1.miR-205 and cancer
Xinxin HOU ; Meng ZHAO ; Guiyu ZHANG
Journal of International Oncology 2012;39(10):732-734
miR-205 is differentially expressed in tumor tissues and is closely related to tumorigenesis and tumor metastasis.miR-205 can regulate the biological behaviors of tumor cells such as cell proliferation,differentiation,in situ invasion and distant metastasis by post-transcriptional regulation through binding to targeted genes.Additionally,further research of miR-205 may be helpful for tumor diagnosis,targeted therapy and prognosis.
2.Effects of PPARγ gene expression on cell migration, invasion, and proliferation in endometrial cancer cells
Xinxin HOU ; Meng ZHAO ; Guiyu ZHANG
Chinese Journal of Obstetrics and Gynecology 2014;49(5):360-365
Objective To observe the effects of differentially expressed peroxisome proliferatoractivated receptor γ (PPAR γ) on cell migration,invasion and proliferation of endometrial cancer cells.Methods Two endometrial cancer cell lines ECC-1 (ER positive) and KLE (ER negative) cells were used in this study.To up or down regulate PPARγ expression,the transient transfection by using PPARγ expression vector (PPARγ expression vector group) and PPARγ small interference RNA (PPARγ siRNA group) were done.The negative control groups were cells transfected by nonsence sequence siRNA (siRNA non sence sequence group) or empty vector (empty vector group).At the same time,cells only added with liposome were used as blank control group.Then,quantitative real time (RT)-PCR and western blot were used to detect PPARγexpression both in mRNA and protein levels.To assess the expression levels of Wnt signaling pathway,western blot was performed to analysis protein levels of β-catenin and C-myc.The effects on cell migration,invasion and proliferation using in vitro transwell migration,invasion assays and cell counting kit-8 (CCK-8) assay were further be examined.Results After transfection for 48 hours,quantitative RT-PCR and western blot showed that PPARγmRNA (5.18 ± 0.99,4.54 ± 0.89) and protein (1.45 ± 0.12,1.30 ± 0.13) expression levels significantly increased and the protein levels of β-catenin (0.44 ± 0.06,0.46 ± 0.04) and C-myc (0.42 ± 0.08,0.30 ± 0.11) decreased in PPAR γ expression vector group,while in PPARγ siRNA group,PPARγ mRNA (0.48 ± 0.08,0.53 ± 0.11) and protein (0.41 ±0.04,0.49 ±0.05) expression levels decreased and the protein levels of 3-catenin (1.18 ±0.12,0.89 ±0.07) and C-myc(0.91 ±0.08,0.77 ±0.12) increased significantly compared with control groups (all P < 0.05).In vitro migration and invasion assay indicated that the migratory and invasive cell numbers of PPARγ expression vector group (ECC-1:129 ± 9,63 ± 12 ; KLE:119 ± 9,68 ± 16) were significantly decreased,while the migratory and invasive cell numbers of were PPARγ siRNA group (ECC-1:201 ± 14,142 ±9 ; KLE:170 ± 11,138 ± 7) increased significantly compared with those in control groups(all P < 0.05).CCK-8 assay showed that A values (0.66 ±0.14,0.78 ±0.06) in PPARγexpression vector group were lower than those in control groups,and in PPARγ siRNA group,A values (1.42 ± 0.16,1.23 ± 0.04) were higher than those in control groups,and there were statistically significant difference among them (all P < 0.05).Conclusion Up-regulated PPARγ gene expression could inhibit endometrial cancer cell migration,invasion and proliferation abilities,and down-regulated PPARγ gene expression could promote endometrial cancer cell migration,invasion and proliferation abilities.
3.Effects of propofol treatment on neuroapoptosis in primary cultured cortical neurons
Jianli LI ; Wei LIANG ; Xinxin PANG ; Honghai WU ; Yanning HOU
The Journal of Clinical Anesthesiology 2016;32(5):491-494
Objective To investigate the effect of propofol exposure on neuroapoptosis in pri-mary cultured cortical neurons and its mechanisms.Methods Cortical neurons were primarily cultured for seven days,then divided into two groups:control group (treated with equal volume of 20% in-tralipid),propofol-treated group (treated with 500 μmol/L propofol).The neurons were treated for 12 h.The neuron viability was determined by MTT.Neuroapoptosis was identified by Hoechest 33 258 dying.Mitochondrial membrane potential was measured by the fluorescent dye rhodamine 123 (Rh123).Western blot was performed to detect the level of cyt-c and cleaved-caspase-3.Results Neu-rons survival rate (54.4%±6.4%)in the propofol group was significantly lower than that of control group (99.8% ± 4.1%) (P < 0.05 ), the rate of neuronal apoptosis (46.5% ± 5.3%) was significantly higher than that of control group (7.2%±0.9%)(P <0.05),mitochondrial membrane potential (59.6%±4.3%)was significantly lower than that of the control group (99.9% ± 5.7%) (P <0.05 ),cyt-C protein level (0.38 ± 0.03 )was significantly higher than that of control group (0.1 5±0.02)(P < 0.05 ),level of cleaved-caspase-3 protein level (0.46 ± 0.04)was significantly higher than that of control group (0.13±0.02)(P <0.05).Conclusion Propofol induces neuroapo-tosis in primary cultured cortical neurons,which is associated with the decreased level of MPP and the increase levels of cyt-c and cleaved-caspase-3.
4.Correlations among the expressions of PPARγ, ERα, and ERβin endometrial carcinoma
Xinxin HOU ; Meng ZHAO ; Hongxia WANG ; Guiyu ZHANG
Chinese Journal of Clinical Oncology 2013;(17):1029-1033
Objective:To investigate the expressions of peroxisome proliferator-activated receptor gamma (PPARγ), estrogen re-ceptor alpha (ERα), and estrogen receptor beta (ERβ) in endometrial carcinoma and to analyze their correlations and clinical signifi-cance. Methods:Immunohistochemical assay and Western blot were used to detect the expressions of PPARγ, ERα, and ERβin normal endometrial tissues and well-differentiated, moderately differentiated, and poorly differentiated endometrial carcinomas. Results:PPARγexpression was significantly lower in endometrial carcinoma than in the normal endometrium and was intimately associated with cli-ni-copathologic variables. ERαexpression gradually decreased in moderately and poorly differenti-ated endometrial carcinomas. How-ever, no significant differences were found between the normal endometrium and well-differentiated endometrial carcinoma. ERβex-pression only decreased in the poorly differentiated endometrial carcinoma. No significant association was observed between ERβand clinicopathologic variables. Pearson correlation analysis showed a significant positive cor-relation between the expressions of PPARγand ERα. No correlations were observed between the expressions of ERαand ERβand between that of ERβand PPARγ. Conclusion:The expression lev-els of PPARγand ERαwere significantly associated with the clinicopathologic stage of endometrial carcinoma, and have essential functions in endometrial tumorigenesis and tumor progression.
5.Protective effect of 17β-estradiol against propofol-induced apoptosis of primarily cultured cortical neurons
Jianli LI ; Deyun YIN ; Yunxin WANG ; Xinxin PANG ; Honghai WU ; Yanning HOU
Journal of Medical Postgraduates 2015;(9):925-928
Objective 17β-estradiol is known to have a neuroprotective effect.The aim of this study was to investigate the effects of 17β-estradiol on propofol-induced neuroapoptosis in primarily cultured cortical neurons. Methods Rat cortical neurons were primarily cultured for 7 days and randomly divided into groups A ( vehicle control) , B, and C, treated with equal volume of 20%intralipid, 500 μmol/L propofol, and 500 μmol/L propofol +0.1 μmol/L 17β-estradiol, respectively.At 12 hours after treatment, the morphology of the neurons was observed under the microscope, their survival rate calculated by MTT, their apoptosis was deter-mined by FCM assay, and their mitochondrial membrane potential measured by fluorescent dye rhodamine 123. Results Compared with group A, group B showed a significantly reduced number of neurons, lack of 3-dimensional appearance, unclear contour, and fractured neuron axons, but a remarkable improvement was observed in the propofol-induced morphological damage in group C.The survival rate of the neurons and the mitochondrial membrane potential were markedly decreased in group B ([52.3 ±5.2]% and [59.1 ± 5.3]%) as compared with groups A ( [99.9 ±3.6]%and [99.6 ± 5.8]%) and C ([90.1 ±7.2]%and [89.2 ±7.1]%) (both P<0.01 ) , while the rate of neuroapoptosis significantly increased in group B ([43.4 ±4.6]%) in comparison with A ([3.1 ±0.2]%) and C ([22.3 ±3.2]%) (both P<0.01). Conclusion 17β-es-tradiol can protect against propofol-induced apoptosis of primarily cul-tured neurons by inhibiting the reduction of their mitochondrial membrane potential.
6.Association between single nucleotide polymorphism of BARD1 gene and BRCA1 gene mutation in epithelial ovarian cancer
Weiling LIU ; Jiuzhou ZHAO ; Zhizhong WANG ; Bing DONG ; Yangyang HOU ; Xinxin WU ; Yongjun GUO
Chinese Journal of Obstetrics and Gynecology 2017;52(6):403-410
Objective To investigate the relationship between single nucleotide polymorphism (SNP) of BARD 1 gene and BRCA1 gene in epithelial ovarian cancer (EOC).Methods Nineteen EOC patients with BRCA1 gene mutation and 50 EOC cases without BRCA1 gene mutation between January 2016 and October 2016 were collected,and all EOC were diagnosed by pathological method.BARD1 gene variants were detected by next generation sequencing (NGS).The SNP of BARD1 gene was analyzed by Pearson linear correlation.Logistic regression analysis was used to research the clinicopathologic features and BRCA1 gene mutation associated with BARD1 gene SNP.Pearson's chi-square test was used to analyze the association between BARD1 gene Val507Met,Arg378Ser and Pro24Ser with different clinicopathologic features and BRCA1 gene mutation risk.Results (1) Eight BARD1 gene variants were found in 69 ovarian cancer patients,in which Val507Met,Arg378Ser and Pro24Ser were common variants,and the rate of mutation were all 54% (37/69).(2) There was a significant linear correlation among Val507Met,Arg378Ser and Pro24Ser (all P<0.01).(3) Obvious differences were found in Val507Met,Arg378Ser and Pro24Ser of BARD1 gene between BRCA1+ and BRCA1 (all P<0.05).(4) No differences were found between BARD1 gene Val507Met,Arg378Ser and Pro24Ser and the clinicopathologic features (all P>0.05),while obvious differences were found in BRCA1 gene mutation compared to the controls group.The risk of BRCA1 mutation in Val507Met and Arg378Ser were more evident in subjects with negative family history,positive menopause history,negative tubal ligation,onset age (≤60 years old) and sensitivity to platinum-based chemotherapy in EOC (all P<0.05),while Pro24Ser was only more evident in positive menopause history of EOC (P<0.05).Conclusions BARD1 Val507Met,Arg378Ser and Pro24Ser are the common genotypes,which are associated with BRCA1 mutation in EOC.The family history,menopause history,tubal ligation,onset age and sensitivity to platinum-based chemotherapy have effects on BARD1 SNP in the risk of BRCA1 gene mutation.
7.Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer
Weiling LIU ; Zhizhong WANG ; Jiuzhou ZHAO ; Yangyang HOU ; Xinxin WU ; Wu LI ; Bing DONG ; Tingting TONG ; Yongjun GUO
Chinese Journal of Obstetrics and Gynecology 2017;52(1):26-31
Objective To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1)The BRCA genes were detected by next-generation sequencing (NGS) method. (2)The serum tumor markers included carcinoembryonic antigen (CEA), CA125, CA199, and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t-tests, Pearson′s chi square test, Fisher′s exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics(FIGO)stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM). Results (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA199, and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found (P>0.05), but the level of CA125 was much higher in BRCA mutation group than that in controls (t=-3.536,P=0.003). Further linear regression analysis found that there was a significant linear correlation between CA125 and HE4 group (r=0.494,P<0.01), and the same correlation as CEA and CA199 group (r=0.897,P<0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA+and BRCA- group (P>0.05), while significant differences were found in CA125 and sensitivity to platinum-based chemotherapy between the patients with BRCA mutation and wild type (P<0.05). The multiple factors analysis showed that the high level of CA125 was a independent risk factor of BRCA mutations in sporadic HGSOC (P=0.007). Conclusion The combination of CA125 with BRCA have great clinical significance, the mutation of BRCA gene could guild the clinical chemotherapy regiments.
8.Preliminary research of combining LARS and semi-joint replacement for malignant tumor around the knee in children
Shuangwu DAI ; Xinxin SHAO ; Haomiao LI ; Zixiong LEI ; Ming LU ; Changhe HOU ; Shaohua DU
Chinese Journal of Orthopaedics 2018;38(6):370-377
Objective To study the preliminary effect of combining ligament advanced reinforcement system (LARS) and semi-joint replacement for malignant tumor around the knee in children.Methods 9 cases of malignant tumor around the knee (5 boys and 4 girls) from February 2015 to May 2017 were analyzed respectively.The average age was 9.2 years old (ranged from 5 to 12 years).The follow-up time was 6 to 28 months,with an average of 13.5 months.The preoperational biopsy diagnosis respectively were Ewing sarcoma (3 cases) and osteosarcoma (6 cases).According to Enneking staging system,all 9 cases were staged as ⅡB.The planned courses of standardized preoperative neoadjuvant chemotherapy were successfully given to all patients on time.All patients were given tumor extensive resection and modular prosthesis replacement.Suitable length prosthesis were prepared according to CT and MRI.LARS were annularly bundled to the prosthesis.Then residual patella ligaments,cruciate ligaments,collateral ligaments,capsules and muscles were tightly sutured to LARS.Adjuvant chemotherapy and functional exercise were given after operation.Bone healing,limb discrepancy,and complications were regularly recorded.Functional outcomes were assessed by the system of the Musculoskeletal Tumor Society (MSTS) and the range of motion (ROM) of both knee joints.Results All patients successfully received standardized chemotherapy.In all courses of chemotherapy,bone marrow all restored.No other major complications occurred during chemotherapy.Primary healing of incisions were obtained.No obvious limb discrepancy.The average limb length discrepancy was 2.9±1.8 cm (0.5~6.4 cm),the femur was 1.9±1.0 cm (0.6~3.9 cm),the tibia was 0.8±0.5 cm (0.2~2.0cm).The distance between the lower limb alignment and the center of the knee was 0.3±0.1 cm (0.2~0.6 cm).MSTS score was 24.6±3.2 of the last follow-up,and 21.4± 1.9 of preoperation,the difference was statistically significant (t=2.71,P=0.03).ROM of the knee were 71.7°± 18.2° at the last follow-up,and 69.1 °± 17.9° before operation,and the difference was statistically significant (t=3.261,P=0.01).No infection,snapping knee,limp,dislocation,periprosthesis fractures,prosthetic broken or loosening.2 case had lung metastasis and still survived.NO local recurrence or other metastasis cases.Conclusion LARS combined with semijoint replacement for the treatment of malignant tumor around the knee in children have a satisfactory postoperative joint function recovery and simple surgical technique and fewer complications,and preserve the contralateral osteophytes to minimize the occurrence of limb inequality,but the long-term efficacy needs further follow-up.
9.Research on collection, preservation and resource utilization of clinical isolates
Xinxin LU ; Jianyu ZHAO ; Shaoya ZHANG ; Mei WANG ; Qianqian ZHOU ; Wenjun SUI ; Zhenjun LI ; Xuexin HOU ; Qiang WEI ; Mengnan JIANG
Chinese Journal of Laboratory Medicine 2021;44(11):1076-1081
Strain-resource engineering is often considered as an important infrastructure of microbiology related research and industry. The western developed countries took the lead in establishing the classical microbial resource utilization method, and continuously improved the preservation system, species annotation technology and global sharing mechanism, which realized the expansion and reserve of biological resources since end of the 19th century. The rich and diversified germplasm resources, standard strains and production strains not only have important economic values, but also maintain the advantages of scientific research, bioeconomy (such as antimicrobial agents, vaccines, detection reagent development and standard development, etc.) and national security. Although there has been a lot of progress in related research in recent years, compared with developed countries, there is still a big gap in related fields in China. The investment and top-level design in this area lag far behind the western developed countries, and it is not commensurate with the current level of economic and social development in my country. Drawing lessons from the practice of WFCC and WDCM (World Data Center for Microorganisms, Global microbial data Center, affiliated to WFCC), for the purpose of collecting new clinical species/strains, this paper puts forward some suggestions on the identification, preservation and upload system of isolates.
10. A retrospective study of the BiRd regimen in the treatment of relapsed/ refractory multiple myeloma
Xuelian LIU ; Lu LI ; Qinglin SHI ; Lijuan CHEN ; Xinxin CAO ; Jian LI ; Aijun LIAO ; Dehui ZOU ; Jingnan SUN ; Sujun GAO ; Wei LI ; Jian HOU ; Fengyan JIN
Chinese Journal of Hematology 2017;38(10):837-841
Objective:
To evaluate efficacy of the BiRd regimen, a combination of clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients with relapsed/refractory multiple myeloma (RRMM) .
Methods:
Patients with RRMM treated with BiRd between September 11, 2013 and August 1, 2016 at six centers were included to evaluate overall survival rate (ORR) , clinical benefit rate (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as adverse events.
Results:
Of 30 patients with RRMM, 27 patients were evaluable, and ORR and CBR were 51.9% (14/27) and 66.7% (18/27) respectively, including 1 sCR (3.7%) , 3 CR (11.1%) , 3 VGPR (11.1%) , and 7 PR (25.6%) . In 13 patients with prior Rd, ORR and CBR were 38.5% (5/13) and 61.5% (8/13) respectively, of which 5 patients with ≥MR carried high-risk cytogenetic[ (e.g.17p- or t (4;14) ] together with at least one of other adverse-prognostic cytogenetic (e.g.13q- and/or 1q21+) . In 24 patients with prior bortezomib-based therapy, ORR and CBR were 45.8 and 62.5%, respectively. With a median follow-up time of 14.9 (range 1.0-33.8) months, the median PFS and OS were 12.0 (95%