instruction:
Given a passage, 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.
question:
A severe complication in the replacement therapy of hemophilia A (HA) patients is the development of alloantibodies (inhibitors) against factor VIII, which neutralizes the substituted factor. The primary genetic risk factors influencing the development of inhibitors are F8 gene mutations. Interleukins and cytokines that are involved in the regulation of B-lymphocyte development are other possible targets as genetic risk factors. This study assesses the possible involvement of 9 selected single nucleotide gene polymorphisms (SNPs) with interleukins (IL-4, IL-5, and IL-10), transforming growth factor beta 1 (TGF-β1), and interferon gamma (IFN-γ) in inhibitor development in severely affected HA patients carrying a null mutation in the F8 gene.', 'A total of 173 HA patients were screened for intron 22 inversion and null mutations (nonsense and deletions). Genotyping of a total of 9 SNPs in genes IL-4, IL-5, IL-10, TGF-β1, and IFN-γ in 103 patients and 100 healthy individuals was carried out.', 'An association analysis between 42 inhibitor (+) and 61 inhibitor (-) patients showed a significant association with the T allele of rs2069812 in the IL-5 gene promoter and patients with inhibitors (p=0.0251). The TT genotype was also significantly associated with this group with a p-value of 0.0082, odds ratio of about 7, and confidence interval of over 90%, suggesting that it is the recessive susceptibility allele and that the C allele is the dominant protective allele.
answer:
Is a Polymorphism in the IL-5 Gene Associated with Inhibitor Development in Severe Hemophilia A Patients?


question:
Prevention of intraabdominal abscess formation constitutes an important goal in treatment of secondary peritonitis. Fibrinolytic therapy may be effective in this respect. The efficacy of recombinant tissue plasminogen activator (rtPA) and urokinase is compared in a preclinical model for surgical treatment of peritonitis.', 'Peritonitis was induced by intraperitoneal bacterial challenge in male Wistar rats. After 1 hour, surgery was performed. Four groups (n = 20) were treated with one of the following: rtPA, urokinase, streptokinase (a negative protein control), or saline. Blood cultures were taken at 6 and 24 hours; cell counts and cytokine measurements were performed in peritoneal fluid at 1, 3 and 5 days. After 5 days, animals were killed and intraperitoneal abscess formation was analyzed.', 'Both rtPA and urokinase strongly (> 75%) and significantly (P < .05) reduced abscess formation without negative side effects. No bleeding complications were observed. Fibrinolytic therapy altered the intraperitoneal cellular distribution (less neutrophils and more macrophages) but did not essentially alter the courses of interleukin-6 and interleukin-10 (decreasing in time) or tumor necrosis factor-* (increasing in time) levels.
answer:
Do both tissue-type plasminogen activator and urokinase prevent intraabdominal abscess formation after surgical treatment of peritonitis in the rat?


question:
Temozolomide (TMZ) is an oral DNA-alkylating agent used for treating patients with glioblastoma. However, therapeutic benefits of TMZ can be compromised by the expression of O6-methylguanine methyltransferase (MGMT) in tumor tissue. Here we used MGMT-expressing glioblastoma stem cells (GSC) lines as a model for investigating the molecular mechanism underlying TMZ resistance, while aiming to explore a new treatment strategy designed to possibly overcome resistance to the clinically relevant dose of TMZ (35\xa0μM).', 'MGMT-expressing GSC cultures are resistant to TMZ, and IC50 (half maximal inhibitory concentration) is estimated at around 500\xa0μM. Clonogenic GSC surviving 500\xa0μM TMZ (GSC-500\xa0μM TMZ), were isolated. Molecular signatures were identified via comparative analysis of expression microarray against parental GSC (GSC-parental). The recombinant protein of top downregulated signature was used as a single agent or in combination with TMZ, for evaluating therapeutic effects of treatment of GSC.', 'The molecular signatures characterized an activation of protective stress responses in GSC-500\xa0μM TMZ, mainly including biotransformation/detoxification of xenobiotics, blocked endoplasmic reticulum stress-mediated apoptosis, epithelial-to-mesenchymal transition (EMT), and inhibited growth/differentiation. Bone morphogenetic protein 7 (BMP7) was identified as the top down-regulated gene in GSC-500\xa0μM TMZ. Although augmenting BMP7 signaling in GSC by exogenous BMP7 treatment did not effectively stop GSC growth, it markedly sensitized both GSC-500\xa0μM TMZ and GSC-parental to 35\xa0μM TMZ treatment, leading to loss of self-renewal and migration capacity. BMP7 treatment induced senescence of GSC cultures and suppressed mRNA expression of CD133, MGMT, and ATP-binding cassette drug efflux transporters (ABCB1, ABCG2), as well as reconfigured transcriptional profiles in GSC by downregulating genes associated with EMT/migration/invasion, stemness, inflammation/immune response, and cell proliferation/tumorigenesis. BMP7 treatment significantly prolonged survival time of animals intracranially inoculated with GSC when compared to those untreated or treated with TMZ alone (p\u2009=\u20090.0017), whereas combination of two agents further extended animal survival compared to BMP7 alone (p\u2009=\u20090.0489).
answer:

Does bone morphogenetic protein 7 sensitize O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide?