A phase II trial of the vitamin D analogue Seocalcitol (EB1089) in patients with inoperable pancreatic cancer

Inoperable cancer of the exocrine pancreas responds poorly to most conventional anti-cancer agents, and new agents are required to palliate this disease. Seocalcitol (EB1089), a vitamin D analogue, can inhibit growth, induce differentiation and induce apoptosis of cancer cell lines in vitro and can also inhibit growth of pancreatic cancer xenografts in vivo. Thirty-six patients with advanced pancreatic cancer received once daily oral treatment with seocalcitol with dose escalation every 2 weeks until hypercalcaemia occurred, following which patients continued with maintenance therapy. The most frequent toxicity was the anticipated dose-dependent hypercalcaemia, with most patients tolerating a dose of 10–15 μg per day in chronic administration. Fourteen patients completed at least 8 weeks of treatment and were evaluable for efficacy, whereas 22 patients were withdrawn prior to completing 8 weeks' treatment and in 20 of these patients withdrawal was due to clinical deterioration as a result of disease progression. No objective responses were observed, with five of 14 patients having stable disease in whom the duration of stable disease was 82–532 days (median=168 days). The time to treatment failure (n=36) ranged from 22 to 847 days, and with a median survival of approximately 100 days. Seocalcitol is well tolerated in pancreatic cancer but has no objective anti-tumour activity in advanced disease. Further studies are necessary to determine if this agent has any cytostatic activity in this malignancy in minimal disease states

Presence and binding characteristics of calcitriol receptors in human fetal gut

AbstractIn the present study, we show for the first time the presence of calcitriol-specific binding sites in hypertonic extracts of cells isolated from human fetal small intestine and colon from 13–21 weeks of gestation. Woolf plot analysis of the binding characteristics revealed the presence of a single class of high affinity receptors. The presence of specific receptors for calcitriol in fetal intestine and colon opens interesting possibilities as to the role of this hormone in human gut development

Abstract 14888: Extracellular Matrix Quantification of Fully Regenerated Neochorade After Bio-scaffold Mitral Valve Implantation in a Juvenile Non-human Primate Model

Introduction: To investigate enhanced treatment options for critical mitral valve disease in children, we implanted a bio-scaffold mitral valve comprising of porcine small intestinal submucosa (PSIS) in a juvenile baboon model. Hypothesis: New tissue formation would be accelerated at physical connections between the replacement bio-scaffold valve and native cardiac tissues, due to direct extracellular matrix (ECM) communications. Methods: Juvenile baboons (n=2) were implanted with a hand-made bicuspid PSIS (Cormatrix, Roswell, GA) mitral valve. The PSIS valves were excised at 11- and 20-months post-implantation. Images of histological stains (Movat’s Pentachrome; Alizée Pathology, Inc., Thurmont, MD) were subsequently spatially mapped for ECM quantification (MATLAB; Mathworks, Natick, MA). Results: PSIS bio-scaffold mitral valves (11- and 20-months post-implantation) facilitated complete regeneration of neochordae. The neochordae seamlessly integrated into the papillary muscles and left ventricular insertion sites ( Figure 1A, E ). We also found that with an increase in implantation duration of ~ 9 months, the collagen, proteoglycan and elastin content (per mm 2 ; Figure 1B-D, F-H ) had a fold-change of 6.96, 18.42 and 4.94, respectively. Conclusions: Our findings suggest that the PSIS bio-scaffold mitral valve apparatus can regenerate neochordae without the need for any biochemical or biomechanical treatment. Nonetheless, other valve spatial areas of importance (e.g. leaflets) will require additional strategies. As a next step, we will produce oscillatory flow-conditioned, stem cell-derived ECM, to accelerate tissue regeneration. The mechanical parameters that we computed to permit physiological oscillatory flow conditions are an oscillatory shear index (OSI) of 0.23 and time averaged bio-scaffold shear stress (TAB-SSS) of 4.6 dynes/cm 2 . Acknowledgements: AHA Award ID: 16GRNT31090009; The Miami Research Heart Institute; FIU-UGS DYF. </jats:p