Background and Objective: Research has shown that 5-bromotetrandrine (BrTet) can effectively reverse multidrug resistance (MDR). Imatinib plays an important role in cell proliferation. This study explored the efficacy of the combination of imatinib and BrTet on reversing MDR of tumor cells and its mechanism. Methods: Cytoxicity was assessed by MTT assay. Apoptosis of K562/A02 cells was analyzed by flow cytometry. The expressions of mdr1 mRNA and P-glycoprotein (P-gp) were detected using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Results: After 48 h of treatment with 0.0625 umol/L imatinib, 0.5 umol/L BrTet, or both, the 50% inhibition concentration (IC50) of daunorubicin (DNR) for the K562/A02 cells were 5.69 mg/L, 5.41 mg/L, and 2.19 mg/L, respectively. The gray-scale values of mdr1 mRNA expression in the K562/A02 cells were 0.65 ± 0.02, 0.64 ± 0.01, and 0.25± 0.03, respectively. The expression levels of P-gp were 0.74 ± 0.02, 0.52 ± 0.02, and 0.29 ± 0.02, respectively. All decreased significantly in the K562/A02 cells treated with both imatinib and BrTet compared to cells treated with imatinib and BrTet alone (P < 0.05). The apoptosis rates of the K562/A02 cells increased without a significant difference after treatment with DNR, imatinib, or BrTet (P > 0.05), while increased significantly after treatment with DNR combined with imatinib, BrTet, or both (P < 0.05). Conclusions: The MDR of K562/A02 cells may be partially reversed by imatinib or BrTet, and the mechanism may be related to the downregulation of mdr1 mRNA and P-gp expression and the upregulation of the rate of apoptosis in K562/A02 cells. Imatinib combined with BrTet showed a synergistic effect on K562/A02 cells.
作者:陈宝安;单学赟;程坚;Guo-Hua Xia;Wen-Lin Xu;Michael Schmit 刊期: 2010年第06期
Background and Objective: Androgen receptor (AR) is involved in the pathogenesis of breast cancer, but its role is not clearly defined. This study was to explore the expression of AR and its relationship with clinicopathologic parameters in triple negative breast cancer (negative estrogen receptor, negative progesterone receptor, and negative Her-2). Methods: Immunohistochemical assays were performed to determine the expression of AR in 137 cases of triple negative breast cancer and 132 cases of non-triple negative breast cancer. The relationships between AR expression and clinicopathologic data and prognosis were analyzed. Results: The positive rate of AR was significantly lower in triple negative breast cancer than in non-triple negative breast (27.7% vs. 83.3%,χ2 = 83.963, P < 0.001). AR expression was correlated with menorrheal status (χ2 = 6.803, P = 0.009), tumor grade (χ2 = 5.173, P = 0.023), node status (χ2 = 7.787, P = 0.005), 5-year disease-free survival (χ2 = 5.012, P = 0.025) and 5-year overall survival (χ2 = 5.552, P = 0.018) in triple negative breast cancer, but was not correlated with clinicopathologic parameters and survival in non-triple negative breast cancer. The 5-year overall survival rate was 78.8% in triple negative breast cancer and 83.3% in non-triple negative breast cancer. Conclusions: The expression of AR is related to biological behaviors of triple negative breast cancer, and plays a role in endocrinotherapy and prognostic prediction.
作者:罗湘;史艳侠;李志铭;Wen-Qi Jiang 刊期: 2010年第06期
Background and Objective: Intravesical administration of Bacillus Calmette-Guerin (BCG) after transurethral resection is by far the most effective local therapy for superficial bladder cancer, the fifth most common cancer in the world. However, approximately one-third of patients fail to respond and most patients eventually relapse. In addition, there are pronounced side effects of BCG therapy, such as BCG sepsis and a high frequency of BCG-induced cystitis. This study established a novel immunotherapy through immobilization of streptavidin-tagged human IL-2 (SA-hlL-2) on the biotinylated mucosal surface of bladder wall. Methods: A mouse orthotopic model of MB49 bladder cancer was established by perfusing MB49 cells into mouse bladders. The SA-hlL-2 fusion protein was immobilized on the biotinylated mucosal surface of the bladder wall. Treatment began on day 1 after MB49 implantation, once every 3 days for 6 times. Immunohistochemical assay was performed to assess the persistence of SA-hlL-2 immobilized on the biotinylated mucosal surface of the bladder wall. The mice were monitored for tumor growth and survival. On day 60 after MB49 implantation, the SA-hlL-2-cured mice, which were found to have no hematuria or palpable tumors, were challenged with wild-type MB49 cells implanted into the pretreated bladder and monitored for survival. Results: SA-hlL-2 could be immobilized efficiently and durably on the bladder mucosal surface as long as 7 days. On day 60 after MB49 implantation, 9 out of 20 SA-hlL-2-treated mice survived, but all mice in PBS control group died. More importantly, 5 out of 9 tumor-free mice in the SA-hlL-2 group were protected against a second intravesical wild-type MB49 tumor challenge. Conclusions: SA-hlL-2 fusion protein could significantly inhibit tumor growth and extend the survival time in the orthotopic model of MB49 bladder cancer.
作者:黄鑫;余宏盛;陈忠;Jin-Long Li;Zhi-Ming Hu;Ji-Min Gao 刊期: 2010年第06期
Precisely locating tumors always proves to be difficult. To find a molecule that can specifically bind to tumor cells is the key. Recently, chlorotoxin (CTX) has been proved to be able to bind to many kinds of tumor cells. The CTX receptor on the cell surface has been demonstrated to be matrix metalloproteinase-2 (MMP-2). Many researchers have combined CTX with other molecules, including 131I, Cy5.5, iron oxide nanoparticles coated by polyethylene glycol (NP-PEG), and so on, and thus synthesized various types of probes that can be detected by y-camera, single photon emission computed tomography (SPECT) or magnetic resonance imaging (MRI). With these methods, the binding degree of CTX could be assessed. These studies demonstrated that CTX has a highly specific binding ability, high stability, and security. CTX could also inhibit or kill the tumor cells. A nonviral nanovector has been developed for gene therapy. As a result, it gradually develops into a new method of diagnosis and targeted therapy of tumors. This article reviews the current progress on CTX including the origin, chemical construction, the mechanism of binding with tumor cells, and the application to tumor imaging diagnosis and therapy.
作者:吴晓珊;翦新春;尹乒;Zhi-Jing He 刊期: 2010年第06期
Glioma derived from the neural ectoderm is the most common brain tumor and is of great damage to human health among all lethal tumors. Scientists have been trying their best to find new methods and develop new drugs to treat glioma in recent years. The animal glioma model is of great importance to the research. Researchers have developed many animal glioma models, like the rat and mouse model. Now we are trying to develop a new zebrafish glioma model, which has much more advantages and fewer disadvantages than the traditional models in regard to gene mutation, chemical induction, and xenografts. Establishing a glioma model in zebrafish is feasible and would be of great use to patients with this common brain tumor.
作者:李冬;彭扣;李艺;Ying Peng 刊期: 2010年第06期
Synovial sarcoma is a rare soft tissue sarcoma of the head and neck region involving the parapharyngeal space. The diagnosis of synovial sarcoma can be very challenging to the pathologists. We present a rare case of parapharyngeal synovial sarcoma in a young female patient who had a two-month history of left cervical intumescent mass at level II. The fine needle aspiration cytology of the mass was proved inconclusive. Transcervical excision of the mass was performed and the first case of parapharyngeal sarcoma was identified in our center by fluorescence in situ hybridization (FISH) technique. Repeat imaging revealed residual tumor. The patient successfully underwent a second excision of the residual tumor and 收稿日期: adjuvant radiotherapy.
作者: 刊期: 2010年第06期
Background and Objective: The planning dose distribution of intensity-modulated radiation therapy (IMRT) has to be verified before clinical implementation. The commonly used verification method is to measure the beam fluency at 0 degree (0°) gantry angle with a 2-dimensional (2D) detector array, but not the composite dose distribution of the real delivery in the planned gantry angles. This study was to investigate the angular dependence of a 2D diode array (2D array) and the feasibility of using it to verify the composite dose distribution of IMRT. Methods: Angular response of the central detector in the 2D array was measured for 6 MV X-ray, 10 cm × 10 cm field and 100 cm source axis distance (SAD) in different depths. With the beam incidence angle of 0°-60°, at intervals of 10°, and inherent buildup of the 2D array (2 g/cm2), the array was Irradiated and the readings of the central diode were compared with the measurement of thimble ionization chamber. Using a combined 30cm×30cm×30cm phantom which consisted of solid water slabs on top and underlying the 2D array, with the diode detectors placed at 8 g/cm2 depth, measurements were taken for beam angles of 0°-180° at intervals of 10° and compared with the calculation of treatment planning system (TPS) that pre-verified with ion chamber measuring. Results: Differences between the array detector and thimble chamber measurements were greater than 1% and 3.5% when the beam angle was larger than 30° and 60°, respectively. The measurements in the combined phantom were different from the calculation as high as 20% for 90° beam angle, 2% at 90°± 5° and less than 1% for all the other beam angles. Conclusions: The 2D diode array is capable of being used in composite dose verification of IMRT when the beam angles of 90°±5° and 270°± 5° are avoided.
作者:李齐林;邓小武;陈立新;Xiao-Yan Huang;Shao-Min Huang 刊期: 2010年第06期