Therapeutic Targets and Emerging Treatments in Advanced Chondrosarcoma

Simple SummaryChondrosarcomas develop chemoresistance to standard anticancer drugs, making it difficult to control unresectable or metastatic chondrosarcomas. To improve the clinical outcomes of chondrosarcoma, new treatment approaches, such as molecule-targeting agents and immunotherapy, are needed. Recent research has revealed promising biomarkers and therapeutic targets for chondrosarcoma. In addition, several molecule-targeting agents have shown favorable antitumor activities in several clinical studies in patients with advanced sarcomas, including chondrosarcoma. This review summarizes recent basic studies on biomarkers and therapeutic targets and recent clinical studies on treating chondrosarcomas.AbstractDue to resistance to standard anticancer agents, it is difficult to control the disease progression in patients with metastatic or unresectable chondrosarcoma. Novel therapeutic approaches, such as molecule-targeting drugs and immunotherapy, are required to improve clinical outcomes in patients with advanced chondrosarcoma. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including IDH1/2 and COL2A1. Several molecule-targeting agents and immunotherapies have shown favorable antitumor activity in clinical studies in patients with advanced chondrosarcomas. This review summarizes recent basic studies on biomarkers and molecular targets and recent clinical studies on the treatment of chondrosarcomas.     

Fracture and acoustic emission characteristics of glass fiber reinforced plastics panels for hot water

This study deals with the fracture process and acoustic emission (AE) characteristics of a randomly oriented E-glass fiber mat reinforcement with a crosslinked polyester. These panels were evaluated after they were immersed in hot water. The fiber volume content of the panel was 19%. Glass fiber reinforced plastics (GFRP) panels wer immersed in water at 81°C. Bending and AE monitoring tests were Performed and after bending, the cross-section of the specimen was observed by an optical microscope and SEM. The influence of degradation, due to water immersion, on the changes of fracture process of GFRP is discussed. The dominant fracture mode of the virgin specimen was matrix cracks, whereas that of the immersed specimen was debondings at the fiber bundle/matrix and fiber/matrix interfaces. This change was caused by reduction of the bonding strength at the interface. The scale of fracture can be estimated by both AE amplitude and AE energy and this estimation method was used to estimate the fracture mode changes of GFRP panels immersed in hot water.     

A molten metal jet impingement on a flat spreading surface

ABSTRACT

In the event of a severe accident, past experiences such as Three Mile Island and Fukushima Daichi have shown that the reactor core of a light-water nuclear reactor, if not properly safeguarded, could go through a meltdown. This will be followed by the formation of a corium, a mix of molten fuel elements, and liquid metals from the Reactor Pressure Vessel (RPV). In the worst-case scenario, a melt through from the RPV can occur and lead to the spreading of the corium, in the form of a molten element’s jet impinging on a flat concrete structure of the Primary Containment Vessel (PCV). To enhance the decommissioning and the safety procedure, scope of the present article is to deepen the understanding of the phenomena involved in the mentioned scenario, mainly jet-instability and molten material spreading. In the present study, experiments were carried out, by using corium simulant materials such as Copper and Tin, to investigate the link between the instability of the gravity-driven molten metal jet and the impinging followed by its spreading over a flat area.     

Theasaponin E1 destroys the salt tolerance of yeasts

Cells of Zygosaccharomyces rouxii in a medium containing a high concentration of NaCl were killed during incubation for 2-4 h with a low concentration of a mixture of saponins from tea seeds (TSS). The higher the concentration of NaCl in the medium, the higher the inhibitory effect of TSS on the growth of the yeast. The above inhibitory effect of TSS on the growth of the yeast was not observed when cells were incubated in hypertonic media composed of nonionic substances such as sugars. The ATPase activity of plasma membrane preparations from the yeast cells was slightly affected by the addition of TSS. It is shown that TSS facilitates leakage of glycerol from the yeast cells under NaCl-hypertonic conditions. The major inhibitor in the mixture of saponins was isolated and identified as theasaponin E1. Its isomer, theasaponin E2, did not have any effect on the salt tolerance of Z. rouxii or Saccharomyces cerevisiae.     

Release of short and proline-rich antihypertensive peptides from casein hydrolysate with an Aspergillus oryzae protease

Angiotensin-I converting enzyme inhibitory activities were measured after hydrolysis of casein by 9 different commercially available proteolytic enzymes. Among these enzymes, a protease isolated from Aspergillus oryzae showed the highest angiotensin-I converting enzyme inhibitory activity per peptide. The A. oryzae peptide also showed the highest antihypertensive effect in spontaneously hypertensive rats when the systolic blood pressure was measured 5 h after oral administration of 32 mg/kg of various enzymatic hydrolysates. Significant antihypertensive effects were observed with dosages of 9.6, 32, and 96 mg of the A. oryzae peptide/kg of body weight (BW), and the effects were dependent on these peptide dosages.Analysis of peptide length showed the A. oryzae hydrolysate was the shortest of all tested casein hydrolysates; the peptide mixture had an average value of 1.4 amino acids (AA) in the sequence. To further characterize the A. oryzae hydrolysate, we analyzed the AA sequence of the whole peptide mixture. Various AA were detected at the first AA position, however, an increased number of Pro residues were observed at the second and third position of the A. oryzae hydrolysate. No strong signals were detected after the fourth AA position of the A. oryzae hydrolysate. These results suggest that the casein hydrolysate of A. oryzae, which expressed potent antihypertensive effects in spontaneously hypertensive rats, mainly contain short peptides of X-Pro and X-Pro-Pro sequences.     

Contrasting effects of water-soluble and water-insoluble dietary fibers on bile acid conjugation and taurine metabolism in the rat

The effect of the type of dietary fiber on the bile acid and taurine metabolism was examined in rats. Diets containing 10% of various water-soluble fibers (citrus pectin, konjak mannan, guar gum) as compared to a fiber-free diet increased biliary excretion of total bile acids. In contrast, water-insoluble dietary fibers (cellulose, corn bran, chitin; 10% in the diets) as well as cholestyramine (5% in the diet) considerably, decreased bile acid excretion. Water-soluble dietary fibermediated increases in bile acid excretion were totally attributable to increases in glycine-conjugates. Thus, these fibers greatly increased by the bile acid glycine-to-taurine ratio (G/T). Excretio of glycine conjugates decreased more than that of taurine conjugates in rats fed various water-insoluble dietary fibers. As a results, G/T in rats fed water-insoluble fibers was significantly lowered as compared to G/T in animals fed a fiber-free diet. Cholestyramine did not affect the G/T ratio of bile acids. Fecal bile acid excretion and the activities of hepatic cholesterol 7α-hydroxylase (EC 1.14.13.17) in rats fed various water-soluble dietary fibers approximately doubled as compared to the respective values for rats fed a fiber-free diet. Whereas cholestyramine greatly increased these parameters, water-insoluble fibers did not significantly affect them. Various water-soluble fibers decreased hepatic concentration and urinary excretion of taurine as well as the activity of hepatic cysteine dioxygenase (EC 1.13.11.20). In contrast, water-insoluble fibers considerably increased hepatic taurine concentrations and enzyme activities. The parameters for taurine metabolism were unaffected by cholestyramine. It was suggested that the types of dietary fiber affected hepatic taurine synthesis and thus modified bile acid glycine/taurine ratios.     

Mouse Gastric Epithelial Cells Resist CagA Delivery by the Helicobacter pylori Type IV Secretion System

The initial step in bacterial infection is adherence of the bacterium to the target cell surface. Helicobacter pylori exploits the interaction of bacterial adhesin protein HopQ with human epithelial CEACAMs (CEACAM1, 5, and 6) to stably adhere to gastric epithelial cells, which is necessary for delivery of the H. pylori CagA oncoprotein into the epithelial cells via a type IV secretion system. In contrast to human CEACAMs, however, HopQ does not interact with Ceacam1 (mouse CEACAM1) in vitro or in CHO cells ectopically expressing Ceacam1. Since the mouse genome lacks Ceacam5 and Ceacam6, no significant HopQ–Ceacam interaction may occur in mouse gastric epithelial cells. Here, we found that the mouse stomach has a much lower expression level of Ceacam1 than the expression level of CEACAM1 in the human stomach. Consistently, mouse gastric epithelial cells resist CagA delivery by cagA-positive H. pylori, and the delivery is restored by ectopic expression of human CEACAM1 or CEACAM5 in mouse gastric epithelial cells. Thus, despite the fact that mice are routinely used for H. pylori infection studies, a low expression level of Ceacam1 in the mouse stomach together with the loss or greatly reduced interaction of HopQ with Ceacams make the mouse an inappropriate model for studying the role of H. pylori-delivered CagA in gastric pathogenesis, including the development of gastric cancer.     

Reactive ion etching of PECVD silicon nitride in SF6 plasma

The reactive ion etching of PECVD silicon nitride thin films has been investigated using SF₆ plasma. Effects of variations of process parameters such as pressure (50–350 mTorr), RF power (50–250 W), gas flow rate (3–130 sccm) and additions of O₂ and He (0–50%) in SF₆, on the PECVD silicon nitride etch rate and selectivity to the AZ 1350J photoresist were examined. An etch rate of 1 μm/min has been obtained under the condition of 150 mTorr, 100 W and 60 sccm. Experimental results also indicated a maximum etch rate at approximately 30% O₂ while addition of He showed only dilution effect. A nitride/photoresist selectivity ranging from 1 to 3:1 has been obtained.     

Effect of gamma radiolysis on pit initiation of zircaloy-2 in water containing sea salt

In spent fuel pools at the Fukushima Daiichi Nuclear Power Station (1F), seawater was injected for cooling purposes after the tsunami disaster in March 2011. It is well known that the chloride in the seawater has the potential to cause localized corrosion (e.g., pitting corrosion) in metals. In this study, we evaluated the pitting potentials of zircaloy-2, the material used in the fuel cladding tubes in 1F, as a function of chloride concentration. To accomplish this, we used artificial seawater under gamma-ray irradiation and investigated the effect of radiolysis on pit initiation of zircaloy-2 in water containing sea salt. Changes in the composition of water containing sea salt were analyzed as well, both before and after gamma-ray irradiation. The characteristics of the resultant oxide films formed on zircaloy-2 were evaluated by X-ray photoelectron spectroscopy and electrochemical impedance spectroscopy. The experimental results showed that the pitting potential under irradiation was slightly higher than that under conditions in which no radiation was present, and that the pitting potential decreased with increasing chloride concentration in the presence as well as the absence of radiation. Solution analyses for water containing sea salt showed that hydrogen peroxide was generated by irradiation. The oxide film was composed of zirconium oxide and was made thicker during the irradiation. The higher pitting potential could thus be explained by the capacity of hydrogen peroxide to oxidize the surface and enhance oxide film formation. Under gamma-ray irradiation, the zircaloy-2 surface with an oxide film formed by radiolysis products was found to be resistant to pitting in the presence of chloride.     

Examination of pin-by-pin fission rate distribution in large geometry evaluated by the Monte-Carlo method

Accuracy and reliability of pin-by-pin fission rate distribution in large geometries calculated by the multi-group Monte-Carlo method is examined through comparison with a deterministic transport code based on the method of characteristics. Various calculation geometries from a single assembly to a PWR full core are used for comparison of pin-by-pin fission rate distribution. An integral parameter, i.e., k-effective, can be accurately calculated by the Monte-Carlo method with a practical number of neutron histories (10⁶–10⁷) regardless of the size of the calculation geometry. On the other hand, comparison with the deterministic calculation shows that the estimated statistical errors for pin-by-pin fission rate distribution obtained by a Monte-Carlo calculation are somewhat underestimated in a large geometry, e.g., a PWR full core, under the present calculation conditions. Such underestimation of the statistical uncertainty of a local parameter should be carefully considered when the Monte-Carlo method is used as a reference tool for verification of a deterministic code, especially in large geometries.