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.     

Myopathy-Sensitive G-Actin Segment 227-235 Is Involved in Salt-Induced Stabilization of Contacts within the Actin Filament

Formation of stable actin filaments, critically important for actin functions, is determined by the ionic strength of the solution. However, not much is known about the elements of the actin fold involved in ionic-strength-dependent filament stabilization. In this work, F-actin was destabilized by Cu²⁺ binding to Cys374, and the effects of solvent conditions on the dynamic properties of F-actin were correlated with the involvement of Segment 227-235 in filament stabilization. The results of our work show that the presence of Mg²⁺ at the high-affinity cation binding site of Cu-modified actin polymerized with MgCl₂ strongly enhances the rate of filament subunit exchange and promotes the filament instability. In the presence of 0.1 M KCl, the filament subunit exchange was 2–3-fold lower than that in the MgCl₂-polymerized F-actin. This effect correlates with the reduced accessibility of the D-loop and Segment 227-235 on opposite filament strands, consistent with an ionic-strength-dependent conformational change that modulates involvement of Segment 227-235 in stabilization of the intermonomer interface. KCl may restrict the mobility of the α-helix encompassing part of Segment 227-235 and/or be bound to Asp236 at the boundary of Segment 227-235. These results provide experimental evidence for the involvement of Segment 227-235 in salt-induced stabilization of contacts within the actin filament and suggest that they can be weakened by mutations characteristic of actin-associated myopathies.     

Solitary metastasis of a clear cell renal cell carcinoma after a 20 year latency clinically simulating a vascular tumor

HISTORY AND CLINICAL FINDINGS: A 72-year-old woman was referred because of progressive skin discoloration with venectasia and swelling in the left lower leg, the possible diagnosis being atypical varicose veins. 20 years before she had a right nephrectomy for "clear-cell" renal adenocarcinoma with subsequent tele-cobalt radiotherapy. On examination a pulsating swelling was palpated over the hyperpigmented area of the skin with venectasia. INVESTIGATIONS: She had hypercholesterolaemia (254 mg/dl) and hyperuricaemia (uric acid 6.2 mg/dl). Duplex sonography, angiography and computed tomography of the lower leg revealed a vascular tumour with infiltration of the right head of the gastrocnemius. DIAGNOSIS, TREATMENT AND COURSE: Because an arteriovenous fistula within a vascular soft-tissue tumour of unknown histology was suspected, a wide resection was performed. Histopathological examination revealed a metastasis of a clear-cell adenocarcinoma. Postoperative diagnostic tests discovered no other findings suspicious of malignancy. It is therefore to be assumed that the resected tumour was a solitary metastasis of the renal adenocarcinoma removed 20 years previously. CONCLUSION: Even rare causes should be considered in the differential diagnosis of vascular tumour, as this case of a solitary metastasis after a latency of 20 years demonstrates.     

Visualization and quantification of myocardial mass at risk using three-dimensional contrast echocardiography

To investigate possible biochemical mechanisms underlying the "toxic gain of function" associated with polyglutamine expansions, the ability of guinea pig liver tissue transglutaminase to catalyze covalent attachments of various polyamines to polyglutamine peptides was examined. Of the polyamines tested, spermine is the most active substrate, followed by spermidine and putrescine. Formation of covalent cross links between polyglutamine peptides and polyamines yields high-M(r) aggregates--a process that is favored with longer polyglutamines. In the presence of tissue transglutaminase, purified glyceraldehyde-3-phosphate dehydrogenase (a key glycolytic enzyme that binds tightly to the polyglutamine domains of both huntingtin and dentatorubral-pallidoluysian atrophy proteins) is covalently attached to polyglutamine peptides in vitro, resulting in the formation of high-M(r) aggregates. In addition, endogenous glyceraldehyde-3-phosphate dehydrogenase of a Balb-c 3T3 fibroblast cell line overexpressing human tissue transglutaminase forms cross-links with a Q60 polypeptide added to the cell homogenate. Possibly, expansion of polyglutamine domains (thus far known to occur in the gene products associated with at least seven neurodegenerative diseases) leads to increased/aberrant tissue transglutaminase-catalyzed cross-linking reactions with both polyamines and susceptible proteins, such as glyceraldehyde-3-phosphate dehydrogenase. Formation of cross-linked heteropolymers may lead to deposition of high-M(r) protein aggregates, thereby contributing to cell death.     

Magnetic Field Stabilization for Magnetically Shielded Volumes by External Field Coils

For highly sensitive magnetic measurements, e.g., a measurement of the neutron electric dipole moment (EDM), the magnetic field has to be stable in time on a level below picoTesla. One of several measures we employ to achieve this uses an external field coil system which can stabilize the ambient external field at a predefined value. Here we report on the construction and characterization of such a system in the magnetic test facility at PSI. The system actively stabilizes the field along the axis of the EDM experiment by means of four coils in a Helmholtz-like configuration. Additional coils serve to compensate for transverse ambient field components. Because of the long integration times in the EDM experiment (about 100 s or more) only slow disturbances have to be corrected for. The performance of the system has been measured using static and moving magnetic sources and suppression factors in excess of 200 have been observed.     

Changes in Molecular Characteristics of Cereal Carbohydrates after Processing and Digestion

Different extraction, purification and digestion methods were used to investigate the molecular properties of carbohydrates in arabinoxylan and β-glucan concentrates, dietary fiber (DF) rich breads and ileum content of bread fed pigs. The breads studied were: a low DF wheat bread (WF), whole meal rye bread (GR), rye bread with kernels (RK), wheat bread supplemented with wheat arabinoxylan concentrate (AX) and wheat bread supplemented with oat β-glucan concentrate (BG). The weight average molecular weight (M_w) of extractable carbohydrates in β-glucan concentrate decreased eight-fold after inclusion in the BG bread when exposed to in vitro digestion, while the M_w of purified extractable carbohydrates in AX bread was reduced two-fold, and remained almost unaffected until reaching the terminal ileum of pigs. Similarly, the M_w of purified extractable carbohydrates in GR and RK bread was not significantly changed in the ileum. The AX bread resulted in the highest concentration of dissolved arabinoxylan in the ileum among all the breads that caused a substantial increased in ileal AX viscosity. Nevertheless, for none of the breads, the M_w of extractable carbohydrates was related neither to the bread extract nor ileal viscosity.     

Studies of cardiac function and myocardial tissue characterization

The heart can be studied using ultrasound techniques. The shape of the heart, its chambers, wall thicknesses, wall tissue characteristics as well as motion of walls and valve leaflets are all diagnostic information. In addition, the blood velocity and its timing within the cardiac cycle is an important diagnostic tool. In the present paper focus will be limited to the analysis of the left ventricular function as observed with two-dimensional and three-dimensional echocardiography and the characteristics of backscattered ultrasound information from the left ventricular chamber wall. Function of the heart is often studied by observation of local wall motion or comparison of chamber volume in maximum and minimum shapes during the cardiac cycle (ejection fraction). Integrated backscatter from the wall is described in examples of cardiac transplantation and hypertrophy. Study of cyclic variation of frequency-dependent attenuation and integrated backscatter indicates that these are independent parameters.     

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.     

双曝光全息术用于兔子输卵管特性研究

用单模氩离子激光器拍摄了离休兔子输卵管的双曝光全息相干图。实验结果给出了正常输卵管与非正常输卵管在相干条纹形状上的差异以及相干条纹与溶液、压力及压力传递方向的关系。通过建立数学模型,对输卵管的形变作了定性分析。