Glucocorticoids (GCs) induce apoptosis in lymphoid lineage cells and are therefore used in the therapy of acute lymphoblastic leukemia (ALL) and related malignancies. MicroRNAs (miRNAs) and the related mirtrons are B22 nucleotide RNAs derived from polymerase-II transcripts and implicated in the control of essential biological functions, including apoptosis. Whether GCs regulate miRNA-encoding transcription units is unknown. We investigated miRNA/mirtron expression and GC regulation in 8 leukemia/lymphoma in vitro models and 13 ALL children undergoing systemic GC monotherapy using a combination of expression profiling techniques, real time reverse transcription (RT)-PCR and northern blotting to detect mature miRNAs and/or their precursors. We found that mature miRNA regulations can be inferred from expression data of their host genes. Although a simple miRNA-initiated canonical pathway to GC-induced apoptosis or cell cycle arrest did not emerge, we identified several miRNAs/mirtrons that were regulated by GC in patients and cell lines, including the myeloid-specific miR-223 and the apoptosis and cell cycle arrest-inducing miR15B16 clusters. In an in vitro model, overexpression of miR15bB16 mimics increased and silencing by miR15bB16 inhibitors decreased GC sensitivity. Thus, the observed complex changes in miRNA/mirtron expression during GC treatment might contribute to the anti-leukemic GC effects in a cell context-dependent manner.

Glucocorticoids (GCs) cause cell cycle arrest and apoptosis in lymphoid cells which is exploited to treat lymphoid malignancies. The mechanisms of these anti-leukemic GC effects are, however, poorly understood. We previously defined a list of GC-regulated genes by expression profiling in children with acute lymphoblastic leukemia (ALL) during systemic GC monotherapy and in experimental systems of GC-induced apoptosis. PLZF/ZBTB16, a transcriptional repressor, was one of the most promising candidates derived from this screen. To investigate its role in the anti-leukemic GC effects, we performed overexpression and knock-down experiments in CCRF-CEM childhood ALL cells. Transgenic PLZF/ZBTB16 alone had no detectable effect on cell proliferation or survival, but reduced sensitivity to GC-induced apoptosis but not apoptosis induced by antibodies against Fas/CD95 or 3 different chemotherapeutics. Knock-down of ZBTB16 entailed a small, but significant, increase in cell death induction by GC. Affymetrix Exon array-based whole genome expression profiling revealed that PLZF/ZBTB16 induction did not significantly alter the expression profile, however, it interfered with the regulation of numerous GC response genes, including BCL2L11/Bim, which has previously been shown to be responsible for cell death induction in CCRF-CEM cells. Thus, the protective effect of PLZF/ZBTB16 can be attributed to interference with transcriptional regulation by GC.

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DC-LC is safe and feasible in non-acute patients with symptomatic cholelithiasis. Over-55y age group had a higher chance of admission, mainly due to caution.

Hidradenocarcinoma is a rare and locally aggressive tumor rendering a poor prognosis. Furthermore, very few cases present with nodal metastasis. Diagnosing such an entity, and then differentiating it from a benign counterpart, poses a great challenge to the clinicians. There are no established treatment guidelines for the management of this disease, particularly in patients with nodal involvement.We present a case of a young male who was diagnosed with hidradenocarcinoma of the scalp, along with a neck swelling. A thorough diagnostic evaluation was done with endoscopy, pathological, and radiological investigations. He was successfully treated with resection of the scalp lesion and right-sided neck dissection followed by adjuvant concurrent chemoradiation. He remains free of any local and distant disease after five years of regular follow-up.

Apoptosis is a morphologically defined form of cell death that plays a major role in cell physiology, pathology and cancer therapy. The Bcl-2 family of pro- and anti-apoptotic molecules is a key regulator of this phenomenon, with the sub-family of BH3-only molecules serving as activators and/or facilitators. Apoptosis induced by glucocorticoids (GC) is a central component in the therapy of acute lymphoblastic leukemia (ALL), and defining its molecular basis and that of GC resistance is crucial for therapeutic improvements. We recently identified a novel transcript from the BCL2L11/Bim locus, termed "Bam", by affymetrix based whole genome expression profiling performed on 27 children (13 were already published) with ALL and many additional biological systems. Most children that induced Bam also induced Bim as well, in some cases Bam induction was more pronounced than that of Bim and in one patient only the Bam, but not Bim was induced. In C7H2, PreB697, Jurkat-GR(wt) and GC-sensitive (S-lines), this transcript was induced by GC in a translation-independent manner, suggesting that direct transcriptional induction of this BH3-only molecule by GC might cause apoptosis in at least ALL children and other biological systems.

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PURPOSE To evaluate and report the frequency of changes in radiation therapy treatment plans after peer review in a simulation review meeting once a week. MATERIALS AND METHODS Between July 1 and August 31, 2016, the radiation plans of 116 patients were discussed in departmental simulation review meetings. All plans were finalized by the primary radiation oncologist before presenting them in the meeting. A team of radiation oncologists reviewed each plan, and their suggestions were documented as no change, major change, minor change, or missing contour. Changes were further classified as changes in clinical target volume, treatment field, or dose. All recommendations were stratified on the basis of treatment intent, site, and technique. Data were analyzed by Statistical Package for the Social Sciences and are presented descriptively. RESULTS Out of 116 plans, 26 (22.4%) were recommended for changes. Minor changes were suggested in 15 treatment plans (12.9%) and a major change in 10 (8.6%), and only one plan was suggested for missing contour. The frequency of change recommendations was greater in radical radiation plans than in palliative plans (92.3% v 7.7%). The head and neck was the most common treatment site recommended for any changes (42.3%). Most of the changes were recommended in the technique planned with three-dimensional conformal radiation therapy (50%). Clinical target volume (73.1%) was identified as the most frequent parameter suggested for any change, followed by treatment field (19.2%) and dose (0.08%). CONCLUSION Peer review is an important tool that can be used to overcome deficiencies in radiation treatment plans, with a goal of improved and individualized patient care. Our study reports changes in up to a quarter of radiotherapy plans.