This proposal is to study the effects of local hyperthermia alone, ionizing radiation alone, and these two treatment modalities combined on the development of lymphatic and hematogenous metastases. These studies will be conducted in C57BL/6 mice bearing syngeneic poorly immunogenic melanomas in their feet, the precise metastatic potential of which is related to primary tumor size. Treatment will be done at two primary tumor sizes, either microscopic (mic) or macroscopic (mac) in order to address the possible contribution of tumor blood supply to the mechanisms of metastasis in this model. The primary tumor and regional lymph nodes will be surgically removed at intervals after treatment and metastases examined histologically. Mice will be sacrificed at precisely defined times in order to quantitate the incidence and numbers of metastases in lungs, ovaries and other systemic sites. The final experiments proposed will be to examine the effects of these modalities on overall survival. The results of these studies will provide evidence for the role of hyperthermia and ionizing radiation on the development of metastases from primary tumors following treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043709-03
Application #
3185999
Study Section
Radiation Study Section (RAD)
Project Start
1986-12-01
Project End
1990-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Henry Ford Health System
Department
Type
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Nathanson, S D; Avery, M; Anaya, P et al. (1997) Lymphatic diameters and radionuclide clearance in a murine melanoma model. Arch Surg 132:311-5
Nathanson, S D; Anaya, P; Avery, M et al. (1997) Sentinel lymph node metastasis in experimental melanoma: relationships among primary tumor size, lymphatic vessel diameter and 99mTc-labeled human serum albumin clearance. Ann Surg Oncol 4:161-8
Nathanson, S D; Anaya, P; Karvelis, K C et al. (1997) Sentinel lymph node uptake of two different technetium-labeled radiocolloids,. Ann Surg Oncol 4:104-10
Nathanson, S D; Nelson, L; Karvelis, K C (1996) Rates of flow of technetium 99m--labeled human serum albumin from peripheral injection sites to sentinel lymph nodes. Ann Surg Oncol 3:329-35
Nathanson, S D; Nelson, L T; Lee, M (1993) A spontaneous subcutaneous tumor in C57BL/6 mice that metastasizes to the liver. Clin Exp Metastasis 11:45-54
Avery, M; Nathanson, S D; Hetzel, F W (1992) Lymph flow from murine footpad tumors before and after sublethal hyperthermia. Radiat Res 132:50-3
Cerra, R F; Nathanson, S D (1991) Chemotactic activity present in liver extracellular matrix. Clin Exp Metastasis 9:39-49
Nathanson, S D; Nelson, L; Anaya, P et al. (1991) Development of lymph node and pulmonary metastases after local irradiation and hyperthermia of footpad melanomas. Clin Exp Metastasis 9:377-92
Nathanson, S D; Cerra, R F; Hetzel, F W et al. (1990) Changes associated with metastasis in B16-F1 melanoma cells surviving heat. Arch Surg 125:216-9
Nathanson, S D; Westrick, P; Anaya, P et al. (1989) Relationship of spontaneous regional lymph node metastases to dose of local irradiation of primary B16 melanomas. Cancer Res 49:4412-6

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