MicroRNA and transcriptome analysis in periocular Sebaceous Gland Carcinoma

Sebaceous gland carcinoma (SGC) is a rare, but life-threatening condition with a predilection for the periocular region. Eyelid SGC can be broadly categorised into two subtypes, namely either nodular or pagetoid with the latter being more aggressive and requiring radical excision to save life. We have identified key altered microRNAs (miRNA) involved in SGC shared by both subtypes, hsa-miR-34a-5p and hsa-miR-16-5p. However, their gene targets BCL2 and MYC were differentially expressed with both overexpressed in pagetoid but unchanged in nodular suggesting different modes of action of these two miRNAs on BCL/MYC expression. Hsa-miR-150p is nodular-specifically overexpressed, and its target ZEB1 was significantly downregulated in nodular SGC suggesting a tumour suppressor role. Invasive pagetoid subtype demonstrated specific overexpression of hsa-miR-205 and downregulation of hsa-miR-199a. Correspondingly, miRNA gene targets, EZH2 (by hsa-miR-205) and CD44 (by hsa-miR-199a), were both overexpressed in pagetoid SGC. CD44 has been identified as a potential cancer stem cell marker in head and neck squamous cell carcinoma and its overexpression in pagetoid cells represents a novel treatment target. Aberrant miRNAs and their gene targets have been identified in both SGC subtypes, paving the way for better molecular understanding of these tumours and identifying new treatment targets

MicroRNA and transcriptome analysis in periocular Sebaceous Gland Carcinoma

Fight For Sight Fellowship, UK; National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHSFoundation Trust and UCL Institute of Ophthalmology. J.W. and C.C. acknowledge support from Cancer Research UK Centre of Excellence Award to Barts Cancer Centre [C16420/A18066

ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair

The DNA damage-induced ATM kinase is linked to the metabolic pentose phosphate pathway, thus boosting biosynthesis of nucleotide precursors required for DNA repair and stimulating generation of the anti-oxidant NADPH, which may explain neurological defects of ataxia telangiectasia patients lacking ATM function

Developmental patterns of glycolytic enzymes in regenerating skeletal muscle after autogenous free grafting

Extensor digitorum longus muscles of rats were removed and injected with a solution of Marcaine plus hyaluronidase. After incubation in Marcaine solution for 10 min, the muscles were grafted into their original beds. The grafts and the contralateral control muscles were removed from the rats at 0, 1-5, 7, 11, 36, and 69 days postoperatively. The muscles were then frozen in dry ice and isopentane and subsequently homogenized and centrifuged. The supernatant was analyzed for a number of enzymes, the regenerative patterns of which can be classified into 3 groups: (1) early increase in activity: hexokinase, glucose-6-phosphate dehydrogenase; (2) early decrease in activity with failure to recover to control levels: phosphorylase, phosphofructokinase, [alpha]-glycerophosphate dehydrogenase; and (3) early decrease followed by return to control levels: lactate dehydrogenase, pyruvate kinase, creatine phosphokinase, adenylate kinase. These patterns are not identical to those reported for embryogenesis of muscle. The data are discussed with regard to correlative histological studies of muscle regeneration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22796/1/0000352.pd

Dose management in CT facility

Computed Tomography (CT) examinations have rapidly increased in number over the last few years due to recent advances such as the spiral, multidetector-row, CT fluoroscopy and Positron Emission Tomography (PET)-CT technology. This has resulted in a large increase in collective radiation dose as reported by many international organisations. It is also stated that frequently, image quality in CT exceeds the level required for confident diagnosis. This inevitably results in patient radiation doses that are higher than actually required, as also stressed by the US Food and Drug Administration (FDA) regarding the CT exposure of paediatric and small adult patients. However, the wide range in exposure parameters reported, as well as the different CT applications reveal the difficulty in standardising CT procedures. The purpose of this paper is to review the basic CT principles, outline the recent technological advances and their impact in patient radiation dose and finally suggest methods of radiation dose optimisation

Analysis of hedgehog signaling in periocular sebaceous carcinoma

PURPOSE: Sebaceous carcinoma (SC) is a clinical masquerader of benign conditions resulting in significant eye morbidity, sometimes leading to extensive surgical treatment including exenteration, and even mortality. Little is known about the genetic or molecular basis of SC. This study identifies the involvement of Hedgehog (Hh) signaling in periocular SC. METHODS: Fifteen patients with periocular SC patients were compared to 15 patients with eyelid nodular basal cell carcinoma (nBCC; a known Hh tumor), alongside four normal individuals as a control for physiological Hh expression. Expression of Patched 1 (PTCH1), Smoothened (SMO), and glioma-associated zinc transcription factors (Gli1 and Gli2) were assessed in histological sections using immunohistochemistry and immunofluorescence (IF) techniques. Antibody specificity was verified using Western-blot analysis of a Gli1 over-expressed cancer cell line, LNCaP-Gli1. Semi-quantification compared tumors and control tissue using IF analysis by ImageJ software. RESULTS: Expression of the Hh pathway was observed in SC for all four major components of the pathway. PTCH1, SMO, and Gli2 were more significantly upregulated in SC (P < 0.01) compared to nBCC. Stromal expression of PTCH1 and Gli2 was observed in SC (P < 0.01). In contrast, stromal expression of these proteins in nBCC was similar or down-regulated compared to physiological Hh controls. CONCLUSIONS: The Hh signaling pathway is significantly more upregulated in periocular SC compared to nBCC, a known aberrant Hh pathway tumor. Furthermore, the stroma of the SC demonstrated Hh upregulation, in particular Gli2, compared to nBCC. Targeting of this pathway may be a potential treatment strategy for SC

Circulation in denervated limbs

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