BackgroundWe recently demonstrated the cytotoxicity of liquid crystal precursors (hereafter referred to as “mesogenic compounds”) in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy. To develop more effective and cancer-specific agents, in this study, we investigated the structure–activity relationships of mesogenic compounds with cytotoxic effects against multiple NSCLC cells.MethodsThe pharmacological effects of mesogenic compounds were examined in human NSCLC cells (A549, LU99, EBC-1, and H1299) and normal WI-38 human fibroblast. Analyses of the cell cycle, cell-death induction, and capsases expression were performed.ResultsThe 3-ring compounds possessing terminal alkyl and hydroxyl groups (compounds C1–C5) showed cytotoxicity in NSCLC cells regardless of the p53 status. The compounds C1 and C3, which possess a pyrimidine at the center of the core, induced G2/M arrest, while the compounds without a pyrimidine (C2, C4, and C5) caused G1 arrest; all compounds produced caspase-mediated cell death. These events occurred in a p53-independent manner. Furthermore, it was suggested that compounds induced cell death through p53-independent DNA damage-signaling pathway. Compounds C2, C4, and C5 did not show strong cytotoxicity in WI-38 cells, whereas C1 and C3 did. However, the cytotoxicity of compound C1 against WI-38 cells was improved by modulating the terminal alkyl chain lengths of the compound.ConclusionsWe showed the p53-indepdent structure–activity relationships of mesogenic compounds related to the cytotoxic effects. These structure–activity relationships will be helpful in the development of more effective and cancer-specific agents.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2585-6) contains supplementary material, which is available to authorized users.
Epidural administration of 3 mg of synthetic [3-endorphin produced analgesia in 10 patients with intractable pain due to disseminated cancer. Mean onset of relief of pain was 24 ---3 minutes and the mean duration of analgesia was 19 --+ 3 hours.The onset of analgesia produced by the epidural injection of [3-endorphin was slower and the duration less than those observed after intrathecal injection.KEY WORDS: ANALGESIA, epidura113-endorphin; PAIN.WE HAVE REPORTED previously profound and long-lasting analgesia from the intrathecal administration of 3 mg synthetic 13-endorphin, the most potent of the opioid peptides, in patients with intractable pain due to disseminated can-This communication is concerned with recent observations of analgesia produced by the epidural administration of synthetic 13-endorphin in 10 patients with intractable pain from disseminated cancer. No respiratory depression, hypotension, hypothermia, or catatonia was observed.
METHODSynthetic 13-endorphin 3 mg in 10 ml of physiological saline, sterilised by Millipore filter, was injected epidurally at the appropriate lumbar interspace. Ten patients with chronic intractable pain in the back, chest, abdomen, hip and thigh regions secondary to metastic malignancies were selected for study. Informed consent was obtained. Systemic analgesics were withheld at least five hours before adminsitration of [3-endorphin. The visual pain scale was explained to each patient and baseline pain intensity was determined 30 min before the epidural injection. In a single-blind randomised trial one physician administered successively 13-endorphin or physiological saline to seven patients; the others received only [3-endorphin, without placebo.The (3-endorphin used here was synthesized as previously described, 1'2 by Dr.
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