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

2013 ◽  
Vol 62 (8) ◽  
pp. 1107-1123 ◽  
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.

scholarly journals Chemokines—What Is Their Role in Colorectal Cancer?

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338 ◽  
Author(s):  
Sara Pączek ◽  
Marta Łukaszewicz-Zając ◽  
Barbara Mroczko
Keyword(s):  
Colorectal Cancer ◽  
Current Knowledge ◽  
Early Stage ◽  
Distant Metastases ◽  
Cell Types ◽  
Diagnosis And Prognosis ◽  
Novel Biomarkers ◽  
Specific Receptors ◽  
Common Malignancy

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.

Diffuse scattering in protein crystallography

1995 ◽  
Vol 28 (2) ◽  
pp. 131-169 ◽  
Author(s):  
Jean-Pierre Benoit ◽  
Jean Doucet
Keyword(s):  
Molecular Biology ◽  
Active Site ◽  
Diffuse Scattering ◽  
Three Dimensional ◽  
X Ray Diffraction ◽  
X Ray ◽  
Physico Chemical ◽  
Chemical Conditions ◽  
Functional Mechanisms

The understanding of flexibility and deformability in proteins is one of the current major challenges of structural molecular biology. The knowledge of the average atomic positions of three-dimensional folding of proteins, which is obtained either by X-ray diffraction or n.m.r. spectroscopy, is generally not sufficient to explain their functional mechanisms. Very often it is necessary to consider the existence of other concerted atomic motions as, for example, in the well-known case of the CO molecule fixation at the active site of myoglobin which requires the concerted displacement of a large number of atoms in order to open a channel down to this site. This opening, which depends on the physico-chemical conditions, plays the role of a regulator in the biochemical reactions (Janin & Wodak, 1983; Tainer et al. 1984; Westhof et al. 1984; Ormos et al. 1988).

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

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

scholarly journals Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents

2021 ◽  
Vol 22 (22) ◽  
pp. 12409
Author(s):  
Jelena Vekic ◽  
Aleksandra Zeljkovic ◽  
Aleksandra Stefanovic ◽  
Rosaria Vincenza Giglio ◽  
Marcello Ciaccio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Epidemiological Data ◽  
Beneficial Effects ◽  
Ldl Particles ◽  
Chronic Hyperglycemia

Epidemiological data have demonstrated a significant association between the presence of type 2 diabetes mellitus (T2DM) and the development of colorectal cancer (CRC). Chronic hyperglycemia, insulin resistance, oxidative stress, and inflammation, the processes inherent to T2DM, also play active roles in the onset and progression of CRC. Recently, small dense low-density lipoprotein (LDL) particles, a typical characteristic of diabetic dyslipidemia, emerged as another possible underlying link between T2DM and CRC. Growing evidence suggests that antidiabetic medications may have beneficial effects in CRC prevention. According to findings from a limited number of preclinical and clinical studies, glucagon-like peptide-1 receptor agonists (GLP-1RAs) could be a promising strategy in reducing the incidence of CRC in patients with diabetes. However, available findings are inconclusive, and further studies are required. In this review, novel evidence on molecular mechanisms linking T2DM with CRC development, progression, and survival will be discussed. In addition, the potential role of GLP-1RAs therapies in CRC prevention will also be evaluated.

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

2019 ◽  
Vol 9 (1) ◽  
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.

scholarly journals Fibre and colorectal cancer: a controversial question

2006 ◽  
Vol 96 (S1) ◽  
pp. S46-S48 ◽  
Author(s):  
Antoni Obrador
Keyword(s):  
Colorectal Cancer ◽  
Dietary Fibre ◽  
Protective Factor ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Colorectal Polyps ◽  
Daily Consumption ◽  
Beneficial Effects ◽  
Intervention Trials

Since the 1970s it has been postulated that dietary fibre is a protective factor against colorectal cancer. Several epidemiological studies have been performed following different designs (correlation studies, case–control, cohort) and overall they have supported the hypothesis of a benefit of dietary fibre. However, a few intervention trials have not demonstrated the preventive role of dietary fibre on the occurrence of adenomatous colorectal polyps. Nevertheless, there are multiple animal experimental studies that support the role of fibre in the prevention of colorectal cancer. In the present review, the most important contributions to this controversial question are revised. Finally, it is recommended to continue encouraging an increase in the daily consumption of fibre, since it probably plays an important role in the prevention of colorectal cancer, together with other beneficial effects.

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

2015 ◽  
Vol 57 (11) ◽  
pp. 2310-2320 ◽  
Author(s):  
C. H. Little ◽  
E. Combet ◽  
D. C. McMillan ◽  
P. G. Horgan ◽  
C. S. D. Roxburgh
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Response ◽  
Early Stage ◽  
Dietary Polyphenols

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

Cancers ◽  
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.

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

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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