1c:I[776865,["/_next/static/chunks/bb923814e1f4d2e9.js","/_next/static/chunks/dd3ee9f5b7716ca6.js","/_next/static/chunks/4204a0ae82542ca8.js","/_next/static/chunks/30036bedc5269936.js","/_next/static/chunks/6e1aa89a642f40be.js","/_next/static/chunks/cd5e572bc3e4eb92.js","/_next/static/chunks/8ffd0b71567920d8.js","/_next/static/chunks/67ea6dfd21f16c5f.js","/_next/static/chunks/24eb4379f68013fd.js","/_next/static/chunks/b8cd775ffdf935bd.js","/_next/static/chunks/983103cd9eb7b428.js","/_next/static/chunks/d4ac9dcf27f6ff52.js","/_next/static/chunks/294b9525248c8e5f.js"],"Grid"] 1d:I[617291,["/_next/static/chunks/bb923814e1f4d2e9.js","/_next/static/chunks/dd3ee9f5b7716ca6.js","/_next/static/chunks/4204a0ae82542ca8.js","/_next/static/chunks/30036bedc5269936.js","/_next/static/chunks/6e1aa89a642f40be.js","/_next/static/chunks/cd5e572bc3e4eb92.js","/_next/static/chunks/8ffd0b71567920d8.js","/_next/static/chunks/67ea6dfd21f16c5f.js","/_next/static/chunks/24eb4379f68013fd.js","/_next/static/chunks/b8cd775ffdf935bd.js","/_next/static/chunks/983103cd9eb7b428.js","/_next/static/chunks/d4ac9dcf27f6ff52.js","/_next/static/chunks/294b9525248c8e5f.js"],"GridCol"] 1e:I[419806,["/_next/static/chunks/bb923814e1f4d2e9.js","/_next/static/chunks/dd3ee9f5b7716ca6.js","/_next/static/chunks/4204a0ae82542ca8.js","/_next/static/chunks/30036bedc5269936.js","/_next/static/chunks/6e1aa89a642f40be.js","/_next/static/chunks/cd5e572bc3e4eb92.js","/_next/static/chunks/8ffd0b71567920d8.js","/_next/static/chunks/67ea6dfd21f16c5f.js","/_next/static/chunks/24eb4379f68013fd.js","/_next/static/chunks/b8cd775ffdf935bd.js","/_next/static/chunks/983103cd9eb7b428.js","/_next/static/chunks/d4ac9dcf27f6ff52.js","/_next/static/chunks/294b9525248c8e5f.js"],"default"] 1f:T404,Mebendazole was given to four patients with hepatic hydatid disease. In three patients hydatidosis had remained after surgery, and in the fourth it could not be treated surgically. Mebendazole was given orally in maximum doses of 400-600 mg three times a day during courses lasting 21 to 30 days. Ultrasonic echotomography showed a complete regression of the intrahepatic cysts after four to 13 months in all four cases. In three patients the course of treatment had to be repeated. Mebendazole also induced clinical improvement and a progressive lowering of the concentration of specific IgE of Echinococcus granulosus. During treatment circulating blood levels of specific immune complexes of antigen 5 were increased. These observations indicate that mebendazole has a lethal effect on E granulosus cysts in primary hydatid disease in man and that the efficacy of chemotherapy can be assessed with ultrasonography and by measuring changes in the concentration of specific IgE of E granulosus and circulating immune complexes.20:T51f,

ABSTRACT

Despite advancement in treatment, prostate cancer (PCa) remains the second leading cause of death among men. Neuroendocrine prostate cancer (NEPC) represents one of the most lethal forms of PCa and lacks life-prolonging treatment. Here we identified histone lysine demethylase KDM4A as a drive in NEPC progression and an effective therapeutic target. We found that KDM4A mRNA and protein are overexpressed in human and mouse NEPC compared to adenocarcinoma. Also, we showed that knockdown or knockout of KDM4A in NEPC cell lines suppressed cancer cell growth in vitro and in vivo. Importantly, inactivation of Kdm4a in a genetically engineered mouse model of prostate cancer led to reduced tumor burden, reduced incidence of NEPC, and prolonged overall survival. Mechanistically, we found that KDM4A KD led to suppression of MYC signaling through direct transcriptional regulation of MYC. Importantly, MYC signaling is hyper-activated in human and mouse NEPC. Furthermore, a potent pan-KDM4 inhibitor QC6352 significantly reduced NEPC cell growth in vitro and in vivo. Taken together, we demonstrated that KDM4A drives NEPC progression through regulation of MYC and targeting KDM4A can potentially be an effective therapeutic strategy f

	Year	Citations

Abstract

References