We studied mechanisms of resistance to the novel taxane cabazitaxel in established cellular models of taxane resistance. We also developed cabazitaxel-resistant variants from MCF-7 breast cancer cells by stepwise selection in drug alone (MCF-7/CTAX) or drug plus the transport inhibitor PSC-833 (MCF-7/CTAX-P). Among multidrug-resistant (MDR) variants, cabazitaxel was relatively less cross-resist...

Insulin resistance is characterized by the diminished ability of insulin to initiate intracellular signaling. It is a common manifestation of obesity and a prelude to type 2 diabetes. The primary targets of insulin are skeletal muscle, adipose, and the liver. Impaired insulin signaling in these tissues reduces glucose uptake and promotes a metabolic syndrome that is characterized by elevated le...

In the last 50 years bacteria have demonstrated a remarkable ability to develop and share resistance to every antibiotic that has been developed, often by quite unexpected mechanisms and much more readily than was originally predicted (Spratt, 1994). Antibiotic resistant bacteria can live and multiply in the presence of therapeutic levels of antibiotics. They can be resistant in their natural s...

Camptothecins are broad-spectrum anticancer drugs that specifically target DNA topoisomerase I. Although the availability of camptothecins has had a significant impact on cancer therapeutics, de novo or acquired clinical resistance to camptothecins is common. Studies of camptothecin resistance using yeast and mammalian cell culture models suggest three general mechanisms of resistance: (1) redu...

The increased use of fluoroquinolones has led to increasing resistance to these antimicrobials, with rates of resistance that vary by both organism and geographic region. Resistance to fluoroquinolones typically arises as a result of alterations in the target enzymes (DNA gyrase and topoisomerase IV) and of changes in drug entry and efflux. Mutations are selected first in the more susceptible t...

The design of cancer chemotherapy has become increasingly sophisticated, yet there is no cancer treatment that is 100% effective against disseminated cancer. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic cell genetic differences in tumors, even those from the same tissue of origin. Frequently resistance is...