Doxorubicin in combination with other cytotoxic drugs has clinical advantages. However, doxorubicin-induced cardiotoxicity negatively impacts clinical utility and outcomes. Cardiotoxicity can result from increased oxidative stress or from a local cytochrome P450 mediated increase in 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE). Oleanolic acid (OA) is a natural pentacyclic triterpenoid with free radical scavenging, cardioprotective, and P450-mediated cyclooxygenase-upregulating properties. We investigated co-delivery of liposomal OA and doxorubicin in a HepG2 model of hepatocellular carcinoma (HCC). OA attenuated the cardiotoxicity induced by doxorubicin without compromising its anticancer activity. Apoptosis assays revealed that co-delivery of DOX and OA produced a synergistic anticancer effect. However, the drugs had antagonistic effects on cardiomyocytes. Female BALB/c nude mice treated with OA-and DOX-loaded liposomes (ODLs) exhibited reduced tumor growth, stable body weight, and stable organ indices. Reduced 20-HETE production suggested ODLs had limited cardiotoxicity. No changes in biochemical or histopathological markers were observed in mice treated with ODLs. Tailored co-delivery of OA and DOX may thus be an effective therapeutic strategy for treating HCC.

Aneurysms of the left main coronary arteries are found in 0.1% of angiograms. This case involves an athlete with a left main coronary artery aneurysm, which was combined with chronic total occlusion of the proximal left anterior descending and proximal left circumflex coronary arteries. The extraordinary clinical presentation in this patient may be associated with good coronary collaterals, which may have developed in the patient in response to chronic total occlusion of the coronary artery by the aneurysm, and repeat myocardial hypoxia during high levels of performance as a soccer player. (Heart 2001;85:e1) Keywords: coronary aneurysm; left main coronary disease; intravascular ultrasonography; electron beam computed tomography Left main (LM) coronary artery aneurysm is very rare, occurring in 0.1% of adults undergoing coronary angiography.1 Although some of these cases had associated multivessel coronary artery disease, to the best of our knowledge there has been no previous report of an LM coronary aneurysm associated with chronic total occlusion of the left anterior descending (LAD) and left circumflex (LCx) arteries at the osteum. Such findings in a young soccer player, together with a review of the possible causes, are presented here. Case reportA 31 year old man was admitted to the coronary care unit following a non-Q wave myocardial infarction which had occurred two hours earlier. He had been a soccer player since childhood and had played regularly up until a year ago. He had no risk factors for coronary artery disease and no unusual history. His physical examination was normal. Laboratory examinations, including erythrocyte sedimentation rate, C reactive protein, complete blood count, serologic test for syphilis, rheumatoid factor, antinuclear antibody, antithrombin III, protein C, and protein S, were normal. Echocardiography showed a greatly dilated LM coronary artery and mild hypokinesia at the left ventricular apex. Fluoroscopy and coronary angiography revealed a calcified giant aneurysm of the LM artery with total occlusion of the LAD and LCx arteries at the osteum ( fig 1), with good collaterals from the normal right coronary artery (RCA). Angiographies, including the cerebrovascular and peripheral arteries, were normal. Electron beam computed tomography (EBCT) confirmed the presence of a 3.0 × 1.5 cm lobulated cystic lesion with a calcification rim from the LM to the LAD and LCx coronary arteries (fig 2A). Intravascular ultrasonography (IVUS) revealed a fusiform giant aneurysm of the LM artery ( fig 2B) and a severe intimal thickening at the osteum of the LAD artery with calcification ( fig 2C). The patient underwent coronary artery bypass surgery and was discharged in a good condition. DiscussionAneurysms of the LM coronary artery are rare.1 Most reported cases of LM artery aneurysms were incidentally noticed at coronary angiography for evaluation of myocardial ischaemic symptoms. As our case presented with a small myocardial infarction, considering the regional wall motion abnormality...

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