TOXICOLOGIC PATHOLOGY LAB

ABOUT

MAIN ACHIEVEMENTES

TOP PAPERS 2018-2023

RESEARCH TEAM

CURRENT PROJECTS

PUBLICATIONS

SERVICES

Sara Ricardo

Director

ABOUT

Under construction.

tp-ucibio-1htoxrun@iucs.cespu.pt

MAIN ACHIEVEMENTS

Generation of drug-resistant cellular models. We generated two HGSC cell lines with induced PTX resistance and P-gp overexpression suitable to test new and more effective P-gp inhibitors (https://doi.org/10.3389/fonc.2021.752127). Moreover, since OVCAR 8 has intrinsic Carboplatin resistance, our two OVCAR8 Paclitaxel resistant models are also suitable to test the efficacy of drugs to revert platinum-taxane resistance. The generation of powerful tools to study chemoresistance in an HGSC setting is crucial to discover effective drugs to treat double-resistant tumours. In the same line, we established an AML MDR subline – HL60-CDR – which presents several resistance mechanisms, providing an in vitro model to test new compounds to circumvent multi-drug resistance in myeloid leukaemia (https://doi.org/10.1080/1120009X.2022.2097432). Creating cellular models that mimic drug-induced changes is crucial for drug screening and to develop therapeutic strategies to overcome drug resistance.

Histology Based Approach to Evaluate Drug-Induced Alterations in Protein Expression. We developed a new histology-based method (cell microarray) to evaluate morphological changes and biomarker expression changes after drug exposure in cellular models (https://doi.org/10.36255/cell-microarray). Cell microarrays allow the analysis of several samples side by side on a single microscopic slide, minimizing the volume of reagents used and the biomarker evaluation in its cellular localization (e.g., nuclear, cytoplasm and membrane). Applied to drug-induced alterations, these cell microarrays can comprise multiple samples/conditions in a single histology block, allowing the evaluation of the phenotypic kinesis of cancer cell lines before and after exposure to different drugs and the identification of putative therapy response biomarkers.

The effect of high-fat and sugar-rich foods on cells and tissues. We evaluated the effects induced by the early consumption of high-sugar (HS) and high-energy diets (HED) on the liver and adipose tissue structure in male rats, addressing the contrasting effects of both unhealthy diets on metabolic function, local inflammation, and oxidative stress (https://doi.org/10.1007/s00418-022-02092-2). This study revealed the long-lasting negative effects of the consumption of HS and HED diets on liver, adipose tissue, and metabolic-related parameters, with HED leading to a more pronounced adiposity and distinct hepatic phenotype characterized by increased inflammation and oxidative stress.

TOP PAPERS 2018-2023

Nunes, M., Silva, P. M. A., Coelho, R., Pinto, C., Resende, A., Bousbaa, H., Almeida, G. M., & Ricardo, S. (2021). Generation of Two Paclitaxel-Resistant High-Grade Serous Carcinoma Cell Lines With Increased Expression of P-Glycoprotein. Frontiers in oncology, 11, 752127. https://doi.org/10.3389/fonc.2021.752127

Nunes, M., Nunes, D., & Ricardo, S. (2023). Cell Microarray: An Approach to Evaluate Drug-Induced Alterations in Protein Expression. In C. M. Sergi (Ed.), Advancements in Cancer Research. Exon Publications. https://doi.org/10.36255/cell-microarray

Nogueira, S., Garcez, F., Sá, S., Moutinho, L. C., Cardoso, A., Soares, R., Fonseca, B. M., & Leal, S. (2022). Early unhealthy eating habits underlie morpho-functional changes in the liver and adipose tissue in male rats. Histochemistry and cell biology, 157(6), 657–669. https://doi.org/10.1007/s00418-022-02092-2

RESEARCH TEAM

PhD Members

Cristina Xavier

Filipa Sobral

Graça Casal

Maria Begoña Criado

Maria do Céu Monteiro

Sandra Leal

Sara Ricardo

Sofia Nogueira

Collaborators

Albina Dolores Resende

Alexandra Viana da Costa

Carla Pinto

Kristof Raemdonck

Luís Pina Cabral

Maria João Neuparth

Paolo De Marco

Sandra Quinteira

PhD Students

Ana Catarina Sousa

Diana Nunes

Jéssica Fonseca

Marcio Gaspar

MSc Students

Under construction.

Research Fellowship

Under construction.

Volunteers

Under construction.

Research Technician

Under construction.

CURRENT PROJECTS

FCT (Portuguese Foundation for Science and Technology) FUNDED PROJECTS

PTDC/MEC-ONC/29503/2017_Blocking MUC16-mesothelin interaction to abrogate peritoneal metastization of ovarian cancer.

              
        Blocking MUC16-mesothelin interaction to abrogate peritoneal metastization of ovarian cancer.   
Principal Investigator: 
Leonor David
Leader Institution: 
--
Funding entity: 
FCT
Program: 
--
Budget: 
249.000,00€
Period covered: 
15-07-2018 to 14-12-2021
Abstract: 
--
Research Team: 
Sara Ricardo

PTDC/CTA-AMB/0853/2021_NIAF - Sustainable antifouling agents: from grape wastes to the sea with the green chemistry leading the way.

              
        Sustainable antifouling agents: from grape wastes to the sea with the green chemistry leading the way.   
Principal Investigator: 
Marta Correia da Silva (CIIMAR/FFUP)
Leader Institution: 
CIIMAR
Funding entity: 
FCT
Program: 
Concurso de Projetos de IC&DT em Todos os Domínios Científicos 2021
Budget: 
249.397,5 €
Period covered: 
01.01.2022 to 31.12.2024
Abstract: 
--
Research Team: 
Paolo De Marco, Maria Elizabeth Tiritan, Alexandra Maia, Virgínia Gonçalves

CESPU FUNDED PROJECTS

SPAinT_GI2-CESPU_2022 - Quantification of Pyrrolizidine Alkaloids in Infusions of Medicinal Plants and Food Supplements Available in the Portuguese Market .

              
        SPAinT - Quantification of Pyrrolizidine Alkaloids in Infusions of Medicinal Plants and Food Supplements Available in the Portuguese Market   
Principal Investigator: 
Sandra Leal
Leader Institution: 
TOXRUN-CESPU
Funding entity: 
CESPU
Program: 
GI2-CESPU-2022
Budget: 
4.500€
Period covered: 
01.09.2022 - 31.08.2023 
Abstract: 
The pyrrolizidine alkaloids (PAs) are a class of compounds of natural origin, found in some foods and in diverse plant families. These compounds may show acute and/or chronic toxicity when certain plants are consumed in high amounts or due to prolonged consumption of foods and medicinal plants containing reduced amounts of PAs. Among the most common routes of exposure to PAs is the consumption of infusions, herbal medicinal preparations and dietary supplements. In Portugal, there is no information on the occurrence of PAs in the various products available. The objective of this proposal is to determine the main herbal medicinal products used by the Portuguese population by online databases and survey and to quantify PAs in those products. This work will allow to determine the possible occurrence of PAs in products available in the Portuguese market and the possible risk of exposure for consumers. 
Research Team: 
Sandra Leal, Cláudia Ribeiro, Inês Pádua, Ana Sousa, Virgínia Gonçalves

CBToxAtOpi_GI2-CESPU_2022 - Cognitive-behavioral toxicity of atypical opioids – a molecular, biochemical and histopathological approach.

              
        Cognitive-behavioral toxicity of atypical opioids – a molecular, biochemical and histopathological approach  
Principal Investigator: 
Maria Joana Barbosa
Leader Institution: 
TOXRUN-CESPU
Funding entity: 
CESPU
Program: 
GI2-CESPU-2022
Budget: 
6.000€
Period covered: 
01.09.2022 - 31.08.2023 
Abstract: 
Tramadol and tapentadol are synthetic and atypical opioids, acting as mu-opioid agonists and monoamine reuptake inhibitors, which optimizes their analgesic and safety profile. However, they are not devoid of toxicological risk, being associated with several adverse reactions. Considering their frequent use on a chronic basis, the study of their potential cognitive-behavioral toxicity becomes pertinent. In this context, the present project aims to assess tramadol and tapentadol neuromodulator effects, from a molecular, biochemical and histopathological perspective. Hippocampus, pre-frontal cortex and nucleus accumbens samples from Wistar rats, administered with 50 mg/kg opioid within the scope of a previous project, will be used. Such brain structures will be characterized from a histopathological point of view. Gene expression of receptors and transcription factors, as well as metabolites implied in neurodegeneration, astroglial activation, and cognitive impairment, will be quantified. The results will provide data on pharmaceutical opioid effects on reward, memory, learning and adaptation mechanisms, in different brain structures, thus promoting a more conscientious prescription.
Research Team: 
Maria Joana Barbosa, Juliana Faria, Cristiana Cardoso, Fernanda Garcez, Ricardo Dinis, Sandra Leal

OVCARTEST_GI2-CESPU_2022 - Ovarian Cancer Ascites-Derived Organoids as a Preclinical Platform to Predict Therapeutical Responses

              
        Ovarian Cancer Ascites-Derived Organoids as a Preclinical Platform to Predict Therapeutical Responses  
Principal Investigator: 
Sara Ricardo
Leader Institution: 
CESPU
Funding entity: 
CESPU
Program: 
GI2-CESPU-2022
Budget: 
5.500€
Period covered: 
Abstract: 
Ascites (Greek meaning Askos) is an inflammatory process that induces the abnormal accumulation of fluid into the peritoneal cavity and is a common feature in advanced ovarian cancer (OC). In almost all patients, the recurrent disease is accompanied by the accumulation of ovarian cancer ascites (ASKOC) and is associated with chemoresistance and poor prognosis. ASKOC comprises a reservoir of a complex mixture of cellular and acellular components which provides a pro-inflammatory and tumor promoting microenvironment for cancer cells. The accessibility to ASKOC and its cellular components makes it a unique source to track tumor progression and a key element to overcome chemoresistance. The aim of this project is to use ASKOC tumor cells to produce patient-derived organoids that reflect chemoresistant phenotype and clinical responses. We plan to use ASKOC-derived organoids to create a personalized drug sensitivity and synergy test capable of guiding clinical decisions in a short-time frame. The development of patient-derived ex vivo drug tests capable of predicting drug responses constitutes an important step towards a personalized medicine.
Research Team: 
Sara Ricardo, Raquel Almeida, Diana Nunes, Mariana Nunes

upPTXovcar_GI2-CESPU_2022 - Overcoming paclitaxel resistance in ovarian cancer.

              
        Overcoming paclitaxel resistance in ovarian cancer  
Principal Investigator: 
Patrícia Silva
Leader Institution: 
CESPU
Funding entity: 
CESPU
Program: 
GI2-CESPU-2022
Budget: 
5.500€
Period covered: 
01.09.2022 - 31.08.2023 
Abstract: 
Paclitaxel is one of the most active chemotherapeutic agents used in cancer therapy. By targeting microtubules, paclitaxel induces a cell cycle arrest at mitosis followed by an expected cell death. However, development of resistance to paclitaxel profoundly impacts cancer outcomes by limiting the clinical benefit of cancer treatment. The research focus has been on unveiling promising therapeutic alternatives such as combinations between old cytotoxic agents and molecular-targets inhibitors. The identification of small molecules that may reverse the resistance phenotype of cancer cells and/or sensitize cancer cells to paclitaxel without undesirable side effects will be of great impact for clinical research. In the current study, and using PTX-resistant cell lines, we aim to identify, from a panel of mitotic inhibitors and apoptotic inducers, small molecule candidates that possess anti-cancer synergy with paclitaxel in order to overcome resistant phenotype in ovarian carcinoma and improve patient outcomes.
Research Team: 
Patrícia Silva, Hassan Bousbaa, Bárbara Pinto, João Silva, Mariana Nunes, Sara Ricardo

PUBLICATIONS

Almeida-Nunes, D. L., Silvestre, R., Dinis-Oliveira, R. J., & Ricardo, S. (2024). Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins. International Journal of Molecular Sciences, 25(1), 323. https://doi.org/10.3390/ijms25010323

Rocha, S., Alves, A., Antunes, C., Rodrigues, P., Casal, G. (2024) Characterization of novel aurantiactinomyxon types (Cnidaria, Myxosporea) from the oligochaete Ilyodrilus templetoni (Southern, 1909), with a comprehensive phylogeny of the collective group. Journal of Invertebrate Pathology 203: 108043. https://doi.org/10.1016/j.jip.2023.108043

Carraro, M.L., Marques, S., Silva, A.S., Freitas, B., Silva, P.M.A., Pedrosa, J., De Marco, P., Bousbaa, H., Fernandes, C., Tiritan, M.E., Silva, A.M.S., Pinto, M.M.M. (2020). Synthesis of New Chiral Derivatives of Xanthones with Enantioselective Effect on Tumor Cell Growth and DNA Crosslinking. ChemistrySelect 5 2020, , 10285 – 10291. doi.org/10.1002/slct.202002588

AFFILIATION

English affiliation:

- Associate Laboratory i4HB - Institute for Health and Bioeconomy, University Institute of Health Sciences - CESPU, 4585-116 Gandra, Portugal.

- UCIBIO - Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal.

Portuguese affiliation:

- Laboratório Associado i4HB - Instituto de Saúde e Bioeconomia, Instituto Universitário de Ciências da Saúde - CESPU, 4585-116 Gandra, Portugal.

- UCIBIO - Unidade de Biociências Moleculares Aplicadas, Laboratório de Investigação em Patologia Toxicológica, Instituto Universitário de Ciências da Saúde (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal.

SERVICES

Under construction.