Progress of circulating tumor DNA in cervical cancer / 肿瘤研究与临床

Cervical cancer is a leading cause of cancer death in women. There are no reliable noninvasive indicators to predict the recurrence, metastasis and prognosis of cervical cancer. Circulating tumor DNA (ctDNA) is a kind of DNA fragment released from tumor cells into the blood circulation, which has the advantages of being non-invasive, real-time, and of reflecting the genetic characteristics of tumors. With the improvement of ctDNA detection technology and in-depth research on ctDNA, ctDNA has shown more obvious advantages in early diagnosis, tumor molecular typing, treatment monitoring and recurrence prediction of cervical cancer compared with traditional histological, serological and imaging detection methods. This paper reviews the detection methods of ctDNA and its latest research progress of ctDNA in cervical cancer.

A case of giant ovarian goiter, pleural effusion and peritoneal effusion with marked elevation of glycoantigen 125 / 中国综合临床

The incidence of struma ovarii(SO) is low, accounting for 5% to 15% of ovarian teratoma.Huge SO, pleural effusion and ascites with elevated carbohydrate antigen 125 are rare.There is no perfect clinical treatment guideline for the diagnosis and treatment of SO.MRI of patients with SO showed " Black Pearl" appearance.Appendectomy can be selected as the operation method.Postoperative pathology can confirm the diagnosis, and the prognosis is good.

Progress of correlation between clinical hematologic parameters and prognosis of cervical cancer / 肿瘤研究与临床

Clinical hematologic parameters refer to the reference data of blood tests such as routine blood and blood biochemistry. Inflammatory cells and inflammatory mediators are important components of the tumor microenvironment and play an important role in the process of tumor occurrence and development. This article reviews that clinical hematologic parameters have special clinical reference significance for cervical cancer invasion and metastasis, radiotherapy response and prognosis evaluation through analysis of clinical hematologic parameters and cervical cancer prognosis studies, such as the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

Changes of the expression for genes related with senescence and the telomerase activity during cellular replicative and premature senescence in human embryonic lung fibroblasts / 中华劳动卫生职业病杂志

Objective@#To detect the alterations of telomerase activity and the expression for oxidative stress responsive genes related with senescence during cellular replicative senescence and hydrogen peroxide-induced premature senescence in human embryonic lung fibroblasts (HELFs) in vitro.@*Methods@#The HELFs were divided into young cells (22 population doubling levels, 22PDL) , mid-aged cells (35PDL) and replicative senes-cent cells (49PDL) and premature senescent cells induced by H2O2(premature senescence, PS). The telomerase activity was detected by ELISA assay during cellular replicative and premature senescence. The mRNA level of oxidative stress responsive genes related with senescence for Foxo1, Foxo3, Pdx1, apoA-I and MMP1 was per-formed by RT-Q-PCR separately.@*Results@#The mRNA level for Foxo1, Foxo3, apoA-I and Pdx1 was decreased separately during cellular replicative senescence compared to that in the young-stage cells with statistical signifi-cance (P<0.05). The expression of MMP1 was up-regulated 5.1-fold obviously (P<0.05). In premature senes-cence, the mRNA level was only decreased for Foxo1, Foxo3 and apoA-I, but up-regulated 2.3-fold and 6.2-fold for Pdx1 and MMP1 respcetively vs 22PDL significantly (P<0.05). The telomerase activity in young cells was not detected, and it increased in mid-aged cells and replicative senescence stages during cellular replicative se-nescence as compared to 22PDL with statistical significance (P<0.05). The telomerase activity in premature se-nescence was highly active.@*Conclusion@#The expression for genes related with senescence has differences be-tween replicative and premature senescence and hydrogen peroxide modifies their expression levels. The telomer-ase activity has been going up with increased PDLs.

Effect of bisphenol A on differentiation potential of mouse embryonic stem cells / 中国药理学与毒理学杂志

OBJECTIVE To explore the effect of bisphenol A (BPA) on the differentiation potential of embryonic stem cells, and provide an experimental basis for evaluation of safety of BPA. METHODS Mouse embryonic fibroblasts (MEFs) and embryonic stem cells (ESCs) were treated with BPA 0.1, 1, 10, 100 and 1000 μmol.L-1 for 8 d respectively. The viability of MEFs and ESCs was measured by CCK-8 and lC50 was calculated. The mRNA expression of α-myosin heavy chain in ESCs was tested by RT-PCR to determine lD50 . The embryonic body cultured by suspension method was treated with BPA 0.001, 0.01, 0.1 and 1 μmol.L-1 for 10 d respectively. The changes of marked genes in each blastoderm were detected by RT-PCR. RESULTS lC50 of BPA to mouse ESCs was 5.22×10-4 mol.L-1 , and to MEFs was 6. 25 × 10-4 mol.L-1 . lD50 of BPA to mouse ESCs differentiating to cardiomyocytes was 7.0×10-7 mol.L-1 . BPA 0.001 and 0.01 μmol.L-1 upregulated the expression of the marked genes of mesoderm, fetal liver kinase-1 and globin transcription factor 1. CONCLUSION BPA is a strong embry-otoxic compound. BPA of low concentration can promote the differentiation of mouse ESCs to mesoderm.

Hedgehog signaling pathway in chemocarcinogenesis and progression of breast cancer / 中国药理学与毒理学杂志

The controversial results of several studies suggest that certain everyday-use chemicals may be linked to breast cancer. ln recent years, extensive researches have been carried out to under-stand breast carcinogenesis and the hedgehog(Hh) signaling pathway has emerged as a critical determi-nant of human breast cancer. Aberrant Hh signaling in adults results in carcinogenesis, angiogenesis, and metastasis. This review is focused on the Hh signaling pathway and chemicals in the regulation of breast cancer development and provide an updated survey of pre-clinical and clinical trials of novel strategies to target them.

Effect of silicon dioxide nanoparticles on expression and DNA methylation of PARP-1 gene in HaCaT cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effect of silicon dioxide nanoparticles on the expression and promoter region CpG islands methylation of (Poly [ADP-ribose] polymerase 1, PARP-1) gene in human HaCaT Cell.</p><p><b>METHODS</b>HaCaT Cells were treated with nm-SiO₂at 0, 2.5, 5 and 10 µg/mL and micro-SiO₂at 10 µg/ml for 24 h and DAC treatment was given at 10 µg/ml group for 48 h. Real-time PCR and western blot assay was used to detect the expression of PARP-1 mRNA and protein. BSP (Bisulfite Pyrosequence, BSP) assay was used to detect the promoter region CpG islands methylation status of PARP-1 gene.</p><p><b>RESULTS</b>After exposure to nano-SiO₂particles, compared to CTRL group, the mRNA and protein expression of PARP-1 in micro-SiO₂and 2.5 µg/ml group unchanged, but he mRNA and protein expression of PARP-1 in 5, 10 µg/ml as well as DAC group was down-regulated and there are statistical significance between CTRL group and 5, 10 µg/ml as well as DAC group and the PARP-1 promoter region CpG islands showed methylation.</p><p><b>CONCLUSION</b>nano-SiO₂can down-regulate PARP-1 expression in HaCaT Cell and this is associated with the change in the methylation of PARP-1 gene promoter region CpG islands induced by nano-SiO₂particles.</p>

Effect of poly-ADP-ribosylation on the alteration of DNA methylation level of human bronchial epithelial cells induced by Cr (VI) / 中华预防医学杂志

<p><b>OBJECTIVE</b>To reveal the role of poly-ADP-ribosylation and DNA methylation in carcinogenic process induced induced by Cr (VI), and to discuss the relations between them.</p><p><b>METHODS</b>The pre-established Poly (ADP-ribose) glycohydrolase (PARG) deficient cells and 16HBE cells were treated with different concentrations of Cr (VI), and the changes of total genomic DNA methylation level in different groups were detected by methylation immunofluorescent detection, as well as the changes of the activity of methyltransferases. Moreover, RT-PCR and western blotting method were applied to analyze the changes of expression of DNMT1, DNMT3a, DNMT3b and MBD2, upon the protein level.</p><p><b>RESULTS</b>After treated by Cr(VI) for 24 h, the healthy 16HBE cells showed a significant lower level of genomic DNA methylation; however, there was no significant changes (P > 0.05) found in PARG deficient cells by immunofluorescence assay. When the dose of Cr (VI) reached 5.0 µmol/L, the activity of methyltransferases in 16HBE cells and PARG deficient cells (49.33 ± 2.65, 80.05 ± 2.05) decreased by 20% and 50% comparing with contrast group (99.27 ± 1.10, 99.30 ± 0.60) . After treated by Cr (VI) for 24 h, the expression of mRNA and protein level among DNMT1, DNMT3a, DNMT3b and MBD2 decreased significantly in healthy 16HBE cells; and the expression of DNMT1 and DNMT3a decreased in PARG deficiency cells. The relevant expression levels of mRNA of DNMT1 were separately (0.99 ± 0.09), (0.79 ± 0.10), (0.59 ± 0.13) and (0.39 ± 0.02) (F = 247.17, P < 0.01), the expression levels of protein were separately (1.00 ± 0.03), (0.69 ± 0.15), (0.65 ± 0.10) and (0.55 ± 0.13) (F = 214.12, P < 0.01), the expression levels of DNMT3a mRNA were separately (1.00 ± 0.04) , (0.93 ± 0.11) , (0.79 ± 0.07) , (0.59 ± 0.05) (F = 498.16, P < 0.01) , and the expression levels of protein were separately (1.00 ± 0.14) , (0.97 ± 0.11) , (0.79 ± 0.17) , (0.57 ± 0.15) (F = 390.11, P < 0.01) when the dose of Cr (VI) at 0, 0.3, 1.2 and 5.0 µmol/L. However, there were no significant changes of expression found in DNMT3b and MBD2.</p><p><b>CONCLUSION</b>Poly-ADP-ribosylation could regulate the activity of DNMT3b and MBD2, protect cells against the DNA methylation alteration induced by Cr(VI) and maintain the global genomic DNA methylation level.</p>

Human GSTs polymorphisms in the Hakka population of south China and their associations with family history of several chronic diseases / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the associations of genetic polymorphisms in GSTs genes of the Hakka population of south China with family histories of certain chronic diseases.</p><p><b>METHODS</b>Five hundred and thirty-nine healthy Hakka natives of Meizhou city of Guangdong province in south China were involved. The genotypes of GSTM1, GSTT1, GSTP1, GSTM3, and GSTA1 were determined using PCR and restriction fragment length polymorphism analysis. The observed polymorphisms were analyzed by Chi-square and Hardy-Weinberg equilibrium tests. Logistic regression analysis was used to determine the associations of the distributions of GST genotypes with family history of certain chronic diseases.</p><p><b>RESULTS</b>The distributions of polymorphisms in GSTP1, GSTM3, and GSTA1 conformed to the Hardy-Weinberg equilibrium. Compared to the Cantonese, the Hakka had a lower distribution of the GSTM3 deletion genotype (3.15% vs. 11.9%). A weak association was observed between the GSTM1 genetic polymorphism and family history of hypertension. Alcohol drinkers had a higher frequency of the null-GSTM1 genotype, while smokers had a higher frequency of a variant GSTP1 genotype.</p><p><b>CONCLUSION</b>The results suggest that the Hakka is a special and distinctive Han Chinese ethnic group with different GSTs genetic polymorphisms. Smoking and drinking might be related to the distribution of GST genotypes.</p>

Epigenetic Modifications of PI6 during Cellular Senescence / 环境与健康杂志

Objective To understand the epigenetic regulations of P16 during cellular replicative senescence and premature senescence induced by hydrogen peroxide of human embryonic lung fibroblasts(HEFs).Methods The normal HEFs were divided into young cells(22 PDL),mid-aged cells(35 PDL)and replicative senescent cells(49 PDL)during replicative senescence.The synchronously cultured 22 PDL HEFs were exposed for 2 h to 400?mol/L H_2O_2 at half confluence on daily basis.The procedure lasted for 4 consecutive days.And then the treated cells were cultured for another 7 days,called premature senescent cells.The mRNA level of P16 was detected by fluorescence quantitative PCR.The methylation level in the promoter region -846～-639 bp was observed by methylation-specific PCR(MSP).The histone modifications was detected by chromatin immunoprecipitation-QPCR assay,including acetylation for H3,H4 and methylation for H3(Lys4)and H4(Lys20).Results In the process of cellular senescence,the mRNA level of P16 decreased in mid-aged cells,but increased significantly in both replicative and premature senescent cells compared with that of young cells(P

Distribution of Polymorphisms and Linkage of GSTM1 and GSTM3 Genes in Healthy Cantonese in Southern China / 环境与健康杂志

Objective To determine the prevalence of the polymorphisms of GSTM1 and GSTM3 genes in target population in Guangdong province and to investigate the linkage between the two genes and their association with the family history distribution of the target population. Methods Polymerase chain reaction-restriction (PCR)-2% agarose gel electrophoresis and PCR-12% PAGE electrophoresis approaches were employed to detect the genotype of the GSTM1 and GSTM3. The data was analyzed with SPSS10.0 software. Results The frequency of GSTM1(-) genotype was 56.8%(n=597). The frequency of genotype of GSTM3*A-*A,*A-*B,*B-*B were 62.3%,25.8%,11.9% respectively. Conclusion A linkage between the GSTM1 and GSTM3 gene is showed in the present paper. The analysis of logistic regression shows that the expression of homozygote for GSTM3*B-*B gene is correlated with the family history of coronary heart disease in the target population.