Papers by Rebecca Senetta
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Il Pensiero Scientifico Editore, 2018
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Nature communications, May 31, 2017
Stromal content heavily impacts the transcriptional classification of colorectal cancer (CRC), wi... more Stromal content heavily impacts the transcriptional classification of colorectal cancer (CRC), with clinical and biological implications. Lineage-dependent stromal transcriptional components could therefore dominate over more subtle expression traits inherent to cancer cells. Since in patient-derived xenografts (PDXs) stromal cells of the human tumour are substituted by murine counterparts, here we deploy human-specific expression profiling of CRC PDXs to assess cancer-cell intrinsic transcriptional features. Through this approach, we identify five CRC intrinsic subtypes (CRIS) endowed with distinctive molecular, functional and phenotypic peculiarities: (i) CRIS-A: mucinous, glycolytic, enriched for microsatellite instability or KRAS mutations; (ii) CRIS-B: TGF-β pathway activity, epithelial-mesenchymal transition, poor prognosis; (iii) CRIS-C: elevated EGFR signalling, sensitivity to EGFR inhibitors; (iv) CRIS-D: WNT activation, IGF2 gene overexpression and amplification; and (v) C...
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Neuro-Oncology, 2017
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European Respiratory Journal, 2015
The TK receptor MET orchestates 9invasive growth9, a genetic program driving the metastatic proce... more The TK receptor MET orchestates 9invasive growth9, a genetic program driving the metastatic process. Deregulation of MET signaling pathway occurs via different mechanisms: protein overexpression, gene amplification, mutations or rearrangements. While the role of MET mutations in NSCLC is not yet fully understood, MET amplification drives cell survival and MET-amplified cells are sensitive to MET inhibition. This study aimed to evaluate the occurrence of genetic lesions affecting MET locus on 7q31.1 in primary e metastatic NSCLCs and to decipher a distribution pattern based on disease stage and outcome. A cohort of 69 cases of NSCLC and their matched brain metastases were firstly screened for the expression MET by IHC. Genomic tumor DNA was then sequenced to identify either MET somatic mutations, whereas gene copy number was carried on through FISH analysis on FFPE slides. The results found were then matched with corresponding clinical data. We demonstrate that MET locus was mainly overexpressed in NSCLC metastatic sites. MET somatic mutations were found in 5 of the 54 cases (9%) analysed : in two cases the same mutation was present in both primary and metastatic tissue, whereas in the remaining three mutation affected only brain metastasis. MET amplification was associated to a worst outcome and a poor response to chemotherapy. MET activation was related to tumor radioresistance. (p
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Gastrointestinal Endoscopy, 2014
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Cancer Research, 2021
Cancers of Unknown Primary (CUPs), featuring metastatic dissemination in the absence of a primary... more Cancers of Unknown Primary (CUPs), featuring metastatic dissemination in the absence of a primary tumor, anatomically or histologically recognizable through a standardized work-up, are a fatal disease and still a biological enigma. Here, we propose CUPs as a distinct, yet unrecognized, pathological entity originating from stem-like cells endowed with unique properties, irrespective of their different genetic backgrounds. These cells were isolated and long-term propagated in vitro in highly stringent conditions as ‘agnospheres', and serially transplanted in vivo, displaying an extremely high tumorigenic potential and reproducing the undifferentiated histology of the original tumors. Early after subcutaneous engraftment, agnospheres recapitulated the CUP clinical presentation, as they spontaneously and quickly disseminated, establishing widespread metastases and retracing the whole metastatic cascade. Agnospheres invariably displayed cell-autonomous proliferation and self-renewal,...
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Journal of Clinical Oncology
9574 Background: The aim of neo-adjuvant therapy in locally advanced or oligometastatic melanoma ... more 9574 Background: The aim of neo-adjuvant therapy in locally advanced or oligometastatic melanoma is to facilitate radical resection, improve outcomes and undertake research to identify biomarkers of response and resistance. The optimal schedule to balance efficacy vs toxicity in dual PD1/CTLA4 blockade regimens remains a matter of debate. We initiated an open- label, single arm study to investigate the Nivo 3/ Ipi 1 schedule as primary treatment of locally advanced or oligometastatic melanoma patients (pts). Methods: Treatment schedule consists in 4 neoadjuvant cycles of Ipilimumab 1 mg/kg and Nivolumab 3 mg/kg every 3 weeks, followed by surgery and adjuvant Nivolumab 480 mg every 4 weeks for 6 cycles. Primary objective is pathological complete remission (pCR) rate, according to Neoadjuvant Melanoma Consortium criteria. Secondary objectives are: safety, feasibility and efficacy; QoL; identification of molecular and immunological biomarkers of response and resistance (somatic genetic...
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International Journal of Molecular Sciences
Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical featur... more Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical features and are now regarded as an intermediate category of melanocytic tumors with uncertain malignant potential. Activating NTRK1/NTRK3 fusions elicit oncogenic events in Spitz lesions and are targetable with kinase inhibitors. However, their prevalence among ASTs and the optimal approach for their detection is yet to be determined. A series of 180 ASTs were screened with pan-TRK immunohistochemistry and the presence of NTRK fusions was confirmed using FISH, two different RNA-based NGS panels for solid tumors, and a specific real time RT-PCR panel. Overall, 26 ASTs showed pan-TRK immunostaining. NTRK1 fusions were detected in 15 of these cases showing cytoplasmic immunoreaction, whereas NTRK3 was detected in one case showing nuclear immunoreaction. Molecular tests resulted all positive in only two ASTs (included the NTRK3 translocated), RNA-based NGS and real time RT-PCR were both positive ...
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Additional file 2: Table S2. Histopathological features of the upgraded lesions.
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Italian Journal of Dermatology and Venereology, 2021
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Cells, 2022
Sézary syndrome is a rare subtype of cutaneous T-cell lymphoma characterized by erythroderma, per... more Sézary syndrome is a rare subtype of cutaneous T-cell lymphoma characterized by erythroderma, peripheral lymphadenopathies, and circulating atypical cerebriform T-cells. To date, no definite staging system has been developed for these patients. In this retrospective analysis of the archive of the Dermatological Clinic of the University of Turin, Italy, erythrodermic SS patients were classified according to clinical records and photographs into three main presentations: erythematous, infiltrated, or melanodermic. The pattern of erythroderma was found to be associated with disease outcome, as better survivals were recorded in patients with erythematous and infiltrative erythroderma. Patients in the melanodermic group, though less represented in our investigation, seemed to show a worse trend in survival. According to this preliminary evidence, a new prognostic classification, with a revised score specific for Sézary syndrome patients, can be proposed to usefully integrate the current ...
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Annals of Oncology, 2020
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Journal of Investigative Dermatology, 2020
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International Journal of Molecular Sciences, 2019
Background: Dp71 is the most abundant dystrophin (DMD) gene product in the nervous system. Mutati... more Background: Dp71 is the most abundant dystrophin (DMD) gene product in the nervous system. Mutation in the Dp71 coding region is associated with cognitive disturbances in Duchenne muscular dystrophy (DMD) patients, but the function of dystrophin Dp71 in tumor progression remains to be established. This study investigated Dp71 expression in glioblastoma, the most common and aggressive primary tumor of the central nervous system (CNS). Methods: Dp71 expression was analyzed by immunofluorescence, immunohistochemistry, RT-PCR, and immunoblotting in glioblastoma cell lines and cells isolated from human glioblastoma multiforme (GBM) bioptic specimens. Results: Dp71 isoform was expressed in normal human astrocytes (NHA) cell lines and decreased in glioblastoma cell lines and cells isolated from human glioblastoma multiforme bioptic specimens. Moreover, Dp71 was localized in the nucleus in normal cells, while it was localized into the cytoplasm of glioblastoma cells organized in clusters. W...
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Pathology, 2019
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Tumor Biology, 2017
Despite the consolidated clinico-pathological correlates of Caveolin 1 expression in non–small ce... more Despite the consolidated clinico-pathological correlates of Caveolin 1 expression in non–small cell lung cancer, the available data on the role of Caveolin 1 in relation to proliferation, migration, and metastasis in lung adenocarcinoma cells is still scant. Here, we aimed to confirm whether Caveolin 1 may act as a promoter of cell growth in human lung adenocarcinoma using in vitro and in vivo models, supported by a survival analysis of Caveolin 1 expression in a series of 116 primary lung adenocarcinomas. The silencing of endogenous Caveolin 1 expression in H522 lung adenocarcinoma cells through stable shRNA transfection significantly inhibited cellular proliferation in vitro and in vivo, in a lung adenocarcinoma xenograft mouse model. The bioluminescence imaging analysis revealed that tumors derived from Caveolin 1 shRNA-transfected cells grew slower than control xenografts. However, this difference progressively diminished over time and was definitively lost after 21 days. This w...
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Lung Cancer, 2017
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Oncotarget, Jan 9, 2017
With the aim of elucidating the relationship between Stat3 expression and tumor vessels abnormali... more With the aim of elucidating the relationship between Stat3 expression and tumor vessels abnormalities in the PCNLs, in this study we evaluated Stat3 and pStat3 expression by Real-time PCR and by immunohistochemistry in biopsy sections from PCNSL patients. Correlations of the expression levels with the presence of aberrant vessels were analyzed by confocal laser microscopy analysis, using FVIII as endothelial cell marker, CD133 and nestin as cancer stem cell (CSC) marker, CD20 as tumor cell marker, and Stat3. In addition, we investigated Stat3 mutations in lymphoma cells to clarify the role of the constitutive expression of Stat3 and of its phosphorylated forms. Results showed that in PCNSL, putative endothelial cells lining the vessels are heterogeneous, expressing FVIII/ pStat3/CD133 (presumably originally they are vascular progenitor cells), as well as FVIII/CD20/CD133 (presumably originally they are tumor cells). Finally, we detected a fraction of the FVIII+ endothelial cell that...
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Dermatology, 2016
Background: The new AJCC classification has highlighted some particular risk factors for squamous... more Background: The new AJCC classification has highlighted some particular risk factors for squamous cell carcinoma (SCC) relevant for prognosis. Incomplete excision is not infrequent in SCC. The aim of this study is to examine features that can predict an incomplete excision on the basis of the new AJCC classification and to review the literature on this topic. Materials and Methods: 81 SCC patients were included. All patients were submitted to excisional biopsy with a margin of at least 4 mm from the clinical edges as recommended. Histological characteristics of the lesions analysed were maximum diameter, grading, site, Breslow thickness, Clark level, deep tissue invasion (neural, bone, muscle), presence of ulceration and positivity of the margins. Results: The average Breslow thickness was 3.93 mm. Out of the 81 patients included, 14 showed involved margins. The 2 parameters that were implicated in predicting involvement of the margins in the multivariable model were Breslow thickne...
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Papers by Rebecca Senetta