The role of dietary polyphenols in the moderation of the inflammatory response in early stage colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of cancer-related death. It is the second most frequently diagnosed malignancy in Europe and third worldwide. Colorectal malignancies diagnosed at an early stage offer a promising survival rate. However, advanced tumors often present distant metastases even after the complete resection of a primary tumor. Therefore, novel biomarkers of CRC are sorely needed in the diagnosis and prognosis of this common malignancy. A family of chemokines are composed of small, secreted proteins. They are best known for their ability to stimulate the migration of several cell types. Some investigations have indicated that chemokines are involved in cancer development, including CRC. This article presents current knowledge regarding chemokines and their specific receptors in CRC progression. Moreover, the prime aim of this review is to summarize the potential role of these proteins as biomarkers in the diagnosis and prognosis of CRC.

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Probiotics in colorectal cancer (CRC) with emphasis on mechanisms of action and current perspectives

Journal of Medical Microbiology ◽

10.1099/jmm.0.048975-0 ◽

2013 ◽

Vol 62 (8) ◽

pp. 1107-1123 ◽

Cited By ~ 58

Author(s):

Imen Kahouli ◽

Catherine Tomaro-Duchesneau ◽

Satya Prakash

Keyword(s):

Colorectal Cancer ◽

Early Stage ◽

Tumour Progression ◽

Great Promise ◽

Anticancer Compounds ◽

Beneficial Effects ◽

Physico Chemical ◽

Recent Developments ◽

Chemical Conditions

Colorectal cancer (CRC) is the third most common form of cancer. Diverse therapies such as chemotherapy, immunotherapy and radiation have shown beneficial effects, but are limited because of their safety and toxicity. Probiotic formulations have shown great promise in CRC as preventive and early stage therapeutics. This review highlights the importance of a balanced intestinal microbiota and summarizes the recent developments in probiotics for treating CRC. Specifically, this report describes evidence of the role of probiotics in modulating the microbiota, in improving the physico-chemical conditions of the gut and in reducing oxidative stress. It also discusses the mechanisms of probiotics in inhibiting tumour progression, in producing anticancer compounds and in modulating the host immune response. Even though some of these effects were observed in several clinical trials, when probiotic formulations were used as a supplement to CRC therapies, the application of probiotics as biotherapeutics against CRC still needs further investigation.

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Role of body composition in early stage colorectal cancer (CRC) outcomes

Annals of Oncology ◽

10.1093/annonc/mdx393.016 ◽

2017 ◽

Vol 28 ◽

pp. v165

Author(s):

J. Hopkins ◽

D. Bigam ◽

D. Eurich ◽

V. Baracos ◽

M. Sawyer

Keyword(s):

Colorectal Cancer ◽

Body Composition ◽

Early Stage

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The role of the in situ local inflammatory response in predicting recurrence and survival in patients with primary operable colorectal cancer

Cancer Treatment Reviews ◽

10.1016/j.ctrv.2011.09.001 ◽

2012 ◽

Vol 38 (5) ◽

pp. 451-466 ◽

Cited By ~ 92

Author(s):

C.S.D. Roxburgh ◽

D.C. McMillan

Keyword(s):

Colorectal Cancer ◽

Inflammatory Response ◽

Local Inflammatory Response

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THE ROLE OF MARKERS OF SYSTEMIC INFLAMMATORY RESPONSE IN THE POSTOPERATIVE PERIOD. REVIEW

Surgical Practice ◽

10.38181/2223-2427-2021-1-30-38 ◽

2021 ◽

pp. 30-38

Author(s):

V. A. Kubyshkin ◽

L. M. Samokhodskaya ◽

Yu. M. Korolev

Keyword(s):

Inflammatory Response ◽

Clinical Symptoms ◽

Early Stage ◽

Complete Information ◽

Infectious Complications ◽

Diagnostic Measures ◽

Reactive Protein ◽

Markers Of Inflammation ◽

The Moment

Despite all the achievements of modern surgery, the number of postoperative infectious complications in the world remains high. Their occurrence leads to a longer period of patients’ hospitalization, requires the use of additional medical and diagnostic measures, which ultimately leads to higher treatment costs and significant financial losses in the health care system. Therefore, it is important to identify postoperative complications at an early stage, even before the development of pronounced clinical symptoms, and to predict their possible development in a certain category of patients. For these purposes, scientists try to use various laboratory markers. In this paper, we analyzed both well-known indicators of the inflammatory response, such as: C-reactive protein, albumin, their ratio, procalcitonin and interleukin-6, and relatively new parameters that research teams are trying to apply for these purposes: neutrophil granularity intensity and neutrophil reactivity intensity, pancreatic stone protein and pancreatitis-associated protein. We tried to collect the most complete information available at the moment, evaluate the opinions of researchers, identify contradictions in their works and try to explain their cause. As a result, it turned out that even the markers of inflammation known for many years are not absolutely specific for postoperative infectious complications. We concluded that most of the laboratory parameters described in this article can be used to some extent in the early diagnosis of postoperative infectious complications, but if we want to obtain more complete information in this area of knowledge, it is necessary to conduct new largescale studies.

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Inactivation of Interferon Regulatory Factor 1 Causes Susceptibility to Colitis-Associated Colorectal Cancer

Scientific Reports ◽

10.1038/s41598-019-55378-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Thiviya Jeyakumar ◽

Nassima Fodil ◽

Lauren Van Der Kraak ◽

Charles Meunier ◽

Romain Cayrol ◽

...

Keyword(s):

Colorectal Cancer ◽

Chronic Inflammation ◽

Cancer Susceptibility ◽

Early Stage ◽

Differential Susceptibility ◽

Lymphoid Cells ◽

Enterocyte Proliferation ◽

Interferon Regulatory Factor 1 ◽

And Function

AbstractThe mechanisms linking chronic inflammation of the gut (IBD) and increased colorectal cancer susceptibility are poorly understood. IBD risk is influenced by genetic factors, including the IBD5 locus (human 5q31), that harbors the IRF1 gene. A cause-to-effect relationship between chronic inflammation and colorectal cancer, and a possible role of IRF1 were studied in Irf1-/- mice in a model of colitis-associated colorectal cancer (CA-CRC) induced by azoxymethane and dextran sulfate. Loss of Irf1 causes hyper-susceptibility to CA-CRC, with early onset and increased number of tumors leading to rapid lethality. Transcript profiling (RNA-seq) and immunostaining of colons shows heightened inflammation and enhanced enterocyte proliferation in Irf1−/− mutants, prior to appearance of tumors. Considerable infiltration of leukocytes is seen in Irf1−/− colons at this early stage, and is composed primarily of proinflammatory Gr1+ Cd11b+ myeloid cells and other granulocytes, as well as CD4+ lymphoid cells. Differential susceptibility to CA-CRC of Irf1−/− vs. B6 controls is fully transferable through hematopoietic cells as observed in bone marrow chimera studies. Transcript signatures seen in Irf1−/− mice in response to AOM/DSS are enriched in clinical specimens from patients with IBD and with colorectal cancer. In addition, IRF1 expression in the colon is significantly decreased in late stage colorectal cancer (stages 3, 4) and is associated with poorer prognosis. This suggests that partial or complete loss of IRF1 expression alters the type, number, and function of immune cells in situ during chronic inflammation, possibly via the creation of a tumor-promoting environment.

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Stage I–IV Colorectal Cancer Prognosis Can Be Predicted by Type and Number of Intratumoral Macrophages and CLEVER-1+ Vessel Density

Cancers ◽

10.3390/cancers13235988 ◽

2021 ◽

Vol 13 (23) ◽

pp. 5988

Author(s):

Annika Ålgars ◽

Lotta Kemppinen ◽

Ruth Fair-Mäkelä ◽

Harri Mustonen ◽

Caj Haglund ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Early Stage ◽

Prognostic Significance ◽

Lymphatic Vessels ◽

Vessel Density ◽

Stage I ◽

Disease Stage ◽

Prognostic Role

Macrophages, which are key players in the tumor microenvironment and affect the prognosis of many cancers, interact with lymphatic vessels in tumor tissue. However, the prognostic role of tumor-associated macrophages (TAM) and lymphatic vessels in human colorectal cancer (CRC) remains controversial. We investigated the prognostic role of CD68+ and CLEVER-1+ (common lymphatic endothelial and vascular endothelial receptor 1) TAMs in addition to CLEVER-1+ lymphatic vessels in 498 stage I–IV CRC patients. The molecular markers were detected by immunohistochemical (IHC) analysis. The results showed that, in early stage I CRC and in young patients (age below median, ≤67.4 years), a high number of CD68+ and CLEVER-1+ TAMs was associated with longer disease-specific survival (DSS). In early stage I CRC, high intratumoral CLEVER-1+ lymphatic vessel density (LVD) predicted a favorable prognosis, whereas the opposite pattern was observed in stage II CRC. The highest density of CLEVER-1+ lymphatic vessels was found in metastatic disease. The combination of intratumoral CLEVER-1+ lymphatic vesselhigh + CD68+ TAMlow was associated with poor DSS in stage I–IV rectal cancer. The present results indicate that the prognostic significance of intratumoral macrophages and CLEVER-1+ lymphatic vessels differs according to disease stage, reflecting the dynamic changes occurring in the tumor microenvironment during disease progression.

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Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.744606 ◽

2021 ◽

Vol 11 ◽

Author(s):

Siti Maryam Ahmad Kendong ◽

Raja Affendi Raja Ali ◽

Khairul Najmi Muhammad Nawawi ◽

Hajar Fauzan Ahmad ◽

Norfilza Mohd Mokhtar

Keyword(s):

Colorectal Cancer ◽

Environmental Factors ◽

Gut Microbiota ◽

Early Onset ◽

Early Stage ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Gut Dysbiosis ◽

Early Onset Colorectal Cancer

Colorectal cancer (CRC) is a heterogeneous disease that commonly affects individuals aged more than 50 years old globally. Regular colorectal screening, which is recommended for individuals aged 50 and above, has decreased the number of cancer death toll over the years. However, CRC incidence has increased among younger population (below 50 years old). Environmental factors, such as smoking, dietary factor, urbanization, sedentary lifestyle, and obesity, may contribute to the rising trend of early-onset colorectal cancer (EOCRC) because of the lack of genetic susceptibility. Research has focused on the role of gut microbiota and its interaction with epithelial barrier genes in sporadic CRC. Population with increased consumption of grain and vegetables showed high abundance of Prevotella, which reduces the risk of CRC. Microbes, such as Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli deteriorate in the intestinal barrier, which leads to the infiltration of inflammatory mediators and chemokines. Gut dysbiosis may also occur following inflammation as clearly observed in animal model. Both gut dysbiosis pre- or post-inflammatory process may cause major alteration in the morphology and functional properties of the gut tissue and explain the pathological outcome of EOCRC. The precise mechanism of disease progression from an early stage until cancer establishment is not fully understood. We hypothesized that gut dysbiosis, which may be influenced by environmental factors, may induce changes in the genome, metabolome, and immunome that could destruct the intestinal barrier function. Also, the possible underlying inflammation may give impact microbial community leading to disruption of physical and functional role of intestinal barrier. This review explains the potential role of the interaction among host factors, gut microenvironment, and gut microbiota, which may provide an answer to EOCRC.

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Potential Role of Traditional Chinese Medicines by Wnt/β-Catenin Pathway Compared With Targeted Small Molecules in Colorectal Cancer Therapy

Frontiers in Pharmacology ◽

10.3389/fphar.2021.690501 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jinrong Chang ◽

Hoileong Wong Xavier ◽

Dongfeng Chen ◽

Yamei Liu ◽

Hui Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Potential Role ◽

Early Stage ◽

Precancerous Lesions ◽

Public Health Problem ◽

New Drugs ◽

Traditional Chinese Medicines ◽

Chinese Medicines ◽

Incidence And Mortality

Colorectal cancer (CRC) has become a global public health problem because of its high incidence and mortality rate worldwide. The previous clinical treatment for CRC mainly involves conventional surgery, chemotherapy, and radiotherapy. With the development of tumor molecular targeted therapy, small molecule inhibitors present a great advantage in improving the survival of patients with advanced CRC. However, various side effects and drug resistance induced by chemotherapy are still the major obstacles to improve the clinical benefit. Thus, it is crucial to find new and alternative drugs for CRC treatment. Traditional Chinese medicines (TCMs) have been proved to have low toxicity and multi-target characteristics. In the last few decades, an increasing number of studies have demonstrated that TCMs exhibit strong anticancer effects in both experimental and clinical models and may serve as alternative chemotherapy agents for CRC treatment. Notably, Wnt/β-catenin signaling pathway plays a vital role in the initiation and progression of CRC by modulating the stability of β-catenin in the cytoplasm. Targeting Wnt/β-catenin pathway is a novel direction for developing therapies for CRC. In this review, we outlined the anti-tumor effects of small molecular inhibitors on CRC through Wnt/β-catenin pathway. More importantly, we focused on the potential role of TCMs against tumors by targeting Wnt/β-catenin signaling at different stages of CRC, including precancerous lesions, early stage of CRC and advanced CRC. Furthermore, we also discussed perspectives to develop potential new drugs from TCMs via Wnt/β-catenin pathway for the treatment of CRC.

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Interplay between Dietary Polyphenols and Oral and Gut Microbiota in the Development of Colorectal Cancer

Nutrients ◽

10.3390/nu12030625 ◽

2020 ◽

Vol 12 (3) ◽

pp. 625 ◽

Cited By ~ 6

Author(s):

Carolina Cueva ◽

Mariana Silva ◽

Iris Pinillos ◽

Begoña Bartolomé ◽

M. Victoria Moreno-Arribas

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Current Knowledge ◽

Experimental Studies ◽

Oral Bacteria ◽

Intestinal Microbes ◽

Therapeutic Implications ◽

Dietary Polyphenols ◽

Relevant Role

Colorectal cancer (CRC) is the third most diagnosed type of cancer worldwide. Dietary features play an important role in its development, and the involvement of human microbial communities in this pathology has also recently been recognized. Individuals with CRC display alterations in gut bacterial composition and a notably higher abundance of putative oral bacteria in colonic tumors. Many experimental studies and preclinical evidence propose that dietary polyphenols have a relevant role in CRC development and progression, mainly attributed to their immunomodulatory activities. Furthermore, polyphenols can modulate oral and gut microbiota, and in turn, intestinal microbes catabolize polyphenols to release metabolites that are often more active and better absorbed than the original phenolic compounds. The current study aimed to review and summarize current knowledge on the role of microbiota and the interactions between dietary polyphenols and microbiota in relation to CRC development. We have highlighted the mechanisms by which dietary polyphenols and/or their microbial metabolites exert their action on the pathogenesis and prevention of CRC as modulators of the composition and/or activity of oral and intestinal microbiota, including novel screening biomarkers and possible nutritional therapeutic implications.

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