IGF-1 and Its Receptor in Esophageal Cancer: Association with Adenocarcinoma and Visceral Obesity

Doyle, Suzanne; Donohoe, Claire L.; Finn, Stephen P.; Howard, Julia; Lithander, Fiona E; Reynolds, John V.; Pidgeon, Graham P.; Lysaght, Joanne

doi:10.1038/ajg.2011.417

Cited by 99 publications

(79 citation statements)

References 42 publications

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“…Only a few studies have investigated head and neck cancer and IGF-1 association (Doyle et al, 2012;Brady et al, 2007) It has been reported that patients with head and neck cancer that developed second primary tumors have high levels of IGF-1 and low levels of IGFBP-3, so these markers (IGF1/IGFBP-3) represent positive risk factors (Wu et al, 2004). On the contrary, Brady et al showed that circulating levels of both IGF1 and IGFBP3 protein are decreased in head and neck cancer patients (Brady et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Usefulness of IGF-1 serum levels as diagnostic marker of nasopharyngeal carcinoma

et al. 2016

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Section: Introductionmentioning

confidence: 99%

Usefulness of IGF-1 serum levels as diagnostic marker of nasopharyngeal carcinoma

et al. 2016

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“…Although overexpression of IGF-IR and the association between its expression and patients' survival have been reported in various human solid tumors81314, to our knowledge, controversies still exist with expression of IGF-1R as a prognostic factor in ESCC183132. Using banked esophageal tissues from a well-characterized series of patients who underwent complete surgical resection and subsequent standard comprehensive therapy for ESCC, we evaluated expression levels of IGF-IR with immunohistochemical staining.…”

Section: Discussionmentioning

confidence: 99%

Antitumor effects and molecular mechanisms of figitumumab, a humanized monoclonal antibody to IGF-1 receptor, in esophageal carcinoma

Zhang

Shen

Wang

et al. 2014

Sci Rep

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The insulin-like growth factor type 1 receptor (IGF-1R) plays an essential role in the development of numerous cancers. Figitumumab (CP) is not only a monocloncal antibody, it also has agonist activity on IGF-1R. The antitumor activity of CP in esophageal squamous cell carcinoma (ESCC) is still unclear. In our study, we identified IGF-1R as an independent prognostic factor in ESCC patients, and investigated the antitumor effects of CP in ESCC cell lines. CP suppressed tumor growth and sensitized cells to chemotherapeutic drugs. In addition, CP inhibited cell proliferation, migration, colony forming activity and anti-apoptosis induced by IGF-1. Our results showed that CP not only inhibited IGF-1 induced receptor autophosphorylation and downstream signaling, but also triggered β-arrestin1 and G protein-coupled receptor kinases (GRKs) mediated ERK1/2 activation, indicating CP as a biased agonist for IGF-1R. Inhibition of ERK1/2 enhanced the antitumor activity of CP. Furthermore, CP was a more powerful agonist for IGF-1R down-regulation than IGF-1, and dysregulation of β-arrestin1 and GRKs affected this down-regulation. Thus, we demonstrated antitumor activities of CP on ESCC, and as a biased agonist, CP induced ERK1/2 activation and receptor down-regulation required β-arrestin1 and GRKs, suggesting a promising role for targeting IGF-1R in ESCC.

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“…However, adjustment for BMI showed no increase in risk (25). In addition, visceral fat is metabolically active, secreting a number of adipokines, cytokines, and growth factors that may cause the esophageal inflammation leading to carcinogenesis (12,14). Moreover, VFA has been shown to be a prognostic factor in other gastrointestinal malignancies including: colorectal, gastric, and pancreatic cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Epidemiological evidence has identified a positive correlation between various measures of obesity and increasing risk for EA, with one recent meta-analysis showing a 3X increase risk associated with body mass index (BMI) ≥30 kg/m² (7,11,12). Obesity, moreover, is thought to be a prognostic factor in addition to a risk factor for EA (13).…”

Section: Introductionmentioning

confidence: 99%

CT-based assessment of visceral adiposity and outcomes for esophageal adenocarcinoma

Saeed¹,

Shridhar²,

Almhanna³

et al. 2017

J. Gastrointest. Oncol.

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Background: Various methods of quantifying and correlating obesity to outcomes for patients with esophageal adenocarcinoma (EA) have been evaluated. Published data suggest that quantification of adiposity may be more accurate than body mass index (BMI) as a prognostic factor. We report our analysis of adiposity as a prognostic factor in a series of patients with EA. to −130. Outcomes were analyzed using Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was performed using the Cox proportion hazard regression model. Results:We identified 126 patients for the analysis. There were no statistically significant differences in overall survival or disease-free survival between groups above and below the medians for TFA, SFA, or VFA/SFA ratio. However, an increase in VFA was significantly associated with worsened OS and DFS when we further classified patients into quartiles. Patients with VFA ≥182 cm² had larger tumor size (P=0.016), fewer involved lymph nodes (P=0.047), longer operating times (P=0.032), and were more likely to be males (P=0.042).Conclusions: Published data have demonstrated an association between treatment outcomes and degree of adiposity; our study found a correlation between VFA and OS and DFS in patients with EA. Median TFA, SFA, and VFA/SFA were not prognostic on MVA. While VFA >182 cm 2 was associated with larger tumors, there were also fewer lymph nodes harvested in this group.

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IGF-1 and Its Receptor in Esophageal Cancer: Association with Adenocarcinoma and Visceral Obesity

Cited by 99 publications

References 42 publications

Usefulness of IGF-1 serum levels as diagnostic marker of nasopharyngeal carcinoma

Usefulness of IGF-1 serum levels as diagnostic marker of nasopharyngeal carcinoma

Antitumor effects and molecular mechanisms of figitumumab, a humanized monoclonal antibody to IGF-1 receptor, in esophageal carcinoma

CT-based assessment of visceral adiposity and outcomes for esophageal adenocarcinoma

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