Silvia Valtorta

Silvia Valtorta
Università degli Studi di Milano-Bicocca | UNIMIB · Department of Surgery and Interdisciplinary Medicine

PhD

About

59
Publications
4,770
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612
Citations
Introduction
Silvia Valtorta currently works at the Department of Medicine and Surgery, Università degli Studi di Milano-Bicocca. Silvia does research in cancer research and imaging. Her projects are on evaluation of cancer response to therapies using PET imaging.
Additional affiliations
February 2022 - present
Italian National Research Council
Position
  • Researcher
April 2012 - March 2016
Italian National Research Council
Position
  • Research fixed time

Publications

Publications (59)
Article
Full-text available
Glioblastoma is the most common and aggressive brain tumor, associated with poor prognosis and survival, representing a challenging medical issue for neurooncologists. Dysregulation of histone-modifying enzymes (HDACs) is commonly identified in many tumors and has been linked to cancer proliferation, changes in metabolism, and drug resistance. Thes...
Article
Full-text available
Background: Glioblastoma is the most aggressive primary brain malignancy in adults, with a poor prognosis of about 14 months. Recent evidence ascribed to metformin (MET), an antihyperglycemic drug, the potential to reduce cancer incidence and progression, but the molecular mechanisms underlying these effects need to be better investigated. Method...
Article
Full-text available
Glioblastoma is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. Glioblastoma shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angioge...
Preprint
Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenes...
Article
Glutamine (Gln) addiction has been recently described as a typical metabolic feature of MM by our group. In order to sustain high Gln demand, MM cells upregulate the expression of the Gln transporters ASCT2, SNAT1 and LAT1 and are characterized by fast Gln uptake. Currently, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is the standard tracer for the...
Article
Full-text available
The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [18F]FDG-PET has some limitations and there is a portion of MM patients who a...
Article
Background The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, FDG-PET has some limitations, since there is a portion of MM patients who are negative, and new tracers are...
Article
Background Understanding the molecular mechanisms of metastatic dissemination, the leading cause of death in cancer patients, is required to develop novel, effective therapies. Extravasation, an essential rate-limiting process in the metastatic cascade, includes three tightly coordinated steps: cancer cell adhesion to the endothelium, trans-endothe...
Article
Full-text available
Glioblastoma (GBM) is a highly aggressive tumor of the brain. Despite the efforts, response to current therapies is poor and 2-years survival rate ranging from 6-12%. Here, we evaluated the preclinical efficacy of Metformin (MET) as add-on therapy to Temozolomide (TMZ) and the ability of [18F]FLT (activity of thymidine kinase 1 related to cell prol...
Article
Rationale: The heterogeneous nature of gliomas makes the development and application of novel treatments challenging. In particular, infiltrating myeloid cells play a role in tumor progression and therapy resistance. Hence, a detailed understanding of the dynamic interplay of tumor cells and immune cells in vivo is necessary. To investigate the com...
Article
Full-text available
Background: Rewiring of metabolism induced by oncogenic K-Ras in cancer cells involves both glucose and glutamine utilization sustaining enhanced, unrestricted growth. The development of effective anti-cancer treatments targeting metabolism may be facilitated by the identification and rational combinatorial targeting of metabolic pathways. Method...
Article
Full-text available
This review highlights the importance and the complexity of tumour biology and microenvironment in the progression and therapy resistance of glioma. Specific gene mutations, the possible functions of several non-coding microRNAs and the intra-tumour and inter-tumour heterogeneity of cell types contribute to limit the efficacy of the actual therapeu...
Article
Full-text available
Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the appearance of α-synuclein insoluble aggregates known as Lewy bodies. Neurodegeneration is accompanied by neuroinflammation mediated by cytokines and chemokines produced by the activated microglia. Several studies demons...
Article
High glycolitic activity of multiple myeloma (MM) cells is the rationale for the use of Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) to detect both medullary and extramedullary disease. However, FDG-PET has some limitations, since there is a good portion of MM patients who are false-negative. Besides enhanced glycolysis...
Article
Full-text available
Hypoxia is a key driver of tumor adaptation promoting tumor progression and resistance to therapy. Hypoxia related pathways might represent attractive targets for the treatment of Glioblastoma Multiforme (GBM), that up to date is characterized by a poor prognosis. Primary aim of this study was to investigate the role of hypoxia and hypoxia-related...
Article
A preclinical insert for small animal simultaneous SPECT and MR imaging, in particular for imaging mouse brains, is presented. It consists of ten static magnetic resonance imaging (MRI)-compatible gamma cameras based on tiles of silicon photomultipliers readout by a multichannel ASIC and coupled to 5 cm $\boldsymbol \times $ 5 cm CsI(Tl) scintill...
Article
Full-text available
Rationale Pathological response to neo-adjuvant chemotherapy (NAC) represents a commonly used predictor of survival in triple negative breast cancer (TNBC) and the need to identify markers that predict response to NAC is constantly increasing. Aim of this study was to evaluate the potential usefulness of PET imaging with [¹⁸F]FDG and [¹⁸F]FLT for t...
Data
[18F]FDG and [18F]FLT SUVmax. [18F]FDG and [18F]FLT SUVmax calculated at the baseline (pre) and post treatment (post) in vehicle and treated mice categorized on the basis of TVR. Multiple comparison assessed using 2-way ANOVA analysis and *p < 0.05, **p < 0.01 and ***p < 0.001. (TIF)
Data
Variation of [18F]FDG and [18F]FLT uptake. [18F]FDG and [18F]FLT uptake expressed as percent variation (% change) in A) TLG (Total Lesion Glycolysis) or TLP (Total lesion Proliferation) and B) MTV (Metabolic Tumor Volume) between baseline and post-therapy in vehicle and treated mice categorized on the basis of TVR. (TIF)
Data
ARRIVE guidelines checklist. (DOCX)
Article
Full-text available
Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression. However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment. Here we report the preclinical evaluation...
Article
Full-text available
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor survival. Cytoreduction in association with radiotherapy and temozolomide (TMZ) is the standard therapy, but response is heterogeneous and life expectancy is limited. The combined use of chemotherapeutic agents with drugs targeting cell metabolism is becoming an inte...
Article
Background: Cardiac arrest is an important cause of morbidity and mortality. Brain injury severity and prognosis of cardiac arrest patients are related to the cerebral areas affected. To this aim, we evaluated the variability and the distribution of brain glucose metabolism after cardiac arrest and resuscitation in an adult rat model. Methods: T...
Article
PurposeIn tumour, the imbalance between oxygen supply and demand leads to hypoxia, which represents a negative prognostic factor associated with aggressive tumour phenotype and therapy resistance. This review provides an overview of the use of positron emitter-labelled radiopharmaceutical used to image hypoxia in preclinical models of cancer. Metho...
Article
Full-text available
NGR (asparagine–glycine–arginine) is a tumor vasculature-homing peptide motif widely used for the functionalization of drugs, nanomaterials, and imaging compounds for cancer treatment and diagnosis. Unfortunately, this motif has a strong propensity to undergo rapid deamidation. This reaction, which converts NGR into isoDGR, is associated with recep...
Article
INTRODUCTION: Gliomas represent the most common adult neoplasm of the primary central nervous system (CNS) characterized by wide necrotic areas, high invasiveness, resistance to therapy and poor prognosis. Glioma is indeed refractory to conventional treatment combining surgery, radiotherapy and chemiotherapy (mostly Temozolomide, TMZ). Hypoxia is c...
Article
Purpose: Lung cancer heterogeneity makes response to therapy extremely hard to predict. Patient-derived xenografts (PDXs) represent a reliable preclinical model that closely recapitulates the main characteristics of the primary tumor and could represent a useful asset to test new therapies. Here, using PET imaging, we verify how lung cancer PDXs r...
Article
Abstract BACKGROUND: Cardiac arrest is an important cause of morbidity and mortality. Brain injury severity and prognosis of cardiac arrest patients are related to the cerebral areas affected. To this aim, we evaluated the variability and the distribution of brain glucose metabolism after cardiac arrest and resuscitation in an adult rat model. MET...
Article
Full-text available
Oncogenic K-ras is capable to control tumor growth and progression by rewiring cancer metabolism. In vitro NIH-Ras cells convert glucose to lactate and use glutamine to sustain anabolic processes, but their in vivo environmental adaptation and multiple metabolic pathways activation ability is poorly understood. Here, we show that NIH-Ras cancer cel...
Article
Full-text available
Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells w...
Article
The factors that determine whether disseminated transformed cells in vivo yield neoplastic lesions have only been partially identified. We established an ad hoc model of peritoneal carcinomatosis by injecting colon carcinoma cells in mice. Tumor cells recruit inflammatory leukocytes, mostly macrophages, and generate neoplastic peritoneal lesions. P...
Article
Full-text available
Hypoxia-inducible factor 1α (HIF-1α) activity is one of the major players in hypoxia-mediated glioma progression and resistance to therapies, and therefore the focus of this study was the evaluation of HIF-1α modulation in relation to tumour response with the purpose of identifying imaging biomarkers able to document tumour response to treatment in...
Article
Full-text available
Anti-VEGF therapy perturbs tumor metabolism, severely impairing oxygen, glucose and ATP levels. In this study, we investigated the effects of anti-VEGF therapy in multiple experimental tumor models that differ in their glycolytic phenotypes, to gain insights into optimal modulation of the metabolic features of this therapy. Prolonged treatments ind...
Article
Full-text available
The anticancer activity of a novel pure 1,4-Diaryl-2-azetidinone (1), endowed with a higher solubility than the well known Combretastatin A4, is tested in mice. We previously reported that Compound (1) showed specific antiproliferative activity against duodenal and colon cancer cells, inducing activation of AMP-activated protein kinase and apoptosi...
Article
The aim of this study was to characterize a cell-based model for the molecular study of hypoxia-inducible factor (HIF)-1α activity, in the context of hypoxia, by means of different imaging techniques. Engineered U251-HRE glioma cells were used to analyze the molecular mechanisms underlying HIF-1α activity in vitro in relation to luciferase expressi...
Article
T acute lymphoblastic leukemia (T-ALL) is characterized by several genetic alterations and poor prognosis in about 20-25% of patients. Notably, about 60% of T-ALL shows increased Notch1 activity, due to activating NOTCH1 mutations, or alterations in the FBW7 gene, which confer to the cell a strong growth advantage. Therapeutic targeting of Notch si...
Article
Unlabelled: Hypoxic regions are present in different types of cancer and are a negative prognostic factor for disease progression and response to therapy. (18)F-fluoroazomycin-arabinofuranoside ((18)F-FAZA) and (64)Cu-diacetyl-bis(N4-methylthiosemicarbazone) ((64)Cu-ATSM) have been widely used to visualize hypoxic regions in preclinical and clinic...
Article
Full-text available
Reactive oxygen species (ROS) are regarded as hazardous by-products of mitochondrial respiration. In addition to the respiratory chain, specific ROS-generating systems have evolved. In particular, p66Shc is a mitochondrial redox protein that oxidizes cytochrome c to generate H2O2. Consistently, the deletion of p66Shc in cells and tissue results in...
Conference Paper
SPM has been widely used for the operator independent assessment of functional and molecular differences in human PET or MRI brain images. Despite the large diffusion of dedicated image systems and protocols, the use of SPM methodology to preclinical studies have been described in a limited number of studies, particularly for PET. Aim of this work...
Article
Decision support systems for the assisted medical diagnosis offer the main feature of giving assessments which are poorly affected from arbitrary clinical reasoning. Aim of this work was to assess the feasibility of a decision support system for the assisted diagnosis of brain cancer, such approach presenting potential for early diagnosis of tumors...
Article
Peritoneal carcinomatosis is the most common terminal feature of abdominal cancers. Interfering with the peritoneal immune microenvironment is a promising tool for combinational therapy. Preclinical studies on peritoneal carcinomatosis have been hampered by the limited availability of models as well as non-invasive methods to follow tumor growth. W...
Article
This study investigates whether positron emission tomography (PET) can be used to monitor the inflammatory response and its correlation with the later fibroproliferative phase in an experimental model of acute lung injury. Hydrochloric acid (0.1 N, pH 1, 1.5 ml/kg) was instilled into the right bronchus of mice. A group of mice underwent a micro-com...
Article
Full-text available
PET is widely used at the clinical and preclinical levels for tumor assessment and evaluation of treatment efficacy. Here, we established and took advantage of a preclinical model of peritoneal carcinomatosis to evaluate the contribution of inflammatory infiltrating macrophages in tumor progression that was followed using (18)F-FDG PET. Groups of m...
Article
Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice spontaneously develop hormone-dependent and hormone-independent prostate cancer (PC) that potentially resembles the human pathological condition. The aim of the study was to validate PET imaging as a reliable tool for in vivo assessment of disease biology and progression in TRAMP mice usi...

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Project (1)
Project
We employ a syngeneic mouse system to approach the role of HMGB1 in the fostering the onset and maintenance of mesothelioma and study the tumor micro-environment and the role of the immune system in the process. We also employ a 3D culture system (organoids) with cells generated from mouse and human tumors.