Immunohistochemical demonstration of DNA polymerase α in human brain-tumor cells

1990 ◽  
Vol 72 (2) ◽  
pp. 268-272 ◽  
Author(s):  
Katsuzo Kunishio ◽  
Nobuya Mishima ◽  
Takashi Matsuhisa ◽  
Kazuyuki Tsuno ◽  
Nobuhiko Matsumi ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Human Brain ◽  
Dna Polymerase ◽  
Ki 67 ◽  
Content Type ◽  
Brain Tumor Cells ◽  
Fine Print

✓ The proliferative capacity of brain-tumor cells was analyzed in vitro and in situ using monoclonal antibody (MAb) against deoxyribonucleic acid (DNA) polymerase α. For the in vitro studies, two cultured human glioma cell lines were investigated using MAb against DNA polymerase α, the MAb Ki-67, a serum against proliferating cell nuclear antigen (PCNA/cyclin), bromodeoxyuridine (BUdR), and an anti-BUdR MAb. During exponential growth of the cells, the percentage of polymerase α-positive cells (the “polymerase α score”) ranged from 72.0% to 77.1%, the Ki-67-positive cells (the “Ki-67 score”) ranged from 43.4% to 59.4%, the PCNA/cyclin-positive cells from 30.9% to 41.4%, and the BUdR labeling index from 28.6% to 39.3%. For the in situ studies, tissue from 60 human brain tumors and from two normal human brains was investigated and the polymerase α scores and Ki-67 scores were compared. In normal brain tissue, no immunostaining was found by either method. In brain tumors, both the polymerase α scores and the Ki-67 scores correlated with the histological grade of malignancy. Polymerase α scores were generally higher than Ki-67 scores in the same specimen, especially in malignant brain tumors. These findings suggest that immunostaining of DNA polymerase α is a convenient and important new method by which to estimate the cellular proliferation rate of brain tumors. Polymerase α scores may be closer to the growth fraction of the individual tumor than the MAb Ki-67 or other scores.

Assessment of brain tumor cell motility in vivo and in vitro

1995 ◽  
Vol 82 (4) ◽  
pp. 615-622 ◽  
Author(s):  
Michael R. Chicoine ◽  
Daniel L. Silbergeld
Keyword(s):  
Brain Tumor ◽  
Cell Motility ◽  
Human Brain Tumor ◽  
Content Type ◽  
Brain Tumor Cells ◽  
Tumor Cell Motility ◽  
Brain Tumor Cell ◽  
Fine Print

✓ Brain tumor dispersal far from bulk tumor contributes to and, in some instances, dominates disease progression. Three methods were used to characterize brain tumor cell motility in vivo and in vitro: 1) 2 weeks after implantation in rat cerebral cortex, single C6 cells labeled with a fluorescent tag had migrated to brain sites greater than 16 mm distant from bulk tumor; 2) time-lapse videomicroscopy of human brain tumor cells revealed motility of 12.5 µm/hr. Ruffling leading edges and pseudopod formation were most elaborate in more malignant cells; 3) an in vitro assay was devised to quantitatively evaluate motility from a region of high cell density to one of lower cell density. Human brain tumor cells were plated in the center of a petri dish, washed, and refed, establishing a 2-cm circular zone of cells in the dish center. Motility was determined by counting cells daily at predetermined distances from the central zone perimeter. Cells were found 1 cm from the perimeter by 24 hours and 3 cm from the perimeter by 4 days. Increasing serum concentration increased motility; however, neither fibronectin nor arrest of cells in the G0 phase by hydroxyurea altered motility. The addition of cytochalasin B to block cytoskeletal assembly prevented cell motility. Motility increased with increased malignancy. Subpopulations of cells were created by clonal amplification of cells that had migrated most rapidly to the dish periphery. Although morphologically indistinguishable when compared to the original cell line from which they were derived, these subpopulations demonstrated significantly increased motility.

Correlation of in vitro bromodeoxyuridine labeling index and DNA aneuploidy with survival or recurrence in brain-tumor patients

1990 ◽  
Vol 73 (3) ◽  
pp. 396-400 ◽  
Author(s):  
Takafumi Nishizaki ◽  
Tetsuji Orita ◽  
Koji Kajiwara ◽  
Norio Ikeda ◽  
Noboru Ohshita ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Survival Data ◽  
Patient Survival ◽  
Labeling Index ◽  
Content Type ◽  
Dna Aneuploidy ◽  
Labeling Method ◽  
Fine Print

✓ There are no previous reports correlating the in vitro bromodeoxyuridine (BUdR) labeling index (LI) with the clinical outcome in patients with brain tumors. The reliability of the LI as a predictor of patient survival or recurrence was examined in this study of 66 human brain tumors (19 gliomas, 18 meningiomas, and 29 others). Anti-BUdR staining was performed on surgically extirpated tumor tissue that had been treated with BUdR as previously described. Correlation of the BUdR LI with patient survival or tumor recurrence rate was carried out by the method of Kaplan and Meier. Deoxyribonucleic acid (DNA) aneuploidy was estimated in 52 cases. The results of this study indicate that BUdR LI values correlated well with the clinical course of patients with brain tumor. In comparison with patients with higher LI's, there was both a significantly higher survival rate for tumors other than meningiomas and a higher recurrence-free rate for meningiomas in patients with LI's of less than 4% and 1%, respectively. Although there was a tendency for patients without tumor aneuploidy to show better survival data than the others, no statistical difference was observed. These results suggest that the in vitro BUdR labeling method is reliable for prediction of a patient's prognosis, whereas prognosis on the basis of DNA aneuploidy alone is uncertain.

Prognostic factors in intracranial ependymomas in children

2000 ◽  
Vol 93 (4) ◽  
pp. 605-613 ◽  
Author(s):  
Dominique Figarella-Branger ◽  
Muriel Civatte ◽  
Corine Bouvier-Labit ◽  
Joany Gouvernet ◽  
Danielle Gambarelli ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Tumor Removal ◽  
Ki 67 ◽  
Content Type ◽  
Adjuvant Therapies ◽  
Endothelial Proliferation ◽  
Fine Print

Object. The occurrence of intracranial ependymomas in children is relatively infrequent, and their prognostic factors are still controversial, especially regarding histological composition.Methods. A retrospective study was conducted of 37 children treated during the last 20 years for intracranial ependymomas at the Hôpital de la Timone. Both univariate and multivariate statistical analyses were performed to assess the prognostic relevance of patient age and sex, extent of tumor removal, location of the tumor (supratentorial compared with infratentorial, median compared with lateral), tumor histological composition, and adjuvant therapies in affecting the 5-year progression-free survival (PFS) rate and overall survival (OS) rate. The following histopathological features, either alone or in combination, were analyzed: endothelial proliferation, necrosis, loss of differentiating structures (present compared with absent), the number of mitotic figures per 10 hpf, and cellularity (number of nuclei/5 hpf). In addition, immunohistochemical detection of Ki-67 antigen was performed and the Ki-67 labeling index (LI) evaluated in all cases.The 5-year OS and PFS rates were 45% and 25%, respectively (median follow up 34 months). Four patients died of disease without remission (median 163 days) and disease in 21 patients relapsed: 18 in situ and three both in situ and distantly. On univariate analysis total surgical resection and median infratentorial location were associated with a better outcome (p < 0.002) for both OS and PFS. Loss of differentiating structures was associated with poor prognosis (p < 0.008) and the combination of necrosis, endothelial proliferation, and mitotic index greater than 5 was also a negative predictive factor for both OS (p < 0.002) and PFS (p = 0.02). The PFS time was shorter in patients younger than 4 years of age and in patients in whom a Ki-67 LI greater than 1 was found (p = 0.03 and 0.006, respectively). Adjuvant radiotherapy and chemotherapy were not relevant to prognosis. Moreover, among the 15 patients in whom total excision was achieved, OS was better in those who did not receive adjuvant therapies. In contrast, adjuvant therapies significantly enhanced PFS time in patients in whom tumor excision was incomplete.Conclusions. This study and analysis of the literature further highlight that total tumor removal is the treatment of choice for ependymomas in children. Postoperative measurement of residual tumor is required, especially because a subgroup of patients might be treated by surgery alone. Median infratentorial ependymomas have to be distinguished from the lateral type. Appropriate and reproducible histological parameters and Ki-67 LI are of interest as predictors of outcome.

Immunobiology of primary intracranial tumors

1981 ◽  
Vol 54 (3) ◽  
pp. 331-337 ◽  
Author(s):  
William H. Brooks ◽  
Robert B. Latta ◽  
M. Stephen Mahaley ◽  
Thomas L. Roszman ◽  
Lynn Dudka ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Linear Combination ◽  
Tumor Recurrence ◽  
Intracranial Tumors ◽  
Content Type ◽  
Sequential Analyses ◽  
Fine Print ◽  
Host Immunocompetence

✓ Long-term assessment of general host immunocompetence of patients with primary malignant brain tumors indicates that although isolated determinations of nonspecific responsiveness are not clinically useful, sequential analyses utilizing a linear combination of in vitro lymphocyte probes are capable of predicting tumor recurrence prior to clinical deterioration.

Treatment of murine primary brain tumors with systemic interleukin-2 and tumor-infiltrating lymphocytes

1992 ◽  
Vol 76 (3) ◽  
pp. 513-519 ◽  
Author(s):  
Stephen C. Saris ◽  
Paul Spiess ◽  
Daniel M. Lieberman ◽  
Shan Lin ◽  
Stuart Walbridge ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Interleukin 2 ◽  
Tumor Infiltrating Lymphocytes ◽  
Similar Response ◽  
Content Type ◽  
Primary Brain Tumors ◽  
Infiltrating Lymphocytes ◽  
The Brain ◽  
Fine Print

✓ Methods have recently been described for the isolation and expansion of lymphocytes that have trafficked into animal and human tumors. These CD8-positive tumor-infiltrating lymphocytes (TIL's) have exceptional trafficking ability to, and efficacy against, tumor targets in extracranial sites. Prior to Phase I clinical trials for patients with gliomas, adoptive immunotherapy with TIL's was studied in a mouse model of primary brain tumors to determine if intracerebral tumors have a similar response. Glioma 261 (GL261) tumors were grown in the subcutaneous space of C57BL/6 mice. After enzymatic digestion, the cells were incubated in vitro with interleukin-2 (IL-2) until a confluent population of T lymphocytes was present. The in vitro efficacy of these TIL's was tested against fresh GL261 targets with a chromium release assay; the in vivo efficacy was tested against GL261 tumors in the liver and against irradiated and nonirradiated GL261 tumors in the brain. Mice received one of the following: intraperitoneal saline; intraperitoneal IL-2 (7500 to 50,000 U three times daily for 5 days); IL-2 plus intravenous TIL's (1 to 3 × 107 cells); 10 Gy cranial irradiation; irradiation plus IL-2; or irradiation plus IL-2 plus TIL's. The TIL preparation killed 77% of tumor targets in 4 hours at an effector:target ratio of 100:1. In animals with GL261 tumors in the liver, at 2 weeks there were 93 ± 37, 128 ± 45, and 21 ± 14 liver metastases in the control, IL-2, and IL-2 plus TIL groups, respectively. However, in animals with GL261 tumors in the brain, no treatment group had an increased survival rate compared to the control group. It is concluded that, although TIL and IL-2 immunotherapy can be used effectively to treat brain tumors in vitro and at sites outside the central nervous system, it is ineffective against the same type of tumor in the brain. Different methods of delivery or different combinations of these immunomodulators may be more effective; however, based on these findings, treatment of patients with IL-2 and TIL cannot be recommended until efficacy has been demonstrated in an animal model.

Stem cell studies of human malignant brain tumors

1985 ◽  
Vol 63 (3) ◽  
pp. 426-432 ◽  
Author(s):  
Bertrand Pertuiset ◽  
Dolores Dougherty ◽  
Carlos Cromeyer ◽  
Takao Hoshino ◽  
Mitchel Berger ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Brain Tumors ◽  
Tritiated Thymidine ◽  
Early Passage ◽  
Cell Cycle Time ◽  
Content Type ◽  
Cell Kill ◽  
Fine Print

✓ The proliferation kinetics were studied in early-passage cultures of cells from 13 human malignant brain tumors and two specimens of normal brain under conditions similar to those used in clonogenic cell-survival studies. Autoradiography was performed in all but four cases to estimate the fraction of cells actively replicating deoxyribonucleic acid (DNA), the approximate cell cycle time, and the effect of low-dose tritiated thymidine on cell proliferation. The mean tumor cell doubling time (TD) was 53 hours for five glioblastomas, 46 hours for two ependymomas, and 83 hours for two medulloblastomas. A gliosarcoma grew fastest (TD = 22 hours) in culture and a pilocytic astrocytoma grew slowest (TD = 144 hours). The approximate cell cycle time ranged from 1 to 2.5 days for all tumors tested. This suggests that chemotherapeutic agents that predominantly kill proliferating cells should be administered in vitro for at least 2 to 2.5 days to achieve maximum cell kill. The approximate growth fraction ranged from 0.65 to 0.96 for all tumors except for the two medulloblastomas and the pilocytic astrocytoma, which had growth fractions of 0.34 and 0.35, respectively. Most laboratories investigating the chemosensitivity of primary or early-passage human tumor cells require that 40% to 70% of cells be killed to consider a drug active in vitro. The results of this study suggest that the cell-cycle-specific agents cannot achieve a high enough cell kill to be considered active for some tumors that grow slowly in culture. An estimate of the in vitro growth rate is necessary to reliably interpret cell-survival results with such agents. Tritiated thymidine appeared to slow cell proliferation in some of the cultures, presumably as a result of radiation-induced DNA damage caused by tritium that had been incorporated into DNA. The degree to which cell growth was slowed in individual tumors correlated with the patient's clinical response to radiation therapy and postoperative survival time.

ATPase in human brain tumors

1970 ◽  
Vol 33 (2) ◽  
pp. 167-171 ◽  
Author(s):  
Edward R. Laws ◽  
John S. O'Connor
Keyword(s):  
Central Nervous System ◽  
Brain Tumors ◽  
Human Brain ◽  
Content Type ◽  
Human Brain Tumors ◽  
The Central Nervous System ◽  
Transport Atpases ◽  
Energy Dependent ◽  
And Control ◽  
Fine Print

✓ The energy-dependent membrane transport ATPases have been quantitatively determined in 59 human brain tumors and control cerebral cortex. The values for total ATPase were significantly decreased in the 11 types of brain tumors tested, while in the glioma group there was a consistent further decrease in ATPase with increasingly malignant types. The findings suggest that a deficiency in ATPase is a characteristic of neoplasia in the central nervous system.

Significance of hemorrhage into brain tumors: clinicopathological study

1987 ◽  
Vol 67 (6) ◽  
pp. 852-857 ◽  
Author(s):  
Douglas Kondziolka ◽  
Mark Bernstein ◽  
Lothar Resch ◽  
Charles H. Tator ◽  
J. F. Ross Fleming ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Tumor Type ◽  
Recurrent Tumor ◽  
Content Type ◽  
Intratumoral Hemorrhage ◽  
Clinicopathological Study ◽  
Pathological Review ◽  
Neurological Presentation ◽  
Fine Print

✓ A retrospective clinical and pathological review of 905 consecutive brain tumor cases (excluding pituitary adenoma and recurrent tumor) was conducted to identify cases in which intratumoral hemorrhage was confirmed grossly and/or pathologically. There were 132 cases so identified, for an overall tumor hemorrhage rate of 14.6%; of these, 5.4% were classified as macroscopic and 9.2% as microscopic. The presence of hemorrhage was correlated with the neurological presentation. The highest hemorrhage rate (70.0%) was found in patients with prior neurological history who experienced apoplectic deterioration (acute-on-chronic presentation). Only 57.1% of patients with acute deterioration in the absence of prior neurological symptoms had hemorrhages. The highest hemorrhage rate for primary brain tumors was 29.2% for mixed oligodendroglioma/astrocytoma, while the highest hemorrhage rate for any tumor type was 50% for metastatic melanoma. The clinical relevance of tumor hemorrhage is discussed.

Correlation of intraluminal thrombosis in brain tumor vessels with postoperative thrombotic complications: a preliminary report

1998 ◽  
Vol 89 (2) ◽  
pp. 200-205 ◽  
Author(s):  
Raul A. Rodas ◽  
Robert A. Fenstermaker ◽  
Paul E. McKeever ◽  
Mila Blaivas ◽  
Lawrence D. Dickinson ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Control Group ◽  
Neurosurgical Procedures ◽  
Tumor Vessels ◽  
Content Type ◽  
Prophylactic Measures ◽  
Depth Analysis ◽  
Thrombotic Complications ◽  
Fine Print

Object. Thrombotic complications (deep vein thrombosis and/or pulmonary embolization [DVT/PE]) occur in 18 to 50% of patients harboring brain tumors who undergo neurosurgical procedures. Such patients are at risk for DVT/PE because of immobility, paresis, hypovolemia, and lengthy surgery. The present study was undertaken to see whether tumor patients at highest risk for DVT/PE could be identified so that augmentation of prophylactic measures might be used to reduce the incidence of thrombotic complications. Methods. The authors conducted a retrospective analysis of 488 patients enrolled in their brain tumor registries between 1988 and 1995, identifying 57 patients (12%) with recorded symptomatic DVT, PE, or both postoperatively. In 24 of these 57 cases histological specimens were retrievable for review, allowing an in-depth analysis. Forty-five patients were lost to follow-up review, and the remaining 386 patients had no record of systemic thrombosis. Slides of pathological specimens were retrievable in 50 cases in which there was no DVT/PE. From these 50 cases, 25 were selected at random to represent the control group by a blinded observer. Seventeen (71%) of the 24 brain tumor specimens obtained in patients with DVT/PE stained positively for intraluminal thrombosis (ILT) after hematoxylin and eosin had been applied. The odds ratio associated with the presence of ILT was 17.8, with a confidence interval ranging from 4 to 79.3. No evidence of ILT was found in 22 patients (88%) within the control group (p < 0.0001, Fisher's exact test). Other factors that may predispose patients with brain tumors to DVT/PE—limb paresis, extent of tumor removal, and duration of the surgery—were also analyzed and found not to be statistically significant. Therefore, these factors were not the basis for differences seen between the study and control groups. Conclusions. These preliminary observations suggest that the presence of ILT within malignant glioma or glioblastoma tumor vessels may represent a marker of tumor-induced hypercoagulability.

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