Percorrer por autor "Marques, Fernanda"
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- Antitumoral and antimicrobial activities of block copolymer micelles containing gold bisdithiolate complexesPublication . Sousa, Andreia; Santos, Joana F.; Silva, Francisco; Sousa, Sílvia A.; Leitão, Jorge H.; Matos, António P.; Pinheiro, Teresa; Silva, Rafaela A. L.; Belo, Dulce; Almeida, Manuel; Marques, Fernanda; Fernandes, CéliaGold(III) bisdithiolate complexes have been reported as potential antimicrobial and antitumoral agents. The complex [Au(cdc)2]− (cdc=cyanodithioimido carbonate) displayed antimicrobial and outstanding antitumor activity against the ovarian cancer cells A2780 and A2780cisR, which are sensitive and resistant to cisplatin, respectively. However, poor water solubility may hamper its clinical use. Block copolymer micelles (BCMs) may solubilize hydrophobic drugs, improving their bioavailability and circulation time in blood. Aiming to provide water solubility, prolonged availability, and enhanced therapeutic indexes, BCMs loaded with [Au(cdc)2]− were synthesized and characterized. The BCM-[Au(cdc)2] micelles were prepared with a loading efficiency of 64.6% and a loading content of 35.3 mg [Au(cdc)2]−/gBCM. A hydrodynamic diameter of 77.31 ± 27.00 nm and a low polydispersity index of 0.18 indicated that the micelles were homogenous and good candidates for drug delivery. Cytotoxic activity studies against A2780/A2780cisR cells showed that BCM-[Au(cdc)2] maintained relevant cytotoxic activity comparable to the cytotoxicity observed for the same concentration of gold complexes. The Au uptake in A2780 cells, determined by PIXE, was ca. 17% higher for BCMs-[Au(cdc)2] compared to [Au(cdc)2]−. The BCMs-[Au(cdc)2] presented antimicrobial activity against S. aureus Newman and C. glabrata CBS138. These results evidenced the potential of BCM-[Au(cdc)2] for drug delivery and its promising anticancer and antimicrobial activities.
- Assessment of carrier-free metallacarboranes for targeted radiation therapies PBFT and BNCT : comparative cellular effects and dosimetry studies with [o-FESAN]− in breast cancer cellsPublication . Di Maria, Salvatore; Pinheiro, Teresa; Alves, Luís Cerqueira; Bitonto, Valeria; Protti, Nicoletta; Crich, Simonetta Geninatti; Nishimura, Kai; Nakamura, Hiroyuki; Matos, António P.; Pinto, Catarina I. G.; Mendes, Filipa; Teixidor, Francesc; Viñas, Clara; Marques, FernandaBackground: Ferrabis(dicarbollide) ([o-FESAN]−) in combination with proton–boron fusion therapy (PBFT) or boron neutron capture therapy (BNCT) are promising alternative radiation modalities for the treatment of breast cancer. The aim of this study was to explore the underlying effects of [o-FESAN]− radio enhancement on breast cancer cells in vitro and in vivo, and to perform comparative dosimetry calculations. Methods: The cellular effects on SKBR-3 and MDA-MB-231 breast cancer cells and MDA-MB-231 xenograft-bearing nude mice induced by carrier-free [o-FESAN]− after BNCT or PBFT were evaluated following recommended protocols. Monte Carlo (MC) dosimetry calculations were performed at the cellular scale for both radiation modalities. Results: Selective retention of [o-FESAN]− within the cytoplasm and nucleus of SKBR-3 and MDA-MB-231 breast cancer cells is demonstrated. Moreover, in vivo studies with MDA-MB-231 xenograft-bearing nude mice show appreciable accumulation of [o-FESAN]− in the tumor. Both radiation modalities induce loss of cellular viability and survival. Comparative dosimetry studies between proton and neutron irradiation agree with the viability data, showing a good correlation between absorbed dose vs. cellular effects. In the case of PBFT, cell structural changes are likely due to necrosis caused by the production of reactive oxygen species (ROS). To explain the radio enhancement effects in more detail, other mechanisms should be taken into consideration. Conclusions: Our results validate the effectiveness of both PBFT and BNCT therapeutic modalities, warranting further studies on carrier-free [o-FESAN]− as a candidate drug for potential clinical translation of radio enhancers in binary radiation therapies.
- Ausência do pretenso pai: qual a melhor alternativa numa investigação de paternidade?Publication . Dario, Ana Rita; Marques, Fernanda; Carvalho, Mónica; Amorim, António; Dourado, Catarina G.A maioria das perícias de investigação de parentesco biológico, realizadas pelo Serviço de Genética e Biologia Forense (SGBF), são requisitadas por ordem do Tribunal. A colheita de material biológico é realizada aos intervenientes que, habitualmente, consiste num trio constituído por pretenso pai, mãe e filho/a. No entanto, poderão existir alterações quanto ao número e tipo de intervenientes. Em situações em que, por algum motivo, o pretenso pai não está disponível, não são raras as vezes que o Tribunal questiona o SGBF, sobre quais os intervenientes, familiares do pretenso pai, poderão ser envolvidos na investigação, de modo a que os resultados estatísticos sejam mais robustos. Nestes casos, recorre-se frequentemente aos pretensos avós paternos, irmãos do pretenso pai ou filhos do pretenso pai. Assim, quanto maior o número de familiares diretos para o estudo genético, maior será a probabilidade de paternidade que pode ser obtida. O objetivo deste trabalho consiste na análise de uma perícia de investigação de parentesco biológico, com ausência de pretenso pai, mas com a presença de vários familiares deste, e como a utilização de diferentes combinações destes perfis genéticos nos cálculos estatísticos, conduzem ou não a diferenças significativas nos valores de Índice de Paternidade (IP) obtidos. As zaragatoas bucais, colhidas a cada interveniente, foram extraídas com Prep-n-Go Buffer (Applied Biosystems™) e com Chelex® 100 (Sigma-Aldrich®), amplificadas para STRs autossómicos com os kits GlobalFiler™ PCR Amplification Kit (Applied Biosystems™), PowerPlex® Fusion 6C System (Promega Corporation), e Investigator® HDplex Kit (Qiagen) e amplificadas para STRs do cromossoma Y com Yfiler™ Plus PCR Amplification Kit (Applied Biosystems™). A análise de fragmentos foi efetuada por eletroforese capilar no sequenciador automático 3500 Genetic Analyzer (Applied Biosystems™) e analisadas com o software GeneMapper® ID-X 1.4 (Applied Biosystems™). A análise estatística foi realizada utilizando o programa Familias 3. Foram obtidos resultados de IP bem distintos, consoante o tipo de relação biológica dos intervenientes, relativamente ao pretenso pai, utilizados nos cálculos estatísticos, realçando, uma vez mais, a preferência de determinados familiares em detrimento de outros.
- Dose rate effects on the selective radiosensitization of prostate cells by GRPR-targeted gold nanoparticlesPublication . Marques, Ana; Belchior, Ana; Silva, Francisco; Marques, Fernanda; Campello, Maria Paula Cabral; Pinheiro, Teresa; Santos, Pedro; Santos, Luis; Matos, António P. A.; Paulo, AntónioFor a while, gold nanoparticles (AuNPs) have been recognized as potential radiosensitizers in cancer radiation therapy, mainly due to their physical properties, making them appealing for medical applications. Nevertheless, the performance of AuNPs as radiosensitizers still raises important questions that need further investigation. Searching for selective prostate (PCa) radiosensitizing agents, we studied the radiosensitization capability of the target-specific AuNP-BBN in cancer versus non-cancerous prostate cells, including the evaluation of dose rate effects in comparison with non-targeted counterparts (AuNP-TDOTA). PCa cells were found to exhibit increased AuNP uptake when compared to non-tumoral ones, leading to a significant loss of cellular proliferation ability and complex DNA damage, evidenced by the occurrence of multiple micronucleus per binucleated cell, in the case of PC3 cells irradiated with 2 Gy of γ-rays, after incubation with AuNP-BBN. Remarkably, the treatment of the PC3 cells with AuNP-BBN led to a much stronger influence of the dose rate on the cellular survival upon γ-photon irradiation, as well as on their genomic instability. Overall, AuNP-BBN emerged in this study as a very promising nanotool for the efficient and selective radiosensitization of human prostate cancer PC3 cells, therefore deserving further preclinical evaluation in adequate animal models for prostate cancer radiotherapy.
- Gold(III) bisdithiolate complexes: molecular conductors that also exhibit anticancer and antimicrobial activitiesPublication . Marques, Fernanda; Sousa, Sílvia A.; Leitão, Jorge H.; Morais, Tânia S.; Le Gal, Yann; Lorcy, Dominique
- Hydrogel dressings loaded with anticancer/antimicrobial Ag(I) camphorimine complexes for treatment of malignant woundsPublication . Costa, Joana P.; Silva, Diana C.; Marques, Fernanda; Muazeia, Jeremias; Leitão, Jorge H.; Pinto, Carlos A.; Saraiva, Jorge A.; Serro, Ana P.; Carvalho, M. Fernanda N. N.The treatment of skin wounds caused by metastatic lesions is often difficult because not many medicines exist that simultaneously act on cancer cells and bacteria. Such difficulty delays and sometimes compromises the treatment of oncologic patients. To contribute to face that problem a set of silver camphorimine compounds with antibacterial properties were assessed for activity against cancer cells A375 and MeWo melanoma cells using the MTT assay. From them, the silver camphorimine complex 1 displayed the highest combined anticancer and antibacterial activities and therefore was incorporated in a HEMA-based hydrogel to be used in a wound dressing. The hydrogel disks loaded with complex 1 effectively reduced suspensions of E. coli, P. aeruginosa and B. contaminans from the initial 5 × 105 CFU/mL to 0 CFU/mL after 24 and 48 h of incubation. In the case of S. aureus, a reduction of more than 99 % was observed after 24 h. However, after 48 h of incubation, the hydrogel was ineffective towards S. aureus. Although presenting a non-porous structure, the hydrogel revealed to be hydrophilic and able to retain a significant water content, allowing to keep the wound moist. Additionally, it exhibited mechanical and mucoadhesive properties suitable for treatments involving repeated and frequent dressing changes. The hydrogels were loaded with complex 1 by soaking and then sterilized by high hydrostatic pressure (HHP). Biocompatibility studies demonstrated that the loaded dressings were non-irritant and hemocompatible. The sterilization procedure did not affect the integrity of the complex, nor the drug release, which occurred in a sustained way through a non-Fickian diffusion mechanism. The dressing released 618.5 mg/cm2/24 h, with nearly 90 % of the release occurring within the first 8 h. Considering the exudate production rates of chronic wounds and the MIC and MBC values for complex 1 it is expected that the dressings will be effective as antibacterial and anticancer agents. In vivo studies will be needed to confirm the clinical potential of the dressings. However, the produced dressings offer a promising approach for both infection control and cancer therapy in chronic wounds.
- Metal (Au, Pt, Pd, Ni) Bis(dithiolene) complexes as dual-action agents combating cancer and trypanosomatid infectionsPublication . Hachem, Hadi; Gal, Yann Le; Jeannin, Olivier; Lorcy, Dominique; Scalese, Gonzalo; Pérez-Díaz, Leticia; Gambino, Dinorah; Matos, António P.; Marques, FernandaCancer and infection diseases pose severe threats to public health worldwide stressing the need for more effective and efficient treatments. Thus, the search for broad-spectrum activity drugs seems justifiable and urgent. Herein, we investigate the anticancer and antitrypanosomatid (anti-Trypanosoma cruzi) activities of eight monoanionic metal bis(dithiolene) complexes, [Ph4P][M(R-thiazdt)2] with Mn+ = Au3+, Pt2+, Pd2+, Ni2+, containing N-alkyl-1,3-thiazoline-2-thione dithiolene ligands (R-thiazdt) with different alkyl groups (R = Et, tBu). Compared to auranofin (AF) and cisplatin (CP), two reference drugs in clinical use, all complexes showed high anticancer activities against A2780 ovarian cancer cells (IC50 values of 0.6–3.8 μM) some also being able to overcome CP resistance in A2780cisR cells. The selectivity index (SI), the IC50 values on normal cells (HDF) vs. A2780 cells, indicated good anticancer specificity (SI > 3) for most of the complexes but with clinical relevance for [Ph4P][Pd(tBu-thiazdt)2] (SI = 10). All complexes showed relevant antitrypanosomatid activities (IC50 values of 2.6–5.8 μM) some even exhibiting lower IC50 values than the reference drug nifurtimox (NFX). The mechanism of cell death seemed to be mediated mainly by the formation of reactive oxygen species (ROS), although to lesser extent for the gold complexes but superior to AF. Although ROS play a role in the main apoptotic pathways, cell death by apoptosis was not evident as shown by the caspase-3/7 assay and the morphological cell features studies by electron microscopy (SEM). Results obtained evidenced that [Ph4P][Pt(tBu-thiazdt)2] and [Ph4P][Pd(tBu-thiazdt)2] complexes might have potential as novel anticancer and antitrypanosomatid agents as alternatives to current therapeutics
- Modification of ZnO nanoparticles with silanes enables their application as anticancer agentsPublication . Marques, Fernanda; Tǎbǎcarub, Aurel; Bușilǎc, Mariana; Pinheiro, Teresa; Matos, António P. A.
- The Mössbauer effect using 57Fe-ferrabisdicarbollide ([o-57FESAN]−) : a glance into the potential of a low-dose approach for glioblastoma radiotherapyPublication . Buades, Ana B.; Pereira, Laura C. J.; Vieira, Bruno J. C.; Cerdeira, Ana C.; Waerenborgh, João C.; Pinheiro, Teresa; Matos, António P. A.; Pinto, Catarina G.; Guerreiro, Joana F.; Mendes, Filipa; Valic, Srecko; Teixidor, Francesc; Viñas, Clara; Marques, FernandaAlthough a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. To overcome this situation, more effective and selective treatments are necessary using anti-tumour agents that act in two or more ways and offer greater therapeutic benefits over single-mechanism entities. In this study, we report on treating cancer with Na[3,3′-57Fe(1,2-C2B9H11)2], which offers the possibility of dual action (radiation–drug combinations) to improve the clinical benefits and reduce healthy tissue toxicity. An approach to evaluating the potential of [o-57FESAN]− to treat glioblastoma using the Mössbauer effect is presented. As the therapeutic outcomes rely on the amount and distribution of [o-57FESAN]− inside the cells, several studies, using magnetization, Mössbauer spectroscopy and nuclear microscopy techniques, were performed to ascertain the uptake of [o-57FESAN]− in U87 glioblastoma cells. [o-57FESAN]− was found to be within the cells; 29% of its uptake was in the nuclear fraction, which is a particularly desirable target, because the nucleus is the cell's control centre where DNA and the transcription machinery reside. Irradiation studies with 2D and 3D cellular models of U87 cells showed that the growth inhibition effect observed was more pronounced when [o-57FESAN]− was used in combination with the Mössbauer effect in low total dose regimens, suggesting that this procedure either alone or as adjuvant may be useful for glioblastoma treatment.
- Oxigenoterapia de alto fluxo por traqueostomia no desmame ventilatório : scoping reviewPublication . Neiva, Sandrine; Maia, Diana; Pacheco, Artur; Marques, Fernanda; Ribeiro, Olga; Oliveira, João Pedrontrodução: A ventilação mecânica invasiva prolongada acarreta custos e tem complicaçõesassociadas. Um desmame ventilatório precoce com sucesso, assume cada vez mais importância,pretendendo-se neste estudo descrever as evidências acerca da utilização da Oxigenoterapia de AltoFluxo por Traqueostomia neste processo.Metodologia: Scoping Review segundo a metodologia do Joanna Briggs Institute®, com pesquisaefetuada nas bases de dados: CINHAL, PubMed e LILACS.Resultados: Incluíram-se quatro estudos: um estudo de caso e três estudos controlados randomizados.Relativamente aos protocolos utilizados na implementação da oxigenoterapia de alto fluxo portraqueostomia, eles variaram entre diferentes fluxos, tempo de utilização e combinação com outrosmodos ventilatórios. Os principais parâmetros monitorizados foram: frequência respiratória, FiO2,SpO2, PaO2, PaCO2 e a relação PaO2/FiO2.Discussão: A utilização de oxigenoterapia de alto fluxo por traqueostomia apresenta vantagens face àutilização de outros modos ventilatórios durante o processo de desmame ventilatório. Esta estratégiarepercute-se na melhoria dos parâmetros monitorizados e na diminuição do tempo de desmame.Conclusão: As principais contribuições da oxigenoterapia de alto fluxo por traqueostomia no desmameventilatório são: melhoria da oxigenação, diminuição do esforço respiratório, aumento do volumecorrente, diminuição do tempo de desmame e melhoria da eficácia da limpeza das vias aéreas.