Clodronate alleviates cachexia and prolongs survival in nude mice xenografted with an anaplastic thyroid carcinoma cell line.
Cancer cachexia is one of the most common manifestations of advanced malignant disease and is frequently associated with decreased survival. Previously, we reported the establishment of a new anaplastic thyroid carcinoma cell line, Thena, and its mouse xenograft, Thena-Nu, which induced cachexia in athymic nude mice. Subsequent studies showed that the addition of clodronate to Thena-Nu cultures reduced cell proliferation as well as cytokine production in a dose- and time-dependent manner. Weekly administration of clodronate induced tumor cytostasis, attenuation of cachexia, as well as prolongation of survival in Thena-Nu-bearing mice. Reduced serum interleukin 6, tumor necrosis factor-alpha, and granulocyte colony stimulating factor levels were detected, whereas, serum leukemia inhibitory factor levels were not reduced. Liver necrosis, observed in tumor-bearing mice, was also improved following clodronate treatment. Discontinuation of clodronate treatment, however, resulted in progressive tumor growth and weight loss. Our results demonstrated that clodronate could exert therapeutic efficacy on amelioration of cancer cachexia in the hosts. Nevertheless, this study also points out that a longer period of treatment is required to maintain these effects.
Wang
Cheng-Hsu
CH
Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung 204, Taiwan.
Shen
Yung-Chi
YC
Hsieh
Jia-Juan
JJ
Yeh
Kun-Yun
KY
Chang
John Wen-Cheng
JW
D000818:Animals; D017209:Apoptosis; D002100:Cachexia / Q000188:drug therapy* / Q000276:immunology; D002277:Carcinoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004002:Clodronic Acid / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D053605:Leukemia Inhibitory Factor; D008099:Liver / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009336:Necrosis; D009368:Neoplasm Transplantation; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004164:Diphosphonates; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D014409:Tumor Necrosis Factor-alpha; D004002:Clodronic Acid; D016179:Granulocyte Colony-Stimulating Factor