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.

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.
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?

Chronic opioid therapy for chronic pain treatment has increased. Hospital physicians, including hospitalists and medical/surgical resident physicians, care for many hospitalized patients, yet little is known about opioid prescribing at hospital discharge and future chronic opioid use.', "We aimed to characterize opioid prescribing at hospital discharge among 'opioid naïve' patients. Opioid naïve patients had not filled an opioid prescription at an affiliated pharmacy 1 year preceding their hospital discharge. We also set out to quantify the risk of chronic opioid use and opioid refills 1 year post discharge among opioid naïve patients with and without opioid receipt at discharge.", 'This was a retrospective cohort study.', 'From 1 January 2011 to 31 December 2011, 6,689 opioid naïve patients were discharged from a safety-net hospital.', 'Chronic opioid use 1 year post discharge.', 'Twenty-five percent of opioid naïve patients (n\u2009=\u20091,688) had opioid receipt within 72 hours of discharge. Patients with opioid receipt were more likely to have diagnoses including neoplasm (6.3% versus 3.5%, p\u2009<\u20090.001), acute pain (2.7% versus 1.0 %, p\u2009<\u20090.001), chronic pain at admission (12.1% versus 3.3%, p\u2009<\u20090.001) or surgery during their hospitalization (65.1% versus 18.4%, p\u2009<\u20090.001) compared to patients without opioid receipt. Patients with opioid receipt were less likely to have alcohol use disorders (15.7% versus 20.7%, p\u2009<\u20090.001) and mental health disorders (23.9% versus 31.4%, p\u2009<\u20090.001) compared to patients without opioid receipt. Chronic opioid use 1 year post discharge was more common among patients with opioid receipt (4.1% versus 1.3%, p\u2009<\u20090.0001) compared to patients without opioid receipt. Opioid receipt was associated with increased odds of chronic opioid use (AOR\u2009=\u20094.90, 95% CI 3.22-7.45) and greater subsequent opioid refills (AOR\u2009=\u20092.67, 95% CI 2.29-3.13) 1 year post discharge compared to no opioid receipt.
Does opioid Prescribing at Hospital Discharge contribute to Chronic Opioid Use?

To measure the clearance intraperitoneal mitomycin C and doxorubicin in patients having peritonectomy and analyze the impact of the extent of peritoneal resection on pharmacokinetics.', 'A group of 15 patients with peritoneal carcinomatosis were submitted to cytoreductive surgery and heated intraperitoneal chemotherapy. Ten patients received mitomycin C and five, doxorubicin. Six patients underwent total parietal peritonectomy and nine had less-extensive peritonectomy. Pharmacokinetics were determined by sampling peritoneal fluid and blood. Drug concentrations over time, area under the curve ratios and the amount of drug recovered from the peritoneal cavity were calculated and compared between the groups.', 'The concentrations of mitomycin C over time in the peritoneal fluid and plasma were similar in five patients with total parietal peritonectomy as compared to five patients with less-extensive peritonectomy ( P=0.5350 and 0.6991; Mann-Whitney test). Mitomycin C area under the curve ratio in total peritonectomy patients was 20.5 and 25.7 in patients with less-extensive peritonectomy. The difference in total amount of drug recovered from the peritoneal cavity was not significant (30.6+/-6.188% versus 22.6+/-3.84%, P=0.095). In the studies with doxorubicin, one patient underwent total parietal peritonectomy with similar pharmacokinetics to four patients submitted to partial peritonectomy.

Does extent of parietal peritonectomy change intraperitoneal chemotherapy pharmacokinetics?