Preclinical Models for Studying NASH-Driven HCC: How Useful Are They?

Cell Metabolism, Journal Year: 2018, Volume and Issue: 29(1), P. 18 - 26

Published: Nov. 15, 2018

Language: Английский

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The microbiota and microbiome in pancreatic cancer: more influential than expected

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: May 20, 2019

Microbiota is just beginning to be recognized as an important player in carcinogenesis and the interplay among microbes greater than expected. Pancreatic ductal adenocarcinoma (PDAC) a highly lethal disease for which mortality closely parallels incidence. Early detection would provide best opportunity increase survival rates. Specific well-studied oral, gastrointestinal, intrapancreatic some kinds of hepatotropic viruses bactibilia may have potential etiological roles pancreatic carcinogenesis, or modulating individual responses oncotherapy. Concrete mechanisms mainly involve perpetuating inflammation, regulating immune system-microbe-tumor axis, affecting metabolism, altering tumor microenvironment. The revolutionary technology omics has generated insight into cancer microbiomes. A better understanding microbiota PDAC might lead establishment screening early-stage diagnosis methods, implementation bacteriotherapy, adjustment therapeutic efficacy even alleviating adverse effects, creating new opportunities fostering hope desperate patients.

Language: Английский

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Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome

Signal Transduction and Targeted Therapy, Journal Year: 2019, Volume and Issue: 4(1)

Published: Oct. 11, 2019

Abstract The trillions of microorganisms in the gut microbiome have attracted much attention recently owing to their sophisticated and widespread impacts on numerous aspects host pathophysiology. Remarkable progress large-scale sequencing mass spectrometry has increased our understanding influence and/or its metabolites onset progression extraintestinal cancers efficacy cancer immunotherapy. Given plasticity microbial composition function, microbial-based therapeutic interventions, including dietary modulation, prebiotics, probiotics, as well fecal transplantation, potentially permit development novel strategies for therapy improve clinical outcomes. Herein, we summarize latest evidence involvement immunity metabolism, effects immune response, modulate microbiome, discuss ongoing studies future areas research that deserve focused efforts.

Language: Английский

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Gut microbiome and cancer immunotherapy

Cancer Letters, Journal Year: 2019, Volume and Issue: 447, P. 41 - 47

Published: Jan. 24, 2019

Microbiome is becoming crucial in that the balance between human health and disease can be mediated by gut microbiome. The microbiome modulate host immune system both locally systemically. Cancer immunotherapy has emerged as a promising way treatment of patients with cancer. Accumulating evidence supports affects therapeutic efficacy cancer immunotherapy, particularly checkpoint inhibitors. Here, we discuss mutual relationship among microbiome, cancer, immunity, focus on immunotherapy. Also, briefly introduce relevant challenges affect present possible solutions. • plays key role disease, immunity Gut especially ICIs involving blockade PD-1 or PD-L1 CTLA-4. Despite potential some remain, including selection an optimal FMT donor.

Language: Английский

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Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease

Free Radical Biology and Medicine, Journal Year: 2019, Volume and Issue: 144, P. 293 - 309

Published: May 29, 2019

Language: Английский

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Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers

Journal for ImmunoTherapy of Cancer, Journal Year: 2021, Volume and Issue: 9(12), P. e003334 - e003334

Published: Dec. 1, 2021

The gut microbiome is associated with the response to immunotherapy for different cancers. However, impact of on hepatobiliary cancers receiving remains unknown. This study aims investigate relationship between and clinical anti-programmed cell death protein 1 (PD-1) in patients advanced cancers.Patients unresectable hepatocellular carcinoma or biliary tract who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples collected before during anti-PD-1 treatment analyzed metagenomic sequencing. Significantly differentially enriched taxa prognosis identified. Kyoto Encyclopedia Genes Genomes database MetaCyc further applied annotate explore potential mechanism influencing cancer immunotherapy.In total, 65 included this study. Seventy-four significantly benefit (CBR) group 40 non-clinical (NCB) group. Among these taxa, higher abundance Lachnospiraceae bacterium-GAM79 Alistipes sp Marseille-P5997, which CBR group, achieved longer progression-free survival (PFS) overall (OS) than lower abundance. Higher Ruminococcus calidus Erysipelotichaceae bacterium-GAM147 was also observed better PFS. In contrast, worse PFS OS found Veillonellaceae, NCB Functional annotation indicated that energy metabolism while amino acid metabolism, may modulate addition, immunotherapy-related adverse events affected by diversity relative abundance.We demonstrate Taxonomic signatures responders are effective biomarkers predict immunotherapy, might provide a new therapeutic target immunotherapy.

Language: Английский

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Gut Microbiome Directs Hepatocytes to Recruit MDSCs and Promote Cholangiocarcinoma

Cancer Discovery, Journal Year: 2020, Volume and Issue: 11(5), P. 1248 - 1267

Published: Dec. 15, 2020

Gut dysbiosis is commonly observed in patients with cirrhosis and chronic gastrointestinal disorders; however, its effect on antitumor immunity the liver largely unknown. Here we studied how gut microbiome affects cholangiocarcinoma. Primary sclerosing cholangitis (PSC) or colitis, two known risk factors for cholangiocarcinoma which promote tumor development mice, caused an accumulation of CXCR2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). A decrease barrier function mice PSC colitis allowed gut-derived bacteria lipopolysaccharide to appear induced CXCL1 expression hepatocytes through a TLR4-dependent mechanism PMN-MDSCs. In contrast, neomycin treatment blocked PMN-MDSC inhibited growth even absence disease colitis. Our study demonstrates that controls form immunosuppressive environment by increasing PMN-MDSCs cancer. SIGNIFICANCE: MDSCs have been shown be tumors suppress immunity. show can control context benign colitis.See related commentary Chagani Kwong, p. 1014.This article highlighted This Issue feature, 995.

Language: Английский

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Cancer pharmacomicrobiomics: targeting microbiota to optimise cancer therapy outcomes

Gut, Journal Year: 2022, Volume and Issue: 71(7), P. 1412 - 1425

Published: March 11, 2022

Despite the promising advances in novel cancer therapy such as immune checkpoint inhibitors (ICIs), limitations including therapeutic resistance and toxicity remain. In recent years, relationship between gut microbiota has been extensively studied. Accumulating evidence reveals role of defining efficacy toxicity. Unlike host genetics, can be easily modified via multiple strategies, faecal transplantation (FMT), probiotics antibiotics. Preclinical studies have identified mechanisms on how microbes influence treatment outcomes. Clinical trials also demonstrated potential modulation treatments. Herein, we review mechanistic insights microbial interactions with chemotherapy ICIs, particularly focusing interplay bacteria pharmacokinetics (eg, metabolism, enzymatic degradation) or pharmacodynamics immunomodulation) treatment. The translational basic findings clinical settings is then explored, using predictive biomarkers by antibiotics, probiotics, prebiotics, dietary modulations FMT. We further discuss current patients suggest essential directions for future study. era personalised medicine, it crucial to understand its cancer. Manipulating augment responses provide new into

Language: Английский

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Alteration in gut microbiota associated with hepatitis B and non-hepatitis virus related hepatocellular carcinoma

Gut Pathogens, Journal Year: 2019, Volume and Issue: 11(1)

Published: Jan. 18, 2019

The onset of hepatocellular carcinoma (HCC) ranked fifth malignancies all over the world. Increasing evidences showed that distribution HCC was related to incidence chronic hepatitis B virus (HBV) infection and other factors, such as alcoholism, aflatoxin B1 ingestion obesity. Recent studies demonstrated gut dysbiosis plays an important role in liver diseases. However, researches on microbiota HBV non-HBV non-HCV have not been reported. In this study, we investigated differences between (B-HCC) (NBNC-HCC), finally found some potential bacteria, linking different pathological mechanism both types HCCs. We carried out 16S rRNA analyses a cohort 33 healthy controls, 35 individuals with 22 (NBNC) (NBNC-HCC). species richness fecal B-HCC patients much higher than two groups. Interestingly, feces NBNC-HCC harbored more pro-inflammatory bacteria (Escherichia-Shigella, Enterococcus) reduced levels Faecalibacterium, Ruminococcus, Ruminoclostridium which results decrease anti-inflammatory short-chain fatty acids. had relatively fewer abundance multiple biological pathways amino acid glucose metabolism, but high level transport secretion types. opposite bacterial composition associated versus patients. Meanwhile, aberrant network occurred differently Our study indicated differential involved functions or pathways. suggested modification specific may provide therapeutic benefit for NBNC-HCC.

Language: Английский

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Incidence of Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review, Meta-analysis, and Meta-regression

Clinical Gastroenterology and Hepatology, Journal Year: 2021, Volume and Issue: 20(2), P. 283 - 292.e10

Published: May 28, 2021

Background & AimsNonalcoholic fatty liver disease (NAFLD) may be a risk factor for hepatocellular carcinoma (HCC), but the extent of this association still needs to addressed. Pooled incidence rates HCC across spectrum NAFLD have never been estimated by meta-analysis.MethodsIn systematic review, we searched Web Science, Embase, PubMed, and Cochrane Library from January 1, 1950 through July 30, 2020. We included studies reporting on in patients with NAFLD. The main outcomes were pooled incidences at distinct severity stages. Summary estimates calculated random-effects models. Sensitivity analyses meta-regression carried out address heterogeneity.ResultsWe 18 involving 470,404 patients. In stage earlier than cirrhosis, rate was 0.03 per 100 person-years (95% confidence interval [CI], 0.01–0.07; I2 = 98%). 3.78 CI, 2.47–5.78; 93%). Patients cirrhosis undergoing regular screening had an 4.62 2.77–7.72; 77%).ConclusionsPatients NAFLD-related developing similar that reported other etiologies. Evidence documenting nonalcoholic steatohepatitis or simple steatosis is limited, these populations lie below thresholds used recommend screening. Well-designed prospective subpopulations are needed. protocol review registered Prospero database (registration number CRD42018092861). Nonalcoholic meta-analysis. heterogeneity. 77%).

Language: Английский

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