Photoacoustic Sentinel Lymph Node Imaging with Self-Assembled Copper Neodecanoate Nanoparticles

Photoacoustic tomography (PAT) is emerging as a novel, hybrid, and non-ionizing imaging modality because of its satisfactory spatial resolution and high soft tissue contrast. PAT combines the advantages of both optical and ultrasonic imaging methods. It opens up the possibilities for noninvasive staging of breast cancer and may replace sentinel lymph node (SLN) biopsy in clinic in the near future. In this work, we demonstrate for the first time that copper can be used as a contrast metal for near-infrared detection of SLN using PAT. A unique strategy is adopted to encapsulate multiple copies of Cu as organically soluble small molecule complexes within a phospholipid-entrapped nanoparticle. The nanoparticles assumed a size of 80–90 nm, which is the optimum hydrodynamic diameter for its distribution throughout the lymphatic systems. These particles provided at least 6-fold higher signal sensitivity in comparison to blood, which is a natural absorber of light. We also demonstrated that high SLN detection sensitivity with PAT can be achieved in a rodent model. This work clearly demonstrates for the first time the potential use of copper as an optical contrast agent

Photoacoustic Sentinel Lymph Node Imaging with Self-Assembled Copper Neodecanoate Nanoparticles

Photoacoustic tomography (PAT) is emerging as a novel, hybrid, and non-ionizing imaging modality because of its satisfactory spatial resolution and high soft tissue contrast. PAT combines the advantages of both optical and ultrasonic imaging methods. It opens up the possibilities for noninvasive staging of breast cancer and may replace sentinel lymph node (SLN) biopsy in clinic in the near future. In this work, we demonstrate for the first time that copper can be used as a contrast metal for near-infrared detection of SLN using PAT. A unique strategy is adopted to encapsulate multiple copies of Cu as organically soluble small molecule complexes within a phospholipid-entrapped nanoparticle. The nanoparticles assumed a size of 80–90 nm, which is the optimum hydrodynamic diameter for its distribution throughout the lymphatic systems. These particles provided at least 6-fold higher signal sensitivity in comparison to blood, which is a natural absorber of light. We also demonstrated that high SLN detection sensitivity with PAT can be achieved in a rodent model. This work clearly demonstrates for the first time the potential use of copper as an optical contrast agent

The Effect of PEI-PA Hemoglobin Nanoparticles on Blood Rheology

Mentor: Gregory Lanza From the Washington University Undergraduate Research Digest: WUURD, Volume 6, Issue 2, Spring 2011. Published by the Office of Undergraduate Research, Joy Zalis Kiefer Director of Undergraduate Research and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Editor

Cancer cell cycle modulation by metabolic gene expression and role of photoreceptor phosphodiesterase 6H in cancer cell growth

While the deregulation of cancer metabolism through oncogenic signalling, and the effect of the latter on proliferation and cell cycle control are widely studied, little is known on how metabolism in cancer cells leads to cell cycle control and progression. This project aimed to identify metabolic genes whose inhibition causes cell cycle arrest, which would allow further study of candidate genes in the context of cancer metabolism and cell proliferation. The screen was conducted with a custom siRNA library targeting metabolic genes commonly amplified in primary tumours, as well as those known to be involved in the key regulatory points of metabolic pathways. Results show that TCA cycle, fatty acid metabolism and nucleotide metabolism are especially important during the transition into S phase, whereas enzymes of electron transport chain, glycolysis and pentose phosphate pathway are significant for the completion of both G1 and G2 phases. Among the genes whose knockdown caused G1, cone phosphodiesterase 6H (PDE6H) of the retina was selected for further study as a novel controller of cancer cell cycle and metabolism, recognised for a role in controlling retinal metabolism. Besides causing G1 cell cycle arrest and disruption of G1/S checkpoint mechanism, PDE6H knockdown induced apoptosis and mitochondrial dysfunction. PDE6H depletion also inhibited cell proliferation and lowered basal levels of cellular metabolism. In xenograft experiments of PDE6H CRISPR/Cas9 knockout HCT116 cells we showed that PDE6H deletion slowed down tumour growth and improved animal survival. PDE6 inhibition via a drug, zaprinast, caused similar increase in tumour hypoxia and necrosis as well as an inhibition of tumour cell proliferation. Our results report PDE6H as a controller of cancer cell metabolism and proliferation, making it a potential target for therapy.</p

The Reverse Operation Of Knot Digraph Notation

It is well known that bitopologies associated with knot digraphs is finded by using knot digraph notation. In this work, we have developed a method that we called reverse of knot digraph notation to find out which knot belongs to when a bitopology associated with the knot is given

The Reverse Operation Of Knot Digraph Notation

It is well known that bitopologies associated with knot digraphs is finded by using knot digraph notation. In this work, we have developed a method that we called reverse of knot digraph notation to find out which knot belongs to when a bitopology associated with the knot is given

Cone photoreceptor phosphodiesterase PDE6H inhibition regulates cancer cell growth and metabolism, replicating the dark retina response

Abstract Background PDE6H encodes PDE6γ′, the inhibitory subunit of the cGMP-specific phosphodiesterase 6 in cone photoreceptors. Inhibition of PDE6, which has been widely studied for its role in light transduction, increases cGMP levels. The purpose of this study is to characterise the role of PDE6H in cancer cell growth. Methods From an siRNA screen for 487 genes involved in metabolism, PDE6H was identified as a controller of cell cycle progression in HCT116 cells. Role of PDE6H in cancer cell growth and metabolism was studied through the effects of its depletion on levels of cell cycle controllers, mTOR effectors, metabolite levels, and metabolic energy assays. Effect of PDE6H deletion on tumour growth was also studied in a xenograft model. Results PDE6H knockout resulted in an increase of intracellular cGMP levels, as well as changes to the levels of nucleotides and key energy metabolism intermediates. PDE6H knockdown induced G1 cell cycle arrest and cell death and reduced mTORC1 signalling in cancer cell lines. Both knockdown and knockout of PDE6H resulted in the suppression of mitochondrial function. HCT116 xenografts revealed that PDE6H deletion, as well as treatment with the PDE5/6 inhibitor sildenafil, slowed down tumour growth and improved survival, while sildenafil treatment did not have an additive effect on slowing the growth of PDE6γ′-deficient tumours. Conclusions Our results indicate that the changes in cGMP and purine pools, as well as mitochondrial function which is observed upon PDE6γ′ depletion, are independent of the PKG pathway. We show that in HCT116, PDE6H deletion replicates many effects of the dark retina response and identify PDE6H as a new target in preventing cancer cell proliferation and tumour growth