scholarly journals Comparative Carcinogenic Effects of Folic Acid vs. 5-Methyltetrahydrofolate Supplementation on Colon Cancer Progression in a Rodent Model

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1319-1319
Author(s):  
Baljit Kaur ◽  
Carina Chan ◽  
Samantha Yim ◽  
Kyoung-Jin Sohn ◽  
Young-In Kim
Keyword(s):  
Colon Cancer ◽  
Folic Acid ◽  
Cancer Progression ◽  
Control Diet ◽  
Tumor Burden ◽  
Aberrant Crypt Foci ◽  
Tumor Incidence ◽  
Alternative Form ◽  
Folate Supplementation ◽  
Plasma Folate

Abstract Objectives High folic acid (FA) intake may be associated with adverse health outcomes, including colon cancer promotion. 5-methyltetrahydrofolate (5MTHF) has been proposed as a safer alternative form of folate supplementation. We compared the effects of FA and 5MTHF supplementation on the progression of aberrant crypt foci (ACF; earliest colon cancer precursor). Methods Male Sprague Dawley rats (n = 120) received a control diet (1mg FA or equimolar 5MTHF) at weaning and ACF were induced by azoxymethane. Six weeks post-induction, rats were randomized to the control or supplemental (10mg FA or equimolar 5MTHF) diets for 18 weeks. Plasma folate concentrations were assessed using microbiological assay and compared. Colorectal tumor incidence, multiplicity and burden (sum of tumor diameters) were determined and compared. Results 5MTHF resulted in higher plasma folate concentration compared to FA (p < 0.05). Tumor incidence (adenoma, p = 0.5; adenocarcinoma, p = 0.60) did not differ between the folate forms. Both FA and 5MTHF supplementation resulted in a higher number of adenocarcinomas compared to respective controls. 5MTHF groups had higher tumor burden compared to the corresponding levels of FA (p < 0.05). Conclusions 5MTHF resulted in higher tumor burden than FA and was at least as effective as FA in increasing the number of adenocarcinomas in predisposed rats harboring ACF. 5MTHF does not confer a safer alternative to FA supplementation with regards to colon cancer promotion and may in fact have a higher colon tumor promoting effect than FA supplementation. Notwithstanding the inherent limitations associated with animal models, our study suggests that future studies are warranted to compare biochemical and biologic effects and safety of FA and 5MTHF supplementation. Funding Sources Canadian Institutes of Health Research.

Tumor-enhancing effects of cholic acid are exerted on the early stages of colon carcinogenesis via induction of aberrant crypt foci with an enhanced growth phenotype

1998 ◽  
Vol 76 (12) ◽  
pp. 1095-1102 ◽  
Author(s):  
P K Baijal ◽  
E P Clow ◽  
D W Fitzpatrick ◽  
R P Bird
Keyword(s):  
Cholic Acid ◽  
Control Diet ◽  
Colon Carcinogenesis ◽  
Aberrant Crypt Foci ◽  
Tumor Incidence ◽  
Sprague Dawley ◽  
Colonic Tumor ◽  
Sprague Dawley Rats ◽  
Accelerated Growth ◽  
Growth Phenotype

The objective of the study was to establish whether cholic acid (CHA) enhanced colonic tumor incidence in the early phase of carcinogenesis. Male, Sprague-Dawley rats (n = 180) were injected twice with azoxymethane (AOM) (15 mg·kg-1 body weight·week-1, s.c., given 1 week apart). Following the first AOM injection, animals were randomly assigned to two groups, control AIN-93G diet (CON) or control diet containing 0.2% CHA by weight (CHA). Three weeks after the first injection, 20 animals (10 animals/group) were killed and aberrant crypt foci (ACF) were enumerated. The remaining animals were further subdivided and animals randomly assigned to CON or CHA diets, creating four treatments: CON-CON, CON-CHA, CHA-CHA, and CHA-CON. After 3, 12, and 20 weeks (following the first carcinogen injection), the animals were killed and the number and crypt multiplicity of ACF enumerated. Macroscopic tumors were evaluated at week 20. Total ACF were not different between groups. Average crypt multiplicity and medium (4-6 crypts/focus) and large (>= 7 crypts/focus) ACF were greater in CHA-CHA and CHA-CON compared with CON-CON and CON-CHA (p < 0.01). Transient exposure to CHA (CHA-CON) was sufficient to induce development of ACF with an accelerated growth phenotype and elicit a tumor-enhancing effect. CHA-CHA had the highest tumor incidence (82.8%, p < 0.05) followed by CHA-CON (56.7%, p < 0.05), and tumor multiplicity and number of tumors per rat in CHA-CON were similar to CHA-CHA (2.29 and 1.3 versus 2.33 and 1.9, respectively). Delayed intervention with CHA (CON-CHA) produced a tumor outcome similar to CON-CON (31 and 30%, respectively), it did not enhance colonic tumor incidence. Taken collectively these results suggest CHA was effective in enhancing colon carcinogenesis during early phases and ineffective in post-initiation phases.Key words: aberrant crypt foci, cholic acid, colon, tumors.

Hemostatic Factors Support Colitis and Colitis-Associated Colon Cancer

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3079-3079
Author(s):  
Kris A. Steinbrecher ◽  
Netanel Horowitz ◽  
Maureen A. Shaw ◽  
Kelley A. Barney ◽  
Matthew J. Flick ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Tumor Burden ◽  
Colonic Injury ◽  
Integrin Αiibβ3 ◽  
Cytokines And Chemokines ◽  
Hemostatic Factors ◽  
Inflammatory Processes ◽  
The Many ◽  
Mutant Forms

Abstract Inflammatory bowel disease has been recognized as an important risk factor in the development of colon cancer for decades. However, the factors that support the inflammatory response in this setting are not fully defined. Given that activation of the hemostatic system is a consistent feature of colitis, and previous studies have shown that hemostatic factors are key regulators of inflammation in other settings, we hypothesized that the platelet/fibrinogen axis plays an important role in inflammatory colitis. In order to explore whether fibrinogen interactions with leukocytes or platelets contribute to colitis, we challenged gene-targeted mice expressing mutant forms of fibrinogen lacking the binding motifs recognized by the leukocyte integrin αMβ2 (Fibγ390–396A mice) or the platelet integrin αIIbβ3 (FibγΔ5 mice) with dextran sodium sulfate (DSS). The severity of colonic injury and inflammation in Fibγ390–396A mice were dramatically diminished relative to control animals based on multiple histopathological criteria, including edema, erosion/ulceration, crypt loss, and inflammatory cell infiltration. DSS-challenged Fibγ390–396A mice also exhibited significantly diminished circulating levels of the inflammatory cytokine IL-6. These studies support the general conclusion that fibrinogen-αMβ2 interactions are an important determinant of inflammatory processes within the colon. Complementary studies of FibγΔ5 mice suggest that fibrinogen interaction with the platelet integrin αIIbβ3 is also a determinant of colitis-associated pathologies. Here, initial studies of FibγΔ5 mice revealed that the loss of platelet-fibrinogen interactions results in a significant, but counterintuitive, diminution in colitis-associated GI bleeding and weight loss. Fibrinogen-supported platelet deposition and activation are likely to contribute to inflammatory disease processes though multiple mechanisms, but a contribution of the many proinflammatory cytokines and chemokines present within the platelet secretome may be a significant factor. In addition to supporting colitis, hemostatic factors contribute to the more complex process of colitis-associated cancer (CAC) progression. In this regard, it is notable that Fibγ390–396A mice developed significantly fewer colonic adenomas relative to control mice when challenged with a combination of azoxymethane, a DNA alkylator, and DSS. Indeed, ~30% of Fibγ390–396A mice had no discernable adenomas, while penetrance was 100% in control mice. Furthermore, the tumors harvested from Fibγ390–396A mice were significantly smaller than those observed in wild-type mice, resulting in a profound diminution in total tumor burden. These results support the conclusion that the platelet/fibrinogen axis is a major determinant of inflammatory colitis and colitis-associated cancer progression, and therapies designed to disrupt inflammatory pathways at the level of hemostatic factors could be useful in the treatment or prevention of colitis or colitis-associated colon cancer.

Folate Nutritional Status among Psoriasis Patients not Exposed to Antifolate Drug

2020 ◽  
Vol 16 (4) ◽  
pp. 543-553
Author(s):  
Luciana Y. Tomita ◽  
Andréia C. da Costa ◽  
Solange Andreoni ◽  
Luiza K.M. Oyafuso ◽  
Vânia D’Almeida ◽  
...  
Keyword(s):  
Folic Acid ◽  
Linear Regression ◽  
Multiple Linear Regression Model ◽  
Folate Intake ◽  
Serum Folate ◽  
Linear Regression Models ◽  
Cross Sectional ◽  
Folic Acid Fortification ◽  
Plasma Folate ◽  
Psoriasis Severity

Background: Folic acid fortification program has been established to prevent tube defects. However, concern has been raised among patients using anti-folate drug, i.e. psoriatic patients, a common, chronic, autoimmune inflammatory skin disease associated with obesity and smoking. Objective: To investigate dietary and circulating folate, vitamin B12 (B12) and homocysteine (hcy) in psoriatic subjects exposed to the national mandatory folic acid fortification program. Methods: Cross-sectional study using the Food Frequency Questionnaire, plasma folate, B12, hcy and psoriasis severity using the Psoriasis Area and Severity Index score. Median, interquartile ranges (IQRs) and linear regression models were conducted to investigate factors associated with plasma folate, B12 and hcy. Results: 82 (73%) mild psoriasis, 18 (16%) moderate and 12 (11%) severe psoriasis. 58% female, 61% non-white, 31% former smokers, and 20% current smokers. Median (IQRs) were 51 (40, 60) years. Only 32% reached the Estimated Average Requirement of folate intake. Folate and B12 deficiencies were observed in 9% and 6% of the blood sample respectively, but hyperhomocysteinaemia in 21%. Severity of psoriasis was negatively correlated with folate and B12 concentrations. In a multiple linear regression model, folate intake contributed positively to 14% of serum folate, and negative predictors were psoriasis severity, smoking habits and saturated fatty acid explaining 29% of circulating folate. Conclusion: Only one third reached dietary intake of folate, but deficiencies of folate and B12 were low. Psoriasis severity was negatively correlated with circulating folate and B12. Stopping smoking and a folate rich diet may be important targets for managing psoriasis.

Role of MicroRNAs in Colon Cancer Progression and Metastasis

2020 ◽  
Vol 20 ◽  
Author(s):  
Shruthi Sanjitha Sampath ◽  
Sivaramakrishnan Venkatabalsubramanian ◽  
Satish Ramalingam
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Tumour Progression ◽  
Intestinal Barrier ◽  
Colon Cancer Progression ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression

MicroRNA ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 68-75 ◽  
Author(s):  
Jeyalakshmi Kandhavelu ◽  
Kumar Subramanian ◽  
Amber Khan ◽  
Aadilah Omar ◽  
Paul Ruff ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Progression ◽  
Target Prediction ◽  
Computational Prediction ◽  
Initial Step ◽  
Kegg Pathways ◽  
Candidate Mirnas ◽  
Common Cancer ◽  
Colon Cancer Progression

Background:Globally, colorectal cancer (CRC) is the third most common cancer in women and the fourth most common cancer in men. Dysregulation of small non-coding miRNAs have been correlated with colon cancer progression. Since there are increasing reports of candidate miRNAs as potential biomarkers for CRC, this makes it important to explore common miRNA biomarkers for colon cancer. As computational prediction of miRNA targets is a critical initial step in identifying miRNA: mRNA target interactions for validation, we aim here to construct a potential miRNA network and its gene targets for colon cancer from previously reported candidate miRNAs, inclusive of 10 up- and 9 down-regulated miRNAs from tissues; and 10 circulatory miRNAs. </P><P> Methods: The gene targets were predicted using DIANA-microT-CDS and TarBaseV7.0 databases. Each miRNA and its targets were analyzed further for colon cancer hotspot genes, whereupon DAVID analysis and mirPath were used for KEGG pathway analysis.Results:We have predicted 874 and 157 gene targets for tissue and serum specific miRNA candidates, respectively. The enrichment of miRNA revealed that particularly hsa-miR-424-5p, hsa-miR-96-5p, hsa-miR-1290, hsa-miR-224, hsa-miR-133a and has-miR-363-3p present possible targets for colon cancer hallmark genes, including BRAF, KRAS, EGFR, APC, amongst others. DAVID analysis of miRNA and associated gene targets revealed the KEGG pathways most related to cancer and colon cancer. Similar results were observed in mirPath analysis. A new insight gained in the colon cancer network pathway was the association of hsa-mir-133a and hsa-mir-96-5p with the PI3K-AKT signaling pathway. In the present study, target prediction shows that while hsa-mir-424-5p has an association with mostly 10 colon cancer hallmark genes, only their associations with MAP2 and CCND1 have been experimentally validated.These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately with the potential to develop novel therapeutic targets.

scholarly journals INFORM: INFrared-based ORganizational Measurements of tumor and its microenvironment to predict patient survival

2021 ◽  
Vol 7 (6) ◽  
pp. eabb8292
Author(s):  
Saumya Tiwari ◽  
Andre Kajdacsy-Balla ◽  
Joshua Whiteley ◽  
Georgina Cheng ◽  
Stephen M. Hewitt ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Spatial Organization ◽  
Infrared Imaging ◽  
Patient Survival ◽  
High Definition ◽  
Risk Of Death ◽  
Measurement Framework ◽  
Spatially Varying ◽  
Physical And Chemical

The structure and organization of a tumor and its microenvironment are often associated with cancer outcomes due to spatially varying molecular composition and signaling. A persistent challenge is to use this physical and chemical spatial organization to understand cancer progression. Here, we present a high-definition infrared imaging–based organizational measurement framework (INFORM) that leverages intrinsic chemical contrast of tissue to label unique components of the tumor and its microenvironment. Using objective and automated computational methods, further, we determine organization characteristics important for prediction. We show that the tumor spatial organization assessed with this framework is predictive of overall survival in colon cancer that adds to capability from clinical variables such as stage and grade, approximately doubling the risk of death in high-risk individuals. Our results open an all-digital avenue for measuring and studying the association between tumor spatial organization and disease progression.

scholarly journals Proteins are potent biomarkers to detect colon cancer progression

2017 ◽  
Vol 24 (6) ◽  
pp. 1212-1221 ◽  
Author(s):  
Palaniselvam Kuppusamy ◽  
Natanamurugaraj Govindan ◽  
Mashitah M. Yusoff ◽  
Solachuddin J.A. Ichwan
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Colon Cancer Progression

scholarly journals Intermittent Iron Folate Supplementation: Impact on Hematinic Status and Growth of School Girls

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Aditi Sen ◽  
Shubhada Kanani
Keyword(s):  
Body Mass Index ◽  
Folic Acid ◽  
Weekly Dose ◽  
Folate Supplementation ◽  
Standard Methods ◽  
Pubertal Growth ◽  
School Girls ◽  
Iron Folic Acid ◽  
One Year ◽  
The Impact

In view of high iron needs for adolescent growth, this paper studied the impact of daily vs. intermittent (once and twice weekly) iron folic acid (IFA) supplementation on hemoglobin levels and pubertal growth among primary school girls in early adolescence (9–13 years) of Vadodara, India. Methods. Hemoglobin (Hb), height and weight of the girls were assessed using standard methods. In three experimental schools (ES) IFA tablets in a dose of 100 mg Fe+0.5 mg folic acid was given either daily, once weekly or twice weekly for one year. The fourth school (control: CS) did not receive any intervention. Results. Hb levels significantly improved (P<0.01) in all ES compared to CS. Body Mass Index (BMI) increment in ES vs CS was significant (P<0.05) in twice weekly IFA and daily IFA. Within ES groups, mean Hb and BMI increments were comparable between twice weekly IFA and daily IFA. Anemic ES girls showed higher Hb and BMI increments vs. non-anemic girls. Better the Hb response, greater was the benefit on BMI. Conclusion: Twice-weekly IFA supplementation was comparable to daily IFA as regards impact on Hb and growth; at less cost and greater feasibility. Once-weekly dose was inadequate to significantly improve growth.

The upregulation of PYCR2 is associated with aggressive colon cancer progression and a poor prognosis

2021 ◽  
Vol 572 ◽  
pp. 20-26
Author(s):  
Sitong Wang ◽  
Linaer Gu ◽  
Lili Huang ◽  
Juemin Fang ◽  
Zhuqing Liu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Colon Cancer Progression
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