Characterization of Locally Excited and Charge-Transfer States of the Anticancer Drug Lapatinib by Ultrafast Spectroscopy and Computational Studies
CHEMISTRY-A EUROPEAN JOURNAL
Authors: Vaya, Ignacio; Andreu, Inmaculada; Lence, Emilio; Gonzalez-Bello, Concepcion; Consuelo Cuquerella, M.; Navarrete-Miguel, Miriam; Roca-Sanjuan, Daniel; Miranda, Miguel A.
Abstract
Lapatinib (LAP) is an anticancer drug, which is metabolized to theN- and O-dealkylated products (N-LAP andO-LAP, respectively). In view of the photosensitizing potential of related drugs, a complete experimental and theoretical study has been performed on LAP,N-LAP andO-LAP, both in solution and upon complexation with human serum albumin (HSA). In organic solvents, coplanar locally excited (LE) emissive states are generated; they rapidly evolve towards twisted intramolecular charge-transfer (ICT) states. By contrast, within HSA only LE states are detected. Accordingly, femtosecond transient absorption reveals a very fast switching (ca. 2 ps) from LE (lambda(max)=550 nm) to ICT states (lambda(max)=480 nm) in solution, whereas within HSA the LE species become stabilized and live much longer (up to the ns scale). Interestingly, molecular dynamics simulation studies confirm that the coplanar orientation is preferred for LAP (or to a lesser extentN-LAP) within HSA, explaining the experimental results.
Diagnostic Yield of Staging Brain MRI in Patients with Newly Diagnosed Non-Small Cell Lung Cancer
RADIOLOGY
Authors: Kim, Minjae; Suh, Chong Hyun; Lee, Sang Min; Kim, Ho Cheol; Aizer, Ayal A.; Yanagihara, Ted K.; Bai, Harrison X.; Guenette, Jeffrey P.; Huang, Raymond Y.; Kim, Ho Sung
Abstract
Background: Existing guidelines are inconsistent regarding the indications for staging brain MRI in patients with newly diagnosed, early-stage non-small cell lung cancer (NSCLC). Purpose: To evaluate the diagnostic yield of staging brain MRI in the initial evaluation of lung cancer. Materials and Methods: This retrospective, observational, single-institution study included patients with newly diagnosed NSCLC who underwent staging chest CT and staging brain MRI from November 2017 to October 2018. Diagnostic yield was defined as the proportion of patients with brain metastases among all patients. Yield was stratified into clinical stage groups per the eighth edition of the American Joint Committee on Cancer staging guidelines, based on staging chest CT and in adenocarcinoma with epidermal growth factor receptor (EGFR) gene mutation and anaplastic lymphoma kinase (ALK) gene rearrangement. Subgroup analyses were performed on the basis of cell types and molecular markers. The chi(2) test was performed to compare the diagnostic yields, and Bonferroni correction was used to account for multiple testing between stage groups. Results: A total of 1712 patients (mean age, 64 years 6 10 [standard deviation]; 1035 men) were included. The diagnostic yield of staging brain MRI in newly diagnosed NSCLC was 11.9% (203 of 1712; 95% confidence interval [CI]: 10.4%, 13.5%). In clinical stage IA, IB, and II disease, the diagnostic yields were 0.3% (two of 615; 95% CI: 0.0%, 1.2%), 3.8% (seven of 186; 95% CI: 1.5%, 7.6%), and 4.7% (eight of 171; 95% CI: 2.0%, 9.0%), respectively. The diagnostic yield was higher in patients with adenocarcinoma (13.6%; 176 of 1297; 95% CI: 11.8%, 15.6%) than squamous cell carcinoma (5.9%; 21 of 354; 95% CI: 3.7%, 8.9%) and in patients with EGFR mutation-positive adenocarcinoma (17.5%; 85 of 487; 95% CI: 14.2%, 21.1%) than with EGFR mutation negative adenocarcinoma (10.6%; 68 of 639; 95% CI: 8.4%, 13.3%) (P<.001 for both). Conclusion: The diagnostic yield of staging brain MRI in clinical stage IA non-small cell lung cancer was low, but staging brain MRI had a higher diagnostic yield in clinical stage IB and epidermal growth factor receptor mutation-positive adenocarcinoma. (C) RSNA, 2020