Pain is one of the most severe and debilitating symptoms associated with several forms of cancer. Various types of carcinomas and sarcomas metastasize to skeletal bones and cause spontaneous bone pain and hyperalgesia, which is accompanied by bone degradation and remodeling of peripheral nerves. Despite recent advances, the molecular mechanisms underlying the development and maintenance of cancer-evoked pain are not well understood. Several types of non-hematopoietic tumors secrete hematopoietic colony-stimulating factors that act on myeloid cells and tumor cells. Here we report that receptors and signaling mediators of granulocyte- and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are also functionally expressed on sensory nerves. GM-CSF sensitized nerves to mechanical stimuli in vitro and in vivo, potentiated CGRP release and caused sprouting of sensory nerve endings in the skin. Interruption of G-CSF and GM-CSF signaling in vivo led to reduced tumor growth and nerve remodeling, and abrogated bone cancer pain. The key significance of GM-CSF signaling in sensory neurons was revealed by an attenuation of tumor-evoked pain following a sensory nerve-specific knockdown of GM-CSF receptors. These results show that G-CSF and GM-CSF are important in tumor-nerve interactions and suggest that their receptors on primary afferent nerve fibers constitute potential therapeutic targets in cancer pain.

Statement of the Problem:Many regions in the world do not have electricity, water, or access to dental facilities that allows the treatment of caries with dental handpieces and rotary burs. For restorative techniques used in these regions, an antibacterial self-adherent glass ionomer material would contribute considerably.Purpose: This study aimed to test if chlorhexidine diacetate (Fluka BioChemika, Buchs, Switzerland)-or chlorhexidine digluconate (Sigma-Aldrich, Steinheim, Germany)-added ChemFil Superior glass ionomer cement (Dentsply DeTrey, Konstanz, Germany) had any long-term antibacterial effect against certain oral bacteria and to test the new formulation's physical properties. Materials and Methods:ChemFil Superior was used as a control. Chlorhexidine diacetate (powder) was added to the powder and chlorhexidine digluconate (liquid) was mixed with the powder in order to obtain 0.5, 1.25, and 2.5% concentrations of the respective groups. Setting time, compressive strength, and acid erosion were tested according to ISO 9917-1. Working time, hardness, diametral tensile strength, and biaxial flexural strength were also determined. Longterm antimicrobial activity against S. mutans, L. acidophilus, and C. albicans were tested with the agar diffusion method. Analysis of variance (ANOVA) was used for comparison (p < 0.05).Results: Regarding the immediate antibacterial effect for S. mutans, all the tested groups showed inhibitions of the strain compared with the control group (p < 0.05), with larger zones for the higher concentration groups and all the diacetates. For L. acidophilus, all the groups were effective compared with the control, but the greatest antibacterial effect was observed with the 2.5% diacetate group. The 2.5% group of chlorhexidine diacetate showed antibacterial activity up to 90 days against S. mutans and up to 60 days against L. acidophilus. The working and setting time, acid erosion test, diametral tensile strength, and biaxial flexural strength of the tested © 2 0 0 8 , C O P

Background: Extranodal marginal zone B cell lymphoma of the mucosa-associated lymphoid tissue (MALT) is a relatively common type of lymphoma. Owing to its B cell lineage, it appears to be a potential target for treatment with the CD20 antibody rituximab. We present an analysis of our experience with rituximab for treatment of patients with advanced MALT lymphoma. Patients and Methods: A retrospective analysis of patients with histologically verified MALT lymphoma undergoing treatment with rituximab was done. After reassessment of histological samples for the presence of MALT lymphoma, patients were evaluated as regards date of diagnosis, prior therapy for MALT lymphoma, sites of involvement upon treatment with rituximab, clinical response in terms of complete remission (CR), partial response (PR), stable disease (SD) and progressive disease as well as symptomatic response, duration of response and survival. Results: A total of 9 patients with advanced MALT lymphoma undergoing therapy with single-agent rituximab were identified. All patients received treatment at a dose of 375 mg/m² once weekly ×4. One patient each had relapsed after chemotherapy and radiation, respectively, while none of the other 7 patients had received prior cytotoxic treatment or radiation. Three patients achieved a CR, 2 patients had PR for 6 and 14 months, while the remaining patients had SD between 8 and 18+ months. One patient died of progressive disease in spite of the initiation of chemotherapy and 1 patient succumbed to a cardiovascular event while having been in ongoing PR for 11 months. The other 7 patients are currently alive with disease 10–27 months after initiation of therapy. Follow-up biopsies for histological assessment were available in 5 patients with gastric lymphoma. In 1 patient with SD, however, persistence of CD20-positive cells within lymphoepithelial lesions was noted in spite of almost complete depletion of B lymphocytes from the normal gastric mucosa, suggesting either recirculation of MALT lymphoma cells to these lesions or defining lymphoepithelial lesions as a sanctuary site from rituximab penetration. Conclusion: Rituximab had only moderate activity in terms of inducing objective responses in our unselected and heterogeneous cohort of patients with disseminated MALT lymphoma. Long-term disease stabilization, however, along with a symptomatic benefit was seen in all patients. Our data nevertheless indicate that rituximab might not optimally penetrate into the gastric mucosa in all patients.

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