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In a mouse model the retention of125I-5-iodo-2' -deoxyuridine-labeled tumor cells in the lung after iv injection was compared with the formation of tumor colonies in the lung 15 days after injection. The modification in lung retention after treatment with cyclophosphamide (CP), isophosphamide, Corynebacterium parvum, and heparin paralleled the changes in lung-colony numbers by these treatments. Since the modifications could be identified as early as 1 hour after iv administration of tumor cells, further evidence was obtained for the conclusion reached earlier that the modification of lung metastases by CP and Corynebacterium parvum is not due to immunologic mechanisms. Comparison with the lung retention of heat-killed tumor cells and living embryonic cells showed that CP induced an increased retention of all three cell types. In contrast, Corynebacterium parvum decreased the retention of living tumor cells, but failed to modify the retention of dead tumor cells, but did not affect the retention of living embryonic cells. Since no similar cell types were affected by the various treatments it seems likely that different mechanisms are involved. Apparently CP decreases the nonspecific resistance against the lodging and growth of any type of cell in the lung.

Brains of guinea-pigs were studied using the rapid Golgi technique after formol fixation. The delay between death and fixation varied from 5 min to 24 h. A considerable drop in density of spines on the apical, basal and oblique dendrites of pyramidal V cells was found from 1.5 h onwards. The total length of the basal dendrite arborization showed a reduction after 4 h. It was concluded that, particularly for quantitative methods, a fixation delay of more than 4 h makes results progressively less reliable.

Comparison of response of experimental tumors to adjuvant chemotherapy for minimal disease with the response of solid large tumors to similar drug regimens has indicated that for many tumors the small microscopic foci are more responsive. There are, however, a number of model tumors that respond far less to chemotherapy when applied to minimal disease than when applied to large tumors. The response of these tumors to adjuvant treatment shows similarities with the clinically observed response. The data do not support the hypothesis that the success of a drug combination given as adjuvant chemotherapy may be predicted from the success of the same treatment when applied for manifest disease.

In this study the cellular morphology in the human fascia dentata of 5 very old demented cases (4 Alzheimer's disease and 1 multi-infarct dementia patients) was compared with 5 (very) old controls cases. The postmortem delay in fixation was for all cases within 3.5 h. In the demented group, a significant reduction in thickness of the molecular layer, density of dendritic spines in the middle third of the molecular layer and total dendritic length (+/- 30%) was found. The number of dendritic segments, indicative of the branching frequency showed no difference. In both the control and the demented group, three-quarters of all dendritic bifurcations of granule cells occurred in the inner third of the molecular layer in which the commissural and associational fibers terminate. The size of the dendrites in the demented group could be the result of at least 3 independent processes: a regressive change due to partial denervation of the outer two-thirds of the molecular layer as axons from the perforant pathway are lost; a dendritic regrowth in response to sprouting of the commissural-associational fiber systems and septal afferents, which is presumed to occur in response to degeneration of perforant path axons; a dendritic regrowth in response to the loss of the dendrites of neighboring cells which have died. Analysis of our material suggests that dendritic degeneration is the predominant factor in the demented group.

We have focused on three aspects of adjuvant chemotherapy applied to mice with one of the metastasizing tumors: Lewis lung carcinoma (LL) or mammary carcinoma 2661 (M2661). The first aspect concerned the timing of adjuvant chemotherapy. To investigate this, tumor-bearing mice were treated postoperatively with cyclophosphamide using a standard regimen. In M2661, adjuvant therapy was marginally effective in contrast to the clearly significant results obtained in LL. Any delay in the initiation of adjuvant therapy decreased the efficacy of the treatment. The effect of administering chemotherapy before surgery was also studied; normally, marginally effective adjuvant therapy was found to become effective when started preoperatively in M2661. In LL, effective adjuvant therapy was found to become less effective when started preoperatively. The second aspect considered was the comparability between the increase in relapse-free survival time and the increase in cure rate as alternate goals of adjuvant therapy. To study this, mice with small, medium, or large residual tumor loads were subjected to surgery and subsequently treated with cyclophosphamide. While the effect of adjuvant therapy on the cure rate increased proportionally with decreasing tumor load, the increase in lifespan in nonsurvivors was not related to tumor load. The final aspect of study was the selection procedure for drugs to be applied in adjuvant treatment in our models. Taking the volume response of large tumors as being predictive for the successful use of the same agent in adjuvant therapy, we obtained both false-negative and false-positive results in our tumor lines.

The c-myc gene contains 2 well conserved polyadenylation (pA) sites. In all human and rat cell lines from various differentiation stages and tissue types the amount of mRNA terminating at the second pA site is 6-fold higher than the amount ending at the upstream site. This is not due to a difference in stability of the two mRNA types and therefore must be due to preferential usage of the downstream site. The usage of the pA sites is not altered during growth factor induction of quiescent cells. We have not been able to detect differences in behavior between mRNAs ending at either pA site. Both types of mRNA are induced upon treatment of cells with cycloheximide. Furthermore, we have shown that the poly(A) tail of c-myc mRNA is lost during degradation of the messenger, as was described previously for c-myc mRNA in an in vitro system. The time required for the loss of the poly(A) tail is similar to the half-life of c-myc mRNA.

As part of a larger study on the quality of life of cancer patients under treatment, the positive and negative experiences in social interaction have been examined as compared to those of a control group (nonpatients, n = 201). Two patient groups were included: 109 patients who had recently undergone surgery and 108 patients receiving chemotherapy. The respondents returned a mailed questionnaire. Contrary to the assumptions based on a review from the literature, cancer patients appear to have more positive and fewer negative social experiences than a random sample from the 'normal' population. Even under more severe medical circumstances (a poor prognosis or heavy chemotherapy, a large number of chemotherapy cycles, poor progress after surgery) the poorer the patients, medically speaking, the more help and support they perceive. The results of this study do not support the idea of stigmatization. The personality characteristics, neuroticism and self-esteem are especially important for the having of positive and negative experiences in social interaction. Positive social experiences show a relationship with self-esteem and negative social experiences show a relationship with neuroticism.