Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Anastasios D. Giannou is active.

Publication


Featured researches published by Anastasios D. Giannou.


Journal of Clinical Investigation | 2015

Mast cells mediate malignant pleural effusion formation

Anastasios D. Giannou; Antonia Marazioti; Magda Spella; Nikolaos Kanellakis; Hara Apostolopoulou; Ioannis Psallidas; Zeljko M. Prijovich; Malamati Vreka; Dimitra Zazara; Ioannis Lilis; Vassilios Papaleonidopoulos; Chrysoula A. Kairi; Alexandra L. Patmanidi; Ioanna Giopanou; Nikolitsa Spiropoulou; Vaggelis Harokopos; Vassilis Aidinis; Dionisios Spyratos; Stamatia Teliousi; Helen Papadaki; Stavros Taraviras; Linda A. Snyder; Oliver Eickelberg; Dimitrios Kardamakis; Yoichiro Iwakura; Thorsten B. Feyerabend; Hans Reimer Rodewald; Ioannis Kalomenidis; Timothy S. Blackwell; Theodora Agalioti

Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1β, which in turn induced pleural vasculature leakiness and triggered NF-κB activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell-induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenocarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable.


PLOS ONE | 2013

Beneficial Impact of CCL2 and CCL12 Neutralization on Experimental Malignant Pleural Effusion

Antonia Marazioti; Chrysoula A. Kairi; Magda Spella; Anastasios D. Giannou; Sophia Magkouta; Ioanna Giopanou; Vassilios Papaleonidopoulos; Ioannis Kalomenidis; Linda A. Snyder; Dimitrios Kardamakis; Georgios T. Stathopoulos

Using genetic interventions, we previously determined that C-C motif chemokine ligand 2 (CCL2) promotes malignant pleural effusion (MPE) formation in mice. Here we conducted preclinical studies aimed at assessing the specific therapeutic potential of antibody-mediated CCL2 blockade against MPE. For this, murine MPEs or skin tumors were generated in C57BL/6 mice by intrapleural or subcutaneous delivery of lung (LLC) or colon (MC38) adenocarcinoma cells. Human lung adenocarcinoma cells (A549) were used to induce MPEs in severe combined immunodeficient mice. Intraperitoneal antibodies neutralizing mouse CCL2 and/or CCL12, a murine CCL2 ortholog, were administered at 10 or 50 mg/kg every three days. We found that high doses of CCL2/12 neutralizing antibody treatment (50 mg/kg) were required to limit MPE formation by LLC cells. CCL2 and CCL12 blockade were equally potent inhibitors of MPE development by LLC cells. Combined CCL2 and CCL12 neutralization was also effective against MC38-induced MPE and prolonged the survival of mice in both syngeneic models. Mouse-specific CCL2-blockade limited A549-caused xenogeneic MPE, indicating that host-derived CCL2 also contributes to MPE precipitation in mice. The impact of CCL2/12 antagonism was associated with inhibition of immune and vascular MPE-related phenomena, such as inflammation, new blood vessel assembly and plasma extravasation into the pleural space. We conclude that CCL2 and CCL12 blockade are effective against experimental MPE induced by murine and human adenocarcinoma in mice. These results suggest that CCL2-targeted therapies may hold promise for future use against human MPE.


Nature Communications | 2017

Mutant KRAS promotes malignant pleural effusion formation

Theodora Agalioti; Anastasios D. Giannou; Anthi Krontira; Nikolaos Kanellakis; Danai Kati; Malamati Vreka; Mario Pepe; Magda Spella; Ioannis Lilis; Dimitra Zazara; Eirini Nikolouli; Nikolitsa Spiropoulou; Andreas Papadakis; Konstantina Papadia; Apostolos Voulgaridis; Vaggelis Harokopos; Panagiota Stamou; Silke Meiners; Oliver Eickelberg; Linda A. Snyder; Sophia G. Antimisiaris; Dimitrios Kardamakis; Ioannis Psallidas; Antonia Marazioti; Georgios T. Stathopoulos

Malignant pleural effusion (MPE) is the lethal consequence of various human cancers metastatic to the pleural cavity. However, the mechanisms responsible for the development of MPE are still obscure. Here we show that mutant KRAS is important for MPE induction in mice. Pleural disseminated, mutant KRAS bearing tumour cells upregulate and systemically release chemokine ligand 2 (CCL2) into the bloodstream to mobilize myeloid cells from the host bone marrow to the pleural space via the spleen. These cells promote MPE formation, as indicated by splenectomy and splenocyte restoration experiments. In addition, KRAS mutations are frequently detected in human MPE and cell lines isolated thereof, but are often lost during automated analyses, as indicated by manual versus automated examination of Sanger sequencing traces. Finally, the novel KRAS inhibitor deltarasin and a monoclonal antibody directed against CCL2 are equally effective against an experimental mouse model of MPE, a result that holds promise for future efficient therapies against the human condition.


Embo Molecular Medicine | 2017

NRAS destines tumor cells to the lungs

Anastasios D. Giannou; Antonia Marazioti; Nikolaos Kanellakis; Ioanna Giopanou; Ioannis Lilis; Dimitra Zazara; Giannoula Ntaliarda; Danai Kati; Vasileios Armenis; Georgia Giotopoulou; Anthi Krontira; Marina Lianou; Theodora Agalioti; Malamati Vreka; Maria Papageorgopoulou; Sotirios Fouzas; Dimitrios Kardamakis; Ioannis Psallidas; Magda Spella; Georgios T. Stathopoulos

The lungs are frequently affected by cancer metastasis. Although NRAS mutations have been associated with metastatic potential, their exact role in lung homing is incompletely understood. We cross‐examined the genotype of various tumor cells with their ability for automatic pulmonary dissemination, modulated NRAS expression using RNA interference and NRAS overexpression, identified NRAS signaling partners by microarray, and validated them using Cxcr1‐ and Cxcr2‐deficient mice. Mouse models of spontaneous lung metastasis revealed that mutant or overexpressed NRAS promotes lung colonization by regulating interleukin‐8‐related chemokine expression, thereby initiating interactions between tumor cells, the pulmonary vasculature, and myeloid cells. Our results support a model where NRAS‐mutant, chemokine‐expressing circulating tumor cells target the CXCR1‐expressing lung vasculature and recruit CXCR2‐expressing myeloid cells to initiate metastasis. We further describe a clinically relevant approach to prevent NRAS‐driven pulmonary metastasis by inhibiting chemokine signaling. In conclusion, NRAS promotes the colonization of the lungs by various tumor types in mouse models. IL‐8‐related chemokines, NRAS signaling partners in this process, may constitute an important therapeutic target against pulmonary involvement by cancers of other organs.


European Journal of Pharmaceutical Sciences | 2017

Multifunctional LUV liposomes decorated for BBB and amyloid targeting - B. In vivo brain targeting potential in wild-type and APP/PS1 mice

Konstantina Papadia; Anastasios D. Giannou; Eleni Markoutsa; Christian Bigot; Greejte Vanhoute; Spyridon Mourtas; Annemie Van der Linded; Georgios T. Stathopoulos; Sophia G. Antimisiaris

&NA; Multifunctional liposomes (mf‐LIPs) having a curcumin‐lipid ligand (to target amyloids) together with two ligands to target the transferrin, and the low‐density apolipoprotein receptor of the blood‐brain‐barrier (BBB) on their surface, were previously studied (in vitro) as potential theranostic systems for Alzheimers disease (AD) (Papadia et al., 2017, Eur. J. Pharm. Sciences; 101:140–148). Herein, the targeting potential of mf‐LIPs was compared to that of BBB‐LIPs (liposomes having only the two BBB‐specific ligands) in FVB mice (normal), as well as in double transgenic mice (APP/PS1) and their corresponding littermates (WT), by live‐animal (in vivo) and explanted organ (ex vivo) imaging. In FVB mice, the head‐signals of mf‐LIPs and BBB‐LIPs are either similar, or signals from mf‐LIP are higher, suggesting that the co‐presence of the curcumin derivative on the liposome surface does not disturb the functionality of the BBB‐specific ligands. Higher brain / liver + spleen ratios (ex vivo) were calculated post‐injection of mf‐LIP, compared to those found after BBB‐LIP injection, due to the reduced distribution of mf‐LIPs in the liver and spleen; showing that the curcumin ligand increases the stealth properties of liposomes by reducing their uptake by liver and spleen. The later effect is more pronounced when the density of the BBB‐specific ligands on the mf‐LIPs is 0.1 mol%, compared to 0.2%, highlighting the importance of this parameter. When a high lipid dose (4 mg/mouse) is injected in WT and APP/PS1 mice, the head‐signals of mf‐LIPs are significantly higher than those of BBB‐LIPs, but no differences are observed between WT and APP/PS1 mice. However, after administration of a low liposome dose (0.05 mg/mouse) of mf‐LIPs, significant differences in the head‐signals are found between WT and transgenic mice, highlighting the AD theranostic potential of the multifunctional liposomes, as well as the importance of the experimental parameters used in such in vivo screening studies. Graphical abstract Figure. No caption available.


Journal of Thoracic Disease | 2015

Switching off malignant pleural effusion formation—fantasy or future?

Magda Spella; Anastasios D. Giannou; Georgios T. Stathopoulos

Malignant pleural effusion (MPE) is common and difficult to treat. In the vast majority of patients the presence of MPE heralds incurable disease, associated with poor quality of life, morbidity and mortality. Current therapeutic approaches are inefficient and merely offer palliation of associated symptoms. Recent scientific progress has shed light in the biologic processes governing the mechanisms behind the pathobiology of MPE. Pleural based tumors interfere with pleural fluid drainage, as well as the host vasculature and immune system, resulting in decreased fluid absorption and increased pleural fluid production via enhanced plasma extravasation into the pleural space. In order to achieve this feat, pleural based tumors must elicit critical vasoactive events in the pleura, thus forming a favorable microenvironment for tumor dissemination and MPE development. Such properties involve specific transcriptional signaling cascades in addition to secretion of important mediators which attract and activate host cell populations which, in turn, impact tumor cell functions. The dissection of the biologic steps leading to MPE formation provides novel therapeutic targets and recent research findings provide encouraging results towards future therapeutic innovations in MPE management.


Nature Communications | 2018

Myeloid-derived interleukin-1β drives oncogenic KRAS -NF-κΒ addiction in malignant pleural effusion

Antonia Marazioti; Ioannis Lilis; Malamati Vreka; Hara Apostolopoulou; Argyro Kalogeropoulou; Ioanna Giopanou; Georgia Giotopoulou; Anthi Krontira; Marianthi Iliopoulou; Nikolaos Kanellakis; Theodora Agalioti; Anastasios D. Giannou; Celestial Jones-Paris; Yoichiro Iwakura; Dimitrios Kardamakis; Timothy S. Blackwell; Stavros Taraviras; Magda Spella; Georgios T. Stathopoulos

Malignant pleural effusion (MPE) is a frequent metastatic manifestation of human cancers. While we previously identified KRAS mutations as molecular culprits of MPE formation, the underlying mechanism remained unknown. Here, we determine that non-canonical IKKα-RelB pathway activation of KRAS-mutant tumor cells mediates MPE development and this is fueled by host-provided interleukin IL-1β. Indeed, IKKα is required for the MPE-competence of KRAS-mutant tumor cells by activating non-canonical NF-κB signaling. IL-1β fuels addiction of mutant KRAS to IKKα resulting in increased CXCL1 secretion that fosters MPE-associated inflammation. Importantly, IL-1β-mediated NF-κB induction in KRAS-mutant tumor cells, as well as their resulting MPE-competence, can only be blocked by co-inhibition of both KRAS and IKKα, a strategy that overcomes drug resistance to individual treatments. Hence we show that mutant KRAS facilitates IKKα-mediated responsiveness of tumor cells to host IL-1β, thereby establishing a host-to-tumor signaling circuit that culminates in inflammatory MPE development and drug resistance.Malignant pleural effusion (MPE) is a life-threatening cancer-related disorder. Here, the authors show that KRAS-mutant tumor cells require IKKα, activated via host-provided IL-1β, to promote MPE development and that co-inhibition of both KRAS and IKKα ameliorates the development of MPE in mouse models.


Thorax | 2016

S7 Mouse lung adenocarcinoma cell lines reveal PRL2C2 as a novel lung tumour promoter

Nikolaos Kanellakis; Anastasios D. Giannou; M Pepe; Theodora Agalioti; Dimitra Zazara; Malamati Vreka; Ioannis Lilis; Ioanna Giopanou; Magdalini Spella; Antonia Marazioti; Najib M. Rahman; Ian D. Pavord; Ioannis Psallidas; Georgios T. Stathopoulos

Background Carcinogen-inflicted human cancers, including lung tumours harbour thousands of mutations per genome, most of which are unknown (Garraway, LA et al, Cell 2013;153:17–37). Aim To develop a faithful mouse model of human tobacco carcinogen-induced lung adenocarcinoma suitable for the identification of novel oncogenic genes and pathways. Methods We repeatedly managed to obtain several murine lung adenocarcinoma cell lines (MLA) by chronically exposing various mouse strains to different tobacco carcinogens. MLA were characterised for cancer stemness and oncogenes, as well as global gene expression. Results To date, 12 MLA cell lines have been derived from Wt and transgenic mice on the FVB, Balb/c, and C57BL/6 strains by means of urethane or diethylnitrosamine exposure. All MLA were immortal, phenotypically stable, and indefinitely passaged in vitro over a period of over 18 months and/or 60 passages. In addition, all cell lines were oncogenic, transplantable, metastatic, and uniformly lethal in vivo. Interestingly, MLA displayed Kras mutations in codon 61, mono- or bi-allelic Trp53 loss, and expression of lung cancer stemness factors Itgb3 and Lgr6, in amazing similarity to human lung cancers. Microarray revealed that all MLA cell lines heavily overexpressed Prl2c2, encoding proliferin, in comparison to the native lungs. Prl2c2 silencing diminished MLA proliferation and stemness, to a degree comparable with Itgb3 interference. Conclusions MLA are faithful models of human lung adenocarcinoma that led to the discovery of Prl2c2 as a candidate lung tumour promoter. Funding European Research Council Starting Independent Investigator Grant #260524. Respire 2 European Respiratory Society Fellowship, European Respiratory Society Short Term Research Fellowship.


Thorax | 2016

S8 Osteopontin as an airway epithelial tumour promoter

Ioannis Psallidas; Nikolaos Kanellakis; Malamati Vreka; Anastasios D. Giannou; L Maniatis; Charalampos Moschos; Ioanna Giopanou; Theodora Agalioti; Ioannis Lilis; Sophia Magkouta; Ioannis Kalomenidis; Najib M. Rahman; Ian D. Pavord; Georgios T. Stathopoulos

Osteopontin (secreted phosphoprotein 1; SPP1) expression has been identified in human lung cancer and has been linked with enhanced tumour progression. To examine its functional role, we induced lung tumours by repetitive urethane or MCA/BHT lung carcinogens in C57BL/6 mice lacking both (Spp1-/-), one (Spp1+/-), or no (Spp1+/+) copy of the endogenous Spp1 gene. Primary end-points were lung tumour number and size; secondary end-points were SPP1 expression, epithelial cell survival, carcinogen-induced inflammation, and angiogenesis. Data are presented as mean ± SD. Compared with Spp1+/+ mice (n = 22), Spp1-/- mice (n = 25) developed dramatically fewer and significantly smaller lung tumours in response to urethane, while Spp1± mice (n = 12) behaved similar to Spp1-/- mice (number/diameter of lung tumours in Spp1+/+, Spp1+/-, and Spp1-/- mice, respectively: 16.1 ± 12.7/1.2 ± 0.3 mm, 2.4 ± 2.3/0.9 ± 0.2 mm, and 1.3 ± 1.6/0.7 ± 0.2 mm; P < 0.05 for comparison of Spp1+/+ with Spp1-/- and Spp1+/- mice). Spp1-/- mice were also protected from two-hit MCA/BHT-oncogenesis compared with Spp1+/+ controls. Spp1-/- mice displayed decreased epithelial cell survival and reduced numbers of airspace macrophages early after urethane, and enhanced tumour cell apoptosis and limited tumour angiogenesis at late stages of lung tumour progression. SPP1 was expressed in the naïve lung by non-ciliated airway epithelial cells and alveolar macrophages and was significantly up-regulated during multi-stage lung carcinogenesis. Our data indicate that SPP1 is functionally involved in airway epithelial carcinogenesis and may present a target for lung cancer treatment and prevention.


Journal of Thoracic Disease | 2015

Pleural involvement in lung cancer

Theodora Agalioti; Anastasios D. Giannou; Georgios T. Stathopoulos

Collaboration


Dive into the Anastasios D. Giannou's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge