Description of a new human breast cancer cell line, IIB-BR-G, established from a primary undifferentiated tumor.

The establishment of a new human breast cancer cell line (IIB-BR-G) was successful after a previous growth of the cells isolated from a breast primary tumor in a female nude mouse. The IIB-BR-G cell line and the primary tumor do not express estrogen or progesterone receptors. Vimentin and keratin expression were found in the cell line and in the nude mouse tumor. This cell line displays high morphological heterogeneity with atypical multinucleated megacells, and it is capable of anchorage-independent growth and tumor formation in nude mice. The cytogenetic analysis confirmed its human origin and revealed multiple marker chromosomes and extensive chromosomal alterations including rearrangements, gains, losses, isochromosomes, and double minutes (DMs).

The expression of progesterone receptors coincides with an arrest of DNA synthesis in human breast cancer.

Two main models to account for the heterogeneous expression of estrogen receptors (ER) and progesterone receptors (PR) in human breast cancer have been proposed: the clonal model and the stem cell model. The authors previously provided evidence supporting the stem cell model since it was found that most of the proliferating cells in ER-positive (ER+) human breast cancer lack ER and that the ER-negative (ER-) and ER+ subpopulations are interrelated. The authors have analyzed in eighteen ER+/PR+ primary breast tumors the simultaneous expression of ER or PR (by immunohistochemistry) and DNA synthesis (by autoradiography) after 30 minutes of 3H-thymidine incorporation. The authors demonstrated that: (1) the average numbers of ER+ and PR+ cells were similar (36.8 +/- 10.7% and 39.3 +/- 17.6%, respectively); (2) The thymidine-labeling indexes of the ER+, ER-, PR+, and PR- subpopulations were 0.53 +/- 0.69%, 0.74 +/- 0.49%, 0.21 +/- 0.21 and 0.94 +/- 0.54%, respectively; and (3) 75.2% of the DNA-synthesizing cells were ER-, and 88.8% of them were PR-. The authors conclude that the cellular subpopulations expressing ER and PR were not identical, and the expression of PR was associated with a lower rate of cellular proliferation than was ER expression.

[Digitalis therapy used according to the "rational" method. Techniques of application and clinical advantages (author's transl)]. / La terapia digitalica attuata con metodo razionale. Tecnica di applicazione e vantaggi clinici.

Digitalis therapy in cardiac failure is used by physicians according to conventional dosages; we call this type of digitalization "empiric". With this method digitalis intoxication in hospitalized patients is likely to occur in 8 to 20% of the cases. Another method of digitalization which we call "rational" is based upon an initial dosage of 0.015 mg per Kilo of digoxin, followed by a maintenance dosage determined by the relationship between initial dosage and daily rate of elimination. The latter depends upon the individual value of endogenous creatinine clearance (determined by age, weight and sex). Blood level of digoxin during steady state was measured in 454 patients divided randomly in four groups, each of whom following a different protocol of digitalization: 31 patients were treated with the rapid "empiric" digitalization (group I), 249 patients with the slow "empiric" digitalization (group II), 81 patients with the "rational" digitalization (group III), and 93 patients after a initial "empiric" dosage were treated with a maintenance dosage calculated by the "rational" method. An excessive initial dosage (blood level of digoxin > 2 ng/ml) was observed in 47.9% of patients of group I, in 15.9% of patients in group II, in 9.8% of patients of group III and in 14.7% of patients of group IV. manifestations of digitalis intoxication occurred in 30% patients of group I, in 10% of patients of group II, in 4.9% of patients of group III, and in 2.1% of group IV. Blood value of digoxin below therapeutic levels (under 0.5 ng/ml) was observed in only 13.1% of patients of group II, in 8.6% of patients of group III, and in 8% of patients of group IV. The lower percentage of digitalis intoxication observed in patients treated with "rational" method of digitalization is highly significant if compared with that observed in patients treated with empiric digitalization. The use of the "Lanoxin-rulex" makes the rational digitalization easier to handle, and gives the physicians the habit of considering the more important determinants of digoxin blood level. Conditions more likely to determine a wrong digitalis dosage are discussed in detail.