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298283 occurrences (No.79 in the rank) during 5 years in the PubMed. [no cache] 500 found

184) Further, in a mouse model transfected CAFs were co-injected with MCF7 and tumour weight and proportion was monitored.

--- ABSTRACT ---

PMID:24336330 DOI:10.1038/onc.2013.527

2015 Oncogene

* TGF-beta receptor type-2 expression in cancer-associated fibroblasts regulates breast cancer cell growth and survival and is a prognostic marker in pre-menopausal breast cancer.

- Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine with the capability to act as tumour suppressor or tumour promoter depending on the cellular context. TGF-beta receptor type-2 (TGFBR2) is the ligand-binding receptor for all members of the TGF-β family. Data from mouse model experiments demonstrated that loss of Tgfbr2 expression in mammary fibroblasts was linked to tumour initiation and metastasis. Using a randomised tamoxifen trial cohort including in total 564 invasive breast carcinomas, we examined TGFBR2 expression (n=252) and phosphorylation level of downstream target SMAD2 (pSMAD2) (n=319) in cancer-associated fibroblasts (CAFs) and assessed links to clinicopathological markers, prognostic and treatment-predictive values. The study revealed that CAF-specific TGFBR2 expression correlated with improved recurrence-free survival. Multivariate analysis confirmed CAF-TGFBR2 to be an independent prognostic marker (multivariate Cox regression, hazard ratio: 0.534, 95% (CI): 0.360-0.793, P=0.002). CAF-specific pSMAD2 levels, however, did not associate with survival outcome. Experimentally, TGF-β signalling in fibroblasts was modulated using a TGF-β ligand and inhibitor or through lentiviral short hairpin RNA-mediated TGFBR2-specific knockdown. To determine the role of fibroblastic TGF-β pathway on breast cancer cells, we used cell contact-dependent cell growth and clonogenicity assays, which showed that knockdown of TGFBR2 in CAFs resulted in increased cell growth, proliferation and clonogenic survival. Further, in a mouse model transfected CAFs were co-injected with MCF7 and tumour weight and proportion was monitored. We found that mouse xenograft tumours comprising TGFBR2 knockdown fibroblasts were slightly bigger and displayed increased tumour cell capacity. Overall, our data demonstrate that fibroblast-related biomarkers possess clinically relevant information and that fibroblasts confer effects on breast cancer cell growth and survival. Regulation of tumour-stromal cross-talk through fibroblastic TGF-β pathway may depend on fibroblast phenotype, emphasising the importance to characterise tumour microenvironment subtypes.

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[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

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--- 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 ---