TY - JOUR AU - Daradics, Noémi AU - Horváth, Gergő AU - Tretter, László AU - Paál, Ágnes AU - Fülöp, András AU - Budai, András AU - Szijártó, Attila TI - The effect of Cyclophilin D depletion on liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy JF - PLOS ONE J2 - PLOS ONE VL - 17 PY - 2022 IS - 7 PG - 15 SN - 1932-6203 DO - 10.1371/journal.pone.0271606 UR - https://m2.mtmt.hu/api/publication/32989211 ID - 32989211 N1 - These authors contributed equally to this work: Andras Budai, Attila Szijarto AB - Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a modification of two-stage hepatectomy profitable for patients with inoperable hepatic tumors by standard techniques. Unfortunately, initially poor postoperative outcome was associated with ALPPS, in which mitochondrial dysfunction played an essential role. Inhibition of cyclophilins has been already proposed to be efficient as a mitochondrial therapy in liver diseases. To investigate the effect of Cyclophilin D (CypD) depletion on mitochondrial function, biogenesis and liver regeneration following ALPPS a CypD knockout (KO) mice model was created.Male wild type (WT) (n = 30) and CypD KO (n = 30) mice underwent ALPPS procedure. Animals were terminated pre-operatively and 24, 48, 72 or 168 h after the operation. Mitochondrial functional studies and proteomic analysis were performed. Regeneration rate and mitotic activity were assessed.The CypD KO group displayed improved mitochondrial function, as both ATP production (P < 0.001) and oxygen consumption (P < 0.05) were increased compared to the WT group. The level of mitochondrial biogenesis coordinator peroxisome proliferator-activated receptor γ co-activator 1-α (PGC1-α) was also elevated in the CypD KO group (P < 0.001), which resulted in the induction of the mitochondrial oxidative phosphorylation system. Liver growth increased in the CypD KO group compared to the WT group (P < 0.001).Our study demonstrates the beneficial effect of CypD depletion on the mitochondrial vulnerability following ALPPS. Based on our results we propose that CypD inhibition should be further investigated as a possible mitochondrial therapy following ALPPS. LA - English DB - MTMT ER - TY - JOUR AU - Daradics, Noémi AU - Olthof, P.B. AU - Budai, András AU - Heger, M. AU - van, Gulik T.M. AU - Fülöp, András AU - Szijártó, Attila TI - The role of farnesoid X receptor in accelerated liver regeneration in rats subjected to ALPPS JF - CURRENT ONCOLOGY (TORONTO) J2 - CURR ONCOL VL - 28 PY - 2021 IS - 6 SP - 5240 EP - 5254 PG - 15 SN - 1198-0052 DO - 10.3390/curroncol28060438 UR - https://m2.mtmt.hu/api/publication/32552854 ID - 32552854 N1 - Hepato-Pancreatico-Biliary (HPB) Surgical Research Center Hungary, Department of Surgery, Transplantation and Interventional Gastroenterology, Semmelweis University, Budapest, 1082, Hungary Erasmus Medical Center, Department of Surgery, Rotterdam, 3015 GD, Netherlands 2nd Department of Pathology, Semmelweis University, Budapest, 1091, Hungary Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, 314001, China Laboratory of Experimental Oncology, Department of Pathology, Erasmus Medical Center, Rotterdam, 3015 GD, Netherlands Department of Surgery, Academic Medical Center, Amsterdam, 1105 AZ, Netherlands Export Date: 29 December 2021 CODEN: CUONF Correspondence Address: Daradics, N.; Hepato-Pancreatico-Biliary (HPB) Surgical Research Center Hungary, Hungary; email: daradics.noemi@gmail.com LA - English DB - MTMT ER - TY - JOUR AU - Németh , Kristóf AU - Budai, András TI - Az intraduktális papilláris mucinózus neoplázia (Ipmn) jellegzetességei JF - MAGYAR ONKOLÓGIA J2 - MAGYAR ONKOLÓGIA VL - 65 PY - 2021 IS - 3 SP - 223 EP - 230 PG - 8 SN - 0025-0244 UR - https://m2.mtmt.hu/api/publication/32461928 ID - 32461928 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Fard-Aghaie, Mohammed-Hossein AU - Budai, András AU - Daradics, Noémi AU - Horváth, Gergő AU - Oldhafer, Karl AU - Szijártó, Attila AU - Fülöp, András TI - The effects of physical prehabilitation: Improved liver regeneration and mitochondrial function after ALPPS operation in a rodent model JF - JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES J2 - J HEPATO-BIL-PAN SCI VL - 28 PY - 2021 IS - 8 SP - 692 EP - 702 PG - 11 SN - 1868-6974 DO - 10.1002/jhbp.945 UR - https://m2.mtmt.hu/api/publication/32175343 ID - 32175343 N1 - Fard- Aghaie and Budai contributed equally to this article AB - Background: To identify the role of physical prehabilitation (PP) in liver regeneration, mitochondrial function, biogenesis, and inflammatory response was investigated after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in a rodent model. Methods: Male Wistar rats (n = 60) underwent ALPPS. Animals were divided (n = 30) to the physical prehabilitation group (PP) and sedentary group (S). The animals were exsanguinated before (0 hour) and 24, 48, 72, or 168 hours after the operation. Regeneration rate and proliferation index were assessed. Mitochondrial function, biogenesis, and inflammatory response were evaluated. Results: Regeneration rate and Ki67 index were significantly increased in the PP group compared to the S group (P <.001). Due to the changes in oxidative capacity and ATP production rate, the P/O ratio of PP group compared to the S group was significantly increased (P <.05). PP group was characterized by accelerated mitochondrial biogenesis and less intense inflammatory response compared to the S group. Conclusions: To our knowledge, this is the first demonstration of the beneficial effects of PP on liver regeneration, mitochondrial function, biogenesis, and the inflammatory response after ALPPS. © 2021 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery LA - English DB - MTMT ER - TY - THES AU - Budai, András TI - Morfológiai és funkcionális változások akcelerált májregeneráció során PY - 2020 DO - 10.14753/SE.2020.2368 UR - https://m2.mtmt.hu/api/publication/31866300 ID - 31866300 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Budai, András AU - Horváth, Gergő AU - Tretter, László AU - Radák, Zsolt AU - Koltai, Erika AU - Bori, Zoltán AU - Torma, Ferenc Gergely AU - Lukáts, Ákos AU - Röhlich, Pál AU - Szijártó, Attila AU - Fülöp, András TI - Mitochondrial function after associating liver partition and portal vein ligation for staged hepatectomy in an experimental model JF - BRITISH JOURNAL OF SURGERY J2 - BRIT J SURG VL - 106 PY - 2019 IS - 1 SP - 120 EP - 131 PG - 12 SN - 0007-1323 DO - 10.1002/bjs.10978 UR - https://m2.mtmt.hu/api/publication/3426954 ID - 3426954 LA - English DB - MTMT ER - TY - JOUR AU - Budai, András AU - Fülöp, András AU - Hahn, Oszkár AU - Ónody, Péter Zoltán AU - Kovács, Tibor AU - Németh, Tibor AU - Dunay, Miklós Pál AU - Szijártó, Attila TI - Animal Models for Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS): Achievements and Future Perspectives JF - EUROPEAN SURGICAL RESEARCH J2 - EUR SURG RES VL - 58 PY - 2017 IS - 3-4 SP - 140 EP - 157 PG - 18 SN - 0014-312X DO - 10.1159/000453108 UR - https://m2.mtmt.hu/api/publication/3200784 ID - 3200784 LA - English DB - MTMT ER - TY - JOUR AU - Lauber, Dávid Tibor AU - Tihanyi, Dóra Krisztina AU - Czigány, Zoltán AU - Kovács, Tibor AU - Budai, András AU - Drozgyik, D AU - Fülöp, András AU - Szijártó, Attila TI - Liver regeneration after different degrees of portal vein ligation JF - JOURNAL OF SURGICAL RESEARCH J2 - J SURG RES VL - 203 PY - 2016 IS - 2 SP - 451 EP - 458 PG - 8 SN - 0022-4804 DO - 10.1016/j.jss.2016.03.032 UR - https://m2.mtmt.hu/api/publication/3096210 ID - 3096210 N1 - Lauber DT és Tihanyi Dóra Krisztina megosztott első szerzők AB - BACKGROUND: Selective portal vein ligation (PVL) is followed by ipsilateral atrophy and contralateral hypertrophy of the liver lobes. Although the atrophy-hypertrophy complex induced by PVL is a well-documented phenomenon, the effect of different degrees of extended portal vein occlusion on liver regeneration is not known. The aim of this study was to assess the effects of different degrees of portal occlusion on portal pressure and liver regeneration. MATERIALS AND METHODS: Male Wistar rats (n = 96; 220-250 g) were randomized into three groups and underwent 70%, 80%, or 90% portal vein ligation, respectively. The portal pressure was measured immediately and 24, 48, 72, 120, and 168 h after PVL (n = 6/group/time point). The hepatic lobes and the spleen were weighed, and liver regeneration ratio was calculated. Changes in liver histology and the mitotic activity were assessed on hematoxylin-eosin stained slides. RESULTS: Higher degree of portal occlusion triggered a stronger regenerative response (regeneration ratio of PVL 70%168h = 2.23 +/- 0.13, PVL 80%168h = 3.11 +/- 0.37, PVL 90%168h = 4.68 +/- 0.48) PVL led to an immediate increase in portal pressure, the value of which changed proportionally to the mass of liver tissue deprived of portal perfusion (PVL 70%acute = 17 +/- 2 mm Hg, PVL 80%acute = 19 +/- 1 mm Hg, PVL 90%acute = 26 +/- 4 mm Hg). Findings in histology showed necro-apoptotic lesions in the atrophic liver lobes and increased mitotic cell count in the hypertrophic lobes. The mitotic cell count of PVL 90% peaked earlier and at a significantly higher value than of PVL 70% and PVL 80% (PVL 9024h%: 96.0 +/- 3.5 PVL 70%48h: 64.0 +/- 2.1, PVL 80%48h: 56.3 +/- 4.0). The mitotic index after 24 h showed a strong correlation with the acute portal hypertension. CONCLUSIONS: A higher degree of portal vein occlusion leads to a greater regenerative response, presumably triggered by the proportional increase in portal pressure, which supports the role of the so-called "blood-flow" theory of PVL-triggered liver regeneration. LA - English DB - MTMT ER - TY - JOUR AU - Fülöp, András AU - Budai, András AU - Czigány, Zoltán AU - Lotz, Gábor AU - Dezső, Katalin AU - Paku, Sándor AU - Harsányi, László AU - Szijártó, Attila TI - Alterations in Hepatic Lobar Function in Regenerating Rat Liver JF - JOURNAL OF SURGICAL RESEARCH J2 - J SURG RES VL - 197 PY - 2015 IS - 2 SP - 307 EP - 317 PG - 11 SN - 0022-4804 DO - 10.1016/j.jss.2015.04.033 UR - https://m2.mtmt.hu/api/publication/2883410 ID - 2883410 N1 - 1st Department of Surgery, Semmelweis University, Ülloiút 78, Budapest, H-1082, Hungary Department of Pathology, Semmelweis University, Budapest, Hungary 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary Tumor Progression Research Group, Joint Research Organization of the Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary Cited By :4 Export Date: 17 February 2020 CODEN: JSGRA Correspondence Address: Szijártó, A.; 1st Department of Surgery, Semmelweis University, Ülloiút 78, Hungary LA - English DB - MTMT ER - TY - JOUR AU - Fülöp, András AU - Szijártó, Attila AU - Harsányi, László AU - Budai, András AU - Pekli, Damján AU - Korsós, D AU - Horváth, I AU - Stelczerné Kovács, Noémi AU - Karlinger, Kinga AU - Máthé, Domokos AU - Szigeti, Krisztián TI - Demonstration of Metabolic and Cellular Effects of Portal Vein Ligation Using Multi-Modal PET/MRI Measurements in Healthy Rat Liver JF - PLOS ONE J2 - PLOS ONE VL - 9 PY - 2014 IS - 3 PG - 9 SN - 1932-6203 DO - 10.1371/journal.pone.0090760 UR - https://m2.mtmt.hu/api/publication/2547916 ID - 2547916 N1 - Fülöp András és Szijártó Attila megosztott első szerzők Máthé Domokos és Szigeti Krisztián megosztott utolsó szerzők AB - OBJECTIVES: In the early recognition of portal vein ligation (PVL) induced tumor progression, positron emission tomography and magnetic resonance imaging (PET/MRI) could improve diagnostic accuracy of conventionally used methods. It is unknown how PVL affects metabolic patterns of tumor free hepatic tissues. The aim of this preliminary study is to evaluate the effect of PVL on glucose metabolism, using PET/MRI imaging in healthy rat liver. MATERIALS AND METHODS: Male Wistar rats (n = 30) underwent PVL. 2-deoxy-2-(18F)fluoro-D-glucose (FDG) PET/MRI imaging (nanoScan PET/MRI) and morphological/histological examination were performed before (Day 0) and 1, 2, 3, and 7 days after PVL. Dynamic PET data were collected and the standardized uptake values (SUV) for ligated and non-ligated liver lobes were calculated in relation to cardiac left ventricle (SUVVOI/SUVCLV) and mean liver SUV (SUVVOI/SUVLiver). RESULTS: PVL induced atrophy of ligated lobes, while non-ligated liver tissue showed compensatory hypertrophy. Dynamic PET scan revealed altered FDG kinetics in both ligated and non-ligated liver lobes. SUVVOI/SUVCLV significantly increased in both groups of lobes, with a maximal value at the 2nd postoperative day and returned near to the baseline 7 days after the ligation. After PVL, ligated liver lobes showed significantly higher tracer uptake compared to the non-ligated lobes (significantly higher SUVVOI/SUVLiver values were observed at postoperative day 1, 2 and 3). The homogenous tracer biodistribution observed before PVL reappeared by 7th postoperative day. CONCLUSION: The observed alterations in FDG uptake dynamics should be taken into account during the assessment of PET data until the PVL induced atrophic and regenerative processes are completed. LA - English DB - MTMT ER -