Shortening of 3′UTRs Correlates with Poor Prognosis in Breast and Lung Cancer

A major part of the post-transcriptional regulation of gene expression is affected by trans-acting elements, such as microRNAs, binding the 3′ untraslated region (UTR) of their target mRNAs. Proliferating cells partly escape this type of negative regulation by expressing shorter 3′ UTRs, depleted of microRNA binding sites, compared to non-proliferating cells. Using large-scale gene expression datasets, we show that a similar phenomenon takes place in breast and lung cancer: tumors expressing shorter 3′ UTRs tend to be more aggressive and to result in shorter patient survival. Moreover, we show that a gene expression signature based only on the expression ratio of alternative 3′ UTRs is a strong predictor of survival in both tumors. Genes undergoing 3′UTR shortening in aggressive tumors of the two tissues significantly overlap, and several of them are known to be involved in tumor progression. However the pattern of 3′ UTR shortening in aggressive tumors in vivo is clearly distinct from analogous patterns involved in proliferation and transformation

Pressurized Intra Peritoneal Aerosol Chemotherapy in patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma

Patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma were treated with Pressurized Intra Peritoneal Aerosol Chemotherapy (PIPAC), initial clinical findings are presented.Single institution, tertiary referral center certified for therapy of peritoneal disease. Prospective data collection of PIPAC therapy with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2 of body surface delivered at intervals of six weeks. The outcome criteria were microscopic pathological response, survival and adverse events (v4.0 CTCAE).A total of 20 patients (m/f = 3:1) with a mean age of 64.9 (range: 45.0 to 87.0) years underwent 41 PIPAC procedures without intraoperative complications. The mean number of PIPAC cycles was 2.1 (range: one to four). Ten patients with ≥ 2 PIPAC applications were eligible for histological analysis to assess carcinoma regression. Complete or high grade tumor regression was found in two (10%) and five (25%) patients, respectively. An overall median survival of 36.6 weeks after the first PIPAC application was observed. One patient died postoperatively due to small bowel obstruction. No CTCAE level 3 and 4 complications occurred.In about one third of patients, repeated PIPAC therapy did induce histological regression of systemic chemo-resistant PC of pancreatic adenocarcinoma. Prospective randomized trials are needed to further clarify any clinical impact of such observations