Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiationRole of oxygenation, angiopoietin-1, and matrix metalloproteinases

✓ The role of matrix metalloproteinases (MMP's) and their inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), in human brain tumor invasion was investigated. Gelatinolytic activity was assayed via gelatin zymography, and four MMP's (MMP-1, MMP-2, MMP-3, and MMP-9) and TIMP-1 were immunolocalized in human brain tumors and in normal brain tissues using monoclonal antibodies. The tissue was surgically removed from 44 patients: glioblastoma (five cases), anaplastic astrocytoma (six cases), astrocytoma (four cases), metastatic tumor (six cases), neurinoma (10 cases), meningioma (10 cases), and normal brain tissue (three cases). Glioblastomas, anaplastic astrocytomas, and metastatic tumors showed high gelatinolytic activity and positive immunostaining for MMP's; TIMP-1 was also expressed in these tumors, but some tumor cells were negative for the antibody. Astrocytomas had low gelatinolytic activity and the tumor cells showed no immunoreactivity for MMP's and TIMP-1. Although neurinomas and meningiomas had only moderate proteinase activity and exhibited positive immunoreactivity for MMP-9, intense expression of TIMP-1 was simultaneously observed in these tumor cells. These findings suggest that MMP's play an important role in human brain tumor invasion, probably due to an imbalance between the production of MMP's and TIMP-1 by the tumor cells.

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Kinetics of Antitumor Immunity in Experimental Brain Tumor

Neurologia medico-chirurgica ◽

10.2176/nmc.22.689 ◽

1982 ◽

Vol 22 (9) ◽

pp. 689-695

Author(s):

Toshimitsu AIDA ◽

Hiroshi ABE ◽

Sadao KANEKO ◽

Mitsuo TSURU ◽

Takao KODAMA ◽

...

Keyword(s):

Brain Tumor ◽

Antitumor Immunity ◽

Experimental Brain Tumor ◽

Kinetics Of

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Brain Tumor: Response to Radiation

Radiology ◽

10.1148/6.1.66 ◽

1926 ◽

Vol 6 (1) ◽

pp. 66-67 ◽

Cited By ~ 1

Author(s):

John S. Derr

Keyword(s):

Brain Tumor ◽

Tumor Response

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Brain tumor response to nimotuzumab treatment evaluated on magnetic resonance imaging

Pediatrics International ◽

10.1111/ped.12212 ◽

2014 ◽

Vol 56 (1) ◽

pp. 43-46 ◽

Cited By ~ 3

Author(s):

Evelio Rafael González Dalmau ◽

Carlos Cabal Mirabal ◽

Giselle Saurez Martínez ◽

Agustín Lage Dávila ◽

José Carlos Ugarte Suárez ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Brain Tumor ◽

Magnetic Resonance ◽

Tumor Response ◽

Resonance Imaging

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AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, in combination with chemotherapy in adult patients with advanced solid tumors

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14033 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14033-14033 ◽

Cited By ~ 6

Author(s):

A. C. Mita ◽

D. Wang ◽

C. H. Takimoto ◽

E. Malseed ◽

L. Nguyen ◽

...

Keyword(s):

Bladder Cancer ◽

Antitumor Activity ◽

Solid Tumors ◽

Neutralizing Antibodies ◽

Tumor Response ◽

Adult Patients ◽

Advanced Solid Tumors ◽

Open Label ◽

Amg 386 ◽

Angiopoietin 1

14033 Introduction: AMG 386 is a selective angiopoietin 1 /2-neutralizing peptibody that inhibits angiogenesis by preventing interaction between angiopoietins and Tie2 receptors. This open-label study evaluated the safety, pharmacokinetics (PK), and antitumor activity of AMG 386 in combination with FOLFOX-4 (F), carboplatin + paclitaxel (CP), or docetaxel (D) in adult patients (pts) with advanced solid tumors. Methods: Three cohorts of 6–9 pts received 1 full cycle of chemotherapy (2 weeks of F or 3 weeks of D 75 mg/m2 or CP). Administration of AMG 386 10 mg/kg IV weekly was started on day 1 of cycle 2 for patients who did not experience a dose-limiting toxicity (DLT) to chemotherapy during cycle 1, and continued until disease progression or intolerance. Safety and tolerability, tumor response (RECIST every 8 weeks), PK profiles of AMG 386 and chemotherapy agents, and formation of antibodies to AMG 386 were assessed. Results: As of October 2, 2006, 16 pts have received AMG 386: 6 pts in the F cohort, 5 in CP, and 5 in D; 7 pts were men, median age 59.5 years (range, 44- 75 years). No AMG 386-related serious AEs or DLTs were reported. AEs related to chemotherapy + AMG 386 in = 2 pts were neutropenia (n = 3), thrombocytopenia (n=2), diarrhea (n=2), and vomiting (n=2). No neutralizing antibodies were observed. F, CP, and D coadministered with AMG 386 did not appear to affect the PK profile of AMG 386, and AMG 386 had no apparent effect on the PK profile of 5 FU, leucovorin, C, P, or D. Tumor response data are available for 6 pts. One pt receiving CP+ AMG 386 for bladder cancer refractory to gemcitabine/cisplatin had a complete response (CR) at week 8, confirmed at week 16. Stable disease in 4 pts and progressive disease in 1 pt were also observed. Conclusions: Weekly administration of AMG 386 in combination with F, CP, or D appears to be safe and well tolerated. A CR in bladder cancer suggests promising antitumor activity of AMG 386 in combination with chemotherapy. Further clinical studies of AMG 386 in combination with chemotherapy and other targeted agents are warranted. [Table: see text]

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