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: Bortezomib-induced peripheral neuropathy (BIPN) is a significant neurotoxicity, requiring dose reduction or the delay of treatment. In a multicentre trial including 97 % Caucasians and 3 % Asians, BIPN was shown to occur less frequently in cases in which bortezomib was administered subcutaneously. Considering the different pharmacokinetics between Caucasians and Asians, we analysed BIPN according to the administration route, specifically in Korean myeloma patients.', 'We surveyed the prescribed anticonvulsants for the treatment of BIPN and analysed the data after stratifying the results by the cumulative dose of bortezomib. Exclusion criteria were as follows: treated with <2 doses of bortezomib, change in the administration route during the treatment, or receiving anticonvulsants for other reasons prior to bortezomib administration.', 'A total of 101 patients were enrolled; 60 were treated with bortezomib and dexamethasone, and 37 were treated with bortezomib, melphalan, and prednisolone. The median number of treatment courses was four for each regimens. The median exposure to bortezomib for all patients was 19 mg/m(2). Progression-free survival (PFS) and overall survival rates were not statistically different between the groups. There was no difference in the proportion of patients requiring medical treatment (p = 0.388). After stratifying the results, BIPN developed less frequently when bortezomib was administered subcutaneously rather than intravenously in patients receiving more than 23.4 mg/m(2) of bortezomib (p < 0.05).\Question: Is bortezomib-associated peripheral neuropathy requiring medical treatment decreased by administering the medication by subcutaneous injection in Korean multiple myeloma patients?

Output: Since the responses were potent regardless of administration route, the subcutaneous injection of bortezomib should be considered in Asian myeloma patients who are expected to achieve a longer PFS with bortezomib.


Input: Consider Input: Context: The current standard of care for glioblastoma (GBM) involves a combination of surgery, radiotherapy, and temozolomide chemotherapy, but this regimen fails to achieve long-term tumor control. Resistance to temozolomide is largely mediated by expression of the DNA repair enzyme MGMT; however, emerging evidence suggests that inactivation of MSH6 and other mismatch repair proteins plays an important role in temozolomide resistance. Here, we investigate endogenous MSH6 mutations in GBM, anaplastic oligodendroglial tumor tissue, and corresponding brain tumor-initiating cell lines (BTIC).', 'MSH6 sequence and MGMT promoter methylation were determined in human tumor samples and BTICs. Sensitivity to temozolomide was evaluated in vitro using BTICs in the absence and presence of O(6)-benzylguanine to deplete MGMT. The influence of MGMT and MSH6 status on in vivo sensitivity to temozolomide was evaluated using intracranial BTIC xenografts.', 'We identified 11 previously unreported mutations in MSH6 in nine different glioma samples and six paired BTIC lines from adult patients. In addition, MSH6 mutations were documented in three oligodendrogliomas and two treatment-naïve gliomas, both previously unreported findings. These mutations were found to influence the sensitivity of BTICs to temozolomide both in vitro and in vivo, independent of MGMT promoter methylation status.\Question: Do novel MSH6 mutations in treatment-naïve glioblastoma and anaplastic oligodendroglioma contribute to temozolomide resistance independently of MGMT promoter methylation?

Output: These data demonstrate that endogenous MSH6 mutations may be present before alkylator therapy and occur in at least two histologic subtypes of adult glial neoplasms, with this report serving as the first to note these mutations in oligodendroglioma. These findings broaden our understanding of the clinical response to temozolomide in gliomas.


Input: Consider Input: Context: Atherosclerosis is a chronic inflammatory disease. We previously reported that a diet high in alpha-linolenic acid (ALA) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects.', 'The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells (PBMCs) from subjects fed the experimental diets.', 'A randomized, controlled, 3-diet, 3-period crossover study design was used. Hypercholesterolemic subjects (n = 23) were assigned to 3 experimental diets: a diet high in ALA (ALA diet; 6.5% of energy), a diet high in linoleic acid (LA diet; 12.6% of energy), and an average American diet (AAD) for 6 wk. Serum interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) concentrations and the production of IL-6, IL-1beta, and TNF-alpha by PBMCs were measured.', 'IL-6, IL-1beta, and TNF-alpha production by PBMCs and serum TNF-alpha concentrations were lower (P < 0.05 and P < 0.08, respectively) with the ALA diet than with the LA diet or AAD. PBMC production of TNF-alpha was inversely correlated with ALA (r = -0.402, P = 0.07) and with eicosapentaenoic acid (r = -0.476, P = 0.03) concentrations in PBMC lipids with the ALA diet. Changes in serum ALA were inversely correlated with changes in TNF-alpha produced by PBMCs (r = -0.423, P < 0.05).\Question: Does dietary alpha-linolenic acid inhibit proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects?


Output: Increased intakes of dietary ALA elicit antiinflammatory effects by inhibiting IL-6, IL-1beta, and TNF-alpha production in cultured PBMCs. Changes in PBMC ALA and eicosapentaenoic acid (derived from dietary ALA) are associated with beneficial changes in TNF-alpha release. Thus, the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines.