The research on lapatinib in autophagy, cell cycle arrest and epithelial to mesenchymal transition via Wnt/ErK/PI3K-AKT signaling pathway in human cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) contributes to one of most common types of skin cancer. Epidermal growth factor receptor (EGFR) activation has been investigated to be associated with the development of cSCC. Lapatinib is an inhibitor targeting HER2/neu and EGFR pathway. We found that lapatinib can inhibit proliferation by enhancing apoptosis of human cSCC cell lines. The cSCC cell cycle distribution could be arrested in G2/M phase after lapatinib treatment. In the in vitro experiment, we found that lapatinib interrupted PI3K/AKT/mTOR signaling pathway in human cSCC cells. Furthermore, lapatinib could suppress epithelial to mesenchymal transition (EMT) via Wnt/ErK/PI3K-AKT signaling pathway to represent a promising anticancer drug for cSCC treatment.

[Clinical characteristics and LGI1 gene mutation analysis on an autosomal dominant lateral temporal lobe epilepsy].

OBJECTIVE: To report the clinical and genetic study of a new Chinese family with autosomal dominant lateral temporal lobe epilepsy (ADLTE). METHODS: The living affected members underwent a full clinical, neurophysiological, electroencephalogram (EEG), and magnetic resonance imaging (MRI) study. Genetic analysis was performed by LGI1 DNA sequence analysis. RESULTS: The clinical feature of the patients was coincidence wall with the definition of ADLTE by International League Against Epilepsy in 2001. The living affected members had an adult or children onset of drug-responsive tonic-clonic seizures or complex partial seizures constantly preceded by auditory or visionary aura. Routine EEG revealed no focal abnormalities over both temporal regions. MRI detected no structural abnormality. Analysis of LGI1 gene showed no mutation in all affected members. CONCLUSION: This kindred has typical clinical manifestations of ADLTE. The pathogenesis has no association with mutation of the exons of LGI1 gene.

Proteomic analysis of cerebrospinal fluid from patients with idiopathic temporal lobe epilepsy.

Proteomic analysis of cerebrospinal fluid (CSF) from patients with temporal lobe epilepsy (TLE) and controls was carried out using two-dimensional gel electrophoresis followed by liquid chromatography electrospray ionization tandem mass spectrometry. Five protein spots showed significant differential expression (p<0.05): vitamin D-binding protein (DBP) was elevated in the CSF of TLE patients whereas cathepsin D, apolipoprotein J, Fam3c, and superoxide dismutase 1 (SOD1) were decreased in the CSF of TLE patients. Additional six protein spots presented only in the CSF of epilepsy patients were identified as tetranectin (TN), talin-2, apolipoprotein E, immunoglobulin lambda light chain (IGL@), immunoglobulin kappa variable light chain 1-5 (IGKV1-5), and procollagen C-endopeptidase enhancer 1 (PCOLCE). Expression of DBP, SOD1 and talin-2 was validated by western blot. Our results may provide better understanding of the pathophysiologic mechanisms underlying epileptogenesis and possible epilepsy biomarkers.

Overexpression of N-WASP in the brain of human epilepsy.

Neuronal circuit remodeling is the most critical pathological characteristic closely associated with the initiation and maintenance of epilepsy; however, the exact mechanisms of neuronal remodeling need further elucidation. Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is a key regulator of the actin cytoskeleton that causes actin polymerization and thus neurite extension. Our previous research demonstrated that the upstream regulator of N-WASP, cell division cycle 42 GTP-binding protein (Cdc42), is significantly upregulated in the brains of patients with intractable epilepsy (IE). In addition, cDNA microarray analysis has shown that gene expression of N-WASP is notably enhanced in the epileptic brain, suggesting a possible role for N-WASP in epileptogenesis. Here, we investigated the expression of N-WASP and its downstream effector, actin-related protein 2/3 (Arp2/3), at the protein level in the temporal lobe of IE patient brains to explore its possible role in the genesis of IE. Forty surgical samples from brains of patients with IE and 20 control brain tissues were obtained for this study. The expression of N-WASP in the anterior temporal neocortex was detected using immunohistochemistry, immunofluorescence and western blotting; Arp2/3 expression was detected by western blotting. Compared with controls, N-WASP expression in brains of IE patients was significantly higher; similarly, Arp2/3 level was markedly increased in the IE patient group. These results suggest that increased expression of N-WASP in the human brain may be associated with human IE.

TDAG51 in the anterior temporal neocortex of patients with intractable epilepsy.

TDAG51 (T cell death-associated gene 51) is an apoptosis-associated protein. Our aim was to investigate TDAG51 expression in the anterior temporal neocortex of patients with intractable epilepsy (IE), and then to discuss the possible role of TDAG51 in IE. Tissue samples from the anterior temporal neocortex of 33 patients who had surgery for IE were used to detect TDAG51 expression by immunohistochemistry, immunofluorescence, and Western blotting. We compared these tissues with nine histologically normal anterior temporal lobes from intracranial hypertension patients who had decompression procedures. TDAG51 was mainly expressed in the cytoplasm of neurons and glial cells. TDAG51 in IE was significantly higher than that in the controls. These findings were consistently observed using Western blotting, immunofluorescence, and immunohistochemistry techniques. TDAG51 in patients with IE was significantly higher when compared with levels in the controls. This finding suggests TDAG51 is consistent with a possible role of this gene in the evolution of the pathology in IE.

HSPBAP1 is found extensively in the anterior temporal neocortex of patients with intractable epilepsy.

Heat Shock Protein BAP1 (heat shock 27-kDa-associated protein 1, HSPBAP1) inhibits the function of heat shock protein 27, which has a neuroprotective effect during experimentally induced epileptic neuropathology. In our study, fluorescence quantitative polymerase chain reaction, immunohistochemistry, immunofluorescence, western blot were used to test the levels of HSPBAP1 mRNA and protein in surgical samples of the anterior temporal neocortex of patients with intractable epilepsy (IE) and normal controls samples. HSPBAP1 mRNA was abnormally expressed in the anterior temporal neocortex of patients with IE. Moreover, HSPBAP1 was found extensively in the cytoplasm of neurons and glial cells in all epilepsy specimens. Western blot showed a clear immunoreactive band of HSPBAP1 in IE specimens whereas it was absent in control specimens. The expression of HSPBAP1 mRNA and protein in the anterior temporal neocortex from patients with IE may play a role in the development of epileptic seizures in patients with cell loss in this brain region. Additional studies will be required to elucidate the mechanism by which HSPBAP1 affects brain function in IE.

[Clinical and epidemiological features of the five kinds of new epileptic syndrome].

OBJECTIVE: To investigate the clinical and epidemiological feature of the five kinds of new epilectically syndrome. METHOD: A retrospective study was conducted, by computer inquiry and manual retrieval, on 5300 patients with complete history records who had been followed up regularly in the epilepsy center of the First Affiliated Hospital of Chongqing University in the past 20 years to discover the cases that could be diagnosed as with the five kinds of new epileptic syndromes. RESULTS: Survey was finished in 4894 of the 5300 patients. Two cases of familial temporal lobe epilepsy, one case of familial partial epilepsy with variable foci, fourteen cases with mesial temporal epilepsy, and five cases with startle-provoked epileptic were discovered. CONCLUSION: Patients with the five kinds of new epileptic syndrome have been discovered in China too. It is beneficial to study the clinical and epidemiological features of those new epileptic syndromes.