RESUMO
There are no effective strategies for the successful treatment of glioblastomas (GBM). Current therapeutic modalities effectively target bulk tumor cells but leave behind marginal GBM cells that escape from the surgical margins and radiotherapy field, exhibiting high migratory phenotype and resistance to all available anti-glioma therapies. Drug resistance is mostly driven by tumor cell plasticity: a concept associated with reactivating transcriptional programs in response to adverse and dynamic conditions from the tumor microenvironment. Autophagy, or "self-eating", pathway is an emerging target for cancer therapy and has been regarded as one of the key drivers of cell plasticity in response to energy demanding stress conditions. Many studies shed light on the importance of autophagy as an adaptive mechanism, protecting GBM cells from unfavorable conditions, while others recognize that autophagy can kill those cells by triggering a non-apoptotic cell death program, called 'autophagy cell death' (ACD). In this review, we carefully analyzed literature data and conclude that there is no clear evidence indicating the presence of ACD under pathophysiological settings in GBM disease. It seems to be exclusively induced by excessive (supra-physiological) stress signals, mostly from in vitro cell culture studies. Instead, pre-clinical and clinical data indicate that autophagy is an emblematic example of the 'dark-side' of a rescue pathway that contributes profoundly to a pro-tumoral adaptive response. From a standpoint of treating the real human disease, only combinatorial therapy targeting autophagy with cytotoxic drugs in the adjuvant setting for GBM patients, associated with the development of less toxic and more specific autophagy inhibitors, may inhibit adaptive response and enhance the sensibility of glioma cells to conventional therapies.
RESUMO
The case of a woman with systemic lupus erythematosus and coexistent milky ascites and meningitis by Listeria monocytogenes is reported. The patient was under longstanding immunosuppressive treatment. Listeriosis is considered an uncommon condition in adults, which occurs as opportunistic infection in immunosuppressed hosts. Samples from ascites showed low triglyceride concentration. Opalescent ascites and Listeria meningitis are rarely reported inpatients with systemic lupus erythematosus.
Relata-se o caso de uma mulher com lúpus eritematoso sistêmico e ascite leitosa coexistente com meningite por Listeria monocytogenes. A paciente estava em tratamento imunossupressivo de longa duração. A listeriose é considerada doença incomum em adultos, que ocorre como infecção oportunista em hospedeiros imunossuprimidos. Amostras da ascite revelaram baixa concentração de triglicérides. Ascite opalecente e meningite por Listeria são raramente descritas em pacientes com lúpus eritematoso sistêmico.