Taken together, we show for the first time that a variety of genes (particularly redox genes such as AKR1C2 and AKR1C3) can be temporally and causally correlated with the acquisition of anthracycline resistance in breast tumor cells.

BackgroundCurrent protocols for the treatment of ovarian cancer include combination chemotherapy with a platinating agent and a taxane. However, many patients experience relapse of their cancer and the development of drug resistance is not uncommon, making successful second line therapy difficult to achieve. The objective of this study was to develop and characterize a cell line resistant to both carboplatin and docetaxel (dual drug resistant ovarian cell line) and to compare this cell line to cells resistant to either carboplatin or docetaxel.MethodsThe A2780 epithelial endometrioid ovarian cancer cell line was used to select for isogenic carboplatin, docetaxel and dual drug resistant cell lines. A selection method of gradually increasing drug doses was implemented to avoid clonal selection. Resistance was confirmed using a clonogenic assay. Changes in gene expression associated with the development of drug resistance were determined by microarray analysis. Changes in the expression of selected genes were validated by Quantitative Real-Time Polymerase Chain Reaction (QPCR) and immunoblotting.ResultsThree isogenic cell lines were developed and resistance to each drug or the combination of drugs was confirmed. Development of resistance was accompanied by a reduced growth rate. The microarray and QPCR analyses showed that unique changes in gene expression occurred in the dual drug resistant cell line and that genes known to be involved in resistance could be identified in all cell lines.ConclusionsOvarian tumor cells can acquire resistance to both carboplatin and docetaxel when selected in the presence of both agents. Distinct changes in gene expression occur in the dual resistant cell line indicating that dual resistance is not a simple combination of the changes observed in cell lines exhibiting single agent resistance.

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Acquired diaphragmatic perforation leading to massive hepatic hydrothorax and respiratory failure is a rare complication of microwave ablation (MWA) of hepatocellular carcinoma (HCC). Imaging modalities to detect pleuroperitoneal communication remain poorly described. We report a nuclear imaging technique used to efficiently diagnose and locate diaphragmatic defects. A 57-year-old male with cirrhosis and HCC presented with respiratory distress after undergoing MWA of a HCC lesion. He was admitted to the intensive care unit for noninvasive positive pressure ventilator support. Chest radiography revealed a new large right pleural effusion. Large-volume thoracentesis was consistent with hepatic hydrothorax. The fluid reaccumulated within 24 hours; therefore an acquired diaphragmatic perforation induced by the ablation procedure was suspected. To investigate,  99mTechnetium-labeled albumin was injected into the peritoneal cavity. The tracer accumulated in the right hemi thorax almost immediately. The patient then underwent transjugular intrahepatic portosystemic shunting in efforts to relieve portal hypertension and decrease ascites volume. Unfortunately, the patient deteriorated and expired after few days. Although diaphragmatic defects develop in cirrhotic patients, such small fenestrations do not normally lead to rapid development of life-threatening pleural effusion. MWA procedures can cause large diaphragmatic defects. Immediate detection of this complication is essential for initiating early intervention.

Liver failure is rarely caused by multiple myeloma (MM). We present an unusual case of MM initially presenting as acute liver injury. A 79-year-old man with new-onset fatigue, decreased appetite, and no history of liver disease was found to have evidence of hepatic decompensation. Liver biopsy demonstrated diffuse plasma cell infiltration, and MM was confirmed with bone marrow biopsy. Chemotherapy was initiated, but the patient decompensated and died due to respiratory failure. MM should be considered on the differential for acute decompensated liver disease. Hepatic involvement of MM at presentation is a poor prognostic indicator, and prompt initiation of treatment can be life-saving.