BACKGROUND Preoperative chemotherapy for hepatic resection of colorectal liver metastases is associated with the development of chemotherapy-associated steatohepatitis (CASH). This increases the risk of perioperative morbidity and mortality. To the authors' knowledge, an animal model for CASH has not been described previously. It has been established that fatty acid bile acid conjugates (FABACs...

The molecular and cellular mechanisms of enhanced toxic effects in tumor cells of the Pt(IV) derivatives of antitumor oxaliplatin containing axial dichloroacetate (DCA) ligands were investigated. DCA ligands were chosen because DCA has shown great potential as an apoptosis sensitizer and anticancer agent reverting the Wartburg effect. In addition, DCA reverses mitochondrial changes in a wide ra...

Oxaliplatin-based chemotherapy is widely used to treat advanced cancer. Oxaliplatin-induced hyperammonemic encephalopathy is rarely reported. Here, we report a case of oxaliplatin-induced hyperammonemic encephalopathy occurring after gemcitabine plus oxaliplatin (GEMOX) chemotherapy in a patient with pancreatic cancer. A 76-year-old man received GEMOX regimen as first-line treatment for pancrea...

BACKGROUND Peripheral neuropathy is one of the most important limitations of oxaliplatin base regimen, which is the standard for the treatment of colorectal cancer. Evidence has shown that Vitamin E may be protective in chemotherapy-induced peripheral neuropathy. The aim of this study is to evaluate the effect of Vitamin E administration on prevention of oxaliplatin-induced peripheral neuropath...

BACKGROUND A major problem in cancer chemotherapy is the existence of primary resistance and/or the acquisition of secondary resistance. Many cellular defects contribute to chemoresistance, but epigenetic changes can also be a cause. METHODS A DNA methylation microarray was used to identify epigenetic differences in oxaliplatin-sensitive and -resistant colorectal cancer cells. The candidate g...

BACKGROUND MSH3 is a DNA mismatch repair (MMR) gene that undergoes frequent somatic mutation in colorectal cancers (CRCs) with MMR deficiency. MSH3, together with MSH2, forms the MutSβ heteroduplex that interacts with interstrand cross-links induced by drugs such as cisplatin. To date, the impact of MSH3 on chemosensitivity is unknown. METHODS We utilized isogenic HCT116 (MLH1-/MSH3-) cells w...

The objective was to relate the gene expression profiles of colorectal cancer cells in culture to the in vitro cytotoxicity of cisplatin and oxaliplatin. We studied the gene expression profiles of six human colorectal cancer cell lines, using the Atlas Plastic Human 8K Microarray from Clontech, and related it to the in vitro cytotoxicities of oxaliplatin and cisplatin obtained by inhibition of ...

We have examined the role of the human organic cation transporters [hOCTs and human novel organic cation transporter (hOCTN); SLC22A1-5] and apical multidrug and toxin extrusion (hMATE) in the cellular accumulation and cytotoxicity of platinum agents using the human embryonic kidney (HEK) 293 cells transiently transfected with the transporter cDNAs. Both the cytotoxicity and accumulation of cis...

Oxaliplatin and fludarabine have different but potentially complementary mechanisms of action. Previous studies have shown that DNA repair is a major target for fludarabine. We postulate that potentiation of oxaliplatin toxicity by fludarabine may be due to the inhibition by fludarabine of the activity of the DNA excision repair pathways activated by oxaliplatin adducts. To test this, we invest...

Acute peripheral neuropathy is dose limiting toxicity of oxaliplatin, a wildly used chemotherapeutic drug in colorectal cancer. The present study aimed to identify the relationship between pretreatment serum magnesium concentration and the acute oxaliplatin-induced peripheral neuropathy. We enlisted 318 colorectal cancer patients who received adjuvant or first-line oxaliplatin-based chemotherap...