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.     

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.     

The anterior choroidal artery syndrome

We reviewed 12 cases of infarcts in the territory of the anterior choroidal artery (AChA) on CT and/or MRI. In each case vascular occlusion in the region was verified angiographically. Although the extent of the lesion on CT/MR images was variable, all were located on the axial images within an arcuate zone between the striatium anterolaterally and the thalamus posteromedially. The distribution of the lesions on mutiplanar MRI conformed well to the territory of the AChA demonstrated microangiographically. The variability of the extent of the infarcts may be explained by variations in the degree of occlusive changes in the AChA or the development of collateral circulation through anastomoses between the AChA and the posterior communicating and posterior cerebral arteries. The extent of the lesion appeared to be closely related to the degree of neurological deficit.     

Cyclic AMP-dependent phosphorylation of the rat brain ryanodine receptor.

Phosphorylation of the rat brain ryanodine receptor was studied using a monoclonal antibody, Ry-1, against the cardiac ryanodine receptor. A large polypeptide with the same SDS-PAGE mobility as that of the canine cardiac receptor was detected in rat brain membranes by immunoblotting. The brain ryanodine receptor was solubilized from the microsomal membranes with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS), and more than 85% of the solubilized receptor was immunoprecipitated by Ry-1. Immunoprecipitated receptors were phosphorylated by cAMP-dependent protein kinase. The ryanodine receptor was also expressed in cultured fetal rat brain neurons and was phosphorylated by treating the cells with dibutyryl cAMP. The number of cells showing a caffeine-induced Ca2+ transient was increased significantly in the phosphorylating condition. These results suggest that the Ca channel activity of the brain ryanodine receptor is regulated by cAMP-dependent phosphorylation.