TASK DEFINITION: Given a passage, 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.
PROBLEM: Cancer cells frequently exhibit resistance to the cytotoxic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Pretreatment of TRAIL-resistant cells with cisplatin sensitizes them to this ligand. Cisplatin also has been shown to enhance adenoviral transgene expression.', 'This study aims to evaluate the ability of cisplatin to enhance the expression and the cytotoxic effect of the tumor-specific adenoviral vector Ad/gTRAIL, which expresses a green fluorescent protein-TRAIL fusion protein.', 'Cultured cancer cells and normal human cells were infected with Ad/gTRAIL with or without cisplatin pretreatment. Adenoviral transgene expression was determined by using flow cytometry to measure green fluorescent protein fluorescence. Cytotoxicity was measured by using thiazolyl blue tetrazolium bromide assays and an apoptosis enzyme-linked immunosorbent assay kit.', 'Green fluorescent protein-TRAIL fusion protein expression was significantly enhanced by cisplatin pretreatment in cancer cells. Cisplatin treatment before Ad/gTRAIL infection resulted in a 2- to 12-fold increase in green fluorescent protein fluorescence intensity across cancer lines. Although Ad/gTRAIL induced mild cytotoxicity in all cancer lines (inhibitory concentration of 50% values of >500 pfu/cell), pretreatment with cisplatin resulted in a dose-dependent enhancement of Ad/gTRAIL-mediated cytotoxicity, as indicated by the drastic reduction of inhibitory concentration of 50% values to 4 to 42 pfu/cell in all cell lines. There was no cytotoxicity noted in normal cells treated with both cisplatin and Ad/gTRAIL.

SOLUTION: Does cisplatin enhance apoptosis induced by a tumor-selective adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand?

PROBLEM: Successful treatment of oesophageal cancer is hampered by recurrent drug resistant disease. We have previously demonstrated the importance of apoptosis and autophagy for the recovery of oesophageal cancer cells following drug treatment. When apoptosis (with autophagy) is induced, these cells are chemosensitive and will not recover following chemotherapy treatment. In contrast, when cancer cells exhibit only autophagy and limited Type II cell death, they are chemoresistant and recover following drug withdrawal.', 'MicroRNA (miRNA) expression profiling of an oesophageal cancer cell line panel was used to identify miRNAs that were important in the regulation of apoptosis and autophagy. The effects of miRNA overexpression on cell death mechanisms and recovery were assessed in the chemoresistant (autophagy inducing) KYSE450 oesophageal cancer cells.', 'MiR-193b was the most differentially expressed miRNA between the chemosensitive and chemoresistant cell lines with higher expression in chemosensitive apoptosis inducing cell lines. Colony formation assays showed that overexpression of miR-193b significantly impedes the ability of KYSE450 cells to recover following 5-fluorouracil (5-FU) treatment. The critical mRNA targets of miR-193b are unknown but target prediction and siRNA data analysis suggest that it may mediate some of its effects through stathmin 1 regulation. Apoptosis was not involved in the enhanced cytotoxicity. Overexpression of miR-193b in these cells induced autophagic flux and non-apoptotic cell death.

SOLUTION: Does miR-193b promote autophagy and non-apoptotic cell death in oesophageal cancer cells?

PROBLEM: Ascent to high altitude leads to a reduction in ambient pressure and a subsequent fall in available oxygen. The resulting hypoxia can lead to elevated pulmonary artery (PA) pressure, capillary stress, and an increase in interstitial fluid. This fluid can be assessed on lung ultrasound (LUS) by the presence of B-lines. We undertook a chamber and field study to assess the impact of high-intensity exercise in hypoxia on the development of pulmonary interstitial edema in healthy lowlanders.', 'Thirteen volunteers completed a high-intensity intermittent exercise (HIIE) test at sea level, in acute normobaric hypoxia (12% O2, approximately 4090 m equivalent altitude), and in hypobaric hypoxia during a field study at 4090 m after 6 days of acclimatization. Pulmonary interstitial edema was assessed by the evaluation of LUS B-lines.', 'After HIIE, no increase in B-lines was seen in normoxia, and a small increase was seen in acute normobaric hypoxia (2 ± 2; P < .05). During the field study at 4090 m, 12 participants (92%) demonstrated 7 ± 4 B-lines at rest, which increased to 17 ± 5 immediately after the exercise test (P < .001). An increase was evident in all participants. There was a reciprocal fall in peripheral arterial oxygen saturations (Spo2) after exercise from 88% ± 4% to 80% ± 8% (P < .01). B-lines and Spo2 in all participants returned to baseline levels within 4 hours.

SOLUTION:
Does high-intensity intermittent exercise increase pulmonary interstitial edema at altitude but not at simulated altitude?