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: 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).

SOLUTION: Does genotype of human carbonyl reductase CBR3 correlate with doxorubicin disposition and toxicity?

PROBLEM: Cervical carcinoma is the second most common malignancy in females and most of the cases are found in developing countries. The objectives of the present study were (a): to demonstrate the antiproliferative and apoptotic effects of Achillea falcata (A.falcata) extract in human cervical cancer cells (HeLa), and (b): to study the effect of the extract on cellular morphology, cell cycle phase distribution and mitochondrial membrane potential.', 'MTT assay was used to evaluate the anticancer effect of the extract on HeLa cells. Phase contrast, fluorescence microscopy and transmission electron microscopy (TEM) were used to investigate the morphological changes in these cancer cells after extract treatment. Flow cytometry was used to evaluate the effects of the extract on cell cycle and mitochondrial membrane potential.', 'The results revealed that A. falcata extract led to a significant antiproliferative effect in HeLa cancer cells. The extract induced cellular shrinkage, chromatin condensation and appearance of apoptotic bodies which are the hallmarks of cellular apoptosis. TEM results showed that extract-treated cells had nuclear membrane which was hemispherical and the nuclear chromatin was concentrated and bundled on the inner border of karyotheca. The endoplasmic reticulum also became enlarged in the inner segment. The extract also induced G2/M phase cell cycle arrest along with loss of mitochondrial membrane potential.

SOLUTION: Are antiproliferative and apoptotic effects of the ethanolic herbal extract of Achillea falcata in human cervical cancer cells mediated via cell cycle arrest and mitochondrial membrane potential loss?

PROBLEM: Cardiovascular magnetic resonance T1 mapping characteristics are elevated in adult cancer survivors; however, it remains unknown whether these elevations are related to age or presence of coincident cardiovascular comorbidities.', 'We performed blinded cardiovascular magnetic resonance analyses of left ventricular T1 and extracellular volume (ECV) fraction in 327 individuals (65% women, aged 64±12 years). Thirty-seven individuals had breast cancer or a hematologic malignancy but had not yet initiated their treatment, and 54 cancer survivors who received either anthracycline-based (n=37) or nonanthracycline-based (n=17) chemotherapy 2.8±1.3 years earlier were compared with 236 cancer-free participants. Multivariable analyses were performed to determine the association between T1/ECV measures and variables associated with myocardial fibrosis. Age-adjusted native T1 was elevated pre- (1058±7 ms) and post- (1040±7 ms) receipt of anthracycline chemotherapy versus comparators (965±3 ms; P<0.0001 for both). Age-adjusted ECV, a marker of myocardial fibrosis, was elevated in anthracycline-treated cancer participants (30.4±0.7%) compared with either pretreatment cancer (27.8±0.7%; P<0.01) or cancer-free comparators (26.9±0.2%; P<0.0001). T1 and ECV of nonanthracycline survivors were no different than pretreatment survivors (P=0.17 and P=0.16, respectively). Native T1 and ECV remained elevated in cancer survivors after accounting for demographics (including age), myocardial fibrosis risk factors, and left ventricular ejection fraction or myocardial mass index (P<0.0001 for all).

SOLUTION:
Do anthracycline-Associated T1 Mapping Characteristics Are Elevated Independent of the Presence of Cardiovascular Comorbidities in Cancer Survivors?