Both p53 codon 72 Arg/Arg and pro/Arg genotypes in glioblastoma multiforme are associated with a better prognosis in bevacizumab treatment.

BACKGROUND: It has previously been shown that bevacizumab, when added to chemotherapy, improved overall survival in several cancers. In glioblastoma multiforme (GBM), bevacizumab increased progression-free survival and it is widely used for tumor recurrence, though it has failed to improve overall survival (OS) in controlled trials. However, an effective biomarker for predicting the prognosis of bevacizumab treatment has yet to be identified. This study, therefore, aimed to retrospectively analyze the polymorphisms of p53 codon 72 and the clinical characteristics of GBM specimens from Taiwanese patients. METHODS: The polymorphisms of p53 codon 72 in 99 patients with GBM treated at Taichung Veterans General Hospital in Taiwan from 2007 to 2017 were analyzed using direct DNA sequencing and PCR-RFLP analysis. RESULTS: We found that among these GBM patients, the distribution of codon 72 polymorphisms was 28.3% for proline homozygotes (Pro/Pro), 38.4% for arginine homozygotes (Arg/Arg), and 33.3% for proline/arginine heterozygotes (Pro/Arg). Although the polymorphisms of p53 codon 72 were not directly associated with the overall survival of GBM, both the Arg/Arg and Arg/Pro genotypes were associated with significant benefits in terms of overall survival in patients treated with CCRT plus bevacizumab compared to patients treated with CCRT alone. CONCLUSIONS: This pilot study suggests that both the Arg/Arg and Arg/Pro genotypes of p53 codon 72 polymorphism may have value as independent prognostic or predictive parameters for bevacizumab treatment response and failure. Relatedly, the results of the study further demonstrate the utility of stratifying GBM patients according to bevacizumab sensitivity.

Malignant transformation of craniopharyngioma with detailed follow-up.

A 29-year-old male patient was admitted into hospital with the main complaint of progressive visual disturbance. Both CT SCAN and MRI demonstrated a cystic-solid contrast-enhancing sellar-suprasellar mass with obvious calcification. Histopathological examination of the first resected specimen showed a typical appearance of adamantinomatous craniopharyngioma. The patient received gamma knife therapy after his first operation because of partial tumor removal. He experienced two relapses in the subsequent 2 years, for which only surgical resection was performed. The later histopathology presented malignant appearance with tumor cells moderate to severe pleomorphism, hyperchromasia, increased nuclear cytoplastic ratio, high mitotic activity (30/10 high power fields) and focal coagulative necrosis. The patient died 9 months after identification of histologic malignancy. Clinical and histopathological features, biological behavior of one case of malignant craniopharyngioma were discussed, with a brief review of the relevant literature.

Inhibition of lymphoma cell proliferation by peroxisomal proliferator-activated receptor-γ ligands via Wnt signaling pathway.

Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in regulating energy balance, glucose and lipid metabolisms and inflammation. PPARγ also exerts multiple anti-cancer effects including tumor growth and angiogenesis inhibition, induction of cell differentiation, and apoptosis. Perturbed Wnt/ß-catenin signaling likely plays a key role in tumorigenesis and the interaction between PPARγ and the transcriptional regulator ß-catenin maybe important in this process. Phosphorylation of ß-catenin by GSK-3ß inactivates it and suppresses tumor cell proliferation and self-renewal of tumor stem cells. In combination with Frizzled, Wnt suppresses GSK-3ß and causes degradation of ß-catenin and activation of many tumor proliferation factors. In the present study, we investigated the effects of PPARγ agonist rosiglitazone (RGZ) and PPARγ antagonist GW9662 on the growth, mitotic cycle, and apoptosis of human lymphoma cell line, Raji cells. We also studied the influence of PPARγ ligands on the expression of ß-catenin and GSK-3ß in Raji cells to reveal whether Wnt/GSK-3ß/ß-catenin signaling pathways are involved in PPARγ ligands triggered Raji cell apoptosis. Results showed that both RGZ and GW9662 can inhibit the growth of Raji cells by inducing apoptosis and arresting cell cycle; however, there was no correlation between these effects and expression of PPARγ. Both the PPARγ ligands, RGZ and GW9662, appear to reciprocally regulate the mRNA and protein expressions of GSK-3ß, which promotes apoptosis, and of ß-catenin, which blocks apoptosis. These results suggest that PPARγ ligands mediate their effects via Wnt/GSK-3ß/ß-catenin signaling on Raji cell proliferation and survival.

Drug or vaccine?: selecting the appropriate treatment for malignant glioma patients.

Malignant gliomas are the most common and aggressive form of brain tumour. Current combinations of aggressive surgical resection, radiation therapy and chemotherapy regimens do not significantly improve long-term patient survival for these cancers. Therefore, investigative therapies including tumour vaccines have targeted this devastating condition. This article reviews evidence and data on chemotherapy and immunotherapy for a personalized medicine approach in order to enable physicians to select the appropriate treatment for glioma patients. Dendritic cell- and peptide-based therapy for gliomas seems to be safe and without major adverse effects. Gene-modified vaccines have also shown promise in the treatment of malignant gliomas. The concept of 'personalized medicine' is currently important in oncology treatment development. Using a personalized medicine approach, it may be necessary to evaluate the molecular genetic abnormalities in individual patient tumours, and such findings should be the mainstay of immunotherapeutic strategies designed for the individual patient.

Analysis and prevention of cerebral infarction in patients with traumatic brain injury.

We reviewed the clinical data of 32 cases of cerebral infarction after traumatic brain injury, aiming to explore the pathogenesis and assess the prognosis of the condition so as to find effective prevention and treatment measures. According to Glasgow Outcome Scale (GOS) scores, 12 patients were classified as having good recovery, 5 moderate neurological deficit, 4 severe neurological deficit, and 3 in vegetative state. Death occurred in 8 cases. These results indicate the mortality and morbidity of this condition are relatively high, and early diagnosis and treatment may improve prognosis, which should await further investigation.