Poor prognosis despite aggressive treatment in adults with intramedullary spinal cord glioblastoma

Liu, Ann; Sankey, Eric W.; Bettegowda, Chetan; Burger, Peter C.; Jallo, George I.; Groves, Mari L.

doi:10.1016/j.jocn.2015.05.008

Cited by 20 publications

(16 citation statements)

References 30 publications

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“…Although many drugs have been identified and used to treat glioblastoma patients, their value in increasing progression-free survival or overall survival remains limited [2,3,23]. One reason for the limited efficacy of anti-glioblastoma drugs may be that a single glioblastoma lesion often contains both WT and mutated p53 cancer cells [24].…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Peptide TP4 Induces ROS-Mediated Necrosis by Triggering Mitochondrial Dysfunction in Wild-Type and Mutant p53 Glioblastoma Cells

Pan²,

Chen

2019

Cancers

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Antimicrobial peptide tilapia piscidin 4 (TP4) from Oreochromis niloticus exhibits potent bactericidal and anti-tumorigenic effects. In a variety of cancers, the mutation status of p53 is a decisive factor for therapeutic sensitivity. Therefore, we investigated the impact of p53 status on TP4-induced cytotoxicity in glioblastoma cell lines and the molecular mechanisms that govern cytotoxic effects. Both U87MG (wild-type/WT p53) and U251 (mutant p53) glioblastoma cell lines were sensitive to TP4-induced cytotoxicity. The necrosis inhibitors Necrostatin-1 and GSK’872 attenuated TP4-induced cytotoxicity, and TP4 treatment induced the release of cyclophilin A, a biomarker of necrosis. Moreover, TP4 induced mitochondrial hyperpolarization and dysfunction, which preceded the elevation of intracellular reactive oxygen species, DNA damage, and necrotic cell death in both U87MG and U251 glioblastoma cells. p38 was also activated by TP4, but did not contribute to cytotoxicity. SB202190, a specific p38 inhibitor, enhanced TP4-induced oxidative stress, mitochondrial dysfunction, and cytotoxicity, suggesting a protective role of p38. Furthermore, TP4-induced cytotoxicity, oxidative stress, phosphorylation of p38, and DNA damage were all attenuated by the mitochondrial-targeted reactive oxygen species (ROS) scavenger MitoTEMPO, or the reactive oxygen species scavenger N-acetyl-L-cysteine. Based on these data, we conclude that TP4 induces necrosis in both WT and mutant p53 glioblastoma cells through a mitochondrial ROS-dependent pathway.

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Section: Discussionmentioning

confidence: 99%

Antimicrobial Peptide TP4 Induces ROS-Mediated Necrosis by Triggering Mitochondrial Dysfunction in Wild-Type and Mutant p53 Glioblastoma Cells

Pan²,

Chen

2019

Cancers

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“…Given the known poor prognosis of these tumors , not surprisingly, the few surviving patients in our cohort had been diagnosed the most recently (see Table ). Spinal cord GBMs originated in cervicomedullary and upper cervical regions in 3 patients, and C7‐T1, T12‐L2 and T8‐T12, lumbar region in one each, underscoring the diversity of anatomical levels of cord involvement seen with these tumors (Figure A).…”

Section: Correspondencementioning

confidence: 99%

“…Rarity of GBMs in either optic chiasm or spinal cord (<1–3% of all GBMs) limits study size at any one institution and most are thus case reports or small cohorts, such as five spinal cord GBMs in the most recent series . We conducted a case search of departmental databases, 2006–present, and identified biopsies from seven spinal cord and two optic nerve GBMs from our institution (UCHSC).…”

Section: Correspondencementioning

confidence: 99%

Genetics of Glioblastomas in Rare Anatomical Locations: Spinal Cord and Optic Nerve

et al. 2015

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“…16 The general treatment paradigm includes maximum safe resection as the primary treatment 17 ; however, the true value of aggressive resection in patients with higher-grade disease is unknown, as these tumors are more infiltrative and have poorly defined resection planes. 18,19 Therefore, in clinical practice, patients with WHO grade I astrocytomas undergo primary resection, whereas those with higher-grade tumors often undergo biopsy alone. Adjuvant therapy recommendations are based on the extent of surgery, disease course extent (initial or recurrent disease), performance status, age of the patient, and WHO grade.…”

Section: Intramedullary Spinal Cord Tumorsmentioning

confidence: 99%

Updates in the management of intradural spinal cord tumors: a radiation oncology focus

et al. 2019

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Primary spinal cord tumors represent a hetereogeneous group of central nervous system malignancies whose management is complex given the relatively uncommon nature of the disease and variety of tumor subtypes, functional neurologic deficits from the tumor, and potential morbidities associated with definitive treatment. Advances in neuroimaging; integration of diagnostic, prognostic, and predictive molecular testing into tumor classification; and developments in neurosurgical techniques have refined the current role of radiotherapy in the multimodal management of patients with primary spinal cord tumors, and corroborated the need for prospective, multidisciplinary discussion and treatment decision making. Radiotherapeutic technological advances have dramatically improved the entire continuum from treatment planning to treatment delivery, and the development of stereotactic radiosurgery and proton radiotherapy provides new radiotherapy options for patients treated in the definitive, adjuvant, or salvage setting. The objective of this comprehensive review is to provide a contemporary overview of the management of primary intradural spinal cord tumors, with a focus on radiotherapy.

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Poor prognosis despite aggressive treatment in adults with intramedullary spinal cord glioblastoma

Cited by 20 publications

References 30 publications

Antimicrobial Peptide TP4 Induces ROS-Mediated Necrosis by Triggering Mitochondrial Dysfunction in Wild-Type and Mutant p53 Glioblastoma Cells

Antimicrobial Peptide TP4 Induces ROS-Mediated Necrosis by Triggering Mitochondrial Dysfunction in Wild-Type and Mutant p53 Glioblastoma Cells

Genetics of Glioblastomas in Rare Anatomical Locations: Spinal Cord and Optic Nerve

Updates in the management of intradural spinal cord tumors: a radiation oncology focus

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