Scholars@Duke
Stephen Thomas Keir

Stephen Thomas Keir

Professor in Neurosurgery
Neurosurgery, Neuro-Oncology
keir0001@mc.duke.edu
Box 3624 Med Ctr, Durham, NC 27710
231 Baker House, Durham, NC 27710

Selected Publications

The Neo-Open Reading Frame Peptides That Comprise the Tumor Framome Are a Rich Source of Neoantigens for Cancer Immunotherapy.

Journal Article Cancer Immunol Res · June 4, 2024 Identification of immunogenic cancer neoantigens as targets for therapy is challenging. Here, we integrate the whole-genome and long-read transcript sequencing of cancers to identify the collection of neo-open reading frame peptides (NOP) expressed in tumo ... Full text Link to item Cite

Interplay between ATRX and IDH1 mutations governs innate immune responses in diffuse gliomas.

Journal Article Nat Commun · January 25, 2024 Stimulating the innate immune system has been explored as a therapeutic option for the treatment of gliomas. Inactivating mutations in ATRX, defining molecular alterations in IDH-mutant astrocytomas, have been implicated in dysfunctional immune signaling. ... Full text Link to item Cite

A neural tract-inspired conduit for facile, on-demand biopsy of glioblastoma.

Journal Article Neurooncol Adv · 2024 BACKGROUND: A major hurdle to effectively treating glioblastoma (GBM) patients is the lack of longitudinal information about tumor progression, evolution, and treatment response. METHODS: In this study, we report the use of a neural tract-inspired conduit ... Full text Link to item Cite

Repurposing Clemastine to Target Glioblastoma Cell Stemness.

Journal Article Cancers (Basel) · September 18, 2023 Brain tumor-initiating cells (BTICs) and tumor cell plasticity promote glioblastoma (GBM) progression. Here, we demonstrate that clemastine, an over-the-counter drug for treating hay fever and allergy symptoms, effectively attenuated the stemness and suppr ... Full text Link to item Cite

Cancer-associated SMARCAL1 loss-of-function mutations promote alternative lengthening of telomeres and tumorigenesis in telomerase-negative glioblastoma cells.

Journal Article Neuro Oncol · September 5, 2023 BACKGROUND: Telomere maintenance mechanisms are required to enable the replicative immortality of malignant cells. While most cancers activate the enzyme telomerase, a subset of cancers uses telomerase-independent mechanisms termed alternative lengthening ... Full text Link to item Cite

Interplay between ATRX and IDH1 mutations governs innate immune responses in diffuse gliomas.

Journal Article bioRxiv · April 21, 2023 Stimulating the innate immune system has been explored as a therapeutic option for the treatment of gliomas. Inactivating mutations in ATRX , defining molecular alterations in IDH -mutant astrocytomas, have been implicated in dysfunctional immune signaling ... Full text Link to item Cite

Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation.

Journal Article J Immunother Cancer · January 2023 BACKGROUND: While major advances have been made in improving the quality of life and survival of children with most forms of medulloblastoma (MB), those with MYC-driven tumors (Grp3-MB) still suffer significant morbidity and mortality. There is an urgent n ... Full text Link to item Cite

Antitumor Activity of a Mitochondrial-Targeted HSP90 Inhibitor in Gliomas.

Journal Article Clin Cancer Res · May 13, 2022 PURPOSE: To investigate the antitumor activity of a mitochondrial-localized HSP90 inhibitor, Gamitrinib, in multiple glioma models, and to elucidate the antitumor mechanisms of Gamitrinib in gliomas. EXPERIMENTAL DESIGN: A broad panel of primary and temozo ... Full text Link to item Cite

Cold Plasma Discharge Tube Enhances Antitumoral Efficacy of Temozolomide.

Journal Article ACS Appl Bio Mater · April 18, 2022 Glioblastoma (GBM) is a fatal human brain tumor with a low survival rate. Temozolomide (TMZ) has been widely used in GBM therapy with noticeable side effects. Cold plasma is an ionized gas that is generated near room temperature. Here, we demonstrated the ... Full text Link to item Cite

A Modified Nucleoside 6-Thio-2'-Deoxyguanosine Exhibits Antitumor Activity in Gliomas.

Journal Article Clin Cancer Res · December 15, 2021 PURPOSE: To investigate the therapeutic role of a novel telomere-directed inhibitor, 6-thio-2'-deoxyguanosine (THIO) in gliomas both in vitro and in vivo. EXPERIMENTAL DESIGN: A panel of human and mouse glioma cell lines was used to test therapeutic effica ... Full text Link to item Cite

MTAP Loss Promotes Stemness in Glioblastoma and Confers Unique Susceptibility to Purine Starvation.

Journal Article Cancer Res · July 1, 2019 Homozygous deletion of methylthioadenosine phosphorylase (MTAP) is one of the most frequent genetic alterations in glioblastoma (GBM), but its pathologic consequences remain unclear. In this study, we report that loss of MTAP results in profound epigenetic ... Full text Link to item Cite

Synergistic antitumor effects of 9.2.27-PE38KDEL and ABT-737 in primary and metastatic brain tumors.

Journal Article PLoS One · 2019 Standard treatment, unfortunately, yields a poor prognosis for patients with primary or metastatic cancers in the central nervous system, indicating a necessity for novel therapeutic agents. Immunotoxins (ITs) are a class of promising therapeutic candidate ... Full text Open Access Link to item Cite

Bevacizumab, irinotecan, temozolomide, tyrosine kinase inhibition, and MEK inhibition are effective against pleomorphic xanthoastrocytoma regardless of V600E status.

Journal Article J Neurooncol · November 2018 INTRODUCTION: Pleomorphic xanthoastrocytoma (PXA) is a rare Grade II and III glioma. Surgical resection is the mainstay of treatment, however, adjuvant therapy is sometimes necessary. Given the rarity of PXA, chemotherapeutic efficacy data is limited. The ... Full text Link to item Cite

A Rationally Designed Fully Human EGFRvIII:CD3-Targeted Bispecific Antibody Redirects Human T Cells to Treat Patient-derived Intracerebral Malignant Glioma.

Journal Article Clin Cancer Res · August 1, 2018 Purpose: Conventional therapy for malignant glioma fails to specifically target tumor cells. In contrast, substantial evidence indicates that if appropriately redirected, T cells can precisely eradicate tumors. Here we report the rational development of a ... Full text Link to item Cite

Sym004-induced EGFR elimination is associated with profound anti-tumor activity in EGFRvIII patient-derived glioblastoma models.

Journal Article J Neurooncol · July 2018 BACKGROUND: Sym004 is a mixture of two monoclonal antibodies (mAbs), futuximab and modotuximab, targeting non-overlapping epitopes on the epidermal growth factor receptor (EGFR). Previous studies have shown that Sym004 is more efficient at inducing interna ... Full text Open Access Link to item Cite

Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling.

Journal Article Nature · January 4, 2018 Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemothe ... Full text Link to item Cite

Validation of an Immunohistochemistry Assay for Detection of CD155, the Poliovirus Receptor, in Malignant Gliomas.

Journal Article Arch Pathol Lab Med · December 2017 CONTEXT: - The oncolytic polio-rhinovirus recombinant (PVSRIPO) has demonstrated promise in currently ongoing phase I/II clinical trials against recurrent glioblastoma and was granted breakthrough therapy designation by the Food and Drug Administration/Cen ... Full text Link to item Cite

The role of angiogenesis in Group 3 medulloblastoma pathogenesis and survival.

Journal Article Neuro Oncol · September 1, 2017 BACKGROUND: Of the 4 medulloblastoma subgroups, Group 3 is the most aggressive but the importance of angiogenesis is unknown. This study sought to determine the role of angiogenesis and identify clinically relevant biomarkers of tumor vascularity and survi ... Full text Link to item Cite

A cross sectional analysis from a single institution's experience of psychosocial distress and health-related quality of life in the primary brain tumor population.

Journal Article J Neurooncol · September 2017 Primary brain tumor patients experience high levels of distress. The purpose of this cross-sectional, retrospective study is to evaluate the level and different sources of psychosocial distress and how these pertain to health-related quality of life (HRQoL ... Full text Link to item Cite

Initial testing (stage 1) of the curaxin CBL0137 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · April 2017 BACKGROUND: CBL0137 is a novel drug that modulates FAcilitates Chromatin Transcription (FACT), resulting in simultaneous nuclear factor-κB suppression, heat shock factor 1 suppression and p53 activation. CBL0137 has demonstrated antitumor effects in animal ... Full text Link to item Cite

Initial testing of VS-4718, a novel inhibitor of focal adhesion kinase (FAK), against pediatric tumor models by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · April 2017 VS-4718, a novel inhibitor of focal adhesion kinase (FAK), was tested against the Pediatric Preclinical Testing Program's (PPTP's) in vitro cell line panel and showed a median relative IC50 of 1.22 μM. VS-4718 was tested in vivo against the PPTP xenograft ... Full text Link to item Cite

Initial Testing (Stage 1) of MK-8242-A Novel MDM2 Inhibitor-by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · October 2016 BACKGROUND: MK-8242 is an inhibitor of MDM2 that stabilizes the tumor suppressor TP53 and induces growth arrest or apoptosis downstream of TP53 induction. PROCEDURES: MK-8242 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell ... Full text Link to item Cite

Evaluation of Alternative In Vivo Drug Screening Methodology: A Single Mouse Analysis.

Journal Article Cancer Res · October 1, 2016 Traditional approaches to evaluating antitumor agents using human tumor xenograft models have generally used cohorts of 8 to 10 mice against a limited panel of tumor models. An alternative approach is to use fewer animals per tumor line, allowing a greater ... Full text Link to item Cite

A Therapeutic Antibody for Cancer, Derived from Single Human B Cells.

Journal Article Cell Rep · May 17, 2016 Some patients with cancer never develop metastasis, and their host response might provide cues for innovative treatment strategies. We previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. ... Full text Open Access Link to item Cite

Initial Testing of NSC 750854, a Novel Purine Analog, Against Pediatric Tumor Models by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · March 2016 BACKGROUND: NSC 750854 is a purine analog with an antitumor activity profile distinctive from that of other anticancer purines. It has shown significant activity against adult cancer preclinical models. PROCEDURE: NSC 750854 was tested against the Pediatri ... Full text Link to item Cite

Pharmacodynamic and genomic markers associated with response to the XPO1/CRM1 inhibitor selinexor (KPT-330): A report from the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · February 2016 BACKGROUND: Selinexor (KPT-330) is an inhibitor of the major nuclear export receptor, exportin 1 (XPO1, also termed chromosome region maintenance 1, CRM1) that has demonstrated activity in preclinical models and clinical activity against several solid and ... Full text Link to item Cite

MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.

Journal Article Cancer Cell · January 11, 2016 The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here, we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit t ... Full text Open Access Link to item Cite

Phosphorylation of Glutathione S-Transferase P1 (GSTP1) by Epidermal Growth Factor Receptor (EGFR) Promotes Formation of the GSTP1-c-Jun N-terminal kinase (JNK) Complex and Suppresses JNK Downstream Signaling and Apoptosis in Brain Tumor Cells.

Journal Article J Biol Chem · December 25, 2015 Under normal physiologic conditions, the glutathione S-transferase P1 (GSTP1) protein exists intracellularly as a dimer in reversible equilibrium with its monomeric subunits. In the latter form, GSTP1 binds to the mitogen-activated protein kinase, JNK, and ... Full text Link to item Cite

Dynamic treatment effect (DTE) curves reveal the mode of action for standard and experimental cancer therapies.

Journal Article Oncotarget · June 10, 2015 We present a method for estimating the empirical dynamic treatment effect (DTE) curves from tumor growth delay (TGD) studies. This improves on current common methods of TGD analysis, such as T/C ratio and doubling times, by providing a more detailed treatm ... Full text Link to item Cite

Initial testing (stage 1) of BAL101553, a novel tubulin binding agent, by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · June 2015 BAL101553 is a highly water soluble prodrug of BAL27862 that arrests tumor cell proliferation and induces cell death in cancer cells through disruption of the microtubule network. In vitro BAL27862 demonstrated potent activity, with the median relative IC5 ... Full text Link to item Cite

Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: implications for drug development.

Journal Article J Neurochem · June 2015 The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts (PDGX) has not been performed. In the present study, we characte ... Full text Link to item Cite

Synergistic activity of PARP inhibition by talazoparib (BMN 673) with temozolomide in pediatric cancer models in the pediatric preclinical testing program.

Journal Article Clin Cancer Res · February 15, 2015 PURPOSE: Inhibitors of PARP, an enzyme involved in base excision repair, have demonstrated single-agent activity against tumors deficient in homologous repair processes. Ewing sarcoma cells are also sensitive to PARP inhibitors, although the mechanism is n ... Full text Link to item Cite

Initial testing (stage 1) of the PARP inhibitor BMN 673 by the pediatric preclinical testing program: PALB2 mutation predicts exceptional in vivo response to BMN 673.

Journal Article Pediatr Blood Cancer · January 2015 BACKGROUND: BMN 673 is a potent inhibitor of poly-ADP ribose polymerase (PARP) that is in clinical testing with a primary focus on BRCA-mutated cancers. BMN 673 is active both through inhibiting PARP catalytic activity and by tightly trapping PARP to DNA a ... Full text Link to item Cite

Profiling Hsp90 differential expression and the molecular effects of the Hsp90 inhibitor IPI-504 in high-grade glioma models.

Journal Article J Neurooncol · December 2014 Retaspimycin hydrochloride (IPI-504), an Hsp90 (heat shock protein 90) inhibitor, has shown activity in multiple preclinical cancer models, such as lung, breast and ovarian cancers. However, its biological effects in gliomas and normal brain derived cellul ... Full text Link to item Cite

Initial solid tumor testing (stage 1) of AZD1480, an inhibitor of Janus kinases 1 and 2 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · November 2014 BACKGROUND: AZD1480 is an ATP competitive inhibitor of Janus kinases 1 and 2 (JAK1, 2) that has been shown to inhibit the growth of solid tumor models. This agent was selected for testing the putative role of JAK/STAT signaling in the standard PPTP solid t ... Full text Link to item Cite

miR-33a promotes glioma-initiating cell self-renewal via PKA and NOTCH pathways.

Journal Article J Clin Invest · October 2014 Glioblastoma (GBM) is the most common and lethal brain tumor in adults. Glioma-initiating cells (GICs) are stem-like cells that have been implicated in glioblastoma progression and recurrence; however, the distinct properties of GICs and non-GICs within GB ... Full text Link to item Cite

Erratum

Journal Article Pediatric Blood & Cancer · September 2014 Full text Cite

Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · August 2014 MLN0128 is an investigational small molecule ATP-competitive inhibitor of the serine/threonine kinase mTOR. MLN0128 was tested against the in vitro panel at concentrations ranging from 0.1 nM to 1 μM and against the PPTP in vivo panels at a dose of 1 mg/kg ... Full text Link to item Cite

Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · August 2014 PF-03084014, a γ-secretase inhibitor, was tested against the PPTP in vitro cell line panel (1.0 nM to 10 μM) and against the in vivo xenograft panels (administered orally twice daily on Days 1-7 and 15-21). PF-03084014 demonstrated limited in vitro activit ... Full text Link to item Cite

Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas.

Journal Article Oncotarget · March 30, 2014 Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or o ... Full text Open Access Link to item Cite

Initial testing (stage 1) of the histone deacetylase inhibitor, quisinostat (JNJ-26481585), by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · February 2014 BACKGROUND: Quisinostat (JNJ-26481585) is a second-generation pyrimidyl-hydroxamic acid histone deacetylase (HDAC) inhibitor with high cellular potency towards Class I and II HDACs. Quisinostat was selected for clinical development as it showed prolonged p ... Full text Link to item Cite

Initial testing (stage 1) of the Polo-like kinase inhibitor volasertib (BI 6727), by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · January 2014 BACKGROUND: Volasertib (BI 6727) is a potent inhibitor of Polo-like kinase 1 (Plk1), that is overexpressed in several childhood cancers and cell lines. Because of its novel mechanism of action, volasertib was evaluated through the PPTP. PROCEDURES: Volaser ... Full text Link to item Cite

KMT2D maintains neoplastic cell proliferation and global histone H3 lysine 4 monomethylation.

Journal Article Oncotarget · November 2013 KMT2D (lysine (K)-specific methyltransferase 2D), formerly named MLL2 (myeloid/lymphoid or mixed-lineage leukemia 2, also known as ALR/MLL4), is a histone methyltransferase that plays an important role in regulating gene transcription. In particular, it ta ... Full text Link to item Cite

Initial testing (Stage 1) of the antibody-maytansinoid conjugate, IMGN901 (Lorvotuzumab mertansine), by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · November 2013 BACKGROUND: IMGN901 (lorvotuzumab mertansine) is an antibody-drug conjugate composed of a humanized antibody that specifically binds to CD56 (NCAM, neural cell adhesion molecule) and that is conjugated to the maytansinoid, DM1 (a microtubule targeting agen ... Full text Link to item Cite

The integrated landscape of driver genomic alterations in glioblastoma.

Journal Article Nat Genet · October 2013 Glioblastoma is one of the most challenging forms of cancer to treat. Here we describe a computational platform that integrates the analysis of copy number variations and somatic mutations and unravels the landscape of in-frame gene fusions in glioblastoma ... Full text Link to item Cite

Construction of an immunotoxin, D2C7-(scdsFv)-PE38KDEL, targeting EGFRwt and EGFRvIII for brain tumor therapy.

Journal Article Clin Cancer Res · September 1, 2013 PURPOSE: The EGF receptor gene (EGFR) is most frequently amplified and overexpressed, along with its deletion mutant, EGFRvIII, in glioblastoma. We tested the preclinical efficacy of the recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL, which is reactive wi ... Full text Link to item Cite

Initial testing (stage 1) of eribulin, a novel tubulin binding agent, by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · August 2013 BACKGROUND: Antimitotic agents are essential components for curative therapy of pediatric acute leukemias and many solid tumors. Eribulin is a novel agent that differs from both Vinca alkaloids and taxanes in its mode of binding to tubulin polymers. PROCED ... Full text Link to item Cite

Initial testing (stage 1) of ganetespib, an Hsp90 inhibitor, by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · July 2013 Ganetespib, an Hsp90 inhibitor, was tested against the PPTP in vitro cell line panel and selected xenografts in vivo, including JAK2- and BRAF-mutated models. Ganetespib demonstrated potent in vitro cytotoxic activity (median rIC50 8.8 nM, range 4.4-27.1 n ... Full text Link to item Cite

Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors.

Journal Article Int J Cancer · May 15, 2013 Our study demonstrates the glioma tumor antigen podoplanin to be present at very high levels (>90%) in both glioblastoma (D2159MG, D08-0308MG and D08-0493MG) and medulloblastoma (D283MED, D425MED and DAOY) xenografts and cell line. We constructed a novel r ... Full text Link to item Cite

Initial testing (stage 1) of temozolomide by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · May 2013 BACKGROUND: The DNA methylating agent temozolomide was developed primarily for treatment of glioblastoma. However, preclinical data have suggested a broader application for treatment of childhood cancer. Temozolomide was tested against the PPTP solid tumor ... Full text Link to item Cite

Initial testing (stage 1) of the phosphatidylinositol 3' kinase inhibitor, SAR245408 (XL147) by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · May 2013 BACKGROUND: Activation of the PI3 kinase pathway occurs frequently in many adult cancers and is implicated in tumor cell proliferation, survival, and resistance to chemotherapy and radiotherapy. However, less is known regarding the relevance of this pathwa ... Full text Link to item Cite

Initial testing of the MDM2 inhibitor RG7112 by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · April 2013 BACKGROUND: RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis. RG7112 was selected for evaluation by the Pediatric Preclinical Tes ... Full text Link to item Cite

Exomic sequencing of four rare central nervous system tumor types.

Journal Article Oncotarget · April 2013 A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric ... Full text Link to item Cite

Reversing the Warburg effect as a treatment for glioblastoma.

Journal Article J Biol Chem · March 29, 2013 Glioblastoma multiforme (GBM), like most cancers, possesses a unique bioenergetic state of aerobic glycolysis known as the Warburg effect. Here, we documented that methylene blue (MB) reverses the Warburg effect evidenced by the increasing of oxygen consum ... Full text Link to item Cite

The integrated landscape of driver genomic alterations in glioblastoma

Journal Article Nature Genetics · 2013 Glioblastoma is one of the most challenging forms of cancer to treat. Here we describe a computational platform that integrates the analysis of copy number variations and somatic mutations and unravels the landscape of in-frame gene fusions in glioblastoma ... Full text Cite

Mibefradil, a novel therapy for glioblastoma multiforme: cell cycle synchronization and interlaced therapy in a murine model.

Journal Article J Neurooncol · January 2013 Glioblastoma multiforme (GBM) is a devastating disease with a dismal prognosis and a very limited response to treatment. The current standard of care for GBM usually consists of surgery, radiation and chemotherapy with the alkylating agent temozolomide, al ... Full text Link to item Cite

Affinity-matured recombinant immunotoxin targeting gangliosides 3'-isoLM1 and 3',6'-isoLD1 on malignant gliomas.

Journal Article MAbs · 2013 About 60 percent of glioblastomas highly express the gangliosides 3'-isoLM1 and 3',6'-isoLD1 on the cell surface, providing ideal targets for brain tumor immunotherapy. A novel recombinant immunotoxin, DmAb14m-(scFv)-PE38KDEL (DmAb14m-IT), specific for the ... Full text Link to item Cite

Initial testing (stage 1) of the cyclin dependent kinase inhibitor SCH 727965 (dinaciclib) by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · December 15, 2012 BACKGROUND: SCH 727965 is a novel drug in clinical development that potently and selectively inhibits CDK1, CDK2, CDK5, and CDK9. The activity of SCH 727965 was evaluated against the PPTP's in vitro and in vivo panels. PROCEDURES: SCH 727965 was tested aga ... Full text Link to item Cite

Pilot study of the impact of massage therapy on sources and levels of distress in brain tumour patients.

Journal Article BMJ Support Palliat Care · December 2012 BACKGROUND: Patients with brain tumours report elevated levels of distress across the disease course. Massage therapy is a commonly used complementary therapy and is employed in cancer care to reduce psychological stress and to improve quality of life (QoL ... Full text Link to item Cite

Mechanism of anti-glioma activity and in vivo efficacy of the cannabinoid ligand KM-233.

Journal Article J Neurooncol · November 2012 Glioblastoma multiforme (GBM) is the most common and devastating form of primary central nervous system malignancy. The prognosis for patients diagnosed with GBM is poor, having a median survival rate of 12-15 months. Despite modern advances in the develop ... Full text Link to item Cite

Initial testing (stage 1) of SGI-1776, a PIM1 kinase inhibitor, by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · October 2012 The PIM kinase inhibitor, SGI-1776, was tested against the PPTP in vitro (1.0 nM-10 µM) and in vivo panels (148 mg/kg daily × 5 days for 3 weeks). SGI-1776 exhibited cytotoxic activity in vitro with a median relative IC(50) of 3.1 µM. SGI-1776 induced sign ... Full text Link to item Cite

Initial testing of the multitargeted kinase inhibitor pazopanib by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · September 2012 Pazopanib is an oral angiogenesis inhibitor targeting vascular growth factor receptor-1, -2, and -3, platelet derived growth factor receptor-α, platelet derived growth factor receptor-β, and KIT that has demonstrated activity against a variety of adult can ... Full text Link to item Cite

Testing of the Akt/PKB inhibitor MK-2206 by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · September 2012 BACKGROUND: MK-2206 is a small molecule allosteric inhibitor of Akt/PKB that is undergoing clinical trials for treatment of cancer. PROCEDURES: MK-2206 was tested against the PPTP in vitro panel using a 96-hour exposure (1.0 nM-10 µM), and in vivo using th ... Full text Link to item Cite

Initial testing of JNJ-26854165 (Serdemetan) by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · August 2012 JNJ-26854165 was originally developed as an activator of p53 capable of inducing apoptosis in cancer cell lines. In vitro, JNJ-26854165 demonstrated cytotoxic activity. The ALL cell line panel had a significantly lower median IC(50) (0.85 µM) than the rema ... Full text Link to item Cite

Initial testing of the investigational NEDD8-activating enzyme inhibitor MLN4924 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · August 2012 BACKGROUND: MLN4924 is an investigational first-in-class small molecule inhibitor of NEDD8-activating enzyme (NAE). NAE is an essential component of the NEDD8 conjugation pathway, controlling the activity of a subset of ubiquitin-proteasome system (UPS) E3 ... Full text Link to item Cite

Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · July 15, 2012 AT13387, a non-geldanamycin inhibitor of heat-shock protein 90 (HSP90), was tested against the PPTP in vitro panel (1.0 nM to 10 µM) and against the PPTP in vivo panels (40 or 60 mg/kg) administered orally twice weekly. In vitro AT13387 showed a median EC( ... Full text Link to item Cite

Initial testing of the CENP-E inhibitor GSK923295A by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · June 2012 BACKGROUND: The centromere kinesin motor protein CENP-E plays a crucial role in mitosis, and is an appealing molecular target in cancer. GSK923295A is an allosteric inhibitor of CENP-E that is undergoing clinical evaluation. PROCEDURES: GSK923295A was eval ... Full text Link to item Cite

Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling.

Journal Article Pediatr Blood Cancer · May 2012 RO4929097 is a potent and selective inhibitor of γ-secretase and as a result is able to inhibit Notch pathway signaling. The activity of RO4929097 was evaluated against the in vivo panels of the Pediatric Preclinical Testing Program (PPTP). RO4929097 induc ... Full text Link to item Cite

Combination testing (Stage 2) of the Anti-IGF-1 receptor antibody IMC-A12 with rapamycin by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · May 2012 BACKGROUND: IMC-A12, a fully human antibody that blocks ligand binding to the Type 1 insulin-like growth factor receptor, and rapamycin, a selective inhibitor of mTORC1 signaling, have both demonstrated significant antitumor activity against PPTP solid tum ... Full text Link to item Cite

Initial testing (stage 1) of LCL161, a SMAC mimetic, by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · April 2012 LCL161, a SMAC mimetic, was tested against the PPTP in vitro panel (1.0 nM to 10.0 µM) and the PPTP in vivo panels (30 or 75 mg/kg [solid tumors] or 100 mg/kg [ALL]) administered orally twice in a week. LCL161 showed a median relative IC(50) value of >10 µ ... Full text Link to item Cite

Combination testing of cediranib (AZD2171) against childhood cancer models by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · April 2012 BACKGROUND: Cediranib (AZD2171) is a potent small molecule inhibitor of vascular endothelial growth factor (VEGF) receptors. Cediranib has demonstrated single agent activity in several adult cancers and is being studied in combination with standard cytotox ... Full text Link to item Cite

Initial testing (stage 1) of the mTOR kinase inhibitor AZD8055 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · February 2012 BACKGROUND: AZD8055 is a small molecule ATP-competitive inhibitor of the serine/threonine kinase mTOR that regulates cap-dependent translation through the mTORC1 complex and Akt activation through the mTORC2 complex. Procedures AZD8055 was tested against t ... Full text Link to item Cite

Testing of the topoisomerase 1 inhibitor Genz-644282 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · February 2012 BACKGROUND: Genz-644282 is a novel non-camptothecin topoisomerase I poison that is in clinical development. PROCEDURES: Genz-644282 was tested against the PPTP in vitro panel (0.1 nM to 1 µM), and in vivo using three times per week × 2 schedule repeated at ... Full text Link to item Cite

Efficacy and pharmacokinetic/pharmacodynamic evaluation of the Aurora kinase A inhibitor MLN8237 against preclinical models of pediatric cancer.

Journal Article Cancer Chemother Pharmacol · November 2011 PURPOSE: To gain a greater understanding of the potential of the Aurora kinase A inhibitor MLN8237 in the treatment of pediatric malignancies. METHODS: The activity of MLN8237 was evaluated against 28 neuroblastoma and Ewing sarcoma cell lines, and its in ... Full text Link to item Cite

Initial testing of lenalidomide by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · October 2011 BACKGROUND: Lenalidomide, a novel immunomodulatory agent, is reported to modulate stem cell differentiation, and have direct antiproliferative activity as well as inhibit inflammation and hyperalgesia. On the basis of this varied pharmacological profile, l ... Full text Link to item Cite

Initial testing of the hypoxia-activated prodrug PR-104 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · September 2011 BACKGROUND: PR-104 is rapidly hydrolyzed to PR-104A in vivo, which is activated by reduction to the corresponding 5-hydroxylamine (PR-104H) and amine (PR-104M) to produce DNA interstrand cross-links. PR-104 activation can occur via hypoxia-dependent reduct ... Full text Link to item Cite

Initial testing (stage 1) of the polyamine analog PG11047 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · August 2011 BACKGROUND: PG11047 is a novel conformationally restricted analog of the natural polyamine, spermine that lowers cellular endogenous polyamine levels and competitively inhibits natural polyamine functions leading to cancer cell growth inhibition. The activ ... Full text Link to item Cite

Affinity-matured anti-glycoprotein NMB recombinant immunotoxins targeting malignant gliomas and melanomas.

Journal Article Int J Cancer · July 1, 2011 Glycoprotein NMB (GPNMB), a transmembrane glycoprotein highly expressed in high-grade gliomas (HGGs), is an attractive target in cancer immunotherapy. We isolated a GPNMB-specific scFv clone, G49, from a human synthetic phage-display library. To obtain mut ... Full text Link to item Cite

Effect of massage therapy on stress levels and quality of life in brain tumor patients--observations from a pilot study.

Journal Article Support Care Cancer · May 2011 BACKGROUND: Patients with brain tumors report experiencing elevated levels of stress across the disease continuum. Massage therapy is a commonly used complementary therapy and is employed in cancer care to reduce psychological stress and to improve quality ... Full text Link to item Cite

Initial testing (stage 1) of the IGF-1 receptor inhibitor BMS-754807 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · April 2011 BACKGROUND: BMS-754807 is a small molecule ATP-competitive inhibitor of the type-1 insulin-like growth factor receptor currently in phase 1 clinical trials. PROCEDURES: BMS-754807 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro ... Full text Link to item Cite

Cellular redox modulator, ortho Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin, MnTnHex-2-PyP(5+) in the treatment of brain tumors.

Journal Article Anticancer Agents Med Chem · February 2011 Despite intensive efforts to improve multimodal treatment of brain tumor, survival remains limited. Current therapy consists of a combination of surgery, irradiation and chemotherapy with predisposition to long-term complications. Identifying novel targete ... Full text Link to item Cite

The genetic landscape of the childhood cancer medulloblastoma.

Journal Article Science · January 28, 2011 Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and micro ... Full text Link to item Cite

Initial testing (stage 1) of the Akt inhibitor GSK690693 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · December 15, 2010 BACKGROUND: GSK690693 is a small molecule ATP-competitive inhibitor of the pro-survival kinase Akt. Since Akt regulates multiple downstream targets including transcription factors, glycogen synthase 3, the pro-apoptotic protein Bad, as well as MDM2 and mTO ... Full text Link to item Cite

Corticorelin acetate, a synthetic corticotropin-releasing factor with preclinical antitumor activity, alone and with bevacizumab, against human brain tumor models.

Journal Article Anticancer Res · December 2010 BACKGROUND: Corticorelin acetate (CrA) is a synthetic form of corticotropin-releasing factor that is currently undergoing clinical trials in the treatment of peritumoral brain edema (PBE). This study preclinically investigated its potential as an antitumor ... Link to item Cite

Initial testing (stage 1) of the multi-targeted kinase inhibitor sorafenib by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · December 1, 2010 BACKGROUND: Sorafenib is an inhibitor of multiple kinases (e.g., VEGF receptors, PDGFR, FLT3, RET, BRAF, KIT) and is approved by FDA for treatment of two adult cancers. The activity of sorafenib was evaluated against the PPTP's in vitro and in vivo panels. ... Full text Link to item Cite

Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas.

Journal Article Nucl Med Biol · October 2010 INTRODUCTION: Podoplanin/aggrus is a mucin-like sialoglycoprotein that is highly expressed in malignant gliomas. Podoplanin has been reported to be a novel marker to enrich tumor-initiating cells, which are thought to resist conventional therapies and to b ... Full text Link to item Cite

Initial testing (stage 1) of AZD6244 (ARRY-142886) by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · October 2010 BACKGROUND: AZD6244 (ARRY-142886) is a potent small molecule inhibitor of MEK1/2 that is in phase 2 clinical development. PROCEDURES: AZD6244 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel (1 nM-10 microM). In vivo AZD62 ... Full text Link to item Cite

HDMX regulates p53 activity and confers chemoresistance to 3-bis(2-chloroethyl)-1-nitrosourea.

Journal Article Neuro Oncol · September 2010 Glioblastoma multiforme (GBM) is one of the deadliest tumors afflicting humans, and the mechanisms of its onset and progression remain largely undefined. Our attempts to elucidate its molecular pathogenesis through DNA copy-number analysis by genome-wide d ... Full text Link to item Cite

EGFR and EGFRvIII interact with PUMA to inhibit mitochondrial translocalization of PUMA and PUMA-mediated apoptosis independent of EGFR kinase activity.

Journal Article Cancer Lett · August 1, 2010 EGFR and its constitutively activated variant EGFRvIII are linked to glioblastoma resistance to therapy, the mechanisms underlying this association, however, are still unclear. We report that in glioblastoma, EGFR/EGFRvIII paradoxically co-expresses with p ... Full text Link to item Cite

Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · August 2010 BACKGROUND: Seneca Valley virus (NTX-010) is a non-recombinant, replication competent RNA virus that is undergoing phase 1 clinical trials in adults for tumors with neuroendocrine characteristics. Here we have evaluated the antitumor activity of NTX-010 ad ... Full text Link to item Cite

Initial testing of the aurora kinase A inhibitor MLN8237 by the Pediatric Preclinical Testing Program (PPTP).

Journal Article Pediatr Blood Cancer · July 15, 2010 BACKGROUND: MLN8237 is a small molecule inhibitor of Aurora Kinase A (AURKA) that is currently in early phase clinical testing. AURKA plays a pivotal role in centrosome maturation and spindle formation during mitosis. PROCEDURES: MLN8237 was tested against ... Full text Link to item Cite

Initial testing of a monoclonal antibody (IMC-A12) against IGF-1R by the Pediatric Preclinical Testing Program.

Journal Article Pediatr Blood Cancer · July 1, 2010 BACKGROUND: Many childhood malignancies including sarcomas, neuroblastoma, and Wilms tumor show the presence of both, active, type-1-insulin-like growth factor receptor (IGF-1R), and the autocrine production of its ligands IGF-1/IGF-2. IMC-A12 is a fully h ... Full text Link to item Cite

Initial testing of topotecan by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · May 2010 BACKGROUND: Topotecan is a small molecule DNA topoisomerase I poison, that has been successful in clinical trials against pediatric solid tumors and leukemias. Topotecan was evaluated against the Pediatric Preclinical Testing Program (PPTP) tumor panels as ... Full text Link to item Cite

Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer.

Journal Article J Appl Physiol (1985) · February 2010 Recent epidemiologic studies report that regular exercise may be associated with substantial reductions in cancer-specific and all-cause mortality following a breast cancer diagnosis. The mechanisms underlying this relationship have not been identified. We ... Full text Link to item Cite

Initial testing (stage 1) of mapatumumab (HGS-ETR1) by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · February 2010 Mapatumumab (HGS-ETR1) is a fully human IgG1 agonistic monoclonal antibody that exclusively targets and activates tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1). It was tested in vitro at concentrations from 0.01 to 100 micro ... Full text Link to item Cite

[Lu]-DOTA-Tyr-octreotate: A Potential Targeted Radiotherapeutic for the Treatment of Medulloblastoma.

Journal Article Curr Radiopharm · 2010 Medulloblastoma, the most common pediatric brain tumor, is difficult to treat because conventional therapeutic approaches result in significant toxicity to normal central nervous system tissues, compromising quality of life. Given the fact that medulloblas ... Full text Link to item Cite

Stage 2 combination testing of rapamycin with cytotoxic agents by the Pediatric Preclinical Testing Program.

Journal Article Mol Cancer Ther · January 2010 Rapamycin demonstrated broad-spectrum tumor growth inhibition activity against the in vivo panels of childhood tumors used in the Pediatric Preclinical Testing Program (PPTP). Here we have evaluated rapamycin combined with agents used frequently in the tre ... Full text Link to item Cite

Initial testing (stage 1) of the kinesin spindle protein inhibitor ispinesib by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · December 15, 2009 BACKGROUND: Ispinesib is a highly specific inhibitor of kinesin spindle protein (KSP, HsEg5), a mitotic kinesin required for separation of the spindle poles. Here we report the activity of ispinesib against the in vitro and in vivo panels of the Pediatric ... Full text Link to item Cite

Initial testing (stage 1) of lapatinib by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · October 2009 BACKGROUND: Lapatinib is a small molecule reversible tyrosine kinase inhibitor of EGFR and ErbB2 that shows in vitro and in vivo activity against a range of EGFR and ErbB2-dependent adult cancer cell lines and that has clinical efficacy against ErbB2-overe ... Full text Link to item Cite

Initial testing of aplidin by the pediatric pre-clinical testing program.

Journal Article Pediatr Blood Cancer · September 2009 Aplidin was tested in vitro at concentrations ranging from from 0.1 nM to 1.0 microM and in vivo at a dose of 0.6 mg/kg administered intraperitoneally on an every 4 days x 3-schedule that was repeated at day 21. In vitro, Aplidin was most active against ac ... Full text Link to item Cite

Initial testing (stage 1) of vorinostat (SAHA) by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · September 2009 Vorinostat, a histone deacetylase inhibitor, was evaluated against the in vitro and in vivo childhood solid tumor and leukemia models in the Pediatric Preclinical Testing Program (PPTP). In vitro testing was performed by the DIMSCAN cytotoxicity assay. In ... Full text Link to item Cite

Family appraisal of caregiving in a brain cancer model

Journal Article Journal of Hospice and Palliative Nursing · January 1, 2009 Caregivers of patients with brain tumors frequently provide care to a patient with a potentially short terminal disease trajectory. Understanding the impact of caregiving is important because caregivers are often called upon to make difficult decisions reg ... Full text Cite

Distress persists in long-term brain tumor survivors with glioblastoma multiforme.

Journal Article J Cancer Surviv · December 2008 INTRODUCTION: Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor. The prognosis for GBM patients is extremely poor with an estimated median survival of 12 months. Despite this statistic, a number of GBM patients are ... Full text Link to item Cite

An integrated genomic analysis of human glioblastoma multiforme.

Journal Article Science · September 26, 2008 Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. To identify the genetic alterations in GBMs, we sequenced 20,661 protein coding genes, determined the presence of amplifications and deletions using high-density oligonucleot ... Full text Link to item Cite

Initial testing of VNP40101M (Cloretazine) by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · September 2008 VNP40101M is a novel alkylating agent that yields two reactive compounds (a chloroethylating species and methylisocyanate) and has demonstrated activity against a wide spectrum of tumor xenografts. VNP40101M was tested against an in vivo panel of five pedi ... Full text Link to item Cite

Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · July 2008 BACKGROUND: Sunitinib is an orally bioavailable, multi-targeted tyrosine kinase inhibitor with selectivity for PDGF receptors, VEGF receptors, FLT3, and KIT. PROCEDURES: Sunitinib was tested at concentrations ranging from 0.1 nM to 1.0 microM against 23 ce ... Full text Link to item Cite

Stage 1 testing and pharmacodynamic evaluation of the HSP90 inhibitor alvespimycin (17-DMAG, KOS-1022) by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · July 2008 BACKGROUND: Alvespimycin (17-DMAG, KOS-1022), a potent small-molecule inhibitor of the protein chaperone Hsp90, is being developed as an anticancer agent because of the multiple Hsp90 client proteins involved in cancer cell growth and survival. PROCEDURES: ... Full text Link to item Cite

Screening for distress in patients with brain cancer using the NCCN's rapid screening measure.

Journal Article Psychooncology · June 2008 GOALS OF WORK: Patients with brain cancer are at a risk of experiencing elevated levels of distress due to the severe functional, neurocognitive, and neuropsychological sequelae of the disease. Using the National Comprehensive Cancer Network's Distress The ... Full text Link to item Cite

Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · June 2008 BACKGROUND: SCH 717454 (19D12) is a fully human antibody directed against the insulin-like growth factor 1 receptor (IGF-1R), which is implicated in the growth and metastatic phenotype of a broad range of malignancies. The activity of SCH 717454 was evalua ... Full text Link to item Cite

Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · June 2008 BACKGROUND: ABT-263 is a potent (K(i) < 1 nM) small-molecule BH3 mimetic that inhibits the antiapoptotic proteins Bcl-2, Bcl-x(L) and Bcl-w. The structurally related Bcl-2 inhibitor ABT-737 exhibits single-agent preclinical activity against lymphoma, small ... Full text Link to item Cite

Initial testing of dasatinib by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · June 2008 BACKGROUND: Dasatinib, a dual inhibitor of the src and abl tyrosine kinases, was recently approved by the Federal Drug Administration for the treatment of imatinib mesylate-resistant chronic myeloid leukemia. PROCEDURES: Dasatinib was tested against the Pe ... Full text Link to item Cite

Initial testing of cisplatin by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · May 2008 BACKGROUND: Cisplatin is one of the most widely used drugs for the treatment of solid tumors in adults and children. Here, we report the activity of cisplatin against the PPTP panels of childhood cancer xenografts. PROCEDURES: Cisplatin was evaluated again ... Full text Link to item Cite

Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · April 2008 BACKGROUND: Rapamycin is a highly specific inhibitor of mTOR, a serine/threonine kinase that controls cap-dependent translation. Here we report the activity of rapamycin against the in vitro and in vivo panels of the Pediatric Preclinical Testing Program ( ... Full text Link to item Cite

Initial testing of the VEGFR inhibitor AZD2171 by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · March 2008 BACKGROUND: Inhibition of vascular endothelial growth factor mediated signaling shows promise as an antiangiogenic strategy for solid tumors. AZD2171 is a potent and relatively selective inhibitor of the vascular endothelial growth factor (VEGF) receptor f ... Full text Link to item Cite

Initial testing (stage 1) of the proteasome inhibitor bortezomib by the pediatric preclinical testing program.

Journal Article Pediatr Blood Cancer · January 2008 BACKGROUND: Bortezomib is a proteasome inhibitor that has been approved by FDA for the treatment of multiple myeloma and that has completed phase 1 testing in children. The purpose of the current study was to evaluate the antitumor activity of bortezomib a ... Full text Link to item Cite

Stress and long-term survivors of brain cancer.

Journal Article Support Care Cancer · December 2007 INTRODUCTION: Adult brain tumor patients are joining the ranks of cancer survivors in increasing numbers in the United States. As a result, health care providers are faced with new challenges to address the need for psychosocial support in this population. ... Full text Link to item Cite

The pediatric preclinical testing program: description of models and early testing results.

Journal Article Pediatr Blood Cancer · December 2007 BACKGROUND: The Pediatric Preclinical Testing Program (PPTP) is an initiative supported by the National Cancer Institute (NCI) to identify novel therapeutic agents that may have significant activity against childhood cancers. The PPTP has established panel ... Full text Link to item Cite

Program preferences to reduce stress in caregivers of patients with brain tumors.

Journal Article Clin J Oncol Nurs · October 2007 Providing care for patients with cancer places caregivers at risk for experiencing elevated levels of stress. Caregivers of patients with brain tumors may be at increased risk because of the multifaceted needs of this patient population. As such, the autho ... Full text Link to item Cite

The combination of novel low molecular weight inhibitors of RAF (LBT613) and target of rapamycin (RAD001) decreases glioma proliferation and invasion.

Journal Article Mol Cancer Ther · September 2007 Monotherapies have proven largely ineffective for the treatment of glioblastomas, suggesting that increased patient benefit may be achieved by combining therapies. Two protumorigenic pathways known to be active in glioblastoma include RAS/RAF/mitogen-activ ... Full text Link to item Cite

Activity of VNP40101M (Cloretazine) in the treatment of CNS tumor xenografts in athymic mice.

Journal Article Neuro Oncol · July 2007 VNP40101M, or 1,2-bis(methylsulfonyl)-1-(2-choloroethyl)-2-(methylamino)carbonylhydrazine (Cloretazine), is a bifunctional prodrug that belongs to a class of DNA-modifying agents-the sulfonylhydrazines-that has been synthesized and been shown to have activ ... Full text Link to item Cite

A novel low-molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits glioma growth.

Journal Article Mol Carcinog · June 2007 Glioblastomas are highly lethal cancers that resist current therapies. Novel therapies under development target molecular mechanisms that promote glioblastoma growth. In glioblastoma patient specimens, the non-receptor tyrosine kinase focal adhesion kinase ... Full text Link to item Cite

Using the theory of planned behavior to understand the determinants of exercise intention in patients diagnosed with primary brain cancer.

Journal Article Psychooncology · March 2007 The purpose of the present study was to examine the demographic, medical, and social cognitive determinants of exercise intentions in a institution-based cohort of primary brain tumor patients. Using a cross-sectional survey, 100 primary brain tumor patien ... Full text Link to item Cite

Exercise interest and preferences among patients diagnosed with primary brain cancer.

Journal Article Support Care Cancer · January 2007 GOALS OF THE WORK: The purpose of the present investigation was to examine the interest and exercise preferences of an institution-based sample of brain tumor patients. Secondary aims were to examine potential differences in participant's interest and pref ... Full text Link to item Cite

Levels of stress and intervention preferences of caregivers of brain tumor patients.

Journal Article Cancer Nurs · 2007 The purpose of this pilot study was to assess the level of stress experienced by caregivers of brain tumor patients and to examine both their interest in and preferences for stress reduction programs. Using a convenience sample of 60 adult caregivers, we d ... Full text Link to item Cite

Stress and intervention preferences of patients with brain tumors.

Journal Article Support Care Cancer · December 2006 BACKGROUND: Despite advances in diagnosis, treatment, and management of brain tumors, a brain tumor (BT) can significantly disrupt a person's life and create stress. To design effective stress reduction interventions, it is essential to have an understandi ... Full text Link to item Cite

Differential levels of stress in caregivers of brain tumor patients--observations from a pilot study.

Journal Article Support Care Cancer · December 2006 OBJECTIVE: Caregivers of patients with brain tumors (BT) experience elevated levels of stress. Using pilot data, we sought to determine which caregivers are at risk for experiencing elevated levels of stress based on caregiver-demographic and patient-medic ... Full text Link to item Cite

AAL881, a novel small molecule inhibitor of RAF and vascular endothelial growth factor receptor activities, blocks the growth of malignant glioma.

Journal Article Cancer Res · September 1, 2006 Malignant gliomas are highly proliferative and angiogenic cancers resistant to conventional therapies. Although RAS and RAF mutations are uncommon in gliomas, RAS activity is increased in gliomas. Additionally, vascular endothelial growth factor and its co ... Full text Link to item Cite

Patterns of exercise across the cancer trajectory in brain tumor patients.

Journal Article Cancer · May 15, 2006 BACKGROUND: Exercise may represent a supportive intervention that may complement existing neurooncologic therapies and address a multitude of therapy-induced debilitating side effects in patients with brain tumors. Given the limited evidence, the authors c ... Full text Link to item Cite

ZD6474, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor, inhibits tumor growth of multiple nervous system tumors.

Journal Article Clin Cancer Res · November 15, 2005 PURPOSE: Primary central nervous system (CNS) tumors represent a diverse group of tumor types with heterogeneous molecular mechanisms that underlie their formation and maintenance. CNS tumors depend on angiogenesis and often display increased activity of E ... Full text Link to item Cite

Poly(ADP-ribose) polymerase-1 inhibition reverses temozolomide resistance in a DNA mismatch repair-deficient malignant glioma xenograft.

Journal Article Mol Cancer Ther · September 2005 Temozolomide is a DNA-methylating agent used in the treatment of malignant gliomas. In this study, we have examined if inhibition of poly(ADP-ribose) polymerase (PARP) could increase the cytotoxicity of temozolomide, particularly in cells deficient in DNA ... Full text Link to item Cite

Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamycin (RAD001) offers improved glioblastoma tumor growth inhibition.

Journal Article Mol Cancer Ther · January 2005 Malignant gliomas are highly lethal tumors that display striking genetic heterogeneity. Novel therapies that inhibit a single molecular target may slow tumor progression, but tumors are likely not dependent on a signal transduction pathway. Rather, maligna ... Link to item Cite

The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors.

Journal Article Cancer · May 1, 2003 Irinotecan is a water-soluble derivative of camptothecin, an alkylator originally extracted from the Chinese tree Camptotheca acuminata. Laboratory studies have demonstrated the activity of irinotecan in a broad panel of pediatric and adult central nervous ... Full text Link to item Cite

O6-benzylguanine-mediated enhancement of chemotherapy.

Journal Article Mol Cancer Ther · September 2002 We have previously demonstrated (A. E. Pegg, Cancer Res., 50: 6119-6129, 1990) that O6-benzylguanine (O6-BG) enhances nitrosourea, temozolomide, and cyclophosphamide activity in malignant glioma xenografts growing in athymic nude mice. More recently, we ha ... Link to item Cite

Activity of irofulven (6-hydroxymethylacylfulvene) in the treatment of glioblastoma multiforme-derived xenografts in athymic mice.

Journal Article Cancer Chemother Pharmacol · November 2001 PURPOSE: This study was conducted to define the activity of irofulven in the treatment of a series of xenografts derived from human glioblastoma multiforme growing subcutaneously and intracranially in athymic nude mice. METHODS: Athymic mice bearing subcut ... Full text Link to item Cite

Therapeutic activity of the topoisomerase I inhibitor J-107088 [6-N-(1-hydroxymethyla-2-hydroxyl) ethylamino-12,13-dihydro-13-(beta-D-glucopyranosyl) -5H-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7(6H)-dione]] against pediatric and adult central nervous system tumor xenografts.

Journal Article Cancer Chemother Pharmacol · September 2001 PURPOSE: The in vivo antitumor activity of a novel topoisomerase I inhibitor, J-107088, was tested in athymic nude mice bearing subcutaneous or intracranial pediatric and adult malignant CNS tumor-derived xenografts. METHODS: J-107088 was administered to a ... Full text Link to item Cite

Acyl derivatives of demethylpenclomedine, an antitumor-active, non-neurotoxic metabolites of penclomedine.

Journal Article Cancer Chemother Pharmacol · July 2001 PURPOSE: The purpose of this investigation was to compare the antitumor activities of a series of acyl derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma metabolite of penclomedine (PEN) observed to be an active antitumor agent in vivo and no ... Full text Link to item Cite

Therapeutic activity of 7-[(2-trimethylsilyl)ethyl)]-20 (S)-camptothecin against central nervous system tumor-derived xenografts in athymic mice.

Journal Article Cancer Chemother Pharmacol · July 2001 PURPOSE: Camptothecins have emerged as an important new class of antitumor drugs. Camptothecin derivatives such as CPT-11 and topotecan are commercially available and approved for the treatment of colorectal (CPT-11) and ovarian and small-cell lung cancer ... Full text Link to item Cite

Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft.

Journal Article Clin Cancer Res · October 2000 Temozolomide, an imidazole tetrazinone, and CPT-11, a camptothecin derivative, have previously been shown to have anti-central nervous system tumor activity in laboratory and clinical studies. The current experiments were designed to evaluate the activity ... Link to item Cite

O6-benzylguanine-mediated enhancement of nitrosourea activity in Mer- central nervous system tumor xenografts--implications for clinical trials.

Journal Article Cancer Chemother Pharmacol · 2000 PURPOSE: To evaluate the role of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) plus O6-benzylguanine (O6-BG) in the treatment of both Mer+ and Mer- tumors. METHODS: The effect of pretreatment with O6-BG on the activity of BCNU against Mer- human central nerv ... Full text Link to item Cite

Schedule-dependent activity of irinotecan plus BCNU against malignant glioma xenografts.

Journal Article Cancer Chemother Pharmacol · 2000 PURPOSE: To further evaluate the activity of irinotecan (CPT-11) plus 1,3-bis-(chloroethyl)-1-nitrosourea (BCNU) in the treatment of central nervous system tumor-derived xenografts in athymic nude mice. METHODS: We report studies evaluating the schedule-de ... Full text Link to item Cite

O6-benzylguanine-mediated enhancement of nitrosourea activity in Mer- central nervous system tumor xenografts - Implications for clinical trials

Journal Article Cancer Chemotherapy and Pharmacology · 2000 Purpose: To evaluate the role of 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) plus O6-benzylguanine (O6-BG) in the treatment of both Mer+ and Mer- tumors. Methods: The effect of pretreatment with O6-BG on the activity of BCNU against Mer- human central nerv ... Cite

Modulation of cyclophosphamide activity by O6-alkylguanine-DNA alkyltransferase.

Journal Article Cancer Chemother Pharmacol · 1999 PURPOSE: The human medulloblastoma cell line D283 Med (4-HCR), a line resistant to 4-hydroperoxycyclophosphamide (4-HC), displays enhanced repair of DNA interstrand crosslinks induced by phosphoramide mustard. D283 Med (4-HCR) cells are cross-resistant to ... Full text Link to item Cite

Therapeutic efficacy of vinorelbine against pediatric and adult central nervous system tumors.

Journal Article Cancer Chemother Pharmacol · 1998 PURPOSE: The activity of vinorellbine, a new semisynthetic vinca alkaloid, was evaluated against a battery of human tumor xenografts derived from adult and pediatric CNS malignancies. METHODS: Tumors included adult high-grade gliomas (D-54 MG, D-245 MG), c ... Full text Link to item Cite

Enhancement of irinotecan (CPT-11) activity against central nervous system tumor xenografts by alkylating agents.

Journal Article Cancer Chemother Pharmacol · 1998 Two major obstacles in the treatment of patients with central nervous system malignancies are drug resistance and host toxicity. The goal of combination chemotherapy is to achieve therapeutic effects that are more favorable than using a single drug alone, ... Full text Link to item Cite

Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft.

Journal Article Cancer Res · July 15, 1997 A methylator-resistant human glioblastoma multiforme xenograft, D-245 MG (PR), in athymic nude mice was established by serially treating the parent xenograft D-245 MG with procarbazine. D-245 MG xenografts were sensitive to procarbazine, temozolomide, N-me ... Link to item Cite

Therapeutic efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothecin against pediatric and adult central nervous system tumor xenografts.

Journal Article Cancer Chemother Pharmacol · 1997 Therapy of patients with malignant central nervous system tumors is frequently unsuccessful, reflecting limitations of current surgical, radiotherapeutic, and pharmacotherapeutic treatments. The camptothecin derivative irinotecan (CPT-11) has been shown to ... Full text Link to item Cite

Characterization of the mechanisms of busulfan resistance in a human glioblastoma multiforme xenograft.

Journal Article Cancer Chemother Pharmacol · 1997 Busulfan is an alkylating agent commonly used in the treatment of chronic myelogenous leukemia and in combination with cyclophosphamide in preparation for allogeneic bone marrow transplantation. Serial treatment of a childhood high-grade glioma xenograft ( ... Full text Link to item Cite

Evaluation of meta-[211At]astatobenzylguanidine in an athymic mouse human neuroblastoma xenograft model.

Journal Article Nucl Med Biol · August 1996 A paired-label biodistribution was performed in athymic mice bearing SK-N-SH human neuroblastoma xenografts to compare the tissue uptake of meta-[211At]astatobenzylguanidine ([211At]MABG) and [131I]MIBG. Significantly higher (p < 0.05) uptake of [211At]MAB ... Full text Link to item Cite

Localisation of [131I]MIBG in nude mice bearing SK-N-SH human neuroblastoma xenografts: effect of specific activity.

Journal Article Br J Cancer · May 1996 The biodistribution of no-carrier-added (n.c.a.) meta-[131I]iodobenzylguanidine ([131I]MIBG) and that prepared by the standard isotopic exchange method were compared in athymic mice bearing SK-N-SH human neuroblastoma xenografts. No advantage in tumour upt ... Full text Open Access Link to item Cite

Enhancement of melphalan activity by inhibition of DNA polymerase-alpha and DNA polymerase-beta.

Journal Article Cancer Chemother Pharmacol · 1996 Our previous studies exploring melphalan resistance in the human rhabdomyosarcoma xenograft TE-671 MR revealed elevation of DNA polymerase-alpha and DNA polymerase-beta. The present study evaluated the alteration of melphalan activity in TE-671 (melphalan- ... Full text Link to item Cite

Activity of temozolomide in the treatment of central nervous system tumor xenografts.

Journal Article Cancer Res · July 1, 1995 The activity of 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin- 4(3H)-one (temozolomide) in the treatment of a panel of xenografts derived from ependymoma, medulloblastoma, and childhood and adult high-grade glioma was evaluated in athymic nude mice b ... Link to item Cite

Busulfan therapy of central nervous system xenografts in athymic mice.

Journal Article Cancer Chemother Pharmacol · 1994 We evaluated the antitumor activity of busulfan against a panel of tumor cell lines and xenografts in athymic nude mice derived from childhood high-grade glioma, adult high-grade glioma, ependymoma, and medulloblastoma. Busulfan displayed similar activity ... Full text Link to item Cite

Activity of 9-dimethylaminomethyl-10-hydroxycamptothecin against pediatric and adult central nervous system tumor xenografts.

Journal Article Cancer Chemother Pharmacol · 1994 The activity of dimethylaminomethyl-10-hydroxycamptothecin (topotecan) was evaluated against a panel of xenografts derived from ependymomas (D528 EP, D612 EP), childhood high-grade gliomas (D-456 MG, D-212 MG), adult high-grade gliomas (D-245 MG, D-54 MG), ... Full text Link to item Cite