Necessidades de aprendizagem de familiares de crianças e adolescentes em tratamento com quimioterápicos antineoplásicos orais / Necesidades de aprendizaje de los familiares de niños y adolescentes en tratamiento con quimioterapia antineoplástica oral / Learning needs of relatives of children and teenagers under oral antineoplastic chemotherapy treatment

RESUMO Objetivo descrever as necessidades de aprendizagem de familiares de crianças e adolescentes com câncer quanto ao tratamento com quimioterápicos antineoplásicos orais. Método pesquisa qualitativa descritiva desenvolvida em um hospital federal do Rio de Janeiro, Brasil. Os dados foram coletados nos meses de julho a setembro de 2020 a partir de entrevistas semiestruturadas com vinte e três familiares de crianças e adolescentes com câncer em quimioterapia antineoplásica oral. Os dados foram processados no software Interface de R pour Analyses Multidimensionnelles de Textes et de Questionnaires pela Classificação Hierárquica Descendente. Resultados dentre os temas que demandam aprendizagem pelos familiares estão administração oral, armazenamento e manipulação dos quimioterápicos orais, além dos efeitos adversos e emergências que demandam atendimento hospitalar. Conclusão e implicações para a prática no tratamento com quimioterápicos orais, as necessidades de aprendizagem dos familiares de crianças e adolescentes precisam ser problematizadas em práticas educativas dialógicas para, assim, favorecer a segurança, a adesão e a eficácia do tratamento.

RESUMEN Objetivo describir las necesidades de aprendizaje de familiares de niños y adolescentes con cáncer en cuanto al tratamiento con quimioterápicos antineoplásicos orales. Método investigación cualitativa descriptiva desarrollada en un hospital federal de Río de Janeiro, Brasil. Los datos fueron recogidos en los meses de julio a septiembre de 2020 a partir de entrevistas semiestructuradas con veintitrés familiares de niños y adolescentes con cáncer en quimioterapia antineoplásica oral. Los datos fueron procesados en el software Interface de R pour Analyses Multidimensionnelles de Textes et de Questionnaires por la Clasificación Jerárquica Descendente. Resultados entre los temas que demandan aprendizaje por los familiares están administración oral, almacenamiento y manipulación de los quimioterápicos orales, además de los efectos adversos y emergencias que demandan atención hospitalaria. Conclusión e implicaciones para la práctica en el tratamiento con quimioterápicos orales, las necesidades de aprendizaje de los familiares de niños y adolescentes necesitan ser problematizadas en prácticas educativas dialógicas para, así, favorecer la seguridad, la adhesión y la eficacia del tratamiento.

ABSTRACT Objective to describe the learning needs of family members of children and adolescents with cancer regarding treatment with oral antineoplastic chemotherapies. Method a descriptive qualitative research developed in a federal hospital in Rio de Janeiro, Brazil. Data were collected in the months from July to September 2020 from semi-structured interviews with twenty-three family members of children and adolescents with cancer undergoing oral antineoplastic chemotherapy. Data was processed in the software Interface de R pour Analyses Multidimensionnelles de Textes et de Questionnaires by the Descending Hierarchical Classification. Results among the themes that demand learning by the family members are oral administration, storage and handling of oral antineoplastic drugs, as well as adverse effects and emergencies that require hospital care. Conclusion and implications for practice in oral antineoplastic treatment, the learning needs of family members of children and adolescents need to be problematized in dialogic educational practices in order to favor the safety, adherence, and efficacy of the treatment.

Inhibition of Ciliogenesis Enhances the Cellular Sensitivity to Temozolomide and Ionizing Radiation in Human Glioblastoma Cells / 生物医学与环境科学（英文）

Objective@#To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM).@*Methods@#GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay.@*Results@#Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation.@*Conclusion@#Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.

Primary Extra-axial Glioblastoma: Case Report and Literature Review

Glioblastoma multiforme (GBM) is the most frequent and most aggressive primary brain tumor in adults,mainly located in the cerebral hemispheres. In the literature, few cases of primary GBM have been reported to have radiographic and intraoperative features of extra-axial lesions, leading to a diagnostic dilemma. Despite the advances in imaging modalities, the diagnosis of GBM can be challenging, and it is mainly based on the histopathologic confirmation of the excised tumor. We describe the case of a 76- year-old previously healthy female patient who presented to our hospital due to speech disturbances and cognitive impairment. The diagnosis of the tumor type on magnetic resonance imaging (MRI) was difficult, as the findings were suggestive of a malignant meningioma due to the heterogeneous enhancement of a dural-based mass with a dural tail sign. Moreover, the intraoperative findings revealed an extra-axial mass attached to the dura. A histological examination confirmed the diagnosis of glioblastoma with arachnoid infiltration. The patient underwent adjuvant radiotherapy and concomitant temozolomide treatment, she had clinical improvement postoperatively, and was stable during the six months of follow-up. Glioblastoma should be considered in the differential diagnosis of primary extra-axial mass with atypical and malignant features, especially in elderly patients.

Establishment of a mouse model bearing orthotopic temozolomide-resistant glioma / 南方医科大学学报

OBJECTIVE@#To establish a mouse model bearing orthotopic temozolomide (TMZ)-resistant glioma that mimics the development of drug resistance in gliomas @*METHODS@#Seventy-eight adult C57BL/6 mice were randomly divided into 6 groups (@*RESULTS@#The mouse models bearing TMZresistant glioma was successfully established. The cells from the high-dose induced group showed a significantly higher colony-forming rate than those from the high-dose control group (@*CONCLUSIONS@#Progressive increase of TMZ doses in mice bearing orthotopic gliomas can effectively induce TMZ resistance of the gliomas.

Clinical Efficacy of High Dose Methotrexate, Temozolomide and Rituximab in the Treatment of Patients with Primary Central Nervous System Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical efficacy of high dose methotrexate (HD-MTX), temozolomide (TMZ), and rituximab (R) in the treatment of patients with primary central nervous system lymphoma (PCNSL).@*METHODS@#Clinical data of patients with PCNSL diagnosed and treated in Guangdong Provincial People's Hospital from February 2010 to May 2017 were collected. First, patients were given 6-8 cycles of MTX (3.5 g/m@*RESULTS@#There were 42 patients enrolled in the study, 17 cases in HD-MTX+TMZ group and 25 cases in HD-MTX+TMZ+R group. The median PFS and OS times in HD-MTX+TMZ+R group were 56.7 months and N/A, respectively, while, 7.3 months and 34.7 months in HD-MTX+TMZ group, respectively. In addition, there was no significant difference in median survival between patients who received TMZ maintenance therapy and those who were only actively monitored. During the induction period, all the patients had grade 1-2 nausea and vomiting, while in the consolidation treatment period, no grade 3/4 toxicity was observed.@*CONCLUSION@#The combination of HD-MTX+TMZ+R in the treatment of PCNSL patients shows a definite short-term effect, which can increase the survival rate of the patients. The side effects are mild, and the patients can generally tolerate.

Patterns of recurrence and outcomes of glioblastoma multiforme treated with chemoradiation and adjuvant temozolomide

OBJECTIVES: To assess the patterns of failure and prognostic factors in Brazilian patients with glioblastoma multiforme (GBM) treated with radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ). METHODS: Patients with diagnosed GBM post-resection received postoperative RT. TMZ was administered concurrently at 75 mg/m2/day for 28 consecutive days and adjuvant therapy at 150-200 mg/m2/day for 5 days every 28 days. Radiographic failure was defined as any new T1-enhancing lesion or biopsy-confirmed progressive enhancement inside of the radiation field. When possible, patients with recurrence were salvaged with metronomic TMZ, either in combination with a local treatment or alone (surgery or re-irradiation). Several prognostic factors were evaluated for overall survival (OS). Univariate and multivariate analyses were performed to identify significant factors. A p-value <0.05 was considered significant. RESULTS: This study included 50 patients. The median follow-up time was 21 months. The median RT dose was 60 Gy and all patients received concomitant TMZ. During follow-up, 41 (83.6%) failures were observed, including 34 (83%) in-field, 4 (9.7%) marginal, and 3 (7.3%) distant failures. Metronomic TMZ was used as salvage treatment in 22 (44%) cases and in combination with local treatment in 12 (24%) cases. The median OS and progression-free survival times for the entire cohort were 17 and 9 months, respectively. In univariate analysis, the following factors were significant for better OS: maximal surgical resection (p=0.03), Karnofsky Performance Score (KPS)>70 at diagnosis (p=0.01), metronomic TMZ treatment (p=0.038), recursive partitioning analysis class III (p=0.03), and time to failure >9 months (p=0.0001). In multivariate analysis, the following factors remained significant for better OS: metronomic TMZ (p=0.01) and time to failure >9 months (p=0.0001). CONCLUSION: The median OS of Brazilian patients with GBM treated with RT and TMZ was satisfactory. Although TMZ therapy has become the standard of care for patients with newly diagnosed GBM, the recurrence rate is extremely high. Metronomic TMZ as salvage treatment improved survival in these patients.