IU Indianapolis ScholarWorks :: Browsing by Subject "colon cancer"

Browsing by Subject "colon cancer"

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Artificial Intelligence Improves Detection at Colonoscopy: Why aren’t we all already using it?
(ScienceDirect, 2022) Rex, Douglas K.; Berzin, Tyler M.; Mori, Yuichi; Medicine, School of Medicine
Critical role of phosphorylation of serine 165 of YBX1 on the activation of NF- B in colon cancer
(Office of the Vice Chancellor for Research, 2015-04-17) Prabhu, Lakshmi; Mundade, Rasika; Wang, Benlian; Wei, Han; Hartley, Antja-Voy; McElyea, Kyle; Temm, Constance J.; Sandusky, George; Liu, Yunlong; Lu, Tao
Y-box binding protein 1 (YBX1) is a multifunctional protein known to facilitate many of the hallmarks of cancer. Elevated levels of YBX1 protein are highly correlated with cancer progression, making it an excellent marker in cancer. The connection between YBX1 and the important nuclear factor B (NF-B), has never been previously reported. Here, we show that overexpression of wild type YBX1 (wtYBX1) activates NF-B, suggesting that YBX1 is a potential NF-B activator. Furthermore, using mass spectrometry analysis, we identified novel phosphorylation of serine 165 (S165) on YBX1. Overexpression of the S165A-YBX1 mutant in either 293 cells or colon cancer HT29 cells showed dramatically reduced NF-B activating ability as compared to that of wtYBX1, confirming that S165 phosphorylation is critical for the activation of NF-B by YBX1. We further show that expression of the S165A-YBX1 mutant dramatically decreased the expression of NF-B-inducible genes, reduced cell growth, and compromised tumorigenic ability as compared to wtYBX1. Taken together, we provide the first evidence that YBX1 functions as a tumor promoter via NF-B activation, and phosphorylation of S165 of YBX1 is critical for this function. Therefore, our important discovery may lead to blocking S165 phosphorylation as a potential therapeutic strategy to treat colon cancer.
Critical role of phosphorylation of serine 165 of YBX1 on the activation of NF-κB in colon cancer.
(Impact Journals, 2015-10-06) Prabhu, Lakshmi; Mundade, Rasika; Wang, Benlian; Wei, Han; Hartley, Antja-Voy; Martin, Matthew; McElyea, Kyle; Temm, Constance J.; Sandusky, George; Liu, Yunlong; Lu, Tao; Department of Pharmacology and Toxicology, IU School of Medicine
Y-box binding protein 1 [YBX1] is a multifunctional protein known to facilitate many of the hallmarks of cancer. Elevated levels of YBX1 protein are highly correlated with cancer progression, making it an excellent marker in cancer. The connection between YBX1 and the important nuclear factor κB [NF-κB] has never been reported. Here, we show that overexpression of wild type YBX1 [WT-YBX1] activates NF-κB, suggesting that YBX1 is a potential NF-κB activator. Furthermore, using mass spectrometry analysis we identified novel phosphorylation of serine 165 [S165] on YBX1. Overexpression of the S165A-YBX1 mutant in either HEK293 cells or colon cancer HT29 cells showed dramatically reduced NF-κB activating ability as compared with that of WT-YBX1, confirming that S165 phosphorylation is critical for the activation of NF-κB by YBX1. We also show that expression of the S165A-YBX1 mutant dramatically decreased the expression of
DNA methyltransferase inhibition reduces inflammation-induced colon tumorigenesis
(Taylor & Francis, 2019-06-26) Maiuri, Ashley R.; Savant, Sudha S.; Podicheti, Ram; Rusch, Douglas B.; O’Hagan, Heather M.; Medical and Molecular Genetics, School of Medicine
Chronic inflammation is strongly associated with an increased risk of developing colorectal cancer. DNA hypermethylation of CpG islands alters the expression of genes in cancer cells and plays an important role in carcinogenesis. Chronic inflammation is also associated with DNA methylation alterations and in a mouse model of inflammation-induced colon tumorigenesis, we previously demonstrated that inflammation-induced tumours have 203 unique regions with DNA hypermethylation compared to uninflamed epithelium. To determine if altering inflammation-induced DNA hypermethylation reduces tumorigenesis, we used the same mouse model and treated mice with the DNA methyltransferase (DNMT) inhibitor decitabine (DAC) throughout the tumorigenesis time frame. DAC treatment caused a significant reduction in colon tumorigenesis. The tumours that did form after DAC treatment had reduced inflammation-specific DNA hypermethylation and alteration of expression of associated candidate genes. When compared, inflammation-induced tumours from control (PBS-treated) mice were enriched for cell proliferation associated gene expression pathways whereas inflammation-induced tumours from DAC-treated mice were enriched for interferon gene signatures. To further understand the altered tumorigenesis, we derived tumoroids from the different tumour types. Interestingly, tumoroids derived from inflammation-induced tumours from control mice maintained many of the inflammation-induced DNA hypermethylation alterations and had higher levels of DNA hypermethylation at these regions than tumoroids from DAC-treated mice. Importantly, tumoroids derived from inflammation-induced tumours from the DAC-treated mice proliferated more slowly than those derived from the inflammation-induced tumours from control mice. These studies suggest that inhibition of inflammation-induced DNA hypermethylation may be an effective strategy to reduce inflammation-induced tumorigenesis.
Endocuff Vision Reduces Inspection Time Without Decreasing Lesion Detection in a Randomized Colonoscopy Trial
(Elsevier, 2019) Rex, Douglas K.; Slaven, James E.; Garcia, Jonathan; Lahr, Rachel; Searight, Meghan; Gross, Seth A.; Medicine, School of Medicine
Background & Aims Mucosal exposure devices improve detection of lesions during colonoscopy and have reduced examination times in uncontrolled studies. We performed a randomized trial of Endocuff Vision vs standard colonoscopy to compare differences in withdrawal time (the primary end point). We proposed that Endocuff Vision would allow complete mucosal inspection in a shorter time without impairing lesion detection. Methods Adults older than 40 years undergoing screening or surveillance colonoscopies were randomly assigned to the Endocuff group (n=101, 43.6% women) or the standard colonoscopy group (n=99; 57.6% women). One of 2 experienced endoscopists performed the colonoscopies, aiming for a thorough evaluation of the proximal sides of all haustral folds, flexures, and valves in the shortest time possible. Inspection time was measured with a stopwatch and calculated by subtracting washing, suctioning, polypectomy and biopsy times from total withdrawal time. Results There were significantly fewer women in the Endocuff arm (P = .0475) but there were no other demographic differences between groups. Mean insertion time with Endocuff was 4.0 min vs 4.4 min for standard colonoscopy (P = .14). Mean inspection time with Endocuff was 6.5 min vs 8.4 min for standard colonoscopy (P < .0001). Numbers of adenomas detected per colonoscopy (1.43 vs 1.07; P = .07), adenoma detection rate (61.4% vs 52%; P = .21), number of sessile serrated polyps per colonoscopy (0.27 vs 0.21; P = .12), and sessile serrated polyp detection rate (19.8% vs 11.1%; P = .09) were all higher with Endocuff Vision. Results did not differ significantly when we controlled for age, sex, or race. Conclusion In a randomized trial, we found inclusion of Endocuff in screening or surveillance colonoscopies to decrease examination time without reducing lesion detection.
Findings in the Distal Colorectum are not associated with Proximal Advanced Serrated Lesions
(Elsevier, 2015-02) Kahi, Charles J.; Vemulapalli, Krishna C.; Snover, Dale C.; Jawad, Khaled H. Abdel; Cummings, Oscar W.; Rex, Douglas K.; Department of Medicine, IU School of Medicine
Background & Aims Serrated lesions are an important contributor to colorectal cancer (CRC), notably in the proximal colon. Findings in the distal colorectum are markers of advanced proximal adenomatous neoplasia. However, it is not known whether they affect the odds of advanced proximal serrated lesions. Methods We performed a retrospective cross-sectional study of data from 1910 patients (59.3 ± 8.0 years, 53.8% female) who underwent an average-risk screening colonoscopy from August 2005 through April 2012 at Indiana University Hospital and an associated ambulatory surgery center. Colonoscopies were performed by an endoscopist with high rates of detection of adenomas and serrated polyps. Tissue samples of all serrated polyps (hyperplastic, sessile serrated adenoma/polyp [SSA/P], or traditional serrated adenoma) proximal to the sigmoid colon and serrated polyps >5 mm in the rectum or sigmoid colon were reviewed by a gastrointestinal pathologist and reclassified on the basis of World Health Organization criteria. Advanced serrated lesion (ASL) was defined as SSA/P with cytologic dysplasia, SSA/P ≥10 mm, or traditional serrated adenoma. Advanced conventional adenomatous neoplasia (ACN) was defined as tubular adenoma ≥10 mm, villous histology, high-grade dysplasia, or cancer. The prevalence of proximal ASL and ACN was calculated on the basis of distal colorectal findings. Multivariable logistic regression analysis was performed to determine the age-adjusted and sex-adjusted odds of advanced proximal adenomatous and serrated lesions. Secondary analyses were performed to examine the effect of variable ASL definitions. Results Fifty-two patients (2.7%) had proximal ASL, and 99 (5.2%) had proximal ACN. Of the 52 patients with proximal ASL, 27 (52%) had no distal polyps. Of the 99 patients with proximal ACN, 40 (40%) had no distal polyps. Age and type of distal adenomas were significantly associated with proximal ACN. There were no significant associations between distal polyp type and proximal ASL. In secondary analyses, distal SSA/Ps (P = .008) but not distal hyperplastic polyps or conventional adenomas were associated with any proximal SSA/P. Conclusions The findings at flexible sigmoidoscopy that traditionally serve as indications for colonoscopy (conventional adenomas) are likely to be ineffective for detection of proximal ASL. This finding, plus the observation that most patients with proximal ASL have no distal polyps, favors screening colonoscopy over sigmoidoscopy, especially in the elderly. The observation that non-advanced distal SSA/Ps are associated with any proximal SSA/P warrants further study.
Genetic pathways, prevention, and treatment of sporadic colorectal cancer
(Impact Journals, LLC, 2014) Mundade, Rasika; Imperiale, Thomas F.; Prabhu, Lakshmi; Loehrer, Patrick J.; Lu, Tao; Department of Pharmacology and Toxicology, IU School of Medicine
Epithelial cancer of the colon and rectum, also known as colorectal cancer (CRC), results from a progressive accumulation of genetic and epigenetic alterations that lead to uncontrolled growth of colonocytes, the cells lining the colon and rectum. CRC is the second leading cause of cancer-related deaths and the third most common cancer in men and in women in the U.S. Of all the patients diagnosed with CRC every year, it is estimated that the vast majority of CRCs are non-hereditary "sporadic cancers" with no apparent evidence of an inherited component. Sporadic CRC results from the cumulative effects of multiple genetic and epigenetic alterations caused by somatic mutations, which may themselves be the indirect result of several environmental factors. This review examines our current understanding of the major genetic alterations leading to colon cancer, options for prevention and early detection of CRC, and the currently available treatment approaches that may target these different genetic alterations.
How I Approach Retroflexion and Prevention of Right-Sided Colon Cancer Following Colonoscopy
(Nature, 2016) Rex, Douglas K.; Department of Medicine, School of Medicine
New and Recurrent Colorectal Cancers After Resection: a Systematic Review and Meta-analysis of Endoscopic Surveillance Studies
(Elsevier, 2019) Fuccio, Lorenzo; Rex, Douglas K.; Ponchon, Thierry; Frazzoni, Leonardo; Dinis-Ribeiro, Mário; Bhandari, Pradeep; Dekker, Evelien; Pellisè, Maria; Correale, Loredana; van Hooft, Jeanin; Jover, Rodrigo; Libanio, Diogo; Radaelli, Franco; Alfieri, Sergio; Bazzoli, Franco; Senore, Carlo; Regula, Jaroslaw; Seufferlein, Thomas; Rösch, Thomas; Sharma, Prateek; Repici, Alessandro; Hassan, Cesare; Medicine, School of Medicine
Background & Aims Outcomes of endoscopic surveillance following surgery for colorectal cancer (CRC) vary with the incidence and timing of CRC detection, at anastomoses or non- anastomoses in the colorectum. We performed a systematic review and meta-analysis to evaluate the incidence of CRCs identified during surveillance colonoscopies of patients who have already undergone surgery for this cancer. Methods We searched PubMed, EMBASE, SCOPUS, and the Cochrane Central Register of Clinical Trials through January 1, 2018 to identify studies investigating rates of CRCs at anastomoses or other locations in the colorectum after curative surgery for primary CRC. We collected data from published randomized controlled, prospective, and retrospective cohort studies. Data were analyzed by multivariate meta-analytic models. Results From 2373 citations, we selected 27 studies with data on 15,803 index CRCs for analysis (89% of patients with stage 1–3 CRC). Overall, 296 CRCs at non-anastomotic locations were reported over time periods of more than 16 years (cumulative incidence, 2.2% of CRCs; 95% CI, 1.8%–2.9%). The risk of CRC at a non-anastomotic location was significantly reduced more than 36 months after resection compared with before this timepoint (odds ratio for non-anastomotic CRCs at 36–48 months vs 6–12 months after surgery, 0.61; 95% CI, 0.37–0.98; P=.031); 53.7% of all non-anastomotic CRCs were detected within 36 months of surgery. One hundred fifty-eight CRCs were detected at anastomoses (cumulative incidence of 2.7%; 95% CI, 1.9%–3.9%). The risk of CRCs at anastomoses was significantly lower 24 months after resection than before (odds ratio for CRCs at anastomoses at 25–36 months after surgery vs 6–12 months, 0.56; 95% CI, 0.32–0.98; P=.036); 90.8% of all CRCs at anastomoses were detected within 36 months of surgery. Conclusions After surgery for CRC, the highest risk of CRCs at anastomoses and at other locations in the colorectum is highest during 36 months after surgery—risk decreases thereafter. Patients who have undergone CRC resection should be evaluated by colonoscopy more closely during this time period. Longer intervals may be considered thereafter.
Prevalence of Advanced, Precancerous Colorectal Neoplasms in Black and White Populations: A Systematic Review and Meta-analysis
(AGA, 2018) Imperiale, Thomas F.; Abhyankar, Priya R.; Stump, Timothy E.; Emmett, Thomas W.; Medicine, School of Medicine
Background & Aims Colorectal cancer (CRC) incidence and mortality are higher in black vs white populations. The reasons for these disparities are not clear, yet some guidelines recommend screening black persons for CRC starting at ages 40–45 years. We performed a systematic review and meta-analysis to compare the prevalence of advanced adenomas (AAs) and advanced, precancerous colorectal neoplasms (ACNs) between asymptomatic black and white screen-eligible adults. Methods We searched Ovid MEDLINE, PubMed, Embase, and the Cochrane Library to identify articles (published from 1946 through June 2017) that reported prevalence values of AA or ACN in average-risk black and white individuals undergoing screening colonoscopy. Two authors independently assessed study quality and risk for bias using a modified validated quality assessment instrument. Following the PRISMA guidelines, 2 authors independently abstracted descriptive and quantitative data from each study. We performed a random effects meta-analysis to determine risk differences and odds ratios (ORs). Results From 1653 articles, we identified 9 studies for analysis, comprising 302,128 individuals. Six of the 9 studies were of high methodological quality, had a low risk for bias, and were included in the meta-analysis. In these 9 studies, the overall prevalence values for AA and ACN did not differ significantly between back (6.57%) and white screened individuals (6.20%; OR, 1.03; 95% CI, 0.81–1.30). Among a subgroup of 5 studies, the prevalence of proximal AA and ACN was significantly higher in black (3.30%) than in white screened individuals (2.42%; OR, 1.20; 95% CI, 1.12–1.30). Excluding the largest study did not affect overall prevalence (OR, 0.99; CI, 0.73–1.34) but eliminated the difference in prevalence of proximal AA or ACN (OR, 1.48; 95% CI, 0.87–2.52). Conclusions In a meta-analysis, we found the overall prevalence of AA and ACN did not differ significantly between average-risk black and white persons, indicating that the age at which to begin CRC screening need not differ based on race.

Browsing by Subject "colon cancer"

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