Clinical factors affecting the long-term survival of breast cancer patients.

OBJECTIVE: The average 5-year survival rate of breast cancer (BC) patients has been significantly prolonged with new therapeutic methods. However, their effects on BC patient long-term survival rates are unclear. Therefore, this study aimed to analyze the specific clinical factors that can affect BC long-term survival. METHODS: Here, we conducted a retrospective study and analyzed long-term survival using data of 3,240 BC patients from 1977 to 2005 from the Genotype-Tissue Expression (GTEx) database using the Kaplan-Meier method. RESULTS: Breast tumor size and stage were negatively correlated with long-term survival, but age showed no significant correlation. Estrogen receptor (ER) and progesterone receptor (PR) expression were each positively correlated with patient survival time, while ERBB2 receptor (HER2) expression was negatively correlated with survival time. Patients with high Nottingham prognostic index (NPI) values did not benefit from available therapies. Furthermore, breast-conserving surgery is more conducive to BC patient long-term survival than mastectomy. CONCLUSIONS: Early detection and breast-conserving surgery may support long-term survival for BC patients. Elevated expression of ER and PR were both associated with longer patient survival time, while positive expression of HER2 showed the opposite trend. The long-term survival rates of patients with high NPI values can potentially be increased.

Gene expression profiling of brain metastatic cell from triple negative breast cancer: Understanding the molecular events.

Brain metastatic triple negative breast cancer (BM-TNBC) is afflicted with unfavorable prognosis. However, the molecular events underlying BM-TNBC remain largely unknown. In the present study, we conducted gene expression microarray analysis using the triple negative breast cancer cell line MDA-MB-231 and its brain metastatic derivative (MDA-MB-231Brm). Results of microarray analysis showed that a total of 4296 genes were differentially expressed, of which 2433 genes were up-regulated and 1863 genes were down-regulated. Gene Ontology (GO), KEGG pathway and protein-protein interaction (PPI) analyses indicated differentially expressed genes functionally categorized as genes of signal transduction, multicellular organismal development, ion transport, nervous system development, plasma membrane, extracellular region, calcium ion binding, GTP binding neuroactive ligand-receptor interaction. The validity of the microarray results was verified by quantitative real-time PCR analysis of twelve representative genes. The present findings revealed molecular basis and events associated with brain metastasis in TNBC, which will potentially contribute to the understanding of underlying mechanism and develop therapeutic targets.

The ratio of red cell distribution width to mean corpuscular volume in patients with diabetic ketoacidosis.

BACKGROUND: The relationship between erythrocyte parameters and diabetic ketoacidosis (DKA) remains uncertain. This study aimed to investigate the potential role of erythrocyte indices in type 1 diabetes (T1D) patients with DKA. METHODS: This study included 48 patients with T1D, 26 patients with DKA, and 30 age- and gender-matched controls. Erythrocyte parameters were measured and evaluated at the time of admission and after treatment. RESULTS: Data were analyzed by One-Way ANOVA Tukey analysis with SPSS software. The DKA patients had higher levels of plasma glucose (28.87 +/- 9.01 mmol/L), HbA1c (13.08 +/- 3.10%), osmotic pressure (332.11 +/- 11.67 mosm/L), red cell distribution width (RDW, 41.24 +/- 3.08 fL), and the RDW to mean corpuscular volume (MCV) ratio (47.50 +/- 3.70%) compared to non-DKA cases and controls (all p < 0.05). Pearson's correlation test showed that osmolality was positively correlated with plasma glucose (r = 0.699, p < 0.001) and negatively correlated with mean corpuscular hemoglobin concentration (MCHC) (r = -0.409, p = 0.049). Receiver operating characteristic curve analyses demonstrated that the areas under the curves were 0.924 for the RDW/MCV ratio and 0.802 for RDW in the ability of reflecting DKA (z = 2.086, p = 0.0369). A logistic regression revealed that the RDW/MCV ratio can act as a robust risk marker for the presence of DKA (OR = 1.548, p = 0.0360, 95% CI: 1.029 - 2.330). The RDW returned to normal, and plasma glucose levels and metabolic acidosis were well controlled following treatment. CONCLUSIONS: The RDW and the RDW/MCV ratio were significantly correlated with DKA. The RDW/MCV ratio can act as a robust biomarker that is more sensitive than RDW in reflecting the presence of DKA.

[Multispectral remote sensing image denoising based on non-local means].

The non-local mean denoising (NLM) exploits the fact that similar neighborhoods can occur anywhere in the image and can contribute to denoising. However, these current NLM methods do not aim at multichannel remote sensing image. Smoothing every band image separately will seriously damage the spectral information of the multispectral image. Then the authors promote the NLM from two aspects. Firstly, for multispectral image denoising, a weight value should be related to all channels but not only one channel. So for the kth band image, the authors use sum of smoothing kernel in all bands instead of one band. Secondly, for the patch whose spectral feature is similar to the spectral feature of the central patch, its weight should be larger. Bringing the two changes into the traditional non-local mean, a new multispectral non-local mean denoising method is proposed. In the experiments, different satellite images containing both urban and rural parts are used. For better evaluating the performance of the different method, ERGAS and SAM as quality index are used. And some other methods are compared with the proposed method. The proposed method shows better performance not only in ERGAS but also in SAM. Especially the spectral feature is better reserved in proposed NLM denoising.

[An improved physical model to correct topographic effects in remotely sensed imagery].

Topographic correction for remotely sensed imagery is an important preprocessing step in order to improve the retrieval accuracy of land surface spectral reflectance in mountainous area. Various kinds of topographic correction models have been proposed in the literature. Each model has its advantages and limitations. In consideration of the limitations of the topographic correction models in the literature, an improved Shepherd topographic correction model is proposed in this paper. Diffuse irradiance is an essential factor in the physically based topographic correction model. While in the Shepherd model (originally proposed by Shepherd et al. in 2003), accuracy of the method to compute the diffuse irradiance is relatively low; therefore, the accuracy of the land surface spectral reflectance retrieved with the Shepherd model is impacted. In order to improve the accuracy of diffuse irradiance, hence the accuracy of land surface spectral reflectance, a different method (named the Perez model), is used to obtain the diffuse irradiance with higher accuracy in the improved Shepherd model. Landsat 5 Thematic Mapper (TM) imagery acquired on July 12th 2006, over the mountainous areas in the north of Beijing city, was employed to retrieve land surface spectral reflectance with the improved Shepherd topographic correction model and 6S (Second Simulation of the Satellite Signal in the Solar Spectrum) atmospheric radiative transfer model. Correction results were tested with three different methods. Testing result shows that the improved Shepherd topographic correction model can achieve a good correction result and is better than Shepherd and C topographic correction model. What is more, this improved model is physically based and can be applied to all kinds of optical satellite imagery.

[Influence of celecoxib combined with IFN-alpha on proliferation, apoptosis, cell cycle and CD117 expression of K562 cells].

The aim of this study was to investigate the effects of Celecoxib on the proliferation, apoptosis, cell cycle and CD117 expression of K562 cells, and to explore its synergistic effect with IFN-alpha. K562 cells were treated with IFN-alpha, Celecoxib and combination of Celecoxib with IFN-alpha at different concentrations. The inhibitory effect of Celecoxib and IFN-alpha on cell proliferation was detected with MTT assay, the cell apoptosis, cell cycle and CD117 expression were determined by morphology observation and flow cytometry. The results showed that the Celecoxib inhibited proliferation of K562 cells in concentration-dependent manner (r=-0.91). After culture of K562 cells for 72 hours, the rates of K562 cell proliferation in control group, IFN-alpha group, Celecoxib group and IFN-alpha-combined Celecoxib group were (96.1+/-0.5)%, (90.2+/-0.4)%, (57.2+/-0.9)% and (21.9+/-0.3)% respectively. The cell apoptosis rates in 4 groups were (5.5+/-0.8)%, (6.3+/-0.6)%, (26.4+/-3.9)% and (57.3+/-4.5)% respectively. The CD117 expression rates in 4 groups were 54.7%, 10.5%, 36.3% and 7.3% respectively. Combination of Celecoxib with IFN-alpha might block K562 cells in G0/G1 phase. In conclusion, Celecoxib and IFN-alpha both may inhibit K562 cell proliferation, induce apoptosis, reduce CD117 expression and produce G0/G1 phase block to various degree and the two drugs have a synergistic effect.

[Short term high-dose dexamethasone therapy in previously untreated idiopathic thrombocytopenic purpura].

OBJECTIVE: To observe the long-term effect of short interim high-dose dexamethasone (HD-DXM)in previously untreated patients affected by idiopathic thrombocytopenic purpura(ITP) and investigate the action of maintenance treatment. METHODS: 40 mg/d of dexamethasone was given in a 4-day pulse every 14 days for 3 cycles to 45 patients with ITP. Among them, 22 cases were given routinely dexamethasone of 0.035 mg x kg(-1) x d(-1) for maintenance treatment between courses of high-dose dexamethasone (HD-DXM + RM group)and 23 cases were given dexamethasone of 0.035 mg x kg(-1) x d(-1) only when the platelet count was lower than 20 x 10(9)/L (HD-DXM + SM group). As a control group, another 22 cases were given routine dosage of prednisone (control group). RESULTS: (1) At the end of the third cycle, the effective rate in the HD-DXM + RM group was 81.8% (18/22), which was higher than 65.2% (15/23) of the HD-DXM + SM group and 63.6% (14/22) of the control group. (2) Among the HD-DXM group patients, the effective rate at the end of the third cycle was higher than that at the end of first and second cycles. (3) The effective rate of HD-DXM + RM group was higher than that of HD-DXM + SM group. (4) At the time of 1, 2, 3, and 4 months after the end of the last cycle of HD-DXM, the relapse rates in HD-DXM + RM group were 16.7%, 16.7%, 27.8% and 33.3% respectively, which were lower than that of HD-DXM + SM group and control group respectively. CONCLUSIONS: A schedule of 3 cycles of HD-DXM pulses with an interval of 2 weeks between cycles is an effective method for previously untreated ITP patients and maintenance treatment with small-dose dexamethasone between high-dose dexamethasone contributes to improve the long-term curative effect.

Antitumor effects of celecoxib on K562 leukemia cells are mediated by cell-cycle arrest, caspase-3 activation, and downregulation of Cox-2 expression and are synergistic with hydroxyurea or imatinib.

Celecoxib, a specific cyclooxygenase-2 (Cox-2) inhibitor, has been shown to possess antitumor activity in a variety of cancer cells. However, the antitumor activity of celecoxib in hematopoietic tumors, especially in chronic myeloid leukemia (CML), has not been well established. This study was designed to investigate the effect of celecoxib on growth and apoptosis in a human CML cell line (K562 cells) or in primary CML cells, and to examine the synergistic actions of celecoxib and hydroxyurea or imatinib on K562 cell proliferation and apoptosis. Celecoxib significantly inhibited the growth of both K562 and primary CML cells and induced apoptosis in a dose-dependent fashion. The IC50 of celecoxib was 46 microM for inhibition of K562 cell proliferation. The effect of celecoxib on growth inhibition was accompanied by the downregulation of cyclin D1 and cyclin E and p-Rb expression, the upregulation of P16(INK4a) and P27KIP expression, and a G1-S phase arrest of the cell cycle. The pro-apoptotic effect of celecoxib was determined to be mediated by caspase-3 activation. When K562 cells were pretreated with DEVD-fmk, a specific inhibitor of caspases, the apoptotic activity of celecoxib was, in part, abrogated. Importantly, we demonstrated for the first time that K562 cells were Cox-2-positive both at the mRNA and protein levels. We noted the following observations: (i) we detected Cox-2 mRNA in K562 cells by reverse transcription-PCR (RT-PCR) and protein expression by western blot analysis; (ii) Cox-2 expression in K562 cells was stimulated by IL-1beta, a specific inducing agent of Cox-2 expression; (iii) primary CML cells from CML patient bone marrow also exhibited Cox-2 protein expression. Furthermore, Cox-2 expression was downregulated at higher doses of celecoxib (80-160 microM), suggesting a Cox-2-dependent mechanism was involved in the drug's effects of growth inhibition and induction of apoptosis. In addition, a synergistic effect was observed when cells were exposed to low-dose celecoxib (40 microM) and hydroxyurea (10 mM) or a combination of celecoxib (40 microM) and imatinib (0.2 microM). These findings provide the basis for uncovering the mechanism of celecoxib's antitumor effects and developing a new therapeutic strategy for treating CML.

[Effect of celecoxib on enhancing the chemotherapic sensitivity of hydroxyurea to K562 cells and its mechanism].

OBJECTIVE: To determine whether celecoxib can enhance the anti-proliferative effect of hydroxyurea on K562 cells and to reveal its molecular mechanism. METHODS: K562 cells were treated with low dose celecoxib (40 micromol/L) or hydroxyurea (10 mmol/L) and celecoxib (40 micromol/L) combined with hydroxyurea (10 mmol/L) for 36 h. The effects of the drugs on K562 cell growth inhibitation, apoptosis inducement and its molecular mechanism were analyzed by MTT assay, DNA fragment analysis, Western blotting, and RT-PCR. RESULTS: The treatment of celecoxib (40 micromol/L) combined with hydroxyurea (10 mmol/L) could significantly inhibit the K562 cell viability and induce the K562 cell apoptosis than those treatments of celecoxib or hydroxyurea alone. The combination of celecoxib and hydroxyurea could evidently inhibit the expression of COX-2 protein or COX-2 mRNA of K562 cells. CONCLUSION: Celecoxib can enhance the anti-proliferative effect of hydroxyurea on K562 cells, which is associated with the down-regulation of both COX-2 protein and COX-2 mRNA on K562 cells.

[Indomethacin-induced HL-60 leukemic cell apoptosis and the activation of C-jun NH2- terminal kinase signal transduction pathway].

OBJECTIVE: To observe the effect of indomethacin on inhibiting the proliferation of HL-60 cells and inducing HL-60 cells apoptosis and to explore the activation of C-Jun NH2-terminal kinase (JNK) signal transduction pathway in mediating indomethacin-induced HL-60 cell apoptosis. METHODS: The cell viability was determined by Trypan blue staining and the state of cell proliferation was analyzed; DNA ladder pattern and AO/EB staining were applied to identify the cell apoptosis; the apoptotic signal proteins including caspase-9, caspase-3, and PARP and the proteins of JNK signal pathway such as MEK4, JNK, P-JNK, and P-C-Jun, were detected by Western blotting. RESULTS: Indomethacin at 200 to approximately 400 micromol significantly inhibited the proliferation of HL-60 cells and induced the cell apoptosis in a time- or concentration-dependent manner; caspase-9, caspase-3, and PARP were cleaved and activated in undergoing apoptotic cells; and the expressions of MEK4, P-JNK, and P-C-Jun were upregulated with the increase of indomethacin concentration. CONCLUSION: Indomethacin can inhibit the proliferation of HL-60 cell and induce leukemic cell apoptosis. The activation of JNK signal transduction pathway mediates the event of indomethacin-induced HL-60 cell apoptosis. JNK signal pathway is located in the upstream of caspase signal pathway.