Significance: Because of its selective expression on the surface of a variety of different cancer cells, but not on their normal counterparts, nucleolin (NCL) represents an attractive target for antineoplastic treatments. However, previously described NCL-targeting molecules, although promising, still suffer from intrinsic limitations. Here, we describe the identification of the first fully human anti-NCL immune-based agent displaying antineoplastic activity against solid tumors, both in vitro and in vivo. This molecule could represent the prototype of a novel class of NCL-targeting drugs with enormous clinical potential as tools for the diagnosis and therapy of a wide range of human cancers.

Quaking and miR-155 interactions in inflammation and leukemogenesis

Ran Binding Protein 9 (RanBP9) is a novel mediator of cellular DNA damage response in lung cancer cells

Purpose of reviewAs the population ages, urologic oncologists are caring for older and more vulnerable patients that must withstand complex surgical treatments. Our healthcare environment emphasizes surgical quality, reductions in length of hospital stay, reduced readmission rates, and high patient satisfaction. So those who manage urologic malignancies must be able to optimize their patients. Understanding the concept of frailty, how to diagnose it in a timely and reliable manner, appreciate its perioperative impact, and consider interventions to reduce its effects may improve surgical outcomes.Recent findingsThere has been a recent swell of early research regarding frailty in urologic oncology and its related perioperative effects. Increasing degrees of frailty are associated with greater morbidity and mortality, and more adverse discharge disposition after surgical procedures. Clinicians are, thus, recognizing the value of geriatric assessment in their practice and exploring ways to integrate it using a team-based approach. Universal geriatric recommendations are now available in specific urologic populations to guide these efforts. Importantly, formal geriatric assessment outperforms physician discretion or the eyeball' test.SummaryThe current review offers a comprehensive study of the impact of frailty in urologic oncology, methods for its assessment, and active interventions to reduce it.

IWS1 is an RNA-polymerase II (RNAPII)-associated transcription elongation factor whose biological functions are poorly characterized. To shed some light on the function of this protein at the organismal level, we performed a systematic tissue analysis of its expression and generated Iws1-deficient mice. A thorough immunohistochemical characterization shows that IWS1 protein is present in the nucleus of all cells in most of the examined tissues, with few notable exceptions. We also report that ablation of Iws1 consistently causes lethality at the pre-implantation stage with high expression of the gene in fertilized oocytes. In summary, we are providing evidence that Iws1 is expressed in all adult organs and it is an essential gene for mouse embryonic development.

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and second most common cause of cancer-related deaths in the United States. Androgen deprivation therapy (ADT) is only temporarily effective for advanced-stage PCa, as the disease inevitably progresses to castration-resistant prostate cancer (CRPC). The protein nucleolin (NCL) is overexpressed in several types of human tumors where it is also mislocalized to the cell surface. We previously reported the identification of a single-chain fragment variable (scFv) immuno-agent that is able to bind NCL on the surface of breast cancer cells and inhibit proliferation both in vitro and in vivo. In the present study, we evaluated whether NCL could be a valid therapeutic target for PCa, utilizing DU145, PC3 (CRPC), and LNCaP (androgen-sensitive) cell lines. First, we interrogated the publicly available databases and noted that higher NCL mRNA levels are associated with higher Gleason Scores as well as with recurrent and metastatic tumors. Then, using our anti-NCL scFv, we demonstrated that NCL is expressed on the surface of all three tested cell lines and that NCL inhibition results in reduced proliferation and migration. We also measured the inhibitory effect of NCL targeting on the biogenesis of oncogenic microRNAs such as miR-21, -221 and -222, which was cell context dependent. Taken together, our data provide evidence that NCL targeting inhibits the key hallmarks of malignancy in PCa cells and may provide a novel therapeutic option for patients with advanced-stage PCa.