Yang H.,Guangzhou University |
Cai L.,Guangdong 999 Brain Hospital |
Zhang Y.,Guangzhou University |
Tan H.,First Affiliated Hospital |
And 3 more authors.
Journal of Molecular Diagnostics | Year: 2014
Epidermal growth factor receptor (EGFR) mutations in cerebrospinal fluid (CSF) might be useful predictive markers for EGFR tyrosine kinase inhibitor treatment of intracranial metastatic tumors. In this retrospective study, amplification refractory mutation system (ARMS)-PCR assays were used to investigate the EGFR gene status in 30 lung adenocarcinoma patients with brain metastases. A total of 16 patients tested positive for EGFR-activating mutations in CSF or tumor tissues. These included L858R mutation in exon 21 in six CSF samples and exon 19 deletions in seven CSF samples. EGFR mutations were detected between CSF and primary tumor samples with a 75% positive predictive value (95% CI, 0.45-1.00), 75% negative predictive value (95% CI, 0.51-0.99), 67% sensitivity (95% CI, 0.36-0.97), and 82% specificity (95% CI, 0.59-1.00). Most of the patients who had EGFR mutations in CSF achieved good responses with EGFR-tyrosine kinase inhibitor treatment. In conclusion, ARMS-PCR could be a sensitive method of detecting EGFR mutations in the CSF of patients with lung adenocarcinoma with brain metastases. As such, ARMS-PCR could play an important role in guiding EGFR-tyrosine kinase inhibitor treatments of intracranial tumors and for diagnosing brain metastases in patients with lung adenocarcinoma. © 2014 American Society for Investigative Pathology.
News Article | November 17, 2016
Glioblastoma multiforme remains the most common and highly lethal brain cancer and is known for its ability to relapse. Researchers at The University of Texas MD Anderson Cancer Center have identified a pathway by which cancer cells aggressively spread and grow in the brain, opening up new possibilities for treatment. Study findings were published in the Nov. 17 online version of Cell. Co-authors included Baoli Hu, Ph.D., senior research scientist, Y. Alan Wang, Ph.D., associate professor, and Ronald A. DePinho, M.D., professor, all of Cancer Biology, and Qianghu Wang Ph.D., Bioinformatics and Computational Biology. "The poor prognosis of glioblastoma relates to the near universal recurrence of tumors despite robust treatment including surgery, radiotherapy and chemotherapy," said Hu. "Our study shows the potential for a new therapeutic strategy based on targeting the mechanisms allowing glioma to re-grow aggressively in the brain." Hu and his colleagues developed a glioblastoma model to locate glioma stem cells, which, like all stem calls, have the ability to become other cell types. The researchers further found that the gene, WNT5A, when activated, allowed glioma stem cells to transition, leading to invasive tumor growth. "We uncovered a process by which glioma stem cells mediated by the WNT5A gene become endothelial-like cells," said Hu. "These new cells known as GdECs, recruit existing endothelial cells to form a niche supporting the growth of invasive glioma cells away from the primary tumor, and often leading to satellite "lesions" and disease recurrence." Clinical data revealed higher WNT5A and GdECs expression in these satellite lesions and recurrent tumors than was observed in the primary tumors, affirming the tie between WNT5A-mediated stem cell differentiation and glioma cell spread throughout the brain, and contributing to the cancer's lethalness. The study established WNT5A as a key factor in glioma stem cells transitioning to GdECs. The team believes this opens up the possibility for a new therapeutic strategy for patients with glioblastoma. Recent clinical data show the FDA-approved drug, bevacizumab, did not benefit patients as a first line treatment of recurrent glioblastoma by targeting vascular endothelial growth factors (VEGF). With this new information, the study team proposes an additional therapeutic approach targeting WNT5A and VEGF signaling pathways for recurrent glioblastoma. "Our preliminary data show that bevacizumab may increase WNT5A-mediated GdECs differentiation and recruitment of existing endothelial cells resulting in no proven benefit to patients with glioblastoma" said Hu. "This new strategy should improve the outcome of brain cancer patients undergoing VEGF therapy, by limiting new tumor growth and invasion, and disease recurrence," said Hu. MD Anderson study team members included Y. Alan Wang, Ph.D., Sujun Hua, Ph.D., Charles-Etienne Sauvé, Derrick Ong, Ph.D., Zheng Lan, Ph.D., Yan Wing Ho, Ph.D., Marta Monasterio, Ph.D., Xin Lu, Ph.D., Pingna Deng, Guocan Wang, Ph.D., Wen-Ting Liao, Ph.D., Denise Spring, Ph.D., Jian Hu, Ph.D., and Ronald DePinho, M.D., all of Cancer Biology; Roeland Verhaak, Ph.D., Bioinformatics and Computational Biology; Jianhua Zhang, Ph.D., and Lynda Chin, M.D., Genomic Medicine; Yi Zong, Ph.D., Epigenetics and Molecular Carcinogenesis; Zhi Tan, Experimental Therapeutics; Lynda Corley and Gregory Fuller, M.D., Ph.D., Pathology; and Erik Sulman, M.D., Ph.D., Radiation Oncology. Other participating institutions included Dana-Farber Cancer Institute, Boston; Nanjing Medical University, Nanjing, China; Guangdong 999 Brain Hospital, Guangzhou, China; the Fondazione IRCCS Istituto Neurologico C. Besta, Milan; and the University of California, San Francisco. The study was funded by National Institutes of Health (P50 CA097257, 2P50CA127001, 5P01CA095616, and P30CA16672).
Wang Y.-G.,Xijing University |
Li Z.,Weifang Peoples Hospital |
Zhang W.,Guangdong 999 Brain Hospital |
Prakash R.,Ms Ramaiah Medical College
Epilepsy and Behavior | Year: 2014
Background: It is well known that dissociative experiences coexist with various epilepsy syndromes. However, the prevalence of dissociative experiences in different subtypes of epilepsy remains unknown. This is especially important because of the current prevalent view that the etiology of dissociation in seizures is neurobiological rather than psychosocial. The amygdala especially has been implicated in such dissociative features of epilepsy. This would indirectly imply that the patients with CPS have higher prevalence of dissociative symptoms compared with those with GTCS. Methodology: We studied and compared the dissociative experiences as well as the depression and anxiety levels between 24 patients suffering from temporal lobe epilepsy and 26 patients suffering from generalized tonic-clonic seizures. We used the Dissociative Experiences Scale to evaluate the dissociative experiences. A third group of healthy individuals was included as the control group. The statistical significance was fixed at 0.05. Results: There were significant differences between the scores of DES-II of the healthy individuals and those of patients with epilepsy. However, there were no significant differences between the DES scores of different patients with epilepsy categorized according to neuropathology. There were also no significant differences between HAM-A and HAM-D scores between groups with epilepsy, but the scores were higher than those of the healthy individuals. There were significant differences between the DES scores in different sociodemographic groups such that higher scores were observed in groups with lower education (p. <. 0.05). In addition, the scores on DES were higher in individuals with low socioeconomic status than in those with high socioeconomic status. Conclusion: The patients with temporal lobe epilepsy and those with generalized tonic-clonic seizures have similar dissociative experiences which are both more than those found in individuals without epilepsy. However, these dissociative experiences may not be related to the neuropathological parameters as much as they are to the sociodemographic parameters like education, age, socioeconomic status, and sex. This shows that the psychopathology of dissociation in epilepsy is similar to that of the general population. © 2014.
Huang S.,South China Normal University |
Li Y.,South China Normal University |
Zhang W.,Guangdong 999 Brain Hospital |
Zhang B.,Guangzhou University |
And 4 more authors.
Journal of Neuroscience | Year: 2015
Multisensory information competes for preferential access to consciousness. It remains unknown what neural processes cause one particular modality to win multisensory competition and eventually dominate behavior. Thus, in a paradigm in which human participants sought to make simultaneous auditory and visual detection responses, we sought to identify prestimulus and poststimulus neural signals that were associated with auditory and visual dominance on each trial. Behaviorally, visual detection responses preceded auditory responses more frequently than vice versa. Even when visual responses were preceded by auditory responses, they recovered more quickly from previous responses, indicating the dominance of vision over audition. Neurally, visual precedence was associated with increased prestimulus activity in the prefrontal cortex and reduced prestimulus activity in the default-mode network, and increased poststimulus connectivity between the prefrontal cortex and the visual system. Moreover, the dorsal visual stream showed not only increased activity in post-perceptual phases but also enhanced connectivity with the sensorimotor cortex, indicating the functional role of the dorsal visual stream in prioritizing the flow of visual information into the motor system. In contrast, auditory precedence was associated with increased prestimulus activity in the auditory cortex and increased poststimulus neural coupling between the auditory and the sensorimotor cortex. Finally, whenever one modality lost multisensory competition, the corresponding sensory cortex showed enhanced connectivity with the default-mode network. Overall, the outcome of audiovisual competition depended on dynamic interactions between sensory systems and both the fronto-sensorimotor and the default-mode network. Together, these results revealed both the neural causes and the neural consequences of visual and auditory dominance during multisensory competition. © 2015 the authors.
Qu S.-S.,Southern Medical University |
Huang Y.,Southern Medical University |
Zhang Z.-J.,Chinese University of Hong Kong |
Chen J.-Q.,Southern Medical University |
And 8 more authors.
Journal of Psychiatric Research | Year: 2013
Acupuncture possesses the antidepressant potential. In this 6-week randomized controlled trial with 4-week follow-up, 160 patients with major depressive disorder (MDD) were randomly assigned to paroxetine (PRX) alone (. n = 48) or combined with 18 sessions of manual acupuncture (MA, n = 54) or electrical acupuncture (EA, n = 58). Treatment outcomes were measured mainly using the 17-item Hamilton Depression Rating Scale (HAMD-17), Self-rating Depression Scale (SDS), clinical response and remission rates. Average PRX dose taken and proportion of patients who required an increased PRX dose due to symptom aggravation were also obtained. Both additional MA and EA produced a significantly greater reduction from baseline in score on HAMD-17 and SDS at most measure points from week 1 through week 6 compared to PRX alone. The clinical response was markedly greater in MA (69.8%) and EA (69.6%) groups than the group treated with PRX alone (41.7%, P = 0.004). The proportion of patients who required an increase dose of PRX due to symptom aggravation was significantly lower with MA (5.7%) and EA (8.9%) than PRX alone (22.9%, P = 0.019). At 4 weeks follow-up after completion of acupuncture treatment, patients with EA, but not MA, continued to show significantly greater clinical improvement. Incidence of adverse events was not different in the three groups. Our study indicates that acupuncture can accelerate the clinical response to selective serotonin reuptake inhibitors (SSRIs) and prevent the aggravation of depression. Electrical acupuncture may have a long-lasting enhancement of the antidepressant effects (Trial Registration: ChiCTR-TRC-08000278). © 2013 Elsevier Ltd.
An J.,Southern Medical University |
Fang P.,National University of Defense Technology |
Wang W.,Guangdong 999 Brain Hospital |
Liu Z.,Southern Medical University |
And 2 more authors.
NeuroReport | Year: 2014
Statistical analysis on diffusion tensor imaging has been used extensively in mesial temporal lobe epilepsy (mTLE) and most studies report decrease in fractional anisotropy (FA) in multiple white matter regions. However, these findings vary across studies and between regions. Therefore, in this study, we used tract-based spatial statistics along with machine learning approaches to investigate the whole-brain white matter changes between 17 left mTLE patients and 15 right mTLE patients and 34 matched healthy controls. The results showed that the three groups could be distinguished from each other with promising accuracy. Compared with controls, the FA value of the most discriminating voxels was decreased in the ipsilateral limbic system, corpus callosum, and temporal white matter in both patient groups. Compared with right mTLE, left mTLE had decreased FA in the left temporal white matter, whereas right mTLE had decreased FA in the right frontal and temporal white matter, and right posterior corona radiata. These findings not only provide useful information for lateralization of the seizure focus but can also be used as a potential biomarker for the diagnosis and treatment of the mTLE. This may be helpful in assessment of patients with mTLE when no lesion is detected on visual evaluation. © Lippincott Williams & Wilkins.
Wang J.,South China Normal University |
Qiu S.,Southern Medical University |
Xu Y.,South China Normal University |
Liu Z.,Southern Medical University |
And 6 more authors.
Clinical Neurophysiology | Year: 2014
Objective: Temporal lobe epilepsy (TLE) is one of the most common forms of drug-resistant epilepsy. Previous studies have indicated that the TLE-related impairments existed in extensive local functional networks. However, little is known about the alterations in the topological properties of whole brain functional networks. Method: In this study, we acquired resting-state BOLD-fMRI (rsfMRI) data from 26 TLE patients and 25 healthy controls, constructed their whole brain functional networks, compared the differences in topological parameters between the TLE patients and the controls, and analyzed the correlation between the altered topological properties and the epilepsy duration. Results: The TLE patients showed significant increases in clustering coefficient and characteristic path length, but significant decrease in global efficiency compared to the controls. We also found altered nodal parameters in several regions in the TLE patients, such as the bilateral angular gyri, left middle temporal gyrus, right hippocampus, triangular part of left inferior frontal gyrus, left inferior parietal but supramarginal and angular gyri, and left parahippocampus gyrus. Further correlation analysis showed that the local efficiency of the TLE patients correlated positively with the epilepsy duration. Conclusion: Our results indicated the disrupted topological properties of whole brain functional networks in TLE patients. Significance: Our findings indicated the TLE-related impairments in the whole brain functional networks, which may help us to understand the clinical symptoms of TLE patients and offer a clue for the diagnosis and treatment of the TLE patients. © 2014 International Federation of Clinical Neurophysiology.
Wang Y.,Jinan University |
Jia Y.,Jinan University |
Chen X.,Guangdong 999 Brain Hospital |
Ling X.,Jinan University |
And 3 more authors.
Journal of Psychopharmacology | Year: 2012
An excess of glucocorticoids has been associated with hippocampal pathology in major depressive disorder (MDD). However, the relationships between depression, hippocampal structure and function, and cortisol levels are unclear, and the effects of antidepressant treatment on the measures are not well studied. For this study, 26 first-episode, treatment-naive, non-late-life adult depressed patients and 13 healthy controls were enrolled. Subjects underwent proton magnetic resonance spectroscopy (1H MRS) to obtain metabolite levels from the bilateral hippocampus. Patients with MDD were treated with serotonergic-noradrenergic reuptake inhibitor duloxetine for 12 weeks. After the 12-week period, all subjects with MDD underwent 1H MRS again. Morning serum cortisol levels also were measured both before and after antidepressant treatment. Comparison of baseline values indicated that there were no significant differences in any of the metabolite ratios (N-acetyl aspartate/creatine (NAA/Cr) and choline (Cho)/Cr) in the bilateral hippocampus. After treatment, NAA/Cr ratios increased significantly in the right hippocampus compared with pre-treatment values. There was no correlation between morning serum cortisol levels and bilateral hippocampal NAA/Cr or Cho/Cr in patients with MDD. These findings suggest that there are unaltered hippocampal metabolites in the early stage of MDD. Antidepressant treatment may affect hippocampal NAA levels in patients with MDD. In addition, the results do not support cortisol-mediated hippocampal neurotoxicity as the major etiological mechanism. © The Author(s) 2012.
Wang Y.,Jinan University |
Feng Y.,Guangdong 999 Brain Hospital |
Jia Y.,Jinan University |
Wang W.,Guangdong 999 Brain Hospital |
And 5 more authors.
Journal of Affective Disorders | Year: 2014
Objectives Auditory sensory gating deficits have been reported in subjects with bipolar disorder, but the hemispheric and neuronal origins of this deficit are not well understood. Moreover, gating of the auditory evoked components reflecting early attentive stage of information processing has not been investigated in bipolar disorder. The objectives of this study were to investigate the right and left hemispheric auditory sensory gating of the M50 (preattentive processing) and M100 (early attentive processing) in patients diagnosed with bipolar I disorder by utilizing magnetoencephalography (MEG). Methods Whole-head MEG data were acquired during the standard paired-click paradigm in 20 bipolar I disorder patients and 20 healthy controls. The M50 and the M100 responses were investigated, and dipole source localizations were also investigated. Sensory gating were determined by measuring the strength of the M50 and the M100 response to the second click divided by that of the first click (S2/S1). Results In every subject, M50 and M100 dipolar sources localized to the left and right posterior portion of superior temporal gyrus (STG). Bipolar I disorder patients showed bilateral gating deficits in M50 and M100. The bilateral M50 S2 source strengths were significantly higher in the bipolar I disorder group compared to the control group. Limitations The sample size was relatively small. More studies with larger sample sizes are warranted. Bipolar subjects were taking a wide range of medications that could not be readily controlled for. Conclusions These findings suggest that bipolar I disorder patients have auditory gating deficits at both pre-attentive and early attentive levels, which might be related to STG structural abnormality. © 2013 The Authors.
Li X.,Guangdong 999 Brain Hospital |
Wang Y.,Guangdong 999 Brain Hospital
Neurological Sciences | Year: 2014
Here, we present a rare case of a lateral medullary infarction with ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy. In this case, we proved Opalski's hypothesis by diffusion tensor tractography that ipsilateral hemiparesis in a medullary infarction is due to the involvement of the decussated corticospinal tract. We found that the clinical triad of ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy, which had been regarded as a variant of medial medullary syndrome, turned out to be caused by lateral lower medullary infarction. Therefore, this clinical triad does not imply the involvement of the anteromedial part of medulla oblongata, when it is hard to distinguish a massive lateral medullary infarction from a hemimedullary infarction merely from MR images. At last, we suggest that hyperreflexia and Babinski's sign may not be indispensable to the diagnosis of Opalski's syndrome and we propose that "hemimedullary infarction with ipsilateral hemiparesis" is intrinsically a variant of lateral medullary infarction. © 2014 Springer-Verlag.