gw2974 and Body-Weight

To determine if endurance exercise training performed prior to administration of the anticancer drugs DOX and GW2974 would be cardioprotective.. Rats remained sedentary or exercise trained for 10 weeks. Following the exercise or sedentary period, rats were randomly assigned to treatment groups. Rats in sedentary and exercise groups received saline or a combination of 10 mg/kg DOX and 30 mg/kg GW2974. Cardiac function was assessed 2, 5, or 10 days following treatments.. Sedentary animals receiving DOX/GW2974 experienced significant cardiac dysfunction. At 2-, 5-, and 10-days post, cardiac function in trained, drug-treated animals was significantly preserved. Additionally, animals exercised prior to DOX/GW2974 injections had significantly lower levels of myocardial lipid peroxidation and caspase-3 and -8 activities compared to their sedentary counterparts.. Exercise training protected against the cardiac dysfunction associated with DOX/GW2974 administration and may be related to an inhibition in apoptotic signaling.

Topics: Animals; Antineoplastic Agents; Apoptosis; Body Weight; Caspase 3; Caspase 8; Doxorubicin; Exercise Therapy; Female; Heart; Heart Ventricles; Lipid Peroxidation; Malondialdehyde; Oxidative Stress; Quinazolines; Rats; Rats, Sprague-Dawley; Ventricular Dysfunction, Left; Ventricular Pressure

Biliary tract cancer (BTC) is the second most common primary hepatobiliary cancer after hepatocellular cancer. At the time of diagnosis, most BTC are at an advanced stage and are unresectable. There is presently no effective curative treatment of the advanced disease nor is there any effective clinical therapy that will prevent the development of BTC. All of these factors render gallbladder cancer nearly incurable with a poor survival rate. The aim of our study was to provide a better understanding of the mechanisms involved in the development of gallbladder carcinoma as the advancement of more effective treatment options would significantly improve prognosis. In the present study, we examined the effect of gefitinib, a selective epidermal growth factor receptor/tyrosine kinase inhibitor (EGFR/TKI), on the development of gallbladder carcinoma in BK5.erbB2 mice. In addition, we examined the effect of another quinazoline derivative, GW2974, which is able to block the activation of both the EGFR and erbB2, in this model. Animals were treated with either 400 ppm gefitinib or 200 ppm GW2974 as a supplement in the diet using either a chemopreventive or therapeutic protocol. The results show that both compounds were potent chemopreventive and therapeutic agents in this mouse model of human BTC. The results also suggest that activation of the EGFR plays an important role in development of BTC in this model and that targeting both the EGFR and erbB2 may be an effective strategy for treatment of this disease.

Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; Blotting, Western; Body Weight; Carcinoma; Cell Line, Tumor; Disease Models, Animal; Enzyme Inhibitors; ErbB Receptors; Gallbladder; Gallbladder Neoplasms; Gefitinib; Humans; In Situ Nick-End Labeling; MAP Kinase Signaling System; Mice; Mice, Transgenic; Microscopy, Fluorescence; Neoplasms, Experimental; Phosphorylation; Protein-Tyrosine Kinases; Quinazolines; Receptor, ErbB-2; Tolonium Chloride