Publications by authors named "R Henrique"

305 Publications

Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation.

Cancers (Basel) 2021 Apr 27;13(9). Epub 2021 Apr 27.

Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.

Despite the intensive efforts dedicated to cancer diagnosis and treatment, lung cancer (LCa) remains the leading cause of cancer-related mortality, worldwide. The poor survival rate among lung cancer patients commonly results from diagnosis at late-stage, limitations in characterizing tumor heterogeneity and the lack of non-invasive tools for detection of residual disease and early recurrence. Henceforth, research on liquid biopsies has been increasingly devoted to overcoming these major limitations and improving management of LCa patients. Liquid biopsy is an emerging field that has evolved significantly in recent years due its minimally invasive nature and potential to assess various disease biomarkers. Several strategies for characterization of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been developed. With the aim of standardizing diagnostic and follow-up practices, microfluidic devices have been introduced to improve biomarkers isolation efficiency and specificity. Nonetheless, implementation of lab-on-a-chip platforms in clinical practice may face some challenges, considering its recent application to liquid biopsies. In this review, recent advances and strategies for the use of liquid biopsies in LCa management are discussed, focusing on high-throughput microfluidic devices applied for CTCs and ctDNA isolation and detection, current clinical validation studies and potential clinical utility.
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http://dx.doi.org/10.3390/cancers13092101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123575PMC
April 2021

Differential methylation EPIC analysis discloses cisplatin-resistance related hypermethylation and tumor-specific heterogeneity within matched primary and metastatic testicular germ cell tumor patient tissue samples.

Clin Epigenetics 2021 Apr 6;13(1):70. Epub 2021 Apr 6.

Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.

Testicular germ cell tumors (TGCTs) are among the most common solid malignancies in young-adult men, and currently most mortality is due to metastatic disease and emergence of resistance to cisplatin. There is some evidence that increased methylation is one mechanism behind this resistance, stemming from individual studies, but approaches based on matched primary and metastatic patient samples are lacking. Herein, we provide an EPIC array-based study of matched primary and metastatic TGCT samples. Histology was the major determinant of overall methylation pattern, but some clustering of samples related to response to cisplatin was observed. Further differential analysis of patients with the same histological subtype (embryonal carcinoma) disclosed a remarkable increase in net methylation levels (at both promoter and CpG site level) in the patient with cisplatin-resistant disease and poor outcome compared to the patient with complete response to chemotherapy. This further confirms the recent results of another study performed on isogenic clones of sensitive and resistant TGCT cell lines. Differentially methylated promoters among groups of samples were mostly not shared, disclosing heterogeneity in patient tissue samples. Finally, gene ontology analysis of cisplatin-resistant samples indicated enrichment of differentially hypermethylated promoters on pathways related to regulation of immune microenvironment, and enrichment of differentially hypomethylated promoters on pathways related to DNA/chromatin binding and regulation. This data supports not only the use of hypomethylating agents for targeting cisplatin-resistant disease, but also their use in combination with immunotherapies and chromatin remodelers.
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http://dx.doi.org/10.1186/s13148-021-01048-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025580PMC
April 2021

Discovery of Volatile Biomarkers for Bladder Cancer Detection and Staging through Urine Metabolomics.

Metabolites 2021 Mar 26;11(4). Epub 2021 Mar 26.

UCIBIO/REQUIMTE, Department of Biological Sciences, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.

Timely diagnosis is crucial to improve the long-term survival of bladder cancer (BC) patients. The discovery of new BC biomarkers based in urine analysis is very attractive because this biofluid is in direct contact with the inner bladder layer, in which most of the neoplasms develop, and is non-invasively collected. Hence, this work aimed to unveil alterations in the urinary volatile profile of patients diagnosed with BC compared with cancer-free individuals, as well as differences among patients diagnosed at different tumor stages, to identify candidate biomarkers for non-invasive BC diagnosis and staging. Urine analysis was performed by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results unveiled that BC patients have a distinct urinary volatile profile characterized by higher levels of several alkanes and aromatic compounds, and lower levels of aldehydes, ketones and monoterpenes. Seventeen significantly altered volatiles were used to evaluate the performance for overall BC detection, disclosing 70% sensitivity, 89% specificity and 80% accuracy. Moreover, distinct urinary volatile profiles were found among patients diagnosed at different tumor stages (Ta/Tis, T1 and ≥T2). This work identified distinct urinary volatile signatures of BC patients with potential for non-invasive detection and staging of bladder cancer.
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http://dx.doi.org/10.3390/metabo11040199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066175PMC
March 2021

Urinary Extracellular Vesicles as Potential Biomarkers for Urologic Cancers: An Overview of Current Methods and Advances.

Cancers (Basel) 2021 Mar 26;13(7). Epub 2021 Mar 26.

IPO Porto Research Center (CBEG CI-IPOP), Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.

Urologic cancers are a heterogeneous group of tumors, some of which have poor prognosis. This is partly due to the unavailability of specific and sensitive diagnostic techniques and monitoring tests, ideally non- or minimally invasive. Hence, liquid biopsies are promising tools that have been gaining significant attention over the last decade. Among the different classes of biomarkers that can be isolated from biofluids, urinary extracellular vesicles (uEVs) are a promising low-invasive source of biomarkers, with the potential to improve cancer diagnosis and disease management. Different techniques have been developed to isolate and characterize the cargo of these vesicles; however, no consensus has been reached, challenging the comparison among studies. This results in a vast number of studies portraying an extensive list of uEV-derived candidate biomarkers for urologic cancers, with the potential to improve clinical outcome; however, without significant validation. Herein, we review the current published research on miRNA and protein-derived uEV for prostate, bladder and kidney cancers, focusing on different uEV isolation methods, and its implications for biomarker studies.
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http://dx.doi.org/10.3390/cancers13071529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036842PMC
March 2021

Secreted Extracellular Vesicle Molecular Cargo as a Novel Liquid Biopsy Diagnostics of Central Nervous System Diseases.

Int J Mol Sci 2021 Mar 23;22(6). Epub 2021 Mar 23.

Cancer Biology & Epigenetics Group, Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.

Secreted extracellular vesicles (EVs) are heterogeneous cell-derived membranous granules which carry a large diversity of molecules and participate in intercellular communication by transferring these molecules to target cells by endocytosis. In the last decade, EVs' role in several pathological conditions, from etiology to disease progression or therapy evasion, has been consolidated, including in central nervous system (CNS)-related disorders. For this review, we performed a systematic search of original works published, reporting the presence of molecular components expressed in the CNS via EVs, which have been purified from plasma, serum or cerebrospinal fluid. Our aim is to provide a list of molecular EV components that have been identified from both nonpathological conditions and the most common CNS-related disorders. We discuss the methods used to isolate and enrich EVs from specific CNS-cells and the relevance of its components in each disease context.
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http://dx.doi.org/10.3390/ijms22063267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004928PMC
March 2021