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  • 1
    Online Resource
    Online Resource
    No indications for HPV involvement in the hypertrophic skin lesions of a Darier disease case without ATP2A2 gene mutations
    Wiley ; 2009
    In:  Journal of Cutaneous Pathology Vol. 36, No. 9 ( 2009-09), p. 1005-1009
    Details
    In: Journal of Cutaneous Pathology, Wiley, Vol. 36, No. 9 ( 2009-09), p. 1005-1009
    Abstract: Darier disease (DD) is a relatively common genodermatosis characterized by impaired differentiation and abnormal cell‐to‐cell adhesion. Haploinsufficiency of the ATP2A2 gene product, sarco/endoplasmic reticulum Ca 2+ ATPase isoform 2 (SERCA2), is the underlying cause of most cases. Although DD may have a papillomatous appearance, few and controversial results have been reported about the role of human papillomavirus (HPV) in this disease. The aim of this study was to determine a possible correlation between development of hypertrophic lesions in DD and infection by HPV. We report the case of an 84‐year‐old woman with a hypertrophic DD variant that has been successfully treated with oral retinoids. HPV analysis for a broad spectrum of cutaneous and mucocutaneous genotypes was performed on surgical specimens obtained from the cutaneous lesions and snap‐frozen plucked eyebrows. Genetic analysis of the ATP2A2 gene did not detect any mutations. Epidermal expression of SERCA2b was shown by immunohistochemistry. We describe a patient with DD lacking mutations of the ATP2A2 gene, but with reduced SERCA2b expression in the epidermal keratinocytes. The results obtained by polymerase chain reaction (PCR) genotyping, quantitative real‐time PCR, and in situ hybridization indicate that HPV replication was very low and suggest no direct role of the virus in the development of the disease.
    Type of Medium: Online Resource
    ISSN: 0303-6987 , 1600-0560
    URL: Issue
    URL: Article
    DOI: 10.1111/cup.2009.36.issue-9
    DOI: 10.1111/j.1600-0560.2009.01182.x
    Language: English
    Publisher: Wiley
    Publication Date: 2009
    detail.hit.zdb_id: 2018100-0
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  • 2
    Online Resource
    Online Resource
    Differential therapeutic effects of PARP and ATR inhibition combined with radiotherapy in the treatment of subcutaneous versus orthotopic lung tumour models
    Springer Science and Business Media LLC ; 2020
    In:  British Journal of Cancer Vol. 123, No. 5 ( 2020-09-01), p. 762-771
    Details
    In: British Journal of Cancer, Springer Science and Business Media LLC, Vol. 123, No. 5 ( 2020-09-01), p. 762-771
    Abstract: Subcutaneous mouse tumour models are widely used for the screening of novel antitumour treatments, although these models are poor surrogate models of human cancers. Methods We compared the antitumour efficacy of the combination of ionising radiation (IR) with two DNA damage response inhibitors, the PARP inhibitor olaparib and the ATR inhibitor AZD6738 (ceralasertib), in subcutaneous versus orthotopic cancer models. Results Olaparib delayed the growth of irradiated Lewis lung carcinoma (LL2) subcutaneous tumours, in agreement with previous reports in human cell lines. However, the olaparib plus IR combination showed a very narrow therapeutic window against LL2 lung orthotopic tumours, with nearly no additional antitumour effect compared with that of IR alone, and tolerability issues emerged at high doses. The addition of AZD6738 greatly enhanced the efficacy of the olaparib plus IR combination treatment against subcutaneous but not orthotopic LL2 tumours. Moreover, olaparib plus AZD6738 administration concomitant with IR even worsened the response to radiation of head and neck orthotopic tumours and induced mucositis. Conclusions These major differences in the responses to treatments between subcutaneous and orthotopic models highlight the importance of using more pathologically relevant models, such as syngeneic orthotopic models, to determine the most appropriate therapeutic approaches for translation to the clinic.
    Type of Medium: Online Resource
    ISSN: 0007-0920 , 1532-1827
    URL: Article
    DOI: 10.1038/s41416-020-0931-6
    RVK:
    XA 33500
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2002452-6
    detail.hit.zdb_id: 80075-2
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  • 3
    Online Resource
    Online Resource
    The combination of the antiviral agent cidofovir and anti-EGFR antibody cetuximab exerts an antiproliferative effect on HPV-positive cervical cancer cell lines’ in-vitro and in-vivo xenografts
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Anti-Cancer Drugs Vol. 24, No. 6 ( 2013-07), p. 599-608
    Details
    In: Anti-Cancer Drugs, Ovid Technologies (Wolters Kluwer Health), Vol. 24, No. 6 ( 2013-07), p. 599-608
    Type of Medium: Online Resource
    ISSN: 0959-4973
    URL: Article
    DOI: 10.1097/CAD.0b013e3283612a71
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2025803-3
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  • 4
    Online Resource
    Online Resource
    A novel autoantigen to differentiate limited cutaneous systemic sclerosis from diffuse cutaneous systemic sclerosis: The interferon‐inducible gene IFI16
    Wiley ; 2006
    In:  Arthritis & Rheumatism Vol. 54, No. 12 ( 2006-12), p. 3939-3944
    Details
    In: Arthritis & Rheumatism, Wiley, Vol. 54, No. 12 ( 2006-12), p. 3939-3944
    Abstract: To investigate the presence and clinical significance of autoantibodies against the interferon‐inducible gene IFI16 in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and other autoimmune diseases. Methods Immunohistochemical analysis was used to evaluate the expression of IFI16 in skin biopsy specimens obtained from patients with SSc and patients with SLE. Levels of antibodies against IFI16 in sera from 82 patients with SSc and 100 patients with SLE were determined by enzyme‐linked immunosorbent assay. Other autoimmune diseases such as primary Sjögren's syndrome (SS), rheumatoid arthritis (RA), chronic urticaria, and hepatitis C virus (HCV) infection were also examined. Results Expression of IFI16 was greatly increased and was ubiquitous in all layers of the epidermis and in the dermal inflammatory infiltrates of lesional skin from both patients with SLE and patients with SSc. Patients with SLE, those with primary SS, and those with SSc exhibited significantly higher anti‐IFI16 IgG antibody levels compared with normal controls (for SLE, P 〈 0.002; for primary SS, P 〈 0.001; for SSc, P 〈 0.0005). Anti‐IFI16 titers above the ninety‐fifth percentile for control subjects were observed in 26% of the patients with SLE, 50% of those with primary SS, and 21% of those with SSc (28% of patients with limited cutaneous SSc [lcSSc] versus 4% of patients with diffuse cutaneous SSc [dcSSc] ). In contrast, the prevalence of anti‐IFI16 was 4% in patients with RA, 5% in those with chronic urticaria, and 13% in those with HCV infection. Conclusion The results of this study provide evidence that an IFN‐inducible gene, IFI16, may be involved in the pathophysiologic mechanisms of connective tissue disorders such as SSc. Moreover, a strict correlation with lcSSc was also demonstrated, thus providing a novel tool in the differential diagnosis of lcSSc from dcSSc.
    Type of Medium: Online Resource
    ISSN: 0004-3591 , 1529-0131
    URL: Issue
    URL: Article
    DOI: 10.1002/art.v54:12
    DOI: 10.1002/art.22266
    RVK:
    XA 10000
    RVK:
    XA 30325
    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 2014367-9
    detail.hit.zdb_id: 2754614-7
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  • 5
    Online Resource
    Online Resource
    Stepwise Assembled Photoactive Films Containing Donor-Linked Fullerenes
    Wiley ; 2000
    In:  Angewandte Chemie Vol. 39, No. 21 ( 2000-11-03), p. 3905-3909
    Details
    In: Angewandte Chemie, Wiley, Vol. 39, No. 21 ( 2000-11-03), p. 3905-3909
    Type of Medium: Online Resource
    ISSN: 1433-7851 , 1521-3773
    URL: Issue
    URL: Journal
    URL: Article
    DOI: 10.1002/1521-3773(20001103)39:21〈〉1.0.CO;2-Z
    DOI: 10.1002/(ISSN)1521-3773
    DOI: 10.1002/1521-3773(20001103)39:21〈3905::AID-ANIE3905〉3.0.CO;2-Q
    RVK:
    VA 2100
    Language: English
    Publisher: Wiley
    Publication Date: 2000
    detail.hit.zdb_id: 2011836-3
    detail.hit.zdb_id: 123227-7
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  • 6
    Online Resource
    Online Resource
    Radiotherapy–immunotherapy combinations – perspectives and challenges
    Wiley ; 2020
    In:  Molecular Oncology Vol. 14, No. 7 ( 2020-07), p. 1529-1537
    Details
    In: Molecular Oncology, Wiley, Vol. 14, No. 7 ( 2020-07), p. 1529-1537
    Abstract: Ionizing radiation has historically been used to treat cancer by killing tumour cells, in particular by inducing DNA damage. This view of radiotherapy (RT) as a simple cytotoxic agent has dramatically changed in recent years, and it is now widely accepted that RT can deeply reshape the tumour environment by modulating the immune response. Such evidence gives a strong rationale for the use of immunomodulators to boost the therapeutic value of RT, introducing the era of ‘immunoradiotherapy’. The increasing amount of preclinical and clinical data concerning the combination of RT with immunomodulators, in particular with immune checkpoint inhibitors such as anti‐PD‐1/PD‐L1 and anti‐CTLA4, reflects the interest of the scientific and medical community concerning immunoradiotherapy. The expectations are enormous since the rationale for performing such combinations is strong, with the possibility to use a local treatment such as RT to amplify a systemic antitumour response, as illustrated by the case of the abscopal effect. Nevertheless, several points remain to be addressed such as the need to find biomarkers to identify patients who will benefit from immunoradiotherapy, the identification of the best sequences/schedules for combination with immunomodulators and mechanisms to overcome resistance. Additionally, the effects of immunoradiotherapy on healthy tissues and related toxicity remain largely unexplored. To answer these critical questions and make immunoradiotherapy keep its promising qualities, large efforts are needed from both the pharmaceutical industry and academic/governmental research. Moreover, because of the work of both these entities, the arsenal of available immunomodulators is quickly expanding, thus opening the field to increasing combinations with RT. We thus forecast that the field of immunoradiotherapy will further expand in the coming years, and it needs to be supported by appropriate investment plans.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    URL: Issue
    URL: Article
    DOI: 10.1002/mol2.v14.7
    DOI: 10.1002/1878-0261.12658
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2322586-5
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  • 7
    Online Resource
    Online Resource
    A Procedure for the Quantitative Comparison of Rainfall and DInSAR-Based Surface Displacement Time Series in Slow-Moving Landslides: A Case Study in Southern Italy
    MDPI AG ; 2023
    In:  Remote Sensing Vol. 15, No. 2 ( 2023-01-05), p. 320-
    Details
    In: Remote Sensing, MDPI AG, Vol. 15, No. 2 ( 2023-01-05), p. 320-
    Abstract: Earth observation data are useful to analyze the impact of climate-related variables on geomorphological processes. This work aims at evaluating the impact of rainfall on slow-moving landslides, by means of a quantitative procedure for identifying satellite-based displacement clusters, comparing them with rainfall series, and applying statistical tests to evaluate their relationships at the regional scale. The chosen study area is the Basento catchment in the Basilicata region (southern Italy). Rainfall series are gathered from rain gauges and are analyzed to evaluate the presence of temporal trends. Ground displacements are obtained by applying the P-SBAS (Parallel Small BAseline Subset) to three datasets of Sentinel-1 images: T146 ascending orbit, and T51 and T124 descending orbits, for the period 2015–2020. The displacement series of the pixels located in areas mapped as landslides by the Italian Landslide Inventory and sited within rain gauge influence regions (defined as 10 km circular buffers) are studied. Those displacement series are analyzed and compared to the rainfall series to search for correlations, by employing statistical and non-parametric tests. In particular, two landslides are selected and investigated in detail. Significant results were obtained for the T124 descending orbit for both landslides, for a 3-day cumulative rainfall and a 7-day delay of the slope response. Challenges in the whole procedure are highlighted and possible solutions to overcome the raised problems are proposed. Given the replicability of the proposed quantitative procedure it might be applied to any study area.
    Type of Medium: Online Resource
    ISSN: 2072-4292
    URL: Article
    DOI: 10.3390/rs15020320
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2513863-7
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  • 8
    Online Resource
    Online Resource
    Sentinel-1 SAR Amplitude Imagery for Rapid Landslide Detection
    MDPI AG ; 2019
    In:  Remote Sensing Vol. 11, No. 7 ( 2019-03-29), p. 760-
    Details
    In: Remote Sensing, MDPI AG, Vol. 11, No. 7 ( 2019-03-29), p. 760-
    Abstract: Despite landslides impact the society worldwide every day, landslide information is inhomogeneous and lacking. When landslides occur in remote areas or where the availability of optical images is rare due to cloud persistence, they might remain unknown, or unnoticed for long time, preventing studies and hampering civil protection operations. The unprecedented availability of SAR C-band images provided by the Sentinel-1 constellation offers the opportunity to propose new solutions to detect landslides events. In this work, we perform a systematic assessment of Sentinel-1 SAR C-band images acquired before and after known events. We present the results of a pilot study on 32 worldwide cases of rapid landslides entailing different types, sizes, slope expositions, as well as pre-existing land cover, triggering factors and climatic regimes. Results show that in about eighty-four percent of the cases, changes caused by landslides on SAR amplitudes are unambiguous, whereas only in about thirteen percent of the cases there is no evidence. On the other hand, the signal does not allow for a systematic use to produce inventories because only in 8 cases, a delineation of the landslide borders (i.e., mapping) can be manually attempted. In a few cases, cascade multi-hazard (e.g., floods caused by landslides) and evidences of extreme triggering factors (e.g., strong earthquakes or very rapid snow melting) were detected. The method promises to increase the availability of information on landslides at different spatial and temporal scales with benefits for event magnitude assessment during weather-related emergencies, model tuning, and landslide forecast model validation, in particular when accurate mapping is not required.
    Type of Medium: Online Resource
    ISSN: 2072-4292
    URL: Article
    DOI: 10.3390/rs11070760
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2513863-7
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  • 9
    Online Resource
    Online Resource
    Dual oxidase 1 limits the IFNγ-associated antitumor effect of macrophages
    BMJ ; 2020
    In:  Journal for ImmunoTherapy of Cancer Vol. 8, No. 1 ( 2020-06), p. e000622-
    Details
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 8, No. 1 ( 2020-06), p. e000622-
    Abstract: Macrophages play pivotal roles in tumor progression and the response to anticancer therapies, including radiotherapy (RT). Dual oxidase (DUOX) 1 is a transmembrane enzyme that plays a critical role in oxidant generation. Methods Since we found DUOX1 expression in macrophages from human lung samples exposed to ionizing radiation, we aimed to assess the involvement of DUOX1 in macrophage activation and the role of these macrophages in tumor development. Results Using Duox1 −/− mice, we demonstrated that the lack of DUOX1 in proinflammatory macrophages improved the antitumor effect of these cells. Furthermore, intratumoral injection of Duox1 −/− proinflammatory macrophages significantly enhanced the antitumor effect of RT. Mechanistically, DUOX1 deficiency increased the production of proinflammatory cytokines (IFNγ, CXCL9, CCL3 and TNFα) by activated macrophages in vitro and the expression of major histocompatibility complex class II in the membranes of macrophages. We also demonstrated that DUOX1 was involved in the phagocytotic function of macrophages in vitro and in vivo . The antitumor effect of Duox1 −/− macrophages was associated with a significant increase in IFNγ production by both lymphoid and myeloid immune cells. Conclusions Our data indicate that DUOX1 is a new target for macrophage reprogramming and suggest that DUOX1 inhibition in macrophages combined with RT is a new therapeutic strategy for the management of cancers.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    URL: Article
    DOI: 10.1136/jitc-2020-000622
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2719863-7
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  • 10
    Online Resource
    Online Resource
    Altered expression of UVB-induced cytokines in human papillomavirus-immortalized epithelial cells
    Microbiology Society ; 2008
    In:  Journal of General Virology Vol. 89, No. 10 ( 2008-10-01), p. 2461-2466
    Details
    In: Journal of General Virology, Microbiology Society, Vol. 89, No. 10 ( 2008-10-01), p. 2461-2466
    Abstract: Keratinocytes can be induced to produce cytokines by exogenous stimuli, such as UVB, and dysregulation of this production has been described in various skin diseases, including cancer. In this study, we compared the effect of UVB on the secretion of several cytokines involved in inflammation by human keratinocytes immortalized or not with human papillomavirus (HPV)16 or HPV38 at the mRNA and protein levels. We show that expression of the HPV E6/E7 oncoproteins influences not only the basal cytokine secretion profile of keratinocytes, but also its modulation upon UVB irradiation. In particular, UVB upregulates interleukin (IL)-6, IL-8 and transforming growth factor (TGF)- β in HPV-immortalized cells to a higher extent than in control keratinocytes. Moreover, expression of other pro-inflammatory molecules such as S100A8/9 and interferon (IFN)- κ was downregulated in HPV-immortalized cells. These data support the functional similarity between HPV16 and 38, and suggest an active role of these viruses in modulation of the inflammatory process.
    Type of Medium: Online Resource
    ISSN: 0022-1317 , 1465-2099
    URL: Article
    DOI: 10.1099/vir.0.83586-0
    RVK:
    XA 53770
    RVK:
    WA 15000
    Language: English
    Publisher: Microbiology Society
    Publication Date: 2008
    detail.hit.zdb_id: 2007065-2
    SSG: 12
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