Sustained liver regeneration after portal vein embolization – A human molecular pilot study

Rauchfuß, F.; Lambeck, Sandro; Claus, Ralf A.; Ullmann, Janina; Schulz, Thomas F.; Weber, Martina; Katenkamp, Kathrin; Guthke, Reinhard; Bauer, Michael; Settmacher, Utz

doi:10.1016/j.dld.2012.04.002

Cited by 8 publications

(2 citation statements)

References 41 publications

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“…Although there were important discoveries revealed by previous studies indicated potential multiple signaling pathways and molecular genes or proteins that had been involved in the anti-tumor responses and other functions of emodin [8, 10, 34], the detailed molecular mechanisms by which this agent in anti-cancer effects still remained to be elucidated. Consistent with our previous study [11], we observed that emodin induced cell cycle arrest in G2/M phase checkpoint and reduced migration and invasion in lung cancer cells, which was in line with its widely established anti-tumor role of emodin [8-10, 35] implying the possibility of inhibition of both mitotic division and DNA replications which finally reduces cell division rates by emodin in this process. Thus, further testing the cell cycle related signaling pathways and proteins, such as cyclins, cyclin-dependent kinase inhibitors, p27/p21, and the detailed links of those molecules described above contributing to lung cancer cell growth inhibition are needed in the future.…”

Section: Discussionsupporting

confidence: 79%

Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

Tang¹,

Wu²,

Zheng³

et al. 2017

Cell Physiol Biochem

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Background: Emodin has anti-neoplastic activities on multiple tumors. However, the molecular mechanisms underlying this effect still remain to be fully understood. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays and flow cytometry, respectively. Cell invasion and migration were examined by transwell invasion and wound healing assays. Western blot analysis was performed to examine the phosphorylation and protein expression of AMP-activated protein kinase alpha (AMPKα), extracellular signaling-regulated kinase 1/2 (ERK1/2), peroxisome proliferators-activated receptor gamma (PPARγ), insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and the transcription factor Sp1. QRT-PCR was used to examine the mRNA levels of the IGFBP1 gene. Small interfering RNAs (siRNAs) were used to knockdown PPARγ and IGFBP1 genes. Exogenously expression of IGFBP1 and Sp1 was determined by transient transfection assays. IGFBP1 promoter activity was measured by Secrete-Pair Dual Luminescence Assay Kit. In vivo nude mice xenograft model and bioluminescent imaging system were used to confirm the findings. Results: We showed that emodin induced cell cycle arrest of NSCLC cells. Emodin increased PPARγ protein and luciferase reporter activity, which were abolished by inhibitors of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK)/ERK and AMPK. Silencing of PPARγ abrogated emodin-inhibited cell growth and cell cycle arrest. Furthermore, emodin elevated IGFBP1 mRNA, protein, and promoter activity through activation of PPARγ. Intriguingly, overexpressed Sp1 attenuated emodin-induced IGFBP1 expression, which was not observed in cells with silenced PPARγ gene. Moreover, silencing of IGFBP1 gene blunted emodin-induced inhibition of cell growth and cell cycle arrest. On the contrary, overexpressed IGFBP1 enhanced emodin-induced phosphorylation of AMPKα and ERK1/2, and restored emodin-inhibited growth in cells with silenced endogenous IGFBP1 gene. Emodin also inhibited growth of lung xenograft tumors and Sp1, and increased IGFBP1 and PPARγ protein expressions In vivo. Conclusion: Collectively, our results show that emodin inhibits growth of non-small-cell lung cancer (NSCLC) cells through ERK and AMPKα-mediated induction of PPARγ, followed by reduction of Sp1. This in turn induces IGFBP1 gene expression. Thus, the signaling cascades, positive feedback loop and cooperative interplay between transcription factors-induced the expression of IGFBP1 gene contribute to the overall responses of emodin. This study provides a novel mechanism by which emodin inhibits growth of human lung cancer cells.

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Section: Discussionsupporting

confidence: 79%

Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

Tang¹,

Wu²,

Zheng³

et al. 2017

Cell Physiol Biochem

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“…There are many regulatory factors playing a role in the regenerative process of liver parenchyma, such as hepatocyte growth factor (HGF), transforming growth factor-a (TGF-a), epidermal growth factors (EGF) and several cytokines. 39 -41 Additionally, it has been found that angiogenesis induced by vascular endothelial growth factor (VEGF) 42,43 and angiocrine growth factors 44 generate new blood vessels from pre-existing vessels, and in this way, these factors are instrumental in producing liver hypertrophy. 38 The increased vascular density (i.e.…”

Section: Discussionmentioning

confidence: 99%

Assessment of hepatic microvascular flow and density in patients undergoing preoperative portal vein embolization

İnce

Rassam

et al. 2019

HPB

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Beurteilung der Resektabilität kolorektaler Lebermetastasen und erweiterte Resektionen

Settmacher

Scheuerlein

Rauchfuß

2013

Chirurg

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Most patients with colorectal liver metastases are treated within a multimodal therapy regime whereby liver resection is a key point in the curative treatment concept. The achievement of an R0 situation is of vital importance for long-term survival. Besides general operability and the assessment of comorbidities, resection depends on the quality of liver parenchyma (functional resectability) and the anatomical position of the tumor (oncological resectability). The improvement of operation techniques and perioperative medicine nowadays allow complex surgical procedures for metastasis surgery. This article presents the methods for the assessment of resectability and modern strategies of preoperative conditioning as well as approaches for extended liver resection.

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Sustained liver regeneration after portal vein embolization – A human molecular pilot study

Cited by 8 publications

References 41 publications

Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

Assessment of hepatic microvascular flow and density in patients undergoing preoperative portal vein embolization

Beurteilung der Resektabilität kolorektaler Lebermetastasen und erweiterte Resektionen

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