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Carboplatin is a chemotherapy drug used to treat solid tumors but also causes bone loss and muscle atrophy and weakness. Bone loss contributes to muscle weakness through bone-muscle crosstalk which is prevented with the bisphosphonate zoledronic acid (ZA). We treated mice with carboplatin in the presence or absence of ZA to assess the impact of bone resorption on muscle. Carboplatin caused loss of body weight, muscle mass, and bone mass, and also led to muscle weakness as early as 7 days after treatment. Mice treated with carboplatin and ZA lost body weight and muscle mass but did not lose bone mass. In addition, muscle function in mice treated with ZA was similar to control animals. We also used the anti-TGFβ antibody (1D11) to prevent carboplatin-induced bone loss and showed similar results to ZA treated mice. We found that atrogin-1 mRNA expression was increased in muscle from mice treated with carboplatin, which explained muscle atrophy. In mice treated with carboplatin for 1 or 3 days, we did not observe any bone or muscle loss, or muscle weakness. In addition, reduced caloric intake in the carboplatin treated mice did not cause loss of bone or muscle mass, or muscle weakness. Our results show that blocking carboplatin-induced bone resorption is sufficient to prevent skeletal muscle weakness and suggests another benefit to bone therapy beyond bone in patients receiving chemotherapy. This article is protected by copyright. All rights reserved.
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Progressive muscle injury and weakness are hallmarks of Duchenne muscular dystrophy. We showed previously that quercetin (Q) partially protected dystrophic limb muscles from disease-related injury. As...
Age-related skeletal muscle atrophy is a very common and serious condition that remains poorly understood at the molecular level. Several lines of evidence have suggested that the tumor suppressor p53...
Decreased exercise capacity, which is an independent predictor of the poor prognosis of patients with heart failure (HF), is attributed to markedly impaired skeletal muscle mitochondrial function and ...
Sirtuin 1 (SIRT1) and general control of amino acid synthesis 5 (GCN5) regulate mitochondrial biogenesis via opposing modulation of peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1...
Immuno-inflammation contributes to the pathogenesis of Duchenne muscular dystrophy (DMD), characterized by progressive muscle degeneration and weakness. The nucleotide-binding oligomerization domain (...
The overall purpose of this research is to evaluate the safety and side effects of zoledronic acid (also known as Zometa) in patients before they have surgery to remove the cancer.
The purpose of this study is to assess the effects of zoledronic acid administered at the same time with teriparatide compared to zoledronic acid alone and teriparatide alone on bone mine...
The purpose of this study is to demonstrate that patients with Paget's disease of the bone who had responded to zoledronic acid treatment as participants in the core registration studies C...
This trial will be a pilot study to find out if zoledronic acid improves the response to chemotherapy in high grade osteosarcoma. In arm A of the study, 40 adult patients will be randomise...
Osteoporosis prevention is important in patients with osteopenia (low bone density). This study will test the safety and efficacy of zoledronic acid in patients diagnosed with osteopenia.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
A strain of mice arising from a spontaneous MUTATION (mdx) in inbred C57BL mice. This mutation is X chromosome-linked and produces viable homozygous animals that lack the muscle protein DYSTROPHIN, have high serum levels of muscle ENZYMES, and possess histological lesions similar to human MUSCULAR DYSTROPHY. The histological features, linkage, and map position of mdx make these mice a worthy animal model of DUCHENNE MUSCULAR DYSTROPHY.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.
A system of therapeutics founded by Samuel Hahnemann (1755-1843), based on the Law of Similars where "like cures like". Diseases are treated by highly diluted substances that cause, in healthy persons, symptoms like those of the disease to be treated. The dilutions are repeated so many times that there is less than one molecule per dose and it is suggested that benefit is from the energetic life force of the original substance.
Surgical reinnervation of a denervated peripheral target using a healthy donor nerve and/or its proximal stump. The direct connection is usually made to a healthy postlesional distal portion of a non-functioning nerve or implanted directly into denervated muscle or insensitive skin. Nerve sprouts will grow from the transferred nerve into the denervated elements and establish contact between them and the neurons that formerly controlled another area.
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...
Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...