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.

Ex Input:
Context: Resistance to cisplatin-centered chemotherapy is a major cause of treatment failure in human ovarian cancer. Whereas PTEN, a tumor suppressor gene product, is believed to promote apoptosis primarily via inactivation of the PI3K/Akt cell survival pathway, recent evidence suggests that PTEN may function independently of this pathway. Activation of p53 is a key determinant of sensitivity to cisplatin-induced apoptosis. Whether PTEN can facilitate cisplatin sensitivity, and this involves the activation of p53, remains unclear. In this study, we determined whether and how PTEN over-expression sensitizes ovarian cancer cells to CDDP-induced apoptosis.', 'Using pairs of chemosensitive and chemoresistant ovarian cancer cell lines (OV20028 vs. C13* and A2780-s vs. A2780-cp) as an in vitro model, we have examined the influence of PTEN over-expression in regulation of cisplatin-induced apoptosis. Apoptosis was assessed morphologically by Hoechst staining and confirmed by the detection of cleaved products of caspase-3 and PARP by Western blot. Over-expression of PTEN by PTEN cDNA transfection up-regulates p53 content and increases the sensitivity of chemoresistant cells to cisplatin-induced apoptosis without detectable changes in the levels of phosphorylated Akt and FKHR as well as FasL mRNA abundance as determined by Western blot and RT-PCR, respectively. PTEN-mediated chemosensitization was attenuated by p53 down-regulation by siRNA in C13*, a chemoresistant wild-type p53 cell. Moreover, PTEN over-expression failed to sensitize the chemoresistant p53 mutant ovarian cancer cell line A2780-cp to cisplatin-induced apoptosis, unless wild-type p53 was reconstituted by adenoviral p53 infection.
Answer: Taken together, these data suggest that PTEN over-expression may represent a novel therapeutic approach for chemoresistant human ovarian cancer and that this may involve a p53-mediated apoptotic cascade independent of the PI3K/Akt pathway.

Ex Output:
Does over-expression of PTEN sensitize human ovarian cancer cells to cisplatin-induced apoptosis in a p53-dependent manner?

Ex Input:
Context: Severe mitral regurgitation (MR) reduces left atrial thrombus formation in patients with mitral stenosis (MS) and atrial fibrillation (AF). Plasma D-dimer levels represent a biochemical marker for fibrinolytic activity in prothrombotic states. The prothrombotic burden in patients with mitral valve disease and/or AF was assessed using plasma D-dimer levels.', 'The study population included 89 patients with mitral valve disease, 21 with AF but normal valves, and 15 healthy controls. The mitral valve group was subdivided into patients with MS (n = 27), severe MR (n = 26), and MS with concomitant with severe MR (MS/MR; n = 36). These subgroups were further subdivided according to the atrial rhythm (sinus rhythm (SR)+AF).', 'The mean left atrial size was increased in all groups with cardiac disease. D-dimer levels were highest in the MS+AF subgroup (527 +/- 134 microg/l). Patients with MS+AF, MS+SR, and nonvalvular AF had significantly higher D-dimer levels than controls (p < 0.01, by ANOVA). Patients with MR had normal levels of D-dimer. The atrial rhythm did not influence D-dimer levels in the MS/MR subgroup, or in the pure MR subgroup (p = NS).
Answer: Plasma D-dimer levels correlated with the embolic risk in mitral valve disease and non-valvular AF. The highest levels were found in patients with MS+AF and non-valvular AF. Severe MR decreased the D-dimer levels in MS and/or AF to control levels.

Ex Output:
Does mitral regurgitation reduce systemic coagulation activity in patients with rheumatic heart disease?

Ex Input:
Context: Sub-lethal doses of ionizing radiation (IR) can alter the phenotype of target tissue by modulating genes that influence effector T cell activity. Previous studies indicate that cancer cells respond to radiation by up-regulating surface expression of death receptors, cell adhesion molecules and tumor-associated antigens (TAA). However, there is limited information available regarding how T cells themselves are altered following these interactions with irradiated tumor cells.', 'Here, several human colorectal tumor cell lines were exposed to radiation (0-10Gy) in vitro and changes in the expression of molecules costimulatory to effector T cells (4-1BBL, OX-40L, CD70, ICOSL) were examined by flow cytometry. T cell effector function was assessed to determine if changes in these proteins were directly related to the changes in T cell function.', 'We found OX-40L and 4-1BBL to be the most consistently upregulated proteins on the surface of colorectal tumor cells post-IR while ICOSL and CD70 remained largely unaltered. Expression of these gene products correlated with enhanced killing of irradiated human colorectal tumor cells by TAA-specific T-cells. Importantly, blocking of both OX-40L and 4-1BBL reversed radiation-enhanced T-cell killing of human tumor targets as well as T-cell survival and activation.
Answer: Overall, results of this study suggest that, beyond simply rendering tumor cells more sensitive to immune attack, radiation can be used to specifically modulate expression of genes that directly stimulate effector T cell activity.

Ex Output:
Is effector function of CTLs increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade?