Bin Dai

Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan-Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management.

Simultaneous determination of six flavonoids from Paulownia tomentosa flower extract in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

Abstract A simple, rapid and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for simultaneous determination of six components including apigenin, quercetin, apigenin-7-O-β-d-glucoside, quercetin-3-O-β-d-glucoside, 3′-methoxyluteolin-7-O-β-d-glucoside, and tricin-7-O-β-d-glucopyranoside in rat plasma using formononetin as the internal standard (IS). The plasma samples were pretreated by a one-step liquid–liquid extraction with dichloromethane. The chromatographic separation was carried out on a ZORBAX SB-Aq column with a gradient mobile phase consisting of acetonitrile and 2mM aqueous ammonium acetate. All analytes and IS were quantitated through electrospray ionization in negative ion multiple reaction monitoring mode. The mass transitions were as follows: m/z 269.1→117.2 for apigenin, m/z 301.2→151.2 for quercetin, m/z 431.3→311.2 for apigenin-7-O-β-d-glucoside, m/z 463.2→300.2 for quercetin-3-O-β-d-glucoside, m/z 461.3→283.1 for 3′-methoxyluteolin-7-O-β-d-glucoside, m/z 491.3→313.1 for tricin-7-O-β-d-glucopyranoside, and m/z 267.2→252.2 for IS, respectively. All calibration curves exhibited good linearity with correlation coefficient (r)>0.995. The intra-day and inter-day precisions (RSD) at three QC levels were both less than 14.0% and the accuracies ranged from 89.8% to 113.8%. The extraction recoveries of six compounds ranged from 82.3% to 92.5%. The validated method was successfully applied to pharmacokinetic study of the six components in male rat plasma after oral administration of Paulownia tomentosa flower extract.

Upregulation of p-Smad2 contributes to FAT10-induced oncogenic activities in glioma

The human leukocyte antigen f-associated transcript 10 (FAT10) has a similar structure and function with ubiquitin, which efficiently mediate proteasome degradation in an ubiquitin-independent manner. FAT10 expression is upregulated in many tumor tissues and plays a vital role in cell cycle regulation and tumor genesis. However, its role in glioma has not been illuminated. The aim of this study was to evaluate the prognostic value of FAT10 and investigate its functional roles in glioma. The expression of FAT10 in glioma patient samples was examined using quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry methods. Glioma cell lines with either FAT10 overexpression or knockdown were created. The effect of FAT10 on glioma cell migration and invasion was investigated using these cells. In the present study, we had shown that FAT10 was elevated significantly in glioma samples and correlated with tumor pathological grade. FAT10 high-expression glioma is associated with a poor clinical prognosis. Overexpression of FAT10 promoted proliferation, invasion, migration, and sphere formation of glioma cells, whereas downregulation of FAT10 had an opposite effect. Overexpression of FAT10 also promoted the growth of glioma cells in vivo. Moreover, FAT10 enhanced the phosphorylation of Smad2, which contributes to FAT10-induced oncogenic activities in glioma. In conclusion, these findings indicate that FAT10 is a critical regulator potential therapeutic target of glioma.

Whole Course Neuroendoscopic Resection of Cerebellopontine Angle Epidermoid Cysts.

Background Epidermoid cysts are the third most common tumor of the cerebellopontine angle (CPA). Diagnosis often occurs after involvement of the sulci and cisterns that surround nerves and blood vessels, making complete resection highly challenging. Objective To determine the efficacy of whole course neuroendoscopic surgery in the management of CPA epidermoid cysts. Methods We performed a retrospective analysis of clinical data of 13 male and 17 female patients (mean age: 42.4 ± 11.4 years) who presented with a CPA epidermoid cyst and underwent whole course neuroendoscopy. Complications and tumor recurrence were assessed at follow-up. Results Clinical manifestations included an initial symptom of headache (n = 21), gait instability (n = 6), intracranial hypertension (n = 13), posterior cranial nerve symptoms (n = 6), ataxia (n = 5), and hydrocephalus (n = 1). All patients tolerated tumor resection with subsequent symptomatic improvement, and the results of the postoperative magnetic resonance imaging scan did not show any remnants of tumor. Mean duration of surgery was 2.61 ± 0.47 hours, mean loss of blood was 96.8 ± 35.4 mL, and the mean duration of hospitalization was 7.5 ± 2.25 days. Postoperative complications (8 of 30 [26.7%]) included fever (n = 5), communicating hydrocephalus (n = 1), facial nerve paralysis (n = 1), and abducens nerve palsy (n = 1). Tumor recurrence was observed in two patients (6.7%). No deaths or intracranial hemorrhage was reported. Conclusions The characteristics of epidermoid cysts make them amenable to whole course neuroendoscopic resection. Use of physiologic/pathologic interspaces and neuroendoscopic angulations decreases traction on the brain, improves complete resection rates, and decreases postoperative complications.

Neuroendoscopic Evaluation and Treatment for Cerebral Ventricular Infection

To the Editor: Cerebral ventricular infection (CVI), also termed ependymitis, involves an inflammatory response in the cerebral ventricular system. CVI is characterized by leukocytosis in the cerebrospinal fluid (CSF), a positive culture result of pathogenic bacteria, and imaging changes in the ventricles.[1] CVI mainly occurs after traumatic brain injury or surgery and is particularly prevalent in patients receiving external ventricular drainage (EVD) or a ventricular peritoneal shunt.[2] CVI is a serious complication after neurosurgery and can affect the prognosis and quality of life of patients. Therefore, early evaluation and treatment are critical for CVI patients. Herein, we report a retrospective study examining the role of neuroendoscopic evaluation and treatment for CVI over multiple medical centers in China.

Histone demethylase KDM5A inhibits glioma cells migration and invasion by down regulating ZEB1

Malignant gliomas are highly lethal cancers worldwide as tumor cells infiltrate to healthy brain tissue invariably. Histone demethylase KDM5A as an oncogene or tumor suppressor in cancer still has been controversial. KDM5A may have a different function in different type cancer cells. However, the specific roles of KDM5A in the progression of glioma remain undiscovered. In this study, we found that compared with primary glioma, metastasis glioma had low KDM5A levels. Besides, lower KDM5A levels were linked to poor survival in glioma cancer patients, indicating that KDM5A is a new prognostic marker for glioma cancer. KDM5A knockdown increases the invasive abilities of glioma cancer cells and changes the EMT markers. A mechanism, KDM5A suppressing the expression of ZEB1, and its catalytic activity is indispensable for anti-invasive function. Our study revealed that histone demethylase KDM5A exerts anti-invasiveness function partly through repressing oncogenic ZEB1 expression by mediating H3K4 demethylation. We also demonstrate that ZEB1 play a crucial role in KDM5A induced function. In summary, in this study, we showed that KDM5A has a crucial role in glioma and therefore may serve as a novel therapeutic target and prognostic marker in glioma.

Prognostic indicators of adult medullary gliomas after microsurgical treatment - A retrospective analysis of 54 patients.

Due to the low incidence of medullary gliomas, the special location, and the function of the gliomas in the medulla oblongata, microsurgical treatment is still challenging for neurosurgeons. The aim of this study was to observe the effect of microsurgical treatment of adult medullary gliomas and to explore the prognostic factors after treatment. The clinical data from 54 patients with adult medullary gliomas who received microsurgical treatment at Beijing Tiantan Hospital (China) from April 2008 to April 2014 was retrospectively analyzed. The factors affecting their prognosis were analyzed with log-rank univariate analysis. The factors that affected prognosis included age, gender, duration of preoperative symptoms, Karnofsky Performance Scale (KPS) score, World Health Organization (WHO) grade, extent of tumor resection, and postoperative complications. Those with statistical significance in the univariate analysis were entered into a multivariate Cox regression analysis. WHO grading showed 7 cases of grade I, 30 cases of grade II, 14 cases of grade III, and 3 cases of grade IV tumors. Univariable analysis showed that postoperative nasogastric feeding (P=0.031), WHO pathological grade (P=0.018), extent of resection (P=0.016), and preoperative involvement of ≥3 cranial nerves (CNs) (P=0.014) affected overall survival. The WHO pathological grade of the tumor was an independent risk factor for prognosis. In conclusion, the WHO pathological grade of the tumor was an important prognostic indicator.

Experience with Lumbar Puncture Following Endoscopic Third Ventriculostomy for Obstructive Hydrocephalus.

Background and Objective The increase in intracranial pressure (ICP) in some patients in the immediate postoperative period following endoscopic third ventriculostomy (ETV) is not well understood. This study explored the effect of lumbar puncture following ETV for obstructive hydrocephalus on outcome. Materials and Methods A total of 145 patients with obstructive hydrocephalus underwent ETV between 2009 and 2014. Following ETV, all patients underwent lumbar puncture on postoperative days 1 and 3. Results In 106 patients, ICP returned to normal levels accompanied by symptom relief. In 39 patients, ICP remained high on postoperative days 3, and lumbar puncture was continued every alternate postoperative day for 11 days. ICP always returned to normal. These 39 patients were divided into two groups for analysis: group A (age < 18 years) and group B (age ≥ 18 years). Peak values of ICP for groups A and B were recorded on days 3 and 5, respectively. Conclusions Our study suggests an important role for postoperative lumbar puncture in ensuring successful treatment results after ETV. In most of the symptomatic patients with obstructive hydrocephalus, lumbar puncture appears to contribute to rapid ICP normalization, to alleviation of symptoms, and prevention of complications.