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1.
目的:通过检测肿瘤组织中O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)的表达,探讨其与胃肠胰神经内分泌瘤以替莫唑胺为基础化疗患者预后的相关性。方法:收集2017年至2019年在我院接受替莫唑胺联合替吉奥化疗的15例晚期胃肠胰神经内分泌瘤患者的肿瘤组织,采用免疫组织化学法检测肿瘤组织中MGMT蛋白表达情况,根据表达情况分为MGMT阴性组和MGMT阳性组,并对患者长期随访,进行无进展生存时间和药物安全性的评定,对MGMT表达水平与替莫唑胺治疗效果行相关性分析。结果:15例患者肿瘤组织MGMT表达阴性者为8例(53.3%),MGMT表达阳性者为7例(46.7%);MGMT阴性组患者化疗6个疗程后,客观缓解率(ORR)为35.7%(3/8),明显高于MGMT阳性组的0(0/7);MGMT表达阳性组患者的中位无进展生存时间(mPFS)为6个月,而MGMT表达阴性组患者的mPFS目前无法得出,但明显长于MGMT阳性组,两组间差异具有统计学意义(P=0.000 2)。化疗不良反应均为2级以下的骨髓抑制和消化道反应。结论:基于替莫唑胺化疗方案的疗效与MGMT在肿瘤组织中的表达状态相关,MGMT表达与否可以用作胃肠胰神经内分泌瘤患者对替莫唑胺治疗反应的生物学指标。  相似文献   
2.
目的探讨鸦胆子油乳联合阿帕替尼及替莫唑胺治疗复发性恶性脑胶质瘤患者的临床疗效、免疫功能影响及不良反应。方法选取2016年6月至2018年12月期间郑州大学第一附属医院复发性恶性脑胶质瘤患者52例,随机分为2组,A组26例应用阿帕替尼及替莫唑胺治疗,B组26例应用鸦胆子油乳联合阿帕替尼及替莫唑胺治疗,比较2组临床疗效、免疫功能及不良反应。结果治疗后,B组客观缓解率为69.23%,高于A组的38.46%(P<0.05)。治疗后,A组CD3+T细胞、CD4+辅助性T细胞、CD4+/CD8+较治疗前显著降低(P均<0.05),而B组上述指标较治疗前显著升高(P均<0.05),且均显著高于A组(P<0.05)。治疗后,B组KPS评分高于治疗前,且高于A组(P均<0.05)。B组不良反应发生率低于A组,但差异无统计学意义(P>0.05),且不良反应轻微可耐受,对症处理后消失。B组6个月疾病无进展生存率65.4%、中位疾病无进展生存期7.56个月(95%CI:5.72~9.40个月)、中位总生存期10.14个月(95%CI:8.59~11.70个月),均明显高于A组的46.2%、5.78个月(95%CI:4.64~6.92个月)、8.73个月(95%CI:8.22~9.25个月)(P均<0.05)。结论鸦胆子油乳联合阿帕替尼及替莫唑胺治疗复发性恶性脑胶质瘤可提高近期临床治疗效果,调节患者免疫功能,改善其生活质量和生存,且安全性良好,值得临床应用推广。  相似文献   
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4.
Resistance of glioblastoma to the chemotherapeutic compound temozolomide is associated with the presence of glioblastoma stem cells in glioblastoma and is a key obstacle for the poor prognosis of glioblastoma. Here, we show that phospholipase D1 is elevated in CD44High glioblastoma stem cells and in glioblastoma, especially recurring glioblastoma. Phospholipase D1 elevation positively correlated with the level of CD44 and poor prognosis in glioblastoma patients. Temozolomide significantly upregulated the expression of phospholipase D1 in the low and moderate CD44 populations of glioblastoma stem cells, but not in the CD44High population in which phospholipase D1 is highly expressed. Phospholipase D1 conferred resistance to temozolomide in CD44High glioblastoma stem cells and increased their self-renewal capacity and maintenance. Phospholipase D1 expression significantly correlated with levels of temozolomide resistance factors, which were suppressed by microRNA-320a and -4496 induced by phospholipase D1 inhibition. Genetic and pharmacological targeting of phospholipase D1 attenuated glioblastoma stem cell-derived intracranial tumors of glioblastoma using the microRNAs, and improved survival. Treatment solely with temozolomide produced no benefits on the glioblastoma, whereas in combination, phospholipase D1 inhibition sensitized glioblastoma stem cells to temozolomide and reduced glioblastoma tumorigenesis. Together, these findings indicate that phospholipase D1 inhibition might overcome resistance to temozolomide and represents a potential treatment strategy for glioblastoma. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.  相似文献   
5.
Cancer remains the topmost disorder of the mankind and number of cases is unceasingly growing at unprecedented rates. Although the synthetic anti-cancer compounds still hold the largest market in the modern treatment of cancer, natural agents have always been tried and tested for potential anti-cancer properties. Thymoquinone (TQ), a monoterpene and main ingredient in the essential oil of Nigella sativa L. has got very eminent rankings in the traditional systems of medicine for its anti-cancer pharmacological properties. In this review we summarized the diverse aspects of TQ including its chemistry, biosynthesis, sources and pharmacological properties with a major concern being attributed to its anti-cancer efficacies. The role of TQ in different aspects involved in the pathogenesis of cancer like inflammation, angiogenesis, apoptosis, cell cycle regulation, proliferation, invasion and migration have been described. The mechanism of action of TQ in different cancer types has been briefly accounted. Other safety and toxicological aspects and some combination therapies involving TQ have also been touched. A detailed literature search was carried out using various online search engines like google scholar and pubmed regarding the available research and review accounts on thymoquinone upto may 2019. All the articles reporting significant addition to the activities of thymoquinone were selected. Additional information was acquired from ethno botanical literature focusing on thymoquinone. The compound has been the centre of attention for a long time period and researched regularly in quite considerable numbers for its various physicochemical, medicinal, biological and pharmacological perspectives. Thymoquinone is studied for various chemical and pharmacological activities and demonstrated promising anti-cancer potential. The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone. Further in-vitro and in-vivo research is strongly warranted regarding the complete exploration of thymoquinone in ethnopharmacological context.  相似文献   
6.
High-risk neuroblastoma, a predominantly TP53 wild-type (wt) tumour, is incurable in >50% patients supporting the use of MDM2 antagonists as novel therapeutics. Idasanutlin (RG7388) shows in vitro synergy with chemotherapies used to treat neuroblastoma. This is the first study to evaluate the in vivo efficacy of the intravenous idasanutlin prodrug, RO6839921 (RG7775), both alone and in combination with temozolomide in TP53 wt orthotopic neuroblastoma models. Detection of active idasanutlin using liquid chromatography-mass spectrometry and p53 pathway activation by ELISA assays and Western analysis showed peak plasma levels 1 h post-treatment with maximal p53 pathway activation 3–6 h post-treatment. RO6839921 and temozolomide, alone or in combination in mice implanted with TP53 wt SHSY5Y-Luc and NB1691-Luc cells showed that combined RO6839921 and temozolomide led to greater tumour growth inhibition and increase in survival compared to vehicle control. Overall, RO6839921 had a favourable pharmacokinetic profile consistent with intermittent dosing and was well tolerated alone and in combination. These preclinical studies support the further development of idasanutlin in combination with temozolomide in neuroblastoma in early phase clinical trials.  相似文献   
7.
Objective: Temozolomide (TMZ) improves Glioblastoma Multiforme (GBM) patient survival. The invasive behavior of the glioma cells is the cause of GBM relapse. The glioma BK ion channel (gBK) may provide glioma cells with a mechanism to invade surrounding tissue. gBK contains epitopes that cytolytic T lymphocytes (CTLs) can recognize and kill glioma cells. Fascin-1 is an actin crosslinking molecule that supports microvilli; these membrane protrusions provide a physical defense against CTLs. TMZ was investigated to determine its effect on gBK and fascin-1 expression.

Research design and methods: Human glioma cells cultured in TMZ were analyzed for their altered mRNA and gBK protein levels by using quantitative real time PCR, immunostaining and cellular functional assays.

Results: TMZ slowed glioma cell growth and inhibited their transmigratory properties due to loss of fascin-1. TMZ induced increased gBK and HLA expression and allowed these TMZ-treated cells to become better targets for gBK-specific CTLs.

Conclusions: Besides its traditional chemotherapeutic effect, TMZ can have four other targeted pathways: 1) slowed glioma cell growth; 2) inhibited glioma cell transmigration; 3) increased HLA-A2 and gBK tumor antigen production; 4) increased CTL-mediated cytolysis of the TMZ treated glioma cells due to the loss of their defensive membrane protrusions supported by fascin-1.  相似文献   
8.
BackgroundNo standard medical treatment exists for adult patients with recurrent ependymoma, and prospective clinical trials in this population have not succeeded because of its rarity and challenges in accruing patients. The Collaborative Ependymoma Research Network conducted a prospective phase II clinical trial of dose-dense temozolomide (TMZ) and lapatinib, targeting the unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter status and increased expression of ErbB2 (human epidermal growth factor receptor 2) and ErbB1 (epidermal growth factor receptor) in ependymomas.MethodsPatients age 18 or older with histologically proven and progressive ependymoma or anaplastic ependymoma were eligible and received dose-dense TMZ and daily lapatinib. The primary outcome measure was median progression-free survival (PFS). Landmark 6- and 12-month PFS and objective response were measured. Serial assessments of symptom burden using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT)/MDASI–Spine Tumor modules were collected.ResultsThe 50 patients enrolled had a median age of 43.5 years, median Karnofsky performance status of 90, and a median of 2 prior relapses. Twenty patients had grade III, 16 grade II, and 8 grade I ependymoma. Half had spinal cord tumors; 15 had a supratentorial tumor, 8 infratentorial, and 2 had disseminated disease. Treatment was well tolerated. The median PFS was 7.8 months (95% CI: 5.5,12.2); the 6- and 12-month PFS rates were 55% and 38%, with 2 complete and 6 partial responses. Measures of symptom burden showed reduction in moderate-severe pain and other disease-related symptoms in most patients.ConclusionsThis treatment, with demonstrated clinical activity with objective responses and prolonged disease control associated with disease-related symptom improvements, is an option as a salvage regimen for adult patients with recurrent ependymoma.  相似文献   
9.

Aims

Current treatments for the most common form of brain tumor, glioma, are disappointing in their effectiveness. Low expression levels of GART, an enzyme in the core nucleotide metabolism, significantly correlate with chemosensitivity, conferring a survival advantage to tumor cells. Our study aimed to explore the expression and function of GART in glioma.

Methods

Immunohistochemical and Western blot analysis were performed in 70 cases of human gliomas and normal brain tissues. We mainly used cell growth assay and multicellular tumor spheroid formation assay to evaluate the proliferation and chemosensitivity of glioma cells.

Results

High GART expression (most cancer cells cytoplasm stained) was observed in 70 specimens and was related to the grade of malignancy. We also reviewed each grade of tumors separately and investigated whether GART expression predicted patient survival within each subgroup. In brief, GART overexpression was significantly associated with overall survival (P = 0.03). Interestingly, transfecting cells with GART-siRNA suppressed proliferation and enhanced temozolomide (TMZ)-induced apoptosis in glioma cells.

Conclusion

The current results showed that GART expression was associated with glioma grade and that high GART protein expression might be related to poor outcome.  相似文献   
10.
目的比较替莫唑胺联合依托泊苷与单用替莫唑胺在成人高级别脑胶质瘤术后综合治疗中的疗效差异。方法 42例成人高级别脑胶质瘤患者行手术切除病灶,术后随机分为两组,单药组(单用替莫唑胺)和联合治疗组(替莫唑胺联合依托泊苷)。比较两组患者的无进展生存期及不良反应。结果单药组和联合治疗组的中位无进展生存时间分别为17.5周和24.4周,6个月无进展生存率分别为31.8%和45.0%。联合治疗组的无进展生存期和6个月无进展生存率均要明显高于单药组(均P0.05)。同时,两组患者的不良反应无显著差异。结论在成人高级别脑胶质瘤术后综合治疗中,替莫唑胺联合依托泊苷的化疗疗效要优于单用替莫唑胺治疗,该方案值得临床推广。  相似文献   
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