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Summary ¶Background. Cell apoptosis in solid tumours has been related to immunological attack by NK-cells. The purpose of the present study is to verify in the tissue of brain metastases a possible relationship among the degree of NK-cell infiltration and the number of apoptotic tumour cells. Methods. Twenty brain metastases whose tumour cells expressed CD95 (Fas/APO1) have been studied. NK-cells were identified by using the monoclonal antibody to CD57, and apoptotic tumour cells by means of the immunostain with the anti-ssDNA monoclonal antibody F7-26. The Spearman rank correlation test was used to study the relationship between the degree of CD57-NK-cell infiltration and the apoptosis labelling-index. Findings. Positivity to F7-26 was present in all tumour samples, but the number of immunostained cells showed a wide variability, with a mean apoptosis labelling-index of 11.48%. All the studied tumours showed CD57 immunostained cells, with a number that ranged between 4 and 20 per microscopical field at 200× (mean±standard deviation: 8.4±3.7). Statistical studies showed that there was no correlation between the number of CD57 immunostained NK-cells and the apoptosis labelling-index (p>0.05). Interpretation. These findings suggest that in brain metastases, apoptosis related to immune r esponse is mainly mediated by activated tumour-infiltrating mononuclear cells other than CD57+ NK-cells. [ABSTRACT FROM AUTHOR]

Summary. Background: Cell proliferation and cell death are opposing processes in tumour growth, with tumour progression reflecting the balance between proliferating and apoptotic cells. The purpose of the present study is to verify the hypothesis that an imbalance between apoptosis and proliferation can predict survival in patients with primary glioblastoma. Methods: After the immunohistochemical study of Apostain and MIB-1 expression, the index of apoptosis (AI), the index of proliferation (PI), and the ratio AI/PI was recorded for each tumour specimen, in a series of 32 primary glioblastomas. Studies of correlation between AI and PI, between AI and survival, between PI and survival, and between the ratio AI/PI and survival, were performed using the Spearman rank correlation test. Furthermore, a comparative study of survival was performed for subgroups of patients with ratio AI/PI greater or lesser than 1, using the log rank test. Findings: In the present series, values of AI and PI showed a wide distribution, with a mean±SD of 8.16±7.2, and of 12.69±21.1, respectively. The values for the ratio AI/PI ranged between 0.01 and 6.03 (mean±SD: 1.44±1.60). Statistical study failed to obtain correlation between AI and PI. Survival of patients not correlated with AI neither with PI. The ratio between AI and PI did not correlate with survival either. Nevertheless, when survival for the subgroups of patients showing a ratio AI/PI greater or lesser than 1 was compared, a significant difference was found (p: 0.02). Survival ranged between 50 and 81 weeks (mean of 58.5±11.05 weeks) for the 12 cases showing a ratio AI/PI greater than 1, and it ranged between 8 and 85 weeks (mean: 38.20±25.37 weeks) for the 20 cases showing a ratio AI/PI lesser than 1. Interpretation: Our present results suggest that a clear imbalance between cell proliferation and apoptosis can predict outcome in patients operated on for a primary glioblastoma. [ABSTRACT FROM AUTHOR]

Intratumoural administration of gangliosides (GSD) into a murine primitive neuro-ectodermal tumour, growing in the epicranial subcutaneous tissue of syngenic rats, results in a decrease in the tumour growth rate and causes a more differentiated phenotype of tumour cell, with immunohistochemical expression of neuronal markers. These findings suggest that the potential usefulness of intralesional administration of GSD for the control of tumours of primitive neuro-epithelial character could be considered. [ABSTRACT FROM AUTHOR]

A series of 122 experimental brain tumours, induced in the Wistar rat by means of prenatal exposition to ethyl-nitrosourea, were studied with histological, immunohistochemical and ultrastructural techniques. Although with conventional histological techniques, most of the induced tumours showed morphological features suggesting their classification as malignant schwannomas or oligodendroglioma-like neoplasms, their study by means of immunohistochemistry and electron microscopy suggested that they are, in fact, primitive neuroectodermal tumours, with a tendency toward neuronal differentiation. This finding obliges us to re-appraise the ethyl-nitrosourea model of neurocarcinogenesis and to consider its possible usefulness for the experimental study of therapeutic approaches with potential applications in human neuro-ectodermal neoplasms. [ABSTRACT FROM AUTHOR]

Delayed transplantation of foetal cerebral tissue into injured spinal cord of adult rats was performed for the purpose of evaluating the usefulness of the procedure for reconstructing the spinal cord and providing motor recovery. Transplanted tissue showed a survival rate greater than 80% and integration with the host tissue. Nerve fibers of the host surrounded the transplanted tissue, penetrating it. Foetal cerebral neurons matured into recipient spinal cord, but they were not organized in layers. The experience obtained suggests that delayed transplantation of foetal cerebral tissue into contused spinal cord is useful in morphological spinal cord reconstruction. Nevertheless, at least during the first two months after transplantation, clinical assessment of motor recovery showed no differences between transplanted and nontransplanted rats. [ABSTRACT FROM AUTHOR]

The presence of NK-cells in a series of 40 metastatic brain tumours has been studied by means of the monoclonal antibody IOT-10. There appeared IOT-10 NK-cells in all tumours studied, but in most cases these cells represented less than 10% of the tumour infiltrating lymphocytes (TIL). In the present series, the obtained data suggest that the number of NK-cells in brain metastases can be influenced by other factors than the mere quantity of TIL. [ABSTRACT FROM AUTHOR]

Preliminary experience with a clinical trial of immunotherapy for glioblastoma, by means of intratumoural injection of autologous lymphocytes (AL) mixed with low doses of human lymphoblastoid interferon (HLI) is presented. In two of twelve patients, a transient reduction of tumoural volume was obtained. Morphological studies showed that injected lymphocytes remain within the tumour, and suggest tumoural lysis due to activity of natural killer (NK) cells. Clinically no significant prolongation of survival time could be achieved and, as in other series, patients with additional radiation therapy survived longer. But the morphological findings suggest that immunotherapy carrying NK-cells to contact with tumoural cells might be useful in some patients with glioblastoma. Actually no explanation can be given why only two of our cases responded positively. Regarding the otherwise poor prognosis it seems justified to continue these studies. [ABSTRACT FROM AUTHOR]

In Part I of this report, the CSF circulatory dynamics of autologous leucocytes labelled with indium-111 and injected in the subarachnoid space, in patients operated on for glioblastoma, were studied. In the Part II, a series of 11 patients with recurrent glioblastoma was studied for evaluating the efficacy of intrathecal injection of autologous leucocytes. Six patients previously had radiotherapy. The results in Part I show that after intrathecal injection of autologous leucocytes, these cells follow throughout the subarachnoid space and pass to the systemic blood circulation, showing no evidence of colonization of the tumour or deposit in the tumoural region. The mean survival of the patients studied in Part II was 8 months. Those six patients who received radiotherapy had a mean survival of 11.4 months, and those five who received only intrathecal injection of autologous leucocytes after surgery, had a mean survival of 4 months. This results seem to demonstrate that immunotherapy, as used in this study, is ineffective in patients with glioblastoma. [ABSTRACT FROM AUTHOR]