Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment

The tumor microenvironment consists of tumor, immune, stromal, and inflammatory cells which produce cytokines, growth factors, and adhesion molecules that promote tumor progression and metastasis. Of particular interest in this setting is interleukin-1 (IL-1), a pleiotropic cytokine with numerous roles in both physiological and pathological states. It is known to be up regulated in many tumor types and has been implicated as a factor in tumor progression via the expression of metastatic and angiogenic genes and growth factors. A number of studies have reported that high IL-1 concentrations within the tumor microenvironment are associated with a more virulent tumor phenotype. Solid tumors in which IL-1 has been shown to be up regulated include breast, colon, lung, head and neck cancers, and melanomas, and patients with IL-1 producing tumors have generally bad prognoses. The exact mechanisms by which IL-1 promotes tumor growth remain unclear, though the protein is believed to act via induction of pro-metastatic genes such as matrix metalloproteinases and through the stimulation of adjacent cells to produce angiogenic proteins and growth factors such as VEGF, IL-8, IL-6, TNFα, and TGFβ. The IL-1 receptor antagonist (IL-1ra) is a naturally occurring inhibitor to IL-1 and acts by binding to the IL-1 receptor without activating it. The protein has been shown to decrease tumor growth, angiogenesis, and metastases in murine xenograft models. Our focus in this review is to summarize the known data on the role of IL-1 in tumor progression and metastasis and the use of IL-1 inhibition as a novel therapeutic approach in the treatment of solid organ malignancies.     

Bone Replacement Materials in Hand Surgery

Abstract Background: In recent years, biomaterials are being found and frequently utilized in bone defects. They have also gained significant precedence in hand surgery. Objectives: The respective requirements for such replacement material will be cited and acknowledged in this article. The individual material groups will also be referred to in this review. An introduction to some of the customary bone replacement materials will be cited and concluded with a corresponding recommendation. Conclusion: The implantation of autologous cancellous bone is still regarded today as the “gold standard”. Nevertheless, the usage of bone replacement material can be an enormous advantage in certain indications. The original article can be found online at There was an error in the author’s affiliation and the address for correspondence was incomplete. Please note the correct institution and complete address: Department of Orthopedics and Traumatology, Hand-, Foot- and Reconstructive Surgery, Kreiskrankenhaus Gummersbach GmbH, Germany. Alexander von Friesen, MD Department of Orthopedics and Traumatology, Hand-, Foot- and Reconstructive Surgery Kreiskrankenhaus Gummersbach GmbH Wilhelm-Breckow-Allee 20 51643 Gummersbach Germany Phone (+49/2261) 171-575, Fax -449 e-mail: Friesen@kkh-gummersbach.de     

Evaluation and treatment of chemonucleolysis failures

Fifty patients underwent chemonucleolysis for the treatment of lumbar disk herniations unresponsive to conservative therapy. In patients treated with chymopapain, unrelieved sciatica was the most common cause of clinical treatment failure. Eight patients (16%) experienced no relief or only a transient reduction in their radicular symptoms following chymopapain injection. All eight patients were clinically reevaluated and underwent repeat neuroradiographic studies. Computed axial tomography and lumbar myelography demonstrated persistent nerve root compromise at the level of the injected disk space. Open diskectomy was performed in all eight cases. Postoperatively, seven patients noted complete resolution of their radicular symptoms; one patient had intermittent low back and leg pain following surgery.     

Molecular Interaction of Droperidol with Human Ether-a-go-go-related Gene Channels: Prolongation of Action Potential Duration without Inducing Early Afterdepolarization

Background: The cardiac safety of droperidol given at antiemetic doses is a matter of debate. Although droperidol potently inhibits human ether-a-go-go-related gene (HERG) channels, the molecular mode of this interaction is unknown. The role of amino acid residues typically mediating high-affinity block of HERG channels is unclear. It is furthermore unresolved whether droperidol at antiemetic concentrations induces action potential prolongation and arrhythmogenic early afterdepolarizations in cardiac myocytes.

Methods: Molecular mechanisms of HERG current inhibition by droperidol were established using two-electrode voltage clamp recordings of Xenopus laevis oocytes expressing wild-type and mutant channels. The mutants T623A, S624A, V625A, Y652A, and F656A were generated by site-directed mutagenesis. The effect of droperidol on action potentials was investigated in cardiac myocytes isolated from guinea pig hearts using the patch clamp technique.

Results: Droperidol inhibited currents through HERG wild-type channels with a concentration of half-maximal inhibition of 0.6-0.9 [mu]m. Droperidol shifted the channel activation and the steady state inactivation toward negative potentials while channel deactivation was not affected. Current inhibition increased with membrane potential and with increasing duration of current activation. Inhibition of HERG channels was similarly reduced by all mutations. Droperidol at concentrations between 5 and 100 nm prolonged whereas concentrations greater than 300 nm shortened action potentials. Early afterdepolarizations were not observed.