Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Input: Consider Input: Context: We utilized whole-genome mapping of promoters that are activated by DNA hypomethylation in hepatocellular carcinoma (HCC) clinical samples to shortlist novel targets for anticancer therapeutics. We provide a proof of principle of this approach by testing six genes short-listed in our screen for their essential role in cancer growth and invasiveness.', 'We used siRNA- or shRNA-mediated depletion to determine whether inhibition of these genes would reduce human tumor xenograft growth in mice as well as cell viability, anchorage-independent growth, invasive capacities, and state of activity of nodal signaling pathways in liver, breast, and bladder cancer cell lines.', 'Depletion of EXOSC4, RNMT, SENP6, WBSCR22, RASAL2, and NENF effectively and specifically inhibits cancer cell growth and cell invasive capacities in different types of cancer, but, remarkably, there is no effect on normal cell growth, suggesting a ubiquitous causal role for these genes in driving cancer growth and metastasis. Depletion of RASAL2 and NENF in vitro reduces their growth as explants in vivo in mice. RASAL2 and NENF depletion interferes with AKT, WNT, and MAPK signaling pathways as well as regulation of epigenetic proteins that were previously demonstrated to drive cancer growth and metastasis.
Answer: Our results prove that genes that are hypomethylated and induced in tumors are candidate targets for anticancer therapeutics in multiple cancer cell types. Because these genes are particularly activated in cancer, they constitute a group of targets for specific pharmacologic inhibitors of cancer and cancer metastasis. Clin Cancer Res; 20(12); 3118-32. ©2014 AACR.

Output: Does genome-wide study of hypomethylated and induced genes in patients with liver cancer unravel novel anticancer targets?


Input: Consider Input: Context: Evidence suggests that induction of heme oxygenase-1 (HO-1) inhibits proliferation of vascular smooth muscle cells and intimal thickening after arterial injury, and therapeutic molecules induce HO-1. Probucol is the only oral drug that inhibits restenosis in humans and intimal thickening in animals, although its underlying mechanism remains unclear.', 'Aortas were harvested from New Zealand White rabbits fed normal or 0.75% (wt/wt) probucol-fortified chow, with or without endothelial denudation of the abdominal aorta on day 21, and analyzed for heme oxygenase and apoptosis. Uninjured aortas were harvested on day 21 and balloon-injured aortas on days 22 and 25. Probucol significantly increased mRNA of HO-1 assessed by real-time PCR and HO activity in aortas at all time points. Probucol also enhanced apoptosis of medial cells in the injured aorta, as evidenced by the TUNEL assay. Furthermore, probucol (100 micromol/L) increased HO-1 mRNA and HO activity when added to rabbit aortic smooth muscle cells (RASMCs) cultured in serum-free medium for 24 hours. Induction of HO-1 mRNA was inhibited by actinomycin D and was associated with inhibition of RASMC proliferation. This probucol-induced increase in HO-1 mRNA and inhibition of RASMC proliferation was prevented by the HO inhibitor Sn(IV) protoporphyrin or transfection with small interference RNA (siRNA) to knockdown HO-1, but not by inactive Cu(II) protoporphyrin or scrambled siRNA.
Answer: Probucol induces HO-1, and this contributes to the inhibition of vascular SMC proliferation. This novel finding may explain how probucol inhibits restenosis and highlights HO-1 as a target for therapeutic intervention against occlusive vascular disease.

Output: Does probucol protect against smooth muscle cell proliferation by upregulating heme oxygenase-1?


Input: Consider Input: Context: Overweight/obesity is known to increase the risk of developing renal cell carcinoma (RCC). However, data on the prognostic impact of overweight in RCC is still conflicting. We assessed whether different body mass index (BMI) levels at the time of surgery had an effect on the long-term prognosis of RCC patients.', "We evaluated 771 patients, with complete information about their BMI, who had undergone renal surgery for RCC between 1990 and 2005 at the authors' institution; the mean follow-up was 5.48 years.", 'Underweight, normal weight, pre-obesity, and obesity were diagnosed in 4 (0.5%), 239 (31%), 356 (46.2%), and 172 (22.3%) RCC patients, respectively. Overweight (BMI >25) was significantly associated with younger age (P = 0.004) and positive nodal status (P = 0.04) but not with tumor stage, grade, visceral metastasis, gender, histological subtype, or tumor-related symptoms. Overweight patients had a significantly lower risk of cancer-related death; their median 5-year tumor-specific survival rate was 80% as opposed to 72% for patients with a BMI below 25 (P = 0.003). Interestingly, subgroup analysis revealed that the positive association between overweight and survival was even more pronounced in organ-confined (P < 0.001) RCC, but no correlation was observed in advanced disease (P = 0.23).
Answer: We were able to identify overweight as an independent prognostic marker of improved tumor-specific survival in patients with organ-confined RCC. Basic research is required to resolve the dilemma of why, if a higher BMI predisposes to RCC, it concurrently prolongs survival after patients have undergone (partial) nephrectomy.


Output: Is overweight associated with improved cancer-specific survival in patients with organ-confined renal cell carcinoma?