ABSTRACT
OBJECTIVE: This meta-analysis aimed to investigate the association between circulating human papillomavirus (HPV) cell-free DNA and oncological outcomes of cervical cancer patients. METHODS: Searches were performed in MEDLINE, Embase, and CENTRAL from their inception until 26 November 2023. Inclusion criteria were: (1) pathologically confirmed cervical cancer with available HPV test results; (2) detection of HPV cell-free DNA was performed in serum/plasma before or at end of treatment; (3) studies reported oncological outcomes of cervical cancer patients according to the levels of HPV cell-free DNA. Data extraction and study quality assessment were performed independently by two authors. Pooled hazard ratios and 95% confidence intervals were calculated using the inverse-variance method for survival outcomes. RESULTS: Five studies were finally included in this meta-analysis. Blood samples were collected from 167 patients before treatment, with 150 individuals available for analysis at the end of treatment. Furthermore, 82 patients with available samples at 3 months post-treatment were included in the analysis. The pooled results indicated a significant association between positive HPV cell-free DNA at end of treatment and worse progression-free survival in patients with cervical cancer (pooled hazard ratio: 5.49; 95 % confidence interval: 2.85-10.58; I2: 0 %). Similar findings were observed in patients with detectable HPV cell-free DNA at 3 months post-treatment (pooled hazard ratio: 7.86; 95 % confidence interval: 3.32-18.60; I2: 0 %). However, the detection of HPV cell-free DNA before treatment was not significantly associated with progression-free survival (pooled hazard ratio: 0.97; 95 % confidence interval: 0.55-1.71; I2: 0 %). CONCLUSION: Cervical cancer patients testing positive for HPV cell-free DNA at the end of treatment or 3 months post-treatment displayed significantly poorer oncological outcomes compared to those testing negative. Thus, personalized monitoring of HPV cell-free DNA holds promise as a prognostic biomarker for patients with cervical cancer.
Subject(s)
Carcinoma, Neuroendocrine , Carcinoma, Small Cell , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/diagnosis , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/surgery , Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Small Cell/pathology , Carcinoma, Small Cell/therapy , Carcinoma, Small Cell/surgery , Carcinoma, Small Cell/diagnosis , Middle Aged , Adult , AgedABSTRACT
BACKGROUND: Minimally invasive radical hysterectomy has been reported to increase the risk of cancer relapse and death compared with open surgery in women with early-stage cervical cancer. The use of a uterine manipulator is considered one of the risk factors. OBJECTIVES: To investigate whether women with early-stage cervical cancer treated with minimally invasive radical hysterectomy without using uterine manipulator have oncological outcomes similar to those of open surgery. SEARCH STRATEGY: Searches were performed in MEDLINE, Embase and CENTRAL from their inception until 31 March 2022. SELECTION CRITERIA: Inclusion criteria were: (1) randomised controlled trials or observational cohort studies published in English, (2) studies comparing minimally invasive radical hysterectomy without using a uterine manipulator with open radical hysterectomy in women with early-stage cervical cancer, and (3) studies comparing survival outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently conducted data extraction and assessed study quality. We calculated the hazard ratios (HR) and the 95% confidence intervals (CI) using the inverse variance approach for survival outcome. MAIN RESULTS: Six observational studies with 2150 women were included. The minimally invasive surgery group had a significantly higher risk of cancer relapse compared with open surgery group (HR 1.55, 95% CI 1.15-2.10). CONCLUSIONS: Minimally invasive radical hysterectomy without using a uterine manipulator resulted in an inferior recurrence-free survival compared with open radical hysterectomy in the treatment of women with early-stage cervical cancer.
Subject(s)
Laparoscopy , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/pathology , Neoplasm Staging , Neoplasm Recurrence, Local/etiology , Hysterectomy/methods , Minimally Invasive Surgical Procedures , Retrospective Studies , Laparoscopy/methodsABSTRACT
Chemotherapy serves as the first choice in clinic to treat advanced gastric cancer. However, emerging evidence indicated the induction of drug resistance and cancer stem cells occasionally by chemotherapy, which seriously limit the therapeutic effects, but the regulatory mechanism remains unclear. Here we treated two human gastric cancer cell lines SGC7901 and BGC823 with 5-Fluorouracil (5-Fu) or Cisplatin (DDP) in vitro. The survived cells showed significant increase of drug resistance, cell stemness and cytokine GM-CSF expression and secretion. As such, GM-CSF was applied to stimulate gastric cancer cells, followed by the subpopulation of CD133 + CSC analysis, sphere formation assay and stemness genes expression analysis. As a result, CSCs showed induction by GM-CSF treatment. A gastric cancer animal model further indicated that the gastric cancer cells significantly promoted tumor growth after GM-CSF treatment in vivo. High-throughput miRNA and mRNA sequencing analyses identified a subset of miRNAs and mRNAs under regulation of both 5-Fu and GM-CSF in gastric cancer cells, including upregulation of miR-877-3p and downregulation of SOCS2. Targeted overexpression or knockdown of miR-877-3p in gastric cancer cells revealed the oncogenic function of miR-877-3p in regulating gastric cancer by suppressing target gene SOCS2. Jak2/Stat3 signaling pathway, as a downstream target of SOCS2, showed activation in vitro and in vivo after treatment with miR-877-3p or GM-CSF. Our findings not only revealed a novel mechanism through which chemotherapy induced CSCs in gastric cancer via GM-CSF-miRNA-Jak2/Stat3 signaling, but also provided an experimental evidence for appropriate dose reduction of adjuvant chemotherapy in treatment of cancer patients.
ABSTRACT
OBJECTIVE: To investigate the expression level of silencing information regulatory 2 (SIRT2) in cervical cancer and CIN tissues and its clinical significance. METHODS: Immunohistochemistry was carried out to examine the expression of SIRT2 in 262 cases of cervical cancer tissues, 75 cases of precancerous lesions and 75 cases of normal cervical tissues, and the clinical implications of SIRT2 was further analyzed. The protein expression level of SIRT2 in 40 cervical cancer fresh tissue samples and 20 normal cervical tissue samples was detected by Western blot. shRNA-SIRT2 virus was transfected into HeLa cells to obtain the SIRT2-down-regulated HeLa cells. And the influence of down-regulation of SIRT2 on cell proliferation and migration was investigated by MTT and Scratch test. RESULTS: Immunohistochemical results showed that SIRT2 protein expression level gradually increased in cervical cancer, CIN and normal cervix tissues (P < 0.001). Western blot confirmed that SIRT2 expression level was higher in cervical cancer tissues than in normal cervix tissues (P < 0.001). The expression level of SIRT2 in cervical cancer was correlated with some factors, such as lymph node metastasis, histological type, clinical staging and HPV infection (P < 0.05). At the same time, it was independent of some factors including age, differentiation degree, pelvic metastasis, whether involving the cervical interstitial and the involvement depth and whether involving the neck junction and vaginal ends (P>0.05). Mortality in SIRT2 high expression patient group was higher than that of SIRT2 low expression patient group (P < 0.05). shRNA interference technique could effectively inhibit the expression level of SIRT2 in HeLa cells (P < 0.05). MTT assay and Scratch test indicated that down-regulation of SIRT2 expression inhibited the proliferation and migration of HeLa cells (P < 0.05). CONCLUSION: SIRT2 may play a promoting role in the progress of cervical cancer, and SIRT2 may be related to the development of malignant degree of cervical cancer, and the inhibition of SIRT2 expression may be a potential therapeutic target for cervical cancer.
Subject(s)
Sirtuin 2/metabolism , Uterine Cervical Dysplasia/metabolism , Uterine Cervical Neoplasms/metabolism , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , HeLa Cells , Humans , Lymphatic MetastasisABSTRACT
OBJECTIVE: To study the expression of ubiquitin C-terminal hydrolase-L3 (UCH-L3) in epithelial ovarian cancer (EOC) tissues, and to analyze the relationship between UCH-L3 expression and the clinic pathological characteristics and prognosis of EOC patients. METHODS: Immunohistochemical analysis was performed to evaluate UCH-L3 expression in different ovarian epithelial tissue specimens. The correlation between UCH-L3 expression and clinical pathologic parameters, prognosis and of EOC was statistically analyzed. RESULTS: The expression level of UCH-L3 in EOC was higher than that in benign ovarian tumor and normal ovary (P < 0.05). The positive expression level of UCH-L3 in late FIGO group, high-level group, group with intraperitoneal metastasis were significantly higher than that in early FIGO group (P=0.006), low-level group (P=0.001), group without intraperitoneal metastasis (P=0.032). There was no significant difference in survival time between the high and low expression groups of UCH-L3. CONCLUSION: UCH-L3 may play a role in EOC pathogenesis and progression.
Subject(s)
Carcinoma, Ovarian Epithelial/genetics , Cysteine Endopeptidases/genetics , Ovarian Neoplasms/genetics , Female , Humans , Prognosis , Ubiquitin ThiolesteraseABSTRACT
Ultra-high-performance liquid chromatography coupled with tandem high-resolution mass spectrometry (UHPLC-HR-MSn ) method was used to analyze the constituents of Fufang Gancao Tablets and its main metabolites in rat plasma. Rat plasma was collected both before and after oral administration of Fufang Gancao Tablets. After solid phase extraction, ACQUITY UHPLC BEH C18 (2.1 mm×100 mm, 1.7 µm) was used with 0.1% formic acid-acetonitrile solution as the mobile phase for gradient elution. The chemical components in Fufang Gancao Tablets and their prototypes and metabolites in plasma samples were analyzed by LTQ-Orbitrap equipped with an ESI ion source in a positive ion mode. Based on the accurate mass measurements, the retention time and mass fragmentation patterns, a total of 55 compounds were tentatively identified from Fufang Gancao Tablets, including 42 flavonoids, 9 triterpenes and 4 alkaloids. Furthermore, metabolites in rat plasma after oral administration of Fufang Gancao Tablets were also analyzed. A total of 26 compounds were identified, including 20 prototypes and 6 metabolites mainly through metabolic pathways of hydroxylation, glucuronide conjugation, and sulfate conjugation, etc. Our results showed that the ultra-high-performance liquid chromatography coupled with linear ion trap quadrupole Orbitrap high resolution mass spectrometry (UHPLC-LTQ-Orbitrap) could comprehensively elucidate the chemical constituents of Fufang Gancao Tablets and their migrating components in rat plasma, providing scientific basis for further studying the metabolism process and pharmacodynamic substance of Fufang Gancao Tablets.
Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Animals , Flavonoids , Rats , Tablets , Tandem Mass SpectrometryABSTRACT
OBJECTIVE: To determine the expression of miR-130a in patients with epithelial ovarian cancer and its association with platinum resistance. METHODS: 32 patients with platinum resistance and 30 patients without platinum resistance were recruited in this study. Real-time PCR was performed to detect the expression of miR-130a in the serum samples of the patients. ELISA was used to measure the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and B-cell lymphoma-2 (BCL-2). RESULTS: Platinum-resistant patients had significantly higher levels of expression of miR-130a and BCL-2, and lower level of PTEN than platinum-sensitive patients (P < 0.05). The expression level of miR-130a increased with increased severity in histological classification and appearance of lymph node metastasis in the platinum-resistant patients (P < 0.05). CONCLUSION: MiR-130a may mediate the generation of platinum resistance in epithelial ovarian cancer through inhibiting PTEN to activate PI3K/AKT signaling pathway and increasing BCL-2 to inhibit tumor cell apoptosis. MiR-130a may be a new potential target of gene therapy in platinum-resistant ovarian cancers.
Subject(s)
Drug Resistance, Neoplasm , MicroRNAs/blood , Neoplasms, Glandular and Epithelial/genetics , Ovarian Neoplasms/genetics , Platinum , Apoptosis , Carcinoma, Ovarian Epithelial , Female , Humans , Neoplasms, Glandular and Epithelial/blood , Ovarian Neoplasms/blood , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolismABSTRACT
OBJECTIVES: To investigate the expressions of Livin and phosphate and tension homology deleted on chromsome ten (PTEN) protein in the cancerous tissues of ovary endometriosis. METHODS: Immunohistochemistry EliVision was used to examine the expressions of Livin and PETN protein in 19 samples of ovary endometriosis cancerous tissues, 30 samples of ovary endometriosis tissues and 30 samples of ovarian benign tumor tissues. RESULTS: The positive expression rate of Livin in ovary endometriosis cancerous tissues (68%) was obviously higher than that in ovary endometriosis tissues (36%) and benign tumor tissues (13%)( P<0.05). The positive expression rate of PTEN in ovary endometriosis cancerous tissues (16%) was obviously lower than that in ovary endometriosis tissues (65%) and benign tumor tissues (80%)( P<0.01). There was no correlations between positive expressions of Livin and age, clinical stage, grading, histological type and lymphatic metastasis of ovary endometriosis cancer ( P>0.05), the same result was also found for PTEN. Livin and PTEN expression presented an obviously negative correlation in ovary endometriosis cancer ( r=-0.559, P=0.001). CONCLUSIONS: Up-regulation of Livin expression and down-regulation of PTEN may be involved in the occurrence and development of ovary endometriosis cancerization.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Endometriosis/genetics , Inhibitor of Apoptosis Proteins/genetics , Neoplasm Proteins/genetics , Ovarian Neoplasms/genetics , PTEN Phosphohydrolase/genetics , Female , Humans , Immunohistochemistry , Lymphatic MetastasisABSTRACT
OBJECTIVE: To determine the regulatory effects and associated mechanisms of miR-130a on cisplatin resistance in ovarian cancer A2780 cell lines (including cisplatin sensitive A2780s and its resistant A2780/DDP cells). METHODS: A2780s and A2780/DDP cells were divided into four groups, and treated with lipo2000 (Lip), miR-negative (miR-NC) control, miR-130a-mimics (miR-130a-M increasing the expression of miR-130a and the agent), and miR-130a-inhibitor (miR-130a-I downregulating miR-130a expression), respectively. The proliferation of cells and their sensitivity to cisplatin were detected by MTT assay. RT-PCR and western blot were performed to examine the levels of MDR1, PTEN mRNA and proteins. RESULTS: The expressions of MDR1 mRNA and P-gp in the A2780/DDP cells were significantly higher than those in the A2780s cells. However, no differences in the expressions of PTEN mRNA and proteins were detected between the two cell lines. Over-expressions of miR-130a had no effect on cell proliferation, but increased the resistance of the cells to cisplatin and up-regulated the expressions of MDR1 mRNA and P-gp in both cell lines. Down-regulated miR-130a did not affect cell proliferations, but enhanced the sensitivity of the cells to cisplatin, inhibited the expressions of MDR1 mRNA and P-gp and increased the expression of PTEN proteins. CONCLUSION: MiR-130a expression may be associated with cisplatin resistance of ovarian cancer cells. MiR-130a inhibitor can reverse the cisplatin resistance by upregulating the expression of PTEN proteins and down-regulating P-gp in A2780 cell lines. MiR-130 may become a new potential target of genetic therapy for cisplatin-resistant ovarian cancers.
Subject(s)
Cisplatin/pharmacology , Drug Resistance, Neoplasm/genetics , MicroRNAs/genetics , Ovarian Neoplasms/genetics , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Female , Humans , MicroRNAs/antagonists & inhibitors , MicroRNAs/metabolism , Ovarian Neoplasms/pathology , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
OBJECTIVE: To determine the expression of miR-130a in cisplatin resistant cell lines of ovarian cancer and its impact on cisplatin resistance. METHODS: Cisplatin resistant ovarian cancer cell lines were established by stepwise selection with gradual increase of cisplatin. MTT assay was applied to indentify the cisplatin resistant cell lines and determine their resistance index. The expression of miR-130a was measured by SYBR green real-time PCR. RESULTS: The resistance index of A2780/CIS1, A2780/CIS2 and SKOV3/CIS was 30.2, 5.3 and 24.5 respectively. The SYBR green real-time PCR showed that miR-130a was over-expressed in all of the cisplatin resistant cell lines (P < 0.05). The expression of miR-130a was 30.51 times higher in A2780/CIS1, 4.87 times higher in A2780/CIS2 and 24.43 times higher in SKOV3/CIS than in their parental cell lines (P < 0.05), which was almost equally reflected in their resistance index. CONCLUSION: The over expression of miR-130a is associated with cisplatin resistance of ovarian cancer. Inhibiting miR-130a expression may help reverse the cisplatin resistance of ovarian cancer. miR-130a is expected to be a new potential target of genetic therapy for cisplatin resistant ovarian cancer.
Subject(s)
Cisplatin/pharmacology , Drug Resistance, Neoplasm/genetics , MicroRNAs/metabolism , Ovarian Neoplasms/genetics , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Female , Humans , MicroRNAs/genetics , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathologyABSTRACT
OBJECTIVE: To evaluate the inhibitory effect of artemisnin on surgically induced endometriosis in rat model and the possible mechanism related to cellular apoptosis and microvascular angiogenesis. METHODS: Surgically induced endometriosis model was established with female rats, and then the rats were divided into four groups: high dose artemisinin [300 mg/(kg x d)), low dose artemisinin [150 mg/(kg x d)], danazol [160 mg/(kg x d)] and solvent control group After daily administration of the above agents for 4 weeks, the rats were sacrificed, then the implant size of ectopic endometrium was measured and appotosis index (AI), Bcl-2 and MVD in ectopic endometrium were evaluated with S-P immunohistochemistry. RESULTS: Compared with solvent control, both artemisinin (high and low quality) and danazol decrease the size of implants significantly (P < 0.05), and there was no significant difference among the three treatment groups. AI of the three treatment groups increased significantly, while Bcl-2 and MVD decreased significantly (P < 0.05). AI of both artemisinin groups were significantly higher than that of danazol group, but Bcl-2 level was lower. CONCLUSION: Artemisnin inhibits surgically induced endometriosis in rats, and the possible mechanism may be related to stimulatation of cellular apoptosis and inhibition of angiogenesis.
Subject(s)
Artemisinins/therapeutic use , Endometriosis/drug therapy , Angiogenesis Inhibitors/therapeutic use , Animals , Apoptosis/drug effects , Endometriosis/etiology , Endometriosis/pathology , Female , Random Allocation , Rats , Rats, WistarABSTRACT
OBJECTIVE: To investigate the expression of endothelin-1 (ET-1) and its receptors (ET(A)R, ET(B)R) in patients with endometriosis and to explore the possible role of them in the pathogenesis of endometriosis. METHODS: The tissues of ectopic and eutopic endometrium were collected from 48 cases of endometriosis (EM), while the control samples were eutopic endometrium from 13 cases of cervical intraepithelial neoplasia (CIN). The expressions and locations of ET-1, ET(A)R, ET(B)R were measured by immunohistochemical staining. RESULTS: The expression levels of ET-1 and ET(A)R of EMs group, either in eutopic or in ectopic endometrium, were higher than those of the control group (All P<0.01). Moreover, the expression levels of ET-1 and ETAR in eutopic endometrium were higher than those in ectopic endometrium. There were significant correlations between the expression of ET-1 and ETAR in EMs group, either for eutopic or for ectopic endometrium (r=0.970, 0.968 respectively, All P<0.05). There was no significant difference in the expression level of ET(B)R among eutopic endometrium of EMs, ectopic endometrium of Ems and eutopic endometrium of control group (All P>0.05). There was no significant difference in the expression level of ET-1, ET(A)R and ET(B)R in proliferative phase and secretory phase in both EMs group and control group (All P>0.05). The expression levels of ET-1, ET(A)R and ET(B)R were not associated with r-AFS staging of endometriosis (All P>0.05). CONCLUSION: By the way of combining ET(A)R, ET-1 may play a important role in the pathogenesis of endometriosis.
Subject(s)
Endometriosis/metabolism , Endometrium/metabolism , Endothelin-1/metabolism , Receptor, Endothelin A/metabolism , Adult , Endometriosis/etiology , Female , Humans , Middle AgedABSTRACT
OBJECTIVE: To determine the clinicopathologic characteristics and prognostic factors that may be used to predict the poor outcome of patients with borderline ovarian tumors. METHODS: All cases with borderline ovarian tumors treated in the West China Second University Hospital from January 2001 to June 2007 were analyzed retrospectively for clinicopathologic features, treatment parameters and outcome of treatment. Univariate and multivariate analyses were used to assess independent prognostic factors using the logistic regression model. RESULTS: The median age of 234 patients was 40.1 years with a range of 14 to 80 years. There were 101 (43.2%), 94 (40.2%), 19 (8.1%), 12 (5.1%), 8 (3.4%) cases of serous, mucinous, mixed, endometrioid and clear cell tumors, respectively. Out of 234 cases, 182 (77.8%) underwent laparotomy and 45 (19.2%) underwent laparoscopy. Seven women underwent laparoconversion. Fertility sparing surgery was performed on 119 cases (50.9%) and radical surgery was performed on 115 cases (49.1%). Totally 161 (68.8%) patients had stage I, 19 (8.1%) had stage II, 54 (23.1%) had stage III, and none had stage IV disease. Sixty-four women received postoperative chemotherapy. The median follow-up was 40 months with a range of 8 to 78 months. Recurrence was found in 26 cases (11.1%) during follow-up, and no tumor-related death was reported. The logistic regression model showed that surgery procedure (OR = 2.304, P = 0.024), cyst rupture (OR = 2.213, P = 0.038), stage (OR = 4.114, P < 0.01), microinvasion (OR = 2.291, P = 0.046) and peritoneal implants (OR = 2.101, P = 0.016) were the five independent prognostic factors affecting recurrence. CONCLUSIONS: Although patients with borderline ovarian tumors have an excellent prognosis, the risk of recurrence remains in some patients. Emphasis should be put on these patients with high risk factors and preventive strategies should be taken to prevent their progression.
Subject(s)
Cystadenocarcinoma, Mucinous/pathology , Cystadenocarcinoma, Serous/pathology , Ovarian Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/surgery , Cystadenocarcinoma, Mucinous/mortality , Cystadenocarcinoma, Mucinous/surgery , Cystadenocarcinoma, Serous/mortality , Cystadenocarcinoma, Serous/surgery , Female , Follow-Up Studies , Gynecologic Surgical Procedures/methods , Humans , Laparoscopy , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Neoplasm Staging , Ovarian Neoplasms/mortality , Ovarian Neoplasms/surgery , Prognosis , Retrospective Studies , Young AdultABSTRACT
OBJECTIVE: To prove the PLLA-PTX' efficacy on growth, apoptosis of ovarian cancer cell line SKOV3, and to study the controlled release roles of PLLA for PTX. METHODS: Cultured cells of human ovarian Carcinoma cell Line SKOV3 were treated with PLLA-PTX microparticles and PTX only separately, untreated cells as the control. The proliferation of SKOV3 cells were determined by MTT assay with the morphologic change observed under inverted phase contrast microscope, the apoptosis of cell were demonstrated by FCM and in situ TUNEL technique. RESULTS: The anti-tumor activity of PLLA-PTX microparticles was stronger than PTX alone. A time-dependent and dose-dependent growth inhibition was abserved. At 0.05 micromol/L drug concentration, SKOV3 cell viability experiment demonstrated that the drug formulated in the microparticles was more effective than that formulated in PTX. PLLA-PTX microparticles can increase G2/M period percentage, interrupt the cell cycle proceeding, and inhibit the tumor cells'growth through cell apoptosis. Positive staining for the presence of apoptosis were obtained in SKOV3 cells with PLLA-PTX microparticles. CONCLUSIONS: PLLA-PTX microparticles have strong anti-tumor activity and obviously controlled released effectiveness. It shows longer and stronger controlled anti-tumor activity than paclitaxel alone.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Lactic Acid/pharmacology , Ovarian Neoplasms/pathology , Paclitaxel/pharmacology , Polymers/pharmacology , Cell Line, Tumor , Cell Proliferation , Delayed-Action Preparations , Female , Humans , Particle Size , PolyestersABSTRACT
OBJECTIVE: To evaluate the therapeutic effect of quercetin on the rat endometriosis models and the relationship between the inhibition effect and the expression of HSP70 and VEGF. METHODS: A surgical model to simulate endometriosis was established and the rats were divided into four groups. After 3 weeks of daily administration of quercetin, dazazol, combined quercetin+dazazol, and placebo, the potential rule of quercetin to inhibit endometriosis in rats were evaluated by measuring the implants, examining the histology and detecting the expression of heat shock protein 70 (HSP70) and vascular endothelial growth factor (VEGF) in ectopic endometrium with immunohistochemistry. RESULTS: Compared to placebo, quercetin [100 mg/(kg x d)], dazazol [36 mg/(kg x d)], and combined quercetin + dazazol decreased the size of implants significantly respectively, and there was no significant difference among the three groups. HSP70 and VEGF were both significantly reduced by quercetin or combination treatment, but no significant difference was seen between quercetin and combination treatment groups. CONCLUSION: Quercetin inhibits surgically induced endometriosis in rats, and the possible mechanism is to inhibit the expression of HSP70 and VEGF.
Subject(s)
Endometriosis/drug therapy , HSP70 Heat-Shock Proteins/metabolism , Quercetin/therapeutic use , Vascular Endothelial Growth Factor A/metabolism , Animals , Danazol/pharmacology , Danazol/therapeutic use , Endometriosis/etiology , Female , HSP70 Heat-Shock Proteins/genetics , Quercetin/pharmacology , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/geneticsABSTRACT
OBJECTIVE: To observe whether human papillomavirus 16 (HPV16) E6-specific small interfering RNAs (siRNAs) can be employed to inhibit the growth of cervical cancer cell line, and to investigate the associated mechanism. METHODS: RNAi was performed using synthetic small interfering RNAs transferred into CaSki cell line by lipofectamine. The cell growth curves, live cell ratio and inhibition ratio of cells were measured by using cell counting. At various time points of post-transfection, the distributions of cell cycle, the expression levels of HPV16 E6, p53, p21 mRNA and proteins were detected by using flow cytometry (FCM) and real-time quantitative reverse transcription-polymerase chain reaction (real-time RT-PCR). RESULTS: The growth inhibition of E6 siRNA to CaSki cells was demonstrated after cells treated with E6 siRNA. No substantial G1 arrest was observed by FCM analysis. For 24 hours after cell transfection, the level of E6 mRNA was decreased by 20. 11 folds compared with control (P < 0.05). However, p53 and p21 mRNA levels appeared unaffected. 48 hours after cell transfection, the expression level of E6 protein was efficiently decreased, but the P53 and P21 protein levels increased in comparison. CONCLUSIONS: The inhibitory effect of HPV16 E6 siRNA to CaSki cell maybe due to specially and efficiently silence E6 mRNA expression, decrease the degradation of wild type P53 protein, and then recover the function activity of P53 protein.
Subject(s)
Cell Cycle , Cell Proliferation , Oncogene Proteins, Viral/metabolism , RNA, Small Interfering/genetics , Repressor Proteins/metabolism , Uterine Cervical Neoplasms/pathology , Cell Line, Tumor , Female , Humans , Oncogene Proteins, Viral/genetics , RNA Interference , Repressor Proteins/genetics , Transfection , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/virologyABSTRACT
OBJECTIVE: To evaluate the effects of siRNA on the inhibitions of mRNA and P-gp expression of ovarian cancer cell with high expression of multidrug resistance gene (MDR1). METHODS: The siRNA was transferred into ovarian cancer cell line OVCAR8/TR. The real time RT-PCR and flow cytometry were used respectively to determine the expression of mRNA or P-gp of MDR1. RESULTS: The inhibition of mRNA-84% expression occurred at 48 h after cell transfection, and the inhibition of P-gp-85.23% expression occurred at 72 h after cell transfection. Afterward the inhibitions to mRNA and P-gp expressions gradually returned to the normal levels. The amounts of mRNA and P-gp expression had no difference between negative control and untransfected cells. CONCLUSION: RNA interference presents in the human ovarian cancer cell, siRNA can effectively inhibit the expression of mRNA and P-gp of MDR1. The RNAi may represent a new approach for the treatment of MDR1-mediated drug resistance.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Drug Resistance, Neoplasm/genetics , Ovarian Neoplasms/genetics , RNA Interference , RNA, Small Interfering/genetics , Cell Line, Tumor , Female , Humans , RNA, Messenger/metabolism , RNA, Neoplasm/metabolismABSTRACT
Glassy carbon electrode (GCE) is covalently modified with aspartic acid (Asp). The modified electrode is used for the simultaneous electrochemical determination of hydroquinone (HQ) and catechol (CC) and shows an excellent electrocatalytical effect on the oxidation of HQ and CC by cyclic voltammetry (CV) in 0.1 mol/L acetate buffer solution (pH 4.5). In differential pulse voltammetric (DPV) measurements, the modified electrode could separate the oxidation peak potentials of HQ and CC present in binary mixtures by about 101 mV though the bare electrode gave a single broad response. A successful elimination of the fouling effect by the oxidized product of HQ on the response of CC has been achieved at the modified electrode. The determination limit of HQ in the presence of 0.1 mmol/L CC was 9.0 x 10(-7) mol/L and the determination limit of CC in the presence of 0.1 mmol/L HQ was 5.0 x 10(-7) mol/L. The proposed method has been applied to the simultaneous determination of HQ and CC in a water sample with simplicity and high selectivity.
Subject(s)
Aspartic Acid/chemistry , Biosensing Techniques/methods , Carbon/chemistry , Catechols/analysis , Hydroquinones/analysis , Biosensing Techniques/instrumentation , Electrochemistry , Electrodes , Oxidation-Reduction , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To evaluate the effects of two commonly used non-steroidal anti-inflammatory drugs (NSAIDs) Celecoxib and Aspirin on the SKOV3 cell growth, apoptosis and neoplasm genesis of ovarian cancer in vitro and vivo. METHODS: The proliferation of SKOV3 cells were determined by MTT assay, the apoptosis of cell were measured by flow cytometry (FCM), and the cell morphologic changes were observed under inverted phase contrast microscope. Xenografted nude mice models of human ovarian cancer were established, and then randomly allocated to treatment or control group, which was administered with either Celecoxib at the dosage of 10, 25, 50 mg/kg or distilled water alone (control) orally daily for 56 d. The mice weight, tumor volume and drug side effects were detected. RESULTS: A dose-dependent inhibition of proliferation of SKOV3 cell appeared after Celecoxib or Aspirin administered for 24 h, and Celecoxib had more inhibiting efficiency to cell growth than Aspirin did. The inhibitory concentration 50% (IC50) in this assay for Celecoxib was 5X 10(-5) mol/L,whereas for Aspirin was 7X 10(-3) mol/L. With cell morphology the "vacuole" presented in the cytoplasm. In contrast to the control, the apoptotic rates (47. 1% and 15. 7%) of SKOV3 were increased after treatment with Celecoxib (5 X 10(-5) mol/L) and Aspirin(7 X 10(-3) mol/L). In nude mice, the average volume of tumor from control mice was (3. 283+/- 0. 432) cm(3) as compared with (2. 457+/- 0. 224) cm(3), (2. 198+/- 0. 500) cm(3), (2. 017+/-0. 166) cm' from Celecoxib mice (10, 25, 50 mg/kg), P<0. 05, and the rates of tumor growth inhibited by 3 Celecoxib dosages to SKOV3 cell burden mice were 25. 20%, 33. 00% and 38. 60%, in a dose-and time-dependent manner, and histopathologic examinations of kidney, liver, stomach and bowel showed no abnormality, with implying no untoward side effects. CONCLUSION: Both COX-2 specific inhibitor Celecoxib and non-selective inhibitor Aspirin can potentially inhibit the tumor growth and induce apoptosis of SKOV3 cells, and the effect of Celecoxib is more potential than that of Aspirin.