Nonsteroidal anti-inflammatory drugs, especially aspirin, are linked to lower risk and better survival of hepatocellular carcinoma: a meta-analysis

Tao, Yuquan; Li, Yesheng; Liu, Xing; Deng, Qing; Yu, Yongchun; Yang, Zongguo

doi:10.2147/cmar.s167560

Cited by 33 publications

(45 citation statements)

References 58 publications

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“…However, a modest reduction of cancer-specific mortality in aspirin users has been widely demonstrated especially for colon cancer but also for breast cancer, hepatocellular carcinoma and other malignant neoplasms. 28,29 Note, MPN was the principal cause of death in 11.8% of patients incurring NPPSC, moreover, infections were a relevant cause of death, which may be partially related to MPN itself. Furthermore, NPPSC do not lead to a dismal survival, therefore, MPN patients with a NPPSC should be cared for carefully with regard to their MPN, and vascular events diligently prevented.…”

Section: Discussionmentioning

confidence: 99%

“…We therefore suggest caution in the use of checkpoint inhibitors concurrently with ruxolitinib in MPN patients developing SC. However, a modest reduction of cancer-specific mortality in aspirin users has been widely demonstrated especially for colon cancer but also for breast cancer, hepatocellular carcinoma and other malignant neoplasms 28,29. However, aspirin was a strongly protective agent in the subset of NPPSC, where cause of death was equally distributed between MPN evolution, SC and other causes.…”

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confidence: 99%

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Second cancers in MPN: Survival analysis from an international study

et al. 2019

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One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A "poor prognosis" SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Second cancers in MPN: Survival analysis from an international study

et al. 2019

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“…Several studies have identified non-resolving chronic inflammation as a key driver of liver fibrosis and HCC progression (48,49). Higher baseline serum levels of inflammatory markers (CRP, IL-6, Cpeptide) are associated with an increased risk of developing HCC in the general population (47) and use of anti-inflammatory drugs are linked to lower risk and better survival in patients with HCC, supporting a role of chronic inflammation in HCC (48)(49)(50). Therefore, we were interested in determining if inflammation plays a role in CLD, which is observed in Sod1KO mice.…”

Section: Discussionmentioning

confidence: 99%

Role of necroptosis in chronic hepatic inflammation and liver disease in Cu/Zn superoxide dismutase deficient mice

Mohammed¹,

Nicklas²,

Thadathil³

et al. 2020

Preprint

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Mice deficient in the antioxidant enzyme Cu/Zn-superoxide dismutase (Sod1-/- or Sod1KO mice) develop spontaneous hepatocellular carcinoma (HCC) with age. Similar to humans, HCC development in Sod1KO mice progresses from fatty liver disease to non-alcoholic steatohepatitis (NASH) with fibrosis, which eventually progresses to HCC. Because liver inflammation is the main mechanism that drives the disease progression in chronic liver disease (CLD) and because necroptosis is a major source of inflammation, we tested the hypothesis that increased necroptosis in the liver plays a role in increased inflammation and progression to fibrosis and HCC in Sod1KO mice. Phosphorylation of MLKL (P-MLKL), a well-accepted marker of necroptosis, and expression of MLKL protein were significantly increased in the livers of Sod1KO mice compared to WT mice indicating increased necroptosis. Similarly, phosphorylation of RIPK3 and RIPK3 protein levels were also significantly increased. Markers of pro-inflammatory M1 macrophages, NLRP3 inflammasome, and transcript levels of pro-inflammatory cytokines and chemokines, e.g., TNFα, IL-6, IL-1β, and Ccl2 that are associated with human NASH and HCC, were significantly increased. Markers of fibrosis and oncogenic transcription factor STAT3 were also upregulated in the livers of Sod1KO mice. Short term treatment of Sod1KO mice with necrostatin-1s (Nec-1s), a necroptosis inhibitor, significantly reduced necroptosis, pro-inflammatory cytokines, fibrosis markers and STAT3 activation. Our data show for the first time that necroptosis-mediated inflammation contributes to fibrosis and HCC progression in Sod1KO mice, a mouse model of accelerated aging and progressive HCC development. These findings suggest that necroptosis might be a target for treating NASH and HCC.

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“…Although there is growing literature concerning the role of NSAIDs in cancer prevention, the results can be contradictory. This is probably due to the poor knowledge of the molecular mechanisms underlying the beneficial or side effects of these drugs in each type of cancer, including HCC [58].…”

Section: Chronic Inflammationmentioning

confidence: 99%

Inflammatory Mechanisms of HCC Development

Refolo

Messa

Guerra

et al. 2020

Cancers

127

105

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HCC (hepatocellular carcinoma) is the second leading cause of cancer deaths worldwide, with several etiologic causes, mostly inflammation-associated. Different inflammatory responses in the liver can be triggered by different etiological agents. The inflammatory process can be resolved or be persistent, depending on the etiology and multiple other factors. Chronic inflammation, tissue remodeling, genetic alterations, and modifications in cellular signaling are considered to be key processes promoting immunosuppression. The progressive immunosuppression leads to the inactivation of anti-tumor immunity involved in HCC carcinogenesis and progression. Tumor cellular processes including DNA damage, necrosis, and ER (endoplasmic reticulum) stress can affect both immune-surveillance and cancer-promoting inflammation, supporting a mutual interdependence. Here, we review the current understanding of how chronic liver injury and inflammation is triggered and sustained, and how inflammation is linked to HCC. The identification of many hepatic microenvironmental inflammatory processes and their effector molecules, has resulted in extensive translational work and promising clinical trials of new immunomodulatory agents.

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Nonsteroidal anti-inflammatory drugs, especially aspirin, are linked to lower risk and better survival of hepatocellular carcinoma: a meta-analysis

Cited by 33 publications

References 58 publications

Second cancers in MPN: Survival analysis from an international study

Second cancers in MPN: Survival analysis from an international study

Role of necroptosis in chronic hepatic inflammation and liver disease in Cu/Zn superoxide dismutase deficient mice

Inflammatory Mechanisms of HCC Development

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