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Comparative preclinical activity of the folate-targeted Vinca alkaloid conjugates EC140 and EC145 总被引:1,自引:0,他引:1
Leamon CP Reddy JA Vlahov IR Westrick E Parker N Nicoson JS Vetzel M 《International journal of cancer. Journal international du cancer》2007,121(7):1585-1592
EC140 is a water soluble folate conjugate of desacetylvinblastine monohydrazide (DAVLBH), which is constructed with an endosome-cleavable acyl hydrazone bond. This agent has proven to be active and specific against well established, subcutaneous folate receptor (FR)-positive tumors in multiple animal models. Recent structure-activity and optimization studies have yielded a disulfide bond-containing counterpart to EC140, herein referred to as EC145. This new conjugate was found to retain high affinity for FR-positive cells, and it produced specific, dose-responsive activity in vitro. Comparative in vivo efficacy tests confirmed that, like EC140, EC145 displays activity against both syngeneic and xenograft tumor models. However, EC145 was found to be more active and better tolerated than EC140; hence, more durable complete responses were consistently observed in EC145-treated tumor-bearing animals. Furthermore, EC145 was not found to be active against a FR-negative tumor model. Additional preclinical studies are therefore warranted to better understand EC145's breadth of activity against FR-positive tumors. 相似文献
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Rini BI Tamaskar I Shaheen P Salas R Garcia J Wood L Reddy S Dreicer R Bukowski RM 《Journal of the National Cancer Institute》2007,99(1):81-83
Sunitinib is an inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors, and it has antitumor activity in metastatic renal cell carcinoma and gastrointestinal stromal tumors. To further investigate the fatigue associated with sunitinib therapy, thyroid function tests were performed on patients with metastatic renal cell carcinoma who were receiving sunitinib. Seventy-three patients with metastatic renal cell carcinoma were treated with sunitinib at the Cleveland Clinic Taussig Cancer Center, and 66 of them had thyroid function test results available. Fifty-six (85%) of the 66 patients had one or more abnormality in their thyroid function test results, consistent with hypothyroidism, and 47 (84%) of the 56 patients with abnormal thyroid function tests had signs and/or symptoms possibly related to hypothyroidism. Thyroid hormone replacement was undertaken in 17 patients, and symptoms improved in nine of them. Thyroid function test abnormalities appear to be common in patients with metastatic renal cell carcinoma treated with sunitinib, and routine monitoring is warranted. 相似文献
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The authors present an unusual case of multiple large atrial thrombi attached to permanent pacemaker leads identified by transesophageal echocardiography. Pathogenesis, clinical implications, and therapeutic options of pacemaker thrombi are discussed. 相似文献
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