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The human six-transmembrane epithelial antigen of the prostate (STEAP) proteins, which include STEAP1–4 and atypical STEAP1B, contain six transmembrane domains and are located in the cell membrane. STEAPs are considered archaeal metal oxidoreductases, based on their heme groups and F420H2:NADP+ oxidoreductase (FNO)-like structures, and play an important role in cell metal metabolism. Interestingly, STEAPs not only participate in biological processes, such as molecular transport, cell cycling, immune response, and intracellular and extracellular activities, but also are closely related to the occurrence and development of several diseases, especially malignant tumors. Up to now, the expression patterns of STEAPs have been found to be diverse in different types of tumors, with controversial participation in different aspects of malignancy, such as cell proliferation, migration, invasion, apoptosis, and therapeutic resistance. It is clinically important to explore the potential roles of STEAPs as new immunotherapeutic targets for the treatment of different malignant tumors. Therefore, this review focuses on the molecular mechanism and function of STEAPs in the occurrence and development of different cancers in order to understand the role of STEAPs in cancer and provide a new theoretical basis for the treatment of diverse cancers.

BackgroundAngiogenesis plays critical roles in the progression and metastasis of malignant tumors. Gastric neuroendocrine carcinoma is an uncommon stomach cancer that is rich in blood vessels and exhibits highly malignant biological behavior with a poor prognosis. The role of CDK5RAP3 in GNEC has not been reported to date.MethodsImmunohistochemistry was used to assess the expression of CDK5RAP3 in GNEC tissues and adjacent non-tumor tissues. Cell lines with stable overexpression or knockdown of CDK5RAP3 were constructed using lentiviral transfection. Wound-healing assays, invasion and metastasis assays, tube formation assays, and tumor xenograft transplantation assays were performed to evaluate the effect of CDK5RAP3 on GNEC angiogenesis in vitro and in vivo. Real-time PCR, ELISA, western blot analysis, and confocal-immunofluorescence staining were used to explore the molecular mechanism of CDK5RAP3′s effect on angiogenesis.ResultsCompared with their respective adjacent non-tumor tissues, protein levels of CDK5RAP3 were significantly decreased in GNEC tissues. Furthermore, low expression of CDK5RAP3 was correlated with more advanced TNM stage, increased tumor microvessel density, and poor prognosis. Functionally, we found that GNEC cells with CDK5RAP3 knockdown promoted human umbilical vein endothelial cells migration and tube formation via activation of AKT/HIF-1α/VEGFA signaling, resulting in increased levels of VEGFA in GNEC cell supernatant. In addition, CDK5RAP3 overexpression in GNEC cells caused the opposing effect. Consistent with these results, nude mouse tumorigenicity assays showed that CDK5RAP3 expression downregulated angiogenesis in vivo. Lastly, patients with low CDK5RAP3 expression and high VEGFA expression exhibited the worst prognosis.ConclusionsThis study demonstrated that CDK5RAP3 inhibits angiogenesis by downregulating AKT/HIF-1α/VEGFA signaling in GNEC and improves patient prognosis, suggesting that CDK5RAP3 could be a potential therapeutic target for GNEC.

Chlorogenic acid (CGA) is a natural compound with many important pharmacological effects including anti-hypertension. This study aimed to investigate the anti-hypertensive effect of CGA on high-fructose-induced salt-sensitive hypertension and the...

Abstract. Surgical biopsy is a method for diagnosing breast cancer. The aim of this study was to prospectively evaluate the relative accuracies of mammography (MMG) and ultrasound (US) in predicting residual disease following bioptic lumpectomy. Each prediction method was compared with the gold standard of surgical pathology. The results of MMG and US from 312 consecutive breast cancer patients diagnosed by surgical excision were analyzed. All the patients underwent re-excision mastectomy or lumpectomy and the imaging results were compared with the histopathological findings. The accuracy and sensitivity of each modality were investigated. A total of 312 patients with 312 primary breast cancers were investigated. Residual disease was identified in 118 patients. Of the 118 cases with residual disease, MMG and US were able to detect 77 (65.3%) and 32 (27.1%), respectively (Chi-square P<0.001). MMG was also more sensitive compared with US in estimating residual ductal carcinoma in situ (DCIS) (94.2 vs. 33.3%, respectively; P<0.001). MMG was more accurate compared with US in detecting residual disease following bioptic lumpectomy and the diagnostic accuracy of MMG was associated with the presence of residual DCIS.