The Potential Role of TGFβ1, TGFβ2 and TGFβ3 Protein Expression in Colorectal Carcinomas

Tsamandas, Athanassios C.; Kardamakis, Dimitrios; Ravazoula, Panagiota; Zolota, Vassiliki; Salakou, Stavroula; Tepetes, Konstantinos; Kalogeropoulou, C.; Tsota, Irene; Kourelis, Theodore; Makatsoris, Thomas; Karavias, Dionissios; Scopa, Chrisoula D.; Bonikos, Dionysis S.; Kalofonos, Haralabos P.; Petsas, Theodore

doi:10.1007/s00066-004-1149-x

Cited by 35 publications

(11 citation statements)

References 27 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TGFα and TGFβ 1 are autocrine/paracrine growth factors classically thought of as potent promoters and inhibitors of growth, respectively [47]. However, many cancer tissues are resistant to TGFβ 1 [47], TGFβ 1 was found to have contextually-related tumor suppressor and pro-oncogenic activities [48, 49], and a variety of cancers [50–52], including colon cancer [50, 52], over express it. TGFα acts through the EGF receptor, TGFβ 1 acts through the TGFβ receptor (TGFβ R), and both receptors are abundantly expressed in the normal colon epithelium [47].…”

Section: 0 Modifiable Molecular Phenotypic Pre-neoplastic Biomarkementioning

confidence: 99%

Effects of supplemental vitamin D and calcium on normal colon tissue and circulating biomarkers of risk for colorectal neoplasms

Bostick

2015

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

This brief review, based on an invited presentation at the 17th Workshop on Vitamin D, is to summarize a line of the author’s research that has been directed at the intertwined missions of clarifying and/or developing vitamin D and calcium and as preventive agents against colorectal cancer in humans, understanding the mechanisms by which these agents may reduce risk for the disease, and developing ‘treatable’ biomarkers of risk for colorectal cancer. The biological plausibility and observational and clinical trial evidence for vitamin D and calcium in reducing risk for colorectal neoplasms, the development of pre-neoplastic biomarkers of risk for colorectal neoplasms, and the clinical trial findings from the author’s research group on the efficacy of vitamin D and calcium in modulating these biomarkers are summarized. Regarding the latter, we tested the efficacy of 800 IU (20 µg) of vitamin D3 and 2.0g of calcium daily, alone and combined vs. placebo over 6 months on modulating normal colon tissue and circulating hypothesis-based biomarkers of risk for colorectal neoplasms in a randomized, double-blind, placebo-controlled, 2×2 factorial design clinical trial (n = 92). The tissue-based biomarkers were measured in biopsies of normal-appearing rectal mucosa using immunohistochemistry with quantitative image analysis, and a panel of circulating inflammation markers was measured using enzyme-linked immunoassays (ELISA). Statistically significant proportional tissue increases in the vitamin D group relative to the placebo group were found in bax (51%), p21 (141%), APC (48%), E-cadherin (78%), MSH2 (179%), the CaSR (39%), and CYP27B1 (159%). In blood, there was a 77% statistically significant decrease in a summary inflammation z-score. The findings for calcium were similar to those for vitamin D. These findings indicate that supplemental vitamin D3 or calcium can favorably modulate multiple normal colon tissue and circulating hypothesis-based biomarkers of risk for colorectal neoplasms in sporadic colorectal adenoma patients.

show abstract

Section: 0 Modifiable Molecular Phenotypic Pre-neoplastic Biomarkementioning

confidence: 99%

Effects of supplemental vitamin D and calcium on normal colon tissue and circulating biomarkers of risk for colorectal neoplasms

Bostick

2015

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

show abstract

“…Of the 8 studies, 6 directly reported the HRs, while the other 3 studies provided survival curves. Three studies identified high expression of TGF-β as an indicator of poor prognosis in terms of OS [13, 16, 21], whereas others showed no significant difference. Seven studies reported the prognostic value of TGF-β for DFS in CRC patients (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…Eight studies that focused on the relationship of TGF-β expression to overall survival of CRC patients undergoing surgery were included in the meta-analysis [10, 13, 15, 16, 21, 24–26]. The combined HR value of the 8 studies that evaluated the high expression of TGF-β with respect to OS was 1.68 (95% CI: 1.10–2.59, Table 3, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Seven studies on TGF-β and DFS in CRC patients undergoing surgery were included in the meta-analysis [16, 17, 22, 25–28]. The combined HR of the 7 studies that evaluated the relationship of the high expression of TGF-β to DFS was 1.11 (95% CI: 1.03–1.19, Table 3, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Some studies demonstrated that high expression of TGF-β was associated with worse survival of patients with CRC [15, 16] whereas some studies failed to show any statistically significant association between high expression of TGF-β and survival in patients with CRC [10, 17]. Thus, it is unclear whether high expression of TGF-β is associated with worse survival in CRC patients.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prognostic value of transforming growth factor-beta in patients with colorectal cancer who undergo surgery: a meta-analysis

Chen

Zhu

et al. 2017

BMC Cancer

View full text Add to dashboard Cite

BackgroundTransforming growth factor-beta (TGF-β) is associated with a higher incidence of distant metastasis and decreased survival. Whether TGF-β can be used as a prognostic indicator of colorectal cancer (CRC) remains controversial.MethodsThe Medline, EMBASE and Cochrane databases were searched from their inception to March 2016. The studies that focused on TGF-β as a prognostic factor in patients with CRC were included in this analysis. Overall survival (OS) and disease-free survival (DFS) were analysed separately. A meta-analysis was performed, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated.ResultsTwelve studies were included in the analysis, of which 8 were used for OS and 7 for DFS. In all, 1622 patients with CRC undergoing surgery were included. Combined HRs suggested that high expression of TGF-β had a favourable impact on OS (HR = 1.68, 95% CI: 1.10–2.59) and DFS (HR = 1.11, 95% CI: 1.03–1.19) in CRC patients. For OS, the combined HRs of Asian studies and Western studies were 1.50 (95% CI: 0.61–3.68) and 1.80 (95% CI: 1.33–2.45), respectively. For DFS, the combined HRs of Asian studies and Western studies were 1.42 (95% CI: 0.61–3.31) and 1.11 (95% CI: 1.03–1.20), respectively.ConclusionsThis meta-analysis demonstrates that TGF-β can be used as a prognostic biomarker for CRC patients undergoing surgery, especially for CRC patients from Western countries.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3215-7) contains supplementary material, which is available to authorized users.

show abstract

Genetic variation in the transforming growth factor‐β signaling pathway and survival after diagnosis with colon and rectal cancer

Slattery

Lundgreen

Herrick

et al. 2011

Cancer

View full text Add to dashboard Cite

BACKGROUND The transforming growth factor-β (TGF-β) signaling pathway is involved in many aspects of tumori-genesis, including angiogenesis and metastasis. The authors evaluated this pathway in association with survival after a diagnosis of colon or rectal cancer. METHODS The study included 1553 patients with colon cancer and 754 patients with rectal cancer who had incident first primary disease and were followed for a minimum of 7 years after diagnosis. Genetic variations were evaluated in the genes TGF-β1 (2 single nucleotide polymorphisms [SNPs]), TGF-β receptor 1 (TGF-βR1) (3 SNPs), smooth muscle actin/mothers against decapentaplegic homolog 1 (Smad1) (5 SNPs), Smad2 (4 SNPs), Smad3 (37 SNPs), Smad4 (2 SNPs), Smad7 (11 SNPs), bone morphogenetic protein 1 (BMP1) (11 SNPs), BMP2 (5 SNPs), BMP4 (3 SNPs), bone morphogenetic protein receptor 1A (BMPR1A) (9 SNPs), BMPR1B (21 SNPs), BMPR2 (11 SNPs), growth differentiation factor 10 (GDF10) (7 SNPs), Runt-related transcription factor 1 (RUNX1) (40 SNPs), RUNX2 (19 SNPs), RUNX3 (9 SNPs), eukaryotic translation initiation factor 4E (eiF4E) (3 SNPs), eukaryotic translation initiation factor 4E-binding protein 3 (eiF4EBP2) (2 SNPs), eiF4EBP3 (2 SNPs), and mitogen-activated protein kinase 1 (MAPK1) (6 SNPs). RESULTS After adjusting for American Joint Committee on Cancer stage and tumor molecular phenotype, 12 genes and 18 SNPs were associated with survival in patients with colon cancer, and 7 genes and 15 tagSNPs were associated with survival after a diagnosis of rectal cancer. A summary score based on “at-risk” genotypes revealed a hazard rate ratio of 5.10 (95% confidence interval, 2.56-10.15) for the group with the greatest number of “at-risk” genotypes; for rectal cancer, the hazard rate ratio was 6.03 (95% confidence interval, 2.83-12.75). CONCLUSIONS The current findings suggest that the presence of several higher risk alleles in the TGF-β signaling pathway increase the likelihood of dying after a diagnosis of colon or rectal cancer.

show abstract

The Potential Role of TGFβ1, TGFβ2 and TGFβ3 Protein Expression in Colorectal Carcinomas

Cited by 35 publications

References 27 publications

Effects of supplemental vitamin D and calcium on normal colon tissue and circulating biomarkers of risk for colorectal neoplasms

Effects of supplemental vitamin D and calcium on normal colon tissue and circulating biomarkers of risk for colorectal neoplasms

Prognostic value of transforming growth factor-beta in patients with colorectal cancer who undergo surgery: a meta-analysis

Genetic variation in the transforming growth factor‐β signaling pathway and survival after diagnosis with colon and rectal cancer

Contact Info

Product

Resources

About