Radiochemotherapy of Malignant Glioma in Adults

Kortmann, Rolf‐Dieter; Jeremić, Branislav; Weller, Michael; Plaßwilm, Ludwig; Bamberg, M.

doi:10.1007/s00066-003-1027-y

Cited by 62 publications

(37 citation statements)

References 119 publications

(102 reference statements)

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“…These facts stress the need for more effective therapeutic strategies. 2 Rapid cell proliferation and high invasive capacity of glioma cells are crucial for tumor development and progression. Moreover, induction of angiogenesis is an essential prerequisite for tumor growth and spread, and precedes malignant tumor formation.…”

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confidence: 99%

Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro

Parthymou

Kardamakis

Pavlopoulos

et al. 2004

Intl Journal of Cancer

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Malignant gliomas are angiogenesis dependent and present a remarkable degree of resistance to radiotherapy. In the present work, we studied the effect of irradiation of C6 glioma cells on their proliferation and activation in vitro and on glioma cell-induced angiogenesis in vivo and in vitro. Irradiation of C6 glioma cells decreased cell proliferation in a dosedependent manner. Interestingly, metalloproteinase-2 and -9 expression and secretion, as well as integrin ␣ v expression, increased with elevated doses of X rays 48 hr after irradiation and was mostly evident at the higher doses used. When pre-irradiated C6 cells were implanted on nonirradiated chicken embryo chorioallantoic membranes (CAMs), there was a significant dose-dependent increase in tumor induced angiogenesis, compared to angiogenesis induced by nonirradiated cells. Similar results were obtained when C6 cells were irradiated 48 hr after their inocculation onto nonirradiated CAMs. In the same line, conditioned medium from irradiated C6 cells significantly increased endothelial cell proliferation and migration in vitro, in a manner dependent on the dose of X rays. These results explain at least in part the low effectiveness of radiation therapy of malignant gliomas and support the notion that inhibition of angiogenesis in parallel with radiotherapy may represent a new therapeutic approach. © 2004 Wiley-Liss, Inc. Key words: angiogenesis; endothelial cells; glioma cells; metalloproteinase-2; migration; proliferation; X raysMalignant gliomas, the most common type of brain tumors in adults, present a remarkable degree of neovascularisation and invasiveness into surrounding tissues. 1 These features account for their poor prognosis, and although combinations of surgery, radiotherapy and chemotherapy are used, more than 90% of the patients experience local recurrence and their survival is extremely low. These facts stress the need for more effective therapeutic strategies. 2 Rapid cell proliferation and high invasive capacity of glioma cells are crucial for tumor development and progression. Moreover, induction of angiogenesis is an essential prerequisite for tumor growth and spread, and precedes malignant tumor formation. 3 Angiogenesis is a fundamental process by which new blood vessels are formed from pre-existing ones. It is a very important step in reproduction, development and wound healing. Furthermore, angiogenesis is very important in several pathological mechanisms like carcinogenesis, tumor metastasis and inflammation. 4 Radiation is considered to inhibit angiogenesis through damage to the endothelium. 5,6 However, in vivo studies suggest that ionizing radiation induces vascular endothelial growth factor (VEGF) production 7 and enhances both the formation of new blood vessels 8 -11 and the secondary development of tumors. 11-13 We have previously shown in the in vivo system of the chicken embryo chorioallantoic membrane (CAM) that X-rays enhance angiogenesis induced by C6 glioma cells inoculated onto the tissue immediately after irradiation...

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confidence: 99%

Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro

Parthymou

Kardamakis

Pavlopoulos

et al. 2004

Intl Journal of Cancer

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“…1 It has been reported that the combination of chemotherapy and radiation does not produce additive or synergistic effects in regards to the treatment of gliomas. [2][3][4] Radiation therapy has a major role in the treatment of patients with most tumor types and can increase the cure rate or prolong survival. 1 Ionizing radiation may also aid in the treatment of recurrences in patients treated initially with surgery alone.…”

Section: A New Hope For Treatment Of Glioblastomasmentioning

confidence: 99%

A New Hope for Treatment of Glioblastomas

Rodriguez-Mora

Franklin

McCubrey³

2003

Cancer Biology & Therapy

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“…Chemotherapies other than those based on nitrosureas have been tested in the treatment of GB with interesting results in vitro which were, however, not confirmed in vivo in a number of studies. This difference in tumor sensitivity could be explained by different proliferation rates, heterogeneity of the tumor cells, presence of the blood-brain barrier, tumor vascularity, extracellular matrix, and different oxygenation and pH values in and around the tumor areas as some particularities of molecular pathways in the in vivo microenvironment [5]. Paclitaxel is a cytotoxic agent that promotes microtubule assembly and inhibits microtubule depolymerization with consequent blocks in dividing cells at the G2/M phase of the cell cycle [6][7][8].…”

Section: Concurrent Chemoradiotherapy With Weekly Paclitaxel In Maligmentioning

confidence: 99%

Concurrent Chemoradiotherapy with Weekly Paclitaxel in Malignant Cerebral Glioma Treatment

Montemor

Peria²,

Monti³

et al. 2008

Onkologie

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Background: Anaplastic astrocytomas (AA) and glioblastomas (GB) are the most common malignant gliomas, and despite newly developed drugs and combined treatments, they still have an adverse prognosis. Paclitaxel is a cytotoxic agent with radiosensitizing properties and exerts objective growth inhibition in glioma tumor cells. Patients and Methods: From 1998 to 2002, 61 microneurosurgically treated patients were randomized to group I (18 GB, 14 AA) which received radiotherapy and weekly paclitaxel at dose of 100 mg/m², and group II (21 GB, 8 AA) which received only radiotherapy as a complementary treatment. Results: Median overall survival was 27.96 months in group I and 23.06 months in group II with no statistical difference. The 12-month survival was 81% in group I and 76% in group II. Kaplan-Meier curves of both groups did not demonstrate any difference. Analysis of each histological subgroup (AA or GB) also showed no statistical difference in the survival curves. All 427 cycles were well tolerated with no treatment-associated deaths. Conclusions: Chemoradiotherapy with weekly paclitaxel is safe and tolerable although there was no increase in the overall survival and 12-month survival of malignant glioma patients. Further investigations modulating the paclitaxel entrance and delivery into the brain should be encouraged.

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Radiochemotherapy of Malignant Glioma in Adults

Cited by 62 publications

References 119 publications

Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro

Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro

A New Hope for Treatment of Glioblastomas

Concurrent Chemoradiotherapy with Weekly Paclitaxel in Malignant Cerebral Glioma Treatment

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