Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on provisional clinical diagnosis, the choice of computed cranial tomography (CCT) or radionuclide brain scan (RBS) was retrospectively evaluated. In 1,333 selected cases, 551 had CCT only, 560 had RBS only, and 222 had both. CCT was the clinician's preference in cases of dementia, hydrocephalus, hemorrhage, aneurysm, arteriovenous malformation (AVM), primary tumor, visual abnormality, coma, and multiple sclerosis. RBS was preferred in headache, syncope, seizure, transient ischemic attack (TIA), metastatic disease, and encephalitis. Neither procedure appeared preferable in cases of psychosis, psychiatric disease, cerebral vascular accident (CVA), and abscess. Thirty-eight percent of CCTs yielded abnormal findings, not necessarily correlated with the provisional diagnosis. Thirty percent of RBS showed positive findings, mostly related to vascular abnormalities. On the basis of the provisional clinical diagnosis, CCT was more frequently requested for probable structural changes and RBS for probable perfusion abnormalities.
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PMID:Utility of the provisional clinical diagnosis as a basis for selection of computed tomographic or radionuclide brain scan. 727 14

Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a short median survival despite multimodal therapy. FTY720, an immunosuppressive drug approved for the treatment of multiple sclerosis, promotes MCL cell death concurrent with down-modulation of phospho-Akt and cyclin D1 and subsequent cell-cycle arrest. However, the mechanism of FTY720-mediated MCL cell death remains to be fully clarified. In the present study, we show features of autophagy blockage by FTY720 treatment, including accumulation of autolysosomes and increased LC3-II and p62 levels. We also show that FTY720-induced cell death is mediated by lysosomal membrane permeabilization with subsequent translocation of lysosomal hydrolases to the cytosol. FTY720-mediated disruption of the autophagic-lysosomal pathway led to increased levels of CD74, a potential therapeutic target in MCL that is degraded in the lysosomal compartment. This finding provided rationale for examining combination therapy with FTY720 and milatuzumab, an anti-CD74 mAb. Treatment of MCL cell lines and primary tumor cells with FTY720 and milatuzumab resulted in statistically significant enhanced cell death, which was synergistic in blastic variant MCL cell lines. Significant in vivo therapeutic activity of combination treatment was also demonstrated in a preclinical, in vivo model of MCL. These findings support clinical evaluation of this combination in patients with MCL.
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PMID:FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death. 2204 94