Aminobisphosphonate inhibition of interleukin-1—induced bone resorption in mouse calvariae

Interleukin-1 (IL-1) is probably an important lymphokine mediator of inflammation and bone resorption. IL-1 derived from mononuclear cells, a melanoma cell line (MM96 cells), and recombinant human IL-1 (rHuIL-1β) increased in vitro bone resorption, as measured by the release of ⁴⁵Ca from cultured mouse calvariae. The 50% maximum active resorption was observed with 0.125 ng/ml or approximately 10⁻¹¹M rHuIL-1β. The resorptive action of IL-1 was not entirely dependent on prostaglandin mediation, since its effect was evident when prostaglandin synthesis was inhibited in the cultures by indomethacin. IL-1—induced resorption has been shown to be inhibited by 10⁻⁵M 3-amino-1-hydroxypropylidene-1-1-bisphosphonate (APD). This inhibition was partially reversed by increasing doses of IL-1. In vitro toxicity studies showed that at concentrations of 10⁻⁴M, APD inhibited the growth of cultured MM96, murine myelomonocytic P388D1, and rat osteosarcoma UMR 106 cells, but not other mast and lymphoid cell lines. These in vitro observations may have relevance to the use of APD in bone and joint diseases in which inflammation and bone resorption are prominent.     

The correlation of axillary ultrasonography with histologic breast cancer downstaging after induction chemotherapy

BACKGROUND: The goal of this study was to examine the role of ultrasonography in detecting axillary lymph node metastases in stage II breast cancer patients after induction chemotherapy (IC). METHODS: Of 172 consecutive patients with T1-3, N0-1, M0 breast cancer registered in a prospective IC trial, a subset of 130 evaluable patients were chosen, with (1) both physical and ultrasonographic examinations of the axilla before and after IC; (2) exactly four cycles of IC; (3) no presurgical radiation therapy; and (4) an axillary lymph node dissection. RESULTS: Before IC, 32 patients (25%) were negative for axillary involvement by both physical and ultrasonographic examinations. After IC, this number increased to 64 (49%). Of these, 31 (48%) were positive by pathology examination. In most cases, however, the residual tumor was minimal. CONCLUSIONS: Stage II breast cancer patients who were or became node negative by both ultrasonographic and physical examinations after IC had a 48% incidence of nodal metastases. Because the residual tumor was minimal, irradiation may be sufficient for adequate local control of the axilla.