Proangiogenic role of tumor-activated hepatic stellate cells in experimental melanoma metastasis

Myofibroblasts infiltrate malignant liver tumors, although their pathogenic implications are unclear. Immunohistochemical detection of alpha-smooth muscle actin, glial fibrillary acidic protein (GFAP), and CD31 and CD34 expression was used to analyze the contribution of myofibroblasts to angiogenesis in hepatic metastasis produced by intrasplenically-injected B16 melanoma (B16M). Because activated hepatic stellate cells (HSCs) are oxygen-sensing myofibroblasts producing vascular endothelial growth factor (VEGF), the effect of B16M and human A375 melanoma supernatants on VEGF production by immortalized rat HSC line T6 and primary cultured human HSCs also was studied under an hypoxic atmosphere mimicking a tumor microenvironment. Myofibroblast infiltration preceded endothelium recruitment in avascular micrometastasis and generated specific stroma for sinusoidal-type and portal-type angiogeneses. Thereafter, myofibroblasts and endothelial cells colocalized within both angiogenic patterns and their numerical densities correlated with metastasis development. Myofibroblasts often were GFAP-positive, suggesting an HSC origin. Melanoma supernatants stimulated VEGF messenger RNA and protein synthesis by HSCs. These effects were potentiated by hypoxia. VEGF up-regulation was accompanied by increased expression of cyclooxygenase type 2 (COX-2) and PGE2 synthesis. HSC production of VEGF decreased under COX-2 inhibition, whereas it was increased by exogenous PGE2. The high VEGF expression in HSCs induced by melanoma factors and hypoxia resulted in mitogenic, antiapoptotic, and motogenic stimulation of both murine hepatic sinusoidal endothelium and human umbilical vein endothelium. In conclusion, temporal and positional relationships evolve between myofibroblast and endothelium recruitment during metastasis development. Mechanistically, hypoxic induction of VEGF in tumor-activated HSCs may create a proangiogenic microenvironment, facilitating endothelial cell recruitment and survival during hepatic metastasis transition from an avascular to a vascular stage.     

Value of ultrasound-guided core biopsy in the diagnosis of malignant lymphoma

PURPOSE: Ultrasound-guided core needle biopsy for the diagnosis and management of malignant lymphomas is controversial and has not been accepted as an alternative to surgical biopsy. We investigate the clinical usefulness of this procedure in a large series of patients. METHODS: Over a 5-year period (2000-2004), ultrasound-guided core needle biopsies were performed in 102 malignant lymphomas. Five diagnostic categories were considered: large B-cell lymphomas (LBCL), small B-cell lymphomas (SBCL), Hodgkin's disease (HD), T cell lymphomas, and miscellaneous. Surgical excisional biopsy of the node was performed in 47 cases (46.1%) for diagnostic confirmation. RESULTS: The overall diagnostic accuracy of ultrasound-guided core needle biopsy was 88.2% (90/102). SBCL (39), LBCL (36), HD (15), T cell lymphomas (5), and miscellaneous (7) [including T cell-rich B cell (2), natural killer cell (1), Burkitt's lymphoma (1), and non-Hodgkin's lymphoma of the B cell type, NOS (3)] were correctly diagnosed. Three HDs, 1 natural killer cell lymphoma, 1 follicular lymphoma, and 1 LBCL were not correctly diagnosed. The core needle biopsy did not yield tumor tissue in 6 cases. CONCLUSIONS: Ultrasound-guided core needle biopsy is effective in the diagnosis of malignant lymphomas and can be used as the first diagnostic approach in selected clinical situations.     

Surgical approach to the locoregional recurrence of cancer of the rectum

A literature review has been made on the pelvic recurrence of rectal cancer using the MedLine, Ovid, EMBASE, Cochrane and Cinahl data bases. Assessment of the locoregional recurrence must be made using imaging tests in order to rule out the presence of metastasis, as well as for locating its exact location within the pelvis. As the only curative treatment should be complete resection of the recurrence with negative margins, a pre-operative CT, NMR, endorectal ultrasound and PET-CT must be performed to determine its resectability. For a potential cure, radical resections must be made, with the technique varying according to whether the location is central (axial), posterior (presacral) or lateral, as well as treatment directed at the primary tumour. Neoadjuvant treatments, brachiterapy and intra-operative radiotherapy improve the local control results and survival in these patients.     

A fungicidal monoclonal antibody protects against murine invasive candidiasis

Mice infected by Candida albicans and treated with monoclonal antibody C7 survived longer than saline-treated animals. A prozone-like effect was observed. The in vitro candidacidal activity of macrophages was strongly enhanced when C. albicans was opsonized by C7 and complete murine serum was present.