23 research outputs found
Cost-Consequence Analysis of Three Different Diagnostic Strategies in the First- and Second-Line Treatment of Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
BACKGROUND: Unlike the tissue one, liquid biopsy is a less invasive diagnostic method for the assessment of possible mutations of the tumor, based on the analysis of circulating free DNA (cfDNA) present in the plasma component of the blood. Because blood samples are easily obtainable, plasma biopsy is a non-invasive method, supplementing the more traditional biopsy techniques.AIM: A cost-consequence analysis was conducted to compare the adoption of three different diagnostic strategies in the first- and second-line treatment of locally advanced or metastatic NSCLC: i) tissue strategy (only tissue biopsy for first and second line), ii) combined strategy (first line: tissue biopsy. If unknown, liquid biopsy; second line: liquid biopsy. If negative, tissue biopsy) and iii) potential strategy (first line: tissue biopsy. If unknown or tissue ineligible, liquid biopsy; secondline: liquid biopsy. If negative, tissue biopsy).METHODS: A decision-analytic model was developed considering the Italian NHS’s perspective. We only evaluated direct medical costs (tissue biopsy, management of complications associated with tissue and liquid biopsies) borne by the NHS. The CCA was conducted over a time horizon of 1 year, assuming that for each patient with mNSCLC the diagnosticpathway (first- and second-line treatment) ended within such period. Key variables were tested in the sensitivity analysis.RESULTS: Considering both the first and the second line of treatment, the potential strategy constitutes the cost-effective alternative, characterized by an average cost per correctly identified case (€ 685) lower than that estimated for the combined strategy (€ 732) or for the tissue strategy (€ 1,004). The potential strategy remains cost-effective, also considering the results referred to the first- or second-line treatment only.CONCLUSION: The choice of a correct diagnostic strategy is crucial in order to optimize cancer therapies in the first- and second-line treatment of locally advanced or metastasized NSCLC. The addition to the diagnostic pathway of the liquid biopsy would correctly identify a greater number of cases, supporting the prescription of the best oncological therapy
Clinical Impact of two Different Diagnostic Strategies in the First- and Second-Line Treatment of Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer
BACKGROUND: A histopathological and mutational diagnosis has become a priority in the correct choice of the most appropriate cancer therapy for NSCLC. In the absence of a molecular analysis, the therapeutic choice will be directed towards platinum-based chemotherapy, thus preventing, in the presence of a specific mutation, the benefits deriving from the administration of a target therapies (TT).AIM: the present analysis was carried out with the aim of estimating the clinical impact, expressed in terms of progression free survival (PFS), associated with the use of the combined strategy (tissue biopsy and liquid biopsy) or the tissue strategy in the EGFR+ mNSCLC population.METHODS: A pre-existing cost-consequence model was adapted to estimate the annual number of mNSCLC patients with or without the EGFR mutation in order to decide the oncological treatment to be administered in first (1L) or second line (2L). In 1L, against the presence of the EGFR mutation, the administration of a Tyrosine Kinase Inhibitor (TKI), such as osimertinib, gefitinib, erlotinib or afatinib, was considered; in the absence of the EGFR mutation, the administration ofstandard platinum-based chemotherapy was instead considered. With reference to 2L, in the presence of the EGFR T790M mutation, only osimertinib was considered. In the absence of the EGFR T790M mutation, the administration of the standard platinum-based chemotherapy was also considered. The PFS data associated with each of the drugs considered were extrapolated from the respective clinical studies. Key variables were tested in the sensitivity analysis.RESULTS: The adoption of the combined strategy (tissue biopsy and liquid biopsy), by virtue of a greater number of patients treated with TKIs, would make it possible to increase the average PFS in the range of 1.1-3,7 months in the 1L and by 1.4 months in the 2L.CONCLUSION: These results show how the adoption of a correct diagnostic strategy is critical in order to optimize the choice of the therapeutic path in the 1L and 2L of mNSCLC. The addition of the liquid biopsy to the classic diagnostic path (tissue biopsy) would in fact allow to obtain an increase in therapeutic efficacy (average PFS)
Personalized medicine: biomarkers and companion diagnostics
Great expectations are bound to the current evolution of medicine to personalized medicine. Thanks to rapid advances in genomics and molecular biology, new markers can be revealed for the presence of or susceptibility to a disease, or response to treatment. On such markers, diagnostic tests can be based; companion diagnostics (CDx, often called In Vitro devices) are diagnostic tests "coupled" with a therapeutic drug, aimed at assessing its applicability to a specific class of patients. As well as exemplifying some already implemented CDx applications, the purpose of this article is to highlight potentials and problems of personalized medicine today. In particular, the opportunity is analyzed for the co-development of a new drug and its CDx, through a parallel base research. This approach is promoted by the regulatory agencies but, due to scientific and economic factors implicit in the process, it is taking-off slowly. Personalized medicine deserves to grow and to expand, first of all because it simultaneously promises to substantially improve patient care and to make big costs savings for healthcare systems. From this point of view, all stakeholders (diagnostics manufacturers, clinical testing laboratories, pharmaceutical firms, the Department of health, and other bodies) should talk to each other in order to support the advancement of personalized medicine
GRUND 2008 nella sub area geografica 16 (GSA 16, Stretto di Sicilia): relazione finale
Il progetto Grund, finanziato a partire dal 1985 dapprima dalla D.G. Pesca e Acquacolura del Ministero per le politiche agricole, alimentari e forestali (MIPAAF) con i fondi della legge 41, in seguito dal MIPAAF e dalla DG IV della Commissione Europea, ha l’obiettivo generale di valutare la distribuzione, l’abbondanza e la composizione per taglia delle specie oggetto di pesca presenti nei mari Italiani.
L’Istituto di ricerche sulle Risorse Marine e l’Ambiente, Sezione di Mazara del Vallo di IAMC-CNR, effettua campagne di ricerca in mare nella GSA 16 (FAO, 2001) dello Stretto di Sicilia, tramite rete a strascico (trawl survey), sin dalla primavera del 1985, con l’obiettivo generale di studiare l’abbondanza ed i cicli vitali delle risorse demersali e di stimarne lo stato di sfruttamento
Insulin Receptor Isoform A and Insulin-like Growth Factor II as Additional Treatment Targets in Human Osteosarcoma
Abstract
Despite the frequent presence of an insulin-like growth factor I receptor (IGFIR)-mediated autocrine loop in osteosarcoma (OS), interfering with this target was only moderately effective in preclinical studies. Here, we considered other members of the IGF system that might be involved in the molecular pathology of OS. We found that, among 45 patients with OS, IGF-I and IGFBP-3 serum levels were significantly lower, and IGF-II serum levels significantly higher, than healthy controls. Increased IGF-II values were associated with a decreased disease-free survival. After tumor removal, both IGF-I and IGF-II levels returned to normal values. In 23 of 45 patients, we obtained tissue specimens and found that all expressed high mRNA level of IGF-II and >IGF-I. Also, isoform A of the insulin receptor (IR-A) was expressed at high level in addition to IGFIR and IR-A/IGFIR hybrids receptors (HRA). These receptors were also expressed in OS cell lines, and simultaneous impairment of IGFIR, IR, and Hybrid-Rs by monoclonal antibodies, siRNA, or the tyrosine kinase inhibitor BMS-536924, which blocks both IGFIR and IR, was more effective than selective anti-IGFIR strategies. Also, anti–IGF-II-siRNA treatment in low-serum conditions significantly inhibited MG-63 OS cells that have an autocrine circuit for IGF-II. In summary, IGF-II rather than IGF-I is the predominant growth factor produced by OS cells, and three different receptors (IR-A, HRA, and IGFIR) act complementarily for an IGF-II–mediated constitutive autocrine loop, in addition to the previously shown IGFIR/IGF-I circuit. Cotargeting IGFIR and IR-A is more effective than targeting IGF-IR alone in inhibiting OS growth. [Cancer Res 2009;69(6):2443–52
Piano di Lavoro Nazionale Raccolta Dati Alieutici 2017-2019 Rapporto tecnico annuale
Campionamento biologico delle specie demersali e dei piccoli pelagici (GSA16
New insight on a Group A Streptococcus protective antigen contributing to bacterial cell division
Bioinformatic analysis of Group A Streptococcus (GAS) genomes aiming at the identification of new vaccine antigens, revealed the presence of a gene coding for a putative surface-associated protein, named GAS40, inducing protective antibodies in an animal model of sepsis. The aim of our study was to unravel the involvement of GAS40 in cell division processes and to identify the putative interactor. Firstly, bioinformatic analysis showed that gas40 shares homology with ezrA, a gene coding for a negative regulator of Z-ring formation during cell division process. Both scanning and transmission electron microscopy indicated morphological differences between wild-type and the GAS40 knock-out mutant strain, with the latter showing an impaired capacity to divide resulting in the formation of very long chains. Moreover, when the localization of the antigen on the bacterial surface was analyzed, we found that in bacteria grown at exponential phase GAS40 specifically localized at septum, indicating a possible role in cell division. Furthermore, by ELISA and co-sedimentation assays, we found that GAS40 is able to interact with FtsZ, a protein involved in Z-ring formation during cell division process. These data together with the co-localization of GAS40/FtsZ at bacterial septum demonstrated by by confocal microscopy, strongly support the hypothesis for a key role of GAS40 in bacterial cell division
Personalized medicine: biomarkers and companion diagnostics
Great expectations are bound to the current evolution of medicine to personalized medicine. Thanks to rapid advances in genomics and molecular biology, new markers can be revealed for the presence of or susceptibility to a disease, or response to treatment. On such markers, diagnostic tests can be based; companion diagnostics (CDx, often called In Vitro devices) are diagnostic tests “coupled” with a therapeutic drug, aimed at assessing its applicability to a specific class of patients. As well as exemplifying some already implemented CDx applications, the purpose of this article is to highlight potentials and problems of personalized medicine today. In particular, the opportunity is analyzed for the co-development of a new drug and its CDx, through a parallel base research. This approach is promoted by the regulatory agencies but, due to scientific and economic factors implicit in the process, it is taking-off slowly. Personalized medicine deserves to grow and to expand, first of all because it simultaneously promises to substantially improve patient care and to make big costs savings for healthcare systems. From this point of view, all stakeholders (diagnostics manufacturers, clinical testing laboratories, pharmaceutical firms, the Department of health, and other bodies) should talk to each other in order to support the advancement of personalized medicine
CAMPAGNA di ricerca in mare: Sezione G – MEDITS 2011 Sub-area Geografica (GSA) 16 - Stretto di Sicilia. Rapporto tecnico ed analisi finale
La campagna scientifica Medits, nell’ambito del Programma nazionale Italiano per la raccolta dei dati alieutici (Reg. CE n°199/2008 e n°665/2008), ha l’obiettivo generale di valutare la distribuzione, l’abbondanza e la composizione per taglia delle specie oggetto di pesca presenti nei mari Italiani.
L’Istituto di ricerche per l’Ambiente Marino Costiero (IAMC), sede di Mazara del Vallo, del Consiglio nazionale delle Ricerche (CNR), effettua campagne di ricerca in mare nella GSA 16 (FAO, 2001) dello Stretto di Sicilia, tramite rete a strascico (trawl survey), sin dalla primavera del 1985, con l’obiettivo generale di studiare l’abbondanza ed i cicli vitali delle risorse demersali e di stimarne lo stato di sfruttamento
Campagna di ricerca in mare: Sezione G – MEDITS 2010 Sub-area Geografica (GSA)16 - Stretto di Sicilia
La campagna scientifica Medits, nell’ambito della Sezione G del Programma Nazionale Italiano per la Raccolta dei Dati Alieutici (Reg. Ce. N°199/2008; N°665/2008 e decisione della commissione N°949/2008), ha l’obiettivo generale di valutare la distribuzione, l’abbondanza e la composizione per taglia delle specie oggetto di pesca presenti nei mari Italiani. La campagna (di seguito indicata come MEDSp10) ha interessato lo Stretto di Sicilia per un’area complessiva di 31386 km2