RESUMEN
Hypoxia is a common feature of malignant tumors. There is an interactive connection between hypoxia and chemoresistance, radioresistance, invasiveness, and angiogenesis. Therefore, tumor hypoxia has been considered as a validated target for treating cancer. This review focuses on the role of hypoxia on chemoresistance and radioresistance. In addition, we address several approaches targeting tumor hypoxia, known as hypoxia-targeted therapy.
Asunto(s)
Hipoxia/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Terapia Combinada , Resistencia a Antineoplásicos , Terapia Genética , Humanos , Hipoxia/genética , Hipoxia/inmunología , Factor 1 Inducible por Hipoxia/genética , Factor 1 Inducible por Hipoxia/metabolismo , Inmunidad , Terapia Molecular Dirigida , Neoplasias/genética , Neoplasias/inmunología , Tolerancia a Radiación , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
In addition to its anticonvulsant effect, low frequency stimulation (LFS) improves learning and memory in kindled animals. In the present study, the role of 5-HT1A receptors in mediating LFS' improving effect on spatial learning and memory was investigated in amygdala-kindled rats. Amygdala kindling was conducted in a semi-rapid kindling stimulations (12 stimulations per day) in male Wistar rats. LFS (4 trains of 0.1 ms pulse duration at 1 Hz, 200 pulses, 50-150 µA, at 5 min intervals) was applied after termination of kindling stimulations. NAD-299 (a selective 5-HT1A receptor antagonist; 2.5 and 5 µg/µl) was microinjected into the hippocampal CA1 before applying LFS. The Morris water maze, and novel object recognition tests were conducted after the last kindling stimulation. Hippocampal samples were also prepared, and 5-HT1A receptor gene expression levels were assessed using quantitative RT-PCR. In kindled animals, LFS reduced impairments in spatial learning and memory in the Morris water maze and novel object recognition tests. Microinjection of NAD doses of 5 µg/µl reduced the effects of LFS on learning and memory. The gene expression level of 5-HT1A receptors increased significantly in the hippocampus of amygdala-kindled rats. However, LFS applied after kindling stimulations inhibited this effect. It seems that activation of 5-HT1A receptors in the CA1 field is necessary for LFS' improving effects on spatial learning and memory in kindled animals; although surprisingly, LFS application prevented the elevation in gene expression of 5-HT1A receptors in kindled animals.