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Introduction: The aim of this study was to determine the serum levels of malondialdehyde (MDA) in patients with invasive breast cancer in relation to its serum levels in patients with benign breast disease, and to investigate correlation between MDA serum levels with pathohistological prognostic factors (tumor size, lymph node involvement, and histologic grade [HG]), estrogen receptor (ER) status, and with breast cancer patient’s age and menopausal status. Methods: A total of 43 with well-documented invasive breast cancer were included in this study: 27 with positive axillary’s lymph nodes, and 16 with negative axillary’s lymph nodes, and 39 patients with findings of benign breast diseases. MDA determination in serum of breast cancer and benign breast disease patients was performed by the fluorimetric method, immunohistochemical staining was performed for ER, and routine pathohistological examination was conducted for pathohistological factors. Results: MDA serum levels in breast cancer patients were significantly higher than MDA serum levels in benign breast disease patients (p = 0.042). No statistically significant difference between MDA serum levels in breast cancer patients with and without lymph node metastases was found (p = 0.238). No statistically significant correlations between MDA serum levels and tumor size (p = 0.256), HG (p = 0.124), or number of positive lymph nodes (0.113) were found. A statistically significant correlation between serum MDA levels and ages of breast cancer patients with lymph node metastases was found (p = 0.006). Conclusion: Obtained results support the importance of MDA in the carcinogenesis of breast cancer. According to our findings, serum level of MDA could not be a useful prognostic factor in breast cancer.

The study was designed to determine pre-, intra-and postoperative serum cortisol and prolactin (PRL) concentrations in patients subjected to low abdominal surgery under total intravenous anesthesia (TIVA) with propofol-fentanyl, and under general balanced anesthesia with isoflurane-fentanyl. The prospective study included 50 patients of both sexes, aged between 35 and 60 years, subjected to elective low abdominal surgery. Patients were randomly divided into two groups: an experimental group, consisting of 25 ASA I/II (American Society of Anesthesiologists I/II classification) patients treated under TIVA with propofol-fentanyl, and a control group consisting of 25 ASA I/II patients treated under balanced anesthesia with isoflurane-fentanyl. The length of the surgery and the degree of the surgical trauma did not differ significantly between the two anesthesia groups. Blood samples for cortisol and PRL measurements were drawn at exact time points: 30 minutes before the beginning of the surgery (T0), 30 minutes after the beginning of the surgery (T1), at the end of the surgery (T2), 2 hours after the surgery (T3), and 24 hours after the surgery (T4). Serum levels of cortisol and PRL were measured using commercially available kits. The results were evaluated with the nonparametric Mann-Whitney test. The serum concentration of cortisol measured at T1 time point in patients treated under TIVA was significantly lower (p=0.04) than that in patients treated under general balanced anesthesia. The average circulating levels of PRL measured at T1, T2 and T3 time points in patients treated under TIVA were significantly lower (p=0.003; p=0.002; p

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.

Introduction: The aim of this study was to investigate the presence and the expression levels of the interleukin 13 (IL-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 immunohistoc-hemical 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 brea-st cancer tumour compared with breast tissue in patients with benign breast diseases (P < 0.01). The-re 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.

Mnogi su objavljeni podaci o raku dojke i prolaktinu (PRL) proturječni. PRL je prvo bio prepoznat kao hormon koji ima važnu ulogu u inicijaciji i napredovanju raka dojke kod glodavaca i barem djelomično kod ljudi. Ljudske stanice raka dojke u kulturi sintetiziraju biološki aktivni PRL te on djeluje u autokrinoj/ parakrinoj stimulacijskoj petlji (engl. autocrine/paracrine stimulatory loop) unutar tkiva dojke. Aktivnošću tog liganda posreduje izooblik prolaktinskog receptora (receptor prolaktina, PRLR) koji se nalazi na epitelu, odnosno kojeg luči epitel dojke kod ljudi. Kompleks PRL/PRLR se povezuje te aktivira nekoliko signalnih putova koje dijeli s drugim članovima nadskupine receptora citokina. Prijenos signala PRLR započinje s tri tirozin-kinaze, odnosno Jak2, Src i Tec. U nedavno objavljenim podacima upućuje se na funkcionalnu ulogu PRL unutar jezgre gdje on djeluje zajedno s cikloBlinom B kao pobuđivačem transkripcije. Nekoliko epidemioloških istraživanja ukazalo je na moguću funkciju PRL kao čimbenika napredovanja raka dojke kod ljudi. PRL bi mogao biti važan lokalni promotor rasta uključen u patogenezu raka dojke kod žena. Hiperprolaktinemija bi mogla biti pokazateljem napredovanja bolesti i nepovoljne prognoze. U kliničke pristupe kontroliranju bolesti trebalo bi uključiti antagoniste interakcije PRL/PRLR ili signalnu transdukciju povezanu s recep-torom PRL., Much of the literature on human breast cancer and prolactin (PRL) appears to be contradictory. PRL has been Brst recognized as a hormone that plays an important role in breast cancer initiation and development in rodents, and, at least partly, in humans. Bioactive PRL is synthesized by human breast cancer cells in culture and acts in an autocrine/paracrine stimulatory loop within breast tissue. The actions of this ligand are mediated by PRL receptor (PRLR) isoforms found on, or secreted by, human breast epithelium. The PRL/PRLR complex associates with, and activates, several signaling pathways that are shared with other members of the cytokine receptor superfamily. Proximal PRLR signaling is initiated by three tyrosine kinases, namely Jak2, Src, and Tec. Some recent literature data have indicated a functional role for PRL within the nucleus where it acts in a complex with cyclophilin B as a transcrip-tional inducer. Several epidemiological studies have indicated that PRL may also function as a progression factor for human breast cancer. PRL might be an important local growth promoter involved in the pathogenesis of human breast cancer. Hyperprolactinemia could be an indicator of disease progression and poor prognosis and clinical approaches to controlling this disease need to incorporate antagonists of PRL/PRLR interaction or PRL receptor-associated signal transduction.

Uvod: Cilj studije bio je utvrditi prije-, intra- i poslijeoperacijske koncentracije glukoze i laktata u serumu bolesnika podvrgnutih operacijskom zahvatu u donjem dijelu trbuha pod totalnom intravenskom anestezijom (TIVA) propo-folom-fentanilom odnosno općom izbalansiranom anestezijom izofluranom-fentanilom. Materijali i metode: U ovu prospektivnu studiju bilo je uključeno 50 bolesnika obaju spolova, u dobi od 35 do 60 godina, podvrgnutih operaciji donjeg dijela trbuha. Bolesnici su nasumce podijeljeni u dvije skupine: eksperimentalnu skupinu od 25 bolesnika s ASA I/II (klasifikacija Američkog udruženja anesteziologa) operiranih pod TIVA i kontrolnu skupinu od 25 bolesnika s ASA I/II operiranih pod izbalansiranom anestezijom. Dvije skupine nisu se značajno razlikovale prema duljini operacije i stupnju kirurške traume. Uzorci krvi za mjerenje glukoze i laktata uzimali su se u točno određenim vremenskim točkama: 30 minuta prije početka operacije (T0), 30 minuta od početka operacije (T1), na kraju operacije (T2), 2 sata nakon završetka operacije (T3) i 24 sata nakon završetka operacije (T4). Serumske koncentracije glukoze i laktata mjerile su se pomoću testova dostupnih na tržištu. Rezultati su se analizirali pomoću Mann-Whitneyevog testa. Rezultati: Serumske koncentracije glukoze izmjerene u vremenskim točkama T1, T2 i T3 bile su značajno niže (P = 0,03, P = 0,001 odnosno P < 0,001) u bolesnika operiranih uz TIVA propofolom-fentanilom nego u onih operiranih uz opću balansiranu anesteziju izofluranom-fentanilom. Srednja koncentracija laktata u krvotoku izmjerena u točki T4 bila je značajno niža (P = 0,001) kod bolesnika operiranih uz TIVA nego u bolesnika operiranih uz balansiranu anesteziju, dok je laktat u T1 bio niži u bolesnika operiranih uz balansiranu anesteziju (P = 0,01). U skupini bolesnika operiranih uz balansiranu anesteziju srednje serumske koncentracije glukoze i laktata izmjerene u T1,T2 i T3 bile su značajno više od njihovih bazalnih koncentracija (P < 0,001). Koncentracije glukoze izmjerene u T2 i T3 bile su iznad gornje granice normalnog raspona. U bolesnika na TIVA srednje serumske koncentracije glukoze izmjerene u T1, T2, T3 i T4 bile su značajno više (P < 0,001 odnosno P = 0,001) od njihovih ba-zalnih vrijednosti, ali su samo one izmjerene u T2 prelazile gornju normalnu vrijednost. U ovih bolesnika su koncentracije laktata u serumu izmjerene u T1, T2, T3 i T4 bile značajno više (P < 0,001) od bazalne koncentracije. Zaključak. Dobiveni rezultati ukazuju na to da je metabolični odgovor na kirurški zahvat vjerojatno ublažen odnosno poboljšan u bolesnika operiranih uz TIVA propofolom-fentanilom u usporedbi s onim kod bolesnika operiranih uz opću balansiranu anesteziju izofluranom-fentanilom., Background: To determine pre-, intra- and postoperative serum glucose and lactate concentrations in patients subjected to low abdominal surgery under total intravenous anesthesia (TIVA) with propofol-fentanyl, and in those under general balanced anesthesia with isoflurane-fentanyl. Materials and Methods: This prospective study included 50 patients of both sexes, aged between 35 and 60 years, subjected to low abdominal surgery. Patients were randomly divided into two groups: experimental group of 25 ASA I/II (American Society of Anesthesiologists I/II classification) patients treated under TIVA, and control group of 25 ASA I/II patients treated under balanced anesthesia. The length of surgery and the degree of surgical trauma did not differ significantly between the two anesthesia groups of patients. Blood samples for glucose and lactate measurements were drawn at exact time points: 30 minutes before the beginning of the surgery (T0), 30 minutes after the beginning of the surgery (T1), at the end of the surgery (T2), 2 hours after the surgery (T3), and 24 hours after the surgery (T4). Serum levels of glucose and lactate were measured using commercially available kits. The results were evaluated with nonparametric Mann-Whitney test. Results: Serum concentrations of glucose measured at T1, T2 and T3 time points in patients treated under TIVA with propofol-fentanyl were significantly lower (P = 0.03, P = 0.001 and P < 0.001, respectively) than those in patients treated under general balanced anesthesia with isoflurane-fentanyl. The mean circulating level of lactate measured at T4 point in patients treated under TIVA was significantly lower (P = 0.001) than that in patients treated under balanced anesthesia, while T1 lactate was lower in patients treated under balanced anesthesia (P = 0.01). The mean serum concentrations of glucose and lactate measured at T1, T2, and T3 points were significantly higher related to their baseline levels in patients treated under balanced anesthesia (P < 0.001). Both T2 and T3 values of glucose were above the normal range. The mean serum levels of glucose determined at T1, T2, T3, and T4 in patients under TIVA were significantly higher (P < 0.001; P = 0.001) than the baseline level, however, only the level measured at T2 point exceeded the upper nor-mal value. Serum lactate levels measured at T1, T2, T3, and T4 were significan-tly higher than the baseline level (P < 0.001) in patients under TIVA. Conclusions: The results obtained suggested the metabolic response to sur-gery to be probably attenuated and thus improved in patients treated under TIVA with propofol-fentanyl in comparison with that in patients treated under general balanced anesthesia with isoflurane-fentanyl.

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.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.The serum levels of PRL before treatment, as well as the frequencies of its increase, were significantly higher in BCP in comparison to controls (p0.01, 0.02). The average circulating levels of PRL in patients with advanced BC were significantly higher (p0.0001) in comparison to patients with localised disease. Sensitivity for PRL in BC was 50%, and specificity was 100%.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.

To correlate prolactin concentrations in the sera of patients with metastatic breast cancer with time interval to appearance of metastases, their location, and size.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.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; p0.001; 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).Hyperprolactinemia could be an indicator of disease progression and poor prognosis in patients with metastatic breast cancer.

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.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.Baseline levels of CEA in BCP were significantly higher than in healthy women (p0.0001), and in patients with other types and locations of cancer (p0.007). There also was significant difference (p0.001) 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 (p0.03) and in hyperCEA BCP (p0.002), 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 (p0.03) in comparison to non-metastatic patients, while in other cancer patients such a difference did not show up. There was significant correlation (p0.0001) 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.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.

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 BMIor = 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.

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

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.