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Introduction: Basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) are important positive regulators of tumor growth and angiogenesis. This study was designed to assess the effect of bFGF and HGF infusion on tumor growth and metastases in a syngeneic, rat colon adenocarcinoma tumor model. Methods: Liver tumors were established in each of 21 BD9 rats via surgical, subcapsular implantation of a 1.0 mm3 piece of a subcutaneously grown DHD/K12/TRb tumor. Test groups were infused systemically with 5 μg/day/rat bFGF or 0.5 μg/day/rat HGF via osmotic pump; and controls received saline. At 28 days all animals were killed and examined. Tumor volume was calculated as π[a2 × b]/6, where a is shorter length and b the longer length. Liver and lung specimens were fixed in zinc formalin and embedded in paraffin for H&E staining and immunohistochemical study. Results: On histologic examination, tumor cells were seen to grow along blood vessel branches after infusion bFGF and HGF. Both VEGF and Flk-1 expression was strong cytoplasmic staining in cancer cells from hepatic, peritoneal and lung metastases. Conclusion: While both bFGF and HGF appear to induce an increase in tumor growth in this model, the effect of bFGF was marked. Similarly, HGF appeared to stimulate the development of distant metastases, though not reaching significance, while bFGF produced local and distant metastases with statistically significant increase in lung metastases. This rat colon adenocarcinoma cell line expressed VEGF and its receptor Flk-1. Further studies are required to evaluate the mechanism of tumor growth and metastasis stimulation. TABLE—ABSTRACT P8Control (n = 7)bFGF (n = 7)HGF (n = 6&ast;)P valueTumor volume (mm3)48.8 ± 17.685.1 ± 25.0†59.3 ± 26.9†<.05Intrahepatic mets03/7‡0‡=.19Peritoneal mets03/7‡1/6‡=.19Lung mets&ast;&ast;05/7‡1/6‡=.02&ast;One rat in this group died at postoperative two weeks.†,‡bFGF group vs control group by Kruskal Wallis test. [Copyright &y& Elsevier]

Abstract Objective Concerns exist over hypertyrosinaemia that is observed following treatment with nitisinone. It has been suggested that tyrosine may compete with tryptophan for uptake into the central nervous system, and or inhibit tryptophan hydroxylase activity reducing serotonin production. At the National Alkaptonuria (AKU) Centre nitisinone is being used off-licence to treat AKU, and there is uncertainty over whether hypertyrosinaemia may alter mood. Herein results from clinical and biochemical assessments of depression in patients with AKU before and after treatment with nitisinone are presented. Patients and methods 63 patients were included pre-nitisinone treatment, of these 39 and 32 patients were followed up 12 and 24 months after treatment. All patients had Becks Depression Inventory-II (BDI-II) assessments (scores can range from 0 to 63, the higher the score the more severe the category of depression), and where possible urinary monoamine neurotransmitter metabolites and serum aromatic amino acids were measured as biochemical markers of depression. Results Mean (±standard deviation) BDI-II scores pre-nitisinone, and after 12 and 24 months were 10.1(9.6); 9.8(10.0) and 10.5(9.9) (p ≥ 0.05, all visits). Paired scores (n = 32), showed a significant increase at 24 months compared to baseline 10.5(9.9) vs. 8.6 (7.8) (p = 0.03). Serum tyrosine increased at least 6-fold following nitisinone (p ≤ 0.0001, all visits), and urinary 3-methoxytyramine (3-MT) increased at 12 and 24 months (p ≤ 0.0001), and 5-hydroxyindole acetic acid (5-HIAA) decreased at 12 months (p = 0.03). Conclusions BDI-II scores were significantly higher following 24 months of nitisinone therapy in patients that were followed up, however the majority of these patients remained in the minimal category of depression. Serum tyrosine and urinary 3-MT increased significantly following treatment with nitisinone. In contrast urinary 5-HIAA did not decrease consistently over the same period studied. Together these findings suggest nitisinone does not cause depression despite some observed effects on monoamine neurotransmitter metabolism. [ABSTRACT FROM AUTHOR]