Modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-hydroxypyrene excretions / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-hydroxypyrene (1-OHP) excretions in workers under different exposure levels.</p><p><b>METHODS</b>Four hundred and forty-seven occupationally exposed workers from two coking plants and 220 control workers from a wire rod plant were genotyped to analyze the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-OHP excretions.</p><p><b>RESULTS</b>The urinary 1-OHP concentration in exposed group was much higher than that in control group (4.61 vs 0.34 µmol/mol Cr, P < 0.05). Occupational exposure levels and cigarette smoking were of the dominating factors affecting 1-OHP excretions in urine. After controlling potential confounders, decreased excretion of urinary 1-OHP was associated with GSTP1 I105V AG + GG genotype in coke oven workers (single-gene model, P = 0.012; multi-gene model, P = 0.011) and with GSTT1 null type in the analysis including all subjects (P = 0.055 in both single-gene and multi-gene models). GSTT1 and GSTP1 were interacted on the urinary concentrations of 1-OHP.</p><p><b>CONCLUSION</b>Urinary 1-OHP concentrations can be modified by GSTM1, GSTT1 and GSTP1 gene polymorphisms, indicating that these genes are involved in the metabolism of polycyclic aromatic hydrocarbons.</p>

Establishment of a multiplex ligation-dependent SNP genotyping method and its application in the detection of genes related to chemotherapeutic drugs in breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To establish a method for SNP genotyping of multi-genes by allele-specific oligonucleotide probe ligation mediated by a thermostable ligase, and to explore the genetic polymorphisms of drug-metabolizing enzymes in breast cancer patients and their association with chemotherapeutic responses.</p><p><b>METHODS</b>10 SNP loci of enzyme genes related to chemotherapeutic drugs such as taxanes, anthracyclines and cyclophosphamide were selected, and were genotyped for blood samples from 126 breast cancer patients by the established method. Their correlations with therapeutic responses were retrospectively evaluated.</p><p><b>RESULTS</b>The lower detection limit of genomic DNA by this developed method was 6.25 ng. The fluorescent peak locations of ligation products on ABI PRISM 377 DNA sequencer were accurate and consistent with prospective sizes in bases (Bias range 0.08 - 0.69 bp, x(-) = 0.31 bp, s = 0.18 bp). Same genotyping results were obtained for repeat tests of 8 random samples, which were further confirmed by sequencing analysis. The 10 SNP loci were polymorphic of different frequency in the breast cancer patients. The combinations with GSTP1 genotypes and GSTM1 genotypes were related to anthracycline-based chemotherapy efficacy (P = 0.037), and the low GSTs activity group (GSTP1 variant allele + GSTM1 null) showed the best effects (85.7%). GSTM1 genotypes and their combinations with GSTP1 and/or CYP3A5*3 genotypes were related to taxane-based therapy efficacy (P < 0.05 for all), and both the low GSTs activity group and the drug slow-metabolising group (low GSTs activity group + CYP3A5*3 wild allele) showed better effects (100%).</p><p><b>CONCLUSION</b>The established method is reliable and applicable in multiplex SNPs genotyping of multi-genes. SNPs combination may have a better clinical application value for prediction of chemotherapeutic responses.</p>

Clinical observation on treatment of hyperplasia of mammary gland by Lirukang Granule / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the efficacy and mechanism of Lirukang Granule in treating hyperplasia of mammary gland (HMG).</p><p><b>METHODS</b>One hundred patients with HMG were randomly assigned to two groups, 50 in each group. The patients in the treated group were orally administered with LRKG thrice a day, one package each time, and those in the control group were given orally Rukuaixiao Tablet thrice a day, 4 tablets each time. The therapeutic course for both groups was 4 months. The clinical efficacy, pain alleviating rate, as well as changes of local sign and symptom scores were observed before and after treatment. The changes of serum estradiol (E(2)), progesterone (P), testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) in some randomly selected patients (24 patients in the treated group and 24 in the control group) before and after treatment were measured with radioimmunoassay.</p><p><b>RESULTS</b>The total clinical efficacy in the treated group was superior to that in the control group, significant difference was shown between the two groups (P < 0.01). The cure-effective rate and total effective rate in the treated group were 70.0% and 88.0% respectively, significantly higher than those in the control group (38.0% and 64.0%) respectively (P < 0.01), and the pain alleviating rate in the treated group was also significantly higher in the former than that in the latter (88.0% vs 64.0%, P < 0.05). Moreover, the treated group showed obvious superiority in improving the patients' symptom and sign scores (P < 0.01), and abnormalities of gonadal hormone as compared with the respective items in the control group (P < 0.01).</p><p><b>CONCLUSION</b>LRKG has good efficacy in the treatment of HMG, and its mechanism may be related to the regulation on endocrine and immune function.</p>

Effects of chemotherapy on circulating angiogenic factor levels in patients with breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the changes in circulating VEGF and endostatin (ES) levels during chemotherapy for patients with breast cancer, and their correlation with efficacy of chemotherapy.</p><p><b>METHODS</b>40 breast cancer patients with metastases were included in this study. They received TAC/TEC, CAF/CEF, NP, CAP, CMF, TFP, TA or TC regime chemotherapy, respectively. Totally 120 serum samples were collected from the patients at three time points: before chemotherapy, the end of 1 and 5-6 chemotherapy cycles, and analyzed for VEGF and ES levels using ELISA. Tumor agiogenesis activity was evaluated by serum soluble vascular cell adhesion molecule (VCAM - 1) measured by ELISA as a surrogate marker.</p><p><b>RESULTS</b>(1) Before chemotherapy, the median level of VEGF in patients with breast cancer was 496.6 pg/ml, 4.7 times higher than that of healthy controls (P <0.001). The median level of ES was 95.5 ng/ml, 18.3% lower than that of healthy controls (P = 0.183). VCAM-1 was 1077.1 ng/ml and higher than that of controls (P <0.001). The serum VEGF levels correlated with VCAM-1 levels, tumor staging and metastatic sites (P <0.05). (2) At the end of 1 cycle of chemotherapy, the serum VEGF level (median 524.8 pg/ml) was higher than the pretreatment values (P = 0.047), whereas the levels of ES and VCAM-1 were not significantly altered (110.5 ng/ml, P = 0.055; and 975.6 ng/ml, P = 0.27). (3) At the end of 5-6 cycles, the changes in VEGF correlated with the response to chemotherapy. Serum VEGF levels in 27 patients with chemotherapy-responsive and stable disease showed a significant decrease (median 287.4 pg/ml) , but not observed in 13 patients with progressive disease. VCAM-1 also showed a treatment-related change like VEGF. However, chemotherapy might only have a minor effect on ES, because there was no significant difference in the ES levels among 5-6 cycle patients, 1 cycle patients and healthy controls, and neither between therapy-responsive patients.</p><p><b>CONCLUSION</b>Intensive chemotherapy for breast cancer results in a significant decrease of serum VEGF level, which might be an indicator of the controlled disease status, and following the treatment-induced response or stabilization, the tumor angiogenesis seems to change into an anti-angiogenesis direction.</p>