Pu-Cha Jiang

Upregulation of SATB1 is associated with the development and progression of glioma

BackgroundSpecial AT-rich sequence-binding protein-1 (SATB1) has been reported to be expressed in several human cancers and may have malignant potential. This study was aimed at investigating the expression and potential role of SATB1 in human glioma.MethodThe relationship between SATB1 expression, clinicopathological parameters, Ki67 expression and MGMT promoter methylation status was evaluated, and the prognostic value of SATB1 expression in patients with gliomas was analyzed. SATB1-specific shRNA sequences were synthesized, and U251 cells were transfected with SATB1 RNAi plasmids. Expression of SATB1 mRNA and protein was investigated by RT-PCR and immunofluoresence staining and western blotting. The expression of c-Met, SLC22A18, caspase-3 and bcl-2 protein was determined by western blotting. U251 cell growth and adherence was detected by methyl thiazole tetrazolium assay. The apoptosis of U251 cells was examined with a flow cytometer. The adherence, invasion, and in vitro angiogenesis assays of U251 cells were done. The growth and angiogenesis of SATB1 low expressing U251 cells was measured in an in vivo xenograft model.ResultsOf 70 tumors, 44 (62.9%) were positive for SATB1 expression. SATB1 expression was significantly associated with a high histological grade and with poor survival in univariate and multivariate analyses. SATB1 expression was also positively correlated with Ki67 expression but negatively with MGMT promoter methylation in glioma tissues. SATB1 shRNA expression vectors could efficiently induce the expression of SLC22A18 protein, increase the caspase-3 protein, inhibit the expression of SATB1, c-Met and bcl-2 protein, the growth, invasion, metastasis and angiogenesis of U251 cells, and induce apoptosis in vitro. Furthermore, the tumor growth of U251 cells expressing SATB1 shRNA were inhibited in vivo, and immunohistochemical analyses of tumor sections revealed a decreased vessel density in the animals where shRNA against SATB1 were expressed.ConclusionsSATB1 may have an important role as a positive regulator of glioma development and progression, and that SATB1 might be a useful molecular marker for predicting the prognosis of glioma.

Correlation of low SLC22A18 expression with poor prognosis in patients with glioma.

We investigated the expression of the putative tumor suppressor SLC22A18 to evaluate it as a prognostic marker in glioma patients. Immunohistochemical and Western blot analyses of clinical tissue samples obtained from 120 patients with glioma were performed. Low expression of SLC22A18 was observed in 71.7% of patients. Loss of SLC22A18 expression in glioma was significantly related to pathological grade (p = 0.003). High pathological grade (World Health Organization III-IV) was correlated with negative (low or absent) expression of SLC22A18, which was correlated with a significantly shorter overall patient survival than in those with positive (high) expression (p = 0.007). Multivariate Cox regression analysis indicated that SLC22A18 expression level is an independent survival prognostic factor for patients with glioma (p = 0.011). Western blotting analysis confirmed decreased expression of SLC22A18 in glioma tissues compared with adjacent brain tissues. This study suggests that SLC22A18 functions as a tumor suppressor in glioma and represents a candidate biomarker for long-term survival in this disease.

Promoter methylation and downregulation of SLC22A18 are associated with the development and progression of human glioma

BackgroundDownregulation of the putative tumor suppressor gene SLC22A18 has been reported in a number of human cancers. The aim of this study was to investigate the relationship between SLC22A18 downregulation, promoter methylation and the development and progression of human glioma.MethodSLC22A18 expression and promoter methylation was examined in human gliomas and the adjacent normal tissues. U251 glioma cells stably overexpressing SLC22A18 were generated to investigate the effect of SLC22A18 on cell growth and adherence in vitro using the methyl thiazole tetrazolium assay. Apoptosis was quantified using flow cytometry and the growth of SLC22A18 overexpressing U251 cells was measured in an in viv o xenograft model.ResultsSLC22A18 protein expression is significantly decreased in human gliomas compared to the adjacent normal brain tissues. SLC22A18 protein expression is significantly lower in gliomas which recurred within six months after surgery than gliomas which did not recur within six months. SLC22A18 promoter methylation was detected in 50% of the gliomas, but not in the adjacent normal tissues of any patient. SLC22A18 expression was significantly decreased in gliomas with SLC22A18 promoter methylation, compared to gliomas without methylation. The SLC22A18 promoter is methylated in U251 cells and treatment with the demethylating agent 5-aza-2-deoxycytidine increased SLC22A18 expression and reduced cell proliferation. Stable overexpression of SLC22A18 inhibited growth and adherence, induced apoptosis in vitro and reduced in vivo tumor growth of U251 cells.ConclusionSLC22A18 downregulation via promoter methylation is associated with the development and progression of glioma, suggesting that SLC22A18 is an important tumor suppressor in glioma.

Antisense oligonucleodes targeting the focal adhesion kinase inhibit proliferation, induce apoptosis and cooperate with cytotoxic drugs in human glioma cells

SummaryTo examine the role of focal adhesion kinase in human glioma cells, we studied its effects on proliferation and apoptosis using FAK antisense oligonucleotide. U251 MG cells were transfected with ODNs, sense FAK, mismatch FAK and antisense-FAK, respectively. Expression of FAK proteins were detected by Western blots and Immnofluoressence. Cell apoptosis and mitochondrial membrane potential were analyzed by flow cytometry. Caspase-3 activity was measured by spectrofluorometer. MTT assay was used to examine changes in cell proliferation. The protein expression of FAK in U251 MG cells decreased in antisense-FAK ODNs group significantly. Caspase-3 activity increased in cells treated with antisense-FAK and down-regulated when treated with caspase-3 inhibitor. The level of cell apoptosis and loss of mitochondrial membrane potential in antisense-FAK group was higher than in the mismatch sense group. Cells proliferation was inhibited by antisense-FAK, and the effects were clearly additive when antisense oligonuceotides were added to cells treated with the anticancer agents. The results suggest that antisense-FAK ODNs inhibit U251 MG cells proliferation and induce their apoptosis. It is possible that FAK via mitochondrial and caspase-3 inhibits U251 MG cells apoptosis. And antisense oligonucleotide treatment enhances U251 MG cells sensitivity to chemotherapy.

Relationship between SATB1 expression and prognosis in astrocytoma

Special AT-rich-sequence-binding protein 1 (SATB1), a new type of gene regulator, has been reported to be expressed in various human cancers and may be associated with malignancy. The aim of this study was to investigate the expression of SATB1 in astrocytoma and to determine its prognostic value for the overall survival of patients with astrocytoma. The expression of SATB1 protein and messenger RNA (mRNA) in human astrocytoma specimens was examined using immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The relationship between SATB1 expression and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was also investigated. Spearmans correlation coefficient was used to describe the association between SATB1 expression and the clinical parameters of astrocytoma patients. SATB1 protein and mRNA were expressed at significant levels in astrocytoma specimens. SATB1 expression was positively correlated with astrocytoma pathological grade but negatively correlated with the life span of astrocytoma patients. SATB1 expression was also significantly lower in astrocytoma specimens with MGMT promoter methylation than in those without MGMT promoter methylation. Our findings suggest that SATB1 may have an important role as a positive regulator of astrocytoma development and progression and that SATB1 might be a useful molecular marker for predicting the prognosis of patients with astrocytoma and could be a novel target for treating astrocytoma.

Predictive value of the SLC22A18 protein expression in glioblastoma patients receiving temozolomide therapy

BackgroundOur previous study showed that SLC22A18 downregulation and promoter methylation were associated with the development and progression of glioma and the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In this study, we investigated the predictive value of SLC22A18 promoter methylation and protein expression in glioblastoma multiforme (GBM) patients receiving temozolomide (TMZ) therapy.Patients and methodsSLC22A18 promoter methylation and protein expression were examined by methylation-specific polymerase chain reaction (MSP) and Western blotting respectively, then we compared SLC22A18 promoter methylation and protein expression in tumor cell explants in regard to prediction of TMZ response and survival time of 86 GBM patients.ResultsSLC22A18 promoter methylation was detected in 61 of 86 (71%) samples, whereas 36 of 86 (42%) cases were scored positive for SLC22A18 protein expression. Overall SLC22A18 promoter methylation was significantly related to SLC22A18 protein expression, but a subgroup of cases did not follow this association. Multivariate Cox regression analysis indicated that SLC22A18 protein expression, but not promoter methylation, was significantly correlated with TMZ therapy. SLC22A18 protein expression predicted a significantly shorter overall survival in 51 patients receiving TMZ therapy, whereas no differences in overall survival were observed in 35 patients without TMZ therapy.ConclusionsThese results show that lack of SLC22A18 protein expression is superior to promoter methylation as a predictive tumor biomarker in GBM patients receiving temozolomide therapy.

Computational analysis identifies invasion-associated genes in pituitary adenomas

Pituitary adenomas are considered to be benign tumours. However, they can infiltrate surrounding tissues, which may cause a failure of complete removal during surgical resection. Thus far, no molecular biomarkers have been identified, which are able to reliably predict the behaviour of this type of tumour. In the present study, a list of differentially expressed genes in invasive pituitary adenomas was obtained using a computational bioinformatics analysis on the DNA microarray expression profiles. The gene expression datasets of a total of 16 samples were retrieved from the National Center for Biotechnology Information Gene Expression Omnibus database. The gene set enrichment analysis was later conducted on the significantly (FDR<0.05) differentially expressed genes. A total of 194 genes were identified as differentially expressed. The pathway impact analysis revealed that cell adhesion molecules may be vital in the progression of pituitary adenoma invasion. A total of six genes, claudin 7, contactin associated protein-like 2, integrin α6, junctional adhesion molecule 3, protein tyrosine phosphatase, receptor type C and cadherin-associated protein α1 were identified as molecular biomarkers for pituitary adenoma invasion. The present study identified six novel molecular biomarkers, which may be used for diagnostic or therapeutic purposes. However, further experimental investigations are required to validate the present findings.

Giant Serpentine Aneurysm of the Middle Cerebral Artery

BACKGROUND Giant serpentine aneurysms (GSAs) are a subgroup of giant intracranial aneurysms, distinct from saccular and fusiform varieties, that are defined as partially thrombosed giant aneurysms with tortuous internal vascular channel. Clinicopathologic characteristics of middle cerebral artery GSAs have been rarely reported in the literature, with discussion of radiologic characteristics only. We clarify patient clinical and neuroradiologic features and discuss the mechanism of formation and progression. CASE DESCRIPTION A 43-year-old woman presented with a GSA arising from the middle cerebral artery. There was a separate inflow and outflow channel of the aneurysm, with the outflow channel feeding the distal branches of the parent artery and supplying normal brain parenchyma. The GSA was treated successfully by aneurysmectomy and superficial temporal artery-middle cerebral artery bypass followed by proximal occlusion and vascular reconstruction. An aneurysm specimen was examined to correlate pathologic findings and morphologic characteristics. RESULT Pathologic results showed that thickness of the aneurysmal wall was typically increased and varied, and no internal elastic lamina or endothelial lining could be identified. The sac contained thrombi of various ages with recanalizing vessel formation and chronic inflammation infiltration. Intimal hyperplasia and neoangiogenesis in the wall and hyaline degeneration of the media were observed. Vessels coursing in their adventitia showed mucoid changes, which are responsible for the contrast enhancement of the aneurysmal rim on computed tomography scan. CONCLUSIONS GSAs are a specific pathologic entity with unique morphologic and pathologic characteristics that can affect intracranial blood vessels. The pathogenic mechanisms are unclear; this report suggests that GSAs may be associated with degeneration of the vascular wall.

The use of endoscopic-assisted burr-hole craniostomy for septated chronic subdural haematoma: A retrospective cohort comparison study

OBJECTIVE To complete a retrospective comparison of endoscope-assisted burr-hole craniostomy (EBHC) and ordinary burr-hole craniostomy (OBHC) in the treatment of septated chronic subdural hematoma (SCSH). METHODS A retrospective case note review comparing EBHC and OBHC of SCSH was therefore performed. Data of patients with a SCSH for EBHC or OBHC during the period from January 2011 to December 2016 were retrospectively collected and analysed. Of 73 patients, 42 underwent EBHC and 31 patients were treated by OBHC. The primary outcome measure was recurrence rate and secondary outcome measures were clinical outcome at first postoperative day, discharge and 6 months, the length of hospital stay for neurosurgery, the operative time, and the placement time of drainage tube. RESULT The rate of recurrence was significantly lower in the EBHC (0/42 0%) than in the OBHC (8/31, 25.8%) group (p = .0030). The rate of morbidity was significantly lower in the EBHC (2/42, 4.8%) than in the OBHC (11/31, 35.5%) group (p = .0121). At 30 days, mortality did not differ between groups. Significantly more patients treated with EBHC were alive at 6 months than were those with OBHC. No patient died as a consequence of the operative procedure in the both groups. A discharge GCS of 15 was recorded in more participants with EBHC than in those with OBHC. Gross neurological deficit was significantly less frequent in those with EBHC than in those with OBHC at first postoperative day and discharge, but did not differ at 6 month follow-up. The mean placement time of drainage tube was significantly less in those with EBHC (27.2 h) than in those with OBHC (52.0 h, p = .0055). The mean length of hospital stay for neurosurgery was 4 days in the EBHC group, while it was 5 days in the OBHC group (p = .0015). The mean hematoma reduction rate was significantly higher in those with EBHC than in those with OBHC at first postoperative day (85.3% vs 72.5%, p = .0037) and discharge (90.3% vs 85.1%, p = .0127). CONCLUSION Comparing two minimally invasive procedure protocols for treatment of SCSH, EBHC is a safe and effective surgical technique. It significantly surpasses the results obtained in OBHC in lowering recurrence rate, morbidity rate, placement time of drainage tube, and length of hospital stay for neurosurgery. We recommend EBHC technique to be widely used in the treatment of SCSH, even common chronic subdural hematoma (CSH), subacute and acute subdural hematomas, acute epidural hematomas and empyemas to avoid large craniotomies, particularly in elderly patients, so that patients can receive the best treatment on the basis of minimal trauma.

Clustering of self-organizing map identifies five distinct medulloblastoma subgroups

BACKGROUND Medulloblastoma is one the most malignant paediatric brain tumours. Molecular subgrouping these medulloblastomas will not only help identify specific cohorts for certain treatment but also improve confidence in prognostic prediction. OBJECTIVE Currently, there is a consensus of the existences of four distinct subtypes of medulloblastoma. We proposed a novel bioinformatics method, clustering of self-organizing map, to determine the subgroups and their molecular diversity. METHODS Microarray expression profiles of 46 medulloblastoma samples were analysed and five clusters with distinct demographics, clinical outcome and transcriptional profiles were identified. RESULTS The previously reported Wnt subgroup was identified as expected. Three other novel subgroups were proposed for later investigation. CONCLUSIONS Our findings underscore the value of SOM clustering for discovering the medulloblastoma subgroups. When the suggested subdivision has been confirmed in large cohorts, this method should serve as a part of routine classification of clinical samples.