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Article ; Online: Pancreatic Cancer Biomarkers: Oncogenic Mutations, Tissue and Liquid Biopsies, and Radiomics-A Review.

Amaral, Maria João / Oliveira, Rui Caetano / Donato, Paulo / Tralhão, José Guilherme

2023 Volume 68, Issue 7, Page(s) 2811–2823

Abstract: Pancreatic cancer is one of the most fatal malignancies, as approximately 80% of patients are at advanced stages by the time of diagnosis. The main reason for the poor overall survival is late diagnosis that is partially due to the lack of tools for ... ...

Abstract	Pancreatic cancer is one of the most fatal malignancies, as approximately 80% of patients are at advanced stages by the time of diagnosis. The main reason for the poor overall survival is late diagnosis that is partially due to the lack of tools for early-stage detection. In addition, there are several challenges in evaluating response to treatment and predicting prognosis. In this article, we do a review of the most common pancreatic cancer biomarkers with emphasis in new and promising approaches. Liquid biopsies seem to have important clinical applications in early detection, screening, prognosis, and longitudinal monitoring of on-treatment patients. Together with biomarkers in imaging, can represent valuable alternative non-invasive tools in order to achieve a more effective management of pancreatic cancer patients.
MeSH term(s)	Humans ; Biomarkers, Tumor/genetics ; Pancreatic Neoplasms/diagnostic imaging ; Pancreatic Neoplasms/genetics ; Liquid Biopsy/methods ; Mutation ; Pancreatic Neoplasms
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2023-03-29
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	304250-9
ISSN	1573-2568 ; 0163-2116
ISSN (online)	1573-2568
ISSN	0163-2116
DOI	10.1007/s10620-023-07904-6
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Article ; Online: Intrinsic disorder and phase transitions: Pieces in the puzzling role of the prion protein in health and disease.

do Amaral, Mariana J / Cordeiro, Yraima

Progress in molecular biology and translational science

2021 Volume 183, Page(s) 1–43

Abstract: After four decades of prion protein research, the pressing questions in the literature remain similar to the common existential dilemmas. Who am I? Some structural characteristics of the cellular prion protein ( ... ...

Abstract	After four decades of prion protein research, the pressing questions in the literature remain similar to the common existential dilemmas. Who am I? Some structural characteristics of the cellular prion protein (PrP
MeSH term(s)	Animals ; Humans ; Intrinsically Disordered Proteins ; PrPSc Proteins ; Prion Diseases ; Prion Proteins/chemistry ; Prion Proteins/genetics ; Prion Proteins/metabolism ; Prions
Chemical Substances	Intrinsically Disordered Proteins ; PRNP protein, human ; PrPSc Proteins ; Prion Proteins ; Prions
Language	English
Publishing date	2021-08-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2471995-X
ISSN	1878-0814 ; 0079-6603 ; 1877-1173
ISSN (online)	1878-0814
ISSN	0079-6603 ; 1877-1173
DOI	10.1016/bs.pmbts.2021.06.001
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Article: (Dys)functional insights into nucleic acids and RNA-binding proteins modulation of the prion protein and α-synuclein phase separation.

Cordeiro, Yraima / Freire, Maria Heloisa O / Wiecikowski, Adalgisa Felippe / do Amaral, Mariana Juliani

Biophysical reviews

2023 Volume 15, Issue 4, Page(s) 577–589

Abstract: Prion diseases are prototype of infectious diseases transmitted by a protein, the prion protein (PrP), and are still not understandable at the molecular level. Heterogenous species of aggregated PrP can be generated from its monomer. α-synuclein (αSyn), ... ...

Abstract	Prion diseases are prototype of infectious diseases transmitted by a protein, the prion protein (PrP), and are still not understandable at the molecular level. Heterogenous species of aggregated PrP can be generated from its monomer. α-synuclein (αSyn), related to Parkinson's disease, has also shown a prion-like pathogenic character, and likewise PrP interacts with nucleic acids (NAs), which in turn modulate their aggregation. Recently, our group and others have characterized that NAs and/or RNA-binding proteins (RBPs) modulate recombinant PrP and/or αSyn condensates formation, and uncontrolled condensation might precede pathological aggregation. Tackling abnormal phase separation of neurodegenerative disease-related proteins has been proposed as a promising therapeutic target. Therefore, understanding the mechanism by which polyanions, like NAs, modulate phase transitions intracellularly, is key to assess their role on toxicity promotion and neuronal death. Herein we discuss data on the nucleic acids binding properties and phase separation ability of PrP and αSyn with a special focus on their modulation by NAs and RBPs. Furthermore, we provide insights into condensation of PrP and/or αSyn in the light of non-trivial subcellular locations such as the nuclear and cytosolic environments.
Language	English
Publishing date	2023-06-06
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2486483-3
ISSN	1867-2469 ; 1867-2450
ISSN (online)	1867-2469
ISSN	1867-2450
DOI	10.1007/s12551-023-01067-4
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Article ; Online: Extensive thrombosis after COVID-19 vaccine: cause or coincidence?

Graça, Luís Lourenço / Amaral, Maria João / Serôdio, Marco / Costa, Beatriz

BMJ case reports

2021 Volume 14, Issue 8

Abstract: A 62-year-old Caucasian female patient presented with abdominal pain, vomiting and fever 1 day after administration of COVID-19 vaccine. Bloodwork revealed anaemia and thrombocytosis. Abdominal CT angiography showed a mural thrombus at the emergence of ... ...

Abstract	A 62-year-old Caucasian female patient presented with abdominal pain, vomiting and fever 1 day after administration of COVID-19 vaccine. Bloodwork revealed anaemia and thrombocytosis. Abdominal CT angiography showed a mural thrombus at the emergence of the coeliac trunk, hepatic and splenic arteries, and extensive thrombosis of the superior and inferior mesenteric veins, splenic and portal veins, and the inferior vena cava, extending to the left common iliac vein. The spleen displayed extensive areas of infarction. Aetiological investigation included assessment of congenital coagulation disorders and acquired causes with no relevant findings. Administration of COVID-19 vaccine was considered a possible cause of the extensive multifocal thrombosis. After reviewing relevant literature, it was considered that other causes of this event should be further investigated. Thrombosis associated with COVID-19 vaccine is rare and an aetiological relationship should only be considered in the appropriate context and after investigation of other, more frequent, causes.
MeSH term(s)	COVID-19 ; COVID-19 Vaccines ; Female ; Humans ; Middle Aged ; SARS-CoV-2 ; Thrombosis/etiology ; Vena Cava, Inferior/diagnostic imaging
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2021-08-16
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2021-244878
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Article ; Online: In Vitro Characterization of Protein:Nucleic Acid Liquid-Liquid Phase Separation by Microscopy Methods and Nanoparticle Tracking Analysis.

do Amaral, Mariana J / Passos, Yulli M / Almeida, Marcius S / Pinheiro, Anderson S / Cordeiro, Yraima

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2551, Page(s) 605–631

Abstract: Uncontrolled assembly/disassembly of physiologically formed liquid condensates is linked to irreversible aggregation. Hence, the quest for understanding protein-misfolding disease mechanism might lie in the studies of protein:nucleic acid coacervation. ... ...

Abstract	Uncontrolled assembly/disassembly of physiologically formed liquid condensates is linked to irreversible aggregation. Hence, the quest for understanding protein-misfolding disease mechanism might lie in the studies of protein:nucleic acid coacervation. Several proteins with intrinsically disordered regions as well as nucleic acids undergo phase separation in the cellular context, and this process is key to physiological signaling and is related to pathologies. Phase separation is reproducible in vitro by mixing the target recombinant protein with specific nucleic acids at various stoichiometric ratios and then examined by microscopy and nanotracking methods presented herein. We describe protocols to qualitatively assess hallmarks of protein-rich condensates, characterize their structure using intrinsic and extrinsic dyes, quantify them, and analyze their morphology over time. Analysis by nanoparticle tracking provides information on the concentration and diameter of high-order protein oligomers formed in the presence of nucleic acid. Using the model protein (globular domain of recombinant murine PrP) and DNA aptamers (high-affinity oligonucleotides with 25 nucleotides in length), we provide examples of a systematic screening of liquid-liquid phase separation in vitro.
MeSH term(s)	Mice ; Animals ; Nucleic Acids ; Microscopy ; Aptamers, Nucleotide ; Recombinant Proteins ; Nanoparticles ; Intrinsically Disordered Proteins/chemistry
Chemical Substances	Nucleic Acids ; Aptamers, Nucleotide ; Recombinant Proteins ; Intrinsically Disordered Proteins
Language	English
Publishing date	2022-10-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2597-2_37
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Article ; Online: Phase separation of the mammalian prion protein: Physiological and pathological perspectives.

do Amaral, Mariana J / Freire, Maria Heloisa O / Almeida, Marcius S / Pinheiro, Anderson S / Cordeiro, Yraima

Journal of neurochemistry

2022 Volume 166, Issue 1, Page(s) 58–75

Abstract: Abnormal phase transitions have been implicated in the occurrence of proteinopathies. Disordered proteins with nucleic acidbinding ability drive the formation of reversible micron-sized condensates capable of controlling nucleic acid processing/transport. ...

Abstract	Abnormal phase transitions have been implicated in the occurrence of proteinopathies. Disordered proteins with nucleic acidbinding ability drive the formation of reversible micron-sized condensates capable of controlling nucleic acid processing/transport. This mechanism, achieved via liquid-liquid phase separation (LLPS), underlies the formation of long-studied membraneless organelles (e.g., nucleolus) and various transient condensates formed by driver proteins. The prion protein (PrP) is not a classical nucleic acid-binding protein. However, it binds nucleic acids with high affinity, undergoes nucleocytoplasmic shuttling, contains a long intrinsically disordered region rich in glycines and evenly spaced aromatic residues, among other biochemical/biophysical properties of bona fide drivers of phase transitions. Because of this, our group and others have characterized LLPS of recombinant PrP. In vitro phase separation of PrP is modulated by nucleic acid aptamers, and depending on the aptamer conformation, the liquid droplets evolve to solid-like species. Herein, we discuss recent studies and previous evidence supporting PrP phase transitions. We focus on the central role of LLPS related to PrP physiology and pathology, with a special emphasis on the interaction of PrP with different ligands, such as proteins and nucleic acids, which can play a role in prion disease pathogenesis. Finally, we comment on therapeutic strategies directed at the non-functional phase separation that could potentially tackle prion diseases or other protein misfolding disorders.
MeSH term(s)	Animals ; Prion Proteins/metabolism ; Prions/metabolism ; Prion Diseases ; Mammals/metabolism ; Nucleic Acids/metabolism
Chemical Substances	Prion Proteins ; Prions ; Nucleic Acids
Language	English
Publishing date	2022-03-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/jnc.15586
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Article: Clinical Impact of Preoperative Biliary Drainage in Patients with Ductal Adenocarcinoma of the Pancreatic Head.

Amaral, Maria João / Freitas, João / Amaral, Mariana / Serôdio, Marco / Oliveira, Rui Caetano / Donato, Paulo / Tralhão, José Guilherme

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 7

Abstract: Our aim was to study the association between preoperative biliary drainage (PBD) and morbidity following cephalic pancreaticoduodenectomy (CPD) for pancreatic ductal adenocarcinoma (PDAC) and its prognostic impact, which is still controversial in the ... ...

Abstract	Our aim was to study the association between preoperative biliary drainage (PBD) and morbidity following cephalic pancreaticoduodenectomy (CPD) for pancreatic ductal adenocarcinoma (PDAC) and its prognostic impact, which is still controversial in the literature. A retrospective study was conducted, which included 128 patients who underwent CPD for PDAC, divided into two groups: those who underwent PBD (group 1) and those who did not undergo this procedure (group 2). Group 1 was subdivided according to the drainage route: endoscopic retrograde cholangiopancreatography (ERCP), group 1.1, and percutaneous transhepatic cholangiography (PTC), group 1.2. 34.4% of patients underwent PBD, and 47.7% developed PBD-related complications, with 37% in group 1.1 and 64.7% in group 1.2 (
Language	English
Publishing date	2023-03-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13071281
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Article: Tumor Stroma Area and Other Prognostic Factors in Pancreatic Ductal Adenocarcinoma Patients Submitted to Surgery.

Amaral, Maria João / Amaral, Mariana / Freitas, João / Oliveira, Rui Caetano / Serôdio, Marco / Cipriano, Maria Augusta / Tralhão, José Guilherme

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 4

Abstract: Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma, responsible for up to 80% of its volume. The amount of stroma can be associated with prognosis, although there are discrepancies regarding its concrete impact. The aim of this work was to study ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma, responsible for up to 80% of its volume. The amount of stroma can be associated with prognosis, although there are discrepancies regarding its concrete impact. The aim of this work was to study prognostic factors for PDAC patients submitted to surgery, including the prognostic impact of the tumor stroma area (TSA). A retrospective study with PDAC patients submitted for surgical resection was conducted. The TSA was calculated using QuPath-0.2.3 software. Arterial hypertension, diabetes mellitus, and surgical complications Clavien-Dindo>IIIa are independent risk factors for mortality in PDAC patients submitted to surgery. Regarding TSA, using >1.9 × 10
Language	English
Publishing date	2023-02-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13040655
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Article ; Online: Pancreatic microcystic serous cystadenoma: a lethal disease? Rare case of a life-threatening haemorrhage.

Amaral, Maria João / Serôdio, Marco / Ramalhosa, Fátima / Tralhão, José Guilherme

BMJ case reports

2020 Volume 13, Issue 3

Abstract: Serous pancreatic cystadenomas are benign tumours and most cases are detected incidentally. Complications are unusual. A patient with a history of a large pancreatic serous cystadenoma (SCA) presented to the emergency department with abdominal pain and ... ...

Abstract	Serous pancreatic cystadenomas are benign tumours and most cases are detected incidentally. Complications are unusual. A patient with a history of a large pancreatic serous cystadenoma (SCA) presented to the emergency department with abdominal pain and haemodynamic shock. After haemodynamic stabilisation, an urgent abdominal CT scan revealed a large hemoperitoneum but the origin of the bleeding was not found. The patient was submitted to an angiography that revealed a bleeding hypervascular pancreatic mass and an embolisation was done successfully. After 3 weeks, the patient underwent a laparotomic left pancreatectomy with en bloc splenectomy. The anatomopathological results were consistent with a microcystic SCA of the pancreas. Despite the high vascularity of pancreatic SCA, haemorrhage is a very rare but life-threatening complication.
MeSH term(s)	Abdomen, Acute/etiology ; Aged ; Cystadenoma, Serous/complications ; Cystadenoma, Serous/pathology ; Cystadenoma, Serous/surgery ; Female ; Gastrointestinal Hemorrhage/diagnosis ; Gastrointestinal Hemorrhage/etiology ; Hemoperitoneum/diagnostic imaging ; Hemoperitoneum/pathology ; Humans ; Pancreatectomy ; Pancreatic Neoplasms/complications ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/surgery ; Splenectomy
Language	English
Publishing date	2020-03-19
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2019-233562
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Article: Clinicopathological prognostic factors for gallbladder carcinoma: a retrospective study.

Ramalhosa, Fátima / Amaral, Maria João / Serôdio, Marco / Oliveira, Rui Caetano / Teixeira, Paulo / Cipriano, Maria Augusta / Tralhão, José Guilherme

Journal of gastrointestinal oncology

2022 Volume 13, Issue 4, Page(s) 1997–2006

Abstract: Background: Gallbladder carcinoma (GBC) is an uncommon neoplasm with poor long-term survival. Worldwide the incidence rates vary according to geographic area. The multifactorial aetiology and the rarity of the disease limits the studies to improve ... ...

Abstract	Background: Gallbladder carcinoma (GBC) is an uncommon neoplasm with poor long-term survival. Worldwide the incidence rates vary according to geographic area. The multifactorial aetiology and the rarity of the disease limits the studies to improve outcomes in patients, since the treatment remains mostly surgical. The aim of this study was to identify clinicopathological prognostic factors for survival in patients with GBC submitted to surgery in our institution-a tertiary centre in Portugal. Also, to assess the expression of possible biomarkers (HER2, CD44 and ALDH1) in GBC, as well as the frequency of microsatellite instability (MSI) tumours. Methods: Clinicopathological characteristics of 41 consecutive patients that underwent surgical resection for GBC (2008-2019) at our hospital were retrospectively reviewed. Clinicopathological factors were assessed and an immunohistochemical (IHC) analysis was done. Microsatellite stability (MSS) was considered if there was maintenance of nuclear expression of MLH1, MSH2, MSH6 and PMS2. Human epidermal growth factor receptor 2 (HER2) expression was evaluated according to the rules applied for gastric cancer and expression of CD44 and ALH1 was evaluated in order to detect cancer stem cells (CSC). Survival analysis was conducted using Kaplan-Meier and Cox regression was used to find prognostic factors. Results: Incidence of GBC in our cohort of patients was 0.45%, most commonly affecting females. Median overall survival (OS) was 23 months with a 39.6% 5-year survival rate. Stage > II [hazard ratios (HR) =8.58; P=0.007], lymphovascular invasion (LVI) (HR =4.06; P=0.045) and hepatic resection (HR =0.288; P=0.034) independently influenced survival. HER2 positivity and high expression of CD44 or ADLH1 did not show significant influence in survival (P=0.649, P=0.868 and P=0.914, respectively), although HER2 and ALDH1 positive patients showed a tendency to a shorter OS, compared to negative patients. We found no relation between these biomarkers expression and disease stage. All analysed samples had MSS. Conclusions: GBC patients with a worse prognosis can be identified. The overexpression of HER2 could select patients for targeted therapy and prompt tissue sampling in unresectable patients.
Language	English
Publishing date	2022-09-02
Publishing country	China
Document type	Journal Article
ZDB-ID	2594644-4
ISSN	2219-679X ; 2078-6891
ISSN (online)	2219-679X
ISSN	2078-6891
DOI	10.21037/jgo-22-61
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