Necrosis as a prognostic criterion in malignant supratentorial, astrocytic gliomas

Nelson, James S.; Tsukada, Yoshiaki; Schoenfeld, David; Fulling, Keith H.; Lamarche, Jacques B.; Peress, Nancy S.

doi:10.1002/1097-0142(19830801)52:3<550::aid-cncr2820520327>3.0.co;2-c

Cited by 255 publications

(65 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…25,26 In contrast, coagulative necrosis represents the majority of cell death in GBMs and its degree is inversely related to patient survival. 2,27,28 The mere presence of focal necrosis remains one of the strongest independent markers of poor prognosis. 7,29,30 Coagulative necrosis is seen Vaso-occlusion, hypoxia, and necrosis in glioblastoma DJ Brat and EG Van Meir pathologically as either microscopic foci with surrounding pseudopalisading cells ('pseudopalisading necrosis') or as large confluent expanses of dying tumor and nontumor elements.…”

Section: Necrogenesis In Gbmmentioning

confidence: 41%

Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis, and accelerated growth in glioblastoma

Brat

Meir

2004

Laboratory Investigation

287

276

View full text Add to dashboard Cite

Glioblastoma (GBM) has explosive biologic properties with rapid clinical progression leading to death. Its distinguishing pathologic features, necrosis with surrounding pseudopalisades and microvascular hyperplasia, are believed to be instrumental to its accelerated growth. Microvascular hyperplasia arises in response to the secretion of proangiogenic factors by hypoxic pseudopalisades and allows for peripheral neoplastic expansion. Mechanisms underlying necrosis and hypoxia remain obscure, but vaso-occlusive and prothrombotic contributions could be substantial. Recent investigations on the origin of pseudopalisades suggest that this morphologic phenomenon is created by a tumor cell population actively migrating away from a central hypoxic region and that, in at least a significant subset, hypoxia-induced migration appears due to vasoocclusion caused by intravascular thrombosis. Both vascular endothelial growth factor induced vascular permeability to plasma coagulation factors and the increased neoplastic expression of tissue factor likely contribute to a prothrombotic state favoring intravascular thrombosis. In addition to prothrombotic mechanisms, vaso-occlusion could also result from angiopoietin-2-mediated endothelial cell apoptosis and vascular regression, which follows neoplastic co-option of native vessels in animal models of gliomas. Vasoocclusive and prothrombotic mechanisms in GBM could readily explain the presence of pseudopalisades and coagulative necrosis in tissue sections, the emergence of central contrast enhancement and its rapid peripheral expansion on neuroimaging, and the dramatic shift to an accelerated rate of clinical progression. Since the hypoxic induction of angiogenesis appears to support further neoplastic growth, therapeutic targeting of the underlying vascular pathology and thrombosis could provide a new means to prolong time to progression.

show abstract

Section: Necrogenesis In Gbmmentioning

confidence: 41%

Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis, and accelerated growth in glioblastoma

Brat

Meir

2004

Laboratory Investigation

287

276

View full text Add to dashboard Cite

show abstract

“…However, the incidence and natural history of hypoxia in human brain tumours before and during radiotherapy is poorly understood. The benefit of the use of hypoxic cell radiosensitizers with radiotherapy for gliomas was has been reported for metronidazole (Urtasun et al, 1976) but not for misonidazole (Bleehen et al, 1981;Nelson D et al, 1983;Green et al, 1984).…”

mentioning

confidence: 98%

“…Malignant gliomas are highly cellular tumours which normally contain necrosis (Nelson J et al, 1983;Wilden et al, 1987) and which are commonly assumed to contain substantial numbers of hypoxic cells. Almost all macroscopic transplanted tumours in rodents contain viable hypoxic cells, which are a major cause of radioresistance (Moulder and Rockwell, 1984;Rockwell and Moulder, 1990).…”

mentioning

confidence: 99%

Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption

Parliament¹,

Franko²,

Allalunis-Turner³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary In contrast to reports of extensive hypoxia in human gliomas in situ measured by P02 histography, non-invasive methods of assessing glioma oxygenation, including nitroimidazole binding, have yielded surprisingly contradictory results. In order to investigate the relationship of necrosis, hypoxia, nitroreductase activity and cellular respiration in human gliomas, subcutaneous models using the human glioma cell lines M059K, M006 and M01 Ob were developed in the murine SCID host. Intracranial growth of the M006 line was achieved in nude rats. The nitroreductive capacity of glioma cell lines was assessed and found to be similar to transplanted tumours previously reported in the literature. This suggests that if substantial numbers of viable hypoxic cells were present in situ in gliomas, then nitroimidazole-binding techniques should be capable of identifying them. Inter-tumour variability in the amount of necrosis was seen. M006 xenografts growing in subcutaneous and intracranial sites revealed extensive necrotic regions histologically, some of which were surrounded by cells labelled heavily for [3H]misonidazole, while other areas were lightly labelled. Similar binding patterns were seen for subcutaneous M059K tumours, while subcutaneous M01 Ob tumours display necroses of which almost all were surrounded by heavily labelled cells. The oxygen consumption rates of tumour cell lines grown in vivo, in which venous P02 concentrations are of the order of 2-5%, were two to sevenfold less than those of the same lines grown as monolayers in vitro under oxygen concentrations of 18%. We postulate that glioma cell lines behave as 'oxygen conformers', in that their rate of oxygen consumption appears to vary with the availability of oxygen. Together with the misonidazole-binding data, the results in this glioma tumour model are consistent with coordinate inhibition or down-regulation of respiration under moderate hypoxia.

show abstract

“…As a result of the studies which have demonstrated the importance of necrosis and pointed to MA patients' comparatively shorter survival times (4, 8,11,25), necrosis has become an important diagnostic criterion in GM for many pathologists. The presence or absence of necrosis is a key criterion in diagnosing the most anaplastic form of GBM (25). However, the proportion of GBM without histopathological necrosis is reported to be 8-34% in the literature (4).…”

Section: Ekici Ma Et Al: Analysis Of the Mortality Probability Of Prmentioning

confidence: 99%

Analysis of the mortality probability of preoperative MRI features in malignant astrocytomas

Ekici¹,

Bulut²,

Tucer³

et al. 2011

Turkish Neurosurgery

View full text Add to dashboard Cite

AIm:The aim of the present study is to analyze the effects of the MRI features on the recurrence time and prognosis, and to emphasize the analyses of mortality risks in malignant astrocytomas. mAterIAl and methOds:The effects of preoperative MRI features on prognosis were studied for follow-up period of 45 months, from November 1999 to August 2003, on a total of 79 patients' 41 cases of total resection and 38 cases of subtotal resection diagnosed to have malignant astrocytoma subsequent to craniotomy. results:The cases of gross total resection had 2.2 times as high survival rate as those in the subtotal resection group (p<0.01). The comparison of the cases in the groups in relation to their ages revealed that mortality rate rose 4.35 times (p<0.01) in the age group of 60 years and above, and 2.1 times in the age group of 45-59 years. When cases without necrosis were compared with the group containing necrosis of grade 1, 2, 3, it was observed that the probability of mortality increased 3.84 (p<0.01), 4.15 times (p<0.01) in the case of necrosis of grade 2 and 3, respectively by means of Cox regression model. BulGulAr: Cox regresyon analizinde; gross total rezeksiyon yapılan olguların subtotal rezeksiyon grubuna göre 2,2 kat hayatta kalma olasılığına sahip olduğu görüldü (p<0,01). Yaş gruplarında ise, 60 ve üzeri yaş grubundaki olguların ölüm olasılığının 4.4 kat arttığı (P<0.01), ölüm olasılığındaki bu artışın 45-59 yaş grubunda 2,1 kat olduğu tespit edildi. Nekroz içermeyen olgular 1, 2 ve 3. derece nekroz içeren grupla karşılaştırıldığında; 2. derece nekroz içeren grupta ölüm olasılığının 3,84 kat arttığı (P<0,01), 3. derece nekroz içeren grupta ise ölüm olasılığının 4,15 kat (p<0,01) arttığı görüldü. sOnuÇ: Malign astrositomalarda Preoperatif MRI'daki nekroz hastalığın prognozu açısından önemli bir klinik belirleyici olarak görünmektedir.

show abstract

Necrosis as a prognostic criterion in malignant supratentorial, astrocytic gliomas

Cited by 255 publications

References 3 publications

Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis, and accelerated growth in glioblastoma

Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis, and accelerated growth in glioblastoma

Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption

Analysis of the mortality probability of preoperative MRI features in malignant astrocytomas

Contact Info

Product

Resources

About