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Six platinum(IV) compounds derived from an oxaliplatin analogue containing the unsaturated cyclic diamine -1,2-diamino-4-cyclohexene (DACHEX), in place of the 1,2-diaminocyclohexane, and a range of axial ligands, were synthesized and characterized. The derivatives with at least one axial chlorido ligand demonstrated solvent-assisted photoreduction. The electrochemical redox behavior was investigated by cyclic voltammetry; all compounds showed reduction potentials suitable for activation in vivo. X-ray photoelectron spectroscopy (XPS) data indicated an X-ray-induced surface reduction of the Pt(IV) substrates, which correlates with the reduction potentials measured by cyclic voltammetry. The cytotoxic activity was assessed in vitro on a panel of human cancer cell lines, also including oxaliplatin-resistant cancer cells, and compared with that of the reference compounds cisplatin and oxaliplatin; all IC values were remarkably lower than those elicited by cisplatin and somewhat lower than those of oxaliplatin. Compared to the other Pt(IV) compounds of the series, the bis-benzoate derivative was by far (5-8 times) the most cytotoxic showing that low reduction potential and high lipophilicity are essential for good cytotoxicity. Interestingly, all the complexes proved to be more active than cisplatin and oxaliplatin even in three-dimensional spheroids of A431 human cervical cancer cells.
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http://dx.doi.org/10.3390/ijms21072325 | DOI Listing |
ACS Pharmacol Transl Sci
December 2024
School of Biological Sciences, University of Utah, Salt Lake City, Utah 84112, United States.
Nicotinic acetylcholine receptors containing the α9 subunit have been mechanistically implicated in alleviating chemotherapy-induced neuropathic pain. However, the cell types that underlie these effects are currently unknown. RgIA-5474 is a recently developed, synthetic α-conotoxin analog that is a potent antagonist of human α9α10 nAChRs.
View Article and Find Full Text PDFSignal Transduct Target Ther
December 2024
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China.
This phase 2/3 trial (NCT04856787) assessed the efficacy and safety of SHR-1701, a bifunctional protein targeting PD-L1 and TGF-β, in combination with BP102 (a bevacizumab biosimilar) and XELOX (capecitabine plus oxaliplatin) as a first-line treatment for unresectable metastatic colorectal cancer (mCRC). In this phase 2 study, a total of 62 patients with untreated, histologically confirmed colorectal adenocarcinoma and no prior systemic therapy for metastatic disease were enrolled. Patients received SHR-1701 (30 mg/kg), bevacizumab (7.
View Article and Find Full Text PDFEur J Cancer
January 2025
Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China. Electronic address:
Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) is almost always fatal after the failure of asparaginase. This phase II study aimed to investigate the efficacy and safety of tislelizumab combined with gemcitabine and oxaliplatin (Tisle-GemOx) in patients with ENKTCL failing asparaginase.
Methods: Eligible patients received Tisle-GemOx as initial induction for 6-8 cycles at 21-day intervals.
Cochrane Database Syst Rev
December 2024
Medical Oncology, The Kinghorn Cancer Care Centre, St Vincent's Hospital, Sydney, Australia.
Radiat Oncol
December 2024
Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Background/aim: Current approaches for locally advanced rectal cancer (LARC) typically recommend neoadjuvant chemoradiotherapy (nCRT) with 5-fluorouracil (5FU) or its oral analogs followed by surgery as the standard of care. However, the question of whether intensifying concurrent chemotherapy by adding oxaliplatin to the 5FU-based backbone can yield better outcomes remains unresolved. This study aimed to investigate the benefits of incorporating oxaliplatin into fluoropyrimidine-based chemoradiotherapy (CRT) to increase locoregional control and survival.
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