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.
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Question: AVE9633 is a new immunoconjugate comprising a humanized monoclonal antibody, anti-CD33 antigen, linked through a disulfide bond to the maytansine derivative DM4, a cytotoxic agent and potent tubulin inhibitor. It is undergoing a phase I clinical trial. Chemoresistance to anti-mitotic agents has been shown to be related, in part, to overexpression of ABC proteins. The aim of the present study was to investigate the potential roles of P-gp, MRP1 and BCRP in cytotoxicity in AVE9633-induced acute myeloid leukaemia (AML).', 'This study used AML cell lines expressing different levels of P-gp, MRP1 or BCRP proteins and twenty-five samples from AML patients. Expression and functionality of the transporter protein were analyzed by flow cytometry. The cytotoxicity of the drug was evaluated by MTT and apoptosis assays.', 'P-gp activity, but not MRP1 and BCRP, attenuated AVE9633 and DM4 cytotoxicity in myeloid cell lines. Zosuquidar, a potent specific P-gp inhibitor, restored the sensitivity of cells expressing P-gp to both AVE9633 and DM4. However, the data from AML patients show that 10/25 samples of AML cells (40%) were resistant to AVE9633 or DM4 (IC(50) > 500 nM), and this was not related to P-gp activity (p-Value: 0.7). Zosuquidar also failed to re-establish drug sensitivity. Furthermore, this resistance was not correlated with CD33 expression (p-Value: 0.6) in those cells.

Answer: Is p-gp activity a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines , but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients?


Question: The objective of this study is to characterize differential proteomic expression among well-differentiation and poor-differentiation colorectal carcinoma tissues and normal mucous epithelium.', 'The study is based on quantitative 2-dimensional gel electrophoresis and analyzed by PDquest.', 'Excluding redundancies due to proteolysis and posttranslational modified isoforms of over 600 protein spots, 11 proteins were revealed as regulated with statistical variance being within the 95th confidence level and were identified by peptide mass fingerprinting in matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Progression-associated proteins belong to the functional complexes of tumorigenesis, proliferation, differentiation, metabolism, and the regulation of major histocompatibility complex processing and other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in CRC. Among various differentiation stage of CRC tissues, we identified calreticulin precursor, MHC class I antigen (human leukocyte antigen A ), glutathione S-transferase pi1, keratin 8, heat shock protein 27, tubulin beta chain, triosephosphate, fatty acid-binding protein, hemoglobin (deoxy) mutant with val b 1 replaced by met (HBB), and zinc finger protein 312 (FEZF2).

Answer: Does proteomic analysis reveal novel proteins associated with progression and differentiation of colorectal carcinoma?


Question: To test our hypothesis that lower intakes of previously identified cardioprotective nutrients would be associated with the coronary epidemic in Central and Eastern Europe.', 'We conducted a survey of coronary mortality in 16 countries and diet in 19 countries.', 'Countries were placed in four groups with different cultural patterns (Central and Eastern Europe, including Russia; Western Europe and the United States; Mediterranean; and Asian).', 'Independent predictors of coronary mortality.', 'Means and standard deviations were calculated, and analysis of variance with Bonferroni post hoc tests and backward elimination regression analysis was conducted.', 'Coronary mortality was highest in Central and Eastern Europe followed by Western Europe and the United States, the Mediterranean countries, and Asia (Japan). The model with folate, fiber, and n-6/n-3 fatty acids explained the majority of variation in coronary mortality (men 86%, women 90%). Most of the variation was explained by folate (men 61%, women 62%). The picture is complicated by the fact that folate, lutein/zeaxanthin, and beta-carotene were highly intercorrelated ( r =0.87 to 0.99).

Answer:
Are diets lower in folic acid and carotenoids associated with the coronary disease epidemic in Central and Eastern Europe?