ELIZA

return kwic search for response out of >500 occurrences
343831 occurrences (No.54 in the rank) during 5 years in the PubMed. [no cache] 500 found

371) 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.

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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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(1)146 to	(14)4 proteins	(27)3 time	(40)2 following
(2)32 null	(15)4 rates	(28)3 times	(41)2 from
(3)31 and	(16)4 that	(29)3 which	(42)2 including
(4)22 of	(17)4 the	(30)2 (ABR)	(43)2 latency
(5)21 rate	(18)3 at	(31)2 (DDR)	(44)2 mediated
(6)14 was	(19)3 during	(32)2 (UPR)	(45)2 or
(7)13 in	(20)3 elements	(33)2 after	(46)2 rate)
(8)8 selection	(21)3 models	(34)2 are	(47)2 rates,
(9)7 surface	(22)3 options	(35)2 boundaries	(48)2 such
(10)6 data	(23)3 properties	(36)2 delays	(49)2 theory
(11)6 is	(24)3 strategies	(37)2 effects	(50)2 validity
(12)4 for	(25)3 style	(38)2 element	(51)2 were
(13)4 patterns	(26)3 suppression	(39)2 evaluation

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--- WordNet output for response --- =>反応, 応答, 返答, 返報, 反響, 答唱句 Overview of noun response The noun response has 7 senses (first 5 from tagged texts) 1. (11) response -- (a result; "this situation developed in response to events in Africa") 2. (11) reaction, response -- (a bodily process occurring due to the effect of some antecedent stimulus or agent; "a bad reaction to the medicine"; "his responses have slowed with age") 3. (6) answer, reply, response -- (a statement (either spoken or written) that is made to reply to a question or request or criticism or accusation; "I waited several days for his answer"; "he wrote replies to several of his critics") 4. (4) reception, response -- (the manner in which something is greeted; "she did not expect the cold reception she received from her superiors") 5. (1) response -- (a phrase recited or sung by the congregation following a versicle by the priest or minister) 6. reply, response -- (the speech act of continuing a conversational exchange; "he growled his reply") 7. response -- (the manner in which an electrical or mechanical device responds to an input signal or a range of input signals) --- WordNet end ---