Burden of Prostate Cancer in China, 1990-2019: Findings From the 2019 Global Burden of Disease Study.
Frontiers in endocrinology
Our study is the first to illustrate the age and geographic distribution differences in the epidemiology of prostate cancer from 1990 to 2019 in China. Prostate cancer (PC) is a malignant tumor derived from prostate epithelial cells and is one of the most commonly diagnosed cancers in men. In recent years, the global incidence and the annual deaths number of PC showed a continuous increase, which has caused a huge disease burden on human health. In terms of the global average, the incidence and mortality of PC in China are relatively low. However, the age-standardized incidence rate of PC was 17.3/100,000 in 2019 in China, with a 95.2% rise compared to 1990, while the global growth rate of incidence rate over the same period is 13.2%. This showed that the development trend of PC in China is not optimistic. There are few precise studies on the epidemiology of PC in China. After the general analysis strategy used in the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019, we elaborated on the incidence, mortality, and disability-adjusted life-years (DALYs) and the corresponding age-standardized rate of the Chinese PC population from 1990 to 2019 according to different ages and provinces. We used joinpoint regression analysis to estimate the incidence and mortality trends. Our analysis shows that elderly people over 80 are still the main focus of incidence and death. The epidemiology and disease burden of PC of different provinces in China show obvious regional differences, and some certain provinces such as HongKong, Macao, and Zhejiang should be paid more attention. More targeted and effective strategies should be developed to reduce the burden of PC in China.
Regulation of STATs by polycystin-1 and their role in polycystic kidney disease.
Weimbs Thomas,Olsan Erin E,Talbot Jeffrey J
Autosomal-dominant polycystic kidney disease (ADPKD) is a common genetic disease caused by mutations in the gene coding for polycystin-1 (PC1). PC1 can regulate STAT transcription factors by a novel, dual mechanism. STAT3 and STAT6 are aberrantly activated in renal cysts. Genetic and pharmacological approaches to inhibit STAT3 or STAT6 have led to promising results in ADPKD mouse models. Here, we review current findings that lead to a model of PC1 as a key regulator of STAT signaling in renal tubule cells. We discuss how PC1 may orchestrate appropriate epithelial responses to renal injury, and how this system may lead to aberrant STAT activation in ADPKD thereby causing inappropriate activation of tissue repair programs that culminate in renal cyst growth and fibrosis.
Renal expression of JAK2 is high in polycystic kidney disease and its inhibition reduces cystogenesis.
Patera Foteini,Cudzich-Madry Alex,Huang Zhi,Fragiadaki Maria
Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal genetic disorder, however it still lacks a cure. The discovery of new therapies heavily depends on understanding key signalling pathways that lead to ADPKD. The JAnus Kinase and Signal Transducers and Activators of Transcription (JAK/STAT) pathway is aberrantly activated and contributes to ADPKD pathogenesis via enhancing epithelial proliferation. Yet the mechanisms underlying the upregulation of JAK/STAT activity in this disease context is completely unknown. Here, we investigate the role of JAK2 in ADPKD using a murine model of ADPKD (Pkd1). In normal kidneys, JAK2 expression is limited to tubular epithelial and vascular cells with lesser staining in bowman's capsule and remains below detection level in the interstitium. By contrast, in kidneys of mice with ADPKD, JAK2 is higher in cyst-lining cells when compared to normal tubules and critically, it is ectopically expressed in the interstitium, suggesting that ectopic JAK2 may contribute to ADPKD. JAK2 activity was inhibited using either curcumin, a natural compound with strong JAK2 inhibitor activity, or Tofacitinib, a clinically used selective JAK small molecule inhibitor. JAK2 inhibition led to significantly reduced tyrosine phosphorylation of STAT3 and markedly reduced cystic growth of human and mouse ADPKD-derived cells in cystogenesis assays. Taken together, our results indicate that blockade of JAK2 shows promise as a novel therapeutic target in ADPKD.