Eli Lilly and Company

About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Receptor. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.

Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice.

Abstract: Epidermal growth factor receptor (EGFR) regulates the growth and progression of human transitional cell carcinoma (TCC) of the bladder. We have shown that therapy targeting EGFR inhibited the growth of human TCC established orthotopically in nude mice. The purpose of this study was to evaluate whether EGFR-directed therapy affects angiogenesis associated with the growth and metastasis of human TCC. We determined the cytostatic effect and the effect on production of angiogenic factors after in vitro treatment of the human TCC cell line 253J B-V with MAb C225, a chimerized monoclonal anti-EGFR antibody. The 253J B-V cells were implanted orthotopically into athymic nude mice, and established tumors (4 weeks) were treated with i.p. MAb C225. Expression of the angiogenic factors vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and basic fibroblast growth factor (bFGF) was evaluated by immunohistochemistry and in situ mRNA hybridization analyses and correlated with microvessel density evaluated after immunohistochemical staining with anti-CD31. In vitro treatment with MAb C225 inhibited mRNA and protein production of VEGF, IL-8, and bFGF by 253J B-V cells in a dose-dependent manner. MAb C225 therapy of nude mice with established TCCs growing orthotopically resulted in inhibition of growth and metastasis compared with controls (P <0.0005). VEGF, IL-8, and bFGF expression was significantly lower in treated tumors than in controls. The down-regulation of these angiogenic factors preceded the involution of blood vessels. These studies indicate that therapy with anti-EGFR MAb C225 has a significant antitumor effect mediated, in part, by inhibition of angiogenesis.

Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure.

Abstract: Histomorphometry and CT of 51 paired iliac crest biopsy specimens from women treated with teriparatide revealed significant increases in cancellous bone volume, cancellous bone connectivity density, cancellous bone plate-like structure, and cortical thickness, and a reduction in marrow star volume. Introduction: We studied the ability of teriparatide (rDNA origin) injection (rhPTH(1-34), TPTD) to improve both cancellous and cortical bone in a subset of women enrolled in the Fracture Prevention Trial of postmenopausal women with osteoporosis after a mean treatment time of 19 months. This is the first report of a biopsy study after treatment with teriparatide having a sufficient number of paired biopsy samples to provide quantitative structural data. Methods: Fifty-one paired iliac crest bone biopsy specimens (placebo (n 19), 20 g teriparatide (n 18), and 40 g teriparatide (n 14)) were analyzed using both two-dimensional (2D) histomorphometry and three-dimensional (3D) microcomputed tomography (CT). Data for both teriparatide treatment groups were pooled for analysis. Results and Conclusions: By 2D histomorphometric analyses, teriparatide significantly increased cancellous bone volume (median percent change: teriparatide, 14%; placebo, 24%; p 0.001) and reduced marrow star volume (teriparatide, 16%; placebo, 112%; p 0.004). Teriparatide administration was not associated with osteomalacia or woven bone, and there were no significant changes in mineral appositional rate or wall thickness. By 3D cancellous and cortical bone structural analyses, teriparatide significantly decreased the cancellous structure model index (teriparatide, 12%; placebo, 7%; p 0.025), increased cancellous connectivity density (teriparatide, 19%; placebo, 14%; p 0.034), and increased cortical thickness (teriparatide, 22%; placebo, 3%; p 0.012). These data show that teriparatide treatment of postmenopausal women with osteoporosis significantly increased cancellous bone volume and connectivity, improved trabecular morphology with a shift toward a more plate-like structure, and increased cortical bone thickness. These changes in cancellous and cortical bone morphology should improve biomechanical competence and are consistent with the substantially reduced incidences of vertebral and nonvertebral fractures during administration of teriparatide. J Bone Miner Res 2003;18:1932-1941

The Clinical Global Impression-Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia.

Abstract: Objective: To describe the development and validation of the Clinical Global Impression–Schizophrenia (CGI-SCH) scale, designed to assess positive, negative, depressive and cognitive symptoms in schizophrenia. Method: The CGI-SCH scale was adapted from the CGI scale. Concurrent validity and sensitivity to change were assessed by comparison with the Positive and Negative Symptom Severity (PANSS) and Global Assessment of Functioning (GAF) scales. To evaluate inter-rater reliability, all patients were assessed by two clinicians. Results: Symptoms were assessed in 114 patients. Correlation coefficients between the CGI-SCH and the GAF and PANSS scores were high (most above 0.75), and were highest for positive and negative symptoms. Reliability was substantial (intraclass correlation coefficient, ICC > 0.70) in all but one dimension (depressive dimension, ICC = 0.64). Conclusion: The CGI-SCH scale is a valid, reliable instrument to evaluate severity and treatment response in schizophrenia. Given its simplicity, brevity and clinical face validity, the scale is appropriate for use in observational studies and routine clinical practice.

Brain to Plasma Amyloid-β Efflux: a Measure of Brain Amyloid Burden in a Mouse Model of Alzheimer's Disease

Abstract: The deposition of amyloid-β (Aβ) peptides into amyloid plaques precedes the cognitive dysfunction of Alzheimer's disease (AD) by years. Biomarkers indicative of brain amyloid burden could be useful for identifying individuals at high risk for developing AD. As in AD in humans, baseline plasma Aβ levels in a transgenic mouse model of AD did not correlate with brain amyloid burden. However, after peripheral administration of a monoclonal antibody to Aβ (m266), we observed a rapid increase in plasma Aβ and the magnitude of this increase was highly correlated with amyloid burden in the hippocampus and cortex. This method may be useful for quantifying brain amyloid burden in patients at risk for or those who have been diagnosed with AD.