Effects of disodium etidronate in murine tumor models

Guaitani, A.; Polentarutti, Nadia; Filippeschi, Stefania; L, Marmonti; Corti, Fabrizio; Italia, C.; Coccioli, Giovanni; Donelli, M.G.; Mantovani, Alberto; Garattini, Silvio

doi:10.1016/0277-5379(84)90017-8

Cited by 33 publications

(11 citation statements)

References 16 publications

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“…This study is the first to describe the spontaneous hematogenous spread of W256 cells from a solid primary tumor over time, and which provides detailed, quantified histologic analysis of distant metastatic target organs, including bone and soft tissues. The model represents a significant advance for the study of bone metastasis compared to other in vivo models which involve the invasion of bone from contiguous intramuscular tumors [15,16], the intraosseous injection of W256 cells [17], or non-spontaneous metastasis via intraarterial injection [10,15,[18][19][20]. Furthermore, several W256 models have employed non-quantitative [15,17] and/or non-histologic methods [9,16,18] such as X-ray analysis [15][16][17][18] in the attempt to detect osteolysis or bone metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…This model has permitted us to establish the pattern of spread of tumor cells, their growth rates in primary and metastatic sites, and their effects on the structure and metabolism of bone. We argue that this model is more relevant to mechanisms of bone metastasis than other in vivo models which involve direct invasion of bone from contiguous intramuscular tumor [15,16], intraosseous injection of W256 cells [17] or non-spontaneous metastasis via intra-arterial injection [10,15,[18][19][20]. This is the first detailed study to describe the spontaneous hematogenous spread of W256 cells from a solid primary tumor over time, and provides quantified histologic analysis of distant metastatic target organs, including bone and soft tissues.…”

Section: Introductionmentioning

confidence: 99%

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A quantitative model for spontaneous bone metastasis: evidence for a mitogenic effect of bone on Walker 256 cancer cells

et al. 1992

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A new model for the study of spontaneous bone metastasis has been developed which allows for the quantification of metastatic tumor burden and cancer cell growth rate, and which describes the progressive changes in bone morphology. Walker 256 (W256) cells or vehicle were injected into the left upper thigh muscle of male Fischer rats, which were killed 7, 10 or 14 days later. By day 7, metastases had appeared in the distal femur, in the glomeruli of the kidney, and diffusely throughout the liver and lungs. The extent of tumor burden in these organs increased over time. In the femur, 14 days of tumor burden was associated with a 53 +/- 10% decrease in trabecular bone content, a 61 +/- 15% increase in osteoclast surface, and a 95 +/- 10% decrease in osteoblast surface, as compared with non-tumor-bearing controls. By autoradiography, metastatic tumor cells in all organs were determined to have greater growth rates than did cells in the primary tumor. However, within the femur, W256 cells located adjacent to trabecular bone surfaces had a 33 +/- 7% greater growth rate than did W256 cells located > 50 microns from bone surfaces (P < 0.05), suggesting a mitogenic effect of bone.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A quantitative model for spontaneous bone metastasis: evidence for a mitogenic effect of bone on Walker 256 cancer cells

et al. 1992

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“…Etidronat Allererste Hinweise auf eine Reduktion osteolytischer Läsionen durch eine frühzeitige Bisphosphonattherapie wurden bereits beim Etidronat gefunden [26,27]. Nemoto et al [28] …”

Section: Metastasenprophylaxe Im Tiermodellunclassified

Bisphosphonate in der adjuvanten Therapie des Mammakarzinoms – Pathophysiologie, Tiermodelle und erste klinische Erfahrungen

Diel¹

1998

Gynäkol Geburtshilfliche Rundsch

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“…Furthermore bisphosphonates are able to hamper bone metastases by inhibiting the osteoclastic bone resorption [3][4][5]. These substances, however, were not active in killing tumor cells themselves [3,6,7]. As a new approach we therefore constructed bisphosphonates linked to cytostatic agents in order to obtain bifunctional agents which were expected to be active in bone tumors or bone metastases.…”

Section: Introductionmentioning

confidence: 99%

In vivo and in vitro investigations on biological effects of aromatic bis-(2-chloroethyl)amino-bisphosphonic acids, new agents proposed for chemotherapy of bone tumors: cytostatic activity in rat osteosarcoma; toxicity and genotoxicity in liver and bone marrow; mutagenicity in S. Typhimurium

Pool¹,

Berger²,

Schlehofer³

et al. 1988

Invest New Drugs

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Two new aromatic bis-(2-chloroethyl)-amino derivatives (BCMP and BAD) which are linked to osteotropic bisphosphonates were investigated for their therapeutical efficacy in rat osteosarcoma. Furthermore their genotoxic potential in vitro was determined in S. typhimurium and in mammalian cells. Finally, parameters for toxicity and genotoxicity were determined in liver and bone marrow cells following in vivo treatment. It was shown that BAD was of higher therapeutic effectiveness than BCMP. Both compounds induced approximately a two fold increase of his+ revertants in S. typhimurium TA1535 following metabolic activation by subcellular liver fractions. Both compounds also induced amplification of SV40 DNA in SV40 transformed cells (CO631). This endpoint may be of importance for acquired resistancy of cells during therapy. DNA-single strand breaks were induced by BCMP but not by BAD in liver cells and CO631 cell line. Following in vivo treatment BCMP was of higher genotoxic activity in liver cells than BAD. In comparison, genotoxicity of both compounds was much lower in bone marrow cells than in liver cells. BCMP was again more potent than BAD in inducing DNA single strand breaks, whereas BAD was more toxic. The higher therapeutic efficacy of BAD together with its lower genotoxic properties makes this compound superior to BCMP as a candidate for applied chemotherapy in humans.

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Effects of disodium etidronate in murine tumor models

Cited by 33 publications

References 16 publications

A quantitative model for spontaneous bone metastasis: evidence for a mitogenic effect of bone on Walker 256 cancer cells

A quantitative model for spontaneous bone metastasis: evidence for a mitogenic effect of bone on Walker 256 cancer cells

Bisphosphonate in der adjuvanten Therapie des Mammakarzinoms – Pathophysiologie, Tiermodelle und erste klinische Erfahrungen

In vivo and in vitro investigations on biological effects of aromatic bis-(2-chloroethyl)amino-bisphosphonic acids, new agents proposed for chemotherapy of bone tumors: cytostatic activity in rat osteosarcoma; toxicity and genotoxicity in liver and bone marrow; mutagenicity in S. Typhimurium

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