Rationale: data about the role of prolactin (PRL) in breast cancer patients are controversial. This hormone might potentially play an important role in breast cancer initiation and development in rodents, as well as, at least partly, in humans. The aim of this study was to investigate the possible relationship between circulating levels of PRL and parameters of primary tumor in breast cancer patients. The main experimental group consisted of 46 female patients with histologically confirmed diagnosis of breast cancer. There were two control groups: apparently clinically healthy women (40), and female patients with other types and locations of cancer (33). Baseline levels of PRL were determined both in the main and in control groups. Parameters of primary tumor (histological diagnosis, degree of differentiation, location, and size) have been determined. Results were processed by means of nonparametric tests. The circulating levels of PRL before treatment were significantly higher in breast cancer patients in comparison to controls. The average size of the primary tumor in breast cancer patients with hyperprolactinemia before treatment was significantly higher (U=125.5, p<0.01) than in those with normoprolactinemia. The calculated correlation coefficient between PRL and the size of primary tumor in hyperprolactinemic breast cancer patients was statistically significant (r=0.68, p<0.0001). In normoprolactinemic, and in patients with other locations of cancer such a correlation did not exist. Serum levels of PRL are, probably, directly dependable on the size of primary tumor in breast cancer patients, especially in those with hyperprolactinemia, but this is not differentiation dependent phenomenon.

BACKGROUND AND PURPOSE Carcinoembryonic antigen (CEA) is used as a tumour marker in breast cancer (BC). In order to assess diagnostic value of CEA in BC we examined its serum levels and frequencies of its increase in breast cancer patients (BCP), and compared them to those in controls. We also determined CEA in patients with metastatic and non-metastatic BC, and calculated sensitivity and specificity of CEA in BC. PATIENTS AND METHODS The main experimental group consisted of 47 female patients with histologically proved diagnosis of BC. There were two control groups: clinically healthy women, and female patients with other locations of cancer. Circulating levels of CEA were measured by means of immunoradiometric assay. Results were processed by means of t-test and two-way analysis of variance. RESULTS Circulating levels of CEA, before treatment in BCP, were significantly higher (p<0.0001) than in healthy women, and in patients with other cancers (p<0.007), while serum CEA in other cancer patients was significantly higher (p<0.01) than in healthy control. There was a difference between frequencies of CEA increase in BCP and healthy women, while such a difference did not exist between BCP and other cancer patients. The circulating levels of CEA in metastatic BCP were significantly higher (p<0.03) in comparison to non-metastatic patients. Sensitivity and specificity of CEA in BCP was 65.0%, and 57.1%, respectively. CONCLUSIONS CEA does not have high tumour specificity for BC, since its circulating levels as well as frequencies of its increase may be elevated in patients with other types and locations of cancer, different from breast cancer. CEA can be detected in the serum of majority of patients with metastatic BC. CEA may be used as prognostic tumour marker in advanced BC.

Thalidomide was first introduced to the market in Germany under the brand name of Contergan in 1956, as a non-barbiturate hypnotic, advocated to ensure a good nights sleep and to prevent morning sickness in pregnancy. It was advertised for its prompt action, lack of hangover, and apparent safety. It has been banned from the market since 1963 after it caused the worldwide teratogenic disaster: babies exposed to thalidomide in utero during the first 34-50 days of pregnancy were born with severe life-threatening birth defects. Despite its unfortunate history, thalidomide has attracted scientific interest again because of its recently discovered action against inflammatory diseases and cancer. Its broad range of biological activities stems from its ability to moderate cytokine action in cancer and inflammatory diseases. Early studies examined its anxiolytic, mild hypnotic, antiemetic, and adjuvant analgesic properties. Subsequently, thalidomide was found to be highly effective in managing the cutaneous manifestations of leprosy, being superior to Aspirin in controlling leprosy-associated fever. Recent research has shown promising results with thalidomide in patients with myeloma, myelodysplastic syndrome, a variety of infectious diseases, autoimmune diseases, cancer, and progressive body weight loss related to advanced cancer and AIDS. Here we review the history of its development, pharmacokinetics, metabolism, biologic effects, and the results of clinical trials conducted thus far. Further research in this field should be directed towards better understanding of thalidomide metabolism, its mechanism of action, and the development of less toxic and more active analogs.

We describe the development of an immunofluorescent method for the detection of resistance to agents which affect the integrity of the cellular microtubular network. Three pleiotropic resistant MCF-7 human breast carcinoma cell lines mixed with vaginal adenocarcinoma cells were selected in serially increasing drug concentrations, and demonstrated a 30-fold increase in resistance to colchicine. Transport studies indicated that there was no difference in drug accumulation between the sensitive and resistant lines. The colchicine-binding capacity of cell extracts from sensitive and resistant cells was similar (Kd for sensitive cells was 1.9 x 10(-6) M and for resistant cells 1.58 x 10(-6) M). There were, however, significant differences in cytoskeletal morphology between sensitive and resistant cells. Drug-sensitive cells were mostly large (about 70 microns 2) and flattened. Their cytoplasm was filled with a microtubular network in which, in most of the cases, single fibers could be differentiated. Cells usually had a microtubule-organizing center and paracortical bundles of microtubules. In contrast, drug-resistant cells were mostly rounded and grew in clumps. In only 40% of these cells could single microtubular fibers be differentiated. Resistant cells lacked a microtubule-organizing center and had no clear paracortical bundles of microtubules. The tubulin-binding agents tested caused a sequence of morphological changes in sensitive cells. These changes included precipitation of tubulin and disappearance of cytoskeletal structure. Changes occurred initially within 3 h of incubation, but were expressed in all cells after 6 h. If, after 3 h of drug exposure, cells were subcultured in drug-free media, the cytoskeletal structure reformed within 10 h. Maximal recovery of cytoskeletal structure occurred 22 h after drug removal and was sustained up to 36 h. In contrast to changes observed in sensitive cells, drug exposure did not induce changes in the morphology of cytoskeleton in resistant cells. Cells from all three resistant lines reverted to sensitivity after 7 months of culture in drug-free media. This was first detected by immunofluorescence and then confirmed by cloning assay. Since the cytoskeletal disintegration of sensitive cells is readily detectable within a few hours of in vitro drug treatment, immunofluorescent imaging may have its clinical application in predicting the sensitivity/resistance to microtubule-binding agents.