scholarly journals Flipside of the Coin: Iron Deficiency and Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Aysegül Aksan ◽  
Karima Farrag ◽  
Sami Aksan ◽  
Oliver Schroeder ◽  
Jürgen Stein
Keyword(s):  
Colorectal Cancer ◽  
Iron Deficiency ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Clinical Evidence ◽  
Response To Therapy ◽  
Iron Intake ◽  
Excess Iron ◽  
Tumor Immune Microenvironment ◽  
Cancer Initiation

Iron deficiency, with or without anemia, is the most frequent hematological manifestation in individuals with cancer, and is especially common in patients with colorectal cancer. Iron is a vital micronutrient that plays an essential role in many biological functions, in the context of which it has been found to be intimately linked to cancer biology. To date, however, whereas a large number of studies have comprehensively investigated and reviewed the effects of excess iron on cancer initiation and progression, potential interrelations of iron deficiency with cancer have been largely neglected and are not well-defined. Emerging evidence indicates that reduced iron intake and low systemic iron levels are associated with the pathogenesis of colorectal cancer, suggesting that optimal iron intake must be carefully balanced to avoid both iron deficiency and iron excess. Since iron is vital in the maintenance of immunological functions, insufficient iron availability may enhance oncogenicity by impairing immunosurveillance for neoplastic changes and potentially altering the tumor immune microenvironment. Data from clinical studies support these concepts, showing that iron deficiency is associated with inferior outcomes and reduced response to therapy in patients with colorectal cancer. Here, we elucidate cancer-related effects of iron deficiency, examine preclinical and clinical evidence of its role in tumorigenesis, cancer progression and treatment response. and highlight the importance of adequate iron supplementation to limit these outcomes.

scholarly journals Iron deficiency, immunology, and colorectal cancer

2020 ◽  
Vol 79 (1) ◽  
pp. 88-97
Author(s):  
Oliver Phipps ◽  
Matthew J Brookes ◽  
Hafid O Al-Hassi
Keyword(s):  
Colorectal Cancer ◽  
Iron Deficiency ◽  
Response To Therapy ◽  
Cancer Development ◽  
Iron Therapy ◽  
Iron Intake ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Cancer Immunosurveillance

Abstract Excessive gut luminal iron contributes to the initiation and progression of colorectal cancer. However, emerging evidence suggests that reduced iron intake and low systemic iron levels are also associated with the pathogenesis of colorectal cancer. This is important because patients with colorectal cancer often present with iron deficiency. Iron is necessary for appropriate immunological functions; hence, iron deficiency may hinder cancer immunosurveillance and potentially modify the tumor immune microenvironment, both of which may assist cancer development. This is supported by studies showing that patients with colorectal cancer with iron deficiency have inferior outcomes and reduced response to therapy. Here, we provide an overview of the immunological consequences of iron deficiency and suggest ensuring adequate iron therapy to limit these outcomes.

IRON INTAKE, HEMOGLOBIN, AND PHYSICAL GROWTH DURING THE FIRST TWO YEARS OF LIFE

PEDIATRICS ◽  
1962 ◽  
Vol 30 (4) ◽  
pp. 518-539
Author(s):  
Virginia A. Beal ◽  
Aldula J. Meyers ◽  
Robert W. McCammon
Keyword(s):  
Food Intake ◽  
Iron Deficiency ◽  
Growth Rates ◽  
Rapid Growth ◽  
Clinical Evidence ◽  
Physical Growth ◽  
First Year ◽  
Dietary Iron ◽  
Iron Intake ◽  
Hemoglobin Synthesis

The variety of infant diets given subjects in this group during the first year all provide iron in amounts of 0.5 mg/kg/day or more except in one of the 59 children. This level of dietary iron intake was adequate to meet iron requirements for hemoglobin synthesis and to prevent development of hematologic or clinical evidence of iron deficiency. Food intake adequate to support rapid growth rates contains enough iron to support the needed relative acceleration of hemoglobin synthesis. Lower intakes of iron are associated with higher percentage utilization in hemoglobin synthesis and higher intakes result in lower utilization. Supplementation of diets with iron in several forms occurred in 25% of the group without hematologic evidence of response as compared with the group dependent on dietary iron alone.

scholarly journals Intratumoral Adipocyte-High Breast Cancer Enrich for Metastatic and Inflammation-Related Pathways but Associated with Less Cancer Cell Proliferation

2020 ◽  
Vol 21 (16) ◽  
pp. 5744 ◽  
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Li Yan ◽  
Jing Li Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cancer Biology ◽  
The Cancer Genome Atlas ◽  
Related Gene ◽  
Immune Microenvironment ◽  
Gene Sets ◽  
Tumor Immune Microenvironment ◽  
Er Positive

Cancer-associated adipocytes are known to cause inflammation, leading to cancer progression and metastasis. The clinicopathological and transcriptomic data from 2256 patients with breast cancer were obtained based on three cohorts: The Cancer Genome Atlas (TCGA), GSE25066, and a study by Yau et al. For the current study, we defined the adipocyte, which is calculated by utilizing a computational algorithm, xCell, as “intratumoral adipocyte”. These intratumoral adipocytes appropriately reflected mature adipocytes in a bulk tumor. The amount of intratumoral adipocytes demonstrated no relationship with survival. Intratumoral adipocyte-high tumors significantly enriched for metastasis and inflammation-related gene sets and are associated with a favorable tumor immune microenvironment, especially in the ER+/HER2- subtype. On the other hand, intratumoral adipocyte-low tumors significantly enriched for cell cycle and cell proliferation-related gene sets. Correspondingly, intratumoral adipocyte-low tumors are associated with advanced pathological grades and inversely correlated with MKI67 expression. In conclusion, a high amount of intratumoral adipocytes in breast cancer was associated with inflammation, metastatic pathways, cancer stemness, and favorable tumor immune microenvironment. However, a low amount of adipocytes was associated with a highly proliferative tumor in ER-positive breast cancer. This cancer biology may explain the reason why patient survival did not differ by the amount of adipocytes.

scholarly journals Exosomal miRNA: Small Molecules, Big Impact in Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Valentin Vautrot ◽  
Gaëtan Chanteloup ◽  
Mohammed Elmallah ◽  
Marine Cordonnier ◽  
François Aubin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Biology ◽  
Noncoding Rna ◽  
Cell Types ◽  
Response To Therapy ◽  
Bioactive Molecules ◽  
Premetastatic Niche ◽  
Rna Molecules ◽  
Small Noncoding Rna ◽  
Exosomal Mirna

Colorectal cancer (CRC) is one of the major causes of cancer-related deaths worldwide. Tumor microenvironment (TME) contains many cell types including stromal cells, immune cells, and endothelial cells. The TME modulation explains the heterogeneity of response to therapy observed in patients. In this context, exosomes are emerging as major contributors in cancer biology. Indeed, exosomes are implicated in tumor proliferation, angiogenesis, invasion, and premetastatic niche formation. They contain bioactive molecules such as proteins, lipids, and RNAs. More recently, many studies on exosomes have focused on miRNAs, small noncoding RNA molecules able to influence protein expression. In this review, we describe miRNAs transported by exosomes in the context of CRC and discuss their influence on TME and their potential as circulating biomarkers. This overview underlines emerging roles for exosomal miRNAs in cancer research for the near future.

scholarly journals Identifying metastasis-initiating miRNA-target regulations of colorectal cancer from expressional changes in primary tumors

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jongmin Lee ◽  
Hye Kyung Hong ◽  
Sheng-Bin Peng ◽  
Tae Won Kim ◽  
Woo Yong Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Mirna Target ◽  
Target Genes ◽  
Expression Profiles ◽  
Statistical Significance ◽  
Primary Tumors ◽  
Significant Difference

Abstract Colorectal cancer (CRC) is prevalent with high mortality, with liver metastasis contributing as a major factor that worsens the survival of patients. The roles of miRNAs in CRC have been elucidated, subsequent to recent studies that suggest the involvement of miRNAs in cancer biology. In this study, we compare the miRNA and gene expression profiles of primary tumors between two groups of patients (with and without liver metastasis) to identify the metastasis-initiating microRNA-target gene regulations. Analysis from 33 patients with metastasis and 14 patients without metastasis revealed that 17 miRNAs and their 198 predicted target genes are differentially expressed, where the target genes showed association with cancer progression and metastasis with statistical significance. In order to evaluate the clinical implications of the findings, we classified CRC patients of independent data into two groups based on the identified miRNA-target regulations, where one group was closer to primary tumors with metastasis than the other group. The comparison of survival showed statistically significant difference, thereby implying the roles of the identified miRNA-target regulations in cancer progression and metastasis. The identification of metastasis-initiating miRNA-target regulations in this study will lead to better understanding of the roles of miRNAs in CRC progression.

Single-Cell Epigenomics Reveals Mechanisms of Cancer Progression

2022 ◽  
Vol 6 (1) ◽  
Author(s):  
Lindsay M. LaFave ◽  
Rachel Savage ◽  
Jason D. Buenrostro
Keyword(s):  
Single Cell ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Annual Review ◽  
Publication Date ◽  
Cancer Evolution ◽  
Regulatory State ◽  
Cellular Functions ◽  
Cancer Initiation ◽  
Gene Regulatory

Cancer initiation is driven by the cooperation between genetic and epigenetic aberrations that disrupt gene regulatory programs critical to maintain specialized cellular functions. After initiation, cells acquire additional genetic and epigenetic alterations influenced by tumor-intrinsic and -extrinsic mechanisms, which increase intratumoral heterogeneity, reshape the cell's underlying gene regulatory network, and promote cancer evolution. Furthermore, environmental or therapeutic insults drive the selection of heterogeneous cell states, with implications for cancer initiation, maintenance, and drug resistance. The advancement of single-cell genomics has begun to uncover the full repertoire of chromatin and gene expression states (cell states) that exist within individual tumors. These single-cell analyses suggest that cells diversify in their regulatory states upon transformation by co-opting damage-induced and nonlineage regulatory programs that can lead to epigenomic plasticity. Here, we review these recent studies related to regulatory state changes in cancer progression and highlight the growing single-cell epigenomics toolkit poised to address unresolved questions in the field. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Genetic and Epigenetic Events Generate Multiple Pathways in Colorectal Cancer Progression

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Massimo Pancione ◽  
Andrea Remo ◽  
Vittorio Colantuoni
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Current Knowledge ◽  
Alternative Pathway ◽  
Epigenetic Events ◽  
Cells Of Origin ◽  
Common Causes ◽  
Colorectal Cancer Progression

Colorectal cancer (CRC) is one of the most common causes of death, despite decades of research. Initially considered as a disease due to genetic mutations, it is now viewed as a complex malignancy because of the involvement of epigenetic abnormalities. A functional equivalence between genetic and epigenetic mechanisms has been suggested in CRC initiation and progression. A hallmark of CRC is its pathogenetic heterogeneity attained through at least three distinct pathways: a traditional (adenoma-carcinoma sequence), an alternative, and more recently the so-called serrated pathway. While the alternative pathway is more heterogeneous and less characterized, the traditional and serrated pathways appear to be more homogeneous and clearly distinct. One unsolved question in colon cancer biology concerns the cells of origin and from which crypt compartment the different pathways originate. Based on molecular and pathological evidences, we propose that the traditional and serrated pathways originate from different crypt compartments explaining their genetic/epigenetic and clinicopathological differences. In this paper, we will discuss the current knowledge of CRC pathogenesis and, specifically, summarize the role of genetic/epigenetic changes in the origin and progression of the multiple CRC pathways. Elucidation of the link between the molecular and clinico-pathological aspects of CRC would improve our understanding of its etiology and impact both prevention and treatment.

scholarly journals Signaling of Tumor-Derived sEV Impacts Melanoma Progression

2020 ◽  
Vol 21 (14) ◽  
pp. 5066 ◽  
Author(s):  
Aneta Zebrowska ◽  
Piotr Widlak ◽  
Theresa Whiteside ◽  
Monika Pietrowska
Keyword(s):  
Cancer Progression ◽  
Cancer Biology ◽  
Melanoma Cells ◽  
Response To Therapy ◽  
Host Immune System ◽  
Development Activity ◽  
Tumor Biopsy ◽  
Potential Biomarkers

Small extracellular vesicles (sEV or exosomes) are nanovesicles (30–150 nm) released both in vivo and in vitro by most cell types. Tumor cells produce sEV called TEX and disperse them throughout all body fluids. TEX contain a cargo of proteins, lipids, and RNA that is similar but not identical to that of the “parent” producer cell (i.e., the cargo of exosomes released by melanoma cells is similar but not identical to exosomes released by melanocytes), possibly due to selective endosomal packaging. TEX and their role in cancer biology have been intensively investigated largely due to the possibility that TEX might serve as key component of a “liquid tumor biopsy.” TEX are also involved in the crosstalk between cancer and immune cells and play a key role in the suppression of anti-tumor immune responses, thus contributing to the tumor progression. Most of the available information about the TEX molecular composition and functions has been gained using sEV isolated from supernatants of cancer cell lines. However, newer data linking plasma levels of TEX with cancer progression have focused attention on TEX in the patients’ peripheral circulation as potential biomarkers of cancer diagnosis, development, activity, and response to therapy. Here, we consider the molecular cargo and functions of TEX as potential biomarkers of one of the most fatal malignancies—melanoma. Studies of TEX in plasma of patients with melanoma offer the possibility of an in-depth understanding of the melanoma biology and response to immune therapies. This review features melanoma cell-derived exosomes (MTEX) with special emphasis on exosome-mediated signaling between melanoma cells and the host immune system.

Epigenetic regulation and promising therapies in colorectal cancer

2021 ◽  
Vol 14 ◽  
Author(s):  
Chandra Kishore
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Cancer Colorectal ◽  
Review Paper ◽  
Genetic Changes ◽  
Proline Isomerization ◽  
Cancer Initiation ◽  
Recent Developments ◽  
Dna Strand

: The recent developments in epigenetics have shown a very important role of epigenetic changes in cancer initiation, development, and progression. Some of the important histone modifications shown to occur are methylation, acetylation, phosphorylation, citrullination, sumoylation, ADP ribosylation, deamination, ubiquitination, formylation, O-GlcNAcylation, propionylation, butyrylation, proline isomerization, and crotonylation but most of the studies in past had limited their studies mainly on histone methylation, acetylation, and phosphorylation. Modification of DNA strand by hypermethylation and hypomethylation regulates genomic instability and promotes cancer. Colorectal cancer involves multiple changes in epigenetic marks present on histone residues and DNA, which in collaboration with genetic changes, drives cancer progression. In this review paper, basic concepts of epigenetics relevant to cancer development are discussed followed by its significance in understanding the mechanism of colon carcinogenesis. Some of the epigenetic target based drugs are also discussed in the relevant sections to give an idea of the potential promises of epigenetics for colorectal cancer treatment.

scholarly journals Patient-derived tumor models: a more suitable tool for pre-clinical studies in colorectal cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Giulia Rizzo ◽  
Andrea Bertotti ◽  
Simonetta Maria Leto ◽  
Stefania Vetrano
Keyword(s):  
Colorectal Cancer ◽  
Cancer Biology ◽  
Response To Therapy ◽  
Cellular Interactions ◽  
Immunodeficient Mice ◽  
Screening And Surveillance ◽  
Clinical Models ◽  
Clinical Tools ◽  
Screening Platform ◽  
Novel Therapeutic Strategies

AbstractColorectal cancer (CRC), despite the advances in screening and surveillance, remains the second most common cause of cancer death worldwide. The biological inadequacy of pre-clinical models to fully recapitulate the multifactorial etiology and the complexity of tumor microenvironment and human CRC’s genetic heterogeneity has limited cancer treatment development. This has led to the development of Patient-derived models able to phenocopy as much as possible the original inter- and intra-tumor heterogeneity of CRC, reflecting the tumor microenvironment’s cellular interactions. Implantation of patient tissue into immunodeficient mice hosts and the culture of tumor organoids have allowed advances in cancer biology and metastasis. This review highlights the advantages and limits of Patient-derived models as innovative and valuable pre-clinical tools to study progression and metastasis of CRC, develop novel therapeutic strategies by creating a drug screening platform, and predict the efficacy of clinical response to therapy.

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