Endovascular stent graft treatment of leaking thoracic aortic tuberculous pseudoaneurysm.

Mycobacterium tuberculosis infection is one of the leading causes of death from communicable diseases worldwide. However, the incidence of leaking thoracic aortic tuberculous pseudoaneurysms is rare as a complication. Conventional treatment of a leaking tuberculous pseudoaneurysm involves surgery with graft interposition or patch repair. With the emergence of stent graft treatment as a viable option for leaking pseudoaneurysms, we report a 63-year-old man who had his leaking toracic aortic tuberculous pseudoaneurysm treated with endovascular stent grafting.

Thymidylate synthase as a molecular target for drug discovery using the National Cancer Institute's Anticancer Drug Screen.

Thymidylate synthase (TS) is a critical cellular target for cancer chemotherapeutics, particularly the fluoropyrimidine and antifolate classes of antineoplastic agents. One of the primary mechanisms of clinical insensitivity to these agents is through the overexpression of the target enzyme, TS. Thus, there is a need for the development of agents which selectively target TS-overexpressing malignant cells. To this end, we conducted a search for agents which potentially selectively target TS-overexpressing cells using two separate algorithms for identifying such compounds in the NCI Drug Repository by comparing cytotoxicity profiles of 30000 compounds with the TS expression levels measured by Western blot analysis in 53 cell lines. Using the traditional COMPARE analysis we were unable to identify compounds which maintain a selective ability to kill high TS-expressing cells in a subsequent four cell line validation assay. A new algorithm, termed COMPARE Effect Clusters analysis, enabled the identification of a particular drug cluster which contained compounds that maintained a selective ability to kill TS-overexpressing cell lines in the validation assay. While the identified compounds were selectively cytotoxic to TS-overexpressing cells, we found that they were not specifically targeting TS as a mechanism of action. Apparently, the overexpression of TS was providing a marker for sensitivity. This identified class of compounds which appears to be selectively cytotoxic against cells which overexpress TS may be useful for the development of therapeutics for those whose cancers overexpress TS de novo.