TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: An intact and fully functional multiprotein DNA replication complex (DNA synthesome) from human as well as from murine mammary carcinoma cells was first isolated and characterized in our laboratory. The human cell synthesome supports the in vitro origin-specific simian virus 40 (SV40) DNA replication reaction in the presence of the viral large T-antigen using a semiconservative mechanism and has been shown to contain all the proteins and enzymes required to support DNA synthesis. We are currently using the DNA synthesome as a unique model for analyzing the mechanism of action of anticancer drugs affecting DNA replication. The purpose of this study was to further investigate the mechanism of action of ara-C using the DNA synthesome isolated from the human breast cancer cell line MDA MB-468.', 'Synthesome-mediated SV40 DNA replication was performed in the presence of various concentrations of ara-CTP (the active metabolite of ara-C) and the types of daughter DNA molecules produced were analyzed lusing neutral and alkaline gel electrophoresis. We also examined the effect of ara-C on intact MDA MB-468 cell DNA synthesis and on cell proliferation. In addition, we studied the effect of ara-CTP on the activity of some of the synthesome target proteins (the DNA polymerases alpha and delta).', 'Full-length daughter DNA molecules were obtained in the presence of low concentrations of ara-CTP while at higher concentrations, there was an inhibition of full-length daughter DNA synthesis. The findings suggest that specifically the initiation phase of DNA synthesis was inhibited by ara-CTP since the production of the short Okazaki fragments was suppressed at all concentrations of the drug above 10 microM. In addition, it was found that the IC50 of ara-CTP for inhibition of synthesome-mediated in vitro DNA replication was comparable to that required to inhibit intact cell DNA synthesis. Further experimentation has shown that ara-CTP preferentially inhibits the activity of the synthesome-associated DNA polymerase alpha enzyme while the DNA polymerase delta seems to be resistant to the inhibitory effect of that drug.\Question: Does ara-C affect formation of cancer cell DNA synthesome replication intermediates?

SOLUTION: Our results indicate that ara-C's action on DNA replication is mediated primarily through DNA polymerase alpha and suggest that this enzyme plays a key role in DNA synthetic initiation events. The results also provide definitive support for the use of the DNA synthesome as a unique and powerful model for analyzing the mechanism of action of anticancer drugs which directly affect DNA replication.

PROBLEM: Context: Previous studies have shown that Astragalus polysaccharide (APS) can be applied to anti-cancer. However, the mechanism by which APS mediate this effect is unclear. In the present study, APS-mediated NSCLC cell apoptosis was investigated through the regulation of the notch signaling pathway.', 'The cell viability was detected by the CCK8 assay. The mRNA and protein expression of notch1/3 and tumor suppressors were analyzed by RT-PCR and western blotting, respectively.', 'The mRNA and protein of notch1 and notch3 were significantly up-regulated in tumor tissues as compared to non-tumor adjacent tissues. Treatment of human NSCLC cells with APS induced cell death in a dose-and time-dependent manner by using CCK8 assay. The mRNA and protein expression of notch1 and notch3 were significantly lower in NSCLC cells with APS treatment than that in control group. Moreover, western blotting analysis showed that treatment of H460 cells with APS significantly increased the pro-apoptotic Bax and caspase 8 levels, decreased the anti-apoptotic Bcl-2 level. Furthermore, p53, p21 and p16 were obviously up-regulated by APS treatment in H460 cell.\Question: Are notch1/3 and p53/p21 a potential therapeutic target for APS-induced apoptosis in non-small cell lung carcinoma cell lines?

SOLUTION: This study demonstrated that APS-treated could inhibit proliferation and promote cell apoptosis, at least partially, through suppressing the expression of notch1 and notch3 and up-regulating the expression of tumor suppressors in H460 NSCLC cell lines.

PROBLEM: Context: Acute nonvariceal upper-GI hemorrhage (NVUGIH) is associated with significant morbidity and mortality.', 'To examine the relationship between hospital volume and outcomes of NVUGIH.', 'A cross-sectional study.', 'Participating hospitals from the Nationwide Inpatient Sample 2004.', 'All discharged patients with a primary discharge diagnosis of NVUGIH based on the International Classification of Diseases, Clinical Modification, ninth edition codes.', 'Patients were divided into 3 groups based on discharge from hospitals with annual discharge volumes of 1 to 125 (low), 126 to 250 (medium), and >250 (high).', 'In-hospital mortality, length of stay, and hospitalization charges.', 'The study included a total of 135,366, 132,746, and 123,007 discharges with NVUGIH occurred from low-volume, medium-volume, and high-volume hospitals, respectively. On multivariate analysis, when adjusting for age, comorbidity, and the presence of complications, patients at high-volume hospitals had significantly lower in-hospital mortality (odds ratio [OR] 0.85 [95% CI, 0.74-0.98]) than patients at low-volume hospitals. Patients at high-volume hospitals were also more likely to undergo upper-GI endoscopy (OR 1.52 [95% CI, 1.36-1.69]) or early endoscopy within 1 day of hospitalization compared with low-volume hospitals (60.5% vs 53.8%, adjusted OR 1.28 [95% CI, 1.02-1.61]). Undergoing endoscopy within day 1 was associated with shorter hospital stays (-1.08 days [95% CI, -1.24 to -0.92 days]) and lower hospitalization charges (-$1958 [95% CI, -$3227 to -$688]).\Question: Is higher hospital volume associated with lower mortality in acute nonvariceal upper-GI hemorrhage?

SOLUTION:
The study was based on an administrative data set.