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Jian-Jun Chen

Publications and source records attributed to Jian-Jun Chen.

26 records · Page 2Linked to original sources
PubMed2004

Identification of the cylindromatosis tumor-suppressor gene responsible for multiple familial trichoepithelioma.

Multiple familial trichoepithelioma (MFT) is an autosomal dominant skin disease characterized by the presence of many small benign tumors with pilar differentiation predominantly on the face. The first locus has been previously mapped to chromosome 9p21, but no gene for MFT has been identified to date. To identify the disease gene in a large Chinese family, we initially performed linkage analysis with microsatellite markers from 9p21, but failed to confirm the linkage to this region. Previous publications showed MFT and familial cylindromatosis (FC) can occur within one family and in a single person. Therefore, we speculated that the cylindromatosis gene (CYLDI gene) responsible for FC may be related to the pathogenesis of MFT. In view of that, we genotyped all available individuals using 11 microsatellite markers spanning the CYLDI gene region at 16q12-q13. We identified the linkage of MFT to this region. Mutation analysis in the CYLDI gene detected a frameshift mutation, designated as c.2355-2358delCAGA. The study firstly identified the cylindromatosis gene responsible for MFT and showed that different mutations of the CYLDI gene can give rise to distinct clinical and histological expression such as FC and MFT.

Adolescent↗
PubMed2003

Tumor-derived TGF-beta reduces the efficacy of dendritic cell/tumor fusion vaccine.

Dendritic cell (DC)-based antitumor vaccine is a novel cancer immunotherapy that is promising for reducing cancer-related mortality. However, results from early clinical trials were suboptimal. A possible explanation is that many tumors secrete immunosuppressive factors such as TGF-beta, which may hamper host immune response to DC vaccine. In this study, we demonstrated that TGF-beta produced by tumors significantly reduced the potency of DC/tumor fusion vaccines. TGF-beta-secreting (CT26-TGF-beta) stable mouse colon cancer cell lines were generated using a retroviral vector expressing TGF-beta. A non-TGF-beta-secreting (CT26-neo) cell line was generated using an empty retroviral vector. The efficacies of DC/tumor fusion vaccines were assessed in vitro and in vivo. DC/CT26-TGF-beta fusion cells failed to induce a strong T cell proliferative response in vitro, mainly due to the effect of TGF-beta on T cell responsiveness rather than DC stimulatory capability. Animals vaccinated with DC/CT26-TGF-beta fusion vaccine had lower tumor-specific CTL activity and had significantly lower survival after tumor challenge as compared with animals immunized with DC/CT26-neo hybrids (45 vs 77%, p < 0.05). Ex vivo exposure of DCs to TGF-beta did not appear to lessen the efficacy of DC vaccine. These data suggest that tumor-derived TGF-beta reduces the efficacy of DC/tumor fusion vaccine via an in vivo mechanism. Neutralization of TGF-beta produced by the fusion cells may enhance the effectiveness of DC-based immunotherapy.

Animals↗
PubMed2003

A mutation in the connexin 30 gene in Chinese Han patients with hidrotic ectodermal dysplasia.

BACKGROUND: hidrotic ectodermal dysplasia (HED) or Clouston syndrome is a rare autosomal dominant disorder affecting the skin and its derivatives. It is characterized by the triad of nail dystrophy, alopecia, and palmoplantar hyperkeratosis. To date, all mutations have been involving in three codons: G11R, A88V and V37E in the connexin 30 (Cx30) gene have been shown to cause this disorder. OBJECTIVE: in order to analyze the mutations of the Cx30 gene in Chinese Han patients with HED. METHODS: we collected a large Chinese HED family consisting of a total of 81 individuals including 28 HED patients (14 males and 14 females). The whole coding region of Cx30 was amplified by polymerase chain reaction and products analyzed by direct sequencing, then further confirmed at the mRNA level by RT-PCR. RESULTS: we detected a transition, 31(G-->A), leading to a missense mutation (G11R) in genomic DNAs of 18 patients, and the point mutation was not found in 16 normal individuals in this HED family and in 188 unrelated, population-match control individuals. The transcription of mutated allele was confirmed by RT-PCR of Cx30 mRNA. CONCLUSION: our data suggests that a G11R missense mutation in the Cx30 gene can cause HED in Chinese Han population and emphasizes the importance of screening for this as well as other Cx30 gene mutations in the HED.

Adult↗
PubMed2003

Association of HLA class I alleles with psoriasis vulgaris in southeastern Chinese Hans.

BACKGROUND: Predisposing genetic factors in psoriasis include associations with human leukocyte antigen (HLA). Accumulative evidence has shown that certain HLA at class I locus, especially HLA-Cw6, are associated closely with psoriasis. OBJECTIVE: To evaluate the association of HLA class I alleles with susceptibility to psoriasis in the southeastern Chinese Han population. METHODS: We performed genotype for HLA-A, -B and -C loci in 166 patients with psoriasis vulgaris by means of polymerase chain reaction with sequence-specific primers technique. The distribution of HLA allelic frequencies was further analyzed according to age of onset, i.e. under 35-y and beyond 35-y groups. These data were compared with the healthy controls of 204 unrelated Hans. RESULTS: The frequencies of HLA-A*26 (24.7% vs. 13.1%, OR=2.36, Pc<0.01), -B*13 (27.2% vs. 14.8%, OR=2.34, Pc<0.01), -B*27 (12.2% vs. 4.0%, OR=3.49, Pc<0.01) and -Cw*0602 (17.9% vs. 5.3%, OR=4.20, Pc<0.001) were significantly increased in psoriasis patients, whereas HLA-Cw*0304 frequency (4.9% vs. 13.4%, OR=0.32, Pc<0.01) was highly decreased, when compared to the controls. HLA-A*26-B*27-Cw*0602 was identified as a high-risk haplotype of HLA class I in developing psoriasis in the test. HLA-Cw*0602 was found to be strongly associated with the early-onset psoriasis (age of onset <35 y). CONCLUSION: This study demonstrated the positive associations of HLA class I markers with psoriasis vulgaris, of which HLA-Cw*0602 was the strongest susceptibility determinant for development of early-onset psoriasis, in the southeastern Chinese Han population.

Adult↗
PubMed1999

Construction and Expression of hTNFalpha-hTGF3 Fused Gene.

Human tumor necrosis factor was fused with hTGF3, the third loop region of hTGFalpha specifically binding to EGF receptor, through a flexible linker by recombinant DNA techniques. The constructed plasmid containing hTNFalpha-hTGF3 fused gene, pSB92-TLT, was expressed under the control of P(L) promoter and after the induction at 42 degrees it gave a high level of expression of the fused gene, ranging in 50%-60% of total bacterial protein. 95% of the expressed product was inclusion body, and only 5% was soluble. When the fused gene was constructed into the constitutive plasmid pLC, a new plasmid controlled by P(L) promoter but without cIts857, and expressed at 30 degrees, the expression yield reached 50% and a high proportion of soluble protein, 35% of total bacterial protein, was obtained. Western blot analysis indicated that the fusion protein could specifically bind to anti-hTNFalpha antibody. Comparing to original hTNFalpha, the fused hTNFalpha derivative showed about equal cytotoxicity to L929 cell line and higher cytotoxicity to some human tumor cell lines. This shows that the fusion protein TLT may be promising in application.

Journal Article↗