Biomedical subjects

Panagiotis Kanavaros

Publications and source records attributed to Panagiotis Kanavaros.

13 recordsLinked to original sources

PubMed2006

Expression of bcl2 family proteins and active caspase 3 in classical Hodgkin's lymphomas.

The expression of various bcl2 family proteins has been reported in Hodgkin and Reed-Sternberg cells, but the proteins bad, bid, and bim have not been analyzed in classical Hodgkin's lymphomas (HLs). This study aimed to investigate the expression of the proteins bcl2, bcl-xl, mcl1, bax, bak, bad, bid, bim, and active caspase 3, and the TUNEL (terminal deoxynucleotidyl transferase-mediated in situ labeling) index to gain further insight into the apoptosis profile of classical HLs. A high expression of the proteins bcl2, bcl-xl, mcl1, bax, bak, bad, bid, and bim in HRS cells was found in 27 of 101 (27%), 95 of 101 (94%), 27 of 97 (29%), 73 of 95 (77%), 37 of 102 (36%), 85 of 94 (90%), 19 of 109 (17%), and 43 of 91 (47%) cases, respectively. The high expression of bcl-xl, bax, and bad in HRS cells in most classical HLs indicates that these proteins may play predominant roles in the regulation of apoptosis in classical HLs. Active caspase 3-positive and TUNEL-positive Reed-Sternberg cells were detected in 47 of 70 (67%; range, 0%-12%) and 60 of 71 (85%; range, 0%-19%) cases, respectively. Significant positive correlations were found between bax/bcl2 (P = .002), bad/bcl2 (P = .020), bad/bcl-xl (P = .003), and bim/mcl1 (P = .036). Based on these findings, it could be hypothesized that the antiapoptotic proteins bcl2, bcl-xl, and mcl1 may counteract the expression of the proapoptotic proteins bax, bad, and bim, thereby contributing to the survival of Reed-Sternberg cells.

Apoptosis↗

PubMed2006

B-cell differentiation immunophenotypes in classical Hodgkin lymphomas.

The bcl6/CD10/MUM1/CD138 B-cell differentiation immunophenotypes were analysed in 101 cases of classical Hodgkin lymphomas (cHL) aiming to elucidate their histogenesis. Three major bcl6/CD10/MUM1/CD138 immunophenotypes were distinguished on the basis of the immunohistochemical positivity of Hodgkin and Reed-Sternberg (H/RS) cells: (a) the late germinal center (GC)/early post-GC B-cell-like immunophenotype (bcl6-/CD10-/MUM1+/CD138-); 59/101 cases (59%), (b) the post-GC B-cell-like immunophenotype (bcl6-/CD10-/MUM1+/CD138+); 24/101 cases (24%) and (c) the indeterminate immunophenotype (bcl6+/CD10-/MUM1+/CD138-: 14 cases and bcl6+/CD10-/MUM1+/CD138+: four cases); 18/101 cases (18%). The above findings indicate that H/RS cells in most cHL display bcl6/CD10/MUM1/CD138 immunophenotypes consistent with late GC/early post-GC or post-GC B-cell differentiation. In addition, H/RS cells in a small fraction of cHL display indeterminate bcl6/CD10/MUM1/CD138 immunophenotypic profiles which are characterized by simultaneous expression of GC, late GC/early post-GC and post-GC B-cell differentiation proteins. These immunophenotypic profiles do not correspond to the differentiation immunophenotypes of normal B-cells and their identification in a part of cHL suggests that the differentiation process of H/RS cells is not complete in a fraction of these cells and/or is still ongoing at the time of observation.

Antigens, Differentiation↗

PubMed2005

Mitochondria-rich normal, metaplastic, and neoplastic cells show overexpression of the epitope H recognized by the monoclonal antibody H.

The epitope H contains an O-linked N-acetylglucosamine (O-GlcNAc) residue in a specific conformation and/or environment recognized by monoclonal antibody H (mAbH). We have previously shown that the epitope H is present in more than one polypeptide and in various types of normal and pathological cells. In the present study, we focused on mitochondria-rich normal, metaplastic, and neoplastic cells, prompted by our recent immuno-electron microscopy findings that mAbH clearly stains the mitochondria of breast epithelial cells in infiltrating ductal breast carcinomas and fibroadenomas. The indirect immunoperoxidase method was applied using the mAbH to investigate the distribution of the epitope H in mitochondria-rich normal cells and in metaplastic and neoplastic oncocytic cells. Immunohistochemical staining for the mAbH was observed in oxyphil cells of parathyroid glands, in striated duct cells of parotid glands, in urinary tubules of kidneys, in parietal cells of gastric body mucosa, in oxyphil cells of Hashimoto's thyroiditis, in epithelial cells of Warthin's tumors of the parotid gland, in neoplastic cells of oxyphil adenomas and carcinomas (Hürthle's tumors) of the thyroid gland, and in neoplastic cells of oncocytomas of the kidneys. The present study shows that the epitope H is strongly expressed in mitochondria-rich normal cells, as well as in metaplastic and neoplastic oncocytic cells, which are known to have cytoplasms packed with mitochondria. Since mAbH recognizes an O-GlcNAc residue, our findings indicate that O-GlcNAc-glycosylated polypeptides are present at mitochondria where the components of the respiratory chain and energy transduction are localized. These findings may be of interest for gaining insight into the histophysiology of mitochondria-rich normal cells and into the pathogenesis of oncocytic lesions, since O-GlcNAc glycosylation may modify proteins involved in oncogenesis such as tumor suppressor proteins and oncoproteins, as well as proteins with important biological functions such as cytoskeletal proteins, transcription factors, heat-shock proteins, and chromatin proteins.

Acetylglucosamine↗

PubMed2005

Effects of adrenergic agents on rat peritoneal macrophages activated in vitro by acetylated low-density lipoprotein.

Macrophages interact with modified lipoproteins and alter their functional status. In this study, the effects of the adrenergic agents adrenaline, isoproterenol, and dobutamine on macrophages activated with acetylated low-density lipoprotein were tested. The aim of this investigation was to determine whether adrenergic agents influence biologically significant functions of these cells in an in vitro model of macrophage-lipoprotein acute interaction. Rat peritoneal macrophages were incubated with acetylated low-density lipoprotein for 16 h, with or without adrenergic agents. Hydrogen peroxide and nitric oxide production and acid phosphatase activities in the supernatant and cell lysate were assayed. Adrenaline and isoproterenol inhibited the production of hydrogen peroxide, stimulated the production of nitric oxide, and increased the extracellular activity of acid phosphatase in the lipoprotein-activated cells. Dobutamine increased the extracellular, but decreased the intracellular acid phosphatase activity. Adrenaline and dobutamine also produced changes in the cell size and nuclear morphology of the macrophages. Macrophages are activated in vitro by acetylated low-density lipoprotein, and their functions and morphology are modified under the influence of adrenergic agents. Certain effects could be attributed to changes in cyclic AMP levels.

Acid Phosphatase↗

PubMed2004

Diffuse large B-cell lymphomas with germinal center B-cell-like differentiation immunophenotypic profile are associated with high apoptotic index, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl.

The aim of this study was to analyze the relations between differentiation immunophenotypes and the status of apoptosis and proliferation in diffuse large B-cell lymphomas. Therefore, the bcl6/CD10/MUM1/CD138 differentiation immunophenotypic profiles were studied in relation to (a) the apoptotic index, (b) the apoptosis-associated bcl2 family proteins bcl2, bcl-xl, bax, bak, bad and bid, (c) the proliferation index (Ki67) and (d) the cell cycle proteins cyclin A, cyclin B1, cyclin D3, cyclin E, p53, Rb, p16 and p27 in 79 cases of diffuse large B-cell lymphomas. Two major differentiation immunophenotypic profiles were distinguished: the germinal center B-cell-like profile; 31 cases (bcl6+/CD10+/-/MUM1-/CD138-: 29 cases and bcl6-/CD10+/MUM1-/CD138-: two cases) and the nongerminal center B-cell-like profile (bcl6+/-/CD10-/MUM1+/CD138-); 48 cases. The expression of bax, bak and bid and the apoptotic index were significantly higher in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.045, 0.018, 0.003 and 0.034, respectively). In contrast, the expression of bcl-xl was significantly lower in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.026). The expression of bcl6 and CD10 showed significant positive correlation with the expression of bax (r=0.659, P<0.001 and r=0.240, P=0.033, respectively), bak (r=0.391, P<0.001 and r=0.233, P=0.039, respectively) and bid (r=0.652, P<0.001 and r=0.238, P=0.035, respectively) and significant negative correlation with the expression of bcl-xl (r=-0.536, P<0.001 and r=-0.250, P=0.029, respectively). The expression of MUM1 showed significant negative correlation with the expression of bax (r=-0.276, P=0.014) and bid (r=-0.266, P=0.018) and significant positive correlation with the expression of bcl-xl (r=0.238, P=0.037). The above findings indicate that diffuse large B-cell lymphomas with germinal center B-cell-like immunophenotypic profile are associated with increased apoptosis status, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl.

Apoptosis↗

PubMed2004

Proliferation profile of classical Hodgkin's lymphomas. Increased expression of the protein cyclin D2 in Hodgkin's and Reed-Sternberg cells.

There is accumulating evidence that Hodgkin's and Reed-Sternberg cells of classical Hodgkin's lymphomas (cHL) display multiple and concurrent alterations in different pathways and checkpoints of the cell cycle. However, the expression of cyclin D2 and its relation to other major cell cycle proteins has not been analyzed in cHL. The aim of the present study was to assess expression of cyclin D2, Ki67, cyclin A, cyclin B1, cyclin D1, cyclin D3, cyclin E, p53, Rb, p16 and p27 proteins in order to gain further insight into the proliferation profile of cHL. Overexpression of cyclin D2 in Hodgkin's and Reed-Sternberg cells was detected in 64/89 (72%) cases of cHL. This finding, in view of recent in vitro data showing that constitutive activation of nuclear factor (NF)-kB could upregulate cyclin D2 expression in part via signal transducer and activator of transcription (STAT)-5a, suggests that induction of cyclin D2 expression may support the proliferation of Hodgkin's and Reed-Sternberg cells. In addition, the present study showed that (1) increased p27 expression status was significantly correlated with higher levels of cyclin A expression (P=0.048) and (2) increased p53 expression status was significantly correlated with higher levels of cyclin A (P<0.001) and cyclin B1 (P=0.040) expression. The association between increased p27 and p53 expression status and higher expression levels of G2/M cyclins suggests that the impairment of the growth inhibitory activity of the p27 and p53 tumor suppressor pathways may promote the proliferation of Hodgkin's and Reed-Sternberg cells.

Cell Cycle↗

PubMed2004

Blastic natural killer (NK)-cell lymphoma: report of an unusual CD4 negative case and review of the CD4 negative neoplasms with blastic features in the literature.

Blastic Natural Killer (NK)-cell lymphoma is a relatively new entity which has been recently included in the WHO classification. CD4 expression is observed in most cases of blastic NK-cell lymphomas and has been related with skin tropism. We report an unusual CD4 negative blastic NK-cell lymphoma with primary presentation in the skin, subsequent infiltration of the bone marrow and aggressive behavior. It is emphasized that extensive immunophenotyping and EBER RNA in situ hybridization are required in order to establish the diagnosis of blastic NK-cell lymphoma. We also present a review of the literature with respect to the CD4 negative NK-cell lymphomas with blastic morphological features.

Adult↗

PubMed2003

Angiographic findings and clinical implications of persistent primitive hypoglossal artery.

BACKGROUND: The primitive hypoglossal artery (PHA) is a rare vascular anomaly, which belongs to the group of carotid-basilar anastomosis that may occur in adults. CASE PRESENTATION: Herein is presented a case of a patient with a PHA, who had undergone a cerebral angiography due to investigation of subarachnoid hemorrhage. Additionally, the diagnostic alternatives for detection and assessment of PHA and the spectrum of diseases related to its presence are discussed. CONCLUSIONS: The presence of a persistent PHA can be recognized as an incidental finding in a cerebral angiography without any other clinical implication or may be associated with certain clinical entities such as aneurysm formation and atherosclerotic disease.

Journal Article↗

PubMed2003

Fraction of the peripheral blood concentration of CD56+/CD16-/CD3- cells in total natural killer cells as an indication of fertility and infertility.

OBJECTIVE: To determine whether the peripheral blood concentration of CD56(+)/CD16(-)/CD3(-) cells, the main natural killer (NK) subpopulation that colonizes the endometrium in the middle and late secretory phase, can be related to fertility or infertility status. DESIGN: A case control study. SETTING: Immunopathology department of an infertility laboratory. PATIENTS: A total 99 women were selected (group I: consecutive spontaneous aborters, n = 25; group II: sporadic spontaneous aborters, n = 30; group III: infertile, n = 33; group IV: controls, n = 11). INTERVENTION: Immunophenotyping of women grouped according to their fertility status. MAIN OUTCOME MEASURES: Peripheral blood lymphocytes were examined by two- and three-color flow cytometry. RESULTS: A statistically significant association between endometrial-type peripheral blood (PB) NK cell concentrations and fertility status (groups I and IV vs. groups II and III) was documented. The %(/TOTAL PB)(CD56+CD16-CD3-) NK cells was significantly higher [1] in fertile (groups I and IV) than in sporadic aborters/infertile (groups II and III) women, [2] in group I when compared with groups II and III, and [3] in group IV when compared with groups II and III. CONCLUSIONS: This study indicates that diminished numbers of the %(/TOTAL PB)(CD56+CD16-CD3-) NK cells are related to sporadic aborters and infertile women. Thus, the fraction could be used as an indicator of subsequent successful implantation and maintenance of gestation.

Abortion, Habitual↗

PubMedDate not supplied

Cluster analysis of apoptosis-associated bcl2 family proteins in diffuse large B-cell lymphomas. Relations with the apoptotic index, the proliferation profile and the B-cell differentiation immunophenotypes.

BACKGROUND: There is evidence that apoptotic mechanisms mediated by bcl2 family proteins are involved in the pathogenesis of diffuse large B-cell lymphomas (DLBCL). In order to gain further insight into the apoptosis profile of DLBCL, 79 cases were investigated to determine whether distinct clusters of the combined expression levels of bcl2 family proteins can be identified in these lymphomas. MATERIALS AND METHODS: The combined immunohistochemical expression levels of the proteins bax, bak, bad, bid, bcl2 and bcl-xl were evaluated by cluster and discriminant analysis. The produced clusters were analyzed in relation to the apoptotic index, the proliferation profile and the B-cell differentiation immunophenotypes. RESULTS: Cluster analysis produced: a) a low expression (69/79 cases) and a high expression pro-apoptotic cluster (10/79 cases) for the combined expression levels of the pro-apoptotic proteins bax, bak, bad and bid and b) a low expression (37/76 cases) and a high expression antiapoptotic cluster (39/76 cases) for the combined expression levels of anti-apoptotic proteins bcl2 and bcl-xl. The decreasing order of discriminant power for the percentages of tumor cells expressing pro-apoptotic and anti-apoptotic proteins was % bax + cells> % bak+ cells> % bid+ cells> % bad+ cells and % bcl2+ cells> % bcl-xl+ cells, respectively. The high expression pro-apoptotic cluster was significantly associated with higher mean values of Ki67 (p=0.047) and cyclin A (p=0.033) expression. The high expression pro-apoptotic cluster was significantly associated with the germinal center B-cell bc16/CD10/MUM1/CD138 differentiation immunophenotype (p=0.043). CONCLUSION: This study identified distinct clusters of DLBCL with respect to the combined expression levels of the apoptosis-associated bcl2 family proteins. These findings, taken together with our previous observations that distinct clusters with respect to the apoptotic index and the proliferation profile are identified in DLBCL, indicate that subgroups with distinct cellular kinetic properties can be defined in these lymphomas. The cluster analysis approach might be useful for the identification of subgroups of DLBCL with different clinical behavior since increased proliferation and apoptosis were reported to be associated with aggressive tumor behavior in these lymphomas.

Apoptosis↗

PubMedDate not supplied

The effects of phosphoinositide/calcium- or cyclic AMP-mediated signal transduction pathway inhibitors on the activation of rat peritoneal macrophages by acetylated low-density lipoprotein.

BACKGROUND: Macrophages that uptake modified lipoproteins are activated and may initially behave as endotoxin-stimulated macrophages. This study was undertaken in order to determine whether signal transduction pathways controlling endotoxin-mediated activation may also influence the lipoprotein-mediated activation of macrophages. MATERIALS AND METHODS: Rat peritoneal macrophages were incubated for 16 hours with acetylated low-density lipoprotein and certain agents that modify the phosphoinositide/calcium- and cyclic AMP-mediated pathways, such as 2-[4-morpholinyl]-8-phenyl-1[4H]-benzopyran-4-one (LY-294002), autocamtide 2-related inhibitory peptide (AIP), N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide hydrochloride (H-89) and actinomycin D. The production of nitric oxide and the intracellular and extracellular activities of acid phosphatase were assayed. RESULTS: Macrophages incubated with acetylated low-density lipoprotein showed an increased production of nitric oxide and intracellular acid phosphatase activity as compared to their controls. LY-294002, AIP and H-89 caused a significant decrease in nitric oxide production and intracellular acid phosphatase activity. Actinomycin D had similar effects. AIP and actinomycin also significantly increased extracellular acid phosphatase activity. CONCLUSION: The activation of peritoneal macrophages by acetylated low-density lipoprotein was similar to the activation by endotoxin, as expressed by the nitric oxide production and acid phosphatase intracellular activity; agents controlling the phosphoinositide/calcium- and cyclic AMP-mediated pathways in endotoxin-activated macrophages also influence the acetylated low-density lipoprotein-activated macrophages.

Acid Phosphatase↗

PubMedDate not supplied

Cell cycle and apoptosis deregulation in classical Hodgkin lymphomas.

Classical Hodgkin lymphomas (cHL) have now been recognized as B-cell lymphomas with some exceptional cases of T-cell origin. In recent years, there has been accumulating evidence that Hodgkin and Reed-Sternberg (H/RS) cells, the presumed neoplastic-cell population in cHL, are characterized by a profound disturbance of the cell cycle and apoptosis regulation. The constitutive activation of the nuclear factor (NF)-kappaB pathway, which is considered to be involved in the proliferation and survival of H/RS cells. Moreover, substantial evidence that H/RS cells have defective cell cycle and apoptosis regulation has been provided by studies showing that these cells are characterized, in a large proportion of cases, by alterations of the p53, Rb and p27 tumor suppressor pathways, overexpression of cyclins involved in the G1/S and G2/M transition such as cyclins E, D2, D3, A and B1, overexpression of cyclin-dependent kinases such as CDK1, 2 and 6 and overexpression of anti-apoptotic proteins such as c-FLIP, bcl-xl, c-IAP2, X-linked I4P and survivin. Recent studies suggest that interleukin 13 (IL-13) is an important growth and survival factor in H/RS cells. Furthermore, the Epstein-Barr Virus (EBV), which is present in H/RS cells in about 30-50% of cHL, has been shown to affect the cell cycle and apoptosis regulation in cHL. The present review summarizes data with respect to the cell cycle and apoptosis deregulation in cHL.

Apoptosis↗

PubMedDate not supplied

B-cell differentiation, apoptosis and proliferation in diffuse large B-cell lymphomas.

Diffuse large B-cell lymphomas (DLBCL) represent the most common type of adult non-Hodgkin's lymphomas in Western countries and are characterized by heterogeneous clinical, histological, immunophenotypic and genetic features. Recent investigations using cDNA and oligonucleotide microarrays have identified molecularly distinct groups of DLBCL with respect to the B-cell differentiation gene expression profile: the germinal center (GC) B-cell-like DLBCL, the activated B-cell-like DLBCL and the type 3 DLBCL. The GC B-cell-like DLBCL were characterized by the expression of genes of the normal GC B-cells, the activated B-cell-like DLBCL were characterized by the expression of genes that are normally induced luring in vitro activation of peripheral blood B-cells, while the type 3 DLBCL did not express either set of genes at a high level. Patients with GC B-cell-like DLBCL had more favorable clinical outcome than those with activated B-cell-like or type 3 DLBCL. Immunohistochemical studies have shown that the bc16/CD10/MUM1/CD138 B-cell differentiation immunophenotypes are prognostically relevant and may predict the cDNA classification in a sizable fraction of DLBCL. In the last few years, there has been accumulating molecular and immunohistochemical evidence indicating links between B-cell differentiation gene expression profiles and expression of apoptosis and cell cycle-associated genes in DLBCL. The present review summarizes data with respect to the relationships between B-cell differentiation, apoptosis and proliferation in DLBCL.

Animals↗