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Objective@#To investigate the effect of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) on the mitochondrial mass in rat adrenal pheochromocytoma (PC12) cells and the potential mechanisms.@*Methods@#Highly differentiated PC12 cells were divided into control, 1, 10 or 20 μmol/L PBDE-47-treated groups and cultured for 24 h. Transmission electron microscopy was employed to observe the changes in mitochondrial morphology and quantity in PC12 cells. Flow cytometry was used to measure the fluorescence intensity of Nonyl Acridine Orange (NAO) , a fluorescent indicator of mitochondrial membrane cardiolipin, to reflect mitochondria mass. Western blotting was used to determine the expression levels of Mitofusion 1 (Mfn1) and Fission 1 (Fis1) proteins. To further explore the role of abnormal mitochondrial fusion and fission in PBDE-47-induced mitochondrial mass changes, PC12 cells were divided into control group, 5 μmol/L M1 treatment group, 20 μmol/L PBDE-47 treatment group and 5 μmol/L M1+20 μmol/L PBDE-47 combined treatment group and cultured for 24 h, then the fluorescence intensity of NAO and expression levels of Mfn1 and Fis1 proteins were detected.@*Results@#The control group showed numerous mitochondria with normal morphology, while the number of mitochondria decreased after PBDE-47 treatment. Especially, the disappeared cristae, swelling and vacuoles of mitochondria and decreased fluorescence intensity of NAO (P<0.05) were observed in 10 and 20 μmol/L PBDE-47-treated groups. Meanwhile, the expression levels of Mfn1 and Fis1 proteins in the 10 and 20 μmol/L PBDE-47-treated groups were significantly decreased compared with control group (P<0.05) . However, 5 μmol/L M1 co-treatment with 20 μmol/L PBDE-47 significantly increased the levels of Mfn1 and Fis1 proteins and fluorescence intensity of NAO compared with the 20 μmol/L PBDE-47 group (P<0.05) .@*Conclusion@#PBDE-47 can inhibit the mitochondrial fusion and fission process, thus leading to damage of mitochondria mass in PC12 cells.
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Objective To compare and analyze MRI characteristics of medical patellofemoral ligament(MPFL) injury patterns in adolescents and adults after acute lateral patellar dislocation.Methods MR images of 42 adolescents and 45 adults after acute lateral patellar dislocation were retrospectively reviewed.Routine MR scanning was performed in axial,sagittal and coronal planes,including T1 WI,T2 WI and fat saturation sequence.The x2-tests were performed to analyze the MPFL injury patterns between adolescent group and adult group.Results The prevalence rate of MPFL injury was 97.6％ (41/42) in adolescent group after acute lateral patellar dislocation,including 57.1％ (24/42) of complete tear and 40.5％ (17/42) of partial tear.The prevalence rate of MPFL injury was 100.0％ (45/45) in adult group,including 64.4％ (29/45) of complete tear and 35.6％ (16/45) of partial tear.There were no statistical difference between adolescents and adults in prevalence rate of MPFL injury,complete MPFL tear,partial MPFL tear (x2 =1.084,0.486,0.223 ; P ＞ 0.05).The prevalence rate of MPFL injury at femoral attachment,patellar attachment and midsubstance were 31.0％ (13/42),78.6％ (33/42) and 26.2％ (11/42) respectively in adolescent group,whereas they were 64.4％ (29/45),40.0％ (18/45) and 15.6％ (7/45) respectively in adult group.It occurred at multiple sites in 33.3％ (14/42) of adolescents,and in 15.6％ (7/45) of adults.There were significant differences between adolescents and adults in the prevalence rate of MPFL tear at femoral attachments and patellar attachments (x2 =9.759,13.324 ; P ＜ 0.05),but there was no statistical difference at its midsubstance (x2 =1.497,P ＞ 0.05).Although not statistically significant (x2 =3.749,P ＞ 0.05),MPFL tear at multiple locations were seen more in adolescents than in adults (33.3％ vs.15.6％).Conclusion The injury degree and distribution of MPFL are similar in adolescents and adults after acute lateral patellar dislocation,but there is significant difference in the site of MPFL injury distribution between adolescents and adults.MPFL is most easily injured at femoral attachment,secondly at patellar attachment in adults,while MPFL is most easily injured at patellar attachment,secondly at femoral attachment in adolescents.Adolescents are more likely to have multiple-site MPFL injury than adults.
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Objective To evaluate the clinical efficacy of Qingrehuashi herbal formula combined with high intensity focused ul-trasound(HIFU ) in the treatment of advanced pancreatic cancer .Methods 86 patients with pancreatic cancer (22 case of III stage and 64 case of IV stage) were included in this study .18 cases were performed the HIFU therapy for 2-3 times .Other 68 cases re-ceived once HIFU therapy ,among 53 cases of liver metastasis ,8 cases were simultaneously conducted HIFU ablation therapy on liv-er metastasis .The patients were given Chinese medicines dominated by Qingrehuashi before and after HIFU therapy and during fol-low up period .Results The single evaluation on HIFU irradiation cases after 1 month:complete remision(CR) in 0 case ,partial re-mission(PR) in 8 cases(9 .3% ) ,stable disease(SD in 64 cases(74 .4% ) and progress disease(PD) in 14 cases(16 .3% ) .The median survival rate of 1 year and half a year was 52 .0% and 11 .4% .Among 73 cases of increased CA199 before treatment ,CA199 after treatment was decreased in 12 cases .Among 36 cases of increased CA242 before treatment ,CA242 after treatment was decreased in 15 cases .The effective rate of analgesic relief in all the cases was 70 .9% (62/86) .Conclusion The integrated therapy of Qingre-huashi herbal formula and HIFU is an effective method for treating advanced pancreatic cancer .
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Smoothened (SMO) is a member of sonic hedgehog homology (SHH) signaling pathway. It plays a key role as a bridge between patched-1 (PTCH-1) and Gli. Aberrant SHH expression can be detected in various malignant tissues, and the expression in pancreatic cancer stem cells is higher apparently. SHH signals are closely associated with self-duplication of cancer stem cells, formation of tumor vessels as well as matrixes. SMO antagonists such as cyclopamine, GDC-0449 and so on show potential to inhibit activity of SHH signaling, and arrest the growth as well as metastases of tumors. Recently, a few of SMO antagonists have been studied in phase I clinical trials and some are in phase II, meanwhile, phase I or II trials of SMO antagonists to treat pancreatic cancer are performed currently. As the classical SMO antagonist, cyclopamine is extracted from a medicinal plant. Perhaps researchers may be able to determine more effective SMO-targeting drugs from herbal medicines in the future.
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Objective To evaluate the analgesic efficacy and effect of high intensity focused ultrasound (HIFU) in the treatment of advanced pancreatic cancer.Methods128 patients with pancreatic cancer ( Ⅲ stage 41 case,Ⅳ stage 87 case) were treated by HIFU.According to some parameters,such as the clinical symptoms,imaging examinations and survival analysis to assess the efficacy of HIFU treatment.Results22.9％ patients’ serum Ca19-9 decreased.The cancer pain was relieved in 72.5％ patients.Coagulated-necrosis by CT/MRI examination was observed.PR,SD and PD of all were 11.7％,70.3％ and 18.0％ respectively.1-year survival rate was 16.7％ for all patients,and median survival time was 7.0 months.1-year survival rate and median survival time for Ⅲ stage group were 28.5％ and 9.0 months,that of 10.8％ and 6.0 months for Ⅳ stage group respectively.ConclusionHIFU may benefit to advanced pancreatic cancer patient by stabilizing tumors,relieving pain and prolonging life expectancy with less side effects.
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Objective: To investigate the effects of Qingyi Huaji (QYHJ) decoction, a compound traditional Chinese herbal medicine, on tumor inhibition rate and serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in nude mice with transplanted tumors of human pancreatic cancer. Methods: The tumor-bearing mice model was established by subcutaneously inoculating with xenografts of pancreatic cancer into the right armpit of 40 BALB/c nude mice. After successful modeling, the mice were randomly divided into untreated group (Arabic gum), capecitabine group, low-dose QYHJ decoction group (36 g/kg) and high-dose QYHJ decoction group (72 g/kg), with 10 mice in each group. Citrate buffer solution (containing 5% Arabic gum), capecitabine suspension and QYHJ decoction were administered to four groups by gavage respectively. After 5-week treatment, the concentrations of serum IL-6, IL-8 and TNF-alpha were examined by enzyme-linked immunosorbent assay (ELISA) using blood sample from eye socket. Then the mice were euthanized by cervical dislocation. Tumor weight and the tumor inhibition rate were calculated. Results: Tumor weight in the low-dose QYHJ decoction group decreased significantly as compared with the untreated group (P<0.05). Serum levels of IL-6 and TNF-alpha in low- and high-dose QYHJ groups were extremely significantly lower than those in the untreated group (P<0.01). Serum level of IL-8 in the low-dose QYHJ group was significantly lower than that in the untreated group (P<0.05). Correlation analysis showed that transplanted tumor weight of the mice was linearly positively correlated with serum levels of IL-6, IL-8 or TNF-alpha (P<0.01). Conclusion: Conventional dose of QYHJ decoction is effective in suppressing pancreatic carcinoma in nude mice. The mechanism may be related to down-regulation of serum cytokines such as IL-6, IL-8 and TNF-alpha.
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Objective: To investigate the effect of cinobufacini on proliferation, celly cycle distribution, invasion capability of MDA-MB-231 breast cancer cell line in vitro and possible mechanism. Methods: The effect of cinobufacini on cell growth was measured by CCK-8 reagent kit. Cell cycle distribution was determined by flow cytometry. The invasion capability in vitro was detected by Transwell chamber assay. The mRNA expressions of cell cycle related factors (cyclin) and p21 were tested by RT-PCR. Results: Cinobufacini inhibited proliferation of MDA-MB-231 cells. The half inhibition concentration (IC50) was 0.31 mg/mL. The inhibitory effect was timE-dependent (P<0.05). Cinobufacini significantly decreased invasion capability of MDA-MB-231 cells in vitro compared with control group (P<0.05). Cinobufacini induced S-phase arrest of MDA-MB-231 cells in a concentration-dependent manner (P<0.000 1). Cinobufacini down-regulated the expression levels of cyclin A1, cyclin D1, and cyclin E1, while up-regulated that of p21 in MDA-MB-231 cell line. However, there was no marked change in the expression of cyclin B1. Conclusion: Cinobufacini inhibits cell proliferation and influences the cell cycle distribution in vitro by regulating the expression of cyclin A1, cyclin D1, cyclin E1 and p21 in breast can-cer cells.
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OBJECTIVE: To observe the effects of ethanol extracts of Panax notoginseng on the tumor and the liver metastasis in experimental mice grafted with B16 melanoma. METHODS: B16 melanoma was transplanted in the spleen of C57BL/6 mice. The effects of different doses of ethanol extracts of Panax notoginseng on the inhibition rate of spleen tumors and the liver metastasis were observed respectively. RESULTS: The high-, medium-, and low-doses of the extracts and the interferon-alpha (IFN-alpha) can improve the quality of life of the experimental mice. The weights of spleen tumor were lower in the low- and medium-dose extracts-treated groups and the IFN-alpha-treated group than that in the normal saline (NS)-treated group (P<0.05 or P<0.01). The liver metastasis was less in the low- and medium-dose extracts-treated groups and the IFN-alpha-treated group than that in the NS-treated group (P<0.01). CONCLUSION: The ethanol extracts of Panax notoginseng can improve the quality of life of the experimental mice and inhibit the growth of tumor and the liver metastasis.
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Background and purpose:Advanced pancreatic cancer is characteristic of poor treatment eff icacy and short survival time. Gemcitabine is considered as front-line therapy for advanced pancreatic cancer. Gemcitabine combinations have shown a favorable impact on survival. We compared gemcitabine-based combination cheme therapy and gemcitabine(GEM) alone in patients with advanced pancreatic cancer through Meta analysis in phase Ⅲ clinical trials. Methods:MEDLINE and EMBASE searches were supplemented by information from trial registers of phase Ⅲ randomized controlled trials(RCTs) for GEM-based combination therapy and GEM alone for advanced pancreatic cancer. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available RCTs. The Meta-analysis involved 6-months and 1-year survival rate and objective remission rate(ORR) . Results:The Meta-analysis included 20 RCTs. The result of our Meta-analysis showed that there was signifi cant improvement in the GEM combination group with regard to the 1-year survival rate(RR:0.87,95%:(0.78,0.96) ,P=0.008) . The other result of our meta-analysis showed no signifi cant difference between two groups. Conclusion:GEM-based combination therapy may be effective with regard to the survival rate compared with GEM alone.
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To observe the effects of Shengmai Injection on enhancing efficacy and reducing toxicity of 5-fluorouracil (5-FU).
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<p><b>BACKGROUND</b>To evaluate and compare the effects and toxicity of the domestic product of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy and chemotherapy alone in the treatment of patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Two hundred patients with NSCLC in multicenter were randomly devided into trial group (150 cases) and control group (50 cases). Chemotherapy with CAP regimen was given to the patients. Meanwhile, rmhTNF injection of 4×10⁶U/m² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy cycle in the trial group. The control patients received chemotherapy alone. Twenty-one days were as a cycle, 2 cycles were given to each patient. The chemotherapeutic effects and toxicity were observed and compared between the two groups after the therapy.</p><p><b>RESULTS</b>of the 200 patients, 5 cases in the trial group and 3 cases in the control group were out of the trial because of economy. The other 192 cases (145 cases in the trial group and 47 cases in the control group) could be analyzed and evaluated the clinical effects and toxicity. The response rate of chemotherapy was 46.90% (68/145) in the trial group and 17.02% (8/47) in the control group respectively ( P =0.001). The KPS scores was 86.02±9.74 in the trial group, and 80.14±9.10 in the control group ( P =0.025). No significant difference of degree III+IV toxicity was observed between the two groups ( P > 0.05). The side effects related to rmhTNF included slight fever, cold-like symptoms, pain and red and swelling in the injection site. All of them were mild and didn't need any treatment and disappeared after the therapy. There were no severe abnormality of liver and kidney function and ECG in both groups.</p><p><b>CONCLUSIONS</b>The results demonstrate that the effects of domestic rmhTNF combined with chemotherapy are remarkably higher than that of chemotherapy alone in the treatment of NSCLC. rmhTNF can increase the sensitivity to chemotherapy and improve the quality of life of the patients with slight toxicity. Hence rmhTNF is worth expanding clinical use.</p>
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OBJECTIVE: To observe the correlation between serum level of TXB2, 6-Keto-PGF1alpha and liver metastasis. METHODS: The metastatic model was made by injection of W256 carcinosarcoma. Rats were randomly divided into two groups: rats with blood stasis group and control group. Rats in control group were given normal saline via abdominal cavity once a day. Rats in blood stasis group were injected adrenalin in the fourteenth day. Tumor size and liver metastasis were observed. Serum TXB2 and 6-Keto-PGF1alpha were tested by radioimmunoassay. RESULTS: Tumor size in rats with blood stasis was significantly smaller than that of the control group (P<0.01). Occurrence of liver metastasis in rats with blood stasis was significantly lower than that of the control group (P<0.01). The values of 6-Keto-PGF1alpha, TXB2, and TXB2/6-Keto-PGF1alpha were higher in the group with blood stasis. CONCLUSION: In the status of blood stasis, W256 carcinosarcoma grows slowly, and liver metastasis increases insignificantly, with the elevations of 6-Keto-PGF1alpha, TXB2 and TXB2/6-Keto-PGF1alpha.
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This paper explored the clinical thinking way in treating disease by integration of traditional Chinese and western medicine(ITCWM). In accordance with the challenge and problems the subject of ITCWM faced, the standard of diagnosis, treatment and evaluation of therapeutic response should be established. The combination of symptoms-differentiation with special prescription/drug for special disease to increase the accuracy of treatment is the developing direction for clinical medicine and ITCWM. Absorption and utilization of modern science and technique is the prerequisite for breaking through in ITCWM theory. The key of combining two different medical theories is to look for link joint.
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OBJECTIVE: To evaluate the treatment effect, quality of life and side-effect of transcatheter arterial chemoembolization (TACE) and traditional Chinese medicine (TCM) in treating metastatic liver cancer. METHODS: Thirty-nine cases of colon metastatic liver cancer were randomly divided into two groups. Both TACE and TCM were used in the treatment group, while only TACE was used in the control group. The drug used in TACE included floxuridine, pirarubicin, cisplatin, and the herbs for strengthening the spleen and regulating Qi were used in TCM. RESULTS: The response rate in the treatment group was 30% (45% including minor remission patients), and the median survival time was 18.6 months. While in the control group the response rate was 15.8% (36.8% including minor remission patients), and the median survival time was 14.3 months. The 1-, 2-, 3- year survival rates of treatment group and the control group were 70.2%, 40.3%, 13.0% and 68.7%, 29.5%, 10.3% respectively. There were fewer other organ metastases in the treatment group. The score from the EORTC quality of life questionnaire QLQ-C30 in treatment group was higher than that in the control group. CONCLUSION: Integration of TACE and TCM in treating colon metastatic liver cancer has better results.
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Purpose:To study the effect of the herbal decoction Qingyi Xiaoji Formula(QYXJ) on the proliferation of human pancreatic cancer cell line SW1990 in vivo and to explore the mechanism of its functions by means of cDNA microarray.Methods:Tumor-burdened nude mice were randomized into control group,5-FU group,and QYXJ groups at different dosages.After treatment,inhibiting rates of tumor growth were calculated.Tumor mRNA of the control group and the QYXJ group at moderate dose was extracted.The fluorescent cDNA probes were prepared,labeled with two different dyes Cy3 and Cy5,and then hybridized with cDNA microarray and scanned for fluorescent intensity.The genes with different expression were identified through the analysis of gene expression profile.Results:Inhibition rates of tumor growth in the QYXJ groups were 21.31%,38.16% and 29.09%,in the dose of 18 g/kg,36 g/kg,and 72 g/kg respectively.7 genes with reduced expression were identified,the functions of which were oncogene,protein translation and synthesis,DNA synthesis and repair,cell signal transduction,etc.Conclusions:QYXJ decoction may inhibit the proliferation of pancreatic cancer in vivo,possibly by blocking the action of an oncogene and its downstream signaling,or by regulation of protein synthesis in cancer cells.
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The stem cell hypothesis for cancer suggests that only a specific subset of cancer cells within each tumor is responsible for tumor initiation and propagation,termed cancer stem cells(CSCs),which have a character of self-renewal and multilineage differentiation,and responsible for the recurrence,metastasis and resistance to therapy.The CSC of pancreatic cancer were isolated and identified in 2007,and recent data has been reported to confirm the change of the related signal pathway,the relationship with metastasis,therapy resistance and the puzzle.This review article summarizes the latest advances with regard to the pancreatic cancer stem cells.
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Background and purpose:Huachansu has been widely used to treat cancer in China.But maximum tolerated dose(MTD) of huachansu is still not well defined.The purpose of this study was to conduct a Phase Ⅰ study to determine the MTD of huachansu in the treatment of patients with hepatocellular carcinoma,non-small cell lung or pancreatic cancer.Toxic profile and efficacy of huachansu were also assessed qualitatively.Methods:Huachansu was intravenously administered to patients with stage Ⅲ/Ⅳ hepatocellular carcinoma,non-small cell lung cancer,or pancreatic cancer.Each cycle consisted of daily huachansu for 14 days with an interval of 7 days between two cycles.2 or more cycles were delivered to the patients if no severe adverse event occurred.The planned dose escalation schedule for huachansu was as follows,10,20,40,60,90 and 120 ml/(m2?d).Results:Fifteen patients(3 at each level) have been recruited to the study(11 with hepatocellular carcinoma,2 with pancreatic cancer,and 2 with lung cancer).There were no dose limiting toxicities found after dose level 5.Among all these patients,the efficacy in 14 patients could be valued,in which,6 were SD(42.9%),8 were PD(57.1%).At dose level 1,there was one patient with hepatocellular carcinoma achieving a 20% reduction in tumor mass that lasted 11 months,6 of 15(42.9%) patients with stable disease and 8 of 15(57.1%) with progress disease after the treatment.Conclusions:To date,dose limiting toxicity has not been seen with doses up to eight times higher than that typically used before.Of interest, several patients had prolonged stable disease or minor tumor shrinkage.
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AIM: To observe the changes in tumor-weight-inhibiting rates,immunological function,liver and renal function and the blood cell in the peripheral blood after administration of Shengmai Injection combined with chemotherapeutic agent,Oxaliplatin. METHODS: Hepatoma 22 tumor bearing mice models were established and then divided randomly into five groups,including control group,Oxaliplatin group,Shengmai Injection(high,middle and low dose) combined with Oxaliplatin groups.Each group had 10 mice.The five groups were injected introperitoneally with same amount of 5% glucose injection,Oxaliplatin 6 mg/kg and Shengmai Injection(14 mL/kg,7 mL/kg and 3.5 mL/kg) plus Oxaliplatin 6 mg/kg respectively,once a day for 14 days. After that,mice in the five groups were all killed after being anesthetized and the tumor-weight-inhibiting rates and the index of immunological function,liver and renal function and the blood cell in the peripheral blood were observed. RESULTS: (1) The tumor-weight-inhibiting rates were higher in each Shengmai Injection plus Oxaliplatin group than that in the Oxaliplatin group (P