With recent advancements in a non-invasive approach to cancer diagnosis and surveillance, the term “liquid biopsy” has gained traction but is currently limited by technological challenges in identifying and isolating circulating tumor cells (CTCs), proteins, cell-free DNA (cfDNA), or other nucleic acids. Tumor tissue biopsy, especially in genitourinary (GU) system is sometimes inadequate and requires invasive surgical options, especially for upper tract urothelial cancer. Urine can prove to be “liquid gold” since it may be a more abundant source of tumor-derived material without the background noise; however, urine DNA (uDNA) may be associated with low mutant allele fraction (MAF). Molecular detection of mutations in uDNA requires a sensitive and accurate method of analysis that allows a high depth of sequencing while minimizing artifacts. Several sequencing approaches to address this hurdle using enhanced library preparation techniques such as Tagged amplicon deep sequencing (TAm-Seq), Safe-SeqS, FAST-SeqS, and CAPP-Seq approaches have been developed. Urine biopsy utilizing next-generation sequencing (NGS) can prove useful at all stages of urologic malignancy care, where urine can be collected to aid in clinical decision making through the identification of commonly known mutations, and potentially reduce or avoid all forms of invasive procedures.

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Purpose of the review: The purpose of this review is to examine evaluate similarities and differences in bladder cancer expression subtypes and to understand the clinical implications of the molecular subtyping.Recent Findings: Four independent classification systems have been described, and there are broad similarities among the subtyping callers. Two major subtypes have been identified i.e. luminal and basal, with underlying subcategories based on various distinct characteristics. Luminal tumors generally bear a better prognosis and increased survival than basal tumors, although there is subtle variation in prognosis among the different subtypes within the luminal and basal classifications. Clinical subtyping is now commercially-available, although there are limitations to its generalizability and application.Summary: Expression subtyping is a new method to personalize bladder cancer management. However, there is probably not sufficient evidence to incorporate use into current standards-ofcare. Validation cohorts with clinically meaningful outcomes may further establish the clinical relevance of molecular subtyping of bladder cancer. Additionally, genetic alterations in bladder cancer may 'color' the interpretation of individual tumors beyond the expression subtype to truly personalize care for bladder cancer.

This article presents the synthesis, self-assembly, and biological activity as transfection agents for pDNA, siRNA, and mRNA of novel pyridinium pseudogemini surfactants, interfacially engineered from the most efficient gemini surfactants and lipids generated in our amphiphile research program. Formulation of novel amphiphiles in water revealed supramolecular properties very similar to those of gemini surfactants, despite their lipidlike charge/mass ratio. This dual character was found also to enhance endosomal escape and significantly increase the transfection efficiency. We were also successful in identifying the parameters governing the efficient delivery of pDNA, siRNA, and mRNA, drawing valuable structure-activity and structure-property relationships for each nucleic acid type, and establishing DNA/siRNA/mRNA comparisons. Several supramolecular complexes identified in this study proved to be extremely efficient nucleic acid delivery systems, displaying excellent serum stability and tissue penetration in three-dimensional organoids.

Imidazolium salts have shown great promise as anticancer materials. A new imidazolium salt (TPP1), with a triphenylphosphonium substituent, has been synthesized and evaluated for in vitro and in vivo cytotoxicity against bladder cancer. TPP1 was determined to have a GI 50 ranging from 200 to 250 μM over a period of 1 h and the ability to effectively inhibit bladder cancer. TPP1 induces apoptosis, and it appears to act as a direct mitochondrial toxin. TPP1 was applied intravesically to a bladder cancer mouse model based on the carcinogen N-butyl-N-(4hydroxybutyl)nitrosamine (BBN). Cancer selectivity of TPP1 was demonstrated, as BBN-induced tumors exhibited apoptosis but normal adjacent urothelium did not. These results suggest that TPP1 may be a promising intravesical agent for the treatment of bladder cancer.

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Mouse CXCL14/BRAK is a monocyte-selective chemokine which is expressed in almost all normal tissues. A flood of reports on its new functions of tumor suppression and fat metabolism modulation has left CXCL14 a potential therapeutic candidate for these diseases. Therefore, a simple accessible method is on demand for large-scale production of recombinant mouse CXCL14 protein for in vivo animal studies. Here, we introduce an efficient method for large-scale production of recombinant mouse CXCL14, by which an 18-mg protein is produced from 2-L Escherichia coli culture with good bioactivity and low level of endotoxin.

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