Complete regression of anaplastic astrocytoma by intravenous tumor necrosis factor-alpha (TNFα) after recurrence: A case report

Maruno, Motohiko; Yoshimine, Toshiki; Nakata, Hiroyuki; Nishioka, K.; Kato, Aitaro; Hayakawa, Tõru

doi:10.1016/0090-3019(94)90012-4

Cited by 8 publications

(4 citation statements)

References 16 publications

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“…Since the therapeutic effect of T N F a on malignant gliomas also varies from case to case [11,20], the prediction of efficacy of exogenous TNFc~ in individual cases is of critical importance in selecting candidates for this cytokine therapy. In the present series of tumours, TNF-BS § tumour cells were particularly abundant in 4 out of the 19 cases (21%).…”

Section: Discussionmentioning

confidence: 99%

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Cellular targets of exogenous tumour necrosis factor-alpha (TNF?) in human gliomas

et al. 1996

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To identify the cellular targets of TNF alpha in human gliomas, a total of 30 surgical specimens (12 glioblastomas, 4 anaplastic astrocytomas, 3 astrocytomas, 7 brains adjacent to tumour (BAT), 4 histologically normal-appearing brains) were examined by in vitro binding technique using biotinylated TNF alpha. The TNF-binding sites (TNF-BS) were recognized in the tumour cells in 8 of the 12 glioblastomas, 3 of the 4 anaplastic astrocytomas and in all the 3 astrocytomas. The TNF-BS were also recognized in the vascular endothelial cells in all these cases. The presence of TNF-BS in blood vessels ranged from 7.7 to 74.4% of the background vessels. This wide range of variation in the presence of TNF-BS within the tumour cells and tumour blood vessels may be relevant to the variable response of individual tumours to TNF alpha therapy. Since the tissue of normal brain, which lacks TNF-BS, might hardly be affected by this cytokine, administration of TNF alpha may be considered as an adjuvant therapy in selected groups of patients.

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Section: Discussionmentioning

confidence: 99%

“…Since a certain population of malignant gliomas regress in response to TNFc~, this cytokine has been considered as a candidate for adjuvant treatment of these turnouts [12,20]. The clinical trials, however, revealed that the therapeutic result varies largely from case to case [11,20].…”

Section: Introductionmentioning

confidence: 99%

Cellular targets of exogenous tumour necrosis factor-alpha (TNF?) in human gliomas

et al. 1996

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“…Most phase I studies reported a maximum tolerable dose (MTD) of 200-545 mg=m 2 with protracted infusion for 24 hours [73,74]. However, even escalated dosages produced minimal tumor responses in phase II studies [75,76], with only a few anecdotal reports of tumor regression [77]. At the same time, experiments in mouse models showed that the efficient TNF dose, in terms of tumor response, is approximately 50 mg=kg -extrapolated to humans, a 10-fold higher dose than the MTD [45].…”

Section: Cytostatic Agentsmentioning

confidence: 99%

Isolierte Extremitätenperfusion mit TNFα und Zytostatika: eine Revolution in der Behandlung lokal fortgeschrittener Weichgewebssarkome der Extremitäten

et al. 2009

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Zusammenfassung. Grundlagen: Lokal fortgeschrittene Weichgewebssarkome der Extremitäten stellen mit dem Ziel der lokalen Tumorkontrolle und dem gleichzeitigen Funktionserhalt eine stetige operative Herausforderung dar. Die isolierte hypertherme Extremitätenperfusion mit TNF und Melphalan ist als neoadjuvante Therapieoption eingeführt worden, um Amputationen zu vermeiden, ohne die Prognose zu verschlechtern.Methodik: Literaturrecherche über die PubMed Datenbank mittels Entrez, kombiniert mit den Erfahrungen der Autoren.Ergebnisse: Anhand mehrerer Studien wurde belegt, dass durch die ILP ein Extremitätenerhalt in bis zu 80 % der Fälle bei tolerablen lokalen und systemischen Komplikationen zu realisieren ist. Die Lokalrezidivrate liegt zwischen 10-20 %.Schlussfolgerungen: Die isolierte Extremitätenperfu-sion mit TNF und Melphalan hat die Behandlung von lokal fortgeschrittenen Weichgewebssarkomen der Extremitäten durch eine deutliche Reduktion der Amputationsraten revolutioniert. Weitere Fortschritte können nach Einführung neuer Substanzen erwartet werden.

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“…TNF, for example, suppresses the transcription of TM [25,26], or promotes the degradation and internalization of TM [27]. Thus, the TNF-induced regression of astrocytic tumors [28,29] might be mediated in part by the 159 down-regulation of TM expression. The altered expression of TM in the tumor vessels and tumor cells seems to provide an intriguing insight into the pathophysiology of brain tumors and into the development of novel maneuvers to control tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Expression of thrombomodulin in astrocytomas of various malignancy and in gliotic and normal brains

et al. 1994

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A total of 22 surgical specimens, 16 astrocytomas with various malignancy, 3 brains adjacent to tumor and 3 brains with non-neoplastic lesion, was investigated immunohistochemically for the expression of thrombomodulin (TM). This membrane protein is localized on the vascular endothelium of nearly every human tissue and plays a crucial role in the maintenance of antithrombotic property of the endothelial cells. Although the normal cerebral vessels were negative for TM, the tumor vessels were positive for TM. The increased expression of TM was, however, demonstrated not only in glioblastomas but also in low-grade astrocytomas. Furthermore, the vessels in the brains adjacent to tumor and gliotic brains were also positive for TM. Those observations suggested that the tendency of intratumoral bleeding, which is rather characteristic of glioblastomas, is not simply explained by the altered expression of vascular endothelial TM. In two cases of glioblastoma, not only the blood vessels but also the tumor cells were positive. Considering the mitogenic activity of thrombin, a ligand for TM, the increased expression of TM might be related to the tumor neovascularization and also the tumor growth.

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Complete regression of anaplastic astrocytoma by intravenous tumor necrosis factor-alpha (TNFα) after recurrence: A case report

Cited by 8 publications

References 16 publications

Cellular targets of exogenous tumour necrosis factor-alpha (TNF?) in human gliomas

Cellular targets of exogenous tumour necrosis factor-alpha (TNF?) in human gliomas

Isolierte Extremitätenperfusion mit TNFα und Zytostatika: eine Revolution in der Behandlung lokal fortgeschrittener Weichgewebssarkome der Extremitäten

Expression of thrombomodulin in astrocytomas of various malignancy and in gliotic and normal brains

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