Acute nonlymphocytic leukemia following treatment of malignant glioma

1984 ◽  
Vol 60 (6) ◽  
pp. 1287-1290 ◽  
Author(s):  
Sanford Kempin ◽  
Narayan Sundaresan ◽  
William B. Shapiro ◽  
Zalmen Arlin
Keyword(s):  
Brain Tumors ◽  
Combined Modality Treatment ◽  
Acute Nonlymphocytic Leukemia ◽  
Review Of The Literature ◽  
Tumor Treatment ◽  
Content Type ◽  
Malignant Brain Tumors ◽  
Tumor Survival ◽  
The Brain ◽  
Fine Print

✓ Two patients with malignant brain tumors who developed acute nonlymphocytic leukemia after treatment with radiation and chemotherapy are described. Both patients survived more than 2 years after diagnosis of the brain tumor. Survival following the diagnosis of leukemia was short, and both patients died of hemorrhage secondary to thrombocytopenia. A review of the literature reveals that leukemia after combined-modality treatment of malignant brain tumors is rare. A prolonged survival period from diagnosis of the primary tumor, treatment with nitrosoureas and radiation, plus the development of a preleukemic myelodysplastic syndrome are all important features of therapy-related nonlymphocytic leukemia.

Thymidine kinase-mediated killing of rat brain tumors

1993 ◽  
Vol 79 (5) ◽  
pp. 729-735 ◽  
Author(s):  
David Barba ◽  
Joseph Hardin ◽  
Jasodhara Ray ◽  
Fred H. Gage
Keyword(s):  
Gene Therapy ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Wild Type ◽  
Cns Disorders ◽  
Content Type ◽  
Potential Applications ◽  
Ganciclovir Treatment ◽  
The Brain ◽  
Fine Print

✓ Gene therapy has many potential applications in central nervous system (CNS) disorders, including the selective killing of tumor cells in the brain. A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir. The HSV-TK gene was introduced in vitro into tumor cells (C6-TK and 9L-TK), then these modified tumor cells were evaluated for their sensitivity to cell killing by ganciclovir. In a dose-response assay, both C6-TK and 9L-TK cells were 100 times more sensitive to killing by ganciclovir (median lethal dose: C6-TK, 0.1 µg ganciclovir/ml; C6, 5.0 µg ganciclovir/ml) than unmodified wild-type tumor cells or cultured fibroblasts. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to kill established brain tumors in rats as quantified by both stereological assessment of brain tumor volumes and studies of animal survival over 90 days. Rats with brain tumors established by intracerebral injection of wild-type or HSV-TK modified tumor cells or by a combination of wild-type and HSV-TK-modified cells were studied with and without ganciclovir treatments. Stereological methods determined that ganciclovir treatment eliminated tumors composed of HSV-TK-modified cells while control tumors grew as expected (p < 0.001). In survival studies, all 10 rats with 9L-TK tumors treated with ganciclovir survived 90 days while all untreated rats died within 25 days. Curiously, tumors composed of combinations of 9L and 9L-TK cells could be eliminated by ganciclovir treatments even when only one-half of the tumor cells carried the HSV-TK gene. While not completely understood, this additional tumor cell killing appears to be both tumor selective and local in nature. It is concluded that HSV-TK gene therapy with ganciclovir treatment does selectively kill tumor cells in the brain and has many potential applications in CNS disorders, including the treatment of cancer.

Site-specific immune response to implanted gliomas

2001 ◽  
Vol 95 (6) ◽  
pp. 1012-1019 ◽  
Author(s):  
Martin A. Proescholdt ◽  
Marsha J. Merrill ◽  
Barbara Ikejiri ◽  
Stuart Walbridge ◽  
Aytac Akbasak ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Tumor Growth ◽  
Mhc Class Ii ◽  
Lymphocytic Infiltration ◽  
Class Ii ◽  
Content Type ◽  
Time Points ◽  
Early Tumor ◽  
The Brain ◽  
Fine Print

Object. Immunotherapy for glioblastoma has been uniformly ineffective. The immunological environment of the brain, with its low expression of major histocompatibility complex (MHC) molecules and limited access for inflammatory cells and humoral immune effectors due to the blood—brain barrier (BBB), may contribute to the failure of immunotherapy. The authors hypothesize that brain tumors are protected from immune surveillance by an intact BBB at early stages of development. To investigate the immunological characteristics of early tumor growth, the authors compared the host response to a glioma implanted into the brain and into subcutaneous tissue. Methods. Samples of tumors growing in the brain or subcutaneously in rats were obtained for 7 consecutive days and were examined immunohistochemically for MHC Class I & II molecules, and for CD4 and CD8 lymphocyte markers. Additionally, B7-1 costimulatory molecule expression and lymphocyte-specific apoptosis were examined. Conclusions. On Days 3 and 4 after implantation, brain tumors displayed significantly lower MHC Class II expression and lymphocytic infiltration (p < 0.05). After Day 5, however, no differences were detected. The MHC Class II expressing cells within the brain tumors appeared to be infiltrating microglia. Minimal B7-1 expression combined with lymphocyte-specific apoptosis were detected in both brain and subcutaneous tumors. Low MHC Class II expression and low lymphocytic infiltration at early time points indicate the importance of the immunologically privileged status of the brain during early tumor growth. These characteristics disappeared at later time points, possibly because the increasing perturbation of the BBB alters the specific immunological environment of the brain. The lack of B7-1 expression combined with lymphocyte apoptosis indicates clonal anergy of glioma-infiltrating lymphocytes regardless of implantation site.

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.

Uptake of tritiated methotrexate by mouse brain tumors after intravenous or intrathecal administration

1974 ◽  
Vol 40 (6) ◽  
pp. 706-716 ◽  
Author(s):  
Yukitaka Ushio ◽  
Toru Hayakawa ◽  
Heitaro Mogami
Keyword(s):  
Brain Tumors ◽  
Brain Tissue ◽  
Intravenous Injection ◽  
Malignant Gliomas ◽  
Intrathecal Administration ◽  
Drug Dosage ◽  
Content Type ◽  
Radioactive Assay ◽  
The Brain ◽  
Fine Print

✓ Malignant gliomas were induced in strain ddN mice by intracerebral implantation of a 20-methylcholanthrene pellet. The uptake and distribution of tritiated methotrexate (MTX-3H) in the tumor were investigated by radioactive assay and radioautography after single intravenous or intrathecal injections. By either route, a large amount of MTX-3H was taken up by gliomas, and a significantly higher concentration was observed in tumor than in the brain tissue. At 24 hours after intrathecal administration, the uptake of MTX-3H by gliomas exceeded that achieved after intravenous injection, although the drug dosage in the latter was 10 times that in the former.

Thiamine-deficient lactic acidosis with brain tumor treatment

1998 ◽  
Vol 89 (6) ◽  
pp. 1025-1028 ◽  
Author(s):  
Hiroshi Kuba ◽  
Takanori Inamura ◽  
Kiyonobu Ikezaki ◽  
Masatou Kawashima ◽  
Masashi Fukui
Keyword(s):  
Brain Tumor ◽  
Lactic Acidosis ◽  
Brain Tumors ◽  
Neurological Deficits ◽  
High Dose ◽  
Content Type ◽  
Malignant Brain Tumors ◽  
Level Of Consciousness ◽  
Lactic Acidemia ◽  
Fine Print

✓ Lactic acidosis due to thiamine deficiency is known to complicate chemotherapy and radiotherapy treatment of malignant extracranial tumors, but to the authors' knowledge, this complication has not been reported in patients treated for malignant brain tumors. They report three such cases, demonstrating that this complication can occur during treatment of brain tumors. In all patients, consciousness levels deteriorated within 1 to 2 days. Serum lactic acid levels increased to concentrations between 62 and 96.7 mg/dl, resulting in severe metabolic acidosis. A low blood thiamine level (9 ng/ml) was demonstrated at the onset in one case, and high-dose thiamine infusions dramatically improved lactic acidemia as well as impairment of consciousness in two cases. In the other case, hydrocephalus was suspected initially, resulting in a delay in thiamine supplementation. Clinical differentiation of this form of lactic acidosis from hydrocephalus or tumor progression can be very difficult in a patient undergoing treatment for a malignant brain tumor. Demand for thiamine is thought to be increased in patients with malignant brain tumors, and supplemental thiamine during treatment is necessary to prevent lactic acidosis. When this complication occurs, immediate treatment with sufficient thiamine is essential, together with normalization of pH by using sodium bicarbonate. With timely intervention, the level of consciousness can recover to the preacidotic state with no new neurological deficits.

Focal histiocytosis X of the parietal lobe

1980 ◽  
Vol 52 (3) ◽  
pp. 431-433 ◽  
Author(s):  
Arfa Khan ◽  
John D. Fulco ◽  
Ashok Shende ◽  
Alan Rosenthal ◽  
Joseph A. Marc
Keyword(s):  
Computerized Tomography ◽  
Parietal Lobe ◽  
Histiocytosis X ◽  
Review Of The Literature ◽  
Content Type ◽  
The Brain ◽  
Tomography Scan ◽  
Space Occupying Lesion ◽  
Fine Print

✓ The authors describe a case of histiocytosis X of the parietal lobe presenting as a space-occupying lesion on a computerized tomography scan of the brain. The clinical, radiographic, and therapeutic aspects of the case are discussed. A brief review of the literature is presented.

Brain-tumor imaging using radiopaque perfluorocarbon

1983 ◽  
Vol 58 (5) ◽  
pp. 650-653 ◽  
Author(s):  
Nicholas J. Patronas ◽  
Javad Hekmatpanah ◽  
Kunio Doi
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Contrast Agent ◽  
Contrast Medium ◽  
Computerized Tomography ◽  
Tumor Imaging ◽  
Content Type ◽  
X Ray ◽  
The Brain ◽  
Fine Print

✓ Perfluorocarbon, a new tumor-seeking x-ray contrast agent, was injected into three rats with experimental brain tumors. After 1 to 3 days the rats were sacrificed, and the brains were removed and subjected to x-ray study. All showed dense radiopaque areas which correlated with the size and shape of the corresponding brain tumors. Conversely, none of the radiograms taken of the brain tumor in five rats receiving no perfluorocarbon (control animals) showed similar increased density. These findings suggest that perfluorocarbon may serve a useful role as a contrast medium for computerized tomography studies of brain tumors in man.

Transcriptional expression of survivin and its splice variants in brain tumors in humans

2003 ◽  
Vol 99 (4) ◽  
pp. 738-745 ◽  
Author(s):  
Yoshitaka Yamada ◽  
Toshihiko Kuroiwa ◽  
Toshimasa Nakagawa ◽  
Yoshinaga Kajimoto ◽  
Takehiko Dohi ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Tumor Cell ◽  
Cell Lines ◽  
Splice Variants ◽  
Expression Patterns ◽  
Tumor Cell Lines ◽  
Content Type ◽  
Malignant Brain Tumors ◽  
Fine Print

Object. Survivin, one of the apoptosis inhibitor proteins, has been detected in most cancers in humans. In addition, two splice variants (survivin-2B and survivin-ΔEx3) have been identified. The authors investigated the transcription levels of survivin messenger (m)RNA and its splice variants in nine tumor cell lines, including gliomas, and in 25 brain tumor samples, by performing quantitative reverse transcription-polymerase chain reaction. The correlation between transcript expression levels and pathological findings were also analyzed. Methods. Transcription levels were measured using primer pairs specific for survivin and either of its splice variants and were normalized to the glyceraldehyde 6-phosphate dehydrogenase. Among the tumor cell lines tested, glioblastoma cell lines showed the highest levels of survivin expression. Among brain tumor samples studied, survivin was preferentially expressed in malignant brain tumors and gliomas. The relative expression level of survivin-ΔEx3/survivin was significantly higher in malignant than in benign brain tumor samples. Expression patterns were dominant for survivin-ΔEx3 in malignant brain tumors and dominant for survivin-2B in benign ones. A significant linear correlation between survivin mRNA expression and MIB-1 labeling index was demonstrated in all brain tumor samples. Conclusions. The authors' results indicate that quantifying the levels of survivin and its splice variants is useful for the prediction of the cell biological malignancy of gliomas, independent of their pathological features.

Ganglioglioma of the brain stem

1984 ◽  
Vol 60 (2) ◽  
pp. 431-434 ◽  
Author(s):  
Carlos A. Garcia ◽  
Paul A. McGarry ◽  
Mauricio Collada
Keyword(s):  
Brain Stem ◽  
Clinical Improvement ◽  
Partial Resection ◽  
Prolonged Survival ◽  
Review Of The Literature ◽  
Content Type ◽  
The Brain ◽  
Fine Print

✓ A case of brain-stem ganglioglioma is reported. A review of the literature revealed only 13 other reported cases. Brain-stem gangliogliomas usually become symptomatic in the first and second decades of life and involve the medulla and pons. Clinical improvement and prolonged survival have been reported after partial resection.

Neonatal intracranial choriocarcinoma

1971 ◽  
Vol 35 (4) ◽  
pp. 465-471 ◽  
Author(s):  
David L. Kelly ◽  
Jack Kushner ◽  
William T. McLean
Keyword(s):  
Contrast Medium ◽  
Clinical Course ◽  
Venous Drainage ◽  
Review Of The Literature ◽  
Content Type ◽  
Newborn Child ◽  
The Brain ◽  
Fine Print

✓ A case is reported of a newborn child whose predominant lesion was a metastatic choriocarcinoma of the brain. The outstanding features of the clinical course were repeated episodes of intracranial and subgaleal hemorrhage. Angiograms revealed large areas of pooling of contrast medium without neovascularization or rapid venous drainage. A review of the literature demonstrated the infrequency with which this lesion has been encountered.

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