scholarly journals Winnie-APCMin/+ Mice: A Spontaneous Model of Colitis-Associated Colorectal Cancer Combining Genetics and Inflammation

2020 ◽  
Vol 21 (8) ◽  
pp. 2972
Author(s):  
Stefania De Santis ◽  
Giulio Verna ◽  
Grazia Serino ◽  
Raffaele Armentano ◽  
Elisabetta Cavalcanti ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Distal Colon ◽  
Molecular Signature ◽  
Low Grade ◽  
Perfect Model ◽  
Mucin 2 ◽  
Small Intestinal ◽  
The Relationship ◽  
Early Occurrence

(1) Background: Colorectal cancer (CRC) is among the best examples of the relationship between inflammation and increased cancer risk. (2) Methods: To examine the effects of spontaneous low-grade chronic inflammation on the pathogenesis of CRC, we developed a new murine model of colitis-associated cancer (CAC) by crossing Mucin 2 mutated mice (Winnie) with ApcMin/+ mice. (3) Results: The resulting Winnie-ApcMin/+ model combines an inflammatory background with a genetic predisposition to small intestinal polyposis. Winnie-ApcMin/+ mice show an early occurrence of inflammatory signs and dysplastic lesions in the distal colon with a specific molecular signature. (4) Conclusion: The Winnie-ApcMin/+ model is a perfect model to demonstrate that chronic inflammation represents a crucial risk factor for the onset and progression of tumoral lesions in individuals genetically predisposed to CRC.

scholarly journals NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer Development

2018 ◽  
Vol 9 ◽  
Author(s):  
Patricia Ahechu ◽  
Gabriel Zozaya ◽  
Pablo Martí ◽  
José Luis Hernández-Lizoáin ◽  
Jorge Baixauli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Nlrp3 Inflammasome ◽  
Cancer Development ◽  
Low Grade

Circulating Fibrinogen to Pre-albumin Ratio for Chemotherapy Efficacy Prediction and Prognosis of Colorectal Cancer Patients

2020 ◽  
Author(s):  
Hou-Qun Ying ◽  
Fan Sun ◽  
Wei Wang ◽  
Dan Cai ◽  
Ying Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Chronic Inflammation ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Independent Prognostic Factor ◽  
Low Grade ◽  
Albumin Ratio ◽  
Response To Chemotherapy ◽  
Chemotherapy Efficacy

Abstract Background Evaluating chronic inflammation in colorectal cancer (CRC) may aid in identifying patients at the highest risk of recurrence or progression, and help inform clinical treatment decisions. Here, we report the effect of fibrinogen to pre-albumin ratio (FPR) in determining response to chemotherapy and reveal outcomes in CRC patients. Methods A total of 2917 eligible CRC patients from multiple-centers were enrolled, and the outcome of these patients was obtained by three years’ follow-up. Circulating fibrinogen, albumin, pre-albumin, CEA, CA199 and FPR were detected and calculated in these patients. Kaplan-Meier curves, Cox regression, time-dependent ROC, Harrell’s concordance index, calibration and decision curves were used to investigate the role of FPR in clinical outcome of CRC patients. Results Our results reveal significantly inferior outcomes in right- than left-sided patients with advanced CRC (stage III and IV), with preoperative FPR found to be a robust and independent prognostic factor for CRC at each stage. Moreover, prognostic nomograms, including FPR, effectively predicted clinical outcomes of the patients. Furthermore, preoperative FPR was significantly associated with chemotherapy efficacy. Specifically, low-grade (FPR < 15) and medium-grade (15 ≤ FPR < 20) FPR patients exhibited complete response to chemotherapy and attenuated chemosensitivity, respectively, whereas high-grade inflammation (FPR ≥ 20) conferred resistance to the treatment. Conclusion CRC-related inflammation affects response to chemotherapy and the resultant clinical outcomes. Circulating FPR is a simple, economically-friendly and robust independent prognostic factor for effectively predicting outcomes of CRC patients. Targeting chronic inflammation and its corresponding signaling pathway, coupled with measuring FPR, presents a novel approach for clinical management of CRC.

Protagonist of Immuno-Profiling, Immuno-Scoring, and Immunotherapy Towards Colitis-Associated Cancer

2021 ◽  
pp. 24-37
Author(s):  
Mohamed Adil ◽  
Anandraj K. Vaithy.k ◽  
Ashok Kumar Pandurangan ◽  
Mohammad Waseem ◽  
Neesar Ahmed
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Radiation Therapy ◽  
Targeted Therapy ◽  
Chronic Inflammation ◽  
Hormonal Therapy ◽  
Associated Factors ◽  
Intestinal Epithelial ◽  
Increased Risk ◽  
The Relationship

Chronic inflammation in the large intestinal epithelial to rectum is a major risk for malignancies. The pathogenesis of colitis associated cancer is distinct with perilous molecular mechanism. The inflammation leads to damage of cells resulting in symptomatic conditions including cancer. This suggest the relationship between certain cancer due to its associated factors such as environment, genetics, and chronic inflammation leading to cancer. Colorectal cancer (CRC) has also been acknowledged as bowel, rectal, or colon cancer. The most common types of adenocarcinomas are associated with colorectal cancer. The lymphomas, carcinoids, sarcoma, and gastrointestinal tumors are also associated with CRC. Most disorders with chronic inflammation and exposure of immunosuppressant have an increased risk with the development of cancer leading towards the treatment of cancer by various therapies like radiation therapy, chemotherapy, hormonal therapy, further into immunotherapy, and targeted therapy. The prognosis of CRC has always been controversial.

Diabetes associated with abnormal p53 immunohistochemical patterns in colorectal cancer

2020 ◽  
Author(s):  
Zeran Yang ◽  
Jie Ma ◽  
Guangwei Qi ◽  
Xin Zhang
Keyword(s):  
Colorectal Cancer ◽  
P53 Protein ◽  
Distal Colon ◽  
Tp53 Gene ◽  
Proximal Colon ◽  
P53 Expression ◽  
Node Metastasis ◽  
Abnormal Pattern ◽  
The Relationship

Abstract Background Previous study has suggested a link between diabetes and colorectal cancer (CRC), but the specific molecule for the link has not been well-understood. Abnormal p53 immunohistochemical (IHC) pattern is an accurate predictor for TP53 gene mutation. The present study aimed to investigate the relationship between type 2 diabetes mellitus (T2DM) and p53 IHC patterns in CRC. Methods We analyzed p53 protein expression of 742 cases of CRC with radical colectomy by immunohistochemistry. The patients were grouped into subsets of non-diabetes (n = 570) and diabetes (n = 172), and further divided into subgroups of 1 normal p53 IHC pattern (p53 wild type or WT) and 3 abnormal p53 IHC patterns which included heterogeneous pattern (HT), overexpression (OE) and complete absence (CA). Results The ratios of p53 abnormal pattern in groups of T2DM and non-T2DM were 70.9% and 50.9% (P < 0.001). Univariately, groups of both T2DM and prediabetes (FPG: 6.1 ~ 6.9 mmol/L) were significantly associated with abnormal p53 pattern, compared with normal FPG control (P < 0.05 and P < 0.001). Moreover, T2DM was significantly associated with abnormal p53 patterns in cases with microsatellite instability (MSI) stable (MSS)/MSI-low phenotype (P < 0.001) and distal colon/rectum location, but not in cases with MSI-high phenotype and proximal colon location (P > 0.05). Multivariate analysis retained the above significance. Furthermore, abnormal p53 IHC patterns were positively associated with risk of lymph node metastasis and high tumor-node-metastasis (TNM) stage of CRC, which suggested a link between the abnormal p53 IHC patterns and aggressive clinical outcome. Conclusion Diabetes is associated with risk of abnormal p53 IHC patterns in CRC. It was suggested that diabetes might influence carcinogenesis, progression and prognosis via inducing TP53 mutation and abnormal p53 expression in CRC.

CD133/CD166/Ki-67 Triple Immunouorescence Assessment for Putative Cancer Stem Cells in Colon Carcinoma*

2014 ◽  
Vol 23 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Claudiu Margaritescu ◽  
Daniel Pirici ◽  
Irina Cherciu ◽  
Alexandru Barbalan ◽  
Tatiana Cârtâna ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Stem Cells ◽  
Colon Carcinoma ◽  
Sodium Dodecyl ◽  
High Grade Dysplasia ◽  
Early Event ◽  
Low Grade ◽  
High Grade

Background & Aims: Colorectal cancer represents the third most common malignancy and the fourth most common cause of cancer death worldwide. The existence of drug-resistant colon cancer stem cells is thought to be one of the most important reasons behind treatment failure in colon cancer, their existence putatively leading to metastasis and recurrences. The aim of our study was to investigate the immunoexpression patterns of CD133 and CD166 in colon carcinoma, both individually and in combination, assessing their significance as prognostic markers.Methods. A total of 45 retrospective colon adenocarcinoma cases were investigated by enzymatic and multiple fluorescence immunohistochemistry for their CD133 and CD166 expression and colocalization.Results. Both CD133 and CD166 were expressed to different extents in all cancer specimens, with apredominant cytoplasmic pattern for CD133 and a more obvious membranous-like pattern for CD166.Overall, when comparing their reactivity for the tumoral tissue, CD166 expression areas seemed to be smaller than those of CD133. However, there was a direct correlation between CD133 and CD166 expression levels throughout the entire spectrum of lesions, with higher values for dysplastic lesions. Colocalization of CD133/ CD166 was obvious at the level of cells membranes, with higher coeficients in high grade dysplasia, followed by well and moderate differentiated tumours.Conclusions. CD133/CD166 colocalization is an early event occurring in colon tumorigenesis, with thehighest coeficients recorded for patients with high grade dysplasia, followed by well differentiated tumours. Thus, we consider that the coexpression of these two markers could be useful for further prognostic andtherapeutically stratification of patients with colon cancer.Abbreviations: AJCC - American Joint Committee on Cancer; CCD - charge-coupled device camera sensor; CD133 - prominin-1 (PROM1); CD166 - Activated Leukocyte Cell Adhesion Molecule (ALCAM); CRC - colorectal cancer; CSC - cancer stem cells; DAB - 3,3'-diaminobenzidine chromogen; DAPI - 4',6-diamidino- 2-phenylindole; HE - Hematoxylin and eosin staining; HGD - high grade dysplasia; HRP - horseradish peroxidase; LGD - low grade dysplasia; SDS - sodium dodecyl sulfate*Part of this work has been accepted as a poster presentation at the Digestive Disease Week (DDW) meeting, Chicago, IL, USA May 3-6, 2014

Role of inflammation in the development of colorectal cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
R. Ileng Kumaran ◽  
Kokelavani Nampalli Babu ◽  
Sneha Krishnamoorthy ◽  
Akash Guruswamy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Interleukin 1 ◽  
Cell Types ◽  
Model Systems ◽  
Cytokine Gene Expression ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

Primary acquired melanosis (PAM) without atypia/WHO low-grade conjunctival melanocytic intraepithelial lesion over areas of oculodermal melanocytosis

2020 ◽  
Vol 13 (10) ◽  
pp. e236741
Author(s):  
Bashar M Bata ◽  
Sachin M Salvi ◽  
Hardeep Singh Mudhar
Keyword(s):  
Bulbar Conjunctiva ◽  
Low Grade ◽  
Primary Acquired Melanosis ◽  
Conjunctival Biopsy ◽  
History Of ◽  
Intraepithelial Lesion ◽  
The Relationship ◽  
Oculodermal Melanocytosis ◽  
Substantia Propria ◽  
New Onset

An elderly white man with a history of left oculodermal melanocytosis presented with new onset brown pigmentation of the left bulbar and inferior tarsal conjunctiva. The bulbar conjunctival pigmentation was at the level of the conjunctival epithelium and was overlying areas of typical slate-grey scleral pigmentation characteristic of oculodermal melanocytosis. Both areas of new pigmentation were biopsied. The bulbar conjunctiva revealed primary acquired melanosis (PAM) without atypia with increased melanin production and the tarsal conjunctival biopsy showed PAM without atypia sine pigmentio overlying areas of substantia propria spindle-shaped heavily pigmented melanocytes of oculodermal melanocytosis. The case report examines the relationship between the epithelial and substantia propria melanocytes and correlates the findings with what is known about this association from the dermatopathology literature.

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