Alexandra Giatromanolaki

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

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Publications (337)1232 Total impact

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    ABSTRACT: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2[4h]) and 24 hours (SF2[24h]) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of γH2AX in PBMC DNA at 0 hours, 30 minutes, and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. The SF2(4h) was inversely correlated with the toxicity grade (P=.006). The γH2AX-ratio(30min) (band density of irradiated/non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative RγH2AX-ratio (γH2AX-ratio(4h)/γH2AX-ratio(30min)) showed a significant direct association with high toxicity grade (P=.01). Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. γH2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low γH2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor γH2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid γH2AX content restoration at 4 hours after irradiation, compatible with efficient DSB repair ability, predicts for increased radiation tolerance. Copyright © 2015 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 04/2015; DOI:10.1016/j.ijrobp.2015.02.023 · 4.18 Impact Factor
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    ABSTRACT: Radiotherapy is an equivalent alternative or complement to radical prostatectomy, with high therapeutic efficacy. High risk patients, however, experience high relapse rates, so that research on radio-sensitization is the most evident route to improve curability of this common disease. In the current study we investigated the autophagic activity in a series of patients with localized prostate tumors treated with radical radiotherapy, using the LC3A and the LAMP2a proteins as markers of autophagosome and lysosome cellular content, respectively. The role of autophagy on prostate cancer cell line resistance to radiation was also examined. Using confocal microscopy on tissue biopsies, we showed that prostate cancer cells have, overall, high levels of LC3A and low levels of LAMP2a compared to normal prostate glands. Tumors with a 'highLC3A/lowLAMP2a' phenotype, suggestive of intensified lysosomal consumption, had a significantly poorer biochemical relapse free survival. The PC3 radioresistant cell line sustained remarkably its autophagic flux ability after radiation, while the DU145 radiosensitive one experiences a prolonged blockage of the autophagic process. This was assessed with aggresome accumulation detection and LC3A/LAMP2a double immunofluorescence, as well as with sequestrosome/p62 protein detection. By silencing the LC3A or LAMP2a expression, both cell lines became more sensitive to escalated doses of radiation. High base line autophagy activity and cell ability to sustain functional autophagy define resistance of prostate cancer cells to radiotherapy. This can be reversed by blocking up-regulated components of the autophagy pathway, which may prove of importance in the field of clinical radiotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.
    Biochemical and Biophysical Research Communications 04/2015; 461(2). DOI:10.1016/j.bbrc.2015.04.014 · 2.28 Impact Factor
  • A. Karpouzis, A. Giatromanolaki, A. Bounovas, E. Sivridis
    Annales de Dermatologie et de Vénéréologie 02/2015; 142(4). DOI:10.1016/j.annder.2014.07.010 · 0.67 Impact Factor
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    ABSTRACT: Aims Neutrophil extracellular traps (NETs) are chromatin filaments released by activated polymorphonuclear neutrophils (PMNs) and decorated with granule proteins with various properties. Several lines of evidence implicate NETs in thrombosis. The functional significance and the in vivo relevance of NETs during atherothrombosis in humans have not been addressed until now. Methods and results Selective sampling of thrombotic material and surrounding blood from the infarct-related coronary artery (IRA) and the non-IRA was performed during primary percutaneous revascularization in 18 patients with ST segment elevation acute myocardial infarction (STEMI). Thrombi isolated from IRA contained PMNs and NETs decorated with tissue factor (TF). Although TF was expressed intracellularly in circulating PMNs of STEMI patients, active TF was specifically exposed by NETs obtained from the site of plaque rupture. Treatment of NET structures with DNase I abolished TF functionality measurement. In vitro treatment of control PMNs with plasma obtained from IRA and non-IRA was further shown to induce intracellular up-regulation of TF but not NET formation. A second step consisting of the interaction between PMNs and thrombin-activated platelets was required for NET generation and subsequent TF exposure. Conclusion The interactionof thrombin-activatedplateletswith PMNs atthe site of plaque rupture during acuteSTEMI resultsin local NET formation and deliveryof active TF. The notion that NETs represent a mechanism by which PMNs release thrombogenic signals during atherothrombosis may offer novel therapeutic targets.
    European Heart Journal 02/2015; DOI:10.1093/eurheartj/ehv007 · 14.72 Impact Factor
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    ABSTRACT: The current study examines the effect of fever-range hyperthermia and mild hypothermia on human cancer cells focusing on cell viability, proliferation and HSP90 expression. A549 and H1299 lung carcinoma, MCF7 breast adenocarcinoma, U87MG and T98G glioblastoma, DU145 and PC3 prostate carcinoma and MRC5 normal fetal lung fibroblasts cell lines were studied. After 3-day exposure to 34°C, 37°C and 40°C, cell viability was determined. Cell proliferation (ki67 index), apoptosis (Caspase 9) and HSP90 expression was studied by confocal microscopy. Viability/proliferation experiments demonstrated that MRC5 fibroblasts were extremely sensitive to hyperthermia, while they were the most resistant to hypothermia. T98G and A549 were thermo-tolerant, the remaining being thermo-sensitive to a varying degree. Nonetheless, as a universal effect, hypothermia reduced viability/proliferation in all cell lines. Hyperthermia sharply induced Caspase 9 in the U87MG most thermo-sensitive cell line. In T98G and A549 thermo-tolerant cell lines, the levels of Caspase 9 declined. Moreover, hyperthermia strongly induced the HSP90 levels in T98G, whilst a sharp decrease was recorded in the thermo-sensitive PC3 and U87MG cell lines. Hyperthermia sensitized thermo-sensitive cancer cell lines to cisplatin and temozolomide, whilst its sensitizing effect was diminished in thermo-tolerant cell lines. The existence of thermo-tolerant and thermo-sensitive cancer cell lines was confirmed, which further encourages research to classify human tumor thermic predilection for patient stratification in clinical trials. Of interest, mild hypothermia had a universal suppressing effect on cancer cell proliferation, further supporting the radio-sensitization hypothesis through reduction of oxygen and metabolic demands.
    PLoS ONE 01/2015; 10(1). DOI:10.1371/journal.pone.0116021 · 3.53 Impact Factor
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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; 15(11). DOI:10.4161/15384047.2014.955719 · 3.63 Impact Factor
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    ABSTRACT: Objectives 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. Methods and Materials Human umbilical vascular endothelial cells (HUVEC) were exposed to 2 Gy of ionizing radiation (IR) and studied using confocal microscopy and western blot analysis, at 4 and 8 days post-irradiation. The role of autophagy flux in HUVEC radio-sensitivity was also examined. Results IR-induced accumulation of LC3A+, LC3B+ and p62 cytoplasmic vacuoles, while in double immunostaining with lysosomal markers (LAMP2a and CathepsinD) repression of the autophagolysosomal flux was evident. Autophagy-related proteins (ATF4, HIF1α., HIF2α, Beclin1) were, however, induced excluding an eventual repressive effect of radiation on autophagy initiating protein expression. Exposure of HUVEC to SMER28, an mTOR-independent inducer of autophagy, enhanced proLC3 and LC3A, B-I protein expression and accelerated the autophagic flux. Pre-treatment of HUVEC with SMER28 protected against the blockage of autophagic flux induced by IR and conferred radio-resistance. Suppression of LC3A/LC3B proteins with siRNAs resulted in radio-sensitization. Conclusions The current data provide a rationale for the development of novel radioprotection policies targeting the autophagic pathway.
    PLoS ONE 07/2014; 9(7):e102408. DOI:10.1371/journal.pone.0102408 · 3.53 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 07/2014; 233(3). DOI:10.1002/path.4359 · 7.33 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; DOI:10.1111/crj.12165 · 2.20 Impact Factor
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    ABSTRACT: Glioblastoma is the most aggressive tumor of central nervous system. Aytophagy is an intracellular pathway that aims at recycling of damaged proteins and organelles via a process of engulfing them in autophagosomes and fusing with lysosomes. The basic proteins that take part in this pathway is LC3A and LC3B (aytophagosomes’ proteins), Lamp2a (lysosomal membrane protein), Cathepsin D (lysosomal protease) and p62 (carries damaged organelles to the autophagosomes). In this study, we investigated the expression pattern of these proteins in normal tissue and two glioblastoma cell lines with Western Blot Analysis. Moreover, we studied the localization of LC3A and LC3B in glioblastoma cells after incubation with Bafilomycin A (late autophagy inhibitor) using confocal microscopy. Finally, we used immunohistochemistry to study the expression pattern of LC3 in cancer cells exposed to various stress factors that simulate tumor environment. Overall, normal brain expressed proLC3A and LC3A-I, but not LC3A-II. This later form was intensively present in U87MG cells and to a lower extent in T98G. In contrast, none of the LC3B forms was expressed in normal brain and T98G cells, whilst an intense expression was evident in U87MG. Moreover, LC3A and B autophagosomes were distinct between them, as confirmed by the lack of co-localization in immunofluorescence, even in the presence of Bafylomycin A. Finally, immunohistochemical findings showed induction of autophagic vesicles and stone-like structures (SLS) in both cancer cell lines under 2DG exposure, but their expression were increased only in U87MG under low pH exposure. All the other autophagic proteins showed the following pattern: a) p62, weak expression in normal brain, intense expression in cancer cell lines, b) Lamp2a, Cathepsin D, intense expression in U87MG cell line, weak expression in T98G cell line and lack of expression in normal tissue.
    EEBE; 05/2014
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    ABSTRACT: Glioblastoma is the most aggressive tumor of central nervous system. Aytophagy is an intracellular pathway that aims at recycling of damaged proteins and organelles via a process of engulfing them in autophagosomes and fusing with lysosomes. The basic proteins that take part in this pathway is LC3A and LC3B (aytophagosomes’ proteins), Lamp2a (lysosomal membrane protein), Cathepsin D (lysosomal protease) and p62 (carries damaged organelles to the autophagosomes). In this study, we investigated the expression pattern of these proteins in normal tissue and two glioblastoma cell lines with Western Blot Analysis. Moreover, we studied the localization of LC3A and LC3B in glioblastoma cells after incubation with Bafilomycin A (late autophagy inhibitor) using confocal microscopy. Finally, we used immunohistochemistry to study the expression pattern of LC3 in cancer cells exposed to various stress factors that simulate tumor environment. Overall, normal brain expressed proLC3A and LC3A-I, but not LC3A-II. This later form was intensively present in U87MG cells and to a lower extent in T98G. In contrast, none of the LC3B forms was expressed in normal brain and T98G cells, whilst an intense expression was evident in U87MG. Moreover, LC3A and B autophagosomes were distinct between them, as confirmed by the lack of co-localization in immunofluorescence, even in the presence of Bafylomycin A. Finally, immunohistochemical findings showed induction of autophagic vesicles and stone-like structures (SLS) in both cancer cell lines under 2DG exposure, but their expression were increased only in U87MG under low pH exposure. All the other autophagic proteins showed the following pattern: a) p62, weak expression in normal brain, intense expression in cancer cell lines, b) Lamp2a, Cathepsin D, intense expression in U87MG cell line, weak expression in T98G cell line and lack of expression in normal tissue.
    EEBE, Ioannina; 05/2014
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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. DOI:10.1007/s12032-014-0945-0 · 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 04/2014; 110(9). DOI:10.1038/bjc.2014.196 · 4.82 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 04/2014; 110(9). DOI:10.1038/bjc.2014.158 · 4.82 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.
    01/2014; 2014:218628. DOI:10.1155/2014/218628
  • Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A181-A181. DOI:10.1136/annrheumdis-2013-eular.579 · 9.27 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; 87(4). DOI:10.1159/000356764 · 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; 10(3). DOI:10.1016/j.jpurol.2013.12.010 · 1.41 Impact Factor
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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.

Publication Stats

8k Citations
1,232.00 Total Impact Points

Institutions

  • 2000–2015
    • Democritus University of Thrace
      • • School of Medicine
      • • Α΄ Πανεπιστημιακή Παθολογική Κλινική
      • • Κλινική Παιδοχειρουργικής
      Komotina, East Macedonia and Thrace, 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
      • • Molecular Oncology Laboratory
      Oxford, England, United Kingdom
    • Saint Savvas Hospital
      Athínai, Attica, Greece
  • 2003
    • University of Leicester
      Leiscester, England, United Kingdom
  • 1998–2000
    • University Hospital of Heraklion
      • Department of Gastroenterology
      Irákleio, Attica, Greece
  • 1995–1999
    • University of Oxford
      Oxford, England, United Kingdom
  • 1994
    • Red Cross Hospital, Athens
      Athínai, Attica, Greece