PubMed · 6316428
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M J Varas Lorenzo. 1983. [Glucagonomas].. https://pubmed.ncbi.nlm.nih.gov/6316428/
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The Eph family of receptor tyrosine kinases and their ligands, known as ephrins, play a crucial role in vascular development during embryogenesis. The function of these molecules in adult angiogenesis has not been well characterized. Here, we report that blocking Eph A class receptor activation inhibits angiogenesis in two independent tumor types, the RIP-Tag transgenic model of angiogenesis-dependent pancreatic islet cell carcinoma and the 4T1 model of metastatic mammary adenocarcinoma. Ephrin-A1 ligand was expressed in both tumor and endothelial cells, and EphA2 receptor was localized primarily in tumor-associated vascular endothelial cells. Soluble EphA2-Fc or EphA3-Fc receptors inhibited tumor angiogenesis in cutaneous window assays, and tumor growth in vivo. EphA2-Fc or EphA3-Fc treatment resulted in decreased tumor vascular density, tumor volume, and cell proliferation, but increased cell apoptosis. However, EphA2-Fc had no direct effect on tumor cell growth or apoptosis in culture, yet inhibited migration of endothelial cells in response to tumor cells, suggesting that the soluble receptor inhibited blood vessel recruitment by the tumor. These data provide the first functional evidence for Eph A class receptor regulation of pathogenic angiogenesis induced by tumors and support the function of A class Eph receptors in tumor progression.
Pancreaticoduodenectomy (PD) has been performed infrequently for islet cell tumors of the pancreas because of the perceived perioperative morbidity and the relatively protracted natural history of those tumors. To determine whether the improved safety of PD affects long-term outcome of patients with islet cell tumors, we reviewed our experience. All consecutive patients who underwent PD or total pancreatectomy for islet cell tumors between 1980 and 1995 were analyzed. Diagnoses were based on histologic findings and endocrine (biochemical) manifestations of the tumors. Patients were followed by outpatient clinic visits and mail correspondence. Clinical and pathologic factors were analyzed for prognostic risk. Survival and recurrence curves were generated using the Kaplan-Meier method, and the log-rank test was used for comparison (p <0.05 was significant). We identified 29 patients who fulfilled the inclusion criteria with an even distribution by gender (14M:15F). Mean age of patients was 56 years (SD +/- 14 years); mean tumor size was 4.4 cm (SD +/- 2.6 cm). Most tumors were nonfunctioning (n = 20); there were 4 somatostatinomas, 3 insulinomas, and 2 gastrinomas. Operating time was 316 minutes (SD +/- 75 minutes), median transfusion requirement was 0 units (mean 1.5 units). Standard Whipple resection was performed in 20 patients; the pylorus-preserving Whipple procedure, in 7; and total pancreatectomy, in 2. Regional lymph nodes were involved by tumor in 16 patients. The complication rate was 31%, and operative mortality was 10% (n = 3). Length of hospital stay was 17 days (SD +/- 8.8 days). Overall survival was 81% and 70% at 5 and 10 years. Recurrence-free survival was 76% at 5 and 10 years. There was a trend toward greater recurrence-free survival for node-negative patients (88% vs 65% at 5 years, p = 0.13), and overall survival was greater for node-negative patients (100% vs 67% at 5 years, p = 0.04). Mean follow-up was 8.8 years. PD is an appropriate strategy for selected malignant islet cell tumors of the pancreas, which offers extended survival with a low recurrence rate and control of endocrine symptoms.
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