivery to a detector.

  7. Multispectral imaging probe

    DOEpatents

    Sandison, D.R.; Platzbecker, M.R.; Descour, M.R.; Armour, D.L.; Craig, M.J.; Richards-Kortum, R.

    1999-07-27

    A multispectral imaging probe delivers a range of wavelengths of excitation light to a target and collects a range of expressed light wavelengths. The multispectral imaging probe is adapted for mobile use and use in confined spaces, and is sealed against the effects of hostile environments. The multispectral imaging probe comprises a housing that defines a sealed volume that is substantially sealed from the surrounding environment. A beam splitting device mounts within the sealed volume. Excitation light is directed to the beam splitting device, which directs the excitation light to a target. Expressed light from the target reaches the beam splitting device along a path coaxial with the path traveled by the excitation light from the beam splitting device to the target. The beam splitting device directs expressed light to a collection subsystem for delivery to a detector. 8 figs.

  8. Ratiometric Fluorescent pH Probes Based on Glycopolymers.

    PubMed

    Li, Zhiyun; Zhang, Pengshan; Lu, Wei; Peng, Lun; Zhao, Yun; Chen, Gaojian

    2016-09-01

    Effectively detecting pH changes plays a critical role in exploring cellular functions and determining physiological and pathological processes. A novel ratiometric pH probe based on a glycopolymer, armored with properties of serum-stability, tumor-targeting, and pH monitoring, is designed. Random copolymers of 2-(methacrylamido) glucopyranose and fluorescein O-methacrylate are first synthesized by reversible addition fragmentation chain transfer polymerization. Acryloxyethyl thiocarbamoyl rhodamine B is then attached to the polymer chain to prepare ratiometric fluorescent pH probes via a thiol-ene reaction. The synthesized polymeric probes are characterized by NMR, gel permeation chromatography, UV-vis spectroscopy, and transmission electron microscopy, and the fluorescence responses are examined in phosphate buffer at different pHs. The cytotoxicity and confocal imaging experiments of the probes are detected using HeLa cells, demonstrating a low toxicity and superior biocompatibility for detecting pH changes in bioapplications. PMID:27439338

  9. Ratiometric Fluorescent pH Probes Based on Glycopolymers.

    PubMed

    Li, Zhiyun; Zhang, Pengshan; Lu, Wei; Peng, Lun; Zhao, Yun; Chen, Gaojian

    2016-09-01

    Effectively detecting pH changes plays a critical role in exploring cellular functions and determining physiological and pathological processes. A novel ratiometric pH probe based on a glycopolymer, armored with properties of serum-stability, tumor-targeting, and pH monitoring, is designed. Random copolymers of 2-(methacrylamido) glucopyranose and fluorescein O-methacrylate are first synthesized by reversible addition fragmentation chain transfer polymerization. Acryloxyethyl thiocarbamoyl rhodamine B is then attached to the polymer chain to prepare ratiometric fluorescent pH probes via a thiol-ene reaction. The synthesized polymeric probes are characterized by NMR, gel permeation chromatography, UV-vis spectroscopy, and transmission electron microscopy, and the fluorescence responses are examined in phosphate buffer at different pHs. The cytotoxicity and confocal imaging experiments of the probes are detected using HeLa cells, demonstrating a low toxicity and superior biocompatibility for detecting pH changes in bioapplications.

  10. A curved vitrectomy probe.

    PubMed

    Chalam, K V; Shah, Vinay A; Tripathi, Ramesh C

    2004-01-01

    A curved vitrectomy probe for better accessibility of the peripheral retina in phakic eyes is described. The specially designed curved vitrectomy probe has a 20-gauge pneumatic cutter. The radius of curvature at the shaft is 19.4 mm and it is 25 mm long. The ora serrata is accessed through a 3.0- or 4.0-mm sclerotomy in phakic eyes without touching the crystalline lens. Use of this instrument avoids inadvertent trauma to the clear lens in phakic eyes requiring vitreous base excision. This curved vitrectomy instrument complements wide-angle viewing systems and endoscopes for safe surgical treatment of peripheral retinal pathology in phakic eyes. PMID:15185799

  11. Galactose as Broad Ligand for Multiple Tumor Imaging and Therapy.

    PubMed

    Ma, Yuxiang; Chen, Haiyan; Su, Shanyuhan; Wang, Tong; Zhang, Congying; Fida, Guissi; Cui, Sisi; Zhao, Juan; Gu, Yueqing

    2015-01-01

    Galactose residues could be specifically recognized by the asialoglycoprotein receptor (ASGPR) which is highly exhibited on liver tissues. However, ASGPR has not been widely investigated on different tumor cell lines except for hepatoma carcinoma cells, which motivates us to investigate the possibility of galactose serving as a board tumor ligand. In this study, a galactose (Gal)-based probe conjugated with fluorescence dye MPA (Gal-MPA) was constructed for the evaluation of tumor affinities/targeted ability on different tumor cell lines. In the vitro cell study, it was indicated that the fluorescence probe Gal-MPA displayed higher cell affinity to tumor cells (HepG2, MCF-7 and A549) than that of the normal liver cells l02. In the vivo dynamic study of Gal-MPA in tumor-bearing mice (HepG2, MCF-7, A549, HCT116, U87, MDA-MB-231 and S180), it was shown that its high tumor targeted ability with the maximal tumor/normal tissue ratio reached up to 6.8. Meanwhile, the fast tumor-targeted ability within 2 hours and long retention on tumor site up to 120 hours were observed. Our results demonstrated that galactose should be a promising broad ligand for multiple tumor imaging and targeted therapy. Subsequently, Gal was covalently conjugated to doxorubicin (DOX) to form prodrug Gal-DOX for tumor targeted therapy. The therapeutic results of Gal-DOX than DOX being better suggested that galactosylated prodrugs might have the prospective potential in tumor targeted therapy.

  12. Galactose as Broad Ligand for Multiple Tumor Imaging and Therapy

    PubMed Central

    Ma, Yuxiang; Chen, Haiyan; Su, Shanyuhan; Wang, Tong; Zhang, Congying; Fida, Guissi; Cui, Sisi; Zhao, Juan; Gu, Yueqing

    2015-01-01

    Galactose residues could be specifically recognized by the asialoglycoprotein receptor (ASGPR) which is highly exhibited on liver tissues. However, ASGPR has not been widely investigated on different tumor cell lines except for hepatoma carcinoma cells, which motivates us to investigate the possibility of galactose serving as a board tumor ligand. In this study, a galactose (Gal)-based probe conjugated with fluorescence dye MPA (Gal-MPA) was constructed for the evaluation of tumor affinities/targeted ability on different tumor cell lines. In the vitro cell study, it was indicated that the fluorescence probe Gal-MPA displayed higher cell affinity to tumor cells (HepG2, MCF-7 and A549) than that of the normal liver cells l02. In the vivo dynamic study of Gal-MPA in tumor-bearing mice (HepG2, MCF-7, A549, HCT116, U87, MDA-MB-231 and S180), it was shown that its high tumor targeted ability with the maximal tumor/normal tissue ratio reached up to 6.8. Meanwhile, the fast tumor-targeted ability within 2 hours and long retention on tumor site up to 120 hours were observed. Our results demonstrated that galactose should be a promising broad ligand for multiple tumor imaging and targeted therapy. Subsequently, Gal was covalently conjugated to doxorubicin (DOX) to form prodrug Gal-DOX for tumor targeted therapy. The therapeutic results of Gal-DOX than DOX being better suggested that galactosylated prodrugs might have the prospective potential in tumor targeted therapy. PMID:26078797

  13. Neurochemistry and electroanalytical probes.

    PubMed

    Troyer, Kevin P; Heien, Michael L A V; Venton, B Jill; Wightman, R Mark

    2002-10-01

    Electroanalytical techniques have been applied to monitoring chemical events including neurotransmitter release during rodent behaviour and the release of zeptomoles of molecules from single cells. Transgenic mice models have been developed and studied to identify specific cell types in vitro. Characterization and surface modification of electroanalytical probes has enhanced the selectivity and sensitivity of measurements.

  14. Cervical Neoplasia Probe Control

    1997-01-24

    This software, which consists of a main executive and several subroutines, performs control of the optics, image acquisition, and Digital Signal Processing (DSP) of this image, of an optical based medical instrument that performs fluoresence detection of precancerous lesions (neoplasia) of the human cervix. The hardware portion of this medical instrument is known by the same name Cervical Neoplasia Probe (CNP)

  15. The Phoenix Pluto Probe

    NASA Technical Reports Server (NTRS)

    Gunning, George R.; Spapperi, Jeff; Wilkinson, Jeffrey P.; Eldred, Jim; Labij, Dennis; Strinni, Meredith

    1990-01-01

    A design proposal for an unmanned probe to Pluto is presented. The topics covered include: (1) scientific instrumentation; (2) mission management, planning, and costing; (3) power and propulsion system; (4) structural subsystem; (5) command, control, and communication; and (6) attitude and articulation control.

  16. Ultrasonic search wheel probe

    DOEpatents

    Mikesell, Charles R.

    1978-01-01

    A device is provided for reducing internal reflections from the tire of an ultrasonic search wheel probe or from within the material being examined. The device includes a liner with an anechoic chamber within which is an ultrasonic transducer. The liner is positioned within the wheel and includes an aperture through which the ultrasonic sound from the transducer is directed.

  17. Endocavity Ultrasound Probe Manipulators

    PubMed Central

    Stoianovici, Dan; Kim, Chunwoo; Schäfer, Felix; Huang, Chien-Ming; Zuo, Yihe; Petrisor, Doru; Han, Misop

    2014-01-01

    We developed two similar structure manipulators for medical endocavity ultrasound probes with 3 and 4 degrees of freedom (DoF). These robots allow scanning with ultrasound for 3-D imaging and enable robot-assisted image-guided procedures. Both robots use remote center of motion kinematics, characteristic of medical robots. The 4-DoF robot provides unrestricted manipulation of the endocavity probe. With the 3-DoF robot the insertion motion of the probe must be adjusted manually, but the device is simpler and may also be used to manipulate external-body probes. The robots enabled a novel surgical approach of using intraoperative image-based navigation during robot-assisted laparoscopic prostatectomy (RALP), performed with concurrent use of two robotic systems (Tandem, T-RALP). Thus far, a clinical trial for evaluation of safety and feasibility has been performed successfully on 46 patients. This paper describes the architecture and design of the robots, the two prototypes, control features related to safety, preclinical experiments, and the T-RALP procedure. PMID:24795525

  18. Experimenting with Temperature Probes.

    ERIC Educational Resources Information Center

    Roth, Wolff-Michael

    1989-01-01

    Presented are four activities which are designed to familiarize children with the multiple uses of computers and help them learn about heat and temperature using temperature probes. Included are the tempering effect of water, heat capacity, caloric content of foods, and weather. Hardware and software are discussed. (CW)

  19. Probing the Solar System

    ERIC Educational Resources Information Center

    Wilkinson, John

    2013-01-01

    Humans have always had the vision to one day live on other planets. This vision existed even before the first person was put into orbit. Since the early space missions of putting humans into orbit around Earth, many advances have been made in space technology. We have now sent many space probes deep into the Solar system to explore the planets and…

  20. Laboratory plasma probe studies

    NASA Technical Reports Server (NTRS)

    Heikkila, W. J.

    1975-01-01

    Diagnostic experiments performed in a collisionless plasma using CO2 as the working gas are described. In particular, simultaneous measurements that have been performed by means of Langmuir- and RF-probes are presented. A resonance occurring above the parallel resonance in the frequency characteristic of a two electrode system is interpreted as being due to the resonant excitation of electroacoustic waves.

  1. Optoacoustic probe for prostate cancer diagnostics

    NASA Astrophysics Data System (ADS)

    Andreev, Valeriy G.; Karabutov, Alexander A.; Oraevsky, Alexander

    2002-11-01

    The optoacoustic probe for prostate cancer detection was developed and tested. The 10-ns pulses of the YAG:Nd laser were delivered by an optical fiber with a turning mirror at its tip. A fiber tip was placed above an ultrasonic array which was employed for the detection of acoustic transients excited inside prostate tissue. The increased infrared light absorption inside prostate tumors resulted in acoustic pulses with enhanced peak pressure providing 200%-300% optoacoustic contrast. The transducer array and the optical fiber were wrapped inside a 20-mm diameter thin cylindrical shell filled with ultrasonic gel transparent for infrared radiation. Each acoustic transducer was made of 0.05-mm thick PVDF film with dimensions of 1 mm x12 mm. The frequency bandwidth of transducer array provided 0.3-mm axial in-depth resolution. The lateral resolution is defined by the array length and was estimated as 0.8-mm for 32-element array with 1-mm gap between transducers. Transducer sensitivity of 0.05 mV/Pa allowed the detection of 2-mm tumor located at 50 mm depth. The optoacoustic probe performance was evaluated via the acquisition of two-dimensional optoacoustic images of small absorbing spheres in prostate-tissue phantoms. [Work supported by NIH and FIRCA grants.

  2. Pediatric Odontogenic Tumors.

    PubMed

    Abrahams, Joshua M; McClure, Shawn A

    2016-02-01

    Pediatric odontogenic tumors are rare, and are often associated with impacted teeth. Although they can develop anywhere in the jaws, odontogenic tumors mainly occur in the posterior mandible. This article discusses the diagnosis and treatment of the most common pediatric odontogenic tumors, such as ameloblastoma, keratocystic odontogenic tumor, odontoma, and cementoblastoma.

  3. Tumor heterogeneity and circulating tumor cells.

    PubMed

    Zhang, Chufeng; Guan, Yan; Sun, Yulan; Ai, Dan; Guo, Qisen

    2016-05-01

    In patients with cancer, individualized treatment strategies are generally guided by an analysis of molecular biomarkers. However, genetic instability allows tumor cells to lose monoclonality and acquire genetic heterogeneity, an important characteristic of tumors, during disease progression. Researchers have found that there is tumor heterogeneity between the primary tumor and metastatic lesions, between different metastatic lesions, and even within a single tumor (either primary or metastatic). Tumor heterogeneity is associated with heterogeneous protein functions, which lowers diagnostic precision and consequently becomes an obstacle to determining the appropriate therapeutic strategies for individual cancer patients. With the development of novel testing technologies, an increasing number of studies have attempted to explore tumor heterogeneity by examining circulating tumor cells (CTCs), with the expectation that CTCs may comprehensively represent the full spectrum of mutations and/or protein expression alterations present in the cancer. In addition, this strategy represents a minimally invasive approach compared to traditional tissue biopsies that can be used to dynamically monitor tumor evolution. The present article reviews the potential efficacy of using CTCs to identify both spatial and temporal tumor heterogeneity. This review also highlights current issues in this field and provides an outlook toward future applications of CTCs.

  4. Pathogenesis of pituitary tumors.

    PubMed

    Yu, Run; Melmed, Shlomo

    2010-01-01

    Pituitary tumors are common and mostly benign neoplasia which cause excess or deficiency of pituitary hormones and compressive damage to adjacent organs. Oncogene activation [e.g. PTTG (pituitary tumor-transforming gene) and HMGA2], tumor suppressor gene inactivation (e.g. MEN1 and PRKAR1A), epigenetic changes (e.g. methylation) and humoral factors (e.g. ectopic production of stimulating hormones) are all possible pituitary tumor initiators; the micro-environment of pituitary tumors including steroid milieu, angiogenesis and abnormal cell adhesion further promote tumor growth. Senescence, a cellular defence mechanism against malignant transformation, may explain the benign nature of at least some pituitary tumors. We suggest that future research on pituitary tumor pathogenesis should incorporate systems approaches, and address regulatory mechanisms for pituitary cell proliferation, development of new animal models of pituitary tumor and isolation of functional human pituitary tumor cell lines. PMID:20541667

  5. Characterizing intraocular tumors with photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Xu, Guan; Xue, Yafang; Gursel, Zeynep; Slimani, Naziha; Wang, Xueding; Demirci, Hakan

    2016-03-01

    Intraocular tumors are life-threatening conditions. Long-term mortality from uveal melanoma, which accounts for 80% of primary intraocular tumors, could be as high as 25% depending on the size, ciliary body involvement and extraocular extension. The treatments of intraocular tumors include eye-sparing approaches such as radiotherapy and thermotherapy, and the more aggressive enucleation. The accurate diagnosis of intraocular tumors is thereby critical in the management and follow-up of the patients. The diagnosis of intraocular tumors is usually based on clinical examination with acoustic backscattering based ultrasonography. By analyzing the high frequency fluctuations within the ultrasound (US) signals, microarchitecture information inside the tumor can be characterized. However, US cannot interrogate the histochemical components formulating the microarchitecture. One representative example is the inability of US imaging (and other contemporary imaging modalities as well) in differentiating nevoid and melanoma cells as the two types of cells possesses similar acoustic backscattering properties. Combining optical and US imaging, photoacoustic (PA) measurements encode both the microarchitecture and histochemical component information in biological tissue. This study attempts to characterize ocular tumors by analyzing the high frequency signal components in the multispectral PA images. Ex vivo human eye globes with melanoma and retinoblastoma tumors were scanned using less than 6 mJ per square centimeters laser energy with tunable range of 600-1700 nm. A PA-US parallel imaging system with US probes CL15-7 and L22-14 were used to acquire the high frequency PA signals in real time. Preliminary results show that the proposed method can identify uveal melanoma against retinoblastoma tumors.

  6. Progress on the diagnosis and evaluation of brain tumors

    PubMed Central

    Gao, Huile

    2013-01-01

    Abstract Brain tumors are one of the most challenging disorders encountered, and early and accurate diagnosis is essential for the management and treatment of these tumors. In this article, diagnostic modalities including single-photon emission computed tomography, positron emission tomography, magnetic resonance imaging, and optical imaging are reviewed. We mainly focus on the newly emerging, specific imaging probes, and their potential use in animal models and clinical settings. PMID:24334439

  7. Calibration Fixture For Anemometer Probes

    NASA Technical Reports Server (NTRS)

    Lewis, Charles R.; Nagel, Robert T.

    1993-01-01

    Fixture facilitates calibration of three-dimensional sideflow thermal anemometer probes. With fixture, probe oriented at number of angles throughout its design range. Readings calibrated as function of orientation in airflow. Calibration repeatable and verifiable.

  8. Imaging tumor hypoxia by magnetic resonance methods.

    PubMed

    Pacheco-Torres, Jesús; López-Larrubia, Pilar; Ballesteros, Paloma; Cerdán, Sebastián

    2011-01-01

    Tumor hypoxia results from the negative balance between the oxygen demands of the tissue and the capacity of the neovasculature to deliver sufficient oxygen. The resulting oxygen deficit has important consequences with regard to the aggressiveness and malignancy of tumors, as well as their resistance to therapy, endowing the imaging of hypoxia with vital repercussions in tumor prognosis and therapy design. The molecular and cellular events underlying hypoxia are mediated mainly through hypoxia-inducible factor, a transcription factor with pleiotropic effects over a variety of cellular processes, including oncologic transformation, invasion and metastasis. However, few methodologies have been able to monitor noninvasively the oxygen tensions in vivo. MRI and MRS are often used for this purpose. Most MRI approaches are based on the effects of the local oxygen tension on: (i) the relaxation times of (19)F or (1)H indicators, such as perfluorocarbons or their (1)H analogs; (ii) the hemodynamics and magnetic susceptibility effects of oxy- and deoxyhemoglobin; and (iii) the effects of paramagnetic oxygen on the relaxation times of tissue water. (19)F MRS approaches monitor tumor hypoxia through the selective accumulation of reduced nitroimidazole derivatives in hypoxic zones, whereas electron spin resonance methods determine the oxygen level through its influence on the linewidths of appropriate paramagnetic probes in vivo. Finally, Overhauser-enhanced MRI combines the sensitivity of EPR methodology with the resolution of MRI, providing a window into the future use of hyperpolarized oxygen probes.

  9. Modular Rake of Pitot Probes

    NASA Technical Reports Server (NTRS)

    Dunlap, Timothy A.; Henry, Michael W.; Homyk, Raymond P.

    2004-01-01

    The figure presents selected views of a modular rake of 17 pitot probes for measuring both transient and steady-state pressures in a supersonic wind tunnel. In addition to pitot tubes visible in the figure, the probe modules contain (1) high-frequency dynamic-pressure transducers connected through wires to remote monitoring circuitry and (2) flow passages that lead to tubes that, in turn, lead to remote steady-state pressure transducers. Prior pitot-probe rakes were fabricated as unitary structures, into which the individual pitot probes were brazed. Repair or replacement of individual probes was difficult, costly, and time-consuming because (1) it was necessary to remove entire rakes in order to unbraze individual malfunctioning probes and (2) the heat of unbrazing a failed probe and of brazing a new probe in place could damage adjacent probes. In contrast, the modules in the present probe are designed to be relatively quickly and easily replaceable with no heating and, in many cases, without need for removal of the entire rake from the wind tunnel. To remove a malfunctioning probe, one first removes a screw-mounted V-cross-section cover that holds the probe and adjacent probes in place. Then one removes a screw-mounted cover plate to gain access to the steady-state pressure tubes and dynamicpressure wires. Next, one disconnects the tube and wires of the affected probe. Finally, one installs a new probe in the reverse of the aforementioned sequence. The wire connections can be made by soldering, but to facilitate removal and installation, they can be made via miniature plugs and sockets. The connections between the probe flow passages and the tubes leading to the remote pressure sensors can be made by use of any of a variety of readily available flexible tubes that can be easily pulled off and slid back on for removal and installation, respectively.

  10. Heavy ion beam probing

    SciTech Connect

    Hickok, R L

    1980-07-01

    This report consists of the notes distributed to the participants at the IEEE Mini-Course on Modern Plasma Diagnostics that was held in Madison, Wisconsin in May 1980. It presents an overview of Heavy Ion Beam Probing that briefly describes the principles and discuss the types of measurements that can be made. The problems associated with implementing beam probes are noted, possible variations are described, estimated costs of present day systems, and the scaling requirements for large plasma devices are presented. The final chapter illustrates typical results that have been obtained on a variety of plasma devices. No detailed calculations are included in the report, but a list of references that will provide more detailed information is included.

  11. Probing properties of cold radiofrequency plasma with polymer probe

    NASA Astrophysics Data System (ADS)

    Bormashenko, E.; Chaniel, G.; Multanen, V.

    2015-01-01

    The probe intended for the characterization of cold plasma is introduced. The probe allows the estimation of Debye length of cold plasma. The probe is based on the pronounced modification of surface properties (wettability) of polymer films by cold plasmas. The probe was tested with the cold radiofrequency inductive air plasma discharge. The Debye length and the concentration of charge carriers were estimated for various gas pressures. The reported results coincide reasonably with the corresponding values established by other methods. The probe makes possible measurement of characteristics of cold plasmas in closed chambers.

  12. Pancreas tumor interstitial pressure catheter measurement

    NASA Astrophysics Data System (ADS)

    Nieskoski, Michael D.; Gunn, Jason; Marra, Kayla; Trembly, B. Stuart; Pogue, Brian W.

    2016-03-01

    This paper highlights the methodology in measuring interstitial pressure in pancreatic adenocarcinoma tumors. A Millar Mikrotip pressure catheter (SPR-671) was used in this study and a system was built to amplify and filter the output signal for data collection. The Millar pressure catheter was calibrated prior to each experiment in a water column at 37°C, range of 0 to 60 inH2O (112 mmHg), resulting in a calibration factor of 33 mV / 1 inH2O. The interstitial pressures measured in two orthotopically grown pancreatic adenocarcinoma tumor were 57 mmHg and 48 mmHg, respectively. Verteporfin uptake into the pancreatic adenocarcinoma tumor was measured using a probe-based experimental dosimeter.

  13. Gravity Probe B Inspection

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The space vehicle Gravity Probe B (GP-B) is the relativity experiment developed at Stanford University to test two extraordinary predictions of Albert Einstein's general theory of relativity. The experiment will measure, very precisely, the expected tiny changes in the direction of the spin axes of four gyroscopes contained in an Earth-orbiting satellite at a 400-mile altitude. So free are the gyroscopes from disturbance that they will provide an almost perfect space-time reference system. They will measure how space and time are very slightly warped by the presence of the Earth, and, more profoundly, how the Earth's rotation very slightly drags space-time around with it. These effects, though small for the Earth, have far-reaching implications for the nature of matter and the structure of the Universe. GP-B is among the most thoroughly researched programs ever undertaken by NASA. This is the story of a scientific quest in which physicists and engineers have collaborated closely over many years. Inspired by their quest, they have invented a whole range of technologies that are already enlivening other branches of science and engineering. In this photograph, engineer Gary Reynolds is inspecting the inside of the probe neck during probe thermal repairs. GP-B is scheduled for launch in April 2004 and managed for NASA by the Marshall Space Flight Center. Development of the GP-B is the responsibility of Stanford University along with major subcontractor Lockheed Martin Corporation. (Image credit to Russ Leese, Gravity Probe B, Stanford University)

  14. Space Probe Launch

    NASA Technical Reports Server (NTRS)

    1970-01-01

    Managed by Marshall Space Flight Center, the Space Tug was a reusable multipurpose space vehicle designed to transport payloads to different orbital inclinations. Utilizing mission-specific combinations of its three primary modules (crew, propulsion, and cargo) and a variety of supplementary kits, the Space Tug was capable of numerous space applications. This 1970 artist's concept depicts the Tug's propulsion module launching a space probe into lunar orbit.

  15. [Tumor-induced immunosuppression].

    PubMed

    Paul, S; Calmels, B; Régulier, E

    2002-01-01

    Tumor immunology is based on two essential concepts: immune surveillance, which implicate the host immune reactions against tumor cells, and tumor immune escape, which refers to the tumor-cell evasion process against the host immune system. The notion that a deficit in immune cell functions permits tumor growth has received experimental support with the discovery of several different biochemical defects in T lymphocytes that infiltrate cancers. Furthermore, expression of self-antigens on the tumor surface impose potential barriers to the development of effective immune response. Tumors are able to overcome immune surveillance by changing the polarity of effectors cells, thus down-regulating the proliferation of tumor-specific cytotoxic T cells, or altering the effector compositions of immune cells within the tumor milieu, or both. Understanding the interaction between cancer cells and host immune cells is of importance for clinical applications or immunotherapy in cancer treatment. PMID:11937439

  16. Salivary gland tumors.

    PubMed

    Fitzpatrick, P J; Black, K M

    1985-10-01

    A retrospective review of 643 patients with salivary gland tumors seen between 1958-72 is reported. There were 328 malignant and 375 benign tumors. All patients with malignant tumors were assessed in a multidisciplinary head and neck clinic. The median age for developing malignant tumors was 58 and there was a male to female ratio of 1.2:1. For benign tumors the median age was 46 years and the male to female ratio 0.8:1. Overall the primary tumor was controlled by the first planned treatment in 145 (44%) malignant tumors and in 253 (80%) benign tumors. The five and 10 year actuarial survival for malignant tumors was 59.4% and 45.6% respectively.

  17. Icing Sensor Probe

    NASA Technical Reports Server (NTRS)

    Emery, Edward; Kok, Gregory L.

    2002-01-01

    Aircraft icing is a serious safety problem for the general aviation and some commuter transport airplanes. There has been tremendous growth in the commuter aviation industry in the last few years, Since these type of aircraft generally operate at lower altitudes they consequently spend a far greater proportion of their time operating in icing conditions. For the past thirty years airborne and ground based facilities have relied primarily on two types of cloud physics instrumentation to measure the characteristics of icing clouds: hot wire liquid water content probes and laser based particle sizing probes for the measurement of water droplet size. The instrumentation is severely limited by the technology that was developed during the 1970's and is quite large in size. The goal of this research is to develop one instrument with a wide bandwidth, better response time, higher resolution, user selectability, and small and lightweight. NASA Glenn Research Center, Droplet Measurement Technology, and Meteorology Society of Canada have developed a collaborative effort to develop such an instrument. This paper describes the development and test results of the prototype Icing Sensor Probe.

  18. Einstein Inflationary Probe (EIP)

    NASA Technical Reports Server (NTRS)

    Hinshaw, Gary

    2004-01-01

    I will discuss plans to develop a concept for the Einstein Inflation Probe: a mission to detect gravity waves from inflation via the unique signature they impart to the cosmic microwave background (CMB) polarization. A sensitive CMB polarization satellite may be the only way to probe physics at the grand-unified theory (GUT) scale, exceeding by 12 orders of magnitude the energies studied at the Large Hadron Collider. A detection of gravity waves would represent a remarkable confirmation of the inflationary paradigm and set the energy scale at which inflation occurred when the universe was a fraction of a second old. Even a strong upper limit to the gravity wave amplitude would be significant, ruling out many common models of inflation, and pointing to inflation occurring at much lower energy, if at all. Measuring gravity waves via the CMB polarization will be challenging. We will undertake a comprehensive study to identify the critical scientific requirements for the mission and their derived instrumental performance requirements. At the core of the study will be an assessment of what is scientifically and experimentally optimal within the scope and purpose of the Einstein Inflation Probe.

  19. Nanoscale thermal probing

    PubMed Central

    Yue, Yanan; Wang, Xinwei

    2012-01-01

    Nanoscale novel devices have raised the demand for nanoscale thermal characterization that is critical for evaluating the device performance and durability. Achieving nanoscale spatial resolution and high accuracy in temperature measurement is very challenging due to the limitation of measurement pathways. In this review, we discuss four methodologies currently developed in nanoscale surface imaging and temperature measurement. To overcome the restriction of the conventional methods, the scanning thermal microscopy technique is widely used. From the perspective of measuring target, the optical feature size method can be applied by using either Raman or fluorescence thermometry. The near-field optical method that measures nanoscale temperature by focusing the optical field to a nano-sized region provides a non-contact and non-destructive way for nanoscale thermal probing. Although the resistance thermometry based on nano-sized thermal sensors is possible for nanoscale thermal probing, significant effort is still needed to reduce the size of the current sensors by using advanced fabrication techniques. At the same time, the development of nanoscale imaging techniques, such as fluorescence imaging, provides a great potential solution to resolve the nanoscale thermal probing problem. PMID:22419968

  20. Development of photostabilized asymmetrical cyanine dyes for in vivo photoacoustic imaging of tumors.

    PubMed

    Onoe, Satoru; Temma, Takashi; Kanazaki, Kengo; Ono, Masahiro; Saji, Hideo

    2015-09-01

    Photoacoustic imaging (PAI) contributes to tumor diagnosis through the use of PAI probes that effectively accumulate in tumors. Previously, we developed a symmetrical cyanine dye, IC7-1-Bu, which showed high potential as a PAI probe because of its high tumor targeting ability and sufficient in vivo PA signal. However, IC7-1-Bu lacks photostability for multiple laser irradiations, so we developed stabilized PAI probes using IC7-1-Bu as a lead compound. We focused on the effect of singlet oxygen (1O2) generated by excited PAI probes on probe degeneration. We introduced a triplet-state quencher (TSQ) moiety into IC7-1-Bu to quench 1O2 generation and designed three IC-n-T derivatives with different linker lengths (n indicates linker length). The IC-n-T derivatives emitted in vitro PA signals that were comparable to IC7-1-Bu and significantly reduced 1O2 generation while showing improved photostability against multiple irradiations. Of the three derivatives evaluated, IC-5-T accumulated in tumors effectively to allow clear PAI of tumors in vivo. Furthermore, the photostability of IC-5-T was 1.5-fold higher than that of IC7-1-Bu in in vivo sequential PAI. These results suggest that IC-5-T is a potential PAI probe for in vivo sequential tumor imaging.

  1. Nine New Fluorescent Probes

    NASA Astrophysics Data System (ADS)

    Lin, Tsung-I.; Jovanovic, Misa V.; Dowben, Robert M.

    1989-06-01

    Absorption and fluorescence spectroscopic studies are reported here for nine new fluorescent probes recently synthesized in our laboratories: four pyrene derivatives with substituents of (i) 1,3-diacetoxy-6,8-dichlorosulfonyl, (ii) 1,3-dihydroxy-6,8-disodiumsulfonate, (iii) 1,3-disodiumsulfonate, and (iv) l-ethoxy-3,6,8-trisodiumsulfonate groups, and five [7-julolidino] coumarin derivatives with substituents of (v) 3-carboxylate-4-methyl, (vi) 3- methylcarboxylate, (vii) 3-acetate-4-methyl, (viii) 3-propionate-4-methyl, and (ix) 3-sulfonate-4-methyl groups. Pyrene compounds i and ii and coumarin compounds v and vi exhibit interesting absorbance and fluorescence properties: their absorption maxima are red shifted compared to the parent compound to the blue-green region, and the band width broadens considerably. All four blue-absorbing dyes fluoresce intensely in the green region, and the two pyrene compounds emit at such long wavelengths without formation of excimers. The fluorescence properties of these compounds are quite environment-sensitive: considerable spectral shifts and fluorescence intensity changes have been observed in the pH range from 3 to 10 and in a wide variety of polar and hydrophobic solvents with vastly different dielectric constants. The high extinction and fluorescence quantum yield of these probes make them ideal fluorescent labeling reagents for proteins, antibodies, nucleic acids, and cellular organelles. The pH and hydrophobicity-dependent fluorescence changes can be utilized as optical pH and/or hydrophobicity indicators for mapping environmental difference in various cellular components in a single cell. Since all nine probes absorb in the UV, but emit at different wavelengths in the visible, these two groups of compounds offer an advantage of utilizing a single monochromatic light source (e.g., a nitrogen laser) to achieve multi-wavelength detection for flow cytometry application. As a first step to explore potential application in

  2. Comparative evaluation of probing depth and clinical attachment level using a manual probe and Florida probe

    PubMed Central

    Kour, Amandeep; Kumar, Ashish; Puri, Komal; Khatri, Manish; Bansal, Mansi; Gupta, Geeti

    2016-01-01

    Background: To compare and evaluate the intra- and inter-examiner efficacy and reproducibility of the first-generation manual (Williams) probe and the third-generation Florida probe in terms of measuring pocket probing depth (PD) and clinical attachment level (CAL). Materials and Methods: Forty subjects/4000 sites were included in this comparative, cross-sectional study. Group- and site-wise categorizations were done. Based on gingival index, PD, and CAL, patients were divided into four groups, i.e., periodontally healthy, gingivitis, mild to moderate periodontitis, and severe periodontitis. Further, based on these parameters, a total of 4000 sites, with 1000 sites in each category randomly selected from these 40 patients, were taken. Full mouth PD and CAL measurements were recorded with two probes, by Examiner 1 and on Ramfjord teeth by Examiner 2. Results: Full mouth and Ramfjord teeth group- and site-wise PD obtained with the manual probe by both the examiners were statistically significantly deeper than that obtained with the Florida probe. The full mouth and Ramfjord teeth mean CAL measurement by Florida probe was higher as compared to manual probe in mild to moderate periodontitis group and sites, whereas in severe periodontitis group and sites, manual probe recorded higher CAL as compared to Florida probe. Conclusion: Mean PD and CAL measurements were deeper with the manual probe as compared to the Florida probe in all the groups and sites, except for the mild-moderate periodontitis group and sites where the CAL measurements with the manual probe were less than the Florida probe. Manual probe was more reproducible and showed less interexaminer variability as compared to the Florida probe. PMID:27563204

  3. Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors

    PubMed Central

    Kanazaki, Kengo; Sano, Kohei; Makino, Akira; Homma, Tsutomu; Ono, Masahiro; Saji, Hideo

    2016-01-01

    Photoacoustic imaging, which enables high-resolution imaging in deep tissues, has lately attracted considerable attention. For tumor imaging, photoacoustic probes have been proposed to enhance the photoacoustic effect to improve detection sensitivity. Here, we evaluated the feasibility of using a biocompatible hydrophilic polymer, polyoxazoline, conjugated with indocyanine green (ICG) as a tumor-targeted photoacoustic probe via enhanced permeability and retention effect. ICG molecules were multivalently conjugated to partially hydrolyzed polyoxazoline, thereby serving as highly sensitive photoacoustic probes. Interestingly, loading multiple ICG molecules to polyoxazoline significantly enhanced photoacoustic signal intensity under the same ICG concentration. In vivo biodistribution studies using tumor bearing mice demonstrated that 5% hydrolyzed polyoxazoline (50 kDa) conjugated with ICG (ICG/polyoxazoline = 7.8), P14-ICG7.8, showed relatively high tumor accumulation (9.4%ID/g), resulting in delivery of the highest dose of ICG among the probes tested. P14-ICG7.8 enabled clear visualization of the tumor regions by photoacoustic imaging 24 h after administration; the photoacoustic signal increased in proportion with the injected dose. In addition, the signal intensity in blood vessels in the photoacoustic images did not show much change, which was attributed to the high tumor-to-blood ratios of P14-ICG7.8. These results suggest that polyoxazoline-ICG would serve as a robust probe for sensitive photoacoustic tumor imaging. PMID:27667374

  4. Photo-click construction of a targetable and activatable two-photon probe imaging protease in apoptosis.

    PubMed

    Zhou, Mi; Hu, Jing; Zheng, Mengmeng; Song, Qinhua; Li, Jinbo; Zhang, Yan

    2016-02-01

    A photo-click reaction was used as an efficient method to construct two-photon fluorescent probes bearing two functional peptides for targeting and for protease cleavage respectively. The activatable two-photon probe constructed by this method was applied to two-photon imaging of caspase-3 both in cellular apoptosis and in tumor tissue.

  5. Utilizing Gold Nanoparticle Probes to Visually Detect DNA Methylation

    NASA Astrophysics Data System (ADS)

    Chen, Kui; Zhang, Mingyi; Chang, Ya-Nan; Xia, Lin; Gu, Weihong; Qin, Yanxia; Li, Juan; Cui, Suxia; Xing, Gengmei

    2016-06-01

    The surface plasmon resonance (SPR) effect endows gold nanoparticles (GNPs) with the ability to visualize biomolecules. In the present study, we designed and constructed a GNP probe to allow the semi-quantitative analysis of methylated tumor suppressor genes in cultured cells. To construct the probe, the GNP surfaces were coated with single-stranded DNA (ssDNA) by forming Au-S bonds. The ssDNA contains a thiolated 5'-end, a regulatory domain of 12 adenine nucleotides, and a functional domain with absolute pairing with methylated p16 sequence (Met- p16). The probe, paired with Met- p16, clearly changed the color of aggregating GNPs probe in 5 mol/L NaCl solution. Utilizing the probe, p16 gene methylation in HCT116 cells was semi-quantified. Further, the methylation of E-cadherin, p15, and p16 gene in Caco2, HepG2, and HCT116 cell lines were detected by the corresponding probes, constructed with three domains. This simple and cost-effective method was useful for the diagnosis of DNA methylation-related diseases.

  6. Stages of Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  7. Brain Tumor Statistics

    MedlinePlus

    ... facts and statistics here include brain and central nervous system tumors (including spinal cord, pituitary and pineal gland ... U.S. living with a primary brain and central nervous system tumor. This year, nearly 17,000 people will ...

  8. Pituitary Tumors: Condition Information

    MedlinePlus

    ... stress. Growth hormone helps control body growth and metabolism. Thyroid-stimulating hormone is involved in growth, body temperature, and heart rate. Nonfunctioning pituitary tumors (also called nonsecretory tumors) do ...

  9. Tumor suppressor ARF

    PubMed Central

    Través, Paqui G.; Luque, Alfonso; Hortelano, Sonsoles

    2012-01-01

    ARF (alternative reading frame) is one of the most important tumor regulator playing critical roles in controlling tumor initiation and progression. Recently, we have demonstrated a novel and unexpected role for ARF as modulator of inflammatory responses. PMID:23162766

  10. Children's Brain Tumor Foundation

    MedlinePlus

    ... CBTF Justin's Hope Fund Grant Recipients Grants Children’s Brain Tumor Foundation, A non-profit organization, was founded ... and the long term outlook for children with brain and spinal cord tumors through research, support, education, ...

  11. Pediatric Brain Tumor Foundation

    MedlinePlus

    ... you insights into your child's treatment. LEARN MORE Brain tumors and their treatment can be deadly so ... Cancer Foundation joins the PBTF Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  12. American Brain Tumor Association

    MedlinePlus

    ... in the Ear Canals Read More ABTA News October 5, 2016 Largest American Brain Tumor Association Team Running in Bank of America Chicago Marathon Sunday, October 9 September 21, 2016 American Brain Tumor Association Awards 16 Grants to Support ...

  13. Lung Carcinoid Tumor: Surgery

    MedlinePlus

    ... for lung carcinoid tumor symptoms Surgery to treat lung carcinoid tumors Surgery is the main treatment for ... often be cured by surgery alone. Types of lung surgery Different operations can be used to treat ( ...

  14. Labial salivary gland tumors.

    PubMed

    Neville, B W; Damm, D D; Weir, J C; Fantasia, J E

    1988-05-15

    A study was conducted on labial salivary gland tumors from four oral pathology laboratories. Of the 103 identified tumors, 87 (84.5%) were from the upper lip, whereas 16 (15.5%) were from the lower lip. Of the 87 upper lip tumors, 80 (92.0%) were benign. Forty-three of these were monomorphic adenomas and 37 were pleomorphic adenomas. Seven malignant tumors of the upper lip were as follows: four adenoid cystic carcinomas, two acinic cell carcinomas, and one adenocarcinoma. Of the 16 lower lip tumors, 15 (93.8%) were malignant. Thirteen of these were mucoepidermoid carcinomas and two were acinic cell carcinomas. The only benign lower lip tumor was an intraductal papilloma. These results confirm the findings of previous investigations, showing that minor salivary gland tumors are much more common in the upper lip than the lower lip, but that lower lip tumors are more likely to be malignant.

  15. Metrological scanning probe microscope

    NASA Astrophysics Data System (ADS)

    Dorozhovets, N.; Hausotte, T.; Manske, E.; Jäger, G.; Hofmann, N.

    2006-04-01

    Today's technological progress calls for metrologically accurate object measurement, positioning and scanning with nanometre precision and over large measuring ranges. In order to meet that requirement a nanopositioning and nanomeasuring machine (NPM machine) was developed at the Institute of Process Measurement and Sensor Technology of the Technische Universitaet Ilmenau. This device is capable of highly exact long-range positioning and measurement of objects with a resolution of less than 0.1 nm. Due to the structure of the machine many different probe systems can be installed, including scanning probe microscopes (SPMs). A few SPMs have outstanding metrological characteristics and many commercial microscopes only perform as image acquisition tools. Commercial SPMs use piezoelectric actuators in order to move either the sample or the probe. The position measurement sometimes results from the applied voltage to the piezoelectric actuators or from the strain gauge or capacitive displacement sensor data. This means that they suffer from hysteresis, creep, nonlinear characteristics and Abbe offsets. For an accurate measurement the position of the cantilever must be measured in addition to the torsion and bending. The best solution is a combined detection system with a single laser beam. This system has been realized with a special interferometer system, in which the measuring beam is focused on the cantilever backside using a lens. The reflected beam is split with a part being detected by a quadrant photo-diode and the other part being fed back into the interferometer for position measurement. The quadrant photo-diode is used to detect the cantilever torsion and bending.

  16. [Intrapulmonary Solitary Fibrous Tumor].

    PubMed

    Komori, Kazuyuki; Tabata, Toshiharu; Katsumata, Hiroshi; Minowa, Muneo; Fujimura, Shigefumi

    2015-08-01

    We report a case of intrapulmonary solitary fibrous tumor( SFT). A 34-year-old woman was referred to our hospital due to an abnormal shadow on a chest roentgenogram without symptom. Computed tomography showed a circumscribed intrapulmonary tumor with mild uptake on fluorodeoxyglucose (FDG)-positron emission tomography( PET) in the left lower lobe( S6). Frozen examination revealed a mesenchymal tumor. Based on the pathological and immunohistochemical findings, the tumor was diagnosed as intrapulmonary SFT.

  17. [Intrapulmonary Solitary Fibrous Tumor].

    PubMed

    Komori, Kazuyuki; Tabata, Toshiharu; Katsumata, Hiroshi; Minowa, Muneo; Fujimura, Shigefumi

    2015-08-01

    We report a case of intrapulmonary solitary fibrous tumor( SFT). A 34-year-old woman was referred to our hospital due to an abnormal shadow on a chest roentgenogram without symptom. Computed tomography showed a circumscribed intrapulmonary tumor with mild uptake on fluorodeoxyglucose (FDG)-positron emission tomography( PET) in the left lower lobe( S6). Frozen examination revealed a mesenchymal tumor. Based on the pathological and immunohistochemical findings, the tumor was diagnosed as intrapulmonary SFT. PMID:26329708

  18. Vacuum probe surface sampler

    NASA Technical Reports Server (NTRS)

    Zahlava, B. A. (Inventor)

    1973-01-01

    A vacuum probe surface sampler is described for rapidly sampling relatively large surface areas which possess relatively light loading densities of micro-organism, drug particles or the like. A vacuum head with a hollow handle connected to a suitable vacuum source is frictionally attached to a cone assembly terminating in a flared tip adapted to be passed over the surface to be sampled. A fine mesh screen carried by the vacuum head provides support for a membrane filter which collects the microorganisms or other particles. The head assembly is easily removed from the cone assembly without contacting the cone assembly with human hands.

  19. Experimental probes of axions

    SciTech Connect

    Chou, Aaron S.; /Fermilab

    2009-10-01

    Experimental searches for axions or axion-like particles rely on semiclassical phenomena resulting from the postulated coupling of the axion to two photons. Sensitive probes of the extremely small coupling constant can be made by exploiting familiar, coherent electromagnetic laboratory techniques, including resonant enhancement of transitions using microwave and optical cavities, Bragg scattering, and coherent photon-axion oscillations. The axion beam may either be astrophysical in origin as in the case of dark matter axion searches and solar axion searches, or created in the laboratory from laser interactions with magnetic fields. This note is meant to be a sampling of recent experimental results.

  20. Atom Probe Tomography 2012

    NASA Astrophysics Data System (ADS)

    Kelly, Thomas F.; Larson, David J.

    2012-08-01

    In the world of tomographic imaging, atom probe tomography (APT) occupies the high-spatial-resolution end of the spectrum. It is highly complementary to electron tomography and is applicable to a wide range of materials. The current state of APT is reviewed. Emphasis is placed on applications and data analysis as they apply to many fields of research and development including metals, semiconductors, ceramics, and organic materials. We also provide a brief review of the history and the instrumentation associated with APT and an assessment of the existing challenges in the field.

  1. What Is Wilms Tumor?

    MedlinePlus

    ... tumor): In these tumors, the look of the cancer cells varies widely, and the cells’ nuclei (the central parts that contain the DNA) tend to be very large and distorted. This is called anaplasia . The more anaplasia a tumor has, the harder it is to cure. Other types of kidney cancers in children Most ...

  2. Brain and Spinal Tumors

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Brain and Spinal Tumors Information Page Synonym(s): Spinal Cord ... en Español Additional resources from MedlinePlus What are Brain and Spinal Tumors? Tumors of the brain and ...

  3. Recurrent mixed tumor.

    PubMed

    Batsakis, J G

    1986-01-01

    Recurrence of benign neoplasms can usually be attributed to incomplete excision. Such is the case with benign mixed tumors of salivary glands. Certain histopathologic features of mixed tumors, however, appear to facilitate recurrences. These are: a predominantly myxoid composition, and transcapsular extension by the tumor. Multicentric origin is possible, but it must be regarded as a much lower order of probability.

  4. Enzymatic activatable self-assembled peptide nanowire for targeted therapy and fluorescence imaging of tumors.

    PubMed

    Tang, Ying; Wu, Zhan; Zhang, Chong-Hua; Zhang, Xiao-Li; Jiang, Jian-Hui

    2016-03-01

    We developed novel activatable probe using self-assembled peptide nanowires with low affinity and toxicity to tumor cells in the absence of matrix metalloproteinase that showed activated high affinity and toxicity and provided a highly selective and efficient platform for targeted therapy and tumor imaging. PMID:26854263

  5. Optically measured microvascular blood flow contrast of malignant breast tumors.

    PubMed

    Choe, Regine; Putt, Mary E; Carlile, Peter M; Durduran, Turgut; Giammarco, Joseph M; Busch, David R; Jung, Ki Won; Czerniecki, Brian J; Tchou, Julia; Feldman, Michael D; Mies, Carolyn; Rosen, Mark A; Schnall, Mitchell D; DeMichele, Angela; Yodh, Arjun G

    2014-01-01

    Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS), a near-infrared optical method that quantifies deep tissue microvascular blood flow. Tumor-to-normal perfusion ratios are derived from thirty-two human subjects. Mean (95% confidence interval) tumor-to-normal ratio using surrounding normal tissue was 2.25 (1.92-2.63); tumor-to-normal ratio using normal tissues at the corresponding tumor location in the contralateral breast was 2.27 (1.94-2.66), and using normal tissue in the contralateral breast was 2.27 (1.90-2.70). Thus, the mean tumor-to-normal ratios were significantly different from unity irrespective of the normal tissue chosen, implying that tumors have significantly higher blood flow than normal tissues. Therefore, the study demonstrates existence of breast cancer contrast in blood flow measured by DCS. The new, optically accessible cancer contrast holds potential for cancer detection and therapy monitoring applications, and it is likely to be especially useful when combined with diffuse optical spectroscopy/tomography. PMID:24967878

  6. Catabolism of (64)Cu and Cy5.5-labeled human serum albumin in a tumor xenograft model.

    PubMed

    Kang, Choong Mo; Kim, Hyunjung; Koo, Hyun-Jung; Park, Jin Won; An, Gwang Il; Choi, Joon Young; Lee, Kyung-Han; Kim, Byung-Tae; Choe, Yearn Seong

    2016-07-01

    Human serum albumin (HSA), the most abundant protein in blood plasma, has been used as a drug carrier for the last few decades. Residualizingly radiolabeled serum albumin has been reported to be avidly taken up by tumors of sarcoma-bearing mice and to most likely undergo lysosomal degradation. In this study, we prepared (64)Cu-1,4,7,10-tetraazacyclododecane-N,N',N″,N'″-tetraacetic acid (DOTA) and Cy5.5-conjugated HSA (dual probe), and evaluated its tumor uptake and catabolism. Two dual probes were prepared using different DOTA conjugation sites of HSA (one via Lys residues and the other via the Cys residue). (64)Cu-DOTA-Lys-HSA-Cy5.5 (dual probe-Lys) exhibited higher uptake by RR1022 sarcoma cells in vitro than (64)Cu-DOTA-Cys-HSA-Cy5.5 (dual probe-Cys). In RR1022 tumor-bearing mice, the two dual probes showed a similar level of tumor uptake, but uptake of dual probe-Lys was reduced in the liver and spleen compared to dual probe-Cys, probably because of the presence of a higher number of DOTA molecules in the former. At 24 and 48 h after injection, dual probe-Lys was intact or partially degraded in blood, liver, kidney, and tumor samples, but (64)Cu-DOTA-Lys was observed in the urine using radioactivity detection. Similarly, Cy5.5-Lys was observed in the urine using fluorescence detection. These results indicate that dual probe-Lys may be useful for predicting the catabolic fate of drug-HSA conjugates. PMID:27098932

  7. Design of a rectal probe for diffuse optical spectroscopy imaging for chemotherapy and radiotherapy monitoring

    NASA Astrophysics Data System (ADS)

    van de Giessen, Martijn; Santoro, Ylenia; Mirzaei Zarandi, Soroush; Pigazzi, Alessio; Cerussi, Albert E.; Tromberg, Bruce J.

    2014-03-01

    Diffuse optical spectroscopy imaging (DOSI) has shown great potential for the early detection of non-responding tumors during neoadjuvant chemotherapy in breast cancer, already one day after therapy starts. Patients with rectal cancer receive similar chemotherapy treatment. The rectum geometry and tissue properties of healthy and tumor tissue in the rectum and the requirement of surface contact impose constraints on the probe design. In this work we present the design of a DOSI probe with the aim of early chemotherapy/radiotherapy effectiveness detection in rectal tumors. We show using Monte Carlo simulations and phantom measurements that the colon tissue can be characterized reliably using a source-detector separation in the order of 10 mm. We present a design and rapid prototype of a probe for DOSI measurements that can be mounted on a standard laparoscope and that fits through a standard rectoscope. Using predominantly clinically approved components we aim at fast clinical translation.

  8. Chalcogen and pnicogen bonds in complexes of neutral icosahedral and bicapped square-antiprismatic heteroboranes.

    PubMed

    Pecina, Adam; Lepšík, Martin; Hnyk, Drahomír; Hobza, Pavel; Fanfrlík, Jindřich

    2015-02-26

    A systematic quantum mechanical study of σ-hole (chalcogen, pnicogen, and halogen) bonding in neutral experimentally known closo-heteroboranes is performed. Chalcogens and pnicogens are incorporated in the borane cage, whereas halogens are considered as exo-substituents of dicarbaboranes. The chalcogen and pnicogen atoms in the heteroborane cages have partial positive charge and thus more positive σ-holes. Consequently, these heteroboranes form very strong chalcogen and pnicogen bonds. Halogen atoms in dicarbaboranes also have a highly positive σ-hole, but only in the case of C-bonded halogen atoms. In such cases, the halogen bond of heteroboranes is also strong and comparable to halogen bonds in organic compounds with several electron-withdrawing groups being close to the halogen atom involved in the halogen bond.

  9. Fiber optic current probe

    NASA Astrophysics Data System (ADS)

    Wyntjes, G.; Fox, R.

    1984-02-01

    This report documents the results of Phase 1 research into a new type of Fiber Optic Current probe, suitable for high voltage, high current applications. The probe uses a stabilized two frequency HeNe laser to read the magnitude and sign of magnetic field induced circular birefringence in an optical fiber wound around a conductor. Measurements of both alternating and direct currents were demonstrated with a breadboard system. The system was tested at low voltages with currents of up to 4500 amperes peak and with up to 28 turns of optical fiber around the conductor. The response was found to increase linearly with the number of fiber turns. Experimental determinations of the system's frequency response and dynamic range were not possible due to our inability to generate large, fast current transients. The predicted frequency response is 100 kHz with an ability to read transient amplitudes of 300 times the nominal line current. Several single-mode fibers were used to form transducers, and the optimum fiber for further development was identified. The 2-frequency interrogation technique described worked entirely as predicted, and should be applicable to magnetic field measurements in general (i.e., charged particle beams, Tokamaks, antenna patterns, EMP testing, etc.).

  10. Classification of infrared spectra from skin tumors

    NASA Astrophysics Data System (ADS)

    McIntosh, Laura M.; Mansfield, James R.; Crowson, A. Neil; Toole, John W. P.; Mantsch, Henry H.; Jackson, Michael

    2000-05-01

    The clinical differential diagnosis of skin tumors is an often-challenging task, to which the probing of skin with mid- and near-infrared (IR) light may be contributory. The development of objective methods for the analysis of IR spectra remains a major hurdle to developing clinically useful applications. The authors highlight different processing methods for IR spectra from skin biopsies and in-vivo skin tumors. Spectroscopic maps of biopsies of basal cell, squamous cell and melanocytic neoplasms were objectively grouped into distinct clusters that corresponded with tumor, epidermis, dermis, follicle and fat. Normal and abnormal skin components were located within maps using a search engine based upon linear discriminant analysis (LDA). In all instances, areas of tumor were distinct from normal tissue in biopsies. In-vivo, near-IR spectroscopy and LDA allowed discrimination between benign and malignant skin lesions with a high degree of accuracy. We conclude that IR spectroscopy has significant diagnostic promise in the skin cancer arena. The analytical methods described can now be used to create a powerful classification scheme in which to detect skin tumor cells within biopsied and living skin.

  11. Tumor-Penetrating Peptides

    PubMed Central

    Teesalu, Tambet; Sugahara, Kazuki N.; Ruoslahti, Erkki

    2013-01-01

    Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC), contains the integrin-binding RGD motif. RGD mediates tumor-homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR) motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular “zip code” of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies, and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is present in the

  12. Targeting the tumor microenvironment

    PubMed Central

    Bournazou, Eirini; Bromberg, Jacqueline

    2013-01-01

    Persistent JAK-STAT3 signaling is implicated in many aspects of tumorigenesis. Apart from its tumor-intrinsic effects, STAT3 also exerts tumor-extrinsic effects, supporting tumor survival and metastasis. These involve the regulation of paracrine cytokine signaling, alterations in metastatic sites rendering these permissive for the growth of cancer cells and subversion of host immune responses to create an immunosuppressive environment. Targeting this signaling pathway is considered a novel promising therapeutic approach, especially in the context of tumor immunity. In this article, we will review to what extent JAK-STAT3-targeted therapies affect the tumor microenvironment and whether the observed effects underlie responsiveness to therapy. PMID:24058812

  13. Neuroimaging of Spinal Tumors.

    PubMed

    Merhemic, Zulejha; Stosic-Opincal, Tatjana; Thurnher, Majda M

    2016-08-01

    Intradural tumors are relatively rare neoplasms; however, when unrecognized in a timely manner, they can result in serious deficits and disability. These tumors lack obvious clinical symptoms until compression of the cord or neurologic deficits occur. The most common intramedullary lesions are ependymomas, astrocytomas, and hemangioblastomas. Meningiomas and nerve sheath tumors (schwannomas and neurofibromas) comprise most intradural-extramedullary tumors. Less common tumors are hemangiopericytoma, paraganglioma, melanocytoma, melanoma, metastases, and lymphoma. MR imaging is the imaging method of choice, helpful for localization and characterization of these lesions before treatment and for follow-up after treatment. PMID:27417401

  14. Benign ear cyst or tumor

    MedlinePlus

    Osteomas; Exostoses; Tumor - ear; Cysts - ear; Ear cysts; Ear tumors; Bony tumor of the ear canal ... bony tumors of the ear canal (exostoses and osteomas) are caused by excess growth of bone. Repeated ...

  15. Fixture For Calibrating Pressure Probe

    NASA Technical Reports Server (NTRS)

    Ashby, George C., Jr.; Vasquez, Peter; Horsley, Lewis A.; Bowman, John T.; Zumbrun, Henry N.; Eves, John W.

    1994-01-01

    Fixture in form of specially designed clamshell housing enables in situ calibration of pressure transducer mounted in body of pressure probe in wind tunnel. Includes two metal half shells machined with necks and matching cavities, when put together, define larger neck and cavity accommodating probe. Probe secured to bottom half shell by use of clamp before installing top half shell: necessary to follow sequence to protect probe during assembly. Clamshell calibration fixture attached to pressure probe in few minutes, making it possible to calibrate pressure transducer at convenient times. Calibrations performed before and after wind-tunnel runs each day, between runs in event of delays or suspected malfunctions, and essentially any other time, without having to remove probe from wind tunnel.

  16. Tumors of the spine

    PubMed Central

    Ciftdemir, Mert; Kaya, Murat; Selcuk, Esref; Yalniz, Erol

    2016-01-01

    Spine tumors comprise a small percentage of reasons for back pain and other symptoms originating in the spine. The majority of the tumors involving the spinal column are metastases of visceral organ cancers which are mostly seen in older patients. Primary musculoskeletal system sarcomas involving the spinal column are rare. Benign tumors and tumor-like lesions of the musculoskeletal system are mostly seen in young patients and often cause instability and canal compromise. Optimal diagnosis and treatment of spine tumors require a multidisciplinary approach and thorough knowledge of both spine surgery and musculoskeletal tumor surgery. Either primary or metastatic tumors involving the spine are demanding problems in terms of diagnosis and treatment. Spinal instability and neurological compromise are the main and critical problems in patients with tumors of the spinal column. In the past, only a few treatment options aiming short-term control were available for treatment of primary and metastatic spine tumors. Spine surgeons adapted their approach for spine tumors according to orthopaedic oncologic principles in the last 20 years. Advances in imaging, surgical techniques and implant technology resulted in better diagnosis and surgical treatment options, especially for primary tumors. Also, modern chemotherapy drugs and regimens with new radiotherapy and radiosurgery options caused moderate to long-term local and systemic control for even primary sarcomas involving the spinal column. PMID:26925382

  17. [Pediatric retroperitoneal tumors].

    PubMed

    Benicio dos Santos, I; Benicio dos Santos, M

    1980-01-01

    The author has based his work "Retroperitoneals tumors in infancy and childhood" in 65 cases observed at "Hospital Martagao Gesteira", Salvador, Bahia, Brasil. 32 of the retroperitoneals tumors, either intrarenals or extrarenals, observed in infancy and childhood were Wilm's tumor, 22 neuroblastoma, 5 hydronephrosis, 2 multicystic kidney, 1 policystic kidney, 2 pancreatic cyst and 1 biliar cyst. Wilm's tumor had the highest incidence - 32 cases (49,2%); neuroblastoma was in the second place in incidence - 22 (33,8%) of the 65 cases of retroperitoneals tumors studied, were neuroblastoma. As registered by the author in previous paper, the neuroblastoma, on contrary of what is established in the specialized literature, not was: the most frequent abdominal tumors, in infancy and childhood, neither it was also the abdominal pediatric tumor which could match Wilm's tumor in incidence. The plain X ray film of the abdomen, the Excretory Urography, the Cavography and Arteriography, the Radiological Examination of the Stomach and Duodenum, of the Small Intestine and the Colons, contribute in a very important way to establish the topography (retro or intraperitoneal) of the pediatric abdominal tumors. The author emphasizes that the plain X ray film of the abdomen supply important elements for the conclusion concerning the localization of abdominal tumors, from the observation of a simple criterion - the retroperitoneals tumors obliterate the border of kidney, because they are placed in the same plan of the kidney, data which is not pointed out sufficiently by the authors who have studied the subject.

  18. Cartilage-forming tumors.

    PubMed

    Qasem, Shadi A; DeYoung, Barry R

    2014-01-01

    Cartilage-forming tumors as a group are the most common primary bone tumors; this is largely due to the common occurrence of asymptomatic benign lesions such as osteochondroma and enchondroma. The common feature of these tumors is the presence of chondrocytic cells and the formation of cartilaginous tumor matrix. Some of these tumors are true neoplasms while others are hamartomas or developmental abnormalities. The morphologic heterogeneity of these tumors may be explained by a common multipotent mesenchymal cell differentiating along the lines of fetal-adult cartilage maturation. Recently mutations in IDH1 and IDH2 have been detected in a variety of benign and malignant cartilaginous tumors.(1-4.) PMID:24680178

  19. Genital soft tissue tumors.

    PubMed

    Schoolmeester, John K; Fritchie, Karen J

    2015-07-01

    Mesenchymal neoplasms of the vulvovaginal and inguinoscrotal regions are among the most diagnostically challenging specimens in the pathology laboratory owing largely to their unique intersection between general soft tissue tumors and relatively genital-specific mesenchymal tumors. Genital stromal tumors are a unique subset of soft tissue tumors encountered at this location, and this group includes fibroepithelial stromal polyp, superficial (cervicovaginal) myofibroblastoma, cellular angiofibroma, mammary-type myofibroblastoma, angiomyofibroblastoma and aggressive angiomyxoma. Aside from the striking morphologic and immunophenotypic similarity that is seen with these entities, there is evidence that a subset of genital stromal tumors may be linked genetically. This review will focus on simplifying this group of tumors and provide the pathologist or dermatopathologist with practical management information. Smooth muscle tumors of the external genitalia will also be discussed.

  20. Development and application of multiple-probe scanning probe microscopes.

    PubMed

    Nakayama, Tomonobu; Kubo, Osamu; Shingaya, Yoshitaka; Higuchi, Seiji; Hasegawa, Tsuyoshi; Jiang, Chun-Sheng; Okuda, Taichi; Kuwahara, Yuji; Takami, Kazuhiro; Aono, Masakazu

    2012-04-01

    In the research of advanced materials based on nanoscience and nanotechnology, it is often desirable to measure nanoscale local electrical conductivity at a designated position of a given sample. For this purpose, multiple-probe scanning probe microscopes (MP-SPMs), in which two, three or four scanning tunneling microscope (STM) or atomic force microscope (AFM) probes are operated independently, have been developed. Each probe in an MP-SPM is used not only for observing high-resolution STM or AFM images but also for forming an electrical contact enabling nanoscale local electrical conductivity measurement. The world's first double-probe STM (DP-STM) developed by the authors, which was subsequently modified to a triple-probe STM (TP-STM), has been used to measure the conductivities of one-dimensional metal nanowires and carbon nanotubes and also two-dimensional molecular films. A quadruple-probe STM (QP-STM) has also been developed and used to measure the conductivity of two-dimensional molecular films without the ambiguity of contact resistance between the probe and sample. Moreover, a quadruple-probe AFM (QP-AFM) with four conductive tuning-fork-type self-detection force sensing probes has been developed to measure the conductivity of a nanostructure on an insulating substrate. A general-purpose computer software to control four probes at the same time has also been developed and used in the operation of the QP-AFM. These developments and applications of MP-SPMs are reviewed in this paper.

  1. Development and Application of Multiple-Probe Scanning Probe Microscopes

    SciTech Connect

    Nakayama, T.; Kubo, O.; Shingaya, Y.; Higuchi, S.; Hasegawa, T.; Jiang, C. S.; Okuda, T.; Kuwahara, Y.; Takami, K.; Aono, M.

    2012-04-03

    the research of advanced materials based on nanoscience and nanotechnology, it is often desirable to measure nanoscale local electrical conductivity at a designated position of a given sample. For this purpose, multiple-probe scanning probe microscopes (MP-SPMs), in which two, three or four scanning tunneling microscope (STM) or atomic force microscope (AFM) probes are operated independently, have been developed. Each probe in an MP-SPM is used not only for observing high-resolution STM or AFM images but also for forming an electrical contact enabling nanoscale local electrical conductivity measurement. The world's first double-probe STM (DP-STM) developed by the authors, which was subsequently modified to a triple-probe STM (TP-STM), has been used to measure the conductivities of one-dimensional metal nanowires and carbon nanotubes and also two-dimensional molecular films. A quadruple-probe STM (QP-STM) has also been developed and used to measure the conductivity of two-dimensional molecular films without the ambiguity of contact resistance between the probe and sample. Moreover, a quadruple-probe AFM (QP-AFM) with four conductive tuning-fork-type self-detection force sensing probes has been developed to measure the conductivity of a nanostructure on an insulating substrate. A general-purpose computer software to control four probes at the same time has also been developed and used in the operation of the QP-AFM. These developments and applications of MP-SPMs are reviewed in this paper.

  2. Recent patents on imaging nanoprobes for brain tumor diagnosis and therapy.

    PubMed

    Qi, Lifeng; Zheng, Shu; Lin, Biaoyang

    2010-06-01

    Multifunctional nanoprobes, such as nanocrystals, nanoshells, and luminescent nanomaterials, have been developed for imaging biological processes; such as cell signaling, neuroimaging, protein conformation probing, DNA conformation probing, gene transcription, virus infection and replication in cells, protein dynamics, tumor diagnosis, and therapy evaluation. With the application of nanotechnology for CNS-active agents' delivery, nanostructured materials are emerging as a powerful means for diagnosis of CNS disorders, including brain tumors, because of their unique optical size, and surface properties. This review summarizes the recent patents on imaging nanoprobes for brain tumor diagnosis and therapy. The future development in this active cross-disciplinary field will be discussed as well. PMID:20156135

  3. Variable path length spectrophotometric probe

    DOEpatents

    O'Rourke, Patrick E.; McCarty, Jerry E.; Haggard, Ricky A.

    1992-01-01

    A compact, variable pathlength, fiber optic probe for spectrophotometric measurements of fluids in situ. The probe comprises a probe body with a shaft having a polished end penetrating one side of the probe, a pair of optic fibers, parallel and coterminous, entering the probe opposite the reflecting shaft, and a collimating lens to direct light from one of the fibers to the reflecting surface of the shaft and to direct the reflected light to the second optic fiber. The probe body has an inlet and an outlet port to allow the liquid to enter the probe body and pass between the lens and the reflecting surface of the shaft. A linear stepper motor is connected to the shaft to cause the shaft to advance toward or away from the lens in increments so that absorption measurements can be made at each of the incremental steps. The shaft is sealed to the probe body by a bellows seal to allow freedom of movement of the shaft and yet avoid leakage from the interior of the probe.

  4. Multistage Nanoparticles for Improved Delivery into Tumor Tissue

    PubMed Central

    Stylianopoulos, Triantafyllos; Wong, Cliff; Bawendi, Moungi G.; Jain, Rakesh K.; Fukumura, Dai

    2013-01-01

    The enhanced permeability and retention (EPR) effect has been a key rationale for the development of nanoscale carriers to solid tumors. As a consequence of EPR, nanotherapeutics are expected to improve drug and detection probe delivery, have less adverse effects than conventional chemotherapy, and thus result in improved detection and treatment of tumors. Physiological barriers posed by the abnormal tumor microenvironment, however, can hinder the homogeneous delivery of nanomedicine in amounts sufficient to eradicate cancer. To effectively enhance the therapeutic outcome of cancer patients by nanotherapeutics, we have to find ways to overcome these barriers. One possibility is to exploit the abnormal tumor microenvironment for selective and improved delivery of therapeutic agents to tumors. Recently, we proposed a multistage nanoparticle delivery system as a potential means to enable uniform delivery throughout the tumor and improve the efficacy of anticancer therapy. Here, we describe the synthesis of a novel multistage nanoparticle formulation that shrinks in size once it enters the tumor interstitial space to optimize the delivery to tumors as well as within tumors. Finally, we provide detailed experimental methods for the characterization of such nanoparticles. PMID:22449923

  5. Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors

    PubMed Central

    Daldrup-Link, Heike E.; Mohanty, Suchismita; Ansari, Celina; Ito, Ken; Hong, Su Hyun; Hoffmann, Matthias; Pisani, Laura; Boudreau, Nancy; Gambhir, Sanjiv Sam; Coussens, Lisa M.

    2016-01-01

    Limited transendothelial permeability across tumor microvessels represents a significant bottleneck in the development of tumor-specific diagnostic agents and theranostic drugs. Here, we show an approach to increase transendothelial permeability of macromolecular and nanoparticle-based contrast agents via inhibition of the type I TGF-β receptor, activin-like kinase 5 (Alk5), in tumors. Alk5 inhibition significantly increased tumor contrast agent delivery and enhancement on imaging studies, while healthy organs remained relatively unaffected. Imaging data correlated with significantly decreased tumor interstitial fluid pressure, while tumor vascular density remained unchanged. This immediately clinically translatable concept involving Alk5 inhibitor pretreatment prior to an imaging study could be leveraged for improved tumor delivery of macromolecular and nanoparticle-based imaging probes and, thereby, facilitate development of more sensitive imaging tests for cancer diagnosis, enhanced tumor characterization, and personalized, image-guided therapies. PMID:27182558

  6. New probe of naturalness.

    PubMed

    Craig, Nathaniel; Englert, Christoph; McCullough, Matthew

    2013-09-20

    Any new scalar fields that perturbatively solve the hierarchy problem by stabilizing the Higgs boson mass also generate new contributions to the Higgs boson field-strength renormalization, irrespective of their gauge representation. These new contributions are physical, and in explicit models their magnitude can be inferred from the requirement of quadratic divergence cancellation; hence, they are directly related to the resolution of the hierarchy problem. Upon canonically normalizing the Higgs field, these new contributions lead to modifications of Higgs couplings that are typically great enough that the hierarchy problem and the concept of electroweak naturalness can be probed thoroughly within a precision Higgs boson program. Specifically, at a lepton collider this can be achieved through precision measurements of the Higgs boson associated production cross section. This would lead to indirect constraints on perturbative solutions to the hierarchy problem in the broadest sense, even if the relevant new fields are gauge singlets.

  7. Heat transfer probe

    DOEpatents

    Frank, Jeffrey I.; Rosengart, Axel J.; Kasza, Ken; Yu, Wenhua; Chien, Tai-Hsin; Franklin, Jeff

    2006-10-10

    Apparatuses, systems, methods, and computer code for, among other things, monitoring the health of samples such as the brain while providing local cooling or heating. A representative device is a heat transfer probe, which includes an inner channel, a tip, a concentric outer channel, a first temperature sensor, and a second temperature sensor. The inner channel is configured to transport working fluid from an inner inlet to an inner outlet. The tip is configured to receive at least a portion of the working fluid from the inner outlet. The concentric outer channel is configured to transport the working fluid from the inner outlet to an outer outlet. The first temperature sensor is coupled to the tip, and the second temperature sensor spaced apart from the first temperature sensor.

  8. Advanced Langmuir Probe (LP)

    NASA Technical Reports Server (NTRS)

    Voronka, N. R.; Block, B. P.; Carignan, G. R.

    1991-01-01

    The dynamic response of the MK-2 version of the Langmuir probe amplifier was studied. The settling time of the step response is increased by: (1) stray node-to-ground capacitance at series connections between high value feedback resistors; and (2) input capacitance due to the input cable, FET switches, and input source follower. The stray node-to-ground capacitances can be reduced to tolerable levels by elevating the string of feedback resistors above the printing board. A new feedback network was considered, with promising results. The design uses resistances having much lower nominal values, thereby minimizing the effect of stray capacitances. Faster settling times can be achieved by using an operational amplifier having a higher gain-bandwidth product.

  9. Trapping and Probing Antihydrogen

    SciTech Connect

    Wurtele, Jonathan

    2013-03-27

    Precision spectroscopy of antihydrogen is a promising path to sensitive tests of CPT symmetry. The most direct route to achieve this goal is to create and probe antihydrogen in a magnetic minimum trap. Antihydrogen has been synthesized and trapped for 1000s at CERN by the ALPHA Collaboration. Some of the challenges associated with achieving these milestones will be discussed, including mixing cryogenic positron and antiproton plasmas to synthesize antihydrogen with kinetic energy less than the trap potential of .5K. Recent experiments in which hyperfine transitions were resonantly induced with microwaves will be presented. The opportunity for gravitational measurements in traps based on detailed studies of antihydrogen dynamics will be described. The talk will conclude with a discussion future antihydrogen research that will use a new experimental apparatus, ALPHA-I.

  10. Small rocket tornado probe

    SciTech Connect

    Colgate, S.A.

    1982-01-01

    A (less than 1 lb.) paper rock tornado probe was developed and deployed in an attempt to measure the pressure, temperature, ionization, and electric field variations along a trajectory penetrating a tornado funnel. The requirements of weight and materials were set by federal regulations and a one-meter resolution at a penetration velocity of close to Mach 1 was desired. These requirements were achieved by telemetering a strain gage transducer for pressure, micro size thermister and electric field, and ionization sensors via a pulse time telemetry to a receiver on board an aircraft that digitizes a signal and presents it to a Z80 microcomputer for recording on mini-floppy disk. Recording rate was 2 ms for 8 channels of information that also includes telemetry rf field strength, magnetic field for orientation on the rocket, zero reference voltage for the sensor op amps as well as the previously mentioned items also. The absolute pressure was recorded. Tactically, over 120 h were flown in a Cessna 210 in April and May 1981, and one tornado was encountered. Four rockets were fired at this tornado, missed, and there were many equipment problems. The equipment needs to be hardened and engineered to a significant degree, but it is believed that the feasibility of the probe, tactics, and launch platform for future tornado work has been proven. The logistics of thunderstorm chasing from a remote base in New Mexico is a major difficulty and reliability of the equipment another. Over 50 dummy rockets have been fired to prove trajectories, stability, and photographic capability. Over 25 electronically equipped rockets have been fired to prove sensors transmission, breakaway connections, etc. The pressure recovery factor was calibrated in the Air Force Academy blow-down tunnel. There is a need for more refined engineering and more logistic support.

  11. Development of a novel gamma probe for detecting radiation direction

    NASA Astrophysics Data System (ADS)

    Pani, R.; Pellegrini, R.; Cinti, M. N.; Longo, M.; Donnarumma, R.; D'Alessio, A.; Borrazzo, C.; Pergola, A.; Ridolfi, S.; De Vincentis, G.

    2016-01-01

    Spatial localization of radioactive sources is currently a main issue interesting different fields, including nuclear industry, homeland security as well as medical imaging. It is currently achieved using different systems, but the development of technologies for detecting and characterizing radiation is becoming important especially in medical imaging. In this latter field, radiation detection probes have long been used to guide surgery, thanks to their ability to localize and quantify radiopharmaceutical uptake even deep in tissue. Radiolabelled colloid is injected into, or near to, the tumor and the surgeon uses a hand-held radiation detector, the gamma probe, to identify lymph nodes with radiopharmaceutical uptkake. The present work refers to a novel scintigraphic goniometric probe to identify gamma radiation and its direction. The probe incorporates several scintillation crystals joined together in a particular configuration to provide data related to the position of a gamma source. The main technical characteristics of the gamma locator prototype, i.e. sensitivity, spatial resolution and detection efficiency, are investigated. Moreover, the development of a specific procedure applied to the images permits to retrieve the source position with high precision with respect to the currently used gamma probes. The presented device shows a high sensitivity and efficiency to identify gamma radiation taking a short time (from 30 to 60 s). Even though it was designed for applications in radio-guided surgery, it could be used for other purposes, as for example homeland security.

  12. Improved dewpoint-probe calibration

    NASA Technical Reports Server (NTRS)

    Stephenson, J. G.; Theodore, E. A.

    1978-01-01

    Relatively-simple pressure-control apparatus calibrates dewpoint probes considerably faster than conventional methods, with no loss of accuracy. Technique requires only pressure measurement at each calibration point and single absolute-humidity measurement at beginning of run. Several probes can be calibrated simultaneously and points can be checked above room temperature.

  13. Bacteraemia caused by periodontal probing.

    PubMed

    Daly, C; Mitchell, D; Grossberg, D; Highfield, J; Stewart, D

    1997-04-01

    Bacteraemia of oral origin may result in infective endocarditis in susceptible individuals. The aim of this pilot study was to investigate the occurrence of bacteraemia due to periodontal probing. Thirty patients (15 male, 15 female; mean age 42.7 years) with untreated periodontitis were investigated. All were free of significant medical disorders and none had taken antibiotics in the previous month. Prior to and immediately following periodontal probing, 20 mL of venous blood were obtained from each patient and inoculated into aerobic and anaerobic blood culture bottles and incubated. Negative bottles were monitored continuously for three weeks before being discarded. Periodontal probing consisted of measuring pockets at six points around each tooth and recording the presence or absence of bleeding. A positive bacteraemia was recorded for three of the patients prior to probing. One patient exhibited Prevotella species whilst two exhibited skin commensals. Following probing, 13 patients (43 per cent) exhibited bacteraemia of oral origin. Viridans streptococci were the most common isolates (45 per cent). No significant correlations were found between bacteraemia and the severity of periodontitis or extent of bleeding on probing. The results indicate that periodontal probing can cause bacteraemia in patients with periodontitis. It would be advisable for patients considered at risk of developing infective endocarditis to receive antibiotic prophylaxis for periodontal probing if they have radiographic evidence of periodontitis.

  14. Circulating Tumor Cells.

    PubMed

    Paoletti, Costanza; Hayes, Daniel F

    2016-01-01

    Circulating Tumor Cells (CTC) are shed from primary or secondary tumors. Prior studies have demonstrated that enumeration of CTC is a robust independent prognostic factor of progression free and overall survival in patients with early and metastatic breast cancer. CTC, as well as other circulating tumor markers, have the appealing advantages over tissue biopsy of (1) ease of collection, (2) serial evaluation, and (3) interrogation of the entire tumor burden instead of just a limited part of the tumor. Advances have been recently made in phenotyping and genotyping of CTC, which should provide insights into the predictive role of CTC for sensitivity or resistance to therapies. In addition, CTC phenotypic marker changes during the course of treatment may serve as pharmacodynamic monitoring tools. Therefore, CTC may be considered "liquid biopsies," providing prognostic and predictive clinical information as well as additional understanding of tumor heterogeneity.

  15. Water cooled static pressure probe

    NASA Technical Reports Server (NTRS)

    Lagen, Nicholas T. (Inventor); Eves, John W. (Inventor); Reece, Garland D. (Inventor); Geissinger, Steve L. (Inventor)

    1991-01-01

    An improved static pressure probe containing a water cooling mechanism is disclosed. This probe has a hollow interior containing a central coolant tube and multiple individual pressure measurement tubes connected to holes placed on the exterior. Coolant from the central tube symmetrically immerses the interior of the probe, allowing it to sustain high temperature (in the region of 2500 F) supersonic jet flow indefinitely, while still recording accurate pressure data. The coolant exits the probe body by way of a reservoir attached to the aft of the probe. The pressure measurement tubes are joined to a single, larger manifold in the reservoir. This manifold is attached to a pressure transducer that records the average static pressure.

  16. Electrophoresis-mass spectrometry probe

    DOEpatents

    Andresen, Brian D.; Fought, Eric R.

    1987-01-01

    The invention involves a new technique for the separation of complex mixtures of chemicals, which utilizes a unique interface probe for conventional mass spectrometers which allows the electrophoretically separated compounds to be analyzed in real-time by a mass spectrometer. This new chemical analysis interface, which couples electrophoresis with mass spectrometry, allows complex mixtures to be analyzed very rapidly, with much greater specificity, and with greater sensitivity. The interface or probe provides a means whereby large and/or polar molecules in complex mixtures to be completely characterized. The preferred embodiment of the probe utilizes a double capillary tip which allows the probe tip to be continually wetted by the buffer, which provides for increased heat dissipation, and results in a continually operating interface which is more durable and electronically stable than the illustrated single capillary tip probe interface.

  17. Thiol Reactive Probes and Chemosensors

    PubMed Central

    Peng, Hanjing; Chen, Weixuan; Cheng, Yunfeng; Hakuna, Lovemore; Strongin, Robert; Wang, Binghe

    2012-01-01

    Thiols are important molecules in the environment and in biological processes. Cysteine (Cys), homocysteine (Hcy), glutathione (GSH) and hydrogen sulfide (H2S) play critical roles in a variety of physiological and pathological processes. The selective detection of thiols using reaction-based probes and sensors is very important in basic research and in disease diagnosis. This review focuses on the design of fluorescent and colorimetric probes and sensors for thiol detection. Thiol detection methods include probes and labeling agents based on nucleophilic addition and substitution, Michael addition, disulfide bond or Se-N bond cleavage, metal-sulfur interactions and more. Probes for H2S are based on nucleophilic cyclization, reduction and metal sulfide formation. Thiol probe and chemosensor design strategies and mechanism of action are discussed in this review. PMID:23202239

  18. Rotating concave eddy current probe

    DOEpatents

    Roach, Dennis P.; Walkington, Phil; Rackow, Kirk A.; Hohman, Ed

    2008-04-01

    A rotating concave eddy current probe for detecting fatigue cracks hidden from view underneath the head of a raised head fastener, such as a buttonhead-type rivet, used to join together structural skins, such as aluminum aircraft skins. The probe has a recessed concave dimple in its bottom surface that closely conforms to the shape of the raised head. The concave dimple holds the probe in good alignment on top of the rivet while the probe is rotated around the rivet's centerline. One or more magnetic coils are rigidly embedded within the probe's cylindrical body, which is made of a non-conducting material. This design overcomes the inspection impediment associated with widely varying conductivity in fastened joints.

  19. Electrophoresis-mass spectrometry probe

    DOEpatents

    Andresen, B.D.; Fought, E.R.

    1987-11-10

    The invention involves a new technique for the separation of complex mixtures of chemicals, which utilizes a unique interface probe for conventional mass spectrometers which allows the electrophoretically separated compounds to be analyzed in real-time by a mass spectrometer. This new chemical analysis interface, which couples electrophoresis with mass spectrometry, allows complex mixtures to be analyzed very rapidly, with much greater specificity, and with greater sensitivity. The interface or probe provides a means whereby large and/or polar molecules in complex mixtures to be completely characterized. The preferred embodiment of the probe utilizes a double capillary tip which allows the probe tip to be continually wetted by the buffer, which provides for increased heat dissipation, and results in a continually operating interface which is more durable and electronically stable than the illustrated single capillary tip probe interface. 8 figs.

  20. Anti-tumor immunity generated by photodynamic therapy in a metastatic murine tumor model

    NASA Astrophysics Data System (ADS)

    Castano, Ana P.; Hamblin, Michael R.

    2005-04-01

    Photodynamic therapy (PDT) is a modality for the treatment of cancer involving excitation of photosensitizers with harmless visible light producing reactive oxygen species. The major biological effects of PDT are apoptosis of tumor cells, destruction of the blood supply and activation of the immune system. The objective of this study is to compare in an animal model of metastatic cancer, PDT alone and PDT combined with low-dose cyclophosphamide (CY). Since the tumor we used is highly metastatic, it is necessary to generate anti-tumor immunity using PDT to both cure the primary tumor and prevent death from metastasis. This immunity may be potentiated by low dose CY. In our model we used J774 cells (a Balb/c reticulum cell sarcoma line with the characteristics of macrophages) and the following PDT regimen: benzoporphyrin derivative monoacid ring A (BPD, 2mg/kg injected IV followed after 15 min by 150 J/cm2 of 690-nm light). CY (50 mg/kg i.p.) was injected 48 hours before light delivery. BPD-PDT led to complete regression of the primary tumor in more than half the mice but no permanent cures were obtained. BPD-PDT in combination with CY led to 60% permanent cures. CY alone gave no permanent cures but did provide a survival advantage. To probe permanent immunity cured animals were rechallenged with the same tumor cell line and the tumors were rejected in 71% of mice cured with BPD-PDT plus CY. We conclude that BPD-PDT in combination with CY gives best overall results and that this is attributable to immunological response activation in addition to PDT-mediated destruction of the tumor.

  1. Tumor cell metabolism

    PubMed Central

    Romero-Garcia, Susana; Lopez-Gonzalez, Jose Sullivan; B´ez-Viveros, José Luis; Aguilar-Cazares, Dolores

    2011-01-01

    Cancer is a genetic disease that is caused by mutations in oncogenes, tumor suppressor genes and stability genes. The fact that the metabolism of tumor cells is altered has been known for many years. However, the mechanisms and consequences of metabolic reprogramming have just begun to be understood. In this review, an integral view of tumor cell metabolism is presented, showing how metabolic pathways are reprogrammed to satisfy tumor cell proliferation and survival requirements. In tumor cells, glycolysis is strongly enhanced to fulfill the high ATP demands of these cells; glucose carbons are the main building blocks in fatty acid and nucleotide biosynthesis. Glutaminolysis is also increased to satisfy NADPH regeneration, whereas glutamine carbons replenish the Krebs cycle, which produces metabolites that are constantly used for macromolecular biosynthesis. A characteristic feature of the tumor microenvironment is acidosis, which results from the local increase in lactic acid production by tumor cells. This phenomenon is attributed to the carbons from glutamine and glucose, which are also used for lactic acid production. Lactic acidosis also directs the metabolic reprogramming of tumor cells and serves as an additional selective pressure. Finally, we also discuss the role of mitochondria in supporting tumor cell metabolism. PMID:22057267

  2. [Retroperitoneal germ cell tumor].

    PubMed

    Borrell Palanca, A; García Garzón, J; Villamón Fort, R; Domenech Pérez, C; Martínez Lorente, A; Gunthner, S; García Sisamón, F

    1999-03-01

    We report a case of retroperitoneal extragonadal germ-cell tumor in an 17 years old patient who presented with aedema and pain in left inferior extremity asociated with hemopthysis caused by pulmonar metastasis, who was treated with chemotherapy and resection of residual mass and pulmonary nodes. Dyagnosis was stableshed by fine neadle aspiration biopsy of the wass. We comment on the difficult of stableshing differential dyagnosis between retroperitoneal extragonadal germ-cell tumor and metastasis of a testicular tumor. Dyagnosis is stableshed by the finding of a histologically malignant germ-cell tumor with normal testis. We considered physical examination and ecographyc exploration enough for a correct dyagnosis.

  3. Radioresistance of Brain Tumors

    PubMed Central

    Kelley, Kevin; Knisely, Jonathan; Symons, Marc; Ruggieri, Rosamaria

    2016-01-01

    Radiation therapy (RT) is frequently used as part of the standard of care treatment of the majority of brain tumors. The efficacy of RT is limited by radioresistance and by normal tissue radiation tolerance. This is highlighted in pediatric brain tumors where the use of radiation is limited by the excessive toxicity to the developing brain. For these reasons, radiosensitization of tumor cells would be beneficial. In this review, we focus on radioresistance mechanisms intrinsic to tumor cells. We also evaluate existing approaches to induce radiosensitization and explore future avenues of investigation. PMID:27043632

  4. Tumor Ablation and Nanotechnology

    PubMed Central

    Manthe, Rachel L.; Foy, Susan P.; Krishnamurthy, Nishanth; Sharma, Blanka; Labhasetwar, Vinod

    2010-01-01

    Next to surgical resection, tumor ablation is a commonly used intervention in the treatment of solid tumors. Tumor ablation methods include thermal therapies, photodynamic therapy, and reactive oxygen species (ROS) producing agents. Thermal therapies induce tumor cell death via thermal energy and include radiofrequency, microwave, high intensity focused ultrasound, and cryoablation. Photodynamic therapy and ROS producing agents cause increased oxidative stress in tumor cells leading to apoptosis. While these therapies are safe and viable alternatives when resection of malignancies is not feasible, they do have associated limitations that prevent their widespread use in clinical applications. To improve the efficacy of these treatments, nanoparticles are being studied in combination with nonsurgical ablation regimens. In addition to better thermal effect on tumor ablation, nanoparticles can deliver anticancer therapeutics that show synergistic anti-tumor effect in the presence of heat and can also be imaged to achieve precision in therapy. Understanding the molecular mechanism of nanoparticle-mediated tumor ablation could further help engineer nanoparticles of appropriate composition and properties to synergize the ablation effect. This review aims to explore the various types of nonsurgical tumor ablation methods currently used in cancer treatment and potential improvements by nanotechnology applications. PMID:20866097

  5. Computer assisted biopsy of breast tumors.

    PubMed

    Arambula Cosio, Fernando; Lira Berra, Eric; Hevia Montiel, Nidiyare; Garcia Segundo, Cresencio; Garduno, Edgar; Alvarado Gonzalez, Montserrat; Quispe Siccha, Rosa Ma; Reyes Ramirez, Bartolome; Hazan Lasri, Eric

    2010-01-01

    In this paper we report our preliminary results of the development of a computer assisted system for breast biopsy. The system is based on tracked ultrasound images of the breast. A three dimensional ultrasound volume is constructed from a set of tracked B-scan images acquired with a calibrated probe. The system has been designed to assist a radiologist during breast biopsy, and also as a training system for radiology residents. A semiautomatic classification algorithm was implemented to assist the user with the annotation of the tumor on an ultrasound volume. We report the development of the system prototype, tested on a physical phantom of a breast with a tumor, made of polivinil alcohol. PMID:21097108

  6. Halogen bonding controls selectivity of FRET substrate probes for MMP-9.

    PubMed

    Tranchant, Isabelle; Vera, Laura; Czarny, Bertrand; Amoura, Mehdi; Cassar, Evelyne; Beau, Fabrice; Stura, Enrico A; Dive, Vincent

    2014-03-20

    Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases that catalyze cleavage of extracellular matrix and nonmatrix proteins. MMPs play a role in tissue remodeling, and their uncontrolled activity is associated with number of diseases, including tumor metastasis. Thus, there is a need to develop methods to monitor MMP activity, and number of probes has been previously described. The key problem many probes encounter is the issue of selectivity, since 23 human MMPs, despite playing different physiological roles, have structurally similar active sites. Here, we introduce the halogen bonding concept into the probe design and show that the probe containing iodine exhibits an unprecedented selectivity for MMP-9. We provide structure-based explanation for the selectivity, confirming that it is due to formation of the halogen bond that supports catalysis, and we highlight the value of exploring halogen bonding in the context of selective probe design. PMID:24583051

  7. Gravity Probe B Encapsulated

    NASA Technical Reports Server (NTRS)

    2004-01-01

    In this photo, the Gravity Probe B (GP-B) space vehicle is being encapsulated atop the Delta II launch vehicle. The GP-B is the relativity experiment developed at Stanford University to test two extraordinary predictions of Albert Einstein's general theory of relativity. The experiment will measure, very precisely, the expected tiny changes in the direction of the spin axes of four gyroscopes contained in an Earth-orbiting satellite at a 400-mile altitude. So free are the gyroscopes from disturbance that they will provide an almost perfect space-time reference system. They will measure how space and time are very slightly warped by the presence of the Earth, and, more profoundly, how the Earth's rotation very slightly drags space-time around with it. These effects, though small for the Earth, have far-reaching implications for the nature of matter and the structure of the Universe. GP-B is among the most thoroughly researched programs ever undertaken by NASA. This is the story of a scientific quest in which physicists and engineers have collaborated closely over many years. Inspired by their quest, they have invented a whole range of technologies that are already enlivening other branches of science and engineering. Launched April 20, 2004 , the GP-B program was managed for NASA by the Marshall Space Flight Center. Development of the GP-B is the responsibility of Stanford University along with major subcontractor Lockheed Martin Corporation. (Image credit to Russ Underwood, Lockheed Martin Corporation).

  8. Long duration ash probe

    DOEpatents

    Hurley, J.P.; McCollor, D.P.; Selle, S.J.

    1994-07-26

    A long duration ash probe includes a pressure shell connected to a port in a combustor with a sample coupon mounted on a retractable carriage so as to retract the sample coupon within the pressure shell during soot blowing operation of the combustor. A valve mounted at the forward end of the pressure shell is selectively closeable to seal the sample coupon within the shell, and a heating element in the shell is operable to maintain the desired temperature of the sample coupon while retracted within the shell. The carriage is operably mounted on a pair of rails within the shell for longitudinal movement within the shell. A hollow carrier tube connects the hollow cylindrical sample coupon to the carriage, and extends through the carriage and out the rearward end thereof. Air lines are connected to the rearward end of the carrier tube and are operable to permit coolant to pass through the air lines and thence through the carrier tube to the sample coupon so as to cool the sample coupon. 8 figs.

  9. Long duration ash probe

    DOEpatents

    Hurley, John P.; McCollor, Don P.; Selle, Stanley J.

    1994-01-01

    A long duration ash probe includes a pressure shell connected to a port in a combustor with a sample coupon mounted on a retractable carriage so as to retract the sample coupon within the pressure shell during sootblowing operation of the combustor. A valve mounted at the forward end of the pressure shell is selectively closeable to seal the sample coupon within the shell, and a heating element in the shell is operable to maintain the desired temperature of the sample coupon while retracted within the shell. The carriage is operably mounted on a pair of rails within the shell for longitudinal movement within the shell. A hollow carrier tube connects the hollow cylindrical sample coupon to the carriage, and extends through the carriage and out the rearward end thereof. Air lines are connected to the rearward end of the carrier tube and are operable to permit coolant to pass through the air lines and thence through the carrier tube to the sample coupon so as to cool the sample coupon.

  10. Probing interfaces involving liquids.

    PubMed

    Robinson, A L

    1987-04-10

    Last month in Washington, D.C., the National Academy of Sciences held the first of what it hopes will be a series of seminars in forefront fields of science, technology, and medicine. The idea is to bring the academy closer to the frontlines of research and to help spread the word to federal science policy-makers. The subject of the 23 and 24 March seminar was interfaces and thin films, and the talks, though tutorial in nature, contained a pleasantly large number of still unpublished results. Interfaces, such as the surface of a solid exposed to a liquid or gas, and thin films, whose properties are heavily influenced by interfaces, have long been of considerable technological importance and have always been so in biological processes, but researchers are now getting access to the experimental and theoretical tools needed to explore these complex physical systems that are neither ideally two-dimensional nor fully three-dimensional. The briefings that follow give a peek at three ways to probe interfaces involving liquids.

  11. Selective tumor destruction with photodynamic therapy: exploitation of photodynamic thresholds

    NASA Astrophysics Data System (ADS)

    Barr, Hugh

    1991-11-01

    The uptake and distribution of the photosensitizer aluminum sulphonated phthalocyanine (AlSPc) has been studied. In a variety of experimentally induced gastrointestinal tumors the photosensitizer is retained between 24 - 48 hours after intravenous administration compared with the adjacent normal tissue in which the tumor arose. However, the maximum tumor-to- normal-tissue ratio was only 2:1. Quantitative fluorescence photometry using digital image processing, with a CCD camera and helium neon laser, was used to probe the microscopic localization of the photosensitizer in tissue sections of tumor and normal tissue. Selective localization of the photosensitizer was nonspecific in tumor stroma and there was never any significant difference between normal and neoplastic cells. Exploitation of the small differences in photosensitizer concentration, photodynamic threshold effects, and photosensitizer photodegration allows up to 2 mm of selective tumor damage to be produced in a tumor, when a similar light dose will produce no damage in adjacent normal tissue. However, selective eradication of a tumor without adjacent tissue damage will not be possible by using these methods. This paper reviews this previously reported data.

  12. Fluorescence in situ hybridization testing of chromosomes 6, 8, 9 and 11 in melanocytic tumors is difficult to automate and reveals tumor heterogeneity in melanomas

    PubMed Central

    Uguen, Arnaud; Uguen, Marie; Talagas, Matthieu; Gobin, Eric; Marcorelles, Pascale; De Braekeleer, Marc

    2016-01-01

    Malignant melanomas may be difficult to differentiate from benign nevi on the basis of histology. Contrary to nevi, the majority of melanomas harbor chromosomal imbalances. Comparative genomic hybridization-based and fluorescence in situ hybridization (FISH) tests can help differentiating malignant from benign tumors. In the present study, eight-bacterial artificial chromosome (BAC) probes targeting chromosomes 6, 8, 9 and 11 were tested by FISH, and compared with a commercial four-color FISH probe set targeting chromosomes 6 and 11 in a first set of 62 tissue microarray-included melanocytic tumors (47 melanomas and 15 nevi). A second set of 108 tumors (70 melanomas and 38 nevi) was analyzed with the eight-probes kit, and manual counting was compared with the newly developed automated FISH signals counting and with semi-quantitative visual detection of chromosomal imbalances. Intra-tumor heterogeneity was also evaluated in 12 melanomas and 10 patients with paired melanoma samples. Testing the tumors from the first set with the commercial kit and the eight-probes test permitted to correctly identify 45/47 and 47/47 melanomas, respectively. In the second tumor set, 65/70 malignant tumors presented at least one chromosomal imbalance, whereas none was detected in the nevi. The agreement between manual and automated signals counting was better in good-quality FISH slides compared with poor-quality slides. Semi-quantitative visual appreciation of chromosomal imbalances also reached strong agreement with exact manual counting. In addition, a frequent cytogenetic heterogeneity within melanomas and between paired tumors was noticed in patients with metastatic melanomas. To conclude, FISH testing targeting chromosomes 6, 8, 9 and 11 enabled to differentiate the majority of melanomas from nevi but was difficult to automate. Tumor cytogenetic heterogeneity was frequent and could impair FISH testing. PMID:27698849

  13. Fluorescence in situ hybridization testing of chromosomes 6, 8, 9 and 11 in melanocytic tumors is difficult to automate and reveals tumor heterogeneity in melanomas

    PubMed Central

    Uguen, Arnaud; Uguen, Marie; Talagas, Matthieu; Gobin, Eric; Marcorelles, Pascale; De Braekeleer, Marc

    2016-01-01

    Malignant melanomas may be difficult to differentiate from benign nevi on the basis of histology. Contrary to nevi, the majority of melanomas harbor chromosomal imbalances. Comparative genomic hybridization-based and fluorescence in situ hybridization (FISH) tests can help differentiating malignant from benign tumors. In the present study, eight-bacterial artificial chromosome (BAC) probes targeting chromosomes 6, 8, 9 and 11 were tested by FISH, and compared with a commercial four-color FISH probe set targeting chromosomes 6 and 11 in a first set of 62 tissue microarray-included melanocytic tumors (47 melanomas and 15 nevi). A second set of 108 tumors (70 melanomas and 38 nevi) was analyzed with the eight-probes kit, and manual counting was compared with the newly developed automated FISH signals counting and with semi-quantitative visual detection of chromosomal imbalances. Intra-tumor heterogeneity was also evaluated in 12 melanomas and 10 patients with paired melanoma samples. Testing the tumors from the first set with the commercial kit and the eight-probes test permitted to correctly identify 45/47 and 47/47 melanomas, respectively. In the second tumor set, 65/70 malignant tumors presented at least one chromosomal imbalance, whereas none was detected in the nevi. The agreement between manual and automated signals counting was better in good-quality FISH slides compared with poor-quality slides. Semi-quantitative visual appreciation of chromosomal imbalances also reached strong agreement with exact manual counting. In addition, a frequent cytogenetic heterogeneity within melanomas and between paired tumors was noticed in patients with metastatic melanomas. To conclude, FISH testing targeting chromosomes 6, 8, 9 and 11 enabled to differentiate the majority of melanomas from nevi but was difficult to automate. Tumor cytogenetic heterogeneity was frequent and could impair FISH testing.

  14. Tumor-Targeted Nanomedicines

    PubMed Central

    ElBayoumi, Tamer A.; Torchilin, Vladimir P.

    2009-01-01

    Purpose The efficacy of drug delivery systems can be enhanced by making them target-specific via the attachment of various ligands. We attempted to enhance tumor accumulation and therapeutic effect of doxorubicin-loaded long-circulating PEGylated liposomes (Doxil®, ALZA Corp.) by coupling to their surface the anti-cancer monoclonal antibody 2C5 (mAb 2C5) with nuclesome (NS)-restricted activity, that can recognize the surface of various tumor but not normal cells and specifically targets pharmaceutical carriers to tumor cells in vitro and in vivo. Following earlier in vitro results with various cancer cell lines, the mAb 2C5-liposomes were studied in vivo vs. plain and non-specific IgG-liposomes. Experimental design Antibody coupling to Doxil® was performed via the “post-insertion” technique. Using 111In-labeled liposomes, the tissue biodistribution and pharmacokinetic profile were studied, as well as their accumulation in tumors in mice was followed by the whole-body γ-scintigraphic imaging. Therapeutic efficacy of mAb 2C5-targeted Doxil® vs. non-specific IgG-modified and original Doxil® controls was followed by registering live tumor growth and determining tumor weights upon mice sacrifice. Results mAb2C5 antibody-targeted liposomes demonstrate enhanced accumulation in tumors, and the in vivo therapeutic activity of the mAb 2C5-Doxil® treatment was found to be significantly superior, resulting in final tumor weights of only 25-40% compared to all Doxil® control treatments, when tested against the subcutaneous primary murine tumors of 4T1 and C26 and human PC3 tumor in nude mice. Conclusions Our results demonstrate the remarkable capability of 2C5-targeted Doxil® to specifically deliver its cargo into various tumors significantly increasing the efficacy of therapy. PMID:19276264

  15. Preclinical Molecular Imaging of Tumor Angiogenesis

    PubMed Central

    Zhu, Lei; Niu, Gang; Fang, Xuexun; Chen, Xiaoyuan

    2010-01-01

    Angiogenesis, a course that new blood vessels grow from the existing vasculature, plays important roles both physiologically and pathologically. Angiogenesis can be switched on by growth factors secreted by tumor cells, and in turn supplies more oxygen and nutrition to the tumor. More and more preclinical studies and clinical trials have shown that inhibition of angiogenesis is an effective way to inhibit tumor growth, substantiating the development of anti-angiogenesis therapeutics. Imaging technologies accelerate the translation of preclinical research to the clinic. In oncology, various imaging modalities are widely applied to drug development, tumor early detection and therapy response monitoring. So far, several angiogenesis related imaging agents are promising in cancer diagnosis. However, more effective imaging agents with less side-effect still need to be pursued to visualize angiogenesis process non-invasively. The main purpose of this review is to summarize the recent progresses in preclinical molecular imaging of angiogenesis and to discuss the potential of the current preclinical probes specific to various angiogenesis targets including vascular endothelial growth factor and its receptors (VEGF/VEGFRs), integrin αvβ3 and matrix metalloproteinases (MMPs). It is predicable that related investigations in the field will benefit cancer research and quicken the anti-angiogenic drug development. PMID:20639815

  16. Roles of Tumor Microenvironment in Hepatocelluar Carcinoma

    PubMed Central

    Seo, Haeng R.

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most malignant human cancers, with a high mortality rate worldwide despite its early diagnosis in patients and improvement in therapeutic technology. Most cases of liver cancer show a strong resistance to anticancer therapy. Moreover, liver cancer patients generally have poor tolerance to chemotherapy due to liver dysfunction. In these situations, liver-targeting drugs with fewer side effects and a high efficacy are urgently needed during drug discovery for liver cancer. Researchers have aimed to derive target genes and drug candidates for HCC; however, the development of targeted drugs has not yet improved the outcome significantly. Recently, the role of the tumor microenvironment (TME) in HCC has been probed to combat this deadly disease. A deeper knowledge of the crosstalk between tumor cells and their TME is needed to fully understand tumor development, progression and chemo-resistance in HCC because this cancer develops from chronically damaged tissue that contains large amounts of inflammation and fibrosis. In this review, we summarize how distinct stromal cells of TME are involved in tumorigenesis and chemo-resistance in HCC and the significant challenge to recapitulate tumor complexity and heterogeneity enhancement.

  17. Multiple-measurement beam probe

    SciTech Connect

    Gilpatrick, J.D.; Grant, D.L.

    1986-01-01

    Particle accelerators are becoming smaller and are producing more intense beams; therefore, it is critical that beam-diagnostic instrumentation provide accelerator operators and automated control systems with a complete set of beam information. Traditionally, these beam data were collected and processed using limited-bandwidth interceptive techniques. For the new-generation accelerators, we are developing a multiple-measurement microstrip probe to obtain broadband beam data from inside a drift tube without perturbing the beam. The cylindrical probe's dimensions are 6-cm OD by 1.0 m long, and the probe is mounted inside a drift tube. The probe (and its associated electronics) monitors bunched-beam current, energy, and transverse position by sensing the beam's electromagnetic fields through the annular opening in the drift tube. The electrical impedance is tightly controlled through the full length of the probe and transmission lines to maintain beam-induced signal fidelity. The probe's small, cylindrical structure is matched to beam-bunch characteristics at specific beamline locations so that signal-to-noise ratios are optimized. Surrounding the probe, a mechanical structure attaches to the drift-tube interior and the quadrupole magnets; thus, the entire assembly's mechanical and electrical centers can be aligned and calibrated with respect to the rest of the linac.

  18. Imaging site-specific peptide-targeting in tumor tissues using spectral-domain optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ma, Lixin; Zhang, Miao; Yu, Ping

    2011-03-01

    We report imaging studies on site-specific peptide-targeting in tumor tissues using newly developed optical peptide probes and spectral-domain optical coherence tomography (SD-OCT). The system used two broadband superluminescent light emission diodes with different central wavelengths. An electro-optic modulation in the reference beam was used to get full-range deep imaging inside tumor tissues. The optical probes were based on Bombesin (BBN) that is a fourteen amino acid peptide. BBN has high binding affinity to gastrin-releasing peptide (GRP) receptors overexpressed on several human cancer cell lines. Fluorescence BBN probes were developed by conjugating the last eight residues of BBN, -Q-W-A-V-G-H-L-M-(NH2), with Alexa Flour 680 or Alexa Fluor 750 dye molecules via amino acid linker -G-G-G. The SD-OCT imaging can identify normal tissue and tumor tissue through the difference in scattering coefficient, and trace the BBN conjugate probes through the absorption of the dye molecules using the twowavelength algorithm. We performed the specific uptake and receptor-blocking experiments of the optical BBN probes in severely compromised immunodeficient mouse model bearing human PC-3 prostate tumor xenografts. Tumor and muscle tissues were collected and used for SD-OCT imaging. The SD-OCT images showed fluorescence traces of the BBN probes in the peptide-targeted tumor tissues. Our results demonstrated that SD-OCT is a potential tool for preclinical and clinical early cancer detection.

  19. Benign bone tumors.

    PubMed

    Steffner, Robert

    2014-01-01

    Benign bone lesions are a broad category that demonstrates a spectrum of activities from latent to aggressive. Differentiating the various tumors is important in order to properly determine necessary intervention. This chapter focuses on the presentation, imaging, diagnostic features, and treatment of the most common benign bone tumors in order to help guide diagnosis and management. PMID:25070230

  20. Metastatic pleural tumor

    MedlinePlus

    ... persons. Alternative Names Tumor - metastatic pleural Images Pleural space References Arenberg D, Pickens A. Metastatic malignant tumors. In: Mason RJ, Murray JF, Broaddus VC, et al., eds. Murray and Nadel's Textbook of Respiratory Medicine . 5th ed. Philadelphia, PA: Elsevier Saunders; 2010:chap ...

  1. Skull Base Tumors

    NASA Astrophysics Data System (ADS)

    Schulz-Ertner, Daniela

    In skull base tumors associated with a low radiosensitivity for conventional radiotherapy (RT), irradiation with proton or carbon ion beams facilitates a safe and accurate application of high tumor doses due to the favorable beam localization properties of these particle beams. Cranial nerves, the brain stem and normal brain tissue can at the same time be optimally spared.

  2. [Metachronous bilateral Wilms' tumor].

    PubMed

    Mambié Meléndez, M; Guibelalde Del Castillo, M; Nieto Del Rincón, N; Rodrigo Jiménez, D; Femenia Reus, A; Román Piñana, J M

    2002-03-01

    Wilms' tumor occurs in 5-10 % of all cases of nephroblastoma. The metachronous form represents 2-3 % of cases. Most (96.2 %) metachronous tumors appear within the first 5 years of the primary tumor. Associated malformations are more common in bilateral cases. Metachronous tumors are a therapeutic challenge. We describe the case of an 11-year-old girl with left hemihypertrophy. The diagnosis was metachronous relapse of Wilms' tumor 7 years after the first diagnosis. The patient received five courses of preoperative chemotherapy and tumorectomy was performed. Because of post-surgical complications, nephrectomy was performed on her only kidney. Since she is anephric, the patient is in chronic renal failure and is dependent on dialysis. Treatment with carboplatin and etoposide was continued after surgery and the patient is currently in complete remission. The appearance of a metachronous Wilms' tumor 5 years after that of the primary tumor is rare. When a contralateral tumour develops, chemotherapy must be given until the size of the tumor is reduced in order to preserve renal function and avoid dialysis. In patients with chronic renal failure caused by bilateral nephrectomy, ongoing treatment with dialysis support can be achieved through the choice of effective drugs and knowledge of their pharmacokinetics and pharmacodynamics.

  3. Detecting both melanoma depth and volume in vivo with a handheld photoacoustic probe

    NASA Astrophysics Data System (ADS)

    Zhou, Yong; Li, Guo; Zhu, Liren; Li, Chiye; Cornelius, Lynn A.; Wang, Lihong V.

    2016-03-01

    We applied a linear-array-based photoacoustic probe to detect the tumor depth and volume of melanin-containing melanoma in nude mice in vivo. We demonstrated the ability of this linear-array-based system to measure both the depth and volume of melanoma through phantom, ex vivo, and in vivo experiments. The volume detection ability also enables us to accurately calculate the rate of growth of the tumor, which is important in quantifying tumor activity. Our results show that this system can be used for clinical melanoma diagnosis and treatment at the bedside.

  4. Ways of probing situated concepts.

    PubMed

    Morais, Ana Sofia; Olsson, Henrik; Schooler, Lael J

    2010-02-01

    Two ways of eliciting conceptual content have been to instruct participants to list the intrinsic properties that concept exemplars possess or to report any thoughts that come to mind about the concept. It has been argued that the open, unconstrained probe is better able to elicit the situational information that concepts contain. We evaluated this proposal in two experiments comparing the two probes with regard to the content that they yield for object concepts at the superordinate and basic levels. The results showed that the open probe was better able to elicit situated conceptual knowledge and point out differences in the representations of superordinate and basic concepts.

  5. A subcutaneous Raman needle probe.

    PubMed

    Day, John C C; Stone, Nicholas

    2013-03-01

    Raman spectroscopy is a powerful tool for studying the biochemical composition of tissues and cells in the human body. We describe the initial results of a feasibility study to design and build a miniature, fiber optic probe incorporated into a standard hypodermic needle. This probe is intended for use in optical biopsies of solid tissues to provide valuable information of disease type, such as in the lymphatic system, breast, or prostate, or of such tissue types as muscle, fat, or spinal, when identifying a critical injection site. The optical design and fabrication of this probe is described, and example spectra of various ex vivo samples are shown. PMID:23452501

  6. Saturn orbiter dual probe mission

    NASA Technical Reports Server (NTRS)

    Rudd, R. P.

    1978-01-01

    The described Saturn orbiter dual probe mission and spacecraft combines three systems into a multi-purpose Saturn exploration package. The spacecraft consists of: (1) Saturn orbiter; (2) Saturn probe; and (3) Titan probe or lander. This single spacecraft provides the capability to conduct in situ measurements of the Saturn and Titan atmospheres, and, possibly the Titan surface, as well as a variety of remote sensing measurements. The remote sensing capabilities will be used to study the surfaces, interiors and environments of Saturn's satellites, the rings of Saturn, Saturn's magnetosphere, and synoptic properties of Saturn's atmosphere.

  7. ESA Venus Entry Probe Study

    NASA Technical Reports Server (NTRS)

    vandenBerg, M. L.; Falkner, P.; Phipps, A.; Underwood, J. C.; Lingard, J. S.; Moorhouse, J.; Kraft, S.; Peacock, A.

    2005-01-01

    The Venus Entry Probe is one of ESA s Technology Reference Studies (TRS). The purpose of the Technology Reference Studies is to provide a focus for the development of strategically important technologies that are of likely relevance for future scientific missions. The aim of the Venus Entry Probe TRS is to study approaches for low cost in-situ exploration of Venus and other planetary bodies with a significant atmosphere. In this paper, the mission objectives and an outline of the mission concept of the Venus Entry Probe TRS are presented.

  8. The Huygens Probe System Design

    NASA Astrophysics Data System (ADS)

    Clausen, K. C.; Hassan, H.; Verdant, M.; Couzin, P.; Huttin, G.; Brisson, M.; Sollazzo, C.; Lebreton, J.-P.

    2002-07-01

    The Huygens Probe is the ESA-provided element of the joint NASA/ESA Cassini/Huygens mission to Saturn and its largest moon Titan. Huygens is an entry probe designed to enter Titan's atmosphere and descend under parachute down to the surface. The Probe is carried to Titan on board the Cassini Saturn Orbiter. Huygens is dormant for 7.2 years, during the interplanetary journey and during the first 6 months around Saturn. It is activated about every 6 months for an in-flight checkout to verify and monitor its health and to perform a periodic maintenance and calibration of the payload instruments. The Probe will be targeted to Titan and released from the Orbiter about 3 weeks before the Titan encounter on the third Orbit around Saturn. During the 3-week coast phase the Probe is ‘OFF’, except a timer unit that has the task to awaken Huygens before it enters Titan's atmosphere. The Probe's aeroshell will decelerate it in less than 2 minutes from the entry speed of about 6 km s-1 to 400 m s-1 (Mach 1.5) at an altitude of 150 180 km. From that point onwards, a pre-programmed sequence will trigger the parachute deployment and the heat-shield ejection. The main part of the scientific mission will then start, lasting for a descent of 2 21/2 hours. The Orbiter will listen to the Probe for a total duration of at least 3 hours, which includes time to receive data from the surface, should the Probe continue to transmit data after touchdown. Huygens' transmissions are received and stored aboard the Orbiter for later retransmission to the Earth. This paper presents a technical description of the elements of the Huygens Probe System. The reader is invited to refer to the companion paper (Lebreton and Matson, 2002) for further background information about the Huygens mission, and the payload. The early in-flight performance of the Probe is briefly discussed. During in-flight testing in 2000, a technical anomaly was found with the Probe-to-Orbiter telecommunication system that

  9. Floating Potential Probe Langmuir Probe Data Reduction Results

    NASA Technical Reports Server (NTRS)

    Morton, Thomas L.; Minow, Joseph I.

    2002-01-01

    During its first five months of operations, the Langmuir Probe on the Floating Potential Probe (FPP) obtained data on ionospheric electron densities and temperatures in the ISS orbit. In this paper, the algorithms for data reduction are presented, and comparisons are made of FPP data with ground-based ionosonde and Incoherent Scattering Radar (ISR) results. Implications for ISS operations are detailed, and the need for a permanent FPP on ISS is examined.

  10. Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors.

    PubMed

    Kuo, Lu-Ting; Lu, Hsueh-Yi; Lee, Chien-Chang; Tsai, Jui-Chang; Lai, Hong-Shiee; Tseng, Ham-Min; Kuo, Meng-Fai; Tu, Yong-Kwang

    2016-08-01

    Aberrant methylation has been associated with transcriptional inactivation of tumor-related genes in a wide spectrum of human neoplasms. The influence of DNA methylation in oligodendroglial tumors is not fully understood. Genomic DNA was isolated from 61 oligodendroglial tumors for analysis of methylation using methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). We correlated methylation status with clinicopathological findings and outcome. The genes found to be most frequently methylated in oligodendroglial tumors were RASSF1A (80.3%), CASP8 (70.5%), and CDKN2A (52.5%). Kaplan-Meier survival curve analysis demonstrated longer duration of progression-free survival in patients with 19q loss, aged less than 38 years, and with a proliferative index of less than 5%. Methylation of the ESR1 promoter is significantly associated with shorter duration of overall survival and progression-free survival, and that methylation of IGSF4 and RASSF1A is significantly associated with shorter duration of progression-free survival. However, none of the methylation status of ESR1, IGSF4, and RASSF1A was of prognostic value for survival in a multivariate Cox model. A number of novel and interesting epigenetic alterations were identified in this study. The findings highlight the importance of methylation profiles in oligodendroglial tumors and their possible involvement in tumorigenesis. PMID:27367901

  11. Gravity Probe B Assembled

    NASA Technical Reports Server (NTRS)

    2000-01-01

    In this photo, the Gravity Probe B (GP-B) space vehicle is being assembled at the Sunnyvale, California location of the Lockheed Martin Corporation. The GP-B is the relativity experiment developed at Stanford University to test two extraordinary predictions of Albert Einstein's general theory of relativity. The experiment will measure, very precisely, the expected tiny changes in the direction of the spin axes of four gyroscopes contained in an Earth-orbiting satellite at a 400-mile altitude. So free are the gyroscopes from disturbance that they will provide an almost perfect space-time reference system. They will measure how space and time are very slightly warped by the presence of the Earth, and, more profoundly, how the Earth's rotation very slightly drags space-time around with it. These effects, though small for the Earth, have far-reaching implications for the nature of matter and the structure of the Universe. GP-B is among the most thoroughly researched programs ever undertaken by NASA. This is the story of a scientific quest in which physicists and engineers have collaborated closely over many years. Inspired by their quest, they have invented a whole range of technologies that are already enlivening other branches of science and engineering. Launched April 20, 2004 , the GP-B program was managed for NASA by the Marshall Space Flight Center. Development of the GP-B is the responsibility of Stanford University along with major subcontractor Lockheed Martin Corporation. (Image credit to Russ Underwood, Lockheed Martin Corporation).

  12. Integrated microfluidic probe station

    NASA Astrophysics Data System (ADS)

    Perrault, C. M.; Qasaimeh, M. A.; Brastaviceanu, T.; Anderson, K.; Kabakibo, Y.; Juncker, D.

    2010-11-01

    The microfluidic probe (MFP) consists of a flat, blunt tip with two apertures for the injection and reaspiration of a microjet into a solution—thus hydrodynamically confining the microjet—and is operated atop an inverted microscope that enables live imaging. By scanning across a surface, the microjet can be used for surface processing with the capability of both depositing and removing material; as it operates under immersed conditions, sensitive biological materials and living cells can be processed. During scanning, the MFP is kept immobile and centered over the objective of the inverted microscope, a few micrometers above a substrate that is displaced by moving the microscope stage and that is flushed continuously with the microjet. For consistent and reproducible surface processing, the gap between the MFP and the substrate, the MFP's alignment, the scanning speed, the injection and aspiration flow rates, and the image capture need all to be controlled and synchronized. Here, we present an automated MFP station that integrates all of these functionalities and automates the key operational parameters. A custom software program is used to control an independent motorized Z stage for adjusting the gap, a motorized microscope stage for scanning the substrate, up to 16 syringe pumps for injecting and aspirating fluids, and an inverted fluorescence microscope equipped with a charge-coupled device camera. The parallelism between the MFP and the substrate is adjusted using manual goniometer at the beginning of the experiment. The alignment of the injection and aspiration apertures along the scanning axis is performed using a newly designed MFP screw holder. We illustrate the integrated MFP station by the programmed, automated patterning of fluorescently labeled biotin on a streptavidin-coated surface.

  13. [Circulating "tumor markers" in gastrointestinal tumors].

    PubMed

    Borlinghaus, P; Lamerz, R

    1991-09-01

    Tumor markers (TM) of the neoplastic cell can be divided into non-shedded substances and antigens shedded in blood, urine or other body fluids. For clinicians circulating TM are more important. All relevant circulating TM are not useful in screening of asymptomatic patients because of insufficient sensitivity and specificity. With caution they are useful in the observation of risk groups. Circulating TM have their main significance as additional parameters in monitoring symptomatic patients with malignancies. Several follow up determinations are more important than one single measurement. During follow up of tumor patients TM should not be checked automatically if there are no diagnostic or therapeutical consequences. The clinically most important circulating TM in non-hormone secreting tumors of the gastrointestinal tract are the oncofetal antigens CEA and AFP and antigens defined by monoclonal antibodies e. g. CA 19-9 and CA 72-4. AFP is the primary TM in hepatocellular carcinoma, often elevated in hepatoblastoma and always normal in cholangiocellular carcinoma. CEA is the TM of first choice in patients with colorectal carcinomas and liver metastasis. CA 19-9 is TM of first choice in pancreatic carcinoma and additionally of diagnostic value in cholangiocellular carcinoma and tumors of the bile ducts. In cancer of the stomach CA 19-9 and CEA are secondary TM in combination with CA 72-4 as primary TM. Care should be taken that slight and moderate elevations of TM can be observed in benign diseases of liver, pancreas and bowel.

  14. General Information about Pancreatic Neuroendocrine Tumors (Islet Cell Tumors)

    MedlinePlus

    ... Islet Cell Tumors) Treatment (PDQ®)–Patient Version General Information About Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Go ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  15. Fiberoptic probe and system for spectral measurements

    DOEpatents

    Dai, S.; Young, J.P.

    1998-10-13

    A fused fiberoptic probe, a system, method and embodiments thereof for conducting spectral measurements are disclosed. The fused fiberoptic probe comprises a probe tip having a specific geometrical configuration, an exciting optical fiber and at least one collection optical fiber fused within a housing, preferably silica. The specific geometrical configurations in which the probe tip can be shaped include a slanted probe tip with an angle greater than 0{degree}, an inverted cone-shaped probe tip, and a lens head. 12 figs.

  16. Fiberoptic probe and system for spectral measurements

    DOEpatents

    Dai, Sheng; Young, Jack P.

    1998-01-01

    A fused fiberoptic probe, a system, method and embodiments thereof for conducting spectral measurements are disclosed. The fused fiberoptic probe comprises a probe tip having a specific geometrical configuration, an exciting optical fiber and at least one collection optical fiber fused within a housing, preferrably silica. The specific geometrical configurations in which the probe tip can be shaped include a slanted probe tip with an angle greater than 0.degree., an inverted cone-shaped probe tip, and a lens head.

  17. Modern Brain Tumor Imaging

    PubMed Central

    Barajas, Ramon F.; Cha, Soonmee

    2015-01-01

    The imaging and clinical management of patients with brain tumor continue to evolve over time and now heavily rely on physiologic imaging in addition to high-resolution structural imaging. Imaging remains a powerful noninvasive tool to positively impact the management of patients with brain tumor. This article provides an overview of the current state-of-the art clinical brain tumor imaging. In this review, we discuss general magnetic resonance (MR) imaging methods and their application to the diagnosis of, treatment planning and navigation, and disease monitoring in patients with brain tumor. We review the strengths, limitations, and pitfalls of structural imaging, diffusion-weighted imaging techniques, MR spectroscopy, perfusion imaging, positron emission tomography/MR, and functional imaging. Overall this review provides a basis for understudying the role of modern imaging in the care of brain tumor patients. PMID:25977902

  18. Pediatric genetic ocular tumors

    PubMed Central

    Rouhani, Behnaz; Ramasubramanian, Aparna

    2014-01-01

    Pediatric genetic ocular tumors include malignancies like retinoblastoma and phakomatosis like neurofibromatosis, tuberous sclerosis, von Hippel-Lindau syndrome, and nevoid basal cell carcinoma syndrome. It is important to screen for ocular tumors both for visual prognosis and also for systemic implications. The phakomatosis comprise of multitude of benign tumors that are aysmptomatic but their detection can aid in the diagnosis of the syndrome. Retinoblastoma is the most common malignant intraocular tumor in childhood and with current treatment modalities, the survival is more than 95%. It is transmitted as an autosomal dominant fashion and hence the offsprings of all patients with the germline retinoblastoma need to be screened from birth. This review discusses the various pediatric genetic ocular tumors discussing the clinical manifestation, diagnosis and treatment.

  19. Nanotechnology and tumor microcirculation.

    PubMed

    Kano, Mitsunobu R

    2014-07-01

    Though much progress has been made in the development of anti-tumor chemotherapeutic agents, refractoriness is still a major clinical difficulty because little is known about the non-autonomous mechanisms involved. Abnormal capillary structures in tumors, for example, are well documented, but a thorough characterization of microcirculation, including functional consequences with particular regard to drug delivery and intratumor accumulation, is still required for many kinds of tumor. In this review, we highlight how use of synthesized nanoparticles, themselves a product of emerging nanotechnology, are beginning to open up new perspectives in understanding the functional and therapeutic consequences of capillary structure within tumors. Furthermore, nanoparticles promise exciting new clinical applications. I also stress the urgent necessity of developing clinically relevant tumor models, both in vivo and in vitro.

  20. Zebrafish Germ Cell Tumors.

    PubMed

    Sanchez, Angelica; Amatruda, James F

    2016-01-01

    Germ cell tumors (GCTs) are malignant cancers that arise from embryonic precursors known as Primordial Germ Cells. GCTs occur in neonates, children, adolescents and young adults and can occur in the testis, the ovary or extragonadal sites. Because GCTs arise from pluripotent cells, the tumors can exhibit a wide range of different histologies. Current cisplatin-based combination therapies cures most patients, however at the cost of significant toxicity to normal tissues. While GWAS studies and genomic analysis of human GCTs have uncovered somatic mutations and loci that might confer tumor susceptibility, little is still known about the exact mechanisms that drive tumor development, and animal models that faithfully recapitulate all the different GCT subtypes are lacking. Here, we summarize current understanding of germline development in humans and zebrafish, describe the biology of human germ cell tumors, and discuss progress and prospects for zebrafish GCT models that may contribute to better understanding of human GCTs. PMID:27165367

  1. Method of treating tumors

    DOEpatents

    DeNardo, Sally J.; Burke, Patricia A.; DeNardo, Gerald L.; Goodman, Simon; Matzku, legal representative, Kerstin; Matzku, Siegfried

    2006-04-18

    A method of treating tumors, such as prostate tumors, breast tumors, non-Hodgkin's lymphoma, and the like, includes the sequential steps of administering to the patient at least one dose of an antiangiogenic cyclo-arginine-glycine-aspartic acid-containing pentapeptide (cRGD pentapeptide); administering to the patient an anti-tumor effective amount of a radioimmunotherapeutic agent (RIT); and then administering to the patient at least one additional dose of cRGD pentapeptide. The cRGD pentapeptide is preferably cyclo-(Arg-Gly-Asp-D-Phe-[N-Me]-Val), and the RIT is preferably a radionuclide-labeled chelating agent-ligand complex in which chelating agent is chemically bonded to a tumor-targeting molecule, such as a monoclonal antibody.

  2. Pediatric genetic ocular tumors.

    PubMed

    Rouhani, Behnaz; Ramasubramanian, Aparna

    2014-12-01

    Pediatric genetic ocular tumors include malignancies like retinoblastoma and phakomatosis like neurofibromatosis, tuberous sclerosis, von Hippel-Lindau syndrome, and nevoid basal cell carcinoma syndrome. It is important to screen for ocular tumors both for visual prognosis and also for systemic implications. The phakomatosis comprise of multitude of benign tumors that are aysmptomatic but their detection can aid in the diagnosis of the syndrome. Retinoblastoma is the most common malignant intraocular tumor in childhood and with current treatment modalities, the survival is more than 95%. It is transmitted as an autosomal dominant fashion and hence the offsprings of all patients with the germline retinoblastoma need to be screened from birth. This review discusses the various pediatric genetic ocular tumors discussing the clinical manifestation, diagnosis and treatment. PMID:27625882

  3. Acetate dependence of tumors.

    PubMed

    Comerford, Sarah A; Huang, Zhiguang; Du, Xinlin; Wang, Yun; Cai, Ling; Witkiewicz, Agnes K; Walters, Holly; Tantawy, Mohammed N; Fu, Allie; Manning, H Charles; Horton, Jay D; Hammer, Robert E; McKnight, Steven L; Tu, Benjamin P

    2014-12-18

    Acetyl-CoA represents a central node of carbon metabolism that plays a key role in bioenergetics, cell proliferation, and the regulation of gene expression. Highly glycolytic or hypoxic tumors must produce sufficient quantities of this metabolite to support cell growth and survival under nutrient-limiting conditions. Here, we show that the nucleocytosolic acetyl-CoA synthetase enzyme, ACSS2, supplies a key source of acetyl-CoA for tumors by capturing acetate as a carbon source. Despite exhibiting no gross deficits in growth or development, adult mice lacking ACSS2 exhibit a significant reduction in tumor burden in two different models of hepatocellular carcinoma. ACSS2 is expressed in a large proportion of human tumors, and its activity is responsible for the majority of cellular acetate uptake into both lipids and histones. These observations may qualify ACSS2 as a targetable metabolic vulnerability of a wide spectrum of tumors.

  4. Parotid tumors in children.

    PubMed

    Jaques, D A; Krolls, S O; Chambers, R G

    1976-10-01

    Most salivary gland tumors, both benign and malignant, develop within the parotid glands. Although an overwhelming majority of tumors are reported in the adult population, the parotid glands are also the most frequently involved salivary glands in the pediatric age group. This study represents a combination of case material from the Armed Forces Institute of Pathology and our personal experiences. Of approximately 10,000 salivary gland lesions accessioned in all ages, only 124 tumors occurred in the parotid gland in children less than fifteen years old. There were ninety benign and thirty-four malignant lesions. The two most common benign masses were mixed tumors and vascular lesions. The most common malignancies were the mucoepidermoid and acinic cell carcinomas. We recommended that all solid tumors be removed by parotidectomy.

  5. Sensitive and selective tumor imaging with novel and highly activatable fluorescence strategies

    NASA Astrophysics Data System (ADS)

    Urano, Yasuteru

    2008-02-01

    Nowadays, several tumor imaging modalities such as MRI, PET and fluorescence imaging techniques have been extensively investigated. One of the central problems associated with these conventional tumor-targeted imaging methods, however, is the fact that the signal contrast between tumor and surrounding tissues relies on the efficient targeting to the tumor and the rapid sequestration or excretion of unbound agent. Among these modalities, only fluorescence imaging technique has a significant feature, in that great signal activation could be achieved which potentially leads to the selective imaging of cancer with higher tumor-to-background ratio. In this symposium, I will present some examples of fluorescence cancer imaging based on highly activatable strategies with using precisely designed novel fluorescence probes. Recently, we developed highly sensitive fluorescence probes for β-galactosidase which is applicable for living cell system. By utilizing these probes, we could establish a novel and highly activatable strategy for sensitive and selective optical imaging of imbedded tumor in the peritoneum. We took a two step procedure in that a lectin is used to localize β-galactosidase to cancer cells as an activating enzyme, and subsequent administration of a highly-sensitive fluorescence probe for the enzyme have afforded remarkable fluorescence activation selectively in tumor mass. Since the tumor-targeted enzyme can catalyze numerous substrate turnovers, a great number of fluorescent molecules could be produced and hence the rapid and sensitive detection of tumor in vivo with high tumor-to-background ratio could be achieved. Moreover, the consequent close-up investigation using fluorescence microscopy revealed that cancer microfoci as small as 200 μm could be successfully visualized.

  6. Fluorine-18-fluorodeoxygglucose-guided breast cancer surgery with a positron-sensitive probe: Validation in preclinical studies

    SciTech Connect

    Raylman, R.R.; Fisher, S.J.; Brown, R.S.; Ethier, S.P.; Wahl, R.L.

    1995-10-01

    In this study, the feasibility of utilizing 2-deoxy-2-fluoro-d-glucose (FDG) in conjunction with a positron-sensitive intraoperative probe to guide breast tumor excision was investigated. The probe was constructed with a plastic scintillator tip coupled to a photomultiplier tube with fiber optic cable. Anticipated resolution degradation was evaluated by measurement of line spread functions in the presence of background radiation. Realistic photon background distributions were simulated with a human torso phantom and a cardiac insert. The relationship between resolution and energy threshold was measured to find the optimal discriminator settings. In addition, probe sensitivity as a function of energy threshold was determined for various size-simulated tumors. Finally, the ability to localize breast cancers in vivo was tested in a rodent model. Mammary rat tumors implanted in Lewis rats were examined after injection with FDG; these results were correlated with those of histologic analyses. Measurements of line spread functions indicated that resolution could be maximized in a realistic background photon environment by increasing the energy threshold to levels at or above the Compton continuum edge (340 keV). At this setting, the probe`s sensitivity was determined to be 58 and 11 cps/{mu}Ci for 3.18- and 6.35-mm diameter simulated tumors, respectively. Probe readings correlated well with histologic results; the probe was generally able to discriminate between tumor and normal tissue. This study indicates that breast cancer surgery guided by a positron-sensitive probe warrants future evaluation in breast-conserving surgery of patients with breast cancer. 23 refs., 5 figs.

  7. Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice

    NASA Astrophysics Data System (ADS)

    Patwardhan, Sachin V.; Bloch, Sharon R.; Achilefu, Samuel; Culver, Joseph P.

    2005-04-01

    We present a fast scanning fluorescence optical tomography system for imaging the kinetics of probe distributions through out the whole body of small animals. Configured in a plane parallel geometry, the system scans a source laser using a galvanometer mirror pair (τswitch~1ms) over flexible source patterns, and detects excitation and emission light using a high frame rate low noise, 5 MHz electron multiplied charge-coupled device (EMCCD) camera. Phantom studies were used to evaluate resolution, linearity, and sensitivity. Time dependent (δt=2.2 min.) in vivo imaging of mice was performed following injections of a fluorescing probe (indocyanine green). The capability to detect differences in probe delivery route was demonstrated by comparing an intravenous injection, versus an injection into a fat pocket (retro orbital injection). Feasibility of imaging the distribution of tumor-targeted molecular probes was demonstrated by imaging a breast tumor-specific near infrared polypeptide in MDA MB 361 tumor bearing nude mice. A tomography scan, at 24 hour post injection, revealed preferential uptake in the tumor relative to surrounding tissue.

  8. Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice.

    PubMed

    Patwardhan, Sachin; Bloch, Sharon; Achilefu, Samuel; Culver, Joseph

    2005-04-01

    We present a fast scanning fluorescence optical tomography system for imaging the kinetics of probe distributions through out the whole body of small animals. Configured in a plane parallel geometry, the system scans a source laser using a galvanometer mirror pair (tauswitch~1ms) over flexible source patterns, and detects excitation and emission light using a high frame rate low noise, 5 MHz electron multiplied charge-coupled device (EMCCD) camera. Phantom studies were used to evaluate resolution, linearity, and sensitivity. Time dependent (deltat=2.2 min.) in vivo imaging of mice was performed following injections of a fluorescing probe (indocyanine green). The capability to detect differences in probe delivery route was demonstrated by comparing an intravenous injection, versus an injection into a fat pocket (retro orbital injection). Feasibility of imaging the distribution of tumor-targeted molecular probes was demonstrated by imaging a breast tumor-specific near infrared polypeptide in MDA MB 361 tumor bearing nude mice. A tomography scan, at 24 hour post injection, revealed preferential uptake in the tumor relative to surrounding tissue. PMID:19495147

  9. The Radiation Belt Storm Probes

    NASA Video Gallery

    The Radiation Belt Storm Probe mission (RBSP) will explore the Van Allen Radiation Belts in the Earth's magnetosphere. The charge particles in these regions can be hazardous to both spacecraft and ...

  10. A three dimensional probe positionera)

    NASA Astrophysics Data System (ADS)

    Intrator, T.; Sun, X.; Dorf, L.; Furno, I.; Lapenta, G.

    2008-10-01

    In order to sort out the physics that is important in many plasma experiments, data in three dimensions (3D) are becoming necessary. Access to the usual cylindrical vacuum vessel is typically restricted to radially or axially insertable probes that can pivot. The space that can be explored usually has significant restrictions either because probe travel must be along a travel path, or a "wobbly" probe positioner requires one to map between a moveable coordinate system and a preferred laboratory coordinate system. This could for example introduce errors in measurements of vector quantities such as magnetic field or flow. We describe the design and implementation of a 3D probe positioner that slides in two dimensions on a double O-ring seal and radially inserts along the third dimension. The net result is that a 3D space can be explored in a laboratory Cartesian reference frame.

  11. A three dimensional probe positioner.

    PubMed

    Intrator, T; Sun, X; Dorf, L; Furno, I; Lapenta, G

    2008-10-01

    In order to sort out the physics that is important in many plasma experiments, data in three dimensions (3D) are becoming necessary. Access to the usual cylindrical vacuum vessel is typically restricted to radially or axially insertable probes that can pivot. The space that can be explored usually has significant restrictions either because probe travel must be along a travel path, or a "wobbly" probe positioner requires one to map between a moveable coordinate system and a preferred laboratory coordinate system. This could for example introduce errors in measurements of vector quantities such as magnetic field or flow. We describe the design and implementation of a 3D probe positioner that slides in two dimensions on a double O-ring seal and radially inserts along the third dimension. The net result is that a 3D space can be explored in a laboratory Cartesian reference frame.

  12. Micromachined probes for laboratory plasmas

    NASA Astrophysics Data System (ADS)

    Chiang, Franklin Changta

    As we begin to find more applications for plasmas in our everyday lives, the ability to characterize and understand their inner workings becomes increasingly important. Much of our current understanding of plasma physics comes from investigations conducted in diffuse, outer space plasmas where experimenters have no control over the environment or experimental conditions and one measures interesting phenomena only by chance when the spacecraft or satellite passes through them. Ideally, experiments should be performed in a controlled environment, where plasma events can be deliberately and reliably created when wanted and probes placed precisely within the plasma. Unfortunately, often due to their size, probes used in outer space are unsuitable for use in high-density laboratory plasmas, and constructing probes that can be used in terrestrial plasmas is a considerable challenge. This dissertation presents the development, implementation, and experimental results of three micromachined probes capable of measuring voltage and electric field, ion energies, and changing magnetic fields (B-dot) in laboratory plasmas.

  13. Monitoring probe for groundwater flow

    DOEpatents

    Looney, B.B.; Ballard, S.

    1994-08-23

    A monitoring probe for detecting groundwater migration is disclosed. The monitor features a cylinder made of a permeable membrane carrying an array of electrical conductivity sensors on its outer surface. The cylinder is filled with a fluid that has a conductivity different than the groundwater. The probe is placed in the ground at an area of interest to be monitored. The fluid, typically saltwater, diffuses through the permeable membrane into the groundwater. The flow of groundwater passing around the permeable membrane walls of the cylinder carries the conductive fluid in the same general direction and distorts the conductivity field measured by the sensors. The degree of distortion from top to bottom and around the probe is precisely related to the vertical and horizontal flow rates, respectively. The electrical conductivities measured by the sensors about the outer surface of the probe are analyzed to determine the rate and direction of the groundwater flow. 4 figs.

  14. Monitoring probe for groundwater flow

    DOEpatents

    Looney, Brian B.; Ballard, Sanford

    1994-01-01

    A monitoring probe for detecting groundwater migration. The monitor features a cylinder made of a permeable membrane carrying an array of electrical conductivity sensors on its outer surface. The cylinder is filled with a fluid that has a conductivity different than the groundwater. The probe is placed in the ground at an area of interest to be monitored. The fluid, typically saltwater, diffuses through the permeable membrane into the groundwater. The flow of groundwater passing around the permeable membrane walls of the cylinder carries the conductive fluid in the same general direction and distorts the conductivity field measured by the sensors. The degree of distortion from top to bottom and around the probe is precisely related to the vertical and horizontal flow rates, respectively. The electrical conductivities measured by the sensors about the outer surface of the probe are analyzed to determine the rate and direction of the groundwater flow.

  15. A three dimensional probe positioner

    SciTech Connect

    Intrator, T.; Sun, X.; Furno, I.; Dorf, L.; Lapenta, G.

    2008-10-15

    In order to sort out the physics that is important in many plasma experiments, data in three dimensions (3D) are becoming necessary. Access to the usual cylindrical vacuum vessel is typically restricted to radially or axially insertable probes that can pivot. The space that can be explored usually has significant restrictions either because probe travel must be along a travel path, or a 'wobbly' probe positioner requires one to map between a moveable coordinate system and a preferred laboratory coordinate system. This could for example introduce errors in measurements of vector quantities such as magnetic field or flow. We describe the design and implementation of a 3D probe positioner that slides in two dimensions on a double O-ring seal and radially inserts along the third dimension. The net result is that a 3D space can be explored in a laboratory Cartesian reference frame.

  16. Study of alternative probe technologies

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A number of implied technologies for a deep probe mission was examined; i.e., one that would provide the capability to scientifically examine planetary atmospheres at the 1000 bar level. Conditions imposed by current Jupiter, Saturn, and Uranus atmospheric models were considered. The major thrust of the measurements was to determine lower atmosphere composition, even to trace constituents of one part per billion. Two types of instruments having the necessary accuracy to meet the science objectives were considered and integrated into a deep probe configuration. One deep probe option that resulted was identified as a Minimum Technology Development approach. The significant feature of this option is that only three technology developments are required to enable the mission, i.e., (1) science instrument development, (2) advanced data processing, and (3) external high pressure/thermal insulation. It is concluded that a probe designed for a Jupiter mission could, with minor changes, be used for a Saturn or Uranus mission.

  17. THE TUMOR MACROENVIRONMENT: CANCER-PROMOTING NETWORKS BEYOND TUMOR BEDS

    PubMed Central

    Rutkowski, Melanie R.; Svoronos, Nikolaos; Puchalt, Alfredo Perales; Conejo-Garcia, Jose R.

    2015-01-01

    During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, and myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. PMID:26216635

  18. DNA probe for lactobacillus delbrueckii

    SciTech Connect

    Delley, M.; Mollet, B.; Hottinger, H. )

    1990-06-01

    From a genomic DNA library of Lactobacillus delbrueckii subsp. bulgaricus, a clone was isolated which complements a leucine auxotrophy of an Escherichia coli strain (GE891). Subsequent analysis of the clone indicated that it could serve as a specific DNA probe. Dot-blot hybridizations with over 40 different Lactobacillus strains showed that this clone specifically recognized L. delbrueckii subsp. delbrueckii, bulgaricus, and lactis. The sensitivity of the method was tested by using an {alpha}-{sup 32}P-labeled probe.

  19. The navigation of space probes

    NASA Technical Reports Server (NTRS)

    Fliegel, H. F.; Ohandley, D. A.; Zielenbach, J. W.

    1974-01-01

    A new navigational method combining electronic measurement procedures and celestial mechanics makes it possible to conduct a space probe very close to a desired point in the neighborhood of a remote planet. Approaches for the determination of the position of the space probe in space are discussed, giving attention to the effects of errors in the employed data. The application of the navigational methods in a number of space missions is also considered.

  20. Rapid sensitive analysis of IDH1 mutation in lower-grade gliomas by automated genetic typing involving a quenching probe.

    PubMed

    Kurimoto, Michihiro; Suzuki, Hiromichi; Aoki, Kosuke; Ohka, Fumiharu; Kondo, Goro; Motomura, Kazuya; Iijima, Kentaro; Yamamichi, Akane; Ranjit, Melissa; Wakabayashi, Toshihiko; Kimura, Shinya; Natsume, Atsushi

    2016-01-01

    The authors recently found that 80% of lower-grade gliomas (LGGs) harbored a mutation in IDH1. Intraoperative detection of the mutated IDH1 helps not only differentiate LGGs from other type of brain tumors, but determine the resection border. In the current study, the authors have applied an automated genetic typing involving a quenching probe to detect the mutated IDH1. If tumor cells with the mutated IDH1 contained 10% or more in the mixture of normal and tumor cells, the device could detect it sensitively. The intraoperative assessment of IDH1 mutation is useful in brain tumor surgeries.

  1. Radiology of the spine: Tumors

    SciTech Connect

    Jeanmart, L.

    1986-01-01

    This book deals with tumors of the spinal cord and various aspects of primary and secondary osseous tumors of the spine. Included in discussion are tumors, chordoma hemangioma, vascular malformation and the terms angioma and hemangiomas.

  2. Design and performance of a positron-sensitive surgical probe

    NASA Astrophysics Data System (ADS)

    Liu, Fang

    We report the design and performance of a portable positron-sensitive surgical imaging probe. The probe is designed to be sensitive to positrons and capable of rejecting background gammas including 511 keV. The probe consists of a multi-anode PMT and an 8 x 8 array of thin 2 mm x 2 mm plastic scintillators coupled 1:1 to GSO crystals. The probe uses three selection criteria to identify positrons. An energy threshold on the plastic signals reduces the false positron signals in the plastic due to background gammas; a second energy threshold on the PMT sum signal greatly reduces background gammas in the GSO. Finally, a timing window accepts only 511 keV gammas from the GSO that arrive within 15 ns of the plastic signals, reducing accidental coincidences to a negligible level. The first application being investigated is sentinel lymph node (SLN) surgery, to identify in real-time the location of SLNs in the axilla with high 18F-FDG uptake, which may indicate metastasis. Our simulations and measurements show that the probe's pixel separation ability in terms of peak-to-valley ratio is ˜3.5. The performance measurements also show that the 64-pixel probe has a sensitivity of 4.7 kcps/muCi using optimal signal selection criteria. For example, it is able to detect in 10 seconds a ˜4 mm lesion with a true-to-background ratio of ˜3 at a tumor uptake ratio of ˜8:1. The signal selection criteria can be fine-tuned, either for higher sensitivity, or for a higher image contrast.

  3. Temperature Correction in Probe Measurements

    NASA Astrophysics Data System (ADS)

    Gutsev, S. A.

    2015-09-01

    This work is devoted to experimental investigations of a decaying plasma using Langmuir probes. The gas pressure, the discharge current, and the moment of afterglow were selected to obtain probe characteristics in collisionless, intermediate, and drifting regimes of motion of charged particles. The manner in which the shape of the volt- ampere characteristics changes on passage from the collisionless motion to diffusion motion has been shown. A detailed analysis has been made of the source of errors arising when orbital-motion formulas or the logarithmic-operation method are applied to processing of the probe curves. It has been shown that neglect of collisions of charged particles in the probe layer leads to an ion-density value overstated more than three times, an electron-temperature value overstated two times, and an ion temperature overstated three to nine times. A model of interaction of charged particles in the probe layer has been proposed for correction of the procedure of determining temperature. Such an approach makes it possible to determine the space-charge layer in the probe, and also the value of the self-consistent field. The use of the developed procedures gives good agreement between experimental and theoretical results.

  4. Benign follicular tumors*

    PubMed Central

    Tellechea, Oscar; Cardoso, José Carlos; Reis, José Pedro; Ramos, Leonor; Gameiro, Ana Rita; Coutinho, Inês; Baptista, António Poiares

    2015-01-01

    Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients. PMID:26734858

  5. Automated genotyping of circulating tumor cells.

    PubMed

    Stakenborg, Tim; Liu, Chengxun; Henry, Olivier; Borgen, Elin; Laddach, Nadja; Roeser, Tina; Ritzi-Lehnert, Marion; Fermér, Christian; Hauch, Sigfried; O'Sullivan, Ciara K; Lagae, Liesbet

    2010-09-01

    Cancer remains a prominent health concern in modern societies. Continuous innovations and introduction of new technologies are essential to level or reduce current healthcare spending. A diagnostic platform to detect circulating tumor cells (CTCs) in peripheral blood may be most promising in this respect. CTCs have been proposed as a minimally invasive, prognostic and predictive marker to reflect the biological characteristics of tumors and are implemented in an increasing number of clinical studies. Still, their detection remains a challenge as they may occur at concentrations below one single cell per ml of blood. To facilitate their detection, here we describe microfluidic modules to isolate and genotype CTCs directly from clinical blood samples. In a first cell isolation and detection module, the CTCs are immunomagnetically enriched, separated and counted. In a second module and after cell lysis, the mRNA is reversely transcripted to cDNA, followed by a multiplex ligation probe amplification of 20 specific genetic markers and two control fragments. Following the multiplex ligation probe amplification reaction, the amplified fragments are electrochemically detected in a third and final module. Besides the design of the modules, their functionality is described using control samples. Further testing using clinical samples and integration of all modules in a single, fully automated smart miniaturized system will enable minimal invasive testing for frequent detection and characterization of CTCs.

  6. Aptamers: versatile molecular recognition probes for cancer detection

    PubMed Central

    Sun, Hongguang; Tan, Weihong; Zu, Youli

    2015-01-01

    In the past two decades, aptamers have emerged as a novel class of molecular recognition probes comprising uniquely-folded short RNA or single-stranded DNA oligonucleotides that bind to their cognate targets with high specificity and affinity. Aptamers, often referred to as “chemical antibodies”, possess several highly desirable features for clinical use. They can be chemically synthesized and are easily conjugated to a wide range of reporters for different applications, and are able to rapidly penetrate tissues. These advantages significantly enhance their clinical applicability, and render them excellent alternatives to antibody-based probes in cancer diagnostics and therapeutics. Aptamer probes based on fluorescence, colorimetry, magnetism, electrochemistry, and in conjunction with nanomaterials (e.g., nanoparticles, quantum dots, single-walled carbon nanotubes, and magnetic nanoparticles) have provided novel ultrasensitive cancer diagnostic strategies and assays. Furthermore, promising aptamer targeted-multimodal tumor imaging probes have been recently developed in conjunction with fluorescence, positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). The capabilities of the aptamer-based platforms described herein underscore the great potential they hold for the future of cancer detection. In this review, we highlight the most prominent recent developments in this rapidly advancing field. PMID:26618445

  7. Targeting the tumor microenvironment

    SciTech Connect

    Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

    2006-11-07

    Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

  8. Multiple granular cell tumor.

    PubMed

    Jones, J K; Kuo, T T; Griffiths, C M; Itharat, S

    1980-10-01

    Eleven cases of granular cell tumor were reviewed. In two of the cases multiple sites of involvement were seen. The tumor occurred in the oral cavity in both of these cases and each was initially wrongly diagnosed as squamous cell carcinoma. The most common site was the subcutaneous tissue (nine patients) and the tongue was involved in three cases. In one patient the parotid gland was involved. Eight of the patients were females and three were males; seven were black and four were white. The importance of differentiating between squamous cell carcinoma and granular cell tumor is stressed, as is the need for a simple wide surgical excision. PMID:7421377

  9. Myoepithelial Tumors: An Update.

    PubMed

    Jo, Vickie Y

    2015-09-01

    Primary myoepithelial neoplasms of soft tissue are uncommon, and have been increasingly characterized by clinicopathologic and genetic means. Tumors are classified as mixed tumor/chondroid syringoma, myoepithelioma, and myoepithelial carcinoma, and they share morphologic, immunophenotypic, and genetic features with their salivary gland counterparts. However, soft tissue myoepithelial tumors are classified as malignant based on the presence of cytologic atypia, in contrast to the criterion of invasive growth in salivary gland sites. This review discusses the clinicopathologic and morphologic characteristics, distinct variants, and currently known genetic alterations of myoepithelial neoplasms of soft tissue, skin, and bone.

  10. Multimodality stereotactic brain tissue identification: the NASA smart probe project

    NASA Technical Reports Server (NTRS)

    Andrews, R.; Mah, R.; Aghevli, A.; Freitas, K.; Galvagni, A.; Guerrero, M.; Papsin, R.; Reed, C.; Stassinopoulos, D.

    1999-01-01

    Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of 'optical biopsy' by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2. 7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures. Copyright 2000 S. Karger AG, Basel.

  11. Pazopanib Hydrochloride in Treating Patients With Progressive Carcinoid Tumors

    ClinicalTrials.gov

    2016-11-04

    Atypical Carcinoid Tumor; Foregut Carcinoid Tumor; Hindgut Carcinoid Tumor; Lung Carcinoid Tumor; Metastatic Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Midgut Carcinoid Tumor; Recurrent Digestive System Neuroendocrine Tumor G1; Regional Digestive System Neuroendocrine Tumor G1

  12. Data Mining Empowers the Generation of a Novel Class of Chromosome-specific DNA Probes

    SciTech Connect

    Zeng, Hui; Weier, Heinz-Ulrich G.; Kwan, Johnson; Wang, Mei; O'Brien, Benjamin

    2011-03-08

    Probes that allow accurate delineation of chromosome-specific DNA sequences in interphase or metaphase cell nuclei have become important clinical tools that deliver life-saving information about the gender or chromosomal make-up of a product of conception or the probability of an embryo to implant, as well as the definition of tumor-specific genetic signatures. Often such highly specific DNA probes are proprietary in nature and have been the result of extensive probe selection and optimization procedures. We describe a novel approach that eliminates costly and time consuming probe selection and testing by applying data mining and common bioinformatics tools. Similar to a rational drug design process in which drug-protein interactions are modeled in the computer, the rational probe design described here uses a set of criteria and publicly available bioinformatics software to select the desired probe molecules from libraries comprised of hundreds of thousands of probe molecules. Examples describe the selection of DNA probes for the human X and Y chromosomes, both with unprecedented performance, but in a similar fashion, this approach can be applied to other chromosomes or species.

  13. Fluoromodule-based reporter/probes designed for in vivo fluorescence imaging

    PubMed Central

    Zhang, Ming; Chakraborty, Subhasish K.; Sampath, Padma; Rojas, Juan J.; Hou, Weizhou; Saurabh, Saumya; Thorne, Steve H.; Bruchez, Marcel P.; Waggoner, Alan S.

    2015-01-01

    Optical imaging of whole, living animals has proven to be a powerful tool in multiple areas of preclinical research and has allowed noninvasive monitoring of immune responses, tumor and pathogen growth, and treatment responses in longitudinal studies. However, fluorescence-based studies in animals are challenging because tissue absorbs and autofluoresces strongly in the visible light spectrum. These optical properties drive development and use of fluorescent labels that absorb and emit at longer wavelengths. Here, we present a far-red absorbing fluoromodule–based reporter/probe system and show that this system can be used for imaging in living mice. The probe we developed is a fluorogenic dye called SC1 that is dark in solution but highly fluorescent when bound to its cognate reporter, Mars1. The reporter/probe complex, or fluoromodule, produced peak emission near 730 nm. Mars1 was able to bind a variety of structurally similar probes that differ in color and membrane permeability. We demonstrated that a tool kit of multiple probes can be used to label extracellular and intracellular reporter–tagged receptor pools with 2 colors. Imaging studies may benefit from this far-red excited reporter/probe system, which features tight coupling between probe fluorescence and reporter binding and offers the option of using an expandable family of fluorogenic probes with a single reporter gene. PMID:26348895

  14. Neurosurgical hand-held optical coherence tomography (OCT) forward-viewing probe

    NASA Astrophysics Data System (ADS)

    Sun, Cuiru; Lee, Kenneth K. C.; Vuong, Barry; Cusimano, Michael; Brukson, Alexander; Mariampillai, Adrian; Standish, Beau A.; Yang, Victor X. D.

    2012-02-01

    A prototype neurosurgical hand-held optical coherence tomography (OCT) imaging probe has been developed to provide micron resolution cross-sectional images of subsurface tissue during open surgery. This new ergonomic hand-held probe has been designed based on our group's previous work on electrostatically driven optical fibers. It has been packaged into a catheter probe in the familiar form factor of the clinically accepted Bayonet shaped neurosurgical non-imaging Doppler ultrasound probes. The optical design was optimized using ZEMAX simulation. Optical properties of the probe were tested to yield an ~20 um spot size, 5 mm working distance and a 3.5 mm field of view. The scan frequency can be increased or decreased by changing the applied voltage. Typically a scan frequency of less than 60Hz is chosen to keep the applied voltage to less than 2000V. The axial resolution of the probe was ~15 um (in air) as determined by the OCT system. A custom-triggering methodology has been developed to provide continuous stable imaging, which is crucial for clinical utility. Feasibility of this probe, in combination with a 1310 nm swept source OCT system was tested and images are presented to highlight the usefulness of such a forward viewing handheld OCT imaging probe. Knowledge gained from this research will lay the foundation for developing new OCT technologies for endovascular management of cerebral aneurysms and transsphenoidal neuroendoscopic treatment of pituitary tumors.

  15. Ozone Therapy for Tumor Oxygenation: a Pilot Study

    PubMed Central

    2004-01-01

    Tumor hypoxia is an adverse factor for chemotherapy and radiotherapy. Ozone therapy is a non-conventional form of medicine that has been used successfully in the treatment of ischemic disorders. This prospective study was designed to assess the effect of ozone therapy on tumor oxygenation. Eighteen subjects were recruited for the study. Systemic ozone therapy was administered by autohemotransfusion on three alternate days over one week. Tumor oxygenation levels were measured using polarographic needle probes before and after the first and the third ozone therapy session. Overall, no statistically significant change was observed in the tumor oxygenation in the 18 patients. However, a significant decrease was observed in hypoxic values ≤10 and ≤5 mmHg of pO2. When individually assessed, a significant and inverse non-linear correlation was observed between increase in oxygenation and the initial tumor pO2 values at each measuring time-point, thus indicating that the more poorly-oxygenated tumors benefited most (rho = −0.725; P = 0.001). Additionally, the effect of ozone therapy was found to be lower in patients with higher hemoglobin concentrations (rho = −0.531; P < 0.034). Despite being administered over a very short period, ozone therapy improved oxygenation in the most hypoxic tumors. Ozone therapy as adjuvant in chemo-radiotherapy warrants further research. PMID:15257330

  16. A fiber-optically coupled positron-sensitive surgical probe

    SciTech Connect

    Raylman, R.R.; Wahl, R.L.

    1994-05-01

    Positron-emitting radiopharmaceuticals such as {sup 18}F-labeled 2-deoxy-D-glucose (FDG) have considerable utility in the noninvasive imaging of cancers due to their rapid and excellent tumor-localizing properties. In addition, the relatively short range of positrons in tissue facilitates the precise delineation of FDG-avid tumors. Therefore, FDG used in conjunction with a positron-sensitive probe may be capable of guiding surgical procedures. Many of the current probe systems, however, are sensitive to the intense flux of background photons produced by positron annihilation. The authors describe the design, manufacture and initial in vitro and in vivo testing of a probe well-suited to the detection of positron-emitting isotopes in a high-photon background. The device consists of a small piece of plastic scintillator coupled by fiber-optic cable to a photomultiplier tube. Measurements of resolution and detector sensitivity were obtained. In addition, the reduction in resolution caused by the effects of various levels of background photon flux was determined. These measurements indicate that resolution is degraded minimally ({approximately}5% with a background-to-source ratio of 2:1) due to annihilation photon background. Sensitivity for positrons is good, detecting amounts of radioactivity as low as 10.2 nCi of FDG in vitro. In rats given FDG subcutaneously, lymph nodes containing as little as 11 nCi of FDG could be detected above the background activity levels present in normal surrounding tissues. A plastic scintillator probe system has been devised which may be highly suitable for intraoperative FDG-guided (or other positron or beta emitting-tracer) surgery. 29 refs., 7 figs.

  17. Gene expression and hormone autonomy in radiation-induced tumors of Arabidopsis thaliana

    SciTech Connect

    Persinger, S.M.; Town, C.D. )

    1989-04-01

    In order to study the molecular genetics of factor controlling plant cell growth, we have isolated a group of radiation-induced tumors from Arabidopsis thaliana. Tumors appeared on plants derived from {sup 60}Co gamma-irradiated seed or seedlings, and are capable of hormone-autonomous growth in culture. We have used vertebrate oncogene probes to explore the hypothesis that the tumors arose by the radiation-induced activation of growth-regulating plant oncogenes. One probe, int-2, was used to isolate cDNA clones representing an mRNA differentially expressed between tumors and hormone-dependent callus tissue. The genomic organization and function of this and other differentially expressed Arabidopsis sequences are being further characterized. A second area of study concerns the hormonal status of individual tumors. Tumor tissue varies in color, texture, and degree of differentiation: while some tumors appear undifferentiated, one consistently produces roots, and others occasionally develop shoots or leaflets. The tumors have characteristic growth rates on hormone-free medium, and growth in response to exogenous hormones differs among the tumors themselves and from wild-type. Characterization of the relationships between hormonal status, morphogenesis, and gene expression should yield valuable insights into the mechanisms regulating plant growth and development.

  18. Multi-Color Spectral Transcript Analysis (SPECTRA) for Phenotypic Characterization of Tumor Cells

    PubMed Central

    Hsu, Joanne H.; Weier, Jingly F.; Weier, Heinz-Ulrich G.; Ito, Yuko

    2013-01-01

    Many human tumors show significant changes in their signal transduction pathways and, thus, the way the cells interact with their environment. Often caused by chromosomal rearrangements, including gene amplifications, translocations or deletions, the altered levels of gene expression may provide a tumor-specific signature that can be exploited for diagnostic or therapeutic purposes. We investigated the utility of multiplexed fluorescence in situ hybridization (FISH) using non-isotopically labeled cDNA probes detected by Spectral Imaging as a sensitive and rapid procedure to measure tumor-specific gene expression signatures. We used a commercially available system to acquire and analyze multicolor FISH images. Initial investigations used panels of fluorescent calibration standards to evaluate the system. These experiments were followed by hybridization of five-to-six differently labeled cDNA probes, which target the transcripts of tyrosine kinase genes known to be differently expressed in normal cells and tumors of the breast or thyroid gland. The relatively simple, yet efficient, molecular cytogenetic method presented here may find many applications in characterization of solid tumors or disseminated tumor cells. Addressing tumor heterogeneity by means of multi-parameter single cell analyses is expected to enable a wide range of investigations in the areas of tumor stem cells, tumor clonality and disease progression. PMID:24970164

  19. Effect of reference spectra in spectral fitting to discriminate enzyme-activatable photoacoustic probe from intrinsic optical absorbers

    NASA Astrophysics Data System (ADS)

    Hirasawa, Takeshi; Okawa, Shinpei; Iwatate, Ryu J.; Kamiya, Mako; Urano, Yasuteru; Ishihara, Miya

    2016-03-01

    Multispectral photoacoustic (MS-PA) imaging has been researched to image molecular probes in the presence of strong background signals produced from intrinsic optical absorbers. Spectral fitting method (SFM) discriminates probe signals from background signals by fitting the PA spectra that are calculated from MS-PA images to reference spectra of the probe and background, respectively. Because hemoglobin is a dominant optical absorber in visible to near-infrared wavelength range, absorption spectra of hemoglobin have been widely used as reference background spectra. However, the spectra of background signals produced from heterogeneous biological tissue differ from the reference background spectra due to presence of other intrinsic optical absorbers and effect of optical scattering. Due to the difference, the background signals partly remain in the probe images. To image the probe injected in subcutaneous tumors of mice clearly, we added the melanosome absorption spectrum to the reference background spectra because skin contains nonnegligible concentration of melanosome and the spectrum is very similar to the scattering spectrum of biological tissue. The probe injected in the subcutaneous tumor of mice was an enzyme-activatable probe which show their original colors only in the presence of γ-glutamyltranspeptidase, an enzyme associated with cancer. The probes have been successfully used for rapid fluorescence imaging of cancer. As a result of MS-PA imaging, by considering the melanosome absorption spectrum, the background signals were successfully suppressed and then clearer probe image was obtained. Our MS-PA imaging method afforded successful imaging of tumors in mice injected with activatable PA probes.

  20. Children's Tumor Foundation

    MedlinePlus

    ... The Children’s Tumor Foundation and Vice President Biden’s National Cancer Moonshot Initiative Oct 26, 2016, Posted in Collaborations , Latest News , Press Release , Science Foundation President Annette Bakker Participates in Key Meetings Dedicated ...

  1. Brain tumor - primary - adults

    MedlinePlus

    ... tumor, relieve symptoms, and improve brain function or comfort. Surgery is often needed for most primary brain ... and pressure Anticonvulsants to reduce seizures Pain medicines Comfort measures, safety measures, physical therapy, and occupational therapy ...

  2. Brain tumor - children

    MedlinePlus

    ... symptoms, and improve brain function or the child's comfort. Surgery is needed for most primary brain tumors. ... Anticonvulsants to reduce or prevent seizures Pain medicines Comfort measures, safety measures, physical therapy, occupational therapy, and ...

  3. Solitary fibrous tumor.

    PubMed

    Yilmaz, Cem; Kabatas, Serdar; Ozen, Ozlem Isiksacan; Gulsen, Salih; Caner, Hakan; Altinors, Nur

    2009-12-01

    Intracranial solitary fibrous tumors (SFT) are typically dural based, CD34-positive neoplasms of mesenchymal origin. Since they were first described in 1996 at the meninges, fewer than 100 SFT had been reported in both cranial and spinal compartments of the central nervous system. SFT can resemble other spindle cell tumors both radiologically and histopathologically, and differentiation can be best achieved through viewing their ultrastructure and using immunohistochemical techniques. In this report, we present four patients with SFT. Upon diagnosing two patients with SFT located in the cerebellopontine angle and parasagittal areas, we reviewed our pathological files and found two more patients; one having a parasagittal tumor and the other having a convexity tumor, that had been diagnosed with hemangiopericytoma. These tumours proved to be SFT after an immunohistochemical re-examination.

  4. Skin tumors on squirrels

    USGS Publications Warehouse

    Herman, C.M.; Reilly, J.R.

    1955-01-01

    Skin tumors having the gross appearance of previously reported fibromas are reported on gray squirrels from N. Y., Md., Va., N. C., and W. Va. and from a fox squirrel from W. Va. and a porcupine from Pa.

  5. Dinosaurs Got Tumors, Too

    MedlinePlus

    ... Got Tumors, Too Benign facial growth discovered in fossil dating back about 69 million years To use ... discovery is the first ever described in the fossil record and the first to be thoroughly documented ...

  6. Genetics of adrenal tumors.

    PubMed

    Opocher, G; Schiavi, F; Cicala, M V; Patalano, A; Mariniello, B; Boaretto, F; Zovato, S; Pignataro, V; Macino, B; Negro, I; Mantero, F

    2009-06-01

    The impact of genetics and genomics on clinical medicine is becoming more and more important. Endocrinology pioneered the development of molecular medicine, but also the study of adrenal tumors had a great impact in this field. Particularly important was the detection of genetics of tumors derived from the adrenal medulla, as well as that of those derived from the sympathetic and parasympathetic paraganglia. The identification of mutations in one of the several pheochromocytoma/paraganglioma susceptibility genes may indicate a specific clinical management drive. Less well understood is the genetics of adrenal cortex tumors, in particular adrenocortical carcinoma, a rare and particularly aggressive disease. There are only a few examples of hereditary transmission of adrenocortical carcinoma, but the analysis of low penetrance genes by genome wide association study may enable us to discover new genetic mechanisms responsible for adrenocortical-derived tumors. PMID:19471236

  7. [Regression grading in gastrointestinal tumors].

    PubMed

    Tischoff, I; Tannapfel, A

    2012-02-01

    Preoperative neoadjuvant chemoradiation therapy is a well-established and essential part of the interdisciplinary treatment of gastrointestinal tumors. Neoadjuvant treatment leads to regressive changes in tumors. To evaluate the histological tumor response different scoring systems describing regressive changes are used and known as tumor regression grading. Tumor regression grading is usually based on the presence of residual vital tumor cells in proportion to the total tumor size. Currently, no nationally or internationally accepted grading systems exist. In general, common guidelines should be used in the pathohistological diagnostics of tumors after neoadjuvant therapy. In particularly, the standard tumor grading will be replaced by tumor regression grading. Furthermore, tumors after neoadjuvant treatment are marked with the prefix "y" in the TNM classification. PMID:22293790

  8. Validity of the semi-infinite tumor model in diffuse reflectance spectroscopy for epithelial cancer diagnosis: a Monte Carlo study

    NASA Astrophysics Data System (ADS)

    Zhu, Caigang; Liu, Quan

    2011-08-01

    The accurate understanding of optical properties of human tissues plays an important role in the optical diagnosis of early epithelial cancer. Many inverse models used to determine the optical properties of a tumor have assumed that the tumor was semi-infinite, which infers infinite width and length but finite thickness. However, this simplified assumption could lead to large errors for small tumor, especially at the early stages. We used a modified Monte Carlo code, which is able to simulate light transport in a layered tissue model with buried tumor-like targets, to investigate the validity of the semi-infinite tumor assumption in two common epithelial tissue models: a squamous cell carcinoma (SCC) tissue model and a basal cell carcinoma (BCC) tissue model. The SCC tissue model consisted of three layers, i.e. the top epithelium, the middle tumor and the bottom stroma. The BCC tissue model also consisted of three layers, i.e. the top epidermis, the middle tumor and the bottom dermis. Diffuse reflectance was simulated for two common fiber-optic probes. In one probe, both source and detector fibers were perpendicular to the tissue surface; while in the other, both fibers were tilted at 45 degrees relative to the normal axis of the tissue surface. It was demonstrated that the validity of the semi-infinite tumor model depends on both the fiber-optic probe configuration and the tumor dimensions. Two look-up tables, which relate the validity of the semi-infinite tumor model to the tumor width in terms of the source-detector separation, were derived to guide the selection of appropriate tumor models and fiber optic probe configuration for the optical diagnosis of early epithelial cancers.

  9. Probing the Probes: Fitness Factors For Small Molecule Tools

    PubMed Central

    Workman, Paul; Collins, Ian

    2010-01-01

    Chemical probes for interrogating biological processes are of considerable current interest. Cell permeable small molecule tools have a major role in facilitating the functional annotation of the human genome, understanding both physiological and pathological processes, and validating new molecular targets. To be valuable, chemical tools must satisfy necessary criteria and recent publications have suggested objective guidelines for what makes a useful chemical probe. Although recognizing that such guidelines may be valuable, we caution against overly restrictive rules that may stifle innovation in favor of a “fit-for-purpose” approach. Reviewing the literature and providing examples from the cancer field, we recommend a series of “fitness factors” to be considered when assessing chemical probes. We hope this will encourage innovative chemical biology research while minimizing the generation of poor quality and misleading biological data, thus increasing understanding of the particular biological area, to the benefit of basic research and drug discovery. PMID:20609406

  10. Multiple-probe scanning probe microscopes for nanoarchitectonic materials science

    NASA Astrophysics Data System (ADS)

    Nakayama, Tomonobu; Shingaya, Yoshitaka; Aono, Masakazu

    2016-11-01

    Nanoarchitectonic systems are of interest for utilizing a vast range of nanoscale materials for future applications requiring a huge number of elemental nanocomponents. To explore the science and technology of nanoarchitectonics, advanced characterization tools that can deal with both nanoscale objects and macroscopically extended nanosystems are demanded. Multiple-probe scanning probe microscopes (MP-SPMs) are powerful tools that meet this demand because they take the advantages of conventional scanning probe microscopes and realize atomically precise electrical measurements, which cannot be done with conventional microprobing systems widely used in characterizing materials and devices. Furthermore, an MP-SPM can be used to operate some nanoarchitectonic systems. In this review, we overview the indispensable features of MP-SPMs together with the past, present and future of MP-SPM technology.

  11. Waking up dormant tumors.

    PubMed

    Tse, Joyce C; Kalluri, Raghu

    2011-06-10

    As appreciation grows for the contribution of the tumor microenvironment to the progression of cancer, new evidence accumulates to support that the participation of stromal cells can extend beyond the local environment. Recently, Elkabets and colleagues demonstrated a systemic interaction between cancer cells and distant bone marrow cells to support the growth of otherwise indolent tumor cells at a secondary site, raising thought-provoking questions regarding the involvement of stromal cells in maintaining metastatic dormancy.

  12. Antibody tumor penetration

    PubMed Central

    Thurber, Greg M.; Schmidt, Michael M.; Wittrup, K. Dane

    2009-01-01

    Antibodies have proven to be effective agents in cancer imaging and therapy. One of the major challenges still facing the field is the heterogeneous distribution of these agents in tumors when administered systemically. Large regions of untargeted cells can therefore escape therapy and potentially select for more resistant cells. We present here a summary of theoretical and experimental approaches to analyze and improve antibody penetration in tumor tissue. PMID:18541331

  13. In vivo detection of phospholipase C by enzyme-activated near-infrared probes.

    PubMed

    Mawn, Theresa M; Popov, Anatoliy V; Beardsley, Nancy J; Stefflova, Klara; Milkevitch, Matthew; Zheng, Gang; Delikatny, E James

    2011-12-21

    In this article, the characterization of the first near-infrared (NIR) phospholipase-activated molecular beacon is reported, and its utility for in vivo cancer imaging is demonstrated. The probe consists of three elements: a phospholipid (PL) backbone to which the NIR fluorophore, pyropheophorbide a (Pyro), and the NIR Black Hole Quencher 3 (BHQ) were conjugated. Because of the close proximity of BHQ to Pyro, the Pyro-PtdEtn-BHQ probe is self-quenched until enzyme hydrolysis releases the fluorophore. The Pyro-PtdEtn-BHQ probe is highly specific to one isoform of phospholipase C, phosphatidylcholine-specific phospholipase C (PC-PLC), responsible for catabolizing phosphatidylcholine directly to phosphocholine. Incubation of Pyro-PtdEtn-BHQ in vitro with PC-PLC demonstrated a 150-fold increase in fluorescence that could be inhibited by the specific PC-PLC inhibitor tricyclodecan-9-yl xanthogenate (D609) with an IC(50) of 34 ± 8 μM. Since elevations in phosphocholine have been consistently observed by magnetic resonance spectroscopy in a wide array of cancer cells and solid tumors, we assessed the utility of Pyro-PtdEtn-BHQ as a probe for targeted tumor imaging. Injection of Pyro-PtdEtn-BHQ into mice bearing DU145 human prostate tumor xenografts followed by in vivo NIR imaging resulted in a 4-fold increase in tumor radiance over background and a 2 fold increase in the tumor/muscle ratio. Tumor fluorescence enhancement was inhibited with the administration of D609. The ability to image PC-PLC activity in vivo provides a unique and sensitive method of monitoring one of the critical phospholipase signaling pathways activated in cancer, as well as the phospholipase activities that are altered in response to cancer treatment.

  14. Towards tumor immunodiagnostics

    PubMed Central

    Kotoula, Vassiliki

    2016-01-01

    Immunodiagnostic markers applicable on tissue or cytologic material may be prognostic or predictive of response to immunomodulatory drugs and may also be classified according to whether they are cell-specific or tumor-tissue-specific. Cell-specific markers are evaluated under the microscope as (I) morphological, corresponding to the assessment of tumor infiltrating immune cells on routine hematoxylin & eosin (H&E) sections; and (II) immunophenotypic, including the immunohistochemical (IHC) assessment of markers characteristic for tumor infiltrating immune cells. Tumor-tissue-specific markers are assessed in tissue extracts that may be enriched in neoplastic cells but almost inevitably also contain stromal and immune cells infiltrating the tumor. Such markers include (I) immune-response-related gene expression profiles, and (II) tumor genotype characteristics, as recently assessed with large-scale genotyping methods, usually next generation sequencing (NGS) applications. Herein, we discuss the biological nature of immunodiagnostic markers, their potential clinical relevance and the shortcomings that have, as yet, prevented their clinical application. PMID:27563650

  15. Towards tumor immunodiagnostics.

    PubMed

    Kourea, Helen; Kotoula, Vassiliki

    2016-07-01

    Immunodiagnostic markers applicable on tissue or cytologic material may be prognostic or predictive of response to immunomodulatory drugs and may also be classified according to whether they are cell-specific or tumor-tissue-specific. Cell-specific markers are evaluated under the microscope as (I) morphological, corresponding to the assessment of tumor infiltrating immune cells on routine hematoxylin & eosin (H&E) sections; and (II) immunophenotypic, including the immunohistochemical (IHC) assessment of markers characteristic for tumor infiltrating immune cells. Tumor-tissue-specific markers are assessed in tissue extracts that may be enriched in neoplastic cells but almost inevitably also contain stromal and immune cells infiltrating the tumor. Such markers include (I) immune-response-related gene expression profiles, and (II) tumor genotype characteristics, as recently assessed with large-scale genotyping methods, usually next generation sequencing (NGS) applications. Herein, we discuss the biological nature of immunodiagnostic markers, their potential clinical relevance and the shortcomings that have, as yet, prevented their clinical application. PMID:27563650

  16. Accessory parotid gland tumors

    PubMed Central

    Ramachar, Sreevathsa M.; Huliyappa, Harsha A.

    2012-01-01

    Tumors of accessory parotid gland are considered in the differential diagnosis of a mid cheek mass. Parotidectomy is the procedure of choice. All pathological types of parotid main gland tumors occur in the accessory parotid gland also. Presenting as a mid cheek or infrazygomatic mass, the tumors of this accessory parotid gland are notorious for recurrences, if adequate margins are not achieved. We describe two such cases of such a tumor. 40-year-old male with a slowly progressive mid cheek mass was operated by a mid cheek incision. Histopathology of the tumor was pleomorphic adenoma. Facial nerve paresis recovered complelety in 6 months. A 52-year-old female with progressive mid cheek mass who underwent parotidectomy and neck dissection by a modified Blair's incision was diagnosed with extranodal marginal zone lymphoma with focal transformation to a diffuse large B-cell lymphoma. Chemotherapy with CHOP regime was initiated. There was no recurrence at 6 months of follow-up. Lymphoma of accessory parotid gland is a very rare tumor. Standard parotidectomy incision is advocated to prevent damage to facial nerve branches. PMID:23483721

  17. [Endosonography of stomach tumors].

    PubMed

    Nattermann, C; Dancygier, H

    1992-11-01

    Based on own experience and on the published literature we report about indications and efficiency of endosonography (EUS) in gastric tumors. The following conclusions can be drawn at the present time. Submucous tumors can be clearly differentiated from extragastric compressions. Although the endosonographic aspect does not allow to formulate an etiologic diagnosis, EUS findings can give hints regarding the nature of the submucous tumor (e.g. leiomyoma, lipoma, cyst). In 75% of cases malignant submucous tumors can be visualized and a correct preoperative staging can be performed. EUS is of special importance in the description of gastric carcinoma. The pT stage can be correctly determined preoperatively in about 80% (69-92%) of cases. Accompanying inflammation in early gastric cancer can lead to overstaging. The sensitivity for local lymph node metastases reaches about 77% (50-88%). Gastric non-Hodgkin lymphomas can be excellently visualized with EUS. The sensitivity amounts to 90-100% and in about 90% of cases the extent of the tumor can be correctly determined preoperatively. The response to radio-chemotherapy of gastric non-Hodgkin lymphomas can be monitored easily with the method. At the present time EUS is the most sensitive imaging tool in visualizing and staging of gastric tumors. Its main advantage is the exact demonstration of intramural and paragastric alterations. However, despite the use of high ultrasonic frequencies and the excellent demonstration of even tiny details with EUS, biopsies for histologic evaluation are still mandatory, especially when dealing with gastric ulcer.

  18. [Grading of neuroendocrine tumors].

    PubMed

    Saeger, W; Schnabel, P A; Komminoth, P

    2016-07-01

    The current WHO classification of neuroendocrine tumors (NET) differentiates between typical carcinoids (low grade NET), atypical carcinoids (intermediate grade NET) and small cell and large cell carcinomas (high grade NET) according to the prognosis. Neuroendocrine neoplasms (NEN) of the gastrointestinal tract and the pancreas are graded in an identical way. Together with the TNM system this enables a preoperative estimation of the prognosis in biopsies and fine needle aspirates. Well-differentiated tumors are graded into G1 tumors by the number of mitoses, <2 per 10 high-power fields (HPF) and the Ki-67 (index <3 %) and G2 tumors (2-20 mitoses/10 HPF, Ki-67 3-20 %). Discrepancies between the number of mitoses and the Ki-67 index are not uncommon and in these cases the higher value of the two should be applied. The more differentiated tumors of the G3 type have to be differentiated from undifferentiated carcinomas of the small cell type and large cell type with a much poorer prognosis. Prognosis relevant grading of thyroid cancers is achieved by special subtyping so that the G1-G3 system is not applicable. The rare cancers of the parathyroid gland and of the pituitary gland are not graded. Adrenal tumors also have no grading system. The prognosis is dependent on the Ki-67 index and with some reservations on the established scoring systems. PMID:27379621

  19. Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes

    NASA Astrophysics Data System (ADS)

    Liu, Chunyan; Qi, Yifei; Qiao, Ruirui; Hou, Yi; Chan, Kaying; Li, Ziqian; Huang, Jiayi; Jing, Lihong; Du, Jun; Gao, Mingyuan

    2016-06-01

    Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual

  20. Preparation and quality test of superparamagnetic iron oxide labeled antisense oligodeoxynucleotide probe: a preliminary study.

    PubMed

    Wen, Ming; Li, Bibo; Ouyang, Yu; Luo, Yi; Li, Shaolin

    2009-06-01

    Molecular imaging of tumor antisense gene techniques have been applied to the study of magnetic resonance (MR) gene imaging associated with malignant tumors. In this study, we designed, synthesized, and tested a novel molecular probe, in which the antisense oligodeoxynucleotide (ASODN) was labeled with superparamagnetic iron oxide (SPIO), and its efficiency was examined by in vitro MR imaging after SK-Br-3 mammary carcinoma cell lines (oncocytes) transfection. The SPIO-labeled ASODN probe was prepared through SPIO conjugated to ASODN using a chemical cross linking method. Its morphology and size were detected by atomic force microscope, size distribution were detected by laser granulometer, the conjugating rate and biological activity were determined by high performance liquid chromatography, and the stability was determined by polyacrylamide gel electrophoresis. After that, the probes were transfected into the SK-Br-3 oncocytes, cellular iron uptake was analyzed qualitatively at light and electron microscopy and was quantified at atomic absorption spectrometry, and the signal change of the transfected cells was observed and measured using MR imaging. The morphology of the SPIO-labeled ASODN probe was mostly spherical with well-distributed scattering, and the diameters were between 25 and 40 nm (95%) by atomic force microscope and laser granulometer, the conjugating rate of the probe was 99%. Moreover, this probe kept its activity under physiological conditions and could conjugate with antisense oligodeoxynucleotide. In addition, light microscopy revealed an intracellular uptake of iron oxides in the cytosol and electron microscopic studies revealed a lysosomal deposition of iron oxides in the transfected SK-Br-3 oncocytes by antisense probes, some of them gathered stacks, and the iron content of the group of transfected SK-Br-3 oncocytes by antisense probe is significantly higher (18.37 +/- 0.42 pg) than other contrast groups, the MR imaging showed that

  1. [Enophthalmos in an orbital tumor].

    PubMed

    Szabo, Bianca; Szabo, I; Nicula, Cristina; Popescu, Livia Adriana

    2013-01-01

    Enophtalmus is an unusual sign of the orbital tumors often represented by proptosis. One patient with enophtalmus and intraorbital tumor and aplasy is presented. The treatment of choice of orbital tumor is complete surgical excision and careful follow-up. Considering the more aggressive course followed by recurrent tumor, correct diagnosis and management is essential.

  2. Hand-held survey probe

    DOEpatents

    Young, Kevin L [Idaho Falls, ID; Hungate, Kevin E [Idaho Falls, ID

    2010-02-23

    A system for providing operational feedback to a user of a detection probe may include an optical sensor to generate data corresponding to a position of the detection probe with respect to a surface; a microprocessor to receive the data; a software medium having code to process the data with the microprocessor and pre-programmed parameters, and making a comparison of the data to the parameters; and an indicator device to indicate results of the comparison. A method of providing operational feedback to a user of a detection probe may include generating output data with an optical sensor corresponding to the relative position with respect to a surface; processing the output data, including comparing the output data to pre-programmed parameters; and indicating results of the comparison.

  3. Methods of staining target chromosomal DNA employing high complexity nucleic acid probes

    DOEpatents

    Gray, Joe W.; Pinkel, Daniel; Kallioniemi, Ol'li-Pekka; Kallioniemi, Anne; Sakamoto, Masaru

    2006-10-03

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML), retinoblastoma, ovarian and uterine cancers, and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

  4. Assessment of breast tumor size in electrical impedance scanning

    NASA Astrophysics Data System (ADS)

    Kim, Sungwhan

    2012-02-01

    Electrical impedance scanning (EIS) is a newly introduced imaging technique for early breast cancer detection. In EIS, we apply a sinusoidal voltage between a hand-held electrode and a scanning probe placed on the breast skin to make current travel through the breast. We measure induced currents (Neumann data) through the scanning probe. In this paper, we investigate the frequency-dependent behavior of the induced complex potential and show how the frequency differential of the current measurement on the scanning probe reflects the contrast in complex conductivity values between surrounding and cancerous tissues. Furthermore, we develop the formula for breast tumor size using the frequency differential of the current measurement and provide its feasibility.

  5. Brain tumors in infants

    PubMed Central

    Ghodsi, Seyyed Mohammad; Habibi, Zohreh; Hanaei, Sara; Moradi, Ehsan; Nejat, Farideh

    2015-01-01

    Background: Brain tumors in infants have different clinical presentations, anatomical distribution, histopathological diagnosis, and clinical prognosis compared with older children. Materials and Methods: A retrospective analysis was done in patients <12 months old who were operated on for primary brain tumor in Children's Hospital Medical Center since 2008 to 2014. Results: Thirty-one infants, 20 males and 11 females, with the mean age of 7.13 months (0.5–12) were enrolled. There were 16 supratentorial and 15 infratentorial tumors. The presenting symptoms included increased head circumference (16); bulge fontanel (15); vomiting (15); developmental regression (11); sunset eye (7); seizure (4); loss of consciousness (4); irritability (3); nystagmus (2); visual loss (2); hemiparesis (2); torticollis (2); VI palsy (3); VII, IX, X nerve palsy (each 2); and ptosis (1). Gross total and subtotal resection were performed in 19 and 11 cases, respectively. Fourteen patients needed external ventricular drainage in the perioperative period, from whom four infants required a ventriculoperitoneal shunt. One patient underwent ventriculoperitoneal shunting without tumor resection. The most common histological diagnoses were primitive neuroectodermal tumor (7), followed by anaplastic ependymoma (6) and grade II ependymoma. The rate of 30-day mortality was 19.3%. Eighteen patients are now well-controlled with or without adjuvant therapy (overall survival; 58%), from whom 13 cases are tumor free (disease free survival; 41.9%), 3 cases have residual masses with fixed or decreased size (progression-free survival; 9.6%), and 2 cases are still on chemotherapy. Conclusion: Brain tumors in infants should be treated with surgical resection, followed by chemotherapy when necessary. PMID:26962338

  6. Neurologic complications of cardiac tumors.

    PubMed

    Roeltgen, David; Kidwell, Chelsea S

    2014-01-01

    Cardiac tumors are an uncommon cause for neurologic disease, but if undiagnosed can be associated with devastating neurologic consequences. Primary cardiac tumors, both benign and neoplastic, and metastatic tumors occur. Primary cardiac tumors are more likely to be associated with neurologic embolic complications. Metastatic cardiac tumors are more likely to be associated with valvular distraction, arrhythmia, diminished cardiac output and indirect neurological dysfunction. Primary and metastatic cardiac tumors may result in cerebral metastatic disease. Atrial myxoma, a benign primary cardiac tumor, is the most common cardiac tumor associated with neurologic disease, and most commonly causes cerebral embolization and stroke. The use of thrombolytic therapy for these strokes is controversial. Additionally, delayed manifestations, including aneurysm formation and intracranial hemorrhage, are possible. Aneurysm formation has been described as occurring after removal of the primary tumor. The availability of noninvasive cardiac imaging has significantly helped decrease the neurologic morbidity of cardiac tumors and has led to frequent successful intervention. PMID:24365298

  7. Quantum Dots as Cellular Probes

    SciTech Connect

    Alivisatos, A. Paul; Gu, Weiwei; Larabell, Carolyn

    2004-09-16

    Robust and bright light emitters, semiconductor nanocrystals[quantum dots (QDs)] have been adopted as a new class of fluorescent labels. Six years after the first experiments of their uses in biological applications, there have been dramatic improvements in understanding surface chemistry, biocompatibility, and targeting specificity. Many studies have shown the great potential of using quantum dots as new probes in vitro and in vivo. This review summarizes the recent advances of quantum dot usage at the cellular level, including immunolabeling, cell tracking, in situ hybridization, FRET, in vivo imaging, and other related technologies. Limitations and potential future uses of quantum dot probes are also discussed.

  8. Probe Project Status and Accomplishments

    SciTech Connect

    Burris, RD

    2001-05-07

    The Probe project has completed its first full year of operation. In this document we will describe the status of the project as of December 31, 2000. We will describe the equipment configuration, then give brief descriptions of the various projects undertaken to date. We will mention first those projects performed for outside entities and then those performed for the benefit of one of the Probe sites. We will then describe projects that are under consideration, including some for which initial actions have been taken and others which are somewhat longer-term.

  9. Chemoimmunotherapy: reengineering tumor immunity.

    PubMed

    Chen, Gang; Emens, Leisha A

    2013-02-01

    Cancer chemotherapy drugs have long been considered immune suppressive. However, more recent data indicate that some cytotoxic drugs effectively treat cancer in part by facilitating an immune response to the tumor when given at the standard dose and schedule. These drugs induce a form of tumor cell death that is immunologically active, thereby inducing an adaptive immune response specific for the tumor. In addition, cancer chemotherapy drugs can promote tumor immunity through ancillary and largely unappreciated immunologic effects on both the malignant and normal host cells present within the tumor microenvironment. These more subtle immunomodulatory effects are dependent on the drug itself, its dose, and its schedule in relation to an immune-based intervention. The recent approvals of two new immune-based therapies for prostate cancer and melanoma herald a new era in cancer treatment and have led to heightened interest in immunotherapy as a valid approach to cancer treatment. A detailed understanding of the cellular and molecular basis of interactions between chemotherapy drugs and the immune system is essential for devising the optimal strategy for integrating new immune-based therapies into the standard of care for various cancers, resulting in the greatest long-term clinical benefit for cancer patients. PMID:23389507

  10. Neuroimaging of spine tumors.

    PubMed

    Pinter, Nandor K; Pfiffner, Thomas J; Mechtler, Laszlo L

    2016-01-01

    Intramedullary, intradural/extramedullary, and extradural spine tumors comprise a wide range of neoplasms with an even wider range of clinical symptoms and prognostic features. Magnetic resonance imaging (MRI), commonly used to evaluate the spine in patients presenting with pain, can further characterize lesions that may be encountered on other imaging studies, such as bone scintigraphy or computed tomography (CT). The advantage of the MRI is its multiplane capabilities, superior contrast agent resolution, and flexible protocols that play an important role in assessing tumor location, extent in directing biopsy, in planning proper therapy, and in evaluating therapeutic results. A multimodality approach can be used to fully characterize the lesion and the combination of information obtained from the different modalities usually narrows the diagnostic possibilities significantly. The diagnosis of spinal tumors is based on patient age, topographic features of the tumor, and lesion pattern, as seen at CT and MRI. The shift to high-end imaging incorporating diffusion-weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy, whole-body short tau inversion recovery, positron emission tomography, intraoperative and high-field MRI as part of the mainstream clinical imaging protocol has provided neurologists, neuro-oncologists, and neurosurgeons a window of opportunity to assess the biologic behavior of spine neoplasms. This chapter reviews neuroimaging of spine tumors, primary and secondary, discussing routine and newer modalities that can reduce the significant morbidity associated with these neoplasms. PMID:27430436

  11. Intraoperative Targeted Optical Imaging: A Guide towards Tumor-Free Margins in Cancer Surgery

    PubMed Central

    Orbay, Hakan; Bean, Jero; Zhang, Yin; Cai, Weibo

    2014-01-01

    Over the last several decades, development of various imaging techniques such as computed tomography, magnetic resonance imaging, and positron emission tomography greatly facilitated the early detection of cancer. Another important aspect that is closely related to the survival of cancer patients is complete tumor removal during surgical resection. The major obstacle in achieving this goal is to distinguish between tumor tissue and normal tissue during surgery. Currently, tumor margins are typically assessed by visual assessment and palpation of the tumor intraoperatively. However, the possibility of microinvasion to the surrounding tissues makes it difficult to determine an adequate tumor-free excision margin, often forcing the surgeons to perform wide excisions including the healthy tissue that may contain vital structures. It would be ideal to remove the tumor completely, with minimal safety margins, if surgeons could see precise tumor margins during the operation. Molecular imaging with optical techniques can visualize the tumors via fluorophore conjugated probes targeting tumor markers such as proteins and enzymes that are upregulated during malignant transformation. Intraoperative use of this technique may facilitate complete excision of the tumor and tumor micromasses located beyond the visual capacity of the naked eye, ultimately improving the clinical outcome and survival rates of cancer patients. PMID:24372232

  12. Infrequent genomic rearrangement and normal expression of the putative RB1 gene in retinoblastoma tumors

    SciTech Connect

    Goddard, A.D.; Balakier, H.; Canton, M.; Dunn, J.; Squire, J.; Reyes, E.; Becker, A.; Phillips, R.A.; Gallie, B.L.

    1988-05-01

    Retinoblastoma (RB) tumors develop when both alleles of a gene (RB1) are mutated and unable to function normally. Recently, others reported the cloning of a gene, 4.7R, with some properties expected for the RB1 gene, namely, a high frequency (30%) of genomic rearrangements in tumors and absence of message in all RB tumors examined. To extend the characterization of this gene, the authors used 4.7R probes to search for genomic rearrangements of DNA and to study the expression of the 4.7R gene in RB tumors, osteosarcoma (OS) tumors arising in RB patients, and other normal and malignant tissues. In 34 previously unreported RB and OS tumors arising in RB patients, the authors observed only four (12%) with genomic abnormalities. Transcripts of 4.7R were present in 12 of 17 RB tumors, 2 of 2 OS tumors, and all non-RB tumors and normal tissues tested. They were unable to confirm the high frequency of truncated messages of 4.7R in RB tumors reported by others, but did not confirm the presence of a truncated transcription in the RB cell line Y79. Of the RB and RB-related OS tumors which appeared normal on Southern blots, 2 of 16 or 12% had abnormal transcripts, giving a combined frequency of 22% abnormalities in the 4.7R gene detectable by Southern and Northern (RNA) blot analyses.

  13. EPR oximetry of tumors in vivo in cancer therapy

    NASA Astrophysics Data System (ADS)

    Šentjurc, Marjeta; Čemažar, Maja; Serša, Gregor

    2004-05-01

    The partial oxygen pressure ( pO 2) in tumors is considered to be one of important factors that affect the response of tumors to different treatment. Therefore, we anticipate that the information about the variation of oxygen concentration in tumors can be used as a guide for individualizing radiotherapy, chemotherapy, and especially the combined therapies. There is thus a need to obtain quantitative data on the effects of different therapies on tumor oxygenation under in vivo conditions. One of the methods, which enable these measurements is EPR oximetry. In this work basic principles of the method will be described as well as some examples of tumor oxygenation changes after application of chemotherapeutic drugs (vinblastine, cisplatin, bleomycin) or electric pulses in combination with cisplatin or bleomycin to fibrosarcoma SA-1 tumors in mice. A paramagnetic probe, a char of Bubinga tree, was implanted into the tumor (center and periphery) and in the muscle or subcutis. EPR spectra line-width, which is proportional to oxygen concentration, was measured with time after the treatments. Tumor oxygenation was reduced for 58% of pretreatment value 1 h after intraperitoneal injection of 2.5 mg kg -1 VLB and returned to pretreatment level within 24 h. Reduction in oxygenation of muscle and subcutis was much smaller and returned to pretreatment value faster as in tumors. With cisplatin (4 mg kg -1) and bleomicyn (1 mg kg -1) the reduction was less than 15%, but increases in combined therapy to 70%. Similar reduction was observed also with electric pulses alone (eight pulses, 1300 V cm -1, 100 μs, 1 Hz) with fast recovery of 8 h. After electrochemotherapy the recovery was slower and occurs only after 48 h. This study demonstrates that EPR oximetry is a sensitive method for monitoring changes in tissue oxygenation after different treatments, which may have implications in controlling side effects of therapy and in the planning of combined treatments.

  14. [Hepatic tumors and radiotherapy].

    PubMed

    Rio, E; Mornex, F; Peiffert, D; Huertas, A

    2016-09-01

    Recent technological developments led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumors as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. For hepatocellular carcinoma 5 to 10cm (or more), a conformational radiation with or without intensity modulation is performed. Stereotactic body radiotherapy (SBRT) is being evaluated and is increasingly proposed as an alternative to radiofrequency ablative treatment for primary or secondary tumors (typically less than 5cm). Tumor (and liver) movements induced by respiratory motions must be taken into account. Strict dosimetric criteria must be met with particular attention to the dose-volume histograms to liver and the hollow organs, including cases of SBRT. PMID:27521035

  15. Subcutaneous solitary fibrous tumor.

    PubMed

    Yoshida, Yuichi; Kubota, Yumiko; Yamaguchi, Takahiro; Iwasaki, Hiroshi; Nakayama, Juichiro

    2004-12-01

    We describe a unique case of subcutaneous solitary fibrous tumor (SFT) in a 56-year-old female patient. The patient had been aware of a painless soft mass in her back for ten years. The lesion was surgically excised. Histological examination revealed that the well-defined mass was composed of a proliferation of spindle-shaped fibroblastic cells and polygonal cells embedded in a fibrous matrix corresponding to the so-called "patternless pattern". A prominent pericytomatous pattern (hemangiopericytoma-like structures), focal myxoid changes, and thick hyalinized collagen fibers were also observed. Immunohistochemical stainings for CD34 and bcl-2 were positive in the tumor cells. These features are compatible with SFT. We suggest that SFT should be included in the differential diagnosis of subcutaneous spindle cell tumors.

  16. Decay Dynamics of Tumors

    PubMed Central

    2016-01-01

    The fractional cell kill is a mathematical expression describing the rate at which a certain population of cells is reduced to a fraction of itself. We investigate the mathematical function that governs the rate at which a solid tumor is lysed by a cell population of cytotoxic lymphocytes. We do it in the context of enzyme kinetics, using geometrical and analytical arguments. We derive the equations governing the decay of a tumor in the limit in which it is plainly surrounded by immune cells. A cellular automaton is used to test such decay, confirming its validity. Finally, we introduce a modification in the fractional cell kill so that the expected dynamics is attained in the mentioned limit. We also discuss the potential of this new function for non-solid and solid tumors which are infiltrated with lymphocytes. PMID:27310010

  17. [Familial pituitary tumors].

    PubMed

    Yoshimoto, K; Saito, S

    1995-11-01

    Familial pituitary tumors are relatively rare. Most commonly, they occur as a part of multiple endocrine neoplasia type 1 (MEN 1). However, familial pituitary adenomas unrelated MEN 1 (familial pituitary adenomas) are extremely rare. In review of MEN 1 in Japan, 60% of the patients with MEN 1 had pituitary tumors. Only 45 cases of familial pituitary adenomas have been reported from 20 families. In our review of familial pituitary adenomas, 30 (67%) of 45 reported cases are acromegaly or gigantism. This incidence is much higher than 28% in MEN 1 patients with pituitary tumors. Allelic deletions at 11q13 were identified in MEN 1 associated pituitary adenomas and familial pituitary adenomas in two gigantism brothers. PMID:8538028

  18. Gastrointestinal stromal tumor

    PubMed Central

    Yue, Changjun

    2012-01-01

    Gastrointestinal stromal tumor has received a lot of attention over the last 10 years due to its unique biologic behavior, clinicopathological features, molecular mechanisms, and treatment implications. GIST is the most common mesenchymal neoplasm in the gastrointestinal tract and has emerged from a poorly understood and treatment resistant neoplasm to a well-defined tumor entity since the discovery of particular molecular abnormalities, KIT and PDGFRA gene mutations. The understanding of GIST biology at the molecular level promised the development of novel treatment modalities. Diagnosis of GIST depends on the integrity of histology, immunohistochemistry and molecular analysis. The risk assessment of the tumor behavior relies heavily on pathological evaluation and significantly impacts clinical management. In this review, historic review, epidemiology, pathogenesis and genetics, diagnosis, role of molecular analysis, prognostic factor and treatment strategies have been discussed. PMID:22943011

  19. A fluorescent probe for ecstasy.

    PubMed

    Masseroni, D; Biavardi, E; Genovese, D; Rampazzo, E; Prodi, L; Dalcanale, E

    2015-08-18

    A nanostructure formed by the insertion in silica nanoparticles of a pyrene-derivatized cavitand, which is able to specifically recognize ecstasy in water, is presented. The absence of effects from interferents and an efficient electron transfer process occurring after complexation of ecstasy, makes this system an efficient fluorescent probe for this popular drug.

  20. Samara Probe For Remote Imaging

    NASA Technical Reports Server (NTRS)

    Burke, James D.

    1989-01-01

    Imaging probe descends through atmosphere of planet, obtaining images of ground surface as it travels. Released from aircraft over Earth or from spacecraft over another planet. Body and single wing shaped like samara - winged seed like those of maple trees. Rotates as descends, providing panoramic view of terrain below. Radio image obtained by video camera to aircraft or spacecraft overhead.

  1. SUB-SLAB PROBE INSTALLATION

    EPA Science Inventory

    Sub-slab sampling has become an integral part of vapor intrusion investigations. It is now recommended in guidance documents developed by EPA and most states. A method for sub-slab probe installation was devised in 2002, presented at conferences through 2005, and finally docume...

  2. Health. CEM Probe, January 1977.

    ERIC Educational Resources Information Center

    Billington, Roy

    The importance of health and its relationship to personal and community life are explored in this issue of PROBE. Designed to acquaint British secondary school youth with topical problems, the series contains discussion and case studies of national and world issues, followed by questions for student discussion and research. Nine chapters comprise…

  3. Galileo Space Probe News Conference

    NASA Astrophysics Data System (ADS)

    1996-01-01

    This NASA Kennedy Space Center (KSC) video release presents Part 3 of a press conference from Ames Research Center (ARC) regarding the successful entry of the Galileo Space Probe into Jupiter's atmosphere. The press conference panel is comprised of twelve principal investigators and project scientists that oversee the Galileo mission. The press conference question and answer period is continued from Part 2. Atmospheric thermal structure, water abundances, wind profiles, radiation, cloud structure, chemical composition, and electricity are among the topics discussed. The question and answer period is followed by a presentation in which all of the visuals that are shown during the press conference are reviewed. The video ends with several animations depicting the entry of the probe, descent, and the first measurements of the Jovian atmosphere, historical footage of the building of the probe, and a short interview with Dr. Richard Young (Galileo Probe Scientist, ARC). Parts 1 and 2 of the press conference can be found in document numbers NONP-NASA-VT-2000001073, and NONP-NASA-VT-2000001074.

  4. OCR Pace on Probes Quickens

    ERIC Educational Resources Information Center

    Maxwell, Lesli A.

    2011-01-01

    In the 21 months since U.S. Secretary of Education Arne Duncan stood on an iconic bridge in Selma, Alabama, and pledged to aggressively combat discrimination in the nation's schools, federal education officials have launched dozens of new probes in school districts and states that reach into civil rights issues that previously received little, if…

  5. Detection Limits of Intraoperative Near Infrared Imaging for Tumor Resection

    PubMed Central

    THURBER, GREG M.; FIGUEIREDO, JOSE-LUIZ; WEISSLEDER, RALPH

    2013-01-01

    Background and Objectives The application of fluorescent molecular imaging to surgical oncology is a developing field with the potential to reduce morbidity and mortality. However, the detection thresholds and other requirements for successful intervention remain poorly understood. Here we modeled and experimentally validated depth and size of detection of tumor deposits, trade-offs in coverage and resolution of areas of interest, and required pharmacokinetics of probes based on differing levels of tumor target presentation. Methods Three orthotopic tumor models were imaged by widefield epifluorescence and confocal microscopes, and the experimental results were compared with pharmacokinetic models and light scattering simulations to determine detection thresholds. Results Widefield epifluorescence imaging can provide sufficient contrast to visualize tumor margins and detect tumor deposits 3–5 mm deep based on labeled monoclonal antibodies at low objective magnification. At higher magnification, surface tumor deposits at cellular resolution are detectable at TBR ratios achieved with highly expressed antigens. Conclusions A widefield illumination system with the capability for macroscopic surveying and microscopic imaging provides the greatest utility for varying surgical goals. These results have implications for system and agent designs, which ultimately should aid complete resection in most surgical beds and provide real-time feedback to obtain clean margins. PMID:20872807

  6. MR Molecular Imaging of Tumor Vasculature and Vascular Targets

    PubMed Central

    Pathak, Arvind P.; Penet, Marie-France; Bhujwalla, Zaver M.

    2016-01-01

    Tumor angiogenesis and the ability of cancer cells to induce neovasculature continue to be a fascinating area of research. As the delivery network that provides substrates and nutrients, as well as chemotherapeutic agents to cancer cells, but allows cancer cells to disseminate, the tumor vasculature is richly primed with targets and mechanisms that can be exploited for cancer cure or control. The spatial and temporal heterogeneity of tumor vasculature, and the heterogeneity of response to targeting, make noninvasive imaging essential for understanding the mechanisms of tumor angiogenesis, tracking vascular targeting, and detecting the efficacy of antiangiogenic therapies. With its noninvasive characteristics, exquisite spatial resolution and range of applications, magnetic resonance imaging (MRI) techniques have provided a wealth of functional and molecular information on tumor vasculature in applications spanning from “bench to bedside”. The integration of molecular biology and chemistry to design novel imaging probes ensures the continued evolution of the molecular capabilities of MRI. In this review, we have focused on developments in the characterization of tumor vasculature with functional and molecular MRI. PMID:20807600

  7. Validation of DNA probes for molecular cytogenetics by mapping onto immobilized circular DNA

    SciTech Connect

    Greulich-Bode, Karin; Wang, Mei; Rhein, Andreas; Weier, Jingly; Weier, Heinz-Ulli

    2008-12-16

    Fluorescence in situ hybridization (FISH) is a sensitive and rapid procedure to detect gene rearrangements in tumor cells using non-isotopically labeled DNA probes. Large insert recombinant DNA clones such as bacterial artificial chromosome (BAC) or P1/PAC clones have established themselves in recent years as preferred starting material for probe preparations due to their low rates of chimerism and ease of use. However, when developing probes for the quantitative analysis of rearrangements involving genomic intervals of less than 100kb, careful probe selection and characterization are of paramount importance. We describe a sensitive approach to quality control probe clones suspected of carrying deletions or for measuring clone overlap with near kilobase resolution. The method takes advantage of the fact that P1/PAC/BAC's can be isolated as circular DNA molecules, stretched out on glass slides and fine-mapped by multicolor hybridization with smaller probe molecules. Two examples demonstrate the application of this technique: mapping of a gene-specific {approx}6kb plasmid onto an unusually small, {approx}55kb circular P1 molecule and the determination of the extent of overlap between P1 molecules homologous to the human NF-?B2 locus. The relatively simple method presented here does not require specialized equipment and may thus find widespread applications in DNA probe preparation and characterization, the assembly of physical maps for model organisms or in studies on gene rearrangements.

  8. Validation of DNA probes for molecular cytogenetics by mapping onto immobilized circular DNA

    SciTech Connect

    Greulich-Bode, Karin M.; Wang, Mei; Rhein, Andreas P.; Weier, Jingly F.; Weier, Heinz-Ulli G.

    2008-12-04

    Fluorescence in situ hybridization (FISH) is a sensitive and rapid procedure to detect gene rearrangements in tumor cells using non-isotopically labeled DNA probes. Large insert recombinant DNA clones such as bacterial artificial chromosome (BAC) or P1/PAC clones have established themselves in recent years as preferred starting material for probe preparations due to their low rates of chimerism and ease of use. However, when developing probes for the quantitative analysis of rearrangements involving genomic intervals of less than 100kb, careful probe selection and characterization are of paramount importance. We describe a sensitive approach to quality control probe clones suspected of carrying deletions or for measuring clone overlap with near kilobase resolution. The method takes advantage of the fact that P1/PAC/BAC's can be isolated as circular DNA molecules, stretched out on glass slides and fine-mapped by multicolor hybridization with smaller probe molecules. Two examples demonstrate the application of this technique: mapping of a gene-specific {approx}6kb plasmid onto an unusually small, {approx}55kb circular P1 molecule and the determination of the extent of overlap between P1 molecules homologous to the human NF-{kappa}B2 locus. The relatively simple method presented here does not require specialized equipment and may thus find widespread applications in DNA probe preparation and characterization, the assembly of physical maps for model organisms or in studies on gene rearrangements.

  9. Calcifying Fibrous Tumor

    PubMed Central

    Chorti, Angeliki; Papavramidis, Theodossis S.; Michalopoulos, Antonios

    2016-01-01

    Abstract Calcifying fibrous tumor (CFT) is a benign lesion characterized by its specific histological findings and is found as solitary or multiple lesions in several locations of the human body. The aim of the present systematic review is to give a detailed account of all reported cases of CFT in the literature and to analyze the available data, to completely characterize the entity from epidemiological, medical, and surgical aspects. A bibliographic research was performed from 1988 until 2015. A database with the patients’ characteristics was made, including sex, age, location of the tumor, symptoms, symptoms duration, size of the tumor, diagnostic methods, treatment, metastasis, and follow-up. A total of 104 articles were identified, reporting 157 cases of CFT. Mean age of patients was 33.58 years and the ratio between men and women was 1:1.27. The most common locations of CFT were stomach (18%), small intestine (8.7%), pleura (9.9%), mesentery (5%), and peritoneum (6.8%). Mean diameter of the tumor was estimated 4.6 cm. The correlations proceeded showed that as age increases, size decreases (P = 0.001) and that the tumor is larger in females (P = 0.027). Kruskal-Wallis test showed that the larger tumors appear in the neck and adrenal gland (P = 0.001). The percentage of asymptomatic patients was 30.57%. Computed tomography and biopsy were the most common tests for the diagnosis of CFT. Open surgical procedure was performed in the majority of cases. The median hospitalization was 6.06 days and the mean follow-up period was 29.97 months. Recurrences were mentioned in 10 of 96 patients with available data. No deaths owing to CFT were mentioned in the literature. CFT should be included in the differential diagnosis of enlarging mass revealed by clinical or imaging examination either incidentally or after specific acute or chronic symptomatology. PMID:27196478

  10. Genetic imbalances detected by multiplex ligation-dependent probe amplification in a cohort of patients with oral squamous cell carcinoma-the first step towards clinical personalized medicine.

    PubMed

    Ribeiro, Ilda Patrícia; Marques, Francisco; Caramelo, Francisco; Ferrão, José; Prazeres, Hugo; Julião, Maria José; Rifi, Widad; Savola, Suvi; de Melo, Joana Barbosa; Baptista, Isabel Poiares; Carreira, Isabel Marques

    2014-05-01

    Oral tumors are a growing health problem worldwide; thus, it is mandatory to establish genetic markers in order to improve diagnosis and early detection of tumors, control relapses and, ultimately, delineate individualized therapies. This study was the first to evaluate and discuss the clinical applicability of a multiplex ligation-dependent probe amplification (MLPA) probe panel directed to head and neck cancer. Thirty primary oral squamous cell tumors were analyzed using the P428 MLPA probe panel. We detected genetic imbalances in 26 patients and observed a consistent pattern of distribution of genetic alterations in terms of losses and gains for some chromosomes, particularly for chromosomes 3, 8, and 11. Regarding the latter, some specific genes were highlighted due to frequent losses of genetic material--RARB, FHIT, CSMD1, GATA4, and MTUS1--and others due to gains--MCCC1, MYC, WISP1, PTK2, CCND1, FGF4, FADD, and CTTN. We also verified that the gains of MYC and WISP1 genes seem to suggest higher propensity of tumors localized in the floor of the mouth. This study proved the value of this MLPA probe panel for a first-tier analysis of oral tumors. The probemix was developed to include target regions that have been already shown to be of diagnostic/prognostic relevance for oral tumors. Furthermore, this study emphasized several of those specific genetic targets, suggesting its importance to oral tumor development, to predict patients' outcomes, and also to guide the development of novel molecular therapies.

  11. Nucleic acid probes in diagnostic medicine

    NASA Technical Reports Server (NTRS)

    Oberry, Phillip A.

    1991-01-01

    The need for improved diagnostic procedures is outlined and variations in probe technology are briefly reviewed. A discussion of the application of probe technology to the diagnosis of disease in animals and humans is presented. A comparison of probe versus nonprobe diagnostics and isotopic versus nonisotopic probes is made and the current state of sequence amplification is described. The current market status of nucleic acid probes is reviewed with respect to their diagnostic application in human and veterinary medicine. Representative product examples are described and information on probes being developed that offer promise as future products is discussed.

  12. Intramasseteric solitary fibrous tumor.

    PubMed

    Dogan, Ersoy; Erdag, Taner Kemal; Ikiz, Ahmet Omer; Guneri, Ataman; Sarioglu, Sulen

    2013-03-01

    Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm that usually arises from the pleura. SFTs occurring within the head and neck region are uncommon. Recently, it has been described in various head and neck sites such as oral cavity, nasal cavity, paranasal sinuses, salivary glands, thyroid, buccal space, and larynx. Here, we report a case of SFT originating in the masseter muscle of a 27-year-old woman. To our knowledge, this is the first description of a SFT of the head and neck region, arising within the masseter muscle. We present the clinical history, radiologic and histopathologic findings as well as immunoreactivity of this tumor.

  13. High pressure optical combustion probe

    SciTech Connect

    Woodruff, S.D.; Richards, G.A.

    1995-06-01

    The Department of Energy`s Morgantown Energy Technology Center has developed a combustion probe for monitoring flame presence and heat release. The technology involved is a compact optical detector of the OH radical`s UV fluorescence. The OH Monitor/Probe is designed to determine the flame presence and provide a qualitative signal proportional to the flame intensity. The probe can be adjusted to monitor a specific volume in the combustion zone to track spatial fluctuations in the flame. The probe is capable of nanosecond time response and is usually slowed electronically to fit the flame characteristics. The probe is a sapphire rod in a stainless steel tube which may be inserted into the combustion chamber and pointed at the flame zone. The end of the sapphire rod is retracted into the SS tube to define a narrow optical collection cone. The collection cone may be adjusted to fit the experiment. The fluorescence signal is collected by the sapphire rod and transmitted through a UV transmitting, fused silica, fiber optic to the detector assembly. The detector is a side window photomultiplier (PMT) with a 310 run line filter. A Hamamatsu photomultiplier base combined with a integral high voltage power supply permits this to be a low voltage device. Electronic connections include: a power lead from a modular DC power supply for 15 VDC; a control lead for 0-1 volts to control the high voltage level (and therefore gain); and a lead out for the actual signal. All low voltage connections make this a safe and easy to use device while still delivering the sensitivity required.

  14. A peptide probe for the detection of neurokinin-1 receptor by disaggregation enhanced fluorescence and magnetic resonance signals

    PubMed Central

    Wu, Jingxian; Zou, Rongfeng; Wang, Qi; Xue, Yajing; Wei, Ping; Yang, Shiping; Wu, Junchen; Tian, He

    2014-01-01

    We report a novel peptide probe for the detection of neurokinin-1 receptor using disaggregation-caused signal enhancement. The probe was obtained via the aggregation of a modified substance P in a terpyridine-Fe (II) complex with Gd (III)-DOTA into well-defined nanostructures, which effectively weaken ligand fluorescence and slow the exchange rate of inner-sphere water molecules. This probe disaggregates upon binding to the neurokinin-1 receptor and activates the contrast agents to generate a fluorescent signal that positively enhances magnetic resonance imaging contrast and allows for the detection of overexpressed receptors on tumor cells and the identification of lung cancer using serum samples. PMID:25270511

  15. Synergy Between Entry Probes and Orbiters

    NASA Technical Reports Server (NTRS)

    Young, Richard E.

    2005-01-01

    We identify two catagories of probe-orbiter interactions which benefit the science return from a particular mission. The first category is termed "Mission Design Aspects". This category is meant to describe those aspects of the mission design involving the orbiter that affect the science return from the probe(s). The second category of probe-orbiter interaction is termed "Orbiter-Probe Science Interactions", and is meant to include interactions between oribter and probe(s) that directly involve science measurements made from each platform. Two mission related aspects of probe-orbiter interactions are delivery of a probe(s) to the entry site(s) by an orbiter, and communication between each probe and the orbiter. We consider four general probe-orbiter science interactions that greatly enhance, or in certain cases are essential for, the mission science return. The four topics are, global context of the probe entry site(s), ground truth for remote sensing observations of an orbiter, atmospheric composition measurements, and wind measurements.

  16. Extradigital Glomus Tumor of Thigh

    PubMed Central

    Beksaç, Kemal; Dogan, Lutfi; Bozdogan, Nazan; Dilek, Gulay; Akgul, Gokhan Giray; Ozaslan, Cihangir

    2015-01-01

    Glomus tumors are benign neoplasms that arise from neuromyoarterial glomus bodies. They represent around 1–5% of all soft-tissue tumors. High temperature, sensitivity, and pain and localized tenderness are the classical triad of symptoms. Most glomus tumors represent in the subungual area of digits. Extradigital glomus tumors are a very rare entity. There are rare cases of these tumors reported to be in shoulder, elbow, knee, wrist, even stomach, colon, and larynx. We are reporting a case of a glomus tumor on thigh and discuss the histological and immunohistochemical features. PMID:26236537

  17. [Benign bone forming tumors].

    PubMed

    Caufourier, C; Leprovost, N; Guillou-Jamard, M-R; Compère, J-F; Bénateau, H

    2009-09-01

    Benign bone forming tumors typically produce dense bone (osteoma, enostosis) or osteoid tissue (osteoid osteoma, osteoblastoma). Even though these four lesions have distinct characteristics, it is sometimes difficult to tell them apart and to rule out malignant bone forming lesions such as osteosarcoma. The first line treatment is surgical exeresis.

  18. Tumor Treated by Endoscopy

    PubMed Central

    Choi, Young; Kwak, Jae Man; Chung, So Hak; Jung, Gu Hee

    2014-01-01

    Background This study was conducted to examine the clinical usefulness and efficacy of endoscopic curettage on benign bone tumor. Methods Thirty-two patients (20 men and 12 women) with benign bone tumor were included in the study. The patients were aged between five and 76 years; the mean follow-up period was 27.05 months (range, 9.6 to 39.9 months). The primary sites include simple bone cyst (9 cases), fibrous dysplasia (6 cases), enchondroma (5 cases), non-ossifying fibroma (4 cases), bone infarct (3 cases), aneurysmal bone cyst (1 case), chondroblastoma (1 case), osteoblastoma (1 case), intraosseous lipoma (1 case), and Brodie abscess (1 case). A plain radiography was performed to assess the radiological recovery. Radiological outcomes, including local recurrence and bone union, were evaluated as excellent, good, poor, and recurred. Results In our series, there were 27 cases (84.4%) of good or better outcomes, six cases (18.8%) of complications (4 local recurrence, 1 wound infection, and 1 pathologic fracture). Conclusions Our results showed that endoscopic curettage and bone graft had a lower rate of recurrence and a higher cure rate in cases of benign bone tumor. It can, therefore, be concluded that endoscopic curettage and bone graft might be good treatment modalities for benign bone tumors. PMID:24605192

  19. Benign small bowel tumor.

    PubMed Central

    Wilson, J M; Melvin, D B; Gray, G; Thorbjarnarson, B

    1975-01-01

    The clinical record and histologic sections of 84 cases of benign small bowel tumor are reviewed. Manifestations of systemic diseases, congenital anomalies, and lesions of either the ileocecal valve or periampullary region were excluded. In the same time span there were 96 small bowel malignancies. Clinical presentation, pathologic findings, management and result are compared to the collected published experience of about 2000 cases. There were 36 leiomyomas, 22 lipomas, 9 angiomas, 6 neurofibromas and 4 fibromas. Thirty-six men and 48 women were affected; the majority in their fifth and sixth decade. Seventy-eight were operative and 6 autopsy diagnoses. The most common symptom was obstruction (42%) followed by hemorrhage (34%) and pain (22%), relative frequency differing for the various specific tumors. There were rarely significant physical findings. A diagnosis of small bowel tumor was made radiologically in 30 patients. Because of the nonspecificity of other signs and symptoms, an acute awareness of the possibility of small bowel tumor is mandatory for preoperative anticipation of the diagnosis. Local resection was performed in all with no deaths or significant postoperative complications. PMID:1078626

  20. [Mediastinal germ cell tumors].

    PubMed

    Bremmer, F; Ströbel, P

    2016-09-01

    The mediastinum is among the most frequent anatomic region in which germ cell tumors (GCT) arise, second only to the gonads. Mediastinal GCT (mGCT) account for 16 % of all mediastinal neoplasms. Although the morphology and (according to all available data) the molecular genetics of mediastinal and gonadal GCT are identical, a number of unique aspects exist. There is a highly relevant bi-modal age distribution. In pre-pubertal children of both sexes, mGCT consist exclusively of teratomas and yolk sac tumors. The prognosis is generally favorable with modern treatment. In post-pubertal adults, virtually all patients with malignant mGCT are males; the prognosis is more guarded and depends (among other factors) on the histological GCT components and is similar to GCT in other organs. So-called somatic type malignancies (i. e. clonally related, non-germ cell neoplasias arising in a GCT) are much more frequent in mGCT than in other organs, and the association between mediastinal yolk sac tumors and hematological malignancies, such as myelodysplasias and leukemias, is unique to mediastinal tumors. The prognosis of GCT with somatic type malignancies is generally dismal. PMID:27491549

  1. Testicular germ cell tumors.

    PubMed

    Looijenga, Leendert H J

    2014-02-01

    Human germ cell tumors are of interest because of their epidemiology, clinical behavior and pathobiology. Histologically, they are subdivided into various elements, with similarities to embryogenesis. Recent insights resulted in a division of five types of human germ cell tumors. In the context of male germ cells, three are relevant; Type I: teratomas and yolk sac tumors of neonates and infants; Type II: seminomas and nonseminomas of (predominantly) adolescents and adults; and Type III: spermatocytic seminomas of the elderly. Recent studies led to significant increases in understanding of the parameters involved in the earliest pathogenetic steps of human germ cells tumors, in particularly the seminomas and nonseminomas (Type II). In case of a disturbed gonadal physiology, either due to the germ cell itself, or the micro-environment, embryonic germ cells during a specific window of sensitization can be blocked in their maturation, resulting in carcinoma in situ or gonadoblastoma, the precursors of seminomas and nonseminomas. The level of testicularization of the gonad determines the histological composition of the precursor. These insights will allow better definition of individuals at risk to develop a germ cell malignancy, with putative preventive measurements, and allow better selection of scientific approaches to elucidate the pathogenesis. PMID:24683949

  2. Tumor-induced osteomalacia

    PubMed Central

    Chong, William H; Molinolo, Alfredo A; Chen, Clara C; Collins, Michael T

    2012-01-01

    Tumor-induced osteomalacia (TIO) is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is high blood levels of the recently identified phosphate and vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23). In TIO, FGF23 is secreted by mesenchymal tumors that are usually benign, but are typically very small and difficult to locate. FGF23 acts primarily at the renal tubule and impairs phosphate reabsorption and 1α-hydroxylation of 25-hydroxyvitamin D, leading to hypophosphatemia and low levels of 1,25-dihydroxy vitamin D. A step-wise approach utilizing functional imaging (F-18 fluorodeoxyglucose positron emission tomography and octreotide scintigraphy) followed by anatomical imaging (computed tomography and/or magnetic resonance imaging), and, if needed, selective venous sampling with measurement of FGF23 is usually successful in locating the tumors. For tumors that cannot be located, medical treatment with phosphate supplements and active vitamin D (calcitriol or alphacalcidiol) is usually successful; however, the medical regimen can be cumbersome and associated with complications. This review summarizes the current understanding of the pathophysiology of the disease and provides guidance in evaluating and treating these patients. Novel imaging modalities and medical treatments, which hold promise for the future, are also reviewed. PMID:21490240

  3. Benign tumors

    Cancer.gov

    In human pulmonary pathology, benign tumors are rare and almost never progress to malignancy. The situation is quite different in mouse pathology, where a significant number of adenomas, especially after some chemical induction schemes and genetic modifications, may progress to carcinomas.

  4. SALIVARY GLAND TUMORS

    PubMed Central

    Sharp, George S.; Helsper, James T.

    1960-01-01

    In a review of a series of 248 salivary gland tumors, seen over a 28-year period, all pathologic material was brought up to date by reclassification according to more recent criteria and nomenclature. In parotid tumors, a probable lowered recurrence rate and a definite decrease in incidence of permanent facial nerve paralysis was found in the more recent cases in which the “Y” incision was used, with identification of the seventh nerve as it leaves the stylomastoid foramen. The five-year recurrence rate for primary mixed tumor was 8.3 per cent, and in recurrent cases it was found to be 18.1 per cent. Of 44 patients with malignant salivary gland tumors in all sites who were observed for five years or more, 32 or 72.7 per cent survived five years. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7.Figure 8.Figure 9.Figure 10.Figure 11.Figure 12. PMID:18732337

  5. Serodiagnosis for Tumor Viruses

    PubMed Central

    Morrison, Brian J.; Labo, Nazzarena; Miley, Wendell J.; Whitby, Denise

    2015-01-01

    The known human tumor viruses include the DNA viruses Epstein-Barr virus, Kaposi sarcoma herpesvirus, Merkel cell polyomavirus, human papillomavirus, and hepatitis B virus. RNA tumor viruses include Human T-cell lymphotrophic virus type-1 and hepatitis C virus. The serological identification of antigens/antibodies in plasma serum is a rapidly progressing field with utility for both scientists and clinicians. Serology is useful for conducting seroepidemiology studies and to inform on the pathogenesis and host immune response to a particular viral agent. Clinically, serology is useful for diagnosing current or past infection and for aiding in clinical management decisions. Serology is useful for screening blood donations for infectious agents and for monitoring the outcome of vaccination against these viruses. Serodiagnosis of human tumor viruses has improved in recent years with increased specificity and sensitivity of the assays, as well as reductions in cost and the ability to assess multiple antibody/antigens in single assays. Serodiagnosis of tumor viruses plays an important role in our understanding of the prevalence and transmission of these viruses and ultimately in the ability to develop treatments/preventions for these globally important diseases. PMID:25843726

  6. Brain tumor stem cells.

    PubMed

    Palm, Thomas; Schwamborn, Jens C

    2010-06-01

    Since the end of the 'no-new-neuron' theory, emerging evidence from multiple studies has supported the existence of stem cells in neurogenic areas of the adult brain. Along with this discovery, neural stem cells became candidate cells being at the origin of brain tumors. In fact, it has been demonstrated that molecular mechanisms controlling self-renewal and differentiation are shared between brain tumor stem cells and neural stem cells and that corruption of genes implicated in these pathways can direct tumor growth. In this regard, future anticancer approaches could be inspired by uncovering such redundancies and setting up treatments leading to exhaustion of the cancer stem cell pool. However, deleterious effects on (normal) neural stem cells should be minimized. Such therapeutic models underline the importance to study the cellular mechanisms implicated in fate decisions of neural stem cells and the oncogenic derivation of adult brain cells. In this review, we discuss the putative origins of brain tumor stem cells and their possible implications on future therapies.

  7. Activatable iRGD-based peptide monolith: Targeting, internalization, and fluorescence activation for precise tumor imaging.

    PubMed

    Cho, Hong-Jun; Lee, Sung-Jin; Park, Sung-Jun; Paik, Chang H; Lee, Sang-Myung; Kim, Sehoon; Lee, Yoon-Sik

    2016-09-10

    A disulfide-bridged cyclic RGD peptide, named iRGD (internalizing RGD, c(CRGDK/RGPD/EC)), is known to facilitate tumor targeting as well as tissue penetration. After the RGD motif-induced targeting on αv integrins expressed near tumor tissue, iRGD encounters proteolytic cleavage to expose the CendR motif that promotes penetration into cancer cells via the interaction with neuropilin-1. Based on these proteolytic cleavage and internalization mechanism, we designed an iRGD-based monolithic imaging probe that integrates multiple functions (cancer-specific targeting, internalization and fluorescence activation) within a small peptide framework. To provide the capability of activatable fluorescence signaling, we conjugated a fluorescent dye to the N-terminal of iRGD, which was linked to the internalizing sequence (CendR motif), and a quencher to the opposite C-terminal. It turned out that fluorescence activation of the dye/quencher-conjugated monolithic peptide probe requires dual (reductive and proteolytic) cleavages on both disulfide and amide bond of iRGD peptide. Furthermore, the cleavage of the iRGD peptide leading to fluorescence recovery was indeed operative depending on the tumor-related angiogenic receptors (αvβ3 integrin and neuropilin-1) in vitro as well as in vivo. Compared to an 'always fluorescent' iRGD control probe without quencher conjugation, the dye/quencher-conjugated activatable monolithic peptide probe visualized tumor regions more precisely with lower background noise after intravenous injection, owing to the multifunctional responses specific to tumor microenvironment. All these results, along with minimal in vitro and in vivo toxicity profiles, suggest potential of the iRGD-based activatable monolithic peptide probe as a promising imaging agent for precise tumor diagnosis. PMID:27349354

  8. Activatable iRGD-based peptide monolith: Targeting, internalization, and fluorescence activation for precise tumor imaging.

    PubMed

    Cho, Hong-Jun; Lee, Sung-Jin; Park, Sung-Jun; Paik, Chang H; Lee, Sang-Myung; Kim, Sehoon; Lee, Yoon-Sik

    2016-09-10

    A disulfide-bridged cyclic RGD peptide, named iRGD (internalizing RGD, c(CRGDK/RGPD/EC)), is known to facilitate tumor targeting as well as tissue penetration. After the RGD motif-induced targeting on αv integrins expressed near tumor tissue, iRGD encounters proteolytic cleavage to expose the CendR motif that promotes penetration into cancer cells via the interaction with neuropilin-1. Based on these proteolytic cleavage and internalization mechanism, we designed an iRGD-based monolithic imaging probe that integrates multiple functions (cancer-specific targeting, internalization and fluorescence activation) within a small peptide framework. To provide the capability of activatable fluorescence signaling, we conjugated a fluorescent dye to the N-terminal of iRGD, which was linked to the internalizing sequence (CendR motif), and a quencher to the opposite C-terminal. It turned out that fluorescence activation of the dye/quencher-conjugated monolithic peptide probe requires dual (reductive and proteolytic) cleavages on both disulfide and amide bond of iRGD peptide. Furthermore, the cleavage of the iRGD peptide leading to fluorescence recovery was indeed operative depending on the tumor-related angiogenic receptors (αvβ3 integrin and neuropilin-1) in vitro as well as in vivo. Compared to an 'always fluorescent' iRGD control probe without quencher conjugation, the dye/quencher-conjugated activatable monolithic peptide probe visualized tumor regions more precisely with lower background noise after intravenous injection, owing to the multifunctional responses specific to tumor microenvironment. All these results, along with minimal in vitro and in vivo toxicity profiles, suggest potential of the iRGD-based activatable monolithic peptide probe as a promising imaging agent for precise tumor diagnosis.

  9. All-fiber probe for laser-induced thermotherapy with integrated temperature measurement capabilities

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Chen, W.; Yu, H.; Gassino, R.; Braglia, A.; Olivero, M.; Perrone, Guido; Vallan, A.

    2015-03-01

    The paper presents our recent results towards the development of a miniaturized all-fiber probe for laser induced thermal ablation of tumor cells, which combines the optimal delivery of a near-infrared high power ablating beam, a low power visible aiming beam and fast Bragg grating (FBG) temperature sensors. Specific combiner and probe end-cap based on dual cladding fibers have been developed to allow the simultaneous handling of the laser beams and of the signal that feeds the temperature sensor. Moreover, a very fast FBG interrogation system has been implemented to track abrupt temperature variations during medical treatment.

  10. Neptune Polar Orbiter with Probes

    NASA Technical Reports Server (NTRS)

    Bienstock, Bernard; Atkinson, David; Baines, Kevin; Mahaffy, Paul; Steffes, Paul; Atreya, Sushil; Stern, Alan; Wright, Michael; Willenberg, Harvey; Smith, David; Frampton, Robert; Sichi, Steve; Peltz, Leora; Masciarelli, James; VanCleve, Jeffey

    2005-01-01

    The giant planets of the outer solar system divide into two distinct classes: the gas giants Jupiter and Saturn, which consist mainly of hydrogen and helium; and the ice giants Uranus and Neptune, which are believed to contain significant amounts of the heavier elements oxygen, nitrogen, and carbon and sulfur. Detailed comparisons of the internal structures and compositions of the gas giants with those of the ice giants will yield valuable insights into the processes that formed the solar system and, perhaps, other planetary systems. By 2012, Galileo, Cassini and possibly a Jupiter Orbiter mission with microwave radiometers, Juno, in the New Frontiers program, will have yielded significant information on the chemical and physical properties of Jupiter and Saturn. A Neptune Orbiter with Probes (NOP) mission would deliver the corresponding key data for an ice giant planet. Such a mission would ideally study the deep Neptune atmosphere to pressures approaching and possibly exceeding 1000 bars, as well as the rings, Triton, Nereid, and Neptune s other icy satellites. A potential source of power would be nuclear electric propulsion (NEP). Such an ambitious mission requires that a number of technical issues be investigated, however, including: (1) atmospheric entry probe thermal protection system (TPS) design, (2) probe structural design including seals, windows, penetrations and pressure vessel, (3) digital, RF subsystem, and overall communication link design for long term operation in the very extreme environment of Neptune's deep atmosphere, (4) trajectory design allowing probe release on a trajectory to impact Neptune while allowing the spacecraft to achieve a polar orbit of Neptune, (5) and finally the suite of science instruments enabled by the probe technology to explore the depths of the Neptune atmosphere. Another driving factor in the design of the Orbiter and Probes is the necessity to maintain a fully operational flight system during the lengthy transit time

  11. Cantilevered probe detector with piezoelectric element

    SciTech Connect

    Adams, Jesse D; Sulchek, Todd A; Feigin, Stuart C

    2014-04-29

    A disclosed chemical detection system for detecting a target material, such as an explosive material, can include a cantilevered probe, a probe heater coupled to the cantilevered probe, and a piezoelectric element disposed on the cantilevered probe. The piezoelectric element can be configured as a detector and/or an actuator. Detection can include, for example, detecting a movement of the cantilevered probe or a property of the cantilevered probe. The movement or a change in the property of the cantilevered probe can occur, for example, by adsorption of the target material, desorption of the target material, reaction of the target material and/or phase change of the target material. Examples of detectable movements and properties include temperature shifts, impedance shifts, and resonant frequency shifts of the cantilevered probe. The overall chemical detection system can be incorporated, for example, into a handheld explosive material detection system.

  12. Cantilevered probe detector with piezoelectric element

    SciTech Connect

    Adams, Jesse D; Sulchek, Todd A; Feigin, Stuart C

    2013-04-30

    A disclosed chemical detection system for detecting a target material, such as an explosive material, can include a cantilevered probe, a probe heater coupled to the cantilevered probe, and a piezoelectric element disposed on the cantilevered probe. The piezoelectric element can be configured as a detector and/or an actuator. Detection can include, for example, detecting a movement of the cantilevered probe or a property of the cantilevered probe. The movement or a change in the property of the cantilevered probe can occur, for example, by adsorption of the target material, desorption of the target material, reaction of the target material and/or phase change of the target material. Examples of detectable movements and properties include temperature shifts, impedance shifts, and resonant frequency shifts of the cantilevered probe. The overall chemical detection system can be incorporated, for example, into a handheld explosive material detection system.

  13. Overview of Probe-based Storage Technologies.

    PubMed

    Wang, Lei; Yang, Ci Hui; Wen, Jing; Gong, Si Di; Peng, Yuan Xiu

    2016-12-01

    The current world is in the age of big data where the total amount of global digital data is growing up at an incredible rate. This indeed necessitates a drastic enhancement on the capacity of conventional data storage devices that are, however, suffering from their respective physical drawbacks. Under this circumstance, it is essential to aggressively explore and develop alternative promising mass storage devices, leading to the presence of probe-based storage devices. In this paper, the physical principles and the current status of several different probe storage devices, including thermo-mechanical probe memory, magnetic probe memory, ferroelectric probe memory, and phase-change probe memory, are reviewed in details, as well as their respective merits and weakness. This paper provides an overview of the emerging probe memories potentially for next generation storage device so as to motivate the exploration of more innovative technologies to push forward the development of the probe storage devices. PMID:27456500

  14. Overview of Probe-based Storage Technologies

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Yang, Ci Hui; Wen, Jing; Gong, Si Di; Peng, Yuan Xiu

    2016-07-01

    The current world is in the age of big data where the total amount of global digital data is growing up at an incredible rate. This indeed necessitates a drastic enhancement on the capacity of conventional data storage devices that are, however, suffering from their respective physical drawbacks. Under this circumstance, it is essential to aggressively explore and develop alternative promising mass storage devices, leading to the presence of probe-based storage devices. In this paper, the physical principles and the current status of several different probe storage devices, including thermo-mechanical probe memory, magnetic probe memory, ferroelectric probe memory, and phase-change probe memory, are reviewed in details, as well as their respective merits and weakness. This paper provides an overview of the emerging probe memories potentially for next generation storage device so as to motivate the exploration of more innovative technologies to push forward the development of the probe storage devices.

  15. Cantilevered probe detector with piezoelectric element

    DOEpatents

    Adams, Jesse D.; Sulchek, Todd A.; Feigin, Stuart C.

    2010-04-06

    A disclosed chemical detection system for detecting a target material, such as an explosive material, can include a cantilevered probe, a probe heater coupled to the cantilevered probe, and a piezoelectric element disposed on the cantilevered probe. The piezoelectric element can be configured as a detector and/or an actuator. Detection can include, for example, detecting a movement of the cantilevered probe or a property of the cantilevered probe. The movement or a change in the property of the cantilevered probe can occur, for example, by adsorption of the target material, desorption of the target material, reaction of the target material and/or phase change of the target material. Examples of detectable movements and properties include temperature shifts, impedance shifts, and resonant frequency shifts of the cantilevered probe. The overall chemical detection system can be incorporated, for example, into a handheld explosive material detection system.

  16. Further capacitive imaging experiments using modified probes

    NASA Astrophysics Data System (ADS)

    Yin, Xiaokang; Li, Zhen; Yan, An; Li, Wei; Chen, Guoming; Hutchins, David A.

    2016-02-01

    In recent years, capacitive imaging (CI) is growing in popularity within the NDE communities, as it has the potential to test materials and structures for defects that are not easily tested by other techniques. In previous work, The CI technique has been successfully used on a various types of materials, including concrete, glass/carbon fibre composite, steel, etc. In such CI experiments, the probes are normally with symmetric or concentric electrodes etched onto PCBs. In addition to these conventional coplanar PCB probes, modified geometries can be made and they can lead to different applications. A brief overview of these modified probes, including high resolution surface imaging probe, combined CI/eddy current probe, and CI probe using an oscilloscope probe as the sensing electrode, is presented in this work. The potential applications brought by these probes are also discussed.

  17. Cantilevered probe detector with piezoelectric element

    DOEpatents

    Adams, Jesse D.; Sulchek, Todd A.; Feigin, Stuart C.

    2012-07-10

    A disclosed chemical detection system for detecting a target material, such as an explosive material, can include a cantilevered probe, a probe heater coupled to the cantilevered probe, and a piezoelectric element disposed on the cantilevered probe. The piezoelectric element can be configured as a detector and/or an actuator. Detection can include, for example, detecting a movement of the cantilevered probe or a property of the cantilevered probe. The movement or a change in the property of the cantilevered probe can occur, for example, by adsorption of the target material, desorption of the target material, reaction of the target material and/or phase change of the target material. Examples of detectable movements and properties include temperature shifts, impedance shifts, and resonant frequency shifts of the cantilevered probe. The overall chemical detection system can be incorporated, for example, into a handheld explosive material detection system.

  18. Imaging hypoxia in tumors.

    PubMed

    Ballinger, J R

    2001-10-01

    For many years, it has been known that hypoxia affects the response to radiotherapy in human cancers. Hypoxic regions can develop as a tumor grows beyond the ability of its blood supply to deliver oxygen to the full extent of the tumor, exacerbated by vascular spasm or compression caused by increased interstitial fluid pressure. However, hypoxia is heterogeneous, and tumors that appear identical by clinical and radiographic criteria can vary greatly in their extent of hypoxia. Several invasive procedures to measure hypoxia in tumors have been developed and are predictive of response to therapy, but none of these is in routine clinical use because of technical complexity, inconvenience, and inability to obtain repeated measures. Noninvasive imaging with a hypoxia-directed radiopharmaceutical could be of great clinical utility. Most such radiopharmaceuticals under development use 2-nitroimidazole as the targeting moiety. 2-Nitroimidazole, which is selectively reduced and bound in hypoxic tissues, has been labeled with F-18, Cu-64/67, I-123, and Tc-99m. Of these, F-18-fluoromisonidazole and I-123-iodoazomycin arabinoside (IAZA) have been most widely studied clinically. Non-nitro-containing bioreductive complexes, such as the Cu-60/62/64 thiosemicarbazone ATSM and Tc-99m butylene amineoxime (BnAO or HL91), have also been evaluated. In particular, 1-123-IAZA and Cu-60-ATSM have shown correlation with response to radiotherapy in preliminary clinical studies. However, more preclinical studies comparing imaging with validated invasive methods and clinical studies with outcome measures are required. Nuclear medicine is poised to play an important role in optimizing the therapy of patients with hypoxic tumors.

  19. Where do pulse oximeter probes break?

    PubMed

    Crede, S; Van der Merwe, G; Hutchinson, J; Woods, D; Karlen, W; Lawn, J

    2014-06-01

    Pulse oximetry, a non-invasive method for accurate assessment of blood oxygen saturation (SPO2), is an important monitoring tool in health care facilities. However, it is often not available in many low-resource settings, due to expense, overly sophisticated design, a lack of organised procurement systems and inadequate medical device management and maintenance structures. Furthermore medical devices are often fragile and not designed to withstand the conditions of low-resource settings. In order to design a probe, better suited to the needs of health care facilities in low-resource settings this study aimed to document the site and nature of pulse oximeter probe breakages in a range of different probe designs in a low to middle income country. A retrospective review of job cards relating to the assessment and repair of damaged or faulty pulse oximeter probes was conducted at a medical device repair company based in Cape Town, South Africa, specializing in pulse oximeter probe repairs. 1,840 job cards relating to the assessment and repair of pulse oximeter probes were reviewed. 60.2 % of probes sent for assessment were finger-clip probes. For all probes, excluding the neonatal wrap probes, the most common point of failure was the probe wiring (>50 %). The neonatal wrap most commonly failed at the strap (51.5 %). The total cost for quoting on the broken pulse oximeter probes and for the subsequent repair of devices, excluding replacement components, amounted to an estimated ZAR 738,810 (USD $98,508). Improving the probe wiring would increase the life span of pulse oximeter probes. Increasing the life span of probes will make pulse oximetry more affordable and accessible. This is of high priority in low-resource settings where frequent repair or replacement of probes is unaffordable or impossible.

  20. 64Cu-labeled phosphonium cations as PET radiotracers for tumor imaging.

    PubMed

    Zhou, Yang; Liu, Shuang

    2011-08-17

    Alteration in mitochondrial transmembrane potential (ΔΨ(m)) is an important characteristic of cancer. The observation that the enhanced negative mitochondrial potential is prevalent in tumor cell phenotype provides a conceptual basis for development of mitochondrion-targeting therapeutic drugs and molecular imaging probes. Since plasma and mitochondrial potentials are negative, many delocalized organic cations, such as rhodamine-123 and (3)H-tetraphenylphosphonium, are electrophoretically driven through these membranes, and able to localize in the energized mitochondria of tumor cells. Cationic radiotracers, such as (99m)Tc-Sestamibi and (99m)Tc-Tetrofosmin, have been clinically used for diagnosis of cancer by single photon emission computed tomography (SPECT) and noninvasive monitoring of the multidrug resistance (MDR) transport function in tumors of different origin. However, their diagnostic and prognostic values are often limited due to their insufficient tumor localization (low radiotracer tumor uptake) and high radioactivity accumulation in the chest and abdominal regions (low tumor selectivity). In contrast, the (64)Cu-labeled phosphonium cations represent a new class of PET (positron emission tomography) radiotracers with good tumor uptake and high tumor selectivity. This review article will focus on our recent experiences in evaluation of (64)Cu-labeled phosphonium cations as potential PET radiotracers. The main objective is to illustrate the impact of radiometal chelate on physical, chemical, and biological properties of (64)Cu radiotracers. It will also discuss some important issues related to their tumor selectivity and possible tumor localization mechanism.

  1. Dual FISH analysis of benign and malignant tumors of the salivary glands and paranasal sinuses.

    PubMed

    Götte, Karl; Ganssmann, Stefan; Affolter, Annette; Schäfer, Carsten; Riedel, Frank; Arens, Norbert; Finger, Sonja; Hörmann, Karl

    2005-11-01

    To date, the underlying genomic changes in benign and malignant tumors of salivary-gland and paranasal-sinus origin are poorly understood. This is due in part to the low incidence of these tumors and the enormous histological variety of tumors within this head and neck region. We examined 58 of these tumors (14 adenoid cystic carcinomas, 9 adenocarcinomas, 5 cylindrical carcinomas, 11 pleomorphic adenomas, and 19 inverted papillomas) by dual fluorescence in situ hybridization (FISH) with centromere-specific probes on six chromosomes (3, 7, 9, 11, 17, and 18) for numerical changes. In adenoid cystic carcinomas, monosomy of chromosome 17 and polysomy of chromosomes 3, 9 and 11 were most frequently encountered. In adenocarcinomas, monosomy of chromosome 17 and polysomy of chromosomes 7 and 11 were most frequent. In cylindrical cell carcinomas, polysomy of chromosomes 7, 9, 11 and 17 was present in the majority of tumors. Disomy is rare, even in benign tumors. Polysomy is more frequent in malignant tumors than in benign. Tetrasomy is found almost only in malignant tumors. In summary, the occurrence of polysomy might reflect a step towards malignancy in tumors of the salivary glands and paranasal mucosa. Polysomy of chromosome 11 could be defined as typical for all investigated histological types of malignant tumor in this region of the head and neck. PMID:16211271

  2. Radiation-Associated Breast Tumors Display a Distinct Gene Expression Profile

    SciTech Connect

    Broeks, Annegien; Braaf, Linde M.; Wessels, Lodewyk F.A.; Vijver, Marc van de; De Bruin, Marie L.; Stovall, Marilyn; Russell, Nicola S.; Leeuwen, Flora E. van; Van't Veer, Laura J.

    2010-02-01

    Purpose: Women who received irradiation for Hodgkin's lymphoma have a strong increased risk for developing breast cancer. Approximately 90% of the breast cancers in these patients can be attributed to their radiation treatment, rendering such series extremely useful to determine whether a common radiation-associated cause underlies the carcinogenic process. Methods and Materials: In this study we used gene expression profiling technology to assess gene expression changes in radiation-associated breast tumors compared with a set of control breast tumors of women unexposed to radiation, diagnosed at the same age. RNA was obtained from fresh frozen tissue samples from 22 patients who developed breast cancer after Hodgkin's lymphoma (BfHL) and from 20 control breast tumors. Results: Unsupervised hierarchical clustering of the profile data resulted in a clustering of the radiation-associated tumors separate from the control tumors (p < 0.001). Using a supervised class prediction tool, a nearest centroid classifier of 198 probes was identified. The BfHL tumors were often of the intrinsic basal breast tumor subtype, and they showed a chromosomal instability profile and a higher expression of the proliferation marker Ki-67. Conclusion: These results indicate that radiation-associated tumors are different from other breast tumors on the basis of their expression profile and that they are mainly of one specific cause that is characterized by high proliferation and a more aggressive tumor type.

  3. Dual targeting for metastatic breast cancer and tumor neovasculature by EphA2-mediated nanocarriers.

    PubMed

    Guo, Zhaoming; He, Bing; Yuan, Lan; Dai, Wenbing; Zhang, Hua; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Zhang, Qiang

    2015-09-30

    EphA2 is a transmembrane receptor tyrosine kinase that is highly expressed on both tumor neovasculature and some kinds of tumor cells. Here, a homing peptide with a sequence of YSAYPDSVPMMSK (YSA) that binds specifically with EphA2 was utilized to modify the stealth liposomes (YSA-LP). With a particle size of about 85 nm, this functionalized nanocarrier was loaded with fluorescent probe or doxorubicin (DOX) and investigated in vitro and in vivo. In the cellular endocytosis studies in vitro, coumarin-6 loaded YSA-LP exhibited significant specificity to both EphA2-overexpressing tumor cells (MDA-MB-231) and human umbilical vein endothelial cells (HUVEC) via a YSA mediated interaction. In a MDA-MB-231 xenograft tumor mouse model, DiR-loaded YSA-LP showed more lasting accumulation in tumor tissue by small animal imaging compared to unmodified liposomes (LP). Further, YSA-LP greatly facilitated the efficacy of DOX loaded against both tumor cells and tumor angiogenesis in the same mouse model, evidenced by inhibiting tumor growth, metastasis and CD31 expression as well as inducing cancer cell apoptosis. Additionally, YSA-LP (DOX) showed relatively low systemic and cardiac toxicity compared with control groups. In conclusion, YSA might be a promising targeting motif for EphA2-overexpressing tumor cells and tumor neovasculature, which could be used to mediate drug delivery for chemotherapy agents. PMID:26004003

  4. Metalloprotein-based MRI probes

    PubMed Central

    Matsumoto, Yuri; Jasanoff, Alan

    2013-01-01

    Metalloproteins have long been recognized as key determinants of endogenous contrast in magnetic resonance imaging (MRI) of biological subjects. More recently, both natural and engineered metalloproteins have been harnessed as biotechnological tools to probe gene expression, enzyme activity, and analyte concentrations by MRI. Metalloprotein MRI probes are paramagnetic and function by analogous mechanisms to conventional gadolinium or iron oxide-based MRI contrast agents. Compared with synthetic agents, metalloproteins typically offer worse sensitivity, but the possibilities of using protein engineering and targeted gene expression approaches in conjunction with metalloprotein contrast agents are powerful and sometimes definitive strengths. This review summarizes theoretical and practical aspects of metalloprotein-based contrast agents, and discusses progress in the exploitation of these proteins for molecular imaging applications. PMID:23376346

  5. Metalloprotein-based MRI probes.

    PubMed

    Matsumoto, Yuri; Jasanoff, Alan

    2013-04-17

    Metalloproteins have long been recognized as key determinants of endogenous contrast in magnetic resonance imaging (MRI) of biological subjects. More recently, both natural and engineered metalloproteins have been harnessed as biotechnological tools to probe gene expression, enzyme activity, and analyte concentrations by MRI. Metalloprotein MRI probes are paramagnetic and function by analogous mechanisms to conventional gadolinium or iron oxide-based MRI contrast agents. Compared with synthetic agents, metalloproteins typically offer worse sensitivity, but the possibilities of using protein engineering and targeted gene expression approaches in conjunction with metalloprotein contrast agents are powerful and sometimes definitive strengths. This review summarizes theoretical and practical aspects of metalloprotein-based contrast agents, and discusses progress in the exploitation of these proteins for molecular imaging applications.

  6. Probing zeolites by vibrational spectroscopies.

    PubMed

    Bordiga, Silvia; Lamberti, Carlo; Bonino, Francesca; Travert, Arnaud; Thibault-Starzyk, Frédéric

    2015-10-21

    This review addresses the most relevant aspects of vibrational spectroscopies (IR, Raman and INS) applied to zeolites and zeotype materials. Surface Brønsted and Lewis acidity and surface basicity are treated in detail. The role of probe molecules and the relevance of tuning both the proton affinity and the steric hindrance of the probe to fully understand and map the complex site population present inside microporous materials are critically discussed. A detailed description of the methods needed to precisely determine the IR absorption coefficients is given, making IR a quantitative technique. The thermodynamic parameters of the adsorption process that can be extracted from a variable-temperature IR study are described. Finally, cutting-edge space- and time-resolved experiments are reviewed. All aspects are discussed by reporting relevant examples. When available, the theoretical literature related to the reviewed experimental results is reported to support the interpretation of the vibrational spectra on an atomic level.

  7. Fibre Optic Probes For Ophthalmology

    NASA Astrophysics Data System (ADS)

    Romaniuk, Ryszard S.

    1986-09-01

    One of the most interesting fields of application of optical fibre technology is the medicine. Among other medical disciplines the field of ophthalmology is very interesting for these applications because of optical character of the organ of vision. After some remarks of a general nature, and concerning the needs of modern ophthalmology, we will review here our trials to apply optical fibre devices for the optical surgery, therapy and diagnosis in the ophthalmology. The devices include: optical fibre illuminators for the applications with operational probes (crioprobes, termal probes, a vitrotom etc.) and some of the diagnostic equipment (like Goldman lens etc.), optical fibre gradient microoptics for delivering of a laser beam to the appropriate internal structures of the eyeglobe, optical fibre lacrimaloscope for the screening of the lacrimal ducts and another one for the orbit. A general conception of the multitask fibre optic microprobe fcr ophthalmological applications - operations and diagnosis/1/ - concludes the work.

  8. Ion beam probe diagnostic system

    NASA Astrophysics Data System (ADS)

    Hickok, R. L.; Jennings, W. C.; Woo, J. T.; Connor, K. A.

    1980-07-01

    Tokomak plasmas suitable for diagnostic development were produced in RENTOR following technological improvements in the vacuum chamber and discharge cleaning systems. Secondary ion signals were obtained from the heavy ion beam probe on RENTOR leading to initial estimates of the plasma space potential, which appears to vary by several hundred volts during the plasma pulse. The principle of measuring space potential in a minimum-B geometry was established using an ion gun mounted at the center of the ALEX baseball coil. The neutral beam probe was installed for measuring the space potential using actual secondary ion signals from a hollow cathode arc in ALEX and preliminary tests have begun. The ion beam test stand was significantly altered to allow more flexibility in testing energy analyzers, ion guns, and ion focusing concepts.

  9. Fabrication of molecular tension probes.

    PubMed

    Kim, Sung Bae; Fujii, Rika

    2016-01-01

    A unique bioluminescent imaging probe is introduced for illuminating molecular tension appended by protein-protein interactions (PPIs) of interest. A full-length luciferase is sandwiched between two proteins of interest via minimal flexible linkers. The ligand-activated PPIs append intramolecular tension to the sandwiched luciferase, boosting or dropping the enzymatic activity in a quantitative manner. This method guides construction of a new lineage of bioassays for determining molecular tension appended by ligand-activated PPIs. The summary of the method is: •Molecular tension appended by protein-protein interactions (PPI) is visualized with a luciferase.•Estrogen activities are quantitatively illuminated with the molecular tension probes.•Full-length Renilla luciferase enhances the optical intensities after bending by PPI.

  10. Fabrication of molecular tension probes

    PubMed Central

    Kim, Sung Bae; Fujii, Rika

    2016-01-01

    A unique bioluminescent imaging probe is introduced for illuminating molecular tension appended by protein–protein interactions (PPIs) of interest. A full-length luciferase is sandwiched between two proteins of interest via minimal flexible linkers. The ligand-activated PPIs append intramolecular tension to the sandwiched luciferase, boosting or dropping the enzymatic activity in a quantitative manner. This method guides construction of a new lineage of bioassays for determining molecular tension appended by ligand-activated PPIs. The summary of the method is: • Molecular tension appended by protein–protein interactions (PPI) is visualized with a luciferase. • Estrogen activities are quantitatively illuminated with the molecular tension probes. • Full-length Renilla luciferase enhances the optical intensities after bending by PPI. PMID:27222821

  11. Lowering photosensitizer doses and increasing fluences induce apoptosis in tumor bearing mice.

    PubMed

    Haedicke, Katja; Graefe, Susanna; Teichgraeber, Ulf; Hilger, Ingrid

    2016-07-01

    The objective of this study was to determine an optimal dose of photodynamic therapy (PDT) for inducing apoptotic tumor cells in vivo. In this context, mice bearing human tongue-squamous epithelium carcinomas were treated with various photosensitizer concentrations and fluences. Tumor apoptosis was imaged after 2 days via a self-designed DY-734-annexin V probe using near-infrared fluorescence (NIRF) optical imaging. Apoptosis was verified ex vivo via TUNEL staining. Apoptotic tumor cells were detected in vivo at a dose of 40 µg photosensitizer and a fluency of 100 J/cm(2). This is the lowest photosensitizer dose reported so far. PMID:27446695

  12. Improved double planar probe data analysis technique

    SciTech Connect

    Ghim, Young-chul; Hershkowitz, Noah

    2009-03-15

    Plasma electron number density and ion number density in a dc multidipole weakly collisional Ar plasma are measured with a single planar Langmuir probe and a double planar probe, respectively. A factor of two discrepancy between the two density measurements is resolved by applying Sheridan's empirical formula [T. E. Sheridan, Phys. Plasmas 7, 3084 (2000)] for sheath expansion to the double probe data.

  13. General Information about Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  14. Treatment Option Overview (Pituitary Tumors)

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  15. Stages of Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... symptoms of GI carcinoid tumors in the jejunum (middle part of the small intestine) and ileum (last part ... Treatment of GI carcinoid tumors in the jejunum (middle part of the small intestine) and ileum (last part ...

  16. Drugs Approved for Brain Tumors

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Brain Tumors This page lists cancer drugs approved by ... that are not listed here. Drugs Approved for Brain Tumors Afinitor (Everolimus) Afinitor Disperz (Everolimus) Avastin (Bevacizumab) ...

  17. Pituitary: Non-Secretory Tumors

    MedlinePlus

    ... categories—tumor mass effects and hyposecretion effects. Tumor mass effects Visual field disturbances, most commonly loss of ... surgery. The goal is to completely remove the mass or cyst and preserve normal pituitary, brain, and ...

  18. Optical probe with reference fiber

    DOEpatents

    Da Silva, Luiz B.; Chase, Charles L.

    2006-03-14

    A system for characterizing tissue includes the steps of generating an emission signal, generating a reference signal, directing the emission signal to and from the tissue, directing the reference signal in a predetermined manner relative to the emission signal, and using the reference signal to compensate the emission signal. In one embodiment compensation is provided for fluctuations in light delivery to the tip of the probe due to cable motion.

  19. Distance Probes of Dark Energy

    SciTech Connect

    Kim, A. G.; Padmanabhan, N.; Aldering, G.; Allen, S. W.; Baltay, C.; Cahn, R. N.; D' Andrea, C. B.; Dalal, N.; Dawson, K. S.; Denney, K. D.; Eisenstein, D. J.; Finley, D. A.; Freedman, W. L.; Ho, S.; Holz, D. E.; Kasen, D.; Kent, S. M.; Kessler, R.; Kuhlmann, S.; Linder, E. V.; Martini, P.; Nugent, P. E.; Perlmutter, S.; Peterson, B. M.; Riess, A. G.; Rubin, D.; Sako, M.; Suntzeff, N. V.; Suzuki, N.; Thomas, R. C.; Wood-Vasey, W. M.; Woosely, S. E.

    2015-03-15

    We present the results from the Distances subgroup of the Cosmic Frontier Community Planning Study (Snowmass 2013). This document summarizes the current state of the field as well as future prospects and challenges. In addition to the established probes using Type Ia supernovae and baryon acoustic oscillations, we also consider prospective methods based on clusters, active galactic nuclei, gravitational wave sirens and strong lensing time delays.

  20. Design, Synthesis and Evaluation of Small Molecule Hsp90 Probes

    PubMed Central

    Taldone, Tony; Zatorska, Danuta; Patel, Pallav D.; Zong, Hongliang; Rodina, Anna; Ahn, James H.; Moulick, Kamalika; Guzman, Monica L.

    2011-01-01

    A number of compounds from different chemical classes are known to bind competitively to the ATP-pocket of Hsp90 and inhibit its chaperone function. The natural product geldanamycin was the first reported inhibitor of Hsp90 and since then synthetic inhibitors from purine, isoxazole and indazol-4-one chemical classes have been discovered and are currently or soon to be in clinical trials for the treatment of cancer. In spite of a similar binding mode to Hsp90, distinct biological profiles were demonstrated amongst these molecules, both in vitro and in vivo. To better understand the molecular basis for these dissimilarities, we report here the synthesis of chemical tools for three Hsp90 inhibitor classes. These agents will be useful for probing tumor-by-tumor the Hsp90 complexes isolated by specific inhibitors. Such information will lead to better understanding of tumor specific molecular markers to aid in their clinical development. It will also help to elucidate the molecular basis for the biological differences observed among Hsp90 inhibitors. PMID:21459002

  1. Intron-Specific Neuropeptide Probes

    PubMed Central

    Gainer, Harold; Ponzio, Todd A.; Yue, Chunmei; Kawasaki, Makoto

    2016-01-01

    Measurements of changes in pre-mRNA levels by intron-specific probes are generally accepted as more closely reflecting changes in gene transcription rates than are measurements of mRNA levels by exonic probes. This is, in part, because the pre-mRNAs, which include the primary transcript and various splicing intermediates located in the nucleus (also referred to as heteronuclear RNAs, or hnRNAs), are processed rapidly (with half-lives <60 min) as compared to neuropeptide mRNAs, which are then transferred to the cytoplasm and which have much longer half-lives (often over days). In this chapter, we describe the use of exon-and intron-specific probes to evaluate oxytocin (OT) and vasopressin (VP) neuropeptide gene expression by analyses of their mRNAs and hnRNAs by quantitative in situ hybridization (qISH) and also by using specific PCR primers in quantitative, real-time PCR (qPCR) procedures. PMID:21922402

  2. Galileo Space Probe News Conference

    NASA Astrophysics Data System (ADS)

    1996-01-01

    This NASA Kennedy Space Center (KSC) video release presents Part 1 of a press conference regarding the successful entry of the Galileo Space Probe into Jupiter's atmosphere. The press conference panel is comprised of twelve principal investigators and project scientists that oversee the Galileo mission. Among these panelists, William J. O'Neil (Jet Propulsion Lab.) begins the video praising all of the scientists that worked on the orbiter mission. He then presents a visual overview of Galileo's overall mission trajectory and schedule. Marcie Smith (NASA Ames Research Center) then describes the Galileo Probe mission and the overall engineering and data acquisition aspects of the Probe's Jupiter atmospheric entry. Dr. Richard Young (NASA Ames Research Center) follows with a brief scientific overview, describing the measurements of the atmospheric composition as well as the instruments that were used to gather the data. Atmospheric pressure, temperature, density, and radiation levels of Jupiter were among the most important parameters measured. It is explained that these measurements would be helpful in determining among other things, the overall dynamic meteorology of Jupiter. A question and answer period follows the individual presentations. Atmospheric thermal structure, water abundances, wind profiles, radiation, cloud structure, chemical composition, and electricity are among the topics discussed. Parts 2 and 3 of the press conference can be found in document numbers NONP-NASA-VT-2000001074, and NONP-NASA-VT-2000001075.

  3. [Osseous tumors of the jaw].

    PubMed

    Reychler, H

    1988-01-01

    The osseous tumors of the jaw bones are relatively rare but very oft malignant. This work analyses the different epidemiological, clinical, radiological, histological and therapeutic features of the benign and malignant osseous tumors of the jaw bones, with regard to the most recent literature. The described benign tumors are the osteoma and osteomatosis, the osteoblastoma and osteoid osteoma, the desmo-osteoblastoma and the exostosis. The osteosarcoma is the unique malignant osseous tumor encountered.

  4. [Tumors of the salivary glands].

    PubMed

    Halimi, P; Gardner, M; Petit, F

    2005-06-01

    Tumors of salivary glands arise mainly from the parotid gland. Magnetic Resonance Imaging (MRI) is mandatory not only to localize precisely the tumor within the gland but also to differentiate between benign and malignant neoplasms, in competition with cytology in fine-needle aspiration biopsy. Tumors without risk of transformation, such as adenolymphoma, are not systematically operated on. Indications of roentgenotherapy and irradiation volumes depend on histologic type, localisation and size of the tumor.

  5. [Tumor of the Parotid Gland].

    PubMed

    Pötzl, Teresa; Iselin, Sabine; Husner, Alexander

    2016-05-11

    Salivary gland tumors are a rare, histologically heterogeneous group of tumors which constitute approximately 4–6 % of all head and neck neoplasms. In 2/3 of cases they are benign, especially in the parotid gland. We report about a rare tumor of the parotid gland presenting as an extraskeletal chondroma. Histologically there were multiple S 100 protein-positive nests of chondrocytes. The externally completed cytology suspected a pleomorphic adenoma, nevertheless, the final histopathological findings showed another tumor entity.

  6. A novel radiofluorinated agouti-related protein for tumor angiogenesis imaging.

    PubMed

    Jiang, Han; Moore, Sarah J; Liu, Shuanglong; Liu, Hongguang; Miao, Zheng; Cochran, Frank V; Liu, Yang; Tian, Mei; Cochran, Jennifer R; Zhang, Hong; Cheng, Zhen

    2013-02-01

    A novel protein scaffold based on the cystine knot domain of the agouti-related protein (AgRP) has been used to engineer mutants that can bind to the α(v)β(3) integrin receptor with high affinity and specificity. In the current study, an (18)F-labeled AgRP mutant (7C) was prepared and evaluated as a positron emission tomography (PET) probe for imaging tumor angiogenesis. AgRP-7C was synthesized by solid phase peptide synthesis and site-specifically conjugated with 4-nitrophenyl 2-(18/19)F-fluoropropionate ((18/19)F-NFP) to produce the fluorinated peptide, (18/19)F-FP-AgRP-7C. Competition binding assays were used to measure the relative affinities of AgRP-7C and (19)F-FP-AgRP-7C to human glioblastoma U87MG cells that overexpress α(v)β(3) integrin. In addition, biodistribution, metabolic stability, and small animal PET imaging studies were conducted with (18)F-FP-AgRP-7C using U87MG tumor-bearing mice. Both AgRP-7C and (19)F-FP-AgRP-7C specifically competed with (125)I-echistatin for binding to U87MG cells with half maximal inhibitory concentration (IC(50)) values of 9.40 and 8.37 nM, respectively. Non-invasive small animal PET imaging revealed that (18)F-FP-AgRP-7C exhibited rapid and good tumor uptake (3.24 percentage injected dose per gram [% ID/g] at 0.5 h post injection [p.i.]). The probe was rapidly cleared from the blood and from most organs, resulting in excellent tumor-to-normal tissue contrasts. Tumor uptake and rapid clearance were further confirmed with biodistribution studies. Furthermore, co-injection of (18)F-FP-AgRP-7C with a large molar excess of blocking peptide c(RGDyK) significantly inhibited tumor uptake in U87MG xenograft models, demonstrating the integrin-targeting specificity of the probe. Metabolite assays showed that the probe had high stability, making it suitable for in vivo applications. (18)F-FP-AgRP-7C exhibits promising in vivo properties such as rapid tumor targeting, good tumor uptake, and excellent tumor-to-normal tissue ratios

  7. Apoptosis in irradiated murine tumors.

    PubMed

    Stephens, L C; Ang, K K; Schultheiss, T E; Milas, L; Meyn, R E

    1991-09-01

    Early radiation responses of transplantable murine ovarian (OCaI) and hepatocellular (HCaI) carcinomas were examined at 6, 24, 48, 96, and 144 h after single photon doses of 25, 35, or 45 Gy. Previous studies using tumor growth delay and tumor radiocurability assays had shown OCaI tumors to be relatively radiosensitive and HCaI tumors to be radioresistant. At 6 h, approximately 20% of nuclei in OCaI tumors showed aberrations characteristic of cell death by apoptosis. This contrasted to an incidence of 3% in HCaI tumors. Mitotic activity was eliminated in OCaI tumors but was only transiently suppressed in HCaI tumors. At 24-96 h, OCaI tumors continued to display apoptosis and progressive necrosis, whereas HCaI tumors responded by exhibiting marked pleomorphism. Factors other than mitotic activity may influence tumor radiosensitivity, and one of these may be susceptibility to induction of apoptosis (programmed cell death), because this was a prominent early radiation response by the radiosensitive OCaI tumors.

  8. Nonodontogenic Tumors of the Jaws.

    PubMed

    Dyalram, Donita; Aslam-Pervez, Nawaf; Lubek, Joshua E

    2016-02-01

    Nonodontogenic tumors of the jaws are common in the pediatric population, accounting for approximately 70% of pediatric jaw tumors. This article focuses on the clinical characteristics and management of the benign nonodontogenic tumors (nonaggressive and aggressive) of the jaws most commonly encountered in children.

  9. Apoptosis in irradiated murine tumors.

    PubMed

    Stephens, L C; Ang, K K; Schultheiss, T E; Milas, L; Meyn, R E

    1991-09-01

    Early radiation responses of transplantable murine ovarian (OCaI) and hepatocellular (HCaI) carcinomas were examined at 6, 24, 48, 96, and 144 h after single photon doses of 25, 35, or 45 Gy. Previous studies using tumor growth delay and tumor radiocurability assays had shown OCaI tumors to be relatively radiosensitive and HCaI tumors to be radioresistant. At 6 h, approximately 20% of nuclei in OCaI tumors showed aberrations characteristic of cell death by apoptosis. This contrasted to an incidence of 3% in HCaI tumors. Mitotic activity was eliminated in OCaI tumors but was only transiently suppressed in HCaI tumors. At 24-96 h, OCaI tumors continued to display apoptosis and progressive necrosis, whereas HCaI tumors responded by exhibiting marked pleomorphism. Factors other than mitotic activity may influence tumor radiosensitivity, and one of these may be susceptibility to induction of apoptosis (programmed cell death), because this was a prominent early radiation response by the radiosensitive OCaI tumors. PMID:1886987

  10. The controversy of Warthin's tumor

    SciTech Connect

    Chapnik, J.S.

    1983-06-01

    Warthin's tumor is controversial. This controversy is multifaceted and relates to all aspects of the tumor from its historical beginnings to its pathogenesis, investigations, and treatments. In this paper, an in depth study of Warthin's tumor has been made to help clarify these controversies.

  11. Tumors of the salivary glands.

    PubMed

    Madani, Gitta; Beale, Timothy

    2006-12-01

    This article reviews the role of imaging in the management of tumors of the salivary glands, discussing tumor localization, extent, and, where possible, characterization. The relative benefits of the different modalities and the typical features of benign and malignant lesions are discussed for each modality. Characteristic appearances of specific tumors are highlighted.

  12. Multimodal in vivo MRI and NIRF imaging of bladder tumor using peptide conjugated glycol chitosan nanoparticles

    NASA Astrophysics Data System (ADS)

    Key, Jaehong; Dhawan, Deepika; Knapp, Deborah W.; Kim, Kwangmeyung; Kwon, Ick Chan; Choi, Kuiwon; Leary, James F.

    2012-03-01

    Exact detection and complete removal of cancer is a key point to minimize cancer recurrence. However, it is currently very difficult to detect small tumors inside human body and continuously monitor tumors using a non-invasive imaging modality. Presently, positron emission tomography (PET) can provide the most sensitive cancer images in the human body. However, PET imaging has very limited imaging time because they typically use isotopes with short halflives. PET imaging cannot also visualize anatomical information. Magnetic resonance imaging (MRI) can provide highresolution images inside the body but it has a low sensitivity, so MRI contrast agents are necessary to enhance the contrast of tumor. Near infrared fluorescent (NIRF) imaging has a good sensitivity to visualize tumor using optical probes, but it has a very limited tissue penetration depth. Therefore, we developed multi-modality nanoparticles for MRI based diagnosis and NIRF imaging based surgery of cancer. We utilized glycol chitosan of 350 nm as a vehicle for MRI contrast agents and NIRF probes. The glycol chitosan nanoparticles were conjugated with NIRF dye, Cy5.5 and bladder cancer targeting peptides to increase the internalization of cancer. For MR contrast effects, iron oxide based 22 nm nanocubes were physically loaded into the glycol chitosan nanoparticles. The nanoparticles were characterized and evaluated in bladder tumor bearing mice. Our study suggests the potential of our nanoparticles by both MRI and NIRF imaging for tumor diagnosis and real-time NIRF image-guided tumor surgery.

  13. Atmospheric entry probes for outer planet exploration. Outer planet entry probe technical summary

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The use of unmanned space probes for investigating the conditions existing on and around the outer planets of the solar system is discussed. The subjects included in the report are: (1) the design of a common entry probe for outer planet missions, (2) the significant trades related to the development of a common probe design, (3) the impact of bus selection on probe design, (4) the impact of probe requirements on bus modifications, and (5) the key technology elements recommended for advanced development. Drawings and illustrations of typical probes are included to show the components and systems used in the space probes.

  14. Microscopic Delineation of Medulloblastoma Margins in a Transgenic Mouse Model Using a Topically Applied VEGFR-1 Probe1

    PubMed Central

    Wang, Danni; Chen, Ye; Leigh, Steven Y; Haeberle, Henry; Contag, Christopher H; Liu, Jonathan T C

    2012-01-01

    The unambiguous demarcation of tumor margins is critical at the final stages in the surgical treatment of brain tumors because patient outcomes have been shown to correlate with the extent of resection. Real-time high-resolution imaging with the aid of a tumor-targeting fluorescent contrast agent has the potential to enable intraoperative differentiation of tumor versus normal tissues with accuracy approaching the current gold standard of histopathology. In this study, a monoclonal antibody targeting the vascular endothelial growth factor receptor 1 (VEGFR-1) was conjugated to fluorophores and evaluated as a tumor contrast agent in a transgenic mouse model of medulloblastoma. The probe was administered topically, and its efficacy as an imaging agent was evaluated in vitro using flow cytometry, as well as ex vivo on fixed and fresh tissues through immunohistochemistry and dual-axis confocal microscopy, respectively. Results show a preferential binding to tumor versus normal tissue, suggesting that a topically applied VEGFR-1 probe can potentially be used with real-time intraoperative optical sectioning microscopy to guide brain tumor resections. PMID:23323155

  15. Hyperdiploid tumor cells increase phenotypic heterogeneity within Glioblastoma tumors.

    PubMed

    Donovan, Prudence; Cato, Kathleen; Legaie, Roxane; Jayalath, Rumal; Olsson, Gemma; Hall, Bruce; Olson, Sarah; Boros, Samuel; Reynolds, Brent A; Harding, Angus

    2014-04-01

    Here we report the identification of a proliferative, viable, and hyperdiploid tumor cell subpopulation present within Glioblastoma (GB) patient tumors. Using xenograft tumor models, we demonstrate that hyperdiploid cell populations are maintained in xenograft tumors and that clonally expanded hyperdiploid cells support tumor formation and progression in vivo. In some patient tumorsphere lines, hyperdiploidy is maintained during long-term culture and in vivo within xenograft tumor models, suggesting that hyperdiploidy can be a stable cell state. In other patient lines hyperdiploid cells display genetic drift in vitro and in vivo, suggesting that in these patients hyperdiploidy is a transient cell state that generates novel phenotypes, potentially facilitating rapid tumor evolution. We show that the hyperdiploid cells are resistant to conventional therapy, in part due to infrequent cell division due to a delay in the G₀/G₁ phase of the cell cycle. Hyperdiploid tumor cells are significantly larger and more metabolically active than euploid cancer cells, and this correlates to an increased sensitivity to the effects of glycolysis inhibition. Together these data identify GB hyperdiploid tumor cells as a potentially important subpopulation of cells that are well positioned to contribute to tumor evolution and disease recurrence in adult brain cancer patients, and suggest tumor metabolism as a promising point of therapeutic intervention against this subpopulation. PMID:24448662

  16. Tumor-Induced Hyperlipidemia Contributes to Tumor Growth

    PubMed Central

    Huang, Jianfeng; Li, Lena; Lian, Jihong; Schauer, Silvia; Vesely, Paul W.; Kratky, Dagmar; Hoefler, Gerald; Lehner, Richard

    2016-01-01

    Summary The known link between obesity and cancer suggests an important interaction between the host lipid metabolism and tumorigenesis. Here, we used a syngeneic tumor graft model to demonstrate that tumor development influences the host lipid metabolism. BCR-Abl-transformed precursor B cell tumors induced hyperlipidemia by stimulating very low-density lipoprotein (VLDL) production and blunting VLDL and low-density lipoprotein (LDL) turnover. To assess whether tumor progression was dependent on tumor-induced hyperlipidemia, we utilized the VLDL production-deficient mouse model, carboxylesterase3/triacylglycerol hydrolase (Ces3/TGH) knockout mice. In Ces3/Tgh–/– tumor-bearing mice, plasma triglyceride and cholesterol levels were attenuated. Importantly tumor weight was reduced in Ces3/Tgh–/– mice. Mechanistically, reduced tumor growth in Ces3/Tgh–/– mice was attributed to reversal of tumor-induced PCSK9-mediated degradation of hepatic LDLR and decrease of LDL turnover. Our data demonstrate that tumor-induced hyperlipidemia encompasses a feed-forward loop that reprograms hepatic lipoprotein homeostasis in part by providing LDL cholesterol to support tumor growth. PMID:27050512

  17. Tumor endothelial marker 1-specific DNA vaccination targets tumor vasculature.

    PubMed

    Facciponte, John G; Ugel, Stefano; De Sanctis, Francesco; Li, Chunsheng; Wang, Liping; Nair, Gautham; Sehgal, Sandy; Raj, Arjun; Matthaiou, Efthymia; Coukos, George; Facciabene, Andrea

    2014-04-01

    Tumor endothelial marker 1 (TEM1; also known as endosialin or CD248) is a protein found on tumor vasculature and in tumor stroma. Here, we tested whether TEM1 has potential as a therapeutic target for cancer immunotherapy by immunizing immunocompetent mice with Tem1 cDNA fused to the minimal domain of the C fragment of tetanus toxoid (referred to herein as Tem1-TT vaccine). Tem1-TT vaccination elicited CD8+ and/or CD4+ T cell responses against immunodominant TEM1 protein sequences. Prophylactic immunization of animals with Tem1-TT prevented or delayed tumor formation in several murine tumor models. Therapeutic vaccination of tumor-bearing mice reduced tumor vascularity, increased infiltration of CD3+ T cells into the tumor, and controlled progression of established tumors. Tem1-TT vaccination also elicited CD8+ cytotoxic T cell responses against murine tumor-specific antigens. Effective Tem1-TT vaccination did not affect angiogenesis-dependent physiological processes, including wound healing and reproduction. Based on these data and the widespread expression of TEM1 on the vasculature of different tumor types, we conclude that targeting TEM1 has therapeutic potential in cancer immunotherapy.

  18. Characterization of the Tumor Secretome from Tumor Interstitial Fluid (TIF).

    PubMed

    Gromov, Pavel; Gromova, Irina

    2016-01-01

    Tumor interstitial fluid (TIF) surrounds and perfuses bodily tumorigenic tissues and cells, and can accumulate by-products of tumors and stromal cells in a relatively local space. Interstitial fluid offers several important advantages for biomarker and therapeutic target discovery, especially for cancer. Here, we describe the most currently accepted method for recovering TIF from tumor and nonmalignant tissues that was initially performed using breast cancer tissue. TIF recovery is achieved by passive extraction of fluid from small, surgically dissected tissue specimens in phosphate-buffered saline. We also present protocols for hematoxylin and eosin (H&E) staining of snap-frozen and formalin-fixed, paraffin-embedded (FFPE) tumor sections and for proteomic profiling of TIF and matched tumor samples by high-resolution two-dimensional gel electrophoresis (2D-PAGE) to enable comparative analysis of tumor secretome and paired tumor tissue.

  19. Characterization of the Tumor Secretome from Tumor Interstitial Fluid (TIF).

    PubMed

    Gromov, Pavel; Gromova, Irina

    2016-01-01

    Tumor interstitial fluid (TIF) surrounds and perfuses bodily tumorigenic tissues and cells, and can accumulate by-products of tumors and stromal cells in a relatively local space. Interstitial fluid offers several important advantages for biomarker and therapeutic target discovery, especially for cancer. Here, we describe the most currently accepted method for recovering TIF from tumor and nonmalignant tissues that was initially performed using breast cancer tissue. TIF recovery is achieved by passive extraction of fluid from small, surgically dissected tissue specimens in phosphate-buffered saline. We also present protocols for hematoxylin and eosin (H&E) staining of snap-frozen and formalin-fixed, paraffin-embedded (FFPE) tumor sections and for proteomic profiling of TIF and matched tumor samples by high-resolution two-dimensional gel electrophoresis (2D-PAGE) to enable comparative analysis of tumor secretome and paired tumor tissue. PMID:27665563

  20. Project Prometheus and Future Entry Probe Missions

    NASA Technical Reports Server (NTRS)

    Spilker, Thomas R.

    2005-01-01

    A viewgraph presentation on project Prometheus and future entry probe missions is shown. The topics include: 1) What Is Project Prometheus?; 2) What Capabilities Can Project Prometheus Offer? What Mission Types Are Being Considered?; 3) Jupiter Icy Moons Orbiter (JIMO); 4) How Are Mission Opportunities Changing?; 5) Missions Of Interest a Year Ago; 6) Missions Now Being Considered For Further Study; 7) Galileo-Style (Conventional) Probe Delivery; 8) Galileo-Style Probe Support; 9) Conventional Delivery and Support of Multiple Probes; 10) How Entry Probe Delivery From an NEP Vehicle Is Different; and 11) Concluding Remarks.

  1. Metallized Capillaries as Probes for Raman Spectroscopy

    NASA Technical Reports Server (NTRS)

    Pelletier, Michael

    2003-01-01

    A class of miniature probes has been proposed to supplant the fiber-optic probes used heretofore in some Raman and fluorescence spectroscopic systems. A probe according to the proposal would include a capillary tube coated with metal on its inside to make it reflective. A microlens would be hermetically sealed onto one end of the tube. A spectroscopic probe head would contain a single such probe, which would both deliver laser light to a sample and collect Raman or fluorescent light emitted by the sample.

  2. pH Meter probe assembly

    DOEpatents

    Hale, C.J.

    1983-11-15

    An assembly for mounting a pH probe in a flowing solution, such as a sanitary sewer line, which prevents the sensitive glass portion of the probe from becoming coated with grease, oil, and other contaminants, whereby the probe gives reliable pH indication over an extended period of time. The pH probe assembly utilizes a special filter media and a timed back-rinse feature for flushing clear surface contaminants of the filter. The flushing liquid is of a known pH and is utilized to check performance of the probe. 1 fig.

  3. pH Meter probe assembly

    DOEpatents

    Hale, Charles J.

    1983-01-01

    An assembly for mounting a pH probe in a flowing solution, such as a sanitary sewer line, which prevents the sensitive glass portion of the probe from becoming coated with grease, oil, and other contaminants, whereby the probe gives reliable pH indication over an extended period of time. The pH probe assembly utilizes a special filter media and a timed back-rinse feature for flushing clear surface contaminants of the filter. The flushing liquid is of a known pH and is utilized to check performance of the probe.

  4. Current to a moving cylindrical electrostatic probe

    NASA Technical Reports Server (NTRS)

    Hoegy, W. R.; Wharton, L. E.

    1972-01-01

    The current collection characteristics of a moving cylindrical Langmuir probe are evaluated for a range of probe speeds and potentials which are applicable to earth and planetary measurements. The current expressions derived include the cases of the general accelerated current, sheath area limited current, orbital motion limited current, and retarded current. For the orbital motion limited current, a simple algebraic expression is obtained which includes and generalizes the Mott-Smith and Langmuir expressions for both a stationary probe and a rapidly moving probe. For a rapidly moving probe a single formula adequately represents both the accelerated and the retarded current.

  5. [HPV contamination of endocavity vaginal ultrasound probes].

    PubMed

    Heard, I; Favre, M

    2015-02-01

    While the use of endovaginal ultrasound probes is increasing, the risk of contamination of women with endocavity vaginal probes was not assessed. In particular, the clinical significance of detection of human papillomavirus (HPV) infection, the most common sexually transmitted viral infection, on endovaginal ultrasound probes is uncertain. The recommendations of good practice for decontamination of these probes developed by the High Council for Public Health and the Academy of Medicine have not been evaluated. The objective of this article was to review recent publications concluding to the detection of HPV and human cellular DNA after gynecological examination and disinfection of vaginal ultrasound probes.

  6. Inflammatory myofibroblastic tumor

    PubMed Central

    Palaskar, Sangeeta; Koshti, Supriya; Maralingannavar, Mahesh; Bartake, Anirudha

    2011-01-01

    Inflammatory myofibroblastic tumor is an uncommon lesion of unknown cause. It encompasses a spectrum of myofibroblastic proliferation along with varying amount of inflammatory infiltrate. A number of terms have been applied to the lesion, namely, inflammatory pseudotumor, fibrous xanthoma, plasma cell granuloma, pseudosarcoma, lymphoid hamartoma, myxoid hamartoma, inflammatory myofibrohistiocytic proliferation, benign myofibroblatoma, and most recently, inflammatory myofibroblastic tumor. The diverse nomenclature is mostly descriptive and reflects the uncertainty regarding true biologic nature of these lesions. Recently, the concept of this lesion being reactive has been challenged based on the clinical demonstration of recurrences and metastasis and cytogenetic evidence of acquired clonal chromosomal abnormalities. We hereby report a case of inflammatory pseudotumor and review its inflammatory versus neoplastic behavior. PMID:22346151

  7. Immunotherapy and tumor microenvironment.

    PubMed

    Tang, Haidong; Qiao, Jian; Fu, Yang-Xin

    2016-01-01

    Recent exciting progress in cancer immunotherapy has ushered in a new era of cancer treatment. Immunotherapy can elicit unprecedented durable responses in advanced cancer patients that are much greater than conventional chemotherapy. However, such responses only occur in a relatively small fraction of patients. A positive response to immunotherapy usually relies on dynamic interactions between tumor cells and immunomodulators inside the tumor microenvironment (TME). Depending on the context of these interactions, the TME may play important roles to either dampen or enhance immune responses. Understanding the interactions between immunotherapy and the TME is not only critical to dissect the mechanisms of action but also important to provide new approaches in improving the efficiency of current immunotherapies. In this review, we will highlight recent work on how the TME can influence the efficacy of immunotherapy as well as how manipulating the TME can improve current immunotherapy regimens in some cases.

  8. Treatment of Bone Tumors

    PubMed Central

    Rajani, Rajiv; Gibbs, C. Parker

    2012-01-01

    Synopsis In this article, the authors summarize the state of the art and future potential in the management of Osteosarcoma, Ewing’s sarcoma, and Chondrosarcoma. They cover systemic therapy, surgical therapy, and radiotherapy, along with targeted therapies to inhibit signal transduction pathways. They discuss staging and the role of imaging evaluation to provide an overview of bone tumor treatment. Images presenting pathologic-radiologic correlations are included. PMID:22328909

  9. Peptide-based method for detection of metastatic transformation in primary tumors of breast cancer.

    PubMed

    Li, Hao; Huang, Yue; Yu, Yue; Li, Weiwei; Yin, Yongmei; Li, Genxi

    2015-09-15

    Detection of metastatic activity before the onset of the actual metastasis can be a promising method to combat metastasis, the foremost cause of death in cancer. Therefore, in this work, we have developed an assay method for the detection of metastatic tumor cells in primary tumor, by using a protein of the metastatic cell signaling as the biomarker. In this assay, a peptide-based probe targeting the marker protein and a sensitive nanoparticle doped graphene nanolabel are combined to enable the detection of metastatic cells. Consequently, the metastatic cells can be specifically detected and discriminated from primary tumor cells. By applying this assay method to clinical samples of primary tumor, a low amount of metastatic activity can be detected in the tumor sites, which may suggest the activity of local metastatic transformation. So, these results may point to the prospect of using the proposed method for controlling metastatic cancer.

  10. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    SciTech Connect

    Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C. ); Grzeschik, K.H. )

    1988-02-01

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration.

  11. [Chemotherapy of brain tumors].

    PubMed

    Kuratsu, J; Ushio, Y

    1994-10-01

    Despite recent attempts to improve chemotherapeutic approaches for the treatment of malignant gliomas, results remain limited and palliative. The development of effective chemotherapy for tumors of the central nervous system (CNS) is complicated in that the blood-brain barrier (B.B.B.) hampers the penetration of most drugs into the brain and cerebrospinal fluid. The factors governing delivery in the brain are the drug's molecular weight, lipophilicity and degree of ionization. Now the standard therapy for malignant glioma is maximal tumor resection followed by combination radiotherapy plus chemotherapy. Nitrosoureas are representative drugs which easily cross the B.B.B.. It has been shown that nitrosourea compounds have an additive effect to radiotherapy. The toxicity profile of nitrosoureas is leukocytopenia and thrombocytopenia as a dose-limiting factor. Furthermore, the great heterogeneity of malignant glioma tissues offered a rationale for the use of multiple drugs. Many studies were reported to show a substantial advantage for the multidrug regimen over control series utilizing single drugs alone. Despite clear examples of the effectiveness of chemotherapy, we are still far from improving the cure rate for the vast majority of patients with primary malignancies of the CNS. Further improvement in patient survival may depend upon understanding and manipulating the pathways that regulate aberrant growth in these tumors. The development of new anticancer agents, which are sensitive to malignant glioma and can reach a high concentration in glioma tissue, is warranted. PMID:7986118

  12. Familial pituitary tumors.

    PubMed

    Alband, Neda; Korbonits, Márta

    2014-01-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern due to hormone overproduction and/or tumor mass effects. The majority of pituitary adenomas occur sporadically; however, familial cases are increasingly being recognized, such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and familial isolated pituitary adenoma (FIPA). Familial pituitary tumors appear to differ from their sporadic counterparts both in their genetic basis and in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, tumors are more aggressive and affect patients at a younger age, therefore justifying the importance of early diagnosis, while in Carney complex pituitary hyperplasia is common. The genetic alterations responsible for the formation of familial pituitary syndromes include the MEN1 gene, responsible for about 80% of MEN1 cases, the regulatory subunit of the protein kinase A, PRKAR1A, responsible for about 70% of Carney complex cases, and AIP, the gene coding the aryl hydrocarbon receptor interacting protein, responsible for about 20% of FIPA cases. Rarely other genes have also been found responsible for familial pituitary adenoma cases. McCune-Albright syndrome (MAS) also has a genetic origin due to mosaic mutations in the G protein-coupled α subunit coded by the GNAS1 gene. In this chapter, we summarize the genetic and clinical characteristics of these familial pituitary syndromes and MAS. PMID:25248598

  13. Radiolabeled Nanoparticles for Multimodality Tumor Imaging

    PubMed Central

    Xing, Yan; Zhao, Jinhua; Conti, Peter S.; Chen, Kai

    2014-01-01

    Each imaging modality has its own unique strengths. Multimodality imaging, taking advantages of strengths from two or more imaging modalities, can provide overall structural, functional, and molecular information, offering the prospect of improved diagnostic and therapeutic monitoring abilities. The devices of molecular imaging with multimodality and multifunction are of great value for cancer diagnosis and treatment, and greatly accelerate the development of radionuclide-based multimodal molecular imaging. Radiolabeled nanoparticles bearing intrinsic properties have gained great interest in multimodality tumor imaging over the past decade. Significant breakthrough has been made toward the development of various radiolabeled nanoparticles, which can be used as novel cancer diagnostic tools in multimodality imaging systems. It is expected that quantitative multimodality imaging with multifunctional radiolabeled nanoparticles will afford accurate and precise assessment of biological signatures in cancer in a real-time manner and thus, pave the path towards personalized cancer medicine. This review addresses advantages and challenges in developing multimodality imaging probes by using different types of nanoparticles, and summarizes the recent advances in the applications of radiolabeled nanoparticles for multimodal imaging of tumor. The key issues involved in the translation of radiolabeled nanoparticles to the clinic are also discussed. PMID:24505237

  14. Noncontact diffuse correlation tomography of human breast tumor

    PubMed Central

    He, Lian; Lin, Yu; Huang, Chong; Irwin, Daniel; Szabunio, Margaret M.; Yu, Guoqiang

    2015-01-01

    Abstract. Our first step to adapt our recently developed noncontact diffuse correlation tomography (ncDCT) system for three-dimensional (3-D) imaging of blood flow distribution in human breast tumors is reported. A commercial 3-D camera was used to obtain breast surface geometry, which was then converted to a solid volume mesh. An ncDCT probe scanned over a region of interest on the mesh surface and the measured boundary data were combined with a finite element framework for 3-D image reconstruction of blood flow distribution. This technique was tested in computer simulations and in vivo human breasts with low-grade carcinoma. Results from computer simulations suggest that relatively high accuracy can be achieved when the entire tumor is within the sensitive region of diffuse light. Image reconstruction with a priori knowledge of the tumor volume and location can significantly improve the accuracy in recovery of tumor blood flow contrasts. In vivo imaging results from two breast carcinomas show higher average blood flow contrasts (5.9- and 10.9-fold) in the tumor regions compared to the surrounding tissues, which are comparable with previous findings using diffuse correlation spectroscopy. The ncDCT system has the potential to image blood flow distributions in soft and vulnerable tissues without distorting tissue hemodynamics. PMID:26259706

  15. Disease-specific target gene expression profiling of molecular imaging probes: database development and clinical validation.

    PubMed

    Chan, Lawrence Wing-Chi; Ngo, Connie Hiu-Ching; Wang, Fengfeng; Zhao, Moss Y; Zhao, Mengying; Law, Helen Ka-Wai; Wong, Sze Chuen Cesar; Yung, Benjamin Yat-Ming

    2014-01-01

    Molecular imaging probes can target abnormal gene expression patterns in patients and allow early diagnosis of disease. For selecting a suitable imaging probe, the current Molecular Imaging and Contrast Agent Database (MICAD) provides descriptive and qualitative information on imaging probe characteristics and properties. However, MICAD does not support linkage with the expression profiles of target genes. The proposed Disease-specific Imaging Probe Profiling (DIPP) database quantitatively archives and presents the gene expression profiles of targets across different diseases, anatomic regions, and subcellular locations, providing an objective reference for selecting imaging probes. The DIPP database was validated with a clinical positron emission tomography (PET) study on lung cancer and an in vitro study on neuroendocrine cancer. The retrieved records show that choline kinase beta and glucose transporters were positively and significantly associated with lung cancer among the targets of 11C-choline and [18F]fluoro-2-deoxy-2-d-glucose (FDG), respectively. Their significant overexpressions corresponded to the findings that the uptake rate of FDG increased with tumor size but that of 11C-choline remained constant. Validated with the in vitro study, the expression profiles of disease-associated targets can indicate the eligibility of patients for clinical trials of the treatment probe. A Web search tool of the DIPP database is available at http://www.polyu.edu.hk/bmi/dipp/. PMID:25022454

  16. Rapid and sensitive detection of early esophageal squamous cell carcinoma with fluorescence probe targeting dipeptidylpeptidase IV

    PubMed Central

    Onoyama, Haruna; Kamiya, Mako; Kuriki, Yugo; Komatsu, Toru; Abe, Hiroyuki; Tsuji, Yosuke; Yagi, Koichi; Yamagata, Yukinori; Aikou, Susumu; Nishida, Masato; Mori, Kazuhiko; Yamashita, Hiroharu; Fujishiro, Mitsuhiro; Nomura, Sachiyo; Shimizu, Nobuyuki; Fukayama, Masashi; Koike, Kazuhiko; Urano, Yasuteru; Seto, Yasuyuki

    2016-01-01

    Early detection of esophageal squamous cell carcinoma (ESCC) is an important prognosticator, but is difficult to achieve by conventional endoscopy. Conventional lugol chromoendoscopy and equipment-based image-enhanced endoscopy, such as narrow-band imaging (NBI), have various practical limitations. Since fluorescence-based visualization is considered a promising approach, we aimed to develop an activatable fluorescence probe to visualize ESCCs. First, based on the fact that various aminopeptidase activities are elevated in cancer, we screened freshly resected specimens from patients with a series of aminopeptidase-activatable fluorescence probes. The results indicated that dipeptidylpeptidase IV (DPP-IV) is specifically activated in ESCCs, and would be a suitable molecular target for detection of esophageal cancer. Therefore, we designed, synthesized and characterized a series of DPP-IV-activatable fluorescence probes. When the selected probe was topically sprayed onto endoscopic submucosal dissection (ESD) or surgical specimens, tumors were visualized within 5 min, and when the probe was sprayed on biopsy samples, the sensitivity, specificity and accuracy reached 96.9%, 85.7% and 90.5%. We believe that DPP-IV-targeted activatable fluorescence probes are practically translatable as convenient tools for clinical application to enable rapid and accurate diagnosis of early esophageal cancer during endoscopic or surgical procedures. PMID:27245876

  17. Testis tumor associated to microlithiasis

    PubMed Central

    de Jesus, Lisieux Eyer; Maciel, Felipe; Monnerat, Andrea Lima C.; Fernandes, Marcia Antunes; Dekermache, Samuel

    2013-01-01

    OBJECTIVE: To discuss the relationship between testicular microlithiasis and testis tumors in children and to consider the chances of testis preserving surgery in specific cases. CASE DESCRIPTION: Pre-adolescent presenting testicular microlithiasis and a larger left testis, corresponding to a cystic testicular tumor. The tumor was excised, with ipsilateral testis preservation. Histology diagnosed a testis dermoid tumor. COMMENTS: The relationship between testis tumors and testicular microlithiasis is ill defined in children. Pediatric urologists need to develop specific follow-up protocols for pre-pubertal children. PMID:24473964

  18. Mucoepidermoid tumors of the lung.

    PubMed

    Yousem, S A; Hochholzer, L

    1987-09-15

    Mucoepidermoid tumors of lung (MET) are rare tumors derived from the minor salivary gland tissue of the proximal tracheobronchial tree. The authors studied 58 cases of MET confined to the lung and used criteria derived from similar tumors of the salivary glands to separate them into low-grade and high-grade variants. The overwhelming majority of low-grade tumors behaved in a benign fashion, whereas 23% of high-grade tumors resulted in patient death. Prognostic factors which appeared to predict future aggressive behavior included high-grade classification, advanced stage at presentation, and perhaps lymph node metastases.

  19. Signs and Symptoms of Wilms Tumor

    MedlinePlus

    ... early? Next Topic How are Wilms tumors diagnosed? Signs and symptoms of Wilms tumor Wilms tumors can ... the abdomen (belly): This is often the first sign of a Wilms tumor. Parents may notice this ...

  20. Can Gastrointestinal Carcinoid Tumors Be Found Early?

    MedlinePlus

    ... problems. Carcinoid tumors often are found incidentally (by accident). These tumors aren’t causing any symptoms but ... Carcinoid Tumors? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treating Gastrointestinal Carcinoid Tumors Talking ...

  1. SPECT/NIRF Dual Modality Imaging for Detection of Intraperitoneal Colon Tumor with an Avidin/Biotin Pretargeting System

    PubMed Central

    Dong, Chengyan; Yang, Sujuan; Shi, Jiyun; Zhao, Huiyun; Zhong, Lijun; Liu, Zhaofei; Jia, Bing; Wang, Fan

    2016-01-01

    We describe herein dual-modality imaging of intraperitoneal colon tumor using an avidin/biotin pretargeting system. A novel dual-modality probe, 99mTc-HYNIC-lys(Cy5.5)-PEG4-biotin, was designed, synthesized and characterized. Single-photon emission computed tomography/ computed tomography (SPECT/CT) imaging and near infrared fluorescence (NIRF) imaging were developed using intraperitoneal LS180 human colon adenocarcinoma xenografts. Following avidin preinjection for 4 hours, 99mTc-HYNIC-lys(Cy5.5)-PEG4-biotin could successfully detect colon tumors of different sizes inside the abdominal region using both modalities, and the imaging results showed no differences. Biodistribution studies demonstrated that the tumors had a very high uptake of the probe 99mTc-HYNIC-lys(Cy5.5)-PEG4-biotin (12.74 ± 1.89% ID/g at 2 h p.i.), and the clearance from blood and other normal tissues occured very fast. The low tumor uptake in the non-pretargeted mice (1.63 ± 0.50% ID/g at 2 h p.i.) and tumor cell staining results showed excellent tumor binding specificity of the pretargeting system. The ability of the novel probe to show excellent imaging quality with high tumor-to-background contrast, a high degree of binding specificity with tumors and excellent in vivo biodistribution pharmacokinetics should prove that the avidin/biotin based dual-modality pretargeting probe is a promising imaging tool during the entire period of tumor diagnosis and treatment. PMID:26732543

  2. Plasmonic nanohalo optical probes for highly sensitive imaging of survivin mRNA in living cells.

    PubMed

    Qian, Guang-Sheng; Kang, Bin; Zhang, Zhuo-Lei; Li, Xiang-Ling; Zhao, Wei; Xu, Jing-Juan; Chen, Hong-Yuan

    2016-09-25

    A strategy is designed for sensitive detection of tumor biomarker survivin mRNA based on resonance Rayleigh scattering of a single AuNP nanohalo probe that couples large gold nanoparticles (L-AuNPs, 52 nm) with small AuNPs (S-AuNPs, 18 nm) through the affinity interaction between streptavidin and biotin. This core-satellite plasmon ruler is further applied to imaging survivin mRNA in living cells. PMID:27412908

  3. Plasmonic nanohalo optical probes for highly sensitive imaging of survivin mRNA in living cells.

    PubMed

    Qian, Guang-Sheng; Kang, Bin; Zhang, Zhuo-Lei; Li, Xiang-Ling; Zhao, Wei; Xu, Jing-Juan; Chen, Hong-Yuan

    2016-09-25

    A strategy is designed for sensitive detection of tumor biomarker survivin mRNA based on resonance Rayleigh scattering of a single AuNP nanohalo probe that couples large gold nanoparticles (L-AuNPs, 52 nm) with small AuNPs (S-AuNPs, 18 nm) through the affinity interaction between streptavidin and biotin. This core-satellite plasmon ruler is further applied to imaging survivin mRNA in living cells.

  4. Development of 99mTc-N4-NIM for Molecular Imaging of Tumor Hypoxia

    PubMed Central

    Ali, Mohammad S.; Kong, Fan-Lin; Rollo, Alex; Mendez, Richard; Kohanim, Saady; Smith, Daniel Lee; Yang, David J.

    2012-01-01

    The nitro group of 2-nitroimidazole (NIM) enters the tumor cells and is bioreductively activated and fixed in the hypoxia cells. 1,4,8,11-tetraazacyclotetradecane (N4) has shown to be a stable chelator for 99mTc. The present study was aimed to develop 99mTc-cyclam-2-nitroimidazole (99mTc-N4-NIM) for tumor hypoxia imaging. N4-NIM precursor was synthesized by reacting N4-oxalate and 1,3-dibromopropane-NIM, yielded 14% (total synthesis). Cell uptake of 99mTc-N4-NIM and 99mTc-N4 was obtained in 13762 rat mammary tumor cells and mesothelioma cells in 6-well plates. Tissue distribution of 99mTc-N4-NIM was evaluated in breast-tumor-bearing rats at 0.5–4 hrs. Tumor oxygen tension was measured using an oxygen probe. Planar imaging was performed in the tumor-bearing rat and rabbit models. Radiochemical purity of 99mTc-N4-NIM was >96% by HPLC. Cell uptake of 99mTc-N4-NIM was higher than 99mTc-N4 in both cell lines. Biodistribution of 99mTc-N4-NIM showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time. Oxygen tension in tumor tissue was 6–10 mmHg compared to 40–50 mmHg in normal muscle tissue. Planar imaging studies confirmed that the tumors could be visualized clearly with 99mTc-N4-NIM in animal models. Efficient synthesis of N4-NIM was achieved. 99mTc-N4-NIM is a novel hypoxic probe and may be useful in evaluating cancer therapy. PMID:22719210

  5. Laser therapy in intraocular tumors

    NASA Astrophysics Data System (ADS)

    Carstocea, Benone D.; Gafencu, Otilia L.; Apostol, Silvia

    1995-01-01

    Intraocular tumors present special problems of diagnosis and treatment. Diagnostic methods include, in addition to systemic and ophthalmological examinations, ancillary examinations such as transillumination, fluorescein angiography, ultrasonography, radioactive phosphorus uptake test, radiology, computerized tomography, and fine-needle aspiration biopsy with cytological analyses. Previously, enucleation of the involved eye was generally accepted as management of malignant tumors. Improved therapeutic methods such as photocoagulation and better surgical techniques now provide a variety of therapeutical alternatives. This study consists of 21 cases of intraocular tumors that were managed by Argon laser photocoagulation. Four cases were intraocular metastasis and 17 cases were primitive intraocular tumors. Argon laser therapy proved to be totally ineffective for the intraocular metastasis and a very adequate therapy for the primitive tumors. Tumor extirpations (choroidal, cillary body, or iris tumors) using laser lancet proved to be more suitable than classic surgery.

  6. [Tumors of the parotid gland].

    PubMed

    Tresserra, L; Tresserra, F

    1997-09-01

    Tumors of the parotid are the most frequently encountered salivary gland tumors. Knowledge of the histology and anatomy of the salivary gland is important when considering the histiogenesis of salivary gland tumors, requiring close cooperation between the pathologist and the surgeon. Most tumors are benign epithelial formations. Pleomorphous adenomas predominate. Superficial lobectomy is adequate treatment. When the tumor involves a deep lobe, total parotidectomy is indicated. Treatment of malignant tumors depends on the histology, its TNM stage and other factors. Total parotidectomy with lymphadectomy and radiotherapy are needed in case of high grade malignancy. In children, vascular neoplasias are the most frequent, followed by malignant tumors. Their histological features and treatment are the same as for adults.

  7. Collecting Tumor Samples From Patients With Gynecological Tumors

    ClinicalTrials.gov

    2016-10-26

    Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell

  8. Probing the nano-bio interface with nanoplasmonic optical probes

    NASA Astrophysics Data System (ADS)

    Yu, X.; Wu, Linxi; Khanehzar, Ali; Feizpour, Amin; Xu, Fangda; Reinhard, Björn M.

    2014-08-01

    Noble metal nanoparticles have large cross-sections in both optical and electron microscopy and plasmon coupling between noble metal nanoparticles facilitate the characterization of subdiffraction limit separations through spectral analysis of the scattered light in Plasmon Coupling Microscopy (PCM). The size compatibility of noble metal nanoparticles together with the ability to encode specific functionality in a rational fashion by control of the nanoparticle surface makes noble metal nanoparticles unique probes for a broad range of biological processes. Recent applications of the technology include i.) characterization of cellular heterogeneity in nanomaterial uptake and processing through macrophages, ii.) testing the role of viral membrane lipids in mediating viral binding and trafficking, and iii.) characterizing the spatial organization of cancer biomarkers in plasma membranes. This paper reviews some of these applications and introduces the physical and material science principles underlying them. We will also introduce the use of membrane wrapped noble metal nanoparticles, which combine the superb photophysical properties of a nanoparticle core with the biological functionality of a membrane, as probes in PCM.

  9. Tumor size: effect on monoclonal antibody uptake in tumor models

    SciTech Connect

    Hagan, P.L.; Halpern, S.E.; Dillman, R.O.; Shawler, D.L.; Johnson, D.E.; Chen, A.; Krishnan, L.; Frincke, J.; Bartholomew, R.M.; David, G.S.

    1986-03-01

    Studies were performed to determine the effect of tumor size on the incorporation of radiolabeled monoclonal antitumor antibodies (MoAbs) into human tumors growing in nude mice. The colon tumors ranged in size from 0.03-1.6 g, the melanoma from 0.1 to 6.7 g, and the lymphoma from 0.06 to 10.2 g. Indium-111 was primarily used as the radiolabel, however, both 125I and 111In were used as tracers for the MoAb in one experiment. The per g radiopharmaceutical uptake by tumors was inversely proportional to tumor size when tumor specific MoAb was administered. This finding was independent of the radiolabel and was demonstrable when the mice bore two tumors of differing size. When the MoAb was not specific for the tumor, the data were less well defined and a statistically significant correlation with size did not occur. These data are strong evidence for a decrease in per g uptake of labeled tumor specific antibodies as tumors increase in size.

  10. Intracellular particle tracking as a tool for tumor cell characterization

    NASA Astrophysics Data System (ADS)

    Li, Yixuan; Schnekenburger, Juergen; Duits, Michael H. G.

    2009-11-01

    We studied the dynamics of two types of intracellular probe particles, ballistically injected latex spheres and endogenous granules, in tumor cell lines of differerent metastatic potential: breast tumor cells (MCF-7 malignant, MCF-10A benign) and pancreas adenocarcinoma (PaTu8988T malignant, PaTu8988S benign). For both tissue types and for both probes, the mean squared displacement (MSD) function measured in the malignant cells was substantially larger than in the benign cells. Only a few cells were needed to characterize the tissue as malignant or benign based on their MSD, since variations in MSD within the same cell line were relatively small. These findings suggest that intracellular particle tracking (IPT) can serve as a simple and reliable method for characterization of cell states obtained from a small amount of cell sample. Mechanical analysis of the same cell lines with atomic force microscopy (AFM) in force-distance mode revealed that AFM could distinguish between the benign and malignant breast cancer cells but not the pancreatic tumor cell lines. This underlines the potential value of IPT as a complementary nanomechanical tool for studying cell-state-dependent mechanical properties.

  11. Solar probe: an engineering solution

    NASA Astrophysics Data System (ADS)

    Bedini, P.; Potocki, K.

    2003-04-01

    Solar Probe, a program to study the origins of the solar wind and the heating of the Sun's corona, is currently a mission under study in NASA's Sun-Earth Connection Theme. The availability of the Evolved Expendable Launch Vehicle (EELV) and Multi-Mission Radioisotope Thermoelectric Generators has enabled the development of an implementable Solar Probe mission concept that now offers substantial resources (55 kg and 47 W) for its science payload. The mission design assumes a launch on an EELV and uses a direct Jupiter Gravity Assist to reach a perihelion of 4 RS. The mission affords two polar solar passes with Earth in quadrature within 7.1 years from launch. A large (2.7-m diameter x 5.1-m), conical Carbon-Carbon thermal protection system harbors a complement of in situ and remote-sensing instruments (based on the 1999 Solar Probe Science Definition Team straw-man payload). A Ka-band telecommunications system allows uninterrupted real-time data downlink at perihelion (p) despite coronal scintillation effects, providing > 25 kbps even at closest approach. The 43.2 Gbits of data down-linked during each pass (p - 10 days through p + 10 days) is augmented by as much as another 128 Gbits of data recorded on redundant solid-state recorders for post-perihelion playback. The capability exists to download cruise mode science as well. Fault tolerance is achieved using redundant avionics and a dedicated attitude control unit to assure that the proper orientation of the spacecraft is maintained throughout the passes. Viable opportunities begin with a 2010 launch, provided new start authority is obtained in FY-05.

  12. Solar probe: an engineering study

    NASA Astrophysics Data System (ADS)

    Bedini, P.; Potocki, K.

    2003-04-01

    Solar Probe, a program to study the origins of the solar wind and the heating of the Sun’s corona, is currently a mission under study in NASA’s Sun-Earth Connection Theme. The availability of the Evolved Expendable Launch Vehicle (EELV) and Multi-Mission Radioisotope Thermoelectric Generators has enabled the development of an implementable Solar Probe mission concept that now offers substantial resources (55 kg and 47 W) for its science payload. The mission design assumes a launch on an EELV and uses a direct Jupiter Gravity Assist to reach a perihelion of 4 RS. The mission affords two polar solar passes with Earth in quadrature within 7.1 years from launch. A large (2.7-m diameter × 5.1-m), conical Carbon-Carbon thermal protection system harbors a complement of in situ and remote-sensing instruments (based on the 1999 Solar Probe Science Definition Team straw-man payload). A Ka-band telecommunications system allows uninterrupted real-time data downlink at perihelion (p) despite coronal scintillation effects, providing > 25 kbps even at closest approach. The 43.2 Gbits of data down-linked during each pass (p -- 10 days through p + 10 days) is augmented by as much as another 128 Gbits of data recorded on redundant solid-state recorders for post-perihelion playback. The capability exists to download cruise mode science as well. Fault tolerance is achieved using redundant avionics and a dedicated attitude control unit to assure that the proper orientation of the spacecraft is maintained throughout the passes. Viable opportunities begin with a 2010 launch, provided new start authority is obtained in FY-05.

  13. Wnt5a Suppresses Tumor Formation and Redirects Tumor Phenotype in MMTV-Wnt1 Tumors

    PubMed Central

    Easter, Stephanie L.; Mitchell, Elizabeth H.; Baxley, Sarah E.; Desmond, Renee; Frost, Andra R.; Serra, Rosa

    2014-01-01

    Wnt5a is a non-canonical signaling Wnt that has been implicated in tumor suppression. We previously showed that loss of Wnt5a in MMTV-PyVmT tumors resulted in a switch in tumor phenotype resulting in tumors with increased basal phenotype and high Wnt/β-catenin signaling. The object of this study was to test the hypothesis that Wnt5a can act to inhibit tumors formed by activation of Wnt/β-catenin signaling. To this end, we characterized tumor and non-tumor mammary tissue from MMTV-Wnt1 and double transgenic MMTV-Wnt1;MMTV-Wnt5a mice. Wnt5a containing mice demonstrated fewer tumors with increased latency when compared to MMTV-Wnt1 controls. Expression of markers for basal-like tumors was down-regulated in the tumors that formed in the presence of Wnt5a indicating a phenotypic switch. Reduced canonical Wnt signaling was detected in double transgenic tumors as a decrease in active β-catenin protein and a decrease in Axin2 mRNA transcript levels. In non-tumor tissues, over-expression of Wnt5a in MMTV-Wnt1 mammary glands resulted in attenuation of phenotypes normally observed in MMTV-Wnt1 glands including hyperbranching and increased progenitor and basal cell populations. Even though Wnt5a could antagonize Wnt/β-catenin signaling in primary mammary epithelial cells in culture, reduced Wnt/β-catenin signaling was not detected in non-tumor MMTV-Wnt1;Wnt5a tissue in vivo. The data demonstrate that Wnt5a suppresses tumor formation and promotes a phenotypic shift in MMTV-Wnt1 tumors. PMID:25401739

  14. Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors.

    PubMed

    Easter, Stephanie L; Mitchell, Elizabeth H; Baxley, Sarah E; Desmond, Renee; Frost, Andra R; Serra, Rosa

    2014-01-01

    Wnt5a is a non-canonical signaling Wnt that has been implicated in tumor suppression. We previously showed that loss of Wnt5a in MMTV-PyVmT tumors resulted in a switch in tumor phenotype resulting in tumors with increased basal phenotype and high Wnt/β-catenin signaling. The object of this study was to test the hypothesis that Wnt5a can act to inhibit tumors formed by activation of Wnt/β-catenin signaling. To this end, we characterized tumor and non-tumor mammary tissue from MMTV-Wnt1 and double transgenic MMTV-Wnt1;MMTV-Wnt5a mice. Wnt5a containing mice demonstrated fewer tumors with increased latency when compared to MMTV-Wnt1 controls. Expression of markers for basal-like tumors was down-regulated in the tumors that formed in the presence of Wnt5a indicating a phenotypic switch. Reduced canonical Wnt signaling was detected in double transgenic tumors as a decrease in active β-catenin protein and a decrease in Axin2 mRNA transcript levels. In non-tumor tissues, over-expression of Wnt5a in MMTV-Wnt1 mammary glands resulted in attenuation of phenotypes normally observed in MMTV-Wnt1 glands including hyperbranching and increased progenitor and basal cell populations. Even though Wnt5a could antagonize Wnt/β-catenin signaling in primary mammary epithelial cells in culture, reduced Wnt/β-catenin signaling was not detected in non-tumor MMTV-Wnt1;Wnt5a tissue in vivo. The data demonstrate that Wnt5a suppresses tumor formation and promotes a phenotypic shift in MMTV-Wnt1 tumors.

  15. Modeling an optical micromachine probe

    SciTech Connect

    Mittas, A.; Dickey, F.M.; Holswade, S.C.

    1997-08-01

    Silicon micromachines are fabricated using Surface Micro-Machining (SMM) techniques. Silicon micromachines include engines that consist of orthogonally oriented linear comb drive actuators mechanically connected to a rotating gear. These gears are as small a 50-{micro}m in diameter and can be driven at rotation rates exceeding 300,000-rpm. Measuring and analyzing microengine performance is basic to micromachine development and system applications. Optical techniques offer the potential for measuring long term statistical performance data and transient responses needed to optimize designs and manufacturing techniques. The authors describe the modeling of an optical probe developed at Sandia National Laboratories. Experimental data will be compared with output from the model.

  16. Multifunctional Gold Nanostar Conjugates for Tumor Imaging and Combined Photothermal and Chemo-therapy

    PubMed Central

    Chen, Haiyan; Zhang, Xin; Dai, Shuhang; Ma, Yuxiang; Cui, Sisi; Achilefu, Samuel; Gu, Yueqing

    2013-01-01

    Uniform gold nanostars (Au NS) were conjugated with cyclic RGD (cRGD) and near infrared (NIR) fluorescence probe (MPA) or anti-cancer drug (DOX) to obtain multi-functional nanoconstructs, Au-cRGD-MPA and Au-cRGD-DOX respectively. The NIR contrast agent Au-cRGD-MPA was shown to have low cytotoxicity. Using tumor cells and tumor bearing mice, these imaging nanoparticles demonstrated favorable tumor-targeting capability mediated by RGD peptide binding to its over-expressed receptor on the tumor cells. The multi-therapeutic analogue, Au-cRGD-DOX, integrates targeting tumor, chemotherapy and photo-thermotherapy into a single system. The synergistic effect of photo-thermal therapy and chemotherapy was demonstrated in different tumor cell lines and in vivo using S180 tumor-bearing mouse models. The viability of MDA-MB-231 cells was only 40 % after incubation with Au-cRGD-DOX and irradiation with NIR light. Both tail vein and intratumoral injections showed Au-cRGD-DOX treated mice exhibiting the slowest tumor increase. These results indicate that the multifunctional nanoconstruct is a promising combined therapeutic agent for tumor-targeting treatment, with the potential to enhance the anti-cancer treatment outcomes. PMID:24019851

  17. Study of Kidney Tumors in Younger Patients

    ClinicalTrials.gov

    2016-05-17

    Clear Cell Sarcoma of the Kidney; Congenital Mesoblastic Nephroma; Diffuse Hyperplastic Perilobar Nephroblastomatosis; Rhabdoid Tumor of the Kidney; Stage I Renal Cell Cancer; Stage I Wilms Tumor; Stage II Renal Cell Cancer; Stage II Wilms Tumor; Stage III Renal Cell Cancer; Stage III Wilms Tumor; Stage IV Renal Cell Cancer; Stage IV Wilms Tumor; Stage V Wilms Tumor

  18. Mathematical study of probe arrangement and nanoparticle injection effects on heat transfer during cryosurgery.

    PubMed

    Mirkhalili, Seyyed Mostafa; Ramazani S A, Ahmad; Nazemidashtarjandi, Saeed

    2015-11-01

    Blood vessels, especially large vessels have a greater thermal effect on freezing tissue during cryosurgery. Vascular networks act as heat sources in tissue, and cause failure in cryosurgery and reappearance of cancer. The aim of this study is to numerically simulate the effect of probe location and multiprobe on heat transfer distribution. Furthermore, the effect of nanoparticles injection is studied. It is shown that the small probes location near large blood vessels could help to reduce the necessary time for tissue freezing. Nanoparticles injection shows that the thermal effect of blood vessel in tissue is improved. Using Au, Ag and diamond nanoparticles have the most growth of ice ball during cryosurgery. However, polytetrafluoroethylene (PTFE) nanoparticle can be used to protect normal tissue around tumor cell due to its influence on reducing heat transfer in tissue. Introduction of Au, Ag and diamond nanoparticles combined with multicryoprobe in this model causes reduction of tissue average temperature about 50% compared to the one probe. PMID:26406880

  19. Mathematical study of probe arrangement and nanoparticle injection effects on heat transfer during cryosurgery.

    PubMed

    Mirkhalili, Seyyed Mostafa; Ramazani S A, Ahmad; Nazemidashtarjandi, Saeed

    2015-11-01

    Blood vessels, especially large vessels have a greater thermal effect on freezing tissue during cryosurgery. Vascular networks act as heat sources in tissue, and cause failure in cryosurgery and reappearance of cancer. The aim of this study is to numerically simulate the effect of probe location and multiprobe on heat transfer distribution. Furthermore, the effect of nanoparticles injection is studied. It is shown that the small probes location near large blood vessels could help to reduce the necessary time for tissue freezing. Nanoparticles injection shows that the thermal effect of blood vessel in tissue is improved. Using Au, Ag and diamond nanoparticles have the most growth of ice ball during cryosurgery. However, polytetrafluoroethylene (PTFE) nanoparticle can be used to protect normal tissue around tumor cell due to its influence on reducing heat transfer in tissue. Introduction of Au, Ag and diamond nanoparticles combined with multicryoprobe in this model causes reduction of tissue average temperature about 50% compared to the one probe.

  20. A Microfluidic Microbeads Fluorescence Assay with Quantum Dots-Bead-DNA Probe.

    PubMed

    Ankireddy, S R; Kim, Jongsung

    2016-03-01

    A microfluidic bead-based nucleic acid sensor for the detection of tumor causing N-Ras genes using quantum dots has been developed. Presently, quantum dots-bead-DNA probe based hybridization detection methods are often called as 'bead based assays' and their success is substantially influenced by the dispensing and manipulation capability of the microfluidic technology. This study reports the detection of N-Ras cancer gene by fluorescence quenching of quantum dots immobilized on the surface of polystyrene beads. A microfluidic chip was constructed in which the quantum dots-bead-DNA probes were packed in the channel. The target DNA flowed across the beads and hybridized with immobilized probe sequences. The target DNA can be detected by the fluorescence quenching of the quantum dots due to their transfer of emission energy to intercalation dye after DNA hybridization. The mutated gene also induces fluorescence quenching but with less degree than the perfectly complementary target DNA.