ELIZA cgi-bash version rev. 1.90
- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -

return kwic search for further out of >500 occurrences
298283 occurrences (No.79 in the rank) during 5 years in the PubMed. [no cache] 500 found
188) These data are further supported by immunohistochemical analysis of human NSCLC samples showing loss or downregulation of Notch2 compared with normal lung tissue.
--- ABSTRACT ---
PMID:24509876 DOI:10.1038/onc.2013.592
2015 Oncogene
* Opposing role of Notch1 and Notch2 in a Kras(G12D)-driven murine non-small cell lung cancer model.
- Lung cancer is the leading cause of cancer-related deaths worldwide. Recently, we have shown that Notch1 inhibition resulted in substantial cell death of non-small cell lung cancer (NSCLC) cells in vitro. New compounds targeting Notch signal transduction have been developed and are now being tested in clinical trials. However, the tumorigenic role of individual Notch receptors in vivo remains largely unclear. Using a Kras(G12D)-driven endogenous NSCLC mouse model, we analyzed the effect of conditional Notch1 and Notch2 receptor deletion on NSCLC tumorigenesis. Notch1 deficiency led to a reduced early tumor formation and lower activity of MAPK compared with the controls. Unexpectedly, Notch2 deletion resulted in a dramatically increased carcinogenesis and increased MAPK activity. These mice died significantly earlier due to rapidly growing tumor burden. We found that Notch1 regulates Ras/MAPK pathway via HES1-induced repression of the DUSP1 promoter encoding a phosphatase specifically suppressing pERK1/2. Interestingly, Notch1 but not Notch2 ablation leads to decreased HES1 and DUSP1 expression. However, Notch2-depleted tumors showed an appreciable increase in β-catenin expression, a known activator of HES1 and important lung cancer oncogene. Characteristically for β-catenin upregulation, we found that the majority of Notch2-deficient tumors revealed an undifferentiated phenotype as determined by their morphology, E-Cadherin and TTF1 expression levels. In addition, these carcinomas showed aggressive growth patterns with bronchus invasion and obstruction. Together, we show that Notch2 mediates differentiation and has tumor suppressor functions during lung carcinogenesis, whereas Notch1 promotes tumor initiation and progression. These data are further supported by immunohistochemical analysis of human NSCLC samples showing loss or downregulation of Notch2 compared with normal lung tissue. In conclusion, this is the first study characterizing the in vivo functions of Notch1 and Notch2 in Kras(G12D)-driven NSCLC tumorigenesis. These data highlight the clinical importance of a thorough understanding of Notch signaling especially with regard to Notch-targeted therapies.
--- ABSTRACT END ---
[
right
kwic]
[frequency of next (right) word to further]
(1)39 studies (16)4 developed (31)2 analyses (46)2 insights
(2)32 research (17)4 in (32)2 analyzed (47)2 monitoring
(3)18 investigation (18)4 supported (33)2 application (48)2 optimization
(4)18 study (19)3 *null* (34)2 as (49)2 prospective
(5)11 the (20)3 a (35)2 assessed (50)2 protection
(6)10 investigations (21)3 clinical (36)2 complications (51)2 spread
(7)8 analysis (22)3 evaluation (37)2 divided (52)2 suggests
(8)7 evidence (23)3 exploration (38)2 elucidate (53)2 supporting
(9)7 phylogenetic (24)3 explore (39)2 enhance (54)2 supports
(10)6 explored (25)3 for (40)2 episodes (55)2 taxonomic
(11)5 development (26)3 increased (41)2 evaluated (56)2 that
(12)5 support (27)3 investigate (42)2 examination (57)2 used
(13)5 validation (28)3 molecular (43)2 identification
(14)4 by (29)3 understand (44)2 improvement
(15)4 confirmed (30)2 advances (45)2 increase

add keyword

--- WordNet output for further --- =>1.さらにずっと, さらに先に, 一層遠く, その上, 更に, もっと遠い, なお一層の, さらに遠く, もっと先に, いっそうはるかに, さらにまた, さらになお(furthermore), 2.進める, 助成する, 促進する Overview of verb further The verb further has 2 senses (first 2 from tagged texts) 1. (7) foster, further -- (promote the growth of; "Foster our children's well-being and education") 2. (2) promote, advance, boost, further, encourage -- (contribute to the progress or growth of; "I am promoting the use of computers in the classroom") Overview of adj further The adj further has 1 sense (first 1 from tagged texts) 1. (2) further, farther -- (more distant in especially degree; "nothing could be further from the truth"; "further from our expectations"; "farther from the truth"; "farther from our expectations") Overview of adv further The adv further has 3 senses (first 3 from tagged texts) 1. (33) further, farther -- (to or at a greater extent or degree or a more advanced stage (`further' is used more often than `farther' in this abstract sense); "further complicated by uncertainty about the future"; "let's not discuss it further"; "nothing could be further from the truth"; "they are further along in their research than we expected"; "the application of the law was extended farther"; "he is going no farther in his studies") 2. (10) further -- (in addition or furthermore; "if we further suppose"; "stated further that he would not cooperate with them"; "they are definitely coming; further, they should be here already") 3. (1) farther, further -- (to or at a greater distance in time or space (`farther' is used more frequently than `further' in this physical sense); "farther north"; "moved farther away"; "farther down the corridor"; "the practice may go back still farther to the Druids"; "went only three miles further"; "further in the future") Overview of adv far The adv far has 5 senses (first 4 from tagged texts) 1. (61) far -- (to a considerable degree; very much; "a far far better thing that I do"; "felt far worse than yesterday"; "eyes far too close together") 2. (39) far -- (at or to or from a great distance in space; "he traveled far"; "strayed far from home"; "sat far away from each other") 3. (22) far -- (at or to a certain point or degree; "I can only go so far before I have to give up"; "how far can we get with this kind of argument?") 4. (3) far -- (remote in time; "if we could see far into the future"; "all that happened far in the past") 5. far -- (to an advanced stage or point; "a young man who will go very far") --- WordNet end ---