Purpose Malignant cancer foci develop acidic extracellular environments. Mild acidic conditions trigger insertion and folding of the pH (low) insertion peptide (pHLIP™) across a cellular membrane, enabling targeting of such lesions. Procedures We employed optical imaging to follow targeting by fluorescent pHLIP given i.v. in mice. For visualization, Cy5.5 and Alexa750 were covalently attached to the N terminus of pHLIP, which stays outside of a cell membrane after transmembrane insertion. Results We demonstrate that pHLIP targets: (a) tumors of different origins established by subcutaneous injection of cancer cells, (b) spontaneous prostate tumors in TRAMP mice and (c) metastatic lesions in lung. pHLIP accumulation in tumors correlates with tumor aggressiveness. Within a tumor, it stains extracellular spaces and cellular membranes. Conclusions Tissue acidity can be detected by pHLIP peptide insertion and used to diagnose primary tumors, metastatic lesions, and lipid bodies in necrotic tissues. The ability of pHLIP to differentially bind metastatic and non-metastatic tumors may provide a new approach for evaluating cancer prognosis.

Progress in nanomedicine depends on the development of nanomaterials and targeted delivery methods. In this work, we describe a method for the preferential targeting of gold nanoparticles to a tumor in a mouse model. The method is based on the use of the pH Low Insertion Peptide (pHLIP), which targets various imaging agents to acidic tumors. We compare tumor targeting by nonfunctionalized nanogold particles with nanogold–pHLIP conjugates, where nanogold is covalently attached to the N terminus of pHLIP. Our most important finding is that both intratumoral and i.v. administration demonstrated a significant enhancement of tumor uptake of gold nanoparticles conjugated with pHLIP. Statistically significant reduction of gold accumulation was observed in acidic tumors and kidney when pH-insensitive K-pHLIP was used as a vehicle, suggesting an important role of pH in the pHLIP-mediated targeting of gold nanoparticles. The pHLIP technology can substantially improve the delivery of gold nanoparticles to tumors by providing specificity of targeting, enhancing local concentration in tumors, and distributing nanoparticles throughout the entire tumor mass where they remain for an extended period (several days), which is beneficial for radiation oncology and imaging.

Prostate cancer is the second most common cancer globally in men, and in some countries is now the most diagnosed form of cancer. It is necessary to differentiate between benign and malignant prostate conditions to give accurate diagnoses. We aim to demonstrate the use of a 3D Mueller matrix method to allow quick and easy clinical differentiation between prostate adenoma and carcinoma tissues with different grades and Gleason scores. Histological sections of benign and malignant prostate tumours, obtained by radical prostatectomy, were investigated. We map the degree of depolarisation in the different prostate tumour tissues using a Mueller matrix polarimeter set-up, based on the superposition of a reference laser beam with the interference pattern of the sample in the image plane. The depolarisation distributions can be directly related to the morphology of the biological tissues. The dependences of the magnitude of the 1st to 4th order statistical moments of the depolarisation distribution are determined, which characterise the distributions of the depolarisation values. To determine the diagnostic potential of the method three groups of histological sections of prostate tumour biopsies were formed. The first group contained 36 adenoma tissue samples, while the second contained 36 carcinoma tissue samples of a high grade (grade 4: poorly differentiated—4 + 4 Gleason score), and the third group contained 36 carcinoma tissue samples of a low grade (grade 1: moderately differentiated—3 + 3 Gleason score). Using the calculated values of the statistical moments, tumour tissues are categorised as either adenoma or carcinoma. A high level (> 90%) accuracy of differentiation between adenoma and carcinoma samples was achieved for each group. Differentiation between the high-grade and low-grade carcinoma samples was achieved with an accuracy of 87.5%. The results demonstrate that Mueller matrix mapping of the depolarisation distribution of prostate tumour tissues can accurately differentiate between adenoma and carcinoma, and between different grades of carcinoma. This represents a first step towards the implementation of 3D Mueller matrix mapping for clinical analysis and diagnosis of prostate tumours.

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BackgroundNORE1A and RASSF1A are growth and tumour suppressors inactivated in a variety of cancers. Methylation of NORE1A and RASSF1A promoters is the predominant mechanism for downregulation of these proteins; however, other mechanisms are likely to exist.Methodology/Principal FindingsHere we describe a proteolysis of NORE1A and RASSF1A by calpains as alternative mechanism of their downregulation. Extracts of H358 cell line, a human bronchoalveolar carcinoma, and H460, a large cell carcinoma, were capable of proteolysis of NORE1A protein in the calpain-dependent manner. Likewise, RASSF1A tumor suppressor was proteolyzed by the H358 cell extract. Addition of calpain inhibitor to H358 and H460 cells growing in tissue culture resulted in re-expression of endogenous NORE1A. A survey of 10 human lung tumours revealed that three of them contain an activity capable of inducing NORE1A degradation.Conclusions/SignificanceThus, degradation by calpains is a novel mechanism for downregulation of NORE1A and RASSF1A proteins and might be the mechanism allowing cancer cells to escape growth suppression.

The structure and functions of endothelial cells after space mission were studied by electron and laser confocal microscopy, image analysis, and MTT test. The endothelial cells changed significantly (proliferative activity, size, contours, shape, distribution of mitochondria and microtubules) in comparison with controls on the Earth. These changes indicated injuries in the cytoskeleton and impairment of the barrier function of the cells, which presumably contributed to the development of endothelial dysfunction.

In this work, we apply generative topographic maps as a universal approach for data visualization and structure–property modeling of melting points (mp), which is one of the most important physical properties for the design and application of ionic liquids (ILs) as green solvents. Data visualization is part of a more general concept of chemography, which is a relatively new field dealing with visualization of chemical data, representation of chemical space, and navigation in this space. This field has received much attention by chemists as it may help to analyze and to intuitively comprehend relevant molecular features and relationships. In this study, to our knowledge for the first time, we proposed the universal approach that can be used both for the visualization of the chemical space of ILs according to their melting point values and for the development of the classification models able to predict the melting points of novel ILs. The structurally diverse data set of 717 ILs containing bromides of nitrogen-containing organic cations and including 126 pyridinium bromides (PYR), 384 imidazolium and benzoimidazolium bromides (IMZ), and 207 quaternary ammonium bromides (QUAT) was involved in model development. This study was carried out in several descriptor spaces analyzing the impact of descriptor choice. The clear criteria for data visualization and classification quality were used to assess the performance of the developed models.

The impairments of cerebral blood flow microcirculation brought on by cardiac and respiratory arrest were assessed with multi‐modal diagnostic facilities, utilising laser speckle contrast imaging, fluorescence spectroscopy and diffuse reflectance spectroscopy. The results of laser speckle contrast imaging show a notable reduction of cerebral blood flow in small and medium size vessels during a few minutes of respiratory arrest, while the same effect was observed in large sinuses and their branches during the circulatory cessation. Concurrently, the redox ratio assessed with fluorescence spectroscopy indicates progressing hypoxia, NADH accumulation and increase of FAD consumption. The results of diffuse reflectance spectra measurements display a more rapid grow of the perfusion of deoxygenated blood in case of circulatory impairment. In addition, consequent histopathological analysis performed by using new tissue staining procedure developed in‐house. It shows notably higher reduction of size of the neurons due to their wrinkling within brain tissues influenced by circulation impair. Whereas, the brain tissues altered with the respiratory arrest demonstrate focal perivascular oedema and mild hypoxic changes of neuronal morphology. Thus, the study suggests that consequences of a cessation of cerebral blood flow become more dramatic and dangerous compare to respiratory arrest.