Xi’an Zhang

Alpha-enolase as a potential cancer prognostic marker promotes cell growth, migration, and invasion in glioma

BackgroundThe success of using glycolytic inhibitors for cancer treatment relies on better understanding the roles of each frequently deregulated glycolytic genes in cancer. This report analyzed the involvement of a key glycolytic enzyme, alpha-enolase (ENO1), in tumor progression and prognosis of human glioma.MethodsENO1 expression levels were examined in glioma tissues and normal brain (NB) tissues. The molecular mechanisms of ENO1 expression and its effects on cell growth, migration and invasion were also explored by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, Transwell chamber assay, Boyden chamber assay, Western blot and in vivo tumorigenesis in nude mice.ResultsENO1 mRNA and protein levels were upregulated in glioma tissues compared to NB. In addition, increased ENO1 was associated disease progression in glioma samples. Knocking down ENO1 expression not only significantly decreased cell proliferation, but also markedly inhibited cell migration and invasion as well as in vivo tumorigenesis. Mechanistic analyses revealed that Cyclin D1, Cyclin E1, pRb, and NF-κB were downregulated after stable ENO1 knockdown in glioma U251 and U87 cells. Conversely, knockdown of ENO1 resulted in restoration of E-cadherin expression and suppression of mesenchymal cell markers, such as Vimentin, Snail, N-Cadherin, β-Catenin and Slug. Furthermore, ENO1 suppression inactivated PI3K/Akt pathway regulating the cell growth and epithelial-mesenchymal transition (EMT) progression.ConclusionOverexpression of ENO1 is associated with glioma progression. Knockdown of ENO1 expression led to suppressed cell growth, migration and invasion progression by inactivating the PI3K/Akt pathway in glioma cells.

Anatomic relations of the arachnoidea around the pituitary stalk: relevance for surgical removal of craniopharyngiomas

PurposeThe growth pattern of craniopharyngiomas (CP) is yet to be understood due to challenges arising from the diversity of morphological features that exist. This in turn has had implications on the development of safe surgical strategies for management of these lesions. The aim of this study is to propose a morphological classification of CP based on their tumor–membrane relationship. It is hoped that this will contribute to better understanding of CP morphology and prediction of the intraoperative classification.MethodsHistological techniques were used to study eight fetuses. Following Masson staining, the membranes around the pituitary stalk were observed under microscope. Pre-operative MRI and intraoperative images of 195 patients with CP were also analyzed.FindingsThe arachnoidal sleeve around the pituitary stalk (ASPS) was noted to be comprised of a compact fibrous component and a related loose trabecular component. The pituitary stalk was divided into four segments in accordance with the folds of the ASPS. Correspondingly, the growth of CPs was divided into four basic patterns—infra-diaphragmatic (ID), extra-arachnoidal (EA), intra-arachnoidal (IA) and sub-arachnoidal (SA) growth. The IA growth pattern can be further subdivided into two subtypes—namely, IA1 (with tumor growing within the fibrous component of the ASPS) and IA2 (with tumor growing within the trabecular component). This method of topographical division can be used to understand the growth of CP—infra-diaphragmatic CP show growth pattern ID or ID together with EA. Suprasellar CP can show an extra-ventricular growth pattern (EA or IA2), an extra- and intra-ventricular (IA2 + SA) growth pattern, a trans-infundibular growth pattern (ID + IA1 + SA) and an infundibulo-tuberal growth pattern (SA or SA + IA1). There is a statistically significant difference between CP growth patterns in children and adults. A predominance of ID growth is noted in children while adults tend to show a pattern of predominantly Extra-ventricular (EV) growth.ConclusionOur proposed classification details the relationship of the surrounding structures to CPs and purports to predict and identify the intraoperative anatomical stratification. It also attempts to help predict the growth patterns of these tumors. A knowledge of the intimate relations of the tumor and its key surrounding structures allows for safe surgical removal.

Intraventricular craniopharyngioma: morphological analysis and outcome evaluation of 17 cases

PurposeThere is still some confusion with regard to the tumor–third ventricle floor (3rd VF) relationship of craniopharyngiomas located exclusively within the third ventricle. This study aims to provide some evidence to clarify the growth pattern of intraventricular craniopharyngiomas (IVC), and to summarize the surgical strategy and outcome.MethodsSeventeen cases of IVC were reviewed retrospectively in relation to preoperative imaging, clinical presentation, intraoperative findings, tumor pathology, and surgical outcome. The tumor–3rd VF relationship and the tumors stratification were analyzed based on intraoperative inspection and histology.FindingsVariable adherence patterns of IVC to the 3rd VF were found, which were classified as (a) purely IVC with pedicle attachment to 3rd VF (two cases), (b) intra-3rd VF tumors with wide-based attachment but a dissectible tumor boundary (seven cases), and (c) intra-3rd VF tumors with an undissectible wide, tight attachment (eight cases). Histological analysis revealed that both of the two cases with growth pattern “a” intruded into the third ventricular cavity without a covering layer of neural tissue (which only exists in the squamous-papillary subtype). Tumors with growth pattern “b” and “c,” in contrast, were noted to have a thin layer of neural tissue. This occurred in both subtypes (11 adamantinomatous, 4 papillary). Total removal was accomplished in all tumors demonstrating growth pattern “a” and “b.” There was also better preservation of the 3rd VF and consequently a better outcome. On the other hand, total removal was only achieved in 50% of tumors showing growth pattern “c” including one mortality. No recurrence has been encountered in patients whose tumors were totally removed.ConclusionVariable adherence patterns and tumor subtypes were observed in IVCs, which were correlated to the tumor pathology, resectability, and subsequent prognosis.

Pneumatization of the sphenoid sinus in Chinese: the differences from Caucasian and its application in the extended transsphenoidal approach.

In recent years, the transsphenoidal approach has been extensively used surgically to treat parasellar, suprasellar, clival, and even petrous lesions. Extended pneumatization of the sphenoid sinus (SS) is considered an indispensable element for the extended transsphenoidal (ETS) approach. Because most anatomical studies of the ETS approach use Caucasian subjects, the present study aims to clarify the pneumatic extension types in Chinese individuals as well as any differences from those in Caucasians and analyze these differences with respect to the application of the ETS approach. A total of 200 computed tomography (CT) images of SSs and 18 adult cadaveric heads were selected for observation and measurement. The conchal, presellar, and sellar types comprised 6, 28.5, and 65.5% of subjects, respectively; according to the extra extension, the prevalence of the lateral, clival, lesser wing, and combined extension sinus types was 11.4, 21.4, 0.8, and 48.1% of subjects, respectively. The percentages of pneumatization of the anterior and posterior clinoid processes, pterygoid process, and optic strut were 5.0, 1.0, 22.3, and 7.0%, respectively. Onodi cells were observed in 61.1% of the sides of the cadaveric heads, including 30.6% with good pneumatization with identifiable optical or ICA bulges. These features were related to poor lateral and clival gasification in Chinese compared with Caucasians, which might make extended surgery more dangerous. However, the anterior pneumatization, especially the higher presentation of Onodi cells, ensures that the anterior ETS approach can be performed safely in Chinese patients. In general, measurements showing smaller sinus volumes and thicker bones with identifiable bone landmarks that are hard to find compared with those in Caucasians suggest increased surgical risks in the Chinese population. In this situation, carefully analysis of presurgical CT and magnetic resonance imaging scans is important. Furthermore, in the ETS approach, the use of stricter intraoperative technological devices such as neuronavigation and ultrasound Doppler is advisable.

The impact of the site of origin and rate of tumour growth on clinical outcome in children with craniopharyngiomas

Objectives  Data on many predictors of hypothalamic–pituitary axis dysfunction associated with childhood craniopharyngioma (CP) are rather inconsistent, probably reflecting the variable but as yet unclarified growth pattern of these tumours. The aim of this study was to define the determinative role of tumour growth pattern on hypothalamic–pituitary axis function and outcomes for childhood CPs.

Anatomical Study of the Arachnoid Envelope Over the Pineal Region

BACKGROUND The distribution of the arachnoid membrane and its relationship with the neurovascular structures in the pineal region are still not fully understood. OBJECTIVE Because the arachnoid membrane has an intimate relationship with the neurovascular structures in the pineal region and it will always be encountered surgically, we attempted to clarify the formation and distribution of the arachnoid envelope over the pineal region (AEPG). METHODS The formation and distribution of the AEPG and its relationship with the neurovascular structures in the pineal region were examined by anatomic dissection in 20 adult cadaveric formalin-fixed heads. RESULTS The supratentorial and infratentorial outer arachnoid membranes converged at the tentorial apex and then embraced and ran forward along the vein of Galen to form the AEPG. The AEPG could be divided into 2 parts. Typically, the posterior part of the AEPG enveloped the vein of Galen and the terminal segments of its tributaries, and the anterior part of the AEPG enveloped the suprapineal recess, the pineal gland, and the distal segment of the internal cerebral veins. The compartment demarcated by the AEPG did not communicate with the adjacent subarachnoid cisterns or space. CONCLUSION Previous knowledge about the AEPG, as well as the superior boundary and the contents of the quadrigeminal cistern, needs to be revised. The arrangement and individual variation of AEPG are important for a better understanding of the various growth patterns of the pineal tumors and the relationship between the tumor and the neurovascular structures in the pineal region.

Hypoxia-induced PLOD2 promotes proliferation, migration and invasion via PI3K/Akt signaling in glioma

Gliomas are the most common form of malignant primary brain tumors with poor 5-year survival rate. Dysregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was observed in gliomas, but the specific role and molecular mechanism of PLOD2 in glioma have not been reported yet. In this study, PLOD2 was found to be frequently up-regulated in glioma and could serve as an independent prognostic marker to identify patients with poor clinical outcome. Knockdown of PLOD2 inhibited proliferation, migration and invasion of glioma cells in vitro and in vivo. Mechanistically, inhibition of PLOD2 inactivated PI3K/AKT signaling pathway and thus regulated the expression of its downstream epithelial–mesenchymal transition (EMT)-associated regulators, including E-cadherin, vimentin, N-cadherin, β-catenin, snail and slug in glioma cells. Moreover, PLOD2 could be induced by hypoxia-inducible factor-1α (HIF-1α) via hypoxia, thereby promoting hypoxia-induced EMT in glioma cells. Our data suggests that PLOD2 may be a potential therapeutic target for patients with glioma.

A complex mechanism for HDGF-mediated cell growth, migration, invasion, and TMZ chemosensitivity in glioma

HDGF is overexpressed in gliomas as compared to normal brain. We therefore analyzed the molecular mechanisms of HDGF action in gliomas. HDGF was downregulated in normal brain tissue as compared to glioma specimens at both the mRNA and the protein levels. In glioma samples, increased HDGF expression was associated with disease progression. Knocking down HDGF expression not only significantly decreased cellular proliferation, migration, invasion, and tumorigenesis, but also markedly enhanced TMZ-induced cytotoxicity and apoptosis in glioma cells. Mechanistic analyses revealed that CCND1, c-myc, and TGF-β were downregulated after stable HDGF knockdown in the U251 and U87 glioma cells. HDGF knockdown restored E-cadherin expression and suppressed mesenchymal cell markers such as vimentin, β-catenin, and N-cadherin. The expression of cleaved caspase-3 increased, while Bcl-2 decreased in each cell line following treatment with shHDGF and TMZ, as compared to TMZ alone. Furthermore, RNAi-based knockdown study revealed that HDGF is probably involved in the activation of both the PI3K/Akt and the TGF-β signaling pathways. Together, our data suggested that HDGF regulates glioma cell growth, apoptosis and epithelial–mesenchymal transition (EMT) probably through the Akt and the TGF-β signaling pathways. These results provide evidence that targeting HDGF or its downstream targets may lead to novel therapies for gliomas.

Determining an Optimal Cutoff of Serum β-Human Chorionic Gonadotropin for Assisting the Diagnosis of Intracranial Germinomas

Background Beta (β)-human chorionic gonadotropin (β-HCG) is used to confirm the diagnosis and plan treatment of intracranial germinomas. However, the cutoff values of serum β-HCG in diagnosis of intracranial germinomas reported in the literature are inconsistent. To establish an appropriate cutoff value of serum β-HCG for diagnosis of intracranial germinomas, we retrospectively reviewed the records of intracranial tumor patients who received serum β-HCG and α-fetoprotein (AFP) tests for diagnostic purposes at our hospital from 2005 to 2014. Methods A total of 93 intracranial germinomas and 289 intracranial non-germ cell tumors were included in this study. Receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of 3 cutoffs (0.1, 0.4, and 0.5 mIU/mL) for diagnosing intracranial germinomas. The serum β-HCG level of intracranial germinoma patients was further analyzed to investigate the effect of metastasis status and tumor location on serum β-HCG level. Results The area under the ROC curve was 0.81 (P < .001), suggesting β-HCG is an effective marker. Of the 3 cutoff values, 0.1 mIU/mL possessed a highest sensitivity (66.67%) and good specificity (91%). Although there was no β-HCG level difference between metastatic and non-metastatic intracranial germinoma patients, the diagnostic rate of metastatic neurohypophyseal germinomas was significantly higher than that of its non-metastatic counterpart (P < .05), implying that the location of the germinoma might need to be considered when β-HCG is used as a marker to predict metastasis. Conclusions Determining an optimal cutoff of serum β-HCG is helpful for assisting the diagnosis of intracranial germinoma.

Growth and weight of children with craniopharyngiomas based on the tumour location and growth pattern

This study aimed to characterise the weight and growth of children with craniopharyngiomas and to analyse the role of the tumour location and growth pattern in the development of obesity and growth retardation in these children. We retrospectively analysed the records of 109 consecutive children with primary craniopharyngiomas. The patients were divided into two subgroups according to the location of the tumour: intrasellar (Group A); and the floor of the third ventricle (Group B). Height and body mass index were measured at standardised ages and at time points before, after, and at the time of diagnosis. Endocrinological and hypothalamic measurements before and after surgery were compared. Reduced growth rates occurred in early infancy and persisted until diagnosis in Group A, but were only present from age 5-6 in Group B. Therefore, reduced growth rates occur early in the history of intrasellar tumours, whereas rapid postoperative weight gain invariably occurs in patients with third ventricle tumours, which is a significant predictive factor for severe long term obesity in patients with childhood craniopharyngiomas.