Dose pre-hospital laryngeal mask airway use has a survival benefit in non-shockable cardiac arrest?

Background. Whether pre-hospital laryngeal mask airway (LMA) use poses a survival benefit and should be approved as routine airway management in non-shockable cardiac arrest is of major concern. The present study examined the effectiveness of LMA, in comparison to other pre-hospital airway management on individuals who have experienced non-shockable cardiac arrest. Methods. Adult patients who experienced non-shockable cardiac arrest with activation of the emergency medical service (EMS) made up our study cohort in Taoyuan, Taiwan. The data were abstracted from EMS records and cardiac arrest registration protocols. Results. Among the 1912 enrolled patients, most received LMA insertion (72.4%), 108 (5.6%) bag-valve-mask (BVM) ventilation, 376 (19.7%) high-flow oxygen non-rebreather facemask, and only 44 (2.3%) received endotracheal tube intubation (ETI). With regard to survival to discharge, no significant differences in prevalence were evident among the groups: 2.8% of oxygen facial mask, 1.1% of BVM, 2.1% of LMA, and 4.5% of the ETI group survived to discharge (p = 0.314). In comparison to oxygen facial mask use, different types of airway management remained unassociated with survival to discharge after adjusting for variables by logistic regression analysis (BVM: 95% confidence interval [CI], 0.079 – 1.639 [p = 0.186]; LMA: 95% CI, 0.220–2.487 [p = 0.627]; ETI: 95% CI, 0.325–17.820 [p = 0.390]). The results of Hosmer-Lemeshow goodness-of-fit test of logistic regression model revealed good calibration. Conclusions. Pre-hospital LMA use was not associated with additional survival to discharge compared with facial oxygen mask, BVM, or ETI following non-shockable cardiac arrest

The p53-dependent apoptotic pathway of breast cancer cells (BC-M1) induced by the bis-type bioreductive compound aziridinylnaphthoquinone

INTRODUCTION: Several aziridinylbenzoquinone drugs have undergone clinical trials as potential antitumor drugs. These bioreductive compounds are designed to kill cells preferentially within the hypoxia tumor microenvironment. The bioreductive compound of bis-type naphthoquinone synthesized in our laboratory, 2-aziridin-1-yl-3-[(2-{2-[(3-aziridin-1-yl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)thio]ethoxy}ethyl)thio]naphthoquinone (AZ-1), had the most potent death effect on the breast cancer cells BC-M1 in our previous screening. In the present study, we determined that the mechanism of the death effect of BC-M1 cells induced by AZ-1 was mediated by the apoptosis pathway. METHODS: We evaluated the cytotoxicity of AZ-1 and the anti-breast cancer drugs tamoxifen and paclitaxel to BC-M1 cells and MCF-7 cells by the MTT assay and measured the apoptosis phenomena by Hoechst 33258 staining for apoptotic bodies. We also quantified the sub-G(1 )peak area and the ratio of the CH(2)/CH(3 )peak area of the cell membrane in BC-M1 cells by flow cytometry and (1)H-NMR spectra, respectively. The apoptosis-related protein expressions, including p53, p21, the RNA-relating protein T-cell restricted intracellular antigen-related protein, cyclin-dependent kinase 2 (cell cycle regulating kinase) and pro-caspase 3, were detected by western blot, and the caspase-3 enzyme activity was also quantified by an assay kit. RESULTS: AZ-1 induced two of the breast cancer cell lines, with IC(50 )= 0.51 μM in BC-M1 cells and with IC(50)= 0.57 μM in MCF-7 cells, and showed less cytotoxicity to normal fibroblast cells (skin fibroblasts) with IC(50)= 5.6 μM. There was a 10-fold difference between two breast cancer cell lines and normal fibroblasts. Of the two anti-breast cancer drugs, tamoxifen showed IC(50)= 0.12 μM to BC-M1 cells and paclitaxel had much less sensitivity than AZ-1. The expression of p53 protein increased from 0.5 to 1.0 μM AZ-1 and decreased at 2.0 μM AZ-1. The p21 protein increased from 0.5 μM AZ-1, with the highest at 2 μM AZ-1. Regarding the AZ-1 compound-induced BC-M1 cells mediating the apoptosis pathway, the apoptotic body formation, the sub-G(1 )peak area, the ratio of CH(2)/CH(3 )of phospholipids in the cell membrane and the enzyme activity of caspase-3 were all in direct proportion with the dose-dependent increase of the concentration of AZ-1. The death effect-related proteins, including T-cell restricted intracellular antigen-related protein, cyclin-dependent kinase 2, and pro-caspase-3, all dose-dependently decreased with AZ-1 concentration. CONCLUSIONS: The AZ-1-induced cell death of BC-M1 cells mediating the apoptosis pathway might be associated with p53 protein expression, and AZ-1 could have the chance to be a candidate drug for anti-breast cancer following more experimental evidence, such as animal models

Validation of bidimensional measurement in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Our previous study showed a close relationship between computed tomography (CT)-derived bidimensional measurement of primary tumor and retropharyngeal nodes (BDMprn) and gross tumor volume of primary tumor and retropharyngeal nodes (GTVprn) in nasopharyngeal carcinoma (NPC) and better prognosis for NPC patients with smaller BDMprn. In this study, we report the results on of a study to validate the use of BDM in a separate cohort of NPC patients.</p> <p>Methods</p> <p>We retrospectively reviewed 103 newly diagnosed NPC cases who were treated with radiotherapy/concurrent chemoradiotherapy (CCRT) or CCRT with adjuvant chemotherapy from 2002 to 2009. We used magnetic resonance imaging (MRI) to measure BDMprn. We calculated overall survival, recurrence-free and distant metastasis-free survival curves and set a BDMprn cut off point to categorize patients into a high- or low-risk group. We then used Cox proportional hazard model to evaluate the prognostic influence of BDMprn after correcting age, gender and chemotherapy status.</p> <p>Results</p> <p>After adjusting for age, gender, and chemotherapy status, BDMprn remained an independent prognostic factor for distant metastasis [Hazard ratio (HR) = 1.046; <it>P </it>= 0.042] and overall survival (HR = 1.012; <it>P </it>= 0.012). Patients with BDMprn < 15 cm²had a greater 3-year overall survival rate than those with BDMprn ≧ 15 cm²(92.3% vs. 73.7%; <it>P </it>= 0.009). They also had a greater 3-year distant metastasis-free survival (94% vs.75%; <it>P </it>= 0.034).</p> <p>Conclusion</p> <p>The predictive ability of BDMprn was validated in a separate NPC cohort. A BDMprn of 15 cm²can be used to separate NPC patients into high- and low-risk groups and predict survival rates and metastasis potential. It can, therefore, be used as a reference to design clinical trials, predict prognosis, and make treatment decisions.</p

The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer: An In Vitro and In Vivo Comparison Study with Herceptin

HER-2 is an important oncoprotein overexpressed in about 15–25% of breast cancers. We hypothesized that the ability of curcumin to downregulate HER-2 oncoprotein and inhibit the signal transduction pathway of PI3K/Akt, MAPK, and NF-κB activation may be important in the treatment of HER-2-overexpressed breast cancer. To examine the effect of curcumin on breast cancer cells, MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr (a herceptin resistant strain from SK-BR-3) cells were used for in vitro analysis. The in vivo effect of curcumin on HER-2-overexpressed breast cancer was investigated with the HER-2-overexpressed BT-474 xenograft model. Cell growth, cell cycle change, the antimobility effect, signal transduction, and xenograft volume analysis between groups treated with herceptin and/or curcumin were tested. Curcumin decreased the cell growth of various breast cancer cell lines (MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr). In Western blot analysis, the phosphorylation of Akt, MAPK, and expression of NF-κB were reduced in BT-474 cells, but not in SK-BR-3-hr cells, after treatment with herceptin. When treated with curcumin, the HER-2 oncoprotein, phosphorylation of Akt, MAPK and expression of NF-κB were decreased in both BT-474 and SK-BR-3-hr cells. In the BT-474 xenograft model, though not as much as herceptin, curcumin did effectively decrease the tumor size. The combination of curcumin with herceptin was not better than herceptin alone; however, the combination of taxol and curcumin had an antitumor effect comparable with taxol and herceptin. The results suggested that curcumin has potential as a treatment for HER-2-overexpressed breast cancer

Effect of Supplementation of Tanshinone IIA and Sodium Tanshinone IIA Sulfonate on the Anticancer Effect of Epirubicin: An In Vitro Study

Tanshinone IIA (Tan IIA) and sodium tanshinone IIA sulfonate (STS) were found to have protective effects on cardiomyocyte against adriamycin-induced damage and may be used clinically. It is unclear whether the supplementation of STS or Tan IIA would affect the anticancer activity of anthracycline. To evaluate the effect of Tan IIA or STS on the anticancer of epirubicin, the cell viability, apoptosis, Akt expression, and uptake of epirubicin after supplementation of Tan IIA or STS in the epirubicin-treated BT-20 cells were measured and compared. Tan IIA inhibited BT-20 cell growth and induced apoptosis in a time- and dose-dependent manner. When Tan IIA was used with epirubicin, an increase of BT-20 cells apoptosis was accompanied by the decreasing phosphorylation of Akt. STS had no effect on the cell viability of BT-20 cells. However, when used with epirubicin, STS decreased the epirubicin-induced cytotoxicity and apoptosis in BT-20 cells. The antagonistic effect of STS on epirubicin-induced cytotoxicity in BT-20 cells occurred concomitantly with the reduced epirubicin uptake and the increased phosphorylation of Akt. STS decreased the uptake of epirubicin in BT-20 cells and blocked epirubicin-induced apoptosis through activation of Akt