http://aiocm.org/member/Immunity,%20Inflammation,%20and%20Cancer.pdf

Immunity, Inflammation, and Cancer

Our appreciation of the physiological functions of estrogens and the mechanisms through which estrogens bring about these functions has changed during the past decade. Just as transgenic mice were produced in which estrogen receptors had been inactivated and we thought that we were about to understand the role of estrogen receptors in physiology and pathology, it was found that there was not one but two distinct and functional estrogen receptors, now called ERα and ERβ. Transgenic mice in which each of the receptors or both the receptors are inactive have revealed a much broader role for estrogens in the body than was previously thought. This decade also saw the description of a male patient who had no functional ERα and whose continued bone growth clearly revealed an important function of estrogen in men. The importance of estrogen in both males and females was also demonstrated in the laboratory in transgenic mice in which the aromatase gene was inactivated. Finally, crystal structures of the estrogen r...

Mechanisms of Estrogen Action

https://www.gastrojournal.org/article/S0016-5085(10)00176-9/pdf

Inflammation and Colon Cancer

Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events.

I. Introduction THE insulin-like growth factors (IGFs) and their receptors and binding proteins constitute a family of cellular modulators that play essential roles in the regulation of growth and development. The IGF ligands include three structurally related peptides: insulin, IGF-I, and IGF-II. Unlike insulin, IGF-I and IGF-II are expressed ubiquitously, albeit in a highly regulated manner (see reviews in Refs. 1-5). The biological functions of the IGFs are mediated by a family of transmembrane receptors, which includes the insulin, IGF-I, and IGF-II/mannose-6-phosphate (M-6-P) receptors. While the IGF-I receptor is the primary mediator of IGF action, the insulin and IGF-II/M-6-P receptors may also mediate some of these functions (Fig. 1) (6, 7). The biological actions of the IGFs are modulated by a family of at least six IGF-binding proteins (IGFBPs) that are found in the circulation and in extracellular compartments and are produced by most tissues. The IGFBPs are capable of inhibiting or enhancing I...

Molecular and cellular aspects of the insulin-like growth factor I receptor

https://www.gastrojournal.org/article/0016-5085(91)90004-5/pdf

Establishment and characterization of a human carcinoid in nude mice and effect of various agents on tumor growth.

https://www.gastrojournal.org/article/0016-5085(92)90744-J/pdf

Characterization of insulinlike growth factor I receptors in human colon cancer

We have measured gastrin receptors (GR) in surgical specimens from 67 patients with primary colon cancers in order to determine the clinical significance of GR in colon cancer. GR analysis was performed on these specimens, and 22 cancers (32.8%) had no detectable GR. Thirty-eight cancers (56.7%) had high-affinity (Kd less than 1.0 nM) levels of GR. Seven cancers (10.4%) had only low-affinity GR (Kd greater than 1.0 nM). Twenty patients (29.9%) had cancers with GR greater than 10 fmol/mg protein. Mean GR content was significantly greater (11.8 +/- 2.9 fmol/mg protein) in Dukes' Stage A and B cancers when compared to Stage C and D cancers (6.2 +/- 1.6 fmol/mg protein). A significantly greater percentage (52.4%) of patients in the early stages (A and B) had tumors with greater than 10 fmol/mg protein compared to patients with more advanced (C and D) cancers (19.6%). GR content did not correlate with histological differentiation, patient age, or preoperative carcinoembryonic antigen levels. No difference in the GR content was noted between left and right colon cancers or in patients of different sex or race. GR content of normal colon mucosa correlated with the GR content of colon cancers from the same surgical specimen, suggesting that these tumors maintain their normal complement of GR. In the early period of follow-up, 12 of 43 (28%) Stage C and D patients with GR less than 10 fmol/mg protein have died, whereas all 8 Stage C and D patients with GR greater than 10 fmol/mg protein are alive. GR content of colon cancers may have prognostic significance and may identify a group of patients with colon cancer that may benefit from hormonal therapy with antigastrin drugs.

https://cancerres.aacrjournals.org/content/canres/49/2/488.full.pdf

Clinical significance of gastrin receptors in human colon cancers.

https://www.gastrojournal.org/article/0016-5085(93)90971-E/pdf

Insulinlike growth factors and binding proteins in colon cancer

Insulin-like growth factor-binding protein-4 (IGFBP-4) is expressed in MCF-7 human breast cancer cells, and treatment of these cells with 17β-estradiol (E2) resulted in induction of IGFBP-4 gene expression (>3-fold) and protein secretion (>6-fold). To identify genomic sequences associated with E2 responsiveness, the 5′-promoter region (−1214 to +18) of the IGFBP-4 gene was cloned into a vector upstream from the firefly luciferase reporter gene, and E2 induced a 10-fold increase in luciferase activity in MCF-7 cells transiently transfected with this construct. Deletion analysis of this region of the IGFBP-4 gene promoter identified two GC-rich sequences at −559 to −553 and −72 to −64 that were important for E2-induced trans-activation. Gel mobility shift assays using 32P-labeled −569 to −540 and −83 to −54 oligonucleotides from the IGFBP-4 gene promoter showed that Sp1 protein bound these oligonucleotides to form a retarded band, and the intensity of the band was competitively decreased after coincubation ...

/pdf/transcriptional-activation-of-insulin-like-growth-factor-31l691cj4v.pdf

Pomila Singh

Papers

Establishment and characterization of a human carcinoid in nude mice and effect of various agents on tumor growth.

Characterization of insulinlike growth factor I receptors in human colon cancer

Clinical significance of gastrin receptors in human colon cancers.

Insulinlike growth factors and binding proteins in colon cancer

Transcriptional Activation of Insulin-Like Growth Factor-Binding Protein-4 by 17β-Estradiol in MCF-7 Cells: Role of Estrogen Receptor-Sp1 Complexes