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Article ; Online: Hsp90 inhibition enhances PI-3 kinase inhibition and radiosensitivity in glioblastoma.

Wachsberger, Phyllis R / Lawrence, Yaacov Richard / Liu, Yi / Rice, Barbara / Feo, Nicholas / Leiby, Benjamin / Dicker, Adam P

Journal of cancer research and clinical oncology

2014 Volume 140, Issue 4, Page(s) 573–582

Abstract: Purpose: Combined targeting with a PI3-kinase inhibitor, BKM120, and an Hsp90 inhibitor, HSP990, was investigated as a multi-targeted approach to potentiate cell death in glioblastoma (GBM). Additionally, the effect of dual drug treatment combined with ... ...

Abstract	Purpose: Combined targeting with a PI3-kinase inhibitor, BKM120, and an Hsp90 inhibitor, HSP990, was investigated as a multi-targeted approach to potentiate cell death in glioblastoma (GBM). Additionally, the effect of dual drug treatment combined with cytotoxic stress (radiation therapy) was examined. Methods: Four human GBM cell lines containing wild-type or mutated PTEN and/or p53 were studied. The effects of drug treatments on cell viability, apoptosis induction, pAKt activity, cell cycle arrest, clonogenicity, and tumor growth delay were studied. Results: Combined concurrent treatment with both drugs produced more cell killing in cell viability and apoptosis assays than either drug alone. BKM120 plus HSP990 induced suppression of baseline Akt signaling as well as radiation (RT)-induced pAkt signaling in all cell lines. Cell cycle analysis revealed that HSP990 and BKM120, singly or combined, induced G2/M arrest leading to apoptosis/necrosis and polyploidy. Additionally, the drugs radiosensitized GBM cells in clonogenic assays. In vivo tumor growth delay studies demonstrated the effectiveness of combined drug treatment with HSP990 and BKM120 over single drug treatment, as well as the effectiveness of combined drug treatment in enhancing the effectiveness of radiation therapy. Conclusions: In conclusion, HSP990 and BKM120, with and without RT, are active agents against glioma tumors. The sensitivity to these agents does not appear to depend on PTEN/p53status in the cell lines tested. We suggest that the combined action of both drugs is a viable multi-targeted strategy with the potential to improve clinical outcome for patients with high-grade glioma.
MeSH term(s)	Aminopyridines/pharmacology ; Animals ; Apoptosis/drug effects ; Blotting, Western ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Brain Neoplasms/radiotherapy ; Cell Proliferation/drug effects ; Flow Cytometry ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/radiation effects ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Glioblastoma/radiotherapy ; HSP90 Heat-Shock Proteins/antagonists & inhibitors ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Mice ; Mice, Nude ; Morpholines/pharmacology ; Phosphatidylinositol 3-Kinase/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Radiation Tolerance/drug effects ; Radiation-Sensitizing Agents/pharmacology ; Tumor Cells, Cultured
Chemical Substances	Aminopyridines ; HSP90 Heat-Shock Proteins ; Morpholines ; NVP-BKM120 ; Phosphoinositide-3 Kinase Inhibitors ; Radiation-Sensitizing Agents ; Phosphatidylinositol 3-Kinase (EC 2.7.1.137)
Language	English
Publishing date	2014-02-06
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-014-1594-6
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Article ; Online: Cediranib enhances control of wild type EGFR and EGFRvIII-expressing gliomas through potentiating temozolomide, but not through radiosensitization: implications for the clinic.

Wachsberger, Phyllis R / Lawrence, Richard Yaacov / Liu, Yi / Xia, Xu / Andersen, Barbara / Dicker, Adam P

Journal of neuro-oncology

2011 Volume 105, Issue 2, Page(s) 181–190

Abstract: Glioblastomas (GBM) frequently overexpress the epidermal growth factor receptor (wtEGFR) or its mutant, EGFRvIII, contributing to chemo- and radioresistance. The current standard of care is surgery followed by radiation therapy with concurrent ... ...

Abstract	Glioblastomas (GBM) frequently overexpress the epidermal growth factor receptor (wtEGFR) or its mutant, EGFRvIII, contributing to chemo- and radioresistance. The current standard of care is surgery followed by radiation therapy with concurrent temozolomide (TMZ) followed by adjuvant TMZ. New treatment strategies for GBM include blockade of EGFR signaling and angiogenesis. Cediranib is a highly potent receptor tyrosine kinase inhibitor that inhibits all three VEGF receptors. This study investigated the radiosensitizing potential of cediranib in combination with TMZ in U87 GBM xenografts expressing wtEGFR or EGFRvIII. U87 GBM cells stably transfected with either wtEGFR or EGFRvIII were injected into the hind limbs of nude mice. Cediranib was dosed at 3 mg/kg daily five times a week orally for 2 weeks. TMZ was dosed at 10 mg/kg once only on day 0. Radiotherapy (RT) consisted of 3 fractions of 5 Gy (days 0-2). Cediranib did not radiosensitize either tumor type; however, cediranib did enhance the effectiveness of TMZ in both transfectants. Our results suggest that combining cediranib with temozolomide in the clinic will lead to improved tumor control.
MeSH term(s)	Animals ; Antineoplastic Agents, Alkylating/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Brain Neoplasms/drug therapy ; Brain Neoplasms/metabolism ; Brain Neoplasms/radiotherapy ; Cell Survival/drug effects ; Cell Survival/radiation effects ; Dacarbazine/analogs & derivatives ; Dacarbazine/therapeutic use ; ErbB Receptors/metabolism ; Glioma/drug therapy ; Glioma/metabolism ; Glioma/radiotherapy ; Humans ; Immunoblotting ; Mice ; Mice, Nude ; Quinazolines/therapeutic use ; Radiation Tolerance/drug effects ; Temozolomide ; Tumor Cells, Cultured ; Tumor Stem Cell Assay ; Vascular Endothelial Growth Factor A/metabolism ; X-Rays
Chemical Substances	Antineoplastic Agents, Alkylating ; Quinazolines ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; epidermal growth factor receptor VIII ; Dacarbazine (7GR28W0FJI) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; cediranib (NQU9IPY4K9) ; Temozolomide (YF1K15M17Y)
Language	English
Publishing date	2011-04-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604875-4
ISSN	1573-7373 ; 0167-594X
ISSN (online)	1573-7373
ISSN	0167-594X
DOI	10.1007/s11060-011-0580-y
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Article ; Online: Epidermal growth factor receptor expression modulates antitumor efficacy of vandetanib or cediranib combined with radiotherapy in human glioblastoma xenografts.

Wachsberger, Phyllis R / Lawrence, Yaacov R / Liu, Yi / Daroczi, Borbala / Xu, Xia / Dicker, Adam P

International journal of radiation oncology, biology, physics

2010 Volume 82, Issue 1, Page(s) 483–491

Abstract: Purpose: The purpose of this study was to determine the ability of radiation therapy (RT) combined with the tyrosine kinase inhibitors (TKI) vandetanib (antiepidermal growth factor receptor [EGFR] plus antivascular endothelial growth factor receptor [ ... ...

Abstract	Purpose: The purpose of this study was to determine the ability of radiation therapy (RT) combined with the tyrosine kinase inhibitors (TKI) vandetanib (antiepidermal growth factor receptor [EGFR] plus antivascular endothelial growth factor receptor [anti-VEGFR]) and cediranib (anti-VEGFR) to inhibit glioblastoma multiforme (GBM) growth. A secondary aim was to investigate how this regimen is modulated by tumor EGFR expression. Methods and materials: Radiosensitivity was assessed by clonogenic cell survival assay. VEGF secretion was quantified by enzyme-linked immunosorbent assay. GBM (U87MG wild-type EGFR [wtEGFR] and U87MG EGFR-null) xenografts were treated with vandetanib, cediranib, and RT, alone or in combinations. Excised tumor sections were stained for proliferative and survival biomarkers. Results: In vitro, U87MG wtEGFR and U87 EGFR-null cells had similar growth kinetics. Neither TKI affected clonogenic cell survival following RT. However, in vivo, exogenous overexpression of wtEGFR decreased tumor doubling time (T2x) in U87MG xenografts (2.70 vs. 4.41 days for U87MG wtEGFR vs. U87MG vector, respectively). In U87MG EGFR-null cells, TKI combined with radiation was no better than radiation therapy alone. In U87MG wtEGFR, RT in combination with vandetanib (but not with cediranib) significantly increased tumor T2x compared with RT alone (T2x, 10.4 days vs. 4.8 days; p < 0.001). In vivo, growth delay correlated with suppression of pAkt, survivin, and Ki67 expression in tumor samples. The presence of EGFR augmented RT-stimulated VEGF release; this effect was inhibited by vandetanib. Conclusions: EGFR expression promoted tumor growth in vivo but not in vitro, suggesting a microenvironmental effect. GBM xenografts expressing EGFR exhibited greater sensitivity to both cediranib and vandetanib than EGFR-null tumors. Hence EGFR status plays a major role in determining a tumor's in vivo response to radiation combined with TKI, supporting a "personalized" approach to GBM management.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Chemoradiotherapy/methods ; Drug Administration Schedule ; ErbB Receptors/metabolism ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Glioblastoma/therapy ; Humans ; Mice ; Mice, Nude ; Neoplasm Proteins/metabolism ; Piperidines/therapeutic use ; Quinazolines/therapeutic use ; Radiation Tolerance ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors ; Tumor Burden ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor ; Neoplasm Proteins ; Piperidines ; Quinazolines ; ErbB Receptors (EC 2.7.10.1) ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1) ; cediranib (NQU9IPY4K9) ; vandetanib (YO460OQ37K)
Language	English
Publishing date	2010-11-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2010.09.019
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Article: Quercetin selectively inhibits bioreduction and enhances apoptosis in melanoma cells that overexpress tyrosinase.

Thangasamy, Thilakavathy / Sittadjody, Sivanandane / Lanza-Jacoby, Susan / Wachsberger, Phyllis R / Limesand, Kirsten H / Burd, Randy

Nutrition and cancer

2007 Volume 59, Issue 2, Page(s) 258–268

Abstract: Tyrosinase is expressed in melanoma cells and catalyzes the formation of 3,3',4',5,7-pentahydroxyflavone (quercetin) into reactive quinone species and subsequent glutathionyl adducts. Therefore, we examined the effect of quercetin metabolism on the ... ...

Abstract	Tyrosinase is expressed in melanoma cells and catalyzes the formation of 3,3',4',5,7-pentahydroxyflavone (quercetin) into reactive quinone species and subsequent glutathionyl adducts. Therefore, we examined the effect of quercetin metabolism on the glutathione (GSH) bioreduction pathway and cell viability in DB-1 melanoma cells that express varying levels of tyrosinase (Tyr+). In a cell-free system, GSH was significantly decreased by quercetin, which coincided with the formation of glutathionyl adducts. In Tyr+ clones, quercetin decreased bioreduction capacity and increased reactive oxygen species (ROS) to a greater degree compared to control cells. The antioxidant/electrophile response element-induced enzymes, glutathione-S-transferase (GST), and nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1 were expressed at high levels in Tyr+ cells and contributed to pro-oxidant quercetin metabolism. The basal level of ROS and apoptosis was higher in Tyr+ cells and were selectively increased after exposure to quercetin. The increase in apoptosis following quercetin exposure was p53/Bax mediated and correlated with a decrease in GST-driven bioreduction capacity and an increase in ROS. In conclusion, quercetin can selectively sensitize Tyr+ expressing melanoma cells to apoptosis and may serve as an adjuvant to chemotherapy by enhancing cell death and interfering with GST-mediated drug resistance.
MeSH term(s)	Apoptosis/drug effects ; Cell Line, Tumor ; Cell Survival ; Dose-Response Relationship, Drug ; Enzyme Activation/drug effects ; Gene Expression Regulation, Enzymologic/drug effects ; Glutathione/metabolism ; Humans ; Melanocytes/drug effects ; Melanocytes/enzymology ; Melanoma/enzymology ; Monophenol Monooxygenase/metabolism ; Quercetin/pharmacology ; Reactive Oxygen Species/metabolism
Chemical Substances	Reactive Oxygen Species ; Quercetin (9IKM0I5T1E) ; Monophenol Monooxygenase (EC 1.14.18.1) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2007
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424433-3
ISSN	0163-5581
ISSN	0163-5581
DOI	10.1080/01635580701499545
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Article: VEGF trap in combination with radiotherapy improves tumor control in u87 glioblastoma.

Wachsberger, Phyllis R / Burd, Randy / Cardi, Chris / Thakur, Mathew / Daskalakis, Constantine / Holash, Jocelyn / Yancopoulos, George D / Dicker, Adam P

International journal of radiation oncology, biology, physics

2007 Volume 67, Issue 5, Page(s) 1526–1537

Abstract: Purpose: To determine the effect of vascular endothelial growth factor VEGF Trap (Regeneron Pharmaceuticals, Tarrytown, NY), a humanized soluble vascular endothelial growth factor (VEGF) receptor protein, and radiation (RT) on tumor growth in U87 ... ...

Abstract	Purpose: To determine the effect of vascular endothelial growth factor VEGF Trap (Regeneron Pharmaceuticals, Tarrytown, NY), a humanized soluble vascular endothelial growth factor (VEGF) receptor protein, and radiation (RT) on tumor growth in U87 glioblastoma xenografts in nude mice. Methods and materials: U87 cell suspensions were implanted subcutaneously into hind limbs of nude mice. VEGF Trap (2.5-25 mg/kg) was administered every 3 days for 3 weeks alone or in combination with a single dose of 10 Gy or fractionated RT (3 x 5 Gy). In addition, three scheduling protocols for VEGF Trap plus fractionated RT were examined. Results: Improved tumor control was seen when RT (either single dose or fractionated doses) was combined with the lowest dose of VEGF Trap (2.5 mg/kg). Scheduling did not significantly affect the efficacy of combined therapy. Although high-dose VEGF Trap (10 mg/kg or 25 mg/kg) significantly reduced tumor growth over that of RT alone, there was no additional benefit to combining high-dose VEGF Trap with RT. Conclusions: Vascular endothelial growth factor Trap plus radiation is clearly better than radiation alone in a U87 subcutaneous xenograft model. Although high doses of VEGF Trap alone are highly efficacious, it is unclear whether such high doses can be used clinically without incurring normal tissue toxicities. Thus, information on lower doses of VEGF Trap and ionizing radiation is of clinical relevance.
MeSH term(s)	Angiogenesis Inhibitors/administration & dosage ; Animals ; Combined Modality Therapy ; Drug Screening Assays, Antitumor ; Fluorodeoxyglucose F18 ; Glioblastoma/blood supply ; Glioblastoma/drug therapy ; Glioblastoma/metabolism ; Glioblastoma/radiotherapy ; Mice ; Mice, Nude ; Microcirculation/drug effects ; Microcirculation/radiation effects ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/metabolism ; Radiation Tolerance/drug effects ; Radiopharmaceuticals ; Radiotherapy Dosage ; Recombinant Fusion Proteins/administration & dosage ; Transplantation, Heterologous ; Vascular Endothelial Growth Factors/antagonists & inhibitors ; Vascular Endothelial Growth Factors/metabolism
Chemical Substances	Angiogenesis Inhibitors ; Neoplasm Proteins ; Radiopharmaceuticals ; Recombinant Fusion Proteins ; Vascular Endothelial Growth Factors ; Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2007-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2006.11.011
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Article: Effect of the tumor vascular-damaging agent, ZD6126, on the radioresponse of U87 glioblastoma.

Wachsberger, Phyllis R / Burd, Randy / Marero, Nichol / Daskalakis, Constantine / Ryan, Anderson / McCue, Peter / Dicker, Adam P

Clinical cancer research : an official journal of the American Association for Cancer Research

2005 Volume 11, Issue 2 Pt 1, Page(s) 835–842

Abstract: Purpose: The effect of ZD6126 on tumor oxygen tension and tumor growth delay in combination with ionizing radiation was examined in the human U87 glioblastoma tumor model. Resistance to ZD6126 treatment was investigated with the nitric oxide synthase ... ...

Abstract	Purpose: The effect of ZD6126 on tumor oxygen tension and tumor growth delay in combination with ionizing radiation was examined in the human U87 glioblastoma tumor model. Resistance to ZD6126 treatment was investigated with the nitric oxide synthase inhibitor, l-N(G)-nitroarginine methyl ester (hydrochloride; l-NAME/active form, l-NNA). Methods: U87 human xenografts were grown in athymic nude mice. ZD6126 was given with or without l-NNA. Tumor oxygen tension was measured using the Oxford Oxylite (Oxford, England) fiberoptic probe system. Tumor volume was determined by direct measurement with calipers and calculated by the formula [(smallest diameter(2) x widest diameter)/2]. Results: Multiple doses of ZD6126 treatment (three doses) had a significant effect on tumor growth delay, reducing the average daily tumor growth rate from 29% to 16%. When given 1 hour before radiation, ZD6126 caused an acute increase in hypoxia in U87 tumors, and reduced tumor growth delay compared with that of radiation alone. The combination of ZD6126 given after radiation, either as a single dose or in multiple doses, had greater or similar antitumor activity compared with radiation alone. Twenty-four hours after administration, a single dose of ZD6126 induced little (10 +/- 8%) necrosis in U87 xenografts. l-NNA, when given in combination with ZD6126, significantly enhanced the effectiveness of ZD6126 in inducing tumor necrosis. Conclusions: Our observation that ZD6126-induced tumor hypoxia can decrease radiation response when ZD6126 is given prior to radiation indicates the importance of scheduling. Our findings suggest that the optimal therapeutic benefit of ZD6126 plus radiation in human glioblastoma may require multiple dosing in combination with a nitric oxide synthase inhibitor, to be scheduled following radiotherapy.
MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Animals ; Blood Vessels/metabolism ; Blood Vessels/pathology ; Brain Neoplasms/blood supply ; Brain Neoplasms/therapy ; Combined Modality Therapy ; Drug Therapy, Combination ; Enzyme Inhibitors/pharmacology ; Glioblastoma/blood supply ; Glioblastoma/therapy ; Humans ; Hypoxia ; Mice ; Mice, Nude ; Necrosis ; Neovascularization, Pathologic/therapy ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitroarginine/pharmacology ; Organophosphorus Compounds/therapeutic use ; Oxygen/metabolism ; Radiation Tolerance ; Radiation, Ionizing ; Transplantation, Heterologous ; Tumor Cells, Cultured ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Angiogenesis Inhibitors ; Enzyme Inhibitors ; N-acetylcochinol-O-phosphate ; Organophosphorus Compounds ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Nitroarginine (2149-70-4) ; Nitric Oxide (31C4KY9ESH) ; Nitric Oxide Synthase (EC 1.14.13.39) ; Oxygen (S88TT14065)
Language	English
Publishing date	2005-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
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Article: Tumor oxygenation and acidification are increased in melanoma xenografts after exposure to hyperglycemia and meta-iodo-benzylguanidine.

Burd, Randy / Lavorgna, Stephanie N / Daskalakis, Constantine / Wachsberger, Phyllis R / Wahl, Miriam L / Biaglow, John E / Stevens, Craig W / Leeper, Dennis B

Radiation research

2003 Volume 159, Issue 3, Page(s) 328–335

Abstract: Tumor oxygen tension and extracellular pH (pH(e)) are physiological parameters that can be manipulated to improve current cancer therapies. Many human tumors consist of cells that are chronically exposed to low pH(e). Exposure of tumor cells in culture ... ...

Abstract	Tumor oxygen tension and extracellular pH (pH(e)) are physiological parameters that can be manipulated to improve current cancer therapies. Many human tumors consist of cells that are chronically exposed to low pH(e). Exposure of tumor cells in culture to glucose decreases oxygen consumption (oxygen sparing or Crabtree effect), and while this effect is absent in low pH-adapted tumor cells, it can be restored by combining the respiratory inhibitor meta-iodo-benzylguanidine (MIBG) with glucose (Burd et al., Cancer Res. 61, 5630-5635, 2001). The effects of hyperglycemia and MIBG on tumor oxygen tension and on pH(e) were investigated in human melanoma xenografts in SCID mice. An oral gavage of 1 M glucose (2 g/kg) increased the average blood glucose concentration from <140 mg/dl to approximately 400 mg/dl. Although tumor pH(e) decreased from pH 6.7 to pH 6.5 (P < 0.01) after about 60 min, no change in tumor oxygen tension was observed. However, when oral glucose and MIBG (15 mg/kg) were administered together, oxygen tension increased from 2.8 mmHg to approximately 17 mmHg, and tumor pH(e) decreased from pH 6.7 to pH 6.3 (P < 0.01) after about 115 min. In conclusion, administration of glucose together with MIBG increases tumor oxygen tension and also increases the magnitude and duration of acidification. Hyperglycemia plus MIBG has the potential to improve response to radiation therapy as well as to hyperthermia and some chemotherapies.
MeSH term(s)	Animals ; Blood Glucose/metabolism ; Glucose/pharmacology ; Guanidines/pharmacology ; Humans ; Hydrogen-Ion Concentration ; Hyperglycemia/metabolism ; Hyperglycemia/pathology ; Melanoma/metabolism ; Melanoma/pathology ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Neoplasms/metabolism ; Oxygen/metabolism ; Time Factors
Chemical Substances	Blood Glucose ; Guanidines ; benzylguanidine (2211-57-6) ; Glucose (IY9XDZ35W2) ; Oxygen (S88TT14065)
Language	English
Publishing date	2003-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80322-4
ISSN	1938-5404 ; 0033-7587
ISSN (online)	1938-5404
ISSN	0033-7587
DOI	10.1667/0033-7587(2003)159[0328:toaaai]2.0.co;2
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Article ; Online: Hsp90 inhibition enhances PI-3 kinase inhibition and radiosensitivity in glioblastoma.

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Article ; Online: Cediranib enhances control of wild type EGFR and EGFRvIII-expressing gliomas through potentiating temozolomide, but not through radiosensitization: implications for the clinic.

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Article ; Online: Epidermal growth factor receptor expression modulates antitumor efficacy of vandetanib or cediranib combined with radiotherapy in human glioblastoma xenografts.

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Article: Quercetin selectively inhibits bioreduction and enhances apoptosis in melanoma cells that overexpress tyrosinase.

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Article: VEGF trap in combination with radiotherapy improves tumor control in u87 glioblastoma.

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Article: Effect of the tumor vascular-damaging agent, ZD6126, on the radioresponse of U87 glioblastoma.

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Article: Tumor oxygenation and acidification are increased in melanoma xenografts after exposure to hyperglycemia and meta-iodo-benzylguanidine.

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