Anorexia-Cachexia

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Samuel N. Breit - One of the best experts on this subject based on the ideXlab platform.

  • Targeting the divergent TGFβ superfamily cytokine MIC-1/GDF15 for therapy of anorexia/cachexia syndromes
    Current Opinion in Supportive and Palliative Care, 2018
    Co-Authors: Vicky Wang-wei Tsai, David A. Brown, Samuel N. Breit
    Abstract:

    Purpose of reviewTo review recent finding on MIC-1/GDF15 and re-evaluate it as a potential target for the therapy of anorexia/cachexia syndromes.Recent findingsMIC-1/GDF15 consistently induces anorexia/cachexia in animal models. Its actions on brainstem feeding centers leads to anorexia, inducing pr

  • Anorexia-Cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15.
    International Journal of Obesity, 2015
    Co-Authors: Vicky Wang-wei Tsai, David A. Brown, A Salis, Samuel N. Breit
    Abstract:

    Anorexia–cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15

  • Anorexia/cachexia of chronic diseases: a role for the TGF-β family cytokine MIC-1/GDF15
    Journal of Cachexia Sarcopenia and Muscle, 2012
    Co-Authors: Vicky W. W. Tsai, David A. Brown, Yasmin Husaini, Rakesh Manandhar, Hong Ping Zhang, Kate Harriott, Lele Jiang, Amanda Sainsbury, Samuel N. Breit
    Abstract:

    Anorexia/cachexia is a common and currently mostly untreatable complication of advanced cancer. It is also a feature of a number of chronic diseases and can also occur as part of the normal ageing process. Over recent years, two different, but sometimes overlapping, processes have been identified to mediate anorexia/cachexia: those that act primarily on muscle reducing its mass and function, and processes that decrease nutrition leading to loss of both fat and muscle. In the case of at least some cancers, the latter process is sometimes driven by marked overexpression of macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15). MIC-1/GDF15 is a transforming growth factor beta (TGF-β) family cytokine that is found in the serum of all normal individuals at an average concentration of about 0.6 ng/ml. Its increased expression in both cancers and other diseases can result in 10–100-fold or more elevation of its serum levels. In experimental animals, serum MIC-1/GDF15 levels at the lower end of this range induce anorexia by direct actions of the circulating cytokine on feeding centres in the brain. Mice with tumours overexpressing MIC-1/GDF15 display decreased food intake, loss of lean and fat mass and cachexia. That this process also mediates anorexia/cachexia in humans is suggested by the fact that there is a direct correlation between the degree of serum MIC-1/GDF15 elevation and the amount of cancer-related weight loss, the first such relationship demonstrated. Further, in experimental animals, weight loss can be reversed by neutralisation of tumour-produced MIC-1/GDF15 with a specific monoclonal antibody, suggesting the possibility of effective therapy of patients with the devastating complication of anorexia/cachexia.

S N Breit - One of the best experts on this subject based on the ideXlab platform.

  • Anorexia–cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15
    International Journal of Obesity, 2016
    Co-Authors: V W W Tsai, D A Brown, A Salis, S N Breit
    Abstract:

    Anorexia–cachexia associated with cancer and other diseases is a common and often fatal condition representing a large area of unmet medical need. It occurs most commonly in advanced cancer and is probably a consequence of molecules released by tumour cells, or tumour-associated interstitial or immune cells. These may then act directly on muscle to cause atrophy and/or may cause anorexia, which then leads to loss of both fat and lean mass. Although the aetiological triggers for this syndrome are not well characterized, recent data suggest that MIC-1/GDF15, a transforming growth factor-beta superfamily cytokine produced in large amounts by cancer cells and as a part of other disease processes, may be an important trigger. This cytokine acts on feeding centres in the hypothalamus and brainstem to cause anorexia leading to loss of lean and fat mass and eventually cachexia. In animal studies, the circulating concentrations of MIC-1/GDF15 required to cause this syndrome are similar to those seen in patients with advanced cancer, and at least some epidemiological studies support an association between MIC-1/GDF15 serum levels and measures of nutrition. This article will discuss its mechanisms of central appetite regulation, and the available data linking this action to anorexia–cachexia syndromes that suggest it is a potential target for therapy of cancer anorexia–cachexia and conversely may also be useful for the treatment of severe obesity.

David Cella - One of the best experts on this subject based on the ideXlab platform.

  • Comprehensive validation of the functional assessment of anorexia/cachexia therapy (FAACT) anorexia/cachexia subscale (A/CS) in lung cancer patients with involuntary weight loss.
    Quality of Life Research, 2019
    Co-Authors: Heather L. Gelhorn, Katharine S. Gries, Rebecca M. Speck, Elizabeth M. Duus, Richard K. Bourne, Dimple Aggarwal, David Cella
    Abstract:

    Comprehensive (qualitative and quantitative) assessments of the 12-item functional assessment of anorexia/cachexia therapy (FAACT) anorexia/cachexia subscale (A/CS) and relevant subscales were undertaken for use in constructing potential endpoints in clinical trials of non-small cell lung cancer (NSCLC) with involuntary weight loss. Eleven participants (≥ 18 years) from six clinical sites with a diagnosis of stage III unresectable or stage IV NSCLC and involuntary weight loss (either ≥ 5% body weight loss within six months prior to screening or screening BMI 

  • Validation and real-world assessment of the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in patients with advanced non-small cell lung cancer and the cancer Anorexia-Cachexia syndrome (CACS)
    Supportive Care in Cancer, 2015
    Co-Authors: Thomas W. Leblanc, David Cella, Greg Samsa, Steven Wolf, Susan C. Locke, Amy P. Abernethy
    Abstract:

    Purpose Patients with cancer Anorexia-Cachexia syndrome (CACS) suffer a significant symptom burden, impaired quality of life (QoL), and shorter survival. Measurement of QoL impairments related to CACS is thereby important both in clinical practice and in research. We aimed to further validate the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in an advanced lung cancer population.

  • Re-validation and shortening of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire
    Quality of Life Research, 2000
    Co-Authors: J. M. Ribaudo, David Cella, Stephen Lloyd, Elizabeth A. Hahn, N S Tchekmedyian, J. Von Roenn, William T. Leslie
    Abstract:

    Purpose: The original Functional Assessment of Anorexia/Cachexia Therapy (FAACT) was designed to measure general aspects of quality of life (QOL) as well as specific anorexia/cachexia-related concerns. Our primary purpose was to reduce the number of anorexia/cachexia subscale items in a manner that either retains or improves reliability, validity and precision. Methods: The FAACT was administered using an interactive computer program that allowed immediate entry of the data. A total of 213 patients were recruited. Results: A combined empirical and conceptual approach led to the reduction of the anorexia/cachexia subscale (A/CS) from 18 to 12 items. A 26-item trial outcome index (TOI) combining physical well-being (PWB), functional well-being (FWB), and the A/CS-12 was highly reliable and sensitive to change in performance status rating (PSR). We found that PWB, FWB, and A/CS-12 subscales performed differently. Specifically, PWB and FWB scores decreased in patients whose (PSR) worsened. However, although A/CS-12 scores were responsive to change in PSR over time, average A/CS-12 scores of all patients, even those whose PSR worsened, improved over the course of treatment. Conclusions: Elimination of six items from the anorexia/cachexia subscale of the FAACT was accomplished without loss of internal consistency or sensitivity to change in performance status. The A/CS-12 subscale provides unique, important information not captured by a generic chronic illness questionnaire.

  • The Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI): a brief assessment of patients' subjective response to treatment for anorexia/cachexia
    Quality of Life Research, 1995
    Co-Authors: David Cella, J. Vonroenn, Stephen Lloyd, H. P. Browder
    Abstract:

    A brief visual analogue instrument was developed and tested in the context of a multicentre randomized double-blinded four-dose trial of megestrol acetate for the treatment of AIDS-related anorexia/cachexia. This nine-item instrument, the Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI), was administered every 4 weeks after initiation of study drug (placebovs 100 mg, 400 mg or 800 mg of drug). The purpose of the instrument was to quantify patient perception of benefit in areas such as decreased concern over weight, decreased concern over appearance, increased pleasure in eating and increase in global perception of quality of life. Post-trial psychometric evaluation of the instrument strongly supported the use of a seven-item index of subjective recovery from symptoms of anorexia/cachexia (BACRI-7) and a single criterion item depicting patient perception of benefit (BACRI-1). The BACRI-7 and BACRI-1 scales showed significant improvement over 12 weeks in patients who received higher dose active drug (400 and 800 mg) compared with the placebo and 100 mg doses. Further differentiation of 400vs 800 mg arms was seen in the BACRI-7 results, consistent with dose-response improvements in weight and lean body mass changes. Quadratic trends over time in lean body mass change and provider-rated appetite grade suggested peak therapeutic effect at 8 weeks for these endpoints, whereas the absence of these trends in overall weight and patient-reported BACRI scores suggested that these benefits are more persistent. Although subjective (patient-reported) benefit is strongly associated with objective indicators of improvement, there remains the possibility that there is some added, independent benefit of megestrol acetate to subjective well-being.

  • The Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI)
    1995
    Co-Authors: David Cella, J. Vonroenn, Stephen Lloyd, H. P. Browder
    Abstract:

    Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) questionnaire created to evaluate patient’s perceptions regarding benefit of treatment for Anorexia/Cashexia syndrome. BACRI questionnaire assess the overall impact of medical interventions on health related quality of life indicators such as, significant impact on health, extent of change in appearance, comments from persons close to patients on how they feel about their appearance, change in appetite, feeling better or worse overall, and better or worse quality of life. The questionnaire includes 9 items rated on a visual analogue scale. Participants are asked to specify their level of agreement to the item by indicating a position along a continuous line between two end-points. The midpoint on the line between two end-points represents a neutral well being where changes not occur.

David A. Brown - One of the best experts on this subject based on the ideXlab platform.

  • Targeting the divergent TGFβ superfamily cytokine MIC-1/GDF15 for therapy of anorexia/cachexia syndromes
    Current Opinion in Supportive and Palliative Care, 2018
    Co-Authors: Vicky Wang-wei Tsai, David A. Brown, Samuel N. Breit
    Abstract:

    Purpose of reviewTo review recent finding on MIC-1/GDF15 and re-evaluate it as a potential target for the therapy of anorexia/cachexia syndromes.Recent findingsMIC-1/GDF15 consistently induces anorexia/cachexia in animal models. Its actions on brainstem feeding centers leads to anorexia, inducing pr

  • Anorexia-Cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15.
    International Journal of Obesity, 2015
    Co-Authors: Vicky Wang-wei Tsai, David A. Brown, A Salis, Samuel N. Breit
    Abstract:

    Anorexia–cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15

  • Anorexia/cachexia of chronic diseases: a role for the TGF-β family cytokine MIC-1/GDF15
    Journal of Cachexia Sarcopenia and Muscle, 2012
    Co-Authors: Vicky W. W. Tsai, David A. Brown, Yasmin Husaini, Rakesh Manandhar, Hong Ping Zhang, Kate Harriott, Lele Jiang, Amanda Sainsbury, Samuel N. Breit
    Abstract:

    Anorexia/cachexia is a common and currently mostly untreatable complication of advanced cancer. It is also a feature of a number of chronic diseases and can also occur as part of the normal ageing process. Over recent years, two different, but sometimes overlapping, processes have been identified to mediate anorexia/cachexia: those that act primarily on muscle reducing its mass and function, and processes that decrease nutrition leading to loss of both fat and muscle. In the case of at least some cancers, the latter process is sometimes driven by marked overexpression of macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15). MIC-1/GDF15 is a transforming growth factor beta (TGF-β) family cytokine that is found in the serum of all normal individuals at an average concentration of about 0.6 ng/ml. Its increased expression in both cancers and other diseases can result in 10–100-fold or more elevation of its serum levels. In experimental animals, serum MIC-1/GDF15 levels at the lower end of this range induce anorexia by direct actions of the circulating cytokine on feeding centres in the brain. Mice with tumours overexpressing MIC-1/GDF15 display decreased food intake, loss of lean and fat mass and cachexia. That this process also mediates anorexia/cachexia in humans is suggested by the fact that there is a direct correlation between the degree of serum MIC-1/GDF15 elevation and the amount of cancer-related weight loss, the first such relationship demonstrated. Further, in experimental animals, weight loss can be reversed by neutralisation of tumour-produced MIC-1/GDF15 with a specific monoclonal antibody, suggesting the possibility of effective therapy of patients with the devastating complication of anorexia/cachexia.

A Salis - One of the best experts on this subject based on the ideXlab platform.

  • Anorexia–cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15
    International Journal of Obesity, 2016
    Co-Authors: V W W Tsai, D A Brown, A Salis, S N Breit
    Abstract:

    Anorexia–cachexia associated with cancer and other diseases is a common and often fatal condition representing a large area of unmet medical need. It occurs most commonly in advanced cancer and is probably a consequence of molecules released by tumour cells, or tumour-associated interstitial or immune cells. These may then act directly on muscle to cause atrophy and/or may cause anorexia, which then leads to loss of both fat and lean mass. Although the aetiological triggers for this syndrome are not well characterized, recent data suggest that MIC-1/GDF15, a transforming growth factor-beta superfamily cytokine produced in large amounts by cancer cells and as a part of other disease processes, may be an important trigger. This cytokine acts on feeding centres in the hypothalamus and brainstem to cause anorexia leading to loss of lean and fat mass and eventually cachexia. In animal studies, the circulating concentrations of MIC-1/GDF15 required to cause this syndrome are similar to those seen in patients with advanced cancer, and at least some epidemiological studies support an association between MIC-1/GDF15 serum levels and measures of nutrition. This article will discuss its mechanisms of central appetite regulation, and the available data linking this action to anorexia–cachexia syndromes that suggest it is a potential target for therapy of cancer anorexia–cachexia and conversely may also be useful for the treatment of severe obesity.

  • Anorexia-Cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15.
    International Journal of Obesity, 2015
    Co-Authors: Vicky Wang-wei Tsai, David A. Brown, A Salis, Samuel N. Breit
    Abstract:

    Anorexia–cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15