Her2 alterations in muscle-invasive bladder cancer: Patient selection beyond protein expression for targeted therapy.

Although the introduction of novel targeted agents has improved patient outcomes in several human cancers, no such advance has been achieved in muscle-invasive bladder cancer (MIBC). However, recent sequencing efforts have begun to dissect the complex genomic landscape of MIBC, revealing distinct molecular subtypes and offering hope for implementation of targeted therapies. Her2 (ERBB2) is one of the most established therapeutic targets in breast and gastric cancer but agents targeting Her2 have not yet demonstrated anti-tumor activity in MIBC.

Does Stepwise Voltage Ramping Protect the Kidney from Injury During Extracorporeal Shockwave Lithotripsy? Results of a Prospective Randomized Trial.

Background: Renal damage is more frequent with new-generation lithotripters. However, animal studies suggest that voltage ramping minimizes the risk of complications following extracorporeal shock wave lithotripsy (SWL). In the clinical setting, the optimal voltage strategy remains unclear.

Bcl-2 predicts response to neoadjuvant chemotherapy and is overexpressed in lymph node metastases of urothelial cancer of the bladder.

Purpose: To assess whether Bcl-2, an inhibitor of the apoptotic cascade, can predict response to neoadjuvant chemotherapy in patients with urothelial cancer of the bladder (UCB).

Methods: Bcl-2 expression was analyzed in 2 different tissue microarrays (TMAs). One TMA was constructed of primary tumors and their corresponding lymph node (LN) metastases from 152 patients with chemotherapy-naive UCB treated by cystectomy and pelvic lymphadenectomy (chemotherapy-naive TMA cohort).

Toll-like receptor signaling and SIGIRR in renal fibrosis upon unilateral ureteral obstruction.

Innate immune activation via IL-1R or Toll-like receptors (TLR) contibutes to acute kidney injury but its role in tissue remodeling during chronic kidney disease is unclear. SIGIRR is an inhibitor of TLR-induced cytokine and chemokine expression in intrarenal immune cells, therefore, we hypothesized that Sigirr-deficiency would aggravate postobstructive renal fibrosis. The expression of TLRs as well as endogenous TLR agonists increased within six days after UUO in obstructed compared to unobstructed kidneys while SIGIRR itself was downregulated by day 10.

Quantitative expression of RIG-like helicase, NOD-like receptor and inflammasome-related mRNAs in humans and mice.

The cell-type-, organ- and species-specific expression of the surface and endosomally located Toll-like receptors are well described but little is known about the respective expression profiles of cytosolic pattern recognition molecules. We therefore determined the mRNA expression levels of 15 cytosolic pattern recognition molecules in 11 solid organs of human and mice. Human organs revealed lower mRNA levels of most molecules as in spleen but at least 2-fold higher were inflammasome-related NOD, leucine-rich repeat and pyrin domain-containing protein 1-3 (NLRP1-3) and -12 in brain, LGP2, retinoic acid-inducible gene I (RIG-I) and NLRP10 in liver, NLRP10 in small intestine, LGP2, RIG-I, NAIP, NLRP2 and -3 in testis and RIG-I, NLRP2 and -10 in muscle.

Lack of SIGIRR/TIR8 aggravates hydrocarbon oil-induced lupus nephritis.

Multiple genetic factors contribute to the clinical variability of spontaneous systemic lupus erythematosus (SLE) but their role in drug-induced SLE remain largely unknown. Hydrocarbon oil-induced SLE depends on mesothelial cell apoptosis and Toll-like receptor (TLR)-7-mediated induction of type I interferons. Hence, we hypothesized that TIR8/SIGIRR, an endogenous TLR inhibitor, prevents oil-induced SLE.