Marina Pisano - Academia.edu (original) (raw)

Papers by Marina Pisano

Journal of Personalized Medicine

Lung cancer is one of the most common and lethal cancers worldwide. Numerous medications targetin... more Lung cancer is one of the most common and lethal cancers worldwide. Numerous medications targeting specific molecular alterations in non-small cell lung cancer have been introduced in the last decade and have revolutionized the clinical management of the disease. Their use has brought to a parallel evolution of molecular testing techniques to identify alterations in druggable molecular targets within the genetic material of the tumors. To perform molecular testing, biopsy or surgery tissue specimens are needed, which in addition allow the histological characterization of the tumors. Unfortunately, in real-life practice not all the patients are suitable for biopsy or surgery procedures. The use of liquid biopsy for blood extracted tumoral DNA analysis is a promising approach in unbiopsied cases, but it is also weighted by several methodological and technical limitations. We report here a case of histologically undiagnosed lung cancer managed with a liquid biopsy and subsequently with...

Journal of Clinical Oncology

3577 Background: The rechallenge with EGFR inhibitors represents an emerging strategy for anti-EG... more 3577 Background: The rechallenge with EGFR inhibitors represents an emerging strategy for anti-EGFR pre-treated patients with RAS wild type colorectal cancer (CRC). Unfortunately definitive selection criteria for anti-EGFR rechallenge in this setting are lacking. Very recently RAS wild type status on circulating tumor DNA (ct-DNA) at the time of rechallenge along with already known clinical criteria emerged as a potential watershed for this strategy. In the present study we explored liquid biopsy-driven anti-EGFR rechallenge strategy in the clinical practice for patients with metastatic colorectal cancer. Methods: Ct-DNA from RAS and BRAF wild type metastatic CRC patients previously treated with an anti-EGFR containing therapy was analyzed for RAS/BRAF mutations with the aim to evaluate the rechallenge strategy with anti-EGFR. The ct-DNA was analyzed for RAS-BRAF mutations using pyro-sequencing (PyroMark Q24 MDx Workstation) and nucleotide sequencing (Genetic Analyzer ABI3130) assay...

BackgroundInnovative cancer immunotherapy approaches aim at combining immune checkpoint inhibitor... more BackgroundInnovative cancer immunotherapy approaches aim at combining immune checkpoint inhibitors with other immunomodulatory agents. Epigenetic regulators can control immune-related genes, therefore targeting them with specific inhibitors may be a potential way forward. Here we identified immune-related signatures induced by four classes of epigenetic drugs in human melanoma cells to define the most promising agent and to understand its biological activity in-vitro, in-vivo and in clinical samples.MethodsHuman melanoma cell lines were characterized for mutational and differentiation profile and treated with inhibitors of DNA methyltransferases (guadecitabine), histone deacetylases (givinostat), bromodomain and extraterminal domain proteins (JQ1 and OTX-015) and enhancer of zeste homolog 2 (GSK126). Drug-specific gene signatures were identified by Clariom S and Nanostring platforms. Modulation of 14 proteins was determined by quantitative western blot. Ingenuity Pathway Analysis (I...

Additional file 4. List of exonic genetic variants called by MiSeq™ Illumina Variant interpreter ... more Additional file 4. List of exonic genetic variants called by MiSeq™ Illumina Variant interpreter for the eleven tumor samples. All variants are annotated with the gene ID and locus RefSeq, and the mutation nomenclature is based on the convention recommended by the Human Genome Variation Society ( http://www.hgvs.org/mutnomen/ ) other than the variant allele and the nature of the allele call (heterozygous or homozygous). Frequency data indicate the percentage of the variant allele detected by Illumina. Moreover, they are annotated for dbSNP (rs number) or COSMIC v86 database, together with FATHMM score. The FATHMM is a functional score for individual mutations from FATHMM-MKL are in the form of a single p-value, ranging from 0 to 1. Scores above 0.5 are deleterious, but in order to highlight the most significant data in COSMIC, only scores ≥0.7 are classified as 'Pathogenic' whereas mutations are classed as 'Neutral' if the score is ≤0.5 [47]. The "Effect" c...

Additional file 1: Table S1. (A) The 750 somatic non-synonymous variants found in discovery cohor... more Additional file 1: Table S1. (A) The 750 somatic non-synonymous variants found in discovery cohort, in detail. In bold, variants classified as pathogenic/likely pathogenic mutations. (B) The 79 somatic non-synonymous variants found in validation cohort, in detail. In bold, variants classified as pathogenic/likely pathogenic mutations.

International Journal of Molecular Sciences, 2021

Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat ... more Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and its analogs have shown good anticancer properties and are being considered for use in combination with or sequence to recent therapies to improve patient outcomes. Our group previously published the synthesis and anticancer activity characterization of a novel curcumin-related compound against melanoma and neuroblastoma cells (D6). Here, two hydroxylated biphenyl compounds—namely, compounds 11 and 12—were selected among a small collection of previously screened C2-symmetric hydroxylated biphenyls structurally related to D6 and curcumin, showing the best antitumor potentiality against melanoma cells (IC50 values of 1.7 ± 0.5 μM for 11 and 2.0 ± 0.7 μM for 12) and no toxicity of normal fibroblasts up to 32 µM. Their anti...

BMC Pulmonary Medicine, 2022

Background Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. T... more Background Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations. Methods A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of low-frequency EGFR-T790M mutated alleles at baseline). Results The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18–21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs) a...

ChemMedChem, 2021

A small collection of C2‐symmetric hydroxylated biphenyl derivatives featuring an α,β‐unsaturated... more A small collection of C2‐symmetric hydroxylated biphenyl derivatives featuring an α,β‐unsaturated ketone as a lead structure was prepared, and the capacity of these compounds to act as antiproliferative agents against four human malignant melanoma cell lines was assayed. The prodrug approach was applied in order to improve the delivery of compounds into the cell by modulation of the phenolic hydroxy protecting group. The hydroxylated biphenyl structure bearing an α,β‐unsaturated ketone and a phenolic‐O‐prenylated chain was found to facilitate the delivery of the molecule and interactions with biological targets. Four compounds showed antiproliferative activity resulting in IC50 values in the range of 1.2 to 2.8 μM.

Annals of Oncology, 2021

Background: Female sex is reported to be associated with poor prognosis in hypertrophic cardiomyo... more Background: Female sex is reported to be associated with poor prognosis in hypertrophic cardiomyopathy (HCM). The plasma B-type natriuretic peptide (BNP) concentration is a prognostic predictor in HCM. However, the effect of sex on BNP concentrations remains unclear among HCM patients. Methods and Results: Patient records in the Clinical Personal Records of HCM national database of the Japanese Ministry of Health, Labour and Welfare from 2009 to 2014 were analyzed. Of 3,570 HCM patients, 611 in whom BNP concentrations were assessed at both baseline and the 2-year follow-up were included in this analysis. The mean age was 60.4 years and 254 (41.6%) patients were female. Median (interquartile range) BNP concentrations were higher in females than males at both baseline (320.3 [159.0-583.1] vs. 182.8 [86.1-363.9] pg/mL; P<0.001) and the 2-year follow-up (299.2 [147.0-535.3] vs. 161.0 [76.2-310.0] pg/mL; P<0.001). Female sex was associated with higher natural log-transformed BNP at the 2-year follow-up regardless of clinical characteristics, including echocardiographic findings and BNP concentrations at baseline (coefficient 0.31; 95% confidence interval 0.13-0.48; P<0.001). Cubic spline analysis showed that, among patients with high BNP concentrations at baseline, females had higher BNP concentrations at the 2-year follow-up than males. Conclusions: In HCM, female sex was associated with higher BNP concentrations than male sex, independent of clinical characteristics, including BNP concentrations at baseline.

Molecular Cancer Therapeutics, 2009

Sharing the common neuroectodermal origin, Malignant Melanoma (MM) and Neuroblastoma (NB) are tum... more Sharing the common neuroectodermal origin, Malignant Melanoma (MM) and Neuroblastoma (NB) are tumors widely diffused among adult and children, respectively. Despite the current advances in treatment options, clinical prognosis of aggressive neuroectodermal cancers remains dismal. Chemotherapeutics currently in use are still unsatisfactory, therefore the search for novel therapies for such tumors is warranted. Curcumin, main component of curry spice, is one of the phytochemicals widely studied for its antioxidant, anti-inflammatory and anti-cancer properties. Moreover, it has been reported that curcumin exerts a good anti-proliferative activity on neuroectodermal tumor cells by inducing apoptosis. Recently, we have synthetized and tested in vitro various curcumin related compounds in order to select new antitumor agents displaying stronger and selective growth inhibition activity on both MM and NB cells. In this work, we have demonstrated that a new curcumin-related biphenyl compound...

European Journal of Cancer, 2001

Cancer Research, 2012

Malignant melanoma (MM) is one of the most aggressive cancers that affect humans. It is the most ... more Malignant melanoma (MM) is one of the most aggressive cancers that affect humans. It is the most common and fatal skin cancer, with an incidence that is critically increasing in Western populations (15 times in the last 40 years) and for which, in the advanced stages, there is no effective therapy. The search for new compounds able to control it is therefore essential. The hydroxylated biphenyl compound (3E,3′E)-4,4′-(5,5′,6,6′-tetramethoxy-[1,1′-biphenyl]-3,3′-diyl)bis(but-3-en-2-one), namely D6, a structural analogue of curcumin, showed a strong antitumor activity on MM cells both in vitro and in vivo, as we have recently described [1]. The mechanisms of action of this compound are not clear yet, but it inhibits cancer cells growth by inducing apoptosis without affecting normal fibroblasts growth. Firstly we investigated the ability of D6 to enter cells by Liquid Chromatography-Mass Spectrometry (LC-MS) analysis. The LC-MS data showed a quick cellular uptake of D6 with a maximum p...

Annals of Oncology, 2002

The Sardinian population is genetically homogeneous and could be useful in understanding better t... more The Sardinian population is genetically homogeneous and could be useful in understanding better the genetics of a complex disease like breast cancer (BC). Using a screening assay based on a combination of single-strand conformation polymorphism, denaturing high-performance liquid chromatography and sequence analysis, 47 Sardinian families with three or more BC cases were screened for germline mutations in BRCA1 and BRCA2 genes. Three BRCA1/2 germline sequence variants were identified. While BRCA2-Ile3412Val is a missense variant with unknown functional significance, BRCA2-8765delAG and BRCA1-Lys505ter are two deleterious mutations (due to their predicted effects on protein truncation), which were found in seven families (15%). BRCA2-8765delAG was found in six of eight (75%) BRCA1/2-positive families and seven of 501 (1.4%) unselected and consecutively collected BC patients. Prevalence of BRCA1/2 mutations in BC families was significantly correlated with the total number of female BCs (P &amp;amp;amp;amp;amp;lt;0.01) and increased by the presence of (i) at least one case of ovarian or male BC, or (ii) three generations affected, or (iii) bilateral BC. Identification of such features should address BC patients and their families to genetic counseling and BRCA1/2 mutational analysis. In addition, this is the first report of a detailed BRCA1/2 mutation screening in Sardinia, having immediate implications for the clinical management of BC families.

Proceedings of the National Academy of Sciences, 1995

TFC5, the unique and essential gene encoding the B" component of the Saccharomyces cerevisia... more TFC5, the unique and essential gene encoding the B" component of the Saccharomyces cerevisiae RNA polymerase III transcription factor (TF)IIIB has been cloned. It encodes a 594-amino acid protein (67,688 Da). Escherichia coli-produced B" has been used to reconstitute entirely recombinant TFIIIB that is fully functional for TFIIIC-directed, as well as TATA box-dependent, DNA binding and transcription. The DNase I footprints of entirely recombinant TFIIIB, composed of B", the 67-kDa Brf, and TATA box-binding protein, and TFIIIB reconstituted with natural B" are indistinguishable. A truncated form of B" lacking 39 N-terminal and 107 C-terminal amino acids is also functional for transcription.

Metallomics, 2019

Malignant melanoma (MM) is the most fatal skin cancer, whose incidence has critically increased i... more Malignant melanoma (MM) is the most fatal skin cancer, whose incidence has critically increased in the last decades. Recent molecular therapies are giving excellent results in the remission of melanoma but often they induce drug resistance in patients limiting their therapeutic efficacy. The search for new compounds able to overcome drug resistance is therefore essential. Vanadium has recently been cited for its anticancer properties against several tumors, but only a few data regard its effect against MM. In a previous work we demonstrated the anticancer activity of four different vanadium species towards MM cell lines. The inorganic anion vanadate(v) (VN) and the oxidovanadium(iv) complex [VO(dhp)2] (VS2), where dhp is 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate, showed IC50 values of 4.7 and 2.6 μM, respectively, against the A375 MM cell line, causing apoptosis and cell cycle arrest. Here we demonstrate the involvement of Reactive Oxygen Species (ROS) production in the pro-apoptoti...

Journal of Clinical Medicine

Malignant melanoma (MM) is one of the deadliest skin cancers. BRAF mutation status plays a predom... more Malignant melanoma (MM) is one of the deadliest skin cancers. BRAF mutation status plays a predominant role in the management of MM patients. The aim of this study was to compare BRAF mutational testing performed by conventional nucleotide sequencing approaches with either real-time polymerase chain reaction (rtPCR) or next-generation sequencing (NGS) assays in a real-life, hospital-based series of advanced MM patients. Consecutive patients with AJCC (American Joint Committee on Cancer) stage IIIC and IV MM from Sardinia, Italy, who were referred for molecular testing, were enrolled into the study. Initial screening was performed to assess the mutational status of the BRAF and NRAS genes, using the conventional methodologies recognized by the nationwide guidelines, at the time of the molecular classification, required by clinicians: at the beginning, Sanger-based sequencing (SS) and, after, pyrosequencing. The present study was then focused on BRAF mutation detecting approaches only...