ABSTRACT
Lobaplatin as a single agent and in combination with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is investigated in in-vitro models of p53-negative triple-negative breast cancers (TNBCs) and compared with a model of oestrogen receptor-positive p53-positive breast cancer. In addition, the induction of programmed cell death by lobaplatin is further explored. By using cell viability assays and western blotting, the cytotoxic effects of lobaplatin alone and in combination with TRAIL are compared with cisplatin in HCC 1806, HCC 1937, and MCF 7 cells. The multicaspase inhibitor z-VAD-fmk and necrostatin, an inhibitor of necroptosis, are used to demonstrate the mechanism of cell death caused by lobaplatin. Lobaplatin displayed antitumour activity in all three cell lines, which increased time dependently. Cotreatment of lobaplatin and TRAIL induced an increase in cytotoxicity by 30-50% in the different cell lines. The pan-caspase inhibitor z-VAD-fmk as well as necrostatin could weaken but not abolish the cytotoxic effect of lobaplatin and cisplatin. Lobaplatin showed substantial cytotoxic effects in two in-vitro models of p53-mutated TNBC. Cotreatment with TRAIL and platinum agents resulted in increased antitumour activity in the TNBC cell lines investigated. Cell death subsequent to treatment with cisplatin and lobaplatin occurred because of apoptosis. However, caspase-independent mechanisms of programmed cell death were also involved. It was also demonstrated that platinum compounds could induce necroptosis, although to a minor extent.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Cyclobutanes/pharmacology , Organoplatinum Compounds/pharmacology , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Survival , Cisplatin/pharmacology , Humans , Tumor Suppressor Protein p53/geneticsABSTRACT
Adnexal torsion is a rare finding during pregnancy. Here we report a patient with bichorial twin pregnancy in the 21st week of gestation with adnexal torsion. She was admitted with acute abdominal pain. Open laparoscopy was performed and the left adnexa was unwinded successfully. The postoperative follow-up was uneventful. Adnexal torsion as differential diagnosis of acute abdomen in pregnancy should be considered seriously to avoid irreversible lesions of the ovary and (salpingo-) oophorectomy.
