Mayra Paolillo

Mayra Paolillo
University of Pavia | UNIPV · Department of Drugs Sciences

PhD

About

58
Publications
6,840
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,981
Citations
Introduction
Additional affiliations
Position
  • Toxicology

Publications

Publications (58)
Article
Full-text available
Compounds targeting non-canonical secondary structures of nucleic acids, known as G-quadruplexes, are highly cytotoxic, both for cancer and healthy cells, because of their action mechanism’s lack of appropriate selectivity. The targeted delivery of cytotoxic molecules to cancer cells is a valuable strategy to expand the repertoire of potential drug...
Preprint
Full-text available
Compounds targeting non-canonical secondary structures of nucleic acids, known as G-quadruplexes, are highly cytotoxic, both for cancer and healthy cells, because of their action mechanism's lack of appropriate selectivity. The targeted delivery of cytotoxic molecules to cancer cells is a valuable strategy to expand the repertoire of potential drug...
Article
Full-text available
Simple Summary Recent advances in anticancer drug research led to the approval of new small molecules with different mechanisms of action, therapeutic indications, and adverse reactions. In this review, small molecules recently approved for metastatic cancer therapy or in trials belonging to different pharmacological classes are described. Particul...
Preprint
Full-text available
Metastasis is the main cause of anti-cancer therapies failure, leading to unfavorable prognosis for patients. The true challenge to increase cancer patient life expectancy by making cancer a chronic disease with periodic but manageable relapses, relies on the development of efficient therapeutic strategies specifically directed against key targets...
Article
Full-text available
Cell-based bioreactors are important tools for evaluating molecule absorption in dynamic conditions, simulating simil-physiological flow, transport, and biological barriers. They allow for absorption and metabolization studies to be performed, obtaining very predictive data of in vivo conditions. In this paper, a new dynamic model is proposed to ev...
Article
Full-text available
Developing drug delivery systems to target cytotoxic drugs directly into tumor cells is still a compelling need with regard to reducing side effects and improving the efficacy of cancer chemotherapy. In this work, silk fibroin nanoparticles (SFNs) have been designed to load a previously described cytotoxic compound (NDI-1) that disrupts the cell cy...
Article
Full-text available
Salicylaldehyde (SA) derivatives are emerging as useful fragments to obtain reversible‐covalent inhibitors interacting with the lysine residues of the target protein. Here the SA installation at the C terminus of an integrin‐binding cyclopeptide, leading to enhanced ligand affinity for the receptor as well as stronger biological activity in culture...
Article
Full-text available
Chlorogenic acids are hydroxycinnamic derivatives widespread in food or food by-products, known for their antioxidant effects and ability to interfere with the formation of advanced glycation end products (AGEs). AGEs are potential glycotoxins involved in age-related disorders, such as diabetes, cardiovascular diseases, and neurological disorders....
Article
Full-text available
Peptide-decorated nanosystems have demonstrated higher stability and improved cellular uptake as compared to bare NPs and appear highly promising in diagnostics and theranostics of cancer. Herein, we discuss the preparation and structural characterization of peptide-functionalized silica/PEG NPs, starting from peptide–block copolymers, prepared in...
Article
Full-text available
Photodynamic therapy (PDT) has recently attracted interest as an innovative and adjuvant treatment for different cancers including malignant gliomas. Among these, Glioblastoma (GBM) is the most prevalent neoplasm in the central nervous system. Despite conventional therapeutic approaches that include surgical removal, radiation, and chemotherapy, GB...
Article
Full-text available
Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has so far mainly been investigated as a function of EX cargo, while few studies have focused on the...
Article
Full-text available
Simple Summary In this review, the thorny issue of glioblastoma models is addressed, with a focus on 3D in vitro models. In the first part of the manuscript, glioblastoma features and classification are recapitulated, in order to highlight the major critical aspects that should be taken into account when choosing a glioblastoma 3D model. In the sec...
Article
Full-text available
Arg-Gly-Asp (RGD)-based cyclopentapeptides (cRGDs) have a high affinity towards integrin αvβ3 and αvβ5, which are overexpressed by many tumor cells. Here, curcumin-loaded silk fibroin nanoparticles (SFNs) have been functionalized on the surface with cRGD to provide active targeting towards tumor cells; a “click reaction” between the RGD-based cyclo...
Article
Full-text available
Extracellular vesicles (EVs) are considered as promising nanoparticle theranostic tools in many pathological contexts. The increasing clinical employment of therapeutic nanoparticles is contributing to the development of a new research area related to the design of artificial EVs. To this aim, different approaches have been described to develop mim...
Article
Full-text available
Cancer cells demonstrate elevated expression levels of the inhibitor of apoptosis proteins (IAPs), contributing to tumor cell survival, disease progression, chemo-resistance, and poor prognosis. Smac/DIABLO is a mitochondrial protein that promotes apoptosis by neutralizing members of the IAP family. Herein, we describe the preparation and in vitro...
Article
Full-text available
Metastatic spread is mainly sustained by cancer stem cells (CSC), a subpopulation of cancer cells that displays stemness features. CSC are thought to be derived from cancer cells that undergo epithelial to mesenchymal transition (EMT), thus acquiring resistance to anoikis and anti-cancer drugs. After detachment from the primary tumor mass, CSC reac...
Article
Full-text available
The extracellular matrix (ECM) is a complex network of extracellular-secreted macromolecules, such as collagen, enzymes and glycoproteins, whose main functions deal with structural scaffolding and biochemical support of cells and tissues. ECM homeostasis is essential for organ development and functioning under physiological conditions, while its su...
Article
A C2-symmetric bicyclic peptide bearing two RGD motifs was developed as dimeric ligand, and displayed enhanced inhibition of ECM protein binding to purified integrin receptors as compared to monomeric RGD...
Article
The search for new in-vitro modular bioreactors to simulate flow-mediated transport and absorption of chemical substances is a very important issue in toxicology as well as in drug and bioactive delivery research. The possibility to set up a dynamic microenvironment leads to experimental conditions that may more closely resemble the in vivo model,...
Article
Full-text available
Ligand‐based control of protein functional motions can provide novel opportunities in the study of fundamental biological mechanisms and in the development of novel therapeutics. In this work we addressed the ligand‐based modulation of integrin functions. Inhibitors of integrin αvβ3 are interesting anticancer agents but their molecular mechanisms a...
Article
Full-text available
The malignancy of glioblastoma (GB) is primarily due to the ability of glioma cancer stem cells (GSC) to disseminate into surrounding brain tissues, despite surgery and chemotherapy, and to form new tumoral masses. Members of the RGD-binding integrin family, which recognize the arginine-glycine-aspartic acid (RGD) sequence present in components of...
Article
In this manuscript we report on the design, synthesis and evaluation of dual Sigma 1 Receptor (S1R) modulators/Acetylcholinesterase (AChE) inhibitors endowed with antioxidant and neurotrophic properties, potentially able to counteract neurodegeneration. The compounds based on arylalkylaminoketone scaffold integrate the pharmacophoric elements of RR...
Article
Full-text available
Despite the interest aroused by sigma receptors (SRs) in the area of oncology, their role in tumor biology remains enigmatic. The predominant subcellular localization and main site of activity of SRs are the endoplasmic reticulum (ER). Current literature data, including recent findings on the sigma 2 receptor subtype (S2R) identity, suggest that SR...
Article
Full-text available
Glioblastoma is known to be one of the most lethal and untreatable human tumors. Surgery and radiotherapy in combination with classical alkylating agents such as temozolomide offer little hope to escape a poor prognosis. For these reasons, enormous efforts are currently devoted to refine in vivo and in vitro models with the specific goal of finding...
Article
Full-text available
Integrin activity and function is classically related to the bi-directional regulation of cell-extracellular matrix (ECM) contacts that regulate a number of cell pathways linked to cell adhesion, cell detachment from ECM, cell migration, and anoikis. Interestingly, emerging data continue to uncover new roles for integrins in cancer-relevant pathway...
Article
In the early 2000s, the Sigma Receptor (SR) family was identified as potential “druggable” target in cancer treatment. Indeed, high density of SRs was found in breast, lung, and prostate cancer cells, supporting the idea that SRs could play a role in tumor growth and progression. Moreover, a link between the degree of SR expression and tumor aggres...
Article
Full-text available
Brain infiltration by cancer cells is a complex process in which metastatic cells detached from the primary tumor must firstly survive in the blood flow, cross the blood brain barrier (BBB) and finally colonize a foreign microenvironment. The cells that successfully bypass the cellular barriers surrounding capillaries, proliferate to form micrometastas...
Article
The cyclo[DKP-isoDGR] peptidomimetics 2-5, containing bifunctional diketopiperazine (DKP) scaffolds that differ in the configuration of the two DKP stereocenters and in the substitution at the DKP nitrogen atoms, were prepared and examined in vitro in competitive binding assays with purified αv β3 and αv β5 integrin receptors. IC50 values ranged fr...
Article
Full-text available
Background Cyclic RGD peptidomimetics containing a bifunctional diketopiperazine scaffold are a novel class of high-affinity ligands for the integrins αVβ3 and αVβ5. Since integrins are a promising target for the modulation of normal and pathological angiogenesis, the present study aimed at characterizing the ability of the RGD peptidomimetic cyclo...
Article
Full-text available
In cancer cells integrins modulate important cellular events that regulate the metastasic cascade which involves detachment from the tumor mass, dissemination and attachment to the oncogenic niche. The α5β1, αvβ3 and αvβ5 integrins are widely expressed in different cancer types and recognize the tripeptide Arg-Gly-Asp (RGD) motif present in several...
Article
The proliferative and antiapoptotic actions of endothelin (ET)-1 in cancer cells have been documented and ET receptor antagonists have been exploited as potential anticancer drugs. Glioblastoma cell lines express both ETA and ETB receptors and previous works have shown that ETB receptors are involved in the proliferation of different cancer cell ty...
Article
Full-text available
Integrins are a large family of dimeric receptors composed by alpha and beta subunits that, once bound to extra-cellular matrix (ECM) proteins, regulate a variety of cellular processes such as cell motility, migration, and proliferation. The integrins transduce signals from inside-out and outside-in the cell, thus representing the cellular link to...
Article
Full-text available
In this study the mRNA levels of five EGFR indirectly related genes, EGFR, HB-EGF, ADAM17, PTEN, and MMP9, have been assessed by Real-time PCR in a panel of 37 glioblastoma multiforme specimens and in 5 normal brain samples; as a result, in glioblastoma, ADAM17 and PTEN expression was significantly lower than in normal brain samples, and, in partic...
Article
Full-text available
The epidermal growth factor receptor (EGFR) is the main tyrosine kinase receptor dysregulated or overexpressed in brain cancer types and its expression is directly correlated with tumor malignancy and unfavorable prognosis. Recently, the availability of endogenous EGFR ligands has been reported to be also regulated indirectly by the activation of s...
Article
: D1-and D2-dopamine receptors exert important physiological actions on striatal neurons, but the intracellular second messenger pathways activated by these receptors are still incompletely understood. Using primary cultures of rat striatal cells, we have examined the effects of activating D1 or D2 receptors on arachidonic acid (AA) release and cyc...
Article
The endothelins (ETs) are a family of three peptides named ET-1, ET-2 and ET-3 that have been initially isolated as potent vasoactive peptides; ETs are synthesized as precursor proteins (preproETs) and are activated by proteolytic cleavage. ETs exert their biological effects through the activation of two receptors subtypes, ETA and ETB. Recent stud...
Article
Full-text available
The vasoconstrictor peptide endothelin (ET-1) exerts its physiological and pathological effects via activation of ET(A) and ET(B) receptor (ET-R) subtypes. In this study, we demonstrate that both ET-R subtypes are highly expressed in rat astrocytes in vivo, indicating that these cells are potential targets of the biological effects of ET-1 in the b...
Article
Full-text available
Activation of the cAMP-dependent protein kinase A (PKA) pathway may induce cAMP-response element-binding protein (CREB) phosphorylation either directly or via cross-talk mechanisms with other signal transduction pathways. In this study, we have investigated in striatal primary cultures the mechanism by which activation of the cAMP/PKA-dependent pat...
Article
The neurotransmitter dopamine (DA) at a 10 microM concentration elicited a stimulation of intracellular cyclic AMP (cAMP) accumulation in cultured astrocytes derived from embryonic rat striatum. This accumulation was partially blocked by the beta-adrenergic receptors antagonist propranolol, mimicked by the D(1) agonist SKF 38393 and by the mixed D(...
Article
The neurotransmitter dopamine (DA) at a 10 μM concentration elicited a stimulation of intracellular cyclic AMP (cAMP) accumulation in cultured astrocytes derived from embryonic rat striatum. This accumulation was partially blocked by the β-adrenergic receptors antagonist propranolol, mimicked by the D1 agonist SKF 38393 and by the mixed D1/D2 agoni...
Article
cAMP signals are received and transmitted by multiple isoforms of cAMP-dependent protein kinases, typically determined by their specific regulatory subunits. In the brain the major regulatory isoform RIIbeta and the RII-anchor protein, AKAP150 (rat) or 75 (bovine), are differentially expressed. Cortical neurons express RIIbeta and AKAP75; conversel...
Article
Full-text available
cAMP signals are received and transmitted by multiple isoforms of cAMP-dependent protein kinases, typically determined by their specific regulatory subunits. In the brain the major regulatory isoform RIIβ and the RII-anchor protein, AKAP150 (rat) or 75 (bovine), are differentially expressed. Cortical neurons express RIIβ and AKAP75; conversely, gr...
Article
Metabotropic glutamate receptors have been shown to potentiate the cyclic adenosine monophosphate (cAMP) formation induced by activation of several receptors linked to adenylyl cyclase via Gs-protein. Here we show that, in primary cultures of striatal neurons, group I metabotropic receptors potentiate the cAMP formation induced by activation of D1-...
Article
The expression and activity of phospholipase A2 (PLA2) isoforms were investigated in primary cultures of striatal astrocytes. The calcium ionophore A23187 together with the protein kinase C activator phorbol ester was the most potent stimulus in eliciting [3H]arachidonic acid release in the extracellular medium. Reverse transcription coupled to pol...
Article
Fibroblasts from Alzheimer's disease (AD) patients displayed decreased cytochrome c oxidase (complex IV) activity (P<0.05). The basal oxygen consumption rate (QO2) and the response to an uncoupler of oxidative phosphorylation did not differ between AD and control fibroblasts. The QO2 of AD fibroblasts was more susceptible (P<0.05) to inhibition by...
Article
We analyzed the expression and relative distribution of mRNA for the regulatory subunits (RIalpha, RIIalpha, and RIIbeta) and of 150-kDa RIIbeta-anchor proteins for cyclic AMP (cAMP)-dependent protein kinase (PKA) into discrete brain regions. The subcellular distribution of both holoenzyme and free catalytic subunit was evaluated in the same CNS ar...
Article
D1- and D2-dopamine receptors exert important physiological actions on striatal neurons, but the intracellular second messenger pathways activated by these receptors are still incompletely understood. Using primary cultures of rat striatal cells, we have examined the effects of activating D1 or D2 receptors on arachidonic acid (AA) release and cycl...
Article
The modulation of cAMP formation by protein kinase C (PKC), activated by phorbol-12-myristate-13-acetate, and by Ca2+ entry, using the ionophore A23187, was investigated in rat striatal neurons grown in primary dissociated cell culture. Phorbol-12-myristate-13-acetate (PMA) potentiated forskolin-induced and dopamine-induced cAMP formation in a conc...
Article
We have developed an HPLC method using electrochemical detection (ED) to study the synthesis, uptake and metabolism of dopamine (DA) in primary cell cultures dissociated from rat embryonic mesencephalon. The method is rapid and simple and is also able to detect, after 7 days in vitro incubation (DIV), intracellular levels of L-3,4-dihydroxyphenylal...
Article
An HPLC method with electrochemical detection for the simultaneous measurement of serotonin (5-hydroxytryptamine) and 5-hydroxyindoleacetic acid in primary mesencephalic cell culture is described. The serotonin and 5-hydroxyindoleacetic acid cell content was measured on different days of growth in vitro; after twelve days in culture the amounts of...

Network

Cited By