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3.
Neurohospitalist ; 3(1): 15-9, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23983883

ABSTRACT

Neurologists should be familiar with the spectrum of central nervous system (CNS) pathology that renal transplants patients are prone to. We are presenting a case of posttransplant lymphoproliferative disorder of the CNS to highlight less commonly described imaging findings and review this disease entity.

4.
Oncol Lett ; 2(6): 1309-1312, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22848307

ABSTRACT

Exons 3 to 6 in the caspase 9 gene undergo alternative splicing in which the larger caspase 9 splice variant promotes apoptosis, in contrast to the dominant negative anti-apoptotic splice variant, the smaller caspase 9b. In this study, the regulation of the alternative splicing of caspase 9 pre-mRNA was examined in response to Emetine. Treatment of C33A cells, breast cancer MCF-7 cells and MCF-7/Adr cells with Emetine dihydrochloride upregulated the level of smaller caspase 9b mRNA and concomitantly decreased the mRNA level of larger caspase 9 in a dose- and time-dependent manner, indicating that Emetine desensitizes C33A, MCF-7 and MCF-7/Adr to cell death. In contrast, treatment of PC3 cells, a prostate cancer cell line, manifested an opposite effect: a greater production of the larger caspase 9 mRNA with a concomitant decrease of caspase 9b mRNA. Pretreatment with calyculin A, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) blocked Emetine-induced alternative splicing in cells, in contrast to okadaic acid, a specific inhibitor of PP2A, demonstrating a PP1-mediated mechanism. These results suggest that the various splicing patterns of the caspase 9 gene that are regulated by chemotherapy reagents may contribute to the resistance or sensitization of the tumors to other cell death inducers.

5.
Chem Biol ; 14(12): 1386-92, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18096507

ABSTRACT

Exon 2 of the Bcl-x gene undergoes alternative splicing in which the Bcl-xS splice variant promotes apoptosis in contrast to the anti-apoptotic splice variant Bcl-xL. In this study, the regulation of the alternative splicing of pre-mRNA of Bcl-x was examined in response to emetine. Treatment of different types of cancer cells with emetine dihydrochloride downregulated the level of Bcl-xL mRNA with a concomitant increase in the mRNA level of Bcl-xS in a dose- and time-dependent manner. Pretreatment with calyculin A, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), blocked emetine-induced alternative splicing in contrast to okadaic acid, a specific inhibitor of PP2A in cells, demonstrating a PP1-mediated mechanism. Our finding on the regulation of RNA splicing of members of the Bcl-2 family in response to emetine presents a potential target for cancer treatment.


Subject(s)
Alternative Splicing/drug effects , Emetine/pharmacology , Protein Phosphatase 1/metabolism , bcl-X Protein/genetics , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Cycloheximide/pharmacology , Down-Regulation/drug effects , Down-Regulation/genetics , Enzyme Inhibitors/pharmacology , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Marine Toxins , Okadaic Acid/pharmacology , Oxazoles/pharmacology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Protein Phosphatase 1/antagonists & inhibitors , Protein Phosphatase 2/antagonists & inhibitors , Protein Phosphatase 2/metabolism , Up-Regulation/drug effects , Up-Regulation/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology
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