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The experiments in Group A will be conducted in order to determine if human tumor microvascular endothelium displays similar dose parameters as mouse tumor endothelium, and if the microvascular endothelium of tumors of different types behaves in a similar fashion in its response to IR.

The experiments in Group B will be conducted in order to determine if tumor endothelium isolated to near homogeneity demonstrates dose parameters similar to those used in single dose radiotherapy of brain tumors.

Tumors will be sliced into 0.5cm fragments, incubated in culture medium and then irradiated to evaluate the kinetics and dose-dependencies of the endothelial apoptotic response. We will irradiate tumor fragments ex vivo at 0, 7, 13, 15, 17, and 25 Gy.

Ionizing radiation (IR) therapy

Tissue fragments of a total quantity of at least a 4x4x4 cm3 will be required. For each tumor a paraffin block will also be made for routine staining and IHC. Endothelial cell populations (at least 500 cells) will then be exposed to radiation at 0, 7, 11, 13, 15, 17, and 25 Gy and harvested at 4, 5 and 8 hours post IR.

Ionizing radiation (IR)

Michael Zelefsky, M.D.

Doctors will take some tissue from the tissue removed during surgery in order to study how the blood vessels of the tumor respond to radiation therapy. The tissue obtained will be used to determine how these tumor blood vessels respond to radiation therapy delivered to the tumor, after it has been removed. This radiation is delivered in the research lab. This research is being conducted in order to develop new methods to treat tumors by radiation therapy. No additional surgery will be performed to obtain these samples, and only materials that remain after all diagnostic testing has been completed will be used.

The goal of this study is to determine if concepts established in mouse models of the tumor microvascular response to ionizing radiation (IR) therapy are applicable to human tumors in order to begin to establish that the engagement of the endothelial response is a valid target for IR in human tumors. A portion of tumor will be isolated from individuals who have signed informed consent for this protocol and are undergoing surgery on the Neurosurgery, Colorectal, and Gynecology, Head and Neck, Urology, and Hepatobiliary Services at Memorial Sloan-Kettering Cancer Center. Tumor tissue will be obtained from the surgical sample in pathology after adequate specimens have been obtained for diagnostic purposes. Tumor tissue will be irradiated ex vivo and the microvascular endothelial response will be determined. From specimens of adequate size, a pure tumor endothelial cell population will be isolated and the response to IR will be determined.

Primary Outcomes:

* To determine if human tumor microvascular endothelium displays similar dose parameters as mouse tumor endothelium.

Secondary Outcomes:

* To determine if tumor endothelium isolated to near homogeneity demonstrates dose parameters similar to those used in single dose radiotherapy of brain tumors.
* To determine if the microvascular endothelium of tumors of different types behaves in a similar fashion in its response to IR.

An Analysis of the Response of Human Tumor Microvascular Endothelium to Ionizing Radiation

The peak apoptotic radiation response will be obtained for each of the tumor type and the result compared to that of the mouse experiments in Garcia-Barros (no formal testing only qualitative statements).

National Cancer Institute (NCI)

Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for ionizing radiation (ir)