A5034571700- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- BRCA gene mutations in cancer
- Lung Cancer Treatments and Mutations
- Nutrition, Genetics, and Disease
- Cancer Immunotherapy and Biomarkers
- CRISPR and Genetic Engineering
- Neuroblastoma Research and Treatments
- Liver Disease Diagnosis and Treatment
- Hedgehog Signaling Pathway Studies
- DNA Repair Mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Diet, Metabolism, and Disease
- PARP inhibition in cancer therapy
- Immune Cell Function and Interaction
- Genomics and Phylogenetic Studies
- T-cell and B-cell Immunology
- Melanoma and MAPK Pathways
- Cancer and Skin Lesions
- Polyamine Metabolism and Applications
- Genomic variations and chromosomal abnormalities
- Hepatitis C virus research
- Lung Cancer Diagnosis and Treatment
- Glioma Diagnosis and Treatment
Sapienza University of Rome
2014-2023
Istituto Pasteur
2017-2023
Retina Institute
2018
Diamant (Germany)
2018
The University of Queensland
2018
Translational Research Institute
2018
NAFLD is a polygenic condition but the individual and cumulative contribution of identified genes remains to be established. To get additional insight into genetic architecture NAFLD, GWAS-identified GCKR, PPP1R3B, NCAN, LYPLAL1 TM6SF2 were resequenced by next generation sequencing in cohort 218 subjects 227 controls, where PNPLA3 rs738409 MBOAT7 rs641738 genotypes also obtained. A total 168 sequence variants detected 47 annotated as functional. When all functional within each gene...
A key mechanism driving colorectal cancer (CRC) development is the upregulation of MYC and its targets, including ornithine decarboxylase (ODC), a master regulator polyamine metabolism. Elevated polyamines promote tumorigenesis in part by activating DHPS-mediated hypusination translation factor eIF5A, thereby inducing biosynthesis. Thus, MYC, ODC eIF5A orchestrate positive feedback loop that represents an attractive therapeutic target for CRC therapy. Here we show combined inhibition induces...
Genomic studies performed through liquid biopsies widely elucidated the evolutionary trajectory of RAS mutant clones under selective pressure EGFR inhibitors in patients with wild type primary colorectal tumors. Similarly, disappearance plasma has been more recently reported some cancers, supporting for first time an unexpected negative selection mutations during clonal evolution mCRC. To date, extent conversion to disease at progression not clarified yet. As a proof concept, we...
Abstract MRE11 is a component of the MRE11/RAD50/NBS1 (MRN) complex, whose activity essential to control faithful DNA replication and prevent accumulation deleterious double-strand breaks. In humans, hypomorphic mutations in these genes lead damage response (DDR)-defective cancer-prone syndromes. Moreover, MRN complex dysfunction dramatically affects nervous system, where required restrain MYCN-dependent stress, during rapid expansion progenitor cells. MYCN activation, often due genetic...
Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC), based on the recognition of IgG-opsonized targets by low-affinity receptor for IgG FcγRIIIA/CD16, represents one main mechanisms which therapeutic antibodies (mAbs) mediate their antitumor effects. Besides ADCC, CD16 ligation also results in cytokine production, particular, NK-derived IFNγ is endowed with a well-recognized role shaping adaptive immune responses.Obinutuzumab glycoengineered anti-CD20 mAb...
The introduction of multigene panel testing for hereditary breast/ovarian cancer screening has greatly improved efficiency, speed, and costs. However, its clinical utility is still debated, mostly due to the lack conclusive evidences on impact newly discovered genetic variants risk evidence-based guidelines management their carriers. In this pilot study, we aimed test whether a systematic multiparametric characterization mutations could enhance sequencing. Out pool 367 families...
The term "neo-RAS wild-type" refers to the switch RAS wild-type disease in plasma circulating tumor DNA (ctDNA) from originally mutant colorectal cancers. Consistently, hypothesis re-determine mutational status ctDNA at progression mCRC opened a new perspective for clinically-based selection of patients be treated with EGFR inhibitors. Currently, genomic landscape is unknown. This prospective study aimed investigate clinical and features associated mutation clearance large cohort who...
Molecular alterations are not randomly distributed in colorectal cancer (CRC), but rather clustered on the basis of primary tumor location underlying importance sidedness. We aimed to investigate whether circulating cells (CTC) characterization might help clarify how different patterns dissemination be relative behavior left- (LCC) compared right-sided (RCC) cancers. retrospectively analyzed patients with metastatic CRC who had undergone standard baseline CTC evaluation before starting any...
Abstract MYCN drives aggressive behavior and refractoriness to chemotherapy, in several tumors. Since inactivation clinical settings is not achievable, alternative vulnerabilities of MYCN-driven tumors need be explored identify more effective less toxic therapies. We previously demonstrated that PARP inhibitors enhance MYCN-induced replication stress promote mitotic catastrophe, counteracted by CHK1. Here, we showed CHK1 synergized induce death neuroblastoma cells primary cultures...
Liquid biopsies have shown that, in RAS mutant colorectal cancer, the conversion to wild-type * status during course of disease is a frequent event, supporting concept that evolutionary landscape cancer can lead an unexpected negative selection clones. The aim present study was clarify whether mutation plasma might be drug-dependent. For this purpose, we used liquid biopsy compare rate from two groups originally mCRC patients: first treated with chemotherapy alone, while second combined...
Background Conventional methods used to identify BRCA1 and BRCA2 germline mutations in hereditary cancers, such as Sanger sequencing/multiplex ligation-dependent probe amplification (MLPA), are time-consuming expensive, due the large size of genes. The recent introduction next-generation sequencing (NGS) benchtop platforms offered a powerful alternative for mutation detection, dramatically improving speed efficiency DNA testing. Here we tested performance Ion Torrent PGM platform with...
As the knowledge on cancer genetic alterations progresses, it fosters need for more personalized therapeutic intervention in modern management. Recently, mutations KRAS, BRAF, and PIK3CA genes have emerged as important mechanisms of resistance to EGFR-targeted therapy metastatic colorectal (mCRC). Here we report first case a mCRC patient whose disease had progressed standard lines treatment which devised approach consisting vemurafenib (ZelborafTM) panitumumab (VectibixTM), based following...
Extensive molecular characterization of human colorectal cancer (CRC) via Next Generation Sequencing (NGS) indicated that genetic or epigenetic dysregulation a relevant, but limited, number pathways typically occurs in this tumor. The picture the disease is significantly complicated by frequent occurrence individually rare aberrations, which expand tumor heterogeneity. Inter- and intratumor heterogeneity very likely responsible for remarkable individual variability response to conventional...
Cutaneous squamous cell carcinoma (cSCC) is the second most common type of non-melanoma skin cancer. Platinum-based regimens have been an integral part palliative care for patients with locally advanced or metastatic disease. There no evidence efficacy later lines chemotherapy and targeted therapy has introduced as 'standard care'. Here we report on case elderly cSCC patient, resistant to conventional therapy, however successfully treated anti-epidermal growth factor receptor (EGFR) agent...
The clearance of RAS mutations in plasma circulating tumor DNA (ctDNA) from originally RAS-mutant metastatic colorectal cancer (mCRC) has been recently demonstrated. Clinical trials investigating whether mutant mCRC who "convert" to wild-type might benefit EGFR blockade are ongoing. Detection tumor-specific methylation alterations ctDNA suggested as a specific tool confirm the tumoral origin cell-free DNA. We monitored patients with at baseline (pre-treatment) (T0); after 4 months first-line...
The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting elevated heterogeneity disease. genetic alterations underlying this have been thoroughly characterized through omic approaches requiring efforts and costs. In order translate knowledge CRC molecular into a practical clinical approach, we utilized simplified Next Generation Sequencing (NGS) based platform screen cohort 77 patients treated with therapy. Samples...
Natural Killer (NK) cells contribute to the protective effects of vaccine-induced antibodies thanks low affinity receptor for IgG, FcγRIIIA/CD16, whose aggregation leads killing infected and IFNγ release, through which they potentiate adaptive immune responses. Forty-seven healthy young individuals undergoing either homologous (ChAdOx1-S/ChAdOx1-S) or heterologous (ChAdOx1-S/BNT162B2) SARS-CoV-2 vaccination settings were recruited. Peripheral blood samples collected immediately prior 8 weeks...
Abstract Background Historically, the molecular classification of colorectal cancer (CRC) was based on global genomic status, which identified microsatellite instability in mismatch repair (MMR) deficient CRC, and chromosomal MMR proficient CRC. With introduction immune checkpoint inhibitors, regained momentum as condition predicted sensitivity to possibly due both high tumor mutation burden (TMB) levels infiltrating lymphocytes. Conversely, CRC are mostly resistant immunotherapy. To better...
OPINION article Front. Oncol., 17 December 2019Sec. Gastrointestinal Cancers Volume 9 - 2019 | https://doi.org/10.3389/fonc.2019.01414