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3. Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming

Author

Pateras, Ioannis S., Williams, Chloe, Gianniou, Despoina D., Margetis, Aggelos T., Avgeris, Margaritis, Rousakis, Pantelis, Legaki, Aigli-Ioanna, Mirtschink, Peter, Zhang, Wei, Panoutsopoulou, Konstantina, Delis, Anastasios D., Pagakis, Stamatis N., Tang, Wei, Ambs, Stefan, Warpman Berglund, Ulrika, Helleday, Thomas, Varvarigou, Anastasia, Chatzigeorgiou, Antonios, Nordström, Anders, Tsitsilonis, Ourania E., Trougakos, Ioannis P., Gilthorpe, Jonathan D., and Frisan, Teresa

Published
2023
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4. Integrated omics analysis for characterization of the contribution of high fructose corn syrup to non-alcoholic fatty liver disease in obesity

Author

Papadopoulos, Grigorios, Legaki, Aigli-Ioanna, Georgila, Konstantina, Vorkas, Panagiotis, Giannousi, Eirini, Stamatakis, George, Moustakas, Ioannis I., Petrocheilou, Maria, Pyrina, Iryna, Gercken, Bettina, Kassi, Eva, Chavakis, Triantafyllos, Pateras, Ioannis S., Panayotou, George, Gika, Helen, Samiotaki, Martina, Eliopoulos, Aristides G., and Chatzigeorgiou, Antonios

Published
2023
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6. Author Correction: Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability

Author

Galanos, Panagiotis, Pappas, George, Polyzos, Alexander, Kotsinas, Athanassios, Svolaki, Ioanna, Giakoumakis, Nickolaos N., Glytsou, Christina, Pateras, Ioannis S., Swain, Umakanta, Souliotis, Vassilis L., Georgakilas, Alexandros G., Geacintov, Nicholas, Scorrano, Luca, Lukas, Claudia, Lukas, Jiri, Livneh, Zvi, Lygerou, Zoi, Chowdhury, Dipanjan, Sørensen, Claus Storgaard, Bartek, Jiri, and Gorgoulis, Vassilis G.

Published
2022
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7. Pancreatic Cancer and Its Correlation with Embryogenesis: Identification of Biomolecular Markers Using Machine Learning Methods

Author

Torakis, Ioannis, Bei, Ekaterini S., Sfakianakis, Stelios, Pateras, Ioannis S., Zervakis, Michalis, Magjarevic, Ratko, Series Editor, Ładyżyński, Piotr, Associate Editor, Ibrahim, Fatimah, Associate Editor, Lackovic, Igor, Associate Editor, Rock, Emilio Sacristan, Associate Editor, Jarm, Tomaz, editor, Cvetkoska, Aleksandra, editor, Mahnič-Kalamiza, Samo, editor, and Miklavcic, Damijan, editor

Published
2021
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8. Helicobacter pylori Eradication Reverses DNA Damage Response Pathway but Not Senescence in Human Gastric Epithelium

Author

Kalisperati, Polyxeni, primary, Spanou, Evangelia, additional, Pateras, Ioannis S., additional, Evangelou, Konstantinos, additional, Thymara, Irene, additional, Korkolopoulou, Penelope, additional, Kotsinas, Athanassios, additional, Vlachoyiannopoulos, Panayiotis G., additional, Tzioufas, Athanasios G., additional, Kanellopoulos, Christos, additional, Gorgoulis, Vassilis G., additional, and Sougioultzis, Stavros, additional

Published
2024
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11. Diagnostic challenges during inflammation and cancer : current biomarkers and future perspectives in navigating through the minefield of reactive versus dysplastic and cancerous lesions in the digestive system

Author

Pateras, Ioannis S., Igea, Ana, Nikas, Ilias P., Leventakou, Danai, Koufopoulos, Nektarios I., Ieronimaki, Argyro Ioanna, Bergonzini, Anna, Ryu, Han Suk, Chatzigeorgiou, Antonios, Frisan, Teresa, Kittas, Christos, Panayiotides, Ioannis G., Pateras, Ioannis S., Igea, Ana, Nikas, Ilias P., Leventakou, Danai, Koufopoulos, Nektarios I., Ieronimaki, Argyro Ioanna, Bergonzini, Anna, Ryu, Han Suk, Chatzigeorgiou, Antonios, Frisan, Teresa, Kittas, Christos, and Panayiotides, Ioannis G.

Abstract

In the setting of pronounced inflammation, changes in the epithelium may overlap with neoplasia, often rendering it impossible to establish a diagnosis with certainty in daily clinical practice. Here, we discuss the underlying molecular mechanisms driving tissue response during persistent inflammatory signaling along with the potential association with cancer in the gastrointestinal tract, pancreas, extrahepatic bile ducts, and liver. We highlight the histopathological challenges encountered in the diagnosis of chronic inflammation in routine practice and pinpoint tissue-based biomarkers that could complement morphology to differentiate reactive from dysplastic or cancerous lesions. We refer to the advantages and limitations of existing biomarkers employing immunohistochemistry and point to promising new markers, including the generation of novel antibodies targeting mutant proteins, miRNAs, and array assays. Advancements in experimental models, including mouse and 3D models, have improved our understanding of tissue response. The integration of digital pathology along with artificial intelligence may also complement routine visual inspections. Navigating through tissue responses in various chronic inflammatory contexts will help us develop novel and reliable biomarkers that will improve diagnostic decisions and ultimately patient treatment.

Published
2024
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12. Genotoxin-producing Salmonella enterica induces tissue-specific types of DNA damage and DNA damage response outcomes

Author

Chiloeches, Maria Lopez, Bergonzini, Anna, Martin, Océane C. B., Bergstein, Nicole, Erttmann, Saskia F., Aung, Kyaw Min, Gekara, Nelson O., Cariño, Javier F. Avila, Pateras, Ioannis S., Frisan, Teresa, Chiloeches, Maria Lopez, Bergonzini, Anna, Martin, Océane C. B., Bergstein, Nicole, Erttmann, Saskia F., Aung, Kyaw Min, Gekara, Nelson O., Cariño, Javier F. Avila, Pateras, Ioannis S., and Frisan, Teresa

Abstract

Introduction: Typhoid toxin-expressing Salmonella enterica causes DNA damage in the intestinal mucosa in vivo, activating the DNA damage response (DDR) in the absence of inflammation. To understand whether the tissue microenvironment constrains the infection outcome, we compared the immune response and DDR patterns in the colon and liver of mice infected with a genotoxigenic strain or its isogenic control strain. Methods: In situ spatial transcriptomic and immunofluorescence have been used to assess DNA damage makers, activation of the DDR, innate immunity markers in a multiparametric analysis. Result: The presence of the typhoid toxin protected from colonic bacteria-induced inflammation, despite nuclear localization of p53, enhanced co-expression of type-I interferons (IfnbI) and the inflammasome sensor Aim2, both classic features of DNA-break-induced DDR activation. These effects were not observed in the livers of either infected group. Instead, in this tissue, the inflammatory response and DDR were associated with high oxidative stress-induced DNA damage. Conclusions: Our work highlights the relevance of the tissue microenvironment in enabling the typhoid toxin to suppress the host inflammatory response in vivo.

Published
2024
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13. The "Forgotten" Subtypes of Breast Carcinoma: A Systematic Review of Selected Histological Variants Not Included or Not Recognized as Distinct Entities in the Current World Health Organization Classification of Breast Tumors.

Author

Koufopoulos, Nektarios I., Boutas, Ioannis, Pouliakis, Abraham, Samaras, Menelaos G., Kotanidis, Christakis, Kontogeorgi, Adamantia, Dimas, Dionysios T., Ieronimaki, Argyro-Ioanna, Leventakou, Danai, Spathis, Aris, Zanelli, Magda, Palicelli, Andrea, Zizzo, Maurizio, Goutas, Dimitrios, Pateras, Ioannis S., and Panayiotides, Ioannis G.

Subjects
CELL differentiation, CANCER patients, BREAST tumors, TUMOR classification, CARCINOMA, BREAST
Abstract

Breast carcinoma is the most common cancer in women. Nineteen different subtypes of breast carcinomas are recognized in the current WHO classification of breast tumors. Except for these subtypes, there are a number of carcinomas with special morphologic and immunohistochemical features that are not included in the 5th WHO classification, while others are considered special morphologic patterns of invasive breast carcinoma of no special type. In this manuscript, we systematically review the literature on four different subtypes of invasive breast carcinoma, namely lymphoepithelioma-like breast carcinoma, breast carcinoma with osteoclast-like giant cells, signet-ring breast carcinoma, and metaplastic breast carcinoma with melanocytic differentiation. We describe their clinicopathological characteristics, focusing on the differential diagnosis, treatment, and prognosis. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Pre-Existing Immunity Predicts Response to First-Line Immunotherapy in Non-Small Cell Lung Cancer Patients.

Author

Xagara, Anastasia, Goulielmaki, Maria, Fortis, Sotirios P., Kokkalis, Alexandros, Chantzara, Evangelia, Christodoulopoulos, George, Samaras, Ioannis, Saloustros, Emmanouil, Tsapakidis, Konstantinos, Papadopoulos, Vasileios, Pateras, Ioannis S., Georgoulias, Vasilis, Baxevanis, Constantin N., and Kotsakis, Athanasios

Subjects
IMMUNOPHENOTYPING, IN vitro studies, IMMUNOSUPPRESSIVE agents, RESEARCH funding, IMMUNOTHERAPY, ANTINEOPLASTIC agents, PROGRAMMED death-ligand 1, TUMOR markers, DESCRIPTIVE statistics, MYELOID-derived suppressor cells, IMMUNE checkpoint inhibitors, ANTIGENS, LUNG cancer, IMMUNITY, OVERALL survival
Abstract

Simple Summary: The content as well as the status of immune cells before immunotherapy administration are indispensable for response. TAA-specific T cells have been associated with poor responses to chemotherapy. However, their role as predictive biomarkers for immunotherapy administration as well as their interplay with other immune system cells is not well understood. Our findings reveal that combined analysis of pre-existing immunity T cells of different immune parameters in treatment-naïve NSCLC patients leads to better prediction tools for immunotherapy response. T-cell-mediated anti-tumoral responses may have significant clinical relevance as a biomarker for response to immunotherapy. The value of peripheral blood pre-existing tumor antigen-specific T cells (PreI+) as a predictive immunotherapy biomarker in NSCLC patients was investigated, along with the frequency of various circulating immune cells. Fifty-two treatment-naïve, stage III/IV NSCLC patients, treated with front-line immune checkpoint inhibitors (ICI)-containing regimens were enrolled. PreI was calculated as the percentages of CD3+IFNγ+ cells after in vitro co-cultures of PBMCs with peptides against four different Tumor-Associated Antigens (TAA). Immunophenotyping of peripheral blood immune cells was performed using multicolor flow cytometry. PreI+ T cells were detected in 44% of patients. Median overall survival (OS) was significantly higher in PreI+ patients compared to PreI– patients (not reached vs. 321 days, respectively; p = 0.014). PreI+ patients had significantly higher numbers of possible exhausted CD3+CD8+PD-1+ cells and lower percentages of immunosuppressive Tregs compared to PreI− patients. Additionally, patients with PreI+ and low numbers of peripheral blood M-MDSCs had a significant survival advantage compared to the rest of the patients. Thus, combining pre-existing tumor antigen-specific immunity before initiation of ICI in NSCLC patients with selected immune-suppressive cells could identify patients who have a favorable clinical outcome when treated with ICI-containing regimens. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Diagnostic Challenges during Inflammation and Cancer: Current Biomarkers and Future Perspectives in Navigating through the Minefield of Reactive versus Dysplastic and Cancerous Lesions in the Digestive System

Author

Pateras, Ioannis S., primary, Igea, Ana, additional, Nikas, Ilias P., additional, Leventakou, Danai, additional, Koufopoulos, Nektarios I., additional, Ieronimaki, Argyro Ioanna, additional, Bergonzini, Anna, additional, Ryu, Han Suk, additional, Chatzigeorgiou, Antonios, additional, Frisan, Teresa, additional, Kittas, Christos, additional, and Panayiotides, Ioannis G., additional

Published
2024
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16. Correction to: A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence

Author

Komseli, Eirini-Stavroula, Pateras, Ioannis S., Krejsgaard, Thorbjørn, Stawiski, Konrad, Rizou, Sophia V., Polyzos, Alexander, Roumelioti, Fani-Marlen, Chiourea, Maria, Mourkioti, Ioanna, Paparouna, Eleni, Zampetidis, Christos P., Gumeni, Sentiljana, Trougakos, Ioannis P., Pefani, Dafni-Eleftheria, O’Neill, Eric, Gagos, Sarantis, Eliopoulos, Aristides G., Fendler, Wojciech, Chowdhury, Dipanjan, Bartek, Jiri, and Gorgoulis, Vassilis G.

Published
2021
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17. A Functional Immune System Is Required for the Systemic Genotoxic Effects of Localized Irradiation

Author

Lobachevsky, Pavel N., Ventura, Jessica, Giannakandropoulou, Lina, Forrester, Helen, Palazzolo, Jason S., Haynes, Nicole M., Stevenson, Andrew W., Hall, Christopher J., Mason, Joel, Pollakis, Gerasimos, Pateras, Ioannis S., Gorgoulis, Vassilis, Terzoudi, Georgia I., Hamilton, John A., Sprung, Carl N., Georgakilas, Alexandros G., and Martin, Olga A.

Published
2019
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18. Malignant Brenner Tumor of the Ovary: A Systematic Review of the Literature.

Author

Koufopoulos, Nektarios I., Pouliakis, Abraham, Samaras, Menelaos G., Kotanidis, Christakis, Boutas, Ioannis, Kontogeorgi, Adamantia, Dimas, Dionysios, Sitara, Kyparissia, Zacharatou, Andriani, Ieronimaki, Argyro-Ioanna, Spathis, Aris, Leventakou, Danai, Zanelli, Magda, Pateras, Ioannis S., Panayiotides, Ioannis G., Palicelli, Andrea, and Syrios, John

Subjects
LYMPHADENECTOMY, RESEARCH funding, DESCRIPTIVE statistics, SYMPTOMS, BRENNER tumors, SYSTEMATIC reviews, MEDLINE, ONLINE information services, TUMOR antigens, OVARIES
Abstract

Simple Summary: Malignant Brenner tumors are rare ovarian neoplasms. Our aim is to provide insights concerning this rare entity. We reviewed 115 cases reported in the English literature until 15 September 2023, and analyzed the available demographic, clinical, and pathologic data. We also described the treatment modalities. A comparison of the available data showed that patients treated with lymph node dissection had a better disease-related survival rate. Disease recurrence was associated with tumor stage with marginal statistical significance and was more frequent in patients with ascites and those with abnormal CA-125 levels. Larger series with treatment details and long term follow-up data are needed to define the optimal management for this uncommon entity. Background: Malignant Brenner tumors are rare ovarian tumors, accounting for less than 1% of malignant ovarian neoplasms. The aim of this manuscript is to systematically review the current literature concerning malignant Brenner tumors. Methods: We searched three medical databases (PubMed, Scopus, and Web of Science) for relevant articles published until 15 September 2023. Results: After applying inclusion and exclusion criteria, 48 manuscripts describing 115 cases were included in this study from the English literature. Conclusions: We analyzed the demographic, clinical, pathological, and oncological characteristics of 115 patients with malignant Brenner tumors. The statistical analysis showed that recurrence was marginally statistically significantly related to tumor stage and was more common in patients with ascites and in women with abnormal CA-125 levels; patients that were treated with lymphadenectomy had better disease-specific survival. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Human Papillomavirus 16 DNA Methylation Patterns and Investigation of Integration Status in Head and Neck Cancer Cases

Author

Zygouras, Ioannis, primary, Leventakou, Danai, additional, Pouliakis, Abraham, additional, Panagiotou, Styliana, additional, Tsakogiannis, Dimitris, additional, Konstantopoulos, Georgios, additional, Logotheti, Eirini, additional, Samaras, Menelaos, additional, Kyriakopoulou, Zaharoula, additional, Beloukas, Apostolos, additional, Pateras, Ioannis S., additional, Delides, Alexandros, additional, Psyrri, Amanda, additional, Panayiotides, Ioannis G., additional, Yiangou, Minas, additional, and Kottaridi, Christine, additional

Published
2023
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22. Conditioning attenuates kidney and heart injury in rats following transient suprarenal occlusion of the abdominal aorta

Author

Karageorgiadi, Dimitra M., Tsilimigras, Diamantis I., Selemenakis, Platonas, Vlachou, Vassiliki, de Lastic, Anne-Lise, Rodi, Maria, Chatziathanasiou, Danai, Savvatakis, Konstantinos, Antoniou, Nikolaos, Deli, Aikaterini C., Papalampros, Alexandros, Filis, Konstantinos A., Mouzaki, Athanasia, Varvarigou, Anastasia, Zografos, George, Gorgoulis, Vassilis G., Pateras, Ioannis S., and Sigala, Fragiska

Published
2020
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25. Abstract CT182: OXC-101 shows favorable safety profile in first in human phase 1 trial in patients with advanced solid cancer

Author

Yachnin, Jeffrey, primary, Ny, Lars, additional, Sandvall, Teresa, additional, Sanjiv, Kumar, additional, Scobie, Martin, additional, Platzack, Björn, additional, Barancewski, Pawel, additional, Breuer, Olof, additional, Gorgoulis, Vassilis, additional, Pateras, Ioannis S., additional, Klockare, Maria, additional, Smith, Austin, additional, Berglund, Ulrika Warpman, additional, and Helleday, Thomas, additional

Published
2023
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27. Supplementary file 4 from Extracellular Galectin 4 Drives Immune Evasion and Promotes T-cell Apoptosis in Pancreatic Cancer

Author

Lidström, Tommy, primary, Cumming, Joshua, primary, Gaur, Rahul, primary, Frängsmyr, Lars, primary, Pateras, Ioannis S., primary, Mickert, Matthias J., primary, Franklin, Oskar, primary, Forsell, Mattias N.E., primary, Arnberg, Niklas, primary, Dongre, Mitesh, primary, Patthey, Cedric, primary, and Öhlund, Daniel, primary

Published
2023
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28. Supplementary file 5 from Extracellular Galectin 4 Drives Immune Evasion and Promotes T-cell Apoptosis in Pancreatic Cancer

Author

Lidström, Tommy, primary, Cumming, Joshua, primary, Gaur, Rahul, primary, Frängsmyr, Lars, primary, Pateras, Ioannis S., primary, Mickert, Matthias J., primary, Franklin, Oskar, primary, Forsell, Mattias N.E., primary, Arnberg, Niklas, primary, Dongre, Mitesh, primary, Patthey, Cedric, primary, and Öhlund, Daniel, primary

Published
2023
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29. Supplementary file 3 from Extracellular Galectin 4 Drives Immune Evasion and Promotes T-cell Apoptosis in Pancreatic Cancer

Author

Lidström, Tommy, primary, Cumming, Joshua, primary, Gaur, Rahul, primary, Frängsmyr, Lars, primary, Pateras, Ioannis S., primary, Mickert, Matthias J., primary, Franklin, Oskar, primary, Forsell, Mattias N.E., primary, Arnberg, Niklas, primary, Dongre, Mitesh, primary, Patthey, Cedric, primary, and Öhlund, Daniel, primary

Published
2023
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30. Supplementary Figure Legends from Extracellular Galectin 4 Drives Immune Evasion and Promotes T-cell Apoptosis in Pancreatic Cancer

Author

Lidström, Tommy, primary, Cumming, Joshua, primary, Gaur, Rahul, primary, Frängsmyr, Lars, primary, Pateras, Ioannis S., primary, Mickert, Matthias J., primary, Franklin, Oskar, primary, Forsell, Mattias N.E., primary, Arnberg, Niklas, primary, Dongre, Mitesh, primary, Patthey, Cedric, primary, and Öhlund, Daniel, primary

Published
2023
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31. Supplementary file 2 from Extracellular Galectin 4 Drives Immune Evasion and Promotes T-cell Apoptosis in Pancreatic Cancer

Author

Lidström, Tommy, primary, Cumming, Joshua, primary, Gaur, Rahul, primary, Frängsmyr, Lars, primary, Pateras, Ioannis S., primary, Mickert, Matthias J., primary, Franklin, Oskar, primary, Forsell, Mattias N.E., primary, Arnberg, Niklas, primary, Dongre, Mitesh, primary, Patthey, Cedric, primary, and Öhlund, Daniel, primary

Published
2023
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32. Supplementary Tables from Extracellular Galectin 4 Drives Immune Evasion and Promotes T-cell Apoptosis in Pancreatic Cancer

Author

Lidström, Tommy, primary, Cumming, Joshua, primary, Gaur, Rahul, primary, Frängsmyr, Lars, primary, Pateras, Ioannis S., primary, Mickert, Matthias J., primary, Franklin, Oskar, primary, Forsell, Mattias N.E., primary, Arnberg, Niklas, primary, Dongre, Mitesh, primary, Patthey, Cedric, primary, and Öhlund, Daniel, primary

Published
2023
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33. Supplementary file 1 from Extracellular Galectin 4 Drives Immune Evasion and Promotes T-cell Apoptosis in Pancreatic Cancer

Author

Lidström, Tommy, primary, Cumming, Joshua, primary, Gaur, Rahul, primary, Frängsmyr, Lars, primary, Pateras, Ioannis S., primary, Mickert, Matthias J., primary, Franklin, Oskar, primary, Forsell, Mattias N.E., primary, Arnberg, Niklas, primary, Dongre, Mitesh, primary, Patthey, Cedric, primary, and Öhlund, Daniel, primary

Published
2023
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34. Supplementary Figures 1-5 from Extracellular Galectin 4 Drives Immune Evasion and Promotes T-cell Apoptosis in Pancreatic Cancer

Author

Lidström, Tommy, primary, Cumming, Joshua, primary, Gaur, Rahul, primary, Frängsmyr, Lars, primary, Pateras, Ioannis S., primary, Mickert, Matthias J., primary, Franklin, Oskar, primary, Forsell, Mattias N.E., primary, Arnberg, Niklas, primary, Dongre, Mitesh, primary, Patthey, Cedric, primary, and Öhlund, Daniel, primary

Published
2023
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35. Supplementary data from Localized Synchrotron Irradiation of Mouse Skin Induces Persistent Systemic Genotoxic and Immune Responses

Author

Ventura, Jessica, primary, Lobachevsky, Pavel N., primary, Palazzolo, Jason S., primary, Forrester, Helen, primary, Haynes, Nicole M., primary, Ivashkevich, Alesia, primary, Stevenson, Andrew W., primary, Hall, Christopher J., primary, Ntargaras, Andreas, primary, Kotsaris, Vasilis, primary, Pollakis, Gerasimos Ch., primary, Potsi, Gianna, primary, Skordylis, Konstantinos, primary, Terzoudi, Georgia, primary, Pateras, Ioannis S., primary, Gorgoulis, Vassilis G., primary, Georgakilas, Alexandros G., primary, Sprung, Carl N., primary, and Martin, Olga A., primary

Published
2023
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36. Data from A Single-Nucleotide Substitution Mutator Phenotype Revealed by Exome Sequencing of Human Colon Adenomas

Author

Nikolaev, Sergey I., primary, Sotiriou, Sotirios K., primary, Pateras, Ioannis S., primary, Santoni, Federico, primary, Sougioultzis, Stavros, primary, Edgren, Henrik, primary, Almusa, Henrikki, primary, Robyr, Daniel, primary, Guipponi, Michel, primary, Saarela, Janna, primary, Gorgoulis, Vassilis G., primary, Antonarakis, Stylianos E., primary, and Halazonetis, Thanos D., primary

Published
2023
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37. Supplementary Figures 1-5, Tables 1-5 from A Single-Nucleotide Substitution Mutator Phenotype Revealed by Exome Sequencing of Human Colon Adenomas

Author

Nikolaev, Sergey I., primary, Sotiriou, Sotirios K., primary, Pateras, Ioannis S., primary, Santoni, Federico, primary, Sougioultzis, Stavros, primary, Edgren, Henrik, primary, Almusa, Henrikki, primary, Robyr, Daniel, primary, Guipponi, Michel, primary, Saarela, Janna, primary, Gorgoulis, Vassilis G., primary, Antonarakis, Stylianos E., primary, and Halazonetis, Thanos D., primary

Published
2023
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38. Supplementary Figure Legends 1-5 from A Single-Nucleotide Substitution Mutator Phenotype Revealed by Exome Sequencing of Human Colon Adenomas

Author

Nikolaev, Sergey I., primary, Sotiriou, Sotirios K., primary, Pateras, Ioannis S., primary, Santoni, Federico, primary, Sougioultzis, Stavros, primary, Edgren, Henrik, primary, Almusa, Henrikki, primary, Robyr, Daniel, primary, Guipponi, Michel, primary, Saarela, Janna, primary, Gorgoulis, Vassilis G., primary, Antonarakis, Stylianos E., primary, and Halazonetis, Thanos D., primary

Published
2023
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39. Genotoxin-producing Salmonella enterica induces tissue-specific types of DNA damage and DNA damage response outcomes

Author

Lopez Chiloeches, Maria, Bergonzini, Anna, Martin, Océane C. B., Bergstein, Nicole, Erttmann, Saskia F., Aung, Kyaw Min, Gekara, Nelson O., Avila Cariño, Javier, Pateras, Ioannis S., Frisan, Teresa, Lopez Chiloeches, Maria, Bergonzini, Anna, Martin, Océane C. B., Bergstein, Nicole, Erttmann, Saskia F., Aung, Kyaw Min, Gekara, Nelson O., Avila Cariño, Javier, Pateras, Ioannis S., and Frisan, Teresa

Abstract

Introduction: Typhoid toxin-expressing Salmonella enterica causes DNA damage in the intestinal mucosa in vivo, activating the DNA damage response (DDR) in the absence of inflammation. To understand whether the tissue microenvironment constrains the infection outcome, we compared the immune response and DDR patterns in the colon and liver of mice infected with a genotoxigenic strain or its isogenic control strain. Methods: In situ spatial transcriptomic and immunofluorescence have been used to assess DNA damage makers, activation of the DDR, innate immunity markers in a multiparametric analysis. Result: The presence of the typhoid toxin protected from colonic bacteria-induced inflammation, despite nuclear localization of p53, enhanced co-expression of type-I interferons (IfnbI) and the inflammasome sensor Aim2, both classic features of DNA-break-induced DDR activation. These effects were not observed in the livers of either infected group. Instead, in this tissue, the inflammatory response and DDR were associated with high oxidative stress-induced DNA damage. Conclusions: Our work highlights the relevance of the tissue microenvironment in enabling the typhoid toxin to suppress the host inflammatory response in vivo.

Published
2023
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40. Extracellular galectin 4 drives immune evasion and promotes T-cell apoptosis in pancreatic cancer

Author

Lidström, Tommy, Cumming, Joshua, Gaur, Rahul, Frängsmyr, Lars, Pateras, Ioannis S., Mickert, Matthias J., Franklin, Oskar, Forsell, Mattias N. E., Arnberg, Niklas, Dongre, Mitesh, Patthey, Cedric, Öhlund, Daniel, Lidström, Tommy, Cumming, Joshua, Gaur, Rahul, Frängsmyr, Lars, Pateras, Ioannis S., Mickert, Matthias J., Franklin, Oskar, Forsell, Mattias N. E., Arnberg, Niklas, Dongre, Mitesh, Patthey, Cedric, and Öhlund, Daniel

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by rich deposits of extracellular matrix (ECM), affecting the pathophysiology of the disease. Here, we identified galectin 4 (gal 4) as a cancer cell produced protein deposited into the ECM of PDAC tumors and detected high circulating levels of gal 4 in PDAC patients. In orthotopic transplantation experiments we observed increased infiltration of T-cells and prolonged survival in immunocompetent mice transplanted with cancer cells with reduced expression of gal 4. Increased survival was not observed in immunodeficient RAG1-/- mice, demonstrating that the effect was mediated by the adaptive immune system. Furthermore, by performing single-cell RNA-sequencing we found that the myeloid compartment and cancer-associated fibroblast (CAF) subtypes were altered in the transplanted tumors. Reduced gal 4 expression was associated with higher proportion of myofibroblastic CAFs and reduced numbers of inflammatory CAFs. We also found higher proportions of M1 macrophages, T-cells and antigen presenting dendritic cells in tumors with reduced gal 4 expression. Using a co-culture system, we observed that extracellular gal 4 induced apoptosis in T-cells by binding N-glycosylation residues on CD3 epsilon/delta. Hence, we show that gal 4 is involved in immune evasion and identify gal 4 as a promising drug target for overcoming immunosuppression in PDAC., Originally included in thesis in manuscript form.

Published
2023
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41. A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence

Author

Komseli, Eirini-Stavroula, Pateras, Ioannis S., Krejsgaard, Thorbjørn, Stawiski, Konrad, Rizou, Sophia V., Polyzos, Alexander, Roumelioti, Fani-Marlen, Chiourea, Maria, Mourkioti, Ioanna, Paparouna, Eleni, Zampetidis, Christos P., Gumeni, Sentiljana, Trougakos, Ioannis P., Pefani, Dafni-Eleftheria, O’Neill, Eric, Gagos, Sarantis, Eliopoulos, Aristides G., Fendler, Wojciech, Chowdhury, Dipanjan, Bartek, Jiri, and Gorgoulis, Vassilis G.

Published
2018
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42. Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability

Author

Galanos, Panagiotis, Pappas, George, Polyzos, Alexander, Kotsinas, Athanassios, Svolaki, Ioanna, Giakoumakis, Nickolaos N., Glytsou, Christina, Pateras, Ioannis S., Swain, Umakanta, Souliotis, Vassilis L., Georgakilas, Alexandros G., Geacintov, Nicholas, Scorrano, Luca, Lukas, Claudia, Lukas, Jiri, Livneh, Zvi, Lygerou, Zoi, Chowdhury, Dipanjan, Sørensen, Claus Storgaard, Bartek, Jiri, and Gorgoulis, Vassilis G.

Published
2018
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43. Extracellular Galectin 4 Drives Immune Evasion and Promotes T-cell Apoptosis in Pancreatic Cancer

Author

Lidström, Tommy, primary, Cumming, Joshua, additional, Gaur, Rahul, additional, Frängsmyr, Lars, additional, Pateras, Ioannis S., additional, Mickert, Matthias J., additional, Franklin, Oskar, additional, Forsell, Mattias N.E., additional, Arnberg, Niklas, additional, Dongre, Mitesh, additional, Patthey, Cedric, additional, and Öhlund, Daniel, additional

Published
2022
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44. Additional file 5 of Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming

Author

Pateras, Ioannis S., Williams, Chloe, Gianniou, Despoina D., Margetis, Aggelos T., Avgeris, Margaritis, Rousakis, Pantelis, Legaki, Aigli-Ioanna, Mirtschink, Peter, Zhang, Wei, Panoutsopoulou, Konstantina, Delis, Anastasios D., Pagakis, Stamatis N., Tang, Wei, Ambs, Stefan, Warpman Berglund, Ulrika, Helleday, Thomas, Varvarigou, Anastasia, Chatzigeorgiou, Antonios, Nordström, Anders, Tsitsilonis, Ourania E., Trougakos, Ioannis P., Gilthorpe, Jonathan D., and Frisan, Teresa

Abstract

Additional file 5: Fig. S5. ATP5A1 silencing mimicks the effect of combined STS+DXR treatment in TNBC cells - FOXO1 silencing eliminate the selective sensitivity of TNBC cells to STS+DXR treatment. a. Transcriptional levels of ATP5A1 upon ATP5A1 silencing in MCF10A and MDA-MB-231. Data are presented as mean expression values. *P ≤ 0.05. b. Transcriptional levels of FOXO1 upon FOXO1 silencing in MCF10A and MDA-MB-231. Data are presented as mean expression values. *P ≤ 0.05. c. γH2AΧ immunofluorescence staining foci per cell in MCF-10A and MDA-MB-231 cells with or without ATP5A1 silencing. Nuclei counterstained with DAPI. Scale bar, 5μm. Data are presented as mean of the number of foci per cell. *P ≤ 0.05. d. γH2AΧ immunofluorescence staining foci per cell in STS+DXR treated MCF-10A and MDA-MB-231 cells with or without FOXO1 silencing. Nuclei counterstained with DAPI. Scale bar, 5μm. Data are presented as mean of the number of foci per cell. *P ≤ 0.05. e. Transcriptional analysis of NRF2 coupled with the downstream targets NQO1 and TXNRD1 in MCF-10A and MDA-MB-231 cell lines with or without ATP5A1 silencing. Data are presented as mean expression values. *P ≤ 0.05. f. Transcriptional analysis of NRF2 coupled with the downstream targets NQO1 and TXNRD1 in STS+DXR treated MCF-10A and MDA-MB-231 cell lines with or without FOXO1 silencing. Data are presented as mean expression values. *P ≤ 0.05.

Published
2023
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45. Additional file 7 of Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming

Author

Pateras, Ioannis S., Williams, Chloe, Gianniou, Despoina D., Margetis, Aggelos T., Avgeris, Margaritis, Rousakis, Pantelis, Legaki, Aigli-Ioanna, Mirtschink, Peter, Zhang, Wei, Panoutsopoulou, Konstantina, Delis, Anastasios D., Pagakis, Stamatis N., Tang, Wei, Ambs, Stefan, Warpman Berglund, Ulrika, Helleday, Thomas, Varvarigou, Anastasia, Chatzigeorgiou, Antonios, Nordström, Anders, Tsitsilonis, Ourania E., Trougakos, Ioannis P., Gilthorpe, Jonathan D., and Frisan, Teresa

Abstract

Additional file 7: Table. S1. Weight (in grams) monitoring in control, caloric restricted (CR), DXR treated and CR+DXR treated mice.

Published
2023
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46. Additional file 4 of Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming

Author

Pateras, Ioannis S., Williams, Chloe, Gianniou, Despoina D., Margetis, Aggelos T., Avgeris, Margaritis, Rousakis, Pantelis, Legaki, Aigli-Ioanna, Mirtschink, Peter, Zhang, Wei, Panoutsopoulou, Konstantina, Delis, Anastasios D., Pagakis, Stamatis N., Tang, Wei, Ambs, Stefan, Warpman Berglund, Ulrika, Helleday, Thomas, Varvarigou, Anastasia, Chatzigeorgiou, Antonios, Nordström, Anders, Tsitsilonis, Ourania E., Trougakos, Ioannis P., Gilthorpe, Jonathan D., and Frisan, Teresa

Abstract

Additional file 4: Fig. S4. Combined treatment induces differential metabolic reprogramming. a. Intracellular metabolites profile in MCF-10A and MDA-MB-231 treated with DXR or STS+DXR. Cells were harvested on day 0, day 1 and day 2. *P ≤ 0.05. b. Expression of ATP5A in triple negative cell lines MDA-MB-468 and HS578 upon DXR or STS+DXR assessed by immunofluorescence analysis. Left panel: representative micrograph where ATP5A is shown in green, nuclei were counterstained with DAPI (blue). Scale bar, 20 μm. Right panel: Quantification, where data are presented as mean corrected total cell fluorescence (CTCF) ±SD. *P ≤ 0.05. c. Expression of ATP5A in MCF-7 and SKBR-3 cell lines upon DXR or STS+DXR assessed by immunofluorescence analysis. Left panel: representative micrograph where ATP5A is shown in green, nuclei were counterstained with DAPI (blue). Scale bar, 20 μm. Right panel: Quantification, where data are presented as mean corrected total cell fluorescence (CTCF) ±SD. *P ≤ 0.05. #Statistical trend.

Published
2023
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47. Additional file 3 of Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming

Author

Pateras, Ioannis S., Williams, Chloe, Gianniou, Despoina D., Margetis, Aggelos T., Avgeris, Margaritis, Rousakis, Pantelis, Legaki, Aigli-Ioanna, Mirtschink, Peter, Zhang, Wei, Panoutsopoulou, Konstantina, Delis, Anastasios D., Pagakis, Stamatis N., Tang, Wei, Ambs, Stefan, Warpman Berglund, Ulrika, Helleday, Thomas, Varvarigou, Anastasia, Chatzigeorgiou, Antonios, Nordström, Anders, Tsitsilonis, Ourania E., Trougakos, Ioannis P., Gilthorpe, Jonathan D., and Frisan, Teresa

Abstract

Additional file 3: Fig. S3. Combined treatment decreases oxidative phosphorylation and increases glycolytic reserve in highly aggressive TNBC cells. a. Oxygen Consumption Rate (OCR) measurements in MCF-10A and MDA-MB-231 cells treated with DXR alone or in combination with STS, using Seahorse Analyzer. Combination treatment selectively reduces basal respiration (corresponding to basal OCR), maximal respiration (corresponding to FCCP response) and spare respiratory capacity (the difference between maximal respiration and basal respiration). b. Extracellular Acidification Rate (ECAR) measurements in MCF-10A and MDA-MB-231 cells treated with DXR alone or in combination with STS, using Seahorse Analyzer. Combination treatment selectively increases glycolytic capacity, glycolytic reserve and non-glycolytic acidification in breast cancer cells. Data are presented as mean ECAR ±SD. Ns: non-significant; *P ≤ 0.05.

Published
2023
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48. Additional file 6 of Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming

Author

Pateras, Ioannis S., Williams, Chloe, Gianniou, Despoina D., Margetis, Aggelos T., Avgeris, Margaritis, Rousakis, Pantelis, Legaki, Aigli-Ioanna, Mirtschink, Peter, Zhang, Wei, Panoutsopoulou, Konstantina, Delis, Anastasios D., Pagakis, Stamatis N., Tang, Wei, Ambs, Stefan, Warpman Berglund, Ulrika, Helleday, Thomas, Varvarigou, Anastasia, Chatzigeorgiou, Antonios, Nordström, Anders, Tsitsilonis, Ourania E., Trougakos, Ioannis P., Gilthorpe, Jonathan D., and Frisan, Teresa

Abstract

Additional file 6: Fig. S6. Caloric restriction combined with chemotherapy retards tumor growth and suppresses metastatic potential in a triple-negative breast cancer mouse model. a. MTT survival assays of 4T1 mouse breast cancer cells treated with DXR alone or in combination with STS (STS+DXR). Data are presented as mean survival percentage. *P ≤ 0.05. b. Assessment of intracellular ROS production. Data are presented as mean of the fold change ±SD of intracellular ROS production in cells upon STS, DXR or combined STS+DXR. *P ≤ 0.05. c. Levels of key biochemical markers measured in serum of mice injected with 4T1 cells and treated with CR, DXR or combined CR+DXR treatment. Markers were measured in three mice from each treatment group. Data are presented as mean ±SD. One Way Anova-Kruskal Wallis test. d. Primary whole-tumor pathological specimen collected from control mice and mice treated with CR+/-DXR and euthanized at day 35. e. Mitochondria from tumor derived from control mice and mice treated with CR+/-DXR were isolated and evaluated with oxygraphy for respiration parameters. Data are presented as mean ±SD. #P

Published
2023
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49. Additional file 1 of Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming

Author

Pateras, Ioannis S., Williams, Chloe, Gianniou, Despoina D., Margetis, Aggelos T., Avgeris, Margaritis, Rousakis, Pantelis, Legaki, Aigli-Ioanna, Mirtschink, Peter, Zhang, Wei, Panoutsopoulou, Konstantina, Delis, Anastasios D., Pagakis, Stamatis N., Tang, Wei, Ambs, Stefan, Warpman Berglund, Ulrika, Helleday, Thomas, Varvarigou, Anastasia, Chatzigeorgiou, Antonios, Nordström, Anders, Tsitsilonis, Ourania E., Trougakos, Ioannis P., Gilthorpe, Jonathan D., and Frisan, Teresa

Abstract

Additional file 1: Fig. S1. Starvation preferentially sensitizes different breast cancer subtypes versus near normal cells to chemotherapy. a. In vitro treatment overview: cells were glucose/serum starved (STS) for 48 h (blue bar), drugs were added during the last 24h (red bar). b. MTT survival assays after 48 h treatment with STS with or without addition of doxorubicin (DXR) in near normal MCF-10A cells and the indicated breast cancer cell lines. Data are presented as mean survival percentage. *P ≤ 0.05. c. MTT survival assay after 48 h treatment with STS with or without 100 nM doxorubicin (DXR) in near normal MCF10A cells and the triple negative breast cancer cells MDA-MB-231, MDA-MB-468 and HS578. Data are presented as mean survival percentage. *P ≤ 0.05. d. MTT survival assays after 48 h treatment with STS with or without addition of cisplatin (CIS) in near normal MCF-10A cells and the indicated breast cancer cell lines. Data are presented as mean survival percentage. *P ≤ 0.05.

Published
2023
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50. Additional file 2 of Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming

Author

Pateras, Ioannis S., Williams, Chloe, Gianniou, Despoina D., Margetis, Aggelos T., Avgeris, Margaritis, Rousakis, Pantelis, Legaki, Aigli-Ioanna, Mirtschink, Peter, Zhang, Wei, Panoutsopoulou, Konstantina, Delis, Anastasios D., Pagakis, Stamatis N., Tang, Wei, Ambs, Stefan, Warpman Berglund, Ulrika, Helleday, Thomas, Varvarigou, Anastasia, Chatzigeorgiou, Antonios, Nordström, Anders, Tsitsilonis, Ourania E., Trougakos, Ioannis P., Gilthorpe, Jonathan D., and Frisan, Teresa

Abstract

Additional file 2: Fig. S2. Differential accumulation of reactive oxygen species in malignant and near normal epithelial breast cells after starvation. a. Assessment of intracellular ROS production; fold change of intracellular ROS production compared to control in breast cancer cell lines upon STS, DXR or combined treatment (STS+DXR). Data are presented as mean fluorescent intensity +SD. *P ≤ 0.05. b. MTT survival assay after 48 h treatment with combined STS+DXR in absence or presence of NAC (4mM) in MDA-MB-231 cells. Data are presented as mean survival percentage. *P ≤ 0.05. c. Transcriptional analysis of NRF2 coupled with the downstream transcriptional targets NQO1 and TXNRD1 in the presented conditions in MCF-10A, MDA-MB-231, MDA-MB-468 and HS578 cell lines. Data are presented as mean expression values. *P ≤ 0.05. d. MTT survival assays after 48 h treatment with STS with or without addition of ΤΗ1579 in near normal MCF-10A cells and the indicated breast cancer cell lines. Data are presented as mean survival percentage. *P ≤ 0.05. e. γH2AΧ immunofluorescence staining in MCF-10A, MDA-MB-231, MDA-MB-468 and HS578 in Control (CTRL), DXR, STS and STS+DXR. Nuclei counterstained with DAPI. Scale bar, 5μm. Data are presented as mean of the number of foci per cell. *P ≤ 0.05.

Published
2023
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