Molecular biology and targeted therapies for urothelial carcinoma

Seront, Emmanuel; Machiels, Jean‐Pascal

doi:10.1016/j.ctrv.2015.03.004

Cited by 45 publications

(38 citation statements)

References 117 publications

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“…Although the prediction models of BCa have achieved a great progress in recent years, more novel biomarkers are still required for improving the specificity and reliability of prediction tools for BCa14. Besides, the mainstream therapies for BCa, such as surgery, radiation and chemotherapy, still perform limited accuracy and efficacy151617. Thus, a better understanding of the molecular mechanisms involved in the pathogenesis of BCa and more attractive therapeutic approaches are definitely required.…”

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confidence: 99%

Theophylline controllable RNAi-based genetic switches regulate expression of lncRNA TINCR and malignant phenotypes in bladder cancer cells

Chen

Liu

et al. 2016

Sci Rep

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TINCR is a well-known lncRNA which acts as a master regulator in somatic differentiation development. However, it is still unclear whether TINCR is also involved in caner occurrence and progression. In this study, we observed that TINCR was up-regulated in bladder cancer tissues and cells and contributed to oncogenesis and cancer progression. Silencing TINCR expression inhibited cell proliferation and promoted apoptosis in vitro, indicating that TINCR may be the potential therapeutic target for treating bladder urothelial carcinoma. Thus we used the synthetic biology approach to create theophylline controllable RNAi-based genetic switches which silenced TINCR in a dosage-dependent manner. Both RNAi-OFF and ON switches can be used to quantitatively control the expression of TINCR in bladder cancer to suppress the progression of bladder cancer. These findings suggest that lncRNA-TINCR could promote bladder cancer development and progression and artificial control of its expression through inducible RNAi may represent a new kind of therapeutic strategy for treating human bladder cancer.

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confidence: 99%

Theophylline controllable RNAi-based genetic switches regulate expression of lncRNA TINCR and malignant phenotypes in bladder cancer cells

Chen

Liu

et al. 2016

Sci Rep

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“…Surgical resection, intravesical chemotherapy, and immunotherapy have been used to treat nonmuscle-invasive UC, and multimodality therapy, such as cystectomy and chemotherapy, is more appropriate for muscle-invasive UC. 4 Methotrexate, vinblastine, doxorubicin, and cisplatin were chemotherapeutic agents used to treat urothelial bladder cancer with ~50% response rate 5 and a survival of 15.2 months in a large randomized Phase III study. 6 However, methotrexate, vinblastine, doxorubicin, and cisplatin were associated with significant toxicities such as neutropenia and its infectious complications, as well as significant mucositis and a 4% drug-related death rate.…”

Section: Introductionmentioning

confidence: 99%

Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

Huang

Kuo

et al. 2016

IJN

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The effects against tumors exerted by marine active compounds have been highlighted and investigated. Polymeric nanoparticles made from biodegradable and biocompatible molecules such as hyaluronan (HA) and chitosan (CHI) are able to aggregate the compounds to enhance their activities against tumor cells and reduce the toxicity on normal cells. Here, we extensively examined the antitumor activities and the mechanisms of HA/CHI nanoparticles-aggregated heteronemin (HET) extracted from the sponge Hippospongia sp. The half-maximal inhibitory concentration (IC 50 ) of pure HET toward T24 bladder carcinoma cells is ~0.28 µg/mL. Pure HET from 0.2 to 0.8 µg/mL and HA nanoparticles-aggregated HET at 0.1 and 0.2 µg/mL significantly reduced T24 cell viability. Compared to pure HET, HA nanoparticles/HET aggregates showed much weaker viability-inhibitory effects on L929 normal fibroblasts. HET dose-dependently suppressed cancer cell migration as HA/CHI nanoparticles-aggregated HET displayed stronger migration-inhibitory effects than pure HET. Flow cytometric analysis showed that pure HET increased early/total apoptosis and JC-1 monomer fluorescence, while HA/CHI nanoparticles-aggregated HET induced higher apoptosis and JC-1 monomer rates than pure HET, suggesting that aggregation of HA nanoparticles offers HET stronger apoptosis-inducing capacity through mitochondrial depolarization. Western blot analysis showed that HA nanoparticles-aggregated HET further increased mitochondrial-associated, caspase-dependent and caspase-independent, as well as endoplasmic reticulum stress-related factors in comparison with pure HET. These data indicated that pure HET possesses cytotoxic, antimigratory, and apoptosis-inducing effects on bladder cancer cells in vitro, and its induction of apoptosis in bladder carcinoma cells is mainly caspase dependent. Moreover, HA nanoparticle aggregation reinforced the cytotoxic, antimigratory, and apoptosis-inducing activities against bladder carcinoma cells and attenuated the viability-inhibitory effects on normal fibroblasts. This aggregation reinforces antibladder carcinoma effects of HET via diverse routes, including mitochondrial-related/caspase-dependent, caspase-independent, and endoplasmic reticulum stress-related pathways. The current data also strongly suggested that HA/CHI nanoparticles-aggregated HET would be a potential treatment for urothelial cancer in vivo.

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“…Carboplatin-based combinations are associated with a median overall survival of 9 months, 2 and cisplatin-based combinations with a median overall survival of 12 to 15 months. 3 However, after platinum-based chemotherapy, there is no internationally accepted standard of care. Single-agent paclitaxel and docetaxel are commonly used worldwide, 4,5 and in Europe, vinflunine has been approved on the basis of an overall survival advantage of 2 months over best supportive care.…”

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confidence: 99%