Immunohistochemistry of the human normal adrenal cortex for CYP11B2 and CYP11B1 revealed a variegated zonation with cell clusters constitutively expressing CYP11B2. This technique may provide a pathological confirmatory diagnosis of adrenocortical adenomas.

Neuroendocrine prostate cancer (NEPC) is an aggressive malignancy with no effective targeted therapies. The oncogenic MUC1-C protein is overexpressed in castration-resistant prostate cancer (CRPC) and NEPC, but its specific role is unknown. Here, we demonstrate that upregulation of MUC1-C in androgen-dependent PC cells suppresses androgen receptor (AR) axis signaling and induces the neural BRN2 transcription factor. MUC1-C activates a MYC→BRN2 pathway in association with induction of MYCN, EZH2 and NE differentiation markers (ASCL1, AURKA and SYP) linked to NEPC progression. Moreover, MUC1-C suppresses the p53 pathway, induces the Yamanaka pluripotency factors (OCT4, SOX2, KLF4 and MYC) and drives stemness. Targeting MUC1-C decreases PC self-renewal capacity and tumorigenicity, suggesting a potential therapeutic approach for CRPC and NEPC. In PC tissues, MUC1 expression associates with suppression of AR signaling and increases in BRN2 expression and NEPC score. These results highlight MUC1-C as a master effector of lineage plasticity driving progression to NEPC.

Candesartan exerted preventive effects on HRPC, rather than on androgen-sensitive PCa, through the inhibition of tumor angiogenesis.

Tumor necrosis factor-a (TNF-a) is involved in epithelial-mesenchymal transition (EMT) and expression of CD44, a cancer stem cell marker, in several cancers. This study was performed to clarify the significance of TNF-a and CD44 in clear cell renal cell carcinomas (ccRCCs). Expression of TNF-a and CD44 was examined by immunohistochemistry in 120 ccRCCs. Involvement of TNF-a in EMT and induction of CD44 was analyzed by monitoring expression of EMT-related genes and CD44, and invasion in cultured ccRCC cell lines. TNF-a and CD44 were immunolocalized mainly to carcinoma cells of high-grade ccRCCs with positive correlations with primary tumor stage. A positive correlation was also obtained between TNF-a and CD44 expression, and co-upregulation of TNF-a and CD44 was associated with primary tumor stage, distant metastasis, and poor prognosis. TNF-a enhanced migration and invasion of ccRCC cells together with down-regulation of E-cadherin expression and up-regulation of matrix metalloproteinase 9 and CD44 expression. TNF-a also up-regulated the expression of TNF-a itself in ccRCC cells. Among the 25 ccRCC patients treated with sunitinib for metastatic disease, high CD44 expression was associated with poor treatment outcome. Importantly, residual carcinoma cells in the sunitinib-treated metastatic ccRCCs were strongly positive for CD44, and the CD44 expression was significantly higher in the tumors from the sunitinib-treated patients than in those from untreated ones. Our data show that TNF-a plays an important role in progression of ccRCCs by inducing EMT and CD44 expression, and suggest that CD44 induced by TNF-a may be involved in the resistance to the sunitinib treatment.Cancer-related inflammation accelerates tumor cell proliferation and angiogenesis.1 Tumor necrosis factor-a (TNF-a) is an important mediator for the inflammatory responses in cancers, and infiltrated macrophages are a major source of TNF-a.2 Although TNF-a was originally reported as a cytokine to induce apoptotic cell death and cachexia, 1 accumulated lines of evidence indicate that TNF-a has tumorpromoting effects. 2 Actually, TNF-a produced by tumor cells is known to induce tumor cell proliferation and progression by autocrine and paracrine manners in ovarian cancers, 3 and TNF-a enhances epithelial-mesenchymal transition (EMT) of clear cell renal cell carcinoma (ccRCC) cells in vitro.4 TNF-a

The Min mouse, which has a germ line mutation in 1 allele of the Apc tumor suppressor gene, is a model for the early steps in human colorectal cancer. Helicobacter pylori infection, a known risk factor for gastric cancer in humans, causes chronic inflammation and increased epithelial cell proliferation in the stomach. Infection with the bacterium Citrobacter rodentium is known to increase epithelial cell proliferation and to promote chemically initiated tumors in the colon of mice. Min mice infected with C. rodentium at 1 month of age were found to have a 4-fold increase in the number of colonic adenomas at 6 months of age, compared with uninfected Min mice. Most of the colonic adenomas in the infected Min mice were in the distal colon, where C. rodentium-induced hyperplasia occurs. These data demonstrate that bacterial infection promotes colon tumor formation in genetically susceptible mice.