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Toll like receptors and urinary bladder carcinoma

Tom J H Arends, Rianne J M Lammers, Johannes Falke, Antoine G van der Heijden, Irene Rustighini, Raffaella Pozzi, Miroslav Ravic, Andreas Eisenhardt, Henk Vergunst, J Alfred Witjes
INTRODUCTION/BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) has a strong tendency to recur despite adjuvant instillations. TMX-101 is a new liquid form of imiquimod for intravesical instillation and has activity in vitro against urothelial carcinoma. The purpose was to analyze the activity of TMX-101 in low-grade NMIBC. Furthermore, pharmacokinetic and pharmacodynamic characteristics and adverse events were evaluated. PATIENTS AND METHODS: A multicenter, prospective phase 1 trial in 7 patients with low-grade NMIBC was conducted...
June 2015: Clinical Genitourinary Cancer
Johannes Falke, Rianne J M Lammers, Harm C Arentsen, Miroslav Ravic, Raffaella Pozzi, Erik B Cornel, Henk Vergunst, Theo M de Reijke, J Alfred Witjes
PURPOSE: Imiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: We conducted a multicenter phase 1 dose escalation study in patients with nonmuscle invasive bladder cancer. Patients were included in 1 of 4 dose groups (0.05%, 0.1%, 0.2% or 0...
June 2013: Journal of Urology
Tomoyuki Kato, Vladimir Bilim, Kaori Yuuki, Sei Naito, Takuya Yamanobe, Akira Nagaoka, Ikuya Yano, Hideyuki Akaza, Yoshihiko Tomita
AIM: Bacillus Calmette-Guerin (BCG) is one of therapeutic options for urothelial carcinoma (UC). The objectives of this study were to determine the direct effect of viable or heat-killed BCG and BCG cell wall skeleton (BCG-CWS) on UC cells in vitro. MATERIALS AND METHODS: UC cell lines were co-cultured with viable or heat-killed BCG Immunobladder® (Tokyo 172 strain) and BCG-CWS. Viability of the cells, apoptosis and BrdU incorporation were estimated. RESULTS: BCG induced cell growth retardation in highly malignant UC bearing integrin α5β1 (VLA5)...
October 2010: Anticancer Research
Jian-an Wei, Xing Zeng, Ling Han, Yu Huang
OBJECTIVE: To establish a murine bladder cancer cell line with stable silencing of toll-like receptor 2 (TLR2) expression. METHODS: Three different recombinant plasmids pcDNA 6.2-GW/EmGFPmiR-TLR2 were constructed and transfected into T739 cells via lipofectamine. The recombinant plasmid with the strongest interference effect was selected by RT-PCR and transfected into T739 cells. The Blasticidin-resistant cell clones were screened to obtain bladder cancer cell lines with TLR2 gene knockdown, and the biological characteristics of the stable cell lines were observed...
August 2010: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Carl-Jørgen Arum, Endre Anderssen, Karin Tømmerås, Steiner Lundgren, Duan Chen, Chun-Mei Zhao
OBJECTIVES: To reveal the gene expression profile and pathways involved in host-tumor interactions in a rat orthotopic syngeneic bladder cancer model. METHODS: Rat bladder cancer cells (AY-27 cell line) were inoculated intravesically into female Fischer rats. The bladders were analyzed at 7, 14, and 28 days by histologic examination and at 14 days with Affymetrix GeneChip with a newly developed bioinformatics program for the Kyoto Encyclopedia of Genes and Genomes (KEGG)...
March 2010: Urology
Peter Jochen Olbert, Andres Jan Schrader, Corinna Simon, Alexander Dalpke, Peter Barth, Rainer Hofmann, Axel Hegele
BACKGROUND: Intravesical BCG instillation is established and efficient in the prophylaxis of recurrent transitional cell carcinoma. A Th-1 biased immune response is postulated. Recent work has proven the efficacy of synthetic CpG-Oligodeoxynucleotides (ODN) as inducers and adjuvants for a strong Th1-response and there is evidence for a direct and/or adjuvant anti-neoplastic effect. The purpose of this study was to examine the local effects of CpG-ODN on the murine bladder wall after intravesical instillation and the effects on cytokine expression in an orthotopic murine bladder cancer model...
June 2009: Anticancer Research
Yigang Qian, Junfang Deng, Lei Geng, Haiyang Xie, Guoping Jiang, Lin Zhou, Yan Wang, Shenyong Yin, Xiaowen Feng, Junwei Liu, Zhou Ye, Shusen Zheng
TLR4 (Toll-like receptor 4) and B7-H1, which were known to be restricted to immune cells in the past, were found to be aberrantly expressed in a majority of tumor cells, facilitating tumor evasion from immune surveillance. Our study demonstrated that activation of TLR4 signaling in bladder cancer cells up-regulated B7-H1 expression. Furthermore, this regulation was significantly attenuated by ERK or JNK inhibitor. Our results elucidated the molecule mechanism of regulation of B7-H1 expression through TLR4 signaling and may suggest new strategies of down-regulating the cancer-associated B7-H1 expression for bladder cancer treatment...
October 2008: Cancer Investigation
Huixian Liu, Michael J Schwartz, David H Hwang, Douglas S Scherr
OBJECTIVE: To detect and characterize the potential role of c-Myc in the inhibition of proliferation and induction of cell death of urothelial cell carcinoma by imidazoquinolines, Toll-like receptor-7 (TLR7) agonists, that are thought to exert their immunogenic effects through the MyD88/NF-kappaB pathway. MATERIALS AND METHODS: Human (T24) and murine (MBT-2) bladder cancer cell lines were cultured in normal culture medium or medium supplemented with imidazoquinoline...
April 2008: BJU International
Chi-Chen Lin, Huei-Jiun Yang, Cheng-Fen Tu, Ming-Derg Lai
DNA vaccine represents a novel method to elicit immunity against infectious disease. Lipopolysaccharide (LPS) copurified with plasmid DNA may affect therapeutic efficacy and immunological response. We aimed to study the effect of LPS on the therapeutic efficacy of HER-2/neu DNA vaccine in a mouse tumor animal model. Plasmid DNA purified from commercial EndoFree plasmid purification kits functioned as a better therapeutic DNA vaccine than that purified from Non-EndoFree purification kit, which contains >or=0...
March 2008: DNA and Cell Biology
Eric B Smith, Michael Schwartz, Hideki Kawamoto, Xueke You, David Hwang, Huixian Liu, Douglas S Scherr
PURPOSE: Imidazoquinolines (Toll-like receptor-7 agonists) are a class of synthetic immune modulating agents. Imiquimod, a member of this drug family, is currently used as first line topical therapy for genital condyloma. It recently showed clinical efficacy against several benign and malignant skin lesions, including actinic keratosis and basal cell carcinoma. Working primarily through the stimulation of a proinflammatory immune response, the mechanism of action of imiquimod may be similar to that through which bacillus Calmette-Guerin is thought to act...
June 2007: Journal of Urology
Xiang Li, Zhi-yong Gong, Ming Shi, Qiang Wei, Hong Li, Yu-ru Yang
OBJECTIVE: To investigate and compare the expression of Toll-like receptors (TLRs) in human bladder cells under the stimulus of Escherichia coli (E. coli) versus that under the stimulus of Bacillus Calmette-Guérin (BCG). METHODS: Human bladder cancer cell line T24 was cultured for 1 hour under the stimuli of various doses (bacillus-cell ratio) of E. coli and BCG respectively. The levels of expression of TLR-2 and TLR-4 mRNA in T24 cells were assessed by RT-PCR method...
May 2004: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
Xiang Li, Zhi-yong Gong, Hong Li, Qiang Wei, Ming Shi, Yu-ru Yang
OBJECTIVE: To investigate the effect of bacillus Calmette-Guerin (BCG) on Toll-like receptors (TLRs) expression and cytokine production in human bladder cancer cell line T24. METHODS: Human transitional carcinoma cell line T24 was cultured in RPMI1640 medium with 10% FBS, BCG was added into the cell culture with various doses in bacteria-cell ratio. After T24 cells were stimulated by BCG for 1 hour, total RNA of cells was extracted. RT-PCR procedure was conducted with the primer of TLR-2 and TLR-4, and the products were analyzed with agarose gels electrophoresis...
February 7, 2004: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
H Atkins, B R Davies, J A Kirby, J D Kelly
Intravesical bacillus Calmette-Guerin (BCG) is a treatment for transitional cell carcinoma (TCC) and carcinoma in situ (cis) of the urinary bladder, but some patients remain refractory. The mechanism of cancer clearance is not known, but T cells are thought to play a contributory role. Tissue dendritic cells (DCs) are known to initiate antigen-specific immune responses following activation of receptors, which recognise molecular patterns on the surface of microorganisms. A family of these receptors, the toll-like receptors (TLRs), are also crucial for activating DC to produce cytokines that polarise the T-cell response towards a T helper (Th)1 or Th2 phenotype...
December 15, 2003: British Journal of Cancer
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