Therapeutic interactions of autophagy with radiation and temozolomide in glioblastoma: evidence and issues to resolve

Koukourakis, Michael I.; Mitrakas, Achilleas; Giatromanolaki, Alexandra

doi:10.1038/bjc.2016.19

Cited by 65 publications

(60 citation statements)

References 117 publications

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“…Regarding the response to treatment, the results presented in this study agree with a review study 25 , which found a relationship between TMZ + RT therapy combination and an increase in survival in patients with glioma 7,8 .…”

supporting

confidence: 90%

Genetic variants related to angiogenesis and apoptosis in patients with glioma

Calastri

Rodrigues²,

Hatori

et al. 2018

Arq. Neuro-Psiquiatr.

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Background: Glioma, the most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. The objectives of this study were to evaluate the association of genetic polymorphisms related to angiogenesis and apoptosis with gliomas, as well as comorbidities, lifestyle, clinical profile, survival and response to treatment (temozolomide [TMZ] and radiotherapy [RT]) in patients with the disease. Methods: In a total of 303 individuals, genotypes were performed by real-time PCR, and clinical data, lifestyle and comorbidities were obtained from medical records and questionnaires. The significance level was set at 5%. Results: Smoking, alcohol consumption, systemic arterial hypertension, diabetes mellitus and body mass index prevailed among patients, compared to controls (p < 0.05). The heterozygous genotype rs1468727 (T/C) and the homozygous genotype rs2010963 (G/G) (p > 0.05) were observed in both groups. Lifestyle and comorbidities showed independent risk factors for the disease (p < 0.0001, p = 0.0069, p = 0.0394, respectively). Patients with low-grade gliomas had a survival rate of 80.0 ± 1.7% in three years. For the combination of TMZ+RT, survival was 78.7 ± 7.6% in 20 months, compared to TMZ only (21.9 ± 5.1%, p = 0.8711). Conclusions: Genetic variants were not associated with gliomas. Specific lifestyle habits and comorbidities stood out as independent risk factors for the disease. Low-grade gliomas showed an increase in patient survival with TMZ+RT treatment.Keywords: central nervous system; genes, erbB-1; glioblastoma. RESUMO Introdução: Glioma, tumor cerebral maligno, é altamente agressivo e associado a mau prognóstico. Os objetivos deste estudo foram avaliar a associação de polimorfismos genéticos relacionados a angiogênese e apoptose em pacientes com glioma, bem como suas comorbidades, hábitos de vida, perfil clínico, sobrevida e resposta ao tratamento (temozolomida [TMZ] e radioterapia [RT]). Métodos: 303 indivíduos foram genotipados por PCR em tempo real, e foram coletados dados clínicos, hábitos de vida e comorbidades. Admitiu-se nível de significância para valor p < 0,05. Resultados: Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal prevaleceram entre os pacientes, comprados aos controles (p < 0,05). O genótipo heterozigoto rs1468727 (T/C) e homozigoto rs2010963 (G/G) (p > 0,05) foram observados em ambos os grupos. Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal apresentaram fatores de risco independentes para a doença (p < 0.0001, p = 0.0069, p = 0.0394, respectivamente). Os pacientes com gliomas de baixo grau apresentaram sobrevida de 80,0 ± 1,7% em três anos. Para a combinação de RT e TMZ, a sobrevida foi de 78,7±7,6% em 20 meses, em comparação com TMZ (21,9 ± 5,1%, p = 0,8711). Conclusões: As variantes genéticas não estiveram associadas aos gliomas. Hábitos de vida e comorbidades específicas destacaram-se como fatores de risco independentes para a doen...

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supporting

confidence: 90%

Genetic variants related to angiogenesis and apoptosis in patients with glioma

Calastri

Rodrigues²,

Hatori

et al. 2018

Arq. Neuro-Psiquiatr.

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“…Yao et al [14] found that irradiation of human glioma cells led to increased autophagy. Another study [15] showed that the induction of autophagy by radiotherapy resulted in radioresistance of glioblastoma. However, little research has concentrated on the relationship between autophagy and radioresistance of bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

Chloroquine Enhances the Radiosensitivity of Bladder Cancer Cells by Inhibiting Autophagy and Activating Apoptosis

Wang

Tang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Chloroquine was formerly used as an anti-malarial agent drug but has now been proven to be useful for various diseases. This study aimed to investigate the radiosensitizing effect of chloroquine in bladder cancer, with an emphasis on autophagy inhibition and apoptosis induction. Methods: Bladder cancer cell lines were irradiated with or without chloroquine. Cell proliferation was determined by a Cell Counting Kit 8 assay. The radiosensitization effect of chloroquine was evaluated by clonogenic survival and progression of xenograft tumors. Cell apoptosis was detected by flow cytometry and western blot. Radiation-induced DNA double strand break was measured by the staining of γ-H2AX. In addition, autophagy was detected by western blot, immunofluorescence staining, and electron microscopy. Results: The treatment with chloroquine alone inhibited the proliferation of bladder cancer cells in a dose-dependent manner. Low cytotoxic concentrations of chloroquine enhanced the radiation sensitivity of bladder cancer cells with a sensitization enhancement ratio of 1.53 and 1.40. Chloroquine also obviously weakened the repair of radiation-induced DNA damage. A combination of radiation and chloroquine enhanced the apoptosis rate of EJ and T24 cells and down-regulated the expression of Bcl-2 while up-regulating the expression of caspase-3. Additionally, the relevant markers of autophagy were obviously increased in the combined group, meaning that chloroquine inhibited autophagy induced by irradiation. Furthermore, subcutaneous xenograft tumors displayed that the combination of radiation and chloroquine could impede tumorigenesis in vivo. Conclusion: In summary, these results provided support that by inhibiting autophagy and activating apoptosis, chloroquine might be a potentially promising radiosensitizer in the radiation therapy of bladder cancer.

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“…Unlike low-grade gliomas, the complete surgical removal of glioblastoma is impossible due to the infiltrative nature of the disease and functional vulnerability of the brain [6]. Postoperative radiotherapy with the administration of temozolomide (TMZ) and local delivery of ACNU could remove most of the residual glioma cells, but not glioma stem cells.…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Intranasal GM-CSF enhances efficacy of local ACNU delivery rendezvousing with TMZ plus irradiation in glioblastoma

Yang¹,

Bu²,

Xue³

et al. 2018

Oncotarget

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This study aims to investigate the efficacy and safety of intranasal granulocytemacrophage colony stimulating factor (GM-CSF) treatment rendezvousing with chemoradiotherapy for post-operative glioblastoma patients. A total of ninety-two patients were randomized into two groups: control group (n = 46), patients who received radiotherapy with concomitant and adjuvant local delivery of nimustine hydrochloride (ACNU) rendezvousing with systemic administration of temozolomide (TMZ); observation group (n = 46), patients who received intranasal GM-CSF prior to each cycle of adjuvant chemotherapy based on the control group. Karnofsky performance status (KPS) scores, progression-free survival (PFS), overall survival (OS) and adverse effects were compared between these two groups. Two patients in the control group were excluded due to grade 3 hematologic toxicity. Furthermore, the observation group was superior to the control group with regard to PFS (7.8 months vs. 6.9 months, P = 0.016) and OS (19.2 months vs. 17.1 months, P = 0.045 without adjustment for interim analyses). KPS scores was higher in the observation group than in the control group after six months (84.35 ± 8.86, 80.65 ± 7.72; t = 4.552, P = 0.036). Neutropenia and thrombocytopenia decreased in the observation group, with incidences of 8.7% and 8.7%, respectively, when compared with the control group (29.5% and 18.2%, respectively; P = 0.012); while other adverse events were similar in both groups. Most adverse events were grade I-II and resolved spontaneously. Intranasal GM-CSF enhances the efficacy of the local delivery of ACNU rendezvousing with oral TMZ chemotherapy associated with significantly improved survival and quality of life in glioblastoma patients after surgery. This therapy could relieve chemotherapy related neutropenia, and does not increase the adverse events of other aspects.www.impactjournals.com/oncotarget/

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Therapeutic interactions of autophagy with radiation and temozolomide in glioblastoma: evidence and issues to resolve

Cited by 65 publications

References 117 publications

Genetic variants related to angiogenesis and apoptosis in patients with glioma

Genetic variants related to angiogenesis and apoptosis in patients with glioma

Chloroquine Enhances the Radiosensitivity of Bladder Cancer Cells by Inhibiting Autophagy and Activating Apoptosis

WITHDRAWN: Intranasal GM-CSF enhances efficacy of local ACNU delivery rendezvousing with TMZ plus irradiation in glioblastoma

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