New therapeutic approaches in recurrent cervical cancer
Authors: Koensgen, Dominique; Battista, Marco J.; Egger, Eva Katharina; Krajnak, Slavomir; Heimes, Anne-Sophie; Schmidt, Marcus; Keyver-Paik, Mignon-Denise; Hasenburg, Annette; Mustea, Alexander
Background Approved therapeutic options for patients with resistant, recurrent, or metastatic cervical cancer are limited. Objectives Therapeutic agents, for which published results of phase I and II trials are available, will be presented in this review. Materials and methods A selective literature searched was performed in the PubMed. Clinical trials were identified in the database of . Results Inhibitors against programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1), neurotropic tropomyosin receptor kinase (NTRK) gene fusion, poly(ADP-ribose) polymerase (PARP) and targets of the phosphoinositide-3 kinase (PI3K)/AKT/mTOR pathway and therapeutic vaccines against human papillomavirus 16 (HPV16) E6 and E7 antigen were identified. Conclusions Different agents are currently under investigation. The available literature and ongoing trials of the emerging therapeutic approaches will be reviewed concisely. Whether they will enlarge our therapeutic possibilities in advanced cervical cancer remains to be seen. To date, only the PD-1/PD-L1 inhibitor pembrolizumab has been approved by the US Food and Drug Administration (FDA) for advanced cervical cancer.
Nanomolar photodynamic activity of porphyrins bearing 1,4,7-trioxanonyl and 2-methyl-5-nitroimidazole moieties against cancer cells
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
Authors: Wierzchowski, Marcin; Lazewski, Dawid; Tardowski, Tadeusz; Grochocka, Malgorzata; Czajkowski, Rafal; Sobiak, Stanislaw; Sobotta, Lukasz
Despite the continuous development of medicine, there is still a lack of effective and fully safe protocols for the treatment of neoplastic diseases. The drug-drug conjugates approach seems to give a chance to obtain more efficient molecules. New alkoxy and metronidazole substituted porphyrins were synthesized. Novel porphyrins were purified by flash column chromatography and characterized using NMR, MS, UV-Vis and HPLC. The Nuclear Magnetic Resonance study was performed to annotate experimentally observed H-1 NMR and C-13 NMR signals of new compounds. The 2D NMR techniques such as H-1-H-1 COSY (Correlation Spectroscopy), H-1-C-13 HSQC (Heteronuclear Single Quantum Correlation) and H-1-C-13 HMBC (Heteronuclear Multiple Bond Correlation) were used for the structure elucidation of the new compounds. In the range of 250-450 nm of the absorption spectra, the Soret band was observed, whereas the Q band was noted in the range of 500-650 nm. Compounds revealed a fluorescence quantum yield in the range 0.03-0.12. Singlet oxygen generation quantum yields up to 0.54 were determined. Electrochemical properties has also been studied. It has been noticed electropolymerization of compound bearing 5-nitroimidazole substituents. The photodynamic activity of the studied porphyrins against A549 and HEK001/HPV16 cancer cells were examined. The most active against A549 and HEK 001/HPV16 was light-excited trioxanonylporphyrin with the values of IC50 equal to 0.49 mu M and 50 nM respectively.