Nononcogenic restoration of the intestinal barrier by E. coli-delivered human EGF.

Although mucoactive proteins, such as epidermal growth factor (EGF), could improve clinical outcomes of intestinal ulcerative diseases, their gastrointestinal application is limited because of their proteolytic digestion or concerns about tumor promotion. In the present study, ATP-binding cassette (ABC) transporter-linked secretion of human EGF from probiotic Escherichia coli (EGF-EcN) was created to promote beneficial actions of the EGF receptor, which is notably attenuated in patients with intestinal ulcerative injuries. Preventive and postinjury treatment with EGF-EcN alleviated intestinal ulcers and other readouts of disease severity in murine intestinal ulcer models. EGF-EcN administration promoted the restitutive recovery of damaged epithelial layers, particularly via upward expansion of highly proliferating progenitor cells from the lower crypts. Along with the epithelial barrier benefit, EGF-EcN improved goblet cell-associated mucosal integrity, which controls the access of luminal microbiota to the underlying host tissues. Despite concern about the oncogenic action of EGF, EGF-EcN did not aggravate colitis-associated colon cancer; instead, it alleviated protumorigenic activities and improved barrier integrity in the lesions. All findings indicate that probiotic bacteria-based precision delivery of human EGF is a promising mucosal intervention against gastrointestinal ulcers and malignant distress through crypt-derived barrier restoration.

Modulating the therapeutic response of tumours to dietary serine and glycine starvation.

The non-essential amino acids serine and glycine are used in multiple anabolic processes that support cancer cell growth and proliferation (reviewed in ref. 1). While some cancer cells upregulate de novo serine synthesis, many others rely on exogenous serine for optimal growth. Restriction of dietary serine and glycine can reduce tumour growth in xenograft and allograft models. Here we show that this observation translates into more clinically relevant autochthonous tumours in genetically engineered mouse models of intestinal cancer (driven by Apc inactivation) or lymphoma (driven by Myc activation). The increased survival following dietary restriction of serine and glycine in these models was further improved by antagonizing the anti-oxidant response. Disruption of mitochondrial oxidative phosphorylation (using biguanides) led to a complex response that could improve or impede the anti-tumour effect of serine and glycine starvation. Notably, Kras-driven mouse models of pancreatic and intestinal cancers were less responsive to depletion of serine and glycine, reflecting an ability of activated Kras to increase the expression of enzymes that are part of the serine synthesis pathway and thus promote de novo serine synthesis.

[Medical aspect of food starch]. / Meditsinskii aspeky pishchevogo krakhmala.

In the review are considered aspects of food starch such as its relationship with cancer of the large intestine, its absorption, digestion and metabolism, influence of starch on the composition and biochemical characteristics of microbiocenosis.

The effect of switching between a phytohemagglutinin-containing and a control diet on the growth and lipid content of a Krebs II lymphosarcoma tumor.

The present study concerns the importance of the timing of feeding mice a PHA-containing diet (7 mg g-1 diet) on tumor formation. The major decrease in tumor weight occurred in mice fed on the PHA diet for 11 days. A marked reduction was also observed in animals pre-fed for 3 days with PHA before tumor cells were injected and the diet then changed to lactalbumin, La. A large decrease in tumor weight was also evident when a change of diet from La to PHA was made on the day of tumor cell inoculation. Despite the presence of the developing tumor PHA was able to induce hyperplasia of the small intestine in all groups of animals fed PHA during a part or the whole of the experiment. The dry weights of tumors attained in each of the experimental groups plotted as a function of duration of PHA feeding, and the percentage lipid content of the tumors, mirrored almost exactly one another, suggesting that the availability of essential lipid material is severely reduced by the lectin. This would appear to have a major effect on the observed reduction in tumor growth.

Effects of rice bran hemicellulose on 1,2-dimethylhydrazine-induced intestinal carcinogenesis in Fischer 344 rats.

The effect of rice bran hemicellulose (RBH) on 1,2-dimethylhydrazine- (DMH) induced intestinal carcinogenesis was studied in male Fischer 344 rats. Rats were fed a basal control diet or a diet containing 2% or 4% RBH at five weeks of age. At 6 weeks of age, all animals were given an intraperitoneal injection of DMH (20 mg/kg body wt) at weekly intervals for 20 weeks and autopsied 7 weeks after the last injection. The incidence of DMH-induced colon tumors was significantly lower in rats fed the 4% RBH diet than in rats fed the basal control diet (p < 0.05). The number of colon tumors per rat was also significantly lower in rats fed the 4% RBH diet than in rats fed the basal control diet (p < 0.05). The present study suggested that the water-soluble RBH played a preventive role in DMH-induced large bowel carcinogenesis in Fischer 344 rats.

Multifocal small bowel lymphoma and latent celiac sprue.

Malignant small intestinal lymphoma may complicate or antedate clinical recognition of celiac sprue, a disorder becoming increasingly diagnosed as a subclinical or occult disease. A 73-yr-old woman with previously resected jejunoileal lymphoma and normal proximal small bowel biopsy specimens was given a high-gluten diet containing 40 g of added gluten daily for 4 wk. This caused small intestinal biopsy abnormalities typical of celiac sprue; the abnormalities resolved 6 wk later with a gluten-free diet. This indicates that latent celiac sprue may be present in some patients with lymphoma and suggests that the association of celiac sprue and lymphoma may be more frequent than is currently appreciated.