Dissertations / Theses: 'Cancer ablation'

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Souteyrand, Philippe. "Ablation radioguidée des masses rénales." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM5072/document.

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La prise en charge thérapeutique des tumeurs rénales a considérablement évolué ces dernières années avec l’avènement de traitements mini-invasifs (comme la radiofréquence percutanée) qui optimisent l’épargne néphronique, améliore le confort du patient avec une efficacité oncologique comparable aux traitements chirurgicaux de référence. La prochaine étape serait de proposer des traitements transcutanés aussi performants avec une morbi-mortalité optimisée. L’objectif des travaux réalisés au LIIE du CERIMED (AMU) et au CRCHUM (Université de Montréal) était de développer une alternative à la radiofréquence rénale percutanée que nous utilisons en pratique clinique à Marseille depuis plus de 10 ans et qui a fait ses preuves. Cette alternative doit permettre de traiter des masses rénales avec un niveau d’efficacité et un taux de complications au minimum identique à la RFA, par application transcutanée d’agents physiques sans abord percutané (projet KiTT). Cela passe par la mise au point d’une technique de détection en temps réel de la masse rénale. Nous avons pu développer un algorithme de repérage fiable qui doit encore être optimisé (rapidité de calcul) et être validé sur un modèle qui n’est pas encore disponible. Les travaux d’optimisation et de validation des algorithmes de segmentation, de fonction de mérite de corrélation croisée associée à la fonction d’optimisation Simplex, sont en cours dans le cadre d’une collaboration internationale franco-canadienne au LIIE et au LIO. Même si nous n’avons pas encore la possibilité de proposer ce type de traitement, nos travaux permettent de s’en approcher pour pouvoir les proposer dans les prochaines années
The therapeutic management of renal tumors has changed considerably in recent years with the advent of minimally invasive therapies (such as percutaneous radiofrequency) that maximize nephron savings, improves patient comfort with efficiency comparable to surgical oncology treatments reference. The next step would be to propose transcutaneous treatment (HIFU, stereotactic radiotherapy ...) as efficient with optimized morbidity and mortality.The objective of this work in the context of the LIIE of CERIMED (Aix-Marseille Université) and CRCHUM (Université de Montréal) was to develop an alternative to percutaneous renal radiofrequency we use in clinical practice Marseille for over 10 years and has proved its worth. This alternative must be capable of treating renal masses with a level of effectiveness and complication rates at least equal to the RFA, by applying transcutaneous physical agents without percutaneous approach (project KITT (Kidney Tracking Tumor)). This requires the design of technical point detection in real time of the renal tumor.We were able to develop a reliable identification algorithm that has yet to be optimized (speed of calculation) and be validated on a model that is not yet available. Work optimization and validation of segmentation algorithms, cross correlation merit function associated with Simplex optimization function, are underway as part of an international collaboration to French-Canadian LIIE and LIO.Even if we have not the opportunity to offer this type of treatment, our work allows to approach in order to offer them in the coming years

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Ng, Kwok-chai Kelvin, and 吳國際. "Clinical applications of radiofrequency ablation for hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39557674.

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張飛泉 and Fei-chuen Tzang. "Radiofrequency ablation of hepatocellular carcinoma: identifying prognostic factors in long-term survivaloutcome." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40738711.

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Manner, Cathyryne Kapiolani. "The consequences of CAT2 arginine transporter ablation in cancer and neuropathology /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2003. http://wwwlib.umi.com/cr/ucsd/fullcit?p3091320.

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O'Neill, David Patrick. "Mathematical modelling of the effects of hepatic radiofrequency ablation." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:b9ff47fd-0e1a-4ca6-a937-a7e4d49841ba.

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Liver cancer is a major cause of death worldwide and the impact that it has is set to increase in the coming decades. More than half a million cases are diagnosed each year and it is likely many more sufferers are dying unidentified in parts of the world with poor healthcare. Survival rates for untreated cases after diagnosis are low with few patients living beyond one year. A key cause for low survival rates being that the standard treatment is surgical resection; fewer than one quarter of patients are suitable for invasive surgery and five year survival rates rarely exceeds 66 %. RadioFrequency Ablation (RFA) is a minimally invasive technique which utilises the electrically resistive property of tissue to deposit heat energy locally in the vicinity of the tips of an RFA needle. Heat is transferred away through the tissue by conduction, convection of large blood vessels, and bulk flow of blood in smaller vessels. Liver cells, both cancerous and benign, when exposed to the resultant abnormally high temperatures die considerably more rapidly than in cases of natural hyperthermia. It is thus the radiotherapist’s objective to place the RFA needle in a position that maximises destruction of tumour cells, but minimises the collateral damage of surrounding healthy cells. The learning curve of this nontrivial task is reflected unfavourably in the statistics that relate patient survival rate to clinician experience. In this thesis two mathematical models are presented that could be combined into a ‘global’ model of the effects of RFA. To predict cell death in these conditions under RFA, the O’NeillModel is presented in which cells are accounted for by one of three states: alive, vulnerable, and dead. A mechanistic interpretation of the O’Neill Model is attained through comparison to a model from the literature. A known, but little investigated occurrence of tissue swelling in the annular region peripheral to the ablation volume is modelled in a novel way through equations from the literature that track ion transport across the cell membrane; the O’Neill Model for cell death is also incorporated into this model of oedema.

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Hendricks, Alissa Danielle. "Determining the Oncological and Immunological Effects of Histotripsy for Tumor Ablation." Diss., Virginia Tech, 2021. http://hdl.handle.net/10919/103625.

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Histotripsy is an emerging non-invasive, non-thermal, image-guided cancer ablation modality that has recently been approved for its first clinical trial in the United States (NCT04573881). Histotripsy utilizes focused ultrasound to generate acoustic cavitation within a tumor to mechanically fractionate targeted tissues. While pre-clinical work has demonstrated the feasibility of applying histotripsy to solid tumors including primary liver and renal tumors, there is still a need to investigate the potential of histotripsy to treat additional malignancies. In investigating the potential for treating other malignancies there are two avenues that need to be considered: 1) the feasibility for treating tissues with more complex stromal structures and 2) the ability of histotripsy to modulate the tumor microenvironment. To determine the safety and feasibility of additional applications of histotripsy, we conducted dose studies ex vivo on human tumors and human liver to establish dosimetry metrics for applying histotripsy to more fibrotic tumors such as cholangiocarcinoma while sparing nearby critical structures, such as bile ducts and blood vessels. Learning the safety dose-margins from the excised tissues, we performed an in vivo study using mice bearing patient-derived xenograft cholangiocarcinoma tumors. With this model, we were able to demonstrate our ability ablate the stiff cholangiocarcinoma tumors without causing any debilitating off- target damage. To gain a more robust understanding of the effects of histotripsy ablation on potentially difficult to treat tumors, we developed a porcine xenograft tumor model and utilized veterinary cancer patients. These studies have helped established protocols for utilizing histotripsy with ultrasound guidance to treat tumors that are more difficult to treat and can withstand mechanical ablation, including pancreatic adenocarcinoma, osteosarcomas, and soft tissue sarcomas. Pigs share many similarities with human anatomy and physiology, making them an ideal model organism for testing new medical devices and regimes for treating new targets. Using pigs, we were able to establish a procedure to utilize histotripsy to target the pancreas in vivo without causing any lasting or major side effects, such as off-target damage or pancreatitis. One limitation to the porcine model and veterinary patients, is the limitation of gaining rapid insight into the immunological effects of histotripsy. Established cancer mouse models offer the opportunity to rapidly test many organisms with an intact immune system. We used these mice to study pancreatic adenocarcinoma to determine the immune response after histotripsy ablation. For these tumors the general response was an increase in immune cell infiltration post-treatment and a shift in the tumor microenvironment to a more anti-tumor environment. The results of this dissertation provide insight into establishing protocols for treating new types of tumors with histotripsy and immunological effects that lay groundwork for improving future co-therapeutic treatment planning. Future work will aim to translate histotripsy into clinical applications and determining co-therapies that can help control metastasis.
Doctor of Philosophy
Histotripsy is a new medical therapy that can remove tumors without the need for surgery, with the first clinical trial in the United States starting this year, 2021. This therapy uses focused ultrasound waves to generate powerful microscopic bubbles that can rapidly destroy targeted tissues with a high-degree of precision. Early studies on histotripsy have demonstrated the ability of histotripsy to ablate tumors of the liver and kidneys. In order to be able to fully use this therapy on more difficult to target and treat cancers more studies are needed. Given that histotripsy uses physical forces to destroy targets, stronger, more fibrotic tumors and cancers that have begun to spread throughout the body will be more difficult to treat will need more than simple tumor removal to better treat these patients. Therefore, when investigating new cancer applications of histotripsy, it is important to consider the physical features of the tumors as well as the ability of histotripsy to initiate an immune response against the cancer. To determine the safety and feasibility of additional applications of histotripsy, we conducted dose studies on excised human tumors and human liver to see what doses of histotripsy are required to ablate stronger tumors, such as bile duct tumors. Learning the potential safety margins of doses from the excised tissues, we conducted a study using a mouse model to grow stiff, human tumors. With this model, we were able to show that it is possible to ablate the stiffer tumors without causing any major off-target damage. While it is useful to prove in excised tissues and mice that we can treat certain tumors, there is an additional need to study the therapy in a model that is more similar in size and anatomy to humans. Therefore, to gain a better understanding of the effects of histotripsy on potentially difficult to target and ablate tumors, we developed a novel porcine tumor model that can support the growth of human tumors and utilized veterinary cancer patients. These studies have helped established protocols for utilizing histotripsy to treat difficult to physically ablate tumors and difficult to ultrasound target tumors, including pancreatic and bone cancers. Established cancer mouse models offer the opportunity to rapidly test many organisms with an intact immune system. We used these mice to study pancreatic cancer to determine the immune response after histotripsy ablation. For this tumor type, while there were slight differences, the general response was an increase in immune cell infiltration of the tumors post-treatment and a shift to a stronger immune response against the tumor. The results of this dissertation provide insight into establishing protocols for treating new types of tumors with histotripsy and immune effects that lay groundwork for improving future co-therapeutic planning. Future work will aim to translate histotripsy into clinical applications and determining co-therapies that can help control body-wide disease.

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Ng, Kwok-chai Kelvin, and 吳國際. "Local and systemic effects of hepatic radiofrequency ablation in animal models." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B29434920.

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Klossner, Daniel Patrick. "Improving cryosurgical ablation of advanced state prostate cancer through identification of molecular targets in a prostrate cancer cell model." Diss., Online access via UMI:, 2007.

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Mukherjee, Souvick. "Multiple antenna microwave ablation: impact of non-parallel antenna insertion." Thesis, Kansas State University, 2015. http://hdl.handle.net/2097/19058.

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Master of Science
Department of Electrical and Computer Engineering
Punit Prakash
Microwave ablation is a minimally invasive therapeutic modality used for the treatment of cancer in various organs. In this procedure, microwave energy is sent through a thin antenna placed inside the tumor. The microwave energy radiated from the antenna generates heat which kills the tumor cells by necrosis. During multiple-applicator microwave ablation, geometric estimates of treatment outcome are typically obtained by assuming parallel insertion of the applicators. This assumption is based on the guidelines provided in the brochures of antenna manufacturing companies. This assumption is flawed because it is rare to insert the antennas in parallel configuration due to the flexible nature of the antennas and the presence of intervening organs. Furthermore, movement of patients during the treatment procedure alters the position of the antennas. In order to see the effect of non-parallel insertion of antennas, model-based treatment planning may be instructive. Treatment planning can also determine the changes needed to be made for prospective ablation therapy if the antennas are not positioned in their ideal parallel configuration. This thesis provides a detailed computational comparison of the skewed configurations of microwave antennas to their closest parallel configurations. The metric used for com-paring the similarity between the cases is Dice Similarity Coefficient (DSC). Experimental results to validate the computational data are also discussed. Computations were done by using realistic cases of antenna positions obtained from Rhode Island Hospital.

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Adams, Jacob James. "A coupled electromagnetic-thermal model of heating during radiofrequency ablation." Connect to resource, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1191454972.

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Garcia, Paulo A. "Irreversible Electroporation for the Treatment of Aggressive High-Grade Glioma." Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/77269.

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Malignant gliomas (MG), most notably glioblastoma multiforme (GBM), are among the most aggressive of all malignancies. High-grade variants of this type of brain cancer are generally considered incurable with singular or multimodal therapies. Many patients with GBM die within one year of diagnosis, and the 5-year survival rate in people is approximately 10%. Despite extensive research in diagnostic and therapeutic technologies, very few developments have emerged that significantly improve survival over the last seven decades. Irreversible electroporation (IRE) is a new non-thermal focal tissue ablation technique that uses low-energy electric pulses to destabilize cell membranes, thus achieving tissue death. The procedure is minimally invasive and is performed through small electrodes inserted into the tissue with treatment duration of about one minute. The pulses create an electric field that induces an increase in the resting transmembrane potential (TMP) of the cells in the tissue. The induced increase in the TMP is dependent on the electric pulse parameters. Depending on the magnitude of the induced TMP the electric pulses can have no effect, transiently increase membrane permeability or cause spontaneous death. In this dissertation we hypothesize that irreversible electroporation is capable of ablating normal (gray and white matter) and pathological (MG and/or GBM) brain tissue in a highly focused non-thermal manner that is modulated through pulse parameters and electrode configuration. Through a comprehensive experimental and numerical investigation, we tested and attained results strongly supporting our hypothesis. Specifically, we developed numerical models that were capable of simulating an entire IRE treatment protocol and would take into account pulse parameters (e.g. duration, frequency, repetition rate and strength) in addition to the dynamic changes in tissue electrical conductivity due to electroporation and joule heating, as well as biologically relevant processes such as blood perfusion and metabolic heat. We also provided a method to isolate the IRE effects from undesired thermal damage in models that were validated with real-time temperature measurements during the delivery of the pulses. Finally we outlined a procedure to use 3D volumetric reconstructions of IRE lesions using patient specific MRI scans in conjunction with the models described for establishing field thresholds or performing treatment planning prior to the surgical procedure; thus supplying the readers with the tools and understanding necessary to design appropriate treatment protocols for their specific application. Experimentally we presented the first systematic in vivo study of IRE in normal canine brain and the multimodal treatment of a canine MG patient. We confirmed that the procedure can be applied safely in the brain and was well tolerated clinically. The lesions created with IRE were sub-millimeter in resolution and we achieved 75% tumor volume reduction within 3 days post-IRE in the patient. In addition to the sharp delineation between necrotic and normal brain, the treatments spared the major blood vessels, making it appropriate for treatment of tumors adjacent to, or enveloping critical vascular structures. We believe that irreversible electroporation will play a key role in the treatment of intracranial disorders including malignant brain cancer in which the intent is to focally kill undesired tissue while minimizing damage to surrounding healthy tissue.
Ph. D.

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Nightingale, Joanna. "Investigation of androgen receptor gene transfection into human prostate cancer cells : effects on cellular growth, apoptosis and adhesion." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325852.

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Fors, Gunnar, and Pernilla Arvidsson. "Patienters upplevelser vid datortomografguidad mikrovågsbehandling av tumörer i levern." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-340830.

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Computer tomography (CT) guided ablations of liver tumors using microwaves is a relatively new type of treatment. Studies examining treatment results and complications have been made but how the patients undergoing the treatment experience the care process has not yet been described closely. The aim of this study was thus to describe the experiences of patients undergoing CT-guided ablations of liver tumors using microwaves, focusing on identifying suffering during the time of care. A qualitative method was chosen, with a somewhat deductive approach. Eight semi-structured interviews were held and the data was analyzed using direct content analysis. For deductive application of categories, terms from Katie Erikssons theory on suffering were used. Both experienced actual suffering as well as potential suffering prevented or lessened was identified to present positive as well as negative experiences. The result was identification of suffering of illness such as pain, weariness, mictional dysfunction, breathing difficulties and anxiety directed towards a variety of aspects concerning situation and care; suffering of care such as lack of information, powerlessness, guilt and the feeling of being exposed; suffering of life such as regret and the feeling of mortal threat. Findings also include the opposite of many of the sufferings mentioned above, for example feeling of ease, thankfulness, hope and relieved pain. The conclusion was that the result largely confirms previous findings concerning complications from this kind of surgery as well as patient’s experiences of cancer and going through surgery. The respondents’ overall experience of the healthcare was found to be positive.

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Cho, Je-Yoel. "Characterization of RET/PTC1 Transgenic Mice and development of Cancer Thearpy using Radioiodide Ablation mediated by NA?/I? symporter in Cancers /." The Ohio State University, 1999. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488187763848265.

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Abbass, Mohamed A. M. S. "Real-time Control of Ultrasound Thermal Ablation using Echo Decorrelation Imaging Feedback." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535468911083998.

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Weinberg, Brent D. "Intratumoral Chemotherapy for Liver Cancer Using Biodegradable Polymer Implants." Case Western Reserve University School of Graduate Studies / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1176749922.

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José, Segarra-Martínez Anabel. "Novel approaches against pancreatic cancer based on adenoviral targeting and tumor ablation preclinical evaluation of antitumor efficacy." Doctoral thesis, Universitat Pompeu Fabra, 2011. http://hdl.handle.net/10803/83345.

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Els tractaments actuals pel càncer de pàncreas presenten un eficàcia limitada de manera que es necessari el desenvolupament de noves teràpies antitumorals. La teràpia gènica pel càncer de pàncreas basada en l’ús d’adenovirus es troba limitada per la baixa capacitat dels virus d’arribar a les masses tumoral, de distribuir-se pel tumor i d’infectar les cèl·lules tumorals. Nosaltres hem observat que l’administració intraductal d’adenovirus al ducte biliar de ratolins Ela-myc permet arribar als tumors pancreàtics de manera més eficient que per la via sistèmica. A més a més permet transduir la majoria de la massa tumoral restringint l’expressió adenoviral al teixit pancreàtic. D’altre banda, l’administració intraductal del tractament AduPARTat8TK/GCV retarda significativament el creixement tumoral i disminueix la toxicitat associada al tumor. El nou adenovirus AdTATMMP és activat per les MMP2/9 restaurant la capacitat de transducció de l’AdYTGRE in vitro, i incrementant 7,3 vegades la infecció del tumor pancreàtic. El tractament combinat de l’AduPARTat8TK/GCV amb gemcitabina presenta un efecte sinèrgic in vitro, però no millora la eficàcia antitumoral de les teràpies simples. D’altre banda el tractament de l’electroporació irreversible presenta efectes antitumorals significatius en tumors ortotòpics de la línia cel·lular BxPC-3-Luc i allarga la supervivència dels ratolins provocant una toxicitat mínima.
Novel therapies are needed to overcome the limited efficacy of current treatments in pancreatic cancer. Adenoviral gene therapy against pancreatic tumors is challenged by the limitation of viruses to reach the tumor mass, poorly distribute within the tumor and inefficiently transduce tumor cells. We show that intraductal administration of adenoviruses into the common bile duct of Ela-myc mice targets pancreatic tumors more efficiently than systemic delivery with relevant transduction of the bulk of the tumor and restricts expression to pancreatic tissue. Moreover, intraductal administration of AduPARTat8TK/GCV treatment significantly delayed tumor growth ameliorating tumor-associated toxicity. Noticeable the new generated MMP-activatable adenovirus AdTATMMP was susceptible to MMP2/9 activation, restored the transduction capacity of AdYTRGE in vitro, and increased 7.3 times tumor pancreas transduction. The multimodal treatment AduPARTat8TK/GCV and gemcitabine showed synergistic effects in vitro; however, did not enhance the antitumoral efficacy of single therapies. Interestingly, IRE treatment exhibited significant antitumor effects in BxPC-3-Luc orthotopic tumors and prolonged mice survival with minimal toxicity.

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Dunn, Andrew W. "Hyperthermic ablation of MDA-MB-231 human mammary gland adenocarcinoma mediated by the photothermal effect of poly(acrylic acid) coated magnetite nanoparticles, efficacy and applicability for novel cancer treatment." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1384849962.

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Nandlall, Sacha D. "Monitoring cell and tissue damage during ablation by high-intensity focussed ultrasound." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:033693cc-237d-4f84-a891-f121c8e94465.

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High Intensity Focussed Ultrasound (HIFU) ablation is a promising technology for the non-invasive, targeted treatment of certain types of cancer. The technique functions by subjecting tumours to a cytotoxic level of intense, localised heating, while leaving the surrounding tissue unharmed. However, a number of limitations in the available HIFU treatment monitoring methods are currently hampering the effectiveness and clinical adoption of the therapy. This work aims to develop improved metrics of HIFU-induced biological damage that are specifically suited to monitoring and controlling HIFU ablation. Firstly, an optical method that enables straightforward quantification of thermal damage in protein-embedding hydrogels is developed. Secondly, hydrogels embedded with different cell lines are used to assess the performance of common temperature-based metrics of cell death across a range of HIFU-relevant conditions. Finally, a novel, passive acoustic detector designed for the real-time monitoring of HIFU-induced tissue damage is proposed. The detector is shown to predict lesioning with over 80% accuracy in regimes that are very likely to create lesions (60 J of acoustic energy or more), with an error rate of less than 6% for exposures that are too short to cause lesioning (up to 1 s long). The proposed detector could therefore provide a low-cost means of effectively monitoring clinical HIFU treatments passively and in real time.

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Holroyd, David. "Effect of blood flow on high intensity focused ultrasound therapy in an isolated, perfused liver model." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:89f8f435-373d-46c2-92c8-5e9d21b4f01d.

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High intensity focused ultrasound (HIFU) is an emerging non-invasive thermal ablative modality that can be utilised for the treatment of solid organ tumours, including liver cancer. Acoustic cavitation is a phenomenon that can occur during HIFU and its presence can enhance heating rates. One major limitation of thermal ablative techniques in general, such as radiofrequency and microwave ablation, is the heat sink effect imparted by large vasculature. Thermal advection from blood flow in vessels ≥ 3 - 4 mm in diameter has been shown to significantly reduce heating rates and peak temperatures in the target tissue, potentially leading to treatment failure. With regards to HIFU therapy, a clearer understanding is required of the effects of blood flow on heating, cavitation and thermal tissue necrosis, which is the treatment endpoint in clinical thermal ablation. Therefore, the overall aim of this thesis project was to elucidate the effects of blood flow on HIFU-induced heating, cavitation and histological assessment of thermal ablation. A unique isolated, perfused porcine liver model was used in order to provide a relevant test bed, with physiological and anatomical characteristics similar to the in vivo human liver. The normothermic liver perfusion device used in all studies presented in this work can keep an organ alive in a functional state ex vivo for in excess of 72 hours. A further advantage of the liver perfusion device was that it allowed blood flow to be stopped completely and resumed rapidly, allowing studies to be conducted under zero flow conditions. A therapeutic HIFU system was used in order to deliver HIFU therapy to regions of hepatic parenchyma adjacent (≤ 3 mm) to large (≥ 5 mm) blood vessels or away from vasculature (≥ 1 cm) at either 1.06 MHz or at 3.18 MHz. Cavitation events during HIFU therapy were spatio-temporally monitored using a previously developed passive acoustic mapping (PAM) technique. The cavitation threshold at each frequency was determined through assessment of acoustic emissions acquired through PAM during HIFU exposure at a range of acoustic pressures. Real time thermal data during HIFU therapy were obtained using an implantable 400 μm thermocouple, aligned with the HIFU focus, in order to assess the effect of large vessel blood flow on peak tissue temperatures. Thermal data were obtained at 1.06 MHz, in the presence of acoustic cavitation and at 3.18 MHz, in the absence of cavitation, both in the presence and complete absence of blood flow. Finally, histological assessment of cell viability and cell death was performed in order to determine whether any heat sink effect could be overcome, with the achievement of complete tissue necrosis in treatment regions directly adjacent to large vasculature. This work demonstrated for the first time that in perfused, functional liver tissue, the presence of large vasculature and physiological blood flow does not significantly affect ablative HIFU therapy, both in terms of peak focal tissue temperatures attained and histological evidence of complete tissue necrosis. Therefore, HIFU may be superior to other ablative modalities in treating tumours in tissue regions adjacent to major vascular structures, but further work needs to be performed to correlate the experimental findings with clinical outcomes.

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Seror, Oliver. "Adaptation et évaluation du monitorage par IRM de température des ablations hépatiques par radiofréquence." Bordeaux 2, 2006. http://www.theses.fr/2006BOR21331.

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Dans ce travail la faisabilité et la précision de l'IRM de température reposant sur la mesure la variation thermo dépendante de la fréquence de résonance des protons de l'eau (PRF) est évaluée pour le monitoring des ablatons hépatiques par radiofréquence. Trois étapes expérimentales précèdent la réalisation d'une étude clinique pilote : une étude ex vivo sur échantillons de foie, une série d'ablation in vivo dans le foie de lapin, une série d'ablations in vivo dans le foie de porc avec du matériel de radiofréquence clinique et enfin une série de huit patients traités pour tumeurs hépatiques par radiofréquence sous contrôle continu d'IRM de température. Nos résultats montrent que l'IRM de température est une technique de monitoring à la fois faisable et fiable pour monitorer en temps réel les ablations hépatiques par radiofréquence. Des modifications de la technique d'imagerie et du matériel de radiofréquence devraient améliorer l'opérationnalité de ce nouveau ttype de monitoring
In this work the feasibility and the accuracy of MR-thermometry based on the proton resonance frequency shift and using the concept of thermal dose for the monitoring of radiofrequency ablation in the liver were assed. Before the achievement of a clinical pilot study, we carried out three experimental studies : the first was performed ex vivo on liver samples, the second in vivo in the liver of rabbits and the third in vivo in the liver of pigs using clinical available radiofrequency material. Finally the clinical study consisted of the treatment of malignant liver tumours of eight patients by radiofrequency ablation under continuous MR-thermometry monitoring. At each steps of this work Mr-thermometry appeared as a faeasible and reliable monitoring technique to assess in real time the extent of ablation zone during radiofrequency ablation. Further changes in imaging protocol and in the radiofrequency material might improve significantly the effectiveness of this new monitoring imaging

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Leboulleux, Sophie. "Place de l'iode 131 et de l'imagerie scintigraphique dans la prise en charge des cancers différenciés de la thyroïde." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T062.

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Le traitement initial des cancers différenciés de la thyroïde (CTD) consiste en une thyroïdectomie totale suivie, dans de nombreux cas par l’administration d’iode 131. Après thyroïdectomie totale, un traitement par iode 131 est indiqué en fonction des caractéristiques tumorales initiales. Chez les patients à risque élevé de rechute il est recommandé d’administrer une forte activité d’iode 131. Chez les patients à très faible risque il est recommandé de ne pas administrer d’iode 131. Dans le groupe intermédiaire, il a été montré par deux études prospectives multicentriques randomisées (ESTIMABL et HILO) qu’une activité de 1,1 GBq (30 mCi) administrée après TSHrh (Thyroid Stimulating Hormon recombinante humaine) était adaptée. La désescalade thérapeutique se poursuit dans le cadre d’un autre essai prospectif randomisé (ESTIMABL 2) comparant une activité de 30 mCi après injection de TSHrh à une simple surveillance. Chez les patients avec maladie résiduelle la tomographie par émission de positon couplée à un scanner (TEP/TDM) au fluorodesoxyglucose (FDG) est un examen clé avec une valeur à la fois diagnostique et thérapeutique. Les fixations de FDG permettent de localiser la maladie résiduelle, surtout lorsqu’elle ne capte pas l’iode. Chez les patients dont le site de récidive n’est pas déterminé par l’échographie cervicale, la TEP/TDM au FDG est plus sensible que la scintigraphie post-thérapeutique réalisée après administration d’une forte activité d’iode 131 (dite activité empirique) et est considéré comme l’examen de première intention. La réalisation d’une stimulation par TSHrh avant la TEP au FDG augmente le nombre de lésions détectées et donc sa sensibilité sans que les modifications thérapeutiques qui en découlent soient néanmoins significatives. Le rôle de la TEP FDG dans la sélection des patients nécessitant un traitement par inhibiteur de tyrosine kinase et dans l’évaluation antitumorale des inhibiteurs de tyrosine kinase reste à démontrer. L’utilisation d’ITK pour ré-induire les fixations d’iode 131 sont une voie majeure de développement pour les patients ayant une maladie réfractaire à l’iode 131
Initial treatment of differentiated thyroid cancer is based on a total thyroidectomy and in many cases on the administration of radioactive iodine. Following total thyroidectomy, radioactive iodine is given, based on the primary tumor characteristics. In case of a very low risk of recurrence it is recommended not to give radioactive treatment. In case of high risk patients, a high activity of radioactive iodine is given after TSH stimulation. In case of intermediate risk patients, two randomized prospective studies (ESTIMABL and HILO) have shown that an activity of 1,1 GBq (30 mCi) given after rhTSH (recombinant human Thyroid Stimulating Hormon) was adequate. A further step is taken towards less treatment has now been undertaken with the ESTIMABL2 study, a prospective randomized study comparing a treatment with 1,1 GBq (30 mCi) of radioactive iodine treatment to follow-up without ablation. In patients with persistent disease, positron emission tomography with computed tomography (PET/CT) is a key examination used for its diagnostic and prognostic value. Foci of FDG uptake can localize residual disease, especially when it does not take up radioactive iodine. In patients in whom the site of recurrence remains unknown after a neck ultrasonography PET/CT with FDG is more sensitive than a post-therapeutic whole body scan performed after the administration of a high activity of radioactive iodine (empiric iodine) and should be considered as the first examination to perform. Injections of rhTSH before doing FDG PET/CT allow to increase the number of lesions detected, however the treatment changes linked to this preparation remains minor. The role of FDG PET/CT in the selection of patients to tyrosine kinase inhibitors (TKI) and to assess metabolic tumor response remains to be explored. The use of TKI to reinduce radioactive iodine uptake is a major research subject for patients with radioactive iodine refractory disease

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Lindberg, Mallory E. "THE IMPACT OF E-CADHERIN AND PHOSPHATASE AND TENSIN HOMOLOG ABLATION IN THE UTERUS: THE PROGRESSION OF TYPE I ENDOMETRIAL CARCINOMA." OpenSIUC, 2014. https://opensiuc.lib.siu.edu/theses/1411.

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E-&ndashcadherin (CDH1) is a cell adhesion molecule that coordinates key morphogenetic processes regulating cell growth, cell proliferation and apoptosis. Loss of CDH1 is a trademark of the cellular event epithelial to mesenchymal transition (EMT), which increases the metastatic potential of malignant cells. PTEN is a tumor suppressor gene commonly mutated in many human cancers, including endometrial cancer. In the mouse uterus, ablation of Pten induces epithelial hyperplasia, leading to endometrial carcinomas. However, loss of Pten alone does not affect longevity until around 5 months. Similarly, conditional ablation of Cdh1 alone does not predispose mice to cancer. We characterized the impact of dual Cdh1 and Pten ablation using Pgr-Cre (Cdh1d/d Ptend/d) in the mouse uterus. We observed that Cdh1d/d Ptend/d mice died at postnatal day 15-&ndash19 with massive blood loss from their reproductive tract (abnormal metrorrhagia) with prevalent vascularization in both the endometrium and myometrium. Their uteri were abnormally structured with curly horns, disorganized epithelial structure, and increased cell proliferation. Co-&ndashimmunostaining of KRT8 and ACTA2 showed invasion of epithelial cells into the myometrium. Further, the uteri of Cdh1d/d Ptend/d mice had prevalent vascularization in both the endometrium and myometrium. We also observed reduced expression of estrogen and progesterone receptors, loss of cell adherens and tight junction molecules (CTNNB1 and claudin), as well as activation of AKT in the uteri of Cdh1d/d Ptend/d mice. However, complex hyperplasia was not found in the uteri of Cdh1d/d Ptend/d. Collectively, these findings suggest that ablation of Pten with Cdh1 in the uterus accelerates cellular invasiveness and angiogenesis, and causes early death. Thus, this model does not allow sufficient time for the emergence of advanced, clinically over aggressive endometrial tumorigenesis and metastasis. Additionally, we looked at a new Cre system to ablate Pten and Cdh1 only in the epithelial cells of the uterus. Sprr2f, an estrogen dependent gene that is found highly expressed in the uterus, helps with structure and barrier function of epithelial cells. Prg-Cre turns on at postnatal day 3-5 before development of the uterus; whereas, Sprr2f-Cre is active around 3 weeks which is after uterine development. We have driven the ablation of Cdh1d/d Ptend/d using the Sprr2f-Cre. The Sprr2f-Cre Cdh1d/d Ptend/d mice successfully lived to 2 months. The Sprr2f-Cre Ptend/d mice displayed hyperplastic epithelial cells, most prominently in the glandular like structures of the uterus. Lack of cellular structure was observed in the Sprr2f-Cre Cdh1d/d Ptend/d mice. We also developed a model of orthotopic tumor transplantation to study further tumor development including cell invasion, dissemination and metastasis. The uteri of control, Cdhd/d, Ptend/d and Cdhd/d Ptend/d mice were collected and dissected to approximately ~1 mm in diameter. Then, the tissue fragments were orthotopically implanted into the uterine wall (endometrium) of wild-type syngeneic host mice. We have observed successful implantation and sustainability of the tissue through this technique. The tissue viability was successfully verified by implanting donor uterine pieces under the kidney capsule of recipient wild type mice. This study has shown that the ablation of Cdh1 and Pten in the mouse uterus initiates a more aggressive form of type I endometrial carcinoma when using Pgr-Cre as well as Sprr2f-Cre. However, neither conditional ablation approaches allowed us to fully observe the progression of the carcinoma to a metastatic disease. Our intrauterine endometrial/myometrial implantation technique proved to be an incomplete method to further study the metastatic potential of the PgrCre/+ Cdh1f/f Ptenf/f mice.

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24

Salomir, Rares. "Local hyperthermia by MRI-guided focused ultrasound : fast MR-thermometry and on-line temperature control : feasibility studies of tumor thermal ablation." Bordeaux 1, 2001. http://www.theses.fr/2001BOR12418.

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La destruction locale de tumeurs sous contrôle IRM offre une nouvelle altérnative aux traite-ments classiques du cancer comme la chirurgie, la radio- et la chimio-thérapie. Parmi toutes les modalités d'induction d'une hyperthermie locale, seuls les ultrasons focalisés (USF) per-mettent une approche non-invasive. Le contrôle IRM de l'hyperthermie locale nécessite une cartographie de température rapide et fiable. La méthode basée sur la fréquence de résonance de protons de l'eau est préférée en raison de sa linéarité et de son indépendance par rapport à la nature du tissu. Les modifications locales dans la susceptibilité magnétique, ainsi que les mouvements du tissu, peuvent engendrer des erreurs dans les cartes de température obtenues par cette méthode. Des techniques de correction temps-réel sont donc demandées. La cartogra-phie rapide de température par IRM permet le contrôle temps-réel de la température au point focal. Le traitement de volumes grands par rapport à la zone focale peut être accompli par un déplacement du point focal le long d'une trajectoire optimisée, alors que le faisceau USF est émis en mode continu. Cette méthode conduit à une destruction uniforme et contigue du volume tumoral et réduit considérablement la durée du traitement, conformément aux résultats obtenus sur le carcinome VX2 implanté chez le lapin. La technologie des émetteurs en réseau phasé devrait améliorer les performances de cette méthode de chauffage. Les premiers essais cliniques chez l'homme concerneront probablement le traitement de tumeurs du sein.

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Wharton, Iain Philip. "The design and development of a transrectal high-intensity focused ultrasound probe for magnetic resonance guided ablation of localised prostate cancer." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506040.

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Zhang, Yu. "Photothermal effect of PS coated Fe3O4 nanoparticles via near-infrared laser and effect of mimic body tissue depth on hyperthermic ablation of MDA-MB-231." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1445343075.

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Souchon, Rémi. "Application de l'élastographie à l'imagerie du cancer de la prostate et à sa thérapie par ultrasons focalisés." Lyon, INSA, 2004. http://theses.insa-lyon.fr/publication/2004ISAL0018/these.pdf.

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Un système d'imagerie de la prostate par élastographie ultrasonore a été développé. Il utilise un ballon rempli d'un liquide de couplage ultrasonore pour comprimer la prostate. La faisabilité de visualiser l'anatomie prostatique ainsi que des tumeurs bénignes et malignes de la prostate in vitro est démontrée. L'importance de la rapidité de l'acquisition pour obtenir des images de qualité in vivo est ensuite mise en évidence. Il est alors montré que ce système permet de détecter le cancer et de visualiser les effets de la thérapie par ultrasons focalisés de haute intensité (HIFU) in vivo. Enfin il est montré in vitro qu'il est possible de visualiser la formation d'une lésion HIFU élémentaire en utilisant seulement l'élévation de température pour former l'image
An ultrasonic imaging device for prostate elastography was developed. A balloon filled with a coupling liquid served as a compressor. In vitro, the system was capable of imaging the anatomy of the prostate as well as benign and malignant tumors. Then the major influence of the acquisition frame on the image quality in vivo was demonstrated. The system was shown to be able to detect prostate cancer and to visualize the effects of high intensity focused ultrasound (HIFU) therapy in vivo. It was finally shown in vitro that the formation of an elementary HIFU lesion could be observed by passive elastography, using only temperature elevation to create the elastogram

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Luco, Aimee-Lee. "Vitamin D strongly influences skeletal metastasis development in breast cancer: comparison of systemic vitamin D deficiency versus local ablation of CYP27B1 in breast tumour cells." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121223.

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Vitamin D is very well known for its classical role in the maintenance of calcium and phosphorus homeostasis as well as in the prevention of rickets. More recent findings of its ability to inhibit cell proliferation, induce apoptosis, induce differentiation, inhibit angiogenesis, and modulate the immune system have made it a current topic of intense research, particularly in the field of cancer research. We used a murine model of breast cancer metastasis to bone to investigate the effect of vitamin D deficiency on the growth of breast cancer tumour cells within bone. We also established that these breast cancer tumour cells express the enzyme CYP27B1 (1α-hydroxylase) which is able to convert the inactive vitamin D precursor 25-hydroxyvitamin D (25(OH)D) to the active metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D). We next examined the effect of the local activation of vitamin D by tumoral CYP27B1 on the growth of these tumour cells within bone. Although we did not see a significant difference in the growth of breast cancer tumour cells in the bones of vitamin D deficient mice as compared to vitamin D sufficient mice, we have demonstrated that breast cancer tumour cells that do not express CYP27B1 grow much more aggressively within bone than breast cancer tumour cells which express CYP27B1. This suggests a very important role for the local activation of vitamin D by extra-renal CYP27B1 on the growth of breast cancer tumour cells within the bone microenvironment. These findings suggest a potential use for 25(OH)D as a treatment for breast cancer metastasis to bone either alone or in combination.
La vitamine D est bien connue pour son rôle dans le maintien des concentrations de calcium et du phosphore dans la circulation ainsi que dans la prévention du rachitisme. La découverte plus récente de sa capacité d'inhiber la prolifération cellulaire, induire leur différentiation ainsi que l'apoptose cellulaire, inhiber l'angiogenèse, et moduler le système immunitaire rend son étude un sujet de recherche très intéressant surtout dans le domaine de la recherche sur le cancer. Nous avons étudié l'effet de la carence en vitamine D sur la croissance tumorale dans un modèle murin de métastases osseuses du cancer du sein. Nous avons aussi établi que ces cellules expriment l'enzyme CYP27B1 (1α-hydroxylase) et sont donc capables d'activer la vitamine D en son métabolite actif la 1,25-dihydroxyvitamine D (1,25(OH)2D) à partir du métabolite inactif, la 25-hydroxyvitamine D (25(OH)D). Nous avons ensuite examiné l'effet de l'activation locale de la vitamine D par les cellules tumorales dérivées du sein sur la croissance de ces cellules dans le microenvironnement osseux. Nous n'avons constaté aucune différence significative entre la croissance des cellules tumorales du cancer du sein dans l'os chez les souris carencées en vitamine D en comparaison aux souris non carencées en vitamine D. Cependant, nous avons démontré que les cellules tumorales du cancer du sein qui expriment le CYP27B1 croissent beaucoup moins vite dans l'os que les cellules tumorales qui n'expriment pas le CYP27B1. Ces résultats suggèrent un rôle très important de l'activation extra-rénale de la vitamine D par les cellules tumorales du cancer du sein pour inhiber la croissance de ces cellules dans l'os. En conclusion, ces travaux indiquent que le précurseur inactif 25(OH)D pourrait être utilisé seul ou en combinaison pour le traitement des métastases osseuses du cancer du sein.

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Neal, II Robert Evans. "Irreversible Electroporation Therapy for the Treatment of Spontaneous Tumors in Cancer Patients." Diss., Virginia Tech, 2011. http://hdl.handle.net/10919/51741.

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Irreversible electroporation is a minimally invasive technique for the non-thermal destruction of cells in a targeted volume of tissue, using brief electric pulses, (~100 µs long) delivered through electrodes placed into or around the targeted region. These electric pulses destabilize the integrity of the cell membrane, resulting in the creation of nanoscale defects that increase a cell’s permeability to exchange with its environment. When the energy of the pulses is high enough, the cell cannot recover from these effects and dies in a non-thermal manner that does not damage neighboring structures, including the extracellular matrix. IRE has been shown to spare the major vasculature, myelin sheaths, and other supporting tissues, permitting its use in proximity to these vital structures. This technique has been proposed to be harnessed as an advantageous non-thermal focal ablation technique for diseased tissues, including tumors. IRE electric pulses may be delivered through small (ø ≈ 1 mm) needle electrodes, making treatments minimally invasive and easy to apply. There is sub-millimeter demarcation between treated and unaffected cells, which may be correlated with the electric field to which the tissue is exposed, enabling numerical predictions to facilitate treatment planning. Immediate changes in the cellular and tissue structure allow real-time monitoring of affected volumes with imaging techniques such as computed tomography, magnetic resonance imaging, electrical impedance tomography, or ultrasound. The ability to kill tumor cells has been shown to be independent of a functioning immune system, though an immune response seems to be promoted by the ablation. Treatments are unaltered by blood flow and the electric pulses may be administered quickly (~ 5 min). Recently, safety and case studies using IRE for tumor therapy in animal and human patients have shown promising results. Apart from these new studies, previous work with IRE has involved studies in healthy tissues and small cutaneous experimental tumors. As a result, there remain significant differences that must be considered when translating this ablation technique towards a successful and reliable therapeutic option for patients. The dissertation work presented here is designed to develop irreversible electroporation into a robust, clinically viable treatment modality for targeted regions of diseased tissue, with an emphasis on tumors. This includes examining and creating proving the efficacy for IRE therapy when presented with the many complexities that present themselves in real-world clinical patient therapies, including heterogeneous environments, large and irregular tumor geometries, and dynamic tissue properties resulting from treatment. The impact of these factors were theoretically tested using preliminary in vitro work and numerical modeling to determine the feasibility of IRE therapy in heterogeneous systems. The feasibility of use was validated in vivo with the successful treatment of human mammary carcinomas orthotopically implanted in the mammary fat pad of mice using a simple, single needle electrode design easily translatable to clinical environments. Following preliminary theoretical and experimental work, this dissertation considers the most effective and accurate treatment planning strategies for developing optimal therapeutic outcomes. It also experimentally characterizes the dynamic changes in tissue properties that result from the effects of IRE therapy using ex vivo porcine renal cortical tissue and incorporates these into a revised treatment planning model. The ability to use the developments from this earlier work is empirically tested in the treatment of a large sarcoma in a canine patient that was surgically unresectable due to its proximity to critical arteries and the sciatic nerve. The tumor was a large and irregular shape, located in a heterogeneous environment. Treatment planning was performed and the therapy carried out, ultimately resulting in the patient being in complete remission for 14 months at the time of composing this work. The work presented in this dissertation finishes by examining potential supplements to enhance IRE therapy, including the presence of an inherent tumor-specific patient immune response and the addition of adjuvant therapeutic modalities.
Ph. D.

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Thomas, Sean Casey. "A Developed and Characterized Orthotopic Rat Glioblastoma Multiforme Model." Thesis, Virginia Tech, 2020. http://hdl.handle.net/10919/100772.

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This thesis project serves to fill experimental gaps needed to advance the goal of performing pre-clinical trials using an orthotopic rat glioblastoma model to evaluate the efficacy of high-frequency electroporation (H-FIRE) and QUAD-CTX tumor receptor-targeted cytotoxic conjugate therapies, individually and in combination, in selectively and thoroughly treating glioblastoma multiforme. In order to achieve this, an appropriate model must be developed and characterized. I have transduced F98 rat glioma cells to express red-shifted firefly luciferase, which will facilitate longitudinal tumor monitoring in vivo through bioluminescent imaging. I have characterized their response to H-FIRE relative to DI TNC1 rat astrocytes. I have demonstrated the presence of the molecular targets of QUAD in F98 cells. The in vitro characterization of this model has enabled preclinical studies of this promising glioblastoma therapy in an immunocompetent rat model, an important step before advancing ultimately to clinical human trials.
Master of Science
Treating glioblastoma multiforme (GBM), a form of cancer found in the brain, has not been very successful; patients rarely live two years following diagnosis, and there have been no major breakthrough advances in treatment to improve this outlook for decades. We have been working on two treatments which we hope to combine. The first is high-frequency electroporation (H-FIRE), which uses electrical pulses to kill GBM cells while leaving healthy cells alive and blood vessels intact. The second is QUAD-CTX, which combines a toxin with two types of protein that attach to other proteins that are more common on the surface of GBM cells than healthy cells. We have shown these to be effective at disproportionately killing human GBM cells growing in a lab setting. Before H-FIRE and QUAD-CTX may be tested on humans, we need to show them to be effective in an animal model, specifically rats. I have chosen rat glioma cells that will behave similarly to human GBM and a rat species that will not have an immune response to them. I have made these cells bioluminescent so that we may monitor the tumors as they grow and respond to our treatments. I have also shown that QUAD-CTX kills these rat glioma cells, as does H-FIRE. Because of this work, we are ready to begin testing these two treatments in rats.

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Lemdani, Kathia. "Optimisation de la réponse immune après traitement locorégional de tumeurs colorectales murines." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS374.

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Les métastases hépatiques compliquent l'évolution de 50% des cancers colorectaux (CCR). Plus de la moitié des patients présentent une récidive à distance avec métastases occultes pour lesquelles une chirurgie peut être réalisée dans moins de 20% des cas. L'ablation par radiofréquence (RFA) induit une réponse lymphocytaire T qui n'est pas évaluée après une intervention chirurgicale seule. L'immunothérapie combinée à la RFA pourrait potentialiser cet effet conduisant à une réponse tumorale à distance. Nous proposons une approche qui combine la RFA avec hydrogel thermoreversible libérant des agents immunomodulateurs (GMCSF et BCG) sur le site du traitementPremièrement, nous nous sommes intéressés à la sélection et à la caractérisation de la formulation optimale d’hydrogel par des techniques physicochimiques. Les propriétés de l'hydrogel ont été étudiées par rhéologie et des tests de muco-adhésion ont été mis en place. Le temps de résidence de l'hydrogel et de la protéine dans la zone tumorale a été démontré par imagerie optique. De plus, la cinétique de libération et l'intégrité du GMCSF encapsulé ont été déterminées. Ensuite, nous avons démontré l’efficacité de l’association de la RFA avec le dépôt local de l’hydrogel immunomodulatuer sur un modèle murin de cancer colorectal. En effet, nous avons observé une survie améliorée des animaux et régression complète des tumeurs distantes chez les animaux traités par la combinaison complète. Cette réponse est caractérisée par un niveau élevé de sécrétion de cytokines pro-inflammatoires par les cellules T CD4 et TCD8 et une augmentation de l’infiltrat lymphocytaire dans les tumeurs. Ceci a permis d'envisager une association avec l'immunothérapie anti-PD1 dans le traitement de macrométastases échappant au traitement combiné RFA avec l’hydrogel immunomodulateur. En effet, l’immunothérapie dans le traitement du cancer colorectal métastatique présente une efficacité limitée chez les patients. Notre travail propose a démontré que l’efficacité de l’immunomodulation locale dans l’amélioration des réponses immunitaires dans le cancer colorectal. Ces résultats permettent de reconsidérer l’utilisation de l’immunothérapie chez les patients atteints de CCR métastatique non MSI
Liver metastases complicate the progression of 50% of colorectal cancers (CRC). More than half of the patients have recurrent remissions with occult metastases for which surgery can be performed in less than 20% of cases. Radiofrequency ablation (RFA) induces a T lymphocyte response that is not observed after surgery alone. Combined immunotherapy with RFA may potentiate this effect leading to a distant tumor response. We propose an approach that combines RFA with thermoreversible hydrogel releasing immunomodulatory agents (GMCSF and BCG) at the treatment site.First, we focused on the selection and characterization of the optimal hydrogel formulation by physicochemical techniques. The properties of the hydrogel were studied by rheology and mucoadhesion tests were set up. The residence time of the hydrogel and the protein in the tumor zone was demonstrated by optical imaging. In addition, the release kinetics and integrity of the encapsulated GMCSF were determined. Then, we demonstrated the effectiveness of the combination of RFA with the local deposition of the immunomodulatory hydrogel on a mouse model of colorectal cancer. Indeed, we observed improved survival of animals and complete regression of distant tumors the complete treatment group. This response is characterized by a high level of pro-inflammatory cytokine secreted by CD4 and TCD8 T cells and an increase Lymphocytes infiltrating tumors. The immune escape of large lesions was reversed by association with anti-PD1 immunotherapy Indeed, immunotherapy in the treatment of metastatic colorectal cancer has limited efficacy in patients. Our work has demonstrated the effectiveness of local immunomodulation in improving immune responses in colorectal cancer. These results make it possible to reconsider the use of immunotherapy in patients with non-MSI metastatic CRC

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32

Prudhomme, Michel. "Traitement des tumeurs hépatiques par thermothérapie interstitielle induite par le laser diode." Montpellier 1, 2000. http://www.theses.fr/2000MON1T020.

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Lourette, Natacha Madeleine Germaine. "Analyse in situ de cellules imprégnées de photosensibilisants par ablation / ionisation laser couplée à la spectrométrie de masse : Application en thérapie photodynamique des cancers." Metz, 2004. http://www.theses.fr/2004METZ036S.

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A 5,10,15,20 meso(tetrahydroxyphényl)bacterio-chlorine (m-THPBC), la chlorine (m-THPC) et la porphyrine (m-THPP) équivalentes, sont employées comme agents photosensibles en thérapie photodynamique des cancers (PDT). Nos travaux ont été axés sur la m-THPC qui possède la plus grande activité photochimique. En vue d'une étude in vitro par MALDI-TOFMS, nous avons tout d'abord analysé ce photosensibilisant en milieu aqueux. Suite à une illumination laser à 650nm, les principales réactions observées ont été l'hydroxylation ou l'oxydation de la m-THPC et une déshydrogénation de la molécule en m-THPP. L'irradiation à 647,5 nm de la m-THPP a notamment révélé la formation de multimères covalents provenant de processus d'agrégations. Ces agrégats ont fait l'objet d'une étude structurale. Puis, nous avons utilisé une sonde chimique (DPBF) pour mettre en évidence la formation d'oxygène moléculaire singulet 1O2 pendant l'irradiation de la m-THPC. De la sorte, il a été montré tant en milieu éthanolique qu'aqueux, qu'une analyse MALDI-TOFMS permettait de caractériser simultanément la m-THPC, la DPBF et leurs photoproduits respectifs. Enfin pour comprendre les différents processus de photodégradation de la m-THPC in vitro, nous avons optimisé un protocole d'analyse par MALDI-TOFMS de cellules adhérentes intactes. Ainsi, nous avons identifié in situ des photoproduits oxydés et des traces de m-THPP, suite à l'irradiation par diode laser (652nm) de cellules incubées avec de la m-THPC (2µg/mL). L'extension de ce protocole à d'autres applications a permis de différencier de façon spécifique et reproductible différentes souches cellulaires cancéreuses par leur empreinte protéique
The 5,10,15,20-tetrakis(mesohydroxyphenyl) porphyrin series (m-THPP, m-THPC, and m-THPBC) have attracted interest as possible photosensitizers in PDT owing to their strong absorption in the red region combined with their tumor localizing properties. The m-THPC (FOSCAN, temoporfin), is one of the most efficient prospective sensitizers, although, until recently, there has been little information on the nature of its photoproducts. In aqueous medium, opening studies were carried out by MALDI-TOFMS. After laser irradiation at 650nm, hydroxides and oxides of m-THPC were detected. In addition, m-THPC dehydrogenization into m-THPP was observed. Subsequently, the laser irradiation (647. 5nm) of m-THPP revealed the formation of covalent multimers due to aggregation process. A preliminary structure was proposed. In parallel, a chemical probe (DPBF) was used to characterize the formation of singlet molecular oxygen 1O2 during the period of m-THPC irradiation by MALDI-TOFMS. In both media (ethanol and aqueous), the m-THPC, the DPBF and their respective photoproducts were identified at once. Finally, to understand the photodegradation process in situ, our in vitro assays were performed directly on adherent cells on their culture support. The dye detection inside the whole cells was carried out by MALDI-TOFMS. HT29 human colon carcinoma cells were incubated with m-THPC (2µg/mL). After diode laser irradiation (652nm) of these cells, oxidized photoproducts and m-THPP traces were characterized in situ. Lastly, in an effort to generate proteomic data, three different cancerous cellular lines were analyzed. For each line, a specific protein fingerprint was achieved with reproducibility

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Garnier, Carole. "Segmentation de la prostate pour la thérapie par Ultrasons Haute Intensité guidée par l’Image." Rennes 1, 2009. https://tel.archives-ouvertes.fr/tel-00498035.

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Ce travail traite le problème de la segmentation d'images échographiques de prostate acquises en condition per-opératoire dans le cadre de la destruction de tumeurs effectuée par une technique d'ultrasons haute intensité (HIFU). L'objectif est de délimiter précisément les tissus cible de façon à concentrer l'échauffement induit par les ultrasons tout en réduisant leur impact sur les structures voisines. L' étude bibliographique de l'état de l'art montre que toutes les méthodes de segmentation se référant aux dernières avancées méthodologiques ont été tentées sans pour autant apporter de réponses complètement satisfaisantes au problème du fait de la variabilité des situations rencontrées et surtout de la qualité toute relative des images dans le cas des HIFU. Les différentes solutions proposées dans cette thèse s'appuient sur les modèles déformables discrets enrichis de recherche de points d'ancrage basés gradient, couplés ou pas à une approche de détection de surface optimale. Ces solutions sont testées sur une trentaine de bases de données et analysées à la fois qualitativement et quantitativement par comparaison à des contours définis par des experts. Par ailleurs, une étude préliminaire est conduite sur la caractérisation de texture par différents types de moments (Zernike, Legendre, etc. ). Les résultats obtenus montrent un comportement globalement correct et satisfaisant les temps de calcul imposés
This work deals with the segmentation of echographic prostate images acquired intra-operatively simultaneously to the application of high intensity ultrasound (HIFU) for the destruction of tumor. The objective is to precisely delineate the target in order to concentrate the heating induced by ultrasound and to reduce as much as possible their impact on the neighboring structures. After a brief presentation of the clinical and the technical context, in particular the dosimetry, a state-of-the-art is carried out: it shows that although all the most recent and effective methods have been explored, only partial solutions have been obtained due to a large variability of situations to deal with and the relatively poor quality of the images in HIFU devices. Several solutions are then proposed based on discrete deformable contours, improved by the search of gradient based landmark points, coupled or not with optimal search detection. These solutions are tested on about thirty datasets and qualitatively and quantitatively analysed by comparison with expert-defined contours. A preliminary study is also performed for texture characterization using different types of moments (Zernike, Legendre, etc. ). The results show that an overall good behaviour is obtained fulfilling the time computation constraints

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Castellví, Fernández Quim. "Non-focal non-thermal electrical methods for cancer treatment." Doctoral thesis, Universitat Pompeu Fabra, 2017. http://hdl.handle.net/10803/586217.

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Most physical ablation modalities for cancer treatment are focal and are based on thermal damage. Despite their regular clinical use as an alternative to surgical resection, their thermal principle of operation entails risks regarding the preservation of neighboring vital structures, such as large vessels, critical ducts or nerves. In addition, being focal, their use is unpractical in cases where multiple nodules are present or tumors are difficult to reach with the applicators. This thesis explores non-thermal electrical treatments which can be applied in a non-focal manner. Two treatments have been investigated: the first treatment, proposed by others a few years ago, is based on the permanent application of low magnitude alternating electric fields through surface electrodes. Here, this treatment has been in vivo studied to evaluate its efficacy as well as to discern whether it is non-thermally mediated. The second electrical treatment is based on the electroporation phenomenon and targets liver tumor nodules. Electroporation-based therapies employ brief high magnitude electric fields. These pulsed fields, alone or in combination with chemotherapeutic drugs, are able to kill cells by increasing their membrane permeability. Current electroporation-based therapies for internal tumors are local and are delivered through needle-shaped electrodes. Rather than using needle electrodes to treat liver tumors, here it is explored a novel treatment in which large plate electrodes are used to deliver the field across the whole liver in a non local fashion. The treatment aims at simultaneously destroying all tumors while preserving healthy tissue. Its efficacy is based on selectively enhancing the electric field over the tumors by infusing a solution with high electrical conductivity. The proposed treatment for liver tumors requires a high performance generator which is not currently available. The work presented here includes the design of a new generator topology able to fulfill the requirements.
La majoria del mètodes físics d'ablació tumoral es basen en produir dany tèrmic de manera focalitzada. Tot i ser considerats una alternativa habitual a la resecció quirúrgica, el principi tèrmic de funcionament, comporta un risc per la preservació d'estructures vitals adjacents a la zona de tractament, tals com grans vasos o nervis. A més, el fet de ser focals, fa impracticable la seva aplicació en cas de múltiples nòduls o tumors de difícil accés. Aquesta tesi explora tractaments elèctrics no basats en temperatura, capaços de ser aplicats de manera no focal. S'han investigat dos tractaments: El primer, proposat per altres fa pocs anys, està basat en aplicar permanentment camps elèctrics alterns de baixa magnitud a través d'elèctrodes superficials. Aquí, aquest tractament s'ha estudiat in vivo tant per avaluar la seva eficàcia com per discernir si aquesta resideix en la temperatura. El segon tractament es basa en el fenomen d'electroporació i persegueix el tractament de nòduls hepàtics. En els tractaments basats en electroporació, s’apliquen breus camps elèctrics de gran magnitud per tal de permeabilitzar la membrana cel·lular. Això permet la penetració d’agents quimioterapèutics o produeix directament la mort cel·lular. En lloc d'utilitzar, com és habitual, agulles per tal d'aplicar el tractament, aquí s'explora tractar tot el fetge de forma no localitzada, fent servir grans elèctrodes plans i paral·lels. Utilitzant solucions d'alta conductivitat elèctrica, es pretén magnificar selectivament el camp elèctric sobre els tumors, sent així capaços de destruir tots els tumors i alhora preservar el teixit sà. El tractament proposat per els tumors hepàtics, requereix d'un equip generador actualment no disponible. El presentat treball inclou el disseny d'una nova topologia de generadors capaç de complir amb els requisits.

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Hammarsten, Peter. "Androgen controlled regulatory systems in prostate cancer : potential new therapeutic targets and prognostic markers." Doctoral thesis, Umeå : Umeå University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1930.

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Ohlson, Nina. "Early effects of castration therapy in non-malignant and malignant prostate tissue." Doctoral thesis, Umeå : Univ, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-645.

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Johnson, Frank Phillip. "The impact of ablative facial cancer surgery and the affect of post-operative facial prostheses." Thesis, University of Sheffield, 2010. http://etheses.whiterose.ac.uk/12865/.

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This thesis examines psychosocial issues experienced by participants following a diagnosis of facial malignancy and ablative cancer surgery of the face. It investigates how participants felt about surgery and the affect that the use of postoperative facial prostheses had on each participant. Semi-structured interviews were used to capture participants' experiences of treatment. Interpretative Phenomenological Analysis (Smith 2004; Smith, Flowers & Larkin 2009) was used to perform a content analysis of the data which revealed themes and sub-themes common to all participants. Ethical approval was granted for the inclusion of up to eight participants in the study. Initially twenty participants were randomly selected and contacted by letter. Thirteen individuals agreed to their inclusion in the study and eight were randomly selected for inclusion and contacted by letter. The five individuals not selected were contacted and thanked. Interviewing ceased after the sixth participant had been interviewed n=6 after no new themes relative to the study were discovered. Some findings of the research were congruent with previous research. A supportive partner and family group make coping easier. Professional attendants who listen and allow individuals to talk have a positive impact. Findings specific to this study suggest that facial prostheses are useful after ablative cancer surgery of the face. Prostheses restore outward normality which was important for reasons of social acceptability. However, the study found that feelings of normality were not restored This concluded with a re-definition of normality for disfigured patients who use a facial prosthesis to incorporate the wider context revealed by the study.

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Chartier-Kastler, Emmanuel. "Ultrasons focalisés de haute intensité (U. F. H. I. ) : étude des effets celluaires et tissulaires de la pyrothérapie applications thérapeutiques et perspectives d'avenir en urologie." Paris 5, 1995. http://www.theses.fr/1995PA05CD03.

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Les Ultrasons Focalisés de Haute intensité (U. F. H. I. ) ont fait leur entrée dans l'arsenal thérapeutique chirurgical humain en phase clinique dans les années 1990. Ce procédé extracorporel de destruction physique des tissus par thermo- ou pyro-thérapie associe une technique de repérage de la cible tissulaire (échographie actuellement) et l'émission de trains d'ondes ultrasonores focalisés en un point de l'espace, pour produire une nécrose tissulaire irréversible, sans lésion des tissus traversés par le faisceau ultrasonore. En collaboration avec l'équipe de recherche et de développement d'une société déjà connue pour sa maîtrise des ultrasons focalisés (lithotripteurs, Edap-Technomed) nous avons participé à la mise au point du Pyrotech° et à l'évaluation de cette technique de chirurgie ultrasonore. La machine est constituée d'une coupelle hémisphérique sur laquelle sont disposées de multiples céramiques piézoélectriques (plusieurs têtes de tirs pour l'expérimentation), stimulées en phase à 1 MHz pour produire une tache focale de 2 x 10 mm à 32 cm. Le repérage est assuré par une sonde d'échographie centrale rétractable de 3,5 MHz et la transmission par un liquide de couplage anticavitation. Après un rappel de physique des sons, particulièrement centré sur les propriétés des ultrasons, nous nous intéresserons à plusieurs aspects fondamentaux de cette machine en vue de son utilisation humaine. Le principe physique a été vérifié in vitro sur fantômes de polyuréthane (270°c, 7 sec. De tir) et la précision du tir in vitro sur billes de PTX intravésicales (cochon). L'étape suivante fut de prouver la capacité de destruction cellulaire sur une lignée cellulaire tumorale vésicale d'origine humaine (647V) et de confirmer les capacités de destruction par atteinte de la vitalité cellulaire, des courbes de croissances et des capacités de clonage. In vivo ensuite travaillant sur le cochon (n>100) nous avons montrer la possibilité d'obtenir des lésions en profondeur sur la vessie, le foie et le rein, reproductible en site et en taille. Les analyses histologique des effets tissulaires et de leur cicatrisation ont été réalisés à JO, J7 et J90. Les phénomènes d'interfaces et d'échauffement cutané ont été analysés en terme de seuil d'apparition. Les températures atteintes au foyer étaient de 108°C en ¼ de seconde dans le rein. Aucune toxicité générale n'a été retrouvée chez 84 cochons de l'expérimentation (tension artérielle, rythme cardiaque, biologie sanguine) de même qu'aucun décès n'a été relevé. Les études de faisabilité pouvaient alors être initiées par l'homme. Les résultats expérimentaux ont été trouvés aussi bien histologiquement (rein sain ou tumoral, prostate, vessie) que sur le plan général ou pour les mesures de températures et de diffusion sur la prostate. L'adaptation de l'homme à la machine était contrôlée (lit, confort) et la technique de traitement des volumes testées (gestion informatique du déplacement spatiale). Il a été démontré que le principe des U. F. H. I. était efficace en terme d'atteinte tissulaire. Il restait à surmonter les problèmes rencontrés par la profondeur des tirs (qualité du repérage, effets de distorsion au foyer, choix de la puissance nécessaire et suffisante (atténuation), surveillance des interfaces, stratégie de tir des volumes). Nous discutons l'état actuel de la littérature sur l'ensemble de ces aspects, les autres équipes ayant toutes les mêmes résultats et se heurtant à des difficultés similaires. L'avenir en urologie des U. F. H. I. Dépendra des prochaines modifications en cours du Pyrotech° ou des autres machines et de l'affinement des indications pour chaque machine.

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Khokhlova, Mariya. "Interactions of cells with oxide thin films." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMC241.

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Dans le présent travail, nous montrons comment des couches minces d'oxydes peuvent être utilisées comme surfaces bioactives, un domaine de recherche encore peu exploré. À cet effet, des couches minces de TiO2, Al2O3, VOx et quelques autres oxydes ont été déposés sur des substrats de verre par la technique d'ablation laser pulsé (PLD), et l'adhésion, la prolifération et la différenciation de cellules souches mésenchymateuses humaines dérivées de moelle osseuse ont été évaluées. Le comportement des cellules a été analysé par rapport aux principaux paramètres de surface tels que la chimie, la mouillabilité, la morphologie et l'épaisseur des films. Nos résultats indiquent que les couches minces de TiO2 et Al2O3 peuvent non seulement favoriser l'adhésion et la croissance des cellules souches mésenchymateuses, mais peuvent également être utilisées pour influencer la différenciation ostéogénique et chondrogénique. En outre, l'effet de films minces d'oxydes sur l'adhésion et la croissance de lignées de cellules cancéreuses a été examiné. Nous avons montré que la culture de ces lignées cellulaires sur des films minces affecte leur croissance et, par conséquent, pourrait être une méthode utile pour effectuer des tests de dépistage des drogues.Cette étude fournira une meilleure compréhension de la corrélation entre la chimie de surface et la réponse cellulaire, qui a un role important dans le domaine de la fabrication de biomatériaux
In the present work we demonstrate how oxide thin films can be used as bioactive surfaces, a field of research which is still underexplored. For this purpose, thin films of TiO2, Al2O3, VOx and some others were deposited on glass substrates using the Pulsed Laser Deposition (PLD) technique, and adhesion, proliferation and differentiation of human bone marrow-derived mesenchymal stem cells were evaluated. Cell behavior was analyzed with respect to the various key surface parameters such as chemistry, wettability, morphology and the thickness of films.Our results indicate that thin films of TiO2 and Al2O3 can not only support mesenchymal stem cells adhesion and growth, but also can be used to influence osteogenic and chondrogenic differentiation path. Additionally, effect of oxide thin films on adhesion and growth of cancer cell lines was studied. We showed that culturing these cell lines on thin films affects their growth and, therefore, could be a valuable method to perform screening tests with drugs.This work will provide a better understanding of correlation between surface chemistry and cellular response, which has a high significance in the field of biomaterials fabrication

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Yang, Jian. "Design, synthesis, and evaluation of thiazolidinedione derivatives inhibiting Bcl-2/Bcl-xL or ablating androgen receptor in prostate cancer." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1243542151.

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Petrocelli, Diego. "Revisão Sistemática e Metanálise da Eficácia da Pesquisa de Corpo Inteiro pré-dose terapêutica com 131I em indivíduos com Carcinoma Diferenciado da Tireoide." Botucatu, 2018. http://hdl.handle.net/11449/155881.

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Orientador: Vania dos Santos Nunes Nogueira
Abstract: Although being controversial, some services use Whole Body Imaging (WBI) with 131I prior to the ablative dose with this radiopharmaceutical in the treatment of differentiated thyroid cancers (DTC). Proponents of this approach argue for a better optimization of the ablative dose, and opponents argue that this WBI could lead to the "stunning effect" characterized by reduced tissue uptake of 131I in ablative dose treatment, thereby compromising treatment and prognosis of these individuals. Objective: To evaluate whether WBI with 131I, ablative pre-dose, interferes with the efficacy of the therapeutic dose of iodine as remission of the disease after total or near total thyroidectomy in individuals with DTC. Methodology: A systematic review of the literature was conducted in which randomized, non-randomized and observational studies were included in which the patients were in the late postoperative period of total or subtotal thyroidectomy due to one of the DCT and were assigned the diagnostic WBI with I131 before the ablative dose (intervention) or they performed WBI with 123I before the ablative dose, or non-performance of the diagnostic WBI (directly ablative dose with 131I) (control). The primary outcome was disease remission assessed by the ablative success rate at least six months after follow-up. Results: After performing the searches in the following electronic databases Embase (1980-25/04/2017), Pubmed (1966-25/04/2017), CENTRAL (Cochrane Controlled Trials Register) (04/2... (Complete abstract click electronic access below)
Resumo: Apesar de existirem controvérsias, alguns serviços utilizam a pesquisa de corpo inteiro (PCI) com 131I previamente a dose terapêutica com esse radionuclídeo no tratamento dos cânceres diferenciados da tiroide (CDT). Os defensores dessa conduta argumentam uma melhor otimização da dose ablativa, e os contrários afirmam que essa PCI poderia ocasionar o “efeito stunning”, caracterizado pela redução da captação tecidual do 131I no tratamento com a dose ablativa, comprometendo com isso o tratamento e o prognóstico desses indivíduos. Objetivo: avaliar se a PCI com 131I, pré-dose ablativa, interfere na eficácia da dose terapêutica de iodo quanto a remissão da doença após a tireoidectomia total ou quase total em indivíduos com CDT. Metodologia: foi realizada uma revisão sistemática da literatura na qual foram incluídos estudos controlados randomizados, não randomizados e observacionais, nos quais os pacientes estavam em pós-operatório de tireoidectomia total ou subtotal devido um dos CDT, e foram alocados a um dos dois grupos: PCI diagnóstica com 131I realizada antes da dose terapêutica com I131(intervenção), ou a PCI realizada com 123I antes da dose ablativa, ou não realização da PCI diagnóstica antes da dose terapêutica (ambos controle). O desfecho principal foi a remissão da doença avaliada pela taxa de sucesso ablativo em pelo menos seis meses de seguimento. Resultados: depois de realizadas as pesquisas nas bases eletrônicas Embase (1980–25/04/2017), Pubmed (1966–25/04/2017), CENT... (Resumo completo, clicar acesso eletrônico abaixo)
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N'Djin, William Apoutou. "Transducteur torique à Ultrasons Focalisés de Haute Intensité pour générer des ablations volumineuses : applications précliniques pour le traitement des métastases hépatiques de cancers colorectaux." Lyon 1, 2008. http://www.theses.fr/2008LYO10313.

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Une sonde médicale peropératoire de thérapie ultrasonore dédiée à l’ablation thermique des métastases hépatiques de cancers colorectaux (MHCCR) a été développée et validée au stade préclinique sur le modèle porcin. L’objectif de ces travaux était de proposer un nouvel outil complémentaire à la résection chirurgicale. Un transducteur HIFU torique à imagerie intégrée a été mis au point pour générer des lésions volumineuses (7cm3, 40s). Les caractéristiques de ces lésions ont été étudiées en modélisation et lors d’essais précliniques in vivo. Des études de ciblage ont fait intervenir un modèle pseudotumoral implanté dans le foie. Ses caractéristiques acoustiques ont été validées comme compatibles avec l’ablation par HIFU. La stratégie thérapeutique mise en place (paramètre de tirs, approche peropératoire, guidage échographique) a permis de traiter les pseudotumeurs avec des marges négatives. Des ablations homogènes ont également été réalisées au contact de vaisseaux de 8 mm de diamètre dans des régions peu accessibles (confluent cavo-sus-hépatique). Puis, la sonde torique a été utilisée comme outil pour la résection chirurgicale assistée par HIFU (RA-HIFU). La RA-HIFU apporte des améliorations significatives en terme de contrôle vasculaire. Enfin, les effets des mouvements du foie in vivo sur les traitements HIFU ont été étudiés dans une méthode combinée de modélisation et d’images échographiques enregistrées sur animaux. Une étude in vivo a montré que le traitement HIFU réalisé avec la sonde torique était peu influencé par ce type de mouvements. Une étude clinique va être entreprise au Centre Léon Bérard en utilisant la stratégie de tir déterminée par ces travaux
An ultrasound therapeutic medical device dedicated for the thermal ablation of liver metastases from colorectal cancers (LMCC) during an open procedure was developed and validated at a preclinical stage in a pig model. The aim of this study was to propose a HIFU device complementary to surgical liver resection. A toroïdial-shaped HIFU transducer with integrated ultrasound imaging was developed for creating large single lesions (7cm3, 40s). The characteristics of these lesions were studied numerically, during in vivo preclinical evaluations. Ballistic studies introduced a model of tumor-mimic embedded in the liver. Its acoustical characteristics were found to be adequate for HIFU ablation. The therapeutic strategy (open procedure, HIFU exposures parameters, ultrasound guidance) allowed the treatment of the tumor-mimics with negative margins. Homogeneous ablations were also performed in the vicinity of vessels up to 8 mm in diameter in less accessible regions (cavo-hepatic junction). Then, the toroïdial-shaped HIFU device was used for assisting surgical resection. The method enhances significantly vascular control during resection. Finally, in vivo liver motion effects on HIFU treatments were studied in a combined method included modeling and acquisition of preclinical ultrasound images in animals. An in vivo study has demonstrated that using this HIFU device during an open procedure allows creating ablations that are identical to those created during apnea. On the basis of these results, a clinical study will be started at the cancer center Léon Bérard with the toroïdial-shaped HIFU medical system by using the HIFU exposure strategy determined in this work

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Huang, Jui-Wen. "Part 1: Troglitazone analogues as cyclin D1 ablative agents: the potential drugs for breast cancer therapy Part 2: Vitamin E and its analogues induce apoptosis in prostate cancer cells in part through inhibition of Bcl-2/Bcl-XL functions /." Columbus, Ohio : Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1128050561.

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Baloche, Valentin. "Contributions négatives et positives de la galectine-9 au développement tumoral : étude dans des modèles tumoraux murins syngéniques In the MB49 Murine Model, Genetic Ablation of Galectin-9 Enhances Anti-Tumor Immune Response: Possible Role of a Greater CXCL9/Il-6 Production Tumor Exosomal Micrornas Thwarting Anti-Tumor Immune Responses in Nasopharyngeal Carcinomas Interferon β and Anti-PD1/PD-L1 Checkpoint Blockade Cooperate in NK Cell-Mediated Killing of Nasopharyngeal Carcinoma Cells Interferon Beta Increases NK Cell Cytotoxicity against Tumor Cells in Patients with Nasopharyngeal Carcinoma via Tumor Necrosis Factor Apoptosis-Inducing Ligand Emerging Therapeutic Targets for Nasopharyngeal Carcinoma: Opportunities and Challenges Galectin-9 Promotes a Suppressive Microenvironment in Human Cancer by Enhancing STING Degradation." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASS117.

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Comme les autres galectines, la galectine-9(gal-9) est une lectine animale qui interagit avec un sous-groupe défini de polysaccharides portés par des glycoprotéines ou des glycolipides. La gal-9 associée aux cellules exerce de multiples fonctions dans le cytoplasme, dans le noyau et à la surface de la membrane plasmique. Quelques publications suggèrent que la gal-9 intra-cellulaire inhibe la mobilité des cellules malignes et exerce un effet antimétastatique. En outre la gal-9 peut être sécrétée dans le milieu extra-cellulaire où elle se comporte comme une cytokine avec des effets principalement immunosuppresseurs. Ces effets ont été mis en évidence dans un contexte tumoral chez l’homme et dans des modèles murins. Cependant, on ne disposait pas jusqu’à présent d’un modèle tumoral murin permettant d’évaluer les effets pro-tumoraux ou antitumoraux de la gal-9 indépendamment de la gal-9 des cellules infiltrantes. Pour résoudre ce problème, nous avons dérivé, en employant la technologie CRISPR/Cas9, des clones isogéniques invalidés ou non pour la gal-9 à partir de 2 lignées tumorales murines : CT26 (fond génétique BALB/c) et MB49 (fond génétique C57BL/6). Dans le cas de la lignée MB49, nous avons pu mettre en évidence un phénotype remarquable in vivo. Lors de transplantations itératives, on assiste pour les tumeurs dérivées des clones invalidées à une réduction drastique de la croissance tumorale au bout de 3 ou 4 passages sur les souris syngéniques mais pas sur les souris immunodéficientes. L’émergence de la réponse immunitaire responsable de cet arrêt de la croissance tumorale a été étudiée par immunohistochimie, dosage de cytokines en multiplex dans les extraits tumoraux et analyse du transtriptome par RNAseq. L’augmentation de la production intra-tumorale d’interféron-γ, de CXCL9 et d’Il-6 semble jouer un rôle important dans le renforcement de la réponse immunitaire contre les tumeurs KO-gal-9
Like other galectins, galectin-9 (gal-9) is an animal lectin which interacts with a defined subgroup of glycans carried by glycoproteins or glycolipids. Gal-9 associated with cells performs multiple functions in the cytoplasm, in the nucleus and at the surface of the plasma membrane. Some publications suggest that intracellular gal-9 inhibits the mobility of malignant cells and exerts an anti-metastatic effect. In addition, gal-9 can be secreted into the extracellular medium where it behaves like a cytokine with mainly immunosuppressive effects. These effects have been demonstrated in the context of human tumors and in mouse tumor models. However, so far there was no murine tumor model available to assess the pro-tumor or anti-tumor effet of gal-9 independently of gal-9 produced by infiltrating cells. To address this issue, we derived isogenic clones invalidated or not for gal-9 from 2 murine tumoral lines : CT26 (BABL/c genetic background) and MB49 (C57BL/6 genetic background), using CRISPR/Cas9 technology. In the case of the MB49 line, we were able to demonstrate a remarkable phenotype in vivo. During serial transplantations, we saw, for tumors derived from invalidated clones, a dramatic reduction in tumor growth after 3 or 4 passages in syngenic mice but not in immunodeficient mice. The emergence of the immune response responsible for this arrest of tumor growth was investigated by immunohistochemistry, multiplex cytokine assay in tumor extracts and transcriptome analysis by RNAseq. Increased intra-tumor production of interferon-γ, CXCL9 and Il-6 appears to play an important role in enhancing the immune response against KO-gal-9 tumors

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Revollo, Barriga Boris Teófilo. "Efectividad de un programa de cribado, basado en la citología anal, anoscopia de alta resolución y tratamiento ablativo, como estrategia para prevenir el cáncer anal invasivo en personas infectadas por el virus de la inmunodeficiencia humana." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/669844.

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El carcinoma escamo celular anal invasivo es un cáncer muy raro en la población general, pero muy frecuente los pacientes infectados por el VIH, principalmente los Hombres que tienen Sexo con Hombres, aunque los Hombres que tienen sexo con Mujeres y las mujeres infectadas por el VIH tienen también un riesgo mucho más alto que la población general. Actualmente no existe evidencia sobre la eficacia de las distintas estrategias empleadas para detectar y tratar las displasias anales de alto grado, que potencialmente pueden avanzar a un carcinoma escamo celular anal invasivo. El propósito de la presente tesis es demostrar la efectividad de un programa de cribado de displasia anal basada en la realización de citologías anales y anoscopia de alta resolución como estrategia de cribado de las displasias anales de alto grado, con el fin de prevenir el carcinoma escamo celular anal invasivo.
Invasive anal squamous-cell carcinoma is a rare cancer in the general population, but common in HIV-infected patients, especially in Men who have Sex with Men, although Men who have sex with Women and women infected with HIV they also have a much higher risk than the general population. There is currently no evidence on the efficacy of the different strategies used to detect and treat high-grade anal dysplasia, which can potentially advance to an invasive squamous cell carcinoma. The purpose of this thesis is to demonstrate the effectiveness of an anal dysplasia screening program based of anal cytology and high resolution anoscopy to prevent nvasive anal squamous-cell carcinoma.

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Lowery, Amanda Raley. "Nanoshell-assisted cancer therapy: Targeted photothermal tumor ablation." Thesis, 2007. http://hdl.handle.net/1911/20625.

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This thesis details the development of a targeted nanoshell therapy for cancer specific photothermal ablation. By attaching targeting antibodies or ligands to the nanoshell surface, these targeted nanoshells preferentially bind to tumor sites. When NIR light is applied over the tumor region containing nanoshells, the nanoshells heat, thus destroying the tumor. The targeted nanoshells therapy is demonstrated here in vitro and in vivo, targeting both the cancer cells and the angiogenic vasculature. In vitro, anti-HER2 antibody was used to bind nanoshells directly to the cancer cells, which express HER2. The cancer vasculature was targeted in vitro and in vivo by vascular endothelial growth factor (VEGF), which binds to the VEGF receptor on endothelial cells. Nanoshells targeted against cancer cells were conjugated with anti-HER2 antibodies to facilitate the binding on nanoshells to SKBR-3 breast cancer cells. Upon NIR excitation, the nanoshell-laden cells were thermally ablated. Both membrane-bound nanoshells and NIR laser irradiation are required simultaneously to destroy the cancer cells. Cells incubated with targeted nanoshells without laser irradiation continued to be viable. When healthy cells and cancerous cells were co-cultured, cancer cells could still be targeted and ablated without damaging the adjacent healthy cells. Similar to anti-HER2 nanoshells binding cancer cells, nanoshells conjugated with the soluble VEGF bound vascular endothelial growth factor receptors on endothelial cells. Selectively killing endothelial cells removes the blood supply sustaining the tumor and demonstrates the feasibility of targeted nanoshells as an anti-angiogenic strategy. VEGF nanoshells incubated with endothelial cells in vitro produced a circular area of cell death after laser irradiation. A tumor-bearing mouse model further validated the vascular targeting when VEGF nanoshells induced tumor regression after systemic nanoshell delivery and laser irradiation. Both in vivo and in vitro studies confirmed the ability to selectively induce cell death with the photothermal interaction of immunonanoshells and NIR light. Immunonanoshells exposed to laser irradiation produced targeted cell death of cancer cells even when cancer cells were in close proximity to normal healthy cells. Immunonanoshells are a promising minimally invasive cancer therapy due to their biocompatibility, selective cell specific binding, and NIR-assisted photothermal destruction of tumor tissue.

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48

Lin, Hsiao-Ling, and 林筱玲. "Develpoment of Focused Ultrasound Transducer for Prostate Cancer Ablation." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/598and.

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碩士
國立臺灣大學
醫學工程學研究所
106
Ultrasound has a good ability to penetrate soft tissue. High-intensity focused ultrasound (HIFU) transducers are capable of concentrating acoustic power to generate a steep temperature elevation in the focal zone, causing thermally coagulative necrosis of tumor. The purpose of this work was to develop HIFU transducers dedicated for the non-invasive treatment of prostate cancer. Transducers with elliptic or rectangular aperture were designed in this study. Acoustic fields of transducers were calculated based on Rayleigh-Sommerfeld Diffraction Integral and the size of focal zone was analyzed. MATLAB 2017a (The MathWorks, Inc., Natick, MA) was used in the numerical simulation. The initial design of the transducer was 22 mm in width and 45 mm in height, a radius of curvature of 45 mm, and the center frequency of 3.5 MHz. The transducers were made of 1-3 piezoelectric composites, where PZT 8 was the active material and epoxy was the passive material. The center frequency of the transducer prototype was 3.8 MHz with the -6 dB bandwidth of 0.45 MHz. Moreover, the electro-acoustic efficiency and focal zone were measured to be 12.45% and 2x1.6x4.2 mm3. Experimental results of ablating thermo-sensitive phantoms verified the feasibility of the developed transducer.

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49

Price, Jacqueline. "Microwave ablation therapy for colorectal liver metastases." Thesis, 2016. https://hdl.handle.net/2144/19441.

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BACKGROUND: The gold standard treatment for colorectal cancer liver metastases (CRCLM) is surgical resection. Unfortunately, the majority of patients with colorectal hepatic metastases are not candidates for resection. In recent years, several alternatives have emerged for patients whom are not resection candidates including modern systemic chemotherapy, targeted biologic treatments, regional therapies and local tumor ablation options. Microwave ablation (MWA) therapy is one such treatment alternative, based on thermal tissue ablation. This modality in concert with the most recent published literature on its use for patients with CRCLM will be reviewed in this paper. LITERATURE REVIEW FINDINGS: A structured review of the literature on ablative technologies was performed. In recent years, there has been an evolution from radiofrequency ablation (RFA) to microwave ablation therapy for the treatment of CRCLM. RFA has several limitations to its use and MWA theoretically avoids such limitations making it the currently preferable treatment option. There are limited publications comparing the use of RFA to MWA and limited publications on the use of microwave ablation for CRCLM. This paper will focus on the most recent data on MWA for CRCLM. This data can then be compared to the already published data on RFA. PROPOSED METHODS: Given the relative novel status for MWA as a treatment option for CRCLM, a potential disadvantage for its use is the perceived lack of knowledge across the medical professional spectrum. In an effort to expand the knowledge of MWA, the proposed outcomes for this study include creating a curriculum to be offered as a CME course focused for Primary Care Providers (PCPs) to provide a basis of clinical familiarity for its use. This effort will familiarize providers who may have patients diagnosed with CRCLM and also allow them to initiate the conversation about this therapy with their patients who may be candidates for this treatment. CONCLUSIONS: MWA therapy is a safe and effective treatment modality for CRCLM. Due to this new development in treating liver lesions originating from colorectal cancer, it’s imperative for providers to become familiar with these new technologies especially considering the high incidence of CRCLM. Therefore, a curriculum for PCPs will allow for a better understanding of this new technology and foster better provider-patient relationships.

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50

Jian-WeiLiang and 梁建緯. "Mesoporous SiO2 Templated CuS Nanoparticles With Potential Application In Laser Ablation of Cancer Cells." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/68949641355482344323.

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