It would take years to accumulate significant
numbers of samples from IAR with histologically proven PanIN2/3 lesions, even in a multicenter study. Nevertheless, the detected significance is strong underscoring the strengths of the finding. Second, neither the murine nor the human samples originated from living beings with pure PanIN2 or PanIN3 lesions, so that we could not determine, whether or to which extent miR-196a and -196b were exclusively expressed by either PanIN2 or PanIN3 lesions. Third, meanwhile other promising miRNAs such as miR-221, miR-27a-3p, miR-10b, and Vorinostat RNU2-1f were reported [41], [42], [43], [44] and [45] that might also have potential value for the diagnosis of PC. However, there are no studies yet that analyzed their discriminatory potential between patients with different PanIN lesions and invasive cancer. In summary, the present study provides first evidence that miR-196a and -196b might be promising biomarkers for the detection of multifocal selleck inhibitor high-grade PanIN lesions and PC in IAR of FPC families. These results should be validated in larger controlled trials. If confirmed, these biomarkers could supplement imaging for an adequate timing of a curative pancreatic resection in IAR of FPC families. This work was supported by the Deutsche Krebshilfe (109126 to E.P.S., V.F., P.L., and
D.K.B.). There exists no financial or other relationship that might lead to a conflict of interest. We thank Helena Honig and Aninja Baier for their excellent technical assistance. We express our appreciation to all patients who participated in the Ceramide glucosyltransferase study. “
“Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide [1]. Transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres is one of the many treatment options available for patients with unresectable HCC. Because tumors in the liver derive most of their blood supply from the hepatic artery versus the portal vein [2], this therapy preferentially targets the tumor and spares uninvolved liver parenchyma. Prior reports have shown that TARE with 90Y
microspheres is associated with a 42% partial response rate [3] and [4] and longer progression-free survival than chemoembolization [5]. Concurrent chemoradiotherapy has proven to be more efficacious than radiation alone in the majority of gastrointestinal malignancies. A drug which preferentially sensitizes HCC to the cytotoxic effects of low dose rate radiation (LDR) produced by 90Y microspheres would potentially improve the efficacy of this therapy. Candidate drugs for radiosensitization include gemcitabine and 5-fluorouracil (5-FU) in addition to agents with known efficacy in HCC such as sorafenib. Gemcitabine and 5-FU are used routinely in combination with external beam radiation therapy for several intra-abdominal malignancies including pancreatic and gastric cancer [6], [7] and [8].