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Levy, Karine. "Toxicité du cyclophosphamide". Paris 5, 1993. http://www.theses.fr/1993PA05P156.
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Afsharian, Parvaneh. "Optimization of cyclophosphamide therapy based on pharmacogenetics /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-997-1/.
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Yule, S. M. "The clinical pharmacology of cyclophosphamide in children". Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309831.
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Chanellière, Christiane. "Intérêt de l'utilisation du cyclophosphamide dans le traitement des pemphigoi͏̈des bulleuses et des pemphigus". Montpellier 1, 1989. http://www.theses.fr/1989MON11064.
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Belfayol-Pisanté, Laurence. "Evaluation d'un index prédictif de l'apparition des effets secondaires liés au traitement par le cyclophosphamide chez des patients atteints de vascularites et de collagénoses". Paris 5, 2000. http://www.theses.fr/2000PA05P629.
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Le cyclophosphamide est un agent anticancéreux et immunosuppresseur utilisé aussi bien dans le traitement des affections malignes que des maladies systémiques. Si les études pharmacocinétiques ont été largement décrites chez les patients traités par le cyclophosphamide seul ou en association pour ses propriétés antinéoplasiques, aucune n'aborde la pharmacocinétique du cyclophosphamide et de son métabolite, le 4-hydroxycyclophosphamide/aldophosphamide, chez les patients atteints de vascularites ou de collagénoses. En raison de la toxicité liée au traitement par le cyclophosphamide chez ces sujets à risque, notamment en termes d'infections, nous avons étudié s'il existait une relation entre les paramètres pharmacocinétiques et la survenue des effets indésirables. Les résultats ont montré que les paramètres pharmacocinétiques du cyclophosphamide et de son métabolite sont comparables à ceux retrouvés chez le patient cancéreux. Cependant la variabilité inter-individuelle est plus importante dans notre étude [. . . ]Cyclophosphamide is an alkylating agent widely used for the treatment of malignant dis eases. It also has been used to treat systemic vasculitides. This immunosuppressive therapy, given in association with corticosteroids, has markedly improved the prognosis of these diseases. Although the pharmacokinetics of cyclophosphamide in cancer patients have been well documented, no information has been reported on cyclophosphamide pharmacokinetics in patients with systemic vasculitis and connectivitis. The aim of this study was to evaluate the concentrations and pharmacokinetic parameters of cyclophosphamide and its key circulating intermediate metabolite, 4-hydroxycyclophosphamide/aldophosphamide, in these patients and to define a relationships between pharmacokinetic parameters and toxic effects. The results are consistent with those obtained for cancer patients, in spite of a wide inter-patient variability of cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide concentrations in our study [. . . )
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Lo, Kwun-hang Kenny. "Effects of cyclophosphamide on ulcer in rat stomachs /". View the Table of Contents & Abstract, 2004. http://sunzi.lib.hku.hk/hkuto/record/B30708825.
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盧冠恆 i Kwun-hang Kenny Lo. "Effects of cyclophosphamide on ulcer in rat stomachs". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B45010158.
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Maynard-Faure, Patricia. "Synthèse d'analogues bicycliques préactives du cyclophosphamide et de l'aldophosphamide". Lyon 1, 1997. http://www.theses.fr/1997LYO10268.
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Ce memoire de these concerne l'etude de voies de synthese de nouveaux analogues du cyclophosphamide et de l'aldophosphamide. Apres avoir rappele la place du cyclophosphamide, agent cancerostatique le plus utilise en clinique humaine, dans l'arsenal des medicaments anticancereux, nous avons passe en revue les nombreux analogues deja synthetises en vue d'obtenir des composes a index therapeutique plus eleve. Nous presentons ensuite des voies de syntheses possibles pour des derives bicycliques preactives cibles ne necessitant pas d'activation biologique. Ce travail a permis de completer l'etude des voies d'acces au 3-n,n-bis (2-chloroethyl) amino -3-oxo-2-aza-4,9-dioxa-3-phosphabicyclo- (4, 3, 0) nonane precedemment synthetise, mais aussi de preparer de nouveaux analogues spiranniques en serie furanique et pyranique. Il a ete largement etendu en serie sucre par la preparation de composes du meme type derives du d-arabinose et du d-glucose. Ces preparations ont ete l'occasion de mettre au point de nouvelles methodologies, concernant notamment la synthese apres allongement de chaine d'azidoalcools originaux derives de l'arabinose et la n-glycosylation intramoleculaire de phosphoramides. La determination de la structure des nouveaux composes a necessite une analyse approfondie au moyen des techniques de resonance magnetique nucleaire les plus recentes, apportant par la-meme de nouvelles informations sur les facteurs influencant la geometrie des heterocycles du type oxazaphosphorinane. L'existence de conformations non chaises semble etre ainsi la regle pour des structures steriquement contraintes.
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Lu, Hong. "Pharmacokinetic and drug metabolism studies of cyclophosphamide and ifosfamide /". The Ohio State University, 1998. http://rave.ohiolink.edu/etdc/view?acc_num=osu148795015360318.
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Li, Zhaoyang. "DNA alkylation by active metabolites of Cyclophosphamide and Ifosfamide /". The Ohio State University, 1999. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488192960169091.
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Klinger, Mary Beth. "Neuroplasticity of Micturition Reflex Pathways with Cyclophosphamide-Induced Cystitis". ScholarWorks @ UVM, 2008. http://library.uvm.edu/dspace/bitstream/123456789/173/1/marybethklingerfinal.pdf.
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Ren, Song. "Metabolism of cyclophosphamide : implications for hematopoietic stem cell transplantation /". Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/7968.
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Sarkar, Anish Ali. "Inflammation Of The Taste Sensory System: Cyclophosphamide And Amifostine". ScholarWorks @ UVM, 2019. https://scholarworks.uvm.edu/graddis/1168.
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Chemotherapeutics are used extensively to treat cancer patients and often induce adverse effects, including taste dysfunctions. Disturbances in taste are detrimental to the overall well-being of cancer patients, causing malnutrition and weight loss that aggravate their condition even further. Inflammation due to an infection of the taste sensory system as previously shown, has detrimental effects on the taste sensation. Our study focused on if chemotherapy induced an inflammatory response in the taste buds using cyclophosphamide (CYP), a pro-drug. Once metabolized by the P450 enzyme complex, its primary metabolite functions as an alkylating agent, involved in inhibiting cell replication cycle and cell death. We used immunohistochemistry and fluorescent microscopy to analyze and observe the expression of the pro-inflammatory cytokine TNF-α in different types of taste sensory cells. Previously we found that a sulfhydryl cytoprotective drug, amifostine, can prevent taste bud damage and therefore we asked if it could prevent an inflammatory response. Our research observed an inflammatory response in both Type II and Type III cells in taste buds of fungiform and circumvallate papilla. Type II cells showed a peak response at 8- and 24-hour post-CYP injection whereas Type III cells had a peak expression at 24-hour post-CYP injection in the circumvallate papillae. Pre-treatment with amifostine appeared to prevent an inflammatory response within taste buds from CYP induced cytokine response. Identifying inflammation as a potential factor in taste related disorders could help clinicians develop better treatment modalities such as cytoprotective drugs preventing chemotherapy induced long term adverse effects such as malnutrition. In the future, we would like to expand our research to investigate expression of other pro-inflammatory cytokines and possible signaling mechanisms that could be responsible for CYP-induced inflammatory response in Type III cells.
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Henin, Coralie. "Potentialisation de la réponse immunitaire anti-tumorale par le cyclophosphamide". Doctoral thesis, Universite Libre de Bruxelles, 2017. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/252210.
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À ce jour, il est connu que le succès des traitements chimiothérapeutiques, outre l’effet cytotoxique direct sur les cellules tumorales, repose sur la contribution du système immunitaire. Nos travaux de recherche montrent que le traitement au cyclophosphamide de souris DBA/2 porteuses du mastocytome P815 induit le rejet de la tumeur, ainsi qu’une protection à long terme, de façon dépendante de la présence des lymphocytes T CD4+ et CD8+. De plus, le rejet du mastocytome P815 corrèle avec une augmentation de l’infiltration au sein de la tumeur de lymphocytes T CD8+ spécifiques d’un antigène muté. Lors de ce travail, nous avons tenté d’identifier les mécanismes moléculaires et cellulaires impliqués dans le rejet du mastocytome P815 induit suite à un traitement au cyclophosphamide. Dans ce but, les lymphocytes T CD8+ spécifiques de l’antigène muté, infiltrant un mastocytome P815 en progression ou en régression (suite à un traitement au cyclophosphamide), ont été analysés afin de mettre en évidence des caractéristiques phénotypiques et/ou fonctionnelles associées à ces populations de cellules T CD8+. Le traitement au cyclophosphamide conduit à l’infiltration de lymphocytes T CD8+ effecteurs en phase terminale de différenciation (KLRG1+ CD27- Eomes+ Perforin+) au sein de la tumeur, alors que les lymphocytes T CD8+ présents dans le microenvironnement tumoral du mastocytome P815 en progression possèdent un phénotype de cellules dysfonctionnelles (PD-1+ LAG-3+ Ki67-). Les IFN-I sont impliqués, au moins partiellement, dans l’acquisition du phénotype effecteur des cellules puisque leur inhibition entraine une augmentation de l’expression du récepteur PD-1.Ces résultats amènent à une meilleure compréhension des mécanismes par lesquels le cyclophosphamide régule l’amplitude et la qualité des réponses immunes spécifiques de la tumeur. Outre un effet quantitatif qui se traduit par l’expansion et l’infiltration dans la tumeur de lymphocytes T CD8+ spécifiques de l’antigène muté, cet agent chimiothérapeutique contribue au rejet du mastocytome P815 en favorisant le développement de lymphocytes T CD8+ effecteurs. La compréhension des effets immunomodulateurs d’un traitement chimiothérapeutique présente un intérêt majeur pour l’amélioration des thérapies en oncologie, tant en ce qui concerne l’immunothérapie que les combinaisons de traitement.An important question is how chemotherapy may (re-)activate tumor-specific immunity. In this study, we provide a phenotypic, functional and genomic analysis of tumor-specific CD8+ T cells in tumor (P815)-bearing mice, treated or not with cyclophosphamide. Our data show that chemotherapy favors the development of effector-type lymphocytes in tumor bed, characterized by higher KLRG-1 expression, lower PD-1 expression and increased cytotoxicity. This suggests re-engagement of T lymphocytes into the effector program since most T cells are dysfunctional in the tumor microenvironment before cyclophosphamide treatment. IFN-I appears involved in this remodelling. Our findings provide some insight into how cyclophosphamide regulates the amplitude and quality of tumor-specific immune responses.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
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Delgado, Zambrano Luis Fernando. "Bioréacteur à membrane externe pour le traitement d'effluents contenant des médicaments anticancéreux : élimination et influence du cyclophosphamide et de ses principaux métabolites sur le procédé". Thesis, Toulouse, INPT, 2009. http://www.theses.fr/2009INPT005G/document.
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La problématique concernant la présence et les risques potentiels liés aux micropolluants dans l'environnement est devenue une préoccupation d'actualité. Aujourd'hui, les stations d'épuration ne sont pas en mesure de traiter de manière adéquate ce nouveau type de pollution. Dans le cadre de cette thèse, l'application de la technologie des bioréacteurs à membrane a été envisagée afin d'évaluer leur potentiel pour la dégradation d'un médicament anticancéreux : le cyclophosphamide (CP). Les objectifs de cette étude sont d'une part évaluer le potentiel des bioréacteurs à membrane pour la dégradation du cyclophosphamide, ainsi que pour l'élimination de sa toxicité, d'autre part rechercher l'effet du CP et de ses métabolites sur les performances globales du procédé et sur l'activité de la biomasse épuratrice ainsi que sur les propriétés physico-chimiques de la liqueur mixte et les conséquences sur le colmatage. Deux âges de boues ont été évalués, 50 jours lors de la première campagne et 70 jours lors de la deuxième. L'élimination du CP et du métabolite 4-Keto-CP durant les deux campagnes expérimentales est d'environ 80% pour les deux composés. Les processus d'adsorption et de biodégradation contribuent à l'élimination du CP de l'eau résiduaire traitée. Le cocktail de CP et ces métabolites aux conditions opératoires étudiées n'a pas d'influence significative sur l'élimination globale de la DCO et de l'azote total. Cependant, la toxicité du cocktail des composés pharmaceutiques sur la boue activée modifie les caractéristiques de la matrice biologique : Une diminution de la production de boues du BÀM R1 CP par rapport au BÀM R2 contrôle est observée. La présence du CP et ses principaux métabolites stimule les mécanismes de survie et de production des EPS avec une production légèrement plus forte des polysaccharides que des protéines. Les résultats mettent en évidence que la réponse des boues activées des BÀM au cisaillement est dépendante de la présence de ces molécules. Cette étude démontre au final l'intérêt des BÀM pour traiter ce type d'effluents, et limiter la pollution relarguée dans le milieu naturelIn hospital or pharmaceutical discharges, but also in wastewater treatment plants and more generally in the aquatic environment, toxics pollutants have been identified. Some pharmaceuticals are not completely eliminated in the municipal wastewater treatment plants and are discharged as contaminants into receiving waters. The application of membrane bioreactor process is investigated here with the aim of evaluating the potential for removal of cyclophosphamide (CP). In this study, two membrane bioreactors (MBR) were operated: one of the MBR served as a control, whereas to the other CP and its main metabolites were continuously added. Two sludge retention times were assessed, 50 days and 70 days. Removal of CP in a MBR and its effects on the membrane performance, COD and total nitrogen (TN) removal efficiency were studied. CP and 4-Ketocyclophosphamide removals up to 80% were achieved under studied operating conditions. The sludge adsorption and biodegradation (cometabolism) play an important role in the process of CP removal. CP and its metabolites toxicity do not alter COD and total nitrogen removal efficiency of MBRs. However, it induces a modification of the biological suspended solids and in doing so a modification on the membrane fouling: a decrease in the production of sludge MBR CP compared to MBR control is observed; the presence of CP and its main metabolites stimulates mechanisms of protection and production of EPS with a slightly higher production of polysaccharides than proteins. The results underline that the response of activated sludge to shear stress is dependent on the presence of these molecules. This study demonstrates the interest of MBR to treat this type of effluent and reduce the pollution released into the environment
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Cárcano, Flavio Mavignier [UNESP]. "Quimioterapia à base de ciclofosfamida metronômica no tratamento de pacientes com câncer de próstata resistente à castração". Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/88070.
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O câncer de próstata é o sexto tipo de câncer mais comum no mundo e cerca de três quartos dos casos ocorrem a partir dos 65 anos. O tratamento paliativo inicial para doença avançada contempla a castração, mas invariavelmente, metástases e resistência é desenvolvida em algum momento, quando então a quimioterapia é oferecida. Entretanto, a busca por tratamentos menos tóxicos se faz necessária para atender uma população cada vez mais idosa e com comorbidades que limitam o uso de drogas convencionais. As combinações à base de Ciclofosfamida oral metronômica têm sido uma opção atraente e merecem melhor avaliação. Objetiva-se avaliar aqui, os fatores prognósticos e o melhor perfil de pacientes para receber este tipo de tratamento. Para isso, dados de pacientes com câncer de próstata metastáticos e resistentes à castração foram recuperados, nos quais tinham utilizado quimioterapia metronômica à base de Ciclofosfamida entre os anos de 2004 e 2009 no Hospital de Câncer de Barretos. Os dados de sobrevivência foram analisados pelo método de Kaplan Meier e o modelo de regressão proporcional de riscos de Cox foi aplicado para avaliar os fatores prognósticos. Cento e quatro pacientes foram avaliados e dois terços deles receberam quimioterapia metronômica à base de Ciclofosfamida como uma primeira linha de tratamento. A taxa de resposta do PSA foi de 32% e a mediana da sobrevivência livre de progressão foi de 6,3 meses (IC 95%, 5,1 - 7,4). A sobrevivência global mediana foi 14,4 meses (IC 95%, 11,1 -17,7). Performance Status (HR 2,4 e IC 95% 1,32 - 4,34; p= 0,004) e PSA pré-tratamento (HR 2,5 e IC 95% 1,33 - 4,81; p= 0,005) foram os fatores prognósticos mais significativos. Três grupos foram identificados com sobrevivências medianas de 8,0 meses (IC 95%, 5,0 - 11,1), 13,3 meses (IC 95%, 10,0 - 16,6) e 23,4 meses (IC 95%, 22,7 - 24,1), respectivamente...
Prostate cancer is the sixth more common worldwide and about two-thirds occurs in men of sixty-five or older. Palliative treatment of advanced disease has been initially done by castration, but invariably the disease become resistant anytime and standard-based chemotherapies are delivered. However, low-toxicity chemotherapies are aimed to treat a scenario of elderly frail. Metronomic cyclophosphamide-based chemotherapies has been attractive option and deserves better assessment. It aimed to assess prognostic factors and better profile to get this therapy. It was requested data of one hundred four metastatic castrate-resistant prostate cancer patients that had received metronomic cyclophosphamide-based chemotherapies between 2004 to 2009 at Barretos Cancer Hospital. Kaplan Meier method was applied to analyze survivals and Cox hazard regression model analysis was done to assess prognostic factors. Two-thirds of the study subjects have done first line metronomic cyclophosphamide-based chemotherapy. PSA response rate was 32% and median progression free-survival was 6,3 months (95% CI, 5,1 - 7,4). Median overall survival was 14,4 months (95% CI, 11,1 -17,7). Performance Status (HR 2,4 and 95% CI 1,32 - 4,34; p= 0,004) and baseline pretreatment PSA (HR 2,5 and 95% CI 1,33 - 4,81; p= 0,005) were the better prognostic factors. Three risk groups were identified achieving median survivals of 8,0 months (95% CI, 5,0 - 11,1), 13,3 months (95% CI, 10,0 - 16,6) and 23,4 months (95% CI, 22,7 - 24,1), respectively (log rank, p< 0,001). Intermediate group got also benefit with more actives drugs in selected cases of rescue proposes. In conclusion, metastatic castrate-resistant prostate cancer patients unfit to receive standard-based chemotherapies can get benefit with metronomic cyclophosphamide-based therapy. Performance Status and baseline pretreatment PSA have prognostic value in this setting. Is first ... (Complete abstract click electronic access below)
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Brain, Étienne. "Les alkylants oxazaphosphorines (cyclophosphamide et ifosfamide), la modulation de leur métabolisme hépatique et de leur pharmacocinétique". Paris 5, 2005. http://www.theses.fr/2005PA05S018.
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Le métabolisme hépatique des oxazaphosphorines cyclophosphamide et ifosfamide via les cytochromes P450 oscille entre une voie d'activation (4-hydroxylation) et une voie de toxification (N-déchloroéthylation). A l'aide d'inducteurs/inhibiteurs spécifiques des cytochromes P450 identifiés in vitro, il est possible de moduler in vivo ce métabolisme en terme pharmacocinétique. En clinique, la modalité de perfusion intraveineuse (continue vs courte) n'influence ni la pharmacocinétique ni la pharmacodynamique de l'ifosfamide dont le ratio d'activation est le plus défavorable, que ce soit en analyse non compartimentale ou en modélisation. A partir de 12 sujets traités selon les deux modalités (étude randomisée avec cross-over intra-patient), la coadministration de carbamazépine est la seule covariable d'influence retenue. Le modèle généraliste pharmacocinétique-pharmacodynamique final permet de simuler de nouveaux schémas posologiques à la recherche de meilleurs indices pharmacodynamiquesThe metabolism of both oxazaphosphorines cyclophosphamide and ifosfamide proceeds via liver cytochromes P450. It is best described as a balance between a true activation pathway (4-hydroxylation) and a presumed toxification pathway (N-dechloroethylation). The use of specific inducers/inhibitors of cytochromes P450 identified in vitro results in potentially useful pharmacokinetics modulation profiles in vivo. In clinical practice, there is no difference in ifosfamide pharmacokinetics and pharmacodynamics according to the schedule of intravenous infusion (continuous vs short), as found in both a non-compartmental analysis and a model development. In the pharmacokinetic model built from the data of 12 patients treated according to both schedules (randomized trial with intra-patient crossover), only comedication with carbamazépine was a significant covariable. The final generalist pharmacokinetic-pharmacodynamic model allows simulating new schedules looking for better therapeutic ratios
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Arms, Lauren. "Inflammation-Induced Plasticity of Micturition Reflex Pathways". ScholarWorks @ UVM, 2011. http://scholarworks.uvm.edu/graddis/9.
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Although a seemingly basic and simple behavior, micturition necessitates precise integration and coordination of multiple divisions of the nervous system: visceral sensory, somatic motor, sympathetic, parasympathetic, as well as voluntary control from higher brain/ brainstem centers. When coordination of this circuitry falters, the consequences can be devastating and include severely decreased quality of life and substantial economic burden. This dissertation project investigates the potential role(s) of inflammatory mediators in bladder sensory physiology with the long term goal of elucidating potential targets for intervention. The overall hypothesis is that inflammatory-induced changes in the urinary bladder or afferent projections ultimately lead to dysfunctional micturition symptoms. Using a rodent model of cyclophosphamide (CYP)-induced bladder inflammation, we examined the expression and function of the chemokine/ receptor pair, CXCL12/CXCR4, and the activated (phosphorylated) form of ubiquitous signaling molecule, AKT using a multidisciplinary approach that includes: immunohistochemistry, protein and transcript quantification techniques, and in vivo bladder physiology studies combined with pharmacological tools. Peripheral chemokine levels are elevated in patients with various chronic pelvic inflammatory/ pain syndromes including interstitial cystitis/bladder pain syndrome (IC/BPS) and are implicated in numerous inflammatory and mechanical pain models in rodents. However studies had not previously shown a direct functional role for chemokine signaling in micturition. We hypothesized that CXCL12 and CXCR4 would increase in the urinary bladder with CYP-induced bladder inflammation and that CXCR4 receptor blockade with AMD3100 would reduce CYP-induced bladder hyperreflexia. ELISA, immunohistochemical and qRT-PCR experiments demonstrate duration-dependent increases in CXCL12 and CXCR4 protein and transcript expression in specific tissue compartments of the urinary bladder, mainly the urothelium. In vivo studies provide evidence of a role for chemokine signaling in the mediation of micturition function. Intravesical infusion with AMD3100, a CXCR4 receptor antagonist, significantly reduced CYP-induced bladder hyperreflexia as evidenced by increased bladder capacity, intercontraction interval and decreased voiding frequency. AKT is a putative cellular survival signal, however, recent studies also implicate the signaling molecule in the induction and maintenance of pain processes, development of long term plasticity (e.g. LTP and central sensitization) and visceral inflammation. Functional studies addressing the contribution of pAKT in micturition have not been performed. We hypothesized that increasing pAKT levels would contribute to CYP-induced bladder hyperreflexia. Western blot and immunohistochemical studies demonstrated that phosphorylation of AKT increases in the whole urinary bladder with CYP-induced bladder inflammation in a tissue compartment- and time-dependent manner. Intravesical infusion with inhibitors of AKT phosphorylation, AKT Inhibitor IV and deguelin, significantly improved symptoms of CYP-induced bladder hyperreflexia suggesting a functional role for pAKT in bladder physiology. These studies demonstrate the functional capacity of inflammatory mediators and inflammatory associated signaling pathways in micturition reflex pathways. Chemokine signaling via the CXCR4 receptor and upstream activators of AKT may provide therapeutic targets with respect to inflammatory-induced bladder sensory physiology dysfunction.
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Manley, Jennifer J. "An assessment of DNA damage in rat sperm following cyclophosphamide treatment". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0026/MQ50826.pdf.
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Xie, Hanjing. "Pharmacogenetic and pharmacokinetic studies of cyclophosphamide : in cell, animal and human /". Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-785-1/.
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Kelly, Sara M. "Paternal cyclophosphamide exposure exerts deleterious effects on early rat embryo development". Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41634.
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Cyclophosphamide is an alkylating agent which has deleterious effects on reproduction in both males and females. When administered to male rats in chronic low doses (6 mg/kg/day), cyclophosphamide caused a dose-dependent increase in post-implantation death of the offspring. On day 7 of gestation, two days after implantation, the inner cell mass-derived embryonic tissues were retarded or absent while trophectoderm-derived extraembryonic tissues appeared normal. The preimplantation growth of embryos sired by cyclophosphamide-treated males was affected; as early as day 3 there was a significant decrease in cell number and in DNA synthesis. On day 3, there was no ultrastructural evidence of active cell death, and embryos underwent compaction, despite their decreased cell numbers. On day 4, embryos sired by treated males had less than half the cell number of controls: this decrease was not lineage-specific. A minority of embryos sired by treated males did not cavitate and showed signs of autophagic death on day 4 of gestation. The majority of embryos sired by treated males were able to cavitate and differentiate morphologically to form small blastocysts. Thus the target of cyclophosphamide damage may be a paternal gene more important for cell proliferation than for cell differentiation in the preimplantation rat embryo.
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Li, Li. "Modification of antitumor immunity by cyclophosphamide given after active specific immunizaition". Kyoto University, 1998. http://hdl.handle.net/2433/182266.
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Roux, Stéphan. "Ciblage des Toll-Like récepteurs en immunithérapie antitumorale : Applications et perspectives thérapeutiques". Paris 11, 2009. http://www.theses.fr/2009PA11T013.
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Maillefert, Thierry. "Traitement des formes graves de connectivites et de vascularites par le cyclophosphamide en perfusions séquentielles : à propos de 20 cas". Montpellier 1, 1990. http://www.theses.fr/1990MON11069.
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Codrington, Alexis. "The impact of the chemotherapeutic drug cyclophosphamide on rat spermiogenic chromatin remodeling /". Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103039.
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Male reproductive health is of growing concern, as male toxicant exposure can affect progeny outcome; sperm chromatin structure integrity may be a contributing factor. The formation of mature sperm involves the expression of numerous proteins involved in organizing and packaging the chromatin in a specific manner; this ensures transmission and participation of the paternal genome in embryogenesis. Exposure of male rats to cyclophosphamide as spermatid chromatin is remodeled has an adverse effect on embryo development. The hypothesis of this thesis is that cyclophosphamide exposure causes genetic damage and alters the sperm proteome, thus disrupting components of chromatin condensation and organization during spermiogenesis. The first objective was to assess the phase specificity of the susceptibility of spermiogenic germ cells to cyclophosphamide-induced DNA damage. Spermatozoa were analyzed for DNA strand breaks using the comet assay. Cyclophosphamide-induced DNA damage was dose-related and accumulated over time. Germ cell phase-specific damage was maximal during midspermiogenesis; this reflects an increased susceptibility of step 9-14 spermatids at a key point in sperm chromatin remodeling, the histone-protamine exchange. The second objective was to examine the sperm chromatin structure and basic proteome. Multiple assays demonstrated that the effects of cyclophosphamide on sperm chromatin structure were also germ cell-phase specific; midspermiogenic spermatids were most sensitive. Sperm were less condensed with reduced total thiol and protamine contents. The sperm basic proteome was also altered; identified proteins are involved in a variety of spermiogenic and fertilization events. The nuclear matrix organizes chromatin into loop domains, and various components of somatic cell matrices are targets for chemotherapeutic agents. Therefore the last objective of this study was to assess the effect of cyclophosphamide exposure on the protein profile of the sperm nuclear matrix. The expression of several nuclear matrix protein components, a number of which were identified for the first time, was altered following drug exposure. Together these results show that cyclophosphamide alters male germ cell chromatin remodeling at both the DNA and protein level; this could alter sperm function and thus explain the adverse effects on early embryo development.
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Gerfen, Ashlee. "Chemomobilization with cyclophosphamide and filgrastim in multiple myeloma patients following lenalidomide treatment". The University of Arizona, 2012. http://hdl.handle.net/10150/623611.
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Class of 2012 AbstractSpecific Aims: Autologous stem cell transplant (ASCT) is the current gold standard following induction therapy to improve survival of multiple myeloma (MM). Lenalidomide (LEN) is used for treatment of MM before ASCT, but exposure may impair autologous peripheral blood stem cell (PBSC) mobilization. Chemomobilization with cyclophosphamide (CTX) has not been evaluated in this setting. CTX + filgrastim was investigated to determine if LEN-associated mobilization impairment can be abrogated. Methods: 36 pts (group A=12 pts who received ≥2 cycles of LEN and group B=24 pts without LEN) were analyzed retrospectively. Baseline characteristics were matched (p>0.05 for all variables). All pts received CTX (median group B, 1.5g/m2; median group A, 3gm/m2(p=0.18)) and filgrastim 10μg/kg/day. Primary outcomes include number of CD34+ cells collected and number of leukapheresis sessions. Secondary outcomes include failure to collect CD34+ cells and total CD34+ cells collected after second leukapheresis. Main Results: Total median number of CD34+ cells collected in group B=9.15x106/kg CD34+ cells and group A=7.43x106/kg CD34+ cells (p=0.159). Median number of apheresis sessions in group B=2 and group A=3 (p=0.42). Two of 12 pts with antecedent LEN usage failed to collect while no patient without previous LEN exposure failed to collect (p=0.105). Total number of CD34+ cells collected after 2 apheresis sessions for group B=8.13x106/kg CD34+ cells and group A=3.34x106/kg CD34+ cells (p=0.06). Conclusions: Chemomobilization with CTX + filgrastim yields robust PBSC collections irrespective of antecedent lenalidomide. There was a trend towards lesser PBSC collection in LEN-treated pts.
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Gerfen, Ashlee, i Myke Green. "Chemomobilization with Cyclophosphamide and Filgrastim in Multiple Myeloma Patients Following Lenalidomide Treatment". The University of Arizona, 2012. http://hdl.handle.net/10150/614472.
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Class of 2012 AbstractSpecific Aims: Autologous stem cell transplant (ASCT) is the current gold standard following induction therapy to improve survival of multiple myeloma (MM). Lenalidomide (LEN) is used for treatment of MM before ASCT, but exposure may impair autologous peripheral blood stem cell (PBSC) mobilization. Chemomobilization with cyclophosphamide (CTX) has not been evaluated in this setting. CTX + filgrastim was investigated to determine if LEN-associated mobilization impairment can be abrogated. Methods: 36 pts (group A=12 pts who received ≥2 cycles of LEN and group B=24 pts without LEN) were analyzed retrospectively. Baseline characteristics were matched (p>0.05 for all variables). All pts received CTX (median group B, 1.5g/m2; median group A, 3gm/m2(p=0.18)) and filgrastim 10µg/kg/day. Primary outcomes include number of CD34+ cells collected and number of leukapheresis sessions. Secondary outcomes include failure to collect CD34+ cells and total CD34+ cells collected after second leukapheresis. Main Results: Total median number of CD34+ cells collected in group B=9.15x106/kg CD34+ cells and group A=7.43x106/kg CD34+ cells (p=0.159). Median number of apheresis sessions in group B=2 and group A=3 (p=0.42). Two of 12 pts with antecedent LEN usage failed to collect while no patient without previous LEN exposure failed to collect (p=0.105). Total number of CD34+ cells collected after 2 apheresis sessions for group B=8.13x106/kg CD34+ cells and group A=3.34x106/kg CD34+ cells (p=0.06). Conclusions: Chemomobilization with CTX + filgrastim yields robust PBSC collections irrespective of antecedent lenalidomide. There was a trend towards lesser PBSC collection in LEN-treated pts.
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Qiu, Ruolun. "ABCC2 (cMOAT) : role in 4-hydroxycyclophosphamide elimination from the liver and survival of high dose cyclophosphamide regimens /". Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/7962.
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Cárcano, Flavio Mavignier. "Quimioterapia à base de ciclofosfamida metronômica no tratamento de pacientes com câncer de próstata resistente à castração /". Botucatu : [s.n.], 2011. http://hdl.handle.net/11449/88070.
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Orientador: Sérgio Vicente SerranoBanca: Odair Carlito Michelin
Resumo: O câncer de próstata é o sexto tipo de câncer mais comum no mundo e cerca de três quartos dos casos ocorrem a partir dos 65 anos. O tratamento paliativo inicial para doença avançada contempla a castração, mas invariavelmente, metástases e resistência é desenvolvida em algum momento, quando então a quimioterapia é oferecida. Entretanto, a busca por tratamentos menos tóxicos se faz necessária para atender uma população cada vez mais idosa e com comorbidades que limitam o uso de drogas convencionais. As combinações à base de Ciclofosfamida oral metronômica têm sido uma opção atraente e merecem melhor avaliação. Objetiva-se avaliar aqui, os fatores prognósticos e o melhor perfil de pacientes para receber este tipo de tratamento. Para isso, dados de pacientes com câncer de próstata metastáticos e resistentes à castração foram recuperados, nos quais tinham utilizado quimioterapia metronômica à base de Ciclofosfamida entre os anos de 2004 e 2009 no Hospital de Câncer de Barretos. Os dados de sobrevivência foram analisados pelo método de Kaplan Meier e o modelo de regressão proporcional de riscos de Cox foi aplicado para avaliar os fatores prognósticos. Cento e quatro pacientes foram avaliados e dois terços deles receberam quimioterapia metronômica à base de Ciclofosfamida como uma primeira linha de tratamento. A taxa de resposta do PSA foi de 32% e a mediana da sobrevivência livre de progressão foi de 6,3 meses (IC 95%, 5,1 - 7,4). A sobrevivência global mediana foi 14,4 meses (IC 95%, 11,1 -17,7). Performance Status (HR 2,4 e IC 95% 1,32 - 4,34; p= 0,004) e PSA pré-tratamento (HR 2,5 e IC 95% 1,33 - 4,81; p= 0,005) foram os fatores prognósticos mais significativos. Três grupos foram identificados com sobrevivências medianas de 8,0 meses (IC 95%, 5,0 - 11,1), 13,3 meses (IC 95%, 10,0 - 16,6) e 23,4 meses (IC 95%, 22,7 - 24,1), respectivamente ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Prostate cancer is the sixth more common worldwide and about two-thirds occurs in men of sixty-five or older. Palliative treatment of advanced disease has been initially done by castration, but invariably the disease become resistant anytime and standard-based chemotherapies are delivered. However, low-toxicity chemotherapies are aimed to treat a scenario of elderly frail. Metronomic cyclophosphamide-based chemotherapies has been attractive option and deserves better assessment. It aimed to assess prognostic factors and better profile to get this therapy. It was requested data of one hundred four metastatic castrate-resistant prostate cancer patients that had received metronomic cyclophosphamide-based chemotherapies between 2004 to 2009 at Barretos Cancer Hospital. Kaplan Meier method was applied to analyze survivals and Cox hazard regression model analysis was done to assess prognostic factors. Two-thirds of the study subjects have done first line metronomic cyclophosphamide-based chemotherapy. PSA response rate was 32% and median progression free-survival was 6,3 months (95% CI, 5,1 - 7,4). Median overall survival was 14,4 months (95% CI, 11,1 -17,7). Performance Status (HR 2,4 and 95% CI 1,32 - 4,34; p= 0,004) and baseline pretreatment PSA (HR 2,5 and 95% CI 1,33 - 4,81; p= 0,005) were the better prognostic factors. Three risk groups were identified achieving median survivals of 8,0 months (95% CI, 5,0 - 11,1), 13,3 months (95% CI, 10,0 - 16,6) and 23,4 months (95% CI, 22,7 - 24,1), respectively (log rank, p< 0,001). Intermediate group got also benefit with more actives drugs in selected cases of rescue proposes. In conclusion, metastatic castrate-resistant prostate cancer patients unfit to receive standard-based chemotherapies can get benefit with metronomic cyclophosphamide-based therapy. Performance Status and baseline pretreatment PSA have prognostic value in this setting. Is first ... (Complete abstract click electronic access below)
Mestre
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Jezequel, Laetitia. "Développement d'approches prédictives pour l'ingénierie des protéines par évolution dirigée et application au développement d'une thérapie anticancéreuse". Paris 11, 2009. http://www.theses.fr/2009PA112260.
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Le souhait de réduire des effets secondaires associés aux anticancéreux a mené à considérer l’utilisation de prodrogues activables au site d’action, comme la cyclophosphamide (CPA). La CPA est activée majoritairement par le CYP2B6 humain avec une faible efficacité, obligeant à l’utilisation de concentrations importantes de prodrogue. Celles-ci peuvent être réduites par transfection au niveau de la tumeur d’un gène codant pour un P450 optimisé, possédant une efficacité catalytique élevée vis-à-vis de la CPA tout en étant le moins immunogène possible. Pour ce faire, en partant de la modélisation du CYP2B6 et du CYP2B11, forme canine à bas Km pour l'activation de la CPA, un gène synthétique du CYP2B11 pour l'expression dans la levure a été dessiné et divisé en 15 "modules" structuraux. Quinze chimères à points de jonction définis entre les deux CYP2Bs ont ensuite été construites par échange de ces modules, via une méthode originale de génération de banques ordonnées de chimères, SIGNAL, indépendante de l'homologie de séquence des enzymes parentaux. SIGNAL, à mi-chemin entre les processus classiques d'évolution dirigée et de mutagenèse dirigée, nous a permis, après analyse fonctionnelle des chimères, de mieux comprendre le mécanisme de métabolisation de la CPA par les deux enzymes et d'identifier des modules structuraux jouant potentiellement un rôle important dans la haute affinité du CYP2B11. En parallèle, la mise au point d'un système de sélection à haut débit des variants les plus efficaces pour l'activation de la CPA dans la levure, basé sur le principe du gène rapporteur, a été débutée, afin de pouvoir raffiner l'optimisation du P450 par un processus de mutagenèse aléatoireOne of the possibilities considered to reduce the side effects associated to chemotherapeutic treatments was to use cytotoxic prodrugs, like cyclophosphamide (CPA), activated directly into the tumors. CPA is mainly activated with a low efficiency by human CYP2B6, so large doses of prodrug are used to induce a response. The transfection of an optimized CYP gene, possessing a high catalytic efficiency towards CPA while presenting a low immunogenicity, is a route to lower active doses. For this purpose, the canine CYP2B11, which exhibits a low Km for CPA activation, was modelled and divided into 15 structural "modules". A synthetic CYP2B11 gene was designed to permit a good expression in yeast and to swap defined modules between the human and canine forms. An original sequence – independent method, SIGNAL, was developed, which allowed the construction of 15 chimeras with defined junction points. This ordered library, halfway between random directed evolution and defined directed mutagenesis, permitted the generation of targeted diversity, which do not need a high-throughput approach for functional analysis. Resulting information highlighted critical segments for CPA metabolism, which are potentially involved in the high CYP2B11 affinity. The P450 functional optimization could be further enhanced by a random mutagenesis process, which requires, in contrast, a high throughput screening system. Its development in S. Cerevisiae was initiated using a reporter gene method
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Daillere, Romain. "Impact du microbiote intestinal sur l’efficacité anti-tumorale de la chimiothérapie par cyclophosphamide". Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS073.
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Plus de 50 ans après son approbation par les agences réglementaires, le cyclophosphamide (CTX) reste une drogue aux propriétés variées et aux effets pléiotropiques couramment utilisée en clinique. Cet agent cytotoxique, administré en cancérologie, possède des propriétés immuno-modulatrices et stimule les réponses immunitaires anti-tumorales. A doses métronomiques, le CTX induit notamment une polarisation des splénocytes CD4+ vers un profil Th1 et Th17, caractérisés par la sécrétion d’IFNet d’IL-17, nécessaire à l’activité tumoricide du CTX. Comme tout agent cytotoxique, le CTX cible les cellules en prolifération, qu’elles soient normales ou cancéreuses. Le CTX compromet ainsi l’intégrité de la barrière intestinale et l’homéostasie du tractus digestif. Nous avons démontré que l’individu sous CTX a une fragilisation de la barrière intestinale qui permet la rupture de la tolérance de celui-ci à sa flore commensale et son immunisation contre certaines espèces bactériennes. L’immunisation anti-bactérienne est composée de lymphocytes effecteurs CD4+, appelés « Th17 pathogéniques » et producteurs d’IL-17 et d’IFN, qui aident les lymphocytes anti-tumoraux à endiguer la croissance de tumeurs chez la souris. Nous avons mis en évidence que la stérilisation des animaux avec des antibiotiques à large spectre ou ciblant certaines populations bactériennes comme la vancomycine (ciblant les Gram+) et la colistine (ciblant les Gram-), abrogent l’efficacité anti-tumorale du CTX. Par ailleurs, nous avons identifié deux bactéries, une bactérie Gram+ Enterococcus hirae, capable de restaurer l’efficacité de cette chimiothérapie en induisant la polarisation de réponses Th1 et pTh17 stimulant la mise en place de réponses lymphocytaires T CD4 et T CD8 dirigées contre des antigènes tumoraux et une bactérie Gram- Barnesiella intestinihominis, impliquée dans la mise en place de réponses mémoires induites par la combinaison CTX+vaccin. Ces travaux démontrent ainsi l’importance de la flore intestinale dans la réponse à la chimiothérapie par CTXMore than 50 years after its approval by the Food and Drug Administration, cyclophosphamide (CTX) remains a drug with miscellaneous properties currently used in anti-cancer chemotherapy. This cytotoxic agent has immuno-modulatory properties and stimulate anti-tumoral immune responses. At metronomic doses, CTX induces the polarisation of splenocytes toward a Th1 and Th17 profile, characterized by the secretion of IFN et IL-17, both mandatory for the tumoricidal activity of this drug. CTX, as cytotoxic agent, targets proliferating cells, either normal or tumoral. Indeed, CTX is responsible for disrupting the gut barrier integrity as well as intestinal homeostasis. We have shown that people treated with CTX have a weaker intestinal barrier which breaks the tolerance toward the intestinal microbiota and leads to its immunization against some bacterial strains. This immunization is composed of CD4+ effector lymphocytes called « pathogenic Th17 » producing IFN and IL-17, which helps tumor-infiltrating lymphocytes to control the tumor growth in mice. Broad spectrum antibiotics as well as vancomycin (which mainly kills Gram positive bacteria) and colistin (which mainly eliminates Gram negative bacteria) all compromised the full-blown anticancer activity of CTX in vivo. Moreover, we have identified two bacteria, Enterococcus hirae and Barnesiella intestinihominis, able to rescue the efficacy of CTX abolished with antibiotics. E. hirae, a Gram+ bacterium, elicits Th1 immune responses and pathogenic Th17 cells capable of enhancing tumor-specific CD4+ and CD8+ T cell responses against candidate tumor antigens associated with tumor control. B. intestinihominis, a Gram- bacterium, was able to rescue the long term cognate responses lost with broad spectrum antibiotics or colistin treatment. Our data underscore the role of the gut microbiota in the efficacy of chemotherapy by CTX
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Li, Siu-ming Ian. "A study of cyclophosphamide on dextran sulfate sodium-induced ulcerative colitis in mice". Click to view the E-thesis via HKUTO, 2004. http://sunzi.lib.hku.hk/hkuto/record/B31971994.
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Wathelet, Nathalie. "Etude de l'effet du cyclophosphamide sur la réponse immunitaire spécifique du mastocytome P815". Doctoral thesis, Universite Libre de Bruxelles, 2012. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209566.
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La découverte des antigènes tumoraux dans les années 1980s a permis d’envisager l’élaboration de protocoles de vaccination de patients cancéreux. Les résultats obtenus chez les patients traités sont prometteurs mais encore insuffisants et la chimiothérapie reste, à ce jour, régulièrement utilisée dans le traitement de tumeurs.\
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
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Li, Siu-ming Ian, i 李紹銘. "A study of cyclophosphamide on dextran sulfate sodium-induced ulcerative colitis in mice". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31971994.
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Anwer, Faiz, Seongseok Yun, Anju Nair, Yusuf Ahmad, Ravitharan Krishnadashan i H. Joachim Deeg. "Severe Refractory Immune Thrombocytopenia Successfully Treated with High-Dose Pulse Cyclophosphamide and Eltrombopag". Hindawi, 2015. http://hdl.handle.net/10150/617180.
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UA Open Access Publishing FundSevere refractory ITP is clinically challenging and a variety of single or combination chemotherapies have been tried with limited outcome. We report a case of ITP that was unresponsive to multiple agents including high-dose steroid, IVIG, Rho(D) immune globulin, rituximab, cyclosporine, azathioprine, vincristine, mycophenolate mofetil, romiplostim, and eltrombopag; however, it achieved complete remission with combination treatment of cyclophosphamide and eltrombopag.
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Gardner, R., i John Bossaer. "Possible Drug-Induced Pancreatitis in a Patient Receiving Cyclophosphamide, Vincristine, and Prednisone Chemotherapy". Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/7797.
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Drug-induced pancreatitis is a condition characterized by sudden inflammation of the pancreas that can be mild or severe but usually subsides. Signs and symptoms consist of abdominal pain, nausea/vomiting, low-grade fever and pain radiating to the lower back. The incidence of acute drug-induced pancreatitis is approximately 2% but in patients that have disease states that predispose them to the development of pancreatitis, such as malignancy, hypercalcemia, tumor lysis syndrome, and immunosuppression it is found to be much higher. Conditions that should be considered in the differential diagnosis are cholelithiasis, hyperlipidemia, pancreatic tumor and alcoholism. Additionally, several medications have been reported to have an association with inducing pancreatitis. The focused medications are cyclophosphamide, vincristine and prednisone. All three of these drugs come with a probable association of medications that can induce pancreatitis. Having risk factors and potential drugs that could induce pancreatitis make it challenging to pinpoint the cause.
A 79-year-old male presented to the hospital with generalized weakness and altered mental status lasting approximately 5 days. A clinical diagnosis of angioimmunoblastic T-cell lymphoma was made and chemotherapy was started during the stay. CVP (cyclophosphamide, vincristine, and prednisone) chemotherapy was given along with a rasburicase for potential tumor lysis syndrome. All labs were within normal limits prior to chemotherapy except for calcium, which was 10.9mg/dL and 12.42mg/dL after correction for the albumin being 2.1gm/dL. The following day the patient complained of severe abdominal pain and had mild abdominal distention. A diagnosis of pancreatitis was made after labs revealed: amylase >600 U/L, corrected calcium 12.04mg/dL, glucose 260mg/dL, a bump in BUN from 34 to 50mg/dL and a normal lipid panel. The patient also had a CT scan that revealed cholelithiasis. Subsequently the chemotherapy was stopped and normal saline was given at 50mL/hr due to his heart failure with reduced ejection fraction. Upon discontinuation of the chemotherapy, the patients abdominal pain resolved within 2 days and labs started to return to normal. Labs revealed: corrected calcium 10.5mg/dL, glucose 98mg/dL and BUN 40mg/dL. The chemotherapy agent was switched to intrathecal methotrexate, in which the patient had no trouble tolerating and the abdominal pain never returned. Ultimately, the patient developed worsening heart failure and 20 days later expired.
The complexity of pinpointing conditions, risk factors, or drug causes for pancreatitis is outlined in this case. This patient had several risk factors for developing pancreatitis such as malignancy and hypercalcemia but didn’t have any signs/symptoms. After CVP chemotherapy was started, the signs/symptoms matched the labs and clinical diagnosis but cholelithiasis revealed. Once the chemotherapy was stopped all signs/symptoms subsided and labs returned to normal. The most likely cause was the chemotherapy due to the timeline from initiation of therapy to the onset of pancreatitis symptoms but this case is extremely complex due to other conditions and risk factors.
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Horiuchi, Yuka. "Lactoferrin is associated with a decrease in oocyte depletion in mice receiving cyclophosphamide". Kyoto University, 2009. http://hdl.handle.net/2433/126421.
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Béthoux, François. "Essai therapeutique de cylcophosphamide dans la maladie de charcot". Lyon 1, 1990. http://www.theses.fr/1990LYO1M313.
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TSTE, WOON YUEN KHEE KIM. "Cancer du sein : chimiotherapie adjuvante ; resultats a long terme d'une serie de patientes n+ traitees de 1978 a 1992 a la clinique sainte-catherine par cmf ou avcf adjuvant". Aix-Marseille 2, 1993. http://www.theses.fr/1993AIX20143.
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Guenther, Michael. "Cancer Therapy with Metronomically Scheduled Cyclophosphamide: Experimental Modalities within GDEPT and Tumor Escape Mechanisms". Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-68423.
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Grenier, Lisanne. "The effects of paternal exposure to cyclophosphamide on the development of cleavage stage embryos". Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110358.
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Abnormal embryonic development can arise from maternal or paternal exposure to therapeutic agents, environmental toxicants or social habits. Such exposures prior to conception may damage the gametes and have detrimental effects on the developing embryo. When male rats are exposed to the chemotherapeutic agent, cyclophosphamide, the genomic integrity of the male germ cells is altered. The goals of these studies were to determine the impact of paternal preconceptional exposure to cyclophosphamide on embryonic development and to elucidate how cleavage stage embryos respond to DNA damage in the male genome. Paternal exposure to cyclophosphamide induces sperm DNA damage and leads to the alteration of chromatin compaction during spermiogenesis. Exposure to cyclophosphamide alters the rate of sperm decondensation, as manifested by the difference in the number of zygotes within each sperm decondensation stage compared to controls. DNA double strand breaks, detected by gamma H2AX small and large foci, are enhanced during sperm decondensation, indicative of chromatin remodelling and DNA damage recognition, respectively. The damaged male genome leads to the formation of micronuclei during the first zygotic division and to a gradual developmental delay in cleavage stage embryos. The capacity of cleavage stage embryos to mount an efficient DNA damage response against the damaged male genome prevents the propagation of DNA damage to all blastomeres in subsequent cellular divisions. The activation of DNA damage responses was inappropriate, as indicated by a decrease in PARylation, in the presence of an accumulation of DNA damage in the form of large gamma H2AX foci in eight-cell embryos sired by cyclophosphamide exposed males. Thus, DNA damage induced by paternal cyclophosphamide exposure is transmitted to the early embryo, altering the progression of developmental events and activating DNA damage responses that are likely to determine embryonic fate. Furthermore, the assessment of the quality of cleavage stage embryos and developmental competence with biomarkers of the DNA damage response, such as gamma H2AX foci and PAR polymers, may be useful in developmental medicine and infertility clinics.Un développement embryonnaire anormal peut être induit par l'exposition maternelle ou paternelle à des produits thérapeutiques, à des produits toxiques présents dans l'environnement ou à des habitudes sociales néfastes. De telles expositions peuvent endommager les gamètes mâtures et avoir des conséquences néfastes sur le développement embryonnaire. Lorsque des rats mâles sont exposés à un agent anticancéreux, la cyclophosphamide, l'intégrité des cellules germinales mâles est modifiée. Le but de ces études était de déterminer les conséquences d'un génome mâle endommagé par la cyclophosphamide sur le développement et les mécanismes de reconnaissance de l'ADN modifié dans des embryons au stade de division cellulaire rapide. L'exposition paternelle à la cyclophosphamide altère l'ADN et la condensation de la chromatine du spermatozoïde durant la spermatogénèse. Par conséquent la progression du spermatozoïde suivant la fertilisation durant les différents stades de la décondensation de la chromatine est affectée puisque les nombres de zygotes observés à chaque stade de décondensation étaient différents entre le groupe contrôle et celui soumis au traitement. Le nombre de cassures de l'ADN double-brin détectées par la méthode de comptage des petits et grands focis gamma H2AX est augmenté dans le groupe traité aussitôt que la chromatine commence à être décondensée dans les spermatozoïdes, démontrant ainsi un remodelage chromatinien et une altération de l'ADN, respectivement. Lors de la première division du zygote, nous avons observé la formation de micro-noyaux provoquant un retard du développement embryonnaire au stade de division cellulaire rapide. La capacité des embryons à induire une réponse appropriée aux dommages causés à l'ADN des spermatozoïdes durant ces stades de divisions rapides prévient la propagation des dommages à l'ADN d'un blastomère à un autre durant les subséquentes divisions. Les mécanismes de défense normalement activés dans les embryons sont inefficaces puisque le niveau de PARylation ne refléte pas la quantité des dommages causés à l'ADN des spermatozoïdes, tels que démontré par l'accumulation de grands focis gamma H2AX, dans les embryons à huit cellules fertilisés par des mâles exposés à la cyclophosphamide. Ces résultats démontrent que les dommages à l'ADN causés par l'exposition paternelle à la cyclophosphamide sont transmis aux embryons ayant des conséquences néfastes sur la progression du développement embryonnaire et l'activation des mécanismes de défenses affectant ainsi leur survie. L'analyse d'embryons au stade de division rapide ainsi que l'utilisation des marqueurs gamma H2AX et PAR polymère comme marqueurs de qualité embryonnaire et compétence du développement s'avèrent potentiellement utiles dans le domaine de la médecine du développement et en cliniques de fertilité.
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Aguilar, Adriana. "Stress response mechanisms during rat spermatogenesis and the effects of the anticancer agent cyclophosphamide". Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85111.
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Exposure of males to drugs or environmental chemicals can alter reproductive health and affect progeny outcome. The quality of the male germ cell is determined in part by the presence and function of stress response mechanisms. During spermatogenesis, different germ cell types display differential susceptibility to toxicants, suggesting there is variation in the presence and function of stress response mechanisms. Exposure of male rats to cyclophosphamide, a commonly used anticancer and immunosuppressive drug, alters male fertility and progeny outcome in a male-germ cell phase specific manner. The hypothesis of this thesis is that stress response mechanisms are differentially expressed during rat spermatogenesis and that their expression is involved in the response to the alkylating agent cyclophosphamide. The first objective of this thesis was to elucidate the expression of stress response genes at different stages of male germ cell development. Using cDNA arrays, the expression of several gene families was profiled in rat pachytene spermatocytes, round spermatids and elongating spermatids. Stress response genes were found to be differentially expressed during spermatogenesis. The second objective was to determine whether the expression of stress response genes was modified by exposure to cyclophosphamide. Acute and chronic cyclophosphamide treatment altered gene expression in a cell- and treatment-specific manner. Due to the known deleterious effects of cyclophosphamide on meiotic events, the last goal was to assess the ability of pachytene spermatocytes to undergo the meiotic G21/M transition. The delayed meiotic progression induced by acute cyclophosphamide treatment, likely to be a checkpoint response, contrasted with the lack of delay after chronic drug exposure. Together these results show that male germ cells are differentially equipped with mechanisms of stress response. Furthermore, cyclophosphamide alters the expression of stres
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Viaud, Sophie. "Etude des effets du cyclophosphamide sur l’immunité anti-tumorale : relations avec le microbiote intestinal". Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T064.
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Les chimiothérapies conventionnelles anticancéreuses ont été développées dans le but de traiter le cancer par élimination directe et/ou par inhibition de croissance les cellules tumorales en division. Les cellules endothéliales en prolifération à l’origine de la vascularisation intra-tumorale sont également connues pour être sensibles aux effets cytotoxiques des agents anticancéreux. Depuis, de nombreuses études ont montré que certaines thérapies conventionnelles peuvent être exploitées pour leurs capacités anti-angiogéniques (Browder et al. Cancer Research 2000). La stratégie mise en place consiste à suivre des protocoles où la thérapie est administrée à des doses faibles non myéloablatives et plus fréquemment que les thérapies conventionnelles, appelés dosages métronomiques (Hanahan et al. JCI 2000, Gasparini et al. Lancet Oncology 2001). Le cyclophosphamide (CTX) est un agent alkylant communément utilisé en chimiothérapie dans des protocoles à dosage métronomique. Dans les années 1980, 2 études ont montré que le CTX utilisé à dose métronomique pouvait avoir aussi un rôle sur l’immunité en réduisant la fonction suppressive d’une population de lymphocytes T CD4+ dans un modèle expérimental de tumeur (Awwad et al. Cancer Research 1989) et chez des patients atteints de cancer (Berd et al. Cancer Research 1987). Depuis, les connaissances ont progressé et à présent le CTX métronomique est reconnu pour pouvoir limiter l’expansion et les fonctions des lymphocytes T régulateurs (Treg) (Ghiringhelli et al. EJI 2004, Lutsiak et al. Blood 2005) conduisant à une polarisation des cellules T auxiliaires vers un profil Th1 (Matar et al. Eur J cancer 2000 et Cancer Immunol Immunother 2002). Utilisé en association, le CTX métronomique s’avère donc être un outil intéressant dans le traitement anticancéreux (Hermans et al. Cancer Research 2003, Taieb et al. JI 2006). Nos résultats montrent l’importance des lymphocytes T CD4+ sécréteurs d’IL-17 et d’IFNg dans les effets du CTXConventional cancer chemotherapies were developed to target cancer cells either by directly eliminating them or by inhibiting the growth of dividing tumor cells. Proliferating endothelial cells at the origin of intratumoral vascularization are known to be sensitive to the cytotoxic effects of antineoplastic agents. Many studies have shown that some conventional therapies can be exploited for their anti-angiogenic capabilities (Browder et al. Cancer Research 2000). The adopted strategy, called metronomic chemotherapy, consists of administering low doses of drug that do not induce myelosuppression, on a more frequent schedule as compared to conventional therapies (Hanahan et al. JCI 2000, Gasparini et al. Lancet Oncology 2001). Cyclophosphamide (CTX) is an alkylating agent commonly used as a metronomic chemotherapy. In the 1980s, two studies demonstrated that when used at a metronomic dosing, CTX could impact the immune response particularly in reducing the suppressive function of a CD4+ T lymphocyte population in an experimental tumour model (Awwad et al. Cancer Research 1989) and in cancer patients (Berd et al. Cancer Research 1987). Since then, knowledge has evolved and now CTX used as a metronomic or low-dose therapy is administered to limit expansion and functions of regulatory T cells (Treg) (Ghiringhelli et al. EJI 2004, Lutsiak et al. Blood 2005), leading to a helper T cell polarization toward a Th1 profile (Matar et al. Eur J cancer 2000 et Cancer Immunol Immunother 2002). When used in combination, CTX turns out to be a potent drug in the antineoplastic treatments armamentarium (Hermans et al. Cancer Research 2003, Taieb et al. JI 2006). Our results demonstrate the importance of CTX effects on IL-17 and IFNg secreting CD4+ T lymphocytes
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Morozova, O. M. "Features of the reyer's patches small intestine of the immature rats after cyclophosphamide ingection". Thesis, Сумський державний університет, 2013. http://essuir.sumdu.edu.ua/handle/123456789/31968.
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Peyer's patches of the small intestine is one of the first barrier against antigens in the human body. They are dynamic systems, and actively respond to external and internal factors. The aim of this study was to determine the effect of cyclophosphamide on the structure of Peyer's patches of the small intestine of immature rats.The study was conducted on 36 albino immature male rats weighing 60-90 g.
When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/31968
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Meen, Murielle. "La cystite induite par le cyclophosphamide chez le rat : un nouveau modele comportemental de douleur viscerale.aspects methodologiques,physiopathologiques et pharmacologiques (doctorat)". Clermont-Ferrand 1, 2001. http://www.theses.fr/2001CLF1PP07.
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Liang, Lijin. "Prevention of cyclophosphamide-accelerated diabetes in NOD mice with the phosphodiesterase inhibitors Pentoxifylline and Rolipram". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0023/MQ50821.pdf.
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Harrouk, Wafa A. "Consequences of paternal exposure to the anti-cancer drug, cyclophosphamide, on rat pre-implantation development". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0029/NQ64572.pdf.
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Troster, Charles Micah Smolkin. "Trace analysis of cyclophosphamide and its metabolites in urine by liquid chromatography-tandem mass spectrometry". Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/29263.
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Cyclophosphamide (CP) is an antineoplastic drug used to treat a wide variety of cancers and immune disorders. CP is also a highly toxic alkylating agent, classified as an IARC Group 1 carcinogen. Workers in health-care environments are vulnerable to occupational exposure to CP, primarily via inhalation and dermal absorption. CP is a prodrug; both its therapeutic effectiveness and toxicity are activated through metabolism. To date, however, no study measuring occupational exposure to CP has successfully analyzed its metabolites. The main objective of this work was to develop an analytical method for CP, as well as its metabolites 4-ketocyclophosphamide (KCP) and carboxyphosphamide (CBP), in urine samples collected from health-care workers at risk of CP exposure.
A liquid chromatography-tandem mass spectrometry (LC/MS-MS) method was optimized for CP, KCP and CBP on two different instruments. Post-column infusion showed that the matrix effects resulting from synthetic urine could be separated from the analyte peaks by LC. Estimated instrument limits of quantitation for CP, KCP and CBP in neat solvent were respectively 4.2, 8.2 and 57 ng/L. These parameters were sufficient to meet a quantitation target of 50 ng/L CP in urine, but suggested a need to reduce sample volume to reach a 2.5 ng/L target for KCP and CBP.
Solid-phase extraction (SPE) was explored as a means to exchange the sample matrix for clean solvent and reduce sample volume. Previously developed SPE methods for CP were not designed to include the more polar metabolites, and thus required modification. The best retention of metabolites was seen on a C¹⁸ sorbent with reduced carbon loading. Retention was improved further under acidic loading conditions, but this had to be controlled carefully since CBP can decompose more rapidly at acidic pH. All three analytes were observed to elute with methanol.
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Liang, Lijin 1966. "Prevention of cyclophosphamide-accelerated diabetes in NOD mice with the phosphodiesterase inhibitors Pentoxifylinne and Rolipram". Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=21594.
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Interleukin (IL)-12, interferon (IFN)-gamma, and other inflammatory cytokines play an important role in the pathogenesis of autoimmune insulitis and diabetes in NOD mice, and inhibition of these cytokines is likely to be beneficial. In this study, we found that Pentoxifylline (PTX) and Rolipram (phosphodiesterase [PDE] inhibitors that induce increased intracellular cAMP) can block inflammatory cytokine production. Inhibition of IL-12 and IFN-gamma secretion was demonstrated in macrophages activated with lipopolysaccharide or T-cells stimulated through the CD3/T-cell receptor complex, respectively. Moreover, strong inhibition of IL-12 was demonstrated in vivo in superantigen-immunized mice. Rolipram was inhibitory at concentrations as low as 10-8 to 10-7 mol/l, and on molar basis, it was 100-fold more effective than PTX. Tumor necrosis factor (TNF)-alpha was also inhibited, but IL-4 was less sensitive to suppression. In NOD mice, both PTX and Rolipram reduced the severity of insulitis and prevented cyclophosphamide-accelerated diabetes. It appears that blocking the activity of type IV PDE is sufficient to mediate the effects reported in this study, since Rolipram inhibits only this isoform, unlike PTX (a general inhibitor).Significance. PTX and Rolipram may be effective in the treatment of autoimmune diabetes or other conditions characterized by excessive production of inflammatory cytokines.
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Harrouk, Wafa. "Consequences of paternal exposure to the anti-cancer drug, cyclophosphamide, on rat pre-implantation development". Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36604.
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Administration of cyclophosphamide to males targets the germ cells and causes DNA damage including single strand breaks and DNA-DNA cross links. When males are treated with a chronic low dose of cyclophosphamide and then mated to normal females, progeny loss is manifested at the pre- and post-implantation stages of development. The earliest events that lead to embryonic loss were traced to day 2 of gestation when embryos had a decreased DNA synthesis profile and lower cell numbers than control litters. I investigated the hypothesis that chronic exposure of male rats to cyclophosphamide alters zygotic gene expression thus leading to embryonic loss. To assess DNA damage in the embryo, the Comet Assay was performed on 1-cell stage embryos. A significant number of embryos sired by cyclophosphamide-treated males showed the appearance of the Comet indicative of the effect of damaged sperm on the embryos starting from the 1-cell stage. Using a candidate gene approach, the antisense RNA (aRNA), I described the presence of several DNA repair gene families in normal embryos. Progeny sired by cyclophosphamide-treated males manifested a differential expression profile for several of these genes when compared to controls, suggestive of the ability of the embryo to respond to damaged sperm through the major DNA repair systems. To study the functional capacity of progeny sired by cyclophosphamide-treated males, I assessed total RNA synthesis in both groups; while control litters showed a peak of RNA synthesis at the 4-cell stage, the treatment group showed constant low expression throughout the stages examined. I mapped the profile of a number of gene families whose roles are essential for early development in both control and cyclophosphamide-treated groups. While control embryos showed a peak of expression for the majority of genes at the 8-cell stage, that of the cyclophosphamide-group showed an early induction at the 2-cell stage, indicative of loss of the tightly regulated