The use of immunotoxins (ITs) in the therapy of cancer, graft-vs-host disease (GvHD), autoimmune diseases, and AIDS has been ongoing for the past two decades. ITs contain a targeting moiety for delivery and a toxic moiety for cytotoxicity. Theoretically, one molecule of a toxin, routed to the appropriate cellular compartment, will be lethal to a cell. Newly developed MoAbs, toxins, and molecular biological technologies have enabled researchers to construct ITs that can effectively kill many different cell types. In fact, phase I/II clinical trials have given promising results. Although nonspecific toxicity and immunogenicity still limit the use of IT therapy, these agents hold enormous promise in an optimal setting to treat minimal disease.

HER-2/neu is overexpressed on a variety of human adenocarcinomas and overexpression has been associated with a poor prognosis. For this reason, HER-2 has become an attractive target for immunotherapy. To facilitate testing of anti-HER-2-monoclonal antibodies (MAbs) and immunotoxins (ITs), we have evaluated the in vivo growth and metastatic spread of three HER-2-overexpressing human breast cancer cell lines (BT474, MDA-MB-453 and HCC1954) and one ovarian cancer cell line (SKOV3.ip1) in pre-irradiated male SCID mice using subcutaneous (s.c.), intravenous (i.v.) and intraperitoneal (i.p.) routes of injection. All the cell lines tested grew as s.c. tumors and the growth of BT474 and MDA-MB-453 cells after s.c. injection was improved by co-inoculation with Matrigel. Metastases to the lungs were detectable by PCR or histopathology after s.c. injection of BT474 and to a much lesser extent after s.c. injection of HCC1954, MD-MB-453 and SKOV3.ip1 cells. I.p. injection of HCC1954 and SKOV3.ip1 cells produced fatal ascites while i.v. injection of SKOV3.ip1, but not BT474 or MDA-MB-453 cells, resulted in infiltration of lungs and death within 9-11 weeks.

SummaryAim:The aim of this study was to explore associations between abdominal obesity, inflammatory markers, and subclinical organ damage in 740 patients with type 2 diabetes. Methods:Waist circumference (WC) and sagittal abdominal diameter (SAD) was measured. Blood samples were analyzed for; C-reactive protein (CRP) and IL-6. Carotid intima-media thickness (IMT) was evaluated by ultrasonography. Aortic pulse wave velocity (PWV) was measured with applanation tonometry. Results:Abdominal obesity measured as SAD and WC were significantly correlated with; IL-6 (WC r=0.27, p<0.001, SAD r=031, p<0.001 ), CRP (WC r=0,29, p <0.001, SAD r=0,29, p <0.001), IMT (WC r=0.09 p=0.013, SAD r=0.11, p=0.003) and PWV (WC r=0.18, p<0.001, SAD r=0.21, p <0.001). In multiple linear regressions with IMT or PWV as dependent variable and age, sex, statins, systolic blood pressure (SBP), Body Mass Index (BMI), CRP and HbA1c, as independent variables, both SAD and WC, remained associated with IMT and PWV. In stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV. Conclusion:We conclude that SAD and WC are feasible measures of obesity that provides information on inflammation, atherosclerosis and arterial stiffness in type 2 diabetes. However, SAD was slightly more robustly associated to subclinical organ damage, compared with WC.