| 1. |
- Ioannou, Nikolaos, et al.
(författare)
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Triggering interferon signaling in T cells with avadomide sensitizes CLL to anti-PD-L1 /PD-1 immunotherapy
- 2021
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 137:2, s. 216-231
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Tidskriftsartikel (refereegranskat)abstract
- Cancer treatment has been transformed by checkpoint blockade therapies, with the highest anti-tumor activity of anti-programmed death 1 (PD-1) antibody therapy seen in Hodgkin lymphoma. Disappointingly, response rates have been low in the non-Hodgkin lymphomas, with no activity seen in relapsed/refractory chronic lymphocytic leukemia (CLL) with PD-1 blockade. Thus, identifying more powerful combination therapy is required for these patients. Here, we preclinically demonstrate enhanced anti-CLL activity following combinational therapy with anti-PD-1 or anti-PD-1 ligand (PD-L1) and avadomide, a cereblon E3 ligase modulator (CELMoD). Avadomide induced type I and II interferon (IFN) signaling in patient T cells, triggering a feedforward cascade of reinvigorated T-cell responses. Immune modeling assays demonstrated that avadomide stimulated T-cell activation, chemokine expression, motility and lytic synapses with CLL cells, as well as IFN-inducible feedback inhibition through upregulation of PD-L1. Patient-derived xenograft tumors treated with avadomide were converted to CD8(+) T cell-inflamed tumor microenvironments that responded to anti-PD-L1/PD-1-based combination therapy. Notably, clinical analyses showed increased PD-L1 expression on T cells, as well as intratumoral expression of chemokine signaling genes in B-cell malignancy patients receiving avadomide-based therapy. These data of overcoming a low inflammatory T-cell state to successfully sensitize CLL to checkpoint illustrate the importance blockade-based combination therapy.
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| 2. |
- Papazoglou, D, et al.
(författare)
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Prevalence of hemochromatosis gene (HFE) mutations in Greece
- 2003
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Ingår i: Acta Haematologica. - : S. Karger AG. - 1421-9662 .- 0001-5792. ; 109:3, s. 137-140
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Tidskriftsartikel (refereegranskat)abstract
- The frequencies of the hereditary hemochromatosis gene (HFE) mutations C282Y and H63D vary between different populations. There are a limited number of reports regarding the frequency of these mutations in populations of southeastern Europe. Two hundred and sixty-four adult individuals of Greek origin were examined for the C282Y and H63D mutations to determine the allele and genotype frequencies. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by the polymerase chain reaction. Restriction enzyme analysis was performed using RsaI for C282Y and MboI for H63D. None of the 264 individuals carried the mutation C282Y. Forty-three individuals (16.2%) were heterozygous carriers of the H63D allele and 2 were homozygous for this mutation (0.75%). The overall H63D allele prevalence is thus estimated at 8.9%. HFE mutation frequencies were low in the population studied and this may explain, in part, the relative rarity of clinical cases of hereditary hemochromatosis in Greece. Copyright (C) 2003 S. Karger AG, Basel.
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| 3. |
- Papazoglou, D., et al.
(författare)
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The Fatty Acid Amide Hydrolase (FAAH) Pro129Thr Polymorphism is not Associated with Severe Obesity in Greek Subjects
- 2008
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Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 1439-4286 .- 0018-5043. ; 40:12, s. 907-910
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Tidskriftsartikel (refereegranskat)abstract
- Fatty amid acid hydrolase (FAAH) has been implicated at both protein and gene level with obesity. An association between Pro129Thr variant of the FAAH gene and obesity has been described, but various studies have yielded conflicting results. Our aim was to determine whether this polymorphism is related to severe obesity and whether it confers a risk for variability of quantitative metabolic traits in a cohort of Greek obese Subjects. Two groups of severely obese Subjects (BMI >40 kg/m(2)) were studied: a group of 158 metabolically healthy and a group of 145 obese subjects with metabolic syndrome, which were compared to a Control group consisting of 121 lean individuals. We did not find any association between the Pro129Thr polymorphism with severe obesity in both subgroups of obese subjects, between these two subgroups (p = 0.11) or on basic anthropometric characteristics in the three groups. Statistically significant differences were found for glucose and HDL in metabolically healthy Subjects and HDL in the control group. The borderline significant p-values were not significant after correction for multiple testing. We were unable to find robust evidence of an association of the Pro 129Thr variant with severe obesity, and any related quantitative traits among the obese Greek Subjects examined.
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| 4. |
- Papazoglou, D, et al.
(författare)
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Vascular endothelial growth factor gene polymorphisms and pre-eclampsia
- 2004
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Ingår i: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407. ; 10:5, s. 321-324
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF) plays a crucial role in physiological vasculogenesis and vascular permeability and has been implicated in the pathogenesis of pre-eclampsia. Our present study was undertaken to identify associations between three functional VEGF gene polymorphisms, linked with altered VEGF gene responsiveness, and pre-eclampsia. The study involved 42 pre-eclamptic and 73 healthy control women who were genotyped for the -2578C/A, -634G/C and 936C/T polymorphisms of the VEGF gene. No significant association between genotypic or allelic frequencies in women with pre-eclampsia relative to controls was found. A statistically significant difference was found for allelic frequencies of the 936C/T polymorphism between women with severe pre-eclampsia and controls (odds ratio: 2.70; 95% confidence interval: 1.09-6.63; P = 0.019). VEGF gene polymorphisms studied are unlikely to be major predisposing factors for pre-eclampsia. The presence of the 936T allele probably has a considerable effect on disease modification.
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