Epirubicin is equivalent to adriamycin in vitro against many cancer cells but more effective against gastric cancer cells.

We compared the cytotoxic effects of two anthracycline derivatives, epirubicin (EPI) and adriamycin (ADM), against human tumor cells in vitro. Various tumor specimens, obtained at surgery, included 57 liver, 19 lung, 16 gastric, 10 colorectal and 7 breast cancer specimens. These tumor cells were exposed to the same concentration of EPI or ADM for 3 days. The chemosensitivity of each tumor cell type to each drug was then assayed using the in vitro succinate dehydrogenase inhibition (SDI) test. Sensitivity to the treatment was defined as a 50% or greater reduction in the succinate dehydrogenase (SD) activity of the tumor cells, relative to that of the control (untreated) cells. Each cell type, except for gastric cancer cells, was equally sensitive to EPI and ADM. Gastric cancer cells were more sensitive to EPI than to ADM (P less than 0.05). The rate of coincidence, the sum of the co-sensitive and co-resistant rates of all the tumors, was quite high (90.8%). Thus, these findings indicate that EPI and ADM are equally cytotoxic to each tumor cell type, but EPI is more cytotoxic than ADM to gastric cancer cells. Since EPI is reported to be less cardiotoxic than ADM, EPI may replace ADM in cancer chemotherapy.     

Effects of caffeine, nicotine, ethanol and sodium selenite on pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine.

The modulating effects of caffeine, nicotine, ethanol and sodium selenite on development of N-nitrosobis(2-oxopropyl)-amine (BOP)-initiated pancreatic tumors were investigated. Female Syrian golden hamsters were given s.c. injections of BOP (10 mg/kg body weight) or saline alone once a week for 3 weeks and then administered 2000 p.p.m. caffeine, 25 p.p.m. nicotine, 20% ethanol or 4 p.p.m. sodium selenite in their drinking water for the next 37 weeks. Control animals were given tap water alone after BOP initiation. Only the BOP-treated groups developed pancreatic adenocarcinomas and dysplasias. The multiplicity of pancreatic carcinomas was significantly higher (P less than 0.05) in animals receiving caffeine than in the controls. In addition, caffeine treatment slightly increased the incidence of carcinomas. Nicotine and ethanol also showed tendencies to enhance pancreatic carcinogenesis, although there were statistically no significant differences regarding lesion development. In contrast, sodium selenite administration was associated with a tendency for a decrease in the number of carcinomas and dysplasias. Thus, among these chemicals of obvious significance to human life-style, caffeine enhanced the development of pancreatic tumors when administered during the post-initiation phase in this hamster model.     

Immunohistochemical and biochemical identification of pepsinogen isozymes in the hamster lungs: induction by polychlorinated biphenyls.

Pepsinogens are acid protease enzymes of pepsin usually found in gastric mucosa. In the present study, we demonstrated the presence of pepsinogen isozymes in male Syrian golden hamster lung tissues by a combined immunohistochemical and biochemical approach. Immunohistochemically, using rat pepsinogen 1 antibody, pepsinogen positive cells were observed mainly in the epithelia of the terminal bronchioles. They demonstrated morphological features of Clara cells. The pepsinogen isozyme pattern of lung tissue determined by polyacrylamide gel electrophoresis was similar to that of stomach mucosa. Treatment of hamsters with polychlorinated biphenyls at a dose of 500 mg/kg body weight ip caused a 2.8-fold increase in pepsinogen content (p less than 0.01) as well as increase in numbers of pepsinogen positive cells in the lung.     

Pharmacokinetics of fluorinated 2-nitroimidazole hypoxic cell radiosensitizers in murine peripheral nervous tissue.

We have previously reported that KU-2285, a 2-nitroimidazole with a fluorinated N1-substituent (-CH2-CF2CONH(CH2)nOH, n = 2), was a promising hypoxic cell radiosensitizer. In this study the pharmacokinetics of KU-2285 and its related compounds (n = 3 and n = 4) were compared with those of etanidazole (a 2-nitroimidazole with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related compounds (n = 3 and n = 4) to assess the effects of incorporation of a CF2 group. The lipophilicity of the fluorinated compounds was higher than that of etanidazole, as measured by the octanol/water partition coefficient. As the number of CH2 groups increased, the lipophilicity of the compounds in both the KU-2285 and etanidazole series increased. The brain tissue levels of the fluorinated compounds were as low as those of the etanidazole derivatives, while the biological half-lives of the fluorinated compounds in peripheral nervous tissues were shorter than those of related non-fluorinated compounds.     

Surgical treatment of aortic arch aneurysm associated with the aberrant right subclavian artery

A 64-year-old man, who had an aneurysm of aortic arch associated with the aberrant right subclavian artery, was treated successfully. He was pointed out to have an aneurysm of aortic arch three years ago. Three years later angiograms and computed tomography revealed that it became larger compared with the initial finding. He underwent a replacement of the aortic arch using a woven Dacron graft under open distal method. Aberrant subclavian artery was not involved in the aneurysm. But because the left subclavian artery was involved in it, a woven Dacron graft was interposed between the ascending aorta and left subclavian artery. Postoperative course was uneventful and there were no complications.     

Combination therapy with cyclosporin A and steroid in severe case of Vogt-Koyanagi-Harada's disease

A severe case of Vogt-Koyanagi-Haradi's disease was treated with a combination therapy of cyclosporin A and steroid. The therapy was successful and showed no side effects.     

Effects of activin A on anterior pituitary cells fractionated by centrifugal elutriation.

We have shown previously that activin A increases the number of immunoreactive follicle-stimulating hormone (FSH) cells. To further investigate the action of activin A, we examined its effects on anterior pituitary cells fractionated by centrifugal elutriation. Before activin A treatment, FSH cells were widely distributed among various fractions; a higher proportion of FSH cells was found in larger cell fractions (fractions 5-9), and a lower proportion in smaller cell fractions (fractions 2-4). After culture of the cells in each fraction with activin A (10 ng/ml) for 72 h, the number of FSH cells in fraction 4 only was significantly (P less than 0.05) higher by 225% than that in cells cultured without activin A. The amount of FSH secreted into the medium was minimal or undetectable in fractions 1-4. However, FSH secretion tended to be, or was significantly (P less than 0.01 in fraction 9), stimulated by activin A in fractions 5-9, in which the numbers of FSH cells were not significantly affected. These results suggest a dual mode of action of activin A on FSH: activin A increases the number of FSH cells in a specific type(s) of middle-sized cell fraction, and stimulates FSH secretion at least from larger cells without affecting the number of FSH cells.