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《Expert review of anticancer therapy》2013,13(11):1739-1748
Recent years have witnessed an explosion of promising therapies for cancer patients. New insights into the biology of malignancies have led to the development of targeted agents with the potential to improve survival and quality of life. One of the most important classes of these compounds are tyrosine kinase inhibitors. These agents are beginning to offer a clinically relevant benefit to patients with tumors that until recently have been refractory to medical therapies. High-grade gliomas represent one class of medically refractory solid tumors. This article summarizes the state of the art of tyrosine kinase inhibitors in the management of patients with high-grade gliomas. 相似文献
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Thomas Perwein Martin Benesch Daniela Kandels Torsten Pietsch Ren Schmidt Franz Quehenberger Brigitte Bison Monika Warmuth-Metz Beate Timmermann Jürgen Krauss Ulrich-Wilhelm Thomale Rolf-Dieter Kortmann Pablo Herniz Driever Astrid Katharina Gnekow 《Neuro-oncology》2021,23(7):1148
BackgroundKnowledge on management of pediatric spinal cord low-grade glioma (LGG) is scarce.MethodsWe analyzed clinical datasets of 128 pediatric patients with spinal LGG followed within the prospective multicenter trials HIT-LGG 1996 (n = 36), SIOP-LGG 2004 (n = 56), and the subsequent LGG-Interim registry (n = 36).ResultsSpinal LGG, predominantly pilocytic astrocytomas (76%), harbored KIAA1549-BRAF fusion in 14/35 patients (40%) and FGFR1-TACC1 fusion in 3/26 patients (12%), as well as BRAFV600E mutation in 2/66 patients (3%). 10-year overall survival (OS) and event-free survival (EFS) was 93% ± 2% and 38% ± 5%, respectively. Disseminated disease (n = 16) was associated with inferior OS and EFS, while age ≥11 years and total resection were favorable factors for EFS. We observed 117 patients following total (n = 24) or subtotal/partial resection (n = 74), biopsy (n = 16), or radiologic diagnosis only (n = 3). Eleven patients were treated first with chemotherapy (n = 9) or irradiation (n = 2). Up to 20.8 years after diagnosis/initial intervention, 73/128 patients experienced one (n = 43) or up to six (n = 30) radiological/clinical disease progressions. Tumor resections were repeated in 36 patients (range, 2-6) and 47 patients required nonsurgical treatment (chemotherapy, n = 20; radiotherapy, n = 10; multiple treatment lines, n = 17). Long-term disease control for a median of 6.5 (range, 0.02-20) years was achieved in 73/77 patients following one (n = 57) or repeated (n = 16) resections, and in 35/47 patients after nonsurgical treatment.ConclusionsThe majority of patients experienced disease progression, even after years. Multiple interventions were required for more than a third, yet multimodal treatment enabled long-term disease control. Molecular testing may reveal therapeutic targets. 相似文献
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目的探讨脑胶质瘤的MRI影像表现及其与脑胶质瘤组织中白细胞介素-17(IL-17)、白细胞介素-24(IL-24)、血管内皮生长因子(VEGF)、胶质纤维酸性蛋白(GFAP)阳性表达的相关性。方法回顾性分析我院神经外科68例经手术病理证实为脑胶质瘤患者的临床资料并将其纳入研究组,以79例因脑出血行开颅手术患者为对照组。分析研究组患者的MRI影像表现并通过HE染色、免疫组化SP法检测2组患者中IL-17、IL-24、VEGF、GFAP表达的差异性,应用Speraman等级相关分析IL-17、IL-24、VEGF、GFAP表达与MRI表现的关系。结果脑胶质瘤位于大脑半球者65例(95.59%),脑胶质瘤位于小脑半球者3例(4.41%)。66例(97.06%)表现为T1WI低、T2WI混杂信号伴周围中—重度水肿,2例(2.94%)表现为T1WI稍高、T2WI混杂信号;肿瘤内出血31例(45.58%),无出血37例(54.42%);2例(2.94%)表现为轻度水肿,2例(2.94%)表现为中度水肿,64例(94.12%)表现为重度水肿;44例(64.71%)脑胶质瘤内见流空血管影,脑胶质瘤生长速度快,瘤体均较大,最大截面为0.7 cm×1.2 cm~10.3 cm×9.6 cm,形态不规则。DWI呈弥散受限改变66例(97.06%),无弥散受限2例(2.94%);增强扫描后均匀强化59例(86.76%),不均匀9例(13.24%);59例(86.76%)呈花环状或花瓣状明显强化,环壁部分呈栅栏状,9例(13.24%)呈轻度结节状强化。IL-17、VEGF在对照组中不表达,研究组IL-17、VEGF表达阳性率高于对照组,IL-24、GFAP表达阳性率低于对照组,差异均有统计学意义(P<0.05)。Speraman等级相关分析显示,IL-24、GFAP表达阳性率随脑胶质瘤分级升高呈下降趋势,呈显著负相关(r=-0.711、-0.577,P<0.05);IL-17、VEGF表达阳性率随脑胶质瘤分级升高呈上升趋势,以Ⅳ型胶质瘤表达最高,呈显著正相关(r=0.670、0.614,P<0.05)。结论脑胶质瘤MRI表现具有瘤体大、累及脑叶多、形态不规则,信号不均匀,水肿明显的特点,肿瘤组织中IL-17、IL-24、VEGF、GFAP的阳性表达能够反映脑胶质瘤分级程度。 相似文献
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Macoura Gadji Ana‐Maria Crous‐Tsanaclis David Mathieu Sabine Mai David Fortin Régen Drouin 《Neuropathology》2014,34(2):170-178
The combined 1p‐/19q‐ deletions in oligodendrogliomas originate from translocation between both chromosomes. In the few cases of oligoastrocytomas and glioblastomas with an oligodendroglioma component (GBMO) where only 1p deletion was described, the origin remains unknown. We report the first case of GBMO, in which a single 1p deletion was detected and was linked to a translocation between chromosomes 1 and 7. Fresh surgical specimens were collected during surgery and the samples were used for cell culture, touch preparation smear slides (TP slides) and DNA extraction. Peripheral venous blood was also collected from the patient. G‐banding using Trypsin and stained with Giemsa (GTG) banding and karyotyping were performed and 1p‐/19q‐, TP53, PTEN and c‐MYC were analyzed by fluorescent in situ hybridization (FISH). Multicolor FISH (mFISH) and microsatellites analyses were also performed to complete the investigation. Three‐dimensional quantitative FISH (3D‐QFISH) of telomeres was performed on nuclei from TP slides and analyzed using TeloViewTM to determine whether the 3D telomere profile as an assessment of telomere dysfunction and a characterization of genomic instability could predict the disease aggressiveness. An unbalanced chromosomal translocation was found in all metaphases and confirmed by mFISH. The karyotype of the case is: 50~99,XXX, +der(1;7)(q10;p10),inc[47] The derivative chromosome was found in all 47 analyzed cells, but the number of derivatives varied from one to four. There was neither imbalance in copy number for genes TP53 and PTEN, nor amplification of c‐MYC gene. We did not find loss of heterozygosity with analysis of microsatellite markers for chromosomes 1p and 19q in tumor cells. The 3D‐telomere profile predicted a very poor prognostic and short‐term survival of the patient and highlights the potential clinical power of telomere signatures as a solid biomarker of GBMO. Furthermore, this translocation between chromosomes 1 and 7 led to a singular 1p deletion in this GBMO and may generate the 1p and 7q deletions. 相似文献
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Marie Blanchette Luc Tremblay Martin Lepage David Fortin 《Journal of cerebral blood flow and metabolism》2014,34(5):820-826
Drug delivery to the brain is influenced by the blood–brain barrier (BBB) and blood–tumor barrier (BTB) to an extent that is still debated in neuro-oncology. In this paper, we studied the delivery across the BTB and the BBB of compounds with different molecular sizes in normal and glioma-bearing rats. Studies were performed at baseline as well as after an osmotic BBB disruption (BBBD) using dynamic contrast-enhanced magnetic resonance imaging and two T1 contrast agents (CAs), Magnevist (743 Da) and Gadomer (17,000 Da). More specifically, we determined the time window for the BBB permeability, the distribution and we calculated the brain exposure to the CAs. A different pattern of accumulation and distribution at baseline as well as after a BBBD procedure was observed for both agents, which is consistent with their different molecular size and weight. Baseline tumor exposure was threefold higher for Magnevist compared with Gadomer, whereas postBBBD tumor exposure was twofold higher for Magnevist. Our study clearly showed that the time window and the extent of delivery across the intact, as well as permeabilized BTB and BBB are influenced by drug size. 相似文献
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Charlotte Dufour Romain Perbet Pierre Leblond Romain Vasseur Laurence Stechly Adeline Pierache Nicolas Reyns Gustavo Touzet Emilie Le Rhun Matthieu Vinchon Claude‐Alain Maurage Fabienne Escande Florence Renaud 《Brain pathology (Zurich, Switzerland)》2020,30(1):179-190
Pediatric diffuse midline gliomas are devastating diseases. Among them, diffuse midline gliomas H3K27M‐mutant are associated with worse prognosis. However, recent studies have highlighted significant differences in clinical behavior and biological alterations within this specific subgroup. In this context, simple markers are needed to refine the prognosis of diffuse midline gliomas H3K27M‐mutant and guide the clinical management of patients. The aims of this study were (i) to describe the molecular, immunohistochemical and, especially, chromosomal features of a cohort of diffuse midline gliomas and (ii) to focus on H3K27M‐mutant tumors to identify new prognostic markers. Patients were retrospectively selected from 2001 to 2017. Tumor samples were analyzed by immunohistochemistry (including H3K27me3, EGFR, c‐MET and p53), next‐generation sequencing and comparative genomic hybridization array. Forty‐nine patients were included in the study. The median age at diagnosis was 9 years, and the median overall survival (OS) was 9.4 months. H3F3A or HIST1H3B mutations were identified in 80% of the samples. Within the H3K27M‐mutant tumors, PDGFRA amplification, loss of 17p and a complex chromosomal profile were significantly associated with worse survival. Three prognostic markers were identified in diffuse midline gliomas H3K27M‐mutant: PDGFRA amplification, loss of 17p and a complex chromosomal profile. These markers are easy to detect in daily practice and should be considered to refine the prognosis of this entity. 相似文献