Phase II Trial of Murine 131I-Labeled Antitenascin Monoclonal Antibody 81C6 Administered Into Surgically Created Resection Cavities of Patients With Newly Diagnosed Malignant Gliomas

Reardon, David A.; Akabani, Gamal; Coleman, R. Edward; Friedman, Allan H.; Friedman, Henry S.; Herndon, James E.; Cokgor, Ilkcan; McLendon, Roger E.; Pegram, Charles N.; Provenzale, James M.; Quinn, Jennifer A.; Rich, Jeremy; Regalado, Lorna V.; Sampson, John H.; Shafman, Timothy D.; Wikstrand, Carol J.; Wong, Terence Z.; Zhao, Xiao Guang; Zalutsky, Michael R.; Bigner, Darell D.

doi:10.1200/jco.20.5.1389

Cited by 183 publications

(87 citation statements)

References 29 publications

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“…8 -14 Because the clinical outcome of patients with GBM still is very poor, several groups started treating patients with GBM using radiolabeled monoclonal anti-TN-C antibodies, which were placed into the postoperative cavity using an indwelling (Rickam or Omaya) catheter. [15][16][17][18][19][20][21][22][23][24] Riva et al 15 reported that the average overall survival of 9 -10 months in patients with GBM could be prolonged to 19 -25 months using radioimmunotherapy. No systematic data exist in the literature about the frequency and cellular localization or the relation of TN-C to overall survival in patients with other brain tumors, such as low-grade astrocytomas, meningiomas, and schwannomas.…”

Section: Resultsmentioning

confidence: 99%

Expression of tenascin‐C in various human brain tumors and its relevance for survival in patients with astrocytoma

Leins

Riva

Lindstedt

et al. 2003

Cancer

133

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BACKGROUNDTenascin‐C (TN‐C), a large extracellular matrix (ECM) glycoprotein with a molecular weight of 180–250 kilodaltons, is present in several normal adult tissues. TN‐C is up‐regulated during embryogenesis, in wound healing, and in tumor tissues. Glioblastoma multiforme (GBM) is the most frequent and malignant astrocytic tumor comprised of poorly differentiated, neoplastic astrocytes. Recently, TN‐C‐based radioimmunotherapy was administered to patients with GBM.METHODSIn the current study, the authors used immunohistochemistry to conduct a systematic investigation of TN‐C distribution patterns in normal human brain tissue and in a large variety of brain tumors (n = 485 tumors). Immunoreactivity for TN‐C was assessed with regard to its localization within tumor cells, blood vessels, and ECM using three different monoclonal antibodies (clones BC2, BC4, and TN2).RESULTSIn control human brains, a significant difference was noted in the expression of TN‐C when comparing gray with white matter using either Western blot analysis or immunohistochemistry. TN‐C was found in the white matter of the frontal, temporal, parietal, and occipital lobes and in the hippocampus, where the immunoreaction was especially strong in the hippocampal formation. In 181 astrocytomas of different grades (World Health Organization [WHO] Grade 2–4), TN‐C immunopositivity was seen to varying degrees in the cellular and stromal components of the tumor and in tumor‐associated vessels. Glioblastomas (n = 113 tumors) showed strong immunopositivity in the vessels and moderate immunopositivity of the ECM. A statistically significant reduction of TN‐C immunopositivity in tumor‐associated vessels or ECM was observed in anaplastic astrocytomas (WHO Grade 3) compared with GBM (WHO Grade 4). A Kaplan–Meier analysis showed that patients who had GBM lesions that lacked TN‐C immunopositivity in the ECM had a significantly longer survival (median, 28 months; standard error, 7.8 months) (n = 12 patients) compared with patients who had GBM lesions with TN‐C immunopositivity (median, 12 months; standard error, 1.6 months) (n = 87 patients). In meningiomas (n = 24 tumors), the neoplastic cells, the ECM of the tumor, and the vessels were TN‐C negative. In schwannomas (n = 31 tumors), the tumor cells were TN‐C negative; whereas, in > 50% of tumors, the vessels and the ECM of regressively altered tumor areas were positive. In metastatic carcinomas (n = 53 tumors), the tumor cells were negative; seldom were vessels stained positive for TN‐C. Focal areas of the ECM, often accompanied with fibrotic changes, were immunopositive for TN‐C.CONCLUSIONSThe most constant TN‐C immunopositivity was noted in the ECM of the fibrotic stroma in highly malignant brain tumors and along the tumor border, especially in high‐grade astrocytomas. The current results suggest that TN‐C expression may be correlated with the grade of malignancy in astrocytic tumors and that the presence or absence of TN‐C expression in the stroma of astrocytic tumors may play a not yet clearly understood role in shortening or prolonging, respectively, the survival of patients. Cancer 2003. © 2003 American Cancer Society.

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Section: Resultsmentioning

confidence: 99%

Expression of tenascin‐C in various human brain tumors and its relevance for survival in patients with astrocytoma

Leins

Riva

Lindstedt

et al. 2003

Cancer

133

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“…Nevertheless, these markers should not be disregarded. Tenascin is a glycoprotein responsible for producing gliogenic precursors and has been a target for radioimmunotherapy in brain tumors (65,158). The tenascin c (TNC) gene on chromosome 9 seems upregulated in infant ependymomas (76), and its protein expression seems relatively high in pediatric cases (35), whereas the presence of intercellular tenascin has been identified as an adverse prognostic marker in an albeit small immunohistochemical study of pediatric ependymomas (129).…”

Section: Immunohistochemical and Genomic Markersmentioning

confidence: 99%

“…Differences in fluorescent intensities between the two markers along the length of each chromosome subsequently identify regions of genetic gain and loss within the tumor genome. A review of literature on CGH analyses of ependymoma since the year 2000 revealed 13 studies, collectively evaluating 303 primary tumors with genomic abnormalities (58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70). We have undertaken a comparative meta-analysis of this cohort.…”

Section: Molecular Distinctions Between Pediatric and Adult Ependymomasmentioning

confidence: 99%

Pediatric Ependymoma: Biological Perspectives

Kilday

Rahman

Dyer

et al. 2009

Molecular Cancer Research

167

204

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Pediatric ependymomas are enigmatic tumors that continue to present a clinical management challenge despite advances in neurosurgery, neuroimaging techniques, and radiation therapy. Difficulty in predicting tumor behavior from clinical and histological factors has shifted the focus to the molecular and cellular biology of ependymoma in order to identify new correlates of disease outcome and novel therapeutic targets. This article reviews our current understanding of pediatric ependymoma biology and includes a meta-analysis of all comparative genomic hybridization (CGH) studies done on primary ependymomas to date, examining more than 300 tumors. From this meta-analysis and a review of the literature, we show that ependymomas in children exhibit a different genomic profile to those in adults and reinforce the evidence that ependymomas from different locations within the central nervous system (CNS) are distinguishable at a genomic level. Potential biological markers of prognosis in pediatric ependymoma are assessed and the ependymoma cancer stem cell hypothesis is highlighted with respect to tumor resistance and recurrence. We also discuss the shifting paradigm for treatment modalities in ependymoma that target molecular alterations in tumor-initiating cell populations. (Mol Cancer Res 2009;7(6):765-86)

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“…These ECM components are highly abundant in tumours and are often more stable than antigens located on the cell surface of tumour cells. Radio labelled antibodies specific to TNC (Tenascin-C domain C) domains A1 and D have been used successfully in the clinic to treat glioma and lymphoma [34]. The EDB-targeting antibody L19 has been used as a vehicle for TNFα (Alpha) and has been shown to induce necrosis in tumours.…”

Section: Influence Of Tumour-associated Fibroblasts On Tumour Behaviourmentioning

confidence: 99%

Microenvironment–A Role in Tumour Progression and Prognosis

Muppalla

Muddana²,

Dorankula³

et al. 2013

JCDR

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Phase II Trial of Murine 131I-Labeled Antitenascin Monoclonal Antibody 81C6 Administered Into Surgically Created Resection Cavities of Patients With Newly Diagnosed Malignant Gliomas

Cited by 183 publications

References 29 publications

Expression of tenascin‐C in various human brain tumors and its relevance for survival in patients with astrocytoma

Expression of tenascin‐C in various human brain tumors and its relevance for survival in patients with astrocytoma

Pediatric Ependymoma: Biological Perspectives

Microenvironment–A Role in Tumour Progression and Prognosis

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