Small, noncoding RNAs are short untranslated RNA molecules, some of which have been associated with cancer development. Recently we showed that a class of small RNAs generated during the maturation process of tRNAs (tRNA-derived small RNAs, hereafter "tsRNAs") is dysregulated in cancer. Specifically, we uncovered tsRNA signatures in chronic lymphocytic leukemia and lung cancer and demonstrated that the ts-4521/3676 cluster (now called "ts-101" and "ts-53," respectively), ts-46, and ts-47 are down-regulated in these malignancies. Furthermore, we showed that tsRNAs are similar to Piwi-interacting RNAs (piRNAs) and demonstrated that ts-101 and ts-53 can associate with PiwiL2, a protein involved in the silencing of transposons. In this study, we extended our investigation on tsRNA signatures to samples collected from patients with colon, breast, or ovarian cancer and cell lines harboring specific oncogenic mutations and representing different stages of cancer progression. We detected tsRNA signatures in all patient samples and determined that tsRNA expression is altered upon oncogene activation and during cancer staging. In addition, we generated a knockedout cell model for ts-101 and ts-46 in HEK-293 cells and found significant differences in gene-expression patterns, with activation of genes involved in cell survival and down-regulation of genes involved in apoptosis and chromatin structure. Finally, we overexpressed ts-46 and ts-47 in two lung cancer cell lines and performed a clonogenic assay to examine their role in cell proliferation. We observed a strong inhibition of colony formation in cells overexpressing these tsRNAs compared with untreated cells, confirming that tsRNAs affect cell growth and survival.tsRNA | tRF | tDR | ncRNA | tRNA fragments

BACKGROUND. Because of scarce data from larger series and nonhomogeneous selection criteria, further information is needed on peritonectomy with hyperthermic intraperitoneal chemotherapy (HIPEC) in managing patients with ovarian peritoneal carcinomatosis. METHODS. In an open, prospective, single‐center nonrandomized phase 2 study conducted from November 2000 to April 2007, 47 patients with primary advanced or recurrent ovarian cancer and diffuse peritoneal carcinomatosis were enrolled; 22 underwent primary and 25 secondary cytoreduction plus immediate HIPEC followed by systemic chemotherapy. RESULTS. The overall mean Sugarbaker peritoneal cancer index was 14.9 (range, 6–28). A mean of 6 surgical procedures were required per patient (range, 4–10). In 87.3% of the patients debulking achieved optimal cytoreduction (Sugarbaker completeness of cytoreduction [CC] score 0–1), whereas in 12.7% it left macroscopic residual disease (CC‐2 or CC‐3). Major complications developed in 21.3% of the patients and the in‐hospital mortality rate was 4.2%. The mean overall survival was 30.4 months, median survival was 24 months, and mean disease‐free survival was 27.4 months. Five‐year survival was 16.7%. Univariate (log‐rank test and analysis of variance) and multivariate analyses (Cox proportional‐hazard model) identified the CC score as the main factor capable of independently influencing survival. CONCLUSIONS. Peritonectomy procedures combined with HIPEC offer promising long‐term survival in patients with diffuse peritoneal ovarian carcinomatosis. They achieve high adequate primary and secondary surgical cytoreduction rates with acceptable morbidity and mortality. Cancer 2008. © 2008 American Cancer Society.

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In comparison with CrD-SBC, CD-SBC patients harbour MSI and high TILs more frequently and show better outcome. This seems mainly due to their higher TIL density, which at multivariable analysis showed an independent prognostic value. MSI/TIL status, KRAS mutations and HER2 amplification might help in stratifying patients for targeted anti-cancer therapy.

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