Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer

Autor: Denise Belgorosky, Ana María Eiján, Yanina Verónica Langle, Bárbara Patricia Prack Mc Cormick, Eduardo Omar Sandes, Natalia Patricia Balarino
Rok vydání: 2017
Předmět:
0301 basic medicine
Radiation-Sensitizing Agents
Cancer Research
Pathology
medicine.medical_specialty
CIENCIAS MÉDICAS Y DE LA SALUD
Cell Survival
Physiology
medicine.medical_treatment
In Vivo Vaccine
Clinical Biochemistry
Medicina Clínica
Biochemistry
Invasive Bladder Cancer
Oncología
Metastasis
Ciencias Biológicas
Mice
Necrosis
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
Radiation
Ionizing
medicine
Animals
Bacillus Calmette-Guerin
Bladder cancer
Tumor hypoxia
business.industry
Abscopal effect
Bioquímica y Biología Molecular
medicine.disease
Primary tumor
Mice
Inbred C57BL
Radiation therapy
Radiosensitizer
030104 developmental biology
Urinary Bladder Neoplasms
030220 oncology & carcinogenesis
Ionizing Radiation
BCG Vaccine
Immunogenic cell death
Tumor necrosis factor alpha
business
CIENCIAS NATURALES Y EXACTAS
Zdroj: Nitric Oxide. 64:22-30
ISSN: 1089-8603
DOI: 10.1016/j.niox.2017.01.008
Popis: BackgroundA key factor contributing to radio-resistance in conservative invasive bladder cancer (BCa) treatment is tumor hypoxia and a strategy to overcome it is to trigger the production of nitric oxide (NO). On the other hand, ionizing radiation (IR) applied to a primary tumor can induce immunogenic cell death which may set off a cytotoxic immune response against the primary tumor and its metastasis.PurposeTo study in vitro and in vivo, the role of BCG as a local sensitizer to overcome hypoxia-associated radio-resistance through the production of NO, and as an immune-stimulator to be used in combination with IR to generate a systemic response for invasive BCa treatment.Materials and methodsWe selected the invasive murine BCa cell line MB49-I which expresses inducible NO synthase and produces NO, cultured in vitro in 2D and 3D models, and inoculated in vivo in the subcutaneous of syngeneic mice.Resultsin vitro, multicellular murine invasive spheroids mimicked in vivo central tumor necrosis. BCG pre-treatment radio-sensitized spheroids through the induction of NO production, while no effect was shown in monolayers. In vivo, not only did BCG improve the local response to IR but it also decreased the metastatic spread and promoted the development of abscopal effect/rejection of a second tumor.ConclusionSince BCG has already and successfully been used for the treatment of non-invasive BCa and it improves the response to ionizing radiation in invasive BCa, these results are translational relevant to be analyzed in patients with this pathology. Fil: Prack Mc Cormick, Bárbara Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina Fil: Belgorosky, Denise. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina Fil: Langle, Yanina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina Fil: Balarino, Natalia Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina Fil: Sandes, Eduardo Omar. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina Fil: Eijan, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Databáze: OpenAIRE
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