Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial / 医学前沿

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

Efficacy and impact of PARPi monotherapy to subsequent platinum-based chemotherapy in BRCA1/2 mutant ovarian cancer patients with secondary platinum-sensitive relapse / 부인종양

Objective@#The therapeutic effect of poly(ADP-ribose) polymerase inhibitors (PARPi) monotherapy compared with platinum-based chemotherapy, and the impact to subsequent platinum-based chemotherapy after PARPi resistance were inconclusive. @*Methods@#BRCA1/2 mutant ovarian cancer patients with secondary platinum-sensitive relapse were included. The patients did not receive any maintenance regimen after first- and second-line platinum therapy, and the secondary platinum-free interval (PFI) was more than 6 months. Patients in study group were treated with PARPi monotherapy until disease progression, and patients in control group were treated with platinum-based chemotherapy. @*Results@#A total of 64 patients were retrospectively analyzed, including 31 (48.4%) in study group and 33 (51.6%) in control group. The objective response rate (77.4% vs. 84.0%; p=0.538) and median progression-free survival (8.6 vs. 11.1 months; p=0.679) were comparable. PARPi monotherapy significantly prolonged post-recurrent survival (PRS) (hazard ratio [HR]=0.35; p=0.024), and was the independent factor associated with PRS (HR=0.33; p=0.038) in multivariate analysis. The median time from treatment to first subsequent therapy or death (mTFST) of patients with platinum-based chemotherapy after PARPi progression and patients in control group with PFI ≥6 months after third-line platinum-based chemotherapy was comparable (mTFST: 7.5 vs. 7.1 months; p=0.800). Further survival analysis showed that PRS of patients with PARPi monotherapy were similar to patients with PFI ≥6 months after third-line platinum chemotherapy (HR=0.66; p=0.503), and superior to patients with PFI <6 months after third-line platinum chemotherapy (HR=0.15; p=0.009). @*Conclusion@#PARPi monotherapy was equivalent to platinum-based chemotherapy for BRCA1/2-mutated ovarian cancer patients with secondary platinum-sensitive recurrence, and could improve prognosis.

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial / 医学前沿

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

Clinical features and prognosis of cervical adenocarcinoma and adenosquamous carcinoma: an analysis of 237 cases / 浙江大学学报·医学版

OBJECTIVE@#To analyze the clinical features and prognosis of cervical adenocarcinoma (AC) and adenosquamous carcinoma of cervix (ASC).@*METHODS@#The clinical data of 237 patients, including 201 cases of AC and 36 cases of ASC (FIGO stage ⅠB1-ⅡA), who underwent surgery in Qilu Hospital between September 2007 and September 2016 were reviewed. Clinical features of two groups were compared, and Kaplan-Meier survival analysis was performed to evaluate the prognosis.@*RESULTS@#A larger proportion of ASC patients had lymphovascular space invasion compared with AC patients (0.05). The 5-year overall survival rates of AC and ASC groups were 79.4% and 78.3%, and the 5-year recurrence-free survival rates were 77.4% and 73.0%. Among patients received concurrent chemoradiotherapy, the 5-year overall survival rates were 71.0% and 61.4%, and the 5-year recurrence-free survival rates were 68.8% abd 61.1%, respectively. No significant differences were observed in 5-year overall survival rates and recurrence-free survival rates between AC and ASC patients (all >0.05).@*CONCLUSIONS@#Lymphovascular space invasion was more likely to occur in patients with ASC, but there was no significant difference in the prognosis between AC and ASC patients.

Embolization of uterine arteriovenous malformation

Background: uterine arteriovenous malformation is a rare but potential life-threatening source of bleeding. A high index of suspicion and accurate diagnosis of the condition in a timely manor are essential because instrumentation that is often used for other sources of uterine bleeding can be lead to massive hemorrhage

Case: we describe here a case of uterine arteriovenous malformation. A 32-year-old woman presented abnormal vaginal bleeding following the induced abortion. A diagnosis of uterine arteriovenous malformation made on the basis of Doppler ultrasonraphy was confirmed through pelvic angiography. The embolization of bilateral uterine arteries was performed successfully

Conclusion: uterine arteriovenous malformation should be suspected in patient with abnormal vaginal bleeding, especially who had the past medical history incluing cesarean section, induced abortion, or Dillation and Curethage and so on. Although angiography remains the gold standard, Doppler ultrasonography is also a good noninvasive technique

Analysis of the status of DACH1 gene promoter methylation in endometrial carcinoma and its clinical significance / 中华妇产科杂志

ObjectiveTo analyze the status of DACH1 gene promoter methylation and explore its association with the expression of DACH1 gene promoter methylation and clinical significance of endometrium carcinoma(EC).Methods From February 2004 to August 2008,a total of 80 EC tissue samples with comprehensive surgical pathology staging were collected and used for this study.Twenty normal endometrium tissues in 2008 were abtained from the fractional curettage because of dysfunctional uterine bleeding as control.All samples were confirmed pathologically.Methylation specific PCR (MSP) was performed to detect the promoter methylation of DACH1 gene,and analyze its influence on the expression of DACH1 and the relationship between DACH1 promoter methylation and clinicopathological factors in EC.DACH1 protein expression was detected by western blot.Chi-square test and Pearson test were used for statistical analysis.ResultsThe rate of promoter methylation of DACH1 gene in the EC tissues was significantly higher than that in the normal endometrium issues (30％ vs.5％,P ＜ 0.05).There was an association between the expression of DACH1 and DACH1 gene promoter methylation ( r =- 0.30,P ＜ 0.01 ).There was statistical difference between the methylation of DACH1 and the pathological grade ( P ＜ 0.05 ) or histological type ( P ＜0.05).But DACH1 gene methylation was not related with the age,stage,myometrial invasion depth and lymphnode metastasis (P ＞ 0.05 ).Conclusions DACH1gene promoter methylaion could lead to a decrease or absence in the DACH1 expression in EC.The promoter methylation of DACH1 gene may induce the inhibition of DACH1 expression,which might be one of the mechanisms of DACH1 gene inactivation in human EC.

Application of simultaneous morcellation in situ in laparoscopic myomectomy of larger uterine leiomyomas

To describe the efficiency, blood loss, operating time and mean hospital stay of enucleation of a large myoma by 'simultaneous morcellation in situ' [SMI] in laparoscopic myomectomy [LM]. Patients and Twenty-six patients with leiomyomas>9 cm in diameter were treated using LM and SMI from January 2006 to December 2009. Patient characteristics and operative data were collected and analyzed. The average operating time was 106.4 +/- 38.5 min [range 50-175 min]. The average blood loss was 278.2 +/- 164.6 ml [range 50-800 ml]. There was no other complication, and no patient underwent conversion to laparotomy. The average postoperative hospital stay was 5.4 +/- 0.2 days [range 5-7 days]. Our study confirmed that SMI is an efficient and safe way to remove large uterine myomas [>9 cm] during LM

Application of pathological diagnosis by rapid paraffin sections for biopsy in the diagnosis and treatment of cervical diseases / 中华妇产科杂志

Objective To evaluate the application of pathological diagnosis by rapid paraffin sections in the diagnosis and treatment of cervical diseases. Methods A total of 176 cases from our hospital between September 2009 and January 2010 with abnormal cervical cancer screening (including abnormal cytology result and high-risk HPV continuous positive) were randomly divided into 2 groups. Eighty-seven cases of them whose biopsy were got by Belinson forceps under the direction of colposcopy with rapid paraffin sections by ultrasonic histopathological rapid processor and BT transparent agents were selected as group A, while 89 cases with conventional paraffin sections were selected as group B. The production time and quality for paraffin sections were analyzed in the two groups. Those diagnosed as cervical intraepithelial neoplasia (CIN)Ⅱ or even worse and some special patients with CIN Ⅰ in the two groups received surgery, including loop electrosurgical procedure (LEEP) ,cold knife conization (CKC),.hysterectomy or radical hysterectomy.Tissue obtained after surgery was sent for routine pathological examination. If the results of postoperative routine pathological examination were inconsistent with the rapid or routine biopsy pathological examination,the heavier results were regard as the final diagnoses. The pathological results and diagnose accordance rates were recorded and compared between group A and group B. Results The quality of sections in two groups were all satisfied or basically satisfied to meet the diagnostic requirements. There were statistically significant difference in average production time between group A and B (40 minutes vs 24 hours, P 0. 05). Conclusion Bapid paraffin sections technology is safe, accurate and economical for rapid pathological diagnosis of cervical diseases, which is worthy for being widely used in hospitals.

Effect of extracelinlar signal regulated kinase signal pathway on apoptosis induced by MG262 in ovarian cancer cells / 中华妇产科杂志

Objective To investigate whether the proteasomes inhibitor MG262 exerts its anticancer function by inducing apoptosis in human ovarian cancer cells,and whether the extracellular signal regulated kinase (ERK) signaling pathway is involved in the regulation of apoptosis induction.Method Human ovarian cancer cell line SKOV3 was incubated with different concentrations of MG262 for 24 and 48 hours.Cell viability was evaluated with 3-(4,5-dimethyhhiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay at different time points of culturing.Flow cytometry was used to detect cell apoptosis rate.The expression of vascular endothelial growth factor (VEGF) was evaluated with western blot and enzyme-linked immtmosorbent assay (ELISA).Western blot was used to detect the expression of phosphorylated ERK(pERK) .Results The viability of SKOV3 cells was decreased by MG262 in a concentration-dependent fashion(P＜0.05).After 24 h incubation with MG262 at 1,10,20,40,60 and 80 nmol/L,the viability rates of SKOV3 were (94.6±3.1)%,(92.7±3.7)%,(89.5±7.7)%,(84.2±5.1)%,(82.0±7.4)%and(76.8±11.0) % respectively,and after 48 h incubation,those figures were further decreased to (91.3±10.1)%,(86.8±4.5)%,(74.6±4.2)%,(56.8±2.1)%,(49.3±4.5)% and (37.4±5.4) %,respectively(P＜0.05).Apoptosis rate of SKOV3 cells induced by MG262,PD98059 or their combination was (30.7±4.3)%,(26.8±8.6)% and (50.3±10.6)%,respectively,which were significantly different compared with controls (P＜0.05).In contrast to SKOV3 cells,apoptosis rate of 293T ceils induced by MG262,PD98059 or their combination was (14.5±5.3) %,(16.2±7.5) % and (10.8±7.3)%,respectively,which were not significantly different compared with controls (P＞0.05).pERK expression decreased gradually in a time-dependent manner. And wild-type p53 expression was not significantly different.There was no significant difference between experimental and control 293T cells(P＜0.05).In addition,MG262 down-regulated VEGF secretion and expression in SKOV3 ceils (P＜0.05).Conclusions Proteasome inhibitors can induce apoptosis and inhibit cell proliferation and angiogenesis through ERK signal pathway in SKOV3 cells.

Expression and significance of chemokine CXC receptor 3, 4 and their ligands at the early pregnancy decidua and villi / 中华妇产科杂志

Objective To explore the expression and significance of chemokine CXC reeeptor (CXCR)3 and CXCR4 and their ligands(CXCL)at the early pregnancy decidua and villi.Methods Decidual mononuclear cells were isolated from the normal decidua of 5-8 weeks pregnant women by lymphocyte separation medium in vitro.CD56+natural killer(NK)cells were purified by dynabeads cell sorter kiL Purity and phenotype of CD56+decidua NK cells were analyzed by fluorescence-activated eell sorter (FACS).Gene expression of CXCR3 and CXCR4 in decidua NK cells and CXCL9,CXCL10 and CXCL12 in early pregnancy decidua and villi was assessed bv RT.PCIZ Protein expression of CXCL9,CXCL10 in normal endometrium and early pregnancy decidua was characterized and quantified by streptavidin-biotin pemxidase chain reaction(SP)immunohistochemistry and computered image analysis system.Correlations between the gray degree of CXCL9 and CXCL10 and the number of CD56+NK cells in upper tissue were analyzed by Spearman's correlation ceefficient rank tesL Results The phenotype of 98.7%decidua NK cells was CD56bright.The genes of CXCR3 and CXCR4 were expressed in decidua NK cells and that of CXCL9 and CXCL1O were expressed in early pregnancy decidua and CXCLI2 in early pregnancy villi.CXCL9 and CXCL10 were expressed in the cytoplasm of surface epithelia,glandular epithelia and stromal cells of early pregnancy deeidua and were not expressed in villi by immunohistochemistry.The gray degree of CXCL9 and CXCL10 in the secretory phase endometrium(56±43,59±47)was stronger than that in the proliferative phase(16±18,8±14,P<0.05)and reached the highest(143±35,158±29,P<0.05)in the early pregnancy decidua.The number of cD+56 NK cell in the secretory phase endometrium(60±20)was more than that in the proliferative phase endometrium(23±4,P<0.05)and was the most in the early pregnancy decidua(114±15,P<0.05).The gray degree of CXCL9 in upper tissue had a positive correlation with the number of CD+56 cells(r=0.88,P<0.05)and that of CXCL10 had a similar pattern to CXCL9(r=0.86,P<0.05).Condusion The interactions between CXCL9,CXCL10 and CXCL12 expressed in decidua and villi and CXCR3,CXCR4 expressed in CD+56 decidua NK cells may influence the CD+56 NK cell recruitment at the maternal-fetal interface.

Effect of ursodeoxycholic acid on visceral yolk sac cell membrane fluidity and placental glutathione concentration in pregnant rats with intrahepatic cholestasis / 中华围产医学杂志

Objective To explore the effects of ursodeoxycholic acid (UDCA) on the fluidity of rat visceral sac and placental glutathione (GSH) concentration in rats with intrahepatic cholestasis. Methods Sixty rats were randomly divided into 3 groups (20 in each). Refined vegetable oil 2.5 ml/(kg?d) was given to the control group since the 13 days of pregnancy. The ICP treatment and non treatment group received either progesterone 75 mg/(kg?d) or 17? ethynylestradiol 1.25 mg/ (kg?d) from the 13th to 17th day, respectively. From the 17th day, the control and non treatment group were fed with 0.9% nitrachloride solution 5 mg/(kg?d) and the treatment group with UDCA 50 mg/(kg?d). All rats were sacrificed on the 21st day. The visceral yolk sac cell membrane and GSH concentration were measured Results The concentration of GSH in the ICP non treatment group (1.12?0.02 mmol/g protein) was significantly lower than that of the treatmentgroup (1.38?0.03 mmol/g protein) and the control group (1.56?0.07 mmol/g protein) ( P 0.05). The fetal death rate in treatment group (9.55%) and control group (1.97%) was significantly lower than that of the non treatment group (20.47%) ( P

Influences of active immunotherapy on T helper cell type 1 and 2 cytokines in women with unexplained habitual abortion / 中华妇产科杂志

Objective To investigate the influences of active immunotherapy on T helper cell (Th)1/Th2 type cytokines in women with unexplained habitual abortion(UHA) Methods A total of 55 patients with UHA were studied, including 30 cases after active immunotheraphy (AIT) and 25 cases without any therapy(NAIT). Fifteen cases of normal nonpregnant (NNP) women were selected as control group. Supernatants from trophoblast activated peripheral blood mononuclear cells (PBMC) of the three groups were tested by enzyme linked immunosorbent assay (ELISA) for interferon gamma (IFN ?), interleukin 2 (IL 2), IL 4, IL 10. Results (1) The levels of IL 2 and IFN ? in AIT group [(108?37) ng/L and (110 ?52) ng/L, respectively] were lower significantly than those in NAIT group[(223?85) ng/L and (326 ?92) ng/L, respectively]( P 0.05). (2) Twenty six women in AIT group got pregnant, but 8 women experienced pregnancy loss repeatedly whose IL 2?IFN ? levels were higher than those in other 18 women got successful pregnancy and IL 4,IL 10 levels lower than the latter. Conclusions UHA patients have Th1 type immunity to trophoblast and produce high level Th1 type cytokines which probably result in pregnancy loss. Active immunotheraphy could make a shift from Th1 to Th2 immunity, thus favoring the maintenance of pregnancy.

Gene transfer of CD_( 80)into a human ovarian cancer cell line and induction of cytotoxic T lymphocyte in vitro / 中华妇产科杂志

Objective To investigate the proliferation and cytotoxicity of cytotoxic T lymphocyte (CTL) induced by ovarian cancer cells transfected with a CD 80 gene containing retroviral vector Methods The ovarian cancer cell line TYK cells were transfected with retro virus vector PLXSN hCD 80 After geneticin (G418) selection, the CD 80 expression of the transfectants was confirmed by flow cytometry CTL was induced by co culture of CD 80 expressing TYK cells (TYK hCD 80 ) and peripheral blood mononuclear cells (PBMC) in the presence of anti CD 3 monoclonal antibody (McAb) Proliferation of PBMC was measured using 3?H Thymidine incorporation assay The lysis activity of CTL toward tumor cells was determined using methyl thiazolyl tetrazolium (MTT) assay Results After transfection and G418 selection, the CD 80 expression was proved by flow cytometry The highest rate of CD 80 expression was 84 9% The TYK cell line expressing high CD 80 was named TYK hCD 80 In the presence of anti CD 3 McAb,TYK hCD 80 significantly enhanced proliferation of PBMC than TYK cells ( 3H Thymidine incorporation, (40 604? 842) vs (8 000? 594) cpm ( P

Research on the method of culture and identification of embryonic stem cells from human primordial germ cells / 中国免疫学杂志

Objective:To study the cooperated effect of Human Embryonic Lung Fibroblast(HELF) feeder layer and LIF in the culture of human Embryonic Stem(hES) cells and establish the method of identifying hES cells from Primordial Germ Cells(PGCs).Methods:Embryonic lungs were mechanically disaggregated,then cultured to establish HELF feeder layer.Gonadal ridges and mesenteries of embryos were mechanically disaggeregated,then cultured and passaged in vitro.Comparing the growth characters of hES cells in different conditions.To identify hES cells through their biological characteristics.Results:The coactions of HELF feeder layer and LIF play an important role in proliferation and undifferentiation of hES cells in vitro.High levels of AKP and telomerase activity are associated with hES cells. The cultrued cells have been continuously passaged for more than two months and found to be karyotypically normal and stable.When differentiating,they form embryoid bodies(EBs).Conclusion:To avoid indection of the heterogeneous protein,HELF feeder layer, in the presence of LIF,can be used in culture of hES cells;hES cells from PGCs can be identified through their biological characteristic. [

Targeted killing effect of mucin-1 single chain antibody targeting, lentivirus-mediated suicide gene therapy and ganciclovir in mucin-1~+ ovarian epithelial carcinoma cells / 中华妇产科杂志

Objective To investigate the targeted killing effect of mucin 1 single chain antibody targeting, lentivirus mediated suicide gene therapy and ganciclovir(GCV) in mucin 1 + ovarian epithelial carcinoma cells Methods Mucin 1 single chain antibody targeting lentivirus produced by packaging cell line 293T transduced herpes simplex virus thymidine kinase (HSV tk) gene into the ovarian epithelial cancer cell line SKOV3 (MUC1 +) The infection effect was observed through fluorescence microscopy Polymerase chain reaction (PCR) and reverse transcription PCR (RT PCR) were resorted to demonstrate the successful transduction and transcription of the HSV tk gene After administration of GCV, changes of those cells were observed through optical microscopy The cytotoxicity efficacy of HSV tk/GCV system was evaluated by methyl thiazolyl tetrazolium method Results It was observed through fluorescence microscopy that anti MUC1 directed lentivirus can specificly infect MUC1 + ovarian cancer cells A fragment of 600 bp was generated through PCR and RT PCR which indicated successful transduction and transcription of the HSV tk gene in SKOV3 cells Changes of cells followed by administration of GCV were observed with optical microscopy Significant cytotoxicity efficacy of GCV to SKOV3 was observed Conclusions The HSV tk gene can be targetedly transducted into MUC1 + ovarian cancer cell line under the mediation of anti MUC1 directed lentivirus, and such HSV tk/GCV system has targetingly killing effect on MUC1 + cancer cells

Adenovirus - mediated Herpes Simplex Virus Thymidine Kinase Gene Transference and Combined Drug Therapy Leads to Opoptosis of Human Epithelial Ovarian Cancer Cells / 中华妇产科杂志

Objective To evaluate the treatment and apoptosis effect of adenovirus-mediated herpes simplex virus thymidine kinase (HSV 1-tk) gene transference followed by administration of ganciclovir (GCV) and acyclovir (ACV) on ovarian epithelial cancer cells. Methods Recombinant adenovirus was amplificated and purified by routine method. The expression of HSV 1-tk gene was assayed by polymerase chain reaction (PCR). The efficiency of recombinant Advtk transference was evaluated. The cytotoxicity efficacy of TYK cells that carry HSV 1-tk gene was evaluated followed by GCV、ACV administration after the transference of Advtk. The changes and apoptosis of TYK cells that carry HSV 1-tk gene were observed by means of analysis of DNA fragmentation and electronic microscopy. Results Adenovirus was amplificated and purified in large amount. PCR assay showed 404 bp special band. When the multiplicities of infection (MOI) was 100, the transduction rate was 98 9%. The inhibition rates of TYK cells that carry HSV 1-tk gene increased with the increase of MOI when the same concentration of GCV、 ACV were given. When the MOI was same, the inhibition rates were also increased with the increase concentration of GCV、ACV. Apoptosis of TYK cells that carry HSV 1-tk gene after administration of GCV was observed by means of analysis of DNA fragmentation and electronic microscopy. Conclusions The HSV 1-tk gene can effectively transfered into TYK cells by recombinant replicated-deficient adenovirus vector, GCV、ACV can effectively kill TYK cells that carry HSV 1-tk gene in vitro. Apoptosis may be the mechanism of the killing effect.

Effects of arsenic trioxide on different types of human ovarian cancer cell lines in vitro / 中国癌症杂志

Purpose:To study the effects of arsenic trioxide on the different types of human ovarian cancer cells growth in vitro.Methods:Methyl thiazolyl tetrazolium (MTT)was used to observe the growth inhibition rates of human ovarian cancer cell lines 3AO,SKOV 3 and TYK cells by various concentration arsenic trioxide at different times; Cell apoptosis percentage and cell cycles phase distribution of 3AO were measured by flow cytometry(FCM) assays; Apoptotic phenotype of SKOV 3 was observed by acridine dying. Results:Arsenic trioxide could inhibit the growth of 3AO?SKOV 3 and TYK effectively, depended on the action time and concentration of the medicine(P0.05). Within a certain range, 3AO cells apoptotic percentage induced by arsenic trioxide were enhanced in concentration- and time-dependent patterns(P

Inhibitory effects of angiostatin gene combined with antisense hypoxia inducible factor-1? gene transfection on implanted human ovarian carcinoma in nude mice / 中国肿瘤生物治疗杂志

Objective: To observe the synergistic inhibitory effect of angiostatin gene combined with antisense hypoxia inducible factor-1? (aHIF-1?) gene on implanted human ovarian carcinoma in nude mice. Methods: BALB/C nude mice were subcutaneously transplanted with SKOV3 tumor cells and the tumors were allowed to grow till the diameter reached 0.4 cm, then the mice were randomly divided into 4 groups: PcDNA3 control group, PcDNA3-Angiostatin group, PcDNA3B-aHIF-1? group and PcDNA3-Angiostatin+PcDNA3B-aHIF-1? group; plamids PcDNA3, PcDNA3-Angiostatin, PcDNA3B-aHIF-1? and PcDNA3-Angiostatin+PcDNA3B-aHIF-1? were injected intra-tumorally in the above groups, respectively. The tumor samples were harvested on the 7 th day after gene transfer. Angiostatin, HIF-1?, vascular endothelial growth factor (VEGF) and microvessel density (MVD) of tumors were determined by immunohistochemical methods. Tumor cell apoptosis was determined with TUNEL staining. Results:The growth of tumors of PcDNA3-Angiostatin+PcDNA3B-aHIF-1? group was significantly inhibited, with local low expression of HIF-1? and VEGF (lower than those of the other 3 groups). MVD in combined transfection group(13.6?2.3) was lower than that of Angiostain group (24.5?2.7); the apoptosis index in combined transfection group (5.32?0.62)was higher than those of Angiostatin group(2.89?0.45), aHIF-1? group(2.98?0.51)and contrl group(1.56?0.41). Conclusion: Our results suggest a synergestic effect between Angiostain gene and aHIF-1? gene in inhibiting implanted human ovarian tumors in nude mice, which may contribute to drug resistance in antiangiogenic therapy of tumors.

Anti-Tumor Study of pOSP1-HSVtk Gene Therapy by Polyethylenimine Mediated Transfection in Ovarian Cancer / 中国肿瘤生物治疗杂志

0.01). The tumor volume and the tumor weight were also significantly decreased in the treated group (P

VP22 Enhanced Intercellular Trafficking of HSV Thymidine Kinase Promoted an Effective Cell Killing Effect at Lower Concentration of Ganciclovir / 中国肿瘤生物治疗杂志

Objective: To explore the enhanced cell killing effect of HSV tk using VP22 intercellular traffciking. Methods: The chimeric genes were constructed by fusing a marker gene for the green fluorescent protein (GFP) or a prodrug enzyme gene for the Herpes simplex virus thymidine kinase (HSV tk) with that of VP22. After being sequenced, the fusion genes were transferred into 293T or COS7 cells. The transfection efficiency and intercellular trafficking were certified using Western blot and immunofluorescence.The cell proliferation was detected through MTT method in the different concentration of GCV and under indicated between transfected cells and untransfected cells. The supernatant of transfected cells was used to culture the untransfected cells to test whether the bystander effect could transferred by media. Results: The gene insertion was proved correct using PCR and DNA sequencing. When the fusion genes were transferred into 293T or COS7 cells at transfection efficiency of 25%～30%, fusion proteins were expressed and efficient intercellular trafficking was demonstrated.The VP22 HSV tk, as a prodrug enzyme fused with VP22, showed an amplified cell killing effect in the presence of GCV as low as 0.1 ?g/ml. Further quantification of the bystander effect showed that cell killing increased with higher proportion of VP22 HSV tk expressing cells. The bystander effect could not be transferred through media. Conclusion: These results clearly indicate that VP22 enhanced intercellular trafficking promotes tumor cell killing effect of HSV tk/GCV.