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return kwic search for demonstrated out of >500 occurrences
286534 occurrences (No.87 in the rank) during 5 years in the PubMed. [no cache] 500 found

219) CPT-11 demonstrated a dose- and time-dependent inhibition of cell growth, induction of apoptosis, and cell-cycle arrest at G0/G1 phase in HL-60 cells.

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PMID:24474168 DOI:10.1002/tox.21959

2015 Environmental toxicology

* Antitumor effects with apoptotic death in human promyelocytic leukemia HL-60 cells and suppression of leukemia xenograft tumor growth by irinotecan HCl.

- Irinotecan HCl (CPT-11) is an anticancer prodrug, but there is no available information addressing CPT-11-inhibited leukemia cells in in vitro and in vivo studies. Therefore, we investigated the cytotoxic effects of CPT-11 in promyelocytic leukemia HL-60 cells and in vivo and tumor growth in a leukemia xenograft model. Effects of CPT-11 on HL-60 cells were determined using flow cytometry, immunofluorescence staining, comet assay, real-time PCR, and Western blotting. CPT-11 demonstrated a dose- and time-dependent inhibition of cell growth, induction of apoptosis, and cell-cycle arrest at G0/G1 phase in HL-60 cells. CPT-11 promoted the release of AIF from mitochondria and its translocation to the nucleus. Bid, Bax, Apaf-1, caspase-9, AIF, Endo G, caspase-12, ATF-6b, Grp78, CDK2, Chk2, and cyclin D were all significantly upregulated and Bcl-2 was down-regulated by CPT-11 in HL-60 cells. Induction of cell-cycle arrest by CPT-11 was associated with changes in expression of key cell-cycle regulators such as CDK2, Chk2, and cyclin D in HL-60 cells. To test whether CPT-11 could augment antitumor activity in vivo, athymic BALB/c(nu/nu) nude mice were inoculated with HL-60 cells, followed by treatment with either CPT-11. The treatments significantly inhibited tumor growth and reduced tumor weight and volume in the HL-60 xenograft mice. The present study demonstrates the schedule-dependent antileukemia effect of CPT-11 using both in vitro and in vivo models. CPT-11 could potentially be a promising agent for the treatment of promyelocytic leukemia and requires further investigation.

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(1)158 that	(10)5 good	(19)3 excellent	(28)2 efficacy
(2)48 the	(11)5 increased	(20)3 more	(29)2 greater
(3)40 a	(12)5 significantly	(21)3 no	(30)2 how
(4)23 by	(13)4 as	(22)3 that,	(31)2 successful
(5)21 to	(14)4 better	(23)2 acceptable	(32)2 through
(6)13 in	(15)4 improved	(24)2 and	(33)2 using
(7)12 null	(16)4 its	(25)2 both
(8)11 an	(17)4 similar	(26)2 decreased
(9)8 for	(18)3 between	(27)2 differential

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--- WordNet output for demonstrated --- Overview of verb demonstrate The verb demonstrate has 4 senses (first 4 from tagged texts) 1. (24) show, demo, exhibit, present, demonstrate -- (give an exhibition of to an interested audience; "She shows her dogs frequently"; "We will demo the new software in Washington") 2. (22) prove, demonstrate, establish, show, shew -- (establish the validity of something, as by an example, explanation or experiment; "The experiment demonstrated the instability of the compound"; "The mathematician showed the validity of the conjecture") 3. (2) attest, certify, manifest, demonstrate, evidence -- (provide evidence for; stand as proof of; show by one's behavior, attitude, or external attributes; "His high fever attested to his illness"; "The buildings in Rome manifest a high level of architectural sophistication"; "This decision demonstrates his sense of fairness") 4. (1) demonstrate, march -- (march in protest; take part in a demonstration; "Thousands demonstrated against globalization during the meeting of the most powerful economic nations in Seattle") Overview of adj demonstrated The adj demonstrated has 1 sense (first 1 from tagged texts) 1. (1) demonstrated -- (having been demonstrated or verified beyond doubt) --- WordNet end ---