Endocrine Abstracts

Background: Vitamin D prevents proliferation, promotes differentiation and induces apoptosis of colonic cells. A reduced dietary intake is associated with an increased risk of colorectal cancer (CRC). Recently, we have shown that 25-hydroxyvitamin D-1-alpha hydroxylase (1aOHase) mRNA, which converts vitamin D to its active metabolite, is upregulated in CRC. However, this was based on small number of samples and data on vitamin D receptor (VDR) expression in CRC are inconsisten...

Background: Sporadic colorectal carcinoma (CRC) is more common on the left side of the colon. Acromegaly confers an increased risk of developing CRC but with an increase of right sided disease. IGFBP-3 both regulates tissue exposure to IGF-I and also exerts cellular IGF-l independent pro-apoptotic effects. Whether variation in regional IGFBP-3 expression in the colon may explain the observed pattern of disease in both normal and acromegalic patients is unknown.Aim: 1) To c...

Background:The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis has been increasingly implicated in the development of breast cancer. Previously we have demonstrated the local expression of IGF-I in normal and malignant breast tissue. However the correlation of this local expression with clinical factors has not fully been investigated.Aims: (i) To quantify the mRNA levels of IGF-I in normal and malignant breast tissue and (ii) to identify any correlation betwee...

Background:Recent studies have linked low serum levels of IGFBP-3 with an increased risk of developing breast cancer.In addition to modulating IGF-I bioactivity, IGFBP-3 also exerts IGF-I independent pro-apoptotic effects. Our previous work has demonstrated that IGFBP-3 mRNA expression is significantly down regulated in breast tumours compared to normal breast tissue. It is uncertain, however, how this pattern of expression relates to the pathological and prognostic features o...

Introduction: Cyclooxygenase-2 (COX-2), an inducible enzyme in prostaglandin synthesis, plays a major role in the pathogenesis of sporadic colorectal carcinoma (CRC). COX-2 inhibitors reduce the mortality from sporadic CRC. Acromegaly is associated with an increased risk of CRC, with a preponderance of right sided disease, but COX-2 protein is reduced or absent in acromegalic normal and malignant colonic mucosa. The mechanisms responsible for this are unknown.Aims: (i) To ...

Background: Previously we have demonstrated expression of GH, IGF-1 and ghrelin, but not GHRH, in normal and malignant breast tissue. In vitro studies have suggested an inhibitory effect of ghrelin on proliferation of breast cancer cell lines. However the use of cell lines and dose of ghrelin may not represent physiological conditions.Objectives: (1) To establish a viable method for culturing fresh breast tissue explants, (2) to use this to investigate t...

Background: Recent studies have suggested that an increased level of serum IGF-1 and a decreased level of IGFBP-3 may be associated with an increased risk of developing subsequent breast cancer. However, it is uncertain whether these effects are mediated solely by endocrine actions or whether local effects might also be important. We have previously demonstrated IGF-1 mRNA to be universally expressed in normal breast tissue but in only 50% of cancers. The expression of IGFBP-3...

Background: Acromegalics are at increased risk of developing colorectal neoplasia with an increase of right-sided disease. Several genes are implicated in colorectal neoplasia including components of the GH/IGF-1 axis. It is unclear whether regional variations in neoplasia are explained by variations in local expression of these genes. Aims: To compare the expression of the components of the GH/IGF-1 axis and other putative genes between the left and right colon of patients wi...

Background: Patients with acromegaly have an increased risk of colorectal neoplasia. In non-acromegalic subjects, carcinomas develop from dysplastic tubular adenomas and colonoscopic removal of these reduces the subsequent incidence of carcinoma. The frequency of such screening in acromegaly is controversial and it is uncertain which patients should be considered to be at particular increased risk. Methods: We reviewed the incidence of new colonic lesions amongst our large coh...

Background: We have previously demonstrated colonic expression of the endogenous GH secretagogue, ghrelin, but not the GHS-R, and that ghrelin exerts proliferative effects on colonic epithelial cells. However, whether these are specific to ghrelin, or which genes are affected in response is uncertain.Aims: Determine the specificity of the proliferative effects of ghrelin on colonic epithelial cells, and effects on mRNA levels of the cancer associated ge...