Porcine transcription factor AP-2δ promotes porcine circovirus type 2 replication through enhancing the activity of the rep gene promoter / 生物工程学报

Several putative transcription factor binding sites (TFBSs) exist in the PCV2 rep gene promoter. To explore if porcine circovirus type 2 (PCV2) could regulate the viral replication by using these TFBSs, we conducted electrophoretic mobility shift assay (EMSA), DNA-pull down and liquid chromatography-tandem mass spectrometric (LC-MS/MS) assays. EMSA confirmed the binding activity of the rep gene promoter with nuclear proteins of host cells. DNA-pull down and LC-MS/MS identified the porcine transcription factor AP-2δ (poTFAP2δ) could bind the PCV2 rep gene promoter. Dual-luciferase reporter assay, quantitative real-time PCR, Western blotting and indirect immunofluorescent assay demonstrated that poTFAP2δ could not only promote the activity of the rep gene promoter, but also enhance the transcription/translation activity of the rep/cap gene and the virus titer of PCV2 during the entire life cycle of PCV2 infection. This study revealed the molecular mechanism of PCV2 using host proteins to enhance the viral replication, provided a new perspective for studying the pathogenic mechanism of PCV2 from virus and host interactions, and provided a theoretical basis for developing highly effective PCV2 vaccines.

Study on promoter methylation of PCDHA13 gene and breast cancer development / 医学研究生学报

Objective The mechanisms of PCDHA13 promoter methylation in breast cancer have not yet been elucidated at present. This study was to investigate the role of PCDHA13 gene promoter methylation in the development of breast cancer.Methods The methylation state of PCDHA13 gene promoter in human breast cancer tissues was detected by MassARRAY mass spectrum methylation sequencing. 100μmol/L 5-Aza was prepared with culture medium. The ZR-75-1 cells with 60% cell confluence were added to the final concentration of 5 μmol/L(low concentration group) and 10 μmol/L(high concentration group) 5-Aza, and the control group was only added culture medium. Detection of methylation status of PCDHA13 gene promoter in human breast cancer cells by bisulfite sequencing and methylation-specific PCR, and analysis of methylation status and mRNA expression of PCDHA13 gene by semi-quantitative RT-PCR. Western blot, MTT and DAPI staining were used to detect the effect of 5-Aza treatment on proliferation and apoptosis of breast cancer ZR-75-1 cells.Results The methylation degree of PCDHA13 gene promoter in the 1, 4-6, 9, 10 and 11 CpG loci in breast cancer tissues was significantly higher than that in normal breast group \[(0.2639±0.1575) vs (0.1612±0.1706), (0.2509±0.1377) vs (0.1688±0.0992), (0.4204±0.2087) vs (0.2621±0.1731), (0.3761±0.1407) vs (0.2824±0.1486), (0.3922±0.1294) vs (0.3072±0.1496)\], and the difference was statistically significant (P0.05). The expression of PCDHA13 mRNA of ZR-75-1 cells was loss in control group, but the expression of PCDHA13 mRNA was reversed after treated with 5-Aza, and the expression of PCDHA13 mRNA was significantly higher in high concentration group than that in low concentration group(P>0.05). After treated with 5-Aza for 24, 48 and 72 hours, the growth inhibition rates were lower in low concentration group than that in high concentration group (P>0.05). The morphology of the nuclei was basically normal and there was no apoptosis occurred in ZR-75-1 cells. But after treated with 5-Aza, some ZR-75-1 cells showed nuclear condensation, chromatin agglutination and heavy coloration.Conclusion This study showed that the low expression or loss of mRNA is associated with hypermethylation of the PCDHA13 gene promoter in breast carcinoma. The PCHDA13 gene expression can be reversed by 5-Aza in ZR-75-1 cells. The re-expression of PCHAD13 not only inhibit the proliferation of cells, but also promote apoptosis. Abnormal methylation of PCDHA13 may become a potential tumor marker for breast cancer.

Associations of SYK Promoter-803A ＞T(rs290987) Single Nucleotide Polymorphisms with Susceptibility to Breast Cancer of Han Female Population in Beijing Area / 现代检验医学杂志

Objective To evaluate the association of the SYK gene promoter-803A T polymorphism and breast cancer sus ceptibility during Han descent female population in Beijing area.Methods In this case control study,genotype of SYK (A＞T at-803,rs290987) was determined by polymerase chain reaction combined with DNA direct sequencing in blood samples of 57 breast cancer cases and 60 age matched bealthy controls.They were all female.Genotype and allele frequency distribu tions of 803A T were determined and analyzed.ELISA test was performed to detect the serum level of SYK in the two groups.Results The frequencies of the T allele and TA+TT genotypes of the 803A＞T were found to be significantly higher in the breast cancer patients in contrast to the healthy individuals of the control group(x2 =5.348,P=0.021).Pa tients with the T allele (TA+TT) had a 2.87-fold risk of developing breast cancer compared with those with the A allele (AA) (OR=2.87;95％ CI=1.27～6.49).The test group had significantly decreased level of SYK in serum compared to normal controls (F 33.278,P＜0.01).Conclusion This study revealed that the genotype TA and TT of the SYK gene-803 loci of Han female population in the Beijing area are the risk factors for the breast cancer.

Primary Spinal Cord Oligodendroglioma with Postoperative Adjuvant Radiotherapy: A Case Report

Primary spinal cord oligodendrogliomas are rare tumors comprising two percent of all spinal cord tumors. Although a treatment guideline has yet to be established, maximal surgical resection is primary in the treatment of spinal cord oligodendrogliomas. Adjuvant radiotherapy has remained controversial, and it is unclear whether chemotherapy adds any benefit. In this case report, the authors present a 24-year-old male who had a seven-year history of left leg weakness and a radiating pain in both legs. Magnetic resonance image (MRI) showed an intramedullary mass at the T4-T8 level. He underwent subtotal removal of the tumor and pathologic diagnosis revealed a WHO grade II oligodendroglioma. The patient was treated with radiotherapy postoperatively and followed up with MRI annually. Clinical and radiological status of the patient had been stationary for four years after the surgery. The five-year follow-up MRI showed an increase in the size and extent of the residual tumor. Despite radiological progression, considering that symptoms and the performance status of the patient had remained unchanged, further treatment has not been performed. Given the clinical outcome of this patient, close observation after subtotal removal with adjuvant radiotherapy is one of the acceptable treatment options for WHO grade II spinal cord oligodendrogliomas.

Methylation of SFRP1 gene promoter in cutaneous squamous cell carcinoma tissue / 中华皮肤科杂志

Objective To investigate the relationship between SFRP1 gene and clinicopathologic features of cutaneous squamous cell carcinoma (CSCC), and to explore the possible mechanism of action of SFRP1 in the occurrence and development of CSCC.Methods CSCC and paracarcinomatous tissue specimens were obtained from 40 patients with CSCC, and normal skin tissue specimens from 40 healthy human controls.The EpiTYPER assay was conducted to evaluate the methylation status of SFRP1 gene promoter in all the specimens with a MassARRAY mass spectrometer.Results Totally, the methylation status of 1951 (86.52％, 1951/2255) CpG motifs were evaluated in 17 CpG loci in 2 fragments of the SFRP1 gene promoter.The methylation rate significantly differed in 10 (10/17, 58.82％) CpG loci between the CSCC and paracarcinomatous tissue specimens, and in 5 (5/17, 29.41％) CpG loci between the paracarcinomatous and normal tissue specimens (all P ＜ 0.05).Furthermore, significant differences were observed in the methylation rates of three CpG loci (CpG 1_5, CpG 1_7, CpG 2_8) in the SFRP1 gene promoter between tissue specimens from different pathological grades of CSCC (P ＜ 0.05), and their methylation rates sequentially decreased from grade Ⅲ to grade Ⅱ and Ⅰ.Conclusion The frequency of methylation is high in the SFRP1 gene promoter in patients with CSCC, and the SFRP1 gene may participate in the occurrence and development of CSCC.

Interaction of polymorphisms in resistin gene promoter -420C/G, cyto-chromes P4501 A1 gene MspI and cigarette smoking on nonalcoholic fatty liver disease / 中国病理生理杂志

AIM:To investigate the interaction of polymorphisms of resistin gene promoter -420C/G, cyto-chromes P4501A1-MspI and cigarette smoking in nonalcoholic fatty liver disease (NAFLD).METHODS: The genetic polymorphisms in resistin gene promoter -420C/G and CYP1A1-MspI were analyzed by the technique of polymerase chain reaction ( PCR) in peripheral blood leukocytes of 900 NAFLD cases and 900 healthy persons.RESULTS:The frequencies of -420C/G (GG) and CYP1A1-MspI (m2/m2) were 49.75%and 50.08%in NAFLD cases and 24.00%and 24.25%in healthy controls, respectively.Statistical tests showed a significant difference in the frequencies between the 2 groups ( P<0.01).The risk of NAFLD with -420C/G (GG) was significantly higher than that of controls.Individuals who carried with CYP1A1-MspI (m2/m2) had a high risk of NAFLD.Combined analysis of the polymorphisms showed that the per-centages of -420C/G (GG)/CYP1A1-MspI (m2/m2) in NAFLD and control groups were 39.83% and 12.83%, re-spectively (P<0.01).The people who carried with -420C/G (GG)/CYP1A1-MspI(m2/m2) had a high risk in NAFLD group.The cigarette smoking rate in NAFLD group was signi-ficantly higher than that in control group ( P<0.01) , and the statistic analysis suggested an interaction between cigarette smoking and -420C/G (GG) and CYP1A1-MspI (m2/m2), which increased the risk of NAFLD.CONCLUSION: -420C/G (GG), CYP1A1-MspI (m2/m2) and cigarette smoking are the risk factors in NAFLD.The interactions between genetic polymorphisms in -420C/G, CYP1A1-MspI ( m2/m2) and cigarette smoking increase the risk of NAFLD.

Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation

OBJECTIVES: Serotonin plays a central role in ejaculation and selective serotonin reuptake inhibitors have been successfully used to treat premature ejaculation. Here, we evaluated the relationship between a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the response of patients with premature ejaculation to SSRI medication. METHODS: Sixty-nine premature ejaculation patients were treated with 20 mg/d paroxetine for three months. The Intravaginal Ejaculatory Latency Time and International Index of Erectile Function scores were compared with baseline values. The patients were scored as having responded to therapy when a 2-fold or greater increase was observed in Intravaginal Ejaculatory Latency Time compared with baseline values after three months. Three genotypes of 5-HTTLPR were studied: LL, LS and SS. The appropriateness of the allele frequencies in 5-HTTLPR were analyzed according to Hardy-Weinberg equilibrium using the χ2-test. RESULTS: The short (S) allele of 5-HTTLPR was significantly more frequent in responders than in nonresponders (p<0.05). Out of the 69 total PE patients, 41 patients (59%) responded to therapy. There was no significant difference in the International Index of Erectile Function score at the end of therapy between the responder and nonresponder groups. The frequencies of the L allele and S allele were 20% and 39%, respectively, in the responder group (p<0.05). CONCLUSION: We conclude that premature ejaculation patients with the SS genotype respond well to selective serotonin reuptake inhibitor therapy. Further studies with large patient groups are necessary to confirm this conclusion. .

Interaction between a serotonin transporter gene promoter region polymorphism and stress predicts anxiety symptoms in adolescents: a multi-wave longitudinal study / 中华行为医学与脑科学杂志

Objective To explore the interaction between a serotonin transporter gene promoter region polymorphism(5-HTTPR) and stress in predicting anxiety symptoms.Methods Through random cluster sampling,a total of 252 healthy adolescents participated in this study.During the initial assessment,all participants completed the Adolescent Life Events Questionnaire (ALEQ) and Multidimensional Anxiety Scale for Children (MASC) to assess their levels of stress and anxiety and were genotyped for the 5-HTTLPR polymorphism.Participants subsequently completed MASC and ALEQ once every three months during the subsequent 24 months.A multilevel model was used to investigate the interaction between 5-HTTLPR and stress that predict anxiety symptoms.Results The results indicated no major effect of 5-HTTLPR in males (β=0.80,P＞0.05)or females(β=-0.21,P＞0.05).There were major effects of stress in males(β=0.30,P＜0.01) and females (β=0.33,P＜0.01)and a significant interaction between 5-HTTLPR and stress.Females with at least one 5-HTTLPR S allele(β=0.11,P＜ 0.01)and males with at least one 5-HTTLPR L allele(β=-0.10,P＜0.01)exhibited more anxiety symptoms under stressful situations.Conclusion The interaction between 5-HTTLPR and stress can predict anxiety symptoms in adolescents.There are gender differences on the 5-HTTLPR × stress interaction.

Difference of Apolipoprotein E promoter polymorphism distribution between Kazak and Han patients with coronary heart disease in Xinjiang / 中国免疫学杂志

Objective:To study the Xinjiang Kazakh,Han nationality patients with coronary heart disease apolipoprotein E gene promoter region rs405509 (G-T),rs449647 (A-T),rs7259620 (G-A) whether there exist differences in the two national distribution between loci polymorphism.Methods:201 cases were studied.DNA product was extracted by using the PheNol-chloroform method and the PCR outcome was purified.We take advantage of multiple single base extension reaction to make DNA Sequencing on The ABI3130XL.Results: The Kazak and Han patients in Xinjiang area in the apolipoprotein E gene promoter rs449647 ( A-T) was statistically significant differences in genotype and allele in two ethnic groups (P0.05).Conclusion:Apolipoprotein E promoter rs449647 ( A-T ) genotype and allele polymorphism have significant differences between Han nationality and Kazak nationality in Xinjiang,others have no statistic difference between the two ethnic groups.

Direct activation of expression vector withβ-casein gene promoter using engineered TALE transcription factors in mouse fibroblasts / 中国实验动物学报

Objective TALE-TFs were adopted to provide a new way in detection of the expression result ofβ-ca-sein gene promoter-interesting gene expression cassettes in mouse fibroblasts.Methods TALE-TFs of eukaryotic expres-sion plasmid and expression cassette withβ-casein gene promoter and red fluorescent protein reporter gene were co-nucleo-fected into mouse fibroblasts by Amaxa nucleofector.Results and Conclusion β-casein gene promoter was activated by artificial TALE-TFs in the mouse fibroblasts.The way is a new expression verification system instead of mammary epithelial cells with fibroblasts.

Essential regulatory elements for NHE3 gene transcription in renal proximal tubule cells

The objectives of the present study were to identify the cis-elements of the promoter absolutely required for the efficient rat NHE3 gene transcription and to locate positive and negative regulatory elements in the 5’-flanking sequence (5’FS), which might modulate the gene expression in proximal tubules, and to compare this result to those reported for intestinal cell lines. We analyzed the promoter activity of different 5’FS segments of the rat NHE3 gene, in the OKP renal proximal tubule cell line by measuring the activity of the reporter gene luciferase. Because the segment spanning the first 157 bp of 5’FS was the most active it was studied in more detail by sequential deletions, point mutations, and gel shift assays. The essential elements for gene transcription are in the region -85 to -33, where we can identify consensual binding sites for Sp1 and EGR-1, which are relevant to NHE3 gene basal transcription. Although a low level of transcription is still possible when the first 25 bp of the 5’FS are used as promoter, efficient transcription only occurs with 44 bp of 5’FS. There are negative regulatory elements in the segments spanning -1196 to -889 and -467 to -152, and positive enhancers between -889 and -479 bp of 5’FS. Transcription factors in the OKP cell nuclear extract efficiently bound to DNA elements of rat NHE3 promoter as demonstrated by gel shift assays, suggesting a high level of similarity between transcription factors of both species, including Sp1 and EGR-1.

Cytokines regulate the promoter activities of human growth hormone gene in rat pituitary MtT/S cells / 中国免疫学杂志

Objective:To study the effect of interleukin-11(IL-11),ciliary neurotropic factor (CNTF) and transforming growth factor-β (TGF-β) on the hGH gene promoter activity in rat pituitary MtT/S cells and the interaction with pituitary-specific transcription factor Pit-1.Methods:Stable transformed MtT/S cell line which contains hGH gene promoter -484-30 bp and luciferase reporter gene firstly established,then the concentration of GH in the medium and lysate of MtT/S cells and luciferase activities in MtT/S cells were measured after treatment these cells with the above cytokines,the effects of cytokines on secretion and synthesis of GH,and the promoter activity of the hGH gene were observed.Results:The results showed that IL-11(20 nmol/L),CNTF(10 nmol/L) and TGF-β(5 nmol/L) regulated secretion and synthesis of GH,and the luciferase expression in stable transformed MtT/S cells.IL-11 and CNTF had the stimulatory effect,whereas TGF-β had the inhibitory effect.Neither overexpression of Pit-1 nor inhibiting Pit-1 expression affected the regulatory role of these cytokines.Conclusion:IL-11,CNTF and TGF-β regulate the GH production in pituitary MtT/S cell line by regulating the hGH gene promoter activity.Pit-1 may not be involved in these actions.

Radiobiology effects of radiation-induced horseradish peroxidase/indole-3-acetic suicide gene expression in lung cancer cells / 中华放射肿瘤学杂志

Objective To detect specific cell killing effect of radiation combined with horseradish peroxidase (HRP)/indole-3-acetic (IAA) suicide gene therapy controlled by a novel radio-inducible and cancer-specific chimeric gene promoter in lung cancer. Methods We constructed a plasmid expressing HRP enzyme under the control of chimeric human telomerase reverse transcriptase (hTERT) promoter carrying 6 CArG elements, a plasmid expressing HRP enzyme under the control of hTERT promoter carrying single CArG element, and two control plasmids, which named pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControl-luc, respectively. After radiation, the proliferation inhibition and apoptosis induction effect of each type of plasmid in lung cancer cells (A549, SPC-A1) and normal lung cells (hEL) was detected by cell counting and Annexin V-FITC staining. The change of radiosensitivity of lung cancer cells with plasmid system was also detected by clonogenic assays. Results After a single dose radiation of 6 Gy,the average proliferation inhibition rates of pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControl-luc systems were 72. 92% ,40.60% , 51.00% and 25.19% (F= 67.31 , P< 0.01) in A549 cells ,64.63%,30.02%,48.23% and 23.16% (F=64.94, P< 0.01) in SPC-A1 cells, and 20.81%,18.05%, 44.20% and 18.32% (F=52. 19,P<0.01) in normal hEL cells, respectively. The average early apoptosis rates of these four plasmid systems were 36. 63%, 22. 30%, 24. 33% and 12. 53% (F =50. 99,P <0. 01) in A549 cells, 33.73%, 17. 37%, 22. 43% and 11.20% (F = 20. 76, P < 0. 01) in SPC-A1 cells, and 13.53 %, 12. 5%, 21.93% and 12. 16% (F = 15. 08, P < 0. 01) in normal hEL cells,respectively. The sensitizing enhancement ratios of the four plasmid systems were 3.45, 2. 29, 3.05 and 1.21 in A549 cells, while 2. 68, 2. 15, 3.05 and 1.21 in SPC-A1 cells, respectively. Conclusions The new suicide gene system controlled by chimeric promoter may provide a novel therapeutic modality for lung cancer.

Methylation Status of the O6-Methylguanine- Deoxyribonucleic Acid Methyltransferase Gene Promoter in World Health Organization Grade III Gliomas

OBJECTIVE: We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter in World Health Organization (WHO) grade III gliomas in association with other molecular markers to evaluate their prevalence. METHODS: The samples of a total of 36 newly WHO grade III glioma patients including 19 anaplastic oligodendrogliomas (AO), 7 anaplastic oligoastrocytomas (AOA), and 10 anaplastic astrocytomas (AA) were analyzed. The methylation status of the MGMT gene promoter was confirmed by methylation-specific polymerase chain reaction. The 1p/19q chromosomal deletion status and EGFR amplification were assessed by Fluorescence In-Situ Hybridization. MGMT, EGFR, EGFRvIII, and p53 expression were analyzed by immunohistochemical staining. RESULTS: The MGMT gene promoter was methylated in 32 (88.9%) and unmethylated in 4 (11.2%). Among them, all of the AO and AOA had methylated MGMT gene promoter without exception. Significant associations between MGMT gene promoter hypermethylation and 1p/19q deletion was observed (p = 0.003). Other molecular markers failed to show significant associations between MGMT gene promoter statuses. CONCLUSION: There was extensive epigenetic silencing of MGMT gene in high grade gliomas with oligodendroglial component. Together with frequent 1p/19q co-deletion in oligodendroglial tumors, this may add plausible explanations supporting the relative favorable prognosis in oligodendroglial tumors compared with pure astrocytic tumors.

Gene Expression of the Micrococcus luteus Fibrinolytic Enzyme (MLFE) in Bacillus subtilis WB600 / 微生物学通报

MLFE (Micrococcus luteus fibrinolytic enzyme) is a fibrinolytic enzyme produced by Micrococcus luteus ML909 strain. The promoter and signal peptide-coding sequence of ?-amylase gene from Bacillus amyloliquefaciens DC-4 was cloned and fused to the sequence coding for mature peptide of MLFE (Gen-Bank: EU232121), forming the fusion gene called amymlfe. This hybrid gene was inserted into the Escherichia coli-Bacillus subtilis shuttle plasmid vector pSUGV4 and expression plasmid pSU-AmyMLFE was constructed. After transformation with B. subtilis WB600, transformant WB600/pSU-AmyMLFE was obtained and produced clear hydrolyzed zones on fibrin plates. The fibrinolytic activity in supernatants of WB600/pSU-AmyMLFE fermented for 24 hours was tested and found to be 238 UKU/mL. The results of SDS-PAGE analysis showed that there was indeed recombinant protein in supernatants. The Western blotting showed that the molecular weight of the expressed protein was the same as expected. These results indicate that the gene, amymlfe, is successfully expressed in B. subtilis WB600.

A pilot study on genetic variation in purine-rich elements in the nephrin gene promoter in type 2 diabetic patients

Diabetic nephropathy (DN) is one of the major complications of type 2 diabetes and is associated with coronary disease. Nephrin, a protein mainly expressed in glomeruli, is decreased in DN and other kidney diseases. Since insulin levels are misregulated in type 2 diabetes, a possible connection between DN and its decreased nephrin expression could be the presence of regulatory elements responsive to insulin in the nephrin gene (NPHS1) promoter region. In this work, using bioinformatic tools, we identified a purine-rich GAGA element in the nephrin gene promoter and conducted a genomic study in search of the presence of polymorphisms in this element and its possible association with DN in type 2 diabetic patients. We amplified and sequenced a 514 bp promoter region of 100 individuals and found no genetic variants in the purine-rich GAGA-box of the nephrin gene promoter between groups of patients with diabetes type 2 with and without renal and coronary complications, control patients without diabetes and healthy controls.

Gene Expression Analysis of a Late Embryogenesis Abundant Gene from Salvia miltiorrhiza Bunge / 中国生物工程杂志

According to the sequence of SmLEA gene,a DNA fragment of 1 038 bp upstream of the coding sequence of SmLEA gene was amplified by DNA walking with the genomic DNA of Salvia miltiorrhiz as the template.Sequence analysis showed that the fragment contained some putative cis-elements relating to abiotic stress,ABA,seed specific expression.So the S.miltiorrhiz seedings was treated with 100?mol/L ABA,200mmol/L NaCl,4℃,and subjected to dehydration.The real-time PCR showed that expression levels of SmLEA was increased obviously,which was in accordance with the sequence analysis.

Correlation between the Promoter Polymorphism of Fibroblast Growth Factor 1 gene and Late-onset Alzheimer's Disease / 中国康复理论与实践

@#ObjectiveTo evaluate the correlation between the promoter polymorphism of Fibroblast Growth Factor 1 (FGF-1) and late-onset Alzheimer's disease (LOAD). MethodsClinic pathological data from 206 autopsies were analyzed, including 100 autopsy-confirmed LOAD patients and 106 age-matched non-demented controls. PCR-RFLP (Restriction fragment length polymorphism) approach was used to determine the genotype of the promoter polymorphism of FGF-1 gene. ResultsThe genotyping frequencies of the promoter polymorphism (-1385 A/G) were AA 20 (10%), GA 89 (43%), GG 97 (47%), respectively. There was significant (P=0.027) difference of genotyping frequencies between the cases and controls; GG genotype was positively associated with LOAD (odds ratio=2.02, 95%CI:1.16～3.52). ConclusionThe promoter polymorphism (-1385 A/G) of FGF-1 gene was associated with LOAD.

In vivo study on the effect of adenovirus mediating Smad 7 gene expression regulated by radiation via Egr-1 promoter in C57BL mice implanted with Lewis lung cancer / 中华放射肿瘤学杂志

Objective Objective To study the effect of adenovirus mediating Smad 7 gene regulated by radiation via Egr-1 on the primary tumor and lung metastasis in C57BL mice implanted with Lewis lung cancer.Methods The radio-inducible elements from the Egr-1 gene promoter were inserted upstream to a cDNA encoding Smad7 and integrated into a replication-defective adenovirus to generate recombinant adenovirus(AD.Egr-Smad 7).270 mice implanted with Lewis lung cancer in the hind legs were used and the experiment was started when the transplanted tumor diameter reached 0.8 to 1.0cm.Then three investigations were undertaken,each demanding 90 mice implanted with Lewis lung cancer respectively.To each group,90 mice models were randomized into 3 groups: the normal control group;the NS control group;and the implanted AD.Egr-Smad 7 group.Every 6 mice in each group were irradiated by different single dose to study the following: 1.The maximal and minimal diameters of the tumor were recorded to observe the tumor growth tendency,the tumor growth delay and the mice survival time,2.The incidence of lung metastasis two weeks after the radiation was recorded.3.The incidence of lung metastasis when the tumor volume was four times as large as that at the beginning of radiation was recorded.Results The adenovirus mediating Smad 7 gene expression regulated by irradiation via Egr-1 in C57BL mice implanted with Lewis lung cancer was able to inhibit the progression of the primary tumor and prolong the survival of the mice significantly as compared with the control group(P0.05).Conclusions The gene expression of AD.Egr-Smad 7 regulated by radiation is not risky in promoting the local progression and distant metastasis of Lewis lung cancer in mice.On the other hand,the gene expression of AD.Egr-Smad 7 regulated by radiation could inhibit the progression of the primary tumor and prolong the survival time of the mice significantly.It is safe,to some extent,of using AD.Egr-Smad 7 to block the signal transduction of TGF-?locally as a novel strategy for gene therapy aiming at the prevention of radiation-induced lung

No Association Between the 5-HT 2A Receptor Gene Promoter Polymorphism(-1438A/G) and Schizophrenia in a Korean Population / 신경정신의학

OBJECTIVES: This study was designed to investigate the association between 5-HT 2A receptor gene promoter -1438A/G polymorphism and schizophrenia in a Korean population. METHOD: 5-HT 2A receptor gene promoter -1438A/G polymorphism was typed with Polymerase Chain Reaction in 132 patients with schizophrenia and 138 healthy normal controls. RESULT: There was no difference in allelic frequency of -1438A/G polymorphism between patients with schizophrenia and controls(K 2=2.261, df=1, p=0.133). A difference was found in genotype distribution(K 2=6.157, df=2, p=0.046), but this difference was being given by the increased A/A in th controls and A/G in the patients. The genotype frequency, which is the sum of homozygosity and heterozygosity for the -1438 G allele, was significantly higher in the patients(K 2=5.880, df=1, p=0.015). However, there was no difference between the patients with schizophrenia and conrols in the frequency of homozygosity for the -1438 G allele. CONCLULSION: These results suggest that -1438A/G polymorphism of the 5-HT 2A receptor gene promoter is not causally related to the development of schizophrenia in a Korean population.