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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microvascular proliferation, a hallmark of malignant brain tumors, represents an attractive target of anticancer research, especially because of the quiescent nonproliferative endothelium of the normal brain. Cerebral neoplasms sequester copper, a trace metal that modulates angiogenesis. Using a rabbit brain tumor model, normocupremic animals developed large vascularized VX2 carcinomas. By contrast, small, circumscribed, relatively avascular tumors were found in the brains of rabbits copper-depleted by diet and penicillamine treatment (CDPT). The CDPT rabbits showed a significant decrease in serum copper, copper staining of tumor cell nuclei, microvascular density, the tumor volume, endothelial cell turnover, and an increase in the vascular permeability (breakdown of the blood-brain barrier), as well as peritumoral brain edema. In non-tumor-bearing animals, CDPT did not alter the vascular permeability or the brain water content. CDPT also inhibited the intracerebral growth of the 9L gliosarcoma in F-344 rats, with a similar increase of the peritumoral vascular permeability and the brain water content. CDPT failed to inhibit tumor growth and the vascularization of the VX2 carcinoma in the thigh muscle or the metastases to the lung, findings that may reflect regional differences in the responsiveness of the endothelium, the distribution of copper, or the activity of cuproenzymes. Metabolic and pharmacologic withdrawal of copper suppresses intracerebral tumor angiogenesis; angiosuppression is a novel biologic response modifier for the in situ control of tumor growth in the brain.
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PMID:Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnover by penicillamine and the depletion of copper, an angiogenic cofactor. 170 Jun 17

An in vivo model for correlative imaging studies of intracerebral glial tumors and peritumor brain edema has been developed. Adult male and female cats implanted with 1 x 10(6) or 5 x 10(5) 9L glioma cells had parietal tumors of 4 mm or greater in diameter and showed signs of increased intracranial pressure 13.7 +/- 1.9 days or 19.2 +/- 1.3 days after implantation. No immunosuppression was required and the success rate for tumor growth after implantation was 88%. Histologically, the tumor resembles a malignant astrocytoma. The tumor contained the highest water content (85.94%); peritumor white matter was more edematous (73.01%) than white matter in the contralateral hemisphere (69.04%), sham-operated (69.41%) and control brain (68.76%). There was no correlation between the size of the tumor and water content in tumor or white matter. Increased tissue albumin in peritumor white matter indicated blood-brain barrier dysfunction within the tumor and confirmed the vasogenic origin of the edema. Proton magnetic resonance imaging provided good spatial and contrast resolution with increased signal intensity in edematous white matter, decreasing with distance from the tumor. The large brain of this animal model allows the use of serial imaging and regional correlative biochemical measurements in a single animal. Other advantages of this model are its predictability and the short time required to produce tumors with marked peritumor edema.
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PMID:A feline model for experimental studies of peritumor brain edema. 322 Dec 63

Cerebral edema and fluid-filled cysts are common accompaniments of brain tumors. They contribute to the mass effect imposed by the primary tumor and are often responsible for a patient's signs and symptoms. Cerebral edema significantly increases the morbidity associated with tumor biopsy, excision, radiation therapy, and chemotherapy. Both edema and cyst formation are thought to result from a deficiency in the blood-brain barrier, with consequent extravasation of water, electrolytes, and plasma proteins from altered tumor microvessels. The resultant expansion of the cerebral interstitial space contributes to the elevated intracranial pressure observed with brain tumors. Departure from the typical blood-brain barrier microvascular architecture may only partially explain the occurrence of edema and tumor cyst formation. Biochemical mediators have also been implicated in vascular extravasation. Vascular permeability factor or vascular endothelial growth factor (VPF/VEGF) is a protein that has recently been isolated from a variety of tumors including human brain tumors. VPFb is an extraordinarily potent inducer of both microvascular extravasation (edemagenesis) and the formation of new blood vessels (angiogenesis). Its role in tumor growth and progression would therefore appear pivotal. Herein, the author presents an updated account of the investigation of VPF. Historical and clinical perspectives of the study and treatment of tumor associated edema are provided. The efficacy of high-dose dexamethasone in the treatment of neoplastic brain edema is discussed. A hypothetical role for VPF in edemagenesis is presented and discussed. It is hoped that an expanded understanding of the mechanisms responsible for the genesis of edema will ultimately facilitate therapeutic intervention.
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PMID:The genesis of peritumoral vasogenic brain edema and tumor cysts: a hypothetical role for tumor-derived vascular permeability factor. 751 4

Two aspects of cytokine therapy of intracerebral tumors are considered in this study: modulation of tumor growth in vivo and central nervous system toxicity. Coimplantation of RG-2 glioma cells and retroviral vector producer cell lines was performed to provide a local source of interleukin-2 (IL-2) or IFN-gamma within the tumor and coinitiate an antitumor immune response. We demonstrated that local intratumoral production of IL-2 and IFN-gamma generates a cell-mediated antitumor response in vivo. This response was manifest as a diffuse infiltration of monocytes/macrophages, CD4+ and CD8+ T cells, and activation of microglial OX42+ cells in intracerebral RG2 tumors. The cell-mediated antitumor immune response resulted in the early suppression of intracranial and subcutaneous tumor growth, but the effect was not sustained and there were no tumor regressions. The absence of increased survival of animals with intracranial tumors is explained in part by the severe central nervous system toxicity caused by local production of IL-2 and IFN-gamma. Central nervous system toxicity induced blood-brain barrier disruption, vasogenic brain edema, and dislocation of the brain midline structures, as observed by dynamic magnetic resonance imaging and direct measurements of tissue water content. The clinical application of IL-2 and IFN-gamma gene transfer therapy for intracerebral tumors must consider the potential for severe vasogenic brain edema associated with intracerebral production of these cytokines.
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PMID:RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-gamma. 772 57

To determine if topical dexamethasone administered to brain tumor beds would not only control peritumoral edema and suppress tumor growth but also prevent systemic steroid complications, we studied experimental brain tumors produced in 102 rabbits by implanted VX2 carcinoma cells. We separated 58 animals into three groups: 1) untreated rabbits (n = 15), 2) systemic dexamethasone-treated (4 mg/kg/day) rabbits (n = 18), and 3) topical dexamethasone-treated (2.5 microliters/h, osmotic pump) rabbits (n = 25). We administered systemic or topical dexamethasone from the third day or from the seventh day after tumor implantation, and sacrificed the animals on the 13th day. We compared survival in these three groups with that of another 44 rabbits, beginning treatment on the seventh day. We measured brain water content in the white matter of the sacrificed rabbits by the specific gravity method. We measured the length and width of the brain tumors of all the rabbits and estimated tumor volume. Systemic and topical dexamethasone administered from the third day produced statistically significant inhibition of tumor volume as well as a mean reduction in peritumoral brain edema in most tested sites. Systemic and topical dexamethasone treatment resulted in a statistically significant increase in survival relative to the untreated group. These results suggest that topical dexamethasone is efficacious in a brain tumor model and its administration to brain tumor beds constitutes a new therapeutic modality.
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PMID:The effects of topical dexamethasone on experimental brain tumors and peritumoral brain edema. 797 1

Toxic oxidants (oxygen free radicals) have been implicated in the formation of brain edema from ischemia-reperfusion injury or tumor growth. We investigated the ability of an iron chelator, a calcium channel blocker, and a xanthine oxidase inhibitor to reduce formation of brain edema following a cold lesion in cats. The agents were given independently of each other in an attempt to inhibit the Haber-Weiss reaction, prevent Ca++ modulated uncoupling of oxidative phosphorylation, and inhibit the generation of toxic oxidants via xanthine oxidase, respectively. Pentastarch-deferoxamine conjugate at a dose of 50 mg/kg was given 15 minutes before and 60 minutes after the cold lesion. Nimodipine was given at a dose of 1 mg/kg 1 hour before and 2 hours after the cold lesion. Allopurinol was given at a dose of 50 mg/kg 24 hours before, at the time of the lesion and, 24 and 48 hours after the lesion. Gravimetric measurements of multiple brain areas were performed at 24 hours post-lesion in the pentastarch-deferoxamine and nimodipine groups and at 72 hours post-lesion in the allopurinol group. None of these agents led to significant reduction in brain edema formation as measured with a gravimetric column of kerosene and bromobenzene. Pentastarch-deferoxamine conjugate was utilized to avoid the confounding effects of arterial hypotension which is seen with intravenous deferoxamine. There was even a suggestion of increased edema in the periventricular white matter in animals treated with nimodipine. Taken together, independent inhibition of the Haber-Weiss reaction, of calcium channels, or of xanthine oxidase does not reduce formation of brain edema in the cold lesion model.
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PMID:Proposed toxic oxidant inhibitors fail to reduce brain edema. 797 65

To determine if dexamethasone administered by osmotic pump directly to brain tumors would control peritumoral edema and at the same time suppress tumor growth and prolong survival, the authors studied experimental brain tumors produced in 102 rabbits by implanting VX2 carcinoma cells. Of these, 58 animals were separated into three treatment groups: Group 1 included 15 untreated rabbits; Group 2 included 18 rabbits treated with systemic dexamethasone (4 mg/kg/day); and Group 3 included 25 rabbits treated with local dexamethasone (0.24 mg/day) delivered by osmotic pump. Systemic or local dexamethasone was administered from Day 3 or Day 7 after tumor implantation, and animals were sacrificed on Day 13. A survival study was performed with 44 rabbits separated into the same treatment groups, beginning drug delivery on Day 7. Brain water content in the white matter of sacrificed animals was measured by the specific gravity method. The length and width of the brain tumors in all animals were measured and the tumor volume estimated. Findings showed that systemic and local dexamethasone administered from Day 3 or Day 7 was associated with a significant (5% level) inhibition of tumor volume as well as a mean reduction of brain edema in most tested sites. Systemic and local dexamethasone therapy also resulted in a significant (5% level) increase in survival time relative to the untreated group. These short-term results suggest that locally delivered dexamethasone may constitute a clinically important therapeutic modality.
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PMID:Therapeutic effects of local delivery of dexamethasone on experimental brain tumors and peritumoral brain edema. 841 Feb 50

The aim of the study was to characterize the interendothelial junctions in tumor microvessels of five cases of human glioblastoma multiforme. In addition to morphological analysis, tumors were screened for the expression of junctional proteins, such as occludin, claudin-1, ZO-1 and catenins. The expression of the tight junction protein claudin-1 was lost in the majority of tumor microvessels, whereas claudin-5 and occludin were significantly down-regulated only in hyperplastic vessels. As shown by freeze-fracture analysis, under the conditions of tumor growth tight junction particles of endothelial cells were almost exclusively associated with the exocytoplasmic fracture face, providing evidence for a switch of the particles from the protoplasmic to the external leaflet of the endothelial membrane. These results suggest a relationship between claudin-1 suppression and the alteration of tight junction morphology, which is likely to correlate with the increase of endothelial permeability. Underlining the undifferentiated state of tumor microvessels, plakoglobin, a crucial protein for mature endothelial junctions, was not detectable in most microvessels, whereas beta-catenin was abundantly labeled. In this context, it is of particular interest that the majority of microvascular pericytes were negative for alpha-smooth muscle actin, which is a marker of differentiated pericytes, although pericytes were frequently found in electron micrographs. In conclusion, the data suggest that the increase in microvascular permeability in human gliomas, contributing to the clinically severe symptoms of brain edema, is a result of a dysregulation of junctional proteins.
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PMID:Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. 1096 3

The potential antitumor effect of MX2, a new lipophilic morpholino anthracycline, was compared with those of ACNU or doxorubicin (DOX) using two different rodent glioma models. A mouse subcutaneous glioma model (203 glioma) was used to measure the effect of each drug on reducing the glioma size and a rat 9L intracerebral glioma model (9L glioma) was used to assess the antitumor effect on survival rate in a clinically similar fashion. Treatment with ACNU inhibited tumor growth by 94.6% (p < 0.0001) and complete regression of the tumor was observed in 3 of 25 (12.0%) of the ACNU-treated cases. Tumor growth was inhibited by 32.4% with DOX despite a tendency (p < 0.16) and by 59.4% with MX-2 (p < 0.001); neither of these drugs resulted in complete tumor regression. In the intracerebral glioma rats, only ACNU tended to ameliorate survival rate, but there was no statistical significance. These results suggest that ACNU has the most potent effect but MX2 can be an option for chemotherapy of malignant gliomas. Interestingly, all three drugs significantly elevated the brain water content on both the ipsilateral and contralateral sides of the tumor, although they did not induce brain edema in the normal rat brains. Careful management of brain edema might be required regardless of the drug used during chemotherapy to maximize the prognosis of glioma patients.
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PMID:Antitumor effect and peritumoral brain edema formation in relation to MX2, ACNU, and doxorubicin therapy: a comparative analysis using rodent models of gliomas. 1114 45

Tumor seeding along the biopsy tract is a rare complication in stereotactic biopsy. We present the unique case of a 42-year-old male with epidural tumor seeding along the needle tract after computer tomography-guided stereotactic biopsy of a glioblastoma in the right basal ganglia. Three months after the biopsy and one week following fractionated radiation therapy, the patient died of brain edema and cardiac dilatation. Besides further tumor growth at the primary site, autopsy revealed a right frontal epidural, nodular metastatic tumor at the site of dura incision of the stereotactic biopsy. Histological examination showed a glioblastoma that spread epidurally along the needle tract. This is the first report of an epidural intracranial implantation metastasis of a glioblastoma after stereotactic biopsy.
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PMID:Epidural metastasis of a glioblastoma after stereotactic biopsy: case report. 1169 89


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