ELIZA

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296134 occurrences (No.80 in the rank) during 5 years in the PubMed. [no cache] 500 found

372) 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.

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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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(1)187 of	(14)3 adhesive	(27)2 BGP	(40)2 organic
(2)21 length	(15)3 annual	(28)2 DNA,	(41)2 oxidant
(3)13 number	(16)3 delivered	(29)2 activity	(42)2 pleural
(4)7 antioxidant	(17)3 knee	(30)2 arch	(43)2 protein,
(5)7 protein	(18)3 length,	(31)2 biomass	(44)2 repetitions
(6)5 body	(19)3 optical	(32)2 collagen	(45)2 scores
(7)5 cholesterol	(20)3 or	(33)2 daily	(46)2 snack
(8)5 dose	(21)3 parenteral	(34)2 dietary	(47)2 soluble
(9)5 score	(22)3 polyphenols	(35)2 exercise	(48)2 stress
(10)4 HG	(23)3 population	(36)2 genome	(49)2 tumor
(11)4 amount	(24)3 sample	(37)2 health-care	(50)2 volume
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(13)4 cell	(26)2 248	(39)2 mitochondrial

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--- WordNet output for total --- =>1.(車が)全壊する, 全損する, 2.全体の, 全ての, 総計の, 総体の, 全くの, 完全な, 総力の, 3.総額, 総計, 全体の, (車が)全壊する, 合計(する), なる Overview of noun total The noun total has 2 senses (first 2 from tagged texts) 1. (13) sum, total, totality, aggregate -- (the whole amount) 2. (6) sum, amount, total -- (a quantity obtained by the addition of a group of numbers) Overview of verb total The verb total has 3 senses (first 2 from tagged texts) 1. (16) total, number, add up, come, amount -- (add up in number or quantity; "The bills amounted to $2,000"; "The bill came to $2,000") 2. (2) total, tot, tot up, sum, sum up, summate, tote up, add, add together, tally, add up -- (determine the sum of; "Add all the people in this town to those of the neighboring town") 3. total -- (damage beyond the point of repair; "My son totaled our new car"; "the rock star totals his guitar at every concert") Overview of adj total The adj total has 2 senses (first 2 from tagged texts) 1. (31) entire, full, total -- (constituting the full quantity or extent; complete; "an entire town devastated by an earthquake"; "gave full attention"; "a total failure") 2. (2) full, total -- (complete in extent or degree and in every particular; "a full game"; "a total eclipse"; "a total disaster") --- WordNet end ---