APAF-1 is related to an undifferentiated state in the testicular germ cell tumor pathway
Apoptotic protease activating factor-1 (APAF-1), a gene located downstream from the tumorsuppressor gene p53, is an important regulator of the apoptosis pathway. Previous studies have reported loss of APAF-1 expression in metastatic lesions and chemorefractory rectal tumors. Epigenetic inactivation of APAF-1 has been found in all seminomatous and non-seminomatous testicular germ cell tumors (TGCTs) in addition to 60% of normal testicular tissue. Furthermore, decreased APAF-1 has been associated with neuronal cell differentiation. In order to further elucidate the carcinogenic role of APAF-1 in germ cell tumors, Behjati and colleagues used immunohistochemistry to determine the expression levels of APAF-1 and several apoptosis and differentiation markers in both TGCT samples and normal testis tissue. The researchers found APAF-1 expression in the cytoplasm and cell membrane. APAF-1 levels did not significantly relate to markers of apoptosis; however, APAF-1 expression was correlated to markers of cell proliferation and undifferentiation. The authors suggest that APAF-1 is closely linked to an undifferentiated state in the TGCT pathway.
Spatial distribution of intraperitoneal injection of paclitaxel nanoparticles solubilized with poly (2-methacryloxyethyl phosphorylcholine-co n-butyl methacrylate) in peritoneal metastatic nodules
Most studies investigating systemic perfusion of anticancer drugs have reported limited efficacy in the treatment of peritoneal metastases. In contrast, i.p. injection of paclitaxel (PTX) has been clinically effective against peritoneal lesions in gastric and ovarian cancer. Although PTX is typically dissolved in Cremophor EL, Kamei and colleagues have previously reported that i.p. injection of nanoparticles containing PTX (PTX-30W) more effectively inhibited the growth of peritoneal metastases of gastric cancer. In this issue, the authors used fluorescence-labeled PTX-30W to compare the specific distribution of PTX-30W in peritoneal nodules and the liver following i.v. or i.p. injection. Intravenous injection led to greater PTX-30W accumulation in the liver than in peritoneal nodules, but i.p. injection led to greater drug accumulation in peritoneal tumor tissue, especially in hypovascular areas. The authors conclude that this unique accumulation pattern makes i.p. injection of PTX-30W an ideal therapeutic approach for peritoneal carcinomatosis.
Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility
A large body of evidence points to genetics playing a critical role in prostate cancer (PC) susceptibility. Recent genome-wide association studies have reported strong associations between PC and multiple genetic variants on a segment of chromosome 8q24. However, no gene has been identified within this segment, and the biological mechanisms of these susceptibility loci at 8q24 remain unclear. Focusing on the most centromeric region of the PC loci on 8q24, Chung and colleagues used fine-mapping and resequencing to identify single nucleotide polymorphisms most significantly associated with PC susceptibility. The researchers showed that this 8q24 region transcribed as a novel long non-coding RNA, PRNCR1. The expression of PRNCR1 was upregulated in PC cells and precursor lesion prostatic intraepithelial neoplasia cells, and knockdown of PRNCR1 decreased the viability of PC cells and the transactivation activity of androgen receptors. The authors suggest that PRNCR1 might play a role in PC growth through the androgen receptor-mediated pathway.