TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: To investigate the role of S100A3 and the effect of S100A3 inhibition on human castration-resistant prostate cancer (CRPC) cells by using in vitro and in vivo functional assays.', 'Using human CRPC cells (PC3 and DU145), S100A3 expression levels were assessed by reverse transcription-polymerase chain reaction and Western blot analysis. After S100A3-specific small interfering ribonucleic acid (RNA) treatment, cell viability was determined by Cell Counting Kit-8 assay, and apoptotic cell fractions were evaluated by flow cytometry. The invasive properties of these cells and the expression pattern of matrix metalloproteinases (MMPs) were assessed using transwell migration assays, reverse transcription-polymerase chain reaction, and gelatin zymography. Finally, the in vivo efficacy of S100A3 inhibition on human CRPC cells was investigated using human tumor xenograft models in nude mice.', 'Human CRPC cells showed overexpression of S100A3, and its suppression reduced cell viability owing to apoptotic cell death. Additionally, S100A3 inhibition decreased the invasiveness of human CRPC cells. Moreover, MMP-2 and MMP-9 were downregulated in PC3, whereas only MMP-9 was downregulated in D145 after S100A3 inhibition. In human CRPC xenograft models, we noted a marked reduction in tumor growth in mice injected with S100A3 short hairpin RNA-transfected PC3 and DU145 cells.\Question: Does s100A3 suppression inhibit in vitro and in vivo tumor growth and invasion of human castration-resistant prostate cancer cells?

SOLUTION: Human CRPC cells showed upregulation of S100A3 expression, and S100A3 inhibition reduced tumor cell viability. S100A3 inhibition reduced invasion capability with downregulation of MMP expression. More importantly, S100A3 inhibition resulted in tumor growth suppression in human CRPC xenograft models, suggesting S100A3 could serve as a novel therapeutic target for the treatment of human CRPC.

PROBLEM: Context: The PlA1/A2 polymorphism of platelet glycoprotein IIIa (GPIIIa) has been implicated in the pathogenesis of type 2 diabetes. We studied this polymorphism in a homogenous, extensively phenotyped cohort using the candidate gene approach.', 'The PlA1/A2 polymorphism was determined in 1051 patients with type 2 diabetes and in 2247 individuals without type 2 diabetes.', 'In patients with type 2 diabetes, genotype frequencies were as follows: PlA1/A1 71.4%, PlA1/A2 26.0%, and PlA2/A2 2.7%. In individuals without type 2 diabetes, genotype frequencies were 71.6%, 25.7% and 2.8%, respectively. The PlA2 allele was not associated with fasting and postprandial glucose, glycated haemoglobin, insulin, proinsulin, C-peptide and calculated indices of insulin resistance or pancreatic beta cell function. The PlA2 allele was also not significantly associated with angiographic CHD (adjusted odds ratio [OR] 1.13; 95% CI, 0.93-1.39) or with a history of previous myocardial infarction (adjusted OR 1.09; 95% CI, 0.87-1.37).\Question: Is the PlA1/A2 polymorphism of platelet glycoprotein IIIa associated with the risk of type 2 diabetes . The Ludwigshafen Risk and Cardiovascular Health study?

SOLUTION: The GPIIIa PlA1/A2 polymorphism is not associated with type 2 diabetes, glucose metabolism, angiographic CHD or myocardial infarction.

PROBLEM: Context: Subclinical hypercortisolism (SH) is suggested to exert a deleterious effect on bone. This effect and the role of gonadal status in male subjects are not fully elucidated. We evaluated bone mineral density (BMD) and prevalence of vertebral fractures in eugonadal male subjects with adrenal incidentalomas (AI) and without SH.', 'This 12-month observational multicentre study was performed between January and December 2006 on inpatient basis in three referral Italian centres.', 'Eighty-eight consecutive eugonadal male patients with AI and 90 matched control subjects were studied.', 'All subjects underwent the determination of BMD by dual-energy X-ray absorptiometry at lumbar spine (LS) and femoral neck (FN), and spinal radiograph. In AI patients SH was diagnosed in the presence of two of the following: urinary free cortisol > 193.1 nmol/l, cortisol after 1 mg dexamethasone suppression test > 82.8 nmol/l, ACTH levels < 2.2 pmol/l.', 'As compared to patients without SH (SH-, n = 66) and controls, patients with SH (SH+, n = 22) had lower BMD at LS (Z-score: SH+, -1.04 +/- 1.84; SH-, 0.19 +/- 1.34, Controls 0.20 +/- 1.28, P = 0.001 and FN (Z-score: SH+, -0.63 +/- 1.01; SH-, 0.01 +/- 1.01, Controls 0.26 +/- 1.06, P = 0.002) and higher prevalence of fractures (SH+, 72.7%; SH-, 21.2%, Controls 20.0%, P = 0.0001). Multivariable analyses showed that SH was associated to BMD at LS (beta = -0.378, P = 0.0001) and vertebral fractures (OR = 7.81, 95% CI 1.96-31.17, P = 0.004).\Question: Do eugonadal male patients with adrenal incidentalomas and subclinical hypercortisolism have increased rate of vertebral fractures?

SOLUTION:
In eugonadal male patients with AI, SH is associated with low BMD and high prevalence of vertebral fractures.