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The objective of this study was to examine the role of ion transport mechanisms in clinical anticancer drug resistance. Reduction in intracellular accumulation of cisplatin is believed to be an early change in cisplatin-resistant cells, and may be dependent on the concentration of intracellular chloride (Cl-) ions and intracellular pH. The primary aim of this study was to describe the modifying effects of NHMA (5-N,N hexamethylene; amiloride), a Na+/H+ antiport inhibitor, and/or SITS (4-acetamido-4';isothiocyanostilbene-2,2'-disulfonic acid), a HCO3-/Cl- transport inhibitor, in bicarbonate-containing or bicarbonate-free media on cisplatin (cis-diamminedichloroplatinum(II); CDDP) toxicity between known cisplatin-sensitive (COS31) and cisplatin-resistant (COS31/rCDDP) canine osteosarcoma cells. This study has shown that cell survival can be influenced by the inhibition of the Na(+)-dependent HCO3-/Cl- exchanger using SITS. The addition of SITS increases the intracellular Cl- concentration in canine osteosarcoma cells cultured in a bicarbonate-containing media. In a bicarbonate-free media, the addition of SITS results in a decrease in the cytotoxic action of cisplatin.

Objective: To determine whether serum alpha 1-acid glycoprotein (AGP) concentration was a useful marker of relapse in dogs with lymphoma that were in clinical remission following treatment with doxorubicin., Design: Cohort study., Animals: 12 dogs with lymphoma and 10 healthy dogs., Procedure: Serum AGP concentration was measured in the healthy dogs and in the dogs with lymphoma before treatment, 3 weeks after the first dose of doxorubicin was administered, and every 3 weeks thereafter until relapse (i.e., recurrence of clinically detectable disease such as palpable enlargement of peripheral lymph nodes). Serum AGP concentrations were determined by use of a radial immunodiffusion kit., Results: Mean serum AGP concentration in healthy dogs was significantly less than concentration in dogs with lymphoma prior to treatment. Mean serum AGP concentrations after the first and each subsequent dose of doxorubicin were not significantly different from concentration in healthy dogs. However, mean serum AGP concentrations 3 weeks prior to and at the time of relapse were significantly higher than concentration measured after the first dose of doxorubicin, and were not significantly different from concentration measured before treatment., Clinical Implications: Results suggest that measuring serum AGP concentration may be a useful method of predicting relapse before recurrence of clinically detectable disease in dogs with lymphoma undergoing treatment with doxorubicin.