Chronic Radiation Bone Toxicity is Associated with Decreased Perfusion Without Elevation of Circulating or Soft Tissue TGFβ or TNFα

Okunieff, Paul; Wang, Xin; Li, Ming; Sabet, Hjeer; Huang, Kundi; Grieg, J. Robert; Williams, Jacqueline P.; Rubin, Philip; Ding, Ivan

doi:10.1007/978-1-4615-4863-8_38

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…15 The chemokine multiple template includes: MCP-1, MIP-1␣, MIP-1␤, MIP-2, Rantes, Eotaxin, and ip-10. The frozen tissue was pulverized, and then dissolved in TRI Reagent (Molecular Research Center, OH, U.S.A.) according to the manufacturer's specifications.…”

Section: Tumor Tissue Rna Isolation and Rnase Protection Assaysmentioning

confidence: 99%

Celecoxib Reduces Skin Damage After Radiation

Liang

Liu

et al. 2003

American Journal of Clinical Oncology

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Inflammatory cytokine and chemokine production is mediated, at least in part, by prostaglandin E (PGE2). Cyclooxygenases, COX-1 and COX-2, are two key enzymes in the conversion of arachidonic acid to PGE2. Radiation induces the overproduction of cytokines and chemokines, and it also increases PGE2 production, both locally and systemically. In this study, we tested the effects of a COX-2 inhibitor (celecoxib) after 50 Gy radiation of MCa-35 tumor and cutaneous tissues of C3H/He mice. Preclinical toxicity endpoints and associated alterations in chemokine production and cellular infiltrates were measured. Celecoxib was given by daily gavage (50 mg/kg for 15 days), with the first dose delivered either 2 hours before, 2 days after, or 7 days after a single dose of radiation. Celecoxib-treated animals had less inflammation of the dermis compared with saline-treated controls. Severe skin dermatitis occurred in 23.8% (5/21) of mice treated with 50 Gy, whereas only 17.6%, 5.3%, and 11.1% of mice in the 2-hour pre-, or the 2-day post-, and 7-day postirradiation groups, respectively, had severe dermatitis on day 20. The decreased skin toxicity scores were associated with a reduction of both blood vessels and focal necrosis in MCa-35 tumors. Celecoxib also significantly decreased C-C family chemokine (Rantes and MCP-1) mRNA expression in irradiated skin tissues, but not in tumor tissues, which was accompanied by a decrease in skin mRNA expression of both C-C (CCR2 and CCR5) and C-X-C (CXCR2 and CXCR4) chemokine receptors. A significant positive correlation was also found between skin damage (skin scores) and chemokine and its receptor mRNA expression in radiation-treated mice. Finally, celecoxib also decreased the infiltration of monocytes and neutrophils in locally irradiated tumor and surrounding normal tissue. The differential effects of celecoxib on inflammation help to explain the selective protection by celecoxib of irradiated cutaneous tissues without a concurrent protection of MCa-35 tumors.

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Section: Tumor Tissue Rna Isolation and Rnase Protection Assaysmentioning

confidence: 99%

Celecoxib Reduces Skin Damage After Radiation

Liang

Liu

et al. 2003

American Journal of Clinical Oncology

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“…5,18,33 Other FGF isoforms can also radioprotect in a variety of circumstances. For example, acidic FGF has shown a spectrum of effects similar to bFGF, although usually with less efficiency, and FGF7 (also known as KGF) appears to protect the small bowel to a greater extent than Cy/TBI with high bFGF levels.…”

Section: Discussionmentioning

confidence: 99%

Circulating basic fibroblast growth factor declines during Cy/TBI bone marrow transplantation

Okunieff

Barrett

Phang

et al. 1999

Bone Marrow Transplant

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Summary:Basic fibroblast growth factor (bFGF) inhibits radiation-induced apoptosis, and radioprotects haematopoietic, cartilage growth plate, pulmonary and gastrointestinal tissues. Conversely, chronic overexpression of bFGF may promote fibrosis. We measured the endogenous circulating bFGF in blood of patients undergoing conditioning TBI. Twenty-six patients with haematopoietic malignancies were conditioned with cyclophosphamide/TBI for allogeneic BMT. Daily blood samples were collected each morning prior to, during, and for several days after TBI. bFGF levels in plasma of normal volunteers are 0.8-26 pg/ml. bFGF was below detectability in 22%, 30% and 45% of patients pre-TBI, during TBI or post-TBI respectively. Mean circulating plasma levels of bFGF decreased from a median of 52 pg/ml pre-TBI to 26 pg/ml during TBI, and to 5 pg/ml post-TBI. Among the 26 patients, 13 had more than one non-detectable plasma bFGF level, an additional five had at least one non-detectable level, and only eight patients had detectable levels in all daily samples. Naturally high levels of bFGF were observed in some patients undergoing fractionated TBI. In contrast, as many as 79% of patients had low bFGF levels in one or more samples. The impact of endogenous bFGF on the tolerance of normal tissues to irradiation is unknown, and warrants further study.

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