Alexandra Giatromanolaki

Democritus University of Thrace, Komotina, East Macedonia and Thrace, Greece

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Publications (326)1165.61 Total impact

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    ABSTRACT: ABSTRACT Glioblastoma cells are resistant to apoptotic stimuli with autophagic death prevailing under cytotoxic stress. Autophagy interfering agents may represent a new strategy to test in combination with chemo-radiation. We investigated the patterns of expression of autophagy related proteins (LC3A, LC3B, p62, Beclin 1, ULK1 and ULK2) in a series of patients treated with post-operative radiotherapy. Experiments with glioblastoma cell lines (T98 and U87) were also performed to assess autophagic response under conditions simulating the adverse intratumoral environment. Glioblastomas showed cytoplasmic overexpression of autophagic proteins in a varying extent, so that cases could be grouped into low and high expression groups. 10/23, 5/23, 13/23, 5/23, 8/23 and 9/23 cases examined showed extensive expression of LC3A, LC3B, Beclin 1, Ulk 1, Ulk 2 and p62, respectively. Lysosomal markers Cathepsin D and LAMP2a, as well as the lyososomal biogenesis transcription factor TFEB were frequently overexpressed in glioblastomas (10/23, 11/23, and 10/23 cases, respectively). TFEB was directly linked with PTEN, Cathepsin D, HIF1α, LC3B, Beclin 1 and p62 expression. PTEN was also significantly related with LC3B but not LC3A expression, in both immunohistochemistry and gene expression analysis. Confocal microscopy in T98 and U87 cell lines showed distinct identity of LC3A and LC3B autophagosomes. The previously reported stone-like structure (SLS) pattern of LC3 expression was related with prognosis. SLS were inducible in glioblastoma cell lines under exposure to acidic conditions and 2DG mediated glucose antagonism. The present study provides the basis for autophagic characterization of human glioblastoma for further translational studies and targeted therapy trials.
    Cancer biology & therapy 08/2014; · 3.29 Impact Factor
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    ABSTRACT: Vasculature damage is an important contributor to the side-effects of radiotherapy. The aim of this study is to provide insights into the radiobiology of the autophagic response of endothelial cells.
    PLoS ONE 07/2014; 9(7):e102408. · 3.53 Impact Factor
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    ABSTRACT: Background: Radiotherapy for lung cancer may induce pneumonitis. However, histological effects of radiotherapy on normal lung tissue are unknown. Transbronchial biopsy (TBB) is safe and accurate in monitoring parenchymal lesions in lung-transplanted patients. The aim of this prospective study was to evaluate whether histological changes of the healthy lung parenchyma after radiotherapy are present on TBB biopsies. Patients and Methods: Twelve patients with lung cancer necessitating radiation therapy participated in the study. Serial TBBs were obtained from lung parenchyma contra-lateral to the tumor before, just after radiotherapy, and at six months post-irradiation. Evaluation of each specimen was based on the presence of congestion, inflammation, hemorrhage and fibrosis. Results: A significant increase of interstitial fibrosis (thickness) and congestion was observed between the point prior to radiotherapy and after completion of radiotherapy (p=0.047), as well as between the pre-radiotherapy point and at six months after radiotherapy (p=0.014). Six patients (50%) showed intra-alveolar fibroblastic growth after radiotherapy. No patient showed clinical or radiographic findings of radiation pneumonitis. Conclusion: Even in the absence of clinical or radiographic findings, the lung parenchyma contra-lateral to the tumor suffers early histological lesions after radiation therapy, as monitored by serial TBBs.
    Anticancer research 06/2014; 34(6):3119-3124. · 1.87 Impact Factor
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    ABSTRACT: Idiopathic eosinophilic pleural effusions (IEPE) comprise the eosinophilic pleural effusions for which a specific aetiology cannot be established. There are no reports investigating IEPE on the basis of a systematically applied pleuroscopy approach and entailing an appropriate patient follow-up till the final outcome is established; existing series rather combine clinical and thoracocentesis criteria to establish the idiopathic character of the diagnosis.
    The Clinical Respiratory Journal 05/2014; · 1.66 Impact Factor
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    ABSTRACT: Delta-like ligand 4 (DLL4) is a ligand of the notch pathway. In tumor angiogenesis, DLL4 switches to vascular maturation by providing a negative feedback on VEGFR2 activity. We investigated the expression of DLL4 in the plasma and cancer tissues from breast cancer patients. Plasma samples were collected from 18 women with localized breast cancer, six women with benign breast disease and from six patients with widespread metastatic disease. DLL4 was assessed using ELISA and in cancer tissues using immunohistochemistry. Patients with metastatic breast cancer had significantly higher levels (median 6.7 ± 0.81 ng/ml) compared to patients with localized tumors (median 5.4 ± 0.70 ng/ml) (p = 0.005) and to patients with benign breast disease (median 4.3 ± 0.28) (p = 0.0003). High histology grade was significantly linked with higher plasma DLL4 levels (median 5.59 ± 0.62 vs. 5.12 ± 0.44 ng/ml; p = 0.01). Surgical removal of high-grade breast cancer resulted in significant reduction in DLL4 plasma levels (p = 0.003). DLL4 was expressed in tumor-associated vessels and in cancer cells. The ratio of DLL4+/CD31+ vascular density (VD) ranged from 23 to 88 % (median 49 %). High DLL4 cancer cell expression and high DLL4+ VD were significantly linked with nodal involvement (p = 0.004 and 0.01, respectively). Linear regression analysis showed a significant association of DLL4 plasma levels with the percentage of DLL4+ cancer cells (p = 0.03, r = 0.50) and with DLL4+ VD (p = 0.0007, r = 0.60). It is concluded that DLL4 is overexpressed in breast cancer cells and breast cancer vasculature and is linked with nodal and distant metastasis. DLL4 plasma levels measurement can reliably estimate the total DLL4 breast cancer/vasculature activity.
    Medical Oncology 05/2014; 31(5):945. · 2.06 Impact Factor
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    ABSTRACT: Background:Although Trastuzumab has improved survival of HER2+ breast cancer patients, resistance to the agent pre-exists or develops through the course of therapy. Here we show that a specific metabolism and autophagy-related cancer cell phenotype relates to resistance of HER2+ breast cancer to Trastuzumab and chemotherapy.Methods:Twenty-eight patients with locally advanced primary breast cancer were prospectively scheduled to received one cycle of Trastuzumab followed by a new biopsy on day 21, followed by taxol/Trastuzumab chemotherapy for four cycles before surgery. FDG PET/CT scan was used to monitor tumour response. Tissue samples were immunohistochemically analysed for metabolism and autophagy markers.Results:In pre-Trastuzumab biopsies, the LC3A+/HER2+ cell population was correlated with HIF1α expression (P=0.01), while GLUT1 and LC3B expression were correlated with Ki67 proliferation index (P=0.01 and P=0.01, respectively). FDG PET tumour dimensions before therapy were correlated with LC3B expression (P=0.005). Administration of Trastuzumab significantly reduced clinical and PET-detected tumour dimensions (P<0.01). An inverse association of tumour response with the percentage of cells expressing HIF1α at baseline was documented (P=0.01). Administration of Trastuzumab resulted in a decrease of the proliferation index (P=0.004), GLUT1 (P=0.04) and HER2 (P=0.01) expression. In contrast, the percentage of LC3A+/HER2+ cells was increased (P=0.01). High baseline HIF1α expression was the only parameter associated with poorer pathological response to preoperative chemotherapy (P=0.001).Conclusions:As the HER2+/LC3A+ phenotype, which often overexpresses HIF1α, is a major subpopulation increasing after therapy with Trastuzumab, LC3A- and HIF1α-targeting therapies should be investigated for the augmentation of anti-HER2 therapy efficacy.British Journal of Cancer advance online publication, 10 April 2014; doi:10.1038/bjc.2014.196
    British Journal of Cancer 04/2014; · 5.08 Impact Factor
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    ABSTRACT: Background:Radiotherapy provides high-cure rates in prostate cancer. Despite its overall slow clinical growth, high proliferation rates documented in a subset of tumours relate to poor radiotherapy outcome. This study examines the role of anaerobic metabolism in prostate cancer growth and resistance to radiotherapy.Methods:Biopsy samples from 83 patients with prostate cancer undergoing radical hypofractionated and accelerated radiotherapy were analysed for MIB1 proliferation index and for lactate dehydrogenase isoenzyme LDH5, a marker of tumour anaerobic metabolism. Ninety-five surgical samples were in parallel analysed. Correlation with histopathological variables, PSA and radiotherapy outcome was assessed. Dose-response experiments were performed in PC3 and DU145 cancer cell lines.Results:High MIB1 index (noted in 25% of cases) was directly related to Gleason score (P<0.0001), T3-stage (P=0.0008) and PSA levels (P=0.03). High LDH5 (noted in 65% of cases) was directly related to MIB1 index (P<0.0001), Gleason score (P=0.02) and T3-stage (P=0.001). High Gleason score, MIB1, LDH5 and PSA levels were significantly related to poor BRFS (P=0.007, 0.01, 0.03 and 0.01, respectively). High Gleason score (P=0.04), LDH5 (P=0.01) and PSA levels (P=0.003) were significantly related to local recurrence. MIB1 and T-stage did not affect local control. Silencing of LDHA gene in both prostate cancer cell lines resulted in significant radiosensitisation.Conclusions:LDH5 overexpression is significantly linked to highly proliferating prostate carcinomas and with biochemical failure and local relapse following radiotherapy. Hypoxia and LDHA targeting agents may prove useful to overcome radioresistance in a subgroup of prostate carcinomas with anaerobic metabolic predilection.British Journal of Cancer advance online publication, 8 April 2014; doi:10.1038/bjc.2014.158
    British Journal of Cancer 04/2014; · 5.08 Impact Factor
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    ABSTRACT: Neutrophil activation by inflammatory stimuli and the release of extracellular chromatin structures, (neutrophil extracellular traps - NETs), have been implicated in inflammatory disorders. Herein, we demonstrate that NETs released by neutrophils treated either with fibrosis-related agents, such as cigarette smoke, magnesium silicate, bleomycin or generic NET inducers, such as phorbol 12-myristate 13-acetate, induced activation of lung fibroblasts (LFs) and differentiation into myofibroblast (MF) phenotype. Interestingly, the aforementioned agents or IL-17 (a primary initiator of inflammation/fibrosis) had no direct effect on LF activation and differentiation. MFs treated with NETs demonstrated increased connective tissue growth factor expression, collagen production and proliferation/migration. These fibrotic effects were significantly decreased after degradation of NETs with DNase1, heparin or myeloperoxidase inhibitor, indicating the key role of NET-derived components in LF differentiation and function. Furthermore, IL-17 was expressed in NETs and promoted the fibrotic activity of differentiated LFs but not their differentiation, suggesting that priming by DNA and histones is essential for IL-17-driven fibrosis. Additionally, autophagy was identified as orchestrator of NET formation, as shown by inhibition studies using bafilomycin A1 or wortmannin. The above findings were further supported by the detection of NETs in close proximity to alpha-smooth muscle actin (α-SMA) expressing fibroblasts in biopsies from patients with fibrotic interstitial lung disease or from skin scar tissue. Together these data suggest that both autophagy and NETs are not only involved in inflammation but also in the ensuing fibrosis and thus may represent potential therapeutic targets in human fibrotic diseases.
    The Journal of Pathology 03/2014; · 7.33 Impact Factor
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    ABSTRACT: Background: The survival of patients with malignant pleural effusion is considered generally poor. Most of the studies reporting results of prognostic factors are retrospective, using pleural thoracentesis for diagnosis. The objectives of our study were to reveal possible prognostic factors in patients initially presenting with undiagnosed pleural effusion proven to be malignant by diagnostic thoracoscopy. Methods: Ninety consecutive patients, 48 of whom were male (53%), with a median age of 69 years (range 37-93) and a performance status (PS) of 0/1 (63%) and with initially undiagnosed pleural effusion that was proven to be malignant by thoracoscopy were evaluated. Survival time was defined as the time from thoracoscopic diagnosis to death or the last follow-up. A regression analysis was used to determine significant clinical and biological prognostic factors. Results: Lung carcinoma (44.4%), breast carcinoma (24.4%), and mesothelioma (12.2%) were the most frequent tumors diagnosed. The median overall survival was 11 months (range 0.5-55). The survival of the patients was related to the following factors: histology of the primary tumor (p = 0.008), PS (p < 0.001), white blood cells (p = 0.018), and the blood neutrophil-to-lymphocyte (N/L) ratio (p = 0.002). Multiple regression showed PS, histology, and the N/L ratio. Conclusion: The factors affecting survival in our patients were PS, primary tumor histology, and the N/L ratio. These factors may help physicians select patients for treatment and/or interventional procedures. © 2014 S. Karger AG, Basel.
    Respiration 01/2014; · 2.92 Impact Factor
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    ABSTRACT: To prospectively evaluate the efficacy and safety of a perimeatal-based penile skin flap for neourethral coverage after repair of distal hypospadias with tubularized incised plate urethroplasty (TIPU). In 12 New Zealand white rabbits a ventral urethral defect was created and reconstruction was accomplished with continuous suture. An epithelialized defect-based flap was harvested from the penile skin to cover the repaired defect. The animals were euthanized on the 28th postoperative day and their penises were processed for microscopic examination. In 32 children with distal hypospadias a TIPU was performed. A penile skin flap was created immediately below the distal end of the neourethra and used to cover the urethroplasty. Histological examinations revealed complete restoration of continuity of the stratified squamous epithelium without evidence of inflammation or fistula formation with full consistency with the underlying papillary reticular and corium. There were no cases of fistula formation. One patient developed meatal stenosis. All patients had a satisfactory cosmetic appearance and excellent functional results. The formation of a perimeatal-based skin flap is a simple and safe method of providing additional cover for the constructed neourethra after TIPU, minimizing the fistula rate.
    Journal of pediatric urology 01/2014; · 1.38 Impact Factor
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    ABSTRACT: Introduction. Mucinous adenocarcinoma of the prostate is a rare variant of prostate cancer. Its malignant potential and the clinical course of the affected patients remain, by and large, controversial. No data exist about the course of metastatic mucinous adenocarcinoma of the prostate. Case Presentation. This case report describes the excellent clinical course of a 68-year-old patient with metastatic mucinous adenocarcinoma of the prostate, treated by radical prostatectomy, irradiation, and androgen deprivation. Conclusion. In our case, mucinous adenocarcinoma of the prostate does not appear to behave differently than acinar prostate cancer. Its malignant potential is dependent on its Gleason score.
    Case reports in urology. 01/2014; 2014:218628.
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    ABSTRACT: Squamous carcinoma of the ampulla of Vater is a very rare tumor with only three cases been reported so far. Here, we report the case of a 68-year-old man who presented with painless obstructive jaundice, general fatigue, loss of appetite and weight loss. Laboratory tests revealed hypochromic anemia. Total and direct bilirubin, alkaline phosphatase, liver enzymes, carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) were all elevated. Abdominal ultrasonography and computed tomography showed a distended gallbladder, dilatation of the intra- and extra-hepatic bile ducts and enlargement of the pancreatic head. Endoscopic retrograde cholangiopancreatography revealed a bulging papilla with infiltrative growth at the ampulla of Vater but endoscopic biopsies were inconclusive. The patient was treated with classical Whipple's pancreaticoduodenectomy. Histopathological examination showed a moderately differentiated squamous cell carcinoma. Multiple serial sectioning of the tumor specimen failed to detect an adenomatous component. Regional lymph nodes and resection margins were free of tumor and the disease was classified as stage IIA (T3N0M0) according to the TNM system. Adjuvant treatment was not given. Despite curative resection, multiple liver metastases developed after four months and the patient succumbed to progressive hepatic failure 5 months after the operation. Primary pure squamous cell carcinoma of the ampulla of Vater is a very rare histological type of carcinoma. Clinical characteristics and optimal treatment are obscure. Primary surgical treatment with curative intent should be performed although this type of carcinoma associates with dismal prognosis.
    JOP: Journal of the pancreas 01/2014; 15(1):42-5.
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    ABSTRACT: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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    ABSTRACT: Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is characterised by neutrophil activation. An elevated prevalence of venous thromboembolic events has been reported in AAV. Because of the critical role of neutrophils in inflammation associated thrombosis, we asked whether neutrophil tissue factor (TF) may be implicated in the thrombotic diathesis in AAV. Neutrophils from four patients and sera from 17 patients with ANCA associated vasculitis with active disease and remission were studied. TF expression was assessed by immunoblotting and confocal microscopy. Circulating DNA levels were evaluated. TF expressing microparticles (MPs) were measured by flow cytometry and thrombin-antithrombin complex levels by ELISA. Peripheral blood neutrophils from four patients with active disease expressed elevated TF levels and released TF expressing neutrophil extracellular traps (NETs) and MPs. TF positive NETs were released by neutrophils isolated from the bronchoalveolar lavage and were detected in nasal and renal biopsy specimens. Elevated levels of circulating DNA and TF expressing neutrophil derived MPs were further observed in sera from patients with active disease. Induction of remission attenuated the aforementioned effects. Control neutrophils treated with sera from patients with active disease released TF bearing NETs and MPs which were abolished after IgG depletion. Treatment of control neutrophils with isolated IgG from sera from patients with active disease also resulted in the release of TF bearing NETs. TF implication in MP dependent thrombin generation was demonstrated by antibody neutralisation studies. Expression of TF in NETs and neutrophil derived MPs proposes a novel mechanism for the induction of thrombosis and inflammation in active AAV.
    Annals of the rheumatic diseases 07/2013; · 9.27 Impact Factor
  • Efthimios Sivridis, Alexandra Giatromanolaki
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    ABSTRACT: The endometrial hyperplasias form a spectrum of proliferative lesions, not all of which conform to conventional definition of hyperplasia. For whilst most hyperplastic lesions are composed of cells normally occurring in the late proliferative phase endometrium, there are those few which consist of genuine atypical cells. Lesions of this type, so-called “atypical endometrial hyperplasias”, tend to merge imperceptibly with well differentiated endometrioid adenocarcinomas, giving rise to major challenges: First and foremost, what are the very essential criteria that should be met before diagnosing such a lesion? And what are the very least that should be insisted upon for diagnosing malignancy once an atypical endometrial hyperplasia has been established? What is its true nature and how should ideally be classified? Other less conflicting, but equally interesting, aspects of endometrial hyperplasia which are covered in this account include the conventional hyperplasias, i.e. those lacking cytological atypia, and the overall incidence, risk factors and treatment of the disease. It is worth noting that “pure” stromal cell proliferations are, in itself, not necessarily neoplastic, for many take the form of endometrial stromal hyperplasia.
    Diagnostic Histopathology 07/2013; 19(7):223–230.
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    ABSTRACT: Up-regulation of autophagy provides an important survival mechanism to normal and malignant cells residing in a hypoxic and unfavorable nutritional environment. Yet, its role in the biology of prostate cancer remains poorly understood. In this study we investigated the expression of four major autophagy proteins, namely the microtubule-associated protein 1 light chain 3A (LC3A), LC3B, Beclin 1, and p62, together with an enzyme of anaerobic metabolism, the lactate dehydrogenase 5 (LDH5), in relation to Gleason score and extraprostatic invasion. A series of 96 prostate adenocarcinomas was examined using immunohistochemical techniques and appropriate antibodies. The LC3A protein was expressed in the form of "stone-like" structures, and diffuse cytoplasmic staining, the LC3B reactivity was solely cytoplasmic, whereas that of p62 and LDH5 was both cytoplasmic and nuclear. A median count of 0.90 "stone-like" structures per 200×optical field (range 0-3.6) was highly associated with a high Gleason score. Similarly, a strong cytoplasmic LC3A, LC3B, and p62 expression, when extensive (present in>50% tumor cells per section), was significantly associated with LDH5 and a high Gleason score. In addition, extensive cytoplasmic p62 expression was related with LC3A and B reactivity and also with extraprostatic invasion. Extensive Beclin-1 expression was significantly linked with extraprostatic invasion and also with p62 and LDH5 expression. Immunohistochemical detection of autophagy proteins may potentially prove to be useful as prognostic markers and a tool for the stratification of patients in therapeutic trials targeting autophagy in prostate cancer.
    Urologic Oncology 06/2013; · 3.36 Impact Factor
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    ABSTRACT: Extracellular matrix (ECM) proteins such as fibronectin and collagen III, enzymes such as matrix metalloproteinases and macrophages have been demonstrated to intervene in nasal and paranasal sinuses wound healing. To compare concentration of ECM proteins, enzymes and the recruitment of macrophages during wound repair after monopolar electrocautery in contrast with ultrasound submucosal surgical tissue reduction of inferior nasal turbinate (INT) tested in sheep. Prospective controlled study in sheep. Immunostaining for collagen III, fibronectin, CD68 and matrix metalloproteinase-9 (MMP9) was applied in tissue specimens of INT mucosa after monopolar electrocoagulation (MEC) and ultrasound tissue reduction (UTR). Twelve INTs were studied 1, 3 and 8 weeks post-operatively in each interventional group (MEC and UTR) and 5 INTs were studied in animals of the control group (without surgery). The immunoreactivity was quantitatively graded between 0% to 100% immunoreactivity by a blinded senior pathologist. At the end of the study period collagen III, fibronectin and MMP9 were increased in both groups compared to the levels of the control group. When compared to control group, CD68 immunoreactivity was found higher in MEC group but not in UTR group. Fibronectin subepithelial immunoreactivity exhibited a substantial negative correlation with mucosal epithelial cell necrosis, a substantial positive correlation with fibrosis in MEC-treated specimens and a significant positive correlation with sinusoid engorgement in UTR-treated specimens. Collagen III tissue immunoreactivity showed a particularly significant negative correlation with sinusoid engorgement in MEC-treated specimens. Correlation of fibronectin and collagen III immunoreactivity to histopathologic findings suggests different ECM repair processes between MEC and UTR turbinate tissue reduction. The use of CD68 and MMP9 provides additional clues to the mode of actions of these techniques and to the molecular and cellular events of the nasal mucosa wound healing process.
    Rhinology 06/2013; 51(2):154-61. · 2.78 Impact Factor
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    ABSTRACT: Autophagy is a self-degradation mechanism induced under stress conditions in all eukaryotic cells. Its activity in human lymphomas has not been studied as yet. In this study, the autophagic activity of lymphoid cells was investigated in follicular lymphomas (FL; 48 cases), diffuse large B-cell lymphomas (DLBCL; 78 cases), and in reactive follicular hyperplasias (41 cases), using the light chain 3A (LC3A) antibody and a standard immunohistochemical technique. In all cases, the pattern of LC3A reactivity was uniformly diffuse cytoplasmic, but expressed more frequently in FLs (68.8%) than in DLBCLs (41%) (p=0.02), and much more commonly in DLBCLs than in reactive lymph nodes (24.3%) (p<0.006). Interestingly, FLs expressing LC3A in >10% of lymphoid cells (high reactivity) were associated with the hypoxia-related protein HIF1α and the enzyme of anaerobic metabolism lactate dehydrogenase LDH5 (p=0.004 and p=0.003, respectively). Such associations, however, were not a feature in DLBCLs of increased LC3A activity. LC3A expression in FLs is hypoxia-induced, whereas its expression in DLBCLs may be regulated by other molecular mechanisms. The current study provides a tool for further assessment of autophagic activity in translational and autophagy targeting therapy studies.
    Hematology/ Oncology and Stem Cell Therapy 03/2013; 6(1):20-5.
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    ABSTRACT: A 42-year-old woman undertook a chest radiograph for a routine evaluation prior to surgery for pelvic endometrioma, which revealed a right paratracheal mass slightly displacing the trachea to the left. CT of the thorax disclosed a well demarcated, heterogeneous, lobular, right paratracheal mass, bearing punctate, coarse, and curvilinear calcifications. MRI further revealed two components within the lesion: a larger, cystic, exhibiting thin septations, and a solid component at the lower part exhibiting strong enhancement. No continuity of the mass with the thyroid gland was demonstrated, which had normal size and no focal lesion. Histological examination of the resected mass disclosed lymph node tissue infiltrated by papillary thyroid carcinoma; subsequent total thyroidectomy revealed small foci of papillary carcinoma within both lobes of the thyroid gland. Ablative dose I-131 was administered and the patient was put on daily thyroid supplements.
    General Thoracic and Cardiovascular Surgery 02/2013;
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    ABSTRACT: AIM: The study investigates whether autophagic activity and hypoxia parallel the adenoma-carcinoma sequence. METHOD: The study comprised 120 high-grade dysplasia tubular adenomas with and without morphological features of malignant progression including 22 with questionable evidence of invasion, 37 with definite stromal invasion, 29 with severely dysplastic adenoma, 10 traditional serrated adenomas and 22 classical tubular adenomas lacking aggressive features. The samples were stained immunohistochemically for autophagy (LC3A, Beclin-1) and hypoxia markers (HIF1α). RESULTS: LC3A was detected as diffuse cytoplasmic staining, and as dense "stone-like" structures (SLS) within cytoplasmic vacuoles. Beclin-1 reactivity was purely cytoplasmic, whereas that of HIF1α was both cytoplasmic and nuclear. SLS counts in non-invasive, non-transformed areas of tubular adenomas were consistently low (median SLS 0.5/200x), whereas a progressive increase was noted from areas of equivocal invasion (median 1.3/200x) and intra-mucosal carcinoma (median 1.4/200x) to unequivocal invasive foci (median 2.1/200x) (p<0.0001). A similar association was shown for Beclin-1 and HIF1α expression (p<0.05). Traditional serrated adenomas yielded low SLS counts and weak HIF1α reactivity, but high cytoplasmic LC3A and Beclin-1 expression (p<0.01). CONCLUSION: A hypoxia-driven autophagy in adenomatous polyps, when particularly intense and localized, is commonly associated with early invasion or severely dysplastic adenoma. © 2013 The Authors. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.
    Colorectal Disease 01/2013; · 2.02 Impact Factor

Publication Stats

7k Citations
1,165.61 Total Impact Points


  • 1998–2014
    • Democritus University of Thrace
      • • Α΄ Πανεπιστημιακή Παθολογική Κλινική
      • • Department of Paediatric Surgery
      Komotina, East Macedonia and Thrace, Greece
  • 2013
    • University of Thessaly
      • Department of Pathology
      Lárisa, Thessalia, Greece
  • 2012
    • University of Michigan
      • Life Sciences Institute
      Ann Arbor, MI, United States
  • 1996–2007
    • Oxford University Hospitals NHS Trust
      • Nuffield Department of Clinical Laboratory Sciences
      Oxford, England, United Kingdom
  • 2003
    • University of Leicester
      Leiscester, England, United Kingdom
  • 1998–2001
    • University Hospital of Heraklion
      • Department of Gastroenterology
      Irákleio, Attica, Greece
  • 1995–2000
    • University of Oxford
      Oxford, England, United Kingdom
  • 1999
    • Metaxa Cancer Hospital
      Le Pirée, Attica, Greece
  • 1994
    • Red Cross Hospital, Athens
      Athínai, Attica, Greece