High-fat diet (HFD) could induce prostate cancer progression. The aim of this study is to identify mechanisms of HFD-induced prostate cancer progression, focusing on inflammation. We administered HFD and celecoxib to autochthonous immunocompetent Pb-Cre;(fl/fl) model mice for prostate cancer. Tumor growth was evaluated by tumor weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age. Cytokines which correlated with tumor growth were identified, and the changes of tumor growth and local immune cells after inhibition of the cytokine signals were evaluated in the mice. IHC analyses using prostatectomy specimens of obese patients were performed. HFD accelerated tumor growth and increased the myeloid-derived suppressor cells (MDSCs) fraction and M2/M1 macrophage ratio in the model mice. Celecoxib-suppressed tumor growth, and decreased both local MDSCs and M2/M1 macrophage ratio in HFD-fed mice. HFD-induced tumor growth was associated with IL6 secreted by prostatic macrophages, as were phosphorylated STAT3 (pSTAT3)-positive tumor cells. Anti-IL6 receptor antibody administration suppressed tumor growth, and decreased local MDSCs and pSTAT3-positive cell fractions in HFD-fed mice. The tumor-infiltrating CD11b-positive cell count was significantly higher in prostatectomy specimens of obese than those of nonobese patients with prostate cancer. HFD increased MDSCs and accelerated prostate cancer tumor growth via IL6/pSTAT3 signaling in the mice. This mechanism could exist in obese patients with prostate cancer. IL6-mediated inflammation could be a therapeutic target for prostate cancer. .

Reliable biomarkers for renal cell carcinoma (RCC) have yet to be determined. Circulating tumor DNA (ctDNA) is an emerging resource to detect and monitor molecular characteristics of various tumors. The present study aims to clarify the clinical utility of ctDNA for RCC. Fifty‐three patients histologically diagnosed with clear cell RCC were enrolled. Targeted sequencing was carried out using plasma cell‐free DNA (cfDNA) and tumor DNA. We applied droplet digital PCR (ddPCR) to validate detected mutations. cfDNA fragment size was also evaluated using a microfluidics‐based platform and sequencing. Proportion of cfDNA fragments was defined as the ratio of small (50‐166 bp) to large (167‐250 bp) cfDNA fragments. Association of mutant allele frequency of ctDNA with clinical course was analyzed. Prognostic potential was evaluated using log‐rank test. A total of 38 mutations across 16 (30%) patients were identified from cfDNA, including mutations in TP53 (n = 6) and VHL (n = 5), and median mutant allele frequency of ctDNA was 10%. We designed specific ddPCR probes for 11 mutations and detected the same mutations in both cfDNA and tumor DNA. Positive ctDNA was significantly associated with a higher proportion of cfDNA fragments (P = .033), indicating RCC patients with ctDNA had shorter fragment sizes of cfDNA. Interestingly, the changes of mutant allele frequency in ctDNA concurrently correlated with clinical course. Positive ctDNA and fragmentation of cfDNA were significantly associated with poor cancer‐specific survival (P < .001, P = .011). In conclusion, our study shows the clinical utility of ctDNA status and cfDNA fragment size as biomarkers for prognosis and disease monitoring in RCC.

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BackgroundReliable biomarkers for renal cell carcinoma (RCC) have yet to be found. Circulating cell-free DNA (cfDNA) is an emerging resource for the diagnosis and prognosis of various cancers. This study aims to identify novel blood biomarkers for RCC.Materials And MethodsPlasma cfDNA was extracted from RCC patients (n = 92) and healthy controls (n = 41). Levels of cfDNA were determined using quantitative real-time PCR of ACTB as the target gene, and cfDNA fragment size was measured using a microfluidics-based platform. Diagnostic potential was assessed using receiver operating characteristic (ROC) and logistic regression analysis, and prognostic potential was evaluated using log-rank test.ResultsMedian levels of cfDNA from RCC patients were significantly higher than those from healthy controls (3803 vs 2242 copies/ml, p < 0.001). Median fragment sizes of cfDNA in RCC patients were shorter than those in healthy controls (170 vs 171 bp, p = 0.052). To evaluate level of cfDNA as a diagnostic tool for RCC, ROC curve analysis revealed a sensitivity of 63.0% and a specificity of 78.1%. Multivariate analysis indicated that age, gender and the level of cfDNA were significantly associated with the presence of RCC (p < 0.001, p = 0.013, p < 0.001, respectively). Additionally, shorter cfDNA fragment size was negatively associated with progression-free survival (p = 0.006).ConclusionsOur study demonstrates the diagnostic and prognostic potential of plasma cfDNA as a biomarker for RCC.

[1] Temporal and spatial variations in anthropogenic water vapor (AWV) emissions and anthropogenic heat (AH) in Tokyo were estimated using data from a geographic information system (GIS) and an energy-consumption database. The maximum value of AWV exceeded 500 W m À2 in summer in central Tokyo. Estimations of AWV were validated with field-measured data. The estimated and measured data agreed well, indicating that anthropogenic sources such as district cooling systems release large amounts of water vapor into the atmosphere.