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.
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Question: Cetuximab is often combined with radiotherapy in advanced SCCHN. Alternative routes bypassing inhibition of EGFR with cetuximab may overshadow the efficacy of this combination. We undertook this study to investigate a possible role of dasatinib in this scenario.', 'The SCC5, SCC25, SCC29, FaDu and A431 cell lines were assessed in vitro for cell proliferation under cetuximab and dasatinib treatments. In FaDu and A431 cells, dasatinib plus cetuximab resulted in higher proliferation than cetuximab alone. Then, FaDu and A431 cells were implanted into subcutaneous tissue of athymic mice that were irradiated with 30\u2009Gy in 10 fractions over 2 weeks, and treated with cetuximab and dasatinib. Tumour growth, DNA synthesis and angiogenesis were determined. The EGFR, RAS-GTP activity, phosphorylated AKT, ERK1/2, SRC protein levels and VEGF secretion were determined in vitro.', 'The addition of dasatinib to cetuximab and radiotherapy increased tumour growth, DNA synthesis and angiogenesis that were associated with RAS, AKT and ERK1/2 activation, and SRC inhibition in FaDu and A431 cells.

Answer: Does dasatinib worsen the effect of cetuximab in combination with fractionated radiotherapy in FaDu- and A431-derived xenografted tumours?


Question: P53 is a key protein which controls cell cycle arrest and apoptosis in response to DNA damage. Auto-antibodies against p53 have been detected in some cancer patients and also in patients with autoimmune diseases. In these patients, the main cause of anti-p53 antibody occurrence was considered to be increased intracellular p53 protein in cancer cells and autoreactive lymphocytes, respectively. Intracellular p53 also increases with cardiomyocyte apoptosis during heart failure and autoreactive lymphocytes play a role in the course of idiopathic dilated cardiomyopathy (IDC) and ischemic cardiomyopathy (ICM). Based on these observations, we hypothesized that anti-p53 antibody response may also occur in patients with heart failure due to ICM and IDC.', 'The aim of this study was to evaluate anti-p53 antibodies in the serum of patients with heart failure due to IDC and ICM.', '70 eligible patients with heart failure and severe left ventricular systolic dysfunction (mean fractional shortening 12.03 +/- 3.93%) were included in the study. The aetiology of heart failure was IDC in 26 patients and ICM in 44 patients, according to the angiographic and echocardiographic findings.', 'Anti-p53 antibodies were not detected in any of the patients.

Answer: Do serum anti-p53 antibodies occur in patients with heart failure due to idiopathic dilated and ischemic cardiomyopathies?


Question: The antileukemic drug asparaginase, a key component in the treatment of acute lymphoblastic leukemia, acts by depleting asparagine from the blood. However, little is known about its pharmacokinetics and mechanisms of therapy resistance are poorly understood. Here, we explored the in vivo biodistribution of radiolabeled asparaginase, using a combination of in vivo imaging and biochemical techniques, and provide evidence for tissue specific clearance mechanisms, which could reduce effectiveness of the drug at these specific sites.', 'In vivo localization of Indium-111-labeled E.coli asparaginase was carried out in C57Bl/6 mice by both microSPECT/CT and by ex vivo biodistribution studies. Mice were treated with liposomal clodronate to investigate the effect of macrophage depletion on tracer localization and drug clearance in vivo. Moreover, macrophage cell line models RAW264.7 and THP-1, as well as cathepsin B deficient mice, were used to identify the cellular and molecular components controlling asparaginase pharmacokinetics.', 'In vivo imaging and biodistribution studies showed a rapid accumulation of asparaginase in macrophage-rich tissues such as liver, spleen and in particular bone marrow. Clodronate-mediated depletion of phagocytic cells markedly prolonged the serum half-life of asparaginase in vivo and decreased drug uptake in target organs. Immunohistochemistry and in vitro binding assays confirmed the involvement of macrophage-like cells in the uptake of asparaginase. We identified the activity of the lysosomal protease cathepsin B in macrophages as a rate-limiting factor in degrading asparaginase both in vitro and in vivo.

Answer:
Does in vivo imaging of antileukemic drug asparaginase reveal a rapid macrophage mediated clearance from the bone marrow?