Publications by authors named "Raffaella Marconi"

8 Publications

  • Page 1 of 1

Novel cancer therapies for advanced cutaneous melanoma: The added value of radiomics in the decision making process-A systematic review.

Cancer Med 2020 03 17;9(5):1603-1612. Epub 2020 Jan 17.

Medical Physics and Expert Systems Laboratory, Department of Research and Advanced Technologies, Istituti Fisioterapici Ospitalieri -Regina Elena Institute IRCCS, Rome, Italy.

Advanced malignant melanoma represents a public health matter due to its rising incidence and aggressiveness. Novel therapies such as immunotherapy are showing promising results with improved progression free and overall survival in melanoma patients. However, novel targeted and immunotherapies could generate atypical patterns of response which are nowadays a big challenge since imaging criteria (ie Recist 1.1) have not been proven to be always reliable to assess response. Radiomics and in particular texture analysis (TA) represent new quantitative methodologies which could reduce the impact of these limitations providing most robust data in support of clinical decision process. The aim of this paper was to review the state of the art of radiomics/TA when it is applied to the imaging of metastatic melanoma patients.
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http://dx.doi.org/10.1002/cam4.2709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050080PMC
March 2020

Cytokine Modulation in Breast Cancer Patients Undergoing Radiotherapy: A Revision of the Most Recent Studies.

Int J Mol Sci 2019 Jan 17;20(2). Epub 2019 Jan 17.

Laboratory of Medical Physics and Expert Systems, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.

Breast cancer (BC) is the most common tumor and the second cause for cancer-related death in women worldwide, although combined treatments are well-established interventions. Several effects seem to be responsible for poor outcomes in advanced or triple-negative BC patients. Focusing on the interaction of ionizing radiation with tumor and normal tissues, the role of cytokine modulation as a surrogate of immunomodulation must still be explored. In this work, we carried out an overview of studies published in the last five years involving the cytokine profile in BC patients undergoing radiotherapy. The goal of this review was to evaluate the profile and modulation of major cytokines and interleukins as potential biomarkers of survival, treatment response, and toxicity in BC patient undergoing radiotherapy. Out of 47 retrieved papers selected using PubMed search, 15 fulfilled the inclusion criteria. Different studies reported that the modulation of specific cytokines was time- and treatment-dependent. Radiotherapy (RT) induces the modulation of inflammatory cytokines up to 6 months for most of the analyzed cytokines, which in some cases can persist up to several years post-treatment. The role of specific cytokines as prognostic and predictive of radiotherapy outcome is critically discussed.
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http://dx.doi.org/10.3390/ijms20020382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359111PMC
January 2019

Very low intensity ultrasounds as a new strategy to improve selective delivery of nanoparticles-complexes in cancer cells.

J Exp Clin Cancer Res 2019 Jan 3;38(1). Epub 2019 Jan 3.

Laboratory of Medical Physics and Expert Systems, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.

Background: The possibility to combine Low Intensity UltraSound (LIUS) and Nanoparticles (NP) could represent a promising strategy for drugs delivery in tumors difficult to treat overcoming resistance to therapies. On one side the NP can carry drugs that specifically target the tumors on the other the LIUS can facilitate and direct the delivery to the tumor cells. In this study, we investigated whether Very Low Intensity UltraSound (VLIUS), at intensities lower than 120 mW/cm, might constitute a novel strategy to improve delivery to tumor cells. Thus, in order to verify the efficacy of this novel modality in terms of increase selective uptake in tumoral cells and translate speedily in clinical practice, we investigated VLIUS in three different in vitro experimental tumor models and normal cells adopting three different therapeutic strategies.

Methods: VLIUS at different intensities and exposure time were applied to tumor and normal cells to evaluate the efficiency in uptake of labeled human ferritin (HFt)-based NP, the delivery of NP complexed Firefly luciferase reported gene (lipoplex-LUC), and the tumor-killing of chemotherapeutic agent.

Results: Specifically, we found that specific VLIUS intensity (120 mW/cm) increases tumor cell uptake of HFt-based NPs at specific concentration (0.5 mg/ml). Similarly, VLIUS treatments increase significantly tumor cells delivery of lipoplex-LUC cargos. Furthermore, of interest, VLIUS increases tumor killing of chemotherapy drug trabectedin in a time dependent fashion. Noteworthy, VLIUS treatments are well tolerated in normal cells with not significant effects on cell survival, NPs delivery and drug-induced toxicity, suggesting a tumor specific fashion.

Conclusions: Our data shed novel lights on the potential application of VLIUS for the design and development of novel therapeutic strategies aiming to efficiently deliver NP loaded cargos or anticancer drugs into more aggressive and unresponsive tumors niche.
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http://dx.doi.org/10.1186/s13046-018-1018-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318873PMC
January 2019

Radiobiological Optimization in Lung Stereotactic Body Radiation Therapy: Are We Ready to Apply Radiobiological Models?

Front Oncol 2017 8;7:321. Epub 2018 Jan 8.

Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy.

Lung tumors are often associated with a poor prognosis although different schedules and treatment modalities have been extensively tested in the clinical practice. The complexity of this disease and the use of combined therapeutic approaches have been investigated and the use of high dose-rates is emerging as effective strategy. Technological improvements of clinical linear accelerators allow combining high dose-rate and a more conformal dose delivery with accurate imaging modalities pre- and during therapy. This paper aims at reporting the state of the art and future direction in the use of radiobiological models and radiobiological-based optimizations in the clinical practice for the treatment of lung cancer. To address this issue, a search was carried out on PubMed database to identify potential papers reporting tumor control probability and normal tissue complication probability for lung tumors. Full articles were retrieved when the abstract was considered relevant, and only papers published in English language were considered. The bibliographies of retrieved papers were also searched and relevant articles included. At the state of the art, dose-response relationships have been reported in literature for local tumor control and survival in stage III non-small cell lung cancer. Due to the lack of published radiobiological models for SBRT, several authors used dose constraints and models derived for conventional fractionation schemes. Recently, several radiobiological models and parameters for SBRT have been published and could be used in prospective trials although external validations are recommended to improve the robustness of model predictive capability. Moreover, radiobiological-based functions have been used within treatment planning systems for plan optimization but the advantages of using this strategy in the clinical practice are still under discussion. Future research should be directed toward combined regimens, in order to potentially improve both local tumor control and survival. Indeed, accurate knowledge of the relevant parameters describing tumor biology and normal tissue response is mandatory to correctly address this issue. In this context, the role of medical physicists and the AAPM in the development of radiobiological models is crucial for the progress of developing specific tool for radiobiological-based optimization treatment planning.
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http://dx.doi.org/10.3389/fonc.2017.00321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766682PMC
January 2018

A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger?

PLoS One 2017 21;12(2):e0171559. Epub 2017 Feb 21.

Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy.

Background: Preclinical in vivo studies using small animals are considered crucial in translational cancer research and clinical implementation of novel treatments. This is of paramount relevance in radiobiology, especially for any technological developments permitted to deliver high doses in single or oligo-fractionated regimens, such as stereotactic ablative radiotherapy (SABR). In this context, clinical success in cancer treatment needs to be guaranteed, sparing normal tissue and preventing the potential spread of disease or local recurrence. In this work we introduce a new dose-response relationship based on relevant publications concerning preclinical models with regard to delivered dose, fractionation schedule and occurrence of biological effects on non-irradiated tissue, abscopal effects.

Methods: We reviewed relevant publications on murine models and the abscopal effect in radiation cancer research following PRISMA methodology. In particular, through a log-likelihood method, we evaluated whether the occurrence of abscopal effects may be related to the biologically effective dose (BED). To this aim, studies accomplished with different tumor histotypes were considered in our analysis including breast, colon, lung, fibrosarcoma, pancreas, melanoma and head and neck cancer. For all the tumors, the α / β ratio was assumed to be 10 Gy, as generally adopted for neoplastic cells.

Results: Our results support the hypothesis that the occurrence rate of abscopal effects in preclinical models increases with BED. In particular, the probability of revealing abscopal effects is 50% when a BED of 60 Gy is generated.

Conclusion: Our study provides evidence that SABR treatments associated with high BEDs could be considered an effective strategy in triggering the abscopal effect, thus shedding light on the promising outcomes revealed in clinical practice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171559PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319701PMC
August 2017

Physical mapping in highly heterozygous genomes: a physical contig map of the Pinot Noir grapevine cultivar.

BMC Genomics 2010 Mar 26;11:204. Epub 2010 Mar 26.

Istituto di Genomica Applicata, Parco Scientifico e Tecnologico di Udine Luigi Danieli, Via J Linussio 51, 33100 Udine, Italy.

Background: Most of the grapevine (Vitis vinifera L.) cultivars grown today are those selected centuries ago, even though grapevine is one of the most important fruit crops in the world. Grapevine has therefore not benefited from the advances in modern plant breeding nor more recently from those in molecular genetics and genomics: genes controlling important agronomic traits are practically unknown. A physical map is essential to positionally clone such genes and instrumental in a genome sequencing project.

Results: We report on the first whole genome physical map of grapevine built using high information content fingerprinting of 49,104 BAC clones from the cultivar Pinot Noir. Pinot Noir, as most grape varieties, is highly heterozygous at the sequence level. This resulted in the two allelic haplotypes sometimes assembling into separate contigs that had to be accommodated in the map framework or in local expansions of contig maps. We performed computer simulations to assess the effects of increasing levels of sequence heterozygosity on BAC fingerprint assembly and showed that the experimental assembly results are in full agreement with the theoretical expectations, given the heterozygosity levels reported for grape. The map is anchored to a dense linkage map consisting of 994 markers. 436 contigs are anchored to the genetic map, covering 342 of the 475 Mb that make up the grape haploid genome.

Conclusions: We have developed a resource that makes it possible to access the grapevine genome, opening the way to a new era both in grape genetics and breeding and in wine making. The effects of heterozygosity on the assembly have been analyzed and characterized by using several complementary approaches which could be easily transferred to the study of other genomes which present the same features.
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http://dx.doi.org/10.1186/1471-2164-11-204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865496PMC
March 2010

A physical map of the heterozygous grapevine 'Cabernet Sauvignon' allows mapping candidate genes for disease resistance.

BMC Plant Biol 2008 Jun 13;8:66. Epub 2008 Jun 13.

UMR de Génomique Végétale, INRA-CNRS-UEVE, 2, Rue Gaston Crémieux, CP5708, 91057 Evry Cedex, France.

Background: Whole-genome physical maps facilitate genome sequencing, sequence assembly, mapping of candidate genes, and the design of targeted genetic markers. An automated protocol was used to construct a Vitis vinifera 'Cabernet Sauvignon' physical map. The quality of the result was addressed with regard to the effect of high heterozygosity on the accuracy of contig assembly. Its usefulness for the genome-wide mapping of genes for disease resistance, which is an important trait for grapevine, was then assessed.

Results: The physical map included 29,727 BAC clones assembled into 1,770 contigs, spanning 715,684 kbp, and corresponding to 1.5-fold the genome size. Map inflation was due to high heterozygosity, which caused either the separation of allelic BACs in two different contigs, or local mis-assembly in contigs containing BACs from the two haplotypes. Genetic markers anchored 395 contigs or 255,476 kbp to chromosomes. The fully automated assembly and anchorage procedures were validated by BAC-by-BAC blast of the end sequences against the grape genome sequence, unveiling 7.3% of chimerical contigs. The distribution across the physical map of candidate genes for non-host and host resistance, and for defence signalling pathways was then studied. NBS-LRR and RLK genes for host resistance were found in 424 contigs, 133 of them (32%) were assigned to chromosomes, on which they are mostly organised in clusters. Non-host and defence signalling genes were found in 99 contigs dispersed without a discernable pattern across the genome.

Conclusion: Despite some limitations that interfere with the correct assembly of heterozygous clones into contigs, the 'Cabernet Sauvignon' physical map is a useful and reliable intermediary step between a genetic map and the genome sequence. This tool was successfully exploited for a quick mapping of complex families of genes, and it strengthened previous clues of co-localisation of major NBS-LRR clusters and disease resistance loci in grapevine.
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http://dx.doi.org/10.1186/1471-2229-8-66DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442077PMC
June 2008

Colour variation in red grapevines (Vitis vinifera L.): genomic organisation, expression of flavonoid 3'-hydroxylase, flavonoid 3',5'-hydroxylase genes and related metabolite profiling of red cyanidin-/blue delphinidin-based anthocyanins in berry skin.

BMC Genomics 2006 Jan 24;7:12. Epub 2006 Jan 24.

Dipartimento di Scienze Agrarie e Ambientali, University of Udine, via delle Scienze 208, 33100 Udine, Italy.

Background: Structural genes of the phenyl-propanoid pathway which encode flavonoid 3'- and 3',5'-hydroxylases (F3'H and F3'5'H) have long been invoked to explain the biosynthesis of cyanidin- and delphinidin-based anthocyanin pigments in the so-called red cultivars of grapevine. The relative proportion of the two types of anthocyanins is largely under genetic control and determines the colour variation among red/purple/blue berry grape varieties and their corresponding wines.

Results: Gene fragments of VvF3'H and VvF3'5'H, that were isolated from Vitis vinifera 'Cabernet Sauvignon' using degenerate primers designed on plant homologous genes, translated into 313 and 239 amino acid protein fragments, respectively, with up to 76% and 82% identity to plant CYP75 cytochrome P450 monooxygenases. Putative function was assigned on the basis of sequence homology, expression profiling and its correlation with metabolite accumulation at ten different ripening stages. At the onset of colour transition, transcriptional induction of VvF3'H and VvF3'5'H was temporally coordinated with the beginning of anthocyanin biosynthesis, the expression being 2-fold and 50-fold higher, respectively, in red berries versus green berries. The peak of VvF3'5'H expression was observed two weeks later concomitantly with the increase of the ratio of delphinidin-/cyanidin-derivatives. The analysis of structural genomics revealed that two copies of VvF3'H are physically linked on linkage group no. 17 and several copies of VvF3'5'H are tightly clustered and embedded into a segmental duplication on linkage group no. 6, unveiling a high complexity when compared to other plant flavonoid hydroxylase genes known so far, mostly in ornamentals.

Conclusion: We have shown that genes encoding flavonoid 3'- and 3',5'-hydroxylases are expressed in any tissues of the grape plant that accumulate flavonoids and, particularly, in skin of ripening red berries that synthesise mostly anthocyanins. The correlation between transcript profiles and the kinetics of accumulation of red/cyanidin- and blue/delphinidin-based anthocyanins indicated that VvF3'H and VvF3'5'H expression is consistent with the chromatic evolution of ripening bunches. Local physical maps constructed around the VvF3'H and VvF3'5'H loci should help facilitate the identification of the regulatory elements of each isoform and the future manipulation of grapevine and wine colour through agronomical, environmental and biotechnological tools.
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http://dx.doi.org/10.1186/1471-2164-7-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1403756PMC
January 2006