Cathepsin D-related disease-free interval in pT1 primary breast carcinomas: a pilot study.

In order to address the heterogeneity of the pT1 breast cancer stages, we have been examining the natural and the clinical course of disease in relation to cathepsin D expression, as a molecular marker for the tumor progression that leads to metastasis. The original aim of our pilot study was to determine whether it was possible to distinguish high-risk from low-risk patients, on the basis of nonestrogen- vs. estrogen-regulated cathepsin D expression. Our results showed that estrogen-regulated cathepsin D expression could be useful as surrogate marker of node-positive status. Further, during the natural course of disease, none of 7 pT1N0 patients with tumors bearing nonestrogen-regulated cathepsin D expression developed metastasis. During the clinical course of disease, nonestrogen-regulated cathepsin D expression defined low-risk while estrogen-regulated cathepsin D expression defined high-risk pT1N+ subgroup of patients. Although there is no consensus with respect to metastasis-related prognostic value of cathepsin D expression, our pilot study implies its prognostic value in pT1 breast cancer patients and supports the hypothesis that cathepsin D may promote metastasis in this early stage of disease.

PS2 protein in breast carcinomas: cut-off value of estrogen-regulated expression.

This study includes 152 patients with histologically confirmed breast carcinoma. Steroid hormone receptors (SR), estrogen (ER) and progesteron (PR) receptors, and pS2 protein were assayed on the same cytosolic extract in accordance with the recommendation of EORTC. Our results showed menopausal- and histologic grade-related expression of pS2 protein. Unfavorable carcinoma subgroups, in relation to expression of pS2 protein were defined: postmenopausal carcinomas with histologic grade II, and pre-, as well as postmenopausal carcinomas with histologic grade III. There were overlappings of individual pS2 protein values between favorable and unfavorable carcinoma subgroups in relation to the expression of pS2 protein. Otherwise, no overlapping of pS2 protein values was obtained between ER-positive and ER-negative carcinomas within defined unfavorable menopausal - and histologic grade-related expression of pS2 protein subgroups. The highest pS2 protein level observed in ER-negative unfavorable subgroups (15 ng/mg) was considered as the cut-off value which defined estrogen-regulated expression of pS2 protein.

14C-urea breath test in the detection of Helicobacter pylori infection.

Helicobacter pylori infection is supposed to be one of the major causes of digestive and other diseases. Among a lot of invasive and non-invasive methods for its detection, none is ideal. The aim is an assessment of the Helicobacter pylori infection in the stomach using breath test and comparison to other diagnostic methods, as well as following up the effects of therapy. In 17 patients with digestive discomfort, breath test, rapid urease test and histology were performed, while in 47 patients with proven HP infection the effect of therapy was followed up using breath test and clinical findings. Breath test was performed after per oral administration of the capsule of (14)C urea (37 kBq). Findings of the breath and urease tests were in accordance in 14/17 patients (83%) while breath test and histology in 16/17 patients (94%). During follow-up of the therapeutic effects, breath test and clinical findings were in accordance in 43/47 patients (98%). Breath test can be useful in diagnosis but is a method of choice in following up the patients after therapy for H. pylori infection, because it is non-invasive, fast and precise.

Cathepsin D: association between TN-stage and steroid receptor status of breast carcinoma.

PURPOSE: To assess whether the expression of estrogen-induced protease, cathepsin D, might facilitate biological subgrouping of patients with breast carcinomas, and accordingly, its potential applicability in clinical oncology. PATIENTS AND METHODS: This study includes 70 patients with histologically confirmed breast carcinoma. Pathological findings were classified according to tumor size (T) and the presence or absence of metastases in regional lymph nodes (N). Steroid hormone receptor (SR) density as well as cathepsin D concentrations were assayed in the cytosol of breast carcinomas in accordance with the recommendation of the EORTC. RESULTS AND DISCUSSION: Statistically significant direct correlations were observed between cathepsin D expression and axillary node status as well as SR status. However, it is important to point out that in spite of these statistically significant findings, there were no biologically significant associations due to a wide range of individual cathepsin D values. Baseline levels of cathepsin D expression were found in patients with SR-negative status and node-negative tumors as well as in patients with SR-negative status and tumors of

pS2 in breast carcinoma: association with steroid hormone receptor status.

AIMS AND BACKGROUND: Knowledge of the steroid hormone receptors has proved to be of significant value in breast cancer. In the present study the possible importance of estrogen-regulated pS2 protein was investigated. Our direct purpose was to answer the question whether the expression of pS2 may be a marker of functional heterogeneity with respect to the steroid hormone receptor status. METHODS AND STUDY DESIGN: The study included 152 patients with primary, operable, histologically confirmed breast carcinomas. Histology specimens were reviewed and classified according to type, nodal status, tumor size and grade. Steroid hormone receptors were assayed by biochemical methods according to the procedures recommended by the EORTC. pS2 protein measurement was performed in breast carcinoma cytosols using an immunoradiometric assay. The results were analyzed by non-parametric statistical methods. RESULTS: A statistically significant inverse correlation between pS2 protein expression and histological tumor grade was found. The expression of pS2 protein was confirmed to be correlated with steroid hormone receptor status. However, it is important to point out that in spite of these statistically significant findings there were no significant biological associations due to overlapping individual pS2 protein values. The baseline level of expression of pS2 protein was obtained in histological grade III carcinomas with a negative steroid hormone receptor status. It was shown that the distribution of carcinomas according to the baseline level of pS2 protein expression was heterogeneous among estrogen receptor-positive carcinomas, and strikingly homogeneous among estrogen and progesterone-negative carcinoma. CONCLUSION: Our study suggested that PR and pS2 protein may identify distinct subsets of estrogen receptor-positive breast carcinomas.

[The effect of hemodialysis and continuous ambulatory peritoneal dialysis on renal anemia]. / Utcaj hemodijalize i kontinuisane ambulatorne peritoneumske dijalize na anemiju bubreznih bolesnika.

Anaemia is an almost invariable sign of chronic renal failure [1]. Although many factors have been implicated as causes of this anaemia, it seems probable that deficiency of erythropoietin is the main cause for most patients [2]. Institution of chronic dialysis can improve anaemia in end-stage kidney disease, continuous ambulatory peritoneal dialysis being reported as more successful [3]. The aim of this study was to investigate the influence of haemodialysis and continuous ambulatory peritoneal dialysis on anaemia during the first six months of treatment. We examined 21 persons (14 males and 7 females, aged from 18 to 78 years) on haemodialysis treatment and 13 persons (6 males and 7 females aged from 22 to 64 years) on continuous ambulatory peritoneal dialysis (Table 1). Standard procedures were used for measuring biochemical parameters. Urea and creatinine levels were high, almost incompatible with life, in all tested persons before dialysis treatment. During the first three months of both dialysis techniques urea and creatinine were significantly (p < 0.01) corrected, but remained above the normal ranges (Table 2). Patients on continuous ambulatory peritoneal dialysis have shown significantly (p < 0.01) lower urea and creatinine values compared to patients on haemodialysis (Graph 1). These data suggest better preservation of renal function and better control of the internal environment during continuous ambulatory peritoneal dialysis [6]. All tested patients were severely anaemic before the beginning of dialysis. During the first six months of haemodialysis erythrocyte count, haematocrit and haemoglobin levels were unchanged (Table 3). Transfusions and hepatitis episodes only temporary improved anaemia. Patients on continuous ambulatory peritoneal dialysis exhibited significant correction of anaemia already during the first three months of treatment (Graph 2). Though less significantly, haemoglobin values continued to rise even during the next three months. The reached haemoglobin levels were lower than normal, but significantly higher than values in patients on haemodialysis (p < 0.01), suggesting better control of anaemia during continuous ambulatory peritoneal dialysis. Transfusion requirement was irrelevant, and hepatitis was not noticed, so they cannot be held responsible for the improvement of anaemia. Greater iron consumption, illustrated by higher transferrin saturation, also confirmed increased erythopoitesis in patients undergoing continuous ambulatory peritoneal dialysis. They also had lower blood iron level than those on haemodialysis (who had) numerous blood transfusions. The improvement of anaemia during continuous ambulatory peritoneal dialysis may be the result of reduction in plasma volume [7] as well as an increase in red cell mass and a better clearance of middle molecules in comparison to patients on haemodialysis. The main cause is higher erythropoietin level [8]. All tested patients had low folic acid level. Patients who corrected anaemia showed fall in folat level. This was statistically remarkable during the first three months of continuous ambulatory peritoneal dialysis-from 3.64 ng/ml to 2.09 ng/ml. All these data suggest that both dialysis modalities are effective in the control of protein waste products level, but continuous ambulatory peritoneal dialysis has better influence on the improvement of anaemia that haemodialysis. This can be attributed to better removal of uremic toxins, improved protein metabolism, lower parathyroid hormone level and higher erythropoietin value due to peritoneal macrophage production.