Senescent Cells Increase Risk of Colon Cancer via Secretion of GDF15

In this study, we provide both correlative and functional evidence that senescent fibroblasts and an essential SASP factor, GDF15, induce physiological and molecular changes that promote the adenoma-carcinoma initiation and progression sequence in the colon. We assessed the role of senescence and the SASP in CRC formation. Using primary human colon tissue, we found an accumulation of senescent fibroblasts in normal tissues from individuals with advanced adenomas or carcinomas in comparison with individuals with no polyps or CRC. In in vitro and ex vivo model systems, we induced senescence using oxidative stress in colon fibroblasts and demonstrated that the senescent fibroblasts secrete GDF15 as an essential SASP factor that promotes cell proliferation, migration, and invasion in colon adenoma and CRC cell lines as well as primary colon organoids via the MAPK and PI3K signaling pathways. In addition, we observed increased mRNA expression of GDF15 in primary normal colon tissue from people at increased risk for CRC in comparison with average risk individuals. These findings implicate the importance of a senescence-associated tissue microenvironment and the secretory factor GDF15 in promoting CRC formation. Link: https://doi.org/10.1111/acel.13013
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs

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Abstract Colorectal cancer (CRC) is one of the most common causes of cancer mortality in the world. The incidence is related to increases with age and western dietary habits. Early detection through screening by colonoscopy has been proven to effectively reduce disease-related mortality. Currently, it is generally accepted that most colorectal cancers originate from adenomas. This is known as the "adenoma-carcinoma sequence", and several studies have shown that early detection and removal of adenomas can effectively prevent the development of colorectal cancer. The other two pathways for CRC development ...
Source: Medicina (Kaunas) - Category: Universities & Medical Training Authors: Tags: Medicina (Kaunas) Source Type: research
esco Salvatore Colorectal cancer (CRC) is a leading cause of cancer death worldwide. It includes different subtypes that differ in their clinical and prognostic features. In the past decade, in addition to the conventional adenoma-carcinoma model, an alternative multistep mechanism of carcinogenesis, namely the “serrated pathway”, has been described. Approximately, 15 to 30% of all CRCs arise from neoplastic serrated polyps, a heterogeneous group of lesions that are histologically classified into three morphologic categories: hyperplastic polyps, sessile serrated adenomas/polyps, and the traditional...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Authors: Gravina AG, Dallio M, Tuccillo C, Martorano M, Abenavoli L, Luzza F, Stiuso P, Lama S, Grieco P, Merlino F, Caraglia M, Loguercio C, Federico A Abstract BACKGROUND: Urotensin II (U-II) is a vasoactive peptide that interacts with a specific receptor named UTR. Recently, our group has demonstrated increased UTR expression in both human colon adenocarcinoma cell lines and adenomatous polyps, as well as in colon carcinoma samples if compared to healthy colon samples of the same patients. We also showed that an UTR agonist induced an increase in colon adenocarcinoma cell growth in vitro, whereas the UTR block w...
Source: Minerva Gastroenterologica e Dietologica - Category: Gastroenterology Tags: Minerva Gastroenterol Dietol Source Type: research
Health-Related Complications of Acromegaly—Risk of Malignant Neoplasms Marek Ruchala*† and Kosma Wolinski† Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland The issue of increased risk of benign and malignant neoplasms in patients with acromegaly remains the topic of debate from many years and was addressed by numerous studies. Many of them have shown increase in the cancer incidence. Among particular types of malignancies, thyroid, colorectal, and breast cancer are most commonly indicated as associated with acromegaly. Single ...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
A 67-year-old woman was admitted to our department for one-month duration of asthenia. She was previously operated of upper right lobectomy for a high-grade sarcomatoid carcinoma. The patient was hemodynamically stable. Hemoglobin was 5.4  g/dL, and she was transfused with three blood units. An upper gastrointestinal endoscopy was carried out and it was unremarkable; a colonoscopy was then performed and a voluminous ulcerated polyp with a large base of implantation of the proximal descending colon was seen and removed without compl ications (Fig.
Source: Digestive and Liver Disease - Category: Gastroenterology Authors: Tags: Image of the Month Source Type: research
Conclusions The current review reports recent epidemiological and experimental data supporting the bright future of dietary polyphenols as chemopreventive, anti-inflammatory, immunomodulatory, and anticancer agents in CRC (Figure 1). The polyphenol-rich diet not only may represent a chemopreventive treatment but also has important function on immune system by promoting symbiont and commensal bacterial populations, increases reciprocal interaction between host and microbiota which in turn have important effects on immune function Evidence underlines the use of polyphenols as sensitizers of chemo/radiotherapies paving the w...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
CONCLUSION: Also in our experience adenomatous polyps play a crucial role in the development of colorectal cancer. Therefore, it seems quite essential to avert colorectal cancers gradually. Colonoscopy is a non-invasive method of diagnosis and a treatment of colorectal polyps. Proper and careful colonoscopy examination is indispensable in the discovery of colorectal polyps and subsequent follow-up. Timely and routine colonoscopy is considered as an important approach for thwarting the development of malignant neoplasms. KEY WORDS: Adenomatous polyps, Colorectal cancer, Colorectal polyps, Post-polypectomy. PMID: 309...
Source: Annali Italiani di Chirurgia - Category: Surgery Tags: Ann Ital Chir Source Type: research
Artificial intelligence is making big strides in a variety of medical fields, including radiology, oncology, and even ophthalmology. Now a company called Wision AI, based in Shanghai, Cina, is adapting artificial intelligence vision software to help ...
Source: Medgadget - Category: Medical Devices Authors: Tags: Exclusive GI Informatics Surgery Source Type: blogs
ConclusionDespite the advancement in visualization of anatomy with CT scan and laparoscopic appendicectomy there is still a role for screening colonoscopy in patients greater than 50 years of age with appendicitis particularly if they have associated bowel symptoms or risk factors for CRC.
Source: Annals of Medicine and Surgery - Category: General Medicine Source Type: research
ConclusionsFemale gender, lymphovascular invasion, desmoplastic reaction, criteria for surgery ≥2 and polyp size ≥18 mm were all in complex significant risk factors for lymph node metastasis in T1 colorectal cancer. Acting as a single factor, these variables had no effect to increased risk of metastasis.
Source: ANZ Journal of Surgery - Category: Surgery Authors: Tags: Original Article Source Type: research
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