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.     

Genetic Study of Four Candidate Holliday Junction Processing Proteins in the Thermophilic Crenarchaeon Sulfolobus acidocaldarius

Homologous recombination (HR) is thought to be important for the repair of stalled replication forks in hyperthermophilic archaea. Previous biochemical studies identified two branch migration helicases (Hjm and PINA) and two Holliday junction (HJ) resolvases (Hjc and Hje) as HJ-processing proteins; however, due to the lack of genetic evidence, it is still unclear whether these proteins are actually involved in HR in vivo and how their functional relation is associated with the process. To address the above questions, we constructed hjc-, hje-, hjm-, and pina single-knockout strains and double-knockout strains of the thermophilic crenarchaeon Sulfolobus acidocaldarius and characterized the mutant phenotypes. Notably, we succeeded in isolating the hjm- and/or pina-deleted strains, suggesting that the functions of Hjm and PINA are not essential for cellular growth in this archaeon, as they were previously thought to be essential. Growth retardation in Δpina was observed at low temperatures (cold sensitivity). When deletion of the HJ resolvase genes was combined, Δpina Δhjc and Δpina Δhje exhibited severe cold sensitivity. Δhjm exhibited severe sensitivity to interstrand crosslinkers, suggesting that Hjm is involved in repairing stalled replication forks, as previously demonstrated in euryarchaea. Our findings suggest that the function of PINA and HJ resolvases is functionally related at lower temperatures to support robust cellular growth, and Hjm is important for the repair of stalled replication forks in vivo.     

Sulfide oxidation by gene expressions of sulfide-quinone oxidoreductase and ubiquinone-8 biosynthase in Escherichia coli

Sulfides (S2),SH-) such as hydrogen sulfide belong to a class of sulfur compounds with unpleasant odors. In order to confer sulfide-oxidizing ability on the intestine-inhabiting bacteria, the sulfide-quinone oxidoreductase gene (sqr) in Rhodobacter capsulatus DSM-155 and genes for quinone biosynthesis (ubiC, ubiA and ispB) in Escherichia coli XL1 Blue-MRF' were transduced into E. coli BL21(DE3). Plasmids pT7-7 and pSTV were used as vectors of sqr, and ubiCA and ispB, respectively. The recombinants sqr-BL21(DE3) and ubiCA,ispB-sqr-BL21(DE3) were successfully constructed. The maximal sulfide-removing activities of the whole cells and membrane fractions of sqr-BL21(DE3) attained at pH 8.0 and 7.8, were 267 nmol/mg cells (dry weight)/min and 1250 nmol/mg membrane fraction (protein)/min, respectively. The molecular ratio of sulfide (S2-) oxidized and oxygen (O2) consumed was 2:1. SQR activity in the recombinant cells was positively restricted under anaerobic conditions and also by the addition of electron transfer inhibitors. Ubiquinone-8 (UQ-8) biosynthesis in the cells of ubiCA,ispB-sqr-BL21(DE3) increased as much as 2.2-fold compared with that of (pSTV)-sqr-BL21(DE3) during the 12-16 h incubation period. The maximal sulfide removal in the quinone-raised E. coli was attained slightly earlier, however, SQR activities thereafter were lower than those in (pSTV)-sqr-BL21(DE3).     

Alignment control of liquid crystals in a 1.0‐μm‐pitch spatial light modulator by lattice‐shaped dielectric wall structure

We achieved uniform liquid crystal (LC) alignment in lattice‐shaped dielectric walls 1 μm in pitch; this is a prerequisite when driving the individual pixels of spatial light modulators, facilitating the development of practical electronic holographic displays with a wide field of view. In lattice‐shaped dielectric walls, LC alignment becomes unstable, particularly on the bottom and the walls; the LC directors tend to align parallel to the walls. To overcome this problem, we created lattice‐shaped walls featuring partition plates that allow uniform LC alignment. When the plates confine LCs to small regions exhibiting spatial anisotropy, the LC elastic effect and wall anchoring forces align the LC directors parallel to the long anisotropic axis. We found that pixels 0.5 μm × 1.0 μm in pitch formed if the partition plates were sufficiently thick to allow shielding of electric field leakage.     

A quick and simple method for the identification of meat species and meat products by PCR assay

The polymerase chain reaction (PCR) was applied to identify six meats (cattle, pig, chicken, sheep, goat and horse) as raw materials for products. By mixing seven primers in appropriate ratios, species-specific DNA fragments could be identified by only one multiplex PCR. A forward primer was designed on a conserved DNA sequence in the mitochondrial cytochrome b gene, and reverse primers on species-specific DNA sequences for each species. PCR primers were designed to give different length fragments from the six meats. The products showed species-specific DNA fragments of 157, 227, 274, 331, 398 and 439 bp from goat, chicken, cattle, sheep, pig and horse meats, respectively. Identification is possible by electrophoresis of PCR products. Cattle, pig, chicken, sheep and goat fragments were amplified from cooked meat heated at 100 or 120°C for 30 min, but horse DNA fragments could not be detected from the 120°C sample. Detection limits of the DNA samples were 0.25 ng for all meats.     

The ex vivo effect of the herbal medicine sho-saiko-to on histamine release from rat mast cells

OBJECTIVE: This report describes subcutaneous sarcoidosis, focusing on the radiological and magnetic resonance (MR) features of the disease. DESIGN AND PATIENTS: The cases of four patients (one male and three female, age range 36-75 years) who had subcutaneous sarcoidosis with no other organs affected were reviewed. Lesions were nodular in two cases, and in the other two were diffuse. RESULTS: Computed tomography (CT) demonstrated a well-defined, homogeneous, and enhanced lesion in the nodular cases. However, in the diffuse cases, CT showed a heterogeneous, honeycomb-like appearance and little enhancement. Angiography showed a fine stain in the arterial phase. MR imaging of the nodular lesions was homogeneous with a signal intensity similar to muscle on T1-weighted images but heterogeneous with a higher signal than muscle on T2-weighted images. Diffuse lesions showed a striped or mesh pattern with intermediate signal intensity on both T1- and T2-weighted images. Contrast-enhanced MR images showed slight enhancement. CONCLUSIONS: Subcutaneous sarcoidosis should be considered in the differential diagnosis when a patient presents with the radiological and MR features described.     

Studies on synthetic-polymer plates with high surface energy. II. Diethylene glycol bis(allyl carbonate)–unsaturated carboxylic acid system

Polymer plates with high surface energy were prepared by the procedure described in the previous paper, using diethylene glycol bis(allyl carbonate) as a substrate polymer and acrylic acid or methacrylic acid as a hydrophilic monomer. By the alkali treatment (immersing in an aqueous 0.1N NaOH solution for 2 h), the resulting polymer plates had good water wettability (contact angle for water = 10°) and sufficient mar resistance (the scratching hardness = 45–50 g) in a dry state, and their clarities were higher than those for DAP systems previously reported. The surface densities of carboxyl groups on the polymer plate estimated by use of the McBain's equation were 0.18–0.46 molecule/Ų.     

Characterization of neurons differentiated from mouse embryonic stem cells using conditioned medium of dorsal root ganglia

Mouse embryonic stem (ES) cells have the pluripotent ability to differentiate in vitro into various cell lineages, including neurons. Adding chick dorsal root ganglion (DRG) conditioned medium (CM) to the culture medium promotes the differentiation of ES cells into neurons. We determined the types of neurons that differentiate from ES cells. The addition of DRG-CM caused nearly half of all ES cells on the periphery of the colony sphere to differentiate into neurons. Immunofluorescence analysis showed that the neurons that differentiated from ES cells were mainly motor, GABAergic, serotonergic, and cholinergic neurons. Of particular note, flow cytometry showed that approximately 50% of betaIII-tubulin-positive neurons were motor neurons. This indicates that DRG-CM induces ES cells to differentiate into motor neurons as target of DRG neurons (sensory neurons).     

A New Equation for Predicting the Dielectric Constant of a Mixture

The dielectric constant of a compound consisting of two different materials was simulated using the Monte Carlo and finite element methods. In the high concentration range of the higher dielectric constant material, the simulated value of the dielectric constant showed a "parallel-model"-like tendency. On the other hand, in the low concentration range of the higher dielectric constant material, the compound showed a "serial-model"-like behavior. Around 65% content of the higher dielectric constant material, it exhibited results similar to the logarithmic mixing rule. After careful consideration of these results, a new equation to predict the dielectric constant of the compound was derived. The agreement between the dielectric constant calculated by the new equation and the measured values was better than in any other case reported before.