TY - JOUR. T1 - Effect of diets fortified with tomatoes or onions with variable quercetin-glycoside content on azoxymethane-induced aberrant crypt foci in the colon of rats. AU - Femia, A.P.. AU - Caderni, G.. AU - Ianni, M.. AU - Salvadori, M.. AU - Schijlen, E.G.W.M.. AU - Collins, G.. AU - Bovy, A.G.. AU - Dolara, P.. PY - 2003. Y1 - 2003. N2 - Background: Onion and tomato are vegetables widely consumed by humans and epidemiological studies show an inverse association between vegetable consumption and colon cancer risk; however, the effect on colon cancer of diets containing high levels of vegetables like onion and tomato are not clear. Aims of the study: To investigate whether tomatoes and onions,with low or high quercetin-glycoside content, could reduce azoxymethane (AOM)-induced Aberrant Crypt Foci (ACF), preneoplastic lesions in the colon of rats. Methods: Male Fisher 344 rats were fed the following diets: a) high fat (HF) diet (control diet); b) HF diet containing 20 % (w/w) tomatoes ...
Background and aims: The molecular mechanisms underlying the promotion of colorectal carcinogenesis by a high-fat diet (HFD) remain unclear. We investigated the role of the insulin-signal pathway and the c-Jun N-terminal kinase (JNK) pathway, which reportedly play crucial roles in insulin resistance, during colorectal carcinogenesis in the presence of hyperinsulinemia induced by a HFD.. Methods: Azoxymethane-induced aberrant crypt foci formation and cell proliferation in the colonic epithelium were compared between mice fed a normal diet (ND) and mice fed a HFD. A western blot analysis was performed to elucidate the mechanism affecting colorectal carcinogenesis by a HFD.. Results: The number of aberrant crypt foci and the colonic epithelial cell proliferative activity were significantly higher in the HFD group than in the ND group. While the plasma insulin level was significantly higher in the HFD group than in the ND group, a western blot analysis revealed the inactivation of Akt, which is ...
β-Catenin is a key regulator of the cadherin-mediated cell-cell adhesion system and an important element in the Wnt signal transduction pathway. Stabilization and accumulation of cytoplasmic β-catenin, which result from mutations in either the adenomatous polyposis coli or β-catenin genes, are causatively associated with colon carcinogenesis. In the present study, we examined the expression of β-catenin in rat colon tumors induced by azoxymethane in comparison with adjacent normal colon mucosa by immunostaining and immunoblotting. Cytoplasmic and nuclear immunostaining was pronounced in all colon adenoma and carcinoma tissues, whereas antibody binding was limited to membranes at the intercellular borders in normal colon epithelial cells. Increase of the free β-catenin fraction in tumor cells was also indicated by immunoblot analysis of fractionated tissue lysates. Investigation of mutations in the glycogen synthase kinase-3β phosphorylation consensus motif of the β-catenin gene by ...
Severe combined immunodeficiency (Scid) mice have defects in V(D)J recombination and DNA double-strand breaks repair caused by an inherited genetic defect in the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). Scid mice are highly susceptible to development of T-cell lymphomas, and because of the nature of its association with DNA repair and recombination, DNA-PKcs is considered to belong to the caretaker class of tumor suppressor genes. In the present study, the susceptibility of Scid mice to colon carcinogenesis due to administration of azoxymethane (AOM) was investigated. Significantly higher susceptibility in terms of induction of both aberrant crypt foci (ACFs), putative pre-cancerous lesions of the colon and colon cancers was observed as compared with the isogenic strain, C.B-17 mice. The incidences of colon tumors, either adenomas or adenocarcinomas, in Scid and C.B-17 mice after administration of AOM (10 mg/kg body weight/week) for 6 weeks were 87% (26 of 30) and 50% (15 of ...
Cell cycle variations and DNA aneuploidy, were investigated in different phases of azoxymethane (AOM)-induced colon carcinogenesis in rats by flow cytometry. K-ras gene mutations (transitions Gright curved arrow A) were frequently detected in aberrant crypt foci (ACF) initial pre-neoplastic lesions. The fraction of cells in the G2M-phase of the cell cycle was higher in ACF compared to the normal mucosa of control rats. A similar modification of the cell cycle was found in adenomas and adenocarcinomas but, unexpectedly, also in morphologically normal mucosa from AOM-treated animals indicating that AOM treatment permanently modifies cell cycle control in rat colon mucosa. These alterations, however, were not associated with DNA aneuploidy as reported in human sporadic colorectal cancer, suggesting that tumour development in AOM-treated rats is less dependent on aneuploidy.. ...
Purpose: Colon cancer is a major cause of cancer deaths. Dietary factors contribute substantially to the risk of this malignancy. Western-style diets promote development of azoxymethane-induced colon cancer. Although we showed that epidermal growth factor receptors (EGFR) controlled azoxymethane tumorigenesis in standard fat conditions, the role of EGFR in tumor promotion by high dietary fat has not been examined.. Experimental Design: A/J × C57BL6/J mice with wild-type Egfr (Egfrwt) or loss-of-function waved-2 Egfr (Egfrwa2) received azoxymethane followed by standard (5% fat) or western-style (20% fat) diet. As F1 mice were resistant to azoxymethane, we treated mice with azoxymethane followed by one cycle of inflammation-inducing dextran sulfate sodium to induce tumorigenesis. Mice were sacrificed 12 weeks after dextran sulfate sodium. Tumors were graded for histology and assessed for EGFR ligands and proto-oncogenes by immunostaining, Western blotting, and real-time PCR.. Results: Egfrwt mice ...
Inducible nitric oxide synthase (iNOS) is potential target for inflammation and cancer. Previously, we have shown that S,S′‐1,4‐Phenylenebis(1,2‐ethanediyl)bisisothiourea (PBIT) inhibit colon carcinogenesis induced by azoxymethane (AOM). Although, colon cancer inhibitory efficacy of PBIT has been significant, selective iNOS inhibitors do not completely abrogate NO production due to the exogenous bioavailability and NO generation by eNOS in tumor tissues. To create an iNOS selective and multi‐targeted molecule, we have developed a novel isosteric analogue of PBIT, namely PBISe in which sulfur was replaced with selenium. We examined the chemopreventive efficacy of PBISe on AOM‐induced rat colon carcinogenesis model using aberrant crypt foci (ACF) as end point. At seven weeks of age, rats (12/group) were fed the control diet (AIN 76A) and colonic ACF were induced by AOM. Three days after second AOM treatment, rats were fed the diets containing 0, 10 and 20 ppm of PBI‐Se and continued ...
Azoxymethane (AOM) is a colon carcinogen that is used to study the pathogenesis of sporadic colorectal cancer. We have evaluated differential susceptibility to AOM in inbred mice used as progenitors of recombinant/transgenic lines. In experiment 1, male FVB/N, 129/SvJ, C57Bl/6J mice were treated i.p. with 10 mg/kg AOM once per week for 4 weeks and sacrificed after 20 weeks. Only AOM-treated FVB/N mice developed tumors (3.6 tumors/mouse) in distal colon. In experiment 2, A/J, AKR/J, Balb/CJ mice were treated with AOM for 6 weeks and sacrificed after 24 weeks. AOM-treated A/J and Balb/CJ mice developed 9.2 and 1 tumor/mouse, respectively. Despite these differences, tumors had similar morphology regardless of strain. Immunohistochemistry with β-catenin resulted in marked nuclear and cytoplasmic staining of tumor cells in FVB/N. However, fainter and heterogeneous β-catenin staining was observed in A/J tumors, suggesting distinct pathways of tumorigenesis in different strains. Irrespective of ...
Results A single bout of exercise increased the expression and secretion of SPARC in skeletal muscle in both mice and humans. In addition, in an azoxymethane-induced colon cancer mouse model, regular low-intensity exercise significantly reduced the formation of aberrant crypt foci in wild-type mice but not in SPARC-null mice. Furthermore, regular exercise enhanced apoptosis in colon mucosal cells and increased the cleaved forms of caspase-3 and caspase-8 in wild-type mice but not in SPARC-null mice. Culture experiments showed that SPARC secretion from myocytes was induced by cyclic stretch and inhibited proliferation with apoptotic effect of colon cancer cells.. ...
The preventive effect of polysaccharide of Larimichthys crocea swimming bladder (PLCSB) and the increase of this effect by use of resistant starch (RS3) as the carrier for PLCSB on azoxymethane (AOM) and dextran sulfate sodium (DSS)-inducing colon carcinogenesis in C57BL/6 mice has been studied. RS3 microspheres carrying PLCSB (RS3 + PLCSB) were produced and evaluated as a potentially improved colon carcinogenesis therapy for this study. The body weight, colon length, and colon weight of mice were determined, and colonic tissues were histologically observed. The serum levels of proinflammatory cytokines and the inflammation and apoptosis-related genes in colonic tissue were also tested. The PLCSB or RS3 + PLCSB significantly suppressed AOM and DSS-induced body weight loss, colon length shortening and decreased the colon weight to length ratio. PLCSB or RS3 + PLCSB reduced the levels of the serum pro-inflammatory cytokines IL-6, IL-12, TNF-α, and IFN-γ to a greater extent compared with the control
The main objective of this proposal was to investigate the effect of vitamin B6 on colon carcinogenesis in vivo. Two in vivo studies were conducted to determine the role of vitamin B6 as a biological modifier of colon carcinogenesis. It is hypothesized that vitamin B6 may serve as an antioxidant in vivo and will modulate colon carcinogenesis. In the first study, a 2X3 factorial experimental design was used to determine if three different levels of vitamin B6, classified as low, normal and high in conjunction with two different levels of protein intake, classified as normal or high, will affect post-initiation stages of colon carcinogenesis, in Sprague-Dawley rats. Male Sprague-Dawley male were injected with azoxymethane for two weeks (15mg/kg/week) and then one week later they were allocated to different dietary treatment groups. After eight weeks, the effects of dietary treatment on hematological status, oxidative stress markers and antioxidant enzymes, as well as enumeration of preneoplastic ...
Previous work suggests that vagus nerve disruption reduces hepatocyte and oval cell expansion following liver injury. The role of post-neuronal receptor activation in response to liver injury has not been ascertained. We investigated the actions of scopolamine, a non-selective muscarinic receptor antagonist, and specific genetic ablation of a key cholinergic receptor, muscarinic subtype-3 (Chrm3), on azoxymethane (AOM)-induced liver injury in mice. Animal weights and survival were measured as was liver injury using both gross and microscopic examination. To assess hepatocyte proliferation and apoptosis, ductular hyperplasia and oval cell expansion, we used morphometric analysis of BrdU-, activated caspase-3-, H&E-, CK-19- and EpCAM-stained liver sections. Sirius red staining was used as a measure of collagen deposition and its association with oval cell reaction. In AOM-treated mice, both muscarinic receptor blockade with scopolamine and Chrm3 ablation attenuated hepatocyte proliferation and ...
1523 Male Crj: CD-1 (ICR) mice were given a single and low dose of a genotoxic colonic carcinogen azoxymethane (AOM, 10 mg/kg bw, i.p. injection) followed by one-week oral exposure (2% in drinking water) of a non-genotoxic carcinogen dextran sodium sulfate (DSS) to develop an efficient and rapid animal model for colon carcinogenesis. Animals were sequentially sacrificed at Wks 2, 3, 4, 5, 6, 9, 12 and 20 for macroscopic and histopathological examinations. At Wk 3, colonic adenomas developed in 2 of 5 mice (40% incidence with 0.4 ± 0.5 multiplicity). Colonic adenocarcinomas were seen in 2 of 5 mice (40% incidence with 2.0 ± 3.5 multiplicity) at Wk 4. After this time point, the incidence and multiplicity of colonic neoplasms gradually increased with time and reached to 100% incidence at Wk 6. At Wk 20, the multiplicities of adenocarcinoma and adenoma were 5.60 ± 2.42 (100% incidence) and 0.20 ± 0.40 (38% incidence), respectively. Besides these neoplasms, dysplastic lesions and aberrabt crypt ...
As the Dietitians Association of Australia (DAA) kicks off Australias Healthy Weight Week today, new research shows that cooking at home more often means Australians will up their fruit and vegetable intake, helping win the war on weight.. The research, involving more than 1,300 people, found those who spent the most time preparing and cooking meals ate more fruit and vegetables and spent less money on food away from home, compared with those who spent the least amount of time in the kitchen.. "Given more than nine in 10 Australians dont eat the recommended five serves of vegetables a day, and 63 per cent of adults are overweight or obese, and that number is rising, this is important research," Dietitians Association of Australia (DAA) spokesperson and Co-Director of the Priority Research Centre in Physical Activity and Nutrition at the University of Newcastle, Professor Clare Collins said.. Professor Collins said the quality of a persons diet was a good way of predicting weight; and ...
Healthy Weight Week signifies the importance of balance diet and healthy lifestyle. Being healthy does not mean losing weight and going on a diet. It means pursuing livable and sustainable healthy lifestyle through eating well, living actively and feeling good. Bentham Science publishes important research publications that promote this idea. Click here to find related…
Chronic inflammation characterizing patients with inflammatory bowel disease (IBD) represents a major risk factor for the development of colorectal cancer. Mechanisms underlying this neoplastic transformation are not fully understood though studies in experimental models of colon carcinogenesis suggest that inflammatory cell-derived cytokines either directly or indirectly stimulate the uncontrolled growth of cancer cells. Nevertheless, under specific inflammatory conditions, immune cells can boost an anti-tumor immune response with the down-stream effect of eliminating dysplastic and cancerous cells. This review outlines the beneficial and detrimental role of inflammation in colon carcinogenesis.
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Mustard seeds (MS), which are consumed in considerable amounts by the Japanese people that, interestingly, have the longest life expectancy in the world, are known to contain a number of yet not fully defined but quite powerful anti-oxidants. A suspension of extracted MS was found to suppress oxidized-LDL-induced macrophage respiratory burst in vitro, to prevent growth, and to induce apoptotic death of SW480 cells (a human colon cancer cell line), while no such effects were found for normal 3T3 cells. A diet enriched with MS decreased plasma levels of the lipid peroxidation product malonaldehyde in mice exposed to the colon cancer-inducer azoxymethane (AOM). Such a diet also dose-dependently enhanced the activity of several anti-oxidant enzymes, such as superoxide dismutase (SOD), catalase, and GSH-peroxidase and, moreover, reduced AOM-mediated formation of colon adenomas by about 50%. Further studies are required to detail and explore the beneficial effects of MS and their rich content of ...
Preventive intervention of colorectal cancer has become essential as a major portion of the population may develop the disease at some points during their lives. Diet and nutrition play an important role during this multistep colon carcinogenic process. Inhibitory activity of aqueous suspensions of garlic and tomato, individually and in combination, were tested on azoxymethane induced colon carcinogenesis in Sprague-Dawley rats. The effect was observed on aberrant crypt foci (ACF), the preneoplastic lesion. To investigate the mechanism of action of the agents used, cell proliferation and the level of apoptosis were determined and the expression of cyclooxygenase-2 (COX-2) protein was analyzed in the colon. Following treatment, significant inhibition of the level of cell proliferation (P|0.01 in garlic; P|0.001 in tomato and P|0.001 in combination treatment group with respect to the carcinogen control group), significant induction of apoptosis (P|0.01 in garlic treated; P|0.01 in tomato treated and P|0
The dose-response relationship in male F344 rats was determined for the ability of aspirin administered in the diet to prevent azoxymethane (AOM)-induced colon cancer and aberrant crypt foci (ACF) and to reduce prostaglandin E2 (PGE2) levels. Starting at either 7 or 22 weeks of age, the rats received aspirin. All rats received two doses of AOM (15 mg/kg each on days 7 and 14) and were killed on day 36. The lowest concentrations of aspirin to prevent ACF or reduce PGE2 levels were 600 and 400 mg/kg, respectively. To evaluate the prevention of tumors, rats received either 0 or 400 mg/kg aspirin for a total of 39 weeks with AOM (30 mg/kg) administered 7 days after the start of treatment. Aspirin had no effect on the yield of colon tumors. In a second experiment, rats started to receive 0, 200, 600 or 1800 mg/kg aspirin or 1000 mg/kg α-difluoromethylornithine (DFMO) +/- aspirin. Eight and 15 days later, all the rats received 15 mg/kg AOM. Eleven weeks later, animals that were receiving the control ...
Aspirin, naproxen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) are promising chemopreventive agents for individuals at high risk for colorectal cancer (CRC). However, uptake of chronic and continuous NSAID administration to reduce CRC risk is limited by unwanted side effects. Employing novel dosing regimens and an azoxymethane-induced rat colon cancer model, Mohammed and colleagues found that intermittent use of either aspirin or naproxen was highly effective in preventing the progression of colonic adenoma to adenocarcinoma without serious side effects (see the study beginning on page 751). These findings could ultimately impact the standard of preventive care for patients at the adenoma stage (i.e., in high-risk cohorts) to protect against advancement to invasive adenocarcinoma with intermittent NSAID use. The micrograph on the cover depicts hematoxylin and eosin staining of rat colon crypt, hyperplasia, adenoma, and adenocarcinomas that recapitulate the histological progression of ...
It is pertinent however to determine wholesome cooking strategies in addition to consuming habits in methods to not intervene with the nutritious worth of meals Mother Nature intended. Have you ever ever gone through a grueling weight reduction program for a very long time, solely to seek out out later that youve hit a wall when it comes to outcomes. You wont end up tempted almost as much if your forbidden foods arent simply accessible. Correctly, chances are youll need to do additional than merely discovering a meals plan reply program. He did it greater than 50 years earlier. One factor to remember when deciding how one can go about shedding pounds is that there is no such thing as a single greatest way to lose weight. This can be a weight loss program thats loaded with numerous greens and fruits, chemopreventive effects of dietary canola oil on colon cancer development with the lean meats and likewise other protein sources. Due to this actuality, it is best to avoid excessive consumption ...
The goal of this study was to characterize p53 tumor suppressor pathway in colon-specific carcinogen azoxymethane (AOM)-induced mouse colon tumor and to assess the usefulness of this animal model to evaluate novel anti-cancer drugs. The acute exposure of mice to AOM showed no overall induction of p53-regulated genes. Subdued p53 gene activation in the colon corresponded to a drop in the expression of its transcriptional co-activator, p300. The status of p53 pathway was further analyzed using AOM-induced mouse colon tumor and the cell line (AJ02-NM0) generated from the primary tumor. Wild type p53 protein, constitutively expressed in this model, showed no detectable DNA binding activity nor did it activate p21 expression. The cell line studies revealed that p53 activity was inhibited by a constitutive interaction with Mdm2. The p53-activating p19/ARF protein did not appear to have significant effect on the standing of p53 pathway in this cell line. p53 was activated by Doxorubicin, 5-FU and the recently
But early in colon cancer development, these growth-controlling hormones are "lost" and not expressed, disrupting GCCs activity, and, Dr. Waldman believes, contributing to tumor formation. Using two separate mouse models that mimic the development of colon cancer in people, his team showed that GCC signaling blocks such tumors from forming. According to Dr. Waldman, the group found that GCC stops tumors from forming through two different mechanisms. In one case, it controls cell growth, while in the other, it maintains "regulation of genomic integrity.". In one mouse cancer model, the animals carried mutations in the APC gene, which causes colon polyps that frequently lead to colon cancer. Mice in the other cancer-development model were exposed to a commonly used experimental cancer-causing agent, azoxymethane. "We modeled both ways that humans develop colon cancer, and studied the effects of a lack of GCC on the incidence of colon cancer development," he explains.. "We found that in animals ...
Background: The group IIA secretory phospholipase A2 gene, Pla2g2a, confers resistance to intestinal tumorigenesis in the ApcMin/+ mouse model. However, it is unclear how Pla2g2a exerts its tumor-suppressive effects and whether its mode of action dep
Myeloid Translocation Gene, Related-1 (MTGR1) CBFA2T2 is a member of the Myeloid Translocation Gene (MTG) family of transcriptional corepressors. The remaining two family members, MTG8 (RUNX1T1) and MTG16 (CBFA2T3) are identified as targets of chromosomal translocations in acute myeloid leukemia (AML). Mtgr1(-/-) mice have defects in intestinal lineage allocation and wound healing. Moreover, these mice show signs of impaired intestinal stem cell function. Based on these phenotypes, we hypothesized that MTGR1 may influence tumorigenesis arising in an inflammatory background. We report that Mtgr1(-/-) mice were protected from tumorigenesis when injected with azoxymethane (AOM) and then subjected to repeated cycles of dextran sodium sulfate (DSS). Tumor cell proliferation was comparable, but Mtgr1(-/-) tumors had significantly higher apoptosis rates. These phenotypes were dependent on epithelial injury, the resultant inflammation, or a combination of both as there was no difference in aberrant ...
Interestingly, in the investigated effect of consumption of standard diets supplemented with freeze-dried vegetables (peas, spinach, sprouts and broccoli) and carotenoids (all-trans beta-carotene and palm oil carotenoid extract) on surrogate end-point markers for colorectal cancer in an azoxymethane-induced rat model, researchers at the Unilever Research Vlaardingen, illustrated ...
Tanaka Takuji , Sugie Shigeyuki Journal of toxicologic pathology 20(4), 215-235, 2007-12-25 J-STAGE 医中誌Web 参考文献192件 ...
Bielas and colleagues first set out to analyze mutation rates in mitochondrial DNA because they wanted to see if it could act as a surrogate for nuclear DNA as a cancer biomarker. "Cells contain a thousandfold more mitochondrial genetic material than nuclear DNA, so theoretically youd need a thousand times less tissue to get the same genetic information to predict clinical outcomes such as how fast a tumor would progress or whether it would be resistant to therapy," Bielas said.. While mitochondrial DNA proved to be an unreliable stand-in for nuclear DNA as a cancer biomarker, it offers promise as a new drug target.. "If we could increase DNA damage and mutation within the mitochondrial genome, theoretically we could decrease cancer," Bielas said. "Thats what were testing now. This is a whole new hypothesis.". The way mitochondria maintain genetic stability in the face of cancer, Bielas suggests, may be because unlike normal cells, cancer cells do not need oxygen to survive. In fact, cancer ...
Sedlis, A and Stone, D F., "Experimental carcinogenesis in pregnant mice, a preliminary report." (1965). Subject Strain Bibliography 1965. 820 ...
Stanford University School of Medicine found that 63 percent of participants in a study who had a positive body image were more successful at losing and maintaining weight for a year compared to a 26 percent success rate for those who were dissatisfied with their appearance (Source: Shape). How can you work toward develop a positive body image? By realizing that fitness is not a number; it is a way of life. Avoid choosing a "perfect weight" for yourself. Instead, think of your ideal weight as a zone, or a range of weight in which you feel comfortable and beautiful. If you focus on healthy lifestyle instead of a number or a measurement, you can feel truly satisfied ...
Dr. Mathew Meeneghan joins Debbie Bosque at KULM-FM 98.3 to discuss colon cancer on The Doctors Point of View radio show. Dr. Meeneghan talks about colon cancer development, treatment and screening procedures like colonoscopies.
Physicians have long suspected a link between carbohydrate intake and colon cancer development, and a recent study may have illuminated the sought-after link.
In their pioneering work on essential fatty acids, Burr, Burr and Miller compared the nutritional properties of α-eleostearic acid (ELA) to that of its isomer alpha-linolenic acid (ALA). ALA relieved essential fatty acid deficiency; ELA did not.[1] In rats, α-eleostearic acid is converted to a conjugated linoleic acid.[2] The compound has been found to induce programmed cell death of fat cells,[3] and of HL60 leukemia cells in vitro at a concentration of 20 μM.[4] Diets containing 0.01% bitter gourd seed oil (0.006% as α-eleostearic acid) were found to prevent azoxymethane-induced colon carcinogenesis in rats.[5] ...
Routine fortification of food with folic acid was implemented in the U.S. in 1996 to reduce the risk of birth defects in newborns. Widespread fortification in c...
US28 is a constitutively active chemokine receptor encoded by CMV (also referred to as human herpesvirus 5), a highly prevalent human virus that infects a broad spectrum of cells, including intestinal epithelial cells (IECs). To study the role of US28 in vivo, we created transgenic mice (VS28 mice) in which US28 expression was targeted to IECs. Expression of US28 was detected in all IECs of the small and large intestine, including in cells expressing leucine rich repeat containing GPCR5 (Lgr5), a marker gene of intestinal epithelial stem cells. US28 expression in IECs inhibited glycogen synthase 3β (GSK-3β) function, promoted accumulation of β-catenin protein, and increased expression of Wnt target genes involved in the control of the cell proliferation. VS28 mice showed a hyperplastic intestinal epithelium and, strikingly, developed adenomas and adenocarcinomas by 40 weeks of age. When exposed to an inflammation-driven tumor model (azoxymethane/dextran sodium sulfate), VS28 mice developed a
Natural killer (NK) cells are an essential component of innate immunity against cancer development. Many studies have been conducted to evaluate immune-modulating effects using dietary compounds. Our laboratory has been investigating the chemopreventive potential of black raspberries (BRBs) and previously demonstrated their beneficial modulation of genetic and epigenetic biomarkers in patients with colorectal cancer (CRC). The current study investigated their potential on modulating NK cells. To avoid the excessive inflammation caused by the dextran sulfate sodium (DSS) treatment that leads to colitis, we treated the mice with overnight DSS so that it would slightly irritate the colon but still promote colon carcinogenesis with 100% incidence in both the Apc(Min/+) mice and azoxymethane (AOM)-treated mice ...
Colitis is associated with the development of colorectal cancer (CRC) by largely undefined mechanisms that are critical for understanding the link between inflammation and cancer. Intestinal stem cells (ISCs) marked by LGR5 expression are of importance in both the inflammatory response to colitis and progression to colitis-associated colon cancer (CACC). Here, we report in human MUC1-transgenic mouse models of CACC that targeting the MUC1-C oncogenic protein, which is upregulated in inflammation, suppresses the (i) Lgr5+ ISC population, (ii) induction of Myc and core pluripotency stem cell factors, and (iii) severity and progression of colitis to dysplasia and cancer. By extension to human colon cancer cells, we demonstrate that MUC1-C drives MYC, forms a complex with MYC on the LGR5 promoter and activates LGR5 expression. We also show in CRC cells that MUC1-C induces the cancer stem cell (CSC) markers (BMI1, ALDH1, FOXA1, LIN28B) and the OCT4, SOX2 and NANOG pluripotency factors. Consistent ...
Recent research from the laboratory of Michael Karin, PhD, at the University of California, San Diego School of Medicine - the first researcher to demonstrate a molecular link between inflammation and cancer - has identified ...
Pterostilbene : The official website. Everything to know about Pterostilbene : Health benefits ? Dosage ? Where to order the best quality ? And more...
In observance of Healthy Weight Week January 16-20, we asked our members what they are currently doing in regards to the overwhelming levels of obesity around us. View the links below to see what our members are doing.. ...
Pterostilbene has many healthful properties that you discover article after article through your site pterostilbene.com. Some of its healthful properties
This study provides the first evidence that leptin reduces the development of chemically induced precancerous lesions in colon, perhaps through decreased insulinemia, and thus does not support an important role for leptin in carcinogenesis promotion. Moreover, the study indicates that leptin is not …
In exploring the genetics of mitochondria - the powerhouse of the cell - researchers at Fred Hutchinson Cancer Research Center have stumbled upon a finding that challenges previously held beliefs about the role of mutations in cancer development.. For the first time, researchers have found that the number of new mutations are significantly lower in cancers than in normal cells.. "This is completely opposite of what we see in nuclear DNA, which has an increased overall mutation burden in cancer," said cancer geneticist Jason Bielas, Ph.D., whose findings are published in the June 7 issue of PLoS Genetics.. Mutations are changes in the genetic sequence of a cells genome and can occur as a result of environmental exposure to viruses, radiation and certain chemicals, or due to spontaneous errors during cell division or DNA replication.. Mitochondria, which are primarily responsible for the cells energy production, are semi-autonomous; similar to the nucleus, they have their own set of DNA, which ...
SEATTLE - June 7, 2012 - In exploring the genetics of mitochondria - the powerhouse of the cell - researchers at Fred Hutchinson Cancer Research Center have stumbled upon a finding that challenges previously held beliefs about the role of mutations in cancer development.
PRIMARY OBJECTIVES:. I. To determine mean percentage change from baseline in prostaglandin E2 (PGE2) within ACF pre and post 30 days of curcumin administration at a specified dose.. SECONDARY OBJECTIVS:. I. To determine mean percentage change from baseline in 5-hydroxy-eicosatetraenoic acid (5-HETE) within ACF pre and post 30 days of curcumin administration at a specified dose.. II. To determine mean percentage change from baseline in PGE2 and 5-HETE within comparison normal mucosa pre and post 30 days of curcumin administration at a specified dose.. III. To quantify corresponding enzyme changes in the cyclooxygenases (COX-1, COX-2,) and lipoxygenase (5-LOX) protein abundance. Semi-quantitative changes in these proteins will be measured by western blotting and correlated with changes in prostaglandins and leukotrienes respectively.. IV. Document changes in total ACF number. V. Determine proliferation by Ki-67 IHC in rectal mucosa pre and post therapy and correlate with changes in ACF number and ...
Potential application of targeting miRNAs is increasing in gene therapy testing and preclinical studies. The development of mouse models generates key biological and molecular events based on human conditions. The efficacy of miRNA-mediated CRC therapy is following current technologies through various strategies.. Traditional preclinical mouse models of CRC induced by colitis - associated cancer (CAC) have been established with two drugs of azoxymethane (AOM) and DSS as the results of mutations containing PI3K, K-ras and catenin pathways. Another CDX2P-NLS Cre;Apc+/loxP (CPC; Apc) mouse model harbors a truncating mutation affecting one APC allele [131]. Compared to normal tissues, 57 miRNAs are aberrantly expressed in tumors in the AOM/DSS model while 35 miRNAs are aberrantly expressed in polyps from CPC; Apc mice [132]. Among the overexpressed miRNAs, miR-135b is consistently the highest expressed one in both models. High miR-135b expression is correlated with tumor stage and poor overall ...
Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat-containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota. Activation of the inflammasome and IL18 signaling pathways is largely protective in colitis-associated colorectal cancer, whereas excessive inflammation driven by the inflammasome or the IL1 signaling pathways promotes breast cancer, fibrosarcoma, gastric carcinoma, and lung metastasis in a context-dependent manner. The clinical relevance of inflammasomes in multiple forms of cancer highlights their therapeutic promise as molecular targets. In this review, we explore the ...
Human Epidermal growth factor Receptor type 2 (HER2) is over expressed in 20.0-30.0% of breast cancers and is currently evaluated histopathologically. Immunohistochemistry and fluorescence in situ hybridization require invasive enucleation of the tumor tissue and may be affected by heterogeneity. Serum marker tests are more objective because of the uniformity of the study material. Serum HER2 levels are important for breast cancer care. However, the clinical utility of serum HER2 testing is unclear. We evaluated serum HER2 as a marker of therapeutic response in breast cancer.
Colitis-associated colon cancer (CAC) develops as a result of inflammation-induced epithelial transformation, which occurs in response to inflammatory cytokine-dependent downregulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and subsequent suppression of prostaglandin metabolism. Agents that both enhance 15-PGDH expression and suppress cyclooxygenase-2 (COX-2) production may more effectively prevent CAC. Synthetic triterpenoids are a class of small molecules that suppress COX-2 as well as inflammatory cytokine signaling. Here, we found that administration of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-C28-methyl ester (CDDO-Me) suppresses CAC in mice. In a spontaneous, inflammation-driven intestinal neoplasia model, deletion of ...