Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug's reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity

Microstructure and thermal conductivities of suspension vacuum plasma sprayed YSZ coatings

To increase the efficiency of gas turbine, the turbine inlet temperature should increase. As the turbine inlet temperature increases, the heat load of thermal barrier coating increases. Suspension plasma spraying(SPS) was developed to enhance the performance of thermal barrier coating. Suspension allows nano-sized powders to be injected into the plasma flame, which has advantage of forming a variety of microstructures. However, there is a disadvantage of SPS that cannot be completely transmitted the enthalpy of plasma flame due to evaporation of solvent in the suspension, which causes decrement of coating formation rate. In this study, disadvantages of the suspension atmospheric plasma spraying(SAPS) can be solved by forming YSZ coatings through suspension vacuum plasma spraying(SVPS). The length of plasma flame in vacuum condition becomes longer, powders can stay longer inside the plasma flame. A variety of microstructured YSZ coatings were formed by SPVS at various spraying conditions. Microstructure of SVPS YSZ coatings were analyzed by SEM. Thermal conductivity of SVPS YSZ coatings were analyzed by laser flash method. Coating formation rate showe

Production of Reducing Sugars from Laminaria japonica by Subcritical Water Hydrolysis

AbstractThis study was to investigate the production of reducing sugars in hydrolysates from raw and deoiled Laminaria japonica produced by subcritical water hydrolysis. Deoiled Laminaria japonica was collected by supercritical carbon dioxide (SCO2) extraction process. Experiments were performed in a batch-type reactor with stirring. It investigated that the effects of reaction temperature and acetic acid as catalyst on content of reducing sugar production. The addition of acetic acid led to an increase in content of reducing sugar. But Removal of oil in Laminaria japonica by SCO2 and increasing of temperature led to decrease in content of reducing sugar production. The highest content of reducing sugar was 814.10mg/100g raw dried sample at 200°C, adding of 1% acetic acid as catalyst

Current Status of Biportal Endoscopic Decompression for Lumbar Foraminal Stenosis: Endoscopic Partial Facetectomy and Outcome Factors

Degenerative lumbar foraminal stenosis is relatively common condition in which the circumferential narrowing of the space available for the nerve root leads to back pain and radicular symptoms. The preferred surgical treatment to relieve the compression of the nerve root has not been established yet. Recently, several reports have shown good clinical outcomes in patients who underwent biportal endoscopic decompression for the treatment of degenerative lumbar foraminal stenosis. The floating-type biportal endoscopic technique could be used with various surgical instruments without docking in the narrowed foramen, unlike the full-endoscopic technique. Multiple sites can be accessed with more freedom in the approaching angle through triangulation and portal switching. We reviewed articles to understand putative outcome factors and discuss the appropriate indications for biportal endoscopic foraminal decompression. Lumbar lordosis, degenerative lumbar scoliosis, height of the posterior intervertebral disc and level of procedure were all related to clinical outcomes. The best indications and contraindications to the endoscopic foraminal decompression still depends on the surgeon’s skill level and evolving experience. However, we could suggest that biportal endoscopic spinal surgery is supposed to be an alternative treatment for foraminal decompression preserving motion and stability, and decreasing the need for fusion surgery in various lumbar degenerative disease

Thymic Metastasis in Breast Cancer: A Case Report

A malignant tumor is generally believed to be very unlikely to metastasize to the thymus. Only three cases of thymic metastases have been reported so far in the medical literature. We report here a rare case of metastatic breast cancer to the thymus, which was detected by CT and PET scanning, and the metastasis was also confirmed by video-assisted thoracic surgery biopsy. Recognition of an unusual breast cancer metastasis, such as to the thymus, as well as the usual patterns of breast cancer metastasis will facilitate an accurate, prompt diagnosis and its appropriate treatment