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Articles by L Ma
Total Records ( 7 ) for L Ma
  J Xiao , S Yin , Y Li , S Xie , D Nie , L Ma , X Wang , Y Wu and J. Feng
 

S-phase kinase-associated protein 2 (SKP2) gene is a tumor suppressor gene, and is involved in the ubiquitin-mediated degradation of P27kip1. SKP2 and P27kip1 affect the proceeding and prognosis of leukemia through regulating the proliferation, apoptosis and differentiation of leukemia cells. In this study, we explored the mechanism of reversing of HL-60/A drug resistance through SKP2 down-regulation. HL-60/A cells were nucleofected by Amaxa Nucleofector System with SKP2 siRNA. The gene and protein expression levels of Skp2, P27kip1, and multi-drug resistance associated protein (MRP) were determined by reverse transcription-polymerase chain reaction and western blot analysis, respectively. The cell cycle was analyzed by flow cytometry. The 50% inhibitory concentration value was calculated using cytotoxic analysis according to the death rate of these two kinds of cells under different concentrations of chemotherapeutics to compare the sensitivity of the cells. HL-60/A cells showed multi-drug resistance phenotype characteristic by cross-resistance to adriamycin, daunorubicin, and arabinosylcytosine, due to the expression of MRP. We found that the expression of SKP2 was higher in HL-60/A cells than in HL-60 cells, but the expression of P27kip1 was lower. The expression of SKP2 in HL-60/A cells nucleofected by SKP2 siRNA was down-regulated whereas the protein level of P27kip1 was up-regulated. Compared with the MRP expression level in the control group (nucleofected by control siRNA), the mRNA and protein expression levels of MRP in HL-60/A cells nucleofected by SKP2 siRNA were lower, and the latter cells were more sensitive to adriamycin, daunorubicin, and arabinosylcytosine. Down-regulating the SKP2 expression and arresting cells in the G0/G1 phase improve drug sensitivity of leukemia cells with down-regulated MRP expression.

  L Ma , D Lai , T Liu , W Cheng and L. Guo
 

One emerging model for the development of drug-resistant tumors utilizes a pool of self-renewing malignant progenitors known as cancer stem cells (CSCs) or cancer-initiating cells (CICs). The purpose of this study was to propagate such CICs from the ovarian cancer cell line SKOV3. The SKOV3 sphere cells were selected using 40.0 µmol/l cisplatin and 10.0 µmol/l paclitaxel in serum-free culture system supplemented with epidermal growth factor, basic fibroblast growth factor, leukemia inhibitory factor, and insulin or standard serum-containing system. These cells formed non-adherent spheres under drug selection (cisplatin and paclitaxel) and serum-free culture system. The selected sphere cells are more resistant to cisplatin, paclitaxel, adriamycin, and methotrexate. Importantly, the sphere cells have the properties of self-renewal, with high expression of the stem cell genes Nanog, Oct4, sox2, nestin, ABCG2, CD133, and the stem cell factor receptor CD117 (c-kit). Consistently, flow cytometric analysis revealed that the sphere cells have a much higher percentage of CD133+/CD117+-positive cells (71%) than differentiated cells (33%). Moreover, the SKOV3 sphere cells are more tumorigenic. Furthermore, cDNA microarray and subsequent ontological analyses revealed that a large proportion of the classified genes were related to angiogenesis, extracellular matrix, integrin-mediated signaling pathway, cell adhesion, and cell proliferation. The subpopulation isolation from the SKOV3 cell line under this culture system offers a suitable in vitro model for studying ovarian CSCs in terms of their survival, self-renewal, and chemoresistance, and for developing therapeutic drugs that specifically interfere with ovarian CSCs.

  C Chang , A Uchiyama , L Ma , T Mashimo and Y. Fujino
 

BACKGROUND: Dexmedetomidine, propofol, and midazolam are commonly used sedative-hypnotic drugs. Using a steady-state method, we examined the CO2 ventilatory response, mean arterial blood pressure (MAP) and heart rate (HR) effects of these three drugs in sevoflurane-anesthetized rabbits.

METHODS: New Zealand white rabbits weighing 2.9 ± 0.2 kg (mean ± sd) were used. After anesthetic induction and tracheostomy, the animals inhaled 2% sevoflurane to ensure a stable level of sedation throughout the experiment. After preparation, the rabbits were randomly assigned to four groups (n = 10 x 4) and received the following drugs: Group C, control; Group D, dexmedetomidine infused at 2 µg · kg–1 · h–1; Group P, propofol with the plasma concentration maintained at 15 µg/mL; Group M, midazolam initial IV 0.3 mg/kg bolus dose, followed by infusion at 1.86 mg · kg–1 · h–1. At 15 minutes after the start of infusion, for 20 min periods, in random sequences, gas including 0%, 1%, 2%, 3%, 4%, or 5% of CO2 was delivered to each animal. Fraction of inspired oxygen was maintained at 0.9. We did intergroup comparisons of minute ventilation (MV), respiratory rate, MAP, and HR during the final minute of each inspiratory carbon dioxide concentration (FiCO2) period.

RESULTS: For Groups P and M, the rightward shift of plots for MV against FiCO2 indicated significant respiratory depression compared with Group C. There was also significantly more depression than in Group D. We found no significant differences between Groups P and M or between Groups C and D in the plots of MV against FiCO2. No significant differences among the four groups were apparent for respiratory rate. Paco2-MV response plots were derived from linear regression analysis of data for mean MV and mean Paco2 at each FiCO2 to compute apneic CO2 thresholds and CO2 sensitivities. The apneic CO2 thresholds of Groups P and M were larger than those of Groups C and D. The CO2 sensitivities of Group D were slightly lower than in Group C. No similar significant difference between the CO2 sensitivities of other group pairs was apparent. MAP in Group D was lower than in Groups C and M. In Group D, HR was lower than in Groups C, P, and M.

CONCLUSIONS: The major finding is that, during sevoflurane anesthesia in rabbits, dexmedetomidine slightly altered the ventilatory response to CO2. It decreased MAP more than propofol and midazolam, which both significantly depressed the ventilatory response to CO2.

  F Kassie , S Kalscheuer , I Matise , L Ma , T Melkamu , P Upadhyaya and S. S. Hecht
 

In previous studies, we reported that indole-3-carbinol (I3C) and myo-inositol (MI) inhibit lung adenoma induced by tobacco smoke carcinogens in A/J mice. In this paper, we extended our work and examined the effects of I3C (70 or 30 µmol/g diet) and MI (56 µmol/g diet) against vinyl carbamate (VC)-induced lung adenocarcinoma by administering the agents from 1 week after the second of two injections of VC until termination of the study at week 18. The higher dose of I3C decreased multiplicities of tumors on the surface of the lung (26%, P = 0.0005), carcinoma incidence (38%), multiplicity (67%, P < 0.0001) and size (complete abolition of carcinoma with an area of >1.0 cm2) as well as adenoma with cellular pleomorphism (46%, P < 0.0001). The lower dose of I3C was less effective. MI decreased multiplicities of pulmonary surface tumors (20%, P = 0.0005), adenoma with cellular pleomorphism (40%, P < 0.0001) and lung adenoma (52%, P < 0.0001) and the proportion of the biggest carcinoma (carcinoma with an area of >1.0 cm2, P < 0.05). Immunoblot analyses of lung tissues for potential target identification showed that I3C (70 µmol/g diet) inhibits IkappaB degradation, nuclear factor-kappaB activation, expression of cyclooxygenase-2, phospho-Akt and fatty acid synthase (FAS) and activates caspase-3 and poly ADP ribose polymerase cleavage. The effect of MI was limited to inhibition of phospho-Akt and FAS expression. Our data show that I3C and MI inhibit lung carcinoma and provide a basis for future evaluation of these compounds in clinical trials as chemopreventive agents for current and former smokers.

  J. E Craig , A. W Hewitt , A. E McMellon , A. K Henders , L Ma , L Wallace , S Sharma , K. P Burdon , P. M Visscher , G. W Montgomery and S. MacGregor
 

Genome-wide association studies (GWAS) have now successfully identified important genetic variants associated with many human traits and diseases. The high cost of genotyping arrays in large data sets remains the major barrier to wider utilization of GWAS. We have developed a novel method in which whole blood from cases and controls, respectively, is pooled prior to DNA extraction for genotyping. We demonstrate proof of principle by clearly identifying the associated variants for eye color, age-related macular degeneration, and pseudoexfoliation syndrome in cohorts not previously studied. Blood pooling has the potential to reduce GWAS cost by several orders of magnitude and dramatically shorten gene discovery time. This method has profound implications for translation of modern genetic approaches to a multitude of diseases and traits yet to be analyzed by GWAS, and will enable developing nations to participate in GWAS.

  A. L Bi , Y Wang , B. Q Li , Q. Q Wang , L Ma , H Yu , L Zhao and Z. Y. Chen
 

Actin rearrangement plays an essential role in learning and memory; however, the spatial and temporal regulation of actin dynamics in different phases of associative memory has not been fully understood. Here, using the conditioned taste aversion (CTA) paradigm, we investigated the region-specific involvement of actin rearrangement-related synaptic structure alterations in different memory processes. We found that CTA training could induce increased postsynaptic density (PSD) length in insular cortex (IC), but not in basolateral amygdala (BLA) and prelimbic cortex (PrL) during short-term memory (STM) formation, whereas it led to increased PSD length and synapse density in both IC and PrL during long-term memory (LTM) formation. Inhibition of actin rearrangement in the IC, but not in the BLA and PrL, impaired memory acquisition. Furthermore, actin dynamics in the IC or PrL is necessary for memory consolidation. On the contrary, inhibition of actin dynamics in the IC, BLA, or PrL had no effect on CTA memory retrieval. Our results suggest temporal and regional-specific regulation of actin rearrangement-related synaptic structure in different phases of CTA memory.

  D Cho , M Zheng , C Min , L Ma , H Kurose , J. H Park and K. M. Kim
 

The regulatory mechanisms and functional roles of agonist-induced internalization of G protein-coupled receptors (GPCRs) were analyzed using mutant dopamine D2 receptors (D2Rs) in which all possible GPCR kinase (GRK) phosphorylation sites were mutated or the affinity for β-arrestins was altered. Agonist-induced internalization of D2Rs involved a phosphorylation-dependent component, which was mediated by serine/threonine (S/T) residues in the second loop and T225 in the third loop, and a phosphorylation-independent component. GRK2-mediated enhancement of the internalization and inhibition of D2R signaling did not involve receptor phosphorylation, and only the former required the enzymatic activity of GRK2. The phosphorylation-deficient mutant (D2R-intracellular loop 2/3) recycled more slowly and showed more agonist-induced desensitization than did the wild-type D2R, suggesting that receptor phosphorylation mediates the recycling of the internalized receptors and enhances receptor resensitization. Blockade of the agonist-induced internalization of D2R-intracellular loop 2/3 provoked desensitization as in wild-type D2R, suggesting that certain cellular processes other than receptor dephosphorylation occurring within the endocytic vesicle are responsible for the resensitization of D2R. When dissociation between D2R and β-arrestin was inhibited or when the expression of cellular β-arrestins was decreased, agonist-induced desensitization of D2R did not occur, suggesting that dissociation from β-arrestin is the main cellular process required for resensitization of D2R and is achieved through agonist-induced internalization. These results indicate that, in the regulation of some GPCRs, phosphorylation-independent association with β-arrestin plays a major role in agonist-induced desensitization.

 
 
 
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