To explore the effect of homoharringtonine(HHT) combined with imatinib(IM) on proliferation and apoptosis of K562/G01 cells and its potential mechanism.

To investigate the effects of Btk inhibitor (PCI-32765) and BCR-ABL tyrosine kinase inhibitor (Dasatinib) on proliferation and apoptosis of acute lymphoblastic leukemia (ALL) cell lines (Sup-B15, RS4;11) and the possible mechanism.

Pembrolizumab, an inhibitor target programmed death 1 (PD-1), was approved into the first line therapy in advanced non-small cell lung cancer (NSCLC). It was a milestone that immune checkpoints drugs have played an important role in the treatment system of NSCLC. The results of clinical trials revealed the superiority of PD-1/programmed death ligand 1 (PD-L1) inhibitors compared with chemotherapy in first-line, second-line and multidrug resistance phase therapy. Objective response rate (ORR) was up to 80% with pembrolizumab plus chemotherapy, and progression-free survival (PFS) with single pembrolizumab in first line was nearly 1 year (10.3 months), the hazard ratio for death fell by 40%. Overall survival (OS) was more or less 1 year with single drug pembrolizumab, nivolumab and atezolizumab for second line therapy. PD-L1 expression was a predictor of PD-1/PD-L1 inhibitors. The positive rate of PD-L1 (more than 1%) in advanced NSCLC was about 60% with little difference between the tissue types. However, there was no gold standard test of PD-L1 expression.

A survival analysis and the influencing factors for non-small cell lung cancer (NSCLC) patients with brain metastases accepting first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) treatment have not yet been elucidated to date. In this study, we collected and analyzed the survival data of NSCLC patients with brain metastasis to obtain evidence and to provide guidance in clinical practice.

Objective: In this study, a primary culture system for the rat distal pulmonary arterial smooth muscle cell (PASMC) was established to observe the effect of Bortezomib a treatment on the basal intracellular calcium concentration ([Ca(2+) ](i)), store operated calcium entry (SOCE) and Orai-1 expression in rat PASMC. Methods: We employed the primary culture method for the rat distal PASMC including the enzymatically dissociation of PASMC from the freshly isolated distal pulmonary artery and the culture of PASMC. The In Cyte system was used to measure the basal [Ca(2+) ](i) and SOCE after substantial treatment.Orai-1 protein expression in rat pulmonary artery smooth muscle was detected by Western blot. Results: Compared with Hypoxia group, the basal [Ca(2+) ](i) were significantly reduced in Hypoxia+ BTZ group(P<0.01). The basal [Ca(2+) ](i) A340/A380 ratio of Normoxia group was(1.07±0.02). The basal [Ca(2+) ](i) of Hypoxia group was(1.49±0.03); The Hypoxia+ BTZ group was(1.17±0.03). Compared with Hypoxia group, the store operated calcium entry were significantly reduced in Hypoxia+ BTZ group(P<0.01). The SOCE A340/A380 ratio of Normoxia group was(0.56±0.02). The SOCE of Hypoxia group was(0.84±0.02); The Hypoxia+ BTZ group was(0.66±0.02). The level of Orail-1 protein in pulmonary artery smooth muscle of Hypoxia group was (181.5±12.7)% higher than control group which was(100±0)%, (P<0.05). In the Hypoxia+ BTZ group Orai-1 protein expression was recovered(146.7±15.1)%, (P<0.05). Conclusion: Bortezomib inhibit chronically hypoxic enhancement of Orail-1 protein expression, basal [Ca(2+) ](i) and SOCE in rat distal pulmonary arterial smooth muscle cells.

Objective: To investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinomas before and after acquiring resistance to EGFR tyrosine kinase inhibitors (TKIs) using ARMS method followed by further verification using droplet digital PCR technique. Methods: Twenty qualified patients were included, among them 13 were male and 7 were female patients. Before EGFR-TKIs treatment, 5 patients were EGFR wild-type by ARMS, and the other 15 patients had L858R or 19-del point mutations. The time to progression varied from 4 to 18 months. Mutation of exons 18, 19, 20 and 21 were detected by ARMS, and were verified by droplet digital PCR system method. Results: EGFR wild-type status was unchanged before and after acquired resistance to EGFR-TKIs in 5 lung adenocarcinoma patients. Alteration of EGFR mutation status occurred in 10 of the 15 patients with pre-treatment L858R or 19-del mutations. Among them, T790M mutation was found in 8 patients, L858R became G719X plus S768I mutation in one patient, and 19-del converted into wild-type in one other patient. Conclusions: T790M mutation is the primary type of EGFR mutation in lung adenocarcinomas with acquired resistance to EGFR-TKIs therapy. Acquired resistance to EGFR-TKIs dose not lead to the alteration of EGFR status in pre-treatment EGFR wild-type patients, but can alter EGFR mutation status in pre-treatment EGFR mutant patients.

Objective To observe the regulation of Shuanghuang Shengbai Granule (SHSBG) on regulating Wnt signaling pathway in tumor-bearing mice with chemotherapy induced myelosuppression. Methods Chemotherapy induced myelosuppression model was established in Lewis lung tumor bearing mice by intraperitoneal injection of cyclophosphamide (CTX). And then they were intervened by SHSBG. Routine white blood cell (WBC) count, red blood cell (RBC) count, platelet count, and tumor mass were calculated. Ratios of bone marrow hematopoietic stem cell (Sca, CD34 double positive cells) were detec- ted by flow cytometry. mRNA expression of main genes in Wnt signaling pathway (Wnt, β-catenin, Frizzted, DSH, GSK3) were detected using real time fluorescent quantitative PCR. Results The number of WBC and ratio of hematopoietic stem cells in the treatment group were higher than those in the model group (P<0. 05). Expressions of Wnt, β-catenin, Frizzted, DSH, and GSK3 mRNA in the bone marrow were higher in the treatment group than in the model group (P <0. 05). Expressions of Wnt, β-catenin, Frizzted, and DSH mRNA expression in tumors were lower in the treatment group than in the model group (P <0. 05). There was no statistical difference in counts of RBC and platelet, tumor mass, or GSK3 mR- NA expression among all groups (P >0. 05). Conclusions The mechanism for SHSBG treating myelo-suppression was related to regulating Wnt signaling pathway. Besides, it had dual regulation effect on Wnt signaling pathway, up-regulating expressions of main genes in Wnt signaling pathway while inhibiting ex- pressions of partial genes in tumors.

To investigate the effect of sodium phenylbutyrate (SPB) in modulating docetaxel resistance in human prostate cancer cells in vitro.

To investigate the effects of polyunsaturated fatty acids (PUFA) ω-3 and ω-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism.

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.

Objective: To prepare the Fe3O4-loaded biodegradable liquid-solid phase inversion poly(lactic-co-glycolic acid) (PLGA) in situ implant for ultrasound-guided injection into nude mouse tumor model, and to investigate its clinical effect in thermomagnetic treatment of nude mice with human liver cancer SMMC-7721 cells in an alternating magnetic field. Methods: An in situ implant containing 10% Fe3O4 was prepared, and 50 μl Fe3O4-PLGA-NMP gel was injected into the subcutaneous tissue of Kunming mice. The degradation of this material was observed for 2 consecutive months, and the changes in body weight were recorded. HE staining and Prussian blue staining were performed for the heart, liver, spleen, lung, and kidney of Kunming mice. Fresh ex vivo bovine liver was taken and cut into cubes with a dimension of 2 cm×2 cm×2 cm and then 50 μl Fe3O4-PLGA-NMP gel was injected; after phase inversion, the cubes of ex vivo bovine liver were heated for 1, 2, 3, 4, and 5 minutes, respectively, and then cut open for observing the range of ablation; HE staining was also performed. Micro-CT scan was performed after ultrasound-guided injection of 50 μl Fe3O4-PLGA gel into the tumors of the nude mice, and then the nude mice were divided into treatment group and control group. The mice in the treatment group were given thermomagnetic treatment for 3 minutes, and tumor growth was observed daily. Results: The biodegradation of Fe3O4-PLGA-NMP implant showed that the subcutaneously injected material was gradually metabolized at 2 weeks after injection and that the nude mice were in good condition. The bovine liver ablation experiment showed that the range of ablation of 50 μl Fe3O4-PLGA implant reached 1.46 ± 0.11 cm. HE staining showed that part of bovine liver had coagulative necrosis. The phase inversion experiment of Fe3O4-PLGA gel showed quick liquid-solid phase inversion of the material after injection into the tumor, and the process of liquid-solid phase inversion could be monitored by ultrasound and CT. The detachment and incrustation of the tumor started at 2 days after treatment, the wound started to heal 15 days later, and the tumor tissue disappeared completely. Conclusion: Ultrasound-guided injection of biodegradable Fe3O4-PLGA in situ implant combined with magnetic thermal ablation can effectively treat human liver cancer SMMC-7721 cells in nude mice.

Objective: To investigate the effect of triptolide on human oral cancer cell (HB) proliferation and phosphates and tensin homologue deleted on chromosome ten gene (PTEN) mRNA expression in oral cancer. Methods: The cancer cells were cultured in the medium containing triptolide of different concentrations for 24, 48 and 72 h. Methyl thiazolyl tetrazolium (MTT) method was used to test the rate of growth inhibition of cancer cells, flow cytometer to detect the change of cell cycle and reveres transcription-PCR (RT-PCR) to examine the expression of PTEN mRNA. The expression of PTEN protein was examined by Western blotting. Results: The rate of growth inhibition was (26.92 ± 0.14)%, (38.67 ± 0.11)%, (72.62 ± 0.89)% and (90.42 ± 0.28)%, respectively. The corresponding expression of PTEN mRNA was (3.59±0.21)%, (5.27±0.40)%, (7.18±0.44)% and (9.16±0.50)%, respectively and the corresponding A value of PTEN protein was 0.135±0.007, 0.410±0.020, 0.447±0.017 and 0.884±0.066, respectively. The proportion of G1 phase cells increased from (58.78±0.98)% to (84.13±0.47)%, but the proportion of S phase cells decreased from (25.40±0.43)% to (9.41±0.73)%. Conclusions: The triptolide not only had inhibitory effect on the HB proliferation, but also affected the cell cycle.

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 evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95%CI 13.5-16.3) and the OS was 37.0 weeks (95%CI 27.9-46.1). Patients with brain metastases showed higher ORR(P=0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ(P=0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

This study was designed to elucidate the chemical composition and anti-cancer effects of Schizonepeta tenuifolia’s ethanol extracts. Microfluidic technology was used in the study of Schizonepeta tenuifolia from 9 different geographic regions. The ethanol extracts were examined with HPLC to establish their Fingerprints in order to analyze the relationship between the spectrum and efficacy index through Grey Correlation software, and a rapid HPLC-Q-TOF/MS method was established. The result shows that chromatographic peaks of the 19, 6, 11, 16, 18th are the representative diosmetin, luteoloside, hesperidin, luteolin, and apigenin. The 10, 12, 20th peaks may be naringenin-7-O-glucuronide or quercitrin, rosmarinate or acetylcorynoline, and 5,7-dihydroxy-6,4-dimethoxy flavone. The major chemical composition of Schizonepeta tenuifolia was found to have the anti-lung-tumor effects. A new method was established for the quality control of traditional Chinese medicine.

To investigate the anti-prostate cancer (PCa) effect of roemerine in vitro and in vivo in the mouse model of PCa.

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.