1.Mechanism of AMPK-enhanced chemosensitivity of breast cancer MCF-7/adr cells to adriamycin
Wenxian CUI ; Keqing XU ; Yuanguo LI ; Guijin CHEN ; Xiaoqun LU
China Oncology 2016;26(11):908-915
Background and purpose: AMP-activated protein kinase (AMPK) plays an important role in the regulation of cell metabolism and energy balance and is associated with cell proliferation, survival and multiple signaling pathways. Recent reports found that AMPK is involved in tumor suppression and drug resistance. The aim of this study was to explore the effect of AMPK on the anti-tumor effect of adriamycin and underlying mechanism in breast cancer MCF-7/adr cells. Methods:The anti-proliferative effects of adriamycin was detected by methyl thiazolyl tetrazolium (MTT) assay in MCF-7/adr, MCF-7/adr-vector and MCF-7/adr-AMPKαcells. The cell morphology in each group was stained with the lfuorescent dye Hoechst 33528, and the effects on apoptosis induction were examined by lfow cytometry (FCM). The intracellular concentration of adriamycin was detected by lfuorescence assay. The resis-tance-and apoptosis-related proteins were analyzed by Western blot. Results:The growth of breast cancer MCF-7/adr cells was inhibited by adriamycin in a dose-and time-dependent manner. The IC50 values at 24 and 48 h were (36.8±2.1) and (28.8±1.3) μg/mL, respectively. AMPKαover-expression enhanced the cytotoxic effect of adriamycin in MCF-7/adr-AMPKαcells in a dose-and time-dependent manner. Its IC50 values at 24 and 48 h were (16.0±0.7) and (4.2±0.2) μg/mL, respectively. Fluorescent morphological assay showed that AMPKαoverexpression contributed to adriamycin induced apoptosis in MCF-7/adr-AMPKαcells. After treatment with 1.0 μg/mL adriamycin for 48 h, the apoptosis rates of MCF-7/adr, MCF-7/adr-vector and MCF-7/adr-AMPKα cells were (12.0±1.4)%, (12.7±1.6)% and (32.0±4.2)%, respectively, indicating that overexpression of AMPKα enhanced the adriamycin-induced apoptosis in MCF-7/adr cells. Fluorescence microplate assay showed that over expression of AMPKαsigniifcantly increased the intracellular accumulation of adriamycin, in a concentration dependent manner. Western blot analysis showed that, compared with MCF-7/adr and MCF-7/adr-vector cells, the expressions of Bax, caspase-3 and cleaved PARP proteins were increased. Meanwhile, Bcl-2 and P-gp protein expressions were decreased in MCF-7/adr-AMPKαcells. Furthermore, the release of cytochrome c from mitochondria into the cytosol was also observed in MCF-7/adr-AMPKαcells. Conclusion:AMP-Kαoverexpression can enhance the chemosensitivity of breast cancer MCF-7/adr cells to adriamycin through inhibiting the drug effux transporter and regulating the expression of apoptosis-related proteins.
3.Paroxysmal nocturnal hemoglobinuria with cerebral venous sinus thrombosis:a case report and literature review
Wenxian LU ; Xiaomeng DONG ; Yaozhi HU ; Jinbo CHEN
International Journal of Cerebrovascular Diseases 2015;(2):156-160
Paroxysmalnocturnalhemoglobinuria(PNH)isadefectdiseaseofacquiredclonal hematopoietic stem cel s. It can be expressed as hemolytic anemia, hemoglobinuria, and venous thrombosis. Cerebral venous sinus thrombosis (CVST) is a rare but serious complication of PNH. Here we report a PNH patient with CVST and reviewthe relevant literature. For patients who have the risk factors for CVST and neurological symptoms, such as headache and increased intracranial pressure, should early conduct brain imaging examination and make the diagnosis clear, and give an active treatment in the aspects of anticoagulation, dehydration, eliminating the causes of disease, and controling complications.
4.Development and evaluation of a real-time fluorescent quantitative polymerase chain reaction assay for detecting human Herpesvirus-8 viral load
Hui WANG ; Yan HUI ; Tao LIU ; Wenxian LIU ; Junhua WANG ; Xiaomei LU ; Renyong LIN ; Hao WEN ; Xing WANG
Chinese Journal of Infectious Diseases 2010;28(7):413-417
Objective To establish a real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) for detection of human Herpesvirus-8 (HHV-8) viral load. Methods pMD19-T recombinant vectors inserted with an open reading frame (ORF) 26 of HHV-8 or β-actin gene were constructed respectively. A sensitive RT-qPCR method was established and optimized. The effectivity of the method was evaluated by determining the HHV-8 viral loads in 30 (formalin fixed, paraffinised)biopsy samples of Kaposi's sarcoma. Results The key factors for optimizing the method included anneal temperature and extension. The standard curve showed that the Ct value of ORF26 and β-actin had a good linear relationship (r2 >0.990) with the standard samples. The melt curve and electrophoresis showed the specificity of our study. The sensitivity of this method was very high and the detection rate could reach 100%. The viral loads were significantly higher in patients with classic Kaposi's sarcoma compared to patients with acquired immunodeficiency syndrome-associated Kaposi's sarcoma(69.18 va 8. 63, x2 =7.950,P=0.005).Conclusions The established RT-qPCR method is highly sensitive, which can be used as a routine assay for detecting HHV-8.This system offers a good platform for diagnosing other causative organism.
5.Efficacy and safety of multiple-dose 5-HT3 receptor antagonists in preventing multi-day-based and highly emetogenic chemotherapy-induced nausea and vomiting
Han WANG ; Hongxue WANG ; Weimin XIE ; Fanghui QIN ; Yongkui LU ; Wenxian ZHOU ; Jing TANG ; Yan LIU ; Aihua TAN
Chinese Journal of Clinical Oncology 2017;44(13):667-672
Objective:To evaluate efficacy and safety of multiple-dose tropisetron plus dexamethasone (DXM) versus palonosetron plus DXM for chemotherapy-induced nausea and vomiting. (CINV) in patients received multiple day-based highly emetogenic chemotherapy. Methods:Cancer patients who were receiving multiday-based highly emetogenic chemotherapy were randomly assigned to AB or BA groups. A randomized, cross self-control ed method was applied. Patients in AB group received palonosetron (0.25 mg) 30 min before chemotherapy on day 1 and 3 or additional day 5 in the first cycle;and with tropisetron (5 mg) 30 min before chemotherapy on day 1, 2, and 3, or sup-plementary days (day 4 and 5) in the second cycle. Patients in BA group were treated with tropisetron in the first cycle and with palonosetron in the second cycle. Tropisetron and palonosetron were administered with DXM (10 mg) on day 1, followed by additional doses (5 mg) on days 2 to 5. Palonosetron group comprised patients in the AB group in the first cycle and BA group in the second cycle, whereas tropisetron group included patients in the AB group in the second cycle and BA group in the first cycle. Efficacy and safety of tropisetron versus palonosetron in preventing CINV were evaluated. Results:Ninety-one patients were included in analyses. At day 3, 4, and 5, incidence rates of nausea in the palonosetron group reached 28.6%, 30.8%, and 24.2%, respectively, and those of the tropisetron group totaled 42.8%, 47.3%, and 39.6%, respectively (P<0.05). At day 4, 5, and 6, incidence rates of vomiting in the palonosetron group measured 28.6%, 18.7%, and 5.5%, respectively, and those of the tropisetron group reached 42.9%, 34.1%, and 14.3%, respectively (P<0.05). From day 4 to day 5, day 6 to day 7, and day 1 to day 7, the palonosetron group yielded significantly lower incidence rates of nausea and vomiting than tropisetron group (P<0.05). Rate of rescue treatment in the palonosetron group was lower than that in tropisetron group (13.2%vs. 24.2%, P=0.057). No statistical difference in toxicities was observed between the two groups. Conclusion:Palonosetron plus DXM features better efficacy than that of tropisetron plus DXM against delayed CINV induced by multiple day-based highly emetogenic chemotherapy, which was well tolerated in the two treatments.
6.Effect of different concentrations of human amniotic homogenate supernatant on the proliferation of rat Schwann cells
Liang LIU ; Lei WANG ; Yalin TONG ; Yongliang MO ; Lu LV ; Yunpeng CHEN ; Wenxian YANG ; Lifang LV ; Qiu ZHAN ; Fujun ZHU ; Haiming XIN ; Zhenyu GONG
Chinese Journal of Tissue Engineering Research 2014;(20):3218-3222
BACKGROUND:Schwann cells are important celllines in the process of repairing peripheral nerve injury, and human amniotic homogenate supernatant is shown to secrete a variety of cytokines, which could promote the proliferation of Schwann cells.
OBJECTIVE:To investigate the effect of different concentrations of human amniotic homogenate supernatant on the proliferation of rat Schwann cell96.
METHODS:Schwann cell96 was cultured with high-glucose DMEM containing 20%fetal bovine serum, and the second generation of Schwann cell96 was applied for experiments. The cultured cells were divided into five groups according to different volume fractions of human amniotic homogenate supernatant (0%, 10%, 15%, 20%, 25%) in the medium.
RESULTS AND CONCLUSION:The total protein concentration of human amniotic homogenate supernatant was 675μg/mL, in which the concentration of epidermal growth factor, basic fibroblast growth factor and vascular endothelial growth factor were respectively (470.625±2.546), (4.121±0.026) and (0.172±0.002) ng/L. At 1-7 days, the cellproliferation rate of the 10%and 15%concentration groups was greater than that in 20%and 25%concentration groups (P<0.05);10%and 15%concentrations promoted cellproliferation, while 20%and 25%concentrations inhibited cellproliferation. There were no significant difference in the viability of Schwann cell96 between the control group and the experimental group (P>0.05). Low concentrations (10%, 15%) of human amniotic homogenate supernatant promote the proliferation of Schwann cell96, while high concentrations (20%, 25%) of human amniotic homogenate supernatant inhibit cellproliferation.
7.Management and prognosis of primary retroperitoneal tumors
Song LIU ; Peng SONG ; Feng SUN ; Xiaofeng LU ; Meng WANG ; Wenxian GUAN
Chinese Journal of General Surgery 2023;38(12):900-904
Objective:To summarize the clinical characteristics of primary retroperitoneal tumors (PRT).Methods:All PRT cases undergoing surgical resection during recent 10 years at our center were retrospectively analyzed.Results:Tumors in all 92 cases were of malignant in 64 cases, borderline in 10 and benign PRT in 18, among which liposarcoma and leiomyosarcoma were the most common types. The tumor size and Ki-67 was significantly higher in malignant compared to borderline or benign PRT. The multifocal rate was 50%, en-bloc resection rate was 72%, R 0 rate was 61%, and combined organ resection rate was 41% in malignant PRTs. Small intestine and the colon were the most frequently resected organs. During 9.3 years of follow-up period, the 1-, 3- and 5-year cumulative reoperation rate of malignant PRT was 10.6%, 44.7% and 62.9%, respectively, and the median re-operation period was 4.0 years. The 1-, 3- and 5-year cumulative survival rate was 90.1%, 73.0% and 64.2%, respectively, and the median survival period was 6.1 years. None of postoperative borderline or benign PRT recurred or needed re-operation or deceased. Conclusion:Most of PRTs were malignant, presenting themsehies as a challenge to surgery with unfaror prognosis.
8.Effects of different therapies on coronary artery disease.
Shuzheng LÜ ; Wenxian LIU ; Xiantao SONG ; Yundai CHEN ; Hong LIU ; Liying CHEN ; Yanling LU ; Xin CHEN ; Rui TIAN ; Jinrong ZHANG
Chinese Medical Journal 2003;116(9):1341-1344
OBJECTIVETo analyse the effects of different therapies on coronary artery disease (CAD).
METHODSA total of 1055 patients who suffered from CAD diagnosed by coronary angiography were divided into three groups, namely pure drug therapy, percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) groups. Follow up was carried out from March to May in 2001, and the major adverse cardiac events (MACEs) including death, no-lethal myocardial infarction (MI) and revascularization were observed. In long-term observation, angina reoccurred, and their improvement was evaluated. The short-term period was defined as the duration of 30 days after discharge, and the long term period was defined as the duration from 30 days after discharge.
RESULTSIn the long-term period, the recurrences of angina both in PCI group and CABG group were lower than pure drug group (P 0.018, 0.002 respectively). No differences about long-term endpoint events were observed among these three groups (P > 0.05). Forty-two patients suffering from left main coronary disease were intervened by the three therapies, and there was no death or MI both in PCI and CABG groups, three patients died and suffered from AMI in pure drug therapy group (P = 0.015). In the short-term period, mortality in CABG group (5.77%) was higher than those in the other two groups (1.91% for PCI, and 1.40% for medical therapy, P = 0.002), and no obvious difference observed in the latter two groups. No significance was concluded about the recent MI among this three groups (P = 0.357). There were no differences on revascularization in these three groups.
CONCLUSIONSPercutaneous coronary interventions can not only reduce the attack of angina but also improve the life quality of patients, however it can not improve the long-term existence but left main CAD.
Adult ; Aged ; Angina Pectoris ; etiology ; Angioplasty, Balloon ; Coronary Artery Bypass ; Coronary Disease ; drug therapy ; surgery ; therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; etiology ; Treatment Outcome
9.Clinical analysis on platinum-based combined chemotherapeutical regimens for treating relapsed or refractory non-Hodgkin lymphoma
Hongxue WANG ; Meilin CHEN ; Fanghui QIN ; Wenxian ZHOU ; Yuxian JIA ; Jun CHEN ; Hong CEN ; Yu'an XIE ; Yongkui LU ; Weimin XIE
Chongqing Medicine 2018;47(5):618-621,625
Objective To evaluate the efficacy and adverse reactions of platinum-based combined chemotherapeutical regimens in treating relapsed or refractory non-Hodgkin lymphoma(NHL).Methods The clinical data of 68 patients with relapsed or refractory NHL treated with platinum-based combined chemotherapeutical regimens in the Affiliated Tumor Hospital of Guangxi Medical University from January 2008 to December 2014 were retrospectively analyzed.The curative effect of related regimens,adverse reactions and related influence factors were analyzed.Results Sixty-eight cases received 283 cycles of chemotherapy.In all cases,11 cases(16.18 %) achieved the complete response(CR),31 cases(45.59 %) achieved the partial response(PR),the overall response rate(ORR) was 61.76%;the median progression-free survival(PFS) was 6.51 months(95%CI:4.97-8.04 months).ORR and PFS in the cases of stage Ⅱ-Ⅲ,IPI score 0-2 and receiving only one chemotherapeutical regimen were superior to those in the cases of corresponding subgroup(P<0.05);ORR and PFS had no statistical difference between the B cells lymphoma and Tcells lymphoma(P>0.05).The medion PFS in the combined R group was 11.16 months,which was longer than 5.84 months in the non-combined R group(P =0.004).The major adverse events (stage Ⅱ-Ⅲ) included leukopenia (41.18 %),thrombocytopenia (27.94%),hemoglobin decrease(11.76%),vomiting(8.82%) and diarrhea(1.47%).Conclusion The platinum-based combined chemotherapeutical regimens are effective with good safety in the treatment of relapsed or refractory NHL.
10.Preliminary efficacy of video-assisted anal fistula treatment for complex anal fistula.
Hailong LIU ; Yihua XIAO ; Yong ZHANG ; Zhihui PAN ; Jian PENG ; Wenxian TANG ; Ajian LI ; Lulu ZHOU ; Lu YIN ; Moubin LIN
Chinese Journal of Gastrointestinal Surgery 2015;18(12):1207-1210
OBJECTIVETo evaluate the preliminary efficacy of video-assisted anal fistula treatment (VAAFT) for complex anal fistula.
METHODSClinical data of 11 consecutive patients with complex anal fistula undergoing VAAFT in our department from May to July 2015 were reviewed. VAAFT was performed to manage the fistula under endoscope without cutting or resection.
RESULTSVAAFT was successfully performed in all the 11 patients. The internal ostium was closed using mattress suture in 10 cases, and Endo-GIA stapler in 1 case. The mean operative time was (42.0±12.4) min, mean hospital stay was (4.1±1.5) d. Complication included bleeding and perianal infection in 1 case respectively. After 1 to 3.2 months follow-up, success rate was 72.7%(8/11), and no fecal incontinence was observed.
CONCLUSIONVideo-assisted anal fistula treatment is an effective, safe and minimally invasive surgical procedure for complex anal fistula with preservation of anal sphincter function.
Fecal Incontinence ; Humans ; Length of Stay ; Minimally Invasive Surgical Procedures ; Operative Time ; Rectal Fistula ; Sutures