Glioblastoma multiform with primitive neuronal component, radiological and histology features: a case report

Background Glioblastoma multiform with primitive neuronal component (GBM-PNC) has been recently defined as a rare variant of glioblastoma multiform (GBM), which shows characteristically pathological pattern of less differentiated areas with small blue cell morphology and neuroectodermic immunophenotype. New studies emphasize its characteristics and differences, which have become vitally important due to the changes in therapeutic management. Case presentation We present the case of 57-year-old male patient who onset symptoms were secondarily widespread partial seizures and expression aphasia. Brain magnetic resonance imaging (MRI) reported left enhanced temporal infiltrating lesion, requiring surgery twice throughout two years. At first surgery, pathological samples revealed embryonic tumor of the central nervous system (grade IV, WHO 2016), so PACKER protocol consisting of CSRT (craniospinal radiation) plus weekly vincristine followed by 8 cycles of cisplatin, lomustine and vincristine usually used for medulloblastomas or other primitive neuroectodermal tumors was started. However, due to reappearance of symptoms and progression in MRI, reoperation was performed with definitive diagnosis of GBM-PNC (Grade IV, WHO 2016) and switched to STUPP protocol. Conclusions It is important to take into account the chance of this entity when histological, radiological and intraoperative findings orient toward a primitive neural tumor since the presence of GBM could be overlooked leading to mistakes in diagnosis and the therapeutic orientation.

Outcome Analysis and Prognostic Factors in Patients of Glioblastoma Multiforme: An Indonesian Single Institution Experience

Aims: This study was done to assess the survival of patients with glioblastoma multiform and to identify factors that can affect patient survival. Materials and methods: From January 2015 to December 2019, 55 patients with histopathologically confirmed glioblastoma multiform and received adjuvant radiation/chemoradiation in our department were retrospectively analyzed. Results: The median overall survival (OS) for entire cohort was 13 months and 1-year OS and 2-year OS rate were 52.7% and 3.6% with the mean follow-up period was 12 months. In univariate analysis, age (≤50 years vs >50 years, p=0.02), performance status (≥90 vs 70-80 vs <70, p<0.001), RTOG RPA classification (class III vs class IV vs class V-VI, p<0.001), parietal lobes tumor site (vs others, p=0.02), residual tumor volume (≤20.4cm3 vs >20.4cm3, p=0.001) and time to initiate adjuvant therapy (<4 weeks vs 4-6 weeks vs >6 weeks, p=0.01) were significantly affect overall survival. In multivariate analysis, RTOG RPA classification and involvement of parietal lobes were independent prognostic factors for overall survival. Conclusions: RTOG RPA classification that consisted of age and performance status is an independent prognostic factor for the clinical outcome of GBM. Besides this well-known factor, we also identified the involvement of parietal lobe gives a strong negative influence on survival of GBM patients.

Integrative Analyses and Verification of the Expression and Prognostic Significance for RCN1 in Glioblastoma Multiforme

Glioblastoma multiform is a lethal primary brain tumor derived from astrocytic, with a poor prognosis in adults. Reticulocalbin-1 (RCN1) is a calcium-binding protein, dysregulation of which contributes to tumorigenesis and progression in various cancers. The present study aimed to identify the impact of RCN1 on the outcomes of patients with Glioblastoma multiforme (GBM). The study applied two public databases to require RNA sequencing data of Glioblastoma multiform samples with clinical data for the construction of a training set and a validation set, respectively. We used bioinformatic analyses to determine that RCN1 could be an independent factor for the overall survival of Glioblastoma multiform patients. In the training set, the study constructed a predictive prognostic model based on the combination of RCN1 with various clinical parameters for overall survival at 0.5-, 1.0-, and 1.5-years, as well as developed a nomogram, which was further validated by validation set. Pathways analyses indicated that RCN1 was involved in KEAS and MYC pathways and apoptosis. In vitro experiments indicated that RCN1 promoted cell invasion of Glioblastoma multiform cells. These results illustrated the prognostic role of RCN1 for overall survival in Glioblastoma multiform patients, indicated the promotion of RCN1 in cell invasion, and suggested the probability of RCN1 as a potential targeted molecule for treatment in Glioblastoma multiform.

Different Recurrence and Growth Pattern of Gliomatous Foci after Mesenchymal Stem Cell Harbouring the Herpes Simplex Thymidine Kinase Gene Transplantation in Multifocal Glioblastoma Multiform: A Clinical Case Report

Background: Glioblastoma multiform (GBM) as a malignant brain tumor has poor prognosis despite the current therapies. Suicide gene therapy is one of the most widespread cancer gene therapies which requires mRNA encoding a pro-drug activating enzyme transduced into the vector such as Mesenchymal Stem Cells (MSCs) that injects into the tumor tissue and leads to tumor suppression. Case presentation: In this case report, the authors describe a 37-year-old man with two obvious foci of glioblastoma multiform at left frontal and left parietal lobes. After the resection of the foci, the patient received stem cell-mediated herpes simplex virus thymidine kinase (HSV-TK) gene at frontal focus of tumor besides ganciclovir as prodrug for 14 days after injection. Then he was followed up with regular magnetic resonance imaging (MRI). The growth and recurrence pattern of foci was assessed. After the injection on Feb 09, 2019, the patient’s follow-up revealed recurrence of parietal focus on Dec 19, 2019; however, frontal focus had a slight and unremarkable enhancement. Until our last radiological follow-up (on Mar 18, 2020) left frontal focus had no prominent recurrence and the size of the left parietal focus increased and extended to the contralateral hemisphere through the corpus callosum. Eventually patient has passed away on July 16, 2020 (PFS=293 days, OS=657 days).Conclusions: It seems that the gliomatous focus that undergone administration of bone marrow MSC containing the HSV-TK gene, had a different pattern of growth and recurrence compared to a non-treated one.

Analysis and Construction of ceRNA Networks Reveal 4 mRNAs as Potential Biomarkers of Temozolomide-resistant Glioblastomas

Background: Glioblastoma multiform (GBM) is the most malignant tumor of central nervous system. Although temozolomide (TMZ) was reported to improve the prognosis of GBM since applied to clinical practice, its chemoresistance has become a hot research focus and even been thought as the major factor of tumor recurrence. It’s urgent to illustrate the mechanism of TMZ resistance in GBM.Methods: In this study, we retrieved and analyzed expression profiles of TMZ resistant and TMZ sensitive glioma cell lines from GEO datasets, and then identified the enriched pathways of the differentially expressed genes. Moreover, genes involved in the KEGG pathways closely related to GBM from the Comparative Toxicogenomics 2020 Update Database were used for survival analysis of GBM samples from TCGA database. Finally, competing endogenous RNA networks regulating the acquired genes were constructed based on the expression profiles and public database. Results：To our knowledge, we firstly identified 4 mRNAs (LAMA1, COL5A1, ITGA2 and STK11) as potential biomarkers of TMZ resistant GBMs, then constructed their competing endogenous RNA networks. Conclusions: The results would provide theoretical basis for overcoming TMZ chemoresistance and contribute to more optimal chemotherapy of GBMs.