Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone marrow (BM) and peripheral blood (PB) involvement in 10 patients with mantle cell lymphoma (MCL) was analysed by a polymerase chain reaction (PCR)-mediated RNase protection assay. The complementarity determining regions (CDR)-III of all 10 MCLs examined was amplified efficiently with consensus V(H) and J(H) primers by PCR. and BM and/or PB involvement was evaluated by RNase protection assay in all 10 patients examined. Our assay showed BM and/or PB of the entire group to have neoplastic cells at presentation, despite the fact that eight patients were found to have BM and/or PB involvement on the basis of morphological examination and/or surface marker analysis. We also examined minimal residual disease (MRD) after conventional chemotherapy, and detected MRD in a patient in complete remission (CR). Although previous studies have shown that t(11;14) breakpoint amplification by PCR was only applicable to about 30-40% of cases, the present study indicates that CDR-III is a useful molecular marker and the PCR-mediated RNase protection assay is a good tool for the evaluation of MRD in MCL. It is suggested that BM and PB of MCL patients are quite frequently involved at presentation and even after conventional chemotherapy at the molecular level.
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PMID:Complementarity determining region-III is a useful molecular marker for the evaluation of minimal residual disease in mantle cell lymphoma. 926 40

Inositol-requiring enzyme 1 (IRE-1) is a kinase/RNase ER stress sensor that is activated in response to excessive accumulation of unfolded proteins, hypoxic conditions, calcium imbalance, and other stress stimuli. Activation of IRE-1 RNase function exerts a cytoprotective effect and has been implicated in the progression of cancer via increased expression of the transcription factor XBP-1s. Here, we describe the synthesis and biological evaluation of novel chromenone-based covalent inhibitors of IRE-1. Preparation of a family of 8-formyltetrahydrochromeno[3,4-c]pyridines was achieved via a Duff formylation that is attended by an unusual cyclization reaction. Biological evaluation in vitro and in whole cells led to the identification of 30 as a potent inhibitor of IRE-1 RNase activity and XBP-1s expression in wild type B cells and human mantle cell lymphoma cell lines.
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PMID:Synthesis of novel tricyclic chromenone-based inhibitors of IRE-1 RNase activity. 2474 61

The IRE-1 kinase/RNase splices the mRNA of the XBP-1 gene, resulting in the spliced XBP-1 (XBP-1s) mRNA that encodes the functional XBP-1s transcription factor that is critically important for the growth and survival of B-cell leukemia, lymphoma, and multiple myeloma (MM). Several inhibitors targeting the expression of XBP-1s have been reported; however, the cytotoxicity exerted by each inhibitor against cancer cells is highly variable. To design better therapeutic strategies for B-cell cancer, we systematically compared the ability of these compounds to inhibit the RNase activity of IRE-1 in vitro and to suppress the expression of XBP-1s in mouse and human MM cell lines. Tricyclic chromenone-based inhibitors B-I09 and D-F07, prodrugs harboring an aldehyde-masking group, emerged as the most reliable inhibitors for potent suppression of XBP-1s expression in MM cells. The cytotoxicity of B-I09 and D-F07 against MM as well as chronic lymphocytic leukemia and mantle cell lymphoma could be further enhanced by combination with inhibitors of the PI3K/AKT pathway. Because chemical modifications of the salicylaldehyde hydroxy group could be used to tune 1,3-dioxane prodrug stability, we installed reactive oxygen species-sensitive structural cage groups onto these inhibitors to achieve stimuli-responsive activities and improve tumor-targeting efficiency.
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PMID:Development of Tumor-Targeting IRE-1 Inhibitors for B-cell Cancer Therapy. 3305 62