A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer.

BACKGROUND: Treatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-ß2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment. METHODS: Stage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival. RESULTS: This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p=0.594). There were also no differences in progression-free survival (4.3months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p=0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p=0.002) and that prior radiation was a positive prognostic factor (median survival 28.4months with belagenpumatucel-L versus 16.0months with placebo; HR 0.61, p=0.032). CONCLUSIONS: Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.

Immunoglobulin kappa gene expression after stable integration. I. Role of the intronic MAR and enhancer in plasmacytoma cells.

Rearranged MOPC41 immunoglobulin kappa gene constructs have been stably introduced into cultured S194 mouse plasmacytoma cells to investigate the effects of deleting the intronic enhancer and/or matrix association region (MAR) on gene expression. Intact single-copy kappa genes containing 1.5 kilobase pairs of upstream and 8.5 kilobase pairs of downstream flanking sequences exhibited sensitivity to chromosome position effects and were expressed at a mean level of 27% relative to the endogenous kappa gene expression or only 6% with respect to the MOPC41 kappa mRNA levels in the tumor. Deletion of the intronic MAR led to a 4-fold decrease in expression, while deletion of both the MAR and enhancer led to an 11-fold decline. These effects were dampened by preselecting for integration into a transcriptionally poised chromatin location as demonstrated by linkage to a selectable marker which lacked both a MAR and an enhancer. Significantly, we found that sequences downstream of the poly(A) addition site compensated 150-fold for deletion of the intronic enhancer.

Diffuse pulmonary gallium accumulation with a normal chest radiogram in a homosexual man with Pneumocystis carinii pneumonia. A case report.

A homosexual man with A.I.D.S. (acquired immunologic deficiency syndrome) and pneumocystis infestation was found to have diffuse Ga-67 uptake in the lungs with a coincident negative chest x-ray. While Ga-67 accumulates diffusely in the lungs in a variety of conditions, the present case is the first described in a patient with A.I.D.S. in which Ga-67 was positive before roentgenographic abnormalities were demonstrated. Thus, the use of Ga-67, when A.I.D.S. is suspected, could help establish a diagnosis more promptly.

Prostaglandin in milk, days open, and estrus detection in dairy cows treated with prostaglandin F2 alpha.

Prostaglandin F2 alpha was used to induce estrus in postpartum dairy cows to decrease calving interval and time spent on heat checks. The amount of prostaglandin residue in milk after treatment also was investigated. Twenty-two control cows, checked for heat twice daily, were bred at estrus after 55 days postpartum. Sixty-three cows checked on days 55 to 60 were either bred if in estrus or treated with 30 mg of prostaglandin F2 alpha injected intramuscularly on day 60 and bred at induced estrus or at 75 h posttreatment. Twelve cows were in heat between days 55 and 60 and were bred. Twenty-nine of 51 treated cows were seen in estrus; all of these were bred and 51.7% conceived at this time. Treated cows had fewer days to first service than did controls, but days open were not different, 105.7 versus 101.8. Fertility was similar. Controls required more heat checks than did treated cows (39 to 8.2). Milk from 17 cows at two milkings before and ten milkings after treatment had similar concentrations of prostaglandin (698 +/- 27 pg/ml) except for the first posttreatment milking when prostaglandin concentration almost doubled (1.293 +/- 143 pg/ml).