Localization of CD26/DPPIV in nucleus and its nuclear translocation enhanced by anti-CD26 monoclonal antibody with anti-tumor effect

<p>Abstract</p> <p>Background</p> <p>CD26 is a type II, cell surface glycoprotein known as dipeptidyl peptidase (DPP) IV. Previous studies have revealed CD26 expression in T cell leukemia/lymphoma and malignant mesothelioma, and an inhibitory effect of anti-CD26 monoclonal antibody (mAb) against the growth of CD26+ cancer cells in vitro and in vivo. The function of CD26 in tumor development is unknown and the machinery with which the CD26 mAb induces its anti-tumor effect remains uncharacterized.</p> <p>Results</p> <p>The localization of CD26 in the nucleus of T cell leukemia/lymphoma cells and mesothelioma cells was shown by biochemical and immuno-electron microscopic analysis. The DPPIV enzyme activity was revealed in the nuclear fraction of T cell leukemia/lymphoma cells. These expressions of intra-nuclear CD26 were augmented by treatment with the CD26 mAb, 1F7, with anti-tumor effect against the CD26+ T cell leukemia/lymphoma cells. In contrast, the CD26 mAb, 5F8, without anti-tumor effect, did not augment CD26 expressions in the nucleus. Biotin-labeled, cell surface CD26 translocated into the nucleus constantly, and this translocation was enhanced with 1F7 treatment but not with 5F8.</p> <p>Conclusion</p> <p>These results indicate that the intra-nuclear CD26 which moves from plasma membrane may play certain roles in cell growth of human cancer cells.</p

Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer

A Phthalimide Derivative That Inhibits Centrosomal Clustering Is Effective on Multiple Myeloma

Despite the introduction of newly developed drugs such as lenalidomide and bortezomib, patients with multiple myeloma are still difficult to treat and have a poor prognosis. In order to find novel drugs that are effective for multiple myeloma, we tested the antitumor activity of 29 phthalimide derivatives against several multiple myeloma cell lines. Among these derivatives, 2-(2,6-diisopropylphenyl)-5-amino-1H-isoindole-1,3- dione (TC11) was found to be a potent inhibitor of tumor cell proliferation and an inducer of apoptosis via activation of caspase-3, 8 and 9. This compound also showed in vivo activity against multiple myeloma cell line KMS34 tumor xenografts in ICR/SCID mice. By means of mRNA display selection on a microfluidic chip, the target protein of TC11 was identified as nucleophosmin 1 (NPM). Binding of TC11 and NPM monomer was confirmed by surface plasmon resonance. Immunofluorescence and NPM knockdown studies in HeLa cells suggested that TC11 inhibits centrosomal clustering by inhibiting the centrosomal-regulatory function of NPM, thereby inducing multipolar mitotic cells, which undergo apoptosis. NPM may become a novel target for development of antitumor drugs active against multiple myeloma

Catalytic Synthesis of p-tert-Butylcatechol by Ionic Liquid

AbstractThe alkylation of catechol with methyltertiarybutyl ether (MTBE) catalyzed by acid-functionalized ionic liquid gives p-tert-butylcatechol was investigated. The results indicated that under optimized reaction condition of 393K; 2h; n(catachol): n(MTBE): n (IL) =1:3:0.02, the conversion of catechol and the selectivity of p-tert-butyl catechol (4-TBC) were 87.4% and 65.3% respectively

Bidirectional WDM Multi-Nodes Analog Radio-Over-Fiber Mobile Fronthaul Link Enhanced by Photonic Integrated Devices

A bidirectional wavelength division multiplexing (WDM) analog radio-over-fiber (A-RoF) mobile fronthaul (MFH) link is enhanced using photonic integrated devices. Two key photonic integrated devices are combined in the A-RoF link: an 8-channel InP directly modulated laser (DML) transmitter and a 32&#x00D7;100-GHz silicon array waveguide grating (AWG). The DML transmitter has 8 parallel monolithically integrated distributed feedback lasers, enabling cooperative and reconfigurable downlink analog transmission. Moreover, the 32&#x00D7;100-GHz AWG is featured by low insertion loss (&lt;4.5-dB) and low crosstalk (&lt;&#x2212;20.4-dB), to achieve a high-density WDM system. In the distributed field experiments, we have successfully demonstrated a bidirectional A-RoF MFH over 10-km standard single mode fiber, providing an 8&#x00D7;5-Gbit&#x002F;s 4-quadrature amplitude modulation (QAM) orthogonal frequency division modulation (OFDM) downlink transmission and a 3&#x00D7;12-Gbit&#x002F;s 16-QAM uplink transmission