Vascular endothelial growth factor receptor-1 expression in breast cancer and its correlation to vascular endothelial growth factor a.

VEGF-A is the most potent angiogenic factor in tumour angiogenesis. Its effects are mediated via two receptors VEGFR-1 and VEGFR-2. Primary aim of our study was to examine the expression of VEGFR-1 in breast cancer and its correlation to VEGF expression, lymph node status, tumour size, histological grade, and hormone receptor status. To examine the VEGFR-1 and VEGF expressions in tumour and surrounding tissue of 51 breast cancer patients, and in healthy breast tissue of 30 benign breast diseases patients, we used three-step immunohistochemical staining. VEGFR-1 and VEGF expressions were significantly increased in breast cancer tumour in relation to surrounding tissue (P < 0.01), and the VEGF expression was significantly increased in lymph node positive breast cancer patients (P < 0.01). VEGFR-1 and VEGF expressions were significantly higher in breast cancer tumour compared with healthy breast tissue (P < 0.01). Significant correlation between VEGF and VEGFR-1 expressions was found (P < 0.05). No significant correlations between VEGF and VEGFR-1 expressions and tumour size, histological grade, and hormone receptor status were found. Increased expression of VEGFR-1 and VEGF in breast cancer tumour and significant correlation between these proteins suggest the possible role of VEGF/VEGFR-1 signalization in breast cancer development, although VEGFR-1 potential prognostic value was not confirmed.

Interleukin 13 expression in the primary breast cancer tumour tissue.

INTRODUCTION: The aim of this study was to investigate the presence and the expression levels of the interleukin 13 (I1-13) in the primary breast cancer tumour tissue in relation to the unchanged breast tissue in the same patients and to the breast tissue in the patients with benign breast disease, and to investigate the correlation between the IL-13 expression levels and the pathohistological factors, and between IL-13 expression and estrogens and progesterone receptor status. MATERIALS AND METHODS: 50 patients with invasive ductal breast cancer and 20 patients with benign breast diseases were included in this prospective case-control study. The three-step immunohistochemical staining was used for testing the levels of IL-13 expression and hormone receptor status. RESULTS: IL-13 was present in breast cancer tumour tissue, and in the surrounding unchanged tissue in the same patients, and in breast tissue in patients with benign breast disease. The expression of IL-13 was significantly higher in breast cancer tumour compared with surrounding tissue (P < 0.05) of the same, lymph node-positive patients. In addition, IL-13 expression was significantly higher in breast cancer tumour compared with breast tissue in patients with benign breast diseases (P < 0.01). There was significant correlation between IL-13 expression and tumour size in patients with lymph node-negative breast cancer (r = 0.405, P = 0.050). There was no significant correlation between IL-13 expression and the other pathohistological factors, and no significant correlation between IL-13 expression and the lymph node status. CONCLUSION: Obtained results suggest possible involvement of IL-13 in breast carcinogenesis.

Interleukin 18 expression in the primary breast cancer tumour tissue.

AIM: To investigate the presence and expression levels of the IL-18 in the primary breast cancer tissue in relation to the unchanged breast tissue in same patients and the breast tissue in patients with benign breast disease, as well as the correlation between the IL-18 expression levels and pathohistological factors, including the correlation between IL-18 expression and the estrogens and progesterone receptor status. METHODS: This prospective randomized study was conducted at the Policlinic for Laboratory Diagnostics of the University Clinical Centre of Tuzla. 50 patients with invasive ductal breast cancer and 20 patients with benign breast diseases were included in the study. The tree-step immunohistochemical staining was used for testing the levels of IL-18 expression and hormone receptor status. RESULTS: IL-18 was present in the breast cancer tumour, in the surrounding unchanged tissue of the same patients and in the breast tissue of patients with benign breast tumour and other benign breast disease. The expression of this interleukin was significantly higher in breast cancer tumour tissue as compared to its expression in surrounding unchanged tissue of the same patients (p < 0.05), whereas IL-18 expression was not significantly higher in breast cancer tumours compared to its expression in breast tissue of the patients with benign breast diseases (p = 0.057). There was no significant correlation between IL-18 expression and the lymph node status, and between IL-18 expression and the pathohistological factors. CONCLUSION: The results suggest possible involvement of IL-18 in complex mechanisms of breast carcinogenesis.

Circulating levels of prolactin in breast cancer patients.

OBJECTIVES: In order to assess diagnostic value of prolactin (PRL) in breast cancer (BC), we examined its serum levels and frequencies of its increase in breast cancer patients (BCP), and compared them to those in two controls. We also determined circulating levels of PRL in localised and advanced BC and calculated sensitivity and specificity of PRL in BC. PATIENTS AND METHODS: The main experimental group consisted of 47 female patients with histologically confirmed diagnosis of BC. The obtained results were compared to those in two control groups: clinically healthy women, and female patients with other types and locations of cancer. Serum levels of PRL were measured by means of radioimmunoassay. Results were processed by means of t-test and two way analysis of variance. RESULTS: The serum levels of PRL before treatment, as well as the frequencies of its increase, were significantly higher in BCP in comparison to controls (p<0.01, 0.02). The average circulating levels of PRL in patients with advanced BC were significantly higher (p<0.0001) in comparison to patients with localised disease. Sensitivity for PRL in BC was 50%, and specificity was 100%. CONCLUSIONS: Increased levels of PRL can be detected in the majority of patients with advanced BC. PRL has high specificity for BC, especially for metastatic BC, which leads to its diagnostic and prognostic importance in this disease.

Importance of serum prolactin determination in metastatic breast cancer patients.

AIM: To correlate prolactin concentrations in the sera of patients with metastatic breast cancer with time interval to appearance of metastases, their location, and size. METHOD: The prospective study included 46 female patients with histologically confirmed diagnosis of breast cancer. The patients were recruited from the Health Center outpatient clinic and University Hospital Center day-care hospital in Banja Luka, Bosnia and Herzegovina, from January to August 1988. The follow up lasted 5 years. Serum concentrations of prolactin were measured in all patients before (baseline levels) and after the therapy at regular time intervals during the observation period. Their prolactin concentrations were compared with prolactin concentrations in 40 healthy women and 33 female patients with other types of cancer, who served as control groups. Time interval to metastases development, their size, and location were determined in breast cancer patients and compared with those in patients with other types of cancer. RESULTS: The baseline serum concentrations of prolactin were higher in breast cancer patients than in healthy women (610 vs 442 mU/L; p=0.04; Mann-Whitney test), and in patients with other locations of cancers (662 vs 481 mU/L, respectively; p=0.02; Mann Whitney test). Metastases developed in all hyperprolactinemic patients, whereas a third of normoprolactinemic were free of metastases. The average time interval before the occurrence of metastases in patients with very high serum concentrations of prolactin was significantly shorter than that in patients with very low prolactin concentrations (54.3 vs 6.1 months; p<0.001; Mann Whitney test). In hyperprolactinemic patients with metastatic breast cancer, there was a significant correlation between the serum concentration of prolactin before treatment and the time to metastases (r= -0,47; p=0.03) and the size of metastases (r=0,64; p=0.001). CONCLUSION: Hyperprolactinemia could be an indicator of disease progression and poor prognosis in patients with metastatic breast cancer.

The relationship between circulating carcinoembryonic antigen (CEA) levels and parameters of primary tumor and metastases in breast cancer patients.

AIM: The Carcinoembryonic antigen (CEA) is used as a tumor marker for breast cancer (BC). In order to better define clinical usefulness of CEA in breast cancer patients (BCP) we determined its baseline pre-treatment levels and correlated them with main parameters of primary tumor and metastases. PATIENTS AND METHODS: The main experimental group consisted of 47 female patients with histologically confirmed diagnosis of BC. The obtained results have been compared with those of two control groups: clinically healthy women, and patients with other types and locations of cancer. In both cancer groups the parameters of primary tumor (size, grade) and metastases (time interval to metastases, location, size) have been determined. Circulating levels of CEA were measured by the means of immunoradiometric assay. Results were processed by means of t-test, two way analysis of variance in F-test, and logistic general linear model with calculations of Pearson's correlation coefficient. RESULTS: Baseline levels of CEA in BCP were significantly higher than in healthy women (p < 0.0001), and in patients with other types and locations of cancer (p < 0.007). There also was significant difference (p < 0.001) between serum CEA in other cancer patients and healthy women. Baseline CEA levels were in significant positive correlation with the size of primary tumor both in all BCP (p < 0.03) and in hyperCEA BCP (p < 0.002), while in other cancer patients such a correlation did not exist. There was no correlation between CEA and degree of differentiation of primary tumor either in BCP or in other cancer patients. The average circulating levels of CEA in metastatic BCP were significantly higher (p < 0.03) in comparison to non-metastatic patients, while in other cancer patients such a difference did not show up. There was significant correlation (p < 0.0001) between circulating CEA and the size of metastases in all BCP and in subgroup of hyperCEA BCP, while in other cancer patients it was not a case. There was no correlation between serum CEA and other two metastatic parameters either in BCP or in other cancer patients. CONCLUSIONS: CEA does not have high tumor specificity for BC since its baseline levels may be elevated in other types of cancer. Circulating levels of CEA in BCP are directly dependable on the size of both primary and metastatic tumor. CEA is a tumor antigen of less differentiated cancer cells. Circulating CEA is a good prognostic marker for patients with metastatic BC.

Diagnostic usefulness of serum carcinoembryonic antigen determinations in breast cancer patients.

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.

[Correlation of body mass index and aminotransferase activity in healthy adolescents]. / Korelacija indeksa tjelesne mase i aktivnosti aminotransferaza u zdravih adolescenata.

The objective of this study to consolidate the correlation between BMI with the values of ALT and AST of the healthy adolescents in age of 18, 19 and 20 years. To the group of 237 examinees of the healthy adolescents is determined BMI, and is measured the activity of ALT and AST. In the sample of the examinees we had 22% examinees had the increased BMI > or = 25. The examinees who had the increased BMI (> or = 25), had the significant increased values ALT, and only mildly increased values AST in relation to the upper referent values. On the basis of the simple linear regression was confirmed the positive correlation between the of body mass indexes and activities ALT i AST.

Alcohol in alcoholic liver disease is a causative factor for development of allergic skin manifestations.

BACKGROUND: We frequently observed allergic skin reactions in patients with documented history of alcoholic liver disease (ALD). To assess the potential association between alcohol-induced liver damage and urticaria a prospective randomized trial investigating immunologic parameters in various stages of alcoholic liver disease was designed. Fifty patients were available for analysis. METHODS: By means of a multivariate discriminant analysis seven out of a number of laboratory and clinical parameters (level of serum proteins, serum globulins, gamma globulins, albumin/globulin ratio, and immunoglobulins A, E, and G) have been found important for analysis. They were compared with age, general clinical status, degree of progression of alcoholic liver disease, and frequency of appearance of type I skin reactions. Results were further processed by means of logistic general linear models, Chi-square test, and summarized in a structural equation model. RESULTS: Alcoholic liver disease does not influence IgA, IgG, and A/G Index directly, but it increases levels of IgE. About 13% of variance of IgA, IgG, and A/G Index are affected by group membership only in non-alcoholic liver disease, and 27% of variance of IgE can be explained by alcoholic liver disease. There were striking differences in IgE content between alcoholic liver disease and control groups. Degree of liver disease had a negative impact on A/G Index, and on IgA, and a positive on IgG. About 16% of variance can be explained by degree of liver disease. IgE is not degree related. Alcoholic liver disease as a disease was found as the most important predictor of skin reactivity (p = 0.0046). Of all immunologic parameters investigated IgE followed by A/G Index was found as the most significant predictor of allergic skin reactions. The extent of alcoholic liver disease plays not a role in allergic skin manifestations. Alcoholic nature of liver disease itself is a significant factor causing allergic skin reactions (p = 0.0002), but alcoholism itself as an independent factor contributes to increased incidence of skin allergies. CONCLUSIONS: Alcoholic liver disease plays an important role in development of type I allergic skin manifestations. This effect has a direct mechanism through alcohol itself, and an indirect through elevation of IgE. Alcohol in liver disease and not liver disease causes immunologic abnormalities and accounts significantly for increased appearance of allergic skin reactions regardless of the extent of underlying liver disease.

Mechanisms of action and potential therapeutic uses of thalidomide.

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.