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.

The long-term side effects of radiation therapy for benign brain tumors in adults

1990 ◽  
Vol 73 (4) ◽  
pp. 502-512 ◽  
Author(s):  
Ossama Al-Mefty ◽  
Jane E. Kersh ◽  
Anupam Routh ◽  
Robert R. Smith
Keyword(s):  
Radiation Therapy ◽  
Side Effects ◽  
Brain Tumors ◽  
Adult Patients ◽  
Intracranial Tumors ◽  
Content Type ◽  
Pituitary Dysfunction ◽  
Fine Print

✓ Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors (two of these also had pituitary dysfunction). One clival tumor, with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered “safe” treatment for benign brain tumors.

The deposition of Hg203-chlormerodrin in experimental brain tumors

1971 ◽  
Vol 35 (3) ◽  
pp. 303-308 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Louis Bakay ◽  
Joseph C. Lee
Keyword(s):  
Brain Tumors ◽  
Tumor Cells ◽  
Normal Brain ◽  
Intracranial Tumors ◽  
Electron Microscopic ◽  
Electron Microscopic Autoradiography ◽  
Content Type ◽  
Meningeal Tumors ◽  
Vacuolar System ◽  
Fine Print

✓ The deposition of Hg203-chlormerodrin was studied in intracranial tumors in mice induced by implantation of 20-methyl cholanthrene by tissue assay, as well as light microscopic and electron microscopic autoradiography. The investigations were carried out in astrocytomas, glioblastomas, and meningeal tumors. The chlormerodrin content of the tumors exceeded that of normal brain with a significant tumor/brain ratio ranging from 5.8 to 22.5. It was found that the chlormerodrin molecule becomes rapidly incorporated in the tumor cells, with a preference for that portion of the cytoplasm associated with the vacuolar system.

Multiple meningiomas: a long-term review

1983 ◽  
Vol 59 (1) ◽  
pp. 1-5 ◽  
Author(s):  
John P. Sheehy ◽  
H. Alan Crockard
Keyword(s):  
Tumor Recurrence ◽  
The Other ◽  
Von Recklinghausen’S Disease ◽  
Von Recklinghausen's Disease ◽  
Content Type ◽  
Multiple Meningiomas ◽  
Recklinghausen's Disease ◽  
Fine Print ◽  
Recklinghausen’S Disease

✓ Ten cases of multiple meningiomas seen over a 34-year period have been reviewed. The total case load from which these cases were selected was 566. The incidence of multiple meningiomas found prior to the introduction of computerized tomography (CT) in this series was 1.1%. The incidence since the introduction of CT was 8%. In eight cases all the tumors were found at the initial presentation and surgery; in the other two cases new tumors were discovered 1 and 4 years later. In only one case was von Recklinghausen's disease known to be present, and this patient developed new tumors. Six cases have been followed for 5 or more years, two for 16 years. Tumor recurrence has not been seen. All the patients were females. There was a higher proportion than usual of the whorling psammomatous type of tumor; papillary, angioblastic or malignant forms were not noted. The possibility of multiple meningiomas being a forme fruste of von Recklinghausen's disease is considered.

Immunobiology of primary intracranial tumors

1977 ◽  
Vol 47 (6) ◽  
pp. 871-885 ◽  
Author(s):  
Ronald E. Woosley ◽  
M. Stephen Mahaley ◽  
Jane L. Mahaley ◽  
Gary M. Miller ◽  
William H. Brooks
Keyword(s):  
Effector Cell ◽  
Intracranial Tumors ◽  
Content Type ◽  
Postoperative Course ◽  
Immune Parameters ◽  
Relationship Of ◽  
The Relationship ◽  
Cytotoxic Responses ◽  
Fine Print

✓ Fifty-six in vitro microcytotoxicity assays were conducted on 30 patients with intracranial tumors at various times during their postoperative course. Significant specific cellular cytotoxic responses were found in nine of 56 assays, humoral cytotoxic responses in nine of 54 assays, and host effector cell-dependent, antibody-dependent cytotoxic responses in four of 28 assays. Variables that might influence the occurrence of cytotoxicity were studied, and the relationship of these findings to other immune parameters was discussed.

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.

Production of collagenase and inhibitor (TIMP) by intracranial tumors and dura in vitro

1983 ◽  
Vol 59 (3) ◽  
pp. 461-466 ◽  
Author(s):  
Ahmed N. Halaka ◽  
Rowena A.D. Bunning ◽  
Colin C. Bird ◽  
Myles Gibson ◽  
John J. Reynolds
Keyword(s):  
Organ Culture ◽  
Tumor Invasion ◽  
Culture Media ◽  
Intracranial Tumors ◽  
Short Term ◽  
Content Type ◽  
Collagenase Inhibitor ◽  
Tissue Degradation ◽  
Fine Print

✓ The production of collagenase and collagenase inhibitor (TIMP) by various intracranial tumors (25 meningiomas, eight gliomas, seven metastases, four pituitary adenomas, and five others) was studied in short-term organ culture. While meningiomas produced negligible amounts of collagenase, two metastatic carcinomas of bronchial and breast origin produced significant amounts of the enzyme. Cultures of dura from an invasive meningioma and of bone invaded by a meningioma also produced collagenase. In varying amounts, TIMP was detected in culture media from most of the tumors studied; invasive tumors tended to produce less TIMP than noninvasive tumors. The results are discussed in relation to current views on tissue degradation and mechanisms of tumor invasion.

Selective opening of the blood—brain barrier by a nitric oxide donor and long-term survival in rats with C6 gliomas

2003 ◽  
Vol 99 (4) ◽  
pp. 728-737 ◽  
Author(s):  
Astrid Weyerbrock ◽  
Stuart Walbridge ◽  
Ryszard M. Pluta ◽  
Joseph E. Saavedra ◽  
Larry K. Keefer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carotid Artery ◽  
Brain Tumors ◽  
Internal Carotid Artery ◽  
Internal Carotid ◽  
Term Survival ◽  
Content Type ◽  
Tumor Selective ◽  
Fine Print

Object. The response of brain tumors to systemic chemotherapy is limited by the blood—tumor barrier (BTB). Nitric oxide (NO) has been implicated in the regulation of vascular permeability and blood flow. The authors evaluated the effects of exogenous NO, which was released from a short-acting NO donor (Proli/NO), and those of NO metabolites on the capillary permeability of tumors and normal brain tissue by using quantitative autoradiography in a C6 glioma model in rats. Methods. The Proli/NO was infused at a wide dose range (10−2 to 10−12 M) either intravenously or into the internal carotid artery (ICA) and demonstrated substantial tumor-selective increases in blood-brain barrier (BBB) permeability in response to various-sized tracers ([14C]aminoisobutyric acid, [14C]sucrose, [14C]dextran). Internal carotid artery or intravenous administration of sodium nitrite had a comparable effect on BTB permeability. The NO effect on microvascular permeability could be obtained without causing hemodynamic side effects. The effect of NO on the efficacy of carboplatin chemotherapy was investigated in intracerebral C6 gliomas. Simultaneous intravenous infusions of Proli/NO (10−6 M) and carboplatin (20 mg/kg) led to long-term survival in 40% of rats harboring intracerebral C6 gliomas compared with control animals receiving ICA or intravenous infusions of carboplatin, Proli/NO, or vehicle alone. No residual tumor was demonstrated on histological or magnetic resonance imaging studies performed in rats treated with Proli/NO and carboplatin, and no toxicity was observed. Conclusions. This new approach demonstrated the in vivo efficacy and safety of NO and nitrite in enhancing the delivery of systemically delivered radiolabeled tracers and carboplatin into rat gliomas. The NO-induced tumor-selective BBB disruption and intravenous carboplatin chemotherapy may be more efficacious than current chemotherapy strategies against brain tumors.

Benign cerebellar astrocytomas in children

1999 ◽  
Vol 90 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Philippe Pencalet ◽  
Wirginia Maixner ◽  
Christian Sainte-Rose ◽  
Arielle Lellouch-Tubiana ◽  
Giuseppe Cinalli ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Tumor Recurrence ◽  
Surgical Excision ◽  
Benign Tumors ◽  
Transitional Form ◽  
Duration Of Symptoms ◽  
Content Type ◽  
Fine Print

Object. Cerebellar astrocytomas are benign tumors of childhood known to be associated with excellent long-term survival in patients in whom complete surgical resection is possible. However, the roles of other factors—clinical, radiological, histological, and therapeutic—in the survival of the patient, tumor recurrence, and long-term patient outcome remain imprecise. The goal of this study was to examine these factors and their relationships.Methods. To clarify these issues a retrospective review was conducted of 168 children who were surgically treated for a cerebellar astrocytoma at Hôpital Necker—Enfants Malades between 1955 and 1995. These patients' clinical files were examined, the histological characteristics of their tumors were reviewed, and their outcomes were assessed according to Bloom's scale and the Wechsler intelligence quotient test.Of the 168 patients in the study, 91 were male and 77 were female with a mean age of 6.9 years and a mean follow up lasting 7.7 years. Tumors were identified as being strictly located in the cerebellum in 76.2% of the patients and as involving the brainstem (referred to as the “transitional form”) in 23.8% of the patients. Complete surgical excision was possible in 88.7% of cases. There was a total mortality rate of 4.2% and a tumor recurrence rate of 9.5%. Fifty-eight percent of the patients had no neurological sequelae at follow-up evaluation.Pejorative factors that were discovered by multivariate analysis to be important included: a long preoperative duration of symptoms and the transitional form of tumor with respect to survival; incomplete tumor excision with respect to an increased risk of recurrence; and a long preoperative duration of symptoms, an early epoch during which surgery was performed (1955–1974), severe ventricular dilation, and the transitional form of tumor with respect to a poorer long-term patient outcome.Conclusions. The presence of brainstem involvement (tumor in the transitional form) emerged as a significant negative prognostic factor and should be treated as a distinct nosological entity. The extent of surgical excision has a significant bearing on the risk of tumor recurrence.

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.

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