Browsing by Author "Raicevic, Savo (56176851100)"

Background Current treatment protocol for glioblastoma multiforme (GBM) is based on maximal safe resection followed by the Stupp protocol. In Serbia, temozolomide was introduced as adjuvant therapy in 2011. The aims of this study were to confirm the safety and efficacy on overall and progression-free survival of the Stupp protocol and evaluate the influence of prognostic factors in one of the largest series of patients with GBM treated over a 2-year period. Methods Between January 2010 and December 2012, 110 patients with newly diagnosed GBM underwent surgical removal at the Neurooncology Department of the Clinic Center of Serbia. Patients were divided into 2 groups according to postoperative treatment. Group A (n = 24 patients), treated before January 2011, received adjuvant standard radiation therapy and carmustine (bis-chloroethyl-nitrosourea), and group B (n = 86 patients), treated after January 2011, received postoperative treatment according to the Stupp protocol. Results The Stupp protocol had a significant favorable impact on overall survival at 1-year follow-up (79.1% in group B vs. 62.5% in group A; P = 0.016); no differences were noted in regard to progression-free survival. Multivariate analysis identified younger age and gross total resection of tumor as positive prognostic factors. Conclusions Adoption of the Stupp protocol had a favorable impact on overall, but not on progression-free, survival rate. Wider surgical resection involving the peritumoral brain zone, as confirmed by univariate and multivariate analysis, represents the most favorable prognostic factor. © 2017 Elsevier Inc.

Purpose: Intracranial collision tumor is a rare entity that represents the coexistence of two histopathological different tumor types in the same area without histological admixture or an intermediate cell population zone. So far, several cases of collision tumors with ganglioglioma as its component have been reported in the literature, while supratentorial ependymoma has never been reported as a collision tumor component. We are presenting a unique case of collision tumor in patient without previous history of head trauma, neurological surgery, radiotherapy, or phakomatosis. Methods and results: A 17-year-old male with no previous history of head trauma, neurological surgery, radiotherapy, or phakomatosis was presented to our clinic with grand mal seizure. Brain magnetic resonance imaging with gadolinium contrast was done revealing a contrast-enhancing lesion of right frontal lobe closely related to dura, surrounded by perifocal edema. The patient underwent a gross total tumor resection. Histological examination revealed collision tumor with two distinct components: ganglioglioma and supratentorial ependymoma. Conclusion: To our best knowledge, no previous reports of collision tumor composed of ganglioglioma and supratentorial ependymoma in a single patient have been reported. We believe that this report could significantly contribute to further surgical practice as well as to treatment decision for these types of collision tumors. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Background: Metastatic brain tumors are typically located at the cerebral hemispheres or the cerebellum and most frequently originate from primary breast or lung tumors. Metastatic lesions are usually associated with blood–brain barrier disruption, solid or ring-like contrast enhancement, and perilesional vasogenic edema on brain imaging. Even in cases where metastases are predominantly cystic, enhancement of the minor solid component can be detected. In contrast, non-enhancing secondary brain tumors were only reported in a patient after antiangiogenic treatment with bevacizumab. Case report: We report a case of a 54-year-old male who presented with left-sided weakness and multiple seizures. Brain magnetic resonance imaging revealed a T2-weighted heterogeneous solid tumor in the right frontoparietal parasagittal region, with no apparent enhancement on T1-weighted post-contrast images and no evident perilesional edema. Further MRS analysis revealed markedly increased choline and lipid peaks. The patient underwent craniotomy for tumor removal. Histopathology revealed findings consistent with metastatic non-microcellular neuroendocrine lung cancer. positron emission tomography/computed tomography (PET/CT) revealed a stellate lesion within the right upper lung lobe, compatible with primary lung cancer. Conclusion: Non-enhancing brain metastatic tumors are rarely reported in the literature, usually following antiangiogenic treatment. Here, we report the first ever case of a non-enhancing metastatic brain tumor with no prior history of antiangiogenic treatment, with particular emphasis on the importance of MRS analysis in atypical brain lesions. Copyright © 2022 Kozic, Lasica, Grujicic, Raicevic, Prvulovic Bunovic, Nosek and Boban.

Background: Metastatic brain tumors are typically located at the cerebral hemispheres or the cerebellum and most frequently originate from primary breast or lung tumors. Metastatic lesions are usually associated with blood–brain barrier disruption, solid or ring-like contrast enhancement, and perilesional vasogenic edema on brain imaging. Even in cases where metastases are predominantly cystic, enhancement of the minor solid component can be detected. In contrast, non-enhancing secondary brain tumors were only reported in a patient after antiangiogenic treatment with bevacizumab. Case report: We report a case of a 54-year-old male who presented with left-sided weakness and multiple seizures. Brain magnetic resonance imaging revealed a T2-weighted heterogeneous solid tumor in the right frontoparietal parasagittal region, with no apparent enhancement on T1-weighted post-contrast images and no evident perilesional edema. Further MRS analysis revealed markedly increased choline and lipid peaks. The patient underwent craniotomy for tumor removal. Histopathology revealed findings consistent with metastatic non-microcellular neuroendocrine lung cancer. positron emission tomography/computed tomography (PET/CT) revealed a stellate lesion within the right upper lung lobe, compatible with primary lung cancer. Conclusion: Non-enhancing brain metastatic tumors are rarely reported in the literature, usually following antiangiogenic treatment. Here, we report the first ever case of a non-enhancing metastatic brain tumor with no prior history of antiangiogenic treatment, with particular emphasis on the importance of MRS analysis in atypical brain lesions. Copyright © 2022 Kozic, Lasica, Grujicic, Raicevic, Prvulovic Bunovic, Nosek and Boban.

Background: Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurrence. Because ICG invades the hypothalamus and/or pituitary, endocrine dysfunction is one of the common determinants of these tumours. We present two brothers with a history of ICG. Patient 1 is a 25-year-old male who suffered from weakness of the right half of his body at the age of 18 years. Cranial MRI revealed a mass lesion in the left thalamus. He underwent neurosurgery, and the tumour was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumour after radiation therapy. At the age of 22 years a diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Molecular genetic analysis of the tumour tissue detected the mutation within exon 2 in KRAS gene. Patient 2 is a 20-year-old man who presented with diabetes insipidus at the age of 12 years. MRI detected tumour in the third ventricle and pineal region. After endoscopic tumour biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy and was treated with GH during childhood. At the age of 18 years GH replacement was reintroduced. A six-month follow-up during the subsequent two years in both brothers demonstrated the IGF1 normalisation with no MRI signs of tumour recurrence. Conclusion: To the best of our knowledge, so far only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside Japan. They have been treated successfully with GH therapy in adulthood. © 2018 Via Medica. All rights reserved.

Background: Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurrence. Because ICG invades the hypothalamus and/or pituitary, endocrine dysfunction is one of the common determinants of these tumours. We present two brothers with a history of ICG. Patient 1 is a 25-year-old male who suffered from weakness of the right half of his body at the age of 18 years. Cranial MRI revealed a mass lesion in the left thalamus. He underwent neurosurgery, and the tumour was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumour after radiation therapy. At the age of 22 years a diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Molecular genetic analysis of the tumour tissue detected the mutation within exon 2 in KRAS gene. Patient 2 is a 20-year-old man who presented with diabetes insipidus at the age of 12 years. MRI detected tumour in the third ventricle and pineal region. After endoscopic tumour biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy and was treated with GH during childhood. At the age of 18 years GH replacement was reintroduced. A six-month follow-up during the subsequent two years in both brothers demonstrated the IGF1 normalisation with no MRI signs of tumour recurrence. Conclusion: To the best of our knowledge, so far only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside Japan. They have been treated successfully with GH therapy in adulthood. © 2018 Via Medica. All rights reserved.

Introduction: Pituitary neuroendocrine tumours (PitNETs), traditionally designated as pituitary adenomas, show relatively frequent invasive growth with exceptional metastatic potential, the causes of which are not entirely elucidated. Kisspeptins, which perform their activity through KISS1 receptor (KISS1R), are recognised as metastatic suppressors in many malignant tumours. This study aimed to investigate the immunohistochemical expression of kisspeptin and KISS1R in different types of PitNETs and to compare it with the expression in the normal anterior pituitary, using tissue microarray. Material and methods: The experimental group consisted of 101 patients with PitNETs, with 45 (37.3%) being of gonadotroph, 40 (33.9%) somatotroph, 4 (3.4%) corticotroph, 4 (3.4%) thyrotroph, 3 (2.5%) lactotroph, and 6 (5.1%) null-cell type. The control group consisted of anterior pituitary tissue accidentally removed during the surgery for PitNETs in 17 patients. Results: Kisspeptin expression was observed in both experimental and control groups, without statistically significant differences in the staining intensity. Negative kisspeptin staining was detected in 10 (9.9%), weak in 79 (78.2%), and moderate in 12 tumours (11.9%); none of the tumours had strong staining intensity. The weak staining intensity was predominant in all PitNET types except thyrotroph tumours. Significant statistical difference in terms of kisspeptin expression between types of PitNET and the control group was not observed. Immunohistochemical expression of KISS1R was not observed in the control group or in the experimental group. Conclusions: We conclude that immunohistochemistry, as a method, cannot confirm the involvement of kisspeptin in tumourigenesis and aggressiveness of PitNETs, but potentially supports its antimetastatic role. The absence of KISS1R immunohistochemical expression in all anterior pituitaries and PitNETs in our cohort needs verification through the use of different procedures designed for the detection of the presence and localisation of proteins in the cell. (Endokrynol Pol 2021; 72 (2): 91-96). © 2021 Via Medica. All rights reserved.

Introduction: Pituitary neuroendocrine tumours (PitNETs), traditionally designated as pituitary adenomas, show relatively frequent invasive growth with exceptional metastatic potential, the causes of which are not entirely elucidated. Kisspeptins, which perform their activity through KISS1 receptor (KISS1R), are recognised as metastatic suppressors in many malignant tumours. This study aimed to investigate the immunohistochemical expression of kisspeptin and KISS1R in different types of PitNETs and to compare it with the expression in the normal anterior pituitary, using tissue microarray. Material and methods: The experimental group consisted of 101 patients with PitNETs, with 45 (37.3%) being of gonadotroph, 40 (33.9%) somatotroph, 4 (3.4%) corticotroph, 4 (3.4%) thyrotroph, 3 (2.5%) lactotroph, and 6 (5.1%) null-cell type. The control group consisted of anterior pituitary tissue accidentally removed during the surgery for PitNETs in 17 patients. Results: Kisspeptin expression was observed in both experimental and control groups, without statistically significant differences in the staining intensity. Negative kisspeptin staining was detected in 10 (9.9%), weak in 79 (78.2%), and moderate in 12 tumours (11.9%); none of the tumours had strong staining intensity. The weak staining intensity was predominant in all PitNET types except thyrotroph tumours. Significant statistical difference in terms of kisspeptin expression between types of PitNET and the control group was not observed. Immunohistochemical expression of KISS1R was not observed in the control group or in the experimental group. Conclusions: We conclude that immunohistochemistry, as a method, cannot confirm the involvement of kisspeptin in tumourigenesis and aggressiveness of PitNETs, but potentially supports its antimetastatic role. The absence of KISS1R immunohistochemical expression in all anterior pituitaries and PitNETs in our cohort needs verification through the use of different procedures designed for the detection of the presence and localisation of proteins in the cell. (Endokrynol Pol 2021; 72 (2): 91-96). © 2021 Via Medica. All rights reserved.

Normal pituitary tissue is frequently used for comparison with protein expression in tumor tissue, being obtained either at surgery or at autopsy. p16 and p21 proteins are cyclin-dependent kinase inhibitors, belonging to INK4 and Cip/Kip family, respectively. Their expression is increased in response to DNA damage or other cellular stressors, resulting in the activation of cell cycle checkpoints. They also play important roles in cellular senescence. The purpose of this study was to investigate differences in p16 and p21 immunohistochemical expression in normal pituitary tissue adjacent to pituitary adenoma obtained during neurosurgical procedure with pituitary tissue obtained at autopsy, from patients who died from non-endocrinological diseases. Our results show significant difference in p16 nuclear and p21 cytoplasmic immunohistochemical expression between two types of normal pituitary tissues. One of the reasons for this difference could be the age of subjects because those who underwent autopsy for a non-endocrinological disease were significantly older than subjects who underwent neurosurgery for a pituitary adenoma. Our finding that differences are probably not influenced by postmortem changes is supported by no significant correlation between postmortem interval and immunohistochemical p16 and p21 expression. The influence of the presence of a pituitary adenoma could not be evaluated in these specimens. © 2015, Springer Science+Business Media New York.

Normal pituitary tissue is frequently used for comparison with protein expression in tumor tissue, being obtained either at surgery or at autopsy. p16 and p21 proteins are cyclin-dependent kinase inhibitors, belonging to INK4 and Cip/Kip family, respectively. Their expression is increased in response to DNA damage or other cellular stressors, resulting in the activation of cell cycle checkpoints. They also play important roles in cellular senescence. The purpose of this study was to investigate differences in p16 and p21 immunohistochemical expression in normal pituitary tissue adjacent to pituitary adenoma obtained during neurosurgical procedure with pituitary tissue obtained at autopsy, from patients who died from non-endocrinological diseases. Our results show significant difference in p16 nuclear and p21 cytoplasmic immunohistochemical expression between two types of normal pituitary tissues. One of the reasons for this difference could be the age of subjects because those who underwent autopsy for a non-endocrinological disease were significantly older than subjects who underwent neurosurgery for a pituitary adenoma. Our finding that differences are probably not influenced by postmortem changes is supported by no significant correlation between postmortem interval and immunohistochemical p16 and p21 expression. The influence of the presence of a pituitary adenoma could not be evaluated in these specimens. © 2015, Springer Science+Business Media New York.

Background Primary intraventricular meningiomas (IVMs) make up 0.5%–5% of all intracranial meningiomas and represent one of the most challenging lesions in neurosurgery. Methods Between 1990 and 2013, 42 patients (30 female, 12 male; mean age, 43.6 years) underwent resection of their IVM. The removal was performed by a posterior parietal approach in 19 of the 40 lateral ventricle tumors, and 1 third ventricle meningioma. The transcallosal approach was used for 3 meningiomas, and patients with other lesions underwent temporal (7 cases) and temporoparietal approaches (12 patients), respectively. Results The most common presenting signs were increased intracranial pressure (83.3%), visual impairment (78.6%) and cognitive changes (50%). Forty lesions (95.2%) arose in the lateral ventricles, and 2 (4.8%) in the third ventricle, ranging in size from 3 to 10 cm. Total removal was achieved in 39 cases and the pathology report disclosed World Health Organization grade I lesions in 41 cases. Hydrocephalus, cerebrospinal fluid leakage, and cerebral edema were the postoperative complications (7.15%); 1 patient died of respiratory problems not directly related to surgery. Thirty-five patients (83.3%) showed a 6-month Glasgow Outcome Scale of 5. One patient, who underwent partial resection, presented a recurrence after 1 year that remained stable until last follow-up. Conclusions IVMs usually reach a large size before being diagnosed. Surgical treatment is the most suitable option and total removal should represent the main goal of the procedure. The posterior parietal transulcal approach and the temporoparietal approach are the most common surgical routes used in our series. © 2016

Purpose: The aim of this study was to present the management and treatment of children with medulloblastoma in Serbia, a middle-income country (MIC). Methods: The data of 87 children diagnosed with medulloblastoma and treated at the Institute for Oncology and Radiology of Serbia from 2000 to 2013 were analyzed. Results: The children’s median age was 8.3 years (range 2.5-17.3). Eighty-two (94.2%) were 3 years or older. Sixty-two (71.3%) patients had stage M0 medulloblastoma, 12 (13.8%) had stage M1 and 13 (14.9%) had stage M2 or M3. As of October 2015, 51 (58.6%) patients were alive and 31 (35.6%) had died. Five patients (5.7%) were lost to followup. Twenty-six patients relapsed. The median follow-up time was 58 months (range 4–187). Mean overall survival (OS) was 76.4% at 3 years, 66.2% at 5 years and 59.2% at 10 years. Mean disease-free survival (DFS) was 75.8% at 3 years, 62.8% at 5 years and 56.6% at 10 years. Mean OS of stage M0 patients was 86.4% at 3 years, 74% at 5 years and 63.1% at 10 years. The OS of stage M1, M2 and M3 patients combined was 48.9% at 3 years, 44.0% at 5 years and 37.7% at 10 years. Conclusion: In Serbia, a MIC, it is possible to achieve good treatment results in children with medulloblastoma using international treatment guidelines and recommendations, available resources and an experienced team of professionals dedicated to pediatric neurooncology. © 2018 Zerbinis Publications. All Rights Reserved.

Purpose: The aim of this study was to present the management and treatment of children with medulloblastoma in Serbia, a middle-income country (MIC). Methods: The data of 87 children diagnosed with medulloblastoma and treated at the Institute for Oncology and Radiology of Serbia from 2000 to 2013 were analyzed. Results: The children’s median age was 8.3 years (range 2.5-17.3). Eighty-two (94.2%) were 3 years or older. Sixty-two (71.3%) patients had stage M0 medulloblastoma, 12 (13.8%) had stage M1 and 13 (14.9%) had stage M2 or M3. As of October 2015, 51 (58.6%) patients were alive and 31 (35.6%) had died. Five patients (5.7%) were lost to followup. Twenty-six patients relapsed. The median follow-up time was 58 months (range 4–187). Mean overall survival (OS) was 76.4% at 3 years, 66.2% at 5 years and 59.2% at 10 years. Mean disease-free survival (DFS) was 75.8% at 3 years, 62.8% at 5 years and 56.6% at 10 years. Mean OS of stage M0 patients was 86.4% at 3 years, 74% at 5 years and 63.1% at 10 years. The OS of stage M1, M2 and M3 patients combined was 48.9% at 3 years, 44.0% at 5 years and 37.7% at 10 years. Conclusion: In Serbia, a MIC, it is possible to achieve good treatment results in children with medulloblastoma using international treatment guidelines and recommendations, available resources and an experienced team of professionals dedicated to pediatric neurooncology. © 2018 Zerbinis Publications. All Rights Reserved.

Background and Objective Patients with presumed nonlesional focal epilepsy - based on either MRI or histopathologic findings - have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. Methods We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. Results Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings - versus nonspecific reactive gliosis - (AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. Discussion This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery - even more if the hippocampus is resected - compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways. © American Academy of Neurology.

Objectives: Spinal glioblastomas represent a rare entity accounting for ca 1–3% of all intramedullary tumors; data about survival, prognostic factors and therapeutic protocols are quite poor. Even with an aggressive multimodal management the spinal glioblastoma patients’ survival remains poor, with rapid progression of the disease. This study reports our experience with the management of the primary intramedullary glioblastomas, also in regard to the current literature data. Patients and Methods: We retrospectively analyzed the medical records of 5 patients treated at the Department for Neuro-oncology and Spine Surgery of the Clinical Center of Belgrade, Serbia, between January 2007 and December 2016 for a primary intramedullary glioblastoma. Demographic characteristics, pre-operative data and post-operative results were then compared with previous literature regarding spinal GBMs and attempt to identify potential prognostic factors. Results: Gross total resection was achieved in two patients, while a subtotal resection was performed in the latter 3 cases; as per protocol, all patients underwent to surgery, followed by radio and chemotherapy. There were no intraoperative complications and no patients developed a new postoperative neurological defect; the median overall survival was 6 months. Progression or recurrence of disease was noted in all patients at the 3-months follow-up, despite the adjuvant treatments. Conclusions: To the date, there is a lack of consensus on specific management of spinal glioblastomas: the extent of resection can play an important role, but it appears to be not preeminent. A shorter interval between symptoms onset and treatment and a smaller extension of the tumor seem to be correlated with better outcomes and a longer overall survival. However, there is not an adjunctive viable standardized postoperative therapy yet, which results in concrete and persistent improvement of overall survival and progression free survival. © 2021 The Authors

Glioblastomas are aggressive and usually incurable high-grade gliomas without adequate treatment. In this study, we aimed to investigate the potential of desloratadine to induce apoptosis/autophagy as genetically regulated processes that can seal cancer cell fates. All experiments were performed on U251 human glioblastoma cell line and primary human glioblastoma cell culture. Cytotoxic effect of desloratadine was investigated using MTT and CV assays, while oxidative stress, apoptosis, and autophagy were detected by flow cytometry and immunoblot. Desloratadine treatment decreased cell viability of U251 human glioblastoma cell line and primary human glioblastoma cell culture (IC50 value 50 µM) by an increase of intracellular reactive oxygen species and caspase activity. Also, desloratadine decreased the expression of main autophagy repressor mTOR and its upstream activator Akt and increased the expression of AMPK. Desloratadine exerted dual cytotoxic effect inducing both apoptosis- and mTOR/AMPK-dependent cytotoxic autophagy in glioblastoma cells and primary glioblastoma cell culture. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Glioblastomas are aggressive and usually incurable high-grade gliomas without adequate treatment. In this study, we aimed to investigate the potential of desloratadine to induce apoptosis/autophagy as genetically regulated processes that can seal cancer cell fates. All experiments were performed on U251 human glioblastoma cell line and primary human glioblastoma cell culture. Cytotoxic effect of desloratadine was investigated using MTT and CV assays, while oxidative stress, apoptosis, and autophagy were detected by flow cytometry and immunoblot. Desloratadine treatment decreased cell viability of U251 human glioblastoma cell line and primary human glioblastoma cell culture (IC50 value 50 µM) by an increase of intracellular reactive oxygen species and caspase activity. Also, desloratadine decreased the expression of main autophagy repressor mTOR and its upstream activator Akt and increased the expression of AMPK. Desloratadine exerted dual cytotoxic effect inducing both apoptosis- and mTOR/AMPK-dependent cytotoxic autophagy in glioblastoma cells and primary glioblastoma cell culture. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Purpose: Glioblastoma is the most common and lethal adult brain tumor. Despite current therapeutic strategies, including surgery, radiation and chemotherapy, the median survival of glioblastoma patients is 15 months. The development of this tumor depends on a sub-population of glioblastoma stem cells governing tumor propagation and therapy resistance. SOX3 plays a role in both normal neural development and carcinogenesis. However, little is known about its role in glioblastoma. Thus, the aim of this work was to elucidate the role of SOX3 in glioblastoma. Methods: SOX3 expression was assessed using real-time quantitative PCR (RT-qPCR), Western blotting and immunohistochemistry. MTT, immunocytochemistry and Transwell assays were used to evaluate the effects of exogenous SOX3 overexpression on the viability, proliferation, migration and invasion of glioblastoma cells, respectively. The expression of Hedgehog signaling pathway components and autophagy markers was assessed using RT-qPCR and Western blot analyses, respectively. Results: Higher levels of SOX3 expression were detected in a subset of primary glioblastoma samples compared to those in non-tumoral brain tissues. Exogenous overexpression of this gene was found to increase the proliferation, viability, migration and invasion of glioblastoma cells. We also found that SOX3 up-regulation was accompanied by an enhanced activity of the Hedgehog signaling pathway and by suppression of autophagy in glioblastoma cells. Additionally, we found that SOX3 expression was elevated in patient-derived glioblastoma stem cells, as well as in oncospheres derived from glioblastoma cell lines, compared to their differentiated counterparts, implying that SOX3 expression is associated with the undifferentiated state of glioblastoma cells. Conclusion: From our data we conclude that SOX3 can promote the malignant behavior of glioblastoma cells. © 2018, International Society for Cellular Oncology.

Purpose: Glioblastoma is the most common and lethal adult brain tumor. Despite current therapeutic strategies, including surgery, radiation and chemotherapy, the median survival of glioblastoma patients is 15 months. The development of this tumor depends on a sub-population of glioblastoma stem cells governing tumor propagation and therapy resistance. SOX3 plays a role in both normal neural development and carcinogenesis. However, little is known about its role in glioblastoma. Thus, the aim of this work was to elucidate the role of SOX3 in glioblastoma. Methods: SOX3 expression was assessed using real-time quantitative PCR (RT-qPCR), Western blotting and immunohistochemistry. MTT, immunocytochemistry and Transwell assays were used to evaluate the effects of exogenous SOX3 overexpression on the viability, proliferation, migration and invasion of glioblastoma cells, respectively. The expression of Hedgehog signaling pathway components and autophagy markers was assessed using RT-qPCR and Western blot analyses, respectively. Results: Higher levels of SOX3 expression were detected in a subset of primary glioblastoma samples compared to those in non-tumoral brain tissues. Exogenous overexpression of this gene was found to increase the proliferation, viability, migration and invasion of glioblastoma cells. We also found that SOX3 up-regulation was accompanied by an enhanced activity of the Hedgehog signaling pathway and by suppression of autophagy in glioblastoma cells. Additionally, we found that SOX3 expression was elevated in patient-derived glioblastoma stem cells, as well as in oncospheres derived from glioblastoma cell lines, compared to their differentiated counterparts, implying that SOX3 expression is associated with the undifferentiated state of glioblastoma cells. Conclusion: From our data we conclude that SOX3 can promote the malignant behavior of glioblastoma cells. © 2018, International Society for Cellular Oncology.