Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor alpha (TNF), 1 to 500 ng in saline (PBS) or collagen, was applied to the wounds of normal and Adriamycin-impaired mice and wound disruption strength (WDS) and histology were examined. Also wounded mice were administered TNF 25 to 75 micrograms/kg IP daily and WDS was determined. Wound histology was examined 6 months after wounding and local TNF application. Local TNF 5 to 500 ng in PBS did not significantly affect WDS. Local TNF 5 to 50 ng in collagen increased WDS 33% to 65% in Adriamycin-impaired animals (p = 0.05 to p less than 0.02). Local TNF 50 to 500 ng in collagen increased WDS 23% to 49% in normal animals (p = 0.08 to p less than 0.01). Adriamycin-impaired animals demonstrated improved wound histology with local TNF in collagen. Systemic TNF did not significantly affect WDS. Local TNF in collagen did not induce histologic pathology at 6 months. TNF may modulate macrophage function and local TNF in collagen can improve WDS in normal and Adriamycin-impaired animals.
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PMID:Tumor necrosis factor and wound healing. 230 91

Epidermal growth factor receptor (EGFR)-associated protein tyrosine kinase (PTK) complexes have vital anti-apoptotic functions in human breast cancer cells. We have shown previously that targeting the naturally occurring PTK inhibitor genistein to the EGFR-associated PTK complexes using the EGF-Genistein (Gen) conjugate triggers rapid apoptotic cell death in human breast cancer cells and abrogates their in vitro clonogenic growth. In the present study, we examined the in vivo toxicity profile, pharmacokinetics, and anticancer activity of EGF-Gen. No toxicities were observed in mice treated with EGF-Gen at dose levels as high as 40 mg/kg administered i.p. as a single dose or 140 mg/kg administered i.p. over 28 consecutive days. EGF-Gen significantly improved tumor-free survival in a severe combined immune deficiency (SCID) mouse xenograft model of human breast cancer, when it was administered 24 h after inoculation of tumor cells. At 100 microg/kg/day x 10 days (1 mg/kg total dose), which is >100-fold less than the highest tested and nontoxic cumulative dose (ie., 140 mg/kg) in mice, EGF-Gen was more effective than cyclophosphamide (50 mg/kg/day x 2 days), Adriamycin (2.5 mg/kg x 1 day), or methotrexate (0.5 mg/kg x 1 day), the most widely used standard chemotherapeutic drugs for breast cancer, and resulted in 60% long-term tumor-free survival. Furthermore, treating SCID mice with established s.c. human breast cancer xenografts of 0.5-cm diameter with EGF-Gen at this dose level resulted in disappearance of the tumors in two of five mice and >50% shrinkage in three of five mice within 10 days, whereas all of the control tumors in five PBS-treated mice as well as five mice treated with unconjugated Gen (1 mg/kg/day x 10 days) showed >200% increase in diameter during the same observation period. EGF-Gen treatment reduced the growth rate of breast cancer xenografts of 1.0-cm diameter, but unlike with tumors of 0.5-cm diameter, it failed to cause shrinkage or disappearance of these larger tumors. The level of EGF-Gen systemic exposure that was effective in SCID mice was achieved in cynomolgus monkeys without any significant side effects detectable by clinical observation, laboratory studies, or histopathological examination of multiple organs. EGF-Gen might be useful in the treatment of breast cancer as well as other EGFR-positive malignancies.
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PMID:In vivo toxicity, pharmacokinetics, and anticancer activity of Genistein linked to recombinant human epidermal growth factor. 960 69