Shangchen Xu

c-Met expression is associated with time to recurrence in patients with glioblastoma multiforme

The aim of this study was to explore the difference in c-Met expression between primary and recurrent glioblastoma multiforme (GBM), and to determine whether the dysregulation of c-Met expression has a role in the malignant progression of GBM. Paired primary and recurrent GBM specimens from the same patient were evaluated using immunohistochemical analysis. The association between c-Met expression and progression-free survival time (PFST) was analyzed. There was a significant difference in c-Met expression between primary and recurrent tumors (p=0.020), and patients with tumors expressing c-Met at a higher level had a significantly shorter PFST (6.1 months vs. 11.5 months; p=0.026). Our study indicates that recurrent GBM express c-Met at a higher level and that c-Met overexpression is associated with shorter PFST in patients with GBM. These findings suggest that c-Met potentially has an important role in the treatment of GBM.

Expression of high-mobility group AT-hook protein 2 and its prognostic significance in malignant gliomas

High-mobility group AT-hook protein 2 (HMGA2) is an architectural transcription factor associated with malignancy, invasiveness, and poor prognosis in a variety of human neoplasms. This study investigated HMGA2 expression and prognostic value in human gliomas. We also correlated HMGA2 expression with Ki-67 labeling index and matrix metalloproteinase-2. Expression of HMGA2 in 78 human gliomas and 7 human normal brain samples was studied using immunohistochemistry, and 29 gliomas were randomly selected and studied along with the normal brain by real-time quantitative polymerase chain reaction and Western blot analysis. Expression of HMGA2 protein was significantly higher in glioblastoma multiforme (World Health Organization [WHO] grade IV; P = .007) and anaplastic astrocytoma (WHO grade III; P = .037) than in diffuse astrocytoma (WHO grade II). Expression of HMGA2 correlated significantly with expression of Ki-67 (r = 0.415, P < .01) and matrix metalloproteinase-2 (r = 0.363, P < .01), but not with patient sex and age. The real-time quantitative polymerase chain reaction and Western blot analysis revealed similar results. Patients with tumors expressing HMGA2 at a higher level had a significantly shorter progression-free survival time (11.2 months versus 18.8 months; P = .021). Expression of HMGA2 significantly correlates with tumor cell proliferation, invasion, and survival in gliomas. The results suggest that HMGA2 has an important role in the treatment and prognosis of these cancers.

Polymorphism rs42524 of COL1A2 and sporadic intracranial aneurysms in the Chinese population

OBJECT The COL1A2 gene at 7q22.1 has been shown to be associated with familial intracranial aneurysms (IAs) in the Japanese population. In the present study, the authors investigated the correlation between the presence of the rs42524 polymorphism in COL1A2 and the occurrence of sporadic IAs in Chinese patients. METHODS The polymorphism rs42524 of the COL1A2 gene was identified by polymerase chain reaction-based restriction analysis in genomic DNA from 226 patients with sporadic IAs (mean age 51.49 +/- 11.47 years) and 326 control participants (mean age 52.33 +/- 10.50 years). Neurological assessments were performed using the Hunt and Hess grading system, and differences in allelic and genotypic frequencies between the patient and control groups were evaluated with the chi-square test. RESULTS There was a significant difference in either the genotype distribution (chi(2) = 11.99, p = 0.002) or allelic frequencies (chi(2) = 11.96, p = 0.001, odds ratio 2.579, 95% confidence interval 1.486-4.476) between patients with IAs and patients in the control group. CONCLUSIONS The rs42524 polymorphism of COL1A2 could be a genetic risk factor for sporadic IAs among individuals of Chinese Han ethnicity. This study is the first to confirm the association between COL1A2 and IAs.

Expression of hepatocyte growth factor and its receptor c-Met in human pituitary adenomas

Hepatocyte growth factor (HGF) and its receptor c-Met have been known as key determinants of growth and angiogenesis in some brain tumors like gliomas, meningiomas, and schwannomas. But little is known about their expression in pituitary adenomas. In this study, the expression of HGF and c-Met in pituitary adenomas of different histology types was investigated by immunohistochemistry, and correlative analysis of their expression with microvessel density (MVD), Ki-67 expression, and other clinicopathologic factors was made. The results showed that the expression of HGF and c-Met exists in 98% (64 of 65) and 92% (60 of 65) pituitary adenomas, respectively, and co-expression of them existed in 91% (59 of 65) adenomas. HGF had significant correlation with MVD (Spearmans correlation coefficient, r = .31, P = .01) and Ki-67 (r = .32, P = .01). c-Met had significant correlation with MVD (r = .30, P = .02) and Ki-67 (r = .38, P = .00). HGF and c-Met expression had no significant correlation with age or extrasellar extension. There were no significant differences in HGF and c-Met expression between pituitary adenomas of different histology types. The results indicate that HGF and c-Met are widely expressed in pituitary adenomas, and their expression correlates with MVD and Ki-67 expression.

The different HMGA1 expression of total population of glioblastoma cell line U251 and glioma stem cells isolated from U251

The high-mobility group A1 (HMGA1) protein is a non-histone architectural nuclear factor and participates in diverse biological processes, including gene transcription, embryogenesis, cell cycle regulation, apoptosis, and even neoplastic transformation. In our study, glioma stem cells (GSCs) expressing the surface marker CD133 from human glioblastoma cell line U251 were isolated using MACS column and were analyzed using immunofluorescence and flow cytometry (FCM). The different expression of HMGA1 was detected using real-time RT-PCR and Western blot at transcriptional and translational levels between U251 and isolated GSCs. The results show that GSCs were successfully isolated from U251 and cultured in serum-free medium (SMF). The percentage of GSCs in U251 was 0.32%±0.07%. HMGA1 expression was significantly higher in GSCs than in glioblastoma cells (P<0.05), up to 6.13±0.25-fold and 2.75±0.99-fold at transcriptional and translational levels, respectively. These results indicated HMGA1 is overexpressed in GSCs as compared to glioblastoma cell line U251, which points to the expression of HMGA1 being closely related to malignant proliferation, invasion, and differentiation of tumors from the prospective of tumor stem cells (TSCs). We conclude that HMGA1 may be a potential biomarker and rational therapeutic target for glioblastoma and GSC.

Asymmetry of cerebral blood flow measured with three-dimensional pseudocontinuous arterial spin-labeling mr imaging in temporal lobe epilepsy with and without mesial temporal sclerosis.

To investigate the asymmetry of quantitative cerebral blood flow (CBF) values in interictal temporal lobe epilepsy (TLE) patients with (TLE‐MTS) and without (TLE‐no) mesial temporal sclerosis.

High mobility group A1 expression shows negative correlation with recurrence time in patients with glioblastoma multiforme.

The aim of this study was to explore the difference in high mobility group A1 (HMGA1) expression and isocitrate dehydrogenase (IDH) 1 R132H point mutation in initial and recurrent glioblastoma multiforme (GBM), and to further identify whether the expression of HMGA1 has a role in the malignant progression of GBM. Paired initial and recurrent GBM specimens from the same patient were evaluated using immunohistochemical analysis. The association between HMGA1 expression and progression-free survival time (PFST) was analyzed. Three patients were confirmed with IDH-1 R132H mutations in both initial and recurrent groups (3/25, 12%). There was a significant difference in HMGA1 expression between initial and recurrent GBM (P=0.002), and patients with tumors expressing HMGA1 at higher level had a significantly shorter PFST (7.3 months versus 11.1months; P=0.044). Our study indicates that recurrent GBM express HMGA1 at a higher level and that HMGA1 overexpressoin is associated with shorter PFST in patients with GBM. These findings suggest that HMGA1 potentially plays an important role in the treatment of GBM.

Collision Tumor of Glioblastoma and Meningioma: Case Report and Literature Review

BACKGROUND Intracranial primary collision tumors of different histologic types are rare, and their occurrence is still unclear. CASE DESCRIPTION We describe a 66-year-old female who presented with headache, nausea, and vomiting. Magnetic resonance imaging scan showed that there were 2 primary intracranial tumors occurring simultaneously at adjacent sites of the right cerebral hemisphere. Tumor pathology showed 2 distinct tumors: meningioma (World Health Organization I) and glioblastoma. This is a rare case in which 2 different intracranial primary tumors occurred at adjacent sites, but the patient had no history of head trauma, neurologic surgery, or radiation therapy. CONCLUSIONS According to previous and present reports, the most common type of intracranial primary collision tumor is composed of a benign meningioma and a glioblastoma. During the occurrence of collision tumors, 1 tumor can play a role in the formation and growth of the other.

MRI-measured myocardial iron load in patients with severe diabetic heart failure

AIM To investigate whether a correlation exists between abnormal myocardial iron status and cardiac lipid deposition as well as other biomarkers in patients with diabetic heart failure (DHF). MATERIALS AND METHODS Seventeen volunteers (Group 1), 26 patients with non-severe DHF (Group 2), and 25 patients with severe DHF (Group 3) were recruited for this study. Myocardial middle-section T2* mapping and septal 1H magnetic resonance spectroscopy (1H-MRS) were performed using a 3 T magnetic resonance imaging (MRI) machine to assess the iron status and lipid deposition individually. Fasting venous blood was used to examine serum biomarkers. RESULTS Cardiac T2* (ms) of the three groups were 22.8±2.1, 21.7±1.8, and 18.6±1.3, respectively. The value of Group 3 was significantly lower than that of the other two groups (p<0.001). Myocardial triglyceride (%) levels differed among the three groups (Group 1, 0.53±0.13; Group 2, 1.11±0.29; Group 3, 1.47±0.12; p<0.001). Cardiac T2* was inversely correlated with both cardiac triglycerides and left ventricular ejection fraction (LVEF) in overall participants (Groups 1-3) or Group 3 (each p<0.001). CONCLUSIONS Abnormal myocardial iron status was found in patients with severe diabetic heart failure. Myocardial lipotoxicity may be responsible for this process.

Postcontrast T1 Mapping for Differential Diagnosis of Recurrence and Radionecrosis after Gamma Knife Radiosurgery for Brain Metastasis

BACKGROUND AND PURPOSE: The differential diagnosis of radionecrosis and tumor recurrence in brain metastases is challenging. We investigated the diagnostic efficiency of postcontrast T1 mapping in solving this problem. MATERIALS AND METHODS: Between March 2016 and June 2017, fifty-six patients with brain metastases who underwent contrast-enhanced cerebral T1 mapping were recruited for this prospective study. The findings revealed new enhancement after gamma knife radiosurgery. The subjects were assigned to radionecrosis and recurrence groups based on follow-up (median, 11.5 months) and histopathologic results. T1 values of lesions 5 (T15min) and 60 (T160min) minutes after administration of contrast agent and their difference (T1differ) were compared between the 2 groups with the 2-tailed Mann-Whitney U test. Receiver operating characteristic curves were used to determine the optimum cutoff values for differential diagnosis. RESULTS: There were significant differences between the 2 groups in T15min, T160min, and T1differ values (P = .012, P = .004, and P < .001, respectively). Relative to T15min and T160min, T1differ exhibited greater sensitivity and specificity (P < .001, respectively) in identifying radionecrosis. The optimum T1differ value for differential diagnosis was 71.1 ms (area under the curve = 0.97; 95% CI, 0.93–1.00), with sensitivity and specificity of 81.5% and 96.5%, respectively. CONCLUSIONS: Postcontrast T1 mapping is optimal for the differential diagnosis of radionecrosis and tumor recurrence. Among T1 parameters, T1differ is the most powerful parameter for differential diagnosis. Advantages in terms of quantitative analysis and high resolution portend the wide use of postcontrast T1 mapping in the future.