DNA in human glioblastomas. A flow-fluorescence cytometrical examination of 96 tumors

Spaar, F. W.; Spaar, U.

doi:10.1007/bf00383653

Cited by 9 publications

(3 citation statements)

References 65 publications

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“…The finding with flow cytometry of an aneuploid peak in all four tested high-grade gliomas and diploid peak in one high-grade and one low-grade glioma agrees with the distribution found by others (Onda et al, 1988;Spaar & Spaar, 1990).…”

Section: Specificity Of the Measured Inhibitionsupporting

confidence: 91%

Growth of cultured human glioma tumour cells can be regulated with histamine and histamine antagonists

Ven¹,

Prinsen²,

Jansen³

et al. 1993

Br J Cancer

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Summary The 50% survival time for low grade astrocytomas is 50 months and for high grade astrocytomas it is 13 months, underlining the need for new therapies. Several reports show that in vivo histamine antagonists cause retardation of tumour growth in some animal models and prolonged survival in cancer patients. Therefore we have tested the growth modulating effects of histamine and histamine antagonists on human glioma cultures.Twelve freshly excised human gliomas were cultured and tested for their in vitro sensitivity to histamine and histamine antagonists. Four continuous glioma cell lines were used to confirm the glioma-specificity of the effects observed in the primary cell lines. In low serum concentration (0 or 1%) the growth of 5/9 primary glioma-derived cultures could be stimulated with 0.2 mm histamine, and in 4/5 cases with 0.2 tLM histamine. One mm of the histamine H2-receptor antagonist cimetidine could inhibit the growth of 4/5 primary glioma cultures when tested in 1% human AB serum, and of 6/13 cases when tested in 1% FCS. Lower concentrations (down to I fLM) were less effective. The histamine HI-receptor antagonist pyrilamine gave variable results.The specificity of the effects is indicated by the absence of a generalised toxic effect, by the observation that the antagonist-induced inhibition could be reversed with histamine, and by the correlation of the obtained cimetidine-induced growth inhibition with the maximal growth rate of the primary cell lines in 10% FCS.The observed cimetidine-induced inhibition of the in vitro proliferation of gliomas suggests that cimetidine is a relevant candidate for the in vivo growth inhibition of these tumours.

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Section: Specificity Of the Measured Inhibitionsupporting

confidence: 91%

Growth of cultured human glioma tumour cells can be regulated with histamine and histamine antagonists

Ven¹,

Prinsen²,

Jansen³

et al. 1993

Br J Cancer

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“…Nuclear DNA content is a useful prognostic factor in a variety of neoplasms, with DNA aneuploidy being generally correlated with poor prognosis (Merkel and McGuire, 1990). The results of neuroepithelial tumor patients are still contradictory in terms of both percentage of aneuploidy (which range from 20% to about 70%) and clinical correlations (Spaar and Spaar, 1990). This disagreement can be ascribed to the different meth-odologic approaches used for the evaluation of DNA histograms and for preparation of cell suspensions and to the limited or selected series of patients studied.…”

Section: Discussionmentioning

confidence: 99%

“…In almost any kind of human malignancy a varying proportion of cases with DNA content abnormalities has been detected by flow cytometric analysis (Coon et al, 1987) and DNA aneuploidy has been correlated with a poorer prognosis in several types of tumor (Merkel and McGuire, 1990). Human brain tumors have been studied repeatedly by FCM (Hoshino et al, 1978;Frederiksen et al, 1978;Mork and Laerum, 1980;Borchers and Beck, 1980) and most studies indicate that FCM aneuploidy prevails in poorly differentiated tumors (Danova et al, 1986a;Ahyal, 1988;Onda et al, 1988;Spaar and Spaar, 1990). The correlation between FCM DNA content and clinical behavior has been addressed only in a few studies, generally containing a limited number of cases analyzed by univariate analysis, which give contradictory results (Danova et al, 1987a;Zaprianov and Christov, 1988;Jimenez et al, 1989;Coons et al, 1990).…”

mentioning

confidence: 99%

Prognostic significance of nuclear DNA content in human neuroepithelial tumors

Danova¹,

Giaretti²,

Merlo³

et al. 1991

Intl Journal of Cancer

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The relationship between survival and flow cytometric DNA-ploidy and other prognostic factors such as histological subtype, anatomical tumor site, patient sex and age was investigated in 153 patients with intracranial neuroepithelial tumors who underwent surgical treatment. We found a trend toward poorer survival from anaplastic astrocytomas and glioblastomas with respect to low-grade (I and II) astrocytomas (which did not differ significantly); accordingly, patients were grouped into these 3 histologic subgroups. Thirty-seven of the 153 tumors (24.2%) were aneuploid with a median DNA-index (DI) of 1.3 (range: 1.2-2.0). DNA-ploidy correlated with histology, since anaplastic astrocytomas and glioblastomas were significantly (p = 0.041) more frequently aneuploid (around 30%) than low-grade astrocytomas (around 10%). Patients with DNA-aneuploid tumors (i.e., with DI not equal to 1.00) survived for a shorter time (31.4 weeks) than patients with DNA diploid tumors (75.1 weeks) (p less than 0.001). This difference was confirmed by Cox's multivariate analysis. Aneuploid tumors were associated with a poorer survival (p = .0002) when compared with diploid tumors, resulting in a relative risk point estimate (RR) of 2.41, 95% confidence interval (Cl) = 1.55-3.74. Histological subtype was also significantly associated with survival (p less than 0.0001), with RRs of 2.09, 95% Cl = 1.13-3.86 and 3.59, 95% Cl = 1.96-6.59 for anaplastic astrocytomas and glioblastomas, respectively, compared to low-grade astrocytomas. We therefore suggest that the flow cytometric measurement of DNA-ploidy has relevant significance in predicting survival in patients treated for intracranial neuroepithelial tumors.

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Histopathologic grading and DNA ploidy in relation to survival among 206 adult astrocytic tumor patients

Salmon¹,

Kiss²,

Dewitte

et al. 1992

Cancer

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Background. The authors studied the benefit of performing histopathologic grading and DNA ploidy char‐acterization with respect to patient survival in a series of 206 astrocytomas (AST) for which they obtained 134 complete clinical follow‐ups. Methods. The material analyzed came from archi‐val material, i.e., formalin‐fixed paraffin‐embedded tis‐sues. DNA ploidy was assessed by means of a cell image processor computing the integrated optical density [IOD] on Feulgen‐stained nuclei. Results. Results showed that histopathologic diag‐nosis in three grades, i.e., AST, anaplastic astrocytoma (ANA), and glioblastoma multiforme (GBM), had a signifi‐cant prognostic value. Patients with AST showed a mean survival time (between histopathologic diagnosis and death) of more than 36 ± 6 months (AST versus ANA or GBM) (P < 0.001). Patients with ANA and GBM showed a mean survival time of 15 ± 2 and 10 ± 1 months, respec‐ tively, (ANA versus GBM) (P < 0.05). Patient age strongly correlated with survival. Patients younger than 40 years of age had a mean survival time of 20 ± 4 months. Pa‐ tients between 41 and 60 years of age had a mean survival time of 12 ± 2 months, and patients older than 60 years of age had a mean survival time of 11 ± 1 months. Conclusions. Considering DNA ploidy characterization, the authors noticed that aneuploid ANA (DNA index [DI] more than 1.30) were associated with a significantly higher mean patient survival time compared with that associated with euploid ANA. In contrast, the authors did not find this in either of the groups with AST and GBM. Recognizing six DNA histogram types (diploid, triploid, tetraploid, hyperdiploid, hypertriploid, and polymorphic), the authors observed that hypertriploid tumors were associated with greater patient survival compared with what happened in the cases of the five other DNA histogram types. This was true with respect to the three AST histopathologic types, Thus, DNA ploidy determination seemed helpful in characterizing aggressiveness in adult AST. Cancer 1992: 70:538‐546.

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DNA in human glioblastomas. A flow-fluorescence cytometrical examination of 96 tumors

Cited by 9 publications

References 65 publications

Growth of cultured human glioma tumour cells can be regulated with histamine and histamine antagonists

Growth of cultured human glioma tumour cells can be regulated with histamine and histamine antagonists

Prognostic significance of nuclear DNA content in human neuroepithelial tumors

Histopathologic grading and DNA ploidy in relation to survival among 206 adult astrocytic tumor patients

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