p15和WIF－1在人脑胶质瘤中的表达及其临床意义

目的：探讨p15和WIF－1在人脑神经胶质瘤中的表达,及其与临床病理特征和生物学行为的关系。方法：应用免疫组化SP法检测53例神经胶质瘤和20例正常脑组织中p15和WIF－1蛋白的表达,结合病例随访资料分析其临床意义。结果：p15及WIF－1蛋白在神经胶质瘤中的阳性表达率明显低于正常脑组织,差异具有统计学意义（P＜0．05）;p15及WIF－1蛋白的阳性表达率与神经胶质瘤的病理学分级和瘤周脑水肿具有相关性（P＜0．05）,但与性别和年龄不相关（P＞0．05）。p15和WIF－1蛋白在神经胶质瘤中的阳性表达率复发组与无复发组有明显差异（P＜0．05）。p15与WIF－1蛋白的表达呈正相关（r＝－0．396,P＜0．01）。结论：p15、WIF－1的表达与人神经胶质瘤的发生及进展相关;p15、WIF －1低表达患者预后较差。联合检测p15、WIF－1蛋白的表达对神经胶质瘤的早期诊断、判断预后有参考价值。     

Knockdown of microRNA-127 reverses adriamycin resistance via cell cycle arrest and apoptosis sensitization in adriamycin-resistant human glioma cells

The aim of this study was to investigate signaling pathways for reversal of microRNA-127-mediated multi-drug resistance (MDR) in gliomas cells. Adriamycin-resistant glioma cell lines U251/adr and U87-MG/adr were established and we found that anti-microRNA-127 markedly reduced microRNA-127 expression levels in a time-dependent manner, leading to distinct inhibition of cell proliferation and increased apoptosis and the content of intracellular Rh123. Silencing of microRNA-127 significantly increased the sensitivity of U251/ADR and U87-MG/adr cells to adriamycin, compared to cells transfected with negative control siRNA. Silencing of microRNA-127 also significantly reduced the mRNA and protein expression levels of MDR1 and MRP1, which are major ATP-binding cassette (ABC) transporter linked to multi-drug resistance in cancer cells. And Runx2, p53, bcl-2 and survivin, which are important role in cell apoptosis, also markedly changed after microRNA-127 silencing. In addition, down-regulating microRNA-127 decreased the level of phosphorylated-Akt. Our data indicate that down-regulation of micorRNA-127 can trigger apoptosis and overcome drug resistance of gliomas cells. Therefore, this resistance of adriamycin in gliomas can be cancelled by silencing expression of microRNA-127.     

3D-CRT versus RapidArc in Deep Tempero-Parietal High Grade Gliomas: Do We Really Need Higher Technology?

Purpose: The aim of this study was to dosimetrically compare single arc RapidArc with conventional 3D-CRT plans for tempero-parietal high grade gliomas with respect to PTV coverage and doses perceived by surrounding critical organs at risk. Methods: Thirty patients with the pathological diagnosis of high grade gliomas (WHO grade III-IV) were selected to be enrolled in our study. Patients were referred to our center (center of Clinical Oncology and Radiotherapy, Cairo University) during the period March 2020 till June 2021 for post-operative irradiation using 3D-CRT technique. For all patients, the dose prescribed to the planning target volume (PTV) was 60 Gy in 30 fractions. A RA plan was performed for each patient and dosimetrically was compared to the 3D-CRT plan. Results: The PTV coverage in terms of V95% was significantly superior in the RA plans with values of 98.4 ± 1.7 compared to 94.4 ± 2.6 for the 3D-CRT plans (p-value of 0.004). The doses risk structures ( eyes, optic nerves and cochleae)  was lower with the RA plans as contrasted to the 3D-CRT plan with an exception for the  intraocular lens which received higher doses in the RA plan with a statistically significant p-value of 0.001 and 0.002 for the  Ipsilateral and contralateral lens, respectively. The average number of MUs ± SD was 358.6± 44.4 for the RA plans versus 247.6 ± 16.1 for 3D-CRT plans (p-value 0.001). The Dmean of healthy brain tissue was nearly equal for both plans (p-value of 0.071). Conclusion: The plans achieved by RA showed superior dose conformity, PTV coverage, more homogeneous dose distribution when contrasted to 3D-CRT plans. With the exception of both intraocular lenses, the RA plans showed better OAR sparing and utilized a higher number of MUs compared to the 3D-CRT.     

Dosimetric Comparison and Feasibility of Simultaneous Integrated Boost (SIB) in Treatment of Malignant Gliomas Using Intensity Modulated Radiotherapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT)

Objective: To evaluate the dosimetric parameters of Simultaneous Integrated Boost in the treatment of malignantgliomas and compare the SIB plans of VMAT and IMRT. Methodology: CT and MRI of 28 patients were used forgenerating SIB plans with VMAT and IMRT. A dose of 2Gy per fraction was prescribed to the CPTV and 2.4Gy tothe GPTV for a total of 25 fractions. The plans were accepted only if they met the set of planning objectives definedin the protocol. Results: We could achieve the planning objectives in all the SIB plans. Although GPTV coverage wasstatistically better in VMAT (98.67% vs 98.19% ;p=0.024) the difference is not clinically meaningful. The conformityindex for GPTV was higher in IMRT (0.83 vs 0.76; p=0.001). The coverage of CPTV was better in IMRT(97.88% vs 96.87%; p=0.021). But the conformity index of CPTVannulus was higher in VMAT (0.72 vs 0.67; p=0.01).There was no difference in homogeneity index of GPTV and CPTV annulus between the plans. The mean dose receivedby normal brain was higher in IMRT (28Gy vs 24.2Gy; p<0.001). Ipsilateral optic nerve has received lesser Dmax inIMRT (44.2Gy vs 46.95Gy; p=0.02). No difference was seen in Dmax of brainstem, optic chiasm, contralateral opticnerve. The treatment times and monitor units were significantly less in VMAT. Conclusion: SIB is dosimetricallyfeasible for hypofractionation in malignant gliomas using IMRT and VMAT. IMRT plans had better boost conformity,lower ipsilateral optic nerve and brainstem maximum doses compared to VMAT. Whereas, VMAT had better coverage,better overall PTV conformity, lower normal brain mean dose, lower monitor units and lesser treatment times. Althoughplanning of VMAT is cumbersome and time consuming, the advantage of reducing treatment time is beneficial tothe patients’ comfort and better managing of patient load in high volume centres.     

人脑胶质瘤中cyclin E的表达及其与细胞凋亡的关系

目的 研究人脑胶质瘤中cyclin E蛋白的表达与肿瘤恶性程度的关系及其对细胞凋亡的影响.方法 采用免疫组化法和原位细胞凋亡检测TUNEL法分别检测47例脑胶质瘤中cyclin E的表达和凋亡细胞,计算两者阳性目标PU值,统计分析两者之间及其与胶质瘤病理分级之间的关系.结果 正常脑组织中无cyclin E表达.随着人脑胶质瘤病理分级的增高,cyclin E平均PU值明显升高.在WHO分级Ⅰ～Ⅳ级胶质瘤中,存在显著性差异(F=61.67,P＜0.01),其中高度恶性组cyclin E(PU)明显高于低度恶性组cyclin E(PU)(t=8.08,P＜0.01),差异有显著性意义.类似cyclin E,凋亡指标(AI)PU值随脑胶质瘤恶性程度增高而升高(F=12.20,P＜0.01).cyclin E(PU)与AI(PU)呈明显正相关(r=0.703,P＜0.01).结论 人脑胶质瘤中cyclin E的表达与细胞凋亡和病理学分级密切相关,很可能参与了人脑胶质瘤的发生和恶性转化.     

miR‐3184‐3p enriched in cerebrospinal fluid exosomes contributes to progression of glioma and promotes M2‐like macrophage polarization

Liquid biopsy is a novel strategy for tumour diagnosis. The contents of cerebrospinal fluid (CSF) exosomes could reflect glioma status, hence sampling exosomes from CSF is a means of liquid biopsy for glioma. However, few studies have focused on the function of microRNAs in CSF exosomes. In this study, we found that miR‐3184‐3p was enriched in CSF exosomes in glioma patients and was downregulated after tumour resection. We found that miR‐3184 facilitates glioma progression in two ways. On the one hand, miR‐3184 directly promotes proliferation, migration, and invasion while inhibiting apoptosis in glioma. On the other hand, miR‐3184 in glioma‐derived exosomes polarizes macrophages to an M2‐like phenotype, which further aggravates tumour progression. Overall, the current findings uncovered a new mechanism and highlighted the significant role of miR‐3184 in glioma progression. Furthermore, exosomal miR‐3184 could be a considerable factor with potential applications in glioma diagnosis and treatment in the future.     

CT引导125I放射性粒子植入治疗复发性脑胶质瘤的研究

目的：探讨^125I放射粒子植入治疗复发性脑胶质瘤的技术方法、疗效和安全性。方法：33例手术或放疗后复发性脑胶质瘤患者行CT引导下^125I粒子植入术,根据术前计划确定粒子数目、空间分布和粒子针数目。粒子活度为0．4-0．8mCi,间距为0．5～1.0cm,共植入粒子10～35颗,术后即刻行CT扫描并进行质量验证。术后定期复查CT。结果：按照WHO疗效评价标准,1、3和6个月时有效率分别为48．5％、67．7％和80．0％。全组中位生存期16个月,其中1～2级胶质瘤中位生存期26个月,3～4级胶质瘤中位生存期11个月;全组1年生存率为66．7％（22／33）,其中1～2级胶质瘤1年生存率为85．0％（17／20）,3～4级胶质瘤1年生存率为38．5％（5／13）。并发症包括针道少量出血4例,局部脑坏死5例。未出现与治疗相关的死亡病例。结论：CT引导^125I粒子植入治疗复发性脑胶质瘤具有安全、微创、并发症少和疗效肯定等优点,值得进一步应用。     

Characterization and clinical implications of different malignant transformation patterns in diffuse low-grade gliomas

Malignant transformation (MT) of low-grade gliomas (LGGs) to a higher-grade variant seems inevitable, yet it remains unclear which LGG patients will progress to grade 3 or even directly to grade 4 after receiving a long course of treatment. To elucidate this, we conducted a retrospective cohort study based on 229 adults with recurrent LGG. Our study aimed to disclose the characteristics of different MT patterns and to build predictive models for patients with LGG. Patients were allocated into group 2–2 (n = 81, 35.4%), group 2–3 (n = 91, 39.7%), and group 2–4 (n = 57, 24.9%), based on their MT patterns. Patients who underwent MT showed lower Karnofsky performance scale (KPS) scores, larger tumor sizes, smaller extents of resection (EOR), higher Ki-67 indices, lower rates of 1p/19q codeletion, but higher rates of subventricular involvement, radiotherapy, chemotherapy, astrocytoma, and post-progression enhancement (PPE) compared with those in group 2–2 (p < 0.01). On multivariate logistic regression, 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score were independently associated with MT (p < 0.05). Survival analyses demonstrated that patients in group 2–2 had the longest survival, followed by group 2–3 and then group 2–4 (p < 0.0001). Based on these independent parameters, we constructed a nomogram model that exhibited superior potential (sensitivity: 0.864, specificity: 0.814, and accuracy: 0.843) compared with PPE in early prediction of MT. Combining the factors of 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score that were presented at initial diagnosis could precisely forecast the subsequent MT patterns of patients with LGG.