Pediatric WNT medulloblastoma predisposition in intraoperative blood loss: a retrospective observational cohort study.

Introduction: Molecular subgroups influence the vascular architecture within medulloblastomas, particularly the wingless (WNT) subgroup, which contributes to its propensity for primary tumor hemorrhage. Whether this mechanism affects intraoperative blood loss remains unknown. This study aimed to assess the association between WNT medulloblastoma and the predisposition for blood loss. Methods: This was a retrospective observational study using data from a neuro-oncology center comprising molecular data on patients treated between December 31, 2014, and April 30, 2023. Differences between WNT and other subgroups in the risk of primary outcome-intraoperative blood loss were assessed using multivariable-adjusted linear regression. Results: Of the 148 patients included in the analysis, 18 patients (12.2%) had WNT, 42 (28.4%) had sonic hedgehog (SHH) TP53-wildtype, 7 (4.7%) had SHH TP53-mutant, and 81 (54.7%) were non-WNT/ non-SHH. The WNT subgroup more frequently underwent primary intratumoral hemorrhage (22% vs. 3.8%; p = 0.011). The median intraoperative blood loss was 400.00 (interquartile range [IQR] 250, 500) mL for WNT and 300.00 [200, 400] mL for the other subgroups (p = 0.136), with an adjusted ß of 135.264 (95% confidence intervals [CI], 11.701-258.827; p = 0.032). Similar results were observed in both midline and noninfiltrative margin medulloblastoma. Discussion: WNT medulloblastoma is typically associated with primary intratumoral hemorrhage and intraoperative blood loss. The validity of determining the surgical approach based on predicted molecular subtypes from imaging data is questionable. However, attempting to engage in risk communication with patients in a molecular-specific way is worthwhile to validate.

Neurosurgical short-term outcomes for pediatric medulloblastoma patients and molecular correlations: a 10-year single-center observation cohort study.

This study examined the risk factors for short-term outcomes, focusing particularly on the associations among molecular subgroups. The analysis focused on the data of pediatric patients with medulloblastoma between 2013 and 2023, as well as operative complications, length of stay from surgery to adjuvant treatment, 30-day unplanned reoperation, unplanned readmission, and mortality. 148 patients were included. Patients with the SHH TP53-wildtype exhibited a lower incidence of complications (45.2% vs. 66.0%, odds ratio [OR] 0.358, 95% confidence interval [CI] 0.160 - 0.802). Female sex (0.437, 0.207 - 0.919) was identified as an independent protective factor for complications, and brainstem involvement (1.900, 1.297 - 2.784) was identified as a risk factor. Surgical time was associated with an increased risk of complications (1.004, 1.001 - 1.008), duration of hospitalization (1.006, 1.003 - 1.010), and reoperation (1.003, 1.001 - 1.006). Age was found to be a predictor of improved outcomes, as each additional year was associated with a 14.1% decrease in the likelihood of experiencing a prolonged length of stay (0.859, 0.772 - 0.956). Patients without metastasis exhibited a reduced risk of reoperation (0.322, 0.133 - 0.784) and readmission (0.208, 0.074 - 0.581). There is a significant degree of variability in the occurrence of operative complications in pediatric patients with medulloblastoma. SHH TP53-wildtype medulloblastoma is commonly correlated with a decreased incidence of complications. The short-term outcomes of patients are influenced by various unmodifiable endogenous factors. These findings could enhance the knowledge of onconeurosurgeons and alleviate the challenges associated with patient/parent education through personalized risk communication. However, the importance of a dedicated center with expertise surgical team and experienced neurosurgeon in improving neurosurgical outcomes appears self-evident.

Prognostic Value of miR-137 in Children with Medulloblastoma and its Regulatory Effect on Tumor Progression.

Medulloblastoma is a malignant tumor with high incidence and poor prognosis in adolescents and children. MicroRNA-137 (miR-137) has been found to be abnormally expressed in cancers such as pancreatic cancer. The purpose of this study is to explore the expression of miR-137 in MB and its role in cell physiological activities to determine the significance of miR-137 in the prognosis of MB. First, the expression of miR-137 in MB tissues and cell lines was analyzed by qRT-PCR. Then the Kaplan-Meier survival curve was used to analyze the significance of miR-137 expression in the prognosis, and the Cox regression model was used to explore the correlation between miR-137 expression and clinical characteristics. The effects of miR-137 on MB cell activities were analyzed by MTT assay, Transwell assays, and flow cytometry. It can be concluded from the results that the expression of miR-137 is down-regulated in MB tissues and cells. The down-regulation of miR-137 was significantly related to the poor prognosis of MB, and significantly related to clinical indicators. Up-regulated miR-137 inhibited cell proliferation, migration, invasion, and cell cycle progression, as well as induced cell apoptosis by targeting KDM1A. This study can conclude that miR-137 may be used as a prognostic biomarker of MB.

Circulating miR-27b as a Biomarker of the Development and Progression of Carotid Artery Stenosis.

OBJECTIVE: A close relationship of microRNAs (miRNAs) with various human diseases has been widely reported, including cardiovascular disease. The current study attempted to examine the abnormal expression of miR-27b in asymptomatic carotid artery stenosis (ACAS), its diagnostic value and predictive value for the development of ACAS were also assessed. METHODS: Clinical serum samples were collected from both ACAS patients and healthy individuals, and levels of miR-27b in the clinical samples were detected using Real-time quantitative PCR. Cerebral ischemia events (CIEs) of patients during the 5-year follow-up were collected. The diagnostic and predictive values of serum miR-27b was assessed via plotting Receiver operating characteristic (ROC) and Kaplan-Meier curves. Multivariate cox regression analysis was performed for clinical independent index analysis. RESULTS: ACAS patients had higher levels of miR-27b than the healthy subjects. There were close association of serum miR-27b levels with total cholesterol (TC) level, absence of hypertension and degree of carotid stenosis. High levels of miR-27b could differentiate ACAS cases from healthy subjects, and predicted the high incidence of CIEs. MiR-27b could be used as an independent predictor of cerebrovascular events via multiple Cox regression analysis (P = .031). CONCLUSION: The high level of miR-27b can predict the occurrence of ACAS, and is closely related to the subsequent occurrence of CIEs. The present results provide evidence for circulating miR-27b as a diagnostic and prognostic marker in patients with ACAS.

EZH2 regulates the malignancy of human glioblastoma cells via modulation of Twist mRNA stability.

Glioblastoma multiforme (GBM) is a lethal primary brain tumor with poor survival lifespan and dismal outcome. However, the effects and mechanisms of epigenetic factors on the development of GBM were still not well illustrated. We found that expression of enhancer of zeste homolog 2 (EZH2), which can catalyze histone H3K27me3 to modulate gene expression, was increased in GBM cells. Knockdown of EZH2 can suppress proliferation and migration, while increase temozolomide (TMZ) sensitivity, of GBM cells. Further, knockdown of EZH2 or its specific inhibitor GSK126 can decrease expression of Twist, while over expression of Twist can reverse si-EZH2-suppressed malignancy of GBM cells. Mechanistically, EZH2 can positively regulate mRNA stability of Twist1 mRNA. Further, miR-206, which can bind with 3'UTR of Twist1 mRNA, was involved in EZH2-regulated mRNA stability of Twist1. Collectively, our data suggest that EZH2 might be a potential target for GBM treatment. Further, miR-206/Twist axis is involved in EZH2-regulated malignancy of GBM cells.

Effects of Urtica dioica extract on malignant biological behaviors of breast cancer cells and its possible mechanism / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨大荨麻提取物对乳腺癌细胞增殖、凋亡和细胞周期的影响，并初步探讨其可能的作用机制。方法：用不同质量浓度的大荨麻提取物（0、1、2、4、8、16、32、64 mg/ml）处理乳腺癌细胞MCF-7和MDA-MB-231 24 h，MTT法检测细胞增殖活力，选择中位抑制浓度附近的浓度（5和10 mg/ml）作为给药浓度分别处理MCF-7和MDA-MB-231细胞24 h后，平板克隆形成实验和流式细胞术分别检测大荨麻提取物对乳腺癌细胞增殖、周期和凋亡的影响，WB法检测对细胞周期和凋亡相关蛋白以及PI3K/AKT信号通路相关蛋白表达的影响。在MCF-7细胞用5 mg/ml大荨麻提取物处理的同时转染过表达AKT质粒（大荨麻+AKT组），转染空载质粒为对照组（大荨麻+vec组），WB法检测过表达效率，比较过表达AKT对细胞增殖、周期和凋亡的影响。结果：各大荨麻提取物处理组MCF-7和MDA-MB-231细胞增殖活力均显著低于对照组（P<0.05或P<0.01）；与对照组比较，5或10 mg/ml大荨麻处理组乳腺癌细胞的克隆形成数显著减少，G0/G1期细胞占比和凋亡率显著增加（P<0.05或P<0.01），P21、BAX蛋白表达显著升高而Cyclin D1、CDK4、Bcl2蛋白以及p-PI3K、p-AKT蛋白表达显著降低（P<0.05或P<0.01）。大荨麻+AKT组p-AKT和AKT蛋白表达显著高于大荨麻+vec组，克隆数、S期和G2/M期细胞占比均高于大荨麻+vec组（P<0.05或P<0.01），G0/G1期细胞占比和凋亡率低于大荨麻+vec组（P<0.05或P<0.01）。结论：大荨麻提取物可以抑制乳腺癌细胞增殖、促进凋亡且阻滞细胞在G0/G1期，其作用机制可能与抑制PI3K/AKT信号通路相关。

Ubiquitin-specific protease 4 promotes glioblastoma multiforme via activating ERK pathway.

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most common brain tumors in adults. Current treatments cannot increase survival to a large extent, as the glioblastoma development mechanisms remain unknown. It has been well documented that ubiquitination contributes to tumor initiation and/or progression in many kinds of cancer. Ubiquitin-specific protease 4 (USP4), a member of deubiquitinating enzymes (DUBs) family, can remove ubiquitin residues and play a role in cancer development. METHODS: In the current study, lentiviruses were used to manipulate the expression of USP4. Real-time PCR and Western blot were used to measure the expression level of USP4. Then, CCK-8 and annexin-V staining were used to detect cell proliferation and cell apoptosis, respectively. RESULTS: First, we found that USP4 was highly upregulated in GBM tissues in comparison with that in normal tissues and high level of USP4 correlated with poor prognosis. Moreover, knockdown of USP4 could significantly inhibit cell proliferation and increase cell apoptosis in U87 and T98G cells. Cells with stable USP4 reduction exhibited slower tumor growth rate and smaller tumor size than the control group cells in a xenograft mouse model. Inhibition of USP4 downregulated the expression of PCNA, Bcl-2 and p-ERK1/2, but upregulated the expression of Bax both in vitro and in vivo. Inversely, USP4 overexpression could attenuate the effects contributed by ERK inhibitor. TGF-ßR inhibition reduced level of TGF-ßR1, p-smad2 and p-ERK1/2 which can partially be rescued by USP4 overexpression. CONCLUSION: USP4, as a potential novel oncogene, promotes GBM by activation of ERK pathway through regulating TGF-ß.

[Management of obstructive hydrocephalus before posterior fossa tumor resection in children].

OBJECTIVE: To explore the management of obstructive hydrocephalus caused by posterior fossa tumors before tumor resection in children. METHODS: The clinical data were reviewed of 162 pediatric patients of posterior fossa tumors with obstructive hydrocephalus undergoing surgical tumor removal between January 2008 and June 2012. Ninety children received preoperative Ommaya external drainage (group A) and 72 underwent preoperative ventriculo-peritoneal shunting (V-Ps) (group B). The therapeutic effects were evaluated and compared between the two groups. RESULTS: Postoperative complications found in a total of 67 cases including infection (27), shunt blockage (19), subdural hematoma or effusion (16), ventricle fissure syndrome (5), and tumor hernia (4). Significant differences were found in the incidences of shunt blockage (P=0.047) and subdural hematoma or effusion (P=0.039) but not in the incidences of intracranial infection (P=0.478) or tumor hernia (P=0.462) between the two groups. CONCLUSION: Ommaya reservoir can produce good results through simple surgical procedures for treatment of acute hydrocephalus in children with posterior fossa tumors and is associated less trauma and complications.

Qualitative and quantitative analysis of anthraquinones in rhubarbs by high performance liquid chromatography with diode array detector and mass spectrometry.

Rhubarb is well known in traditional Chinese medicines (TCMs) mainly due to its effective purgative activity. Anthraquinones, including anthraquinone derivatives and their glycosides, are thought to be the major active components in rhubarb. To improve the quality control method of rhubarb, we studied on the extraction method, and did qualitative and quantitative analysis of widely used rhubarbs, Rheum tanguticum Maxim. ex Balf. and Rheum palmatum L., by HPLC-photodiode array detection (HPLC-DAD) and HPLC-mass spectrum (HPLC-MS) on a Waters SymmetryShield RP18 column (250 mm × 4.6 mm i.d., 5 µm). Amount of five anthraquinones was viewed as the evaluating standard. A standardized characteristic fingerprint of rhubarb was provided. From the quantitative analysis, the rationality was demonstrated for ancestors to use these two species of rhubarb equally. Under modern extraction methods, the amount of five anthraquinones in Rheum tanguticum Maxim. ex Balf. is higher than that in Rheum palmatum L. Among various extraction methods, ultrasonication with 70% methanol for 30 min is a promising one. For HPLC analysis, mobile phase consisted of methanol and 0.1% phosphoric acid in water with a gradient program, the detection wavelength at 280nm for fingerprinting analysis and 254 nm for quantitative analysis are good choices.