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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. Probing Tumor Microenvironment with In Vivo Phage Display

    DTIC Science & Technology

    2013-07-01

    peptides may result in an efficient probe for breast tumor imaging and therapy . 15. SUBJECT TERMS Carcinoma-associated fibroblast; phage display...In Vivo Phage Display PRINCIPAL INVESTIGATOR: Dr. Erkki Ruoslahti CONTRACTING ORGANIZATION: Sanford Burnham Medical Research Institute...COVERED 01 July 2012 – 30 June 2013 4. TITLE AND SUBTITLE Probing Tumor Microenvironment with In Vivo Phage Display 5a. CONTRACT NUMBER W81XWH

  4. Probing the tumor microenvironment: collection and induction

    NASA Astrophysics Data System (ADS)

    Williams, James K.; Padgen, Michael R.; Wang, Yarong; Entenberg, David; Gertler, Frank; Condeelis, John S.; Castracane, James

    2012-03-01

    The Nano Intravital Device, or NANIVID, is under development as an optically transparent, implantable tool to study the tumor microenvironment. Two etched glass substrates are sealed using a thin polymer membrane to create a reservoir with a single outlet. This reservoir is loaded with a hydrogel blend that contains growth factors or other chemicals to be delivered to the tumor microenvironment. When the device is implanted in the tumor, the hydrogel will swell and release these entrapped molecules, forming a gradient. Validation of the device has been performed in vitro using epidermal growth factor (EGF) and MenaINV, a highly invasive, rat mammary adenocarcinoma cell line. In both 2-D and 3-D environments, cells migrated toward the gradient of EGF released from the device. The chorioallantoic membrane (CAM) of White Leghorn chicken eggs is being utilized to grow xenograft tumors that will be used for ex vivo cell collection. Device optimization is being performed for in vivo use as a tool to collect the invasive cell population. Preliminary cell collection experiments in vivo were performed using a mouse model of breast cancer. As a second application, the device is being explored as a delivery vehicle for chemicals that induce controlled changes in the tumor microenvironment. H2O2 was loaded in the device and generated intracellular reactive oxygen species (ROS) in cells near the device outlet. In the future, other induction targets will be explored, including hypoglycemia and the manipulation of extracellular matrix stiffness.

  5. Recent advances in activatable fluorescence imaging probes for tumor imaging.

    PubMed

    Zhao, Jing; Jin, Guorui; Weng, Guojun; Li, Jianjun; Zhu, Jian; Zhao, Junwu

    2017-04-20

    Fluorescence imaging is superior in sensitivity and resolution compared with other imaging modalities; however, its application is hindered by high background noise. Tissue-selective strategies, such as passive, active, and activatable targeting, hold great promise in accelerating clinical translation by significantly improving the tumor:background ratio (TBR) and, in turn, the sensitivity and contrast of fluorescence imaging. Compared with the 'always on' contrast agents, activatable probes, which remain nonfluorescent until being activated by tumor-specific molecular targets, further enhance TBR and at the same time provide additional molecular information that can be related to tumor staging and therapy response. In this review, we summarize recent advances in the development of activatable fluorescence probes and provide insights into their advantages and limitations when used for tumor imaging. Copyright © 2017. Published by Elsevier Ltd.

  6. Self-assembled peptide nanoparticles as tumor microenvironment activatable probes for tumor targeting and imaging.

    PubMed

    Zhao, Ying; Ji, Tianjiao; Wang, Hai; Li, Suping; Zhao, Yuliang; Nie, Guangjun

    2014-03-10

    Design of specific and sensitive imaging probes for targeting tumor microenvironment holds great promise to achieve precise detection and rapid responsiveness to neoplastic tissues. Dysregulated pH, one of the most remarkable hallmarks of tumor microenvironment, can be considered as a good specific trigger for the design of broad-spectrum and local-environment responsive imaging probes. However, the current existing design strategies for pH-responsive systems are insufficient to meet the needs for a rapid and tumor-specific diagnosis. Here we reported a novel biomimetic nanostructure based on oligopeptide self-assembly that can quickly switch into dissociated stage with active fluorescence property from self-assembled stage with quenched fluorescence activity when encountering a subtle pH-change in tumor microenvironment (pH 6.8 vs. 7.4). This oligopeptide-assembly is examined as tumor microenvironment activatable probes for both intratumoral and intravenous in vivo tumor imaging. Through the distinct fluorescent intensities, it is validated that the acidic tumor microenvironment can activate stronger fluorescence signals. The tailor-made self-assembled oligopeptide nanomaterials have the potential for efficient and specific in situ diagnosis of various solid tumors with a weakly acidic microenvironment, which is expected to be of crucial importance for clinical tumor diagnostics. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. An enzymatically activated fluorescence probe for targeted tumor imaging

    PubMed Central

    Kamiya, Mako; Kobayashi, Hisataka; Hama, Yukihiro; Koyama, Yoshinori; Bernardo, Marcelino; Nagano, Tetsuo; Choyke, Peter L.; Urano, Yasuteru

    2008-01-01

    β-Galactosidase is a widely used reporter enzyme, but although several substrates are available for in vitro detection, its application for in vivo optical imaging remains a challenge. To obtain a probe suitable for in vivo use, we modified our previously developed activatable fluorescence probe, TG-βGal (J. Am. Chem. Soc., 2005, 127, 4888-4894), on the basis of photochemical and photophysical experiments. The new probe, AM-TG-βGal, provides a dramatic fluorescence enhancement upon reaction with β-galactosidase, and further hydrolysis of the ester moiety by ubiquitous intracellular esterases affords a hydrophilic product that is well retained within the cells without loss of fluorescence. We used a mouse tumor model to assess the practical utility of AM-TG-βGal, after confirming that tumors in the model could be labeled with avidin-β-galactosidase conjugate. This conjugate was administered to the mice in vivo, followed by AM-TG-βGal, and subsequent ex vivo fluorescence imaging clearly visualized intraperitoneal tumors as small as 200 μm. This strategy has potential clinical application, for example in video-assisted laparoscopic tumor resection. PMID:17352471

  8. Probing Tumor Microenvironment with in Vivo Phage Display

    DTIC Science & Technology

    2013-07-01

    Vivo Phage Display PRINCIPAL INVESTIGATOR: Kazuki N. Sugahara, M.D., Ph.D...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Probing Tumor Microenvironment with In Vivo Phage Display 5b. GRANT NUMBER W81XWH-12-1-0174 5c...cells and the matrix. The goal of our group is to make technical improvements in our phage display system, and find peptides that target carcinoma

  9. In silico properties characterization of water-soluble γ-cyclodextrin bi-capped C60 complex: free energy and geometrical insights for stability and solubility.

    PubMed

    Cao, Ruyin; Wu, Shanshan

    2015-06-25

    Cyclodextrin-related host-guest encapsulation is pivotal to modulate the solubility of C60, thereby promoting its potential therapeutic applications. Here we present a computational study on γ-cyclodextrin bi-capped C60 complex, probing characteristics for all the possible stoichiometry in aqueous solution. The potential of mean force (PMF) delineating the association process was computed, while the geometrical features of corresponding thermodynamically-favored stoichiometry are captured by molecular dynamics simulations, which provides insightful explanations to previous experimental and computational results. PMF partitioning indicates that intermolecular van der Waals dispersion forces are essential for molecular recognition and self-assembly, and the hydrogen-bonding interactions play a key role in dissolving the complex in water. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Topical Application of Activity-based Probes for Visualization of Brain Tumor Tissue

    PubMed Central

    Cutter, Jennifer L.; Cohen, Nathan T.; Wang, Jing; Sloan, Andrew E.; Cohen, Alan R.; Panneerselvam, Ashok; Schluchter, Mark; Blum, Galia; Bogyo, Matthew; Basilion, James P.

    2012-01-01

    Several investigators have shown the utility of systemically delivered optical imaging probes to image tumors in small animal models of cancer. Here we demonstrate an innovative method for imaging tumors and tumor margins during surgery. Specifically, we show that optical imaging probes topically applied to tumors and surrounding normal tissue rapidly differentiate between tissues. In contrast to systemic delivery of optical imaging probes which label tumors uniformly over time, topical probe application results in rapid and robust probe activation that is detectable as early as 5 minutes following application. Importantly, labeling is primarily associated with peri-tumor spaces. This methodology provides a means for rapid visualization of tumor and potentially infiltrating tumor cells and has potential applications for directed surgical excision of tumor tissues. Furthermore, this technology could find use in surgical resections for any tumors having differential regulation of cysteine cathepsin activity. PMID:22427947

  11. 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

  12. Polymeric (1) H MRI Probes for Visualizing Tumor In Vivo.

    PubMed

    Kondo, Teruyuki; Kimura, Yu; Yamada, Hisatsugu; Aoyama, Yasuhiro

    2017-04-07

    Magnetic resonance imaging (MRI) has become a prominent non- or low-invasive imaging technique, providing high-resolution, three-dimensional images as well as physiological information about tissues. Low-molecular-weight Gd-MRI contrast agents (CAs), such as Gd-DTPA (DTPA: diethylenetriaminepentaacetic acid), are commonly used in the clinical diagnosis, while macromolecular Gd-MRI CAs have several advantages over low-molecular-weight Gd-MRI CAs, which help minimize the dose of CAs and the risk of side effects. Accordingly, we developed chiral dendrimer Gd-MRI CAs, which showed high r1 values. The association constant values (Ka ) of S-isomeric dendrimer CAs to bovine serum albumin (BSA) were higher than those of R-isomeric dendrimer CAs. Besides, based on a totally new concept, we developed (13) C/(15) N-enriched multiple-resonance NMR/MRI probes, which realized highly selective observation of the probes and analysis of metabolic reactions of interest. This account summarizes our recent study on developing both chiral dendrimer Gd-MRI CAs, and self-traceable (13) C/(15) N-enriched phosphorylcholine polymer probes for early detection of tumors.

  13. Probing model tumor interfacial properties using piezoelectric cantilevers

    NASA Astrophysics Data System (ADS)

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

    2010-09-01

    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.

  14. [Targeted magnetic nanoparticles used as probe for magnetic resonance molecular imaging of tumor].

    PubMed

    Lu, Jing-Jing; Wang, Fang; Jin, Zheng-Yu; Zhong, Ding-Rong

    2009-04-01

    To investigate the feasibility of in vivo tumor detection using magnetic resonance (MR) molecular imaging with targeted magnetic nanoparticles as imaging probe. Targeted probe was synthesized by covalently linking the recombinant human gonadotropin releasing hormone analog (the targeting portion) with the ultrasmall superparamagnetic iron oxide nanoparticles (the imaging portion). The imaging portion served as the control material. The in vitro tumor cell experiment and the in vivo experiment using nude mice bearing tumors were carried out to test the targeting ability of the probe. In the in vitro experiment, the targeting probe and control materials were incubated separately with A549 cells which had high affinity to gonadotropin releasing hormone. Then the cells were taken out and lysed. The resultant solution was then subjected to MR imaging. The T2 value of the solutions was measured and compared. In the in vivo experiment, the targeting probe was administered into nude mice bearing A549 tumors. Dynamic MR imaging was carried out to measure the signal and T2 value of the tumor. The control material was also administered into control group of nude mice, and dynamic magnetic resonance imaging was performed. The T2 value of the tumor in both groups were recorded and compared. Both the in vitro and in vivo experiments proved the targeting ability of targeted probe. Compared with control material, the targeting probe had higher combining ability with tumor cells. MR molecular imaging of tumor can be realized by using targeting magnetic nanoparticles.

  15. 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.

  16. Labeled Putrescine as a Probe in Brain Tumors

    NASA Astrophysics Data System (ADS)

    Volkow, Nora; Goldman, Stephen S.; Flamm, Eugene S.; Cravioto, Humberto; Wolf, Alfred P.; Brodie, Jonathan D.

    1983-08-01

    The polyamine metabolism of transplanted N-nitrosomethylurea-derived rat glioma was determined with radiolabeled putrescine used as a marker for malignancy. The uptake of putrescine in vivo was complete within 5 minutes and was specific for tumor tissue. The conversion of putrescine to spermine and other metabolites by the tumor was rapid, in contrast to the case for adjacent normal brain. These results suggest that putrescine labeled with carbon-11 may be used as a positron-emission tomographic tracer for the selective metabolic imaging of brain tumor and may be used in an appropriate model as a marker for tumor growth rate.

  17. Peptides as targeting probes against tumor vasculature for diagnosis and drug delivery

    PubMed Central

    2012-01-01

    Tumor vasculature expresses a distinct set of molecule signatures on the endothelial cell surface different from the resting blood vessels of other organs and tissues in the body. This makes them an attractive target for cancer therapy and molecular imaging. The current technology using the in vivo phage display biopanning allows us to quickly isolate and identify peptides potentially homing to various tumor blood vessels. Tumor-homing peptides in conjugation with chemotherapeutic drugs or imaging contrast have been extensively tested in various preclinical and clinical studies. These tumor-homing peptides have valuable potential as targeting probes for tumor molecular imaging and drug delivery. In this review, we summarize the recent advances about the applications of tumor-homing peptides selected by in vivo phage display library screening against tumor vasculature. We also introduce the characteristics of the latest discovered tumor-penetrating peptides in their potential clinical applications. PMID:23046982

  18. Peptides as targeting probes against tumor vasculature for diagnosis and drug delivery.

    PubMed

    Li, Zhi Jie; Cho, Chi Hin

    2012-09-19

    Tumor vasculature expresses a distinct set of molecule signatures on the endothelial cell surface different from the resting blood vessels of other organs and tissues in the body. This makes them an attractive target for cancer therapy and molecular imaging. The current technology using the in vivo phage display biopanning allows us to quickly isolate and identify peptides potentially homing to various tumor blood vessels. Tumor-homing peptides in conjugation with chemotherapeutic drugs or imaging contrast have been extensively tested in various preclinical and clinical studies. These tumor-homing peptides have valuable potential as targeting probes for tumor molecular imaging and drug delivery. In this review, we summarize the recent advances about the applications of tumor-homing peptides selected by in vivo phage display library screening against tumor vasculature. We also introduce the characteristics of the latest discovered tumor-penetrating peptides in their potential clinical applications.

  19. Development of novel nanocarrier-based near-infrared optical probes for in vivo tumor imaging.

    PubMed

    Shimizu, Yoichi; Temma, Takashi; Hara, Isao; Yamahara, Ryo; Ozeki, Ei-ichi; Ono, Masahiro; Saji, Hideo

    2012-03-01

    Optical imaging with near-infrared (NIR) fluorescent probes is a useful diagnostic technology for in vivo tumor detection. Our plan was to develop novel NIR fluorophore-micelle complex probes. IC7-1 and IC7-2 were synthesized as novel lipophilic NIR fluorophores, which were encapsulated in an amphiphilic polydepsipeptide micelle "lactosome". The fluorophore-micelle complexes IC7-1 lactosome and IC7-2 lactosome were evaluated as NIR fluorescent probes for in vivo tumor imaging. IC7-1 and IC7-2 were synthesized and then encapsulated in lactosomes. The optical properties of IC7-1, IC7-2, IC7-1 lactosome and IC7-2 lactosome were measured. IC7-1 lactosome and IC7-2 lactosome were administered to tumor-bearing mice, and fluorescence images were acquired for 48 h. IC7-1 and IC7-2 were successfully synthesized in 12% and 6.3% overall yield, and maximum emission wavelengths in chloroform were observed at 858 nm and 897 nm, respectively. Aqueous buffered solutions of IC7-1 lactosome and IC7-2 lactosome showed similar fluorescence spectra in chloroform and higher or comparable quantum yields and higher photostability compared with ICG. Both lactosome probes specifically visualized tumor tissue 6 h post-administration. IC7-1 lactosome and IC7-2 lactosome could be promising NIR probes for in vivo tumor imaging.

  20. NIR imaging the delivery of cathespin B probe to breast tumors

    NASA Astrophysics Data System (ADS)

    Zhou, Lanlan; Blessington, Dana M.; Zhang, Zhihong; Lindenmayer, Aristid E.; Tung, Ching H.; Weissleder, Ralph; Chance, Britton

    2003-07-01

    Proteases are involved in the invasion and metastasis of tumor cells. Cathepsin B overexpression has been shown in some neoplastic tissues. This study assesses the expression of Cathepsin B in the human fibrosarcoma (HT1080) in the mouse model by near-infrared (NIR) imaging. The nude mice were intravenously injected "a stealth probe" - an activable Cathepsin B sensing near-infrared fluorescence (NIRF) probe (24 hours before sacrifice) and the dye Cy5.5 (30 seconds before sacrifice). The animals were freeze-trapped and NIR images were obtained by the low temperature NIR scanner at the following excitation-emission wavelength pairs: 366, 450nm (NADH), 436, 520nm (FAD), and 670, 695nm (Cathepsin B probe). After imaging, the samples were submitted for histopathological evaluation. The tumor redox ratio NADH/(NADH+FAD) increased significantly because of the hypoxic state of tumor tissue with respect to normal tissue. The Cathepsin B probe was uniformly distributed throughout the tumor. This study indicated the efficient usage of the Cathepsin B probe in the molecular imaging for the detection of the early stage tumors.

  1. Probing the structural and molecular diversity of tumor vasculature.

    PubMed

    Pasqualini, Renata; Arap, Wadih; McDonald, Donald M

    2002-12-01

    The molecular diversity of the vasculature provides a rational basis for developing targeted diagnostics and therapeutics for cancer. Targeted imaging agents would offer better localization of primary tumors and metastases, and targeted therapies would improve efficacy and reduce side effects. The development of targeted pharmaceuticals requires the identification of specific ligand-receptor pairs, and knowledge of their cellular distribution and accessibility. Using in vivo phage display, a technique by which we can identify organ-specific and disease-specific proteins expressed on the endothelial surface, it is now possible to decipher the molecular signature of blood vessels in normal and diseased tissues. These studies have already led to the identification of peptides that target the normal vasculature of the brain, kidney, pancreas, lung and skin, as well as the abnormal vasculature of tumors, arthritis and atherosclerosis. Membrane dipeptidase in the lungs, interleukin-11 receptor in the prostate, and aminopeptidase N in tumors are examples of molecular targets on blood vessels. Corresponding confocal-microscopic imaging and ultrastructural studies are providing a more complete understanding of the cellular abnormalities of tumor blood vessels, and the distribution and accessibility of potential targets. The combined approach offers a strategy for creating a ligand-receptor map of the human vasculature, and forms a foundation for the development and application of targeted therapies in cancer and other diseases.

  2. Numerical sensitivity modeling for the detection of skin tumors by using tetrapolar probe.

    PubMed

    Ramos, Airton; Bertemes-Filho, Pedro

    2011-12-01

    The measurement of electrical impedance of skin using surface electrodes permits the assessment of changes in local properties of the skin and can be used in the detection of tumors. The sensitivity of this technique depends mainly on the geometry of the probe and the size of the tumor. In this article, the impedance method was used to estimate the sensitivity of a tetrapolar probe in detecting small regions of increased conductivity in a stratified model of human skin. The impedance method was used to model the potential distribution using fasorial analysis to solve the node equations of the equivalent circuit. Interpolation was applied to reduce discretization error. The skin was modeled as a three-layer structure with different conductivity and permittivity obtained from the literature. A tumor was modeled as a small volume with admittivity four times higher than the normal tissue. Sensitivity calculation was made as a function of electrode diameter and separation, tumor size, and excitation frequency. The simulations indicated that by inserting a one square millimeter tumor in the epidermis, the load impedance to the current source varies about 1% while the transfer impedance varied 8%. The sensitivity also increases nonlinearly with increasing tumor area and thickness. Additionally, it was found that the sensitivity of the transfer impedance has a maximum value when the electrodes are separated by 1.8 mm. The results show that transfer impedance measurements of the skin may detect small skin tumors with a reasonable sensitivity by using an appropriate tetrapolar probe.

  3. 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

  4. Analysis of the distribution of magnetic fluid inside tumors by a giant magnetoresistance probe.

    PubMed

    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.

  5. FDG-PET probe-guided surgery for recurrent retroperitoneal testicular tumor recurrences.

    PubMed

    de Jong, J S; van Ginkel, R J; Slart, R H J A; Lemstra, C L; Paans, A M J; Mulder, N H; Hoekstra, H J

    2010-11-01

    Tumor marker based recurrences of previously treated testicular cancer are generally detected with CT scan. They sometimes cannot be visualized with conventional morphologic imaging. FDG-PET has the ability to detect these recurrences. PET probe-guided surgery, may facilitate the extent of surgery and optimize the surgical resection. Three patients with resectable 2nd or 3rd recurrent testicular cancer based on elevated tumor markers after previous various chemotherapy schedules and resections of residual retroperitoneal tumor masses were included in this study. A diagnostic FDG-PET was performed and a hotspot in previously operated area of the retroperitoneal space in all three patients was visualized. PET probe-guided surgery was performed using a high-energy gamma probe 3 h post-injection of 500 MBq FDG. All patients showed extended adhesions and scar tissue in the retroperitoneal area due to the previous surgeries. Pre-operative PET/CT scan showed a good correlation with intra-operative PET probe-guided detection of recurrent lesions. There was a high target to background ratio (TGB) of 5:1 during the procedure. In one patient, a 2 cm large lesion, which did not show on pre-operative FDG-PET scan, was detected with the PET probe. Histopathologic tissue evaluation demonstrated recurrent vital tumor in all PET probe positive lesions. PET probe-guided surgery seems to be a promising tool to localize FDG-PET positive lesion in recurrent testicular cancer in hardly accessible surgical locations. PET probe-guided surgery might be a useful technique in surgical oncology for recurrent testicular cancer and has the potential to be applied in surgery of other malignant diseases. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Bioconjugate recognition molecules to quantum dots as tumor probes.

    PubMed

    Liu, Tian-Cai; Wang, Jian-Hao; Wang, Hai-Qiao; Zhang, Hai-Li; Zhang, Zhi-Hong; Hua, Xiao-Feng; Cao, Yuan-Cheng; Zhao, Yuan-Di; Luo, Qing-Ming

    2007-12-15

    Transferrin and mouse anti-human CD71 monoclonal antibody were respectively conjugated covalently to the core/shell CdSe/ZnS quantum dots with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydrocylsulfo-succinimide (Sulfo-NHS). The conjugation worked well and the bioactivities of these macromolecules still remained, which was verified by column filtration, sodium dodecyl sulfate polyacrylamide gel electrophoresis, absorption spectra, fluorescence spectra, and circular dichroism spectrometry. Thus, these two kinds of quantum dot conjugates were used to recognize the tumor cells involved. In case of pseudo positivity, FITC-labeling secondary antibody IgG was used, and the results showed that as-prepared fluorescent quantum dot bioprobes were highly specific to tumor cells.

  7. 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.

  8. Synthesis of a Novel IR-822-Met near-infrared probe for in vivo tumor diagnosis.

    PubMed

    Sun, Chunlong; Zhang, Hongtao; Du, Wen; Wang, Baoqin; Ji, Min

    2017-04-01

    Methionine is a valid target for the treatment of cancer and to achieve in vivo imaging and early diagnosis of tumors, we have synthesized near-infrared (NIR) fluorochrome IR-822-labeled methionine (IR-822-Met). NIR fluorescent dye IR-822 was conjugated with methionine through its amide bond. It had low toxicity to normal cell/tissues. In vitro and in vivo studies demonstrated its high targeting capability to tumors. The results support the potential of using ligand-modified methionine probe for tumor diagnosis and targeted therapy. The probe also exhibited good photostability, and excellent cell membrane permeability. IR-822-Met is a promising imaging agent for tumor diagnosis, especially in their early stage.

  9. Integrated Microfluidic Platform with Multiple Functions To Probe Tumor-Endothelial Cell Interaction.

    PubMed

    Lin, Ling; Lin, Xuexia; Lin, Luyao; Feng, Qiang; Kitamori, Takehiko; Lin, Jin-Ming; Sun, Jiashu

    2017-09-19

    Interaction between tumor and endothelial cells could affect tumor growth and progression and induce drug resistance during cancer therapy. Investigation of tumor-endothelial cell interaction involves cell coculture, protein detection, and analysis of drug metabolites, which are complicated and time-consuming. In this work, we present an integrated microfluidic device with three individual components (cell coculture component, protein detection component, and pretreatment component for drug metabolites) to probe the interaction between tumor and endothelial cells. Cocultured cervical carcinoma cells (CaSki cells) and human umbilical vein endothelial cells (HUVECs) show higher resistance to chemotherapeutic agents than single-cultured cells, indicated by higher cell viability, increased expression of angiogenic proteins, and elevated level of paclitaxel metabolites under coculture conditions. This integrated microfluidic platform with multiple functions facilitates understanding of the interaction between tumor and endothelial cells, and it may become a promising tool for drug screening within an engineered tumor microenvironment.

  10. 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.

  11. Fluorescence microscopy studies of a peripheral-benzodiazepine-receptor-targeted molecular probe for brain tumor imaging

    NASA Astrophysics Data System (ADS)

    Marcu, Laura; Vernier, P. Thomas; Manning, H. Charles; Salemi, Sarah; Li, Aimin; Craft, Cheryl M.; Gundersen, Martin A.; Bornhop, Darryl J.

    2003-10-01

    This study investigates the potential of a new multi-modal lanthanide chelate complex for specifically targeting brain tumor cells. We report here results from ongoing studies of up-take, sub-cellular localization and binding specificity of this new molecular imaging probe. Fluorescence microscopy investigations in living rat C6 glioma tumor cells demonstrate that the new imaging agent has affinity for glioma cells and binds to mitochondria.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. A fluorescent probe to detect thiol-containing amino acids in solid tumors.

    PubMed

    Ren, Wen Xiu; Han, Jiyou; Pradhan, Tuhin; Lim, Ja-Yun; Lee, Jae Hong; Lee, Jaehun; Kim, Jong-Hoon; Kim, Jong Seung

    2014-04-01

    Early detecting of cancer is critical to provide proper treatment and to improve survival of patients. Here, we reported a highly sensitive ratiometric (yellow emission (550 nm) to blue emission (496 nm)) fluorescent probe 1 developed for detection of thiol-containing amino acids. This probe successfully eliminates interference from background autofluorescence, and discriminates between human carcinoma and normal cells by detecting intracellular thiol levels in living cells (P < 0.05). Furthermore, the ability of the probe to identify growing tumors by measuring GSH in the tissues as well as in the fresh blood of tumor xenograft mice. Additionally, the ratio of the emission intensity at two different wavelengths can provide quantitative analysis of glutathione (GSH) in the living systems. It suggests that it represents a promising prognostic and diagnostic marker, with extensive and simple potential clinical applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. High-efficiency FRET-enhanced photoacoustic probes for in vivo tumor imaging

    NASA Astrophysics Data System (ADS)

    Qin, Huan; Liu, Liming

    2017-01-01

    Photoacoustic imaging can provide high-resolution and high-contrast image under unprecedented depth compared with pure optical imaging techniques by making use of laser-induced ultrasound waves. Although a series of absorption-enhanced optical contrast agents for photoacoustic imaging were developed, the probe with fully conversion from absorbed light energy to acoustic energy has not been achieved so far. Here we develop a high-efficiency photoacoustic probes with fluorescence resonance energy transfer (FRET) effect for enhancement of nonradiative energy. Graphene oxide (GO) binding optical dyes (GO-dyes) were achieved to show highly fluorescence quenching and violently increased photoacoustic signal intensity. GO-dyes were constructed and testified for multi-spectral photoacoustic imaging. As a representative probe, GO-Cy7 nanoparticles were used to validate the feasibility of photoacoustic tumor molecular imaging in vivo. Our work demonstrated a new approach to construct high-efficiency FRET-enhanced multi-spectrum probes for photoacoustic molecular imaging.

  20. Electron paramagnetic resonance oxygen imaging of a rabbit tumor using localized spin probe delivery.

    PubMed

    Epel, Boris; Haney, Chad R; Hleihel, Danielle; Wardrip, Craig; Barth, Eugene D; Halpern, Howard J

    2010-06-01

    Application of in vivo electron paramagnetic resonance (EPR) oxygen imaging (EPROI) to tumors larger than those of mice requires development of both instrumental and medical aspects of imaging. 250 MHz EPR oxygen imaging was performed using a loop-gap resonator with a volume exceeding 100 cm3. The paramagnetic spin probe was injected directly into the femoral artery feeding the rabbit leg/tumor. The authors present continuous wave and electron spin echo EPR oxygen images of a large size (4 cm) VX-2 tumor located on the leg of a New Zealand white rabbit. This study demonstrates the feasibility of continuous wave and electron spin echo oxygen imaging modalities for investigation of volumes of tumor and normal tissue relevant to large animals. The injection of the spin probe directly into the artery feeding a rabbit leg will allow one to reduce, by over one order of magnitude, the amount of spin probe used as compared to whole animal i.v. injection.

  1. A fluorescence microscopy study of quantum dots as fluorescent probes for brain tumor diagnosis

    NASA Astrophysics Data System (ADS)

    Wang, Jingjing; Vernier, P. Thomas; Sun, Yinghua; Gundersen, Martin A.; Marcu, Laura

    2005-03-01

    In vivo fluorescent spectroscopy and imaging using endogenous and exogenous sources of contrast can provide new approaches for enhanced demarcation of brain tumor margins and infiltration. Quantum dots (QDs), nanometer-size fluorescent probes, represent excellent contrast agents for biomedical imaging due to their broader excitation spectrum, narrower emission spectra, and higher sensitivity and stability. The epidermal growth factor receptor (EGFR) is implicated in the development and progression of a number of human solid tumors including brain tumors and thus a potential target for brain tumor diagnosis. In this study, we investigate the up-take of ODs by brain tumor cells and the potential use of EGFR-targeted QDs for enhanced optical imaging of brain tumors. We conducted fluorescence microscopy studies of the up-take mechanism of the anti-EGFR-ODs complexes by Human U87, and SKMG-3 glioblastoma cells. Our preliminary results show that QDs can enter into glioma cells through anti-EGFR mediated endocytosis, suggesting that these nano-size particles can tag brain tumor cells.

  2. Two new polyoxometalate tri-supported transition metal complexes constructed from bi-capped Keggin molybdenum vanadium clusters and copper complex fragments

    NASA Astrophysics Data System (ADS)

    Cui, Ji-Wen; Cui, Xiao-Bing; Xu, Jia-Ning; Yu, Hai-Hui; Xu, Ji-Qing; Duan, Wei-Jie; Wang, Tie-Gang

    2008-11-01

    Two new molybdenum-vanadium polyoxometalate tri-supported transition metal complexes [Cu(2,2 '-bipy)] [Cu(2,2 '-bipy) 2] 2[PMo 8V 6O 42]· nH 2O ( n = 1.5 ( 1) and n = 2 ( 2); 2,2 '-bipy = 2,2 '-bipyridine) have been hydrothermally synthesized and characterized by elemental analyses, IR, XPS and single-crystal X-ray diffraction analyses. Both compound 1 and compound 2 contain molybdenum-vanadium polyoxometalates, each of which support one [Cu(2,2 '-bipy)] 2+ cation and two [Cu(2,2 '-bipy) 2] 2+ cations, respectively. The difference between compound 1 and compound 2 is that the polyoxoanion of 1 is a bi-capped α-Keggin cluster and that of 2 is a bi-capped pseudo-Keggin one. Studies of magnetic properties indicated the presence of ferromagnetic behaviors for compounds 1 and 2.

  3. Cellular heterogeneity profiling by hyaluronan probes reveals an invasive but slow-growing breast tumor subset

    PubMed Central

    Veiseh, Mandana; Kwon, Daniel H.; Borowsky, Alexander D.; Tolg, Cornelia; Leong, Hon S.; Lewis, John D.; Turley, Eva A.; Bissell, Mina J.

    2014-01-01

    Tumor heterogeneity confounds cancer diagnosis and the outcome of therapy, necessitating analysis of tumor cell subsets within the tumor mass. Elevated expression of hyaluronan (HA) and HA receptors, receptor for HA-mediated motility (RHAMM)/HA-mediated motility receptor and cluster designation 44 (CD44), in breast tumors correlates with poor outcome. We hypothesized that a probe for detecting HA–HA receptor interactions may reveal breast cancer (BCa) cell heterogeneity relevant to tumor progression. A fluorescent HA (F-HA) probe containing a mixture of polymer sizes typical of tumor microenvironments (10–480 kDa), multiplexed profiling, and flow cytometry were used to monitor HA binding to BCa cell lines of different molecular subtypes. Formulae were developed to quantify binding heterogeneity and to measure invasion in vivo. Two subsets exhibiting differential binding (HA−/low vs. HAhigh) were isolated and characterized for morphology, growth, and invasion in culture and as xenografts in vivo. F-HA–binding amounts and degree of heterogeneity varied with BCa subtype, were highest in the malignant basal-like cell lines, and decreased upon reversion to a nonmalignant phenotype. Binding amounts correlated with CD44 and RHAMM displayed but binding heterogeneity appeared to arise from a differential ability of HA receptor-positive subpopulations to interact with F-HA. HAhigh subpopulations exhibited significantly higher local invasion and lung micrometastases but, unexpectedly, lower proliferation than either unsorted parental cells or the HA−/low subpopulation. Querying F-HA binding to aggressive tumor cells reveals a previously undetected form of heterogeneity that predicts invasive/metastatic behavior and that may aid both early identification of cancer patients susceptible to metastasis, and detection/therapy of invasive BCa subpopulations. PMID:24733940

  4. A novel probe for the non-invasive detection of tumor-associated inflammation

    PubMed Central

    Balducci, Anthony; Wen, Yi; Zhang, Yang; Helfer, Brooke M.; Hitchens, T. Kevin; Meng, Wilson S.; Wesa, Amy K.; Janjic, Jelena M.

    2013-01-01

    A novel dual-mode contrast agent was formulated through the addition of an optical near infrared (NIR) probe to a perfluorocarbon (PFC)-based 19F magnetic resonance imaging (MRI) agent, which labels inflammatory cells in situ. A single PFC-NIR imaging agent enables both a qualitative, rapid optical monitoring of an inflammatory state and a quantitative, detailed and tissue-depth independent magnetic resonance imaging (MRI). The feasibility of in vivo optical imaging of the inflammatory response was demonstrated in a subcutaneous murine breast carcinoma model. Ex vivo optical imaging was used to quantify the PFC-NIR signal in the tumor and organs, and results correlated well with quantitative 19F NMR analyses of intact tissues. 19F MRI was employed to construct a three-dimensional image of the cellular microenvironment at the tumor site. Flow cytometry of isolated tumor cells was used to identify the cellular localization of the PFC-NIR probe within the tumor microenvironment. Contrast is achieved through the labeling of host cells involved in the immune response, but not tumor cells. The major cellular reservoir of the imaging agent were tumor-infiltrating CD11b+ F4/80low Gr-1low cells, a cell subset sharing immunophenotypic features with myeloid-derived suppressor cells (MDSCs). These cells are recruited to sites of inflammation and are implicated in immune evasion and tumor progression. This PFC-NIR contrast agent coupled to non-invasive, quantitative imaging techniques could serve as a valuable tool for evaluating novel anticancer agents. PMID:23526711

  5. 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.

  6. 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

  7. Clonal analysis of human tumors with M27 beta, a highly informative polymorphic X chromosomal probe.

    PubMed Central

    Fey, M F; Peter, H J; Hinds, H L; Zimmermann, A; Liechti-Gallati, S; Gerber, H; Studer, H; Tobler, A

    1992-01-01

    The clonality of human tumors can be studied by X inactivation/methylation analysis in female patients heterozygous for X-linked DNA polymorphisms. We present a detailed study on clonal tumor analysis with M27 beta, a highly informative probe detecting a polymorphic X chromosomal locus, DXS255. The polymorphism detected at this locus is due to variable numbers of tandem repeats. The rate of constitutional heterozygosity detected by M27 beta was 88%. Normal tissue from gastrointestinal mucosa and thyroid showed random, hence polyclonal, patterns. Nonrandom clonal X inactivation was detected in all 22 malignant neoplasms that had been shown to be clonal by other DNA markers, such as antigen receptor gene rearrangements or clonal loss of heterozygosity at 17p and other loci. 16/48 normal blood leukocyte samples (33%) showed considerably skewed X inactivation patterns. Comparison of blood leukocytes and normal tissue indicated that in a given individual, X inactivation patterns may be tissue specific. M27 beta was used to study the clonal composition of 13 benign thyroid nodules from 12 multinodular goiters with rapid recent growth, traditionally termed "adenomas." Nine of them were clonal, whereas four nodules and tissue from a case of Graves' goiter were not, indicating that some, but not all, such thyroid nodules may represent true clonal neoplasms. The M27 beta probe permits one to study the clonal composition by the X inactivation approach of a wide variety of solid tumors from most female patients. As a control, normal tissue homologous to the tumor type of interest is preferable to DNA from blood leukocytes, since the latter may show nonrandom X inactivation patterns in a fairly high proportion of cases. M27 beta may, therefore, be of limited use for the clonal analysis of neoplasms derived from hematopoietic cells. Images PMID:1349026

  8. In Vivo Tumor Secretion Probing Via Ultrafiltration and Tissue Chamber: Implication for Anti-Cancer Drugs Targeting Secretome

    PubMed Central

    Huang, Chun-Ming; Nakatsuji, Teruaki; Liu, Yu-Tseung; Shi, Yang

    2009-01-01

    Tumor secreted proteins/peptides (tumor secretome) act as mediators of tumor-host communication in the tumor microenvironment. Therefore, development of anti-cancer drugs targeting secretome may effectively control tumor progression. Novel techniques including a capillary ultrafiltration (CUF) probe and a dermis-based cell-trapped system (DBCTS) linked to a tissue chamber were utilized to sample in vivo secretome from tumor masses and microenvironments. The CUF probe and tissue chamber were evaluated in the context of in vivo secretome sampling. Both techniques have been successfully integrated with mass spectrometry for secretome identification. A secretome containing multiple proteins and peptides can be analyzed by NanoLC-LTQ mass spectrometry, which is specially suited to identifying proteins in a complex mixture. In the future, the establishment of comprehensive proteomes of various host and tumor cells, as well as plasma will help in distinguishing the cellular sources of secretome. Many detection methods have been patented regarding probes and peptide used for identification of tumors. PMID:18289123

  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. Probe-free allele-specific copy number detection and analysis of tumors.

    PubMed

    Zhu, Ailin; Guan, Xiaowei; Gu, Xinbin; Xie, Guiqin

    2016-03-15

    Cancer development and progression frequently involve nucleotide mutations as well as amplifications and deletions of genomic segments. Quantification of allele-specific copy number is an important step in characterizing tumor genomes for precision medicine. Despite advances in approaches to high-throughput genomic DNA analysis, inexpensive and simple methods for analyzing complex nucleotide and copy number variants are still needed. Real-time polymerase chain reaction (PCR) methods for discovering and genotyping single nucleotide polymorphisms are becoming increasingly important in genetic analysis. In this study, we describe a simple, single-tube, probe-free method that combines SYBR Green I-based quantitative real-time PCR and quantitative melting curve analysis both to detect specific nucleotide variants and to quantify allele-specific copy number variants of tumors. The approach is based on the quantification of the targets of interest and the relative abundance of two alleles in a single tube. The specificity, sensitivity, and utility of the assay were demonstrated in detecting allele-specific copy number changes critical for carcinogenesis and therapeutic intervention. Our approach would be useful for allele-specific copy number analysis or precise genotyping. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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.

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

    PubMed

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

    2015-10-01

    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.

  16. Ultrasensitive Detection of MicroRNA in Tumor Cells and Tissues via Continuous Assembly of DNA Probe.

    PubMed

    Liao, Yuhui; Fu, Yu; Wu, Yunxia; Huang, Ru; Zhou, Xiaoming; Xing, Da

    2015-11-09

    Nucleic acids have been engineered to participate in a wide variety of tasks. Among them, the enzyme-free amplification modes, enzyme-free DNA circuits (EFDCs), and hybridization chain reactions (HCRs) have been widely applied in a series of studies of bioanalysis. We demonstrated here an ultrasensitive hairpin probe-based circulation for continuous assemble of DNA probe. This strategy improved the analyte stability-dependent amplification efficiency of EFDC and signal enhancement without being limited by the analyte's initial concentration, and it was used to produce a novel microRNA (miRNA) trace analysis assay with ultrasensitive amplification properties. Through the detection of standard miRNA substances, 1 amol-level sensitivity and satisfactory specificity were achieved. Compared with EFDCs and HCRs, the sensitivity of ultrasensitive hairpin probe-based circulation was higher by 3 or 4 orders of magnitude. Furthermore, the excellent performance of this platform was also demonstrated in the detection of miRNAs in tumor cells. The sensitivities for the detection of miRNAs in HepG2, A549 and MCF-7 tumor cells were 10, 10, and 100 cells, respectively. In addition, a high detection rate of 83% was achieved for tumor tissues. Thus, this ultrasensitive hairpin probe-based circulation possesses the potential to be a technological innovation in the field of tumor diagnosis.

  17. High-Transmission-Efficiency and Side-Viewing Micro OIDRS Probe for Fast and Minimally-Invasive Tumor Margin Detection

    PubMed Central

    Garcia-Uribe, A.; Chang, C.-C.; Yapici, M. K.; Zou, J.; Banerjee, B.; Kuczynski, J.; Ong, E.; Marner, E. S.; Wang, L. V.

    2011-01-01

    The determination of a cancer free margin I organs is a difficult and time consuming process, with an unmet need for rapid determination of tumor margin at surgery. In this paper, we report the design, fabrication and testing of a novel miniaturized optical sensor probe with “side-viewing” capability. Its unprecedented small size, unique “side-viewing” capability and high optical transmission efficiency enable the agile maneuvering and efficient data collection even in the narrow cavities inside the human body. The sensor probe consists of four micromachined substrates with optical fibers for oblique light incidence and collection of spatially resolved diffuse reflectance from the contacted tissues. The optical sensor probe has been used to conduct the oblique incidence diffuse reflectance spectroscopy (OIDRS) on a human pancreatic specimen. Based on the measurement results, the margin of the malignant tumor has been successfully determined optically, which matches well with the histological results. PMID:21479115

  18. 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

  19. Mono-dispersed high magnetic resonance sensitive magnetite nanocluster probe for detection of nascent tumors by magnetic resonance molecular imaging.

    PubMed

    Zhang, Chunfu; Xie, Xuan; Liang, Sheng; Li, Mingli; Liu, Yajie; Gu, Hongchen

    2012-08-01

    Sensitive molecular imaging and detection of tumors or their supporting neovascularity require high-avidity, target-specific probes, which produce robust signal amplification compatible with a sensitive high-resolution imaging modality. In this context, we fabricated a high magnetic resonance (MR)-sensitive magnetite nanocluster (MNC) probe specific for tumor angiogenesis by assembly of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with (Mal)mPEG-PLA copolymer into cluster and subsequent encoding c(RGDyC) peptide on the cluster (RGD-MNC) for detection of nascent tumors. We found that RGD-MNC is highly sensitive (r(2) = 464.94 s(-1)mM(-1)) and specific for αvβ3-positive cells. Both nascent (35 ± 6.6 mm(3)) and large tumors (256 ± 22.3 mm(3)) can be registered by RGD-MNC and detected by MR imaging (MRI), with the nascent tumors demonstrating more pronounced MR contrast. Immunohistochemical studies revealed that MR signal decrease was closely correlated with histological characteristics of tumors (microvessel density and αvβ3 expression levels) at different growth stages.

  20. Adenovirus replication as an in vitro probe for drug sensitivity in human tumors.

    PubMed

    Parsons, P G; Maynard, K R; Little, J H; McLeod, G R

    1986-04-01

    The feasibility of using adenovirus 5 as an in vitro probe for chemosensitivity in short-term cultures of human tumors was evaluated using human melanoma cell lines and primary cultures of melanoma biopsies. A convenient immunoperoxidase method was developed for quantitating viral replication 2 days after infection. Two different approaches were explored: the host cell reactivation assay (HCR) using drug-treated virus; and the viral capacity assay using drug-treated cells. The HCR assay detected sensitivity to 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC) in Mer- (methyl excision repair deficient) cell lines as decreased ability of the cells to replicate MTIC-treated virus. This test should be applicable to DNA-damaging agents and repair-deficient tumors. Adenovirus replicated readily in nonproliferating primary cultures of melanoma biopsies; application of the HCR assays to this material identified one Mer- sample of 11 tested. Herpes viruses were not suitable for use in HCR because herpes simplex virus type 1 failed to distinguish Mer- from Mer+ melanoma cells; and nonproductive infection of MTIC-sensitive lymphoid cells with Epstein-Barr virus yielded an MTIC-resistant cell line. The second assay (viral capacity) involved determination of the inhibition of replication of untreated virus in treated cells. This approach correctly predicted sensitivity to hydroxyurea and deoxyadenosine in melanoma cell lines when compared with clonogenic survival assay. Viral capacity was also inhibited by cytosine arabinoside, fluorouracil, vincristine, adriamycin, 6-mercaptopurine and ionising radiation, and may therefore be useful for detecting sensitivity to a wide range of antitumor agents.

  1. 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.

  2. 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

  3. Development of Coagulation Factor Probes for the Identification of Procoagulant Circulating Tumor Cells

    PubMed Central

    Tormoen, Garth W.; Cianchetti, Flor A.; Bock, Paul E.; McCarty, Owen J. T.

    2012-01-01

    Metastatic cancer is associated with a hypercoagulable state, and pathological venous thromboembolic disease is a significant source of morbidity and the second leading cause of death in patients with cancer. Here we aimed to develop a novel labeling strategy to detect and quantify procoagulant circulating tumor cells (CTCs) from patients with metastatic cancer. We hypothesize that the enumeration of procoagulant CTCs may be prognostic for the development of venous thrombosis in patients with cancer. Our approach is based on the observation that cancer cells are capable of initiating and facilitating cell-mediated coagulation in vitro, whereby activated coagulation factor complexes assemble upon cancer cell membrane surfaces. Binding of fluorescently labeled, active site-inhibited coagulation factors VIIa, Xa, and IIa to the metastatic breast cancer cell line, MDA-MB-231, non-metastatic colorectal cell line, SW480, or metastatic colorectal cell line, SW620, was characterized in a purified system, in anticoagulated blood and plasma, and in plasma under conditions of coagulation. We conclude that a CTC labeling strategy that utilizes coagulation factor-based fluorescent probes may provide a functional assessment of the procoagulant potential of CTCs, and that this strategy is amenable to current CTC detection platforms. PMID:22973554

  4. 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.

  5. A Novel 99mTc-Labeled Molecular Probe for Tumor Angiogenesis Imaging in Hepatoma Xenografts Model: A Pilot Study

    PubMed Central

    Zhao, Qian; Yan, Ping; Wang, Rong Fu; Zhang, Chun Li; Li, Ling; Yin, Lei

    2013-01-01

    Introduction Visualization of tumor angiogenesis using radionuclide targeting provides important diagnostic information. In previous study, we proved that an arginine-arginine-leucine (RRL) peptide should be a tumor endothelial cell specific binding sequence. The overall aim of this study was to evaluate whether 99mTc-radiolabeled RRL could be noninvasively used for imaging of malignant tumors in vivo, and act as a new molecular probe targeting tumor angiogenesis. Methods The RRL peptide was designed and radiosynthesized with 99mTc by a one-step method. The radiolabeling efficiency and radiochemical purity were then characterized in vitro. 99mTc-RRL was injected intravenously in HepG2 xenograft-bearing BALB/c nude mice. Biodistribution and in vivo imaging were performed periodically. The relationship between tumor size and %ID uptake of 99mTc-RRL was also explored. Results The labeling efficiencies of 99mTc-RRL reached 76.9%±4.5% (n = 6) within 30–60 min at room temperature, and the radiochemical purity exceeded 96% after purification. In vitro stability experiment revealed the radiolabeled peptide was stable. Biodistribution data showed that 99mTc-RRL rapidly cleared from the blood and predominantly accumulated in the kidneys and tumor. The specific uptake of 99mTc-RRL in tumor was significantly higher than that of unlabeled RRL blocking and free pertechnetate control test after injection (p<0.05). The ratio of the tumor-to-muscle exceeded 6.5, tumor-to-liver reached 1.98 and tumor-to-blood reached 1.95. In planar gamma imaging study, the tumors were imaged clearly at 2–6 h after injection of 99mTc-RRL, whereas the tumor was not imaged clearly in blocking group. The tumor-to-muscle ratio of images with 99mTc-RRL was comparable with that of 18F-FDG PET images. Immunohistochemical analysis verified the excessive vasculature of tumor. There was a linear relationship between the tumor size and uptake of 99mTc-RRL with R2 = 0.821. Conclusion 99mTc-RRL can

  6. Catheter probe endoscopic ultrasonography by using cold lubricating jelly-filled method for esophageal subepithelial tumors.

    PubMed

    Ahn, H J; Lee, S J; Park, J K; Jun, B G; Seo, H I; Han, K H; Kim, Y D; Jeong, W J; Cheon, G J

    2017-08-01

    Catheter probe endoscopic ultrasonography (C-EUS) by ultrasonographic jelly-filled method has been used to evaluate esophageal subepithelial tumors (SETs). Ultrasonographic jelly is safe on the skin, but its internal safety has not been demonstrated. The jelly stored at room temperature is easily injected into the esophagus through the instrument channel of the endoscope. However, using jelly stored at room temperature remains problematic because the jelly is drained rapidly. We used cold lubricating jelly and an intravenous extension tube to resolve these problems. In this study, we evaluated the safety and efficacy of cold lubricating jelly-filled method. The medical records of patients who underwent C-EUS by using water or cold lubricating jelly-filled method for esophageal SETs from March 2013 to September 2016 in Gangneung Asan hospital were reviewed. Clinical characteristics and EUS findings were evaluated retrospectively. Image quality and procedure time between water and cold lubricating jelly-filled method were compared retrospectively. This study included 138 patients (74 males, 64 females) with esophageal SET with a mean age of 57.1 ± 11.1 years. Thirty-four patients had lesions in the upper esophagus, 58 patients had lesions in the middle esophagus, and 46 patients had lesions in the lower esophagus. The EUS diagnoses were leiomyoma (82.6%), hemangioma (4.3%), extrinsic compressive lesion (3.6%), granulosa cell tumor (2.9%), ectopic calcification (1.4%), cyst (1.4%), lipoma (0.7%), varix (0.7%), and inconclusive lesion (2.2%). The mean image score in the cold lubricating jelly filled-method group was higher than that in the water-filled method group (3.2 ± 0.7 vs. 2.8 ± 0.7, P = 0.002). The procedure time in the cold lubricating jelly filled-method group was shorter than that in the water-filled method group (10 minutes 27 seconds ± 4 minutes 22 seconds versus 13 minutes 20 seconds ± 6 minutes 20 seconds, P = 0.045). No procedure

  7. Optical Aptamer Probes of Fluorescent Imaging to Rapid Monitoring of Circulating Tumor Cell

    PubMed Central

    Hwang, Ji Yeon; Kim, Sang Tae; Han, Ho-Seong; Kim, Kyunggon; Han, Jin Soo

    2016-01-01

    Fluorescence detecting of exogenous EpCAM (epithelial cell adhesion molecule) or muc1 (mucin1) expression correlated to cancer metastasis using nanoparticles provides pivotal information on CTC (circulating tumor cell) occurrence in a noninvasive tool. In this study, we study a new skill to detect extracellular EpCAM/muc1 using quantum dot-based aptamer beacon (QD-EpCAM/muc1 ALB (aptamer linker beacon). The QD-EpCAM/muc1 ALB was designed using QDs (quantum dots) and probe. The EpCAM/muc1-targeting aptamer contains a Ep-CAM/muc1 binding sequence and BHQ1 (black hole quencher 1) or BHQ2 (black hole quencher2). In the absence of target EpCAM/muc1, the QD-EpCAM/muc1 ALB forms a partial duplex loop-like aptamer beacon and remained in quenched state because the BHQ1/2 quenches the fluorescence signal-on of the QD-EpCAM/muc1 ALB. The binding of EpCAM/muc1 of CTC to the EpCAM/muc1 binding aptamer sequence of the EpCAM/muc1-targeting oligonucleotide triggered the dissociation of the BHQ1/2 quencher and subsequent signal-on of a green/red fluorescence signal. Furthermore, acute inflammation was stimulated by trigger such as caerulein in vivo, which resulted in increased fluorescent signal of the cy5.5-EpCAM/muc1 ALB during cancer metastasis due to exogenous expression of EpCAM/muc1 in Panc02-implanted mouse model. PMID:27886058

  8. 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.

  9. A sandwiched biological fluorescent probe for the diagnosis of human ovarian tumor based on TiO2 nanoparticles.

    PubMed

    Zhu, Peisi; Huang, Shasheng; Li, Mengyao; Ding, Na; Peng, Bing; Kong, Lingmi; Bo, Yang

    2011-01-01

    In this paper, we report a novel biological fluorescent probe for the diagnosis of human ovarian tumor based on sandwiched TiO(2) nanoparticles. The fluorescence nanoparticles consist of a fluorescent molecule, tetramethyl rhodamine isothiocyanate (TRITC), sandwiched between titanium dioxide (TiO(2)) nanoparticles and nano-gold via reacting with each other. The antibodies HER2, labeled on the surface of the biofluorescence nanoparticles, have granted nanoparticles the privilege of aiming at peculiar tumor antigen. The specificity of antibody-nanoparticles interacting with cells was characterized by Laser Scanning Confocal Microscope. The results showed that these sandwiched nanoparticles were innocuous and stable, and the method offered potential advantages of sensitivity and simplicity due to high combing efficiency between nanoparticles and cells and provided an alternative method for the diagnosis of human ovarian tumor (HOT).

  10. Clinical superficial Raman probe aimed for epithelial tumor detection: Phantom model results

    PubMed Central

    Agenant, Michelle; Grimbergen, Matthijs; Draga, Ronald; Marple, Eric; Bosch, Ruud; van Swol, Christiaan

    2014-01-01

    Abstract: A novel clinical Raman probe for sampling superficial tissue to improve in vivo detection of epithelial malignancies is compared to a non-superficial probe regarding depth response function and signal-to-noise ratio. Depth response measurements were performed in a phantom tissue model consisting of a polyethylene terephthalate disc in an 20%-Intralipid® solution. Sampling ranges of 0-200 and 0-300 μm were obtained for the superficial and non-superficial probe, respectively. The mean signal-to-noise ratio of the superficial probe increased by a factor of 2 compared with the non-superficial probe. This newly developed superficial Raman probe is expected to improve epithelial cancer detection in vivo. PMID:24761301

  11. 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.

  12. Intraoperative gamma hand-held probe navigation in resection of osteoid osteoma tumor--report of two cases.

    PubMed

    Cengić, Tomislav; Corluka, Stipe; Petrović, Tadija; Baranović, Senka; Kovacić, Ksenija; Kolundzić, Robert

    2013-06-01

    Two cases of osteoid osteoma tumor (OO) are presented and our early experience with intraoperative gamma probing to localize OO during surgery is reported. The concept of radioguided surgery was developed 60 years ago and the gamma detection probe technology for radioguided biopsy and/or resection of bone lesions has been applied since the early 1980s. Bone scintigraphy is very important for initial diagnosis of OO with almost 100% sensitivity. The bone scan finding is specific, with so called double density appearance, very intense accumulation of radiopharmaceutical in the nidus and therefore great difference between the nidus and the surrounding healthy bone, thus making possible to treat this lesion with probe guided surgery. Three phase bone scintigraphy and single photon emission computed tomography were conducted in our patients for initial diagnosis of OO. A second bone scintigraphy was performed before surgery. The surgery followed 12-15 hours later by intraoperative nidus detection with a hand-held gamma probe. Gamma hand-held probe is a system that detects gamma photons. The count rate in the nidus area on the day of surgery was 3 to 4 times higher than in the healthy bone area. Drilling was performed until the counts decreased to the level of the surrounding bone counts, thereby confirming complete excision. This is the method of choice for minimizing bone resection, the risk of pathologic fracture, the need of bone grafting, and reducing the period of convalescence. Evidence for the treatment efficiency is pain disappearance after the surgery.

  13. Tumor homing peptides as molecular probes for cancer therapeutics, diagnostics and theranostics.

    PubMed

    Gautam, A; Kapoor, P; Chaudhary, K; Kumar, R; Raghava, G P S

    2014-01-01

    Cancer is one of the leading causes of mortality worldwide, with more than 10 million new cases each year. Despite the presence of several anticancer agents, cancer treatment is still not very effective. Main reasons behind this high mortality rate are the lack of screening tests for early diagnosis, and non-availability of tumor specific drug delivery system. Most of the current anticancer drugs are unable to differentiate between cancerous and normal cells, leading to systemic toxicity, and adverse side effects. In order to tackle this problem, a considerable progress has been made over the years to identify peptides, which specifically bind to the tumor cells, and tumor vasculature (tumor homing peptides). With the advances in phage display technology, and combinatorial libraries like one-bead one-compound library, several hundreds of tumor homing peptides, and their derivatives, which have potential to detect tumor in vivo, and deliver anticancer agents specifically to the tumor site, have been discovered. Currently, many tumor homing peptide-based therapies for cancer treatment and diagnosis are being tested in various phases of clinical trials. In this review, we have discussed the progress made so far in the identification of tumor homing peptides, and their applications in cancer therapeutics, diagnosis, and theranostics. In addition, a brief discussion on tumor homing peptide resource, and in silico designing of tumor homing peptides has also been provided.

  14. (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. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 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

  16. pHLIP-FIRE, a cell insertion-triggered fluorescent probe for imaging tumors demonstrates targeted cargo delivery in vivo.

    PubMed

    Karabadzhak, Alexander G; An, Ming; Yao, Lan; Langenbacher, Rachel; Moshnikova, Anna; Adochite, Ramona-Cosmina; Andreev, Oleg A; Reshetnyak, Yana K; Engelman, Donald M

    2014-11-21

    We have developed an improved tool for imaging acidic tumors by reporting the insertion of a transmembrane helix: the pHLIP-Fluorescence Insertion REporter (pHLIP-FIRE). In acidic tissues, such as tumors, peptides in the pHLIP family insert as α-helices across cell membranes. The cell-inserting end of the pHLIP-FIRE peptide has a fluorophore-fluorophore or fluorophore-quencher pair. A pair member is released by disulfide cleavage after insertion into the reducing environment inside a cell, resulting in dequenching of the probe. Thus, the fluorescence of the pHLIP-FIRE probe is enhanced upon cell-insertion in the targeted tissues but is suppressed elsewhere due to quenching. Targeting studies in mice bearing breast tumors show strong signaling by pHLIP-FIRE, with a contrast index of ∼17, demonstrating (i) direct imaging of pHLIP insertion and (ii) cargo translocation in vivo. Imaging and targeted cargo delivery should each have clinical applications.

  17. One-dimensional coordination polymers constructed from bicapped Keggin polyoxometalate and cyclic tetranuclear Cu I cluster bridged by asymmetrical bipyridine derivative

    NASA Astrophysics Data System (ADS)

    Tian, Aixiang; Han, Zhangang; Peng, Jun; Sha, Jingquan; Zhao, Yulong; Pang, Haijun; Zhang, Pengpeng; Zhu, Min

    2008-10-01

    This article reports two new bicapped Keggin-based hybrid compounds, {[Cu 4I(cppy) 4][PMo 7VIMo 5VO 40(V IVO) 2]}·2H 2O ( 1) and {[Cu 4I(cppy) 4][SiMo 8VIMo 4VO 40(V IVO) 2]}·2H 2O ( 2) (cppy = 4-(5-(4-chlorophenyl)pyridin-2-yl)pyridine), synthesized under hydrothermal conditions and characterized by X-ray single-crystal diffraction, elemental analyses, IR, XPS, TG and CV analyses. Structural characterization shows that the two compounds are isostructural, consisting of square tetranuclear [Cu 4I(cppy) 4] 4+ circuits and reduced bivanadyl Keggin clusters. The tetranuclear [Cu 4I(cppy) 4] 4+ circuit is 'windstick'-style. The polyoxoanions acting as junctures connect the tetranuclear circuits to construct a chain. These chains are further connected through π⋯π interactions, halogen bonding and hydrogen bonding interactions to construct a 3D superamolecular structure. The electrochemical behaviors of the 1-CPE have been studied in detail.

  18. Synthesis of well-defined bicapped octahedral iron clusters [((tren) L)2 Fe8 (PMe2 Ph)2 ](n) (n=0, -1).

    PubMed

    Sánchez, Raúl Hernández; Willis, Alexander M; Zheng, Shao-Liang; Betley, Theodore A

    2015-10-05

    The synthesis of polynuclear clusters with control over size and cluster geometry remains an unsolved challenge. Herein, we report the synthesis and characterization of open-shell octairon clusters supported by two heptaamine ligands [o-H2 NC6 H4 NH(CH2 )2 ]3 N ((tren) LH9 ). The crystal structure of the all-ferrous species ([(tren) L)2 Fe8 (PMe2 Ph)2 ] (1) displays a bicapped octahedral geometry with FeFe distances ranging from 2.4071(6) to 2.8236(5) Å, where the ligand amine units are formally in amine, amide, and imide oxidation states. Several redox states of the octairon cluster are accessible, as ascertained using cyclic voltammetry. The one-electron-reduced clusters [M](+) [((tren) L)2 Fe8 (PMe2 Ph)2 ](-) (M=Bu4 N (2 a); (15-crown-5)Na(thf) (2 b)) were isolated and characterized. Variable-temperature magnetic susceptibility data indicates that the exchange coupling within the [Fe8 ] core is antiferromagnetic which is attenuated upon reduction to the mixed valent anion.

  19. Synthesis of well-defined bicapped-octahedral iron clusters [(trenL)2Fe8(PMe2Ph)2]n (n = 0, −1)

    PubMed Central

    Hernández Sánchez, Raúl; Willis, Alexander M.; Zheng, Shao-Liang; Betley, Theodore A.

    2015-01-01

    The synthesis of polynuclear clusters with control over size and cluster geometry remains an unsolved challenge. Herein, we report the synthesis and characterization of open-shell octairon clusters subtended by two heptaamine ligands, trenLH9. The molecular crystal structure of the all-ferrous species (trenL)2Fe8(PMe2Ph)2 (1) displays a bicapped-octahedral geometry with Fe–Fe distances ranging from 2.4071(6) to 2.8236(5) Å, where the ligand amine units are formally in amine, amide, and imide oxidation states. Several redox states of the octairon cluster are accessible as ascertained via cyclic voltammetry. The one-electron reduced clusters [M]+[(trenL)2Fe8(PMe2Ph)2]− (M = Bu4N 2a, (15-crown-5)Na(THF) 2b) were isolated and fully characterized. Variable-temperature magnetic susceptibility data indicates that the overall interaction within the [Fe8] core is antiferromagnetic (AF) and magnetometry reveals an S = 2 spin ground state and a Curie constant (θ) of −204.3. The intracore AF coupling decreases substantially in the mixed valence compound 2a (θ = −61.7). The synthetic methodology reported here could be employed to build even larger clusters. PMID:26298064

  20. Multimodal fiber-probe spectroscopy for the diagnostics and classification of bladder tumors

    NASA Astrophysics Data System (ADS)

    Anand, Suresh; Cicchi, Riccardo; Fantechi, Riccardo; Gacci, Mauro; Nesi, Gabriella; Carini, Marco; Pavone, Francesco S.

    2017-02-01

    The gold standard for the detection of bladder cancer is white light cystoscopy, followed by an invasive biopsy and pathological examination. Tissue pathology is time consuming and often prone to sampling errors. Recently, optical spectroscopy techniques have evolved as promising techniques for the detection of neoplasia. The specific goal of this study is to evaluate the application of combined auto-fluorescence (excited using 378 nm and 445 nm wavelengths) and diffuse reflectance spectroscopy to discriminate normal bladder tissue from tumor at different grades. The fluorescence spectrum at both excitation wavelengths showed an increased spectral intensity in tumors with respect to normal tissues. Reflectance data indicated an increased reflectance in the wavelength range 610 nm - 700 nm for different grades of tumors, compared to normal tissues. The spectral data were further analyzed using principal component analysis for evaluating the sensitivity and specificity for diagnosing tumor. The spectral differences observed between various grades of tumors provides a strong genesis for the future evaluation on a larger patient population to achieve statistical significance. This study indicates that a combined spectroscopic strategy, incorporating fluorescence and reflectance spectroscopy, could improve the capability for diagnosing bladder tumor as well as for differentiating tumors in different grades.

  1. In Vivo Tumor Angiogenesis Imaging Using Peptide-Based Near-Infrared Fluorescent Probes.

    PubMed

    Huang, Rui; Conti, Peter S; Chen, Kai

    2016-01-01

    Near-infrared fluorescence (NIRF) imaging is an emerging imaging technique for studying diseases at the molecular level. Optical imaging with a near-infrared emitting fluorophore for targeting tumor angiogenesis offers a noninvasive method for early tumor detection and efficient monitoring of tumor response to anti-angiogenesis therapy. CD13 receptor, a zinc-dependent membrane-bound ectopeptidase, plays important roles in regulating tumor angiogenesis and the growth of new blood vessels. In this chapter, we use CD13 receptor as an example to demonstrate how to construct CD13-specific NGR-containing peptides via bioorthogonal click chemistry for visualizing and quantifying the CD13 receptor expression in vivo by means of NIRF optical imaging.

  2. 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

  3. SELEX aptamer used as a probe to detect circulating tumor cells in peripheral blood of pancreatic cancer patients.

    PubMed

    Zhang, Jinqiang; Li, Shaohua; Liu, Fang; Zhou, Lanping; Shao, Ningsheng; Zhao, Xiaohang

    2015-01-01

    Many studies have shown that the quantity and dynamics of circulating tumor cells (CTCs) in peripheral blood of patients afflicted with solid tumours have great relevance in therapeutic efficacy and prognosis. Different methods based on various strategies have been developed to isolate and identify CTCs, but their efficacy needs to be improved because of the rarity and complexity of CTCs. This study was designed to examine the possibility of using a SELEX aptamer (BC-15) as a probe to identify rare CTCs out of background nucleated cells. Aptamer BC-15 was selected from a random oligonucleotide library screened against human breast cancer tissue. Fluorescence staining showed that BC-15 had a high affinity for nuclei of human cancer cell lines of various origins as well as CTCs isolated from pancreatic cancer patients, whereas its binding capacity for non-tumor breast epithelial cells and leukocytes was almost undetectable. BC-15+/CD45- cells in cancer patient blood were also found to be cytokeratins 18-positive and aneuploid by immunofluorescence staining and fluorescent in situ hybridization, respectively. Finally, the aptamer method was compared with the well-established anti-cytokeratin method using 15 pancreatic cancer patient blood samples, and enumeration indicated no difference between these two methods. Our study establishes a novel way to identify CTCs by using a synthetic aptamer probe. This new approach is comparable with the anti-cytokeratin-based CTC identification method.

  4. 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).

  5. 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.

  6. RGD-conjugated Two-photon Absorbing Near-IR Emitting Fluorescent Probes for Tumor Vasculature Imaging

    PubMed Central

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

    2015-01-01

    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. PMID:26351137

  7. A simple optical fibre probe for differentiation between healthy and tumorous tissue

    NASA Astrophysics Data System (ADS)

    Schartner, Erik P.; Henderson, Matthew R.; Purdey, Malcolm; Monro, Tanya M.; Gill, P. Grantley; Callen, David F.

    2016-11-01

    Incomplete removal of malignant tumours continues to be a significant issue in cancer surgery. It increases the risk of local recurrence and impaired survival, and results in the need for additional surgery with associated attendant costs and morbidity. While pathological methods exist to determine tissue type during surgery, these methods can compromise post-operative pathology, have a lag of minutes to hours before the surgeon receives the results of the tissue analysis and are restricted to excised tissue. In this work we report the development of an optical fibre probe which could find use as an aid for margin detection during surgery. A fluorophore doped polymer coating is deposited on the tip of an optical fibre, which can then be used to record the pH by monitoring the emission spectra from the embedded indicator. The pH values of unknown tissue are measured and compared to healthy tissue, allowing for discrimination between healthy and cancerous tissue. The probe developed here shows strong potential for use during surgery, as the probe design can be readily adapted to a low-cost portable configuration which could find use in the operating theatre. Use of this probe in surgery either on excised or in-vivo tissue has the potential to improve success rates for complete removal of cancers.

  8. A DTI Study to Probe Tumor Microstructure And Its Connection With Hypoxia

    PubMed Central

    Majumdar, Shreyan; Triplett, William; Epel, Boris; Halpern, Howard

    2015-01-01

    Solid tumors have chaotic organization of blood vessels, disruptive nerve paths and muscle fibers that result in a hostile and heterogeneous microenvironment. These tumor regions are often hypoxic and resistant to radiation therapy. The knowledge of partial pressure of oxygen concentration (pO2), in conjunction with the information about tissue organization, can predict tissue health and may eventually be used in combination with intensity-modulated radiation therapy (IMRT) for targeted destruction of radiation-resistant areas, while sparing healthy tissues. Diffusion tensor imaging (DTI) based parameter fractional anisotropy (FA) can be used to assess organization of tissue microstructure, whereas the pO2 can be measured using electron paramagnetic resonance oxygen imaging (EPROI). This study is our first step to connect these two important physiological parameters. We calculated FA in fixed fibrosarcoma (FSa) grown in hind leg of nude mice (n = 6) using preclinical 9.4 T MRI. The FA in tumor region (0.34 ± 0.014) was found to be lower when compared to normal surrounding region (0.36 ± 0.013). We hypothesized that the change in FA is directly correlated with the change in oxygen concentration in tumor. We present preliminary in vivo results showing a positive correlation (R = 0.85, p = 0.017) between the FA and pO2 values acquired for MCa4 tumor (n = 1) using DTI and EPROI. PMID:25570064

  9. Magnetic/upconversion fluorescent NaGdF4:Yb,Er nanoparticle-based dual-modal molecular probes for imaging tiny tumors in vivo.

    PubMed

    Liu, Chunyan; Gao, Zhenyu; Zeng, Jianfeng; Hou, Yi; Fang, Fang; Li, Yilin; Qiao, Ruirui; Shen, Lin; Lei, Hao; Yang, Wensheng; Gao, Mingyuan

    2013-08-27

    Detection of early malignant tumors remains clinically difficult; developing ultrasensitive imaging agents is therefore highly demanded. Owing to the unusual magnetic and optical properties associated with f-electrons, rare-earth elements are very suitable for creating functional materials potentially useful for tumor imaging. Nanometer-sized particles offer such a platform with which versatile unique properties of the rare-earth elements can be integrated. Yet the development of rare-earth nanoparticle-based tumor probes suitable for imaging tiny tumors in vivo remains difficult, which challenges not only the physical properties of the nanoparticles but also the rationality of the probe design. Here we report new approaches for size control synthesis of magnetic/upconversion fluorescent NaGdF4:Yb,Er nanocrystals and their applications for imaging tiny tumors in vivo. By independently varying F(-):Ln(3+) and Na(+):Ln(3+) ratios, the size and shape regulation mechanisms were investigated. By replacing the oleic acid ligand with PEG2000 bearing a maleimide group at one end and two phosphate groups at the other end, PEGylated NaGdF4:Yb,Er nanoparticles with optimized size and upconversion fluorescence were obtained. Accordingly, a dual-modality molecular tumor probe was prepared, as a proof of concept, by covalently attaching antitumor antibody to PEGylated NaGdF4:Yb,Er nanoparticles through a "click" reaction. Systematic investigations on tumor detections, through magnetic resonance imaging and upconversion fluorescence imaging, were carried out to image intraperitoneal tumors and subcutaneous tumors in vivo. Owing to the excellent properties of the molecular probes, tumors smaller than 2 mm was successfully imaged in vivo. In addition, pharmacokinetic studies on differently sized particles were performed to disclose the particle size dependent biodistributions and elimination pathways.

  10. Minimally invasive probe system capable of performing both cryosurgery and hyperthermia treatment on target tumor in deep tissues.

    PubMed

    Liu; Zhou; Yu; Gui; Deng; Lv

    2004-02-01

    Cryosurgery is a clinical therapy aiming at the destruction of diseased target tissues through a controlled deep freezing and subsequent rewarming. It has recently been realized that freezing immediately followed by a rapid and strong heating of the target tissues would significantly improve the treatment effect. However, most of the currently available cryoprobe systems are only capable of performing a single freezing function. To accommodate to the rapid growth of the combined freezing and heating therapy of tumor treatment, we have developed a new cryoprobe system with a powerful heating feature, which can be conveniently applied to destroy the tumor in deep tissue using a minimally invasive approach. Its operation performance will be characterized through a series of experimental tests in air, water, phantom gel, in vitro tissues and rabbits under anaesthesia. This system is perhaps the first one aiming at performing both cryosurgery and hyperthermia on target tumors. Therefore, it provides the clinicians with more choices and algorithms on treating a specific diseased tissue. Further, strain sensors and thermocouples were applied to simultaneously record the transient temperature and the thermal stress fields over the tissues subjected to freezing and strong heating. It was observed that a sudden change in the transient thermal stress was often induced when phase change occurs, which may imply that an evident thermal stress occurs at the liquid-solid interface. This modifies the commonly accepted viewpoint that no stress should exist at the liquid-like phase change interface. Further, implementations of this new system in clinical cryosurgery or hyperthermia are discussed. In addition to the applications in tumor treatment, the present system can also be very useful in fundamental research such as revealing the thermal stress mechanisms in tissues due to quick freezing and heating, which is hard to do otherwise. One interesting result presented in this

  11. A new fluorescent probe with a large turn-on signal for imaging nitroreductase in tumor cells and tissues by two-photon microscopy.

    PubMed

    Liu, Zhan-Rong; Tang, Yonghe; Xu, An; Lin, Weiying

    2017-03-15

    Hypoxia is the important characteristic of solid tumors, and it may cause the bioactivity of nitroreductase (NTR) to display an elevated level. Hence, the development of effective monitoring methods of NTR in living systems is of great importance for detecting the occurrence and progress of tumors. Toward this goal, a novel two-photon fluorescence turn-on NTR probe GCTPOC-HY, based on the two-photon platform GCTPOC and the NTR recognition site p-nitrobenzyl ether, is designed and synthesized. The probe GCTPOC-HY exhibits eminent properties such as high sensitivity and selectivity, highly stable photo-stability, and low cytotoxicity. Besides, the probe responds to 1.5μg/mL NTR with a 130-fold fluorescence enhancement, which is larger than the reported two-photon fluorescent NTR probes. Moreover, the probe GCTPOC-HY is suitable for fluorescence imaging of NTR in living cells by one- and two-photon modes. Importantly, the probe GCTPOC-HY is successfully applied to monitor NTR in the tumor tissues with a significant fluorescence signal and a penetration depth of 70µm by using two-photon microscopy. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Probing Androgen Receptor Signaling in Circulating Tumor Cells in Prostate Cancer

    DTIC Science & Technology

    2013-07-01

    4 , Sridhar Ramaswamy 1 , 4 , Mehmet Toner 2 , 5 , Shyamala Maheswaran 1 , 5 , and Daniel A. Haber 1 , 4 , 8 Authors’ Affi liations: 1...4 Shyamala Maheswaran,2,7 Ravi Kapur,1 Daniel A. Haber,2,5,6 Mehmet Toner1,7† o n A pr il 21 , 2 01 3 ag .o rgCirculating tumor cells (CTCs) are

  13. Highly sensitive detection of multiple tumor markers for lung cancer using gold nanoparticle probes and microarrays.

    PubMed

    Gao, Wanlei; Wang, Wentao; Yao, Shihua; Wu, Shan; Zhang, Honglian; Zhang, Jishen; Jing, Fengxiang; Mao, Hongju; Jin, Qinghui; Cong, Hui; Jia, Chunping; Zhang, Guojun; Zhao, Jianlong

    2017-03-15

    Assay of multiple serum tumor markers such as carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (CYFRA21-1), and neuron specific enolase (NSE), is important for the early diagnosis of lung cancer. Dickkopf-1 (DKK1), a novel serological and histochemical biomarker, was recently reported to be preferentially expressed in lung cancer. Four target proteins were sandwiched by capture antibodies attached to microarrays and detection antibodies carried on modified gold nanoparticles. Optical signals generated by the sandwich structures were amplified by gold deposition with HAuCl4 and H2O2, and were observable by microscopy or the naked eye. The four tumor markers were subsequently measured in 106 lung cancer patients and 42 healthy persons. The assay was capable of detecting multiple biomarkers in serum sample at concentration of <1 ng mL(-1) in 1 h. Combined detection of the four tumor markers highly improved the sensitivity (to 87.74%) for diagnosis of lung cancer compared with sensitivity of single markers. A rapid, highly sensitive co-detection method for multiple biomarkers based on gold nanoparticles and microarrays was developed. In clinical use, it would be expected to improve the early diagnosis of lung cancer.

  14. αvβ3-Integrin-targeting lanthanide complex: synthesis and evaluation as a tumor-homing luminescent probe.

    PubMed

    Ito, Takeo; Inoue, Masaki; Akamatsu, Kanako; Kusaka, Eriko; Tanabe, Kazuhito; Nishimoto, Sei-ichi

    2011-06-15

    The application of lanthanide complexes in the time-resolved fluorescence imaging of living cells has emerged in the last few decades, providing high-contrast images of cells through detection of the delayed emission. In the present study, we synthesized novel trivalent lanthanide complexes containing the cyclic peptide c(RGDfK) to visualize the α(v)β(3)-integrin-expressing tumor cells. Conjugation of c(RGDfK) with the macrocyclic bipyridine ligand had little effect on the fluorescence properties of the complex, indicating that the coordinated lanthanide ion was well isolated from the peptide. Bright luminescence images of α(v)β(3)-integrin-expressing U87-MG cells were successfully obtained by employing the probes.

  15. Development of Molecular Probes Based on Iron Oxide Nanoparticles for in Vivo Magnetic Resonance/Photoacoustic Dual Imaging of Target Molecules in Tumors.

    PubMed

    Sano, Kohei

    2017-01-01

     Molecular imaging probes that enable seamless diagnoses of tumors in the preoperative and intraoperative stages could lead to surgical resection of tumors based on highly accurate diagnoses. Because iron oxide nanoparticles (IONPs) have high proton relaxivity and high molar extinction coefficients suitable for magnetic resonance imaging (MRI) and photoacoustic imaging, respectively, we planned to develop molecular imaging probes applicable to the pre- (MRI) and intraoperative (photoacoustic imaging) stages. Human epidermal growth factor receptor 2 (EGFR2; HER2) was selected as a target molecule, and we designed IONPs (20, 50, and 100 nm) conjugated with anti-HER2 moieties [whole IgG (trastuzumab), single-chain fragment variable (scFv), and peptide] for HER2-targeted tumor imaging. Among the probes tested, scFv-conjugated IONPs (scFv-IONPs) (20 nm) exhibited the highest binding affinity to HER2 (Kd=0.01 nM). An in vivo biodistribution study using (111)In-labeled probes demonstrated that more scFv-IONPs (20 nm) accumulated in HER2-positive than in HER2-negative tumors, suggesting that the uptake of scFv-IONPs is HER2 specific. The scFv-IONPs (20 nm) showed high proton relaxivity and a probe concentration-dependent photoacoustic signal. In vivo MR/photoacoustic imaging studies using scFv-IONPs (20 nm) facilitated HER2-specific visualization of tumors. Furthermore, an iron-staining study demonstrated that the uptake of scFv-IONPs was notable only in HER2-positive tumors. These results suggest that scFv-IONPs (20 nm) may be useful for MR/photoacoustic dual imaging, which could achieve seamless diagnoses in the preoperative and intraoperative stages.

  16. A concise review of magnetic resonance molecular imaging of tumor angiogenesis by targeting integrin αvβ3 with magnetic probes.

    PubMed

    Liu, Yajie; Yang, Yi; Zhang, Chunfu

    2013-01-01

    Angiogenesis is an essential step for the growth and spread of malignant tumors. Accurate detection and quantification of tumor angiogenesis is important for early diagnosis of cancers as well as post therapy assessment of antiangiogenic drugs. The cell adhesion molecule integrin αvβ3 is a specific marker of angiogenesis, which is highly expressed on activated and proliferating endothelial cells, but generally not on quiescent endothelial cells. Therefore, in recent years, many different approaches have been developed for imaging αvβ3 expression, for the detection and characterization of tumor angiogenesis. The present review provides an overview of the current status of magnetic resonance molecular imaging of integrin αvβ3, including the new development of high sensitive contrast agents and strategies for improving the specificity of targeting probes and the biological effects of imaging probes on αvβ3 positive cells.

  17. 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.

  18. 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.

  19. 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.

  20. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Tumor

    MedlinePlus

    ... excessively in the body. Normally, the body controls cell growth and division. New cells are created to replace ... room for healthy replacements. If the balance of cell growth and death is disturbed, a tumor may form. ...

  2. Tethered Hsp90 Inhibitors Carrying Optical or Radioiodinated Probes Reveal Selective Internalization of Ectopic Hsp90 in Malignant Breast Tumor Cells

    PubMed Central

    Barrott, Jared J.; Hughes, Philip F.; Osada, Takuya; Yang, Xiao-Yi; Hartman, Zachary C.; Loiselle, David R.; Spector, Neil L.; Neckers, Len; Rajaram, Narasimhan; Hu, Fangyao; Ramanujam, Nimmi; Vaidyanathan, Ganesan; Zalutsky, Michael R.; Lyerly, H. Kim; Haystead, Timothy A.

    2013-01-01

    Summary Hsp90 inhibitors have demonstrated unusual selectivity for tumor cells despite its ubiquitous expression. This phenomenon has remained unexplained but could be influenced by ectopically expressed Hsp90 in tumors. We have synthesized novel Hsp90 inhibitors that can carry optical or radioiodinated probes via a PEG tether. We show that these tethered inhibitors selectively recognize cells expressing ectopic Hsp90 and become internalized. The internalization process is blocked by Hsp90 antibodies, suggesting that active cycling of the protein is occurring at the plasma membrane. In mice, we show exquisite accumulation of the fluor-tethered versions within breast tumors at very sensitive levels. Cell-based assays with the radiolabeled version showed picomolar detection in cells that express ectopic Hsp90. Our findings show that fluor-tethered or radiolabeled inhibitors targeting ectopic Hsp90 can be used to detect breast cancer malignancies through non-invasive imaging. PMID:24035283

  3. A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors.

    PubMed

    Santagata, Sara; Portella, Luigi; Napolitano, Maria; Greco, Adelaide; D'Alterio, Crescenzo; Barone, Maria Vittoria; Luciano, Antonio; Gramanzini, Matteo; Auletta, Luigi; Arra, Claudio; Zannetti, Antonella; Scala, Stefania

    2017-05-31

    C-X-C chemokine receptor 4 (CXCR4) is over-expressed in multiple human cancers and correlates with tumor aggressiveness, poor prognosis and increased risk for distant metastases. Imaging agents for CXCR4 are thus highly desirable. We developed a novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) conjugating the new developed CXCR4 peptidic antagonist Peptide R with the NIR fluorescent dye VivoTag-S750. Specific CXCR4 binding was obtained in cells overexpressing human CXCR4 (B16-hCXCR4 and human melanoma cells PES43), but not in CXCR4 low expressing cells (FB-1). Ex vivo evaluation demonstrated that PepR-NIR750 specifically detects B16-hCXCR4-derived subcutaneous tumors and lung metastases. Fluorescence Molecular Tomography (FMT) in vivo imaging was performed on mice carrying subcutaneous CHO and CHO-CXCR4 tumors. PepR-NIR750 accumulates only in CXCR4-positive expressing subcutaneous tumors. Additionally, an intense NIR fluorescence signal was detected in PES43-derived lung metastases of nude mice injected with PepR-NIR750 versus mice injected with VivoTag-S750. With a therapeutic intent, mice bearing PES43-derived lung metastases were treated with Peptide R. A the dramatic reduction in PES43-derived lung metastases was detected through a decrease of the PepR-NIR750 signal. PepR-NIR750 is a specific probe for non-invasive detection of human high CXCR4-expressing tumors and metastatic lesion and thus a valuable tool for cancer molecular imaging.

  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. Effects of nicotinamide and carbogen on oxygenation in human tumor xenografts measured with luminescense based fiber-optic probes.

    PubMed

    Bussink, J; Kaanders, J H; Strik, A M; van der Kogel, A J

    2000-10-01

    In head and neck cancer, addition of both carbogen breathing and nicotinamide to accelerated fractionated radiotherapy showed increased loco-regional control rates. An assay based on the measurement of changes in tumor pO(2) in response to oxygenation modification could be helpful for selecting patients for these new treatment approaches. The fiber-optic oxygen-sensing device, OxyLite, was used to measure changes in pO(2), at a single position in tumors, after treatment with nicotinamide and carbogen in three human xenograft tumor lines with different vascular architecture and hypoxic patterns. Pimonidazole was used as a marker of hypoxia and was analyzed with a digital image processing system. At the position of pO(2) measurement, half of the tumors showed a local increase in pO(2) after nicotinamide administration. Steep increases in pO(2) were measured in most tumors during carbogen breathing although the increase was less pronounced in tumor areas with a low pre-treatment pO(2). A trend towards a faster local response to carbogen breathing for nicotinamide pre-treated tumors was found in all three lines. There were significant differences in hypoxic fractions, based on pimonidazole binding, between the three tumor lines. There was no correlation between hypoxic marker binding and the response to carbogen breathing. Temporal changes in local pO(2) can be measured with the OxyLite. This system was used to quantitate the effects of oxygen modifying treatments. Rapid increases in pO(2) during carbogen breathing were observed in most tumor areas. The locally measured response to nicotinamide was smaller and more variable. Bio-reductive hypoxic cell marker binding in combination with OxyLite pO(2) determination gives spatial information about the distribution patterns of tumor hypoxia at the microscopic level together with the possibility to continuously measure changes in pO(2) in specific tumor areas.

  6. FITC-conjugated cyclic RGD peptides as fluorescent probes for staining integrin αvβ3/αvβ5 in tumor tissues.

    PubMed

    Zheng, Yumin; Ji, Shundong; Czerwinski, Andrzej; Valenzuela, Francisco; Pennington, Michael; Liu, Shuang

    2014-11-19

    This study sought to evaluate FITC-conjugated cyclic RGD peptides (FITC-RGD2, FITC-3P-RGD2, and FITC-Galacto-RGD2) as fluorescent probes for in vitro assays of integrin αvβ3/αvβ5 expression in tumor tissues. FITC-RGD2, FITC-3P-RGD2, and FITC-Galacto-RGD2 were prepared, and their integrin αvβ3/αvβ5 binding affinity was determined using the displacement assay against (125)I-echistatin bound to U87MG glioma cells. IC50 values of FITC-Galacto-RGD2, FITC-3P-RGD2, and FITC-RGD2 were calculated to be 28 ± 8, 32 ± 7, and 89 ± 17 nM, respectively. The integrin αvβ3/αvβ5 binding affinity followed a general trend: FITC-Galacto-RGD2 ∼ FITC-3P-RGD2 > FITC-RGD2. The xenografted tumor-bearing models were established by subcutaneous injection of 5 × 10(6) tumor cells into shoulder flank (U87MG, A549, HT29, and PC-3) or mammary fat pad (MDA-MB-435) of each athymic nude mouse. Three to six weeks after inoculation, the tumor size was 0.1-0.3 g. Tumors were harvested for integrin αvβ3/αvβ5 staining, as well as hematoxylin and eosin (H&E) staining. Six human carcinoma tissues (colon cancer, pancreatic cancer, lung adenocarcinoma, squamous cell lung cancer, gastric cancer, and esophageal cancer) were obtained from recently diagnosed cancer patients. Human carcinoma slides were deparaffinized in xylene, rehydrated with ethanol, and then used for integrin αvβ3/αvβ5 staining, as well as H&E staining. It was found that the tumor staining procedures with FITC-conjugated cyclic RGD peptides were much simpler than those with the fluorescence-labeled integrin αvβ3 antibodies. Since FITC-RGD2, FITC-3P-RGD2, and FITC-Galacto-RGD2 were able to co-localize with the fluorescence-labeled integrin β3 antibody, their tumor localization and tumor cell binding are integrin αvβ3-specific. Quantification of the fluorescent intensity in five xenografted tumors (U87MG, MDA-MB-435, A549, HT29, and PC-3) and six human carcinoma tissues revealed an excellent linear relationship

  7. Probing the Bi-directional Interaction Between Microglia and Gliomas in a Tumor Microenvironment on a Microdevice.

    PubMed

    Gu, Rui; Zhang, Xu; Zhang, Ge; Tao, Tingting; Yu, Haibo; Liu, Lianqing; Dou, Ying; Li, Aiping; Qin, Jianhua

    2017-02-24

    It has been proven that microglia are involved in both early and late stages of glioma progression and contribute substantially to the tumor mass of gliomas. Because no appropriate in vitro or in vivo investigative approach is available, the dynamic interaction between microglia and gliomas during tumor formation remains unclear. In this study, three types of microfluidic assay were developed to examine the outcomes of the dynamic interaction between microglia and gliomas. Co-migration assay and two-dimensional cell co-culture assay have been used to show that microglial BV-2 cells migrate toward C6 glioma cells and inhibit tumor growth during the early stage of tumorigenesis. However, in three-dimensional cell spheres (three-dimensional cell co-culture assay) that contain a large amount of glioma cells, mimicking the late stage of glioma growth, the phagocytosis of microglia was suppressed, which suggests that glioma cells could reeducate classically activated microglia into a tumor-promoting state at some point during tumor progression. Notably, we found that microglia could contribute to tumor invasion and acquisition of the epithelial-mesenchymal transition phenotype in the glioma microenvironment during the early stage and the late stage of tumor progression. In conclusion, we have developed a potential quantitative method for in vitro study of glioma immunity and provided evidence for the duality of glioma-associated microglia.

  8. 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.

  9. Comprehensive Screening of Gene Copy Number Aberrations in Formalin-Fixed, Paraffin-Embedded Solid Tumors Using Molecular Inversion Probe-Based Single-Nucleotide Polymorphism Array.

    PubMed

    Singh, Rajesh R; Mehrotra, Meenakshi; Chen, Hui; Almohammedsalim, Alaa A; Sahin, Ayesagul; Bosamra, Alex; Patel, Keyur P; Routbort, Mark J; Lu, Xinyan; Ronald, Abraham; Mishra, Bal Mukund; Virani, Shumaila; Medeiros, L Jeffrey; Luthra, Rajyalakshmi

    2016-09-01

    Gene copy number aberrations (CNAs) represent a major class of cancer-related genomic alterations that drive solid tumors. Comprehensive and sensitive detection of CNAs is challenging because of often low quality and quantity of DNA isolated from the formalin-fixed, paraffin-embedded (FFPE) solid tumor samples. Here, in a clinical molecular diagnostic laboratory, we tested the utility and validated a molecular inversion probe-based (MIP) array to routinely screen for CNAs in solid tumors. Using low-input FFPE DNA, the array detects genome-wide CNAs with a special focus on 900 cancer-related genes. A cohort of 76 solid tumors of various types and tumor cellularity (20% to 100%), and four cancer cell lines were used. These harbored CNAs in clinically important genes (ERBB2, EGFR, FGFR1, KRAS, MYC) as detected by orthogonal techniques like next-generation sequencing or fluorescence in situ hybridization. Results of the MIP array were concordant with results from orthogonal techniques, and also provided additional information regarding the allelic nature of the CNAs. Limit-of-detection and assay reproducibility studies showed a high degree of sensitivity and reproducibility of detection, respectively. FFPE compatibility, ability to detect CNAs with high sensitivity, accuracy, and provide valuable information such as loss of heterozygosity along with relatively short turnaround times makes the MIP array a desirable clinical platform for routine screening of solid tumors in a clinical laboratory. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  10. Application of in situ hybridization probes for MLH-1 and MSH-2 in tissue microarrays of paraffin-embedded malignant melanomas: correlation with immunohistochemistry and tumor stage.

    PubMed

    Korabiowska, Monika; Cordon-Cardo, Carlos; Jaenckel, Fredericke; Stachura, Jerzy; Fischer, Gösta; Brinck, Ulrich

    2004-12-01

    Defects in DNA mismatch-repair genes MLH1 and MSH2 reported primarily in hereditary nonpolyposis colorectal carcinoma are present in many sporadic tumors, including malignant melanomas. The main aim of this study was to investigate the expression of these genes in malignant melanomas in relation to tumor stage. An experiment was performed on paraffin-embedded tissue microarrays of malignant melanomas applying in situ hybridization with probes produced by our research group and immunohistochemical techniques. In situ hybridization demonstrated MLH1 expression in 45 of 59 melanomas and MSH2 expression in 51 of 59 melanomas. Immunohistochemistry detected MLH1 expression in 46 of 59 melanomas and MSH2 expression in 50 of 59 melanomas. Down-regulation of expression of both DNA mismatch repair genes in malignant melanomas was observed. The findings obtained by in situ hybridization and immunohistochemistry correlated significantly. Our study demonstrates the suitability of in situ hybridization with MLH1 and MSH2 probes for paraffin-embedded tissue. Tissue microarrays can be used successfully in both in situ hybridization and immunohistochemistry to analyze the expression of DNA mismatch-repair genes.

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

    PubMed

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

    2014-01-01

    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 CB2R 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 CB2R-targeted molecular imaging probe and evaluate the specificity of the probe using human tumor cells that naturally overexpress CB2R. To synthesize the CB2R-targeted probe (NIR760-Q), a conjugable CB2R 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 CB2R positive cancers and elucidating the role of CB2R in the regulation of disease progression.

  13. 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.

  14. 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

  15. 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.

  16. Probe-based quantitative PCR assay for detecting constitutional and somatic deletions in the NF1 gene: application to genetic testing and tumor analysis.

    PubMed

    Terribas, Ernest; Garcia-Linares, Carles; Lázaro, Conxi; Serra, Eduard

    2013-06-01

    About 5% of patients with neurofibromatosis type 1 (NF1) bear constitutional microdeletions that encompass NF1 (neurofibromin 1) and neighboring genes. These patients are characterized by the development of a high number of dermal neurofibromas (dNFs), mental retardation, and an increased risk of developing a malignant peripheral nerve sheath tumor (MPNST). Additionally, 10% of somatic second hits identified in dNFs are caused by deletions involving the NF1 gene. To detect constitutional and somatic deletions, we developed a probe-based quantitative PCR (qPCR) assay for interrogating the copy number status of 11 loci distributed along a 2.8-Mb region around the NF1 gene. We developed the qPCR assay with Universal ProbeLibrary technology (Roche) and designed a Microsoft Excel spreadsheet to analyze qPCR data for copy number calculations. The assay fulfilled the essential aspects of the MIQE (minimum information for publication of quantitative real-time PCR experiments) guidelines and used the qBase relative quantification framework for calculations. The assay was validated with a set of DNA samples with known constitutional or somatic NF1 deletions. The assay showed high diagnostic sensitivity and specificity and distinguished between Type-1, Type-2, and atypical constitutional microdeletions in 14 different samples. It also identified 16 different somatic deletions in dNFs. These results were confirmed by multiplex ligation-dependent probe amplification. The qPCR assay provides a methodology for detecting constitutional NF1 microdeletions that could be incorporated as an additional technique in a genetic-testing setting. It also permits the identification of somatic NF1 deletions in tissues with a high percentage of cells bearing 2 copies of the NF1 gene. © 2013 American Association for Clinical Chemistry.

  17. 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.

  18. 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

  19. A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

    NASA Astrophysics Data System (ADS)

    Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

    2016-11-01

    The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes–permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.

  20. A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

    PubMed Central

    Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

    2016-01-01

    The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes–permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research. PMID:27830712

  1. 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.

  2. Optical imaging of tumor microenvironment

    PubMed Central

    Wu, Yihan; Zhang, Wenjie; Li, Jinbo; Zhang, Yan

    2013-01-01

    Tumor microenvironment plays important roles in tumor development and metastasis. Features of the tumor microenvironment that are significantly different from normal tissues include acidity, hypoxia, overexpressed proteases and so on. Therefore, these features can serve as not only biomarkers for tumor diagnosis but also theraputic targets for tumor treatment. Imaging modalities such as optical, positron emission tomography (PET) and magnetic resonance imaging (MRI) have been intensively applied to investigate tumor microenvironment. Various imaging probes targeting pH, hypoxia and proteases in tumor microenvironment were thus well developed. In this review, we will focus on recent examples on fluorescent probes for optical imaging of tumor microenvironment. Construction of these fluorescent probes were based on characteristic feature of pH, hypoxia and proteases in tumor microenvironment. Strategies for development of these fluorescent probes and applications of these probes in optical imaging of tumor cells or tissues will be discussed in this review paper. PMID:23342297

  3. 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

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

    PubMed

    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

  5. Development of an autofluorescent probe for brain cancer: probe characterization thanks to phantom studies

    NASA Astrophysics Data System (ADS)

    Leh, B.; Charon, Y.; Duval, M.-A.; Lefebvre, F.; Linden, S.; Menard, L.; Siebert, R.

    2010-02-01

    Glioblastoma are brain tumors currently incurable, however, optimized treatment gives better prognosis and quality of life. In case of surgical treatment, there is still need to help surgeons to determine whether a tissue is tumorous or not. Within the framework of the design of a new autofluorescence probe for this issue, optically calibrated gel phantoms have been developed using "tumorous" inclusions in a "healthy" environment. Depending on "tumor" shape, size and localization, the sensitivity of the probe is evaluated. The probe sensitivity for fluorescence spectroscopy will be presented. The probe configuration is also taken into account and compared to simulated results.

  6. 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.

  7. 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.

  8. 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.

  9. Mechanical properties of the tumor stromal microenvironment probed in vitro and ex vivo by in situ-calibrated optical trap-based active microrheology

    PubMed Central

    Staunton, Jack R; Vieira, Wilfred; Fung, King Leung; Lake, Ross; Devine, Alexus; Tanner, Kandice

    2016-01-01

    One of the hallmarks of the malignant transformation of epithelial tissue is the modulation of stromal components of the microenvironment. In particular, aberrant extracellular matrix (ECM) remodeling and stiffening enhances tumor growth and survival and promotes metastasis. Type I collagen is one of the major ECM components. It serves as a scaffold protein in the stroma contributing to the tissue’s mechanical properties, imparting tensile strength and rigidity to tissues such as those of the skin, tendons, and lungs. Here we investigate the effects of intrinsic spatial heterogeneities due to fibrillar architecture, pore size and ligand density on the microscale and bulk mechanical properties of the ECM. Type I collagen hydrogels with topologies tuned by polymerization temperature and concentration to mimic physico-chemical properties of a normal tissue and tumor microenvironment were measured by in situ-calibrated Active Microrheology by Optical Trapping revealing significantly different microscale complex shear moduli at Hz-kHz frequencies and two orders of magnitude of strain amplitude that we compared to data from bulk rheology measurements. Access to higher frequencies enabled observation of transitions from elastic to viscous behavior that occur at ~200Hz to 2750Hz, which largely was dependent on tissue architecture well outside the dynamic range of instrument acquisition possible with SAOS bulk rheology. We determined that mouse melanoma tumors and human breast tumors displayed complex moduli ~5–1000 Pa, increasing with frequency and displaying a nonlinear stress-strain response. Thus, we show the feasibility of a mechanical biopsy in efforts to provide a diagnostic tool to aid in the design of therapeutics complementary to those based on standard histopathology. PMID:27752289

  10. Synthesis and evaluation of a (99m)Tc-MAMA-propyl-thymidine complex as a potential probe for in vivo visualization of tumor cell proliferation with SPECT.

    PubMed

    Celen, Sofie; de Groot, Tjibbe; Balzarini, Jan; Vunckx, Kathleen; Terwinghe, Christelle; Vermaelen, Peter; Van Berckelaer, Lizette; Vanbilloen, Hubert; Nuyts, Johan; Mortelmans, Luc; Verbruggen, Alfons; Bormans, Guy

    2007-04-01

    Cytosolic thymidine kinase (TK1) catalyzes phosphorylation of thymidine to its monophosphate. TK1 activity is closely related with DNA synthesis, and thymidine analogs derivatized with bulky carboranylalkyl groups at the N-3 position were reported to be good substrates for TK1. Accordingly, we have synthesized (99m)Tc-MAMA-propyl-thymidine and evaluated it as a potential tumor tracer. The bis(S-trityl)-protected MAMA-propyl-thymidine precursor (3-N-[S-trityl-2-mercaptoethyl]-N-[N'-(S-trityl-2-mercaptoethyl)amidoacetyl]-aminopropyl-thymidine) was prepared in three steps, and its structure was confirmed with (1)H NMR and mass spectrometry. Deprotection of the thiols and labeling with (99m)Tc were done in a two-step, one-pot procedure, yielding (99m)Tc-MAMA-propyl-thymidine, which was analyzed with high-performance liquid chromatography, radio-LC-MS analysis (ESI+) and electrophoresis, and its log P was determined. The biodistribution in normal mice was evaluated, and its biodistribution in a radiation-induced fibrosarcoma (RIF) tumor mouse was compared with that of 3'-deoxy-3'-[(18)F] fluorothymidine [(18)F]FLT. (99m)Tc-MAMA-propyl-thymidine was obtained with a radiochemical yield of 70%. Electrophoresis indicated that the complex is uncharged, and its log P was 1.0. The molecular ion mass of the Tc complex was 589 Da, which is compatible with the hypothesized N(2)S(2)-oxotechnetium structure. Tissue distribution showed fast clearance from plasma primarily by the hepatobiliary pathway. Whole-body planar imaging after injection of (99m)Tc-MAMA-propyl-thymidine in an RIF tumor-bearing mouse showed high uptake in the liver and the intestines. No uptake was observed in the tumor, in contrast to the clear uptake observed for [(18)F] FLT visualized with muPET. Although it has been reported that TK1 accepts large substituents at the N-3 position of the thymine ring, the results of this study show that (99m)Tc-MAMA-propyl-thymidine cannot be used as a single photon emission

  11. Synthesis and in vitro and in vivo evaluation of SiFA-tagged bombesin and RGD peptides as tumor imaging probes for positron emission tomography.

    PubMed

    Lindner, Simon; Michler, Christina; Leidner, Stephanie; Rensch, Christian; Wängler, Carmen; Schirrmacher, Ralf; Bartenstein, Peter; Wängler, Björn

    2014-04-16

    Gastrin-releasing-peptide (GRP)-receptors and αvβ3-integrins are widely discussed as potential target structures for oncological imaging with positron emission tomography (PET). Favored by the overexpression of receptors on the surface of tumor cells good imaging characteristics can be achieved with highly specific radiolabeled receptor ligands. PEGylated bombesin (PESIN) derivatives as specific GRP receptor ligands and RGD (one-letter codes for arginine-glycine-aspartic acid) peptides as specific αvβ3 binders were synthesized and tagged with a silicon-fluorine-acceptor (SiFA) moiety. The SiFA synthon allows for a fast and highly efficient isotopic exchange reaction at room temperature giving the [(18)F]fluoride labeled peptides in up to 62% radiochemical yields (d.c.) and ≥99% radiochemical purity in a total synthesis time of less than 20 min. Using nanomolar quantities of precursor high specific activities of up to 60 GBq μmol(-1) were obtained. To compensate the high lipophilicity of the SiFA moiety various hydrophilic structure modifications were introduced leading to significantly reduced logD values. Competitive displacement experiments with the PESIN derivatives showed a 32 to 6 nM affinity to the GRP receptor on PC3 cells, and with the RGD peptides a 7 to 3 μM affinity to the αvβ3 integrins on U87MG cells. All derivatives proved to be stable in human plasma over at least 120 min. Small animal PET measurements and biodistribution studies revealed an enhanced and specific accumulation of the RGD peptide (18)F-SiFA-LysMe3-γ-carboxy-d-Glu-RGD (17) in the tumor tissue of U87MG tumor-bearing mice of 5.3% ID/g whereas the PESIN derivatives showed a high liver uptake and only a low accumulation in the tumor tissue of PC3 xenografts. Stability studies with compound 17 provided further information on its metabolism in vivo. These results altogether demonstrate that the reduction of the overall lipophilicity of SiFA tagged RGD peptides is a promising

  12. Aqueous synthesis of type-II CdTe/CdSe core-shell quantum dots for fluorescent probe labeling tumor cells.

    PubMed

    Zeng, Ruosheng; Zhang, Tingting; Liu, Jincheng; Hu, Song; Wan, Qiang; Liu, Xuanming; Peng, Zhiwei; Zou, Bingsuo

    2009-03-04

    In this paper, we report a two-step aqueous synthesis of highly luminescent CdTe/CdSe core/shell quantum dots (QDs) via a simple method. The emission range of the CdTe/CdSe QDs can be tuned from 510 to 640 nm by controlling the thickness of the CdSe shell. Accordingly, the photoluminescence quantum yield (PL QY) of CdTe/CdSe QDs with an optimized thickness of the CdSe shell can reach up to 40%. The structures and compositions of the core/shell QDs were characterized by transmission electron microscopy, x-ray diffraction, and x-ray photoelectron spectroscopy experiments, and their formation mechanism is discussed. Furthermore, folate conjugated CdTe/CdSe QDs in Hela cells were assessed with a fluorescence microscope. The results show that folate conjugated CdTe/CdSe QDs could enter tumor cells efficiently.

  13. Optical imaging probes in oncology.

    PubMed

    Martelli, Cristina; Lo Dico, Alessia; Diceglie, Cecilia; Lucignani, Giovanni; Ottobrini, Luisa

    2016-07-26

    Cancer is a complex disease, characterized by alteration of different physiological molecular processes and cellular features. Keeping this in mind, the possibility of early identification and detection of specific tumor biomarkers by non-invasive approaches could improve early diagnosis and patient management.Different molecular imaging procedures provide powerful tools for detection and non-invasive characterization of oncological lesions. Clinical studies are mainly based on the use of computed tomography, nuclear-based imaging techniques and magnetic resonance imaging. Preclinical imaging in small animal models entails the use of dedicated instruments, and beyond the already cited imaging techniques, it includes also optical imaging studies. Optical imaging strategies are based on the use of luminescent or fluorescent reporter genes or injectable fluorescent or luminescent probes that provide the possibility to study tumor features even by means of fluorescence and luminescence imaging. Currently, most of these probes are used only in animal models, but the possibility of applying some of them also in the clinics is under evaluation.The importance of tumor imaging, the ease of use of optical imaging instruments, the commercial availability of a wide range of probes as well as the continuous description of newly developed probes, demonstrate the significance of these applications. The aim of this review is providing a complete description of the possible optical imaging procedures available for the non-invasive assessment of tumor features in oncological murine models. In particular, the characteristics of both commercially available and newly developed probes will be outlined and discussed.

  14. Optical imaging probes in oncology

    PubMed Central

    Martelli, Cristina; Dico, Alessia Lo; Diceglie, Cecilia; Lucignani, Giovanni; Ottobrini, Luisa

    2016-01-01

    Cancer is a complex disease, characterized by alteration of different physiological molecular processes and cellular features. Keeping this in mind, the possibility of early identification and detection of specific tumor biomarkers by non-invasive approaches could improve early diagnosis and patient management. Different molecular imaging procedures provide powerful tools for detection and non-invasive characterization of oncological lesions. Clinical studies are mainly based on the use of computed tomography, nuclear-based imaging techniques and magnetic resonance imaging. Preclinical imaging in small animal models entails the use of dedicated instruments, and beyond the already cited imaging techniques, it includes also optical imaging studies. Optical imaging strategies are based on the use of luminescent or fluorescent reporter genes or injectable fluorescent or luminescent probes that provide the possibility to study tumor features even by means of fluorescence and luminescence imaging. Currently, most of these probes are used only in animal models, but the possibility of applying some of them also in the clinics is under evaluation. The importance of tumor imaging, the ease of use of optical imaging instruments, the commercial availability of a wide range of probes as well as the continuous description of newly developed probes, demonstrate the significance of these applications. The aim of this review is providing a complete description of the possible optical imaging procedures available for the non-invasive assessment of tumor features in oncological murine models. In particular, the characteristics of both commercially available and newly developed probes will be outlined and discussed. PMID:27145373

  15. The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics.

    PubMed

    Meredith, Elizabeth J; Holder, Michelle J; Chamba, Anita; Challa, Anita; Drake-Lee, Adrian; Bunce, Christopher M; Drayson, Mark T; Pilkington, Geoffrey; Blakely, Randy D; Dyer, Martin J S; Barnes, Nicholas M; Gordon, John

    2005-07-01

    Following our previous description of the serotonin transporter (SERT) acting as a conduit to 5-hydroxytryptamine (5-HT)-mediated apoptosis, specifically in Burkitt's lymphoma, we now detail its expression among a broad spectrum of B cell malignancy, while exploring additional SERT substrates for potential therapeutic activity. SERT was readily detected in derived B cell lines with origins as diverse as B cell precursor acute lymphoblastic leukemia, mantle cell lymphoma, diffuse large B cell lymphoma, and multiple myeloma. Concentration and timecourse kinetics for the antiproliferative and proapoptotic activities of the amphetamine derivatives fenfluramine (an appetite suppressant) and 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") revealed them as being similar to the endogenous indoleamine. A tricyclic antidepressant, clomipramine, instead mirrored the behavior of the selective serotonin reuptake inhibitor fluoxetine, both being effective in the low micromolar range. A majority of neoplastic clones were sensitive to one or more of the serotonergic compounds. Dysregulated bcl-2 expression, either by t(14;18)(q32;q21) translocation or its introduction as a constitutively active transgene, provided protection from proapoptotic but not antiproliferative outcomes. These data indicate a potential for SERT as a novel anti-tumor target for amphetamine analogs, while evidence is presented that the seemingly more promising antidepressants are likely impacting malignant B cells independently of the transporter itself.

  16. Synthesis of AS1411-aptamer-conjugated CdTe quantum dots with high fluorescence strength for probe labeling tumor cells.

    PubMed

    Alibolandi, Mona; Abnous, Khalil; Ramezani, Mohammad; Hosseinkhani, Hossein; Hadizadeh, Farzin

    2014-09-01

    In this paper, we report microwave-assisted, one-stage synthesis of high-quality functionalized water-soluble cadmium telluride (CdTe) quantum dots (QDs). By selecting sodium tellurite as the Te source, cadmium chloride as the Cd source, mercaptosuccinic acid (MSA) as the capping agent, and a borate-acetic acid buffer solution with a pH range of 5-8, CdTe nanocrystals with four colors (blue to orange) were conveniently prepared at 100 °C under microwave irradiation in less than one hour (reaction time: 10-60 min). The influence of parameters such as the pH, Cd:Te molar ratio, and reaction time on the emission range and quantum yield percentage (QY%) was investigated. The structures and compositions of the prepared CdTe QDs were characterized by transmission electron microscopy, energy-dispersive X-ray spectroscopy, selective area electron diffraction, and X-ray powder diffraction experiments. The formation mechanism of the QDs is discussed in this paper. Furthermore, AS1141-aptamer-conjugated CdTe QDs in the U87MG glioblastoma cell line were assessed with a fluorescence microscope. The obtained results showed that the best conditions for obtaining a high QY of approximately 87% are a pH of 6, a Cd:Te molar ratio of 5:1, and a 30-min reaction time at 100 °C under microwave irradiation. The results showed that AS1141-aptamer-conjugated CdTe QDs could enter tumor cells efficiently. It could be concluded that a facile high-fluorescence-strength QD conjugated with a DNA aptamer, AS1411, which can recognize the extracellular matrix protein nucleolin, can specifically target U87MG human glioblastoma cells. The qualified AS1411-aptamer-conjugated QDs prepared in this study showed excellent capabilities as nanoprobes for cancer targeting and molecular imaging.

  17. Probing the infiltrating character of brain tumors: inhibition of RhoA/ROK-mediated CD44 cell surface shedding from glioma cells by the green tea catechin EGCg.

    PubMed

    Annabi, Borhane; Bouzeghrane, Mounia; Moumdjian, Robert; Moghrabi, Albert; Béliveau, Richard

    2005-08-01

    Glioma cell-surface binding to hyaluronan (HA), a major constituent of the brain extracellular matrix (ECM) environment, is regulated through a complex membrane type-1 matrix metalloproteinase (MT1-MMP)/CD44/caveolin interaction that takes place at the leading edges of invading cells. In the present study, intracellular transduction pathways required for the HA-mediated recognition by infiltrating glioma cells in brain was investigated. We show that the overexpression of the GTPase RhoA up-regulated MT1-MMP expression and triggered CD44 shedding from the U-87 glioma cell surface. This potential implication in cerebral metastatic processes was also observed in cells overexpressing the full-length recombinant MT1-MMP, while the overexpression of a cytoplasmic domain truncated from of MT1-MMP failed to do so. This suggests that the cytoplasmic domain of MT1-MMP transduces intracellular signaling leading to RhoA-mediated CD44 shedding. Treatment of glioma cells with the Rho-kinase (ROK) inhibitor Y27632, or with EGCg, a green tea catechin with anti-MMP and anti-angiogenesis activities, antagonized both RhoA- and MT1-MMP-induced CD44 shedding. Conversely, overexpression of recombinant ROK stimulated CD44 release. Taken together, our results suggest that RhoA/ROK intracellular signaling regulates MT1-MMP-mediated CD44 recognition of HA. These molecular processes may partly explain the diffuse brain-infiltrating character of glioma cells within the surrounding parenchyma and thus be a target for new approaches to anti-tumor therapy.

  18. 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.

  19. 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.

  20. 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

  1. Controlled assembly of two new bicapped bisupporting Keggin-polyoxometalate derivatives: [M(2,2'-bpy){sub 2}(H{sub 2}O)]{sub 2}[SiMo{sup VI}{sub 8}Mo{sup V}{sub 4}V{sup IV}{sub 2}O{sub 42}] (M=Co, Zn)

    SciTech Connect

    Shi Zhenyu; Gu Xiaojun; Peng Jun. E-mail: jpeng@nenu.edu.cn; Chen Yanhui

    2005-06-15

    Two new neutral bicapped bisupporting Keggin-polyoxometalate derivatives: [M(2,2'-bpy){sub 2}(H{sub 2}O)]{sub 2}[SiMo{sup VI}{sub 8}Mo{sup V}{sub 4}V{sup IV}{sub 2}O{sub 42}] (M=Co 1, Zn 2; 2,2'-bpy=2,2'-bipyridine), have been synthesized under hydrothermal conditions by directly using H{sub 4}SiMo{sub 12}O{sub 40} as starting materials. Crystal data for compound 1: C{sub 40}H{sub 36}Co{sub 2}Mo{sub 12}N{sub 8}O{sub 44}SiV{sub 2}, triclinic, space group P1-bar , a=11.884(2)A, b=12.459(3)A, c=12.652(3)A, {alpha}=71.02(3){sup o}, {beta}=74.51(3){sup o}, {gamma}=86.74(3){sup o}, V=1706.3(6)A{sup 3}, Z=1; for compound 2, C{sub 40}H{sub 36}Mo{sub 12}N{sub 8}O{sub 44}SiV{sub 2}Zn{sub 2}, triclinic, space group P1-bar , a=11.879(2)A, b=12.469(3)A, c=12.635(3)A, {alpha}=71.28(3){sup o}, {beta}=74.78(3){sup o}, {gamma}=86.60(3){sup o}, V=1709.6(6)A{sup 3}, Z=1. The studies of the electrochemical property of compounds 1 and 2 exhibit similar redox behavior to the parent [(C{sub 4}H{sub 9}){sub 4}N]{sub 4}SiMo{sub 12}O{sub 40}, undergoing three two-electron reversible reductions. Variable-temperature magnetic susceptibility measurement of compound 1 demonstrates the presence of antiferromagnetic interactions.

  2. 21 CFR 886.1670 - Ophthalmic isotope uptake probe.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., by a probe which is placed in close proximity to the eye, the uptake of a radioisotope (phosphorus 32) by tumors to detect tumor masses on, around, or within the eye. (b) Classification. Class II....

  3. 21 CFR 886.1670 - Ophthalmic isotope uptake probe.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., by a probe which is placed in close proximity to the eye, the uptake of a radioisotope (phosphorus 32) by tumors to detect tumor masses on, around, or within the eye. (b) Classification. Class II....

  4. 21 CFR 886.1670 - Ophthalmic isotope uptake probe.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., by a probe which is placed in close proximity to the eye, the uptake of a radioisotope (phosphorus 32) by tumors to detect tumor masses on, around, or within the eye. (b) Classification. Class II....

  5. 21 CFR 886.1670 - Ophthalmic isotope uptake probe.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., by a probe which is placed in close proximity to the eye, the uptake of a radioisotope (phosphorus 32) by tumors to detect tumor masses on, around, or within the eye. (b) Classification. Class II....

  6. 21 CFR 886.1670 - Ophthalmic isotope uptake probe.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., by a probe which is placed in close proximity to the eye, the uptake of a radioisotope (phosphorus 32) by tumors to detect tumor masses on, around, or within the eye. (b) Classification. Class II....

  7. 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.

  8. High efficiency diffusion molecular retention tumor targeting.

    PubMed

    Guo, Yanyan; Yuan, Hushan; Cho, Hoonsung; Kuruppu, Darshini; Jokivarsi, Kimmo; Agarwal, Aayush; Shah, Khalid; Josephson, Lee

    2013-01-01

    Here we introduce diffusion molecular retention (DMR) tumor targeting, a technique that employs PEG-fluorochrome shielded probes that, after a peritumoral (PT) injection, undergo slow vascular uptake and extensive interstitial diffusion, with tumor retention only through integrin molecular recognition. To demonstrate DMR, RGD (integrin binding) and RAD (control) probes were synthesized bearing DOTA (for (111) In(3+)), a NIR fluorochrome, and 5 kDa PEG that endows probes with a protein-like volume of 25 kDa and decreases non-specific interactions. With a GFP-BT-20 breast carcinoma model, tumor targeting by the DMR or i.v. methods was assessed by surface fluorescence, biodistribution of [(111)In] RGD and [(111)In] RAD probes, and whole animal SPECT. After a PT injection, both probes rapidly diffused through the normal and tumor interstitium, with retention of the RGD probe due to integrin interactions. With PT injection and the [(111)In] RGD probe, SPECT indicated a highly tumor specific uptake at 24 h post injection, with 352%ID/g tumor obtained by DMR (vs 4.14%ID/g by i.v.). The high efficiency molecular targeting of DMR employed low probe doses (e.g. 25 ng as RGD peptide), which minimizes toxicity risks and facilitates clinical translation. DMR applications include the delivery of fluorochromes for intraoperative tumor margin delineation, the delivery of radioisotopes (e.g. toxic, short range alpha emitters) for radiotherapy, or the delivery of photosensitizers to tumors accessible to light.

  9. 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,…

  10. 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,…

  11. 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.

  12. The diagnostic role of 99mTc-dual receptor targeted probe and targeted peptide bombesin (RGD-BBN) SPET/CT in the detection of malignant and benign breast tumors and axillary lymph nodes compared to ultrasound.

    PubMed

    Ji, Tiefeng; Sun, Yu; Chen, Bin; Ji, Bin; Gao, Shi; Ma, Qingjie; Cheng, Guanghui; Zhang, Haishan

    2015-01-01

    This study aimed to explore the diagnostic role of a new dual receptor-targeted probe, integrin ανβ3 and gastrin releasing peptide receptor (GRPR) targeted peptide Glu-c(RGDyK)-bombesin (RGD-BBN) labeled with technetium-99m ((99m)Tc-RGD-BBN), using single photon emission tomography/computed tomography (SPET/CT) in the detection of breast tumor in comparison to ultrasound (US). One hundred and twenty six female patients with suspicious breast lesions who had already been scheduled for biopsy or surgery were enrolled in this study. All patients had previously underwent breast US and (99m)Tc-RGD-BBN SPET/CT. The US findings were evaluated according to the breast imaging report and the data system (BI-RADS). Technetium-99m-RGD-BBN SPET/CT images were interpreted independently by two experienced nuclear medicine physicians. A final diagnosis was made by histopathology of the specimens. A total of 130 lesions, 77 malignant and 53 benign lesions were ascertained. One hundred and twelve breast lesions, 69 malignant and 43 benign lesions were above 10mm in diameter and 18 breast lesions (8 malignant lesions and 10 benign lesions) were below 10mm. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of (99m)Tc-RGD-BBN SPET/CT and US for breast lesions were 93.5% vs. 81.8% (P<0.05), 79.2% vs. 75.5% (P>0.05), 86.7% vs. 82.9% (P>0.05), 89.4% vs. 74.1% (P<0.05) and 87.7% vs. 79.2% (P>0.05). Technetium-99m-RGD-BBN SPET/CT detected all lesions ≥10mm and US only detected 57 (P<0.05). In malignant lesions <10mm, US was superior than (99m)Tc-RGD-BBN SPET/CT (75.0% vs. 37.5%, P<0.05). There was no significant difference between the two methods no matter the size of the benign lesions. The overall sensitivity and specificity of (99m)Tc-RGD-BBN SPET/CT and US for axillae lymph nodes were 87.5% vs. 71.9% (P<0.05) and 77.6% vs. 68.9% (P>0.05), respectively. For the metastatic lymph nodes of <10mm, the sensitivity of (99m

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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. 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.

  15. Miniature standoff Raman probe for neurosurgical applications

    NASA Astrophysics Data System (ADS)

    Stevens, Oliver A. C.; Hutchings, Joanne; Gray, William; Vincent, Rosa Louise; Day, John C.

    2016-08-01

    Removal of intrinsic brain tumors is a delicate process, where a high degree of specificity is required to remove all of the tumor tissue without damaging healthy brain. The accuracy of this process can be greatly enhanced by intraoperative guidance. Optical biopsies using Raman spectroscopy are a minimally invasive and lower-cost alternative to current guidance methods. A miniature Raman probe for performing optical biopsies of human brain tissue is presented. The probe allows sampling inside a conventional stereotactic brain biopsy system: a needle of length 200 mm and inner diameter of 1.8 mm. By employing a miniature stand-off Raman design, the probe removes the need for any additional components to be inserted into the brain. Additionally, the probe achieves a very low internal silica background while maintaining good collection of Raman signal. To illustrate this, the probe is compared with a Raman probe that uses a pair of optical fibers for collection. The miniature stand-off Raman probe is shown to collect a comparable number of Raman scattered photons, but the Raman signal to background ratio is improved by a factor of five at Raman shifts below ˜500 cm-1. The probe's suitability for use on tissue is demonstrated by discriminating between different types of healthy porcine brain tissue.

  16. Gamma-Ray Imaging Probes.

    NASA Astrophysics Data System (ADS)

    Wild, Walter James

    1988-12-01

    External nuclear medicine diagnostic imaging of early primary and metastatic lung cancer tumors is difficult due to the poor sensitivity and resolution of existing gamma cameras. Nonimaging counting detectors used for internal tumor detection give ambiguous results because distant background variations are difficult to discriminate from neighboring tumor sites. This suggests that an internal imaging nuclear medicine probe, particularly an esophageal probe, may be advantageously used to detect small tumors because of the ability to discriminate against background variations and the capability to get close to sites neighboring the esophagus. The design, theory of operation, preliminary bench tests, characterization of noise behavior and optimization of such an imaging probe is the central theme of this work. The central concept lies in the representation of the aperture shell by a sequence of binary digits. This, coupled with the mode of operation which is data encoding within an axial slice of space, leads to the fundamental imaging equation in which the coding operation is conveniently described by a circulant matrix operator. The coding/decoding process is a classic coded-aperture problem, and various estimators to achieve decoding are discussed. Some estimators require a priori information about the object (or object class) being imaged; the only unbiased estimator that does not impose this requirement is the simple inverse-matrix operator. The effects of noise on the estimate (or reconstruction) is discussed for general noise models and various codes/decoding operators. The choice of an optimal aperture for detector count times of clinical relevance is examined using a statistical class-separability formalism.

  17. Carcinoid Tumor

    MedlinePlus

    ... are here Home > Types of Cancer > Carcinoid Tumor Carcinoid Tumor This is Cancer.Net’s Guide to Carcinoid Tumor. Use the menu below to choose the ... social workers, and patient advocates. Cancer.Net Guide Carcinoid Tumor Introduction Statistics Medical Illustrations Risk Factors Symptoms ...

  18. In Vitro Mouse and Human Serum Stability of a Heterobivalent Dual-Target Probe That Has Strong Affinity to Gastrin-Releasing Peptide and Neuropeptide Y1 Receptors on Tumor Cells.

    PubMed

    Ghosh, Arijit; Raju, Natarajan; Tweedle, Michael; Kumar, Krishan

    2017-02-01

    Receptor-targeting radiolabeled molecular probes with high affinity and specificity are useful in studying and monitoring biological processes and responses. Dual- or multiple-targeting probes, using radiolabeled metal chelates conjugated to peptides, have potential advantages over single-targeting probes as they can recognize multiple targets leading to better sensitivity for imaging and radiotherapy when target heterogeneity is present. Two natural hormone peptide receptors, gastrin-releasing peptide (GRP) and Y1, are specifically interesting as their expression is upregulated in most breast and prostate cancers. One of our goals has been to develop a dual-target probe that can bind both GRP and Y1 receptors. Consequently, a heterobivalent dual-target probe, t-BBN/BVD15-DO3A (where a GRP targeting ligand J-G-Abz4-QWAVGHLM-NH2 and Y1 targeting ligand INP-K [ɛ-J-(α-DO3A-ɛ-DGa)-K] YRLRY-NH2 were coupled), that recognizes both GRP and Y1 receptors was synthesized, purified, and characterized in the past. Competitive displacement cell binding assay studies with the probe demonstrated strong affinity (IC50 values given in parentheses) for GRP receptors in T-47D cells (18 ± 0.7 nM) and for Y1 receptors in MCF7 cells (80 ± 11 nM). As a further evaluation of the heterobivalent dual-target probe t-BBN/BVD15-DO3A, the objective of this study was to determine its mouse and human serum stability at 37°C. The in vitro metabolic degradation of the dual-target probe in mouse and human serum was studied by using a (153)Gd-labeled t-BBN/BVD15-DO3A and a high-performance liquid chromatography/radioisotope detector analytical method. The half-life (t1/2) of degradation of the dual-target probe in mouse serum was calculated as 7 hours and only ∼20% degradation was seen after 6 hours incubation in human serum. The slow in vitro metabolic degradation of the dual-target probe can be compared with the degradation t1/2 of the corresponding monomeric probes, BVD15-DO3A

  19. Probe tip heating assembly

    SciTech Connect

    Schmitz, Roger William; Oh, Yunje

    2016-10-25

    A heating assembly configured for use in mechanical testing at a scale of microns or less. The heating assembly includes a probe tip assembly configured for coupling with a transducer of the mechanical testing system. The probe tip assembly includes a probe tip heater system having a heating element, a probe tip coupled with the probe tip heater system, and a heater socket assembly. The heater socket assembly, in one example, includes a yoke and a heater interface that form a socket within the heater socket assembly. The probe tip heater system, coupled with the probe tip, is slidably received and clamped within the socket.

  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. Mammary tumors

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Mammary neoplasia is one of the more common malignancies affecting domestic species. Despite their importance, they are often over- diagnosed, undertreated and subject to several misconceptions propagated by veterinarians and pet owners alike. Mammary neoplasia is the most frequent tumor type encountered in the female accounting for almost half of all malignancies reported. The canine has the highest incidence of mammary tumors of all domestic species. In the dog, about 65 percent of mammary tumors are benign mixed tumors, and 25 percent are carcinomas. The rest are adenomas, myoepitheliomas, and malignant mixed tumors. The age distribution of mammary tumors closely follows the age distribution of most tumors in the dog. Mammary tumors are rare in dogs 2 years old, but incidence begins to increase sharply at approximately 6 years of age. Median age at diagnosis is about 10 years. No breed predilection has been consistently reported.

  2. 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.

  3. Wilms Tumor

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Wilms Tumor KidsHealth > For Parents > Wilms Tumor Print A A A What's in this article? ... their child has cancer. Fortunately, most kids with Wilms tumor, a rare kidney cancer, survive and go on ...

  4. Tracheobronchial tumors

    PubMed Central

    Milenkovic, Branislava

    2016-01-01

    Tumors of trachea and bronchi are uncommon and can occur in the form of benign or low- and high-grade malignant tumors. Although tracheobronchial tumors (TBTs) represent only 0.6% of all pulmonary tumors, they are clinically significant. Delays in diagnosis of these tumors commonly occur because the signs and symptoms caused by these tumors are nonspecific and chest radiographs are often considered unremarkable. Therefore, novel radiological techniques and better access to flexible bronchoscopy enable detection of larger number of TBT. The purpose of this article is to provide a review of tracheal and bronchial tumors and discuss significant aspects of the different TBT with focus on clinical manifestations and diagnostic procedures. PMID:28066620

  5. In Vivo Interrogation of the Hypoxic Transcriptome of Solid Tumors: Optimizing Hypoxic Probe Labeling with Laser Capture Microdissection for Isolation of High-Quality RNA for Deep Sequencing Analysis.

    PubMed

    Brady, Lauren K; Popov, Vladimir; Koumenis, Constantinos

    2016-01-01

    Global gene expression analysis is a powerful method for identifying biological networks and regulatory mechanisms that govern cellular or tissue-level responses to physiologic stress. In the context of tumor biology, differential gene expression studies have provided information about the growth, aggressiveness, prognosis, and therapeutic response of tumors in patients. Scientists are using these valuable data to investigate pathways that can be targeted therapeutically with the goal of improving patient outcome. RNA sequencing enables nucleotide resolution of expression of whole transcriptomes, but arrives with a new set of challenges surrounding the management and analysis of large datasets. This chapter aims to review technical advancements to current methods for isolating high-quality RNA for sequencing studies directly from hypoxic tissues and introduces select widely used applications for gene expression analyses of next-generation sequencing data.

  6. 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.

  7. 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.

  8. 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.

  9. Hot-wire probe

    NASA Technical Reports Server (NTRS)

    Mikulla, V.

    1976-01-01

    High-temperature platinum probe measures turbulence and Reynolds shear stresses in high-temperature compressible flows. Probe does not vibrate at high velocities and does not react like strain gage on warmup.

  10. A Magnetoresistance Measuring Probe.

    DTIC Science & Technology

    The in line four point probe, commonly used for measuring the sheet resistance in a conductor, cannot measure the anisotropic ferromagnetic magnetoresistance. However, the addition of two contact points that are not collinear with the current contacts give the probe the ability to non-destructively measure the anistropic magnetoresistance. Keywords: Magnetoresistance; Anisotropic; Thin-Film; Permalloy; Four Point Probe; Anisotropic Resistance.

  11. 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.

  12. 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.

  13. Inhibition of tumor growth and metastasis by photoimmunotherapy targeting tumor-associated macrophage in a sorafenib-resistant tumor model.

    PubMed

    Zhang, Chenran; Gao, Liquan; Cai, Yuehong; Liu, Hao; Gao, Duo; Lai, Jianhao; Jia, Bing; Wang, Fan; Liu, Zhaofei

    2016-04-01

    Tumor-associated macrophages (TAMs) play essential roles in tumor invasion and metastasis, and contribute to drug resistance. Clinical evidence suggests that TAM levels are correlated with local tumor relapse, distant metastasis, and poor prognosis in patients. In this study, we synthesized a TAM-targeted probe (IRD-αCD206) by conjugating a monoclonal anti-CD206 antibody with a near-infrared phthalocyanine dye. We then investigated the potential application of the IRD-αCD206 probe to near-infrared fluorescence (NIRF) imaging and photoimmunotherapy (PIT) of tumors resistant to treatment with the kinase inhibitor sorafenib. Sorafenib treatment had no effect on tumor growth in a 4T1 mouse model of breast cancer, but induced M2 macrophage polarization in tumors. M2 macrophage recruitment by sorafenib-treated 4T1 tumors was noninvasively visualized by in vivo NIRF imaging of IRD-αCD206. Small-animal single-photon emission computed tomography (SPECT)/CT and intratumoral microdistribution analysis indicated TAM-specific localization of the IRD-αCD206 probe in 4T1 tumors after several rounds of sorafenib treatment. Upon light irradiation, IRD-αCD206 suppressed the growth of sorafenib-resistant tumors. In vivo CT imaging and ex vivo histological analysis confirmed the inhibition of lung metastasis in mice by IRD-αCD206 PIT. These results demonstrate the utility of the IRD-αCD206 probe for TAM-targeted diagnostic imaging and treatment of tumors that are resistant to conventional therapeutics.

  14. Pituitary Tumors

    MedlinePlus

    ... National Brain Tumor Society 55Chapel Street Suite 200 Newton MA Newton, MA 02458 questions@braintumor.org http://www.braintumor. ... National Brain Tumor Society 55Chapel Street Suite 200 Newton MA Newton, MA 02458 questions@braintumor.org http:// ...

  15. 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 ...

  16. Carcinoid Tumors

    MedlinePlus

    Carcinoid tumors are rare, slow-growing cancers. They usually start in the lining of the digestive tract or in the lungs. They grow ... trouble breathing. Surgery is the main treatment for carcinoid tumors. If they haven't spread to other parts of the body, surgery can cure the cancer.

  17. 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 , ...

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. [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.

  5. Vascular Tumors

    PubMed Central

    Sepulveda, Abel; Buchanan, Edward P.

    2014-01-01

    Vascular anomalies are divided into two main groups: tumors and malformations. Vascular tumors are a large and complex group of lesions, especially for clinicians with none or little experience in this field. In the past, these lesions caused a great deal of confusion because many appear analogous to the naked eye. Thankfully, recent advances in diagnostic techniques have helped the medical community to enhance our comprehension, accurately label, diagnose, and treat these lesions. In this article, we will review the most frequent vascular tumors and provide the reader with the tools to properly label, diagnose, and manage these complex lesions. PMID:25045329

  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. Bone tumor

    MedlinePlus

    ... primary bone tumors include: Chondrosarcoma Ewing sarcoma Fibrosarcoma Osteosarcomas Cancers that most often spread to the bone are cancers of the: Breast Kidney Lung Prostate Thyroid These forms of cancer usually affect ...

  8. Spinal tumor

    MedlinePlus

    ... Livingstone; 2014:chap 49. Read More Brain tumor - children Hodgkin lymphoma Metastasis Spinal cord trauma Review Date 8/15/2016 Updated by: Todd Gersten, MD, Hematology/Oncology, Florida Cancer Specialists & Research Institute, Wellington, FL. Review ...

  9. Wilms' Tumor

    MedlinePlus

    ... team and have training in child development, recreation, psychology or social work. If your child must remain ... conditions/wilms-tumor/basics/definition/CON-20043492 . Mayo Clinic Footer Legal Conditions and Terms Any use of ...

  10. Tumor Grade

    MedlinePlus

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... much of the tumor tissue has normal breast (milk) duct structures Nuclear grade : an evaluation of the ...

  11. Wilms tumor

    MedlinePlus

    ... a type of kidney cancer that occurs in children. Causes WT is the most common form of childhood kidney cancer. The exact cause of this tumor in most children is unknown. A missing iris of the eye ( ...

  12. Pituitary tumor

    MedlinePlus

    ... enough of its hormones. This condition is called hypopituitarism . The causes of pituitary tumors are unknown. Some ... Cyst Endocrine glands Gigantism Growth hormone test Hyperthyroidism Hypopituitarism Multiple endocrine neoplasia (MEN) I Prolactin blood test ...

  13. Multipressure and Temperature Probe

    NASA Technical Reports Server (NTRS)

    Raman, K. R.

    1982-01-01

    Aerodynamic probe is a small cylinder tube holding a network of tiny tubes leading to various ports. Six parameters are recorded simultaneously with little interference with aerodynamic flow. Two tubes connected by a hot-wire tungsten probe sense steady and fluctuating components of total and static pressures; the feedbacks from these tubes are input into differential-pressure sensors to measure fluctuating components of the pressures. Data are recorded by instruments at the back end of the probe.

  14. [Phyllodes tumors].

    PubMed

    Cabaret, V; Delobelle-Deroide, A; Vilain, M O

    1995-01-01

    A review of mammary phyllodes tumors is presented. Clinical, radiological and cytological features are treated, with special emphasis on the histopathological grading system and prognostic indicators. Other analytical methods are described: immunohistochemistry, hormonal receptors study, flow cytometry and electron microscopy. A large place is also given to differential diagnosis, clinical course, histogenesis and originality of some phyllodes tumors. The authors stress the importance of wide excision and the contribution of frozen sections in surgical treatment.

  15. 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

  16. 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.

  17. 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.

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

    PubMed

    Andrews, Russell J; Mah, Robert W

    2003-01-01

    Remote surgery requires automated sensors, effectors and sensor-effector communication. The NASA Smart Probe Project has focused on the sensor aspect. 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. 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. Real-time tissue identification is achievable. Potential applications, including probes incorporating nanoelectrode arrays, are presented. Copyright 2003 S. Karger AG, Basel

  19. Rotary probe traversing mechanism

    NASA Astrophysics Data System (ADS)

    Hokenson, Gustave J.

    1985-04-01

    A simple mechanical device is presented which allows a probe to scan a plane in space without translating the probe support. The mechanism relies on the rotation of two shafts, one of which rotates the probe through space and the other controls the probe offset from the axis of rotation. The characteristic width of the area swept out is four times the characteristic width of the device. A simple ratcheting gear allows adjacent planes to be scanned for the purpose of obtaining gradients. Computerized control of the shafts rotations also allows noncircular domains to be scanned.

  20. Transient internal probe

    NASA Astrophysics Data System (ADS)

    Jarboe, Thomas R.; Mattick, Arthur T.

    1993-12-01

    The Transient Internal Probe (TIP) diagnostic is a novel method for probing the interior of hot magnetic fusion plasmas that are inaccessible with ordinary stationary probes. A small probe of magneto-optic (Verdet) material is fired through a plasma at speeds of several km/sec, illuminated by a laser beam. The beam's polarization is rotated in the probe by the local magnetic field and retroreflection back to a polarimetry detector allows determination of the B-field profile across the diameter of a plasma at a spatial resolution of better than 1-cm and an absolute B-field resolution of a few tens of Gauss. The principal components of a TIP diagnostic system were developed and tested. A two-stage light gas gun was constructed that accelerates 30-caliber projectiles to 3 km/sec, and methods were examined for stripping a lexan sabot from a probe prior to entry into a plasma. Probes of CdMnTe and FR-5 Verdet glass were fabricated, and a polarimetry system was constructed for resolving polarization to within 0.25 deg. The diagnostic was validated by measuring a static B-field with a moving (dropped) TIP probe, and finding agreement with Hall-probe measurements to within experimental accuracy (40 Gauss).

  1. Rocket exhaust probe

    NASA Astrophysics Data System (ADS)

    Kessel, P. A.

    1986-01-01

    Disclosed is a rocket exhaust probe for collecting particulates from a rocket exhaust plume. The probe comprises a tungsten nose tip, a tip holder, a probe body, and a tail section. Rocket exhaust gas enters the probe at the nose tip inlet and passes into a mixing chamber where the exhaust gas mixes with an inert cooling gas that cools and decelerates the exhaust gas. The mixture of exhaust gas and inert gas then passes into a diffusion chamber where it further cools and decelerates before passsing through a submicron particle collection filter.

  2. 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

  3. Probing Skills for Tutors.

    ERIC Educational Resources Information Center

    Brown, Beryl E.

    The Office of Academic Support and Instructional Services (OASIS) at the University of California at San Diego sponsors a workshop that teaches tutors to use five types of probing skills. The use of the skills is fundamental to the student learner's acquisition of complex relationships and problem solving skills. The five types of probes are:…

  4. 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…

  5. 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…

  6. [Craniosinusonasal tumors].

    PubMed

    Blagoveshchenskaia, N S; Egorova, V K

    1997-01-01

    Tumors extending into the nasal cavity, cranium, and paranasal sinuses have a number of distinctive features to take into consideration. Among them are the communication with an open air, high incidence of associated intracranial infections, specific complications (i.e. suppurative sinusitis, polyps, mucocele, pneumocephalus, nasal CSF leak). The features mentioned make these lesions unique. 50 consecutive patients underwent treatment in Burdenko Neurosurgical Institute. The diagnosis was confirmed either by CT, MRI, or at operation. Rhinological and otoneurological signs were also subjected to analysis. Most frequently these tumors (the majority of which were meningiomas (n = 34) extended into the nasal cavity (40 patients) and paranasal sinuses (n = 50). It was noted that the clinical signs vary depending on the histological type of tumor, its location and direction of growth (i.e. medial or lateral). Medially growing tumors usually involved 2-4 sinuses, while laterally growing tumors involved only one sinus. Among the symptoms, disturbances of smell, conductive hearing impairment, deformation of both the soft and hard palate, slowing of the experimental nystagmus due to disturbed extraocular movements. Some light is shed on the differential diagnosis, indications for various surgical approaches (transcranial, transnasal, and facial). The results of surgical treatment and postoperative complications are presented in the paper. The diagnosis and treatment of such patients require an interdisciplinary approach while would involve a team of a neurosurgeon, neuroradiologist, otoneurologist, and a neuro-ophthalmologist.

  7. Spinal Cord Tumor

    MedlinePlus

    Spinal cord tumor Overview By Mayo Clinic Staff A spinal tumor is a growth that develops within your ... as vertebral tumors. Tumors that begin within the spinal cord itself are called spinal cord tumors. There are ...

  8. What Is Wilms Tumor?

    MedlinePlus

    ... Treatment? Wilms Tumor About Wilms Tumor What Is Wilms Tumor? Cancer starts when cells in the body begin ... live normal, healthy lives with just one kidney. Wilms tumors Wilms tumors are the most common cancers in ...

  9. 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

  10. Electron temperature probe

    NASA Astrophysics Data System (ADS)

    Oyama, K.-I.; Cheng, C. Z.

    2013-11-01

    The electron temperature probe (ETP) was invented in Japan in 1970's. The probe measures the electron temperature accurately and the measurement is not influenced by the electrode contamination. The instrument has low weight, low data transmission bit rate and low power consumption. The probe has been deployed in many sounding rockets, Earth orbiting scientific satellites, and Mars exploration spacecraft in Japan. The probe has also been deployed in sounding rockets in West Germany, India, Canada, USA, and Brazil. The probe has also been deployed in Brazilian satellites, Korean satellites, and recently as a Taiwan satellite payload. The manuscript describes the principle of the ETP instrument, the system configuration, the mechanical interface with respect to the sensor location, the control timing between data processing units; some useful information, the interference with other instruments, and future improvements and tasks. Some useful information for conducting performance check after the instrument fabrication and before the flight deployment is also presented in Appendix A.

  11. Circumferential pressure probe

    NASA Technical Reports Server (NTRS)

    Holmes, Harlan K. (Inventor); Moore, Thomas C. (Inventor); Fantl, Andrew J. (Inventor)

    1989-01-01

    A probe for measuring circumferential pressure inside a body cavity is disclosed. In the preferred embodiment, a urodynamic pressure measurement probe for evaluating human urinary sphincter function is disclosed. Along the length of the probe are disposed a multiplicity of deformable wall sensors which typically comprise support tube sections with flexible side wall areas. These are arranged along the length of the probe in two areas, one just proximal to the tip for the sensing of fluid pressure inside the bladder, and five in the sensing section which is positioned within the urethra at the point at which the urinary sphincter constricts to control the flow of urine. The remainder of the length of the probe comprises multiple rigid support tube sections interspersed with flexible support tube sections in the form of bellows to provide flexibility.

  12. 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.

  13. 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.

  14. DNA Probe Pooling for Rapid Delineation of Chromosomal Breakpoints

    PubMed Central

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

    2009-01-01

    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 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 multiclone and multicolor 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 3 to 4 days. (J Histochem Cytochem 57:587–597, 2009) PMID:19223294

  15. Application of probe manipulator to repair probe cards

    NASA Astrophysics Data System (ADS)

    Konno, Takeshi; Kobayashi, Mikihiko; Egashira, Mitsuru; Machida, Kazumichi; Urata, Atsuo

    2006-03-01

    We fabricated an apparatus for manipulation and welding of fine metal objects using a probe. The apparatus is composed of a work probe of a tungsten alloy needle, stages, a DC power supply, and an observation system. The work probe is held vertically above a gold substrate placed on stages to control the relative position against the work probe. The DC power supply is equipped to apply voltage of 0-10kV between the work probe and the substrate. One application of the apparatus is to repair probe cards. Thousands of contact probes (needles) are mounted on the printed circuit board (PCB) in the probe card. The contact probes are mounted one by one by the hands. Recently, an array of the contact probe on the PCB is produced by the LIGA process in response to narrower semiconductor pitch length. The problem is that there are no methods to repair a wrong contact probe. Whole of the contact probes should be a waste owing to one wrong contact probe. We propose to replace a wrong contact probe with a good one using our apparatus. Experiments to remove a contact probe by the apparatus is carried out using the specimen of a mimic probe card, where a cantilever type contact probes are arranged with a pitch of 25 micrometers. Removal of the wrong contact probe is carried out by a non-contact discharge and a contact discharge using the apparatus. High voltage of about 1-2kV is applied after the work probe is moved to above the target contact probe for the non-contact discharge. While high voltage of about10kV is applied after the work probe is positioned in contact with the target contact probe for the contact discharge. The target contact probe is removed by both methods, though the neighboring contact probes are damaged. The latter method is hopeful for removal for repair of the probe card.

  16. Radionuclide imaging of tumor angiogenesis.

    PubMed

    Dijkgraaf, Ingrid; Boerman, Otto C

    2009-12-01

    Angiogenesis is a multistep process regulated by pro- and antiangiogenic factors. In order to grow and metastasize, tumors need a constant supply of oxygen and nutrients. For growth beyond 1-2 mm in size, tumors are dependent on angiogenesis. Inhibition of angiogenesis is a new cancer treatment strategy that is now widely investigated clinically. Researchers have begun to search for objective measures that indicate pharmacologic responses to antiangiogenic drugs. Therefore, there is a great interest in techniques to visualize angiogenesis in growing tumors noninvasively. Several markers have been described that are preferentially expressed on newly formed blood vessels in tumors (alpha(v)beta(3) integrin, vascular endothelial growth factor, and its receptor, prostate-specific membrane antigen) and in the extracellular matrix surrounding newly formed blood vessels (extra domain B of fibronectin, Tenascin-C, matrix metalloproteinases, and Robo-4). Several ligands targeting these markers have been tested as a radiotracer for imaging angiogenesis in tumors. The potential of some of these tracers, such as radiolabeled cyclic RGD peptides and radiolabeled anti-PSMA antibodies, has already been tested in cancer patients, while for markers such as Robo-4, the ligand has not yet been identified. In this review, an overview on the currently used nuclear imaging probes for noninvasive visualization of tumor angiogenesis is given.

  17. Pioneer Jupiter orbiter probe mission 1980, probe description

    NASA Technical Reports Server (NTRS)

    Defrees, R. E.

    1974-01-01

    The adaptation of the Saturn-Uranus Atmospheric Entry Probe (SUAEP) to a Jupiter entry probe is summarized. This report is extracted from a comprehensive study of Jovian missions, atmospheric model definitions and probe subsystem alternatives.

  18. [Gastric tumors and tumor precursors].

    PubMed

    Röcken, C

    2017-03-01

    Gastric cancer is the fifth (men) and sixth (women) most common cause of cancer-related death in Germany. Despite a declining incidence of distal gastric cancer, the prognosis remains dismal: the 5‑year survival rate ranges between 35% for women and 31% for men. The majority are adenocarcinomas, which occur sporadically, familial or hereditary. Adenomas and intraepithelial neoplasms are considered as precursor lesions. Recently, whole genome sequencing and comprehensive molecular profiling described four molecular subtypes of gastric cancer: Epstein-Barr virus (EBV) positive, microsatellite unstable, chromosomal unstable and genomically stable gastric cancer. Currently, only the TNM classification has stood the test of time for the assessment of patient prognosis. Neuroendocrine tumor types 1-3 and soft tissue tumors occur significantly less often in the stomach. Gastrointestinal stromal tumors and inflammatory fibroid polyps are among the more common soft tissue tumors of the stomach and show distinct phenotypes. This review gives an overview of the current World Health Organization (WHO) classification of gastric tumors.

  19. 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

  20. Fluorescent carbohydrate probes for cell lectins

    NASA Astrophysics Data System (ADS)

    Galanina, Oxana; Feofanov, Alexei; Tuzikov, Alexander B.; Rapoport, Evgenia; Crocker, Paul R.; Grichine, Alexei; Egret-Charlier, Marguerite; Vigny, Paul; Le Pendu, Jacques; Bovin, Nicolai V.

    2001-09-01

    Fluorescein labeled carbohydrate (Glyc) probes were synthesized as analytical tools for the study of cellular lectins, i.e. SiaLe x-PAA-flu, Sia 2-PAA-flu, GlcNAc 2-PAA-flu, LacNAc-PAA-flu and a number of similar ones, with PAA a soluble polyacrylamide carrier. The binding of SiaLe x-PAA-flu was assessed using CHO cells transfected with E-selectin, and the binding of Sia 2-PAA-flu was assessed by COS cells transfected with siglec-9. In flow cytometry assays, the fluorescein probes demonstrated a specific binding to the lectin-transfected cells that was inhibited by unlabeled carbohydrate ligands. The intense binding of SiaLe x-PAA- 3H to the E-selectin transfected cells and the lack of binding to both native and permeabilized control cells lead to the conclusion that the polyacrylamide carrier itself and the spacer arm connecting the carbohydrate moiety with PAA did not contribute anymore to the binding. Tumors were obtained from nude mice by injection of CHO E-selectin or mock transfected cells. The fluorescent SiaLe x-PAA-flu probe could bind to the tumor sections from E-selectin positive CHO cells, but not from the control ones. Thus, these probes can be used to reveal specifically the carbohydrate binding sites on cells in culture as well as cells in tissue sections. The use of the confocal spectral imaging technique with Glyc-PAA-flu probes offered the unique possibility to detect lectins in different cells, even when the level of lectin expression was rather low. The confocal mode of spectrum recording provided an analysis of the probe localization with 3D submicron resolution. The spectral analysis (as a constituent part of the confocal spectral imaging technique) enabled interfering signals of the probe and intrinsic cellular fluorescence to be accurately separated, the distribution of the probe to be revealed and its local concentration to be measured.

  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. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Characteristics of magnetic probes for identifying sentinel lymph nodes.

    PubMed

    Ookubo, Tetsu; Inoue, Yusuke; Kim, Dongmin; Ohsaki, Hiroyuki; Mashiko, Yusuke; Kusakabe, Moriaki; Sekino, Masaki

    2013-01-01

    The identification of the sentinel lymph nodes that cause tumor metastasis is important in breast cancer therapy. The detection of magnetic fluid accumulating in the lymph nodes using a magnetic probe allows surgeons to identify the lymph nodes. In this study, we carried out numerical simulations and experiments to investigate the sensitivity and basic characteristics of a magnetic probe consisting of a permanent magnet and a small magnetic sensor. The measured magnetic flux density arising from the magnetic fluid agreed well with the numerical results. In addition, the results helped realize an appropriate probe configuration for achieving high sensitivity to magnetic fluid. A prototype probe detected magnetic fluid located 30 mm from the probe head.

  7. Jupiter probe heatshield configuration optimization

    NASA Technical Reports Server (NTRS)

    Dirling, R. B., Jr.; Binder, J. D.

    1978-01-01

    The effect of initial probe heatshield shape on the total probe mass loss during Jovian entry is considered. Modification of the aerothermal environment and probe entry trajectory due to changing probe heatshield shape is included in a computerized technique designed for rapid assessment of the effect of probe initial shape on heatshield mass loss. Results obtained indicate the importance of trajectory and heating distribution coupling with probe shape and mass change.

  8. 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.

  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. Geological assessment probe

    NASA Astrophysics Data System (ADS)

    Collins, E. R.

    1980-04-01

    A probe is described which can be installed in a side hole that extends from a bore hole in the Earth, to assess the permeability of the strata surrounding the borehole. The probe is elongated and has a plurality of seals spaced therealong and sealed to the walls of the side hole to form a plurality of chambers sealed from one another. A tracer fluid injector on the probe can inject a tracer fluid into one of the chambers, while a tracer fluid detector located in another chamber can detect the tracer fluid, to thereby sense the permeability of the strata surrounding the side hole. The probe can include a train of modules, with each module having an inflatable packer which is inflated by the difference between the borehole pressure and the strata pressure.

  11. 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.

  12. Cryogenic Optoelectronic Probe Station

    DTIC Science & Technology

    2012-08-01

    capability is very important for a few on- going projects under DOD support. Selected Examples of Research Using COPS Example 1: sheet resistance measurement...donor concentration of this thin film contact material, we need to know the sheet resistance . As shown in Fig. 1, four electric probes are landed...voltage of 62.4 mV across probe 2 and 3. Therefore we can determine the sheet resistance by using Eq: = ( ) . This gives the sheet

  13. Outer planets probe testing

    NASA Technical Reports Server (NTRS)

    Smittkamp, J. A.; Grote, M. G.; Edwards, T. M.

    1977-01-01

    An atmospheric entry Probe is being developed by NASA Ames Research Center (ARC) to conduct in situ scientific investigations of the outer planets' atmospheres. A full scale engineering model of an MDAC-E Probe configuration, was fabricated by NASA ARC. Proof-of-concept test validation of the structural and thermal design is being obtained at NASA ARC. The model was successfully tested for shock and dynamic loading and is currently in thermal vacuum testing.

  14. Adjustable Pitot Probe

    NASA Technical Reports Server (NTRS)

    Ashby, George C., Jr.; Robbins, W. Eugene; Horsley, Lewis A.

    1991-01-01

    Probe readily positionable in core of uniform flow in hypersonic wind tunnel. Formed of pair of mating cylindrical housings: transducer housing and pitot-tube housing. Pitot tube supported by adjustable wedge fairing attached to top of pitot-tube housing with semicircular foot. Probe adjusted both radially and circumferentially. In addition, pressure-sensing transducer cooled internally by water or other cooling fluid passing through annulus of cooling system.

  15. "Cancer tumor".

    NASA Astrophysics Data System (ADS)

    Bronshtehn, V. A.

    The title is a phrase borrowed from a speech by a Leningrad pressman, V. E. Lvov, who called upon those attending a theoretical conference on ideological issues in astronomy held by the Leningrad Branch of the All-Union Astronomic and Geodetic Society (13 - 4 December 1948), "to make a more radical emphasis on the negative role of relativistic cosmology which is a cancer tumor disintegrating the contemporary astronomy theory, and a major ideological enemy of a materialist astronomy".

  16. 31P NMR spectroscopy of in vivo tumors

    NASA Astrophysics Data System (ADS)

    Ng, T. C.; Evanochko, W. T.; Hiramoto, R. N.; Ghanta, V. K.; Lilly, M. B.; Lawson, A. J.; Corbett, T. H.; Durant, J. R.; Glickson, J. D.

    A probe, suitable for any wide-bore NMR spectrometer, was constructed for monitoring high-resolution spectra of in vivo subcutaneously implanted tumors in mice. Preliminary studies of a variety of murine tumors (MOPC 104E myeloma, Dunn osteosarcoma, colon-26, ovarian M5, and mammary adenocarcinoma as well as human colon, mammary, and lung tumors in athymic mice) indicate that the 31P NMR spectrum is a sensitive monitor of progressive metabolic changes that occur during untreated tumor growth and an early indicator of tumor response to chemotherapy, hyperthermia, and X radiation. Response to each of these therapeutic modalities is accompanied by distinctly different spectral changes.

  17. Infrared spectroscopic imaging of renal tumor tissue

    NASA Astrophysics Data System (ADS)

    Šablinskas, Valdas; Urbonienė, Vidita; Ceponkus, Justinas; Laurinavicius, Arvydas; Dasevicius, Darius; Jankevičius, Feliksas; Hendrixson, Vaiva; Koch, Edmund; Steiner, Gerald

    2011-09-01

    Fourier transform infrared (FTIR) spectroscopic imaging has been used to probe the biochemical composition of human renal tumor tissue and adjacent normal tissue. Freshly resected renal tumor tissue from surgery was prepared as a thin cryosection and examined by FTIR spectroscopic imaging. Tissue types could be discriminated by utilizing a combination of fuzzy k-means cluster analysis and a supervised classification algorithm based on a linear discriminant analysis. The spectral classification is compared and contrasted with the histological stained image. It is further shown that renal tumor cells have spread in adjacent normal tissue. This study demonstrates that FTIR spectroscopic imaging can potentially serve as a fast and objective approach for discrimination of renal tumor tissue from normal tissue and even in the detection of tumor infiltration in adjacent tissue.

  18. Nuclear probes and intraoperative gamma cameras.

    PubMed

    Heller, Sherman; Zanzonico, Pat

    2011-05-01

    Gamma probes are now an important, well-established technology in the management of cancer, particularly in the detection of sentinel lymph nodes. Intraoperative sentinel lymph node as well as tumor detection may be improved under some circumstances by the use of beta (negatron or positron), rather than gamma detection, because the very short range (∼ 1 mm or less) of such particulate radiations eliminates the contribution of confounding counts from activity other than in the immediate vicinity of the detector. This has led to the development of intraoperative beta probes. Gamma camera imaging also benefits from short source-to-detector distances and minimal overlying tissue, and intraoperative small field-of-view gamma cameras have therefore been developed as well. Radiation detectors for intraoperative probes can generally be characterized as either scintillation or ionization detectors. Scintillators used in scintillation-detector probes include thallium-doped sodium iodide, thallium- and sodium-doped cesium iodide, and cerium-doped lutecium orthooxysilicate. Alternatives to inorganic scintillators are plastic scintillators, solutions of organic scintillation compounds dissolved in an organic solvent that is subsequently polymerized to form a solid. Their combined high counting efficiency for beta particles and low counting efficiency for 511-keV annihilation γ-rays make plastic scintillators well-suited as intraoperative beta probes in general and positron probes in particular Semiconductors used in ionization-detector probes include cadmium telluride, cadmium zinc telluride, and mercuric iodide. Clinical studies directly comparing scintillation and semiconductor intraoperative probes have not provided a clear choice between scintillation and ionization detector-based probes. The earliest small field-of-view intraoperative gamma camera systems were hand-held devices having fields of view of only 1.5-2.5 cm in diameter that used conventional thallium

  19. Huygens probe on target

    NASA Astrophysics Data System (ADS)

    1995-07-01

    In October 1997, a Titan/Centaur rocket lifting-off from Cape Canaveral will boost the spacecraft into a 6.7 year trajectory to reach Saturn. The trajectory will use two swing-bys of Venus in April 1998 and June 1999, followed by an Earth swing-by in August 1999 and a Jupiter swing-by in December 2000 to boost speed and reach Saturn in July 2004. A few months after going into orbit around Saturn, the Cassini spacecraft will release the Huygens probe for its descent through the atmosphere of Titan, the largest satellite of Saturn. The Huygens probe will measure the abundance of elements and compounds in Titan's atmosphere, the distribution of trace gases and aerosols, winds, temperature, pressure and surface state and its composition. A multi-spectral camera on the probe will provide images of the landscape of Titan. Titan is a unique planetary body in the solar system. It has an atmosphere which is primarily nitrogen. but is also rich in hydrocarbons. Due to the vast distance of the Saturnian system from the Sun, this atmosphere is at a very low temperature, thus greatly slowing down all the chemical processes. A study of this atmosphere will throw light on the development of our own atmosphere and contribute to our understanding of the origins of life on Earth. The Huygens probe is being developed by ESA with Aerospatiale (F) as the industrial prime contractor. Since the start of the programme in April 1990, very good progress has been made in design and hardware development. The entry into the Titan atmosphere will result in a very high surface temperature on the probe, generated as it decelerates due to the friction of the upper atmospheric layers. After the probe has slowed down sufficiently, a system of parachutes ensures a slow descent to the surface of Titan in approximately two and a half hours. The scientific measurements can only begin after the heat shield, which is needed to protect the probe during the high temperature entry phase, has been ejected

  20. Metastatic brain tumor

    MedlinePlus

    Brain tumor - metastatic (secondary); Cancer - brain tumor (metastatic) ... For many people with metastatic brain tumors, the cancer is not curable. It will eventually spread to other areas of the body. Prognosis depends on the type of tumor and ...

  1. Adrenal Gland Tumors: Statistics

    MedlinePlus

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  2. 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 ...

  3. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  4. 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 ...

  5. 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.

  6. Titan atmospheric probe

    NASA Astrophysics Data System (ADS)

    Swenson, B. L.

    1984-08-01

    Increased scientific interest in the structure and composition of Titan's atmosphere, clouds and surface have led to the study of mission options to the Saturnian system with the main goal of placing a probe into the atmosphere of the satellite. Two probe concepts have been studied by NASA: the first concept, a slightly modified Galileo probe capable of withstanding approximately 50 earth G during atmospheric entry heating and deceleration, would consist of a blunted 53 degree, 136-cm-diameter half-angle cone with a hemispherical afterbody, and a descent module containing scientific instruments and a parachute; the second concept, a system designed to provide in situ atmospheric measurements of Titan's organic haze layer, would consist of a probe using a 165-cm deployable graphite fabric decelerator, a 50-cm-diameter cylindrical descent module containing five instruments and a 2.5 m-diameter parachute and a 50-cm-radius spherical nose cap. Although the modified Galileo probe is feasible, its scientific drawback includes its inability to obtain in situ measurements above approximately 100 km.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Pressure measuring probe

    NASA Technical Reports Server (NTRS)

    Ashby, George C., Jr. (Inventor)

    1988-01-01

    The invention is a probe for measuring changes in pressure in a high velocity fluid stream over and adjacent to the surface of an object. The probe is formed of an exterior housing having a closed pressure chamber in which a piezoelectric pressure transducer is mounted. An open connector tube having a probe tip passes a portion of the fluid stream into the closed pressure chamber; any change of pressure within, which requires a settling-time to appear in the closed pressure chamber, is inversely proportional to the cross-sectional area of the connector tube. A cooling chamber formed around the pressure chamber is connected to a source of cooling fluid by means of inlet and outlet tubes.

  12. 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.

  13. Multispectral imaging probe

    SciTech Connect

    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.

  14. Multispectral imaging probe

    SciTech Connect

    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.

  15. Probing Tumor Microenvironment With In Vivo Phage Display

    DTIC Science & Technology

    2014-10-01

    Kazuki Sugahara CONTRACTING ORGANIZATION: Sanford-Burnham Medical Research Institute La Jolla, CA 92037-1005 REPORT DATE: October 2014 TYPE OF... REPORT : Final PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for...Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the

  16. Probing Tumor Microenvironment with In Vivo Phage Display

    DTIC Science & Technology

    2014-09-01

    Erkki Ruoslahti CONTRACTING ORGANIZATION: Sanford Burnham Medical Research Institute La Jolla, CA 92037 REPORT DATE: September 2014 TYPE OF REPORT ...Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the...reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215

  17. Evaluating tumor angiogenesis.

    PubMed

    Uh, Minji K; Kandel, Jessica; Kitajewski, Jan

    2013-01-01

    The evaluation of tumor angiogenesis in pancreatic cancers involves determining the status of tumor vasculature and hypoxia in the tumor. Describing the nature and extent of tumor angiogenesis involves evaluating the expression of endothelial and perivascular cells within the tumor, and the expression of angiogenesis-related genes in tumor vasculature. Here we describe the methodology for assessment of tumor vasculature in murine mouse models of cancer. Specifically, we provide methodology for the evaluation of tumor hypoxia, tumor vessel perfusion, and chromogenic and fluorescent immunohistochemistry applied to tumor vascular analysis.

  18. In Vivo Imaging of Mouse Tumors by a Lipidated Cathepsin S Substrate**

    PubMed Central

    Hu, Hai-Yu; Vats, Divya; Vizovisek, Matej; Kramer, Lovro; Germanier, Catherine; Wendt, K Ulrich; Rudin, Markus; Turk, Boris; Plettenburg, Oliver; Schultz, Carsten

    2014-01-01

    The synthesis and evaluation of two cathepsin S-specific probes is described. For long-term retention of the probe at the target site and a high signal-to-noise ratio, we introduced a lipidation approach via the simple attachment of palmitoic acid to the reporter. After cathepsin S-specific cleavage in cultured cells and in a grafted tumor mouse model, fluorescence increased owing to dequenching and we observed an intracellular accumulation of the fluorescence in the target tissue. The lipidated probe provided a prolonged and strongly fluorescent signal in tumors when compared to the very similar non-lipidated probe, demonstrating that non-invasive tumor identification is feasable. The homing principle by probe lipidation might also work for selective administration of cytotoxic compounds to specifically reduce tumor mass. PMID:24888522

  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. Endocavity Ultrasound Probe Manipulators.

    PubMed

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

    2013-06-01

    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.

  1. 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.

  2. 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.

  3. 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.

  4. Cervical Neoplasia Probe Control

    SciTech Connect

    Vargo, Timothy D.

    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)

  5. 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

  6. 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)

  7. 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…

  8. Tumor-Targeted Multimodal Optical Imaging with Versatile Cadmium-Free Quantum Dots

    PubMed Central

    Liu, Xiangyou; Braun, Gary B.; Zhong, Haizheng; Hall, David J.; Han, Wenlong; Qin, Mingde; Zhao, Chuanzhen; Wang, Meina; She, Zhi-Gang; Cao, Chuanbao; Sailor, Michael J.; Stallcup, William B.; Ruoslahti, Erkki

    2016-01-01

    The rapid development of fluorescence imaging technologies requires concurrent improvements in the performance of fluorescent probes. Quantum dots have been extensively used as an imaging probe in various research areas because of their inherent advantages based on unique optical and electronic properties. However, their clinical translation has been limited by the potential toxicity especially from cadmium. Here, a versatile bioimaging probe is developed by using highly luminescent cadmium-free CuInSe2/ZnS core/shell quantum dots conjugated with CGKRK (Cys–Gly–Lys–Arg–Lys) tumor-targeting peptides. This probe exhibits excellent photostability, reasonably long circulation time, minimal toxicity, and strong tumor-specific homing property. The most important feature of this probe is that it shows distinctive versatility in tumor-targeted multimodal imaging including near-infrared, time-gated, and two-photon imaging in different tumor models. In a glioblastoma mouse model, the targeted probe clearly denotes tumor boundaries and positively labels a population of diffusely infiltrating tumor cells, suggesting its utility in precise tumor detection during surgery. This work lays a foundation for potential clinical translation of the probe. PMID:27441036

  9. Mechanosensitive membrane probes.

    PubMed

    Dal Molin, Marta; Verolet, Quentin; Soleimanpour, Saeideh; Matile, Stefan

    2015-04-13

    This article assembles pertinent insights behind the concept of planarizable push-pull probes. As a response to the planarization of their polarized ground state, a red shift of their excitation maximum is expected to report on either the disorder, the tension, or the potential of biomembranes. The combination of chromophore planarization and polarization contributes to various, usually more complex processes in nature. Examples include the color change of crabs or lobsters during cooking or the chemistry of vision, particularly color vision. The summary of lessons from nature is followed by an overview of mechanosensitive organic materials. Although often twisted and sometimes also polarized, their change of color under pressure usually originates from changes in their crystal packing. Intriguing exceptions include the planarization of several elegantly twisted phenylethynyl oligomers and polymers. Also mechanosensitive probes in plastics usually respond to stretching by disassembly. True ground-state planarization in response to molecular recognition is best exemplified with the binding of thoughtfully twisted cationic polythiophenes to single- and double-stranded oligonucleotides. Molecular rotors, en vogue as viscosity sensors in cells, operate by deplanarization of the first excited state. Pertinent recent examples are described, focusing on λ-ratiometry and intracellular targeting. Complementary to planarization of the ground state with twisted push-pull probes, molecular rotors report on environmental changes with quenching or shifts in emission rather than absorption. The labeling of mechanosensitive channels is discussed as a bioengineering approach to bypass the challenge to create molecular mechanosensitivity and use biological systems instead to sense membrane tension. With planarizable push-pull probes, this challenge is met not with twistome screening, but with "fluorescent flippers," a new concept to insert large and bright monomers into oligomeric

  10. Detection of disseminated peritoneal tumors by fluorescein diacrylate in mice

    NASA Astrophysics Data System (ADS)

    Harada, Yoshinori; Furuta, Hirokazu; Murayama, Yasutoshi; Dai, Ping; Fujikawa, Yuta; Urano, Yasuteru; Nagano, Tetsuo; Morishita, Koki; Hasegawa, Akira; Takamatsu, Tetsuro

    2009-02-01

    Tumor invasion to the peritoneum is a poor prognostic factor in cancer patients. Accurate diagnosis of disseminated peritoneal tumors is essential to accurate cancer staging. To date, peritoneal washing cytology during laparotomy has been used for diagnosis of peritoneal dissemination of gastrointestinal cancer, but its sensitivity has not been satisfactory. Thus, a more direct approach is indispensable to detect peritoneal dissemination in vivo. Fluorescein diacrylate (FDAcr) is an esterase-sensitive fluorescent probe derived from fluorescein. In cancer cells, fluorescent fluorescein generated by exogenous application of FDAcr selectively deposits owing to its stronger hydrolytic enzyme activity and its lower leakage rate. We examined whether FDAcr can specifically detect disseminated peritoneal tumors in athymic nude mouse models. Intraperitoneally administered FDAcr revealed disseminated peritoneal microscopic tumors not readily recognized on white-light imaging. These results suggest that FDAcr is a useful probe for detecting disseminated peritoneal tumors.

  11. EDITORIAL: Probing the nanoworld Probing the nanoworld

    NASA Astrophysics Data System (ADS)

    Miles, Mervyn

    2009-10-01

    In nanotechnology, it is the unique properties arising from nanometre-scale structures that lead not only to their technological importance but also to a better understanding of the underlying science. Over the last twenty years, material properties at the nanoscale have been dominated by the properties of carbon in the form of the C60 molecule, single- and multi-wall carbon nanotubes, nanodiamonds, and recently graphene. During this period, research published in the journal Nanotechnology has revealed the amazing mechanical properties of such materials as well as their remarkable electronic properties with the promise of new devices. Furthermore, nanoparticles, nanotubes, nanorods, and nanowires from metals and dielectrics have been characterized for their electronic, mechanical, optical, chemical and catalytic properties. Scanning probe microscopy (SPM) has become the main characterization technique and atomic force microscopy (AFM) the most frequently used SPM. Over the past twenty years, SPM techniques that were previously experimental in nature have become routine. At the same time, investigations using AFM continue to yield impressive results that demonstrate the great potential of this powerful imaging tool, particularly in close to physiological conditions. In this special issue a collaboration of researchers in Europe report the use of AFM to provide high-resolution topographical images of individual carbon nanotubes immobilized on various biological membranes, including a nuclear membrane for the first time (Lamprecht C et al 2009 Nanotechnology 20 434001). Other SPM developments such as high-speed AFM appear to be making a transition from specialist laboratories to the mainstream, and perhaps the same may be said for non-contact AFM. Looking to the future, characterisation techniques involving SPM and spectroscopy, such as tip-enhanced Raman spectroscopy, could emerge as everyday methods. In all these advanced techniques, routinely available probes will

  12. Enabling interstellar probe

    NASA Astrophysics Data System (ADS)

    McNutt, Ralph L.; Wimmer-Schweingruber, Robert F.; International Interstellar Probe Team

    2011-04-01

    The scientific community has advocated a scientific probe to the interstellar medium for over 30 years. While the Voyager spacecraft have passed through the termination shock of the solar wind, they have limited lifetimes as their radioisotope power supplies decay. It remains unclear whether they can reach the heliopause, the boundary between shocked solar wind and interstellar plasmas, and, in any case, they will not reach the undisturbed interstellar medium. As with most exploratory space missions, their ongoing observations continue to raise even more questions about the nature of the interaction of our heliosphere and the interstellar medium. Scientific questions including: What is the nature of the nearby interstellar medium? How do the Sun and galaxy affect the dynamics of the heliosphere? What is the structure of the heliosphere? How did matter in the solar system and interstellar medium originate and evolve? can only be answered by an "interstellar precursor" probe. Such a mission is required to make in situ measurements in the interaction region and interstellar medium itself at distances far from the Sun, but in a finite mission lifetime. By launching a probe toward the incoming "interstellar wind," whose direction is known, the distance to be traveled can be minimized but is still large. The current consensus is that a scientifically compelling mission must function to at least a distance of 200 astronomical units (AU) from the Sun and return a reasonable stream of data during the voyage. The central problem is that of providing a means of propulsion to accelerate a probe from the Solar System. Even with a low-mass payload and spacecraft, achieving the high speeds needed, even with gravity assists, have remained problematic. Voyager 1, the fastest object ever to leave the system is now traveling ˜3.6 AU/yr, and a credible probe must reach at least 2-3 times this speed. The use of an Ares V is an approach for enabling a fast interstellar precursor

  13. Molecular genetic studies of sporadic pituitary tumors

    SciTech Connect

    Boggild, M.D.; Jenkinson, S.; McTernan, P.; Perrett, C.W.; Clayton, R.N.; Thakker, R.V.; Pistorello, M.; Boscaro, M.; Scanarini, M.

    1994-02-01

    Tumor formation may result from the activation of dominant oncogenes or by inactivation of recessive, tumor suppressor genes. The role of such mutations in the development of pituitary tumors has been studied. Tumors from 88 patients, representing the 4 major classes of adenoma, were investigated. In DNA extracted from matched leukocyte and tumor samples, allelic deletions were sought with 15 probes identifying restriction, fragment length polymorphisms on chromosomes 1, 5, 10, 11, 13, 17, 20, and 22. Evidence of amplification or rearrangement of 10 recognized cellular oncogenes (N-ras, mycL1, mycN, myc, H-ras, bcl1, H-stf1, sea, kraS2, and fos) was sought in tumor DNA. Activating dominant mutations of G{sub s{alpha}} were detected using the polymerase chain reaction to amplify exons 7-10 and hybridizing the product to normal and mutant allele-specific oligonucleotides. Allelic deletions on chromosome 11 were identified in 16 tumors (18%) representing all 4 major subtypes. Deletions on other autosomes were observed in less than 6% of tumors. Three adenomas had deletions on multiple autosomes, 2 of these were aggressive and recurrent. Mutations of G{sub s{alpha}} were confirmed to be specific to somatotrophinomas, being identified in 36% of such tumors in this series. No evidence of amplification or rearrangement of other recognized cellular oncogenes was found. Inactivation of a recessive oncogene on chromosome 11 is an important and possibly early event in the development of the four major types of pituitary adenoma, whereas activating mutations of G{sub s{alpha}} are confirmed to be specific to somatotropinomas. Two aggressive tumors were found to have multiple autosomal losses, suggesting a multistep progression in the development of tumors of this phenotype. 30 refs., 3 figs., 1 tab.

  14. 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.

  15. 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.

  16. Tumor microenvironment–associated modifications of alternative splicing

    PubMed Central

    Brosseau, Jean-Philippe; Lucier, Jean-François; Nwilati, Hanad; Thibault, Philippe; Garneau, Daniel; Gendron, Daniel; Durand, Mathieu; Couture, Sonia; Lapointe, Elvy; Prinos, Panagiotis; Klinck, Roscoe; Perreault, Jean-Pierre; Chabot, Benoit; Abou-Elela, Sherif

    2014-01-01

    Pre-mRNA alternative splicing is modified in cancer, but the origin and specificity of these changes remain unclear. Here, we probed ovarian tumors to identify cancer-associated splicing isoforms and define the mechanism by which splicing is modified in cancer cells. Using high-throughput quantitative PCR, we monitored the expression of splice variants in laser-dissected tissues from ovarian tumors. Surprisingly, changes in alternative splicing were not limited to the tumor tissues but were also found in the tumor microenvironment. Changes in the tumor-associated splicing events were found to be regulated by splicing factors that are differentially expressed in cancer tissues. Overall, ∼20% of the alternative splicing events affected by the down-regulation of the splicing factors QKI and RBFOX2 were altered in the microenvironment of ovarian tumors. Together, our results indicate that the tumor microenvironment undergoes specific changes in alternative splicing orchestrated by a limited number of splicing factors. PMID:24335142

  17. Tumor microenvironment-associated modifications of alternative splicing.

    PubMed

    Brosseau, Jean-Philippe; Lucier, Jean-François; Nwilati, Hanad; Thibault, Philippe; Garneau, Daniel; Gendron, Daniel; Durand, Mathieu; Couture, Sonia; Lapointe, Elvy; Prinos, Panagiotis; Klinck, Roscoe; Perreault, Jean-Pierre; Chabot, Benoit; Abou-Elela, Sherif

    2014-02-01

    Pre-mRNA alternative splicing is modified in cancer, but the origin and specificity of these changes remain unclear. Here, we probed ovarian tumors to identify cancer-associated splicing isoforms and define the mechanism by which splicing is modified in cancer cells. Using high-throughput quantitative PCR, we monitored the expression of splice variants in laser-dissected tissues from ovarian tumors. Surprisingly, changes in alternative splicing were not limited to the tumor tissues but were also found in the tumor microenvironment. Changes in the tumor-associated splicing events were found to be regulated by splicing factors that are differentially expressed in cancer tissues. Overall, ∼20% of the alternative splicing events affected by the down-regulation of the splicing factors QKI and RBFOX2 were altered in the microenvironment of ovarian tumors. Together, our results indicate that the tumor microenvironment undergoes specific changes in alternative splicing orchestrated by a limited number of splicing factors.

  18. Experiments with probe masses

    PubMed Central

    Braginsky, V. B.

    2007-01-01

    It is reasonable to regard the experiments performed by C. Coulomb and H. Cavendish in the end of the 18th century as the beginning of laboratory experimental physics. These outstanding scientists have measured forces (accelerations) produced by electric charges and by gravitational “charges” on probe masses that were attached to torque balance. Among the variety of different research programs and projects existing today, experiments with probe masses are still playing an important role. In this short review, the achieved and planned sensitivities of very challenging LIGO (Laser Interferometer Gravitational wave Observatory) and LISA (Laser Interferometer Space Antennae) projects are described, and a list of nonsolved problems is discussed as well. The role of quantum fluctuations in high precision measurements is also outlined. Apart from these main topics, the limitations of sensitivity caused by cosmic rays and the prospects of clock frequency stability are presented. PMID:17296944

  19. Temperature averaging thermal probe

    NASA Technical Reports Server (NTRS)

    Kalil, L. F.; Reinhardt, V. (Inventor)

    1985-01-01

    A thermal probe to average temperature fluctuations over a prolonged period was formed with a temperature sensor embedded inside a solid object of a thermally conducting material. The solid object is held in a position equidistantly spaced apart from the interior surfaces of a closed housing by a mount made of a thermally insulating material. The housing is sealed to trap a vacuum or mass of air inside and thereby prevent transfer of heat directly between the environment outside of the housing and the solid object. Electrical leads couple the temperature sensor with a connector on the outside of the housing. Other solid objects of different sizes and materials may be substituted for the cylindrically-shaped object to vary the time constant of the probe.

  20. 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.

  1. Experiments with probe masses.

    PubMed

    Braginsky, V B

    2007-03-06

    It is reasonable to regard the experiments performed by C. Coulomb and H. Cavendish in the end of the 18th century as the beginning of laboratory experimental physics. These outstanding scientists have measured forces (accelerations) produced by electric charges and by gravitational "charges" on probe masses that were attached to torque balance. Among the variety of different research programs and projects existing today, experiments with probe masses are still playing an important role. In this short review, the achieved and planned sensitivities of very challenging LIGO (Laser Interferometer Gravitational wave Observatory) and LISA (Laser Interferometer Space Antennae) projects are described, and a list of nonsolved problems is discussed as well. The role of quantum fluctuations in high precision measurements is also outlined. Apart from these main topics, the limitations of sensitivity caused by cosmic rays and the prospects of clock frequency stability are presented.

  2. Gravity Probe B

    NASA Image and Video Library

    2003-07-12

    The Gravity Probe B experiment is lifted from its transporter in the spacecraft processing facility on North Vandenberg Air Force Base. Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  3. Gravity Probe B

    NASA Image and Video Library

    2003-07-12

    The Gravity Probe B experiment is lowered onto an assembly and test stand in the spacecraft processing facility on North Vandenberg Air Force Base. Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  4. Gravity Probe B

    NASA Image and Video Library

    2003-07-13

    In the spacecraft processing facility on North Vandenberg Air Force Base, workers prepare to remove the soft shipping cover from the Gravity Probe B experiment. Immediate processing includes setting up mechanical and electrical ground support equipment, making necessary connections and conditioning the spacecraft battery. The Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  5. Gravity Probe B

    NASA Image and Video Library

    2003-07-18

    In the spacecraft processing facility on North Vandenberg Air Force Base, workers conduct battery charge/discharge cycles as part of the battery conditioning process on Gravity Probe B. The Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  6. Gravity Probe B

    NASA Image and Video Library

    2003-07-12

    The Gravity Probe B experiment enters the spacecraft processing facility on North Vandenberg Air Force Base. Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  7. Gravity Probe B

    NASA Image and Video Library

    2003-07-12

    A transporter carrying the Gravity Probe B experiment backs into the spacecraft processing facility on North Vandenberg Air Force Base. Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  8. Gravity Probe B

    NASA Image and Video Library

    2003-07-12

    Enclosed in a canister, the Gravity Probe B (GP-B) spacecraft arrives on Vandenberg Air Force Base, headed for the spacecraft processing facility. Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  9. Gravity Probe B

    NASA Image and Video Library

    2003-07-11

    Workers in the spacecraft processing facility on North Vandenberg Air Force Base get ready to begin processing the Gravity Probe B experiment, including setting up mechanical and electrical ground support equipment, making necessary connections and conditioning the spacecraft battery. The Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  10. Gravity Probe B

    NASA Image and Video Library

    2003-07-12

    The Gravity Probe B experiment rests on an assembly and test stand in the spacecraft processing facility on North Vandenberg Air Force Base. Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  11. Gravity Probe B

    NASA Image and Video Library

    2003-07-12

    At Vandenberg AFB, the canister enclosing the Gravity Probe B (GP-B) spacecraft is removed from the transporter. Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  12. Gravity Probe B

    NASA Image and Video Library

    2003-07-11

    Workers in the spacecraft processing facility on North Vandenberg Air Force Base get ready to begin processing the Gravity Probe B experiment. Mechanical and electrical ground support equipment will be set up and necessary connections made with the spacecraft. Spacecraft battery conditioning will also begin. The Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  13. Gravity Probe B

    NASA Image and Video Library

    2003-07-18

    In the spacecraft processing facility on North Vandenberg Air Force Base, battery charge/discharge cycles are underway as part of the battery conditioning process on Gravity Probe B. The Gravity Probe B will launch a payload of four gyroscopes into low-Earth polar orbit to test two extraordinary predictions of Albert Einstein’s general theory of relativity: the geodetic effect (how space and time are warped by the presence of the Earth) and frame dragging (how Earth’s rotation drags space and time around with it). Once in orbit, for 18 months each gyroscope’s spin axis will be monitored as it travels through local spacetime, observing and measuring these effects. The experiment was developed by Stanford University, Lockheed Martin and NASA’s Marshall Space Flight Center.

  14. Subsurface Ice Probe

    NASA Technical Reports Server (NTRS)

    Hecht, Michael; Carsey, Frank

    2005-01-01

    The subsurface ice probe (SIPR) is a proposed apparatus that would bore into ice to depths as great as hundreds of meters by melting the ice and pumping the samples of meltwater to the surface. Originally intended for use in exploration of subsurface ice on Mars and other remote planets, the SIPR could also be used on Earth as an alternative to coring, drilling, and melting apparatuses heretofore used to sample Arctic and Antarctic ice sheets. The SIPR would include an assembly of instrumentation and electronic control equipment at the surface, connected via a tether to a compact assembly of boring, sampling, and sensor equipment in the borehole (see figure). Placing as much equipment as possible at the surface would help to attain primary objectives of minimizing power consumption, sampling with high depth resolution, and unobstructed imaging of the borehole wall. To the degree to which these requirements would be satisfied, the SIPR would offer advantages over the aforementioned ice-probing systems.

  15. Temperature averaging thermal probe

    NASA Astrophysics Data System (ADS)

    Kalil, L. F.; Reinhardt, V.

    1985-12-01

    A thermal probe to average temperature fluctuations over a prolonged period was formed with a temperature sensor embedded inside a solid object of a thermally conducting material. The solid object is held in a position equidistantly spaced apart from the interior surfaces of a closed housing by a mount made of a thermally insulating material. The housing is sealed to trap a vacuum or mass of air inside and thereby prevent transfer of heat directly between the environment outside of the housing and the solid object. Electrical leads couple the temperature sensor with a connector on the outside of the housing. Other solid objects of different sizes and materials may be substituted for the cylindrically-shaped object to vary the time constant of the probe.

  16. Spectral and lifetime domain measurements of rat brain tumors.

    PubMed

    Haidar, D Abi; Leh, B; Zanello, M; Siebert, R

    2015-04-01

    During glioblastoma surgery, delineation of the brain tumor margins is difficult because the infiltrated and normal tissues have the same visual appearance. We use a fiber-optical fluorescence probe for spectroscopic and time domain measurements to assist surgeon in differentiating the healthy and the infiltrated tissues. First study was performed on rats that were previously injected with tumorous cells. Measurements of endogenous tissue fluorescence were performed on fresh and fixed rat tumor brain slices. Spectral characteristics, fluorescence redox ratios and fluorescence lifetime measurements were analyzed. The study aimed at defining an optical index that can act as an indicator for discriminating healthy from tumorous tissue.

  17. Progesterone-Targeted Magnetic Resonance Imaging Probes

    PubMed Central

    2015-01-01

    Determination of progesterone receptor (PR) status in hormone-dependent diseases is essential in ascertaining disease prognosis and monitoring treatment response. The development of a noninvasive means of monitoring these processes would have significant impact on early detection, cost, repeated measurements, and personalized treatment options. Magnetic resonance imaging (MRI) is widely recognized as a technique that can produce longitudinal studies, and PR-targeted MR probes may address a clinical problem by providing contrast enhancement that reports on PR status without biopsy. Commercially available MR contrast agents are typically delivered via intravenous injection, whereas steroids are administered subcutaneously. Whether the route of delivery is important for tissue accumulation of steroid-modified MRI contrast agents to PR-rich tissues is not known. To address this question, modification of the chemistry linking progesterone with the gadolinium chelate led to MR probes with increased water solubility and lower cellular toxicity and enabled administration through the blood. This attribute came at a cost through lower affinity for PR and decreased ability to cross the cell membrane, and ultimately it did not improve delivery of the PR-targeted MR probe to PR-rich tissues or tumors in vivo. Overall, these studies are important, as they demonstrate that targeted contrast agents require optimization of delivery and receptor binding of the steroid and the gadolinium chelate for optimal translation in vivo. PMID:25019183

  18. Molecular Optical Imaging with Radioactive Probes

    PubMed Central

    Liu, Hongguang; Ren, Gang; Miao, Zheng; Zhang, Xiaofen; Tang, Xiaodong; Han, Peizhen; Gambhir, Sanjiv S.; Cheng, Zhen

    2010-01-01

    Background Optical imaging (OI) techniques such as bioluminescence and fluorescence imaging have been widely used to track diseases in a non-invasive manner within living subjects. These techniques generally require bioluminescent and fluorescent probes. Here we demonstrate the feasibility of using radioactive probes for in vivo molecular OI. Methodology/Principal Findings By taking the advantages of low energy window of light (1.2–3.1 eV, 400–1000 nm) resulting from radiation, radionuclides that emit charged particles such as β+ and β− can be successfully imaged with an OI instrument. In vivo optical images can be obtained for several radioactive probes including 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), Na18F, Na131I, 90YCl3 and a 90Y labeled peptide that specifically target tumors. Conclusions/Significance These studies demonstrate generalizability of radioactive OI technique. It provides a new molecular imaging strategy and will likely have significant impact on both small animal and clinical imaging. PMID:20208993

  19. 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)

  20. Droplet monitoring probe

    NASA Technical Reports Server (NTRS)

    Baughman, J. R.; Thys, P. C.

    1973-01-01

    A droplet monitoring system is disclosed for analysis of mixed-phase fluid flow in development of gas turbines. The system uses a probe comprising two electrical wires spaced a known distance apart and connected at one end to means for establishing a dc potential between the wires. A drop in the fluid stream momentarily contacting both wires simultaneously causes and electrical signal which is amplified, detected and counted.

  1. 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.

  2. Probing pathways periodically.

    PubMed

    Elston, Timothy C

    2008-10-21

    Signal transduction pathways are used by cells to process and transmit information about their external surroundings. These systems are dynamic, interconnected molecular networks. Therefore, full characterization of their behavior requires a systems-level analysis. Investigations with temporally oscillating input signals probed the dynamic properties of the high-osmolarity glycerol (HOG) pathway of the budding yeast Saccharomyces cerevisiae. These studies shed light on how the network functions as a whole to respond to changing environmental conditions.

  3. 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

  4. 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.

  5. Interstitial Inorganic Phosphate as a Tumor Microenvironment Marker for Tumor Progression

    PubMed Central

    Bobko, Andrey A.; Eubank, Timothy D.; Driesschaert, Benoit; Dhimitruka, Ilirian; Evans, Jason; Mohammad, Rahman; Tchekneva, Elena E.; Dikov, Mikhail M.; Khramtsov, Valery V.

    2017-01-01

    Noninvasive in vivo assessment of chemical tumor microenvironment (TME) parameters such as oxygen (pO2), extracellular acidosis (pHe), and concentration of interstitial inorganic phosphate (Pi) may provide unique insights into biological processes in solid tumors. In this work, we employ a recently developed multifunctional trityl paramagnetic probe and electron paramagnetic resonance (EPR) technique for in vivo concurrent assessment of these TME parameters in various mouse models of cancer. While the data support the existence of hypoxic and acidic regions in TME, the most dramatic differences, about 2-fold higher concentrations in tumors vs. normal tissues, were observed for interstitial Pi - the only parameter that also allowed for discrimination between non-metastatic and highly metastatic tumors. Correlation analysis between [Pi], pO2, pHe and tumor volumes reveal an association of high [Pi] with changes in tumor metabolism and supports different mechanisms of protons and Pi accumulation in TME. Our data identifies interstitial inorganic phosphate as a new TME marker for tumor progression. Pi association with tumor metabolism, buffer-mediated proton transport, and a requirement of high phosphorus content for the rapid growth in the “growth rate hypothesis” may underline its potential role in tumorigenesis and tumor progression. PMID:28117423

  6. Probing dimensionality using a simplified 4-probe method

    NASA Astrophysics Data System (ADS)

    Kjeldby, Snorre B.; Evenstad, Otto M.; Cooil, Simon P.; Wells, Justin W.

    2017-10-01

    4-probe electrical measurements have been in existence for many decades. One of the most useful aspects of the 4-probe method is that it is not only possible to find the resistivity of a sample (independently of the contact resistances), but that it is also possible to probe the dimensionality of the sample. In theory, this is straightforward to achieve by measuring the 4-probe resistance as a function of probe separation. In practice, it is challenging to move all four probes with sufficient precision over the necessary range. Here, we present an alternative approach. We demonstrate that the dimensionality of the conductive path within a sample can be directly probed using a modified 4-probe method in which an unconventional geometry is exploited; three of the probes are rigidly fixed, and the position of only one probe is changed. This allows 2D and 3D (and other) contributions the to resistivity to be readily disentangled. The required experimental instrumentation can be vastly simplified relative to traditional variable spacing 4-probe instruments.

  7. Brain Tumors (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Brain Tumors KidsHealth > For Parents > Brain Tumors A A ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  8. DCB - Tumor Metastasis Research

    Cancer.gov

    Tumor metastasis research examines the mechanisms that allow cancer cells to leave the primary tumor and spread to another part of the body. Learn about recent tumor metastasis research studies supported by the Division of Cancer Biology.

  9. 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

  10. Neuroendocrine Tumor: Statistics

    MedlinePlus

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on how many people survive this type of ...

  11. 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. ...

  12. Pediatric Brain Tumor Foundation

    MedlinePlus

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

  13. Brain Tumors (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old 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 ...

  14. 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 ...

  15. 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

  16. An Activatable Near Infrared Fluorescent Probe for In Vivo Imaging of Fibroblast Activation Protein-alpha

    PubMed Central

    Li, Jinbo; Chen, Kai; Liu, Hongguang; Cheng, Kai; Yang, Meng; Zhang, Jiping; Cheng, Jonathan D.; Zhang, Yan; Cheng, Zhen

    2012-01-01

    Fibroblast activation protein-alpha (FAPα) is a cell surface glycoprotein which is selectively expressed by tumor-associated fibroblasts in malignant tumors but rarely on normal tissues. FAPα has also been reported to promote tumor growth and invasion and therefore has been of increasing interest as a promising target for designing tumor-targeted drugs and imaging agents. Although medicinal study on FAPα inhibitors has led to the discovery of many FAPα-targeting inhibitors including a drug candidate in a phase II clinical trial, the development of imaging probes to monitor the expression and activity of FAPα in vivo has largely lagged behind. Herein we report an activatable near infrared (NIR) fluorescent probe (ANPFAP) for in vivo optical imaging of FAPα. The ANPFAP consists of a NIR dye (Cy5.5) and a quencher dye (QSY21) which are linked together by a short peptide sequence (KGPGPNQC) specific for FAPα cleavage. Because of the efficient fluorescence resonance energy transfer (FRET) between Cy5.5 and QSY21 in ANPFAP, high contrast on the NIR fluorescence signal can be achieved after the cleavage of the peptide sequence by FAPα both in vitro and in vivo. In vitro assay on ANPFAP indicated the specificity of the probe to FAPα. The in vivo optical imaging using ANPFAP showed fast tumor uptake as well as high tumor to background contrast on U87MG tumor models with FAPα expression, while much lower signal and tumor contrast were observed in the C6 tumor without FAPα expression, demonstrating the in vivo targeting specificity of the ANPFAP. Ex vivo imaging also demonstrated ANPFAP had high tumor uptake at 4 h post injection. Collectively, these results indicated that ANPFAP could serve as a useful NIR optical probe for early detection of FAPα expressing tumors. PMID:22812530

  17. Tumor gangliosides accelerate murine tumor angiogenesis.

    PubMed

    Liu, Yihui; Wondimu, Assefa; Yan, Su; Bobb, Daniel; Ladisch, Stephan

    2014-07-01

    Tumor cells shed gangliosides and populate their microenvironment with these biologically active membrane glycosphingolipids. In vitro, ganglioside enrichment amplifies receptor tyrosine kinase signaling and activation of vascular endothelial cells. However, a long-standing question is whether in the actual microenvironment of a neoplasm, in vivo, tumor cell ganglioside shedding stimulates angiogenesis. Here we tested the hypothesis that tumor gangliosides have a critical proangiogenic role in vivo using novel murine tumor cells, GM3synthase/GM2synthase double knockout (DKO) cells, genetically completely incapable of ganglioside synthesis and impaired in tumor growth versus wild-type (WT) ganglioside-rich cells. We studied angiogenesis during tumor formation by these ganglioside-depleted cells, quantifying vessel formation, angiogenic factor production/release, and consequences of reconstitution with purified WT gangliosides. DKO cells formed virtually avascular tumors, much smaller than ganglioside-rich WT tumors and displaying a striking paucity of blood vessels, despite levels of VEGF and other angiogenic factors that were similar to those of WT cells. Transient enrichment of the ganglioside milieu of the DKO cell inoculum by adding purified WT gangliosides partially restored angiogenesis and tumor growth. We conclude that tumor gangliosides trigger robust angiogenesis important for tumor growth. Our findings suggest strategies to eliminate their synthesis and shedding by tumor cells should be pursued.

  18. Tumor gangliosides accelerate murine tumor angiogenesis

    PubMed Central

    Liu, Yihui; Wondimu, Assefa; Yan, Su; Bob, Daniel; Ladisch, Stephan

    2013-01-01

    Tumor cells shed gangliosides and populate their microenvironment with these biologically active membrane glycosphingolipids. In vitro, ganglioside enrichment amplifies receptor tyrosine kinase signaling and activation of vascular endothelial cells. However, a long-standing question is whether in the actual microenvironment of a neoplasm, in vivo, tumor cell ganglioside shedding stimulates angiogenesis. Here we tested the hypothesis that tumor gangliosides have a critical proangiogenic role in vivo using novel murine tumor cells (DKO) genetically completely incapable of ganglioside synthesis and impaired in tumor growth vs. wild-type (WT) ganglioside-rich cells. We studied angiogenesis during tumor formation by these ganglioside-depleted cells, quantifying vessel formation, angiogenic factor production/release, and consequences of reconstitution with purified WT gangliosides. DKO cells formed virtually avascular tumors, much smaller than ganglioside-rich WT tumors and displaying a striking paucity of blood vessels, despite levels of VEGF and other angiogenic factors that were similar to those of WT cells. Transient enrichment of the ganglioside milieu of the DKO cell inoculum by adding purified WT gangliosides partially restored angiogenesis and tumor growth. We conclude that tumor gangliosides trigger robust angiogenesis important for tumor growth. Our findings suggest strategies to eliminate their synthesis and shedding by tumor cells should be pursued. PMID:24165965

  19. 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

  20. A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer

    PubMed Central

    Whitley, Melodi Javid; Cardona, Diana M.; Lazarides, Alexander L.; Spasojevic, Ivan; Ferrer, Jorge M.; Cahill, Joan; Lee, Chang-Lung; Snuderl, Matija; Blazer, Dan G.; Hwang, E. Shelley; Greenup, Rachel A.; Mosca, Paul J.; Mito, Jeffrey K.; Cuneo, Kyle C.; Larrier, Nicole A.; O’Reilly, Erin K.; Riedel, Richard F.; Eward, William C.; Strasfeld, David B.; Fukumura, Dai; Jain, Rakesh K.; Lee, W. David; Griffith, Linda G.; Bawendi, Moungi G.; Kirsch, David G.; Brigman, Brian E.

    2016-01-01

    Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial. In mice, intravenous injection of LUM015 labeled tumor cells, and residual fluorescence within the tumor bed predicted local recurrence. In 15 patients with STS or breast cancer, intravenous injection of LUM015 before surgery was well tolerated. Imaging of resected human tissues showed that fluorescence from tumor was significantly higher than fluorescence from normal tissues. LUM015 biodistribution, pharmacokinetic profiles, and metabolism were similar in mouse and human subjects. Tissue concentrations of LUM015 and its metabolites, including fluorescently labeled lysine, demonstrated that LUM015 is selectively distributed to tumors where it is activated by proteases. Experiments in mice with a constitutively active PEGylated fluorescent imaging probe support a model where tumor-selective probe distribution is a determinant of increased fluorescence in cancer. These co-clinical studies suggest that the tumor specificity of protease-activated imaging probes, such as LUM015, is dependent on both biodistribution and enzyme activity. Our first-in-human data support future clinical trials of LUM015 and other protease-sensitive probes. PMID:26738797

  1. A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer.

    PubMed

    Whitley, Melodi Javid; Cardona, Diana M; Lazarides, Alexander L; Spasojevic, Ivan; Ferrer, Jorge M; Cahill, Joan; Lee, Chang-Lung; Snuderl, Matija; Blazer, Dan G; Hwang, E Shelley; Greenup, Rachel A; Mosca, Paul J; Mito, Jeffrey K; Cuneo, Kyle C; Larrier, Nicole A; O'Reilly, Erin K; Riedel, Richard F; Eward, William C; Strasfeld, David B; Fukumura, Dai; Jain, Rakesh K; Lee, W David; Griffith, Linda G; Bawendi, Moungi G; Kirsch, David G; Brigman, Brian E

    2016-01-06

    Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial. In mice, intravenous injection of LUM015 labeled tumor cells, and residual fluorescence within the tumor bed predicted local recurrence. In 15 patients with STS or breast cancer, intravenous injection of LUM015 before surgery was well tolerated. Imaging of resected human tissues showed that fluorescence from tumor was significantly higher than fluorescence from normal tissues. LUM015 biodistribution, pharmacokinetic profiles, and metabolism were similar in mouse and human subjects. Tissue concentrations of LUM015 and its metabolites, including fluorescently labeled lysine, demonstrated that LUM015 is selectively distributed to tumors where it is activated by proteases. Experiments in mice with a constitutively active PEGylated fluorescent imaging probe support a model where tumor-selective probe distribution is a determinant of increased fluorescence in cancer. These co-clinical studies suggest that the tumor specificity of protease-activated imaging probes, such as LUM015, is dependent on both biodistribution and enzyme activity. Our first-in-human data support future clinical trials of LUM015 and other protease-sensitive probes.

  2. Comparison of NaI(T1), CdTe, and HgI2 surgical probes: effect of scatter compensation on probe performance.

    PubMed

    Kwo, D P; Barber, H B; Barrett, H H; Hickernell, T S; Woolfenden, J M

    1991-01-01

    Spatial variation in the background source distribution makes tumor detection difficult for single-detector probes. Using a single energy window that brackets the photopeak helps discriminate against background events dominated by Compton scattering. Another approach is to use the information provided by an additional window in the Compton region. The performances of NaI(T1), CdTe, and HgI2 surgical probes have been compared under realistic simulations of a tumor-staging procedure using optimal single-sided energy windows and a two-window scatter-subtraction technique. Results showed that despite the differences in energy resolution of the detectors, the performances of the probes in a variable background were similar when optimal single energy windows were used. When the background variations were large, using information provided by a second window improved probe performance.

  3. Development of Mackintosh Probe Extractor

    NASA Astrophysics Data System (ADS)

    Rahman, Noor Khazanah A.; Kaamin, Masiri; Suwandi, Amir Khan; Sahat, Suhaila; Jahaya Kesot, Mohd

    2016-11-01

    Dynamic probing is a continuous soil investigation technique, which is one of the simplest soil penetration test. It basically consist of repeatedly driving a metal tipped probe into the ground using a drop weight of fixed mass and travel. Testing was carried out continuously from ground level to the final penetration depth. Once the soil investigation work done, it is difficult to pull out the probe rod from the ground, due to strong soil structure grip against probe cone and prevent the probe rod out from the ground. Thus, in this case, a tool named Extracting Probe was created to assist in the process of retracting the probe rod from the ground. In addition, Extracting Probe also can reduce the time to extract the probe rod from the ground compare with the conventional method. At the same time, it also can reduce manpower cost because only one worker involve to handle this tool compare with conventional method used two or more workers. From experiment that have been done we found that the time difference between conventional tools and extracting probe is significant, average time difference is 155 minutes. In addition the extracting probe can reduce manpower usage, and also labour cost for operating the tool. With all these advantages makes this tool has the potential to be marketed.

  4. PROcess Based Diagnostics PROBE

    NASA Technical Reports Server (NTRS)

    Clune, T.; Schmidt, G.; Kuo, K.; Bauer, M.; Oloso, H.

    2013-01-01

    Many of the aspects of the climate system that are of the greatest interest (e.g., the sensitivity of the system to external forcings) are emergent properties that arise via the complex interplay between disparate processes. This is also true for climate models most diagnostics are not a function of an isolated portion of source code, but rather are affected by multiple components and procedures. Thus any model-observation mismatch is hard to attribute to any specific piece of code or imperfection in a specific model assumption. An alternative approach is to identify diagnostics that are more closely tied to specific processes -- implying that if a mismatch is found, it should be much easier to identify and address specific algorithmic choices that will improve the simulation. However, this approach requires looking at model output and observational data in a more sophisticated way than the more traditional production of monthly or annual mean quantities. The data must instead be filtered in time and space for examples of the specific process being targeted.We are developing a data analysis environment called PROcess-Based Explorer (PROBE) that seeks to enable efficient and systematic computation of process-based diagnostics on very large sets of data. In this environment, investigators can define arbitrarily complex filters and then seamlessly perform computations in parallel on the filtered output from their model. The same analysis can be performed on additional related data sets (e.g., reanalyses) thereby enabling routine comparisons between model and observational data. PROBE also incorporates workflow technology to automatically update computed diagnostics for subsequent executions of a model. In this presentation, we will discuss the design and current status of PROBE as well as share results from some preliminary use cases.

  5. 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.

  6. Controlled Scanning Probe Lithography

    NASA Astrophysics Data System (ADS)

    Ruskell, Todd G.; Sarid, Dror; Workman, Richard K.; Pyle, Jason L.

    1997-03-01

    A method for real-time monitoring of the quality and quantity of silicon oxide grown on silicon using conducting-tip scanning probe lithography has been developed. The sub-picoampere tip-sample currents measured during lithography in ambient conditions are shown to be proportional to the amount of silicon oxide being grown. In addition, we have demonstrated the ability to control the composition of the grown material by altering the lithographic environment. Silicon nitride growth is shown to result from lithography on silicon samples in an environment of annhydrous ammonia.

  7. 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.

  8. Design optimization and performances of an intraoperative positron imaging probe for radioguided cancer surgery

    NASA Astrophysics Data System (ADS)

    Spadola, S.; Verdier, M.-A.; Pinot, L.; Esnault, C.; Dinu, N.; Charon, Y.; Duval, M.-A.; Ménard, L.

    2016-12-01

    Extent and accuracy of surgical resection is a crucial step in operable tumor therapy. Emergence of promising specific tumor-seeking agents labeled with positron emitters is giving rise to a renewed interest for radioguided surgery using beta probes. Beta detection, due to the particle short range, allows a more sensitive and accurate tumor localization compared to gamma radiotracers. In that context, we are currently developing an intraoperative positron imaging probe using SiPM photosensors to perform tumor localization and post-operative control of the surgical cavity. Because compactness is a key feature when trying to detect positron emitters with high sensitivity in small surgical cavities, we chose to study the simplest detector design based on the use of a very thin organic scintillator coupled to the photosensor. Different designs of the positron imaging probe, including scintillator material and thickness, light spreading window and optical reflector, were investigated with Monte-Carlo simulations and measurements. Their impact on the probe performances were optimized in terms of positron sensitivity, gamma rays background noise contamination, spatial resolution and bias and uniformity. The ability of the probes to detect small radiolabeled tumors was also investigated by simulating different phantom uptake configurations.

  9. Effects of probe geometry on transscleral diffuse optical spectroscopy

    PubMed Central

    Svenmarker, Pontus; Xu, Can T.; Andersson-Engels, Stefan; Krohn, Jørgen

    2011-01-01

    The purpose of this study was to investigate how the geometry of a fiber optic probe affects the transmission and reflection of light through the scleral eye wall. Two geometrical parameters of the fiber probe were investigated: the source-detector distance and the fiber protrusion, i.e. the length of the fiber extending from the flat surface of the fiber probe. For optimization of the fiber optic probe geometry, fluorescence stained choroidal tumor phantoms in ex vivo porcine eyes were measured with both diffuse reflectance- and laser-induced fluorescence spectroscopy. The strength of the fluorescence signal compared to the excitation signal was used as a measure for optimization. Intraocular pressure (IOP) and temperature were monitored to assess the impact of the probe on the eye. For visualizing any possible damage caused by the probe, the scleral surface was imaged with scanning electron microscopy after completion of the spectroscopic measurements. A source-detector distance of 5 mm with zero fiber protrusion was considered optimal in terms of spectroscopic contrast, however, a slight fiber protrusion of 0.5 mm is argued to be advantageous for clinical measurements. The study further indicates that transscleral spectroscopy can be safely performed in human eyes under in vivo conditions, without leading to an unacceptable IOP elevation, a significant rise in tissue temperature, or any visible damage to the scleral surface. PMID:22076267

  10. Magnetomotive molecular probes for targeted contrast enhancement and therapy

    NASA Astrophysics Data System (ADS)

    Boppart, Stephen A.

    2011-03-01

    The diagnostic, interrogational, and therapeutic potential of molecular probes is rapidly being investigated and exploited across virtually every biomedical imaging modality. While many types of probes enhance contrast or delivery therapy by static localization to targeted sites, significant potential exists for utilizing dynamic molecular probes. Recent examples include molecular beacons, photoactivatable probes, or controlled switchable drug-releasing particles, to name a few. In this review, we describe a novel class of dynamic molecular probes that rely on the application and control of localized external magnetic fields. These magnetomotive molecular probes can provide optical image contrast through a modulated scattering signal, can interrogate the biomechanical properties of their viscoelastic microenvironment by tracking their underdamped oscillatory step-response to applied fields, and can potentially delivery therapy through nanometer-to-micrometer mechanical displacement or local hyperthermia. This class of magnetomotive agents includes not only magnetic iron-oxide nanoparticles, but also new magnetomotive microspheres or nanostructures with embedded iron-oxide agents. In vitro three-dimensional cell assays and in vivo targeting studies in animal tumor models have demonstrated the potential for multimodal detection and imaging, using magnetic resonance imaging for whole-body localization, and magnetomotive optical coherence tomography for high-resolution localization and imaging.

  11. 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.

  12. The intraoperative gamma probe: basic principles and choices available.

    PubMed

    Zanzonico, P; Heller, S

    2000-01-01

    By taking advantage of the proximity to radioactive sentinel nodes and occult tumors achievable in an operative setting, intraoperative probes are becoming increasingly important in the surgical management of cancer. This article begins with a discussion of the statistical limitations of radiation detection and measurement and of the key performance parameters (sensitivity, energy resolution, and spatial resolution) that characterize detectors. The basic design and operating principle of radiation detectors used in intraoperative probes, scintillation and semiconductor detectors, are then reviewed. Scintillation detector-based intraoperative probes, generally using a NaI(T1) or a CsI(T1) crystal connected to a photomultiplier tube by a fiberoptic cable, have the advantages of reliability, relatively low cost, and high sensitivity, especially for medium- to high-energy photons. Disadvantages include poor energy resolution and scatter rejection, and bulkiness. Semiconductor (CdZn, CdZnTe, HgI2)-based probes are compact and have excellent energy resolution and scatter rejection, but with complex energy spectra reflecting charge-carrier trapping. Their main disadvantage is lower sensitivity. The performance parameters of various commercially available intraoperative probes are then compared. The article concludes with a discussion of the practical considerations in selecting and using intraoperative probes, including ergonomic and other design features, as well as performance parameters.

  13. Treatment for Gastrointestinal Stromal Tumors (GISTs) Based on Tumor Spread

    MedlinePlus

    ... Stromal Tumor Chemotherapy for Gastrointestinal Stromal Tumor Radiation Therapy for Gastrointestinal Stromal Tumor Treatment Choices for Gastrointestinal Stromal Tumor Based on Tumor ... Cancer Information Cancer Prevention & Detection Cancer Basics ...

  14. Facilitating in vivo tumor localization by principal component analysis based on dynamic fluorescence molecular imaging.

    PubMed

    Gao, Yang; Chen, Maomao; Wu, Junyu; Zhou, Yuan; Cai, Chuangjian; Wang, Daliang; Luo, Jianwen

    2017-09-01

    Fluorescence molecular imaging has been used to target tumors in mice with xenograft tumors. However, tumor imaging is largely distorted by the aggregation of fluorescent probes in the liver. A principal component analysis (PCA)-based strategy was applied on the in vivo dynamic fluorescence imaging results of three mice with xenograft tumors to facilitate tumor imaging, with the help of a tumor-specific fluorescent probe. Tumor-relevant features were extracted from the original images by PCA and represented by the principal component (PC) maps. The second principal component (PC2) map represented the tumor-related features, and the first principal component (PC1) map retained the original pharmacokinetic profiles, especially of the liver. The distribution patterns of the PC2 map of the tumor-bearing mice were in good agreement with the actual tumor location. The tumor-to-liver ratio and contrast-to-noise ratio were significantly higher on the PC2 map than on the original images, thus distinguishing the tumor from its nearby fluorescence noise of liver. The results suggest that the PC2 map could serve as a bioimaging marker to facilitate in vivo tumor localization, and dynamic fluorescence molecular imaging with PCA could be a valuable tool for future studies of in vivo tumor metabolism and progression. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  15. Endocrine Tumor: Overview

    MedlinePlus

    ... are here Home > Types of Cancer > Endocrine Tumor Endocrine Tumor This is Cancer.Net’s Guide to Endocrine Tumor. Use the menu below to choose the ... social workers, and patient advocates. Cancer.Net Guide Endocrine Tumor Introduction Statistics Risk Factors Symptoms and Signs ...

  16. A synopsis of PROBES

    NASA Astrophysics Data System (ADS)

    Goering, J. J.; McRoy, C. P.

    The Processes and Resources of the Bering Sea Shelf (PROBES) project is a 6-year multi-institutional (University of Alaska, Florida State University, University of Washington, Brookhaven National Laboratory, Southwest Fisheries Center, Bigelow Laboratory for Ocean Sciences) interdisciplinary study designed to understand the processes that contribute to the production of enormous numbers of animals (including crabs, fish, birds, mammals) in secondary and higher trophic levels in the vast Bering Sea continental shelf. The research plan is based on the hypothesis that the broad shallow shelf leads to an oceanographic structure of a semi-permanent front-interfront system in which phytoplankton primary production is coupled to a pelagic food web over the outer shelf and to a benthic food web in the middle shelf (see cover, this issue). The project has concentrated on the processes that control the survival of the early life history stages of the Alaska pollock (Theragra chalcogramma Pallas) as an example of mass and energy transfer in the pelagic system. PROBES began in 1976 and is sponsored by the Division of Polar Programs, National Science Foundation.

  17. Epidemiology of Brain Tumors.

    PubMed

    McNeill, Katharine A

    2016-11-01

    Brain tumors are the commonest solid tumor in children, leading to significant cancer-related mortality. Several hereditary syndromes associated with brain tumors are nonfamilial. Ionizing radiation is a well-recognized risk factor for brain tumors. Several industrial exposures have been evaluated for a causal association with brain tumor formation but the results are inconclusive. A casual association between the common mutagens of tobacco, alcohol, or dietary factors has not yet been established. There is no clear evidence that the incidence of brain tumors has changed over time. This article presents the descriptive epidemiology of the commonest brain tumors of children and adults.

  18. Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins.

    PubMed

    Keating, Jane J; Okusanya, Olugbenga T; De Jesus, Elizabeth; Judy, Ryan; Jiang, Jack; Deshpande, Charuhas; Nie, Shuming; Low, Philip; Singhal, Sunil

    2016-04-01

    During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection. Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in three humans with lung adenocarcinoma. The peak tumor-to-background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 h and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30% of mice with positive margins. Molecular imaging identified an additional 50% of residual tumor deposits (p < 0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5. Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection.

  19. Probe-guided surgery for colorectal cancer.

    PubMed

    Lechner, P; Lind, P; Snyder, M; Haushofer, H

    2000-01-01

    Anti-CEA-scintigraphy turned out to be very reliable in detecting primary and recurrent colorectal cancer, its overall accuracy being more than 90%. The intraoperative application of this technology should provide similar results when focussing at extrahepatic tumor deposits, for example in lymph nodes, thus allowing accurate staging of the underlying disease. To test this hypothesis we launched the following feasibility study the results of which are compared to those reported in the recent literature. We investigated 20 patients, six with rectum and 14 with colon cancer. 24 hours before surgery they were intravenously given 1 ml of a fab'-fragment-antibody to CEA, labeled with 25 mCi of 99mTc (CEA-Scan). During surgery the radioactivity in lymph glands regional to the tumors was measured and compared to the much lower activity in healthy nodes. For this we used a scintillation probe (C-Trak, Care Wise, Inc., Morgan Hill, CA). All lymph nodes of interest were then excised and submitted to frozen section pathology. In 7 out of 20 cases scintimetry led to an up-staging of the disease. In addition we found metastatic spread to lymph nodes that were basically not regional to the primary tumor (retroperitoneum, renal hilum etc.). Scintimetry can precisely identify even very small tumor deposits. So it leads to accurate staging while surgery is still ongoing. In a further step the concept of sentinel node diagnosis, which is right now being clinically evaluated, may some day be applied in colorectal surgical oncology.

  20. Hypoxia in Microscopic Tumors

    PubMed Central

    Li, Xiao-Feng; O’Donoghue, Joseph A

    2008-01-01

    Tumor hypoxia has been commonly observed in a broad spectrum of primary solid malignancies. Hypoxia is associated with tumor progression, increased aggressiveness, enhanced metastatic potential and poor prognosis. Hypoxic tumor cells are resistant to radiotherapy and some forms of chemotherapy. Using an animal model, we recently showed that microscopic tumors less than 1 mm diameter were severely hypoxic. In this review, models and techniques for the study of hypoxia in microscopic tumors are discussed. PMID:18384940

  1. 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.

  2. 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.

  3. Theranostic imaging of liver cancer using targeted optical/MRI dual-modal probes

    PubMed Central

    Zeng, Chaoting; Wang, Kun; Liang, Xiaoyuan; Chi, Chongwei; Liang, Xiao; Yang, Jian; Fang, Chihua; Tian, Jie

    2017-01-01

    The accurate preoperative detection and intraoperative navigation afforded by imaging techniques have had significant impact on the success of liver cancer surgeries. However, it is difficult to achieve satisfactory performance in both diagnosis and surgical treatment processes using any single modality imaging method. Here, we report the synthesis and characteristics of a novel dual-modality magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) probe and verify its feasibility in nude mouse models with liver cancer. The probes are comprised of superparamagnetic iron oxide (SPIO) nanoparticles coated with liposomes to which a tumor-targeted agent, Arg-Gly-Asp peptides (RGD), and a NIRF dye (indocyanine green, ICG) have been conjugated. Specific targeting, biodistribution, and the imaging ability of the probes for MRI-NIRF were examined. Furthermore, we applied the dual-modality methodology toward the preoperative diagnosis and intraoperative guidance of radical resection in mouse models with both orthotopic liver tumors and intrahepatic tumor metastasis. The study demonstrated that both MRI and fluorescent images showed clear tumor delineation after probe injection (SPIO@Liposome-ICG-RGD). The contrast-to-noise ratio obtained from MRI was 31.9 ± 25.4 at post-injection for the preoperative diagnosis, which is helpful for detecting small tumors (0.9 ± 0.5 mm). The maximum tumor to background ratio of NIRF imaging was 2.5 ± 0.3 at 72 h post-injection for effectively capturing miniscule tumor lesions (0.6 ± 0.3 mm) intraoperatively. The novel MRI-NIRF dual modality probes are promising for the achievement of more accurate liver tumor detection and resection. PMID:28416757

  4. 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.

  5. The Antartic Ice Borehole Probe

    NASA Technical Reports Server (NTRS)

    Behar, A.; Carsey, F.; Lane, A.; Engelhardt, H.

    2000-01-01

    The Antartic Ice Borehole Probe mission is a glaciological investigation, scheduled for November 2000-2001, that will place a probe in a hot-water drilled hole in the West Antartic ice sheet. The objectives of the probe are to observe ice-bed interactions with a downward looking camera, and ice inclusions and structure, including hypothesized ice accretion, with a side-looking camera.

  6. 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.

  7. 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

    2012-04-03

    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.

  8. 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.

  9. 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.

  10. Passive tumor targeting and imaging by using mercaptosuccinic acid-coated near-infrared quantum dots

    PubMed Central

    Lin, Guimiao; Wang, Xiaomei; Yin, Feng; Yong, Ken-Tye

    2015-01-01

    In this paper, we demonstrate the preparation of monodispersed quantum dots (QDs) as near-infrared (NIR) optical probes for in vivo pancreatic cancer targeting and imaging. The design of these luminescent probes involves functionalizing NIR QDs with ligand mercaptosuccinic acid (MSA), which targets the tumor site by enhanced permeability and retention effect. The colloidal and optical stability of the QDs can be maintained for >1 week. In vivo optical imaging studies in nude mice bearing pancreatic tumor show that the probes accumulate at tumor sites for >2.5 hours following intravenous injection of the functionalized NIR QDs. Tumor-labeling studies showed no evidence of harmful effects on the treated animals, even at a dose as high a ~50 mg/kg. These results demonstrate that the engineered MSA-functionalized QDs can serve as a diagnostic platform for early detection of cancer, as well as in image-guided precise surgical resection of tumors. PMID:25609948

  11. Freehand 3D ultrasound breast tumor segmentation

    NASA Astrophysics Data System (ADS)

    Liu, Qi; Ge, Yinan; Ou, Yue; Cao, Biao

    2007-12-01

    It is very important for physicians to accurately determine breast tumor location, size and shape in ultrasound image. The precision of breast tumor volume quantification relies on the accurate segmentation of the images. Given the known location and orientation of the ultrasound probe, We propose using freehand three dimensional (3D) ultrasound to acquire original images of the breast tumor and the surrounding tissues in real-time, after preprocessing with anisotropic diffusion filtering, the segmentation operation is performed slice by slice based on the level set method in the image stack. For the segmentation on each slice, the user can adjust the parameters to fit the requirement in the specified image in order to get the satisfied result. By the quantification procedure, the user can know the tumor size varying in different images in the stack. Surface rendering and interpolation are used to reconstruct the 3D breast tumor image. And the breast volume is constructed by the segmented contours in the stack of images. After the segmentation, the volume of the breast tumor in the 3D image data can be obtained.

  12. Nondestructive Test Probe

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Under the Aircraft Structural Integrity program, Langley Research Center invented a device to detect fatigue cracks in aluminum alloy plates. Krautkramer Branson obtained an exclusive license and commercialized a hand-held device, the "CrackFinder," an electromagnetic probe for nondestructive evaluation, used to scan aircraft skins for surface breaks. The technology involves an eddy current, which is an electrical current induced by an alternating magnetic field. The CrackFinder also employs an innovative self-nulling feature, where the device automatically recalibrates to zero so that each flaw detected produces a reading. Compared to conventional testing systems, the CrackFinder is affordable, small, simple to use, and needs no calibration.

  13. 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.

  14. Simpson Probe Lab Test

    NASA Technical Reports Server (NTRS)

    1994-01-01

    In order to study the fatigue processes of aerospace materials it is necessary to perform controlled experiments on the crack growth rates and number of fatigue cycles to failure under specific loading conditions. The photo shows an aluminum compact tension specimen installed in a hydraulic load frame. The load frame is used to apply well defined cyclic stresses to the sample under test. Also mounted on the load frame is the Langley developed automated fatigue crack tip tracing system. The system incorporates the Self-Nulling Eddy Current Probe and a two-axis scanner in order to locate the position of the fatigue crack tip in the sample. The position of the crack tip is continuously updated as the fatigue process continues. The system is fully automated, with the ability to update loading parameters based on crack tip position while compiling a complete history of crack tip position versus fatigue cycles.

  15. Solar Probe Plus

    NASA Technical Reports Server (NTRS)

    Szabo, Adam

    2011-01-01

    The NASA Solar Probe Plus mission is planned to be launched in 2018 to study the upper solar corona with both.in-situ and remote sensing instrumentation. The mission will utilize 6 Venus gravity assist maneuver to gradually lower its perihelion to 9.5 Rs below the expected Alfven pOint to study the sub-alfvenic solar wind that is still at least partially co-rotates with the Sun. The detailed science objectives of this mission will be discussed. SPP will have a strong synergy with The ESA/NASA Solar orbiter mission to be launched a year ahead. Both missions will focus on the inner heliosphere and will have complimentary instrumentations. Strategies to exploit this synergy will be also presented.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Tumor macroenvironment and metabolism.

    PubMed

    Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-04-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described.

  1. Prospective comparison of 3 gamma-probes for sentinel lymph node detection in 200 breast cancer patients.

    PubMed

    Classe, Jean-Marc; Fiche, Maryse; Rousseau, Caroline; Sagan, Christine; Dravet, François; Pioud, Raphaëlle; Lisbona, Albert; Ferrer, Ludovic; Campion, Loic; Resche, Isabelle; Curtet, Chantal

    2005-03-01

    Previous reports have shown that axillary sentinel lymph node (ASLN) radiodetection allows accurate axillary staging for patients with early breast cancer. Radioguided surgery implies the use of a gamma-probe to count the emitted radioactivity of marked ASLNs. Several gamma-probes are commercially available, each with its own properties. The clinical impact of the type of gamma-probe used for ASLN radiodetection remains to be evaluated. Three commercially available gamma-probes were evaluated: a scintillator with a bismuth germanate crystal (probe A), a semiconductor with a cadmium telluride crystal (probe B), and a semiconductor with a cadmium zinc telluride crystal (probe C). Two hundred patients with early breast cancer were prospectively enrolled to undergo ASLN radiodetection and axillary lymphadenectomy. ASLN mapping consisted of injecting (99m)Tc-sulfur-colloid around the tumor. For each patient, sentinel lymph nodes were counted successively with the 3 probes and the sensitivity of each gamma-probe was determined from ASLN residual activity. The results of detection rates and false-negative rates for each probe were compared. Mean residual ASLN activity was 52 kBq (range, 0.07-189 kBq). Sensitivity was compared among the 3 probes and found to be best for probe A. The detection rate of probe A was significantly better than that of probe B (93% vs. 86%, P = 0.05) but not different from that of probe C (93% vs. 90%). No differences in false-negative rates were observed among the 3 probes. ASLN detection rate depends on the type of gamma-probe used. Because failure to detect the ASLN leads to complete axillary lymphadenectomy, involving local morbidity and other sequelae, the type of gamma-probe must be considered important for sentinel lymph node radiodetection.

  2. 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

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

    PubMed

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

    2016-09-26

    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.

  4. Posterior Fossa Tumors.

    PubMed

    Brandão, Lara A; Young Poussaint, Tina

    2017-02-01

    Pediatric brain tumors are the leading cause of death from solid tumors in childhood. The most common posterior fossa tumors in children are medulloblastoma, atypical teratoid/rhabdoid tumor, cerebellar pilocytic astrocytoma, ependymoma, and brainstem glioma. Location, and imaging findings on computed tomography (CT) and conventional MR (cMR) imaging may provide important clues to the most likely diagnosis. Moreover, information obtained from advanced MR imaging techniques increase diagnostic confidence and help distinguish between different histologic tumor types. Here we discuss the most common posterior fossa tumors in children, including typical imaging findings on CT, cMR imaging, and advanced MR imaging studies.

  5. Krukenberg tumor with yolk sac tumor differentiation.

    PubMed

    Zamecnik, Michal; Voltr, Lubomir; Stuk, Jan; Chlumska, Alena

    2008-04-01

    An unusual case of bilateral Krukenberg tumor with foci of yolk sac tumor (YST) differentiation occurring in a 50-year-old patient is reported. The primary tumor was in the gastric antrum, and it showed morphology of poorly differentiated adenocarcinoma with diffuse and solid growth pattern. A component of typical YST was not found in the gastric primary and lymph node metastases, although some cells in these locations were positive for alpha-fetoprotein. In the ovarian metastases, YST element showed microcystic/reticular and solid patterns, whereas the adenocarcinoma component was of diffuse type with signet ring cells and with some undifferentiated areas. The case represents further example of the somatic cell-derived tumor with focal germ cell-type differentiation and the first report of YST differentiation in Krukenberg tumor.

  6. Classification of tumor markers.

    PubMed

    Suresh, M R

    1996-01-01

    Since the discovery of the first tumor markers more than a century ago (Bence-Jones proteins), a vast array of molecules have been described as being associated with cancer. These are generally naturally occurring biomolecules with the exception of neo-antigens expressed in certain tumors induced by viruses. Tumor markers can be broadly classified into tumor specific antigens and tumor-associated markers. Most tumor markers were often heralded as highly tumor specific but subsequent studies demonstrated their presence in normal tissues of the adult or in various stages of ontogeny. As a result, very few tumor-specific antigens can be recognized. The idiotypes of immunoglobulins of B cell tumors and certain neo-antigens of virus induced tumors are two examples that are strictly tumor specific. The vast majority of tumor markers are in reality tumor-associated antigens and can be classified into two types based on their size. The low-molecular weight tumor markers (approximately < 1000 Daltons) include some nucleosides, lipid associated sialic acid, polyamines, pseudouridine, pigment derivatives, and other metabolites. The macromolecular tumor antigens are the most important sub-type useful in the clinical management of cancer patients. The large cancer antigens are either enzymes, growth factors, hormones, receptors, biological response modifiers, oncogenes and their products, or glycoconjugates which include glycoproteins and glycolipids. Collectively all the commercial tumor marker assays available to the oncologist for cancer patient management amount to an annual sales of > $1 billion world wide. The demonstrated clinical usefulness and commercial success of tumor markers have continued to fuel exciting research into the discovery and novel uses of new analytes.

  7. 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.

  8. 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.

  9. 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.

  10. Nanobits: customizable scanning probe tips

    NASA Astrophysics Data System (ADS)

    Rajendra Kumar, R. T.; Hassan, S. U.; Sardan Sukas, O.; Eichhorn, V.; Krohs, F.; Fatikow, S.; Boggild, P.

    2009-09-01

    We present here a proof-of-principle study of scanning probe tips defined by planar nanolithography and integrated with AFM probes using nanomanipulation. The so-called 'nanobits' are 2-4 µm long and 120-150 nm thin flakes of Si3N4 or SiO2, fabricated by electron beam lithography and standard silicon processing. Using a microgripper they were detached from an array and fixed to a standard pyramidal AFM probe or alternatively inserted into a tipless cantilever equipped with a narrow slit. The nanobit-enhanced probes were used for imaging of deep trenches, without visible deformation, wear or dislocation of the tips of the nanobit after several scans. This approach allows an unprecedented freedom in adapting the shape and size of scanning probe tips to the surface topology or to the specific application.

  11. Nanobits: customizable scanning probe tips.

    PubMed

    Rajendra Kumar, R T; Hassan, S U; Sardan Sukas, O; Eichhorn, V; Krohs, F; Fatikow, S; Boggild, P

    2009-09-30

    We present here a proof-of-principle study of scanning probe tips defined by planar nanolithography and integrated with AFM probes using nanomanipulation. The so-called 'nanobits' are 2-4 microm long and 120-150 nm thin flakes of Si(3)N(4) or SiO(2), fabricated by electron beam lithography and standard silicon processing. Using a microgripper they were detached from an array and fixed to a standard pyramidal AFM probe or alternatively inserted into a tipless cantilever equipped with a narrow slit. The nanobit-enhanced probes were used for imaging of deep trenches, without visible deformation, wear or dislocation of the tips of the nanobit after several scans. This approach allows an unprecedented freedom in adapting the shape and size of scanning probe tips to the surface topology or to the specific application.

  12. 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.

  13. New chemical probe technologies: applications to imaging and drug discovery (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Bogyo, Matthew

    2017-02-01

    Proteases are enzymes that play pathogenic roles in many common human diseases such as cancer, asthma, arthritis, atherosclerosis and infection by pathogens. Tools to dynamically monitor their activity can be used as diagnostic agents, as imaging contrast agents for intra-operative image guidance and for the identification of novel classes of protease-targeted drugs. I will describe our efforts to design and synthesize small molecule probes that produce a fluorescent signal upon binding to a protease target. We have identified probes that show tumor-specific retention, fast activation kinetics, and rapid systemic distribution making them useful for real-time fluorescence guided tumor resection and other diagnostic imaging applications.

  14. Intra-operative probe for brain cancer: feasibility study

    NASA Astrophysics Data System (ADS)

    Vu Thi, M. H.; Charon, Y.; Duval, M. A.; Lefebvre, F.; Menard, L.; Pitre, S.; Pinot, L.; Siebert, R.

    2007-07-01

    The present work aims a new medical probe for surgeons devoted to brain cancers, in particular glioblastoma multiforme. Within the last years, our group has started the development of a new intra-operative beta imaging probe. More recently, we took an alternative approach for the same application: a fluorescence probe. In both cases the purpose is to differentiate normal from tumor brain tissue. In a first step, we developed set-ups capable to measure autofluorescence. They are based on a dedicated epi-fluorescence design and on specific fiber optic probes. Relative signal amplitude, spectral shape and fluorescence lifetime measurements are foreseen to distinguish normal and cancer tissue by analyzing fluorophores like NADH, lipopigments and porphyrines. The autofluorescence spectra are recorded in the 460-640 nm range with a low resolution spectrometer. For lifetime measurements a fast detector (APD) is used together with a TCSPC-carte. Intrinsic wavelength- and time-resolutions are a few nm and 200 ps, respectively. Different samples have been analyzed to validate our new detection system and to allow a first configuration of our medical fluorescence probe. First results from the tissue measurements are shown.

  15. 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.

  16. Brain Tumor Surgery

    MedlinePlus

    ... Proton Therapy Alternative & Integrative Medicine Clinical Trials GBM AGILE TTFields – Optune™ Brain Tumor Treatment Locations Treatment Side ... Proton Therapy Alternative & Integrative Medicine Clinical Trials GBM AGILE TTFields – Optune™ Brain Tumor Treatment Locations Treatment Side ...

  17. Posterior fossa tumor

    MedlinePlus

    ... and the tumor can easily press on delicate structures if it grows. Depending on the type and size of the tumor, radiation treatment may also be used after surgery. Support Groups You can ease the stress of illness ...

  18. 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

  19. American Brain Tumor Association

    MedlinePlus

    ... Molecule Read More ABTA News April 6, 2017 Chicago-Based American Brain Tumor Association’s Breakthrough for Brain ... Association 8550 W. Bryn Mawr Ave. Ste 550 Chicago, IL 60631 © 2014 American Brain Tumor Association Phone: ...

  20. Lacrimal gland tumor

    MedlinePlus

    ... B. Lacrimal gland tumors. In: Tasman W, Jaeger EA, eds. Duane's Ophthalmology . 16th ed. Philadelphia, PA: Lippincott ... JA. Secondary orbital tumors. In: Tasman W, Jaeger EA, eds. Duane's Ophthalmology . 16th ed. Philadelphia, PA: Lippincott ...

  1. Gastric stromal tumor.

    PubMed

    Ovali, Gülgün Yilmaz; Tarhan, Serdar; Serter, Selim; Pabuşçu, Yüksel

    2005-06-01

    Gastric stromal tumors are rare neoplasms of the stomach. In this report we present a gastric stromal tumor with an exophytic growth pattern, and describe magnetic resonance imaging and endoscopic ultrasonography findings.

  2. 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, ...

  3. Renal primitive neuroectodermal tumors.

    PubMed

    Bartholow, Tanner; Parwani, Anil

    2012-06-01

    Primitive neuroectodermal tumors exist as a part of the Ewing sarcoma/primitive neuroectodermal tumor family. These tumors most commonly arise in the chest wall and paraspinal regions; cases with a renal origin are rare entities, but have become increasingly reported in recent years. Although such cases occur across a wide age distribution, the average age for a patient with a renal primitive neuroectodermal tumor is the mid- to late 20s, with both males and females susceptible. Histologically, these tumors are characterized by pseudorosettes. Immunohistochemically, CD99 is an important diagnostic marker. Clinically, these are aggressive tumors, with an average 5-year disease-free survival rate of only 45% to 55%. Given that renal primitive neuroectodermal tumor bears many similarities to other renal tumors, it is important to review the histologic features, immunostaining profile, and genetic abnormalities that can be used for its correct diagnosis.

  4. Pancreatic islet cell tumor

    MedlinePlus

    ... functions. These include blood sugar level and the production of stomach acid. Tumors that arise from islet ... try and shrink the tumors. If the abnormal production of hormones is causing symptoms, you may receive ...

  5. 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.

  6. 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.

  7. Transient Astrophysics Probe

    NASA Astrophysics Data System (ADS)

    Camp, Jordan

    2017-08-01

    Transient Astrophysics Probe (TAP), selected by NASA for a funded Concept Study, is a wide-field high-energy transient mission proposed for flight starting in the late 2020s. TAP’s main science goals, called out as Frontier Discovery areas in the 2010 Decadal Survey, are time-domain astrophysics and counterparts of gravitational wave (GW) detections. The mission instruments include unique imaging soft X-ray optics that allow ~500 deg2 FoV in each of four separate modules; a high sensitivity, 1 deg2 FoV soft X-ray telescope based on single crystal silicon optics; a passively cooled, 1 deg2 FoV Infrared telescope with bandpass 0.6-3 micron; and a set of ~8 small NaI gamma-ray detectors. TAP will observe many events per year of X-ray transients related to compact objects, including tidal disruptions of stars, supernova shock breakouts, neutron star bursts and superbursts, and high redshift Gamma-Ray Bursts. Perhaps most exciting is TAP’s capability to observe X-ray and IR counterparts of GWs involving stellar mass black holes detected by LIGO/Virgo, and possibly X-ray counterparts of GWs from supermassive black holes, detected by LISA and Pulsar Timing Arrays.

  8. 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).

  9. Active Dynamic Frictional Probes

    NASA Astrophysics Data System (ADS)

    Steimel, Joshua; Aragones, Juan; Alexander-Katz, Alfredo

    2015-03-01

    In biological systems there are a myriad of interactions occurring instantaneously and these interactions can vary drastically in the strength of the interaction, the speed at which this interaction occurs, and the duration of the interaction. When multiple interactions occur any of these factors can determine which particular interaction is dominant. However, currently it is extremely difficult to measure binding affinity, Kon, and Koff rates in a relatively high throughput manner. Here we propose a novel and versatile system that will be able to detect differences in binding affinity of wide range of transient interactions and will be able to extract the relevant time scales of these interactions. Our system will utilize ferromagnetic particles that can be easily functionalized with a receptor of interest and the substrate will be coated in the corresponding ligand. A rotating magnetic field will cause particles, henceforth referred to as rollers, to rotate and this rotational motion will be converted into translational motion via the effective frictional force induced by interaction that is being probed. By measuring the translation of the rollers to a baseline, where only hydrodynamic friction occurs, we can measure the relative strength of the interactions. We can also potentially measure kinetic information by changing the frequency at which the magnetic field rotates, since changing the frequency at which the bead rotates is akin to changing the time allowed for bond formation. We will measure a wide range of interaction including ionic, metal-ion coordination, IgG-Protein A complex, and biotin-streptavidin complex.

  10. 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).

  11. Optically Measured Microvascular Blood Flow Contrast of Malignant Breast Tumors

    PubMed Central

    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

  12. Liver Tumors (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Liver Tumors KidsHealth > For Parents > Liver Tumors Print A A A What's in this ... Malignant (Cancerous) Tumors Symptoms Diagnosis Treatment Coping The liver is the body's largest solid organ. Lying next ...

  13. Tracing the Tumor Lineage

    PubMed Central

    Navin, Nicholas E.; Hicks, James

    2010-01-01

    Defining the pathways through which tumors progress is critical to our understanding and treatment of cancer. We do not routinely sample patients at multiple time points during the progression of their disease, and thus our research is limited to inferring progression a posteriori from the examination of a single tumor sample. Despite this limitation, inferring progression is possible because the tumor genome contains a natural history of the mutations that occur during the formation of the tumor mass. There are two approaches to reconstructing a lineage of progression: (1) inter-tumor comparisons, and (2) intra-tumor comparisons. The inter-tumor approach consists of taking single samples from large collections of tumors and comparing the complexity of the genomes to identify early and late mutations. The intra-tumor approach involves taking multiple samples from individual heterogeneous tumors to compare divergent clones and reconstruct a phylogenetic lineage. Here we discuss how these approaches can be used to interpret the current models for tumor progression. We also compare data from primary and metastatic copy number profiles to shed light on the final steps of breast cancer progression. Finally, we discuss how recent technical advances in single cell genomics will herald a new era in understanding the fundamental basis of tumor heterogeneity and progression. PMID:20537601

  14. Hepatic tumor ablation.

    PubMed

    Sindram, David; Lau, Kwan N; Martinie, John B; Iannitti, David A

    2010-08-01

    Ablation of liver tumors is part of a multimodality liver-directed strategy in the treatment of various tumors. The goal of ablation is complete tumor destruction, and ultimately improvement of quality and quantity of life for the patient. Technology is evolving rapidly, with important improvements in efficacy. The current state of ablation technology and indications for ablation are described in this review.

  15. Malignant tumors of childhood

    SciTech Connect

    Brooks, B.J.

    1986-01-01

    This book contains 34 papers about malignant tumors. some of the titles are: Invasive Cogenital Mesoblastic Nephroma, Leukemia Update, Unusual Perinatal Neoplasms, Lymphoma Update, Gonadal Germ Cell Tumors in Children, Nutritional Status and Cancer of Childhood, and Chemotherapy of Brain tumors in Children.

  16. Magnetic resonance imaging of tumor with a self-traceable phosphorylcholine polymer.

    PubMed

    Yamada, Hisatsugu; Hasegawa, Yoshinori; Imai, Hirohiko; Takayama, Yuki; Sugihara, Fuminori; Matsuda, Tetsuya; Tochio, Hidehito; Shirakawa, Masahiro; Sando, Shinsuke; Kimura, Yu; Toshimitsu, Akio; Aoyama, Yasuhiro; Kondo, Teruyuki

    2015-01-21

    Polymers are concentration-amplified with respect to the monomeric units. We show here that a phosphorylcholine polymer enriched with (13)C/(15)N at the methyl groups is self-traceable by multiple-resonance (heteronuclear-correlation) NMR in tumor-bearing mice inoculated with the mouse rectal cancer cell line (colon 26). Preliminary measurements indicated that the present polymeric nanoprobe was satisfactorily distinguished from lipids and detectable with far sub-micromolar spectroscopic and far sub-millimolar imaging sensitivities. Detailed ex vivo and in vivo studies for the tumor-bearing mice administered the probe with a mean molecular weight of 63,000 and a mean size of 13 nm, revealed the following: (1) this probe accumulates in the tumor highly selectively (besides renal excretion) and efficiently (up to 30% of the injected dose), (2) the tumor can thus be clearly in vivo imaged, the lowest clearly imageable dose of the probe being 100 mg/kg or 2.0 mg/20-g mouse, and (3) the competition between renal excretion and tumor accumulation is size-controlled; that is, the larger (higher molecular-weight) and smaller (lower molecular-weight) portions of the probe undergo tumor accumulation and renal excretion, respectively. The observed size dependence suggests that the efficient tumor-targeting of the present probe is stimulated primarily by the so-called enhanced permeability and retention (EPR) effect, that is, size-allowed invasion of the probe into the tumor tissue via defective vascular wall. Self-traceable polymers thus open an important area of magnetic resonance imaging (MRI) of tumors and may provide a highly potential tool to visualize various delivery/localization processes using synthetic polymers.

  17. STM-SQUID probe microscope

    NASA Astrophysics Data System (ADS)

    Hayashi, Tadayuki; Tachiki, Minoru; Itozaki, Hideo

    2007-11-01

    We have developed a STM-SQUID probe microscope. A high TC SQUID probe microscope was combined with a scanning tunneling microscope for investigation of samples at room temperature in air. A high permeability probe needle was used as a magnetic flux guide to improve the spatial resolution. The probe with tip radius of less than 100 nm was prepared by microelectropolishing. The probe was also used as a scanning tunneling microscope tip. Topography of the sample surface could be measured by the scanning tunneling microscope with high spatial resolution prior to observation by SQUID microscopy. The SQUID probe microscope image could be observed while keeping the distance from the sample surface to the probe tip constant. We observed a topographic image and a magnetic image of Ni fine pattern and also a magnetically recorded hard disk. Furthermore we have investigated a sample vibration method of the static magnetic field emanating from a sample with the aim of achieving a higher signal-to-noise (S/N) ratio.

  18. 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.

  19. An OFF-ON Two-Photon Fluorescent Probe for Tracking Cell Senescence in Vivo.

    PubMed

    Lozano-Torres, Beatriz; Galiana, Irene; Rovira, Miguel; Garrido, Eva; Chaib, Selim; Bernardos, Andrea; Muñoz-Espín, Daniel; Serrano, Manuel; Martínez-Máñez, Ramón; Sancenón, Félix

    2017-07-05

    A naphthalimide-based two-photon probe (AHGa) for the detection of cell senescence is designed. The probe contains a naphthalimide core, an l-histidine methyl ester linker, and an acetylated galactose bonded to one of the aromatic nitrogen atoms of the l-histidine through a hydrolyzable N-glycosidic bond. Probe AHGa is transformed into AH in senescent cells resulting in an enhanced fluorescent emission intensity. In vivo detection of senescence is validated in mice bearing tumor xenografts treated with senescence-inducing chemotherapy.

  20. Assessment of tumor response to tyrosine kinase inhibitors

    PubMed Central

    Lowery, Amanda; Han, Zhaozhong

    2015-01-01

    This review briefly summarizes recent developments in the use of non-invasive imaging to assess tumor response to TKI therapy. Receptor tyrosine kinases play important roles in cancer development. A new class of drugs, tyrosine kinase inhibitors (TKI) can induce rapid and dramatic tumor suppression when administered to carefully selected patient groups. Identifying these patients with responding tumors prior to or shortly after the initiation of therapy remains challenging. The gold standard of response assessment has been by invasive biopsies used in biological and biochemical procedures. Advances in non-invasive imaging at the anatomical, functional and molecular level have enabled the early detection of tumor response; sometimes within days of beginning treatment. The growing area of molecular imaging has spurred the discovery of novel targeting peptides to bind TKI responding tumors. The emergence of targeted, quick responding imaging probes advances the field of cancer management towards the goal of personalized medicine. PMID:21622159

  1. Neonatal solid tumors.

    PubMed

    Chandrasekaran, Aravindan

    2017-07-11

    Neonatal tumors are different from tumors of the older children and knowledge gained from treating older children can not be extrapolated to neonates. Neonates have immature physiology and their haematopoietic and immune systems are not fully developed and the response to therapy is unpredictable. Hence it is imperative to study these tumors as separate entity. The aim of this study is to analyse this rare set of tumors in terms of their incidence, clinical features and management. All babies admitted in our hospital with tumors from January, 2011 to January 2016 were studied. Tumor-like conditions like haemangioma, lymphangioma and hamartomas were included. The age, sex distribution, type of tumor and management were studied. A total of 51 cases were registered out of which, 29 cases were haemangiomas and lymphangiomas. Of remaining 20 cases, 5 were benign ovarian cysts, 3 were neuroblastomas, 3 were congenital fibrosarcomas, 3 were sacrococcygeal teratomas. Wilm's tumor, congenital mesoblastic nephroma, haemangioendothelioma of liver and others formed the remaining six cases. Our study insists that the neonatal tumors are distinct subset of pediatric tumors, requiring careful selection of treatment modalities and most of the solid tumors can be successfully managed if diagnosed and treated early. Neonatal tumors are defined as tumors which are diagnosed before the first month of life. Some of them can be congenital (present at birth). Neonatal tumors are different from tumors in older children in terms of etiopathogenesis, behavior and response to therapy as well as long-term outcomes. Copyright © 2017. Published by Elsevier B.V.

  2. 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.

  3. 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).

  4. Integrated microfluidic probe station.

    PubMed

    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.

  5. 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.

  6. Subminiature Hot-Wire Probes

    NASA Technical Reports Server (NTRS)

    Westphal, R. V.; Lemos, F. R.; Ligrani, P. M.

    1989-01-01

    Class of improved subminiature hot-wire flow-measuring probes developed. Smaller sizes yield improved resolution in measurements of practical aerodynamic flows. Probe made in one-wire, two-perpendicular-wire, and three-perpendicular-wire version for measurement of one, two, or all three components of flow. Oriented and positioned on micromanipulator stage and viewed under microscope during fabrication. Tested by taking measurements in constant-pressure turbulent boundary layer. New probes give improved measurements of turbulence quantities near surfaces and anisotropies of flows strongly influence relative errors caused by phenomena related to spatial resolution.

  7. Optic probe for semiconductor characterization

    DOEpatents

    Sopori, Bhushan L [Denver, CO; Hambarian, Artak [Yerevan, AM

    2008-09-02

    Described herein is an optical probe (120) for use in characterizing surface defects in wafers, such as semiconductor wafers. The optical probe (120) detects laser light reflected from the surface (124) of the wafer (106) within various ranges of angles. Characteristics of defects in the surface (124) of the wafer (106) are determined based on the amount of reflected laser light detected in each of the ranges of angles. Additionally, a wafer characterization system (100) is described that includes the described optical probe (120).

  8. Atmospheric probes: needs and prospects

    NASA Astrophysics Data System (ADS)

    Owen, Tobias

    2004-02-01

    There is only one Rosetta Stone in the Solar System; it's in the British Museum. We cannot understand the inner planets by simply studying the Earth, nor can we apprehend the giants by examining only Jupiter. Despite the stunning successes of previous probes to Venus and the Galileo probe to Jupiter, our knowledge of the atmospheres of even these two planets remains tantalizingly incomplete. We must therefore return to Venus and consider the challenge of exploring all of the outer planets with a family of identical probes, a project that could commemorater the vision of multiple worlds championed by Giordano Bruno.

  9. 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

  10. 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.

  11. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Self-assembled gold nanoparticle molecular probes for detecting proteolytic activity in vivo

    PubMed Central

    Mu, C. Jenny; LaVan, David A.; Langer, Robert S.; Zetter, Bruce R.

    2010-01-01

    Target-activatable fluorogenic probes based on gold nanoparticles (AuNPs) functionalized with self-assembled heterogeneous monolayers of dye-labeled peptides and poly(ethylene glycol) have been developed to visualize proteolytic activity in vivo. A one-step synthesis strategy that allows simple generation of surface defined AuNP probe libraries is presented as a means of tailoring and evaluating probe characteristics for maximal fluorescence enhancement after protease activation. Optimal AuNP probes targeted to trypsin and urokinase-type plasminogen activator required the incorporation of a dark quencher to achieve 5 to 8-fold signal amplification. These probes exhibited extended circulation time in vivo and high image contrast in a mouse tumor model. PMID:20146506

  13. 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

  14. Imagery of pineal tumors.

    PubMed

    Deiana, G; Mottolese, C; Hermier, M; Louis-Tisserand, G; Berthezene, Y

    2015-01-01

    Pineal tumors are rare and include a large variety of entities. Germ cell tumors are relatively frequent and often secreting lesions. Pineal parenchymal tumors include pineocytomas, pineal parenchymal tumor of intermediate differentiation, pineoblastomas and papillary tumors of the pineal region. Other lesions including astrocytomas and meningiomas as well as congenital malformations i.e. benign cysts, lipomas, epidermoid and dermoid cysts, which can also arise from the pineal region. Imagery is often non-specific but detailed analysis of the images compared with the hormone profile can narrow the spectrum of possible diagnosis.

  15. Tumor Endothelial Cells

    PubMed Central

    Dudley, Andrew C.

    2012-01-01

    The vascular endothelium is a dynamic cellular “organ” that controls passage of nutrients into tissues, maintains the flow of blood, and regulates the trafficking of leukocytes. In tumors, factors such as hypoxia and chronic growth factor stimulation result in endothelial dysfunction. For example, tumor blood vessels have irregular diameters; they are fragile, leaky, and blood flow is abnormal. There is now good evidence that these abnormalities in the tumor endothelium contribute to tumor growth and metastasis. Thus, determining the biological basis underlying these abnormalities is critical for understanding the pathophysiology of tumor progression and facilitating the design and delivery of effective antiangiogenic therapies. PMID:22393533

  16. Immunology of brain tumors.

    PubMed

    Roth, Patrick; Eisele, Günter; Weller, Michael

    2012-01-01

    Brain tumors of different origin, but notably malignant gliomas, are characterized by their immunosuppressive properties which allow them to escape the host's immune surveillance. The activating immune cell ligands that are expressed by tumor cells, together with potentially immunogenic antigens, are overridden by numerous immune inhibitory signals, with TGF-3 as the master immunosuppressive molecule (Figure 4.1).The ongoing investigation of mechanisms of tumor-derived immunosuppression allows for an increasing understanding of brain tumor immunology. Targeting different mechanisms of tumor-derived immunosuppression, such as inhibition of TGF-[, may represent a promising strategy for future immunotherapeutic approaches.

  17. Ocular surface tumors

    PubMed Central

    Othman, Ihab Saad

    2009-01-01

    Tumors of the conjunctiva and cornea comprise a large and varied spectrum of conditions. These tumors are grouped into two major categories of congenital and acquired lesions. The acquired lesions are further subdivided based on origin of the mass into surface epithelial, mucoepidermoid, melanocytic, vascular, fibrous, neural, histiocytic, myxoid, myogenic, lipomatous, lymphoid, leukemic, metastatic and secondary tumors. Ocular surface tumors include a variety of neoplasms originating from squamous epithelium, melanocytic tumors and lymphocytic resident cells of the conjunctival stroma. In this review, we highlight clinical features of these lesions, important diagnostic and investigative tools and standard care of management. PMID:21234217

  18. A Novel Method for Imaging Apoptosis Using a Caspase-1 Near-Infrared Fluorescent Probe1

    PubMed Central

    Messerli, Shanta M; Prabhakar, Shilpa; Tang, Yi; Shah, Khalid; Cortes, Maria L; Murthy, Vidya; Weissleder, Ralph; Breakefield, Xandra O; Tung, Ching-Hsuan

    2004-01-01

    Abstract Here we describe a novel method for imaging apoptosis in cells using a near-infrared fluorescent (NIRF) probe selective for caspase-1 (interleukin 1β-converting enzyme, ICE). This biocompatible, optically quenched ICE-NIRF probe incorporates a peptide substrate, which can be selectively cleaved by caspase-1, resulting in the release of fluorescence signal. The specificity of this probe for caspase-1 is supported by various lines of evidence: 1) activation by purified caspase-1, but not another caspase in vitro; 2) activation of the probe by infection of cells with a herpes simplex virus amplicon vector (HGC-ICE-lacZ) expressing a catalytically active caspase-1-lacZ fusion protein; 3) inhibition of HGC-ICE-lacZ vector-induced activation of the probe by coincubation with the caspase-1 inhibitor YVAD-cmk, but not with a caspase-3 inhibitor; and 4) activation of the probe following standard methods of inducing apoptosis with staurosporine, ganciclovir, or ionizing radiation in culture. These results indicate that this novel ICE-NIRF probe can be used in monitoring endogenous and vector-expressed caspase-1 activity in cells. Furthermore, tumor implant experiments indicate that this ICE-NIRF probe can be used to detect caspase-1 activity in living animals. This novel ICE-NIRF probe should prove useful in monitoring endogenous and vector-expressed caspase-1 activity, and potentially apoptosis in cell culture and in vivo. PMID:15140398

  19. 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.

  20. 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.

  1. What Are Lung Carcinoid Tumors?

    MedlinePlus

    ... Carcinoid Tumor About Lung Carcinoid Tumors What Are Lung Carcinoid Tumors? Lung carcinoid tumors (also known as ... lungs, as well as the neuroendocrine system. The lungs The lungs are 2 sponge-like organs in ...

  2. 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

  3. Galectins in tumor angiogenesis

    PubMed Central

    Griffioen, Arjan W.

    2014-01-01

    The expansion of solid tumors depends on the continuous ingrowth of new blood vessels out of pre-existing capillaries. Consequently, tumor neovascularization or tumor angiogenesis is considered a hallmark of cancer and an attractive target for cancer therapy. Tumor angiogenesis is mainly carried out by endothelial cells (EC), i.e., the cells lining the luminal vessel wall. These cells have to take on different functional activities in order to successfully make new tumor blood vessels. In the last decade it has become apparent that galectins are important regulators of tumor angiogenesis. In the present review we summarize the current knowledge regarding the role galectins in tumor angiogenesis focussing on the endothelial galectins, i.e., gal-1/-3/-8/-9. PMID:25405165

  4. Nonfunctioning Juxtaglomerular Cell Tumor

    PubMed Central

    Sakata, Ryoko; Shimoyamada, Hiroaki; Yanagisawa, Masahiro; Murakami, Takayuki; Makiyama, Kazuhide; Nakaigawa, Noboru; Inayama, Yoshiaki; Ohashi, Kenichi; Nagashima, Yoji; Yao, Masahiro; Kubota, Yoshinobu

    2013-01-01

    The juxtaglomerular cell tumor (JGCT) is a rare renal tumor characterized by excessive renin secretion causing intractable hypertension and hypokalemia. However, asymptomatic nonfunctioning JGCT is extremely rare. Here, we report a case of nonfunctioning JGCT in a 31-year-old woman. The patient presented with a left renal tumor without hypertension or hypokalemia. Under a clinical diagnosis of renal cell carcinoma, radical nephrectomy was performed. The tumor was located in the middle portion adjacent to the renal pelvis, measuring 2 cm in size. Pathologically, the tumor was composed of cuboidal cells forming a solid arrangement, immunohistochemically positive for renin. Based on these findings, the tumor was diagnosed as JGCT. In cases with hyperreninism, preoperative diagnosis of JGCT is straightforward but difficult in nonfunctioning case. Generally, JGCT presents a benign biological behavior. Therefore, we should take nonfunctioning JGCT into the differential diagnoses for renal tumors, especially in younger patients to avoid excessive surgery. PMID:23607027

  5. Astrophysical probes of electromagnetic neutrinos

    NASA Astrophysics Data System (ADS)

    Giunti, Carlo; Kouzakov, Konstantin A.; Li, Yu-Feng; Lokhov, Alexey V.; Studenikin, Alexander I.; Zhou, Shun

    2017-09-01

    Electromagnetic properties of massive neutrinos and current best astrophysical bounds on neutrino magnetic moment and millicharge are outlined. Future probes of electromagnetic neutrinos from a core-collapse supernova with JUNO are discussed.

  6. The Radiation Belt Storm Probes

    NASA Image and Video Library

    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 ...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Comparative genomic analysis of tumors: detection of DNA losses and amplification.

    PubMed Central

    Lisitsyn, N A; Lisitsina, N M; Dalbagni, G; Barker, P; Sanchez, C A; Gnarra, J; Linehan, W M; Reid, B J; Wigler, M H

    1995-01-01

    We demonstrate the use of representational difference analysis for cloning probes that detect DNA loss and amplification in tumors. Using DNA isolated from human tumor cell lines to drive hybridization against matched normal DNA, we were able to identify six genomic regions that are homozygously deleted in cultured cancer cells. When this method was applied in the reverse way, using normal DNA to drive hybridization against tumor cell DNA, we readily isolated probes detecting amplification. Representational difference analysis was also performed on DNAs derived from tumor biopsies, and we thereby discovered a probe detecting very frequent homozygous loss in colon cancer cell lines and located on chromosome 3p. Images Fig. 1 Fig. 2 PMID:7816807

  14. The Interstellar Heliopause Probe

    NASA Astrophysics Data System (ADS)

    Lyngvi, A.; Falkner, P.; Peacock, A.

    The Interstellar Heliopause Probe (IHP) is one of four Technology Reference Missions (TRM) introduced by the Planetary Exploration Studies Section of the Science Payload & Advanced Concepts Office (SCI-A) at ESA. The overall purpose of the TRMs is to focus the development of strategically important technologies of likely relevance to future science missions. This is accomplished through the study of several technologically demanding and scientifically interesting missions, which are currently not part of the ESA science programme. The TRM baseline uses small satellites (< 200kg), with highly miniaturized and highly integrated payload suites. The motivation for this is to use low resource spacecraft in a phased approach, which will reduce the risk and cost, compared to a single, high resource mission. Equipped with a Highly Integrated Payload Suite (HIPS) the IHP will answer scientific questions concerning the nature of the interstellar medium, how the interstellar medium affects our solar system and how the solar system impacts the interstellar medium. The HIPS, which is a standard element in all TRMs miniaturize through resource reduction, by using miniaturized components and sensors, and by sharing common structures and payload functionality. To achieve the scientific requirements of the mission the spacecraft is to leave the solar system as close to the heliosphere nose as possible and reach a distance of 200 AU from the Sun within 25 years. The requirement of all TRMs is to use a Souyz-Fregat version 2B or equivalent low cost launch vehicle. With this constraint no current propulsion system is capable of delivering the necessary mass to the final destination. Technologies are therefore needed to enable this mission. The current alternatives are using nuclear propulsion, either with radioisotope or reactor power system or solar sailing. All these alternatives are currently being investigated. Other challenges exist as well such as designing a communication link

  15. 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.

  16. 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.

  17. Diagnostic applications of DNA probes.

    PubMed

    Pfaller, M A

    1991-02-01

    This review has described several of the most common molecular biologic techniques that are, or will be, employed in the diagnostic laboratory. The potential advantages of these DNA probe assays in the diagnosis of infectious diseases include: rapid detection and identification of infectious agents; the ability to screen selected specimens using batteries of probes; and the detection of nonviable or difficult-to-culture organisms. The potential disadvantages of DNA probe assays include: the use of isotopic detection methods for optimum sensitivity; limited diagnostic sensitivity of current assays; slow turna-round time for some assay formats; expense of current reagents; limited availability of many probes; lack of technical expertise in most diagnostic laboratories; and the requirement for antimicrobial susceptibility testing (requires culture). Given the above advantages and disadvantages, there are several key issues that must be considered before adopting DNA probe technology in the diagnostic laboratory; the cost of performing routine culture and identification versus the cost of screening with probes--both the number and type of specimens and the time savings that may be realized by eliminating routine cultures; the prevalence of the infectious agent--even the best DNA probe assay may not be useful or practical in a low-prevalence situation; the need for additional equipment and space; and the interpretation of false-positive and false-negative results--additional research is needed in this area. However, laboratories must consider these issues when using a test other than the current gold standard (i.e., culture). DNA probe technology is with us and expanding rapidly. The intelligent application of this new technology will require communication between laboratorians and clinicians and careful consideration of the many advantages and disadvantages discussed above.

  18. Histochemical staining using lectin probes.

    PubMed

    Akimoto, Yoshihiro; Kawakami, Hayato

    2014-01-01

    In histochemistry and cytochemistry, lectins are often used as probes for the localization of carbohydrates in cells and tissues. With lectins, cells and tissues can be identified as a particular type or a group in situ. Various lectins have been used for mapping of normal cells and tissues, pathological diagnosis such as malignant transformation, and identification of cell lineages during development. This chapter describes light and electron microscopic methods using lectin probes for determining carbohydrate localization in cells and tissues.

  19. 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

  20. Planetary Landers and Entry Probes

    NASA Astrophysics Data System (ADS)

    Ball, Andrew J.; Garry, James R. C.; Lorenz, Ralph D.; Kerzhanovich, Viktor V.

    2007-05-01

    Preface; Acknowledgements; Part I. Engineering Issues Specific to Entry Probes, Landers or Penetrators: 1. Mission goals and system engineering; 2. Accommodation, launch, cruise and arrival from orbit or interplanetary trajectory; 3. Entering atmospheres; 4. Descent through an atmosphere; 5. Descent to an airless body; 6. Planetary balloons, aircraft, submarines and cryobots; 7. Arrival at a surface; 8. Thermal control of landers and entry probes; 9. Power systems; 10. Communication and tracking of entry probes; 11. Radiation environment; 12. Surface activities: arms, drills, moles and mobility; 13. Structures; 14. Contamination of spacecraft and planets; Part II. Previous Atmosphere/Surface Vehicles and Their Payloads: 15. Destructive impact probes; 16. Atmospheric entry probes; 17. Pod landers; 18. Legged landers; 19. Payload delivery penetrators; 20. Small body surface missions; Part III. 'Case Studies': 21. Surveyor landers; 22. Galileo probe; 23. Huygens; 24. Mars Pathfinder and Sojourner; 25. Deep Space 2 Mars microprobes; 26. Rosetta lander Philae; 27. Mars exploration rovers: Spirit and Opportunity; Appendix: Some key parameters for bodies in the Solar System; List of acronyms; Bibliography; References; Index.

  1. Planetary Landers and Entry Probes

    NASA Astrophysics Data System (ADS)

    Ball, Andrew; Garry, James; Lorenz, Ralph; Kerzhanovich, Viktor

    2010-02-01

    Preface; Acknowledgements; Part I. Engineering Issues Specific to Entry Probes, Landers or Penetrators: 1. Mission goals and system engineering; 2. Accommodation, launch, cruise and arrival from orbit or interplanetary trajectory; 3. Entering atmospheres; 4. Descent through an atmosphere; 5. Descent to an airless body; 6. Planetary balloons, aircraft, submarines and cryobots; 7. Arrival at a surface; 8. Thermal control of landers and entry probes; 9. Power systems; 10. Communication and tracking of entry probes; 11. Radiation environment; 12. Surface activities: arms, drills, moles and mobility; 13. Structures; 14. Contamination of spacecraft and planets; Part II. Previous Atmosphere/Surface Vehicles and Their Payloads: 15. Destructive impact probes; 16. Atmospheric entry probes; 17. Pod landers; 18. Legged landers; 19. Payload delivery penetrators; 20. Small body surface missions; Part III. 'Case Studies': 21. Surveyor landers; 22. Galileo probe; 23. Huygens; 24. Mars Pathfinder and Sojourner; 25. Deep Space 2 Mars microprobes; 26. Rosetta lander Philae; 27. Mars exploration rovers: Spirit and Opportunity; Appendix: Some key parameters for bodies in the Solar System; List of acronyms; Bibliography; References; Index.

  2. Evaluation of an Electronic Periodontal Probe Versus a Manual Probe

    PubMed Central

    Trentzsch, Lars; Schönfelder, Antje; Schwarzenberger, Fabian; Jentsch, Holger

    2016-01-01

    Introduction Diagnosis of periodontal diseases requires reco-rding of clinical and periodontal variables. Possible measurement errors in recording the periodontal findings are dependent on the measurement method. Aim The purpose of the trial was to investigate an electronic, pressure-calibrated probe compared with a standard, manual measurement probe used to take periodontal variables. Materials and Methods The study included 25 subjects suffering from periodontal disease. Their findings were taken by two users on a randomized basis using a standard probe and an electronic, pressure calibrated probe, at an interval of 24 hours. The recorded clinical variables contained Pocket Depth (PD), Attachment Level (AL), Bleeding on Probing (BOP), the complete time needed to take the findings and the sensation of pain experienced by a Visual Analogue Scale (VAS). The data were statistically analyzed using the paired t-test. Results The measurement values (24 patients) for PD (p=0.03) and BOP (p=0.01) indicated a significant difference (paired t test, p>0.05), while there was no statistical difference for AL (p=0.064). A classification of PD into groups of 1-3mm, 4-6mm and ≥7mm showed that the manual method measured higher values than the electronic method (p=0.001). The measurement values did not reveal any significant differences (p>0.05) with respect to the total time needed to take findings and the measurement time for PD/AL. There was a significant difference (Wilcoxon-test, p<0.05) in VAS values (p=0.048) and in terms of the time needed to record the findings for BOP (p=0.004). Conclusion It can be assumed that the electronic probe should mainly be used in the supportive periodontal therapy. Present study showed that the use of a standard manual probe is essential to review conspicuous or unclear measurement values, or when treating deep pockets higher than 7mm. PMID:28050524

  3. 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.

  4. 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.

  5. 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.

  6. [Immune system and tumors].

    PubMed

    Terme, Magali; Tanchot, Corinne

    2017-02-01

    Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope.

  7. Epilepsy and brain tumors.

    PubMed

    Rudà, Roberta; Trevisan, Elisa; Soffietti, Riccardo

    2010-11-01

    To present an overview of the recent findings in pathophysiology and management of epileptic seizures in patients with brain tumors. Low-grade gliomas are the most epileptogenic brain tumors. Regarding pathophysiology, the role of peritumoral changes [hypoxia and acidosis, blood-brain barrier (BBB) disruption, increase or decrease of neurotransmitters and receptors] are of increasing importance. Tumor-associated epilepsy and tumor growth could have some common molecular pathways. Total/subtotal surgical resection (with or without epilepsy surgery) allows a seizure control in a high percentage of patients. Radiotherapy and chemotherapy as well have a role. New antiepileptic drugs are promising, both in terms of efficacy and tolerability. The resistance to antiepileptic drugs is still a major problem: new insights into pathogenesis are needed to develop strategies to manipulate the pharmakoresistance. Epileptic seizures in brain tumors have been definitely recognized as one of the major problems in patients with brain tumors, and need specific and multidisciplinary approaches.

  8. Uterine primitive neuroectodermal tumor.

    PubMed

    Aminimoghaddam, Soheila; Seifirad, Soroush; Abbasi Dezfouli, Golbahar; Abbasi, Neda; Zare Mehrjardi, Ali; Razavi, Seyed Mohsen; Mahmoudzadeh, Fatemeh

    2015-04-01

    Primitive neuroectodermal tumors are fairly rare in uterus. A case of uterine body primitive neuroectodermal tumor in a 32-year-old Iranian woman is presented. The patient was admitted with abdominal pain and fever and underwent emergency exploratory surgery with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection. Posterior wall of the uterus was necrotic and ruptured and a huge tumor disrupted the uterine body. The tumor was strongly positive for CD99, NSE, and chromogranin; No reaction was seen for CD10, CD45 and myogenin. To the best of our knowledge, this is the first report of an uterine body primitive neuroectodermal tumor and the second report of uterine primitive neuroectodermal tumor from Iran.

  9. [Simultaneous digestive tumors].

    PubMed

    Bourbon, L M

    2000-01-01

    Synchronous and metachronous gastrointestinal tumors are well know entities, describing malignant tumors placed in the same organ, at the time of initial diagnosis or during the follow-up control. I would like to present two cases of malignant tumors placed in different organs of the digestive tube, at the time of diagnosis, coining the name simultaneous for these entities, stating laboratory finding and signo-symptomatologic interpretation difficulties, and proposing endoscopic approach as a valid diagnostic method.

  10. Opening Windows into Tumors.

    PubMed

    Simberg, Dmitri

    2015-09-22

    Delivery of nanoparticles to tumors is limited by vascular permeability and intratumoral diffusion. In this issue of ACS Nano, Jiang et al. show that the manipulation of tumor physiology using antiangiogenic therapy can improve the tumor penetration of quantum dots with 20 and 40 nm hydrodynamic diameters. This Perspective describes the problems, challenges, and perspectives of using antiangiogenic therapy in combination with nanometer-sized drugs and contrast agents in preclinical and clinical studies.

  11. In vivo imaging of tumor vascular endothelial cells

    NASA Astrophysics Data System (ADS)

    Zhao, Dawen; Stafford, Jason H.; Zhou, Heling; Thorpe, Philip E.

    2013-02-01

    Phosphatidylserine (PS), normally restricted to the inner leaflet of the plasma membrane, becomes exposed on the outer surface of viable (non-apoptotic) endothelial cells in tumor blood vessels, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we optically imaged exposed PS on tumor vasculature in vivo using PGN635, a novel human monoclonal antibody that targets PS. PGN635 F(ab')2 was labeled with the near infrared (NIR) dye, IRDye 800CW. Human glioma U87 cells or breast cancer MDA-MB-231 cells were implanted subcutaneously or orthotopically into nude mice. When the tumors reached ~5 mm in diameter, 800CW- PGN635 was injected via a tail vein and in vivo dynamic NIR imaging was performed. For U87 gliomas, NIR imaging allowed clear detection of tumors as early as 4 h later, which improved over time to give a maximal tumor/normal ratio (TNR = 2.9 +/- 0.5) 24 h later. Similar results were observed for orthotopic MDA-MB-231 breast tumors. Localization of 800CW-PGN635 to tumors was antigen specific since 800CW-Aurexis, a control probe of irrelevant specificity, did not localize to the tumors, and pre-administration of unlabeled PGN635 blocked the uptake of 800CW-PGN635. Fluorescence microscopy confirmed that 800CW-PGN635 was binding to PS-positive tumor vascular endothelium. Our studies suggest that tumor vasculature can be successfully imaged in vivo to provide sensitive tumor detection.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Probe permeametry: An overview and bibliography

    SciTech Connect

    Hurst, A.; Goggin, D.

    1995-03-01

    Applications of probe permeameters in both laboratory and outcrop studies of permeability heterogeneity are common. We present an overview of the current status of probe permeameter data acquisition, analysis, and application. The multidisciplinary nature of probe permeameter studies has led to their publication in diverse scientific journals. We present a bibliography that includes literature covering both the technology and the application of probe permeametry.

  17. 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

  18. 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

  19. 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

  20. Canine mammary gland tumors.

    PubMed

    Sorenmo, Karin

    2003-05-01

    The National Consensus Group recommends that all women with tumors larger than 1 cm be offered chemotherapy regardless of tumor histology of lymph node status. This recommendation is to ensure that everyone at risk for failing, even though the risk may be low in women with relatively small tumors and favorable histology, has a choice and receives the benefit of adjuvant chemotherapy. This type of treatment recommendation may also be made in dogs based on recognized, well-accepted prognostic factors such as tumor size, stage, type, and histologic differentiation. Based on the limited clinical information available in veterinary medicine, the drugs that are effective in human breast cancer, such as cyclophosphamide, 5-fluorouracil, and doxorubicin, may also have a role in the treatment of malignant mammary gland tumors in dogs. Randomized prospective studies are needed, however, to evaluate the efficacy of chemotherapy in dogs with high-risk mammary gland tumors and to determine which drugs and protocols are the most efficacious. Until such studies are performed, the treatment of canine mammary gland tumors will be based on the individual oncologist's understanding of tumor biology, experience, interpretation of the available studies, and a little bit of gut-feeling. Table 2 is a proposal for treatment guidelines for malignant canine mammary gland tumors according to established prognostic factors, results from published veterinary studies, and current recommendations for breast cancer treatment in women.

  1. [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.

  2. CNS and spinal tumors.

    PubMed

    Furtado, Andre D; Panigrahy, Ashok; Fitz, Charles R

    2016-01-01

    Primary CNS tumors consist of a diverse group of neoplasms originating from various cell types in the CNS. Brain tumors are the most common solid malignancy in children under the age of 15 years and the second leading cause of cancer death after leukemia. The most common brain neoplasms in children differ consistently from those in older age groups. Pediatric brain tumors demonstrate distinct patterns of occurrence and biologic behavior according to sex, age, and race. This chapter highlights the imaging features of the most common tumors that affect the child's CNS (brain and spinal cord).

  3. 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.

  4. Magnetically engineered semiconductor quantum dots as multimodal imaging probes.

    PubMed

    Jing, Lihong; Ding, Ke; Kershaw, Stephen V; Kempson, Ivan M; Rogach, Andrey L; Gao, Mingyuan

    2014-10-08

    Light-emitting semiconductor quantum dots (QDs) combined with magnetic resonance imaging contrast agents within a single nanoparticle platform are considered to perform as multimodal imaging probes in biomedical research and related clinical applications. The principles of their rational design are outlined and contemporary synthetic strategies are reviewed (heterocrystalline growth; co-encapsulation or assembly of preformed QDs and magnetic nanoparticles; conjugation of magnetic chelates onto QDs; and doping of QDs with transition metal ions), identifying the strengths and weaknesses of different approaches. Some of the opportunities and benefits that arise through in vivo imaging using these dual-mode probes are highlighted where tumor location and delineation is demonstrated in both MRI and fluorescence modality. Work on the toxicological assessments of QD/magnetic nanoparticles is also reviewed, along with progress in reducing their toxicological side effects for eventual clinical use. The review concludes with an outlook for future biomedical imaging and the identification of key challenges in reaching clinical applications.

  5. Prototype of a single probe Compton camera for laparoscopic surgery

    NASA Astrophysics Data System (ADS)

    Koyama, A.; Nakamura, Y.; Shimazoe, K.; Takahashi, H.; Sakuma, I.

    2017-02-01

    Image-guided surgery (IGS) is performed using a real-time surgery navigation system with three-dimensional (3D) position tracking of surgical tools. IGS is fast becoming an important technology for high-precision laparoscopic surgeries, in which the field of view is limited. In particular, recent developments in intraoperative imaging using radioactive biomarkers may enable advanced IGS for supporting malignant tumor removal surgery. In this light, we develop a novel intraoperative probe with a Compton camera and a position tracking system for performing real-time radiation-guided surgery. A prototype probe consisting of Ce :Gd3 Al2 Ga3 O12 (GAGG) crystals and silicon photomultipliers was fabricated, and its reconstruction algorithm was optimized to enable real-time position tracking. The results demonstrated the visualization capability of the radiation source with ARM = ∼ 22.1 ° and the effectiveness of the proposed system.

  6. 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.

  7. Sentinel node in cancer diagnosis with surgical probes

    NASA Astrophysics Data System (ADS)

    Kazandjian, Anne; Prat, Vincent; Simon, Herve; Ricard, Marcel; Bede, Jessica

    1999-10-01

    A probe system has been designed for the accurate location of areas of increased radionuclide uptake. Different type of applications are possible i.e. when precise position or even identification of the radionuclide is needed, like in wound investigation. In this paper, we restrict ourself to a system incorporating two probes, for the identification of `hot' lymph nodes, close to the surface of the body. Axillary lymph node involvement is a major prognostic indicator and treatment planning factor in both melanoma and breast cancer. However, sentinel node localization is relatively difficult often due to close proximity of the primary tumor. The developed instrument has a very sensitive detector, with good spatial resolution, able to discriminate between primary and scattered radiations.

  8. Initial laboratory experience with a novel ultrasound probe for standard and single-port robotic kidney surgery: increasing console surgeon autonomy and minimizing instrument clashing.

    PubMed

    Yakoubi, Rachid; Autorino, Riccardo; Laydner, Humberto; Guillotreau, Julien; White, Michael A; Hillyer, Shahab; Spana, Gregory; Khanna, Rakesh; Isaac, Wahib; Haber, Georges-Pascal; Stein, Robert J; Kaouk, Jihad H

    2012-06-01

    The aim of this study was to evaluate a novel ultrasound probe specifically developed for robotic surgery by determining its efficiency in identifying renal tumors. The study was carried out using the Da Vinci™ surgical system in one female pig. Renal tumor targets were created by percutaneous injection of a tumor mimic mixture. Single-port and standard robotic partial nephrectomy were performed. Intraoperative ultrasound was performed using both standard laparoscopic probe and the new ProART™ Robotic probe. Probe maneuverability and ease of handling for tumor localization were recorded. The standard laparoscopic probe was guided by the assistant. Significant clashing with robotic arms was noted during the single-port procedure. The novel robotic probe was easily introduced through the assistant trocar, and held by the console surgeon using the robotic Prograsp™ with no registered clashing in the external operative field. The average time for grasping the new robotic probe was less than 10 s. Once inserted and grasped, no limitation was found in terms of instrument clashing during the single-port procedure. This novel ultrasound probe developed for robotic surgery was noted to be user-friendly when performing porcine standard and especially single-port robotic partial nephrectomy. Copyright © 2011 John Wiley & Sons, Ltd.

  9. Selective fluorescence probes for dipeptidyl peptidase activity-fibroblast activation protein and dipeptidyl peptidase IV.

    PubMed

    Lai, Koon Siew; Ho, Nan-Hui; Cheng, Jonathan D; Tung, Ching-Hsuan

    2007-01-01

    Development of suitable tools to assess enzyme activity directly from their complex cellular environment has a dramatic impact on understanding the functional roles of proteins as well as on the discovery of new drugs. In this study, a novel fluorescence-based chemosensor strategy for the direct readout of dipeptidase activities within intact living cells is described. Selective activity-based probes were designed to sense two important type II transmembrane serine proteases, fibroblast activation protein (FAP) and dipeptidyl peptidase IV (DPP-IV). These serine proteases have been implicated in diverse cellular activities, including blood coagulation, digestion, immune responses, wound healing, tumor growth, tumor invasion, and metastasis. Here, we validated that Ac-GPGP-2SBPO and GPGP-2SBPO probes are excellent reporters of both proteolytic activities. Furthermore, the novel probes can differentiate between FAP and DPP-IV proteolytic activities in cellular assay. Potentially, this assay platform is immediately useful for novel drug discovery.

  10. Selective Fluorescence Probes for Dipeptidyl Peptidase Activity - Fibroblast Activation Protein and Dipeptidyl Peptidase IV

    PubMed Central

    Lai, Koon Siew; Ho, Nan-Hui; Cheng, Jonathan D.; Tung, Ching-Hsuan

    2008-01-01

    Development of suitable tools to assess enzyme activity directly from their complex cellular environment has a dramatic impact on understanding the functional roles of proteins as well as on the discovery of new drugs. In this study, a novel fluorescence-based chemosensor strategy for the direct readout of dipeptidase activities within intact living cells is described. Selective activity-based probes were designed to sense two important type II transmembrane serine proteases, Fibroblast activation protein (FAP) and Dipeptidyl peptidase IV (DPP-IV). These serine proteases have been implicated in diverse cellular activities, including blood coagulation, digestion, immune responses, wound healing, tumor growth, tumor invasion and metastasis. We here validated that Ac-GPGP-2SBPO and GPGP-2SBPO probes are excellent reporters of both proteolytic activities. Furthermore, the novel probes can differentiate between FAP and DPP-IV proteolytic activities in cellular assay. Potentially, this assay platform is immediately useful for novel drug discovery. PMID:17489551

  11. 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.

  12. 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

  13. 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.

  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. Molecular Probes for Imaging the Sigma-2 Receptor: In Vitro and In Vivo Imaging Studies.

    PubMed

    Zeng, Chenbo; McDonald, Elizabeth S; Mach, Robert H

    2017-02-08

    The sigma-2 (σ2) receptor has been validated as a biomarker of the proliferative status of solid tumors. Therefore, radiotracers having a high affinity and high selectivity for σ2 receptors have the potential to assess the proliferative status of human tumors using noninvasive imaging techniques such as Positron Emission Tomography (PET). Since the σ2 receptor has not been cloned, the current knowledge of this receptor has relied on receptor binding studies with the radiolabeled probes and investigation of the effects of the σ2 receptor ligands on tumor cells. The development of the σ2 selective fluorescent probes has proven to be useful for studying subcellular localization and biological functions of the σ2 receptor, for revealing pharmacological properties of the σ2 receptor ligands, and for imaging cell proliferation. Preliminary clinical imaging studies with [(18)F]ISO-1, a σ2 receptor probe, have shown promising results in cancer patients. However, the full utility of imaging the σ2 receptor status of solid tumors in the diagnosis and prediction of cancer therapeutic response will rely on elucidation of the functional role of this protein in normal and tumor cell biology.

  16. Multimodal nonlinear endo-microscopy probe design for high resolution, label-free intraoperative imaging

    PubMed Central

    Chen, Xu; Xu, Xiaoyun; McCormick, Daniel T.; Wong, Kelvin; Wong, Stephen T.C.

    2015-01-01

    We present a portable, multimodal, nonlinear endo-microscopy probe designed for intraoperative oncological imaging. Application of a four-wave mixing noise suppression scheme using dual wavelength wave plates (DWW) and a polarization-maintaining fiber improves tissue signal collection efficiency, allowing for miniaturization. The probe, with a small 14 mm transversal diameter, includes a customized miniaturized two-axis MEMS (micro-electromechanical system) raster scanning mirror and micro-optics with an illumination laser delivered by a polarization-maintaining fiber. The probe can potentially be integrated into the arms of a surgical robot, such as da Vinci robotic surgery system, due to its minimal cross sectional area. It has the ability to incorporate multiple imaging modalities including CARS (coherent anti-Stokes Raman scattering), SHG (second harmonic generation), and TPEF (two-photon excited fluorescence) in order to allow the surgeon to locate tumor cells within the context of normal stromal tissue. The resolution of the endo-microscope is experimentally determined to be 0.78 µm, a high level of accuracy for such a compact probe setup. The expected resolution of the as-built multimodal, nonlinear, endo-microscopy probe is 1 µm based on the calculation tolerance allocation using Monte-Carlo simulation. The reported probe is intended for use in laparoscopic or radical prostatectomy, including detection of tumor margins and avoidance of nerve impairment during surgery. PMID:26203361

  17. Nanofabrication using near-field optical probes

    PubMed Central

    McLeod, Euan; Ozcan, Aydogan

    2012-01-01

    Nanofabrication using near-field optical probes is an established technique for rapid prototyping and automated maskless fabrication of nanostructured devices. In this review, we present the primary types of near-field probes and their physical processing mechanisms. Highlights of recent developments include improved resolution by optimizing the probe shape, incorporation of surface plasmonics in probe design, broader use in biological and magnetic storage applications, and increased throughput using probe arrays as well as high speed writing and patterning. PMID:22713756

  18. 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

  19. Using Intraoperative Ultrasonography for Spinal Cord Tumor Surgery.

    PubMed

    Ivanov, Marcel; Budu, Alexandru; Sims-Williams, Hugh; Poeata, Ion

    2017-01-01

    Our aim was to evaluate the usefulness of modern intraoperative ultrasonography (iUS) in the resection of a wide variety of spinal intradural pathologic entities. We evaluated patients with spinal cord disease treated between January 2006 and September 2015. Intraoperative standard B-mode images were acquired using a 3.5-MHz to 12-MHz ultrasonographic probes (linear and curvilinear) on various ultrasound machines. The benefits and disadvantages of iUS were assessed for each case. A total number of 158 intradural spinal lesions were operated on using iUS. Of these, 107 lesions (68%) were intradural extramedullary and 51 (32%) were intramedullary. All lesions were clearly visible using the ultrasound probe. The high-frequency linear probes (10-12 MHz) provided a better image quality compared with lower-frequency probes. Color and power-angiography modes were helpful in assessing the vascularization of the tumors and location of the major vessels in the vascular lesions. We document how iUS was used to facilitate safe and efficient spinal tumor resection at each stage of the operation. iUS was beneficial in confirmation of tumor location and extension, planning myelotomy, and estimation of degree of resection of the intramedullary tumors. It was particularly helpful in guiding the approach in redo surgeries for recurrent spinal cord tumors. iUS has a fast learning curve and offers additional intraoperative information that can help improve surgical accuracy and therefore may reduce procedure-related morbidity. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Spaser as a biological probe

    NASA Astrophysics Data System (ADS)

    Galanzha, Ekaterina I.; Weingold, Robert; Nedosekin, Dmitry A.; Sarimollaoglu, Mustafa; Nolan, Jacqueline; Harrington, Walter; Kuchyanov, Alexander S.; Parkhomenko, Roman G.; Watanabe, Fumiya; Nima, Zeid; Biris, Alexandru S.; Plekhanov, Alexander I.; Stockman, Mark I.; Zharov, Vladimir P.

    2017-06-01

    Understanding cell biology greatly benefits from the development of advanced diagnostic probes. Here we introduce a 22-nm spaser (plasmonic nanolaser) with the ability to serve as a super-bright, water-soluble, biocompatible probe capable of generating stimulated emission directly inside living cells and animal tissues. We have demonstrated a lasing regime associated with the formation of a dynamic vapour nanobubble around the spaser that leads to giant spasing with emission intensity and spectral width >100 times brighter and 30-fold narrower, respectively, than for quantum dots. The absorption losses in the spaser enhance its multifunctionality, allowing for nanobubble-amplified photothermal and photoacoustic imaging and therapy. Furthermore, the silica spaser surface has been covalently functionalized with folic acid for molecular targeting of cancer cells. All these properties make a nanobubble spaser a promising multimodal, super-contrast, ultrafast cellular probe with a single-pulse nanosecond excitation for a variety of in vitro and in vivo biomedical applications.

  1. 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.

  2. Recognition of Probe Ptolemaic Graphs

    NASA Astrophysics Data System (ADS)

    Chang, Maw-Shang; Hung, Ling-Ju

    Let G denote a graph class. An undirected graph G is called a probe G graph if one can make G a graph in G by adding edges between vertices in some independent set of G. By definition graph class G is a subclass of probe G graphs. Ptolemaic graphs are chordal and induced gem free. They form a subclass of both chordal graphs and distance-hereditary graphs. Many problems NP-hard on chordal graphs can be solved in polynomial time on ptolemaic graphs. We proposed an O(nm)-time algorithm to recognize probe ptolemaic graphs where n and m are the numbers of vertices and edges of the input graph respectively.

  3. 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.

  4. Outer Planets/Solar Probe Project: Solar Probe

    NASA Technical Reports Server (NTRS)

    Tsurutani, B. T.

    2000-01-01

    Solar Probe, the first mission to the Sun and the third of three missions in NASA's Outer Solar System/Solar Probe Program, is a voyage of exploration, discovery, and comprehension. This near-Sun flyby will provide in situ measurements in the solar corona and high-resolution pictures and magnetograms of the photosphere and polar atmosphere. These measurements are also needed as "ground truth" for interpreting the many measurements of the Sun and solar activity that have been made from a distance of 1 AU. Solar Probe is scheduled for launch in February 2007. It will arrive at the Sun along a polar trajectory perpendicular to the Sun-Earth line with a perihelion of 4 solar radii (R(sub s)) from the Sun's center. Two perihelion passages will occur, the first in 2010 (near solar sunspot maximum) and the second in 2015 (near solar minimum) ensuring measurement of both coronal hole and streamer-related solar wind properties. To reach the Sun, probe must first fly to Jupiter and use a gravity assist to lose its angular momentum about the Sun. The imaging and in situ miniaturized instruments will provide the first 3-dimensional view of the corona, high spatial- and temporal-resolutions of the magnetic fields, and helioseismic measurements of the polar regions, as well as sporadic high-spatial-resolution local sampling of plasmas and fields at all latitudes.

  5. Brain and Spinal Tumors

    MedlinePlus

    ... National Brain Tumor Society 55Chapel Street Suite 200 Newton MA Newton, MA 02458 questions@braintumor.org http://www.braintumor. ... National Brain Tumor Society 55Chapel Street Suite 200 Newton MA Newton, MA 02458 questions@braintumor.org http:// ...

  6. Vanishing tumor in pregnancy

    PubMed Central

    Vimal, M. V.; Budyal, Sweta; Kasliwal, Rajeev; Jagtap, Varsha S.; Lila, Anurag R.; Bandgar, Tushar; Menon, Padmavathy; Shah, Nalini S.

    2012-01-01

    A patient with microprolactinoma, who had two successful pregnancies, is described for management issues. First pregnancy was uneventful. During the second pregnancy, the tumor enlarged to macroprolactinoma with headache and blurring of vision which was managed successfully with bromocriptine. Post delivery, complete disappearance of the tumor was documented. PMID:23226664

  7. 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.

  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. In vivo Magnetic Resonance Imaging of Tumor Protease Activity

    PubMed Central

    Haris, Mohammad; Singh, Anup; Mohammed, Imran; Ittyerah, Ranjit; Nath, Kavindra; Nanga, Ravi Prakash Reddy; Debrosse, Catherine; Kogan, Feliks; Cai, Kejia; Poptani, Harish; Reddy, Damodar; Hariharan, Hari; Reddy, Ravinder

    2014-01-01

    Increased expression of cathepsins has diagnostic as well as prognostic value in several types of cancer. Here, we demonstrate a novel magnetic resonance imaging (MRI) method, which uses poly-L-glutamate (PLG) as an MRI probe to map cathepsin expression in vivo, in a rat brain tumor model. This noninvasive, high-resolution and non-radioactive method exploits the differences in the CEST signals of PLG in the native form and cathepsin mediated cleaved form. The method was validated in phantoms with known physiological concentrations, in tumor cells and in an animal model of brain tumor along with immunohistochemical analysis. Potential applications in tumor diagnosis and evaluation of therapeutic response are outlined. PMID:25124082

  10. Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors

    PubMed Central

    Metz, David C.

    2008-01-01

    Pancreatic endocrine tumors (PETs) have long fascinated clinicians and investigators despite their relative rarity. Their clinical presentation varies depending upon whether the tumor is functional or not and also according to the specific hormonal syndrome produced. Tumors may be sporadic or inherited but little is known about their molecular pathology, especially the sporadic forms. Chromogranin A appears to be the most useful serum marker for diagnosis, staging and monitoring. Initially, therapy should be directed at the hormonal syndrome as this has the major initial impact on the patient's health. Most PETs are relatively indolent but ultimately malignant, except for insulinomas which are predominantly benign. Surgery is the only modality that offers the possibility of cure although it is generally noncurative in patients with Zollinger-Ellison syndrome or nonfunctional PETs with MEN1. Preoperative staging of disease extent is necessary to determine the likelihood of complete resection though debulking surgery is often felt to be useful in unresectable patients. Once metastatic, biotherapy is usually the first modality employed because it is generally well tolerated. Systemic or regional therapies are generally reserved until symptoms occur or tumor growth is rapid. Recently a number of newer agents, as well as receptor-directed radiotherapy, are being evalulated for patients with advanced disease. This review addresses a number of recent advances regarding the molecular pathology, diagnosis, localization and management of PETs including discussion of peptide receptor radionuclide therapy and other novel antitumor approaches. We conclude with a discussion of future directions and unsettled problems in the field. PMID:18703061

  11. Merkel cell tumor.

    PubMed

    Kitazawa, M; Watanabe, H; Kobayashi, H; Ohnishi, Y; Shitara, A; Nitto, H

    1987-06-01

    A Merkel cell tumor appeared on the left cheek of an 83-year-old female was reported. The tumor was located mainly in the dermis and infiltrated to the subcutaneous adipose tissue with an involvement of the blood vessels and lymphatics at the periphery. Electron-microscopically, few of the dense-cored granules and the single globular aggregates of intermediate filaments at the nuclear indentations were observed. Electron-microscopic uranaffin reaction proved positive reaction on the dense-cored granules. Half of the cytoplasmic border was smooth, while the rest had short projections. Desmosomes or junctional complexes were not detected among the tumor cells. Immunohistochemically, the cytoplasm of tumor cell showed positive reaction to both neuron-specific enolase (NSE) and keratin. The single globular positive spots of the latter were localized in accordance with the aggregates of intermediate filaments. These findings suggested a neurogenic origin with double differentiation, epithelial and neuroendocrine, of the Merkel cell tumor.

  12. 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.

  13. Acetate Dependence of Tumors

    PubMed Central

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

    2014-01-01

    SUMMARY Acetyl-CoA represents a central node of carbon metabolism that plays a key role in bioenergetics, cell proliferation and the regulation of gene expression. How highly glycolytic or hypoxic tumors are able to produce sufficient quantities of this metabolite to support cell growth and survival under nutrient-limiting conditions remains poorly understood. 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. PMID:25525877

  14. Neonatal Brain Tumors: A Review

    PubMed Central

    Bodeliwala, Shaam; Kumar, Vikas; Singh, Daljit

    2017-01-01

    Brain tumors in neonatal age group is uncommon comparing with older children and adults. In older children brain tumors are commonly infratentorial, where as in neonates, they are supratentorial. Though extracranial tumors are commoner in neonates, brain tumors cause 5-20% deaths approximately. We are presenting a review on brain tumors in neonates. PMID:28770127

  15. Construction of specific magnetic resonance imaging/optical dual-modality molecular probe used for imaging angiogenesis of gastric cancer.

    PubMed

    Yan, Xuejie; Song, Xiaoyan; Wang, Zhenbo

    2017-05-01

    The purpose of the study was to construct specific magnetic resonance imaging (MRI)/optical dual-modality molecular probe. Tumor-bearing animal models were established. MRI/optical dual-modality molecular probe was construed by coupling polyethylene glycol (PEG)-modified nano-Fe3O4 with specific targeted cyclopeptide GX1 and near-infrared fluorescent dyes Cy5.5. MRI/optical imaging effects of the probe were observed and the feasibility of in vivo double-modality imaging was discussed. It was found that, the double-modality probe was of high stability; tumor signal of the experimental group tended to be weak after injection of the probe, but rose to a level which was close to the previous level after 18 h (p > 0.05). We successively completed the construction of an ideal MRI/optical dual-modality molecular probe. MRI/optical dual-modality molecular probe which can selectively gather in gastric cancer is expected to be a novel probe used for diagnosing gastric cancer in the early stage.

  16. Real-time noninvasive optoacoustic monitoring of nanoparticle-mediated photothermal therapy of tumors

    NASA Astrophysics Data System (ADS)

    Esenaliev, R. O.; Petrov, Y. Y.; Cicenaite, I.; Chumakova, O. V.; Petrova, I. Y.; Patrikeev, I.; Liopo, A.

    2007-02-01

    We proposed and have been developing real-time, noninvasive monitoring of blood oxygenation, total hemoglobin concentration, and thermotherapy including hyperthermia, coagulation, and cryotherapy. In this paper we propose to use the optoacoustic technique for monitoring of nanoparticle-mediated photothermal therapy (NPT) of tumors. NPT is based on heating exogenous strongly-absorbing nanoparticles selectively delivered in tumors. Real-time monitoring of NPT is necessary for precise tumor therapy with minimal damage to normal tissues. In this study we injected PEGylated and non-PEGylated carbon nanoparticles in nude mice bearing human tumors (5-15 mm) and irradiated the tumors for 10 minutes with nanosecond Nd:YAG laser pulses which produced both thermal damage to the tumors and optoacoustic signals for monitoring NPT in real time. Irradiation of tumors was performed during or after (3 or 24 hours) nanoparticle injection. Amplitude and temporal parameters of optoacoustic signals (measured with a custom-made wide-band optoacoustic probe) correlated well with nanoparticle injection, temperature rise in tumors, and tumor coagulation. Substantial thermal damage in large areas of the tumors was produced when optimal irradiation parameters were used. Monte Carlo modeling of light distribution in tumors and optoacoustic theory were applied to study kinetics of nanoparticle concentration in the tumors. Our results demonstrated that the optoacoustic technique can be used for real-time monitoring of NTP and provide precise tumor therapy with minimal damage to normal tissues.

  17. Saturn Science from Entry Probes

    NASA Astrophysics Data System (ADS)

    Atkinson, David H.; Coustenis, Athena; Lunine, Jonathan; Simon-Miller, Amy; Atreya, Sushil; Brinckerhoff, William; Colaprete, Anthony; Guillot, Tristan; Mahaffy, Paul; Reh, Kim; Spilker, Linda; Spilker, Tom; Webster, Chris

    2013-04-01

    Data from atmospheric entry probe missions at the giant planets could uniquely discriminate between competing theories of solar system formation and the origin and evolution of the giant planets and their atmospheres, providing for valuable comparative studies of giant planets as well as providing a laboratory for studying the atmospheric chemistries, dynamics, and interiors of all the planets including Earth. The giant planets also represent a valuable link to extrasolar planetary systems. For these reasons, a Saturn Probe mission with a shallow probe is ranked by the recent U.S. Planetary Science Decadal Survey as a high priority for a New Frontiers class mission. Atmospheric constituents needed to constrain theories of solar system formation and the origin and evolution of the giant planets could be accessed and sampled by shallow entry probes. Many important constituents are either spectrally inactive or are beneath an atmospheric overburden that is optically thick at useful wavelengths and are therefore not remotely accessible by flyby or orbiting spacecraft. A small, scientifically focused shallow entry probe mission could make critical abundance measurements of key constituents, and could measure profiles of atmospheric structure and dynamics at a vertical resolution that is significantly higher than could be achieved by remote sensing techniques. The Galileo mission began the detailed study of the solar system's two gas giants by dropping an entry probe into the atmosphere of Jupiter and deploying an orbiter around Jupiter. In 2016-2017 the Juno mission will make measurements of Jupiter's deep oxygen abundance, and gravitational and magnetic fields. In the same epoch, the Cassini orbiter is planned to pursue a set of Juno-like orbits to make comparable gravitational and magnetic field measurements of Saturn. A Saturn atmospheric entry probe would complete the quartet of missions needed for a comparative study of the two gas giants, leading to improved

  18. Can Wilms Tumor Be Found Early?

    MedlinePlus

    ... Wilms Tumor Early Detection, Diagnosis, and Staging Can Wilms Tumor Be Found Early? Wilms tumors are usually found ... Your Child’s Doctor About Wilms Tumor? More In Wilms Tumor About Wilms Tumor Causes, Risk Factors, and Prevention ...

  19. What Happens After Treatment for Wilms Tumor?

    MedlinePlus

    ... Tumor After Treatment What Happens After Treatment for Wilms Tumor? During and after treatment for Wilms tumors, the ... Wilms Tumor Survivors and Their Families More In Wilms Tumor About Wilms Tumor Causes, Risk Factors, and Prevention ...

  20. In vivo Detection of Phospholipase C by Enzyme-Activated Near-infrared Probes

    PubMed Central

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

    2011-01-01

    In this paper 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. Due to 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 IC50 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 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. PMID:22034913