scholarly journals Monocyte Chemotactic Proteins (MCP) in Colorectal Adenomas Are Differently Expressed at the Transcriptional and Protein Levels: Implications for Colorectal Cancer Prevention

2021 ◽  
Vol 10 (23) ◽  
pp. 5559
Author(s):  
Jarosław Wierzbicki ◽  
Artur Lipiński ◽  
Iwona Bednarz-Misa ◽  
Łukasz Lewandowski ◽  
Katarzyna Neubauer ◽  
...  

The expression of monocyte chemotactic proteins (MCPs) in colorectal polyps and their suitability as targets for chemoprevention is unknown, although MCP expression and secretion can be modulated by non-steroidal inflammatory drugs. This study was designed to determine the expression patterns of MCP-1/CCL2, MCP-2/CCL8, and MCP-3/CCL7 at the protein (immunohistochemistry; n = 62) and transcriptional levels (RTqPCR; n = 173) in colorectal polyps with reference to the polyp malignancy potential. All chemokines were significantly upregulated in polyps at the protein level but downregulated at the transcriptional level by 1.4-(CCL2), 1.7-(CCL7), and 2.3-fold (CCL8). There was an inverse relation between the immunoreactivity toward chemokine proteins and the number of corresponding transcripts in polyps (CCL2 and CCL7) or in normal mucosa (CCL8). The downregulation of chemokine transcripts correlated with the presence of multiple polyps (CCL2 and CCL8), a larger polyp size (CCL2, CCL7, and CCL8), predominant villous growth patterns (CCL2, CCL7 and CCL8), and high-grade dysplasia (CCL2 and CCL8). In conclusion, MCP-1/CCL2, MCP-2/CCL8, and MCP-3/CCL7 chemokines are counter-regulated at the protein and transcriptional levels. Chemokine-directed chemopreventive strategies should therefore directly neutralize MCP proteins or target molecular pathways contributing to their enhanced translation or reduced degradation, rather than aiming at CCL2, CCL7 or CCL8 expression.

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Nina Hauptman ◽  
Emanuela Boštjančič ◽  
Margareta Žlajpah ◽  
Branislava Ranković ◽  
Nina Zidar

Colorectal cancer (CRC) is one of the leading causes of death by cancer worldwide. Bowel cancer screening programs enable us to detect early lesions and improve the prognosis of patients with CRC. However, they also generate a significant number of problematic polyps, e.g., adenomas with epithelial misplacement (pseudoinvasion) which can mimic early adenocarcinoma. Therefore, biomarkers that would enable us to distinguish between adenoma with epithelial misplacement (pseudoinvasion) and adenoma with early adenocarcinomas (true invasion) are needed. We hypothesized that the former are genetically similar to adenoma and the latter to adenocarcinoma and we used bioinformatics approach to search for candidate genes that might be potentially used to distinguish between the two lesions. We used publicly available data from Gene Expression Omnibus database and we analyzed gene expression profiles of 252 samples of normal mucosa, colorectal adenoma, and carcinoma. In total, we analyzed 122 colorectal adenomas, 59 colorectal carcinomas, and 62 normal mucosa samples. We have identified 16 genes with differential expression in carcinoma compared to adenoma:COL12A1,COL1A2,COL3A1, DCN, PLAU, SPARC, SPON2, SPP1,SULF1,FADS1, G0S2, EPHA4, KIAA1324,L1TD1, PCKS1, andC11orf96. In conclusion, ourin silicoanalysis revealed 16 candidate genes with different expression patterns in adenoma compared to carcinoma, which might be used to discriminate between these two lesions.


2021 ◽  
Vol 09 (05) ◽  
pp. E706-E712
Author(s):  
Rayan Saade ◽  
Tyler Tsang ◽  
Michel Kmeid ◽  
David Miller ◽  
Zhiyan Fu ◽  
...  

Abstract Background and study aims Adequate removal of precancerous polyps is an independent factor in colorectal cancer prevention. Despite advances in polypectomy techniques, there is an increasing rate of surgery for benign polyps. We assessed whether surgical resection is properly utilized for benign colorectal polyps. Patients and methods We identified 144 patients with surgical resection for benign colorectal polyps. Polyp location, size and the indication for and type of surgery were obtained. For the purposes of this analysis, we assumed that gastroenterologists should assess polyp size accurately, endoscopically resect polyps < 2 cm, and treat incompletely excised polyps on follow-up. Results A total of 118 patients (82 %) were referred to surgery without attempted endoscopic removal. In 26 (22 %) of 118, the macroscopic polyp size was < 2 cm (23 in right, 3 in the left colon) and 18 (15 %; 14 in the right, four in the left colon) were found to have had size overestimation during endoscopy. Twenty-two (15 %) of 144 underwent surgical resection for incomplete endoscopic resection of adenomas (16 in the right, 6 in the left colon); 12 (54.5 %) had a residual polyp size of < 2 cm (10 in the right colon; 2 in the left colon). In-hospital mortality was 0.7 % and morbidity was 20.1 %. Conclusions Of the patients, 41 % could have potentially avoided surgical intervention (37 polyps < 2 cm and/or size overestimations precluding endoscopic polypectomy and 22 incomplete resections). When including polyps with size ≥ 2 to < 4 cm, the percentage of patients with avoidable surgery reached 80 %. This confirms the need to develop standardized quality metrics for endoscopic polypectomies and for better overall training of endoscopists performing these procedures. Given the risks of surgery, referral to an experienced gastroenterologist should be considered as a first step.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 549-549
Author(s):  
Kyoung-Joo Kwon ◽  
Ki-Nam Shim ◽  
Sung-Ae Jung ◽  
Hye-Kyung Jung ◽  
Seong-Eun Kim ◽  
...  

549 Background: Gastric polyps are found frequently in various colonic polyposis syndromes. Genetic alterations of several genes occur in gastric adenomas and colorectal adenomas. However, it is unknown whether patients with gastric cancers are at higher risk for colorectal adenomas. Methods: We retrospectively reviewed the medical records in 112 patients with gastric cancers from January 2005 to December 2009. Patients who were diagnosed with gastric cancers and had colonoscopy within 6 months were compared to 220 sex and age-matched controls from 3,725 persons who underwent esophagogastroduodenoscopy and colonoscopy for screening at the Center for Health Promotion in Ewha Womans University Medical Center. High risk polyp was defined by any of the following: (1) the presence of three or more polyps; (2) polyp size at least 10mm; (3) high-grade dysplasia or adenocarcinoma confirmed by histopathologic examination. Otherwise the polyps were defined as low risk. Results: Mean age was 59 years-old and 70% was male in patients with gastric cancer. Overweight (BMI ≥ 23) was more common in control group (gastric cancer versus control: 56% and 69%, respectively, P = 0.025). Colorectal polyps were identified in 67 of 112 patients (59.8%) with gastric cancer and in 153 of 220 controls (69.5%). The prevalence of high risk polyps were numerically higher in the gastric cancer group than the control group, although not statistically significant (9% vs. 4%, P = 0.267). In contrast, the prevalence of low risk polyps were significantly frequent in the control group (91% vs. 96%, P = 0.024). The mean size and number of colorectal polyps were not different between the two groups. Adenocarcinoma was diagnosed from polyps in five patients (7%) with gastric cancer and four patients (2%) with control group (P = 0.190). Conclusions: The overall colorectal polyps, especially low risk polyps, were more prevalent in the control group. In contrast, high risk polyps and adenocarcinoma is more frequently found in patients with gastric cancer although not significant. Therefore, we suggest that colorectal polyps should be cautiously examined in patients with gastric cancer.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Franziska Eberl ◽  
Thomas Fabisch ◽  
Katrin Luck ◽  
Tobias G. Köllner ◽  
Heiko Vogel ◽  
...  

Abstract Background Protease inhibitors are defense proteins widely distributed in the plant kingdom. By reducing the activity of digestive enzymes in insect guts, they reduce the availability of nutrients and thus impair the growth and development of the attacking herbivore. One well-characterized class of protease inhibitors are Kunitz-type trypsin inhibitors (KTIs), which have been described in various plant species, including Populus spp. Long-lived woody perennials like poplar trees encounter a huge diversity of herbivores, but the specificity of tree defenses towards different herbivore species is hardly studied. We therefore aimed to investigate the induction of KTIs in black poplar (P. nigra) leaves upon herbivory by three different chewing herbivores, Lymantria dispar and Amata mogadorensis caterpillars, and Phratora vulgatissima beetles. Results We identified and generated full-length cDNA sequences of 17 KTIs that are upregulated upon herbivory in black poplar leaves, and analyzed the expression patterns of the eight most up-regulated KTIs via qRT-PCR. We found that beetles elicited higher transcriptional induction of KTIs than caterpillars, and that both caterpillar species induced similar KTI expression levels. Furthermore, KTI expression strongly correlated with the trypsin-inhibiting activity in the herbivore-damaged leaves, but was not dependent on damage severity, i.e. leaf area loss, for most of the genes. Conclusions We conclude that the induction of KTIs in black poplar is controlled at the transcriptional level in a threshold-based manner and is strongly influenced by the species identity of the herbivore. However, the underlying molecular mechanisms and ecological consequences of these patterns remain to be investigated.


2008 ◽  
Vol 100 (4) ◽  
pp. 2015-2025 ◽  
Author(s):  
Julie E. Miller ◽  
Elizabeth Spiteri ◽  
Michael C. Condro ◽  
Ryan T. Dosumu-Johnson ◽  
Daniel H. Geschwind ◽  
...  

Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.


Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 218
Author(s):  
Amalie Scheel Tost ◽  
Astrid Kristensen ◽  
Lene Irene Olsen ◽  
Kristian Buhl Axelsen ◽  
Anja Thoe Fuglsang

Small post-translationally modified peptides are gaining increasing attention as important signaling molecules in plant development. In the family of plant peptides containing tyrosine sulfation (PSYs), only PSY1 has been characterized at the mature level as an 18-amino-acid peptide, carrying one sulfated tyrosine, and involved in cell elongation. This review presents seven additional homologs in Arabidopsis all sharing high conservation in the active peptide domain, and it shows that PSY peptides are found in all higher plants and mosses. It is proposed that all eight PSY homologs are post-translationally modified to carry a sulfated tyrosine and that subtilisin-like subtilases (SBTs) are involved in the processing of PSY propeptides. The PSY peptides show differential expression patterns indicating that they serve several distinct functions in plant development. PSY peptides seem to be at least partly regulated at the transcriptional level, as their expression is greatly influenced by developmental factors. Finally, a model including a receptor in addition to PSY1R is proposed.


Biologia ◽  
2014 ◽  
Vol 69 (12) ◽  
Author(s):  
Keum Jeong ◽  
Jae-Hong Pak ◽  
Jeong Kim

AbstractGalium L. is one of the largest and most widespread genus of Rubiaceae, consisting of more than 650 species worldwide. Galium verum var. asiaticum (G. verum a.) is a perennial herbaceous and widely distributed in in Korea peninsula. On the other hand, Galium verum var. asiaticum for. pusillum (G. verum a.p.) is endemic to Korea, inhabiting only on high land of Mt. Halla of Jeju. G. verum a.p. appears to be a dwarfism of G. verum a. We wondered what physiological, environmental, or genetic factors rendered those two taxa morphologically differentiated. We found that G. verum a.p. shows a low activity of the cell proliferation and was not associated with responsiveness contents of auxin and gibberellins. In order to search for genetic factors involved, we carried out an mRNA differential display method using the ACPs, and isolated several different expression genes between the two taxa. We chose one of those genes, which encoded RADIALIS-like proteins: GvaRADL1 from G. verum a. and GvapRADL1 from G. verum a.p. We discuss the relevancy of the genetic variations in regard to the differential expression patterns of those genes and the differential growth patterns of the two variants.


2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 98-99
Author(s):  
M Taghiakbari ◽  
R Djinbachian ◽  
D von Renteln

Abstract Background Optical polyp diagnosis can be used for real-time pathology prediction of colorectal polyps ≤10 mm. However, the risk of misdiagnosing a polyp with advanced pathology potentially increases with increasing polyp size. Aims This study aimed to evaluate different size cut-offs for using optical polyp diagnosis and the associated risk of patients undergoing inadequate follow-up or surveillance. Methods In a post-hoc analysis of two prospective studies, the performance of optical diagnosis was evaluated in three polyp size groups: 1–3 mm, 1–5 mm, and 1–10 mm. The primary outcome was the proportion of patients with advanced adenomas and delayed or inappropriate surveillance. Secondary outcomes included percentage of polyps with advanced pathology, agreement between surveillance intervals based on high-confidence optical diagnosis and pathology outcomes, reduction in histopathological examinations, and proportion of patients who could receive an immediate surveillance interval recommendation. Results We included 1525 patients with complete colonoscopies (mean age 62.9 years, 50.2% male). The percentage of patients with advanced adenomas and delayed or inappropriate surveillance was 0.7%, 1.7%, and 1.8% when using optical diagnosis for patients with polyps of 1–3, 1–5, and 1–10 mm, respectively. The percentage of polyps with advanced pathology was 0.5%, 1.4%, and 1.9%, respectively. Surveillance interval agreement between pathology and optical diagnosis was 99%, 98%, and 97.8%, respectively. Total reduction in pathology examinations was 33.9%, 53.5%, and 69.0%, respectively. Conclusions A 3-mm cut-off for clinical implementation of optical polyp diagnosis yielded high surveillance interval agreement with pathology and a high reduction in pathology examinations while minimizing the risk of inappropriate management for polyps with advanced pathology. Funding Agencies None


2011 ◽  
Vol 205 (2) ◽  
pp. 132.e1-132.e12 ◽  
Author(s):  
Gesina D.S. Ernst ◽  
Layla L. de Jonge ◽  
Albert Hofman ◽  
Jan Lindemans ◽  
Henk Russcher ◽  
...  

Author(s):  
Silvana Marques e SILVA ◽  
Viviane Fernandes ROSA ◽  
Antônio Carlos Nóbrega dos SANTOS ◽  
Romulo Medeiros de ALMEIDA ◽  
Paulo Gonçalves de OLIVEIRA ◽  
...  

BACKGROUND: Colorectal cancer is a major cause of morbidity and mortality and can arise through the adenoma-carcinoma sequence. Colonoscopy is considered the method of choice for population-wide cancer screening. AIM: To assess the characteristics of endoscopically resected polyps in a consecutive series of patients who underwent colonoscopy at a university hospital and compare histopathology findings according to patient age and polyp size. METHODS: Retrospective, cross-sectional of 1950 colonoscopy reports from consecutively examined patients. The sample was restricted to reports that mentioned colorectal polyps. A chart review was carried out for collection of demographic data and histopathology results. Data were compared for polyps sized ≤0.5 cm and ≥0.6 cm and then for polyps sized ≤1.0 cm and ≥1.1 cm. Finally, all polyps resected from patients aged 49 years or younger were compared with those resected from patients aged 50 years or older. RESULTS: A total of 272 colorectal polyps were resected in 224 of the 1950 colonoscopies included in the sample (11.5%). Polyps >1 cm tended to be pedunculated (p=0.000) and were more likely to exhibit an adenomatous component (p=0.001), a villous component (p=0.000), and dysplasia (p=0.003). These findings held true when the size cutoff was set at 0.5 cm. Patients aged 50 years or older were more likely to have sessile polyps (p=0.023) and polyps located in the proximal colon (p=0.009). There were no significant differences between groups in histopathology or presence of dysplasia. CONCLUSION: Polyp size is associated with presence of adenomas, a villous component, and dysplasia, whereas patient age is more frequently associated with sessile polyps in the proximal colon.


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