A phase II study of the combination of endocrine treatment and bortezomib in patients with endocrine-resistant metastatic breast cancer.

The majority of patients with hormone receptor-positive metastatic breast cancer die from disease progression despite different types of anti-hormonal treatments. Preclinical studies have indicated that resistance to anti-hormonal therapies may be the result of an activated NF-κB signalling pathway in breast cancer. Bortezomib is a proteasome inhibitor that blocks the NF-κB pathway. Recent pharmacodynamic and pharmaco-kinetic xenograft studies have shown that drug exposure may be a crucial factor for the efficacy of bortezomib in solid tumours. The aim was to investigate whether the addition of bortezomib to anti-hormonal therapy would result in regained antitumour activity in patients with progressive and measurable disease being treated with an endocrine agent. Clinical benefit was defined as patients obtaining stable disease, partial response or complete response after 2 cycles, lasting for at least another five weeks. Bortezomib was administered on days 1, 8, 15 and 22 of a 5-week regimen (1.6 mg/m2). Eight patients received an aromatase inhibitor and bortezomib, while one received tamoxifen and bortezomib. There were 3 grade 3 gastrointestinal toxicities. Median time to treatment failure was 69 days (range, 35-140). Two out of the 9 patients had stable disease for more than 10 weeks. Despite an effective target inhibition, suggested in peripheral blood mononuclear cells and available tumour samples, no objective antitumour responses were observed. Addition of a proteasome inhibitor to anti-hormonal therapy resulted in a clinical benefit rate of 22% in a limited number of patients with endocrine resistant and progressive metastatic breast cancer. The demonstrated proteasome inhibition in tumour tissue provides evidence that the lack of clinical responses is not attributed to deficient drug exposure.

Diagnostica--a Bayesian decision-aid system--applied to hypertension diagnosis.

"Diagnostica" is a Bayesian statistical tool designed to collect and store the patient's data, suggest a diagnosis, and explain the decision in terms of density distributions. The program is written in C language on MacIntosh support. It is described using the case study of differential diagnosis between essential and secondary hypertensions (i.e., fibrodysplastic renal artery stenosis, atheromatous renal artery stenosis, Conn's syndrome, nephropathy and pheochromocytoma). Seventeen experimental parameters were taken into consideration, all of them available during the first medical examination. The density distributions of all items were established from the ARTEMIS experimental database. Both a priori probabilities of different types of hypertension and loss coefficients are taken into account in the calculations. Diagnostica can be used in a "make diagnosis" mode or in an "edition" mode. In the first case it can serve a physician in everyday practice; in the second it becomes a tool for medical research.

[Nutritive value of daily food rations prepared in different regions of the country. III. The levels of calcium, phosphorus, magnesium, iron and potassium]. / Wartosc odzywcza calodziennych racji pokarmowych odtwarzanych w kilku regionach kraju. Cz. III. Zawartosc wapnia, fosforu, magnezu, zelaza i potasu.

Studies on the content of macrominerals in daily diets reconstructed in 1988 on the basis of the analysis of family budgets in 1986 carried out by the Central Statistical Bureau were carried on. Two social groups i.e. manual and mental workers with medium income were considered. The diets were prepared for 5 regions (Warszawa, Lublin, Olsztyn, Poznan, Wroclaw). According to the studies the requirements for calcium and magnesium were met in about 70% and those for iron in about 84%. The content of potassium in the diets was in the range of recommended allowances while the phosphorus exceeded the allowances by about 20-30%. The comparison of the presently studied diets with the ones from 1973, 1980, 1981 showed a lower degree of realization of the recommended intake of calcium and magnesium in 1986. The content of studied minerals in the diets was usually similar in all five regions.