Increased expression of IGF-1Ec with increasing colonic polyp dysplasia and colorectal cancer

Alagaratnam, Swethan; Loizidou, Marilena; Yang, Shi Yu; Fuller, Barry; Ramesh, Bala

doi:10.1007/s00432-020-03345-0

Cited by 8 publications

(6 citation statements)

References 36 publications

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“…Alagaratnam S et al detected IGF-1Ec, an isoform of IGF-1, in 16 patients with CRC and 11 patients with colonic polyp. IGF-1EC has been identified to be overexpressed in cancers, such as prostate and neuroendocrine tumors [ 113 ]. The study revealed a significantly increased expression of IGF-1Ec in CRC patients ( p < 0.001) and colorectal polyps ( p < 0.05) compared with normal colonic tissues [ 113 ].…”

Section: Crc Pathogenesismentioning

confidence: 99%

“…IGF-1EC has been identified to be overexpressed in cancers, such as prostate and neuroendocrine tumors [ 113 ]. The study revealed a significantly increased expression of IGF-1Ec in CRC patients ( p < 0.001) and colorectal polyps ( p < 0.05) compared with normal colonic tissues [ 113 ]. Furthermore, it has been postulated that markers of hyperinsulinemia such as IGF-1 and C-peptide may be correlated with an increased risk of CRC [ 114 ].…”

Section: Crc Pathogenesismentioning

confidence: 99%

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Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

Ştefani¹,

Miricescu

Stănescu-Spînu

et al. 2021

IJMS

161

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Colorectal cancer (CRC) is a predominant malignancy worldwide, being the fourth most common cause of mortality and morbidity. The CRC incidence in adolescents, young adults, and adult populations is increasing every year. In the pathogenesis of CRC, various factors are involved including diet, sedentary life, smoking, excessive alcohol consumption, obesity, gut microbiota, diabetes, and genetic mutations. The CRC tumor microenvironment (TME) involves the complex cooperation between tumoral cells with stroma, immune, and endothelial cells. Cytokines and several growth factors (GFs) will sustain CRC cell proliferation, survival, motility, and invasion. Epidermal growth factor receptor (EGFR), Insulin-like growth factor -1 receptor (IGF-1R), and Vascular Endothelial Growth Factor -A (VEGF-A) are overexpressed in various human cancers including CRC. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and all the three major subfamilies of the mitogen-activated protein kinase (MAPK) signaling pathways may be activated by GFs and will further play key roles in CRC development. The main aim of this review is to present the CRC incidence, risk factors, pathogenesis, and the impact of GFs during its development. Moreover, the article describes the relationship between EGF, IGF, VEGF, GFs inhibitors, PI3K/AKT/mTOR-MAPK signaling pathways, and CRC.

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Section: Crc Pathogenesismentioning

confidence: 99%

Section: Crc Pathogenesismentioning

confidence: 99%

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

Ştefani¹,

Miricescu

Stănescu-Spînu

et al. 2021

IJMS

161

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“…Semi-quantitative image analysis was performed with the open-source software ImageJ, and the IHC profiler plug-in developed by Varghese et al [34]. Software operation and data collection were performed as previously described by Alagaratnam et al [35].…”

Section: Colonic Muc2 Detection Using Immunofluorescence and Ihc Stai...mentioning

confidence: 99%

Multi-omics reveal mechanisms of high enteral starch diet mediated colonic dysbiosis via microbiome-host interactions in young ruminant

Jin,

Wu,

Liang

et al. 2024

Microbiome

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Background Although rumen development is crucial, hindgut undertakes a significant role in young ruminants’ physiological development. High-starch diet is usually used to accelerate rumen development for young ruminants, but always leading to the enteral starch overload and hindgut dysbiosis. However, the mechanism behind remains unclear. The combination of colonic transcriptome, colonic luminal metabolome, and metagenome together with histological analysis was conducted using a goat model, with the aim to identify the potential molecular mechanisms behind the disrupted hindgut homeostasis by overload starch in young ruminants. Result Compared with low enteral starch diet (LES), high enteral starch diet (HES)-fed goats had significantly higher colonic pathology scores, and serum diamine oxidase activity, and meanwhile significantly decreased colonic mucosal Mucin-2 (MUC2) protein expression and fecal scores, evidencing the HES-triggered colonic systemic inflammation. The bacterial taxa Prevotella sp. P4-67, Prevotella sp. PINT, and Bacteroides sp. CAG:927, together with fungal taxa Fusarium vanettenii, Neocallimastix californiae, Fusarium sp. AF-8, Hypoxylon sp. EC38, and Fusarium pseudograminearum, and the involved microbial immune pathways including the “T cell receptor signaling pathway” were higher in the colon of HES goats. The integrated metagenome and host transcriptome analysis revealed that these taxa were associated with enhanced pathogenic ability, antigen processing and presentation, and stimulated T helper 2 cell (TH2)-mediated cytokine secretion functions in the colon of HES goats. Further luminal metabolomics analysis showed increased relative content of chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), and decreased the relative content of hypoxanthine in colonic digesta of HES goats. These altered metabolites contributed to enhancing the expression of TH2-mediated inflammatory-related cytokine secretion including GATA Binding Protein 3 (GATA3), IL-5, and IL-13. Using the linear mixed effect model, the variation of MUC2 biosynthesis explained by the colonic bacteria, bacterial functions, fungi, fungal functions, and metabolites were 21.92, 20.76, 19.43, 12.08, and 44.22%, respectively. The variation of pathology scores explained by the colonic bacterial functions, fungal functions, and metabolites were 15.35, 17.61, and 57.06%. Conclusions Our findings revealed that enteral starch overload can trigger interrupted hindgut host-microbiome homeostasis that led to impaired mucosal, destroyed colonic water absorption, and TH2-mediated inflammatory process. Except for the colonic metabolites mostly contribute to the impaired mucosa, the nonnegligible contribution from fungi deserves more future studies focused on the fungal functions in hindgut dysbiosis of young ruminants.

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“…CRCME is immunologically active in which a variety of immune cells are infiltrated, and different tumor-associated antigens (TAA) and tumor-specific antigens (TSA) are expressed. Besides, numerous molecular markers and receptors such as VEGF, EGFR, insulin-like growth factor-1 receptor (IGF-1R), human epidermal growth factor receptor-2 (HER2), integrins, mucin 5AC (MUC5AC), death receptor-5 (DR5), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD1) are overexpressed in the CRCME (35)(36)(37)(38)(39)(40)(41)(42)(43). Hence, immunotherapy targeting these molecules could be a promising therapeutic candidate for CRC treatment (18).…”

Section: Crc Microenvironmentmentioning

confidence: 99%

Personalized Immunotherapy in Colorectal Cancers: Where Do We Stand?

Lan

Huang

et al. 2021

Front. Oncol.

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Colorectal cancer (CRC) is the second leading cause of cancer death in the world. Immunotherapy using monoclonal antibodies, immune-checkpoint inhibitors, adoptive cell therapy, and cancer vaccines has raised great hopes for treating poor prognosis metastatic CRCs that are resistant to the conventional therapies. However, high inter-tumor and intra-tumor heterogeneity hinder the success of immunotherapy in CRC. Patients with a similar tumor phenotype respond differently to the same immunotherapy regimen. Mutation-based classification, molecular subtyping, and immunoscoring of CRCs facilitated the multi-aspect grouping of CRC patients and improved immunotherapy. Personalized immunotherapy using tumor-specific neoantigens provides the opportunity to consider each patient as an independent group deserving of individualized immunotherapy. In the recent decade, the development of sequencing and multi-omics techniques has helped us classify patients more precisely. The expansion of such advanced techniques along with the neoantigen-based immunotherapy could herald a new era in treating heterogeneous tumors such as CRC. In this review article, we provided the latest findings in immunotherapy of CRC. We elaborated on the heterogeneity of CRC patients as a bottleneck of CRC immunotherapy and reviewed the latest advances in personalized immunotherapy to overcome CRC heterogeneity.

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Increased expression of IGF-1Ec with increasing colonic polyp dysplasia and colorectal cancer

Cited by 8 publications

References 36 publications

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

Multi-omics reveal mechanisms of high enteral starch diet mediated colonic dysbiosis via microbiome-host interactions in young ruminant

Personalized Immunotherapy in Colorectal Cancers: Where Do We Stand?

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