9 documents found, page 1 of 1
Counteracting Colon Cancer by Inhibiting Mitochondrial Respiration and Glycolys...
Bessa, Cláudia; Loureiro, Joana B.; Barros, Matilde; Isca, Vera M. S.; Sardão, Vilma A.; Oliveira, Paulo J.; Bernardino, Raquel L.Metabolic reprogramming is a central hub in tumor development and progression. Therefore, several efforts have been developed to find improved therapeutic approaches targeting cancer cell metabolism. Recently, we identified the 7a-acetoxy-6b-benzoyloxy-12-O-benzoylroyleanone (Roy- Bz) as a PKC -selective activator with potent anti-proliferative activity in colon cancer by stimulating a PKC -dependent mitochondr...
Pro-Inflammatory Cytokines Trigger the Overexpression of Tumour-Related Splice ...
Pereira, Joana F. S.; Bessa, Cláudia; Matos, Paulo; Jordan, PeterSimple Summary: Tumours are now known to develop more quickly when the tumour cell mass is located in a tissue that shows signs of chronic inflammation. Under such conditions, inflammatory cells from the surrounding tumour microenvironment provide survival signals to which cancer cells respond. We have previously found that some colorectal tumours overexpress the protein RAC1B that sustains tumour cell survival...
A inflamação intestinal como promotor da tumorigénese: pistas sobre a base mole...
Pereira, Joana F.S.; Bessa, Cláudia; Matos, Paulo; Jordan, PeterA inflamação intestinal é uma doença crónica debilitante de origem multifatorial que afeta cerca de 25 000 portugueses. É também uma condição promotora para a tumorigénese no cólon. Um microambiente inflamatório fornece sinais de sobrevivência para as células cancerígenas, as quais respondem com mudanças no seu programa genético. RAC1B é um exemplo de um biomarcador que foi identificado num subconjunto de tumor...
A pro-inflammatory microenvironment triggers overexpression of tumor-related RA...
Pereira, Joana; Bessa, Cláudia; Gonçalves, Vânia; Matos, Paulo; Jordan, PeterUnderstand how tumor cells respond to a pro-inflammatory microenvironment with changes in the alternative splicing of RAC1B.
Exploring the effect of the pro-inflammatory microenvironment on the expression...
Bessa, Cláudia; Pereira, Joana Filipa de SousaAn inflammatory tumor cell microenvironment has been identified as a critical tumor-promoting condition providing survival signals to which cancer cells respond with changes in their gene expression. Interestingly, alternative splicing (AS) is one key gene regulatory mechanism that responds to extracellular signals directly affecting cancer progression. For example RACB1, a RAC1 AS variant, previously identifie...
Targeting tumour-related alternative splice variant RAC1B with anti-sense oligo...
Bessa, Cláudia; Gonçalves, Vânia; Jordan, PeterOver 90% of human protein coding genes are able to generate more than one transcript due to alternative splicing. In cancer, certain alternative splicing variants are frequently overexpressed and contribute to tumour progression and aggressiveness. This is well illustrated by RAC1B, a variant of the small GTPase RAC1 that is overexpressed in tumours from colon, breast, lung, pancreas and thyroid. RAC1B is gener...
Alternative Splicing: Expanding the Landscape of Cancer Biomarkers and Therapeu...
Bessa, Cláudia; Matos, Paulo; Jordan, Peter; Gonçalves, VâniaAlternative splicing (AS) is a critical post-transcriptional regulatory mechanism used by more than 95% of transcribed human genes and responsible for structural transcript variation and proteome diversity. In the past decade, genome-wide transcriptome sequencing has revealed that AS is tightly regulated in a tissue- and developmental stage-specific manner, and also frequently dysregulated in multiple human can...
Discovery of a small-molecule protein kinase Cδ-selective activator with promis...
Bessa, Cláudia; Soares, Joana; Raimundo, Liliana; Loureiro, Joana B.; Gomes, Célia; Reis, Flávio; Soares, Miguel L.; Santos, Daniel; Dureja, ChetnaProtein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (R...
Reactivation of wild-type and mutant p53 by tryptophanolderived oxazoloisoindol...
Soares, Joana; Raimundo, Liliana; Pereira, Nuno A. L.; Monteiro, Ângelo; Gomes, Sara; Bessa, Cláudia; Pereira, Clara; Queiroz, Glória; Bisio, AlessandraRestoration of the p53 pathway, namely by reactivation of mutant (mut) p53, represents a valuable anticancer strategy. Herein, we report the identification of the enantiopure tryptophanol-derived oxazoloisoindolinone SLMP53-1 as a novel reactivator of wild-type (wt) and mut p53, using a yeast-based screening strategy. SLMP53-1 has a p53-dependent anti-proliferative activity in human wt and mut p53R280K-expressi...