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  • Article
    Li W, Qian L, Lin J, Huang G, Hao N, Wei X, Wang W, Liang J.
    Oncotarget. 2017 Sep 12;8(39):65143-65151.
    Our recent studies have shown that CD44, a cell-surface protein with functions in many biologic processes, involved in glucose metabolism of prostate cancer cells. However, the molecular mechanisms of the regulation need to be further elucidated. In present study, LNCaP cells infected with lentivirus vector overexpressing CD44. The expression levels of key enzymes in glucose metabolism known as PDK1 and PFKFB4 were determined using QRT-PCR and western blot. PDK1 and PFKFB4 in LNCaP and PC3 cells were knocked down with shRNA respectively, and then cell proliferation, invasion and cell migration assay were performed. We found that overexpression of CD44 increased expression levels of PDK1 and PFKFB4 in LNCaP cells. Silencing of PDK1 and PFKFB4 could decrease cell proliferation, inhibit invasion and migration ability of prostate cancer cells. In addition, CD44 inhibitor could decrease glucose consumption and increase ROS levels of PC-3 cells significantly, as well as sensitize PC-3 cells to docetaxel. Taken together, CD44 could modulate aggressive phenotype of prostate cancer cells, by regulation of the expression of PDK1 and PFKFB4. CD44 may be a novel potential therapeutic target.
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  • Article
    Brouwer MC, Baas F, van der Ende A, van de Beek D.
    PLoS One. 2013;8(5):e65151.
    It has been suggested that genetic variants in mannose binding lectin (MBL2) influence susceptibility and outcome of invasive pneumococcal disease. We assessed the influence of genetic variation in MBL2 on susceptibility, outcome and causative serotype of pneumococcal meningitis in a prospective nationwide cohort study including 299 white patients and 216 controls. We assessed functionality of the genetic polymorphisms by measuring levels of MBL, C3a, iC3b, C5a and sC5b-9 in cerebrospinal fluid. We also performed a meta-analysis of studies on MBL2 polymorphisms and susceptibility to invasive pneumococcal disease. The risk of contracting pneumococcal meningitis was substantially increased for white individuals homozygous with the defective MBL2 0/0 genotype (odds ratio [OR] 8.21, 95% confidence interval [CI] 1.05-64.1; p = 0.017). CSF MBL levels were significantly lower in patients with the A/0 and 0/0 genotype compared to homozygotes for the wild-type alleles (A/A; p<0.001). CSF MBL levels were positively correlated with C3a and iC3b levels, indicating complement activation by the lectin pathway. The effect of MBL2 genetic variants on susceptibility remained robust in a meta-analysis including 5 studies with 287 patients (OR 2.33, 99% CI 1.39-3.90). We conclude that MBL2 polymorphisms influence CSF MBL levels and substantially increase the risk of pneumococcal meningitis.
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  • Article
    Hesterman JY, Kupinski MA, Clarkson E, Wilson DW, Barrett HH.
    Proc SPIE Int Soc Opt Eng. 2007 Jan 01;6515(65151G):1-10.
    Evaluation of imaging hardware represents a vital component of system design. In small-animal SPECT imaging, this evaluation has become increasingly difficult with the emergence of multi-pinhole apertures and adaptive, or patient-specific, imaging. This paper will describe two methods for hardware evaluation using reconstructed images. The first method is a rapid technique incorporating a system-specific non-linear, three-dimensional point response. This point response is easily computed and offers qualitative insight into an aperture's resolution and artifact characteristics. The second method is an objective assessment of signal detection in lumpy backgrounds using the channelized Hotelling observer (CHO) with 3D Laguerre-Gauss and difference-of-Gaussian channels to calculate area under the receiver-operating characteristic curve (AUC). Previous work presented at this meeting described a unique, small-animal SPECT system (M(3)R) capable of operating under a myriad of hardware configurations and ideally suited for image quality studies. Measured system matrices were collected for several hardware configurations of M(3)R. The data used to implement these two methods was then generated by taking simulated objects through the measured system matrices. The results of these two methods comprise a combination of qualitative and quantitative analysis that is well-suited for hardware assessment.
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