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Molecular Assessment of non-muscle Invasive and muscle Invasive Bladder Tumors: Mapping of Putative Urothelial Stem Cells and Toll-Like Receptors (TLR) Signaling

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Journal of Cancer Therapy 2015年第2期6卷 129-140页

作者： Rafael Mamprin Stopiglia Wagner Eduardo Matheus Patrick Vianna Garcia Athanase Billis Mariana Anteghini Castilho Vitor Hugo Figueiredo de Jesus Ubirajara Ferreira Wagner José Fávaro Department of Urology School of Medicine University of Campinas-UNICAMP Sao Paulo Brazil Laboratory of Urogenital Carcinogenesis and Immunotherapy Institute of Biology University of Campinas-UNICAMP Sao Paulo Brazil Department of Pathology School of Medicine University of Campinas-UNICAMP Sao Paulo Brazil Botucatu School of Medicine Universidade Estadual Paulista-UNESP Botucatu Brazil

Purpose: The main objectives of this study were to characterize and compare the urothelial stem cells (healthy and cancer cells) and TLRs features in the urinary bladder of men without lesionsand with non-muscle-invasive and muscle invasive urothelial tumors. Materials and Methods: Thirty samples of the urinary bladder of 50 to 80-year-old men, with and without diagnosis of malignant urothelial lesions were used. The 30 samples were divided into 3 groups (n = 10 per group): Normal Group;non-muscle Invasive Bladder Cancer Group;muscle Invasive Bladder Cancer Group. The samples were histopathologically and immunohistochemically analyzed. The study was conducted at teaching Hospital of the University of Campinas (UNICAMP). Results: The CD44 and CD133 immunoreactivities were significantly intense in the muscle-invasive cancer group when compared to the other groups. The ABCG2 biomarker demonstrated intense immunoreactivities in both non-muscle and muscle invasive groups, and absent immunoreactivity in the normal group. All groups showed weak CD117 immunoreactivity. Putative Healthy Stem Cells (CD44/CD133/ CD117+) occurred in all groups. Putative Cancer Stem Cells (CD44/CD133/ABCG2+) only occurred in the non-muscle and muscle invasive cancer groups. TLR2 immunoreactivity was significantly lower in the non-muscle invasive cancer group and absent in the muscle invasive cancer group. TLR4 immunoreactivity was significantly lower in both cancer groups. Conclusions: This study leads us to the conclusion that putative cancer stem cell occurrence was sensitive to the decreased in TLR2 and TLR4 immunoreactivities. Also, TLR2 and TLR4 demonstrated their involvement in the regulation of the different biomarkers for putative healthy and cancer urothelial stem cells, probably acting as negative regulators of urothelial carcinogenesis. Taken together data obtained suggest that use of TLRs agonists could be a promising alternative for the treatment of non-muscle and muscle invasive bl

关键词： non-muscle Invasive Bladder Cancer muscle Invasive Bladder Cancer Toll-Like Receptors Cancer Stem Cell Stem Cells Biomarkers

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Recirculating chemohyperthermia as a treatment for non-muscle invasive bladder cancer:Current and future perspectives

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World Journal of Clinical Urology 2017年第2期6卷 34-39页

作者： Javier Flores-Carbajal Alejandro Sousa-Escandón Daniel Sousa-Gonzalez Silvia Rodriguez Gomez Manuel Lopez Saavedra M Elia Fernandez Martinez Comarcal Hospital of Monforte

About 75% of all bladder cancer diagnosed are non-muscle invasive bladder cancer(NMIBC), recurring over 50% of them after transurethral resection of the bladder tumor. In order to prevent recurrences, adjuvant intravesical chemotherapy with mitomycin C and immunotherapy with bacillus Calmette-Gu-érin(BCG) is traditionally used. Unfortunately, many patients relapse after receiving these treatments and a significant proportion of them require surgery. After a one-to-three years BCG maintenance, the risk for progression at 5 years was 19.3% for T1G3 tumors. Many new treatment approaches are being investigated to increase the effectiveness of adjuvant intravesical therapy. One of the developing treatments for intermediate and high-risk NMIBC is the combination of intravesical chemotherapy and hyperthermia, called chemohyperthermia. This article provides a review of the mechanism of action, current status and indications, results and future perspectives.

关键词： Bladder cancer Thermotherapy non-muscle invasive Chemohyperthermia Recirculating Intravesical chemotherapy Treatment Mechanism of action

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Markers for Diagnosis and Progression in Bladder Cancer

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Journal of Cancer Therapy 2012年第5期3卷 482-486页

作者： Josep M. Gaya Juan Palou Oscar Rodríguez Humberto Villavicencio Department of Urology Fundació Puigvert Universitat Autònoma de Barcelona Barcelona Spain

Bladder cancer is a common disease that is often detected late and has a high rate of recurrence and progression. The current standard of care for the primary detection and follow-up of NMIBC consists of urethro-cystoscopy associated with cytology. However, several clinical risk factors have been claimed to predict recurrence and progression, these factors have a predictive value on a population basis, but no parameter has been found that reliably predicts how an individual patient’s tumor will behave. In the last years many markers have been described in order to decrease the number of cystoscopies and try to provide individualized risk-stratified decision-making. We have focused our review in tumor markers for primary diagnosis, surveillance of non-muscle-invasive bladder cancer, and predicting progression to muscle-invasive disease. After our review, we can conclude that to the date no non-invasive biomarker has proven to be sensitive and specific enough to replace cystoscopy, neither in the diagnosis nor in the follow-up. On the other hand, promising results have been reported of potential biomarkers for predicting recurrence, early progression and poor response to BCG, new studies should be promoted to validate these results and make possible to incorporate markers as a new tool in clinical guidelines.

关键词： Bladder Cancer non-muscle Invasive Recurrence Progression Marker Urinary Marker Biomarker

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