A brief introduction to cancer biology and treatment is presented with a focus on current clinical advances in the delivery of chemotherapy and antiangiogenic therapies. Mathematical oncology is then surveyed with summaries of various models of tumor growth, tumor angiogenesis and other relevant biological entities such as angiogenic growth factors. Both strictly time-dependent ordinary differential equation (ODE)-based and spatial partial differential equation (PDE)-based models are considered. These biological models are first developed into an ODE model where various treatment options can be compared including different combinations of drugs and dosage schedules. This model gives way to a PDE model that includes the spatially heterogeneous blood vessel distribution found in tumors, as well as angiogenic growth factor imbalances. This model is similarly analyzed and implications are summarized. Finally, including the effects of interstitial fluid pressure into an angiogenic activity model is performed. This model displays the importance of factor convection on the angiogenic behaviour of tumours.

A brief introduction to cancer biology and treatment is presented with a focus on current clinical advances in the delivery of chemotherapy and antiangiogenic therapies. Mathematical oncology is then surveyed with summaries of various models of tumor growth, tumor angiogenesis and other relevant biological entities such as angiogenic growth factors. Both strictly time-dependent ordinary differential equation (ODE)-based and spatial partial differential equation (PDE)-based models are considered. These biological models are first developed into an ODE model where various treatment options can be compared including different combinations of drugs and dosage schedules. This model gives way to a PDE model that includes the spatially heterogeneous blood vessel distribution found in tumors, as well as angiogenic growth factor imbalances. This model is similarly analyzed and implications are summarized. Finally, including the effects of interstitial fluid pressure into an angiogenic activity model is performed. This model displays the importance of factor convection on the angiogenic behaviour of tumours.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2015-02-20T15:09:52Z No. of bitstreams: 2 Dissertação - Tatiana Vieira de Brito Marquez - 2010.pdf: 2722177 bytes, checksum: d3f571bcc9c3e44cf51b9d4539e6191d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Erika Demachki (erikademachki@gmail.com) on 2015-02-20T15:10:12Z (GMT) No. of bitstreams: 2 Dissertação - Tatiana Vieira de Brito Marquez - 2010.pdf: 2722177 bytes, checksum: d3f571bcc9c3e44cf51b9d4539e6191d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-02-20T15:10:12Z (GMT). No. of bitstreams: 2 Dissertação - Tatiana Vieira de Brito Marquez - 2010.pdf: 2722177 bytes, checksum: d3f571bcc9c3e44cf51b9d4539e6191d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2010-07-06 / OBJECTIVES: To compare the response of bevacizumab and the response of the laser photocoagulation with indirect binocular ophthalmoscope (IBO) in infants with retinopathy of prematurity (ROP) stages II or III. METHODS: Data collection was performed in the neonatal intensive care unit of the Hospital Materno Infantil, from May to November 2009. Preterm infants with ROP stages II or III, with or without the plus disease were included. They were divided into two groups: on group I, an intra-vitreous injection of bevacizumab was performed and on group II, laser photocoagulation with IBO was performed. RESULTS: In group I, from the 20 eyes that underwent the application of bevacizumab, there was total regression of ROP with one application in 14 eyes, being 4 eyes with complete regression with two doses of bevacizumab, and 2 eyes with total regression after two applications of bevacizumab and one application of laser. On group II, from the 20 eyes treated with laser photocoagulation with IBO, there was total regression of ROP with laser therapy in 14 eyes and there was total regression with two laser sessions in 6 eyes. CONCLUSION: Bevacizumab is effective if compared to laser photocoagulation in ROP stages II and III. / OBJETIVOS: Comparar a resposta terapêutica do bevacizumabe intravítreo com à resposta da fotocoagulação a laser com oftalmoscópio binocular indireto, em prematuros portadores de retinopatia da prematuridade estágios II ou III. MÉTODOS: A coleta de dados foi realizada na UTI neonatal do Hospital Materno Infantil, no período de maio a novembro de 2009. Foram incluídos os prematuros com retinopatia da prematuridade graus II ou III, com ou sem doença plus. Estes foram divididos em dois grupos: no grupo I foi realizada a injeção intra-vitrea de bevacizumabe, no grupo II foi realizada a fotocoagulação a laser com oftalmoscópio binocular indireto. RESULTADOS: No grupo I, dos 20 olhos incluídos, houve regressão total da retinopatia da prematuridade com uma aplicação de bevacizumabe em 14 olhos, regressão total com duas aplicações em 4 olhos e regressão total após duas aplicações de bevacizumabe e uma aplicação de laser em 2 olhos. No grupo II, dos 20 olhos tratados com fotocoagulação a laser com oftalmoscópio binocular indireto, houve regressão total da retinopatia da prematuridade com uma sessão em 14 olhos e houve regressão total com duas sessões em 6 olhos. CONCLUSÃO: O bevacizumabe é tão eficiente quanto a fotocoagulação a laser na retinopatia da prematuridade nos estágios II e III.

Mantle cell lymphoma (MCL) is a subtype of B-non-Hodgkin's lymphoma, characterized by often relapses. Despite an Ibrutinib (a Bruton's kinase inhibitor) implementation into salvage therapy, these patients often relapse with biologically highly aggressive disease and very poor prognosis. An increased activation of alternative metabolic pathways was described as one of ibrutinib-resistance mechanisms. Some of these pathways have also significant proangiogenic activity (e.g. PI3K-AKT-mTOR). In presented study, we established and standardized a real-time ultrasound and photoacoustic imaging of neovascularization and tissue oxygenation of subcutaneous MCL tumors in mice. Ultrasound and photoacoustic imaging is a fast, non-invasive method for angiogenesis evaluation in subcutaneous tumors with huge preclinical potential. Using MCL mice models, we also demonstrated the importance of CD31/PECAM-1 expression for engraftment, growth and spread of MCL cells in vivo. The level of CD31 expression in primary MCL cell (obtained directly from MCL patients) positively correlates with extent of extranodal involvement. CD31 facilitates survival and regulates extranodal spread of mantle cell lymphoma. We found that increased VEGFA expression causes not only increased microvessel density due to higher sprouting...