Induction of ErbB-3 Expression by α6β4 Integrin Contributes to Tamoxifen Resistance in ERβ1-Negative Breast Carcinomas

Background

Tamoxifen is still the most widely used drug in hormone therapy for the treatment of breast cancer. Its benefits in adjuvant treatment are well documented in controlled and randomized clinical studies, which have demonstrated an increase in disease-free intervals of patients with positive hormonal receptors. However, the mechanisms involved in endocrine resistance are not clear. Laboratory and clinical data now indicate that bi-directional molecular cross-talk between nuclear or membrane ER and growth factor receptor pathways may be involved in endocrine resistance. We recently found a functional interaction between α6β4 integrin and ErbB-3 receptor to maintain the PI3K/Akt survival pathway of mammary tumour cells. We sought to improve understanding of this process in order to provide the involvement of both receptors insight into mechanism of Tamoxifen resistance.

Methods and Findings

Using human breast cancer cell lines displaying different levels of α6β4 and ErbB-3 receptors and a series of 232 breast cancer biopsies from patients submitted to adjuvant Tamoxifen monotherapy for five years, we evaluated the functional interaction between both receptors in relationship to Tamoxifen responsiveness. In mammary carcinoma cells, we evidenced that the α6β4 integrin strongly influence Akt phosphorylation through ErbB-3 protein regulation. Moreover, the ErbB-3 inactivation inhibits Akt phosphorylation, induces apoptosis and inhibits in vitro invasion favouring Tamoxifen responsiveness. The analysis of human tumors revealed a significant relationship between α6β4 and ErbB-3 in P-Akt-positive and ERβ1-negative breast cancers derived from patients with lower disease free survival.

Conclusions

We provided evidence that a strong relationship occurs between α6β4 and ErbB-3 positivity in ERβ1-negative breast cancers. We also found that the association between ErbB-3 and P-Akt positivity mainly occurs in ERβ1-negative breast cancer derived from patients with lower DFS indicating that both receptors are clinically relevant in predicting the response to Tamoxifen.     

Chemical Characterization and Biological Activities of Phenolic‐Rich Fraction from Cauline Leaves of Isatis tinctoria L. (Brassicaceae) Growing in Sicily,Italy

The present work focused on the evaluation of the antioxidant and cytotoxic activities of the phenolic‐rich fraction (ItJ‐EAF) obtained from cauline leaves collected in January from Isatis tinctoria L. (Brassicaceae) growing wild around Acireale (Sicily, Italy). The total phenolic, flavonoid, and condensed tannin contents of the fraction were determined spectrophotometrically, whereas the phenolic profile was assessed by HPLC‐PDA/ESI‐MS analysis. A total of 20 compounds were positively identified and twelve out of them were never previously reported in I. tinctoria leaves. The fraction exhibited good radical scavenging activity in DPPH test (IC₅₀ = 0.6657 ± 0.0024 mg/ml) and reducing power (3.87 ± 0.71 ASE/ml), whereas, it neither showed chelating activity nor was able to counteract H₂O₂ induced oxidative stress damage in Escherichia coli. The antiproliferative effect was evaluated in vitro on two human anaplastic thyroid carcinoma cell lines (CAL‐62 and 8505C) by MTT assay. At the highest tested concentration ItJ‐EAF significantly reduced (80%) the growth of CAL‐62 cells. No cytotoxicity against Artemia salina was observed. It can be concluded that I. tinctoria cauline leaves represent a source of phenolic compounds which could be potentially used as chemopreventive or adjuvant agents against cancer.     

Are aquatic assemblages from small water bodies more stochastic in dryer climates? An analysis of ostracod spring metacommunities

Metacommunity ecology describes community organisation considering both environmental and spatial processes. We tested the relative importance of environmental and spatial factors on spring ostracod assemblages from four European regions characterised by different climatic conditions (e.g. aridity). Pure and shared effects of environment and space were calculated using redundancy analysis and variation partitioning. Both environmental and spatial variables significantly explain assemblage variation, although with different relevance among areas. The amount of variation explained by environmental factors decreased with increasing climate aridity. The reduced size of spring habitats makes them prone to drying events, which are more frequent in dryer climates. Frequent disturbances may lead to local extinctions followed by colonisations from nearby sites, in a source–sink dynamics. Early recolonisation leads to random assemblages and reduces the match between organisms and environmental conditions. As a consequence, a low amount of community variation can be explained by environmental variables. Conversely, the settled communities from wetter climates best fit the ecological characteristics of sites, and deterministic processes, such as species sorting, dominate the assemblages. In conclusion, in the studied regions, ostracod communities from small water bodies of dryer climates seem to be mainly driven by stochastic dynamics when compared to more continental areas.     

Bee pollination and evidence of substitutive nectary in <Emphasis Type="Italic">Anadenanthera colubrina</Emphasis> (Leguminosae-Mimosoideae)

Anadenanthera colubrina (Vell.) Brenan (Leguminosae-Mimosoideae) is a widely-distributed tree in seasonally dry tropical forests of South America that was classified previously as lacking nectaries. However, some studies have stated that its flowers produce nectar, while others analyzed the composition of unifloral honey produced from A. colubrina flowers, raising the question about nectar production in the species. We studied the pollination and reproductive biology of A. colubrina var. cebil (Griseb.) Altschul in a natural population in the Caatinga, northeastern Brazil. Reproductive phenology, sexual system, floral biology, resource, and pollinators were investigated. We analyzed the breeding system through controlled pollinations for addressing its dependence on pollen vectors for reproduction. Anadenanthera colubrina flowered in the dry season, flower heads are heteromorphic, with staminate flowers at the base and perfect flowers at the apex of the inflorescence, characterizing andromonoecy. Anthesis is diurnal. We observed small drops of nectar at the apex of the petals of some flowers per inflorescence. Together with observations on flower visitor behavior and histochemical tests, we propose that A. colubrina produces floral nectar at the apex of the corolla, characterizing a substitutive nectary (sensu Vogel). This is the first record of substitutive nectary in the Mimosoideae and the first record of andromonoecy in the genus. Bees were the main pollinators (higher frequency), although other insects such as wasps, butterflies, and small beetles were also observed collecting nectar and/or pollen. The species is self-incompatible, thus depending on insect pollen vectors, mainly bees, for reproduction.     

Perception and (re)framing of Urban Environments: A Methodological Reflection toward Sentient Research

Through senses, emotional and cognitive processes (i.e., perception, attention, learning, memory and language) individuals comprehend, make sense and are able to provide representations of the world and of the various spaces where social life takes place in. The main aim of this paper is to reflect critically on visual methodologies exploring how and to what extent they can (potentially) enhance not only the inspectionability of the empirical base of data but also the “degrees of reflexivity” of all those who are, directly and indirectly, involved in the research process, along all its phases, e.g., researchers, citizens, stakeholders, planners and policy-makers, etc. A secondary aim is to reflect on the possibilities visual methods provide us for a deeper and more comprehensive understanding of the urban landscapes and of the perception of phenomena and processes occurring in, shaped by and peculiar to these spaces.

In order to look at visual methodologies critically and to connect the above-mentioned objectives to “real” contexts of applications, I will re-examine two specific case studies made in the city of Milan, each of which addresses the issue of urban sustainability perception, and how this intertwines with city planning and design. Moreover, they share a common phenomenological framework and were completed some years ago.