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.

Ex Input:
Context: Patients affected by chronic lymphocytic leukemia (CLL) have an increased risk of developing a second cancer. There is not a definitive explanation for this phenomenon, although some hypotheses have been postulated. The aim of the present work was to assess the presence of second cancer in untreated patients with CLL who were cytogenetically characterized, and secondly to investigate if there is a correlation between the genetics of CLL and the emergence of second cancer.', 'We performed conventional cytogenetics and Fluorescent in situ hybridization analyses in a series of 106 patients.', 'We observed that nearly 8% of cases developed second cancer, mostly epithelial tumors. The majority of them presented two common features, del(13)(q14.3) and the presence of at least two genetic alterations.
Answer: We suggest that the genetic background of CLL, particularly the presence of several genetic alterations, influences the emergence of second cancer in patients affected by CLL.

Ex Output:
Does genetics of lymphocytes influence the emergence of second cancer in chronic lymphocytic leukemia?

Ex Input:
Context: To simultaneously study the effect of a selective cyclooxygenase-2 (COX-2) inhibitor and that of a classic non-steroidal anti-inflammatory drug (NSAID) on the expression of pro-inflammatory genes in the cartilage of patients with severe knee osteoarthritis (OA) and in cultured human OA chondrocytes.', 'A 3-month clinical trial was carried out on 30 patients with severe knee OA scheduled for knee replacement surgery. Patients were randomized into two groups: patients treated with celecoxib (CBX) and patients treated with aceclofenac (ACF). OA patients who did not want to be treated served as the control group. After surgery, cartilage was processed for molecular biology studies. We also employed cultured chondrocytes from different OA patients to examine NSAID effects on pro-inflammatory gene expression in cells stimulated with interleukin (IL)-1beta.', 'Both CBX and ACF inhibited COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and inducible nitric oxide synthase (iNOS) synthesis in the articular cartilage of OA patients. In cultured chondrocytes, both NSAID decreased COX-2 and mPGES-1 synthesis and prostaglandin E2 (PGE2) release induced by IL-1beta, while no effect was observed on nitric oxide or iNOS synthesis. In OA patients, only CBX decreased tumor necrosis factor alpha and IL-1beta expression in the cartilage, while both NSAID diminished IL-1beta induced cytokine synthesis in cultured OA chondrocytes.
Answer: Both NSAID diminished PGE2 release and induced a decrease in COX-2 and mPGES-1 synthesis in the cartilage from OA patients and in OA chondrocytes. These data suggest that prolonged therapy with PGE2 blocking agents decreases PGE2 production not only by direct inhibition of COX-2 activity, but also by down-regulating COX-2 and mPGES-1 synthesis in the cartilage. However, CBX and ACF seem to have a different anti-inflammatory profile in controlling pro-inflammatory gene expression in the cartilage.

Ex Output:
Does long-term NSAID treatment directly decrease COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis?

Ex Input:
Context: Matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9) play a key role in tissue remodelling after processes such as joint destruction in rheumatoid arthritis. Their expression may reflect the disease activity and they could therefore represent a useful marker to assess the efficacy of therapy. In this study MMP-2 and MMP-9 serum were evaluated in patients with chronic arthritis during therapy with the anti-TNFalpha mAb, infliximab.', 'Fifty patients with chronic arthritis, 26 with rheumatoid arthritis and 24 with undifferentiated chronic arthritis, were recruited and treated with infliximab (3 mg/kg). Serum concentrations of MMP-2 and MMP-9 were serially measured by gelatine zymography at baseline and after two and fourteen weeks of infliximab therapy. DAS-28 and ACR response criteria were applied to assess disease activity and clinical improvement. Twenty-four healthy donors were included in the study as controls.', 'Although therapy with infliximab induced a statistically significant reduction of the DAS-28 score and improvement of the ACR clinical response, MMP-2 and MMP-9 serum concentrations were not modulated during therapy with infliximab.
Answer: Our study provides further evidence that blocking TNFalpha by infliximab is a powerful tool in the management of chronic arthritis. Nevertheless, infliximab does not seem to be able to modify the serum expression of MMP-2 and MMP-9, probably because modification of these enzymes is restricted to the site of joint inflammation and serum detection can not truly mirror the local situation. Additional soluble factors correlating with joint damage should be investigated as possible markers for monitoring anti-TNFalpha therapy.

Ex Output:
Does infliximab therapy modify MMP-2 and MMP-9 serum concentrations in chronic arthritis?