Therapeutic inhibition of SGK1 suppresses colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC.

Ultrasonic characteristics of peripheral arterial diseases and related risk factors in patients with end stage renal disease / 解放军医学杂志

Objective Peripheral arterial diseases(PAD)are most common conditions in patients with end stage renal disease(ESRD). However, PAD hasn′t been extensively studied like other cardiovascular or cerebrovascular diseases such as coronary heart disease and cerebral infarction among ESRD patients. The present study aims to investigate the ultrasonic characteristics of PAD and risk factors related to peripheral arterial intima thickening and plaques formation. Methods Seventy-three ESRD patients and 21 healthy individuals (as control) were involved in the investigation, and their carotid and lower-extremity arteries including tunica intima, lumen diameter, plaques and Doppler spectrums were examined with color Doppler ultrasonic technique. Then, the risk factors related to intima thickening and plaques formation among ESRD patients were studied combining with their clinical data and biochemical makers. Results The lesions of varying degrees in peripheral arteries occured in 52.1%(38/73) ESRD patients, including intima thickening, coarse and chaotic tunica intima, strong echo masses or atheromatous plaques with different shapes and sizes, widened and deformed Doppler spectrums, accelerated peak systolic velocity and lowered or disappeared diastolic reverse peak at narrow sites, low resistant blood flow at apo-stenosis sites (prolonged systolic accelerative time and decreased acceleration). The incidence of PAD was significantly higher in ESRD patients than that in control group (14.3%, P