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| 2. |
- Asim, M, et al.
(författare)
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Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1, s. 374-
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Tidskriftsartikel (refereegranskat)abstract
- Emerging data demonstrate homologous recombination (HR) defects in castration-resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here we demonstrate a direct requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT). Furthermore, upregulation of PARP activity is essential for the survival of prostate cancer cells and we demonstrate a synthetic lethality between ADT and PARP inhibition in vivo. Our data suggest that ADT can functionally impair HR prior to the development of castration resistance and that, this potentially could be exploited therapeutically using PARP inhibitors in combination with androgen-deprivation therapy upfront in advanced or high-risk prostate cancer.
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| 3. |
- Gao, RL, et al.
(författare)
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Nanogrid single-nucleus RNA sequencing reveals phenotypic diversity in breast cancer
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1, s. 228-
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Tidskriftsartikel (refereegranskat)abstract
- Single cell RNA sequencing has emerged as a powerful tool for resolving transcriptional diversity in tumors, but is limited by throughput, cost and the ability to process archival frozen tissue samples. Here we develop a high-throughput 3′ single-nucleus RNA sequencing approach that combines nanogrid technology, automated imaging, and cell selection to sequence up to ~1800 single nuclei in parallel. We compare the transcriptomes of 485 single nuclei to 424 single cells in a breast cancer cell line, which shows a high concordance (93.34%) in gene levels and abundance. We also analyze 416 nuclei from a frozen breast tumor sample and 380 nuclei from normal breast tissue. These data reveal heterogeneity in cancer cell phenotypes, including angiogenesis, proliferation, and stemness, and a minor subpopulation (19%) with many overexpressed cancer genes. Our studies demonstrate the utility of nanogrid single-nucleus RNA sequencing for studying the transcriptional programs of tumor nuclei in frozen archival tissue samples.
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| 4. |
- Garrone, O, et al.
(författare)
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Treating patients with cancer amidst the COVID-19 pandemic: experience of a regional hospital in the Piedmont region in northern Italy
- 2020
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Ingår i: Tumori. - : SAGE Publications. - 2038-2529. ; 106:5, s. 427-431
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Tidskriftsartikel (refereegranskat)abstract
- The coronavirus disease 2019 (COVID-19) pandemic is posing an unprecedented dilemma to oncologists worldwide, forcing them to decide whether to continue or suspend treatments in order to protect their most vulnerable patients from infection. After the first report from China, the outbreak spread rapidly worldwide. To, date no clear indications on how to treat patients with cancer with COVID-19 infection are available.Methods:We report data on 21 patients with cancer referred to a single medical oncology unit of a general hospital from mid-March to April 23, 2020.Results:Nine patients were on active cancer therapy during the infection and all stopped medical treatments. Overall 8 patients developed pneumonia and 6 patients died of COVID-19.Conclusion:The management of patients with cancer during the pandemic should be carefully balanced and discussed among oncologists and other key professionals involved in the treatment of this vulnerable group of patients, in order to balance the risk of treatment and the risk of infection.
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| 6. |
- Merlano, MC, et al.
(författare)
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Cytokine Profiling of End Stage Cancer Patients Treated with Immunotherapy
- 2021
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Ingår i: Vaccines. - : MDPI AG. - 2076-393X. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Published data suggest that immunotherapy plays a role even in patients with very advanced tumours. We investigated the immune profile of end-stage cancer patients treated with immunotherapy to identify changes induced by treatment. Breast, colon, renal and prostate cancer patients were eligible. Treatment consisted of metronomic cyclophosphamide, low-dose interleukin-2 (IL-2) and a single radiation shot. A panel of 16 cytokines was assessed using automated ELISA before treatment (T0), after radiation (RT; T1), at cycle 2 (T2) and at disease progression (TPD). Receiving operating characteristic (ROC) analysis was used to identify cytokine cut-off related to overall survival (OS). Principal component analysis (PCA) was used to identify the immune profile correlating better with OS and progression-free survival. Twenty-three patients were enrolled. High IL-2, low IL-8 and CCL-2 correlated with OS. The PCA identified a cluster of patients, with high IL-2, IL-12 and IFN-γ levels at T0 having longer PFS and OS. In all cohorts, IL-2 and IL-5 increased from T0 to T2; a higher CCL-4 level compared to T2 and a higher IL-8 level compared to T0 were found at TPD. The progressive increase of the IL-10 level during treatment negatively correlated with OS. Our data suggested that baseline cytokine levels may predict patients’ outcome and that the treatment may affect their kinetic even in end-stage patients. Cytokine profiling of end-stage patients might offer a tool for medical decisions (EUDRACT: 2016-000578-39).
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| 7. |
- Simonetti, M, et al.
(författare)
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COVseq is a cost-effective workflow for mass-scale SARS-CoV-2 genomic surveillance
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3903-
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Tidskriftsartikel (refereegranskat)abstract
- While mass-scale vaccination campaigns are ongoing worldwide, genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to monitor the emergence and global spread of viral variants of concern (VOC). Here, we present a streamlined workflow—COVseq—which can be used to generate highly multiplexed sequencing libraries compatible with Illumina platforms from hundreds of SARS-CoV-2 samples in parallel, in a rapid and cost-effective manner. We benchmark COVseq against a standard library preparation method (NEBNext) on 29 SARS-CoV-2 positive samples, reaching 95.4% of concordance between single-nucleotide variants detected by both methods. Application of COVseq to 245 additional SARS-CoV-2 positive samples demonstrates the ability of the method to reliably detect emergent VOC as well as its compatibility with downstream phylogenetic analyses. A cost analysis shows that COVseq could be used to sequence thousands of samples at less than 15 USD per sample, including library preparation and sequencing costs. We conclude that COVseq is a versatile and scalable method that is immediately applicable for SARS-CoV-2 genomic surveillance and easily adaptable to other pathogens such as influenza viruses.
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