Urothelial bladder cancer progression: lessons learned from the bench

Urothelial bladder carcinoma (UBC) is an intricate malignancy with a variable natural history and clinical behavior. Despite developments in diagnosis/prognosis refinement and treatment modalities, the recurrence rate is high, and progression from non-muscle to muscle invasive UBC commonly leads to metastasis. Moreover, patients with muscle-invasive or extra-vesical disease often fail the standard chemotherapy treatment, and overall survival rates are poor. Thus, UBC remains a challenge in the oncology field, representing an ideal candidate for research on biomarkers that could identify patients at increased risk of recurrence, progression, and chemo-refractoriness. However, progress toward personalized medicine has been hampered by the unique genetic complexity of UBC. Recent genome-wide expression and sequencing studies have brought new insights into its molecular features, pathogenesis and clinical diversity, revealing a landscape where classical pathology is intersected by the novel and heterogeneous molecular groups. Hence, it seems plausible to postulate that only an integrated signature of prognostic/predictive biomarkers inherent in different cancer hallmarks will reach clinical validation. In this review, we have summarized ours and others' research into novel putative biomarkers of progression and chemoresistance that encompass several hallmarks of cancer: tumor neovascularization, invasion and metastasis, and energy metabolism reprogramming of the tumor microenvironment.

Molecular regulation of flowering induction in Quercus suber

Dissertação de mestrado em Plant Molecular Biology, Biotechnology and Bioentrepeneurship

The influence of kaolin application on key metabolic pathways associated with grape berry quality: a molecular and biochemical analysis

Dissertação de mestrado em Biologia Molecular, Biotecnologia e Bioempreendedorismo em Plantas

Prevalência e susceptibilidade de isolados clínicos de Pseudomonas aeruginosa numa unidade hospitalar de Portugal

Dissertação de mestrado em Bioquímica Aplicada (área de especialização em Biomedicina)

Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-Aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors

The synthesis and biological evaluation of novel 1-aryl-3-[2-, 3- or 4-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 3, 4 and 5 as VEGFR-2 tyrosine kinase inhibitors, are reported. The 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 4a-4h, with the arylurea in the meta position to the thioether, showed the lowest IC50 values in enzymatic assays (10-206 nM), the most potent compounds 4d-4h (IC50 10-28 nM) bearing hydrophobic groups (Me, F, CF3 and Cl) in the terminal phenyl ring. A convincing rationalization was achieved for the highest potent compounds 4 as type II VEGFR-2 inhibitors, based on the simultaneous presence of: (1) the thioether linker and (2) the arylurea moiety in the meta position. For compounds 4, significant inhibition of Human Umbilical Vein Endothelial Cells (HUVECs) proliferation (BrdU assay), migration (wound-healing assay) and tube formation were observed at low concentrations. These compounds have also shown to increase apoptosis using the TUNEL assay. Immunostaining for total and phosphorylated (active) VEGFR-2 was performed by Western blotting. The phosphorylation of the receptor was significantly inhibited at 1.0 and 2.5 microM for the most promising compounds. Altogether, these findings point to an antiangiogenic effect in HUVECs.

Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective

This review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85 % of all incident CC and 50 % of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country.

Study of grapevine solute transporters involved in berry quality. A biochemical and molecular approach

Tese de Doutoramento em Biologia de Plantas

Looking for mechanisms regulating lung growth in CDH: rat and human studies

Tese de Doutoramento em Ciências da Saúde

A patogênese genética e molecular da síndrome de Angelman

Objetivo: Fornecer uma revisão atualizada em língua portuguesa sobre a síndrome de Angelman, com ênfase nos mecanismos genéticos e moleculares dessa patologia, uma causa de deficiência mental severa que em alguns casos pode apresentar recorrência familiar. Método: Foi feita uma revisão bibliográfica utilizando a base de dados do PubMed, tendo como critérios de busca o termo "Angelman syndrome" isoladamente e combinado com "UBE3A", "clinical", "genetics" e "molecular" no título dos artigos. Dentre esses, foram selecionados artigos de revisão e artigos originais sobre a fisiopatologia da síndrome, com ênfase nos últimos dez anos. Resultados: Utilizando-se "Angelman syndrome" na busca, apareceram cerca de 1.100 artigos, incluindo 240 de revisão. Nos últimos dez anos são mais de 600 artigos, aproximadamente 120 de revisão, 50% dos quais publicados nos últimos cinco anos. Na base de dados SciELO, são apenas nove artigos sobre a síndrome, dos quais três em português e nenhum artigo atual de revisão. Conclusão: Após ter sido uma das principais causas que atraíram atenção ao estudo e ao entendimento dos mecanismos do imprinting genômico, a síndrome de Angelman está agora se revelando como uma patologia das sinapses. Apesar de o entendimento da fisiopatologia molecular da síndrome de Angelman ainda estar longe de ser compreendida, seu estudo está fornecendo uma visão extraordinária sobre os mecanismos que regem a plasticidade sináptica, novamente atraindo a atenção de pesquisadores que trabalham na fronteira do conhecimento.

Molecular mass distribution of materials solubilized by xylanase treatment of Douglas-Fir kraft pulp

Irgazyme, a commercial xylanase preparation from Trichoderma longibrachiatum, and xylanase D a purified enzyme from Trichoderma harzianum E58 were tested for their ability to enhance peroxide bleaching of Douglas-fir (Pseudotsuga menziesii) kraft pulp. A treatment with Irgazyme caused a much larger increase in brightness than did xylanase D. A double xylanase treatment with Irgazyme, before and after peroxide bleaching, resulted in the highest final brightness. Alkaline extraction increased the brightness of Douglas-fir brownstock. Treatment with Irgazyme released more lignin and carbohydrates than did xylanase D. The molecular mass of the lignin extracted from Irgazyme-treated brownstock was much larger than that from the control pulp. The lignin-like macromolecules directly solubilized from peroxide bleached pulps were substantially larger than those solubilized from the brownstock, irrespective of whether they were produced during xylanase or control treatments. This indicates that different kinds of materials were solubilized when a xylanase treatment was applied at different points in the bleaching sequence and raises concerns about the role of lignin entrapment in the mechanism by which xylanase enhances peroxide bleaching.

Antibacterial Ag/a-C nanocomposite coatings: The influence of nano-galvanic a-C and Ag couples on Ag ionization rates

Biofilm formation has been pointed as a major concern in different industrial applications, namely on biomedical implants and surgical instruments, which has prompted the development of new strategies for production of efficient antimicrobial surfaces. In this work, nano âgalvanic couples were created to enhance the antibacterial properties of silver, by embedding it into amorphous carbon (a-C) matrix. The developed Ag/a-C nanocomposite coatings, deposited by magnetron sputtering, revealed an outstanding antibacterial activity against S.epidermidis, promoting a total reduction in biofilm formation with no bacteria counts in all dilution. The open circuit potential (OCP) tests in 0.9% NaCl confirmed that a-C shows a positive \OCP\ value, in contrast to Ag coating, thus enhancing the ionization of biocidal Ag+ due to the nano-galvanic couple activation. This result was confirmed by the inductively coupled plasma-optical emission spectroscopy (ICP-OES), which revealed a higher Ag ionization rate in the nanocomposite coating in comparison with the Ag coating. The surface of Ag/a-C and Ag coatings immersed in 0.9% NaCl were monitored by scanning electron microscopy (SEM) over a period of 24 hours, being found that the Ag ionization determined by ICP-OES was accompanied by an Ag nanoparticles coalescence and agglomeration in Ag/a-C coating.

The role of monocarboxylate transporters in 3-bromopyruvate effect in cancer cells

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Molecular e Saúde).

Single molecule simulation of diffusion and enzyme kinetics

This work presents a molecular-scale agent-based model for the simulation of enzymatic reactions at experimentally measured concentrations. The model incorporates stochasticity and spatial dependence, using diffusing and reacting particles with physical dimensions. We developed strategies to adjust and validate the enzymatic rates and diffusion coefficients to the information required by the computational agents, i.e., collision efficiency, interaction logic between agents, the time scale associated with interactions (e.g., kinetics), and agent velocity. Also, we tested the impact of molecular location (a source of biological noise) in the speed at which the reactions take place. Simulations were conducted for experimental data on the 2-hydroxymuconate tautomerase (EC 5.3.2.6, UniProt ID Q01468) and the Steroid Delta-isomerase (EC 5.3.3.1, UniProt ID P07445). Obtained results demonstrate that our approach is in accordance to existing experimental data and long-term biophysical and biochemical assumptions.

HPV- detección por técnicas de patología molecular

Se trabaja con materiales de citologías y biopsias de cervix uterino en un grupo de pacientes controles biopsiados por otras sospechas clínicas sin diagnóstico clínico, colposcópico ni citológico de presunción de infección por HPV, y tres grupos de pacientes problemas, scorizados como presuntamente negativos, presuntamente sospechosos y presuntamente infectados, basados en presencia de cortes histológicos de acantosis, hiperplasia de células basales y asas capilares, coilocitorisis, cambios nucleares, binucleación y disqueratosis. Se correlacionan las biopsias con los estudios citológicos; sobre los cortes histológicos se procede a efectuar técnicas de hibridización in situ con sondas Innogenex para los virus 6-11, 6-18, grupo del 30. Se han estudiado las asociaciones del HPV en cervix con otras patologías (especialmente infecciosas) en nuestro medio, lesiones simuladoras de infección por el HPV y se trabajará en los grupos sospechosos y presuntamente infectados que sean positivos para la HIS, con marcaciones de detección de grado de actividad proliferativa para Mib1 y p53 y su relación con los subtipos virales. En las lesiones intraepiteliales relacionadas con el HPV se investigarán en la lesión y en la mucosa vecina receptores estrogénicos y progestacionales para tratar de determinar si la infección viral afecta la expresión de estos receptores.