scholarly journals TB-9 An attempt to establish a patient-derived brain tumor culture model by organoid culture method

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi7-vi7
Author(s):  
Hideki Kuroda ◽  
Noriyuki Kijima ◽  
Tomoyoshi Nakagawa ◽  
Ryuichi Hirayama ◽  
Yoshiko Okita ◽  
...  

Abstract Background: Molecular heterogeneity among and within tumors are one of the reasons for the poor survival rate of brain tumors even with the current standard therapy. However, monolayer culture and neuro-sphere culture (NS) use exogenous growth factors, so may not show the true nature of the tumor. And the culture establishment rate is low, especially low-grade tumors. Therefore, we used the glioblastoma organoid (GBO) culture method showed by Fadi to create culture models of various brain tumors and investigated their characteristics. Methods: We examined the establishment rate in pathological and genotypic types of 56 patients who underwent brain tumor resection at our hospital between January 2020 and June 2021 and were cultured with GBO or NS. If tumor cells are increased visually at 1 month after culture, we defined establishment. Results: There were 15 cases of glioblastoma, 7 cases of anaplastic astrocytoma, 7 cases of diffuse astrocytoma, 3 cases of diffuse midline glioma, 2 cases of anaplastic oligodendroglioma, 5 cases of oligodendroglioma, and 16 cases of others. The establishment rate was 76.5% by the GBO method and 40% by the N S method. By histological type, GBO: 80% in glioblastoma, NS: 58.3% in glioblastoma, GBO: 83.3% in AA, NS: 40% in AA, and GBO: 100% in DA. The IDH mutation and pTERT mutation were investigated in GBO: IDHwt/TERT+ 87.5%, IDHwt/TERT- 64.3%, IDHmt/TERT- 100%, and in NS: IDHwt/TERT+ 75%, IDHwt/TERT- 33.3%, IDHmt/ TERT- 20% in NS. In addition, establishment was observed in GBO 2 case in medulloblastoma, 1 case in ependymoma. Discussion and Conclusion: This suggest that GBO can be used to establish culture models for low-grade tumors. In addition, GBO can establish culture earlier, so it is expected to be applicable to personalized therapies such as preclinical drug efficacy studies tailored to individual patients.

2022 ◽  
Vol 22 (1) ◽  
pp. 1-30
Author(s):  
Rahul Kumar ◽  
Ankur Gupta ◽  
Harkirat Singh Arora ◽  
Balasubramanian Raman

Brain tumors are one of the critical malignant neurological cancers with the highest number of deaths and injuries worldwide. They are categorized into two major classes, high-grade glioma (HGG) and low-grade glioma (LGG), with HGG being more aggressive and malignant, whereas LGG tumors are less aggressive, but if left untreated, they get converted to HGG. Thus, the classification of brain tumors into the corresponding grade is a crucial task, especially for making decisions related to treatment. Motivated by the importance of such critical threats to humans, we propose a novel framework for brain tumor classification using discrete wavelet transform-based fusion of MRI sequences and Radiomics feature extraction. We utilized the Brain Tumor Segmentation 2018 challenge training dataset for the performance evaluation of our approach, and we extract features from three regions of interest derived using a combination of several tumor regions. We used wrapper method-based feature selection techniques for selecting a significant set of features and utilize various machine learning classifiers, Random Forest, Decision Tree, and Extra Randomized Tree for training the model. For proper validation of our approach, we adopt the five-fold cross-validation technique. We achieved state-of-the-art performance considering several performance metrics, 〈 Acc , Sens , Spec , F1-score , MCC , AUC 〉 ≡ 〈 98.60%, 99.05%, 97.33%, 99.05%, 96.42%, 98.19% 〉, where Acc , Sens , Spec , F1-score , MCC , and AUC represents the accuracy, sensitivity, specificity, F1-score, Matthews correlation coefficient, and area-under-the-curve, respectively. We believe our proposed approach will play a crucial role in the planning of clinical treatment and guidelines before surgery.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi223-vi223
Author(s):  
Andrés Cervio ◽  
Sebastían Giovannini ◽  
Sonia Hasdeu ◽  
Lucía Pertierra ◽  
Blanca Diez

Abstract BACKGROUND Maximal safe resection of brain tumors affecting language areas has been a matter of increasing interest worldwide in the last decades. Functional MRI, tractography, and awake cranial surgery are standard procedures in our department since 2006. The aim of this study was to describe our experience in a series of 58 patients who underwent awake cranial surgery with intraoperative language mapping. METHODS Retrospective study of 58 adult patients who underwent awake surgery for brain tumors between January 2006 and January 2021. Preoperative neuropsychological assessment served as inclusion criteria. Language was evaluated according to the BDAE (Boston diagnostic aphasia examination) and WAB (Western aphasia battery) and strength according to the MRC (Medical Research Council) motor scale in the preoperative, immediate postoperative, and 3-months follow up. Functional MRI and tractography depicting white-matter tracts, neuronavigation, cortical and subcortical stimulation were performed in all cases. Conscious sedation was the anesthetic technique (propofol, fentanyl, and NSAIDs). Minimum follow-up was 6 months. FINDINGS The average age was 35 years (16–74). The anatomopathological findings were: low-grade glioma in 75,8% (n = 44), high-grade glioma in 15,6% (n = 9) and others in 8,6% (n = 5). No complications were registered during postoperative course. At the immediate postoperative evaluation 65% of patients presented with speech disturbances but at the 3-months follow up speech recovery was observed in all cases. Only 1 patient remained with moderate aphasia. mRS score at 3- months follow up was ≤ 1 in 96% of patients. Two patients had a persistent moderate hemiparesis. CONCLUSION Tumor resection in awake patients showed to be a safe procedure, and well tolerated by the patients. Preoperative planning of anatomical and functional aspects and intraoperative neurophysiological assessment are the cornerstones for pursuing maximal safe resection.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mikael T. Erkkilä ◽  
David Reichert ◽  
Johanna Gesperger ◽  
Barbara Kiesel ◽  
Thomas Roetzer ◽  
...  

AbstractMaximal safe tumor resection remains the key prognostic factor for improved prognosis in brain tumor patients. Despite 5-aminolevulinic acid-based fluorescence guidance the neurosurgeon is, however, not able to visualize most low-grade gliomas (LGG) and infiltration zone of high-grade gliomas (HGG). To overcome the need for a more sensitive visualization, we investigated the potential of macroscopic, wide-field fluorescence lifetime imaging of nicotinamide adenine dinucleotide (NADH) and protoporphyrin IX (PPIX) in selected human brain tumors. For future intraoperative use, the imaging system offered a square field of view of 11 mm at 250 mm free working distance. We performed imaging of tumor tissue ex vivo, including LGG and HGG as well as brain metastases obtained from 21 patients undergoing fluorescence-guided surgery. Half of all samples showed visible fluorescence during surgery, which was associated with significant increase in PPIX fluorescence lifetime. While the PPIX lifetime was significantly different between specific tumor tissue types, the NADH lifetimes did not differ significantly among them. However, mainly necrotic areas exhibited significantly lower NADH lifetimes compared to compact tumor in HGG. Our pilot study indicates that combined fluorescence lifetime imaging of NADH/PPIX represents a sensitive tool to visualize brain tumor tissue not detectable with conventional 5-ALA fluorescence.


Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1546 ◽  
Author(s):  
Alena Kopkova ◽  
Jiri Sana ◽  
Tana Machackova ◽  
Marek Vecera ◽  
Lenka Radova ◽  
...  

Central nervous system (CNS) malignancies include primary tumors that originate within the CNS as well as secondary tumors that develop as a result of metastatic spread. Circulating microRNAs (miRNAs) were found in almost all human body fluids including cerebrospinal fluid (CSF), and they seem to be highly stable and resistant to even extreme conditions. The overall aim of our study was to identify specific CSF miRNA patterns that could differentiate among brain tumors. These new biomarkers could potentially aid borderline or uncertain imaging results onto diagnosis of CNS malignancies, avoiding most invasive procedures such as stereotactic biopsy or biopsy. In total, 175 brain tumor patients (glioblastomas, low-grade gliomas, meningiomas and brain metastases), and 40 non-tumor patients with hydrocephalus as controls were included in this prospective monocentric study. Firstly, we performed high-throughput miRNA profiling (Illumina small RNA sequencing) on a discovery cohort of 70 patients and 19 controls and identified specific miRNA signatures of all brain tumor types tested. Secondly, validation of 9 candidate miRNAs was carried out on an independent cohort of 105 brain tumor patients and 21 controls using qRT-PCR. Based on the successful results of validation and various combination patterns of only 5 miRNA levels (miR-30e, miR-140, let-7b, mR-10a and miR-21-3p) we proposed CSF-diagnostic scores for each tumor type which enabled to distinguish them from healthy donors and other tumor types tested. In addition to this primary diagnostic tool, we described the prognostic potential of the combination of miR-10b and miR-196b levels in CSF of glioblastoma patients. In conclusion, we performed the largest study so far focused on CSF miRNA profiling in patients with brain tumors, and we believe that this new class of biomarkers have a strong potential as a diagnostic and prognostic tool in these patients.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi98-vi98
Author(s):  
Radim Jancalek ◽  
Martin Smrcka ◽  
Alena Kopkova ◽  
Jiri Sana ◽  
Marek Vecera ◽  
...  

Abstract Cerebrospinal fluid (CSF) baths extracellular environment of the central nervous system, and thus, it is ideal source of tumor diagnostic biomarkers like microRNAs (miRNAs), short non-coding RNAs involved in the pathogenesis of many cancers. As dysregulated levels of brain tumor specific miRNAs have been already observed in CSF, analysis of CSF miRNAs in brain tumor patients might help to develop new diagnostic platform. Next-Generation sequencing (NGS) was performed for analysis of small RNAs in 89 CSF samples taken from 32 glioblastomas (GBM), 14 low-grade gliomas (LGG), 11 meningiomas, 13 brain metastases and 19 non-tumor donors. Subsequently, according to NGS results levels of 10 miRNAs were measured in independent set of CSF samples (41 GBM, 44 meningiomas, 12 brain metastases and 20 non-tumor donors) using TaqMan Advanced miRNA Assays. NGS analysis revealed 22, 12 and 35 CSF miRNAs with significantly different levels in GBM, meningiomas, and brain metastases (adj.p < 0.0005, adj.p < 0.01, and adj.p < 0.005) respectively, in comparison with non-tumor CSF samples. Subsequent validation of selected CSF miRNAs has confirmed different levels of 7 miRNAs in GBM, 2 in meningiomas, and 2 in brain metastases compared to non-tumors. Panel of miR-30e-5p and miR-140-5p was able to distinguish brain metastases with 65% sensitivity and 100% specificity compared to non-tumor samples (AUC = 0.8167); panel of miR-21-3p and miR-196-5p classified metastatic patients with 78% sensitivity and 92 % specificity in comparison to GBM (AUC = 0.90854) and with 75% sensitivity and 83% specificity compared to meningiomas (AUC = 0.84848). We have observed that CSFs from patients with various primary brain tumors and metastases are characterized by specific miRNA signatures. This work was supported by the Ministry of Health, Czech Republic grant nr. NV18-03-00398 and the Ministry of Education, Youth and Sports, Czech Republic under the project CEITEC 2020 (LQ1601).


2016 ◽  
Vol 126 (6) ◽  
pp. 1772-1778 ◽  
Author(s):  
Michael C. Dewan ◽  
Reid C. Thompson ◽  
Steven N. Kalkanis ◽  
Fred G. Barker ◽  
Constantinos G. Hadjipanayis

OBJECTIVEAntiepileptic drugs (AEDs) are often administered prophylactically following brain tumor resection. With conflicting evidence and unestablished guidelines, however, the nature of this practice among tumor surgeons is unknown.METHODSOn November 24, 2015, a REDCap (Research Electronic Database Capture) survey was sent to members of the AANS/CNS Section on Tumors to query practice patterns.RESULTSResponses were received from 144 individuals, including 18.8% of board-certified neurosurgeons surveyed (across 86 institutions, 16 countries, and 5 continents). The majority reported practicing in an academic setting (85%) as a tumor specialist (71%). Sixty-three percent reported always or almost always prescribing AED prophylaxis postoperatively in patients with a supratentorial brain tumor without a prior seizure history. Meanwhile, 9% prescribed occasionally and 28% rarely prescribed AED prophylaxis. The most common agent was levetiracetam (85%). The duration of seizure prophylaxis varied widely: 25% of surgeons administered prophylaxis for 7 days, 16% for 2 weeks, 21% for 2 to 6 weeks, and 13% for longer than 6 weeks. Most surgeons (61%) believed that tumor pathology influences epileptogenicity, with high-grade glioma (39%), low-grade glioma (31%), and metastases (24%) carrying the greatest seizure risk. While the majority used prophylaxis, 62% did not believe or were unsure if prophylactic AEDs reduced seizures postoperatively. The vast majority (82%) stated that a well-designed randomized trial would help guide their future clinical decision making.CONCLUSIONSWide knowledge and practice gaps exist regarding the frequency, duration, and setting of AED prophylaxis for seizure-naive patients undergoing brain tumor resection. Acceptance of universal practice guidelines on this topic is unlikely until higher-level evidence supporting or refuting the value of modern seizure prophylaxis is demonstrated.


2020 ◽  
Vol 6 (2) ◽  
pp. 67-72
Author(s):  
Masih Rezaee ◽  
◽  
Bahram Amin Mansour ◽  

Background and Aim: The survival rate of brain tumors has not yet been reported in Iran. The purpose of this study, given the lack of such information, was to evaluate the 3-year survival rate in patients with all kinds of glioma tumors. Methods and Materials/Patients: This study was descriptive and retrospective, including 222 patients who had been diagnosed clinically with one type of glioma tumor and admitted to Al-Zahra hospital, Isfahan, Iran during 2001-2010. All patients (for minors, their parents) were contacted by phone. They were asked about the 3-year survival rate following their tumor resection surgery. Data such as patient’s age on admission, gender, histological diagnosis of tumor, and treatment regimen (surgical/non-surgical, radiation, and/or chemotherapy) were collected from medical records. The 3-year survival rate and frequency of each tumor based on age and gender were measured. Results: The 3-year survival rates for Glioblastoma Multiform (GBM) and anaplastic astrocytoma were 8.7% and 0%, respectively following surgery and chemo-radiation. These tumors were categorized as high-grade glioma with poor prognosis. The 3-year survival rate for diffuse astrocytoma, low-grade oligodendroglioma, low-grade ependymoma, and pilocytic astrocytoma following surgery and radiation were 100%, 95.2%, 100%, and 100%, respectively. These tumors were categorized as low-grade glioma, which has a good prognosis. Conclusion: In this study, the 3-year survival rate in patients with low-grade glioma following surgery and radiation was almost 100%. In contrast, the 3-year survival rate in patients with highgrade glioma following surgery and chemo-radiation was almost 0%.


1978 ◽  
Vol 49 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Takao Hoshino ◽  
Kazuhiro Nomura ◽  
Charles B. Wilson ◽  
Kathy D. Knebel ◽  
Joe W. Gray

✓ Flow cytometry (FCM) is a technique that measures the quantity of DNA contained in individual nuclei and records a frequency distribution of the DNA content per nucleus in the sampled cell population. Nuclei from a variety of human brain-tumor types were isolated by means of tissue grinding, purified by centrifugation through 40% sucrose (15 minutes at 4000 rpm), fixed with 10% formalin, stained with acriflavin-Feulgen, and analyzed by FCM. Profiles of DNA distribution in histologically benign tumors, such as meningiomas, pituitary adenomas, neuroblastomas, and low-grade astrocytomas, revealed a large diploid population (2C) with a few nuclei in DNA synthesis, as well as a small premitotic population (G2 cells) that contains a 4C DNA complement. In contrast, malignant gliomas, including glioblastomas, consist of more cells in DNA synthesis; these tumor cells show a highly variable distribution of ploidy consisting not only of diploid, and/or aneuploid, but also of triploid, tetraploid, and possibly octaploid populations. Also, a large variability between different regions of each tumor was always observed. In contrast, metastatic brain tumors, despite the fact that they contain a considerable number of cells undergoing DNA synthesis, demonstrate little variability within each individual tumor. The ability to rapidly characterize the cell populations of human brain tumors with FCM may enhance the effectiveness of their clinical management.


2018 ◽  
Vol 8 (11) ◽  
pp. 202 ◽  
Author(s):  
Maria Pino ◽  
Alessia Imperato ◽  
Irene Musca ◽  
Rosario Maugeri ◽  
Giuseppe Giammalva ◽  
...  

Maximal safe resection represents the gold standard for surgery of malignant brain tumors. As regards gross-total resection, accurate localization and precise delineation of the tumor margins are required. Intraoperative diagnostic imaging (Intra-Operative Magnetic Resonance-IOMR, Intra-Operative Computed Tomography-IOCT, Intra-Operative Ultrasound-IOUS) and dyes (fluorescence) have become relevant in brain tumor surgery, allowing for a more radical and safer tumor resection. IOUS guidance for brain tumor surgery is accurate in distinguishing tumor from normal parenchyma, and it allows a real-time intraoperative visualization. We aim to evaluate the role of IOUS in gliomas surgery and to outline specific strategies to maximize its efficacy. We performed a literature research through the Pubmed database by selecting each article which was focused on the use of IOUS in brain tumor surgery, and in particular in glioma surgery, published in the last 15 years (from 2003 to 2018). We selected 39 papers concerning the use of IOUS in brain tumor surgery, including gliomas. IOUS exerts a notable attraction due to its low cost, minimal interruption of the operational flow, and lack of radiation exposure. Our literature review shows that increasing the use of ultrasound in brain tumors allows more radical resections, thus giving rise to increases in survival.


2015 ◽  
Vol 38 (1) ◽  
pp. E7 ◽  
Author(s):  
Masayuki Nitta ◽  
Yoshihiro Muragaki ◽  
Takashi Maruyama ◽  
Soko Ikuta ◽  
Takashi Komori ◽  
...  

OBJECT There is no standard therapeutic strategy for low-grade glioma (LGG). The authors hypothesized that adjuvant therapy might not be necessary for LGG cases in which total radiological resection was achieved. Accordingly, they established a treatment strategy based on the extent of resection (EOR) and the MIB-1 index: patients with a high EOR and low MIB-1 index were observed without postoperative treatment, whereas those with a low EOR and/or high MIB-1 index received radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the authors reviewed clinical data on patients with primarily diagnosed LGGs who had been treated according to the above-mentioned strategy, and they validated the treatment policy. Given their results, they will establish a new treatment strategy for LGGs stratified by EOR, histological subtype, and molecular status. METHODS One hundred fifty-three patients with diagnosed LGG who had undergone resection or biopsy at Tokyo Women's Medical University between January 2000 and August 2010 were analyzed. The patients consisted of 84 men and 69 women, all with ages ≥ 15 years. A total of 146 patients underwent surgical removal of the tumor, and 7 patients underwent biopsy. RESULTS Postoperative RT and nitrosourea-based chemotherapy were administered in 48 and 35 patients, respectively. Extent of resection was significantly associated with both overall survival (OS; p = 0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy significantly prolonged PFS, especially in patients with oligodendroglial subtypes (p = 0.0009). Patients with a mutant IDH1 gene had significantly longer OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as prognostic factors, but it did identify chemotherapy as a prognostic factor for PFS and EOR as a prognostic factor for OS and PFS. CONCLUSIONS The findings demonstrated that EOR was significantly correlated with patient survival; thus, one should aim for maximum tumor resection. In addition, patients with a higher EOR can be safely observed without adjuvant therapy. For patients with partial resection, postoperative chemotherapy should be administered for those with oligodendroglial subtypes, and repeat resection should be considered for those with astrocytic tumors. More aggressive treatment with RT and chemotherapy may be required for patients with a poor prognosis, such as those with diffuse astrocytoma, 1p/19q nondeleted tumors, or IDH1 wild-type oligodendroglial tumors with partial resection.


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