1024 Transcriptional Response to 1,25(OH)2 Vitamin D in the Human Colon: Differences by Ethnicity and Colorectal Cancer Affection

2014 ◽  
Vol 146 (5) ◽  
pp. S-181
Author(s):  
Sonia Kupfer ◽  
David Witonsky ◽  
Meredith Chase ◽  
Katy Ceryes ◽  
Anna DiRienzo
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Transcriptional Response ◽  
Human Colon

scholarly journals Ex vivo culture of primary human colonic tissue for studying transcriptional responses to 1α,25(OH)2 and 25(OH) vitamin D

2014 ◽  
Vol 46 (8) ◽  
pp. 302-308 ◽  
Author(s):  
Brandon Mapes ◽  
Meredith Chase ◽  
Ellie Hong ◽  
Anton Ludvik ◽  
Katy Ceryes ◽  
...  
Keyword(s):  
Vitamin D ◽  
Ex Vivo ◽  
Transcriptional Response ◽  
Human Colon ◽  
Colonic Tissue ◽  
Short Term ◽  
Transcriptional Responses ◽  
Dihydroxyvitamin D ◽  
25 Oh Vitamin D ◽  
Ex Vivo Culture

1α,25-Dihydroxyvitamin D3 [1α,25(OH)2D3] is a steroid hormone derived from circulating 25(OH) vitamin D [25(OH)D] with chemopreventive effects in colorectal cancer. 1α,25(OH)2D3 acts through transcriptional mechanisms; however, our understanding of vitamin D transcriptional responses in the colon is derived from studies in transformed cancer cell lines which may not represent responses in normal healthy tissue. Here, we describe the optimization of an ex vivo culture model using primary colonic biopsy samples for studying short-term transcriptional response induced by 1α,25(OH)2D3 and 25(OH)D treatment. Colon biopsy samples from healthy subjects were maintained in primary culture and treated in parallel with 100 nM 1α,25(OH)2D3 or 62.5 nM 25(OH)D and vehicle control (ethanol). Viability was assessed using histology and enzymatic assays. Genome-wide transcriptional responses to 1α,25(OH)2D3 were assessed and expression of 25(OH)D targets CYP27B1 and CYP24A1 were measured by real time PCR. We show that ex vivo culture of colonic tissue remains viable for up to 8 h. The largest number of differentially expressed genes in response to 1α,25(OH)2D3 was noted after 6 h ( n = 120). As proof of concept, the top upregulated gene was CYP24A1, a well-established vitamin D-responsive gene. With 25(OH)D treatment, mRNA expression of CYP27B1 was significantly increased after 1 h, while expression of CYP24A1 was greatest at 8 h. Ex vivo culture can be used to assess short-term transcriptional responses to 1α,25(OH)2D3 and 25(OH)D in primary tissue from human colon. Future studies will address interindividual differences in transcriptional responses.

scholarly journals RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3192
Author(s):  
Antoine Gleizes ◽  
Mouna Triki ◽  
Sandrine Bonnet ◽  
Naomi Baccari ◽  
Gabriel Jimenez-Dominguez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Differentiation ◽  
Paneth Cell ◽  
Wnt Signaling Pathway ◽  
Cell Lineage ◽  
Human Colon ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Sox9 Expression ◽  
Human Colon Cancer

RIP140 is a major transcriptional coregulator of gut homeostasis and tumorigenesis through the regulation of Wnt/APC signaling. Here, we investigated the effect of RIP140 on Paneth cell differentiation and its interplay with the transcription factor SOX9. Using loss of function mouse models, human colon cancer cells, and tumor microarray data sets we evaluated the role of RIP140 in SOX9 expression and activity using RT-qPCR, immunohistochemistry, luciferase reporter assays, and GST-pull down. We first evidence that RIP140 strongly represses the Paneth cell lineage in the intestinal epithelium cells by inhibiting Sox9 expression. We then demonstrate that RIP140 interacts with SOX9 and inhibits its transcriptional activity. Our results reveal that the Wnt signaling pathway exerts an opposite regulation on SOX9 and RIP140. Finally, the levels of expression of RIP140 and SOX9 exhibit a reverse response and prognosis value in human colorectal cancer biopsies. This work highlights an intimate transcriptional cross-talk between RIP140 and SOX9 in intestinal physiopathology.

scholarly journals Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helena de Castro e Gloria ◽  
Laura Jesuíno Nogueira ◽  
Patrícia Bencke Grudzinski ◽  
Paola Victória da Costa Ghignatti ◽  
Temenouga Nikolova Guecheva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Mismatch Repair ◽  
Cell Cycle Progression ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Human Colon ◽  
Human Colon Cancer

Abstract Background The advances in colorectal cancer (CRC) treatment include the identification of deficiencies in Mismatch Repair (MMR) pathway to predict the benefit of adjuvant 5-fluorouracil (5-FU) and oxaliplatin for stage II CRC and immunotherapy. Defective MMR contributes to chemoresistance in CRC. A growing body of evidence supports the role of Poly-(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, in the treatment of different subsets of cancer beyond the tumors with homologous recombination deficiencies. In this work we evaluated the effect of Olaparib on 5-FU cytotoxicity in MMR-deficient and proficient CRC cells and the mechanisms involved. Methods Human colon cancer cell lines, proficient (HT29) and deficient (HCT116) in MMR, were treated with 5-FU and Olaparib. Cytotoxicity was assessed by MTT and clonogenic assays, apoptosis induction and cell cycle progression by flow cytometry, DNA damage by comet assay. Adhesion and transwell migration assays were also performed. Results Our results showed enhancement of the 5-FU citotoxicity by Olaparib in MMR-deficient HCT116 colon cancer cells. Moreover, the combined treatment with Olaparib and 5-FU induced G2/M arrest, apoptosis and polyploidy in these cells. In MMR proficient HT29 cells, the Olaparib alone reduced clonogenic survival, induced DNA damage accumulation and decreased the adhesion and migration capacities. Conclusion Our results suggest benefits of Olaparib inclusion in CRC treatment, as combination with 5-FU for MMR deficient CRC and as monotherapy for MMR proficient CRC. Thus, combined therapy with Olaparib could be a strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.

Associations of vitamin D status with colorectal cancer risk and survival

2021 ◽  
Author(s):  
Jian Zhou ◽  
Xianxiu Ge ◽  
Xikang Fan ◽  
Jiayu Wang ◽  
Lin Miao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cancer Risk ◽  
Colorectal Cancer Risk ◽  
Vitamin D Status

scholarly journals Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vidya Lakshmi Purushothaman ◽  
Raphael E. Cuomo ◽  
Cedric F. Garland ◽  
Timothy K. Mackey
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Age Groups ◽  
Incidence Rates ◽  
Ultraviolet B ◽  
Inverse Association ◽  
Crude Incidence ◽  
Age Dependent ◽  
Uvb Exposure

Abstract Background Vitamin D has been identified as a potential protective factor in the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally. Methods In this ecological study, a series of linear and polynomial regression tests were performed between country-specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps. Results The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates. Conclusion The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population-wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.

scholarly journals Prevalence of vitamin D deficiency in Chinese patients with early stage colorectal cancer

2018 ◽  
Vol 29 ◽  
pp. ix41
Author(s):  
D. Ng ◽  
R. Tan ◽  
R. Sultana ◽  
M. Ang ◽  
W. Lim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Early Stage ◽  
Chinese Patients

scholarly journals Calcium and Vitamin D Intake and Risk of Colorectal Cancer: The Multiethnic Cohort Study

2007 ◽  
Vol 165 (7) ◽  
pp. 784-793 ◽  
Author(s):  
S.-Y. Park ◽  
S. P. Murphy ◽  
L. R. Wilkens ◽  
A. M. Y. Nomura ◽  
B. E. Henderson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cohort Study ◽  
Vitamin D Intake ◽  
Multiethnic Cohort

scholarly journals Serum vitamin D levels and survival of patients with colorectal cancer: Post-hoc analysis of a prospective cohort study

BMC Cancer ◽  
2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Hidetoshi Mezawa ◽  
Tsutomu Sugiura ◽  
Michiaki Watanabe ◽  
Chihiro Norizoe ◽  
Daisuke Takahashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Serum Vitamin ◽  
Post Hoc Analysis ◽  
Serum Vitamin D ◽  
Vitamin D Levels ◽  
Post Hoc
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