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Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 78054

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Dr. Carmine Stolfi

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Guest Editor

Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Interests: colorectal cancer; immunotherapy; inflammatory bowel diseases; anti-cancer drugs
Special Issues, Collections and Topics in MDPI journals

Dr. Federica Laudisi

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Guest Editor

Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Interests: colorectal carcinogenesis; STAT3 signaling; drug repositioning; inflammatory bowel diseases; gut homeostasis; intestinal microbiota; mucosal immunology; inflammasome
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Many epidemiologic and molecular studies showed that chronic inflammation is an independent risk factor for the development of gastrointestinal cancers (e.g., chronic gastritis for gastric cancer, chronic hepatitis for liver cancer, inflammatory bowel diseases for colorectal cancer). Moreover, the infiltration of immune/inflammatory cells is known to occur in all the stages of gastrointestinal carcinogenesis and to play a major role in such a process. Although inﬂammatory cell-derived cytokines/factors can either directly or indirectly promote cancer cell growth and invasion, under speciﬁc inﬂammatory conditions, immune cells can mediate antitumor responses with the downstream effect of eliminating dysplastic and cancerous cells. The specific nature of the inflammatory response and the tissue context may thus determine the beneficial versus the detrimental effects of inflammation in both tumor initiation and progression.

Despite recent scientific advances, the molecular and cellular pathways connecting inflammation and cancer are still being uncovered. A better understanding of this liaison may definitely improve our knowledge about cancer cell biology and offer opportunities for the design of new therapeutic interventions.

In this Special Issue, we invite investigators working on inflammation and gastrointestinal cancers to submit original papers or reviews to shed further light on this complex field. Potential topics include but are not limited to:

- Mechanistic studies on esophageal, liver, pancreatic, gastric, and colorectal carcinogenesis;

- Role of epigenetic alterations in gastrointestinal cancers;

- Effects of dietary and/or lifestyle changes on gastrointestinal inflammation and tumorigenesis;

- Effects of the microbiota on inflammation, carcinogenesis, and cancer therapy;

- Role of inflammatory cell-derived factors on cancer immunosurveillance and immunoediting;

- Therapeutic strategies and novel clinical approaches for gastrointestinal cancers (e.g., chemotherapeutics, immunotherapy, natural compounds, drug repositioning, precision medicine);

- Prognostic and predictive biomarkers reflecting qualitative and quantitative disease activity, progression of cancer, and prediction of the outcome of the treatment.

Dr. Carmine Stolfi
Dr. Federica Laudisi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

colorectal cancer
gastric cancer
liver cancer
inflammatory bowel diseases
tumor microenvironment
mucosal immunology
inflammasome
cytokines
microbiota
diet and lifestyle
epigenetic
drug repositioning
natural compounds
checkpoint inhibitors
prognostic biomarkers
immunotherapy
autophagy

Published Papers (12 papers)

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Research

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20 pages, 3415 KiB

Open AccessArticle

Use of STAT6 Phosphorylation Inhibitor and Trimethylglycine as New Adjuvant Therapies for 5-Fluorouracil in Colitis-Associated Tumorigenesis

by Mónica G. Mendoza-Rodríguez, C. Ángel Sánchez-Barrera, Blanca E. Callejas, Verónica García-Castillo, Diana L. Beristain-Terrazas, Norma L. Delgado-Buenrostro, Yolanda I. Chirino, Sonia A. León-Cabrera, Miriam Rodríguez-Sosa, Emma Bertha Gutierrez-Cirlos, Carlos Pérez-Plasencia, Felipe Vaca-Paniagua, Marco Antonio Meraz-Ríos and Luis I. Terrazas

Int. J. Mol. Sci. 2020, 21(6), 2130; https://doi.org/10.3390/ijms21062130 - 20 Mar 2020

Cited by 22 | Viewed by 3470

Abstract

Colorectal cancer (CRC) is one of the most widespread and deadly types of neoplasia around the world, where the inflammatory microenvironment has critical importance in the process of tumor growth, metastasis, and drug resistance. Despite its limited effectiveness, 5-fluorouracil (5-FU) is the main drug utilized for CRC treatment. The combination of 5-FU with other agents modestly increases its effectiveness in patients. Here, we evaluated the anti-inflammatory Trimethylglycine and the Signal transducer and activator of transcription (STAT6) inhibitor AS1517499, as possible adjuvants to 5-FU in already established cancers, using a model of colitis-associated colon cancer (CAC). We found that these adjuvant therapies induced a remarkable reduction of tumor growth when administrated together with 5-FU, correlating with a reduction in STAT6-phosphorylation. This reduction upgraded the effect of 5-FU by increasing both levels of apoptosis and markers of cell adhesion such as E-cadherin, whereas decreased epithelial–mesenchymal transition markers were associated with aggressive phenotypes and drug resistance, such as β-catenin nuclear translocation and Zinc finger protein SNAI1 (SNAI1). Additionally, Il-10, Tgf-β, and Il-17a, critical pro-tumorigenic cytokines, were downmodulated in the colon by these adjuvant therapies. In vitro assays on human colon cancer cells showed that Trimethylglycine also reduced STAT6-phosphorylation. Our study is relatively unique in focusing on the effects of the combined administration of AS1517499 and Trimethylglycine together with 5-FU on already established CAC which synergizes to markedly reduce the colon tumor load. Together, these data point to STAT6 as a valuable target for adjuvant therapy in colon cancer. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

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Review

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24 pages, 4379 KiB

Open AccessReview

The Regulation of Intestinal Inflammation and Cancer Development by Type 2 Immune Responses

by Reyes Gamez-Belmonte, Lena Erkert, Stefan Wirtz and Christoph Becker

Int. J. Mol. Sci. 2020, 21(24), 9772; https://doi.org/10.3390/ijms21249772 - 21 Dec 2020

Cited by 10 | Viewed by 4450

Abstract

The gut is among the most complex organs of the human body. It has to exert several functions including food and water absorption while setting up an efficient barrier to the outside world. Dysfunction of the gut can be life-threatening. Diseases of the gastrointestinal tract such as inflammatory bowel disease, infections, or colorectal cancer, therefore, pose substantial challenges to clinical care. The intestinal epithelium plays an important role in intestinal disease development. It not only establishes an important barrier against the gut lumen but also constantly signals information about the gut lumen and its composition to immune cells in the bowel wall. Such signaling across the epithelial barrier also occurs in the other direction. Intestinal epithelial cells respond to cytokines and other mediators of immune cells in the lamina propria and shape the microbial community within the gut by producing various antimicrobial peptides. Thus, the epithelium can be considered as an interpreter between the microbiota and the mucosal immune system, safeguarding and moderating communication to the benefit of the host. Type 2 immune responses play important roles in immune-epithelial communication. They contribute to gut tissue homeostasis and protect the host against infections with helminths. However, they are also involved in pathogenic pathways in inflammatory bowel disease and colorectal cancer. The current review provides an overview of current concepts regarding type 2 immune responses in intestinal physiology and pathophysiology. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

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29 pages, 4010 KiB

Open AccessReview

The Macrophages-Microbiota Interplay in Colorectal Cancer (CRC)-Related Inflammation: Prognostic and Therapeutic Significance

by Silvia Mola, Chiara Pandolfo, Antonio Sica and Chiara Porta

Int. J. Mol. Sci. 2020, 21(18), 6866; https://doi.org/10.3390/ijms21186866 - 18 Sep 2020

Cited by 21 | Viewed by 5360

Abstract

Tumor-associated macrophages (TAMs) are the main population of myeloid cells infiltrating solid tumors and the pivotal orchestrators of cancer-promoting inflammation. However, due to their exceptional plasticity, macrophages can be also key effector cells and powerful activators of adaptive anti-tumor immunity. This functional heterogeneity is emerging in human tumors, colorectal cancer (CRC) in particular, where the dynamic co-existence of different macrophage subtypes influences tumor development, outcome, and response to therapies. Intestinal macrophages are in close interaction with enteric microbiota, which contributes to carcinogenesis and affects treatment outcomes. This interplay may be particularly relevant in CRC, one of the most prevalent and lethal cancer types in the world. Therefore, both macrophages and intestinal microbiota are considered promising prognostic indicators and valuable targets for new therapeutic approaches. Here, we discuss the current understanding of the molecular circuits underlying the interplay between macrophages and microbiota in CRC development, progression, and response to both conventional therapies and immunotherapies. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

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19 pages, 1646 KiB

Open AccessReview

Tumor Infiltrating Regulatory T Cells in Sporadic and Colitis-Associated Colorectal Cancer: The Red Little Riding Hood and the Wolf

by Massimo Claudio Fantini, Agnese Favale, Sara Onali and Federica Facciotti

Int. J. Mol. Sci. 2020, 21(18), 6744; https://doi.org/10.3390/ijms21186744 - 14 Sep 2020

Cited by 16 | Viewed by 3581

Abstract

Regulatory T cells represent a class of specialized T lymphocytes that suppress unwanted immune responses and size the activation of the immune system whereby limiting collateral damages in tissues involved by inflammation. In cancer, the accumulation of Tregs is generally associated with poor prognosis. Many lines of evidence indicate that Tregs accumulation in the tumor microenvironment (TME) suppresses the immune response against tumor-associated antigens (TAA), thus promoting tumor progression in non-small cell lung carcinoma (NSLC), breast carcinoma and melanoma. In colorectal cancer (CRC) the effect of Tregs accumulation is debated. Some reports describe the association of high number of Tregs in CRC stroma with a better prognosis while others failed to find any association. These discordant results stem from the heterogeneity of the immune environment generated in CRC in which anticancer immune response may coexists with tumor promoting inflammation. Moreover, different subsets of Tregs have been identified that may exert different effects on cancer progression depending on tumor stage and their location within the tumor mass. Finally, Tregs phenotypic plasticity may be induced by cytokines released in the TME by dysplastic and other tumor-infiltrating cells thus affecting their functional role in the tumor. Here, we reviewed the recent literature about the role of Tregs in CRC and in colitis-associated colorectal cancer (CAC), where inflammation is the main driver of tumor initiation and progression. We tried to explain when and how Tregs can be considered to be the “good” or the “bad” in the colon carcinogenesis process on the basis of the available data concluding that the final effect of Tregs on sporadic CRC and CAC depends on their localization within the tumor, the subtype of Tregs involved and their phenotypic plasticity. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

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30 pages, 3684 KiB

Open AccessReview

mRNA Post-Transcriptional Regulation by AU-Rich Element-Binding Proteins in Liver Inflammation and Cancer

by Dobrochna Dolicka, Cyril Sobolewski, Marta Correia de Sousa, Monika Gjorgjieva and Michelangelo Foti

Int. J. Mol. Sci. 2020, 21(18), 6648; https://doi.org/10.3390/ijms21186648 - 11 Sep 2020

Cited by 21 | Viewed by 4984

Abstract

AU-rich element-binding proteins (AUBPs) represent important post-transcriptional regulators of gene expression. AUBPs can bind to the AU-rich elements present in the 3’-UTR of more than 8% of all mRNAs and are thereby able to control the stability and/or translation of numerous target mRNAs. The regulation of the stability and the translation of mRNA transcripts by AUBPs are highly complex processes that occur through multiple mechanisms depending on the cell type and the cellular context. While AUBPs have been shown to be involved in inflammatory processes and the development of various cancers, their important role and function in the development of chronic metabolic and inflammatory fatty liver diseases (FLDs), as well as in the progression of these disorders toward cancers such as hepatocellular carcinoma (HCC), has recently started to emerge. Alterations of either the expression or activity of AUBPs are indeed significantly associated with FLDs and HCC, and accumulating evidence indicates that several AUBPs are deeply involved in a significant number of cellular processes governing hepatic metabolic disorders, inflammation, fibrosis, and carcinogenesis. Herein, we discuss our current knowledge of the roles and functions of AUBPs in liver diseases and cancer. The relevance of AUBPs as potential biomarkers for different stages of FLD and HCC, or as therapeutic targets for these diseases, are also highlighted. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

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20 pages, 739 KiB

Open AccessReview

Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes

by Federica Perillo, Chiara Amoroso, Francesco Strati, Maria Rita Giuffrè, Angélica Díaz-Basabe, Georgia Lattanzi and Federica Facciotti

Int. J. Mol. Sci. 2020, 21(15), 5389; https://doi.org/10.3390/ijms21155389 - 29 Jul 2020

Cited by 35 | Viewed by 8398

Abstract

Colorectal cancer (CRC) is a multifaceted disease influenced by both environmental and genetic factors. A large body of literature has demonstrated the role of gut microbes in promoting inflammatory responses, creating a suitable microenvironment for the development of skewed interactions between the host and the gut microbiota and cancer initiation. Even if surgery is the primary therapeutic strategy, patients with advanced disease or cancer recurrence after surgery remain difficult to cure. Therefore, the gut microbiota has been proposed as a novel therapeutic target in light of recent promising data in which it seems to modulate the response to cancer immunotherapy. The use of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics, and fecal microbiota transplantation, is therefore considered to support current therapies in CRC management. In this review, we will discuss the importance of host−microbe interactions in CRC and how promoting homeostatic immune responses through microbe-targeted therapies may be useful in preventing/treating CRC development. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

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17 pages, 4356 KiB

Open AccessReview

The Adenosine System at the Crossroads of Intestinal Inflammation and Neoplasia

by Vanessa D’Antongiovanni, Matteo Fornai, Carolina Pellegrini, Laura Benvenuti, Corrado Blandizzi and Luca Antonioli

Int. J. Mol. Sci. 2020, 21(14), 5089; https://doi.org/10.3390/ijms21145089 - 18 Jul 2020

Cited by 18 | Viewed by 4242

Abstract

Adenosine is a purine nucleoside, resulting from the degradation of adenosine triphosphate (ATP). Under adverse conditions, including hypoxia, ischemia, inflammation, or cancer, the extracellular levels of adenosine increase significantly. Once released, adenosine activates cellular signaling pathways through the engagement of the four known G-protein-coupled receptors, adenosine A₁ receptor subtype (A₁), A_2A, A_2B, and A₃. These receptors, expressed virtually on all immune cells, mitigate all aspects of immune/inflammatory responses. These immunosuppressive effects contribute to blunt the exuberant inflammatory responses, shielding cells, and tissues from an excessive immune response and immune-mediated damage. However, a prolonged persistence of increased adenosine concentrations can be deleterious, participating in the creation of an immunosuppressed niche, ideal for neoplasia onset and development. Based on this evidence, the present review has been conceived to provide a comprehensive and critical overview of the involvement of adenosine system in shaping the molecular mechanisms underlying the enteric chronic inflammation and in promoting the generation of an immunosuppressive niche useful for the colorectal tumorigenesis. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

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19 pages, 802 KiB

Open AccessReview

Repositioning of Anthelmintic Drugs for the Treatment of Cancers of the Digestive System

by Federica Laudisi, Martin Marônek, Antonio Di Grazia, Giovanni Monteleone and Carmine Stolfi

Int. J. Mol. Sci. 2020, 21(14), 4957; https://doi.org/10.3390/ijms21144957 - 13 Jul 2020

Cited by 33 | Viewed by 15136

Abstract

Tumors of the digestive system, when combined together, account for more new cases and deaths per year than tumors arising in any other system of the body and their incidence continues to increase. Despite major efforts aimed at discovering and validating novel and effective drugs against these malignancies, the process of developing such drugs remains lengthy and costly, with high attrition rates. Drug repositioning (also known as drug repurposing), that is, the process of finding new uses for approved drugs, has been gaining popularity in oncological drug development as it provides the opportunity to expedite promising anti-cancer agents into clinical trials. Among the drugs considered for repurposing in oncology, compounds belonging to some classes of anthelmintics—a group of agents acting against infections caused by parasitic worms (helminths) that colonize the mammalian intestine—have shown pronounced anti-tumor activities and attracted particular attention due to their ability to target key oncogenic signal transduction pathways. In this review, we summarize and discuss the available experimental and clinical evidence about the use of anthelmintic drugs for the treatment of cancers of the digestive system. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

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31 pages, 5819 KiB

Open AccessReview

Intestinal Macrophages at the Crossroad between Diet, Inflammation, and Cancer

by Greta Caprara, Paola Allavena and Marco Erreni

Int. J. Mol. Sci. 2020, 21(14), 4825; https://doi.org/10.3390/ijms21144825 - 08 Jul 2020

Cited by 26 | Viewed by 5958

Abstract

Intestinal macrophages are key players in the regulation of the oral tolerance, controlling gut homeostasis by discriminating innocuous antigens from harmful pathogens. Diet exerts a significant impact on human health, influencing the composition of gut microbiota and the developing of several non-communicable diseases, including cancer. Nutrients and microbiota are able to modify the profile of intestinal macrophages, shaping their key function in the maintenance of the gut homeostasis. Intestinal disease often occurs as a breakdown of this balance: defects in monocyte–macrophage differentiation, wrong dietary habits, alteration of microbiota composition, and impairment in the resolution of inflammation may contribute to the development of intestinal chronic inflammation and colorectal cancer. Accordingly, dietary interventions and macrophage-targeted therapies are emerging as innovative tools for the treatment of several intestinal pathologies. In this review, we will describe the delicate balance between diet, microbiota and intestinal macrophages in homeostasis and how the perturbation of this equilibrium may lead to the occurrence of inflammatory conditions in the gut. The understanding of the molecular pathways and dietary factors regulating the activity of intestinal macrophages might result in the identification of innovative targets for the treatments of intestinal pathologies. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

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14 pages, 240 KiB

Open AccessReview

Association Between Celiac Disease and Cancer

by Irene Marafini, Giovanni Monteleone and Carmine Stolfi

Int. J. Mol. Sci. 2020, 21(11), 4155; https://doi.org/10.3390/ijms21114155 - 10 Jun 2020

Cited by 29 | Viewed by 5760

Abstract

Celiac disease (CD) is a chronic enteropathy that develops in genetically susceptible individuals after the ingestion of gluten. There has been a substantial increase in CD prevalence in the last 50 years, and it is now estimated that this disease affects approximately 1% of the population in the Western world. In the large majority of cases, CD is a benign disease, characterized by the complete resolution of symptoms and a normal life expectancy after the onset of a gluten-free diet (GFD). However, failure to adhere to a strict GFD bears the risk of adverse events and increases mortality. A considerable number of studies have considered the possible association between CD and neoplasms. In particular, an increased risk of malignancies, such as cancers of the gastrointestinal tract and intestinal lymphomas, has been reported. In this review, we summarize and discuss the current evidence on the possible association between CD and cancer. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

19 pages, 1310 KiB

Open AccessReview

New Insights into Molecular Links Between Microbiota and Gastrointestinal Cancers: A Literature Review

by Yash Raj Rastogi, Adesh K. Saini, Vijay Kumar Thakur and Reena V. Saini

Int. J. Mol. Sci. 2020, 21(9), 3212; https://doi.org/10.3390/ijms21093212 - 01 May 2020

Cited by 24 | Viewed by 4368

Abstract

Despite decades of exhaustive research on cancer, questions about cancer initiation, development, recurrence, and metastasis have still not been completely answered. One of the reasons is the plethora of factors acting simultaneously in a tumour microenvironment, of which not all have garnered attention. One such factor that has long remained understudied and has only recently received due attention is the host microbiota. Our sheer-sized microbiota exists in a state of symbiosis with the body and exerts significant impact on our body’s physiology, ranging from immune-system development and regulation to neurological and cognitive development. The presence of our microbiota is integral to our development, but a change in its composition (microbiota dysbiosis) can often lead to adverse effects, increasing the propensity of serious diseases like cancers. In the present review, we discuss environmental and genetic factors that cause changes in microbiota composition, disposing of the host towards cancer, and the molecular mechanisms (such as β-catenin signalling) and biochemical pathways (like the generation of oncogenic metabolites like N-nitrosamines and hydrogen sulphide) that the microbiota uses to initiate or accelerate cancers, with emphasis on gastrointestinal cancers. Moreover, we discuss how microbiota can adversely influence the success of colorectal-cancer chemotherapy, and its role in tumour metastasis. We also attempted to resolve conflicting results obtained for the butyrate effect on tumour suppression in the colon, often referred to as the ‘butyrate paradox’. In addition, we suggest the development of microbiota-based biomarkers for early cancer diagnosis, and a few target molecules of which the inhibition can increase the overall chances of cancer cure. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

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15 pages, 1113 KiB

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Iron Metabolism in Cancer Progression

by Stefania Forciniti, Luana Greco, Fabio Grizzi, Alberto Malesci and Luigi Laghi

Int. J. Mol. Sci. 2020, 21(6), 2257; https://doi.org/10.3390/ijms21062257 - 24 Mar 2020

Cited by 58 | Viewed by 11480

Abstract

Iron is indispensable for cell metabolism of both normal and cancer cells. In the latter, several disruptions of its metabolism occur at the steps of tumor initiation, progression and metastasis. Noticeably, cancer cells require a large amount of iron, and exhibit a strong dependence on it for their proliferation. Numerous iron metabolism-related proteins and signaling pathways are altered by iron in malignancies, displaying the pivotal role of iron in cancer. Iron homeostasis is regulated at several levels, from absorption by enterocytes to recycling by macrophages and storage in hepatocytes. Mutations in HFE gene alter iron homeostasis leading to hereditary hemochromatosis and to an increased cancer risk because the accumulation of iron induces oxidative DNA damage and free radical activity. Additionally, the iron capability to modulate immune responses is pivotal in cancer progression. Macrophages show an iron release phenotype and potentially deliver iron to cancer cells, resulting in tumor promotion. Overall, alterations in iron metabolism are among the metabolic and immunological hallmarks of cancer, and further studies are required to dissect how perturbations of this element relate to tumor development and progression. Full article

(This article belongs to the Special Issue Inflammation and Gastrointestinal Cancers: Molecular Mechanisms and Therapies 1.0)

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