Multidrug resistance protein 1 localization in lipid raft domains and prostasomes in prostate cancer cell lines

Background: One of the problems in prostate cancer (CaP) treatment is the appearance of the multidrug resistance phenotype, in which ATP-binding cassette transporters such as multidrug resistance protein 1 (MRP1) play a role. Different localizations of the transporter have been reported, some of them related to the chemoresistant phenotype. Aim: This study aimed to compare the localization of MRP1 in three prostate cell lines (normal, androgen-sensitive, and androgen-independent) in order to understand its possible role in CaP chemoresistance. Methods: MRP1 and caveolae protein markers were detected using confocal microscopy, performing colocalization techniques. Lipid raft isolation made it possible to detect these proteins by Western blot analysis. Caveolae and prostasomes were identified by electron microscopy. Results: We show that MRP1 is found in lipid raft fractions of tumor cells and that the number of caveolae increases with malignancy acquisition. MRP1 is found not only in the plasma membrane associated with lipid rafts but also in cytoplasmic accumulations colocalizing with the prostasome markers Caveolin-1 and CD59, suggesting that in CaP cells, MRP1 is localized in prostasomes. Conclusion: We hypothesize that the presence of MRP1 in prostasomes could serve as a reservoir of MRP1; thus, taking advantage of the release of their content, MRP1 could be translocated to the plasma membrane contributing to the chemoresistant phenotype. The presence of MRP1 in prostasomes could serve as a predictor of malignancy in Ca

Early experience and quality of life in SBRT prostate cancer boost of 9 Gy in a phase II trial

Purpose or ObjectiveExtracranial stereotactic body radiation therapy (SBRT) allows delivering high doses per fraction with high accuracy to the prostatic gland in a low number of fractions.Dose escalation in normofractionaded radiation prostate cancer trials showed an increased toxicity.In order to evaluate the feasibility and toxicity of a regimen of a single dose hypofractionated prostate stereotactic boost a phase II study was undertaken. Self-reported quality of life (QOL) measures were also obtained in order to better define the possible deleterious effect of treatment

Oxygen Absorption in Free-Standing Porous Silicon: A Structural, Optical and Kinetic Analysis

Porous silicon (PSi) is a nanostructured material possessing a huge surface area per unit volume. In consequence, the adsorption and diffusion of oxygen in PSi are particularly important phenomena and frequently cause significant changes in its properties. In this paper, we study the thermal oxidation of p+-type free-standing PSi fabricated by anodic electrochemical etching. These free-standing samples were characterized by nitrogen adsorption, thermogravimetry, atomic force microscopy and powder X-ray diffraction. The results show a structural phase transition from crystalline silicon to a combination of cristobalite and quartz, passing through amorphous silicon and amorphous silicon-oxide structures, when the thermal oxidation temperature increases from 400 to 900 °C. Moreover, we observe some evidence of a sinterization at 400 °C and an optimal oxygen-absorption temperature about 700 °C. Finally, the UV/Visible spectrophotometry reveals a red and a blue shift of the optical transmittance spectra for samples with oxidation temperatures lower and higher than 700 °C, respectively

Lung resistance-related protein as a predictor of clinical outcome in advanced testicular germ-cell tumours

This study was undertaken to investigate the expression and predictive value for outcome of multidrug resistance-associated (MDR) proteins P-glycoprotein (Pgp), MRP1, BCRP, and LRP, in advanced testicular germ-cell tumours (TGCT). Paraffin-embedded sections from 56 previously untreated patients with metastatic TGCT were immunostained for Pgp, MRP1, BCRP, and LRP. All patients received platinum-based chemotherapy after orchidectomy. Immunostaining was related to clinicopathological parameters, response to chemotherapy, and outcome. Strong and intermediate expressions of the different MDR-related proteins were: 27 and 41% (Pgp), 54 and 37% (MRP1), 86 and 7% (BCRP), and 14 and 29% (LRP). P-glycoprotein and MRP1 associated, respectively, to low AFP (P=0.026) and high LDH levels (P=0.014), whereas LRP expression associated with high beta-hCG levels (P=0.003) and stage IV tumours (P=0.029). No correlation was found between Pgp, MRP1, and BCRP expression and response to chemotherapy and survival. In contrast, patients with LRP-positive tumours (strong or intermediate expression) had shorter progression-free (P=0.0006) and overall survival (P=0.0116) than LRP-negative patients, even after individual log-rank adjustments by statistically associated variables. Our data suggest that a positive LRP immunostaining at the time of diagnosis in metastatic TGCT is associated with an adverse clinical outcome

Review article of the current state of glaciers in the tropical Andes: a multi-century perspective on glacier evolution and climate change

The aim of this paper is to provide the community with a comprehensive overview of the studies of glaciers in the tropical Andes conducted in recent decades leading to the current status of the glaciers in the context of climate change. In terms of changes in surface area and length, we show that the glacier retreat in the tropical Andes over the last three decades is unprecedented since the maximum extension of the LIA (mid 17th–early 18th century). In terms of changes in mass balance, although there have been some sporadic gains on several glaciers, we show that the trend has been quite negative over the past 50 yr, with a mean mass balance deficit for glaciers in the tropical Andes that is slightly more negative than the computed global average. A break point in the trend appeared in the late 1970s with mean annual mass balance per year decreasing from −0.2m w.e. in the period 1964–1975 to −0.76m w.e. in the period 1976–2010. In addition, even if glaciers are currently retreating everywhere in the tropical Andes, it should be noted that as a percentage, this is much more pronounced on small glaciers at low altitudes that do not have a permanent accumulation zone, and which could disappear in the coming years/decades. Monthly mass balance measurements performed in Bolivia, Ecuador and Colombia showed that variability of the surface temperature of the Pacific Ocean is the main factor governing variability of the mass balance variability at the interannual to decadal time scale. Precipitation did not display a significant trend in the tropical Andes in the 20th century, and consequently cannot explain the glacier recession. On the other hand, temperature increased at a significant rate of 0.10◦Cdecade−1 in the last 70 yr. The higher frequency of El Nin ̃o events and changes in its spatial and temporal occurrence since the late 1970s together with a warming troposphere over the tropical Andes may thus explain much of the recent dramatic shrinkage of glaciers in this part of the world

Primary large-cell neuroendocrine carcinoma of the penis: association with human papilloma virus infection

10.1111/j.1365-2559.2012.04256.

Contribution of glacier runoff to water resources of La Paz city, Bolivia (16 degrees S)

The supply of glacier water to La Paz city, Bolivia, between 1963 and 2006 was assessed at annual and seasonal timescales based on the mass-balance quantification of 70 glaciers located within the drainage basins of La Paz. Glaciers contributed similar to 15% of water resources at an annual scale (14% in the wet season, 27% in the dry season). Uncertainties in our estimation are related to the assumed constant precipitation (similar to 0.5% for ice-free areas and up to 6.5% for glaciated areas), the constant runoff coefficient (similar to 1%), the surface areas of the glaciers and catchments (similar to 5%) and the mean mass-balance uncertainty of the 21 glaciers used to obtain the mass balance of the 70 glaciers (12% of the total discharge). Despite the loss of 50% of the glacierized area during the study period, runoff at La Paz did not change significantly, showing that increase in ice melt rates compensated for reduction in the surface area of the glaciers. In the future, assuming complete disappearance of the glaciers and no change in precipitation, runoff should diminish by similar to 12% at an annual scale, 9% during the wet season and 24% during the dry season