Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lisofylline is a new methylxanthine. The potential of lisofylline to enhance the response to ionizing radiation of the EMT-6 murine mammary carcinoma in vitro and in vivo was assessed and compared with pentoxifylline. Addition of lisofylline (100 microM) or pentoxifylline (100 microM) from the time of radiation exposure and throughout the time of colony formation did not alter the response of normally oxygenated EMT-6 cells to gamma-radiation delivered at 0.76 Gy/min or 12.3 Gy/min. The dose modifying factor for hypoxic EMT-6 cells by lisofylline or pentoxifylline and radiation delivered at 0.76 Gy/min was 2.3. Higher dose rate radiation (12.3 Gy/min) was more cytotoxic toward hypoxic EMT-6 cells than lower dose rate radiation. The dose modifying factor produced by lisofylline in the high dose rate radiation setting was 1.2. In vivo, using the tumor cell survival assay, lisofylline decreased the shoulder of the radiation survival curve (0.76 Gy/min) by a factor of 1.7 +/- 0.2 while pentoxifylline did not. In the tumor growth delay assay, administration of multiple doses of lisofylline or pentoxifylline along with single dose radiation (0.76 Gy/min) was 1.3, while the radiation dose modifying factor for lisofylline or pentoxifylline administered by continuous infusion was 1.5. Overall, lisofylline was a more effective modifier of gamma-radiation therapy than pentoxifylline, and further investigation of lisofylline in this setting is warranted.
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PMID:Lisofylline as a modifier of radiation therapy. 916 Mar 55

Lisofylline, a dimethylxanthine derivative, has been shown to block the induction of hematopoietic growth inhibitors produced in response to cytotoxic anticancer therapy. In the current study, mice bearing established EMT-6 mammary carcinoma were treated with high dose cyclophosphamide, melphalan, BCNU, 5-fluorouracil or with total body radiation alone or with peripheral blood cells. The effect of lisofylline and/or G-CSF on leukocyte recovery was examined. Lisofylline was as effective as G-CSF in accelerating the recovery of white blood cells and granulocytes after treatment with high dose chemotherapy or total body radiation. Lisofylline alone or along with G-CSF was effective in protecting animals from the weight loss caused by high dose melphalan but not from weight loss caused by other cytotoxic therapies. Administration of lisofylline did not alter the killing of bone marrow CFU-GM by single doses of cyclophosphamide, melphalan or BCNU. However, administration of lisofylline increased the killing of EMT-6 tumor cells taken from the same animals. Administration of lisofylline had no effect on EMT-6 tumor growth. However, treatment with lisofylline along with high dose cyclophosphamide: melphalan, BCNU or 5-fluorouracil significantly increased the tumor growth delay produced by these agents. Overall, in the high dose therapy/EMT-6 mammary carcinoma model, lisofylline selectively enhanced hematopoietic recovery and increased tumor response to cytotoxic therapy.
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PMID:Lisofylline as an adjuvant to high dose cytotoxic therapy. 2152 10