Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats

Olsen, Peter Skov; Boesby, S; Kirkegaard, Preben; Therkelsen, Kim; Almdal, Thomas; Poulsen, Steen Seier; Nexø, Ebba

doi:10.1002/hep.1840080503

Cited by 138 publications

(43 citation statements)

References 22 publications

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“…11-13 TGF-␣ and EGF are known to be potent stimulators of hepatocyte proliferation. [14][15][16][17] During liver regeneration, TGF-␣ levels increase in liver tissue in rats and in serum in humans. 16,18,19 Moreover, these growth factors and their receptor (EGFr) have been described to determine tumor behavior in human colorectal cancer cells in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of transforming growth factor α, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors

et al. 1998

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To determine whether the expression of transforming growth factor ␣ (TGF-␣), its receptor (epidermal growth factor receptor [EGFr]), p53 nuclear protein, and proliferation influences prognosis of patients with liver metastases, a study was performed in 45 liver metastases and 33 corresponding primary colorectal carcinomas in patients referred for liver surgery. The expression of TGF-␣, EGFr, p53 nuclear protein, and proliferation rate was correlated with clinicopathological characteristics and survival after partial liver resection. In liver metastases, TGF-␣ expression was low in 42%, intermediate in 35%, and high in 23%. TGF-␣ expression was higher in liver metastases derived from lymph node-positive primary carcinomas, in synchronous and in irresectable liver metastases compared with those derived from lymph node-negative primary carcinomas, metachronous, and resectable liver metastases. Nuclear p53 expression was found in 83% of primary tumors and 71% of liver metastases. p53 expression did not correlate with the various clinicopathological characteristics. Ki67 expression was not associated with clinicopathological characteristics in primary and metastatic tumors. In the 38 patients in whom a partial liver resection was performed, median survival was 25 months in patients with a higher TGF-␣ expression in the metastasis than in the primary tumor and 60 months in patients with comparable or lower TGF-␣ expression in the metastasis than in the primary tumor (P ‫؍‬ .036). Median survival after liver resection was 21 months in patients with p53-negative liver metastases and 58 months in patients with p53-positive metastases (P ‫؍‬ .043). By multivariate analysis, p53 and EGFr expression on liver metastases were the best predictors of diseasefree survival after partial liver resection, with relative risks of 2.38 and 3.33, respectively. In patients with colorectal liver metastases, referred for liver surgery, a higher TGF-␣ expression is associated with unfavorable tumor characteristics, whereas p53 and absence of EGFr expression is associated with a better survival after partial liver resection. (HEPATOLOGY 1998;28:971-979.)Colorectal carcinoma is the second-leading cause of cancer deaths in the Western community. Of all colorectal cancer patients, about 50% will die within 5 years after diagnosis. 1 At the time of initial diagnosis, 15% to 25% of patients present with synchronous liver metastases. 1 It is estimated that overall, only 5% of patients who develop liver metastases of colorectal carcinomas are amenable to partial liver resection. 2 Despite intentionally curative liver resections, only 20% to 30% of these patients have a disease-free 5-year survival. [3][4][5] Furthermore, in patients with recurrences after liver resection, these recurrences often appear early after liver surgery, with the liver being a frequent site of initial failure. 5,6 In the animal model, tumor growth can be influenced by growth factors produced by the tumor cells and by growth factors generated by the organ that harbors the m...

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Section: Discussionmentioning

confidence: 99%

Clinical relevance of transforming growth factor α, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors

et al. 1998

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“…It was reported that HSS alone had little effect on the DNA synthesis of the resting hepatocytes as in the primary culture hepatocytes, but in contrast, if combined with EGF, it could amplify the growth response of the cells to EGF both in vitro [20,21] and in vivo [22]. The EGF participation in the regulation of liver proliferation was demonstrated in the down-regulation of EGF receptor following partial hepatectomy [23].…”

Section: Discusionmentioning

confidence: 99%

Growth induction of hepatic stimulator substance in he-patocytes through its regulation on EGF receptors

Liu

Lei

et al. 1999

Cell Res

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The cytosolic liver-specific growth factor-hepatic stimulator substance (HSS) has been shown to be able to amplify the rat hepatocyte proliferation responded to EGF. In order to get more insight into the mechanism, the regulatory effect of HSS on EGF-receptor (EGF-R) and the receptor phosphorylation at molecular level was studied. HSS partially purified from weanling rat liver was given to cultured hepatocytes and its influence on EGF-R specific binding and internalization as well as mRNA expression were investigated. The results showed that preincubation of hepatocytes with HSS could lead to an increase in [ 125 I]-EGF binding to its receptors and inhibit EGFinduced receptor down-regulation. Furthermore, the over-expression of EGF-R mRNA stimulated by HSS was seen during 2-12 h after the incubation. Additionally, it was demonstrated with human hepatoma SMMC-7721 cells in Western blot that the EGF-R expression and the receptorautophosphorylation were increased with dose/time-dependency after HSS treatment . These results strongly suggest that the mechanism of HSS action on hepatocyte growth might be related to its modulation on EGF-R and receptor-mediated signaling transduction .

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“…During the last decade, evidence has been collected on the central role played by growth stimulating factors (GsF) [1][2][3][4][5][6][7][8][9] and growth inhibiting factors (GiF) [10][11][12] in the mechanism of tissue growth regulation, using different experimental models [13]. The model of partial hepatectomy (PH) in rats has provided numerous findings on the existence of this regulatory process.…”

Section: Introductionmentioning

confidence: 99%

“…Transforming growth factor alpha, hepatocyte (H)GF, and epidermal (E)GF, which are defined as progressors, induce the G 0 -G 1 transition and allow hepatocytes to progress throughout the cell cycle. These GFs act both in vivo and in vitro [5,7,9]. H-ras, K-ras, and p53 are the biological markers of G 1 -S progression [11].…”

Section: Introductionmentioning

confidence: 99%

Hepatic regeneration and growth factors

et al. 1993

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Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats

Cited by 138 publications

References 22 publications

Clinical relevance of transforming growth factor α, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors

Clinical relevance of transforming growth factor α, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors

Growth induction of hepatic stimulator substance in he-patocytes through its regulation on EGF receptors

Hepatic regeneration and growth factors

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