Lara Paracchini

Lara Paracchini
Humanitas University · Cancer Pharmacology

Doctor of Philosophy

About

44
Publications
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951
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Publications

Publications (44)
Article
Full-text available
Purpose: Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic diseases, with survival rate virtually unchanged for the past 30 years. EOC comprises different histotypes with molecular and clinical heterogeneity, but up till now the present gold standard platinum-based treatment has been conducted without any patient stratification...
Article
Full-text available
To date, there are no biomarkers that define a patient subpopulation responsive to bevacizumab (BEV), an effective treatment option for advanced ovarian carcinoma (OC). In the context of the MITO16A/MaNGO OV‐2 trial, a Phase IV study of chemotherapy combined with BEV in first‐line treatment of advanced OC, we evaluated TP53 mutations by next‐genera...
Article
TPS5628 Background: PAOLA-1/ENGOT-ov25 trial demonstrated that Olaparib (O) plus Bevacizumab (B) determined a significant survival benefit in patients (pts) with advanced, high-grade, epithelial ovarian, peritoneal and/or fallopian-tube cancer (HEOC) presenting defects of homologous recombination repair system (HRD+) in clinical response after firs...
Article
Background. Although 80% of high grade serous ovarian cancer (HGSOC) patients are initially responsive to platinum (Pt)-based chemotherapy, the majority of them experience relapse with a progressive Pt-resistant disease. One of the most challenging issue that hampers the possibility to effectively treat relapsed disease is the lack of biological in...
Article
Background: Although 80% of high grade serous ovarian cancer (HGSOC) patients are initially responsive to platinum (Pt)-based chemotherapy, the majority of them experience relapse with a progressive Pt-resistant disease. One of the most challenging issues that hampers the possibility to effectively treat relapsed disease is the lack of biological i...
Article
Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecologica...
Article
High grade serous ovarian carcinoma (HGSOC) is a systemic malignancy characterized by metastatic lesions that spread within the peritoneal cavity. Despite initial sensibility to platinum-based chemotherapy, more than 80% of patients experience a relapse and acquire chemoresistance. From a genomic point of view, HGSOC shows a high level of inter- an...
Article
Full-text available
We have previously demonstrated that longitudinal untargeted analysis of plasma samples withdrawn from patients with high-grade serous ovarian cancer (HGS-EOC) can intercept the presence of molecular recurrence (TRm) earlier than the diagnosis of clinical recurrence (TRc). This finding opens a clinical important temporal window to acquire through p...
Article
Full-text available
Although clinical antitumor activity of Tumor Treating Fields (TTFields) has been reported in malignant pleural mesothelioma (MPM) patients, the mechanisms behind the different selectivity displayed by the various MPM histotypes to this physical therapy has not been elucidated yet. Taking advantage of the development of well characterized human MPM...
Article
Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a 5-year survival rate of less than 10% and it remains a cancer lacking effective therapy options when tumors progress. The development of novel drug regimens for MPM treatment have been limited during the last two decades, with the exception of combinations including immune chec...
Article
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Pleural mesothelioma (PM) is an aggressive tumor with few therapeutic options. Although patients with epithelioid PM (ePM) survive longer than non-epithelioid PM (non-ePM), heterogeneity of tumor response in ePM is observed. The role of the tumor immune microenvironment (TIME) in the development and progression of PM is currently considered a promi...
Conference Paper
p>Despite the increasing knowledge of the biology of malignant pleural mesothelioma (MPM), patients with this diagnosis still have a poor prognosis with a 5-year survival rate of lower than 10%. The effectiveness demonstrated by Tumor Treating Fields (TTFields) in combination with chemotherapy in preclinical experiments and in MPM patients (NCT0239...
Article
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Simple Summary As for other neoplasms, liquid biopsy can be a useful tool to improve diagnosis and to monitor the response to therapy of high-grade serous epithelial ovarian cancer, which is the most common and lethal gynecological malignancy. In this paper, we provide an overview of the available knowledge on the current status and future opportun...
Article
Full-text available
Purpose: High-Grade Serous Epithelial Ovarian Cancer (HGS-EOC), is defined by high levels of somatic copy number alterations (SCNA) with marked spatial and temporal tumor heterogeneity. Biomarkers serving to monitor drug response and detect disease recurrence are lacking, a fact which reflects an unmet clinical need. Experimental design: 185 pla...
Conference Paper
p> Background: The low five-years survival rate of High Grade Serous Epithelial Ovarian Cancer (HGS-EOC) is mainly related to late diagnosis. The anticipation of diagnosis constitutes a crucial step to increase the curability of this disease. Aim: This study explores an innovative potential HGS-EOC screening approach exploiting PAP tests routinely...
Article
Full-text available
Importance The low 5-year survival rate of women with high-grade serous epithelial ovarian cancer (HGS-EOC) is related to its late diagnosis; thus, improvement in diagnosis constitutes a crucial step to increase the curability of this disease. Objective To determine whether the presence of the clonal pathogenic TP53 variant detected in matched pri...
Article
Full-text available
High‐grade serous ovarian cancer (HGS‐EOCs) is generally sensitive to front‐line platinum (Pt)‐based chemotherapy although most patients at an advanced stage relapse with progressive resistant disease. Clinical or molecular data to identify primary resistant cases at diagnosis are not yet available. HGS‐EOC biopsies from 105 Pt‐sensitive (Pt‐s) and...
Article
Full-text available
Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs. It is characterized by a complex histopathological and molecular heterogeneity, and it is composed of five main histological subtypes (mucinous, endometrioid, clear cell and high, and low grade serous), which have peculiar genetic, molecular, and clinical characteristics. As...
Conference Paper
Introduction/Background The activation of TGFβ pathway in advanced stage high-grade serous ovarian cancer (HGSOC) has been found to be related to short progression free survival (PFS) and overall survival (OS). miRNA181a-5p was found to be a proxy of TGFβ activation. This prognostic role has been identified only in cohorts with low surgical complex...
Conference Paper
Introduction/Background High-grade serous ovarian carcinoma (HGSOC), the most common and deadly epithelial ovarian cancer histotype is characterized by a heterogeneous genomic landscape. After surgery, all patients are treated with adjuvant platinum (Pt)-based chemotherapy to which the response is heterogeneous, ranging from cases sensitive (Platin...
Article
Full-text available
High‐grade serous epithelial ovarian cancer (HGS‐EOC) is a systemic disease, with marked intra and interpatient tumor heterogeneity. The issue of spatial and temporal heterogeneity has long been overlooked, hampering the possibility to identify those genomic alterations that persist, before and after therapy, in the genome of all tumor cells across...
Article
Full-text available
Background The typical familial form of Alzheimer’s disease (FAD) accounts for about 5% of total Alzheimer’s disease (AD) cases. Presenilins (PSEN1 and PSEN2) and amyloid-β (A4) precursor protein (APP) genes carry all reported FAD-linked mutations. However, other genetic loci may be involved in AD. For instance, seizure-related gene 6 (SEZ6) has be...
Article
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Background: Lurbinectedin is a novel anticancer agent currently undergoing late-stage (Phase II /III) clinical evaluation in platinum-resistant ovarian, BRCA1/2-mutated breast and small-cell lung cancer. Lurbinectedin is structurally related to trabectedin and it inhibits active transcription and the DNA repair machinery in tumour cells. Methods:...
Article
High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic neoplasm, with five-year survival rate below 30%. Early disease detection is of utmost importance to improve HGSOC cure rate. Sera from 168 HGSOC patients and 65 healthy controls were gathered together from two independent collections and stratified into a training set, for...
Article
We recently discovered that forebrain activation of the IL-1 receptor/Toll-like receptor (IL-1R1/TLR4) innate immunity signal plays a pivotal role in neuronal hyperexcitability underlying seizures in rodents. Since this pathway is activated in neurons and glia in human epileptogenic foci, it represents a potential target for developing drugs interf...
Article
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This study was designed to investigate the mode of action of trabectedin in myelomonocytic leukemia cells by applying systems biology approaches to mine gene expression profiling data and pharmacological assessment of the cellular effects. Significant enrichment was found in regulons of target genes inferred for specific transcription factors, amon...
Article
Full-text available
Purpose: Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs and is characterized by good prognosis with fewer than 20% of patients relapsing. As it occurs less frequently than advanced stage EOC, its molecular features have not been thoroughly investigated. We have demonstrated that in stage I EOC hsa-miR-200c-3p can predict...
Article
Objectives: To define the features of human amniotic mesenchymal stromal cell secretome and its protective properties in experimental models of acute brain injury. Design: Prospective experimental study. Setting: Laboratory research. Subjects: C57Bl/6 mice. Interventions: Mice subjected to sham or traumatic brain injury by controlled corti...
Article
Full-text available
Stage III/IV epithelial ovarian cancer (EOC) is a systemic disease. The clonal relationship among different tumor lesions at diagnosis (spatial heterogeneity) and how tumor clonal architecture evolves over time (temporal heterogeneity) have not yet been defined. Such knowledge would help to develop new target-based strategies, as biomarkers which c...
Article
Background Clinical and pathological parameters of patients with epithelial ovarian cancer (EOC) do not thoroughly predict patient outcome. Despite the good outcome of stage I EOC compared to stage III-IV, the risk assessment and treatments are almost the same. However, only 20% of stage I EOC relapse and die, meaning that only a proportion of pati...
Article
Background Neo-adjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with unresectable advanced epithelial ovarian cancer (EOC). The molecular events leading to platinum response in NACT settings has hitherto not been explored. In the present work, longitudinal changes of miRNA expression profile were inves...
Article
The majority of patients with stage III-IV epithelial ovarian cancer (EOC) relapse after initially responding to platinum-based chemotherapy, and develop resistance. The genomic features involved in drug resistance are unknown. To unravel some of these features we investigated the mutational profile of genes involved in pathways related to drug sen...
Article
Trabectedin is a marine natural product, approved in Europe for the treatment of soft tissue sarcoma and relapsed ovarian cancer. Clinical and experimental evidence indicates that trabectedin is particularly effective against myxoid liposarcomas where response is associated to regression of capillary networks. Here we investigated the mechanism of...
Article
Introduction. Within stage I epithelial ovarian cancer (EOC), the current clinic-pathological parameters, like tumor grade, fail to accurately stratify patient prognosis and it is therefore crucial for optimal treatment that the biological properties of stage I EOCs are further elucidated. We have previously demonstrated miR-200c as a predictor of...

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