Aberrant expression of selenoproteins in the progression of colorectal cancer.

Since damage to DNA and other cellular molecules by reactive oxygen species ranks high as a major culprit in the onset and development of colorectal cancer, the aim of the present study is to clarify the role of antioxidant seleonoproteins including glutathione peroxidase (GPx), thioredoxin reductase (TXR) and selenoprotein P (SePP), and the effect of oxidative stress on the progression of colorectal cancer. Expression of 14 oxidative stress-related molecules in both tumorous and non-tumorous tissues in 41 patients was examined by immunohistochemistry and Western blot analysis. Expression levels of proteins modified by 4-hydroxy-2-nonenal (4-HNE), malonyldialdehyde (MDA) and 4-hydroxy-2-hexenal (4-HHE), and the positive rate of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in tumorous tissues were much higher than those in non-tumorous tissues. Glutathione (GSH) content in tumor tissues was much lower than that in non-tumorous tissues. Expression level of selenoproteins such as GPx-1, GPx-3, and SePP, which are rapidly degraded during selenium deprivation, was significantly decreased in tumorous tissues, whereas that of GPx-2, which is resistant to selenium deprivation, was increased. Expression of SePP was decreased at stage III and IV, compared to that of stage II. These data suggest that contrasting expression pattern of the antioxidant selenoproteins plays an important role in the progression of colorectal cancer.

[Successful combination therapy with 5'-DFUR and MPA for breast cancer with spinal and vertebral metastases].

We report a case of breast cancer with spinal and vertebral lesions. A 49-year-old premenopausal woman with a left breast tumor was admitted to our hospital for acute weakness of the lower limbs and dysuria. She could neither stand nor walk. The tumor in the left breast was 5.0 cm in diameter with skin ulcer, and it was diagnosed as breast cancer. Magnetic resonance (MR) image showed multiple vertebral and spinal metastases from breast cancer. Chemotherapy, consisting of cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) was initiated. Her symptoms dramatically changed for the better. She became able to walk and urinate. We performed palliative mastectomy after 3 cycles of CAF therapy. Histopathological findings of breast tumor showed scirrhous carcinoma. Although the estrogen and progesterone receptor status of primary tumor was negative, chemo-endocrine therapy, consisting of medroxyprogesterone acetate (MPA) and doxifluridine (5'-DFUR) was given as daily therapy, and vertebral and spinal lesions were reduced. Her condition has remained stable for 4 years. For patients with metastatic breast cancer, complete remission is uncommon, and disease stabilization is a reasonable goal of successful therapy. In this respect, therapy with CAF, followed by MPA and 5'-DFUR, was successful in the patient.

Increase in serum 7S domain of type IV collagen and N-terminal propeptide of type III procollagen levels with normal serum transaminase levels after long-term oral administration of Tegaful-Uracil.

To evaluate whether oral administration of Tegaful-Uracil (UFT(R)), a biochemical modulator of 5-fluorouracil that contains tegafur and uracil, can induce hepatic fibrosis, serum 7S domain of type IV collagen and N-terminal propeptide of type III procollagen levels were measured in 63 UFT(R)-treated, 38 tegafur-treated and 40 untreated patients. Serum transaminase and bilirubin levels were normal in almost all patients. Serum levels of 7S collagen and type III propeptide increased in 25 and 17% of the UFT(R)-treated patients, respectively, although a majority of tegafur-treated and untreated patients showed no increase in these markers. The patients with the elevated levels demonstrated mild or moderate hepatic fibrosis without necroinflammation in the liver. Both serum levels decreased markedly after the discontinuation of UFT(R). These findings suggest that long-term oral administration of UFT(R) can induce hepatic fibrosis without the elevation of serum transaminase levels and necroinflammation in the liver, and serum 7S collagen and type III procollagen are of diagnostic value for UFT(R)-induced hepatotoxicity.