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  1. Is it beneficial to selectively boost high-risk tumor subvolumes? A comparison of selectively boosting high-risk tumor subvolumes versus homogeneous dose escalation of the entire tumor based on equivalent EUD plans

    International Nuclear Information System (INIS)

    Kim, Yusung; To me, Wolfgang A.

    2008-01-01

    Purpose. To quantify and compare expected local tumor control and expected normal tissue toxicities between selective boosting IMRT and homogeneous dose escalation IMRT for the case of prostate cancer. Methods. Four different selective boosting scenarios and three different high-risk tumor subvolume geometries were designed to compare selective boosting and homogeneous dose escalation IMRT plans delivering the same equivalent uniform dose (EUD) to the entire PTV. For each scenario, differences in tumor control probability between both boosting strategies were calculated for the high-risk tumor subvolume and remaining low-risk PTV, and were visualized using voxel based iso-TCP maps. Differences in expected rectal and bladder complications were quantified using radiobiological indices (generalized EUD (gEUD) and normal tissue complication probability (NTCP)) as well as %-volumes. Results. For all investigated scenarios and high-risk tumor subvolume geometries, selective boosting IMRT improves expected TCP compared to homogeneous dose escalation IMRT, especially when lack of control of the high-risk tumor subvolume could be the cause for tumor recurrence. Employing, selective boosting IMRT significant increases in expected TCP can be achieved for the high-risk tumor subvolumes. The three conventional selective boosting IMRT strategies, employing physical dose objectives, did not show significant improvement in rectal and bladder sparing as compared to their counterpart homogeneous dose escalation plans. However, risk-adaptive optimization, utilizing radiobiological objective functions, resulted in reduction in NTCP for the rectum when compared to its corresponding homogeneous dose escalation plan. Conclusions. Selective boosting is a more effective method than homogeneous dose escalation for achieving optimal treatment outcomes. Furthermore, risk-adaptive optimization increases the therapeutic ratio as compared to conventional selective boosting IMRT

  2. A Patient-Matched Entire First Metacarpal Prosthesis in Treatment of Giant Cell Tumor of Bone

    Directory of Open Access Journals (Sweden)

    Thipachart Punyaratabandhu

    2017-01-01

    Full Text Available Giant cell tumor of the bones occurring in the first metacarpals frequently requires entire metacarpal resection due to the aggressive nature and high rate of recurrence. Bone reconstruction can be performed with autogenous bone grafts. Here we describe a new technique of reconstruction using a patient-matched three-dimensional printed titanium first metacarpal prosthesis. This prosthesis has a special design for ligament reconstruction in the proximal and distal portions. Good hand function and aesthetic appearance were maintained at a 24-month follow-up visit. This reconstructive technique can avoid donor-site complications and spare the autogenous bone grafts for revision options.

  3. Satellite altimetry based rating curves throughout the entire Amazon basin

    Science.gov (United States)

    Paris, A.; Calmant, S.; Paiva, R. C.; Collischonn, W.; Silva, J. S.; Bonnet, M.; Seyler, F.

    2013-05-01

    The Amazonian basin is the largest hydrological basin all over the world. In the recent past years, the basin has experienced an unusual succession of extreme draughts and floods, which origin is still a matter of debate. Yet, the amount of data available is poor, both over time and space scales, due to factor like basin's size, access difficulty and so on. One of the major locks is to get discharge series distributed over the entire basin. Satellite altimetry can be used to improve our knowledge of the hydrological stream flow conditions in the basin, through rating curves. Rating curves are mathematical relationships between stage and discharge at a given place. The common way to determine the parameters of the relationship is to compute the non-linear regression between the discharge and stage series. In this study, the discharge data was obtained by simulation through the entire basin using the MGB-IPH model with TRMM Merge input rainfall data and assimilation of gage data, run from 1998 to 2010. The stage dataset is made of ~800 altimetry series at ENVISAT and JASON-2 virtual stations. Altimetry series span between 2002 and 2010. In the present work we present the benefits of using stochastic methods instead of probabilistic ones to determine a dataset of rating curve parameters which are consistent throughout the entire Amazon basin. The rating curve parameters have been computed using a parameter optimization technique based on Markov Chain Monte Carlo sampler and Bayesian inference scheme. This technique provides an estimate of the best parameters for the rating curve, but also their posterior probability distribution, allowing the determination of a credibility interval for the rating curve. Also is included in the rating curve determination the error over discharges estimates from the MGB-IPH model. These MGB-IPH errors come from either errors in the discharge derived from the gage readings or errors in the satellite rainfall estimates. The present

  4. DWI-associated entire-tumor histogram analysis for the differentiation of low-grade prostate cancer from intermediate-high-grade prostate cancer.

    Science.gov (United States)

    Wu, Chen-Jiang; Wang, Qing; Li, Hai; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin; Zhang, Yu-Dong

    2015-10-01

    To investigate diagnostic efficiency of DWI using entire-tumor histogram analysis in differentiating the low-grade (LG) prostate cancer (PCa) from intermediate-high-grade (HG) PCa in comparison with conventional ROI-based measurement. DW images (b of 0-1400 s/mm(2)) from 126 pathology-confirmed PCa (diameter >0.5 cm) in 110 patients were retrospectively collected and processed by mono-exponential model. The measurement of tumor apparent diffusion coefficients (ADCs) was performed with using histogram-based and ROI-based approach, respectively. The diagnostic ability of ADCs from two methods for differentiating LG-PCa (Gleason score, GS ≤ 6) from HG-PCa (GS > 6) was determined by ROC regression, and compared by McNemar's test. There were 49 LG-tumor and 77 HG-tumor at pathologic findings. Histogram-based ADCs (mean, median, 10th and 90th) and ROI-based ADCs (mean) showed dominant relationships with ordinal GS of Pca (ρ = -0.225 to -0.406, p Histogram 10th ADCs had dominantly high Az (0.738), Youden index (0.415), and positive likelihood ratio (LR+, 2.45) in stratifying tumor GS against mean, median and 90th ADCs, and ROI-based ADCs. Histogram mean, median, and 10th ADCs showed higher specificity (65.3%-74.1% vs. 44.9%, p histogram analysis had higher specificity, Az, Youden index, and LR+ for differentiation of PCa Gleason grade than ROI-based approach.

  5. Extensive tumor thrombus of hepatocellular carcinoma in the entire portal venous system detected on fluorodeoxyglucose positron emission tomography computed tomography

    International Nuclear Information System (INIS)

    Agrawal, Archi; Purandare, Nilendu; Shah, Sneha; Puranik, Ameya; Rangarajan, Venkatesh

    2013-01-01

    Detection of thrombus is usually an incidental finding on fluorodeoxyglucose positron emission tomography/computed tomography studies. Nevertheless this is an important finding in terms of disease prognostication and in planning the treatment strategy. We herein report a case of a 50-years-old male, a diagnosed case of hepatocellular carcinoma with extensive hypermetabolic thrombus involving the entire portal venous system. (author)

  6. Skull base tumors

    International Nuclear Information System (INIS)

    Kikinis, R.; Matsumae, M.; Jolesz, F.A.; Black, P.M.; Cline, H.E.; Lorenson, W.E.

    1991-01-01

    This paper reports on an image processing procedure for the planning of surgery of skull base tumors that can extract bone, vessels, tumor, and brain parenchyma and that permits resolution of cranial nerves. Three-dimensional (3D) reconstructions were generated from double-echo long TR interleaved conventional spin-echo and fast-spin-echo MR imaging data. Sixteen cases have been analyzed preoperatively. Image processing consisted of a multistep procedure combining a supervised multivariate analysis with neighborhood operations such as connectivity and erosion/dilation. 3D renderings of anatomic structures of interest were then generated. Cases were evaluated preoperatively and manipulated interactively with the computer-generated images by a team consisting of neuroradiologists, neurosurgeons, and craniofacial surgeons. The preparation of 3D reconstructions required only a few hours and was performed mostly by a research assistant. The preoperative analysis of the 3D reconstructions was found to be a valuable tool, providing information complementing the surgeon's understanding of a case as derived from conventional imaging. The interactive manipulation of data proved to be a powerful way to evaluate alternative surgical approaches

  7. Skull base tumor model.

    Science.gov (United States)

    Gragnaniello, Cristian; Nader, Remi; van Doormaal, Tristan; Kamel, Mahmoud; Voormolen, Eduard H J; Lasio, Giovanni; Aboud, Emad; Regli, Luca; Tulleken, Cornelius A F; Al-Mefty, Ossama

    2010-11-01

    Resident duty-hours restrictions have now been instituted in many countries worldwide. Shortened training times and increased public scrutiny of surgical competency have led to a move away from the traditional apprenticeship model of training. The development of educational models for brain anatomy is a fascinating innovation allowing neurosurgeons to train without the need to practice on real patients and it may be a solution to achieve competency within a shortened training period. The authors describe the use of Stratathane resin ST-504 polymer (SRSP), which is inserted at different intracranial locations to closely mimic meningiomas and other pathological entities of the skull base, in a cadaveric model, for use in neurosurgical training. Silicone-injected and pressurized cadaveric heads were used for studying the SRSP model. The SRSP presents unique intrinsic metamorphic characteristics: liquid at first, it expands and foams when injected into the desired area of the brain, forming a solid tumorlike structure. The authors injected SRSP via different passages that did not influence routes used for the surgical approach for resection of the simulated lesion. For example, SRSP injection routes included endonasal transsphenoidal or transoral approaches if lesions were to be removed through standard skull base approach, or, alternatively, SRSP was injected via a cranial approach if the removal was planned to be via the transsphenoidal or transoral route. The model was set in place in 3 countries (US, Italy, and The Netherlands), and a pool of 13 physicians from 4 different institutions (all surgeons and surgeons in training) participated in evaluating it and provided feedback. All 13 evaluating physicians had overall positive impressions of the model. The overall score on 9 components evaluated--including comparison between the tumor model and real tumor cases, perioperative requirements, general impression, and applicability--was 88% (100% being the best possible

  8. Entirely Carbohydrate-Based Vaccines: An Emerging Field for Specific and Selective Immune Responses

    Directory of Open Access Journals (Sweden)

    Sharmeen Nishat

    2016-05-01

    Full Text Available Carbohydrates are regarded as promising targets for vaccine development against infectious disease because cell surface glycans on many infectious agents are attributed to playing an important role in pathogenesis. In addition, oncogenic transformation of normal cells, in many cases, is associated with aberrant glycosylation of the cell surface glycan generating tumor associated carbohydrate antigens (TACAs. Technological advances in glycobiology have added a new dimension to immunotherapy when considering carbohydrates as key targets in developing safe and effective vaccines to combat cancer, bacterial infections, viral infections, etc. Many consider effective vaccines induce T-cell dependent immunity with satisfactory levels of immunological memory that preclude recurrence. Unfortunately, carbohydrates alone are poorly immunogenic as they do not bind strongly to the MHCII complex and thus fail to elicit T-cell immunity. To increase immunogenicity, carbohydrates have been conjugated to carrier proteins, which sometimes can impede carbohydrate specific immunity as peptide-based immune responses can negate antibodies directed at the targeted carbohydrate antigens. To overcome many challenges in using carbohydrate-based vaccine design and development approaches targeting cancer and other diseases, zwitterionic polysaccharides (ZPSs, isolated from the capsule of commensal anaerobic bacteria, will be discussed as promising carriers of carbohydrate antigens to achieve desired immunological responses.

  9. Basic study of entire whole-body PET scanners based on the OpenPET geometry

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Eiji, E-mail: rush@nirs.go.j [National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Yamaya, Taiga; Nishikido, Fumihiko; Inadama, Naoko; Murayama, Hideo [National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan)

    2010-09-21

    A conventional PET scanner has a 15-25 cm axial field-of-view (FOV) and images a whole body using about six bed positions. An OpenPET geometry can extend the axial FOV with a limited number of detectors. The entire whole-body PET scanner must be able to process a large amount of data effectively. In this work, we study feasibility of the fully 3D entire whole-body PET scanner using the GATE simulation. The OpenPET has 12 block detector rings with the ring diameter of 840 mm and each block detector ring consists of 48 depth-of-interaction (DOI) detectors. The OpenPET has the axial length of 895.95 mm with five parts of 58.95 mm open gaps. The OpenPET has higher single data loss than a conventional PET scanner at grouping circuits. NECR of the OpenPET decreases by single data loss. But single data loss is mitigated by separating the axially arranged detector into two parts. Also, multiple coincidences are found to be important for the entire whole-body PET scanner. The entire whole-body PET scanner with the OpenPET geometry promises to provide a large axial FOV with the open space and to have sufficient performance values. But single data loss at the grouping circuits and multiple coincidences are limited to the peak noise equivalent count rate (NECR) for the entire whole-body PET scanner.

  10. A Game-Based Approach to an Entire Physical Chemistry Course

    Science.gov (United States)

    Daubenfeld, Thorsten; Zenker, Dietmar

    2015-01-01

    We designed, implemented, and evaluated a game-based learning approach to increase student motivation and achievement for an undergraduate physical chemistry course. By focusing only on the most important game aspects, the implementation was realized with a production ratio of 1:8 (study load in hours divided by production effort in hours).…

  11. Geometrical tuning art for entirely subwavelength grating waveguide based integrated photonics circuits.

    Science.gov (United States)

    Wang, Zheng; Xu, Xiaochuan; Fan, Donglei; Wang, Yaguo; Subbaraman, Harish; Chen, Ray T

    2016-05-05

    Subwavelength grating (SWG) waveguide is an intriguing alternative to conventional optical waveguides due to the extra degree of freedom it offers in tuning a few important waveguide properties, such as dispersion and refractive index. Devices based on SWG waveguides have demonstrated impressive performances compared to conventional waveguides. However, the high loss of SWG waveguide bends jeopardizes their applications in integrated photonic circuits. In this work, we propose a geometrical tuning art, which realizes a pre-distorted refractive index profile in SWG waveguide bends. The pre-distorted refractive index profile can effectively reduce the mode mismatch and radiation loss simultaneously, thus significantly reduce the bend loss. This geometry tuning art has been numerically optimized and experimentally demonstrated in present study. Through such tuning, the average insertion loss of a 5 μm SWG waveguide bend is reduced drastically from 5.43 dB to 1.10 dB per 90° bend for quasi-TE polarization. In the future, the proposed scheme will be utilized to enhance performance of a wide range of SWG waveguide based photonics devices.

  12. No damage to bulk storage but entire customer bases wiped out in storm

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper reports that interviews with key LP-gas industry spokesmen in hurricane-ravaged South Florida following Andrew's terrifying visit presented a picture of unimaginable destruction and nearly immeasurable losses of property but miraculously, not a single significant incident involving leaks or the loss of bulk storage. In the worst reports of damage to propane company facilities, Homestead Gas loss at least one building and the Suburban/Petrolane office building in Homestead no longer exists. (Temporary office arrangements were established by Suburban/Petrolane.) The customer base of these companies has been hit very had. For a while, it appeared that one Suburban/Petrolane employee was unaccounted for but that report turned out to be false. Shortly after the storm, crews were out securing gas systems in whatever locations they could reach. In one instance in which regular travel proved impossible, the gas company was forced to travel the long way around-pulling resources out of its Key West district and going north to Homestead. It became necessary in many cases for personnel to purchase cellular phones in order to maintain contact between the office and field crew

  13. An isotherm-based thermodynamic model of multicomponent aqueous solutions, applicable over the entire concentration range.

    Science.gov (United States)

    Dutcher, Cari S; Ge, Xinlei; Wexler, Anthony S; Clegg, Simon L

    2013-04-18

    In previous studies (Dutcher et al. J. Phys. Chem. C 2011, 115, 16474-16487; 2012, 116, 1850-1864), we derived equations for the Gibbs energy, solvent and solute activities, and solute concentrations in multicomponent liquid mixtures, based upon expressions for adsorption isotherms that include arbitrary numbers of hydration layers on each solute. In this work, the long-range electrostatic interactions that dominate in dilute solutions are added to the Gibbs energy expression, thus extending the range of concentrations for which the model can be used from pure liquid solute(s) to infinite dilution in the solvent, water. An equation for the conversion of the reference state for solute activity coefficients to infinite dilution in water has been derived. A number of simplifications are identified, notably the equivalence of the sorption site parameters r and the stoichiometric coefficients of the solutes, resulting in a reduction in the number of model parameters. Solute concentrations in mixtures conform to a modified Zdanovskii-Stokes-Robinson mixing rule, and solute activity coefficients to a modified McKay-Perring relation, when the effects of the long-range (Debye-Hückel) term in the equations are taken into account. Practical applications of the equations to osmotic and activity coefficients of pure aqueous electrolyte solutions and mixtures show both satisfactory accuracy from low to high concentrations, together with a thermodynamically reasonable extrapolation (beyond the range of measurements) to extreme concentration and to the pure liquid solute(s).

  14. A non-hydrostatic flat-bottom ocean model entirely based on Fourier expansion

    Science.gov (United States)

    Wirth, A.

    2005-01-01

    We show how to implement free-slip and no-slip boundary conditions in a three dimensional Boussinesq flat-bottom ocean model based on Fourier expansion. Our method is inspired by the immersed or virtual boundary technique in which the effect of boundaries on the flow field is modeled by a virtual force field. Our method, however, explicitly depletes the velocity on the boundary induced by the pressure, while at the same time respecting the incompressibility of the flow field. Spurious spatial oscillations remain at a negligible level in the simulated flow field when using our technique and no filtering of the flow field is necessary. We furthermore show that by using the method presented here the residual velocities at the boundaries are easily reduced to a negligible value. This stands in contradistinction to previous calculations using the immersed or virtual boundary technique. The efficiency is demonstrated by simulating a Rayleigh impulsive flow, for which the time evolution of the simulated flow is compared to an analytic solution, and a three dimensional Boussinesq simulation of ocean convection. The second instance is taken form a well studied oceanographic context: A free slip boundary condition is applied on the upper surface, the modeled sea surface, and a no-slip boundary condition to the lower boundary, the modeled ocean floor. Convergence properties of the method are investigated by solving a two dimensional stationary problem at different spatial resolutions. The work presented here is restricted to a flat ocean floor. Extensions of our method to ocean models with a realistic topography are discussed.

  15. A Java-based enterprise system architecture for implementing a continuously supported and entirely Web-based exercise solution.

    Science.gov (United States)

    Wang, Zhihui; Kiryu, Tohru

    2006-04-01

    Since machine-based exercise still uses local facilities, it is affected by time and place. We designed a web-based system architecture based on the Java 2 Enterprise Edition that can accomplish continuously supported machine-based exercise. In this system, exercise programs and machines are loosely coupled and dynamically integrated on the site of exercise via the Internet. We then extended the conventional health promotion model, which contains three types of players (users, exercise trainers, and manufacturers), by adding a new player: exercise program creators. Moreover, we developed a self-describing strategy to accommodate a variety of exercise programs and provide ease of use to users on the web. We illustrate our novel design with examples taken from our feasibility study on a web-based cycle ergometer exercise system. A biosignal-based workload control approach was introduced to ensure that users performed appropriate exercise alone.

  16. Entire Agreement Clauses

    DEFF Research Database (Denmark)

    Mitkidis, Katerina; Neumann, Thomas

    2017-01-01

    , it can then be expected that the contract drafting practice will in turn influence national legal rules and the courts’ approach. This effect can already be seen in Danish legal scholarship and its presumption that the judges will not entirely disregard EA clauses, but take a middle road in interpreting......, but also the contract drafting style typical for common law countries. In this way, common law concepts and rules can be transferred to civil law jurisdictions, however, without certainty about the legal effects. This is especially pertinent to boilerplate provisions. On this background, the article aims...

  17. DEMARCATE: Density-based magnetic resonance image clustering for assessing tumor heterogeneity in cancer.

    Science.gov (United States)

    Saha, Abhijoy; Banerjee, Sayantan; Kurtek, Sebastian; Narang, Shivali; Lee, Joonsang; Rao, Ganesh; Martinez, Juan; Bharath, Karthik; Rao, Arvind U K; Baladandayuthapani, Veerabhadran

    2016-01-01

    Tumor heterogeneity is a crucial area of cancer research wherein inter- and intra-tumor differences are investigated to assess and monitor disease development and progression, especially in cancer. The proliferation of imaging and linked genomic data has enabled us to evaluate tumor heterogeneity on multiple levels. In this work, we examine magnetic resonance imaging (MRI) in patients with brain cancer to assess image-based tumor heterogeneity. Standard approaches to this problem use scalar summary measures (e.g., intensity-based histogram statistics) that do not adequately capture the complete and finer scale information in the voxel-level data. In this paper, we introduce a novel technique, DEMARCATE (DEnsity-based MAgnetic Resonance image Clustering for Assessing Tumor hEterogeneity) to explore the entire tumor heterogeneity density profiles (THDPs) obtained from the full tumor voxel space. THDPs are smoothed representations of the probability density function of the tumor images. We develop tools for analyzing such objects under the Fisher-Rao Riemannian framework that allows us to construct metrics for THDP comparisons across patients, which can be used in conjunction with standard clustering approaches. Our analyses of The Cancer Genome Atlas (TCGA) based Glioblastoma dataset reveal two significant clusters of patients with marked differences in tumor morphology, genomic characteristics and prognostic clinical outcomes. In addition, we see enrichment of image-based clusters with known molecular subtypes of glioblastoma multiforme, which further validates our representation of tumor heterogeneity and subsequent clustering techniques.

  18. Statistics-Based Prediction Analysis for Head and Neck Cancer Tumor Deformation

    Directory of Open Access Journals (Sweden)

    Maryam Azimi

    2012-01-01

    Full Text Available Most of the current radiation therapy planning systems, which are based on pre-treatment Computer Tomography (CT images, assume that the tumor geometry does not change during the course of treatment. However, tumor geometry is shown to be changing over time. We propose a methodology to monitor and predict daily size changes of head and neck cancer tumors during the entire radiation therapy period. Using collected patients' CT scan data, MATLAB routines are developed to quantify the progressive geometric changes occurring in patients during radiation therapy. Regression analysis is implemented to develop predictive models for tumor size changes through entire period. The generated models are validated using leave-one-out cross validation. The proposed method will increase the accuracy of therapy and improve patient's safety and quality of life by reducing the number of harmful unnecessary CT scans.

  19. A 3-D model of tumor progression based on complex automata driven by particle dynamics.

    Science.gov (United States)

    Wcisło, Rafał; Dzwinel, Witold; Yuen, David A; Dudek, Arkadiusz Z

    2009-12-01

    The dynamics of a growing tumor involving mechanical remodeling of healthy tissue and vasculature is neglected in most of the existing tumor models. This is due to the lack of efficient computational framework allowing for simulation of mechanical interactions. Meanwhile, just these interactions trigger critical changes in tumor growth dynamics and are responsible for its volumetric and directional progression. We describe here a novel 3-D model of tumor growth, which combines particle dynamics with cellular automata concept. The particles represent both tissue cells and fragments of the vascular network. They interact with their closest neighbors via semi-harmonic central forces simulating mechanical resistance of the cell walls. The particle dynamics is governed by both the Newtonian laws of motion and the cellular automata rules. These rules can represent cell life-cycle and other biological interactions involving smaller spatio-temporal scales. We show that our complex automata, particle based model can reproduce realistic 3-D dynamics of the entire system consisting of the tumor, normal tissue cells, blood vessels and blood flow. It can explain phenomena such as the inward cell motion in avascular tumor, stabilization of tumor growth by the external pressure, tumor vascularization due to the process of angiogenesis, trapping of healthy cells by invading tumor, and influence of external (boundary) conditions on the direction of tumor progression. We conclude that the particle model can serve as a general framework for designing advanced multiscale models of tumor dynamics and it is very competitive to the modeling approaches presented before.

  20. Brain Tumor Segmentation Based on Random Forest

    Directory of Open Access Journals (Sweden)

    László Lefkovits

    2016-09-01

    Full Text Available In this article we present a discriminative model for tumor detection from multimodal MR images. The main part of the model is built around the random forest (RF classifier. We created an optimization algorithm able to select the important features for reducing the dimensionality of data. This method is also used to find out the training parameters used in the learning phase. The algorithm is based on random feature properties for evaluating the importance of the variable, the evolution of learning errors and the proximities between instances. The detection performances obtained have been compared with the most recent systems, offering similar results.

  1. CHONDROID SKULL BASE TUMORS (A REVIEW OF LITERATURE

    Directory of Open Access Journals (Sweden)

    T. G. Gasparyan

    2012-01-01

    Full Text Available Chondroid skull base tumors are a rare and little studied pathology; many problems of their classification, diagnosis and treatment remain to be solved. This group of neoplasms is referred to as bone tumors arising from the cartilaginous tissue of the skull base bones, particularly from the bones formed during chondral osteogenesis. The paper details the clinical picture, X-ray and morphological diagnosis of chondroid tumors. Particular attention is given to surgery and radiotherapy for this category of tumors.

  2. Skull base tumors: a kaleidoscope of challenge.

    Science.gov (United States)

    Khanna, J N; Natrajan, Srivalli; Galinde, Jyotsna

    2014-08-01

    Resection of skull base lesions has always been riddled with problems like inadequate access, proximity to major vessels, dural tears, cranial nerve damage, and infection. Understanding the modular concept of the facial skeleton has led to the development of transfacial swing osteotomies that facilitates resection in a difficult area with minimal morbidity and excellent cosmetic results. In spite of the current trend toward endonasal endoscopic management of skull base tumors, our series presents nine cases of diverse extensive skull base lesions, 33% of which were recurrent. These cases were approached through different transfacial swing osteotomies through the mandible, a midfacial swing, or a zygomaticotemporal osteotomy as dictated by the three-dimensional spatial location of the lesion, and its extent and proximity to vital structures. Access osteotomies ensured complete removal and good results through the most direct and safe route and good vascular control. This reiterated the fact that transfacial approaches still hold a special place in the management of extensive skull base lesions.

  3. Skull base tumors: a comprehensive review of transfacial swing osteotomy approaches.

    Science.gov (United States)

    Moreira-Gonzalez, Andrea; Pieper, Daniel R; Cambra, Jorge Balaguer; Simman, Richard; Jackson, Ian T

    2005-03-01

    Numerous techniques have been proposed for the resection of skull base tumors, each one unique with regard to the region exposed and degree of technical complexity. This study describes the use of transfacial swing osteotomies in accessing lesions located at various levels of the cranial base. Eight patients who underwent transfacial swings for exposure and resection of cranial base lesions between 1996 and 2002 were studied. The mandible was the choice when wide exposure of nasopharyngeal and midline skull base tumors was necessary, especially when they involved the infratemporal fossa. The midfacial swing osteotomy was an option when access to the entire clivus was necessary. An orbital swing approach was used to access large orbital tumors lying inferior to the optic nerve and posterior to the globe, a region that is often difficult to visualize. Gross total tumor excision was possible in all patients. Six patients achieved disease control and two had recurrences. The complications of cerebrospinal fluid leak, infection, hematoma, or cranial nerve damage did not occur. After surgery, some patients experienced temporary symptoms caused by local swelling. The aesthetic result was considered good. Transfacial swing osteotomies provide a wide exposure to tumors that occur in the central skull base area. Excellent knowledge of the detailed anatomy of this region is paramount to the success of this surgery. The team concept is essential; it is built around the craniofacial surgeon and an experienced skull base neurosurgeon.

  4. Silver(I)-Mediated Base Pairs in DNA Sequences Containing 7-Deazaguanine/Cytosine: towards DNA with Entirely Metallated Watson-Crick Base Pairs.

    Science.gov (United States)

    Méndez-Arriaga, José M; Maldonado, Carmen R; Dobado, José A; Galindo, Miguel A

    2018-03-26

    DNA sequences comprising noncanonical 7-deazaguanine ( 7C G) and canonical cytosine (C) are capable of forming Watson-Crick base pairs via hydrogen bonds as well as silver(I)-mediated base pairs by coordination to central silver(I) ions. Duplexes I and II containing 7C G and C have been synthesized and characterized. The incorporation of silver(I) ions into these duplexes has been studied by means of temperature-dependent UV spectroscopy, circular dichroism, and DFT calculations. The results suggest the formation of DNA molecules comprising contiguous metallated 7C G-Ag I -C Watson-Crick base pairs that preserve the original B-type conformation. Furthermore, additional studies performed on duplex III indicated that, in the presence of Ag I ions, 7C G-C and 7C A-T Watson-Crick base pairs ( 7C A, 7-deazadenine; T, thymine) can be converted to metallated 7C G-Ag I -C and 7C A-Ag I -T base pairs inside the same DNA molecule whilst maintaining its initial double helix conformation. These findings are very important for the development of customized silver-DNA nanostructures based on a Watson-Crick complementarity pattern. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Theranostic GO-based nanohybrid for tumor induced imaging and potential combinational tumor therapy.

    Science.gov (United States)

    Qin, Si-Yong; Feng, Jun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Liu, Xiang-Ji; Luo, Guo-Feng; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-02-12

    Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping.

    Science.gov (United States)

    Stachler, Matthew; Jia, Yonghui; Sharaf, Nematullah; Wade, Jacqueline; Longtine, Janina; Garcia, Elizabeth; Sholl, Lynette M

    2015-01-01

    Molecular testing of tumors from formalin-fixed paraffin-embedded (FFPE) tissue blocks is central to clinical practice; however, it requires histology support and increases test turnaround time. Prospective fresh frozen tissue collection requires special handling, additional storage space, and may not be feasible for small specimens. Filter paper-based collection of tumor DNA reduces the need for histology support, requires little storage space, and preserves high-quality nucleic acid. We investigated the performance of tumor smears on filter paper in solid tumor genotyping, as compared with paired FFPE samples. Whatman FTA Micro Card (FTA preps) smears were prepared from 21 fresh tumor samples. A corresponding cytology smear was used to assess tumor cellularity and necrosis. DNA was isolated from FTA preps and FFPE core samples using automated methods and quantified using SYBR green dsDNA detection. Samples were genotyped for 471 mutations on a mass spectrophotometry-based platform (Sequenom). DNA concentrations from FTA preps and FFPE correlated for untreated carcinomas but not for mesenchymal tumors (Spearman σ=0.39 and σ=-0.1, respectively). Average DNA concentrations were lower from FTA preps as compared with FFPE, but DNA quality was higher with less fragmentation. Seventy-six percent of FTA preps and 86% of FFPE samples generated adequate DNA for genotyping. FTA preps tended to perform poorly for collection of DNA from pretreated carcinomas and mesenchymal neoplasms. Of the 16 paired DNA samples that were genotyped, 15 (94%) gave entirely concordant results. Filter paper-based sample preservation is a feasible alternative to FFPE for use in automated, high-throughput genotyping of carcinomas.

  7. Image-Based Monitoring of Magnetic Resonance-Guided Thermoablative Therapies for Liver Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rempp, Hansjoerg, E-mail: hansjoerg.rempp@med.uni-tuebingen.de; Clasen, Stephan [Eberhard Karls University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany); Pereira, Philippe L. [SLK-Kliniken, Clinic for Radiology, Nuclear Medicine, and Minimal Invasive Therapies (Germany)

    2012-12-15

    Minimally invasive treatment options for liver tumor therapy have been increasingly used during the last decade because their benefit has been proven for primary and inoperable secondary liver tumors. Among these, radiofrequency ablation has gained widespread consideration. Optimal image-guidance offers precise anatomical information, helps to position interventional devices, and allows for differentiation between already-treated and remaining tumor tissue. Patient safety and complete ablation of the entire tumor are the overriding objectives of tumor ablation. These may be achieved most elegantly with magnetic resonance (MR)-guided therapy, where monitoring can be performed based on precise soft-tissue imaging and additional components, such as diffusion-weighted imaging and temperature mapping. New MR scanner types and newly developed sequence techniques have enabled MR-guided intervention to move beyond the experimental phase. This article reviews the current role of MR imaging in guiding radiofrequency ablation. Signal characteristics of primary and secondary liver tumors are identified, and signal alteration during therapy is described. Diffusion-weighted imaging (DWI) and temperature mapping as special components of MR therapy monitoring are introduced. Practical information concerning coils, sequence selection, and parameters, as well as sequence gating, is given. In addition, sources of artifacts are identified and techniques to decrease them are introduced, and the characteristic signs of residual tumor in T1-, T2-, and DWI are described. We hope to enable the reader to choose MR sequences that allow optimal therapy monitoring depending on the initial signal characteristics of the tumor as well as its size and location in the liver.

  8. Image-Based Monitoring of Magnetic Resonance-Guided Thermoablative Therapies for Liver Tumors

    International Nuclear Information System (INIS)

    Rempp, Hansjörg; Clasen, Stephan; Pereira, Philippe L.

    2012-01-01

    Minimally invasive treatment options for liver tumor therapy have been increasingly used during the last decade because their benefit has been proven for primary and inoperable secondary liver tumors. Among these, radiofrequency ablation has gained widespread consideration. Optimal image-guidance offers precise anatomical information, helps to position interventional devices, and allows for differentiation between already-treated and remaining tumor tissue. Patient safety and complete ablation of the entire tumor are the overriding objectives of tumor ablation. These may be achieved most elegantly with magnetic resonance (MR)-guided therapy, where monitoring can be performed based on precise soft-tissue imaging and additional components, such as diffusion-weighted imaging and temperature mapping. New MR scanner types and newly developed sequence techniques have enabled MR-guided intervention to move beyond the experimental phase. This article reviews the current role of MR imaging in guiding radiofrequency ablation. Signal characteristics of primary and secondary liver tumors are identified, and signal alteration during therapy is described. Diffusion-weighted imaging (DWI) and temperature mapping as special components of MR therapy monitoring are introduced. Practical information concerning coils, sequence selection, and parameters, as well as sequence gating, is given. In addition, sources of artifacts are identified and techniques to decrease them are introduced, and the characteristic signs of residual tumor in T1-, T2-, and DWI are described. We hope to enable the reader to choose MR sequences that allow optimal therapy monitoring depending on the initial signal characteristics of the tumor as well as its size and location in the liver.

  9. Lung tumor tracking in fluoroscopic video based on optical flow

    International Nuclear Information System (INIS)

    Xu Qianyi; Hamilton, Russell J.; Schowengerdt, Robert A.; Alexander, Brian; Jiang, Steve B.

    2008-01-01

    Respiratory gating and tumor tracking for dynamic multileaf collimator delivery require accurate and real-time localization of the lung tumor position during treatment. Deriving tumor position from external surrogates such as abdominal surface motion may have large uncertainties due to the intra- and interfraction variations of the correlation between the external surrogates and internal tumor motion. Implanted fiducial markers can be used to track tumors fluoroscopically in real time with sufficient accuracy. However, it may not be a practical procedure when implanting fiducials bronchoscopically. In this work, a method is presented to track the lung tumor mass or relevant anatomic features projected in fluoroscopic images without implanted fiducial markers based on an optical flow algorithm. The algorithm generates the centroid position of the tracked target and ignores shape changes of the tumor mass shadow. The tracking starts with a segmented tumor projection in an initial image frame. Then, the optical flow between this and all incoming frames acquired during treatment delivery is computed as initial estimations of tumor centroid displacements. The tumor contour in the initial frame is transferred to the incoming frames based on the average of the motion vectors, and its positions in the incoming frames are determined by fine-tuning the contour positions using a template matching algorithm with a small search range. The tracking results were validated by comparing with clinician determined contours on each frame. The position difference in 95% of the frames was found to be less than 1.4 pixels (∼0.7 mm) in the best case and 2.8 pixels (∼1.4 mm) in the worst case for the five patients studied.

  10. Proton therapy for tumors of the skull base

    Energy Technology Data Exchange (ETDEWEB)

    Munzenrider, J.E.; Liebsch, N.J. [Dept. of Radiation Oncology, Harvard Univ. Medical School, Boston, MA (United States)

    1999-06-01

    Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. (orig.)

  11. Proton therapy for tumors of the skull base

    International Nuclear Information System (INIS)

    Munzenrider, J.E.; Liebsch, N.J.

    1999-01-01

    Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. (orig.)

  12. The class of n-entire operators

    International Nuclear Information System (INIS)

    Silva, Luis O; Toloza, Julio H

    2013-01-01

    We introduce a classification of simple, regular, closed symmetric operators with deficiency indices (1, 1) according to a geometric criterion that extends the classical notions of entire operators and entire operators in the generalized sense due to M G Krein. We show that these classes of operators have several distinctive properties, some of them related to the spectra of their canonical self-adjoint extensions. In particular, we provide necessary and sufficient conditions on the spectra of two canonical self-adjoint extensions of an operator for it to belong to one of our classes. Our discussion is based on some recent results in the theory of de Branges spaces. (paper)

  13. Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base

    International Nuclear Information System (INIS)

    Combs, Stephanie E.; Kessel, Kerstin; Habermehl, Daniel; Debus, Jurgen; Haberer, Thomas; Jaekel, Oliver

    2013-01-01

    To analyze clinical concepts, toxicity and treatment outcome in patients with brain and skull base tumors treated with photons and particle therapy. Material and methods: In total 260 patients with brain tumors and tumors of the skull base were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and randomized within prospective clinical trials as well as bony or soft tissue tumors are not included in this analysis. Treatment was delivered as protons, carbon ions, or combinations of photons and a carbon ion boost. All patients are included in a tight follow-up program. The median follow-up time is 12 months (range 2-39 months). Results: Main histologies included meningioma (n = 107) for skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment could be completed without any unexpected severe toxicities. No side effects > CTC Grade III were observed. To date, no severe late toxicities were observed, however, for endpoints such as secondary malignancies or neuro cognitive side effects follow-up time still remains too short. Local recurrences were mainly seen in the group of high-grade gliomas or atypical meningiomas; for benign skull base meningiomas, to date, no recurrences were observed during follow-up. Conclusion: The specific benefit of particle therapy will potentially reduce the risk of secondary malignancies as well as improve neuro cognitive outcome and quality of life (QOL); thus, longer follow-up will be necessary to confirm these endpoints. Indication-specific trials on meningiomas and gliomas are underway to elucidate the role of protons and carbon ions in these indications

  14. Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephanie E.; Kessel, Kerstin; Habermehl, Daniel; Debus, Jurgen [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)], e-mail: Stephanie.Combs@med.uni-heidelberg.de; Haberer, Thomas [Heidelberger Ionenstrahl Therapiezentrum (HIT), Heidelberg (Germany); Jaekel, Oliver [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); Heidelberger Ionenstrahl Therapiezentrum (HIT), Heidelberg (Germany)

    2013-10-15

    To analyze clinical concepts, toxicity and treatment outcome in patients with brain and skull base tumors treated with photons and particle therapy. Material and methods: In total 260 patients with brain tumors and tumors of the skull base were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and randomized within prospective clinical trials as well as bony or soft tissue tumors are not included in this analysis. Treatment was delivered as protons, carbon ions, or combinations of photons and a carbon ion boost. All patients are included in a tight follow-up program. The median follow-up time is 12 months (range 2-39 months). Results: Main histologies included meningioma (n = 107) for skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment could be completed without any unexpected severe toxicities. No side effects > CTC Grade III were observed. To date, no severe late toxicities were observed, however, for endpoints such as secondary malignancies or neuro cognitive side effects follow-up time still remains too short. Local recurrences were mainly seen in the group of high-grade gliomas or atypical meningiomas; for benign skull base meningiomas, to date, no recurrences were observed during follow-up. Conclusion: The specific benefit of particle therapy will potentially reduce the risk of secondary malignancies as well as improve neuro cognitive outcome and quality of life (QOL); thus, longer follow-up will be necessary to confirm these endpoints. Indication-specific trials on meningiomas and gliomas are underway to elucidate the role of protons and carbon ions in these indications.

  15. Nanobody-based cancer therapy of solid tumors

    NARCIS (Netherlands)

    Kijanka, Marta|info:eu-repo/dai/nl/328212792; Dorresteijn, Bram|info:eu-repo/dai/nl/31401635X; Oliveira, Sabrina; van Bergen en Henegouwen, Paul M P|info:eu-repo/dai/nl/071919481

    The development of tumor-targeted therapies using monoclonal antibodies has been successful during the last 30 years. Nevertheless, the efficacy of antibody-based therapy is still limited and further improvements are eagerly awaited. One of the promising novel developments that may overcome the

  16. A system for tumor heterogeneity evaluation and diagnosis based on tumor markers measured routinely in the laboratory.

    Science.gov (United States)

    Hui, Liu; Rixv, Liu; Xiuying, Zhou

    2015-12-01

    To develop an efficient and reliable approach to estimate tumor heterogeneity and improve tumor diagnosis using multiple tumor markers measured routinely in the clinical laboratory. A total of 161 patients with different cancers were recruited as the cancer group, and 91 patients with non-oncological conditions were required as the non-oncological disease group. The control group comprised 90 randomly selected healthy subjects. AFP, CEA, CYFRA, CA125, CA153, CA199, CA724, and NSE levels were measured in all these subjects with a chemiluminescent microparticle immunoassay. The tumor marker with the maximum S/CO value (sample test value:cutoff value for discriminating individuals with and without tumors) was considered as a specific tumor marker (STM) for an individual. Tumor heterogeneity index (THI)=N/P (N: number of STMs; P: percentage of individuals with STMs in a certain tumor population) was used to quantify tumor heterogeneity: high THI indicated high tumor heterogeneity. The tumor marker index (TMI), TMI = STM×(number of positive tumor markers+1), was used for diagnosis. The THIs of lung, gastric, and liver cancers were 8.33, 9.63, and 5.2, respectively, while the ROC-areas under the curve for TMI were 0.862, 0.809, and 0.966. In this study, we developed a novel index for tumor heterogeneity based on the expression of various routinely evaluated serum tumor markers. Development of an evaluation system for tumor heterogeneity on the basis of this index could provide an effective diagnostic tool for some cancers. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  17. Margin Evaluation in the Presence of Deformation, Rotation, and Translation in Prostate and Entire Seminal Vesicle Irradiation With Daily Marker-Based Setup Corrections

    International Nuclear Information System (INIS)

    Mutanga, Theodore F.; Boer, Hans C.J. de; Wielen, Gerard J. van der; Hoogeman, Mischa S.; Incrocci, Luca; Heijmen, Ben J.M.

    2011-01-01

    Purpose: To develop a method for margin evaluation accounting for all measured displacements during treatment of prostate cancer. Methods and Materials: For 21 patients treated with stereographic targeting marker-based online translation corrections, dose distributions with varying margins and gradients were created. Sets of possible cumulative delivered dose distributions were simulated by moving voxels and accumulating dose per voxel. Voxel motion was simulated consistent with measured distributions of systematic and random displacements due to stereographic targeting inaccuracies, deformation, rotation, and intrafraction motion. The method of simulation maintained measured correlation of voxel motions due to organ deformation. Results: For the clinical target volume including prostate and seminal vesicles (SV), the probability that some part receives <95% of the prescribed dose, the changes in minimum dose, and volume receiving 95% of prescription dose compared with planning were 80.5% ± 19.2%, 9.0 ± 6.8 Gy, and 3.0% ± 3.7%, respectively, for the smallest studied margins (3 mm prostate, 5 mm SV) and steepest dose gradients. Corresponding values for largest margins (5 mm prostate, 8 mm SV) with a clinical intensity-modulated radiotherapy dose distribution were 46.5% ± 34.7%, 6.7 ± 5.8 Gy, and 1.6% ± 2.3%. For prostate-only clinical target volume, the values were 51.8% ± 17.7%, 3.3 ± 1.6 Gy, and 0.6% ± 0.5% with the smallest margins and 5.2% ± 7.4%, 1.8 ± 0.9 Gy, and 0.1% ± 0.1% for the largest margins. Addition of three-dimensional rotation corrections only improved these values slightly. All rectal planning constraints were met in the actual reconstructed doses for all studied margins. Conclusion: We developed a system for margin validation in the presence of deformations. In our population, a 5-mm margin provided sufficient dosimetric coverage for the prostate. In contrast, an 8-mm SV margin was still insufficient owing to deformations. Addition of

  18. [Extensive tumor of the skull base: sphenoid sinus adenocarcinoma].

    Science.gov (United States)

    Kallel, Souha; Sellami, Moncef

    2017-01-01

    We report a rare case of adenocarcinoma of the sphenoid sinus manifesting as extended skull base tumor. The patient included in the study was a 42-year old woman presenting with unilateral right symptomatology consisting of nasal obstruction, diplopia and hemifacial neuralgias. Clinical examination showed paralysis of the cranial nerve pairs V and VI. Brain scanner showed voluminous heterogeneous sphenoid and clival mass reaching the right cavernous sinus, with a peripheral tissue component at the level of the sphenoid sinus. Biopsy was performed under general anesthesia, through endonasal sphenoidotomy approach. Histological examination showed non-intestinal adenocarcinoma. The patient died due to impaired general condition occurred during examinations. Skull base adenocarcinomas mainly occur in the ethmoid bone. Sphenoid origin is exceptional. Radiological appearance is not specific and suggests malignancy. Diagnosis should be suspected in patients with aggressive tumor, even when it occurs in the midline skull base.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Oroji, Amin; Omar, Mohd bin [Institute of Mathematical Sciences, Faculty of Science University of Malaya, 50603 Kuala Lumpur, Malaysia amin.oroji@siswa.um.edu.my, mohd@um.edu.my (Malaysia); Yarahmadian, Shantia [Mathematics Department Mississippi State University, USA Syarahmadian@math.msstate.edu (United States)

    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.

  1. Proton radiotherapy in management of pediatric base of skull tumors

    International Nuclear Information System (INIS)

    Hug, Eugen B.; Sweeney, Reinhart A.; Nurre, Pamela M.; Holloway, Kitty C.; Slater, Jerry D.; Munzenrider, John E.

    2002-01-01

    Purpose: Primary skull base tumors of the developing child are rare and present a formidable challenge to both surgeons and radiation oncologists. Gross total resection with negative margins is rarely achieved, and the risks of functional, structural, and cosmetic deficits limit the radiation dose using conventional radiation techniques. Twenty-nine children and adolescents treated with conformal proton radiotherapy (proton RT) were analyzed to assess treatment efficacy and safety. Methods and Materials: Between July 1992 and April 1999, 29 patients with mesenchymal tumors underwent fractionated proton (13 patients) or fractionated combined proton and photon (16 patients) irradiation. The age at treatment ranged from 1 to 19 years (median 12); 14 patients were male and 15 female. Tumors were grouped as malignant or benign. Twenty patients had malignant histologic findings, including chordoma (n=10), chondrosarcoma (n=3), rhabdomyosarcoma (n=4), and other sarcomas (n=3). Target doses ranged between 50.4 and 78.6 Gy/cobalt Gray equivalent (CGE), delivered at doses of 1.8-2.0 Gy/CGE per fraction. The benign histologic findings included giant cell tumors (n=6), angiofibromas (n=2), and chondroblastoma (n=1). RT doses for this group ranged from 45.0 to 71.8 Gy/CGE. Despite maximal surgical resection, 28 (97%) of 29 patients had gross disease at the time of proton RT. Follow-up after proton RT ranged from 13 to 92 months (mean 40). Results: Of the 20 patients with malignant tumors, 5 (25%) had local failure; 1 patient had failure in the surgical access route and 3 patients developed distant metastases. Seven patients had died of progressive disease at the time of analysis. Local tumor control was maintained in 6 (60%) of 10 patients with chordoma, 3 (100%) of 3 with chondrosarcoma, 4 (100%) of 4 with rhabdomyosarcoma, and 2 (66%) of 3 with other sarcomas. The actuarial 5-year local control and overall survival rate was 72% and 56%, respectively, and the overall survival

  2. SU-G-BRA-04: Simulation of Errors in Maximal Intensity Projection (MIP)-Based Lung Tumor Internal Target Volumes (ITV) Using Real-Time 2D MRI and Deformable Image Registration Based Lung Tumor Tracking

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, D; Kishan, A; Santhanam, A; Min, Y; O’Connell, D; Lamb, J; Cao, M; Agazaryan, N; Yang, Y; Lee, P; Low, D [University of California, Los Angeles, Ca (United States)

    2016-06-15

    Purpose: To evaluate the effect of inter- and intra-fractional tumor motion on the error in four-dimensional computed tomography (4DCT) maximal intensity projection (MIP)–based lung tumor internal target volumes (ITV), using deformable image registration of real-time 2D-sagital cine-mode MRI acquired during lung SBRT treatments. Methods: Five lung tumor patients underwent free breathing SBRT treatment on the ViewRay, with dose prescribed to PTV (4DCT MIP-based ITV+3–6mm margin). Sagittal slice cine-MR images (3.5×3.5mm pixels) were acquired through the center of the tumor at 4 frames per second throughout the treatments (3–4 fractions of 21–32 minutes duration). Tumor GTVs were contoured on the first frame of the cine and tracked throughout the treatment using off-line optical-flow based deformable registration implemented on a GPU cluster. Pseudo-4DCT MIP-based ITVs were generated from MIPs of the deformed GTV contours limited to short segments of image data. All possible pseudo-4DCT MIP-based ITV volumes were generated with 1s resolution and compared to the ITV volume of the entire treatment course. Varying pseudo-4DCT durations from 10-50s were analyzed. Results: Tumors were covered in their entirety by PTV in the patients analysed here. However, pseudo-4DCT based ITV volumes were observed that were as small as 29% of the entire treatment-ITV, depending on breathing irregularity and the duration of pseudo-4DCT. With an increase in duration of pseudo-4DCT from 10–50s the minimum volume acquired from 95% of all pseudo-4DCTs increased from 62%–81% of the treatment ITV. Conclusion: A 4DCT MIP-based ITV offers a ‘snap-shot’ of breathing motion for the brief period of time the tumor is imaged on a specific day. Real time MRI over prolonged periods of time and over multiple treatment fractions shows that the accuracy of this snap-shot varies according to inter- and intra-fractional tumor motion. Further work is required to investigate the dosimetric

  3. SU-G-BRA-04: Simulation of Errors in Maximal Intensity Projection (MIP)-Based Lung Tumor Internal Target Volumes (ITV) Using Real-Time 2D MRI and Deformable Image Registration Based Lung Tumor Tracking

    International Nuclear Information System (INIS)

    Thomas, D; Kishan, A; Santhanam, A; Min, Y; O’Connell, D; Lamb, J; Cao, M; Agazaryan, N; Yang, Y; Lee, P; Low, D

    2016-01-01

    Purpose: To evaluate the effect of inter- and intra-fractional tumor motion on the error in four-dimensional computed tomography (4DCT) maximal intensity projection (MIP)–based lung tumor internal target volumes (ITV), using deformable image registration of real-time 2D-sagital cine-mode MRI acquired during lung SBRT treatments. Methods: Five lung tumor patients underwent free breathing SBRT treatment on the ViewRay, with dose prescribed to PTV (4DCT MIP-based ITV+3–6mm margin). Sagittal slice cine-MR images (3.5×3.5mm pixels) were acquired through the center of the tumor at 4 frames per second throughout the treatments (3–4 fractions of 21–32 minutes duration). Tumor GTVs were contoured on the first frame of the cine and tracked throughout the treatment using off-line optical-flow based deformable registration implemented on a GPU cluster. Pseudo-4DCT MIP-based ITVs were generated from MIPs of the deformed GTV contours limited to short segments of image data. All possible pseudo-4DCT MIP-based ITV volumes were generated with 1s resolution and compared to the ITV volume of the entire treatment course. Varying pseudo-4DCT durations from 10-50s were analyzed. Results: Tumors were covered in their entirety by PTV in the patients analysed here. However, pseudo-4DCT based ITV volumes were observed that were as small as 29% of the entire treatment-ITV, depending on breathing irregularity and the duration of pseudo-4DCT. With an increase in duration of pseudo-4DCT from 10–50s the minimum volume acquired from 95% of all pseudo-4DCTs increased from 62%–81% of the treatment ITV. Conclusion: A 4DCT MIP-based ITV offers a ‘snap-shot’ of breathing motion for the brief period of time the tumor is imaged on a specific day. Real time MRI over prolonged periods of time and over multiple treatment fractions shows that the accuracy of this snap-shot varies according to inter- and intra-fractional tumor motion. Further work is required to investigate the dosimetric

  4. Mesenchymal stem cell 1 (MSC1-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ruth S Waterman

    Full Text Available Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed MSC1 and MSC2.Here we tested the in vitro and in vivo stability of MSC1 and MSC2 phenotypes as well as their effects on tumor growth and spread. In vitro co-culture of MSC1 with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays. Co-culture of MSC1 and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCs- and MSC2-treated animals in which tumor growth and spread was increased. Also, in contrast to these groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation.These observations indicate that the MSC1 and MSC2 phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease.

  5. Multitriggered Tumor-Responsive Drug Delivery Vehicles Based on Protein and Polypeptide Coassembly for Enhanced Photodynamic Tumor Ablation.

    Science.gov (United States)

    Zhang, Ning; Zhao, Fenfang; Zou, Qianli; Li, Yongxin; Ma, Guanghui; Yan, Xuehai

    2016-11-01

    Tumor-responsive nanocarriers are highly valuable and demanded for smart drug delivery particularly in the field of photodynamic therapy (PDT), where a quick release of photosensitizers in tumors is preferred. Herein, it is demonstrated that protein-based nanospheres, prepared by the electrostatic assembly of proteins and polypeptides with intermolecular disulfide cross-linking and surface polyethylene glycol coupling, can be used as versatile tumor-responsive drug delivery vehicles for effective PDT. These nanospheres are capable of encapsulation of various photosensitizers including Chlorin e6 (Ce6), protoporphyrin IX, and verteporfin. The Chlorin e6-encapsulated nanospheres (Ce6-Ns) are responsive to changes in pH, redox potential, and proteinase concentration, resulting in multitriggered rapid release of Ce6 in an environment mimicking tumor tissues. In vivo fluorescence imaging results indicate that Ce6-Ns selectively accumulate near tumors and the quick release of Ce6 from Ce6-Ns can be triggered by tumors. In tumors the fluorescence of released Ce6 from Ce6-Ns is observed at 0.5 h postinjection, while in normal tissues the fluorescence appeared at 12 h postinjection. Tumor ablation is demonstrated by in vivo PDT using Ce6-Ns and the biocompatibility of Ce6-Ns is evident from the histopathology imaging, confirming the enhanced in vivo PDT efficacy and the biocompatibility of the assembled drug delivery vehicles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Automatización de un registro hospitalario de tumores Automatization of a hospital-based tumor registry

    Directory of Open Access Journals (Sweden)

    Josepa Ribes

    2005-06-01

    Full Text Available Introducción: El Instituto Catalán de Oncología automatizó los procedimientos manuales de captación de la información de las bases de datos del alta hospitalaria (AH y anatomía patológica (APA mediante una aplicación informática (ASEDAT con el objetivo de aumentar la fiabilidad de los datos y reducir los costes del Registro Hospitalario de Tumores (RHT. Material y Método: ASEDAT detecta los tumores incidentes del centro a partir de las bases de datos de APA y de las AH mediante la selección de la información básica para cada uno de ellos. Se resolvió el RHT para el período 1999-2000 mediante el procedimiento manual y automatizado, y se compararon entre sí los resultados. Resultados: Se detectaron 10.498 pacientes oncológicos. La resolución manual detectó 8.309 tumores incidentes y 2.374 tumores prevalentes. ASEDAT resolvió automáticamente 8.901 pacientes (84,8%, en los cuales se detectaron 8.367 tumores incidentes, 58 tumores más que con el procedimiento manual. La validación de la concordancia se realizó en los tumores incidentes detectados por ambos métodos (7.063 tumores. En 6.185 tumores (87,6%, la información coincidió en todas las variables. De los tumores discordantes, 692 (9,8% fueron generados por el personal del RHT en la resolución manual y el resto (n = 186; 2,6% por la aplicación (resolución automática. Conclusiones: La automatización de un registro de cáncer es posible siempre y cuando el centro disponga de las bases de datos de APA y AH codificadas e informatizadas.Introduction: To increase data reliability and reduce the costs associated with the HTR, the Catalan Institute of Oncology programmed the manual procedures of data collection from databases by means of a computer application (ASEDAT. Material and method: ASEDAT detects the incident tumors of the registry from the databases of the pathology records (PR and discharge records (DR and selects the basic information from both databases. Data

  7. Schroedinger--Dirac spaces of entire functions

    International Nuclear Information System (INIS)

    De Branges, L.

    1977-01-01

    A study is made of some Hilbert spaces of entire function which appear in the quantum mechanical theory of the hydrogen atoms. These spaces are examples in the theory of Hilbert spaces whose elements are entire functions and which have certain given properties. 1 reference

  8. Pattern of malignant tumors in children: a hospital based study

    International Nuclear Information System (INIS)

    Khan, S.M.; Nasreen, S.; Zai, S.

    2001-01-01

    From 1990 to 1999 data from 32743 cancer patients (males 18502, females 14241) were analyzed to know the frequency of the most common cancers in local and well as well as afghan refugees. There were 3760 children with biopsy proven cancers 2910 belonged to the north-west frontier province (NWFP), while the remaining 850 were Afghan refugees. Among children of NWFP male were 1945 (67%) and 965(33%) females. In Afghan children, males were 570(67%) and females were 280(33%). The most common tumors in children of NWFP were lymphoid leukemia, lymphoma, tumors of the central nervous system (CNS), myeloid leukemia, soft tissue sarcoma wilms, tumours, retinoblastoma, bone tumor neuroblastoma, and ovarian tumors. Whereas Afghan children had Lymphoid leukemia, lymphoma, myeloid leukemia, wilms, tumor, retinoblastoma, tumors of soft tissue bones CNS, neuroblastoma and ovarian tumors. (author)

  9. Endocrine tumors other than thyroid tumors

    International Nuclear Information System (INIS)

    Takeichi, Norio; Dohi, Kiyohiko

    1992-01-01

    This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

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

    Science.gov (United States)

    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.

  11. Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling.

    Science.gov (United States)

    Karthik, Govindasamy-Muralidharan; Rantalainen, Mattias; Stålhammar, Gustav; Lövrot, John; Ullah, Ikram; Alkodsi, Amjad; Ma, Ran; Wedlund, Lena; Lindberg, Johan; Frisell, Jan; Bergh, Jonas; Hartman, Johan

    2017-11-29

    Transcriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics. In this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications. Molecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications. Our results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.

  12. Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

    Energy Technology Data Exchange (ETDEWEB)

    Malinowski, Kathleen T. [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); McAvoy, Thomas J. [Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); Department of Chemical and Biomolecular Engineering and Institute of Systems Research, University of Maryland, College Park, MD (United States); George, Rohini [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Dieterich, Sonja [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); D' Souza, Warren D., E-mail: wdsou001@umaryland.edu [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States)

    2012-04-01

    Purpose: To investigate the effect of tumor site, measurement precision, tumor-surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor-surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor-surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3-3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

  13. Changing Histopathological Diagnostics by Genome-Based Tumor Classification

    Directory of Open Access Journals (Sweden)

    Michael Kloth

    2014-05-01

    Full Text Available Traditionally, tumors are classified by histopathological criteria, i.e., based on their specific morphological appearances. Consequently, current therapeutic decisions in oncology are strongly influenced by histology rather than underlying molecular or genomic aberrations. The increase of information on molecular changes however, enabled by the Human Genome Project and the International Cancer Genome Consortium as well as the manifold advances in molecular biology and high-throughput sequencing techniques, inaugurated the integration of genomic information into disease classification. Furthermore, in some cases it became evident that former classifications needed major revision and adaption. Such adaptations are often required by understanding the pathogenesis of a disease from a specific molecular alteration, using this molecular driver for targeted and highly effective therapies. Altogether, reclassifications should lead to higher information content of the underlying diagnoses, reflecting their molecular pathogenesis and resulting in optimized and individual therapeutic decisions. The objective of this article is to summarize some particularly important examples of genome-based classification approaches and associated therapeutic concepts. In addition to reviewing disease specific markers, we focus on potentially therapeutic or predictive markers and the relevance of molecular diagnostics in disease monitoring.

  14. Brainstem tolerance to conformal radiotherapy of skull base tumors

    International Nuclear Information System (INIS)

    Debus, J.; Hug, E.B.; Munzenrider, J.E.; Liebsch, N.J.; O'Farrell, D.; Efird, J.; Daly, W.; Suit, H.D.

    1996-01-01

    Purpose/Objective: Brainstem tolerance to inhomogenous radiation doses applied by modern conformal radiotherapy has not yet been examined. The aim of this study was to analyse the incidence of brainstem toxicity in patients treated for skull base tumors with high dose conformal radiotherapy. Materials and Methods: Between 1974 and 1995, 367 patients with chordomas (n=195) and chondrosarcomas (n=172) of the base of skull have been treated with combined megavoltage photon and 160 MeV proton radiotherapy. All patients had previously undergone biopsy, subtotal or total tumor removal. 104 patients had two or more surgical procedures before radiotherapy. Following 3D treatment planning with delineation of target volumes and critical non-target structures, dose distributions and dose volume histograms were calculated [at the time of treatment delivery]. Radiotherapy was given once a day, 1.8 Gy or CGE (Cobalt Gy Equivalent: Proton Gy X 1.1) per fraction, 5 fractions per week, with prescribed target doses ranging from 63 CGE to 79.2 CGE (mean = 67.8 CGE). Doses to the brainstem surface were limited to ≤64 CGE and to the brainstem center to ≤53 CGE. Dose distributions were developed to limit dose to brainstem surface and center; current plans limit dose to surface and center to ≤64 CGE and ≤53 CGE, respectively. Brainstem toxicity was scored according to the RTOG grading system. Results: Follow-up ranged from 6 months to 21.4 years (mean = 42.5 months). Brainstem symptoms, attributable to the treatment, developed in 17 of 282 patients with local tumor control (6.0%), resulting in death of three patients. The mean time to onset of symptoms was 17 months (range: 4.5 to 177 months). These symptoms appeared in 89.5% within 3 years. Grading of the brainstem toxicity is listed in table 1. Actuarial rates of 5 and 10 year toxicity free survival were 87% and 82% respectively. Increased risk of brainstem toxicity was significantly associated with maximum brainstem dose

  15. Entire hemithorax irradiation for Masaoka stage IVa thymomas

    Science.gov (United States)

    Soares, André; Louro, Luís Vasco; Almeida, Marta; Sousa, Olga

    2012-01-01

    Thymomas are rare neoplasms that have an indolent growth with a preferentially intra-thoracic dissemination pattern. Surgery is currently the standard treatment of thymomas; however radiotherapy is often used in an adjuvant setting due to a high sensitivity of these tumors to such treatment. Postoperative entire hemithoracic irradiation has been used in selected Masaoka stage IVa cases after complete surgical excision of metastatic lesions. In the present article, the authors report three cases of Masaoka stage IVa thymoma that underwent entire hemithorax irradiation after surgical excision of metastatic lesions. The first two patients presented as stage IVa thymomas. The third case consisted of a pleural recurrence of a thymoma. Hemithoracic irradiation with low doses has been used by different authors; the available data shows that it is a well-tolerated treatment that could potentially lead to better loco-regional control and increased overall survival. PMID:24377042

  16. mRNA-based vaccines synergize with radiation therapy to eradicate established tumors

    International Nuclear Information System (INIS)

    Fotin-Mleczek, Mariola; Zanzinger, Kai; Heidenreich, Regina; Lorenz, Christina; Kowalczyk, Aleksandra; Kallen, Karl-Josef; Huber, Stephan M

    2014-01-01

    The eradication of large, established tumors by active immunotherapy is a major challenge because of the numerous cancer evasion mechanisms that exist. This study aimed to establish a novel combination therapy consisting of messenger RNA (mRNA)-based cancer vaccines and radiation, which would facilitate the effective treatment of established tumors with aggressive growth kinetics. The combination of a tumor-specific mRNA-based vaccination with radiation was tested in two syngeneic tumor models, a highly immunogenic E.G7-OVA and a low immunogenic Lewis lung cancer (LLC). The molecular mechanism induced by the combination therapy was evaluated via gene expression arrays as well as flow cytometry analyses of tumor infiltrating cells. In both tumor models we demonstrated that a combination of mRNA-based immunotherapy with radiation results in a strong synergistic anti-tumor effect. This was manifested as either complete tumor eradication or delay in tumor growth. Gene expression analysis of mouse tumors revealed a variety of substantial changes at the tumor site following radiation. Genes associated with antigen presentation, infiltration of immune cells, adhesion, and activation of the innate immune system were upregulated. A combination of radiation and immunotherapy induced significant downregulation of tumor associated factors and upregulation of tumor suppressors. Moreover, combination therapy significantly increased CD4 + , CD8 + and NKT cell infiltration of mouse tumors. Our data provide a scientific rationale for combining immunotherapy with radiation and provide a basis for the development of more potent anti-cancer therapies. The online version of this article (doi:10.1186/1748-717X-9-180) contains supplementary material, which is available to authorized users

  17. UOP HRM 531 Entire Course NEW

    OpenAIRE

    ADMIN

    2018-01-01

    UOP HRM 531 Entire Course NEW Check this A+ tutorial guideline at http://www.hrm531assignment.com/hrm-531-uop/hrm-531-entire-course -latest For more classes visit http://www.hrm531assignment.com HRM 531 Week 1 Employment Law Report (2 Papers) HRM 531 Week 2 Change Management Impact (2 Papers) HRM 531 Week 3 Individual Compensation and Benefits Strategy (2 Papers) HRM 531 Week 3 Team Salary Inequities Case Study AstraZeneca (2 Papers) HRM 531 W...

  18. Entire cyclic cohomology and modular theory

    International Nuclear Information System (INIS)

    Stoytchev, O.Ts.

    1992-04-01

    We display a close relationship between C* and W*-dynamical systems with KMS states on them and entire cyclic cohomology theory. We construct a character form which assigns to each such system (A, α, R) an even entire cyclic cocycle of the subalgebra A of differentiable (with respect to the given automorphism group) elements of A. We argue that the most interesting case is the von Neumann algebra one, where the automorphism group is determined uniquely by the faithful normal state on the algebra (the modular group) and where the character may provide important information about the algebra. (author). 11 refs

  19. A Genomics-Based Classification of Human Lung Tumors

    NARCIS (Netherlands)

    Seidel, Danila; Zander, Thomas; Heukamp, Lukas C.; Peifer, Martin; Bos, Marc; Fernandez-Cuesta, Lynnette; Leenders, Frauke; Lu, Xin; Ansen, Sascha; Gardizi, Masyar; Nguyen, Chau; Berg, Johannes; Russell, Prudence; Wainer, Zoe; Schildhaus, Hans-Ulrich; Rogers, Toni-Maree; Solomon, Benjamin; Pao, William; Carter, Scott L.; Getz, Gad; Hayes, D. Neil; Wilkerson, Matthew D.; Thunnissen, Erik; Travis, William D.; Perner, Sven; Wright, Gavin; Brambilla, Elisabeth; Buettner, Reinhard; Wolf, Juergen; Thomas, Roman; Gabler, Franziska; Wilkening, Ines; Mueller, Christian; Dahmen, Ilona; Menon, Roopika; Koenig, Katharina; Albus, Kerstin; Merkelbach-Bruse, Sabine; Fassunke, Jana; Schmitz, Katja; Kuenstlinger, Helen; Kleine, Michaela; Binot, Elke; Querings, Silvia; Altmueller, Janine; Boessmann, Ingelore; Nuemberg, Peter; Schneider, Peter; Groen, Harry; Timens, Wim

    2013-01-01

    We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic

  20. Central nervous system tumors: a hospital based analysis

    International Nuclear Information System (INIS)

    Ayaz, B.; Lodhi, F.; Hasan, M.

    2011-01-01

    Objective: To assess the spectrum of CNS tumors and provide benchmark data for future studies assessing data in continuum. Patients and Methods: One hundred cases fulfilling the inclusion criteria were included between the ages of 1-85 years belonging to both genders. Results: Majority of the cases were seen in the year 2008 with the most commonly encountered lesion being the glial tumors followed by the meningiothelial neoplasms. Our findings were similar to previous similar studies in our setup with little change in trends. Conclusion: Glial tumors appear to be more common in our setup whereas the popularly believed Meningiothelial tumors though common came next. Our study can form the benchmark data upon which future studies can be conducted. (author)

  1. Development of Antibody-Based Vaccines Targeting the Tumor Vasculature.

    Science.gov (United States)

    Zhuang, Xiaodong; Bicknell, Roy

    2016-01-01

    A functional vasculature is essential for tumor progression and malignant cell metastasis. Endothelial cells lining blood vessels in the tumor are exposed to a unique microenvironment, which in turn induces expression of specific proteins designated as tumor endothelial markers (TEMs). TEMs either localized at the plasma membrane or secreted into the extracellular matrix are accessible for antibody targeting, which can be either infused or generated de novo via vaccination. Recent studies have demonstrated vaccines against several TEMs can induce a strong antibody response accompanied by a potent antitumor effect in animal models. These findings present an exciting field for novel anticancer therapy development. As most of the TEMs are self-antigens, breaking tolerance is necessary for a successful vaccine. This chapter describes approaches to efficiently induce a robust antibody response against the tumor vasculature.

  2. Brainstem tolerance to conformal radiotherapy of skull base tumors

    International Nuclear Information System (INIS)

    Debus, J.; Hug, E.B.; Liebsch, N.J.; O'Farrel, D.; Finkelstein, D.; Efird, J.; Munzenrider, J.E.

    1997-01-01

    Purpose: The aim of this study was to analyze the long-term incidence of brainstem toxicity in patients treated for skull base tumors with high dose conformal radiotherapy. Methods and Materials: Between 1974 and 1995, 367 patients with chordomas (n = 195) and chondrosarcomas (n = 172) of the base of skull have been treated with combined megavoltage photon and 160 MeV proton radiotherapy. Following 3D treatment planning with delineation of target volumes and critical nontarget structures dose distributions and dose-volume histograms were calculated. Radiotherapy was given an 1.8 Gy or CGE (=Cobalt Gray Equivalent) dose per fraction, with prescribed target doses ranging from 63 CGE to 79.2 CGE (mean = 67.8 CGE). Doses to the brainstem surface were limited to ≤64 CGE and to the brainstem center to ≤53 CGE. Results: Follow-up time ranged from 6 months to 21.4 years (mean = 42.5 months). Brainstem toxicity was observed in 17 of 367 patients attributable to treatment, resulting in death of three patients. Actuarial rates of 5 and 10-year high-grade toxicity-free survival were 94 and 88%, respectively. Increased risk of brainstem toxicity was significantly associated with maximum dose to brainstem, volume of brainstem receiving ≥50 CGE, ≥55 CGE, and ≥60 CGE, number of surgical procedures, and prevalence of diabetes or high blood pressure. Multivariate analysis identified three independent factors as important prognosticators: number of surgical procedures (p < 0.001), volume of the brainstem receiving 60 CGE (p < 0.001), and prevalence of diabetes (p < 0.01). Conclusions: Tolerance of brainstem to fractionated radiotherapy appears to be a steep function of tissue volume included in high dose regions rather than the maximum dose of brainstem alone. In addition, presence of predisposing factors as well as extent of surgical manipulation can significantly lower brainstem tolerance in the individual patient

  3. The Teichmuller Space of an Entire Function

    DEFF Research Database (Denmark)

    Fagella, Nuria; Henriksen, Christian

    2008-01-01

    points of any quasiconformal automorphism that commutes with f and which is homotopic to the identity, rel. the ideal boundary of the domain. As a consequence, the general framework of McMullen and Sullivan [McMS98] for rational functions applies also to entire functions and we can apply it to study...

  4. AFM image of an entire polygene chromosome

    International Nuclear Information System (INIS)

    Li Minqian; Takeuchi; Ikai, A.

    1994-01-01

    The author present AFM images of an entire polygene chromosome of Drosophila for the first time. Comparing with conventional optical microscope, the AFM image of the polygene chromosomes provides much higher resolution and 3-D measurement capability which will lead to finer scale gene mapping and identification

  5. A voxel-based multiscale model to simulate the radiation response of hypoxic tumors.

    Science.gov (United States)

    Espinoza, I; Peschke, P; Karger, C P

    2015-01-01

    In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan. A voxel-based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation-induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions. The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the model, tumor shrinkage was

  6. A voxel-based multiscale model to simulate the radiation response of hypoxic tumors

    International Nuclear Information System (INIS)

    Espinoza, I.; Peschke, P.; Karger, C. P.

    2015-01-01

    Purpose: In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan. Methods: A voxel-based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation-induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions. Results: The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the

  7. Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

    Science.gov (United States)

    de Paula Silva, Neimar; de Souza Reis, Rejane; Garcia Cunha, Rafael; Pinto Oliveira, Júlio Fernando; Santos, Marceli de Oliveira; Pombo-de-Oliveira, Maria S; de Camargo, Beatriz

    2016-01-01

    Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics. A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS) or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma). Children aged birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS) was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01)). Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma. This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

  8. Trend analysis of mortality rates and causes of death in children under 5 years old in Beijing, China from 1992 to 2015 and forecast of mortality into the future: an entire population-based epidemiological study.

    Science.gov (United States)

    Cao, Han; Wang, Jing; Li, Yichen; Li, Dongyang; Guo, Jin; Hu, Yifei; Meng, Kai; He, Dian; Liu, Bin; Liu, Zheng; Qi, Han; Zhang, Ling

    2017-09-18

    To analyse trends in mortality and causes of death among children aged under 5 years in Beijing, China between 1992 and 2015 and to forecast under-5 mortality rates (U5MRs) for the period 2016-2020. An entire population-based epidemiological study was conducted. Data collection was based on the Child Death Reporting Card of the Beijing Under-5 Mortality Rate Surveillance Network. Trends in mortality and leading causes of death were analysed using the χ 2 test and SPSS 19.0 software. An autoregressive integrated moving average (ARIMA) model was fitted to forecast U5MRs between 2016 and 2020 using the EViews 8.0 software. Mortality in neonates, infants and children aged under 5 years decreased by 84.06%, 80.04% and 80.17% from 1992 to 2015, respectively. However, the U5MR increased by 7.20% from 2013 to 2015. Birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities comprised the top five causes of death. The greatest, most rapid reduction was that of pneumonia by 92.26%, with an annual average rate of reduction of 10.53%. The distribution of causes of death differed among children of different ages. Accidental asphyxia and sepsis were among the top five causes of death in children aged 28 days to 1 year and accident was among the top five causes in children aged 1-4 years. The U5MRs in Beijing are projected to be 2.88‰, 2.87‰, 2.90‰, 2.97‰ and 3.09‰ for the period 2016-2020, based on the predictive model. Beijing has made considerable progress in reducing U5MRs from 1992 to 2015. However, U5MRs could show a slight upward trend from 2016 to 2020. Future considerations for child healthcare include the management of birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities. Specific preventative measures should be implemented for children of various age groups. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All

  9. Lateral skull base approaches in the management of benign parapharyngeal space tumors.

    Science.gov (United States)

    Prasad, Sampath Chandra; Piccirillo, Enrico; Chovanec, Martin; La Melia, Claudio; De Donato, Giuseppe; Sanna, Mario

    2015-06-01

    To evaluate the role of lateral skull base approaches in the management of benign parapharyngeal space tumors and to propose an algorithm for their surgical approach. Retrospective study of patients with benign parapharyngeal space tumors. The clinical features, radiology and preoperative management of skull base neurovasculature, the surgical approaches and overall results were recorded. 46 patients presented with 48 tumors. 12 were prestyloid and 36 poststyloid. 19 (39.6%) tumors were paragangliomas, 15 (31.25%) were schwannomas and 11 (23%) were pleomorphic adenomas. Preoperative embolization was performed in 19, stenting of the internal carotid artery in 4 and permanent balloon occlusion in 2 patients. 19 tumors were approached by the transcervical, 13 by transcervical-transparotid, 5 by transcervical-transmastoid, 6, 1 and 2 tumors by the infratemporal fossa approach types A, B and D, respectively. Total radical tumor removal was achieved in 46 (96%) of the cases. Lateral skull base approaches have an advantage over other approaches in the management of benign tumors of the parapharyngeal space due to the fact that they provide excellent exposure with less morbidity. The use of microscope combined with bipolar cautery reduces morbidity. Stenting of internal carotid artery gives a chance for complete tumor removal with arterial preservation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

    International Nuclear Information System (INIS)

    Malinowski, Kathleen T.; McAvoy, Thomas J.; George, Rohini; Dieterich, Sonja; D'Souza, Warren D.

    2012-01-01

    Purpose: To investigate the effect of tumor site, measurement precision, tumor–surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor–surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor–surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3–3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

  11. Mitigation of motion artifacts in CBCT of lung tumors based on tracked tumor motion during CBCT acquisition

    International Nuclear Information System (INIS)

    Lewis, John H; Li Ruijiang; Jia Xun; Watkins, W Tyler; Song, William Y; Jiang, Steve B; Lou, Yifei

    2011-01-01

    An algorithm capable of mitigating respiratory motion blurring artifacts in cone-beam computed tomography (CBCT) lung tumor images based on the motion of the tumor during the CBCT scan is developed. The tumor motion trajectory and probability density function (PDF) are reconstructed from the acquired CBCT projection images using a recently developed algorithm Lewis et al (2010 Phys. Med. Biol. 55 2505-22). Assuming that the effects of motion blurring can be represented by convolution of the static lung (or tumor) anatomy with the motion PDF, a cost function is defined, consisting of a data fidelity term and a total variation regularization term. Deconvolution is performed through iterative minimization of this cost function. The algorithm was tested on digital respiratory phantom, physical respiratory phantom and patient data. A clear qualitative improvement is evident in the deblurred images as compared to the motion-blurred images for all cases. Line profiles show that the tumor boundaries are more accurately and clearly represented in the deblurred images. The normalized root-mean-squared error between the images used as ground truth and the motion-blurred images are 0.29, 0.12 and 0.30 in the digital phantom, physical phantom and patient data, respectively. Deblurring reduces the corresponding values to 0.13, 0.07 and 0.19. Application of a -700 HU threshold to the digital phantom results in tumor dimension measurements along the superior-inferior axis of 2.8, 1.8 and 1.9 cm in the motion-blurred, ground truth and deblurred images, respectively. Corresponding values for the physical phantom are 3.4, 2.7 and 2.7 cm. A threshold of -500 HU applied to the patient case gives measurements of 3.1, 1.6 and 1.7 cm along the SI axis in the CBCT, 4DCT and deblurred images, respectively. This technique could provide more accurate information about a lung tumor's size and shape on the day of treatment.

  12. Mathematical Based Calculation of Drug Penetration Depth in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2016-01-01

    Full Text Available Cancer is a class of diseases characterized by out-of-control cells’ growth which affect cells and make them damaged. Many treatment options for cancer exist. Chemotherapy as an important treatment option is the use of drugs to treat cancer. The anticancer drug travels to the tumor and then diffuses in it through capillaries. The diffusion of drugs in the solid tumor is limited by penetration depth which is different in case of different drugs and cancers. The computation of this depth is important as it helps physicians to investigate about treatment of infected tissue. Although many efforts have been made on studying and measuring drug penetration depth, less works have been done on computing this length from a mathematical point of view. In this paper, first we propose phase lagging model for diffusion of drug in the tumor. Then, using this model on one side and considering the classic diffusion on the other side, we compute the drug penetration depth in the solid tumor. This computed value of drug penetration depth is corroborated by comparison with the values measured by experiments.

  13. STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT

    Science.gov (United States)

    Brown, Wade H.; Pearce, Louise

    1923-01-01

    Data bearing on the occurrence and distribution of metastases, as recorded in the preceding papers of the series, are analyzed with reference to the parts played by the tumor cell and by conditions which influence cell distribution and cell growth. It is shown that, while the tumor cell is an essential element in the production of metastases, its influence is relatively constant, and that the prime factors responsible for variations in the occurrence and distribution of metastatic growths are conditions that influence cell distribution or that affect the viability of the cell during transport, and conditions that affect the nutrition of the cell wherever it may become lodged. It is further shown that both the presence and the absence of metastases, as well as peculiarities of distribution and of growth, are susceptible of a comparatively simple explanation upon the basis of well recognized principles of pathological action. In brief, it was found that, while the tumor cells might be distributed by either the blood stream or the lymphatics, the mode of distribution and the fate of the cells were determined in accordance with the same general principles that are applicable to the distribution and disposal of foreign cells introduced into the animal body. It was pointed out, however, that in applying these principles to tumor metastasis, it was necessary to recognize the fact that tumor cells bear a definite relation to the tissues of the host and that they are living and agressive agents. Hence, the reaction that they arouse differs in some respects from that produced by inert or unorganized foreign material or by living cells of a foreign species. PMID:19868797

  14. Preoperative Visualization of Cranial Nerves in Skull Base Tumor Surgery Using Diffusion Tensor Imaging Technology.

    Science.gov (United States)

    Ma, Jun; Su, Shaobo; Yue, Shuyuan; Zhao, Yan; Li, Yonggang; Chen, Xiaochen; Ma, Hui

    2016-01-01

    To visualize cranial nerves (CNs) using diffusion tensor imaging (DTI) with special parameters. This study also involved the evaluation of preoperative estimates and intraoperative confirmation of the relationship between nerves and tumor by verifying the accuracy of visualization. 3T magnetic resonance imaging scans including 3D-FSPGR, FIESTA, and DTI were used to collect information from 18 patients with skull base tumor. DTI data were integrated into the 3D slicer for fiber tracking and overlapped anatomic images to determine course of nerves. 3D reconstruction of tumors was achieved to perform neighboring, encasing, and invading relationship between lesion and nerves. Optic pathway including the optic chiasm could be traced in cases of tuberculum sellae meningioma and hypophysoma (pituitary tumor). The oculomotor nerve, from the interpeduncular fossa out of the brain stem to supraorbital fissure, was clearly visible in parasellar meningioma cases. Meanwhile, cisternal parts of trigeminal nerve and abducens nerve, facial nerve were also imaged well in vestibular schwannomas and petroclival meningioma cases. The 3D-spatial relationship between CNs and skull base tumor estimated preoperatively by tumor modeling and tractography corresponded to the results determined during surgery. Supported by DTI and 3D slicer, preoperative 3D reconstruction of most CNs related to skull base tumor is feasible in pathological circumstances. We consider DTI Technology to be a useful tool for predicting the course and location of most CNs, and syntopy between them and skull base tumor.

  15. The results of gamma knife radiosurgery for malignant skull base tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takayuki; Kobayashi, Tatsuya; Kida, Yoshihisa; Oyama, Hirofumi; Niwa, Masahiro [Komaki City Hospital, Aichi (Japan)

    1996-03-01

    The results of gamma knife radiosurgery for malignant skull base tumors were analyzed using repeated magnetic resonance imagings and neurological examinations. Nineteen malignant skull base tumors were treated and followed up for 22.3 months (5-40 months) using MR imagings. The mean age was 54.4 years old (ranging from 16-85). Ten were male and 9 were female. Prior to the radiosurgery, removal of the tumors in 17 cases, conventional radiation therapy in 7, and chemotherapy in 4 etc. were performed. The pathological diagnoses were chordoma in 6 patients, metastatic tumors in 5, epipharyngeal carcinoma in 2, adenoid cystic carcinoma in 2, and others in 4. The locations of tumors were clivus in 8, parasellar region in 5, epipharynx in 2, paranasal sinus in 2, C-P angle in 1, and intraorbital region in 1 (14 intracranial and 5 extracranial). The mean diameter of the tumor was 33.5 mm. The mean maximum dose was 26.8 Gy and the mean marginal dose was 12.9 Gy during treatment. Repeated MR imagings revealed decrease of tumor size in 12 cases, showing no change in 1, and increase of tumor size in 5 (unknown in 1). Follow-up neurological examinations showed improvement in 3 patients, no change in 9, and deterioration in 7. There were 11 deaths during a mean follow-up period of 17.8 months (5-32 months) and another 8 cases are alive for a mean follow-up of 30.5 months (20-40 months) after the radiosurgery. Although the tumor size was large at the time of treatment, the results of gamma knife radiosurgery were promising. Considering the quality of life of patients with malignant skull base tumors, it is emphasized that gamma knife treatment is the method of choice compared with radical removal of the tumors. (author).

  16. Ultrasound-based tumor movement compensation during navigated laparoscopic liver interventions.

    Science.gov (United States)

    Shahin, Osama; Beširević, Armin; Kleemann, Markus; Schlaefer, Alexander

    2014-05-01

    Image-guided navigation aims to provide better orientation and accuracy in laparoscopic interventions. However, the ability of the navigation system to reflect anatomical changes and maintain high accuracy during the procedure is crucial. This is particularly challenging in soft organs such as the liver, where surgical manipulation causes significant tumor movements. We propose a fast approach to obtain an accurate estimation of the tumor position throughout the procedure. Initially, a three-dimensional (3D) ultrasound image is reconstructed and the tumor is segmented. During surgery, the position of the tumor is updated based on newly acquired tracked ultrasound images. The initial segmentation of the tumor is used to automatically detect the tumor and update its position in the navigation system. Two experiments were conducted. First, a controlled phantom motion using a robot was performed to validate the tracking accuracy. Second, a needle navigation scenario based on pseudotumors injected into ex vivo porcine liver was studied. In the robot-based evaluation, the approach estimated the target location with an accuracy of 0.4 ± 0.3 mm. The mean navigation error in the needle experiment was 1.2 ± 0.6 mm, and the algorithm compensated for tumor shifts up to 38 mm in an average time of 1 s. We demonstrated a navigation approach based on tracked laparoscopic ultrasound (LUS), and focused on the neighborhood of the tumor. Our experimental results indicate that this approach can be used to quickly and accurately compensate for tumor movements caused by surgical manipulation during laparoscopic interventions. The proposed approach has the advantage of being based on the routinely used LUS; however, it upgrades its functionality to estimate the tumor position in 3D. Hence, the approach is repeatable throughout surgery, and enables high navigation accuracy to be maintained.

  17. A D-D/D-T fusion reaction based neutron generator system for liver tumor BNCT

    International Nuclear Information System (INIS)

    Koivunoro, H.; Lou, T.P.; Leung, K. N.; Reijonen, J.

    2003-01-01

    Boron-neutron capture therapy (BNCT) is an experimental radiation treatment modality used for highly malignant tumor treatments. Prior to irradiation with low energetic neutrons, a 10B compound is located selectively in the tumor cells. The effect of the treatment is based on the high LET radiation released in the 10 B(n,α) 7 Li reaction with thermal neutrons. BNCT has been used experimentally for brain tumor and melanoma treatments. Lately applications of other severe tumor type treatments have been introduced. Results have shown that liver tumors can also be treated by BNCT. At Lawrence Berkeley National Laboratory, various compact neutron generators based on D-D or D-T fusion reactions are being developed. The earlier theoretical studies of the D-D or D-T fusion reaction based neutron generators have shown that the optimal moderator and reflector configuration for brain tumor BNCT can be created. In this work, the applicability of 2.5 MeV neutrons for liver tumor BNCT application was studied. The optimal neutron energy for external liver treatments is not known. Neutron beams of different energies (1eV < E < 100 keV) were simulated and the dose distribution in the liver was calculated with the MCNP simulation code. In order to obtain the optimal neutron energy spectrum with the D-D neutrons, various moderator designs were performed using MCNP simulations. In this article the neutron spectrum and the optimized beam shaping assembly for liver tumor treatments is presented

  18. Circulating Tumor Cells: From Theory to Nanotechnology-Based Detection

    Science.gov (United States)

    Ming, Yue; Li, Yuanyuan; Xing, Haiyan; Luo, Minghe; Li, Ziwei; Chen, Jianhong; Mo, Jingxin; Shi, Sanjun

    2017-01-01

    Cancer stem cells with stem-cell properties are regarded as tumor initiating cells. Sharing stem-cell properties, circulating tumor cells (CTCs) are responsible for the development of metastasis, which significant affects CTC analysis in clinical practice. Due to their extremely low occurrence in blood, however, it is challenging to enumerate and analyze CTCs. Nanotechnology is able to address the problems of insufficient capture efficiency and low purity of CTCs owing to the unique structural and functional properties of nanomaterials, showing strong promise for CTC isolation and detection. In this review, we discuss the role of stem-like CTCs in metastases, provide insight into recent progress in CTC isolation and detection approaches using various nanoplatforms, and highlight the role of nanotechnology in the advancement of CTC research. PMID:28203204

  19. Teaching Discrete Mathematics Entirely from Primary Historical Sources

    Science.gov (United States)

    Barnett, Janet Heine; Bezhanishvili, Guram; Lodder, Jerry; Pengelley, David

    2016-01-01

    We describe teaching an introductory discrete mathematics course entirely from student projects based on primary historical sources. We present case studies of four projects that cover the content of a one-semester course, and mention various other courses that we have taught with primary source projects.

  20. Entirely saturated unilateral smear of laser spot in CCD

    International Nuclear Information System (INIS)

    Zhang Zhen; Zhou Menglian; Zhang Jianmin; Lin Xinwei

    2013-01-01

    In the video of linear CCD camera being irradiated by 532 nm CW laser, the entirely saturated unilateral smear of laser spot was found. The smear area does not represent the distribution of laser. Since this smear lies merely in one side of laser spot, it can not be induced by light leaking or carriers blooming, and it may be induced by charge transfer loss. However, the feature that the smear area is entirely saturated can not be explained by the current constant model of charge transfer inefficiency. Based on the inner structure and operating principle of buried channel CCD, a new model of charge transfer inefficiency that varies with charge quantity is proposed, which can explain the entirely saturated unilateral smear of laser spot. (authors)

  1. Automated lung tumor segmentation for whole body PET volume based on novel downhill region growing

    Science.gov (United States)

    Ballangan, Cherry; Wang, Xiuying; Eberl, Stefan; Fulham, Michael; Feng, Dagan

    2010-03-01

    We propose an automated lung tumor segmentation method for whole body PET images based on a novel downhill region growing (DRG) technique, which regards homogeneous tumor hotspots as 3D monotonically decreasing functions. The method has three major steps: thoracic slice extraction with K-means clustering of the slice features; hotspot segmentation with DRG; and decision tree analysis based hotspot classification. To overcome the common problem of leakage into adjacent hotspots in automated lung tumor segmentation, DRG employs the tumors' SUV monotonicity features. DRG also uses gradient magnitude of tumors' SUV to improve tumor boundary definition. We used 14 PET volumes from patients with primary NSCLC for validation. The thoracic region extraction step achieved good and consistent results for all patients despite marked differences in size and shape of the lungs and the presence of large tumors. The DRG technique was able to avoid the problem of leakage into adjacent hotspots and produced a volumetric overlap fraction of 0.61 +/- 0.13 which outperformed four other methods where the overlap fraction varied from 0.40 +/- 0.24 to 0.59 +/- 0.14. Of the 18 tumors in 14 NSCLC studies, 15 lesions were classified correctly, 2 were false negative and 15 were false positive.

  2. Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.

    Science.gov (United States)

    Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan

    2016-04-01

    With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. © The Author 2015. Published by Oxford University Press.

  3. Improving the accuracy of brain tumor surgery via Raman-based technology.

    Science.gov (United States)

    Hollon, Todd; Lewis, Spencer; Freudiger, Christian W; Sunney Xie, X; Orringer, Daniel A

    2016-03-01

    Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H & E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors.

  4. Temporalis Myofascial Flap for Primary Cranial Base Reconstruction after Tumor Resection

    OpenAIRE

    Eldaly, Ahmed; Magdy, Emad A.; Nour, Yasser A.; Gaafar, Alaa H.

    2008-01-01

    Objective: To evaluate the use of the temporalis myofascial flap in primary cranial base reconstruction following surgical tumor ablation and to explain technical issues, potential complications, and donor site consequences along with their management. Design: Retrospective case series. Setting: Tertiary referral center. Participants: Forty-one consecutive patients receiving primary temporalis myofascial flap reconstructions following cranial base tumor resections in a 4-year period. Main Out...

  5. Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

    Directory of Open Access Journals (Sweden)

    Neimar de Paula Silva

    Full Text Available Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics.A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma. Children aged <6 years were selected. Adjustments were made for potential confounders. Odds ratios (OR with 95% confidence intervals (CI were computed by unconditional logistic regression analysis using SPSS.Males, high maternal education level, and birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01. Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma.This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

  6. Pancreatic tumor detection using hypericin-based fluorescence spectroscopy and cytology

    Science.gov (United States)

    Lavu, Harish; Geary, Kevin; Fetterman, Harold R.; Saxton, Romaine E.

    2005-04-01

    Hypericin is a novel, highly fluorescent photosensitizer that exhibits selective tumor cell uptake properties and is particularly resistant to photobleaching. In this study, we have characterized hypericin uptake in human pancreatic tumor cells with relation to incubation time, cell number, and drug concentration. Ex vivo hypericin based fluorescence spectroscopy was performed to detect the presence of MIA PaCa-2 pancreatic tumor cells in the peritoneal cavity of BALB/c nude mice, as well as to quantify gross tumor burden. Hypericin based cytology of peritoneal lavage samples, using both one and two photon laser confocal microscopy, demonstrated more than a two-fold increase in fluorescence emission of pancreatic tumor cells as compared to control samples. In vitro treatment of pancreatic cancer cells with hypericin based photodynamic therapy showed tumor cell cytotoxicity in a drug dose, incident laser power, and time dependent manner. For these experiments, a continuous wavelength solid-state laser source (532 nm) was operated at power levels in the range of 100-400 mW. Potential applications of hypericin in tumor diagnosis, staging, and therapy will be presented.

  7. Photoacoustic imaging to assess pixel-based sO2 distributions in experimental prostate tumors.

    Science.gov (United States)

    Bendinger, Alina L; Glowa, Christin; Peter, Jörg; Karger, Christian P

    2018-03-01

    A protocol for photoacoustic imaging (PAI) has been developed to assess pixel-based oxygen saturation (sO2) distributions of experimental tumor models. The protocol was applied to evaluate the dependence of PAI results on measurement settings, reproducibility of PAI, and for the characterization of the oxygenation status of experimental prostate tumor sublines (Dunning R3327-H, -HI, -AT1) implanted subcutaneously in male Copenhagen rats. The three-dimensional (3-D) PA data employing two wavelengths were used to estimate sO2 distributions. If the PA signal was sufficiently strong, the distributions were independent from signal gain, threshold, and positioning of animals. Reproducibility of sO2 distributions with respect to shape and median values was demonstrated over several days. The three tumor sublines were characterized by the shapes of their sO2 distributions and their temporal response after external changes of the oxygen supply (100% O2 or air breathing and clamping of tumor-supplying artery). The established protocol showed to be suitable for detecting temporal changes in tumor oxygenation as well as differences in oxygenation between tumor sublines. PA results were in accordance with histology for hypoxia, perfusion, and vasculature. The presented protocol for the assessment of pixel-based sO2 distributions provides more detailed information as compared to conventional region-of-interest-based analysis of PAI, especially with respect to the detection of temporal changes and tumor heterogeneity. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  8. Photoacoustic imaging to assess pixel-based sO2 distributions in experimental prostate tumors

    Science.gov (United States)

    Bendinger, Alina L.; Glowa, Christin; Peter, Jörg; Karger, Christian P.

    2018-03-01

    A protocol for photoacoustic imaging (PAI) has been developed to assess pixel-based oxygen saturation (sO2) distributions of experimental tumor models. The protocol was applied to evaluate the dependence of PAI results on measurement settings, reproducibility of PAI, and for the characterization of the oxygenation status of experimental prostate tumor sublines (Dunning R3327-H, -HI, -AT1) implanted subcutaneously in male Copenhagen rats. The three-dimensional (3-D) PA data employing two wavelengths were used to estimate sO2 distributions. If the PA signal was sufficiently strong, the distributions were independent from signal gain, threshold, and positioning of animals. Reproducibility of sO2 distributions with respect to shape and median values was demonstrated over several days. The three tumor sublines were characterized by the shapes of their sO2 distributions and their temporal response after external changes of the oxygen supply (100% O2 or air breathing and clamping of tumor-supplying artery). The established protocol showed to be suitable for detecting temporal changes in tumor oxygenation as well as differences in oxygenation between tumor sublines. PA results were in accordance with histology for hypoxia, perfusion, and vasculature. The presented protocol for the assessment of pixel-based sO2 distributions provides more detailed information as compared to conventional region-of-interest-based analysis of PAI, especially with respect to the detection of temporal changes and tumor heterogeneity.

  9. Iterative volume morphing and learning for mobile tumor based on 4DCT.

    Science.gov (United States)

    Mao, Songan; Wu, Huanmei; Sandison, George; Fang, Shiaofen

    2017-02-21

    During image-guided cancer radiation treatment, three-dimensional (3D) tumor volumetric information is important for treatment success. However, it is typically not feasible to image a patient's 3D tumor continuously in real time during treatment due to concern over excessive patient radiation dose. We present a new iterative morphing algorithm to predict the real-time 3D tumor volume based on time-resolved computed tomography (4DCT) acquired before treatment. An offline iterative learning process has been designed to derive a target volumetric deformation function from one breathing phase to another. Real-time volumetric prediction is performed to derive the target 3D volume during treatment delivery. The proposed iterative deformable approach for tumor volume morphing and prediction based on 4DCT is innovative because it makes three major contributions: (1) a novel approach to landmark selection on 3D tumor surfaces using a minimum bounding box; (2) an iterative morphing algorithm to generate the 3D tumor volume using mapped landmarks; and (3) an online tumor volume prediction strategy based on previously trained deformation functions utilizing 4DCT. The experimental performance showed that the maximum morphing deviations are 0.27% and 1.25% for original patient data and artificially generated data, which is promising. This newly developed algorithm and implementation will have important applications for treatment planning, dose calculation and treatment validation in cancer radiation treatment.

  10. A survey of MRI-based medical image analysis for brain tumor studies

    Science.gov (United States)

    Bauer, Stefan; Wiest, Roland; Nolte, Lutz-P.; Reyes, Mauricio

    2013-07-01

    MRI-based medical image analysis for brain tumor studies is gaining attention in recent times due to an increased need for efficient and objective evaluation of large amounts of data. While the pioneering approaches applying automated methods for the analysis of brain tumor images date back almost two decades, the current methods are becoming more mature and coming closer to routine clinical application. This review aims to provide a comprehensive overview by giving a brief introduction to brain tumors and imaging of brain tumors first. Then, we review the state of the art in segmentation, registration and modeling related to tumor-bearing brain images with a focus on gliomas. The objective in the segmentation is outlining the tumor including its sub-compartments and surrounding tissues, while the main challenge in registration and modeling is the handling of morphological changes caused by the tumor. The qualities of different approaches are discussed with a focus on methods that can be applied on standard clinical imaging protocols. Finally, a critical assessment of the current state is performed and future developments and trends are addressed, giving special attention to recent developments in radiological tumor assessment guidelines.

  11. A survey of MRI-based medical image analysis for brain tumor studies

    International Nuclear Information System (INIS)

    Bauer, Stefan; Nolte, Lutz-P; Reyes, Mauricio; Wiest, Roland

    2013-01-01

    MRI-based medical image analysis for brain tumor studies is gaining attention in recent times due to an increased need for efficient and objective evaluation of large amounts of data. While the pioneering approaches applying automated methods for the analysis of brain tumor images date back almost two decades, the current methods are becoming more mature and coming closer to routine clinical application. This review aims to provide a comprehensive overview by giving a brief introduction to brain tumors and imaging of brain tumors first. Then, we review the state of the art in segmentation, registration and modeling related to tumor-bearing brain images with a focus on gliomas. The objective in the segmentation is outlining the tumor including its sub-compartments and surrounding tissues, while the main challenge in registration and modeling is the handling of morphological changes caused by the tumor. The qualities of different approaches are discussed with a focus on methods that can be applied on standard clinical imaging protocols. Finally, a critical assessment of the current state is performed and future developments and trends are addressed, giving special attention to recent developments in radiological tumor assessment guidelines. (topical review)

  12. Biodistribution of ultra small gadolinium-based nanoparticles as theranostic agent: application to brain tumors.

    Science.gov (United States)

    Miladi, Imen; Duc, Géraldine Le; Kryza, David; Berniard, Aurélie; Mowat, Pierre; Roux, Stéphane; Taleb, Jacqueline; Bonazza, Pauline; Perriat, Pascal; Lux, François; Tillement, Olivier; Billotey, Claire; Janier, Marc

    2013-09-01

    Gadolinium-based nanoparticles are novel objects with interesting physical properties, allowing their use for diagnostic and therapeutic applications. Gadolinium-based nanoparticles were imaged following intravenous injection in healthy rats and rats grafted with 9L gliosarcoma tumors using magnetic resonance imaging and scintigraphic imaging. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles were rapidly cleared essentially by renal excretion. Accumulation of these nanoparticles in 9L gliosarcoma tumors implanted in the rat brain was quantitated. This passive and long-duration accumulation of gadolinium-based nanoparticles in tumor, which is related to disruption of the blood-brain barrier, is in good agreement with the use of these nanoparticles as radiosensitizers for brain tumors.

  13. Preoperative surgical planning and simulation of complex cranial base tumors in virtual reality

    Institute of Scientific and Technical Information of China (English)

    YI Zhi-qiang; LI Liang; MO Da-peng; ZHANG Jia-yong; ZHANG Yang; BAO Sheng-de

    2008-01-01

    @@ The extremely complex anatomic relationships among bone,tumor,blood vessels and cranial nerves remains a big challenge for cranial base tumor surgery.Therefore.a good understanding of the patient specific anatomy and a preoperative planning are helpful and crocial for the neurosurgeons.Three dimensional (3-D) visualization of various imaging techniques have been widely explored to enhance the comprehension of volumetric data for surgical planning.1 We used the Destroscope Virtual Reality (VR) System (Singapore,Volume Interaction Pte Ltd,software:RadioDexterTM 1.0) to optimize preoperative plan in the complex cranial base tumors.This system uses patient-specific,coregistered,fused radiology data sets that may be viewed stereoscopically and can be manipulated in a virtual reality environment.This article describes our experience with the Destroscope VR system in preoperative surgical planning and simulation for 5 patients with complex cranial base tumors and evaluates the clinical usefulness of this system.

  14. Precision cancer immunotherapy: optimizing dendritic cell-based strategies to induce tumor antigen-specific T-cell responses against individual patient tumors.

    Science.gov (United States)

    Osada, Takuya; Nagaoka, Koji; Takahara, Masashi; Yang, Xiao Yi; Liu, Cong-Xiao; Guo, Hongtao; Roy Choudhury, Kingshuk; Hobeika, Amy; Hartman, Zachary; Morse, Michael A; Lyerly, H Kim

    2015-05-01

    Most dendritic cell (DC)-based vaccines have loaded the DC with defined antigens, but loading with autologos tumor-derived antigens would generate DCs that activate personalized tumor-specific T-cell responses. We hypothesized that DC matured with an optimized combination of reagents and loaded with tumor-derived antigens using a clinically feasible electroporation strategy would induce potent antitumor immunity. We first studied the effects on DC maturation and antigen presentation of the addition of picibanil (OK432) to a combination of zoledronic acid, tumor necrosis factor-α, and prostaglandin E2. Using DC matured with the optimized combination, we tested 2 clinically feasible sources of autologous antigen for electroloading, total tumor mRNA or total tumor lysate, to determine which stimulated more potent antigen-specific T cells in vitro and activated more potent antitumor immunity in vivo. The combination of tumor necrosis factor-α/prostaglandin E2/zoledronic acid/OK432 generated DC with high expression of maturation markers and antigen-specific T-cell stimulatory function in vitro. Mature DC electroloaded with tumor-derived mRNA [mRNA electroporated dendritic cell (EPDC)] induced greater expansion of antigen-specific T cells in vitro than DC electroloaded with tumor lysate (lysate EPDC). In a therapeutic model of MC38-carcinoembryonic antigen colon cancer-bearing mice, vaccination with mRNA EPDC induced the most efficient anti-carcinoembryonic antigen cellular immune response, which significantly suppressed tumor growth. In conclusion, mature DC electroloaded with tumor-derived mRNA are a potent cancer vaccine, especially useful when specific tumor antigens for vaccination have not been identified, allowing autologous tumor, and if unavailable, allogeneic cell lines to be used as an unbiased source of antigen. Our data support clinical testing of this strategy.

  15. Brain tumor segmentation based on a hybrid clustering technique

    Directory of Open Access Journals (Sweden)

    Eman Abdel-Maksoud

    2015-03-01

    This paper presents an efficient image segmentation approach using K-means clustering technique integrated with Fuzzy C-means algorithm. It is followed by thresholding and level set segmentation stages to provide an accurate brain tumor detection. The proposed technique can get benefits of the K-means clustering for image segmentation in the aspects of minimal computation time. In addition, it can get advantages of the Fuzzy C-means in the aspects of accuracy. The performance of the proposed image segmentation approach was evaluated by comparing it with some state of the art segmentation algorithms in case of accuracy, processing time, and performance. The accuracy was evaluated by comparing the results with the ground truth of each processed image. The experimental results clarify the effectiveness of our proposed approach to deal with a higher number of segmentation problems via improving the segmentation quality and accuracy in minimal execution time.

  16. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    Science.gov (United States)

    Unkelbach, Jan; Menze, Bjoern H.; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A.

    2014-02-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  17. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    International Nuclear Information System (INIS)

    Unkelbach, Jan; Dittmann, Florian; Le, Matthieu; Shih, Helen A; Menze, Bjoern H; Ayache, Nicholas; Konukoglu, Ender

    2014-01-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher–Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  18. Nanobody-Based Delivery Systems for Diagnosis and Targeted Tumor Therapy

    Directory of Open Access Journals (Sweden)

    Yaozhong Hu

    2017-11-01

    Full Text Available The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma’s, monoclonal antibodies (mAbs have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue. By serendipity, a new kind of functional homodimeric antibody format was discovered in camelidae, known as heavy-chain antibodies (HCAbs. The cloning of the variable domain of HCAbs produces an attractive minimal-sized alternative for mAbs, referred to as VHH or nanobodies (Nbs. Apart from their dimensions in the single digit nanometer range, the unique characteristics of Nbs combine a high stability and solubility, low immunogenicity and excellent affinity and specificity against all possible targets including tumor markers. This stimulated the development of tumor-targeted therapeutic strategies. Some autonomous Nbs have been shown to act as antagonistic drugs, but more importantly, the targeting capacity of Nbs has been exploited to create drug delivery systems. Obviously, Nb-based targeted cancer therapy is mainly focused toward extracellular tumor markers, since the membrane barrier prevents antibodies to reach the most promising intracellular tumor markers. Potential strategies, such as lentiviral vectors and bacterial type 3 secretion system, are proposed to deliver target-specific Nbs into tumor cells and to block tumor markers intracellularly. Simultaneously, Nbs have also been employed for in vivo molecular imaging to diagnose diseased tissues and to monitor the treatment effects. Here, we review the state of the art and focus on recent developments with Nbs as

  19. Deep Learning and Texture-Based Semantic Label Fusion for Brain Tumor Segmentation.

    Science.gov (United States)

    Vidyaratne, L; Alam, M; Shboul, Z; Iftekharuddin, K M

    2018-01-01

    Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.

  20. Deep learning and texture-based semantic label fusion for brain tumor segmentation

    Science.gov (United States)

    Vidyaratne, L.; Alam, M.; Shboul, Z.; Iftekharuddin, K. M.

    2018-02-01

    Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.

  1. Partial least squares based gene expression analysis in estrogen receptor positive and negative breast tumors.

    Science.gov (United States)

    Ma, W; Zhang, T-F; Lu, P; Lu, S H

    2014-01-01

    Breast cancer is categorized into two broad groups: estrogen receptor positive (ER+) and ER negative (ER-) groups. Previous study proposed that under trastuzumab-based neoadjuvant chemotherapy, tumor initiating cell (TIC) featured ER- tumors response better than ER+ tumors. Exploration of the molecular difference of these two groups may help developing new therapeutic strategies, especially for ER- patients. With gene expression profile from the Gene Expression Omnibus (GEO) database, we performed partial least squares (PLS) based analysis, which is more sensitive than common variance/regression analysis. We acquired 512 differentially expressed genes. Four pathways were found to be enriched with differentially expressed genes, involving immune system, metabolism and genetic information processing process. Network analysis identified five hub genes with degrees higher than 10, including APP, ESR1, SMAD3, HDAC2, and PRKAA1. Our findings provide new understanding for the molecular difference between TIC featured ER- and ER+ breast tumors with the hope offer supports for therapeutic studies.

  2. Staging of gastroenteropancreatic neuroendocrine tumors: how we do it based on an evidence-based approach.

    LENUS (Irish Health Repository)

    McDermott, Shaunagh

    2013-01-01

    In contrast to other common types of malignant tumors, the vast majority of gastroenteropancreatic neuroendocrine tumors are well differentiated and slowly growing with only a minority showing aggressive behavior. It is important to accurately stage patients radiologically so the correct treatment can be implemented and to improve prognosis. In this article, we critically appraise the current literature in an effort to establish the current role of radiologic imaging in the staging of neuroendocrine tumors. We also discuss our protocol for staging neuroendocrine tumors.

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

    Science.gov (United States)

    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.

  4. Comparison of IGRT Registration Strategies for Optimal Coverage of Primary Lung Tumors and Involved Nodes Based on Multiple Four-Dimensional CT Scans Obtained Throughout the Radiotherapy Course

    International Nuclear Information System (INIS)

    Mohammed, Nasiruddin; Kestin, Larry; Grills, Inga; Shah, Chirag; Glide-Hurst, Carri; Yan, Di; Ionascu, Dan

    2012-01-01

    Purpose: To investigate the impact of primary tumor and involved lymph node (LN) geometry (centroid, shape, volume) on internal target volume (ITV) throughout treatment for locally advanced non–small cell lung cancer using weekly four-dimensional computed tomography (4DCT). Methods and Materials: Eleven patients with advanced non–small cell lung cancer were treated using image-guided radiotherapy with acquisition of weekly 10-Phase 4DCTs (n = 51). Initial ITV was based on planning 4DCT. Master-ITV incorporated target geometry across the entire treatment (all 4DCTs). Geographic miss was defined as the % Master-ITV positioned outside of the initial planning ITV after registration is complete. Registration strategies considered were bony (B), primary tumor soft tissue alone (T), and registration based on primary tumor and involved LNs (T L N). Results: The % geographic miss for the primary tumor, mediastinal, and hilar lymph nodes based on each registration strategy were (1) B: 30%, 30%, 30%; (2) T: 21%, 40%, 36%; and (3) T L N: 26%, 26%, 27%. Mean geographic expansions to encompass 100% of the primary tumor and involved LNs were 1.2 ± 0.7 cm and 0.8 ± 0.3 cm, respectively, for B and T L N. Primary and involved LN expansions were 0.7 ± 0.5 cm and 1.1 ± 0.5 cm for T. Conclusion: T is best for solitary targets. When treatments include primary tumor and LNs, B and T L N provide more comprehensive geographic coverage. We have identified high % geographic miss when considering multiple registration strategies. The dosimetric implications are the subject of future study.

  5. Comparison of IGRT Registration Strategies for Optimal Coverage of Primary Lung Tumors and Involved Nodes Based on Multiple Four-Dimensional CT Scans Obtained Throughout the Radiotherapy Course

    Energy Technology Data Exchange (ETDEWEB)

    Mohammed, Nasiruddin; Kestin, Larry; Grills, Inga; Shah, Chirag; Glide-Hurst, Carri; Yan, Di [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Ionascu, Dan, E-mail: Dan.ionascu@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)

    2012-03-15

    Purpose: To investigate the impact of primary tumor and involved lymph node (LN) geometry (centroid, shape, volume) on internal target volume (ITV) throughout treatment for locally advanced non-small cell lung cancer using weekly four-dimensional computed tomography (4DCT). Methods and Materials: Eleven patients with advanced non-small cell lung cancer were treated using image-guided radiotherapy with acquisition of weekly 10-Phase 4DCTs (n = 51). Initial ITV was based on planning 4DCT. Master-ITV incorporated target geometry across the entire treatment (all 4DCTs). Geographic miss was defined as the % Master-ITV positioned outside of the initial planning ITV after registration is complete. Registration strategies considered were bony (B), primary tumor soft tissue alone (T), and registration based on primary tumor and involved LNs (T{sub L}N). Results: The % geographic miss for the primary tumor, mediastinal, and hilar lymph nodes based on each registration strategy were (1) B: 30%, 30%, 30%; (2) T: 21%, 40%, 36%; and (3) T{sub L}N: 26%, 26%, 27%. Mean geographic expansions to encompass 100% of the primary tumor and involved LNs were 1.2 {+-} 0.7 cm and 0.8 {+-} 0.3 cm, respectively, for B and T{sub L}N. Primary and involved LN expansions were 0.7 {+-} 0.5 cm and 1.1 {+-} 0.5 cm for T. Conclusion: T is best for solitary targets. When treatments include primary tumor and LNs, B and T{sub L}N provide more comprehensive geographic coverage. We have identified high % geographic miss when considering multiple registration strategies. The dosimetric implications are the subject of future study.

  6. Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

    Science.gov (United States)

    Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

    1999-03-01

    We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

  7. Interrogation of metabolic and oxygen states of tumors with fiber-based luminescence lifetime spectroscopy.

    Science.gov (United States)

    Lukina, Maria; Orlova, Anna; Shirmanova, Marina; Shirokov, Daniil; Pavlikov, Anton; Neubauer, Antje; Studier, Hauke; Becker, Wolfgang; Zagaynova, Elena; Yoshihara, Toshitada; Tobita, Seiji; Shcheslavskiy, Vladislav

    2017-02-15

    The study of metabolic and oxygen states of cells in a tumor in vivo is crucial for understanding of the mechanisms responsible for tumor development and provides background for the relevant tumor's treatment. Here, we show that a specially designed implantable fiber-optic probe provides a promising tool for optical interrogation of metabolic and oxygen states of a tumor in vivo. In our experiments, the excitation light from a ps diode laser source is delivered to the sample through an exchangeable tip via a multimode fiber, and the emission light is transferred to the detector by another multimode fiber. Fluorescence lifetime of a nicotinamid adenine dinucleotide (NAD(P)H) and phosphorescence lifetime of an oxygen sensor based on an iridium (III) complex of enzothienylpyridine (BTPDM1) are explored both in model experiment in solutions and in living mice.

  8. Social Pedagogy for the Entire Lifespan

    DEFF Research Database (Denmark)

    The book proposes chapters on work with adults and older people, written by authors based in Belgium, Denmark, Norway, Poland, Spain, Sweden and Switzerland. The global dimension is covered by a chapter on the relationship between Latin American and European social pedagogy.......The book proposes chapters on work with adults and older people, written by authors based in Belgium, Denmark, Norway, Poland, Spain, Sweden and Switzerland. The global dimension is covered by a chapter on the relationship between Latin American and European social pedagogy....

  9. The role of stereotactic radiosurgery in the treatment of malignant skull base tumors

    International Nuclear Information System (INIS)

    Miller, Robert C.; Foote, Robert L.; Coffey, Robert J.; Gorman, Deborah A.; Earle, John D.; Schomberg, Paula J.; Kline, Robert W.

    1997-01-01

    Purpose: To determine the efficacy and toxicity of stereotactic radiosurgery in the treatment of malignant skull base tumors. Methods and Materials: Thirty-two patients with 35 newly diagnosed or recurrent malignant skull base tumors ≤33.5 cm 3 were treated using the Leksell Gamma unit. Tumor histologies included: adenoid cystic carcinoma, basal cell carcinoma, chondrosarcoma, chordoma, nasopharyngeal carcinoma, osteogenic sarcoma, and squamous cell carcinoma. Results: After a median follow-up of 2.3 years, 83% ± 15% (±95% confidence interval) of patients experienced a symptomatic response to treatment. Local control at the skull base was 95 ± 9% at 2 years and 78 ± 23% at 3 years. Local-regional control above the clavicles was 75 ± 15% at 1 year and 51 ± 20% at 2 years. Overall and cause specific survival were identical, 82 ± 13% at 1 year, 76 ± 14% at 2 years, and 72 ± 16% at 3 years. One patient developed a radiation-induced optic neuropathy 12 months after radiosurgery. Conclusion: Stereotactic radiosurgery using the Leksell Gamma Unit can provide durable tumor control and symptomatic relief with acceptable toxicity in the majority of patients with malignant tumors 4 cm or less in size involving the skull base. Further evaluation of more patients with longer follow-up is warranted

  10. Mid-Ventilation Concept for Mobile Pulmonary Tumors: Internal Tumor Trajectory Versus Selective Reconstruction of Four-Dimensional Computed Tomography Frames Based on External Breathing Motion

    International Nuclear Information System (INIS)

    Guckenberger, Matthias; Wilbert, Juergen; Krieger, Thomas; Richter, Anne; Baier, Kurt; Flentje, Michael

    2009-01-01

    Purpose: To evaluate the accuracy of direct reconstruction of mid-ventilation and peak-phase four-dimensional (4D) computed tomography (CT) frames based on the external breathing signal. Methods and Materials: For 11 patients with 15 pulmonary targets, a respiration-correlated CT study (4D CT) was acquired for treatment planning. After retrospective time-based sorting of raw projection data and reconstruction of eight CT frames equally distributed over the breathing cycle, mean tumor position (P mean ), mid-ventilation frame, and breathing motion were evaluated based on the internal tumor trajectory. Analysis of the external breathing signal (pressure sensor around abdomen) with amplitude-based sorting of projections was performed for direct reconstruction of the mid-ventilation frame and frames at peak phases of the breathing cycle. Results: On the basis of the eight 4D CT frames equally spaced in time, tumor motion was largest in the craniocaudal direction, with 12 ± 7 mm on average. Tumor motion between the two frames reconstructed at peak phases was not different in the craniocaudal and anterior-posterior directions but was systematically smaller in the left-right direction by 1 mm on average. The 3-dimensional distance between P mean and the tumor position in the mid-ventilation frame based on the internal tumor trajectory was 1.2 ± 1 mm. Reconstruction of the mid-ventilation frame at the mean amplitude position of the external breathing signal resulted in tumor positions 2.0 ± 1.1 mm distant from P mean . Breathing-induced motion artifacts in mid-ventilation frames caused negligible changes in tumor volume and shape. Conclusions: Direct reconstruction of the mid-ventilation frame and frames at peak phases based on the external breathing signal was reliable. This makes the reconstruction of only three 4D CT frames sufficient for application of the mid-ventilation technique in clinical practice.

  11. Image-based modeling of tumor shrinkage in head and neck radiation therapy1

    Science.gov (United States)

    Chao, Ming; Xie, Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing, Lei

    2010-01-01

    Purpose: Understanding the kinetics of tumor growth∕shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the “ground truth” with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy. PMID:20527569

  12. Image-based modeling of tumor shrinkage in head and neck radiation therapy

    International Nuclear Information System (INIS)

    Chao Ming; Xie Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing Lei

    2010-01-01

    Purpose: Understanding the kinetics of tumor growth/shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the ''ground truth'' with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy.

  13. Image-based modeling of tumor shrinkage in head and neck radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chao Ming; Xie Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing Lei [Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 and Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205-1799 (United States); Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States); Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205-1799 (United States); Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States)

    2010-05-15

    Purpose: Understanding the kinetics of tumor growth/shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the ''ground truth'' with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy.

  14. Value-Based Medicine and Integration of Tumor Biology.

    Science.gov (United States)

    Brooks, Gabriel A; Bosserman, Linda D; Mambetsariev, Isa; Salgia, Ravi

    2017-01-01

    Clinical oncology is in the midst of a genomic revolution, as molecular insights redefine our understanding of cancer biology. Greater awareness of the distinct aberrations that drive carcinogenesis is also contributing to a growing armamentarium of genomically targeted therapies. Although much work remains to better understand how to combine and sequence these therapies, improved outcomes for patients are becoming manifest. As we welcome this genomic revolution in cancer care, oncologists also must grapple with a number of practical problems. Costs of cancer care continue to grow, with targeted therapies responsible for an increasing proportion of spending. Rising costs are bringing the concept of value into sharper focus and challenging the oncology community with implementation of value-based cancer care. This article explores the ways that the genomic revolution is transforming cancer care, describes various frameworks for considering the value of genomically targeted therapies, and outlines key challenges for delivering on the promise of personalized cancer care. It highlights practical solutions for the implementation of value-based care, including investment in biomarker development and clinical trials to improve the efficacy of targeted therapy, the use of evidence-based clinical pathways, team-based care, computerized clinical decision support, and value-based payment approaches.

  15. Breast tumor segmentation in high resolution x-ray phase contrast analyzer based computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Brun, E., E-mail: emmanuel.brun@esrf.fr [European Synchrotron Radiation Facility (ESRF), Grenoble 380000, France and Department of Physics, Ludwig-Maximilians University, Garching 85748 (Germany); Grandl, S.; Sztrókay-Gaul, A.; Gasilov, S. [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, 81377 Munich (Germany); Barbone, G. [Department of Physics, Harvard University, Cambridge, Massachusetts 02138 (United States); Mittone, A.; Coan, P. [Department of Physics, Ludwig-Maximilians University, Garching 85748, Germany and Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, 81377 Munich (Germany); Bravin, A. [European Synchrotron Radiation Facility (ESRF), Grenoble 380000 (France)

    2014-11-01

    Purpose: Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human-guided breast tumor segmentation. This method has been applied to high-resolution images of excised human organs, each of several gigabytes. Methods: The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure’s possible applications. Results: A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists. Conclusions: The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high-resolution x-ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.

  16. Breast tumor segmentation in high resolution x-ray phase contrast analyzer based computed tomography.

    Science.gov (United States)

    Brun, E; Grandl, S; Sztrókay-Gaul, A; Barbone, G; Mittone, A; Gasilov, S; Bravin, A; Coan, P

    2014-11-01

    Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human-guided breast tumor segmentation. This method has been applied to high-resolution images of excised human organs, each of several gigabytes. The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure's possible applications. A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists. The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high-resolution x-ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.

  17. Tumor type resulting in upgrade: An analysis based on 333 low grade soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Langer, Stefan

    2014-11-01

    Full Text Available [english] Introduction: Soft tissue sarcomas (STS are rare tumors. Based on histopathological criteria, three grades are distinguished from low (G1 to intermediate (G2 and high grade (G3. After complete initial surgical resection, some G1 STS recur as lesions with an upgrade of a previous G1 STS to a recurrent G2 STS. This upgrade indicates higher malignancy of the STS. Our aim was to find possible risk factors for these upgrades including age, localization of tumor and tumor type. Methods: This retrospective case-control study evaluated 333 patients. Of these 333, 54.7% were male and 45.3% female. All patients underwent R0 resections and among these, 10% subsequently upgraded. The processed data include age, gender, tumor type, tumor localization, local recurrence and upgrade. Results: Patients with upgrades have a higher mean age of 5.5 years than our reference collective. The tumor type has a significant effect on upgrades. Patients with fibrosarcomas are at a threefold risk of an upgrade compared to patients with other G1 STS.Conclusion: Our results indicate that age and tumor type play a key role in upgrades in G1 STS. Patients, age 60 and above and diagnosed with G1 fibrosarcomas, are three times as likely to upgrade compared to patients younger than 60 with other G1 STS. We discuss the significance of these risk factors and whether aside from complete tumor resection, additional therapies (e.g. irradiation may be applied to improve therapeutic outcome.

  18. Nanostructures based on alumina hydroxides inhibit tumor growth

    Science.gov (United States)

    Fomenko, A. N.; Korovin, M. S.

    2017-09-01

    Nanoparticles and nanostructured materials are one of the most promising developments for cancer therapy. Gold nanoparticles, magnetic nanoparticles based on iron and its oxides and other metal oxides have been widely used in diagnosis and treatment of cancer. Much less research attention has been payed to nanoparticles and nanostructures based on aluminum oxides and hydroxides as materials for cancer diagnosis and treatment. However recent investigations have shown promising results regarding these objects. Here, we review the antitumor results obtained with AlOOH nanoparticles.

  19. A consumer study of entire male pigs

    DEFF Research Database (Denmark)

    Godt, Jannik; Kristensen, Kai; Poulsen, Carsten Stig

    1996-01-01

    made in-home by consumers, thus bringing the analysis out of the laboratory and into the market place. The vast majority of the population of uncastrated male pigs have low concentrations of skatole and androstenone. The cutlets that were evaluated in this study were selected from uncastrated male pigs...... on a number of castrated male pigs and gilts. No difference was found in the way the odour components affected the eating quality determined by men and women. A total of 5.4% of the consumers in the study reacted negatively in their evaluation of the eating quality of the cutlets selected for the study......Former studies of the unpleasant odour of meat from certain uncastrated male pigs have been based mainly on evaluations made by trained sensory panellists. This study analyses the effect of the two dominating male pig odour components, skatole and androstenone, on the evaluation of eating quality...

  20. A Consumer Study of Entire Male Pigs

    DEFF Research Database (Denmark)

    Poulsen, Carsten Stig; Godt, J.; Kristensen, K.

    1996-01-01

    Former studies of the unpleasant odour of meat from certain uncastrated male pigs have been based mainly on evaluations made by trained sensory panellists. This study analyses the effect of the two dominating male pig odour components, skatole and androstenone, on the evaluation of eating quality...... made in-home by consumers, thus bringing the analysis out of the laboratory and into the market place. The vast majority of the population of uncastrated male pigs have low concentrations of skatole and androstenone. The cutlets that were evaluated in this study were selected from uncastrated male pigs...... on a number of castrated male pigs and gilts. No difference was found in the way the odour components affected the eating quality determined by men and women. A total of 5.4% of the consumers in the study reacted negatively in their evaluation of the eating quality of the cutlets selected for the study...

  1. WE-E-17A-01: Characterization of An Imaging-Based Model of Tumor Angiogenesis

    International Nuclear Information System (INIS)

    Adhikarla, V; Jeraj, R

    2014-01-01

    Purpose: Understanding the transient dynamics of tumor oxygenation is important when evaluating tumor-vasculature response to anti-angiogenic therapies. An imaging-based tumor-vasculature model was used to elucidate factors that affect these dynamics. Methods: Tumor growth depends on its doubling time (Td). Hypoxia increases pro-angiogenic factor (VEGF) concentration which is modeled to reduce vessel perfusion, attributing to its effect of increasing vascular permeability. Perfused vessel recruitment depends on the existing perfused vasculature, VEGF concentration and maximum VEGF concentration (VEGFmax) for vessel dysfunction. A convolution-based algorithm couples the tumor to the normal tissue vessel density (VD-nt). The parameters are benchmarked to published pre-clinical data and a sensitivity study evaluating the changes in the peak and time to peak tumor oxygenation characterizes them. The model is used to simulate changes in hypoxia and proliferation PET imaging data obtained using [Cu- 61]Cu-ATSM and [F-18]FLT respectively. Results: Td and VD-nt were found to be the most influential on peak tumor pO2 while VEGFmax was marginally influential. A +20 % change in Td, VD-nt and VEGFmax resulted in +50%, +25% and +5% increase in peak pO2. In contrast, Td was the most influential on the time to peak oxygenation with VD-nt and VEGFmax playing marginal roles. A +20% change in Td, VD-nt and VEGFmax increased the time to peak pO2 by +50%, +5% and +0%. A −20% change in the above parameters resulted in comparable decreases in the peak and time to peak pO2. Model application to the PET data was able to demonstrate the voxel-specific changes in hypoxia of the imaged tumor. Conclusion: Tumor-specific doubling time and vessel density are important parameters to be considered when evaluating hypoxia transients. While the current model simulates the oxygen dynamics of an untreated tumor, incorporation of therapeutic effects can make the model a potent tool for analyzing

  2. Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors.

    Science.gov (United States)

    Zhang, Bing-Lan; Qin, Di-Yuan; Mo, Ze-Ming; Li, Yi; Wei, Wei; Wang, Yong-Sheng; Wang, Wei; Wei, Yu-Quan

    2016-04-01

    Recent reports on the impressive efficacy of chimeric antigen receptor (CAR)-modified T cells against hematologic malignancies have inspired oncologists to extend these efforts for the treatment of solid tumors. Clinical trials of CAR-T-based cancer immunotherapy for solid tumors showed that the efficacies are not as remarkable as in the case of hematologic malignancies. There are several challenges that researchers must face when treating solid cancers with CAR-T cells, these include choosing an ideal target, promoting efficient trafficking and infiltration, overcoming the immunosuppressive microenvironment, and avoiding associated toxicity. In this review, we discuss the obstacles imposed by solid tumors on CAR-T cell-based immunotherapy and strategies adopted to improve the therapeutic potential of this approach. Continued investigations are necessary to improve therapeutic outcomes and decrease the adverse effects of CAR-T cell therapy in patients with solid malignancies in the future.

  3. Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Ruixiang Li

    2018-01-01

    Full Text Available Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems (fast elimination in circulation to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles (CMBNPs are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.

  4. Optimizing a waveguide-based sandwich immunoassay for tumor biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Mukundan, Harshini [Los Alamos National Laboratory; Swanson, Basil I [Los Alamos National Laboratory; Xie, Hongzhi [Los Alamos National Laboratory; Anderson, Aaron S [Los Alamos National Laboratory; Grace, W Kevin [Los Alamos National Laboratory; Shively, John E [NON LANL

    2008-01-01

    The sensor team at the Los Alamos National Laboratory has developed a waveguide-based optical biosensor for the detection of biomarkers associated with the disease. We have previously demonstrated the application of this technology to the sensitive detection of carcinoembryonic antigen in serum and nipple aspirate fluid from breast cancer patients. In this publication, we report improvements to this technology that will facilitate transition to a point-of-care diagnostic system and/or robust research tool.

  5. Multimodal navigated skull base tumor resection using image-based vascular and cranial nerve segmentation: A prospective pilot study.

    Science.gov (United States)

    Dolati, Parviz; Gokoglu, Abdulkerim; Eichberg, Daniel; Zamani, Amir; Golby, Alexandra; Al-Mefty, Ossama

    2015-01-01

    Skull base tumors frequently encase or invade adjacent normal neurovascular structures. For this reason, optimal tumor resection with incomplete knowledge of patient anatomy remains a challenge. To determine the accuracy and utility of image-based preoperative segmentation in skull base tumor resections, we performed a prospective study. Ten patients with skull base tumors underwent preoperative 3T magnetic resonance imaging, which included thin section three-dimensional (3D) space T2, 3D time of flight, and magnetization-prepared rapid acquisition gradient echo sequences. Imaging sequences were loaded in the neuronavigation system for segmentation and preoperative planning. Five different neurovascular landmarks were identified in each case and measured for accuracy using the neuronavigation system. Each segmented neurovascular element was validated by manual placement of the navigation probe, and errors of localization were measured. Strong correspondence between image-based segmentation and microscopic view was found at the surface of the tumor and tumor-normal brain interfaces in all cases. The accuracy of the measurements was 0.45 ± 0.21 mm (mean ± standard deviation). This information reassured the surgeon and prevented vascular injury intraoperatively. Preoperative segmentation of the related cranial nerves was possible in 80% of cases and helped the surgeon localize involved cranial nerves in all cases. Image-based preoperative vascular and neural element segmentation with 3D reconstruction is highly informative preoperatively and could increase the vigilance of neurosurgeons for preventing neurovascular injury during skull base surgeries. Additionally, the accuracy found in this study is superior to previously reported measurements. This novel preliminary study is encouraging for future validation with larger numbers of patients.

  6. Saponin-based adjuvants create a highly effective anti-tumor vaccine when combined with in situ tumor destruction.

    NARCIS (Netherlands)

    Brok, M.H.M.G.M. den; Nierkens, S.; Wagenaars, J.A.L.; Ruers, T.J.M.; Schrier, C.C.; Rijke, E.O.; Adema, G.J.

    2012-01-01

    Today's most commonly used microbial vaccines are essentially composed of antigenic elements and a non-microbial adjuvant, and induce solid amounts of antibodies. Cancer vaccines mostly aim to induce anti-tumor CTL-responses, which require cross-presentation of tumor-derived antigens by dendritic

  7. Texture-based classification of different gastric tumors at contrast-enhanced CT

    Energy Technology Data Exchange (ETDEWEB)

    Ba-Ssalamah, Ahmed, E-mail: ahmed.ba-ssalamah@meduniwien.ac.at [Department of Radiology, Medical University of Vienna (Austria); Muin, Dina; Schernthaner, Ruediger; Kulinna-Cosentini, Christiana; Bastati, Nina [Department of Radiology, Medical University of Vienna (Austria); Stift, Judith [Department of Pathology, Medical University of Vienna (Austria); Gore, Richard [Department of Radiology, University of Chicago Pritzker School of Medicine, Chicago, IL (United States); Mayerhoefer, Marius E. [Department of Radiology, Medical University of Vienna (Austria)

    2013-10-01

    Purpose: To determine the feasibility of texture analysis for the classification of gastric adenocarcinoma, lymphoma, and gastrointestinal stromal tumors on contrast-enhanced hydrodynamic-MDCT images. Materials and methods: The arterial phase scans of 47 patients with adenocarcinoma (AC) and a histologic tumor grade of [AC-G1, n = 4, G1, n = 4; AC-G2, n = 7; AC-G3, n = 16]; GIST, n = 15; and lymphoma, n = 5, and the venous phase scans of 48 patients with AC-G1, n = 3; AC-G2, n = 6; AC-G3, n = 14; GIST, n = 17; lymphoma, n = 8, were retrospectively reviewed. Based on regions of interest, texture analysis was performed, and features derived from the gray-level histogram, run-length and co-occurrence matrix, absolute gradient, autoregressive model, and wavelet transform were calculated. Fisher coefficients, probability of classification error, average correlation coefficients, and mutual information coefficients were used to create combinations of texture features that were optimized for tumor differentiation. Linear discriminant analysis in combination with a k-nearest neighbor classifier was used for tumor classification. Results: On arterial-phase scans, texture-based lesion classification was highly successful in differentiating between AC and lymphoma, and GIST and lymphoma, with misclassification rates of 3.1% and 0%, respectively. On venous-phase scans, texture-based classification was slightly less successful for AC vs. lymphoma (9.7% misclassification) and GIST vs. lymphoma (8% misclassification), but enabled the differentiation between AC and GIST (10% misclassification), and between the different grades of AC (4.4% misclassification). No texture feature combination was able to adequately distinguish between all three tumor types. Conclusion: Classification of different gastric tumors based on textural information may aid radiologists in establishing the correct diagnosis, at least in cases where the differential diagnosis can be narrowed down to two

  8. Texture-based classification of different gastric tumors at contrast-enhanced CT

    International Nuclear Information System (INIS)

    Ba-Ssalamah, Ahmed; Muin, Dina; Schernthaner, Ruediger; Kulinna-Cosentini, Christiana; Bastati, Nina; Stift, Judith; Gore, Richard; Mayerhoefer, Marius E.

    2013-01-01

    Purpose: To determine the feasibility of texture analysis for the classification of gastric adenocarcinoma, lymphoma, and gastrointestinal stromal tumors on contrast-enhanced hydrodynamic-MDCT images. Materials and methods: The arterial phase scans of 47 patients with adenocarcinoma (AC) and a histologic tumor grade of [AC-G1, n = 4, G1, n = 4; AC-G2, n = 7; AC-G3, n = 16]; GIST, n = 15; and lymphoma, n = 5, and the venous phase scans of 48 patients with AC-G1, n = 3; AC-G2, n = 6; AC-G3, n = 14; GIST, n = 17; lymphoma, n = 8, were retrospectively reviewed. Based on regions of interest, texture analysis was performed, and features derived from the gray-level histogram, run-length and co-occurrence matrix, absolute gradient, autoregressive model, and wavelet transform were calculated. Fisher coefficients, probability of classification error, average correlation coefficients, and mutual information coefficients were used to create combinations of texture features that were optimized for tumor differentiation. Linear discriminant analysis in combination with a k-nearest neighbor classifier was used for tumor classification. Results: On arterial-phase scans, texture-based lesion classification was highly successful in differentiating between AC and lymphoma, and GIST and lymphoma, with misclassification rates of 3.1% and 0%, respectively. On venous-phase scans, texture-based classification was slightly less successful for AC vs. lymphoma (9.7% misclassification) and GIST vs. lymphoma (8% misclassification), but enabled the differentiation between AC and GIST (10% misclassification), and between the different grades of AC (4.4% misclassification). No texture feature combination was able to adequately distinguish between all three tumor types. Conclusion: Classification of different gastric tumors based on textural information may aid radiologists in establishing the correct diagnosis, at least in cases where the differential diagnosis can be narrowed down to two

  9. Targeted Tumor Therapy Based on Nanodiamonds Decorated with Doxorubicin and Folic Acid.

    Science.gov (United States)

    Ryu, Tae-Kyung; Baek, Seung Woon; Lee, Gyoung-Ja; Rhee, Chang-Kyu; Choi, Sung-Wook

    2017-02-01

    The fabrication of nanodiamond (ND)-based drug carriers for tumor-targeted drug delivery is described. The ND clusters with an average size of 52.84 nm are fabricated using a simple fluidic device combined with a precipitation method and then conjugated with folic acid (FA) and doxorubicin (Dox) via carbodiimide chemistry to obtain FA/Dox-modified ND (FA/Dox-ND) clusters. Cell culture experiments revealed that KB (folate receptor-positive) cells are preferentially ablated by FA/Dox-ND clusters compared to A549 (folate receptor-negative) cells. In vivo results revealed that FA/Dox-ND clusters are specifically accumulated in tumor tissues after intravenous injection into tumor-bearing mice, effectively reducing the volume of tumor. Based on these results, this study suggests that FA/Dox-ND clusters can be a good candidate as tumor-targeted nanovehicles for delivery of antitumor drug. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016

    DEFF Research Database (Denmark)

    Lugli, Alessandro; Kirsch, Richard; Ajioka, Yoichi

    2017-01-01

    to determine the strength of recommendations and quality of evidence. The following 10 statements achieved consensus: Tumor budding is defined as a single tumor cell or a cell cluster consisting of four tumor cells or less (22/22, 100%). Tumor budding is an independent predictor of lymph node metastases in pT1......%). Intratumoral budding exists in colorectal cancer and has been shown to be related to lymph node metastasis (22/22, 100%). Tumor budding is assessed in one hotspot (in a field measuring 0.785 mm 2) at the invasive front (22/22, 100%). A three-tier system should be used along with the budding count in order...

  11. Radiological classification of renal angiomyolipomas based on 127 tumors

    Directory of Open Access Journals (Sweden)

    Prando Adilson

    2003-01-01

    Full Text Available PURPOSE: Demonstrate radiological findings of 127 angiomyolipomas (AMLs and propose a classification based on the radiological evidence of fat. MATERIALS AND METHODS: The imaging findings of 85 consecutive patients with AMLs: isolated (n = 73, multiple without tuberous sclerosis (TS (n = 4 and multiple with TS (n = 8, were retrospectively reviewed. Eighteen AMLs (14% presented with hemorrhage. All patients were submitted to a dedicated helical CT or magnetic resonance studies. All hemorrhagic and non-hemorrhagic lesions were grouped together since our objective was to analyze the presence of detectable fat. Out of 85 patients, 53 were monitored and 32 were treated surgically due to large perirenal component (n = 13, hemorrhage (n = 11 and impossibility of an adequate preoperative characterization (n = 8. There was not a case of renal cell carcinoma (RCC with fat component in this group of patients. RESULTS: Based on the presence and amount of detectable fat within the lesion, AMLs were classified in 4 distinct radiological patterns: Pattern-I, predominantly fatty (usually less than 2 cm in diameter and intrarenal: 54%; Pattern-II, partially fatty (intrarenal or exophytic: 29%; Pattern-III, minimally fatty (most exophytic and perirenal: 11%; and Pattern-IV, without fat (most exophytic and perirenal: 6%. CONCLUSIONS: This proposed classification might be useful to understand the imaging manifestations of AMLs, their differential diagnosis and determine when further radiological evaluation would be necessary. Small (< 1.5 cm, pattern-I AMLs tend to be intra-renal, homogeneous and predominantly fatty. As they grow they tend to be partially or completely exophytic and heterogeneous (patterns II and III. The rare pattern-IV AMLs, however, can be small or large, intra-renal or exophytic but are always homogeneous and hyperdense mass. Since no renal cell carcinoma was found in our series, from an evidence-based practice, all renal mass with detectable

  12. Characterizing spatiotemporal information loss in sparse-sampling-based dynamic MRI for monitoring respiration-induced tumor motion in radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Tatsuya J. [Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas 75390 (United States); Nofiele, Joris; Yuan, Qing [Department of Radiology, UT Southwestern Medical Center, Dallas, Texas 75390 (United States); Madhuranthakam, Ananth J.; Pedrosa, Ivan; Chopra, Rajiv [Department of Radiology, UT Southwestern Medical Center, Dallas, Texas 75390 (United States); Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas 75390 (United States); Sawant, Amit, E-mail: amit.sawant@utsouthwestern.edu [Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas 75390 (United States); Department of Radiology, UT Southwestern Medical Center, Dallas, Texas 75390 (United States); Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201 (United States)

    2016-06-15

    .4 mm, which was smaller than the reconstructed pixel resolution of 0.67 mm. In the patient study, the dynamic 2D MRI enabled the monitoring of cycle-to-cycle respiratory variability present in the tumor position. It was seen that the range of centroid motion as well as the area covered due to target motion during each individual respiratory cycle was underestimated compared to the entire motion range observed over multiple breathing cycles. Conclusions: The authors’ initial results demonstrate that sparse-sampling- and reconstruction-based dynamic MRI can be used to achieve adequate image acquisition speeds without significant information loss for the task of radiotherapy guidance. Such monitoring can yield spatial and temporal information superior to conventional offline and online motion capture methods used in thoracic and abdominal radiotherapy.

  13. Dose painting based on tumor uptake of Cu-ATSM and FDG

    DEFF Research Database (Denmark)

    Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael

    2014-01-01

    definitions based on FDG, 64Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64Cu-ATSM at two different time-points and FDG provide different biological information that has to be taken into account when using the dose painting...

  14. Dose painting based on tumor uptake of Cu-ATSM and FDG

    DEFF Research Database (Denmark)

    Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael

    2014-01-01

    Background: Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[18 F]- fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis...

  15. Visual outcome after fractionated stereotactic radiation therapy of benign anterior skull base tumors

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Wiencke, Anne Katrine; Munck af Rosenschold, Per

    2014-01-01

    To determine visual outcome including the occurrence of radiation induced optic neuropathy (RION) as well as tumor control after fractionated stereotactic radiation therapy (FSRT) of benign anterior skull base meningiomas or pituitary adenomas. Thirty-nine patients treated with FSRT for anterior...

  16. Correcting for catchment area nonresidency in studies based on tumor-registry data

    International Nuclear Information System (INIS)

    Sposto, R.; Preston, D.L.

    1993-05-01

    We discuss the effect of catchment area nonresidency on estimates of cancer incidence from a tumor-registry-based cohort study and demonstrate that a relatively simple correction is possible in the context of Poisson regression analysis if individual residency histories or the probabilities of residency are known. A comparison of a complete data maximum likelihood analysis with several Poisson regression analyses demonstrates the adequacy of the simple correction in a large simulated data set. We compare analyses of stomach-cancer incidence from the Radiation Effects Research Foundation tumor registry with and without the correction. We also discuss some implications of including cases identified only on the basis of death certificates. (author)

  17. A statistical method for lung tumor segmentation uncertainty in PET images based on user inference.

    Science.gov (United States)

    Zheng, Chaojie; Wang, Xiuying; Feng, Dagan

    2015-01-01

    PET has been widely accepted as an effective imaging modality for lung tumor diagnosis and treatment. However, standard criteria for delineating tumor boundary from PET are yet to develop largely due to relatively low quality of PET images, uncertain tumor boundary definition, and variety of tumor characteristics. In this paper, we propose a statistical solution to segmentation uncertainty on the basis of user inference. We firstly define the uncertainty segmentation band on the basis of segmentation probability map constructed from Random Walks (RW) algorithm; and then based on the extracted features of the user inference, we use Principle Component Analysis (PCA) to formulate the statistical model for labeling the uncertainty band. We validated our method on 10 lung PET-CT phantom studies from the public RIDER collections [1] and 16 clinical PET studies where tumors were manually delineated by two experienced radiologists. The methods were validated using Dice similarity coefficient (DSC) to measure the spatial volume overlap. Our method achieved an average DSC of 0.878 ± 0.078 on phantom studies and 0.835 ± 0.039 on clinical studies.

  18. Tumor recognition in wireless capsule endoscopy images using textural features and SVM-based feature selection.

    Science.gov (United States)

    Li, Baopu; Meng, Max Q-H

    2012-05-01

    Tumor in digestive tract is a common disease and wireless capsule endoscopy (WCE) is a relatively new technology to examine diseases for digestive tract especially for small intestine. This paper addresses the problem of automatic recognition of tumor for WCE images. Candidate color texture feature that integrates uniform local binary pattern and wavelet is proposed to characterize WCE images. The proposed features are invariant to illumination change and describe multiresolution characteristics of WCE images. Two feature selection approaches based on support vector machine, sequential forward floating selection and recursive feature elimination, are further employed to refine the proposed features for improving the detection accuracy. Extensive experiments validate that the proposed computer-aided diagnosis system achieves a promising tumor recognition accuracy of 92.4% in WCE images on our collected data.

  19. Reconstruction of the cranial base in surgery for jugular foramen tumors.

    Science.gov (United States)

    Ramina, Ricardo; Maniglia, Joao J; Paschoal, Jorge R; Fernandes, Yvens B; Neto, Mauricio Coelho; Honorato, Donizeti C

    2005-04-01

    The surgical removal of a jugular foramen (JF) tumor presents the neurosurgeon with a complex management problem that requires an understanding of the natural history, diagnosis, surgical approaches, and postoperative complications. Cerebrospinal fluid (CSF) leakage is one of the most common complications of this surgery. Different surgical approaches and management concepts to avoid this complication have been described, mainly in the ear, nose, and throat literature. The purpose of this study was to review the results of CSF leakage prevention in a series of 66 patients with JF tumors operated on by a multidisciplinary cranial base team using a new technique for cranial base reconstruction. We retrospectively studied 66 patients who had JF tumors with intracranial extension and who underwent surgical treatment in our institutions from January 1987 to December 2001. Paragangliomas were the most frequent lesions, followed by schwannomas and meningiomas. All patients were operated on using the same multidisciplinary surgical approach (neurosurgeons and ear, nose, and throat surgeons). A surgical strategy for reconstruction of the cranial base using vascularized flaps was carried out. The closure of the surgical wound was performed in three layers. A specially developed myofascial flap (temporalis fascia, cervical fascia, and sternocleidomastoid muscle) associated to the inferior rotation of the posterior portion of the temporalis muscle was used to reconstruct the cranial base with vascularized flaps. In this series of 66 patients, postoperative CSF leakage developed in three cases. These patients presented with very large or recurrent tumors, and the postoperative CSF fistulae were surgically closed. The cosmetic result obtained with this reconstruction was classified as excellent or good in all patients. Our results compare favorably with those reported in the literature. The surgical strategy used for cranial base reconstruction presented in this article has

  20. [Neurophysiological identification of the cranial nerves in endoscopic endonasal surgery of skull base tumors].

    Science.gov (United States)

    Shkarubo, A N; Ogurtsova, A A; Moshchev, D A; Lubnin, A Yu; Andreev, D N; Koval', K V; Chernov, I V

    2016-01-01

    Intraoperative identification of the cranial nerves is a useful technique in removal of skull base tumors through the endoscopic endonasal approach. Searching through the scientific literature found one pilot study on the use of triggered electromyography (t-EMG) for identification of the VIth nerve in endonasal endoscopic surgery of skull base tumors (D. San-Juan, et al, 2014). The study objective was to prevent iatrogenic injuries to the cranial nerves without reducing the completeness of tumor tissue resection. In 2014, 5 patients were operated on using the endoscopic endonasal approach. Surgeries were performed for large skull base chordomas (2 cases) and trigeminal nerve neurinomas located in the cavernous sinus (3). Intraoperatively, identification of the cranial nerves was performed by triggered electromyography using a bipolar electrode (except 1 case of chordoma where a monopolar electrode was used). Evaluation of the functional activity of the cranial nerves was carried out both preoperatively and postoperatively. Tumor resection was total in 4 out of 5 cases and subtotal (chordoma) in 1 case. Intraoperatively, the IIIrd (2 patients), Vth (2), and VIth (4) cranial nerves were identified. No deterioration in the function of the intraoperatively identified nerves was observed in the postoperative period. In one case, no responses from the VIth nerve on the right (in the cavernous sinus region) were intraoperatively obtained, and deep paresis (up to plegia) of the nerve-innervated muscles developed in the postoperative period. The nerve function was not impaired before surgery. The t-EMG technique is promising and requires further research.

  1. Implicit function with natural behavior over entire domain

    International Nuclear Information System (INIS)

    Itoh, Taku; Saitoh, Ayumu; Kamitani, Atsushi; Nakamura, Hiroaki

    2012-01-01

    To generate a smooth implicit function that behaves naturally over an entire domain, a method to smoothly combine an implicit function f(x) with a global support function g(x) has been proposed. The proposed method can be applied to large scattered point data, since the implicit function f(x) is generated by a partition-of-unity-based method. The global support function g(x) is generated by a radial basis function-based method or by the least-squares method. To ensure a smooth combination of f(x) and g(x), an appropriate weight function is employed. In numerical experiments, the proposed method is applied to large point data. The results illustrate that the proposed method can generate a smooth implicit function F(x) with natural behavior over the entire domain. In addition, on the given points, the accuracy of F(x) is exactly the same as that of f(x). Furthermore, the computational cost for generation of F(x) is almost the same as that of f(x). (author)

  2. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    OpenAIRE

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.; Bruns, Christiane J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associa...

  3. A Novel Markerless Technique to Evaluate Daily Lung Tumor Motion Based on Conventional Cone-Beam CT Projection Data

    International Nuclear Information System (INIS)

    Yang Yin; Zhong Zichun; Guo Xiaohu; Wang Jing; Anderson, John; Solberg, Timothy; Mao Weihua

    2012-01-01

    Purpose: In this study, we present a novel markerless technique, based on cone beam computed tomography (CBCT) raw projection data, to evaluate lung tumor daily motion. Method and Materials: The markerless technique, which uses raw CBCT projection data and locates tumors directly on every projection, consists of three steps. First, the tumor contour on the planning CT is used to create digitally reconstructed radiographs (DRRs) at every projection angle. Two sets of DRRs are created: one showing only the tumor, and another with the complete anatomy without the tumor. Second, a rigid two-dimensional image registration is performed to register the DRR set without the tumor to the CBCT projections. After the registration, the projections are subtracted from the DRRs, resulting in a projection dataset containing primarily tumor. Finally, a second registration is performed between the subtracted projection and tumor-only DRR. The methodology was evaluated using a chest phantom containing a moving tumor, and retrospectively in 4 lung cancer patients treated by stereotactic body radiation therapy. Tumors detected on projection images were compared with those from three-dimensional (3D) and four-dimensional (4D) CBCT reconstruction results. Results: Results in both static and moving phantoms demonstrate that the accuracy is within 1 mm. The subsequent application to 22 sets of CBCT scan raw projection data of 4 lung cancer patients includes about 11,000 projections, with the detected tumor locations consistent with 3D and 4D CBCT reconstruction results. This technique reveals detailed lung tumor motion and provides additional information than conventional 4D images. Conclusion: This technique is capable of accurately characterizing lung tumor motion on a daily basis based on a conventional CBCT scan. It provides daily verification of the tumor motion to ensure that these motions are within prior estimation and covered by the treatment planning volume.

  4. The value of blood oxygenation level-dependent (BOLD MR imaging in differentiation of renal solid mass and grading of renal cell carcinoma (RCC: analysis based on the largest cross-sectional area versus the entire whole tumour.

    Directory of Open Access Journals (Sweden)

    Guang-Yu Wu

    Full Text Available To study the value of assessing renal masses using different methods in parameter approaches and to determine whether BOLD MRI is helpful in differentiating RCC from benign renal masses, differentiating clear-cell RCC from renal masses other than clear-cell RCC and determining the tumour grade.Ninety-five patients with 139 renal masses (93 malignant and 46 benign who underwent abdominal BOLD MRI were enrolled. R2* values were derived from the largest cross-section (R2*largest and from the whole tumour (R2*whole. Intra-observer and inter-observer agreements were analysed based on two measurements by the same observer and the first measurement from each observer, respectively, and these agreements are reported with intra-class correlation coefficients and 95% confidence intervals. The diagnostic value of the R2* value in the evaluation was assessed with receiver-operating characteristic analysis.The intra-observer agreement was very good for R2*largest and R2*whole (all > 0.8. The inter-observer agreement of R2*whole (0.75, 95% confidence interval: 0.69~0.79 was good and was significantly improved compared with the R2*largest (0.61, 95% confidence interval: 0.52~0.68, as there was no overlap in the 95% confidence interval of the intra-class correlation coefficients. The diagnostic value in differentiating renal cell carcinoma from benign lesions with R2*whole (AUC=0.79/0.78[observer1/observer2] and R2*largest (AUC=0.75[observer1] was good and significantly higher (p=0.01 for R2*largest[observer2] vs R2*whole[observer2], p 0.7 and were not significantly different (p=0.89/0.93 for R2*largest vs R2*whole[observer1/observer2], 0.96 for R2*whole[observer1] vs R2*largest[observer2] and 0.96 for R2*whole [observer2] vs R2*largest[observer1].BOLD MRI could provide a feasible parameter for differentiating renal cell carcinoma from benign renal masses and for predicting clear-cell renal cell carcinoma grading. Compared with the largest cross

  5. Tumor Suppressor Gene-Based Nanotherapy: From Test Tube to the Clinic

    Directory of Open Access Journals (Sweden)

    Manish Shanker

    2011-01-01

    Full Text Available Cancer is a major health problem in the world. Advances made in cancer therapy have improved the survival of patients in certain types of cancer. However, the overall five-year survival has not significantly improved in the majority of cancer types. Major challenges encountered in having effective cancer therapy are development of drug resistance by the tumor cells, nonspecific cytotoxicity, and inability to affect metastatic tumors by the chemodrugs. Overcoming these challenges requires development and testing of novel therapies. One attractive cancer therapeutic approach is cancer gene therapy. Several laboratories including the authors' laboratory have been investigating nonviral formulations for delivering therapeutic genes as a mode for effective cancer therapy. In this paper the authors will summarize their experience in the development and testing of a cationic lipid-based nanocarrier formulation and the results from their preclinical studies leading to a Phase I clinical trial for nonsmall cell lung cancer. Their nanocarrier formulation containing therapeutic genes such as tumor suppressor genes when administered intravenously effectively controls metastatic tumor growth. Additional Phase I clinical trials based on the results of their nanocarrier formulation have been initiated or proposed for treatment of cancer of the breast, ovary, pancreas, and metastatic melanoma, and will be discussed.

  6. Tumor suppressor gene-based nanotherapy: from test tube to the clinic.

    Science.gov (United States)

    Shanker, Manish; Jin, Jiankang; Branch, Cynthia D; Miyamoto, Shinya; Grimm, Elizabeth A; Roth, Jack A; Ramesh, Rajagopal

    2011-01-01

    Cancer is a major health problem in the world. Advances made in cancer therapy have improved the survival of patients in certain types of cancer. However, the overall five-year survival has not significantly improved in the majority of cancer types. Major challenges encountered in having effective cancer therapy are development of drug resistance by the tumor cells, nonspecific cytotoxicity, and inability to affect metastatic tumors by the chemodrugs. Overcoming these challenges requires development and testing of novel therapies. One attractive cancer therapeutic approach is cancer gene therapy. Several laboratories including the authors' laboratory have been investigating nonviral formulations for delivering therapeutic genes as a mode for effective cancer therapy. In this paper the authors will summarize their experience in the development and testing of a cationic lipid-based nanocarrier formulation and the results from their preclinical studies leading to a Phase I clinical trial for nonsmall cell lung cancer. Their nanocarrier formulation containing therapeutic genes such as tumor suppressor genes when administered intravenously effectively controls metastatic tumor growth. Additional Phase I clinical trials based on the results of their nanocarrier formulation have been initiated or proposed for treatment of cancer of the breast, ovary, pancreas, and metastatic melanoma, and will be discussed.

  7. Content-based retrieval of brain tumor in contrast-enhanced MRI images using tumor margin information and learned distance metric.

    Science.gov (United States)

    Yang, Wei; Feng, Qianjin; Yu, Mei; Lu, Zhentai; Gao, Yang; Xu, Yikai; Chen, Wufan

    2012-11-01

    A content-based image retrieval (CBIR) method for T1-weighted contrast-enhanced MRI (CE-MRI) images of brain tumors is presented for diagnosis aid. The method is thoroughly evaluated on a large image dataset. Using the tumor region as a query, the authors' CBIR system attempts to retrieve tumors of the same pathological category. Aside from commonly used features such as intensity, texture, and shape features, the authors use a margin information descriptor (MID), which is capable of describing the characteristics of tissue surrounding a tumor, for representing image contents. In addition, the authors designed a distance metric learning algorithm called Maximum mean average Precision Projection (MPP) to maximize the smooth approximated mean average precision (mAP) to optimize retrieval performance. The effectiveness of MID and MPP algorithms was evaluated using a brain CE-MRI dataset consisting of 3108 2D scans acquired from 235 patients with three categories of brain tumors (meningioma, glioma, and pituitary tumor). By combining MID and other features, the mAP of retrieval increased by more than 6% with the learned distance metrics. The distance metric learned by MPP significantly outperformed the other two existing distance metric learning methods in terms of mAP. The CBIR system using the proposed strategies achieved a mAP of 87.3% and a precision of 89.3% when top 10 images were returned by the system. Compared with scale-invariant feature transform, the MID, which uses the intensity profile as descriptor, achieves better retrieval performance. Incorporating tumor margin information represented by MID with the distance metric learned by the MPP algorithm can substantially improve the retrieval performance for brain tumors in CE-MRI.

  8. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    International Nuclear Information System (INIS)

    Min Yugang; Santhanam, Anand; Ruddy, Bari H; Neelakkantan, Harini; Meeks, Sanford L; Kupelian, Patrick A

    2010-01-01

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  9. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    Energy Technology Data Exchange (ETDEWEB)

    Min Yugang; Santhanam, Anand; Ruddy, Bari H [University of Central Florida, FL (United States); Neelakkantan, Harini; Meeks, Sanford L [M D Anderson Cancer Center Orlando, FL (United States); Kupelian, Patrick A, E-mail: anand.santhanam@orlandohealth.co [Department of Radiation Oncology, University of California, Los Angeles, CA (United States)

    2010-09-07

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  10. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion.

    Science.gov (United States)

    Min, Yugang; Santhanam, Anand; Neelakkantan, Harini; Ruddy, Bari H; Meeks, Sanford L; Kupelian, Patrick A

    2010-09-07

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  11. An efficient entire chaos-based scheme for deniable authentication

    International Nuclear Information System (INIS)

    Xiao Di; Liao Xiaofeng; Wong, K.W.

    2005-01-01

    By using a chaotic encryption-hash parallel algorithm and the semi-group property of Chebyshev chaotic map, we propose a secure and efficient scheme for the deniable authentication. The scheme is efficient, practicable and reliable, with high potential to be adopted for e-commerce

  12. An efficient entire chaos-based scheme for deniable authentication

    Energy Technology Data Exchange (ETDEWEB)

    Xiao Di [College of Computer Science and Engineering, Chongqing University, Chongqing, 400044 (China) and College of Mechanical Engineering, Chongqing University, Chongqing, 400044 (China)]. E-mail: xiaodi_cqu@hotmail.com; Liao Xiaofeng [College of Computer Science and Engineering, Chongqing University, Chongqing, 400044 (China); Wong, K.W. [Department of Computer Engineering and Information Technology, City University of Hong Kong, Hong Kong (China)

    2005-02-01

    By using a chaotic encryption-hash parallel algorithm and the semi-group property of Chebyshev chaotic map, we propose a secure and efficient scheme for the deniable authentication. The scheme is efficient, practicable and reliable, with high potential to be adopted for e-commerce.

  13. First experience with a novel luminescence-based optical sensor for measurement of oxygenation in tumors

    International Nuclear Information System (INIS)

    Jarm, T.; Miklavcic, D.; Lesnicar, H.; Sersa, G.

    2001-01-01

    Background. The purpose of this preliminary study was to evaluate a novel luminescence-based fiber-optic sensor (OxyLite system) for the measurement of partial pressure of oxygen (pO 2 ) in tumors and for the detection of changes in pO 2 as a function of time. The new method was used simultaneously with the laser Doppler flowmetry method for the measurement of relative tissue perfusion. Materials and methods. Blood perfusion and pO 2 were measured continuously via fiber-optic sensors inserted into SA-1 tumors in anesthetized A/J mice. The changes in blood flow and oxygenation of tumors were induced by transient changes of the parameters of anesthesia and by injection of a vasoactive drug hydralazine. Results. Both optical methods used in the study successfully detected the induced changes in blood flow and pO 2 . The measurements of pO 2 were well correlated with measurements of microcirculatory blood perfusion. In the majority of pO 2 measurements, we observed an unexpected behavior of the signal during the stabilization process immediately after the insertion of the probe into tumor. This behaviour of the pO 2 signal was most probably caused by local tissue damage induced by the insertion of the probe. Conclusion. The novel luminescence-based optical oximetry can reliably detect local pO 2 changes in tumors as a function of time but some aspects of prolonged pO 2 measurement by this method require further investigation. (author)

  14. Internal and External Triggering Mechanism of "Smart" Nanoparticle-Based DDSs in Targeted Tumor Therapy.

    Science.gov (United States)

    Qiana, Xian-Ling; Li, Jun; Wei, Ran; Lin, Hui; Xiong, Li-Xia

    2018-05-09

    Anticancer chemotherapeutics have a lot of problems via conventional drug delivery systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: "passive", "active", and "smart" targeting. To summarize the mechanisms of various internal and external "smart" stimulating factors on the basis of findings from in vivo and in vitro studies. A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), "smart" DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. In this review article, we summarize and classify the internal and external triggering mechanism of "smart" nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Geometric accuracy of a novel gimbals based radiation therapy tumor tracking system.

    Science.gov (United States)

    Depuydt, Tom; Verellen, Dirk; Haas, Olivier; Gevaert, Thierry; Linthout, Nadine; Duchateau, Michael; Tournel, Koen; Reynders, Truus; Leysen, Katrien; Hoogeman, Mischa; Storme, Guy; De Ridder, Mark

    2011-03-01

    VERO is a novel platform for image guided stereotactic body radiotherapy. Orthogonal gimbals hold the linac-MLC assembly allowing real-time moving tumor tracking. This study determines the geometric accuracy of the tracking. To determine the tracking error, an 1D moving phantom produced sinusoidal motion with frequencies up to 30 breaths per minute (bpm). Tumor trajectories of patients were reproduced using a 2D robot and pursued with the gimbals tracking system prototype. Using the moving beam light field and a digital-camera-based detection unit tracking errors, system lag and equivalence of pan/tilt performance were measured. The system lag was 47.7 ms for panning and 47.6 ms for tilting. Applying system lag compensation, sinusoidal motion tracking was accurate, with a tracking error 90% percentile E(90%)tracking errors were below 0.14 mm. The 2D tumor trajectories were tracked with an average E(90%) of 0.54 mm, and tracking error standard deviations of 0.20 mm for pan and 0.22 mm for tilt. In terms of dynamic behavior, the gimbaled linac of the VERO system showed to be an excellent approach for providing accurate real-time tumor tracking in radiation therapy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

    International Nuclear Information System (INIS)

    Chen Yang; Shi Luyao; Shu Huazhong; Luo Limin; Coatrieux, Jean-Louis; Yin Xindao; Toumoulin, Christine

    2013-01-01

    In abdomen computed tomography (CT), repeated radiation exposures are often inevitable for cancer patients who receive surgery or radiotherapy guided by CT images. Low-dose scans should thus be considered in order to avoid the harm of accumulative x-ray radiation. This work is aimed at improving abdomen tumor CT images from low-dose scans by using a fast dictionary learning (DL) based processing. Stemming from sparse representation theory, the proposed patch-based DL approach allows effective suppression of both mottled noise and streak artifacts. The experiments carried out on clinical data show that the proposed method brings encouraging improvements in abdomen low-dose CT images with tumors. (paper)

  17. SU-C-207B-03: A Geometrical Constrained Chan-Vese Based Tumor Segmentation Scheme for PET

    International Nuclear Information System (INIS)

    Chen, L; Zhou, Z; Wang, J

    2016-01-01

    Purpose: Accurate segmentation of tumor in PET is challenging when part of tumor is connected with normal organs/tissues with no difference in intensity. Conventional segmentation methods, such as thresholding or region growing, cannot generate satisfactory results in this case. We proposed a geometrical constrained Chan-Vese based scheme to segment tumor in PET for this special case by considering the similarity between two adjacent slices. Methods: The proposed scheme performs segmentation in a slice-by-slice fashion where an accurate segmentation of one slice is used as the guidance for segmentation of rest slices. For a slice that the tumor is not directly connected to organs/tissues with similar intensity values, a conventional clustering-based segmentation method under user’s guidance is used to obtain an exact tumor contour. This is set as the initial contour and the Chan-Vese algorithm is applied for segmenting the tumor in the next adjacent slice by adding constraints of tumor size, position and shape information. This procedure is repeated until the last slice of PET containing tumor. The proposed geometrical constrained Chan-Vese based algorithm was implemented in Matlab and its performance was tested on several cervical cancer patients where cervix and bladder are connected with similar activity values. The positive predictive values (PPV) are calculated to characterize the segmentation accuracy of the proposed scheme. Results: Tumors were accurately segmented by the proposed method even when they are connected with bladder in the image with no difference in intensity. The average PPVs were 0.9571±0.0355 and 0.9894±0.0271 for 17 slices and 11 slices of PET from two patients, respectively. Conclusion: We have developed a new scheme to segment tumor in PET images for the special case that the tumor is quite similar to or connected to normal organs/tissues in the image. The proposed scheme can provide a reliable way for segmenting tumors.

  18. SU-C-207B-03: A Geometrical Constrained Chan-Vese Based Tumor Segmentation Scheme for PET

    Energy Technology Data Exchange (ETDEWEB)

    Chen, L; Zhou, Z; Wang, J [UT Southwestern Medical Center, Dallas, TX (United States)

    2016-06-15

    Purpose: Accurate segmentation of tumor in PET is challenging when part of tumor is connected with normal organs/tissues with no difference in intensity. Conventional segmentation methods, such as thresholding or region growing, cannot generate satisfactory results in this case. We proposed a geometrical constrained Chan-Vese based scheme to segment tumor in PET for this special case by considering the similarity between two adjacent slices. Methods: The proposed scheme performs segmentation in a slice-by-slice fashion where an accurate segmentation of one slice is used as the guidance for segmentation of rest slices. For a slice that the tumor is not directly connected to organs/tissues with similar intensity values, a conventional clustering-based segmentation method under user’s guidance is used to obtain an exact tumor contour. This is set as the initial contour and the Chan-Vese algorithm is applied for segmenting the tumor in the next adjacent slice by adding constraints of tumor size, position and shape information. This procedure is repeated until the last slice of PET containing tumor. The proposed geometrical constrained Chan-Vese based algorithm was implemented in Matlab and its performance was tested on several cervical cancer patients where cervix and bladder are connected with similar activity values. The positive predictive values (PPV) are calculated to characterize the segmentation accuracy of the proposed scheme. Results: Tumors were accurately segmented by the proposed method even when they are connected with bladder in the image with no difference in intensity. The average PPVs were 0.9571±0.0355 and 0.9894±0.0271 for 17 slices and 11 slices of PET from two patients, respectively. Conclusion: We have developed a new scheme to segment tumor in PET images for the special case that the tumor is quite similar to or connected to normal organs/tissues in the image. The proposed scheme can provide a reliable way for segmenting tumors.

  19. Spectral imaging based in vivo model system for characterization of tumor microvessel response to vascular targeting agents

    Science.gov (United States)

    Wankhede, Mamta

    Functional vasculature is vital for tumor growth, proliferation, and metastasis. Many tumor-specific vascular targeting agents (VTAs) aim to destroy this essential tumor vasculature to induce indirect tumor cell death via oxygen and nutrition deprivation. The tumor angiogenesis-inhibiting anti-angiogenics (AIs) and the established tumor vessel targeting vascular disrupting agents (VDAs) are the two major players in the vascular targeting field. Combination of VTAs with conventional therapies or with each other, have been shown to have additive or supra-additive effects on tumor control and treatment. Pathophysiological changes post-VTA treatment in terms of structural and vessel function changes are important parameters to characterize the treatment efficacy. Despite the abundance of information regarding these parameters acquired using various techniques, there remains a need for a quantitative, real-time, and direct observation of these phenomenon in live animals. Through this research we aspired to develop a spectral imaging based mouse tumor system for real-time in vivo microvessel structure and functional measurements for VTA characterization. A model tumor system for window chamber studies was identified, and then combinatorial effects of VDA and AI were characterized in model tumor system. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)

  20. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associated with the utility of MSC-based therapy such as biosafety, immunoprivilege, transfection methods, and distribution in the host. PMID:22530882

  1. Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells

    DEFF Research Database (Denmark)

    Zhang, Wen; Bao, Li; Yang, Shaoxing

    2016-01-01

    Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase......-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5-87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59-100% of 326...

  2. Diagnosis and treatment of pancreatic pseudocysts and cystic tumors based on own material and quoted literature

    Directory of Open Access Journals (Sweden)

    Grzegorz Ćwik

    2013-09-01

    Full Text Available Pseudocysts constitute the most basic cystic lesions of the pancreas. Symptomatic cysts may be treated by means of both minimally invasive methods and surgery. Currently, it is believed that approximately 5% of cystic lesions in the pancreas may in fact, be neoplastic cystic tumors. Their presence is manifested by generally irregular multilocular structures, solid nodules inside the cyst or in the pancreatic duct, frequently vascularized, as well as fragmentary thickening of the cystic wall or septation. Aim: The aim of this paper was to present current management, both diagnostic and therapeutic, in patients with pancreatic pseudocysts and cystic tumors. The article has been written based on the material collected and prepared in the author’s Department as well as on the basis of current reports found in the quoted literature. Material and methods, results: In 2000–2012, the Second Department of General, Gastrointestinal and Oncological Surgery of the Alimentary Tract treated 179 patients with cystic lesions in the region of the pancreas. This group comprised 12 cases of cystic tumors and 167 pseudocysts. Twenty-three patients (13.8% were monitored only and 144 received procedural treatment. Out of the latter group, 75 patients underwent drainage procedures and 48 were qualified to endoscopic cystogastrostomy or cystoduodenostomy. The endoscopic procedure was unsuccessful in 11 cases (23%. In a group of patients with a pancreatic cystic tumor (12 patients, 6 of them (50% underwent therapeutic resection of the tumor with adequate fragment of the gland. Conclusions: Endoscopic drainage is an effective and safe method of minimally invasive treatment of pancreatic cysts. The patients who do not qualify to endoscopic procedures require surgical treatment. The differentiation of a neoplasm from a typical cyst is of fundamental significance for the selection of the treatment method.

  3. Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application

    Science.gov (United States)

    Hao, Yongwei; Wang, Lei; Zhang, Bingxiang; Zhao, Hongjuan; Niu, Mengya; Hu, Yujie; Zheng, Cuixia; Zhang, Hongling; Chang, Junbiao; Zhang, Zhenzhong; Zhang, Yun

    2016-01-01

    It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranostic platform based on degradable manganese dioxide (MnO2) nanosheets. The MnO2 nanosheets with a size of 20-60 nm were first synthesized and modified with (3-Aminopropyl) trimethoxysilane (APTMS) to get amine-functionalized MnO2, and then functionalized by NH2-PEG2000-COOH (PEG). The tumor-targeting group, folic acid (FA), was finally conjugated with the PEGylated MnO2 nanosheets. Then, doxorubicin (DOX), a chemotherapeutic agent, was loaded onto the modified nanosheets through a physical adsorption, which was designated as MnO2-PEG-FA/DOX. The prepared MnO2-PEG-FA/DOX nanosheets with good biocompatibility can not only efficiently deliver DOX to tumor cells in vitro and in vivo, leading to enhanced anti-tumor efficiency, but can also respond to a slightly acidic environment and high concentration of reduced glutathione (GSH), which caused degradation of MnO2 into manganese ions enabling magnetic resonance imaging (MRI). The longitudinal relaxation rate r 1 was 2.26 mM-1 s-1 at pH 5.0 containing 2 mM GSH. These reduction and pH dual-responsive biodegradable nanosheets combining efficient MRI and chemotherapy provide a novel and promising platform for tumor-targeting theranostic application.

  4. Evaluation and comparison of New 4DCT based strategies for proton treatment planning for lung tumors

    International Nuclear Information System (INIS)

    Wang, Ning; Patyal, Baldev; Ghebremedhin, Abiel; Bush, David

    2013-01-01

    To evaluate different strategies for proton lung treatment planning based on four-dimensional CT (4DCT) scans. Twelve cases, involving only gross tumor volumes (GTV), were evaluated. Single image sets of (1) maximum intensity projection (MIP3) of end inhale (EI), middle exhale (ME) and end exhale (EE) images; (2) average intensity projection (AVG) of all phase images; and (3) EE images from 4DCT scans were selected as primary images for proton treatment planning. Internal target volumes (ITVs) outlined by a clinician were imported into MIP3, AVG, and EE images as planning targets. Initially, treatment uncertainties were not included in planning. Each plan was imported into phase images of 4DCT scans. Relative volumes of GTVs covered by 95% of prescribed dose and mean ipsilateral lung dose of a phase image obtained by averaging the dose in inspiration and expiration phases were used to evaluate the quality of a plan for a particular case. For comparing different planning strategies, the mean of the averaged relative volumes of GTVs covered by 95% of prescribed dose and its standard deviation for each planning strategy for all cases were used. Then, treatment uncertainties were included in planning. Each plan was recalculated in phase images of 4DCT scans. Same strategies were used for plan evaluation except dose-volume histograms of the planning target volumes (PTVs) instead of GTVs were used and the mean and standard deviation of the relative volumes of PTVs covered by 95% of prescribed dose and the ipsilateral lung dose were used to compare different planning strategies. MIP3 plans without treatment uncertainties yielded 96.7% of the mean relative GTV covered by 95% of prescribed dose (standard deviations of 5.7% for all cases). With treatment uncertainties, MIP3 plans yielded 99.5% of mean relative PTV covered by 95% of prescribed dose (standard deviations of 0.7%). Inclusion of treatment uncertainties improved PTV dose coverage but also increased the ipsilateral

  5. Real-time tumor motion estimation using respiratory surrogate via memory-based learning

    Science.gov (United States)

    Li, Ruijiang; Lewis, John H.; Berbeco, Ross I.; Xing, Lei

    2012-08-01

    Respiratory tumor motion is a major challenge in radiation therapy for thoracic and abdominal cancers. Effective motion management requires an accurate knowledge of the real-time tumor motion. External respiration monitoring devices (optical, etc) provide a noninvasive, non-ionizing, low-cost and practical approach to obtain the respiratory signal. Due to the highly complex and nonlinear relations between tumor and surrogate motion, its ultimate success hinges on the ability to accurately infer the tumor motion from respiratory surrogates. Given their widespread use in the clinic, such a method is critically needed. We propose to use a powerful memory-based learning method to find the complex relations between tumor motion and respiratory surrogates. The method first stores the training data in memory and then finds relevant data to answer a particular query. Nearby data points are assigned high relevance (or weights) and conversely distant data are assigned low relevance. By fitting relatively simple models to local patches instead of fitting one single global model, it is able to capture highly nonlinear and complex relations between the internal tumor motion and external surrogates accurately. Due to the local nature of weighting functions, the method is inherently robust to outliers in the training data. Moreover, both training and adapting to new data are performed almost instantaneously with memory-based learning, making it suitable for dynamically following variable internal/external relations. We evaluated the method using respiratory motion data from 11 patients. The data set consists of simultaneous measurement of 3D tumor motion and 1D abdominal surface (used as the surrogate signal in this study). There are a total of 171 respiratory traces, with an average peak-to-peak amplitude of ∼15 mm and average duration of ∼115 s per trace. Given only 5 s (roughly one breath) pretreatment training data, the method achieved an average 3D error of 1.5 mm and 95

  6. Real-time tumor motion estimation using respiratory surrogate via memory-based learning

    International Nuclear Information System (INIS)

    Li Ruijiang; Xing Lei; Lewis, John H; Berbeco, Ross I

    2012-01-01

    Respiratory tumor motion is a major challenge in radiation therapy for thoracic and abdominal cancers. Effective motion management requires an accurate knowledge of the real-time tumor motion. External respiration monitoring devices (optical, etc) provide a noninvasive, non-ionizing, low-cost and practical approach to obtain the respiratory signal. Due to the highly complex and nonlinear relations between tumor and surrogate motion, its ultimate success hinges on the ability to accurately infer the tumor motion from respiratory surrogates. Given their widespread use in the clinic, such a method is critically needed. We propose to use a powerful memory-based learning method to find the complex relations between tumor motion and respiratory surrogates. The method first stores the training data in memory and then finds relevant data to answer a particular query. Nearby data points are assigned high relevance (or weights) and conversely distant data are assigned low relevance. By fitting relatively simple models to local patches instead of fitting one single global model, it is able to capture highly nonlinear and complex relations between the internal tumor motion and external surrogates accurately. Due to the local nature of weighting functions, the method is inherently robust to outliers in the training data. Moreover, both training and adapting to new data are performed almost instantaneously with memory-based learning, making it suitable for dynamically following variable internal/external relations. We evaluated the method using respiratory motion data from 11 patients. The data set consists of simultaneous measurement of 3D tumor motion and 1D abdominal surface (used as the surrogate signal in this study). There are a total of 171 respiratory traces, with an average peak-to-peak amplitude of ∼15 mm and average duration of ∼115 s per trace. Given only 5 s (roughly one breath) pretreatment training data, the method achieved an average 3D error of 1.5 mm and 95

  7. Pathway Relevance Ranking for Tumor Samples through Network-Based Data Integration.

    Directory of Open Access Journals (Sweden)

    Lieven P C Verbeke

    Full Text Available The study of cancer, a highly heterogeneous disease with different causes and clinical outcomes, requires a multi-angle approach and the collection of large multi-omics datasets that, ideally, should be analyzed simultaneously. We present a new pathway relevance ranking method that is able to prioritize pathways according to the information contained in any combination of tumor related omics datasets. Key to the method is the conversion of all available data into a single comprehensive network representation containing not only genes but also individual patient samples. Additionally, all data are linked through a network of previously identified molecular interactions. We demonstrate the performance of the new method by applying it to breast and ovarian cancer datasets from The Cancer Genome Atlas. By integrating gene expression, copy number, mutation and methylation data, the method's potential to identify key pathways involved in breast cancer development shared by different molecular subtypes is illustrated. Interestingly, certain pathways were ranked equally important for different subtypes, even when the underlying (epi-genetic disturbances were diverse. Next to prioritizing universally high-scoring pathways, the pathway ranking method was able to identify subtype-specific pathways. Often the score of a pathway could not be motivated by a single mutation, copy number or methylation alteration, but rather by a combination of genetic and epi-genetic disturbances, stressing the need for a network-based data integration approach. The analysis of ovarian tumors, as a function of survival-based subtypes, demonstrated the method's ability to correctly identify key pathways, irrespective of tumor subtype. A differential analysis of survival-based subtypes revealed several pathways with higher importance for the bad-outcome patient group than for the good-outcome patient group. Many of the pathways exhibiting higher importance for the bad

  8. Feasibility of the evidence-based cognitive telerehabilitation program Remind for patients with primary brain tumors.

    Science.gov (United States)

    van der Linden, Sophie D; Sitskoorn, Margriet M; Rutten, Geert-Jan M; Gehring, Karin

    2018-05-01

    Many patients with primary brain tumors experience cognitive deficits. Cognitive rehabilitation programs focus on alleviating these deficits, but availability of such programs is limited. Our large randomized controlled trial (RCT) demonstrated positive effects of the cognitive rehabilitation program developed by our group. We converted the program into the iPad-based cognitive rehabilitation program ReMind, to increase its accessibility. The app incorporates psychoeducation, strategy training and retraining. This pilot study in patients with primary brain tumors evaluates the feasibility of the use of the ReMind-app in a clinical (research) setting in terms of accrual, attrition, adherence and patient satisfaction. The intervention commenced 3 months after resective surgery and patients were advised to spend 3 h per week on the program for 10 weeks. Of 28 eligible patients, 15 patients with presumed low-grade glioma or meningioma provided informed consent. Most important reason for decline was that patients (7) experienced no cognitive complaints. Participants completed on average 71% of the strategy training and 76% of the retraining. Some patients evaluated the retraining as too easy. Overall, 85% of the patients evaluated the intervention as "good" or "excellent". All patients indicated that they would recommend the program to other patients with brain tumors. The ReMind-app is the first evidence-based cognitive telerehabilitation program for adult patients with brain tumors and this pilot study suggests that postoperative cognitive rehabilitation via this app is feasible. Based on patients' feedback, we have expanded the retraining with more difficult exercises. We will evaluate the efficacy of ReMind in an RCT.

  9. Electroporation-based treatment planning for deep-seated tumors based on automatic liver segmentation of MRI images.

    Science.gov (United States)

    Pavliha, Denis; Mušič, Maja M; Serša, Gregor; Miklavčič, Damijan

    2013-01-01

    Electroporation is the phenomenon that occurs when a cell is exposed to a high electric field, which causes transient cell membrane permeabilization. A paramount electroporation-based application is electrochemotherapy, which is performed by delivering high-voltage electric pulses that enable the chemotherapeutic drug to more effectively destroy the tumor cells. Electrochemotherapy can be used for treating deep-seated metastases (e.g. in the liver, bone, brain, soft tissue) using variable-geometry long-needle electrodes. To treat deep-seated tumors, patient-specific treatment planning of the electroporation-based treatment is required. Treatment planning is based on generating a 3D model of the organ and target tissue subject to electroporation (i.e. tumor nodules). The generation of the 3D model is done by segmentation algorithms. We implemented and evaluated three automatic liver segmentation algorithms: region growing, adaptive threshold, and active contours (snakes). The algorithms were optimized using a seven-case dataset manually segmented by the radiologist as a training set, and finally validated using an additional four-case dataset that was previously not included in the optimization dataset. The presented results demonstrate that patient's medical images that were not included in the training set can be successfully segmented using our three algorithms. Besides electroporation-based treatments, these algorithms can be used in applications where automatic liver segmentation is required.

  10. Dosimetric impact of a frame-based strategy in stereotactic radiotherapy of lung tumors

    International Nuclear Information System (INIS)

    Waldeland, Einar; Ramberg, Christina; Arnesen, Marius Roethe; Helland, Aaslaug; Brustugun, Odd Terje; Malinen, Eirik

    2012-01-01

    Introduction. Technological innovations have taken stereotactic body radiotherapy (SBRT) from frame-based strategies to image-guided strategies. In this study, cone beam computed tomography (CBCT) images acquired prior to SBRT of patients with lung tumors was used to study the dosimetric impact of a pure frame-based strategy. Material and methods. Thirty patients with inoperable lung tumors were retrospectively analyzed. All patients had received CBCT-guided SBRT with 3 fractions of 15 Gy to the planning target volume (PTV) margin including immobilization in a stereotactic body frame (SBF). Using the set-up corrections from the co-registration of the CBCT with the planning CT, all individual dose plans were recalculated with an isocenter position equal to the initial set-up position. Dose Volume Histogram (DVH) parameters of the recalculated dose plans were then analyzed. Results. The simulated plans showed that 88% of all fractions resulted in minimum 14.5 Gy to the internal target volume (ITV). For the simulated summed treatment (3 fractions per patient), 83% of the patients would minimum receive the prescription dose (45 Gy) to 100% of the ITV and all except one would receive the prescription dose to more than 90% of the ITV. Conclusions. SBRT including SBF, but without image guidance, results in appropriate dose coverage in most cases, using the current margins. With image guidance, margins for SBRT of lung tumors could possibly be reduced

  11. Lithium and renal and upper urinary tract tumors - results from a nationwide population-based study

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Gerds, Thomas Alexander; Feldt-Rasmussen, Bo

    2015-01-01

    OBJECTIVES: A recent alarming finding suggested an increased risk of renal tumors among long-term lithium users. The objectives of the present study were to estimate rates of renal and upper urinary tract tumors (RUT), malignant and benign, among individuals exposed to successive prescriptions...... for lithium, anticonvulsants, and other psychotropic agents used for bipolar disorder, and among unexposed individuals. METHODS: This was a nationwide, population-based longitudinal study including time-specific data from all individuals exposed to lithium (n = 24,272) or anticonvulsants (n = 386,255), all...... individuals with a diagnosis of bipolar disorder (n = 9,651), and a randomly selected sample of 1,500,000 from the Danish population. The study period was from 1995 to 2012, inclusive. Outcomes were hazard rate ratios (HR) for RUT in three groups: (i) combined malignant and benign, (ii) malignant, and (iii...

  12. Tumor accumulation of {epsilon}-poly-lysines-based polyamines conjugated with boron clusters

    Energy Technology Data Exchange (ETDEWEB)

    Umano, Masayuki; Uechi, Kazuhiro; Uriuda, Takatoshi; Murayama, Sayuri; Azuma, Hideki [Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 5588585 (Japan); Shinohara, Atsuko [Department of Epidemiology and Environmental Health, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 1138421 (Japan); Liu, Young; Ono, Koji [Research Reactor Institute, Kyoto University, 2-1010 Asashiro-nishi, Kumatori 5900494 (Japan); Kirihata, Mitsunori [Department of Bioscience and Informatics, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Sakai 5998531 (Japan); Yanagie, Hironobu [Department of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1138656 (Japan); Nagasaki, Takeshi, E-mail: nagasaki@bioa.eng.osaka-cu.ac.jp [Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 5588585 (Japan)

    2011-12-15

    Boron Neutron Capture Therapy (BNCT) is one of the potent cancer radiotherapies using nuclear reaction between {sup 10}B atoms and the neutron. Whether BNCT will succeed or not depends on tumor selective delivery of {sup 10}B compounds. {epsilon}-Poly-L-lysine is a naturally occurring polyamine characterized by the peptide linkages between the carboxyl and {epsilon}-amino groups of L-lysine. Because of high safety {epsilon}-PLL is applied practically as a food additive due to its strong antimicrobial activity. In this study, we focus on a development of a novel polymeric delivery system for BNCT using biodegradable {epsilon}-PLL conjugated with {sup 10}B-containing clusters (BSH). This polymeric boron carrier will be expected to deliver safely and efficiently into tumor tissues based on Enhanced Permeability and Retention (EPR) effect.

  13. Outcomes of endonasal endoscopic dacryocystorhinostomy after maxillectomy in patients with paranasal sinus and skull base tumors.

    Science.gov (United States)

    Abu-Ghanem, Sara; Ben-Cnaan, Ran; Leibovitch, Igal; Horowitz, Gilad; Fishman, Gadi; Fliss, Dan M; Abergel, Avraham

    2014-06-01

    Maxillectomy followed by radiotherapy and/or chemotherapy can result in lacrimal blockage and the need for subsequent dacryocystorhinostomy (DCR). Endonasal endoscopic DCR, as opposed to external DCR, allows better accuracy and leaves no scar. To date no report was published regarding the results of endoscopic DCR in these patients. The current study presents a retrospective review of all patients with paranasal and skull base tumors who developed nasolacrimal duct blockage after ablative maxillectomy with or without radiotherapy and/or chemotherapy and underwent endonasal endoscopic DCR between January 2006 and October 2012 in a tertiary reference medical center. According to our results, ten patients underwent 11 subsequent endonasal endoscopic DCR. There were 6 men and 4 women with a median age of 55 years (range, 19-81 years); four suffered from benign tumors and six had malignant tumors. All underwent maxillectomy. Six received high-dose radiotherapy. Time interval between primary ablative surgery and endonasal endoscopic DCR was 18 months (range, 7-118 months). Silicone stents were removed after median period of 11 weeks (range, 1-57 weeks). Nine out of ten patients experienced symptomatic improvement following one endonasal endoscopic DCR. One patient had recurrent epiphora and underwent a successful endonasal endoscopic revision DCR. In conclusion, endonasal endoscopic DCR in patients with paranasal and skull base tumors, who previously underwent maxillectomy, is generally successful and not associated with a high rate of complications or failure. Moreover, our findings may suggest that silicone stents can be removed shortly after the operation with high success rate.

  14. Frequency filtering based analysis on the cardiac induced lung tumor motion and its impact on the radiotherapy management

    International Nuclear Information System (INIS)

    Chen, Ting; Qin, Songbing; Xu, Xiaoting; Jabbour, Salma K.; Haffty, Bruce G.; Yue, Ning J.

    2014-01-01

    Purpose/objectives: Lung tumor motion may be impacted by heartbeat in addition to respiration. This study seeks to quantitatively analyze heart-motion-induced tumor motion and to evaluate its impact on lung cancer radiotherapy. Methods/materials: Fluoroscopy images were acquired for 30 lung cancer patients. Tumor, diaphragm, and heart were delineated on selected fluoroscopy frames, and their motion was tracked and converted into temporal signals based on deformable registration propagation. The clinical relevance of heart impact was evaluated using the dose volumetric histogram of the redefined target volumes. Results: Correlation was found between tumor and cardiac motion for 23 patients. The heart-induced motion amplitude ranged from 0.2 to 2.6 mm. The ratio between heart-induced tumor motion and the tumor motion was inversely proportional to the amplitude of overall tumor motion. When the heart motion impact was integrated, there was an average 9% increase in internal target volumes for 17 patients. Dose coverage decrease was observed on redefined planning target volume in simulated SBRT plans. Conclusions: The tumor motion of thoracic cancer patients is influenced by both heart and respiratory motion. The cardiac impact is relatively more significant for tumor with less motion, which may lead to clinically significant uncertainty in radiotherapy for some patients

  15. An off-on fluorescence probe targeting mitochondria based on oxidation-reduction response for tumor cell and tissue imaging

    Science.gov (United States)

    Yao, Hanchun; Cao, Li; Zhao, Weiwei; Zhang, Suge; Zeng, Man; Du, Bin

    2017-10-01

    In this study, a tumor-targeting poly( d, l-lactic-co-glycolic acid) (PLGA) loaded "off-on" fluorescent probe nanoparticle (PFN) delivery system was developed to evaluate the region of tumor by off-on fluorescence. The biodegradability of the nanosize PFN delivery system readily released the probe under tumor acidic conditions. The probe with good biocompatibility was used to monitor the intracellular glutathione (GSH) of cancer cells and selectively localize to mitochondria for tumor imaging. The incorporated tumor-targeting probe was based on the molecular photoinduced electron transfer (PET) mechanism preventing fluorescence ("off" state) and could be easily released under tumor acidic conditions. However, the released tumor-targeting fluorescence probe molecule was selective towards GSH with high selectivity and an ultra-sensitivity for the mitochondria of cancer cells and tissues significantly increasing the probe molecule fluorescence signal ("on" state). The tumor-targeting fluorescence probe showed sensitivity to GSH avoiding interference from cysteine and homocysteine. The PFNs could enable fluorescence-guided cancer imaging during cancer therapy. This work may expand the biological applications of PFNs as a diagnostic reagent, which will be beneficial for fundamental research in tumor imaging. [Figure not available: see fulltext.

  16. Semigroups of transcendental entire functions and their dynamics

    Indian Academy of Sciences (India)

    DINESH KUMAR

    Abstract. We investigate the dynamics of semigroups of transcendental entire func- tions using Fatou–Julia theory. Several results of the dynamics associated with iteration of a transcendental entire function have been extended to transcendental semigroups. We provide some condition for connectivity of the Julia set of the ...

  17. Entire solutions of nonlinear differential-difference equations.

    Science.gov (United States)

    Li, Cuiping; Lü, Feng; Xu, Junfeng

    2016-01-01

    In this paper, we describe the properties of entire solutions of a nonlinear differential-difference equation and a Fermat type equation, and improve several previous theorems greatly. In addition, we also deduce a uniqueness result for an entire function f(z) that shares a set with its shift [Formula: see text], which is a generalization of a result of Liu.

  18. Tumor-stroma metabolic relationship based on lactate shuttle can sustain prostate cancer progression

    International Nuclear Information System (INIS)

    Sanità, Patrizia; Capulli, Mattia; Teti, Anna; Galatioto, Giuseppe Paradiso; Vicentini, Carlo; Chiarugi, Paola; Bologna, Mauro; Angelucci, Adriano

    2014-01-01

    Cancer cell adopts peculiar metabolic strategies aimed to sustain the continuous proliferation in an environment characterized by relevant fluctuations in oxygen and nutrient levels. Monocarboxylate transporters MCT1 and MCT4 can drive such adaptation permitting the transport across plasma membrane of different monocarboxylic acids involved in energy metabolism. Role of MCTs in tumor-stroma metabolic relationship was investigated in vitro and in vivo using transformed prostate epithelial cells, carcinoma cell lines and normal fibroblasts. Moreover prostate tissues from carcinoma and benign hypertrophy cases were analyzed for individuating clinical-pathological implications of MCT1 and MCT4 expression. Transformed prostate epithelial (TPE) and prostate cancer (PCa) cells express both MCT1 and MCT4 and demonstrated variable dependence on aerobic glycolysis for maintaining their proliferative rate. In glucose-restriction the presence of L-lactate determined, after 24 h of treatment, in PCa cells the up-regulation of MCT1 and of cytochrome c oxidase subunit I (COX1), and reduced the activation of AMP-activated protein kinase respect to untreated cells. The blockade of MCT1 function, performed by si RNA silencing, determined an appreciable antiproliferative effect when L-lactate was utilized as energetic fuel. Accordingly L-lactate released by high glycolytic human diploid fibroblasts WI-38 sustained survival and growth of TPE and PCa cells in low glucose culture medium. In parallel, the treatment with conditioned medium from PCa cells was sufficient to induce glycolytic metabolism in WI-38 cells, with upregulation of HIF-1a and MCT4. Co-injection of PCa cells with high glycolytic WI-38 fibroblasts determined an impressive increase in tumor growth rate in a xenograft model that was abrogated by MCT1 silencing in PCa cells. The possible interplay based on L-lactate shuttle between tumor and stroma was confirmed also in human PCa tissue where we observed a positive

  19. SU-F-207-06: CT-Based Assessment of Tumor Volume in Malignant Pleural Mesothelioma

    International Nuclear Information System (INIS)

    Qayyum, F; Armato, S; Straus, C; Husain, A; Vigneswaran, W; Kindler, H

    2015-01-01

    Purpose: To determine the potential utility of computed tomography (CT) scans in the assessment of physical tumor bulk in malignant pleural mesothelioma patients. Methods: Twenty-eight patients with malignant pleural mesothelioma were used for this study. A CT scan was acquired for each patient prior to surgical resection of the tumor (median time between scan and surgery: 27 days). After surgery, the ex-vivo tumor volume was measured by a pathologist using a water displacement method. Separately, a radiologist identified and outlined the tumor boundary on each CT section that demonstrated tumor. These outlines then were analyzed to determine the total volume of disease present, the number of sections with outlines, and the mean volume of disease per outlined section. Subsets of the initial patient cohort were defined based on these parameters, i.e. cases with at least 30 sections of disease with a mean disease volume of at least 3mL per section. For each subset, the R- squared correlation between CT-based tumor volume and physical ex-vivo tumor volume was calculated. Results: The full cohort of 28 patients yielded a modest correlation between CT-based tumor volume and the ex-vivo tumor volume with an R-squared value of 0.66. In general, as the mean tumor volume per section increased, the correlation of CT-based volume with the physical tumor volume improved substantially. For example, when cases with at least 40 CT sections presenting a mean of at least 2mL of disease per section were evaluated (n=20) the R-squared correlation increased to 0.79. Conclusion: While image-based volumetry for mesothelioma may not generally capture physical tumor volume as accurately as one might expect, there exists a set of conditions in which CT-based volume is highly correlated with the physical tumor volume. SGA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology

  20. SU-F-207-06: CT-Based Assessment of Tumor Volume in Malignant Pleural Mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Qayyum, F; Armato, S; Straus, C; Husain, A; Vigneswaran, W; Kindler, H [The University of Chicago, Chicago, IL (United States)

    2015-06-15

    Purpose: To determine the potential utility of computed tomography (CT) scans in the assessment of physical tumor bulk in malignant pleural mesothelioma patients. Methods: Twenty-eight patients with malignant pleural mesothelioma were used for this study. A CT scan was acquired for each patient prior to surgical resection of the tumor (median time between scan and surgery: 27 days). After surgery, the ex-vivo tumor volume was measured by a pathologist using a water displacement method. Separately, a radiologist identified and outlined the tumor boundary on each CT section that demonstrated tumor. These outlines then were analyzed to determine the total volume of disease present, the number of sections with outlines, and the mean volume of disease per outlined section. Subsets of the initial patient cohort were defined based on these parameters, i.e. cases with at least 30 sections of disease with a mean disease volume of at least 3mL per section. For each subset, the R- squared correlation between CT-based tumor volume and physical ex-vivo tumor volume was calculated. Results: The full cohort of 28 patients yielded a modest correlation between CT-based tumor volume and the ex-vivo tumor volume with an R-squared value of 0.66. In general, as the mean tumor volume per section increased, the correlation of CT-based volume with the physical tumor volume improved substantially. For example, when cases with at least 40 CT sections presenting a mean of at least 2mL of disease per section were evaluated (n=20) the R-squared correlation increased to 0.79. Conclusion: While image-based volumetry for mesothelioma may not generally capture physical tumor volume as accurately as one might expect, there exists a set of conditions in which CT-based volume is highly correlated with the physical tumor volume. SGA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology.

  1. Real-time temperature feedback for nanoparticles based tumor thermal treatment (Conference Presentation)

    Science.gov (United States)

    Steinberg, Idan; Tamir, Gil; Gannot, Israel

    2017-02-01

    Systemic hyperthermia therapy exploits the fact that cancer cells are more sensitive to elevated temperatures than healthy tissue. Systemic application of hyperthermia externally usually leads to low efficiency treatment. Recently, our group and others have proposed an antibody conjugated magnetic nanoparticles (MNPs) approach to overcome the limitation of systemic hyperthermia. MNPs can bind specifically to the tumor sites, thus delivering internal highly effective targeted hyperthermia. However, such internal mechanism requires more complicated controls and monitoring. This current work presents a deep tissue temperature monitoring method to control hyperthermia effectiveness and minimize collateral damage to surrounding tissues. A low-frequency narrowband modulation of the RF field used for MNP heating leads to the generation of diffused thermal waves which propagate to the tissue surface and captured by a thermal camera. A Fourier domain, analytical heat transfer model is used for temperature monitoring algorithm. The ill-posed thermal inverse problem is solved efficiently by iterating over the source power until both the amplitude and phase match the recorded thermal image sequence. The narrow bandwidth thermal stimulation enables acquiring deep signals with high SNR. We show that thermal transverse resolution improves as the stimulation frequency increases even slightly above DC, enabling better heat source transverse separation and margin identification in the case of distributed tumors. These results can be used as a part of an overall image and treat system for efficient detection of tumors, manipulation of MNPs and monitoring MNP based hyperthermia.

  2. Segmentation of tumor ultrasound image in HIFU therapy based on texture and boundary encoding

    International Nuclear Information System (INIS)

    Zhang, Dong; Xu, Menglong; Quan, Long; Yang, Yan; Qin, Qianqing; Zhu, Wenbin

    2015-01-01

    It is crucial in high intensity focused ultrasound (HIFU) therapy to detect the tumor precisely with less manual intervention for enhancing the therapy efficiency. Ultrasound image segmentation becomes a difficult task due to signal attenuation, speckle effect and shadows. This paper presents an unsupervised approach based on texture and boundary encoding customized for ultrasound image segmentation in HIFU therapy. The approach oversegments the ultrasound image into some small regions, which are merged by using the principle of minimum description length (MDL) afterwards. Small regions belonging to the same tumor are clustered as they preserve similar texture features. The mergence is completed by obtaining the shortest coding length from encoding textures and boundaries of these regions in the clustering process. The tumor region is finally selected from merged regions by a proposed algorithm without manual interaction. The performance of the method is tested on 50 uterine fibroid ultrasound images from HIFU guiding transducers. The segmentations are compared with manual delineations to verify its feasibility. The quantitative evaluation with HIFU images shows that the mean true positive of the approach is 93.53%, the mean false positive is 4.06%, the mean similarity is 89.92%, the mean norm Hausdorff distance is 3.62% and the mean norm maximum average distance is 0.57%. The experiments validate that the proposed method can achieve favorable segmentation without manual initialization and effectively handle the poor quality of the ultrasound guidance image in HIFU therapy, which indicates that the approach is applicable in HIFU therapy. (paper)

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

    Science.gov (United States)

    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.

  4. Neuropsychological function in adults after high dose fractionated radiation therapy of skull base tumors

    International Nuclear Information System (INIS)

    Glosser, Guila; McManus, Pat; Munzenrider, John; Austin-Seymour, Mary; Fullerton, Barbara; Adams, Judy; Urie, Marcia M.

    1997-01-01

    Purpose: To evaluate the long term effects of high dose fractionated radiation therapy on brain functioning prospectively in adults without primary brain tumors. Methods and Materials: Seventeen patients with histologically confirmed chordomas and low grade chondrosarcomas of the skull base were evaluated with neuropsychological measures of intelligence, language, memory, attention, motor function and mood following surgical resection/biopsy of the tumor prior to irradiation, and then at about 6 months, 2 years and 4 years following completion of treatment. None received chemotherapy. Results: In the patients without tumor recurrence or radiation necrosis, there were no indications of adverse effects on cognitive functioning in the post-acute through the late stages after brain irradiation. Even in patients who received doses of radiation up to 66 Cobalt Gy equivalent through nondiseased (temporal lobe) brain tissue, memory and cognitive functioning remained stable for up to 5 years after treatment. A mild decline in psycho-motor speed was seen in more than half of the patients, and motor slowing was related to higher radiation doses in midline and temporal lobe brain structures. Conclusion: Results suggest that in adults, tolerance for focused radiation is relatively high in cortical brain structures

  5. Deep learning based classification of breast tumors with shear-wave elastography.

    Science.gov (United States)

    Zhang, Qi; Xiao, Yang; Dai, Wei; Suo, Jingfeng; Wang, Congzhi; Shi, Jun; Zheng, Hairong

    2016-12-01

    This study aims to build a deep learning (DL) architecture for automated extraction of learned-from-data image features from the shear-wave elastography (SWE), and to evaluate the DL architecture in differentiation between benign and malignant breast tumors. We construct a two-layer DL architecture for SWE feature extraction, comprised of the point-wise gated Boltzmann machine (PGBM) and the restricted Boltzmann machine (RBM). The PGBM contains task-relevant and task-irrelevant hidden units, and the task-relevant units are connected to the RBM. Experimental evaluation was performed with five-fold cross validation on a set of 227 SWE images, 135 of benign tumors and 92 of malignant tumors, from 121 patients. The features learned with our DL architecture were compared with the statistical features quantifying image intensity and texture. Results showed that the DL features achieved better classification performance with an accuracy of 93.4%, a sensitivity of 88.6%, a specificity of 97.1%, and an area under the receiver operating characteristic curve of 0.947. The DL-based method integrates feature learning with feature selection on SWE. It may be potentially used in clinical computer-aided diagnosis of breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Novel DOTA-based prochelator for divalent peptide vectorization: synthesis of dimeric bombesin analogues for multimodality tumor imaging and therapy.

    Science.gov (United States)

    Abiraj, Keelara; Jaccard, Hugues; Kretzschmar, Martin; Helm, Lothar; Maecke, Helmut R

    2008-07-28

    Dimeric peptidic vectors, obtained by the divalent grafting of bombesin analogues on a newly synthesized DOTA-based prochelator, showed improved qualities as tumor targeted imaging probes in comparison to their monomeric analogues.

  7. In Silico Analysis of Microarray-Based Gene Expression Profiles Predicts Tumor Cell Response to Withanolides

    Directory of Open Access Journals (Sweden)

    Thomas Efferth

    2012-05-01

    Full Text Available Withania somnifera (L. Dunal (Indian ginseng, winter cherry, Solanaceae is widely used in traditional medicine. Roots are either chewed or used to prepare beverages (aqueous decocts. The major secondary metabolites of Withania somnifera are the withanolides, which are C-28-steroidal lactone triterpenoids. Withania somnifera extracts exert chemopreventive and anticancer activities in vitro and in vivo. The aims of the present in silico study were, firstly, to investigate whether tumor cells develop cross-resistance between standard anticancer drugs and withanolides and, secondly, to elucidate the molecular determinants of sensitivity and resistance of tumor cells towards withanolides. Using IC50 concentrations of eight different withanolides (withaferin A, withaferin A diacetate, 3-azerininylwithaferin A, withafastuosin D diacetate, 4-B-hydroxy-withanolide E, isowithanololide E, withafastuosin E, and withaperuvin and 19 established anticancer drugs, we analyzed the cross-resistance profile of 60 tumor cell lines. The cell lines revealed cross-resistance between the eight withanolides. Consistent cross-resistance between withanolides and nitrosoureas (carmustin, lomustin, and semimustin was also observed. Then, we performed transcriptomic microarray-based COMPARE and hierarchical cluster analyses of mRNA expression to identify mRNA expression profiles predicting sensitivity or resistance towards withanolides. Genes from diverse functional groups were significantly associated with response of tumor cells to withaferin A diacetate, e.g. genes functioning in DNA damage and repair, stress response, cell growth regulation, extracellular matrix components, cell adhesion and cell migration, constituents of the ribosome, cytoskeletal organization and regulation, signal transduction, transcription factors, and others.

  8. [Maxillary swing approach in the management of tumors in the central and lateral cranial base].

    Science.gov (United States)

    Liao, Hua; Hua, Qing-quan; Wu, Zhan-yuan

    2006-04-01

    A retrospective review of seventeen patients who were operated through the maxillary swing approach was carried out to assess the efficacy of this approach in the management of tumors of the central and lateral cranial base. From May 2000 to January 2005, 17 patients with primary or recurrent neoplasms involving the central cranial or lateral base underwent surgical resection via maxillary swing approach. Ten patients were male, and other seven patients were female, and age range was 7 to 58 years, with a mean age of 42. 6 years. Eight patients had tumors originally involving lateral cranial base, and nine patients had tumors originated from central cranial base. The pathology spectrum was very wide. Among them, five suffered from chordoma, two had rhabdomyosarcoma, two had squamous cell carcinoma, one had malignant fibrous histiocytoma, one had malignant melanoma, one had esthesioneuroblastoma, one had invaded hypophysoma, two had schwannoma, one had pleomorphic adenoma, and one had angiofibroma. Three patients had received previous surgery, two patients had previous radiation therapy and nine patients received postoperative radiotherapy. Sixteen of all seventeen patients had oncologically complete resection, one had near-total resection. This group patients was followed up from 10 to 60 months, with a median follow-up time of 28 months. Two patients died 14 and 26 months after surgery respectively, as a result of local recurrence and metastasis. One patient defaulted follow-up at 12 months after operation, and the other 14 patients were alive at the time of analysis. Of the 12 malignant tumors, the 1-and 2-year survival rate were 91.67% and 72.92%, respectively. The facial wounds of all patients healed primarily, and there were no necrosis of the maxilla, damage of the temporal branch of the facial nerve, lower-lid ectropion, and facial deformity. Epiphora and facial hypoesthesia were detected in all patients. Four patients (23.5%) developed palatal fistula, ten

  9. Frame-based and frameless stereotactic radiosurgery for intracranial and extracranial tumors

    International Nuclear Information System (INIS)

    Petrovich, Z.; Cheng Yu

    2003-01-01

    During the past 10 years stereotactic frame-based radiosurgery (SRS) emerged as an important treatment modality in the management of selected intracranial lesions. More recently, frameless SRS has extended the potential of ibis treatment to include lesions virtually in any site of the body. Many thousands of patients are being treated annually with frame-based SRS limited to the cranial cavity. A total of 180,222 patients were treated to December 2001 with gamma knife (GK) and, very likely, a similar number was treated with various linear accelerator based SRS systems. Frameless SRS has been performed uncommonly until cyber knife (CK) became available. Over 3,000 patients were treated with CK in the US and Japan. This included patients treated for extracranial lesions. Treatment results in patients treated with GK at University of Southern California (USC) will be presented. From 1994 to 2002, a total of 1,126 patients received GK at USC for various indications. Since metastatic tumor constituted the largest (42.4%) diagnostic category treated, the outcome in this group is specifically discussed. The overall median survival was 9.2 months. The median survival was 8.3, 9.0, 17 and 12 months, for melanoma, lung cancer, breast cancer and renal cell carcinoma, respectively. In multivariate analysis Karnofsky's performance status (70 vs. >70), status of systemic disease (inactive vs. active), tumor histology and total intracranial tumor volume were the only important factors predictive of survival, p=0.0001. Cause of death was found to be due to CNS problems in about 25% of patients with a diagnosis other than melanoma, while it was 42% in those with melanoma. GK SRS was given on an outpatient basis and was very well tolerated by the patients. Symptomatic focal radionecrosis requiring craniotomy for its removal was noted in <5% of patients. An excellent palliative benefit was obtained in nearly all patients. The treatment was compatible with a good quality of life

  10. Temporalis myofascial flap for primary cranial base reconstruction after tumor resection.

    Science.gov (United States)

    Eldaly, Ahmed; Magdy, Emad A; Nour, Yasser A; Gaafar, Alaa H

    2008-07-01

    To evaluate the use of the temporalis myofascial flap in primary cranial base reconstruction following surgical tumor ablation and to explain technical issues, potential complications, and donor site consequences along with their management. Retrospective case series. Tertiary referral center. Forty-one consecutive patients receiving primary temporalis myofascial flap reconstructions following cranial base tumor resections in a 4-year period. Flap survival, postoperative complications, and donor site morbidity. Patients included 37 males and 4 females ranging in age from 10 to 65 years. Two patients received preoperative and 18 postoperative radiation therapy. Patient follow-up ranged from 4 to 39 months. The whole temporalis muscle was used in 26 patients (63.4%) and only part of a coronally split muscle was used in 15 patients (36.6%). Nine patients had primary donor site reconstruction using a Medpor((R)) (Porex Surgical, Inc., Newnan, GA) temporal fossa implant; these had excellent aesthetic results. There were no cases of complete flap loss. Partial flap dehiscence was seen in six patients (14.6%); only two required surgical débridement. None of the patients developed cerebrospinal leaks or meningitis. One patient was left with complete paralysis of the temporal branch of the facial nerve. Three patients (all had received postoperative irradiation) developed permanent trismus. The temporalis myofascial flap was found to be an excellent reconstructive alternative for a wide variety of skull base defects following tumor ablation. It is a very reliable, versatile flap that is usually available in the operative field with relatively low donor site aesthetic and functional morbidity.

  11. TH-E-17A-10: Markerless Lung Tumor Tracking Based On Beams Eye View EPID Images

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, T; Kearney, V; Liu, H; Jiang, L; Foster, R; Mao, W [UT Southwestern Medical Center, Dallas, Texas (United States); Rozario, T; Bereg, S [University of Texas at Dallas, Richardson, Texas (United States); Klash, S [Premier Cancer Centers, Dallas, TX (United States)

    2014-06-15

    Purpose: Dynamic tumor tracking or motion compensation techniques have proposed to modify beam delivery following lung tumor motion on the flight. Conventional treatment plan QA could be performed in advance since every delivery may be different. Markerless lung tumor tracking using beams eye view EPID images provides a best treatment evaluation mechanism. The purpose of this study is to improve the accuracy of the online markerless lung tumor motion tracking method. Methods: The lung tumor could be located on every frame of MV images during radiation therapy treatment by comparing with corresponding digitally reconstructed radiograph (DRR). A kV-MV CT corresponding curve is applied on planning kV CT to generate MV CT images for patients in order to enhance the similarity between DRRs and MV treatment images. This kV-MV CT corresponding curve was obtained by scanning a same CT electron density phantom by a kV CT scanner and MV scanner (Tomotherapy) or MV CBCT. Two sets of MV DRRs were then generated for tumor and anatomy without tumor as the references to tracking the tumor on beams eye view EPID images. Results: Phantom studies were performed on a Varian TrueBeam linac. MV treatment images were acquired continuously during each treatment beam delivery at 12 gantry angles by iTools. Markerless tumor tracking was applied with DRRs generated from simulated MVCT. Tumors were tracked on every frame of images and compared with expected positions based on programed phantom motion. It was found that the average tracking error were 2.3 mm. Conclusion: This algorithm is capable of detecting lung tumors at complicated environment without implanting markers. It should be noted that the CT data has a slice thickness of 3 mm. This shows the statistical accuracy is better than the spatial accuracy. This project has been supported by a Varian Research Grant.

  12. Esophagus sparing with IMRT in lung tumor irradiation: An EUD-based optimization technique

    International Nuclear Information System (INIS)

    Chapet, Olivier; Thomas, Emma; Kessler, Marc L.; Fraass, Benedick A.; Ten Haken, Randall K.

    2005-01-01

    Purpose: The aim of this study was to evaluate (1) the use of generalized equivalent uniform dose (gEUD) to optimize dose escalation of lung tumors when the esophagus overlaps the planning target volume (PTV) and (2) the potential benefit of further dose escalation in only the part of the PTV that does not overlap the esophagus. Methods and Materials: The treatment-planning computed tomography (CT) scans of patients with primary lung tumors located in different regions of the left and right lung were used for the optimization of beamlet intensity modulated radiation therapy (IMRT) plans. In all cases, the PTV overlapped part of the esophagus. The dose in the PTV was maximized according to 7 different primary cost functions: 2 plans that made use of mean dose (MD) (the reference plan, in which the 95% isodose surface covered the PTV and a second plan that had no constraint on the minimum isodose), 3 plans based on maximizing gEUD for the whole PTV with ever increasing assumptions for tumor aggressiveness, and 2 plans that used different gEUD values in 2 simultaneous, overlapping target volumes (the whole PTV and the PTV minus esophagus). Beam arrangements and NTCP-based costlets for the organs at risk (OARs) were kept identical to the original conformal plan for each case. Regardless of optimization method, the relative ranking of the resulting plans was evaluated in terms of the absence of cold spots within the PTV and the final gEUD computed for the whole PTV. Results: Because the MD-optimized plans lacked a constraint on minimum PTV coverage, they resulted in cold spots that affected approximately 5% of the PTV volume. When optimizing over the whole PTV volume, gEUD-optimized plans resulted in higher equivalent uniform PTV doses than did the reference plan while still maintaining normal-tissue constraints. However, only under the assumption of extremely aggressive tumors could cold spots in the PTV be avoided. Generally, high-level overall results are obtained

  13. PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice

    DEFF Research Database (Denmark)

    Huda, Pie; Binderup, Tina; Pedersen, Martin Cramer

    2015-01-01

    64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model...... radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold....

  14. Acute Metabolic Alkalosis Enhances Response of C3H Mouse Mammary Tumors to the Weak Base Mitoxantrone

    Directory of Open Access Journals (Sweden)

    Natarajan Raghunand

    2001-01-01

    Full Text Available Uptake of weak acid and weak base chemotherapeutic drugs by tumors is greatly influenced by the tumor extracellular/interstitial pH (pHe, the intracellular pH (pHi maintained by the tumor cells, and by the ionization properties of the drug itself. The acid-outside plasmalemmal pH gradient in tumors acts to exclude weak base drugs like the anthracyclines, anthraquinones, and vinca alkaloids from the cells, leading to a substantial degree of “physiological drug resistance” in tumors. We have induced acute metabolic alkalosis in C3H tumor-bearing C3H/hen mice, by gavage and by intraperitoneal (i.p. administration of NaHCO3. 31P magnetic resonance spectroscopic measurements of 3-aminopropylphosphonate show increases of up to 0.6 pH units in tumor pHe, and 0.2 to 0.3 pH units in hind leg tissue pHe, within 2 hours of i.p. administration of NaHCO3. Theoretical calculations of mitoxantrone uptake into tumor and normal (hind leg tissue at the measured pH, and pHI values indicate that a gain in therapeutic index of up to 3.3-fold is possible with NaHCO3 pretreatment. Treatment of C3H tumor-bearing mice with 12 mg/kg mitoxantrone resulted in a tumor growth delay of 9 days, whereas combined NaHCO3mitoxantrone therapy resulted in an enhancement of the TGD to 16 days.

  15. Subtype differentiation of renal tumors using voxel-based histogram analysis of intravoxel incoherent motion parameters.

    Science.gov (United States)

    Gaing, Byron; Sigmund, Eric E; Huang, William C; Babb, James S; Parikh, Nainesh S; Stoffel, David; Chandarana, Hersh

    2015-03-01

    The aim of this study was to determine if voxel-based histogram analysis of intravoxel incoherent motion imaging (IVIM) parameters can differentiate various subtypes of renal tumors, including benign and malignant lesions. A total of 44 patients with renal tumors who underwent surgery and had histopathology available were included in this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved, single-institution prospective study. In addition to routine renal magnetic resonance imaging examination performed on a 1.5-T system, all patients were imaged with axial diffusion-weighted imaging using 8 b values (range, 0-800 s/mm). A biexponential model was fitted to the diffusion signal data using a segmented algorithm to extract the IVIM parameters perfusion fraction (fp), tissue diffusivity (Dt), and pseudodiffusivity (Dp) for each voxel. Mean and histogram measures of heterogeneity (standard deviation, skewness, and kurtosis) of IVIM parameters were correlated with pathology results of tumor subtype using unequal variance t tests to compare subtypes in terms of each measure. Correction for multiple comparisons was accomplished using the Tukey honestly significant difference procedure. A total of 44 renal tumors including 23 clear cell (ccRCC), 4 papillary (pRCC), 5 chromophobe, and 5 cystic renal cell carcinomas, as well as benign lesions, 4 oncocytomas (Onc) and 3 angiomyolipomas (AMLs), were included in our analysis. Mean IVIM parameters fp and Dt differentiated 8 of 15 pairs of renal tumors. Histogram analysis of IVIM parameters differentiated 9 of 15 subtype pairs. One subtype pair (ccRCC vs pRCC) was differentiated by mean analysis but not by histogram analysis. However, 2 other subtype pairs (AML vs Onc and ccRCC vs Onc) were differentiated by histogram distribution parameters exclusively. The standard deviation of Dt [σ(Dt)] differentiated ccRCC (0.362 ± 0.136 × 10 mm/s) from AML (0.199 ± 0.043 × 10 mm/s) (P = 0

  16. Entire solutions of Fermat type q-difference differential equations

    Directory of Open Access Journals (Sweden)

    Kai Liu

    2013-02-01

    Full Text Available In this article, we describe the finite-order transcendental entire solutions of Fermat type $q$-difference and $q$-difference differential equations. In addition, we investigate the similarities and other properties among those solutions.

  17. A state-based probabilistic model for tumor respiratory motion prediction

    International Nuclear Information System (INIS)

    Kalet, Alan; Sandison, George; Schmitz, Ruth; Wu Huanmei

    2010-01-01

    This work proposes a new probabilistic mathematical model for predicting tumor motion and position based on a finite state representation using the natural breathing states of exhale, inhale and end of exhale. Tumor motion was broken down into linear breathing states and sequences of states. Breathing state sequences and the observables representing those sequences were analyzed using a hidden Markov model (HMM) to predict the future sequences and new observables. Velocities and other parameters were clustered using a k-means clustering algorithm to associate each state with a set of observables such that a prediction of state also enables a prediction of tumor velocity. A time average model with predictions based on average past state lengths was also computed. State sequences which are known a priori to fit the data were fed into the HMM algorithm to set a theoretical limit of the predictive power of the model. The effectiveness of the presented probabilistic model has been evaluated for gated radiation therapy based on previously tracked tumor motion in four lung cancer patients. Positional prediction accuracy is compared with actual position in terms of the overall RMS errors. Various system delays, ranging from 33 to 1000 ms, were tested. Previous studies have shown duty cycles for latencies of 33 and 200 ms at around 90% and 80%, respectively, for linear, no prediction, Kalman filter and ANN methods as averaged over multiple patients. At 1000 ms, the previously reported duty cycles range from approximately 62% (ANN) down to 34% (no prediction). Average duty cycle for the HMM method was found to be 100% and 91 ± 3% for 33 and 200 ms latency and around 40% for 1000 ms latency in three out of four breathing motion traces. RMS errors were found to be lower than linear and no prediction methods at latencies of 1000 ms. The results show that for system latencies longer than 400 ms, the time average HMM prediction outperforms linear, no prediction, and the more

  18. Building a high-resolution T2-weighted MR-based probabilistic model of tumor occurrence in the prostate.

    Science.gov (United States)

    Nagarajan, Mahesh B; Raman, Steven S; Lo, Pechin; Lin, Wei-Chan; Khoshnoodi, Pooria; Sayre, James W; Ramakrishna, Bharath; Ahuja, Preeti; Huang, Jiaoti; Margolis, Daniel J A; Lu, David S K; Reiter, Robert E; Goldin, Jonathan G; Brown, Matthew S; Enzmann, Dieter R

    2018-02-19

    We present a method for generating a T2 MR-based probabilistic model of tumor occurrence in the prostate to guide the selection of anatomical sites for targeted biopsies and serve as a diagnostic tool to aid radiological evaluation of prostate cancer. In our study, the prostate and any radiological findings within were segmented retrospectively on 3D T2-weighted MR images of 266 subjects who underwent radical prostatectomy. Subsequent histopathological analysis determined both the ground truth and the Gleason grade of the tumors. A randomly chosen subset of 19 subjects was used to generate a multi-subject-derived prostate template. Subsequently, a cascading registration algorithm involving both affine and non-rigid B-spline transforms was used to register the prostate of every subject to the template. Corresponding transformation of radiological findings yielded a population-based probabilistic model of tumor occurrence. The quality of our probabilistic model building approach was statistically evaluated by measuring the proportion of correct placements of tumors in the prostate template, i.e., the number of tumors that maintained their anatomical location within the prostate after their transformation into the prostate template space. Probabilistic model built with tumors deemed clinically significant demonstrated a heterogeneous distribution of tumors, with higher likelihood of tumor occurrence at the mid-gland anterior transition zone and the base-to-mid-gland posterior peripheral zones. Of 250 MR lesions analyzed, 248 maintained their original anatomical location with respect to the prostate zones after transformation to the prostate. We present a robust method for generating a probabilistic model of tumor occurrence in the prostate that could aid clinical decision making, such as selection of anatomical sites for MR-guided prostate biopsies.

  19. Parameter estimation of brain tumors using intraoperative thermal imaging based on artificial tactile sensing in conjunction with artificial neural network

    International Nuclear Information System (INIS)

    Sadeghi-Goughari, M; Mojra, A; Sadeghi, S

    2016-01-01

    Intraoperative Thermal Imaging (ITI) is a new minimally invasive diagnosis technique that can potentially locate margins of brain tumor in order to achieve maximum tumor resection with least morbidity. This study introduces a new approach to ITI based on artificial tactile sensing (ATS) technology in conjunction with artificial neural networks (ANN) and feasibility and applicability of this method in diagnosis and localization of brain tumors is investigated. In order to analyze validity and reliability of the proposed method, two simulations were performed. (i) An in vitro experimental setup was designed and fabricated using a resistance heater embedded in agar tissue phantom in order to simulate heat generation by a tumor in the brain tissue; and (ii) A case report patient with parafalcine meningioma was presented to simulate ITI in the neurosurgical procedure. In the case report, both brain and tumor geometries were constructed from MRI data and tumor temperature and depth of location were estimated. For experimental tests, a novel assisted surgery robot was developed to palpate the tissue phantom surface to measure temperature variations and ANN was trained to estimate the simulated tumor’s power and depth. Results affirm that ITI based ATS is a non-invasive method which can be useful to detect, localize and characterize brain tumors. (paper)

  20. The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines.

    Science.gov (United States)

    Nishida, Toshirou; Blay, Jean-Yves; Hirota, Seiichi; Kitagawa, Yuko; Kang, Yoon-Koo

    2016-01-01

    Although gastrointestinal stromal tumors (GISTs) are a rare type of cancer, they are the commonest sarcoma in the gastrointestinal tract. Molecularly targeted therapy, such as imatinib therapy, has revolutionized the treatment of advanced GIST and facilitates scientific research on GIST. Nevertheless, surgery remains a mainstay of treatment to obtain a permanent cure for GIST even in the era of targeted therapy. Many GIST guidelines have been published to guide the diagnosis and treatment of the disease. We review current versions of GIST guidelines published by the National Comprehensive Cancer Network, by the European Society for Medical Oncology, and in Japan. All clinical practice guidelines for GIST include recommendations based on evidence as well as on expert consensus. Most of the content is very similar, as represented by the following examples: GIST is a heterogeneous disease that may have mutations in KIT, PDGFRA, HRAS, NRAS, BRAF, NF1, or the succinate dehydrogenase complex, and these subsets of tumors have several distinctive features. Although there are some minor differences among the guidelines--for example, in the dose of imatinib recommended for exon 9-mutated GIST or the efficacy of antigen retrieval via immunohistochemistry--their common objectives regarding diagnosis and treatment are not only to improve the diagnosis of GIST and the prognosis of patients but also to control medical costs. This review describes the current standard diagnosis, treatment, and follow-up of GISTs based on the recommendations of several guidelines and expert consensus.

  1. Patterns of failure following treatment for medulloblastoma: is it necessary to treat the entire posterior fossa?

    International Nuclear Information System (INIS)

    Fukunaga-Johnson, Nina; Lee, Jason H.; Robertson, Patricia; Sandler, Howard M.; McNeil, Elizabeth; Goldwein, Joel W.

    1997-01-01

    Purpose: Craniospinal radiation (CSRT) followed by a boost to the entire posterior fossa (PF) is standard post-operative therapy for patients with medulloblastoma. A large proportion of recurrences after treatment are local with approximately 50-70% of recurrences occurring in the PF. It is unclear, however, whether these failures are occurring in the original tumor bed, or outside the tumor bed but still within the PF. With improved diagnostic imaging, better definition of tumor volumes, and the use of 3D conformal therapy, we may be able to restrict the boost volume to the tumor bed plus a margin without compromising local control. This retrospective study analyzes the patterns of failure within the PF of a series of patients treated with radiation therapy (RT). Methods: From (7(86)) through (2(96)), 27 of 114 (24%) patients > 18 mo and < 18 yr with medulloblastoma, who were treated at the University of Michigan and Children's Hospital of Philadelphia, with RT following surgical resection were found to have a recurrence. RT consisted of CSRT followed by a boost to the entire posterior fossa. Patient's preoperative MRI and/or CT studies were used to compare the original tumor volume with the specific region of local relapse. Failure was defined as MRI or CT evidence of recurrence or positive cerebrospinal fluid cytology. Relapse was scored as local, if it was within the original tumor bed and regional, if it was outside of the tumor bed but still within the PF. Results: The median age of the patients was 8.6 years. Three patients were < 3 years old. (21(27)) had disease localized to the PF. (19(21)) patients received chemotherapy during their treatment regimen; 6 patients did not have information on systemic treatment. The median dose of RT to the craniospinal axis was 32.5 Gy and to the PF was 55.2 Gy. The median time to recurrence was 19.5 months. Local failure within the tumor bed as any component of first failure occurred in 52% ((14(27))) of all failures but

  2. Neurophysiological Identification of Cranial Nerves During Endoscopic Endonasal Surgery of Skull Base Tumors: Pilot Study Technical Report.

    Science.gov (United States)

    Shkarubo, Alexey Nikolaevich; Chernov, Ilia Valerievich; Ogurtsova, Anna Anatolievna; Moshchev, Dmitry Aleksandrovich; Lubnin, Andrew Jurievich; Andreev, Dmitry Nicolaevich; Koval, Konstantin Vladimirovich

    2017-02-01

    Intraoperative identification of cranial nerves is crucial for safe surgery of skull base tumors. Currently, only a small number of published papers describe the technique of trigger electromyography (t-EMG) in endoscopic endonasal removal of such tumors. To assess the effectiveness of t-EMG in preventing intraoperative cranial nerve damage in endoscopic endonasal surgery of skull base tumors. Nine patients were operated on using the endoscopic endonasal approach within a 1-year period. The tumors included large skull base chordomas and trigeminal neurinomas localized in the cavernous sinus. During the surgical process, cranial nerve identification was carried out using monopolar and bipolar t-EMG methods. Assessment of cranial nerve functional activity was conducted both before and after tumor removal. We mapped 17 nerves in 9 patients. Third, fifth, and sixth cranial nerves were identified intraoperatively. There were no cases of postoperative functional impairment of the mapped cranial nerves. In one case we were unable to get an intraoperative response from the fourth cranial nerve and observed its postoperative transient plegia (the function was normal before surgery). t-EMG allows surgeons to control the safety of cranial nerves both during and after skull base tumor removal. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Novel Therapeutic Strategies for Solid Tumor Based on Body's Intrinsic Antitumor Immune System.

    Science.gov (United States)

    Duan, Haifeng

    2018-05-22

    The accumulation of mutated somatic cells due to the incompetency of body's immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor-targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumor-targeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloid-derived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body's internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly. © 2018 The Author(s). Published by S. Karger AG, Basel.

  4. Technical Note: A deep learning-based autosegmentation of rectal tumors in MR images.

    Science.gov (United States)

    Wang, Jiazhou; Lu, Jiayu; Qin, Gan; Shen, Lijun; Sun, Yiqun; Ying, Hongmei; Zhang, Zhen; Hu, Weigang

    2018-04-16

    Manual contouring of gross tumor volumes (GTV) is a crucial and time-consuming process in rectum cancer radiotherapy. This study aims to develop a simple deep learning-based autosegmentation algorithm to segment rectal tumors on T2-weighted MR images. MRI scans (3T, T2-weighted) of 93 patients with locally advanced (cT3-4 and/or cN1-2) rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were enrolled in this study. A 2D U-net similar network was established as a training model. The model was trained in two phases to increase efficiency. These phases were tumor recognition and tumor segmentation. An opening (erosion and dilation) process was implemented to smooth contours after segmentation. Data were randomly separated into training (90%) and validation (10%) datasets for a 10-folder cross-validation. Additionally, 20 patients were double contoured for performance evaluation. Four indices were calculated to evaluate the similarity of automated and manual segmentation, including Hausdorff distance (HD), average surface distance (ASD), Dice index (DSC), and Jaccard index (JSC). The DSC, JSC, HD, and ASD (mean ± SD) were 0.74 ± 0.14, 0.60 ± 0.16, 20.44 ± 13.35, and 3.25 ± 1.69 mm for validation dataset; and these indices were 0.71 ± 0.13, 0.57 ± 0.15, 14.91 ± 7.62, and 2.67 ± 1.46 mm between two human radiation oncologists, respectively. No significant difference has been observed between automated segmentation and manual segmentation considering DSC (P = 0.42), JSC (P = 0.35), HD (P = 0.079), and ASD (P = 0.16). However, significant difference was found for HD (P = 0.0027) without opening process. This study showed that a simple deep learning neural network can perform segmentation for rectum cancer based on MRI T2 images with results comparable to a human. © 2018 American Association of Physicists in Medicine.

  5. Dose painting based on tumor uptake of Cu-ATSM and FDG: a comparative study

    International Nuclear Information System (INIS)

    Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael; Hollensen, Christian; Pommer, Tobias; Munck af Rosenschöld, Per; Kristensen, Annemarie Thuri; Kjær, Andreas; McEvoy, Fintan J; Engelholm, Svend Aage

    2014-01-01

    Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The purpose of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[ 18 F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N 4 )-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models. Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and 64 Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes for dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were formed in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions for each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with construction of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients. Comparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. 64 Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions. Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, 64 Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64 Cu-ATSM at two

  6. Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

    Directory of Open Access Journals (Sweden)

    Hui Guo

    2016-07-01

    Full Text Available Evodiamine (EVO and rutaecarpine (RUT are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.

  7. Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors

    International Nuclear Information System (INIS)

    Zamenhof, R.G.; Clement, S.D.; Harling, O.K.; Brenner, J.F.; Wazer, D.E.; Madoc-Jones, H.; Yanch, J.C.

    1990-01-01

    Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction

  8. Assessment of Canine Mast Cell Tumor Mortality Risk Based on Clinical, Histologic, Immunohistochemical, and Molecular Features.

    Science.gov (United States)

    Horta, Rodrigo S; Lavalle, Gleidice E; Monteiro, Lidianne N; Souza, Mayara C C; Cassali, Geovanni D; Araújo, Roberto B

    2018-03-01

    Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is heterogeneous in clinical presentation and biological behavior, with a variable potential for recurrence and metastasis. Accurate prediction of clinical outcomes has been challenging. The study objective was to develop a system for classification of canine MCT according to the mortality risk based on individual assessment of clinical, histologic, immunohistochemical, and molecular features. The study included 149 dogs with a histologic diagnosis of cutaneous or subcutaneous MCT. By univariate analysis, MCT metastasis and related death was significantly associated with clinical stage ( P < .0001, r P = -0.610), history of tumor recurrence ( P < .0001, r P = -0.550), Patnaik ( P < .0001, r P = -0.380) and Kiupel grades ( P < .0001, r P = -0.500), predominant organization of neoplastic cells ( P < .0001, r P = -0.452), mitotic count ( P < .0001, r P = -0.325), Ki-67 labeling index ( P < .0001, r P = -0.414), KITr pattern ( P = .02, r P = 0.207), and c-KIT mutational status ( P < .0001, r P = -0.356). By multivariate analysis with Cox proportional hazard model, only 2 features were independent predictors of overall survival: an amendment of the World Health Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481]; P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158-23.268]; P < .001]. From these results, we propose an amendment of the WHO staging system, a method of risk analysis, and a suggested approach to clinical and laboratory evaluation of dogs with cutaneous MCT.

  9. First Application of 7T Magnetic Resonance Imaging in Endoscopic Endonasal Surgery of Skull Base Tumors

    Science.gov (United States)

    Barrett, Thomas F; Dyvorne, Hadrien A; Padormo, Francesco; Pawha, Puneet S; Delman, Bradley N; Shrivastava, Raj K; Balchandani, Priti

    2018-01-01

    Background Successful endoscopic endonasal surgery for the resection of skull base tumors is reliant on preoperative imaging to delineate pathology from the surrounding anatomy. The increased signal-to-noise ratio afforded by 7T MRI can be used to increase spatial and contrast resolution, which may lend itself to improved imaging of skull base. In this study, we apply a 7T imaging protocol to patients with skull base tumors and compare the images to clinical standard of care. Methods Images were acquired at 7T on 11 patients with skull base lesions. Two neuroradiologists evaluated clinical 1.5T, 3T, and 7T scans for detection of intracavernous cranial nerves and ICA branches. Detection rates were compared. Images were utilized for surgical planning and uploaded to a neuronavigation platform and used to guide surgery. Results Image analysis yielded improved detection rates of cranial nerves and ICA branches at 7T. 7T images were successfully incorporated into preoperative planning and intraoperative neuronavigation. Conclusion Our study represents the first application of 7T MRI to the full neurosurgical workflow for endoscopic endonasal surgery. We detected higher rates of cranial nerves and ICA branches at 7T MRI compared to 3T and 1.5 T, and found that integration of 7T into surgical planning and guidance was feasible. These results suggest a potential for 7T MRI to reduce surgical complications. Future studies comparing standardized 7T, 3T, and 1.5 T MRI protocols in a larger number of patients are warranted to determine the relative benefit of 7T MRI for endonasal endoscopic surgical efficacy. PMID:28359922

  10. First Application of 7-T Magnetic Resonance Imaging in Endoscopic Endonasal Surgery of Skull Base Tumors.

    Science.gov (United States)

    Barrett, Thomas F; Dyvorne, Hadrien A; Padormo, Francesco; Pawha, Puneet S; Delman, Bradley N; Shrivastava, Raj K; Balchandani, Priti

    2017-07-01

    Successful endoscopic endonasal surgery for the resection of skull base tumors is reliant on preoperative imaging to delineate pathology from the surrounding anatomy. The increased signal-to-noise ratio afforded by 7-T MRI can be used to increase spatial and contrast resolution, which may lend itself to improved imaging of the skull base. In this study, we apply a 7-T imaging protocol to patients with skull base tumors and compare the images with clinical standard of care. Images were acquired at 7 T on 11 patients with skull base lesions. Two neuroradiologists evaluated clinical 1.5-, 3-, and 7-T scans for detection of intracavernous cranial nerves and internal carotid artery (ICA) branches. Detection rates were compared. Images were used for surgical planning and uploaded to a neuronavigation platform and used to guide surgery. Image analysis yielded improved detection rates of cranial nerves and ICA branches at 7 T. The 7-T images were successfully incorporated into preoperative planning and intraoperative neuronavigation. Our study represents the first application of 7-T MRI to the full neurosurgical workflow for endoscopic endonasal surgery. We detected higher rates of cranial nerves and ICA branches at 7-T MRI compared with 3- and 1.5-T MRI, and found that integration of 7 T into surgical planning and guidance was feasible. These results suggest a potential for 7-T MRI to reduce surgical complications. Future studies comparing standardized 7-, 3-, and 1.5-T MRI protocols in a larger number of patients are warranted to determine the relative benefit of 7-T MRI for endonasal endoscopic surgical efficacy. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. A simple method for detecting tumor in T2-weighted MRI brain images. An image-based analysis

    International Nuclear Information System (INIS)

    Lau, Phooi-Yee; Ozawa, Shinji

    2006-01-01

    The objective of this paper is to present a decision support system which uses a computer-based procedure to detect tumor blocks or lesions in digitized medical images. The authors developed a simple method with a low computation effort to detect tumors on T2-weighted Magnetic Resonance Imaging (MRI) brain images, focusing on the connection between the spatial pixel value and tumor properties from four different perspectives: cases having minuscule differences between two images using a fixed block-based method, tumor shape and size using the edge and binary images, tumor properties based on texture values using spatial pixel intensity distribution controlled by a global discriminate value, and the occurrence of content-specific tumor pixel for threshold images. Measurements of the following medical datasets were performed: different time interval images, and different brain disease images on single and multiple slice images. Experimental results have revealed that our proposed technique incurred an overall error smaller than those in other proposed methods. In particular, the proposed method allowed decrements of false alarm and missed alarm errors, which demonstrate the effectiveness of our proposed technique. In this paper, we also present a prototype system, known as PCB, to evaluate the performance of the proposed methods by actual experiments, comparing the detection accuracy and system performance. (author)

  12. A polymer-based magnetic resonance tracer for visualization of solid tumors by 13C spectroscopic imaging.

    Directory of Open Access Journals (Sweden)

    Yoshikazu Suzuki

    Full Text Available Morphological imaging precedes lesion-specific visualization in magnetic resonance imaging (MRI because of the superior ability of this technique to depict tissue morphology with excellent spatial and temporal resolutions. To achieve lesion-specific visualization of tumors by MRI, we investigated the availability of a novel polymer-based tracer. Although the 13C nucleus is a candidate for a detection nucleus because of its low background signal in the body, the low magnetic resonance sensitivity of the nucleus needs to be resolved before developing a 13C-based tracer. In order to overcome this problem, we enriched polyethylene glycol (PEG, a biocompatible polymer, with 13C atoms. 13C-PEG40,000 (13C-PEG with an average molecular weight of 40 kDa emitted a single 13C signal with a high signal-to-noise ratio due to its ability to maintain signal sharpness, as was confirmed by in vivo investigation, and displayed a chemical shift sufficiently distinct from that of endogenous fat. 13C-PEG40,000 intravenously injected into mice showed long retention in circulation, leading to its effective accumulation in tumors reflecting the well-known phenomenon that macromolecules accumulate in tumors because of leaky tumor capillaries. These properties of 13C-PEG40,000 allowed visualization of tumors in mice by 13C spectroscopic imaging. These findings suggest that a technique based on 13C-PEG is a promising strategy for tumor detection.

  13. Relationship between the generalized equivalent uniform dose formulation and the Poisson statistics-based tumor control probability model

    International Nuclear Information System (INIS)

    Zhou Sumin; Das, Shiva; Wang Zhiheng; Marks, Lawrence B.

    2004-01-01

    The generalized equivalent uniform dose (GEUD) model uses a power-law formalism, where the outcome is related to the dose via a power law. We herein investigate the mathematical compatibility between this GEUD model and the Poisson statistics based tumor control probability (TCP) model. The GEUD and TCP formulations are combined and subjected to a compatibility constraint equation. This compatibility constraint equates tumor control probability from the original heterogeneous target dose distribution to that from the homogeneous dose from the GEUD formalism. It is shown that this constraint equation possesses a unique, analytical closed-form solution which relates radiation dose to the tumor cell survival fraction. It is further demonstrated that, when there is no positive threshold or finite critical dose in the tumor response to radiation, this relationship is not bounded within the realistic cell survival limits of 0%-100%. Thus, the GEUD and TCP formalisms are, in general, mathematically inconsistent. However, when a threshold dose or finite critical dose exists in the tumor response to radiation, there is a unique mathematical solution for the tumor cell survival fraction that allows the GEUD and TCP formalisms to coexist, provided that all portions of the tumor are confined within certain specific dose ranges

  14. A block matching-based registration algorithm for localization of locally advanced lung tumors

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D., E-mail: gdhugo@vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia, 23298 (United States)

    2014-04-15

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm{sup 3}), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0

  15. A block matching-based registration algorithm for localization of locally advanced lung tumors

    International Nuclear Information System (INIS)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2014-01-01

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm 3 ), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0.001). Left

  16. Neural stem cell sparing by linac based intensity modulated stereotactic radiotherapy in intracranial tumors

    International Nuclear Information System (INIS)

    Oehler, Julia; Brachwitz, Tim; Wendt, Thomas G; Banz, Nico; Walther, Mario; Wiezorek, Tilo

    2013-01-01

    most from IMSRT (p < 0.001). The feasibility of neural stem cell niches sparing with sophisticated linac based inverse IMSRT with 7 beamlets in an unselected cohort of intracranial tumors in relation to topographic situation has been demonstrated. Clinical relevance testing neurotoxicity remains to be demonstrated

  17. Assessing treatment integrity in cognitive-behavioral therapy: comparing session segments with entire sessions.

    Science.gov (United States)

    Weck, Florian; Grikscheit, Florian; Höfling, Volkmar; Stangier, Ulrich

    2014-07-01

    The evaluation of treatment integrity (therapist adherence and competence) is a necessary condition to ensure the internal and external validity of psychotherapy research. However, the evaluation process is associated with high costs, because therapy sessions must be rated by experienced clinicians. It is debatable whether rating session segments is an adequate alternative to rating entire sessions. Four judges evaluated treatment integrity (i.e., therapist adherence and competence) in 84 randomly selected videotapes of cognitive-behavioral therapy for major depressive disorder, social anxiety disorder, and hypochondriasis (from three different treatment outcome studies). In each case, two judges provided ratings based on entire therapy sessions and two on session segments only (i.e., the middle third of the entire sessions). Interrater reliability of adherence and competence evaluations proved satisfactory for ratings based on segments and the level of reliability did not differ from ratings based on entire sessions. Ratings of treatment integrity that were based on entire sessions and session segments were strongly correlated (r=.62 for adherence and r=.73 for competence). The relationship between treatment integrity and outcome was comparable for ratings based on session segments and those based on entire sessions. However, significant relationships between therapist competence and therapy outcome were only found in the treatment of social anxiety disorder. Ratings based on segments proved to be adequate for the evaluation of treatment integrity. The findings demonstrate that session segments are an adequate and cost-effective alternative to entire sessions for the evaluation of therapist adherence and competence. Copyright © 2014. Published by Elsevier Ltd.

  18. Virtual Reality-Based Simulators for Cranial Tumor Surgery: A Systematic Review.

    Science.gov (United States)

    Mazur, Travis; Mansour, Tarek R; Mugge, Luke; Medhkour, Azedine

    2018-02-01

    Virtual reality (VR) simulators have become useful tools in various fields of medicine. Prominent uses of VR technologies include assessment of physician skills and presurgical planning. VR has shown effectiveness in multiple surgical specialties, yet its use in neurosurgery remains limited. To examine all current literature on VR-based simulation for presurgical planning and training in cranial tumor surgeries and to assess the quality of these studies. PubMed and Embase were systematically searched to identify studies that used VR for presurgical planning and/or studies that investigated the use of VR as a training tool from inception to May 25, 2017. The initial search identified 1662 articles. Thirty-seven full-text articles were assessed for inclusion. Nine studies were included. These studies were subdivided into presurgical planning and training using VR. Prospects for VR are bright when surgical planning and skills training are considered. In terms of surgical planning, VR has noted and documented usefulness in the planning of cranial surgeries. Further, VR has been central to establishing reproducible benchmarks of performance in relation to cranial tumor resection, which are helpful not only in showing face and construct validity but also in enhancing neurosurgical training in a way not previously examined. Although additional studies are needed to better delineate the precise role of VR in each of these capacities, these studies stand to show the usefulness of VR in the neurosurgery and highlight the need for further investigation. Published by Elsevier Inc.

  19. Palliative Care Use Among Patients With Solid Cancer Tumors: A National Cancer Data Base Study.

    Science.gov (United States)

    Osagiede, Osayande; Colibaseanu, Dorin T; Spaulding, Aaron C; Frank, Ryan D; Merchea, Amit; Kelley, Scott R; Uitti, Ryan J; Ailawadhi, Sikander

    2018-01-01

    Palliative care has been increasingly recognized as an important part of cancer care but remains underutilized in patients with solid cancers. There is a current gap in knowledge regarding why palliative care is underutilized nationwide. To identify the factors associated with palliative care use among deceased patients with solid cancer tumors. Using the 2016 National Cancer Data Base, we identified deceased patients (2004-2013) with breast, colon, lung, melanoma, and prostate cancer. Data were described as percentages. Associations between palliative care use and patient, facility, and geographic characteristics were evaluated through multivariate logistic regression. A total of 1 840 111 patients were analyzed; 9.6% received palliative care. Palliative care use was higher in the following patient groups: survival >24 months (17% vs 2%), male (54% vs 46%), higher Charlson-Deyo comorbidity score (16% vs 8%), treatment at designated cancer programs (74% vs 71%), lung cancer (76% vs 28%), higher grade cancer (53% vs 24%), and stage IV cancer (59% vs 13%). Patients who lived in communities with a greater percentage of high school degrees had higher odds of receiving palliative care; Central and Pacific regions of the United States had lower odds of palliative care use than the East Coast. Patients with colon, melanoma, or prostate cancer had lower odds of palliative care than patients with breast cancer, whereas those with lung cancer had higher odds. Palliative care use in solid cancer tumors is variable, with a preference for patients with lung cancer, younger age, known insurance status, and higher educational level.

  20. Needle-based polarization-sensitive OCT of breast tumor (Conference Presentation)

    Science.gov (United States)

    Villiger, Martin; Lorenser, Dirk; McLaughlin, Robert A.; Quirk, Bryden C.; Kirk, Rodney W.; Bouma, Brett E.; Sampson, David D.

    2016-03-01

    OCT imaging through miniature needle probes has extended the range of OCT and enabled structural imaging deep inside breast tissue, with the potential to assist in the intraoperative assessment of tumor margins. However, in many situations, scattering contrast alone is insufficient to clearly identify and delineate malignant areas. Here, we present a portable, depth-encoded polarization-sensitive OCT system, connected to a miniature needle probe. From the measured polarization states we constructed the tissue Mueller matrix at each sample location and improved the accuracy of the measured polarization states through incoherent averaging before retrieving the depth-resolved tissue birefringence. With the Mueller matrix at hand, additional polarization properties such as depolarization are readily available. We then imaged freshly excised breast tissue from a patient undergoing lumpectomy. The reconstructed local retardation highlighted regions of connective tissue, which exhibited birefringence due to the abundance of collagen fibers, and offered excellent contrast to areas of malignant tissue, which exhibited less birefringence due to their different tissue composition. Results were validated against co-located histology sections. The combination of needle-based imaging with the complementary contrast provided by polarization-sensitive analysis offers a powerful instrument for advanced tissue imaging and has potential to aid in the assessment of tumor margins during the resection of breast cancer.

  1. Information needs of survivors and families after childhood CNS tumor treatment: a population-based study.

    Science.gov (United States)

    Hovén, Emma; Lannering, Birgitta; Gustafsson, Göran; Boman, Krister K

    2018-05-01

    This study examines information needs and satisfaction with provided information among childhood central nervous system (CNS) tumor survivors and their parents. In a population-based sample of 697 adult survivors in Sweden, 518 survivors and 551 parents provided data. Information needs and satisfaction with information were studied using a multi-dimensional standardized questionnaire addressing information-related issues. Overall, 52% of the survivors and 48% of the parents reported no, or only minor, satisfaction with the extent of provided information, and 51% of the survivors expressed a need for more information than provided. The information received was found useful (to some extent/very much) by 53%, while 47% did not find it useful, or to a minor degree only. Obtaining written material was associated with greater satisfaction and usefulness of information. Dissatisfaction with information was associated with longer time since diagnosis, poorer current health status and female sex. The survivors experienced unmet information needs vis-à-vis late effects, illness education, rehabilitation and psychological services. Overall, parents were more dissatisfied than the survivors. These findings have implications for improvements in information delivery. Information in childhood CNS tumor care and follow-up should specifically address issues where insufficiency was identified, and recognize persistent and with time changing needs at the successive stages of long-term survivorship.

  2. Birth weight and risk of childhood solid tumors in Brazil: a record linkage between population-based data sets

    Directory of Open Access Journals (Sweden)

    Neimar de Paula Silva

    2017-04-01

    Full Text Available ABSTRACT Objective To analyze the relationship between the development of childhood solid tumors and 1 birth weight and 2 fetal growth, using two Brazilian population-based data sets. Methods A case–cohort study was performed using two population-based data sets, and linkage between the Live Birth Information System (Sistema de Informação sobre Nascidos Vivos, SINASC and 14 population-based cancer registries (PBCRs was established. Four controls per case were chosen randomly from the SINASC data set. Tumors were classified as central nervous system (CNS, non-CNS embryonal, and other tumors (“miscellaneous”. Adjustments were made for potential confounders (maternal age, mode of delivery, maternal education, birth order, gestational age, sex, and geographic region. Odds ratios (ORs with 95% confidence intervals (CIs were computed using unconditional logistic regression analysis. Results In a trend analysis, for every 500 g of additional birth weight, the crude OR was 1.12 (CI: 1.00–1.24 and the adjusted OR was 1.02 (CI: 0.90–1.16 for all tumors. For every 1 000 g of additional birth weight, the crude OR was 1.25 (CI: 1.00–1.55 and the adjusted OR was 1.04 (CI: 0.82–1.34 for all tumors. Among children diagnosed after reaching the age of 3 years, in the miscellaneous tumor category, the OR was significantly increased for every additional 500 g and 1 000 g of birth weight. Conclusions The study data suggested that increased birth weight was associated with childhood solid tumor development, especially among children more than 3 years old with “miscellaneous” tumors.

  3. Birth weight and risk of childhood solid tumors in Brazil: a record linkage between population-based data sets.

    Science.gov (United States)

    de Paula Silva, Neimar; de Souza Reis, Rejane; Cunha, Rafael Garcia; Oliveira, Julio Fernando; da Silva de Lima, Fernanda Cristina; Pombo-de-Oliveira, Maria Socorro; Santos, Marceli Oliveira; de Camargo, Beatriz

    2017-04-20

    To analyze the relationship between the development of childhood solid tumors and 1) birth weight and 2) fetal growth, using two Brazilian population-based data sets. A case-cohort study was performed using two population-based data sets, and linkage between the Live Birth Information System (Sistema de Informação sobre Nascidos Vivos, SINASC) and 14 population-based cancer registries (PBCRs) was established. Four controls per case were chosen randomly from the SINASC data set. Tumors were classified as central nervous system (CNS), non-CNS embryonal, and other tumors ("miscellaneous"). Adjustments were made for potential confounders (maternal age, mode of delivery, maternal education, birth order, gestational age, sex, and geographic region). Odds ratios (ORs) with 95% confidence intervals (CIs) were computed using unconditional logistic regression analysis. In a trend analysis, for every 500 g of additional birth weight, the crude OR was 1.12 (CI: 1.00-1.24) and the adjusted OR was 1.02 (CI: 0.90-1.16) for all tumors. For every 1 000 g of additional birth weight, the crude OR was 1.25 (CI: 1.00-1.55) and the adjusted OR was 1.04 (CI: 0.82-1.34) for all tumors. Among children diagnosed after reaching the age of 3 years, in the miscellaneous tumor category, the OR was significantly increased for every additional 500 g and 1 000 g of birth weight. The study data suggested that increased birth weight was associated with childhood solid tumor development, especially among children more than 3 years old with "miscellaneous" tumors.

  4. Pade approximants for entire functions with regularly decreasing Taylor coefficients

    International Nuclear Information System (INIS)

    Rusak, V N; Starovoitov, A P

    2002-01-01

    For a class of entire functions the asymptotic behaviour of the Hadamard determinants D n,m as 0≤m≤m(n)→∞ and n→∞ is described. This enables one to study the behaviour of parabolic sequences from Pade and Chebyshev tables for many individual entire functions. The central result of the paper is as follows: for some sequences {(n,m(n))} in certain classes of entire functions (with regular Taylor coefficients) the Pade approximants {π n,m(n) }, which provide the locally best possible rational approximations, converge to the given function uniformly on the compact set D={z:|z|≤1} with asymptotically best rate

  5. Entirely irrelevant distractors can capture and captivate attention.

    Science.gov (United States)

    Forster, Sophie; Lavie, Nilli

    2011-12-01

    The question of whether a stimulus onset may capture attention when it is entirely irrelevant to the task and even in the absence of any attentional settings for abrupt onset or any dynamic changes has been highly controversial. In the present study, we designed a novel irrelevant capture task to address this question. Participants engaged in a continuous task making sequential forced choice (letter or digit) responses to each item in an alphanumeric matrix that remained on screen throughout many responses. This task therefore involved no attentional settings for onset or indeed any dynamic changes, yet the brief onset of an entirely irrelevant distractor (a cartoon picture) resulted in significant slowing of the two (Experiment 1) or three (Experiment 2) responses immediately following distractor appearance These findings provide a clear demonstration of attention being captured and captivated by a distractor that is entirely irrelevant to any attentional settings of the task.

  6. Selectable six-element multicoil array for entire spine imaging

    International Nuclear Information System (INIS)

    Byrne, J.W.; Bluma-Walter, J.; Prorok, R.J.

    1990-01-01

    This article introduces a new multicoil array that can provide entire spine imaging in two acquisitions with no need to manually reposition either the coil or the patient. A selectable contoured multicoil array with six elements was used to obtain coverage of the entire spine. The first four elements were used for imaging the upper spine region (cervical/thoracic) during the first acquisition, and the last four elements were used for imaging the lower spine region (thoracic/lumbar) during the second acquisition. The overall coil length was approximately 75 cm

  7. Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy.

    Science.gov (United States)

    Son, Keum-Joo; Choi, Ki Ryung; Lee, Seog Jae; Lee, Hyunah

    2016-02-01

    Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT(+) CD11c(+) cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

  8. Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

    Science.gov (United States)

    Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

    2017-11-01

    Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Tumor Hypoxia: Causative Mechanisms, Microregional Heterogeneities, and the Role of Tissue-Based Hypoxia Markers.

    Science.gov (United States)

    Vaupel, Peter; Mayer, Arnulf

    Tumor hypoxia is a hallmark of solid malignant tumor growth, profoundly influences malignant progression and contributes to the development of therapeutic resistance. Pathogenesis of tumor hypoxia is multifactorial, with contributions from both acute and chronic factors. Spatial distribution of hypoxia within tumors is markedly heterogeneous and often changes over time, e.g., during a course of radiotherapy. Substantial changes in the oxygenation status can occur within the distance of a few cell layers, explaining the inability of currently used molecular imaging techniques to adequately assess this crucial trait. Due to the possible importance of tumor hypoxia for clinical decision-making, there is a great demand for molecular tools which may provide the necessary resolution down to the single cell level. Exogenous and endogenous markers of tumor hypoxia have been investigated for this purpose. Their potential use may be greatly enhanced by multiparametric in situ methods in experimental and human tumor tissue.

  10. Imitation-tumor targeting based on continuous-wave near-infrared tomography.

    Science.gov (United States)

    Liu, Dan; Liu, Xin; Zhang, Yan; Wang, Qisong; Lu, Jingyang; Sun, Jinwei

    2017-12-01

    Continuous-wave Near-Infrared (NIR) optical spectroscopy has shown great diagnostic capability in the early tumor detection with advantages of low-cost, portable, non-invasive, and non-radiative. In this paper, Modified Lambert-Beer Theory is deployed to address the low-resolution issues of the NIR technique and to design the tumor detecting and imaging system. Considering that tumor tissues have features such as high blood flow and hypoxia, the proposed technique can detect the location, size, and other information of the tumor tissues by comparing the absorbance between pathological and normal tissues. Finally, the tumor tissues can be imaged through tomographic method. The simulation experiments prove that the proposed technique and designed system can efficiently detect the tumor tissues, achieving imaging precision within 1 mm. The work of the paper has shown great potential in the diagnosis of tumor close to body surface.

  11. Monte Carlo simulation of efficient data acquisition for an entire-body PET scanner

    Energy Technology Data Exchange (ETDEWEB)

    Isnaini, Ismet; Obi, Takashi [Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503 (Japan); Yoshida, Eiji, E-mail: rush@nirs.go.jp [National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Yamaya, Taiga [National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan)

    2014-07-01

    Conventional PET scanners can image the whole body using many bed positions. On the other hand, an entire-body PET scanner with an extended axial FOV, which can trace whole-body uptake images at the same time and improve sensitivity dynamically, has been desired. The entire-body PET scanner would have to process a large amount of data effectively. As a result, the entire-body PET scanner has high dead time at a multiplex detector grouping process. Also, the entire-body PET scanner has many oblique line-of-responses. In this work, we study an efficient data acquisition for the entire-body PET scanner using the Monte Carlo simulation. The simulated entire-body PET scanner based on depth-of-interaction detectors has a 2016-mm axial field-of-view (FOV) and an 80-cm ring diameter. Since the entire-body PET scanner has higher single data loss than a conventional PET scanner at grouping circuits, the NECR of the entire-body PET scanner decreases. But, single data loss is mitigated by separating the axially arranged detector into multiple parts. Our choice of 3 groups of axially-arranged detectors has shown to increase the peak NECR by 41%. An appropriate choice of maximum ring difference (MRD) will also maintain the same high performance of sensitivity and high peak NECR while at the same time reduces the data size. The extremely-oblique line of response for large axial FOV does not contribute much to the performance of the scanner. The total sensitivity with full MRD increased only 15% than that with about half MRD. The peak NECR was saturated at about half MRD. The entire-body PET scanner promises to provide a large axial FOV and to have sufficient performance values without using the full data.

  12. Exosome-Based Cell-Cell Communication in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Joana Maia

    2018-02-01

    Full Text Available Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles, such as exosomes, are emerging as novel cell-cell communication mediators in physiological and pathological scenarios. Exosomes, membrane vesicles of endocytic origin released by all cells (both healthy and diseased, ranging in size from 30 to 150 nm, transport all the main biomolecules, including lipids, proteins, DNAs, messenger RNAs and microRNA, and perform intercellular transfer of components, locally and systemically. By acting not only in tumor cells, but also in tumor-associated cells such as fibroblasts, endothelium, leukocytes and progenitor cells, tumor- and non-tumor cells-derived exosomes have emerged as new players in tumor growth and invasion, tumor-associated angiogenesis, tissue inflammation and immunologic remodeling. In addition, due to their property of carrying molecules from their cell of origin to the peripheral circulation, exosomes have been increasingly studied as sources of tumor biomarkers in liquid biopsies. Here we review the current literature on the participation of exosomes in the communication between tumor and tumor-associated cells, highlighting the role of this process in the setup of tumor microenvironments that modulate tumor initiation and metastasis.

  13. Suprasellar ganglioglioma with unusual diffuse involvement of the entire optico-chiasmal hypothalamic pathway

    Directory of Open Access Journals (Sweden)

    Jalali Rakesh

    2008-01-01

    Full Text Available Gangliogliomas (GG are mixed glioneuronal tumors of the central nervous system (CNS, occurring mostly in the pediatric population, with common sites being temporal lobes and less commonly in the frontal and parietal lobes. We report a case of a 7-year-old child who presented with bilateral visual defects for 6 months. Magnetic resonance imaging (MRI of the brain revealed an intensely enhancing mass lesion with calcification in the sellar and suprasellar region involving the optic chiasm and the left optic nerve. The mass showed almost bilaterally symmetrical diffuse spread along the optic tracts posteriorly and hypothalamus, temporal lobes, thalami and the basal ganglia. The lesion was radiologically indistinguishable from chiasmatic astrocytoma or a germ cell tumor but histopathological features were of a ganglioglioma. While a few optic apparatus gangliogliomas have been reported in the literature, such widespread diffuse involvement of the entire optico-chiasmal hypothalamic pathway is unusual.

  14. A semiautomatic CT-based ensemble segmentation of lung tumors: comparison with oncologists' delineations and with the surgical specimen.

    Science.gov (United States)

    Rios Velazquez, Emmanuel; Aerts, Hugo J W L; Gu, Yuhua; Goldgof, Dmitry B; De Ruysscher, Dirk; Dekker, Andre; Korn, René; Gillies, Robert J; Lambin, Philippe

    2012-11-01

    To assess the clinical relevance of a semiautomatic CT-based ensemble segmentation method, by comparing it to pathology and to CT/PET manual delineations by five independent radiation oncologists in non-small cell lung cancer (NSCLC). For 20 NSCLC patients (stages Ib-IIIb) the primary tumor was delineated manually on CT/PET scans by five independent radiation oncologists and segmented using a CT based semi-automatic tool. Tumor volume and overlap fractions between manual and semiautomatic-segmented volumes were compared. All measurements were correlated with the maximal diameter on macroscopic examination of the surgical specimen. Imaging data are available on www.cancerdata.org. High overlap fractions were observed between the semi-automatically segmented volumes and the intersection (92.5±9.0, mean±SD) and union (94.2±6.8) of the manual delineations. No statistically significant differences in tumor volume were observed between the semiautomatic segmentation (71.4±83.2 cm(3), mean±SD) and manual delineations (81.9±94.1 cm(3); p=0.57). The maximal tumor diameter of the semiautomatic-segmented tumor correlated strongly with the macroscopic diameter of the primary tumor (r=0.96). Semiautomatic segmentation of the primary tumor on CT demonstrated high agreement with CT/PET manual delineations and strongly correlated with the macroscopic diameter considered as the "gold standard". This method may be used routinely in clinical practice and could be employed as a starting point for treatment planning, target definition in multi-center clinical trials or for high throughput data mining research. This method is particularly suitable for peripherally located tumors. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain.

    Science.gov (United States)

    Domingo, Laia; Salas, Dolores; Zubizarreta, Raquel; Baré, Marisa; Sarriugarte, Garbiñe; Barata, Teresa; Ibáñez, Josefa; Blanch, Jordi; Puig-Vives, Montserrat; Fernández, Ana; Castells, Xavier; Sala, Maria

    2014-01-10

    Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd's scale and was conflated into: 75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; cancers, extreme breast density being strongly associated with occult tumors (OR

  16. Optic neuropathy following combined proton and photon radiotherapy for base of skull tumors

    International Nuclear Information System (INIS)

    Kim, June; Munzenrider, John; Maas, Alicea; Finkelstein, Dianne; Liebsch, Norbert; Hug, Eugen; Suit, Herman; Smith, Al; Goitein, Michael

    1997-01-01

    Purpose/Objective: To evaluate the risk of radiation injury to the optic pathway following high dose radiation therapy (RT) for base of skull tumors with regard to the following variables: diabetes, hypertension, number of surgical procedures, use of patch, patch distance, radiation dose, and volume of optic structures receiving 50, 55, or 60 Cobalt Gray Equivalent (CGE). Materials and Methods: A total of 359 patients with base of skull chordoma or low grade chondrosarcoma received high dose radiation therapy. Patients were treated with external beam radiotherapy utilizing protons alone or combined protons and photons. Protons of 160 MeV were delivered at the Harvard Cyclotron Laboratory using a modulated Bragg peak. The tumor dose ranged from 61 to 76 CGE. CGE was used because modulated protons have an RBE of 1.1 compared to 60 Co. Among 359 patients, 85 patients were excluded from evaluation based on age, tumor location, and pre-RT treatment criteria. All 274 evaluable patients had a minimum follow up of 12 months. Medical records were reviewed to determine the actual cause of vision changes. A total of 12 patients with grade II, III, and IV radiation-induced optic neuropathy were identified. Twenty-four patients without complications who closely matched the aforementioned 12 cases with optic neuropathy were selected from the 274 patients as a control group. Dose volume histograms of 12 cases and 24 controls were reviewed to determine minimum, median, and maximum dose to the optic apparatus as well as dose volume at 50, 55, and 60 CGE. Other information regarding remaining potential risk factors, such as diabetes, hypertension, number of surgical procedures, use of patch, and patch distance, was also obtained. Results: A total of 12 patients (4.4%) developed radiation-induced optic neuropathy: 1 grade II, 9 grade III, and 2 grade IV. Specific sites of involvement were left optic nerve in 9, right optic nerve in 5, and chiasm in 4 cases. The duration to the onset

  17. Development and optimization of targeted radionuclide tumor therapy using folate based radiopharmaceuticals

    CERN Document Server

    Reber, Josefine Astrid

    The folate receptor (FR) has been used for a quarter of a century as a tumor-associated target for selective delivery of drugs and imaging agents to cancer cells. While several folic acid radioconjugates have been successfully employed for imaging purposes in (pre)clinical studies, a therapeutic application of folic acid radioconjugates has not yet reached the critical stage which would allow a clinical translation. Due to a substantial expression of the FR in the proximal tubule cells, radiofolates accumulate in the kidneys which are at risk of damage by particle-radiation. To improve this situation, we aimed to develop and evaluate strategies for the performance of FR-targeted radionuclide therapy by decreasing the renal uptake of radiofolates and thereby reducing potential nephrotoxic effects. Two different strategies were investigated. First, the combination of radiofolates with chemotherapeutic agents such as pemetrexed (PMX) and 5-fluorouracil (5-FU) and secondly, an approach based on radioiodinated fol...

  18. PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice.

    Directory of Open Access Journals (Sweden)

    Pie Huda

    Full Text Available 64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was used for the investigations, and it was found that the approximately 13 nm nanodiscs, due to their size, permeate deeply into cancer tissue. This makes them promising candidates for both drug delivery purposes and as advanced imaging agents. For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold.

  19. Entire functions sharing one polynomial with their derivatives

    Indian Academy of Sciences (India)

    restriction of the hyper order less than 1/2, and obtain some uniqueness theorems of a nonconstant entire function and its derivative sharing a finite nonzero complex number. CM. The results in this paper also improve some known results. Some examples are provided to show that the results in this paper are best possible.

  20. Thermodynamics of Quantum Gases for the Entire Range of Temperature

    Science.gov (United States)

    Biswas, Shyamal; Jana, Debnarayan

    2012-01-01

    We have analytically explored the thermodynamics of free Bose and Fermi gases for the entire range of temperature, and have extended the same for harmonically trapped cases. We have obtained approximate chemical potentials for the quantum gases in closed forms of temperature so that the thermodynamic properties of the quantum gases become…

  1. Stereotactic radiosurgery for trigeminal pain secondary to recurrent malignant skull base tumors.

    Science.gov (United States)

    Phan, Jack; Pollard, Courtney; Brown, Paul D; Guha-Thakurta, Nandita; Garden, Adam S; Rosenthal, David I; Fuller, Clifton D; Frank, Steven J; Gunn, G Brandon; Morrison, William H; Ho, Jennifer C; Li, Jing; Ghia, Amol J; Yang, James N; Luo, Dershan; Wang, He C; Su, Shirley Y; Raza, Shaan M; Gidley, Paul W; Hanna, Ehab Y; DeMonte, Franco

    2018-04-27

    OBJECTIVE The objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors. METHODS From 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15-20 Gy) prescribed to the 50% isodose line (range 43%-55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21-27 Gy) prescribed to the 50% isodose line (range 45%-50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS. RESULTS Seven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0-34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p control.

  2. A sequence-based survey of the complex structural organization of tumor genomes

    Energy Technology Data Exchange (ETDEWEB)

    Collins, Colin; Raphael, Benjamin J.; Volik, Stanislav; Yu, Peng; Wu, Chunxiao; Huang, Guiqing; Linardopoulou, Elena V.; Trask, Barbara J.; Waldman, Frederic; Costello, Joseph; Pienta, Kenneth J.; Mills, Gordon B.; Bajsarowicz, Krystyna; Kobayashi, Yasuko; Sridharan, Shivaranjani; Paris, Pamela; Tao, Quanzhou; Aerni, Sarah J.; Brown, Raymond P.; Bashir, Ali; Gray, Joe W.; Cheng, Jan-Fang; de Jong, Pieter; Nefedov, Mikhail; Ried, Thomas; Padilla-Nash, Hesed M.; Collins, Colin C.

    2008-04-03

    The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using End Sequencing Profiling (ESP), which relies on paired-end sequencing of cloned tumor genomes. In this study, brain, breast, ovary and prostate tumors along with three breast cancer cell lines were surveyed with ESP yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization (FISH) confirmed translocations and complex tumor genome structures that include coamplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms (SNPs) revealed candidate somatic mutations and an elevated rate of novel SNPs in an ovarian tumor. These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than previously appreciated and that genomic fusions including fusion transcripts and proteins may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.

  3. Enhancing the effect of radionuclide tumor targeting, using lysosomotropic weak bases

    International Nuclear Information System (INIS)

    Sundberg, Asa Liljegren; Steffen, Ann-Charlott

    2007-01-01

    Purpose: The aim of the present study was to investigate if treatment with lysosomotropic weak bases could increase the intracellular retention of radiohalogens and thereby increase the therapeutic effect of radionuclide tumor targeting. Methods and Materials: Four different lysosomotropic bases, chloroquine, ammonium chloride, amantadine, and thioridazine, were investigated for their ability to increase radiohalogen retention in vitro. The two most promising substances, chloroquine and ammonium chloride, were studied in several cell lines (A431, U343MGaCl2:6, SKOV-3, and SKBR-3) in combination with radiolabeled epidermal growth factor (EGF) or the HER2 binding affibody (Z HER2:4 ) 2 . Results: The uptake and retention of radionuclides was found to be substantially increased by simultaneous treatment with the lysosomotropic bases. The effect was, however, more pronounced in the epidermal growth factor:epidermal growth factor receptor (EGF:EGFR) system than in the (Z HER2:4 ) 2 :HER2 system. The therapeutic effect of ammonium chloride treatment combined with 211 At-EGF was also studied. The effect obtained after combined treatment was found to be much better than after 211 At-EGF treatment alone. Conclusions: The encouraging results from the present study indicate that the use of lysosomotropic weak bases is a promising approach for increasing the therapeutic effect of radionuclide targeting with radiohalogens

  4. Defining Survivorship Trajectories Across Patients With Solid Tumors: An Evidence-Based Approach.

    Science.gov (United States)

    Dood, Robert L; Zhao, Yang; Armbruster, Shannon D; Coleman, Robert L; Tworoger, Shelley; Sood, Anil K; Baggerly, Keith A

    2018-06-02

    Survivorship involves a multidisciplinary approach to surveillance and management of comorbidities and secondary cancers, overseen by oncologists, surgeons, and primary care physicians. Optimal timing and coordination of care, however, is unclear and often based on arbitrary 5-year cutoffs. To determine high- and low-risk periods for all tumor types that could define when survivorship care might best be overseen by oncologists and when to transition to primary care physicians. In this pan-cancer, longitudinal, observational study, excess mortality hazard, calculated as an annualized mortality risk above a baseline population, was plotted over time. The time this hazard took to stabilize defined a high-risk period. The percent morality elevation above age- and sex-matched controls in the latter low-risk period was reported as a mortality gap. The US population-based Surveillance, Epidemiology, and End Results database defined the cancer population, and the US Census life tables defined controls. Incident cases of patients with cancer were separated into tumor types based on International Classification of Diseases for Oncology definitions. Population-level data on incident cancer cases was compared with the general US population. Overall mortality and cause of death were reported on observed cancer cases. A total of 2 317 185 patients (median age, 63 years; 49.8% female) with 66 primary tumor types were evaluated. High-risk surveillance period durations ranged from less than 1 year (breast, prostate, lip, ocular, and parathyroid cancers) up to 19 years (unspecified gastrointestinal cancers). The annualized mortality gap, representing the excess mortality in the stable period, ranged from a median 0.26% to 9.33% excess annual mortality (thyroid and hypopharyngeal cancer populations, respectively). Cluster analysis produced 6 risk cluster groups: group 1, with median survival of 16.2 (5th to 95th percentile range [PR], 10.7-40.2) years and median high-risk period

  5. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  6. Accelerator-based epithermal neutron sources for boron neutron capture therapy of brain tumors.

    Science.gov (United States)

    Blue, Thomas E; Yanch, Jacquelyn C

    2003-01-01

    This paper reviews the development of low-energy light ion accelerator-based neutron sources (ABNSs) for the treatment of brain tumors through an intact scalp and skull using boron neutron capture therapy (BNCT). A major advantage of an ABNS for BNCT over reactor-based neutron sources is the potential for siting within a hospital. Consequently, light-ion accelerators that are injectors to larger machines in high-energy physics facilities are not considered. An ABNS for BNCT is composed of: (1) the accelerator hardware for producing a high current charged particle beam, (2) an appropriate neutron-producing target and target heat removal system (HRS), and (3) a moderator/reflector assembly to render the flux energy spectrum of neutrons produced in the target suitable for patient irradiation. As a consequence of the efforts of researchers throughout the world, progress has been made on the design, manufacture, and testing of these three major components. Although an ABNS facility has not yet been built that has optimally assembled these three components, the feasibility of clinically useful ABNSs has been clearly established. Both electrostatic and radio frequency linear accelerators of reasonable cost (approximately 1.5 M dollars) appear to be capable of producing charged particle beams, with combinations of accelerated particle energy (a few MeV) and beam currents (approximately 10 mA) that are suitable for a hospital-based ABNS for BNCT. The specific accelerator performance requirements depend upon the charged particle reaction by which neutrons are produced in the target and the clinical requirements for neutron field quality and intensity. The accelerator performance requirements are more demanding for beryllium than for lithium as a target. However, beryllium targets are more easily cooled. The accelerator performance requirements are also more demanding for greater neutron field quality and intensity. Target HRSs that are based on submerged-jet impingement and

  7. Solid tumors after chemotherapy or surgery for testicular nonseminoma: a population-based study.

    Science.gov (United States)

    Fung, Chunkit; Fossa, Sophie D; Milano, Michael T; Oldenburg, Jan; Travis, Lois B

    2013-10-20

    Increased risks of solid tumors after older radiotherapy strategies for testicular cancer (TC) are well established. Few population-based studies, however, focus on solid cancer risk among survivors of TC managed with nonradiotherapy approaches. We quantified the site-specific risk of solid cancers among testicular nonseminoma patients treated in the modern era of cisplatin-based chemotherapy, without radiotherapy. Standardized incidence ratios (SIRs) for solid tumors were calculated for 12,691 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2008) and treated initially with either chemotherapy (n = 6,013) or surgery (n = 6,678) without radiotherapy. Patients accrued 116,073 person-years of follow-up. Two hundred ten second solid cancers were observed. No increased risk followed surgery alone (SIR, 0.93; 95% CI, 0.76 to 1.14; n = 99 solid cancers), whereas significantly increased 40% excesses (SIR, 1.43; 95% CI, 1.18 to 1.73; n = 111 solid cancers) occurred after chemotherapy. Increased risks of solid cancers after chemotherapy were observed in most follow-up periods (median latency, 12.5 years), including more than 20 years after treatment (SIR, 1.54; 95% CI, 0.96 to 2.33); significantly increased three- to seven-fold risks occurred for cancers of the kidney (SIR, 3.37; 95% CI, 1.79 to 5.77), thyroid (SIR, 4.40; 95% CI, 2.19 to 7.88), and soft tissue (SIR, 7.49; 95% CI, 3.59 to 13.78). To our knowledge, this is the first large population-based series reporting significantly increased risks of solid cancers among patients with testicular nonseminoma treated in the modern era of cisplatin-based chemotherapy. Subsequent analytic studies should focus on the evaluation of dose-response relationships, types of solid cancers, latency patterns, and interactions with other possible factors, including genetic susceptibility.

  8. Kinematics of the entire East African Rift from GPS velocities

    Science.gov (United States)

    Floyd, M.; King, R. W.

    2017-12-01

    Through a collaborative effort of the GeoPRISMS East Africa Rift GPS Working Group, we have collected and collated all of the publicly available continuous and survey-mode data for the entire rift system between 1994 and 2017 and processed these data as part of a larger velocity solution for Africa, Arabia and western Eurasia. We present here our velocity solution encompassing the major bounding plates and intervening terranes along the East African Rift from the Red Sea to the Malawi Rift and adjacent regions for GPS sites with data spans of at least 2.4 years, and north and east velocity uncertainties less than 1.5 mm/yr. To obtain realistic uncertainties for the velocity estimates, we attempted at each stage of the analysis to account for the character of the noise: During phase processing, we used an elevation-dependent weighting based on the phase residuals for each station; we then examined each position time series, removing outliers and reweighting appropriately to account for the white noise component of the errors; and e accounted for temporal correlations by estimating an equivalent random-walk magnitude for each continuous site and applying the median value (0.5 mm/√yr) to all survey-mode sites. We rigorously estimate relative rotation rates of Nubia, by choosing subset of well-determined sites such that the effective weights of western, northeastern and southern Africa were roughly equivalent, and Somalia, for which the estimate is dominated by three sites (MALI, RCMN, SEY1) whose uncertainties are a factor of 2-3 smaller than those of the other sites. For both plates, the weighted root-mean-square of the velocity residuals is 0.5 mm/yr. Our unified velocity solution provides a geodetic framework and constraints on the continental-scale kinematics of surface motions as well as more local effects both within and outside of the rift structures. Specific focus areas with denser coverage than previous fields include the Danakil block, the Afar Rift, the

  9. Evaluation of amplitude-based sorting algorithm to reduce lung tumor blurring in PET images using 4D NCAT phantom.

    Science.gov (United States)

    Wang, Jiali; Byrne, James; Franquiz, Juan; McGoron, Anthony

    2007-08-01

    develop and validate a PET sorting algorithm based on the respiratory amplitude to correct for abnormal respiratory cycles. using the 4D NCAT phantom model, 3D PET images were simulated in lung and other structures at different times within a respiratory cycle and noise was added. To validate the amplitude binning algorithm, NCAT phantom was used to simulate one case of five different respiratory periods and another case of five respiratory periods alone with five respiratory amplitudes. Comparison was performed for gated and un-gated images and for the new amplitude binning algorithm with the time binning algorithm by calculating the mean number of counts in the ROI (region of interest). an average of 8.87+/-5.10% improvement was reported for total 16 tumors with different tumor sizes and different T/B (tumor to background) ratios using the new sorting algorithm. As both the T/B ratio and tumor size decreases, image degradation due to respiration increases. The greater benefit for smaller diameter tumor and lower T/B ratio indicates a potential improvement in detecting more problematic tumors.

  10. Paper-Based MicroRNA Expression Profiling from Plasma and Circulating Tumor Cells.

    Science.gov (United States)

    Leong, Sai Mun; Tan, Karen Mei-Ling; Chua, Hui Wen; Huang, Mo-Chao; Cheong, Wai Chye; Li, Mo-Huang; Tucker, Steven; Koay, Evelyn Siew-Chuan

    2017-03-01

    Molecular characterization of circulating tumor cells (CTCs) holds great promise for monitoring metastatic progression and characterizing metastatic disease. However, leukocyte and red blood cell contamination of routinely isolated CTCs makes CTC-specific molecular characterization extremely challenging. Here we report the use of a paper-based medium for efficient extraction of microRNAs (miRNAs) from limited amounts of biological samples such as rare CTCs harvested from cancer patient blood. Specifically, we devised a workflow involving the use of Flinders Technology Associates (FTA) ® Elute Card with a digital PCR-inspired "partitioning" method to extract and purify miRNAs from plasma and CTCs. We demonstrated the sensitivity of this method to detect miRNA expression from as few as 3 cancer cells spiked into human blood. Using this method, background miRNA expression was excluded from contaminating blood cells, and CTC-specific miRNA expression profiles were derived from breast and colorectal cancer patients. Plasma separated out during purification of CTCs could likewise be processed using the same paper-based method for miRNA detection, thereby maximizing the amount of patient-specific information that can be derived from a single blood draw. Overall, this paper-based extraction method enables an efficient, cost-effective workflow for maximized recovery of small RNAs from limited biological samples for downstream molecular analyses. © 2016 American Association for Clinical Chemistry.

  11. PCA based clustering for brain tumor segmentation of T1w MRI images.

    Science.gov (United States)

    Kaya, Irem Ersöz; Pehlivanlı, Ayça Çakmak; Sekizkardeş, Emine Gezmez; Ibrikci, Turgay

    2017-03-01

    Medical images are huge collections of information that are difficult to store and process consuming extensive computing time. Therefore, the reduction techniques are commonly used as a data pre-processing step to make the image data less complex so that a high-dimensional data can be identified by an appropriate low-dimensional representation. PCA is one of the most popular multivariate methods for data reduction. This paper is focused on T1-weighted MRI images clustering for brain tumor segmentation with dimension reduction by different common Principle Component Analysis (PCA) algorithms. Our primary aim is to present a comparison between different variations of PCA algorithms on MRIs for two cluster methods. Five most common PCA algorithms; namely the conventional PCA, Probabilistic Principal Component Analysis (PPCA), Expectation Maximization Based Principal Component Analysis (EM-PCA), Generalize Hebbian Algorithm (GHA), and Adaptive Principal Component Extraction (APEX) were applied to reduce dimensionality in advance of two clustering algorithms, K-Means and Fuzzy C-Means. In the study, the T1-weighted MRI images of the human brain with brain tumor were used for clustering. In addition to the original size of 512 lines and 512 pixels per line, three more different sizes, 256 × 256, 128 × 128 and 64 × 64, were included in the study to examine their effect on the methods. The obtained results were compared in terms of both the reconstruction errors and the Euclidean distance errors among the clustered images containing the same number of principle components. According to the findings, the PPCA obtained the best results among all others. Furthermore, the EM-PCA and the PPCA assisted K-Means algorithm to accomplish the best clustering performance in the majority as well as achieving significant results with both clustering algorithms for all size of T1w MRI images. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Clinical performance of LOCI™-based tumor marker assays for tumor markers CA 15-3, CA 125, CEA, CA 19-9 and AFP in gynecological cancers.

    Science.gov (United States)

    Dolscheid-Pommerich, Ramona C; Keyver-Paik, Mignon; Hecking, Thomas; Kuhn, Walther; Hartmann, Gunther; Stoffel-Wagner, Birgit; Holdenrieder, Stefan

    2017-10-01

    Evidence is sparse regarding the clinical performance of luminescent oxygen channeling immunoassays-based tumor marker assays in gynecological cancer. Analyzing serum samples of 336 patients with Dimension™Vista1500, we investigated the diagnostic power of carbohydrate antigen 15-3, carbohydrate antigen 125, carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein in patients suffering from different types of gynecological cancer and precancerous gynecological diseases and compared findings to appropriate control groups. The cohort comprised 177 female patients with gynecological cancers (73 breast, 22 cervical, 16 endometrial, 17 vulva, and 49 ovarian cancers), 26 patients with precancerous gynecological diseases (11 vulva, 4 cervical, and 10 breast), 109 patients with benign gynecological diseases, and 24 healthy controls. Discriminative power was assessed by areas under the curve in receiver operating characteristic curves, and sensitivities were determined at a fixed specificity of 95%. Levels of biomarkers in healthy controls were in the expected ranges and a discriminative power between gynecological cancers and healthy controls was observed for several tumor markers. Established tumor type-associated markers were elevated in specific gynecological cancers and benign controls as well as within precancerous gynecological diseases and healthy control group. In ovarian cancer, carbohydrate antigen 125 and carbohydrate antigen 15-3 were significantly elevated compared to the respective benign diseases. Carbohydrate antigen 125 was the most conclusive marker (area under the curve = 0.86% and 77.6% sensitivity at 95% specificity). In breast cancer, carcinoembryonic antigen and carbohydrate antigen 15-3 were significantly higher than in the respective benign diseases. Carcinoembryonic antigen achieved the most conclusive area under the curve (0.65) with 31.5% sensitivity at 95% specificity. None of the investigated markers was found to be of

  13. Entirely irrelevant distractors can capture and captivate attention

    OpenAIRE

    Forster, Sophie; Lavie, Nilli

    2011-01-01

    The question of whether a stimulus onset may capture attention when it is entirely irrelevant to the task and even in the absence of any attentional settings for abrupt onset or any dynamic changes has been highly controversial. In the present study, we designed a novel irrelevant capture task to address this question. Participants engaged in a continuous task making sequential forced choice (letter or digit) responses to each item in an alphanumeric matrix that remained on screen throughout ...

  14. Completely monotonic functions related to logarithmic derivatives of entire functions

    DEFF Research Database (Denmark)

    Pedersen, Henrik Laurberg

    2011-01-01

    The logarithmic derivative l(x) of an entire function of genus p and having only non-positive zeros is represented in terms of a Stieltjes function. As a consequence, (-1)p(xml(x))(m+p) is a completely monotonic function for all m ≥ 0. This generalizes earlier results on complete monotonicity...... of functions related to Euler's psi-function. Applications to Barnes' multiple gamma functions are given....

  15. Detection of T790M, the acquired resistance EGFR mutation, by tumor biopsy versus noninvasive blood-based analyses

    Science.gov (United States)

    Sundaresan, Tilak K.; Sequist, Lecia V.; Heymach, John V.; Riely, Gregory J.; Jänne, Pasi A.; Koch, Walter H.; Sullivan, James P.; Fox, Douglas B.; Maher, Robert; Muzikansky, Alona; Webb, Andrew; Tran, Hai T.; Giri, Uma; Fleisher, Martin; Yu, Helena A.; Wei, Wen; Johnson, Bruce E.; Barber, Thomas A.; Walsh, John R.; Engelman, Jeffrey A.; Stott, Shannon L.; Kapur, Ravi; Maheswaran, Shyamala; Toner, Mehmet

    2015-01-01

    Purpose The T790M gatekeeper mutation in the Epidermal Growth Factor Receptor (EGFR) is acquired by some EGFR-mutant non-small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKIs). As third generation EGFR TKIs that overcome T790M-associated resistance become available, noninvasive approaches to T790M detection will become critical to guide management. Experimental Design As part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis of 40 patients with EGFR-mutant tumors progressing on EGFR TKI therapy. We compared the T790M genotype from tumor biopsies with analysis of simultaneously collected circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). Results T790M genotypes were successfully obtained in 30 (75%) tumor biopsies, 28 (70%) CTC samples and 32 (80%) ctDNA samples. The resistance-associated mutation was detected in 47–50% of patients using each of the genotyping assays, with concordance among them ranging from 57–74%. While CTC- and ctDNA-based genotyping were each unsuccessful in 20–30% of cases, the two assays together enabled genotyping in all patients with an available blood sample, and they identified the T790M mutation in 14 (35%) patients in whom the concurrent biopsy was negative or indeterminate. Conclusion Discordant genotypes between tumor biopsy and blood-based analyses may result from technological differences, as well as sampling different tumor cell populations. The use of complementary approaches may provide the most complete assessment of each patient’s cancer, which should be validated in predicting response to T790M-targeted inhibitors. PMID:26446944

  16. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    International Nuclear Information System (INIS)

    Park, Ji-Ae; Lee, Yong Jin; Ko, In Ok; Kim, Tae-Jeong; Chang, Yongmin; Lim, Sang Moo; Kim, Kyeong Min; Kim, Jung Young

    2014-01-01

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images

  17. Development of amphiphilic gamma-PGA-nanoparticle based tumor vaccine: potential of the nanoparticulate cytosolic protein delivery carrier.

    Science.gov (United States)

    Yoshikawa, Tomoaki; Okada, Naoki; Oda, Atsushi; Matsuo, Kazuhiko; Matsuo, Keisuke; Mukai, Yohei; Yoshioka, Yasuo; Akagi, Takami; Akashi, Mitsuru; Nakagawa, Shinsaku

    2008-02-08

    Nanoscopic therapeutic systems that incorporate biomacromolecules, such as protein and peptides, are emerging as the next generation of nanomedicine aimed at improving the therapeutic efficacy of biomacromolecular drugs. In this study, we report that poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent protein delivery carriers for tumor vaccines that delivered antigenic proteins to antigen-presenting cells and elicited potent immune responses. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins through cytosolic translocation from the endosomes, which is a key process of gamma-PGA NP-mediated anti-tumor immune responses. Our findings suggest that the gamma-PGA NP system is suitable for the intracellular delivery of protein-based drugs as well as tumor vaccines.

  18. The prognostic value of dividing epithelial ovarian cancer into type I and type II tumors based on pathologic characteristics

    DEFF Research Database (Denmark)

    Prahm, Kira Philipsen; Karlsen, Mona Aarenstrup; Høgdall, Estrid

    2015-01-01

    OBJECTIVE: To investigate the prognostic significance of dividing epithelial ovarian cancer (EOC) in type I and type II tumors based on pathologic variables. METHODS: We used the Danish Gynecologic Cancer Database to identify all patients diagnosed with EOC from 2005 to 2012. Information on histo......OBJECTIVE: To investigate the prognostic significance of dividing epithelial ovarian cancer (EOC) in type I and type II tumors based on pathologic variables. METHODS: We used the Danish Gynecologic Cancer Database to identify all patients diagnosed with EOC from 2005 to 2012. Information...... for survival confirmed the increased overall survival for type I tumors after two years of follow-up (hazard ratio: 1.85, 95% confidence interval: 1.35-2.54, Pbased on pathologic variables was associated with an increased risk of death...

  19. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji-Ae, E-mail: jpark@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yong Jin; Ko, In Ok [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Tae-Jeong; Chang, Yongmin [Institute of Biomedical Engineering, Kyungpook National University, Daegu (Korea, Republic of); Lim, Sang Moo [Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kyeong Min [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jung Young, E-mail: jykim@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-12-12

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

  20. Nanometer-scale anatomy of entire Stardust tracks

    Science.gov (United States)

    Nakamura-Messenger, Keiko; Keller, Lindsay P.; Clemett, Simon J.; Messenger, Scott; Ito, Motoo

    2011-07-01

    We have developed new sample preparation and analytical techniques tailored for entire aerogel tracks of Wild 2 sample analyses both on "carrot" and "bulbous" tracks. We have successfully ultramicrotomed an entire track along its axis while preserving its original shape. This innovation allowed us to examine the distribution of fragments along the entire track from the entrance hole all the way to the terminal particle. The crystalline silicates we measured have Mg-rich compositions and O isotopic compositions in the range of meteoritic materials, implying that they originated in the inner solar system. The terminal particle of the carrot track is a 16O-rich forsteritic grain that may have formed in a similar environment as Ca-, Al-rich inclusions and amoeboid olivine aggregates in primitive carbonaceous chondrites. The track also contains submicron-sized diamond grains likely formed in the solar system. Complex aromatic hydrocarbons distributed along aerogel tracks and in terminal particles. These organics are likely cometary but affected by shock heating.

  1. SNPase-ARMS qPCR: Ultrasensitive Mutation-Based Detection of Cell-Free Tumor DNA in Melanoma Patients.

    Directory of Open Access Journals (Sweden)

    Julia Stadler

    Full Text Available Cell-free circulating tumor DNA in the plasma of cancer patients has become a common point of interest as indicator of therapy options and treatment response in clinical cancer research. Especially patient- and tumor-specific single nucleotide variants that accurately distinguish tumor DNA from wild type DNA are promising targets. The reliable detection and quantification of these single-base DNA variants is technically challenging. Currently, a variety of techniques is applied, with no apparent "gold standard". Here we present a novel qPCR protocol that meets the conditions of extreme sensitivity and specificity that are required for detection and quantification of tumor DNA. By consecutive application of two polymerases, one of them designed for extreme base-specificity, the method reaches unprecedented sensitivity and specificity. Three qPCR assays were tested with spike-in experiments, specific for point mutations BRAF V600E, PTEN T167A and NRAS Q61L of melanoma cell lines. It was possible to detect down to one copy of tumor DNA per reaction (Poisson distribution, at a background of up to 200 000 wild type DNAs. To prove its clinical applicability, the method was successfully tested on a small cohort of BRAF V600E positive melanoma patients.

  2. Optimal technique of linear accelerator–based stereotactic radiosurgery for tumors adjacent to brainstem

    International Nuclear Information System (INIS)

    Chang, Chiou-Shiung; Hwang, Jing-Min; Tai, Po-An; Chang, You-Kang; Wang, Yu-Nong; Shih, Rompin; Chuang, Keh-Shih

    2016-01-01

    Stereotactic radiosurgery (SRS) is a well-established technique that is replacing whole-brain irradiation in the treatment of intracranial lesions, which leads to better preservation of brain functions, and therefore a better quality of life for the patient. There are several available forms of linear accelerator (LINAC)–based SRS, and the goal of the present study is to identify which of these techniques is best (as evaluated by dosimetric outcomes statistically) when the target is located adjacent to brainstem. We collected the records of 17 patients with lesions close to the brainstem who had previously been treated with single-fraction radiosurgery. In all, 5 different lesion catalogs were collected, and the patients were divided into 2 distance groups—1 consisting of 7 patients with a target-to-brainstem distance of less than 0.5 cm, and the other of 10 patients with a target-to-brainstem distance of ≥ 0.5 and < 1 cm. Comparison was then made among the following 3 types of LINAC-based radiosurgery: dynamic conformal arcs (DCA), intensity-modulated radiosurgery (IMRS), and volumetric modulated arc radiotherapy (VMAT). All techniques included multiple noncoplanar beams or arcs with or without intensity-modulated delivery. The volume of gross tumor volume (GTV) ranged from 0.2 cm 3 to 21.9 cm 3 . Regarding the dose homogeneity index (HI ICRU ) and conformity index (CI ICRU ) were without significant difference between techniques statistically. However, the average CI ICRU = 1.09 ± 0.56 achieved by VMAT was the best of the 3 techniques. Moreover, notable improvement in gradient index (GI) was observed when VMAT was used (0.74 ± 0.13), and this result was significantly better than those achieved by the 2 other techniques (p < 0.05). For V 4 Gy of brainstem, both VMAT (2.5%) and IMRS (2.7%) were significantly lower than DCA (4.9%), both at the p < 0.05 level. Regarding V 2 Gy of normal brain, VMAT plans had attained 6.4 ± 5%; this was significantly better

  3. Tumor tracking and motion compensation with an adaptive tumor tracking system (ATTS): System description and prototype testing

    International Nuclear Information System (INIS)

    Wilbert, Juergen; Meyer, Juergen; Baier, Kurt; Guckenberger, Matthias; Herrmann, Christian; Hess, Robin; Janka, Christian; Ma Lei; Mersebach, Torben; Richter, Anne; Roth, Michael; Schilling, Klaus; Flentje, Michael

    2008-01-01

    A novel system for real-time tumor tracking and motion compensation with a robotic HexaPOD treatment couch is described. The approach is based on continuous tracking of the tumor motion in portal images without implanted fiducial markers, using the therapeutic megavoltage beam, and tracking of abdominal breathing motion with optical markers. Based on the two independently acquired data sets the table movements for motion compensation are calculated. The principle of operation of the entire prototype system is detailed first. In the second part the performance of the HexaPOD couch was investigated with a robotic four-dimensional-phantom capable of simulating real patient tumor trajectories in three-dimensional space. The performance and limitations of the HexaPOD table and the control system were characterized in terms of its dynamic behavior. The maximum speed and acceleration of the HexaPOD were 8 mm/s and 34.5 mm/s 2 in the lateral direction, and 9.5 mm/s and 29.5 mm/s 2 in longitudinal and anterior-posterior direction, respectively. Base line drifts of the mean tumor position of realistic lung tumor trajectories could be fully compensated. For continuous tumor tracking and motion compensation a reduction of tumor motion up to 68% of the original amplitude was achieved. In conclusion, this study demonstrated that it is technically feasible to compensate breathing induced tumor motion in the lung with the adaptive tumor tracking system

  4. Fluorodeoxyglucose-based positron emission tomography imaging to monitor drug responses in hematological tumors

    NARCIS (Netherlands)

    Newbold, Andrea; Martin, Ben P.; Cullinane, Carleen; Bots, Michael

    2014-01-01

    Positron emission tomography (PET) can be used to monitor the uptake of the labeled glucose analog fluorodeoxyglucose (¹⁸F-FDG), a process that is generally believed to reflect viable tumor cell mass. The use of ¹⁸F-FDG PET can be helpful in documenting over time the reduction in tumor mass volume

  5. A neuropathology-based approach to epilepsy surgery in brain tumors and proposal for a new terminology use for long-term epilepsy-associated brain tumors

    NARCIS (Netherlands)

    Blumcke, Ingmar; Aronica, Eleonora; Urbach, Horst; Alexopoulos, Andreas; Gonzalez-Martinez, Jorge A.

    2014-01-01

    Every fourth patient submitted to epilepsy surgery suffers from a brain tumor. Microscopically, these neoplasms present with a wide-ranging spectrum of glial or glio-neuronal tumor subtypes. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNTs) are the most frequently recognized

  6. Optimal technique of linear accelerator-based stereotactic radiosurgery for tumors adjacent to brainstem.

    Science.gov (United States)

    Chang, Chiou-Shiung; Hwang, Jing-Min; Tai, Po-An; Chang, You-Kang; Wang, Yu-Nong; Shih, Rompin; Chuang, Keh-Shih

    2016-01-01

    Stereotactic radiosurgery (SRS) is a well-established technique that is replacing whole-brain irradiation in the treatment of intracranial lesions, which leads to better preservation of brain functions, and therefore a better quality of life for the patient. There are several available forms of linear accelerator (LINAC)-based SRS, and the goal of the present study is to identify which of these techniques is best (as evaluated by dosimetric outcomes statistically) when the target is located adjacent to brainstem. We collected the records of 17 patients with lesions close to the brainstem who had previously been treated with single-fraction radiosurgery. In all, 5 different lesion catalogs were collected, and the patients were divided into 2 distance groups-1 consisting of 7 patients with a target-to-brainstem distance of less than 0.5cm, and the other of 10 patients with a target-to-brainstem distance of ≥ 0.5 and linear accelerator is only 1 modality can to establish for SRS treatment. Based on statistical evidence retrospectively, we recommend VMAT as the optimal technique for delivering treatment to tumors adjacent to brainstem. Copyright © 2016 American Association of Medical Dosimetrists. All rights reserved.

  7. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Meyer, Morten; Petterson, Stine Asferg

    2016-01-01

    AIMS: Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking...... invasion and tumor stemness into account. METHODS: Glioblastoma stem cell-like containing spheroid (GSS) cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains...... of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models. RESULTS: We observed a pronounced invasion into brain slice...

  8. Tumor and Stromal-Based Contributions to Head and Neck Squamous Cell Carcinoma Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Markwell, Steven M.; Weed, Scott A., E-mail: scweed@hsc.wvu.edu [Department of Neurobiology and Anatomy, Program in Cancer Cell Biology, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506 (United States)

    2015-02-27

    Head and neck squamous cell carcinoma (HNSCC) is typically diagnosed at advanced stages with evident loco-regional and/or distal metastases. The prevalence of metastatic lesions directly correlates with poor patient outcome, resulting in high patient mortality rates following metastatic development. The progression to metastatic disease requires changes not only in the carcinoma cells, but also in the surrounding stromal cells and tumor microenvironment. Within the microenvironment, acellular contributions from the surrounding extracellular matrix, along with contributions from various infiltrating immune cells, tumor associated fibroblasts, and endothelial cells facilitate the spread of tumor cells from the primary site to the rest of the body. Thus far, most attempts to limit metastatic spread through therapeutic intervention have failed to show patient benefit in clinic trails. The goal of this review is highlight the complexity of invasion-promoting interactions in the HNSCC tumor microenvironment, focusing on contributions from tumor and stromal cells in order to assist future therapeutic development and patient treatment.

  9. Valine-based biphenylsulphonamide matrix metalloproteinase inhibitors as tumor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Oltenfreiter, Ruth [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium)]. E-mail: ruth.oltenfreiter@ugent.be; Staelens, Ludovicus [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium); Kersemans, Veerle [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium); Cornelissen, Bart [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium); Frankenne, Francis [Laboratory of Tumor and Developmental Biology, University of Liege, Sart-Tilman, Liege (Belgium); Foidart, Jean-Michel [Laboratory of Tumor and Developmental Biology, University of Liege, Sart-Tilman, Liege (Belgium); Wiele, Christophe van de [Division of Nuclear Medicine, Gent University Hospital, De Pintelaan 185, 9000 Gent (Belgium); Slegers, Guido [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium)

    2006-06-15

    Among matrix metalloproteinases (MMPs), the subfamily of gelatinases (MMP-2, MMP-9) is of particular interest due to their ability to degrade type IV collagen and other non-fibrillar collagen domains and proteins such as fibronectin and laminin. Whilst malignant cells often over-express various MMPs, the gelatinases have been most consistently detected in malignant tissues and associated with tumor growth, metastatic potential and angiogenesis. Radiosynthesis of carboxylic (1') and hydroxamic (2') MMPIs resulted in radiochemical yields of 70+/-5% (n=6) and 60+/-5% (n=4), respectively. Evaluation in A549-inoculated athymic mice showed a tumor uptake of 2.0+/-0.7%ID/g (3h p.i.), a tumor/blood ratio of 0.5 and a tumor/muscle ratio of 4.6 at 48hp.i. for 1'. For compound 2' a tumor uptake of 0.7+/-0.2%ID/g (3hp.i.), a tumor/blood ratio of 1.2 and a tumor/muscle ratio of 1.8 at 24hp.i. were observed. HPLC analysis of the blood (plasma) showed no dehalogenation or other metabolites of 1' 2hp.i. For compound 2', 65.4% of intact compound was found in the blood (plasma) and one polar metabolite (31%) was detected whereas in the tumor 91.8% of the accumulated activity was caused by intact compound and only 8.1% by the metabolite. Planar imaging, using a Toshiba GCA-9300A/hg SPECT camera, showed that tumor tissue could be visualized and that image quality improved by decreasing specific activity resulting in lower liver uptake, indicating some degree of saturable binding in the liver. In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that MMP inhibitors could have potential as tumor imaging agents, but that further research is necessary.

  10. Valine-based biphenylsulphonamide matrix metalloproteinase inhibitors as tumor imaging agents

    International Nuclear Information System (INIS)

    Oltenfreiter, Ruth; Staelens, Ludovicus; Kersemans, Veerle; Cornelissen, Bart; Frankenne, Francis; Foidart, Jean-Michel; Wiele, Christophe van de; Slegers, Guido

    2006-01-01

    Among matrix metalloproteinases (MMPs), the subfamily of gelatinases (MMP-2, MMP-9) is of particular interest due to their ability to degrade type IV collagen and other non-fibrillar collagen domains and proteins such as fibronectin and laminin. Whilst malignant cells often over-express various MMPs, the gelatinases have been most consistently detected in malignant tissues and associated with tumor growth, metastatic potential and angiogenesis. Radiosynthesis of carboxylic (1') and hydroxamic (2') MMPIs resulted in radiochemical yields of 70+/-5% (n=6) and 60+/-5% (n=4), respectively. Evaluation in A549-inoculated athymic mice showed a tumor uptake of 2.0+/-0.7%ID/g (3h p.i.), a tumor/blood ratio of 0.5 and a tumor/muscle ratio of 4.6 at 48hp.i. for 1'. For compound 2' a tumor uptake of 0.7+/-0.2%ID/g (3hp.i.), a tumor/blood ratio of 1.2 and a tumor/muscle ratio of 1.8 at 24hp.i. were observed. HPLC analysis of the blood (plasma) showed no dehalogenation or other metabolites of 1' 2hp.i. For compound 2', 65.4% of intact compound was found in the blood (plasma) and one polar metabolite (31%) was detected whereas in the tumor 91.8% of the accumulated activity was caused by intact compound and only 8.1% by the metabolite. Planar imaging, using a Toshiba GCA-9300A/hg SPECT camera, showed that tumor tissue could be visualized and that image quality improved by decreasing specific activity resulting in lower liver uptake, indicating some degree of saturable binding in the liver. In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that MMP inhibitors could have potential as tumor imaging agents, but that further research is necessary

  11. Comparison of continuous versus categorical tumor measurement-based metrics to predict overall survival in cancer treatment trials

    Science.gov (United States)

    An, Ming-Wen; Mandrekar, Sumithra J.; Branda, Megan E.; Hillman, Shauna L.; Adjei, Alex A.; Pitot, Henry; Goldberg, Richard M.; Sargent, Daniel J.

    2011-01-01

    Purpose The categorical definition of response assessed via the Response Evaluation Criteria in Solid Tumors has documented limitations. We sought to identify alternative metrics for tumor response that improve prediction of overall survival. Experimental Design Individual patient data from three North Central Cancer Treatment Group trials (N0026, n=117; N9741, n=1109; N9841, n=332) were used. Continuous metrics of tumor size based on longitudinal tumor measurements were considered in addition to a trichotomized response (TriTR: Response vs. Stable vs. Progression). Cox proportional hazards models, adjusted for treatment arm and baseline tumor burden, were used to assess the impact of the metrics on subsequent overall survival, using a landmark analysis approach at 12-, 16- and 24-weeks post baseline. Model discrimination was evaluated using the concordance (c) index. Results The overall best response rates for the three trials were 26%, 45%, and 25% respectively. While nearly all metrics were statistically significantly associated with overall survival at the different landmark time points, the c-indices for the traditional response metrics ranged from 0.59-0.65; for the continuous metrics from 0.60-0.66 and for the TriTR metrics from 0.64-0.69. The c-indices for TriTR at 12-weeks were comparable to those at 16- and 24-weeks. Conclusions Continuous tumor-measurement-based metrics provided no predictive improvement over traditional response based metrics or TriTR; TriTR had better predictive ability than best TriTR or confirmed response. If confirmed, TriTR represents a promising endpoint for future Phase II trials. PMID:21880789

  12. Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered MicroRNA expression in solid tumors

    DEFF Research Database (Denmark)

    Sempere, Lorenzo F; Preis, Meir; Yezefski, Todd

    2010-01-01

    of altered miRNA expression in solid tumors, we developed a sensitive fluorescence-based in situ hybridization (ISH) method to visualize miRNA accumulation within individual cells in formalin-fixed, paraffin-embedded tissue specimens. This ISH method was implemented to be compatible with routine clinical...

  13. In-silico oncology: an approximate model of brain tumor mass effect based on directly manipulated free form deformation

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Stefan; Mang, Andreas; Toma, Alina; Buzug, Thorsten M. [University of Luebeck (Germany). Institute of Medical Engineering

    2010-12-15

    The present work introduces a novel method for approximating mass effect of primary brain tumors. The spatio-temporal dynamics of cancerous cells are modeled by means of a deterministic reaction-diffusion equation. Diffusion tensor information obtained from a probabilistic diffusion tensor imaging atlas is incorporated into the model to simulate anisotropic diffusion of cancerous cells. To account for the expansive nature of the tumor, the computed net cell density of malignant cells is linked to a parametric deformation model. This mass effect model is based on the so-called directly manipulated free form deformation. Spatial correspondence between two successive simulation steps is established by tracking landmarks, which are attached to the boundary of the gross tumor volume. The movement of these landmarks is used to compute the new configuration of the control points and, hence, determines the resulting deformation. To prevent a deformation of rigid structures (i.e. the skull), fixed shielding landmarks are introduced. In a refinement step, an adaptive landmark scheme ensures a dense sampling of the tumor isosurface, which in turn allows for an appropriate representation of the tumor shape. The influence of different parameters on the model is demonstrated by a set of simulations. Additionally, simulation results are qualitatively compared to an exemplary set of clinical magnetic resonance images of patients diagnosed with high-grade glioma. Careful visual inspection of the results demonstrates the potential of the implemented model and provides first evidence that the computed approximation of tumor mass effect is sensible. The shape of diffusive brain tumors (glioblastoma multiforme) can be recovered and approximately matches the observations in real clinical data. (orig.)

  14. Targeting Multiple Tumors Using T-Cells Engineered to Express a Natural Cytotoxicity Receptor 2-Based Chimeric Receptor

    Directory of Open Access Journals (Sweden)

    Vasyl Eisenberg

    2017-09-01

    Full Text Available Recent developments in cancer treatment are demonstrating the increasing and powerful potential of immunotherapeutic strategies. In this regard, the adoptive transfer of tumor-specific T-lymphocytes approaches can lead to tumor regression in cancer patients. More recently, the use of T-cells genetically engineered to express cancer-specific receptors such as the anti-CD19 chimeric antigen receptor (CAR continues to show promise for the treatment of hematological malignancies. Still, there is a crucial need to develop efficient CAR-T cell approaches for the treatment of solid tumors. It has been shown that other lymphocytes such as natural killer (NK cells can demonstrate potent antitumor function—nonetheless, their use in immunotherapy is rather limited due to difficulties in expanding these cells to therapeutically relevant numbers and to suppression by endogenous inhibitory mechanisms. Cancer recognition by NK cells is partly mediated by molecules termed natural cytotoxicity receptors (NCRs. In the present study, we hypothesize that it is possible to endow T-cells with an NK recognition pattern, providing them with a mean to recognize tumor cells, in a non-MHC restricted way. To test this, we genetically modified human T-cells with different chimeric receptors based on the human NCR2 molecule and then assessed their antitumor activity in vitro and in vivo. Our results show that expression in primary lymphocytes of an NCR2-derived CAR, termed s4428z, confers T-cells with the ability to specifically recognize heterogeneous tumors and to mediate tumor cytotoxicity in a mouse model. This study demonstrates the benefit of combining tumor recognition capability of NK cells with T cell effectiveness to improve cancer immunotherapy.

  15. Pitfalls in the assessment of radioresponse as determined by tumor regression. Consideration based on the location and histologic constitution of tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ohara, Kiyoshi; Shimizu, Wakako; Itai, Yuji [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

    2000-05-01

    To prove the following hypotheses regarding tumor shrinkage after radiotherapy. Tumors located on an outer tissue surface, e.g. esophageal tumors shrink faster than parenchymal tumors, e.g. lymph-node metastasis, because two clearance mechanisms, exfoliation and absorption, can operate in the former type of tumors whereas only absorption can function in the latter. Tumors which are being controlled do not necessarily respond completely, because tumors are constituted not only of tumor cells but also stromal tissues that are difficult to be absorbed. Long-term shrinkage patterns of a parenchymal tumor were determined by using 18 curatively irradiated hepatomas. Preoperatively irradiated thymomas (10) and lymph-node metastases (37) from head and neck cancers were examined histopathologically. Twenty-one esophageal cancers were used for intra-patient response comparison between the primary disease and the lymph-node metastases. Shrinkage patterns were generally biphasic: rapid exponential regression followed by a plateau phase. Histologically, thymomas generally consisted of predominant fibrous tissues and few remaining tumor cells. Radioresponse did not predict the presence of remaining cancer cells in the lymph nodes. Esophageal-cancer radiorespone was always higher for the primary disease than the lymph-node metastases. The location and histologic constitution of tumors must be taken into account in predicting radiocurability using radioresponse. (author)

  16. Comparison of lung tumor motion measured using a model-based 4DCT technique and a commercial protocol.

    Science.gov (United States)

    O'Connell, Dylan; Shaverdian, Narek; Kishan, Amar U; Thomas, David H; Dou, Tai H; Lewis, John H; Lamb, James M; Cao, Minsong; Tenn, Stephen; Percy, Lee P; Low, Daniel A

    2017-11-11

    To compare lung tumor motion measured with a model-based technique to commercial 4-dimensional computed tomography (4DCT) scans and describe a workflow for using model-based 4DCT as a clinical simulation protocol. Twenty patients were imaged using a model-based technique and commercial 4DCT. Tumor motion was measured on each commercial 4DCT dataset and was calculated on model-based datasets for 3 breathing amplitude percentile intervals: 5th to 85th, 5th to 95th, and 0th to 100th. Internal target volumes (ITVs) were defined on the 4DCT and 5th to 85th interval datasets and compared using Dice similarity. Images were evaluated for noise and rated by 2 radiation oncologists for artifacts. Mean differences in tumor motion magnitude between commercial and model-based images were 0.47 ± 3.0, 1.63 ± 3.17, and 5.16 ± 4.90 mm for the 5th to 85th, 5th to 95th, and 0th to 100th amplitude intervals, respectively. Dice coefficients between ITVs defined on commercial and 5th to 85th model-based images had a mean value of 0.77 ± 0.09. Single standard deviation image noise was 11.6 ± 9.6 HU in the liver and 6.8 ± 4.7 HU in the aorta for the model-based images compared with 57.7 ± 30 and 33.7 ± 15.4 for commercial 4DCT. Mean model error within the ITV regions was 1.71 ± 0.81 mm. Model-based images exhibited reduced presence of artifacts at the tumor compared with commercial images. Tumor motion measured with the model-based technique using the 5th to 85th percentile breathing amplitude interval corresponded more closely to commercial 4DCT than the 5th to 95th or 0th to 100th intervals, which showed greater motion on average. The model-based technique tended to display increased tumor motion when breathing amplitude intervals wider than 5th to 85th were used because of the influence of unusually deep inhalations. These results suggest that care must be taken in selecting the appropriate interval during image generation when using model-based 4DCT methods. Copyright © 2017

  17. A roentgenologic study of diverticular throughout the entire gastrointestinal tract

    International Nuclear Information System (INIS)

    Sohn, Myung Hee; Song, Ho Young; Lim, Kyu Yeob

    1983-01-01

    Diverticulum is considered as a common lesion involving any gastrointestinal tract from the pharynx to the rectum. We reviewed 5,806 cases of upper G-I series and 801 cases of double contrast barium enema during the period from Jan.1978 to Dec. 1981 in the Department of Radiology, School of Medicine, Jeonbug National University Hospital to analyze diverticula of the entire gastrointestinal tract. The results were as follows: 1. Roentgen examination of 5,806 esophagus, stomachs, duodenums and small bowels, and 801 colons during the past four years: diverticula of the esophagus, 60 cases (1.0%); diverticula of the stomach, 42 cases (0.7%); diverticula of the duodenum, 358 cases (6.2%); diverticula of the small bowel, 20 cases (0.3%); diverticula of the colon, 26 cases (3.2%). The location of diverticula in order of frequency was duodenum, colon, esophagus, stomach and small bowel. 2. The most common site of diverticula of each gastrointestinal tract was as follows: diverticula of the esophagus, middle portion (84.7%); diverticula of the stomach, the cardia (59.5%); diverticula of the duodenum, the second portion (81.3%); diverticula of the small bowel, the jejunum (96.4%)-especially the larger percentage were observed at the upper jejunum near the ligament of Treitz; diverticula of the colon, the right sided colon (80.8%)-the cecum and ascending colon (57.1%). 3. Diverticula may occur at any age. The majority of diverticula of the entire gastrointestinal tract were observed over 40 years of age. Especially in diverticula of the duodenum and colon, their frequency increase with age. 4. Duodenal diverticula were observed more frequently in woman than in man but in diverticula of the esophagus, stomach, small bowel and colon, male was more frequently affected. 5. The size of diverticula of the entire gastrointestinal tract was variable. The majority of diverticula of the esophagus, stomach, duodenum and small bowel were intermediate in size (10-49 mm). Diverticula of

  18. Study of Aided Diagnosis of Hepatic Carcinoma Based on Artificial Neural Network Combined with Tumor Marker Group

    Science.gov (United States)

    Tan, Shanjuan; Feng, Feifei; Wu, Yongjun; Wu, Yiming

    To develop a computer-aided diagnostic scheme by using an artificial neural network (ANN) combined with tumor markers for diagnosis of hepatic carcinoma (HCC) as a clinical assistant method. 140 serum samples (50 malignant, 40 benign and 50 normal) were analyzed for α-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), sialic acid (SA) and calcium (Ca). The five tumor marker values were then used as ANN inputs data. The result of ANN was compared with that of discriminant analysis by receiver operating characteristic (ROC) curve (AUC) analysis. The diagnostic accuracy of ANN and discriminant analysis among all samples of the test group was 95.5% and 79.3%, respectively. Analysis of multiple tumor markers based on ANN may be a better choice than the traditional statistical methods for differentiating HCC from benign or normal.

  19. A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging.

    Science.gov (United States)

    Sano, Kohei; Masuda, Ryo; Hisada, Hayato; Oishi, Shinya; Shimokawa, Kenta; Ono, Masahiro; Fujii, Nobutaka; Saji, Hideo; Mukai, Takahiro

    2014-03-01

    We have developed a novel radiogallium (Ga)-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging. A CXCR4 imaging probe with two CXCR4 antagonists (Ac-TZ14011) on Ga-DOTA core, Ga-DOTA-TZ2, was synthesized, and the affinity and binding to CXCR4 was evaluated in CXCR4 expressing cells in vitro. The affinity of Ga-DOTA-TZ2 for CXCR4 was 20-fold greater than the corresponding monovalent probe, Ga-DOTA-TZ1. (67)Ga-DOTA-TZ2 showed the significantly higher accumulation in CXCR4-expressing tumor cells compared with (67)Ga-DOTA-TZ1, suggesting the bivalent effect enhances its binding to CXCR4. The incorporation of two CXCR4 antagonists to Ga-DOTA could be effective in detecting CXCR4-expressing tumors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Testicular germinal tumors

    International Nuclear Information System (INIS)

    Fresco, R.

    2010-01-01

    This work is about diagnosis, treatment and monitoring of testicular germinal tumors. The presumed diagnosis is based in the anamnesis, clinical examination, testicular ultrasound and tumor markers. The definitive diagnosis is obtained through the inguinal radical orchidectomy

  1. Development and statistical assessment of a paper-based immunoassay for detection of tumor markers

    Energy Technology Data Exchange (ETDEWEB)

    Mazzu-Nascimento, Thiago [Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590, São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil); Morbioli, Giorgio Gianini [Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590, São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil); School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Milan, Luis Aparecido [Departamento de Estatística, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Donofrio, Fabiana Cristina [Instituto de Ciências da Saúde, Universidade Federal de Mato Grosso, 78557-267, Sinop, MT (Brazil); Mestriner, Carlos Alberto [Wama Produtos para Laboratório Ltda, 13560-971, São Carlos, SP (Brazil); Carrilho, Emanuel, E-mail: emanuel@iqsc.usp.br [Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590, São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil)

    2017-01-15

    Paper-based assays are an attractive low-cost option for clinical chemistry testing, due to characteristics such as short time of analysis, low consumption of samples and reagents, and high portability of assays. However, little attention has been given to the evaluation of the performance of these simple tests, which should include the use of a statistical approach to define the choice of best cut-off value for the test. The choice of the cut-off value impacts on the sensitivity and specificity of the bioassay. Here, we developed a paper-based immunoassay for the detection of the carcinoembryonic antigen (CEA) and performed a statistical assessment to establish the assay's cut-off value using the Youden's J index (68.28 A.U.), what allowed for a gain in sensibility (0.86) and specificity (1.0). We also discuss about the importance of defining a gray zone as a safety margin for test (±12% over the cut-off value), eliminating all false positives and false negatives outcomes and avoiding misleading results. The test accuracy was calculated as the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, presenting a value of 0.97, what classifies this test as highly accurate. We propose here a low-cost method capable of detecting carcinoembryonic antigen (CEA) in human serum samples, highlighting the importance of statistical tools to evaluate a new low-cost diagnostic method. - Highlights: • A paper-based sandwich immunoassay protocol for detection of tumor markers. • A statistical approach to define cut-off values and measuring test's sensitivity, specificity and accuracy. • A simple way to create a gray zone, avoiding false positive and false negative outcomes.

  2. A New Size-based Platform for Circulating Tumor Cell Detection in Colorectal Cancer Patients.

    Science.gov (United States)

    Oh, Bo Young; Kim, Jhingook; Lee, Woo Yong; Kim, Hee Cheol

    2017-09-01

    Circulating tumor cells (CTCs) might play a significant role in cancer progression and metastasis. However, the ability to detect CTCs is limited, especially in cells undergoing epithelial-mesenchymal transition. In this study, we evaluated a new size-based CTC detection platform and its clinical efficacy in colorectal cancer. Blood samples were obtained from 76 patients with colorectal cancer and 20 healthy control subjects for CTC analysis. CTCs were enriched using a high-density microporous chip filter and were detected using a 4-color staining protocol including 4',6-diamidino-2-phenylindole (DAPI) for nucleated cells, CD45 monoclonal antibody (mAb) as a leukocyte marker, and epithelial cell adhesion molecule (EpCAM) mAb or cytokeratin (CK) mAb as an epithelial cell marker. CTC positivity was defined as DAPI-positive (DAPI + )/CD45 - /EpCAM + or CK + cells and clinical outcomes of patients were analyzed according to CTC counts. CTCs were detected in 50 patients using this size-based filtration platform. CTC + patients were more frequently identified with a high level of carcinoembryonic antigen and advanced stage cancer (P = .038 and P = .017, respectively). CTC counts for patients with stage IV cancer (12.47 ± 24.00) were significantly higher than those for patients with cancers that were stage I to III (2.84 ± 5.29; P = .005) and healthy control subjects (0.25 ± 0.55; P colorectal cancer patients. Our results suggest that this new size-based platform has potential for determining prognosis and therapeutic response in colorectal cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Preclinical Evaluation of a Novel 177Lu- Radiopharmaceutical Based on Bombesin Structure for Prostate Tumor Diagnosis and Radionuclide Therapy

    International Nuclear Information System (INIS)

    Pujatti, P.B.; Santos, J.S.; Mengatti, J.; Araujo, E.B. de; Suzuki, M.F.; Soares, C.R.J.

    2009-01-01

    Prostate cancer is the most frequently diagnosed cancer in men in Brazil. Treatment options have varied, but once the tumor has metastasized, treatment become less effective and the cancer can progresses to a hormone refractory state characterized by high morbidity and mortality. Bombesin (BBN) receptors - in particular, the gastrin-releasing peptide (GRP) receptor - have been shown to be massively overexpressed in several human tumors types, including prostate cancer, and could be an alternative as target for its treatment by radionuclide therapy (RNT). A large number of BBN analogs had already been synthesized for this purpose and have shown to reduce tumor growth in mice. Nevertheless, most of the studied analogs exhibit high abdominal accumulation, especially in pancreas. This abdominal accumulation may represent a problem in clinical use of radiolabeled bombesin analogs probably due to serious side effects to patients. The goal of the present work was to radiolabel a novel peptide based on bombesin structure - DOTA-X-BBN(6-14), where X is a spacer of six aminoacids. - with lutetium-177, a β- emitter with optimal physical characteristics for RNT of small tumors and metastases, and to evaluate its in vitro and in vivo properties in Balb-c and Nude mice bearing prostate tumor (PC-3) xenografts. Preliminary studies were done to determine the best labeling conditions of BBNp6 and both ITLC and HPLC were applied to evaluate the radiochemical purity of the preparations. The stability of the radiolabeled peptide was assayed either after storing at 4 o C or incubation in human plasma at 37 deg. C. Biodistribution, pharmacokinetics, whole body and scintigraphic studies were performed in both healthy Balb-c and xenografted Nude mice, in order to characterize the biological properties of labeled peptide. In addition, the specificity of labeled bombesin derivative targeting to PC-3 tumor cells was analysed by in vivo competition assays. In vitro studies involved the

  4. Imaging of urinary bladder tumors

    International Nuclear Information System (INIS)

    Hadjidekov, G.

    2015-01-01

    Full text: Primary bladder neoplasms account for 2%-6% of all tumors, with urinary bladder cancer ranked as the fourth most common cancer in males. Transitional cell carcinoma (TCC) is the most common subtype of urothelial tumour accounting for approximately 90% of all urothelial cancers. It is typically observed in men aged 50-70 years with history of smoking or occupational exposure to carcinogens. Most urothelial neoplasms are low-grade papillary tumors, with high incidence of recurrence, requires rigorous follow-up but have a relatively good prognosis. Other bladder neoplasm include squamous cell carcinoma accounts for 2%-15% mainly according to geographic location; adenocarcinoma - less than 2% /both occurring in the context of chronic bladder infection and irritation/; mesenchymal tumors in 5%, with the most common examples being rhabdomyosarcoma in children and leiomyosarcoma in adults. More rare mesenchymal tumors include paraganglioma, lymphoma, leiomyoma and solitary fibrous tumor which have no specific typical imaging findings to be differentiated. Multidetector computed tomography urography is an efficient tool for diagnosis and follow-up in patients with transitional cell carcinoma and it can be considered the primary radiologic method for detection, staging and assessment of the entire urothelium regarding the multicentric nature of TCC. MRI is rapidly expanding modality of choice especially in locally staging the tumor and in controversies. Accurate TNM staging is primordial in choosing treatment and prognosis for patients with bladder carcinoma. Correct interpretation and classification of the tumour is helpful for the urologists to determine further management in these cases. The learning objectives of the presentation are: to illustrate the spectrum of CT and MRI findings and to assess their clinical value in patients with transitional cell carcinoma and some other bladder neoplasm; to discuss the TNM staging based on the imaging findings; to be

  5. Content-based image retrieval using spatial layout information in brain tumor T1-weighted contrast-enhanced MR images.

    Science.gov (United States)

    Huang, Meiyan; Yang, Wei; Wu, Yao; Jiang, Jun; Gao, Yang; Chen, Yang; Feng, Qianjin; Chen, Wufan; Lu, Zhentai

    2014-01-01

    This study aims to develop content-based image retrieval (CBIR) system for the retrieval of T1-weighted contrast-enhanced MR (CE-MR) images of brain tumors. When a tumor region is fed to the CBIR system as a query, the system attempts to retrieve tumors of the same pathological category. The bag-of-visual-words (BoVW) model with partition learning is incorporated into the system to extract informative features for representing the image contents. Furthermore, a distance metric learning algorithm called the Rank Error-based Metric Learning (REML) is proposed to reduce the semantic gap between low-level visual features and high-level semantic concepts. The effectiveness of the proposed method is evaluated on a brain T1-weighted CE-MR dataset with three types of brain tumors (i.e., meningioma, glioma, and pituitary tumor). Using the BoVW model with partition learning, the mean average precision (mAP) of retrieval increases beyond 4.6% with the learned distance metrics compared with the spatial pyramid BoVW method. The distance metric learned by REML significantly outperforms three other existing distance metric learning methods in terms of mAP. The mAP of the CBIR system is as high as 91.8% using the proposed method, and the precision can reach 93.1% when the top 10 images are returned by the system. These preliminary results demonstrate that the proposed method is effective and feasible for the retrieval of brain tumors in T1-weighted CE-MR Images.

  6. Content-based image retrieval using spatial layout information in brain tumor T1-weighted contrast-enhanced MR images.

    Directory of Open Access Journals (Sweden)

    Meiyan Huang

    Full Text Available This study aims to develop content-based image retrieval (CBIR system for the retrieval of T1-weighted contrast-enhanced MR (CE-MR images of brain tumors. When a tumor region is fed to the CBIR system as a query, the system attempts to retrieve tumors of the same pathological category. The bag-of-visual-words (BoVW model with partition learning is incorporated into the system to extract informative features for representing the image contents. Furthermore, a distance metric learning algorithm called the Rank Error-based Metric Learning (REML is proposed to reduce the semantic gap between low-level visual features and high-level semantic concepts. The effectiveness of the proposed method is evaluated on a brain T1-weighted CE-MR dataset with three types of brain tumors (i.e., meningioma, glioma, and pituitary tumor. Using the BoVW model with partition learning, the mean average precision (mAP of retrieval increases beyond 4.6% with the learned distance metrics compared with the spatial pyramid BoVW method. The distance metric learned by REML significantly outperforms three other existing distance metric learning methods in terms of mAP. The mAP of the CBIR system is as high as 91.8% using the proposed method, and the precision can reach 93.1% when the top 10 images are returned by the system. These preliminary results demonstrate that the proposed method is effective and feasible for the retrieval of brain tumors in T1-weighted CE-MR Images.

  7. Improved in vivo gene transfer into tumor tissue by stabilization of pseudodendritic oligoethylenimine-based polyplexes.

    Science.gov (United States)

    Russ, Verena; Fröhlich, Thomas; Li, Yunqiu; Halama, Anna; Ogris, Manfred; Wagner, Ernst

    2010-02-01

    HD O is a low molecular weight pseudodendrimer containing oligoethylenimine and degradable hexanediol diacrylate diesters. DNA polyplexes display encouraging gene transfer efficiency in vitro and in vivo but also a limited stability under physiological conditions. This limitation must be overcome for further development into more sophisticated formulations. HD O polyplexes were laterally stabilized by crosslinking surface amines via bifunctional crosslinkers, bioreducible dithiobis(succimidyl propionate) (DSP) or the nonreducible analog disuccinimidyl suberate (DSS). Optionally, in a subsequent step, the targeting ligand transferrin (Tf) was attached to DSP-linked HD O polyplexes via Schiff base formation between HD O amino groups and Tf aldehyde groups, which were introduced into Tf by periodate oxidation of the glycosylation sites. Crosslinked DNA polyplexes showed an increased stability against exchange reaction by salt or heparin. Disulfide bond containing DSP-linked polyplexes were susceptible to reducing conditions. These polyplexes displayed the highest gene expression levels in vitro and in vivo (upon intratumoral application in mice), and these were significantly elevated and prolonged over standard or DSS-stabilized HD O formulations. DSP-stabilized HD O polyplexes with or without Tf coating were well-tolerated after intravenous application. High gene expression levels were found in tumor tissue, with negligible gene expression in any other organ. Lateral stabilization of HD O polyplexes with DSP crosslinker enhanced gene transfer efficacy and was essential for the incorporation of a ligand (Tf) into a stable particle formulation.

  8. Fabrication of a two-level tumor bone repair biomaterial based on a rapid prototyping technique

    Energy Technology Data Exchange (ETDEWEB)

    Kai He; Yan Yongnian; Zhang Renji; Wang Xiaohong [Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Wang Xinluan; Madhukar, Kumta Shekhar; Qin Ling [Department of Orthoapedics and Traumatology, The Chinese University of Hong Kong. Shatin, NT (Hong Kong)], E-mail: wangxiaohong@tsinghua.edu.cn, E-mail: kumta@cuhk.edu.hk, E-mail: qin@ort.cuhk.edu.hk

    2009-06-01

    After the removal of the giant cell tumor (GCT) of bone, it is necessary to fill the defects with adequate biomaterials. A new functional bone repair material with both stimulating osteoblast growth and inhibiting osteoclast activity has been developed with phosphorylated chitosan (P-chitosan) and disodium (1 {yields} 4)-2-deoxy-2-sulfoamino-{beta}-D-glucopyranuronan (S-chitosan) as the additives of poly(lactic acid-co-glycolic acid) (PLGA)/calcium phosphate (TCP) scaffolds based on a double-nozzle low-temperature deposition manufacturing technique. A computer-assisted design model was used and the optimal fabrication parameters were determined through the manipulation of a pure PLGA/TCP system. The microscopic structures, water absorbability and mechanical properties of the samples with different P-chitosan and S-chitosan concentrations were characterized correspondingly. The results suggested that this unique composite porous scaffold material is a potential candidate for the repair of large bone defects after a surgical removal of GCT.

  9. Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms’ Tumor 1 in Patients with Advanced Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Shigetaka Shimodaira

    2015-12-01

    Full Text Available Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms’ tumor (WT1 class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1–2 × 107 DCs with 1–2 KE of OK-432 (streptococcal preparation in three patients. Clinical efficacy was confirmed based on WT1 expression using immunohistochemistry on paraffin-embedded tissues and immune monitoring using tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT assays. WT1 expression with human leukocyte antigen (HLA-class I molecules was detected in surgical resected tissues. Adverse reactions to DC vaccinations were tolerable under an adjuvant setting. WT1-specific cytotoxic T cells were detected by both modified WT1-peptide/HLA-A*24:02 tetramer analysis and/or interferon-γ-producing cells through the use of ELISPOT assays after the first DC vaccination. Immunity acquired from DC vaccination persisted for two years with prolonged disease-free and overall survival. The present study indicated that DC vaccination targeting WT1 demonstrated the safety and immunogenicity as an adjuvant therapy in patients with resectable advanced colorectal cancer.

  10. Velocity effect on aptamer-based circulating tumor cell isolation in microfluidic devices.

    Science.gov (United States)

    Wan, Yuan; Tan, Jifu; Asghar, Waseem; Kim, Young-tae; Liu, Yaling; Iqbal, Samir M

    2011-12-01

    The isolation and detection of rare circulating tumor cells (CTCs) has been one of the focuses of intense research recently. In a microfluidic device, a number of factors can influence the enrichment capability of surface-bound probe molecules. This article analyzes the important factor of flow velocity in a microfluidic channel. The competition of surface-grafted anti-EGFR aptamers to bind the overexpressed EGFR on cell membranes against the drag force from the fluid flow is an important efficiency determining factor. The flow rate variations are applied both in experiments and in simulation models to study their effects on CTC capture efficiency. A mixture of mononuclear cells and human Glioblastoma cells is used to isolate cancer cells from the cellular flow. The results show interdependence between the adhesion probability, isolation efficiency, and flow rate. This work can help in designing flow-through lab-on-chip devices that use surface-bound probe affinities against overexpressed biomarkers for cell isolation. This work demonstrates that microfluidic based approaches have strong potential applications in CTC detection and isolation. © 2011 American Chemical Society

  11. Stimuli-Responsive Nanodiamond-Based Biosensor for Enhanced Metastatic Tumor Site Detection.

    Science.gov (United States)

    Wang, Xin; Gu, Mengjie; Toh, Tan Boon; Abdullah, Nurrul Lissa Binti; Chow, Edward Kai-Hua

    2018-02-01

    Metastasis is often critical to cancer progression and linked to poor survival and drug resistance. Early detection of metastasis, as well as identification of metastatic tumor sites, can improve cancer patient survival. Thus, developing technology to improve the detection of cancer metastasis biomarkers can improve both diagnosis and treatment. In this study, we investigated the use of nanodiamonds to develop a stimuli-responsive metastasis detection complex that utilizes matrix metalloproteinase 9 (MMP9) as a metastasis biomarker, as MMP9 increased expression has been shown to be indicative of metastasis. The nanodiamond-MMP9 biosensor complex consists of nanodiamonds functionalized with MMP9-specific fluorescent-labeled substrate peptides. Using this design, protease activity of MMP9 can be accurately measured and correlated to MMP9 expression. The nanodiamond-MMP9 biosensor also demonstrated an enhanced ability to protect the base sensor peptide from nonspecific serum protease cleavage. This enhanced peptide stability, combined with a quantitative stimuli-responsive output function, provides strong evidence for the further development of a nanodiamond-MMP9 biosensor for metastasis site detection. More importantly, this work provides the foundation for use of nanodiamonds as a platform for stimuli-responsive biosensors and theranostic complexes that can be implemented across a wide range of biomedical applications.

  12. MR Imaging with Gadolinium-DTPA in skull-base tumors

    International Nuclear Information System (INIS)

    Bartolozzi, C.; Olmastroni, M.; Dal Pozzo, G.; Petacchi, D.

    1988-01-01

    Twenty-five patients were investigated by MR imaging in order to evaluate the diagnostic value of Gadolinium (Gd)-DTPA in skull-base tumors. The patients were studied with standard acquisition techniques (T1, mixed and T2-weighted images) without contrast medium. The images obtained after intravenous injection of Gd-DTPA. The contrastographic results in the different types of acquisition were evaluated. Thanks to the extra-ordinary increase in contrast resolution it provides, Gd-DTPA allowed the precise evaluation of the lesion and of its perfect spatial definition in all cases. Our experience demonstrated that Gd-DTPA considerably increases the sensitivity of the technique in this anatomical region. On the contrary, as regards the nature of the lesion, the signal did not significantly very after the iv injection of Gd-DTPA in the various kinds of lesion. In addition to the important diagnostic advantages of Gd-DTPA, its excellent tollerability and the absence of side-effects must be stressed

  13. Tumor immunology.

    Science.gov (United States)

    Mocellin, Simone; Lise, Mario; Nitti, Donato

    2007-01-01

    Advances in tumor immunology are supporting the clinical implementation of several immunological approaches to cancer in the clinical setting. However, the alternate success of current immunotherapeutic regimens underscores the fact that the molecular mechanisms underlying immune-mediated tumor rejection are still poorly understood. Given the complexity of the immune system network and the multidimensionality of tumor/host interactions, the comprehension of tumor immunology might greatly benefit from high-throughput microarray analysis, which can portrait the molecular kinetics of immune response on a genome-wide scale, thus accelerating the discovery pace and ultimately catalyzing the development of new hypotheses in cell biology. Although in its infancy, the implementation of microarray technology in tumor immunology studies has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to an effective immune response against cancer. Although the general principles of microarray-based gene profiling have rapidly spread in the scientific community, the need for mastering this technique to produce meaningful data and correctly interpret the enormous output of information generated by this technology is critical and represents a tremendous challenge for investigators, as outlined in the first section of this book. In the present Chapter, we report on some of the most significant results obtained with the application of DNA microarray in this oncology field.

  14. Bone tumors

    International Nuclear Information System (INIS)

    Unni, K.K.

    1988-01-01

    This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

  15. Real-time tumor ablation simulation based on the dynamic mode decomposition method

    KAUST Repository

    Bourantas, George C.; Ghommem, Mehdi; Kagadis, George C.; Katsanos, Konstantinos H.; Loukopoulos, Vassilios C.; Burganos, Vasilis N.; Nikiforidis, George C.

    2014-01-01

    Purpose: The dynamic mode decomposition (DMD) method is used to provide a reliable forecasting of tumor ablation treatment simulation in real time, which is quite needed in medical practice. To achieve this, an extended Pennes bioheat model must

  16. New method for extracting tumors in PET/CT images based on the probability distribution

    International Nuclear Information System (INIS)

    Nitta, Shuhei; Hontani, Hidekata; Hukami, Tadanori

    2006-01-01

    In this report, we propose a method for extracting tumors from PET/CT images by referring to the probability distribution of pixel values in the PET image. In the proposed method, first, the organs that normally take up fluorodeoxyglucose (FDG) (e.g., the liver, kidneys, and brain) are extracted. Then, the tumors are extracted from the images. The distribution of pixel values in PET images differs in each region of the body. Therefore, the threshold for detecting tumors is adaptively determined by referring to the distribution. We applied the proposed method to 37 cases and evaluated its performance. This report also presents the results of experiments comparing the proposed method and another method in which the pixel values are normalized for extracting tumors. (author)

  17. A review of nasal, paranasal, and skull base tumors invading the orbit

    DEFF Research Database (Denmark)

    Jørgensen, Morten; Heegaard, Steffen

    2018-01-01

    of ophthalmological and otorhinolaryngological symptoms, including proptosis, pain, decreased visual acuity, restrictions in motility of the eye, epistaxis, and nasal obstruction. Sarcomas and benign bone and cartilage tumors arise from surrounding structures, whereas carcinomas usually arise from the paranasal...

  18. Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

    Science.gov (United States)

    Diaz-Cano, Salvador J.

    2012-01-01

    Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma), mechanisms of intercellular transference of genetic information (exosomes), and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning. PMID:22408433

  19. Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

    Directory of Open Access Journals (Sweden)

    Salvador J. Diaz-Cano

    2012-02-01

    Full Text Available Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma, mechanisms of intercellular transference of genetic information (exosomes, and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning.

  20. Lipid nanocarriers based on natural oils with high activity against oxygen free radicals and tumor cell proliferation

    International Nuclear Information System (INIS)

    Lacatusu, I.; Badea, N.; Badea, G.; Oprea, O.; Mihaila, M.A.; Kaya, D.A.; Stan, R.; Meghea, A.

    2015-01-01

    The development of nano-dosage forms of phytochemicals represents a significant progress of the scientific approach in the biomedical research. The aim of this study was to assess the effectiveness of lipid nanocarriers based on natural oils (grape seed oil, fish oil and laurel leaf oil) in counteracting free radicals and combating certain tumor cells. No drug was encapsulated in the nanocarriers. The cytotoxic effect exerted by bioactive nanocarriers against two tumor cells, MDA-MB 231 and HeLa cell lines, and two normal cells, L929 and B16 cell lines, was measured using the MTT assay, while oxidative damage was assessed by measuring the total antioxidant activity using chemiluminescence analysis. The best performance was obtained for nanocarriers based on an association of grape seed and laurel leaf oils, with a capacity to scavenge about 98% oxygen free radicals. A dose of nanocarriers of 5 mg·mL −1 has led to a drastic decrease in tumor cell proliferation even in the absence of an antitumor drug (e.g. about 50% viability for MDA-MB 231 cell line and 60% viability for HeLa cell line). A comparative survival profile of normal and tumor cells, which were exposed to an effective dose of 2.5 mg·mL −1 lipid nanocarriers, has revealed a death rate of 20% for normal B16 cells and of 40% death rate for MDA-MB 231 and HeLa tumor cells. The results in this study imply that lipid nanocarriers based on grape seed oil in association with laurel leaf oil could be a candidate to reduce the delivery system toxicity and may significantly improve the therapeutic efficacy of antitumor drugs in clinical applications. - Highlights: • Functional lipid nanocarriers with unique features and broad spectrum effectiveness • Lipid nanocarriers based on laureal leaf oil (LLO) and grape seed oil (GSO) • Antioxidant activity has reached 98% for nanocarriers containing 25% GSO and 2% LLO. • LLO exerts a significant cytotoxic effect against HeLa and MDA-MB 231 tumor cells. • 50

  1. Lipid nanocarriers based on natural oils with high activity against oxygen free radicals and tumor cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Lacatusu, I.; Badea, N.; Badea, G.; Oprea, O. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania); Mihaila, M.A. [Institute of Virusology “Stefan S. Nicolau”, Center of Immunology, Bravu Road, No. 285, 030304 Bucharest (Romania); Kaya, D.A. [Department of Field Crops, Faculty of Agriculture, Mustafa Kemal University, 31030 Antakya, Hatay (Turkey); Stan, R., E-mail: rl_stan2000@yahoo.com [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania); Meghea, A. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania)

    2015-11-01

    The development of nano-dosage forms of phytochemicals represents a significant progress of the scientific approach in the biomedical research. The aim of this study was to assess the effectiveness of lipid nanocarriers based on natural oils (grape seed oil, fish oil and laurel leaf oil) in counteracting free radicals and combating certain tumor cells. No drug was encapsulated in the nanocarriers. The cytotoxic effect exerted by bioactive nanocarriers against two tumor cells, MDA-MB 231 and HeLa cell lines, and two normal cells, L929 and B16 cell lines, was measured using the MTT assay, while oxidative damage was assessed by measuring the total antioxidant activity using chemiluminescence analysis. The best performance was obtained for nanocarriers based on an association of grape seed and laurel leaf oils, with a capacity to scavenge about 98% oxygen free radicals. A dose of nanocarriers of 5 mg·mL{sup −1} has led to a drastic decrease in tumor cell proliferation even in the absence of an antitumor drug (e.g. about 50% viability for MDA-MB 231 cell line and 60% viability for HeLa cell line). A comparative survival profile of normal and tumor cells, which were exposed to an effective dose of 2.5 mg·mL{sup −1} lipid nanocarriers, has revealed a death rate of 20% for normal B16 cells and of 40% death rate for MDA-MB 231 and HeLa tumor cells. The results in this study imply that lipid nanocarriers based on grape seed oil in association with laurel leaf oil could be a candidate to reduce the delivery system toxicity and may significantly improve the therapeutic efficacy of antitumor drugs in clinical applications. - Highlights: • Functional lipid nanocarriers with unique features and broad spectrum effectiveness • Lipid nanocarriers based on laureal leaf oil (LLO) and grape seed oil (GSO) • Antioxidant activity has reached 98% for nanocarriers containing 25% GSO and 2% LLO. • LLO exerts a significant cytotoxic effect against HeLa and MDA-MB 231 tumor

  2. A conceptual design of neutron tumor therapy reactor facility with a YAYOI based fast neutron source reactor

    International Nuclear Information System (INIS)

    Wakabayashi, Hiroaki; An, Shigehiro.

    1983-01-01

    Fast neutron is known as one of useful radiations for radiation therapy of tumors. Boron neutron capture therapy (BNCT) of tumors which makes use of 10 B(n, α) 7 Li reaction of 10 B compounds selectively attached to tumor cells with thermal and intermediate neutrons is another way of neutron based radiation therapy which is, above all, attractive enough to kill tumor cells selectively sparing normal tissue. In Japan, BNCT has already been applied and leaned to be effective. After more than a decade operational experiences and the specific experiments designed for therapeutical purposes, in this paper, a conceptual design of a special neutron therapy reactor facility based on YAYOI - fast neutron source reactor of Nuclear Engineering Research Laboratory, Faculty of Engineering, the University of Tokyo - modified to provide an upward beam of fast and intermediate neutrons is presented. Emphasis is placed on the in-house nature of facility and on the coordinating capability of biological and physical researches as well as maintenances of the facility. (author)

  3. Targeting carbonic anhydrase IX by nitroimidazole based sulfamides enhances the therapeutic effect of tumor irradiation: A new concept of dual targeting drugs

    International Nuclear Information System (INIS)

    Dubois, Ludwig; Peeters, Sarah G.J.A.; Kuijk, Simon J.A. van; Yaromina, Ala; Lieuwes, Natasja G.; Saraya, Ruchi; Biemans, Rianne; Rami, Marouan; Parvathaneni, Nanda Kumar; Vullo, Daniela; Vooijs, Marc; Supuran, Claudiu T.; Winum, Jean-Yves

    2013-01-01

    Background and purpose: Carbonic anhydrase IX (CAIX) plays an important role in pH regulation processes critical for tumor cell growth and metastasis. We hypothesize that a dual targeting bioreductive nitroimidazole based anti-CAIX sulfamide drug (DH348) will reduce tumor growth and sensitize tumors to irradiation in a CAIX dependent manner. Material and methods: The effect of the dual targeting anti-CAIX (DH348) and its single targeting control drugs on extracellular acidification and radiosensitivity was examined in HT-29 colorectal carcinoma cells. Tumor growth and time to reach 4× start volume (T4×SV) was monitored for animals receiving DH348 (10 mg/kg) combined with tumor single dose irradiation (10 Gy). Results: In vitro, DH348 reduced hypoxia-induced extracellular acidosis, but did not change hypoxic radiosensitivity. In vivo, DH348 monotherapy decreased tumor growth rate and sensitized tumors to radiation (enhancement ratio 1.50) without systemic toxicity only for CAIX expressing tumors. Conclusions: A newly designed nitroimidazole and sulfamide dual targeting drug reduces hypoxic extracellular acidification, slows down tumor growth at nontoxic doses and sensitizes tumors to irradiation all in a CAIX dependent manner, suggesting no “off-target” effects. Our data therefore indicate the potential utility of a dual drug approach as a new strategy for tumor-specific targeting

  4. Brown tumors of the anterior skull base as the initial manifestation of true normocalcemic primary hyperparathyroidism: report of three cases and review of the literature.

    Science.gov (United States)

    Khalatbari, Mahmoud Reza; Hamidi, Mehrdokht; Moharamzad, Yashar; Setayesh, Ali; Amirjamshidi, Abbas

    2013-01-01

    Brown tumor is a bone lesion secondary to hyperparathyroidism of various etiologies. Skeletal involvement in primary hyperparathyroidism secondary to parathyroid adenoma is very uncommon and brown tumor has become extremely a rare clinical entity. Hyperparathyroidism is usually associated with high levels of serum calcium. Brown tumor as the only and initial symptom of normocalcemic primary hyperparathyroidism is extremely rare. Moreover, involvement of the skull base and the orbit is exceedingly rare. The authors would report three cases of brown tumor of the anterior skull base that were associated with true normocalcemic primary hyperparathyroidism. Clinical manifestations, neuroimaging findings, pathological findings, diagnosis and treatment of the patients are discussed and the relevant literature is reviewed.

  5. No turnover in lens lipids for the entire human lifespan.

    Science.gov (United States)

    Hughes, Jessica R; Levchenko, Vladimir A; Blanksby, Stephen J; Mitchell, Todd W; Williams, Alan; Truscott, Roger J W

    2015-03-11

    Lipids are critical to cellular function and it is generally accepted that lipid turnover is rapid and dysregulation in turnover results in disease (Dawidowicz 1987; Phillips et al., 2009; Liu et al., 2013). In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan. This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable. Such substantial changes in lens cell membranes may play a role in the genesis of age-related eye disorders. Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases.

  6. Waste management aspects of entire PWR LOOP decontamination

    International Nuclear Information System (INIS)

    Murray, A.P.; Roesmer, J.

    1988-01-01

    The waste management parameters for decontamination of an entire PWR primary circuit have been determined for dilute alkaline-permanganate/citric acid (APCA), LOMI, ozone and cerium acid process variations. APCA processes generate the largest waste volumes; over 140 m 3 (5000 ft 3 ) in some cases. This represents a potential disposal cost of one million dollars. The cation regeneration column makes the greatest contribution to the disposal volume. In contrast, the LOMI process generates approximately half as much waste, but it is expected to contain relatively high metal concentrations (200-800 ppm). The ozone and cerium acid processes product the least waste, usually under 45 m 3 . These waste volume estimates represent considerable fractions of a utility's annual disposal volume. Consequently, improved waste processing technology is required, and several approaches are suggested

  7. Phosphotyrosine-based-phosphoproteomics scaled-down to biopsy level for analysis of individual tumor biology and treatment selection.

    Science.gov (United States)

    Labots, Mariette; van der Mijn, Johannes C; Beekhof, Robin; Piersma, Sander R; de Goeij-de Haas, Richard R; Pham, Thang V; Knol, Jaco C; Dekker, Henk; van Grieken, Nicole C T; Verheul, Henk M W; Jiménez, Connie R

    2017-06-06

    Mass spectrometry-based phosphoproteomics of cancer cell and tissue lysates provides insight in aberrantly activated signaling pathways and potential drug targets. For improved understanding of individual patient's tumor biology and to allow selection of tyrosine kinase inhibitors in individual patients, phosphoproteomics of small clinical samples should be feasible and reproducible. We aimed to scale down a pTyr-phosphopeptide enrichment protocol to biopsy-level protein input and assess reproducibility and applicability to tumor needle biopsies. To this end, phosphopeptide immunoprecipitation using anti-phosphotyrosine beads was performed using 10, 5 and 1mg protein input from lysates of colorectal cancer (CRC) cell line HCT116. Multiple needle biopsies from 7 human CRC resection specimens were analyzed at the 1mg-level. The total number of phosphopeptides captured and detected by LC-MS/MS ranged from 681 at 10mg input to 471 at 1mg HCT116 protein. ID-reproducibility ranged from 60.5% at 10mg to 43.9% at 1mg. Per 1mg-level biopsy sample, >200 phosphopeptides were identified with 57% ID-reproducibility between paired tumor biopsies. Unsupervised analysis clustered biopsies from individual patients together and revealed known and potential therapeutic targets. This study demonstrates the feasibility of label-free pTyr-phosphoproteomics at the tumor biopsy level based on reproducible analyses using 1mg of protein input. The considerable number of identified phosphopeptides at this level is attributed to an effective down-scaled immuno-affinity protocol as well as to the application of ID propagation in the data processing and analysis steps. Unsupervised cluster analysis reveals patient-specific profiles. Together, these findings pave the way for clinical trials in which pTyr-phosphoproteomics will be performed on pre- and on-treatment biopsies. Such studies will improve our understanding of individual tumor biology and may enable future pTyr-phosphoproteomics-based

  8. Birth characteristics and Wilms tumors in children in the Nordic countries: a register-based case-control study.

    Science.gov (United States)

    Schüz, Joachim; Schmidt, Lisbeth Samsø; Kogner, Per; Lähteenmäki, Päivi M; Pal, Niklas; Stokland, Tore; Schmiegelow, Kjeld

    2011-05-01

    Little is known about causes of Wilms tumor. Because of the young age at diagnosis, several studies have looked at various birth characteristics. We conducted a registry-based case-control study involving 690 cases of Wilms tumor aged 0-14 years, occurring in Denmark, Finland, Norway or Sweden during 1985-2006, individually matched to five controls drawn randomly from the Nordic childhood population. Information on birth characteristics was obtained from the population-based medical birth registries. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis. We observed a distinct association between Wilms tumor and high birth weight (≥4 kg) for girls (OR 1.97, CI 1.50-2.59) but not for boys (1.04, 0.78-1.38); overall, the OR was 1.43 (1.17-1.74). Among girls, risk increased by 28% (15-42%) per 500 g increase in birth weight. Large-for-gestational age girls also had a higher risk (2.48, 1.51-4.05), whereas no effect was seen for boys (1.12, 0.60-2.07). An association was seen with Apgar score at 5 min birth order. In our large-scale, registry-based study, we confirmed earlier observations of an association between high birth weight and risk of Wilms tumor, but we found an effect only in girls. The higher risk of infants with low Apgar score might reflect hypoxia causing cell damage, adverse side effects of neonatal treatment or reverse causation as low Apgar score might indicate the presence of a tumor. Copyright © 2010 UICC.

  9. Real-time tumor ablation simulation based on the dynamic mode decomposition method

    KAUST Repository

    Bourantas, George C.

    2014-05-01

    Purpose: The dynamic mode decomposition (DMD) method is used to provide a reliable forecasting of tumor ablation treatment simulation in real time, which is quite needed in medical practice. To achieve this, an extended Pennes bioheat model must be employed, taking into account both the water evaporation phenomenon and the tissue damage during tumor ablation. Methods: A meshless point collocation solver is used for the numerical solution of the governing equations. The results obtained are used by the DMD method for forecasting the numerical solution faster than the meshless solver. The procedure is first validated against analytical and numerical predictions for simple problems. The DMD method is then applied to three-dimensional simulations that involve modeling of tumor ablation and account for metabolic heat generation, blood perfusion, and heat ablation using realistic values for the various parameters. Results: The present method offers very fast numerical solution to bioheat transfer, which is of clinical significance in medical practice. It also sidesteps the mathematical treatment of boundaries between tumor and healthy tissue, which is usually a tedious procedure with some inevitable degree of approximation. The DMD method provides excellent predictions of the temperature profile in tumors and in the healthy parts of the tissue, for linear and nonlinear thermal properties of the tissue. Conclusions: The low computational cost renders the use of DMD suitable forin situ real time tumor ablation simulations without sacrificing accuracy. In such a way, the tumor ablation treatment planning is feasible using just a personal computer thanks to the simplicity of the numerical procedure used. The geometrical data can be provided directly by medical image modalities used in everyday practice. © 2014 American Association of Physicists in Medicine.

  10. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model.

    Directory of Open Access Journals (Sweden)

    Stine Skov Jensen

    Full Text Available Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking invasion and tumor stemness into account.Glioblastoma stem cell-like containing spheroid (GSS cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models.We observed a pronounced invasion into brain slice cultures both by confocal time-lapse microscopy and immunohistochemistry. This invasion closely resembled the invasion in vivo. The Ki-67 proliferation indexes in spheroids implanted into brain slices were lower than in free-floating spheroids. The expression of stem cell markers varied between free-floating spheroids, spheroids implanted into brain slices and tumors in vivo.The established invasion model kept in stem cell medium closely mimics tumor cell invasion into the brain in vivo preserving also to some extent the expression of stem cell markers. The model is feasible and robust and we suggest the model as an in vivo-like model with a great potential in glioma studies and drug discovery.

  11. Tumor endothelium marker-8 based decoys exhibit superiority over capillary morphogenesis protein-2 based decoys as anthrax toxin inhibitors.

    Directory of Open Access Journals (Sweden)

    Chenguang Cai

    Full Text Available Anthrax toxin is the major virulence factor produced by Bacillus anthracis. The toxin consists of three protein subunits: protective antigen (PA, lethal factor, and edema factor. Inhibition of PA binding to its receptors, tumor endothelium marker-8 (TEM8 and capillary morphogenesis protein-2 (CMG2 can effectively block anthrax intoxication, which is particularly valuable when the toxin has already been overproduced at the late stage of anthrax infection, thus rendering antibiotics ineffectual. Receptor-like agonists, such as the mammalian cell-expressed von Willebrand factor type A (vWA domain of CMG2 (sCMG2, have demonstrated potency against the anthrax toxin. However, the soluble vWA domain of TEM8 (sTEM8 was ruled out as an anthrax toxin inhibitor candidate due to its inferior affinity to PA. In the present study, we report that L56A, a PA-binding-affinity-elevated mutant of sTEM8, could inhibit anthrax intoxication as effectively as sCMG2 in Fisher 344 rats. Additionally, pharmacokinetics showed that L56A and sTEM8 exhibit advantages over sCMG2 with better lung-targeting and longer plasma retention time, which may contribute to their enhanced protective ability in vivo. Our results suggest that receptor decoys based on TEM8 are promising anthrax toxin inhibitors and, together with the pharmacokinetic studies in this report, may contribute to the development of novel anthrax drugs.

  12. Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain

    Science.gov (United States)

    2014-01-01

    Introduction Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. Methods We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd’s scale and was conflated into: 75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Results Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; screening-detected cancers, extreme breast density

  13. Impact of muscular uptake and statistical noise on tumor quantification based on simulated FDG-PET studies

    International Nuclear Information System (INIS)

    Silva-Rodríguez, Jesús; Domínguez-Prado, Inés; Pardo-Montero, Juan; Ruibal, Álvaro

    2017-01-01

    Purpose: The aim of this work is to study the effect of physiological muscular uptake variations and statistical noise on tumor quantification in FDG-PET studies. Methods: We designed a realistic framework based on simulated FDG-PET acquisitions from an anthropomorphic phantom that included different muscular uptake levels and three spherical lung lesions with diameters of 31, 21 and 9 mm. A distribution of muscular uptake levels was obtained from 136 patients remitted to our center for whole-body FDG-PET. Simulated FDG-PET acquisitions were obtained by using the Simulation System for Emission Tomography package (SimSET) Monte Carlo package. Simulated data was reconstructed by using an iterative Ordered Subset Expectation Maximization (OSEM) algorithm implemented in the Software for Tomographic Image Reconstruction (STIR) library. Tumor quantification was carried out by using estimations of SUV max , SUV 50 and SUV mean from different noise realizations, lung lesions and multiple muscular uptakes. Results: Our analysis provided quantification variability values of 17–22% (SUV max ), 11–19% (SUV 50 ) and 8–10% (SUV mean ) when muscular uptake variations and statistical noise were included. Meanwhile, quantification variability due only to statistical noise was 7–8% (SUV max ), 3–7% (SUV 50 ) and 1–2% (SUV mean ) for large tumors (>20 mm) and 13% (SUV max ), 16% (SUV 50 ) and 8% (SUV mean ) for small tumors (<10 mm), thus showing that the variability in tumor quantification is mainly affected by muscular uptake variations when large enough tumors are considered. In addition, our results showed that quantification variability is strongly dominated by statistical noise when the injected dose decreases below 222 MBq. Conclusions: Our study revealed that muscular uptake variations between patients who are totally relaxed should be considered as an uncertainty source of tumor quantification values. - Highlights: • Distribution of muscular uptake from 136 PET

  14. Tumor Classification Using High-Order Gene Expression Profiles Based on Multilinear ICA

    Directory of Open Access Journals (Sweden)

    Ming-gang Du

    2009-01-01

    Full Text Available Motivation. Independent Components Analysis (ICA maximizes the statistical independence of the representational components of a training gene expression profiles (GEP ensemble, but it cannot distinguish relations between the different factors, or different modes, and it is not available to high-order GEP Data Mining. In order to generalize ICA, we introduce Multilinear-ICA and apply it to tumor classification using high order GEP. Firstly, we introduce the basis conceptions and operations of tensor and recommend Support Vector Machine (SVM classifier and Multilinear-ICA. Secondly, the higher score genes of original high order GEP are selected by using t-statistics and tabulate tensors. Thirdly, the tensors are performed by Multilinear-ICA. Finally, the SVM is used to classify the tumor subtypes. Results. To show the validity of the proposed method, we apply it to tumor classification using high order GEP. Though we only use three datasets, the experimental results show that the method is effective and feasible. Through this survey, we hope to gain some insight into the problem of high order GEP tumor classification, in aid of further developing more effective tumor classification algorithms.

  15. Residual motion of lung tumors in end-of-inhale respiratory gated radiotherapy based on external surrogates

    International Nuclear Information System (INIS)

    Berbeco, Ross I.; Nishioka, Seiko; Shirato, Hiroki; Jiang, Steve B.

    2006-01-01

    It has been noted that some lung tumors exhibit large periodic motion due to respiration. To limit the amount of dose to healthy lung tissues, many clinics have begun gating radiotherapy treatment using externally placed surrogates. It has been observed by several institutions that the end-of-exhale (EOE) tumor position is more reproducible than other phases of the breathing cycle, so the gating window is often set there. From a treatment planning perspective, end-of-inhale (EOI) phase might be preferred for gating because the expanded lungs will further decrease the healthy tissue within the treatment field. We simulate gated treatment at the EOI phase, using a set of recently measured internal/external anatomy patient data. This paper attempts to answer three questions: (1) How much is the tumor residual motion when we use an external surrogate gating window at EOI? (2) How could we reduce the residual motion in the EOI gating window? (3) Is there a preference for amplitude- versus phase-based gating at EOI? We found that under free breathing conditions the residual motion of the tumors is much larger for EOI phase than for EOE phase. The mean values of residual motion at EOI were found to be 2.2 and 2.7 mm for amplitude- and phase-based gating, respectively, and, at EOE, 1.0 and 1.2 mm for amplitude- and phase-based gating, respectively. However, we note that the residual motion in the EOI gating window is correlated well with the reproducibility of the external surface position in the EOI phase. Using the results of a published breath-coaching study, we deduce that the residual motion of a lung tumor at EOI would approach that at EOE, with the same duty cycle (30%), under breath-coaching conditions. Additionally, we found that under these same conditions, phase-based gating approaches the same residual motion as amplitude-based gating, going from a 28% difference to 11%, for the patient with the largest difference between the two gating modalities. We conclude

  16. Prognostic factors in breast phyllodes tumors: a nomogram based on a retrospective cohort study of 404 patients.

    Science.gov (United States)

    Zhou, Zhi-Rui; Wang, Chen-Chen; Sun, Xiang-Jie; Yang, Zhao-Zhi; Chen, Xing-Xing; Shao, Zhi-Ming; Yu, Xiao-Li; Guo, Xiao-Mao

    2018-04-01

    The aim of this study was to explore the independent prognostic factors related to postoperative recurrence-free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. According to histological type, patients with benign PTBs were classified as a low-risk group, while borderline and malignant PTBs were classified as a high-risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups, and a nomogram was generated to predict recurrence-free survival at 1, 3, and 5 years. Among the 404 patients, 168 (41.6%) patients had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty-five patients experienced postoperative local recurrence, including six benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low-risk group, while the surgical approach and tumor border were independent prognostic factors for RFS in the high-risk group, and patients receiving simple excision with an infiltrative tumor border had a higher recurrence rate. A nomogram developed based on clinicopathologic features and surgical approaches could predict recurrence-free survival at 1, 3, and 5 years. For high-risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, degree of stromal cell hyperplasia, and atypia can be applied for patient counseling and clinical management. The efficacy of adjuvant radiotherapy remains uncertain. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. Tumor vascular-targeted co-delivery of anti-angiogenesis and chemotherapeutic agents by mesoporous silica nanoparticle-based drug delivery system for synergetic therapy of tumor

    Directory of Open Access Journals (Sweden)

    Li X

    2015-12-01

    Full Text Available Xiaoyu Li, Meiying Wu, Limin Pan, Jianlin Shi State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: To overcome the drawback of drug non-selectivity in traditional chemotherapy, the construction of multifunctional targeting drug delivery systems is one of the most effective and prevailing approaches. The intratumoral anti-angiogenesis and the tumor cell-killing are two basic approaches in fighting tumors. Herein we report a novel tumor vascular-targeting multidrug delivery system using mesoporous silica nanoparticles as carrier to co-load an antiangiogenic agent (combretastatin A4 and a chemotherapeutic drug (doxorubicin and conjugate with targeting molecules (iRGD peptide for combined anti-angiogenesis and chemotherapy. Such a dual-loaded drug delivery system is capable of delivering the two agents at tumor vasculature and then within tumors through a differentiated drug release strategy, which consequently results in greatly improved antitumor efficacy at a very low doxorubicin dose of 1.5 mg/kg. The fast release of the antiangiogenic agent at tumor vasculatures led to the disruption of vascular structure and had a synergetic effect with the chemotherapeutic drug slowly released in the following delivery of chemotherapeutic drug into tumors. Keywords: mesoporous silica nanoparticles, drug delivery, tumor vasculatures targeting, antiangiogenic agent

  18. Clinical efficacy and safety of surface imaging guided radiosurgery (SIG-RS) in the treatment of benign skull base tumors.

    Science.gov (United States)

    Lau, Steven K M; Patel, Kunal; Kim, Teddy; Knipprath, Erik; Kim, Gwe-Ya; Cerviño, Laura I; Lawson, Joshua D; Murphy, Kevin T; Sanghvi, Parag; Carter, Bob S; Chen, Clark C

    2017-04-01

    Frameless, surface imaging guided radiosurgery (SIG-RS) is a novel platform for stereotactic radiosurgery (SRS) wherein patient positioning is monitored in real-time through infra-red camera tracking of facial topography. Here we describe our initial clinical experience with SIG-RS for the treatment of benign neoplasms of the skull base. We identified 48 patients with benign skull base tumors consecutively treated with SIG-RS at a single institution between 2009 and 2011. Patients were diagnosed with meningioma (n = 22), vestibular schwannoma (n = 20), or nonfunctional pituitary adenoma (n = 6). Local control and treatment-related toxicity were retrospectively assessed. Median follow-up was 65 months (range 61-72 months). Prescription doses were 12-13 Gy in a single fraction (n = 18), 8 Gy × 3 fractions (n = 6), and 5 Gy × 5 fractions (n = 24). Actuarial tumor control rate at 5 years was 98%. No grade ≥3 treatment-related toxicity was observed. Grade ≤2 toxicity was associated with symptomatic lesions (p = 0.049) and single fraction treatment (p = 0.005). SIG-RS for benign skull base tumors produces clinical outcomes comparable to conventional frame-based SRS techniques while enhancing patient comfort.

  19. Molecular mechanisms for synergistic effect of proteasome inhibitors with platinum-based therapy in solid tumors.

    Science.gov (United States)

    Chao, Angel; Wang, Tzu-Hao

    2016-02-01

    The successful development of the proteasome inhibitor bortezomib as an anticancer drug has improved survival in patients with multiple myeloma. With the emergence of the newly US Food and Drug Administration-approved proteasome inhibitor carfilzomib, ongoing trials are investigating this compound and other proteasome inhibitors either alone or in combination with other chemotherapy drugs. However, in solid tumors, the efficacy of proteasome inhibitors has not lived up to expectations. Results regarding the potential clinical efficacy of bortezomib combined with other agents in the treatment of solid tumors are eagerly awaited. Recent identification of the molecular mechanisms (involving apoptosis and autophagy) by which bortezomib and cisplatin can overcome chemotherapy resistance and sensitize tumor cells to anticancer therapy can provide insights into the development of novel therapeutic strategies for patients with solid malignancies. Copyright © 2016. Published by Elsevier B.V.

  20. Feasibility of using single photon counting X-ray for lung tumor position estimation based on 4D-CT

    Energy Technology Data Exchange (ETDEWEB)

    Aschenbrenner, Katharina P.; Hesser, Juergen W. [Heidelberg Univ., Mannheim (Germany). Dept. of Experimental Radiation Oncology; Heidelberg Univ. (Germany). IWR; Guthier, Christian V. [Heidelberg Univ., Mannheim (Germany). Dept. of Experimental Radiation Oncology; Lyatskaya, Yulia [Brigham and Women' s Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Boda-Heggemann, Judit; Wenz, Frederik [Heidelberg Univ., Mannheim (Germany). Dept. of Radiation Oncology

    2017-10-01

    In stereotactic body radiation therapy of lung tumors, reliable position estimation of the tumor is necessary in order to minimize normal tissue complication rate. While kV X-ray imaging is frequently used, continuous application during radiotherapy sessions is often not possible due to concerns about the additional dose. Thus, ultra low-dose (ULD) kV X-ray imaging based on a single photon counting detector is suggested. This paper addresses the lower limit of photons to locate the tumor reliably with an accuracy in the range of state-of-the-art methods, i.e. a few millimeters. 18 patient cases with four dimensional CT (4D-CT), which serves as a-priori information, are included in the study. ULD cone beam projections are simulated from the 4D-CTs including Poisson noise. The projections from the breathing phases which correspond to different tumor positions are compared to the ULD projection by means of Poisson log-likelihood (PML) and correlation coefficient (CC), and template matching under these metrics. The results indicate that in full thorax imaging five photons per pixel suffice for a standard deviation in tumor positions of less than half a breathing phase. Around 50 photons per pixel are needed to achieve this accuracy with the field of view restricted to the tumor region. Compared to CC, PML tends to perform better for low photon counts and shifts in patient setup. Template matching only improves the position estimation in high photon counts. The quality of the reconstruction is independent of the projection angle. The accuracy of the proposed ULD single photon counting system is in the range of a few millimeters and therefore comparable to state-of-the-art tumor tracking methods. At the same time, a reduction in photons per pixel by three to four orders of magnitude relative to commercial systems with flatpanel detectors can be achieved. This enables continuous kV image-based position estimation during all fractions since the additional dose to the

  1. En Bloc Resection of Primary Malignant Bone Tumor in the Cervical Spine Based on 3-Dimensional Printing Technology.

    Science.gov (United States)

    Xiao, Jian-Ru; Huang, Wen-Ding; Yang, Xing-Hai; Yan, Wang-Jun; Song, Dian-Wen; Wei, Hai-Feng; Liu, Tie-Long; Wu, Zhi-Peng; Yang, Cheng

    2016-05-01

    To investigate the feasibility and safety of en bloc resection of cervical primary malignant bone tumors by a combined anterior and posterior approach based on a three-dimensional (3-D) printing model. Five patients with primary malignant bone tumors of the cervical spine underwent en bloc resection via a one-stage combined anteroposterior approach in our hospital from March 2013 to June 2014. They comprised three men and two women of mean age 47.2 years (range, 26-67 years). Three of the tumors were chondrosarcomas and two chordomas. Preoperative 3-D printing models were created by 3-D printing technology. Sagittal en bloc resections were planned based on these models and successfully performed. A 360° reconstruction was performed by spinal instrumentation in all cases. Surgical margins, perioperative complications, local control rate and survival rate were assessed. All patients underwent en bloc excision via a combined posterior and anterior approach in one stage. Mean operative time and estimated blood loss were 465 minutes and 1290 mL, respectively. Mean follow-up was 21 months. Wide surgical margins were achieved in two patients and marginal resection in three; these three patients underwent postoperative adjuvant radiation therapy. One vertebral artery was ligated and sacrificed in each of three patients. Nerve root involved by tumor was sacrificed in three patients with preoperative upper extremity weakness. One patient (Case 3) had significant transient radiculopathy with paresis postoperatively. Another (Case 4) with C 4 and C 5 chordoma had respiratory difficulties and pneumonia after surgery postoperatively. He recovered completely after 2 weeks' management with a tracheotomy tube and antibiotics in the intensive care unit. No cerebrovascular complications and wound infection were observed. No local recurrence or instrumentation failure were detected during follow-up. Though technically challenging, it is feasible and safe to perform en

  2. Feasibility of using single photon counting X-ray for lung tumor position estimation based on 4D-CT.

    Science.gov (United States)

    Aschenbrenner, Katharina P; Guthier, Christian V; Lyatskaya, Yulia; Boda-Heggemann, Judit; Wenz, Frederik; Hesser, Jürgen W

    2017-09-01

    In stereotactic body radiation therapy of lung tumors, reliable position estimation of the tumor is necessary in order to minimize normal tissue complication rate. While kV X-ray imaging is frequently used, continuous application during radiotherapy sessions is often not possible due to concerns about the additional dose. Thus, ultra low-dose (ULD) kV X-ray imaging based on a single photon counting detector is suggested. This paper addresses the lower limit of photons to locate the tumor reliably with an accuracy in the range of state-of-the-art methods, i.e. a few millimeters. 18 patient cases with four dimensional CT (4D-CT), which serves as a-priori information, are included in the study. ULD cone beam projections are simulated from the 4D-CTs including Poisson noise. The projections from the breathing phases which correspond to different tumor positions are compared to the ULD projection by means of Poisson log-likelihood (PML) and correlation coefficient (CC), and template matching under these metrics. The results indicate that in full thorax imaging five photons per pixel suffice for a standard deviation in tumor positions of less than half a breathing phase. Around 50 photons per pixel are needed to achieve this accuracy with the field of view restricted to the tumor region. Compared to CC, PML tends to perform better for low photon counts and shifts in patient setup. Template matching only improves the position estimation in high photon counts. The quality of the reconstruction is independent of the projection angle. The accuracy of the proposed ULD single photon counting system is in the range of a few millimeters and therefore comparable to state-of-the-art tumor tracking methods. At the same time, a reduction in photons per pixel by three to four orders of magnitude relative to commercial systems with flatpanel detectors can be achieved. This enables continuous kV image-based position estimation during all fractions since the additional dose to the

  3. Feasibility of using single photon counting X-ray for lung tumor position estimation based on 4D-CT

    International Nuclear Information System (INIS)

    Aschenbrenner, Katharina P.; Hesser, Juergen W.; Boda-Heggemann, Judit; Wenz, Frederik

    2017-01-01

    In stereotactic body radiation therapy of lung tumors, reliable position estimation of the tumor is necessary in order to minimize normal tissue complication rate. While kV X-ray imaging is frequently used, continuous application during radiotherapy sessions is often not possible due to concerns about the additional dose. Thus, ultra low-dose (ULD) kV X-ray imaging based on a single photon counting detector is suggested. This paper addresses the lower limit of photons to locate the tumor reliably with an accuracy in the range of state-of-the-art methods, i.e. a few millimeters. 18 patient cases with four dimensional CT (4D-CT), which serves as a-priori information, are included in the study. ULD cone beam projections are simulated from the 4D-CTs including Poisson noise. The projections from the breathing phases which correspond to different tumor positions are compared to the ULD projection by means of Poisson log-likelihood (PML) and correlation coefficient (CC), and template matching under these metrics. The results indicate that in full thorax imaging five photons per pixel suffice for a standard deviation in tumor positions of less than half a breathing phase. Around 50 photons per pixel are needed to achieve this accuracy with the field of view restricted to the tumor region. Compared to CC, PML tends to perform better for low photon counts and shifts in patient setup. Template matching only improves the position estimation in high photon counts. The quality of the reconstruction is independent of the projection angle. The accuracy of the proposed ULD single photon counting system is in the range of a few millimeters and therefore comparable to state-of-the-art tumor tracking methods. At the same time, a reduction in photons per pixel by three to four orders of magnitude relative to commercial systems with flatpanel detectors can be achieved. This enables continuous kV image-based position estimation during all fractions since the additional dose to the

  4. Dendritic-cell-based immunotherapy evokes potent anti-tumor immune responses in CD105+ human renal cancer stem cells.

    Science.gov (United States)

    Zhang, Xiao-Fei; Weng, De-Sheng; Pan, Ke; Zhou, Zi-Qi; Pan, Qiu-Zhong; Zhao, Jing-Jing; Tang, Yan; Jiang, Shan-Shan; Chen, Chang-Long; Li, Yong-Qiang; Zhang, Hong-Xia; Chang, Alfred E; Wicha, Max S; Zeng, Yi-Xin; Li, Qiao; Xia, Jian-Chuan

    2017-11-01

    Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and resistance to therapeutic agents; they are usually less sensitive to conventional cancer therapies, and could cause tumor relapse. An ideal therapeutic strategy would therefore be to selectively target and destroy CSCs, thereby preventing tumor relapse. The aim of the present study was to evaluate the effectiveness of dendritic cells (DCs) pulsed with antigen derived from CD105+ human renal cell carcinoma (RCC) CSCs against renal cancer cells in vitro and in vivo. We identified "stem-like" characteristics of CD105+ cells in two human RCC cell lines: A498 and SK-RC-39. Loading with cell lysates did not change the characteristics of the DCs. However, DCs loaded with lysates derived from CD105+ CSCs induced more functionally specific active T cells and specific antibodies against CSCs, and clearly depressed the tumor growth in mice. Our results could form the basis for a novel strategy to improve the efficacy of DC-based immunotherapy for human RCC. © 2017 Wiley Periodicals, Inc.

  5. Primary tumor resection in metastatic breast cancer: A propensity-matched analysis, 1988-2011 SEER data base.

    Science.gov (United States)

    Vohra, Nasreen A; Brinkley, Jason; Kachare, Swapnil; Muzaffar, Mahvish

    2018-03-02

    Primary tumor resection (PTR) in metastatic breast cancer is not a standard treatment modality, and its impact on survival is conflicting. The primary objective of this study was to analyze impact of PTR on survival in metastatic patients with breast cancer. A retrospective study of metastatic patients with breast cancer was conducted using the 1988-2011 Surveillance, Epidemiology, and End Results (SEER) data base. Cox proportional hazards regression models were used to evaluate the relationship between PTR and survival and to adjust for the heterogeneity between the groups, and a propensity score-matched analysis was also performed. A total of 29 916 patients with metastatic breast cancer were included in the study, and 15 129 (51%) of patients underwent primary tumor resection, and 14 787 (49%) patients did not undergo surgery. Overall, decreasing trend in PTR for metastatic breast cancer in last decades was noted. Primary tumor resection was associated with a longer median OS (34 vs 18 months). In a propensity score-matched analysis, prognosis was also more favorable in the resected group (P = .0017). Primary tumor resection in metastatic breast cancer was associated with survival improvement, and the improvement persisted in propensity-matched analysis. © 2018 Wiley Periodicals, Inc.

  6. Effect of Chemical Prevention Drugs-based MicroRNAs and Their Target Genes 
on Tumor Inhibition

    Directory of Open Access Journals (Sweden)

    Yanhui JIANG

    2015-04-01

    Full Text Available Chemopreventive drugs including natural chemopreventive drugs and synthetic chemopreventive drugs, it not only can prevent cancer, can also play a role in tumor treatment. MicroRNAs (miRNAs is a kind of short chains of non-coding RNA, regulating the expression of many genes through the way of degradation of mRNA or inhibitting mRNA translation. In recent years, more and more studies have shown that chemopreventive drugs through influence the expression of miRNAs and their target genes play a role in the prevention and treatment in a variety of tumors, and chemopreventive drugs on the experimental study of miRNAs and their target genes in tumor have demonstrated a good safety and efficacy. Effect on chemopreventive drugs-based microRNAs and their target genes into cancer cells will be expected as a new starting point for cancer research. The thesis expounds and analyzes between the natural chemopreventive drugs and synthetic chemopreventive drugs and miRNAs and their target genes in tumor research progress.

  7. Development of nano radiopharmaceutical based on Bevacizumab labelled with Technetium-99m for early diagnosis of gastrointestinal stromal tumor; Desenvolvimento de nanorradiofarmaco a base de Bevacizumabe marcado com tecnecio-99m para diagnostico precoce do tumor estromal gastrointestinal

    Energy Technology Data Exchange (ETDEWEB)

    Braga, Thais Ligiero

    2015-06-01

    The development of new radiopharmaceuticals is an essential activity to improve nuclear medicine, and essential for the early and effective diagnosis of oncological diseases. Among the various possibilities current research in the world, the radiopharmaceuticals to chemotherapeutic base may be the most effective in detecting tumors, particularly Gastrointestinal Stromal Tumor (GIST), the Metastatic Renal Cell Carcinoma and neuroendocrine pancreatic tumors. However, difficulties in directing, as well as adhesion of the radiopharmaceutical in the desired location, are currently the main problems in the early detection and treatment of some of these tumors. Advances in the field of nanotechnology, particularly in recent years, indicate significant contribution to overcoming these obstacles, particularly in the implementation of molecular barriers as well as the functionalization of the nanoparticles, thereby improving targeting by the use of surface nucleotides, and the increased adhesion, which facilitates the release of the drug and therefore increases the chances of early diagnosis and more effective treatment. This study aimed to the production, characterization and evaluation of cytotoxicity, as well as in vivo biodistribution test Bevacizumab nanoparticles labeled with Technetium-99m radionuclide for detection of type GIST tumors. Bevacizumab was encapsulated in the form of nanoparticles by the emulsification method using double poly-acetic acid and polyvinyl alcohol polymers (PLA / PVA) at a concentration of 2% of the monoclonal antibody. The characterization of the nanoparticles was performed by the technique of scanning electron microscopy (SEM). The cytotoxicity assessment was performed by XTT assay with various cell lines of solid tumor cells. The labeling with technetium-99m was done by the direct method, and its yield determined by paper chromatography using paper Whatmam 1 as the stationary phase and acetone as mobile phase. In the biodistribution study

  8. MRI-based tumor motion characterization and gating schemes for radiation therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Heerkens, Hanne D.; Vulpen, Marco van; Berg, Cornelis A.T. van den; Tijssen, Rob H.N.; Crijns, Sjoerd P.M.; Molenaar, Izaak Q.; Santvoort, Hjalmar C. van; Reerink, Onne; Meijer, Gert J.

    2014-01-01

    Background and purpose: To characterize pancreatic tumor motion and to develop a gating scheme for radiotherapy in pancreatic cancer. Materials and methods: Two cine MRIs of 60 s each were performed in fifteen pancreatic cancer patients, one in sagittal direction and one in coronal direction. A Minimum Output Sum of Squared Error (MOSSE) adaptive correlation filter was used to quantify tumor motion in craniocaudal, lateral and anteroposterior directions. To develop a gating scheme, stability of the breathing phases was examined and a gating window assessment was created, incorporating tumor motion, treatment time and motion margins. Results: The largest tumor motion was found in craniocaudal direction, with an average peak-to-peak amplitude of 15 mm (range 6–34 mm). Amplitude of the tumor in the anteroposterior direction was on average 5 mm (range 1–13 mm). The least motion was seen in lateral direction (average 3 mm, range 2–5 mm). The end exhale position was the most stable position in the breathing cycle and tumors spent more time closer to the end exhale position than to the end inhale position. On average, a margin of 25% of the maximum craniocaudal breathing amplitude was needed to achieve full target coverage with a duty cycle of 50%. When reducing the duty cycle to 50%, a margin of 5 mm was sufficient to cover the target in 11 out of 15 patients. Conclusion: Gated delivery for radiotherapy of pancreatic cancer is best performed around the end exhale position as this is the most stable position in the breathing cycle. Considerable margin reduction can be established at moderate duty cycles, yielding acceptable treatment efficiency. However, motion patterns and amplitude do substantially differ between individual patients. Therefore, individual treatment strategies should be considered for radiotherapy in pancreatic cancer

  9. Gamma knife radiosurgery for glomus jugulare tumors: therapeutic advantages of minimalism in the skull base.

    Science.gov (United States)

    Sharma, Manish S; Gupta, A; Kale, S S; Agrawal, D; Mahapatra, A K; Sharma, B S

    2008-01-01

    Glomus jugulare (GJ) tumors are paragangliomas found in the region of the jugular foramen. Surgery with/without embolization and conventional radiotherapy has been the traditional management option. To analyze the efficacy of gamma knife radiosurgery (GKS) as a primary or an adjunctive form of therapy. A retrospective analysis of patients who received GKS at a tertiary neurosurgical center was performed. Of the 1601 patients who underwent GKS from 1997 to 2006, 24 patients with GJ underwent 25 procedures. The average age of the cohort was 46.6 years (range, 22-76 years) and the male to female ratio was 1:2. The most common neurological deficit was IX, X, XI cranial nerve paresis (15/24). Fifteen patients received primary GKS. Mean tumor size was 8.7 cc (range 1.1-17.2 cc). The coverage achieved was 93.1% (range 90-97%) using a mean tumor margin dose of 16.4 Gy (range 12-25 Gy) at a mean isodose of 49.5% (range 45-50%). Thirteen patients (six primary and seven secondary) were available for follow-up at a median interval of 24 months (range seven to 48 months). The average tumor size was 7.9 cc (range 1.1-17.2 cc). Using a mean tumor margin dose of 16.3 Gy (range 12-20 Gy) 93.6% coverage (range 91-97%) was achieved. Six patients improved clinically. A single patient developed transient trigeminal neuralgia. Magnetic resonance imaging follow-up was available for 10 patients; seven recorded a decrease in size. There was no tumor progression. Gamma knife radiosurgery is a safe and effective primary and secondary modality of treatment for GJ.

  10. Developing noise control strategies for entire railway networks

    Science.gov (United States)

    Oertli, Jakob

    2006-06-01

    The EU Environmental Noise Directive (2002/49) requires member states to deliver noise maps to the commission by 2007 and action plans by 2008 both for agglomerations as well as for major roads, railways and airports. Noise mitigation projects resulting from action plans are usually very expensive and therefore may threaten the economic viability of the railways in the current harsh competitive transport market, thus hindering sustainable transport policies. It is therefore of vital interest that the action plans and the resulting projects are designed in the most cost-effective way possible. The EU and Union of Railways (UIC) sponsored project Strategies and Tools to Assess and Implement noise Reducing measures for Railway Systems (STAIRRS) recognized this need and developed a tool, with which such optimal solutions can be obtained for entire railway networks. Since data collection is the most expensive part of the analysis, noise mapping data is ideally collected in such a way that it can be used for the calculation of the different scenarios, from which the most cost-effective action plans are chosen. The paper shows how the STAIRRS tool is used for this purpose and how cost-effectiveness considerations have led to optimal railway noise mitigation strategies in Switzerland and have given a basis for noise related decision making in Luxembourg.

  11. Use of the entire spectrum of irradiated alanine for dosimetry

    International Nuclear Information System (INIS)

    Dolo, J.M.; Moignau, F.

    2005-01-01

    Alanine is an amino acid commonly used in ESR dosimetry as a reference detector. The classic approach for the measurement of irradiated samples is to determine the amplitude of the central peak of the first derivative spectrum. It is generally considered that this technique represents the best and most reproducible solution for achieving an accurate proportionality between the concentration of free radicals inside the resonant cavity, characterized by the amplitude, and the dose. It is also accepted that this central peak corresponds to the free radical CH 3 .CHCOO - . The hyperfine structure of this radical in the spectrum shows five main peaks with the approximate ratios 1:4:6:4:1 as regards coupling. This paper presents another approach featuring analysis of the entire spectrum: (i) ratios of identified peaks (ii) ratio variation vs time with regard to several parameters affecting fading. These variations in the alanine spectrum are probably correlated with the variation of the concentrations of different free radical species. These variations and their positions in the spectrum are very important constraints that increase the uncertainty of this type of measurement

  12. Comparison between two meshless methods based on collocation technique for the numerical solution of four-species tumor growth model

    Science.gov (United States)

    Dehghan, Mehdi; Mohammadi, Vahid

    2017-03-01

    As is said in [27], the tumor-growth model is the incorporation of nutrient within the mixture as opposed to being modeled with an auxiliary reaction-diffusion equation. The formulation involves systems of highly nonlinear partial differential equations of surface effects through diffuse-interface models [27]. Simulations of this practical model using numerical methods can be applied for evaluating it. The present paper investigates the solution of the tumor growth model with meshless techniques. Meshless methods are applied based on the collocation technique which employ multiquadrics (MQ) radial basis function (RBFs) and generalized moving least squares (GMLS) procedures. The main advantages of these choices come back to the natural behavior of meshless approaches. As well as, a method based on meshless approach can be applied easily for finding the solution of partial differential equations in high-dimension using any distributions of points on regular and irregular domains. The present paper involves a time-dependent system of partial differential equations that describes four-species tumor growth model. To overcome the time variable, two procedures will be used. One of them is a semi-implicit finite difference method based on Crank-Nicolson scheme and another one is based on explicit Runge-Kutta time integration. The first case gives a linear system of algebraic equations which will be solved at each time-step. The second case will be efficient but conditionally stable. The obtained numerical results are reported to confirm the ability of these techniques for solving the two and three-dimensional tumor-growth equations.

  13. Modeling protective anti-tumor immunity via preventative cancer vaccines using a hybrid agent-based and delay differential equation approach.

    Science.gov (United States)

    Kim, Peter S; Lee, Peter P

    2012-01-01

    A next generation approach to cancer envisions developing preventative vaccinations to stimulate a person's immune cells, particularly cytotoxic T lymphocytes (CTLs), to eliminate incipient tumors before clinical detection. The purpose of our study is to quantitatively assess whether such an approach would be feasible, and if so, how many anti-cancer CTLs would have to be primed against tumor antigen to provide significant protection. To understand the relevant dynamics, we develop a two-compartment model of tumor-immune interactions at the tumor site and the draining lymph node. We model interactions at the tumor site using an agent-based model (ABM) and dynamics in the lymph node using a system of delay differential equations (DDEs). We combine the models into a hybrid ABM-DDE system and investigate dynamics over a wide range of parameters, including cell proliferation rates, tumor antigenicity, CTL recruitment times, and initial memory CTL populations. Our results indicate that an anti-cancer memory CTL pool of 3% or less can successfully eradicate a tumor population over a wide range of model parameters, implying that a vaccination approach is feasible. In addition, sensitivity analysis of our model reveals conditions that will result in rapid tumor destruction, oscillation, and polynomial rather than exponential decline in the tumor population due to tumor geometry.

  14. Validation of a Web-Based Tool to Predict the Ipsilateral Breast Tumor Recurrence (IBTR! 2.0) after Breast-Conserving Therapy for Korean Patients.

    Science.gov (United States)

    Jung, Seung Pil; Hur, Sung Mo; Lee, Se Kyung; Kim, Sangmin; Choi, Min-Young; Bae, Soo Youn; Kim, Jiyoung; Kim, Min Kuk; Kil, Won Ho; Choe, Jun-Ho; Kim, Jung-Han; Kim, Jee Soo; Nam, Seok Jin; Bae, Jeoung Won; Lee, Jeong Eon

    2013-03-01

    IBTR! 2.0 is a web-based nomogram that predicts the 10-year ipsilateral breast tumor recurrence (IBTR) rate after breast-conserving therapy. We validated this nomogram in Korean patients. The nomogram was tested for 520 Korean patients, who underwent breast-conserving surgery followed by radiation therapy. Predicted and observed 10-year outcomes were compared for the entire cohort and for each group, predefined by nomogram-predicted risks: group 1, 10%. In overall patients, the overall 10 year predicted and observed estimates of IBTR were 5.22% and 5.70% (p=0.68). In group 1, (n=124), the predicted and observed estimates were 2.25% and 1.80% (p=0.73), in group 2 (n=177), 3.95% and 3.90% (p=0.97), in group 3 (n=181), 7.14% and 8.80% (p=0.42), and in group 4 (n=38), 11.66% and 14.90% (p=0.73), respectively. In a previous validation of this nomogram based on American patients, nomogram-predicted IBTR rates were overestimated in the high-risk subgroup. However, our results based on Korean patients showed that the observed IBTR was higher than the predicted estimates in groups 3 and 4. This difference may arise from ethnic differences, as well as from the methods used to detect IBTR and the healthcare environment. IBTR! 2.0 may be considered as an acceptable nomogram in Korean patients with low- to moderate-risk of in-breast recurrence. Before widespread use of this nomogram, the IBTR! 2.0 needs a larger validation study and continuous modification.

  15. A novel gene therapy-based approach that selectively targets hypoxic regions within solid tumors

    International Nuclear Information System (INIS)

    Dougherty, S.T.; Dougherty, G.J.; Davis, P.D.

    2003-01-01

    There is compelling evidence that malignant cells present within the hypoxic regions that are commonly found within solid tumors contribute significantly to local recurrence following radiation therapy. We describe now a novel strategy designed to target such cells that exploits the differential production within hypoxic regions of the pro-angiogenic cytokine vascular endothelial cell growth factor (VEGF). Specifically, we have generated cDNA constructs that encode two distinct chimeric cell surface proteins that incorporate, respectively, the extracellular domains of the VEGF receptors Flk-1 or Flt-1, fused in frame to the membrane spanning and cytoplasmic domains of the pro-apoptotic protein Fas. Both chimeric proteins (Flk/Fas and Flt/Fas) appear stable and can be readily detected on the surface of transfected cells by Western blot and/or FACS analysis. Importantly, tumor cells expressing the chimeric proteins were rapidly killed in a dose-dependent fashion upon the addition of exogenous recombinant VEGF. Adenoviral vectors encoding Flk/Fas have been generated and shown to induce tumor cells to undergo apoptosis upon transfer to hypoxic conditions in vitro. This activity is dependent upon the endogenous production of VEGF. Studies are currently underway to test the ability of adenoviral Flk/Fas (Ad.Flk/Fas) to reduce tumor recurrence in vivo when used as an adjuvant therapy in conjunction with clinically relevant doses of ionizing radiation

  16. Modeling tumor control probability for spatially inhomogeneous risk of failure based on clinical outcome data

    DEFF Research Database (Denmark)

    Lühr, Armin; Löck, Steffen; Jakobi, Annika

    2017-01-01

    PURPOSE: Objectives of this work are (1) to derive a general clinically relevant approach to model tumor control probability (TCP) for spatially variable risk of failure and (2) to demonstrate its applicability by estimating TCP for patients planned for photon and proton irradiation. METHODS AND ...

  17. Effective experimental tumor therapy with targeted polymer drug delivery systems based on HPMA copolymers.

    Czech Academy of Sciences Publication Activity Database

    Šírová, Milada; Horková, Veronika; Sivák, Ladislav; Etrych, Tomáš; Říhová, Blanka; Studenovský, Martin

    SI (2016), s. 24-24 ISSN 0014-2980. [3rd Meeting of Middle – European Societies for Immunology and Allergology. 01.12.2016-03.12.2016, Budapest ] R&D Projects: GA ČR(CZ) GA14-12742S Institutional support: RVO:61388971 ; RVO:61389013 Keywords : Tumor therapy * polymer drug * HPMA copolymers Subject RIV: EE - Microbiology, Virology

  18. [Computer aided diagnosis model for lung tumor based on ensemble convolutional neural network].

    Science.gov (United States)

    Wang, Yuanyuan; Zhou, Tao; Lu, Huiling; Wu, Cuiying; Yang, Pengfei

    2017-08-01

    The convolutional neural network (CNN) could be used on computer-aided diagnosis of lung tumor with positron emission tomography (PET)/computed tomography (CT), which can provide accurate quantitative analysis to compensate for visual inertia and defects in gray-scale sensitivity, and help doctors diagnose accurately. Firstly, parameter migration method is used to build three CNNs (CT-CNN, PET-CNN, and PET/CT-CNN) for lung tumor recognition in CT, PET, and PET/CT image, respectively. Then, we aimed at CT-CNN to obtain the appropriate model parameters for CNN training through analysis the influence of model parameters such as epochs, batchsize and image scale on recognition rate and training time. Finally, three single CNNs are used to construct ensemble CNN, and then lung tumor PET/CT recognition was completed through relative majority vote method and the performance between ensemble CNN and single CNN was compared. The experiment results show that the ensemble CNN is better than single CNN on computer-aided diagnosis of lung tumor.

  19. Predicting Response to Chemotherapy based on Tumor Marker Trend in Patients with Testicular Cancer

    Czech Academy of Sciences Publication Activity Database

    Nekulová, M.; Pecen, Ladislav; Kocák, I.; Šimíčková, M.; Frgala, T.; Pilný, R.; Valík, D.

    2004-01-01

    Roč. 8, - (2004), s. 70 ISSN 1211-8869. [CECHTUMA 2004. 01.10.2004-03.10.2004, Prague] Institutional research plan: CEZ:AV0Z1030915 Keywords : evaluation of therapy response * model of tumor markers decrease * testicular cancer Subject RIV: BB - Applied Statistics, Operational Research

  20. RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics.

    Science.gov (United States)

    Best, Myron G; Sol, Nik; Kooi, Irsan; Tannous, Jihane; Westerman, Bart A; Rustenburg, François; Schellen, Pepijn; Verschueren, Heleen; Post, Edward; Koster, Jan; Ylstra, Bauke; Ameziane, Najim; Dorsman, Josephine; Smit, Egbert F; Verheul, Henk M; Noske, David P; Reijneveld, Jaap C; Nilsson, R Jonas A; Tannous, Bakhos A; Wesseling, Pieter; Wurdinger, Thomas

    2015-11-09

    Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies". Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Low values of 5-hydroxymethylcytosine (5hmC), the "sixth base," are associated with anaplasia in human brain tumors.

    Science.gov (United States)

    Kraus, Theo F J; Globisch, Daniel; Wagner, Mirko; Eigenbrod, Sabina; Widmann, David; Münzel, Martin; Müller, Markus; Pfaffeneder, Toni; Hackner, Benjamin; Feiden, Wolfgang; Schüller, Ulrich; Carell, Thomas; Kretzschmar, Hans A

    2012-10-01

    5-Methylcytosine (5 mC) in genomic DNA has important epigenetic functions in embryonic development and tumor biology. 5-Hydroxymethylcytosine (5 hmC) is generated from 5 mC by the action of the TET (Ten-Eleven-Translocation) enzymes and may be an intermediate to further oxidation and finally demethylation of 5 mC. We have used immunohistochemistry (IHC) and isotope-based liquid chromatography mass spectrometry (LC-MS) to investigate the presence and distribution of 5 hmC in human brain and brain tumors. In the normal adult brain, IHC identified 61.5% 5 hmC positive cells in the cortex and 32.4% 5 hmC in white matter (WM) areas. In tumors, positive staining of cells ranged from 1.1% in glioblastomas (GBMs) (WHO Grade IV) to 8.9% in Grade I gliomas (pilocytic astrocytomas). In the normal adult human brain, LC-MS also showed highest values in cortical areas (1.17% 5 hmC/dG [deoxyguanosine]), in the cerebral WM we measured around 0.70% 5 hmC/dG. levels were related to tumor differentiation, ranging from lowest values of 0.078% 5 hmC/dG in GBMs (WHO Grade IV) to 0.24% 5 hmC/dG in WHO Grade II diffuse astrocytomas. 5 hmC measurements were unrelated to 5 mC values. We find that the number of 5 hmC positive cells and the amount of 5 hmC/dG in the genome that has been proposed to be related to pluripotency and lineage commitment in embryonic stem cells is also associated with brain tumor differentiation and anaplasia. Copyright © 2012 UICC.

  2. Experimental study of radiopharmaceuticals based on technetium-99m labeled derivative of glucose for tumor diagnosis

    Science.gov (United States)

    Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Bragina, O.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.; Dergilev, A.

    2016-06-01

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 minutes at room temperature. After centrifugation of the vials with cells, the supernatant was removed. Radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B 1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 minutes. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D- glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3±0.15MBq and 1.07±0.6MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio- D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  3. Development of nano radiopharmaceutical based on Bevacizumab labelled with Technetium-99m for early diagnosis of gastrointestinal stromal tumor

    International Nuclear Information System (INIS)

    Braga, Thais Ligiero

    2015-01-01

    The development of new radiopharmaceuticals is an essential activity to improve nuclear medicine, and essential for the early and effective diagnosis of oncological diseases. Among the various possibilities current research in the world, the radiopharmaceuticals to chemotherapeutic base may be the most effective in detecting tumors, particularly Gastrointestinal Stromal Tumor (GIST), the Metastatic Renal Cell Carcinoma and neuroendocrine pancreatic tumors. However, difficulties in directing, as well as adhesion of the radiopharmaceutical in the desired location, are currently the main problems in the early detection and treatment of some of these tumors. Advances in the field of nanotechnology, particularly in recent years, indicate significant contribution to overcoming these obstacles, particularly in the implementation of molecular barriers as well as the functionalization of the nanoparticles, thereby improving targeting by the use of surface nucleotides, and the increased adhesion, which facilitates the release of the drug and therefore increases the chances of early diagnosis and more effective treatment. This study aimed to the production, characterization and evaluation of cytotoxicity, as well as in vivo biodistribution test Bevacizumab nanoparticles labeled with Technetium-99m radionuclide for detection of type GIST tumors. Bevacizumab was encapsulated in the form of nanoparticles by the emulsification method using double poly-acetic acid and polyvinyl alcohol polymers (PLA / PVA) at a concentration of 2% of the monoclonal antibody. The characterization of the nanoparticles was performed by the technique of scanning electron microscopy (SEM). The cytotoxicity assessment was performed by XTT assay with various cell lines of solid tumor cells. The labeling with technetium-99m was done by the direct method, and its yield determined by paper chromatography using paper Whatmam 1 as the stationary phase and acetone as mobile phase. In the biodistribution study

  4. Generation of autologous tumor-specific T cells for adoptive transfer based on vaccination, in vitro restimulation and CD3/CD28 dynabead-induced T cell expansion

    DEFF Research Database (Denmark)

    Brimnes, Marie Klinge; Gang, Anne Ortved; Donia, Marco

    2012-01-01

    Adoptive cell transfer (ACT) of in vitro expanded autologous tumor-infiltrating lymphocytes (TIL) has been shown to exert therapeutic efficacy in melanoma patients. We aimed to develop an ACT protocol based on tumor-specific T cells isolated from peripheral blood and in vitro expanded by Dynabeads...

  5. Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Linda X.; Garg, Madhur; Lasala, Patrick; Kim, Mimi; Mah, Dennis; Chen, Chin-Cheng; Yaparpalvi, Ravindra; Mynampati, Dinesh; Kuo, Hsiang-Chi; Guha, Chandan; Kalnicki, Shalom [Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Neurosurgery, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Epidemiology and Population Health, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States)

    2011-03-15

    Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems, Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group

  6. A rationally designed combined treatment with an alphavirus-based cancer vaccine, sunitinib and low-dose tumor irradiation completely blocks tumor development

    NARCIS (Netherlands)

    Draghiciu, Oana; Boerma, Annemarie; Hoogeboom, Baukje Nynke; Nijman, Hans W.; Daemen, Toos

    2015-01-01

    The clinical efficacy of therapeutic cancer vaccines remains limited. For effective immunotherapeutic responses in cancer patients, multimodal approaches capable of both inducing antitumor immune responses and bypassing tumor-mediated immune escape seem essential. Here, we report on a combination

  7. The use of entire agreement clauses in contracts governed by Danish law

    DEFF Research Database (Denmark)

    Mitkidis, Katerina

    2017-01-01

    The article analyses the use of entire agreement (EA) clauses in contracts governed by Danish law. It (i) reviews the practice, based on interviews conducted with the representatives of Danish firms, judiciary and legal profession, (ii) analyses the implications of the practice under Danish...... contract law and related case law and (iii) offers recommendations on how EA clauses can be amended to minimise associated legal risks....

  8. Simultaneous quantitative detection of multiple tumor markers with a rapid and sensitive multicolor quantum dots based immunochromatographic test strip.

    Science.gov (United States)

    Wang, Chunying; Hou, Fei; Ma, Yicai

    2015-06-15

    A novel multicolor quantum dots (QDs) based immunochromatographic test strip (ICTS) was developed for simultaneous quantitative detection of multiple tumor markers, by utilizing alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA) as models. The immunosensor could realize simultaneous quantitative detection of tumor markers with only one test line and one control line on the nitrocellulose membrane (NC membrane) due to the introduction of multicolor QDs. In this method, a mixture of mouse anti-AFP McAb and mouse anti-CEA McAb was coated on NC membrane as test line and goat anti-mouse IgG antibody was coated as control line. Anti-AFP McAb-QDs546 conjugates and anti-CEA McAb-QDs620 conjugates were mixed and applied to the conjugate pad. Simultaneous quantitative detection of multiple tumor markers was achieved by detecting the fluorescence intensity of captured QDs labels on test line and control line using a test strip reader. Under the optimum conditions, AFP and CEA could be detected as low as 3 ng/mL and 2 ng/mL in 15 min with a sample volume of 80 μL, and no obvious cross-reactivity was observed. The immunosensor was validated with 130 clinical samples and in which it exhibited high sensitivity (93% for AFP and 87% for CEA) and specificity (94% for AFP and 97% for CEA). The immunosensor also demonstrated high recoveries (87.5-113% for AFP and 90-97.3% for CEA) and low relative standard deviations (RSDs) (2.8-6.2% for AFP and 4.9-9.6% for CEA) when testing spiked human serum. This novel multicolor QDs based ICTS provides an easy and rapid, simultaneous quantitative detecting strategy for point-of-care testing of tumor markers. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. A panoramic view of the skull base: systematic review of open and endoscopic endonasal approaches to four tumors.

    Science.gov (United States)

    Graffeo, Christopher S; Dietrich, August R; Grobelny, Bartosz; Zhang, Meng; Goldberg, Judith D; Golfinos, John G; Lebowitz, Richard; Kleinberg, David; Placantonakis, Dimitris G

    2014-08-01

    Endoscopic endonasal surgery has been established as the safest approach to pituitary tumors, yet its role in other common skull base lesions has not been established. To answer this question, we carried out a systematic review of reported series of open and endoscopic endonasal approaches to four major skull base tumors: olfactory groove meningiomas (OGM), tuberculum sellae meningiomas (TSM), craniopharyngiomas (CRA), and clival chordomas (CHO). Data from 162 studies containing 5,701 patients were combined and compared for differences in perioperative mortality, gross total resection (GTR), cerebrospinal fluid (CSF) leak, neurological morbidity, post-operative visual function, post-operative anosmia, post-operative diabetes insipidus (DI), and post-operative obesity/hyperphagia. Weighted average rates for each outcome were calculated using relative study size. Our findings indicate similar rates of GTR and perioperative mortality between open and endoscopic approaches for all tumor types. CSF leak was increased after endoscopic surgery. Visual function symptoms were more likely to improve after endoscopic surgery for TSM, CRA, and CHO. Post-operative DI and obesity/hyperphagia were significantly increased after open resection in CRA. Recurrence rates per 1,000 patient-years of follow-up were higher in endoscopy for OGM, TSM, and CHO. Trends for open and endoscopic surgery suggested modest improvement in all outcomes over time. Our observations suggest that endonasal endoscopy is a safe alternative to craniotomy and may be preferred for certain tumor types. However, endoscopic surgery is associated with higher rates of CSF leak, and possibly increased recurrence rates. Prospective study with long-term follow-up is required to verify these preliminary observations.

  10. A new anti-tumor strategy based on in vivo tumstatin overexpression after plasmid electrotransfer in muscle

    Energy Technology Data Exchange (ETDEWEB)

    Thevenard, Jessica, E-mail: jessica.thevenard@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); Ramont, Laurent, E-mail: lramont@chu-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); CHU de Reims, Avenue du Général Koenig, F-51092 Reims (France); Mir, Lluis M., E-mail: luis.mir@igr.fr [CNRS, UMR 8203, Institut Gustave Roussy, 114, Rue Edouard Vaillant, F-94805 Villejuif Cedex (France); Université Paris-Sud, UMR 8203, Institut Gustave Roussy, 114, Rue Edouard Vaillant, F-94405 Orsay Cedex (France); Dupont-Deshorgue, Aurélie, E-mail: aurelie.dupont@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); Maquart, François-Xavier, E-mail: fmaquart@chu-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); CHU de Reims, Avenue du Général Koenig, F-51092 Reims (France); Monboisse, Jean-Claude, E-mail: jc.monboisse@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); CHU de Reims, Avenue du Général Koenig, F-51092 Reims (France); Brassart-Pasco, Sylvie, E-mail: sylvie.brassart-pasco@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France)

    2013-03-22

    Highlights: ► A new therapeutic strategy based on tumstatin in vivo overexpression is proposed. ► pVAX1©–tumstatin electrotransfer in muscle mediates protein expression in muscle. ► A substantial expression of tumstatin is detected in the serum of electrotransfected mice. ► Tumstatin overexpression decreases tumor growth and increases mouse survival. -- Abstract: The NC1 domains from the different α(IV) collagen chains were found to exert anti-tumorigenic and/or anti-angiogenic activities. A limitation to the therapeutic use of these matrikines is the large amount of purified recombinant proteins, in the milligram range in mice that should be administered daily throughout the experimental procedures. In the current study, we developed a new therapeutic approach based on tumstatin (NC1α3(IV)) overexpression in vivo in a mouse melanoma model. Gene electrotransfer of naked plasmid DNA (pDNA) is particularly attractive because of its simplicity, its lack of immune responsiveness and its safety. The pDNA electrotransfer in muscle mediates a substantial gene expression that lasts several months. A pVAX1© vector containing the tumstatin cDNA was injected into the legs of C57BL/6 mice and submitted to electrotranfer. Sera were collected at different times and tumstatin was quantified by ELISA. Tumstatin secretion reached a plateau at day 21 with an expression level of 12 μg/mL. For testing the effects of tumstatin expression on tumor growth in vivo, B16F1 melanoma cells were subcutaneously injected in mice 7 days after empty pVAX1© (Mock) or pVAX1©–tumstatin electrotransfer. Tumstatin expression triggered a large decrease in tumor growth and an increase in mouse survival. This new therapeutic approach seems promising to inhibit tumor progression in vivo.

  11. Fabrication and evaluation of tumor-targeted positive MRI contrast agent based on ultrasmall MnO nanoparticles.

    Science.gov (United States)

    Huang, Haitao; Yue, Tao; Xu, Ke; Golzarian, Jafar; Yu, Jiahui; Huang, Jin

    2015-07-01

    Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd(3+) from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100nm and a longitudinal relaxivity (r1) of 10.2mM(-1)S(-1). Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T1-weighted MRI diagnosis of tumor. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  12. Tumor-Targeted Human T Cells Expressing CD28-Based Chimeric Antigen Receptors Circumvent CTLA-4 Inhibition.

    Directory of Open Access Journals (Sweden)

    Maud Condomines

    Full Text Available Adoptive T cell therapy represents a promising treatment for cancer. Human T cells engineered to express a chimeric antigen receptor (CAR recognize and kill tumor cells in a MHC-unrestricted manner and persist in vivo when the CAR includes a CD28 costimulatory domain. However, the intensity of the CAR-mediated CD28 activation signal and its regulation by the CTLA-4 checkpoint are unknown. We investigated whether T cells expressing an anti-CD19, CD3 zeta and CD28-based CAR (19-28z displayed the same proliferation and anti-tumor abilities than T cells expressing a CD3 zeta-based CAR (19z1 costimulated through the CD80/CD28, ligand/receptor pathway. Repeated in vitro antigen-specific stimulations indicated that 19-28z+ T cells secreted higher levels of Th1 cytokines and showed enhanced proliferation compared to those of 19z1+ or 19z1-CD80+ T cells. In an aggressive pre-B cell leukemia model, mice treated with 19-28z+ T cells had 10-fold reduced tumor progression compared to those treated with 19z1+ or 19z1-CD80+ T cells. shRNA-mediated CTLA-4 down-regulation in 19z1-CD80+ T cells significantly increased their in vivo expansion and anti-tumor properties, but had no effect in 19-28z+ T cells. Our results establish that CTLA-4 down-regulation may benefit human adoptive T cell therapy and demonstrate that CAR design can elude negative checkpoints to better sustain T cell function.

  13. A new anti-tumor strategy based on in vivo tumstatin overexpression after plasmid electrotransfer in muscle

    International Nuclear Information System (INIS)

    Thevenard, Jessica; Ramont, Laurent; Mir, Lluis M.; Dupont-Deshorgue, Aurélie; Maquart, François-Xavier; Monboisse, Jean-Claude; Brassart-Pasco, Sylvie

    2013-01-01

    Highlights: ► A new therapeutic strategy based on tumstatin in vivo overexpression is proposed. ► pVAX1©–tumstatin electrotransfer in muscle mediates protein expression in muscle. ► A substantial expression of tumstatin is detected in the serum of electrotransfected mice. ► Tumstatin overexpression decreases tumor growth and increases mouse survival. -- Abstract: The NC1 domains from the different α(IV) collagen chains were found to exert anti-tumorigenic and/or anti-angiogenic activities. A limitation to the therapeutic use of these matrikines is the large amount of purified recombinant proteins, in the milligram range in mice that should be administered daily throughout the experimental procedures. In the current study, we developed a new therapeutic approach based on tumstatin (NC1α3(IV)) overexpression in vivo in a mouse melanoma model. Gene electrotransfer of naked plasmid DNA (pDNA) is particularly attractive because of its simplicity, its lack of immune responsiveness and its safety. The pDNA electrotransfer in muscle mediates a substantial gene expression that lasts several months. A pVAX1© vector containing the tumstatin cDNA was injected into the legs of C57BL/6 mice and submitted to electrotranfer. Sera were collected at different times and tumstatin was quantified by ELISA. Tumstatin secretion reached a plateau at day 21 with an expression level of 12 μg/mL. For testing the effects of tumstatin expression on tumor growth in vivo, B16F1 melanoma cells were subcutaneously injected in mice 7 days after empty pVAX1© (Mock) or pVAX1©–tumstatin electrotransfer. Tumstatin expression triggered a large decrease in tumor growth and an increase in mouse survival. This new therapeutic approach seems promising to inhibit tumor progression in vivo

  14. Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery

    Science.gov (United States)

    Kesharwani, Prashant; Iyer, Arun K.

    2015-01-01

    Advances in the application of nanotechnology in medicine have given rise to multifunctional smart nanocarriers that can be engineered with tunable physicochemical characteristics to deliver one or more therapeutic agent(s) safely and selectively to cancer cells, including intracellular organelle-specific targeting. Dendrimers having properties resembling biomolecules, with well-defined 3D nanopolymeric architectures, are emerging as a highly attractive class of drug and gene delivery vector. The presence of numerous peripheral functional groups on hyperbranched dendrimers affords efficient conjugation of targeting ligands and biomarkers that can recognize and bind to receptors overexpressed on cancer cells for tumor-cell-specific delivery. The present review compiles the recent advances in dendrimer-mediated drug and gene delivery to tumors by passive and active targeting principles with illustrative examples. PMID:25555748

  15. Non-invasive focused ultrasound-based synergistic treatment of brain tumors

    Directory of Open Access Journals (Sweden)

    Ya-Jui Lin

    2016-09-01

    The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs, or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.

  16. Multimodality multiparametric imaging of early tumor response to a novel antiangiogenic therapy based on anticalins.

    Directory of Open Access Journals (Sweden)

    Reinhard Meier

    Full Text Available Anticalins are a novel class of targeted protein therapeutics. The PEGylated Anticalin Angiocal (PRS-050-PEG40 is directed against VEGF-A. The purpose of our study was to compare the performance of diffusion weighted imaging (DWI, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI and positron emission tomography with the tracer [18F]fluorodeoxyglucose (FDG-PET for monitoring early response to antiangiogenic therapy with PRS-050-PEG40. 31 mice were implanted subcutaneously with A673 rhabdomyosarcoma xenografts and underwent DWI, DCE-MRI and FDG-PET before and 2 days after i.p. injection of PRS-050-PEG40 (n = 13, Avastin (n = 6 or PBS (n = 12. Tumor size was measured manually with a caliper. Imaging results were correlated with histopathology. In the results, the tumor size was not significantly different in the treatment groups when compared to the control group on day 2 after therapy onset (P = 0.09. In contrast the imaging modalities DWI, DCE-MRI and FDG-PET showed significant differences between the therapeutic compared to the control group as early as 2 days after therapy onset (P<0.001. There was a strong correlation of the early changes in DWI, DCE-MRI and FDG-PET at day 2 after therapy onset and the change in tumor size at the end of therapy (r = -0.58, 0.71 and 0.67 respectively. The imaging results were confirmed by histopathology, showing early necrosis and necroptosis in the tumors. Thus multimodality multiparametric imaging was able to predict therapeutic success of PRS-050-PEG40 and Avastin as early as 2 days after onset of therapy and thus promising for monitoring early response of antiangiogenic therapy.

  17. A method for medulloblastoma tumor differentiation based on convolutional neural networks and transfer learning

    Science.gov (United States)

    Cruz-Roa, Angel; Arévalo, John; Judkins, Alexander; Madabhushi, Anant; González, Fabio

    2015-12-01

    Convolutional neural networks (CNN) have been very successful at addressing different computer vision tasks thanks to their ability to learn image representations directly from large amounts of labeled data. Features learned from a dataset can be used to represent images from a different dataset via an approach called transfer learning. In this paper we apply transfer learning to the challenging task of medulloblastoma tumor differentiation. We compare two different CNN models which were previously trained in two different domains (natural and histopathology images). The first CNN is a state-of-the-art approach in computer vision, a large and deep CNN with 16-layers, Visual Geometry Group (VGG) CNN. The second (IBCa-CNN) is a 2-layer CNN trained for invasive breast cancer tumor classification. Both CNNs are used as visual feature extractors of histopathology image regions of anaplastic and non-anaplastic medulloblastoma tumor from digitized whole-slide images. The features from the two models are used, separately, to train a softmax classifier to discriminate between anaplastic and non-anaplastic medulloblastoma image regions. Experimental results show that the transfer learning approach produce competitive results in comparison with the state of the art approaches for IBCa detection. Results also show that features extracted from the IBCa-CNN have better performance in comparison with features extracted from the VGG-CNN. The former obtains 89.8% while the latter obtains 76.6% in terms of average accuracy.

  18. 4-1BB Aptamer-Based Immunomodulation Enhances the Therapeutic Index of Radiation Therapy in Murine Tumor Models

    Energy Technology Data Exchange (ETDEWEB)

    Benaduce, Ana Paula; Brenneman, Randall; Schrand, Brett; Pollack, Alan; Gilboa, Eli; Ishkanian, Adrian, E-mail: aishkanian@med.miami.edu

    2016-10-01

    Purpose: To report a novel strategy using oligonucleotide aptamers to 4-1BB as an alternate method for costimulation, and show that combinatorial therapy with radiation improves the therapeutic ratio over equivalent monoclonal antibodies. Methods and Materials: Subcutaneous 4T1 (mouse mammary carcinoma) tumors were established (approximately 100 mm{sup 3}), and a radiation therapy (RT) dose/fractionation schedule that optimally synergizes with 4-1BB monoclonal antibody (mAb) was identified. Comparable tumor control and animal survival was observed when either 4-1BB antibody or aptamer were combined with RT using models of breast cancer and melanoma (4T1 and B16-F10). Off-target CD8{sup +} T-cell toxicity was evaluated by quantification of CD8{sup +} T cells in livers and spleens of treated animals. Results: When combined with 4-1BB mAb, significant differences in tumor control were observed by varying RT dose and fractionation schedules. Optimal synergy between RT and 4-1BB mAb was observed at 5 Gy × 6. Testing 4-1BB mAb and aptamer independently using the optimal RT (5 Gy × 6 for 4T1/Balb/c and 12 Gy × 1 for B16/C57BL6J mouse models) revealed equivalent tumor control using 4-1BB aptamer and 4-1BB mAb. 4-1BB mAb, but not 4-1BB aptamer-treated animals, exhibited increased lymphocytic liver infiltrates and increased splenic and liver CD8{sup +} T cells. Conclusions: Radiation therapy synergizes with 4-1BB mAb, and this effect is dependent on RT dose and fractionation. Tumor control by 4-1BB aptamer is equivalent to 4-1BB mAb when combined with optimal RT dose, without eliciting off-target liver and spleen CD8{sup +} expansion. 4-1BB aptamer-based costimulation affords a comparable and less toxic strategy to augment RT-mediated tumor control.

  19. Analysis of the relationship between tumor dose inhomogeneity and local control in patients with skull base chordoma

    International Nuclear Information System (INIS)

    Terahara, Atsuro; Niemierko, Andrzej; Goitein, Michael; Finkelstein, Dianne; Hug, Eugen; Liebsch, Norbert; O'Farrell, Desmond; Lyons, Sue; Munzenrider, John

    1999-01-01

    Purpose: When irradiating a tumor that abuts or displaces any normal structures, the dose constraints to those structures (if lower than the prescribed dose) may cause dose inhomogeneity in the tumor volume at the tumor-critical structure interface. The low-dose region in the tumor volume may be one of the reasons for local failure. The aim of this study is to quantitate the effect of tumor dose inhomogeneity on local control and recurrence-free survival in patients with skull base chordoma. Methods and Materials: 132 patients with skull base chordoma were treated with combined photon and proton irradiation between 1978 and 1993. This study reviews 115 patients whose dose-volume data and follow-up data are available. The prescribed doses ranged from 66.6 Cobalt-Gray-Equivalent (CGE) to 79.2 CGE (median of 68.9 CGE). The dose to the optic structures (optic nerves and chiasma), the brain stem surface, and the brain stem center was limited to 60, 64, and 53 CGE, respectively. We used the dose-volume histogram data derived with the three-dimensional treatment planning system to evaluate several dose-volume parameters including the Equivalent Uniform Dose (EUD). We also analyzed several other patient and treatment factors in relation to local control and recurrence-free survival. Results: Local failure developed in 42 of 115 patients, with the actuarial local control rates at 5 and 10 years being 59% and 44%. Gender was a significant predictor for local control with the prognosis in males being significantly better than that in females (P 0.004, hazard ratio = 2.3). In a Cox univariate analysis, with stratification by gender, the significant predictors for local control (at the probability level of 0.05) were EUD, the target volume, the minimum dose, and the D 5cc dose. The prescribed dose, histology, age, the maximum dose, the mean dose, the median dose, the D 90% dose, and the overall treatment time were not significant factors. In a Cox multivariate analysis, the

  20. A curcumin-based TPA four-branched copper(II) complex probe for in vivo early tumor detection

    Energy Technology Data Exchange (ETDEWEB)

    Pi, Zongxin [Department of Chemical and Chemical Engineering, Hefei Normal University, Hefei 230001 (China); Wang, Jiafeng; Jiang, Bo [Department of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038 (China); Cheng, Gang [Department of Chemical and Chemical Engineering, Hefei Normal University, Hefei 230001 (China); Zhou, Shuangsheng, E-mail: zshuangsheng@126.com [Department of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038 (China); Center of Modern Experimental Technology, Anhui University, Hefei 230038 (China)

    2015-01-01

    A multibranched Cu(II) complex CuL{sub 2} curcumin-based was synthesized and characterized by single-crystal X-ray diffraction analysis. The photophysical properties of the complex have been investigated both experimentally and theoretically. The results show that the target complex exhibits higher quantum yield and larger two-photon absorption (TPA) cross-section in the near infrared (NIR) region compared with its free ligand. The cell imaging studies in vitro and in vivo reveal that the complex shows good photostability and excellent tumor targeting capability to tested cancerous cells, which can be potentially used for early tumor detection. - Graphical abstract: A multibranched Cu(II) complex was prepared from curcumin. The photophysical properties of the obtained complex have been investigated. The results exhibit that the complex has high capability to test cancerous cells and can distinguish between the cancerous and noncancerous cells, which should be potentially used for early tumor detection. - Highlights: • A novel multi-branched copper complex was synthesized. • The obtained compounds exhibited obvious TPA in high polar solvents. • The complex is a low toxicity at low-micromolar concentrations. • The complex exhibits larger TPA cross-section and brighter TPF imaging. • The complex has excellent targeting capability to tested cancerous cells.

  1. Prediction of the microsurgical window for skull-base tumors by advanced three-dimensional multi-fusion volumetric imaging

    International Nuclear Information System (INIS)

    Oishi, Makoto; Fukuda, Masafumi; Saito, Akihiko; Hiraishi, Tetsuya; Fujii, Yukihiko; Ishida, Go

    2011-01-01

    The surgery of skull base tumors (SBTs) is difficult due to the complex and narrow surgical window that is restricted by the cranium and important structures. The utility of three-dimensional multi-fusion volumetric imaging (3-D MFVI) for visualizing the predicted window for SBTs was evaluated. Presurgical simulation using 3-D MFVI was performed in 32 patients with SBTs. Imaging data were collected from computed tomography, magnetic resonance imaging, and digital subtraction angiography. Skull data was processed to imitate actual bone resection and integrated with various structures extracted from appropriate imaging modalities by image-analyzing software. The simulated views were compared with the views obtained during surgery. All craniotomies and bone resections except opening of the acoustic canal in 2 patients were performed as simulated. The simulated window allowed observation of the expected microsurgical anatomies including tumors, vasculatures, and cranial nerves, through the predicted operative window. We could not achieve the planned tumor removal in only 3 patients. 3-D MFVI afforded high quality images of the relevant microsurgical anatomies during the surgery of SBTs. The intraoperative deja-vu effect of the simulation increased the confidence of the surgeon in the planned surgical procedures. (author)

  2. Hydrogel-based 3D model of patient-derived prostate xenograft tumors suitable for drug screening.

    Science.gov (United States)

    Fong, Eliza L S; Martinez, Mariane; Yang, Jun; Mikos, Antonios G; Navone, Nora M; Harrington, Daniel A; Farach-Carson, Mary C

    2014-07-07

    The lack of effective therapies for bone metastatic prostate cancer (PCa) underscores the need for accurate models of the disease to enable the discovery of new therapeutic targets and to test drug sensitivities of individual tumors. To this end, the patient-derived xenograft (PDX) PCa model using immunocompromised mice was established to model the disease with greater fidelity than is possible with currently employed cell lines grown on tissue culture plastic. However, poorly adherent PDX tumor cells exhibit low viability in standard culture, making it difficult to manipulate these cells for subsequent controlled mechanistic studies. To overcome this challenge, we encapsulated PDX tumor cells within a three-dimensional hyaluronan-based hydrogel and demonstrated that the hydrogel maintains PDX cell viability with continued native androgen receptor expression. Furthermore, a differential sensitivity to docetaxel, a chemotherapeutic drug, was observed as compared to a traditional PCa cell line. These findings underscore the potential impact of this novel 3D PDX PCa model as a diagnostic platform for rapid drug evaluation and ultimately push personalized medicine toward clinical reality.

  3. Correlation of a hypoxia based tumor control model with observed local control rates in nasopharyngeal carcinoma treated with chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Avanzo, Michele; Stancanello, Joseph; Franchin, Giovanni; Sartor, Giovanna; Jena, Rajesh; Drigo, Annalisa; Dassie, Andrea; Gigante, Marco; Capra, Elvira [Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Research and Clinical Collaborations, Siemens Healthcare, Erlangen 91052 (Germany); Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ (United Kingdom); Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy)

    2010-04-15

    Purpose: To extend the application of current radiation therapy (RT) based tumor control probability (TCP) models of nasopharyngeal carcinoma (NPC) to include the effects of hypoxia and chemoradiotherapy (CRT). Methods: A TCP model is described based on the linear-quadratic model modified to account for repopulation, chemotherapy, heterogeneity of dose to the tumor, and hypoxia. Sensitivity analysis was performed to determine which parameters exert the greatest influence on the uncertainty of modeled TCP. On the basis of the sensitivity analysis, the values of specific radiobiological parameters were set to nominal values reported in the literature for NPC or head and neck tumors. The remaining radiobiological parameters were determined by fitting TCP to clinical local control data from published randomized studies using both RT and CRT. Validation of the model was performed by comparison of estimated TCP and average overall local control rate (LCR) for 45 patients treated at the institution with conventional linear-accelerator-based or helical tomotherapy based intensity-modulated RT and neoadjuvant chemotherapy. Results: Sensitivity analysis demonstrates that the model is most sensitive to the radiosensitivity term {alpha} and the dose per fraction. The estimated values of {alpha} and OER from data fitting were 0.396 Gy{sup -1} and 1.417. The model estimate of TCP (average 90.9%, range 26.9%-99.2%) showed good correlation with the LCR (86.7%). Conclusions: The model implemented in this work provides clinicians with a useful tool to predict the success rate of treatment, optimize treatment plans, and compare the effects of multimodality therapy.

  4. Correlation of a hypoxia based tumor control model with observed local control rates in nasopharyngeal carcinoma treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    Avanzo, Michele; Stancanello, Joseph; Franchin, Giovanni; Sartor, Giovanna; Jena, Rajesh; Drigo, Annalisa; Dassie, Andrea; Gigante, Marco; Capra, Elvira

    2010-01-01

    Purpose: To extend the application of current radiation therapy (RT) based tumor control probability (TCP) models of nasopharyngeal carcinoma (NPC) to include the effects of hypoxia and chemoradiotherapy (CRT). Methods: A TCP model is described based on the linear-quadratic model modified to account for repopulation, chemotherapy, heterogeneity of dose to the tumor, and hypoxia. Sensitivity analysis was performed to determine which parameters exert the greatest influence on the uncertainty of modeled TCP. On the basis of the sensitivity analysis, the values of specific radiobiological parameters were set to nominal values reported in the literature for NPC or head and neck tumors. The remaining radiobiological parameters were determined by fitting TCP to clinical local control data from published randomized studies using both RT and CRT. Validation of the model was performed by comparison of estimated TCP and average overall local control rate (LCR) for 45 patients treated at the institution with conventional linear-accelerator-based or helical tomotherapy based intensity-modulated RT and neoadjuvant chemotherapy. Results: Sensitivity analysis demonstrates that the model is most sensitive to the radiosensitivity term α and the dose per fraction. The estimated values of α and OER from data fitting were 0.396 Gy -1 and 1.417. The model estimate of TCP (average 90.9%, range 26.9%-99.2%) showed good correlation with the LCR (86.7%). Conclusions: The model implemented in this work provides clinicians with a useful tool to predict the success rate of treatment, optimize treatment plans, and compare the effects of multimodality therapy.

  5. Reactive oxygen species responsive drug releasing nanoparticle based on chondroitin sulfate-anthocyanin nanocomplex for efficient tumor therapy.

    Science.gov (United States)

    Jeong, Dooyong; Bae, Byoung-Chan; Park, Sin-Jung; Na, Kun

    2016-01-28

    To develop a reactive oxygen species (ROS) sensitive drug carrier, a chondroitin sulfate (CS)-anthocyanin (ATC) based nanocomplex was developed. Doxorubicin hydrochloride (DOX) was loaded in the CS-ATC nanocomplex (CS-ATC-DOX) via intermolecular stacking interaction. The nanocomplex was fabricated by a simple mixing method in the aqueous phase. The morphology and size of CS-ATC-DOX were determined by ATC content. In the group with 1.5mg/ml of ATC loaded CS-ATC-DOX (CS-ATC2-DOX), the drug content and loading efficiency were 8.5% and 99.1%, respectively. The ROS sensitive drug release of CS-ATC2-DOX was confirmed under in vitro physiological conditions. The results demonstrated that 1.67 times higher DOX release occurred in CS-ATC2-DOX for 48h compared to CS-DOX (ATC absent sample). Drug release and nanocomplex destruction were induced by ROS mediated ATC degradation. We determined that 66.7% of ROS was scavenged by CS-ATC2-DOX. Additionally, an HCT-116 tumor bearing animal model was used to confirm ROS sensitive therapeutic effects of CS-ATC2-DOX. The results indicate that DOX was released from the intravenously injected CS-ATC2-DOX in the tumor tissue. Thus, nuclei shrinkage and dead cells were observed in H&E staining and TUNEL assay, respectively. These data suggest that the tumor growth was effectively inhibited. This study means that CS-ATC2-DOX has potential in improving tumor therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. A Comparison of Amplitude-Based and Phase-Based Positron Emission Tomography Gating Algorithms for Segmentation of Internal Target Volumes of Tumors Subject to Respiratory Motion

    International Nuclear Information System (INIS)

    Jani, Shyam S.; Robinson, Clifford G.; Dahlbom, Magnus; White, Benjamin M.; Thomas, David H.; Gaudio, Sergio; Low, Daniel A.; Lamb, James M.

    2013-01-01

    Purpose: To quantitatively compare the accuracy of tumor volume segmentation in amplitude-based and phase-based respiratory gating algorithms in respiratory-correlated positron emission tomography (PET). Methods and Materials: List-mode fluorodeoxyglucose-PET data was acquired for 10 patients with a total of 12 fluorodeoxyglucose-avid tumors and 9 lymph nodes. Additionally, a phantom experiment was performed in which 4 plastic butyrate spheres with inner diameters ranging from 1 to 4 cm were imaged as they underwent 1-dimensional motion based on 2 measured patient breathing trajectories. PET list-mode data were gated into 8 bins using 2 amplitude-based (equal amplitude bins [A1] and equal counts per bin [A2]) and 2 temporal phase-based gating algorithms. Gated images were segmented using a commercially available gradient-based technique and a fixed 40% threshold of maximum uptake. Internal target volumes (ITVs) were generated by taking the union of all 8 contours per gated image. Segmented phantom ITVs were compared with their respective ground-truth ITVs, defined as the volume subtended by the tumor model positions covering 99% of breathing amplitude. Superior-inferior distances between sphere centroids in the end-inhale and end-exhale phases were also calculated. Results: Tumor ITVs from amplitude-based methods were significantly larger than those from temporal-based techniques (P=.002). For lymph nodes, A2 resulted in ITVs that were significantly larger than either of the temporal-based techniques (P<.0323). A1 produced the largest and most accurate ITVs for spheres with diameters of ≥2 cm (P=.002). No significant difference was shown between algorithms in the 1-cm sphere data set. For phantom spheres, amplitude-based methods recovered an average of 9.5% more motion displacement than temporal-based methods under regular breathing conditions and an average of 45.7% more in the presence of baseline drift (P<.001). Conclusions: Target volumes in images generated

  7. Nanoroughened adhesion-based capture of circulating tumor cells with heterogeneous expression and metastatic characteristics

    International Nuclear Information System (INIS)

    Chen, Weiqiang; Allen, Steven G.; Reka, Ajaya Kumar; Qian, Weiyi; Han, Shuo; Zhao, Jianing; Bao, Liwei; Keshamouni, Venkateshwar G.; Merajver, Sofia D.; Fu, Jianping

    2016-01-01

    Circulating tumor cells (CTCs) have shown prognostic relevance in many cancer types. However, the majority of current CTC capture methods rely on positive selection techniques that require a priori knowledge about the surface protein expression of disseminated CTCs, which are known to be a dynamic population. We developed a microfluidic CTC capture chip that incorporated a nanoroughened glass substrate for capturing CTCs from blood samples. Our CTC capture chip utilized the differential adhesion preference of cancer cells to nanoroughened etched glass surfaces as compared to normal blood cells and thus did not depend on the physical size or surface protein expression of CTCs. The microfluidic CTC capture chip was able to achieve a superior capture yield for both epithelial cell adhesion molecule positive (EpCAM+) and EpCAM- cancer cells in blood samples. Additionally, the microfluidic CTC chip captured CTCs undergoing transforming growth factor beta-induced epithelial-to-mesenchymal transition (TGF-β-induced EMT) with dynamically down-regulated EpCAM expression. In a mouse model of human breast cancer using EpCAM positive and negative cell lines, the number of CTCs captured correlated positively with the size of the primary tumor and was independent of their EpCAM expression. Furthermore, in a syngeneic mouse model of lung cancer using cell lines with differential metastasis capability, CTCs were captured from all mice with detectable primary tumors independent of the cell lines’ metastatic ability. The microfluidic CTC capture chip using a novel nanoroughened glass substrate is broadly applicable to capturing heterogeneous CTC populations of clinical interest independent of their surface marker expression and metastatic propensity. We were able to capture CTCs from a non-metastatic lung cancer model, demonstrating the potential of the chip to collect the entirety of CTC populations including subgroups of distinct biological and phenotypical properties. Further

  8. Dendritic cell-based vaccines for the therapy of experimental tumors

    Czech Academy of Sciences Publication Activity Database

    Piasecka, E.P.; Indrová, Marie

    2010-01-01

    Roč. 2, č. 2 (2010), s. 257-268 ISSN 1750-743X R&D Projects: GA AV ČR IAA500520807; GA ČR GA301/09/1024; GA MZd NS10660 Grant - others:Polish Ministry of Science and Higher Education(PL) NN401235334 Institutional research plan: CEZ:AV0Z50520514 Keywords : dendritic cells * preparation of vaccines * experimental tumors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.542, year: 2010

  9. Vatuximab(Trademark): Optimizing Therapeutic Strategies for Prostate Cancer Based on Dynamic MR Tumor Oximetry

    Science.gov (United States)

    2010-01-01

    159: 621-631, 2003. 37. Bourke , V. A., Zhao, D., Gilio, J., Chang, C.-H., Jiang, L., Hahn, E. W., and Mason, R. P. Correlation of Radiation...probe: comparison with a paired survival assay. Radiat Res, 158, 167-73 (2002) 27. Gu, Y. Q., V. A. Bourke , J. G. Kim, A. Constantinescu, R. P. Mason...Res. 1998; 150: 549–556. 10. Bourke VA, Zhao D, Gilio J, Chang C-H, Jiang L, Hahn EW, Mason RP. Correlation of radiation response with tumor oxygen

  10. High hydrostatic pressure affects antigenic pool in tumor cells: Implication for dendritic cell-based cancer immunotherapy.

    Science.gov (United States)

    Urbanova, Linda; Hradilova, Nada; Moserova, Irena; Vosahlikova, Sarka; Sadilkova, Lenka; Hensler, Michal; Spisek, Radek; Adkins, Irena

    2017-07-01

    High hydrostatic pressure (HHP) can be used to generate dendritic cell (DC)-based active immunotherapy for prostate, lung and ovarian cancer. We showed here that HHP treatment of selected human cancer cell lines leads to a degradation of tumor antigens which depends on the magnitude of HHP applied and on the cancer cell line origin. Whereas prostate or ovarian cell lines displayed little protein antigen degradation with HHP treatment up to 300MPa after 2h, tumor antigens are hardly detected in lung cancer cell line after treatment with HHP 250MPa at the same time. On the other hand, quick reduction of tumor antigen-coding mRNA was observed at HHP 200MPa immediately after treatment in all cell lines tested. To optimize the DC-based active cellular therapy protocol for HHP-sensitive cell lines the immunogenicity of HHP-treated lung cancer cells at 150, 200 and 250MPa was compared. Lung cancer cells treated with HHP 150MPa display characteristics of immunogenic cell death, however cells are not efficiently phagocytosed by DC. Despite induction of the highest number of antigen-specific CD8 + T cells, 150 MPa-treated lung cancer cells survive in high numbers. This excludes their use in DC vaccine manufacturing. HHP of 200MPa treatment of lung cancer cells ensures the optimal ratio of efficient immunogenic killing and delivery of protein antigens in DC. These results represent an important pre-clinical data for generation of immunogenic killed lung cancer cells in ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa). Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  11. Improvement of Antitumor Therapies Based on Vaccines and Immune-Checkpoint Inhibitors by Counteracting Tumor-Immunostimulation

    Directory of Open Access Journals (Sweden)

    Paula Chiarella

    2018-01-01

    Full Text Available Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth. Herein, we extended those former observations to weak spontaneous murine tumors growing in pre-immunized, immune-competent and immune-depressed mice. Furthermore, we demonstrated that the interaction of specifical T cells and target tumor cells at low stimulatory ratios enhanced the production of chemokines aimed to recruit macrophages at the tumor site, which, upon activation of toll-like receptor 4 and p38 signaling pathways, would recruit and activate more macrophages and other inflammatory cells which would produce growth-stimulating signals leading to an accelerated tumor growth. On this basis, the paradoxical effects achieved by immunological therapies on growing tumors could be explained depending upon where the therapy-induced IR stands on the biphasic IR curve at each stage of tumor growth. At stages where tumor growth was enhanced (medium and large-sized tumors, counteraction of the tumor-immunostimulatory effect with anti-inflammatory strategies or, more efficiently, with selective inhibitors of p38 signaling pathways enabled the otherwise tumor-promoting immunological strategies to produce significant inhibition of tumor growth.

  12. Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design.

    Science.gov (United States)

    Castaño-Vinyals, Gemma; Aragonés, Nuria; Pérez-Gómez, Beatriz; Martín, Vicente; Llorca, Javier; Moreno, Victor; Altzibar, Jone M; Ardanaz, Eva; de Sanjosé, Sílvia; Jiménez-Moleón, José Juan; Tardón, Adonina; Alguacil, Juan; Peiró, Rosana; Marcos-Gragera, Rafael; Navarro, Carmen; Pollán, Marina; Kogevinas, Manolis

    2015-01-01

    We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  13. 3D model-based documentation with the Tumor Therapy Manager (TTM) improves TNM staging of head and neck tumor patients.

    Science.gov (United States)

    Pankau, Thomas; Wichmann, Gunnar; Neumuth, Thomas; Preim, Bernhard; Dietz, Andreas; Stumpp, Patrick; Boehm, Andreas

    2015-10-01

    Many treatment approaches are available for head and neck cancer (HNC), leading to challenges for a multidisciplinary medical team in matching each patient with an appropriate regimen. In this effort, primary diagnostics and its reliable documentation are indispensable. A three-dimensional (3D) documentation system was developed and tested to determine its influence on interpretation of these data, especially for TNM classification. A total of 42 HNC patient data sets were available, including primary diagnostics such as panendoscopy, performed and evaluated by an experienced head and neck surgeon. In addition to the conventional panendoscopy form and report, a 3D representation was generated with the "Tumor Therapy Manager" (TTM) software. These cases were randomly re-evaluated by 11 experienced otolaryngologists from five hospitals, half with and half without the TTM data. The accuracy of tumor staging was assessed by pre-post comparison of the TNM classification. TNM staging showed no significant differences in tumor classification (T) with and without 3D from TTM. However, there was a significant decrease in standard deviation from 0.86 to 0.63 via TTM ([Formula: see text]). In nodal staging without TTM, the lymph nodes (N) were significantly underestimated with [Formula: see text] classes compared with [Formula: see text] with TTM ([Formula: see text]). Likewise, the standard deviation was reduced from 0.79 to 0.69 ([Formula: see text]). There was no influence of TTM results on the evaluation of distant metastases (M). TNM staging was more reproducible and nodal staging more accurate when 3D documentation of HNC primary data was available to experienced otolaryngologists. The more precise assessment of the tumor classification with TTM should provide improved decision-making concerning therapy, especially within the interdisciplinary tumor board.

  14. A consumer study of Danish entire male pigs

    DEFF Research Database (Denmark)

    Godt, Jannik; Kristensen, Kai; Poulsen, Carsten Stig

    1996-01-01

    made in-home by consumers, thus bringing the analysis out of the laboratory and into the market place. The vast majority of the population of uncastrated male pigs have low concentrations of skatole and androstenone. The cutlets that were evaluated in this study were selected from uncastrated male pigs...... on a number of castrated male pigs and gilts. No difference was found in the way the odour components affected the eating quality determined by men and women. A total of 5.4% of the consumers in the study reacted negatively in their evaluation of the eating quality of the cutlets selected for the study......Former studies of the unpleasant odour of meat from certain uncastrated male pigs have been based mainly on evaluations made by trained sensory panellists. This study analyses the effect of the two dominating male pig odour components, skatole and androstenone, on the evaluation of eating quality...

  15. A Consumer Study of Danish Entire Male Pigs

    DEFF Research Database (Denmark)

    Poulsen, Carsten Stig; Godt, J.; Kristensen, K.

    1996-01-01

    Former studies of the unpleasant odour of meat from certain uncastrated male pigs have been based mainly on evaluations made by trained sensory panellists. This study analyses the effect of the two dominating male pig odour components, skatole and androstenone, on the evaluation of eating quality...... made in-home by consumers, thus bringing the analysis out of the laboratory and into the market place. The vast majority of the population of uncastrated male pigs have low concentrations of skatole and androstenone. The cutlets that were evaluated in this study were selected from uncastrated male pigs...... on a number of castrated male pigs and gilts. No difference was found in the way the odour components affected the eating quality determined by men and women. A total of 5.4% of the consumers in the study reacted negatively in their evaluation of the eating quality of the cutlets selected for the study...

  16. Imaging probe for tumor malignancy

    Science.gov (United States)

    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.

  17. Enhancement of Tumor-Specific T Cell–Mediated Immunity in Dendritic Cell–Based Vaccines by Mycobacterium tuberculosis Heat Shock Protein X

    Science.gov (United States)

    Jung, In Duk; Shin, Sung Jae; Lee, Min-Goo; Kang, Tae Heung; Han, Hee Dong; Lee, Seung Jun; Kim, Woo Sik; Kim, Hong Min; Park, Won Sun; Kim, Han Wool; Yun, Cheol-Heui; Lee, Eun Kyung; Wu, T.-C.

    2014-01-01

    Despite the potential for stimulation of robust antitumor immunity by dendritic cells (DCs), clinical applications of DC-based immunotherapy are limited by the low potency in generating tumor Ag-specific T cell responses. Therefore, optimal conditions for generating potent immunostimulatory DCs that overcome tolerance and suppression are key factors in DC-based tumor immunotherapy. In this study, we demonstrate that use of the Mycobacterium tuberculosis heat shock protein X (HspX) as an immunoadjuvant in DC-based tumor immunotherapy has significant potential in therapeutics. In particular, the treatment aids the induction of tumor-reactive T cell responses, especially tumor-specific CTLs. The HspX protein induces DC maturation and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, and IFN-β) through TLR4 binding partially mediated by both the MyD88 and the TRIF signaling pathways. We employed two models of tumor progression and metastasis to evaluate HspX-stimulated DCs in vivo. The administration of HspX-stimulated DCs increased the activation of naive T cells, effectively polarizing the CD4+ and CD8+ T cells to secrete IFN-γ, as well as enhanced the cytotoxicity of splenocytes against HPV-16 E7 (E7)–expressing TC-1 murine tumor cells in therapeutic experimental animals. Moreover, the metastatic capacity of B16-BL6 melanoma cancer cells toward the lungs was remarkably attenuated in mice that received HspX-stimulated DCs. In conclusion, the high therapeutic response rates with tumor-targeted Th1-type T cell immunity as a result of HspX-stimulated DCs in two models suggest that HspX harnesses the exquisite immunological power and specificity of DCs for the treatment of tumors. PMID:24990079

  18. Optimization of the fractionated irradiation scheme considering physical doses to tumor and organ at risk based on dose–volume histograms

    Energy Technology Data Exchange (ETDEWEB)

    Sugano, Yasutaka [Graduate School of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Mizuta, Masahiro [Laboratory of Advanced Data Science, Information Initiative Center, Hokkaido University, Kita-11, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0811 (Japan); Takao, Seishin; Shirato, Hiroki; Sutherland, Kenneth L. [Department of Radiation Medicine, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-8638 (Japan); Date, Hiroyuki, E-mail: date@hs.hokudai.ac.jp [Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan)

    2015-11-15

    Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.

  19. OS03.4 Gammaknife versus Linac based (EDGE) radiosurgery (SRS) for patients with limited brain metastases (BMS) from different solid tumor: a phase III randomized trial.

    Science.gov (United States)

    Scorsetti, M.; Navarria, P.; Ascolese, A.; Clerici, E.; Mancosu, P.; Picozzi, P.; Pecchioli, G.; Franzese, C.; Reggiori, G.; Tomatis, S.

    2017-01-01

    Abstract Introduction: Radiosurgery is an emerging terapeutich approach for the treatment of brain metastases (BMs), considering the effective local control obtained without neurological impairment. Different technological modalities have been used: Gammaknife, Cybernife, or Linac with comparable results and different incidence of symptomatic radionecrosis. To date no comparative randomized studies have been published on this matter. We draw this randomized phase III trial with the aim to evaluate incidence of symptomatic radionecrosis using gamma knife radiosurgery versus linac based (EDGE) radiosurgery. Local control (LC) rate and patients overall survival (OS) were assessed as well. Materials: Patients with limited BMs (up to 4) from different solid tumors, except SCLC or hematologic malignancies, were enrolled. Inclusion criteria were a histopatological diagnosis of malignant primary tumor, a KPS ≥70, RPA class I-II, and BMs with maximum diameter ≤3 cm and/or with a total tumor volume <30 cm3. The total dose prescribed was 24 Gy for BMs ≤ 20 mm or 4.2 cm3, and 20 Gy for BMs 21–30 mm or volume <14.1 cm3 as suggested by RTOG guidelines. Clinical outcome was evaluated by neurological examination and MRI at 2 months after SRS and then every 3 months. The radionecrosis was considered the presence of central hypodensity and peripheral enhancement on T1-weighted post-contrast imaging, with edema on T2-weighted sequences and a clear lack of perfusion without any nodular highly vascularized area within the contrast enhanced lesion on perfusion MRI. Local progression was defined as radiographic increase of the enhancing abnormality in the irradiated volume on serial MR imaging, and distant failure by the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume. Results: From October 2014 to December 2015, 101 consecutives patients of the expected 250, for 167 BMs treated, were evaluated. The most common primary

  20. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

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

  1. Sapphire implant based neuro-complex for deep-lying brain tumors phototheranostics

    Science.gov (United States)

    Sharova, A. S.; Maklygina, YU S.; Yusubalieva, G. M.; Shikunova, I. A.; Kurlov, V. N.; Loschenov, V. B.

    2018-01-01

    The neuro-complex as a combination of sapphire implant optical port and osteoplastic biomaterial "Collapan" as an Aluminum phthalocyanine nanoform photosensitizer (PS) depot was developed within the framework of this study. The main goals of such neuro-complex are to provide direct access of laser radiation to the brain tissue depth and to transfer PS directly to the pathological tissue location that will allow multiple optical phototheranostics of the deep-lying tumor region without repeated surgical intervention. The developed complex spectral-optical properties research was carried out by photodiagnostics method using the model sample: a brain tissue phantom. The optical transparency of sapphire implant allows obtaining a fluorescent signal with high accuracy, comparable to direct measurement "in contact" with the tissue.

  2. Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route

    International Nuclear Information System (INIS)

    Jain, Darshana S.; Bajaj, Amrita N.; Athawale, Rajani B.; Shikhande, Shruti S.; Pandey, Abhijeet; Goel, Peeyush N.; Gude, Rajiv P.; Patil, Satish; Raut, Preeti

    2016-01-01

    Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors. - Highlights: • The present investigation explores intra-nasal route as potential route for targeting brain tumor. • Thermosensitive nanodispersion has been formulated for enhancing nasal residence time. • PLA nanoparticles enhance penetration into the brain owing to hydrophobic nature and small size

  3. Short- and long-term outcomes after enucleation of pancreatic tumors: An evidence-based assessment.

    Science.gov (United States)

    Zhou, Yanming; Zhao, Min; Wu, Lupeng; Ye, Feng; Si, Xiaoying

    Enucleation of pancreatic tumors is rarely performed. The aim of this study was to evaluate the published evidence for its short- and long-term outcomes. PubMed (MEDLINE) and EMBASE databases were searched from 1990 to March 2016. Studies including at least ten patients who underwent enucleation of pancreatic lesions were included. Data on the outcomes were synthesized and meta-analyzed where appropriate. Twenty-seven studies involving 1316 patients were included in the systematic review. The postoperative mortality was 0.3%, and the postoperative morbidity was 50.3%, mainly represented by pancreatic fistula (38.1%). Endocrine insufficiency, exocrine insufficiency and tumor recurrence was observed in 2.4%, 1.1% and 2.3% of the patients respectively. Compared with typical resection, the operation time, blood loss, length of hospital stay, and the incidence of endocrine and exocrine insufficiency were all significantly reduced after enucleation. The occurrence of pancreatic fistula was significantly higher in enucleation group, but overall morbidity, the reoperation rate and mortality were comparable between the two groups. There was no significant difference in disease recurrence between the two groups. Compared with central pancreatectomy, enucleation had a shorter operation time, lower blood loss, less morbidity, and better pancreatic function. Compared with open enucleation, minimally invasive enucleation had a shorter operation time and a shorter length of hospital stay. Enucleation is an appropriate surgical procedure in selected patients with benign or low-malignant lesions of the pancreas. The benefits of minimally invasive approach need to be validated in further investigations with larger groups of patients. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  4. Generation of Multicellular Tumor Spheroids with Microwell-Based Agarose Scaffolds for Drug Testing.

    Directory of Open Access Journals (Sweden)

    Xue Gong

    Full Text Available Three dimensional multicellular aggregate, also referred to as cell spheroid or microtissue, is an indispensable tool for in vitro evaluating antitumor activity and drug efficacy. Compared with classical cellular monolayer, multicellular tumor spheroid (MCTS offers a more rational platform to predict in vivo drug efficacy and toxicity. Nevertheless, traditional processing methods such as plastic dish culture with nonadhesive surfaces are regularly time-consuming, laborious and difficult to provide uniform-sized spheroids, thus causing poor reproducibility of experimental data and impeding high-throughput drug screening. In order to provide a robust and effective platform for in vitro drug evaluation, we present an agarose scaffold prepared with the template containing uniform-sized micro-wells in commercially available cell culture plates. The agarose scaffold allows for good adjustment of MCTS size and large-scale production of MCTS. Transparent agarose scaffold also allows for monitoring of spheroid formation under an optical microscopy. The formation of MCTS from MCF-7 cells was prepared using different-size-well templates and systematically investigated in terms of spheroid growth curve, circularity, and cell viability. The doxorubicin cytotoxicity against MCF-7 spheroid and MCF-7 monolayer cells was compared. The drug penetration behavior, cell cycle distribution, cell apoptosis, and gene expression were also evaluated in MCF-7 spheroid. The findings of this study indicate that, compared with cellular monolayer, MCTS provides a valuable platform for the assessment of therapeutic candidates in an in vivo-mimic microenvironment, and thus has great potential for use in drug discovery and tumor biology research.

  5. Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Darshana S., E-mail: darshanaj_cup@yahoo.com [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Bajaj, Amrita N. [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Athawale, Rajani B., E-mail: rajani.athawale@gmail.com [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Shikhande, Shruti S. [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Pandey, Abhijeet [H. R Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra (India); Goel, Peeyush N.; Gude, Rajiv P. [Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410 210 (India); Patil, Satish; Raut, Preeti [Cipla Pvt. Ltd., Vikhroli (West), Mumbai (India)

    2016-06-01

    Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors. - Highlights: • The present investigation explores intra-nasal route as potential route for targeting brain tumor. • Thermosensitive nanodispersion has been formulated for enhancing nasal residence time. • PLA nanoparticles enhance penetration into the brain owing to hydrophobic nature and small size

  6. Optimization of Diagnostic Elisa - Based Tests for the Detection of Auto-Antibodies Against Tumor Antigens in Human Serum

    Directory of Open Access Journals (Sweden)

    Daria Štefatić

    2008-08-01

    Full Text Available Colorectal cancer is one of the most common cancer types worldwide and it continues to be a serious public health problem. Early detection and diagnosis are of great importance in cancer management. At present, diagnostic blood tests are based on the detection of tumor-associated markers such as carcinoembryonic antigen (CEA, the cancer antigen CA19-9 for gastrointestinal cancer, CA15-3 for breast cancer or CA125 for ovarian cancer. The lack of sensitivity and specificity of these markers prevents their general use in cancer screening of an average risk population. Therefore, new cancer biomarkers or better screening methods are necessary to improve the diagnostics of the disease. This study was directed to the optimization of a diagnostic, enzyme linked immunosorbent assay (ELISA based test to identify and validate new serum markers, such as extracellular Protein Kinase A (ecPKA and Nicotinamide A-Meth- yltransferase (NNMT. In this type of assay, the cancer antigens are quantified indirectly - by detecting the presence of auto-antibodies against tumor proteins in human serum. The result of the optimization and validation process was in the case of ecPKA a reproducible and stable assay. In case of NNMT the assay was probably not sensitive enough.

  7. Gross tumor volume (GTV) and clinical target volume (CTV) for radiation therapy of benign skull base tumours

    International Nuclear Information System (INIS)

    Maire, J.P.; Liguoro, D.; San Galli, F.

    2001-01-01

    Skull base tumours represent a out 35 to 40% of all intracranial tumours. There are now many reports in the literature confirming the fact that about 80 to 90% of such tumours are controlled with fractionated radiotherapy. Stereotactic and 3-dimensional treatment planning techniques increase local control and central nervous system tolerance. Definition of the gross tumor volume (GTV) is generally easy with currently available medical imaging systems and computers for 3-dimensional dosimetry. The definition of the clinical target volume (CTV) is more difficult to appreciate: it is defined from the CTV plus a margin, which depends on the histology and anterior therapeutic history of the tumour. It is important to take into account the visible tumour and its possible extension pathways (adjacent bone, holes at the base of skull) and/or an anatomic region (sella turcica + adjacent cavernous sinus). It is necessary to evaluate these volumes with CT Scan and MRI to appreciate tumor extension in a 3-dimensional approach, in order to reduce the risk of marginal recurrences. The aim of this paper is to discuss volume definition as a function of tumour site and tumour type to be irradiated. (authors)

  8. Histological type and grade of breast cancer tumors by parity, age at birth, and time since birth: a register-based study in Norway

    International Nuclear Information System (INIS)

    Albrektsen, Grethe; Heuch, Ivar; Thoresen, Steinar Ø

    2010-01-01

    Some studies have indicated that reproductive factors affect the risk of histological types of breast cancer differently. The long-term protective effect of a childbirth is preceded by a short-term adverse effect. Few studies have examined whether tumors diagnosed shortly after birth have specific histological characteristics. In the present register-based study, comprising information for 22,867 Norwegian breast cancer cases (20-74 years), we examined whether histological type (9 categories) and grade of tumor (2 combined categories) differed by parity or age at first birth. Associations with time since birth were evaluated among 9709 women diagnosed before age 50 years. Chi-square tests were applied for comparing proportions, whereas odds ratios (each histological type vs. ductal, or grade 3-4 vs. grade 1-2) were estimated in polytomous and binary logistic regression analyses. Ductal tumors, the most common histological type, accounted for 81.4% of all cases, followed by lobular tumors (6.3%) and unspecified carcinomas (5.5%). Other subtypes accounted for 0.4%-1.5% of the cases each. For all histological types, the proportions differed significantly by age at diagnoses. The proportion of mucinous and tubular tumors decreased with increasing parity, whereas Paget disease and medullary tumors were most common in women of high parity. An increasing trend with increasing age at first birth was most pronounced for lobular tumors and unspecified carcinomas; an association in the opposite direction was seen in relation to medullary and tubular tumors. In age-adjusted analyses, only the proportions of unspecified carcinomas and lobular tumors decreased significantly with increasing time since first and last birth. However, ductal tumors, and malignant sarcomas, mainly phyllodes tumors, seemed to occur at higher frequency in women diagnosed <2 years after first childbirth. The proportions of medullary tumors and Paget disease were particularly high among women diagnosed 2

  9. Templated dewetting: designing entirely self-organized platforms for photocatalysis.

    Science.gov (United States)

    Altomare, Marco; Nguyen, Nhat Truong; Schmuki, Patrik

    2016-12-01

    Formation and dispersion of metal nanoparticles on oxide surfaces in site-specific or even arrayed configuration are key in various technological processes such as catalysis, photonics, electrochemistry and for fabricating electrodes, sensors, memory devices, and magnetic, optical, and plasmonic platforms. A crucial aspect towards an efficient performance of many of these metal/metal oxide arrangements is a reliable fabrication approach. Since the early works on graphoepitaxy in the 70s, solid state dewetting of metal films on patterned surfaces has been much explored and regarded as a most effective tool to form defined arrays of ordered metal particles on a desired substrate. While templated dewetting has been studied in detail, particularly from a mechanistic perspective on lithographically patterned Si surfaces, the resulting outstanding potential of its applications on metal oxide semiconductors, such as titania, has received only limited attention. In this perspective we illustrate how dewetting and particularly templated dewetting can be used to fabricate highly efficient metal/TiO 2 photocatalyst assemblies e.g. for green hydrogen evolution. A remarkable advantage is that the synthesis of such photocatalysts is completely based on self-ordering principles: anodic self-organized TiO 2 nanotube arrays that self-align to a highest degree of hexagonal ordering are an ideal topographical substrate for a second self-ordering process, that is, templated-dewetting of sputter-deposited metal thin films. The controllable metal/semiconductor coupling delivers intriguing features and functionalities. We review concepts inherent to dewetting and particularly templated dewetting, and outline a series of effective tools that can be synergistically interlaced to reach fine control with nanoscopic precision over the resulting metal/TiO 2 structures (in terms of e.g. high ordering, size distribution, site specific placement, alloy formation) to maximize their photocatalytic

  10. TU-F-CAMPUS-J-03: Elasticity Functions Based On 4DCT Images to Predict Tumor and Normal Tissue Response to Radiation for Patients with Lung Cancers

    International Nuclear Information System (INIS)

    Zhong, H; Li, H; Gordon, J; Chetty, I

    2015-01-01

    Purpose: To investigate radiotherapy outcomes by incorporating 4DCT-based physiological and tumor elasticity functions for lung cancer patients. Methods: 4DCT images were acquired from 28 lung SBRT patients before radiation treatment. Deformable image registration (DIR) was performed from the end-inhale to the end-exhale using a B-Spline-based algorithm (Elastix, an open source software package). The resultant displacement vector fields (DVFs) were used to calculate a relative Jacobian function (RV) for each patient. The computed functions in the lung and tumor regions represent lung ventilation and tumor elasticity properties, respectively. The 28 patients were divided into two groups: 16 with two-year tumor local control (LC) and 12 with local failure (LF). The ventilation and elasticity related RV functions were calculated for each of these patients. Results: The LF patients have larger RV values than the LC patients. The mean RV value in the lung region was 1.15 (±0.67) for the LF patients, higher than 1.06 (±0.59) for the LC patients. In the tumor region, the elasticity-related RV values are 1.2 (±0.97) and 0.86 (±0.64) for the LF and LC patients, respectively. Among the 16 LC patients, 3 have the mean RV values greater than 1.0 in the tumors. These tumors were located near the diaphragm, where the displacements are relatively large.. RV functions calculated in the tumor were better correlated with treatment outcomes than those calculated in the lung. Conclusion: The ventilation and elasticity-related RV functions in the lung and tumor regions were calculated from 4DCT image and the resultant values showed differences between the LC and LF patients. Further investigation of the impact of the displacements on the computed RV is warranted. Results suggest that the RV images might be useful for evaluation of treatment outcome for lung cancer patients

  11. TU-F-CAMPUS-J-03: Elasticity Functions Based On 4DCT Images to Predict Tumor and Normal Tissue Response to Radiation for Patients with Lung Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, H; Li, H; Gordon, J; Chetty, I [Henry Ford Health System, Detroit, MI (United States)

    2015-06-15

    Purpose: To investigate radiotherapy outcomes by incorporating 4DCT-based physiological and tumor elasticity functions for lung cancer patients. Methods: 4DCT images were acquired from 28 lung SBRT patients before radiation treatment. Deformable image registration (DIR) was performed from the end-inhale to the end-exhale using a B-Spline-based algorithm (Elastix, an open source software package). The resultant displacement vector fields (DVFs) were used to calculate a relative Jacobian function (RV) for each patient. The computed functions in the lung and tumor regions represent lung ventilation and tumor elasticity properties, respectively. The 28 patients were divided into two groups: 16 with two-year tumor local control (LC) and 12 with local failure (LF). The ventilation and elasticity related RV functions were calculated for each of these patients. Results: The LF patients have larger RV values than the LC patients. The mean RV value in the lung region was 1.15 (±0.67) for the LF patients, higher than 1.06 (±0.59) for the LC patients. In the tumor region, the elasticity-related RV values are 1.2 (±0.97) and 0.86 (±0.64) for the LF and LC patients, respectively. Among the 16 LC patients, 3 have the mean RV values greater than 1.0 in the tumors. These tumors were located near the diaphragm, where the displacements are relatively large.. RV functions calculated in the tumor were better correlated with treatment outcomes than those calculated in the lung. Conclusion: The ventilation and elasticity-related RV functions in the lung and tumor regions were calculated from 4DCT image and the resultant values showed differences between the LC and LF patients. Further investigation of the impact of the displacements on the computed RV is warranted. Results suggest that the RV images might be useful for evaluation of treatment outcome for lung cancer patients.

  12. Tamoxifen-Containing Eye Drops Successfully Trigger Cre-Mediated Recombination in the Entire Eye.

    Science.gov (United States)

    Schlecht, Anja; Leimbeck, Sarah V; Tamm, Ernst R; Braunger, Barbara M

    2016-01-01

    Embryonic lethality in mice with targeted gene deletion is a major issue that can be circumvented by using Cre-loxP-based animal models. Various inducible Cre systems are available, e.g. such that are activated following tamoxifen treatment, and allow deletion of a specific target gene at any desired time point during the life span of the animal. In this study, we describe the efficiency of topical tamoxifen administration by eye drops using a Cre- reporter mouse strain (R26R). We report that tamoxifen-responsive CAGGCre-ER (TM) mice show a robust Cre- mediated recombination throughout the entire eye.

  13. Nanoelectromechanical switch operating by tunneling of an entire C-60 molecule

    DEFF Research Database (Denmark)

    Danilov, Andrey V.; Hedegård, Per; Golubev, Dimitrii S.

    2008-01-01

    (i) the relative contribution of tunneling, current induced heating and thermal fluctuations to the switching mechanism, (ii) the voltage dependent energy barrier (similar to 100-200 meV) separating the two states of the switch and (iii) the switching attempt frequency, omega(0) corresponding to a 2......We present a solid state single molecule electronic device where switching between two states with different conductance happens predominantly by tunneling of an entire C-60 molecule. This conclusion is based on a novel statistical analysis of similar to 10(5) switching events. The analysis yields...

  14. AlgiMatrix™ based 3D cell culture system as an in-vitro tumor model for anticancer studies.

    Directory of Open Access Journals (Sweden)

    Chandraiah Godugu

    Full Text Available Three-dimensional (3D in-vitro cultures are recognized for recapitulating the physiological microenvironment and exhibiting high concordance with in-vivo conditions. Taking the advantages of 3D culture, we have developed the in-vitro tumor model for anticancer drug screening.Cancer cells grown in 6 and 96 well AlgiMatrix™ scaffolds resulted in the formation of multicellular spheroids in the size range of 100-300 µm. Spheroids were grown in two weeks in cultures without compromising the growth characteristics. Different marketed anticancer drugs were screened by incubating them for 24 h at 7, 9 and 11 days in 3D cultures and cytotoxicity was measured by AlamarBlue® assay. Effectiveness of anticancer drug treatments were measured based on spheroid number and size distribution. Evaluation of apoptotic and anti-apoptotic markers was done by immunohistochemistry and RT-PCR. The 3D results were compared with the conventional 2D monolayer cultures. Cellular uptake studies for drug (Doxorubicin and nanoparticle (NLC were done using spheroids.IC(50 values for anticancer drugs were significantly higher in AlgiMatrix™ systems compared to 2D culture models. The cleaved caspase-3 expression was significantly decreased (2.09 and 2.47 folds respectively for 5-Fluorouracil and Camptothecin in H460 spheroid cultures compared to 2D culture system. The cytotoxicity, spheroid size distribution, immunohistochemistry, RT-PCR and nanoparticle penetration data suggested that in vitro tumor models show higher resistance to anticancer drugs and supporting the fact that 3D culture is a better model for the cytotoxic evaluation of anticancer drugs in vitro.The results from our studies are useful to develop a high throughput in vitro tumor model to study the effect of various anticancer agents and various molecular pathways affected by the anticancer drugs and formulations.

  15. Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes.

    Science.gov (United States)

    Hallet, Julie; Law, Calvin How Lim; Cukier, Moises; Saskin, Refik; Liu, Ning; Singh, Simron

    2015-02-15

    An increased incidence of neuroendocrine tumors (NETs) has been reported worldwide, but the reasons underlying this rise have not been identified. By assessing patterns of metastatic presentation, this study sought to examine the epidemiologic characteristics of NETs and the contribution of early-stage detection to the rising incidence. A population-based retrospective cohort study was conducted with prospectively maintained databases linked at the Institute for Clinical Evaluative Sciences. Adult patients with a NET diagnosis from 1994 to 2009 in Ontario, Canada were included. The main outcomes included the overall and site-specific incidence, proportion of metastatic disease, overall survival (OS), and recurrence-free survival (RFS). Five thousand six hundred nineteen NET cases were identified. The incidence of NETs increased from 2.48 to 5.86 per 100,000 per year. Metastases were found in 20.8% at presentation and in another 38% after the initial diagnosis. The proportion of metastases at presentation decreased from 1994 to 2009 (from 29% to 13%). Therefore, although the incidence of all NETs increased, the overall incidence of metastases did not change (0.63-0.69 per 100,000 per year). The 10-year OS rate was 46.5%, and the RFS rate was 64.6%. In addition to the primary tumor site, independent predictors of worse OS included an advanced age (P incidence of NETs has markedly increased over the course of 15 years. This is the first study to provide evidence suggesting that the increase in the incidence of NETs may be due to increased detection. In addition to tumor characteristics, low income and rural residency portend worse survival for patients with NETs. © 2014 American Cancer Society.

  16. Dual fluorescent N-(2-hydroxypropyl) methacrylamide-based conjugates for passive tumor targeting with reduction-sensitive drug release: proof of the concept, tumor accumulation, and biodistribution

    Czech Academy of Sciences Publication Activity Database

    Studenovský, Martin; Heinrich, A. K.; Lucas, H.; Mueller, T.; Mäder, K.; Etrych, Tomáš

    2016-01-01

    Roč. 31, č. 4 (2016), s. 348-360 ISSN 0883-9115 R&D Projects: GA ČR(CZ) GCP207/12/J030; GA ČR(CZ) GA14-12742S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61389013 Keywords : HPMA copolymers * reduction-responsive drug release * tumor accumulation Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.310, year: 2016

  17. [A review of progress of real-time tumor tracking radiotherapy technology based on dynamic multi-leaf collimator].

    Science.gov (United States)

    Liu, Fubo; Li, Guangjun; Shen, Jiuling; Li, Ligin; Bai, Sen

    2017-02-01

    While radiation treatment to patients with tumors in thorax and abdomen is being performed, further improvement of radiation accuracy is restricted by the tumor intra-fractional motion due to respiration. Real-time tumor tracking radiation is an optimal solution to tumor intra-fractional motion. A review of the progress of real-time dynamic multi-leaf collimator(DMLC) tracking is provided in the present review, including DMLC tracking method, time lag of DMLC tracking system, and dosimetric verification.

  18. Classification between normal and tumor tissues based on the pair-wise gene expression ratio

    International Nuclear Information System (INIS)

    Yap, YeeLeng; Zhang, XueWu; Ling, MT; Wang, XiangHong; Wong, YC; Danchin, Antoine

    2004-01-01

    Precise classification of cancer types is critically important for early cancer diagnosis and treatment. Numerous efforts have been made to use gene expression profiles to improve precision of tumor classification. However, reliable cancer-related signals are generally lacking. Using recent datasets on colon and prostate cancer, a data transformation procedure from single gene expression to pair-wise gene expression ratio is proposed. Making use of the internal consistency of each expression profiling dataset this transformation improves the signal to noise ratio of the dataset and uncovers new relevant cancer-related signals (features). The efficiency in using the transformed dataset to perform normal/tumor classification was investigated using feature partitioning with informative features (gene annotation) as discriminating axes (single gene expression or pair-wise gene expression ratio). Classification results were compared to the original datasets for up to 10-feature model classifiers. 82 and 262 genes that have high correlation to tissue phenotype were selected from the colon and prostate datasets respectively. Remarkably, data transformation of the highly noisy expression data successfully led to lower the coefficient of variation (CV) for the within-class samples as well as improved the correlation with tissue phenotypes. The transformed dataset exhibited lower CV when compared to that of single gene expression. In the colon cancer set, the minimum CV decreased from 45.3% to 16.5%. In prostate cancer, comparable CV was achieved with and without transformation. This improvement in CV, coupled with the improved correlation between the pair-wise gene expression ratio and tissue phenotypes, yielded higher classification efficiency, especially with the colon dataset – from 87.1% to 93.5%. Over 90% of the top ten discriminating axes in both datasets showed significant improvement after data transformation. The high classification efficiency achieved suggested

  19. Altered self-perception in adult survivors treated for a CNS tumor in childhood or adolescence: population-based outcomes compared with the general population

    Science.gov (United States)

    Hörnquist, Lina; Rickardsson, Jenny; Lannering, Birgitta; Gustafsson, Göran; Boman, Krister K.

    2015-01-01

    Background Survivors of pediatric CNS tumors are at risk for persistent tumor/treatment-related morbidity, physical disability and social consequences that may alter self-perception, vital for self-identity, mental health and quality of survival. We studied the long-term impact of childhood CNS tumors and their treatment on the self-perception of adult survivors and compared outcomes with those of the general population. Methods The cohort included 697 Swedish survivors diagnosed with a primary CNS tumor during 1982–2001. Comparison data were randomly collected from a stratified general population sample. Survivors and general population individuals were compared as regards self-perception in 5 domains: body image, sports/physical activities, peers, work, and family, and with a global self-esteem index. Within the survivor group, determinants of impact on self-perception were identified. Results The final analyzed sample included 528 survivors, 75.8% of the entire national cohort. The control sample consisted of 995, 41% of 2500 addressed. Survivors had significantly poorer self-perception outcomes in domains of peers, work, body image, and sports/physical activities, and in the global self-perception measure, compared with those of the general population (all P type and a history of cranial radiation therapy were associated with outcomes. Conclusion An altered self-perception is a potential late effect in adult survivors of pediatric CNS tumors. Self-perception and self-esteem are significant elements of identity, mental health and quality of survival. Therefore, care and psychosocial follow-up of survivors should include measures for identifying disturbances and for assessing the need for psychosocial intervention. PMID:25332406

  20. Altered self-perception in adult survivors treated for a CNS tumor in childhood or adolescence: population-based outcomes compared with the general population.

    Science.gov (United States)

    Hörnquist, Lina; Rickardsson, Jenny; Lannering, Birgitta; Gustafsson, Göran; Boman, Krister K

    2015-05-01

    Survivors of pediatric CNS tumors are at risk for persistent tumor/treatment-related morbidity, physical disability and social consequences that may alter self-perception, vital for self-identity, mental health and quality of survival. We studied the long-term impact of childhood CNS tumors and their treatment on the self-perception of adult survivors and compared outcomes with those of the general population. The cohort included 697 Swedish survivors diagnosed with a primary CNS tumor during 1982-2001. Comparison data were randomly collected from a stratified general population sample. Survivors and general population individuals were compared as regards self-perception in 5 domains: body image, sports/physical activities, peers, work, and family, and with a global self-esteem index. Within the survivor group, determinants of impact on self-perception were identified. The final analyzed sample included 528 survivors, 75.8% of the entire national cohort. The control sample consisted of 995, 41% of 2500 addressed. Survivors had significantly poorer self-perception outcomes in domains of peers, work, body image, and sports/physical activities, and in the global self-perception measure, compared with those of the general population (all P self-perception is a potential late effect in adult survivors of pediatric CNS tumors. Self-perception and self-esteem are significant elements of identity, mental health and quality of survival. Therefore, care and psychosocial follow-up of survivors should include measures for identifying disturbances and for assessing the need for psychosocial intervention. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Sinus Tumors

    Science.gov (United States)

    ... RESOURCES Medical Societies Patient Education About this Website Font Size + - Home > CONDITIONS > Sinus Tumors Adult Sinusitis Pediatric ... and they vary greatly in location, size and type. Care for these tumors is individualized to each ...

  2. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  3. Wilms tumor

    Science.gov (United States)

    ... suggested. Alternative Names Nephroblastoma; Kidney tumor - Wilms Images Kidney anatomy Wilms tumor References Babaian KN, Delacroix SE, Wood CG, Jonasch E. Kidney cancer. In: Skorecki K, Chertow GM, Marsden PA, ...

  4. Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study

    Directory of Open Access Journals (Sweden)

    Visser Otto

    2010-06-01

    Full Text Available Abstract Background Diagnosing colorectal cancer (CRC at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear. Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC. Methods Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B and late stage (Dukes C or D cancer. Patients were followed up for 3.5 years after diagnosis. Results In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE was 31 (1.5 weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (p = 0.27. In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank p = 0.93. In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank p = 0.01. In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median versus short delay (≤median was 1.8 (95% confidence interval (CI 1.1 to 3.0; p = 0.01. Tumor-site was not associated with patient survival. When separating late stage CRC in Dukes C and Dukes D tumors, a shorter delay was associated with a shorter survival in Dukes D tumors only and not in Dukes C tumors. Conclusion In symptomatic CRC patients, a longer diagnostic and

  5. Impact of tumor cell cytoskeleton organization on invasiveness and migration: a microchannel-based approach.

    Directory of Open Access Journals (Sweden)

    Claudio G Rolli

    2010-01-01

    Full Text Available Cell migration is a fundamental feature of the interaction of cells with their surrounding. The cell's stiffness and ability to deform itself are two major characteristics that rule migration behavior especially in three-dimensional tissue. We simulate this situation making use of a micro-fabricated migration chip to test the active invasive behavior of pancreatic cancer cells (Panc-1 into narrow channels. At a channel width of 7 microm cell migration through the channels was significantly impeded due to size exclusion. A striking increase in cell invasiveness was observed once the cells were treated with the bioactive lipid sphingosylphosphorylcholine (SPC that leads to a reorganization of the cell's keratin network, an enhancement of the cell's deformability, and also an increase in the cell's migration speed on flat surfaces. The migration speed of the highly deformed cells inside the channels was three times higher than of cells on flat substrates but was not affected upon SPC treatment. Cells inside the channels migrated predominantly by smooth sliding while maintaining constant cell length. In contrast, cells on adhesion mediating narrow lines moved in a stepwise way, characterized by fluctuations in cell length. Taken together, with our migration chip we demonstrate that the dimensionality of the environment strongly affects the migration phenotype and we suggest that the spatial cytoskeletal keratin organization correlates with the tumor cell's invasive potential.

  6. Evaluation of the prognosis of cancer patients with metastatic bone tumors based on serial bone scintigrams

    International Nuclear Information System (INIS)

    Ohmori, Kazuo; Matsui, Hisao; Yasuda, Taketoshi; Kanamori, Masahiko; Yudoh, Kazuo; Seto, Hikaru; Tsuji, Haruo

    1997-01-01

    We counted the lesions at the time of detection of bone metastases and calculated the rate of increase in the number of bone metastases from changes in serial bone scintigrams, and investigated the usefulness of serial scintigrams as a prognostic indicator in patients with metastatic bone tumors. Subjects were 112 patients with bone metastases from four types of primary lesion: 21 with prostate cancer, 27 breast cancer, 39 lung cancer and 25 stomach cancer. Of these, 18 (prostate), 19 (breast), nine (lung) and eight (stomach) underwent serial bone scintigrams in which bone metastases were first detected and identified as progressing. The numbers of lesions at the time of detection of bone metastases for prostate and stomach cancers were significantly greater than those for lung cancer. The rate of increase in the number of bone metastases for stomach cancer was significantly higher than that for prostate or breast cancers. There was no correlation between the survival time after the detection of bone metastases and the number of lesions at the time of detection in the four types of cancer. However, in prostate cancer, a negative correlation existed between the survival time after the detection of bone metastases and the rate of increase in the number of bone metastases. Thus, in patients with bone metastases from prostate cancer, it appears that the rate of increase in the number of bone metastases, estimated from serial bone scintigrams, was indicative of prognosis. (author)

  7. Theoretical and practical model for implementing intensity modulated radiotherapy (IMRT) based on openness in head and neck tumors

    International Nuclear Information System (INIS)

    Napoles Morales, Misleidy; Yanes Lopez, Yaima; Ascension, Yudith; Alfonso La Guardia, Rodolfo; Calderon, Carlos

    2009-01-01

    Certain requirements have been internationally recommended for the transition from radiation therapy (3D-CRT) to intensity modulated radiation therapy (IMRT). They have been filling in clinical practice in the physical, dosimetry and quality of treatment. Prior to the implementation of IMRT have been developed preclinical will proceed according to the treatment planning techniques in the real images of patients, validating the rationale for the transition from the point of view and radiobiological dosimetry. The comparison was based on a group of patients eligible for IMRT, which were actually treated with 3D-CRT. IMRT plans were designed and applied to virtually the same patients, simulating the IMRT treatment. The prescribed dose and fractionation were similar in both techniques, to be able to compare radiobiology. The results show the rationality of IMRT in terms of reducing complications and the possibility of scaling doses in the PTV. Were used Dose Volume Histograms (HDV) obtained from the dosimetric calculations for radiobiological evaluation of treatment plans, letting through a software: 'Albireo Target' version 4.0.1.2008 calculate the equivalent uniform dose (EUD) for tumor and organs of risks (OAR) and tumor control probability (TCP) and the likelihood of damage to healthy tissue (NTCP). The results obtained with IMRT plans were more significant than with 3D-CRT especially in terms of EUD for organs at risk and NTCP. These results allow us to create the definitive basis for the implementation of IMRT in our environment. (Author)

  8. Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata.

    Science.gov (United States)

    Monteagudo, Ángel; Santos, José

    2015-01-01

    Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA) being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC) and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.

  9. Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata.

    Directory of Open Access Journals (Sweden)

    Ángel Monteagudo

    Full Text Available Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.

  10. Classification of brain tumors using texture based analysis of T1-post contrast MR scans in a preclinical model

    Science.gov (United States)

    Tang, Tien T.; Zawaski, Janice A.; Francis, Kathleen N.; Qutub, Amina A.; Gaber, M. Waleed

    2018-02-01

    Accurate diagnosis of tumor type is vital for effective treatment planning. Diagnosis relies heavily on tumor biopsies and other clinical factors. However, biopsies do not fully capture the tumor's heterogeneity due to sampling bias and are only performed if the tumor is accessible. An alternative approach is to use features derived from routine diagnostic imaging such as magnetic resonance (MR) imaging. In this study we aim to establish the use of quantitative image features to classify brain tumors and extend the use of MR images beyond tumor detection and localization. To control for interscanner, acquisition and reconstruction protocol variations, the established workflow was performed in a preclinical model. Using glioma (U87 and GL261) and medulloblastoma (Daoy) models, T1-weighted post contrast scans were acquired at different time points post-implant. The tumor regions at the center, middle, and peripheral were analyzed using in-house software to extract 32 different image features consisting of first and second order features. The extracted features were used to construct a decision tree, which could predict tumor type with 10-fold cross-validation. Results from the final classification model demonstrated that middle tumor region had the highest overall accuracy at 79%, while the AUC accuracy was over 90% for GL261 and U87 tumors. Our analysis further identified image features that were unique to certain tumor region, although GL261 tumors were more homogenous with no significant differences between the central and peripheral tumor regions. In conclusion our study shows that texture features derived from MR scans can be used to classify tumor type with high success rates. Furthermore, the algorithm we have developed can be implemented with any imaging datasets and may be applicable to multiple tumor types to determine diagnosis.

  11. Analysis of DCE-MRI features in tumor and the surrounding stroma for prediction of Ki-67 proliferation status in breast cancer

    Science.gov (United States)

    Li, Hui; Fan, Ming; Zhang, Peng; Li, Yuanzhe; Cheng, Hu; Zhang, Juan; Shao, Guoliang; Li, Lihua

    2018-03-01

    Breast cancer, with its high heterogeneity, is the most common malignancies in women. In addition to the entire tumor itself, tumor microenvironment could also play a fundamental role on the occurrence and development of tumors. The aim of this study is to investigate the role of heterogeneity within a tumor and the surrounding stromal tissue in predicting the Ki-67 proliferation status of oestrogen receptor (ER)-positive breast cancer patients. To this end, we collected 62 patients imaged with preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for analysis. The tumor and the peritumoral stromal tissue were segmented into 8 shells with 5 mm width outside of tumor. The mean enhancement rate in the stromal shells showed a decreasing order if their distances to the tumor increase. Statistical and texture features were extracted from the tumor and the surrounding stromal bands, and multivariate logistic regression classifiers were trained and tested based on these features. An area under the receiver operating characteristic curve (AUC) were calculated to evaluate performance of the classifiers. Furthermore, the statistical model using features extracted from boundary shell next to the tumor produced AUC of 0.796+/-0.076, which is better than that using features from the other subregions. Furthermore, the prediction model using 7 features from the entire tumor produced an AUC value of 0.855+/-0.065. The classifier based on 9 selected features extracted from peritumoral stromal region showed an AUC value of 0.870+/-0.050. Finally, after fusion of the predictive model obtained from entire tumor and the peritumoral stromal regions, the classifier performance was significantly improved with AUC of 0.920. The results indicated that heterogeneity in tumor boundary and peritumoral stromal region could be valuable in predicting the indicator associated with prognosis.

  12. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  13. Brain Tumors

    Science.gov (United States)

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

  14. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. A multiplexed microfluidic system for evaluation of dynamics of immune-tumor interactions.

    Science.gov (United States)

    Moore, N; Doty, D; Zielstorff, M; Kariv, I; Moy, L Y; Gimbel, A; Chevillet, J R; Lowry, N; Santos, J; Mott, V; Kratchman, L; Lau, T; Addona, G; Chen, H; Borenstein, J T

    2018-05-25

    Recapitulation of the tumor microenvironment is critical for probing mechanisms involved in cancer, and for evaluating the tumor-killing potential of chemotherapeutic agents, targeted therapies and immunotherapies. Microfluidic devices have emerged as valuable tools for both mechanistic studies and for preclinical evaluation of therapeutic agents, due to their ability to precisely control drug concentrations and gradients of oxygen and other species in a scalable and potentially high throughput manner. Most existing in vitro microfluidic cancer models are comprised of cultured cancer cells embedded in a physiologically relevant matrix, collocated with vascular-like structures. However, the recent emergence of immune checkpoint inhibitors (ICI) as a powerful therapeutic modality against many cancers has created a need for preclinical in vitro models that accommodate interactions between tumors and immune cells, particularly for assessment of unprocessed tumor fragments harvested directly from patient biopsies. Here we report on a microfluidic model, termed EVIDENT (ex vivo immuno-oncology dynamic environment for tumor biopsies), that accommodates up to 12 separate tumor biopsy fragments interacting with flowing tumor-infiltrating lymphocytes (TILs) in a dynamic microenvironment. Flow control is achieved with a single pump in a simple and scalable configuration, and the entire system is constructed using low-sorption materials, addressing two principal concerns with existing microfluidic cancer models. The system sustains tumor fragments for multiple days, and permits real-time, high-resolution imaging of the interaction between autologous TILs and tumor fragments, enabling mapping of TIL-mediated tumor killing and testing of various ICI treatments versus tumor response. Custom image analytic algorithms based on machine learning reported here provide automated and quantitative assessment of experimental results. Initial studies indicate that the system is capable of

  16. Fibroblastic and myofibroblastic tumors of the head and neck: Comprehensive imaging-based review with pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Hourani, Roula, E-mail: rh64@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Taslakian, Bedros, E-mail: bt05@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Shabb, Nina S., E-mail: ns04@aub.edu.lb [Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut (Lebanon); Nassar, Lara, E-mail: ln07@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Hourani, Mukbil H., E-mail: mh17@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Moukarbel, Roger, E-mail: rm17@aub.edu.lb [Department of Otolaryngology – Head and Neck Surgery, American University of Beirut Medical Center, Beirut (Lebanon); Sabri, Alain, E-mail: as71@aub.edu.lb [Department of Otolaryngology – Head and Neck Surgery, American University of Beirut Medical Center, Beirut (Lebanon); Rizk, Toni, E-mail: tonirisk@hotmail.com [Department of Neurosurgery, Hôtel-Dieu de France, Saint-Joseph University, Beirut (Lebanon)

    2015-02-15

    Highlights: • Almost all fibroblastic tumors are evaluated with non-invasive imaging. • Radiologists should be familiar with the imaging appearance of fibroblastic tumors. • Most appropriate initial examination when fibromatosis coli suspected is ultrasound. • Most common location of ossifying fibromas is the tooth-bearing regions. - Abstract: Fibroblastic and myofibroblastic tumors of the head and neck are a heterogeneous group of disorders characterized by the proliferation of fibroblasts, myofibroblasts, or both. These tumors may be further subclassified on the basis of their behavior as benign, intermediate with malignant potential, or malignant. There are different types of fibroblastic and myofibroblastic tumors that can involve the head and neck including desmoid-type fibromatosis, solitary fibrous tumor, myofibroma/myofibromatosis, nodular fasciitis, nasopharyngeal angiofibroma, fibrosarcoma, dermatofibrosarcoma protuberans, fibromatosis coli, inflammatory myofibroblastic tumor, ossifying fibroma, fibrous histiocytoma, nodular fasciitis, fibromyxoma, hyaline fibromatosis and fibrous hamartoma. Although the imaging characteristics of fibroblastic and myofibroblastic tumors of the head and neck are nonspecific, imaging plays a pivotal role in the noninvasive diagnosis and characterization of these tumors, providing information about the constitution of tumors, their extension and invasion of adjacent structures. Correlation with the clinical history may help limit the differential diagnosis and radiologists should be familiar with the imaging appearance of these tumors to reach an accurate diagnosis.

  17. Fibroblastic and myofibroblastic tumors of the head and neck: Comprehensive imaging-based review with pathologic correlation

    International Nuclear Information System (INIS)

    Hourani, Roula; Taslakian, Bedros; Shabb, Nina S.; Nassar, Lara; Hourani, Mukbil H.; Moukarbel, Roger; Sabri, Alain; Rizk, Toni

    2015-01-01

    Highlights: • Almost all fibroblastic tumors are evaluated with non-invasive imaging. • Radiologists should be familiar with the imaging appearance of fibroblastic tumors. • Most appropriate initial examination when fibromatosis coli suspected is ultrasound. • Most common location of ossifying fibromas is the tooth-bearing regions. - Abstract: Fibroblastic and myofibroblastic tumors of the head and neck are a heterogeneous group of disorders characterized by the proliferation of fibroblasts, myofibroblasts, or both. These tumors may be further subclassified on the basis of their behavior as benign, intermediate with malignant potential, or malignant. There are different types of fibroblastic and myofibroblastic tumors that can involve the head and neck including desmoid-type fibromatosis, solitary fibrous tumor, myofibroma/myofibromatosis, nodular fasciitis, nasopharyngeal angiofibroma, fibrosarcoma, dermatofibrosarcoma protuberans, fibromatosis coli, inflammatory myofibroblastic tumor, ossifying fibroma, fibrous histiocytoma, nodular fasciitis, fibromyxoma, hyaline fibromatosis and fibrous hamartoma. Although the imaging characteristics of fibroblastic and myofibroblastic tumors of the head and neck are nonspecific, imaging plays a pivotal role in the noninvasive diagnosis and characterization of these tumors, providing information about the constitution of tumors, their extension and invasion of adjacent structures. Correlation with the clinical history may help limit the differential diagnosis and radiologists should be familiar with the imaging appearance of these tumors to reach an accurate diagnosis

  18. Wide-field lifetime-based FRET imaging for the assessment of early functional distribution of transferrin-based delivery in breast tumor-bearing small animals

    Science.gov (United States)

    Sinsuebphon, Nattawut; Rudkouskaya, Alena; Barroso, Margarida; Intes, Xavier

    2016-02-01

    Targeted drug delivery is a critical aspect of successful cancer therapy. Assessment of dynamic distribution of the drug provides relative concentration and bioavailability at the target tissue. The most common approach of the assessment is intensity-based imaging, which only provides information about anatomical distribution. Observation of biomolecular interactions can be performed using Förster resonance energy transfer (FRET). Thus, FRET-based imaging can assess functional distribution and provide potential therapeutic outcomes. In this study, we used wide-field lifetime-based FRET imaging for the study of early functional distribution of transferrin delivery in breast cancer tumor models in small animals. Transferrin is a carrier for cancer drug delivery. Its interaction with its receptor is within a few nanometers, which is suitable for FRET. Alexa Fluor® 700 and Alexa Fluor® 750 were conjugated to holo-transferrin which were then administered via tail vein injection to the mice implanted with T47D breast cancer xenografts. Images were continuously acquired for 60 minutes post-injection. The results showed that transferrin was primarily distributed to the liver, the urinary bladder, and the tumor. The cellular uptake of transferrin, which was indicated by the level of FRET, was high in the liver but very low in the urinary bladder. The results also suggested that the fluorescence intensity and FRET signals were independent. The liver showed increasing intensity and increasing FRET during the observation period, while the urinary bladder showed increasing intensity but minimal FRET. Tumors gave varied results corresponding to their FRET progression. These results were relevant to the biomolecular events that occurred in the animals.

  19. Electrophysiological Monitoring in Patients With Tumors of the Skull Base Treated by Carbon-12 Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Carozzo, Simone [Department of Neuroscience, Ophthalmology, and Genetics, University of Genova, Genova (Italy); Schardt, Dieter [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt (Germany); Narici, Livio [Department of Physics, University of Rome Tor Vergata, Rome (Italy); Combs, Stephanie E.; Debus, Jürgen [Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany); Sannita, Walter G., E-mail: wgs@dism.unige.it [Department of Neuroscience, Ophthalmology, and Genetics, University of Genova, Genova (Italy); Department of Psychiatry, State University of New York, Stony Brook, New York (United States)

    2013-03-15

    Purpose: To report the results of short-term electrophysiologic monitoring of patients undergoing {sup 12}C therapy for the treatment of skull chordomas and chondrosarcomas unsuitable for radical surgery. Methods and Materials: Conventional electroencephalogram (EEG) and retinal and cortical electrophysiologic responses to contrast stimuli were recorded from 30 patients undergoing carbon ion radiation therapy, within a few hours before the first treatment and after completion of therapy. Methodologies and procedures were compliant with the guidelines of the International Federation for Clinical Neurophysiology and International Society for Clinical Electrophysiology of Vision. Results: At baseline, clinical signs were reported in 56.6% of subjects. Electrophysiologic test results were abnormal in 76.7% (EEG), 78.6% (cortical evoked potentials), and 92.8% (electroretinogram) of cases, without correlation with neurologic signs, tumor location, or therapy plan. Results on EEG, but not electroretinograms and cortical responses, were more often abnormal in patients with reported clinical signs. Abnormal EEG results and retinal/cortical responses improved after therapy in 40% (EEG), 62.5% (cortical potentials), and 70% (electroretinogram) of cases. Results on EEG worsened after therapy in one-third of patients whose recordings were normal at baseline. Conclusions: The percentages of subjects whose EEG results improved or worsened after therapy and the improvement of retinal/cortical responses in the majority of patients are indicative of a limited or negligible (and possibly transient) acute central nervous system toxicity of carbon ion therapy, with a significant beneficial effect on the visual pathways. Research on large samples would validate electrophysiologic procedures as a possible independent test for central nervous system toxicity and allow investigation of the correlation with clinical signs; repeated testing over time after therapy would demonstrate, and may

  20. Denosumab treatment for progressive skull base giant cell tumor of bone in a 14 year old female - a case report and literature review.

    Science.gov (United States)

    Bardakhchyan, Samvel; Kager, Leo; Danielyan, Samvel; Avagyan, Armen; Karamyan, Nerses; Vardevanyan, Hovhannes; Mkhitaryan, Sergey; Papyan, Ruzanna; Zohrabyan, Davit; Safaryan, Liana; Sargsyan, Lilit; Harutyunyan, Lilit; Hakobyan, Lusine; Iskanyan, Samvel; Tamamyan, Gevorg

    2017-03-29

    Giant cell tumor of bone (GCT) is a rare primary bone tumor, which can metastasize and undergo malignant transformation. The standard treatment of GCT is surgery. In patients with unresectable or metastatic disease, additional therapeutic options are available. These include blocking of the receptor activator of NF-kappa B ligand (RANKL) signaling pathway, which plays a role in the pathogenesis of GCT of bone, via the anti-RANKL monoclonal antibody denosumab. Herein we report on a female teenager who presented in a very poor clinical condition (cachexia, diplopia, strabismus, dysphonia with palsy of cranial nerves V, VI, VIII, IX, X, XI and XII) due to progressive disease, after incomplete resection and adjuvant radiotherapy, of a GCT which affected the cervical spine (C1 and C2) as well as the skull base; and who had an impressive clinical response to denosumab therapy. To the best of our knowledge, this is the youngest patient ever reported with a skull base tumor treated with denosumab. In situations when surgery can be postponed and local aggressiveness of the tumor does not urge for acute surgical intervention, upfront use of denosumab in order to reduce the tumor size might be considered. Principally, the goal of denosumab therapy is to reduce tumor size as much as possible, with the ultimate goal to make local surgery (or as in our case re-surgery) amenable. However, improvement in quality of life, as demonstrated in our patient, is also an important aspect of such targeted therapies.

  1. Tumor-associated antigens identified by mRNA expression profiling induce protective anti-tumor immunity

    DEFF Research Database (Denmark)

    Mathiassen, S; Lauemøller, S L; Ruhwald, M

    2001-01-01

    Defined tumor-associated antigens (TAA) are attractive targets for anti-tumor immunotherapy. Here, we describe a novel genome-wide approach to identify multiple TAA from any given tumor. A panel of transplantable thymomas was established from an inbred p53-/- mouse strain. The resulting tumors were...... of autoimmune reactions were observed. Thus, it appears possible to evaluate the entire metabolism of any given tumor and use this information rationally to identify multiple epitopes of value in the generation of tumor-specific immunotherapy. We expect that human tumors express similar tumor-specific metabolic...

  2. Succinate Dehydrogenase Subunit B (SDHB Is Expressed in Neurofibromatosis 1-Associated Gastrointestinal Stromal Tumors (Gists: Implications for the SDHB Expression Based Classification of Gists

    Directory of Open Access Journals (Sweden)

    Jeanny H. Wang, Jerzy Lasota, Markku Miettinen

    2011-01-01

    Full Text Available Gastrointestinal Stromal Tumor (GIST is the most common mesenchymal tumor of the digestive tract. GISTs develop with relatively high incidence in patients with Neurofibromatosis-1 syndrome (NF1. Mutational activation of KIT or PDGFRA is believed to be a driving force in the pathogenesis of familial and sporadic GISTs. Unlike those tumors, NF1-associated GISTs do not have KIT or PGDFRA mutations. Similarly, no mutational activation of KIT or PDGFRA has been identified in pediatric GISTs and in GISTs associated with Carney Triad and Carney-Stratakis Syndrome. KIT and PDGFRA-wild type tumors are expected to have lesser response to imatinib treatment. Recently, Carney Triad and Carney-Stratakis Syndrome -associated GISTs and pediatric GISTs have been shown to have a loss of expression of succinate dehydrogenase subunit B (SDHB, a Krebs cycle/electron transport chain interface protein. It was proposed that GISTs can be divided into SDHB- positive (type 1, and SDHB-negative (type 2 tumors because of similarities in clinical features and response to imatinib treatment. In this study, SDHB expression was examined immunohistochemically in 22 well-characterized NF1-associated GISTs. All analyzed tumors expressed SDHB. Based on SDHB-expression status, NF1-associated GISTs belong to type 1 category; however, similarly to SDHB type 2 tumors, they do not respond well to imatinib treatment. Therefore, a simple categorization of GISTs into SDHB-positive and-negative seems to be incomplete. A classification based on both SDHB expression status and KIT and PDGFRA mutation status characterize GISTs more accurately and allow subdivision of SDHB-positive tumors into different clinico-genetic categories.

  3. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  4. SU-E-I-83: Error Analysis of Multi-Modality Image-Based Volumes of Rodent Solid Tumors Using a Preclinical Multi-Modality QA Phantom

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y [University of Kansas Hospital, Kansas City, KS (United States); Fullerton, G; Goins, B [University of Texas Health Science Center at San Antonio, San Antonio, TX (United States)

    2015-06-15

    Purpose: In our previous study a preclinical multi-modality quality assurance (QA) phantom that contains five tumor-simulating test objects with 2, 4, 7, 10 and 14 mm diameters was developed for accurate tumor size measurement by researchers during cancer drug development and testing. This study analyzed the errors during tumor volume measurement from preclinical magnetic resonance (MR), micro-computed tomography (micro- CT) and ultrasound (US) images acquired in a rodent tumor model using the preclinical multi-modality QA phantom. Methods: Using preclinical 7-Tesla MR, US and micro-CT scanners, images were acquired of subcutaneous SCC4 tumor xenografts in nude rats (3–4 rats per group; 5 groups) along with the QA phantom using the same imaging protocols. After tumors were excised, in-air micro-CT imaging was performed to determine reference tumor volume. Volumes measured for the rat tumors and phantom test objects were calculated using formula V = (π/6)*a*b*c where a, b and c are the maximum diameters in three perpendicular dimensions determined by the three imaging modalities. Then linear regression analysis was performed to compare image-based tumor volumes with the reference tumor volume and known test object volume for the rats and the phantom respectively. Results: The slopes of regression lines for in-vivo tumor volumes measured by three imaging modalities were 1.021, 1.101 and 0.862 for MRI, micro-CT and US respectively. For phantom, the slopes were 0.9485, 0.9971 and 0.9734 for MRI, micro-CT and US respectively. Conclusion: For both animal and phantom studies, random and systematic errors were observed. Random errors were observer-dependent and systematic errors were mainly due to selected imaging protocols and/or measurement method. In the animal study, there were additional systematic errors attributed to ellipsoidal assumption for tumor shape. The systematic errors measured using the QA phantom need to be taken into account to reduce measurement

  5. Histological type and grade of breast cancer tumors by parity, age at birth, and time since birth: a register-based study in Norway

    Directory of Open Access Journals (Sweden)

    Heuch Ivar

    2010-05-01

    Full Text Available Abstract Background Some studies have indicated that reproductive factors affect the risk of histological types of breast cancer differently. The long-term protective effect of a childbirth is preceded by a short-term adverse effect. Few studies have examined whether tumors diagnosed shortly after birth have specific histological characteristics. Methods In the present register-based study, comprising information for 22,867 Norwegian breast cancer cases (20-74 years, we examined whether histological type (9 categories and grade of tumor (2 combined categories differed by parity or age at first birth. Associations with time since birth were evaluated among 9709 women diagnosed before age 50 years. Chi-square tests were applied for comparing proportions, whereas odds ratios (each histological type vs. ductal, or grade 3-4 vs. grade 1-2 were estimated in polytomous and binary logistic regression analyses. Results Ductal tumors, the most common histological type, accounted for 81.4% of all cases, followed by lobular tumors (6.3% and unspecified carcinomas (5.5%. Other subtypes accounted for 0.4%-1.5% of the cases each. For all histological types, the proportions differed significantly by age at diagnoses. The proportion of mucinous and tubular tumors decreased with increasing parity, whereas Paget disease and medullary tumors were most common in women of high parity. An increasing trend with increasing age at first birth was most pronounced for lobular tumors and unspecified carcinomas; an association in the opposite direction was seen in relation to medullary and tubular tumors. In age-adjusted analyses, only the proportions of unspecified carcinomas and lobular tumors decreased significantly with increasing time since first and last birth. However, ductal tumors, and malignant sarcomas, mainly phyllodes tumors, seemed to occur at higher frequency in women diagnosed Conclusion Our results support previous observations that reproductive factors

  6. Psychological consideration in patients with cerebral gliomas candidates for intra-operative radiation therapy based on tumor location.

    Science.gov (United States)

    Seddighi, Afsoun; Akbari, Mohammad Esmaeil; Seddighi, Amir Saied; Nikouei, Amir

    2017-01-01

    Intra-operative Radiation Therapy (IORT) is gaining popularity as an adjuvant option to surgical resection, in treatment of glioblastoma multiforme (GBM) for increasing survival rate, which a highly aggressive cerebral tumor with poor prognosis. Τhe authors plan to investigate the effects of IORT combined with surgical resection on the psychological status of these patients based on tumor location. From December 2013 to February 2017, we have enrolled 109 patients with high grade cerebral gliomas, documented by Magnetic Resonance Spectroscopy (MRS). Patients with previous history of brain surgery or radiation, altered mental status and psychological content and patients diagnosed with metastases were excluded. Demographic data, tumor volume based on pre-operative Magnetic Resonance Imaging (MRI) and psychological status were recorded based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The remaining 56 patients, were equally randomized into conventional (surgical resection-group A), and trial (surgical resection with IORT-group B) who underwent IORT using the 50kV INTRABEAM® system (Carl Zeiss Meditec AG, Germany). Psychological profiles of both groups were re-evaluated in the 3 rd post-operative month. Group A consisted of 18 males and 10 females with mean age of 54.4 years, while group B consisted of 16 males and 12 females with mean age of 57.8 years. Tumor volumetry revealed mean 81.52cc and 82.8cc for group A and B respectively. (P value 0.14) Patients were classified based on glioma location on pre-operative MRI: a) left parietal lobe (6 in group A, 5 in group B); b) left temporal lobe (7 in group A, 5 in group B); c) right parietal lobe (5 in group A, 6 in group B); d) left fronto-temporal lobe (4 in group A, 6 in group B); e) left parieto-temporal lobe (4 in group A, 5 in group B); and, f) right frontal lobe (2 in group A, 1 in group B). Group B received mean 8.05 Gy radiation for mean 11.2 minutes. Post

  7. Assessment of tumor blood flow and its correlation with histopathologic features in skull base meningiomas and schwannomas by using pseudo-continuous arterial spin labeling images

    International Nuclear Information System (INIS)

    Yamamoto, Tatsuya; Takeuchi, Hiroaki; Kinoshita, Kazuyuki; Kosaka, Nobuyuki; Kimura, Hirohiko

    2014-01-01

    Objective: We aimed to investigate whether pseudo-continuous arterial spin labeling (pcASL)-MRI can adequately evaluate tumor perfusion even if the tumors are located in the skull base region and evaluate the correlation between tumor blood flow (TBF) and the histopathologic features of skull base meningiomas and schwannomas. Materials and methods: We enrolled 31 patients with skull base meningioma (n = 14) and schwannoma (n = 17) who underwent surgical resection. TBF was calculated from pcASL. Tissue sections were stained with CD34 to evaluate microvessel area (MVA). TBF and MVA ratio were compared between meningiomas and schwannomas using Mann–Whitney U-test. The correlations between MVA ratio and TBF were evaluated in each tumor by using single linear regression analysis and Spearman's rank correlation coefficients (r s ). Results: MVA ratio and TBF were significantly higher in meningioma than in schwannoma (both p < 0.01). Correlation analyses revealed significant positive correlations between MVA ratio and both mean and max TBF for meningiomas (r s = 0.89, 0.81, both p < 0.01). There was a weak positive correlation between MVA ratio and mean TBF for schwannomas (r s = 0.43, p = 0.04). However, no significant correlation was found between MVA ratio and max TBF for schwannoma. Conclusions: pcASL-MRI is useful for evaluating tumor perfusion even if the tumors are located in the skull base region. Moreover, pcASL-TBF was significantly higher in most meningiomas compared to schwannomas, which can help in the differential diagnosis of the 2 tumor types even without the use of contrast material

  8. Healthcare resource use, comorbidity, treatment and clinical outcomes for patients with primary intracranial tumors: a Swedish population-based register study.

    Science.gov (United States)

    Bergqvist, Jenny; Iderberg, Hanna; Mesterton, Johan; Bengtsson, Nils; Wettermark, Björn; Henriksson, Roger

    2017-03-01

    Primary intracranial tumors are relatively uncommon and heterogeneous, which make them challenging to study. We coupled data from unique Swedish population-based registries in order to deeper analyze the most common intracranical tumor types. Patient characteristics (e.g. comorbidities), care process measures like adherence to national guidelines, healthcare resource use and clinical outcome was evaluated. A register-based study including several population-based registries for all patients living in Stockholm-Gotland, diagnosed with primary intracranial tumor between 2001 and 2013 was performed. Patient characteristics were captured and investigated in relation to survival, healthcare resource use (inpatient-, outpatient- and primary care) and treatment process. High-grade glioma and meningioma were the most common tumor types and most patients (76%) were above the age of 40 in the patient population (n = 3664). Older age, comorbidity (Elixhauser comorbidity index) and type of tumor (high-grade glioma) were associated with lower survival rate and increased use of healthcare resources, analyzed for patients living in Stockholm (n = 3031). The analyses of healthcare use and survival showed no differences between males and females, when stratifying by tumor types. Healthcare processes were not always consistent with existing national treatment recommendations for patients with high-grade gliomas (n = 474) with regard to specified lead times, analyzed in the Swedish Brain Tumor Registry, as also observed at the national level. Age, comorbidity and high-grade gliomas, but not sex, were associated with decreased survival and increased use of healthcare resources. Fewer patients than aimed for in national guidelines received care according to specified lead times. The analysis of comprehensive population-based register data can be used to improve future care processes and outcomes.

  9. Management of CNS tumors

    International Nuclear Information System (INIS)

    Griem, M.L.

    1987-01-01

    The treatment of tumors of the CNS has undergone a number of changes based on the impact of CT. The use of intraoperative US for the establishment of tumor location and tumor histology is demonstrated. MR imaging also is beginning to make an impact on the diagnosis and treatment of tumors of the CNS. Examples of MR images are shown. The authors then discuss the important aspects of tumor histology as it affects management and newer concepts in surgery, radiation, and chemotherapy on tumor treatment. The role of intraoperative placement of radioactive sources, the utilization of heavy particle radiation therapy, and the potential role of other experimental radiation therapy techniques are discussed. The role of hyperfractionated radiation and of neutrons and x-ray in a mixed-beam treatment are discussed in perspective with standard radiation therapy. Current chemotherapy techniques, including intraarterial chemotherapy, are discussed. The complications of radiation therapy alone and in combination with chemotherapy in the management of primary brain tumors, brain metastases, and leukemia are reviewed. A summary of the current management of pituitary tumors, including secreting pituitary adenomas and chromophobe adenomas, are discussed. The treatment with heavy particle radiation, transsphenoidal microsurgical removal, and combined radiotherapeutic and surgical management are considered. Tumor metastasis management of lesions of the brain and spinal cord are considered

  10. Occupational Health Impacts Due to Exposure to Organic Chemicals over an Entire Product Life Cycle.

    Science.gov (United States)

    Kijko, Gaël; Jolliet, Olivier; Margni, Manuele

    2016-12-06

    This article presents an innovative approach to include occupational exposures to organic chemicals in life cycle impact assessment (LCIA) by building on the characterization factors set out in Kijko et al. (2015) to calculate the potential impact of occupational exposure over the entire supply chain of product or service. Based on an economic input-output model and labor and economic data, the total impacts per dollar of production are provided for 430 commodity categories and range from 0.025 to 6.6 disability-adjusted life years (DALY) per million dollar of final economic demand. The approach is applied on a case study assessing human health impacts over the life cycle of a piece of office furniture. It illustrates how to combine monitoring data collected at the manufacturing facility and averaged sector specific data to model the entire supply chain. This paper makes the inclusion of occupational exposure to chemicals fully compatible with the LCA framework by including the supply chain of a given production process and will help industries focus on the leading causes of human health impacts and prevent impact shifting.

  11. Entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos

    International Nuclear Information System (INIS)

    Kao, K.R.; Elinson, R.P.

    1988-01-01

    The body plan of Xenopus laevis can be respecified by briefly exposing early cleavage stage embryos to lithium. Such embryos develop exaggerated dorsoanterior structures such as a radial eye and cement gland. In this paper, we demonstrate that the enhanced dorsoanterior phenotype results from an overcommitment of mesoderm to dorsoanterior mesoderm. Histological and immunohistochemical observations reveal that the embryos have a greatly enlarged notochord with very little muscle tissue. In addition, they develop a radial, beating heart, suggesting that lithium also specifies anterior mesoderm and pharyngeal endoderm. Randomly oriented diametrically opposed marginal zone grafts from lithium-treated embryos, when transplanted into ultraviolet (uv)-irradiated axis-deficient hosts, rescue dorsal axial structures. These transplantation experiments demonstrate that the entire marginal zone of the early gastrula consists of presumptive dorsal mesoderm. Vital dye marking experiments also indicate that the entire marginal zone maps to the prominent proboscis that is composed of chordamesoderm and represents the long axis of the embryo. These results suggest that lithium respecifies the mesoderm of Xenopus laevis embryos so that it differentiates into the Spemann organizer. We suggest that the origin of the dorsoanterior enhanced phenotypes generated by lithium and the dorsoanterior deficient phenotypes generated by uv irradiation are due to relative quantities of organizer. Our evidence demonstrates the existence of a continuum of body plan phenotypes based on this premise

  12. Investigation of in vivo PIXE effect within superficial tumor model of high-Z metalnanoplatform for PIXE-based proton therapy

    International Nuclear Information System (INIS)

    Kim, Jong Ki; Seo, Seung Jun; Lee, Ju Hong

    2010-04-01

    Metallic nanoparticles (MNP) are able to release localized X-ray when activated with high energy proton beam by particle induced X-ray emissions (PIXE) effect. The exploitation of this phenomenon in the therapeutic irradiation of tumors has been investigated. PIXE-based X-ray emission directed at CT-26 tumor cells in vitro, when administered with either gold (average diameter, 2 nm and 13 nm) or iron (average diameter, 14 nm) nanoparticles, increased with MNP solution concentration over the range of 0.1-2 mg/mL. With irradiation by 45-MeV proton therapy (PT) beam, higher concentrations had a decreased cell survival fraction. An in vivo study with tumor regression assay demonstrated significant tumor dose enhancement, thought to be result of the PIXE effect when compared to conventional PT without MNP using a 45 MeV proton beam (p<0.01). These effects were observed for gold and iron MNP, injected in doses of 100-300mg/kg body weight into CT-26 mouse tumor models via tail vein. A therapeutic effective MNP concentration range, in vivo,was estimated at 30-79 μg/g tissue for both gold and iron nanoparticles. The tumor dose enhancement may compensate for an increase in entrance dose associated with conventional PT when treating large, solid tumors with a spread out Bragg peak (SOBP) technique. The use of combined high energy Bragg peak PT with PIXE generated by MNP, or PIXE alone may result in new treatment options for infiltrative metastatic tumors and other diffuse inflammatory diseases

  13. A phase I/II study on stereotactic body radiotherapy with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm for lung tumors.

    Science.gov (United States)

    Iwata, Hiromitsu; Ishikura, Satoshi; Murai, Taro; Iwabuchi, Michio; Inoue, Mitsuhiro; Tatewaki, Koshi; Ohta, Seiji; Yokota, Naoki; Shibamoto, Yuta

    2017-08-01

    In this phase I/II study, we assessed the safety and initial efficacy of stereotactic body radiotherapy (SBRT) for lung tumors with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm. Study subjects had histologically confirmed primary non-small-cell lung cancer staged as T1a-T2aN0M0 and pulmonary oligometastasis. The primary endpoint was the incidence of Grade ≥3 radiation pneumonitis (RP) within 180 days of the start of SBRT. The secondary endpoint was local control and overall survival rates. Five patients were initially enrolled at level 1 [50 Gy/4 fractions (Fr)]; during the observation period, level 0 (45 Gy/4 Fr) was opened. The dose was escalated to the next level when grade ≥3 RP was observed in 0 out of 5 or 1 out of 10 patients. Virtual quality assurance planning was performed for 60 Gy/4 Fr; however, dose constraints for the organs at risk did not appear to be within acceptable ranges. Therefore, level 2 (55 Gy/4 Fr) was regarded as the upper limit. After the recommended dose (RD) was established, 15 additional patients were enrolled at the RD. The prescribed dose was normalized at the 95% volume border of the planning target volume based on the Monte Carlo algorithm. Between September 2011 and September 2015, 40 patients (primary 30; metastasis 10) were enrolled. Five patients were enrolled at level 0, 15 at level 1, and 20 at level 2. Only one grade 3 RP was observed at level 1. Two-year local control and overall survival rates were 98 and 81%, respectively. The RD was 55 Gy/4 Fr. SBRT with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm was tolerated well and appeared to be effective for solitary lung tumors.

  14. Magnetic resonance imaging-based detection of glial brain tumors in mice after antiangiogenic treatment.

    NARCIS (Netherlands)

    Claes, A.; Gambarota, G.; Hamans, B.C.; Tellingen, O. van; Wesseling, P.; Maass, C.N.; Heerschap, A.; Leenders, W.P.J.

    2008-01-01

    Proper delineation of gliomas using contrast-enhanced magnetic resonance imaging (CE-MRI) poses a problem in neuro-oncology. The blood brain barrier (BBB) in areas of diffuse-infiltrative growth may be intact, precluding extravasation and subsequent MR-based detection of the contrast agent

  15. Evaluation of diffusion-tensor imaging-based global search and tractography for