Biomedical subjects

Anne-Maria Pajari

Publications and source records attributed to Anne-Maria Pajari.

6 recordsLinked to original sources

PubMed2006

Nuclear factor kappaB is downregulated and correlates with p53 in the Min mouse mucosa during an accelerated tumor growth.

The nuclear factor kappaB signaling pathway has gained attention for its role in the carcinogenic process. We have measured the protein levels of the p65 subunit during a growth of adenomas in the Min mouse model for colon cancer. To study how an accelerated growth of adenomas affect cell signalling, adenoma growth was increased by an inulin diet (10%) that we have shown previously to be a promotor of adenoma formation. In our study, the association between NF-kappaB, p53, beta-catenin, Fas and COX-2 were evaluated by measuring their protein levels in 9- and 15-week old Min mouse adenomas and surrounding mucosa. The amount of p65 rouse between 9- and 15-weeks in the mucosa of the control-fed mice (p = 0.032). The inulin-fed mice had less p65 in the nucleus of the mucosa at 15 weeks of age compared to the control (p = 0.064), although the adenomas were significantly larger (1.46 mm +/- 0.12 for inulin, 0.97 mm +/- 0.12 for control, p < 0.001). Nuclear p65 correlated positively with nuclear p53 in the mucosa (p < 0.001) and adenoma (p < 0.001) tissues. Also, p65 correlated positively with nuclear beta-catenin in the mucosa (p = 0.012) and the adenoma (p = 0.001). Fas expression increased in the inulin group between 9-15 weeks (p = 0.034) and correlated negatively with p65 (p = 0.03). The amount of COX-2 in the adenoma tissue increased between 9-15 weeks and did not correlate with p65. The results suggest that p65 is involved in a p53-dependent apoptotic response in the Min mouse.

Adenoma↗

PubMed2006

Ellagic acid and natural sources of ellagitannins as possible chemopreventive agents against intestinal tumorigenesis in the Min mouse.

Ellagic acid has been shown to have chemopreventive effects in various experimental cancer models. We wanted to see whether pure ellagic acid and natural ellagitannins from cloudberry (Rubus chamaemorus) seed and pulp have any effect on adenoma formation in Apc-mutated Min mice. From the age of 5 wk, the mice were fed either a control diet, a diet containing pure ellagic acid at 1,564 mg/kg, or diets containing 4.7% (wt/wt) cloudberry seeds or 5.3% cloudberry pulp. The concentrations of ellagitannins and free ellagic acid in the seed diet were 807 and 42 mg/kg and in the pulp diet 820 and 34 mg/kg, respectively. After the 10-wk feeding period, ellagic acid had no effect on the number or size of adenomas in the distal or total small intestine, but it increased adenoma size in the duodenum when compared with the control diet (1.50+/-0.29 vs. 1.16+/-0.31 mm; P=0.029). Neither cloudberry seed nor pulp diets had any effect on the adenoma formation. Chemopreventive effects and mechanisms of whole cloudberry and other similar sources of phenolic compounds should, however, be studied, further taking into account food matrix and interactions with other dietary constituents that may be involved in the bioavailability and metabolism of ellagitannins.

Adenoma↗

PubMed2005

The plant lignans matairesinol and secoisolariciresinol administered to Min mice do not protect against intestinal tumor formation.

The lignans matairesinol (MAT) and secoisolariciresinol (SECO) were fed to Min mice at 0.02% (w/w) in diet to study their effects on intestinal tumor development. The mean number (67 vs. 51, P=0.052) and size (1.4 vs. 1.2 mm, P=0.011) of tumors in the MAT group was elevated when compared with the control group. Tumor formation of the SECO group did not differ from the control group. Intake of MAT increased the level of both MAT and enterolactone in the plasma while SECO feeding increased SECO, enterodiol, and enterolactone (P=0.001). These results showed that MAT or SECO do not prevent intestinal carcinogenesis in Min mice and that MAT may have adverse effects.

4-Butyrolactone↗

PubMed2005

Promotion of adenoma growth by dietary inulin is associated with increase in cyclin D1 and decrease in adhesion proteins in Min/+ mice mucosa.

We have earlier shown that dietary fructo-oligosaccharide inulin enhances adenoma growth in multiple intestinal neoplasia (Min/+) mice. To further explore inulin-induced early biochemical changes in the normal-appearing mucosa, Min/+ mice were fed from the age of 5 weeks to the ages of 8 and 15 weeks a control diet or an inulin-enriched diet (10% w/w). In addition, the wild-type littermates were fed with the same diets until the age of 8 weeks, in order to determine whether similar changes happen both in the wild-type and Min/+ mice. The mucosa without adenomas was collected and fractionated to nuclear, cytosolic and membrane pools. The protein levels of beta-catenin, cyclin D1 and E-cadherin were determined by Western blotting at both time points, and immunohistochemical stainings were done for 8-week-old mice. The promotion of adenoma growth by inulin (week 15, 1.3-fold increase, P=.0004) was associated with accumulation of cytosolic and nuclear beta-catenin, and increased amount of cytosolic cyclin D1 (1.5-fold increase, P=.003) in the normal-appearing mucosa of the Min/+ mice. Furthermore, inulin feeding reduced the membranous pools of beta-catenin and E-cadherin. Also in the wild-type mice the drop in membranous beta-catenin was clear (P=.015), and, moreover, a subset of crypts had enhanced nuclear beta-catenin staining. These data indicate that dietary inulin can already activate in the normal-appearing mucosa beta-catenin signaling, which in the presence of Apc mutation induces adenoma growth and even in the wild-type mice direction of the changes is similar.

Adenoma↗

PubMed2005

Effects of a flaxseed mixture and plant oils rich in alpha-linolenic acid on the adenoma formation in multiple intestinal neoplasia (Min) mice.

Flaxseed is a dietary source of possible chemopreventive compounds such as lignans and alpha-linolenic acid (ALA). To study the effects of a flaxseed mixture on adenoma formation in multiple intestinal neoplasia mice, the mice were fed a diet containing 2.7 % flaxseed, 4.5 % fibre and 3.7 % ALA. To elucidate the effect of oils of the mixture we also composed a diet without flaxseed but with the same oil composition. The median number of adenomas in the small intestine was fifty-four for the control group, and thirty-seven (P=0.023) and forty-two (P=0.095) for flaxseed and oil groups, respectively. Compared with controls (1.2 mm), the adenoma size was smaller in the flaxseed (0.9 mm; P=0.002) and oil (1.0 mm; P=0.012) groups. Both diets changed the proportions of n-3 and n-6 fatty acids in the colonic mucosa. Membrane beta-catenin and protein kinase C (PKC)-zeta levels were reduced in the adenoma v. mucosa (P<0.05), and an inverse association was found between the membrane PKC-zeta in the mucosa and the adenoma number (r -0.460, P=0.008, n 32). Only the flaxseed diet increased lignan levels in the caecum (P=0.002) and in plasma (P=0.002) but they were not associated with tumour formation. The results suggest that the preventive effect of flaxseed on colon carcinogenesis may be due to the oil part of flaxseed, and the loss of beta-catenin and PKC-zeta from the membranes of the mucosal tissue may play a permissive role in intestinal tumour development.

Actins↗

PubMed2003

Promotion of intestinal tumor formation by inulin is associated with an accumulation of cytosolic beta-catenin in Min mice.

Inulin, polydisperse beta (2-1) fructan, has been suggested to protect against colon carcinogenesis and is currently used in a number of food applications. However, the data regarding the role of inulin in intestinal carcinogenesis remains controversial since the results of our previous study suggested that inulin promotes intestinal tumor formation in Min mice, an animal model for intestinal cancer with a mutation in the Apc tumor suppressor gene (Carcinogenesis 2000;21:1167-73). In our present study, we further examined the effects of inulin on intestinal tumor formation in Min mice by carefully analyzing beta-catenin expression and cellular localization at 3 different time points during the tumorigenic process. Min mice were fed a high-fat inulin-enriched (10% w/w) diet or the high-fat diet without any added fiber from the age of 6 weeks to the ages of 9, 12 or 15 weeks. The results showed that inulin significantly increased the number (by 20%) and especially the size (by 44%) of adenomas in the small intestine. At week 15, the promotion of tumor development was accompanied by an accumulation of cytosolic beta-catenin in the adenoma tissue. In the normal appearing mucosa, levels of membrane beta-catenin and PCNA were reduced in the inulin-fed mice, possibly indicating impaired enterocyte migration. These data do not support the earlier suggestions on the cancer preventive effects of inulin and emphasize the need for further research and evaluation where health claims for inulin are concerned.

Adenoma↗