TNF-α-mediated NF-κB survival signaling impairment by cisplatin enhances JNK activation allowing synergistic apoptosis of renal proximal tubular cells

Benedetti, Giulia; Fredriksson, Lisa; Herpers, Bram; Meerman, John H.N.; Water, Bob van de; Graauw, Marjo de

doi:10.1016/j.bcp.2012.10.012

Cited by 73 publications

(58 citation statements)

References 58 publications

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“…A molecule strongly associated with cisplatin-induced (nephro-) toxicity is TNFa (28,(31)(32)(33). Although this cytokine has been proposed as a strong trigger of cancer cell death (34), its life-threatening toxicity when administered systemically prohibits systemic clinical use (31,35).…”

Section: Discussionmentioning

confidence: 99%

“…These data show that the introduction of different forms of active T cell-based immunotherapies into clinical practice calls for detailed analyses of the different forms of chemotherapy that best synergize with and support the immunotherapy. What is a scourge in the toxicity of cisplatin toward kidney tubular epithelial cells (28,36) turns out to be a blessing in the enhanced demise of tumor cells helped along by the locally high levels of TNFa produced by vaccine-induced tumorspecific T cells. Other investigators have shown marked differences in the induction of immunogenic cell death by different chemotherapeutic compounds (47).…”

Section: Discussionmentioning

confidence: 99%

“…leading to a shift in apoptotic programming and, causing tubular cell apoptosis at much lower cisplatin levels than in the absence of TNFa (28). We hypothesized that a similar mechanism may play a role in the synergy between vaccine-induced T-cell responses and cisplatin treatment.…”

Section: Combined Treatment Of Vaccination With Cisplatin Decreases Tmentioning

confidence: 99%

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Vaccine-Induced Tumor Necrosis Factor–Producing T Cells Synergize with Cisplatin to Promote Tumor Cell Death

Sluis

Duikeren

Huppelschoten

et al. 2015

Clinical Cancer Research

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Purpose: Cancer immunotherapy, such as vaccination, is an increasingly successful treatment modality, but its interaction with chemotherapy remains largely undefined. Therefore, we explored the mechanism of synergy between vaccination with synthetic long peptides (SLP) of human papillomavirus type 16 (HPV16) and cisplatin in a preclinical tumor model for HPV16.Experimental Design: SLP vaccination in this preclinical tumor model allowed the elucidation of novel mechanisms of synergy between chemo-and immunotherapy. By analyzing the tumor immune infiltrate, we focused on the local intratumoral effects of chemotherapy, vaccination, or the combination.Results: Of several chemotherapeutic agents, cisplatin synergized best with SLP vaccination in tumor eradication, without requirement for the maximum-tolerated dose (MTD). Upon SLP vaccination, tumors were highly infiltrated with HPV-specific, tumor necrosis factor-a (TNFa)-and interferon-g (IFNg)-producing T cells. Upon combined treatment, tumor cell proliferation was significantly decreased compared with single treated and untreated tumors. Furthermore, we showed that TNFa strongly enhanced cisplatin-induced apoptotic tumor cell death in a JNKdependent manner. This is consistent with upregulation of proapoptotic molecules and with enhanced cell death in vivo upon combined SLP vaccination and cisplatin treatment. In vivo neutralization of TNFa significantly reduced the antitumor responses induced by the combined treatment.Conclusion: Taken together, our data show that peptide vaccination with cisplatin treatment leads to decreased tumor cell proliferation and TNFa-induced enhanced cisplatin-mediated killing of tumor cells, together resulting in superior tumor eradication.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Vaccine-Induced Tumor Necrosis Factor–Producing T Cells Synergize with Cisplatin to Promote Tumor Cell Death

Sluis

Duikeren

Huppelschoten

et al. 2015

Clinical Cancer Research

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“…Cisplatin activates many signaling pathways that are inhibited by triptolide. Cisplatin causes increased nuclear factor kB binding activity leading to prolonged JNK phosphorylation (Ramesh and Reeves, 2005;Benedetti et al, 2013). In HK cells, cisplatin increases the expression of p-ERK1/2 and p38 MAPK (Park et al, 2012a).…”

Section: Discussionmentioning

confidence: 99%

The Water-Soluble Triptolide Derivative PG490-88 Protects against Cisplatin-Induced Acute Kidney Injury

Kim

Ravichandran

Özkök

et al. 2014

J Pharmacol Exp Ther

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Triptolide, a traditional Chinese medicine, has anti-inflammatory, antiproliferative, and proapoptotic properties. As interstitial inflammation and tubular apoptosis are features of cisplatin-induced acute kidney injury (AKI), we determined the effect of the watersoluble triptolide derivative 14-succinyl triptolide sodium salt (PG490-88) in a mouse model of cisplatin-induced AKI. PG490-88 resulted in a significant decrease in blood urea nitrogen (BUN), serum creatinine, and acute tubular necrosis (ATN) score, and a nonsignificant increase in tubular apoptosis score in AKI. The mitogen-activated protein kinase (MAPK) pathway is activated in AKI. On immunoblot analysis, phosphoextracellular signal-regulated kinase (p-ERK) was increased 3.6-fold in AKI and 2.0-fold inhibited by PG490-88. Phospho-c-Jun N-terminal kinase (p-JNK) was increased in AKI. PG490-88 resulted in a nonsignificant decrease in p-JNK. Phospho-p38 was not affected by cisplatin or PG490-88. MAPK phosphatase-1 (MKP-1) that negatively regulates MAPK signaling has not previously been studied in AKI. MKP-1 activity was not affected by cisplatin or PG490-88. Changes in p-ERK, p-JNK, and MKP-1 were confirmed on reverse protein phase analysis. The ERK inhibitor U0126 resulted in lower BUN and serum creatinine, suggesting a mechanistic role of ERK in AKI. The increase in interleukin-1a (IL-1a), IL-1b, IL-6, CXCL1, and IL-33 in the kidney in AKI was unaffected by PG490-88. In summary, PG490-88 protects against AKI and ATN despite no decrease in tubular apoptosis. The protection of PG490-88 against AKI was associated with a decrease in p-ERK and was independent of MKP-1 and proinflammatory cytokines. In conclusion, PG490-88 protects against cisplatin-induced AKI possibly by decreasing p-ERK.

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“…the algorithms can be used to discriminate specific target elements in the images such as cells, organelles, biological structures and processes. these target elements can be traced to define the exact size, shape and volume of biological structures (e.g., vasculature, neurites, microtubules) or tracked over time to show dynamic movements of biological processes (e.g., cell migration, differentiation, tions to screen targets and MoA of compounds (Krausz, 2007;Verissimo et al, 2012;Benedetti et al, 2013). Within the field of HCI, there are many different assay designs that make use of the various biological systems, probes and imaging technologies that are currently available.…”

Section: Current High Content Imaging Applications In Safety Sciencesmentioning

confidence: 99%

Current approaches and future role of high content imaging in safety sciences and drug discovery

Vliet

Daneshian

Beilmann

et al. 2014

ALTEX

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* a report of t 4 -the transatlantic think tank for toxicology, a collaboration of the toxicologically oriented chairs in Baltimore, Konstanz and Utrecht sponsored by the Doerenkamp-Zbinden Foundation; participants do not represent their institutions and do not necessarily endorse all recommendations made.Disclaimer: This document has been reviewed by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. Summary High content imaging combines automated microscopy with image analysis approaches to simultaneously quantify multiple phenotypic and/or functional parameters in biological systems. The technology has become an important tool in the fields of safety sciences and drug discovery, because it can be used for mode-of-action identification, determination of hazard potency and the discovery of toxicity targets and biomarkers. In contrast to conventional biochemical endpoints, high content imaging provides insight into the spatial distribution and dynamics of responses in biological systems

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TNF-α-mediated NF-κB survival signaling impairment by cisplatin enhances JNK activation allowing synergistic apoptosis of renal proximal tubular cells

Cited by 73 publications

References 58 publications

Vaccine-Induced Tumor Necrosis Factor–Producing T Cells Synergize with Cisplatin to Promote Tumor Cell Death

Vaccine-Induced Tumor Necrosis Factor–Producing T Cells Synergize with Cisplatin to Promote Tumor Cell Death

The Water-Soluble Triptolide Derivative PG490-88 Protects against Cisplatin-Induced Acute Kidney Injury

Current approaches and future role of high content imaging in safety sciences and drug discovery

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