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A first-in-class inhibitor of homologous recombination DNA repair counteracts t...
Calheiros, Juliana; Silva, Rita; Barbosa, Filipa; Morais, João; Moura, Sara Reis; Almeida, Sofia; Fiorini, Elena; Mulhovo, Silva; Aguiar, Tatiana QuintaBackground Pancreatic ductal adenocarcinoma (PDAC) is among the cancer types with poorest prognosis and survival rates primarily due to resistance to standard-of-care therapies, including gemcitabine (GEM) and olaparib. Particularly, wild-type (wt)BRCA tumours, the most prevalent in PDAC, are more resistant to DNA-targeting agents like olaparib, restraining their clinical application. Recently, we disclosed a m...
MicroRNA-mediated control of mesenchymal stem/stromal cell senescence: A compar...
Giestinhas, Andrea; Moura, Sara Reis; Silva, Elsa; Nascimento, Diana; Almeida, Maria InêsOsteoarthritis is a growing health problem, aggravated by aging. Mesenchymal stem/stromal cells (MSCs) emerged as a promising cell-based therapy for this disease. However, in vitro expansion of MSCs can result in cell senescence. MicroRNAs (miRNAs) are key regulators of senescence pathways, making them attractive targets to decrease senescence. This work aims to identify senescence-related miRNAs, with the long...
Targeting p53 for Melanoma Treatment: Counteracting Tumour Proliferation, Disse...
Loureiro, Joana B.; Raimundo, Liliana; Calheiros, Juliana; Carvalho, Carla; Barcherini, Valentina; Lima, Nuno R.; Gomes, Célia; Almeida, Maria InêsMelanoma is the deadliest form of skin cancer, primarily due to its high metastatic propensity and therapeutic resistance in advanced stages. The frequent inactivation of the p53 tumour suppressor protein in melanomagenesis may predict promising outcomes for p53 activators in melanoma therapy. Herein, we aimed to investigate the antitumor potential of the p53-activating agent SLMP53-2 against melanoma. Two- and...
Targeting p53 for melanoma treatment: counteracting tumour proliferation, disse...
Loureiro, Joana B.; Raimundo, Liliana; Calheiros, Juliana; Carvalho, Carla; Barcherini, Valentina; Lima, Nuno R.; Gomes, Célia; Almeida, Maria InêsMelanoma is the deadliest form of skin cancer, primarily due to its high metastatic propensity and therapeutic resistance in advanced stages. The frequent inactivation of the p53 tumour suppressor protein in melanomagenesis may predict promising outcomes for p53 activators in melanoma therapy. Herein, we aimed to investigate the antitumor potential of the p53-activating agent SLMP53-2 against melanoma. Two- and...
SLMP53-2 Restores Wild-Type-Like Function to Mutant p53 through Hsp70: Promisin...
Gomes, Sara; Bosco, Bartolomeo; Loureiro, Joana B.; Ramos, Helena; Raimundo, Liliana; Soares, Joana; Nazareth, Nair; Barcherini, ValentinaHalf of human cancers harbor TP53 mutations that render p53 inactive as a tumor suppressor. In these cancers, reactivation of mutant p53 (mutp53) through restoration of wild-type-like function constitutes a valuable anticancer therapeutic strategy. In order to search for mutp53 reactivators, a small library of tryptophanol-derived oxazoloisoindolinones was synthesized and the potential of these compounds as mut...
SLMP53-2 Restores Wild-Type-Like Function to Mutant p53 through Hsp70: Promisin...
Gomes, Sara; Bosco, Bartolomeo; Loureiro, Joana B.; Ramos, Helena; Raimundo, Liliana; Soares, Joana; Nazareth, Nair; Barcherini, ValentinaHalf of human cancers harbor <i>TP53</i> mutations that render p53 inactive as a tumor suppressor. In these cancers, reactivation of mutant p53 (mutp53) through restoration of wild-type-like function constitutes a valuable anticancer therapeutic strategy. In order to search for mutp53 reactivators, a small library of tryptophanol-derived oxazoloisoindolinones was synthesized and the potential of these compounds...
Detection of the Epstein-Barr virus in blood and bone marrow mononuclear cells ...
Marques, Herlander; Catarino, Raquel; Domingues, Nelson; Barros, Eliane; Portela, Catarina; Almeida, Maria Inês; Costa, Sandra; Reis, R. M.The Epstein-Barr virus (EBV) is associated with a large spectrum of lymphoproliferative diseases. Traditional methods of EBV detection include the immunohistochemical identification of viral proteins and DNA probes to the viral genome in tumoral tissue. The present study explored the detection of the EBV genome, using the BALF5 gene, in the bone marrow or blood mononuclear cells of patients with diffuse large B...
Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in ...
Le, Xiao-Fen; Almeida, Maria Inês; Mao, Weiqu; Spizzo, Riccardo; Rossi, Simona; Nicoloso, Milena S.; Zhang, Shu; Wu, Yun; Calin, George A.Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER2 oncoprotein, can effectively target HER2-positive breast cancer through several mechanisms. Although the effects of trastuzumab on cancer cell proliferation, angiogenesis and apoptosis have been investigated in depth, the effect of trastuzumab on microRNA (miRNA) has not been extensively studied. We have performed...
microRNAs in Cancer: biological effects of microRNAs in colorectal cancer
Almeida, Maria InêsNon-coding RNAs are a class of RNA transcripts that do not codify for protein. Included in this class are the microRNAs, small RNAs with approximately 20 nucleotides in length. microRNAs act post-transcriptionally by binding to 5´- ultraconserved regions, coding regions or 3´-ultraconserved regions of messenger RNAs and inhibit its translation or cause messenger RNA cleavage. Additionally, microRNAs can also bi...
Association between EGF +61 genetic polymorphisms and non-small cell lung cance...
Mello, Ramon Andrade de; Ferreira, Mónica; Costa, Sandra; Costa, Bruno Marques; Pires, Filipa Soares; Neves, Inês; Almeida, Maria Inês; Cunha, JoãoEpidermal growth factor (EGF) and its receptor play critical roles in non-small cell lung cancer (NSCLC) carcinogenesis. A functional polymorphism in the EGF gene has been linked to increased cancer susceptibility. This study aimed to evaluate the role of the EGF +61A/G polymorphism as risk factors in NSCLC patients. For the present case-control study, we analyzed 112 NSCLC and 126 cancer-free controls from Por...