Preface

Glioblastoma remains one of the deadliest of human cancers, with almost uniform fatality of those afflicted. Any potential hope of improved clinical outcome would necessarily be grounded in advances in tumor imaging as it relates to biologic tenets and therapeutic strategies. It is in this context that this compendium is assembled. The selected articles are meant to highlight novel paradigms in hopes of stimulating thoughts that may ultimately contribute to meaningful improvement in clinical outcome. Emphasis was placed on key concepts as they relate to clinical translation. I hope that the work will contribute to the collective effort to ultimately cure the devastating disease of glioblastoma.

> **Clark C. Chen, M.D., Ph.D.**  University of California, San Diego USA

X Preface

**Part 1** 

**Biology of Malignant Gliomas** 

**Part 1** 

**Biology of Malignant Gliomas** 

X Preface

**1** 

**Radiobiology of Radioresistant Glioblastoma** 

Therapy of glioblastoma has been very problematic with disappointing results using multiple therapeutic approaches. In general, glioblastomas are considered radioresistant tumors with different radiation modalities failing to control them in the clinic. However a comprehensive and detailed analysis of the radiosensitivity of glioblastoma cells has not been performed. We now present such an analysis in this chapter seeking a better definition of patterns of radiosensitivity in glioblastomas compared to other tumor cells. These data show that some glioblastomas have unusual responses to radiation that may render them more resistant to some forms of radiotherapy but also render them amenable to exploitation

Multiple mechanisms have been proposed to be associated with radioresistance in human glioblastoma cells: Bao et al (1) have suggested increased DNA damage response. Karim et al (2) have proposed differential cyclo-oxygenase response in radioresistant glios. Brandani et al (3) have suggested HSP 70 elevation. Akuguka et al (4) have suggested increased rates in DNA double strand break rejoining association with micronuclei. Scmidberger et al (5) observed variation interferon-induced β associates with increased radiosensitivity in four out of five glioblastomas. Yao et al (6) suggest variation in cell cycle arrest, modulation of the expression of cyclin-dependent kinase inhibitors, and autophagy. Streffer et al (7) showed BCL- family proteins modulate radiosensitivity in human malignant glioma cells. Kraus et al (8) showed aberrant p21 regulation in radioresistant primary glioblastoma multiforme cells bearing wild-type p53. Haas-Kogan (9) et al showed p53 function influences the effect of fractionated radiotherapy on glioblastoma tumors. Hsiao et al (10) showed functional expression of human p21(WAF1/CIP1) gene in rat glioma cells suppresses tumor growth in vivo and induces radiosensitivity. Yount et al (11) showed cell cycle synchrony unmasks the influence of p53 function on radiosensitivity of human glioblastoma cells. Britten et al (12) showed differential level of DSB repair fidelity effected by nuclear protein extracts derived from radiosensitive and radioresistant human tumour cells. Guichard et al (13) suggest potentially lethal damage repair as a possible determinant of human tumour radiosensitivity including glioblastoma. Kal et al (14) have suggested rhabdomyosarcomas, similar to glioblastomas are sensitive to low dose-rate irradiation.

**1. Introduction** 

by other forms of radiotherapy.

Jerry R. Williams, Daila S. Gridley and James M. Slater

*Radiation Research Laboratories, Department of Radiation Medicine,* 

*Loma Linda, CA* 

*USA* 

*Loma Linda University and Medical Center,* 
