Дисертації з теми "Immunothérapie anticancéreuse – Effets secondaires"
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Capuron, Lucile. "Évaluation des effets psychotropes des cytokines utilisées en thérapeutique anticancéreuse : un modèle d'étude des relations entre le système immunitaire et le système nerveux central." Bordeaux 2, 1999. http://www.theses.fr/1999BOR21026.
Повний текст джерелаL'Orphelin, Jean-Matthieu. "Ρarticularité cliniques et impacts thérapeutiques des effets indésirables immunο-induits chez les patients atteints d'un mélanοme de stade ΙV". Electronic Thesis or Diss., Normandie, 2024. http://www.theses.fr/2024NORMC406.
Повний текст джерелаBackground. Immune checkpoint inhibitors are the undisputed first-line treatment for stage IV melanoma, and are associated with adverse events, often immuno-related. Immune-related events are increasingly taken into account in therapeutic decisions, and there is a desire to individualize the management of patients with metastatic melanoma. A more detailed characterization of these events would enable better prediction of their occurrence and impact. Our knowledge of immuno-related events comes mainly from randomized phase III clinical trials, through the collection of safety data for the duration of the study. This does not allow us to identify late-onset safety signals, occurring long after the clinical trial, or rare safety signals not always reported in the publication. . Materials and methods. A safety meta-analysis conducted on randomized clinical trials from ClinicalTrials.gov aims to identify rare safety signals allowing greater comprehensiveness. We determined the type and incidence of rare events (represented by cardiovascular events) associated with exposure to immune checkpoint inhibitors in stage IV melanoma. Post-marketing studies have been carried out on three databases: RIC-Mel and Vigibase®, set up beforehand, and Melskintox, specifically set up to record cutaneous immune-related effects. These “real-life” studies make it possible to investigate the type, incidence and impact of dermatological immune-related events at risk of under-reporting, and to characterize all late-onset immune-related events late after the introduction of the immune checkpoint inhibitor, since follow-up from randomized clinical trials is too short to be informative. Finally, we discussed the safety of reintroducing an immune checkpoint inhibitor after an immuno-related event. Results. The meta-analysis enables us to identify some immuno-related events not initially identified in randomized clinical trials because they are rare and not systematically investigated, such as cardiovascular events. However, they can be serious as myocarditis and pericarditis. Some, such as dyslipidemia, suggest a long delay in onset, made possible by the extended overall survival of melanoma patients treated with immune checkpoint inhibitors. In real-life cohort studies, other severe late-onset events may occur long after from the initiation of treatment (after two years), affecting all organs. Patients with SSM melanoma appear to have a higher risk of late-onset adverse events. Certain frequent and rare serious immune-related events are imperfectly investigated, and the diversity of clinical presentations is poorly understood. The prognosis seems to differ depending on whether the cutaneous immuno-related effect is a benign inflammatory dermatosis, a pigmentary disorder, drug-related rash or bullous dermatosis. Finally, pharmacovigilance data on reintroduction vary according to the initial immune-related event, suggesting a higher recurrence rate for nephritis and cutaneous immuno-related events. Discussion and perspectivesThe occurrence of an immune-related event must be known and recognized with regard to its therapeutic impact, and be the subject of appropriate monitoring modalities. A more detailed knowledge of safety data and a better characterization of immune-related events will enable us to tailor our treatment pathways and proposals
Al-Sakere, Bassim. "L'électrochimiothérapie antitumorale : Optimisation des effets locaux et systémiques." Paris 11, 2009. http://www.theses.fr/2009PA11T035.
Повний текст джерелаNawrocki, Laurent. "Chimiothérapie anticancéreuse et croissance dentaire." Lille 2, 1999. http://www.theses.fr/1999LIL2D002.
Повний текст джерелаFerraro-Peyret, Carole. "Induction d'apoptose des lymphocytes T par des molécules utilisées en chimiothérapie anticancéreuse : mécanismes, conséquences." Lyon 1, 2001. http://www.theses.fr/2001LYO1T253.
Повний текст джерелаMartin, Ingrid. "La chimiothérapie anticancéreuse chez l'enfant : complications, prévention et traitement." Paris 5, 1994. http://www.theses.fr/1994PA05P051.
Повний текст джерелаGiraud, Véronique. "Étude des effets dépressogènes des immunothérapies chez des patients atteints de cancers du rein métastatiques : rôle de certains facteurs psychologiques, biologiques et sociaux : une recherche exploratoire en psychologie de la santé." Bordeaux 2, 2004. http://www.theses.fr/2004BOR21100.
Повний текст джерелаThe diagnosis of renal cell carcinoma and the treatment associated, are highly stressful events in the life of a man or a moman. Nowadays, neoplasm is one of the first cause of mortality in France. During the last twenty years, psychoneuroimmunology has demonstrated an intricate network of bidirectional relationships between the immune system and the brain. Cytokines that are released by immune cells during the host response to infection, represent the main mediators of the communication between the immune system and the central nervous system. By their potent immunomodulatory effects, cytokines are used for the treatment of several forms of cancers. However, cytokines therapies are often accompanied by several side effects that impair the patient's quality of life, and limit the continuation of immunotherapy. Psychiatric disturbance that occur during cytokine treatment are undefined and impredictable. The principal objectives of our study are, in one hand, to show that subjects are differencied by psychosocial factor and transaction, and in the other hand, to identify a cognitive comportemental specific pattern, for cancerous patients at the beginning of immunotherapy. The study was carried out on patients suffering from metastatic renal cell carcinoma and receiving cytokine immunotherapy, (Institut Bergonié and CHU of Bordeaux) with the Health Psychology model Study of Bruchon-Schweitzer and Dantzer (1994). The main results show that cytokine therapy is accompanied by depressive symptoms. As soon as the first and second week of immunotherapy, patients treated display depressive symptomatology
Delaunay, Tiphaine. "Etude de différents virus oncolytique pour l'immunothérapie du cancer : mécanisme de la sensibilité tumorale et effets sur la réponse immunitaire." Thesis, Nantes, 2018. http://www.theses.fr/2018NANT1020/document.
Повний текст джерелаOncolytic immunotherapy exploits the lytic and immunogenic properties of oncolytic viruses (OV). These viruses selectively replicate in and lyze tumor cells without harming healthy tissues. During my thesis, I first identified the bi-allelic deletion of genes encoding type I interferons (IFN I, IFN-α et -β) as the most frequent defect in the IFN I antiviral response in malignant pleural mesothelioma (MPM). These alterations make the tumor cells permissive to attenuated oncolytic measles virus that subsequently provokes their lysis. I also showed that this loss of IFN I genes is common to cancers for which the deletion of the tumor suppressor gene CDKN2A is critical (glioblastoma, esophageal cancer). This is the first report showing a link between the deletion of IFN I genes and the sensitivity of tumor cells to OV. This link could be used as a predictive marker of the efficacy of oncolytic immunotherapy. I then demonstrated in vitro and in vivo a strong oncolytic activity against MPM of the VVTK-RR- modified vaccinia virus deleted from the genes encoding the thymidine kinase and the ribonucleotide reductase. This OV is thus of particular interest for oncolytic immunotherapy of MPM. Finally, I demonstrated a new mechanism by which different OV favor the human anti-tumor immune response. By lyzing tumor cells, OV allow the intercellular transfer of tumorassociated antigens such as NY-ESO-1 and induce or reinforce the presentation of these antigens to specific cytotoxic CD4+ T cells. Overall, my PhD work provides a better understanding of both the oncolytic activity of different viruses and their effects on the antitumor immune response
Bouvier, Emmanuel. "Conception, synthèse et évaluations biologiques de prodrogues du paclitaxel et du docetaxel activées par voie enzymatique dans le cadre des stratégies de chimiothérapie anticancéreuse ADEPT et PMT." Paris 5, 2003. http://www.theses.fr/2003PA05P623.
Повний текст джерелаPaclitaxel (Taxol®) and its semisynthetic analogue docetaxel (Taxotere®) belong to a family of efficient antitumor drugs and have been approved for the treatment of various cancers (ovarian, breast, lung). Their clinical use brings about severe side-effects due to their innate toxicity and formulation. Their transformation in less cytotoxic and more hydrophylic prodrugs is a way to improve their clinical use. Moreover a selective delivery to tumors in PMT or ADEPT strategies is then possible. To reach this goal, some glucuronylated paclitaxel and docetaxel prodrugs with a double spacer (p-hydroxybenzyl linked to a diamine tether by means of a carbamate) have been synthesized. This approach was shown efficient by the good results of the biological studies (stability, cytotoxicity, enzymatic hydrolysis). The conception and the synthesis of spacers useful for the preparation of other prodrugs are also presented
Faibis, Didier. "Les accidents d'hypersensibilité liés aux médicaments antimitotiques." Paris 5, 1991. http://www.theses.fr/1991PA05P048.
Повний текст джерелаFontas, Eric. "Tolérance et efficacité du traitement par Interleukine-2 chez les patients infectés par le virus de l’immunodéficience humaine : une approche observationnelle." Paris 6, 2010. http://www.theses.fr/2010PA066570.
Повний текст джерелаCophignon, Auréa. "Transport ionique dans les neuropathies périphériques induites par les agents anticancéreux : compréhension et atténuation des effets secondaires induits par la chimiothérapie cytotoxique." Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2018. http://www.theses.fr/2018AZUR4051.
Повний текст джерелаPlatinum-based drugs (cisplatin, oxaliplatin and carboplatin) and taxanes (paclitaxel and docetaxel) are among the most common drugs families used in chemotherapy. They are used for treatment of numerous human cancers including bladder, breast, head and neck, lung, ovarian, prostate and testicular cancers. However, these anticancer drugs cause significant peripheral neuropathies, that can become irreversible and leave serious clinical sequelae in patients. These include tinnitus, dizziness, tingling, numbness, loss of sensitivity, allodynia to touch or temperature changes and hyperalgesia. These side effects are highly restrictive and significantly reduce the quality of life of 30-50% of patients. The clinical significance is considerable, since it leads to about one-third of patients with stopping and/or changing treatments, although these are effective on tumors.Platinum-based drugs are DNA binding agents: they generate DNA lesions on the purine bases of DNA, that will be recognized by DNA damage response proteins, leading to cell death. Taxanes block the cell cycle in mitosis, by stabilizing the microtubule cytoskeleton against depolymerization. The fact that these two completely different antitumor mechanisms of action, induce the same peripheral neuropathies in the short to medium term, is paradoxical and has no explanation.The aim of my PhD research project was to study the mechanism(s) behind these neuropathies and to develop a new formulation to prevent and/or reduce them. Therefore, I studied the effects of taxanes and platinum-based drugs on several ion channels, involved in nociception. These ion channels, called nociceptors, are transcribed into the cell bodies of dorsal root ganglia (DRGs) and located to the peripheral nerve endings. They detect mechanical, thermal and chemical stimuli and generate or transmit the corresponding action potentials. Changes in gene expression and/or activity of nociceptors, will therefore modify the nociceptive thresholds and the transmission of different stimuli.My results allowed me to quantify, in primary cell culture of mouse DRGs and in vivo, the remodeling of ion channel expression induced by chemotherapy, in correlation with the development of peripheral neuropathies, that I measured by behavioral assessment. These results allowed us to identify a family of candidate molecules, that could potentially counteract the mechanism identified in this work. I showed that one of these molecules, can restore the gene expression of nociceptors and suppress peripheral neuropathies in mice. This work should continue as part of a valorization process, aiming to lead to a preventive and/or curative treatment, of these neuropathies in patients
Brunel, Simon. "Immunothérapie du cancer par administration d’anticorps monoclonaux anti-HVEM ou anti-ICOS chez la souris humanisée : potentiel thérapeutique et effets immunologiques." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066215.
Повний текст джерелаA new pair of co-signaling receptors (BTLA / HVEM) has recently been proposed as an important actor in tumor escapement. HVEM expression has been identified in wild type of cancers. Its expression level is inversely correlated with patient survival. Expression of HVEM by tumor cells could inhibit the immune response through BTLA expressed by T lymphocytes.Thus, in our work, monoclonal antibodies (mAb) targeting HVEM were evaluated in a model of NSG mice grafted with human T cells and tumors. We first characterized an anti-HVEM clone with high affinity in vitro. The clone selected for our study showed its ability to promote activation of human T lymphocytes in vivo as evidenced by worsening symptoms and mortality associated with human PBMC transfer in mice. The anti-tumor effect observed in the absence of adoptive transfer was enhanced in the presence of T lymphocytes, suggesting an additive effect of the antibody on the tumor and T lymphocytes. A decrease in regulatory T lymphocytes and an increase in the proliferation of CD8 + T lymphocytes in the tumor was sometimes associated with this growth retardation.By reproducing a partially human environment in NSG mice, we were able to evaluate the therapeutic effect of an anti-HVEM mAb in the development of two types of human tumors and its impact on the human immune system. Our results indicate that HVEM, by its expression by the tumor and the T lymphocytes, could be a judicious track for the immunotherapy of the cancer
Khelifi, Ilhem. "Conception, synthèse et évaluation de nouveaux composés hétérocycliques analogues de l'isoCombrétastatine A-4 : vers des composés antivasculaires à effets secondaires amoindris." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS280.
Повний текст джерелаCombretastatin A-4 (CA-4), is a natural antivascular agent isolated from a South African Sallow tree that selectively destroys tumor vasculature leading to ischemic necrosis. In 2016, the prodrug fosbretabulin (CA-4P) obtained designation as orphan drug in USA and Europe for the treatment of neuroendocrine tumors and glioblastoma. Despite its importance as a therapeutic agent, fosbretabulin has shown chemical instability. In fact, the double bond form Z isomerizes to an inactive E form of the drug. Moreover, fosbretabulin is associated to several side-effects including cardiotoxicity. Our group succeeded in the design of a more stable and non-isomerizable form of CA-4 as isoCA-4 which exhibited similar biological activities as CA-4. It was thought that cardiotoxicity of CA-4 and analogs is probably due to the presence of the 3,4,5-trimethoxyphenyl A-ring however the latter seems to have an essential role for the cytotoxic and antitubulin activities of the drug. Despite the role of the trimethoxyphenyl ring, we have focused our challenges on the remplacement of this moiety by various heterocycles to reduce the cardiotoxicity and to put an end to this dogma. We have identified three new classes of heterocyclic and bis-heterocyclic antivascular agents. We have demonstrated that these "drug-like" molecules have excellent antiproliferative activities at nanomolar ranges, an antivascular activity superior to that of CA-4 and possesses a very high cardiac safety index. Regarding these results, we have been able to show for the first time that the replacement of the 3,4,5-trimethoxyphenyl ring of isoCA-4 by various heterocyclic systems is a promising approach to synthesize new antivascular agents having a low level of cardiotoxicity
Cophignon, Auréa. "Transport ionique dans les neuropathies périphériques induites par les agents anticancéreux : compréhension et atténuation des effets secondaires induits par la chimiothérapie cytotoxique." Thesis, Université Côte d'Azur (ComUE), 2018. http://www.theses.fr/2018AZUR4051.
Повний текст джерелаPlatinum-based drugs (cisplatin, oxaliplatin and carboplatin) and taxanes (paclitaxel and docetaxel) are among the most common drugs families used in chemotherapy. They are used for treatment of numerous human cancers including bladder, breast, head and neck, lung, ovarian, prostate and testicular cancers. However, these anticancer drugs cause significant peripheral neuropathies, that can become irreversible and leave serious clinical sequelae in patients. These include tinnitus, dizziness, tingling, numbness, loss of sensitivity, allodynia to touch or temperature changes and hyperalgesia. These side effects are highly restrictive and significantly reduce the quality of life of 30-50% of patients. The clinical significance is considerable, since it leads to about one-third of patients with stopping and/or changing treatments, although these are effective on tumors.Platinum-based drugs are DNA binding agents: they generate DNA lesions on the purine bases of DNA, that will be recognized by DNA damage response proteins, leading to cell death. Taxanes block the cell cycle in mitosis, by stabilizing the microtubule cytoskeleton against depolymerization. The fact that these two completely different antitumor mechanisms of action, induce the same peripheral neuropathies in the short to medium term, is paradoxical and has no explanation.The aim of my PhD research project was to study the mechanism(s) behind these neuropathies and to develop a new formulation to prevent and/or reduce them. Therefore, I studied the effects of taxanes and platinum-based drugs on several ion channels, involved in nociception. These ion channels, called nociceptors, are transcribed into the cell bodies of dorsal root ganglia (DRGs) and located to the peripheral nerve endings. They detect mechanical, thermal and chemical stimuli and generate or transmit the corresponding action potentials. Changes in gene expression and/or activity of nociceptors, will therefore modify the nociceptive thresholds and the transmission of different stimuli.My results allowed me to quantify, in primary cell culture of mouse DRGs and in vivo, the remodeling of ion channel expression induced by chemotherapy, in correlation with the development of peripheral neuropathies, that I measured by behavioral assessment. These results allowed us to identify a family of candidate molecules, that could potentially counteract the mechanism identified in this work. I showed that one of these molecules, can restore the gene expression of nociceptors and suppress peripheral neuropathies in mice. This work should continue as part of a valorization process, aiming to lead to a preventive and/or curative treatment, of these neuropathies in patients
Auroy, Catherine. "Dysfonctionnements thyroi͏̈diens chez des patients atteints de mélanome malin et traités par chimioimmunothérapie." Paris 5, 1994. http://www.theses.fr/1994PA05P258.
Повний текст джерелаBouchenaki, Hichem. "Evaluation de l'effet de molécules candidates dans des modèles murins de neuropathies périphériques induites par la chimiothérapie anticancéreuse." Thesis, Limoges, 2020. http://www.theses.fr/2020LIMO0035.
Повний текст джерелаChemotherapy-induced peripheral neuropathies (CIPN) are a common side effets of chemotherapeuticagents. CIPN symptoms are mainly sensitive: pain, tingling, numbness or alterations of thermal andtactile sensitivity. CIPN symptomatology is associated to decreased patient quality of life and can leadto decreased chemotherapy doses and cycles, or even therapy cessation. Current CIPN managementconsists in the administration of medications recommended in the treatment of neuropathic pain, withvery low efficacy. The benefit of using renin-angiotensin system modulators has been previouslydemonstrated in our lab, in a murine model of vincristine-induced peripheral neuropathy. In thepresent work, we developed a new model of neuropathic pain, induced by oxaliplatin (OXP), achemotherapeutic agent belonging to the platinum family. We showed that an angiotensin-convertingenzyme inhibitor, ramipril, was able to alleviate OXP-induced neuropathic pain. We also showed thatboth ramipril and candesartan, an angiotensin II AT1 receptor antagonist, were able to prevent tactileallodynia induced by paclitaxel (PTX), a chemotherapeutic agent belonging to the taxane family. Thepreventive effect of candesartan against PTX-induced tactile allodynia is mediated by the indirectstimulation of angiotensin II AT2 receptors. Paradoxically, the direct or indirect AT2 receptorsstimulation did not prevent OXP-induced neuropathic pain, thus highlighting the necessity to adapt thepotential CIPN treatments to each chemotherapeutic agent physiopathology
Dolly, Adeline. "Cachexie cancéreuse : composition corporelle, structure et métabolisme du muscle squelettique." Thesis, Tours, 2019. http://www.theses.fr/2019TOUR3808.
Повний текст джерелаCancer cachexia is a multifactorial syndrome characterized by progressive loss of skeletal muscle, leading to decreased quality of life, response to cancer treatments, and patient survival. Due to the physio pathological complexity of this clinical syndrome, there is currently no cure to cancer cachexia.Despite recent discoveries, the mechanisms underlying skeletal muscle wasting are not clearly understood. Recent preclinical and clinical studies highlighted possible alterations in mitochondrial and lipid metabolism. Furthermore, body composition could be affected not only by the tumor, but also by anti-cancer treatments.During this PhD, the aims were to study the links between body composition and bevacizumab-based chemotherapy treatment (clinical study STIC-Avastin (NCT00489697)); or with skeletal muscle structure and metabolism, in the context of cancer cachexia (clinical protocols METERMUCADIG (NCT02573974) and METERMUS-IMC (NCT03027479))