Epidermal growth factor receptor mutation in combination with expression of MIG6 alters gefitinib sensitivity

<p>Abstract</p> <p>Background</p> <p>Epidermal growth factor receptor (EGFR) signaling plays an important role in the regulation of cell proliferation, survival, metastasis, and invasion in various tumors. Earlier studies showed that the EGFR is frequently overexpressed in non-small-cell lung cancer (NSCLC) and EGFR mutations at specific amino acid residues in the kinase domain induce altered responsiveness to gefitinib, a small molecule EGFR tyrosine kinase inhibitor. However, the mechanism underlying the drug response modulated by EGFR mutation is still largely unknown. To elucidate drug response in EGFR signal transduction pathway in which complex dynamics of multiple molecules involved, a systematic approach is necessary. In this paper, we performed experimental and computational analyses to clarify the underlying mechanism of EGFR signaling and cell-specific gefitinib responsiveness in three H1299-derived NSCLC cell lines; H1299 wild type (H1299WT), H1299 with an overexpressed wild type EGFR (H1299EGFR-WT), and H1299 with an overexpressed mutant EGFR L858R (H1299L858R; gefitinib sensitive mutant).</p> <p>Results</p> <p>We predicted and experimentally verified that Mig6, which is a known negative regulator of EGFR and specifically expressed in H1299L858R cells, synergized with gefitinib to suppress cellular growth. Computational analyses indicated that this inhibitory effect is amplified at the phosphorylation/dephosphorylation steps of MEK and ERK.</p> <p>Conclusions</p> <p>Thus, we showed that L858R receptor mutation in combination with expression of its negative regulator, Mig6, alters signaling outcomes and results in variable drug sensitivity.</p

Physical properties of a new cuprate superconductor Pr_2Ba_4Cu_7O_{15-\delta}

We present studies of the thermal, magnetic and electrical transport properties of reduced polycrystalline Pr_2Ba_4Cu_7O_{15-\delta} (Pr247) showing a superconducting transition at Tc = 10 - 16 K and compare them with those of as-sintered non-superconducting Pr247. The electrical resistivity in the normal state exhibited T2 dependence up to approximately 150 K. A clear specific heat anomaly was observed at Tc for Pr247 reduced in a vacuum for 24 hrs, proving the bulk nature of the superconducting state. By the reduction treatment, the magnetic ordering temperature TN of Pr moments decreased from 16 to 11 K, and the entropy associated with the ordering increased, while the effective paramagnetic moments obtained from the DC magnetic susceptibility varied from 2.72 to 3.13 mB. The sign of Hall coefficient changed from positive to negative with decreasing temperature in the normal state of a superconducting Pr247, while that of as-sintered one was positive down to 5 K. The electrical resistivity under high magnetic fields was found to exhibit T^a dependence (a = 0.08 - 0.4) at low temperatures. A possibility of superconductivity in the so-called CuO double chains is discussed.Comment: Science and Technology of Advanced Materials (in press

Epithelioid granuloma mimicking lung cancer showed intense uptake on [18F]FAPI-74 PET

The version of record of this article, first published in European Journal of Nuclear Medicine and Molecular Imaging, is available online at Publisher’s website: https://doi.org/10.1007/s00259-023-06478-

Abnormal localized [¹⁸F]FDG accumulation in a Hoffman 3D brain phantom caused by Pseudomonas aeruginosa and Stenotrophomonas maltophilia

The version of record of this article, first published in European Journal of Nuclear Medicine and Molecular Imaging, is available online at Publisher’s website: https://doi.org/10.1007/s00259-024-06816-5.Hoffman 3D brain phantom was scanned to standardize the image quality in a clinical trial. Dynamic [¹⁸F]fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG PET), which started 15 min after being filled with [¹⁸F]FDG (25 MBq), revealed an abnormally increasing accumulation of [¹⁸F]FDG in the left occipital cortex region at one hour. This abnormal accumulation showed an increasing trend (Fig. 1A, B). The presence of bacteria was suggested by the culture of scrabbed samples taken from the corresponding region in the phantom, later confirmed to be Pseudomonas aeruginosa and Stenotrophomonas maltophilia (Fig. 1C). Pseudomonas aeruginosa is an aerobic Gram-negative rod with a single flagellum at one end. It is a facultative anaerobic bacterium that generates ATP (adenosine triphosphate) necessary for growth by aerobic respiration and grows by oxidative degradation of glucose in the presence of oxygen [1]. Stenotrophomonas maltophilia is a non-fermentative Gram-negative bacterium that consumes proteins and peptides rather than sugars and carbohydrates as carbon and nutrient sources [2]. There have been several reports on the uptakes of [¹⁸F]FDG [3, 4]. We concluded that the abnormal accumulation was caused by FDG-avid bacterium, Pseudomonas aeruginosa and Stenotrophomonas maltophilia.It is preferable to use degassed tap water rather than purified or distilled water to prevent the growth of bacteria. Hoffman 3D brain phantom should be disassembled and completely dried after the scan, especially for multicenter clinical trials