Prognostic classification in myelodysplastic syndromes

Factors for predicting the prognosis of myelodysplastic syndromes (MDS) have been widely used over the last few years. The proportion of bone marrow blasts, number and severity of cytopenias, and cytogenetic abnormalities are the main prognostic factors and can be used in combination to determine prognostic scores capable of predicting the outcome with fairly high accuracy. Molecular biology parameters, such as RAS and p53 mutations, can also be of assistance in establishing a prognosis. Factors that predict responsiveness to therapy are usually the same as those that predict survival. Current prognostic scores are unable to identify the minority of patients who will have very long survivals and therefore require no treatment.     

Neomycin inhibits angiogenin-induced angiogenesis

A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy.     

Regulation of the function of P-glycoprotein by epidermal growth factor through phospholipase C

Many multidrug-resistant (MDR) cell lines overexpress the epidermal growth factor receptor (EGFR) as well as P-glycoprotein (P-gp). However, the role of the increased EGFR in P-gp-mediated drug resistance remains unclear. Since recent studies suggest that activation of phospholipase C (PLC) could increase the phosphorylation of P-gp, and activation of the EGFR would also activate PLC, we investigated whether the effect of epidermal growth factor (EGF) on the phosphorylation of P-gp was mediated through PLC. Treatment of the human MDR breast cancer cell line, MCF-7/AdrR, with EGF increased the phosphorylation of P-gp by 20-50%. The increased phosphorylation of P-gp was accompanied by stimulation of PLC activity, as measured by the production of inositol, 1,4,5-trisphosphate and diacylglycerol, products of phosphatidylinositol-4,5-bisphosphate hydrolysis. Treatment of MDR cells with EGF also had detectable effects on P-gp function. For example, following incubation of MCF-7/AdrR cells with ECF, we observed a consistent decrease in total vinblastine (VBL) accumulation. Kinetic analysis revealed this change to be due to an increase in membrane efflux. The latter was measured by the initial uptake velocity, which was inhibited by EGF. VBL uptake measured at 0-320 sec was inhibited by 20-40%, which was associated with a similar increase in VBL efflux. EGF had no effect on drug accumulation, uptake, or efflux in sensitive MCF-7 cells. These data indicate that EGF can modulate the phosphorylation and function of P-gp, and suggest that this effect may be initiated by the activation of PLC.     

Triphasic spiral computerized tomography of the liver: vascular models of non-cystic focal lesions

PURPOSE: The purpose of this study was to investigate if Triphasic Spiral CT (arterial, portal and equilibrium phases) can improve the characterization of noncystic focal lesions. MATERIAL AND METHODS: Sixty-six patients with suspected focal liver disease underwent Triphasic Spiral CT. After the injection of 120-140 ml contrast material at 3 ml/s the liver was imaged in the arterial (scanning delay: 20-27 s), portal (scanning delay: 45-80 s) and equilibrium (scanning delay: 5-8 min) phases. The enhancement of each lesion was evaluated in each phase and the lesions were grouped by enhancement pattern (11 patterns in all). The reference standards in our 66 patients were surgery (12), biopsy (43), MRI (9), follow-up (9), somatostatin receptor scintigraphy (6). RESULTS: One hundred and twenty-six liver lesions were detected in 66 patients, four of 11 enhancement patterns (hypo/hyper/hyper, hyper/iso/iso, hyper/hyper/iso, hyper/hyper/hyper) were always referrable to benign disease (hemangioma, focal nodular hyperplasia-FNH-adenoma). Four of 11 enhancement patterns (iso/hypo/hypo, iso/iso/hypo, hyper/hypo/hypo, hyper/hyper/hypo) were always referrable to malignant disease (hepatocellular carcinoma-HCC-metastases). The other two patterns (hypo/hypo/hypo, hypo/hypo/hyper) were seen in both benign and malignant diseases. CONCLUSIONS: Triphasic Spiral CT improves the characterization of HCC, FNH, adenoma and hemangioma. The arterial and the equilibrium phases add no information to the yield of the portal venous phase in metastases, except for those from pancreas neuroendocrine tumors in the arterial phase. In our experience, patients with unclassified lesions at US or conventional CT, suspected HCC and metastases from pancreas neuroendocrine tumors should be submitted to Triphasic CT of the liver. This technique however does not appear to be indicated in the study of liver metastases from hypovascular tumors, while it improves the detection of FNH and adenoma.     

Merkel cell tumor. Report of case and treatment with octreotide

Merkel cell carcinoma is a rare neuroendocrine tumor of the skin. Prognosis is very poor particularly when systemic disease is present. Surgery, chemo and/or radiotherapy treatment are not able to guarantee long survival and quality of life is also very poor. We know that neuroendocrine tumor can be in possession of receptors for somatostatin; during the past years, these receptors have been demonstrated in vivo by octreoscan. We report a case of a patient suffering from metastatic Merkel cell carcinoma; because he was elderly, neither chemotherapy nor radiotherapy were possible as a consequence of the explosion of the disease after surgery. The presence of receptors for somatostatin analogues (octreoscan) allowed treatment with octreotide causing the immediate disappearance of metastasis. After ten months of treatment the patient presents a complete remission of disease. Octreotide, the most important somatostatin analogue, represents a primary role in the neuroendocrine tumor management; the drug also lacks of toxicity.     

Influence of bile on beta-galactosidase activity and cell viability of Lactobacillus reuteri when subjected to freeze-drying

The effect of bile on beta-galactosidase activity and cell viability was investigated using two strains of Lactobacillus reuteri that were subjected to freeze-drying. In the presence of 0.15% oxgall, beta-galactosidase activity of the whole cells was significantly increased. After lyophilization, the cultures that had been treated with oxgall showed a low survival rate without changes in beta-galactosidase activity. The poor resistance of the cells to damage from freeze-drying might be related to the presence of membranous structures containing simple folds and buds of the cell membrane, as was observed by transmission electron microscopy.