Relevant bibliographies by topics / Molecular radiotherapy

Contents

  1. Journal articles
  2. Dissertations / Theses
  3. Books
  4. Book chapters
  5. Conference papers
  6. Reports

Academic literature on the topic 'Molecular radiotherapy'

Author: Grafiati
Published: 4 June 2021
Last updated: 7 July 2024

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Journal articles on the topic "Molecular radiotherapy"

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Buscombe, John, and Shaunak Navalkissoor. "Molecular radiotherapy." Clinical Medicine 12, no. 4 (August 2012): 381–86. http://dx.doi.org/10.7861/clinmedicine.12-4-381.

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Buscombe, JohnR. "Clinical Trials and Molecular Radiotherapy." World Journal of Nuclear Medicine 14, no. 2 (2015): 73. http://dx.doi.org/10.4103/1450-1147.154227.

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D’Arienzo, Marco, Marco Capogni, Vere Smyth, Maurice Cox, Lena Johansson, Jaroslav Solc, Christophe Bobin, Hans Rabus, and Leila Joulaeizadeh. "Metrological Issues in Molecular Radiotherapy." EPJ Web of Conferences 77 (2014): 00022. http://dx.doi.org/10.1051/epjconf/20147700022.

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Gaze, M. N., and G. D. Flux. "Molecular radiotherapy — the radionuclide raffle?" British Journal of Radiology 83, no. 996 (December 2010): 995–97. http://dx.doi.org/10.1259/bjr/32706189.

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Glatting, Gerhard, Manuel Bardiès, and Michael Lassmann. "Treatment planning in molecular radiotherapy." Zeitschrift für Medizinische Physik 23, no. 4 (December 2013): 262–69. http://dx.doi.org/10.1016/j.zemedi.2013.03.005.

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Price, Pat. "Molecular imaging to improve radiotherapy." Radiotherapy and Oncology 78, no. 3 (March 2006): 233–35. http://dx.doi.org/10.1016/j.radonc.2006.01.004.

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Marples, B., O. Greco, M. C. Joiner, and S. D. Scott. "Molecular approaches to chemo-radiotherapy." European Journal of Cancer 38, no. 2 (January 2002): 231–39. http://dx.doi.org/10.1016/s0959-8049(01)00367-7.

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Wadsley, J., and G. Flux. "Molecular Radiotherapy Comes of Age." Clinical Oncology 33, no. 2 (February 2021): 65–67. http://dx.doi.org/10.1016/j.clon.2020.12.004.

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Chorna, Inna. "MOLECULAR MECHANISMS UNDERLYING CANCER CELL RADIORESISTANCE." Scientific Journal of Polonia University 48, no. 5 (January 17, 2022): 142–51. http://dx.doi.org/10.23856/4818.

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Radioresistance of the tumor cells remains a significant obstacle for the radiotherapy treatment of cancer. Radioresistance involves multiple genes, factors, and mechanisms that adapt cancer cells or tissues to radiotherapy-induced changes and develop resistance to ionizing radiation. The major studies of the effect of radiation on cells reported include the following areas: 1) the study of DNA damages and their repair; 2) mutations in tumor suppressor genes and radiation-induced oncogene expression; 3) the role of growth factors and cytokines; 4) violation of the cell cycle; 5) elucidation of the mechanisms of apoptosis and necrosis. This review aimed to provide a theoretical basis, which may improve the sensitivity of cancer cells to radiotherapy. It focuses on the roles of tumor metabolism, DNA repair capacity, cell cycle checkpoints, and the tumor microenvironment in the development of radioresistance of cancer cells. Understanding the molecular alterations that lead to radioresistance may provide new diagnostic markers and therapeutic targets to improve radiotherapy efficacy.
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Murray, Iain, and Glenn Flux. "Applying radiobiology to clinical molecular radiotherapy." Nuclear Medicine and Biology 100-101 (September 2021): 1–3. http://dx.doi.org/10.1016/j.nucmedbio.2021.05.005.

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Dissertations / Theses on the topic "Molecular radiotherapy"

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Evert, Jasmine. "Molecular studies of radiotherapy and chemotherapy in colorectal cancer." Doctoral thesis, Örebro universitet, Institutionen för hälsovetenskap och medicin, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-43635.

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Power, Olive Mary. "Cellular and molecular mechanisms affecting tumour radiosensitivity : an in vitro study." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286344.

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Obeidat, Mohammad Ali. "Radiotherapy Measurements with a Deoxyribonucleic Acid Doublestrand-Break Dosimeter." Thesis, The University of Texas Health Science Center at San Antonio, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10281552.

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Many types of dosimeters are used in the clinic to measure radiation dose for therapy but none of them directly measures the biological effect of this dose. The overall purpose of this work was to develop a dosimeter that measures biological damage in the form of double-strand breaks to deoxyribonucleic acid. This dosimeter could provide a more biologically relevant measure of radiation damage than the currently utilized dosimeters. A pair of oligonucleotides was designed to fabricate this dosimeter. One is labeled with a 5’-end biotin and the other with a 5’-end 6 Fluorescein amidite (fluorescent dye excited at 495?nanometer, with a peak emission at 520 nanometer). These were designed to adhere to certain locations on the pRS316 vector and serve as the primers for polymerase chain reactions. The end product of this reaction is a 4 kilo-base pair double strands deoxyribonucleic acid fragment with biotin on one end and 6 Fluorescein amidite oligonucleotide on the other attached to streptavidin beads. The biotin end connects the double strands deoxyribonucleic acid to the streptavidin bead. These bead-connected double strands deoxyribonucleic acid were suspended in 50 microliter of phosphate-buffered saline and placed into a tube for irradiation. Following irradiation of the deoxyribonucleic acid dosimeter, we take advantage of the magnetic properties of the streptavidin bead by placing our sample microtube against a magnet. The magnetic field pulls the streptavidin beads against the side of the tube. If a double-strand-break has occurred for a double strands deoxyribonucleic acid, the fluorescein end of the double strands deoxyribonucleic acid becomes free and is no longer attached to the bead or held against the side of the microtube. The free fluorescein following a double-strand-break in double strands deoxyribonucleic acid is referred to here as supernatant. The supernatant is extracted and placed in another microtube, while the unbroken double strands deoxyribonucleic acid remain attached to the beads and stay in the microtube (Fig. 4). Those beads were re-suspended with 50 microliter of phosphate-buffered saline again (called beads), then we placed both supernatant and beads in a reader microplate and we read the fluorescence signal for both with a fluorescence reader (BioTek Synergy 2). These beads and supernatant fluorescence signals are denoted by B and S, respectively. The relative amount of supernatant fluorescence counts is proportional to the probability of a double-strand-break. The probability of double-strand-break was calculated with the following equation:

(S-BG)/(S+B-2BG) (1)

where S was the supernatant fluorescence intensity (related to the number of double strands deoxyribonucleic acid with double-strand breaks), B was the re-suspended beads fluorescence intensity (related to the number of double strands deoxyribonucleic acid without double-strand breaks), and BG was the phosphate-buffered saline fluorescence intensity (related to the background signal). There are two advantages that this type of dosimeter has over the gel separation technique. First, it is important to irradiate deoxyribonucleic acid in a solution that has similar osmolarity and ion concentrations to that in a human, such as phosphate-buffered saline. A gel dosimeter would require a transfer to gel to separate deoxyribonucleic acid, whereas our dosimeter can be separated in this solution. Currently, we use pipettes to manually perform this separation, but this step could be automated. Second, the magnetic deoxyribonucleic acid separation technique is much faster than that for gel electrophoresis. Calibration of radiotherapy equipment isn’t something that happens in national science laboratories, with only world-leading experts. This is something that happens locally at every cancer clinic, with physicists that do not have the luxury of focusing solely on this one measurement. For this reason, ease of use is critical for this type of technology. (Abstract shortened by ProQuest.)

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Watchman, Christopher J. "Skeletal dosimetry models for alpha-particles for use in molecular radiotherapy." [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0012165.

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Sirzén, Florin. "Molecular aspects of cellular radiosensitivity in small cell lung carcinoma /." Stockholm, 1998. http://diss.kib.ki.se/1998/19981204sirz/.

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Finocchiaro, Domenico <1993&gt. "Applications of metrological techniques for clinical implementation of dosimetry and radiobiology in molecular radiotherapy." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amsdottorato.unibo.it/9250/3/PhD_Thesis_Finocchiaro.pdf.

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Molecular radiotherapy (MRT) is a fast developing and promising treatment for metastasised neuroendocrine tumours. Efficacy of MRT is based on the capability to selectively "deliver" radiation to tumour cells, minimizing administered dose to normal tissues. Outcome of MRT depends on the individual patient characteristics. For that reason, personalized treatment planning is important to improve outcomes of therapy. Dosimetry plays a key role in this setting, as it is the main physical quantity related to radiation effects on cells. Dosimetry in MRT consists in a complex series of procedures ranging from imaging quantification to dose calculation. This doctoral thesis focused on several aspects concerning the clinical implementation of absorbed dose calculations in MRT. Accuracy of SPECT/CT quantification was assessed in order to determine the optimal reconstruction parameters. A model of PVE correction was developed in order to improve the activity quantification in small volume, such us lesions in clinical patterns. Advanced dosimetric methods were compared with the aim of defining the most accurate modality, applicable in clinical routine. Also, for the first time on a large number of clinical cases, the overall uncertainty of tumour dose calculation was assessed. As part of the MRTDosimetry project, protocols for calibration of SPECT/CT systems and implementation of dosimetry were drawn up in order to provide standard guidelines to the clinics offering MRT. To estimate the risk of experiencing radio-toxicity side effects and the chance of inducing damage on neoplastic cells is crucial for patient selection and treatment planning. In this thesis, the NTCP and TCP models were derived based on clinical data as help to clinicians to decide the pharmaceutical dosage in relation to the therapy control and the limitation of damage to healthy tissues. Moreover, a model for tumour response prediction based on Machine Learning analysis was developed.
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Shukla, Lipi. "Uncovering the cellular and molecular mechanisms of radiotherapy soft tissue injury and fat graft treatment." Phd thesis, Australian Catholic University, 2018. https://acuresearchbank.acu.edu.au/download/3366f35e7cf70efbda7b83341ffc736dd57db88f2ae4bce72a3467ad86e840b5/165644017/Shukla_2018_Uncovering_cellular_and_molecular_mechanisms_of.pdf.

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Over half of the 120,000 patients diagnosed with a solid tumour in Australia annually require radiotherapy as part of their treatment. Despite significantly enhancing cancer survival, the damage done to healthy native tissues is inevitable and problematic. Radiotherapy soft tissue injury is progressive, may intensify years after treatment and is characterised by pain, contracture, tissue breakdown, recurrent infection and lymphoedema. Important implications of radiation injury for surgeons are that surgical procedures (whether for functional restoration or cancer recurrence) in irradiated tissues become technically difficult and more hazardous. Direct wound closure or local flaps are restricted by stiff, non-compliant tissue, and even if wound edges are opposable, they are frequently subject to poor wound healing or breakdown. Further, the ability of an irradiated wound bed to accept skin grafts is diminished, necessitating more complex reconstructive procedures such as free microvascular tissue transfer from distant sites, in which radiation injury is also a chief contributing factor to poor patient outcome. First, essential cell-specific functions were investigated to establish the effects of radiotherapy-injury on the ability of the cells in skin and subcutaneous tissues to survive or respond to subsequent injury or challenge. Next, molecular alterations resulting from irradiation were characterised at mRNA level using next generation sequencing and further investigated using pathway analysis. Finally, the reparative potential of the adipose-derived stem cells (ADSCs) to reduce radiotherapy injury was investigated in using a similar panel of cellular assays. The constituent proteins secreted by these cells that exerted a regenerative effect were then isolated for further analyses. The results detailed in this thesis demonstrate that each individual component of skin and subcutaneous tissue exhibits a unique response to radiotherapy injury - challenging the traditional dogma that large scale irreversible cell death is responsible for the manifestation of radiotherapy soft tissue injury. Notable findings include radiotherapy-induced hyper-migration of fibroblasts and pericytes, reduced apoptosis in endothelial and stem cell populations, global suppression of lymphatic endothelial cell (LEC) repair functions and significant alterations in the differentiation capacity of ADSCs. Next generation gene sequencing revealed key molecular alterations resulting from radiotherapy in a variety of cell types. Significant findings include dysregulation of extracellular matrix proteins and basement membrane collagens – changes likely to contribute to the hypermigratory, adhesive and highly contractile phenotype seen in irradiated fibroblasts. Up-regulation of intercellular adhesion molecule 1 (ICAM-1) in blood vessel endothelial cells found in acute radiotherapy injury was validated in irradiated human tissues and was demonstrated to remain persistently elevated months-to-years after completion of therapy. This finding suggested a key candidate for application to mitigate radiotherapy injury at both the micro and macrovascular level. In order to combat the impaired functions seen in LECs after irradiation, experiments were conducted using stimulation with known potent lymphangiogenic factors VEGF-C and VEGF-D. Irradiated LEC demonstrated an obliterated capacity for response to this stimulation, due to a unique profile of ablated VEGF receptor (VEGFR) -2 signaling and reduced VEGFR-3 activation. Concurrently, up-regulation of interleukin (IL) -8 and chemokine receptor CXCR7 in irradiated LEC was seen and validated in mouse and human tissues to remain upregulated in chronic radiotherapy injury. These two protein candidates, not typically associated with lymphangiogenic properties demonstrated selective lymphangiogenic effect in both normal and irradiated LECs. Together this novel set of data suggest that LECs attempt to regenerate after radiotherapy injury using parallel signaling axes to the traditional VEGF-C and VEGF-D signaling pathways, which are uniquely rendered impotent by radiotherapy injury. Overall, methods to salvage irradiated tissues to a point to which soft-tissue quality would permit simple wound closure or other tissue repair techniques is desperately needed by clinicians. Fat grafting has been reported as a promising avenue to achieve this when used in previously irradiated areas. It was incidentally noted that irradiated tissue overlying the fat graft became more compliant and less lymphoedematous. The diminished capacity of irradiated ADSC to migrate and differentiate to fat represented significant impairments in their regenerative function. Radiation not only impairs loco-regional ADSC function, but was also shown to block the recruitment and homing of functional ADSC from sites distant to the injury. This may be due to the mentioned presence of CXCR7 secreted by irradiated LEC. Therefore, to overcome injury and aid in regeneration of tissues the mechanical introduction of healthy ADSC, via fat grafting may be needed to override the failed ADSC recruitment mechanisms. In the fat grafting model using the introduction of the secretome of ADSCs, ADSC-conditioned media (ADSCCM) was able to reverse the effects of radiotherapy injury in both fibroblasts and LEC populations. The final section of this thesis investigated putative therapeutic mechanisms by which ADSCs reverse radiotherapy induced soft tissue injury. Examination of ADSCCM was performed using proteomics, exosome analysis and metabolomics approaches. Several key candidates were identified that may lead to promising therapeutic avenues by which radiotherapy injury can be mitigated. Understanding of the cellular and molecular mechanisms of radiotherapy induced soft tissue injury, methods by which ADSCCM mediates reversal of the resulting cell dysfunction will provide vital clues and putative therapeutic channels by which to reverse these pathological alterations, thereby reducing the devastating burden of chronic, debilitating side effects of radiotherapy such as fibrosis, lymphoedema and other related diseases, in cancer survivors.
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Trigila, Carlotta. "Development of a portable gamma imaging system for absorbed radiation dose control in molecular radiotherapy." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS285.

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La thérapie interne par radionucléides est encore aujourd’hui un domaine peu exploité parmi les différentes modalités de traitement contre le cancer. Son spectre d’applications est toutefois en pleine évolution grâce notamment à l'apparition de nouveaux radiopharmaceutiques émetteurs beta ou alpha (peptides, alpha-thérapie ²²³ Ra, alpha-immunothérapie ²²¹ As,...) (Ersahin 2011). Dans ce contexte, la grande hétérogénéité des doses délivrées et des effets observés, à la fois en terme de toxicité et de réponse, démontrent qu'une dosimétrie personnalisée est essentielle pour optimiser le traitement (Strigari 2011). En pratique clinique, la dosimétrie de la tumeur et des organes à risque (foie, rein, ...) repose sur l’image de la biodistribution et de la cinétique précise du radiopharmaceutique chez chaque patient. Ces images peuvent être réalisées avec un traceur pré-thérapeutique pour planifier le traitement ou après celui-ci, afin de corréler directement les effets observés aux doses délivrées de manière à optimiser le protocole (activité maximum à injecter, intervalle entre les injections). Les contraintes de détection imposées par les protocoles de traitement sont très différentes de celles associées à un examen diagnostique (Flux 2011, Konijnenberg 2011). Les gamma-caméras conventionnelles ne sont ainsi pas adaptées à la détection de fortes activités de rayonnements gamma d'énergies inférieures à 100 keV (²²³ Ra) ou supérieures à 300 keV (¹³¹I, ⁹⁰Y). D’autre part, les fortes activités des traceurs injectés exigent généralement que le patient reste isolé, ce qui le rend donc plus difficilement accessible par les techniques d’imagerie standard. Enfin, la disponibilité de ces systèmes est incompatible avec un échantillonnage temporel précis de la cinétique du traceur, qui joue un rôle très important dans la quantification des doses absorbées. L'objectif de ma thèse était de proposer de nouvelles approches instrumentales visant à renforcer le contrôle de la dose délivrée aux patients lors d'un traitement de radiothérapie moléculaire. Ceci est réalisé en réduisant les incertitudes associées à la quantification de l'activité (et donc au calcul de la dose absorbée) grâce à l'utilisation d'un système d'imagerie compact et hautement optimisé. Il consistait à mettre au point et à optimiser une gamma-caméra mobile miniaturisée à haute résolution spécialement conçue pour améliorer l'évaluation quantitative individuelle de la distribution hétérogène et de la bio-cinétique du radiotraceur avant et après administration du traitement. L'étude était axée sur le traitement des maladies bénignes et malignes de la thyroïde à l'aide de l'¹³¹ I. Le premier prototype de la caméra, avec un champ de vue de 5x5 cm² , consiste en un collimateur à trous parallèles à haute énergie, réalisé en impression 3D et optimisé par simulations Monte Carlo, couplé à un scintillateur inorganique continu, lu par une technologie récente basée sur des matrices de photomultiplicateurs au silicium (SiPM). Ses propriétés intrinsèques, en termes d'énergie et de réponse spatiale, ont été testées avec des sources ponctuelles de ⁵⁷ Co et ¹³³ Ba. Le premier prototype de la caméra a été calibré avec de l'¹³¹ I. La calibration du système conduit à une résolution spatiale globale de (3.14±0.03) mm et à une sensibilité moyenne de (1.23±0.01) cps/MBq, le deux à 5 cm de distance. Nous avons effectué les premières études précliniques avec l'utilisation de différents fantômes thyroïdiens imprimés en 3D, avec et sans nodules, remplis de ¹³¹ I. Des résultats très prometteurs ont été atteints (valeurs de RC proches de l’unité), qui mettent en évidence ses performances adaptées à une quantification précise dans un contexte clinique assez réaliste
Targeted radionuclide therapy is still a developing area among the different treatment modalities against cancer. However, its range of applications is rapidly expanding thanks to the emergence of new radiopharmaceuticals labeled with beta or alpha emitters (peptides, ²²³ Ra alpha-therapy, ²²¹ As alpha- immunotherapy, ...) (Ersahin 2011). In that context, the large heterogeneity of absorbed doses and the range of effects observed, both in terms of toxicity and response, demonstrate that individualized patient dosimetry is essential to optimize this therapy (Strigari 2011). In clinical practice, patient-specific dosimetry of tumors and organs-at-risk (liver, kidney, ...) is image-based and rely on the quantification of radio- pharmaceutical uptake as a function of time. These images can be obtained from either a pre-therapy tracer study or from a previous therapy procedure. The detection constraints imposed by the treatment protocols are very different from those associated with diagnostic imaging. (Flux 2011 Konijnenberg 2011). Thus, conventional gamma cameras are not suited for detecting high activity of gamma emitters with energy below 100 keV (²²³ Ra) or greater than 300 keV (¹³¹ I, ⁹⁰Y ). Moreover, high activities of the injected tracer typically require isolation of the patient, making the use of standard imaging devices difficult. Finally, the availability of these devices is incompatible with an accurate temporal sampling of the kinetics of the tracer, which is a key parameter for the quantification of the absorbed doses. The objective of my thesis was precisely to propose new instrumental and methodological approaches aiming to strengthen the control of the dose released to patients during molecular radiotherapy. This is achieved by reducing the uncertainties associated to activity quantification (and therefore to the absorbed dose calculation) through the use of a compact and highly optimized imaging system. Specifically, the work consisted in the development and optimization of a miniaturized, high-resolution mobile gamma camera specifically designed to improve the individual quantitative assessment of the heterogeneous distribution and biokinetics of the radiotracer before and after treatment administration. The study was focused on the treatment of benign and malign thyroid disease with ¹³¹ I. The first prototype of the mobile camera, with a field of view of 5x5 cm², consists of a high-energy parallel- hole collimator, optimized with Monte Carlo simulation and made with 3D printing, coupled to a 6 mm thick continuous CeBr3 scintillator readout by a recent and well-suited technology based on arrays of Silicon Pho- tomultiplier (SiPMs) detectors. Its intrinsic properties, in term of energy and spatial response, have been tested with collimated point source of ⁵⁷Co and ¹³³Ba. The first feasibility prototype has been then calibrated with a line and five cylindrical sources filled with ¹³¹ I. The system calibration leads to an overall spatial resolution of (3.14±0.03) mm at a distance of 5 cm and a sensitivity that decreases with distance and slightly changes with source size. An average sensitivity of (1.23±0.01) cps/MBq has been found at 5 cm. In order to test the quantification capability of the camera, the first preclinical planar studies involved the use of different 3D-printed thyroid phantoms filled with ¹³¹ I, with and without nodules. Although corresponding to a relatively ideal, but realistic, clinical situation (no superimposition of background activity), the optimized imaging features of the camera leads to very promising results, with activity recovery factors that deviate of around 2% from the unity
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Storer, Kingsley Paul School of Medicine UNSW. "Cerebral arteriovenous malformations: molecular biology and enhancement of radiosurgical treatment." Awarded by:University of New South Wales. School of Medicine, 2006. http://handle.unsw.edu.au/1959.4/31942.

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Object Rupture of intracranial arteriovenous malformations is a leading cause of stroke in children and young adults. Treatment options include surgery and highly focused radiation (stereotactic radiosurgery). For large and deep seated lesions, the risks of surgery may be prohibitively high, while radiosurgery has a disappointingly low efficacy and long latency. Radiosurgery carries the most promise for significant advances, however the process by which radiosurgery achieves obliteration is incompletely understood. Inflammation and thrombosis are likely to be important in the radiation response and may be amenable to pharmacological manipulation to improve radiosurgical efficacy. Materials and methods Immunohistochemistry and electron microscopy were used to study normal cerebral vessels, cavernous malformations and AVMs, some of which had previously been irradiated. An attempt was made to culture AVM endothelial cells to study the immediate response of AVM endothelium to radiosurgery. The effects of radiosurgery in a rat model of AVM were studied using immunohistochemistry and the results used to determine the choice of a pharmacological strategy to enhance the thrombotic effects of radiosurgery. Results Vascular malformations have a different endothelial inflammatory phenotype than normal cerebral vessels. Radiosurgery may cause long term changes in inflammatory molecule expression and leads to endothelial loss with exposure of pro-thrombotic molecules. Ultrastructural effects of irradiation include widespread cell loss, smooth muscle cell (SMC) proliferation and thrombosis. Endothelial culture from AVMs proved difficult due to SMC predominance in initial cultures. Radiosurgery upregulated several endothelial inflammatory molecules in the animal model and may induce pro-thrombotic cell membrane alterations. The administration of lipopolysaccharide and soluble tissue factor to rats following radiosurgery led to selective thrombosis of irradiated vessels. Conclusions Inflammation and thrombosis are important in the radiosurgical response of AVMs. Lumen obliteration appears to be mediated by proliferation of cells within the vessel wall and thrombosis. Upregulation of inflammatory molecules and perhaps disruption of the normal phospholipid asymmetry of the endothelial and SMC membranes are some of the earliest responses to radiosurgery. The alterations induced by radiation may be harnessed to selectively initiate thrombus formation. Stimulation of thrombosis may improve the efficacy of radiosurgery, increasing treatable lesion size and reducing latency.
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Stanzani, Elisabetta. "Molecular mechanisms underlying radioresistance of glioblastoma initiating cells." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/401869.

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Glioblastoma (GBM) is the most frequent and malignant primary brain tumor. The current standard of care for adult patient with diagnosed GBM is surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide (TMZ) chemotherapy. Despite intense patient management, conventional therapies are not able to achieve long-term remissions and eventually almost every tumor recurs. The impossibility of extensive tumor debulking, the marked heterogeneity of lesions, the poor drug delivery in the brain and the presence of cancer cells with stem features (Cancer Stem Cells, CSCs) within the bulk of the tumor contribute significantly to the lack of effective treatment options. We ought to develop an in-vitro model to investigate molecular mechanisms underlying GBM resistance based on two major cornerstones: (i) the key duality between Glioblastoma Initiating Cells (GICs) and the bulk of the tumor; and (ii) the intratumoral heterogeneity. Consequently, we conceived a paired model where both GICs and differentiated GBM cells depicting the bulk of the tumor were represented. Both culture models were derived from the same GBM post- surgical specimen, but were established and maintained in different culturing conditions. Moreover, we aimed to design a model that could preserve as much as possible the intratumoral heterogeneity of GBM, within the known limits of in-vitro cultures. Consequently, cultures obtained from GBM specimens were not sorted for expression of putative cancer stem cells markers. Six different GBM patients’ samples were processed and established in-vitro as both Differentiated Glial Cells (DGC) and GICs cultures. Established GICs cultures and corresponding tumor-of-origin were analysed according to the molecular subtypes defined on the basis of transcriptomic signature and both were classified as predominantly Mesenchymal. DGC and GICs deriving from the same patient and growing in cultures as monolayer and neurospheres respectively, were compared side-by-side and stem’s functional features and markers expression were investigated. Neurosphere cultures demonstrated to be enriched in GICs, whereas monolayer cultures were not, as indicated by their poor clonogenic capacity and absent CSCs markers expression. In addition, CSCs markers’ expression patterns highlighted the heterogeneous nature of GICs cultures. Consequently, we demonstated that the neurosphere culture method is a proper approach to isolate GICs within the GBM tumor mass, preserving GICs heterogenic nature. Radiosensitivity of four established culture pairs was investigated by means of clonogenic assay and all established unsorted GICs-enriched cultures ended up being more radioresistant than their differentiated counterparts. Importantly, radiation response of irradiated GICs, but not of DGC, correlates with patient’s outcome, thus supporting the GICs leading role in defining patient treatment response. In conclusion, we propose a quick and affordable method to faithfully determine cancer cells’ treatment response and potentially predict patient outcome based on empirical data. Following clinically relevant fractionated radiotherapy we detected, by means of transcriptomic analysis, marked activation of inflammatory-related pathways, ECM remodeling, cell migration and intercellular crosstalk in GICs. Strikingly, several genes pointed to epithelial/mesenchymal transition processes via IL6/JAK/STAT3 and TNF-α/NFkβ pathways. A small signature of radiation-induced Mes-associated genes was defined in GICs: ICAM1, COX2, CTGF, IL6, LIF and NNMT. In addition, the possible involvement of ITGA6 in GICs response to ionizing radiation was investigated. The knock-down of ITGA6 in GICs-enriched culture enhanced their radiosensitivity, potentially improving tumor radiocurability, and reported decreased capacity to retain stemness after radiotherapy.
El Glioblastoma (GBM) es el tumor cerebral primario maligno más frecuente en adultos. El tratamiento actual, consiste en cirugía seguida de radioterapia (RT) más quimioterapia, no evita las recidivas a largo plazo. Para investigar los mecanismos moleculares que subyacen a la resistencia de GBM a la RT, se ha desarrollado un modelo in-vitro basado en dos pilares fundamentales: (i) la dualidad entre las Glioblastoma Initiating Cells (GICs) y el resto de células neoplásicas (células diferenciadas, DGC); y (ii) la heterogeneidad intratumoral. Los cultivos de GICs y las muestras de tumor homólogas se clasificaron como de tipo mesenquimal. Se compararon los cultivos DGC y GICs por sus características funcionales y metabólicas, la expresión de marcadores de células madres tumorales y la respuesta a la RT. Los cultivos GICs demostraron estar enriquecidos en CSCs, y el patrón de expresión de marcadores de CSCs evidenció su heterogeneidad, a diferencia de lo observado en DGC. Además, todos los cultivos enriquecidos en GICs fueron, a largo plazo, más resistentes a la RT en comparación con sus homólogos diferenciados. Es importante destacar que la radioresistencia de las GICs, pero no de las DGC, se correlaciona con el pronóstico de los pacientes, apoyando así el papel de las GICs en la respuesta al tratamiento. En conclusión, se propone un método rápido y económico para determinar fielmente la respuesta al tratamiento con RT de las células tumorales y potencialmente predecir la evolución del paciente basado en datos empíricos. Para entender mejor el fenómeno de la resistencia a la RT de las GICs se realizó un análisis transcriptómico de DGC y GICs postirradiación. Exclusivamente en las GICs se detectó una activación significativa de las vías relacionadas con la inflamación, remodelación de la matriz extracelular, migración celular, interacción célula-célula y transición epitelio- mesénquima mediado por STAT3 y NF-κβ. Se identificó un grupo de genes asociados al perfil mesenquimal e inducidos por la radiación en GICs: ICAM1, COX2, CTGF, IL-6, LIF y NNMT. Finalmente, se investigó la posible implicación de ITGA6, previamente descrito como marcador de CSCs en GBM, en la respuesta de GICs a la RT. La inhibición de ITGA6 en los cultivos enriquecidos en GICs aumentó la sensibilidad a la RT, mejorando potencialmente la respuesta al tratamiento.
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Books on the topic "Molecular radiotherapy"

1

J, Piccart Martine, ed. Breast cancer and molecular medicine. Berlin: Springer, 2006.

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Molecular imaging for integrated medical therapy and drug development. Tokyo: Springer, 2010.

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Marikki, Laiho, and SpringerLink (Online service), eds. Molecular Determinants of Radiation Response. New York, NY: Springer Science+Business Media, LLC, 2011.

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D, Ford Thomas, ed. New cancer research developments. Hauppauge, NY: Nova Science Publishers, 2009.

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1965-, Shumate Mark J., Kooby David A. 1967-, and Society of Nuclear Medicine (1953- ), eds. A clinician's guide to nuclear oncology: Practical molecular imaging and radionuclide therapies. Reston, VA: SNM, 2007.

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Molls, Michael. The Impact of Tumor Biology on Cancer Treatment and Multidisciplinary Strategies. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009.

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Vohra, Akhtar Abdullah. Observations on intercellular adhesion molecules in patients undergoing radiotherapy for cancer. Manchester: University of Manchester, 1996.

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Cancer Radiotherapy (Methods in Molecular Medicine). Humana Press, 2008.

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Schwaiger, Markus. From Morphological Imaging to Molecular Targeting. Springer, 2013.

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Cordes, Nils, Michael Baumann, and Mechthild Krause. Molecular Radio-Oncology. Springer London, Limited, 2016.

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Book chapters on the topic "Molecular radiotherapy"

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Strigari, Lidia. "Molecular Radiotherapy." In Introduction to Medical Physics, 357–83. Boca Raton: CRC Press, 2021. http://dx.doi.org/10.1201/9780429155758-11.

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Grégoire, Vincent, Karin Haustermans, and John Lee. "Molecular image guided radiotherapy." In Basic Clinical Radiobiology, 254–71. Fifth edition. | Boca Raton, FL : CRC Press/Taylor & Francis Group, [2018]: CRC Press, 2018. http://dx.doi.org/10.1201/9780429490606-22.

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Kwong, Dora L. W., and K. O. Lam. "Radiotherapy for Esophageal Adenocarcinoma." In Methods in Molecular Biology, 7–17. New York, NY: Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-7734-5_2.

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Chang, David S., Foster D. Lasley, Indra J. Das, Marc S. Mendonca, and Joseph R. Dynlacht. "Molecular Biology and Signaling." In Basic Radiotherapy Physics and Biology, 181–89. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-06841-1_17.

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Chang, David S., Foster D. Lasley, Indra J. Das, Marc S. Mendonca, and Joseph R. Dynlacht. "Molecular Biology and Signaling." In Basic Radiotherapy Physics and Biology, 197–206. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-61899-5_19.

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Stokke, Caroline. "Radionuclide Selection for Targeted Molecular Radiotherapy." In Handbook of Radiotherapy Physics, Vol2:1155—Vol2:1160. 2nd ed. Boca Raton: CRC Press, 2021. http://dx.doi.org/10.1201/9780429201493-66.

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Fennell, Jamina Tara, Eleni Gkika, and Anca L. Grosu. "Molecular Imaging in Photon Radiotherapy." In Molecular Imaging in Oncology, 845–63. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-42618-7_27.

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Yazlovitskaya, Eugenia M., and Dennis E. Hallahan. "Molecular Targeted Drug Delivery Radiotherapy." In Molecular Determinants of Radiation Response, 187–200. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4419-8044-1_9.

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Flux, Glenn, and Alan Nahum. "Targeted Molecular Radiotherapy – Clinical Considerations and Dosimetry*." In Handbook of Radiotherapy Physics, Vol2:1161—Vol2:1168. 2nd ed. Boca Raton: CRC Press, 2021. http://dx.doi.org/10.1201/9780429201493-67.

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Chang, David S., Foster D. Lasley, Indra J. Das, Marc S. Mendonca, and Joseph R. Dynlacht. "Cancer Genetic and Molecular Characteristics." In Basic Radiotherapy Physics and Biology, 191–99. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-06841-1_18.

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Conference papers on the topic "Molecular radiotherapy"

1

Kanai, Tatsuaki. "Heavy-ion radiotherapy." In Second international conference on atomic and molecular data and their applications. AIP, 2000. http://dx.doi.org/10.1063/1.1336267.

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Fu, Yabo, Yang Lei, Jun Zhou, Tonghe Wang, David S. Yu, Jonathan J. Beitler, Walter J. Curran, Tian Liu, and Xiaofeng Yang. "Synthetic CT-aided MRI-CT image registration for head and neck radiotherapy." In Biomedical Applications in Molecular, Structural, and Functional Imaging, edited by Barjor S. Gimi and Andrzej Krol. SPIE, 2020. http://dx.doi.org/10.1117/12.2549092.

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Oweida, Ayman J., Jack Xu, Siham Sabri, and Bassam Abdulkarim. "Abstract A66: Ablative radiotherapy increases invasion potential in EGFR-wildtype non-small cell lung cancer cells compared to fractionated radiotherapy." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-a66.

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Fu, Yabo, Yang Lei, Tonghe Wang, Pretesh Patel, Ashesh B. Jani, Hui Mao, Walter J. Curran, Tian Liu, and Xiaofeng Yang. "A learning-based nonrigid MRI-CBCT image registration method for MRI-guided prostate cancer radiotherapy." In Biomedical Applications in Molecular, Structural, and Functional Imaging, edited by Barjor S. Gimi and Andrzej Krol. SPIE, 2021. http://dx.doi.org/10.1117/12.2580786.

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Ungur, Petru, Elisabeta Patcas, Petru A. Pop, Silviu Corbu, and Florin M. Marcu. "Theoretical and Practical Aspects About Bio-Lubrication of Synovial Joints by Radioactive Molecular Treatment." In ASME 2008 9th Biennial Conference on Engineering Systems Design and Analysis. ASMEDC, 2008. http://dx.doi.org/10.1115/esda2008-59160.

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Abstract:
The paper has presented the result of tests and researches realized at our university and Oncology Clinical Hospital from Oradea, Radiotherapy Section, about improving of biolubrication between cartilages in relative moving of synovial joints with osteoarthritis, having slow evolution under non-conventional treatment of irradiation with gamma ray. By radioactive molecular treatment of synovial joints with gamma ray, type hinge of knee and spheres of disorder hip (gon-arthrosis and cox-arthrosis), changed molecular structures of porous cartilages and of synovial fluid in contact. All these due to partial recovering of mechanical-elastic and damper system that was spoiling, with a great reducer of pains, altering some orthopedic and non-conventional treatments at overweight patients, which are been impossible by surgery. This paper has presented a theoretical model of human body subjected the applied and conjunction forces, which explained the damping of vibrations and shocks inside of synovial joints by elastic modulus-E of bone cartilages in contact and variation of dynamic viscosity-η of synovial fluid. This work had proposed to promoted osteoarthritis therapy by using irradiation with gamma ray, being ones of the most modern active molecular treatments by using irradiation with particles in radiotherapy from neurological field.
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Shen, Yuxiaotong, Jie Zhang, Yun Ge, Ying Chen, Haiwei Li, Wei Sun, Mingxi Ji, Quanbo Wei, Jing Cai, and Bing Li. "Clinical feasibility of using an electronic portal imaging device for position verification during conventional radiotherapy." In 2016 IEEE 10th International Conference on Nano/Molecular Medicine and Engineering (NANOMED). IEEE, 2016. http://dx.doi.org/10.1109/nanomed.2016.7883574.

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Fernandes, Jennifer Marx, Anamaria A. Camargo, and Fernanda C. Koyama. "Abstract A51: Evaluation of Akt molecular targets in colorectal tumors after radiotherapy and MK2206 treatment." In Abstracts: AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1557-3265.tcm17-a51.

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Rivera, Sofia, Conchita Vens, Philippe Maingon, Anne Sophie Govaerts, Emad Shash, Denis Lacombe, Warren Grant, and Vincent Grégoire. "Abstract C220: Combining novel targeted therapies and radiotherapy: A challenge to overcome." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-c220.

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Marill, Julie, Naeemunnisa Mohamed, Audrey Darmon, Laurent Levy, Elsa Borghi, Agnès Pottier, and Sébastien Paris. "Abstract LB-A30: Hafnium oxide nanoparticles with radiotherapy induce immunogenic cell death." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; October 26-30, 2017; Philadelphia, PA. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1535-7163.targ-17-lb-a30.

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Ren, Xi, Luca Egoriti, Nolan Esplen, Stephanie Rädel, Brandon Humphries, Hui-Wen Koay, Thomas Planche, et al. "Using in vivo respiratory-gated micro-computed tomography imaging to monitor pulmonary side effects in 10 MV FLASH and conventional radiotherapy." In Biomedical Applications in Molecular, Structural, and Functional Imaging, edited by Barjor S. Gimi and Andrzej Krol. SPIE, 2023. http://dx.doi.org/10.1117/12.2654427.

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Reports on the topic "Molecular radiotherapy"

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Pollack, Alan. The Molecular Mechanism of the Supra-Additive Response of Prostate Cancer to Androgen Ablation and Radiotherapy. Fort Belvoir, VA: Defense Technical Information Center, August 1999. http://dx.doi.org/10.21236/ada377922.

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Song, Kwang. Molecularly Targeted Dose-Enhancement Radiotherapy Using Gold and Luminescent Nanoparticles in an Orthotopic Human Prostate Cancer Rat Model. Fort Belvoir, VA: Defense Technical Information Center, October 2013. http://dx.doi.org/10.21236/ada596724.

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