Liver Regeneration and Tumor Stimulation—A Review of Cytokine and Angiogenic Factors

Christophi, Christopher; Harun, Nadia; Fifis, Theodora

doi:10.1007/s11605-007-0459-6

Cited by 52 publications

(42 citation statements)

References 173 publications

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“…Replication of hepatocytes generally starts within 1 d after major resection in both rodents and humans. This is predominantly due to that the hepatocytes go from the quiescent [48,50,53,54] , but demonstrate a similar synchronicity in DNA synthesis and mitosis as seen in hepatocytes [48] . Accompanying the cellular replication, there is also a breakdown and remodeling of the extracellular matrix (ECM), promoted by cell-ECM interactions, which is also of vital importance in regulating liver regeneration [55] .…”

Section: Liver Regenerationmentioning

confidence: 84%

“…Liver regeneration is a reparative process following parenchymal damage or surgical resection of the liver [48] . The compensatory process of hepatic regeneration involves numerous cells and molecules (cytokines and growth factors) that mediate their role through multiple molecular pathways [48][49][50][51][52] (Table 1). The progression of liver regeneration is segmented roughly in three phases: priming (G0 to G1 phase), proliferation (G1 to M phase) and termination.…”

Section: Liver Regenerationmentioning

confidence: 99%

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Effect of liver regeneration on malignant hepatic tumors

Shi

Line

2014

WJG

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Liver regeneration after major surgery may activate occult micrometastases and facilitate tumor growth, leading to liver tumor recurrence. Molecular changes during liver regeneration can provide a microenvironment that stimulates intrahepatic tumor propagation through alterations in cellular signaling pathways, where activation and proliferation of mature hepatocytes, hepatic progenitor cells, non-parenchymal liver cells might favor both liver regeneration and tumor growth. This review highlights recent advances of tumor growth and development in the regenerating liver, possible mechanisms and clinical implications. Key words: Hepatocellular carcinoma; Colorectal cancer; Recurrence; Liver regeneration; Hepatic progenitor cell; Epithelial to mesenchymal transition Core tip: The liver has a unique capacity for regeneration after cellular damage or partial removal of tissue, and modern liver surgery relies on this property. Liver regeneration is a complex process involving a large array of growth factors, cytokines and cells to restore hepatic mass and function. Experimental and clinical data indicate that the regeneration signals facilitate the growth of both primary and secondary liver tumors and can alter their malignant potential. This is an important mechanism underlying recurrence after liver surgery. New therapeutic strategies founded on better insight into the relationship between liver regeneration and tumor biology are needed.Shi JH, Line PD. Effect of liver regeneration on malignant hepatic tumors.

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Section: Liver Regenerationmentioning

confidence: 84%

Section: Liver Regenerationmentioning

confidence: 99%

Effect of liver regeneration on malignant hepatic tumors

Shi

Line

2014

WJG

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“…1), biliary epithelial cells, liver sinusoidal endothelial cells (LSECs), Kupffer cells, and hepatic stellate cells (HSCs, which are pericytes in the liver) [19]. Liver regeneration undergoes three stages [12]. The first is the priming stage and occurs during the first few hours after PH.…”

Section: The Process Of Liver Regenerationmentioning

confidence: 99%

“…Many specific factors involved in liver regeneration are believed to be able to influence the growth of residual or dormant micrometastases after PH, and also modulating tumor angiogenesis [12]. These factors include hepatocyte growth factor (HGF), epidermal growth factor (EGF), transforming growth factor (TGF)-a, TGF-b, hypoxia-inducible factor 1 (HIF-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs).…”

Section: Introductionmentioning

confidence: 99%

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Angiogenesis: multiple masks in hepatocellular carcinoma and liver regeneration

Chen

Shi

et al. 2010

Hepatol Int

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Hepatocellular carcinoma (HCC) is naturally resistant to radiotherapy and cytotoxic chemotherapy, leaving surgery as the mainstream therapeutic approach. However, the 5-year recurrence rate after curative resection is as high as 61.5%. The background hepatitis B-or C-induced cirrhosis and the presence of micrometastases at the time of surgery have been regarded as two main causes of recurrence. Recently, accumulating evidence suggests that growth factors and cytokines released during the physiological process of post-surgical liver regeneration could induce the activation of dormant micrometastatic lesions. The establishment of neovasculature to support either liver regeneration or HCC growth involves multiple cell types including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and circulating endothelial progenitors. The crosstalks among these cells are driven by multiple molecules and signaling pathways, including vascular endothelial growth factors and their receptors, platelet-derived growth factor, the angiopoietin/Tie family, hepatocyte growth factor/c-Met signaling, and others. Anti-angiogenic agent targeting liver cancer vasculature has been reported to be able to generate limited survival benefit of the patients. In this review, discussions are focused on various angiogenic mechanisms of HCC and liver regeneration, as well as the prevailing anti-angiogenic strategies.

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Injectable Hydrogels for Liver: Potential for Clinical Translation

Vasudevan,

Ghosal,

Ram Sahu

et al. 2024

Chemistry An Asian Journal

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Injectable hydrogels are a sub‐type of hydrogels which can be delivered into the host in a minimally invasive manner. They can act as carriers to encapsulate and deliver cells, drugs or active biomolecules across several disease conditions. Polymers, either synthetic or natural, or even a combination of the two, can be used to create injectable hydrogels. Clinically approved injectable hydrogels are being used as dressings for burn wounds, bone and cartilage reconstruction. Injectable hydrogels have recently gained tremendous attention for their delivery into the liver in pre‐clinical models. However, their efficacy in clinical studies remains yet to be established. In this article, we describe principles for the design of these injectable hydrogels, delivery strategies and their potential applications in facilitating liver regeneration and ameliorating injury. We also discuss the several constraints related to translation of these hydrogels into clinical settings for liver diseases and deliberate some potential solutions to combat these challenges.

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Liver Regeneration and Tumor Stimulation—A Review of Cytokine and Angiogenic Factors

Cited by 52 publications

References 173 publications

Effect of liver regeneration on malignant hepatic tumors

Effect of liver regeneration on malignant hepatic tumors

Angiogenesis: multiple masks in hepatocellular carcinoma and liver regeneration

Injectable Hydrogels for Liver: Potential for Clinical Translation

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