Alessandra Affinito's research while affiliated with University of Naples Federico II and other places

Publications (30)

Article
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Extracellular vesicles (EVs) shuttle proteins, RNA, DNA, and lipids crucial for cell-to-cell communication. Recent findings have highlighted that EVs, by virtue of their cargo, may also contribute to breast cancer (BC) growth and metastatic dissemination. Indeed, EVs are gaining great interest as non-invasive cancer biomarkers. However, little is k...
Article
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Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. TNBC progression is sustained by the recruitment of a strong tumor microenvironment (TME) mainly composed of Cancer-Associated Fibroblasts (CAFs) able to endorse tumor hallmarks. Increasing evidence demonstrated that exosomes mediate the crosstalk between cancer cell...
Article
Background Administration of iodinated contrast medium (CM) during invasive cardiovascular procedures may be associated with impairment of kidney function. Objectives Urinary dickkopf-3 (DKK3), a stress-induced renal tubular epithelium–derived glycoprotein, has been identified as a biomarker predicting both acute kidney injury (AKI) and persistent...
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Lung cancer is still the leading cause of death by cancer worldwide despite advances both in its detection and therapy. Multiple oncogenic driver alterations have been discovered, opening the prospective for new potential therapeutic targets. Among them, KRAS mutations represent the most frequent oncogene aberrations in non-small cell lung cancer (...
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Glioblastoma (GBM) is the most lethal primary brain tumor of the central nervous system in adults. Despite advances in surgical and medical neuro-oncology, the median survival is about 15 months. For this reason, initial diagnosis, prognosis, and targeted therapy of GBM represent very attractive areas of study. Aptamers are short three-dimensional...
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Background: Targeted image-guided surgery is based on the detection of tumor cells after administration of a radio-active or fluorescent tracer. Hence, enhanced binding of a tracer to tumor tissue compared to healthy tissue is crucial. Various tumor antigens have been evaluated as possible targets for image-guided surgery of breast cancer, with mi...
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Breast cancer is the most frequent malignancy in females in terms of both incidence and mortality. Underlying the high mortality rate is the presence of cancer stem cells, which divide indefinitely and are resistant to conventional chemotherapies, so causing tumor relapse. In the present study, we identify miR-216a-5p as a downregulated microRNA in...
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Despite the benefit associated with radiotherapy and chemotherapy for glioblastoma treatment, the majority of the patients experience a relapse following initial therapy. Recurrent or pregressive GBM usually do not responde anymore to standard therapy and this is associated to poor patient outcome. Glioblastoma stem cells (GSCs) are a subset of cel...
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Due to the progress made in the area of precision and personalized medicine in the field of cancer therapy, strategies to selectively and specifically identify target molecules causative of the diseases are urgently needed. Efforts are being made by a number of different laboratories, companies, and researchers to develop therapeutic molecules that...
Article
Background Increasing evidence indicates that the release of exosomes by tumor cells play a key role in tumor progression, drug resistance, immune surveillance escape, angiogenesis, tumor invasion, and metastasis. For this reason, cancer-derived exosomes are emerging as very interesting targets for early diagnosis and therapy in cancer, including b...
Article
Background One limitation in the breast cancer research field is that there are few in vitro models of breast cancer able to predict drug response and thus clinical patients’ outcome, mainly because the present models do not take account of the tumor heterogeneity. To address this issue, we developed an in vitro 3D organoid culture system using pri...
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Background Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. Despite progress in surgical and medical neuro-oncology, prognosis for GBM patients remains dismal. It has been demonstrated that the modest benefit of conventional therapies is due to the presence of glioblastoma stem cells (GSCs) that cause tumor relapse and chemo...
Article
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Exosomes are extracellular vesicles released into biological fluids where they act as carriers of various molecules, including proteins, lipids, and RNAs, between cells, modulating or perturbing specific physiological processes. Recently, it has been suggested that tumoral cells release excessive amounts of exosomes that, through their cargo, promo...
Article
Full-text available
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. Despite progress in surgical and medical neuro-oncology, prognosis for GBM patients remains dismal, with a median survival of only 14-15 months. The modest benefit of conventional therapies is due to the presence of GBM stem cells (GSCs) that cause tumor relapse and chemoresis...
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MicroRNAs (miRNAs) are key regulators of different human processes that represent a new promising class of cancer therapeutics or therapeutic targets. Indeed, in several tumor types, including non-small-cell lung carcinoma (NSCLC), the deregulated expression of specific miRNAs has been implicated in cell malignancy. As expression levels of the onco...
Article
Breast cancer is one of the leading causes of cancer mortality among women. The main causes of death are related to recurrence and metastasis. One major limitation in the breast cancer research field is that there are few in vitro models of breast cancer able to predict clinical patients' outcome. The main reason of this failure is that the present...
Article
Glioblastoma (GBM) is the most frequent and aggressive primary brain tumour in adults. Despite advances in surgical and medical neuro oncology, prognosis for GBM patients remains dismal, with a median survival of about 15 months. It has been demonstrated that the modest benefit of conventional therapies depends on a small population of cancer stem...
Data
Data from intracellular calcium analysis in HL-1 treated cells. (XLSX)
Article
Full-text available
Small therapeutic peptides represent a promising field for the treatment of pathologies such as cardiac diseases. However, the lack of proper target-selective carriers hampers their translation towards a potential clinical application. Aptamers are cell-specific carriers that bind with high affinity to their specific target. However, some limitatio...
Article
Cancer-associated fibroblasts (CAFs), the major components of the tumor microenvironment may drive tumor progression. Exosomes mediate horizontal transfer of miRs, mRNAs and proteins, thus affecting breast cancer progression. Differential expression profile analysis identified three miRs increased in exosomes from CAFs as compared from normal fibro...
Article
Full-text available
Cancer-associated fibroblasts (CAFs) are the major components of the tumor microenvironment. They may drive tumor progression, although the mechanisms involved are still poorly understood. Exosomes have emerged as important mediators of intercellular communication in cancer. They mediate horizontal transfer of microRNAs (miRs), mRNAs and proteins,...
Article
Full-text available
Glioblastoma multiforme (GBM) is characterized by a strong self-renewal potential and a poor differentiation state. Since receptor-like tyrosine kinase (RYK) activates the WNT/β-catenin pathway essential for cancer stem cell maintenance, we evaluated its contribution in conferring stemness to GBM cells. Here, we report that Ryk (related-to-receptor...
Article
Full-text available
Breast cancer remains one of the leading causes of cancer mortality among women. It has been proved that the onset of cancer depends on a very small pool of tumor cells with a phenotype similar to that of normal adult stem cells. Cancer stem cells (CSC) possess self-renewal and multilineage differentiation potential as well as a robust ability to s...
Article
Full-text available
Glioblastoma is the most common primary brain tumor in adults; with a survival rate of 12 months from diagnosis. However, a small subgroup of patients, termed long-term survivors (LTS), has a survival rate longer then 12-14 months. There is thus increasing interest in the identification of molecular signatures predicting glioblastoma prognosis and...

Citations

... Other studies used proteomic approach by 2DE to perform EVs profiling, such as Di Giuseppe et al. in the characterization of two different EVs subpopulations isolated from human glioblastoma stem cell secretome [57], as well as Kitamura et al., who performed a proteomic profiling of exosomes from blood samples of patients affected by Parkinson's disease [58]. Of equal importance, mass spectrometry by shotgun approach might provide a wide and highly sensitive range of information on EVs proteomic content, contributing considerably to their characterization and profiling [59][60][61][62][63]. Furthermore, this high-throughput approach has been continuously demonstrating its potentiality in EVs biomarkers discovery, as well as their therapeutical applications [64,65]. ...
... The present study paves the way for increasing analysis complexity, querying, and the combination of results from multiple search engines, a most powerful approach [10,33,34], to generate a highly confident proteome set for individual samples. EV biogenesis, isolation, and proteomics from patient-derived and continuous cell lines is still a poorly explored world that could lead to a plethora of therapeutic and diagnostic applications [5,37,38]. Our analysis pipeline has shed light on a common signature of 49 proteins in EVs from primary and model BC cells: the two proteins that were studied for experimental validation (COL1A2 and KRT2) agreed with the in-silico findings. ...
... Although sustained activation of Wnt-β-catenin signaling is considered detrimental and promotes tubulointerstitial fibrosis, transient activation is thought to mitigate initial injury and accelerate subsequent recovery after AKI [93,94]. Therefore, persistently elevated urinary dickkopf-3 levels may indicate ongoing tubular "stress" leading to progressive kidney fibrosis in various-cause CKD [95,96]. Currently, urinary dickkopf-3 is the only biomarker that has been validated for AKI risk assessment before exposure to kidney injury [32]. ...
... [19][20][21] For example, the tumor suppressor miR-34 family is recognized as one of the most significant in cancer and is investigated in numerous pre-clinical and clinical studies. [22][23][24][25][26][27][28][29] A miR-34a mimic-based drug was employed in the MRX34 clinical trial (NCT01829971), which was the first-in-human phase 1 study of miRNA-based cancer therapy. 30 Even though the clinical trial terminated prematurely, it was the first concrete application of miRNAs in the clinic and a solid proof of concept for miRNA-based cancer therapy. ...
... Aptamers are oligonucleotides (ssDNA or RNA) that are selected to recognize a molecular target with high affinity and specificity. Several aptamers have been developed for biomedical applications, including molecular imaging, diagnostics, therapies, drug administration, and clinical procedures [9][10][11][12]. The Food and Drug Administration (FDA) has approved aptamers as therapeutic agents, with several clinical trials currently underway [9][10][11][12]. ...
... It also has been shown to have an antitumor effect in various human tumors. For instance, Roscigno G et al. reported that miR-216a acts as a suppressor to reduce stem-like properties and influence the interaction between cells and the microenvironment in breast cancer (35 (37). Wang W et al. found that miR-216a suppressed glioma cell progression and promoted apoptosis through the miR-216a/LGR5 axis (38). ...
... Considering the significance of GSCs in GB recurrence and treatment resistance, these aptamers provide novel drug delivery options with significant possibilities in the management of GB. Another study by Affinito et al. [85] investigated the biological roles of the 2 ′ -fluoropyrimidine-containing RNA aptamer 40 L and its shortened version A40s. They found these aptamers as a high-affinity ligand for EphA2, upregulated by a subpopulation of GSCs cultured as tumorspheres [85]. ...
... Conjugation of nanobodies, antibody fragments that recognize specific antigens, have been explored and enable the delivery of functional siRNAs via EGFR receptors [36]. Similarly, aptamers, which can also be viewed as chemical antibodies (along with being simpler and less expensive to manufacture) can target specific proteins and efficiently deliver siRNA to specific cell types [86]. Similar to antibodies, centyrin conjugates -small, engineered proteins derived from a human protein Tenascin C -have been designed to bind with high affinity and selectivity to numerous antigens, which makes specific tumour targeting across a broad range of tumour antigens feasible. ...
... The methods used to identify and target GSCs have not been completely successfully, as the exact mechanisms and functionalities of the putative GSCs markers have not yet been fully elucidated. RNA aptamers that selectively bind to GSCs were previously created on human primary GSCs using cell-systematic evolution of ligand by exponential enrichment methodology (SELEX) (179). Using a cell-SELEX approach, RNA aptamers that selectively bind GSCs were generated. ...
... These extracellular vesicles (EV) can fuse with the membrane of target cells and deliver exosome surface proteins, carbohydrates, lipids, and nucleic acids. They are non-immunogenic and non-oncogenic, present negligible toxicity, and thus stand as a promising and innovative platform for miRNA delivery [73]. Shtam et al. have shown that exosomes can efficiently deliver siRNA into target cancer cells, leading to gene silencing and cancer cell death [74]. ...