To observe the effectiveness of grain-moxibustion in resisting oxidative stress in doxorubicin (DOX)-induced cardiomyopathy rats.

A target cell extraction-chemical profiling method based on human alveolar adenocarcinoma cell line (A549 cells) and UHPLC/LTQ Orbitrap MS for screening the anti-lung cancer bioactive compounds from Curcuma longa has been developed in this paper. According to the hypothesis that when cells are incubated together with the extract of Curcuma longa, the potential bioactive compounds in the extract should selectively combine with the cells, then the cell-binding compounds could be separated and analyzed by LC-MS. The bioactive compounds in C. longa are lipophilic components. They intend to be absorbed on the inner wall of cell culture flask when they were incubated with A549 cells, which will produce interference in the blank solution. In this paper, by using cells digestion and multi-step centrifugation and transfer strategy, the interference problem has been solved. Finally, using the developed method, three cell-binding compounds were screened out and were identified as bisdemethoxycurcumin, demethoxycurcumin, and curcumin. These compounds are the main bioactive compounds with anti-lung cancer bioactivity in C. longa. The improved method developed in this paper could avoid the false positive results due to the absorption of lipophilic compounds on the inner wall of cell culture flask, which will to be an effective complementary method for current target cell extraction-chemical profiling technology.

To determine the characteristics and clinical significance of outer retinal tabulation (ORT) in wet age-related macular degeneration (wAMD) treated by anti-vascular endothelial growth factor (anti-VEGF) through optical coherence tomography (OCT).

To investigate the influence of interferon-alpha-2b (IFN-α2b) with JAK2 kinase, COX-2 and microvessel density in patients of MPN and the relation of JAK2V617F and COX-2 in human erythroleukemia cell line (HEL) cells.

To investigate the relationship between sensitivity to cisplatin (DDP) and the expression of HSP70 in cervical cancer cells in vitro.

Glucocorticoid receptor (GR) is identified as a member of nuclear receptor family. To exert its biological action, the ligand bound GR is translocated from the cytoplasm into the nucleus by regulating transcriptional signals of related genes. In clinical practice, the effects of glucocorticoid are often mediated by GR signaling pathways. An increasing number of studies have indicated that GR signaling pathways play an essential role in the proliferation, invasion and prognosis of bladder cancer. Meanwhile, the new-generation selective GR activator improves its anti-tumor effects, and at the same time reduces the adverse reactions of hormones, which probably raises the prospect for the treatment of bladder cancer.

Artemisinin is an anti-malarial drug with poor water solubility and oral absorption; so a variety of derivatives based on the parent nucleus have been developed. Compared with artemisinin, dihydroartemisinin (DHA) has a stronger anti-malaria activity, and has the advantages of high metabolic rate and better water solubility. Recent studies have discovered that DHA has a good inhibitory effect on tumor cells, which is closely related to the peroxide bridge in its molecular structure. Since tumor cells need more Fe3+ than normal cells, there are a large number of transferrin receptors on the tumor cell membrane. DHA can break the peroxide bridge in the presence of Fe2+, and the free radicals generated can play its lethal effect on tumor cells. In addition, DHA can promote endocytosis of transferrin receptor, and thus prevent cancer cells from taking Fe3+ from microenvironment. This article reviews the anti-tumor molecular mechanism of DHA, including accelerating oxidative damage, inducing apoptosis, inhibiting the growth, proliferation and invasion of tumor cells, reversing tumor multidrug resistance.

To investigate the reversal effect of methylseleninic acid on cisplatin (DDP)-resistant ovarian cancer cells and the underlying mechanisms.
 Methods: SKOV3/DDP cells were incubated with cisplatin at different concentrations for 48 h, then the proliferation rate of SKOV3/DDP cells was detected by MTT assays, and the expression of β-catenin in SKOV3/DDP cells was examined by Western blot. The inhibitory effect of methyl-seleninic acid (MSA) combined with DDP at different concentrations on SKOV3/DDP cells was assayed by MTT method. Western blot was used to detect the expression of β-catenin protein in the cells.
 Results: The inhibitory rate for proliferation in DDP-treated SKOV3/DDP cells with different concentrations is lower than that in the SKOV3 cells (P<0.05); β-catenin expression in SKOV3/DDP cells was significantly higher than that in the SKOV3 cells (P<0.05). The inhibitory rate for proliferation in SKOV3/DDP cells with different concentrations of MSA was increased with the increase in concentration (P<0.05). The inhibitory rate for proliferation in SKOV3/DDP cells with 2 or 6 μmol/L MSA plus cisplatin was lower than that in cisplatin alone group (P<0.05). β-catenin expression in SKOV3 /DDP cells with 2 or 6 μmol/L MSA plus cisplatin was higher than that in the cisplatin alone group (P<0.05).
 Conclusion: MSA can reverse cisplatin resistance on SKOV3 / DDP cells, which may be related to the decrease in β-catenin expression.

Objective: To investigate the effects of berberine in combination with bortezomib on proliferation and apoptosis of multiple myeloma (MM) cell line. Methods: MM cell line U266 cells were treated with berberine and/or bortezomib. The effects of berberine and/or bortezomib on proliferation of cells were measured by methylthiazolyl tetrazolium bromide (MTT). Flow cytometric Annexin Ⅴ/PI double staining method was used to detect effect of either drug alone or in combination on apoptosis of MM cell line U266. ELISA was used to measure the expression of casepase-3,-8,-9 affected by the two drugs. Western blot was used to detect the expression of the apoptosis-related protein TRADD and FADD. King formula was used to determine if there was a synergistic effect of berberine in combination with bortezomib. Results: ① Both berberine and bortezomib as single agent had dose- and time-dependent effects of proliferation inhibition on U266 cells. Berberine (20 μmol/L) and bortezomib (5 nmol/L) had a synergistic effect of proliferation inhibition (Q value: 1.31-1.65). ② The proportion of early stage apoptosis in both single agent groups and combination group significantly increased compared to control group (P< 0.05). Berberine and bortezomib had a synergistic effect on cell apoptosis (Q value after 6 h and 12 h were 0.896 and 1.197, respectively). ③ Berberine in combination with bortezomib significantly upregulated expressions of caspase-3, -8 and -9, which were statistically significant (P<0.05). ④Berberine in combination with bortezomib significantly upregulated expressions of TRADD (0.91±0.01, 0.70±0.01) and FADD (0.98±0.01, 0.98±0.01) compared with control group (both P<0.05). Conclusion: Berberine in combination with bortezomib had synergistic effects on proliferation inhibition and apoptosis, which were mediated by up-regulated levels of TRADD and FADD.

The combination therapy of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has attracted the attention of more and more investigators. The aim of this meta-analysis is to evaluate the clinical efficacy and safety of intercalated combination of chemotherapy and EGFR- TKIs versus chemotherapy alone in the first-line therapy of advanced non-small cell lung cancer (NSCLC).

Amorphigenin, a rotenoid compouns, from seeds of Amorpha fruticosa, has been shown to possess anti-proliferation activities in several cancer cells. To explore the antitumor effects of amorphigenin on cisplatin-resistant human lung adenocarcinoma A549/DDP cells and explore the underlying mechanisms.

To investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.

Anaprazole is a proton pump inhibitor clinically used for curing peptic ulcer. A rapid, sensitive and convenient LC-MS/MS method was first established for the determination of anaprazole in human plasma. d(3), (13)C-anaprazole was used as internal standard (IS). After extraction from human plasma by protein precipitation with acetonitrile, all components were separated on an Extend C(18) column (100 mm × 4.6 mm, 3.5 μm). The assay was linear over the concentration range of 5.00-3 000 ng·m L(-1) (r(2) > 0.995). The method was successfully applied to a pharmacokinetic study of 40 mg anaprazole enteric-coated tablets in 14 Chinese healthy volunteers under fasting or high fat diet conditions. C(max) was (1 020 ± 435) ng·m L(-1) and AUC(0-t) was (2 370 ±754) h·ng·m L(-1) under fasting condition. And C(max) was (538 ± 395) ng·m L(-1) and AUC(0-t) was (1 610 ± 650) h·ng·m L(-1) under high fat diet condition. The plasma results suggest that the exposure of anaprazole is reduced by the high fat diet.

Eighteen novel ciprofloxacin-histone deacetylase inhibitor (HDACi) conjugates were designed and synthesized from suberic acid and ciprofloxacin via esterification and amidation reaction. All conjugates were confirmed by the application of (1)H NMR and HR-MS spectra, their activities against HDACs were evaluated by HDACs assay kit and the anti-tumor activities were evaluated in five cancer cells with CCK-8 assay. The preliminary biological results showed that these conjugates displayed potent activity against HDACs and significant anti-proliferative effect on the cancer cells. Some conjugates exhibited activities better than that of the parent compound ciprofloxacin and drug SAHA. Specifically, compound 12b exhibited the most potent anti-HDAC1 (IC(50) = 0.041 ± 0.005 μmol·L(-1)) and HDAC6 (IC(50) = 0.039 ± 0.006 μmol·L(-1)) activities, and also showed the greatest potency against NCI-H460 (IC(50) = 0.7 ± 0.04 μmol·L(-1)) and A549 (IC(50) = 0.9 ± 0.12 μmol·L(-1)). These results suggest that the histone deacetylase inhibitors have significant anti-tumor activities, which can enhance the anti-tumor activity of quinolones

To investigate the role of pannexin 1 channels in cisplatin-induced apoptosis in I-10 cells and the mechanisms.

Objective: To investigate the effect of silencing DJ-1 on xenografted human laryngeal squamous cell carcinoma (LSCC) Hep-2 cells in nude mice. Methods: Xenograft model of human LSCC was established by subcutaneous transplantation of Hep-2 cells in 24 nude mice. The LSCC-bearing nude mice were randomly divided into 3 groups (n=8 in each):DJ-1 siRNA low dose group and DJ-1 siRNA high dose group were injected in tumors with 20 μg of DJ-1 siRNA or 40 μg of DJ-1 siRNA in 50 μL, respectively; control group was injected with 5% glucose solution in 50 μL, twice a week for 3 weeks. The weight and size of tumors were measured before injection. The animals were sacrificed 48 h after the final treatment, and the tumors were harvested and weighed. The apoptosis and proliferation of tumor cells were determined; the expressions of Caspase-3 and Ki-67 in tumor specimens were detected with immunohistochemistry. The expression of DJ-1, PTEN, survivin mRNA and protein in tumor tissues were detected by RT-PCR and Western blotting, respectively. Results: Tumor weight in low dose group[(0.66±0.15)g] and high dose group[(0.48±0.11)g] were significantly lower than that in control group[(0.83±0.16)g, all P<0.05]. The inhibition rates of low dose group and high dose group were (20.48±0.18)% and (42.16±0.13)%, respectively. Immunohistochemistry showed that the expression of Caspase-3 was increased and Ki-67 was reduced in tumor specimens, compared with the control group (all P<0.05). RT-PCR and Western blot results showed that in low dose group and high dose group the mRNA and protein expression of DJ-1 and survivin significantly decreased (all P<0.05), while PTEN mRNA and protein content increased (all P<0.05). Conclusion: High dose DJ-1 siRNA can inhibit the tumor growth in human LSCC xenograft nude mouse model, which indicates that down-regulating DJ-1 and survivin, and up-regulating PTEN expression may lead to blockage of PI3K-PKB/Akt signaling pathway and promoting tumor cell apoptosis.

To discover novel dihydropyridin-2-one derivatives with higher HDAC inhibitory activity and subtype selectivity, twenty-seven dihydropyridin-2-one derivatives containing triazole unit were synthesized via click chemistry. The structures of these compounds have been confirmed by IR, 1H NMR and HR-MS spectra. Preliminary in vitro pharmacological tests showed that these compounds potently inhibited HDAC1 and HDAC6, which also displayed significant antiproliferative effect on five cancer cells, and most of them were better than that of the parent compound 1A and drug SAHA. Specifically, compound 18g exhibited most potent anti-HDAC1 activity, and also showed the greatest potency against PC-3 and Hep G2. Additionally, all compounds were nontoxic to health RWPE-1 and VERO cells, while SAHA showed essential toxicity.

Fibroblast growth factor receptors (FGFRs) are in the superfamily of receptor tyrosine kinases’ (RTKs). Fibroblast growth factors (FGFs) bind to FGFRs with high-affinity, involving in many biological processes, such as the regulation of organ development, angiogenesis, cell proliferation, migration and anti-apoptosis. The activating mutations and amplification of the FGFR gene, resulting in FGFR protein amplification, are closely associated with the development and progression of many malignancies in human. In recent years, various small molecule FGFR inhibitors with different chemical backbones are designed, synthesized, and mainly applied to the clinical anti-cancer research. This article is devoted to review of selective second generation of small molecule FGFR inhibitors that are currently used in clinical trials, and the interaction with the FGFR protein, in order to provide strategies to the design of small molecule FGFR inhibitors.

Inosine 5’-monophosphate dehydrogenase(IMPDH) is a rate-limiting enzyme in de novo biosynthesis of guanine and plays an important role in cell proliferation. In clinic, IMPDH inhibitors are mainly used in fields of anticancer, antiviral, anti-parasitic, and immunosuppressive chemotherapy. However, since there are usually great inter- and intra-individual variability between drug concentration and clinical effect of IMPDH inhibitors, the enzyme activity of IMPDH may be applied as a specific biomarker and combined with the pharmacokinetics (PK) monitoring to improve efficacy and safety of IMPDH inhibitors. This review aims to discuss the assay of IMPDH activity measurement and its clinical application in recent years and provide valuable insights and theoretical basis for the development of IMPDH inhibitors’ pharmacodynamics monitoring.

To study the role and molecular mechanism of epigallocatechin gallate (EGCG) in reversing drug-resistance to 5-fluorouracil (5-FU) in gastric cancer drug-resistant cell line SGC-7901/5-FU.