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: Targeting the energy storing white adipose tissue (WAT) by pharmacological and dietary means in order to promote its conversion to energy expending "brite" cell type holds promise as an anti-obesity approach. Present study was designed to investigate/revisit the effect of capsaicin on adipogenic differentiation with special reference to induction of "brite" phenotype during differentiation of 3T3-L1 preadipocytes.', 'Multiple techniques such as Ca2+ influx assay, Oil Red-O staining, nutrigenomic analysis in preadipocytes and matured adipocytes have been employed to understand the effect of capsaicin at different doses. In addition to in-vitro experiments, in-vivo studies were carried out in high-fat diet (HFD) fed rats treated with resiniferatoxin (RTX) (a TRPV1 agonist) and in mice administered capsaicin.', 'TRPV1 channels are expressed in preadipocytes but not in adipocytes. In preadipocytes, both capsaicin and RTX stimulate Ca2+ influx in dose-dependent manner. This stimulation may be prevented by capsazepine, a TRPV1 antagonist. At lower doses, capsaicin inhibits lipid accumulation and stimulates TRPV1 gene expression, while at higher doses it enhances accumulation of lipids and suppresses expression of its receptor. In doses of 0.1-100 µM, capsaicin promotes expression of major pro-adipogenic factor PPARγ and some of its downstream targets. In concentrations of 1 µM, capsaicin up-regulates anti-adipogenic genes. Low-dose capsaicin treatment of 3T3-L1 preadipocytes differentiating into adipocytes results in increased expression of brown fat cell marker genes. In white adipose of mice, capsaicin administration leads to increase in browning-specific genes. Global TRPV1 ablation (i.p. by RTX administration) leads to increase in locomotor activity with no change in body weight.\Question: Does capsaicin induce `` brite '' phenotype in differentiating 3T3-L1 preadipocytes?

SOLUTION: Our findings suggest the dual modulatory role of capsaicin in adipogenesis. Capsaicin inhibits adipogenesis in 3T3-L1 via TRPV1 activation and induces brown-like phenotype whereas higher doses.

PROBLEM: Context: Prognosis and treatment of patients with breast carcinoma of no special type (NST) is dependent on a few established parameters, such as tumor size, histological grade, lymph node stage, expression of estrogen receptor, progesterone receptor, and HER-2/neu, and proliferation index. The original Nottingham Prognostic Index (NPI) employs a three-tiered classification system that stratifies patients with breast cancer into good, moderate, and poor prognostic groups. The aim of our study was to use robust immunohistochemical methodology for determination of ER, PR, HER-2/neu, Ki-67, p53, and Bcl-2, and to observe differences in the expression of these markers when patients are stratified according to the original, three-tiered Nottingham Prognostic Index.', 'Paraffin blocks from 120 patients diagnosed with breast carcinoma, NST, were retrieved from our archive. Cases included in the study were female patients previously treated with modified radical mastectomy and axillary dissection.', 'Our study demonstrates that expression of markers of good prognosis, such as ER, PR, and Bcl-2, is seen with higher frequency in good and moderate NPI groups. In contrast, overexpression of HER-2/neu, a marker of adverse prognosis, is more frequent in moderate and poor NPI groups. High proliferation index, as measured by Ki-67, is seen in moderate and poor NPI groups, whereas low proliferation index is seen in good NPI groups.\Question: Does classification of patients with breast cancer according to Nottingham prognostic index highlight significant differences in immunohistochemical marker expression?

SOLUTION: These data confirm that the original, three-tiered NPI statistically correlates with the expression of prognostic immunohistochemical markers in breast carcinoma NST.

PROBLEM: Context: The use of intensity-modulated radiation therapy (IMRT) in rectal cancer has steadily increased over traditional 3D conformal radiotherapy (3D-CRT) due to perceived benefit of delivering higher treatment doses while minimizing exposure to surrounding tissues. However, IMRT is technically challenging and costly, and its effects on rectal cancer outcomes remain unclear.', 'Adults with clinical stage II and III rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy with 45-54\xa0Gy of radiation and surgery were included from the 2006-2013 National Cancer Data Base. Patients were grouped based the modality of radiation received: IMRT or 3D-CRT. Multivariable regression modeling adjusting for demographic, clinical, and treatment characteristics was used to examine the impact of IMRT vs. 3D-CRT on pathologic downstaging, resection margin positivity, sphincter loss surgery, 30-day unplanned readmission and mortality after surgery, and overall survival.', 'Among 7386 patients included, 3330 (45\xa0%) received IMRT and 4056 (55\xa0%) received 3D-CRT. While the mean radiation dose delivered was higher with IMRT (4735 vs. 4608\xa0cGy, p\u2009<\u20090.001), it was associated with higher risks of positive margins (adjusted odds ratio (OR) 1.57; p\u2009<\u20090.001) and sphincter loss surgery (OR 1.32; p\u2009<\u20090.001). There were no differences between IMRT and 3D-CRT in the likelihood of pathologic downstaging (OR 0.89, p\u2009=\u20090.051), unplanned readmission (OR 0.79; p\u2009=\u20090.07), or 30-day mortality (OR 0.61; p\u2009=\u20090.31) after surgery. Additionally, there were no differences in overall survival at 8\xa0years (IMRT vs. 3D-CRT: 64 vs. 64\xa0%; adjusted hazard ratio 1.06, p\u2009=\u20090.47).\Question: Is intensity-Modulated Radiation Therapy Associated with Perioperative or Survival Benefit over 3D-Conformal Radiotherapy for Rectal Cancer?

SOLUTION:
IMRT is associated with worse local tumor control without any long-term survival benefit for patients with locally advanced rectal cancer. Given the lack of significant advantage and the higher cost of IMRT, caution should be exercised when using IMRT instead of traditional 3D-CRT for rectal cancer.