A small mammal model of tumour implantation, dissemination and growth factor expression after partial hepatectomy

Aalbers, Arend G. J.; Kate, Miranda ten; Grevenstein, Wilhelmina M U van; Hofland, Leo J.; Wiemer, Erik A.C.; Jeekel, J.; Eijck, Casper H.J. van

doi:10.1016/j.ejso.2007.02.035

Cited by 5 publications

(5 citation statements)

References 32 publications

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“…Moreover, previous in vivo studies with CC531s cells showed that either local or systemic trauma did not enhance growth of established peritoneal metastases. In contrast, enhanced tumor development was observed when tumor cell suspension was injected during the operation 5, 38. This suggests that implantation of tumor cells, but not growth, was facilitated by the operation.…”

Section: Discussionmentioning

confidence: 91%

Blocking α2 integrins on rat CC531s colon carcinoma cells prevents operation-induced augmentation of liver metastases outgrowth

et al. 2007

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Section: Discussionmentioning

confidence: 91%

Blocking α2 integrins on rat CC531s colon carcinoma cells prevents operation-induced augmentation of liver metastases outgrowth

et al. 2007

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“…Angiogenesis is necessary for the restoration of liver structure and function (101) but is also crucial for tumour growth and metastases (102). Liver resection increases the levels of angiogenic factors such as VEGF, basic‐fibroblast growth factor and hypoxia‐inducible factor‐1α (65, 66, 103, 104) as well as potent growth factors such as HGF, epidermal growth factor, heparin‐binding epidermal growth factor, TGF‐α and insulin‐like growth factor1 along with their receptors (105, 106). These factors regulate the key processes associated with liver regeneration including angiogenesis, cellular proliferation and ECM remodelling, all of which are also hallmarks of tumour growth and metastasis (103, 105, 107–109).…”

Section: Effects Of the Regenerating Process On Tumour Growthmentioning

confidence: 99%

Liver regeneration and tumour stimulation: implications of the renin-angiotensin system

Koh¹,

Ager²,

Christophi³

2010

Liver International

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Liver resection is the most effective treatment for primary liver tumours and metastasis to the liver, and remains the only potentially long-term curative therapy for patients with colorectal cancer (CRC) liver metastases. Nevertheless, there is a significant incidence of tumour recurrence following liver resection. Cellular and molecular changes resulting from resection and the subsequent liver regeneration process may influence the kinetics of tumour growth, contributing to recurrence. Although commonly associated with the systemic homeostasis of blood pressure, fluid and electrolyte, the reninangiotensin system (RAS) has recently been shown to play a role in regulating cell proliferation, apoptosis and angiogenesis in local organs as well as in malignancies. An electronic search of the English literature on the role of the RAS in liver regeneration and tumourigenesis was performed using PubMed, with additional relevant articles sourced from reference lists. Studies have shown that the blockade of the RAS pathway stimulates liver regeneration and inhibits tumour progression. An understanding of the role of RAS in liver regeneration and tumourigenesis may enable alternative strategies to improve patient outcome and survival after liver resection. This review will discuss the role of the RAS in liver regeneration and in tumour recurrence post-liver resection. The potential of the RAS as a novel therapeutic target for CRC liver metastases patients undergoing liver resection will be outlined.As the liver is one of the few organs that has the ability to regenerate to its full capacity and function, liver resection has been performed to remove benign or malignant lesions of the liver in cancer patients (1). Liver resection is currently used to treat hepatocellular carcinoma patients with a well-preserved hepatic function as well as patients with colorectal cancer (CRC) liver metastases. Liver resection remains the most appropriate and effective treatment in the removal of primary liver tumours and it is the only therapy that offers a potential long-term cure for patients with CRC liver metastases (2, 3). Worldwide, hepatocellular carcinoma is the fifth most common cancer and it is the leading cause of cancer death in many areas (2). CRC is the second leading cause of death across both genders worldwide, and in the USA alone, approximately 150 000 cases of CRC are diagnosed annually, resulting in 50 000 deaths (4-6). The majority of CRCrelated deaths are associated with liver metastasis, which occurs in up to 70% of patients with CRC (7,8).Currently, curative therapy is achieved in 20-60% of patients by liver resection in conjunction with chemotherapy (4, 7). The incidence of post-operative complications, mortality rate and the number of days of ICU post-resection correlate directly with the number of hepatic segments resected (8). Post-operative complications occur in 5-40% of patients and mortality following liver resection is almost exclusively because of liver failure resulting from inadequate post-operat...

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“…Four days after adenovirus transfection, a 30% partial hepatectomy was performed in rats in the miR‐203+PH group, the miR‐NC+PH group and the PH group. PH was performed as described previously . In brief, hilar vessels of the left lobe of the liver were ligated and the ligated lobe was subsequently excised.…”

Section: Methodsmentioning

confidence: 99%

“…PH was performed as described previously. (13) In brief, hilar vessels of the left lobe of the liver were ligated and the ligated lobe was subsequently excised. Portions of the hepatic parenchyma equal to 30% of the total liver were removed in this manner.…”

Section: Methodsmentioning

confidence: 99%

miR‐203 inhibits augmented proliferation and metastasis of hepatocellular carcinoma residual in the promoted regenerating liver

Zheng

Chen

et al. 2017

Cancer Science

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Liver resection is still the most commonly used therapeutic treatment for hepatocellular carcinoma (HCC), and liver regeneration promotes HCC growth in the regenerating liver. The high recurrence/metastasis of HCC is the main cause of death for HCC patients after liver resection. However, how the augmented growth and metastasis of residual HCC induced by the promoted liver regeneration following liver resection can be abolished remains unclear. In this study, a rat model with liver cirrhosis and diffused HCC was established by administration of diethylnitrosamine. Recombinant miR‐203 adenovirus was administered to induce hepatic miR‐203 overexpression and 30% partial hepatectomy (PH) followed. The effect of miR‐203 on the proliferation, invasion and metastasis of the residual HCC in the remnant cirrhotic liver with promoted regeneration was investigated. We found that the basic spontaneous regeneration of the non‐tumorous liver by 30% PH promoted proliferation, invasion and lung metastasis of the hepatic residual HCC. miR‐203 overexpression further promoted the regeneration of the non‐tumorous liver by upregulating Ki67 expression and enhancing IL‐6/SOCS3/STAT3 pro‐proliferative signals. Importantly, miR‐203 overexpression markedly inhibited the proliferation, invasion and metastasis of hepatic residual HCC through suppressing expression of Ki67, CAPNS1 and lung metastasis. Moreover, it was found that miR‐203 overexpression reversed the epithelial–mesenchymal transition induced by hepatectomy through targeting IL‐1β, Snail1 and Twist1. In conclusion, our results suggested that miR‐203 overexpression inhibited the augmented proliferation and lung metastasis of the residual HCC induced by the promoted liver regeneration following PH partly by regulating epithelial–mesenchymal transition.

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A small mammal model of tumour implantation, dissemination and growth factor expression after partial hepatectomy

Cited by 5 publications

References 32 publications

Blocking α2 integrins on rat CC531s colon carcinoma cells prevents operation-induced augmentation of liver metastases outgrowth

Blocking α2 integrins on rat CC531s colon carcinoma cells prevents operation-induced augmentation of liver metastases outgrowth

Liver regeneration and tumour stimulation: implications of the renin-angiotensin system

miR‐203 inhibits augmented proliferation and metastasis of hepatocellular carcinoma residual in the promoted regenerating liver

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