Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence.Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362.

Steroids are commonly administered for the control of edema, mass effect, and side effects from therapy to patients with malignant glioma who are receiving radiotherapy and chemotherapy. Here, we report that therapeutic concentrations of dexamethasone (DEX) attenuate cytotoxicity and growth inhibition of human malignant glioma cells induced by exposure to several chemotherapeutics, including ACNU, VM-26, vincristine, cytarabine, methotrexate, and adriamycin. DEX-mediated cytoprotection is not linked to DEX effects on glioma cell proliferation. However, the cytoprotective effects of DEX appeared to be more prominent in cell lines with wild-type p53 status (n = 2) than in p53 mutant cell lines (n = 3). Further, DEX-mediated rescue from chemotherapy does not directly involve Bcl-2 family proteins since DEX failed to change the expression of Bcl-2 or Bax proteins and since bcl-2 gene transfer-mediated cytoprotection was not redundant with the effects of DEX. DEX thus appears to control a common, bcl-2-independent death pathway in glioma cells that is not limited to specific drug actions. Chemotherapy is usually given as an elective, adjuvant treatment to glioma patients in stable condition who can tolerate steroid withdrawal. To maximize therapeutic efficacy, steroids should be withdrawn from glioma patients prior to chemotherapy.

β‐lapachone and camptothecin are structurally unrelated agents thought to inhibit topoisomerase‐I activity through distinct mechanisms. We find that β‐lapachone is much more potent than camptothecin in inducing acute cytotoxic effects on human malignant glioma cells. Acute cytotoxicity induced by both drugs is apoptotic by electron microscopy, but not blocked by inhibitors of RNA or protein synthesis and not associated with changes in the expression of bcl‐2, bax, p53, p21 or GADD45 proteins. In contrast, prolonged exposure of glioma cells to both drugs for 72 hr results in growth inhibition and apoptosis, with EC50 values around 1 μM. None of 7 glioma cell lines tested were resistant to either drug. LN‐229 cells which have partial p53‐wild‐type activity show enhanced expression of p53, p21 and bax protein, whereas bcl‐2 levels decrease, after exposure to camptothecin. In contrast, β‐lapachone increases bax protein expression in the absence of p53 activation. T98G cells are mutant for p53. In these cells, p53 levels do not change and p21 is not induced. bax accumulation in T98G cells is induced by both drugs, with bcl‐2 levels unaltered. Surprisingly, ectopic expression of murine bcl‐2 fails to abrogate the toxicity of either drug. Camptothecin, but not β‐lapachone, sensitizes human malignant glioma cells to apoptosis induced by the cytotoxic cytokines, tumor necrosis factor‐α and CD95 ligand. Thus, both drugs have potent anti‐glioma activity that may be mediated by enhanced bax expression but is not inhibited by ectopic bcl‐2 expression. Camptothecin‐like agents are particularly promising for immunochemotherapy of malignant glioma using cytotoxic drugs and CD95 ligand. Int. J. Cancer 73:707–714, 1997. © 1997 Wiley‐Liss, Inc.

Background: Early onset lung cancer shows some familial aggregation, pointing to a genetic predisposition. This study was set up to investigate the role of candidate genes in the susceptibility to lung cancer patients younger than 51 years at diagnosis.

Recombinant plasmids having PstI fragments of P22 DNA inserted in the vector pBR322 can be transduced efficiently by Salmonella phage P22, irrespective of the cloned phage sequences. When the rec function of the donor cells and the corresponding recombination system erf of the infecting phage are simultaneously inactivated, only plasmids containing the P22 pac site can be transduced. By this selective, generalized transduction an EcoRV DNA fragment of the P22 related phage L has been identified that carries a base sequence recognized by phage P22 as a packaging signal. Experiments in which only one of the two recombination systems was inactivated, showed that the bacterial rec system obviously promotes cointegrate formation between plasmid and phage DNA much more efficiently than the phage-coded erf system, allowing the specialized plasmid transduction observed by Orbach and Jackson (1982).