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The effect of altered Toll-like receptor 4 signaling on cancer cachexia
- Source :
- Cannon, TY; Guttridge, D; Dahlman, J; George, JR; Lai, V; Shores, C; et al.(2007). The Effect of Altered Toll-like Receptor 4 Signaling on Cancer Cachexia. Archives of Otolaryngology–Head & Neck Surgery, 133(12), 1263-1263. doi: 10.1001/archotol.133.12.1263. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/45v0n8hv, Archives of otolaryngology--head & neck surgery, vol 133, iss 12
- Publication Year :
- 2007
-
Abstract
- Objective To determine whether mice unable to mount an intact inflammatory response because of a Toll-like receptor (TLR) pathway defect will develop less severe cancer cachexia. Design Prospective animal study. Setting Academic research center. Subjects Six- to eight-week-old, female C3H/HeJ mice (17-18 g) and age-, weight-, and sex-matched wild-type C3H/HeN mice, differing in that the HeJ mice have nonfunctional TLR4 due to a TLR4 double mutation (TLR4 d/d ). Intervention The mice were inoculated with equal numbers of SCCF-VII cells and housed in individual cages. Main Outcome Measures Food intake, body weight, pretumor and posttumor body composition, circulating cytokines, and levels of a marker of muscle atrophy were analyzed. Results The wild-type HeN mice weighed less on average than the TLR4 d/d mice (2.6 g vs 4.9 g) ( P = .01). They consumed more food, had smaller tumors, and had less lean body mass and fat mass than the TLR4 d/d mice. Interleukin 1β level was significantly elevated in the tumor-bearing HeN mice (mean gain of 259 pg/mL) but not in the TLR4 d/d mice ( P = .03). Both mouse strains had evidence of muscle atrophy. Conclusions In spite of increased food intake and smaller tumors, the wild-type HeN mice had more severe cachexia than the TLR4 d/d mice. The impaired ability to secrete proinflammatory cytokines such as interleukin 1β may protect these animals from developing severe cancer cachexia. This animal model represents a novel system in which the host contributions to cachexia may be further studied.
- Subjects :
- Cachexia
medicine.medical_treatment
Mice
Tumor Cells, Cultured
2.1 Biological and endogenous factors
Prospective Studies
Receptor
Tumor Markers
Cancer
Mice, Inbred C3H
Cultured
Tumor
Interleukin
General Medicine
Inbred C3H
Muscle atrophy
Tumor Cells
Cytokine
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Disease Progression
Female
medicine.symptom
Signal Transduction
medicine.medical_specialty
Clinical Sciences
Proinflammatory cytokine
Internal medicine
medicine
Biomarkers, Tumor
Animals
Nutrition
Animal
business.industry
Carcinoma
Body Weight
Biological
medicine.disease
Toll-Like Receptor 4
Disease Models, Animal
Endocrinology
Squamous Cell
Otorhinolaryngology
Disease Models
TLR4
Lean body mass
Surgery
business
Biomarkers
Subjects
Details
- ISSN :
- 08864470
- Volume :
- 133
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Archives of otolaryngology--headneck surgery
- Accession number :
- edsair.doi.dedup.....8574a8d60d5aa7b78426e72ae4463994