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LCK expression is a potential biomarker for distinguishing primary central nervous system lymphoma from glioblastoma multiforme.

LCK 表达是鉴别原发性中枢神经系统淋巴瘤和多形性胶质母细胞瘤的潜在生物标志物。

  • 影响因子:2.01
  • DOI:10.1002/2211-5463.12849
  • 作者列表:"Ge L","Xu L","Lu S","Yan H
  • 发表时间:2020-03-31

:Glioblastoma multiforme (GBM) and primary central nervous system lymphoma (PCNSL) are both malignant cerebral tumors; however, their treatments are vastly different. Early and precise diagnosis is vital for subsequent adequate treatment to improve prognosis. Reliable biomarkers that can easily distinguish GBM and PCNSL are urgently needed. We evaluated the diagnostic potential of lymphocyte-specific protein tyrosine kinase (LCK) as a biomarker in differentiating PCNSL from GBM using established computational approaches (GEPIA, TCPA, TIMER, GEO, Oncomine) and immunohistochemistry. The results showed that LCK was expressed at a high level in PCNSL patients but at a low level in GBM patients. Moreover, LCK expression positively correlated with the levels of infiltrating B cells in diffuse large B-cell lymphoma (DLBC) and GBM. Overall, bioinformatics analysis and immunohistochemistry revealed that LCK expression is a potential biomarker for distinguishing PCNSL from GBM.


多形性胶质母细胞瘤 (GBM) 和原发性中枢神经系统淋巴瘤 (PCNSL) 都是恶性脑肿瘤; 然而,它们的治疗方法有很大的不同。早期和精确的诊断对于后续适当的治疗以改善预后至关重要。迫切需要易于区分 GBM 和 PCNSL 的可靠生物标志物。我们使用已建立的计算方法 (GEPIA 、 TCPA 、 TIMER 、 GEO 、 Oncomine) 评估了淋巴细胞特异性蛋白酪氨酸激酶 (LCK) 作为区分 PCNSL 和 GBM 的生物标志物的诊断潜力和免疫组化。结果表明,LCK 在 PCNSL 患者中表达水平较高,而在 GBM 患者中表达水平较低。此外,在弥漫性大 b细胞淋巴瘤 (DLBC) 和 GBM 中,LCK 表达与浸润 b细胞水平呈正相关。总体而言,生物信息学分析和免疫组织化学揭示 LCK 表达是区分 PCNSL 和 GBM 的潜在生物标志物。



作者列表:["Tiwari V","Mashimo T","An Z","Vemireddy V","Piccirillo S","Askari P","Hulsey KM","Zhang S","de Graaf RA","Patel TR","Pan E","Mickey BE","Maher EA","Bachoo RM","Choi C"]

METHODS:PURPOSE:To generate a preclinical model of isocitrate dehydrogenase (IDH) mutant gliomas from glioma patients and design a MRS method to test the compatibility of 2-hydroxyglutarate (2HG) production between the preclinical model and patients. METHODS:Five patient-derived xenograft (PDX) mice were generated from two glioma patients with IDH1 R132H mutation. A PRESS sequence was tailored at 9.4 T, with computer simulation and phantom analyses, for improving 2HG detection in mice. 2HG and other metabolites in the PDX mice were measured using the optimized MRS at 9.4 T and compared with 3 T MRS measurements of the metabolites in the parental-tumor patients. Spectral fitting was performed with LCModel using in-house basis spectra. Metabolite levels were quantified with reference to water. RESULTS:The PRESS TE was optimized to be 96 ms, at which the 2HG 2.25 ppm signal was narrow and inverted, thereby leading to unequivocal separation of the 2HG resonance from adjacent signals from other metabolites. The optimized MRS provided precise detection of 2HG in mice compared to short-TE MRS at 9.4 T. The 2HG estimates in PDX mice were in excellent agreement with the 2HG measurements in the patients. CONCLUSION:The similarity of 2HG production between PDX models and parental-tumor patients indicates that PDX tumors retain the parental IDH metabolic fingerprint and can serve as a preclinical model for improving our understanding of the IDH-mutation associated metabolic reprogramming.

来源期刊:BMC cancer
作者列表:["Ang SYL","Lee L","See AAQ","Ang TY","Ang BT","King NKK"]

METHODS:BACKGROUND:Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population. METHODS:Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients' age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test. RESULTS:181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006). CONCLUSIONS:The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.

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作者列表:["Abbruzzese C","Matteoni S","Persico M","Villani V","Paggi MG"]

METHODS:BACKGROUND:Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. Tumor recurrence occurs in virtually all cases, therefore, despite any treatment, the median survival is very low (14.6 months), which makes the approach to these patients a challenging clinical issue. MAIN BODY:The escalating costs and times required for new medications to reach the bedside make repurposing or repositioning of old drugs, when scientific bases allow their use in other pathologies, an appealing strategy. Here, we analyze a number of literature data concerning the antipsychotic chlorpromazine, the founder of the phenothiazines class of drugs, a medication widely used in the clinics for approximately 60 years. The drug exerts its effects on psychiatric patients by interfering with the dopamine receptor D2, although more recent pharmacodynamics studies ascribe chlorpromazine a series of biological effects on cancer cells, all converging in hindering also glioblastoma survival capabilities. SHORT CONCLUSIONS:On these bases, and assisted by the information on the well-established chlorpromazine toxicity and dosage in humans, we designed a Phase II clinical trial involving the combination of chlorpromazine with the standard treatment, temozolomide, in the adjuvant phase of the therapeutic protocol. Patients displaying hypo-methylation of the MGMT gene, and thus intrinsically resistant to temozolomide, will be enrolled. The endpoints of this study are the analysis of toxicity and clinical activity, as evaluated in terms of Progression-Free Survival, of the association of chlorpromazine with the first-line treatment for this very serious form of cancer.

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