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            Generation by bacillus Calmette-Guérin Induces the Cellular Oxidative Stress Response Required for bacillus Calmette-Guérin Direct Effects on Urothelial Carcinoma Biology

Shah, Gopitkumar; Zielonka, Jacek; Chen, Fanghong; Zhang, Guangjian; Cao, Yanli; Kalyanaraman, Balaraman; See, William A.

doi:10.1016/j.juro.2014.05.115

Cited by 19 publications

(13 citation statements)

References 30 publications

(32 reference statements)

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“…Consistently, we observed a dramatically higher sensitivity to H 2 O 2 -induced cell damage of MCR sTn in comparison with MCR Nc . This is of particular interest if one considers that the generation of reactive oxygen species by BCG is a crucial mechanism of BCG-induced damage to BC cells [ 4 ]. Thus, it is possible that an increased sensitivity to oxidizing agents by sTn-expressing bladder cancers is one of the basis of their better response to BCG therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Although the precise mechanisms of its action remains uncertain, it is clear that BCG is internalized by cancer cells and induces a local inflammatory response, which is responsible for the anti-tumor effect [ 1 – 3 ]. Moreover, oxidizing agents released by BCG play a key role in the killing of BC cells [ 4 ]. A comprehensive understanding of how BCG modulates the immune system and induces phenotypic changes of BC could greatly improve patient's treatment.…”

Section: Introductionmentioning

confidence: 99%

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Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage

et al. 2017

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The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. A poorly understood correlation between the expression of sTn and BC patient's response to BCG was previously observed. By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders. To investigate the role of sTn in BC cell biology and BCG response, we established the cell lines MCRsTn and MCRNc by retroviral transduction of the BC cell line MCR with the ST6GALNAC1 cDNA or with an empty vector, respectively. Compared with MCRNc, BCG-stimulated MCRsTn secreted higher levels of IL-6 and IL-8 and their secretome induced a stronger IL-6, IL-1β, and TNFα secretion by macrophages, suggesting the induction of a stronger inflammatory response. Transcriptomic analysis of MCRNc and MCRsTn revealed that ST6GALNAC1/sTn expression modulates hundreds of genes towards a putative more malignant phenotype and down-regulates several genes maintaining genomic stability. Consistently, MCRsTn cells displayed higher H2O2 sensitivity. In MCRsTn,, BCG challenge induced an increased expression of several regulatory non coding RNA genes. These results indicate that the expression of ST6GALNAC1/sTn improves the response to BCG therapy by inducing a stronger macrophage response and alters gene expression towards malignancy and genomic instability, increasing the sensitivity of BC cells to the oxidizing agents released by BCG.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage

et al. 2017

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“…Therefore, this study was not only designed to investigate whether serum IGF-1 levels could predict the severity and prognosis in patients with sepsis, but we also tried to determine the association between IGF-1 and miRNA-1 in patients. H 2 O 2 has previously been proven to induce oxidative injury in cells (11,12); therefore, …”

Section: Introductionmentioning

confidence: 99%

IGF-1 may predict the severity and outcome of patients with sepsis and be associated with microRNA-1 level changes

Zhang

Liu

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. IGF-1 functions as an anti-oxidative stress molecule and some critical patients with sepsis have a lower level of serum IGF-1. However, the association between IGF-1 and the severity or prognosis of sepsis remains unclear. This study aimed to elucidate the relationship between serum IGF-1 levels and the severity and prognosis of sepsis, and the possible mechanism was analyzed. Clinical characteristics of patients with sepsis were recorded and analyzed. Serum IGF-1 levels and micro (mi)RNA-1 levels were tested using radioimmunoassay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, respectively. The A549 cell line and HKC cell line were cultured in vitro and exposed to H 2 O 2 with or without IGF-1 treatment. Cell death was detected by analyzing cell death markers via ELISA kits, and miRNA-1 levels were detected after H 2 O 2 exposure using RT-qPCR analysis. miRNA-1 in cells was upregulated by transfection and IGF-1 mRNA was detected to determine its relationship with miRNA-1. Once again, cell ELISA kits were used to analyze cell death markers after transfection. Serum IGF-1 levels were reduced in patients with sepsis, whereas miRNA-1 levels were higher (P<0.05 vs. healthy control). Patients in the septic shock subgroup or dead patients had the lowest IGF-1 levels and the highest miRNA-1 levels (P<0.05 vs. sepsis and severe sepsis). IGF-1 levels were inversely proportional to the miRNA-1 level. In vitro, IGF-1 reduced the cell death caused by H 2 O 2 . miRNA-1 transfection effectively increased the sensitivity of cells to H 2 O 2 damage by reducing the expression of IGF-1, which was able to prevent cells from injury caused by H 2 O 2 . The transfection of negative control miRNA did not influence the level of IGF-1 miRNA and the sensitivity to H 2 O 2 damage. In conclusion, low IGF-1 levels in patients with sepsis may predict increased severity of the condition and poor prognosis. The possible mechanism is that the excessive miRNA-1 levels reduce IGF-1 levels, resulting in insufficient anti-oxidative action by IGF-1 which increases the injury caused by oxidative stress in patients with sepsis.

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“…These are all aimed at improving anti-tumor immune responses. BCG elicits production of hydrogen peroxide, superoxide, and free radical oxygen, promoting oxidative stress within urothelial carcinoma cells [ 139 ]. Oxidative stress promotes DNA damage and lipid peroxidation, which leads to tumor cell death and release of the “danger signal” HMGB1 (high-mobility group protein 1) that stimulates the innate immune response [ 140 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Hsp90 in urothelial carcinoma

et al. 2015

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Urothelial carcinoma, or transitional cell carcinoma, is the most common urologic malignancy that carries significant morbidity, mortality, recurrence risk and associated health care costs. Despite use of current chemotherapies and immunotherapies, long-term remission in patients with muscle-invasive or metastatic disease remains low, and disease recurrence is common. The molecular chaperone Heat Shock Protein-90 (Hsp90) may offer an ideal treatment target, as it is a critical signaling hub in urothelial carcinoma pathogenesis and potentiates chemoradiation. Preclinical testing with Hsp90 inhibitors has demonstrated reduced proliferation, enhanced apoptosis and synergism with chemotherapies and radiation. Despite promising preclinical data, clinical trials utilizing Hsp90 inhibitors for other malignancies had modest efficacy. Therefore, we propose that Hsp90 inhibition would best serve as an adjuvant treatment in advanced muscle-invasive or metastatic bladder cancers to potentiate other therapies. An overview of bladder cancer biology, current treatments, molecular targeted therapies, and the role for Hsp90 inhibitors in the treatment of urothelial carcinoma is the focus of this review.

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H ₂ O ₂ Generation by bacillus Calmette-Guérin Induces the Cellular Oxidative Stress Response Required for bacillus Calmette-Guérin Direct Effects on Urothelial Carcinoma Biology

Cited by 19 publications

References 30 publications

Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage

Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage

IGF-1 may predict the severity and outcome of patients with sepsis and be associated with microRNA-1 level changes

Targeting Hsp90 in urothelial carcinoma

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H 2 O 2 Generation by bacillus Calmette-Guérin Induces the Cellular Oxidative Stress Response Required for bacillus Calmette-Guérin Direct Effects on Urothelial Carcinoma Biology

Cited by 19 publications

References 30 publications

Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage

Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guérin (BCG) and to oxidative damage

IGF-1 may predict the severity and outcome of patients with sepsis and be associated with microRNA-1 level changes

Targeting Hsp90 in urothelial carcinoma

Contact Info

Product

Resources

About

H ₂ O ₂ Generation by bacillus Calmette-Guérin Induces the Cellular Oxidative Stress Response Required for bacillus Calmette-Guérin Direct Effects on Urothelial Carcinoma Biology