Normal Liver Regeneration after Partial Liver Radiation: An Experimental Study on Rats

Author(s):  
J.D. Zhao ◽  
G.L. Jiang
Hepatology ◽  
2003 ◽  
Vol 38 ◽  
pp. 598-598
Author(s):  
O GOLDSHMIDT ◽  
R YEIKILIS ◽  
M PAIZI ◽  
I VLODAVSKY ◽  
G SPIRA

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16115-e16115
Author(s):  
Ting-Shi Su ◽  
Li-Qing Li ◽  
Shi-Xiong Liang

e16115 Background: In the past clinical practice of radiotherapy for liver cancer, liver regeneration (LR) which is beneficial to the prevention or recovery of radiation-induced liver injury, has not received enough attention. In current study, we aimed to build and validate multivariate model for liver regeneration after radiation therapy for hepatocellular carcinoma (HCC) based on data from 2 prospective studies. Methods: Thirty patients treated with preoperative downstaging radiotherapy were prospectively included in the training cohort, and 21 patients treated with postoperative adjuvant radiotherapy were included in the validation cohort. Liver regeneration was defined as an increase of more than 10% of normal liver volume in the areas of the protected hepatic segment or lobe, without Child-Pugh class decreased and tumor progression compared to pre-radiotherapy. Model and nomogram of liver regeneration after radiotherapy were developed and validated. The cut-off points of each optimal predictors were obtained using receiver-operating characteristic analysis. Risk stratification based on the cut-off point was conducted to compare the proportion of patients with liver regeneration between subgroups. Results: After radiotherapy, 12 (40%) cases in the training cohort and 13 (61.9%) cases in the validation cohort experienced liver regeneration. The model and nomogram of liver regeneration based on SVs20 (standard residual liver volume spared from at least 20 Gy) and alanine aminotransferase (ALT) showed good prediction performance (AUC = 0.759) in training cohort and performed well (AUC = 0.808) in the validation cohort. The risk stratification according to the cutoffs of SVs20 with 303.4 mL and ALT with 43 U/L demonstrated clear differentiation in risk of liver regeneration between the training(P = 0.049) and entire cohort (P = 0.032). The proportion of patients with liver regeneration decrease progressively with 88.9% in high-probability group (ALT<43 U/L and SVs20<303.4 mL), 60% in high-intermediate probability group (ALT ≥43 U/L and SVs20<303.4 mL), 43.75% in low-intermediate probability group (ALT<43 U/L and SVs20≥303.4 mL) and 33% in low- probability group (ALT≥43 U/L and SVs20≥303.4 mL). Conclusions: SVs20 and ALT are optimal predictors for liver regeneration. This simple-to-use nomogram is beneficial to the constraints of normal liver outside the radiotherapy target area and make prognosis-based decision without complex calculations. Clinical trial information: ChiCTR1800015350. [Table: see text]


HPB ◽  
2019 ◽  
Vol 21 ◽  
pp. S667
Author(s):  
K.J. Andersen ◽  
A.R. Knudsen ◽  
B.N. Jepsen ◽  
M. Meier ◽  
A.P.A. Gunnarsson ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yachao Tao ◽  
Menglan Wang ◽  
Enqiang Chen ◽  
Hong Tang

Liver regeneration is a highly organized tissue regrowth process and is the most important reaction of the liver to injury. The overall process of liver regeneration includes three phases: priming stage, proliferative phase, and termination phase. The initial step aims to induce hepatocytes to be sensitive to growth factors with the aid of some cytokines, including TNF-α and IL-6. The proliferation phase promotes hepatocytes to re-enter G1 with the stimulation of growth factors. While during the termination stage, hepatocytes will discontinue to proliferate to maintain normal liver mass and function. Except for cytokine- and growth factor-mediated pathways involved in regulating liver regeneration, new substances and technologies emerge to influence the regenerative process. Here, we reviewed novel and important signaling molecules involved in the process of liver regeneration to provide a cue for further research.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
David A. Rudnick ◽  
Nicholas O. Davidson

The regenerative capacity of the liver is well known, and the mechanisms that regulate this process have been extensively studied using experimental model systems including surgical resection and hepatotoxin exposure. The response to primary mitogens has also been used to investigate the regulation of hepatocellular proliferation. Such analyses have identified many specific cytokines and growth factors, intracellular signaling events, and transcription factors that are regulated during and necessary for normal liver regeneration. Nevertheless, the nature and identities of the most proximal events that initiate hepatic regeneration as well as those distal signals that terminate this process remain unknown. Here, we review the data implicating acute alterations in lipid metabolism as important determinants of experimental liver regeneration and propose a novel metabolic model of regeneration based on these data. We also discuss the association between chronic hepatic steatosis and impaired regeneration in animal models and humans and consider important areas for future research.


Hepatology ◽  
2017 ◽  
Vol 65 (4) ◽  
pp. 1384-1392 ◽  
Author(s):  
George K. Michalopoulos

2010 ◽  
Vol 207 (6) ◽  
pp. 1197-1208 ◽  
Author(s):  
Karen J. Ho ◽  
Nhue L. Do ◽  
Hasan H. Otu ◽  
Martin J. Dib ◽  
Xianghui Ren ◽  
...  

How proliferative and inhibitory signals integrate to control liver regeneration remains poorly understood. A screen for antiproliferative factors repressed after liver injury identified transducer of ErbB2.1 (Tob1), a member of the PC3/BTG1 family of mito-inhibitory molecules as a target for further evaluation. Tob1 protein decreases after 2/3 hepatectomy in mice secondary to posttranscriptional mechanisms. Deletion of Tob1 increases hepatocyte proliferation and accelerates restoration of liver mass after hepatectomy. Down-regulation of Tob1 is required for normal liver regeneration, and Tob1 controls hepatocyte proliferation in a dose-dependent fashion. Tob1 associates directly with both Caf1 and cyclin-dependent kinase (Cdk) 1 and modulates Cdk1 kinase activity. In addition, Tob1 has significant effects on the transcription of critical cell cycle components, including E2F target genes and genes involved in p53 signaling. We provide direct evidence that levels of an inhibitory factor control the rate of liver regeneration, and we identify Tob1 as a crucial check point molecule that modulates the expression and activity of cell cycle proteins.


2007 ◽  
Vol 83 (10) ◽  
pp. 699-706 ◽  
Author(s):  
Jorge E. Cardoso ◽  
Veronica A. Trivillin ◽  
Elisa M. Heber ◽  
David W. Nigg ◽  
Osvaldo Calzetta ◽  
...  

2013 ◽  
Vol 54 (4) ◽  
pp. 893-908 ◽  
Author(s):  
Igor O. Shmarakov ◽  
Hongfeng Jiang ◽  
Kryscilla Jian Zhang Yang ◽  
Ira J. Goldberg ◽  
William S. Blaner

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