Chemotherapy of brain tumors

1972 ◽  
Vol 37 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Charles H. Tator
Keyword(s):  
Brain Tumors ◽  
Chemotherapeutic Agent ◽  
Normal Brain ◽  
Neoplastic Cells ◽  
Central Mass ◽  
Content Type ◽  
Intracerebral Tumor ◽  
Almost All ◽  
The Brain ◽  
Adjacent Brain

✓ The uptake and distribution in brain tumors of a parenterally administered chemotherapeutic agent were studied in mice bearing intracerebral implants of a transplantable ependymoblastoma. Tritiated methotrexate (3H-MTX) was injected intravenously, and autoradiographs of the tumors and adjacent brain were prepared at 2, 10, and 60 min after injection using a technique suitable for soluble compounds. In the tumors at 2 min the drug was mainly intravascular and interstitial while at 60 min the drug was mainly intracellular. This is the first demonstration of cellular uptake of a chemotherapeutic agent by neoplastic cells within the brain. At 60 min, almost all the cells in the central mass of the intracerebral tumors were heavily labeled. However, cells at the periphery of the mass and those infiltrating into adjacent brain showed scanty labeling. Uptake in normal brain was very low, while uptake in edematous brain adjacent to the tumors was much higher although not as high as in the tumors. The study shows that this chemotherapeutic agent is capable of penetrating into the neoplastic cells of an intracerebral tumor following parenteral administration, but that the degree of penetration varies considerably depending on the location of the cells within the brain.

scholarly journals LPTO-06. A NOVEL BRAIN-PERMEANT CHEMOTHERAPEUTIC AGENT FOR THE TREATMENT OF BREAST CANCER LEPTOMENINGEAL METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i7-i7
Author(s):  
Jiaojiao Deng ◽  
Sophia Chernikova ◽  
Wolf-Nicolas Fischer ◽  
Kerry Koller ◽  
Bernd Jandeleit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Tumors ◽  
Cell Lines ◽  
Chemotherapeutic Agent ◽  
Leptomeningeal Metastasis ◽  
Breast Cancer Cell Lines ◽  
Normal Brain ◽  
Breast Cancers

Abstract Leptomeningeal metastasis (LM), a spread of cancer to the cerebrospinal fluid and meninges, is universally and rapidly fatal due to poor detection and no effective treatment. Breast cancers account for a majority of LMs from solid tumors, with triple-negative breast cancers (TNBCs) having the highest propensity to metastasize to LM. The treatment of LM is challenged by poor drug penetration into CNS and high neurotoxicity. Therefore, there is an urgent need for new modalities and targeted therapies able to overcome the limitations of current treatment options. Quadriga has discovered a novel, brain-permeant chemotherapeutic agent that is currently in development as a potential treatment for glioblastoma (GBM). The compound is active in suppressing the growth of GBM tumor cell lines implanted into the brain. Radiolabel distribution studies have shown significant tumor accumulation in intracranial brain tumors while sparing the adjacent normal brain tissue. Recently, we have demonstrated dose-dependent in vitro and in vivo anti-tumor activity with various breast cancer cell lines including the human TNBC cell line MDA-MB-231. To evaluate the in vivo antitumor activity of the compound on LM, we used the mouse model of LM based on the internal carotid injection of luciferase-expressing MDA-MB-231-BR3 cells. Once the bioluminescence signal intensity from the metastatic spread reached (0.2 - 0.5) x 106 photons/sec, mice were dosed i.p. twice a week with either 4 or 8 mg/kg for nine weeks. Tumor growth was monitored by bioluminescence. The compound was well tolerated and caused a significant delay in metastatic growth resulting in significant extension of survival. Tumors regressed completely in ~ 28 % of treated animals. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, Quadriga’s new agent could be effective as a therapeutic for both primary and metastatic brain tumors such as LM. REF: https://onlinelibrary.wiley.com/doi/full/10.1002/pro6.43

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.

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.

Quantification and pharmacokinetics of blood-brain barrier disruption in humans

1996 ◽  
Vol 85 (6) ◽  
pp. 1056-1065 ◽  
Author(s):  
Bernhard Zünkeler ◽  
Richard E. Carson ◽  
Jeff Olson ◽  
Ronald G. Blasberg ◽  
Hetty Devroom ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Normal Brain ◽  
Content Type ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption ◽  
Fine Print

✓ Hyperosmolar blood-brain barrier disruption (HBBBD), produced by infusion of mannitol into the cerebral arteries, has been used in the treatment of brain tumors to increase drug delivery to tumor and adjacent brain. However, the efficacy of HBBBD in brain tumor therapy has been controversial. The goal of this study was to measure changes in vascular permeability after HBBBD in patients with malignant brain tumors. The permeability (K1) of tumor and normal brain blood vessels was measured using rubidium-82 and positron emission tomography before and repeatedly at 8- to 15-minute intervals after HBBBD. Eighteen studies were performed in 13 patients, eight with glioblastoma multiforme and five with anaplastic astrocytoma. The HBBBD increased K1 in all patients. Baseline K1 values were 2.1 ± 1.4 and 34.1 ± 22.1 µl/minute/ml (± standard deviation) for brain and tumor, respectively. The peak absolute increases in K1 following HBBBD were 20.8 ± 11.7 and 19.7 ± 10.7 µl/minute/ml for brain and tumor, corresponding to percentage increases of approximately 1000% in brain and approximately 60% in tumor. The halftimes for return of K1 to near baseline for brain and tumor were 8.1 ± 3.8 and 4.2 ± 1.2 minutes, respectively. Simulations of the effects of HBBBD made using a very simple model with intraarterial methotrexate, which is exemplary of drugs with low permeability, indicate that 1) total exposure of the brain and tumor to methotrexate, as measured by the methotrexate concentration-time integral (or area under the curve), would increase with decreasing infusion duration and would be enhanced by 130% to 200% and by 7% to 16%, respectively, compared to intraarterial infusion of methotrexate alone; and 2) exposure time at concentrations above 1 µM, the minimal concentration required for the effects of methotrexate, would not be enhanced in tumor and would be enhanced by only 10% in brain. Hyperosmolar blood-brain barrier disruption transiently increases delivery of water-soluble compounds to normal brain and brain tumors. Most of the enhancement of exposure results from trapping the drug within the blood-brain barrier, an effect of the very transient alteration of the blood-brain barrier by HBBBD. Delivery is most effective when a drug is administered within 5 to 10 minutes after disruption. However, the increased exposure and exposure time that occur with methotrexate, the permeability of which is among the lowest of the agents currently used clinically, are limited and the disproportionate increase in brain exposure, compared to tumor exposure, may alter the therapeutic index of many drugs.

Brain Tumor Reporting and Data System: A Pictorial Review

Neurographics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 175-185
Author(s):  
B. Rao ◽  
I. Ikuta ◽  
A. Mahajan ◽  
A.A. Karam ◽  
V.M. Zohrabian
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Response To Therapy ◽  
Data System ◽  
Imaging Features ◽  
New Paradigm ◽  
Advantages And Disadvantages ◽  
Pictorial Review ◽  
Almost All ◽  
The Brain

Brain tumors are a diverse group of neoplasms that are a source of substantial morbidity and mortality worldwide. Primary gliomas constitute almost all malignant brain tumors, with the most aggressive as well as most common form in adults, grade IV glioma or glioblastoma multiforme, carrying an especially poor prognosis. Neuroimaging is critical not only in the identification of CNS tumor but also in treatment-planning and assessing the response to therapy. Structured reporting continues to gain traction in radiology by reducing report ambiguity and improving consistency, while keeping referring clinicians and patients informed. The Brain Tumor Reporting and Data System (BT-RADS) is a relatively new paradigm that attempts to simplify and maximize consistency in radiologic reporting. BT-RADS incorporates MR imaging features, clinical assessment, and timing of therapy to assign each study a score or category, which is, in turn, linked to a management suggestion. The purpose of this pictorial review article is to familiarize radiologists and nonradiology neurologic specialists alike with BT-RADS, highlighting both advantages and limitations, in the hope that adoption of this system might ultimately facilitate more effective communication and improve consistency among reports.Learning Objective: To describe the features and underscore the advantages and disadvantages of the Brain Tumor Reporting and Data System (BT-RADS), a relatively new classification system that attempts to simplify and maximize consistency in radiologic reporting

Regional blood flow in RT-9 brain tumors

1983 ◽  
Vol 58 (6) ◽  
pp. 863-873 ◽  
Author(s):  
Ronald G. Blasberg ◽  
Peter Molnar ◽  
Marc Horowitz ◽  
Paul Kornblith ◽  
Roger Pleasants ◽  
...  
Keyword(s):  
Blood Flow ◽  
Brain Tumors ◽  
Tumor Size ◽  
Regional Blood Flow ◽  
Tumor Implantation ◽  
Content Type ◽  
Carbon 14 ◽  
Tumor Periphery ◽  
The Brain ◽  
Anatomic Region

✓ Regional blood flow (BF) was measured in RT-9 experimental brain tumors using carbon-14 labeled iodoantipyrine, the Kety tissue-exchange equations, and quantitative autoradiographic techniques. Blood flow was variable within tumor tissue, and the range of BF increased with increasing tumor size; the overall range was 6 to 138 ml/100 gm/min and the maximum range within an individual tumor was 55 ml/100 gm/min. In all but one case, mean tumor BF was less than that in the same anatomic region of the contralateral hemisphere (CBA). The magnitude of BF within individual tumor foci generally could be related to tumor size, location (intraparenchymal versus extraparenchymal), and the presence of necrosis or cysts; it was lower in the geometric centers than in the periphery of medium-sized and large tumors. Brain adjacent to tumor had higher BF's than the tumor periphery; generally, the BF in the brain adjacent to the tumor was less than that in the CBA. A global depression of BF was observed within tumor-free cortex and corpus callosum of the hemisphere ipsilateral to tumor implantation and primary growth, suggesting a hemispheric reduction in metabolic and functional activity.

Primary diffuse leptomeningeal oligodendroglioma

1995 ◽  
Vol 83 (4) ◽  
pp. 724-728 ◽  
Author(s):  
Robert Chen ◽  
David R. Macdonald ◽  
David A. Ramsay
Keyword(s):  
High Dose Chemotherapy ◽  
Postmortem Examination ◽  
High Dose ◽  
Imaging Studies ◽  
Neoplastic Cells ◽  
Content Type ◽  
Suprasellar Cistern ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Fine Print

✓ The authors describe a case of a diffuse primary leptomeningeal oligodendroglioma in a 17-year-old girl who presented with raised intracranial pressure and hydrocephalus. She underwent imaging studies and a left frontotemporal craniotomy that revealed a cystic oligodendroglioma in the suprasellar cistern and spread of neoplastic cells to the spinal leptomeninges. The tumor showed little response to maximum radiotherapy and chemotherapy, and the patient died from complications of high-dose chemotherapy 2 years after diagnosis. Postmortem examination of the brain and spinal cord revealed diffuse meningeal infiltration by neoplastic cells and no evidence of an intraparenchymal origin. Glial heterotopias were noted at several sites along the brain base, adding circumstantial support to the theory that leptomeningeal gliomas are derived from ectopic glial tissue in the subarachnoid space.

Localized 31P magnetic resonance spectroscopy of large pediatric brain tumors

1990 ◽  
Vol 72 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Leslie N. Sutton ◽  
Robert E. Lenkinski ◽  
Bruce H. Cohen ◽  
Roger J. Packer ◽  
Robert A. Zimmerman
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Brain Tumors ◽  
Malignant Tumors ◽  
Benign Tumors ◽  
Resonance Spectroscopy ◽  
Normal Brain ◽  
Content Type ◽  
Metabolic Fingerprint

✓ Fourteen children aged 1 week to 16 years, with a variety of large or superficial brain tumors, underwent localized in vivo 31P magnetic resonance spectroscopy of their tumor. Quantitative spectral analysis was performed by measuring the area under individual peaks using a computer algorithm. In eight patients with histologically benign tumors the spectra were considered to be qualitatively indistinguishable from normal brain. The phosphocreatine/inorganic phosphate ratio (PCr/Pi) averaged 2.0. Five patients had histologically malignant tumors; qualitatively, four of these were considered to have abnormal spectra, showing a decrease in the PCr peak. The PCr/Pi ratio for this group averaged 0.85, which was significantly lower than that seen in the benign tumor group (p < 0.05). No difference between the two groups was seen in adenosine triphosphate or phosphomonoesters. It is concluded that a specific metabolic “fingerprint” for childhood brain tumors may not exist, but that some malignant tumors show a pattern suggestive of ischemia.

Automated brain tumor segmentation from multimodal MRI data based on Tamura texture feature and an ensemble SVM classifier

2019 ◽  
Vol 12 (4) ◽  
pp. 466-480
Author(s):  
Li Na ◽  
Xiong Zhiyong ◽  
Deng Tianqi ◽  
Ren Kai
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Superior Performance ◽  
Support Vector ◽  
Svm Classifier ◽  
Data Set ◽  
Original Solution ◽  
Content Type ◽  
Tumor Region ◽  
The Brain

Purpose The precise segmentation of brain tumors is the most important and crucial step in their diagnosis and treatment. Due to the presence of noise, uneven gray levels, blurred boundaries and edema around the brain tumor region, the brain tumor image has indistinct features in the tumor region, which pose a problem for diagnostics. The paper aims to discuss these issues. Design/methodology/approach In this paper, the authors propose an original solution for segmentation using Tamura Texture and ensemble Support Vector Machine (SVM) structure. In the proposed technique, 124 features of each voxel are extracted, including Tamura texture features and grayscale features. Then, these features are ranked using the SVM-Recursive Feature Elimination method, which is also adopted to optimize the parameters of the Radial Basis Function kernel of SVMs. Finally, the bagging random sampling method is utilized to construct the ensemble SVM classifier based on a weighted voting mechanism to classify the types of voxel. Findings The experiments are conducted over a sample data set to be called BraTS2015. The experiments demonstrate that Tamura texture is very useful in the segmentation of brain tumors, especially the feature of line-likeness. The superior performance of the proposed ensemble SVM classifier is demonstrated by comparison with single SVM classifiers as well as other methods. Originality/value The authors propose an original solution for segmentation using Tamura Texture and ensemble SVM structure.

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.

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