Targeting Cancer Stem Cells to Modulate Alternative Vascularization Mechanisms

Recently, many papers have shown that tumor vascularization can be explained by angiogenesis, recruitment, cooption, vasculogenic mimicry and by mosaic vessels. In particular, vasculogenic mimicry seems to be different from mosaic blood vessels, where tumor cells form a part of the surface of the vessel while the remaining part is covered by endothelium. In this case, tumor cells in apparent contact with the lumen do not show an endothelial phenotype. More recently, vasculogenic mimicry was proposed to occur in patients with multiple myeloma due to bone marrow macrophages. Herein, all these data are, for the first time, discussed critically in comparison to cancer stem cells-which show high trans-differentiative capacity-and bone-marrow derived stem cells. In fact, the presence of alternative vasculogenic patterns might be due to the presence of stem cell population (cancer stem cells or bone-marrow stem cells). In this connection, the literature is discussed extensively and possible models are proposed. Pharmacological perspectives will also discuss.     

Patient discomfort during screen-film mammography

Vigorous compression is required to minimize radiation dose and maximize image quality for screen-film mammography. Of 356 women who adequately completed a questionnaire following mammography, 171 (48%) reported mammography to be comfortable, 135 (38%) uncomfortable but tolerable, 39 (11%) very uncomfortable, and only 11 (3%) found the examination to be intolerable. Only 14 women (4%) indicated that they would not return for mammography at our facility in the future. Because of this high level of acceptance of compression by women, technologists and radiologists should not hesitate to use vigorous compression to optimize image quality and decrease radiation dose to the patient.     

Aluminium Mobilization Following Renal Transplantation and the Possible Effect on Susceptibility to Bacterial Sepsis

We monitored urinary aluminium excretion in 60 renal allograftrecipients for the first 6 months following transplantation.Plasma and urinary aluminium values steadily decreased duringthe study period. Patients who suffered two or more bacterialinfections during this period excreted more urinary aluminiumthan those with only one or no infections. Twenty patients experienced a two-fold or greater sudden unexpectedincrease in urinary aluminium excretion; 14 of these patients(60 per cent) had evidence of infection (10 bacterial and fourviral), at this time. Both urinary aluminium and fractionalaluminium excretion were greater in the 10 patients with bacterialinfection than in the other 10 patients. Thus, patients who suffered bacterial infections had higherbase-line urinary aluminium excretion, suggesting a higher bodyburden of aluminium. In addition, bacterial sepsis was associatedwith aluminium release from tissue stores with an associatedincrease in urinary aluminium excretion. This implies that patientswith an increased body burden of aluminium are more prone tobacterial sepsis, and that aluminium excretion is increasedduring sepsis.     

Interleukin-1α and tumour necrosis factor-α modulate the production of monocyte chemoattractant protein-1 by cultured human glomerular visceral epithelial cells

Summary: Mediators released by glomerular macrophages may stimulate glomerular visceral epithelial cells (GVEC) to produce cytokines, growth factors or extracellular matrix components. This study describes that human GVEC produce monocyte chemoattractant protein-1 (MCP-1), a monocyte-specific chemotactic factor, and the effects of interleukin-lα (IL-1α) and tumour necrosis factor-α (TNF-a) on the production of MCP-1 by GVEC.
We observed that the intensity of MCP-1 staining in GVEC is stronger in membranous nephropathy and glomerulosclerosis than in normal kidneys. Various cell lines of GVEC produced significant amounts of MCP-1, as assessed by inhibition radio-immunoassay. the presence of IL-1α and TNF-α during culture of GVEC enhanced the production of MCP-1 in a dose- and time-dependent manner. Glomerular visceral epithelial cells in culture express mRNA for MCP-1 and the expression is upregulated 2.0- and 1.4-fold in the presence of optimal concentration of IL-1α and TNF-α, respectively. De novo synthesis of MCP-1 is supported by the observation that MCP-1 production is fully inhibited by cydoheximide. Monocyte chemoattractant protein-1 isolated from GVEC supernatants exhibits a molecular size of 12 and 10 kDa as determined by gel filtration chromatography. Both sizes of MCP-1 is chemotactically active for monocytes.
This study shows increased MCP-1 production by cultured human GVEC after stimulation with the inflammatory cytokines IL-1α and TNF-α. the expression of MCP-1 in GVEC was found to be upregulated in membranous nephropathy and glomerulosclerosis. These findings suggest that MCP-1 may be involved in glomerular injury in these diseases. the possible role of MCP-1 in the pathogenesis of human glomerulonephritis is discussed.     

Pharmacokinetics of cyclophosphamide in patients with systemic necrotizing angiitis

Summary— Cyclophosphamide pharmacokinetics were investigated following administration to patients with systemic necrotizing angiitis. Ten patients (eight women and two men) received cyclophosphamide as a 1-h-rate-constant intravenous infusion at doses ranging from 600 to 1200 mg. All patients received concomitant oral prednisone (1 mg/kg/d). Blood samples were collected at the end of drug infusion and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h later. Serum cyclophosphamide concentrations were assayed by high pressure liquid chromatography. The peak serum cyclophosphamide levels ranged from 15.7 to 29.4 mg/L. The mean cyclophosphamide elimination half-life was 6.2 ± 1.3 h (mean ± SD). The mean apparent volume of distribution and mean total plasma clearance were, respectively, 0.75 ± 0.22 L/kg (mean ± SD) and 83 ± 22 mL/min (mean ± SD). These results obtained in systemic vasculitic diseases were consistent with those observed in other studies with cancer patients receiving comparable doses of cyclophosphamide.