Previous studies have shown that both long intergenic non-coding RNA 00963 (Linc00963) and tripartite motif containing 24 (TRIM24) are activators of the PI3K/AKT pathway, and both are involved in the carcinogenesis and progression of prostate cancer. However, the regulatory mechanisms between Linc00963 and TRIM24 are still unclear. In this study, we aimed to elucidate the underlying relationship between Linc00963 and TRIM24 in castration-resistant prostate cancer (CRPC). We found that TRIM24, an established oncogene in CRPC, was positively correlated with Linc00963 in prostate cancer tissues. In addition, TRIM24 was positively regulated by Lin00963 in CRPC cells. Mechanistically, TRIM24 was the direct target of microRNA-655 (miR-655) in CRPC cells, and Linc00963 could competitively bind miR-655 and upregulate TRIM24 expression. Using gain- and loss-of- function assays and rescue assays, we identified that miR-655 inhibits TRIM24 expression and cell proliferation and colony forming ability in CRPC, and that Linc00963 promotes TRIM24 expression, cell proliferation, and colony forming ability of CRPC cells by directly suppressing miR-655 expression. We further identified that Linc00963 could promote tumor growth of CRPC cells by inhibiting miR-655 and upregulating TRIM24 axis in vivo. Taken together, our study reveals a new mechanism for the Linc00963/miR-655/TRIM24 competing endogenous RNA (ceRNA) network in accelerating cell proliferation in CRPC in vitro and in vivo, and suggests that Linc00963 could be considered a novel therapeutic target for CRPC.We previously showed that inducible nitric oxide synthase (iNOS) protein expression in melanoma tumor cells is associated with poor patient prognosis.  https://www.selleckchem.com/products/Irinotecan-Hcl-Trihydrate-Campto.html  Here, we analyzed the association between iNOS and the oncogenic PI3K-AKT pathway. TCGA data show that iNOS and phospho-Akt Ser473 expression were associated significantly only in the subset of tumors with genetically intact PTEN. Employing a stage III melanoma TMA, we showed that iNOS protein presence is significantly associated with shorter survival only in tumors with PTEN protein expression. These findings led to our hypothesis that the iNOS product, nitric oxide (NO), suppresses the function of PTEN and stimulates PI3K-Akt activation. Melanoma cells in response to NO exposure in vitro exhibited enhanced AKT kinase activity and substrate phosphorylation, as well as attenuated PTEN phosphatase activity. Biochemical analysis showed that NO exposure resulted in a post-translationally modified S-Nitrosylation (SNO) PTEN, which was also found in cells expressing iNOS. Our findings provide evidence that NO-rich cancers may exhibit AKT activation due to post-translational inactivation of PTEN. This unique activation of oncogenic pathway under nitrosative stress may contribute to the pathogenesis of iNOS in melanoma. Significance Our study shows that iNOS expression is associated with increased PI3K-AKT signaling and worse clinical outcomes in melanoma patients with wt (intact) PTEN. Mutated PTEN is already inactivated. We also demonstrate that NO activates the PI3K-AKT pathway by suppressing PTEN suppressor function concurrent with the formation of PTEN-SNO. This discovery provides insight into the consequences of inflammatory NO produced in human melanoma and microenvironmental cells. It suggests that NO-driven modification provides a marker of PTEN inactivation, and represents a plausible mechanism of tumor suppressor inactivation in iNOS expressing subset of cancers.
  To compare survival between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) for the treatment of ovarian cancer patients per our selective protocol.
 
  Between Sep 1
  , 2015, and Aug 31
  , 2017, 161 patients were enrolled in our prospective cohort. All of the patients received preoperative clinic-radiological assessments, according to the Suidan criteria for R0 resection. Patients with a score of 0-2 received PDS. Patients with a score of ≥3 were counseled on the choices of PDS, NACT, or an optional staging laparoscopy, according to the Fagotti criteria. Clinic-pathological data were prospectively collected until May 1
  , 2020, and the impacts of different treatment strategies on progression-free survival (PFS) and overall survival (OS) were analyzed.
 
  110 patients underwent PDS, and 51 patients received NACT with consequent interval debulking surgery. The R0 resection rate was 57.8%. All but one of the patients received platinum-based chemotherapy, and 105 (65.2%) patients were platinum-sensitive. Based on the univariate analysis, the PDS group exhibited prolonged PFS compared with the NACT group (P=0.029). The subgroup analysis showed that patients receiving NACT with residual disease (RD) exhibited the worst PFS (P=0.001). Based on the multivariate analysis, NACT with RD was still an independent impaired factor for PFS (P=0.04). However, NACT did not affect OS in the univariate or multivariate analyses.
 
  In our prospective cohort, NACT ovarian patients exhibited inferior PFS and noninferior OS compared with PDS patients. Given our selective protocol, NACT cannot be arbitrarily denied while appropriate PDS is still a priority.
 In our prospective cohort, NACT ovarian patients exhibited inferior PFS and noninferior OS compared with PDS patients. Given our selective protocol, NACT cannot be arbitrarily denied while appropriate PDS is still a priority.As an important regulatory mechanism at the posttranscriptional level in metazoans, adenosine deaminase acting on RNA (ADAR)-induced A-to-I RNA editing modification of double-stranded RNA has been widely detected and reported. Editing may lead to non-synonymous amino acid mutations, RNA secondary structure alterations, pre-mRNA processing changes, and microRNA-mRNA redirection, thereby affecting multiple cellular processes and functions. In recent years, researchers have successfully developed several bioinformatics software tools and pipelines to identify RNA editing sites. However, there are still no widely accepted editing site standards due to the variety of parallel optimization and RNA high-seq protocols and programs. It is also challenging to identify RNA editing by normal protocols in tumor samples due to the high DNA mutation rate. Numerous RNA editing sites have been reported to be located in non-coding regions and can affect the biosynthesis of ncRNAs, including miRNAs and circular RNAs. Predicting the function of RNA editing sites located in non-coding regions and ncRNAs is significantly difficult.