The present research was launched to investigate the effects of 12 annonaceous acetogenins (ACGs) on human hepatic carcinoma cell line SMMC-7721/ADR, and to find out their structure-activity relationship. SMMC-7721/ADR cells were treated with 12 ACGs including annosquamin A(1)，annosquamin B(2)，annotemoyin-1(3)，uvariamicin Ⅱ(4)，annosquacin D(5)，annosquacin B(6)，isodesacetyluvaricin(7)，uvarigrandin A(8)，squamostatin D(9)，squamostatin E(10)，squamostatin A(11)，and 12,15-cis-squamostatin A(12) for 24 h, and the different expression of the target gene NDUFV2 were detected by quantitative real-time PCR. All the tested compounds made the expression of the target gene NDUFV2 decreased on human hepatic carcinoma cell line SMMC-7721/ADR, of which the bistetrahydrofuran ACGs showed the best activity,which the non-adjacent bistetrahydrofuran ACGs displayed the worst activity.The ACGs with the reducing number of carbons between γ-unsaturated lactone and the close tetrahydrofuran (THF) ring are more potent. For bistetrahydrofuran ACGs with the same nucleus skeleton,they would be more active as more hydroxyls on aliphatic chain, which for the non-adjacent bistetrahydrofuran ACGs with less hydroxyls on aliphatic chain that would be more active. ACGs with 3 hydroxyls on aliphatic chain would be more active. ACGs with threo configuration are more active than erythro configurotion, and the compounds with cis THF ring seem to be superior to those of trans THF ring. Furthermore, the ACGs with the reducing number of carbons between terminal methyl and the close tetrahydrofuran (THF) ring are more potent.

Objective: To investigate the safety, efficacy and prognostic factors of S-1 versus capecitabine in patients with advanced breast cancer (ABC). Methods: From January 1, 2012 to December 31, 2014, 154 ABC patients with pathological diagnosis were separated into two groups: S-1 with or without the 3rd generation chemotherapy drug (group S-1) and capecitabine with or without the 3rd generation chemotherapy drug (Group capecitabine). The efficacy, side effects and prognostic factors were compared between the two groups. Results: There were 70 patients in group S-1 and 84 patients in group capecitabine. The objective response rates (ORR) were 31.4% (22/70) in group S-1 and 28.6% (24/84) in group capecitabine. The disease control rates (DCR) were 74.3% (52/70) and 83.3% (70/84), respectively. There were no significant differences in DCR and ORR between two groups (P>0.05). The DCR of patients treated with capecitabine monotherapy was significantly higher than that of S-1 monotherapy [94.4%(17/18) and 64.0%(16/25), P=0.028]. The median PFS was 7.5 and 8.9 months for the patients in the group S-1 and group capecitabine, with no statistically significant difference (P=0.423). The 1-year survival rates of group S-1 and group capecitabine were 81.4% and 66.7%, respectively, with no significant differences(P=0.020). Univariate analysis showed that ER and/or PR status (P=0.004), T stage (P=0.041), and molecular typing (P=0.046) were associated with PFS. Multivariate analysis showed ER and/or PR status (P=0.034) was an independent prognostic factor related with PFS. The incidence of hemoglobin reduction was 14.3% (10/70) and 36.9% (31/84) in the group S-1 and group capecitabine, and the differences were statistically significant (P=0.002). There was no significant difference in the incidence of leukopenia, neutropenia, thrombocytopenia and hand-foot syndrome between the two groups(P>0.05). Conclusions: S-1 and capecitabine are both effective for advanced breast cancer. Neither ORR nor DCR were significantly different between these two groups. The incidence of gastrointestinal reactions and thrombocytopenia of S-1 was slightly lower than that of capecitabine.

Objective: To investigate the effect of mesenchymal stem cells (MSCs) on apoptosis of breast cancer cell line MCF-7 induced by cisplatin (DDP), MSCs derived from breast cancer (BC-MSCs) or adjacent non-cancerous tissues (BN-MSCs) were isolated, cultured and identified. Methods: BC-MSCs and BN-MSCs were isolated and cultured by tissue adherent method. The differentiation potential of BC-MSCs was detected by osteogenic and adipogenic induction, and cell surface markers of BC-MSCs and BN-MSCs were evaluated by flow cytometry. MCF-7 cells were co-treated with DDP and conditioned medium (CM) collected from BC-MSCs and BN-MSCs after being cultured for 48 hours, respectively. Inhibition rate of cell proliferation was evaluated by MTT. Cell apoptosis and viability were detected by MUSE cell analyzer. Cytokines in MSC-CM were detected by Luminex liquid chip. Interleukin 6 (IL-6) mRNA expressions in MCF-7 cells with different treatment were detected by RT-PCR. Results: The morphology of BC-MSCs and BN-MSCs successfully isolated and cultured was uniform fibroblast-like clusters under the microscope. These cells expressed high levels of CD29 and CD44, but neither CD14 nor CD34 were detected. MSCs could also differentiate into osteoblasts and adipocytes after specific induction. After treatment with 2.5, 5, 10, 20, 40 and 80 μmol/L DDP, the inhibitory rates of proliferation of MCF-7 cells in DDP group were (17.33±2.00)%, (22.37±0.73)%, (30.77±1.23)%, (44.93±1.27)%, (62.03 ±1.97)% and (73.93±1.10)%, respectively. While the inhibitory rates of DDP+ BC-MSCs group were (8.27±0.63)%, (11.50±1.30)%, (20.57±0.93)%, (32.60 ±1.90)%, (52.27±0.73)% and (62.13±2.17)%, respectively. The inhibitory rates of DDP+ BN-MSCs group were (12.90±1.60)%, (16.53±2.87)%, (25.90±1.50)%, (39.40±2.40)%, (57.40±0.70)% and (69.03±1.07)%, respectively. The inhibitory rates of DDP+ BC-MSCs group were significantly lower than those of DDP group (P<0.05). The apoptotic rates of MCF-7 cells in DDP group, DDP+ BC-MSCs group and DDP+ BN-MSCs group were (47.77±1.98)%, (29.20±2.12)% and (37.92±2.21)%, respectively. The apoptotic rates of DDP group was significantly higher than that of DDP+ BC-MSCs group (P<0.05). The cell viabilities of MCF-7 in DDP group, DDP+ BC-MSCs group and DDP+ BN-MSCs group were 0.52±0.02, 0.72±0.02 and 0.64±0.02, respectively. The cell viability of DDP group was significantly lower than that of DDP+ BC-MSCs group (P<0.05). The result of Luminex liquid chip analysis showed that, the level of IL-6 in BC-MSCs group increased 2.50±0.68 fold when compared with BN-MSCs group (P<0.05). The relative expressions of IL-6 mRNA in DDP group and DDP+ BC-MSCs group were 1.02±0.10 and 7.58±0.55, respectively, with a statistically significant difference (P<0.01). The apoptotic rates of MCF-7 cells in DDP+ BC-MSCs group with or without IL-6 neutralizing antibody were (27.41±1.95)% and (42.45±2.87)%, respectively, with a statistically significant difference (P<0.05). The cell viabilities of MCF-7 cells in DDP+ BC-MSCs group with or without IL-6 neutralizing antibody were (72.40±2.60)% and (59.76±3.89)%, respectively, with a statistically significant difference (P<0.05). Conclusions: BC-MSCs and BN-MSCs have been isolated and cultured successfully. Compared with BN-MSCs, BC-MSCs could attenuate the effect of DDP on MCF-7 cells, evidently decrease the apoptosis and increase the proliferation and vitality in an IL-6 dependent manner.

In the study, we developed a novel formulation, CD123 mono-antibody (mAb) modified tanshinone ⅡA loaded immunoliposome (CD123-TanⅡA-ILP) to achieve the targeted drug delivery for leukemia cells. Orthogonal test was used to optimize liposome preparation, and the TanⅡA-loaded PEGylated liposomes (TanⅡA-LP) of S100PC-Chol-(mPEG2000-DSPE)-TanⅡA at 19∶5∶1∶1 molar ratio were prepared by the thin film hydration-probe ultrasonic method. A post-insertion method was applied to prepare CD123-TanⅡA-ILP via thiolated mAb conjugated to the terminal of maleimide-PEG2000-DSPE. The cellular uptake assay was measured by flow cytometry, and the inhibitory effect of CD123-TanⅡA-ILP on NB4 cells proliferation was tested by using MTT assay. The results of cellular uptake assay showed that CD123-ILP could significantly increase the drug uptake of NB4 cells as compared with free drugs and LP. The IC₅₀ values at 48 h incubation were 20.87, 11.71, 7.17 μmol•L⁻¹ respectively for TanⅡA，TanⅡA-LP and CD123-TanⅡA-ILP. CD123-ILP demonstrated a potential and promising targeted drug delivery strategy for acute myelogenous leukemia (AML) treatment.

The antimicrobial activity and cytotoxicity in vitro of the fermentation broth of 10 endophytic strains isolated from Lycium barbarum were determined to screen high activity endophytic strains. Sequences analysis of ITS and 16S rDNA was used for molecular identification of the strains. The results showed that 5 endophytic fungi had no inhibitory activity against the tested pathogens. Endophytic actinomycete strain AL6 had a certain inhibitory effect on 3 kinds of pathogenic fungi, and strain AL5 only had strong inhibitory activity against Staphylococcus aureus. However, the anti-tumor activity of endophytic fungi was significantly higher than that of actinomycetes. Four endophytic fungi strains exhibited the growth inhibition rate of above 50% against at least one of the tested tumor cells when the concentration of fermentation broth was 0.2 g•L⁻¹. Sequences analysis showed that 5 endophytic fungi strains belonged to genus Aspergillus, Penicillium and Emericella, and the 5 endophytic actinomycetes strains belonged to genus Aspergillus, Penicillium and Emericella. Aspergillus strain FL1 had stronger inhibitory activity against A549 and HeLa cells, and the IC₅₀ values were 0.022，0.028 g•L⁻¹, respectively, which was worthy of further study.

Anti-cancer chemotherapy may cause skin-toxicity reactions. Different types of cooling packages affect chemotherapy-induced skin toxicity reactions differently.

Objective: In order to improve the drug's solubility, dissolution and bioavailability, RG-β-CD, RG-γ-CD and RG-Hp-β-CD were prepared by co-crystallization between Regorafenib (RG) and β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD) and Hydroxypropyl-β-cyclodextrin (Hp-β-CD). Methods: Three inclusion complexes were prepared by recrystallization and solvent evaporation methods and characterized by fourier transform infrared spectroscopy (FT-IR), thermal analysis (TG), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), 1H nuclear magnetic resonance (1H-NMR), nuclear overhauser effect spectroscopy (NOESY). In vivo experiments, tumor suppression assay were made with SW620 colon cancer cell. Results: The ability of solubility and dissolution were improved after inclusion with three kinds of cyclodextrins. The regorafenib-β-cyclodextrin inclusionis proved to have the best stability. The less enhanced was regorafenib-γ-cycl-odextrin inclusion. The best dissolution of regorafenib-β-cyclodextrin inclusion complex was to bring as the tumor suppression assay, the result shows that regorafenib inclusion with β-cyclodextrin is better than regorafenib itself. Conclusion: The bioavailability of regorafenib by inclusion with cyclodextrin can enhance due to the solubility enhancement of RG, which can provide an effective method for improving solubility and dissolution of insoluble drug in clinical medication.

Objective: To synthesize 5-fluorouracil-nicotinamide (5-FU-NCT) cocrystal and to investigate its physicochemical and biological properties. Methods: The cocrystal of 5-Fu-NCT was prepared through the cooling technology. PXRD, NMR, FTIR and DSC were used to characterize the structure of 5-FU-NCT cocrystal. Solubility was measured by HPLC method. Drug resistant human liver cancer BEL-7402/5-FU cells were treated with 5-FU-NCT cocrystal, the inhibition effect was tested by MTT and HE staining, and cancer cell migration was determined by scratch test. Results: According to PXRD, NMR, FTIR and DSC results, the cocrystal of 5-Fu-NCT had been synthesized successfully. The characteristic diffraction peaks (2θ/°) of the cocrystal were 16.4, 20.4, 22.3, 27.9 and 30.1. The solubility of 5-FU-NCT was 13.5 g/L as measured by HPLC. The antitumor activity tests showed that 5-FU-NCT cocrystal enhanced anticancer effect of 5-FU, and the IC50 of 5-FU and 5-FU-NCT was 129.6 μg/mL and 42.6 μg/mL, respectively. Conclusion: 5-Fu-NCT cocrystal have been synthesized successfully through the cooling technology and it shows an enhanced anticancer effect in comparison to 5-FU on BEL-7402/5-FU cells.

Surgical resection is the best choice for early lung cancer, but the prognosis of early postoperative lung cancer is still very different, whether or not to apply adjuvant chemotherapy is controversial. This study examines the role of postoperative adjuvant chemotherapy in patients with stage I non-small cell lung cancer (NSCLC), particularly in high-risk groups.

Albumin-bound paclitaxel is a novel paclitaxel formulation formed by the combination of paclitaxel and human serum albumin (HSA) to improve the efficacy of paclitaxel and reduce its adverse reactions. The aim of this retrospective study is to observe the efficacy and safety of albumin-bound paclitaxel-based therapy in the treatment of lung cancer.

Objective: To investigate the effect of curcumin on the apoptosis and autophagy of human gastric cancer cells with different degree of differentiation. Methods: Gastric cancer cell lines BGC-823 and MKN-28 were treated with curcumin at different concentrations. The effect of curcumin on cell proliferation was measured by MTT assay. Apoptosis was assessed by flow cytometry. Autophagy status was analyzed by acridine orange staining. The expression levels of apoptotic and autophagy-related proteins were detected by Western blot. Results: The cell viability of BGC-823 and MKN-28 was inhibited by curcumin in a time- and dose-dependent manner. At 48 h after treatment, the IC(50) value of BGC-823 (15.18 μmol/L) was close to that of MKN-28 (15.84 μmol/L), and the difference was not statistically significant (P=0.513). Meanwhile, flow cytometry showed that curcumin induced the apoptosis of gastric cancer cells in a dose-dependent manner. Western blot results showed that the expression of pro-apoptotic proteins bax, active-caspase-3 and active-caspase-9 was significantly increased in BGC-823 and MKN-28 cells, whereas that of the anti-apoptotic protein bcl-2 was strikingly reduced. In addition, the formation of acidic vesicular organelles in cytoplasm, conversion of LC3-Ⅰ to LC3-Ⅱ and increased levels of autophagy-related proteins Beclin1, Atg7 and Atg5-Atg12 were observed in curcumin-treated cells. Moreover, activation of PI3K/Akt/mTOR signaling pathway was also significantly suppressed after curcumin treatment. Blocking autophagy by adding the autophagy inhibitor 3-methyladenine (3-MA) significantly promoted the apoptotic cell death induced by curcumin. Conclusions: Curcumin induces apoptosis and protective autophagy in human gastric cancer cells in vitro. Curcumin combined with autophagy inhibitor may provide a more effective strategy for its clinical application.

As the third confirmed gaseous transmitters, hydrogen sulfide was found to play a vital role in the eternal milieu both physiologically and pathologically. What's intriguing is that, there exists a debate about the role of hydrogen sulfide in the pathogenesis of cancer, especially colorectal cancer. In this manuscript, progress of the effect of low and high dose hydrogen sulfide on the tumorigenesis of colorectal cancer and research on the antitumor new drugs stemmed from the function of hydrogen sulfide is summarized. Recently, the "bell-shape" model of the action of hydrogen sulfide illustrated that hydrogen sulfide was able to promote the progression of tumor in low dose and inhibit the progression of tumor in high dose. Based on these results, both hydrogen sulfide synthesis inhibitors and hydrogen sulfide donors(chimeras with NSAIDs) have been widely studied as potential anti-tumor novel drugs. According to the actual results of present studies, hydrogen sulfide synthesis inhibitors featured by aminooxyacetic acid (AOA) is more promising as a novel kind of drug. The future research based on the relationship between hydrogen sulfide and rectal cancer may bring insights into the development of novel anti-tumor drugs, thus producing tremendous potential clinical value.

To investigate the adverse effects of high-dose methotrexate (HDMTX) therapy, and to provide a theoretical basis for optimizing clinical treatment.

To investigate effects of miR-503 on cisplatin sensitivity in BEL-7402 cells by targeting of bcl-2.
 Methods: MiR-503 and bcl-2 mRNA expression levels in hepatocellular carcinoma cells were measured by real-time quantitative (qRT)-PCR; Bcl-protein level was detected by Western blot; miR-503 mimics were transiently transfected to the BEL-7402 cells by liposome transfection; potential target genes of miR-503 were predicted by Bioinformatics software; miR-503 potential targets were validated by dual luciferase activity; and the cell viability was measured by MTT assay. 
 Results: MiR-503 level was down-regulated and Bcl-2 protein expression level was up-regulated in BEL-7402 cells compared with HL-7702 cells. MiR-503 could interact with bcl-2 and inhibit its expression. Cell vitality with miR-503 transfection was significantly reduced compared to that in the negative control.
 Conclusion: MiR-503 may enhance the sensitivity of BEL-7402 cells to cisplatin and inhibit the cell proliferation by targeting bcl-2.

With the breakthroughs achieved of programmed death-1 (PD-1)/PD-L1 inhibitors monotherapy as first-line and second-line treatment in advanced non-small cell lung cancer (NSCLC), the treatment strategy is gradually evolving and optimizing. Immune combination therapy expands the benefit population and improves the curative effect. A series of randomized phase III trials are ongoing. In this review, we discuss the prospect and current situation of immune checkpoint inhibitors in first-line treatment in advanced NSCLC patients.

Precision medicine demands accurate assessment of tumor response to therapies with the purpose of timely optimization or adjustment of the given treatment regimens. Chemoradiation remains the standard of care in advanced lung cancers and imaging-based noninvasive response evaluation could improve therapeutic efficacy and reduce treatment-related severe side effects. In this review, we overviewed the applications and pitfalls of major imaging modalities in response evaluation in lung cancer from a quantitative perspective. The development of radiomics will provide more precise information for treatment predicting, evaluation and prognosis.

To explore the mechanism of apoptosis for resvertrol-mediated reversing the drug-resistance of AML HL-60/ADR cells.

To Study the effect of C677T and MTHFR gene polymorphism on side effects of HD-MTX in ALL children.

Objective To investigate the mechanism by which epirubicin (EPI) induces autophagy and the mechanism by which tea polyphenol (TP) regulates EPI-induced autophagy and apoptosis in T24 bladder cancer cells. Methods T24 cells weredivided into control group, EPI group, TP group and TP plus EPI group. Eight hours after corresponding treatments in different groups, transmission electron microscopy (TEM) was used to observe the image of autophagosomes. The expressions of autophagy-related protein LC3II and p62 in the cells were detected by Western blotting. Apoptotic cells were evaluated after EPI-treatment for 24 hours by flow cytometry combined with annexin V-FITC/PI staining. Western blotting was performed to determine the levels of cleaved-caspase-3 (c-caspase-3) and cleaved-PARP (c-PARP). LC3II was again tested by Western blotting 8 hours after T24 cells were treated with EPI added with autophagy pathway inhibitor chloroquine and 3-methyladenine, and moreover, the levels of LC3II and p-JNK were detected by Western blotting after T24 cells were treated with EPI combined with TP or the JNK inhibitor SP for 8 hours. Results The amount of autophagosomes and the level of LC3IIin TP plus EPI group were much lower than those in EPI group. SP reduced the level of LC3II induced by EPI. EPI increased p-JNK in a time-dependent manner. TP combined with EPI reduced the activity of JNK pathway. The apoptosis rate and the levels of c-caspase-3 and c-PARP in TP plus EPI group were much higher than those in EPI group. Conclusion TP inhibits autophagy through JNK pathway to enhance EPI-induced apoptosis in T24 bladder cancer cell line.