The Role of Tumor Microenvironment Cells in Colorectal Cancer (CRC) Cachexia

Cancer cachexia (CC) is a multifactorial syndrome in patients with advanced cancer characterized by weight loss via skeletal-muscle and adipose-tissue atrophy, catabolic activity, and systemic inflammation. CC is correlated with functional impairment, reduced therapeutic responsiveness, and poor prognosis, and is a major cause of death in cancer patients. In colorectal cancer (CRC), cachexia affects around 50–61% of patients, but remains overlooked, understudied, and uncured. The mechanisms driving CC are not fully understood but are related, at least in part, to the local and systemic immune response to the tumor. Accumulating evidence demonstrates a significant role of tumor microenvironment (TME) cells (e.g., macrophages, neutrophils, and fibroblasts) in both cancer progression and tumor-induced cachexia, through the production of multiple procachectic factors. The most important role in CRC-associated cachexia is played by pro-inflammatory cytokines, including the tumor necrosis factor α (TNFα), originally known as cachectin, Interleukin (IL)-1, IL-6, and certain chemokines (e.g., IL-8). Heterogeneous CRC cells themselves also produce numerous cytokines (including chemokines), as well as novel factors called “cachexokines”. The tumor microenvironment (TME) contributes to systemic inflammation and increased oxidative stress and fibrosis. This review summarizes the current knowledge on the role of TME cellular components in CRC-associated cachexia, as well as discusses the potential role of selected mediators secreted by colorectal cancer cells in cooperation with tumor-associated immune and non-immune cells of tumor microenvironment in inducing or potentiating cancer cachexia. This knowledge serves to aid the understanding of the mechanisms of this process, as well as prevent its consequences.     

Hybrid lead-acid battery with reticulated vitreous carbon as a carrier- and current-collector of negative plate

Bare reticulated vitreous carbon (RVC) plated electrochemically with thin layer of lead was investigated as a negative plate carrier- and current-collector material for lead-acid batteries. Hybrid flooded single cell lead-acid batteries containing one negative plate based on a new type (RVC or Pb/RVC) of carrier/current-collector and two positive plates based on Pb-Ca grid collectors were assembled and subjected to charge/discharge tests (at 20-h and 1-h discharge rates) and Peukert's dependences determination. The promising results show that application of RVC as carrier- and current-collector in negative plate will significantly increase the specific capacity of lead-acid battery.     

“Smart” polymeric nanospheres as new materials for possible biomedical applications

Novel random terpolymers of N-isopropylacrylamide (NIPAM), sodium 2-acrylamido-2-methyl-1-propanesulfonate (AMPS), and cinnamoyloxyethylmethacrylate (CEMA) were synthesized by free radical copolymerization using AIBN as an initiator. Five terpolymers were obtained by copolymerization of the monomer mixtures containing a fixed amount of 10 mol % of AMPS while the content of CEMA ranged from 5 to 25 mol % and was changed in 5 mol % increments. The terpolymers obtained are water-soluble. Because of their amphiphilic nature they undergo self-organization in the aqueous solution with the formation of micelles capable of solubilizing sparingly water soluble organic compounds, such as drugs. The terpolymers are susceptible to three external stimuli, i.e. temperature, ionic strength and UV light. Due to the presence of NIPAM in the terpolymers they display the lower critical solution temperature (LCST), the presence of AMPS makes them sensitive to the ionic strength of the solution, while the light-responsiveness of the terpolymers is due to the presence of cinnamoyl chromophores, which undergo photodimerization when irradiated with UV light at about 280 nm. Application of any of these stimuli alone or in combination with other stimuli allows changing the copolymer properties in a controlled way.     

Accelerated weathering of pectin/poly(vinyl alcohol) blends studied by spectroscopic methods

The blends of pectin (PEC) and poly(vinyl alcohol) (PVA) at different components ratios were prepared by mixing in water. Thin polymeric films of PEC/PVA blends and pure polymers were obtained by casting method. All samples were then artificially aged using Suntest apparatus (Atlas) up to 780 h. The changes in chemical structure during sample ageing have been monitored by infrared and ultraviolet‐visible absorption spectroscopies. The first stage of weathering (up to ～ 300 h) was very slow and alteration of chemical structure was negligible in all samples. Prolonged ageing (>300 h) caused more significant degradation processes. FTIR spectra exhibited the highest changes in hydroxyl and carbonyl band ranges indicating the efficient photooxidation of macromolecules. The mechanisms of the observed processes have been discussed. It was found that PVA undergoes faster photoxidative degradation than pectin aged at the same conditions. The PEC/PVA blends exhibited the improved resistance to weathering comparing with both polymers aged individually. Mutual stabilization effect can be explained by intermolecular interactions between PEC and PVA confirmed by spectroscopic methods. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Silver nanostructured catalyst for modification of dielectrics surface

The preparation of nano-size Ag particles and their application for forming nanostructured catalysts on various surfaces are described. Silver colloid solutions were prepared by reduction of Ag(I) salt by tin(II) and characterized by electron microscopy, X-ray diffraction and light absorption spectra. Depending on the colloid preparation conditions metal particles of 5-100 nm size were obtained. According to XRD data, the colloid particles contain Ag and SnO₂ phases and no metallic Sn. The Ag nanoparticles were found to be efficient electrocatalysts for anodic oxidation of formaldehyde in alkaline solutions. The catalytic activity of a glassy carbon electrode with Ag surface coverage of 0.3-1 μg cm⁻² is similar or even exceeds that of the metallic electrode. The silver particles were used for the initiation of the electroless copper deposition process on dielectrics; for that 1-2 μg cm⁻² Ag is needed.     

Effects of aluminum and calcium on acetyl-CoA metabolism in rat brain mitochondria

Al complexes are known to accumulate in extra- and intracellular compartments of the brain in the course of different encephalopathies. In this study possible effects of Al accumulation in the cytoplasmic compartment on mitochondrial metabolism were investigated. Al, like Ca, inhibited pyruvate utilization as well as citrate and oxoglutarate accumulation by whole brain mitochondria. Potencies of Ca2+(total) effects were 10-20 times stronger than those of Al. Al decreased mitochondrial acetyl-CoA content in a concentration-dependent manner, along with an equivalent rise of free CoA level, whereas Ca caused loss of both intermediates from mitochondria. In the absence of Pi in the medium, Ca had no effect on mitochondrial metabolism, whereas Al lost its ability to suppress pyruvate utilization and acetyl-CoA content in Ca-free conditions. Verapamil potentiated, whereas ruthenium red reversed, Ca-evoked suppression of mitochondrial metabolism. On the other hand, in Ca-supplemented medium, Al partially overcame the inhibitory influence of verapamil. Accordingly, verapamil increased mitochondrial Ca levels much more strongly than Al. However, Al partially reversed the verapamil-evoked rise of Ca2+(total) level. These data indicate that Al accumulated in cytoplasm in the form of the Al(PO4)OH- complex may inhibit mitochondrial functions by an increase of intramitochondrial [Ca2+]total resulting from the Al-evoked rise of cytoplasmic [Ca2+]free, as well as from inhibitory interference with the verapamil binding site on the Na+/Ca2+ antiporter.     

Differential roles of IRS-1 and SHC signaling pathways in breast cancer cells

Several polypeptide growth factors stimulate breast cancer growth and may be involved in tumor progression. However, the relative importance of diverse growth factor signaling pathways in the development and maintenance of the neoplastic phenotype is largely unknown. The activation of such growth factor receptors as the insulin-like growth factor I receptor (IGF-I R), erbB-type receptors (erbB Rs) and FGF receptors (FGF Rs) controls the phenotype of a model breast cancer cell line MCF-7. To evaluate the function of 2 post-receptor signaling molecules, insulin receptor substrate-1 (IRS-1) (a major substrate of the IGF-IR) and SHC (a common substrate of tyrosine kinase receptors), we developed several MCF-7-derived cell clones in which the synthesis of either IRS-1 or SHC was blocked by antisense RNA. In MCF-7 cells, down-regulation of IRS-1 by 80-85% strongly suppressed anchorage-dependent and -independent growth and induced apoptotic cell death under growth factor- and estrogen-reduced conditions. The reduction of SHC levels by approximately 50% resulted in the inhibition of monolayer and anchorage-independent growth but did not decrease cell survival. Importantly, cell aggregation and the ability of cells to survive on the extracellular matrix were inhibited in MCF-7/anti-SHC clones, but not in MCF-7/anti-IRS-1 clones. Cell motility toward IGF was not attenuated in any of the tested cell lines, but motility toward EGF was decreased in MCF-7/anti-SHC clones. Our results suggest that in MCF-7 cells: 1) both IRS-1 and SHC are implicated in the control of monolayer and anchorage-independent growth; 2) IRS-1 is critical to support cell survival; 3) SHC is involved in EGF-dependent motility; and 4) normal levels of SHC, but not IRS-1, are necessary for the formation and maintenance of cell-cell interactions.     

Investigations of the electrochemical properties of activated carbon and carbon black

Potentiometric studies have been carried out on activated carbon and carbon black immersed in aqueous solutions of electrolytes. The samples studied were subjected to various modifying treatments: demineralization, oxidation in liquid and gaseous phases, saturation with hydrogen, and degassing. It was found that the potential of carbon increases during contact with the electrolyte solution; the amount of anions in the solution decreases with a simultaneous rise of the solution pH. Measurements of the potentials of the carbon samples of large specific surface area immersed in buffer solutions or solutions of established pH have shown that in the range 2.0 < pH < 7.00 the potential of the carbon material decreases with increasing pH. It was also found that the potential of the carbon powder electrode depends on the kind and concentration of the electrolyte solution as well as on the modification of the carbon surface.