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- Erba, E, et al.
(författare)
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Effect of Aplidin in acute lymphoblastic leukaemia cells.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:4, s. 763-73
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Tidskriftsartikel (refereegranskat)abstract
- The cytotoxic effect of Aplidin was investigated on fresh leukaemia cells derived from children with B-cell-precursor (BCP) acute lymphoblastic leukaemia (ALL) by using stromal-layer culture system and on four cell lines, ALL-PO, Reh, ALL/MIK and TOM-1, derived from patients with ALL with different molecular genetic abnormalities. In ALL cell lines Aplidin was cytotoxic at nanomolar concentrations. In the ALL cell lines the drug-induced cell death was clearly related to the induction of apoptosis and appeared to be p53-independent. Only in ALL-PO 20 nM Aplidin treatment caused a block of vascular endothelial growth factor (VEGF) secretion and downregulation of VEGF-mRNA, but Aplidin cytotoxicity does not seem to be related to VEGF inhibition since the sensitivity of ALL-PO cells to Aplidin is comparable to that observed for the other cells used. Aplidin induced a G(1) and a G(2) M block in ALL cell lines. In patient-derived leukaemia cells, Aplidin induced a strong cytotoxicity evidenced in a stroma-supported immunocytometric assay. Cells from children with genetic abnormalities such as t(9;22) and t(4;11) translocations, associated with an inferior treatment outcome, were sensitive to Aplidin to the same extent as that observed in other BCP-ALL cases. Aplidin exerted a strong cell killing effect (>88%) against primary culture cells from five relapsed ALL cases, at concentrations much lower than those reported to be achieved in plasma of patients receiving Aplidin at recommended doses. Taken together these data suggest that Aplidin could be a new anticancer drug to be investigated in ALL patients resistant to available therapy.
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| 3. |
- Ardighieri, L, et al.
(författare)
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Infiltration by CXCL10 Secreting Macrophages Is Associated With Antitumor Immunity and Response to Therapy in Ovarian Cancer Subtypes
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 690201-
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian carcinomas (OCs) are poorly immunogenic and immune checkpoint inhibitors (ICIs) have offered a modest benefit. In this study, high CD3+ T-cells and CD163+ tumor-associated macrophages (TAMs) densities identify a subgroup of immune infiltrated high-grade serous carcinomas (HGSCs) with better outcomes and superior response to platinum-based therapies. On the contrary, in most clear cell carcinomas (CCCs) showing poor prognosis and refractory to platinum, a high TAM density is associated with low T cell frequency. Immune infiltrated HGSC are characterized by the 30-genes signature (OC-IS30) covering immune activation and IFNγ polarization and predicting good prognosis (n = 312, TCGA). Immune infiltrated HGSC contain CXCL10 producing M1-type TAM (IRF1+pSTAT1Y701+) in close proximity to T-cells. A fraction of these M1-type TAM also co-expresses TREM2. M1-polarized TAM were barely detectable in T-cell poor CCC, but identifiable across various immunogenic human cancers. Single cell RNA sequencing data confirm the existence of a tumor-infiltrating CXCL10+IRF1+STAT1+ M1-type TAM overexpressing antigen processing and presentation gene programs. Overall, this study highlights the clinical relevance of the CXCL10+IRF1+STAT1+ macrophage subset as biomarker for intratumoral T-cell activation and therefore offers a new tool to select patients more likely to respond to T-cell or macrophage-targeted immunotherapies.
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| 9. |
- Rothenberg, Elisabet, 1960-, et al.
(författare)
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SUN-P049: Nordic Healthy Diet and Mortality in a Cohort of 70 Year-Old Swedes : What is the Contribution of Dairy Intake?
- 2017
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Ingår i: Clinical Nutrition. - 0261-5614. ; 36, s. S71-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Rationale: Several definitions of the Nordic Healthy Diet havebeen proposed, but there is no consensus on the role of dairy products. We aim to study the impact of the Nordic diet on all- cause mortality in a population of 70 year-olds, exploring different versions of a Nordic Healthy Diet Score (NHDS) with focus on the specific role of key dairy products.Methods: Cox proportional hazard models, adjusted for potential confounders, were used to assess the prediction of all-cause mortality using two NHDS definitions (calculated either including low-fat or without dairy products). In separate Cox models, cheese intake and the combined intakes of milk, soured milk and unsweetened yoghurt were tested as well as intake of fat from these two sources.Results: Neither of the standard versions of NHDS was associated with mortality. However, cheese intake was pro- tective of total mortality, whereas milk products (including soured milk and unsweetened yoghurt) predicted increased risk of mortality. Cheese fat intake was also inversely associated with mortality, whereas fat from the other dairy products positively predicted the outcome only when the model was adjusted by energy intake.Conclusion: The NHDS, as previously defined, was not associated with all-cause mortality in this population of elderly[GT1] Swedes. Intake of milk, soured milk and/or unsweetened yoghurt was positively associated with all-cause mortality whereas cheese intake was inversely associated with this outcome.
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| 10. |
- Rothenberg, Elisabet, et al.
(författare)
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SUN-P049: Nordic Healthy Diet and Mortality in a Cohort of 70 Year-Old Swedes : What is the Contribution of Dairy Intake?
- 2017
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Ingår i: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 36
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Rationale: Several definitions of the Nordic Healthy Diet havebeen proposed, but there is no consensus on the role of dairy products. We aim to study the impact of the Nordic diet on all- cause mortality in a population of 70 year-olds, exploring different versions of a Nordic Healthy Diet Score (NHDS) with focus on the specific role of key dairy products. Methods: Cox proportional hazard models, adjusted for potential confounders, were used to assess the prediction of all-cause mortality using two NHDS definitions (calculated either including low-fat or without dairy products). In separate Cox models, cheese intake and the combined intakes of milk, soured milk and unsweetened yoghurt were tested as well as intake of fat from these two sources. Results: Neither of the standard versions of NHDS was associated with mortality. However, cheese intake was pro- tective of total mortality, whereas milk products (including soured milk and unsweetened yoghurt) predicted increased risk of mortality. Cheese fat intakewas also inversely associated with mortality, whereas fat from the other dairy products positively predicted the outcome only when the model was adjusted by energy intake. Conclusion: The NHDS, as previously defined, was not associated with all-cause mortality in this population of elderly[GT1] Swedes. Intake of milk, soured milk and/or unsweetened yoghurt was positively associated with all-cause mortality whereas cheese intake was inversely associated with this outcome.
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| 11. |
- Soldani, C, et al.
(författare)
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Poly(ADP-ribose) polymerase cleavage during apoptosis: when and where?
- 2001
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Ingår i: Experimental cell research. - : Elsevier BV. - 0014-4827. ; 269:2, s. 193-201
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Tidskriftsartikel (refereegranskat)abstract
- Poly(ADP-ribose) polymerase-1 (PARP-1) plays the active role of "nick sensor" during DNA repair and apoptosis, when it synthesizes ADP-ribose from NAD(+) in the presence of DNA strand breaks. Moreover, PARP-1 becomes a target of apoptotic caspases, which originate two proteolytic fragments of 89 and 24 kDa. The precise relationship between PARP-1 activation and degradation during apoptosis is still a matter of debate. In human Hep-2 cells driven to apoptosis by actinomycin D, we have monitored PARP-1 activity by the mAb 10H, which is specific for the ADP-ribose polymers, and we have observed that poly(ADP-ribose) synthesis is a very early response to the apoptotic stimulus. The analysis of the presence and fate of the p89 proteolytic fragment revealed that PARP-1 proteolysis by caspases is concomitant with poly(ADP-ribose) synthesis and that p89 migrates from the nucleus into the cytoplasm in late apoptotic cells with advanced nuclear fragmentation.
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| 12. |
- Tognon, M. S., et al.
(författare)
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Tuberculosis of the eye in Italy: a forgotten extrapulmonary localization
- 2014
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Ingår i: Infection. Zeitschrift für Klinik und Therapie der Infektionen. - : Springer Verlag (Germany). - 0300-8126 .- 1439-0973. ; 42:2, s. 335-342
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Tuberculosis (TB) of the eye is a well-known extrapulmonary localization in high-incidence countries. Data on its relevance in developed countries are scanty. We aim to study the epidemiological and clinical pattern of ocular TB in a tertiary care institution of a western country. Methods From 2007 to 2010, consecutive patients with a diagnosis of isolated ocular TB or associated to extraocular TB were recruited. Patients with ophthalmological and clinical features of TB were treated with standard antitubercular therapy (ATT) and steroids in case of concomitant severe ocular inflammation. Results Seventeen cases of ocular and extraocular TB and 45 cases of isolated ocular TB were identified. The proportion of patients with ocular and extraocular TB in our local district was 8.1 %, with a proportion of 10.6 % for the isolated cases. In Cohort 1, only one patient was symptomatic for ocular impairment, and uveitis without inflammation was the most common presentation. On the contrary, in Cohort 2, all patients had visual impairment, mainly with bilateral involvement. 77.8 % of the patients showed an inflammatory pattern. ATT was administered for at least 9 months, in four cases with a short course of systemic corticosteroids. Eight cases in Cohort 2 showed recurrence after 1 year from diagnosis. Conclusions TB of the eye should not be forgotten, even in geographical areas not considered among endemic countries. Ocular evaluation is advisable in patients with pulmonary and extrapulmonary TB, as early detection may allow ATT to preserve visual acuity.
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