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Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality. Despite significant advances made in the treatment of other cancers, current chemotherapies offer little survival benefit in this disease. Pancreaticoduodenectomy offers patients the possibility of a cure, but most will die of recurrent or metastatic disease. Hence, preventing metastatic disease in these patients would be of significant benefit. Using principal component analysis (PCA), we identified a LOX/hypoxia signature associated with poor patient survival in resectable patients. We found that LOX expression is upregulated in metastatic tumors from Pdx1-Cre Kras(G12D/+) Trp53(R172H/+) (KPC) mice and that inhibition of LOX in these mice suppressed metastasis. Mechanistically, LOX inhibition suppressed both migration and invasion of KPC cells. LOX inhibition also synergized with gemcitabine to kill tumors and significantly prolonged tumor-free survival in KPC mice with early-stage tumors. This was associated with stromal alterations, including increased vasculature and decreased fibrillar collagen, and increased infiltration of macrophages and neutrophils into tumors. Therefore, LOX inhibition is able to reverse many of the features that make PDAC inherently refractory to conventional therapies and targeting LOX could improve outcome in surgically resectable disease.

INTRODUCTION: Mammographic density (MD), after adjustment for a women's age and body mass index, is a strong and independent risk factor for breast cancer (BC). Although the BC risk attributable to increased MD is significant in healthy women, the biological basis of high mammographic density (HMD) causation and how it raises BC risk remain elusive. We assessed the histological and immunohistochemical differences between matched HMD and low mammographic density (LMD) breast tissues from healthy women to define which cell features may mediate the increased MD and MD-associated BC risk. METHODS: Tissues were obtained between 2008 and 2013 from 41 women undergoing prophylactic mastectomy because of their high BC risk profile. Tissue slices resected from the mastectomy specimens were X-rayed, then HMD and LMD regions were dissected based on radiological appearance. The histological composition, aromatase immunoreactivity, hormone receptor status and proliferation status were assessed, as were collagen amount and orientation, epithelial subsets and immune cell status. RESULTS: HMD tissue had a significantly greater proportion of stroma, collagen and epithelium, as well as less fat, than LMD tissue did. Second harmonic generation imaging demonstrated more organised stromal collagen in HMD tissues than in LMD tissues. There was significantly more aromatase immunoreactivity in both the stromal and glandular regions of HMD tissues than in those regions of LMD tissues, although no significant differences in levels of oestrogen receptor, progesterone receptor or Ki-67 expression were detected. The number of macrophages within the epithelium or stroma did not change; however, HMD stroma exhibited less CD206(+) alternatively activated macrophages. Epithelial cell maturation was not altered in HMD samples, and no evidence of epithelial-mesenchymal transition was seen; however, there was a significant increase in vimentin(+)/CD45(+) immune cells within the epithelial layer in HMD

The self-assembly of semiconductor quantum dots has opened up new opportunities in photonics. Quantum dots are usually described as 'artificial atoms', because electron and hole confinement gives rise to discrete energy levels. This picture can be justified from the shell structure observed as a quantum dot is filled either with excitons1 (bound electron–hole pairs) or with electrons2. The discrete energy levels have been most spectacularly exploited in single photon sources that use a single quantum dot as emitter3, 4, 5, 6. At low temperatures, the artificial atom picture is strengthened by the long coherence times of excitons in quantum dots7, 8, 9, motivating the application of quantum dots in quantum optics and quantum information processing. In this context, excitons in quantum dots have already been manipulated coherently10, 11, 12. We show here that quantum dots can also possess electronic states that go far beyond the artificial atom model. These states are a coherent hybridization of localized quantum dot states and extended continuum states: they have no analogue in atomic physics. The states are generated by the emission of a photon from a quantum dot. We show how a new version of the Anderson model that describes interactions between localized and extended states can account for the observed hybridization.

We report temperature-dependent photoluminescence on neutral and charged excitons in individual InAs quantum dots. We find narrow emission lines for temperatures up to 30 K for exciton transitions where only the electron ground state is occupied. In contrast, for doubly charged excitons where the excited electron state is occupied, we observe a drastic increase of the ground state transition linewidth even at 30 K. We interpret this as evidence that the excited electron state is degenerate with the low energy tail of continuum states.

We investigate the influence of optical pump power on a series of charging events of individual quantum dots embedded in a field effect structure. Increasing the optical pump powers moves all charging events towards more negative voltages and charged biexciton states in addition to single exciton states are observed. The linear shift in voltage with pump power is explained by the accumulation of photogenerated holes within the structure.

We have succeeded in generating highly charged excitons in InAs self-assembled quantum dots by embedding the dots in a field-effect heterostructure. We discover an excitonic Coulomb blockage: over large regions of gate voltage, the exciton charge remains constant. We present here a summary of the emission properties of the charged excitons.

A summary is presented of optical spectroscopy measurements on self-assembled quantum rings. The rings are unusual quantum dots, having a pronounced hole in the centre, and can be self-assembled during growth using a modified Stranski–Krastanowprocedure. We embed the quantum rings in a capacitor-like structure which enables us to load the quantum rings with electrons and to apply a vertical electric field. The results of these experiments, performed on a large number of individual quantumrings at lowtemperature, reveal pronounced Coulomb interactions and an excitonic Stark effect. Additionally, we have applied a magnetic field, primarily to probe the form of the lateral wave functions, but we find that this too yields insights into the Coulomb interactions. Model calculations are used to interpret these results.