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Articles by Z Hong
Total Records ( 3 ) for Z Hong
  Z Hong , M Shi , K. A Chung , J. F Quinn , E. R Peskind , D Galasko , J Jankovic , C. P Zabetian , J. B Leverenz , G Baird , T. J Montine , A. M Hancock , H Hwang , C Pan , J Bradner , U. J Kang , P. H Jensen and J. Zhang
 

Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinson’s disease. Both DJ-1 and -synuclein, two proteins critically involved in Parkinson’s disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein species detected by different antibodies, limited numbers of patients in some studies, or inadequate control of several important variables. In this study, the nature of DJ-1 and -synuclein in human cerebrospinal fluid was studied by a combination of western blotting, gel filtration and mass spectrometry. Sensitive and quantitative Luminex assays detecting most, if not all, species of DJ-1 and -synuclein in human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of DJ-1 and -synuclein from 117 patients with Parkinson’s disease, 132 healthy individuals and 50 patients with Alzheimer’s disease were analysed using newly developed, highly sensitive Luminex technology while controlling for several major confounders. A total of 299 individuals and 389 samples were analysed. The results showed that cerebrospinal fluid DJ-1 and -synuclein levels were dependent on age and influenced by the extent of blood contamination in cerebrospinal fluid. Both DJ-1 and -synuclein levels were decreased in Parkinson’s patients versus controls or Alzheimer’s patients when blood contamination was controlled for. In the population aged ≥65 years, when cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and -synuclein, respectively, the sensitivity and specificity for patients with Parkinson’s disease versus controls were 90 and 70% for DJ-1, and 92 and 58% for -synuclein. A combination of the two markers did not enhance the test performance. There was no association between DJ-1 or -synuclein and the severity of Parkinson’s disease. Taken together, this represents the largest scale study for DJ-1 or -synuclein in human cerebrospinal fluid so far, while using newly established sensitive Luminex assays, with controls for multiple variables. We have demonstrated that total DJ-1 and -synuclein in human cerebrospinal fluid are helpful diagnostic markers for Parkinson’s disease, if variables such as blood contamination and age are taken into consideration.

  Z Han , Z Hong , C Chen , Q Gao , D Luo , Y Fang , Y Cao , T Zhu , X Jiang , Q Ma , W Li , L Han , D Wang , G Xu , S Wang , L Meng , J Zhou and D. Ma
 

Tumor cells acquire the ability to proliferate uncontrollably, resist apoptosis, sustain angiogenesis and evade immune surveillance. Signal transducer and activator of transcription (STAT) 3 regulates all of these processes in a surprisingly large number of human cancers. Consequently, the STAT3 protein is emerging as an ideal target for cancer therapy. This paper reports the generation of an oncolytic adenovirus (M4), which selectively blocks STAT3 signaling in tumor cells as a novel therapeutic strategy. M4 selectively replicated in tumor cells and expressed high levels of antisense STAT3 complementary DNA during the late phase of the viral infection in a replication-dependent manner. The viral progeny yield of M4 in tumor cells was much higher than that of the parent adenoviral mutants, Ad5/dE1A. M4 effectively silenced STAT3 and its target genes in tumor cells while sparing normal cells and exhibited potent antitumoral efficacy in vitro and in vivo. Systemic administration of M4 significantly inhibited tumor growth in an orthotopic gastric carcinoma mouse model, eliminated abdominal cavity metastases and prolonged survival time. In summary, M4 has low toxicity and great potential as a therapeutic agent for different types of cancers.

 
 
 
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