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  • 1
    Electronic Resource
    Electronic Resource
    Primary intracranial neoplasms in the first year of life (1989)
    Springer
    Child's nervous system 5 (1989), S. 230-233 
    Details
    ISSN: 1433-0350
    Keywords: Infant brain tumor ; Astrocytoma ; Primitive neuroectodermal tumor ; Choroid plexus papilloma ; Radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Forty-one infants with histologically verified primary intracranial neoplasms were studied who had been diagnosed and treated during the first year of life at the Hospital for Sick Children during the years 1975–1986. Forty-one percent of tumors were astrocytomas, 22% were primitive neuroectodermal tumors, and 20% were choroid plexus papillomas. Seventy-one percent were located in the supratentorial compartment and 29% in the infratentorial compartment. Thirty percent were in the cerebral hemisphere, 12% in the optic pathway-hypothalamic region, 5% in the thalamus, 17% in the cerebellum, 5% in the brain stem, 12% in the lateral ventricles, 12% in the III ventricle, and 7% in the IV ventricle. The most common presenting features in this series of patients were vomiting and increasing head size. The symptoms and signs before diagnosis were present for 2 months or less in 87% of cases. Forty-four percent of the tumors were totally resected while only a partial resection or biopsy was carried out in 56%. Sixty-six percent of the patients required a CSF diversionary shunt. Twenty-nine percent of patients received radiotherapy. Slightly more than half of these received radiotherapy immediately after surgery, whereas delayed radiation therapy was performed in the remainder. The surgical mortality was 7.3%. Of the entire group, 39% have died, with most dying within 6 months of surgery. Treatment, survival relative to histologic type, psychomotor development, and neurologic function of the survivors are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271024
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  • 2
    Electronic Resource
    Electronic Resource
    Actinomycin D and staurosporine, potent apoptosis inducers in vitro, are potentially effective chemotherapeutic agents against glioblastoma multiforme (2000)
    Springer
    Cancer chemotherapy and pharmacology 45 (2000), S. 149-156 
    Details
    ISSN: 1432-0843
    Keywords: Key words Apoptosis ; Glioblastoma ; Caspase ; Actinomycin D ; Staurosporine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Although chemotherapeutic protocols that include chloroethylnitrosoureas (CENUs), such as 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), have been a mainstay of treatment for glioblastomas, the clinical outcomes have been unsatisfactory. More effective chemotherapeutic protocols for these tumors will require clear delineation of more cytocidal and cytostatic chemotherapeutic drugs. Methods and Results: In this study, we measured the cytocidal effects of ACNU, cisplatin, actinomycin D, and staurosporine, administered within their therapeutic dose ranges, in the treatment of glioblastoma cells. As assessed by WST-1 colorimetric assay, the number of viable cells decreased markedly in T98G cultures treated with actinomycin D or staurosporine, to less than 20% of the level in control cultures at 72 h, but did not decrease or even increased after 6 days of treatment with ACNU. After treatment with cisplatin for 5 days, cell viability decreased to 30% of control. As assessed by fluorescence microscopic examination of nuclear staining by Hoechst 33258 and by electron microscopy, the majority of dead cells treated with actinomycin D, staurosporine, or cisplatin had morphologic features of apoptosis. Caspase-3 activity increased more than 20-fold in cells treated with actinomycin D, staurosporine, or cisplatin but increased less than fivefold in ACNU-treated cells. In addition to caspase-3 activation, western blot analysis demonstrated cleavage of caspase-2 during the apoptotic process. These findings indicate that actinomycin D and staurosporine potently induce apoptosis, whereas ACNU exerts mainly a cytostatic rather than a cytocidal effect. Conclusion: Actinomycin D and staurosporine and their derivatives are potentially effective chemotherapeutic agents against glioblastoma cells at least in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050023
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  • 3
    Electronic Resource
    Electronic Resource
    Clinical and histopathological analysis of proliferative potentials of recurrent and non-recurrent meningiomas (1996)
    Springer
    Acta neuropathologica 91 (1996), S. 504-510 
    Details
    ISSN: 1432-0533
    Keywords: Key words Meningioma ; MIB-1 ; Ki-67 ; Proliferative ; potential ; Recurrence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Proliferative potentials of meningiomas from 127 patients were examined immunohistochemically using the anti-Ki-67 monoclonal antibody, MIB-1, on paraffin sections, and the correlation among MIB-1 staining index (SI), histopathological finding, and clinial course of the disease was analyzed retrospectively. The mean MIB-1 SI of 50 male patients with meningioma was 5.5%, whereas that of 77 female patients was 2.7%. Higher MIB-1 SI were observed for younger patients. These age- and sex-related differences in MIB-1 SI were statistically significant. The patients were assigned to one of three groups: those with non-recurrent meningioma (n = 73); those with recurrent meningioma in whom the specimens obtained during the initial surgery were used to calculate the MIB-1 SI (n = 21); and those with recurrent meningioma for whom the specimens obtained during the surgery for recurrent tumors were used to calculate the MIB-1 SI (n = 33). The mean MIB-1 SI in these patients were 1.6%, 3.6%, and 8.8%, respectively, and there were statistically significant differences among these three groups. Statistical analyses reveal that meningiomas with a MIB-1 SI of 3% or more have a significantly high tendency for recurrence during the clinical courses, especially within the first 10-year follow-up periods. Moreover, there is statistically significant correlation between MIB-1 SI and recurrence in each Simpson’s grade. The time interval to the next recurrence for recurrent meningiomas is associated with the proliferative potential represented by the MIB-1 SI, and a correlation equation has been proposed to predict the date of the next recurrence. Analyses on cellularity of meningiomas revealed no statistically significant difference in cellularity between non-recurrent and recurrent meningiomas. There was no statistically significant relationship between cellularity and MIB-1 SI of meningiomas. In conclusion, examination on proliferative potentials of meningiomas using MIB-1 SI is very important for biological and histopathologicl analyses and the prediction of future recurrence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050458
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  • 4
    Electronic Resource
    Electronic Resource
    Heparin-binding epidermal growth factor-like growth factor stimulates mitogenic signaling and is highly expressed in human malignant gliomas (1998)
    Springer
    Acta neuropathologica 96 (1998), S. 322-328 
    Details
    ISSN: 1432-0533
    Keywords: Key words Heparin-binding epidermal growth ; factor-like growth factor ; Autocrine ; Juxtacrine ; Glioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We previously reported that schwannoma-derived growth factor (SDGF), a member of heparin-binding epidermal growth factor (EGF) family, participates in autocrine pathways and promotes rat glioma cell growth. To investigate the potential role of similar molecules in human gliomas, we examined 7 human glioma cell lines and 11 glioblastoma specimens for expression of the human homologue of SDGF, amphiregulin (AR), as well as heparin-binding EGF-like growth factor (HB-EGF). Northern blot analysis revealed that only one cell line and no tumor specimens expressed AR mRNA. In contrast, HB-EGF mRNA was expressed in all human glioma cell lines and its level of expression was two- to five-fold higher than that of control brain tissues in 8 of 11 glioblastoma cases. Immunohistochemistry demonstrated that membrane-anchored HB-EGF (proHB-EGF) and EGFR were co-expressed in 44% of 34 human malignant gliomas. Introduction of exogenous HB-EGF (10 ng/ml) increased human glioma cell proliferation, and anti-HB-EGF blocking antibodies reduced the growth of glioma cells by 30–40%, confirming the presence of an autocrine loop. When added to the medium, transforming growth factor-α, basic fibroblast growth factor, or HB-EGF rapidly induced HB-EGF mRNA expression. These results indicate that HB-EGF and proHB-EGF contribute to the growth of human malignant glioma cells, most likely through autocrine and juxtacrine mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050901
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  • 5
    Electronic Resource
    Electronic Resource
    Spontaneous Regression of a Residual Pineal Tumor after Resection of a Cerebellar Vermian Germinoma (1999)
    Springer
    Journal of neuro-oncology 41 (1999), S. 65-70 
    Details
    ISSN: 1573-7373
    Keywords: germinoma ; spontaneous regression ; multiple intracranial ; germ cell tumor ; immunological mechanism ; apoptosis ; MIB-1 index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A case of multiple intracranial germ cell tumor in which a pineal tumor regressed spontaneously after resection of the cerebellar mass is reported. Immunohistochemical staining of the cerebellar mass showed that most of the infiltrating lymphocytes were positive for CD3 and CD8. The anti-Ki-67 monoclonal antibody MIB-1 staining of the resected tumor revealed a high MIB-1 positivity ratio (36.1%) among the large tumor cells, and TUNEL staining demonstrated that positivity in up to 6% of the tumor cells. Possible mechanisms responsible for this spontaneous regression including immunological responses and apoptosis induced by T lymphocytes are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006155120191
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  • 6
    Electronic Resource
    Electronic Resource
    Radiation therapy combined with radiosensitizing agents for cerebral glioblastoma in adults (1994)
    Springer
    Journal of neuro-oncology 19 (1994), S. 227-237 
    Details
    ISSN: 1573-7373
    Keywords: glioblastoma ; brain tumor ; radiation therapy ; chemotherapy ; ACNU
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We analyzed our treatment results of 71 operated patients with cerebral glioblastoma treated by conventional external radiation therapy (mean dose 60.2 Gy) combined with radiosensitizing agents. More than 50% reduction of tumor volume was obtained in 20 patients (28.2%). A response rate of at least 40% was obtained in patients treated with combined ACNU-vincristine-nicardipine, ACNU-5FU-hydroxyurea, or cisplatin alone. The combination of ACNU and vincristine with or without nicardipine resulted in significantly longer survival. The median survival in this group was 101.1 weeks and the two-year survival rate was 45.9%; these results were significantly better than those achieved with other ACNU combinations or other combinations without ACNU. In the analysis of survival, factors correlated to longer survival were a patient age of younger than 45 years, wide resection of the tumor, a good postoperative performance status (KS ≥70%), a radiation dose of 68–72 Gy, small postoperative tumor remnants (〈 20 cm3), no visible tumor after radiation therapy, and the administration of adjuvant chemotherapy. Maximum resection of the tumor and localized irradiation with a dose of 70 Gy combined with ACNU and vincristine appears to be the most effective treatment at present.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01053276
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  • 7
    Electronic Resource
    Electronic Resource
    Negative effects of wild-type p53 and s-Myc on cellular growth and tumorigenicity of glioma cells (1994)
    Springer
    Journal of neuro-oncology 19 (1994), S. 259-268 
    Details
    ISSN: 1573-7373
    Keywords: s-myc gene ; p53 ; gene transfection ; tumor suppressor gene ; cell cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human (U251, U87, U343) and rat glioma cell lines (C6, 9L) were examined by the reverse transcriptase-polymerase chain reaction and subsequent nucleotide sequencing analysis to see whether they express wild type (wt)-p53 or mutated form (mut)-p53 messages. Results showed that U87, U343, and C6 cells expressed wt-p53 messages whereas U251 and 9L cells expressed mut-p53 messages. All these cell lines were transfected with wt-p53 cDNA or the s-myc gene linked to the mouse mammary tumor virus (MMTV) promoter. Of several G418-resistant clones obtained from each transfection, a few expressed the s-Myc or wt-p53 proteins. Independent of mutations in the intrinsic p53 gene, the cellular growthin vitro and tumorigenicity in nude mice of these clones were drastically suppressed, the extent of suppression being correlated with the expression level of the transfected gene. Flow-cytometric analysis demonstrated that both p53 and s-Myc arrested the cell cycle at the G1/S boundary. These data suggest that these genes having negative effects on tumor cell proliferation could be used in gene therapy of gliomas, which are caused by alteration of the p53 gene or by some other genetic change.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01053280
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  • 8
    Electronic Resource
    Electronic Resource
    Proliferative activity of central neurocytoma: Measurement of tumor volume doubling time, MIB-1 staining index and bromodeoxyuridine labeling index (1997)
    Springer
    Journal of neuro-oncology 32 (1997), S. 103-109 
    Details
    ISSN: 1573-7373
    Keywords: central neurocytoma ; MIB-1 ; bromodeoxyuridine labeling index (BUdR LI ; BrdU LI) ; tumor volume doubling time (Td) ; radiation therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Central neurocytoma is considered to be a benign intracranial neoplasm, but little is known about the biological behavior of this type of tumor.Proliferative activity of central neurocytoma was measured in 10 cases using MIB-1 staining for Ki-67 antigen.The MIB-1 staining value varied from 〈 0.1% to 5.6%, to indicating that some of these tumors have proliferative potential similar to that of anaplastic astrocytoma or malignant meningioma. Thebromodeoxyuridine labeling index (BUdR LI, BrdU LI) was measured in 2 cases and the results correlated well with those of the MIB-1 analysis. Tumor volume doubling time (Td) measured in one case was 358 days which is similar to that of malignant meningioma.In one case, the MIB-1 value taken beforeand after 58 Gy of radiation treatment decreased markedly from 5.6%to 0.2%. The other 9 cases were also treated by radiation therapy (50—60 Gy) and no tumor recurrence was observed during follow-up periods ranging from 23 to 160 months. Another two patients with partially removed and 3 with subtotallyremoved tumors showing relatively high MIB-1 values might also have benefited from radiation therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005740205113
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  • 9
    Electronic Resource
    Electronic Resource
    Predicting the recurrence of ependymomas from the bromodeoxyuridine labeling index (1992)
    Springer
    Child's nervous system 8 (1992), S. 273-278 
    Details
    ISSN: 1433-0350
    Keywords: Brain tumor ; Ependymoma ; Bromodeoxyuridine ; Recurrence ; Proliferative potential ; Labeling index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The usefulness of histopathological grading in predicting the prognosis of patients with ependymomas is controversial. To clarify the discrepancy between the histological malignancy and the prognosis of these tumors, we estimated the proliferative potential of 32 intracranial and intraspinal ependymomas and correlated the findings with the clinical behavior. Each patient received an intraoperative infusion of bromodeoxyuridine (BUdR, 200 mg/m2 i.v.) before tumor removal; the BUdR labeling index (LI), or percentage of BUdR-labeled cells, was determined immunohistochemically in excised specimens. The mean BUdR LI (±SD) of intracranial malignant ependymomas was 4.1±2.8%. Nonmalignant intracranial and intraspinal ependymomas and subependymomas had mean LIs of 1.5±0.9%, 1.1±0.3%, and 〈1%, respectively. Overall, 44% of the tumors recurred. There were no statistically significant differences in the recurrence rates of intracranial and intraspinal ependymomas, including subependymomas (43% and 44%, respectively), or of intracranial ependymomas with LIs greater than 1.0% and less than 1.0% (67% and 44%, respectively). However, the early recurrence rate (within 24 months after treatment) of tumors with LIs greater than 1.0% was higher than that of tumors with LIs of less than 1.0% (100% vs. 25%, P〈0.05). The BUdR LI also showed a statistically significant inverse correlation with the time to recurrence. These findings indicate that BUdR LI reflects the proliferative potential of individual ependymomas and can be used to help predict the recurrence and estimate the prognosis of these tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00300795
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