ELIZA

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324223 occurrences (No.64 in the rank) during 5 years in the PubMed. [no cache] 500 found

249) Our study, for the first time, validated that the modest activation of the UPR pathway enables myeloma cells to further differentiate, and identified that XBP-1 plays an indispensable role in UPR-mediated myeloma cell differentiation and maturation.

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PMID:24356728 DOI:10.1007/s10238-013-0269-y

2015 Clinical and experimental medicine

* Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma cell differentiation mediated by XBP-1.

- The unfolded protein response (UPR) is an essential pathway for both normal and malignant plasma cells to maintain endoplasmic reticulum (ER) homeostasis in response to the large amount of immunoglobulin (Ig) output. The inositol-requiring enzyme 1-X-box binding protein-1 (IRE1-XBP-1) arm of the UPR pathway has been shown to play crucial roles not only in relieving the ER stress by up-regulating a series of genes favoring ER-associated protein degradation and protein folding, but in mediating terminal plasmacytic differentiation and maturation. Myeloma cells comprise various subsets arrested in diverse differentiated phases, and the immaturity of myeloma cells has been taken as a marker for poor prognosis, suggesting that differentiation induction would be a promising therapeutic strategy for myeloma. Herein, we used low-dose pharmacological UPR inducers such as tunicamycin (TM) and dithiothreitol (DTT) to efficiently activate the IRE1-XBP-1 pathway in myeloma cells characterized by transcriptional expression increase in spliced XBP-1 and molecular chaperons, accompanied by significant differentiation and maturation of these myeloma cells, without concomitant cytotoxicity. These differentiated myeloma cells exhibited a more mature appearance with well-developed cytoplasm and a reduced nucleocytoplasmic ratio, and a further differentiated phenotype with markedly increased expression of CD49e together with significantly elevated cellular secretion of Ig light chain as shown by flow cytometry and ELISA, in contrast to the control myeloma cells without exposed to TM or DTT. Moreover, siRNA knockdown of XBP-1 disrupted TM- or DTT-induced myeloma cell differentiation and maturation. Our study, for the first time, validated that the modest activation of the UPR pathway enables myeloma cells to further differentiate, and identified that XBP-1 plays an indispensable role in UPR-mediated myeloma cell differentiation and maturation. Thus, we provided the rationale and feasibility for the exploration of the novel therapeutic strategy of differentiation induction for plasmacytic malignancies.

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--- WordNet output for identified --- =>確認飛行物体;略:IFO Overview of verb identify The verb identify has 6 senses (first 6 from tagged texts) 1. (32) identify, place -- (recognize as being; establish the identity of someone or something; "She identified the man on the 'wanted' poster") 2. (7) name, identify -- (give the name or identifying characteristics of; refer to by name or some other identifying characteristic property; "Many senators were named in connection with the scandal"; "The almanac identifies the auspicious months") 3. (6) identify -- (consider (oneself) as similar to somebody else; "He identified with the refugees") 4. (4) identify -- (conceive of as united or associated; "Sex activity is closely identified with the hypothalamus") 5. (2) identify, discover, key, key out, distinguish, describe, name -- (identify as in botany or biology, for example) 6. (2) identify -- (consider to be equal or the same; "He identified his brother as one of the fugitives") Overview of adj identified The adj identified has 1 sense (first 1 from tagged texts) 1. (1) identified -- (having the identity known or established; "the identified bodies were released for burial") --- WordNet end ---