Highlights d Proteomic profiles of extracellular vesicles and particles (EVPs) from 426 human samples d Identification of pan-EVP markers d Characterization of tumor-derived EVP markers in human tissues and plasma d EVP proteins can be useful for cancer detection and determining cancer type

Decitabine (DAC) and 5-azacitidine have recently been approved for the treatment of myelodysplastic syndrome. The pharmacodynamic effects of DAC and 5-azacitidine outside their known activity as inhibitors of DNA methyltransferases (DNMTs) require further investigation. The purpose of this study was to investigate the effect of DAC on the expression of p21 WAF1/CIP1 , a gene with a putative CpG island surrounding its promoter region. Promoter methylation analysis of p21 WAF1/CIP1 in leukemia cells revealed the absence of CpG methylation. However, DAC upregulated p21 WAF1/CIP1 expression in a dosedependent manner (ED 50 ¼ 103.34 nM) and induced G2/M cell cycle arrest in leukemia cells. Sequential application of DAC followed by different histone deacetylase inhibitors induced expression of p21 WAF1/CIP1 synergistically. Upregulation of p21 WAF1/CIP1 paralleled DAC-induced apoptosis (ED 50 ¼ 153 nM). Low doses of DAC induced c-H2AX expression (ED 50 ¼ 16.5 nM) and upregulated p21 WAF1/CIP1 in congenic HCT 116 colon cancer cells in a DNMT-independent and p53-dependent fashion. Inhibition of p53 transactivation by pifithrin-a or the kinase activity of ATM by either the specific ATM inhibitor KU-5593 or caffeine abrogated p21 WAF1/CIP1 upregulation, indicating that DAC upregulation of p21 WAF1/CIP1 was p53-and ATM-dependent in leukemia cells. In conclusion, DAC upregulates p21 WAF1/CIP1 in DNMT-independent manner via the DNA damage/ATM/ p53 axis.

Background Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of adolescence and childhood. Although most patients with localized RMS are cured, outcome of those with metastatic disease remains unsatisfactory. RMS with bone marrow (BM) metastasis accounts for approximately 6% of all cases with RMS and has a 3‐year event‐free survival of 14%. Our study aims to describe our institution's experience of patients with metastatic RMS with BM involvement. Methods This was a single‐institution retrospective study from Memorial Sloan Kettering Kids, a tertiary pediatric oncology center. Patients with RMS who were diagnosed with BM metastasis between 1998 and 2018 were identified from pathology reports. Results For patients with RMS and BM positivity at diagnosis (N = 27), the median survival was 1.5 years. The 1‐, 2‐, and 3‐year overall survival (OS) were 81%, 32%, and 20%, respectively. There is one long‐term (defined as >4 year) survivor who is still alive 14.9 years after diagnosis despite two metastatic recurrences. An Oberlin status of 4 that included BM metastasis portended a 3‐year OS of 0%. Conclusions Although most patients will respond to initial therapy, BM metastasis at the time of diagnosis lends a near‐fatal diagnosis in pediatric patients with RMS. Novel therapies are desperately needed to consolidate their initial remission.

Purpose Desmoplastic small round cell tumor (DSRCT) is a rare cancer that predominantly affects males averaging 21 years of age at the time of diagnosis. We describe four cases from our institution and place them within the context of a comprehensive review of the literature. Patients and Methods Study population included any patient who received treatment at Children's Hospital at Montefiore (CHAM) with histologic diagnosis of DSRCT. A search of the electronic databases PubMed, Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE for the terms “desmoplastic” AND “small” AND “round” AND “cell” AND “tumor” was performed. Results One CHAM patient died of disease at 39 months, one patient has relapsed disease at 40 months, and two patients have no evidence of disease at 60 and 91 months. In the literature review, the 3-year OS was 36% and 5-year OS was 13%. There was a statistically significant difference in OS between no transplant and SCT in remission (p=0.004); however, there was no difference between no transplant and SCT not in remission (p=0.23). Conclusion Given the poor prognosis in DSRCT, this study supports further prospective research into the possible benefit of consolidation of autologous SCT in patients with DSRCT who are in remission, with the alternative inference that these patients in remission may fare well without SCT. Our retrospective review of the literature does not support SCT for patients who are not in remission.