I n this issue of Pediatric Blood & Cancer, Orgel et al. [1] report the prevalence of early post-treatment cardiac dysfunction in a multi-center, retrospective cohort of childhood acute myeloid leukemia (AML) survivors. After a median follow-up of 13 months from the end of treatment, patients demonstrated an 8.7% decline in left ventricular shortening fraction (LVSF) from baseline to the most r...

The biosynthesis pathways of two anthracyclines, nogalamycin and aclacinomycin, were directed toward angucyclines by using an angucycline-specific cyclase, pgaF, isolated from a silent antibiotic biosynthesis gene cluster. Addition of pgaF to a gene cassette that harbored the early biosynthesis genes of nogalamycin resulted in the production of two known angucyclinone metabolites, rabelomycin a...

•Baseline PN was associated with longer on-study and a lower resolution rate in both study arms.•Prior platinum more grade 3-4 thrombocytopenia T-DM1, but not ?3 hemorrhage.•IDFS benefit T-DM1 versus trastuzumab similar irrespective of neoadjuvant therapy containing anthracyclines.•T-DM1 an increased overall risk CNS recurrence.•The IDFS maintained high-risk tumors defined by operable status, n...

Neoadjuvant chemotherapy (NC) is standard therapy for patients with locally advanced breast cancer and is increasingly used for early-stage operable disease. The aim of NC is a pathological complete response (pCR) in the breast and axillary lymph nodes, which is the best predictor of improved outcome and prolonged survival. The taxanes docetaxel and paclitaxel are potent agents in breast cancer...

PURPOSE DNA methyltransferase 3A (DNMT3A) is one of the commonly mutated genes in acute myelogenous leukemia (AML). Reports on the prognostic significance of DNMT3A mutations have been inconsistent, and most of the data are available only for patients 60 years of age or younger. We hypothesized that this inconsistency is due to an interaction between the dose of anthracycline used in induction ...

The second mitochondria‑derived activator of caspases (Smac), an antagonist of the inhibitor of apoptosis protein (IAP), increases chemosensitivity in vitro. Survivin, an IAP family member, mediates cancer cell survival and chemoresistance. The present study investigated the correlation between Smac and survivin expression in primary breast cancer, and the sensitivity to anthracycline during ne...

Inhibitors of the proteasome, a multicatalytic proteinase complex responsible for intracellular proteolysis, activate programmed cell death in part through the c-Jun-N-terminal kinase (JNK). Proteasome inhibitors also induce mitogen-activated protein kinase phosphatase-1 (MKP-1), however, which can inactivate JNK, and we therefore considered the hypothesis that MKP-1 induction may be antiapopto...

Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignancy of putative NK-cell origin, with a minority deriving from the T-cell lineage. Pathologically, the malignancy occurs in two forms, extranodal NK/T-cell lymphoma, nasal type; and aggressive NK-cell leukaemia. Lymphoma occur most commonly (80%) in the nose and upper aerodigestive tract, less commonly (20%) in non-nasal area...

Previous fluorescence microscopic studies have shown daunorubicin (DNR) and Adriamycin (ADR) are localized in cell nuclei, whereas trifluoroacetyladriamycin-14-valerate is local ized in the cytoplasm. Using cultured cells, we correlated structural characteristics of a series of anthracycline antibiotics with cellular disposition and metabolic response. When ob served under fluorescence microsco...