Rationale for carbon ion therapy in high-grade glioma based on a review and a meta-analysis of neutron beam trials

PurposeThe standard treatment of high-grade glioma is still unsatisfactory: the 2-year survival after radiotherapy being only 10–25%. A high linear energy transfer (LET) ionising radiotherapy has been used to overcome tumour radioresistance. An overview of the field is needed to justify future prospective controlled studies on carbon ion therapy.Materials and methodsA meta-analysis of clinical trials on neutron beam therapy and a literature review of clinical investigations on light ion use in high-grade glioma were carried out.ResultsFour randomised controlled trials on neutron beam therapy were retained. The meta-analysis showed a non-significant 6% increase of two-year mortality (Relative risk [RR] = 1.06 [0.97–1.15]) in comparison with photon therapy. Two phase I/II trials on carbon and neon ion therapy reported for glioblastoma 10% and 31% two-year overall survivals and 13.9 and 19.0 months median survivals, respectively.ConclusionThis meta-analysis suggests that neutron beam therapy does not improve the survival of high-grade glioma patients while there is no definitive conclusion yet regarding carbon therapy. The ballistic accuracy and the improved biological efficacy of carbon ions renew the interest in prospective clinical trials on particle beam radiotherapy of glioma and let us expect favourable effects of dose escalation on patients’ survival.     

Antigenicity of peptide 19-28 of toxin II from the scorpion Androctonus australis as measured by different solid-phase tests and characterization of specific antibodies purified by immunoaffinity on the peptide or the toxin

The antigenicity of peptide 19-28, a model of one of the major antigenic regions of toxin II of the scorpion Androctonus australis Hector was tested in different solid phase radioimmunoassay systems. The type of the solid phase and the mode of binding the synthetic peptide to the phase had a considerable effect on the resulting antigenicity. Two subpopulations of anti-toxin II antibodies were purified by affinity chromatography, one on Sepharose-peptide 19-28, the other on sepharose-toxin. The native or chemically modified toxin bound in the same way to these subpopulations. Denatured toxin was only poorly recognized by these antibodies. This suggests that the antibodies purified on peptide 19-28 recognize the same conformation dependent antigenic surface as do total anti-toxin antibodies.     

Accuracy of dual-energy radiographic absorptiometry of the lumbar spine: cadaver study

Dual-energy radiographic absorptiometry (DRA) was used to measure the bone mineral content and area density of lumbar vertebrae (L2-L3) in 11 cadavers. These data were subsequently compared with measured ash content and density. Excellent correlation was obtained between bone mineral content measured with DRA and ash weight (r = .963, P less than .0001). The accuracy error in determining mineral content in lumbar vertebrae with DRA was about 9%. In addition, strong correlation was observed between bone mineral density measured with DRA and ash density (r = .881, P less than .0001).     

ADENOMYOEPITHELIOMA OF THE BREAST

Adenomyoepithelioma is a rare disorder characterised by simultaneous proliferation of ductal epithelium and myoepithelial cells. It is more common in salivary glands or skin, and only rarely found in breast tissue. Adenomyoepithelioma of the breast was first described in 1970 by Hamperl.¹ Since then, approximately 55 cases have been described in the literature; the largest review, by Tavassoli in 1991, reported 27 of these cases.² Because of the small number of cases reported, the natural history of adenomyoepithelioma of the breast remains uncertain. We report a further case which was treated by local excision, and follow-up for two years has revealed no evidence of local recurrence or metastatic spread.     

Cytotoxic T-cell response to ectromelia virus-infected cells. Different H-2 requirements for triggering precursor T-cell induction or lysis by effector T cells defined by the BALB/c-H-2(db) mutation

The T(c)-cell response to ectromelia virus infection was studied in BALB/c-H-2(db) mice which carry a loss mutation in the H-2D region that results in the absence from cell surfaces of a molecule (D’) bearing certain public H-2 specificities. When infected, these mice showed a poor response of T(c) cells that recognize H-2D(d) plus virus-specific determinants on infected macrophage targets, but gave a normal response to H-2K d plus virus-specific antigens. However, their own infected macrophages do display wild-type antigenic patterns involving virus and H-2D(d) since they were killed as efficiently as wild-type (BALB/c,H- 2(d))-infected cells by T(c) cells specific only for H-2D(d) plus viral antigens. When tested in vitro, infected BALB/c-H-2(db) cells stimulated a poor T(c)-cell response to H-2D plus virus-specific antigens, but stimulated a normal response (in comparison with infected BALB/c macrophages) to H-2K(d) plus viral antigens. Uninfected BALB/c-H-2(db) cells stimulated a normal T(c)-cell response to minor H antigens or trinitrophenyl in association with H-2D(d), thus suggesting that the defective response to infection may reside in a failure of the relevant H-2D(d) antigens of mutant cells to physically associate with viral antigens. Close association of viral and H-2D-coded molecules was also suggested by ability of specific anti-H-2K or -H-2D to partially block T(c)-cell-mediated lysis of infected targets. These results were interpreted to mean that H-2Dd-dependent, virus- immune T(c) cells recognized an antigenic pattern consisting of virus- specific and H-2D(d) determinants with the latter borne on an H-2D molecule carrying serologically-defined H-2D(d) private specificities. A second H-2D(d)-coded molecule (D’) was not required for recognition and lysis by activated T(c) cells, but was apparently necessary for efficient stimulation of precursor T(c) cells, perhaps by promoting appropriate physical association of viral and H-2D(d) molecules.     

Kell blood group activity of gram-negative bacteria

To understand better the relationships between blood-group antigens and bacterial constituents, examples of 23 gram-negative bacteria (representing the 10 genera Citrobacter, Edwardsiella, Enterobacter, Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Serratia, and Shigella) were tested for the presence of Kl-like antigens by hemagglutination-inhibition (HAI) assays against both IgG and IgM anti-Kl. Saline-suspended whole organisms, cell-free culture media, and disrupted organisms were used to test for such antigens in, on, and secreted by the microorganisms examined. Disrupted organisms of an isolate of Shigella sonnei nonspecifically inhibited IgG anti-Kl as well as IgG antibodies of the specificities Kpb, Fya, S, and c. However, only Escherichia coli 0125:B15, subtype 12808, had specific K1-like activity (no activity with other IgG [(k, Kpb, Jka, Fya, S, c] and IgM [A, B, M, P1] antibodies). Disrupted organisms inhibited IgM but not IgG anti-K1 in the HAI assay. A second subtype, E. coli 0125:B15, subtype 12809, exhibited no K1-like activity. These findings support the report of K1 activity in cell-free broth cultures of E. coli 0125:B15 (subtype unspecified). Thus, although not all E. coli 0125:B15 possesses K1-like activity, the finding of such activity in at least one E. coli subtype confirms the idea that bacterial components may play a role in the production of naturally occurring antibodies directed against non-ABO red cell antigens.