1.Quantitative analysis of LMX1A and PAX1 gene methylation in cervical cancer and cervical intraepithelial neoplasia
Wei CHEN ; Huijuan YANG ; Jun XU ; Haoping ZHU
China Oncology 2015;(1):19-24
Background and purpose:DNA methylation is a common epigenetic alteration in cervical carcino-genesis. The aim of this study was to measure the levels of LMX1A and PAX1 gene methylation in cervical cancer and pre-cursors and to identify their potential in clinical application. Methods:Cervical specimens were collected from 121 female patients including 27 cases with invasive cervical cancers (ICC), 34 cases with high-grade cervical intraepithelial neoplasia (HG-CIN), 32 cases with low-grade cervical intraepithelial neoplasia (LG-CIN) and 28 cases with chronic cervicitis as normal controls (NLM). DNA methylations of the LMX1A and PAX1 gene were quantified using the techniques of nest PCR and pyrosequencing. The mean methylation values of the 6 gene loci on the LMX1A gene and the 9 gene loci on the PAX1 gene were respectively calculated for a given sample. Receiver operating characteristic (ROC) curve was used to evaluate the accuracy of gene methylation analysis to discriminate the cervical diseases. Results:The mean methylation value of the LMX1A gene in ICC was 14.36%, which was significantly higher than those in HG-CIN (4.70%), LG-CIN (5.05%) and NLM (4.53%) (P<0.01). The mean methylation value of the PAX1 gene in ICC was 41.97%, which was significantly higher than those in HG-CIN (10.21%), LG-CIN (5.55%) and NLM (4.92%) (P<0.01). The area under the ROC curve (AUC) was 0.603 for LMX1A gene methylation, and was 0.883 for PAX1 gene methylation, to discriminate ICC from HG-CIN, LG-CIN, and NLM (P=0.104 and<0.001, respectively). The optimal cut-off value for PAX1 gene methylation was set at 20.50%with the sensitivity of 81%and with the specificity of 93%. If the cut-off value was set at 9.58%, the sensitivity and the specificity of PAX1 gene methylation were 89%and 84%respectively. Conclusion:Quantitative analysis of the PAX1 gene methylation in cervical tissue might be helpful to differentiate invasive cancers from precursors, while the clinical applica-tion of the LMX1A gene methylation was limited.
2.Interventions of pregnancies with borderline gestational glucose intolerance: a randomized controlled trial
Zheng HU ; Haoping ZHU ; Jun XU ; Linan CHENG
Chinese Journal of General Practitioners 2013;(5):370-373
Objective To explore the effectiveness of dietary treatment in reducing macrosomia risks for pregnancies with borderline gestational glucose intolerance (BGGI).Methods From July 2009 to June 2011,a total of 1046 pregnant women with BGGI were randomized into group A (intervention,n =525) and group B (non-intervention,n =521).Another 521 pregnancies with normal glucose screening were assigned into group C (normal control).Randomization was applied following stratification according to age,body mass index (BMI),prior Cesarean section (C-section) and multiparity,etc.Women in group A underwent the examinations of fasting plasma glucose (FPG),2 h-post prandial glucose and HbA1c once every 2 weeks.Their newborn outcomes were collected for analysis.Results Women of three groups were similar in age,parity,initial BMI and initial FPG.Dietary treatment for group A improved glucose-related indices and women's pregnancy weight gain (P <0.0l).Also,in comparison with group B,the intervention of group A reduced risk of macrosomia (9.14% vs.13.82%,P =0.02),prior C-section rate (43.87% vs.56.07%,P < 0.01) and postpartum hemorrhage (3.81% vs.7.10%,P =0.02).However these indices were no better than group C.Dietary treatment did not increase the risk of fetal growth restriction,neonatal hypoglycemia and hyperbilirubinemia.Conclusion As a simple noninvasive therapeutic measure for improved glucose tolerance,BGGI may reduce the risk of risk of macrosomia and prior C-section rate.
3.Clinical significance of diffusely increased 18F-FDG uptake in the thyroid
Ge ZHAI ; Biao LI ; Miao ZHANG ; Haoping XU ; Chao WANG ; Guizhi GE ; Chenwei SUN ; Chenmo ZHU
Chinese Journal of Endocrinology and Metabolism 2009;25(4):418-419
lymphocytic thyroiditis.
4.A Novel In Situ Gel Formulation of Ranitidine for Oral Sustained Delivery.
Haoping XU ; Min SHI ; Ying LIU ; Jinling JIANG ; Tao MA
Biomolecules & Therapeutics 2014;22(2):161-165
The main purpose of this study was to develop a novel, in situ gel system for sustained delivery of ranitidine hydrochloride. Ranitidine in situ gels at 0.2%, 0.5%, and 1.0% gellan gum concentration (w/v) were prepared, respectively, and characterized in terms of preparation, viscosity and in vitro release. The viscosity of the gellan gum formulations in solution increased with increasing concentrations of gellan gum. In vitro study showed that the release of ranitidine from these gels was characterized by an initial phase of high release (burst effect) and translated to the second phase of moderate release. Single photon emission computing tomography technique was used to evaluate the stomach residence time of gel containing 99mTc tracer. The animal experiment suggested in situ gel had feasibility of forming gels in stomach and sustained the ranitidine release from the gels over the period of at least 8 h. In conclusion, the in situ gel system is a promising approach for the oral delivery of ranitidine for the therapeutic effects improvement.
Animal Experimentation
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Ranitidine*
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5.Gene-targeted radiation therapy mediated by radiation-sensitive promoter in lung adenocarcinoma and the feasibility of micro-PET/CT in evaluation of therapeutic effectiveness in small animals.
Haoping XU ; Rui GUO ; Yening JIN ; Biao LI
Chinese Journal of Oncology 2014;36(5):329-334
OBJECTIVETo explore the combined anti-tumor effect of radiation therapy and gene-targeted suppression of tumor neovasculature in lung adenocarcinoma in vivo, and to explore the feasibility of micro-PET/CT in dynamic evaluation of treatment effectiveness.
METHODSThirty 5-6-week old male BALB/c nude mice were used in this study. The mouse models of xenotransplanted human lung adenocarcinoma were divided into 5 groups at random, six mice in each group: the control group, radiation treatment alone group and three groups of recombinant baculovirus plus radiation treatment (intratumoral injection, tail vein injection, and intramuscular injection). The tumor volume was measured every 2 days. Growth delay time (GD) and growth inhibition rate was calculated. FDG metabolism was evaluated by micro-PET-CT before and after treatment. The expressions of VEGF, CD31 and Ki-67 were detected by immunohistochemistry (IHC).
RESULTSThe tumor growth delay was >12 days, and the tumor inhibition rate was >45% in the recombinant baculovirus combined with radiotherapy groups, significantly higher than that of the radiotherapy alone group (P < 0.05). Immunohistochemical analysis showed that the expressions of VEGF, CD31 and Ki-67 were significantly lower than that in other groups (P < 0.05). The micro-PET-CT assessment showed that the FDG-metabolism in the recombinant baculovirus combined with radiotherapy groups was significantly reduced (P < 0.05), and the SUVmax (FDG metabolism) of transplanted tumors after treatment was also markedly decreased in comparison with that of the control group. The tumor volume after treatment was significantly correlated with SUVmax in the recombinant baculovirus intratumoral injection + radiotherapy group(r = 0.976), recombinant baculovirus intravenous injection + radiotherapy group (r = 0.954), recombinant baculovirus intramuscular injection + radiotherapy group (r = 0.929), and radiotherapy alone group (r = 0.871, P < 0.05).
CONCLUSIONSThe recombinant baculovirus containing Egr1 promoter and K5 gene combined with radiotherapy enhances the suppressing effect on the growth of lung adenocarcinoma in the tumor-bearing nude mice. The inducibility of Egr1 promoter by radiation allows the targeting and controllability of treatment. Micro-PET-CT results have a good correlation with the treatment effectiveness. Therefore, it can be used in real-time evaluation of tumor metabolic function in vivo.
Adenocarcinoma ; metabolism ; pathology ; radiotherapy ; Animals ; Baculoviridae ; genetics ; Cell Line, Tumor ; Combined Modality Therapy ; Early Growth Response Protein 1 ; genetics ; physiology ; Fluorodeoxyglucose F18 ; Genetic Therapy ; Genetic Vectors ; Humans ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; radiotherapy ; Male ; Mice, Inbred BALB C ; Mice, Nude ; Molecular Targeted Therapy ; Neoplasm Transplantation ; Peptide Fragments ; genetics ; physiology ; Plasminogen ; genetics ; physiology ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Positron-Emission Tomography ; Promoter Regions, Genetic ; Random Allocation ; Recombinant Proteins ; genetics ; Tomography, X-Ray Computed ; Tumor Burden ; Vascular Endothelial Growth Factor A ; metabolism