RESUMO
Purpose: The COVID-19 pandemic brought several challenges to cancer practice, especially in ensuring continuity of treatment during this period while minimizing the risks of transmission to a vulnerable population. For radiation oncology departments in Brazil, this contingency has become even more complex owing to the significant effect observed in different sectors of society and the large number of COVID-19 cases and deaths. This study estimated the effect of the COVID-19 pandemic on Brazilian radiation oncology departments and the coping measures used in the country. Methods and Materials: The Brazilian Radiotherapy Society developed a questionnaire, with 14 questions, that were sent to all heads of radiation oncology departments in the country between May and June 2020. These data were evaluated regarding cases confirmed and deaths by COVID-19 in epidemiologic week 28, on July 11, 2020. Results: One hundred twenty-six questionnaires from different regions were answered, representing 44% of the country's services. A drop in the number of patients was observed in 61% of services. This drop was observed both in patients from the public and supplementary private health insurance systems. Regarding patients and employees with COVID-19, we observed that services that primarily treat Unified Health System patients reported significantly fewer cases of the disease. About half of the services had collaborators and patients during radiation therapy with a positive diagnosis of COVID-19. Among the coping measures, the services used intensified hygiene and cleanliness practices, interpersonal distancing, restrictions on access to companions, and other changes in daily practice. Conclusions: Thus, there was an important drop in the number of radiation therapy patients in the country during the pandemic, and this effect was similar among the services, regardless of the characteristics of the patients and the departments' coping measures adopted during the pandemic.
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BACKGROUND: NF-κB is a transcription factor involved in the transcriptional regulation of a large number of genes related to tumorigenesis in several cancer cell types, and its inhibition has been related to anticancer effect. DHMEQ (Dehydroxymethylepoxyquinomicin) is a compound that blocks the translocation of NF-κB from the cytoplasm to the nucleus, thus inhibiting its activity as a transcriptional activator. Several studies have shown the antineoplastic effects of DHMEQ in numerous tumor types, however, there are no surveys that tested their effects in MB. OBJECTIVES: The aim of the present study was to evaluate the effects of DHMEQ as NF-κB inhibitor in pediatric MB cell lines. METHOD: We used the UW402, UW473 and ONS-76 medulloblastoma (MB) cell lines to verify the effect of DHMEQ on proliferation, clonogenic capacity, apoptosis, cell invasion and migration, and evaluated the effect of the combination with other drugs and the potential as a radiosensitizator. RESULTS: A significant decrease in the cell growth, a strong inhibition of the clonogenic capacity, migration and cell invasion was observed after NF-κB inhibition in the three MB cell lines. Conversely, increased level of apoptosis rates were demonstrated. Additionally, treatments with DHMEQ combined with other chemotherapeutic agents were synergic in most points, and a strong radiosensitization by this compound was observed in the three MB cell lines. CONCLUSION: DHMEQ has potential antitumor effect on MB cells, and it may be considered a new therapeutic agent to improve treatment approaches in MB.
Assuntos
Antineoplásicos/farmacologia , Benzamidas/farmacologia , Cicloexanonas/farmacologia , Meduloblastoma/terapia , NF-kappa B/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Benzamidas/síntese química , Benzamidas/química , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cicloexanonas/síntese química , Cicloexanonas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Meduloblastoma/metabolismo , Estrutura Molecular , NF-kappa B/metabolismo , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Polo-like kinase 1 (PLK1), a key regulator of mitosis, is often overexpressed in childhood cancers and is associated with poor prognosis. Previous reports have shown that inhibition of PLK1 might serve as a promising anticancer treatment for osteosarcoma. In this study, we tested the second-generation PLK1 inhibitors BI 6727 and GSK461364 in HOS and MG-63 cell lines, both as a single agent and in combination with methotrexate, cisplatin, vinblastine, doxorubicin, or ionizing radiation. Both PLK1 inhibitors worked equally in terms of cell growth arrest, apoptosis induction, and radiosensitization. Combining BI 6727 or GSK461364 with conventional treatments, however, showed trivial synergistic antitumor effects in vitro. Our results reinforce the potential use of PLK1 inhibitors for a pharmacologic intervention in osteosarcoma, although their applicability in polychemotherapeutic regimens deserves further investigation.
Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Neoplasias Ósseas/patologia , Proliferação de Células/efeitos dos fármacos , Osteossarcoma/patologia , Inibidores de Proteínas Quinases/farmacologia , Pteridinas/farmacologia , Radiossensibilizantes/farmacologia , Tiofenos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Quinase 1 Polo-LikeRESUMO
Bladder cancer is a common malignancy worldwide. Despite the increased use of cisplatin-based combination therapy, the outcomes for patients with advanced disease remain poor. Recently, altered activation of the PI3K/ Akt/mTOR pathway has been associated with reduced patient survival and advanced stage of bladder cancer, making its upstream or downstream components attractive targets for therapeutic intervention. In the present study, we showed that treatment with DTCM-glutaramide, a piperidine that targets PDK1, results in reduced proliferation, diminished cell migration and G1 arrest in 5637 and T24 bladder carcinoma cells. Conversely, no apoptosis, necrosis or autophagy were detected after treatment, suggesting that reduced cell numbers in vitro are a result of diminished proliferation rather than cell death. Furthermore previous exposure to 10 µg/ml DTCM- glutarimide sensitized both cell lines to ionizing radiation. Although more studies are needed to corroborate our findings, our results indicate that PDK1 may be useful as a therapeutic target to prevent progression and abnormal tissue dissemination of urothelial carcinomas.