Effect of the specific cyclooxygenase-2 inhibitor meloxicam on tumour growth and cachexia in a murine model

Hussey, HJ; Tisdale, Michael J.

doi:10.1002/1097-0215(20000701)87:1<95::aid-ijc14>3.0.co;2-d

Cited by 60 publications

(32 citation statements)

References 24 publications

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“…Indeed, Porter et al (28) have reported an association between dermcidin expression in breast tumors and a more aggressive clinical course. Similarly, MAC16 tumors, unlike MAC13 tumors, are generally refractory to standard cytotoxic agents (32).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Human Homologue of Proteolysis-Inducing Factor and Its Role in Cancer Cachexia

Monitto¹,

Dong

Jen

et al. 2004

Clinical Cancer Research

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Cachexia is an important cause of secondary morbidity and mortality in patients with cancer. Previous studies have suggested that cancer-associated cachexia may be due in part to tumor-specific production and secretion of a glycosylated peptide, proteolysis-inducing factor, originally identified in a murine cancer cachexia model. We report here the cloning of a human cDNA that generates a peptide having high-sequence homology to this proteolysis-inducing factor. Constitutive expression of human proteolysis-inducing factor is low or absent in most normal human tissues but appears to be elevated in some human tumors. Stable forced expression of human proteolysis-inducing factor in multiple murine and human cell lines results in a secreted protein, but no glycosylation of the protein is detected. In addition, tumor xenografts engineered to overexpress human proteolysis-inducing factor protein do not induce cachexia in vivo. These findings raise important questions as to potential cross-species differences in protein sequence and processing of murine proteolysis-inducing factor and human proteolysis-inducing factor, as well as the nature of the relationship between human proteolysis-inducing factor and the development of cancer cachexia.

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Section: Discussionmentioning

confidence: 99%

Characterization of a Human Homologue of Proteolysis-Inducing Factor and Its Role in Cancer Cachexia

Monitto¹,

Dong

Jen

et al. 2004

Clinical Cancer Research

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“…A limited number of studies have indicated the in vivo efficacy of meloxicam against experimental tumors. In one study, a meloxicam dose of 1.0 to 5.0 mg/kg administered daily was shown to be effective, and the drug concentration following a 1.0 mg/kg dose appeared to be achievable in humans (32). However, in another study the effective daily dose of meloxicam was 40 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

Antitumor effects of a cyclooxygenase-2 inhibitor, meloxicam, alone and in combination with radiation and/or 5-fluorouracil in cultured tumor cells

Ayakawa¹

2009

Mol Med Rep

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Abstract.To ascertain whether meloxicam used in a clinical setting as a non-steroidal anti-inflammatory drug (NSAID) warrants preclinical in vivo evaluation as an anticancer agent, we investigated its antitumor effects alone and in combination with radiation and/or 5-fluorouracil (5-FU) in cultured cells. Seven cell lines were examined for cyclooxygenase-2 (COX-2) protein expression by immunoblot analysis, and the HelaS3, SccVii and eMT6 cell lines were selected, expressing relatively high, intermediate, and relatively low COX-2 levels, respectively. Antitumor effects were examined using a colony assay. Among the three cell lines, the effect of meloxicam alone was strongest in SccVii cells. With 24 h of drug exposure, meloxicam at concentrations of 250 and 1250 µM had a definite antitumor effect, dependent on the drug exposure time. The effect of meloxicam in combination with radiation and/or 5-FU was also investigated in the SccVii cells. at a meloxicam concentration of 250 µM, the antitumor effect in combination with radiation or 5-FU was increased compared to the effect of radiation or 5-FU alone; however, the combined effect appeared to be additive. at lower concentrations, meloxicam had no radiosensitizing effect, nor did it enhance the effect of 5-FU. A meloxicam concentration of 250 µM is considerably higher than concentrations obtained in humans taking meloxicam as an nSaid. in conclusion, the antitumor effect of meloxicam was not correlated with the level of COX-2 protein expression. The effect of meloxicam in combination with radiation and/or 5-FU appeared to be additive. To evaluate the possibility of using meloxicam as an anticancer agent, in vivo investigations at clinically relevant drug dose levels are required.

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“…The effect on weight loss was already described for NSAIDs in different tumor models and in patients with cancer-related cachexia. 26,31,32 PGE 2 produced by the tumor can stimulate the secretion of IL-6. Thus, by diminishing PGE 2 synthesis with NSAID treatment, the contribution of IL-6 to the onset of cachexia could be prevented.…”

Section: Discussionmentioning

confidence: 99%

Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs

Peluffo

Stillitani

Rodríguez

et al. 2004

Intl Journal of Cancer

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Mice bearing LP07 lung adenocarcinoma show some characteristics that are similar to those present in patients with NSCLC. LP07 tumor-bearing mice develop the paraneoplastic syndromes of cachexia, leukocytosis and hypercalcemia. These symptoms may be partly due to a systemic inflammatory response. Our aim was to determine if treatment with NSAIDs would lower tumor and metastasis growth and their accompanying syndromes. The nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor celecoxib reduced tumor growth and metastasis outcome in s.c. LP07 tumor-bearing mice. Both drugs also inhibited the development of leukocytosis and the weight loss associated with LP07 progression. Serum levels of the inflammatory cytokines IL-1␤ and IL-6, mediators of cachexia, were modulated by NSAIDs. Inhibition of in vitro migration and invasion and reduction in angiogenesis were attained when cells were treated with either indomethacin or celecoxib. MMP-9 activity was also reduced in conditioned media from LP07 cells treated with celecoxib. These data suggest that several processes implicated in tumor progression can be modulated with NSAID treatment. Improvement in performance status through modulation of cachexia may offer a possibility for combining anti-inflammatory treatments with more aggressive therapies.

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Effect of the specific cyclooxygenase-2 inhibitor meloxicam on tumour growth and cachexia in a murine model

Cited by 60 publications

References 24 publications

Characterization of a Human Homologue of Proteolysis-Inducing Factor and Its Role in Cancer Cachexia

Characterization of a Human Homologue of Proteolysis-Inducing Factor and Its Role in Cancer Cachexia

Antitumor effects of a cyclooxygenase-2 inhibitor, meloxicam, alone and in combination with radiation and/or 5-fluorouracil in cultured tumor cells

Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs

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