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.

[Q]: Context: Doxorubicin is a cytotoxic drug with potential for severe myelosuppression that is highly variable and poorly predictable.', 'We correlated CBR1 and CBR3 genotypes with the pharmacokinetics and pharmacodynamics of doxorubicin in 101 Southeast Asian breast cancer patients receiving first-line doxorubicin.', 'A common CBR3 11G>A variant was associated with lower doxorubicinol area under the concentration-time curve (AUC)/doxorubicin AUC metabolite ratio (P=0.009, GG vs. AA; trend test, P=0.004), lower CBR3 expression in breast tumor tissue (P=0.001, GG vs. AA), greater tumor reduction (P=0.015, GG vs. AA), and greater percentage reduction of leukocyte and platelet counts at nadir (trend test, P < or = 0.03). Chinese and Malays had higher frequency of the CBR3 11G>A variant than Indians (P < or = 0.002). Another variant CBR3 730G>A was associated with higher doxorubicinol AUC (P=0.009, GG vs. AA) and CBR3 expression in breast tumor tissue (P=0.001, GG vs AA).
Answer: Polymorphisms in CBR3 may explain interindividual and interethnic variability of doxorubicin pharmacokinetics and pharmacodynamics.
[A]: Does genotype of human carbonyl reductase CBR3 correlate with doxorubicin disposition and toxicity?


[Q]: Context: Endoplasmic reticulum (ER) stress is induced in many forms of chronic liver disease and may promote the development of hepatocellular carcinoma. The activator protein 1 (AP-1) complex is a transcription factor that promotes hepatic carcinogenesis in response to cellular stress. The aim of this study was to determine the role of ER stress in the regulation of the hepatic AP-1 complex.', 'Human hepatocellular carcinoma (HepG2) cells and C57BL/6J mice were subjected to pharmacologic ER stress and the expression of AP-1-associated genes and proteins was assessed. To determine the role of MAPK signaling in ER stress-induced AP-1 activation, ER stress was induced in JNK- and ERK-inhibited HepG2 cells.', 'Induction of ER stress promoted the activation of both Jun- and Fos-related genes and proteins of the AP-1 complex in HepG2 cells and murine liver. Inhibition of ERK phosphorylation in HepG2 cells completely prevented ER stress-induced activation of the fos-related components of AP-1 whereas activation of Jun-related components was only partially attenuated. Conversely, inhibition of JNK phosphorylation in HepG2 cells reduced ER stress-induced activation of Jun-related components but did not prevent activation of fos-related components.
Answer: ER stress activates the hepatic AP-1 complex via MAPK-dependent signaling pathways. ER stress-induced activation of Fos-related components is dependent primarily on ERK activation whereas ER stress-induced activation of Jun-related components is dependent primarily on JNK activation, although there is interplay between these regulatory pathways. These data implicate a novel signaling pathway by which sustained ER stress, as observed in many chronic liver diseases, may promote hepatic carcinogenesis.
[A]: Does endoplasmic reticulum stress activate the hepatic activator protein 1 complex via mitogen activated protein kinase-dependent signaling pathways?


[Q]: Context: Studies on the safety of aprotinin in coronary artery surgery have given conflicting results. Therefore, we studied the possible link between perioperative aprotinin treatment and renal dysfunction in patients undergoing first-time coronary surgery with a high risk of bleeding.', 'We performed a matched cohort study, comparing 200 patients receiving high-dose aprotinin with 200 patients receiving tranexamic acid during primary isolated coronary surgery. Patients were matched according to age, sex, and presence of acute coronary syndrome. Primary outcome was fractional change in creatinine clearance. Secondary outcomes were other evaluations of postoperative renal function, mortality, stroke, reoperation for bleeding, and transfusion requirements.', 'The groups were similar in baseline characteristics except that triple-vessel disease and history of myocardial infarction were more prevalent in the aprotinin group. No significant differences were found in fractional change in creatinine clearance (-11% versus -12%, medians, p = 0.75) or any other assessments of postoperative renal function between the tranexamic acid and the aprotinin group. Adverse event rates were similar: early mortality (3.5% versus 4.5%, p = 0.80), stroke (1.5% versus 2%, p = 1.0), reoperation for bleeding (3.5% versus 2.5%, p = 0.77), and 5-year survival (87% versus 84%, p = 0.17). Patients in the aprotinin group received fewer transfusions (48% versus 60.5%, p = 0.02), fewer units of packed red blood cells (2.0 versus 1.4, p = 0.02) and plasma (1.3 versus 0.5, p < 0.001), but more units of platelets (0.1 versus 0.2, p = 0.02).
Answer: Aprotinin treatment during primary coronary surgery was not associated with impaired postoperative renal function in comparison with patients treated with tranexamic acid.
[A]:
Is aprotinin associated with postoperative renal impairment after primary coronary surgery?