Publications (9)24.62 Total impact
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Article: Oxidative stress due to radiation in CD34(+) hematopoietic progenitor cells: protection by IGF-1.
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ABSTRACT: Radiation exerts direct as well as indirect effects on DNA through the generation of reactive oxygen species (ROS). Irradiated hematopoietic progenitor cells (HPCs) experience DNA strand breaks, favoring genetic instability, due to ROS generation. Our aim was to study the effect of a range of radiation doses in HPCs and the possible protective mechanisms activated by insulin-like growth factor-1 (IGF-1). ROS generation was evaluated, in the presence or absence of IGF-1 in liquid cultures of human HPCs-CD34(+) irradiated with 1-, 2- and 5-Gy X-rays, using a flow cytometry assay. Manganese superoxide dismutase (MnSOD) expression was studied by western blot analysis and visualized by an immunofluorescence assay. Apoptosis was estimated using the following assays: Annexin-V assay, DNA degradation assay, BCL-2/BAX mRNA and protein levels and caspase-9 protein immunofluorescence visualization. Viability and clonogenic potential were studied in irradiated HPCs. The generation of superoxide anion radicals at an early and a late time point was increased, while the hydrogen peroxide generation at a late time point was stable. IGF-1 presence further enhanced the radiation-induced increase of MnSOD at 24 h post irradiation. IGF-1 inhibited the mitochondria-mediated pathway of apoptosis by regulating the m-RNA and protein expression of BAX, BCL-2 and the BCL-2/BAX ratio and by decreasing caspase-9 protein expression. IGF-1 presence in culture media of irradiated cells restored the clonogenic capacity and the viability of HPCs as well. In conclusion, IGF-1 protects HPCs-CD34(+) from radiation effects, by eliminating the oxidative microenvironment through the enhancement of MnSOD activation and by regulating the mitochondria-mediated pathway of apoptosis.Journal of Radiation Research 07/2012; 53(5):672-85. · 1.68 Impact Factor -
Article: Increased RANKL and IL-6 levels might result in high bone turnover in a case of a CD34+/CD117+/myeloperoxidase(+dim) acute myeloid leukemia presenting with severe hypercalcemia and lumbar spine fractures.
Leukemia research 07/2011; 35(11):e188-9. · 2.36 Impact Factor -
Article: Technetium-99m depreotide imaging by single photon emission tomography/low resolution computed tomography in malignant lymphomas: comparison with gallium-67 citrate.
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ABSTRACT: Previous studies have demonstrated the feasibility of targeting lymphoma lesions with somatostatin receptor binding agents, mainly with In-111-pentetreotide. In the present work another somatostatin analog, Tc-99m depreotide, is investigated. One-hundred and six patients, 47 with Hodgkin's (HL) and 59 with various types of non-Hodgkin's lymphoma (NHL), were imaged with both Tc-99m depreotide and Ga-67 citrate. Planar whole-body and single photon emission tomography/low resolution computerized tomography (SPECT/CT) images were obtained. A total of 142 examinations were undertaken at different phases of the disease. Depreotide and gallium findings were compared visually and semi-quantitatively, with reference to the results of conventional work-up and the patients' follow-up data. In most HL, intermediate- and low-grade B-cell, as well as in T-cell NHL, depreotide depicted more lesions than Ga-67 and/or exhibited higher tumor uptake. The opposite was true in aggressive B-cell NHL. However, there were notable exceptions in all lymphoma subtypes. During initial staging, 93.3% of affected lymph nodes above the diaphragm, 100% of inguinal nodes and all cases with splenic infiltration were detected by depreotide. On the basis of depreotide findings, 32% of patients with early-stage HL were upstaged. However, advanced HL and NHL cases were frequently downstaged, due to low sensitivity for abdominal lymph node (22.7%), liver (45.5%) and bone marrow involvement (36.4%). Post-therapy, depreotide detected 94.7% of cases with refractory disease or recurrence. Its overall specificity was moderate (57.1%). Rebound thymic hyperplasia, various inflammatory processes and sites of unspecific uptake were the commonest causes of false positive findings. The combination of depreotide and gallium enhanced sensitivity (100%), while various false positive results of either agent could be avoided. Except perhaps for early-stage HL, Tc-99m depreotide as a stand-alone imaging modality has limited value for the initial staging of lymphomas. Post-therapy, however, depreotide scintigraphy seems useful in the evaluation of certain anatomic areas, particularly in non-aggressive lymphoma types. The combination with Ga-67 potentially enhances sensitivity and specificity. If fluorodeoxyglucose positron emission tomography is not available or in case of certain indolent lymphoma types, Tc-99m depreotide may have a role as an adjunct to conventional imaging procedures.Annals of Nuclear Medicine 11/2010; 24(9):639-47. · 1.50 Impact Factor -
Article: Autophagy: novel action of panitumumab in colon cancer.
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ABSTRACT: Panitumumab, a fully-human monoclonal antibody raised against epidermal growth factor receptor (EGFR), has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of patients with EGFR-expressing metastatic colorectal carcinoma (mCRC) after failure of standard chemotherapy. Additionally, the guideline of the EMEA includes the use of panitumumab in patients with wild-type KRAS. The goal of the current study was to evaluate the effect of panitumumab on colon cancer cells, proliferation, apoptosis, necrosis, cell cycle arrest and autophagy. The effect of panitumumab on the redox status of the cells was also studied. The cell lines Caco-2, DLD-1 and HT-29 which differ in their expression of EGFR and HER-2 were used. Cell proliferation and apoptosis/necrosis were measured by methyl tetrazolium (MTT) assay and annexin V/propidium iodide assay, respectively. Cell cycle arrest was estimated by propidium iodide assay and autophagy was detected using Western blot analysis. Spectrophotometrical quantification of glutathione (GSH) levels and an analysis of KRAS sequence were applied. Panitumumab reduced proliferation only in the DLD-1 cells despite the mutated KRAS in this cell line. However, panitumumab did not affect DLD-1 cell apoptosis, necrosis or cell cycle progression. Interestingly, immunoblotting analysis revealed that panitumumab increased protein levels of beclin-1, a marker of autophagy. In addition, an increase in the GSH level was noted following panitumumab treatment reflecting an imbalance in the redox status of the cells. Panitumumab affects colon cancer cell proliferation independently of KRAS mutations and EGFR protein levels, possibly through the induction of autophagy.Anticancer research 12/2009; 29(12):5077-82. · 1.73 Impact Factor -
Article: Topical application of imiquimod induces alterations in peripheral blood lymphocytes in healthy individuals.
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ABSTRACT: The aim of this study was to determine whether imiquimod, a Toll-like receptor-7/8 agonist, in addition to its well-known topical action on the cutaneous immune response, might also induce alterations in the peripheral blood lymphocytes. A 62.5 mg quantity of imiquimod (5% cream) was applied topically under occlusion once daily every second day for 3 weeks to the skin of 10 healthy volunteers, age range 30-57 years. Ten sex- and age-matched healthy controls applied corresponding quantities of the vehicle under occlusion. Before, and one and 3 weeks after the start of treatment, peripheral blood lymphocyte subpopulations were measured by flow cytometry. Statistically significant alterations in the percentage or absolute numbers of peripheral blood lymphocyte subpopulations were found in the imiquimod-treated group compared with the control group. These alterations indicate for the first time that topical application of imiquimod induces alterations in peripheral blood lymphocyte subsets in healthy individuals, which may be of importance in the immunotherapy of neoplastic and infectious disorders and should be taken into careful consideration in patients who are treated with imiquimod.Acta Dermato Venereologica 02/2009; 89(2):134-9. · 3.18 Impact Factor -
Article: Abdominal radiation initiates apoptotic mechanism in rat femur bone marrow cells in vivo that is reversed by IGF-1 administration.
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ABSTRACT: Radiation induces apoptosis as a result of damage to cellular DNA and RNA. The aim of our work was to study the effect of radiation on rat bone marrow cells (as a neighboring tissue) in the context of a model of experimental radiation enteritis in rats. The effect of systematic administration in irradiated animals of r-IGF-1 and GH was also studied. Wistar type, normal rats, were divided in 4 groups. One control group and the other 3 groups were irradiated in the abdomen. The measured scattered irradiation in the femur ranged from 16.5 to 47.3 cGy. In 2 groups of irradiated animals, rIGF-1 (0.1 microg/g of body weight twice/d) and rGH (0.25 microg/g of body weight /d) were administered. Bone marrow cells were harvested from both femurs. DNA and RNA were analyzed in specific gels. The m-RNA was hybridized for c-fos proto-oncogene expression. The calculated low dose of radiation that affected the femurs of the animals induced reduction in bone marrow cell numbers and endonuclease activation manifested by subsequent fragmentation of DNA and RNA. This phenomenon was reversed by rGH and rIGF-1 administration. The c-fos proto-oncogene expression was upregulated by irradiation. These observations indicate that scattered low dose radiation is capable of initiating apoptosis in rat bone marrow cells and rGH and rIGF-1 administration reverse this process.Journal of Radiation Research 02/2008; 49(1):41-7. · 1.68 Impact Factor -
Article: Isolated granulocytic sarcoma involving the mediastinum and bilateral cervical lymph nodes.
European Journal Of Haematology 07/2007; 78(6):548. · 2.61 Impact Factor -
Article: Clinical relevance of balance between type 1 and type 2 immune responses of lymphocyte subpopulations in aplastic anaemia patients.
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ABSTRACT: Immune dysfunction, which leads to the suppression of haemopoiesis by cytokines that are secreted by activated T lymphocytes, is considered to play a key role in the pathogenesis of acquired aplastic anaemia (AAA). We investigated the intracytoplasmic expression of type-1 [interferon gamma (IFN-gamma), interleukin (IL)-2] and type-2 (IL-4, IL-10) cytokines in CD4+ and CD8+ T cells before and after in vitro activation in 16 patients with AAA and 17 normal controls. Untreated or refractory patients had a significantly higher proportion of unstimulated CD4+ and CD8+ T cells that produced IFN-gamma and IL-2 whereas the IL-4 and IL-10 producing T cells did not differ from that of controls, resulting in a shift of IFN-gamma/IL-4 ratio towards a type-1 response. Patients in remission had also increased proportion of IFN-gamma-producing unstimulated CD4+ and CD8+ cells, with a parallel rise of IL-4- and IL-10-producing cells and normal IFN-gamma/IL-4 ratio. These data indicate that, in newly diagnosed and refractory patients with AAA, CD4+ cells are polarized towards a type-1 response that in turn leads to activation of cytotoxic CD8+ cells and finally to haemopoietic stem cell destruction. The type-1 response persists in patients in remission although this effect is compensated by the increase of IL-4 and IL-10 production.British Journal of Haematology 02/2004; 124(1):97-105. · 4.94 Impact Factor -
Article: Clinical relevance of balance between type 1 and type 2 immune responses of lymphocyte subpopulations in aplastic anaemia patients
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ABSTRACT: Immune dysfunction, which leads to the suppression of haemopoiesis by cytokines that are secreted by activated T lymphocytes, is considered to play a key role in the pathogenesis of acquired aplastic anaemia (AAA).We investigated the intracytoplasmic expression of type-1 [interferon γ (IFN-γ), interleukin (IL)-2] and type-2 (IL-4, IL-10) cytokines in CD4+ and CD8+ T cells before and after in vitro activation in 16 patients with AAA and 17 normal controls. Untreated or refractory patients had a significantly higher proportion of unstimulated CD4+ and CD8+ T cells that produced IFN-γ and IL-2 whereas the IL-4 and IL-10 producing T cells did not differ from that of controls, resulting in a shift of IFN-γ/IL-4 ratio towards a type-1 response. Patients in remission had also increased proportion of IFN-γ-producing unstimulated CD4+ and CD8+ cells, with a parallel rise of IL-4- and IL-10-producing cells and normal IFN-γ/IL-4 ratio. These data indicate that, in newly diagnosed and refractory patients with AAA, CD4+ cells are polarized towards a type-1 response that in turn leads to activation of cytotoxic CD8+ cells and finally to haemopoietic stem cell destruction. The type-1 response persists in patients in remission although this effect is compensated by the increase of IL-4 and IL-10 production.British Journal of Haematology 12/2003; 124(1):97 - 105. · 4.94 Impact Factor
Top co-authors
Top Journals
Institutions
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2003–2012
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University of Patras
- • School of Medicine
- • Department of Nuclear Medicine
- • Department of Internal Medicine
Patrís, Kentriki Makedonia, Greece
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2011
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University General Hospital of Larissa
Lárisa, Thessalia, Greece
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2008
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Πανεπιστημιακό Γενικό Νοσοκομείο Πατρών
Pátrai, Ditiki Ellada, Greece
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