Percorrer por autor "Martins, Diana"
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- An update on the role of immune checkpoint inhibitors in lung cancer: a narrative systematic reviewPublication . Sousa, Inês; Martins, Diana; Mendes, FernandoIntroduction: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, and its aggressive nature necessitates the development of alternative therapeutic strategies. Immune checkpoint inhibitors (ICIs) have shown remarkable success in LC treatment. Despite advances with programmed cell death protein-1/programmed cell death ligand-1 inhibitors, many patients experience limited or short-lived responses, prompting interest in novel ICIs such as T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domain (TIGIT), lymphocyte-activation gene 3 (LAG-3), and indoleamine 2,3-dioxygenase 1 (IDO-1). Objectives: This narrative systematic review aimed to assess the clinical efficacy and safety of these novel ICIs compared to standard ICI therapy in LC. Methods: A systematic literature search was conducted across PubMed, Web of Science, and ClinicalTrials.gov. The search covered studies published from January 2020 to January 2025, to identify randomized controlled trials (RCTs) evaluating novel ICIs in LC. Due to substantial heterogeneity in study design, intervention targets, and outcome reporting, findings were synthesized narratively in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using RoB 2. Results: Five RCTs involving a total of 825 patients were included. TIGIT inhibition demonstrated benefit in progression-free survival and response rate. LAG-3 inhibitors showed mixed efficacy, with potential dose-related differences. IDO-1 inhibitors failed to improve outcomes compared with standard ICI. Reporting quality varied, with concerns regarding incomplete outcome data in some trials. Conclusion: These findings suggest promise for novel ICIs but are limited by small study numbers, methodological bias, and clinical heterogeneity. Larger, well-designed Phase III trials are required to validate these results.
- Crescent-like lesions as an early signature of nephropathy in a rat model of prediabetes induced by a hypercaloric dietPublication . Nunes, Sara; Alves, André; Preguiça, Inês; Barbosa, Adelaide; Vieira, Pedro; Mendes, Fernando; Martins, Diana; Viana, Sofia; Reis, FlávioDiabetic nephropathy (DN) is a major microvascular complication of diabetes. Obesity and hyperlipidemia, fueled by unhealthy food habits, are risk factors to glomerular filtration rate (GFR) decline and DN progression. Several studies recommend that diabetic patients should be screened early (in prediabetes) for kidney disease, in order to prevent advanced stages, for whom the current interventions are clearly inefficient. This ambition greatly depends on the existence of accurate early biomarkers and novel molecular targets, which only may arise with a more thorough knowledge of disease pathophysiology. We used a rat model of prediabetes induced by 23 weeks of high-sugar/high-fat (HSuHF) diet to characterize the phenotype of early renal dysfunction and injury. When compared with the control animals, HSuHF-treated rats displayed a metabolic phenotype compatible with obese prediabetes, displaying impaired glucose tolerance and insulin sensitivity, along with hypertriglyceridemia, and lipid peroxidation. Despite unchanged creatinine levels, the prediabetic animals presented glomerular crescent-like lesions, accompanied by increased kidney Oil-Red-O staining, triglycerides content and mRNA expression of IL-6 and iNOS. This model of HSuHF-induced prediabetes can be a useful tool to study early features of DN, namely crescent-like lesions, an early signature that deserves in-depth elucidation.
- Curcumins-Loaded ZIF-8 Nanoparticles-Embedded Transdermal Polymeric Patches Increase Apoptosis and Reduce Necrosis in a Dose-Dependent Manner in MCF-7 CellsPublication . Kiyak-Kirmaci, Humeysa; Aydin, Saliha; Yekeler, Humeyra Betul; Guler, Ece; Kayaci, Ayse Beyza; Gurer, Zeynep; Yilmaz-Goler, Ayse Mine; Erkmen, Ziya Engin; Duygulu, Ozgur; Bostan, Muge Sennaroglu; Martins, Diana; Mendes, Fernando; Eroglu, Mehmet Sayip; Edirisinghe, Mohan; Cam, Muhammet EminCurcumin(Cur)-loaded zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (Cur@ZIF-8 NPs) were produced to increase the anticancer activity of Cur. Cur@ZIF-8 NPs were embedded in polycaprolactone (PCL) fibers as transdermal polymeric patches via a pressured gyration (PG) method to provide controlled release. Cur@ZIF-8 NPs and Cur@ZIF-8 NPs-embedded PCL fibers were characterized for physical, chemical, mechanical, and thermal properties, also biological activities were examined with in vitro tests. Cur@ZIF-8 NPs were produced homogeneously with a size of ∼200 nm and a zeta potential of ∼−19 mV. Cur had better stability inside Cur@ZIF-8 NPs than its powder form. Cur@ZIF-8 NPs were successfully loaded in PCL fibers with a size of∼7 µm, and Cur@ZIF-8 NPs were dispersed amorphously in fibers. Cur was released in a controlled manner, and its efficiency was increased in the acidic microenvironment that is characteristic of cancer. Cur@ZIF-8 NPs have more bioavailability than powdered Cur and can penetrate the cells to deliver their anticancer effects on MCF-7 human breast cancer cells. Cur@ZIF-8 NPs-embedded transdermal polymeric patches promote apoptosis in MCF-7 cells by reducing necrosis, particularly under acidic conditions. This work presents a release system with synergistic anticancer effects, offering a novel approach for Cur’s clinical application in breast cancer through enhanced targeting.
- O Ecomuseu da Identidade e Memória TirsensePublication . Martins, DianaNa década de 1970 inicia-se uma nova tipologia museológica, capaz de incluir a sociedade, o meio envolvente e as organizações que relacionam com a comunidade local. Os ecomuseus passam, portanto, a ser adotados como um modelo de museologia integrativa que permite o desenvolvimento do meio envolvente onde se insere. Neste sentido o seguinte trabalho adapta este modelo ao contexto do concelho de Santo Tirso, integrando temáticas relacionadas com a identidade tirsense e memória tirsense, através do desenvolvimento de uma proposta de criação de um ecomuseu. Dentro da metodologia, inicialmente são abordados alguns temas conceptuais que serão importantes para definir a proposta do ecomuseu. Uma vez que a temática principal proposta para o ecomuseu relaciona-se com a identidade tirsense, desenvolve-se alguns dos tópicos principais que contribuem para esta identidade como é o caso da agricultura, da indústria têxtil e dos produtos locais. Para além disso, desenvolve-se o contexto daquele que foi o local elegido para sediar o ecomuseu, a antiga casa dos lagareiros da Quinta de Gião, junto ao rio Sanguinhedo e ao lugar da Ponte Velha em Santo Tirso, na qual consta um antigo lagar de azeite que se pretende reabilitar. Relativamente ao trabalho de campo surge no contexto de entrevistas realizadas com a comunidade local, com os stakeholders e com profissionais da área da museologia. Por último é apresentada a proposta efetiva do ecomuseu e de algumas atividades que se pretende ver incluídas na oferta cultural do museu.
- Immunotherapy in penile cancer: a systematic reviewPublication . Fadigas, Filipe; Martins, Diana; Mendes, FernandoPenile cancer (PeCa) ranks as the 30th most prevalent cancer globally, predominantly affecting populations in developing countries. Phimosis and Human Papillomavirus (HPV) infection are recognized as the primary risk factors. Early-stage diagnosis typically warrants limited excision or non-invasive therapies. However, recent research into the carcinogenesis tumour microenvironment, and the role of the host immune system in its development suggests that immunotherapy could be a promising treatment for PeCa. The rarity of the disease, combined with the success of standard treatments and the fact that many patients in clinical trials lack alternative options, contributes to the challenges in patient recruitment for these studies. Additionally, the psychological burden stemming from the stigma associated with such an aggressive genital disease and the preference for quicker treatment options, such as surgery with reconstructive procedures, exacerbates these recruitment difficulties. This systematic review aimed to explore various immunotherapy approaches in treating PeCa to elucidate the potential role of immunotherapy in this context. The literature was sourced from freely accessible, full-text randomized controlled trials, non-randomized controlled trials, and original articles published in English between 2017 and 2023. Eligible clinical trials were required to be in phase 2 and have published results. Although only one study met the inclusion criteria—a significant limitation—the objective response rate recorded was 6% across nineteen patients with different tumour histologies, of which only six had PeCa. Currently, other studies are either recruiting or ongoing, necessitating further observation, as results from a single study cannot be generalized to the broader population.
- Microbiome and response to therapy in triple negative breast cancer: a systematic reviewPublication . Lopes, Mariana; Vila Nova, Carlos; Oliveira, Rui Caetano; Schmitt, Fernando; Mendes, Fernando; Martins, DianaObjectives: Triple-negative breast cancer (TNBC) accounts for approximately 15% of all invasive breast cancers and is characterized by aggressive behavior, limited therapeutic options, and poor clinical outcomes. Due to the absence of hormone receptors and HER2 expression, systemic treatment relies predominantly on chemotherapy, which is associated with high rates of early recurrence and mortality. Emerging evidence suggests that alterations in the microbiome can contribute to TNBC progression and influence therapeutic response, particularly affecting the efficacy of chemotherapy and immunotherapy through immune-mediated mechanisms; however, its role in TNBC remains incompletely understood. This systematic review aims to explore the role of the microbiome in TNBC. It specifically aims to understand if the microbiome influences complete pathological response in TNBC. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed in PubMed and Cochrane databases. Fourteen eligible studies were included, encompassing preclinical and clinical evidence. Results: The findings indicate that both gut and tumor-associated microbiota significantly influence therapeutic response in TNBC, especially in the context of neoadjuvant chemotherapy (NACT) and immune checkpoint blockade (ICB). Higher microbial diversity and the presence of specific commensal taxa were consistently associated with enhanced antitumor immune activation, increased immune cell infiltration, and improved treatment efficacy. Conversely, antibiotic-induced dysbiosis was linked to reduced pCR rates and poorer clinical outcomes. Microbiome-modulating interventions demonstrated potential in restoring eubiosis and enhancing therapeutic responsiveness. Conclusions: Overall, the available evidence supports the microbiome as a promising biomarker and therapeutic target for optimizing treatment strategies and improving outcomes in TNBC
- The role of the gut microbiome in clinical outcomes of colorectal cancer: a systematic review (2020–2025)Publication . Santos, Iara; Liberal, Joana; Teixeira, Paulo; Martins, Diana; Mendes, FernandoABSTRACT: Background: The Colorectal Cancer (CRC) pathogenesis and therapeutic efficacy are influenced by the gut microbiome, making it a promising biomarker for predicting treatment responses and adverse effects. This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes. Methods: Key studies investigating the microbiome’s role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025, respectively. Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes. RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies, respectively. Data extracted was narratively analyzed. Results: Six studies involving a total of 361 individuals were included. Therapeutic interventions, either standard treatments and/or those targeting the gut microbiome, generally increased probiotic taxa and reduced pro-carcinogenic bacteria. However, no consistent pattern of improved clinical outcomes was observed, suggesting that treatment mechanisms, the tumor’s nature, and individual characteristics play critical roles in microbiome modulation. Conclusion: The gut microbiome holds significant potential in clinical settings. Nonetheless, further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms, the tumor’s nature, and individual characteristics as modulators, in order to optimize clinical outcomes
- The effect of nutritional intervention in nutritional risk screening on hospitalised lung cancer patientsPublication . Oliveira, Raquel; Cabrita, Bruno; Cunha, Ângela; Silva, Sónia; PM Lima, João; Martins, Diana; Mendes, FernandoAbstract: Background: Lung cancer (LC) patients are prone to suffer from malnutrition. Malnutrition negatively affects patients’ response to therapy, increases the incidence of treatment-related side effects, and decreases survival. Early identification of LC patients who are malnourished or at risk of malnutrition can promote recovery and improve prognosis. Objective: This study aimed to assess the risk and nutritional status of lung cancer patients who are hospitalised, as well as to evaluate the impact of nutritional intervention on the risk of malnutrition. Methods: From January 2022 to December 2023, 53 LC patients hospitalised in a pulmonology department had their nutritional risk (initial and final) and nutritional status (initial) assessed. All were selected for nutritional intervention. Nutrition counselling was the first intervention option, along with dietary changes with/without oral nutritional supplements. Results: At the time of hospitalisation, 90.6% of the patients were at nutritional risk, 45.3% were classified as moderately malnourished, and 35.8% were classified as severely underweight. After the hospitalisation, 73.6% were at nutritional risk at the time of discharge, suggesting a statistically significant decrease in the number of patients with nutritional risk. Conclusions: Most LC patients hospitalised presented an altered nutritional status. Our study suggests that a nutritional intervention must be implemented to reduce malnutrition risk, which may impact prognosis. The comprehensive nutritional problems experienced by LC patients require nutritional assessment and improved individually tailored nutritional support.
- The role of immune checkpoint blockade in acute myeloid leukemiaPublication . Silva, Margarida; Martins, Diana; Mendes, FernandoImmune checkpoint inhibition (ICI) has emerged as a therapeutic option for acute myeloid leukemia (AML) for patients that suffer from relapsed or high-risk disease, or patients ineligible for standard therapy. We aimed to study ICI as monotherapy and/or combined therapy (with chemotherapy (QT), for AML patients. The PRISMA statement was used. The literature used comprised clinical trials, randomized controlled trials, and systematic reviews published within the last 7 years. The blockade of CTLA-4 presented a 42% of complete remission within AML. Nivolumab in high-risk AML showed a median recurrence-free survival (RFS) of 8.48 months. The same drug on relapsed hematologic malignancies after allogenic transplantation shows a 1-year OS of 56%. The use of prophylaxis post allogenic transplantation cyclophosphamide (PTCy), following checkpoint inhibition, demonstrated different baseline disease and transplantation characteristics when compared to no-PCTy patients, being 32% and 10%, respectively. CTLA-4 blockage was a worthy therapeutic approach in relapsed hematologic malignancies, presenting long-lasting responses. The approach to AML and myelodysplastic syndrome patients with ICI before allogenic hematopoietic stem cell transplantation and the use of a graft-versus-host disease prophylaxis have shown improvement in the transplantation outcomes, and therefore AML treatment.
- Unveiling the anticancer potential of urolithin A in colorectal cancer: a systematic reviewPublication . Francisco, Mariana; Mendes, Fernando; Martins, Diana; Liberal, JoanaObjectives: Colorectal cancer (CRC) is a major global health burden, and Urolithin A (Uro-A) has emerged as a promising anticancer agent. This systematic review aims to synthesize current in vitro evidence on the anticancer effects of Uro-A in CRC, highlighting effective concentration ranges, exposure times, relevant outcomes, and underlying molecular mechanisms. Methods: Following PRISMA 2020 guidelines, a systematic search was conducted in PubMed, Scopus, and Web of Science using the following strategy: (colorectal cancer) AND (urolithin a) OR (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one). Eligibility criteria were defined by the PICO framework: (P) in vitro CRC cell models; (I) Uro-A alone or combined treatments; (C) No intervention, vehicle or other treatments; (O) Relevantanticancer outcomes of Uro-A in CRC. Only original, full-text, in vitro studies in English were included. Risk of bias was assessed using ToxRTool. A qualitative synthesis was performed due to the heterogeneity of the included studies. Results: Fifteen studies met inclusion criteria, involving CRC cell lines (Caco-2, HCT-116, HT-29, SW480, SW620) and normal colon fibroblasts (CCD18-Co). Uro-A inhibited CRC cell proliferation, clonogenic growth, cancer stem cells properties, migration, and invasion, and induced cell cycle arrest, apoptosis, autophagy, and senescence, through modulation of key signaling pathways and proteins. Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects. Discussion: The findings support Uro A’s potential as a preventive or adjuvant agent in CRC treatment. However, preclinical nature of the evidence and methodological heterogeneity hinder clinical extrapolation to in vivo contexts. Human clinical trials are necessary to overcome these limitations. Other: This review was registered in PROSPERO (CRD420251070874) and supported by FCT/MCTES UIDP/05608/2020 and UIDB/05608/2020. Institutional.