Survival in Malignant Peripheral Nerve Sheath Tumours: A Comparison between Sporadic and Neurofibromatosis Type 1-Associated Tumours

Porter, Daniel; Prasad, Vishal; Foster, L. Bryant; Dall, G; Birch, Rolfe; Grimer, R. J.

doi:10.1155/2009/756395

Cited by 125 publications

(135 citation statements)

References 23 publications

(31 reference statements)

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“…Current treatment options are restricted to complete surgical resection with clear margins; however, the local recurrence of MPNSTs is high (from 32% to 65%; ref. 9).…”

Section: Introductionmentioning

confidence: 99%

STAT3 and HIF1α Signaling Drives Oncogenic Cellular Phenotypes in Malignant Peripheral Nerve Sheath Tumors

Rad

Dodd

Thomas

et al. 2015

Molecular Cancer Research

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Therapeutic options are limited for neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNST) and clinical trials using drug agents have so far been unsuccessful. This lack of clinical success is likely attributed to high levels of intratumoral molecular heterogeneity and variations in signal transduction within MPNSTs. To better explore the variance of malignant signaling properties within heterogeneous MPNSTs, four MPNST cell lines (ST8814, S462, S1844.1, and S1507.2) were used. The data demonstrate that small-molecule inhibition of the MET proto-oncogene and mTOR had variable outcome when preventing wound healing, cell migration, and invasion, with the S462 cells being highly resistant to both. Of interest, targeted inhibition of the STAT3 transcription factor suppressed wound healing, cell migration, invasion, and tumor formation in all four MPNST lines, which demonstrates that unlike MET and mTOR, STAT3 functions as a common driver of tumorigenesis in NF1-MPNSTs. Of clinical importance, STAT3 knockdown was sufficient to block the expression of hypoxiainducible factor (HIF)1a, HIF2a, and VEGF-A in all four MPNST lines. Finally, the data demonstrate that wound healing, cell migration, invasion, and tumor formation through STAT3 are highly dependent on HIF signaling, where knockdown of HIF1a ablated these oncogenic facets of STAT3.Implications: This research reveals that aberrant STAT3 and HIF1a activity drives tumor progression in MPNSTs, indicating that inhibition of the STAT3/HIF1a/VEGF-A signaling axis is a viable treatment strategy.

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“…Current treatment options are restricted to complete surgical resection with clear margins; however, the local recurrence of MPNSTs is high (from 32% to 65%; ref. 9).…”

Section: Introductionmentioning

confidence: 99%

STAT3 and HIF1α Signaling Drives Oncogenic Cellular Phenotypes in Malignant Peripheral Nerve Sheath Tumors

Rad

Dodd

Thomas

et al. 2015

Molecular Cancer Research

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“…There are many reports regarding the utility and limits of FDG-PET for neurogenic tumors. It is known that benign neurogenic tumors often show high FDG accumulation based on the cell density (10,16,17,20,21).…”

Section: Discussionmentioning

confidence: 99%

Correlations between F-18 FDG PET/CT and pathological findings in soft tissue lesions

et al. 2013

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“…There have been few large studies about survival and those reporting 5-year survival lack consistency, with survival rates in the range of 39% -85%. Few studies have suggested NFI as an independent indicator of poor prognosis in MPNSTs [19]. A combination of clinical, pathological, and immunohistochemistry helps in diagnosing of these tumors.…”

Section: H M Hendam Et Al Open Journal Of Modern Neurosurgerymentioning

confidence: 99%

Surgical Approaches to Large Peripheral Nerve Sheets Tumors

Hendam¹,

Samouly²,

Behairy³

2018

OJMN

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Peripheral nerve sheath tumors (PNSTs) are not rare tumors. Its sound management is complete surgical excision. The aim of this study was to describe clinical presentation, accuracy of different investigations and ideal surgical approaches in relation to outcomes. The study is a prospective and included 26 surgically treated large PNSTs in 22 patients operated through different surgical approaches according to the site of the tumors. The fellow up period was 6 -60 months. The mean age was 41.8 years, 9 were males and 13 were females. The common presentations were pain in 12 lesions, swelling in 8 lesions, neural deficits in 4 lesions and positive Tinel's test in 2 lesions. These lesions were excised through 6 surgical approaches. Histopathological examination showed 20 benign and 6 malignant lesions. Five cases of malignant peripheral nerve sheet tumors (MPNSTs) had local recurrent, 4 cases had distant metastasis, 4 cases received chemotherapy and radiotherapy, and 4 cases were died in the postoperative fellow up period. It was concluded that surgical approaches to the PNSTs, depends on their locations. Adequate exposure with minimal dissection minimized the neurological deficit and decreased rate of local recurrence.

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Survival in Malignant Peripheral Nerve Sheath Tumours: A Comparison between Sporadic and Neurofibromatosis Type 1-Associated Tumours

Cited by 125 publications

References 23 publications

STAT3 and HIF1α Signaling Drives Oncogenic Cellular Phenotypes in Malignant Peripheral Nerve Sheath Tumors

STAT3 and HIF1α Signaling Drives Oncogenic Cellular Phenotypes in Malignant Peripheral Nerve Sheath Tumors

Correlations between F-18 FDG PET/CT and pathological findings in soft tissue lesions

Surgical Approaches to Large Peripheral Nerve Sheets Tumors

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