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.

Input: Consider Input: Context: Breast cancer is a hormone-dependent cancer, and the presence of estrogen receptor alpha (ER-alpha) in tumors is used clinically to predict the likelihood of response to hormonal therapies. The clinical value of the second recently identified ER isoform, called ER-beta, is less clear, and there is currently conflicting data concerning its potential role as a prognostic or predictive factor.', 'To assess whether ER-beta expression is associated with clinical outcome, protein levels were measured by immunoblot analysis of a retrospective bank of tumor cell lysates from 305 axillary node-positive patients. A total of 119 received no adjuvant therapy, and 186 were treated with tamoxifen only. The median follow-up time was 65 months. Univariate and multivariate Cox regression modeling was done to assess the prognostic and predictive significance of ER-beta expression.', 'Expression of ER-beta protein did not correlate significantly with any other clinical variables, including ER and progesterone levels (as measured ligand binding assay), tumor size, age, or axillary nodal status. In the untreated population, those patients whose tumors who expressed both receptor isoforms exhibited the most favorable outcome as compared with those patients who had lost ER-alpha expression. However, there was no association between ER-beta levels alone and either disease-free or overall survival in the untreated patient population. In contrast, in both univariate and multivariate analyses, high levels of ER-beta predicted an improved disease-free and overall survival in patients treated with adjuvant tamoxifen therapy.\Question: Do low levels of estrogen receptor beta protein predict resistance to tamoxifen therapy in breast cancer?

Output: These findings provide evidence that ER-beta may be an independent predictor of response to tamoxifen in breast cancer. Furthermore, these results suggest that ER-beta may influence tumor progression in ways different from those mediated by the ER-alpha isoform.


Input: Consider Input: Context: Transient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel, widely expressed in neuronal cells and involved in nociception and neurogenic inflammation. We showed recently that TRPA1 mediates cartilage degradation and joint pain in the MIA-model of osteoarthritis (OA) suggesting a hitherto unknown role for TRPA1 in OA. Therefore, we aimed to investigate whether TRPA1 is expressed and functional in human OA chondrocytes.', 'Expression of TRPA1 in primary human OA chondrocytes was assessed by qRT-PCR and Western blot. The functionality of the TRPA1 channel was assessed by Ca(2+)-influx measurements. Production of MMP-1, MMP-3, MMP-13, IL-6, and PGE2 subsequent to TRPA1 activation was measured by immunoassay.', 'We show here for the first time that TRPA1 is expressed in primary human OA chondrocytes and its expression is increased following stimulation with inflammatory factors IL-1β, IL-17, LPS, and resistin. Further, the TRPA1 channel was found to be functional, as stimulation with the TRPA1 agonist AITC caused an increase in Ca(2+) influx, which was attenuated by the TRPA1 antagonist HC-030031. Genetic depletion and pharmacological inhibition of TRPA1 downregulated the production of MMP-1, MMP-3, MMP-13, IL-6, and PGE2 in osteoarthritic chondrocytes and murine cartilage, respectively.\Question: Is transient receptor potential ankyrin 1 ( TRPA1 ) functionally expressed in primary human osteoarthritic chondrocytes?

Output: The TRPA1 cation channel was found to be functionally expressed in primary human OA chondrocytes, which is an original finding. The presence and inflammatory and catabolic effects of TRPA1 in human OA chondrocytes propose a highly intriguing role for TRPA1 as a pathogenic factor and drug target in OA.


Input: Consider Input: Context: Treatment of implant-associated osteomyelitis regularly involves the use of systemic antibiotics in addition to surgical intervention. However, it remains unclear if perioperative systemic application of bactericide substances can improve overall outcome in models of severe intramedullary infection. The present study investigated the use of systemic gentamicin in addition to a controlled local release from a highly lipophilic gentamicinpalmitate compound while the previous study showed efficacy of sole antibiotic implant-coating.', 'Forty male Sprague-Dawley rats were divided into two groups receiving an intramedullary femoral injection of 10(2) CFU of a common methicillin susceptible Staphylococcus aureus strain (MSSA Rosenbach). Group I received an uncoated implant whereas group II received a coated implant. All animals received a single shot intraperitoneal application of gentamicinsulfate directly after wound closure while the historical control group III (n\xa0=\xa020) had no antibiotic treatment at all. Animals were observed for 28 and 42\xa0days. Serum haptoglobin and relative weight gain were assessed as well as roll over cultures of explanted femur nails and histological scores of periprosthetic infection in dissected femora.', 'Systemic application of gentamicin combined with antibiotic-coated implant did not further reduce bacterial growth significantly compared with systemic or local antibiotic application alone. Combined local and systemic therapy reduced serum haptoglobin significantly after day 7, 28 and 42 whereas systemic application alone did not compare to controls.\Question: Does systemic antibiotic therapy significantly improve outcome in a rat model of implant-associated osteomyelitis induced by Methicillin susceptible Staphylococcus aureus?


Output: Systemic perioperative and implant-associated application of antibiotics were both comparably effective to treat implant-associated infections whereas the combined antibiotic therapy further reduced systemic signs of infection time dependent.