The platinum–acridine anti-cancer agent [PtCl(en)(LH)](NO3)2 (1) (en = ethane-1,2-diamine, LH = N-(2-(acridin-9-ylamino)ethyl)-N-methylpropionimidamide, acridinium cation) and the clinical drug cisplatin were studied in chemoresistant non-small cell lung cancer (NSCLC) cell lines for their cytotoxic potency and cell-kill mechanisms. In the three cell lines tested (NCI-H460, NCI-H522, and NCI-H1435) compound 1 shows a pronounced cytotoxic enhancement of 40–200-fold compared to cisplatin at inhibitory concentrations reaching the low-nanomolar range. Based on changes in cell adhesion and cell morphology, monitored in real time by impedance measurements, compound 1 kills NCI-H460 cells significantly more efficiently than cisplatin at equitoxic concentrations. Flow cytometry analysis of NCI-H460 cells reveals a robust S-phase arrest of cells treated with compound 1, whereas cells treated with cisplatin progress to G2/M of the cell cycle. A pronounced inhibition of DNA replication in 75% of viable cells is observed in NCI-H460 cells treated with compound 1 at an IC90 molar concentration for 48 h, based on the reduced incorporation of the fluorophore-clickable nucleoside analogue 5-ethynyl-2´-deoxyuridine (EdU) into newly synthesized DNA. The distinct cell-cycle perturbations and cell-kill potential of compound 1 are discussed in the light of the DNA interactions of this agent and its potential to overcome cisplatin resistance in NSCLC.

Context. There has been a sustained debate in the medical literature over whether physicians should engage with patients' religious and spiritual concerns. Objectives. This study explores what physicians believe about the relative importance and appropriateness of engaging with patients' spiritual concerns and physicians' choices of interventions. Methods. In 2010, a questionnaire was mailed to 2016 U.S. physicians with survey items querying about the relative importance of addressing patients' spiritual concerns at the end of life and the appropriateness of interventions in addressing those concerns. The survey also contained an experimental vignette to assess physicians' willingness, if asked by patients, to participate in prayer. Results. Adjusted response rate was 62% (1156/1878). The majority of physicians (65%) believe that it is essential to good practice for physicians to address patients' spiritual concerns at the end of life. Physicians who were more religious were more likely to believe that spiritual care is essential to good medical practice (odds ratio: 2.76, 95% CI 1.12e6.81) and believe that it is appropriate to always encourage patients to talk to a chaplain (odds ratio: 5.71, 95% CI: 2.28e14.3). A majority of the physicians (55%) stated that, if asked, they would join the family and patient in prayer. Physicians' willingness to join ranged from 67% when there was concordance between the physician's and the patient's religious affiliation to 51% when there was discordance. Conclusion. The majority of U.S. physicians endorse a limited role in the provision of spiritual care, although opinions varied based on physicians' religious characteristics.