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.

The management of retinoblastoma (RB) has dramatically changed over the past two decades. The introduction of chemotherapy has transformed treatment algorithms completely. Chemotherapy is currently used as a first line approach for children with RB and can be delivered by intravenous, intra-arterial and intravitreal routes. However, there still remains some controversy on the treatment of advanced RB, especially in eyeball salvage. This article described domestic and international approaches to eyeball salvage treatment. We would like to further discuss our opinion on the management of advanced RB based on our clinical experience for attracting more clinical concern on this issue. Many factors should be considered when choosing the appropriate conservative therapy. The choice of eyeball salvage treatment not only depends upon the tumor staging and laterality but also upon compliance and economic factors. Doctors and parents should not blindly pursue eye saving. However, there are still cases where enucleation is definitely the treatment of choice. (Chin J Ophthalmol, 2016, 52: 728-732).

Chemotherapy is a common adjuvant therapy for breast cancer that improves survival rates by killing residual cancer cells. However, this intervention may damage the germ cells within the ovary and interrupt the menstrual cycle, ultimately leading to chemotherapy-induced amenorrhea (CIA). The incidence of CIA depends on how broadly this term is defined. Around 75% of premenopausal breast cancer women treated with chemotherapy will develop CIA. Age, having a relatively long chemotherapy cycle duration, being estrogen-receptor positive, and using Tamoxifen all increase the risk of CIA. Although CIA may be associated with better prognosis outcomes, breast cancer women must subsequently deal with the various menopausal symptoms that are associated with a CIA-induced drop in estrogen level (such as cognitive function decline, physical and psychological symptoms, vasomotor symptoms, reproductive and sexual function problems, and body weight change). The present article describes the female menstrual cycle, the mechanism and risk factors of CIA, and the range of menopausal symptoms. Furthermore, we summarized methods of assessing menopausal symptoms and compared five common rating scales of menopausal symptoms. By better understanding the potential menopausal symptoms, researchers and clinicians may then select the most appropriate scale based on the situational needs in order to evaluate the severity of menopausal symptoms that are experienced by breast cancer women.

As extremely important inflammatory cells in the tumor microenvironment, tumor-associated macrophages (TAMs) can secrete a variety of chemokines and cytokines, which play an important role in the occurrence of tumor growth and metastasis. Recent years, increasing studies have shown that macrophages are associated with tumor chemotherapy sensitivity. The chemical substances produced by macrophages affect the efficacy of chemotherapeutic agents. In addition, some chemotherapeutic agents have an effect on the recruitment and bioactivity of macrophages in the tumor issue, which influences the anti-tumor efficacy of chemotherapy drugs. In this review, we summarize the roles of macrophages in the chemotherapy resistance, including the regulatory mechanism and the strategy of targeting macrophages.

Objective To observe the expressions of c-Src protein and nucleophosmin/B23 (NPM1) protein in lung adenocarcinoma tissues and explore their relationships with chemotherapeutic efficacy. Methods The study collected a total of 107 lung adenocarcinoma tissue specimens from the First People's Hospital of Huaihua City from 2012-10-10 to 2015-06-30. Immunohistochemistry was used to analyze the expressions of c-Src protein and NPM1 protein. The relationships between the protein expressions and lung adenocarcinoma progression were subsequently analyzed. Among these patients, 55 cases of III-IV patients were treated with gemcitabine combined with cisplatin for 4 cycles of chemotherapy. The relationships between the protein expressions and chemotherapeutic efficacy were then analyzed. Results Both c-Src protein and NPM1 protein were positively expressed in lung adenocarcinoma tissues. With the increase of clinical stages, their expression levels gradually increased. However, their levels showed an inverse correlation with tumor differentiation degree. Chemotherapeutic efficacy decreased with the increase of the protein expressions. Conclusion Chemotherapeutic sensitivity is poor in lung adenocarcinoma patients overexpressing c-Src and NPM1 protein. High expressions of c-Src and NPM1 may be associated with poorly differentiated adenocarcinoma.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a group of targeted-drugs which effectively inhibits the growth of tumor cells with sensitive mutations in EGFR. However, the innate and acquired resistance are major obstacles of the efficiency. Autophagy is a highly conserved self-digesting process in cells, which is considered to be associated with cancer development andchemoresistance. The activation of EGFR may regulate autophagy through multiple signal pathways. EGFR-TKIs can induce autophagy, however, the function of the inducted autophagy remains biphasic. On one hand, autophagy induced by EGFR-TKI acts as a cytoprotective response in cancer cells, and autophagy inhibitors can enhance the cytotoxic effects of EGFR-TKI. On the other hand, a high level of autophagy after treatment of EGFR-TKI can also result in autophagic cell death lacking features of apoptosis, and the combination of EGFR-TKI with autophagy inducer might be beneficial. Thus, autophagy regulation represents a promising approach for improving the efficiency of EGFR-TKI in the treatment of cancer patients. Here we summarized the signaling pathways involved in EGFR-TKI induced autophagy, and reviewed the roles of autophagy in the treatment and chemoresistance of EGFR-TKI treatment in lung cancer.

Small cell lung cancer (SCLC) is a rapidly growing tumor with characteristic of neuroendocrine cellular function. Neuron specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP) and lactic dehydrogenase (LDH) are valuable in diagnosis and treatment of SCLC. By analyzing the variation of NSE, ProGRP and LDH before and after treatment, the aim of this study is to investigate the efficacy of tumor markers in diagnostic staging, therapeutic evaluation and prediction of disease relapsing.

A great individual differences to chemotherapeutic effects existed in the patient with advanced lung cancer. How to choose the optimum regimens to achieve the individuation and maximum effect of chemotherapy for lung cancer is worth exploring. The study was designed to examine the effect of ex vitro chemo-sensitivity assay in xeno-free culture of autologous malignant effusion cells from patients with advanced lung adenocarcinoma.

To investigate the inhibition effect of β-elemene on the growth and metastasis of laryngeal carcinoma and the underlying mechanism.

Objective To establish a gastric cancer cell line with stable Drosha silenced and explore the effect of Drosha on the chemosensitivity of gastric cancer cells to epirubicin. Methods Interfering sequences targeting Drosha were designed and inserted into the lentiviral vectors, which were used to transfect MGC-803 cells. The level of Drosha mRNA was detected by quantitative real-time PCR; Drosha protein was detected by Western blotting; MTT assay was performed to test the 50% inhibitory concentration (IC50) of epirubicin agaisnt wide-type MGC-803 cells. After the treatment with IC50 epirubicin, the apoptosis rate of each cell group was determined by flow cytometry; the expressions of apoptosis-related proteins caspase-3, caspase-9, Bax, Bcl-2 were assessed by Western blotting. Results The gastric cancer MGC-803 cells with stable Drosha silenced were successfully established, and the levels of Drosha mRNA and protein were reduced. After the cells were treated with 0.5 mg/L(IC50) epirubicin, the apoptosis rate of MGC-803 cells was raised, the protein expressions of caspase-3 , caspase-9 and Bax were significantly upregulated and Bcl-2 was downregulated. Conclusion The silence of Drosha expression can promote the sensitivity of gastric cancer to epirubicin.

Apoptosis, a form of programmed cell death, is a critical defense mechanism against the formation and progression of cancer. In vivo, apoptosis functions to eliminate potentially deleterious cells without causing such adverse effects as inflammatory response, and to ensue scar formation. Therefore, activation of the apoptotic pathways becomes an intriguing strategy in the development of chemotherapeutic agents. Marine natural products have become an important source in the discovery of antitumor drugs now since it is more and more feasible to collect organisms from seas. Hundreds of marine compounds have been found to induce apoptosis in tumor cells in recent years and many of them have good antitumor activity. This review summarizes several such compounds, based on their effects on the apoptotic signaling pathways, and highlights the problems in the development of anti-cancer drugs from the natural products.

Tamoxifen (TAM) is the most common nonsteroidal antiestrogen agent, which has been widely used in the prevention of recurrence of estrogen or progesterone receptor-positive breast cancer in patients. It is metabolized by cytochrome P450 oxidases to its active metabolite (4-hydroxytamoxifen, 4-OH-TAM) and endoxifen (EDF), which played a critical role in the therapy. 4-OH-TAM and EDF have 30- to 100-fold more potency than TAM in the suppression of estrogen-dependent breast cancer cell proliferation. CYP3A4 and CYP2D6, as the key drug-metabolizing enzymes in those metabolic actions, are known to have several alleles. Genetic polymorphisms of CYP2D6 and CYP3A4 will influence the plasma concentrations of active TAM metabolites and clinical outcomes for breast cancer patients treated with TAM. The genetic polymorphisms of drug transporters, involved in the disposition of active TAM metabolites, also have the potential to influence the plasma concentrations of active TAM metabolites and clinical outcome for the treatment of breast cancer. In this review, we summarized the association of the genetic polymorphisms in the metabolic enzymes and transporters involved in the metabolism and disposition of TAM with the metabolite concentration, efficacy and adverse effects of TAM, which provides a fundamental reference for further pharmacogenomic study and clinical use of TAM.

Salinomycin is a monocarboxylic acid polyether antibiotics produced by Streptomyces albus. It has strong inhibiting and killing activity against most gram-positive bacteria and various coccidiums with low adverse impact on environment. In addition, salinomycin can specifically inhibit the growth of a variety of cancer cells and cancer stem cells via targeting to multiple sites, and is a promising anti-tumor drug candidate. To obtain high yield salinomycinproducing strain, conventional mutation techniques and modern molecular genetic methods have been used. Meanwhile, bioactivity and selectivity of salinomycin could be improved by modifying the chemical structure and changing drug delivery methods. Here, we summarize the key strategies for enhancing salinomycin production and review the progresses in optimizing its drug activity and targeting properties. The future research focus is also addressed.