[Myocardial metastasis from renal cell carcinoma treated with sorafenib].

We present a case of myocardial metastasis from renal cell carcinoma (RCC) during the treatment with sorafenib. A 63-year-old male, who had undergone right radical nephrectomy, received interferon-alpha (IFN), interleukin (IL-2) and 5-flurouracil (5-FU) for the treatment of lung and pleural metastases. However, since this metastasis showed progressive disease, we administered sorafenib. Nine months after the introduction of sorafenib, he complained of dyspnea. Chest computed tomography and cardiac ultrasonography revealed a low density mass at the cardiac muscle of the left cardiac ventricle, suggesting myocardial metastasis of RCC. Molecular targeted therapy achieved a longer survival in advanced RCC patients in comparison with the immunotherapy using cytokines. Therefore, in metastasis evaluation, some organs which have been regarded as rare sites should be carefully evaluated.

[Epithelioid angiomyolipoma of the kidney].

A 50-year-old male was referred to our hospital for a left renal mass which was incidentally found during a medical check-up. Abdominal ultrasonography, computed tomography, and magnetic resonance imaging showed a weak enhancement tumor devoid of fat densities at the lower pole of the left kidney. Under the diagnosis of renal cell carcinoma, radical nephrectomy was performed. Histopathological examination revealed large epithelioid cells, and immunohistochemical staining showed strongly positive for HMB-45. The patient was diagnosed with epithelioid angiomyolipoma of the kidney. Epithelioid angiomyolipoma is a rare variant of angiomyolipoma, which is sometimes occurred aggressive clinical behavior. However, our case remains without evidence of recurrence or metastasis after radical nephrectomy, and showed relatively better prognosis than in previous reports.

[A case of emphysematous pyelonephritis successfully treated by endotoxin absorption therapy and transurethral retrograde drainage].

A 73-year-old male, who had undergone hormonal therapy due to stage D2 prostate cancer, complained of fever up and appetite loss. Abdominal computed tomography showed emphysematous pyelonephritis and right ureteral stone. At first, we could not perform any surgical treatment due to disseminated intravascular coagulation and septic shock. After endotoxin absorption therapy, we performed transurethral retrograde drainage, and successfully treated the emphysematous pyelonephritis. Endotoxin absorption therapy should be performed before surgical treatment in cases of emphysematous pyelonephritis with severe general condition.

Alterations in mRNA expression of myelin proteins in the sciatic nerves and brains of streptozotocin-induced diabetic rats.

Diabetic neuropathy is the most common complication of diabetes. We examined the levels and the mRNA expression of myelin proteins in the sciatic nerves and the brains of streptozotocin-induced diabetic rats. The diabetic rats exhibited a decrease in body weight, elevation of the blood glucose level and a decrease in motor nerve conduction velocity at 2 weeks after streptozotocin injection. In the sciatic nerves of diabetic rats, the level of P0 protein and its mRNA expression were markedly reduced at 20 weeks after the injection. In the brains, the levels of proteolipid protein and myelin-associated glycoprotein and their mRNA expression were selectively decreased at 20 weeks after the injection. This affected expression of myelin proteins was found even when no histological abnormalities were detectable. Considering the functional significance of myelin proteins, this impairment of protein expression is possibly involved in the pathogenesis of diabetic neuropathy, including that in brain disorders.

Alpha-eleostearic acid (9Z11E13E-18:3) is quickly converted to conjugated linoleic acid (9Z11E-18:2) in rats.

We previously showed that alpha-eleostearic acid (alpha-ESA; 9Z11E13E-18:3) is converted to conjugated linoleic acid (CLA; 9,11-18:2) in the liver and plasma of rats that were given diets including 1% alpha-ESA for 4 wk. In this study, we investigated this phenomenon in detail. First, the chemical structure of CLA produced by alpha-ESA administration was determined. After alpha-ESA was orally administered to rats, CLA in rat liver was isolated by HPLC. The positional and geometric isomerism was determined using GC-EI/MS and (13)C-NMR, respectively, and the CLA generated in rats after alpha-ESA feeding was confirmed to be 9Z11E-CLA. Next, the concentrations of alpha-ESA and CLA were determined 0, 3, 6, and 24 h after oral administration of alpha-ESA to rats. Moreover, we also investigated whether enteric bacteria are involved in the conversion of alpha-ESA to CLA using germ-free rats. alpha-ESA was orally administered to germ-free and normal rats and alpha-ESA and CLA were detected in the organs of both groups. In addition, to confirm that this reaction was enzyme-mediated, alpha-ESA was reacted with tissue homogenates (liver, kidney, and small intestine mucous) and coenzymes (NADH, NAD(+), NADPH, and NADP(+)), and the enzyme activities were estimated from the amount of CLA produced. CLA was detected when alpha-ESA was reacted with liver, kidney, and small intestine mucous homogenates and a coenzyme (NADPH). These results indicated that alpha-ESA is converted to 9Z11E-CLA in rats by a Delta13-saturation reaction carried out by an NADPH-dependent enzyme.

Tumor growth suppression by alpha-eleostearic acid, a linolenic acid isomer with a conjugated triene system, via lipid peroxidation.

We have previously shown that conjugated linolenic acids (CLnA) prepared by alkaline isomerization have a stronger antitumor effect than conjugated linoleic acids (CLA). In this study we have compared the suppressive effect on tumor growth of alpha-eleostearic acid (alpha-ESA, 9Z11E13E-18:3) with those of the CLA isomers 9Z11E-CLA and 10E12Z-CLA, using nude mice into which DLD-1 human colon cancer cells were transplanted. The results showed that alpha-ESA, which is a CLnA that can be prepared from natural sources in bulk, had a stronger antitumor effect than CLA. DNA fragmentation was enhanced and lipid peroxidation was increased in tumor tissues of the alpha-ESA-fed mice, which suggested that alpha-ESA induced apoptosis via lipid peroxidation. Furthermore, treatment of DLD-1 cells with alpha-ESA, 9Z11E-CLA and 10E12Z-CLA confirmed that alpha-ESA had a stronger antitumor effect than CLA in cultured cell lines. The induction of apoptosis by alpha-ESA was consistent with enhanced DNA fragmentation, increased caspase activity and increased expression of caspase mRNA following alpha-ESA treatment. Addition of alpha-tocopherol, an antioxidant, suppressed oxidative stress and apoptosis, suggesting that these effects were associated with lipid peroxidation.