Treatment of metastatic disease remains among the most challenging tasks in oncology. One of the early events that predicts a poor prognosis and precedes the development of metastasis is the occurrence of clusters of cancer cells in the blood flow. Moreover, the presence of heterogeneous clusters of cancerous and noncancerous cells in the circulation is even more dangerous. Review of pathological mechanisms and biological molecules directly involved in the formation and pathogenesis of the heterotypic circulating tumor cell (CTC) clusters revealed their common properties, which include increased adhesiveness, combined epithelial-mesenchymal phenotype, CTC-white blood cell interaction, and polyploidy. Several molecules involved in the heterotypic CTC interactions and their metastatic properties, including IL6R, CXCR4 and EPCAM, are targets of approved or experimental anticancer drugs. Accordingly, analysis of patient survival data from the published literature and public datasets revealed that the expression of several molecules affecting the formation of CTC clusters predicts patient survival in multiple cancer types. Thus, targeting of molecules involved in CTC heterotypic interactions might be a valuable strategy for the treatment of metastatic cancers.
High toxicity and huge foaming are two severe challenges for gas storage strategies based on promoting the gas hydrate formation using surfactants. The present study used castor oil as an eco-friendly resource to develop novel biosurfactants for methane storage. Transmission and scanning electron microscopy, dynamic light scattering, and interfacial tension measurements revealed the surfactant properties of sulfonated castor oil (SCO). In addition, a high-pressure autoclave and a microdifferential scanning calorimeter test unveiled SCO as an effective kinetic hydrate promoter. The results showed that SCO significantly enhanced the rate of methane hydrate formation. A maximum of 76% water-tohydrate conversion was observed in 0.1 wt % SCO solution under stirring conditions. Pure water, 0.1 wt % SCO, and 0.1 wt % sodium dodecyl sulfate (SDS) solutions allowed 50% conversion to be achieved for 329, 39, and 27 min, respectively. This made the castor oil-based reagent as effective as the well-known kinetic hydrate promoter SDS. Furthermore, the SCO solution's foam ratio and stability were 8.25 and 2.75 times lower than those of SDS. Additionally, SCO showed a more favorable safety profile for humans and the environment as it is toxic to animals in higher concentrations than SDS according to in vivo studies. In addition, a combination of high-pressure DSC, low-temperature powder Xray diffractometry, and visual analysis of hydrate samples depending on the temperature mode, promoter type, and its concentration revealed that SCO and SDS enhanced hydrate growth by different mechanisms. The loose hydrate mass was squeezed out toward the gas phase in both cases. However, in the case of SDS, the hydrate traditionally climbed the cell walls while SCO seemed to change the wall wettability, which led to the transfer of water into the reaction zone along with the forming hydrate crystals and the domed shape of the hydrate. These findings provide reliable evidence to synthesize efficient and environmentally friendly reagents based on castor oil to improve methane storage in the clathrate hydrate.
Mechanistically, chimeric genes result from DNA rearrangements and include parts of preexisting normal genes combined at the genomic junction site. Some rearranged genes encode pathological proteins with altered molecular functions. Those which can aberrantly promote carcinogenesis are called fusion oncogenes. Their formation is not a rare event in human cancers, and many of them were documented in numerous study reports and in specific databases. They may have various molecular peculiarities like increased stability of an oncogenic part, self-activation of tyrosine kinase receptor moiety, and altered transcriptional regulation activities. Currently, tens of low molecular mass inhibitors are approved in cancers as the drugs targeting receptor tyrosine kinase (RTK) oncogenic fusion proteins, that is, including ALK, ABL, EGFR, FGFR1-3, NTRK1-3, MET, RET, ROS1 moieties. Therein, the presence of the respective RTK fusion in the cancer genome is the diagnostic biomarker for drug prescription. However, identification of such fusion oncogenes is challenging as the breakpoint may arise in multiple sites within the gene, and the exact fusion partner is generally unknown. There is no gold standard method for RTK fusion detection, and many alternative experimental techniques are employed nowadays to solve this issue. Among them, RNA-seq-based methods offer an advantage of unbiased high-throughput analysis of only transcribed RTK fusion genes, and of simultaneous finding both fusion partners in a single RNA-seq read. Here we focus on current knowledge of biology and clinical aspects of RTK fusion genes, related databases, and laboratory detection methods.
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