Paclitaxel (PTX)-loaded self-assembling nano-micelles (PTX/NMs) were prepared based on amphiphilic cholesterol-bearing γ-polyglutamic acid (γ-PGA-graft-CH). The properties of PTX/NMs in vitro and in vivo were investigated. The results indicated that PTX could be entrapped in γ-PGA-graft-CH NMs. PTX/NMs was characterized with a size of (343.5 ± 7.3) nm, drug loading content of 26.9% ± 0.8% and entrapment efficiency of 88.6% ± 1.7% at the optimized drug/carrier ratio of 1/10, and showed a pH-sensitive sustainable drug-release and less cytotoxicity in vitro. In vivo release and the pharmacokinetics study in mice showed that the elimination half-life ( t1/2 β ) and area under curve (AUC) of PTX/NMs were significantly higher than those of PTX/polyoxyethylene castor oil (PTX/PCO), and less clearance (CL) of PTX/NMs was also observed. PTX/NMs were distributed higher in liver and tumor than PTX/PCO, and showed a good tumor-inhibiting activity in tumor-bearing mice. This study would lay a foundation on the potential application of γ-PGA-graft-CH NMs were the antitumor drug-delivery.

To explore the intrinsic connection between activation of classical nuclear factor-κB (NF-κB) pathway and gefitinib resistance in human lung adenocarcinoma H1650 cells.

Objective: To investigate the efficacy and drug related adverse reactions of sorafenib and sunitinib as first-line tyrosine-kinase inhibitors (TKIs) for patients with metastatic renal cell carcinoma (mRCC) and analyze the clinical prognostic factor for survival. Methods: The data of 271 patients with metastatic renal cell carcinoma who had complete clinicopathological data were retrospectively analyzed, including 174 cases in sorafenib group and 97 cases in sunitinib group, to access patients' overall survival (OS) and progression-free survival (PFS). Prognostic values of all characteristics were determined by using univariate and multivariate Cox regression models. Results: The objective response rates (ORR) of the sorafenib and sunitinib groups were 14.9% and 19.6%, respectively, and the disease control rates (DCR) were 85.1% and 88.6%, respectively. No significant difference was found between the sorafenib and sunitinib group in ORR (P=0.325) or DCR (P=0.408). The most common grade 3 to 4 adverse events in the sorafenib group were hand-foot syndrome (6.7%), diarrhea (2.3%), and rash (2.3%). The most common grade 3 to 4 adverse events in the sunitinib group were neutropenia (6.2%), hand-foot syndrome (6.2%), and thrombocytopenia (4.6%). During the follow-up, 97 cases death occurred and 81 cases disease progression occurred in sorafenib group. The median PFS was 12 months (95% CI: 9-15 months), and the median OS was 25 months (95% CI: 21-29 months) in sorafenib group. While 74 cases death occurred and 40 cases disease progression occurred in sunitinib group, the median PFS was 12 months (95% CI: 10-12 months) and the median OS was 23 months (95% CI: 20-32 months) in sunitinib group. No significant difference was found between the sorafenib and the sunitinib group in PFS (P=0.771) or OS (P=0.548). Multivariate analysis showed Fuhrman grades (HR=1.358, 95%CI: 1.004-1.835), number of metastatic sites (HR=1.550, 95%CI: 1.143-2.101) and MSKCC risk grade (Intermediate risk group: HR=1.621, 95%CI: 1.117-2.232; Poor risk group: HR=2.890, 95%CI: 1.942-4.298) were independent prognostic factors for PFS. Fuhrman grades (HR=2.135, 95%CI: 1.533-2.974), number of metastatic sites (HR=1.774, 95%CI: 1.279-2.461) and MSKCC risk grade (Intermediate risk group: HR=1.415, 95%CI: 1.002-1.998; Poor risk group: HR=3.161, 95%CI: 2.065-4.838) were independent prognostic factors for OS. Conclusions: The results of this study indicate that sorafenib and sunitinib are both effective as the first-line TKIs for mRCC patients and sorafenib has comparable efficacy to sunitinib. But they have differences in the incidence of adverse effects. Fuhrman grades, number of metastatic sites and MSKCC risk grade are independent prognostic factors for mRCC patients.

Objective: To explore new multidrug resistant genes of pancreatic cancer by establishment and characterization of chemo-resistant cell lines. Methods: The cisplatin-resistant cell line JF305/CDDP and the gemcitabine-resistant cell line PANC-1/GEM were induced by high-dose intermittent treatment. CCK-8 assay was used to detect the 50% inhibiting concentration (IC(50)), drug resistance index (R), cross-resistance, and growth difference of different cells. The changes of cell cycle and migration ability of drug-resistant cells were determined by flow cytometry and transwell assay, respectively. And then real-time fluorescence quantitative PCR was used to detect the expression of multidrug resistance-related genes. Results: The drug resistance indexes of JF305/CDDP and PANC-1/GEM were 15.3 and 27.31, respectively, and there was cross-resistance. Compared with the parental cells, the proliferation rate of JF305/CDDP was decreased by 40% on the fourth day (P<0.05); the proportion of S phase was decreased from (45±2)% to (30±2)% (P<0.05), and the migration ability was enhanced from (32 ±1) cells per field to (158±5) cells per field (P<0.01). The expression of multidrug resistance-related genes MRP2, MDR1, LRP and MSX2 was increased in JF305/CDDP cells (P<0.05). Knockdown of MSX2 in JF305 cells reduced the expression of MRP2, whereas overexpression of MSX2 in PANC-1 cells upregulated MRP2 level (P<0.05). Conclusions: Two stable multidrug resistant cell lines of pancreatic cancer, JF305/CDDP and PANC-1/GEM, were successfully established. MSX2 might be a new drug resistance related gene in pancreatic cancer cells by up-regulation of MRP2 expression.

Objective:To investigate the mechanism between epithelial-mesenchymal transition (EMT) and cisplatin induced resistant cell subline and the malignant biological characteristics, to explore EMT in human hep-2 laryngeal resistant cells. Method:Using cisplatin-resistant cells (hep-2/CDDP) and non-resistant cells (hep-2) established in our previous study; the invasion and migration biological behaviors were detected by transwell and scratch assay; the expressions of E-cadherin, Zo-1, Snail, Slug, Twist1, Vimentinon in the mRNA level were detected by RT-qPCR and the protein level by Western blot. Result:Transwell and scratch assay show the invasion and migration behaviors were increased in hep-2/CDDP cells (P<0.05), the epithelial marker E-cadherin and Zo-1 were downregulated in hep-2/CDDP cells (all P<0.05), transcription factor Snail, Slug were upregulated in mRNA and protein level (all P<0.01) while Twist1 had no significant changed in protein level (P>0.05), the expression of mesenchymal marker Vimentin was also increased in mRNA and protein levels in cisplatin resistant cells (P<0.01). It was confirmed that the hep-2/CDDP cells possessed EMT phenotypes. Conclusion:The cisplatin resistant laryngeal cancer cells perform higherinvasion and migration biological behaviors,and the mechanisms of increased ability of invasion and migration induced by cisplatin was associated to eEMT, study on signal path related to EMT may overcome cisplatin resistance and reduce invasion and migration behaviors.

Objective:To study the relationship between transcription factor Snail and the sensitivity of cisplatin on human laryngeal resistant cancer cells.Method:siRNA interference of Snail was transfected by small RNA interference technology. The interference efficiency on mRNA level were detected by RT-qPCR assay; the expression of Snail protein level was assessed by immunofluorescence. The inhibition ratio of different cisplatin concentration (0, 1, 2, 4, 8, 16 μg/ml) was detected by CCK-8 assay; the protein level of Snail, E-cadherin, MDR1were detected by Western blot assay.Result:RT-qPCR assay show the expression of Snail on mRNA level was decreased to (67.85±9.50)% after transfection in Hep-2/CDDP cell(P<0.05). Immunofluorescence show fluorescence intensity of si-Hep-2/CDDP group was reduced both in nucleus and cytoplasm; CCK-8 assay show the inhibitory ratio of transfected group was increased compared to negative control and Hep-2/CDDP group in different cisplatin concentration (0, 1, 2, 4, 8, 16 μg/ml) (P<0.05). Western blot assay show the protein expression of Snail and MDR1 were down-regulated in transfected Hep-2/CDDP cells (allP<0.05), while epithelial marker E-cadherin was up-regulated in protein level (P<0.05).Conclusion:Small interference of transcription factor Snail could increase the expression of E-cadherin while decrease the expression of MDR1, and it was confirmed that interference Snail contribute to enhanced cisplatin sensitivity on human laryngeal resistant cancer cells.

Objective:To establish an subcutaneous xenotransplanted tumor model of papillary thyroid carcinoma (PTC) and investigate the role of metformin in apoptosis of PTC.Method:Model rats were randomly divided into four groups: control group, Met group and Met+DM group. The tumor volumes were recorded each week. Flow cytometry was used to detect the apoptosis rate of tumor. Immunohistochemistry was used to detect CyclinD1 and the cellular proliferative activity index PCNA and Ki-67.Result:Compared to the control group,there were a significant decrease in tumor volume and antitumor effect in Met and Met+DM groups. The apoptosis rate increased in Met and Met+DM groups. While compared with the control group, the expressions of PCNA,CyclinD1 and Ki-67 significantly decreased in Met and Met+DM groups. There was no difference between Met and Met+DM group.Conclusion:The effect of Metformin on inhibiting tumor growth were related with the imbalance of cell proliferation and apoptosis.

To investigate the clinical efficacy of stereotactic radiation therapy combined with temozolomide on recurrent glioma.
 Methods: A total of 36 patients with recurrent glioma were retrospectively analyzed and divided into a control group (n=12), who received stereotactic radiation therapy, and an experimental group (n=24), who received stereotactic radiation therapy plus temozolomide. The clinical efficacy and adverse reactions for the 2 groups were compared.
 Results: Total effective rate and local control rate for clinical treatment were 66.67% and 93.94%, respectively. Late adverse reaction was not observed. The effective rate and local control rate in the experimental group were 77.27% and 95.45%, which were slight higher than those in the control group, with no statistical significance (P>0.05). The 0.5-, 1-, 2-, 3-year follow-up total survival rates were 90.91%, 63.64%, 42.42%, and 15.15%, respectively. The 0.5-, 1-, 2-, 3-year follow-up survival rates in the experimental group were 95.45%, 72.72%, 54.54% and 22.73%, respectively, while those in the control group were 81.82%, 45.45%, 18.18%, and 0%, respectively. Survival analysis showed the survival time for the experimental group was significantly longer than that of the control group (30.00 months vs 14.00 months, P=0.010).
 Conclusion: Stereotactic radiation therapy combined with temozolomide for recurrent glioma is effective, and it has positive effect on improving the clinical efficacy and survival rate for the patients.

Objective:The aim of this study is to investigate the inhibitory effect and mechanism of tanshinone ⅡA combined with cisplatin on tumor Fadu cells in pharyngeal squamous cell carcinoma. Method:Cytotoxicity was determined by CCK8 assay. Flow cytometry was used to detect apoptosis and cell cycle distribution. Western blotting was used to assess the protein expression of related signaling proteins. Result:Compared with the two single drug groups treated with Tan ⅡA and DDP respectively, the combination group showed significantly higher anti-proliferative rate (P<0.01), arrested cell cycle at S phase, and resulted in observably higher apoptotic cell fractions in human hypopharyngeal squamous cell carcinomas Fadu cells; Western blotting showed that the protein expression of cleaved caspase 3 and cleaved PARP increased ,while survivin significantly decreased in the cells treated with the combination of tanshinone ⅡA and cisplatin. Conclusion:Tanshinone ⅡA potentiates the efficacy of Cisplatin in Fadu cells, which may be attributed to the downregulation of survivin protein expression.

Angiogenesis is an important process in the development of tumor. PD 0332991, a cell cycle inhibitor, can specifically inhibit CD4/6 phosphorylation and cell cycle progression. In xeongraft mice models, PD 0332991 treated mice had significantly decreased angiogenesis and vascular density compared with the control group, but the mechanism remains unknown. The purpose of this study is to investigate the role and molecular mechanism of PD 0332991 on vascular endothelial cells.

To explore the efficacy of sorafenib combined with chemotherapy and donor lymphocyte infusion (DLI) in patients with FLT3-positive acute myeloid leukemia (AML) relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Of the 14 patients relapsed after allo-HSCT, 9 achieved complete remission after salvage therapy of sorafenib combined with chemotherapy and DLI, 6 with complete molecular remission, 2 with partial remission, and 3 with no response. With a median follow up of 220 (range, 30-1 782) days after post-transplantation relapse, 7 patients were still alive and 7 died. Salvage therapy of sorafenib combined with chemotherapy and DLI shows a decent therapeutic effect for FLT3-positive AML relapsed after allo-HSCT.

Objective: To explore the effect of c-fos on multidrug resistance of laryngeal cancer TU177 cells. Method: Increasing drug concentration gradient is adopted to establish the stability of the laryngeal cancer drug resistance in cell line; RT-PCR and Western blot were used to detect difference of the c-fos between TU177 and TU177/VCR cells; plasmids with human c-fos knockdown or over expression were transfected into TU177/VCR and TU177 cells respectively, and the effects of different treatment on cell proliferation were investigated with MTT. Results: The drug resistance of TU177/VCR cells was 26.25-fold in vincristine (VCR), 7.33-fold in Paclitaxel (TAX), 2.41 in cisplatin (DDP), and 5.50 in 5-fluorouracil (5-FU), comparing with TU177( P<0.05). The TU177/VCR cells had significantly higher c-fos expression compared to TU177 cells( P<0.05). The results showed that the IC(50) values of 5-FU for the NC group and c-fos shRNA group were (306.2±6.3)μmol/L and (81.3±3.9)μmol/L, respectively, which was decreased by 73% in the c-fos shRNA group compared to that in the NC group (P<0.05). Similarly, the results showed that the IC(50) values for 5-FU were (55.3±9.4) μmol/L in NC group and (288.1±7.3)μmol/L in c-fos WT group, which was increased 5.21-fold in c-fos WT cells. Conclusion: C-fos plays important role in multidrug resistance of larynx cancer cell TU177/VCR, and might become a new molecular target for laryngeal cancer treatment.

To induce cisplatin-resistant cervical squamous carcinoma cell line and investigate the drug resistant mechanisms and adenovirus trans-gene therapeutical treatment.

Objective: To assess value of immediate postoperative intravesical instillation of pirarubicin after transurethral resection (TURBT)of non-muscle invasive bladder cancer. Methods: 484 patients diagnosed with non-muscle-invasive bladder cancer admitted to the Second Affiliated Hospital of Kunming Medical University were divided into two groups after transurethral resection of bladder tumor. 285 patients received postoperative intravesical instillation of pirarubicin within 6 hours after the surgery, 199 patients received first instillation of pirarubicin at 10 days after the surgery, after that, all the patients received routine bladder perfusion chemotherapy. Patients who received intravesical instillation of pirarubicin within 6 hours were defined as immediate intravesical instillation group and the other patients as the control group. Based on the European Organisation for Research and Treatment of Cancer risk tables, scores of recurrence and progression of patients were calculated and then stratified into risk groups accordingly. Recurrence and progression rates of the immediate intravesical instillation group were analyzed and then compared with the corresponding reference of the risk tables. Results: The 1-year and 5-year recurrence rate of patients with EORTC table scoring 0 in the immediate intravesical instillation group were significantly lower than that of the EORTC reference group (5.3% and 14.0% vs 15.0% and 31.0%, P<0.05). 1-year recurrence free rate between the immediate intravesical instillation group and the control group in patients scoring 1-4 was significantly different (81.3% vs 76.7%, P=0.014). However, 1-year recurrence free rate of the immediate intravesical instillation group was comparable with that of the control group in patients scoring 5-9, 10-17(P>0.05), which is quite close to the EORTC reference. The probability rates of 1-year and 5-year progression of the 285 patients who received immediate intravesical instillation group did not show significant difference with the EORTC reference. On multivariate analysis, previous recurrence, tumor grade G2-3, tumor multiplicity, delay of immediate intravesical instillation were independent risk factors of recurrence(P<0.05). Conclusions: With the help of EORTC recurrence risk table stratifying the patients into different risk groups, our study showed that delay of immediate postoperative intravesical instillation of chemotherapy after TURBT was an independent risk factor of post-surgery recurrence of tumor. Moreover, patients with EORTC scoring 1-4 might obtain greatest benefits.

To explore the feasibility, safety and clinical effect of mid-frequency transcutaneous electrical acupoint stimulation (TEAS) combined with oral tamoxifen (TAM) in the treatment of oligoasthenozoospermia.

To explore the apoptosis-inducing effect of the Chinese medicinal compound CFF-1 on prostate cancer cells and its related molecular mechanisms.

Objective To investigate the safety of a 60-minute rituximab rapid infusion protocol in the maintenance therapy for Chinese B-cell lymphoma patients (including the elderly) and to discuss the feasibility of rituximab treatment in outpatient departments or daily wards. Methods This prospective study enrolled 820 patients diagnosed with B cell lymphoma in the Department of Hematology of Peking Union Medical College Hospital from February 2015 to July 2016. From the second chemotherapy cycle,rituximab was infused within 60 minutes (100 mg/h over the first 15 minutes and the remaining dose given over 45 minutes, there was no maximum infusion rate,and 700 mg/h was acceptable),and the adverse reactions were recorded. Comparison was done between patients<65 years and≥65 years. Results The overall adverse reaction rate was 4.20% and no grade 4 or higher adverse reactions were recorded. The adverse reaction rate in the elderly patients was not significantly elevated. Conclusion For Chinese patients (including the elderly) with B cell lymphoma,the 60-minute rapid infusion of rituximab (beyond the first cycle) is a safe treatment option with low adverse reaction rate.

To explore the effect of the AXL expression on the chemosensitivity of prostate cancer PC-3 and DU145 cells to docetaxel and possible mechanisms.

Based on the anticancer mechanism of biological alkylating agent, we designed and synthesized two alpha pinene derivatives:(1R,5S)-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)methyl benzenesulfonate and (1R,5S)-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)methyl 4-methylbenzenesulfonate, of which structures were confirmed by ¹H-NMR, HPLC and MS date. These two compounds showed a good inhibition of tumor cells' proliferation. Further, the computer siuulation of molecular docking and metabolic kinetics indicated that these two copounds may have stable molecular complexation with protein CDK2, which closely related to the cell cycle.