Gene- and exon-expression profiling reveals an extensive LPS-induced response in immune cells in patients with cirrhosis

Gandoura, Sonia; Weiss, Emmanuel; Rautou, Pierre‐Emmanuel; Fasseu, Magali; Gustot, Thierry; Lemoine, Frédéric; Hurtado-Nédelec, Margarita; Hego, Caroline; Vadrot, Nathalie; Elkrief, Laure; Lettéron, Philippe; Tellier, Z.; Pocidalo, Marie-Anne; Valla, Dominique; Lebrec, Didier; Groyer, André; Monteiro, Renato C.; Grange, Pierre de la; Moreau, Richard

doi:10.1016/j.jhep.2012.12.025

Cited by 71 publications

(66 citation statements)

References 46 publications

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“…Arrays were normalized according to the GC-RMA normalization procedure (14). Analyses of array datasets were made using EASANA (GenoSplice technology), normalization, background corrections, and gene annotations were performed as previously described (15). Only genes expressed in at least one compared condition were analyzed.…”

Section: Mutation Screeningmentioning

confidence: 99%

Acquired Resistance to Endocrine Treatments Is Associated with Tumor-Specific Molecular Changes in Patient-Derived Luminal Breast Cancer Xenografts

Cottu¹,

Bièche

Assayag³

et al. 2014

Clinical Cancer Research

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Purpose: Patients with luminal breast cancer (LBC) often become endocrine resistant over time. We investigated the molecular changes associated with acquired hormonoresistances in patient-derived xenografts of LBC. Experimental Design: Two LBC xenografts (HBCx22 and HBCx34) were treated with different endocrine treatments (ET) to obtain xenografts with acquired resistances to tamoxifen (TamR) and ovariectomy (OvaR). PI3K pathway activation was analyzed by Western blot analysis and IHC and responses to ET combined to everolimus were investigated in vivo. Gene expression analyses were performed by RT-PCR and Affymetrix arrays. Results: HBCx22 TamR xenograft was cross-resistant to several hormonotherapies, whereas HBCx22 OvaR and HBCx34 TamR exhibited a treatment-specific resistance profile. PI3K pathway was similarly activated in parental and resistant xenografts but the addition of everolimus did not restore the response to tamoxifen in TamR xenografts. In contrast, the combination of fulvestrant and everolimus induced tumor regression in vivo in HBCx34 TamR, where we found a cross-talk between the estrogen receptor (ER) and PI3K pathways. Expression of several ER-controlled genes and ER coregulators was significantly changed in both TamR and OvaR tumors, indicating impaired ER transcriptional activity. Expression changes associated with hormonoresistance were both tumor and treatment specific and were enriched for genes involved in cell growth, cell death, and cell survival. Conclusions: PDX models of LBC with acquired resistance to endocrine therapies show a great diversity of resistance phenotype, associated with specific deregulations of ER-mediated gene transcription. These models offer a tool for developing anticancer therapies and to investigate the dynamics of resistance emerging during pharmacologic interventions. Clin Cancer Res; 20(16); 4314–25. ©2014 AACR.

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Section: Mutation Screeningmentioning

confidence: 99%

Acquired Resistance to Endocrine Treatments Is Associated with Tumor-Specific Molecular Changes in Patient-Derived Luminal Breast Cancer Xenografts

Cottu¹,

Bièche

Assayag³

et al. 2014

Clinical Cancer Research

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“…The engagement of PRRs stimulates intracellular signaling cascades that activate transcription factors, such as NF-κB and AP-1, among others [3,4]. These transcription factors induce a battery of genes, including those coding for inflammatory cytokines and chemokines [5,6]. This inflammatory response plays a major role in host resistance to infection, i.e.…”

Section: Mechanisms Of Infection-related Aclfmentioning

confidence: 99%

“…Following a challenge with lipopolysaccharide (LPS, a PAMP recognized by TLR4; table 1), LPS-induced plasma TNF-α levels are significantly higher in cirrhotic than in noncirrhotic animals [11,12,13]. In monocytes or peripheral blood mononuclear cells (PBMCs), the ex vivo LPS-stimulated production of proinflammatory molecules is more marked in cells from patients with cirrhosis than in cells from healthy subjects [6,14,15,16,17,18,19]. Previous studies have shown that the mechanisms involved in negative feedback control of TLR4 signaling are defective in monocytes from patients with cirrhosis.…”

Section: Mechanisms Of Infection-related Aclfmentioning

confidence: 99%

“…Among patients with spontaneous bacterial peritonitis, those with high levels of proinflammatory cytokines in the plasma and ascitic fluid are at risk of developing acute kidney injury (a form of ACLF) [20]. Another study has shown that the higher the LPS induction of inflammatory genes, the higher the risk of short-term death [6]. ACLF is the main cause of death in patients with cirrhosis [1].…”

Section: Mechanisms Of Infection-related Aclfmentioning

confidence: 99%

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Role of Infections in Acute-on-Chronic Liver Failure

Moreau¹

2015

Dig Dis

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Patients with cirrhosis are prone to developing bacterial infections. Moreover, bacterial infection is the most common identifiable trigger of acute-on-chronic liver failure (ACLF), which is characterized by organ failures and a high risk of death. There is evidence of an excessive immune response of the host as a major mechanism leading to the development of organ failures in patients with cirrhosis. However, a role for direct tissue damage caused by bacterial toxins and virulence factors cannot be excluded. Failed tolerance mechanisms may also contribute to organ failures, although the involved mechanisms are unclear. A proportion of patients with infection-related ACLF have a prolonged stay in the intensive care unit. These patients have immune suppression, increased risk of superinfection and poor outcome. Immune suppression might be a consequence of the first infection episode that has led patients to be admitted to hospital.

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“…A first hypothesis is that ''persistent'' infection may elicit an excessive immune response of the host resulting in cytokine storm and subsequent tissue damage [1]. There is some evidence that some patients with cirrhosis have an excessive proinflammatory response of innate immune cells to bacterial components [18][19][20].…”

mentioning

confidence: 99%

Gene- and exon-expression profiling reveals an extensive LPS-induced response in immune cells in patients with cirrhosis

Cited by 71 publications

References 46 publications

Acquired Resistance to Endocrine Treatments Is Associated with Tumor-Specific Molecular Changes in Patient-Derived Luminal Breast Cancer Xenografts

Acquired Resistance to Endocrine Treatments Is Associated with Tumor-Specific Molecular Changes in Patient-Derived Luminal Breast Cancer Xenografts

Role of Infections in Acute-on-Chronic Liver Failure

The burden of extended-spectrum β-lactamase-producing Enterobacteriaceae in patients with cirrhosis

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