A prospective study of BK-virus-associated haemorrhagic cystitis in paediatric patients undergoing allogeneic haematopoietic stem cell transplantation

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MYC regulates a pan-cancer network of co-expressed oncogenic splicing factors.

MYC is dysregulated in \u3e50% of cancers, but direct targeting of MYC has been clinically unsuccessful. Targeting downstream MYC effector pathways represents an attractive alternative. MYC regulates alternative mRNA splicing, but the mechanistic links between MYC and the splicing machinery in cancer remain underexplored. Here, we identify a network of co-expressed splicing factors (SF-modules) in MYC-active breast tumors. Of these, one is a pan-cancer SF-module correlating with MYC activity across 33 tumor types. In mammary cell models, MYC activation leads to co-upregulation of pan-cancer module SFs and to changes in \u3e4,000 splicing events. In breast cancer organoids, co-overexpression of the pan-cancer SF-module induces MYC-regulated splicing events and increases organoid size and invasiveness, while knockdown decreases organoid size. Finally, we uncover a MYC-activity pan-cancer splicing signature correlating with survival across tumor types. Our findings provide insight into the mechanisms of MYC-regulated splicing and for the development of therapeutics for MYC-driven tumors

Differential Functions of Splicing Factors in Mammary Transformation and Breast Cancer Metastasis

Misregulation of alternative splicing is a hallmark of human tumors, yet to what extent and how it contributes to malignancy are only beginning to be unraveled. Here, we define which members of the splicing factor SR and SR-like families contribute to breast cancer and uncover differences and redundancies in their targets and biological functions. We identify splicing factors frequently altered in human breast tumors and assay their oncogenic functions using breast organoid models. We demonstrate that not all splicing factors affect mammary tumorigenesis in MCF-10A cells. Specifically, the upregulation of SRSF4, SRSF6, or TRA2beta disrupts acinar morphogenesis and promotes cell proliferation and invasion in MCF-10A cells. By characterizing the targets of these oncogenic splicing factors, we identify shared spliced isoforms associated with well-established cancer hallmarks. Finally, we demonstrate that TRA2beta is regulated by the MYC oncogene, plays a role in metastasis maintenance in vivo, and its levels correlate with breast cancer patient survival

Counting on co-transcriptional splicing

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An updated follow-up of chronic hepatitis C after three decades of observation in pediatric patients cured of malignancy

BACKGROUND: The aim of the study was to evaluate the clinical characteristics and the long-term outcome of chronic hepatitis C in a cohort of Caucasian children cured of pediatric malignancy. PROCEDURE: The study population included 83 consecutive patients, referred to our Center with a diagnosis of leukemia/lymphoma (50) or solid tumors (33) between 1977 and 1989 and infected with hepatitis C virus (HCV) during chemotherapy. RESULTS: At enrollment 77 subjects were HCV-RNA positive. After a median follow-up of 21 years (range 13-36), a sustained virological response (SVR) was obtained in 3 of 29 patients (10%) treated with interferon (IFN), in 1 of 3 patients (33%) treated with IFN and ribavirin, and in 5 of 11 patients (42%) treated with pegylated-IFN and ribavirin (P = 0.03). Forty-two patients remained untreated and only one (2.5%) cleared viremia. Four of 77 patients (5%) developed cirrhosis while other 4 patients died of causes not related to liver. At last follow-up, 72% of HCV-RNA positive patients had abnormal ALT. CONCLUSIONS: In patients cured of pediatric malignancy chronic hepatitis C tends to run an indolent course during childhood and adolescence but more than 70% of treated and more than 80% of untreated cases children maintained HCV viremia. Moreover, after 2-3 decades of observation, 60% of HCV-RNA positive patients had abnormal ALT and 5% had developed cirrhosis. Among treated patients, IFN or pegylated-IFN and ribavirin obtained the higher rate of HCV-RNA clearanc

Hyperbaric therapy (HT) in the treatment of hemorhragic cystitis (HC) after bone marrow transplantation

Retrospective results of hyperbaric therapy in a group of pediatric patients who underwent HSC