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Articles by C Yang
Total Records ( 8 ) for C Yang
  Y Zhao , J Liu , Q Hong , C Yang , L Chen , Y Chen , Q Wang , K Zhao and W. Jin
 

Overexpression of multidrug resistance 1 (MDR1) in cancer remains one of the major causes for the failure of chemotherapy. In the present study, we found that MyoD and PEA3 could activate P-glycoprotein (P-gp) expression in SGC7901 cells. Knockdown of MyoD and PEA3 attenuated MDR1 expression and increased the sensitivity of multidrug resistant cancer cells to cytotoxic drugs that were transported by P-gp in SGC7901/VCR cells. MyoD or PEA3 could bind to the E-box and PEA3 sites on the MDR1 promoter and activate its transcription. The regulation of MDR1 expression by MyoD and PEA3 may provide potential ways to overcome MDR in cancer treatment.

  C Yang , D Ji , E. J Weinstein , E Choy , F. J Hornicek , K. B Wood , X Liu , H Mankin and Z. Duan
 

Osteosarcoma is the most common primary malignant bone tumor affecting children and adolescents. The majority of patients are treated by surgery and chemotherapy but have limited alternative therapeutic options. Kinases play an important role in the growth and survival of tumor cells. We aim to identify specific kinases to be vital in the survival of osteosarcoma cells and thus may be a key target in creating novel anticancer therapies. A lentiviral short hairpin RNA kinase library, screened osteosarcoma cells, identified kinase minibrain-related kinase (Mirk) (Dyrk1B) as a potential target. Knockdown Mirk expression could inhibit cell growth and induce apoptosis. Chemically synthetic small interfering RNA knockdown and complementary DNA rescue assay further confirmed the results from the decrease of Mirk gene expression. The relationship between Mirk gene expression and the clinical characteristics of patients with osteosarcoma was investigated using tissue microarray and immunohistochemistry analysis. The data indicate that the overall survival rate of patients with Mirk high staining (high levels of Mirk protein expression) is significantly shorter than those with Mirk low staining and moderate staining. This highlights Mirk’s potential to serve as a promising target for molecular therapy in the treatment of osteosarcoma.

  C Zhang , C Wang , X Chen , C Yang , K Li , J Wang , J Dai , Z Hu , X Zhou , L Chen , Y Zhang , Y Li , H Qiu , J Xing , Z Liang , B Ren , K Zen and C. Y. Zhang
  BACKGROUND:

Sensitive and specific biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC) are urgently needed to reduce the high morbidity and mortality of the disease. The discovery of serum microRNAs (miRNAs) and their unique concentration profiles in patients with various diseases makes them attractive, novel noninvasive biomarkers for tumor diagnosis. In this study, we investigated the serum miRNA profile in ESCC patients to develop a novel diagnostic ESCC biomarker.

METHODS:

Serum samples were taken from 290 ESCC patients and 140 age- and sex-matched controls. Solexa sequencing technology was used for an initial screen of miRNAs in serum samples from 141 patients and 40 controls. A hydrolysis probe–based stem–loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and verification phases to confirm the concentrations of selected miRNAs in serum samples from 149 patients and 100 controls.

RESULTS:

The Solexa sequencing results demonstrated marked upregulation of 25 serum miRNAs in ESCC patients compared with controls. RT-qPCR analysis identified a profile of 7 serum miRNAs (miR-10a, miR-22, miR-100, miR-148b, miR-223, miR-133a, and miR-127-3p) as ESCC biomarkers. The area under the ROC curve for the selected miRNAs ranged from 0.817 to 0.949, significantly higher than for carcinoembryonic antigen (0.549; P < 0.0005). More importantly, this panel of 7 miRNAs clearly distinguished stage I/II ESCC patients from controls.

CONCLUSIONS:

This panel of 7 serum miRNAs holds promise as a novel blood-based biomarker for the diagnosis of ESCC.

  L Lu , P Li , C Yang , T Kurth , M Misale , M Skelton , C Moreno , R. J Roman , A. S Greene , H. J Jacob , J Lazar , M Liang and A. W. Cowley
 

Chromosome 13 consomic and congenic rat strains were analyzed to investigate the pattern of genomic pathway utilization involved in protection against salt-sensitive hypertension and renal injury. Introgression of the entire Brown-Norway chromosome 13 (consomic SS-13BN) or nonoverlapping segments of this chromosome (congenic strains, 16 Mbp in D13Rat151–D13Rat197 or 14 Mbp in D13Rat111–D13Got22) into the genome of the Dahl salt-sensitive rat attenuated salt-induced hypertension and proteinuria. mRNA abundance profiles in the renal cortex and the renal medulla from rats receiving 0.4% or 8% NaCl diets revealed two important features of pathway recruitment in these rat strains. First, the two congenic strains shared alterations in several pathways compared with Dahl salt-sensitive rats, despite the fact that the genomic segments introgressed in the two congenic strains did not overlap. Second, even though the genomic segment introgressed in each congenic strain was a part of the chromosome introgressed in the consomic strain, pathways altered in each congenic strain were not simply a subset of those altered in the consomic. Supporting the relevance of the mRNA data, differential expression of oxidative stress-related genes among the four strains of rats was associated with differences in urinary excretion of lipid peroxidation products. The findings suggest that different genetic alterations might converge to influence shared pathways in protection from hypertension, and that, depending on the genomic context, the same genetic alteration might diverge to affect different pathways.

  P Zhang , C Yang and R. J. Delay
 

Located at the anterior portion of the nose, the paired vomeronasal organs (VNO) detect odors and pheromones. In vomeronasal sensory neurons (VSNs) odor responses are mainly mediated by phospholipase C (PLC), stimulation of which elevates diacylglycerol (DAG). DAG activates a transient receptor potential channel (TRPC2) leading to cell depolarization. In this study, we used a natural stimulus, urine, to elicit odor responses in VSNs and found urine responses persisted in TRPC2–/– mice, suggesting the existence of a TRPC2-independent signal transduction pathway. Using perforated patch-clamp recordings on isolated VSNs from wild-type (WT) and TRPC2–/– mice, we found a PLC inhibitor blocked urine responses from all VSNs. Furthermore, urine responses were reduced by blocking DAG lipase, an enzyme that produces arachidonic acid (AA), in WT mice and abolished in TRPC2–/– mice. Consistently, direct stimulation with AA activated an inward current that was independent of TRPC2 channels but required bath Ca2+ and was blocked by Cd2+. With the use of inside-out patches from TRPC2–/– VSNs, we show that AA activated a channel that also required Ca2+. Together, these data from WT and TRPC2–/– mice suggest that both DAG and its metabolite, AA, mediate excitatory odor responses in VSNs, by activating two types of channels, a TRPC2 and a separate Ca2+-permeable channel.

  C. G Rios , R. R Leger , M. P Cote , C Yang and R. A. Arciero
 

Background: Injuries to the posterolateral corner of the knee remain a challenging problem and have been cited frequently as a reason for failure of anterior and posterior cruciate ligament reconstructions. Although several reconstructive techniques currently exist, there are relatively few clinical outcomes data after reconstruction of the posterolateral corner.

Purpose: The study was undertaken to examine the clinical outcomes and provide objective data using arthrometry and stress radiography of a posterolateral corner reconstruction technique.

Study Design: Case series; Level of evidence, 4.

Methods: A retrospective cohort study of a consecutive series of patients who underwent posterolateral corner reconstruction of the knee was evaluated. The surgery featured dual femoral tunnels, a transfibular tunnel, and a free graft to reconstruct the posterolateral corner of the knee. All patients had concomitant reconstruction of one or both cruciate ligaments. Outcomes were assessed using the Short Form–12, Lysholm, and Tegner knee scores. A clinical examination, KT-2000 arthrometry measurements, single-legged hop quotient, and varus and posterior Telos stress radiographs were obtained and compared with results for the contralateral, uninjured knees.

Results: Twenty-four (83%) of 29 consecutive patients were evaluated at a mean 39 months postoperatively (range, 24-81 months). The mean Lysholm and Tegner knee scores were 83 and 6, respectively. The mean difference (± standard deviation) in total anterior-posterior side-to-side KT arthrometry measurements was 1.4 ± 1.3 mm. The varus stress radiographic mean side-to-side difference measured at 20° of flexion was 0.2 ± 1.9 mm. The mean radiographic posterior tibial displacement with a 15-kg stress at 90° of flexion was 3.2 ± 4.5 mm in patients undergoing posterior cruciate ligament reconstruction.

Conclusion: This reconstruction of the posterolateral corner of the knee with concomitant cruciate ligament reconstruction restores varus and rotational stability at a minimum of 2 years postoperatively.

  J. M Benjamin , A. V Kwiatkowski , C Yang , F Korobova , S Pokutta , T Svitkina , W. I Weis and W. J. Nelson
 

E-catenin has cell–cell contact–dependent and –independent functions in regulating actin and membrane dynamics.

  C Yang and R. J. Delay
 

The vomeronasal organ (VNO) is an odor detection system that mediates many pheromone-sensitive behaviors. Vomeronasal sensory neurons (VSNs), located in the VNO, are the initial site of interaction with odors/pheromones. However, how an individual VSN transduces chemical signals into electrical signals is still unresolved. Here, we show that a Ca2+-activated Cl current contributes ~80% of the response to urine in mouse VSNs. Using perforated patch clamp recordings with gramicidin, which leaves intracellular chloride undisrupted, we found that the urine-induced inward current (Vhold = –80 mV) was decreased in the presence of chloride channel blockers. This was confirmed using whole cell recordings and altering extracellular chloride to shift the reversal potential. Further, the urine-induced currents were eliminated when both extracellular Ca2+ and Na+ were removed. Using inside-out patches from dendritic tips, we recorded Ca2+-activated Cl channel activity. Several candidates for this Ca2+-activated Cl channel were detected in VNO by reverse transcription–polymerase chain reaction. In addition, a chloride cotransporter, Na+-K+-2Cl isoform 1, was detected and found to mediate much of the chloride accumulation in VSNs. Collectively, our data demonstrate that chloride acts as a major amplifier for signal transduction in mouse VSNs. This amplification would increase the responsiveness to pheromones or odorants.

 
 
 
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