EGFR is frequently mutated and amplified in lung adenocarcinomas sensitive to EGFR inhibitors gefitinib and erlotinib. A secondary mutation, T790M, has been associated with acquired resistance but ...has not been shown to be sufficient to render EGFR mutant/amplified lung cancers resistant to EGFR inhibitors. We created a model for studying acquired resistance to gefitinib by prolonged exposure of a gefitinib-sensitive lung carcinoma cell line (H3255; EGFR mutated and amplified) to gefitinib in vitro. The resulting resistant cell line acquired a T790M mutation in a small fraction of the amplified alleles that was undetected by direct sequencing and identified only by a highly sensitive HPLC-based technique. In gefitinib-sensitive lung cancer cells with EGFR mutations and amplifications, exogenous introduction of EGFR T790M effectively conferred resistance to gefitinib and continued ErbB-3/PI3K/Akt signaling when in cis to an activating mutation. Moreover, continued activation of PI3K signaling by the PIK3CA oncogenic mutant, p110alpha E545K, was sufficient to abrogate gefitinib-induced apoptosis. These findings suggest that allelic dilution of biologically significant resistance mutations may go undetected by direct sequencing in cancers with amplified oncogenes and that restoration of PI3K activation via either a T790M mutation or other mechanisms can provide resistance to gefitinib.
The article presents a theoretical rationale and a clinical case of relief of post-COVID ventilation failure by inhalation of Xe and O
gas mixture. Pneumonitis of coronavirus etiology transforms ...saturated phospholipids of surfactant into a solid-ordered phase, which disrupts surface tension, alveolar pneumatization, and alveolar-capillary gas exchange. Using molecular modeling (B3LYP/lanl2dz; GAUSSIAN09), we demonstrated that Xe atom due to the van der Waals dispersion interaction increases the distance between the phospholipid acyl chains providing a phase transition from the solid-ordered to liquid phase and restored the surface-active monolayer surfactant film. A clinical case confirmed that short-term inhalations of the Xe and O
gas mixture relieved manifestations of ventilation insufficiency and increased SpO
and pneumatization of the terminal parts of the lungs.
The article presents a theoretical rationale and a clinical case of relief of post-COVID ventilation failure by inhalation of Xe and O
2
gas mixture. Pneumonitis of coronavirus etiology transforms ...saturated phospholipids of surfactant into a solid-ordered phase, which disrupts surface tension, alveolar pneumatization, and alveolar-capillary gas exchange. Using molecular modeling (B3LYP/lanl2dz; GAUSSIAN09), we demonstrated that Xe atom due to the van der Waals dispersion interaction increases the distance between the phospholipid acyl chains providing a phase transition from the solid-ordered to liquid phase and restored the surface-active monolayer surfactant film. A clinical case confirmed that short-term inhalations of the Xe and O
2
gas mixture relieved manifestations of ventilation insufficiency and increased SpO
2
and pneumatization of the terminal parts of the lungs.
The condensation of trinuclear rhenium bromide with lead sulfide yields the (H
9
O
4
)
2
Re
6
S
6
Br
8
octahedral cluster complex isolated from the HBr/EtOH mixture in the form of the acid. (H
9
O
4
...)
2
Re
6
S
6
Br
8
crystallizes in the
P
2
1
/
c
space group,
a
= 9.2010(2) Å,
b
= 9.1508(2) Å,
c
= 17.3759(3) Å, γ = 101.817(1)°. Thermal decomposition of the complex at a moderate temperature (350 °C) results in a metastable Re
6
S
6
Br
6
compound, which is not formed in the ternary Re–S–Br system at high temperatures. This compound is X-ray amorphous; its structure is determined based on the X-ray photoelectron and Raman spectroscopy data.
Studies on rats (
n
= 12) addressed reactive changes to astrocytes in the nucleus accumbens of the forebrain after global cerebral ischemia induced by bilateral occlusion of both common carotid ...arteries, this being a frequently used model for assessing the efficacies of pharmacological substances with antiischemic and neuroprotective properties. In these conditions, the nucleus accumbens is within the partial ischemia zone. Morphometric investigations of the nucleus accumbens were performed in three groups of rats (four animals in each group): after ligation of both common carotid arteries, after sham operation, and in intact animals. Astrocytes were detected on serial sections using the reaction for glial fibrillary acidic protein with hematoxylin counterstaining. At seven days after surgery, astrocyte counts were made for each animal using seven sequential squares (each of 0.01 mm
2
); the distances between astrocyte bodies and the walls of capillaries within a radius of 20 μm were measured, as were the areas of the cell bodies and the lengths of their main processes. Nucleus accumbens astrocytes in the seven-day bilateral common carotid artery occlusion model were exposed to a state of partial ischemia. Their reactive changes consisted of cytotoxic edema, with damage to intermediate filament proteins in the bodies, processes, and perivascular glial membranes. Concentration of astrocyte bodies close to blood capillaries operated as an adaptive mechanism and was a condition for cell survival in conditions of restricted brain blood flow.
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•Re6Q8(CN)64– (Q = S, Se) or Re6S8(CN)4(OH)24– octahedral clusters.•H bonded molecular networks.•Charge Assisted H-Bonding.
The combination of 1,4-diamidiniumbenzene cation of H2DAB ...with Re6Q8(CN)64– (Q = S, Se) or Re6S8(CN)4(OH)24– leads to solid-state compounds of formula (H2DAB)2Re6Q8(CN)6∙nH2O (Q = S, n = 2.5 (1) or Q = Se, n = 2 (2)), and (HDAB)2Re6S8(CN)4(H2O)2∙7H2O (3). Two isostructural compounds are formed through the monohapto recognition mode between H bond donors (H2DAB2+) and H bond acceptors (the –CN moieties of the cluster anions). A 2D system involving water molecules was formed, whereas with the disordered Re6S8(CN)4(H2O)22– anion, a deformed diamondoid porous compound was obtained. Moreover, amidinium cation becomes partially deprotonated (HDAB+). These are rare examples of reliable charge assisted H bonded network involving Re cyanide clusters.
CsLnZnS
3
(Ln = Gd, Dy) crystals are obtained by the interaction of metal sulfides in the cesium iodide melt. It is found that these compounds are isostructural, belong to the KCuZrS
3
structure ...type, and crystallize in the space group
Cmcm
with the parameters
a
= 4.010(5) Å,
b
= 15.32(3) Å,
c
= 10.542(19) Å for CsGdZnS
3
and
a
= 4.0106(3) Å,
b
= 15.2493(12) Å,
c
= 10.5978(8) Å for CsDyZnS
3
. The structures of these compounds consist of {LnS
6
} octahedra and {ZnS
4
} tetrahedra, which by sharing edges, form charged
2∞
{LnZnS
3
}
–
layers separated by Cs
+
ions. Band gaps of these compounds are determined as 3.70 eV and 3.84 eV for CsGdZnS
3
and CsDyZnS
3
respectively.
Single crystals of a solid solution of the (Y
1–
x
Eu
x
)
2
O
3
compound with the bixbyite-type structure and different europium contents, which are suitable for the structural analysis, are grown by ...the flux method. The structural data show that the Y/Eu occupation of independent sites is uniform in the crystal; europium has no preferred site occupancy. The average
R
–O distance is also typical of the rare-earth metal atoms located at different crystallographic sites and increases monotonically as the europium content increases in the crystal. The europium distribution coefficient from the flux is noticeably less than unity, which enriches the crystal with yttrium compared to the flux.
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