3 research outputs found

    Effect of Rat Strain Stereotactic Coordinates on Infarct Volume

    Get PDF
    Ischemic stroke makes up 87% of all hospital-admitted stroke cases annually; the primary treatment for these cases is intravenous administration of tPA within a 3.5 hour window from stroke onset. A long-term delayed ischemic stroke treatment proposed by this study was a combination of the pharmaceuticals Fluoxetine (SSRI), Simvastatin (statin), and ascorbic acid (Vitamin C). 51 adult rat subjects (10-12 months of age; 44 Sprague Dawley, 7 Long Evans) were given a combination of the drugs for 31 days. Drugs were given through voluntary oral administration via sugar cookie-dough balls to reduce inhibition of neurogenesis through stress-related glucocorticoid production. Drug combinations were as follows: FSA - 5 mg/kg fluoxetine, 0.5 mg/kg simvastatin and 20 mg/kg ascorbic acid; FS - 5 mg/kg fluoxetine, 0.5 mg/kg simvastatin; and the vehicle control. Endothelin-induced cortical stroke was administered using 2 different set of coordinates relative to bregma: Group 1 - (AP: 0.0 mm, ML: -2.5 mm) and (AP +1.5 mm; ML: -2.5 mm); Group 2 - (AP: 0.0 mm, ML: -2.5mm) and (AP +2.3; ML -2.5 mm). To analyze functional deficit, rats were subject to Montoya Staircase functional test once pre-stroke and twice post-stroke, and the Forelimb Asymmetry functional test once pre-stroke and thrice post-stroke. Results showed that Long Evans rats sustain a significantly larger infarct volume compared to Sprague Dawley rats using Group 2 coordinates; Group 1 cortical injection coordinates produced a larger infarct than Group 2 coordinates in FSA Sprague Dawley rats; drug treatment showed no effect on total infarct volume, however, this may be attributed to use of generic fluoxetine in Group 2 Sprague Dawley rats

    Comprehensive serial molecular profiling of an “N of 1” exceptional non-responder with metastatic prostate cancer progressing to small cell carcinoma on treatment

    Get PDF
    Abstract Importance Small cell carcinoma/neuroendocrine prostate cancer (NePC) is a lethal, poorly understood prostate cancer (PCa) subtype. Controversy exists about the origin of NePC in this setting. Objective To molecularly profile archived biopsy specimens from a case of early-onset PCa that rapidly progressed to NePC to identify drivers of the aggressive course and mechanisms of NePC origin and progression. Design, setting, and participants A 47-year-old patient presented with metastatic prostatic adenocarcinoma (Gleason score 9). After a 6-month response to androgen deprivation therapy, the patient developed jaundice and liver biopsy revealed exclusively NePC. Targeted next generation sequencing (NGS) from formalin-fixed paraffin-embedded (FFPE)-isolated DNA was performed from the diagnostic prostate biopsy and the liver biopsy at progression. Intervention Androgen deprivation therapy for adenocarcinoma followed by multiagent chemotherapy for NePC. Main outcomes and measures Identification of the mutational landscape in primary adenocarcinoma and NePC liver metastasis. Whether the NePC arose independently or was derived from the primary adenocarcinoma was considered based on mutational profiles. Results A deleterious somatic SMAD4 L535fs variant was present in both prostate and liver specimens; however, a TP53 R282W mutation was exclusively enriched in the liver specimen. Copy number analysis identified concordant, low-level alterations in both specimens, with focal MYCL amplification and homozygous PTEN, RB1, and MAP2K4 losses identified exclusively in the NePC specimen. Integration with published genomic profiles identified MYCL as a recurrently amplified in NePC. Conclusions and relevance NGS of routine biopsy samples from an exceptional non-responder identified SMAD4 as a driver of the aggressive course and supports derivation of NePC from primary adenocarcinoma (transdifferentiation).http://deepblue.lib.umich.edu/bitstream/2027.42/113670/1/13045_2015_Article_204.pd
    corecore