Zhihui Yang

Identification of serum biomarkers for nasopharyngeal carcinoma by proteomic analysis.

Early diagnosis of nasopharyngeal carcinoma (NPC) remains a challenge. Serum protein profiling is a promising approach for the classification of cancer versus noncancer samples. The objective of the current study was to assess the feasibility of mass spectrometry‐based protein profiling and a classification tree algorithm for discriminating between patients with NPC and noncancer controls.

The xeroderma pigmentosum group C gene polymorphisms and genetic susceptibility of nasopharyngeal carcinoma

Aims. Nasopharyngeal cancer (NPC) is a multi-factorial disease, and the genetic background may be a crucial etiologic factor. The xeroderma pigmentosum complementation group C (XPC) is mainly involved in DNA damage repair, and the sequence variants in XPC gene may modulate DNA repair capacity and consequently lead to an individuals susceptibility to NPC. The aims of this study were to examine the association between XPC Val499Ala, Lys939Gln, PAT polymorphisms and the genetic susceptibility of nasopharyngeal carcinoma (NPC) in Chinese population. Methods. We analyzed the three XPC gene polymorphisms in 153 patients with NPC and 168 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. Results. There were significant differences in the genotype and allele distribution of XPC Val499Ala among cases and controls. The 499Val allele carriers were associated with a significantly increased risk of NPC compared with the non-carriers (OR=1.603; 95%CI, 1.160∼2.216, p=0.005). Consistent with the results of the genotype analysis, the 499Val/939Lys/PAT–haplotype was associated with a significantly increased risk of NPC as compared with the 499Ala/939Lys/PAT–haplotype (OR=1.901; 95% CI, 1.284∼2.814, p=0.002).The interaction between the Val499Ala polymorphism and gender or smoking status did not been found in NPC risk. Conclusions. Our data demonstrated that XPC 499Val allele and its haplotype were strongly associated with NPC, which indicated that Val499Ala polymorphism may be a contributing factor in the NPC development.

Construction and Preliminary Investigation of a Plasmid Containing a Novel Immunotoxin DT390-IL-18 Gene for the Prevention of Murine Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a neuropathological animal model for multiple sclerosis. Antigen-presenting cells (APCs) expressing interleukin-18 receptor (IL-18R) were shown to be crucial in the beginning and progress of EAE. In this study we tested the effect of a novel recombinant immunotoxin targeting IL-18R-bearing APC for EAE prevention. The novel eukaryotic plasmid DT390-IL-18-SRalpha, encoding recombinant immunotoxin DT390-IL-18, was constructed. The immunotoxin consisted of IL-18 as the targeting moiety, and a truncated diphtheria toxin (DT) as the toxic moiety. Transfection assay and proliferation inhibition assay proved the immunotoxin could be expressed in vitro and was toxic to the activated mouse T cells. To evaluate the preventive effect of DT390-IL-18-SRalpha on EAE in vivo, cationic liposome-embedded DT390-IL-18-SRalpha was injected into the hind limbs of EAE mice. DT390-IL-18-SRalpha-treated mice showed a delayed manifestation of EAE and decreased symptoms compared to the mice treated with plasmid DT390-SRalpha or phosphate-buffered saline alone. A significant reduction in infiltrating inflammatory cells was detected in the brain tissues from immunotoxin-treated mice as compared with the controls by hematoxylin-eosin staining. This study suggested that the recombinant immunotoxin DT390-IL-18 could be expressed in vitro and in vivo, and prevented murine EAE effectively.

Abstract A25: Variations of human papillomavirus type 16 in cervical, lung, and skin cancers in Sichuan, China

Human papillomavirus (HPV) is closely related with many kinds of cancers such as cervical, lung, and skin cancers, etc. HPV 16 showed intratypic variations that were known to differ in oncogenic potential and geographic distribution. This study was designed to analyze sequence variants in oncogenes E6, E7 and L1 of HPV 16 in cervical, lung, and skin cancers in Sichuan, China. Materials from 138 non-malignant controls, 122 cervical cancer patients, 104 lung cancer patients and 104 skin cancer patients were analyzed by PCR and direct sequencing. The infection rates of HPV 16 in cervical, lung, skin cancers were respectively 68.9%, 17.3%, 5.8%. The Asian prototype was the most prevalent variant in cervical cancer in Sichuan (40%). Compared with that detected in cervical cancer, lung and skin cancers showed more monotonous variations, but several mutations on L1 genes existed only in lung or skin cancers such as G6818C, C7011A, and C7017A. Citation Information: Clin Cancer Res 2010;16(14 Suppl):A25.