Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

Q: Cullin1 is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex which ubiquitinates a broad range of proteins participating in biochemical events like cell-cycle progression, signal transduction, and transcription. Cullin1 is involved in the progression of several cancers, such as melanoma, breast cancer, and gastric cancer.', "To investigate the role of Cullin1 in the development of non-small-cell lung cancer (NSCLC), we examined the expression of Cullin1 in 8-paired fresh NSCLC tissues. We then constructed immunohistochemistry (IHC) on 114 paraffin-embedded slices and evaluated the correlation between Cullin1 expression and clinicopathologic variables, as well as patients' overall survival.", "We found that Cullin1 was highly expressed in NSCLC tissues and significantly associated with NSCLC's histological differentiation (P=0.002), clinical stage (P=0.010) and Ki-67 (P=0.021). Furthermore, we showed a strong correlation between high Cullin1 expression and worse overall survival rates in NSCLC patients (P<0.001). Cox regression analysis revealed that Cullin1 expression was an independent prognostic factor to predict 5-year patient outcome in NSCLC cancer (P=0.033).

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Q: Human hepatocellular carcinoma (HCC) heterogeneity promotes recurrence and resistance to therapies. Recent studies have reported that HCC may be derived not only from adult hepatocytes and hepatoblasts but also hepatic stem/progenitors. In this context, HepaRG cells may represent a suitable cellular model to study stem/progenitor cancer cells and the retrodifferentiation of tumor-derived hepatocyte-like cells. Indeed, they differentiate into hepatocyte- and biliary-like cells. Moreover, tumor-derived HepaRG hepatocyte-like cells (HepaRG-tdHep) differentiate into both hepatocyte- and biliary-like cells through a hepatic progenitor. In this study we report the mechanisms and molecular effectors involved in the retrodifferentiation of HepaRG-tdHep into bipotent progenitors. Gene expression profiling was used to identify genomic changes during the retrodifferentiation of HepaRG-tdHep into progenitors. We demonstrated that gene expression signatures related to a poor-prognosis HCC subclass, proliferative progenitors, or embryonic stem cells were significantly enriched in HepaRG progenitors derived from HepaRG-tdHep. HepaRG-tdHep retrodifferentiation is mediated by crosstalk between transforming growth factor beta 1 (TGFβ1) and inflammatory cytokine pathways (e.g., tumor necrosis factor alpha [TNFα] and interleukin 6 [IL6]). Signatures related to TNFα, IL6, and TGFβ activation pathways are induced within the first hour of retrodifferentiation. Moreover, specific activation or inhibition of these signaling pathways allowed us to determine that TNFα and IL6 contribute to the loss of hepatic-specific marker expression and that TGFβ1 induces an epithelial-to-mesenchymal transition of HepaRG-tdHep. Interestingly, the retrodifferentiation process is blocked by the histone deacetylase inhibitor trichostatin A, opening new therapeutic opportunities.

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Q: MiRNAs has been shown to be implicated in the pathogenesis of many human diseases including cancer. Dysregulation of miR-744 is common in a number of cancers, indicating miR-774 might be closely correlated with the tumorigenesis process. However, the role and clinical significance of miR-774 in nasopharyngeal carcinoma (NPC) is poorly known. Thus the aim of this study is to investigate whether there was any clinical value of serum miR-744 in detecting and predicting the prognosis of NPC.', 'Real-time PCR was used to examine the expression level of serum miR-744 in patients with NPC and the healthy volunteers. The changes in serum miR-744 expression level of NPC patients after receiving chemo-radiotherapy were also evaluated. The association between pre-treatment serum miR-744 expression level and NPC clinicopathological parameters was investigated. Finally we employed Kaplan-Meier method and Cox proportional hazards model to evaluate the clinical value of serum miR-744 in predicting the prognosis of NPC.', 'Our study showed the expression level of serum miR-744 was significant higher in patients with NPC in comparison with healthy controls (P<0.01). The serum miR-744 expression level was down-regulated significantly in NPC patients after receiving chemo-radiotherapy (P<0.01). The Pre-treatment Serum miR-744 expression level was correlated with various important NPC clinicopathological parameters including N stage, clinical stage and grade. In addition, NPC patients with higher serum miR-744 expression had poorer 5 year overall survival rate and relapse-free survival rate. What was more, serum miR-744 was showed to be an independent factor for predicting the prognosis of NPC.

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