The haematogenous phase of cancer metastasis facilitates the transport of metastatic cells within the blood and incorporates a sequence of interactions between circulating intravascular cancer cells and the endothelium of blood vessels at the sites of tumour cell arrest. Initial interactions involve mechanical contact and transient adhesion, mediated by endothelial selectins and their ligands on the neoplastic cells. This contact initiates a sequence of activation pathways that involves cytokines, growth factors, bioactive lipids, and reactive oxygen species produced by either the cancer cell or the endothelium. These molecules elicit expression of integrin adhesion molecules in cancer cells and the endothelium, matrix metalloproteinases, and chemotactic factors that promote the attachment of tumour cells to the vessel wall and/or transvascular penetration. Induction of endothelial free radicals can be cytotoxic to cancer cells. Collectively, the sum of these interactions constitutes an interdependent relationship, the outcome of which determines the fate of the metastatic process. Copyright © 2000 John Wiley & Sons, Ltd.

Background: Cancer patients are increasingly seeking out complementary and alternative medicine (CAM) and might be reluctant to disclose its use to their oncology treatment team. Often, CAM agents are not well studied, and little is known about their potential interactions with chemotherapy, radiation therapy, or biologic therapies, and their correlations with outcomes. In the present study, we set out to determine the rate of CAM use in patients receiving treatment at a Northern Ontario cancer centre. Methods: Patients reporting for treatment at the Northeast Cancer Centre (NECC) in Sudbury, Ontario, were asked to complete an anonymous questionnaire to assess CAM use. Changes in CAM use before, compared with after, diagnosis were also assessed. Results: Patients in Northern Ontario reported significant CAM use both before and after diagnosis. However, as a function of the CAM type, CAM use was greatly enhanced after cancer diagnosis. For example, the number of patients who reported use of biologic products increased to 51.8% after a cancer diagnosis from 15.6% before a cancer diagnosis. Patients reported much smaller changes in the use of alternative medical systems or spiritual therapy after diagnosis. Vitamin use was reported by 66% of respondents, and the number of different CAMS used correlated significantly with the reported number of vitamins used. Conclusions: Use of CAM, particularly biologic products, increased significantly after a cancer diagnosis. Further studies are required to examine the effect of CAM use on the efficacy and safety of cancer therapies.

Pseudomonas aeruginosa is inherently resistant to most conventional antibiotics. The mechanism of resistance of this bacterium is mainly associated with the low permeability of its outer membrane to these agents. We sought to assess the bactericidal efficacy of liposome-entrapped aminoglycosides against resistant clinical strains of P. aeruginosa and to define the mechanism of liposome-bacterium interactions. Aminoglycosides were incorporated into liposomes, and the bactericidal efficacies of both free and liposomal drugs were evaluated. To define the mechanism of liposome-bacterium interactions, transmission electron microscopy (TEM), flow cytometry, lipid mixing assay, and immunocytochemistry were employed. Encapsulation of aminoglycosides into liposomes significantly increased their antibacterial activity against the resistant strains used in this study (MICs of ≥32 versus ≤8 μg/ml). TEM observations showed that liposomes interact intimately with the outer membrane of P. aeruginosa , leading to the membrane deformation. The flow cytometry and lipid mixing assays confirmed liposome-bacterial membrane fusion, which increased as a function of incubation time. The maximum fusion rate was 54.3% ± 1.5% for an antibiotic-sensitive strain of P. aeruginosa and 57.8% ± 1.9% for a drug-resistant strain. The fusion between liposomes and P. aeruginosa significantly enhanced the antibiotics' penetration into the bacterial cells (3.2 ± 2.3 versus 24.2 ± 6.2 gold particles/bacterium, P ≤ 0.001). Our data suggest that liposome-entrapped antibiotics could successfully resolve infections caused by antibiotic-resistant P. aeruginosa through an enhanced mechanism of drug entry into the bacterial cells.

Monocytes are major targets of HIV infection in patients with AIDS. In vitro infection of monocytes with HIV is associated with increased expression of β 2 integrins, which increases both monocyte aggregation and monocyte/endothelial adhesion as well as monocyte metalloproteinase (MMP-9) expression. Treatment of primary monocytes with soluble HIV-Tat protein mimicked many of the properties of HIV infection of monocytes. Tat treatment up-regulated the expression of the β 2 integrins, which was associated with the formation of large aggregates of monocytes and increased adhesion to endothelial monolayers. Treatment of monocytes with Tat increased their adhesion to both untreated and TNF-α-treated endothelial monolayers, and adhesion was inhibited by inclusion of anti-β 2 and anti-ICAM-1 Abs. The increased adhesion of activated monocytes was accompanied by substantial disruption of the endothelial monolayers, with retraction or detachment of individual endothelial cells. Tat treatment of monocytes up-regulated the synthesis and release of the protease MMP-9, providing a potential mechanism to explain endothelial cell/basement membrane detachment. Thus, extracellular Tat is capable of activating monocytes even in the absence of HIV infection. Our studies demonstrate that many of the effects of HIV infection on monocyte homotypic and heterotypic adhesion, protease secretion, and disruption of the endothelium can be mimicked by treatment with HIV-Tat protein alone. These results suggest a mechanism where monocytes could be inappropriately activated by HIV-Tat, secreted by HIV-infected cells, causing them to extravasate into underlying tissues and ultimately contribute to tissue damage as seen during the progression of AIDS.