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return kwic search for growth out of >500 occurrences
309169 occurrences (No.70 in the rank) during 5 years in the PubMed. [no cache] 500 found

212) In vivo, Hhat knockdown led to reduction of tumor growth in a mouse xenograft model of pancreatic cancer.

--- ABSTRACT ---

PMID:24469057 DOI:10.1038/onc.2013.575

2015 Oncogene

* Hedgehog acyltransferase as a target in pancreatic ductal adenocarcinoma.

- Sonic Hedgehog (Shh) is abnormally expressed in pancreatic cancer and is associated with disease onset and progression. Inhibition of Shh signaling is thus an attractive clinical target for therapeutic intervention. Most efforts to block Shh signaling have focused on inhibitors of Smoothened, which target the canonical Shh signaling pathway. These approaches have met with limited success, in part due to development of resistance-conferring mutations and contributions from non-canonical signaling pathways. Here, we show that Hedgehog acyltransferase (Hhat), the enzyme responsible for the attachment of palmitate onto Shh, is a novel target for inhibition of Shh signaling in pancreatic cancer cells. Depletion of Hhat with lentivirally delivered small hairpin RNA decreased both anchorage-dependent and independent proliferation of human pancreatic cancer cells. In vivo, Hhat knockdown led to reduction of tumor growth in a mouse xenograft model of pancreatic cancer. RU-SKI 43, a small molecule inhibitor of Hhat recently developed by our group, reduced pancreatic cancer cell proliferation and Gli-1 activation through Smoothened-independent non-canonical signaling. In addition, RU-SKI 43 treatment inhibited two key proliferative pathways regulated by Akt and mTOR. This work demonstrates that Hhat has a critical role in pancreatic cancer and that a small molecule inhibitor of Hhat can successfully block pancreatic cancer cell proliferation. It also highlights the importance of developing optimized Hhat inhibitors to be used as therapeutics in pancreatic cancer, as well as in other malignancies characterized by Shh overexpression.

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[frequency of next (right) word to growth]

(1)69 and	(12)5 at	(25)3 models	(36)2 model
(2)48 factor	(13)4 but	(26)3 or	(37)2 modeling
(3)48 of	(14)4 during	(27)3 traits	(38)2 outcomes
(4)41 null	(15)4 factor,	(28)3 trajectories	(39)2 phase
(5)32 in	(17)4 patterns	(29)2 among	(40)2 properties
(6)25 factors	(18)4 plate	(30)2 are	(41)2 responses
(7)9 inhibition	(19)4 response	(31)2 as	(42)2 restriction
(8)8 rate	(20)4 was	(32)2 dynamics	(43)2 stunting
(9)6 factors,	(21)3 cone	(33)2 effects	(44)2 to
(10)6 rates	(22)3 curve	(34)2 forest	(45)2 velocities
(11)5 arrest	(23)3 factor-C	(35)2 hormone	(46)2 were

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--- WordNet output for growth --- =>茂み, 成長, 増加, 発展, 栽培, 腫よう, 成長物 Overview of noun growth The noun growth has 7 senses (first 5 from tagged texts) 1. (37) growth, growing, maturation, development, ontogeny, ontogenesis -- ((biology) the process of an individual organism growing organically; a purely biological unfolding of events involved in an organism changing gradually from a simple to a more complex level; "he proposed an indicator of osseous development in children") 2. (20) growth -- (a progression from simpler to more complex forms; "the growth of culture") 3. (3) increase, increment, growth -- (a process of becoming larger or longer or more numerous or more important; "the increase in unemployment"; "the growth of population") 4. (3) growth -- (vegetation that has grown; "a growth of trees"; "the only growth was some salt grass") 5. (1) emergence, outgrowth, growth -- (the gradual beginning or coming forth; "figurines presage the emergence of sculpture in Greece") 6. growth -- ((pathology) an abnormal proliferation of tissue (as in a tumor)) 7. growth -- (something grown or growing; "a growth of hair") --- WordNet end ---