OBJECTIVETo investigate the role of RLIP76 in regulating multi-drug resistance in small cell lung cancer (SCLC), and to analyze the relationship between its expression and prognosis.

METHODSThe expressions of RLIP76 protein and gene were detected by Western blotting and real-time PCR (RT-PCR) in both the chemosensitive SCLC H69 cell line and chemoresistant H69AR cell line, respectively. siRNA was transfected into the H69AR cells to inhibit RLIP76 expression, and eGFP-RLIP76 was transfected into the H69 cells to enhance RLIP76 expression. The drug-sensitivity of cells to chemotherapeutic drugs (ADM, DDP, VP-16) were detected by CCK8 assay. The expression of RLIP76 in the SCLC tissues was detected by immunohistochemistry. The relationship of RLIP76 expression with clinicopathological features and prognosis of the patients was analyzed.

RESULTSThe expression of RLIP76 in H69AR cells was 13.675 ± 0.983, significantly higher than 1.074 ± 0.107 in the H69 cells (P < 0.01). The drug-sensitivities of H69AR cells to chemotherapeutic drugs were significantly increased when the expression of RLIP76 was down-regulated (P< 0.001). The sensitivities of H69 cells to chemotherapeutic drugs ADM, DDP and VP-16 were significantly decreased after transfection with eGFP-RLIP76 up-regulating the RLIP76 expression (P = 0.003). The positive expression rates were 61.3% and 9.4% in the SCLC tumor tissues and para-cancerous tissues, respectively (P < 0.01). The expression of RLIP76 was significantly correlated with clinical stage, chemosensitivity and overall survival of the SCLC patients (P < 0.05).

CONCLUSIONSOur results suggest that RLIP76 is involved in the regulation of small cell lung cancer multidrug resistance. RLIP76 may serve as a potential target gene to evaluate the chemosensitivity and clinical prognostic for small cell lung cancer.

ATP-Binding Cassette Transporters ; metabolism ; physiology ; Antineoplastic Agents ; pharmacology ; Cisplatin ; pharmacology ; Down-Regulation ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Etoposide ; pharmacology ; GTPase-Activating Proteins ; metabolism ; physiology ; Humans ; Lung Neoplasms ; drug therapy ; metabolism ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Small Cell Lung Carcinoma ; drug therapy ; metabolism ; Transfection ; Up-Regulation

Objective To investigate the efficacy of sorafenib alone or combination with transarterial chemoembolization(TACE)and percutaneous local cryotherapy(PLCT)for advanced hepatocellular carcinoma patients without operation opportunity. Methods Sixty-four advanced hepatocellular carcinoma patients were selected as our subjects,who were underwent treatment of sorafenib alone or combination with TACE and PLCT. Thirty-two cases with sorafenib therapy were served as sorafenib group and another 32 cases with sorafenib in combination with transarterial chemoembolization and PLCT were served as combination group. All patients were followed up for 6 - 32 months. The treatment efficacy and tumor development were recorded. Results All surgeries of the patients were succeed and no death or serious operation complications occurred. Of 64 patients, 11 were achieved a complete remission( CR),31 cases with partial remission( PR),14 cases with stable development(SD),and 8 cases with progressive disease(PD). In the sorafenib group,3 cases were with CR,11 patients with PR,12 with SD,and 6 patients with PD. In the combination group,8 patients were with CR,20 patients with PR,2 patients with SD and 2 patients with PD,and the difference was significant between the two groups(χ2 = 14. 028,P = 0. 003). The median periods to tumor progression were 20 and 53 weeks in the sorafenib group and the combination group,and the difference was significant( χ2 = 14. 773,P = 0. 000). Conclusion For hepatocellular carcinoma patients without operation opportunity,sorafenib combined with TACE and PLCT can increase the tumor remission rate and prolong the periods to tumor progression in patients with hepatocellular carcinoma.

Objective:To investigate the possible role of miR-181d in regulating the multidrug resistance (MDR) of small cell lung cancer (SCLC) and its clinical significance. Methods: Quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and Western blot were used to investigate the differential expression of miR-181d and BCL2 from mRNA and protein levels in the chemo-sensitivity cell H69 and the chemo-resistance cell H69AR. The miR-181d expression in H69AR was then upregulated. More-over, CCK8 assay was employed to detect the sensitivities of the cells to chemotherapy drugs, such as ADM, DDP, and VP-16. Mean-while, the expression of miR-181d in the specimens of 87 cases with SCLC were detected using QRT-PCR. All patients received the chemotherapeutic regimen of EP (etoposide+cisplatin). Correlation of the miR-181d expression with clinicopathological features, prog-nosis, and survival time of the patients was studied. Results:miR-181d was downregulated in the SCLC multidrug-resistant cell line H69AR and chemo-resistant patients. Moreover, miR-181d was concurrent with the upregulation of BCL2 protein compared with the parental H69 cell line and chemo-sensitive patients (P<0.001). miR-181d expression in H69 cells resistant to chemotherapy drugs (ADM, DDP, and VP-16) was inhibited (P<0.01). Enforced miR-181d expression reduced the BCL2 protein level and sensitized H69AR cells to chemotherapy drugs (P<0.01). miR-181d expression was associated with tumor stage, sensitivity of chemotherapy, and survival time (all P<0.001). Patients with high miR-181d expression had longer overall survival and progress-free survival time com-pared with those with low miR-181d expression (P<0.001). Conclusion: miR-181d may play a role in the development of MDR in SCLC and may be a potential predictive factor for treatment efficacy.

Objective:To investigate the inhibitory effect of perillyl alcohol (PA) on the proliferation and invasion of tung cancer cell A549,and the influence of PA on tumor angiogenesis was studied.Methods:Different concentrations of PA and erlotinib were added into lung cancer cell A549,the inhibiting effect of drug group on lung cancer cell A549 was found by MTT assay.The inhibiting effect of PA on lung cancer cell A549 invasion was measured by Transwell assay.ROS changes of PA on lung cancer cell A549 was detected by fluorescent.Influence of PA on Caspase-3 activity of lung cancer cell A549 was measured by spectrophotometry,VEGF,HIF-1 α,COX-2 expression in lung cancer cell A549 was measured by Western blot,and the NF-κB activity of lung cancer cell A549 was measured by EMSA.Results:Compared with blank control group,cell growth inhibition rate of PA and erlotinib on lung cancer cell A549 was increasing with the increased concentrations (10,50,100 μ,g/ml),the difference was statistically significant (P＜ 0.05),the invasion ability of lung cancer cell A549 was decreased continuously,the difference was statistically significant (P＜0.05).The ROS level of lung cancer cell A549 had no obvious change with the increasing density of erlotinib,but obviously increased with the increasing concentrations of PA (10,50,100 μg/ml).With the increasing concentrations of PA,the expression of COX-2,VEGF and HIF-1α were continuously decreased.EMSA assay showed that NF-κB was continuously decreased with the increasing concentrations of PA.Conclusion:The antitumor mechanism of PA on lung cancer cell A549 might be related to increase the expression level of ROS and reduce the expression of activity of NF-κB,COX-2,VEGF and HIF-1α with angiogenesis signaling pathway.

Objective:To investigate the exression of miR-34a on lung cancer and normal lung tissues,and the effect and mechanism of miR-34a in lung cancer cell invasion and migration.Methods: qPCR was used to detect the expression of miR-34a on lung cancer.miR-34a-mimic and miR-34a-inhibitor were used to overexpress and knockdown miR-34a.qPCR was used to detect the effectiveness.Western blot was used to detect the expression of Snail after induced with miR-34a-mimic and miR-34a-inhibitor.Luciferase reporter gene was used to detect interaction between miR-34a and Snail.Transwell invasion assay was used to detect invasion ability after induced with miR-34a-mimic and miR-34a-inhibitor.Scratch assay was used to detect migration ability after induced with miR-34a-mimic and miR-34a-inhibitor.The expression of E-cadherin,Vimentin and Twist were detected by Western blot.Results: miR-34a expression was significantly reduced in lung cancer.With the stage of lung cancer progression,the expression of miR-34a reduced.With the differentiation of lung cancer progression,the expression of miR-34a decreased.Decreasing of miR-34a was associated with lung cancer lymph node metastasis.miR-34a-mimic and miR-34a-inhibitor could overexpress and knockdown miR-34a.miR-34a could regulate expression of Snail.Snail was the direct target of miR-34a;miR-34a could regulate the invasion ability of human lung carcinoma H1650 cells;miR-34a could regulate the migration of human lung carcinoma H1650 cells;miR-34a could regulate the expression of E-cadherin,Vimentin and Twist.Conclusion: miR-34a plays the role of tumor suppressor factor in lung cancer.miR-34a can regulate the invasion and migration ability of lung carcinoma H1650 cells by Snail induced EMT.

Perimenopausal syndrome is a common uncomfortable symptom in women during the perimenopausal period, with a high incidence, a long duration, and adverse effects on physical and psychological, patients bear a heavy burden of symptoms, and increase the risk of adverse events in the elderly stage, increase the social medical burden. With the development of sports rehabilitation research, more and more attention has been paid to the effect of exercise on human health. This paper reviews the studies on exercise rehabilitation in women with perimenopausal syndrome, including exercise forms, exercise intensity, exercise time and exercise effect, in order to provide basis for the relevant research and practice.

OBJECTIVETo investigate the role of homeobox gene A5 (HOXA5) in multidrug resistance of human small cell lung cancer (SCLC) cells and the possibility of using HOXA5 as the therapeutic targets for SCLC treatment.

METHODSWe examined HOXA5 mRNA and protein expressions in chemosensitive human SCLC cells (H69) and the multidrug-resistant SCLC cells (H69AR) using quantitative real-time PCR and immunoblotting. HOXA5 expression was then enhanced or suppressed by transfection of the cells with HOXA5 expression plasmids or small interference RNA (siRNA), and the chemosensitivity of transfected cells to cisplatin (DDP) and etoposide (VP-16) was evaluated using cell counting kit-8 (CCK8) assay.

RESULTSH69 cells showed a 8.99-fold higher expression of HOXA5 than H69AR cells. HOXA5 knockdown caused obvious reductions in the chemosensitivity of H69 cells to DDP and VP-16 with increased cells in G0/G1 phase; conversely, HOXA5 enhancement resulted in an increased sensitivity of H69AR cells to DDP and VP-16.

CONCLUSIONHOXA5 may play an important role in multidrug resistance of SCLC and can be a potential therapeutic target in clinical treatment of SCLC.

Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cisplatin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Etoposide ; pharmacology ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Immunoblotting ; Lung Neoplasms ; metabolism ; pathology ; Plasmids ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Real-Time Polymerase Chain Reaction ; Small Cell Lung Carcinoma ; metabolism ; pathology ; Transfection

OBJECTIVETo investigate the role of SALL4 in regulating multi-drug resistance in small cell lung cancer (SCLC), and to evaluate its clinical significance.

METHODSThe expression of SALL4 protein and gene was detected by Western blot and real-time PCR (RT-PCR) in both H69 and H69AR cell lines, respectively. SALL4 expression in H69AR was blocked by the siRNA, and then the drug-sensitivities of H69AR cell lines to chemotherapeutic drugs such as cisplatin, doxorubicin, and etoposide were evaluated by cell counting kit assay. SALL4 expression was also examined by immunohistochemistry, and correlated with patients' clinicopathological features and prognosis.

RESULTSThe expression of SALL4 was significantly increased in H69AR cells than in the H69 cells (P < 0.01). Down-regulation of SALL4 increased the drug-sensitivities of H69AR cells to chemotherapeutic drugs (P = 0.02). The expression of SALL4 was significantly increased in SCLC than in para-carcinoma tissues (P < 0.01). SALL4 expression correlated with clinical stage, chemosensitivity and overall survival (P < 0.05), but not with patients' age and gender.

CONCLUSIONSALL4 is involved in the regulation of multidrug resistance in SCLC; SALL4 may be a potential target gene to evaluate the chemosensitivity and clinical prognosis for SCLC.

Antineoplastic Agents ; pharmacology ; Cisplatin ; pharmacology ; Down-Regulation ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; physiology ; Drug Resistance, Neoplasm ; physiology ; Etoposide ; pharmacology ; Humans ; Lung Neoplasms ; drug therapy ; metabolism ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Small Cell Lung Carcinoma ; drug therapy ; metabolism ; Transcription Factors ; genetics ; physiology

Objective To investigate the expression and clinical significance of long non-coding RNA (lncRNA) RP11-629B11.4 in triple negative breast cancer (TNBC) patients.Methods The expression of lncRNA RP11-629B11.4 was detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) in TNBC tissues (n =45) and non triple negative breast cancer (N-TNBC,n =89) to analyze the relationship between the expression of lncRNA RP11-629B11.4 and the prognosis of patients.Results The expression of lncRNA RP1 1-629B11.4 in TNBC tissues was 7.805 ± 0.538,significantly higher than that in N-TNBC tissues (1.637 ± 0.409,t =21.460,P ＜ 0.001).The expression of lncRNA RP11-629B11.4 in the TNBC patients was related with histological grade (x2 =7.540,P =0.040),clinical stage (x2 =9.858,P =0.007),lymph node metastasis (x2 =4.388,P =0.036) and Ki-67 expression (x2 =7.872,P =0.005).In the N-TNBC group,there was no significant correlation between the expression of lncRNA RP11-629B11.4 and clinicopathological characteristics (all P ＞ 0.050).The progression free survival time of TNBC patients with higher expression of lncRNA RP11-629B11.4 was (15.90 ±2.76) months,shorter than that of patients with lower expression (26.62 ± 3.80) months,with a statistically significant difference (x2 =49.750,P ＜ 0.001).The overall survival time of TNBC patients with lower expression of lncRNA RP11-629B11.4 was (38.84 ±3.55) months,significantly longer than that of patients with higher expression [(24.69 ± 3.50) months],with a statistically significant difference (x2 =50.730,P ＜ 0.001).Cox regression model analysis showed that lymph node metastasis (HR =1.980,P =0.019),the expression of lncRNA RP11-629 B11.4 (HR =4.030,P ＜ 0.001) clinical stage (HR =2.670,P =0.008) and were independent prognostic factors in patients with TNBC.Conclusion The lncRNA RP11-629B11.4 is over-expressed in TNBC.lncRNA RP11-629B11.4 may be involved in the regulation of TNBC,and it may be used as a potential target for evaluating the prognosis of TNBC.