The Role of the Muscle-nervous System Interface in Cancer Cachexia

Study Overview
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Brief Summary
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Sarcopenia is an important component of cachexia associated with cancer, and their high incidence in cancer patients emphasizes the need for a better understanding of its mechanisms, which can result in better therapeutic interventions to reverse this situation and improve the prognosis. Our hypothesis is that the plasma concentration of IL-6 and c-terminal agrin is directly correlated with the loss of muscle mass and development of cachexia.

Detailed Description
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The agrin is a protein that acts on neuromuscular junctions (NMJs) promoting stabilization of same, which results in the maintenance and growth of muscle fibers, but the cleavage of agrin, a process by which is formed the agrin fragment C-terminus (CAF), has been linked to the development of sarcopenia, because its presence is directly linked to the reduction in the number of muscle fibers, increasing the heterogeneity of fiber size, presence of Central cores and increasing the proportion of type I fibers and consequently a greater degradation of lean body mass. Studies in mice show that the greatest cleavage of agrin carries on development of sarcopenia and human studies report that individuals with higher serum levels of sarcopenia CAF compared to individuals without sarcopenia. Therefore, aiming at the complexity of cancer associated with the cachexia and the great importance of the maintenance of lean body mass to a better prognosis in disease, is of fundamental importance to elucidate the role of CAF and the factors associated with sarcopenia, the possible use of these proteins for diagnosis and the contribution that this clarification could bring in clinical therapy.

Official Title
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The Role of the Muscle-nervous System Interface in Cancer Cachexia

Conditions
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Cachexia; Cancer; Sarcopenia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: cancer diagnosis Exclusion Criteria: continuously use of anti-inflammatory medications; present renal and/or liver failure, AIDS, inflammatory bowel disease or chronic inflammatory processes not related to cachexia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group with cancer cachexia (CTB)<br>For diagnosis of cachexia it will be used the following criteria (Evans et al., 2008) | |
| Group without cancer cachexia (TB)<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Agrin fragment c-terminus CAF in cancer and cancer cachexia | To measure the contents of agrin fragment c-terminus (CAF) in plasma of patient with cancer and cancer cachexia. | 1 month | 
| Agrin fragment c-terminus CAF in cancer sarcopenia | To analyze correlation between Agrin fragment c-terminus CAF and the lean body mass (CT-scan estimated) of patients with cancer and with cancer cachexia. | 1 month | 
| Agrin fragment c-terminus CAF and IL-6 levels | To correlate levels of agrin fragment c-terminus (CAF) and IL-6 plasma levels in patients with cancer and with cancer cachexia. | 1 month | 
| Agrin fragment c-terminus (CAF) and IL-6 and lean body mass | To correlate levels of agrin fragment c-terminus (CAF) and IL-6 with the lean body mass | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Agrin Fragment C-terminus (CAF)