Monocytes and macrophages are major components of the tumor microenvironment, but their contributions to human cancer are poorly understood. We used molecular profiling combined with functional assays to investigate the role of these cells in human renal cell carcinoma (RCC). Blood monocytes from RCC patients displayed a tumor-promoting transcriptional profile that supported functions like angiogenesis and invasion. Induction of this protumor phenotype required an interleukin-1 receptor (IL-1R)-dependent mechanism. Indeed, targeting of IL-1-IL-1R axis in a human RCC xenograft model abrogated the protumor phenotype of tumor-associated macrophages (TAMs) and reduced tumor growth in vivo. Supporting this, meta-analysis of gene expression from human RCC tumors showed IL1B expression to correlate with myelomonocytic markers, protumor genes, and tumor staging. Analyzing RCC patient tumors confirmed the protumor phenotype of TAMs. These data provide direct evidence for a tumor-promoting role of monocytes and macrophages in human cancer and indicate IL-1-IL-1R as a possible therapeutic target.
Recurrent acute uncomplicated urinary tract infection has a negative impact on the quality of life of premenopausal, otherwise healthy women. Recurrent acute uncomplicated urinary tract infection patients who also have chronic constipation or consume caffeine have lower quality of life than those who do not. More studies are required to understand the relationships between these common problems and risk factors.
Objectives
To investigate plasma and urinary kynurenine (KYN)–tryptophan (TRP) ratios in bladder cancer, expression of indoleamine 2,3‐dioxygenase 1 (IDO1) in relation to tryptophan 2,3‐dioxygenase (TDO2) in bladder tumour, and the correlation of KYN–TRP ratio with bladder tumour burden.
Methods
Metabotyping of the TRP–KYN metabolic axis was performed via a clinical case–control study. Expression of IDO1 and TDO2 was measured in human biopsied tissues. Correlational experiments between KYN–TRP ratio and bladder tumour were performed using a murine orthotopic prostate‐specific antigen (PSA)‐secreting MB49 bladder cancer model.
Results
We established for the first time that plasma TRP level was significantly decreased, while both plasma and urinary KYN–TRP ratios were significantly higher in bladder cancer patients, and expression level of IDO1 but not TDO2 was increased in human bladder tumour. We reported the positive correlation between IDO1 expression, KYN–TRP ratio, normalized PSA to creatinine, and bladder tumour burden in the murine model.
Conclusion
Kynurenine–tryptophan ratio is a promising surveillance biomarker for bladder cancer, but would require further validation before clinical translation.
Kidney Disease Outcomes Quality Initiative stage 3 chronic kidney disease or worse occurs in 24.4% of kidney donors. Long-term prospective studies and closer followup of donors are needed to identify its implications, given the associated risk of cardiovascular diseases with chronic kidney disease in the general population.
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