Diffusion tensor imaging discriminates between glioblastoma and cerebral metastases in vivo

In a prospective study, patients with a radiologically proven brain tumour underwent diffusion tensor imaging (DTI) prior to definitive diagnosis and treatment. Twenty‐eight patients with a histologically proven glioblastoma or metastasis were included in the study. Following the definition of regions of interest, DTI metrics [mean diffusivity (MD) and fractional anisotropy (FA)] were calculated for the tumour volume and the surrounding region of peritumoral oedema. These metrics were then subjected to logistic regression to investigate their ability to discriminate between glioblastomas and cerebral metastases. A cross‐validation was performed to investigate the ability of the model to predict tumour. The logistic regression analysis correctly distinguished glioblastoma in 15 of 16 cases (93.8%) and metastasis in 11 of 12 cases (91.7%). Cross‐validation resulted in the model correctly predicting 14 of 16 (87.5%) glioblastomas and 10 of 12 (83.3%) metastases studied. MD was significantly higher (p = 0.02) and FA was significantly lower (p = 0.04) within the oedema surrounding metastases than within the oedema around glioblastomas. MD was significantly higher (p = 0.02) within the tumour volume of the glioblastomas. Our results demonstrate that, when DTI metrics from the tumour volume and surrounding peritumoral oedema are studied in combination, glioblastoma can be reliably discriminated from cerebral metastases. Copyright © 2010 John Wiley & Sons, Ltd.     

Antiproliferative effect of exemestane in lung cancer cells

Background  

Recent evidence suggests that estrogen signaling may be involved in the pathogenesis of non-small cell lung cancer (NSCLC). Aromatase is an enzyme complex that catalyses the final step in estrogen synthesis and is present in several tissues, including the lung. In the current study we investigated the activity of the aromatase inhibitor exemestane in human NSCLC cell lines H23 and A549.     

Lack of transmission of neutrophil and platelet antibodies by intravenous immunoglobulin in bone marrow transplant patients

BACKGROUND: Several studies have demonstrated that the administration of intravenous immunoglobulin (IVIG) may be followed by the transient appearance of positive red cell antibody screens, positive direct antiglobulin tests, and, occasionally, frank hemolysis. However, little information is available regarding the possibility that IVIG could transmit neutrophil and/or platelet antibodies. STUDY DESIGN AND METHODS: Serum samples were obtained both immediately before and immediately after the administration of 12 separate lots of commercially available IVIG to bone marrow transplant patients. RESULTS: None of the patients were shown by standard granulocyte immunofluorescence testing to have acquired neutrophil antibodies. Four of the 12 postinfusion sera were positive for platelet antibodies in standard platelet suspension immunofluorescence testing, but in all four instances the corresponding preinfusion serum was positive as well. CONCLUSION: The risk of acquiring neutrophil and/or platelet antibodies after the administration of commercially available IVIG appears to be low.     

Partial purification and characterization of a growth factor for macrophage progenitor cells with high proliferative potential in mouse bone marrow

A population of macrophage progenitor cells, with high proliferative potential, has recently been demonstrated in postfluorouracil-treated and normal mouse bone marrow (BM) in vitro, when the newly discovered growth factor (synergistic activity, SA) is combined with a macrophage colony-stimulating factor (CSF) as a proliferative stimulus. SA, shown to be present in human spleen and placental conditioned media (HSCM and HPCM, respectively) have been studied and found to be unstable to trypsin digestion and to heating at 50 degrees C or above; stable between pH 4 and 9; nonadherent to Con-A-Sepharose; and to have an isoelectric point between pH 5 and 5.8 and a molecular weight of between 14,000 and 21,000 as indicated by gel filtration chromatography. SAs from both HSCM and HPCM have been purified 89- and 122-fold, respectively, by precipitation of extraneous proteins at pH 5 followed by chromatographing twice on Sephacryl S200. Neither of these partially purified SAs contain any CSF for mouse BM. These results indicate that the SAs from HSCM and HPCM may be closely related and that they are structurally different from CSFs derived from various murine sources that have been shown to be stable to proteolytic enzymes and heat.     

Kaposi's sarcoma (KS)-associated herpesvirus-like DNA sequences in peripheral blood mononuclear cells: association with KS and persistence in patients receiving anti-herpesvirus drugs

Herpesvirus-like DNA sequences (KSHV/HHV-8) have recently been described in AIDS-associated Kaposi's sarcoma (KS) lesions. Many questions remain regarding the role of this virus in KS and the therapeutic implications of this finding. In the current study, KSHV/HHV-8 DNA was detected in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus (HIV)-infected patients with KS (34/98) more often than in HIV-infected individuals without KS (12/64, P = .03). The detection of KSHV/HHV-8 DNA did not correlate with the CD4 lymphocyte count. Five patients demonstrated KSHV/HHV-8 DNA in their PBMCs during administration of intravenous foscarnet and/or ganciclovir. The continued detection of KSHV/HHV-8 DNA in the PBMCs of patients receiving these anti-herpesvirus drugs has potential implications regarding the virus-cell relationship of KSHV/HHV-8, as well as for the value of these drugs in treating or preventing KS, but additional studies are needed.     

Loss of myeloid differentiation antigens precedes blastic transformation in chronic myelogenous leukemia

In order to determine whether antigenic patterns alter with disease progression and are thereby suggestive of impending blast crisis in chronic myelogenous leukemia, 50 bone marrow biopsy specimens from 32 patients were examined retrospectively using indirect immunoperoxidase labeling with three monoclonal antibodies that detect myeloid antigens. Monoclonal antibodies PMN13F6, PMN7C3, and PMN8C7 detect human neutrophil antigens that first appear at the myeloblast, promyelocyte, and metamyelocyte stages of differentiation, respectively, and persist throughout later differentiation. Percentages of antigen-positive bone marrow cells during the chronic phase were compared with percentages of antigen-positive cells at blast transformation, and time from bone marrow biopsy until blast crisis was correlated with the percentage of bone marrow cells expressing these antigens. Bone marrow biopsy samples from patients in the chronic phase who continue to remain clinically stable 4 to 106 months after biopsy expressed PMN13F6 antigen on 82% +/- 9% (mean +/- SD) of cells, PMN7C3 antigen on 62% +/- 14% of cells, and PMN8C7 on 68% +/- 14% of cells. Bone marrow biopsy specimens obtained from patients 1 or more years prior to blast transformation expressed PMN13F6 antigen on 81% +/- 12%, PMN7C3 antigen on 71% +/- 16%, and PMN8C7 on 64% +/- 16% of cells. Bone marrow biopsy samples obtained between 2 months and 1 year prior to blast crisis expressed PMN13F6 antigen on 68% +/- 15%, PMN7C3 on 51% +/- 17%, and PMN8C7 antigen on 46% +/- 18% of cells. Bone marrow biopsy specimens taken at the time of blast transformation expressed PMN13F6 antigen on 20% +/- 25%, PMN7C3 antigen on 19% +/- 25%, and PMN8C7 antigen on 13% +/- 25% of cells. The difference between the mean of antigen-positive cells from bone marrow biopsy samples obtained at the time of blast crisis was significant compared with the mean of positive cells from biopsy specimens obtained at all other phases of the disease (P less than .001 for all three antibodies). There was a positive correlation between loss of myeloid antigens and disease progression as determined by simple regression of log time and correlation analysis (PMN13F6, r = .6533, P less than .005; PMN7C8, r = .6304, P less than .005; PMN8C7, r = .5215, P less than .05). There was a negative correlation between percentage of immature cells and time to blastic crisis (r = -.6206, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification of residues in the first and fourth helices of human granulocyte-macrophage colony-stimulating factor involved in biologic activity and in binding to the alpha- and beta-chains of its receptor

Residues within the first and fourth helices of human granulocyte- macrophage colony-stimulating factor (hGM-CSF) were analyzed for their role in biologic activity and interaction with the alpha- and beta- chains of the hGM-CSF receptor. Within the first helix substitution of the surface residues Glu14, Asn17, Gln20, Arg23, Arg24, and Asn27 or the buried residues Ala18, Leu25, and Leu28 did not significantly impair bioactivity or receptor binding. Substitutions at the buried residues Ala22 and Leu26 had intermediate bioactivity. However, substitutions of the surface residue Glu21 or the buried residue Ile19 reduced the relative bioactivity of the analogues to as little as 0.45% and 0.3%, respectively. Substitution of the charged surface residues of the fourth helix showed that substitution at Glu104, Lys107, and Lys111 had no significant effect on bioactivity, but substitution at Glu108 and Asp112 reduced the potency of the analogues to 34% and 7%, respectively. Receptor binding studies showed that, whereas Glu21 is the critical residue for binding to the hGM-CSF-receptor beta-chain, Asp112 is likely to be involved in binding to the GM-CSF-receptor alpha- chain. These results establish the relative contribution of residues in the first and fourth helices for GM-CSF bioactivity and receptor binding, and support a model where the fourth helix of GM-CSF interacts with the alpha-chain, and the first helix with the beta-chain of the GM- CSF receptor.