Intrinsic and Extrinsic Characteristics of Human Tumors Relevant to Radiosurgery: Comparative Cellular Radiosensitivity and Hypoxic Percentages

Leith, John T.; Cook, Susan C.; Chougule, Prakash; Calabresi, Paul; Wahlberg, L.; Lindquist, Christer; Epstein, Miran

doi:10.1007/978-3-7091-9371-6_5

Cited by 50 publications

(27 citation statements)

References 34 publications

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“…This analysis revealed a previously unrecognized defect in the G 2 DNA damage checkpoint of DU145 cells. DU145 cells are among the most radioresistant cancer cell lines examined to date 47 and their inability to maintain a G 2 arrest may provide for a genetically unstable environment and accumulation of genetic mutations that could ultimately contribute to their radioresistance. 48 DNA repair has previously been investigated in irradiated CaP cell lines.…”

Section: Discussionmentioning

confidence: 99%

A Dominant Role for p53-Dependent Cellular Senescence in Radiosensitization of Human Prostate Cancer Cells

Lehmann

McCubrey²,

Jefferson³

et al. 2007

Cell Cycle

106

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ACKnoWLeDgeMenTSSupported in part by grants from the NIH (R01098195 to J.A.M.) and the Brody Brothers Foundation Endowment (#997729 to J.A.M. and D.M.T.). ReportA Dominant Role for p53-Dependent Cellular Senescence in Radiosensitization of Human Prostate Cancer Cells ABSTrACT Because p53 inactivation may limit the effectiveness of radiation therapy for localized prostate cancer, it is important to understand how this gene regulates clonogenic survival after an exposure to ionizing radiation. Here, we show that premature cellular senescence is the principal mode of cell death accounting for the radiosensitivity of human prostate cancer cell lines retaining p53 function. Alternative stress response pathways controlled by this tumor suppressor, including cell cycle arrest, DNA damage repair, mitotic catastrophe and apoptosis, contributed significantly less to radiation-induced clonogenic death. Using a dominant negative C-terminal fragment of p53, we present the first evidence that a complete loss of endogenous p53 function is sufficient to limit the irradiation-induced senescence and clonogenic death of prostate cancer cells. Conversely, inheritance of wild-type p53 by prostate cancer cells lacking a functional allele of this gene (i.e., DU145) significantly increases clonogenic death through p53-dependent cellular senescence and apoptotic pathways. Our data provide evidence that mutations of even one p53 allele may be sufficient to alter their clonogenic fate. In addition, they support the idea that the p53 pathway can be used as a specific target for enhancing the radiosensitivity of prostate cancer cells. Activation of p53 by the drug nutlin-3 is shown to be an effective radiosensitizer of prostate cancer cells retaining functional alleles of p53 and this effect was entirely attributable to an increased induction of p53-dependent cellular senescence.

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Section: Discussionmentioning

confidence: 99%

A Dominant Role for p53-Dependent Cellular Senescence in Radiosensitization of Human Prostate Cancer Cells

Lehmann

McCubrey²,

Jefferson³

et al. 2007

Cell Cycle

106

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“…Primary GBM, on the other hand, is notorious for its resistance to radiation, and complete response on MRI scan after treatment is exceptional. One of the traditional explanations to the radioresistance of GBM is the high number of anoxic tumor cells adjacent to the necrosis inherent in larger tumors (Kocher et al, 2000;Leith et al, 1994;Okunieff et al, 1993). In the A P R I L 2 0 0 2 cases presented, however, the patients had small deposits that lacked a necrotic component by MRI criteria and that were well vascularized (Figs.…”

Section: Discussionmentioning

confidence: 91%

Intractable vomiting from glioblastoma metastatic to the fourth ventricle: Three case studies

Hassenbusch¹,

Maor²,

Pfeffer³

et al. 2002

Neuro-Oncol

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Dissemination of malignant glioma to the fourth ventricle with metastatic deposits and intractable vomiting is rare.Leptomeningeal extension of malignant glioma is an uncommon condition that has been reported in patients with end-stage disease and is usually unresponsive to any treatment modality. We describe 3 patients with progressing recurrent glioblastoma multiforme in whom leptomeningeal invasion manifested itself as intractable vomiting due to tumor metastases in the oor of the fourth ventricle. All patients received additional radiation therapy focused to the posterior fossa, with complete resolution of vomiting occurring within 10 days after irradiation. The remission of symptoms in these patients persisted until their death 3-4 months after the repeat radiation therapy. These reports indicate that additional focused radiation should be considered because of its signi cant therapeutic effect in alleviating intractable nausea and vomiting in patients with glioma metastasized to the posterior fossa. Neuro-Oncology 4, 129-133, 2002 (Posted to Neuro-Oncology [serial online], Doc. 01-053, February 1, 2002 T he clinical picture of tumor invasion of the leptomeninges is well recognized as a problem of systemic cancer (Wasserstrom et al., 1982), but is less frequent in gliomas. A secondary type of leptomeningeal extension of malignant glioma, also called secondary gliomatosis, has been reported and is associated with dis-

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“…4 and 5 it can be seen that our system (minidosimeter/K-Band spectrometer) is able to detect doses of the order of 10 Gy, unlike the work of Mack et al [39] whose minimum dose was 150 Gy to obtain an X-Band EPR spectrum with good S/N ratio with an L-alanine minidosimeter. It is important to note that dose values typically found in radiosurgery treatments are 10 Gy [40,41] making our system, a potential candidate to be used in radiosurgery dosimetry.…”

Section: Resultsmentioning

confidence: 99%

Response of l-alanine and 2-methylalanine minidosimeters for K-Band (24GHz) EPR dosimetry

Chen

Graeff

Baffa

2007

Nuclear Instruments and Methods in Physics Research Section B:

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Intrinsic and Extrinsic Characteristics of Human Tumors Relevant to Radiosurgery: Comparative Cellular Radiosensitivity and Hypoxic Percentages

Cited by 50 publications

References 34 publications

A Dominant Role for p53-Dependent Cellular Senescence in Radiosensitization of Human Prostate Cancer Cells

A Dominant Role for p53-Dependent Cellular Senescence in Radiosensitization of Human Prostate Cancer Cells

Intractable vomiting from glioblastoma metastatic to the fourth ventricle: Three case studies

Response of l-alanine and 2-methylalanine minidosimeters for K-Band (24GHz) EPR dosimetry

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