PON2 blockade overcomes dexamethasone resistance in acute lymphoblastic leukemia
OBJECTIVES/UNASSIGNED:The high frequency of chemotherapy resistance is ultimately responsible for clinical relapse in acute lymphoblastic leukemia (ALL). Nevertheless, the molecular mechanism relevant to glucocorticoid (GC) resistance remains ambiguous. METHODS/UNASSIGNED:Quantitative real-time polymerase chain reaction and Western blot were performed to detect the expressions of paraoxonase 2 (PON2), Bcl-2 and Bax. shRNA was used to knockdown PON2 expression in SUP-B15 and REH cell. CCK-8 and flow cytometry assay were conducted to monitor the changes of proliferation and apoptosis in ALL cells. The growth of ALL REH cells in vivo was determined using transplanted tumor model. RESULTS/UNASSIGNED:This study was designed to identify GC resistance-associated genes by means of the transcriptome chip from the public Gene Expression Omnibus database, and preliminarily investigation of dexamethasone (DEX)-resistance mechanism in ALL. We disclosed that PON2 expression was elevated in ALL patients and especially higher in DEX-resistance ALL patients. Then, cell apoptosis assay suggested that silencing of PON2 dramatically promoted in DEX-resistant ALL cells apoptosis and the activity of Caspase 3 induced by DEX administration. In xenograft tumor model, PON2 knockdown significantly reduced DEX-resistant ALL cells growth in immunodeficient mice. CONCLUSIONS/UNASSIGNED:Collectively, inhibition of PON2 may represent a novel method to restore the sensitivity of treatment-resistant ALL to GC-induced cell death.
Duplication of the Extensor Pollicis Longus and Index Extensor Digitorum Communis: Report of a Novel Anomaly and Review of Literature
Distal Radius Fractures in the Elderly: Use of the Volar Bearing Plate
BACKGROUND:Distal radius fractures represent some of the most common injuries to the upper extremity, yet current evidence demonstrates great variability in the management of this injury. Elderly patients, in particular, stand to benefit from the early mobilization provided by operative fixation with a volar bearing plate. METHODS:We conducted a retrospective chart review on all patients 65 years or older who underwent unilateral open reduction internal fixation of distal radius fractures using a volar bearing plate at a single institution between January 2014 and January 2016. We excluded patients with bilateral injuries, multiple fractures, and major injuries to the same extremity. RESULTS:Fifty-five patients met criteria for this study. By AO classification, we repaired 17 type A, 24 type B, and 14 type C fractures. At final radiographic measurements, average radial height compared with ulna measured -0.31 mm, average radial inclination measured 20.45 degrees, and average volar tilt measured 7.11 degrees. On discharge, 36 patients had wrist range-of-motion data consistent with a functional wrist. Four patients had limitations in the flexion/extension plane, 8 with radial-ulnar deviation, and 7 had limitations in both planes. CONCLUSIONS:Distal radius fractures in the elderly may successfully be treated with a volar bearing plate. Useful strategies include supraperiosteal dissection of the radius from the pronator quadratus, use of a longer plate for stronger proximal fixation in osteoporotic bone, and regional block. This methodology allows for a safe procedure facilitating the early return of hand and wrist function.
An enigmatic brainstem posterior fossa ganglioglioma in an adult [Case Report]
Ganglioglioma is a rare central nervous system neoplasm representing 0.4% to 1.7% of all brain tumors and most frequently occurs in the pediatric population with an incidence of 7.6%. These tumors are usually slow-growing and well-circumscribed solid or cystic lesions. Gangliogliomatosis infrequently occurs in the frontal lobe, pineal gland, basal ganglia, hypothalamus, and optic chiasm, with very few reports of brainstem ganglioglioma. We report a case of a 35-year-old female who initially presented with headache, vertigo, ataxia, saccadic dysfunction, dysarthria, and dysmetria for several years due to an unknown etiology. Her brain imaging showed multiple lesions in the pons and the cerebellum with cystic changes and size reduction and enlargement over the next few years while her neurological symptoms continued to worsen. The patient received courses of steroid treatment that improved her neurological symptoms, suggesting an inflammatory component of her disease. Extensive workup for an inflammatory or infectious etiology was unfruitful and two brain biopsies were inconclusive. A third biopsy showed atypical glial nuclei, binucleated cells, and Rosenthal fibers and the presence of BRAF V600E mutation was detected. The diagnosis of gangliogliomatosis was consequently established. This case illustrates that gangliogliomatosis may present with the waxing-and-waning neurological signs and symptoms. It can masquerade inflammatory processes in the central nervous system on brain imaging and deserves careful consideration in the diagnosis of patients with an indolent course of neurological deterioration.