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: 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.\Question: Does genetics of lymphocytes influence the emergence of second cancer in chronic lymphocytic leukemia?

SOLUTION: 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.

PROBLEM: Context: 5-year survival for melanoma metastasis to regional lymph nodes (American Joint Committee on Cancer stage III) is <50%. Knowledge of outcomes following therapeutic lymphadenectomy for stage III melanoma related to BRAF status may guide adjuvant use of BRAF/MEK inhibitors along with established and future therapies.', 'To determine patterns of melanoma recurrence and survival following therapeutic lymph node dissection (TLND) associated with oncogenic mutations.', 'DNA was obtained from patients who underwent TLND and had 2 positive nodes, largest node >3cm or extracapsular invasion. Mutations were detected using an extended Sequenom MelaCARTA panel.', 'Mutations were most commonly detected in BRAF (57/124 [46%] patients) and NRAS (26/124 [21%] patients). Patients with BRAF mutations had higher 3-year recurrence rate (77%) versus 54% for BRAF wild-type patients (hazard ratio (HR) 1.8, p=0.008). The only prognostically significant mutations occurred in BRAF: median recurrence-free (RFS) and disease-specific survival (DSS) for BRAF mutation patients was 7 months and 16 months, versus 19 months and not reached for BRAF wild-type patients, respectively. Multivariate analysis identified BRAF mutant status and number of positive lymph nodes as the only independent prognostic factors for RFS and DSS.\Question: Is bRAF mutation status an independent prognostic factor for resected stage IIIB and IIIC melanoma : implications for melanoma staging and adjuvant therapy?

SOLUTION: Patients with BRAF mutations experienced rapid progression of metastatic disease with locoregional recurrence rarely seen in isolation, supporting incorporation of BRAF status into melanoma staging and use of BRAF/MEK inhibitors post-TLND.

PROBLEM: Context: We compare the effects of postinjury administration of allopregnanolone, a metabolite of progesterone, to progesterone in an animal model of transient middle cerebral artery occlusion.', 'Focal cerebral ischemia was induced in age-matched, adult, male, Sprague-Dawley rats by using an intraluminal filament and suture method to occlude the right middle cerebral artery. After 120 minutes of middle cerebral artery occlusion, the occluding filament was withdrawn to allow reperfusion. Laser-Doppler flowmetry was used to monitor cerebral blood flow for the entire 2-hour period of occlusion and for 5 minutes after reperfusion. Animals subjected to middle cerebral artery occlusion received injections of allopregnanolone (8 mg/kg, n=6), progesterone (8 mg/kg, n=6) and vehicle (2-hydroxypropyl-beta-cyclodextrin, n=7) at 2 hours (intraperitoneally 5 minutes before reperfusion) and 6 hours (subcutaneously) postocclusion. Brains were removed at 72 hours post-middle cerebral artery occlusion, sectioned into coronal slices, and stained with 2,3,5-triphenyltetrazolium chloride (TTC). In a blinded analysis, infarct volume was calculated by using computer-aided morphometry to measure brain areas not stained with TTC.', 'After progesterone or allopregnanolone treatment, stained sections revealed a significant reduction in cortical, caudate-putamen, and hemispheric infarct volumes (percentage of contralateral structure) compared with vehicle-injected controls. Cortical infarction (percentage of contralateral cortex) was 37.47%+/-10.57% (vehicle), 25.49%+/-7.38% (progesterone; P<.05 from vehicle), and 11.40%+/-7.09% (allopregnanolone; P<.05 from vehicle; P<.05 from progesterone). Caudate-putamen infarction (percentage of contralateral caudate-putamen) was 78.02%+/-22.81% (vehicle), 48.41%+/-22.44% (progesterone; P<.05 from vehicle), and 50.44%+/-10.90% (allopregnanolone; P<.05 from vehicle). Total hemispheric infarction (percentage of contralateral hemisphere) was 24.37%+/-6.69% (vehicle), 15.95%+/-3.59% (progesterone; P<.05 from vehicle), and 11.54%+/-3.71% (allopregnanolone; P<.05 from vehicle). No significant differences in cerebral blood flow between groups and time points during ischemia and early reperfusion were observed, suggesting that the relative ischemic insult was equivalent among all groups.\Question: Is allopregnanolone , a progesterone metabolite , more effective than progesterone in reducing cortical infarct volume after transient middle cerebral artery occlusion?

SOLUTION:
Although progesterone and allopregnanolone are effective in reducing infarct pathology, allopregnanolone is more potent than progesterone in attenuating cortical damage. Our results suggest that both neurosteroids should be examined for safety and efficacy in a clinical trial for ischemic stroke.