Xin-Xin Wang

The effects of artesunate on the expression of EGFR and ABCG2 in A549 human lung cancer cells and a xenograft model.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Clinical and laboratory studies have suggested that multi-targeting approaches against neoplastic cells could help to increase patient survival and might reduce the emergence of cells that are resistant to single-target inhibitors. Artesunate (ART) is one of the most potent and rapidly acting antimalarial agents known, and it also exerts a profound cytotoxic activity toward cancer cells and reverses multi-drug resistance. In the present study, we found that artesunate inhibited NSCLC A549 cell growth and proliferation, induced apoptosis and suppressed tumor growth in a dose-dependent manner in A549 cells and a mouse xenograft model. Furthermore, artesunate down-regulated the expression of epidermal growth factor receptor (EGFR), Akt and ATP-binding cassette subfamily G member 2 (ABCG2) at the mRNA and protein levels in vitro and in vivo. In conclusion, artesunate is an effective anti-cancer drug that may enhance the effectiveness of other anticancer drugs and may reverse multi-drug resistance by suppressing the transcription of ABCG2, which inhibits drug efflux.

Microarray-based analysis of microRNA expression in breast cancer stem cells

BackgroundThis study aimed to determine the miRNA profile in breast cancer stem cells (BCSCs) and to explore the functions of characteristic BCSC miRNAs.MethodsWe isolated ESA+CD44+CD24-/low BCSCs from MCF-7 cells using fluorescence-activated cell sorting (FACS). A human breast cancer xenograft assay was performed to validate the stem cell properties of the isolated cells, and microarray analysis was performed to screen for BCSC-related miRNAs. These BCSC-related miRNAs were selected for bioinformatic analysis and target prediction using online software programs.ResultsThe ESA+CD44+CD24-/low cells had up to 100- to 1000-fold greater tumor-initiating capability than the MCF-7 cells. Tumors initiated from the ESA+CD44+CD24-/low cells were included of luminal epithelial and myoepithelial cells, indicating stem cell properties. We also obtained miRNA profiles of ESA+CD44+CD24-/low BCSCs. Most of the possible targets of potential tumorigenesis-related miRNAs were oncogenes, anti-oncogenes or regulatory genes.ConclusionsWe identified a subset of miRNAs that were differentially expressed in BCSCs, providing a starting point to explore the functions of these miRNAs. Evaluating characteristic BCSC miRNAs represents a new method for studying breast cancer-initiating cells and developing therapeutic strategies aimed at eradicating the tumorigenic subpopulation of cells in breast cancer.

Novel molecular beacons to monitor microRNAs in non-small-cell lung cancer.

Lung cancer is the leading cause of cancer death worldwide. There is no effective early diagnostic technology for lung cancer. microRNAs (miRNAs) are noncoding RNA molecules which regulate the process of cell growth and differentiation in human cancers. Hsa-miR-155 (miR-155), highly expressed in non-small-cell lung cancer (NSCLC), can be used as a diagnostic marker for NSCLC. Dynamic observation of miR-155 is critical to diagnose NSCLC. A novel molecular beacon (MB) of miR-155 was designed to image the expression of miR-155 in NSCLC. Then miR-155 was detected in vitro by laser confocal microscopy and in vivo by stereomicroscope imaging system, respectively. The present study demonstrated that intracellular miR-155 could be successfully and quickly detected by novel miR-155 MBs. As a noninvasive monitoring approach, MBs could be used to diagnose lung cancer at early stage through molecular imaging.

Increased treatment-related mortality with additional cisplatin-based chemotherapy in patients with nasopharyngeal carcinoma treated with standard radiotherapy

BACKGROUND AND PURPOSES We performed a meta-analysis of randomized controlled trials (RCTs) to determine the overall risk of treatment-related death associated with additional cisplatin-based chemotherapy in patients with nasopharyngeal carcinoma treated with standard radiotherapy. MATERIAL AND METHODS Eligible studies included RCTs in which cisplatin-based chemotherapy in combination with radiotherapy was compared with radiotherapy alone. Statistical analyses were conducted to calculate the summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effects models based on the heterogeneity of included studies. RESULTS A total of 2829 patients from 13 RCTs were included in this study. The overall incidence for treatment-related death in chemoradiotherapy and radiotherapy treated patients was 1.7% and 0.8%. Compared to radiotherapy alone, radiotherapy plus cisplatin-based chemotherapy significantly increased the risk of treatment-related mortality. On subgroup analyses, no difference was found in treatment-related mortality between different timings of chemotherapy and chemotherapeutic agents. Adding cisplatin-based chemotherapy was associated with higher incidences of severe acute toxicity. CONCLUSIONS Cisplatin-based chemotherapy plus radiotherapy increased the risk of treatment-related death and severe acute toxicity, compared with radiotherapy alone. Better management of treatment toxicity might improve the therapeutic gain in patients with nasopharyngeal carcinoma.

Role of inhibitor of apoptosis protein Livin in radiation resistance in nonsmall cell lung cancer.

OBJECTIVE The objective of the present study was to explore the role of the inhibitor of apoptosis protein (IAP) Livin in radioresistance in nonsmall cell lung cancer (NSCLC). METHODS Lung adenocarcinoma cell lines A549 and SPC-A1 were used for this study. Using the technique of molecular cloning and gene transfection, two Livin isoforms, Livinα and β, respectively, were expressed in A549 cells with the purpose of exploring the role of Livin in radiation resistance of A549 cells. Moreover, a Livin-specific gene-silencing system was developed using SPC-A1 cell line with the purpose of increasing radiosensitivity of SPC-A1 cells. RESULTS A549 cells were induced by radiation to express Livin isoforms, Livinα and β. A549 cells expressed Livin isoforms stably after gene transfection and the transfected cells demonstrated characteristics of antiradiation. However, Livin gene-silenced SPC-A1 cells exhibited remarkably enhanced radiation sensitivity. CONCLUSION The IAP Livin is an important molecule in antiradiotherapy of NSCLC. Livin-specific gene silencing is likely to be an effective means to enhance radiation sensitivity of lung cancer.

Identification of a Cancer Stem-like Population in the Lewis Lung Cancer Cell Line

OBJECTIVE Although various human cancer stem cells (CSCs) have been defined, their applications are restricted to immunocompromised models. Developing a novel CSC model which could be used in immunocompetent or transgenic mice is essential for further understanding of the biomolecular characteristics of tumor stem cells. Therefore, in this study, we analyzed murine lung cancer cells for the presence of CSCs. METHODS Side population (SP) cells were isolated by fluorescence activated cell sorting, followed by serum-free medium (SFM) culture, using Lewis lung carcinoma cell (LLC) line. The self-renewal, differentiated progeny, chemosensitivity, and tumorigenic properties in SP and non-SP cells were investigated through in vitro culture and in vivo serial transplantation. Differential expression profiles of stem cell markers were examined by RT-PCR. RESULTS The SP cell fraction comprised 1.1% of the total LLC population. SP cells were available to grow in SFM, and had significantly enhanced capacity for cell proliferation and colony formation. They were also more resistant to cisplatin in comparison to non-SP cells, and displayed increased tumorigenic ability. Moreover, SP cells showed higher mRNA expression of Oct-4, ABCG2, and CD44. CONCLUSION We identified SP cells from a murine lung carcinoma, which possess well-known characteristics of CSCs. Our study established a useful model that should allow investigation of the biological features and pharmacosensitivity of lung CSCs, both in vitro and in syngeneic immunocompetent or transgenic/knockout mice.

Efficacy and safety of endostar® combined with chemotherapy in patients with advanced soft tissue sarcomas.

BACKGROUND Soft tissue sarcomas (STS) are a heterogeneous group of tumors, and approximately 40-50% of patients with STS develop metastatic disease. The median overall survival of those patients was 12 months and their 5-year survival rate was 8%. Therefore, study on more effective treatment, especially the targeting therapies, is urgently needed. OBJECTIVE To evaluate the efficacy and safety of Endostar® combined with chemotherapy in patients with advanced STS. METHODS A retrospective case-series study was conducted in Cancer Institute of PLA, Xinqiao Hospital. A total of 71 patients suffering from advanced STS (IIB - IV) were included, of whom 49 cases treated with chemotherapy alone were defined as the control group and the rest 22 cases treated with the traditional chemotherapy combined with Endostar® were defined as the test group. The short-term therapeutic effects including objective response rate (ORR), disease control rate (DCR) and safety were evaluated in the two groups. In the follow-up, progression-free survival (PFS) and overall survival (OS) were also observed. RESULTS In the test and control groups, the ORR was 18.2% and 12.2%, respectively (P = 0.767), and the DCR was 86.4% and 61.2%, respectively (P=0.034). The median time to progression in the test and control groups was 120 days and 70 days with significant difference (P = 0.017), while the median overall survival was 452 days and 286 days without significant difference (P = 0.503). The one-year survival rate in the test group and control group was 56.2% and 35.4%, respectively, while the two-year survival rate was 30.2% and 26.5%, respectively. No significant difference in the side effects was found between the two groups. CONCLUSIONS Endostar® combined with chemotherapy resulted in a higher DCR and longer PFS in the patients with advanced STS, and the toxicity was tolerable.

Comparison of Total Body Irradiation Before and After Chemotherapy in Pretreatment for Hematopoietic Stem Cell Transplantation

OBJECTIVE To explore the best time to carry out total body irradiation (TBI) in hematopoietic stem cell transplantation (HSCT) pretreatment. METHODS Retrospective analysis was applied in 88 cases of HSCT using TBI as pretreatment from March 2001 to June 2009 in our hospital. Using 8 MV X-ray, all the patients were irradiated by linear accelerator in 2 consecutive days, with a total dose of 7-11 Gy and an instantaneous dose rate ranging between 4.0 and 5.0 cGy/min. Of the 88 cases, 40 cases were given traditional high-dose chemotherapy before TBI (Group CT/TBI), and 48 cases were given TBI before chemotherapy (Group TBI/CT) instead. RESULTS Eighty-seven cases of transplantation were successful, with no serious complications, including radiation pneumonia. Compared with Group CT/TBI, Group TBI/CT showed similar incidence of complications (p=0.08), similar recent chemotherapy toxicity (p=0.833), and significantly lower recent radiation toxicity (p=0.000). CONCLUSIONS TBI in the pretreatment of HSCT is safe and effective. Using TBI before the high-dose chemotherapy can maintain the same pretreatment effect, effectively reduce apparent immediate reaction/discomfort during TBI, reduce preparation workload of radiotherapy, and lower radiation side-effects. Further research is needed to expand its clinical application.