PCC0208017, a novel small-molecule inhibitor of MARK3/MARK4, suppresses glioma progression and

Gliomas are the most common primary intracranial neoplasms among all brain malignancies, and the microtubule affinity regulating kinases (MARKs) have become potential drug targets for glioma. Here, we report a novel dual small-molecule inhibitor of MARK3 and MARK4, designated as PCC0208017. PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4, and strongly reduced proliferation in three glioma cell lines. This compound attenuated glioma cell migration, glioma cell invasion, and angiogenesis. Molecular mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau, disrupted microtubule dynamics, and induced a G2/M phase cell cycle arrest. In an glioma model, PCC0208017 showed robust anti-tumor activity, blood-brain barrier permeability, and a good oral pharmacokinetic profile. Molecular docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and MARK4. Taken together, our study describes for the first time that PCC0208017, a novel MARK3/MARK4 inhibitor, might be a promising lead compound for treatment of glioma.

Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against prostate cancer cellsand

Tubulin has been shown to be an effective target for the development of cytotoxic agents against prostate cancer. Previously, we reported that Lx2-32c is an anti-tubulin agent with high binding affinity to tubulin. In this study, we investigated the potential of Lx2-32c to act as an effective cytotoxic agent in the treatment of prostate cancer. MTT assays showed that Lx2-32c was cytotoxic to all tested prostate cancer cell lines. The Lx2-32c-treated cells typically exhibited a rounded morphology associated with the onset of apoptosis, as evidenced by immunocytochemical staining. Human prostate cancer cell lines treated with Lx2-32c arrest in the G2/M phase of the cell cycle and the treatment is associated with an increased ratio of cells in the sub-G0/G1 phase as determined by flow cytometry. Furthermore, expression of the cleaved form of poly (ADP-ribose) polymerase in prostate cancer cell lines treated with Lx2-32c was shown by Western blotting assay. Xenograft implants of LNCaP and PC3-derived tumors in nude mice showed that Lx2-32c treatment significant inhibited tumor growth with effects equivalent to those of docetaxel. These findings demonstrate the potential of Lx2-32c as a candidate antitumor agent for the treatment of prostate cancer.

Radiosensitizing effect of 2-methoxyestradiol on NSCLC cell lines by blocking cell cycle / 中国病理生理杂志

AIM:To investigate the efficiency of 2-methoxyestradiol (2-ME) as radiosensitizing agent for the treatment of lung cancer cells. METHODS:Cell line A549 and GLC-82 originated from human non-small cell lung cancer were cultured in vitro. Study group (2-ME in different concentrations) and control group without 2-ME were set up. Cell proliferation was measured by MTT assay that lung cancer cells were treated with 2-ME for 24 h,then the cells were exposed from 0 to 8Gy radiation,and the survival fraction was determined by clone forming test. Flow cytometry was used to measure the effects of 2-ME on cell cycle distribution. RESULTS:MTT assay showed minimum effective concentration value was 0.15625×10~(-6) mol/L in GLC-82 and 1.25×10~(-6) mol/L in A549 cells. Compared to control group,exposed GLC-82 cells or A549 cells to minimum effective concentration of 2-ME for 24 h before irradiation resulted in an enhancement of radiation. The protection enhancement factor was 1.98 and 2.06 in GLC-82 and A549 cells,respectively. Flow cytometry analysis of cell cycle progression demonstrated G_2/M phase arrest in both cells in a dose dependent manner. No obvious change of CDK2 activity in both GLC-82 cells and A549 cells was observed. CONCLUSION:2-ME enhances radiosensitivity by G_2/M phase arrest in the cell cycle.

R-wave detection of ECG signal by using wavelet transform / 生物医学工程学杂志

The detection of R-wave of ECG is essential to the analysis of the heart rate variability (HRV). In this paper, an R-wave detection method using wavelet transform(WT) is presented in line with the principle of discrete wavelet transform(DWT) and multi-resolution technique (MRT). We made use of the special properties of dbl wavelet in time-domain, decomposed the original ECG signals into 3-level detailed signals on different frequency bands by using DWT with Mallat algorithm, and got appropriate threshold values in different high frequency bands to distinguish R-wave. It is concluded that the algorithm had significant effects on it, which is verified by MIT/BIH (Massachusetts Institute of Technology/Boston's Beth Israel Hospital) ECG Database. The results show that R-wave could be detected accurately and localized precisely by this method, even when the patient was seriously sick or the signal was disturbed by noise. Consequently the method has a quite high locating precision (its error is not more than two sampled points and about 85 percent of the points of R-wave in ECG signal are localized precisely) and the correct detection rate of R-wave is 99.8% by using wavelet transform, so this method is quite feasible.

Adhesion induces matrix metalloproteinase-9 gene expression in ovarian cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This work was conducted to investigate the expression of matrix metalloproteinase 9 (MMP 9) gene in cancer cells by fibronectin adhesion and the underlying mechanism of cell invasion.</p><p><b>METHODS</b>Following adhesion of ovarian cancer cells A2780 to fibronectin, mRNA expression of MMP cells were assayed by reverse transcription-polymerase chain reaction (RT-PCR). MMP9 promoter was cloned from genomic DNA of HT1080 cells with PCR. The MMP-9-pGL2 reporter gene vector was constructed and then transiently transfected into A2780 cells.</p><p><b>RESULTS</b>Adhesion induced the increase of cellular MMP9 mRNA content in A2780 cells, not affecting the expression of MMP2 or TIMP-1 gene. The stimulation was enhanced with the increase adhesion time. When the transfected cells were allowed to adhere and spread on FN-coated surface, the promoter activity of MMP9 gene was also enhanced dramatically.</p><p><b>CONCLUSION</b>Cell-ECM adhesion may stimulate the expression of MMP9 gene through stimulating the promoter activity, thereby enhancing cancer cell invasion and metastasis.</p>

The Control of Apoptosis and Drug Resistance in Ovarian Cancer Cells Which Overexpressed bcl-2 / 中国肿瘤生物治疗杂志

Objective: To investigate whether bcl-2 directly contributes to the development of drug resistance and apoptosis in o- varian cancer cell lines cells OC3. Methods: Retrovirus expression cector pLXSN-bcl-2 was constructed and was transfected to ovarian cancer cell line cells OC3 using Lipofectin,with empty vector pLXSN as a control. bcl-2 expession of transfected cells was analyzed by FACS and Western blot and Adr-induced cytotoxicity was measured by MTT assay. Apoptosis was also detected by PI DNA staining and DNA Ladder analysis.Results:pLXSN/bcl-2 transfected cells OC3/bcl-2 overexpressed bcl-2 and were resistant to Adr-induced cytotoxicity.The ability against Adr-induced apoptosis was increased. Conclusion: bcl-2 may play an important role in the resistance to Adr-inducing apoptosis, thereby increasing resistance of OC3/bcl-2 cells to chemotherapy.

EXTRACTION OF L-ARGININE FROM FERMENTATION BROTH BY ION-EXCHANGE PROCESS / 微生物学通报

The study showed that the L-argmine-adsorbing capacity of strong-acidic resin 001?7 was 1.135 meq per ml of wet resin by controlling the flow rate of the broth at 1/52 vvm, and the efficiency of the elution was higher by using ammnia water as an eluent at the flow rate of 1/50 vvm. About 160 ml of the above eluant was decolorized with 10 ml of 201?4 resin, the transparance of the decolorized eluant was over 90%, and no adsorption of L-arginine by the 201?4 resin was observed. Under the controlled conditions, the extraction yield of L-arginine reached over 95%.