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2. Gliosarcoma associated with bilateral hippocampal sclerosis in a cat presenting complex partial seizures with orofacial involvement: A case report.

Author

Martinez, Ana, Binks, Sophie, Pumarola, Martí, Hardas, Alexandros, Easton, Alistair, Campo, Leticia, Browne, Molly, Martins, Susana, Garosi, Laurent S., Di Dona, Francesco, and Tauro, Anna

Subjects
HIPPOCAMPAL sclerosis, POTASSIUM channels, INTRACRANIAL tumors, CATS, IMMUNOHISTOCHEMISTRY
Abstract

Key Clinical Message: Gliosarcoma, a rare cerebral neoplasm, has not been linked to hippocampal changes in cats. We report a case of complex partial seizures with orofacial involvement, revealing gliosarcoma concurrent with bilateral hippocampal sclerosis. A 16‐year‐old neutered female domestic shorthair cat presented with acute inappetence, ataxia, disorientation, and vacant staring. Brain MRI revealed an ill‐defined, round, intra‐axial mass in the right piriform lobe, showing hyperintensity on T2W, T2‐FLAIR, and T2*W, and hypointensity on T1W images. The lesion exhibited mass effect and contrast enhancement in its center. Bilateral hyperintensity on T2‐FLAIR images and contrast enhancement were observed in the hippocampus. Brain histologic and immunohistochemical analysis revealed cerebral gliosarcoma with concurrent hippocampal sclerosis. Feline LGI1‐antibody testing on the serum and/or CSF was not performed due to insufficient biomaterial. Although retrospective testing on brain tissue was considered, it ultimately proved unfeasible, preventing us from ruling out antibody‐associated limbic encephalitis. In conclusion, cerebral gliosarcoma should be included in feline intracranial tumor differentials, warranting brain MRI and feline LGI1‐antibody testing in cats showing complex partial seizures with orofacial involvement. In our case, the prognosis remained poor due to the presence of a high‐grade glioma. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Morphometric Analysis of the Thymic Epithelial Cell (TEC) Network Using Integrated and Orthogonal Digital Pathology Approaches

Author

Lagou, Maria K., primary, Argyris, Dimitrios G., additional, Vodopyanov, Stepan, additional, Gunther-Cummins, Leslie, additional, Hardas, Alexandros, additional, Poutahidis, Theofilos, additional, Panorias, Christos, additional, DesMarais, Sophia, additional, Entenberg, Conner, additional, Carpenter, Randall S., additional, Guzik, Hillary, additional, Nishku, Xheni, additional, Churaman, Joseph, additional, Maryanovich, Maria, additional, DesMarais, Vera, additional, Macaluso, Frank P., additional, and Karagiannis, George S., additional

Published
2024
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4. Cancer Associated Bacteria in Primary and Metastatic Non-Small Cell Lung Cancer

Author

Thakkar, Krupa, primary, Richard, Corentin, additional, Fu, Hongchang, additional, Simpson, Benjamin S., additional, Cha, Hongui, additional, Augustine, Marcellus, additional, Coulton, Alexander, additional, Castro, Andrea, additional, Veerian, Selvaraju, additional, AbdulJabbar, Khalid, additional, Zhang, Hanyun, additional, Hardas, Alexandros, additional, Al-Sawaf, Othman, additional, Huebner, Arianna, additional, Al-Bakir, Maise, additional, Karasaki, Takahiro, additional, Pich, Oriol, additional, Bailey, Chris, additional, Seo, Yongwoo David, additional, Damania, Ashish, additional, Chelvanambi, Manoj, additional, Ajami, Nadim J., additional, Moore, David, additional, Sivakumar, Monika, additional, Hill, Mark, additional, Frankell, Alexander, additional, Ward, Sophie, additional, Naceur-Lombardelli, Cristina, additional, Salgado, Roberto, additional, Akarca, Ayse, additional, Marafioti, Teresa, additional, McGranahan, Nicholas, additional, Jamal-Hanjani, Mariam, additional, Wargo, Jennifer, additional, Santini, Joanne, additional, Swanton, Charles, additional, and Litchfield, Kevin, additional

Published
2024
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5. Emergence and spread of feline infection peritonitis due to a highly pathogenic canine/feline recombinant coronavirus

Author

Tait-Burkard, Christine, primary, Atippa, Charalampos, additional, Warr, Amanda, additional, Epaminondas, Demetris, additional, O'Shea, Marie, additional, Fletcher, Sarah, additional, Malbon, Alexandra, additional, Lyraki, Maria, additional, Hammond, Rachael, additional, Hardas, Alexandros, additional, Zanti, Antria, additional, Loukaidou, Stavroula, additional, Gentil, Michaela, additional, Gunn-Moore, Danielle, additional, and Mazeri, Stella, additional

Published
2023
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6. Emergence and spread of feline infection peritonitis due to a highly pathogenic canine/feline recombinant coronavirus

Author

Atippa, Charalampos, primary, Warr, Amanda Susan, additional, Epaminondas, Demetris, additional, O'Shea, Marie, additional, Fletcher, Sarah Louise, additional, Malbon, Alexandra, additional, Lyraki, Maria, additional, Hammond, Rachael, additional, Hardas, Alexandros, additional, Zanti, Antria, additional, Loukaidou, Stavroula, additional, Gentil, Michaela, additional, Gunn-Moore, Danielle, additional, Mazeri, Stella, additional, and Tait-Burkard, Christine, additional

Published
2023
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7. Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning

Author

Meehan, Gavin R., primary, Herder, Vanessa, additional, Allan, Jay, additional, Huang, Xinyi, additional, Kerr, Karen, additional, Mendonca, Diogo Correa, additional, Ilia, Georgios, additional, Wright, Derek W., additional, Nomikou, Kyriaki, additional, Gu, Quan, additional, Molina Arias, Sergi, additional, Hansmann, Florian, additional, Hardas, Alexandros, additional, Attipa, Charalampos, additional, De Lorenzo, Giuditta, additional, Cowton, Vanessa, additional, Upfold, Nicole, additional, Palmalux, Natasha, additional, Brown, Jonathan C., additional, Barclay, Wendy S., additional, Filipe, Ana Da Silva, additional, Furnon, Wilhelm, additional, Patel, Arvind H., additional, and Palmarini, Massimo, additional

Published
2023
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8. Spatial analyses of immune cell infiltration in cancer: current methods and future directions. A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer

Author

Page, David B, primary, Broeckx, Glenn, additional, Jahangir, Chowdhury Arif, additional, Verbandt, Sara, additional, Gupta, Rajarsi R, additional, Thagaard, Jeppe, additional, Khiroya, Reena, additional, Kos, Zuzana, additional, Abduljabbar, Khalid, additional, Acosta Haab, Gabriela, additional, Acs, Balazs, additional, Almeida, Jonas S, additional, Alvarado‐Cabrero, Isabel, additional, Azmoudeh‐Ardalan, Farid, additional, Badve, Sunil, additional, Baharun, Nurkhairul Bariyah, additional, Bellolio, Enrique R, additional, Bheemaraju, Vydehi, additional, Blenman, Kim RM, additional, Botinelly Mendonça Fujimoto, Luciana, additional, Burgues, Octavio, additional, Cheang, Maggie Chon U, additional, Ciompi, Francesco, additional, Cooper, Lee AD, additional, Coosemans, An, additional, Corredor, Germán, additional, Dantas Portela, Flavio Luis, additional, Deman, Frederik, additional, Demaria, Sandra, additional, Dudgeon, Sarah N, additional, Elghazawy, Mahmoud, additional, Ely, Scott, additional, Fernandez‐Martín, Claudio, additional, Fineberg, Susan, additional, Fox, Stephen B, additional, Gallagher, William M, additional, Giltnane, Jennifer M, additional, Gnjatic, Sacha, additional, Gonzalez‐Ericsson, Paula I, additional, Grigoriadis, Anita, additional, Halama, Niels, additional, Hanna, Matthew G, additional, Harbhajanka, Aparna, additional, Hardas, Alexandros, additional, Hart, Steven N, additional, Hartman, Johan, additional, Hewitt, Stephen, additional, Hida, Akira I, additional, Horlings, Hugo M, additional, Husain, Zaheed, additional, Hytopoulos, Evangelos, additional, Irshad, Sheeba, additional, Janssen, Emiel AM, additional, Kahila, Mohamed, additional, Kataoka, Tatsuki R, additional, Kawaguchi, Kosuke, additional, Kharidehal, Durga, additional, Khramtsov, Andrey I, additional, Kiraz, Umay, additional, Kirtani, Pawan, additional, Kodach, Liudmila L, additional, Korski, Konstanty, additional, Kovács, Anikó, additional, Laenkholm, Anne‐Vibeke, additional, Lang‐Schwarz, Corinna, additional, Larsimont, Denis, additional, Lennerz, Jochen K, additional, Lerousseau, Marvin, additional, Li, Xiaoxian, additional, Ly, Amy, additional, Madabhushi, Anant, additional, Maley, Sai K, additional, Manur Narasimhamurthy, Vidya, additional, Marks, Douglas K, additional, McDonald, Elizabeth S, additional, Mehrotra, Ravi, additional, Michiels, Stefan, additional, Minhas, Fayyaz ul Amir Afsar, additional, Mittal, Shachi, additional, Moore, David A, additional, Mushtaq, Shamim, additional, Nighat, Hussain, additional, Papathomas, Thomas, additional, Penault‐Llorca, Frederique, additional, Perera, Rashindrie D, additional, Pinard, Christopher J, additional, Pinto‐Cardenas, Juan Carlos, additional, Pruneri, Giancarlo, additional, Pusztai, Lajos, additional, Rahman, Arman, additional, Rajpoot, Nasir Mahmood, additional, Rapoport, Bernardo Leon, additional, Rau, Tilman T, additional, Reis‐Filho, Jorge S, additional, Ribeiro, Joana M, additional, Rimm, David, additional, Salomon, Anne‐Vincent, additional, Salto‐Tellez, Manuel, additional, Saltz, Joel, additional, Sayed, Shahin, additional, Siziopikou, Kalliopi P, additional, Sotiriou, Christos, additional, Stenzinger, Albrecht, additional, Sughayer, Maher A, additional, Sur, Daniel, additional, Symmans, Fraser, additional, Tanaka, Sunao, additional, Taxter, Timothy, additional, Tejpar, Sabine, additional, Teuwen, Jonas, additional, Thompson, E Aubrey, additional, Tramm, Trine, additional, Tran, William T, additional, van der Laak, Jeroen, additional, van Diest, Paul J, additional, Verghese, Gregory E, additional, Viale, Giuseppe, additional, Vieth, Michael, additional, Wahab, Noorul, additional, Walter, Thomas, additional, Waumans, Yannick, additional, Wen, Hannah Y, additional, Yang, Wentao, additional, Yuan, Yinyin, additional, Adams, Sylvia, additional, Bartlett, John Mark Seaverns, additional, Loibl, Sibylle, additional, Denkert, Carsten, additional, Savas, Peter, additional, Loi, Sherene, additional, Salgado, Roberto, additional, Specht Stovgaard, Elisabeth, additional, Akturk, Guray, additional, and Bouchmaa, Najat, additional

Published
2023
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10. Microbial lysate upregulates host oxytocin

Author

Varian, Bernard J., Poutahidis, Theofilos, DiBenedictis, Brett T., Levkovich, Tatiana, Ibrahim, Yassin, Didyk, Eliska, Shikhman, Lana, Cheung, Harry K., Hardas, Alexandros, Ricciardi, Catherine E., Kolandaivelu, Kumaran, Veenema, Alexa H., Alm, Eric J., and Erdman, Susan E.

Published
2017
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12. Kinetics of endogenous thymic regeneration following chemotherapy-induced involution

Author

Lagou, Maria K, primary, Carpenter, Randall S., additional, Anastasiadou, Dimitra P., additional, Hardas, Alexandros, additional, Garcia, Raquel Vallejo, additional, Argyris, Dimitris G., additional, Chondronikola, Anastasia-Aristoteleia, additional, Licausi, Francesca, additional, Briceno, Andrea, additional, Guzik, Hillary, additional, DesMarais, Vera, additional, Branch, Craig A., additional, Cui, Min-Hui, additional, Poutahidis, Theofilos, additional, Angelopoulou, Katerina, additional, Maryanovich, Maria, additional, and Karagiannis, George S., additional

Published
2023
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14. Spatial analyses of immune cell infiltration in cancer: current methods and future directions. A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Author

Pathologie, Cancer, Page, David B, Broeckx, Glenn, Jahangir, Chowdhury Arif, Verbandt, Sara, Gupta, Rajarsi R, Thagaard, Jeppe, Khiroya, Reena, Kos, Zuzana, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Cheang, Maggie Chon U, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N, Elghazawy, Mahmoud, Ely, Scott, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hardas, Alexandros, Hart, Steven N, Hartman, Johan, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Salomon, Anne-Vincent, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Adams, Sylvia, Bartlett, John Mark Seaverns, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Akturk, Guray, Bouchmaa, Najat, Pathologie, Cancer, Page, David B, Broeckx, Glenn, Jahangir, Chowdhury Arif, Verbandt, Sara, Gupta, Rajarsi R, Thagaard, Jeppe, Khiroya, Reena, Kos, Zuzana, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Cheang, Maggie Chon U, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N, Elghazawy, Mahmoud, Ely, Scott, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hardas, Alexandros, Hart, Steven N, Hartman, Johan, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Salomon, Anne-Vincent, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Adams, Sylvia, Bartlett, John Mark Seaverns, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Akturk, Guray, and Bouchmaa, Najat

Published
2023

15. Concerning feline infectious peritonitis outbreak in Cyprus

Author

Attipa, Charalampos, Gunn-Moore, Danielle, Mazeri, Stella, Epaminondas, Demetris, Lyraki, Maria, Hardas, Alexandros, Loukaidou, Stavroula, and Gentil, Michaela

Subjects
Cats, Disease Outbreaks/veterinary, Animals, Cyprus/epidemiology, Cat Diseases/epidemiology, Feline Infectious Peritonitis
Published
2023
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16. A CADASIL NOTCH3mutation leads to clonal hematopoiesis and expansion of Dnmt3a-R878Hhematopoietic clones

Author

Sánchez-Lanzas, Raúl, Barclay, Justin, Hardas, Alexandros, Kalampalika, Foteini, Jiménez-Pompa, Amanda, Gallipoli, Paolo, and Ganuza, Miguel

Abstract

Clonal hematopoiesis (CH) is nearly universal in the elderly. The molecular and cellular mechanisms driving CH and the clinical consequences of carrying clonally derived mutant mature blood cells are poorly understood. We recently identified a C223Y mutation in the extracellular domain (ECD) of NOTCH3 as a putative CH driver in mice. Provocatively, germline NOTCH3ECD mutations perturbing cysteine numbers cause Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a type of vascular dementia, suggesting an unexpected link between CADASIL and CH. Here, we formally demonstrated that mouse hematopoietic stem and progenitor cells (HSPCs) expressing CADASIL-related NOTCH3C455Rexhibit a proliferative advantage resulting in robust cellular expansion in vivo and in vitro. Co-expression of NOTCH3C455Rand Dnmt3aR878H, homologous to a frequent human CH mutation, increased the fitness of NOTCH3C455RHSPCs, demonstrating their functional cooperation. Surprisingly, the presence of NOTCH3C455Rhematopoietic cells supported the expansion of Dnmt3aR878HHSPCs in a non-cell autonomous fashion in vivo, strongly suggesting that CADASIL patients and asymptomatic carriers can be highly predisposed to DNMT3AR882H-driven CH. Considering that CADASIL-related NOTCH3mutations are more frequent in the general population than anticipated (~1 carrier in 400 people), the effect of these NOTCH3mutations on CH development should be considered.

Published
2024
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17. Comparative Evaluation of Tumor-Infiltrating Lymphocytes in Companion Animals: Immuno-Oncology as a Relevant Translational Model for Cancer Therapy

Author

Pinard, Christopher J., primary, Lagree, Andrew, additional, Lu, Fang-I, additional, Klein, Jonathan, additional, Oblak, Michelle L., additional, Salgado, Roberto, additional, Cardenas, Juan Carlos Pinto, additional, Brunetti, Barbara, additional, Muscatello, Luisa Vera, additional, Sarli, Giuseppe, additional, Foschini, Maria Pia, additional, Hardas, Alexandros, additional, Castillo, Simon P., additional, AbdulJabbar, Khalid, additional, Yuan, Yinyin, additional, Moore, David A., additional, and Tran, William T., additional

Published
2022
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22. HDAC1/2 Inhibitor Romidepsin Suppresses DEN-Induced Hepatocellular Carcinogenesis in Mice

Author

Afaloniati, Hara, Angelopoulou, Katerina, Giakoustidis, Alexander, Hardas, Alexandros, Pseftogas, Athanasios, Makedou, Kali, Gargavanis, Athanasios, Goulopoulos, Thomas, Iliadis, Stavros, Papadopoulos, Vasileios, Papalois, Apostolos, Mosialos, George, Poutahidis, Theofilos, and Giakoustidis, Dimitrios

Subjects
DEN, HDAC inhibitors, diethylnitrosamine, HDAC, HDACi, hepatocellular carcinoma, HCC, histone deacetylases, OncoTargets and Therapy, Original Research, Romidepsin
Abstract

Hara Afaloniati,1 Katerina Angelopoulou,1 Alexander Giakoustidis,2 Alexandros Hardas,3 Athanasios Pseftogas,4 Kali Makedou,5 Athanasios Gargavanis,2 Thomas Goulopoulos,2 Stavros Iliadis,5 Vasileios Papadopoulos,2 Apostolos Papalois,6 George Mosialos,4 Theofilos Poutahidis,3 Dimitrios Giakoustidis2 1Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2First Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, Greece; 3Laboratory of Pathology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 5Department of Biological Chemistry, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 6Experimental, Educational and Research Center, ELPEN, Pikermi, Attica, GreeceCorrespondence: Dimitrios GiakoustidisFirst Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, GreeceTel +30 6932306133Email dgiak@auth.grBackground: Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes the need for early detection and aggressive intervention. Based on the knowledge that hepatocarcinogenesis is significantly influenced by histone acetylation, we directed our search for novel HCC therapeutics among histone deacetylation inhibitors (HDACi). The aim of the present study was to investigate the effect of HDAC1/2 inhibitor Romidepsin in the well-established mouse model of diethylnitrosamine (DEN)-induced HCC.Materials and Methods: C56BL/6 mice were treated with Romidepsin at the critical point of 10 months after DEN challenge and their livers were examined 2 months later using histopathology and morphometry. Protein levels were assessed in serum using ELISA and in liver tissues using Western blot and immunohistochemistry (in-situ detection). Gene expression was quantified using real-time PCR.Results: Romidepsin suppressed cancer progression. This effect was associated with decreased proliferation and increased apoptosis of cancer cells. The cell cycle regulator CK2a, the anti-inflammatory molecule PPAR-γ, and the tumor suppressors PTEN and CYLD were upregulated in treated HCC. By contrast, the expression of PI3K, NF-κB p65 and c-Jun was reduced. In line with this result, the levels of two major apoptosis regulators, ie, BAD and the multifunctional protein c-Met, were lower in the blood serum of treated mice compared to the untreated mice with HCC.Conclusion: These findings suggest that Romidepsin, a drug currently used in the treatment of lymphoma, could also be considered in the management of early-stage HCC.Keywords: diethylnitrosamine, DEN, histone deacetylases, HDAC, HDAC inhibitors, HDACi, hepatocellular carcinoma, HCC, Romidepsin

Published
2020

23. HDAC1/2 Inhibitor Romidepsin Suppresses DEN-Induced Hepatocellular Carcinogenesis in Mice

Author

Afaloniati,Hara, Angelopoulou,Katerina, Giakoustidis,Alexander, Hardas,Alexandros, Pseftogas,Athanasios, Makedou,Kali, Gargavanis,Athanasios, Goulopoulos,Thomas, Iliadis,Stavros, Papadopoulos,Vasileios, Papalois,Apostolos, Mosialos,George, Poutahidis,Theofilos, Giakoustidis,Dimitrios, Afaloniati,Hara, Angelopoulou,Katerina, Giakoustidis,Alexander, Hardas,Alexandros, Pseftogas,Athanasios, Makedou,Kali, Gargavanis,Athanasios, Goulopoulos,Thomas, Iliadis,Stavros, Papadopoulos,Vasileios, Papalois,Apostolos, Mosialos,George, Poutahidis,Theofilos, and Giakoustidis,Dimitrios

Abstract

Hara Afaloniati,1 Katerina Angelopoulou,1 Alexander Giakoustidis,2 Alexandros Hardas,3 Athanasios Pseftogas,4 Kali Makedou,5 Athanasios Gargavanis,2 Thomas Goulopoulos,2 Stavros Iliadis,5 Vasileios Papadopoulos,2 Apostolos Papalois,6 George Mosialos,4 Theofilos Poutahidis,3 Dimitrios Giakoustidis2 1Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2First Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, Greece; 3Laboratory of Pathology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 5Department of Biological Chemistry, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 6Experimental, Educational and Research Center, ELPEN, Pikermi, Attica, GreeceCorrespondence: Dimitrios GiakoustidisFirst Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, GreeceTel +30 6932306133Email dgiak@auth.grBackground: Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes the need for early detection and aggressive intervention. Based on the knowledge that hepatocarcinogenesis is significantly influenced by histone acetylation, we directed our search for novel HCC therapeutics among histone deacetylation inhibitors (HDACi). The aim of the present study was to investigate the effect of HDAC1/2 inhibitor Romidepsin in the well-established mouse model of diethylnitrosamine (DEN)-induced HCC.Materials and Methods: C56BL/6 mice were treated with Romidepsin at the critical

Published
2020

24. Microbial lysate upregulates host oxytocin

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Civil and Environmental Engineering, Massachusetts Institute of Technology. Division of Comparative Medicine, Varian, Bernard, Didyk, Eliska, Alm, Eric J, Poutahidis, Theofilos, DiBenedictis, Brett T., Levkovich, Tatiana, Ibrahim, Yassin, Shikhman, Lana, Cheung, Harry K., Hardas, Alexandros, Ricciardi, Catherine E., Kolandaivelu, Kumaran, Veenema, Alexa H., Erdman, Susan E., Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Civil and Environmental Engineering, Massachusetts Institute of Technology. Division of Comparative Medicine, Varian, Bernard, Didyk, Eliska, Alm, Eric J, Poutahidis, Theofilos, DiBenedictis, Brett T., Levkovich, Tatiana, Ibrahim, Yassin, Shikhman, Lana, Cheung, Harry K., Hardas, Alexandros, Ricciardi, Catherine E., Kolandaivelu, Kumaran, Veenema, Alexa H., and Erdman, Susan E.

Abstract

Neuropeptide hormone oxytocin has roles in social bonding, energy metabolism, and wound healing contributing to good physical, mental and social health. It was previously shown that feeding of a human commensal microbe Lactobacillus reuteri (L. reuteri) is sufficient to up-regulate endogenous oxytocin levels and improve wound healing capacity in mice. Here we show that oral L. reuteri-induced skin wound repair benefits extend to human subjects. Further, dietary supplementation with a sterile lysate of this microbe alone is sufficient to boost systemic oxytocin levels and improve wound repair capacity. Oxytocin-producing cells were found to be increased in the caudal paraventricular nucleus [PVN] of the hypothalamus after feeding of a sterile lysed preparation of L. reuteri, coincident with lowered blood levels of stress hormone corticosterone and more rapid epidermal closure, in mouse models. We conclude that microbe viability is not essential for regulating host oxytocin levels. The results suggest that a peptide or metabolite produced by bacteria may modulate host oxytocin secretion for potential public or personalized health goals. Keywords: Bacteria; Postbiotic; Stress; Corticosterone; Thymus; Wound healing

Published
2018

25. Distal partial ulnectomy with ulnar styloid process excision for management of an aneurysmal bone cyst in a cat.

Author

Sanchez Villamil C, Llanos Diez C, Thomas G, Garty R, Lappalainen M, Klever J, and Hardas A

Abstract

Case Summary: An 8-year-old male neutered domestic shorthair cat was presented with an acute onset of left thoracic limb lameness and a firm swelling on the lateral aspect of the left distal antebrachium. A CT scan of the left thoracic limb revealed an expansile osteolytic cystic bone lesion centred at the distal left ulnar metaphysis. Cytology from fine-needle aspiration was not consistent with neoplasia. The CT features and the cytology results were suggestive of a bone cyst. A distal partial ulnectomy with ulnar styloid process excision was performed as the biopsy method and as the treatment approach. Histopathology results were consistent with an aneurysmal bone cyst (ABC). Carpal instability was not detected after distal partial ulnectomy; therefore, a stabilisation method was not required. Limb function was excellent after surgery, with no lameness and no recurrence detected by the owner at 2, 6 and 24 weeks postoperatively. The veterinary examination at 12 weeks postoperatively confirmed the owner's outcome assessment., Relevance and Novel Information: To the authors' knowledge, this is the first report describing a distal partial ulnectomy with ulnar styloid process excision in a cat. Despite disrupting the short ulnar collateral ligament, this technique provided excellent short-term limb function with no need for carpal joint stabilisation. This technique allowed for the complete excision of a distal ulnar ABC and avoided cyst debridement, which could be associated with haemorrhage, recurrence and malignant transformation. Distal partial ulnectomy should be considered for distal ulnar bone lesions in cats., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Published
2024
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26. Morphometric Analysis of the Thymic Epithelial Cell (TEC) Network Using Integrated and Orthogonal Digital Pathology Approaches.

Author

Lagou MK, Argyris DG, Vodopyanov S, Gunther-Cummins L, Hardas A, Poutahidis T, Panorias C, DesMarais S, Entenberg C, Carpenter RS, Guzik H, Nishku X, Churaman J, Maryanovich M, DesMarais V, Macaluso FP, and Karagiannis GS

Abstract

The thymus, a central primary lymphoid organ of the immune system, plays a key role in T cell development. Surprisingly, the thymus is quite neglected with regards to standardized pathology approaches and practices for assessing structure and function. Most studies use multispectral flow cytometry to define the dynamic composition of the thymus at the cell population level, but they are limited by lack of contextual insight. This knowledge gap hinders our understanding of various thymic conditions and pathologies, particularly how they affect thymic architecture, and subsequently, immune competence. Here, we introduce a digital pathology pipeline to address these challenges. Our approach can be coupled to analytical algorithms and utilizes rationalized morphometric assessments of thymic tissue, ranging from tissue-wide down to microanatomical and ultrastructural levels. This pipeline enables the quantitative assessment of putative changes and adaptations of thymic structure to stimuli, offering valuable insights into the pathophysiology of thymic disorders. This versatile pipeline can be applied to a wide range of conditions that may directly or indirectly affect thymic structure, ranging from various cytotoxic stimuli inducing acute thymic involution to autoimmune diseases, such as myasthenia gravis. Here, we demonstrate applicability of the method in a mouse model of age-dependent thymic involution, both by confirming established knowledge, and by providing novel insights on intrathymic remodeling in the aged thymus. Our orthogonal pipeline, with its high versatility and depth of analysis, promises to be a valuable and practical toolset for both basic and translational immunology laboratories investigating thymic function and disease.

Published
2024
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