Different subtypes of EGFR exon 19 and 21 mutations exhibited differential survival to first-line TKI therapy. Detailed sequence evaluation of exon 19 deletions may provide important prognostic information on survival outcome after TKI.

By using synthetic oligonucleotides as probes, plasmid clones containing portions of cDNA coding for human C4b-binding protein were isolated from a liver cDNA library. The entire amino acid sequence of the C4b-binding protein can be predicted from this study of the cloned cDNA when allied to a previous sequence study at the protein level [Chung, Gagnon & Reid (1985) Mol. Immunol. 22, 427-435], in which over 55% of the amino acid sequence, including the N-terminal 62 residues, was obtained. The plasmid clones isolated allowed the unambiguous determination of 1717 nucleotides of cDNA sequence between the codon for the 32nd amino acid in the sequence of C4b-binding protein and the 164th nucleotide in the 3' non-translated region. The sequence studies show that the secreted form of C4b-binding protein, found in plasma, is composed of chains of apparent Mr 70 000 that contains 549 amino acid residues. Examination of the protein and cDNA sequence results show that there are at least two polymorphic sites in the molecule. One is at position 44, which can be glutamine or threonine, and the other is at position 309, which can be tyrosine or histidine. Northern-blot analysis indicated that the mRNA for C4b-binding protein is approx. 2.5 kilobases long. The N-terminal 491 amino acids of C4b-binding protein can be divided into eight internal homologous regions, each approx. 60 amino acids long, which can be aligned by the presence in each region of four half-cystine, one tryptophan and several other conserved residues. These regions in C4b-binding protein are homologous with the three internal-homology regions that have been reported to be present within the Ba region of the complement enzyme factor B and also to the internal-homology regions found in the non-complement beta 2-glycoprotein I.

Verdrehte Organisation: Die Pyrolyse von Filmen eines Komposits aus nanokristalliner Cellulose (NCC) und Kieselgel ergibt mesoporöse Kohlenstoffmaterialien mit weitreichender chiraler Organisation (siehe Bild). NCC fungiert als Templat, und das Kohlenstoffprodukt hat eine hohe spezifische Oberfläche (>1400 m2 g−1) und repliziert exakt die linksgängige Helixstruktur der chiral‐nematischen NCC‐Filme.

No abstract

The discovery of the novel KIF5B-ALK variant further consolidated the role of aberrant ALK signaling in lung carcinogenesis.

Epidermal growth factor receptor (EGFR) mutations are common in lung adenocarcinomas, especially from nonsmoking women of Asian descent. We have previously shown EGFR mutations occur in >70% of lung adenocarcinoma from nonsmokers in our population with a complex mutational profile, including 13% of EGFR double mutations. In this study, we investigated the in vitro gefitinib response of four EGFR double mutants identified in untreated patients, including Q787R+L858R, E709A+G719C, T790M+L858R, and H870R+L858R. The phosphorylation profiles of EGFR and downstream effectors AKT, STAT3/5, and ERK1/2 were compared by immunoblot analyses among the single and double mutants transfected into H358 cells. Results showed that mutants responded to in vitro gefitinib treatment with different sensitivities. The G719C and L858R single mutants showed the highest gefitinib sensitivity compared with the corresponding coexisting single mutants E709A, Q787R, H870R, and T790M. The double mutants E709A+G719C, Q787R+L858R, and H870R+L858R showed attenuated responses to gefitinib in the EGFR and downstream effector phosphorylation profiles compared with G719C or L858R alone. T790M+L858R showed strong resistance to gefitinib. Clinically, the patient whose tumor contained H870R+L858R showed tumor stabilization by 250 mg oral gefitinib daily but cerebral metastasis developed 6 months later. Correlation with the in vitro phosphorylation profile of H870R +L858R suggested that treatment failure was probably due to inadequate suppression of EGFR signaling by the drug level attainable in the cerebrospinal fluid at the given oral dosage. Overall, the findings suggested that rare types of EGFR substitution mutations could confer relative gefitinib resistance when combined with the common activating mutants. [Mol Cancer Ther

No abstract

The CD4 antigen is a plasma membrane glycoprotein of^-55 kD that is expressed on most thymocytes and on Th cells in all mammalian species examined, including human, rat, mouse, sheep, and pig (1) . The antigen is also present on rat macrophages (MO) and human monocytes in a similar molecular form (2, 3) . Studies with mAbs (4) have demonstrated that CD4 on Th cells is an important accessory molecule involved in recognition of antigen plus MHC class II molecules during immune responses . In humans, a more recently defined property of the CD4 antigen is to act as the receptor for the AIDS virus (human immunodeficiency virus or HIV) (5) . Although nothing is known concerning the the regulation and functional significance of CD4 expression on MO, its presence is likely to be at least one reason why these cells become infected by HIV (6, 7) . Here we demonstrate that, unlike human and rat M0, mouse Mo do not express the CD4 (L3T4) antigen . This species disparity indicates, firstly, that CD4 may not be essential for Mo function, and secondly, that MO regulate CD4 expression differently from Th cells . Volume 166 August 1987 613-618 Materials and Methods BriefDefinitive ReportAnimals. Specific pathogen-free C57BL/6 mice and AO rats were bred at the Sir William Dunn School of Pathology and both sexes were used between 6 and 12 wk of age .Antibodies. The following rat mAbs to mouse CD4 (L3T4) were obtained as shown and used as tissue culture supernatants at saturation : H129 .19 (IgG2a) (8), RL 172 .4 (IgM) (9), and GK1 .5 (IgG2b) (10), provided by Dr . H . R . MacDonald, Ludwig Institute for Cancer Research, Lausanne, Switzerland; and YTS 191 .1 (IgG2b) and YTA .3 (IgG2b) (11), provided by Dr . S . P . Cobbold, Department of Pathology, Cambridge University, Cambridge, United Kingdom . The noncompeting mouse anti-rat CD4 (W3/25) mAbs, W3/25 (IgGI) and MRC OX-35 (IgG2a) (2), were from the MRC Cellular Immunology Research Unit, University of Oxford, Oxford, United Kingdom . Other mAbs used were MRC OX-21 (IgGI), a mouse mAb to human C3b inactivator (2), and F4/80 (IgG2b), a rat mAb specific for mature mouse Mo (12) .Labeling of Cells with Antibodies . Mouse and rat resident peritoneal MO were purified by adherence for 1 h to bacteriologic petri dishes followed by extensive washing . The adherent cells (>90% Mo by morphology) were detached by a 15-min incubation in calcium-and magnesium-free PBS at 37°C followed by gentle pipetting . Thymocytes