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Garlic
Published in Robert E.C. Wildman, Richard S. Bruno, Handbook of Nutraceuticals and Functional Foods, 2019
Sharon A. Ross, Craig S. Charron
Preclinical models (Table 5.2) provide some of the most compelling evidence that garlic and its related sulfur components suppress cancer risk and alter the biological behavior of tumors. Overall, garlic and its associated sulfur components have been found to suppress the incidence of mammary, colon, skin, uterine, esophageal, lung, renal, forestomach, and liver cancers.86–94 Aberrant crypt foci (ACF) are a proposed early preneoplastic lesion of adenoma-carcinoma in humans and chemically induced colon cancer in rodents. In many preclinical studies, both water- and lipid-soluble allyl sulfur compounds administered to animals through their diet have been reported to inhibit ACF.95–97
Gastrointestinal Tract
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Judit E. Markovits, Graham R. Betton, Donald N. McMartin, Theresa Boulineau
Hyperproliferation due to disturbance of the orderly proliferation and differentiation may be visualized as individual crypts or clusters of crypts that are larger than normal, often with a slit-like opening (Figure 11.6b,c; Fenoglio-Preiser and Noffsinger 1999). In a clinical setting, aberrant crypt foci (ACFs) may be visualized at the time of endoscopy or as in nonclinical samples, with en face preparations that are stained with methylene blue as darkly stained clusters of crypts. These crypts contain abnormal mucus and microsatellite instability (repeats of short DNA sequences) and often have RAS mutations. Based on morphological and genetic evidence as well as the circumstances under which lesions are found in a larger number (after carcinogen treatment of animals or in patients with high risk of colon cancer), ACF is considered to be a preneoplastic lesion (Alrawi et al. 2006).
Development of palliative medicine in the United Kingdom and Ireland
Published in Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita, Textbook of Palliative Medicine and Supportive Care, 2015
53 Nascimbeni R, Donato F, Ghirardi M, Mariani P, Villanacci V, Salerni B. Constipation, anthranoid laxatives, melanosis coli, and colon cancer: A risk assessment using aberrant crypt foci. Cancer Epidemiol Biomarkers Prev. 2002;11(8):753-757. PubMed PMID: 12163329.
5-Hydroxymethylfurfural (HMF) formation, occurrence and potential health concerns: recent developments
Published in Toxin Reviews, 2021
Ankit Choudhary, Vikas Kumar, Satish Kumar, Ishrat Majid, Poonam Aggarwal, Sheenam Suri
At the preclinical level, HMF and its derivative, SMF, have been referred to as potent carcinogens (Shapla et al.2018). The end product of Maillard reaction i.e. HMF promotes the growth of human tumor cells and also found to have the opposite effect against human tumor cells (Markowicz et al.2012). Micro-adenomas and aberrant crypt foci (ACF) act as markers in the multistep stage which occurs during colon cancer. A study concluded that the incorporation of small doses of HMF and SMF in multiple intestinal neoplasia mice resulted in an increase in the formation of small adenomas and flat ACF (Svendsen et al.2009). When HMF was administered orally to F344 female rats, it resulted in an increment in both size and number of ACF (Zhang et al.1993). Adenomas formation in small and large intestines due to mutation in tumor suppressor gene i.e. adenomatous polyposis coli (ACP) which resulted in similar human familial adenomatous polyposis syndrome (Paulsen et al.2005).
Dietary Garcinol Arrests Pancreatic Cancer in p53 and K-ras Conditional Mutant Mouse Model
Published in Nutrition and Cancer, 2018
Nadia Saadat, Sarah Akhtar, Arvind Goja, Nurul H. Razalli, Andreea Geamanu, Doina David, Yimin Shen, Smiti Vaid Gupta
Papilloma formations were observed in KPC mice. The histology and pathology of these papilloma’s was quite similar to the metaplastic, columnar, and glandular gastric tumors earlier reported in a study with SMAD 3 zinc deficient mice (24). Similar tumors have also been reported in p53 null and zinc deficient mice with N-nitrosomethylbenzylamine (NMBA) administration (25). Fore stomach in rodents is considered as a dilation of the esophagus and is comparable to human esophageal/stomach junction. This portion of stomach is more sensitive than the esophagus in mice, although both are lined by squamous epithelium (25). Intestinal obstruction is the major cause of weight loss and death in KPC mice. All the Garcinol fed mice (KGr) mice survived the study and did not show any of these complications. In a research study conducted on a colon cancer mouse model, researchers have reported reduced tumor size, reduction in aberrant crypt foci formation after treatment with Garcinol along with reduced inflammation. Furthermore, they described decreased levels of COX2, cyclin D1, VEGF, and Wnt/β-catenin as possible mechanisms behind these effects (26). Reduced papilloma formations and inflammation in PC warrants further investigation and can be a very useful finding for advanced stage PC management.
PPARγ-activation increases intestinal M1 macrophages and mitigates formation of serrated adenomas in mutant KRAS mice
Published in OncoImmunology, 2018
Tobias Gutting, Christian A. Weber, Philip Weidner, Frank Herweck, Sarah Henn, Teresa Friedrich, Shuiping Yin, Julia Kzhyshkowska, Timo Gaiser, Klaus-Peter Janssen, Wolfgang Reindl, Matthias P. A. Ebert, Elke Burgermeister
Prolonged RAS-activation can result in oncogene-induced senescence (OIS).4 Since most polyps did not progress to carcinoma, we performed IHC on tissue sections of RAS and RAS PPARΔIEC mice (n≥3 per genotype) with Abs detecting P-ERK1/2 as a marker of active RAS-signaling and P21 (CIP1/WAF1) as a marker for OIS (Fig. 3A). IHC staining underwent quantitative analysis for absolute numbers of cases having high (scores +2,+3) or low (scores 0,+1) positivity in polyps vs. the non-malignant mucosa (*p < 0.05, Fisher Exact test). Polyps were summarized from the following morphologies; hyperplastic polyp (HPP), serrated adenoma (SA) and sessile serrated adenoma (SSA). Aberrant crypt foci (ACF) and tubular adenomas (Ad) were infrequent and excluded from the analysis. Notably, the staining positivity (Fig. 3B) of P-ERK1/2 in polyps was reduced, while P21 was increased compared with the non-malignant mucosa, indicative of an arrest of RAS-ERK1/2-driven proliferation in favour of RAS-induced senescence. No difference was stated between polyps of the two genotypes (not shown). These data suggested that PPARγ is dispensable once adenoma formation has been initiated by mutant RAS, in contrast to its immunoregulatory role in the hyperplastic pre-malignant mucosa where it counteracts mutant RAS effects.