Integrating FEUP's print service and information system at CICA

Estágio realizado no CICA-FEUP e orientado pelo Eng.º António Francelino Gomes VianaTese de mestrado integrado. Engenharia Informática e Computação. Faculdade de Engenharia. Universidade do Porto. 200

Interplay between glucose and palmitate uptake in breast carcinoma in vitro

One of the most studied tumor cells lines in vitro is the breast carcinoma MDA-MB-231 cell line. Several studies have proved its glycolytic profile, namely known as the Warburg effect. Glutamine oxidation is also important for its metabolism. Nevertheless, the use of fatty acids for obtaining energy in these cells is still rising. Palmitic acid is the most common saturated fatty acid, containing sixteen carbons in its structure. However, the use of palmitate for metabolic studies in MDA-MB-231 is not very extended due to its pro-apoptotic effect in this cell line after certain time exposure. Nonetheless, in this work we used palmitate as a metabolic fuel for just 30 minutes in order to see the almost immediate response of the cells to its presence, after a 30 minutes fast period. Our results show that MDA-MB-231 cells are not able of oxidizing palmitate nor producing lactate from it. Simultaneous presence of palmitate with glucose or with glutamine does not affect glucose nor glutamine uptake in these cells. However, we observed that even low concentrations of glucose increase palmitate uptake in MDA-MB-231 after a 30 minutes incubation. Treatment with 5 mM 2-deoxyglucose also for 30 minutes counters this rise, since 2-deoxyglucose diminishes palmitate uptake. Increasing glucose concentration to the same dosis of 2-deoxyglucose leads to a prevalence of the glucose effect on palmitate uptake. The exact role of glucose and glucose derivatives should be further studied in order to know more about palmitate metabolism in this cell line.Our experimental work is supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). This communication has the support of a travel grant "Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech"

Identification and characterization of new anti-angiogenic compounds from natural sources

The inhibition of angiogenesis has attracted broad attention in the field of pharmacological research, not only for cancer, but for other angiogenesis dependent diseases including ophthalmic, cutaneous and inflammatory diseases, as well as a number of rare diseases. Our research group has characterized multiple new natural bioactive compounds with multitargeted antiangiogenic effects by employing a well-established set of in vitro, in vivo and ex vivo preclinical models of angiogenesis. Most of them have been isolated from plants and terrestrial microorganisms, mainly due to their higher availability and because their therapeutic effects had been previously known in folk traditional medicines. In vitro primary screening includes cell differentiation and toxicity and proliferation assays. Secondary screening involves several experiments to evaluate effects on adhesion, migration, invasion, apoptosis or cell cycle analysis, among others. Additionally, we perform a further molecular characterization analyzing possible signaling pathways that are affected to elucidate their mechanism of action. The characterization is completed with the ex vivo aortic ring assay, and in vivo assays, as CAM and zebrafish assays, to ensure the anti-angiogenic ability. As a fruit of the mentioned screening, a number of compounds with remarkable anti-angiogenic activity have been identified and characterized.Our experimental work is supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain)]. This communicaction has the support of a travel grant "Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech"

Fasentin, a glucose uptake inhibitor, is also able to inhibit angiogenesis

Es comunicación a congreso en formato pósterThe role of glucose on endothelial cell (EC) metabolism and angiogenesis has been an emerging issue in the last few years. Some inhibitors of glucose metabolism, such as 2-deoxyglucose, have been shown to have anti-angiogenic effects. Fasentin is a poor-studied inhibitor of glucose uptake which modulates GLUT-1 and GLUT-4 transporters in cancer cells. We wanted to test its possible effect on EC glucose uptake, showing a light decrease in HMEC at 100 µM. Lower doses did not affect this characteristic of glucose metabolism. In line with this fact, fasentin at 100 µM totally inhibited tube formation on Matrigel in these cells. This anti-angiogenic effect is not likely to be helped by a pro-apoptotic effect of fasentin but, as proved with additional assays, it could be due to a decrease on the signaling for extracellular matrix degradation. More research would be necessary in order to elucidate its fine regulation on angiogenesis and metabolism.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. [Our experimental work is supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). This communicaction has the support of a travel grant "Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech"]

Selective use of postoperative neck radiotherapy in oral cavity and oropharynx cancer: a prospective clinical study

Background: In cervical postoperative radiotherapy, the target volume is usually the same as the extension of the previous dissection. We evaluated a protocol of selective irradiation according to the risk estimated for each dissected lymph node level. Methods: Eighty patients with oral/oropharyngeal cancer were included in this prospective clinical study between 2005 and 2008. Patients underwent surgery of the primary tumor and cervical dissection, with identification of positive nodal levels, followed by selective postoperative radiotherapy. Three types of selective nodal clinical target volume (CTV) were defined: CTV0, CTV1, and CTV2, with a subclinical disease risk of < 10%, 10-25%, and 25% and a prescribed radiation dose of < 35 Gy, 50 Gy, and 66-70 Gy, respectively. The localization of node failure was categorized as field, marginal, or outside the irradiated field. Results: A consistent pattern of cervical infiltration was observed in 97% of positive dissections. Lymph node failure occurred within a high-risk irradiated area (CTV1-CTV2) in 12 patients, marginal area (CTV1/CTVO) in 1 patient, and non-irradiated low-risk area (CTV0) in 2 patients. The volume of selective lymph node irradiation was below the standard radiation volume in 33 patients (mean of 118.6 cc per patient). This decrease in irradiated volume was associated with greater treatment compliance and reduced secondary toxicity. The three-year actuarial nodal control rate was 80%. Conclusion: This selective postoperative neck irradiation protocol was associated with a similar failure pattern to that observed after standard neck irradiation and achieved a significant reduction in target volume and secondary toxicity.This work was supported, in part, by Grants-in-Aid for Scientific Research from the Health Andalusian Authority PI-SAS-209/04

Synthesis and biological activity of a new class of antitumor cyclopeptides based on the solomonamides

Solomonamides A (1) and B (2) are novel natural products recently isolated from the marine sponge Theonella swinhoei [1]. Preliminary structural studies revealed an unprecedented cyclic peptide type structure. Interestingly, solomonamide A exhibits anti-inflammatory activity, showing potent reduction (60%) of inflammation at a very low concentration of 100 µg/kg in animal models. However, the scarcity of these compounds from their natural sources has been a drawback for further pharmacological assays. In fact, the anti-inflammatory activity of solomonamide B was not evaluated due to the limited amounts. This difficulty to access large amounts of these compounds makes quite difficult to gain insight into their biological profiles and mechanism of action and justifies the chemical synthesis of this new class of cyclic peptides. As a consequence, the solomonamides have been the subject of several synthetic efforts [2] notably by the Reddy group who has recently reported the first total synthesis of solomonamide B based on a intramolecular Heck reaction, which led to a revision of the initially proposed structure for 2 [3].Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Antitumor and antiangiogenic potential of solomonamide synthesis intermediates

Es comunicación (formato panel) a congreso internacionalIn this work we developed a new synthetic strategy towards the solomonamides. a novel class of cyclopeptides of marine origin. The described synthetic approach utilized an olefin metathesis reaction to form the [15]-membered ring contained in these natural products. During the synthetic process, a diverse set of analogues was generated and we evaluated their potential antitumor activity in vitro. For this purpose we performed in vitro proliferation assays, determining the IC50 values of the compounds in a panel of tumor cell lines. In addition, we evaluated the possible antiangiogenic effects of these solomonamide analogues by using in vitro endothelial cell differentiation assays. Our results showed that the potential antitumor and antiangiogenic activity of the studied analogues depended on their chemical structure, suggesting that the presence of specific functional groups could be responsible of their biological activity. Further studies are needed to understand the basis of the observed activities in endothelial and tumor cells.Our experimental work is supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). This communicaction has the support of a travel grant "Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Sistemas de clasificación de pacientes en centros de media y larga estancia: evolución y perspectivas de futuro

ResumenLa atención de media y larga estancia es un sector cada vez más importante de la prestación de cuidados sanitarios. La utilización de sistemas de clasificación de pacientes se contempla cada vez más como un elemento necesario tanto en la planificación como en la gestión de servicios en el sector de atención a enfermos crónicos y geriátricos.Aunque mucho menos conocidos, los sistemas de clasificación de pacientes han tenido en el sector de la atención de media y larga estancia un desarrollo mucho más rico y precoz que en el sector hospitalario. De este modo, puede verse la evolución desde clasificaciones basadas exclusivamente en la valoración de la capacidad funcional de los residentes, hacia clasificaciones que incluyen progresivamente variables de complejidad asistencial, hasta sistemas elaborados como la clasificación RUG-III.Los sistemas de clasificación de pacientes se utilizaron inicialmente como instrumentos para soportar los sistemas de financiación de los centros de media y larga estancia basándose en las características de paciente. Posteriormente, sus aplicaciones se han ido extendiendo hacia otros objetivos relacionados con la gestión de los centros, la evaluación de la calidad asistencial, la determinación de niveles de dotación de personal, el control del acceso a la atención y la formulación de políticas gubernamentales. En España, la única experiencia de utilización de un sistema de clasificación de pacientes es la del Programa Vida Als Anys en Cataluña, que desde 1990 utiliza una clasificación para la financiación de los centros acogidos al mismo.SummaryThe importance of long term care sector is increasingly growing. Actually, the use of patient classification systems is a useful tool for the planning and management of health services for chronic and geriatric patients.Despite being much less known, patient classification systems have had a richer and earlier development in the long term care sector than in the acute care sector. Thus, one could see the evolution from classifications based on the assessment of functional dependency to classifications progressively including variables corresponding to clinical complexity, and finally to complex systems such as RUG-III.Patient classification systems were first utilised as tools for the financing of long term centres, based on the patients' characteristics. Later, their applications have spread out to objectives related to the management of centres, assessment of quality of care, staff allocation level, control of access and national policies. In Spain, the only experience in the use of a patient classification system is the one used by the Catalan Health Care Administration which uses a classification for the financing of their centres