Differences in oestrogen and progesterone receptors, HER-2, p53 expression and proliferation in ductal breast cancers in relation to histopathological grade

In case of breast cancer the grade of differentiation and expression of oestrogen and progesterone receptors falls within the first category of prognostic factors according to the College of American Pathologists. HER-2, p53 and Ki67 belong to the second category and their significance still awaits confirmation. The aim of the present study was to examine the relationship between the intensity of expression of oestrogen receptors (ER), progesterone receptors (PgR), HER-2, p53 and Ki67 in cells of ductal breast cancer of G1, G2 or G3 differentiation grade. In paraffin sections of 60 ductal breast cancers (20 cases in G1, 20 in G2 and 20 in G3), immunocytochemical reactions were performed to detect the expression of ER, PgR, HER-2, p53 and Ki67. Following a semi-quantitative appraisal of the preparations under examination, appropriate statistical tests were used to document significant relationships. We noted significant positive correlations between ER and PgR (the entire group studied, G1–3, and the G1 group), HER-2 and p53 (G2) and between p53 and Ki67 expression (G2). Significant negative correlations were found between ER and p53 (G1–3), PgR and p53 (G1–3, G1, G3) and between PgR and Ki67 (G1–3, G2). The studies performed demonstrated distinct relationships between the expression intensity of various proteins in tumour cells in relation to the grade of differentiation of the tumour. We also showed that a parallel determination of ER, PgR and p53 expression may carry high predictive value as to response to tamoxifen treatment

68. Zastosowanie pamidronianu u chorych z przerzutami raka do kóści

Od pażdziernika 1999 roku oprócz radioterapii zastosowaliśmy leczenie pamidronianem sodowym u 32 chorych z osteolitycznymi przerzutami raka do kości. Przyjęliśmy dawkę 90 mg we wlewie dożylnym co 4 tygodnie, łącznie podano 166 kroplówek. Wiek chorych wahał się od 33 do 81 lat (mediana 62 lata). U 12 pacjentów rozpoznano raka gruczołu krokowego, u 6 – nerki, u 6 – sutka u kolejnych 6 – płuca, u 1 – ślinianki, a u dwóch nie znaieziono punktu wyjścia nowotworu (u jednego pacjenta rozpoznano dwa nowotwory – płuca i gruczołu krokowego). Dwunastu pacjentom podano jeden lub dwa wlewy dożylne pamidronianu i w tej grupie aktualnie nie możemy oceniać wyników leczenia. Dwudziestu chorym podano większą ilość kroplówek (3 – 17). W tej grupie 13 nadal pozostaje w trakcie leczenia, z wycofaniem się bądź znacznym zmniejszeniem dolegliwości bólowych ocenianych według VAS (początkowo 4–8, aktualnie 0–3). Natomiast u 7 przerwano leczenie ze względu na progresję choroby i pogorszenie stanu ogólnego. U kilku chorych wykonane kontrolne zdjęcie radiologiczne kósci wykazały częściowe uwapnienie przerzutu.Obserwowaliśmy niewiele i słabo nasilonych objawów ubocznych leku (6 chorych – objawy grypopodobne, 2 – nudności).Powyższa analiza zachęca do kontynuowania stosowania pamidronianu dwusodowego u chorych z przerzutami do kósci w przebiegu raka o różnej lokalizacji

Loss of estrogen receptor beta expression correlates with shorter overall survival and lack of clinical response to chemotherapy in ovarian cancer patients

Background: Estrogen receptor beta (ERβ) belongs to a large family of nuclear receptors. Recent studies have suggested that ERβ in contrast to ERα might act as a tumour suppressor in ovarian cancer (OVCA). Materials and Methods: Expression of ERβ was detected by immunocytochemistry in 11 OVCA cell lines and by immunohistochemistry in 43 (41 FIGO stage III) OVCA specimens prepared before chemotherapy and 30 specimens from the same group after chemotherapy. Cisplatin sensitivity in the 11 cell lines was also analysed. Results: No significant correlations between cisplatin-sensitivity and expression of ERβ was found in the cell lines. In the cases which responded well to chemotherapy (complete response) ERβ expression at preliminary laparotomy (PL) was significantly higher (p=0.0004) than in those with progressive disease. Kaplan-Meier analysis revealed that the patients with higher ERβ expression (>30% of cells) at PL had an increased overall survival time and progression-free time (p=0.00161 and p=0.03255, respectively) than the patients with lower ERβ espression. Significantly shorter overall survival time characterized the cases with lower immunoreactivity score of ERβ expression at secondary cytoreduction (SCR) (p=0.00346). Conclusion: The loss of ERβ expression in ovarian tumours may be a feature of malignant transformation

Stromal myofibroblasts in breast cancer: relations between their occurrence, tumor grade and expression of some tumour markers

It is suggested that tumour stromal myofibroblasts exert an unfavourable effect on the biology of breast cancer. We are aware of only a single study which examined relationships between manifestation of myofibroblasts in the stroma of breast cancer and clinicopathological data of the patients. The present study was aimed at estimation of the effect exerted by myofibroblasts present in the tumour stroma on principal pathological parameters and on expression of Ki67, P53 and HER-2 proteins in the group of the most frequent breast cancers, the ductal cancers. In paraffin sections of 60 ductal breast cancers (20 cases in G1, 20 in G2 and 20 in G3), immunohistochemical reactions were performed to detect expression of smooth muscle actin (SMA) in order to visualize myofibroblasts, Ki67, P53 and HER-2. The studies demonstrated that the most numerous myofibroblasts were present in G3 cases and they were the least frequent in G1 cases (P = 0.02). Positive correlations were observed between the presence of myofibroblasts in tumour stroma and expression of Ki67 and HER-2 in breast cancer cells in the entire group (P < 0.001 and P = 0.001, respectively), in G2 cases (P = 0.003 and P = 0.03) and in G3 cases (P = 0.01 and P = 0.03). Considering that the higher grade, Ki67 and HER-2 are thought to represent unfavourable prognostic factors, the elevated content of myofibroblasts in tumour stroma is probably typical for cases with worse prognosis

Multivariate analysis of oestrogen receptor alpha, pS2, metallothionein and CD24 expression in invasive breast cancers

Determination of oestrogen receptor alpha (ER) represents at present the most important predictive factor in breast cancers. Data of ours and of other authors suggest that promising predictive/prognostic factors may also include pS2, metallothionein (MT) and CD24. Present study aimed at determining prognostic and predictive value of immunohistochemical determination of ER, pS2, MT, and CD24 expression in sections originating from 104 patients with breast cancer. An univariate and multivariate analysis was performed. Both univariate and multivariate analyses demonstrated that cytoplasmic-membranous expression of CD24 (CD24c-m) represents a strong unfavourable prognostic factor in the entire group and in most of the subgroups of patients. In several subgroups of the patients also a prognostic value was demonstrated of elevated expression of pS2 and of membranous expression of CD24. Our studies demonstrated that all patients with good prognostic factors (higher ER and pS2 expressions, lower MT expression, CD24c-m negativity) survived total period of observation (103 months). The study documented that cytoplasmic-membranous expression of CD24 represented an extremely strong unfavourable prognostic factor in breast cancer. Examination of the entire panel of the studied proteins permitted to select a group of patients of an exceptionally good prognosis

Particulate matter Air Pollution induces hypermethylation of the p16 promoter Via a mitochondrial ROS-JNK-DNMT1 pathway

Exposure of human populations to chronically elevated levels of ambient particulate matter air pollution < 2.5 μm in diameter (PM2.5) has been associated with an increase in lung cancer incidence. Over 70% of lung cancer cell lines exhibit promoter methylation of the tumor suppressor p16, an epigenetic modification that reduces its expression. We exposed mice to concentrated ambient PM2.5 via inhalation, 8 hours daily for 3 weeks and exposed primary murine alveolar epithelial cells to daily doses of fine urban PM (5 µg/cm2). In both mice and alveolar epithelial cells, PM exposure increased ROS production, expression of the DNA methyltransferase 1 (DNMT1), and methylation of the p16 promoter. In alveolar epithelial cells, increased transcription of DNMT1 and methylation of the p16 promoter were inhibited by a mitochondrially targeted antioxidant and a JNK inhibitor. These findings provide a potential mechanism by which PM exposure increases the risk of lung cancer

PM2.5 metal exposures and nocturnal heart rate variability: a panel study of boilermaker construction workers

<p>Abstract</p> <p>Background</p> <p>To better understand the mechanism(s) of particulate matter (PM) associated cardiovascular effects, research priorities include identifying the responsible PM characteristics. Evidence suggests that metals play a role in the cardiotoxicity of fine PM (PM_2.5) and in exposure-related decreases in heart rate variability (HRV). We examined the association between daytime exposure to the metal content of PM_2.5and night HRV in a panel study of boilermaker construction workers exposed to metal-rich welding fumes.</p> <p>Methods</p> <p>Twenty-six male workers were monitored by ambulatory electrocardiogram (ECG) on a workday while exposed to welding fume and a non-workday (baseline). From the ECG, rMSSD (square root of the mean squared differences of successive intervals) was summarized over the night (0:00–7:00). Workday, gravimetric PM_2.5samples were analyzed by x-ray fluorescence to determine metal content. We used linear mixed effects models to assess the associations between night rMSSD and PM_2.5metal exposures both with and without adjustment for total PM_2.5. Matched ECG measurements from the non-workday were used to control for individual cardiac risk factors and models were also adjusted for smoking status. To address collinearity between PM_2.5and metal content, we used a two-step approach that treated the residuals from linear regression models of each metal on PM_2.5as surrogates for the differential effects of metal exposures in models for night rMSSD.</p> <p>Results</p> <p>The median PM_2.5exposure was 650 μg/m³; median metal exposures for iron, manganese, aluminum, copper, zinc, chromium, lead, and nickel ranged from 226 μg/m³to non-detectable. We found inverse linear associations in exposure-response models with increased metal exposures associated with decreased night rMSSD. A statistically significant association for manganese was observed, with a decline of 0.130 msec (95% CI: -0.162, -0.098) in night rMSSD for every 1 μg/m³increase in manganese. However, even after adjusting for individual metals, increases in total PM_2.5exposures were associated with declines in night rMSSD.</p> <p>Conclusion</p> <p>These results support the cardiotoxicity of PM_2.5metal exposures, specifically manganese. However the metal component alone did not account for the observed declines in night HRV. Therefore, results suggest the importance of other PM elemental components.</p

A comparison of bioclimatic conditions on Franz Josef Land (the Arctic) between the turn of the nineteenth to twentieth century and present day

The paper presents the variability of meteorological conditions: air temperature, wind speed and relative air humidity; and biometeorological indices: wind chill temperature, predicted clothing insulation and accepted level of physical activity on Franz Josef Land (in Teplitz Bay and Calm Bay) in the years 1899–1931. It employs meteorological measurements taken during four scientific expeditions to the study area. The analysis mainly covered the period October–April, for which the most complete data set is available. For that period of the year, which includes the part of the year with the Franz Josef Land’s coldest air temperatures, the range and nature of changes in meteorological and biometeorological conditions between historical periods and the modern period (1981–2010) were studied. The data analysis revealed that during the three oldest expeditions (which took place in the years 1899–1914), the biometeorological conditions in the study area were more harsh to humans than in the modern period (1981–2010) or similarly harsh. In contrast, during the 1930/1931 expedition, which represents the Early Twentieth CenturyWarming (ETCW), conditions were clearly more favourable (including predicted clothing insulation being 0.3 clo lower and 4.0 °C higher wind chill temperature than conditions observed nowadays)

Particulate Matter-Induced Lung Inflammation Increases Systemic Levels of PAI-1 and Activates Coagulation Through Distinct Mechanisms

Exposure of human populations to ambient particulate matter (PM) air pollution significantly contributes to the mortality attributable to ischemic cardiovascular events. We reported that mice treated with intratracheally instilled PM develop a prothrombotic state that requires the release of IL-6 by alveolar macrophages. We sought to determine whether exposure of mice to PM increases the levels of PAI-1, a major regulator of thrombolysis, via a similar or distinct mechanism. mice but was absent in mice treated with etanercept, a TNF-α inhibitor. Treatment with etanercept did not prevent the PM-induced tendency toward thrombus formation.Mice exposed to inhaled PM exhibited a TNF-α-dependent increase in PAI-1 and an IL-6-dependent activation of coagulation. These results suggest that multiple mechanisms link PM-induced lung inflammation with the development of a prothrombotic state