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Association of XPC gene polymorphisms with breast cancer risk.

Yin-yin WU ; Xin-yuan MA ; Kai-yan YAO ; Qi-long LI ; Kun CHEN

Journal of Zhejiang University. Medical sciences.2011;40(3):252-258.

OBJECTIVETo access the association of xeroderma pigmentosum group C (XPC) Lys939Gln (A/C) and Ala499Val (C/T) polymorphisms with breast cancer risk in a Chinese Han population.

METHODS173 patients with breast cancer and 171 matched controls in terms of habitation and age (±5 years) were included in this population-based case-control study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was employed to genotyping the Lys939Gln and Ala499Val polymorphisms. Associations of genotypes of Lys939Gln and Ala499Val with breast cancer risk were evaluated using unconditional logistic regression model. Associations between XPC haplotypes and breast cancer risk were estimated by Haplo. Stats package.

RESULTNo significant associations were observed both in individual SNPs and haplotype analyses. However, there was a significant interaction between XPC Lys939Gln polymorphism and menopausal status (P=0.032).

CONCLUSIONThe XPC Lys939Gln polymorphism may modulate breast cancer susceptibility jointly with the menopausal status.

Adolescent ; Adult ; Breast Neoplasms ; genetics ; Case-Control Studies ; DNA-Binding Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Menopause ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk ; Young Adult

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Expression of caspase apoptosis pathway genes mRNA in colorectal cancer and polyps.

Yi-feng PAN ; Ming-wu ZHANG ; Ming-juan JIN ; Shan-chun ZHANG ; Kun CHEN ; Qi-long LI ; Xin-yuan MA ; Kai-yan YAO ; Yun-xian YU

Journal of Zhejiang University. Medical sciences.2011;40(3):245-251.

OBJECTIVETo investigate mRNA expression of caspase apoptosis pathway genes in colorectal cancer, polyps and normal mucosa.

METHODSNineteen patients with colorectal cancer, 86 patients with polyps and 10 normal controls were enrolled from 2008 to 2010. Fluorescence quantitative RT-PCR was performed to detect the mRNA expression of caspase apoptosis pathway genes (caspase-2,-3,-6,-7,-8,-9 and -10) in colorectal cancer, polyps and normal mucosa.

RESULTThere were no statistically significant differences of demographic characteristics between patients with colorectal cancer, patients with polyps and normal controls. Compared with normal control group, the mRNA expression of all selected genes except for caspase-3 were lower; however, the P values did not reach statistic significance. Highly positive correlations were observed between mRNA expression of all selected genes except caspase-9.

CONCLUSIONThere are no significant changes in mRNA expression levels of caspase apoptosis pathway genes from normal mucosa to polyps to cancer. The mRNA expressions of most caspase pathway genes are highly correlated with each other.

Aged ; Caspases ; genetics ; metabolism ; Colorectal Neoplasms ; genetics ; metabolism ; Female ; Gene Expression ; Humans ; Intestinal Mucosa ; metabolism ; Intestinal Polyps ; genetics ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

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Screening of Tag SNPs and prediction of their potential function in genetic studies of complex diseases.

Yi-min ZHU ; Yu-yang XU ; Jie LING

Journal of Zhejiang University. Medical sciences.2011;40(3):237-244.

We applied public databases of single nucleotide polymorphism (SNP) to screen complex disease-related SNPs and assessed the potential functions of selected SNPs through SNP function prediction software, including FastSNP, SNP Function Prediction, F-SNP. We selected Tag SNP in HapMap database and compared all results with above software. With above strategies we screened IGFBP7 gene and obtained total 47 SNPs, including 11 TFBS SNPs, 31 intronic enhancer SNPs, 4 intronic enhancer and TFBS SNPs and 1 splicing sites SNPs.
Databases, Genetic ; Humans ; Insulin-Like Growth Factor Binding Proteins ; genetics ; Polymorphism, Single Nucleotide ; Software

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Screening strategies for colorectal cancer.

Kun CHEN ; Ming-juan JIN

Journal of Zhejiang University. Medical sciences.2011;40(3):233-236.

Colorectal Neoplasms ; diagnosis ; epidemiology ; Humans ; Mass Screening ; methods

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Toll-like receptors and their role in pathogenesis and vaccine study of cutaneous diseases.

Wei-Wei ZHANG ; Xiao-Hong MAO

Journal of Zhejiang University. Medical sciences.2011;40(2):222-229.

Toll like receptor (TLR) can specifically recgnize pathogen-associated molecular patterns (PAMPs) and is considered as an important link between innate and adaptive immunity. It has been shown that TLR plays an important role in the pathogenesis and pathophysiology of a variety of skin diseases. Moreover, TLR agonists have exhibited promising therapeutic effects on the disease models and are expected to be novel vaccine adjuvants. Investigations of the underlying mechanism will give new insights into these diseases. This review will discuss the relationship between TLR and pathogenesis and management of some cutaneous diseases.
Adaptive Immunity ; Immunity, Innate ; Signal Transduction ; Skin Diseases ; immunology ; metabolism ; Toll-Like Receptors ; immunology ; metabolism ; physiology

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Role of voltage-sodium channels in neuropathic pain.

Wen-Ting SHOU ; Shi-Hong ZHANG ; Zhong CHEN

Journal of Zhejiang University. Medical sciences.2011;40(2):217-221.

Voltage-gated sodium channels are critical for the generation and conduction of nerve impulses. Recent studies show that in primary sensory neurons, the expression and dynamic regulation of several sodium channel subtypes play important roles in neuropathic pain. A number of SCN9A (encoding Nav1.7) gene point mutations are related with human genetic pain disorders. Transgenic and specific knockout techniques have revealed that Nav1.3, Nav1.8, Nav1.9 are important for the development and maintenance of neuropathic pain condition. Specific blockers of these sodium channels have been demonstrated to be effective in alleviating allodynia and hyperalgesia. Here we reviewed the roles of sodium channels in neuropathic pain, which may be applicable for the development of new drugs with enhanced efficacy for neuropathic pain treatment.
Animals ; Humans ; Neuralgia ; genetics ; metabolism ; physiopathology ; Neurons ; metabolism ; physiology ; Sodium Channels ; genetics ; metabolism ; physiology

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Glycometabolism of patients with depression at first episode.

Qing-Chun XIA ; Gao-Hua WANG ; Hai-Zhi CHEN ; Xiao-Yun CHEN ; Wan-Qiu NA

Journal of Zhejiang University. Medical sciences.2011;40(2):213-216.

OBJECTIVETo investigate glycometabolism of patients with depression at first episode.

METHODSOral glucose tolerance test (OGTT) was performed in 100 patients with depression at first episode and 50 healthy subjects; the levels of fast blood plasma insulin were also measured.

RESULTThere were no statistically significant differences in fast blood plasma insulin levels and postprandial blood glucose levels at 0 h, 1 h and 3 h (P>0.05); the fasting blood glucose (FBS), postprandial blood glucose levels in 2 h and area under OGTT curve of depression patients were significantly higher than those of healthy controls. The frequency of impaired glucose tolerance (IGT) in depression patients was higher than that in controls (P<0.05).

CONCLUSIONDepression patients at the first episode are abnormal in glycometabolism, which may have clinical implication.

Adolescent ; Adult ; Aged ; Blood Glucose ; metabolism ; Case-Control Studies ; Depressive Disorder ; blood ; complications ; Female ; Glucose Intolerance ; complications ; Glucose Tolerance Test ; Humans ; Male ; Middle Aged ; Young Adult

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Activation of calcium-sensing receptors is associated with apoptosis in cardiomyocytes under simulated ischemia/reperfusion.

Ling YAN ; Tie-Bing ZHU ; Ting-Ting SUN ; Shi-Yang PAN ; Lain-Sheng WANG ; Zheng-Xian TAO ; Zhi-Jian YANG ; Ke-Jiang CAO

Journal of Zhejiang University. Medical sciences.2011;40(2):207-212.

OBJECTIVETo examine the association of activation of calcium-sensing receptors (CaSR) with apoptosis in cardiomyocytes under simulated ischemia/reperfusion.

METHODSVentricular cardiomyocytes of neonatal rats were incubated in ischemia-mimetic solution for 2 h, then re-incubated in normal culture medium for 24 h to establish a model of simulated ischemia/reperfusion (I/R). Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay). The expression of CaSR mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of Caspase -3 and Bcl-2 was detected by Western blotting.

RESULTThe simulated I/R enhanced the expression of CaSR and cardiomyocyte apoptosis. GdCl(3), a specific activator of CaSR, further increased the expression of CaSR and cardiomyocyte apoptosis, along with upregulation of Caspase-3 and downregulation of Bcl-2.

CONCLUSIONCaSR is associated with I/R injury and apoptosis in neonatal rat ventricular cardiomyocytes via suppressing Bcl-2 and promoting Caspase -3 expression.

Animals ; Apoptosis ; physiology ; Caspase 3 ; metabolism ; Cells, Cultured ; Myocardial Reperfusion Injury ; metabolism ; pathology ; Myocytes, Cardiac ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Receptors, Calcium-Sensing ; metabolism ; Signal Transduction

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Expression of high mobility group box chromosomal protein 1 in mice with lupus nephritis.

Jian-Guang ZHOU ; Jing-Yin DONG ; Li-Huang ZHANG ; Jing WANG

Journal of Zhejiang University. Medical sciences.2011;40(2):200-206.

OBJECTIVETo determine the role of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 (HMGB-1) in the pathogenesis of lupus nephritis.

METHODSSerum levels of anti-dsDNA antibodies were determined by enzyme linked immunosorbent assay (ELISA). Renal morphologic features were examined by light microscopy, electron microscopy, and immunohistologic analyses. The mRNA expression of HMGB-1 and monocyte chemoattractant protein-1 (MCP-1) was detected by RT-PCR.

RESULTMRL/lpr mice demonstrated characteristic alterations of serum immune parameters, with progressively increased anti-dsDNA antibodies with age, compared with age-matched C57BL/6J mice. MRL/lpr mice showed progressive development of renal damage, starting at 12 weeks of age and reached the peak at 20 weeks. The observed lesions included the presence of enlarged hypercellular glomeruli, with increased numbers of both resident cells and infiltrating leukocytes. Higher expression of HMGB-1 mRNA was found in MRL/lpr mice than what in C57BL/6J mice. Expression of HMGB-1 was positively correlated with that of MCP-1 mRNA.

CONCLUSIONThe results demonstrate that the higher expression of HMGB-1 may contribute to the pathogenesis of lupus nephritis.

Animals ; Chemokine CCL2 ; metabolism ; Disease Models, Animal ; HMGB1 Protein ; genetics ; metabolism ; Kidney ; metabolism ; pathology ; Lupus Nephritis ; metabolism ; pathology ; Mice ; Mice, Inbred MRL lpr ; RNA, Messenger ; genetics

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Serum IL-18 levels in mice with collagen-induced arthritis treated by recombinant adenovirus containing mIL-18BP and mIL-4 fusion gene.

Jian-Hang LENG ; Hang-Ping YAO ; Jun-Ya SHEN ; Ke-Yi WANG ; Zi-Wei WANG ; Guang-Chao ZHUO

Journal of Zhejiang University. Medical sciences.2011;40(2):195-199.

OBJECTIVETo investigate serum IL-18 levels in mice with collagen-induced arthritis treated by recombinant adenoviral vector containing mIL-18BP and mIL-4 fusion gene (AdmIL-18BP/mIL-4).

METHODSArthritis was induced by injection of collagen in male DBA-1/BOM mice. Mice with collagen-induced arthritis (CIA) were intra-articularly injected with 10(7)pfu/6μL of AdmIL-18BP/mIL-4; and in mice of control groups AdLacZ or PBS were used. The animals were sacrificed at week 1, 2 and 4 after treatment. Serum IL-18 levels were determined by ELISA at the different time points.

RESULTThe mean serum levels of IL-18 at weeks 1, 2, and 4 after injection of AdmIL-18BP/mIL-4 were (36.5±5.4)ng/L, (32.5 ± 3.2) ng/L and (28.7 ±2.9)ng/L, respectively, which were significantly lower than those at the same time point of AdLacZ group [(66.2 ±5.1)ng/L, (69.2 ±4.2)ng/L and (77.7 ±3.9)ng/L] and PBS group [(67.3 ±7.1)ng/L, (71.9 ±1.8)ng/L and (78.7±4.1)ng/L] (P<0.01 at all time points). In the therapy group, there were no significant differences in the mean serum concentrations of IL-18 at all time points.

CONCLUSIONThe serum IL-18 levels in CIA mice are down-regulated by treatment of recombinant adenovirus containing mIL-18BP and mIL-4 fuse gene, which might be a promising therapeutic strategy for rheumatoid arthritis.

Adenoviridae ; genetics ; Animals ; Arthritis, Experimental ; blood ; therapy ; Gene Fusion ; Genetic Therapy ; Genetic Vectors ; Interleukin-18 ; blood ; genetics ; Interleukin-4 ; genetics ; Male ; Mice ; Mice, Inbred DBA

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