Src-Homology 2 Domain-Containing Phosphatase 2 in Resected EGFR Mutation-Positive Lung Adenocarcinoma

Funding: supported by a La Caixa Foundation grant and the Spanish Association Against Cancer (PROYE18012ROSE)EGFR mutation-positive lung adenocarcinoma (LUAD) displays impaired phosphorylation of ERK and Src-homology 2 domain-containing phosphatase 2 (SHP2) in comparison with EGFR wild-type LUADs. We hypothesize that SHP2 expression could be predictive in patients positive with resected EGFR mutation versus patients with EGFR wild-type LUAD. We examined resected LUAD cases from Japan and Spain. mRNA expression levels of AXL, MET, CDCP1, STAT3, YAP1, and SHP2 were analyzed by quantitative reverse transcriptase polymerase chain reaction. The activity of SHP2 inhibitors plus erlotinib were tested in EGFR -mutant cell lines and analyzed by cell viability assay, Western blot, and immunofluorescence. A total of 50 of 100 EGFR mutation-positive LUADs relapsed, among them, patients with higher SHP2 mRNA expression revealed shorter progression-free survival, in comparison with those having low SHP2 mRNA (hazard ratio: 1.83; 95% confidence interval: 1.05-3.23; p = 0.0329). However, SHP2 was not associated with prognosis in the remaining 167 patients with wild-type EGFR. In EGFR -mutant cell lines, the combination of SHP099 or RMC-4550 (SHP2 inhibitors) with erlotinib revealed synergism via abrogation of phosphorylated AKT (S473) and ERK1/2 (T202/Y204). Although erlotinib translocates phosphorylated SHP2 (Y542) into the nucleus, either RMC-4550 alone, or in combination with erlotinib, relocates SHP2 into the cytoplasm membrane, limiting AKT and ERK1/2 activation. Elevated SHP2 mRNA levels are associated with recurrence in resected EGFR mutation-positive LUADs, but not in EGFR wild-type. EGFR tyrosine kinase inhibitors can enhance SHP2 activation, hindering adjuvant therapy. SHP2 inhibitors could improve the benefit of adjuvant therapy in EGFR mutation-positive LUADs

Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at root s(NN)=5.02 TeV

The second-order Fourier coefficients (v(2)) characterizing the azimuthal distributions of Y(1S) and Y(2S) mesons produced in PbPb collisions at root s(NN) = 5.02 TeV are studied. The Y mesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb(-1). The scalar product method is used to extract the v2 coefficients of the azimuthal distributions. Results are reported for the rapidity range vertical bar y vertical bar < 2.4, in the transverse momentum interval 0 < pT < 50 GeV/c, and in three centrality ranges of 10-30%, 30-50% and 50-90%. In contrast to the J/psi mesons, the measured v(2) values for the Y mesons are found to be consistent with zero. (C) 2021 The Author(s). Published by Elsevier B.V.Peer reviewe

Future Perspectives on the TNM Staging for Lung Cancer

Since its conception by Pierre Denoix in the mid-20th century, the tumor, node, and metastasis (TNM) classification has undergone seven revisions. The North American database managed by Clifton Mountain was used to inform the 2nd to the 6th editions, and an international database collected by the International Association for the Study of Lung Cancer, promoted by Peter Goldstraw, was used to inform the 7th and the 8th editions. In these two latest editions, it was evident that the impact of tumor size was much greater than it was suggested in previous editions; that the amount of nodal disease had prognostic relevance; and that the number and location of the distant metastases had prognostic implications. However, the TNM classification is not the only prognostic factor. Data are being collected now to inform the 9th edition of the TNM classification, scheduled for publication in 2024. Patient-, environment-, and tumor-related factors, including biomarkers (genetic biomarkers, copy number alterations, and protein alterations) are being collected to combine them in prognostic groups to enhance the prognosis provided by the mere anatomic extent of the tumor, and to offer a more personalized prognosis to an individual patient. International collaboration is essential to build a large and detailed database to achieve these objectives

Pleurodesis química, estudio experimental y correlaciones clínico-experimentales

Tesis doctoral original inédita leída en la Universidad de Autónoma de Madrid, Facultad de Medicina. Fecha de lectura: 15 de diciembre de 198

Foreign-Medical-School Graduates object to the VISA Qualifiying Examination

To the editor; The Visa Qualifying Examination is a two-day test composed of approximately 950 multiple-choice questions conerneing the basic and clinical sciences...

Foreign-Medical-School Graduates object to the VISA Qualifiying Examination

To the editor; The Visa Qualifying Examination is a two-day test composed of approximately 950 multiple-choice questions conerneing the basic and clinical sciences...