Impact of body composition on survival and morbidity after liver resection in hepatocellular carcinoma patients

Kroh, Andreas; Uschner, Diane; Lodewick, Toine M.; Eickhoff, Roman; Schöning, Wenzel; Ulmer, Florian; Neumann, Ulf; Binnebösel, Marcel

doi:10.1016/j.hbpd.2018.07.008

Cited by 39 publications

(52 citation statements)

References 48 publications

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“…For the longest time, the frailty and pronounced muscle weakness that characterizes the majority of HCC patients received much less attention. This has significantly changed in recent years as reports were published from independent groups about the important role of sarcopenia and cachexia in predicting both clinical course and response to therapy of HCC patients . Cachexia is widely considered to be a multifactorial syndrome with various manifestations throughout the whole body.…”

Section: Discussionmentioning

confidence: 99%

“…This has significantly changed in recent years as reports were published from independent groups about the important role of sarcopenia and cachexia in predicting both clinical course and response to therapy of HCC patients. 4,[39][40][41] Cachexia is widely considered to be a multifactorial syndrome with various manifestations throughout the whole body. The causal pathogenesis of cachexia is very complex and involves a plethora of organs, cell types, hormones, cytokines/chemokines, growth factors, and interorgan crosstalks.…”

Section: Discussionmentioning

confidence: 99%

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Macrophages protect against loss of adipose tissue during cancer cachexia

Erdem

Möckel

Jumpertz

et al. 2019

J cachexia sarcopenia muscle

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BackgroundCancer cachexia represents a central obstacle in medical oncology as it is associated with poor therapy response and reduced overall survival. Systemic inflammation is considered to be a key driver of cancer cachexia; however, clinical studies with anti‐inflammatory drugs failed to show distinct cachexia‐inhibiting effects. To address this contradiction, we investigated the functional importance of innate immune cells for hepatocellular carcinoma (HCC)‐associated cachexia.MethodsA transgenic HCC mouse model was intercrossed with mice harbouring a defect in myeloid cell‐mediated inflammation. Body composition of mice was analysed via nuclear magnetic resonance spectroscopy and microcomputed tomography. Quantitative PCR was used to determine adipose tissue browning and polarization of adipose tissue macrophages. The activation state of distinct areas of the hypothalamus was analysed via immunofluorescence. Multispectral immunofluorescence imaging and immunoblot were applied to characterize sympathetic neurons and macrophages in visceral adipose tissue. Quantification of pro‐inflammatory cytokines in mouse serum was performed with a multiplex immunoassay. Visceral adipose tissue of HCC patients was quantified via the L3 index of computed tomography scans obtained during routine clinical care.ResultsWe identified robust cachexia in the HCC mouse model as evidenced by a marked loss of visceral fat and lean mass. Computed tomography‐based analyses demonstrated that a subgroup of human HCC patients displays reduced visceral fat mass, complementing the murine data. While the myeloid cell‐mediated inflammation defect resulted in reduced expression of pro‐inflammatory cytokines in the serum of HCC‐bearing mice, this unexpectedly did not translate into diminished but rather enhanced cachexia‐associated fat loss. Defective myeloid cell‐mediated inflammation was associated with decreased macrophage abundance in visceral adipose tissue, suggesting a role for local macrophages in the regulation of cancer‐induced fat loss.ConclusionsMyeloid cell‐mediated inflammation displays a rather unexpected beneficial function in a murine HCC model. These results demonstrate that immune cells are capable of protecting the host against cancer‐induced tissue wasting, adding a further layer of complexity to the pathogenesis of cachexia and providing a potential explanation for the contradictory results of clinical studies with anti‐inflammatory drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Macrophages protect against loss of adipose tissue during cancer cachexia

Erdem

Möckel

Jumpertz

et al. 2019

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

show abstract

“…For the longest time, the frailty and pronounced muscle weakness that characterizes the majority of HCC patients received much less attention. This has significantly changed in recent years as reports were published from independent groups about the important role of sarcopenia and cachexia in predicting clinical course and response to therapy of HCC patients (4,(34)(35)(36). Cachexia is widely considered to be a multi-factorial syndrome with various manifestations throughout the whole body.…”

Section: Discussionmentioning

confidence: 99%

Macrophages protect against loss of adipose tissue during cancer cachexia

Erdem

Moeckel

Jumpertz

et al. 2018

Preprint

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Cancer cachexia represents a central obstacle in medical oncology as it is associated with poor therapy response and reduced overall survival. Systemic inflammation is considered to be a key driver of cancer cachexia, however, clinical studies with anti-inflammatory drugs failed to show a robust cachexia-inhibiting effect. To address this contradiction, we investigated the functional importance of innate immune cells for hepatocellular carcinoma (HCC)-associated cachexia. To this end, we used a transgenic HCC mouse model intercrossed with mice harboring a defect in myeloid cell-mediated inflammation. We identified robust cachexia in the HCC mouse model as evidenced by a marked loss of visceral fat and lean mass. Computed tomography-based analyses demonstrated that a subgroup of human HCC patients displays reduced visceral fat mass, complementing the murine data. While the myeloid cell-mediated inflammation defect resulted in reduced expression of pro-inflammatory cytokines in the serum of HCC-bearing mice, this unexpectedly did not translate into diminished, but rather enhanced cachexia-associated fat loss. Defective myeloid cell-mediated inflammation was associated with decreased macrophage abundance in visceral adipose tissue, suggesting a role for local macrophages in the regulation of cancer-induced fat loss. Taken together, myeloid cell-mediated inflammation displays a rather unexpected beneficial function in a murine HCC model. These results demonstrate that immune cells are capable of protecting the host against cancer-induced tissue wasting, adding a further layer of complexity to the pathogenesis of cachexia and providing a potential explanation for the contradictory results of clinical studies with anti-inflammatory drugs.

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“…12 Its incidence ranks fifth among all malignant tumors in the world, and its cancer-related mortality ranks third in the world. 13 Surgical hepatectomy and liver transplantation are the main methods to treat HCC. However, the high recurrence rate seriously affects the prognosis and long-term health of HCC patients.…”

Section: Discussionmentioning

confidence: 99%

“…However, the high recurrence rate seriously affects the prognosis and long-term health of HCC patients. 13 Thus, further research on the pathogenesis of HCC is needed to provide new molecular targets for the diagnosis and treatment of HCC. In this study, we found downregulated expression of miR-559 in HCC cell lines, suggesting that miR-559 might be associated with the occurrence of HCC.…”

Section: Discussionmentioning

confidence: 99%

MiR‐559 targets GP73 to suppress proliferation and invasion of hepatocellular carcinoma in vitro

Xiang

Liu

Zhang

et al. 2020

The Kaohsiung J of Med Scie

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Hepatocellular carcinoma (HCC) is one of the common malignant tumors with poor overall prognosis. As a tumor suppressor, the function of miR-559 in HCC is not clear. In this study, quantitative real-time PCR was carried out to measure the expression of miR-559 in HCC cell lines. The effects of miR-559 on HCC cell proliferation, migration, and invasion were evaluated through a series of functional assays. The mechanism through which miR-559 regulates HCC cells was investigated by dualluciferase reporter assay and functional experiments. The results revealed that miR-559 expression was low in HCC cell lines. Upregulation of miR-559 suppressed HCC cell proliferation, migration, and invasion. Dual-luciferase reporter assay confirmed Golgi membrane protein 73 (GP73) as a target gene of miR-559. Moreover, miR-559 could negatively regulate GP73 expression in HCC cells. These results demonstrated that low-level expression of miR-559 was associated with HCC, and overexpression of miR-559 could inhibit HCC cell growth and invasion via targeting GP73.

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Impact of body composition on survival and morbidity after liver resection in hepatocellular carcinoma patients

Cited by 39 publications

References 48 publications

Macrophages protect against loss of adipose tissue during cancer cachexia

Macrophages protect against loss of adipose tissue during cancer cachexia

Macrophages protect against loss of adipose tissue during cancer cachexia

MiR‐559 targets GP73 to suppress proliferation and invasion of hepatocellular carcinoma in vitro

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