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A Novel µ-Fluidic Channel Assisted Encapsulation Technique for Layer-by-LayerPolymer Nano- and Microcarrier FabricationLi, Jingyu 15 September 2015 (has links)
No description available.
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Biodegradable paclitaxel-loaded plga microspheres for regional treatment of peritoneal cancersTsai, Max Chia-Shin January 2003 (has links)
No description available.
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Evaluation of combination cancer chemotherapy: theory and practiceZhao, Liang January 2003 (has links)
No description available.
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Optimization of cancer chemotherapy: local delivery of paclitaxel and pharmacokinetics of suraminHu, Xiao January 2004 (has links)
No description available.
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An approach to drug formulation and targeting liposomes and lipid nanoparticles for folate receptor targetingStevens, Phillip James 19 April 2005 (has links)
No description available.
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Progress toward the total synthesis of paclitaxel (taxol)Kreilein, Matthew M. 13 July 2005 (has links)
No description available.
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Impact des protéines de la famille Bcl-2 dans l'induction de l'apoptose par les agents anti-microtubules. / Impact of Bcl-2 proteins in induction of apoptosis mediated by microtubules targeting agentsSavry, Amandine 06 December 2012 (has links)
Les agents anti-microtubules (MTAs), comme les taxanes et les vinca-alcaloïdes, sont des anticancéreux largement utilisés en pratique clinique. Ils agissent d'une part en perturbant les fonctions du réseau microtubulaire, conduisant à un arrêt du cycle cellulaire. D'autre part, à côté de cet effet anti-prolifératif, les MTAs sont capables d'induire divers signaux responsables de l'exécution du programme apoptotique via la voie mitochondriale intrinsèque. La famille Bcl-2 joue un rôle primordial dans l'induction de l'apoptose par ces agents. Aussi, au cours de ce travail, nous nous sommes d'abord intéressés à l'origine de la diminution de Bcl-2 lors de l'apoptose médiée par la vinorelbine. Nous avons ainsi mis en évidence la régulation transcriptionnelle de bcl-2 grâce à l'identification d'un nouveau site de liaison de p53 sur le promoteur de bcl-2. Dans un second temps, nous avons évalué l'influence de la famille Bcl-2 dans la réponse aux MTAs. En effet, nous nous sommes focalisés sur la sensibilité paradoxale aux MTAs de certaines tumeurs surexprimant Bcl-2, in vitro et in vivo chez la souris nude. Nous avons montré l'implication de Bim dans cette augmentation de sensibilité, qui agit en perturbant le réseau mitochondrial. Enfin, nous avons investigué le mécanisme moléculaire liant la surexpression de Bcl-2 et celle de Bim. Nous avons montré que la surexpression de Bcl-2, en inhibant l'activité transcriptionnelle de p53, permettait une meilleure activité du facteur de transcription FoxO3a, principal acteur de la régulation génique de Bim. / Microtubule targeting agents (MTAs), such as taxanes and vinca-alkaloïds, are anticancer drugs widely used in clinical practice. Firstly, they are known to disturb functions of microtubular network, leading to cell cycle arrest. On the other hand, beside this anti-proliferative effect, MTAs are able to trigger signaling cascades leading to apoptosis execution, through intrinsic mitochondrial pathway. Bcl-2 family proteins play a crucial role in induction of MTAs-induced apoptosis. In this work, we first studied the origin of Bcl-2 downregulation in vinorelbine-mediated apoptosis. We thus highlighted a transcriptional mechanism through the identification of a novel p53 binding site in the bcl-2 promoter. Second, we evaluated the influence of Bcl-2 family in response to MTAs. Indeed, we focused on paradoxical sensitivity to MTAs of some tumors overexpressing Bcl-2, in vitro and in vivo in nude mouse. Bim was involved in this enhanced sensitivity, by disrupting the mitochondrial network. We then investigated the molecular mechanism linking Bcl-2 and Bim overexpressions. We showed that Bcl-2 overexpression, by inhibiting the transcriptional activity of p53, leads to an increase in activity of the transcription factor FoxO3a, the main actor in Bim transcriptional regulation. Our work underlines the importance of Bcl-2 family and especially Bim as potential biomarker in predicting MTA's efficacy.
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Uso de emulsão lipídica como veículo do paclitaxel na terapia sistêmica do carcinoma da mama / Use of a lipidic emulsion as vehicle of paclitaxel in systemic therapy of breast cancerPires, Luis Antonio 26 September 2006 (has links)
INTRODUÇÃO: Estudos mostraram que, após a injeção de LDE na corrente sangüínea de mulheres portadoras de câncer de mama, ela encontra-se mais concentrada em tecido neoplásico que no tecido normal. Recentemente, estudos pré-clínicos comprovaram que a associação LDE-oleato de paclitaxel é estável, menos tóxica e com mais atividade terapêutica quando comparada ao uso de paclitaxel comercial em animais. O presente estudo teve como objetivo verificar a estabilidade dessa associação na circulação, a sua capacidade em se concentrar no tecido neoplásico e determinar os parâmetros farmacocinéticos em relação ao paclitaxel isolado. MÉTODOS: Para determinar os parâmetros farmacocinéticos foram administrados, por via intravenosa, [3H]-oleato de paclitaxel associado a [14C]- oleato de colesterol-LDE em três pacientes e [3H]-paclitaxel comercial em duas pacientes 24 horas antes do procedimento cirúrgico. Todas as pacientes eram portadoras de neoplasia maligna da mama. Amostras de sangue foram colhidas durante 24 horas. A radioatividade foi medida por cintilação líquida e os parâmetros farmacocinéticos foram calculados usando um modelo multicompartimental. Fragmentos de tecido neoplásico e de tecido normal mamário foram coletados durante a cirurgia e submetidos à contagem radioativa. RESULTADOS: As taxas fracionais de remoção da LDE e do oleato de paclitaxel foram semelhantes (0,0296 ± 0,0264 e 0,0182 ± 0,0186, respectivamente, p = 0,5742). A captação tanto da LDE quanto do oleato de paclitaxel mostrou concentração 2,5 a 3 vezes maior no tecido tumoral do que no tecido mamário normal. O tempo de meia vida do oleato de paclitaxel foi maior do que o da formulação comercial (18,97 ± 7,7 horas e 7,34 ± 0,40 horas) e, a depuração plasmática, menor (1,51 ± 0,18 (L/h) e 7,95 ± 4,32 (L/h)). CONCLUSÃO: A maior parte do fármaco ficou retido na microemulsão até sua remoção da circulação e captação pelas células. O oleato de paclitaxel associado à LDE mostrou-se estável na circulação sangüínea e apresentou tempo de meia vida maior e a depuração plasmática menor do que a formulação comercial, além de se concentrar mais no tecido neoplásico da mama. Os resultados permitem sugerir que essa associação pode se constituir em uma estratégia útil no tratamento de mulheres portadoras de câncer da mama. / INTRODUCTION: Studies had shown that, after the injection of LDE in the circulation of women with breast cancer, it was more concentrate in neoplastic tissue that in the normal tissue. Recently, studies had proven that the LDE-paclitaxel oleate association is steady, less toxic and with more therapeutical activity when compared with the commercial paclitaxel in animals. The present study was designed to verify the stability of this association in the circulation, its capacity in concentrating in the neoplastic tissue and to determine the plasma kinetics of the association compared to that of paclitaxel isolated. METHODS: To determine the pharmacokinetic parameters, [3H]-paclitaxel oleate associated to LDE labeled with [14C]-cholesterol oleate was intravenously injected into three patients and [3H]-commercial paclitaxel into two patients 24 hours before the surgical procedure. All the patients had breast cancer. Blood samples were collected during 24 hours. Radioactivity was quantified in a scintillation solution and the pharmacokinetic parameters were calculated by compartmental analysis. Specimens of tumoral and normal breast were excised during the surgery and submitted to a radioactive counting. RESULTS: Fractional clearance rate of LDE and of the paclitaxel oleate were similar (0,0296 ± 0,0264 and 0,0182 ± 0,0186, respectively, p = 0,5742). The uptake of both [14C]-LDE and [3H]-paclitaxel oleate by breast malignant tissue was two and three fold greater than that of the normal breast tissue. The paclitaxel oleate plasma half-life (h) was greater than the commercial paclitaxel (T1/2 = 18,97 ± 7,7 and 7,34 ± 0,40) and the total plasma clearence (L/h) of paclitaxel oleate was lesser than the commercial (CL = 1,51 ± 0,18 and 7,95 ± 4,32). CONCLUSION: Most of the drug was restrained in the microemulsion until its removal from the circulation and captation by the cells. The paclitaxel oleate associated to LDE is stable in the bloodstream and has greater plasma half-life and lesser clearence than those for commercial paclitaxel. In addition, the association could be concentrated more in malignant breast tissue. The results allow to suggest that this association can consist in a useful strategy in the treatment of women with breast cancer.
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Avaliação preliminar do tratamento de pacientes portadoras de câncer de ovário avançado com nanopartícula lipídica associada ao quimioterápico paclitaxel / Preliminary evaluation of treatment of patients with advanced ovarian cancer with lipid nanoparticle associated with chemotherapy paclitaxelVital, Carolina Graziani 17 January 2017 (has links)
Introdução: O câncer de ovário é frequentemente diagnosticado em estágios avançados e é pouco responsivo aos tratamentos empregados atualmente. O tratamento de primeira linha consiste em esquemas incluindo cirurgia citorredutora seguido de quimioterapia adjuvante por derivados de platina e taxano. Os esquemas de segunda linha são baseados em gemcitabina e doxorrubicina lipossomal. Em seguida, a doença tende a progredir rapidamente e a quimioterapia não é indicada pela ausência de resposta e pela alta toxicidade desses medicamentos. Anteriormente, mostramos que nanopartículas lipídicas semelhantes à composição química da LDL, porém sem proteína, e associadas à agentes antineoplásicos são captadas por células neoplásicas. Objetivos: Testamos a hipótese se o paclitaxel associado à nanopartícula poderia beneficiar com segurança pacientes com câncer de ovário avançado e refratário ao tratamento, e portanto, não mais elegíveis para quimioterapia convencional. Métodos: Quatorze mulheres com câncer de ovário avançado de 61 ± 10 anos, com estadiamento clínico IV e TqNqM1 (FIGO e TNM Scale, respectivamente) que não eram responsivas à quimioterapia em terceira linha foram incluídas no estudo. O tratamento consistiu com o paclitaxel associado à nanopartícula na dose 175 mg/m2 de superfície corporal, a cada 3 semanas. As pacientes foram submetidas a exames clínicos antes de cada ciclo de quimioterapia. Determinações bioquímicas séricas e exames de imagem foram realizados para acompanhamento de novas lesões ou progressão da doença. Resultados: Foi realizado o total de 74 ciclos, e não foram observadas toxicidades laboratoriais e clínicas. Em quatro pacientes a doença permaneceu estável. Conclusões: A notável ausência de toxicidade, não registrada na literatura até hoje nos vários sistemas de veiculação descritos abre uma nova perspectiva de tratamento da doença. Evita-se o desconforto e os riscos da quimioterapia convencional, podem ser incluídos pacientes muito idosos ou com outras fragilidades que contraindiquem a quimioterapia e não há limite para a continuação do tratamento. / Introduction: Ovarian cancer is often diagnosed at advanced stages and is poorly responsive to standard treatment. First-line treatment consists in schemes including citorreductive surgery followed by adjuvant chemotherapy schemes with platinum and taxane derivatives. Second-line regimens are based in gemcitabine and liposomal doxorubicin. Thereafter, the disease progresses rapidly and chemotherapy is no longer indicated for lack of response rate together with high toxicity of antineoplastic agents. Previously, we showed that non-protein lipid nanoparticles resembling chemical structure of LDL, however without protein and associated with antineoplastic agents are uptaken by neoplastic cells. Aims: We tested the hypothesis whether paclitaxel associated to the nanoparticle could safely benefit patients with advanced ovarian cancer refractory to previous treatment, thus not eligible for further conventional chemotherapy. Methodology: Fourteen women with advanced ovarian cancer aged 61 ± 10 years were included, with clinical stage IV and TqNqM1 (FIGO and TNM Scale, respectively) that were unresponsive for third line chemotherapy treatments. Treatment consisted with paclitaxel associated to the nanoparticle at 175 mg/m2 body surface dose, every 3 weeks. Patients were submitted to clinical examinations before each chemotherapy cycle. Serum biochemistry determinations and imaging exams were performed to monitoring new lesions or disease progression. Results: Total of 74 cycles of chemotherapy was performed, clinical and laboratorial toxicities were not observed. Four patients stayed with stable disease. Conclusions: The notable absence of toxicity, not recorded in the oncology literature to date described in various drug delivery systems, opens a new perspective on the treatment of cancer. Avoiding the discomfort and risks of conventional chemotherapy, can be included very aged patients or with other weaknesses, that chemotherapy is contraindicated, and there is no limit for continued treatment.
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"Implante de stent revestido com paclitaxel em pacientes com infarto agudo do miocárdio em comparação com stent convencional: um estudo prospectivo, com avaliação clínica, angiográfica e ultra-sonográfica" / Paclitaxel-eluting stent implantation for acute myocardial infarction in comparison with conventional stenting : a clinical, angiographic, and IVUS prospective studyMartino, Fernando de 13 January 2006 (has links)
Fundamentos: Este estudo tem o objetivo de comparar os resultados clínicos e angiográficos de pacientes com infarto agudo do miocárdio(IAM) tratados com implante de stent revestido com paclitaxel (SRP) versus stent convencional. Métodos e população do estudo: Um grupo de 30 pacientes com infarto agudo do miocárdio foi tratados com stent revestido com paclitaxel (TaxusTM). Um grupo controle com 30 pacientes foi tratado com stent convencional (Express2 TM).Resultados: Aos 6,9±1,2 meses, não ocorreu morte, reinfarto ou trombose intra-stent. Entretanto, pacientes tratados com stent farmacológico tiveram um risco menor de reintervenção (3.3%% vs. 33.3%; p=0.006). A perda luminal tardia foi de 0.2±0.2 mm no grupo de SRP vs. 0.6±0.6 mm (p=0.03) no controle e a reestenose binária foi de 3.3% (RVP)vs. 33.3%(controle) (p=0.006). O percentual médio de obstrução neointimal em pacientes do grupo farmacológico foi de 4,7%±6,8%. Conclusões: O SRP se mostrou seguro e efetivo aos 7 meses em pacientes com IAM / This study aimed to compare the clinical and angiographic outcomes of patients with acute myocardial infarction (AMI) treated with paclitaxel eluting stent (PES) versus conventional stent implantation. Methods and Study Population: A group of 30 patients admitted with AMI was treated with PES (TaxusTM). A control group comprised 30 patients with a similar bare stent (Express IITM). Results: Baseline and procedural characteristics were similar between the PES and control groups. At 6.9±1.2 months, there were no deaths, re-AMI, or stent thrombosis. However, patients treated with PES had a lower risk of repeat revascularization (3.3%% vs. 33.3%; p=0.006). The angiographic late loss was 0.2±0.2 mm vs. 0.6±0.6 mm (p=0.03) and the binary restenosis rate was 3.3% vs. 33.3% (p=0.006) in the PES vs. controls respectively. The average percent neointimal obstruction in patients treated with PES was 4.7±6.8 %. Conclusions: PES appeared safe and effective at 7 months in patients AMI
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