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1.
Artigo em Inglês | MEDLINE | ID: mdl-32360786

RESUMO

Long-term cognitive deficits are observed after treatment of brain tumors or metastases by radiotherapy. Treatment optimization thus requires a better understanding of the effects of radiotherapy on specific brain regions, according to their sensitivity and interconnectivity. In the present study, behavioral tests supported by immunohistology and magnetic resonance imaging provided a consistent picture of the persistent neurocognitive decline and neuroinflammation after the onset of irradiation-induced necrosis in the right primary somatosensory cortex of Fischer rats. Necrosis surrounded by neovascularization was first detected 54 days after irradiation and then spread to 110 days in the primary motor cortex, primary somatosensory region, striatum and right ventricle, resulting in fiber bundle disruption and demyelination in the corpus callosum of the right hemisphere. These structural damages translated into selective behavioral changes including spatial memory loss, disinhibition of anxiety-like behaviors, hyperactivity and pain hypersensitivity, but no significant alteration in motor coordination and grip strength abilities. Concomitantly, activated microglia and reactive astrocytes, accompanied by infiltration of leukocytes (CD45+) and T-cells (CD3+) cooperated to shape the neuroinflammation response. Overall, our study suggests that the slow and gradual onset of cellular damage would allow adaptation in brain regions that are susceptible to neuronal plasticity; while other cerebral structures that do not have this capacity would be more affected. The planning of radiotherapy, adjusted to the sensitivity and adaptability of brain structures, could therefore preserve certain neurocognitive functions; while higher doses of radiation could be delivered to brain areas that can better adapt to this treatment. In addition, strategies to block early post-radiation events need to be explored to prevent the development of long-term cognitive dysfunction.


Assuntos
Encéfalo/efeitos da radiação , Disfunção Cognitiva/psicologia , Encefalite/patologia , Encefalite/psicologia , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/psicologia , Animais , Comportamento Animal/efeitos da radiação , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Imagem de Difusão por Ressonância Magnética , Encefalite/diagnóstico por imagem , Vigilância Imunológica/efeitos da radiação , Imageamento por Ressonância Magnética , Masculino , Necrose , Neovascularização Patológica/patologia , Plasticidade Neuronal/efeitos da radiação , Lesões Experimentais por Radiação/diagnóstico por imagem , Ratos , Ratos Endogâmicos F344
2.
EBioMedicine ; 11: 165-172, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27475897

RESUMO

Laser therapy, recently renamed as photobiomodulation, stands as a promising supportive treatment for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. Here we explored the anti-cancer effect of 3 laser protocols, set at the most commonly used wavelengths, in B16F10 melanoma and oral carcinogenesis mouse models. While laser light increased cell metabolism in cultured cells, the in vivo outcome was reduced tumor progression. This striking, unexpected result, was paralleled by the recruitment of immune cells, in particular T lymphocytes and dendritic cells, which secreted type I interferons. Laser light also reduced the number of highly angiogenic macrophages within the tumor mass and promoted vessel normalization, an emerging strategy to control tumor progression. Collectively, these results set photobiomodulation as a safety procedure in oncological patients and open the way to its innovative use for cancer therapy.


Assuntos
Vigilância Imunológica/efeitos da radiação , Terapia a Laser , Neoplasias/imunologia , Neoplasias/patologia , Neovascularização Patológica , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/imunologia , Transformação Celular Neoplásica/efeitos da radiação , Modelos Animais de Doenças , Feminino , Humanos , Interferons/biossíntese , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Melanoma Experimental , Camundongos , Camundongos Knockout , Invasividade Neoplásica , Neoplasias/genética , Neoplasias/terapia , Neovascularização Patológica/terapia , Carga Tumoral/efeitos da radiação
3.
Cancer Radiother ; 18(5-6): 391-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25179250

RESUMO

Radiotherapy is along with surgery and chemotherapy one of the prime treatment modalities in cancer. It is applied in the primary, neoadjuvant as well as the adjuvant setting. Radiation techniques have rapidly evolved during the past decade enabling the delivery of high radiation doses, reducing side-effects in tumour-adjacent normal tissues. While increasing local tumour control, current and future efforts ought to deal with microscopic disease at a distance of the primary tumour, ultimately responsible for disease-progression. This review explores the possibility of bimodal treatment combining radiotherapy with immunotherapy.


Assuntos
Vigilância Imunológica/efeitos da radiação , Imunoterapia , Neoplasias/cirurgia , Radiocirurgia , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Efeito Espectador , Antígeno CTLA-4/antagonistas & inibidores , Morte Celular/imunologia , Morte Celular/efeitos da radiação , Terapia Combinada , Fracionamento da Dose de Radiação , Previsões , Humanos , Ipilimumab , Camundongos , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias Experimentais/cirurgia , Neoplasias Experimentais/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Evasão Tumoral/imunologia , Evasão Tumoral/efeitos da radiação , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/antagonistas & inibidores
6.
Immunol Today ; 15(4): 174-9, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8198709

RESUMO

Immune surveillance poses the existence of a recirculating pool of lymphocytes that migrate randomly through somatic tissues. Upon recognition of neoantigens on malignantly transformed cells, lymphocytes proceed to attack and destroy degenerate cells before a tumor emerges. Here, J. Wayne Streilein and colleagues review the effects of ultraviolet B irradiation on the induction of cutaneous immunity in the skin of mice and humans. Furthermore, they discuss the possibility of a genetic predisposition to skin cancer, mediated by a defect in the normal process by which contact hypersensitivity, and therefore immunogenicity, is elicited.


Assuntos
Vigilância Imunológica/efeitos da radiação , Neoplasias Induzidas por Radiação/imunologia , Neoplasias Cutâneas/imunologia , Pele/imunologia , Pele/efeitos da radiação , Luz Solar/efeitos adversos , Animais , Humanos , Camundongos , Neoplasias Cutâneas/etiologia , Raios Ultravioleta/efeitos adversos
8.
Adv Immun Cancer Ther ; 1: 1-28, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-3916661

RESUMO

Currently, the most probable theory of tumor surveillance is neither the existence of any tumor-specific, antigen-dependent, T-cell-mediated cytotoxic effect that could eliminate spontaneous tumors in man and that could be used for some kind of vaccination against tumors, nor the complete absence of any surveillance or defense systems against tumors. What is probable is the cooperation of a number of antigen-independent, relatively weakly cytotoxic or possibly only cytostatic humoral and cellular effects, including nutritional immunity, tumor necrosis factor, certain cytokines, and the cytotoxic effects mediated by macrophages, NK cells, NK-like cells, and certain stimulated T-cells. One question remaining to be solved is why these antigen-independent effects do not attack normal cells. A number of plausible hypotheses are discussed. The hypothetical surveillance system is modulated both by traditional cancer treatment and by attempts at immunomodulation. Radiotherapy reduced the T-helper cell function for almost a decade, but not those of macrophages or NK cells. T-cell changes have no prognostic implication, supporting, perhaps, the suggestion of a major role for macrophages and NK cells. Cyclic adjuvant chemotherapy reduces the peripheral lymphocyte population and several lymphocyte functions but not NK activity. Most of the parameters were normalized some years following treatment, but NK activity remained elevated and Th/Ts cell ratio was still decreased. This might possibly be taken to support the surveillance role of NK cells. Bestatin increases the frequency of lymphocytes forming rosettes with sheep red blood cells (but not their mitogenic responses), enhances NK activity, and augments the phagocytic capacity of granulocytes and monocytes (but not their cytotoxic activity). Improved survival with Bestatin treatment following chemotherapy has been observed in patients with melanoma Stages 1b and II and in patients with acute nonlymphatic leukemia, where BCG also seems active, although possibly only in patient groups with less than 49% complete remissions.


Assuntos
Adjuvantes Imunológicos/farmacologia , Antígenos de Neoplasias/imunologia , Antineoplásicos/farmacologia , Imunidade Celular , Vigilância Imunológica , Neoplasias/imunologia , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/efeitos da radiação , Vigilância Imunológica/efeitos dos fármacos , Vigilância Imunológica/efeitos da radiação , Células Matadoras Naturais/imunologia , Macrófagos/imunologia , Linfócitos T/imunologia
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