The role of prolactin in human breast cancer

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

Fluorimetric profiles, flavonoid and polyphenols content of acacia, meadow and honeydew honey samples and their correlation with colour intensity of honey

Introduction: Previous studies have showed that fluorimetric analysis may be used as a simple, rapid, low cost and reliable method for authentication botanical origin of honey. Primary aims of this study were to record fluo-rescence spactra of acacia, meadow and honeydew honey samples and to determine content of flavonoid and pol-yphenoles in relation to colour intensity of honey. Material and methods: Fluorescence spectra of honey samples were recorded. Spectrophotometric analysis was used to determine flavonoid and polyphenols content. The honey color scoring was developed by the authors as the arbitrary system. Results: Acacia honey showed high fluorescence emission intensity after an excitation at 340 nm, 390 nm and 440 nm. Meadow honey showed fluorescence after excitation at 390 nm and 440 nm, while fluorescence, caused by ex-citation at 340 nm, was absent. Honeydew honey showed low intensity of fluorescence at 440 nm excitation while fluorescence was absent at 340 nm and 390 nm excitation, respectively. Statistically significant difference was found for flavonoids and polyphenols levels, between honeydew and acacia honey. Statistically significant differ-ence in polyphenols levels between meadow and acacia honey was found. There was no statistically significant dif-ference of flavonoids and polyphenols between samples of meadow and honeydew honey. Conclusion: Fluorimetric profiles, flavonoid and polyphenols content, together with colour intensity of honey may be useful in authenitication of botanical origin of honey

Serum levels of oxidative stress marker malondialdehyde in breast cancer patients in relation to pathohistological factors, estrogen receptors, menopausal status, and age

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

Antioxidant and Cytotoxic Activities of Pulicaria dysenterica Methanol Extracts

Aims: The aims of the study were to analyse the polyphenols of Pulicaria dysenterica (L.) Bernh. methanolic extracts from aerial and underground parts, assessment of antioxidant activity and to evaluate their cytotoxicity on HeLa cells of cervical cancer. Methodology: The total phenolic content (TPC) of extracts was determined by the Folin-Ciocalteu spectrophotometric method. The qualitative and quantitative analysis of individual polyphenolic compounds were performed by the reverse phase HPLC method. The antioxidant capacity was evaluated by both, 2,2-diphenyl1-picrylhydrazyl radical and FRAP assay, while cytotoxicity of the extracts was assessed by MTT assay. Results: TPC of the samples were 127.62±2.22 and 244.12±8.84 mg gallic acid equivalent/g extract. In the extracts chlorogenic acid in amount of 10.06±0.96 and 11.32±0.28 mg/g, flavonoid rutin in amount of 5.68±0.13 mg/g and three caffeic acid derivatives were recorded. Extract from underground parts achieved better antioxidant activity with IC50 value 55.36±0.75 µg/mL and FRAP value 2411.12±37.22 µmol Fe2+g-1 compared to the one from aerial parts. Extract from aerial parts achieved better cytotoxic activity with 50% inhibition of viability (IC50) at concentration of 0.389±0.07 mg/mL, against HeLa cells, compared to the extract from underground parts. Conclusion: Analyzed Pulicaria dysenterica extracts contained phenolic acids and flavonoids. The extracts showed good antioxidant activity and cytotoxic properties against HeLa cells in vitro

Comparative study of long-term effects of atorvastatin and rosuvastatin on fasting glucose and hemoglobin A1c in patients with cardiovascular diseases

Introduction: Statins are lipid lowering medications, used for the prevention of cardiovascular diseases (CVD), but have shown to increase the risk of Type 2 diabetes mellitus. The aim of this study was to investigate the effects of high-potency statins, atorvastatin, and rosuvastatin on fasting glucose (FG) and hemoglobin A1c (HbA1c) in CVD patients. Methods: The case–control study included 123 patients from Tuzla Canton, Bosnia, and Herzegovina, with a diagnosis of CVD, treated in three health centers: Public Health Center Gračanica, Banovići, and Čelić. Of total patients, 84 were statin users (39 atorvastatin users and 45 rosuvastatin users) and 39 were not. Demographic data, diagnosis, and data of the therapy were taken from the medical records, as well as data of the FG and HbA1c, measured before or within 3 months of the statin therapy introduction. For the same patients, FG and HbA1c were also measured at least 3 months after the introduction of therapy. Results: Obtained results have shown a significant increase of FG in CVD patients on statin therapy in relation to control (p = 0.034). Comparing the diabetogenic effects of atrovastatin and rosuvastatin, it was found that the HbA1c in patients on atorvastatin therapy was significantly higher comparing to those on rosuvastatain therapy (p = 0.028). The FG was significantly increased (p = 0.027) after atrovastatin therapy. Similar results were obtained in diabetogenic CVD patients, where HbA1c on atorvastatin therapy was significantly higher comparing to HbA1c in those on rosuvastatain therapy (p = 0.039). A significant correlation was found between the increase in FG and HbA1c with the duration of atorvastatin therapy (p = 0.001 and p = 0.033), and between the increase in HbA1c and the duration of rosuvastatin therapy (p = 0.001). Conclusion: Long-term therapy with high-potency statins, atorvastatin, and rosuvastatin, may increase levels of FG and HbA1c in patients with CVD, where atorvastatin shows more significant effects