The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice.

The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice. Research Abstract Details 

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The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice. Abstract Text:

S H Tannehill-Gregg,A L Levine,M V P Nadella,H Iguchi,T J Rosol,

The pathogenesis of bone metastases may require the activation of osteoclasts by tumor-secreted factors, which promote important interactions with the bone microenvironment. We utilized an intratibial model of bone metastasis with bioluminescent imaging (BLI) to measure the effect of osteoclast inhibition on the interaction of human lung cancer cells with bone, and on tumor growth. Mice were injected with luciferase-transduced tumor cells (HARA, human pulmonary squamous carcinoma) and divided into three groups: (1) untreated, (2) twice weekly treatment with the bisphosphonate zoledronic acid (ZOL), or (3) osteoprotegerin (OPG). Histomorphometry and imaging were used to evaluate tumor burden, and parameters of osteoclast activity. Mice in the treated groups had increased bone density and decreased osteoclast numbers in nontumor-bearing tibiae. There was greater than 60% reduction in mean tumor volume in both treatment groups when evaluated by histomorphometry (P = 0.06 [OPG], P = 0.07 [ZOL]). However, bioluminescent imaging failed to show a reduction in tumor burden due to wide variability in the data. Osteoclast numbers along tumor-associated bone were significantly increased compared to tumor-free bone, and were not reduced by either treatment. Plasma calcium concentration was increased in all groups. Plasma tartrate-resistant acid phosphatase 5b was reduced in both treatment groups. Plasma PTHrP was significantly increased in the untreated tumor-bearing group, but was not significantly different in the two treatment groups compared to normal mice. OPG or ZOL did not change tumor cell proliferation, but ZOL increased HARA cell apoptosis. OPG and ZOL reduced tumor growth in the tibiae of treated mice, however, PTHrP production by HARA cells may have resulted in a high concentration in the bone microenvironment, partially overriding the antiosteoclast effects of both OPG and ZOL.

The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice. Publishing Authors By Initials

SH Tannehill-Gregg,AL Levine,MV Nadella,H Iguchi,TJ Rosol,

For similar surgical procedures, operative: transplantation: transplantation, heterologous research abstracts see: surgical procedures, operative: transplantation: transplantation, heterologous research

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The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Clinical & experimental metastasis

VOLUME: 23

Page Numbers: 19-31

Journal Abbreviation: Clin. Exp. Metastasis

ISSN: 0262-0898

DAY: 20

MONTH: 05

YEAR: 2006

The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8409970

The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice. Keywords Mesh Terms:

KEYWORDS: Transplantation, Heterologous

MESH TERMS: pharmacology

Chemical & Substance for Abstract: The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice. Information

Substance Name: zoledronic acid

Registry Number: 118072-93-8

Grant and Affiliation Information for The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice.

AFFILIATION: Bristol-Myers Squibb Company, Pharmaceutical Research Institute, Evansville, IN, USA.

Country: Netherlands

AGENCY: United States NCRR

GRANT: S10 RR17841

ACRONYM: RR

MEDLINETA: Clin Exp Metastasis

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