Tumor necrosis factor-like weak inducer of apoptosis and its potential roles in lupus nephritis

Liu, Zhichun; Zhou, Qiaoling

doi:10.1007/s00011-011-0420-8

Cited by 16 publications

(15 citation statements)

References 63 publications

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“…Here, we show these effects in tumor cell lines and that a TWEAK blockade with an anti-TWEAK mAb, RG7212, results in significant tumor growth inhibition (TGI) in multiple tumor models expressing Fn14. These in vitro and in vivo data are consistent with tumor-promoting effects shown with other TNF family receptors lacking death domains (19,20) and with TWEAK data in disease models in animals and pathologic conditions in humans (21,22).…”

Section: Introductionsupporting

confidence: 86%

“…In contrast to data showing TWEAK proinflammatory, proangiogenic, and proliferation-inducing effects in disease models in animals (5,(23)(24)(25) and association of pathway activation with human disease (21,22,(26)(27)(28), some published in vitro studies have shown that TWEAK induces apoptosis via upregulation of TNFa (29) or in combination with IFNg in a small number of tumor cell lines (8). In the absence of IFNg, apoptosis induction was modest (30) or required relatively high TWEAK concentrations (29).…”

Section: Introductionmentioning

confidence: 94%

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RG7212 Anti-TWEAK mAb Inhibits Tumor Growth through Inhibition of Tumor Cell Proliferation and Survival Signaling and by Enhancing the Host Antitumor Immune Response

Yin

Luistro

Zhong

et al. 2013

Clinical Cancer Research

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Purpose: To explore the role of TWEAK in tumor growth and antitumor immune response and the activity and mechanism of RG7212, an antagonistic anti-TWEAK antibody, in tumor models.Experimental Design: TWEAK-induced signaling and gene expression were explored in tumor cell lines and inhibition of these effects and antitumor efficacy with RG7212 treatment was assessed in human tumor xenograft-, patient-derived xenograft, and syngeneic tumor models and phase I patients. Genetic features correlated with antitumor activity were characterized.Results: In tumor cell lines, TWEAK induces proliferation, survival, and NF-kB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. TWEAK-inducible CD274, CCL2, CXCL-10 and -11 modulate T-cell and monocyte recruitment, T-cell activation, and macrophage differentiation. These factors and TWEAK-induced signaling were decreased, and tumor, blood, and spleen immune cell composition was altered with RG7212 treatment in mice. RG7212 inhibits tumor growth in vivo in models with TWEAK receptor, Fn14, expression, and markers of pathway activation. In phase I testing, signs of tumor shrinkage and stable disease were observed without dose-limiting toxicity. In a patient with advanced, Fn14-positive, malignant melanoma with evidence of tumor regression, proliferation markers were dramatically reduced, tumor T-cell infiltration increased, and tumor macrophage content decreased. Antitumor activity, a lack of toxicity in humans and animals and no evidence of antagonism with standard of care or targeted agents in mice, suggests that RG7212 is a promising agent for use in combination therapies in patients with Fn14-positive tumors.

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Section: Introductionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 94%

RG7212 Anti-TWEAK mAb Inhibits Tumor Growth through Inhibition of Tumor Cell Proliferation and Survival Signaling and by Enhancing the Host Antitumor Immune Response

Yin

Luistro

Zhong

et al. 2013

Clinical Cancer Research

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“…Interestingly, it has been reported that a short course of anti-tumor necrosis factor therapy with infliximab had a prolonged beneficial effect on proteinuria in LN (5). More recently, other proinflammatory molecules, such as TWEAK, have emerged as promising targets in LN (6). Hopefully, clinical trials with such targets will deliver the clinical outcomes we need.…”

Section: To the Editormentioning

confidence: 99%

Antiinflammatory strategies, not just B cell depletion, are required for optimal therapy for severe proliferative lupus nephritis: Comment on the article by Rovin et al

Kirou¹,

Gkrouzman²,

Chevalier³

et al. 2012

Arthritis & Rheumatism

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“…LN is a common and serious complication of systemic lupus erythematosus patients, and is considered to be the crucial factor in the prognosis of the disease (Liu and Zhou, 2012). Immune cells, cytokines, and epigenetic factors have all been recently implicated in LN pathogenesis (Schwartz et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Decreased TIM-3 mRNA expression in peripheral blood mononuclear cells from nephropathy patients

Cai¹,

Liu²,

Qiao³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Increasing evidence shows that TIM-1 and TIM-3 influence chronic autoimmune diseases, and their expression levels in immune cells from nephritic patients are still unknown. Real-time transcription-polymerase chain reaction analysis was used to determine expression levels of TIM-1 and TIM-3 mRNA in peripheral blood mononuclear cells (PBMCs) from 36 patients with minimal change glomerulopathy (MCG), 65 patients with lupus nephritis (LN), 78 patients with IgA nephropathy (IgAN), 55 patients with membranous nephropathy (MN), 22 patients with crescentic glomerulonephritis (CGN), 26 patients with anaphylactoid purpura nephritis (APN), and 63 healthy controls. TIM-3 mRNA expression significantly decreased in PBMCs from nephritic patients (LN, P < 0.0001; MCG, P < 0.0001; MN, P = 0.0031; CGN, P = 0.0464; IgAN, P = 0.0002; APN, P = 0.0392) compared with healthy controls. In contrast, there was no significant difference in TIM-1 mRNA expression between the patients and the healthy X.Z. Cai et al. 6544©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 6543-6548 (2015) controls. Our results suggest that insufficient expression of TIM-3 mRNA may be involved in the pathogenesis of nephropathy.

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Tumor necrosis factor-like weak inducer of apoptosis and its potential roles in lupus nephritis

Cited by 16 publications

References 63 publications

RG7212 Anti-TWEAK mAb Inhibits Tumor Growth through Inhibition of Tumor Cell Proliferation and Survival Signaling and by Enhancing the Host Antitumor Immune Response

RG7212 Anti-TWEAK mAb Inhibits Tumor Growth through Inhibition of Tumor Cell Proliferation and Survival Signaling and by Enhancing the Host Antitumor Immune Response

Antiinflammatory strategies, not just B cell depletion, are required for optimal therapy for severe proliferative lupus nephritis: Comment on the article by Rovin et al

Decreased TIM-3 mRNA expression in peripheral blood mononuclear cells from nephropathy patients

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