Current trends in transplantation and immunosuppressive treatment

The American Society of Transplant Surgeons and the American Society of Transplantation jointly sponsored their third American Transplant Congress on May 30-June 4, 2003. The meeting, which took place in Washington, D.C., U.S.A., thoroughly reviewed the different immunosuppressive protocols for every kind of transplantation. Also presented were the immunological and nonimmunological factors influencing the success or failure of transplants from the point of view of genetics, the place of new investigative agents and the current status of various therapeutic protocols intended to induce tolerance or normal function of grafts in the absence of immunosuppressive treatment. Presentations on renal, liver, heart, lung, multivisceral and islet transplantation are covered in this report, as well as aspects of new immunosuppressive agents, genomics in transplantation and tolerance induction in allotransplantation.     

Surgical outcome in 85 patients with primary cardiac tumors

BACKGROUND: We present a large, single institution experience with adult cardiac tumors and address factors affecting outcome. METHODS: A retrospective review was made of all patients who underwent surgery for primary cardiac tumors from April 1975 through August 2002. RESULTS: Eighty-five patients (33 male and 52 female) with a mean age of 54 years were identified with follow-up available for 80 (94%) patients. There were 68 (80%) benign tumors and 17 (20%) malignant tumors. Three tumors recurred and were resected giving a total of 88 surgeries. All benign tumors were grossly resected and the extent of resection for malignant disease ranged from 14 (78%) gross resections and 3 (17%) debulkings to 1 (5%) biopsy. There were 4 (5%) early hospital deaths. Median survival was 9.6 months and 322 months for patients with malignant and benign diseases, respectively. Significant predictors of long-term mortality were malignant disease (P <0.0001) and New York Heart Association class (P <0.03). CONCLUSIONS: Surgical resection provides excellent outcome in patients with benign cardiac tumors. Malignant tumors continue to pose a challenge with good local tumor control but limited survival owing to metastatic disease.     

Cancer incidence among 10,211 airline pilots: a Nordic study

BACKGROUND: Commercial airline pilots are exposed to cosmic radiation and other potentially carcinogenic elements during work and leisure activities. HYPOTHESIS: Work-related factors affect cancer pattern of the pilots. METHODS: A cohort of 10,051 male and 160 female airline pilots from Denmark, Finland, Iceland, Norway, and Sweden was followed for cancer incidence through the national cancer registries. There were 177,000 person-years at follow-up, 51,000 of them accumulated after 20 yr since the time of first employment. Standardized incidence ratios (SIRs) were defined as ratios of observed over expected numbers of cases based on national cancer incidence rates. Dose-response analyses were done with Poisson regression method. RESULTS: Among male pilots, there were 466 cases of cancer diagnosed vs. 456 expected. The only significantly increased SIRs concerned skin cancer: melanoma 2.3 (95% CI 1.7-3.0), squamous cell cancer 2.1 (1.7-2.8), and basal cell carcinoma 2.5 (1.9-3.2). The relative risk of skin cancers increased with the time since first employment, the number of flight hours, and the estimated radiation dose. There was an increase in the relative risk of prostate cancer with increasing number of flight hours in long-distance aircraft (p trend 0.01). No increased incidence was found for acute myeloid leukemia or brain cancer which were of interest a priori based on earlier studies. CONCLUSIONS: This large study, based on reliable cancer incidence data, showed an increased incidence of skin cancer. It did not indicate a marked increase in cancer risk attributable to cosmic radiation although some influence of cosmic radiation on skin cancer cannot be entirely excluded.     

Cell surface association of matrix metalloproteinase-9 (gelatinase B)

Matrix metalloproteinase (MMP)-9 (gelatinase B) belongs to the MMP family of zinc-dependent endopeptidases that has been associated with tumor cell invasion and metastasis and tumor-induced angiogenesis. As a secreted MMP, pro-MMP-9 is released into the extracellular environment by both tumor and stroma cells, where it fulfills its proteolytic functions degrading both extracellular matrix (ECM) and non-ECM proteins. A major dilemma in our understanding of MMP-9 function is how the released protease is targeted to the right location and how its activity is controlled at the pericellular space. It has been proposed that MMP-9 interact with cell surface components and that this type of interaction positively regulates enzymatic activation and activity. However, recent evidence shows that association of MMP-9 with the cell surface is mediated by a distinct array of surface proteins that serve to regulate multiple aspects of the enzyme function including localization, inhibition and internalization. How these distinct mechanisms regulate the overall MMP-9 activity at the pericellular space remains an important goal in our understanding of MMP-9 function at the cell surface. Furthermore, the study of surface-associated MMP-9 imposes new conceptual and methodological challenges with particular consideration to the unique structural and functional characteristics of this key enzyme.     

Stromal cell-derived factor 1alpha stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and Akt

In this paper, we describe the role of chemokine receptor CXCR4 activation by its natural ligand, the chemokine stromal cell-derived factor (SDF-1) (CXCL12), in glioblastoma cell growth in vitro. We show that both CXC chemokine receptor 4 (CXCR4) and SDF-1 mRNA are expressed in several human glioblastoma multiforme tumor tissues and in two human glioblastoma cell lines, U87-MG and DBTRG-05MG. These cells are able to secrete SDF-1 under basal conditions, and the rate of secretion is highly increased after lipopolysaccharide or 1% fetal bovine serum treatment. Exogenous SDF-1alpha induces proliferation in a dose-dependent manner in both cell lines. Moreover, we observed that SDF-1alpha-dependent proliferation is correlated with phosphorylation and activation of both extracellular signal-regulated kinases 1/2 and Akt and that these kinases are independently involved in glioblastoma cell proliferation. The role of CXCR4 stimulation in glioblastoma cell growth is further demonstrated by the ability of human monoclonal CXCR4 antibody (clone 12G5) to inhibit the SDF-1alpha-induced proliferation as well as the proliferation induced by SDF-1-releasing treatments (lipopolysaccharide and 1% fetal bovine serum). These data support a role for SDF-1alpha in the regulation of glioblastoma growth in vitro, likely through an autocrine/paracrine mechanism.