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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Prise en charge de patientes atteintes de cancer du sein et intégrées dans des essais cliniques au CRLCC de Nantes à propos du BCIRG 101 et du PACS 04 /

Le Bras, Claire Grimaud, Nicole January 2003 (has links) (PDF)
Thèse d'exercice : Pharmacie : Université de Nantes : 2003. / Bibliogr. f.104-112 [73 réf.].
2

The development of targeted TiO2 nanoparticles for the detection of trastuzumab responsive breast tumours by positron emission tomography

Cheyne, Richard William January 2011 (has links)
Screening of breast cancer patients for their tumour's prognostic marker status is necessary in determining the most suitable course of treatment. This is particularly important in the assessment of HER-2 expression status in identifying candidates who may respond to trastuzumab therapy. Current methods are limited in their effectiveness in accurately determining actual marker status.Discussed herein is an investigation into the development of a titanium dioxide nanoparticle system which may be applied as a medical imaging methodology through the use of positron emission tomography to gauge accurately a patient's HER-2 expression status in identifying candidates for trastuzumab therapy. The initial synthesis of organically coated ultra-small titanium dioxide nanoparticles is discussed in depth with respect to a range of coating molecules and further functionalisation. Additionally, methodology to elicit an exchange of these coat molecules is explored in detail resulting in the generation of TiO2 nanoparticles capable of forming long-term stable suspensions in water. An exploration of the synthesis of fluoride accepting groups for use in generating radiolabelled compounds is explored both successfully and unsuccessfully leading to the development of conditions suitable for radiolabelling aryltrifluoroborate compounds. Attempts to then combine these radionuclide accepting groups with biologically compatible TiO2 nanoparticles are discussed as an initial step toward the generation of a potential PET tracer. However, while this conjugation was achieved, a successful demonstration of the radiolabelling was not achieved requiring further focus on modulating the nanoparticle to easily allow its recovery from such reactions. Finally, an investigation into the effects of trastuzumab and cetuximab on FDG uptake by cells in vitro is discussed with respect to the potential of monitoring disease response to these drugs with conventional FDG-PET.
3

Consumo de trastuzumab en la Unidad de Mezclas Oncológicas del Hospital Nacional Edgardo Rebagliati Martins, periodo enero-diciembre 2009

Gallegos Castro, Jim William January 2011 (has links)
La Unidad de Mezclas Oncológicas (UMO), parte del Departamento de Farmacia del Hospital Nacional Edgardo Rebagliati Martins, genera indicadores de gestión; los cuales nos permiten cuantificar ciertas actividades que generan ahorro para el hospital a través de las actividades de preparación y reconstitución de medicamentos oncológicos; uno de ellos, trastuzumab, anticuerpo monoclonal utilizado para el tratamiento de Cáncer de Mama metastásico que sobreexpresa el gen HER2. Se estudio su consumo durante el periodo 2009, mediante un análisis descriptivo-retrospectivo de las hojas de trabajo de la UMO, la utilización del Sistema de Gestión Hospitalaria (SGH) y análisis de recetas prescritas y dispensadas. Los objetivos de este estudio son identificar los esquemas de tratamiento donde se utiliza trastuzumab, identificar y cuantificar el número de pacientes por esquema terapéutico, analizar el diagnostico, dosis y costo por esquema terapéutico, investigar el número de veces y frecuencia con que cada paciente recibe la terapia e identificar y cuantificar las devoluciones generadas por el consumo de trastuzumab en la UMO. Los resultados obtenidos muestran que hay diez esquemas terapéuticos que incluyen trastuzumab los cuales solo se aplican en el servicio de consulta externa de Oncología médica, el mayor grupo de pacientes ha recibido trastuzumab entre uno y seis meses, el mayor número de pacientes recibe trastuzumab como monoterapia y la mayor cantidad de pacientes oscila entre los 41 y 50 años, dentro de los esquemas de quimioterapia la mayor dosis promedio se recibe en el esquema de trastuzumab mas Gemcitabina (640 mg de trastuzumab), el costo que representan los esquemas de quimioterapia es de S/. 72 798,21; el esquema de quimioterapia que representa más gasto en nuevos soles para el HNERM es trastuzumab mas ixabepilona con un costo promedio en seis ciclos de S/. 68 684,52. De la comparación entre los anticuerpos monoclonales (rituximab, bevacizumab, cetuximab y trastuzumab) utilizados en la UMO para el servicio de Oncología médica, bevacizumanb es el más dispensado con 663 viales pero, trastuzumab es el más costoso con un gasto total de S/.3 798 719,89. La UMO atendió en total 542 prescripciones y realizó 521 preparaciones de trastuzumab, las cuales generaron un gasto de S/. 3 798 426 y las devoluciones ascendieron a S/. 704 442, lo cual genero un ahorro del 18,55%. -- Palabras claves: Trastuzumab, Unidad de Mezclas Oncológicas (UMO), Oncología médica, esquema de quimioterapia, anticuerpo monoclonal. / --- Mixtures Oncologic Unit (UMO), part of Pharmacy´s Department of Hospital Nacional Edgardo Rebagliati Martins, generate management indicators, which allow us to quantify some activities that generate savings for the hospital through generating activities of preparation and reconstitution Oncologic Drugs; one of them, trastuzumab, a monoclonal antibody used to treat metastatic breast cancer overexpressing the HER2 gene, studied its consumption during the period 2009 through retrospective descriptive analysis of the worksheets in the UMO and use of Hospital Management System (SGH) to analysis of written and dispensed prescriptions. The objectives of this study are identify treatment regimens in which trastuzumab is used to identify and quantify the number of patients per treatment regimen, discuss the diagnosis, cost per dose and therapeutic regimen, investigate the number of times each patient and often receiving therapy and to identify and quantify the returns generated by the use of trastuzumab in the UMO. The results show that there are ten regimens that include trastuzumab which only apply in Medical Oncologic Service outpatients, the largest group of patients received trastuzumab between one and six months, more patients receiving trastuzumab monotherapy and the largest number of patients ranges between 41 and 50 years, within the schemes of chemotherapy greater average dose received in the scheme of trastuzumab plus gemcitabine (640 mg of trastuzumab), cost accounting schemes chemotherapy is S /. 72 798.21, the chemotherapy scheme which accounts for more spending on new soles for more ixabepilone HNERM is trastuzumab with an average cost of six cycles of S/. 68 684,52. Comparing monoclonal antibodies (rituximab, bevacizumab, cetuximab and trastuzumab) used in UMO for Medical Oncology Service, bevacizumanb is the most dispensed with 663, but trastuzumab is the most expensive with a total of S/.3 798 719,89. UMO attended in total 542 prescriptions and 521 preparations with trastuzumab, which generated a cost of S /. 3 798 426 and returns amounted to S /. 704 442, which generated a savings of 18.55%. -- Keywords: Trastuzumab, Mixtures Oncologic Unit (UMO), medical oncology, chemotherapy regimen, monoclonal antibody.
4

Investigating a role of HER3 in anti-HER2 target therapy in breast cancer

Hashimoto, Kenji January 2014 (has links)
Background HER2-positive breast cancer is a poor prognostic subgroup, even if treated with anti-HER2 directed therapy. Trastuzumab is an important HER2-targeting antibody but only limited patients respond to this drug, and acquired resistance is a common problem. HER3 has been shown to be a key candidate in mediating resistance to trastuzumab and other ErbB inhibitors. The aims of the project are to investigate the resistance mechanisms and the relevant biomarkers in relation to trastuzumab treatment and resistance in HER2-positive breast cancer, in particular, HER3 subcellular localisation and HER3 phosphorylation. Methods Effects of trastuzumab on HER3 subcellular localisation and HER3 phosphorylation in relation to MET receptor were studied using western blots, nuclear fractionation, confocal microscopy, and immunoprecipitation in a panel of HER2-positive cell lines, including SKBr3 and BT474 breast cancer cells in which trastuzumab resistance was induced by long-term drug exposure. Effects of drug and knockdown experiments were tested by cell viability and proliferation assays. HER3 and MET expression was assessed by immunohistochemistry in xenograft tumours and human tissue samples, and clinical impact was assessed in different cohorts of HER2-positive breast cancer patients. Results Acquired trastuzumab resistant SKBr3 cells showed an increase of nuclear HER3<sub>100kD</sub>, which was derived from C-terminus of HER3. Nuclear HER3<sub>100kD</sub> could be due to the proteolytic cleavage of HER3 since it was reduced by ADAM17 or gamma-secretase inhibitor. In a panel of HER2-positive cell lines and xenograft samples, nuclear HER3 was observed only in the resistant cells. In addition, nuclear HER3 was associated with poor progression-free and overall survivals in HER2-positive breast cancer patients. It was also found that HER3 phosphorylation was maintained in acquired trastuzumab resistant cells, which was contributed by the ligand independent interaction of MET and HER3. Higher MET expression was associated with better overall survival in HER2-positive, breast cancer patients who were not treated with trastuzumab. Conclusions Nuclear HER3 was found in trastuzumab resistant cells and appeared to result from HER3 proteolytic cleavage mediated by ADAM17 and gamma-secretase. Further studies are required to investigate its mechanism and to identify the HER3 cleavage sites. MET was a key factor in maintaining HER3 phosphorylation during trastuzumab resistance. Lastly, nuclear HER3 and MET could be two potential biomarkers in HER2-positive breast cancer.
5

An analysis of trastuzumab as breast cancer treatment under Hong Kong medical system with a review on its clinical and cost effectiveness

Soong, Sung, Inda., 宋崧. January 2010 (has links)
published_or_final_version / Public Health / Master / Master of Public Health
6

Characterization and prevention of chemotherapy induced cardiac dysfunction

Zeglinski, Matthew 24 July 2012 (has links)
Background: Anthracyclines, in particular Doxorubicin (DOX), are highly effective chemotherapeutic agents in the breast cancer setting, which are limited by their cardiotoxic side effects. Recently, the introduction of Trastuzumab (TRZ), a novel monoclonal antibody against the HER2 receptor, in the breast cancer setting compounds the issue of DOX mediated cardiac dysfunction. Amongst the potential mechanisms for the deleterious effects of this drug-induced cardiomyopathy, the relationship between nitric oxide synthase 3 (NOS3) and oxidative stress has gained recent attention. Objective: To determine the role of NOS3 in a clinically relevant female murine model of DOX+TRZ induced heart failure. Methods: A total of 120 C57Bl/6 female mice [60 wild type (WT) and 60 NOS3 knockout (NOS3-/-)] were treated with either 0.9% saline, DOX (20 mg/kg), TRZ (10 mg/kg), or DOX+TRZ. Serial echocardiography was performed daily for a total of 10 days, after which the mice were euthanized for histological and biochemical analyses. Results: As compared to WT, NOS3-/- mice demonstrated increased cardiotoxicity following treatment with DOX. This effect was potentiated with DOX+TRZ combination therapy. In WT female mice receiving DOX+TRZ, left ventricular ejection fraction (LVEF) decreased from 75±3% at baseline to 46±2% at day 10 (p<0.05). In the NOS3-/- group, LVEF decreased from 72±3% at baseline to 35±2% at day 10 (p<0.05). LVEF was significantly lower in NOS3-/- mice than WT at day 10 in those receiving DOX+TRZ (p<0.05). As compared to WT, NOS3-/- mice also demonstrated increased mortality following treatment with DOX+TRZ, corroborating the echocardiographic findings. Histological analysis using light and electron microscopy demonstrated increased loss of cell integrity including myofibrillar degradation, cytoplasmic vacuolization, and enlargement of the smooth endoplasmic reticulum in both the WT and NOS3-/- mice treated with DOX+TRZ. There was no significant difference, however, in the degree of cardiac remodeling between the WT and NOS3-/- groups. There was an increasing trend in the degree of cardiac apoptosis in both WT and NOS3-/- mice treated with DOX+TRZ therapy. Conclusion: Congenital absence of NOS3 potentiates the cardiotoxic effects of DOX+TRZ in an acute female murine model of chemotherapy-induced cardiomyopathy.
7

Characterization and prevention of chemotherapy induced cardiac dysfunction

Zeglinski, Matthew 24 July 2012 (has links)
Background: Anthracyclines, in particular Doxorubicin (DOX), are highly effective chemotherapeutic agents in the breast cancer setting, which are limited by their cardiotoxic side effects. Recently, the introduction of Trastuzumab (TRZ), a novel monoclonal antibody against the HER2 receptor, in the breast cancer setting compounds the issue of DOX mediated cardiac dysfunction. Amongst the potential mechanisms for the deleterious effects of this drug-induced cardiomyopathy, the relationship between nitric oxide synthase 3 (NOS3) and oxidative stress has gained recent attention. Objective: To determine the role of NOS3 in a clinically relevant female murine model of DOX+TRZ induced heart failure. Methods: A total of 120 C57Bl/6 female mice [60 wild type (WT) and 60 NOS3 knockout (NOS3-/-)] were treated with either 0.9% saline, DOX (20 mg/kg), TRZ (10 mg/kg), or DOX+TRZ. Serial echocardiography was performed daily for a total of 10 days, after which the mice were euthanized for histological and biochemical analyses. Results: As compared to WT, NOS3-/- mice demonstrated increased cardiotoxicity following treatment with DOX. This effect was potentiated with DOX+TRZ combination therapy. In WT female mice receiving DOX+TRZ, left ventricular ejection fraction (LVEF) decreased from 75±3% at baseline to 46±2% at day 10 (p<0.05). In the NOS3-/- group, LVEF decreased from 72±3% at baseline to 35±2% at day 10 (p<0.05). LVEF was significantly lower in NOS3-/- mice than WT at day 10 in those receiving DOX+TRZ (p<0.05). As compared to WT, NOS3-/- mice also demonstrated increased mortality following treatment with DOX+TRZ, corroborating the echocardiographic findings. Histological analysis using light and electron microscopy demonstrated increased loss of cell integrity including myofibrillar degradation, cytoplasmic vacuolization, and enlargement of the smooth endoplasmic reticulum in both the WT and NOS3-/- mice treated with DOX+TRZ. There was no significant difference, however, in the degree of cardiac remodeling between the WT and NOS3-/- groups. There was an increasing trend in the degree of cardiac apoptosis in both WT and NOS3-/- mice treated with DOX+TRZ therapy. Conclusion: Congenital absence of NOS3 potentiates the cardiotoxic effects of DOX+TRZ in an acute female murine model of chemotherapy-induced cardiomyopathy.
8

Durable and Complete Response to Herceptin Monotherapy in Patients with Metastatic Gastroesophageal Cancer

Swofford, Brenen P., Dragovich, Tomislav 11 December 2017 (has links)
Gastroesophageal cancer is the sixth leading cause of cancer-related death worldwide. The 2 most common histologies are squamous cell carcinoma and adenocarcinoma, which has seen an increase in incidence correlating with an increase in obesity in developed countries. Gastroesophageal adenocarcinoma has a preponderance to metastasize early, making it a highly lethal cancer with a low 5-year survival rate of similar to 15-25%. Therefore, for the majority of patients, treatment focuses on palliation and prolongation of survival. Combination chemotherapy regimens, mostly platinum-based, have only modestly prolonged survival in patients with stage IV disease. Recently, it was discovered that the activation of the HER2 receptor plays an important role in a minority of adenocarcinomas of the distal esophagus and stomach. This introduced the treatment option of trastuzumab (Herceptin), a monoclonal antibody directed at the HER2 receptor, which has demonstrated improvement in overall and progression-free survival as noted in the ToGA trial. Currently, the role of Herceptin therapy beyond first-line therapy and outside of combination regimens is not well established. In this case report we review 2 cases of patients with gastroesophageal cancer, with HER2 overexpression, who achieved a robust response to trastuzumab in combination with chemotherapy and were able to maintain a durable response with maintenance trastuzumab monotherapy. (c) 2017 The Author(s) Published by S. Karger AG, Basel.
9

Trastuzumab som adjuvant behandling avbröstcancerpatienter med HER2-positivitet : Hur effektivt är det?

Stigsohn, Lovisa January 2011 (has links)
Breast cancer is the most common tumor disease among women in Sweden. About 7000persons, having a median age of 65, are diagnosed each year with this disease. Withmammography screening, breast cancer can be detected in an early stage which improves theoverall survival (OS). 20-30 % of the breast cancer tumors are overexpressing humanepidermal growth factor receptor 2 (HER2), which is a protein that stimulates cell proliferation.Trastuzumab (Herceptin®) is a humanised monoclonal antibody that targets the HER2-proteinand prevent the signals for cell proliferation.Trastuzumab has earlier been used for treatment of metastatic breast cancer. In the year of 2007trastuzumab was approved for adjuvant treatment of patients who has been medicated withsurgery and/or radiation.The aim of this study was to investigate the effects of adjuvant treatment with trastuzumab inHER2-positive breast cancer patients. The method was a literature study based on scientificarticles identified from the database PubMed.The articles that were choosen were two meta-analysis and three cohort studies. The benefitsand effects of trastuzumab administration on patients with HER2-positive breast cancer weredescribed in these articles. Primary endpoint was disease-free survival (DFS). All articlesshowed that the DFS increased in breast cancer patients treated with adjuvant trastuzumab but alonger follow-up of four years, showed a reduction of both DFS and OS.The conclusion of this study was that trastuzumab as adjuvant treatment is favorable and shouldbe considered as treatment of breast cancer with HER2 overexpression that has been analyzedby immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
10

Evaluation of cardiac toxicities in breast cancer patients treated with adjuvant chemotherapy and/or anti-her2 targeted agents: Late cardiac side-effects

De Azambuja, Evandro 15 December 2015 (has links)
L’hypothèse prédominante de cette thèse est que les traitements utilisés pour le cancer du sein de stade précoce (chimiothérapie avec des anthracyclines et/ou avec l’anticorps monoclonal trastuzumab) peuvent amener à des toxicités cardiaques à long terme, et qu’une évaluation de ce risque cardiaque ainsi qu’un suivi à long terme sont importants. Pour évaluer la toxicité cardiaque secondaire à ces deux agents chez les patientes avec un cancer du sein de stade précoce, nous avons réalisé deux séries d’études cliniques, la première pour évaluer la toxicité cardiaque à long terme induite par les anthracyclines, et la deuxième pour explorer la toxicité cardiaque induite par le trastuzumab. 1) Le premier chapitre de cette thèse explore la toxicité cardiaque à long terme induite par la chimiothérapie administrée aux patientes avec cancer du sein de stade précoce et ganglions positifs. La population de notre étude a été recrutée au sein de la population d’une étude de phase III randomisée menée entre 1988 et 1996 en Belgique et comparant trois schémas de traitement de chimiothérapie adjuvante, soit deux différents protocoles de chimiothérapies à base d’anthracyclines (basse dose ou haute dose d’epirubicine) ainsi qu’un schéma de chimiothérapie sans anthracyclines (CMF classique). Nous avons identifié 82 patientes (30%) traitées avec chimiothérapie adjuvante dans cette étude qui n’avaient pas de signe de récidive en 2010 (survivantes à long terme). Une évaluation cardiaque approfondie de ces patientes a été effectuée, incluant une échographie cardiaque, une résonance magnétique nucléaire, des marqueurs cardiaques sériques (pro-BNP et troponine), ainsi qu’un test de marche de 6 minutes. Cette étude nous a permis de démontrer que la toxicité cardiaque à long terme liée aux anthracyclines reste faible, et que la résonance magnétique est potentiellement plus précise que l’échographie cardiaque pour mesurer la fonction du ventricule gauche. Ceci devra cependant être confirmé dans d’autres études. Au cours de notre démarche, nous avons été confrontés à la difficulté de motiver les patientes plusieurs années après le traitement pour étudier les potentiels effets à long terme de ce dernier. 2) Le deuxième chapitre de cette thèse explore la toxicité cardiaque induite par l’anticorps monoclonal trastuzumab (anti-HER2). En un premier temps, nous avons examiné la toxicité cardiaque immédiate et à long terme au sein de la population de l’étude HERA, un large essai clinique randomisé de phase III du Breast International Group évaluant le bénéfice du trastuzumab en traitement adjuvant du cancer du sein HER2-positif. Après un suivi moyen de 8 ans des 5,102 participantes de l’étude, nous avons pu démontrer que la toxicité cardiaque demeure faible à long terme, avec très peu de nouveaux évènements cardiaques diagnostiqués dans la phase de suivi. Nous avons aussi pu démontrer que la toxicité cardiaque du trastuzumab apparait surtout pendant la phase de traitement, et qu’une fois le trastuzumab arrêté, la majorité des patientes récupèrent de l’épisode de toxicité cardiaque avec normalisation de la fraction d’éjection ventriculaire gauche. En un deuxième temps, en effectuant une analyse combinée de la toxicité cardiaque dans trois essais cliniques randomisés, nous avons démontré que l’usage concomitant du trastuzumab avec une chimiothérapie néo-adjuvante à base d’anthracyclines augmente le risque d’une toxicité cardiaque chez les patientes ayant un cancer du sein de stade précoce. Conséquemment, ces schémas de traitements ne sont pas recommandés de routine.En conclusion, une bonne évaluation cardiologique et oncologique doit avoir lieu avant de démarrer une chimiothérapie à base d’anthracyclines chez les patientes ayant un cancer du sein de stade précoce. Actuellement, la recommandation est d’évaluer les facteurs de risque cardiaque avant le traitement, et de suivre la fraction d’éjection du ventricule gauche avant, pendant et environs 6 mois après la fin du traitement. L’usage de marqueurs cardiaques et/ou de tests d’imagerie modernes pour un diagnostic de toxicité cardiaque tardive reste un domaine d’investigation intéressant. Pour les patientes avec un cancer du sein HER2-positif de stade précoce, le risque de toxicité cardiaque induite par le trastuzumab demeure faible. Cependant, les facteurs de risque doivent être évalués pour chaque patiente avant le traitement. L‘usage concomitant de trastuzumab et anthracyclines n’est pas recommandé vu le risque augmenté de toxicité cardiaque. En cas de facteurs de risque cardiaque, un dialogue étroit entre l’oncologue et le cardiologue est recommandé avant de débuter un traitement adjuvant. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

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