Aziridinylbenzoquinone in recurrent, progressive glioma of the central nervous system. A Phase II study by the Illinois Cancer Council

Aziridinylbenzoquinone (AZQ) was studied in a Phase II protocol for persons with glioma of the central nervous system (CNS) recurrent or progressive after surgery and radiotherapy. Patients received AZQ, 30 mg/m2 intravenously every 3 weeks if previously untreated or 27.5 mg/m2 if previously exposed to cytotoxic drugs. Partial response was defined as a reduction of at least 50% reduction in the product of the two longest perpendicular diameters of the indicator lesion persisting for a minimum of 28 days. Twenty-eight patients are evaluable for response at this time. Objective response (OR) occurred in four (14.3%): two complete and two partial. Stabilization of disease (SD) was seen in 7 (25.0%). Median survival, in weeks, was greater than 46.0 for responders, 41.7 for SD, and 19.3 for those with progressive disease. The survival experiences are significantly different (P = 0.030 [Breslow]). The OR rate was 21.1% in 19 without prior chemotherapy and 0% in 9 previously treated patients. There were two AZQ-related deaths in patients with prior exposure to nitrosoureas (1 CNS hemorrhage; 1 aspiration pneumonia). One patient had an anaphylactic reaction. Three patients whose tumor initially increased in size subsequently had marked tumor shrinkage. AZQ is an active agent that must be used with added caution in patients who have received nitrosoureas. Initial tumor enlargement may precede response. Although response appears to prolong survival, the correlation between stabilization of disease and survival is not well-defined.     

Multiple lentigines syndrome. Case report and review of the literature.

The multiple lentigines syndrome is reviewed and a new case is presented. The major features of this syndrome are lentigines and other cutaneous abnormalities, cardiac defects, meurologic defects, cephalofacila dysmorphism, shortness of stature, skeletal anomalies, genitourinary abnormalities, and a family history consistent with an autosomal dominant mode of inheritance. The multiple lentigines syndrome manifests markedly variable expressivity; no single finding is pathognomonic and few patients have all major features. We propose specific criteria for diagnosis.     

Radiation-induced cell death and dendritic cells: potential for cancer immunotherapy?

Dendritic cells are key orchestrators of the immune system. There is considerable interest in their use for treating cancer. Whether they initiate an effective cytotoxic response against antigen-bearing cells, or produce tolerance, depends on the context in which those antigens are presented. Ionising radiation, and the cell death it causes, has several properties that may facilitate such an effective response. A range of in-vitro and in-vivo data supports this, although potential problems exist that may require concurrent strategies.     

Genetic and behavioral aspects of pharmacologically induced arousal

Summary Previously reported studies have shown clear differences among strains of inbred mice in response to a variety of novel situations and to certain pharmacologic agents. The purpose of the present study was to test the tenability of the hypothesis that such behavioral differences between genetically distinct groups may be a function of arousal system differences. To achieve this objective while using a pharmacologic method, the investigators assumed: (1) that the state of arousal of the organism is isomorphic to the effects of certain depressant and excitatory drugs; and (2) that a direct relation exists between quantitative differences in overt behavior and the cumulative effects of the drug. Four drugs were selected which could produce measurable changes on an arousal continuum from sleep (pentobarbital), through quiescence (chlorpromazine) and alertness (amphetamine), to convulsions (pentylenetetrazol). Similarly, four strains of mice were selected which show related differences in normal activity: BALB/c, C3H/An, DBA/2, and C57BL/6.Although significant strain differences appeared in base-activity levels as well as in the responses to the standard doses of the drugs and of the placebo, only the responses to pentobarbital and amphetamine were entirely consistent with an arousal hypothesis. The duration of the effect of pentylenetetrazol was also consistent but the latency of that effect was not. At best, the effect of chlorpromazine was that of a mild stimulant, contrary to the justification for its inclusion in this study. Clearly the rigid adherence to any one theoretical orientation in the interpretation of strain-activity phenomena is premature.This research was supported by an AEC contract, No. AT (40-1)-2186, with Vanderbilt University, Nashville, Tenn.