bluuebunny/crossref_metadata_2025_split huggingface dataset:
P07.02 Enhanced glycolysis in glioblastomas is associated with tumor cells migration
Authors: Ndiaye M , Rébé C , Ilie A , Ménégaut L , Pilot T , Ghiringhelli F 
Published: September 2019

Abstract

BACKGROUND
Glioblastoma is the most common primary brain tumor. Its prognosis remains poor even with the standard treatment - the Stupp protocol.The classic Warburg effect in cancers leads to increased glycolysis which causes acidification of the tumor environment. This phenomenon may favor migration of tumor cells as already reported in pancreatic ductal adenocarcinoma. We therefore hypothesized that enhanced glycolysis in glioblastomas could favor the tumor cell migration.

MATERIAL AND METHODS
We measured glycolysis by the extracellular acidification rate (ECAR) of several human glioblastomas cell lines (LN229, LN18, T98-G, U87-MG, U373-MG, U118-MG) with the Seahorse Analyzer. To confirm these results, we also measured the intracellular cAMP rates using the Cayman’s Elisa kit and we analyzed by RT-PCR the expression of the main genes coding for enzymes involved in glycolysis in these glioblastomas cell lines. Cell migration was measured with a scratch wound healing assay during 24 hours.

RESULTS
U118-MG was the glioblastoma cell line with the highest glycolysis rate, the highest production of cAMP and showed a strong expression of glycolysis-associated genes. LN229 was the glioblastoma cell line with the less important glycolysis rate, the lower production of cAMP and showed a weaker expression of glycolysis-associated genes. According to the scratch wound healing assay, U118-MG cells showed a more important migration than LN229 cells at 24 hours.

CONCLUSION
Glycolysis may be an attractive target to prevent effectively tumor cell migration in glioblastomas. Coupling the evaluation of glycolysis with histomolecular characterization of glioblastomas, could help to identify patients to whom adjuvant therapies that inhibit glycolysis such as fenofibrate could be proposed.
P09.02 Surgical treatment for intracranial meningiomas in elderly patients growing during follow-up study
Authors: Okuma M 
Published: September 2019

Abstract

BACKGROUND
In Japan in which life expectancy exceeds 85 years old, there are many elderly people who have sufficient healthy life even over 75 years of age and maintain social activities. With the increase in life expectancy and widespread use of magnetic resonance imaging (MRI), it is estimated that the number of asymptomatic meningioma diagnosed in elderly patients will increase. They are often followed up for the elderly, but they often become symptomatic as the tumor grows. Considering the inherent complications of the elderly and the patient’s life expectancy, it is often difficult to decide whether to operate. Here, we report the results of surgical treatment for intracranial meningiomas in elderly patients growing during follow-up study.

MATERIAL AND METHODS
Between January 2010 and December 2018, we treated 322 meningioma patients, including 18 patients older than 75 years old who had grown during follow-up. We performed a retrospective analysis of the 18 patients and measured Tumor doubling time (TDT) using CT scan or MRI image. We mainly examined the relationship between TDT and WHO classification, MIB-1 index, edema and calcification, intensity on MRI T2 weighted-imaging.

RESULTS
5 were male and 13 were female. There were 6 cases of skull base meningioma and 13 cases in which the tumor showed high intensity on the MRI T2 weighted-imaging. 4 cases showed intratumoral hemorrhage. 8 cases had edema. 11 cases were symptomatic meningiomas and 7 cases were asymptomatic meningiomas. There were 7 cases of WHO grade I meningioma and 11 cases of WHO grade II or III meningiomas. TDT was an average of 1.82 year (0.37–3.74). 9 patients have taken anticoagulant or antiplatelet medication.

CONCLUSION
In following up elderly meningioma patients, MRI should be performed at periodic intervals if the tumor showed high intensity on the MRI T2 weighted-imaging or had edema. In case of surgical treatment, we should pay attention to taking anticoagulant or antiplatelet medication, and treatment strategy is needed to avoid complications with sufficiently preoperative examination.
P09.03 Array-CGH analysis in meningiomas adds further information of biological behavior
Authors: Calatozzolo C , Rizzo A , Girgenti V , Saladino A , Patanè M , Di Meco F , Pollo B , Sciacca F L 
Published: September 2019

Abstract

BACKGROUND
Meningioma is the most common primary tumor of CNS, usually a benign tumor (grade I) successfully treated by surgical resection, while in the 25–30% of cases is a more aggressive neoplasm with high recurrence rate and poor prognosis (grade II-III). In the last years some studies tried to investigate the genomic profile of meningioma to find additional prognostic factors and potential therapeutic targets. Aim of our study was to use the array-CGH (aCGH) to investigate possible indicators of recurrence risk in meningiomas.

MATERIAL AND METHODS
We retrospectively selected two group of patients: 34 with meningioma WHO grade I (24 F, 10 M, median age at diagnosis 56 yrs) and 19 with meningioma WHO grade II (9 F, 10 M, median age 59 yrs), in order to compare cases recurrent and non-recurrent in each group. We also analyzed 5/18 recurrences WHO grade I and 10/11 WHO grade II. Genomic profiles were investigated by aCGH.

RESULTS
We observed an increase in number of genomic imbalances related to grading and in non-recurrent versus recurrent tumors. 9 WHO I meningiomas were without alterations. The mainly alterations observed were deletions and duplications, moreover we also identified chromothripsis of a single chromosome in 2/18 WHO I recurrent and 2/8 WHO II non recurrent meningiomas, and chromothripsis of multiple chromosomes in 5/11 WHO II recurrent meningiomas. As well we detected the presence of mosaicism, mainly in WHO I recurrent and in grade II meningiomas. In 7/14 WHO I meningiomas we found differences in genomic profile analyzing two samples obtained from two distinct areas. 6/15 recurrences showed the same alterations of the primary tumor. We didn’t detected an association between alteration of 1p and 22q and recurrence risk, as previously suggested, as those were the most diffused imbalances in all meningiomas.

CONCLUSION
In our patients we found a difference in genomic imbalances between grade I and grade II meningiomas, but we also identified additional details of the complexity of alterations in meningioma with the detection of chromothripsis and mosaicism. This latter aspect is a new issue and suggests the presence of more aggressive cell clones that could be predictive of recurrence in grade I meningioma. Moreover, we observed a spatial heterogeneity in half of grade I meningioma analyzed. Our preliminary results suggest that the aCGH, a technique routinely used in many laboratories, could be used to better stratify meningioma patients.
P09.07 Constitutive activation of the EGFR-STAT1 axis increases proliferation of meningioma tumour cells
Authors: Hanemann C O , Ferluga S , Baiz D , Sharma V , Adams C L , Bassiri K , Dunn J , Ercolano E , Kurian K , Hilton D A 
Published: September 2019

Abstract

BACKGROUND
Meningiomas are the most frequent primary brain tumours of the central nervous system. The standard of treatment is (radio)surgery, but the lack of knowledge of their tumorigenesis contributes to delay the development of additional therapeutic options.

MATERIAL AND METHODS
We used a variety of differen model systems and cell biology techniques

RESULTS
We found STAT1 widely overexpressed in meningioma tumours and in patient-derived meningioma cells but not in the corresponding healthy controls. The protein showed a constitutive phosphorylation on both phosphosites (Y701 and S727), which was not dependent on the JAK/STAT pathway. STAT1 knocked down resulted in a significant reduction of cellular proliferation, showed as a decrease in Ki67-positive cells and Cyclin D1, and deactivation of AKT and ERK 1/2. By studying STAT1 binding partners we isolated a complex composed by STAT1, STAT2, PRMT5 and MEP50. As PRMT5 is known to interact with EGFR, we tested the tyrosine kinase and found that EGFR was constitutively active in meningioma and was responsible for the aberrant phosphorylation of STAT1 on both phosphosites. We tested different drugs inhibiting of EGFR phosphorylation, Canertinib was most effective. It caused a significant reduction in meningioma cells proliferation and a reduction of overall levels of Cyclin D1, phospho- AKT and phospho-ERK 1/2. Hence, STAT1 constitutive phosphorylation, initiated by EGFR activation, is responsible for inducing a positive feedback loop causing its own overexpression and consequently an increased proliferation of the tumour cells.

CONCLUSION
These findings underline a pivotal role of the EGFR and STAT1 axis in meningioma and provides the rationale for further studies aiming to identify novel and effective therapeutic options.
P10.01 Anti-migration and anti-invasion effects of curcumin via suppression of fascin expression in glioblastoma cells
Authors: Ki-Su P , Yoon S , Hwang J , Ahn H 
Published: September 2019

Abstract

BACKGROUND
The natural compound Curcumin was known to inhibit migration and invasion of glioblastoma (GBM) cells. Fascin, a kind of actin-binding proteins, is correlated with migration and invasion of GBM cells. The purpose of this study was to investigate anti-migration and anti-invasion effects of Curcumin via suppression of fascin expression in GBM cells.

MATERIAL AND METHODS
U87 cell line was used as an experimental model of GBM. Fascin was quantified by Western blot analysis. And, the signal transducer and activator of transcription 3 (STAT3), known to play an important role in migration and invasion of tumor cells, were analyzed by sandwich-ELISA. Migration and invasion capacities were assessed by attachment, migration and invasion assays. Cellular morphology was demonstrated by immunofluorescence.

RESULTS
At various concentrations of curcumin and exposure times, fascin expression decreased. After temporarily exposure to 10μM/L Curcumin during 6 hours as less invasive concentration and time, fascin expression temporarily decreased at 12 hours (18.4%, p=0.024), and since then recovered. And, the change of phosphrylated STAT3 level also reflected the temporarily decreased pattern of fascin expression at 12 hours (19.7%, p=0.010). Attachment, migration, and invasion capacities consistently decreased at 6, 12, and 24 hours. And, immunofluorescence showed the change of shape and the reduction of filopodia formation in cells.

CONCLUSION
Curcumin is likely to suppress the fascin expression in GBM cells, and this might be a possible mechanism for anti-migration and anti-invasion effects of Curcumin via inhibition of STAT3 phosphorylation.
P10.06 Stiff limb syndrome associated to anti NMDA-R antibodies
Authors: Birzu C , Jaume L , Rostomashvilli S , Honnorat J , Berzero G , Psimaras D 
Published: September 2019

Abstract

BACKGROUND
Stiff person spectrum disorder is a group of rare conditions clinically characterized by the core symptoms of fluctuating muscular stiffness with superimposed spasms and an exaggerated startle response (hyperkplexia). It includes multiple variants amongst which are focal forms like stiff limb syndrome. Up to date, it was described in association with a spectrum of antibodies interfering with gabaergic transmission, most frequently antibodies targeting GAD, glycine receptor, amphiphysin and more rare dipeptidylpeptidase like protein 6, gephyrin, GABAAR and Glycine transporter 2.

MATERIAL AND METHODS
We report the case of a stiff limb syndrome associated to anti-NMDAR antibodies. The patient, a French 44-year male, with no antecedents presents with a 2-month history of painful spasms in his both legs resulting in a difficulty of walking and multiple falls. The diagnosis was supported by a stiff limb syndrome clinical pattern, a clinical response to treatment with benzodiazepines and baclofen and by the absence of other neurological finding that could have suggested an alternative diagnosis.

RESULTS
Anti NMDA-R antibodies were identified in blood and CSF samples using both immunofluorescence and cell-based assay. Any other intracellular and surface antibodies were negatives, GAD-ab included. Oncological evaluation was negative. The patient didn’t present encephalopathy signs and neuropsychological evaluation was normal. The patient received immunotherapy with one cure of intravenous immunoglobulins after an only partial improvement with symptomatic treatment.

CONCLUSION
This is the first case report of an association between the anti NMDA-R and stiff limb syndrome. Further investigations are needed to provide a better understanding of the pathophysiology of stiff person spectrum disorders.
P11.01 TMZ-LEV- IFN cocktail regimen significantly inhibited the growth of glioma
Authors: Ni X , Qu Y , Wang J , Chen F , Cai H , Yu Y , Yu Y , Yu Z , Cen Z , Chen Z 
Published: September 2019

Abstract

BACKGROUND
TMZ, is the first line chemotherapeutic drug for glioma, and drug resistance is one of the most important reasons for glioma treatment failure. Our previous studies have found that: 1) Type I interferon (IFN) could reverse the resistance of TMZ by inhibiting NF-κB activity, and down-regulating the expression of MGMT in vivo and in vitro; 2) IFN-α could significantly improve chemtherapeautic effect of TMZ for GBM patients. We aim to investigate the therapeutic effect of a cocktail chemotherapy regimen combining temozolomide (TMZ)- Levetiracetam(LEV) - interferon (IFN) on human glioma U138 and U251 subcutaneous xenograft tumor.

MATERIAL AND METHODS
30 xenograft tumors were established by subcutaneously injecting 1×106 glioma cells into the right flank of 4-week-old female BALB/C nude mice and then randomly divided into 5 groups (n=6/group): Control group; TMZ group; TMZ+IFN group; TMZ+LEV group; TMZ+LEV+IFN group. Anti-tumor efficacy of five regimens for tumor-bearing mice was tested after treatment with TMZ (50 mg/kg, i.p.), IFN (2×105 IU, s.c.), LEV (150 mg/kg, i.p.), while TMZ dose were reduced to 12.5 mg/kg for U251 tumors. All drugs are given once a day for five consecutive days. After therapy, the size of tumor was measured every day until the control tumors reached 2000 mm3. Mice bearing U138 tumors were sacrificed at 40 days after therapy, and mice bearing U251 tumors were killed at 26 days after therapy.

RESULTS
We identified that both U138 and U251 tumor growth among TMZ group, TMZ+IFN group, TMZ+LEV group and TMZ+LEV+IFN group were significantly inhibited (P<0.05), compared with the control group. Tumor weight of all treating group was lower than that of the control group (P<0.05). The tumor weight of TMZ+LEV+IFN group was the lowest and significantly lower than that of TMZ+LEV group and TMZ group (P<0.05, respectively). No significant difference was found between TMZ+LEV+IFN group and TMZ+IFN group in U251 subcutaneous xenograft tumors, although the tumor weight was lower in TMZ+LEV+IFN group (P>0.05). In the treatment of mice bearing U138 glioma, TMZ+LEV+IFN regimen was significantly superior to TMZ+IFN regimen.

CONCLUSION
Our data demonstrate that both IFN and LEV can sensitize TMZ effect on glioma. TMZ-LEV-IFN cocktail appears the best regimen.
P11.02 Hypothermia effect on glioblastoma cell viability, proliferation and migration
Authors: Fulbert C , Gaude C , Sulpice E , Chabardès S , Ratel D 
Published: September 2019

Abstract

BACKGROUND
Glioblastoma is the most common and aggressive primary brain tumor in adults. In spite of intensive treatment, patients have a poor prognosis with a median survival of 14–16 months. After surgical resection followed by postoperative chemoradiation (combined temozolomide treatment and radiotherapy), tumor recurs in the resection margin for more than 90% of patients. This recurrence results from the activation of residual glioblastoma cells beyond the resection cavity by therapy-induced injuries. To handle this issue, we propose therapeutic hypothermia as an adjuvant treatment, in order to place the resection margin in a state of hibernation. In fact, hypothermia was introduced as a promising therapeutic approach in various medical applications like cardiac arrest and pharmaco-resistant epilepsy. Only a few in vitro studies explored the effects of hypothermia on cancer cells and showed promising results. The aim of our work is to investigate the effects of hypothermia on glioblastoma cell proliferation and migration, two key cellular processes involved in cancer progression.

MATERIAL AND METHODS
We performed in vitro experiments on glioblastoma cell lines with different p53 status and various growth rates. For exploring the therapeutic potential of both mild and moderate hypothermia, we studied their impact on cell viability, proliferation and migration. We also performed cell cycle analysis by quantitation of DNA content using flow cytometry.

RESULTS
Results were similar for all glioblastoma cell lines, and demonstrated that cells were extremely sensitive to hypothermia. We showed that both mild and moderate hypothermia induced significant changes on glioblastoma cell lines behavior with a strong inhibition of cell proliferation and migration. Moderate hypothermia also affected glioblastoma cell viability and modified their distribution into the cell cycle phases.

CONCLUSION
Our results were comparable in all glioblastoma cell lines tested, demonstrating a consistent and universal effect of hypothermia. We showed that hypothermia significantly inhibits cell proliferation and migration, which are key processes involved in tumor growth. Proliferation arrest could be explained by the accumulation of cells in the G2/M phase of the cell cycle.
Together, these results support hypothermia as a promising adjuvant therapy for glioblastoma patients. Indeed, combined with current treatments, moderate hypothermia applied at the resection margin could prevent tumor recurrence after surgical resection. There is a crucial need to propose innovative glioblastoma treatments, and hypothermia appears as a promising therapeutic way.

SUPPORT
This work received financial support through grants from the Groupement des Entreprises Françaises de Lutte contre le Cancer (GEFLUC Grenoble - Dauphiné - Savoie) and the Fonds de dotation Clinatec.
P11.16 The stemness andinvasiveness of glioblastoma tumorspheres were suppressed by combined treatment with2’-hydroxycinnamaldehyde andtemozolomide
Authors: Kim W 
Published: September 2019

Abstract

BACKGROUND
Glioblastoma (GBM) is the most common and aggressive human primary brain malignancy. The key properties of GBM, stemness and invasiveness, are known to be associated with a highly unfavorable prognosis. Notably, the process of epithelial-mesenchymal transition (EMT) is closely related to the progression of GBM. On the basis of reports that 2′-hydroxycinnamaldehyde (HCA) and its derivative, 2′-benzoyloxycinnamaldehyde (BCA), suppresses EMT in several human cancer cells, we sought to evaluate the therapeutic efficacy of HCA and BCA, alone and in combination with temozolomide (TMZ), on GBM tumorspheres (TSs).

MATERIAL AND METHODS
Two human GBM TSs were treated with HCA, BCA, or TMZ. Therapeutic effects were evaluated by measuring ATP levels, neurosphere formation, 3D-invasion in collagen matrix, and viability. Protein expression profiles after drug treatment were evaluated by western blotting. In vivo anticancer efficacy of drugs was examined in a mouse orthotopic xenograft model.

RESULTS
Combined treatment of GBM TSs with HCA or BCA and TMZ significantly reduced cell viability, stemness, and invasiveness. Expression levels of stemness-, invasiveness-, and mesenchymal transition-associated markers, Zeb1, N-cadherin, and β-catenin, were also substantially decreased by the combined treatment. The combined treatment also reduced tumor growth in a mouse orthotopic xenograft model.

CONCLUSION
Our findings suggest that HCA and BCA, combined with TMZ, are potential therapeutic agents in the treatment of GBM.
P11.18 Tumor treating fields (TTFields) treatment of spinal cord metastases
Authors: Kinzel A , Yesharim O , Naveh A , Bomzon Z 
Published: September 2019

Abstract

BACKGROUND
Tumor Treating Fields (TTFields) is an anti-mitotic cancer treatment approved for the treatment of Glioblastoma multiforme (GBM) and is currently also investigated in a phase III trial in 1–10 brain metastases from non-small cell lung cancer (METIS). Apart from spread to the brain, some cancer types, such as breast cancer, lung cancer, and melanoma, may lead to metastatic spread to the spinal cord. Previous studies have shown that reported transducer array layouts for the treatment of abdominal/pelvic tumors (e.g. pancreatic cancer), with one pair of arrays positioned on the anterior and posterior of the patient, and the second pair of arrays placed on each side of the thorax, yield therapeutically insufficient field intensities of <1 V/cm in the spinal cord. This finding probably results from the anatomical structure of the spine, consisting of the cerebrospinal fluid as a highly conductive layer, encased by a resistive bone structure that shunts the current delivered across the body by the arrays away from the spine. This simulation-based study aimed at resolving this challenge by identifying novel array layouts on the body that effectively deliver TTFields to the spine.

MATERIAL AND METHODS
For the simulations of the TTFields delivery to the spine, a human male 34 years old realistic computational model (DUKE v3.1 by ITI’S, Zurich) and the ZMT’s Sim4Life v4.0 electro-quasi-static solver was utilized. TTFields were simulated by imposing an alternating current with a current density of 200 mA/disk and a frequency of 150 kHz on the outer surfaces of the disks of each pair of arrays.

RESULTS
For one of the tested array layouts, a high electric field was shown to be induced within the spinal cord and surrounding CSF: Our calculations of mean field intensity within the spine and nerves from vertebrae T8-T9 at the top to L3-L4 at the bottom added up to 1.77 V/cm. This layout consisted of the placement of a pair of arrays on the back of the patient, with one array positioned above the section in the spine to which treatment would be delivered, and the other array positioned below the target section. Notably, the resulting electric field is directed along the spine in this setting (ie, vertically).

CONCLUSION
Our results demonstrate that treatment of the whole spinal cord and nerves in a single direction can be achieved by placing a pair of transducer arrays on the patient’s back: one array on the neck, and one at the bottom of the spine. For the development of an active treatment in the perpendicular direction, further studies need to be conducted.