, a bio/informatics shared resource is still "open for business" - Visit the CDS website


Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 333

Publication Record

Connections

Increased Epithelial Oxygenation Links Colitis to an Expansion of Tumorigenic Bacteria.
Cevallos SA, Lee JY, Tiffany CR, Byndloss AJ, Johnston L, Byndloss MX, Bäumler AJ
(2019) mBio 10:
MeSH Terms: Aerobiosis, Animals, Carcinogenesis, Colitis, Colorectal Neoplasms, Dextran Sulfate, Escherichia coli, Escherichia coli Infections, Female, Gastrointestinal Microbiome, Mice, Mice, Inbred C57BL, Oxygen, Peptides, Polyketides
Show Abstract · Added March 30, 2020
Intestinal inflammation is a risk factor for colorectal cancer formation, but the underlying mechanisms remain unknown. Here, we investigated whether colitis alters the colonic microbiota to enhance its cancer-inducing activity. Colitis increased epithelial oxygenation in the colon of mice and drove an expansion of within the gut-associated microbial community through aerobic respiration. An aerobic expansion of colibactin-producing was required for the cancer-inducing activity of this pathobiont in a mouse model of colitis-associated colorectal cancer formation. We conclude that increased epithelial oxygenation in the colon is associated with an expansion of a prooncogenic driver species, thereby increasing the cancer-inducing activity of the microbiota. One of the environmental factors important for colorectal cancer formation is the gut microbiota, but the habitat filters that control its cancer-inducing activity remain unknown. Here, we show that chemically induced colitis elevates epithelial oxygenation in the colon, thereby driving an expansion of colibactin-producing , a prooncogenic driver species. These data suggest that elevated epithelial oxygenation is a potential risk factor for colorectal cancer formation because the consequent changes in the gut habitat escalate the cancer-inducing activity of the microbiota.
Copyright © 2019 Cevallos et al.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Management of Inflammatory Bowel Disease-Associated Dysplasia in the Modern Era.
Shah SC, Itzkowitz SH
(2019) Gastrointest Endosc Clin N Am 29: 531-548
MeSH Terms: Colorectal Neoplasms, Disease Management, Humans, Hyperplasia, Inflammatory Bowel Diseases, Intestines, Precancerous Conditions, Quality of Life, Risk Factors
Show Abstract · Added March 3, 2020
This article begins with a brief overview of risk factors for colorectal neoplasia in inflammatory bowel disease to concretize the approach to risk stratification. It then provides an up-to-date review of diagnosis and management of dysplasia in inflammatory bowel disease, which integrates new and emerging data in the field. This is particularly relevant in an era of increased attention to cost- and resource-containment from the health systems vantage point, coupled with a heightened prioritization of patient quality of life and shared decision-making. Also provided is a brief discussion of the status of newer therapeutic techniques, such as endoscopic submucosal dissection.
Copyright © 2019 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
Serine Threonine Kinase 17A Maintains the Epithelial State in Colorectal Cancer Cells.
Short SP, Thompson JJ, Bilotta AJ, Chen X, Revetta FL, Washington MK, Williams CS
(2019) Mol Cancer Res 17: 882-894
MeSH Terms: Apoptosis Regulatory Proteins, Cell Line, Tumor, Cell Movement, Colorectal Neoplasms, Epithelial Cells, Epithelial-Mesenchymal Transition, Fluorouracil, HCT116 Cells, Humans, Neoplasm Metastasis, Protein-Serine-Threonine Kinases
Show Abstract · Added April 15, 2019
Serine threonine kinase 17A (STK17A) is a ubiquitously expressed kinase originally identified as a regulator of apoptosis; however, whether it functionally contributes to colorectal cancer has not been established. Here, we have analyzed STK17A in colorectal cancer and demonstrated decreased expression of STK17A in primary tumors, which is further reduced in metastatic lesions, indicating a potential role in regulating the metastatic cascade. Interestingly, changes in STK17A expression did not modify proliferation, apoptosis, or sensitivity of colorectal cancer cell lines to treatment with the chemotherapeutic 5-fluorouracil. Instead, knockdown induced a robust mesenchymal phenotype consistent with the epithelial-mesenchymal transition, including spindle-like cell morphology, decreased expression of adherens junction proteins, and increased migration and invasion. Additionally, overexpression of decreased cell size and induced widespread membrane blebbing, a phenotype often associated with activation of cell contractility. Indeed, STK17A-overexpressing cells displayed heightened phosphorylation of myosin light chain in a manner dependent on STK17A catalytic activity. Finally, patient-derived tumor organoid cultures were used to more accurately determine STK17A's effect in primary human tumor cells. Loss of STK17A induced morphologic changes, decreased E-cadherin, increased invasion, and augmented organoid attachment on 2D substrates, all together suggesting a more metastatic phenotype. Collectively, these data indicate a novel role for STK17A in the regulation of epithelial phenotypes and indicate its functional contribution to colorectal cancer invasion and metastasis. IMPLICATIONS: Loss of serine threonine kinase 17A occurs in colorectal cancer metastasis, induces mesenchymal morphologies, and contributes to tumor cell invasion and migration in colorectal cancer.
©2019 American Association for Cancer Research.
0 Communities
1 Members
0 Resources
11 MeSH Terms
Is a Tumor Suppressor Gene in Colorectal Cancer.
Chen MS, Lo YH, Chen X, Williams CS, Donnelly JM, Criss ZK, Patel S, Butkus JM, Dubrulle J, Finegold MJ, Shroyer NF
(2019) Mol Cancer Res 17: 697-708
MeSH Terms: Animals, Cell Line, Tumor, Colorectal Neoplasms, DNA-Binding Proteins, Genes, Tumor Suppressor, HCT116 Cells, HEK293 Cells, Heterografts, Humans, Male, Mice, Mice, Inbred NOD, Transcription Factors
Show Abstract · Added April 15, 2019
Colorectal cancer is the third most common cancer and the third leading cause of cancer death in the United States. Growth factor-independent 1 (GFI1) is a zinc finger transcriptional repressor responsible for controlling secretory cell differentiation in the small intestine and colon. GFI1 plays a significant role in the development of human malignancies, including leukemia, lung cancer, and prostate cancer. However, the role of GFI1 in colorectal cancer progression is largely unknown. Our results demonstrate that RNA and protein expression of GFI1 are reduced in advanced-stage nonmucinous colorectal cancer. Subcutaneous tumor xenograft models demonstrated that the reexpression of GFI1 in 4 different human colorectal cancer cell lines inhibits tumor growth. To further investigate the role of Gfi1 in colorectal tumorigenesis, we developed transgenic mice harboring a deletion of Gfi1 in the colon driven by CDX2-cre (Gfi1; CDX2-cre) and crossed them with Apc mice (Apc; Gfi1; CDX2-cre). Loss of Gfi1 significantly increased the total number of colorectal adenomas compared with littermate controls with an APC mutation alone. Furthermore, we found that compound (Apc; Gfi1; CDX2-cre) mice develop larger adenomas, invasive carcinoma, as well as hyperplastic lesions expressing the neuroendocrine marker chromogranin A, a feature that has not been previously described in APC-mutant tumors in mice. Collectively, these results demonstrate that acts as a tumor suppressor gene in colorectal cancer, where deficiency of Gfi1 promotes malignancy in the colon. IMPLICATIONS: These findings reveal that GFI1 functions as a tumor suppressor gene in colorectal tumorigenesis.
©2019 American Association for Cancer Research.
0 Communities
1 Members
0 Resources
13 MeSH Terms
No Association Between Pseudopolyps and Colorectal Neoplasia in Patients With Inflammatory Bowel Diseases.
Mahmoud R, Shah SC, Ten Hove JR, Torres J, Mooiweer E, Castaneda D, Glass J, Elman J, Kumar A, Axelrad J, Ullman T, Colombel JF, Oldenburg B, Itzkowitz SH, Dutch Initiative on Crohn and Colitis
(2019) Gastroenterology 156: 1333-1344.e3
MeSH Terms: Adult, Biopsy, Colectomy, Colitis, Ulcerative, Colonic Polyps, Colonoscopy, Colorectal Neoplasms, Crohn Disease, Early Detection of Cancer, Female, Humans, Male, Middle Aged, Neoplasm Grading, Netherlands, New York City, Prevalence, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors
Show Abstract · Added March 3, 2020
BACKGROUND & AIMS - Patients with inflammatory bowel diseases who have postinflammatory polyps (PIPs) have an increased risk of colorectal neoplasia (CRN). European guidelines propose that patients with PIPs receive more frequent surveillance colonoscopies, despite limited evidence of this increased risk. We aimed to define the risk of CRN and colectomy in patients with inflammatory bowel diseases and PIPs.
METHODS - We conducted a multicenter retrospective cohort study of patients with inflammatory bowel diseases who underwent colonoscopic surveillance for CRN, from January 1997 through January 2017, at 5 academic hospitals and 2 large nonacademic hospitals in New York or the Netherlands. Eligible patients had confirmed colonic disease with duration of at least 8 years (or any duration, if they also had primary sclerosing cholangitis) and no history of advanced CRN (high-grade dysplasia or colorectal cancer) or colectomy. The primary outcome was occurrence of advanced CRN according to PIP status; secondary outcomes were occurrence of CRN (inclusive of low-grade dysplasia) and colectomy.
RESULTS - Of 1582 eligible patients, 462 (29.2%) had PIPs. PIPs were associated with more severe inflammation (adjusted odds ratio 1.32; 95% confidence interval [CI] 1.13-1.55), greater disease extent (adjusted odds ratio 1.92; 95% CI 1.34-2.74), and lower likelihood of primary sclerosing cholangitis (adjusted odds ratio 0.38; 95% CI 0.26-0.55). During a median follow-up period of 4.8 years, the time until development of advanced CRN did not differ significantly between patients with and those without PIPs. PIPs did not independently increase the risk of advanced CRN (adjusted hazard ratio 1.17; 95% CI 0.59-2.31). The colectomy rate was significantly higher in patients with PIPs (P = .01).
CONCLUSIONS - In a retrospective analysis of data from 2 large independent surveillance cohorts, PIPs were associated with greater severity and extent of colon inflammation and higher rates of colectomy, but were not associated with development of any degree of CRN. Therefore, intervals for surveillance should not be shortened based solely on the presence of PIPs.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
Statin Exposure Is Not Associated with Reduced Prevalence of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease.
Shah SC, Glass J, Giustino G, Hove JRT, Castaneda D, Torres J, Kumar A, Elman J, Ullman TA, Itzkowitz SH
(2019) Gut Liver 13: 54-61
MeSH Terms: Adult, Cholangitis, Sclerosing, Cohort Studies, Colitis, Colonoscopy, Colorectal Neoplasms, Early Detection of Cancer, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Inflammatory Bowel Diseases, Male, Middle Aged, Population Surveillance, Prevalence, Risk Factors, Time Factors
Show Abstract · Added March 3, 2020
Background/Aims - Statins have been postulated to lower the risk of colorectal neoplasia. No studies have examined any possible chemopreventive effect of statins in patients with inflammatory bowel disease (IBD) undergoing colorectal cancer (CRC) surveillance. This study examined the association of statin exposure with dysplasia and CRC in patients with IBD undergoing dysplasia surveillance colonoscopies.
Methods - A cohort of patients with IBD undergoing colonoscopic surveillance for dysplasia and CRC at a single academic medical center were studied. The inclusion criteria were IBD involving the colon for ≥8 years (or any colitis duration if associated with primary sclerosing cholangitis [PSC]) and at least two colonoscopic surveillance exams. The exclusion criteria were CRC or high-grade dysplasia (HGD) prior to or at enrollment, prior colectomy, or limited (<30%) colonic disease. The primary outcome was the frequency of dysplasia and/or CRC in statin-exposed versus nonexposed patients.
Results - A total of 642 patients met the inclusion criteria (57 statin-exposed and 585 nonexposed). The statin-exposed group had a longer IBD duration, longer follow-up period, and more colonoscopies but lower inflammatory scores, less frequent PSC and less use of thiopurines and biologics. There were no differences in low-grade dysplasia, HGD, or CRC development during the follow-up period between the statin-exposed and nonexposed groups (21.1%, 5.3%, 1.8% vs 19.2%, 2.9%, 2.9%, respectively). Propensity score analysis did not alter the overall findings.
Conclusions - In IBD patients undergoing surveillance colonoscopies, statin use was not associated with reduced dysplasia or CRC rates. The role of statins as chemopreventive agents in IBD remains controversial.
0 Communities
1 Members
0 Resources
MeSH Terms
Serologic Response to Helicobacter pylori Proteins Associated With Risk of Colorectal Cancer Among Diverse Populations in the United States.
Butt J, Varga MG, Blot WJ, Teras L, Visvanathan K, Le Marchand L, Haiman C, Chen Y, Bao Y, Sesso HD, Wassertheil-Smoller S, Ho GYF, Tinker LE, Peek RM, Potter JD, Cover TL, Hendrix LH, Huang LC, Hyslop T, Um C, Grodstein F, Song M, Zeleniuch-Jacquotte A, Berndt S, Hildesheim A, Waterboer T, Pawlita M, Epplein M
(2019) Gastroenterology 156: 175-186.e2
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Bacterial, Bacterial Proteins, Biomarkers, Case-Control Studies, Colorectal Neoplasms, Female, Helicobacter Infections, Helicobacter pylori, Host-Pathogen Interactions, Humans, Incidence, Male, Middle Aged, Prospective Studies, Risk Factors, Seroepidemiologic Studies, United States, Virulence, Young Adult
Show Abstract · Added February 7, 2019
BACKGROUND & AIMS - Previous studies reported an association of the bacteria Helicobacter pylori, the primary cause of gastric cancer, and risk of colorectal cancer (CRC). However, these findings have been inconsistent, appear to vary with population characteristics, and may be specific for virulence factor VacA. To more thoroughly evaluate the potential association of H pylori antibodies with CRC risk, we assembled a large consortium of cohorts representing diverse populations in the United States.
METHODS - We used H pylori multiplex serologic assays to analyze serum samples from 4063 incident cases of CRC, collected before diagnosis, and 4063 matched individuals without CRC (controls) from 10 prospective cohorts for antibody responses to 13 H pylori proteins, including virulence factors VacA and CagA. The association of seropositivity to H pylori proteins, as well as protein-specific antibody level, with odds of CRC was determined by conditional logistic regression.
RESULTS - Overall, 40% of controls and 41% of cases were H pylori-seropositive (odds ratio [OR], 1.09; 95% CI, 0.99-1.20). H pylori VacA-specific seropositivity was associated with an 11% increased odds of CRC (OR, 1.11; 95% CI, 1.01-1.22), and this association was particularly strong among African Americans (OR, 1.45; 95% CI, 1.08-1.95). Additionally, odds of CRC increased with level of VacA antibody in the overall cohort (P = .008) and specifically among African Americans (P = .007).
CONCLUSIONS - In an analysis of a large consortium of cohorts representing diverse populations, we found serologic responses to H pylori VacA to associate with increased risk of CRC risk, particularly for African Americans. Future studies should seek to understand whether this marker is related to virulent H pylori strains carried in these populations.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
Associations among histological characteristics and patient outcomes in colorectal carcinoma with a mucinous component.
Gonzalez RS, Cates JMM, Washington K
(2019) Histopathology 74: 406-414
MeSH Terms: Adenocarcinoma, Mucinous, Adolescent, Adult, Aged, Aged, 80 and over, Child, Colorectal Neoplasms, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Proportional Hazards Models, Young Adult
Show Abstract · Added November 1, 2018
AIMS - Colorectal carcinoma (CRC) often has a mucinous component, with more than 50% mucin by volume defining the mucinous subtype of CRC. The prognostic impact of the mucinous phenotype remains unclear.
METHODS AND RESULTS - We evaluated 224 CRC with at least 5% mucinous component (herein 'mCRC') for patient sex, age, race and outcome; tumour size, location, stage and microsatellite instability (MSI) status; percentage of glands producing mucin; percentage of tumour volume composed of mucin; whether tumoral epithelium floated in mucin pools; tumour budding; signet ring cells (SRCs); and peritumoural inflammation (PI). We related these features to disease-specific survival and compared outcomes to 499 stage-matched, conventional colorectal adenocarcinomas. Factors predicting worse prognosis in mCRC on univariable analysis included non-MSI-high status (P = 0.0008), SRC (P = 0.0017) and lack of PI (P = 0.0034). No parameters were independently associated with outcome after adjusting for tumour stage in multivariate analysis. The percentage of glands producing mucin and percentage tumour volume composed of mucin did not affect prognosis, including at the recommended 50% cut-off for subtyping mCRC. Disease-specific survival for mCRC and adenocarcinomas were similar after accounting for stage.
CONCLUSIONS - Stage-matched mCRCs and adenocarcinomas have similar outcomes, with no prognostic significance to morphological subtyping. Histological characteristics of mCRC, including percentage of tumour volume comprised of mucin, were not predictive of outcome.
© 2018 John Wiley & Sons Ltd.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Epithelial Smad4 Deletion Up-Regulates Inflammation and Promotes Inflammation-Associated Cancer.
Means AL, Freeman TJ, Zhu J, Woodbury LG, Marincola-Smith P, Wu C, Meyer AR, Weaver CJ, Padmanabhan C, An H, Zi J, Wessinger BC, Chaturvedi R, Brown TD, Deane NG, Coffey RJ, Wilson KT, Smith JJ, Sawyers CL, Goldenring JR, Novitskiy SV, Washington MK, Shi C, Beauchamp RD
(2018) Cell Mol Gastroenterol Hepatol 6: 257-276
MeSH Terms: Animals, Bone Morphogenetic Protein 2, Carcinoma, Cell Line, Cell Line, Tumor, Colitis, Colorectal Neoplasms, Dextran Sulfate, Humans, Inflammation, Intestinal Mucosa, Mice, Mice, Inbred C57BL, Mice, Transgenic, Smad4 Protein, Transforming Growth Factor beta1
Show Abstract · Added September 12, 2018
Background & Aims - Chronic inflammation is a predisposing condition for colorectal cancer. Many studies to date have focused on proinflammatory signaling pathways in the colon. Understanding the mechanisms that suppress inflammation, particularly in epithelial cells, is critical for developing therapeutic interventions. Here, we explored the roles of transforming growth factor β (TGFβ) family signaling through SMAD4 in colonic epithelial cells.
Methods - The gene was deleted specifically in adult murine intestinal epithelium. Colitis was induced by 3 rounds of dextran sodium sulfate in drinking water, after which mice were observed for up to 3 months. Nontransformed mouse colonocyte cell lines and colonoid cultures and human colorectal cancer cell lines were analyzed for responses to TGFβ1 and bone morphogenetic protein 2.
Results - Dextran sodium sulfate treatment was sufficient to drive carcinogenesis in mice lacking colonic expression, with resulting tumors bearing striking resemblance to human colitis-associated carcinoma. Loss of SMAD4 protein was observed in 48% of human colitis-associated carcinoma samples as compared with 19% of sporadic colorectal carcinomas. Loss of increased the expression of inflammatory mediators within nontransformed mouse colon epithelial cells in vivo. In vitro analysis of mouse and human colonic epithelial cell lines and organoids indicated that much of this regulation was cell autonomous. Furthermore, TGFβ signaling inhibited the epithelial inflammatory response to proinflammatory cytokines.
Conclusions - TGFβ suppresses the expression of proinflammatory genes in the colon epithelium, and loss of its downstream mediator, SMAD4, is sufficient to initiate inflammation-driven colon cancer. Transcript profiling: GSE100082.
1 Communities
1 Members
0 Resources
16 MeSH Terms
Antibody Responses to Subspecies Proteins in a Large Prospective Colorectal Cancer Cohort Consortium.
Butt J, Blot WJ, Teras LR, Visvanathan K, Le Marchand L, Haiman CA, Chen Y, Bao Y, Sesso HD, Wassertheil-Smoller S, Ho GY, Tinker LF, Peek RM, Potter JD, Cover TL, Hendrix LH, Huang LC, Waterboer T, Pawlita M, Epplein M
(2018) Cancer Epidemiol Biomarkers Prev 27: 1186-1194
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Bacterial, Antibody Formation, Bacterial Proteins, Case-Control Studies, Colorectal Neoplasms, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Streptococcal Infections, Streptococcus gallolyticus subspecies gallolyticus, Young Adult
Show Abstract · Added July 29, 2018
Antibody responses to subspecies (SGG) proteins, especially pilus protein Gallo2178, have been consistently associated with colorectal cancer risk. Previous case-control studies and prospective studies with up to 8 years of follow-up, however, were unable to decipher the temporality of antibody responses to SGG in the context of the long-term multistep development of colorectal cancer. In this study, we analyzed a large U.S. colorectal cancer cohort consortium with follow-up beyond 10 years for antibody responses to SGG. We applied multiplex serology to measure antibody responses to 9 SGG proteins in participants of 10 prospective U.S. cohorts (CLUE, CPSII, HPFS, MEC, NHS, NYUWHS, PHS, PLCO, SCCS, and WHI) including 4,063 incident colorectal cancer cases and 4,063 matched controls. Conditional logistic regression was used to assess whether antibody responses to SGG were associated with colorectal cancer risk, overall and by time between blood draw and diagnosis. Colorectal cancer risk was increased among those with antibody responses to Gallo2178, albeit not statistically significant [OR, 1.23; 95% confidence interval (CI), 0.99-1.52]. This association was stronger for cases diagnosed <10 years after blood draw (OR, 1.40; 95% CI, 1.09-1.79), but was not found among cases diagnosed ≥10 years after blood draw (OR, 0.79; 95% CI, 0.50-1.24). In a large cohort consortium, we reproduced the association of antibody responses to SGG Gallo2178 with colorectal cancer risk for individuals diagnosed within 10 years after blood draw. This timing-specific finding suggests that antibody responses to SGG are associated with increased colorectal cancer risk only after tumorigenesis has begun. .
©2018 American Association for Cancer Research.
0 Communities
1 Members
0 Resources
19 MeSH Terms