Clinical Value of Machine Learning in the Automated Detection of Focal Cortical Dysplasia Using Quantitative Multimodal Surface-Based Features.

Objective: To automatically detect focal cortical dysplasia (FCD) lesion by combining quantitative multimodal surface-based features with machine learning and to assess its clinical value. Methods: Neuroimaging data and clinical information for 74 participants (40 with histologically proven FCD type II) was retrospectively included. The morphology, intensity and function-based features characterizing FCD lesions were calculated vertex-wise on each cortical surface and fed to an artificial neural network. The classifier performance was quantitatively and qualitatively assessed by performing statistical analysis and conventional visual analysis. Results: The accuracy, sensitivity, specificity of the neural network classifier based on multimodal surface-based features were 70.5%, 70.0%, and 69.9%, respectively, which outperformed the unimodal classifier. There was no significant difference in the detection rate of FCD subtypes (Pearson's Chi-Square = 0.001, p = 0.970). Cohen's kappa score between automated detection outcomes and post-surgical resection region was 0.385 (considered as fair). Conclusion: Automated machine learning with multimodal surface features can provide objective and intelligent detection of FCD lesion in pre-surgical evaluation and can assist the surgical strategy. Furthermore, the optimal parameters, appropriate surface features and efficient algorithm are worth exploring.

[Effect of IL-24 gene expression on the growth of glioma cells in vitro and in vivo].

OBJECTIVE: To investigate the effect of IL-24 expression on the growth of glioma cells. METHODS: The IL-24 gene was transfected into rat glioma C6 cells with a retroviral vector. The expression of IL-24 in C6/IL-24 glioma cells was confirmed by RT-PCR. MTT assay and flow cytometry were used to study tumor cell proliferation in vitro. Tumorigenicity in vivo was studied in inbred SD male rats by the growth of intracerebrally inoculated tumor. RESULTS: It was confirmed by RT-PCR that the exogenous IL-24 gene expressed in C6/IL-24 cell. The C6/IL-24 cell proliferation in vitro and tumorigenicity in vivo were both inhibited compared with its parental C6 cell. CONCLUSION: IL-24 expression in glioma cells somehow inhibits their growth in vitro and in vivo.

Tetramethylpyrazine induces SH-SY5Y cell differentiation toward the neuronal phenotype through activation of the PI3K/Akt/Sp1/TopoIIß pathway.

Tetramethylpyrazine (TMP) is an active compound extracted from the traditional Chinese medicinal herb Chuanxiong. Previously, we have shown that TMP induces human SH-SY5Y neuroblastoma cell differentiation toward the neuronal phenotype by targeting topoisomeraseIIß (TopoIIß), a protein implicated in neural development. In the present study, we aimed to elucidate whether the transcriptional factors specificity protein 1 (Sp1) and nuclear factor Y (NF-Y), in addition to the upstream signaling pathways ERK1/2 and PI3K/Akt, are involved in modulating TopoIIß expression in the neuronal differentiation process. We demonstrated that SH-SY5Y cells treated with TMP (80µM) terminally differentiated into neurons, characterized by increased neuronal markers, tubulin ßIII and microtubule associated protein 2 (MAP2), and increased neurite outgrowth, with no negative effect on cell survival. TMP also increased the expression of TopoIIß, which was accompanied by increased expression of Sp1 in the differentiated neuron-like cells, whereas NF-Y protein levels remained unchanged following the differentiation progression. We also found that the phosphorylation level of Akt, but not ERK1/2, was significantly increased as a result of TMP stimulation. Furthermore, as established by chromatin immunoprecipitation (ChIP) assay, activation of the PI3K/Akt pathway increased Sp1 binding to the promoter of the TopoIIß gene. Blockage of PI3K/Akt was shown to lead to subsequent inhibition of TopoIIß expression and neuronal differentiation. Collectively, the results indicate that the PI3K/Akt/Sp1/TopoIIß signaling pathway is necessary for TMP-induced neuronal differentiation. Our findings offer mechanistic insights into understanding the upstream regulation of TopoIIß in neuronal differentiation, and suggest potential applications of TMP both in neuroscience research and clinical practice to treat relevant diseases of the nervous system.

Mechanism of multidrug resistance of human small cell lung cancer cell line H446/VP.

BACKGROUND: Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. This study aimed to investigate the mechanism of human small cell lung cancer cell line resistance to etoposide (VP-16), H446/VP. METHODS: The cell viability was measured by MTT assay. Immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting methods were used to detect the multidrug resistance gene (MDR1), bcl-2, bax and the topoisomerase II (Topo II) expressions in H446 and H446/VP cells after treated with or without VP-16. RESULTS: The 50% inhibition concentration (IC50) of VP-16 on H446 cells was 49 mg/L, and 836 mg/L was for H446/VP cells. The expressions of MDR1 and bcl-2 were up-regulated, while the amounts of bax and Topo II were reduced in H446/VP cells. After treated with 49 mg/L of VP-16, it showed that the drug could significantly inhibit bcl-2 and Topo II expressions, and increase bax expression in H446 cells compared with that of H446/VP cells. CONCLUSIONS: The H446/VP cell was stably resistant to VP-16. The decreased expression of Topo II was correlated with the H446/VP multidrug resistance. The elevated expressions of MDR1, and the altered apoptotic pathways also played an important role in VP-16 induced multidrug resistance of SCLC.

[Retrovirus-mediated IL-18 gene expression in rat C6 glioma cell line].

AIM: To set up rat C6 glioma cell line C6/IL-18 expressing IL-18 gene and explore the effect of IL-18 on the growth of C6 cells. METHODS: The IL-18 gene was transferred into the C6 cells by a retrovirus vector. After screening with G418, the C6/IL-18 cells were obtained. IL-18 mRNA expression in C6/IL-18 cells was detected with RT-PCR. The expression of IL-18 protein was detected by flow cytometry and immunocytochemical staining. In order to analyze the activity of the expressed IL-18 protein, ELISA was used to detect the ability to secrete IFN-gamma by rat splenocytes induced with the culture supernatant of C6/IL-18 cells. The in-vitro proliferation of C6/IL-18 cells was detected by MTT colorimetry and flow cytometry. The rat model was used to observe the tumorigenic activity of the C6/IL-18 cells. RESULTS: IL-18 mRNA and protein were stably expressed in C6/IL-18 cells. The culture supernatant of C6/IL-18 cells induced secretion of IFN-gamma by rat splenocytes. At the same time, the proliferation rate and in-vivo tumorigenicity of C6/IL-18 cells were markedly reduced as compared with parental C6 cells. CONCLUSION: Exogenous IL-18 gene can inhibit the proliferation and in-vivo tumorigenicity of C6 cells.