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- Prostate cancer: antitumor effect of chalcones on androgen dependent and androgen-independent prostate cancer cell linesPublication . Horta, Bruno; Cerqueira, Fátima; Pinto, Madalena; Cidade, Honorina; Silva, Jani; Pereira, António; Medeiros, R.
- Omega 3 and resveratrol loaded lipid nanosystems for potential use as topical formulations in autoimmune, inflammatory, and cancerous skin diseasesPublication . Caldas, Ana Rita; Catita, José; Machado, Raúl; Ribeiro, Artur; Cerqueira, Fátima; Horta, Bruno; Medeiros, R.; Lúcio, Marlene; Lopes, Carla MartinsResveratrol (RSV) and omega 3 (ω3), because of their biological favorable properties, have become subjects of interest for researchers in dermocosmetic and pharmaceutical industries; however, these bioactives present technological limitations that hinder their effective delivery to the target skin layer. To overcome the stability and skin permeation limitations of free bioactives, this work proposes a combined strategy involving two different lipid nanosystems (liposomes and lipid nanoparticles) that include ω3 in their lipid matrix. Additionaly, RSV is only encapsulated in liposomes that provid an adequate amphiphilic environment. Each formulation is thoroughly characterized regarding their physical–chemical properties. Subsequently, the therapeutic performance of the lipid nanosystems is evaluated based on their protective roles against lipid peroxidation, as well as inhibition of cicloxygenase (COX) and nitric oxid (NO) production in the RWA264.7 cell line. Finally, the lipid nanosystems are incorporated in hydrogel to allow their topical administration, then rheology, occlusion, and RSV release–diffusion assays are performed. Lipid nanoparticles provide occlusive effects at the skin surface. Liposomes provide sustained RSV release and their flexibility conferred by edge activator components enhances RSV diffusion, which is required to reach NO production cells and COX cell membrane enzymes. Overall, the inclusion of both lipid nanosystems in the same semisolid base constitutes a promising strategy for autoimmune, inflammatory, and cancerous skin diseases.
- Cervical cancer outcome and tumor-associated macrophages: research evidencePublication . Horta, Bruno; Pereira, Tomé; Medeiros, R.; Cerqueira, FátimaInflammation is a key factor in cancer promotion. Tumor-associated macrophages (TAMs), as part of the tumor microenvironment, are often associated with the progression of tumors and a worse prognosis in many cancers, namely on cervical cancer. This work exhaustively summarizes the conclusions of the different studies published concerning TAMs function in cervical cancer, from in vitro studies using cancer cell lines to the clinical perspective (histological samples-based studies). Most studies have led to the conclusion that TAMs increased density is directly related to increased severity of a malignant cervical lesion. Additionally, TAMs are normally polarized into an M2 phenotype, benefiting and promoting tumor progression, resulting in a worse disease outcome. The tumor microenvironment is also a highly critical contributor that not only influences tumor natural history but also modulates the specific immune response.
- Effect of heptaphylline and two related secondary metabolites on cervical (HeLa) and prostate (LNCaP and PC-3) cancer cell linesPublication . Horta, Bruno; Cerqueira, Fátima; Pinto, Madalena; Sousa, Emília; Puthongking, Ploenthip; Pereira, António; Medeiros, R.
- Effect of 1-carbaldehyde-3,4-dimethoxyxanthone on prostate and HPV-18 positive cervical cancer cell lines and on human THP-1 macrophagesPublication . Medeiros, R.; Horta, Bruno; Freitas-Silva, Joana; Silva, Jani; Dias, Francisca; Sousa, Emília; Pinto, Madalena; Cerqueira, FátimaXanthone derivatives have shown promising antitumor properties, and 1-carbaldehyde-3,4- dimethoxyxanthone (1) has recently emerged as a potent tumor cell growth inhibitor. In this study, its effect was evaluated (MTT viability assay) against a new panel of cancer cells, namely cervical cancer (HeLa), androgen-sensitive (LNCaP) and androgen-independent (PC-3) prostate cancer, and nonsolid tumor derived cancer (Jurkat) cell lines. The effect of xanthone 1 on macrophage functions was also evaluated. The effect of xanthone 1-conditioned THP-1 human macrophage supernatants on the metabolic viability of cervical and prostate cancer cell lines was determined along with its interference with cytokine expression characteristic of M1 profile (IL-1 ≤ β; TNF-α) or M2 profile (IL-10; TGF-β) (PCR and ELISA). Nitric oxide (NO) production by murine RAW264.7 macrophages was quantified by Griess reaction. Xanthone 1 (20 µM) strongly inhibited the metabolic activity of the cell lines and was significantly more active against prostate cell lines compared to HeLa (p < 0.05). Jurkat was the cell most sensitive to the effect of xanthone 1. Compound 1-conditioned IL-4-stimulated THP-1 macrophage supernatants significantly (p < 0.05) inhibited the metabolic activity of HeLa, LNCaP, and PC-3. Xanthone 1 did not significantly affect the expression of cytokines by THP-1 macrophages. The inhibiting effect of compound 1 observed on the production of NO by RAW 264.7 macrophages was moderate. In conclusion, 1-carbaldehyde-3,4-dimethoxyxanthone (1) decreases the metabolic activity of cancer cells and seems to be able to modulate macrophage functions.