Antioxidant Agents and Colorectal Carcinogenesis: Role of β-Carotene, Vitamin E and Vitamin C

1996 ◽  
Vol 82 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Giuseppe Pappalardo ◽  
Antonio Guadalaxara ◽  
Giuseppe Maiani ◽  
Giovanni Illomei ◽  
Mauro Trifero ◽  
...  

In consideration of findings reported in the literature and of our study, we examined the correlation between antioxidants (β-carotene, vitamin C, vitamin E) and colorectal carcinogenesis. Although diagnostic progress has been made in the last decades, no significant improvements in death rates have been achieved in the western world. Exogenous factors might be responsible for a complex alteration process of normal colonic mucosa into adenoma and carcinoma. Free radicals and reactive oxygen metabolites, due to increased production or to reduced inactivation, following a decrease in the antioxidant burden in the mucosa, might cause damage to DNA, thereby resulting in genetic alterations. This might represent the cause of the transformation process: normal mucosa→ adenoma→ carcinoma. In a prospective study, we observed a reduction of β-carotene levels in normal colonic mucosa in patients with polyps and colorectal cancer. We also showed that β-carotene supplementation raises levels of this micronutrient in the colonic mucosa of these patients. Findings from the literature and our trials show a significant decrease in the antioxidant capacity of colorectal mucosa in patients affected by colorectal cancer, although there is a significant interindividual variability. Such results suggest a possible chemopreventive role of antioxidant agents in colorectal cancer.

2004 ◽  
Vol 287 (1) ◽  
pp. G7-G17 ◽  
Author(s):  
Steven H. Itzkowitz ◽  
Xianyang Yio

Patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer. To date, no known genetic basis has been identified to explain colorectal cancer predisposition in these inflammatory bowel diseases. Instead, it is assumed that chronic inflammation is what causes cancer. This is supported by the fact that colon cancer risk increases with longer duration of colitis, greater anatomic extent of colitis, the concomitant presence of other inflammatory manifestations such as primary sclerosing cholangitis, and the fact that certain drugs used to treat inflammation, such as 5-aminosalicylates and steroids, may prevent the development of colorectal cancer. The major carcinogenic pathways that lead to sporadic colorectal cancer, namely chromosomal instability, microsatellite instability, and hypermethylation, also occur in colitis-associated colorectal cancers. Unlike normal colonic mucosa, however, inflamed colonic mucosa demonstrates abnormalities in these molecular pathways even before any histological evidence of dysplasia or cancer. Whereas the reasons for this are unknown, oxidative stress likely plays a role. Reactive oxygen and nitrogen species produced by inflammatory cells can interact with key genes involved in carcinogenic pathways such as p53, DNA mismatch repair genes, and even DNA base excision-repair genes. Other factors such as NF-κB and cyclooxygenases may also contribute. Administering agents that cause colitis in healthy rodents or genetically engineered cancer-prone mice accelerates the development of colorectal cancer. Mice genetically prone to inflammatory bowel disease also develop colorectal cancer especially in the presence of bacterial colonization. These observations offer compelling support for the role of inflammation in colon carcinogenesis.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Francesco Mariani ◽  
Paola Sena ◽  
Giulia Magnani ◽  
Stefano Mancini ◽  
Carla Palumbo ◽  
...  

Promyelocytic leukemia zinc finger protein (PLZF) is a protein involved in various signaling, growth regulatory, and differentiation pathways, including development/function of some T cells. Here, we aimed at the detection of PLZF during colorectal carcinogenesis, using immunofluorescence, and at the evaluation of the colocalization of PLZF with CD2 and CD56 positive cells (T,γδ, NK, and NKT cells), using confocal-microscopy, along colorectal carcinogenesis, since its earliest stages, that is, dysplastic aberrant crypt foci (ACF). Furthermore, we analyzed PLZF in the normal colonic mucosa (NM) according to anthropometric parameters of the subject. NM exhibited strong CD56 fluorescent staining. This infiltration was lost in both ACF and colorectal carcinoma (CRC), while PLZF presence increased from NM to ACF and CRC. Strong association was found between CD56+ colonic mucosa cell infiltration and body mass index. Interestingly, an increased stromal PLZF-reactivity was present in NM of obese subjects. This study shows that overexpression of PLZF and exclusion of NK cells in dysplastic microenvironment are very early events in the stepwise sequence leading to CRC and that lower levels of CD56+ cells in NM, together with increased levels of PLZF+ cells, can be a reflection of colon cancer risk due to obesity.


Author(s):  
Sridhar Muthusami ◽  
Ilangovan Ramachandran ◽  
Sneha Krishnamoorthy ◽  
Yuvaraj Sambandam ◽  
Satish Ramalingam ◽  
...  

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.


2019 ◽  
Vol 22 (10) ◽  
pp. 1872-1887 ◽  
Author(s):  
Ahmad Jayedi ◽  
Ali Rashidy-Pour ◽  
Mohammad Parohan ◽  
Mahdieh Sadat Zargar ◽  
Sakineh Shab-Bidar

AbstractObjectiveThe present review aimed to quantify the association of dietary intake and circulating concentration of major dietary antioxidants with risk of total CVD mortality.DesignSystematic review and meta-analysis.SettingSystematic search in PubMed and Scopus, up to October 2017.ParticipantsProspective observational studies reporting risk estimates of CVD mortality across three or more categories of dietary intakes and/or circulating concentrations of vitamin C, vitamin E and β-carotene were included. A random-effects meta-analysis was conducted.ResultsA total of fifteen prospective cohort studies and three prospective evaluations within interventional studies (320 548 participants and 16 974 cases) were analysed. The relative risks of CVD mortality for the highest v. the lowest category of antioxidant intakes were as follows: vitamin C, 0·79 (95 % CI 0·68, 0·89; I2=46 %, n 10); vitamin E, 0·91 (95 % CI 0·79, 1·03; I2=51 %, n 8); β-carotene, 0·89 (95 % CI 0·73, 1·05; I2=34 %, n 4). The relative risks for circulating concentrations were: vitamin C, 0·60 (95 % CI 0·42, 0·78; I2=65 %, n 6); α-tocopherol, 0·82 (95 % CI 0·76, 0·88; I2=0 %, n 5); β-carotene, 0·68 (95 % CI 0·52, 0·83; I2=50 %, n 6). Dose–response meta-analyses demonstrated that the circulating biomarkers of antioxidants were more strongly associated with risk of CVD mortality than dietary intakes.ConclusionsThe present meta-analysis demonstrates that higher vitamin C intake and higher circulating concentrations of vitamin C, vitamin E and β-carotene are associated with a lower risk of CVD mortality.


2009 ◽  
Vol 27 (2) ◽  
pp. 186-192 ◽  
Author(s):  
Paul Salama ◽  
Michael Phillips ◽  
Fabienne Grieu ◽  
Melinda Morris ◽  
Nik Zeps ◽  
...  

Purpose To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3+ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer.


2005 ◽  
Vol 48 (7) ◽  
pp. 993-1001 ◽  
Author(s):  
Rulian Ricardo Faria ◽  
Vanessa Costhek Abílio ◽  
Christian Grassl ◽  
Cibele Cristina Chinen ◽  
Luciana Takahashi Ribeiro Negrão ◽  
...  

2021 ◽  
Vol 22 (16) ◽  
pp. 8470
Author(s):  
Hui Wang ◽  
Tian Tian ◽  
Jinhua Zhang

Colorectal cancer (CRC) is a malignant tumor in the digestive system whose incidence and mortality is high-ranking among tumors worldwide. The initiation and progression of CRC is a complex process involving genetic alterations in cancer cells and multiple factors from the surrounding tumor cell microenvironment. As accumulating evidence has shown, tumor-associated macrophages (TAMs)—as abundant and active infiltrated inflammatory cells in the tumor microenvironment (TME)—play a crucial role in CRC. This review focuses on the different mechanisms of TAM in CRC, including switching of phenotypical subtypes; promoting tumor proliferation, invasion, and migration; facilitating angiogenesis; mediating immunosuppression; regulating metabolism; and interacting with the microbiota. Although controversy remains in clinical evidence regarding the role of TAMs in CRC, clarifying their significance in therapy and the prognosis of CRC may shed new light on the optimization of TAM-centered approaches in clinical care.


Author(s):  
Ekaterina Statsenko ◽  
Oksana Litvinenko ◽  
Nadezhda Korneva ◽  
Mikhail Shtarberg ◽  
Evgeniy Borodin

Abstract. Introduction. Domestic food production based on the regional market characteristics can expand the range of functional foods. The research objective was to develop a new technology for desserts based on soy and pumpkin. Study objects and methods. The research featured soybeans of the “Yurna” variety and pumpkin of the “Nadezhda” variety. Soaked soybeans were mixed with mashed pumpkin and drinking water. The mass was heated and kept at 100°C for 30 min with simultaneous grinding and extraction of soluble dry matter. The soy and pumpkin liquid fraction was separated by filtration. A 2.5% aqueous solution of ascorbic acid was added to the liquid fraction at 75–80°C to coagulate protein and other substances. The soy and pumpkin coagulate had a moisture content of 75.0 ± 1%. It was mixed with sea buckthorn syrup and homogenized. The finished product was called “Nadezhda+”. The “Nezhnyi” dessert consisted of gelling solution mixed with soy and pumpkin coagulate and sea buckthorn syrup, after which the mass was homogenized. Results and discussion. The expert assessment helped to identify the most significant indicators of the sensory evaluation of the desserts, namely taste and consistency. The sensory evaluation also made it possible to define the optimal homogenization time for the mix: 60 s for “Nadezhda+” and 90 s for “Nezhnyi”. The developed desserts contained protein (5.75 and 4.70 g/100 g), phosphatides (334 and 102 mg/100 g), β-carotene (2.86 and 1.62 mg/100 g), vitamin E (28.60 and 16.00 mg/100 g) and vitamin C (35.10 and 10.60 mg/100 g), respectively. Conclusion. The content of β-carotene and vitamin E exceeded 15 % of the daily intake in one portion (100 g) of the desserts, as well as vitamin C in “Nadezhda+”. According with State Standard R 52349-2005, the new desserts could be referred to functional foods.


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