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Literatura científica selecionada sobre o tema "MitoTALEN"

Autor: Grafiati

Publicado: 31 de agosto de 2024

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Artigos de revistas sobre o assunto "MitoTALEN"

Omukai, Shiho, Shin-ich Arimura, Kinya Toriyama e Tomohiko Kazama. "Disruption of mitochondrial open reading frame 352 partially restores pollen development in cytoplasmic male sterile rice". Plant Physiology 187, n.º 1 (20 de maio de 2021): 236–46. http://dx.doi.org/10.1093/plphys/kiab236.

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Abstract Plant mitochondrial genomes sometimes carry cytoplasmic male sterility (CMS)-associated genes. These genes have been harnessed in various crops to produce high-yielding F1 hybrid seeds. The gene open reading frame 352 (orf352) was reported to be an RT102-type CMS gene in rice (Oryza sativa), although the mechanism underlying its role in CMS is unknown. Here, we employed mitochondrion-targeted transcription activator-like effector nucleases (mitoTALENs) to knockout orf352 from the mitochondrial genome in the CMS rice RT102A. We isolated 18 independent transformation events in RT102A that resulted in genome editing of orf352, including its complete removal from the mitochondrial genome in several plants. Sequence analysis around the mitoTALEN target sites revealed their induced double-strand breaks were repaired via homologous recombination. Near the 5ʹ-target site, repair involved sequences identical to orf284, while repair of the 3ʹ-target site yielded various new sequences that generated chimeric genes consisting of orf352 fragments. Plants with a chimeric mitochondrial gene encoding amino acids 179–352 of ORF352 exhibited the same shrunken pollen grain phenotype as RT102A, whereas plants either lacking orf352 or harboring a chimeric gene encoding amino acids 211–352 of ORF352 exhibited partial rescue of pollen viability and germination, although these plants failed to set seed. These results demonstrated that disruption of orf352 partially restored pollen development, indicating that amino acids 179–210 from ORF352 may contribute to pollen abortion.

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Hashimoto, Masami, Sandra R. Bacman, Susana Peralta, Marni J. Falk, Anne Chomyn, David C. Chan, Sion L. Williams e Carlos T. Moraes. "MitoTALEN: A General Approach to Reduce Mutant mtDNA Loads and Restore Oxidative Phosphorylation Function in Mitochondrial Diseases". Molecular Therapy 23, n.º 10 (outubro de 2015): 1592–99. http://dx.doi.org/10.1038/mt.2015.126.

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Bacman, Sandra R., Johanna H. K. Kauppila, Claudia V. Pereira, Nadee Nissanka, Maria Miranda, Milena Pinto, Sion L. Williams, Nils-Göran Larsson, James B. Stewart e Carlos T. Moraes. "MitoTALEN reduces mutant mtDNA load and restores tRNAAla levels in a mouse model of heteroplasmic mtDNA mutation". Nature Medicine 24, n.º 11 (24 de setembro de 2018): 1696–700. http://dx.doi.org/10.1038/s41591-018-0166-8.

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Bacman, Sandra R., Johanna H. K. Kauppila, Claudia V. Pereira, Nadee Nissanka, Maria Miranda, Milena Pinto, Sion L. Williams, Nils-Göran Larsson, James B. Stewart e Carlos T. Moraes. "Author Correction: MitoTALEN reduces mutant mtDNA load and restores tRNAAla levels in a mouse model of heteroplasmic mtDNA mutation". Nature Medicine 24, n.º 12 (5 de outubro de 2018): 1940. http://dx.doi.org/10.1038/s41591-018-0234-0.

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Yashina, D. P., e Z. A. Afanasieva. "Experience of mitotane successful in the treatment of metastatic adrenocortical cancer". Endocrine Surgery 15, n.º 4 (14 de dezembro de 2022): 12–13. http://dx.doi.org/10.14341/serg12764.

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Background. Adrenocortical cancer (ACC) is a rare malignant endocrine tumor endowed with an aggressive biological potential and a poor prognosis. Surgical adrenalectomy remains the only radical treatment for local ACC. The overall 5-year survival rate of stages with local ACC varies from 56% to 96% and depends on the level of surgical training of a specialized center and the use of adjuvant therapy. Mitotan is the only approved chemotherapeutic agent for the adjuvant treatment of both the primary tumor and relapse and metastases.Aim. To evaluate the experience of mitotane successful use in a young patient with recurrent ACC using the experience of a large medical institution.Clinical observation. Patient R., 31 years old, is under dispensary observation for recurrent adrenocortical cancer of the left adrenal gland T1N0M0 stage 1, class 3. Progression from 2015, 2017, February 2019, April 2019, September 2020 (in the bed, MTS to the left kidney, MTS to the retroperitoneal tissue, MTS to the soft tissues of the lumbar region on the left, MTS to the lungs). Eradication of the tumor tissue was performed surgically, followed by morphological confirmation of the removed foci. For the first time, the diagnosis was established at the age of 23 during an examination for Itsenko-Cushing’s syndrome. Morphologically, the diagnosis of ACC was established after a histological examination of the tumor biopsy obtained by left-sided adrenalectomy (adrenocortical cancer, ki67 up to 20%).During a scheduled dispensary examination in September 2020, according to CT scan of the chest with contrast, two foci were identified in the right lung: in C1 — 10 * 15 mm, in C2 — 30 * 21 mm. By decision of the council (consisting of an oncologist-endocrinologist, a thoracic surgeon and a chemotherapist), a decision was made to prescribe mitotane with dose titration under the control of the level of mitotane in the blood until it reaches 14–20 ng/l, without morphological examination of the foci. Hypocorticism was corrected by the simultaneous use of hydrocortisone with mitotane at a dose of 20 mg per day under the control of ACTH levels. In X-ray evaluation by CT of the chest with a frequency of 3 months, the therapeutic effect in the form of a decrease in the size of the foci (RESIST1.1) occurred in the first 3 months. Mitotan was canceled in November 2021 after complete regression of tumor foci according to CT scan of the chest (pneumosclerosis areas 10*4 mm). Currently, the patient is receiving hormone replacement therapy with hydrocortisone 25 mg per day and is under dispensary observation.Conclusion. Clinical observation has demonstrated the successful use of mitotane in the treatment of metastatic adrenocortical cancer.

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Sava, Alexandra Daniela, Tiberiu Bogdan Szekely, Cornelia Togănel, Adela Vacar e Simona Gurzu. "Adrenocortical carcinoma: A tumor with poor answer to classic chemotherapy". Acta Marisiensis - Seria Medica 69, n.º 4 (1 de dezembro de 2023): 292–94. http://dx.doi.org/10.2478/amma-2023-0039.

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Abstract Introduction: Adrenocortical carcinoma (ACC) represents a rare endocrine malignancy being the second most aggressive endocrine cancer after anaplastic thyroid cancer. [1]. While most of them arise sporadically, up to 15% of adult ACC patients are related to germline mutations associated with familial cancer syndromes.[1,2]. Current treatment strategies include surgery as well as systemic therapy with mitotane and chemotherapy. Case report: A 60-year-old female patient with a family history of colon cancer, multinodular goiter, hypothyroidism treated with substitutive therapy, uterine fibroids, and hypertension, was diagnosed with adrenocortical carcinoma. No distant metastasis were present at the moment of diagnosis so an adrenalectomy was performed. Due to postoperative complications, a total nephrectomy was also needed. Adjuvant Mitotane treatment was given. A CT exam performed 5 months after the resection showed multiple pulmonary metastasis, a liver nodule and peritoneal carcinomatosis. The standard first-line chemotherapy of choice was Carboplatin and Etoposide. After completing 3 cycles of chemotherapy the imaging reassessment show the progression of liver and peritoneal lesions and the quasi-complete regression of lung lesions. Currently, the Mitotate treatment was stopped due to severe adverse reactions. Conclusions: Adrenocortical carcinoma is a rare endocrine malignancy with a poor prognosis. The recruitment of ACC patients for new clinical trials to investigate new treatment strategies is needed because currently, no significant therapeutic breakthrough is emerging.

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&NA;. "Mitotane". Reactions Weekly &NA;, n.º 1385 (janeiro de 2012): 33. http://dx.doi.org/10.2165/00128415-201213850-00121.

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&NA;. "Mitotane". Reactions Weekly &NA;, n.º 1180 (dezembro de 2007): 28. http://dx.doi.org/10.2165/00128415-200711800-00084.

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&NA;. "Mitotane". Reactions Weekly &NA;, n.º 1155 (junho de 2007): 14. http://dx.doi.org/10.2165/00128415-200711550-00039.

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&NA;. "Mitotane". Reactions Weekly &NA;, n.º 1399 (abril de 2012): 23. http://dx.doi.org/10.2165/00128415-201213990-00084.

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Mais fontes

Teses / dissertações sobre o assunto "MitoTALEN"

Kubilinskas, Rokas. "MitoTALENs to explore mitochondrial DNA repair and segregation". Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ014.

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Pendant longtemps, il n'était pas possible de manipuler le génome mitochondrial des plantes (mtDNA), jusqu'aux récentes avancées en édition des génomes utilisant des "Transcription Activator-Like Effector Nucleases" (TALEN). Dans ce travail, j'ai utilisé des TALENs spécifiquement ciblés sur les mitochondries (mitoTALENs) pour étudier la réparation et la ségrégation du mtDNA des plantes. Les constructions de mitoTALEN ont été introduites dans 10 lignées mutantes différentes d'Arabidopsis thaliana, déficientes en divers facteurs impliqués dans la réparation mitochondriale des plantes par recombinaison homologue. Les lignées résultantes ont eté analysées par séquençage Illumina et par des approches de qPCR. Chez les plantes de type sauvage, les cassures double brin (DSB) de l'ADN mitochondrial induites par les mitoTALENs ont été réparées par recombinaison homologue, entraînant le remplacement de la région contenant la DSB par une séquence distale, non-affectée, du mtDNA, flanquée par les mêmes séquences répétées. Chez les mutants déficients en facteurs de réparation, la réparation pourrait se dé placer vers des voies alternatives, telles que le "Single-Strand Annealing" (SSA) et "Microhomology-mediated recombination" (MHMR). De plus, chez certains mutants, les données n'ont révélé aucune trace de réparation des DSB, mais ont plutôt suggéré que les plantes déficientes en facteurs de réparation essentiels pourraient survivre en reconstituant un génome mitochondrial alternatif viable, à partir de sous- génomes pré existants se répliquant de manière autonome
For long, the plant mitochondrial genome (mtDNA) was not amenable to manipulation, until recent advancements in genome engineering using Transcription Activator-Like Effector Nucleases (TALEN). In this work I used TALENs specifically targeted to mitochondria (mitoTALENs) to study plant mtDNA repair and segregation. MitoTALEN constructs were transformed into the background of 10 different Arabidopsis thaliana mutant lines, deficient in various factors involved in plant mitochondrial repair by homologous recombination. The resulting lines were analysed by Illumina sequencing and qPCR approaches. In wild type plants, the mtDNA double-strand-break (DSB) induced by MitoTALENs was repaired by homologous recombination, resulting in the replacement of the region containing the DSB by a distal unaffected sequence of the mtDNA, flanked by the same set of repeated sequences. In mutants deficient in repair factors, repair could shift to alternative pathways, such as Single-Strand Annealing (SSA) and Microhomology-mediated recombination (MHMR). Furthermore, in some mutants, the data revealed no evidence of DSB repair, but rather suggested that plants deficient in key repair factors could survive by reconstituting an alternative viable mitochondrial genome, from pre-existing autonomously replicating sub-genomes

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Hescot, Ségolène. "Cibles moléculaires du Mitotane : Implications pour le traitement du corticosurrénalome". Thesis, Paris 11, 2015. http://www.theses.fr/2015PA11T040.

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Le mitotane, ou o,p’DDD, médicament historique dérivé d’un insecticide, reste le traitement de référence du corticosurrénalome (CS), tumeur rare et de mauvais pronostic. Le mitotane exerce un effet anti-sécrétoire associé à un effet anti-tumoral dont les mécanismes d’action sous-jacents sont mal compris et ses cibles moléculaires restent inconnues. Néanmoins, de nombreux arguments semblent désigner la mitochondrie comme organite cible du mitotane. Dans ce travail de thèse, nous nous sommes intéressés à l’impact mitochondrial du mitotane par des approches complémentaires sur plusieurs modèles expérimentaux. Nous avons ainsi pu mettre en évidence une inhibition sélective des complexes I et IV de la chaîne respiratoire, une fission du réseau mitochondrial ou encore une activation de la biogenèse mitochondriale. Ces données nous ont permis d’identifier les mitochondrial-associated membranes (MAM) et le transducéosome comme organites cibles du mitotane. Parallèlement, en réévaluant le rôle potentiel du métabolite acide o,p’DDA, nous avons pu exclure son implication dans l’action cytotoxique du mitotane. Nous avons également démontré que le mitotane libre, non lié aux lipoprotéines, était le plus actif in vitro et pouvait ainsi être celui responsable de l’action pharmacologique in vivo. L’ensemble de ces résultats apportent une meilleure compréhension des mécanismes d’action du mitotane et devrait permettre d’identifier des facteurs prédictifs de réponse à ce traitement pour une meilleure prise en charge des patients atteints de CS
Mitotane is o,p’DDD, an historic drug derived from an insecticide and represents the treatment of choice for adrenocortical carcinoma (ACC), a rare adrenal tumor associated with bad prognosis. Mitotane is responsible for an inhibition of steroidogenesis associated with an antitumoral effect but its exact molecular mechanisms of action remain unclear and its molecular target remains unknown. However, mitochondria could be an organite targeted by mitotane. In this study we evaluated mitochondrial impact of mitotane using complementary approaches on several experimental models. We showed a mitotane-induced selective inhibition of respiratory chain complexes I and IV, an increased fission of the mitochondrial network and an activation of the mitochondrial biogenesis. These data helped us to identify mitochondrial-associated membranes (MAM) and so-called transduceosome as targeted organites of mitotane. We also reevaluated the potential role of the acid metabolite o,p’DDA and excluded its implication in the cytotoxic action of mitotane. Finally, we demonstrated that free mitotane which is not linked to lipoproteins is more efficient in vitro and could be therefore responsible for pharmacological action in vivo. Altogether, these results allow to better understand mitotane mechanisms of action and should help to identify predictive markers of response to mitotane for a better care of patients with ACC

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GENTILIN, Erica. "Studio dell’azione del Mitotane, farmaco adrenolitico, sulla funzionalità ipofisaria". Doctoral thesis, Università degli studi di Ferrara, 2011. http://hdl.handle.net/11392/2388826.

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Mitotane (o,p_-DDD), a derivative of the insecticide dichlorodiphenyltrichloroethane, has been widely used for treatment of adrenocortical carcinoma (ACC). ACC is a rare neoplasm characterized by a dismal prognosis, with less than 50 % of patients surviving 5 yr after diagnosis. Because the majority of patients undergoing radical resection relapse, adjuvant therapy has been considered as an option. Indeed, it has been shown that adjuvant mitotane treatment has beneficial effects on outcome in ACC patients. Over the years, mitotane therapy has been thoroughly debated because of its toxicity that limited patient compliance and possibly drug efficacy, due to the previously employed high doses without blood concentration monitoring. The important advancement represented by mitotane monitoring allowed to demonstrate that mitotane activity and toxicity is correlated with the achieved blood drug concentrations. However, the undesired effects of mitotane also manifest at concentrations considered to have a therapeutic impact (14–20 mg/liter, corresponding to 44–62 microM), representing a major hurdle to treat adjuvantly patients who are free of disease after radical surgery. Mitotane treatment is associated with several adverse events. Recently, the effects of mitotane on the endocrine system have been thoroughly investigated in patients treated adjunctively after complete ACC removal, where perturbation in thyroid function is characterized by a decrease in FT4 levels over time, inversely correlated with mitotane concentration. Free T3 (FT3) and TSH levels do not change significantly, mimicking central hypothyroidism. Previously, mitotane has been demonstrated to increase T4-binding globulin (TBG) and to compete with T4 for TBG binding sites, but these phenomena do not explain the changes in thyroid function pattern observed during adjuvant therapy. It has been suggested that mitotane might impair pituitary TSH secretion, interfere with FT3, FT4, and/or TSH assays, or affect deiodase activity, thus changing the FT4/FT3 ratio. However, no evidence is currently available to support these hypotheses. Additionally, reduced ACTH levels were observed in patients treated adiuvantly with mitotane. The aim of our study was to investigate whether mitotane may interfere with thyroid hormone and TSH assays in human serum or directly affect TSH secretion in a mouse model of thyrotrope cells. Additionally, the aim of this study was to evaluate mitotane effects on adrenocorticotrope function and ACTH secretion in a mouse model of adrenocorticotrope cells, in order to explain the perturbation of ACTH levels in patients treated adiuvantly with mitotane. Our results demonstrate that mitotane does not interfere with thyroid hormone laboratory tests but directly reduces both secretory activity and cell viability on pituitary TSH secreting mouse cells. These data represent a possible explanation of the biochemical picture consistent with central hypothyroidism in patients undergoing mitotane therapy and open new perspectives on the direct pituitary effects of this drug. Moreover, mitotane inhibits adrenocorticotrope cell viability, inducing apoptotic mechanisms, and reduces ACTH secretion, both basally and after CRH stimulation. These results suggest that mitotane profoundly affect pituitary function, probably without cell specificity.

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Attivi, David. "Mise en forme et amélioration de la biodisponibilité d'un anticancéreux destiné à la voie orale : exemple du mitotane". Thesis, Nancy 1, 2010. http://www.theses.fr/2010NAN10022/document.

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Le mitotane ou o,p'-DDD est un dérivé organochloré très peu soluble dans l'eau. Il est utilisé dans le traitement du cancer corticosurrénalien métastasé ou inopérable (Lysodren®). En thérapeutique, il est nécessaire d'utiliser de fortes doses pour atteindre généralement au bout de trois mois, la mitotanémie efficace. Cela entraine le plus souvent, des effets indésirables gastroduodénaux et neuromusculaires, qui rendent les patients très peu compliants.L'objectif principal de cette thèse est de mettre au point, d'évaluer et de comparer les différentes formulations de mitotane afin d'améliorer la biodisponibilité du mitotane par rapport à la forme conventionnelle Lysodren®. Dans cette optique, le but recherché en clinique humaine serait de concevoir une forme galénique pouvant permettre d'utiliser de faibles doses journalières afin d'éviter les effets indésirables liés à la toxicité cumulative du mitotane. Pour cela, dans le but d'augmenter sa solubilité et de le rendre plus biodisponible, nous avons encapsulé le mitotane sous formes de particules polymériques et de microémulsions.Nous avons préparé des nanocapsules à partir de polymères biodégradables (la poly-epsilon-caprolactone) (PCL) et d'une association de PCL et de polymères non biodégradables (L'Eudragit® RL). Nous avons également préparé des microparticules de PCL et des systèmes autoémulsionnants ou SMEDDS.L'évaluation des caractéristiques physico-chimiques des particules montre des diamètres de 300 nm pour les nanocapsules et pour les microparticules, des diamètres variant de 40 à 76 µm. Le potentiel zêta est négatif pour les particules de PCL et positif pour celles associant les polymères PCL et RL. Pour les microémulsions, les diagrammes pseudoternaires ont permis le choix d'une association comportant du Capryol®, Tween® 20 et Crémophor® EL (33, 33, 33%). Les microémulsions ont un diamètre d'environ 40 nm. Les profils de libération in vitro du mitotane montrent une cinétique rapide et une quantité de mitotane libérée plus importante pour les microémulsions et les formes particulaires par rapport à la forme conventionnelle Lysodren®.De même, la réalisation de la pharmacocinétique à dose unique de 100 mg/kg chez des lapins montre des biodisponibilités relatives de 339% plus importantes pour les microémulsions, 195% pour les nanocapsules et 187% pour les microparticules. La quantification du mitotane absorbé dans des modèles Caco-2 montre une absorption complète du mitotane au bout de 4h lorsque le mitotane est formulé sous forme de microémulsions. Pour les microparticules et les nanocapsules, 50 et 45% de la dose initiale ont été respectivement absorbées par les cellules Caco-2. Cette évaluation sur le modèle Caco-2 a également confirmé le faible taux de passage de la poudre de mitotane (10%). Enfin, la réalisation des études de passage sur des coupes de jéjunum de rat en chambre de Ussing confirme que la quantité de mitotane qui a diffusé à travers la membrane jéjunale à partir des microémulsions est 5 fois supérieure à celle obtenue à partir de la poudre de mitotane.En conclusion, les microémulsions présentent un intérêt comme forme orale pour améliorer la biodisponibilité du mitotane. Elles ont pour avantage de multiplier la biodisponibilité par un facteur 3 chez le lapin et sont de fabrication peu coûteuse. Elles constituent une réelle alternative à la forme conventionnelle Lysodren® disponible actuellement sur le marché européen
Mitotane or o, p'-DDD is a organochlorine drug, very slightly soluble in water. It is used in the treatment of non resectable and metastasized adrenocortical carcinoma (Lysodren®). In therapy, to achieve therapeutic plasma level, high cumulative doses of mitotane were usually used during 3-5 months. This regimen causes gastrointestinal and neuromuscular side effects and make patients to be less compliants.The main objective of this work is to developp differents formulations of mitotane in order to improve the relative bioavailability when compared with conventional form Lysodren®. To shorten this equilibration time and reduce side effects, it's necessary to develop a new formulation. In order to increase mitotane solubility and make it more bioavailable, we encapsulated mitotane in polymeric particles and microemulsions.We prepared nanocapsules with biodegradable polymers (poly-epsilon-caprolactone) (PCL) and an association of PCL and non-biodegradable polymers (Eudragit®RL). We have also prepared PCL microparticles and a Self Microemulsifying Drug Delivery System or SMEDDS.Nanocapsules and microparticles diameters were respectively 300 nm and 40 to 76 µm. The zeta potential is negative for PCL particles wheras particles combining PCL and Eudragit®RL polymers exhibited positive zêta potential. For microemulsions, we investigated by constructing ternary phase diagrams and choosing the optimal formulation consisted of a mixture of Capryol®, Tween® 20 and Cremophor® EL (33, 33, 33%) with an emulsion diameter of 40 nm. The release of mitotane from SMEDDS and particles was higher and faster than from the conventional form Lysodren®.Pharmacokinetics after single-dose of oral mitotane formulations (100 mg/kg) in rabbits showed a 339% increase of relative bioavailability with microemulsions, 195% with the nanocapsules and 187% with the microparticles. Caco-2 cell culture showed a complete absorption of mitotane after 4h with microemulsions. For microparticles and nanocapsules, 50 and 45% of the initial dose, were respectively absorbed by Caco-2 cells. Caco-2 cells evaluation confirmed the low absorption of the mitotane powder (10%). Finally, Ussing chamber showed that microemulsions pass through the intestinal barrier 5 times higher than a solution of mitotane. In conclusion, microemulsions showed improvement of bioavailability of mitotane by a factor 3 in rabbits and could allow cost effective production. Microemulsions are a real alternative to Lysodren® which is currently available on the European market

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Jacobi, Janin Melanie Katharina [Verfasser], e Florian [Akademischer Betreuer] Lang. "Zelltod humaner Erythrozyten durch Mitotan und Miltefosin / Janin Melanie Katharina Jacobi ; Betreuer: Florian Lang". Tübingen : Universitätsbibliothek Tübingen, 2018. http://d-nb.info/1196704031/34.

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BENSAID, JEAN-JACQUES. "Insuffisance surrenale definitive induite par op'ddd dans le syndrome de cushing : a propos de 4 observations". Lille 2, 1992. http://www.theses.fr/1992LIL2M256.

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Wiemer, Laura Elisa [Verfasser], Martin [Gutachter] Fassnacht e Andreas [Gutachter] Rosenwald. "In-vitro-Untersuchungen zur molekularen Wirkung von Mitotane beim Nebennierenrindenkarzinom / Laura Elisa Wiemer. Gutachter: Martin Fassnacht ; Andreas Rosenwald". Würzburg : Universität Würzburg, 2013. http://d-nb.info/1102823414/34.

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Santos, Inês Carreira dos. "Clínica e cirurgia de animais de companhia". Master's thesis, Universidade de Évora, 2018. http://hdl.handle.net/10174/23096.

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Este relatório foi realizado no âmbito do estágio do MIMV da Universidade de Évora que decorreu no Hospital Veterinário da Associação Zoófila Portuguesa. A primeira parte é relativa à casuística acompanhada durante o estágio. A área da clínica médica onde foram observadas mais ocorrências foi a gastroenterologia. A segunda parte aborda uma revisão bibliográfica do tema “hiperadrenocorticismo canino” sendo complementada com um caso clíni-co que foi acompanhado durante o estágio. O hiperadrenocorticismo é provocado pela produção ou administração excessiva de gluco-corticoides. Os sinais clínicos incluem polidipsia, poliúria, polifagia, alopécia simétrica bilateral, abdómen pendular e hepatomegália. Esta síndrome pode ser iatrogénica ou espontânea. O diagnóstico é muito importante para diferenciar a causa de hiperadrenocorticismo, que é es-sencial para o tratamento. Este pode ser cirúrgico ou médico, sendo que os fármacos mais utilizados são o trilostano e o mitotano; Abstract: Clinic and surgery of small animals This report was carried out as part of the curricular traineeship at the Hospital Veter-inário da Associação Zoófila Portuguesa. The first part is related to the clinical cases followed during the training. The area of the medical clinic where most occurrences were observed was gastroenterology. In the second part a bibliographic review is made of the theme "canine hyper-adrenocorticism", complemented with a clinical case that was followed during the referred train-ing. Hyperadrenocorticism is caused by the excessive production or administration of gluco-corticoids. The clinical signs include polydipsia, polyuria, polyphagia, symmetrical bilateral alo-pecia, pot-bellied appearance and hepatomegaly. This syndrome can be iatrogenic or sponta-neous. Diagnosis is very important to differentiate a cause of hyperadrenocorticism, which is essential for treatment. The treatment can be surgical or medical, and the most used drugs are trilostane and mitotane.

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Dias, Raquel Macedo. "Separação cromatografica quiral do o,p'-diclorodifenildicloroetano (mitotano) em fase estacionaria quiral O,O'bis[4-terc-butilbenzoil]-N,N'dialil-L-tartadiamida". [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/266169.

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Orientador: Cesar Costapinto Santana
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Quimica
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Resumo: O mitotano (o,p?-diclorodifenildicloroetano) é um fármaco utilizado no tratamento de carcinoma adrenocortical. Ele é comercializado na forma racêmica, ou seja, na proporção 1:1 dos seus enantiômeros R e S. A influência da quiralidade da molécula sobre seu efeito farmacológico ainda não foi estudada. Portanto, a separação dos enantiômeros é importante para testes biológicos comparativos de efeitos colaterais. Este trabalho foi desenvolvido com o intuito de estudar a separação deste fármaco pela técnica de cromatografia líquida de alta eficiência utilizando coluna recheada com a fase estacionária quiral O,O?-bis[4-tercbutilbenzoil]-N,N?-dialil-L-tartardiamida. Diferentes combinações de fase móvel foram testadas e os melhores resultados foram obtidos com hexano/acetato de etila na proporção 95/5 (v/v). Experimentos de pulsos com soluções diluídas do traçador e dos enantiômeros do mitotano foram realizados variando a vazão de fase móvel e a temperatura do sistema. Foram determinados as porosidades do sistema, os parâmetros cromatográficos, os dados de equilíbrio, coeficientes de dispersão axial e parâmetros de transferência de massa. Os resultados mostraram separação satisfatória, com número de pratos superando 9000 e fatores de separação na ordem de 1,13. Os valores dos coeficientes de Henry foram maiores que a unidade para ambos os enantiômeros, sendo que o enantiômero mais retido R-(+)-mitotano, apresentou maior afinidade pela coluna quiral. Valores de km superiores a 300 min-1 revelaram baixo efeito dos fenômenos de transferência de massa e consequentemente predomínio dos efeitos termodinâmicos (energia entálpica superior -10 kJ/mol para os enantiômeros). Experimentos a altas concentrações foram realizados com a finalidade de se determinar às isotermas pelo método da análise frontal e também os cromatogramas sob estas condições. Para a concentração da mistura até 16 g/L as isotermas mostraram um bom ajuste ao modelo de Langmuir. A partir da separação em batelada determinaram-se as regiões de separação dos enantiômeros para um sistema cromatográfico contínuo do tipo leito móvel simulado para diferentes concentrações de alimentação da mistura racêmica. Avaliaram-se as variáveis desempenho (consumo de solvente e produtividade) no sistema contínuo e compararam-se com as obtidas em separações em batelada. Melhores resultados foram obtidos para um sistema contínuo do tipo leito móvel simulado
Abstract: Mitotane (o, p'-dichlorodiphenyldichloroethane) is a drug used in the treatment of adrenocortical carcinoma. It is marketed in the racemic form, proportion 1:1 of their R and S enantiomers. The influence of the molecule quirality on its pharmacology effect was not studied yet. For this reason, this separation is important for comparative biological tests of collateral effects. This work was developed with intention to study the separation of this drug via liquid chromatography using columns packed with the chiral stationary phase, O,O?-bis[4-terc-butylbenzoyl] - N, N' - diallyl-L-tartardiamide. Different combinations of mobile phase was tested and better results were achieved with hexane/ethyl acetate in ratio 95/5 (v/v). Pulses experiments with diluted solutions of the inert and the enantiomers were accomplished at different flow rates and temperature. The system porosities, chromatographic parameters, equilibrium constants, axial dispersion and mass transference parameters were obtained. The results showed satisfactory separation, with number of plates overcoming 9000 and separation factors in the order of 1,13. The values of Henry coefficients were greater than one for both enantiomers, the most retained was R (+) -mitotane, and it presented greater affinity for the chiral column. The overall mass transfer coefficient achieved values higher than 300 min-1, demonstrating low mass transfer effect rates and consequently a prevalence of the thermodynamic effects (enthalpy energy greater than -10 kJ/mol for the enantiomers). Experiments in overload conditions were realized in order to determining the isotherms using the method of the frontal analysis as well the chromatograms under these conditions. For the concentration of the mixture smaller than 16 g/L the isotherms showed a good adjusted to the Langmuir model. The separation regions for a chromatographic continuous system like simulated moving bed were determined with different feed concentrations. This permits the comparison of the performance parameters using the continuous system and batch ones
Mestrado
Desenvolvimento de Processos Biotecnologicos
Mestre em Engenharia Química

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Asp, Vendela. "In Vitro Studies of Adrenocorticolytic DDT Metabolites, with Special Focus on 3-methylsulfonyl-DDE". Doctoral thesis, Uppsala universitet, Ekotoxikologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-122721.

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The DDT metabolite 3-methylsulfonyl-DDE (3-MeSO2-DDE) is bioactivated by cytochrome P450 11B1 (CYP11B1) in the adrenal cortex of mice and forms irreversibly bound protein adducts, reduces glucocorticoid secretion, and induces cell death selectively in cortisol-producing adrenocortical cells. 3-MeSO2-DDE has therefore been proposed as a lead compound for an improved adrenocortical carcinoma (ACC) therapy. The aims of this thesis were to (1) develop in vitro test systems based on murine and human adrenocortical cell lines and to (2) investigate the mechanisms behind 3-MeSO2-DDE toxicity in adrenocortical cells. The cytotoxic and endocrine-modulating effects of 3-MeSO2-DDE were compared to those of o,p′-DDD (mitotane), the current ACC therapy, and to those of several structurally analogous compounds in both murine and human cell lines. 3-MeSO2-DDE bioactivation and cytotoxicity proceeded in a similar manner in the murine adrenocortical Y-1 cell line as in mice in vivo. The effects were highly structure-specific. Moreover, 3-MeSO2-DDE formed irreversibly bound protein adducts and caused cell death also in the human H295R cell line, and was slightly more cytotoxic than o,p′-DDD. However, 3-MeSO2-DDE toxicity in human cells was not affected by the CYP11B1 inhibitor etomidate, suggesting that bioactivation in human cells is performed by additional/other enzyme(s) than CYP11B1. 3-MeSO2-DDE generated biphasic responses in cortisol and aldosterone secretion and in expression levels of the steroidogenic genes CYP11B1, CYP11B2, and StAR. Such hormesis-like responses were not seen for o,p′-DDD or the precursor DDT metabolite p,p′-DDE. In addition, the two o,p′-DDD enantiomers (R)-(+)-o,p′-DDD and (S)-(-)-o,p′-DDD exhibited slight differences in cytotoxic and endocrine-modulating activity in H295R cells. In conclusion, this thesis provides extended knowledge on the mechanisms of action of 3-MeSO2-DDE and points out important differences in effects between murine and human cells. Lead optimisation studies of 3-MeSO2-DDE using the herein presented in vitro test systems are ongoing.

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Livros sobre o assunto "MitoTALEN"

Ball, Steve, e Sajid Kalathil. Adrenocortical cancer. Editado por James W. F. Catto. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199659579.003.0094.

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Adrenocortical cancer (ACC) is rare and associated with poor prognosis. The incidence is estimated at 0.7–2 cases per one million. Overall survival rate at five years for ACC is 37–47%. While the pathogenesis of ACC is incompletely understood, inherited predisposition syndromes are common in childhood ACC. Clinical presentation can be with symptoms and signs of hormone excess (functional tumours), mass effects, or as an incidental radiological finding. A multidisciplinary approach combining radiology, biochemistry, and tissue-based pathology is needed to establish a diagnosis to guide a surgical approach aimed at complete resection of the tumour where possible. At present, recommended first-line therapies for advanced disease are mitotane monotherapy or etopiside, doxorubicin, and cisplatin plus mitotane. Metronomic capecitabine and gemcitabine have been used as alternatives. Adjuvant radiotherapy to the tumour bed should be considered for patients considered to be at high risk of recurrence.

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Hugo, Aurélien Brackers de. Evaluation du Risque Ecotoxicologique des résidus médicamenteux: Le cas du Mitotane aux Hospices Civils de Lyon. Omniscriptum, 2012.

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Capítulos de livros sobre o assunto "MitoTALEN"

Terzolo, Massimo, Arianna Ardito, Barbara Zaggia, Silvia De Francia e Fulvia Daffara. "Mitotane". In Adrenocortical Carcinoma, 369–81. New York, NY: Springer New York, 2009. http://dx.doi.org/10.1007/978-0-387-77236-3_22.

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De Francia, Silvia, Paola Perotti, Vittoria Basile, Antonina Germano e Massimo Terzolo. "Adrenal Cortical Carcinoma: Mitotane and Beyond". In Contemporary Endocrinology, 311–30. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-62470-9_13.

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Arimura, Shin-ichi. "MitoTALENs: A Method for Targeted Gene Disruption in Plant Mitochondrial Genomes". In Methods in Molecular Biology, 335–40. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1653-6_22.

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Kazama, Tomohiko, e Shin-ichi Arimura. "A Method for Precisely Identifying Modifications to Plant Mitochondrial Genomes by mitoTALENs". In Methods in Molecular Biology, 365–78. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-2922-2_25.

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"Mitotane". In Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions, 2362–63. Elsevier, 2006. http://dx.doi.org/10.1016/b0-44-451005-2/01044-5.

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Papich, Mark G. "Mitotane". In Saunders Handbook of Veterinary Drugs, 538–40. Elsevier, 2016. http://dx.doi.org/10.1016/b978-0-323-24485-5.00398-3.

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"Mitotane". In Meyler's Side Effects of Drugs, 1071. Elsevier, 2016. http://dx.doi.org/10.1016/b978-0-444-53717-1.01094-5.

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"Mitotane." In Drugs Handbook 2012–2013. Bloomsbury Academic, 2011. http://dx.doi.org/10.5040/9781350363595.art-1148.

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Furman, Brian L. "Mitotane". In xPharm: The Comprehensive Pharmacology Reference, 1–4. Elsevier, 2007. http://dx.doi.org/10.1016/b978-008055232-3.62198-1.

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Furman, B. L. "Mitotane ☆". In Reference Module in Biomedical Sciences. Elsevier, 2017. http://dx.doi.org/10.1016/b978-0-12-801238-3.98010-3.

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Trabalhos de conferências sobre o assunto "MitoTALEN"

Santana, Amanda S., Felipe R. Sampaio e Carlos Roque D. Correia. "Synthesis of New Mitotane Analogues". In 15th Brazilian Meeting on Organic Synthesis. São Paulo: Editora Edgard Blücher, 2013. http://dx.doi.org/10.5151/chempro-15bmos-bmos2013_2013914141646.

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Herry, H., A. Schmouchkovitch, P. Thuillier, V. Kerlan, G. Le Toux e S. Boisramé. "Lichen plan buccal induit par Mitotane : à propos d’un cas". In 64ème Congrès de la SFCO, editado por S. Boisramé, S. Cousty, J. C. Deschaumes, V. Descroix, L. Devoize, P. Lesclous, C. Mauprivez e T. Fortin. Les Ulis, France: EDP Sciences, 2016. http://dx.doi.org/10.1051/sfco/20166403024.

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Garg, Madhu B., Jennette A. Sakoff e Stephen P. Ackland. "Abstract 1671: A simple HPLC method to measure plasma mitotane and its two main metabolites in adrenocortical cancer patients". In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-1671.

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