scholarly journals Transgelin is a poor prognostic factor associated with advanced colorectal cancer (CRC) stage promoting tumor growth and migration in a TGFβ-dependent manner

2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Mona Elsafadi ◽  
Muthurangan Manikandan ◽  
Sami Almalki ◽  
Amer Mahmood ◽  
Tasneem Shinwari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Tumor Growth ◽  
Advanced Colorectal Cancer ◽  
Dependent Manner ◽  
Poor Prognostic Factor ◽  
And Migration

KRASandBRAFMutations in Advanced Colorectal Cancer Are Associated With Poor Prognosis but Do Not Preclude Benefit From Oxaliplatin or Irinotecan: Results From the MRC FOCUS Trial

2009 ◽  
Vol 27 (35) ◽  
pp. 5931-5937 ◽  
Author(s):  
Susan D. Richman ◽  
Matthew T. Seymour ◽  
Philip Chambers ◽  
Faye Elliott ◽  
Catherine L. Daly ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Braf Mutation ◽  
Poor Prognosis ◽  
Advanced Colorectal Cancer ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Poor Prognostic Factor ◽  
Minimal Impact ◽  
The Impact

PurposeActivating mutation of the KRAS oncogene is an established predictive biomarker for resistance to anti–epidermal growth factor receptor (anti-EGFR) therapies in advanced colorectal cancer (aCRC). We wanted to determine whether KRAS and/or BRAF mutation is also a predictive biomarker for other aCRC therapies.Patients and MethodsThe Medical Research Council Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing (MRC FOCUS) trial compared treatment sequences including first-line fluorouracil (FU), FU/irinotecan or FU/oxaliplatin in aCRC. Tumor blocks were obtained from 711 consenting patients. DNA was extracted and KRAS codons 12, 13, and 61 and BRAF codon 600 were assessed by pyrosequencing. Mutation (mut) status was assessed first as a prognostic factor and then as a predictive biomarker for the benefit of adding irinotecan or oxaliplatin to FU. The association of BRAF-mut with loss of MLH1 was assessed by immunohistochemistry.ResultsThree hundred eight (43.3%) of 711 patients had KRAS-mut and 56 (7.9%) of 711 had BRAF-mut. Mutation of KRAS, BRAF, or both was present in 360 (50.6%) of 711 patients. Mutation in either KRAS or BRAF was a poor prognostic factor for overall survival (OS; hazard ratio [HR], 1.40; 95% CI, 1.20 to 1.65; P < .0001) but had minimal impact on progression-free survival (PFS; HR, 1.16; 95% CI, 1.00 to 1.36; P = .05). Mutation status did not affect the impact of irinotecan or oxaliplatin on PFS or OS. BRAF-mut was weakly associated with loss of MLH1 staining (P = .012).ConclusionKRAS/BRAF mutation is associated with poor prognosis but is not a predictive biomarker for irinotecan or oxaliplatin. There is no evidence that patients with KRAS/BRAF mutated tumors are less likely to benefit from these standard chemotherapy agents.

scholarly journals miR-23a-3p is a Key Regulator of IL-17C-Induced Tumor Angiogenesis in Colorectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1363 ◽  
Author(s):  
Yunna Lee ◽  
Su Jin Kim ◽  
Jieun Choo ◽  
Gwangbeom Heo ◽  
Jin-Wook Yoo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Tumor Angiogenesis ◽  
Ex Vivo ◽  
Underlying Mechanism ◽  
Vegf Receptor ◽  
Invasion And Migration ◽  
Novel Target ◽  
And Migration

MicroRNAs (miRNAs) have emerged as key players in tumor angiogenesis. Interleukin-17C (IL-17C) was identified to promote colorectal cancer (CRC) progression. Therefore, we aimed to investigate the effect of IL-17C on tumor angiogenesis, the involvement of miR-23a-3p in IL-17C signaling, and the direct target gene of miR-23a-3p in CRC. In vitro and ex vivo angiogenesis, a mouse xenograft experiment, and immunostaining were performed to test the effect of IL-17C on tumor angiogenesis. ELISA, quantitative real time PCR, and gene silencing were used to uncover the underlying mechanism. IL-17C induced angiogenesis of intestinal endothelial cells, subsequently enhancing cell invasion and migration of DLD-1 cells. IL-17C-stimulated DLD-1 cells produced vascular endothelial growth factor (VEGF) to enhance angiogenesis. Moreover, IL-17C markedly accelerated xenograft tumor growth, which was manifested by substantially reduced tumor growth when treated with the VEGF receptor 2 inhibitor Ki8751. Accordingly, Ki8751 suppressed the expression of IL-17C-stimulated PECAM and VE-cadherin in xenografts. Furthermore, IL-17C activated STAT3 to increase the expression of miR-23a-3p that suppressed semaphorin 6D (SEMA6D) expression, thereby permitting VEGF production. Taken together, our study demonstrates that IL-17C promotes tumor angiogenesis through VEGF production via a STAT3/miR-23a-3p/SEMA6D axis, suggesting its potential as a novel target for anti-CRC therapy.

Preoperative UFT administration for patients with advanced colorectal cancer - increased uptake of 5-fluorouracil by tumor tissue is a prognostic factor

2000 ◽  
Vol 11 (3) ◽  
pp. 155-163 ◽  
Author(s):  
Tohru Nakagoe ◽  
Hiroshi Ishikawa ◽  
Terumitsu Sawai ◽  
Takashi Tsuji ◽  
Hiroyoshi Ayabe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Tumor Tissue ◽  
Advanced Colorectal Cancer

Nobiletin Inhibits Proliferation, Invasion, Migration and Angiogenesis in Colorectal Cancer Cells

2019 ◽  
Vol 9 (5) ◽  
pp. 662-667
Author(s):  
Jing Li ◽  
Zaijun Li ◽  
Fei Zheng
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Invasion ◽  
Human Cancer ◽  
Cell Counting ◽  
Control Group ◽  
Dependent Manner ◽  
Invasion And Migration ◽  
Traditional Chinese Herbal Medicine ◽  
And Migration

Aim/Background: The nobiletin is a polymethoxyflavonoid isolated from citrus, which is a traditional Chinese herbal medicine. The nobiletin could inhibit the development of human cancer. However, the role of nobiletin in human colorectal cancer (CRC) remains unknown. The present study aimed to explore the nobiletin function in CRC cell proliferation, migration, invasion and angiogenesis as well as the occurrence mechanisms. Methods: The cell counting kit-8 assay (CCK-8 assay) and Brdu (5-brom-2-odeoxyuridine) staining assay were used to determine the effect of nobiletin on cell proliferation. The transwell assay and wound healing assay were used to assess cell invasion and migration. The western blot analysis was performed to determine the expression of VEGFA, Ang2, p65, p-p65, STAT3, p-STAT3 in CRC cell. Result: Compared with the control group (0 mg/L), the cell proliferation was increased in a dose-dependent manner with 10, 50, 100, 150 mg/L nobiletin for 48 h. The nobiletin inhibited cell invasion and migration and suppressed the expression of VEGFA and Ang2 to block angiogenesis in the colorectal cancer. In addition, we found that nobiletin inhibited cell proliferation, invasion, migration and angiogenesis by suppression of NF-κB/STAT3 pathway. Conclusion: The study provided evidence that nobiletin inhibited cell proliferation, invasion, migration and angiogenesis in the colorectal cancer.

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