Diagnose und multimodale Therapie des hepatozellulären Karzinoms

Kolligs, FT; Hoffmann, Ramona; Winkel, Mark op den; Bruns, C; Herrmann, Karin; Jakobs, Tobias; Lamerz, R.; Trumm, Christoph; Zech, CJ; Wilkowski, Ralf; Graeb, Christian

doi:10.1055/s-0028-1109901

Cited by 6 publications

(4 citation statements)

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“…This risk is particularly relevant before LT, as shown in the present analysis. Nowadays the sensitivity and specificity of noninvasive imaging studies in HCC suspicious lesions larger than 1 cm are both higher than 90% [38] and therefore biopsy is not routinely necessary [39, 40]. However, more than 20% of patients underwent tumor biopsy in the present series, even in more recent years.…”

Section: Discussionmentioning

confidence: 84%

Blood Transfusions and Tumor Biopsy May Increase HCC Recurrence Rates after Liver Transplantation

Seehofer

Öllinger

Denecke

et al. 2017

Journal of Transplantation

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Introduction. Beneath tumor grading and vascular invasion, nontumor related risk factors for HCC recurrence after liver transplantation (LT) have been postulated. Potential factors were analyzed in a large single center experience. Material and Methods. This retrospective analysis included 336 consecutive patients transplanted for HCC. The following factors were analyzed stratified for vascular invasion: immunosuppression, rejection therapy, underlying liver disease, age, gender, blood transfusions, tumor biopsy, caval replacement, waiting time, Child Pugh status, and postoperative complications. Variables with a potential prognostic impact were included in a multivariate analysis. Results. The 5- and 10-year patient survival rates were 70 and 54%. The overall 5-year recurrence rate was 48% with vascular invasion compared to 10% without (p < 0.001). Univariate analysis stratified for vascular invasion revealed age over 60, pretransplant tumor biopsy, and the application of blood transfusions as significant risk factors for tumor recurrence. Blood transfusions remained the only significant risk factor in the multivariate analysis. Recurrence occurred earlier and more frequently in correlation with the number of applied transfusions. Conclusion. Tumor related risk factors are most important and can be influenced by patient selection. However, it might be helpful to consider nontumor related risk factors, identified in the present study for further optimization of the perioperative management.

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Section: Discussionmentioning

confidence: 84%

Blood Transfusions and Tumor Biopsy May Increase HCC Recurrence Rates after Liver Transplantation

Seehofer

Öllinger

Denecke

et al. 2017

Journal of Transplantation

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“…Mice were divided into the following 4 groups (n=7/group) on the 5th day after injection when the tumor volume of HepG2 cells reached ~50 mm 3 : i) Model group (injected with cancer cells and administered intragastrically with the equivalent volume of 0.5% carboxymethylcellulose sodium, served as the negative control); ii) curcumin low dose group (Cur L; injected with cancer cells and administered intragastrically with 120 mg/kg curcumin daily); iii) curcumin high dose group (Cur H; injected with cancer cells and administered intragastrically with 240 mg/kg curcumin daily); and iv) chemotherapy group (injected with cancer cells and intraperitoneally injected with 50 mg/kg 5-Fu + 5 mg/kg DDP once a week; positive control). The regimens of 5-Fu+DDP and curcumin were based on their clinical application and a previous study, respectively (32,33). Furthermore, 240 mg/kg curcumin used in mice is equivalent to ~1.3 g/day in humans based on the body surface area (m 2 /kg) conversion between humans and mice, with a postulated adult body weight of 75 kg (human dosage=(240 mg/kg/14.16) x75 kg), which was considered safe for humans according to a phase I clinical trial (34).…”

Section: Methodsmentioning

confidence: 99%

Curcumin inhibits the growth of liver cancer by impairing myeloid‑derived suppressor cells in murine tumor tissues

et al. 2021

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Curcumin, one of the active ingredients of Curcuma longa (Jianghuang), has been reported to exert multiple bioactivities, including pro-apoptotic and anti-inflammatory activities. In recent years, curcumin has been extensively studied, and it has been revealed that curcumin inhibits the growth of numerous types of cancer. However, to the best of our knowledge, the inhibitory effects of curcumin on the activation or expansion of myeloid-derived suppressor cells (MDSCs) in liver cancer and the underlying mechanism have not yet been determined. Therefore, the present study aimed to investigate the inhibitory effect of curcumin on MDSC activity and the associated anti-neoplastic mechanism in a HepG2 ×enograft mouse model. The effect of curcumin on the viability of Huh-7, MHCC-97H and HepG2 cells in vitro was analyzed using a Cell Counting Kit-8 assay. The effects of curcumin on tumor growth, numbers of MDSCs, expression levels of proteins involved in the toll-like receptor 4 (TLR4)/NF-κB signaling pathway, levels of related inflammatory factors and angiogenesis were determined in HepG2 ×enograft model mice, which were given different doses of curcumin via intragastrical administration. The results of the present study revealed that curcumin inhibited the viability of Huh-7, MHCC-97H and HepG2 cells and the growth of HepG2 ×enograft tumors in mice. Flow cytometric analysis indicated that curcumin reduced the number of MDSCs in mouse xenograft tumors. In addition, the results demonstrated that curcumin inhibited the TLR4/NF-κB signaling pathway and the expression of inflammatory factors, including IL-6, IL-1β, prostaglandin E2 and cyclooxygenase-2, in mouse xenograft tumors. Furthermore, curcumin suppressed the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony stimulating factor (G-CSF), which are essential factors for MDSCs modulation, in tumor tissues. Additionally, curcumin was revealed to inhibit angiogenesis, which was demonstrated by the downregulation of the expression levels of vascular endothelial growth factor, CD31 and α-smooth muscle actin in western blotting, immunohistochemistry and immunofluorescence experiments. In conclusion, the findings of the present study identified a novel mechanism via which curcumin may suppress the growth of liver cancer by reducing the numbers of MDSCs and subsequently disrupting the process of angiogenesis. These conclusions were supported by the observed inactivation of the TLR4/NF-κB signaling pathway-mediated inflammatory response and the downregulation of GM-CSF and G-CSF secretion in xenograft tissues.

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“…Only 10–20% of HCC cases are suitable for resection, with a 5-year recurrence-free survival of only 20–30% [3, 4]. Recent developments in new treatment modalities have led to an improved survival rate slightly [5]; however, current treatments are still not satisfactory, and thus, novel treatment strategies against HCC are in dire need.…”

Section: Introductionmentioning

confidence: 99%

1, 25(OH)<sub>2</sub>D<sub>3</sub> Inhibits Hepatocellular Carcinoma Development Through Reducing Secretion of Inflammatory Cytokines from Immunocytes

Guo¹,

Ma²,

Ma³

et al. 2013

CMC

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Epidemiological and clinical studies have indicated that low vitamin D activity is not only associated with an increased cancer risk and a more aggressive tumor growth, but also connected with an aggravated liver damage caused by chronic inflammation. Meanwhile, increasing evidence has demonstrated that 1,25(OH)2D3 (the most biologically active metabolite of vitamin D) can inhibit inflammatory response in some chronic inflammatory associated cancer, which is considered to have the anti-tumor potency. However, the interaction between 1,25(OH)2D3 and inflammation during hepatocellular carcinoma (HCC) initiation and progression is not yet clear. Here, we report an anti-tumorigenesis effect of 1,25(OH)2D3 via decreasing inflammatory cytokine secretion in HCC and hypothesize the possible underlying mechanism. Firstly, we show that the enhanced tumor growth is associated with elevated inflammatory cytokine IL-6 and TNF-α in 1α(OH)ase gene-knockout mice. Secondly, 1,25(OH)2D3 can inhibit vitamin D receptor (VDR) shRNA interfered tumor cell growth through decreasing inflammatory cytokine secretion in vitro and in vivo. Finally, using p27kip1 gene knock-out mouse model, we demonstrate that the effect of 1,25(OH)2D3 in inhibiting immune cell related inflammatory cytokine secretion, exerts in a p27kip1 gene dependent way. Collectively, 1,25(OH)2D3 inhibits HCC development through up-regulating the expression of p27kip1 in immune cell and reducing inflammatory cytokine production.

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Diagnose und multimodale Therapie des hepatozellulären Karzinoms

Cited by 6 publications

References 50 publications

Blood Transfusions and Tumor Biopsy May Increase HCC Recurrence Rates after Liver Transplantation

Blood Transfusions and Tumor Biopsy May Increase HCC Recurrence Rates after Liver Transplantation

Curcumin inhibits the growth of liver cancer by impairing myeloid‑derived suppressor cells in murine tumor tissues

1, 25(OH)<sub>2</sub>D<sub>3</sub> Inhibits Hepatocellular Carcinoma Development Through Reducing Secretion of Inflammatory Cytokines from Immunocytes

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