Increased expression of TGF-beta1 reduces tumor growth of human U-87 Glioblastoma Cells in vivo.

The role that transforming growth factor beta1 (TGF-beta1) plays in influencing growth of glioma cells is somewhat controversial. To further understand the potential growth-regulatory effects of TGF-beta1,we constructed an animal astroglial tumor model by injecting either wild-type or virally transduced human U-87 glioblastoma cells into nude rat brains. Wild type U-87 cells produced very low amounts of TGF-beta1 and were highly tumorigenic. In contrast, U-87 cells transduced to express high levels of TGF-beta1 showed reduced tumor size in vivo, in a dose-dependent manner. This reduction in tumor size was not due to either decreased vascularity or increased apoptosis. To test whether TGF-beta1 overproduction inhibited tumor growth through an autocrine mechanism, the highest TGF-beta1 producing cells were then double transduced with a vector expressing the kinase-truncated type II TGF-beta receptor. Cells expressing high levels of truncated TGF-beta receptor were less sensitive to TGF-beta1 mediated growth inhibition in vitro and produced more aggressive tumors in vivo. The data suggest that the degree of tumorigenicity of the U-87 high-grade glioblastoma cell line may be associated with correspondingly low level of production of TGF-beta1. These results also would tend to support the possibility that TGF-beta1 may be useful in treating some high-grade gliomas.

Recurrence of nodal diffuse large B-cell lymphoma as intravascular large B-cell lymphoma: is an intravascular component at initial diagnosis predictive?

We report a case of a 59-year-old man who first presented with a nodal diffuse large B-cell lymphoma that later relapsed as an intravascular large B-cell lymphoma. In the initial biopsy specimen, a few intranodal small vessels that contained large lymphoma cells were noted. After 8 months of multiagent chemotherapy, clinical remission was attained. Two years after the initial diagnosis of nodal diffuse large B-cell lymphoma, the patient presented with a rapid onset of multiorgan failure, which at autopsy was shown to be due to intravascular large B-cell lymphoma. Molecular genetic studies showed that these 2 lymphomas had immunoglobulin heavy-chain gene rearrangements that were of identical size, suggesting that they were derived from the same clone. To our knowledge, this is the first report of a nodal large B-cell lymphoma that relapsed as an intravascular large B-cell lymphoma. Although this report is of only a single case, the presence of a relatively inconspicuous intravascular component in an otherwise typical nodal large B-cell lymphoma may be predictive and could affect clinical decisions regarding diagnosis, monitoring, and prognosis of such lymphomas.

Apoptosis as a form of cell death in intracerebral hemorrhage.

OBJECTIVE: The goals of this study were to identify and quantify the presence of programmed cell death (apoptosis) in intracerebral hemorrhage (ICH) among human subjects. Recent evidence from laboratory models suggests that cell death in the perihematoma region may involve apoptosis. METHODS: Retrospective clinical and histological analyses were performed for patients with spontaneous ICH who underwent surgical evacuation. Quantification of apoptotic cells was performed in sections obtained from the perihematoma region from 12 patients with ICH and stained with the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling method. Necrosis was identified on the basis of morphological criteria, using hematoxylin and eosin staining. RESULTS: Evidence of apoptosis was present in surgical specimens obtained from 10 of the 12 patients. The mean number of apoptotic cells in the perihematoma region in each patient specimen was 38% (range, 0-90%). For five patients, more than one-half of the total cells observed were apoptotic. Apoptosis was observed in specimens obtained within 1 day, 2 days, and 5 days after the onset of symptoms. No terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling-positive cells were observed in specimens from the two patients with cerebellar hematomas. The mean proportion of necrotic cells in the perihematoma region in each patient specimen was 25% (range, 0-100%). There was a prominent excess of apoptotic cells, in comparison with necrotic cells, for 6 of the 12 patients who underwent hematoma evacuation. For five other patients, similar proportions of apoptotic and necrotic cells were observed. Necrosis was the predominant finding for only one patient, who underwent late surgical evacuation on Day 5. CONCLUSION: These observations suggest that apoptosis represents a prominent form of cell death associated with ICH in the perihematoma region. Further studies are required to define the mediators of apoptosis in ICH.