WorldWideScience

Sample records for cachexia

  1. Cachexia.

    Science.gov (United States)

    Graul, A I; Stringer, M; Sorbera, L

    2016-09-01

    Cachexia is a multiorgan, multifactorial and often irreversible wasting syndrome associated with cancer and other serious, chronic illnesses including AIDS, chronic heart failure, chronic kidney disease and chronic obstructive pulmonary disease. Treatment of the patient with cachexia is currently targeted to correcting the two underlying features of the condition: anorexia and metabolic disturbances. Greater understanding of the mechanisms behind cachexia and muscle wasting have led to new therapeutic possibilities, however. Several classes of drugs are under active development for cachexia including drugs acting on hormone receptors or cytokine receptors, myostatin/activin pathway antagonists, beta-adrenoceptor agonists and cannabinoids. This review will cover the pathophysiology, epidemiology, diagnosis, treatment, drug candidates under active development and targets for therapeutic intervention of cachexia. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

  2. Cancer cachexia

    Directory of Open Access Journals (Sweden)

    Nada Rotovnik Kozjek

    2013-02-01

    Full Text Available The present article presents the Slovenian multidisciplinary agreement statement on the definition, staging, clinical classification and multimodal approach to the treatment of cachexia in cancer patients. The consensus was reached during a multidisciplinary plenary session, and is based on the international definition of cancer cachexia adopted in 2011. Cancer cachexia is a multifactorial metabolic syndrome defined by an ongoing loss of skeletal muscle with or without concomitant loss of fat, which cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterized by a negative energy and protein balance due to a variable combination of reduced food intake and metabolic changes. In cancer patients, the cachexia syndrome can develop progressively through various stages – from precachexia to cachexia and finally, to refractory cachexia–represent-ing a continuum of metabolic changes, clini-cal signs and symptoms. Patients can progress from precachexia to cachexia, and reverse from cachexia into precachectic stages, while (as the term itself implies, the condition of refractory or irreversible cachexia has poor therapeutic response. A clinical algorithm for recognition and treatment of cachexia in cancer patients is presented. All cancer patients should be screened for cachexia and precachexia on presentation. Patients who fulfil diagnostic criteria for cancer cachexia should have its clinical stage determined. According to phenotype / clinical stage, a multimodal approach should be adopted in the treatment of all cases of cancer cachexia. A typical multimodal management plan in cachectic patients consists of early dietary intervention, exercise, anti-inflammatory therapy and early cancer-related symptom relief. The cachexia treatment pathway should be adopted as a pathway parallel to conventional cancer treatment. Practical implementation of cancer cachexia

  3. Biomarkers of cancer cachexia.

    Science.gov (United States)

    Loumaye, Audrey; Thissen, Jean-Paul

    2017-12-01

    Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients. However, early diagnosis of cancer cachexia is currently limited for several reasons. Indeed, cachexia development is variable according to tumor and host characteristics. In addition, safe, accessible and non-invasive tools to detect skeletal muscle atrophy are desperately lacking in clinical practice. Finally, the precise molecular mechanisms and the key players involved in cancer cachexia remain poorly characterized. The need for an early diagnosis of cancer cachexia supports therefore the quest for a biomarker that might reflect skeletal muscle atrophy process. Current research offers different promising ways to identify such a biomarker. Initially, the quest for a biomarker of cancer cachexia has mostly focused on mediators of muscle atrophy, produced by both tumor and host, in an attempt to define new therapeutic approaches. In another hand, molecules released by the muscle into the circulation during the atrophy process have been also considered as potential biomarkers. More recently, several "omics" studies are emerging to identify new muscular or circulating markers of cancer cachexia. Some genetic markers could also contribute to identify patients more susceptible to develop cachexia. This article reviews our current knowledge regarding potential biomarkers of cancer cachexia. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  4. Animal models of cardiac cachexia.

    Science.gov (United States)

    Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

    2016-09-15

    Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Beneficial bacteria inhibit cachexia

    Science.gov (United States)

    Varian, Bernard J.; Goureshetti, Sravya; Poutahidis, Theofilos; Lakritz, Jessica R.; Levkovich, Tatiana; Kwok, Caitlin; Teliousis, Konstantinos; Ibrahim, Yassin M.; Mirabal, Sheyla; Erdman, Susan E.

    2016-01-01

    Muscle wasting, known as cachexia, is a debilitating condition associated with chronic inflammation such as during cancer. Beneficial microbes have been shown to optimize systemic inflammatory tone during good health; however, interactions between microbes and host immunity in the context of cachexia are incompletely understood. Here we use mouse models to test roles for bacteria in muscle wasting syndromes. We find that feeding of a human commensal microbe, Lactobacillus reuteri, to mice is sufficient to lower systemic indices of inflammation and inhibit cachexia. Further, the microbial muscle-building phenomenon extends to normal aging as wild type animals exhibited increased growth hormone levels and up-regulation of transcription factor Forkhead Box N1 [FoxN1] associated with thymus gland retention and longevity. Interestingly, mice with a defective FoxN1 gene (athymic nude) fail to inhibit sarcopenia after L. reuteri therapy, indicating a FoxN1-mediated mechanism. In conclusion, symbiotic bacteria may serve to stimulate FoxN1 and thymic functions that regulate inflammation, offering possible alternatives for cachexia prevention and novel insights into roles for microbiota in mammalian ontogeny and phylogeny. PMID:26933816

  6. Beneficial bacteria inhibit cachexia.

    Science.gov (United States)

    Varian, Bernard J; Goureshetti, Sravya; Poutahidis, Theofilos; Lakritz, Jessica R; Levkovich, Tatiana; Kwok, Caitlin; Teliousis, Konstantinos; Ibrahim, Yassin M; Mirabal, Sheyla; Erdman, Susan E

    2016-03-15

    Muscle wasting, known as cachexia, is a debilitating condition associated with chronic inflammation such as during cancer. Beneficial microbes have been shown to optimize systemic inflammatory tone during good health; however, interactions between microbes and host immunity in the context of cachexia are incompletely understood. Here we use mouse models to test roles for bacteria in muscle wasting syndromes. We find that feeding of a human commensal microbe, Lactobacillus reuteri, to mice is sufficient to lower systemic indices of inflammation and inhibit cachexia. Further, the microbial muscle-building phenomenon extends to normal aging as wild type animals exhibited increased growth hormone levels and up-regulation of transcription factor Forkhead Box N1 [FoxN1] associated with thymus gland retention and longevity. Interestingly, mice with a defective FoxN1 gene (athymic nude) fail to inhibit sarcopenia after L. reuteri therapy, indicating a FoxN1-mediated mechanism. In conclusion, symbiotic bacteria may serve to stimulate FoxN1 and thymic functions that regulate inflammation, offering possible alternatives for cachexia prevention and novel insights into roles for microbiota in mammalian ontogeny and phylogeny.

  7. Cachexia among US cancer patients.

    Science.gov (United States)

    Arthur, Susan T; Van Doren, Bryce A; Roy, Debosree; Noone, Joshua M; Zacherle, Emily; Blanchette, Christopher M

    2016-09-01

    Cancer cachexia is a debilitating condition and results in poor prognosis. The purpose of this study was to assess hospitalization incidence, patient characteristics, and medical cost and burden of cancer cachexia in the US. This study used a cross-sectional analysis of the Nationwide Inpatient Sample (NIS) for 2009. Five cancers reported to have the highest cachexia incidence were assessed. The hospitalization incidence related to cachexia was estimated by cancer type, cost and length of stay were compared, and descriptive statistics were reported for each cancer type, as well as differences being compared between patients with and without cachexia. Risk of inpatient death was higher for patients with cachexia in lung cancer (OR = 1.32; CI = 1.20-1.46) and in all cancers combined (OR = 1.76; CI = 1.67-1.85). The presence of cachexia increased length of stay in lung (IRR = 1.05; CI = 1.03-1.08), Kaposi's sarcoma (IRR = 1.47; CI = 1.14-1.89) and all cancers combined (IRR = 1.09; CI = 1.08-1.10). Additionally, cachectic patients in the composite category had a longer hospitalization stay compared to non-cachectic patients (3-9 days for those with cachexia and 2-7 days for those without cachexia). The cost of inpatient stay was significantly higher in cachexic than non-cachexic lung cancer patients ($13,560 vs $13 190; p Cachexia increases hospitalization costs and length of stay in several cancer types. Identifying the medical burden associated with cancer cachexia will assist in developing an international consensus for recognition and coding by the medical community and ultimately an effective treatment plans for cancer cachexia.

  8. Cancer Cachexia: Beyond Weight Loss.

    Science.gov (United States)

    Bruggeman, Andrew R; Kamal, Arif H; LeBlanc, Thomas W; Ma, Joseph D; Baracos, Vickie E; Roeland, Eric J

    2016-11-01

    Cancer cachexia is a multifactorial syndrome characterized by skeletal muscle loss leading to progressive functional impairment. Despite the ubiquity of cachexia in clinical practice, prevention, early identification, and intervention remain challenging. The impact of cancer cachexia on quality of life, treatment-related toxicity, physical function, and mortality are well established; however, establishing a clinically meaningful definition has proven challenging because of the focus on weight loss alone. Attempts to more comprehensively define cachexia through body composition, physical functioning, and molecular biomarkers, while promising, are yet to be routinely incorporated into clinical practice. Pharmacologic agents that have not been approved by the US Food and Drug Administration but that are currently used in cancer cachexia (ie, megestrol, dronabinol) may improve weight but not outcomes of interest such as muscle mass, physical activity, or mortality. Their routine use is limited by adverse effects. For the practicing oncologist, early identification and management of cachexia is critical. Oncologists must recognize cachexia beyond weight loss alone, focusing instead on body composition and physical functioning. In fact, becoming emaciated is a late sign of cachexia that characterizes its refractory stage. Given that cachexia is a multifactorial syndrome, it requires early identification and polymodal intervention, including optimal cancer therapy, symptom management, nutrition, exercise, and psychosocial support. Consequently, oncologists have a role in ensuring that these resources are available to their patients. In addition, in light of the promising investigational agents, it remains imperative to refer patients with cachexia to clinical trials so that available options can be expanded to effectively treat this pervasive problem.

  9. Cancer cachexia, mechanism and treatment

    Science.gov (United States)

    Aoyagi, Tomoyoshi; Terracina, Krista P; Raza, Ali; Matsubara, Hisahiro; Takabe, Kazuaki

    2015-01-01

    It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responses to chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials. PMID:25897346

  10. Animal models for cancer cachexia.

    Science.gov (United States)

    Ballarò, Riccardo; Costelli, Paola; Penna, Fabio

    2016-12-01

    Cancer cachexia is a frequent syndrome that affects patient quality of life, anticancer treatment effectiveness, and overall survival. The lack of anticancer cachexia therapies likely relies on the complexity of the syndrome that renders difficult to design appropriate clinical trials and, conversely, on the insufficient knowledge of the underlying pathogenetic mechanisms. The aim of this review is to collect the most relevant latest information regarding cancer cachexia with a special focus on the experimental systems adopted for modeling the disease in translational studies. The scenario of preclinical models for the study of cancer cachexia is not static and is rapidly evolving in parallel with new prospective treatment options. The well established syngeneic models using rodent cancer cells injected ectopically are now used alongside new ones featuring orthotopic injection, human cancer cell or patient-derived xenograft, or spontaneous tumors in genetically engineered mice. The use of more complex animal models that better resemble cancer cachexia, ideally including also the administration of chemotherapy, will expand the understanding of the underlying mechanisms and will allow a more reliable evaluation of prospective drugs for translational purposes.

  11. Treatment of cachexia in oncology

    Directory of Open Access Journals (Sweden)

    E M Tazi

    2010-01-01

    Full Text Available Background: Cachexia is a complex metabolic syndrome associated with many chronic or end-stage diseases, especially cancer, and is characterized by loss of muscle with or without loss of fat mass. The management of cachexia is a complex challenge that should address the different causes underlying this clinical event with an integrated or multimodal treatment approach targeting the different factors involved in its pathophysiology. Aims and Objectives : The purpose of this article was to review the current medical treatment of cancer-related cachexia, in particular focusing on combination therapy and ongoing research. Results : Among the treatments proposed in the literature for cancer-related cachexia, some proved to be ineffective, namely, cyproheptadine, hydrazine, metoclopramide, and pentoxifylline. Among effective treatments, progestagens are currently considered the best available treatment option for cancer-related cachexia, and they are the only drugs approved in Europe. Drugs with a strong rationale that have failed or have not shown univocal results in clinical trials so far include eicosapentaenoic acid, cannabinoids, bortezomib, and anti-TNF-alpha MoAb. Several emerging drugs have shown promising results but are still under clinical investigation (thalidomide, selective cox-2 inhibitors, ghrelin mimetics, insulin, oxandrolone, and olanzapine. Conclusions : To date, despite several years of coordinated efforts in basic and clinical research, practice guidelines for the prevention and treatment of cancer-related muscle wasting are lacking, mainly because of the multifactorial pathogenesis of the syndrome. From all the data presented, one can speculate that one single therapy may not be completely successful in the treatment of cachexia. From this point of view, treatments involving different combinations are more likely to be successful.

  12. [Cancer cachexia and white adipose tissue browning].

    Science.gov (United States)

    Zhang, S T; Yang, H M

    2016-08-01

    Cancer cachexia occurs in a majority of advanced cancer patients. These patients with impaired physical function are unable to tolerance cancer treatment well and have a significantly reduced survival rate. Currently, there is no effective clinical treatment available for cancer cachexia, therefore, it is necessary to clarify the molecular mechanisms of cancer cachexia, moreover, new therapeutic targets for cancer cachexia treatment are urgently needed. Very recent studies suggest that, during cancer cachexia, white adipose tissue undergo a 'browning' process, resulting in increased lipid mobilization and energy expenditure, which may be necessary for the occurrence of cancer cachexia. In this article, we summarize the definition and characteristics of cancer cachexia and adipose tissue 'browning', then, we discuss the new study directions presented in latest research.

  13. Clinical results in cachexia therapeutics.

    Science.gov (United States)

    Crawford, Jeffrey

    2016-05-01

    This article highlights recent developments in the area of cancer cachexia and therapeutic interventions. Therapeutic interventions in cancer cachexia have been guided by clinical studies focused on the central role of muscle and the increased use of CT imaging to measure the impact of skeletal muscle loss on clinical outcomes. At the translational level, a number of different model systems have emphasized the importance of blockade of tumor-induced inflammation and its potential impact on reversing the cachexia phenotype, including FN14, a receptor in the TNF pathway, as well as the parathyroid hormone-related protein. Clinical studies continue to demonstrate the importance of nutrition and exercise as part of a multimodality approach. Although a number of promising agents are being evaluated, both enobosarm, a selected androgen receptor modulator, and anamorelin, a ghrelin agonist have completed phase III trials. Both agents have shown significant impact on reversal of skeletal muscle loss, but inconsistent effect on physical function improvement. Anamorelin also has a positive effect on appetite and weight gain. Further analysis of these studies, along with regulatory guidance, will be critical in the further development of these and other promising agents in the clinical management of patients with cancer cachexia.

  14. Cancer cachexia, recent advances, and future directions.

    Science.gov (United States)

    Penet, Marie-France; Bhujwalla, Zaver M

    2015-01-01

    Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass with or without loss of fat mass. The syndrome cannot be fully reversed by conventional nutritional support, and despite an increased number of studies related to cancer cachexia, the underlying mechanisms are still poorly defined, and therapeutic options are limited. This review focuses on recent studies investigating mechanisms and pathways in cancer cachexia. The role of molecular and functional imaging in identifying cachexia at an earlier stage, in identifying potential metabolic targets and pathways, and in assessing treatment efficacy is also reviewed.

  15. Cancer Cachexia, Recent Advances, and Future Directions

    Science.gov (United States)

    Penet, Marie-France; Bhujwalla, Zaver M.

    2016-01-01

    Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass with or without loss of fat mass. The syndrome cannot be fully reversed by conventional nutritional support, and despite an increased number of studies related to cancer cachexia, the underlying mechanisms are still poorly defined and therapeutic options are limited. This review focuses on recent studies investigating mechanisms and pathways in cancer cachexia. The role of molecular and functional imaging in identifying cachexia at an earlier stage, in identifying potential metabolic targets and pathways, and in assessing treatment efficacy is also reviewed. PMID:25815852

  16. Cachexia: clinical features when inflammation drives malnutrition.

    Science.gov (United States)

    Laviano, Alessandro; Koverech, Angela; Mari, Alessia

    2015-11-01

    Cachexia is a clinically relevant syndrome which impacts on quality of life, morbidity and mortality of patients suffering from acute and chronic diseases. The hallmark of cachexia is muscle loss, which is triggered by disease-associated inflammatory response. Cachexia is a continuum and therefore a staging system is needed. Initially, a three-stage system (i.e. pre-cachexia, cachexia and refractory cachexia) was proposed. More recent evidence supports the use of a five-stage classification system, based on patient's BMI and severity of weight loss, to better predict clinical outcome. Also, large clinical trials in cancer patients demonstrated that cachexia emerging during chemotherapy has greater influence on survival than weight loss at baseline. Therefore, becoming widely accepted is the importance of routinely monitoring patients' nutritional status to detect early changes and diagnose cachexia in its early phases. Although cachexia is associated with the presence of anabolic resistance, it has been shown that sustained yet physiological hyperaminoacidaemia, as well as the use of specific nutrients, is able to overcome impaired protein synthesis and revert catabolism. More importantly, clinical evidence demonstrates that preservation of nutritional status during chemotherapy or improvement of body weight after weight loss is associated with longer survival in cancer patients.

  17. Cardiac cachexia: hic et nunc

    Science.gov (United States)

    Loncar, Goran; Springer, Jochen; Anker, Markus; Doehner, Wolfram

    2016-01-01

    Abstract Cardiac cachexia (CC) is the clinical entity at the end of the chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely, the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. A better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia, and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF. PMID:27386168

  18. Liver and muscle protein metabolism in cachexia

    NARCIS (Netherlands)

    Peters, J.A.C.

    2009-01-01

    Up to 50% of cancer patients suffer from progressive weight loss (cachexia). Cachexia is induced by proinflammatory mediators (cytokines), induced by the tumor’s presence. These cytokines induce so-called acute phase protein synthesis by the liver, followed by skeletal muscle protein breakdown.

  19. Cancer Cachexia and MicroRNAs

    Directory of Open Access Journals (Sweden)

    Rodolfo Gonzalez Camargo

    2015-01-01

    Full Text Available Cancer cachexia is a paraneoplastic syndrome compromising quality of life and survival, mainly characterized by involuntary weight loss, fatigue, and systemic inflammation. The syndrome is described as a result of tumor-host interactions characterized by an inflammatory response by the host to the presence of the tumor. Indeed, systemic inflammation is considered a pivotal feature in cachexia progression and maintenance. Cytokines are intimately related to chronic systemic inflammation and the mechanisms underlying the release of these factors are not totally elucidated, the etiology of cachexia being still not fully understood. Therefore, the understanding of cachexia-related mechanisms, as well as the establishment of markers for the syndrome, is very relevant. MicroRNAs (miRNAs are a class of noncoding RNAs interfering with gene regulation. Different miRNA expression profiles are associated with different diseases and inflammatory processes. miRNAs modulate adipose and skeletal muscle tissue metabolism in cancer cachexia and also tumor and tissue derived inflammation. Therefore, we propose a possible role for miRNAs in the modulation of the host inflammatory response during cachexia. Moreover, the establishment of a robust body of evidence in regard to miRNAs and the mechanisms underlying cachexia is mandatory, and shall contribute to the improvement of its diagnosis and treatment.

  20. Cardiac Cachexia: Perspectives for Prevention and Treatment.

    Science.gov (United States)

    Okoshi, Marina Politi; Capalbo, Rafael Verardino; Romeiro, Fernando G; Okoshi, Katashi

    2017-01-01

    Cachexia is a prevalent pathological condition associated with chronic heart failure. Its occurrence predicts increased morbidity and mortality independent of important clinical variables such as age, ventricular function, or heart failure functional class. The clinical consequences of cachexia are dependent on both weight loss and systemic inflammation, which accompany cachexia development. Skeletal muscle wasting is an important component of cachexia; it often precedes cachexia development and predicts poor outcome in heart failure. Cachexia clinically affects several organs and systems. It is a multifactorial condition where underlying pathophysiological mechanisms are not completely understood making it difficult to develop specific prevention and treatment therapies. Preventive strategies have largely focused on muscle mass preservation. Different treatment options have been described, mostly in small clinical studies or experimental settings. These include nutritional support, neurohormonal blockade, reducing intestinal bacterial translocation, anemia and iron deficiency treatment, appetite stimulants, immunomodulatory agents, anabolic hormones, and physical exercise regimens. Currently, nonpharmacological therapy such as nutritional support and physical exercise are considered central to cachexia prevention and treatment.

  1. Highlights from the 9th Cachexia Conference.

    Science.gov (United States)

    Ebner, Nicole; von Haehling, Stephan

    2017-06-01

    This article highlights updates of pathways as well as pre-clinical and clinical studies into the field of wasting disorders that were presented at the 9th Cachexia Conference held in Berlin, Germany, December 2016. This year, some interesting results from clinical trials and different new therapeutic targets were shown. This article presents the biological and clinical significance of different markers and new diagnostic tools and cut-offs of detecting skeletal muscle wasting. Effective treatments of cachexia and wasting disorders are urgently needed in order to improve the patients' quality of life and their survival. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  2. Omics/systems biology and cancer cachexia.

    Science.gov (United States)

    Gallagher, Iain J; Jacobi, Carsten; Tardif, Nicolas; Rooyackers, Olav; Fearon, Kenneth

    2016-06-01

    Cancer cachexia is a complex syndrome generated by interaction between the host and tumour cells with a background of treatment effects and toxicity. The complexity of the physiological pathways likely involved in cancer cachexia necessitates a holistic view of the relevant biology. Emergent properties are characteristic of complex systems with the result that the end result is more than the sum of its parts. Recognition of the importance of emergent properties in biology led to the concept of systems biology wherein a holistic approach is taken to the biology at hand. Systems biology approaches will therefore play an important role in work to uncover key mechanisms with therapeutic potential in cancer cachexia. The 'omics' technologies provide a global view of biological systems. Genomics, transcriptomics, proteomics, lipidomics and metabolomics approaches all have application in the study of cancer cachexia to generate systems level models of the behaviour of this syndrome. The current work reviews recent applications of these technologies to muscle atrophy in general and cancer cachexia in particular with a view to progress towards integration of these approaches to better understand the pathology and potential treatment pathways in cancer cachexia. Copyright © 2016. Published by Elsevier Ltd.

  3. Relevance of the new pre-cachexia and cachexia definitions for patients with rheumatoid arthritis

    NARCIS (Netherlands)

    van Bokhorst-de van der Schueren, M.A.E.; Konijn, N.P.C.; Bultink, I.E.M.; Lems, W.F.; Earthman, C.P.; van Tuyl, H.D.

    2012-01-01

    Background & aims: The recently proposed definitions of 'pre-cachexia' and 'cachexia' might offer new possibilities for the detection of malnutrition in patients with rheumatoid arthritis (RA). Methods: The prevalence of different components of nutritional status and the compiled definitions of

  4. Genetic basis of interindividual susceptibility to cancer cachexia ...

    Indian Academy of Sciences (India)

    Abstract. Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of bio- logical processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications ...

  5. Genetic basis of interindividual susceptibility to cancer cachexia ...

    Indian Academy of Sciences (India)

    Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological ...

  6. STAT3 in the systemic inflammation of cancer cachexia.

    Science.gov (United States)

    Zimmers, Teresa A; Fishel, Melissa L; Bonetto, Andrea

    2016-06-01

    Weight loss is diagnostic of cachexia, a debilitating syndrome contributing mightily to morbidity and mortality in cancer. Most research has probed mechanisms leading to muscle atrophy and adipose wasting in cachexia; however cachexia is a truly systemic phenomenon. Presence of the tumor elicits an inflammatory response and profound metabolic derangements involving not only muscle and fat, but also the hypothalamus, liver, heart, blood, spleen and likely other organs. This global response is orchestrated in part through circulating cytokines that rise in conditions of cachexia. Exogenous Interleukin-6 (IL6) and related cytokines can induce most cachexia symptomatology, including muscle and fat wasting, the acute phase response and anemia, while IL-6 inhibition reduces muscle loss in cancer. Although mechanistic studies are ongoing, certain of these cachexia phenotypes have been causally linked to the cytokine-activated transcription factor, STAT3, including skeletal muscle wasting, cardiac dysfunction and hypothalamic inflammation. Correlative studies implicate STAT3 in fat wasting and the acute phase response in cancer cachexia. Parallel data in non-cancer models and disease states suggest both pathological and protective functions for STAT3 in other organs during cachexia. STAT3 also contributes to cancer cachexia through enhancing tumorigenesis, metastasis and immune suppression, particularly in tumors associated with high prevalence of cachexia. This review examines the evidence linking STAT3 to multi-organ manifestations of cachexia and the potential and perils for targeting STAT3 to reduce cachexia and prolong survival in cancer patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Biomarkers for cardiac cachexia: reality or utopia.

    Science.gov (United States)

    Martins, Telma; Vitorino, Rui; Amado, Francisco; Duarte, José Alberto; Ferreira, Rita

    2014-09-25

    Cardiac cachexia is a serious complication of chronic heart failure, characterized by significant weight loss and body wasting. Chronic heart failure-related muscle wasting results from a chronic imbalance in the activation of anabolic or catabolic pathways, caused by a series of immunological, metabolic, and neurohormonal processes. In spite of the high morbidity and mortality associated to this condition, there is no universally accepted definition or specific biomarkers for cardiac cachexia, which makes its diagnosis and treatment difficult. Several hormonal, inflammatory and oxidative stress molecules have been proposed as serological markers of prognosis in cardiac cachexia but with doubtful success. As individual biomarkers may have limited sensitivity and specificity, multimarker strategies involving mediators of the biological processes modulated by cardiac cachexia will strongly contribute for the diagnosis and management of the disease, as well as for the establishment of new therapeutic targets. An integrated analysis of the biomarkers proposed so far for cardiac cachexia is made in the present review, highlighting the biological processes to which they are related. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Practical multimodal care for cancer cachexia.

    Science.gov (United States)

    Maddocks, Matthew; Hopkinson, Jane; Conibear, John; Reeves, Annie; Shaw, Clare; Fearon, Ken C H

    2016-12-01

    Cancer cachexia is common and reduces function, treatment tolerability and quality of life. Given its multifaceted pathophysiology a multimodal approach to cachexia management is advocated for, but can be difficult to realise in practice. We use a case-based approach to highlight practical approaches to the multimodal management of cachexia for patients across the cancer trajectory. Four cases with lung cancer spanning surgical resection, radical chemoradiotherapy, palliative chemotherapy and no anticancer treatment are presented. We propose multimodal care approaches that incorporate nutritional support, exercise, and anti-inflammatory agents, on a background of personalized oncology care and family-centred education. Collectively, the cases reveal that multimodal care is part of everyone's remit, often focuses on supported self-management, and demands buy-in from the patient and their family. Once operationalized, multimodal care approaches can be tested pragmatically, including alongside emerging pharmacological cachexia treatments. We demonstrate that multimodal care for cancer cachexia can be achieved using simple treatments and without a dedicated team of specialists. The sharing of advice between health professionals can help build collective confidence and expertise, moving towards a position in which every team member feels they can contribute towards multimodal care.

  9. Identification of neutrophil-derived proteases and angiotensin II as biomarkers of cancer cachexia.

    Science.gov (United States)

    Penafuerte, Claudia A; Gagnon, Bruno; Sirois, Jacinthe; Murphy, Jessica; MacDonald, Neil; Tremblay, Michel L

    2016-03-15

    Cachexia is a metabolic disorder characterised by muscle wasting, diminished response to anti-cancer treatments and poor quality of life. Our objective was to identify blood-based biomarkers of cachexia in advanced cancer patients. Hence, we characterised the plasma cytokine and blood cell mRNA profiles of patients grouped in three cohorts: patients with cachexia, pre-cachexia (no cachexia but high CRP levels: ⩾ 5 mg l⁻¹) and no cachexia (no cachexia and CRP: cachexia. These findings contribute to early diagnosis and prevention of cachexia.

  10. Cachexia and wasting: a modern approach

    National Research Council Canada - National Science Library

    Mantovani, Giovanni; Anker, Stefan D

    2006-01-01

    ... consequences of prolonged immunological and hormonal challenges due to both the illness process itself and the aggressive therapies. This book aims to conceptualise the fact that cachexia is a clinical syndrome that accompanies the course of several medical conditions such as cancer, heart failure, diabetes, chronic renal failure and chronic obstr...

  11. Cachexia in patients with oesophageal cancer.

    Science.gov (United States)

    Anandavadivelan, Poorna; Lagergren, Pernilla

    2016-03-01

    Oesophageal cancer is a debilitating disease with a poor prognosis, and weight loss owing to malnutrition prevails in the majority of patients. Cachexia, a multifactorial syndrome characterized by the loss of fat and skeletal muscle mass and systemic inflammation arising from complex host-tumour interactions is a major contributor to malnutrition, which is a determinant of tolerance to treatment and survival. In patients with oesophageal cancer, cachexia is further compounded by eating difficulties owing to the stage and location of the tumour, and the effects of neoadjuvant therapy. Treatment with curative intent involves exceptionally extensive and invasive surgery, and the subsequent anatomical changes often lead to eating difficulties and severe postoperative malnutrition. Thus, screening for cachexia by means of percentage weight loss and BMI during the cancer trajectory and survivorship periods is imperative. Additionally, markers of inflammation (such as C-reactive protein), dysphagia and appetite loss should be assessed at diagnosis. Routine assessments of body composition are also necessary in patients with oesophageal cancer to enable assessment of skeletal muscle loss, which might be masked by sarcopenic obesity in these patients. A need exists for clinical trials examining the effectiveness of therapeutic and physical-activity-based interventions in mitigating muscle loss and counteracting cachexia in these patients.

  12. Developing models for cachexia and their implications in drug discovery.

    Science.gov (United States)

    Konishi, Masaaki; Ebner, Nicole; von Haehling, Stephan; Anker, Stefan D; Springer, Jochen

    2015-07-01

    Cachexia is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass. Systemic inflammation plays a central role in its pathophysiology. As millions of patients are in a cachectic state of chronic disease, cachexia is one of the major causes of death worldwide. Difficulties in the recruitment and follow-up of clinical trials mean that well-characterized animal models are of great importance in developing cachexia therapies. However, some of the widely used animal models have limitations in procedural reproducibility or in recapitulating in the cachectic phenotype, which has warranted the development of novel models for cachexia. This review focuses on some of the currently developing rodent models designed to mimic each co-morbidity in cachexia. Through developing cancer models, researchers have been seeking more targets for intervention. In cardiac cachexia, technical issues have been overcome by transgenic models. Furthermore, the development of new animal models has enabled the elucidation of the roles of inflammation, anabolism/catabolism in muscle/fat tissue and anorexia on cachexia. As metabolic and inflammatory pathways in cachexia may compromise cardiac muscle, the analysis of cardiac function/tissue in non-cardiac cachexia may be a useful component of cachexia assessment common to different underlying diseases and pave the way for novel drug discovery.

  13. [Prevention and treatment of cachexia : Exercise and nutritional therapy].

    Science.gov (United States)

    Wilms, B; Schmid, S M; Luley, K; Wiskemann, J; Lehnert, H

    2016-10-01

    Cachexia is a multifactorial and complex syndrome characterized by progressive functional impairment and ongoing loss in quality of life, which lead to a deterioration of the prognosis for affected patients. The prevalence of cachexia can be very high and is up to 80 % in patients with malignant tumors. The aim of the study was to assess the relevance of exercise and nutrition in the prevention and therapy of cachexia. An evaluation of the current literature on exercise and nutritional therapy in patients with cachexia or with advanced stage diseases where a high prevalence of cachexia is probable, was carried out. There is a lack of scientific evidence for the benefits of exercise in cachexia. A major problem of relevant studies was that cachexia was frequently not defined according to valid criteria; however, data indicate a benefit of exercise training in patients with advanced diseases associated with a high prevalence of cachexia. A solely nutritional intervention and dietary counselling seem to be of minimal benefit. The administration of omega 3 fatty acids is controversially discussed. Although there is a lack of data on the effects of exercise and nutritional therapy in cachexia, there is evidence for the benefits. The present data indicate the necessity for the use of a multimodal treatment including exercise, nutritional and pharmacological therapy in cachexia. There is a great necessity for prospective studies.

  14. Understanding cachexia as a cancer metabolism syndrome

    Science.gov (United States)

    Porporato, P E

    2016-01-01

    Metabolic reprogramming occurs in tumors to foster cancer cell proliferation, survival and metastasis, but as well at a systemic level affecting the whole organism, eventually leading to cancer cachexia. Indeed, as cancer cells rely on external sources of nitrogen and carbon skeleton to grow, systemic metabolic deregulation promoting tissue wasting and metabolites mobilization ultimately supports tumor growth. Cachectic patients experience a wide range of symptoms affecting several organ functions such as muscle, liver, brain, immune system and heart, collectively decreasing patients' quality of life and worsening their prognosis. Moreover, cachexia is estimated to be the direct cause of at least 20% of cancer deaths. The main aspect of cachexia syndrome is the unstoppable skeletal muscle and fat storage wasting, even with an adequate caloric intake, resulting in nutrient mobilization – both directly as lipid and amino acids and indirectly as glucose derived from the exploitation of liver gluconeogenesis – that reaches the tumor through the bloodstream. From a metabolic standpoint, cachectic host develops a wide range of dysfunctions, from increased insulin and IGF-1 resistance to induction of mitochondrial uncoupling proteins and fat tissue browning resulting in an increased energy expenditure and heat generation, even at rest. For a long time, cachexia has been merely considered an epiphenomenon of end-stage tumors. However, in specific tumor types, such as pancreatic cancers, it is now clear that patients present markers of tissue wasting at a stage in which tumor is not yet clinically detectable, and that host amino acid supply is required for tumor growth. Indeed, tumor cells actively promote tissue wasting by secreting specific factors such as parathyroid hormone-related protein and micro RNAs. Understanding the molecular and metabolic mediators of cachexia will not only advance therapeutic approaches against cancer, but also improve patients' quality of

  15. Exploiting the therapeutic potential of leptin signaling in cachexia.

    Science.gov (United States)

    Mak, Robert H; Cheung, Wai W; Gertler, Arieh

    2014-12-01

    The anorexia-cachexia syndrome is a complication of many chronic conditions including cancer, chronic obstructive pulmonary disease, congestive heart failure, and chronic kidney disease (CKD). Leptin levels are significantly elevated in CKD patients and are associated with markers of poor nutritional status as well as mortality and morbidity. This review will focus on the mechanism and exploit the therapeutic potential of leptin signaling in CKD-associated cachexia. Studies in db/db mice show that the lack of leptin receptor is protective against CKD-induced cachexia. Blockade of leptin's downstream mediators, such as melanocortin-4 receptor, attenuated CKD-associated cachexia. Pegylation of leptin antagonists resulted in a potent and effective long-acting reagents suitable for in-vivo studies or therapies. Pegylated leptin antagonist treatment ameliorates CKD-associated cachexia in mice. Leptin antagonism may represent a viable therapeutic strategy for cachexia in CKD.

  16. The effect of thalidomide on cachexia in upper gastrointestinal cancer

    OpenAIRE

    Green, Susi

    2015-01-01

    Progress made in the palliation of those with terminal cancers has allowed most symptoms to be controlled if not completely alleviated. For many in this situation now, the most overwhelming and unpleasant ongoing problems are related to the accompanying cachexia. Cachexia - (Greek,kakos-bad, hexis-condition) a wasting syndrome that causes weakness and a loss of weight, fat, and muscle(1) Cachexia has direct and tangible consequences such as reducing independence to a level where the pat...

  17. Diagnostic criteria for cancer cachexia: data versus dogma.

    Science.gov (United States)

    Martin, Lisa

    2016-05-01

    Cachexia limits cancer therapy, quality of life, and survival of patients with cancer. Challenges identifying and diagnosing cachexia are due to disparities in diagnostic criteria. A framework for classification of cancer cachexia was recently defined by international consensus. This review describes recent efforts to use this framework to develop definitive diagnostic criteria for cancer cachexia. The principle proposed in the cancer cachexia framework for development of diagnostic criteria is that 'definitive cutoffs for variables could be determined from large contemporary datasets by determining the values that relate optimally to meaningful patient-centered outcomes.' Clearly defined statistical methods to examine distributions of diagnostic criteria in relation to an outcome are used to achieve this task. As a first step, a dataset of more than 11 000 cancer patients from Europe and Canada was compiled, and used to develop and validate a new grading system for cancer-associated weight loss, based on a risk stratification with survival as the outcome. The next refinements for diagnostic criteria will be enabled by the emergence of rich datasets including key variables further specifying the nature of cachexia such as skeletal muscle depletion, reduced food intake, and inflammation. Development of diagnostic criteria for cancer cachexia is based on a solid conceptual foundation and is moving toward defining the type of assessments, optimal values, and combinations of criteria that best define cachexia. Large contemporary datasets representing different cancer populations, candidate cachexia diagnostic criteria, and clinical outcomes will further ensure developmental and validation efforts.

  18. Impact of cachexia on outcomes in aggressive lymphomas.

    Science.gov (United States)

    Karmali, Reem; Alrifai, Taha; Fughhi, Ibtihaj A M; Ng, Ronald; Chukkapalli, Vineela; Shah, Palmi; Basu, Sanjib; Nathan, Sunita; Szymanski-Grant, Kelly; Gordon, Leo I; Venugopal, Parameswaran; Penedo, Frank J; Borgia, Jeffrey A

    2017-06-01

    Cancer cachexia is defined as a state of involuntary weight loss, attributed to altered body composition with muscle mass loss and/or loss of adiposity. Identifying the association between cancer cachexia and outcomes may pave the way for novel agents that target the cancer cachexia process. Clinical parameters for measurement of cancer cachexia are needed. We conducted a single-institution retrospective analysis that included 86 NHL patients with the aim of identifying an association between cancer cachexia and outcomes in aggressive lymphomas using the cachexia index (CXI) suggested by Jafri et al. (Clin Med Insights Oncol 9:87-93, 15). Impact of cachexia factors on progression-free survival (PFS) and overall survival (OS) were assessed using log-rank test and Cox proportional hazards regression. Patients were dichotomized around the median CXI into "non-cachectic" (CXI ≥49.8, n = 41) and "cachectic" (CXI Cachexia as defined by the CXI is prognostic in aggressive lymphomas and implies that novel therapeutic strategies directed at reversing cachexia may improve survival in this population.

  19. Pancreatic cancer cachexia: a review of mechanisms and therapeutics

    Science.gov (United States)

    Tan, Carlyn R.; Yaffee, Patrick M.; Jamil, Laith H.; Lo, Simon K.; Nissen, Nicholas; Pandol, Stephen J.; Tuli, Richard; Hendifar, Andrew E.

    2014-01-01

    Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions. PMID:24624094

  20. Leptin in Anorexia and Cachexia Syndrome

    Directory of Open Access Journals (Sweden)

    Diana R. Engineer

    2012-01-01

    Full Text Available Leptin is a product of the obese (OB gene secreted by adipocytes in proportion to fat mass. It decreases food intake and increases energy expenditure by affecting the balance between orexigenic and anorexigenic hypothalamic pathways. Low leptin levels are responsible for the compensatory increase in appetite and body weight and decreased energy expenditure (EE following caloric deprivation. The anorexia-cachexia syndrome is a complication of many chronic conditions including cancer, chronic obstructive pulmonary disease, congestive heart failure, chronic kidney disease, and aging, where the decrease in body weight and food intake is not followed by a compensatory increase in appetite or decreased EE. Crosstalk between leptin and inflammatory signaling known to be activated in these conditions may be responsible for this paradox. This manuscript will review the evidence and potential mechanisms mediating changes in the leptin pathway in the setting of anorexia and cachexia associated with chronic diseases.

  1. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) "cachexia-anorexia in chronic wasting diseases" and "nutrition in geriatrics".

    Science.gov (United States)

    Muscaritoli, M; Anker, S D; Argilés, J; Aversa, Z; Bauer, J M; Biolo, G; Boirie, Y; Bosaeus, I; Cederholm, T; Costelli, P; Fearon, K C; Laviano, A; Maggio, M; Rossi Fanelli, F; Schneider, S M; Schols, A; Sieber, C C

    2010-04-01

    Chronic diseases as well as aging are frequently associated with deterioration of nutritional status, loss muscle mass and function (i.e. sarcopenia), impaired quality of life and increased risk for morbidity and mortality. Although simple and effective tools for the accurate screening, diagnosis and treatment of malnutrition have been developed during the recent years, its prevalence still remains disappointingly high and its impact on morbidity, mortality and quality of life clinically significant. Based on these premises, the Special Interest Group (SIG) on cachexia-anorexia in chronic wasting diseases was created within ESPEN with the aim of developing and spreading the knowledge on the basic and clinical aspects of cachexia and anorexia as well as of increasing the awareness of cachexia among health professionals and care givers. The definition, the assessment and the staging of cachexia, were identified as a priority by the SIG. This consensus paper reports the definition of cachexia, pre-cachexia and sarcopenia as well as the criteria for the differentiation between cachexia and other conditions associated with sarcopenia, which have been developed in cooperation with the ESPEN SIG on nutrition in geriatrics. Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  2. Novel targeted therapies for cancer cachexia.

    Science.gov (United States)

    Argilés, Josep M; López-Soriano, Francisco Javier; Stemmler, Britta; Busquets, Sílvia

    2017-07-27

    Anorexia and metabolic alterations are the main components of the cachectic syndrome. Glucose intolerance, fat depletion, muscle protein catabolism and other alterations are involved in the development of cancer cachexia, a multi-organ syndrome. Nutritional approach strategies are not satisfactory in reversing the cachectic syndrome. The aim of the present review is to deal with the recent therapeutic targeted approaches that have been designed to fight and counteract wasting in cancer patients. Indeed, some promising targeted therapeutic approaches include ghrelin agonists, selective androgen receptor agonists, β-blockers and antimyostatin peptides. However, a multi-targeted approach seems absolutely essential to treat patients affected by cancer cachexia. This approach should not only involve combinations of drugs but also nutrition and an adequate program of physical exercise, factors that may lead to a synergy, essential to overcome the syndrome. This may efficiently reverse the metabolic changes described above and, at the same time, ameliorate the anorexia. Defining this therapeutic combination of drugs/nutrients/exercise is an exciting project that will stimulate many scientific efforts. Other aspects that will, no doubt, be very important for successful treatment of cancer wasting will be an optimized design of future clinical trials, together with a protocol for staging cancer patients in relation to their degree of cachexia. This will permit that nutritional/metabolic/pharmacological support can be started early in the course of the disease, before severe weight loss occurs. Indeed, timing is crucial and has to be taken very seriously when applying the therapeutic approach. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  3. Fn14: a new player in cancer-induced cachexia.

    Science.gov (United States)

    Johnston, Amelia J; Hoogenraad, Nicholas J

    2016-07-01

    Although cancer cachexia is a very significant condition that is present in up to 80% of cancer cases, the cause of the condition has remained a puzzle. Cancer cachexia is a condition which is mainly characterised by muscle wasting, mobilization of fat reserves, and overall metabolic disturbance. This review aims to highlight some of the recent findings in cancer cachexia research. It has been recently demonstrated that the expression of a single receptor, fibroblast growth factor-inducible 14, on a tumour can initiate cachexia and that this can be completely ablated by treatment with an antibody against this receptor. Also recently described was the role of parathyroid hormone receptor-binding proteins in causing cachexia through a mechanism where white adipose tissue is replaced with brown adipose tissue. In parallel, work done in drosophila suggests that the impaired insulin signalling is a direct cause of cancer cachexia through the release of an insulin growth factor binding protein that inhibits insulin and insulin-like growth factor 1 signalling. Successful therapies are urgently needed to combat cancer cachexia in the clinic. Recent research is making progress toward discovering the underlying molecular causes of the condition, which could lead to new therapeutic approaches and in the future contribute to more positive clinical outcomes for cancer sufferers.

  4. The pathogenesis and treatment of cardiac atrophy in cancer cachexia.

    Science.gov (United States)

    Murphy, Kate T

    2016-02-15

    Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. In addition to a loss of skeletal muscle mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia is described as cardiac cachexia. The cardiac alterations may be due to underlying heart disease, the cancer itself, or problems initiated by the cancer treatment and, unfortunately, remains largely underappreciated by clinicians and basic scientists. Despite recent major advances in the treatment of cancer, little progress has been made in the treatment of cardiac cachexia in cancer, and much of this is due to lack of information regarding the mechanisms. This review focuses on the cardiac atrophy associated with cancer cachexia, describing some of the known mechanisms and discussing the current and future therapeutic strategies to treat this condition. Above all else, improved awareness of the condition and an increased focus on identification of mechanisms and therapeutic targets will facilitate the eventual development of an effective treatment for cardiac atrophy in cancer cachexia. Copyright © 2016 the American Physiological Society.

  5. Cachexia and pancreatic cancer: Are there treatment options?

    Science.gov (United States)

    Mueller, Tara C; Burmeister, Marc A; Bachmann, Jeannine; Martignoni, Marc E

    2014-01-01

    Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cachexia. However, recent studies have demonstrated that multidimensional therapeutic modalities are able to alleviate pancreatic cancer-associated cachexia and ultimately improve patients’ outcome. In this current review, we propose a stepwise and pragmatic approach to facilitate and standardize the treatment of cachexia in pancreatic cancer patients. This strategy consists of nutritional, dietary, pharmacological, physical and psychological methods. PMID:25071331

  6. Preoperative cancer cachexia and short-term outcomes following surgery.

    Science.gov (United States)

    Mason, Meredith C; Garcia, Jose M; Sansgiry, Shubhada; Walder, Annette; Berger, David H; Anaya, Daniel A

    2016-10-01

    Cancer cachexia is an important measure of physiologic reserve associated with worse survival and represents an actionable factor for the cancer population. However, the incidence of cachexia in surgical cancer patients and its impact on postoperative outcomes are currently unknown. A prospective cohort study enrolling patients having elective cancer surgery (2012-2014) at a Veterans Affairs tertiary referral center. Preoperative cancer cachexia (weight loss ≥5% over 6-mo period before surgery) was the predictor of interest. The primary outcome was 60-d postoperative complications (VA Surgical Quality Improvement Program). Patients were grouped by body mass index (BMI) category (cachexia and BMI was tested for the primary outcome. Multivariate logistic regression was used to examine the association between preoperative cachexia and postoperative complications. Of 253 patients, 16.6% had preoperative cachexia, and 51.8% developed ≥ 1 postoperative complications. Complications were more common in cachectic patients (64.3% versus 49.3%, P = 0.07). This association varied by BMI category, and interaction analysis was significant for those with normal or underweight BMI (BMI cachexia was associated with higher odds of postoperative complications (odds ratios, 5.08 [95% confidence intervals, 1.18-21.88]; P = 0.029). Additional predictors of complications included major surgery (3.19 [1.24-8.21], P = 0.01), ostomy (4.43 [1.68-11.72], P = 0.003), and poor baseline performance status (2.31 [1.05-5.08], P = 0.03). Cancer cachexia is common in surgical patients, and is an important predictor of postoperative complications, though its effect varies by BMI. As a modifiable predictor of worse outcomes, future studies should examine the role of cachexia treatment before cancer surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. [Survey of cachexia in digestive system cancer patients and its impact on clinical outcomes].

    Science.gov (United States)

    Sun, Yandong; Zhang, Bo; Han, Yusong; Jiang, Yi; Zhuang, Qiulin; Gong, Yuda; Wu, Guohao

    2014-10-01

    To investigate cachexia in hospitalized patients with digestive system cancer and evaluate its impact on clinical outcomes. By analyzing the clinical data of 5118 hospitalized patients with digestive system cancer in Zhongshan Hospital of Fudan University from January 2012 to December 2013, cachexia was investigated and clinical outcomes between cachexia patients and non-cachexia patients was compared. The total cachexia rate of hospitalized patients with digestive system cancer was 15.7%(803/5118). The highest rate of cachexia was 34.0%(89/262) in patients with pancreatic cancer followed by gastric cancer 22.4%(261/1164), colon cancer 21.7%(146/672), and rectal cancer 20.1%(117/581). In cachexia group and non-cachexia group, the overall completion rate of radical resection was 67.1%(539/803) and 74.5%(3214/4315) respectively(Pdigestive system cancer. Cachexia has significant adverse effects on clinical outcomes in hospitalized patients with digestive system cancer.

  8. Update on Management of Cancer-Related Cachexia.

    Science.gov (United States)

    Anderson, Lindsey J; Albrecht, Eliette D; Garcia, Jose M

    2017-01-01

    Cachexia is a metabolic syndrome driven by inflammation and characterized by loss of muscle with or without loss of fat mass. In cancer cachexia, the tumor burden and host response induce increased inflammation, decreased anabolic tone, and suppressed appetite leading to the clinical presentation of reduced body weight and quality of life (QOL). There is no approved treatment for cancer cachexia, and commonly used nutritional and anti-inflammatory strategies alone have proven ineffective for management of symptoms. Several other pharmacological agents are currently in development and have shown promise as a clinical strategy in early-phase trials. Recently, it has been proposed that multimodal strategies, with an anabolic focus, initiated early in the disease/treatment progression may provide the most therapeutic potential for symptom management. Here we review the data from recent clinical trials in cancer cachexia including pharmacological, exercise, and nutritional interventions.

  9. The nursing contribution to nutritional care in cancer cachexia.

    Science.gov (United States)

    Hopkinson, Jane B

    2015-11-01

    Cancer cachexia is a complex syndrome. Its defining feature is involuntary weight loss, which arises, in part, because of muscle atrophy and is accompanied by functional decline. International expert consensus recommends that nutritional support and counselling is a component of multimodal therapy for cancer cachexia, as poor nutritional intake can contribute to progression of the syndrome. The present paper focuses on what is presently known about the nursing contribution to nutritional care in cancer cachexia. There is potential for nurses to play an important role. However, obstacles to this include lack of a robust evidence base to support their nutritional care practices and unmet need for education about nutrition in cancer. The nursing role's boundaries and the outcomes of nurse-delivered nutritional care in cancer cachexia are both uncertain and should be investigated.

  10. Emerging markers of cachexia predict survival in cancer patients

    OpenAIRE

    Mondello, Patrizia; Lacquaniti,Antonio; Mondello, Stefania; Bolignano, Davide; Pitini, Vincenzo; Aloisi, Carmela; Buemi, Michele

    2014-01-01

    Background Cachexia may occur in 40% of cancer patients, representing the major cause of death in more than 20% of them. The aim of this study was to investigate the role of leptin, ghrelin and obestatin as diagnostic and predictive markers of cachexia in oncologic patients. Their impact on patient survival was also evaluated. Methods 140 adults with different cancer diagnoses were recruited. Thirty healthy volunteers served as control. Serum ghrelin, obestatin and leptin were tested at basel...

  11. Rikkunshito, a ghrelin potentiator, ameliorates anorexia-cachexia syndrome

    Directory of Open Access Journals (Sweden)

    Naoki eFujitsuka

    2014-12-01

    Full Text Available Anorexia-cachexia syndrome develops during the advanced stages of various chronic diseases in which patients exhibit a decreased food intake, weight loss, and muscle tissue wasting. For these patients, this syndrome is a critical problem leading to an increased rate of morbidity and mortality. The present pharmacological therapies for treating anorexia-cachexia have limited effectiveness. The Japanese herbal medicine rikkunshito is often prescribed for the treatment of anorexia and upper gastrointestinal disorders. Thus, rikkunshito is expected to be beneficial for the treatment of patients with anorexia-cachexia syndrome. In this review, we summarize the effects of rikkunshito and its mechanisms of action on anorexia-cachexia.Persistent loss of appetite leads to a progressive depletion of body energy stores, which is frequently associated with cachexia. Consequently, regulating appetite and energy homeostasis is critically important for treating cachexia. Ghrelin is mainly secreted from the stomach, and it plays an important role in initiating feeding, controlling gastrointestinal motility, and regulating energy expenditure. Recent clinical and basic science studies have demonstrated that the critical mechanism of rikkunshito underlies endogenous ghrelin activity. Interestingly, several components of rikkunshito target multiple gastric and central sites, and regulate the secretion, receptor sensitization, and degradation of ghrelin. Rikkunshito is effective for the treatment of anorexia, body weight loss, muscle wasting, and anxiety-related behavior. Furthermore, treatment with rikkunshito was observed to prolong survival in an animal model of cachexia. The use of a potentiator of ghrelin signaling, such as rikkunshito, may represent a novel approach for the treatment of anorexia-cachexia syndrome.

  12. Cardiac cachexia and muscle wasting: definition, physiopathology, and clinical consequences

    OpenAIRE

    Okoshi, Marina; Romeiro,Fernando; Martinez,Paula; Oliveira,Silvio; Polegato,Bertha; Okoshi,Katashi

    2014-01-01

    Marina P Okoshi,1 Fernando G Romeiro,1 Paula F Martinez,1,2 Silvio A Oliveira Jr,1,2 Bertha F Polegato,1 Katashi Okoshi11Internal Medicine Department, Botucatu Medical School, Sao Paulo State University, UNESP, Sao Paulo, Brazil; 2School of Physiotherapy, Federal University of Mato Grosso do Sul, Campo Grande, BrazilAbstract: Cachexia and muscle wasting are frequently observed in heart failure patients. Cachexia is a predictor of reduced survival, independent of important parameters such as a...

  13. Current pharmacotherapy options for cancer anorexia and cachexia.

    Science.gov (United States)

    Macciò, Antonio; Madeddu, Clelia; Mantovani, Giovanni

    2012-12-01

    Anorexia and cachexia syndrome represents a complex clinical picture that occurs in the late stage of several chronic inflammatory diseases, including cancer. Unless counteracted cancer-related anorexia and cachexia syndrome affects quality of life (QL) and survival. However, to date a standard effective treatment is lacking. The aim of this review is to describe the current pharmacological approaches for anorexia and cachexia syndrome, focusing on cancer-related syndrome. The several pharmacological agents tested so far are discussed, distinguishing them in unproven drugs, effective drugs, and drugs under investigation. Moreover, a section is devoted to the promising use of nutritional supplements and nutraceuticals. The emerging role of a multitargeted combined treatment approach is exhaustively reviewed. Considering the complex clinical picture and the multifactorial pathogenesis of anorexia and cachexia syndrome, we believe that its clinical management requires a multidisciplinary and multipharmacological approach. In our opinion the anorexia and cachexia syndrome treatment should include drugs that target the following conditions: inflammatory status, oxidative stress, nutritional disorders, muscle catabolism, anemia, immunosuppression, and fatigue. The multidimensional therapies for anorexia and cachexia syndrome should ideally be introduced within a context of the "best supportive care," which includes optimal symptom management and careful psychosocial counseling.

  14. Cancer cachexia: global awareness and guideline implementation on the web.

    Science.gov (United States)

    Mauri, Davide; Tsiara, Anna; Valachis, Antonis; Kalopita, Konstantina; Tsali, Lampriani; Tolis, Panagiotis; Polyzos, Nikolaos P

    2013-06-01

    Cancer cachexia is a common associate of cancer and has a negative impact on patients' survival. Nonetheless, cancer cachexia assessment and management are frequently less than satisfactory in daily practice. To scrutinise global cancer cachexia awareness and relative web guideline implementation among oncology societies. Systematical identification of scientific and policymaker oncology societies and their guideline implementation on cancer cachexia. Assessment of the general level of awareness on cancer cachexia and evaluation of intercontinental and national variations on guideline implementation. 144,000 web pages were scrutinised, and 275 oncology societies identified covering a large array of oncology setting (educational/clinical/research/policymaker); 71 were international (African, American, Asian, European, Oceania and Intercontinental), 110 belonged to the top 10 countries with the highest development index and 94 pertained to 10 countries with a long lasting tradition in medical oncology (not included in the top 10 high developed countries). Overall, only 10/275 web sites provided guidelines; six of them (2.2%) provided guidelines for physicians and four (0.7%) for patients. Half of the guidelines (4/10) were outdated. All guidelines for physicians reported references, while only one of the recommendations for patients reported references to support its sentences. Cancer cachexia global awareness appears extremely low; guideline implementation on the web was inconsistent for any category analysed (nation vs continent vs international vs society type vs physician vs patient oriented) and for updating.

  15. Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia.

    Science.gov (United States)

    Fukawa, Tomoya; Yan-Jiang, Benjamin Chua; Min-Wen, Jason Chua; Jun-Hao, Elwin Tan; Huang, Dan; Qian, Chao-Nan; Ong, Pauline; Li, Zhimei; Chen, Shuwen; Mak, Shi Ya; Lim, Wan Jun; Kanayama, Hiro-Omi; Mohan, Rosmin Elsa; Wang, Ruiqi Rachel; Lai, Jiunn Herng; Chua, Clarinda; Ong, Hock Soo; Tan, Ker-Kan; Ho, Ying Swan; Tan, Iain Beehuat; Teh, Bin Tean; Shyh-Chang, Ng

    2016-06-01

    Cachexia is a devastating muscle-wasting syndrome that occurs in patients who have chronic diseases. It is most commonly observed in individuals with advanced cancer, presenting in 80% of these patients, and it is one of the primary causes of morbidity and mortality associated with cancer. Additionally, although many people with cachexia show hypermetabolism, the causative role of metabolism in muscle atrophy has been unclear. To understand the molecular basis of cachexia-associated muscle atrophy, it is necessary to develop accurate models of the condition. By using transcriptomics and cytokine profiling of human muscle stem cell-based models and human cancer-induced cachexia models in mice, we found that cachectic cancer cells secreted many inflammatory factors that rapidly led to high levels of fatty acid metabolism and to the activation of a p38 stress-response signature in skeletal muscles, before manifestation of cachectic muscle atrophy occurred. Metabolomics profiling revealed that factors secreted by cachectic cancer cells rapidly induce excessive fatty acid oxidation in human myotubes, which leads to oxidative stress, p38 activation and impaired muscle growth. Pharmacological blockade of fatty acid oxidation not only rescued human myotubes, but also improved muscle mass and body weight in cancer cachexia models in vivo. Therefore, fatty acid-induced oxidative stress could be targeted to prevent cancer-induced cachexia.

  16. Cachexia in cancer: what is in the definition?

    Science.gov (United States)

    Vanhoutte, Greetje; van de Wiel, Mick; Wouters, Kristin; Sels, Michaël; Bartolomeeussen, Linda; De Keersmaecker, Sven; Verschueren, Caroline; De Vroey, Veronique; De Wilde, Annemieke; Smits, Elke; Cheung, Kin Jip; De Clerck, Liesbeth; Aerts, Petra; Baert, Didier; Vandoninck, Caroline; Kindt, Sofie; Schelfhaut, Sofie; Vankerkhoven, Marc; Troch, Annelies; Ceulemans, Lore; Vandenbergh, Hanne; Leys, Sven; Rondou, Tim; Dewitte, Elke; Maes, Kristel; Pauwels, Patrick; De Winter, Benedicte; Van Gaal, Luc; Ysebaert, Dirk; Peeters, Marc

    2016-01-01

    This study aimed to provide evidence-based results on differences in overall survival (OS) rate to guide the diagnosis of cancer cachexia. Data collection and clinical assessment was performed every 3 months (5 visits): baseline data, muscle strength, nutritional and psychosocial status. 2 definitions on cachexia using different diagnostic criteria were applied for the same patient population. Fearon et al 's definition is based on weight loss, body mass index (BMI) and sarcopenia. Evans et al nuances the contribution of sarcopenia and attaches additional attention to abnormal biochemistry parameters, fatigue and anorexia. The mean OS rates were compared between patients with and without cachexia for both definitions. Based on the population of 167 patients who enrolled, 70% developed cachexia according to Fearon et al 's definition and 40% according to Evans et al 's definition. The OS in the cachectic population is 0.97 and 0.55 years, respectively. The difference in OS between patients with and without cachexia is more significant using the diagnostic criteria of Evans et al . The focus of Fearon et al on weight loss and sarcopenia over-rates the assignment of patients to the cachectic group and OS rates have less prognostic value. This study presents a correlation with prognosis in favour of Evans et al ' definition as a tool for cachexia diagnosis. This means that weight loss and BMI decline are both key factors in patients with cancer leading to cachexia but less decisive as stated by Fearon et al . Instead, extra factors gain importance in order to predict survival, such as chronic inflammation, anaemia, protein depletion, reduced food intake, fatigue, decreased muscle strength and lean tissue depletion. B300201112334.

  17. Cachexia in cancer: what is in the definition?

    Science.gov (United States)

    Vanhoutte, Greetje; van de Wiel, Mick; Wouters, Kristin; Sels, Michaël; Bartolomeeussen, Linda; De Keersmaecker, Sven; Verschueren, Caroline; De Vroey, Veronique; De Wilde, Annemieke; Smits, Elke; Cheung, Kin Jip; De Clerck, Liesbeth; Aerts, Petra; Baert, Didier; Vandoninck, Caroline; Kindt, Sofie; Schelfhaut, Sofie; Vankerkhoven, Marc; Troch, Annelies; Ceulemans, Lore; Vandenbergh, Hanne; Leys, Sven; Rondou, Tim; Dewitte, Elke; Maes, Kristel; Pauwels, Patrick; De Winter, Benedicte; Van Gaal, Luc; Ysebaert, Dirk; Peeters, Marc

    2016-01-01

    Objective This study aimed to provide evidence-based results on differences in overall survival (OS) rate to guide the diagnosis of cancer cachexia. Design Data collection and clinical assessment was performed every 3 months (5 visits): baseline data, muscle strength, nutritional and psychosocial status. 2 definitions on cachexia using different diagnostic criteria were applied for the same patient population. Fearon et al's definition is based on weight loss, body mass index (BMI) and sarcopenia. Evans et al nuances the contribution of sarcopenia and attaches additional attention to abnormal biochemistry parameters, fatigue and anorexia. The mean OS rates were compared between patients with and without cachexia for both definitions. Results Based on the population of 167 patients who enrolled, 70% developed cachexia according to Fearon et al's definition and 40% according to Evans et al's definition. The OS in the cachectic population is 0.97 and 0.55 years, respectively. The difference in OS between patients with and without cachexia is more significant using the diagnostic criteria of Evans et al. The focus of Fearon et al on weight loss and sarcopenia over-rates the assignment of patients to the cachectic group and OS rates have less prognostic value. Conclusion This study presents a correlation with prognosis in favour of Evans et al’ definition as a tool for cachexia diagnosis. This means that weight loss and BMI decline are both key factors in patients with cancer leading to cachexia but less decisive as stated by Fearon et al. Instead, extra factors gain importance in order to predict survival, such as chronic inflammation, anaemia, protein depletion, reduced food intake, fatigue, decreased muscle strength and lean tissue depletion. Trial registration number B300201112334. PMID:27843571

  18. Aliskiren targets multiple systems to alleviate cancer cachexia.

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    Wang, Chaoyi; Guo, Dunwei; Wang, Qiang; You, Song; Qiao, Zhongpeng; Liu, Yong; Dai, Hang; Tang, Hua

    2016-11-01

    To examine the effects of aliskiren, a small-molecule renin inhibitor, on cancer cachexia and to explore the underlying mechanisms. A cancer cachexia model was established by subcutaneously injecting C26 mouse colon carcinoma cells into isogenic BALB/c mice. Aliskiren was administered intragastrically [10 mg/kg body weight (BW)] on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection. Mice that received no C26 injection (healthy controls, HC group) or only C26 injection but not aliskiren (cancer, CA group) were used as controls. BW, tumor growth, whole body functions, and survival were monitored daily in half of the mice in each group, whereas serum, tumors, and gastrocnemius muscles were harvested from the other mice after sacrifice on day 20 for further analysis. Aliskiren significantly alleviated multiple cachexia‑associated symptoms, including BW loss, tumor burden, muscle wasting, muscular dysfunction, and shortened survival. On the molecular level, aliskiren antagonized cachexia‑induced activation of the renin‑angiotensin system (RAS), systematic and muscular inflammation, oxidative stress, and autophagy‑lysosome as well as ubiquitin‑proteasome stimulation. In addition, early administration of aliskiren before cachexia development (AP group) resulted in more robust effects in alleviating cachexia or targeting underlying mechanisms than administration after cachexia development (AT group). Aliskiren exhibited potent anti‑cachexia activities. These activities were achieved through the targeting of at least four mechanisms underlying cachexia development: RAS activation, increase in systematic inflammation, upregulation of oxidative stress, and stimulation of autophagy-lysosome pathway (ALP) and ubiquitin-proteasome pathway (UPP).

  19. Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling.

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    Chen, Xiangzheng; Wu, Yangping; Yang, Tinghan; Wei, Mingtian; Wang, Yuxi; Deng, Xiangbing; Shen, Congcong; Li, Wenting; Zhang, Hang; Xu, Weiyong; Gou, Lantu; Zeng, Yong; Zhang, Yonghui; Wang, Ziqiang; Yang, Jinliang

    2016-05-01

    Cachexia has a devastating impact on survival and quality of life for many cancer patients and contributes to nearly one-third of all cancer deaths; also, it is associated with poor responses to chemotherapy and survival. A better understanding of the underlying mechanisms of cancer-associated cachexia (CAC), coupled with effective therapeutic approaches, will improve management of progressive functional impairment in cancer patients. Salidroside, a phenylpropanoid glycoside in Rhodiola rosea L, has been reported to possess potential anti-fatigue, anti-ageing, and anti-Alzheimer's disease properties. It is widely consumed as a nutritional supplement, but its effects on CAC and the possible mechanism remain a mystery. In the murine models of cachexia induced by CT-26 and Lewis lung carcinoma (LLC) tumour, respectively, main features of CAC were determined after treatment of salidroside or chemotherapy. In vitro experiments were performed using murine C2C12 myotubes, which were treated by tumour necrosis factor-α. Levels of several critical muscle-related signal proteins such as mammalian target of rapamycin (mTOR), p-mTOR, and myosin heavy chain (MyHC) were examined using western blot both in vitro and in vivo. In the present study, we showed the exciting effect of salidroside on the treatment of CAC. In CT-26 and LLC models, respectively, salidroside treatment could effectively preserve the tumour-free body weight, decrease loss of adipose and gastrocnemius muscles, alleviate tumour burden, and prolong their survival time. Additionally, in combined chemotherapy, salidroside could synergistically enhance the anti-tumour activity of cisplatin, especially decreased or eliminated chemotherapy-induced cachexia. Further analysis demonstrated that salidroside could significantly increase expression of mTOR, p-mTOR, and MyHC in gastrocnemius muscle. Also, results in vitro showed that salidroside could not only obviously increase mTOR, p-mTOR, and MyHC expression in C2C12

  20. Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

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    Kliewer, Kara L; Ke, Jia-Yu; Tian, Min; Cole, Rachel M; Andridge, Rebecca R; Belury, Martha A

    2015-01-01

    Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia – before severe fat loss – in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34–42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition. PMID:25457061

  1. Optimal management of cancer anorexia–cachexia syndrome

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    Josep M Argilés

    2010-01-01

    Full Text Available Josep M Argilés, Mireia Olivan, Sílvia Busquets, Francisco Javier López-SorianoDepartament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, SpainAbstract: According to a recent consensus, cachexia is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass. The prominent clinical feature of cachexia is weight loss. Cachexia occurs in the majority of cancer patients before death and it is responsible for the deaths of 22% of cancer patients. Although bodyweight is the most important endpoint of any cachexia treatment, body composition, physical performance and quality of life should be monitored. From the results presented here, one can speculate that a single therapy may not be completely successful in the treatment of cachexia. From this point of view, treatments involving different combinations are more likely to be successful. The objectives of any therapeutic combination are two-fold: an anticatabolic aim directed towards both fat and muscle catabolism and an anabolic objective leading to the synthesis of macromolecules such as contractile proteins.Keywords: wasting, cancer, anorexia, nutraceuticals, drugs

  2. Cancer Cachexia: Cause, Diagnosis, and Treatment.

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    Mattox, Todd W

    2017-10-01

    Patients with cancer frequently experience unintended weight loss due to gastrointestinal (GI) dysfunction caused by the malignancy or treatment of the malignancy. However, others may present with weight loss related to other symptoms not clearly associated with identifiable GI dysfunction such as anorexia and early satiety. Cancer cachexia (CC) is a multifactorial syndrome that is generally characterized by ongoing loss of skeletal muscle mass with or without fat loss, often accompanied by anorexia, weakness, and fatigue. CC is associated with poor tolerance of antitumor treatments, reduced quality of life (QOL), and negative impact on survival. Symptoms associated with CC are thought to be caused in part by tumor-induced changes in host metabolism that result in systemic inflammation and abnormal neurohormonal responses. Unfortunately, there is no single standard treatment for CC. Nutrition consequences of oncologic treatments should be identified early with nutrition screening and assessment. Pharmacologic agents directed at improving appetite and countering metabolic abnormalities that cause inefficient nutrient utilization are currently the foundation for treating CC. Multiple agents have been investigated for their effects on weight, muscle wasting, and QOL. However, few are commercially available for use. Considerations for choosing the most appropriate treatment include effect on appetite, weight, QOL, risk of adverse effects, and cost and availability of the agent.

  3. [Obesity and cardiac cachexia in chronic heart failure].

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    Clauser, M; Altenberger, J

    2013-09-01

    Obesity as well as cardiac cachexia in heart failure patients are not fully understood and therefore of high scientific interest. Obesity as a common risk factor for cardiovascular disease is associated with a high mortality. In contrast obesity in patients suffering from chronic heart failure seems to be accompanied with a favorable outcome in contrast to people with normal weight, known as the obesity paradox. In the last decade there has been growing interest in cachexia, which is common in advanced stages of chronic diseases, such as heart failure, chronic obstructive pulmonary disease (COPD), cancer and renal failure and is associated with a poor prognosis. Until now cachexia has been underdiagnosed and undertreated. This review discusses the complex underlying pathomechanisms as well as potential therapeutic approaches.

  4. The rationale for preventing cancer cachexia: targeting excessive fatty acid oxidation.

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    Qian, Chao-Nan

    2016-07-21

    Cachexia commonly occurs at the terminal stage of cancer and has largely unclear molecular mechanisms. A recent study published in Nature Medicine, entitled "Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia," reveals that cachectic cancer cells can secrete multiple cytokines that induce excessive fatty acid oxidation, which is responsible for muscle loss in cancer cachexia. Inhibition of fatty acid oxidation using etomoxir can increase muscle mass and body weight in cancer cachexia animal models. The usage of stable cachexia animal models is also discussed in this research highlight.

  5. Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia.

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    Shukla, Surendra K; Gebregiworgis, Teklab; Purohit, Vinee; Chaika, Nina V; Gunda, Venugopal; Radhakrishnan, Prakash; Mehla, Kamiya; Pipinos, Iraklis I; Powers, Robert; Yu, Fang; Singh, Pankaj K

    2014-01-01

    Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in view the significant role of metabolic alterations in cancer, we hypothesized that a ketogenic diet may diminish glycolytic flux in tumor cells to alleviate cachexia syndrome and, hence, may provide an efficient therapeutic strategy. We observed reduced glycolytic flux in tumor cells upon treatment with ketone bodies. Ketone bodies also diminished glutamine uptake, overall ATP content, and survival in multiple pancreatic cancer cell lines, while inducing apoptosis. A decrease in levels of c-Myc, a metabolic master regulator, and its recruitment on glycolytic gene promoters, was in part responsible for the metabolic phenotype in tumor cells. Ketone body-induced intracellular metabolomic reprogramming in pancreatic cancer cells also leads to a significantly diminished cachexia in cell line models. Our mouse orthotopic xenograft models further confirmed the effect of a ketogenic diet in diminishing tumor growth and cachexia. Thus, our studies demonstrate that the cachectic phenotype is in part due to metabolic alterations in tumor cells, which can be reverted by a ketogenic diet, causing reduced tumor growth and inhibition of muscle and body weight loss.

  6. Cardiac cachexia and muscle wasting: definition, physiopathology, and clinical consequences

    Directory of Open Access Journals (Sweden)

    Okoshi MP

    2014-11-01

    Full Text Available Marina P Okoshi,1 Fernando G Romeiro,1 Paula F Martinez,1,2 Silvio A Oliveira Jr,1,2 Bertha F Polegato,1 Katashi Okoshi11Internal Medicine Department, Botucatu Medical School, Sao Paulo State University, UNESP, Sao Paulo, Brazil; 2School of Physiotherapy, Federal University of Mato Grosso do Sul, Campo Grande, BrazilAbstract: Cachexia and muscle wasting are frequently observed in heart failure patients. Cachexia is a predictor of reduced survival, independent of important parameters such as age, heart failure functional class, and functional capacity. Muscle and fat wasting can also predict adverse outcome during cardiac failure. Only more recently were these conditions defined in International Consensus. Considering that heart failure is an inflammatory disease, cardiac cachexia has been diagnosed by finding a body weight loss >5%, in the absence of other diseases and independent of other criteria. Muscle wasting has been defined as lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean for healthy individuals between 20 years and 30 years old from the same ethnic group. The etiology of heart failure-associated cachexia and muscle wasting is multifactorial, and the underlying physiopathological mechanisms are not completely understood. The most important factors are reduced food intake, gastrointestinal alterations, immunological activation, neurohormonal abnormalities, and an imbalance between anabolic and catabolic processes. Cachexia and muscle wasting have clinical consequences in several organs and systems including the gastrointestinal and erythropoietic systems, and the heart, previously affected by the primary disease. We hope that a better understanding of the mechanisms involved in their physiopathology will allow the development of pharmacological and nonpharmacological therapies to effectively prevent and treat heart failure-induced cachexia and muscle wasting before significant body

  7. Metabolic signatures imaged in cancer-induced cachexia.

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    Penet, Marie-France; Gadiya, Mayur M; Krishnamachary, Balaji; Nimmagadda, Sridhar; Pomper, Martin G; Artemov, Dmitri; Bhujwalla, Zaver M

    2011-11-15

    Cancer-induced cachexia is a complex and poorly understood life-threatening syndrome that is characterized by progressive weight loss due to metabolic alterations, depletion of lipid stores, and severe loss of skeletal muscle protein. Gaining the ability to noninvasively image the presence or onset of cachexia is important to better treat this condition, to improve the design and optimization of therapeutic strategies, and to detect the responses to such treatments. In this study, we employed noninvasive magnetic resonance spectroscopic imaging (MRSI) and [(18)F]fluoro-2-deoxy-D-glucose ((18)FDG) positron emission tomography (PET) to identify metabolic signatures typical of cachectic tumors, using this information to analyze the types and extents of metabolic changes induced by the onset of cachexia in normal tissues. Cachexia was confirmed by weight loss as well as analyses of muscle tissue and serum. In vivo, cachexia-inducing murine adenocarcinoma (MAC)16 tumors were characterized by higher total choline (tCho) and higher (18)FDG uptake than histologically similar noncachectic MAC13 tumors. A profound depletion of the lipid signal was observed in normal tissue of MAC16 tumor-bearing mice but not within the tumor tissue itself. High-resolution (1)H magnetic resonance spectroscopy (MRS) confirmed the high tCho level observed in cachectic tumors that occurred because of an increase of free choline and phosphocholine. Higher succinate and lower creatine levels were also detected in cachectic tumors. Taken together, these findings enhance our understanding of the effect of cancer on host organs and tissues as well as promote the development of noninvasive biomarkers for the presence of cachexia and identification of new therapeutic targets. ©2011 AACR

  8. Use of routinely available clinical, nutritional, and functional criteria to classify cachexia in advanced cancer patients.

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    Vigano, Antonio A L; Morais, José A; Ciutto, Lorella; Rosenthall, Leonard; di Tomasso, Jonathan; Khan, Sarah; Olders, Henry; Borod, Manuel; Kilgour, Robert D

    2017-10-01

    Cachexia is a highly prevalent syndrome in cancer and chronic diseases. However, due to the heterogeneous features of cancer cachexia, its identification and classification challenge clinical practitioners. To determine the clinical relevance of a cancer cachexia classification system in advanced cancer patients. Beginning with the four-stage classification system proposed for cachexia [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca) and refractory cachexia (RCa)], we assigned patients to these cachexia stages according to five classification criteria available in clinical practice: 1) biochemistry (high C-reactive protein or leukocytes, or hypoalbuminemia, or anemia), 2) food intake (normal/decreased), weight loss: 3) moderate (≤5%) or 4) significant (>5%/past six months) and 5) performance status (Eastern Cooperative Oncology Group Performance Status ≥ 3). We then determined if symptom severity, body composition changes, functional levels, hospitalizations and survival rates varied significantly across cachexia stages. Two-hundred and ninety-seven advanced cancer patients with primary gastrointestinal and lung tumors were included. Patients were classified into Ca (36%), PCa and RCa (21%, respectively) and NCa (15%). Significant (p nutritional and functional outcomes. The lack of statistical difference between PCa and Ca in almost all clinical outcomes examined suggests either that the PCa group includes patients already affected by early cachexia or that more precise criteria are needed to differentiate PCa from Ca patients. More studies are required to validate these findings. Copyright © 2016. Published by Elsevier Ltd.

  9. Mechanisms of metabolic dysfunction in cancer-associated cachexia

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    Petruzzelli, Michele; Wagner, Erwin F.

    2016-01-01

    Metabolic dysfunction contributes to the clinical deterioration observed in advanced cancer patients and is characterized by weight loss, skeletal muscle wasting, and atrophy of the adipose tissue. This systemic syndrome, termed cancer-associated cachexia (CAC), is a major cause of morbidity and mortality. While once attributed solely to decreased food intake, the present description of cancer cachexia is a disorder of multiorgan energy imbalance. Here we review the molecules and pathways responsible for metabolic dysfunction in CAC and the ideas that led to the current understanding. PMID:26944676

  10. Understanding tumor anabolism and patient catabolism in cancer-associated cachexia.

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    Schcolnik-Cabrera, Alejandro; Chávez-Blanco, Alma; Domínguez-Gómez, Guadalupe; Dueñas-González, Alfonso

    2017-01-01

    Cachexia is a multifactorial paraneoplastic syndrome commonly associated with advanced stages of cancer. Cachexia is responsible for poor responses to antitumoral treatment and death in close to one-third of affected patients. There is still an incomplete understanding of the metabolic dysregulation induced by a tumor that leads to the appearance and persistence of cachexia. Furthermore, cachexia is irreversible, and there are currently no guidelines for its diagnosis or treatments for it. In this review, we aim to discuss the current knowledge about cancer-associated cachexia, starting with generalities about cancer as the generator of this syndrome, then analyzing the characteristics of cachexia at the biochemical and metabolic levels in both the tumor and the patient, and finally discussing current therapeutic approaches to treating cancer-associated cachexia.

  11. Understanding tumor anabolism and patient catabolism in cancer-associated cachexia

    Science.gov (United States)

    Schcolnik-Cabrera, Alejandro; Chávez-Blanco, Alma; Domínguez-Gómez, Guadalupe; Dueñas-González, Alfonso

    2017-01-01

    Cachexia is a multifactorial paraneoplastic syndrome commonly associated with advanced stages of cancer. Cachexia is responsible for poor responses to antitumoral treatment and death in close to one-third of affected patients. There is still an incomplete understanding of the metabolic dysregulation induced by a tumor that leads to the appearance and persistence of cachexia. Furthermore, cachexia is irreversible, and there are currently no guidelines for its diagnosis or treatments for it. In this review, we aim to discuss the current knowledge about cancer-associated cachexia, starting with generalities about cancer as the generator of this syndrome, then analyzing the characteristics of cachexia at the biochemical and metabolic levels in both the tumor and the patient, and finally discussing current therapeutic approaches to treating cancer-associated cachexia. PMID:28560061

  12. [Chronic heart failure and cachexia: role of endocrine system].

    Science.gov (United States)

    Dei Cas, A; Muoio, A; Zavaroni, I

    2011-12-01

    Chronic heart failure (CHF) is a major health problem that carries a devastating prognosis. The prognosis worsens considerably once cardiac cachexia has been diagnosed. Neurohormonal, metabolic, hemodynamic and immunological alterations are involved in the initiation and progression of cardiac cachexia. Cachexia is characterized by a hypothalamic inappropriate response to the mechanisms controlling energy homeostasis. Levels of the anorexigenic hormone leptin are decreased whereas the orexigenic gherlin hormone levels are normal or elevated. Nevertheless, energy intake is not increased as expected due to a persistent activation of the proopiomelanocortin (POMC) system (anorexigenic) paralleled by a decreased activity of the neuropeptide Y (NPY, orexigenic) neurons. Cachexia is also characterized by an imbalance in anabolic (impairment in the growth hormone/insulin-like growth factor-I axis, insulin resistance) and catabolic (increased levels of catecholamines, increased cortisol/dehydroepiandrosterone ratio and activation of proinflammatory cytokines such as tumor necrosis factor-alpha, interleuchin-6, interleuchin-1') at the basis of the wasting process. This review discusses the complex role of the endocrine system in modulating energy balance, appetite and metabolism in patients with chronic heart failure. A joint multidisciplinary effort of the cardiologists, immunologists and endocrinologists might be useful to identify the precise mechanisms involved in the neuroendocrine alteration and to develop therapeutic strategies able to improve the prognosis of CHF patients.

  13. The therapeutic potential of exercise to treat cachexia.

    Science.gov (United States)

    Lira, Fábio S; Antunes, Barbara de M M; Seelaender, Marília; Rosa Neto, José C

    2015-12-01

    To discuss the role of physical exercise in the attenuation of cancer cachexia-associated symptoms, and upon the outcome of chemotherapy, with special focus on the anti-inflammatory role of chronic exercise. The review addresses the recent findings regarding the positive effects of endurance and strength exercise training upon metabolic dysfunction, systemic inflammation and body composition alterations in the syndrome of cachexia. The employment of different exercise protocol strategies, in respect to intensity, duration, work load and in concomitance with pharmacological treatment is considered. Cachexia is a multifactorial wasting syndrome afflicting patients with cancer, chronic obstructive pulmonary disease, chronic heart failure, trauma, among other diseases. This condition markedly compromises the quality of life, treatment outcome and survival. Recent literature indicates an unequivocal role of chronic exercise in modulating cachexia and other cancer-associated dysfunctions. Exercise is proposed as a complementary treatment in cancer, and represents a function-preserving, anti-inflammatory and metabolism-modulating strategy with low cost, and high versatility and availability. Furthermore, exercise decreases cancer recurrence and presents a positive impact on public health management, reducing hospitalization and medication costs.

  14. Patient-reported outcomes in cancer cachexia clinical trials.

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    Wheelwright, Sally J; Johnson, Colin D

    2015-12-01

    Patient-reported outcome (PRO) measures should be used when measuring concepts best known to the patient. To maximize the translation of findings into clinical practice, PRO measures that are most relevant for the patient group, should be used and careful reporting of the PRO results is required. The study reviews the use of PRO assessments in cancer cachexia randomized controlled trials. Most, but not all, recent cancer cachexia randomized controlled trials include PRO measures, and significant informative results have been found. PRO measures are rarely the primary endpoint. Most frequently, health -related quality of life and/or symptoms are assessed. However, instruments which are not cancer cachexia-specific are often used. Reporting of PRO data is generally poor. Patient-centred care cannot be delivered without patient-centred outcome information and the assessment of the efficacy of interventions is partly determined by whether there is a measurable perceived patient benefit. To improve the chance of finding significant and useful results, investigators should use cancer cachexia-specific instruments and report their studies carefully.

  15. Spontaneous Physical Activity Downregulates Pax7 in Cancer Cachexia

    Directory of Open Access Journals (Sweden)

    Dario Coletti

    2016-01-01

    Full Text Available Emerging evidence suggests that the muscle microenvironment plays a prominent role in cancer cachexia. We recently showed that NF-kB-induced Pax7 overexpression impairs the myogenic potential of muscle precursors in cachectic mice, suggesting that lowering Pax7 expression may be beneficial in cancer cachexia. We evaluated the muscle regenerative potential after acute injury in C26 colon carcinoma tumor-bearing mice and healthy controls. Our analyses confirmed that the delayed muscle regeneration observed in muscles form tumor-bearing mice was associated with a persistent local inflammation and Pax7 overexpression. Physical activity is known to exert positive effects on cachectic muscles. However, the mechanism by which a moderate voluntary exercise ameliorates muscle wasting is not fully elucidated. To verify if physical activity affects Pax7 expression, we hosted control and C26-bearing mice in wheel-equipped cages and we found that voluntary wheel running downregulated Pax7 expression in muscles from tumor-bearing mice. As expected, downregulation of Pax7 expression was associated with a rescue of muscle mass and fiber size. Our findings shed light on the molecular basis of the beneficial effect exerted by a moderate physical exercise on muscle stem cells in cancer cachexia. Furthermore, we propose voluntary exercise as a physiological tool to counteract the overexpression of Pax7 observed in cancer cachexia.

  16. Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia.

    Science.gov (United States)

    Tsoli, Maria; Swarbrick, Michael M; Robertson, Graham R

    2016-06-01

    Although muscle wasting is the obvious manifestation of cancer cachexia that impacts on patient quality of life, the loss of lipid reserves and metabolic imbalance in adipose tissue also contribute to the devastating impact of cachexia. Depletion of fat depots in cancer patients is more pronounced than loss of muscle and often precedes, or even occurs in the absence of, reduced lean body mass. Rapid mobilisation of triglycerides stored within adipocytes to supply the body with fatty acids in periods of high-energy demand is normally mediated through a well-defined process of lipolysis involving the lipases ATGL, HSL and MGL. Studies into how these lipases contribute to fat loss in cancer cachexia have revealed the prominent role for ATGL in initiating lipolysis during adipose tissue atrophy, together with links between tumour-derived factors and the signalling pathways that control lipid flux within fat cells. The recent findings of increased thermogenesis in brown fat during cancer cachexia indicate that metabolically active adipose tissue contributes to the imbalance in energy homeostasis involved in catabolic wasting. Such energetically futile use of fatty acids liberated from adipose tissue to generate heat represents a maladaptive response in conjunction with anorexia experienced by cancer patients. As IL-6 release by tumours provokes lipolysis and activates the thermogenic programme in brown fat, this review explores the overlap in dysregulated metabolic processes due to inflammatory mediators in cancer cachexia and other disease states characterised by elevated cytokines such as obesity and diabetes. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  17. Cachexia research in Japan: facts and numbers on prevalence, incidence and clinical impact.

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    Konishi, Masaaki; Ishida, Junichi; Springer, Jochen; Anker, Stefan D; von Haehling, Stephan

    2016-12-01

    Even though most clinical data on cachexia have been reported from Western countries, cachexia may be a growing problem in Asia as well, as the population in this area of the world is considerably larger. Considering the current definitions of obesity and sarcopenia in Japan, which are different from the ones in Western countries, the lack of a distinct cachexia definition in Japan is strinking. Only one epidemiological study has reported the prevalence of cachexia using weight loss as part of the definition in patients with stage III or IV non-small cell lung cancer. Although the reported prevalence of 45.6% is within the range of that in Western countries (28-57% in advanced cancer), we cannot compare the prevalence of cachexia in other types of cancer, heart failure, chronic obstructive pulmonary disease (COPD), and kidney disease (CKD) between Japan and Western countries. In patients with heart failure, one third of Japanese patients has a body mass index cachexia in Japan. The rate of underweight patients in COPD has been reported as 31-41% in COPD and seems to be high in comparison to the prevalence of cachexia in Western countries (27-35%). The reported lowest quartile value of BMI (19.6 kg/m2) in CKD may match with the prevalence of cachexia in Western countries (30-60%). The number of clinical trials targeting cachexia is very limited in Japan so far.

  18. Post-translationally modified muscle-specific ubiquitin ligases as circulating biomarkers in experimental cancer cachexia

    Science.gov (United States)

    Mota, Roberto; Rodríguez, Jessica E; Bonetto, Andrea; O’Connell, Thomas M; Asher, Scott A; Parry, Traci L; Lockyer, Pamela; McCudden, Christopher R; Couch, Marion E; Willis, Monte S

    2017-01-01

    Cancer cachexia is a severe wasting syndrome characterized by the progressive loss of lean body mass and systemic inflammation. Up to 80% of cancer patients experience cachexia, with 20-30% of cancer-related deaths directly linked to cachexia. Despite efforts to identify early cachexia and cancer relapse, clinically useful markers are lacking. Recently, we identified the role of muscle-specific ubiquitin ligases Atrogin-1 (MAFbx, FBXO32) and Muscle Ring Finger-1 in the pathogenesis of cardiac atrophy and hypertrophy. We hypothesized that during cachexia, the Atrogin-1 and MuRF1 ubiquitin ligases are released from muscle and migrate to the circulation where they could be detected and serve as a cachexia biomarker. To test this, we induced cachexia in mice using the C26 adenocarcinoma cells or vehicle (control). Body weight, tumor volume, and food consumption were measured from inoculation until ~day 14 to document cachexia. Western blot analysis of serum identified the presence of Atrogin-1 and MuRF1 with unique post-translational modifications consistent with mono- and poly- ubiquitination of Atrogin-1 and MuRF1 found only in cachectic serum. These findings suggest that both increased Atrogin-1 and the presence of unique post-translational modifications may serve as a surrogate marker specific for cachexia. PMID:28979816

  19. Is there a genetic cause for cancer cachexia? – a clinical validation study in 1797 patients

    Science.gov (United States)

    Solheim, T S; Fayers, P M; Fladvad, T; Tan, B; Skorpen, F; Fearon, K; Baracos, V E; Klepstad, P; Strasser, F; Kaasa, S

    2011-01-01

    Background: Cachexia has major impact on cancer patients' morbidity and mortality. Future development of cachexia treatment needs methods for early identification of patients at risk. The aim of the study was to validate nine single-nucleotide polymorphisms (SNPs) previously associated with cachexia, and to explore 182 other candidate SNPs with the potential to be involved in the pathophysiology. Method: A total of 1797 cancer patients, classified as either having severe cachexia, mild cachexia or no cachexia, were genotyped. Results: After allowing for multiple testing, there was no statistically significant association between any of the SNPs analysed and the cachexia groups. However, consistent with prior reports, two SNPs from the acylpeptide hydrolase (APEH) gene showed suggestive statistical significance (P=0.02; OR, 0.78). Conclusion: This study failed to detect any significant association between any of the SNPs analysed and cachexia; although two SNPs from the APEH gene had a trend towards significance. The APEH gene encodes the enzyme APEH, postulated to be important in the endpoint of the ubiquitin system and thus the breakdown of proteins into free amino acids. In cachexia, there is an extensive breakdown of muscle proteins and an increase in the production of acute phase proteins in the liver. PMID:21934689

  20. Rheumatoid cachexia and other nutritional alterations in rheumatologic diseases.

    Science.gov (United States)

    Hurtado-Torres, Gilberto Fabián; González-Baranda, Lourdes Larisa; Abud-Mendoza, Carlos

    2015-01-01

    The prevalence of nutritional alterations in rheumatologic diseases ranges from 4 to 95%, depending on the detection method used. Formerly described as the single term rheumatoid cachexia, nutritional alterations can currently be grouped and subdivided based on the physiopathological mechanisms involved: chronic disease-related inflammatory conditions (cachexia), malnutrition associated to acute malnutrition inflammatory conditions (protein-caloric malnutrition) and starvation-related malnutrition. Clinical manifestations of malnutrition associated to rheumatic diseases vary from the patient with low weight or overweight and obesity; with lean body mass depletion as well as functional repercussions, and impact of quality of life as a common denominator. Additionally, the associated increase in body fat mass increases the risk for cardiovascular morbidity. A multidisciplinary approach towards rheumatic diseases should include aspects oriented towards prevention, early identification, diagnosis and correction of nutritional alterations. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  1. NUTRITIONAL SUPPORT OF SEPTIC PATIENT WITH INITIAL CACHEXIA

    Directory of Open Access Journals (Sweden)

    N.V. Kukhtinova

    2011-01-01

    Full Text Available Enteral nutrition provided to children in critical state is necessary area of pediatrician’s activity in children’s hospital. Enteral nutrition is able to improve the prognosis of the disease significantly along with maintenance of essential functions and treatment of pathologic process, decrease of duration of stay in intensive care department. Proper choice of method and volume of nutritional support and product for medical treatment depending on clinical situation is significant problem. The clinical case described in the article illustrates efficacy of modern technologies in correction of protein and energy deficiency in patient with severe sepsis and multiple organ failure developed as a result of severe untreated cystic fibrosis with cachexia and uncontrolled chronic pseudomonas infection as complications.Key words: children, enteral nutrition, cystic fibrosis, sepsis, cachexia.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 208–210

  2. A role of active brown adipose tissue in cancer cachexia?

    Directory of Open Access Journals (Sweden)

    Emiel Beijer

    2012-06-01

    Full Text Available Until a few years ago, adult humans were not thought to have brown adipose tissue (BAT. Now, this is a rapidly evolving field of research with perspectives in metabolic syndromes such as obesity and new therapies targeting its bio-energetic pathways. White, brown and socalled brite adipose fat seem to be able to trans-differentiate into each other, emphasizing the dynamic nature of fat tissue for metabolism. Human and animal data in cancer cachexia to date provide some evidence for BAT activation, but its quantitative impact on energy expenditure and weight loss is controversial. Prospective clinical studies can address the potential role of BAT in cancer cachexia using 18F-fluorodeoxyglucose positron emission tomography-computed tomography scanning, with careful consideration of co-factors such as diet, exposure to the cold, physical activity and body mass index, that all seem to act on BAT recruitment and activity.

  3. Emerging markers of cachexia predict survival in cancer patients.

    Science.gov (United States)

    Mondello, Patrizia; Lacquaniti, Antonio; Mondello, Stefania; Bolignano, Davide; Pitini, Vincenzo; Aloisi, Carmela; Buemi, Michele

    2014-11-16

    Cachexia may occur in 40% of cancer patients, representing the major cause of death in more than 20% of them. The aim of this study was to investigate the role of leptin, ghrelin and obestatin as diagnostic and predictive markers of cachexia in oncologic patients. Their impact on patient survival was also evaluated. 140 adults with different cancer diagnoses were recruited. Thirty healthy volunteers served as control. Serum ghrelin, obestatin and leptin were tested at baseline and after a follow-up period of 18 months. Ghrelin levels were significantly higher in cancer patients than in healthy subjects (573.31 ± 130 vs 320.20 ± 66.48 ng/ml, p obestatin (17.42 ± 7.12 vs 24.89 ± 5.54 ng/ml, p obestatin (AUC 0.798; sensitivity 74.5%; specificity 81.5%) and leptin (AUC 0.828; sensitivity 79%; specificity 73%) was superior to that of albumin (AUC 0.547; sensitivity 63%, specificity 69.4%) for detecting cachexia among cancer patients. On Cox multivariate analyses ghrelin (HR 1.02; 95% CI 1.01 - 1.03; p cancer patients.

  4. The influence of different muscle mass measurements on the diagnosis of cancer cachexia.

    Science.gov (United States)

    Blauwhoff-Buskermolen, Susanne; Langius, Jacqueline A E; Becker, Annemarie; Verheul, Henk M W; de van der Schueren, Marian A E

    2017-08-01

    Progressive loss of muscle mass is a major characteristic of cancer cachexia. Consensus definitions for cachexia provide different options to measure muscle mass. This study describes the effect of different methods to determine muscle mass on the diagnosis of cancer cachexia. In addition, the association of cachexia with other features of cachexia, quality of life, and survival was explored. Prior to chemotherapy, cachexia was assessed by weight loss, body mass index, and muscle mass measurements, the latter by mid-upper arm muscle area (MUAMA), computed tomography (CT) scans, and bio-electrical impedance analysis (BIA). In addition, appetite, inflammation, muscle strength, fatigue, quality of life, and survival were measured, and associations with cachexia were explored. Included were 241 patients with advanced cancer of the lung (36%), colon/rectum (31%), prostate (18%), or breast (15%). Mean age was 64 ± 10 years; 54% was male. Prevalence of low muscle mass was as follows: 13% with MUAMA, 59% with CT, and 93% with BIA. In turn, the prevalence of cachexia was 37, 43, and 48%, whereby weight loss >5% was the most prominent component of being defined cachectic. Irrespective of type of muscle measurement, patients with cachexia presented more often with anorexia, inflammation, low muscle strength, and fatigue and had lower quality of life. Patients with cachexia had worse overall survival compared with patients without cachexia: HRs 2.00 (1.42-2.83) with MUAMA, 1.64 (1.15-2.34) with CT, and 1.50 (1.05-2.14) with BIA. Although the prevalence of low muscle mass in patients with cancer depended largely on the type of muscle measurement, this had little influence on the diagnosis of cancer cachexia (as the majority of patients was already defined cachectic based on weight loss). New studies are warranted to further elucidate the additional role of muscle measurements in the diagnosis of cachexia and the association with clinical outcomes. © 2017 The Authors

  5. Megestrol acetate for treatment of anorexia-cachexia syndrome.

    Science.gov (United States)

    Ruiz Garcia, Vicente; López-Briz, Eduardo; Carbonell Sanchis, Rafael; Gonzalvez Perales, Jose Luis; Bort-Marti, Sylvia

    2013-03-28

    This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation. To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies. We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012. Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology. Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables. We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo

  6. Michelangelo, the Sistine Chapel and the “secret” of cancer cachexia

    African Journals Online (AJOL)

    Diseaseassociated malnutrition is defined as the anorexia-cachexia syndrome, to differentiate this clinical condition from malnutrition resulting from simple starvation, which responds to nutritional support. The pathogenesis of the anorexia-cachexia syndrome is multifactorial, but moderate yet persistent inflammation plays a ...

  7. [Assessment of Cachexia in Head and Neck Cancer Patients Based on a Modified Glasgow Prognostic Score].

    Science.gov (United States)

    Matsuzuka, Takashi; Suzuki, Masahiro; Saijoh, Satoshi; Ikeda, Masakazu; Imaizumi, Mitsumasa; Nomoto, Yukio; Matsui, Takamichi; Tada, Yasuhiro; Omori, Koichi

    2016-02-01

    We retrospectively analyzed 54 patients who died of head and neck squamous cell caricinoma regarding the process and duration of cachexia using the modified Glasgow Prognostic Score (mGPS). The patients were classified as having cachexia when the serum albumin level was less than 3.5 mg/dL and the C-reactive protein (CRP) level was more than 0.5 mg/dL. The number of patients with cachexia was eight (8%) at the first visit and 50 (93%) at the time of death. In the 50 patients, the median and average time of having cachexia was 59 and 95 days, respectively. Thirty-two of the 50 patients (64%) died within three months after the presence of cachexia was confirmed. In this study, the time of having cachexia was so short, then the policy of care should be converted from aggressive into supportive in patients classified as having cachexia. mGPS would be an accurate assessment tool for cachexia and ascertain the end stage of head and neck cancer patients.

  8. Molecular Pathways: Cachexia Signaling-A Targeted Approach to Cancer Treatment.

    Science.gov (United States)

    Miyamoto, Yuji; Hanna, Diana L; Zhang, Wu; Baba, Hideo; Lenz, Heinz-Josef

    2016-08-15

    Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively affects quality of life and portends a poor prognosis. Numerous molecular substrates and mechanisms underlie the dysregulation of skeletal muscle synthesis and degradation observed in cancer cachexia, including proinflammatory cytokines (TNFα, IL1, and IL6), and the NF-κB, IGF1/AKT/mTOR, and myostatin/activin-SMAD pathways. Recent preclinical and clinical studies have demonstrated that anti-cachexia drugs (such as MABp1 and soluble receptor antagonist of myostatin/activin) not only prevent muscle wasting but also may prolong overall survival. In this review, we focus on the significance of cachexia signaling in patients with cancer and highlight promising drugs targeting tumor cachexia in clinical development. Clin Cancer Res; 22(16); 3999-4004. ©2016 AACR. ©2016 American Association for Cancer Research.

  9. Drugs in development for treatment of patients with cancer-related anorexia and cachexia syndrome

    Directory of Open Access Journals (Sweden)

    Mantovani G

    2013-08-01

    Full Text Available Giovanni Mantovani, Clelia Madeddu, Antonio Macciò Department of Medical Oncology, University of Cagliari, Cagliari, Italy Abstract: Cancer-related anorexia and cachexia syndrome (CACS is a complex multifactorial condition, with loss of lean body mass, chronic inflammation, severe metabolic derangements, reduced food intake, reduced physical activity, and poor quality of life as key symptoms. Cachexia recognizes different phases or stages, moving from precachexia through overt cachexia to advanced or refractory cachexia. The purpose of this review is to describe currently effective approaches for the treatment of cachexia, moving forward to drugs and treatments already shown to be effective but needing further clinical trials to confirm their efficacy. We then introduce novel promising investigational drugs and approaches which, based on a strong rationale from the most recent data on the molecular targets/pathways driving the pathophysiology of cachexia, need to be tested either in currently ongoing or appropriate future clinical trials to confirm their clinical potential. Although different drugs and treatments have been tested, we can speculate that a single therapy may not be completely successful. Indeed, considering the complex clinical picture and the multifactorial pathogenesis of CACS, we believe that its clinical management requires a multidisciplinary and multitargeted approach. In our opinion, appropriate treatment for cachexia should target the following conditions: inflammatory status, oxidative stress, nutritional disorders, muscle catabolism, immunosuppression, quality of life, and above all, fatigue. A comprehensive list of the most interesting and effective multitargeted treatments is reported and discussed, with the aim of suggesting the most promising with regard to clinical outcome. A critical issue is that of testing therapies at the earliest stages of cachexia, possibly at the precachexia stage, with the aim of preventing

  10. Sex Differences in the Relationship of IL-6 Signaling to Cancer Cachexia Progression

    Science.gov (United States)

    Hetzler, Kimbell L.; Hardee, Justin P.; Puppa, Melissa J.; Narsale, Aditi A.; Sato, Shuichi; Davis, J. Mark; Carson, James A.

    2015-01-01

    A devastating aspect of cancer cachexia is severe loss of muscle and fat mass. Though cachexia occurs in both sexes, it is not well-defined in the female. The Apc Min/+ mouse is genetically predisposed to develop intestinal tumors; circulating IL-6 is a critical regulator of cancer cachexia in the male Apc Min/+ mouse. The purpose of this study was to examine the relationship between IL-6 signaling and cachexia progression in the female Apc Min/+ mouse. Male and female Apc Min/+ mice were examined during the initiation and progression of cachexia. Another group of females had IL-6 overexpressed between 12-14 weeks or 15-18 weeks of age to determine whether IL-6 could induce cachexia. Cachectic female Apc Min/+ mice lost body weight, muscle mass, and fat mass; increased muscle IL-6 mRNA expression was associated with these changes, but circulating IL-6 levels were not. Circulating IL-6 levels did not correlate with downstream signaling in muscle in the female. Muscle IL-6r mRNA expression and SOCS3 mRNA expression as well as muscle IL-6r protein and STAT3 phosphorylation increased with severe cachexia in both sexes. Muscle SOCS3 protein increased in cachectic females but decreased in cachectic males. IL-6 overexpression did not affect cachexia progression in female Apc Min/+ mice. Our results indicate that female Apc Min/+ mice undergo cachexia progression that is at least initially IL-6-independent. Future studies in the female will need to determine mechanisms underlying regulation of IL-6 response and cachexia induction. PMID:25555992

  11. The role of adipose tissue in cancer-associated cachexia.

    Science.gov (United States)

    Vaitkus, Janina A; Celi, Francesco S

    2017-03-01

    Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing

  12. Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, B.M. [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States); Frye, G.S.; Ahn, B.; Ferreira, L.F. [1864 Stadium Road, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32610 (United States); Judge, A.R., E-mail: arjudge@phhp.ufl.edu [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States)

    2013-06-07

    Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

  13. Cancer as a Proinflammatory Environment: Metastasis and Cachexia

    Science.gov (United States)

    Inácio Pinto, Nelson; Carnier, June; Oyama, Lila M.; Otoch, Jose Pinhata; Alcântara, Paulo Sergio; Tokeshi, Flavio; Nascimento, Claudia M.

    2015-01-01

    The development of the syndrome of cancer cachexia and that of metastasis are related with a poor prognostic for cancer patients. They are considered multifactorial processes associated with a proinflammatory environment, to which tumour microenvironment and other tissues from the tumour bearing individuals contribute. The aim of the present review is to address the role of ghrelin, myostatin, leptin, HIF, IL-6, TNF-α, and ANGPTL-4 in the regulation of energy balance, tumour development, and tumoural cell invasion. Hypoxia induced factor plays a prominent role in tumour macro- and microenvironment, by modulating the release of proinflammatory cytokines. PMID:26508818

  14. A systematic review of health-related quality of life instruments in patients with cancer cachexia.

    Science.gov (United States)

    Wheelwright, Sally; Darlington, Anne-Sophie; Hopkinson, Jane B; Fitzsimmons, Deborah; White, Alice; Johnson, Colin D

    2013-09-01

    Assessing the health-related quality of life (HRQOL) of cancer patients with cachexia is particularly important because treatments for cachexia are currently aimed at palliation and treatment efficacy must be measured in ways other than survival. The aim of this systematic review was to evaluate HRQOL assessment in cancer patients with cachexia. Using guidance from the Centre for Reviews and Dissemination, relevant databases were searched from January 1980 to January 2012 with terms relating to cancer, cachexia and HRQOL for papers including adult cancer patients with cachexia or documented weight loss at baseline. We found one cachexia-specific instrument, the Functional Assessment of Anorexia/Cachexia Therapy, but the tool has not been fully validated, does not cover all the relevant domains and the consensus-based standards for the selection of health status measurement instruments checklist highlighted a number of weaknesses in the methodological quality of the validation study. Sixty-seven studies assessed HRQOL in cachectic or weight-losing cancer patients. Most used generic cancer HRQOL instruments, limiting the amount of useful information they provide. A modified version of the Efficace minimum data checklist demonstrated that the quality of reporting on HRQOL tool use was inadequate in many of the studies. A negative relationship between HRQOL and weight loss was found in 23 of the 27 studies which directly examined this. There is a pressing need for a well-designed HRQOL tool for use with this patient group in both clinical trials and clinical practice.

  15. Understanding cancer-induced cachexia: imaging the flame and its fuel.

    Science.gov (United States)

    Penet, Marie-France; Winnard, Paul T; Jacobs, Michael A; Bhujwalla, Zaver M

    2011-12-01

    One of the most under explored and yet devastating consequences of cancer is cachexia, a condition in which the body is consumed by deranged carbohydrate, lipid and protein metabolism that is induced by inflammatory cytokines. Cachexia is associated with poor treatment outcome, fatigue and poor quality of life. Because of its multifactorial characteristics, it has been difficult to understand the impact of the tumor on body organs and the sequence of events that leads to cachexia. Such insights are critically important in identifying therapeutic strategies. The ability to understand the interaction between the tumor and normal tissues and to noninvasively image the development of this condition would be invaluable in identifying critical stages when cachexia becomes life-threatening. Current multimodality molecular and functional imaging capabilities provide unique opportunities to study cachexia holistically in preclinical models and clinically. In this review we have provided examples of how state-of-the-art imaging techniques in combination with molecular characterization can be used to understand cancer-induced cachexia. Such studies will lead to clinically translatable indices for the early detection of this condition and will identify novel targets to inhibit the cachexia cascade.

  16. Sarcopenia, cachexia, and muscle performance in heart failure: Review update 2016.

    Science.gov (United States)

    Saitoh, Masakazu; Ishida, Junichi; Doehner, Wolfram; von Haehling, Stephan; Anker, Markus S; Coats, Andrew J S; Anker, Stefan D; Springer, Jochen

    2017-07-01

    Cachexia in the context of heart failure (HF) has been termed cardiac cachexia, and represents a progressive involuntary weight loss. Cachexia is mainly the result of an imbalance in the homeostasis of muscle protein synthesis and degradation due to a lower activity of protein synthesis pathways and an over-activation of protein degradation. In addition, muscle wasting leads to of impaired functional capacity, even after adjusting for clinical relevant variables in patients with HF. However, there is no sufficient therapeutic strategy in muscle wasting in HF patients and very few studies in animal models. Exercise training represents a promising intervention that can prevent or even reverse the process of muscle wasting, and worsening the muscle function and performance in HF with muscle wasting and cachexia. The pathological mechanisms and effective therapeutic approach of cardiac cachexia remain uncertain, because of the difficulty to establish animal cardiac cachexia models, thus novel animal models are warranted. Furthermore, the use of improved animal models will lead to a better understanding of the pathways that modulate muscle wasting and therapeutics of muscle wasting of cardiac cachexia. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Ovarian function's role during cancer cachexia progression in the female mouse.

    Science.gov (United States)

    Hetzler, Kimbell L; Hardee, Justin P; LaVoie, Holly A; Murphy, E Angela; Carson, James A

    2017-05-01

    Cachexia is a debilitating condition that occurs with chronic disease, including cancer; our research has shown that some regulation of cancer cachexia progression is affected by sex differences. The ApcMin/+ mouse is genetically predisposed to develop intestinal tumors; IL-6 signaling and hypogonadism are associated with cachexia severity in the male. This relationship in the female warrants further investigation, as we have shown that the ability of IL-6 to induce cachexia differs between the sexes. Since ovarian reproductive function relies on a complex system of endocrine signaling to affect whole body homeostasis, we examined the relationship between ovarian reproductive function and progression of cancer cachexia in the female ApcMin/+ mouse. Our study of ovarian reproductive function in female ApcMin/+ mice showed disease-related cessation of estrous cycling (acyclicity) in 38% of mice. Acyclicity, including morphological and functional losses and enhanced muscle inflammatory gene expression, was associated with severe cachexia. Interestingly, ovariectomy rescued body weight and muscle mass and function but increased muscle sensitivity to systemic IL-6 overexpression. In conclusion, our results provide evidence for a relationship between ovarian reproductive function and cachexia progression in female ApcMin/+ mice. Copyright © 2017 the American Physiological Society.

  18. An analysis of the relationship between metastases and cachexia in lung cancer patients.

    Science.gov (United States)

    Shiono, Masatoshi; Huang, Kan; Downey, Robert J; Consul, Nikita; Villanueva, Nicolas; Beck, Kristen; Fenn, Kathleen; Dietz, Donald; Yamaguchi, Takuhiro; Kato, Shunsuke; Divgi, Chaitanya; Kalinsky, Kevin; Wei, Ying; Zhang, Yuan; Borczuk, Alain C; Inoue, Akira; Halmos, Balazs; Acharyya, Swarnali

    2016-09-01

    Weight loss and hematogenous metastases are poor prognosis factors in lung cancer patients that can but do not necessarily co-occur. We retrospectively investigated the clinical association between cachexia, tumor characteristics (such as metastatic burden and mutational status), and treatment in lung cancer patients. The medical records of 394 lung cancer patients from two institutions (Columbia University, USA and Tohoku University, Japan) were reviewed. Information collected included the presence of cachexia, histologic subtype, tumor stage, number of metastases, mutation status, treatment, and survival. Descriptive statistics were performed. Only stage IV patients exhibited >5% weight loss (0.8%, 2.2%, 3.6%, and 5.1%, for stages I to IV; P = 0.0001). Patients with metastases developed cachexia more often than patients without metastases independent of treatment (6.0% and 7.1% weight loss in patients with metastases vs. 2.5% and 2.0% in patients without metastases, before [P = 0.0001] and after [P cachexia had worse survival than patients without cachexia (hazard ratio, 2.94; 95% confidence interval, 2.08-4.16; P cachexia might be linked intrinsically and are independent of treatments administered. KRAS-mutated tumors were more commonly associated with cachexia. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  19. Possible Involvement of Insulin Resistance in the Progression of Cancer Cachexia in Mice.

    Science.gov (United States)

    Ohsawa, Masahiro; Murakami, Tomoyasu; Kume, Kazuhiko

    2016-01-01

    Malnutrition is a common problem among cancer patients, affecting up to 85% of patients with certain cancers. In severe cases, malnutrition can progress to cachexia, a specific form of malnutrition characterized by loss of lean body mass and muscle wasting. Although this muscle wasting might be a product of enhanced protein degradation, the precise mechanisms of cancer cachexia are not fully elucidated. Based on basic and clinical research, glucose intolerance and insulin resistance have been postulated to be associated with cancer cachexia. Since insulin in the skeletal muscle inhibits protein degradation and promotes protein synthesis, insulin resistance could be a possible cause of cancer cachexia. Therefore, we investigated the involvement of insulin resistance in the development of cancer cachexia in tumor-bearing mice. The signaling protein in the insulin cascade was attenuated in the skeletal muscle and hypothalamus from tumor-bearing mice. We identified Chrysanthemum morifolium RAMAT., known as Kikuka, as a peroxisome proliferator-activated receptor γ (PPARγ) ligand. Treatment with Kikuka attenuates the skeletal muscle changes in tumor-bearing mice. These results suggest that this natural PPARγ activator might be an attractive candidate for the treatment of cancer cachexia. In the symposium, we presented the PPARγ activator-induced improvement of cancer cachexia.

  20. MAP3K11/GDF15 axis is a critical driver of cancer cachexia

    Science.gov (United States)

    Tao, Julie; Liu, Qing; Nicoletti, Richard; Feng, Bin; Krieger, Brian; Mazsa, Elizabeth; Siddiquee, Zakir; Wang, Ruoji; Huang, Lucia; Shen, Luhua; Lin, Jie; Vigano, Antonio; Chiu, M. Isabel; Weng, Zhigang; Winston, William; Weiler, Solly

    2015-01-01

    Abstract Background Cancer associated cachexia affects the majority of cancer patients during the course of the disease and thought to be directly responsible for about a quarter of all cancer deaths. Current evidence suggests that a pro‐inflammatory state may be associated with this syndrome although the molecular mechanisms responsible for the development of cachexia are poorly understood. The purpose of this work was the identification of key drivers of cancer cachexia that could provide a potential point of intervention for the treatment and/or prevention of this syndrome. Methods Genetically engineered and xenograft tumour models were used to dissect the molecular mechanisms driving cancer cachexia. Cytokine profiling from the plasma of cachectic and non‐cachectic cancer patients and mouse models was utilized to correlate circulating cytokine levels with the cachexia phenotype. Results Utilizing engineered tumour models we identified MAP3K11/GDF15 pathway activation as a potent inducer of cancer cachexia. Increased expression and high circulating levels of GDF15 acted as a key mediator of this process. In animal models, tumour‐produced GDF15 was sufficient to trigger the cachexia phenotype. Elevated GDF15 circulating levels correlated with the onset and progression of cachexia in animal models and in patients with cancer. Inhibition of GDF15 biological activity with a specific antibody reversed body weight loss and restored muscle and fat tissue mass in several cachectic animal models regardless of their complex secreted cytokine profile. Conclusions The combination of correlative observations, gain of function, and loss of function experiments validated GDF15 as a key driver of cancer cachexia and as a potential therapeutic target for the treatment and/or prevention of this syndrome. PMID:27239403

  1. Early suppression of adipocyte lipid turnover induces immunometabolic modulation in cancer cachexia syndrome.

    Science.gov (United States)

    Henriques, Felipe Santos; Sertié, Rogério Antônio Laurato; Franco, Felipe Oliveira; Knobl, Pamela; Neves, Rodrigo Xavier; Andreotti, Sandra; Lima, Fabio Bessa; Guilherme, Adilson; Seelaender, Marilia; Batista, Miguel Luiz

    2017-05-01

    Cancer cachexia is a multifactorial syndrome characterized by body weight loss, atrophy of adipose tissue (AT) and systemic inflammation. However, there is limited information regarding the mechanisms of immunometabolic response in AT from cancer cachexia. Male Wistar rats were inoculated with 2 × 107 of Walker 256 tumor cells [tumor bearing (TB) rats]. The mesenteric AT (MeAT) was collected on d 0, 4, 7 (early stage), and 14 (cachexia stage) after tumor cell injection. Surgical biopsies for MeAT were obtained from patients who had gastrointestinal cancer with cachexia. Lipolysis showed an early decrease in glycerol release in TB d 4 (TB4) rats in relation to the control, followed by a 6-fold increase in TB14 rats, whereas de novo lipogenesis was markedly lower in the incorporation of glucose into fatty acids in TB14 rats during the development of cachexia. CD11b and CD68 were positive in TB7 and TB14 rats, respectively. In addition, we found cachexia stage results similar to those of animals in MeAT from patients: an increased presence of CD68+, iNOS2+, TNFα+, and HSL+ cells. In summary, translational analysis of MeAT from patients and an animal model of cancer cachexia enabled us to identify early disruption in Adl turnover and subsequent inflammatory response during the development of cancer cachexia.-Henriques, F. S., Sertié, R. A. L., Franco, F. O., Knobl, P., Neves, R. X., Andreotti, S., Lima, F. B., Guilherme, A., Seelaender, M., Batista, M. L., Jr. Early suppression of adipocyte lipid turnover induces immunometabolic modulation in cancer cachexia syndrome. © FASEB.

  2. Comprehensive proteome analysis of human skeletal muscle in cachexia and sarcopenia: a pilot study.

    Science.gov (United States)

    Ebhardt, H Alexander; Degen, Simone; Tadini, Valentina; Schilb, Alain; Johns, Neil; Greig, Carolyn A; Fearon, Kenneth C H; Aebersold, Ruedi; Jacobi, Carsten

    2017-08-01

    Cancer cachexia (cancer-induced muscle wasting) is found in a subgroup of cancer patients leaving the patients with a poor prognosis for survival due to a lower tolerance of the chemotherapeutic drug. The cause of the muscle wasting in these patients is not fully understood, and no predictive biomarker exists to identify these patients early on. Skeletal muscle loss is an inevitable consequence of advancing age. As cancer frequently occurs in old age, identifying and differentiating the molecular mechanisms mediating muscle wasting in cancer cachexia vs. age-related sarcopenia are a challenge. However, the ability to distinguish between them is critical for early intervention, and simple measures of body weight may not be sufficiently sensitive to detect cachexia early. We used a range of omics approaches: (i) undepleted proteome was quantified using advanced high mass accuracy mass spectrometers in SWATH-MS acquisition mode; (ii) phospho epitopes were quantified using protein arrays; and (iii) morphology was assessed using fluorescent microscopy. We quantified the soluble proteome of muscle biopsies from cancer cachexia patients and compared them with cohorts of cancer patients and healthy individuals with and without age-related muscle loss (aka age-related sarcopenia). Comparing the proteomes of these cohorts, we quantified changes in muscle contractile myosins and energy metabolism allowing for a clear identification of cachexia patients. In an in vitro time lapse experiment, we mimicked cancer cachexia and identified signal transduction pathways governing cell fusion to play a pivotal role in preventing muscle regeneration. The work presented here lays the foundation for further understanding of muscle wasting diseases and holds the promise of overcoming ambiguous weight loss as a measure for defining cachexia to be replaced by a precise protein signature. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on

  3. [Role of Activin A and Myostatin in cancer cachexia].

    Science.gov (United States)

    Thissen, Jean-Paul; Loumaye, Audrey

    2013-05-01

    Recent works suggest that Activin A (ActA) and Myostatin (Mstn), two members of the TGFβ superfamily, could contribute to skeletal muscle atrophy observed in some cancers. It is known that several human tumoral cell lines synthesize and secrete ActA and Mstn. In addition, systemic treatment with ActA and Mstn in mice induce muscle atrophy. Likewise, Inhibin-α knock-out mice, which are characterized by elevated circulating levels of ActA, exhibit muscle atrophy and die of cachexia. Finally, administration of ActA and Mstn antagonists prevents muscular atrophy and mortality induced by some animal tumors. Collectively, these findings suggest that ActA or Mstn production by several cancers could contribute to cachexia and thus to mortality associated with some cancers in human. This hypothesis is very interesting since new molecules that are able to inhibit ActA and Mstn, in particularly the sActRIIB, are under development. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Microbiological, Physicochemical, and Histological Analyses of Broiler Carcasses with Cachexia

    Directory of Open Access Journals (Sweden)

    LC Nery

    Full Text Available ABSTRACT Broiler carcasses presenting cachexia, as determined by the federal inspection agency, were submitted to microbiological, physicochemical, and histological analyses. Over a 2-month period, 278 carcasses from straight-run flocks of 43- to 48-d-old Cobb broilers from two different farms were condemned due to cachexia and subjected to gross examination in the final inspection sector. Out of the 278 carcasses, 131 did not present any gross signs of infection, and were submitted to microbiological analyses (n=83, physicochemical analyses (n=28, and viscera and muscle samples of 20 carcasses were evaluated by histology. The microbiological results of cachectic carcasses complied with the current legislation on the consumption of fresh poultry meat. Lower lipid and higher protein, moisture, and volatile matter contents, and higher pH (p<0.05 were determined in the cachectic than in the control carcasses from a same flock, but no ash content differences. All carcasses were negative for hydrogen sulfide. The histological analysis showed that65% of the cachectic carcasses did not have any muscle injury, 20% showed mild hyalinization and 15% moderate proliferation of fibrous connective tissue. The findings of this study indicate the importance of further technical and scientific studies on the utilization of cachectic broiler carcasses for the manufacture of edible products, rather than whole carcasses rendering, thereby preventing the resulting economic losses.

  5. Cachexia in chronic obstructive pulmonary disease: new insights and therapeutic perspective

    Science.gov (United States)

    Sanders, Karin J. C.; Kneppers, Anita E. M.; van de Bool, Coby; Langen, Ramon C. J.

    2015-01-01

    Abstract Cachexia and muscle wasting are well recognized as common and partly reversible features of chronic obstructive pulmonary disease (COPD), adversely affecting disease progression and prognosis. This argues for integration of weight and muscle maintenance in patient care. In this review, recent insights are presented in the diagnosis of muscle wasting in COPD, the pathophysiology of muscle wasting, and putative mechanisms involved in a disturbed energy balance as cachexia driver. We discuss the therapeutic implications of these new insights for optimizing and personalizing management of COPD‐induced cachexia. PMID:27066314

  6. Validation of the Chinese version of functional assessment of anorexia-cachexia therapy (FAACT) scale for measuring quality of life in cancer patients with cachexia.

    Science.gov (United States)

    Zhou, Ting; Yang, Kaixiang; Thapa, Sudip; Fu, Qiang; Jiang, Yongsheng; Yu, Shiying

    2017-04-01

    The assessment of quality of life (QOL) is an important part of cachexia management for cancer patients. Functional assessment of anorexia-cachexia therapy (FAACT), a specific QOL instrument for cachexia patients, has not been validated in Chinese population. The aim of this study was to validate the FAACT scale in Chinese cancer patients for its future use. Eligible cancer patients were included in our study. Patients' demographic and clinical characteristics were collected from the electronic medical records. Patients were asked to complete the Chinese version of FAACT scale and the MD Anderson symptom inventory (MDASI), and then the reliability and validity were analyzed. A total of 285 patients were enrolled in our study, data of 241 patients were evaluated. Coefficients of Cronbach's alpha, test-retest and split-half analyses were all greater than 0.8, which indicated an excellent reliability for FAACT scale. In item-subscale correlation analysis and factor analysis, good construct validity for FAACT scale was found. The correlation between FAACT and MDASI interference subscale showed reasonable criterion-related validity, and for further clinical validation, the FAACT scale showed excellent discriminative validity for distinguishing patients in different cachexia status and in different performance status. The Chinese version of FAACT scale has good reliability and validity and is suitable for measuring QOL of cachexia patients in Chinese population.

  7. Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1beta -511 single nucleotide polymorphism.

    Science.gov (United States)

    Broekhuizen, Roelinka; Grimble, Robert F; Howell, W Martin; Shale, Dennis J; Creutzberg, Eva C; Wouters, Emiel F; Schols, Annemie M

    2005-11-01

    Cachexia is common in chronic obstructive pulmonary disease (COPD) and is thought to be linked to an enhanced systemic inflammatory response. We investigated differences in the systemic inflammatory profile and polymorphisms in related inflammatory genes in COPD patients. A cross-sectional study was performed in 99 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages II-IV), who were stratified by cachexia based on fat-free mass index (FFMI; in kg/m2: leptin, and urinary pseudouridine (as a marker of cellular protein breakdown) were measured. Fat mass, leptin, and pseudouridine were significantly different (P COPD patients, who are characterized by an elevated systemic inflammatory response, cachexia is not discriminatory for the extent of increase in inflammatory status. This study, however, indicates a potential influence of genetic predisposition on the cachexia process.

  8. Thyroid hormones in conditions of chronic malnutrition. A study with special reference to cancer cachexia

    National Research Council Canada - National Science Library

    Persson, H; Bennegård, K; Lundberg, P A; Svaninger, G; Lundholm, K

    1985-01-01

    ...) and thyroid-hormone binding globulin were related to the nutritional state of patients with cancer cachexia, patients with malnutrition due to other reasons and to well-nourished patients with acute illness...

  9. Cachexia: a preventable comorbidity of cancer. A T.A.R.G.E.T. approach.

    Science.gov (United States)

    Muscaritoli, Maurizio; Molfino, Alessio; Lucia, Simone; Rossi Fanelli, Filippo

    2015-05-01

    Although relevant achievements in the treatment of cancer have been obtained, some barriers still remain in the prevention and treatments of cancer comorbidities, including cachexia. Indeed, the enormous advances in the understanding of the pathogenesis of cancer cachexia have not been paralleled by effective strategies aimed at modifying the cultural approach to this devastating condition. Too little attention is still paid to the nutritional and metabolic changes occurring in cancer, despite their negative effects on patients' tolerance to antineoplastic treatments and outcome. We propose a T.A.R.G.E.T. approach as a novel strategy, encompassing active interventions and research development within the different domains influencing the onset and the progression of cancer cachexia. Moreover, based on the most recent clinical evidences, we suggest that cachexia should be considered a comorbidity of cancer. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Tocilizumab, a proposed therapy for the cachexia of Interleukin6-expressing lung cancer.

    Science.gov (United States)

    Ando, Katsutoshi; Takahashi, Fumiyuki; Kato, Motoyasu; Kaneko, Norihiro; Doi, Tokuhide; Ohe, Yuichiro; Koizumi, Fumiaki; Nishio, Kazuto; Takahashi, Kazuhisa

    2014-01-01

    We previously reported the role of IL-6 in a murine model of cancer cachexia and currently documented a patient in whom tocilizumab, anti-IL-6 receptor antibody, dramatically improved cachexia induced by IL-6 over-expressing lung cancer. Despite this potential to alleviate cancer cachexia, tocilizumab has not been approved for this clinical use. Therefore, preceding our planned clinical trial of tocilizumab, we designed the two studies described here to evaluate the levels of IL-6 in patients with lung cancer and the effect of tocilizumab in a murine model of human cancer cachexia. First, we measured serum IL-6 levels in patients with lung cancer and analyzed its association with cachexia and survival. Next, we examined the effect of a rodent analog of tocilizumab (MR16-1) in the experimental cachexia model. Serum IL-6 levels were higher in patients with cachexia than those without cachexia. In patients with chemotherapy-resistant lung cancer, a high IL-6 serum level correlated strongly with survival, and the cut-off level for affecting their prognosis was 21 pg/mL. Meanwhile, transplantation of IL-6-expressing Lewis Lung Carcinoma cells caused cachexia in mice, which then received either MR16-1 or 0.9% saline. Tumor growth was similar in both groups; however, the MR16-1 group lost less weight, maintained better food and water intake and had milder cachectic features in blood. MR16-1 also prolonged the survival of LLC-IL6 transplanted mice (36.6 vs. 28.5 days, p = 0.016). Our clinical and experimental studies revealed that serum IL-6 is a surrogate marker for evaluating cachexia and the prognosis of patients with chemotherapy resistant metastatic lung cancer and that tocilizumab has the potential of improving prognosis and ameliorating the cachexia that so devastates their quality of life. This outcome greatly encourages our clinical trials to evaluate the safety and efficacy of tocilizumab treatment for patients with increased serum IL-6.

  11. The applicability of a weight loss grading system in cancer cachexia: a longitudinal analysis.

    Science.gov (United States)

    Vagnildhaug, Ola Magne; Blum, David; Wilcock, Andrew; Fayers, Peter; Strasser, Florian; Baracos, Vickie E; Hjermstad, Marianne J; Kaasa, Stein; Laird, Barry; Solheim, Tora S

    2017-10-01

    A body mass index (BMI) adjusted weight loss grading system (WLGS) is related to survival in patients with cancer. The aim of this study was to examine the applicability of the WLGS by confirming its prognostic validity, evaluating its relationship to cachexia domains, and exploring its ability to predict cachexia progression. An international, prospective observational study of patients with incurable cancer was conducted. For each patient, weight loss grade was scored 0-4. Weight loss grade 0 represents a high BMI with limited weight loss, progressing through to weight loss grade 4 representing low BMI and a high degree of weight loss. Survival analyses were used to confirm prognostic validity. Analyses of variance were used to evaluate the relationship between the WLGS and cachexia domains [anorexia, dietary intake, Karnofsky performance status (KPS), and physical and emotional functioning]. Cox regression was used to evaluate if the addition of cachexia domains to the WLGS improved prognostic accuracy. Predictive ability of cachexia progression was assessed by estimating proportion of patients progressing to a more advanced weight loss grade. One thousand four hundred six patients were analysed (median age 66 years; 50% female, 63% KPS ≤ 70). The overall effect of the WLGS on survival was significant as expressed by change in -2 log likelihood (P loss grades ranging from 407 days (95% CI 312-502)-weight loss grade 0 to 119 days (95% CI 93-145)-weight loss grade 4. All cachexia domains significantly deteriorated with increasing weight loss grade, and deterioration was greatest for dietary intake, with a difference corresponding to 0.87 standard deviations between weight loss grades 0 and 4. The addition of KPS, anorexia, and physical and emotional functioning improved the prognostic accuracy of the WLGS. Likelihood of cachexia progression was greater in patients with weight loss grade 2 (39%) than that with weight loss grade 0 (19%) or 1 (22%). The WLGS is

  12. Potential Biomarkers of Fat Loss as a Feature of Cancer Cachexia

    OpenAIRE

    Maryam Ebadi; Mazurak, Vera C.

    2015-01-01

    Fat loss is associated with shorter survival and reduced quality of life in cancer patients. Effective intervention for fat loss in cachexia requires identification of the condition using prognostic biomarkers for early detection and prevention of further depletion. No biomarkers of fat mass alterations have been defined for application to the neoplastic state. Several inflammatory cytokines have been implicated in mediating fat loss associated with cachexia; however, plasma levels may no...

  13. Bioelectrical impedance analysis for diagnosing sarcopenia and cachexia: what are we really estimating?

    Science.gov (United States)

    Gonzalez, Maria Cristina; Heymsfield, Steven B

    2017-04-01

    As reference methods are not available for identifying low skeletal muscle mass in clinical practice, the European Group on Sarcopenia in Older People the Asian Working Group for Sarcopenia and the International Consensus for Cancer Cachexia guidelines accept bioelectrical impedance analysis (BIA) as an option for sarcopenia and cachexia assessment. Using different BIA equations, several components that represent 'muscularity' can be assessed. Total skeletal muscle mass or appendicular skeletal muscle mass normalized in relation to height (skeletal muscle mass index or appendicular skeletal muscle index, respectively) is the most common term used in the consensus. These terms are similar, but they should not be used as synonymous. Both terms can be used to define sarcopenia, but adequate equations and cut-off values should be used according to the studied population. However, there is a disagreement between the sarcopenia definition assessed by using BIA from the European Group on Sarcopenia in Older People and Cachexia Consensus, and this can lead to an overestimation of sarcopenia and, consequently, cachexia. An effort should be made to standardize the terminology employed by the Societies to define low muscularity and sarcopenia by using BIA. Future validation studies may show the need for specific cut-off values for each population using this method. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  14. Cachexia in children with chronic kidney disease: challenges in diagnosis and treatment.

    Science.gov (United States)

    Mak, Robert H

    2016-12-01

    Although cachexia is highly prevalent in adult patients with chronic kidney disease (CKD), it is understudied and less well characterized in children. Recent evidence suggests that cachexia is also prevalent in children with CKD but presents challenges in diagnosis and treatment. A study from the CKD in children cohort showed that CKD cachexia or protein-energy wasting, using modified pediatric diagnostic criteria, such as lack of expected weight gain instead of weight loss and BMI for height age, had a prevalence of 7-20%. When growth indices such as height SD score (SDS)/height velocity SDS was included in the criteria, cachexia or PEW correlated with the morbidity outcome of increased hospitalization risk in children with CKD. Conversely, aggressive nutritional supplementation in children with advanced CKD, with nasogastric or gastric tube feeding, led to prevalence of obesity over that of cachexia. Body habitus of underweight and obesity have been shown to be associated with the worst clinical outcomes in both adults and children with CKD. Optimal nutritional therapy remains the mainstay of treatment of cachexia in CKD children with therapeutic goals of maintaining BMI as well as linear growth within the normal range.

  15. Prevalence of cachexia in chronic heart failure and characteristics of body composition and metabolic status

    DEFF Research Database (Denmark)

    Christensen, Heidi Marie; Kistorp, Caroline Michaela Nervil; Schou, Morten

    2012-01-01

    The prevalence of cardiac cachexia has previously been estimated to 8-42 %. However, novel treatment strategies for chronic heart failure (CHF) have improved and decreased morbidity and mortality. Therefore, we aimed to reassess the prevalence of cachexia in an outpatient CHF clinic...... and to characterize a CHF population with and without cachexia with respect to body composition and related biomarkers. From 2008 to 2011, we screened 238 optimally treated, non-diabetic CHF patients for cardiac cachexia, defined as unintentional non-oedematous weight loss of >5 % over ≥6 months. CHF patients (LVEF...... 45 % (n = 19). The groups were matched for age, sex, and kidney function. Body composition was assessed by dual energy X-ray absorptiometry. The prevalence of cachexia was 10.5 %. Abdominal fat ± SD (%) was reduced in cachectic CHF: 27.4 ± 10.0 versus 37.5 ± 10.6 % (CHF, no cachexia) and 40...

  16. [The Nutritional Care Experience of a Post-Operative Periampullary Cancer Patient With Cachexia].

    Science.gov (United States)

    Liou, Yan-Ting; Chiang, Pin-Yi; Shun, Shiow-Ching

    2016-04-01

    Cachexia is one of the most widely overlooked of the syndromes that are experienced by cancer patients. This syndrome is especially prevalent among patients with gastroenterology tract cancer. Although the National Comprehensive Cancer Network (NCCN) issued palliative-care practice guidelines for cachexia in 2015, guidelines have yet to be issued for the clinical setting. The authors reviewed the literature and applied their clinical experience to create an approach for identifying the degree of cachexia in a post-operative patient with periampullary cancer. This approach assesses the nutritional status, physical status, laboratory results, and gastrointestinal system functions of the patient using the Cachexia Assessment Scale (CAS) and NCCN Practice Guidelines for Cachexia. The patient improved under nursing care with an increase in nutritional intake and physical activity facilitating their process of post-surgical physical recovery. The authors hope that this experience using the combined CAS-NCCN Practice Guidelines will help clinical caregivers better understand how to apply the relevant guidelines in clinical settings. The developed approach may help nurses assess the comprehensive nutrition status of patients and related factors in order to provide interventions that will decrease the progression of cachexia effectively and promote quality of life.

  17. Pyrrolidine Dithiocarbamate (PDTC Attenuates Cancer Cachexia by Affecting Muscle Atrophy and Fat Lipolysis

    Directory of Open Access Journals (Sweden)

    Chunxiao Miao

    2017-12-01

    Full Text Available Cancer cachexia is a kind of whole body metabolic disorder syndrome accompanied with severe wasting of muscle and adipose tissue. NF-κB signaling plays an important role during skeletal muscle atrophy and fat lipolysis. As an inhibitor of NF-κB signaling, Pyrrolidine dithiocarbamate (PDTC was reported to relieve cancer cachexia; however, its mechanism remains largely unknown. In our study, we showed that PDTC attenuated cancer cachexia symptom in C26 tumor bearing mice models in vivo without influencing tumor volume. What’s more, PDTC inhibited muscle atrophy and lipolysis in cells models in vitro induced by TNFα and C26 tumor medium. PDTC suppressed atrophy of myotubes differentiated from C2C12 by reducing MyoD and upregulating MuRF1, and preserving the expression of perilipin as well as blocking the activation of HSL in 3T3-L1 mature adipocytes. Meaningfully, we observed that PDTC also inhibited p38 MAPK signaling besides the NF-κB signaling in cancer cachexia in vitro models. In addition, PDTC also influenced the protein synthesis of skeletal muscle by activating AKT signaling and regulated fat energy metabolism by inhibiting AMPK signaling. Therefore, PDTC primarily influenced different pathways in different tissues. The study not only established a simple and reliable screening drugs model of cancer cachexia in vitro but also provided new theoretical basis for future treatment of cancer cachexia.

  18. White adipose tissue IFN-γ expression and signalling along the progression of rodent cancer cachexia.

    Science.gov (United States)

    Yamashita, Alex Shimura; das Neves, Rodrigo Xavier; Rosa-Neto, José Cesar; Lira, Fábio Dos Santos; Batista, Miguel Luís; Alcantara, Paulo Sérgio; Otoch, José Pinhata; Seelaender, Marília

    2017-01-01

    Cachexia is associated with increased morbidity and mortality in cancer. The White adipose tissue (WAT) synthesizes and releases several pro-inflammatory cytokines that play a role in cancer cachexia-related systemic inflammation. IFN-γ is a pleiotropic cytokine that regulates several immune and metabolic functions. To assess whether IFN-γ signalling in different WAT pads is modified along cancer-cachexia progression, we evaluated IFN-γ receptors expression (IFNGR1 and IFNGR2) and IFN-γ protein expression in a rodent model of cachexia (7, 10, and 14days after tumour implantation). IFN-γ protein expression was heterogeneously modulated in WAT, with increases in the mesenteric pad and decreased levels in the retroperitoneal depot along cachexia progression. Ifngr1 was up-regulated 7days after tumour cell injection in mesenteric and epididymal WAT, but the retroperitoneal depot showed reduced Ifngr1 gene expression. Ifngr2 gene expression was increased 7 and 14days after tumour inoculation in mesenteric WAT. The results provide evidence that changes in IFN-γ expression and signalling may be perceived at stages preceding refractory cachexia, and therefore, might be employed as a means to assess the early stage of the syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. TNF-α and cancer cachexia: Molecular insights and clinical implications.

    Science.gov (United States)

    Patel, Hetal J; Patel, Bhoomika M

    2017-02-01

    Cancer cachexia characterized by a chronic wasting syndrome, involves skeletal muscle loss and adipose tissue loss and resistance to conventional nutritional support. Cachexia is responsible for the reduction in quality and length of life of cancer patients. It also decreases the muscle strength of the patients. The pro-inflammatory and pro-cachectic factors produced by the tumor cells have important role in genesis of cachexia. A number of pro-inflammatory cytokines, like interleukin-1 (IL-1), IL-6, tumor necrosis factor- alpha (TNF-α) may have important role in the pathological mechanisms of cachexia in cancer. Particularly, TNF-α has a direct catabolic effect on skeletal muscle and causes wasting of muscle by the induction of the ubiquitin-proteasome system (UPS). In cancer cachexia condition, there is alteration in carbohydrate, protein and fat metabolism. TNF-α is responsible for the increase in gluconeogenesis, loss of adipose tissue and proteolysis, while causing decrease in protein, lipid and glycogen synthesis. It has been associated with the formation of IL-1 and increases the uncoupling protein-2 (UCP2) and UCP3 expression in skeletal muscle in cachectic state. The main aim of the present review is to evaluate and discuss the role of TNF-α in different metabolic alterations and muscle wasting in cancer cachexia. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The regulation of skeletal muscle protein turnover during the progression of cancer cachexia in the Apc(Min/+ mouse.

    Directory of Open Access Journals (Sweden)

    James P White

    Full Text Available Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The Apc(Min/+ mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the Apc(Min/+ mouse is not known. Cachexia progression was studied in Apc(Min/+ mice that were either weight stable (WS or had initial (≤5%, intermediate (6-19%, or extreme (≥20% body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172, AMPK activity, and raptor phosphorylation (Ser 792 were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process.

  1. Expression of CCAAT/Enhancer Binding Protein Beta in Muscle Satellite Cells Inhibits Myogenesis in Cancer Cachexia

    OpenAIRE

    François Marchildon; Émilie Lamarche; Neena Lala-Tabbert; Catherine St-Louis; Nadine Wiper-Bergeron

    2015-01-01

    Cancer cachexia is a paraneoplastic syndrome that causes profound weight loss and muscle mass atrophy and is estimated to be the cause of up to 30% of cancer deaths. Though the exact cause is unknown, patients with cancer cachexia have increased muscle protein catabolism. In healthy muscle, injury activates skeletal muscle stem cells, called satellite cells, to differentiate and promote regeneration. Here, we provide evidence that this mechanism is inhibited in cancer cachexia due to persiste...

  2. The Regulation of Skeletal Muscle Protein Turnover during the Progression of Cancer Cachexia in the ApcMin/+ Mouse

    Science.gov (United States)

    White, James P.; Baynes, John W.; Welle, Stephen L.; Kostek, Matthew C.; Matesic, Lydia E.; Sato, Shuichi; Carson, James A.

    2011-01-01

    Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The ApcMin/+ mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the ApcMin/+ mouse is not known. Cachexia progression was studied in ApcMin/+ mice that were either weight stable (WS) or had initial (≤5%), intermediate (6–19%), or extreme (≥20%) body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172), AMPK activity, and raptor phosphorylation (Ser 792) were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process. PMID:21949739

  3. Sarcopenia and cachexia evaluation in different healthcare settings: a questionnaire survey of health professionals.

    Science.gov (United States)

    Nakahara, Saori; Wakabayashi, Hidetaka; Maeda, Keisuke; Nishioka, Shinta; Kokura, Yoji

    2018-01-01

    The rates of sarcopenia and cachexia evaluations by different occupational groups at different settings are unclear. The objectives are to evaluate and compare the relative use of sarcopenia and cachexia evaluations among dietitians and associated healthcare professionals in a diverse range of settings. Participants were 4,621 members from the Japanese Association of Rehabilitation Nutrition. Settings included acute general wards, convalescent rehabilitation wards, long-term care wards, homecare service, and other settings. A questionnaire-based cross-sectional study was performed to evaluate assessments for sarcopenia and cachexia among dietitians and other professionals. Multiple comparisons based on Bonferroni method and logistic regression analysis were used. 718 (15.5%) answered the questionnaire. Data from 683 valid questionnaires were analyzed. Muscle strength, muscle mass, physical function, and cachexia were assessed by 53.4%, 51.1%, 53.4%, and 17.4% of dietitians. At convalescent rehabilitation wards, these rates were 81.8%, 62.0%, 82.5%, and 14.0%. The use of muscle strength and physical function evaluations was significantly lower among dietitians than among physical therapists and occupational therapists. The use of muscle mass and cachexia evaluations was not significantly different among the occupations. The use of muscle mass and strength evaluations was significantly higher in convalescent rehabilitation wards than in acute general wards, long-term care wards and facilities, and other settings, but not in homecare services. Cachexia evaluations were not significantly different between all settings. Raising the awareness of cachexia and sarcopenia among dietitians is a key issue, which should be addressed.

  4. Establishment and characterization of a novel murine model of pancreatic cancer cachexia

    Science.gov (United States)

    Michaelis, Katherine A.; Zhu, Xinxia; Burfeind, Kevin G.; Krasnow, Stephanie M.; Levasseur, Peter R.; Morgan, Terry K.

    2017-01-01

    Abstract Background Cachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) is one of the most important conditions associated with cachexia, with >80% of PDAC patients suffering from the condition. To establish the cardinal features of a murine model of PDAC‐associated cachexia, we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRASG12D P53R172H Pdx‐Cre+/+ (KPC) mouse. Methods Male and female C57BL/6 mice were inoculated subcutaneously, intraperitoneally, or orthotopically with KPC tumour cells. We performed rigorous phenotypic, metabolic, and behavioural analysis of animals over the course of tumour development. Results All routes of administration produced rapidly growing tumours histologically consistent with moderate to poorly differentiated PDAC. The phenotype of this model was dependent on route of administration, with orthotopic and intraperitoneal implantation inducing more severe cachexia than subcutaneous implantation. KPC tumour growth decreased food intake, decreased adiposity and lean body mass, and decreased locomotor activity. Muscle catabolism was observed in both skeletal and cardiac muscles, but the dominant catabolic pathway differed between these tissues. The wasting syndrome in this model was accompanied by hypothalamic inflammation, progressively decreasing brown and white adipose tissue uncoupling protein 1 (Ucp1) expression, and increased peripheral inflammation. Haematological and endocrine abnormalities included neutrophil‐dominant leukocytosis and anaemia, and decreased serum testosterone. Conclusions Syngeneic KPC allografts are a robust model for studying cachexia, which recapitulate key features of the PDAC disease process and induce a wide array of cachexia manifestations. This model is therefore ideally suited for future studies exploring the physiological systems involved in cachexia and for preclinical

  5. Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia

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    Benny Klimek, Margaret E.; Aydogdu, Tufan [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Link, Majik J.; Pons, Marianne [Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Koniaris, Leonidas G. [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology and Experimental Therapeutics Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL (United States); Zimmers, Teresa A., E-mail: tzimmers@med.miami.edu [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology and Experimental Therapeutics Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL (United States)

    2010-01-15

    Cachexia, progressive loss of fat and muscle mass despite adequate nutrition, is a devastating complication of cancer associated with poor quality of life and increased mortality. Myostatin is a potent tonic muscle growth inhibitor. We tested how myostatin inhibition might influence cancer cachexia using genetic and pharmacological approaches. First, hypermuscular myostatin null mice were injected with Lewis lung carcinoma or B16F10 melanoma cells. Myostatin null mice were more sensitive to tumor-induced cachexia, losing more absolute mass and proportionately more muscle mass than wild-type mice. Because myostatin null mice lack expression from development, however, we also sought to manipulate myostatin acutely. The histone deacetylase inhibitor Trichostatin A has been shown to increase muscle mass in normal and dystrophic mice by inducing the myostatin inhibitor, follistatin. Although Trichostatin A administration induced muscle growth in normal mice, it failed to preserve muscle in colon-26 cancer cachexia. Finally we sought to inhibit myostatin and related ligands by administration of the Activin receptor extracellular domain/Fc fusion protein, ACVR2B-Fc. Systemic administration of ACVR2B-Fc potently inhibited muscle wasting and protected adipose stores in both colon-26 and Lewis lung carcinoma cachexia, without affecting tumor growth. Enhanced cachexia in myostatin knockouts indicates that host-derived myostatin is not the sole mediator of muscle wasting in cancer. More importantly, skeletal muscle preservation with ACVR2B-Fc establishes that targeting myostatin-family ligands using ACVR2B-Fc or related molecules is an important and potent therapeutic avenue in cancer cachexia.

  6. [Melatonin as a marker of the grade of cardiac disorders during cachexia development in oncological patients of different ages].

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    Ballyuzek, M F; Mashkova, M V; Arutjunyan, A V; Duke, V A

    2017-01-01

    We have examined 103 patients at the age from 28 to 78 with the newly diagnosed oncological disease at stages II-IV before the beginning of anticancer treatment. The identification of the signs of the cachexia syndrome and its stage (pre-cachexia, cachexia) were carried out in the accordance with the CASCO criteria (2011) and taking into the account the age of the patients. The cardiovascular infringements were found to be comorbid to the oncological disease significantly more often in patients with signs of cachexia syndrome on the pre-cachexia stage and the total index of cardiovascular disorders in oncological patients increases with the severity of cachexia. In the course of the cachexia symptoms development the significant decline of melatonin excretion level (evaluated by the excretion of its main metabolite 6-sulfatoximelatonin level - aMT6s) in oncological patients was noted. The lowest changes in aMT6s levels were observed in patients older than 60 years, referred to the group of pre-cachexia, which may indicate the heterogeneity of the investigated groups as a result of the combination of manifestations of geriatric syndromes and cancer pathology. The possibility of false-positive diagnosis of pre-cachexia due to a combination of polygenic metabolic and age-related changes in elderly patients should be taken into account. Therefore, evaluation of melatonin excretion can be recommended as an additional marker in diagnosis and differential diagnosis of cachexia syndrome particularly in geriatric patients. A significant correlation between the occurrence and/or worsening of cardiac disease in cancer patients, cachexia symptoms and reduced level of aMT6s were revealed.

  7. Cancer anorexia-cachexia syndrome: are neuropeptides the key?

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    Inui, A

    1999-09-15

    Progressive wasting is common in many types of cancer and is one of the most important factors leading to early death in cancer patients. Weight loss is a potent stimulus to food intake in normal humans and animals. The persistence of anorexia in cancer patients, therefore, implies a failure of this adaptive feeding response, although the weight loss in the patients differs from that found in simple starvation. Tremendous progress has been made in the last 5 years with regard to the regulation of feeding and body weight. It has been demonstrated that leptin, a hormone secreted by adipose tissue, is an integral component of the homeostatic loop of body weight regulation. Leptin acts to control food intake and energy expenditure via neuropeptidergic effector molecules within the hypothalamus. Complex interactions among the nervous, endocrine, and immune systems affect the loop and induce behavioral and metabolic responses. A number of cytokines, including tumor necrosis factor-alpha, interleukins 1 and 6, IFN-gamma, leukemia inhibitory factor, and ciliary neurotrophic factor have been proposed as mediators of the cachectic process. Cytokines may play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin. This could be done by persistent stimulation of anorexigenic neuropeptides such as corticotropin-releasing factor, as well as by inhibition of the neuropeptide Y orexigenic network that consists of opioid peptides and galanin, in addition to the newly identified melanin-concentrating hormone, orexin, and agouti-related peptide. Information is being gathered, although it is still insufficient, on such abnormalities in the hypothalamic neuropeptide circuitry in tumor-bearing animals that coincide with the development of anorexia and cachexia. Characterization of the feeding-associated gene products have revealed new biochemical pathways and molecular targets for pharmacological

  8. Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R in cancer cachexia

    Directory of Open Access Journals (Sweden)

    Scherag André

    2008-03-01

    Full Text Available Abstract Background At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (MC4R in the development of cancer cachexia. In humans, MC4R mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2% was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele. Methods BMI (body mass index in kg/m2 of 509 patients (295 males with malignant neoplasms was determined; additionally patients were asked about premorbid/pretherapeutical changes of appetite and weight loss. Cachexia was defined as a weight loss of at least 5% prior to initiation of therapy; to fulfil this criterion this weight loss had to occur independently of other plausible reasons; in single cases weight loss was the initial reason for seeing a physician. The average age in years (± SD was 59.0 ± 14.5 (males: 58.8 ± 14.0, females 59.2 ± 14.0. Blood samples were taken for genotyping of the Val103Ile by PCR- RFLP. Results Most of the patients suffered from lymphoma, leukaemia and gastrointestinal tumours. 107 of the patients (21% fulfilled our criteria for cancer cachexia. We did not detect association between the Val103Ile polymorphism and cancer cachexia. However, if we exploratively excluded the patients with early leucaemic stages, we detected a trend towards the opposite effect (p 0.39. Conclusion Heterozygotes for the 103Ile-allele are not more prone to develop cancer cachexia than patients without this allele; possibly, Ile103 carriers might be more resistant to cancer cachexia in patients with solid tumors. Further studies of the melanocortinergic system in cachexia of

  9. Cancer cachexia and diabetes: similarities in metabolic alterations and possible treatment.

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    Chevalier, Stéphanie; Farsijani, Samaneh

    2014-06-01

    Cancer cachexia is a metabolic syndrome featuring many alterations typical of type 2 diabetes (T2D). While muscle wasting is a hallmark of cachexia, epidemiological evidence also supports an accelerated age-related muscle loss in T2D. Insulin resistance manifests in both conditions and impairs glucose disposal and protein anabolism by tissues. A greater contribution of gluconeogenesis to glucose production may limit amino acid availability for muscle protein synthesis, further aggravating muscle loss. In the context of inter-dependence between glucose and protein metabolism, the present review summarizes the current state of knowledge on alterations that may lead to muscle wasting in human cancer. By highlighting the similarities with T2D, a disease that has been more extensively studied, the objective of this review is to provide a better understanding of the pathophysiology of cancer cachexia and to consider potential treatments usually targeted for T2D. Nutritional approaches aimed at stimulating protein anabolism might include specially formulated food with optimal protein and amino acid composition. Because the gradual muscle loss in T2D may be attenuated by diabetes treatment, anti-diabetic drugs might be considered in cachexia treatment. Metformin emerges as a choice candidate as it acts both on reducing gluconeogenesis and improving insulin sensitivity, and has demonstrated tumour suppressor properties in multiple cancer types. Such a multimodal approach to slow or reverse muscle wasting in cachexia warrants further investigation.

  10. Cachexia at diagnosis is associated with poor survival in head and neck cancer patients.

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    Orell-Kotikangas, Helena; Österlund, Pia; Mäkitie, Outi; Saarilahti, Kauko; Ravasco, Paula; Schwab, Ursula; Mäkitie, Antti A

    2017-07-01

    One third of the patients had cachexia with an association of significantly shorter survival. These results suggest that combining HGS and MAMA seems to be a practical method to screen cachexia in patients with head and neck cancer and may also be used when assessing their prognosis. The aim of this study was to analyze the hypothesis that cachexia defined as both low mid-arm muscle area (MAMA) and handgrip strength (HGS) is associated with decreased survival in patients with head and neck squamous cell carcinoma (HNSCC). Sixty-five consecutive patients with primary HNSCC were enrolled prior to cancer therapy. Cachexia was defined as low handgrip strength (HGS) and low mid-arm muscle area (MAMA). Nutritional status was assessed by patient-generated subjective global assessment (PG-SGA) and sarcopenia by low MAMA. Biochemical parameters reflecting nutritional status and S-25-OHD were measured. Cachexia was seen in 31% and sarcopenia in 46% of patients. Altogether, 34% of patients were malnourished. Disease-free survival was 13 months (3-62) in cachectic patients, compared with 66 months (31-78) in non-cachectic patients (p = 0.009). S-25-OHD was 28 nmol/l in cachectic patients, compared with 46 nmol/l in non-cachectic patients (p = 0.009) and prealbumin 187 mg/l and 269 mg/l, respectively (p < 0.001).

  11. Resistance Exercise Reduces Skeletal Muscle Cachexia and Improves Muscle Function in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Salaheddin Sharif

    2011-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic, systemic, autoimmune, inflammatory disease associated with cachexia (reduced muscle and increased fat. Although strength-training exercise has been used in persons with RA, it is not clear if it is effective for reducing cachexia. A 46-year-old woman was studied to determine: (i if resistance exercise could reverse cachexia by improving muscle mass, fiber cross-sectional area, and muscle function; and (2 if elevated apoptotic signaling was involved in cachexia with RA and could be reduced by resistance training. A needle biopsy was obtained from the vastus lateralis muscle of the RA subject before and after 16 weeks of resistance training. Knee extensor strength increased by 13.6% and fatigue decreased by 2.8% Muscle mass increased by 2.1%. Average muscle fiber cross-sectional area increased by 49.7%, and muscle nuclei increased slightly after strength training from 0.08 to 0.12 nuclei/μm2. In addition, there was a slight decrease (1.6% in the number of apoptotic muscle nuclei after resistance training. This case study suggests that resistance training may be a good tool for increasing the number of nuclei per fiber area, decreasing apoptotic nuclei, and inducing fiber hypertrophy in persons with RA, thereby slowing or reversing rheumatoid cachexia.

  12. Impact of a multidisciplinary rehabilitation nutrition team on evaluating sarcopenia, cachexia and practice of rehabilitation nutrition.

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    Kokura, Yoji; Wakabayashi, Hidetaka; Maeda, Keisuke; Nishioka, Shinta; Nakahara, Saori

    2017-01-01

    To determine whether the presence of a multidisciplinary rehabilitation nutrition team affects sarcopenia and cachexia evaluation and practice of rehabilitation nutrition. A cross-sectional study using online questionnaire among members of the Japanese Association of Rehabilitation Nutrition (JARN) was conducted. Questions were related to sarcopenia and cachexia evaluation and practice of rehabilitation nutrition. 677 (14.7%) questionnaires were analysed. 44.5% reported that their institution employed a rehabilitation nutrition team, 20.2% conducted rehabilitation nutrition rounds and 26.1% conducted rehabilitation nutrition meetings. A total of 51.7%, 69.7%, 69.0% and 17.8% measured muscle mass, muscle strength, physical function and cachexia, respectively. For those with a rehabilitation nutrition team, 63.5%, 80.7%, 82.4% and 22.9% measured muscle mass, muscle strength, physical function and cachexia, respectively, whereas 46.7%, 78.0% and 78.1% of the respondents reported implementation of nutrition planning strategies in consideration of energy accumulation, rehabilitation training in consideration of nutritional status and use of dietary supplements, respectively. Multivariate logistic regression analysis showed that the use of a rehabilitation nutrition team independently affected sarcopenia evaluation and practice of rehabilitation nutrition but not cachexia evaluation. The presence of a multidisciplinary rehabilitation nutrition team increased the frequency of sarcopenia evaluation and practice of rehabilitation nutrition. J. Med. Invest. 64: 140-145, February, 2017.

  13. PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.

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    Kir, Serkan; Komaba, Hirotaka; Garcia, Ana P; Economopoulos, Konstantinos P; Liu, Wei; Lanske, Beate; Hodin, Richard A; Spiegelman, Bruce M

    2016-02-09

    Cachexia is a wasting syndrome associated with elevated basal energy expenditure and loss of adipose and muscle tissues. It accompanies many chronic diseases including renal failure and cancer and is an important risk factor for mortality. Our recent work demonstrated that tumor-derived PTHrP drives adipose tissue browning and cachexia. Here, we show that PTH is involved in stimulating a thermogenic gene program in 5/6 nephrectomized mice that suffer from cachexia. Fat-specific knockout of PTHR blocked adipose browning and wasting. Surprisingly, loss of PTHR in fat tissue also preserved muscle mass and improved muscle strength. Similarly, PTHR knockout mice were resistant to cachexia driven by tumors. Our results demonstrate that PTHrP and PTH mediate wasting through a common mechanism involving PTHR, and there exists an unexpected crosstalk mechanism between wasting of fat tissue and skeletal muscle. Targeting the PTH/PTHrP pathway may have therapeutic uses in humans with cachexia. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. A non-human primate model of radiation-induced cachexia.

    Science.gov (United States)

    Cui, Wanchang; Bennett, Alexander W; Zhang, Pei; Barrow, Kory R; Kearney, Sean R; Hankey, Kim G; Taylor-Howell, Cheryl; Gibbs, Allison M; Smith, Cassandra P; MacVittie, Thomas J

    2016-03-31

    Cachexia, or muscle wasting, is a serious health threat to victims of radiological accidents or patients receiving radiotherapy. Here, we propose a non-human primate (NHP) radiation-induced cachexia model based on clinical and molecular pathology findings. NHP exposed to potentially lethal partial-body irradiation developed symptoms of cachexia such as body weight loss in a time- and dose-dependent manner. Severe body weight loss as high as 20-25% was observed which was refractory to nutritional intervention. Radiographic imaging indicated that cachectic NHP lost as much as 50% of skeletal muscle. Histological analysis of muscle tissues showed abnormalities such as presence of central nuclei, inflammation, fatty replacement of skeletal muscle, and muscle fiber degeneration. Biochemical parameters such as hemoglobin and albumin levels decreased after radiation exposure. Levels of FBXO32 (Atrogin-1), ActRIIB and myostatin were significantly changed in the irradiated cachectic NHP compared to the non-irradiated NHP. Our data suggest NHP that have been exposed to high dose radiation manifest cachexia-like symptoms in a time- and dose-dependent manner. This model provides a unique opportunity to study the mechanism of radiation-induced cachexia and will aid in efficacy studies of mitigators of this disease.

  15. F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities.

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    Sukari, Ammar; Muqbil, Irfana; Mohammad, Ramzi M; Philip, Philip A; Azmi, Asfar S

    2016-02-01

    Cancer cachexia is a debilitating metabolic syndrome accounting for fatigue, an impairment of normal activities, loss of muscle mass associated with body weight loss eventually leading to death in majority of patients with advanced disease. Cachexia patients undergoing skeletal muscle atrophy show consistent activation of the SCF ubiquitin ligase (F-BOX) family member Atrogin-1 (also known as MAFBx/FBXO32) alongside the activation of the muscle ring finger protein1 (MuRF1). Other lesser known F-BOX family members are also emerging as key players supporting muscle wasting pathways. Recent work highlights a spectrum of different cancer signaling mechanisms impacting F-BOX family members that feed forward muscle atrophy related genes during cachexia. These novel players provide unique opportunities to block cachexia induced skeletal muscle atrophy by therapeutically targeting the SCF protein ligases. Conversely, strategies that induce the production of proteins may be helpful to counter the effects of these F-BOX proteins. Through this review, we bring forward some novel targets that promote atrogin-1 signaling in cachexia and muscle wasting and highlight newer therapeutic opportunities that can help in the better management of patients with this devastating and fatal disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Mechanisms of anorexia-cachexia syndrome and rational for treatment with selective ghrelin receptor agonist.

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    Esposito, Angela; Criscitiello, Carmen; Gelao, Lucia; Pravettoni, Gabriella; Locatelli, Marzia; Minchella, Ida; Di Leo, Maria; Liuzzi, Rita; Milani, Alessandra; Massaro, Mariangela; Curigliano, Giuseppe

    2015-11-01

    Cancer cachexia is a multi-organ, multifactorial and often irreversible syndrome affecting many patients with cancer. Cancer cachexia is invariably associated with weight loss, mainly from loss of skeletal muscle and body fat, conditioning a reduced quality of life due to asthenia, anorexia, anaemia and fatigue. Treatment options for treating cancer cachexia are limited. The approach is multimodal and may include: treatment of secondary gastrointestinal symptoms, nutritional treatments, drug, and non-drug treatments. Nutritional counselling and physical training may be beneficial in delaying or preventing the development of anorexia-cachexia. However, these interventions are limited in their effect, and no definitive pharmacological treatment is available to address the relevant components of the syndrome. Anamorelin is a first-in-class, orally active ghrelin receptor agonist that binds and stimulates the growth hormone secretagogue receptor centrally, thereby mimicking the appetite-enhancing and anabolic effects of ghrelin. It represents a new class of drug and an additional treatment option for this patient group, whose therapeutic options are currently limited. In this review we examine the mechanisms of anamorelin by which it contrasts catabolic states, its role in regulation of metabolism and energy homeostasis, the data of recent trials in the setting of cancer cachexia and its safety profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Effect of Sipjeondaebo-Tang on Cancer-Induced Anorexia and Cachexia in CT-26 Tumor-Bearing Mice

    Science.gov (United States)

    Jung, Ki Yong; Woo, Sang-Mi; Jun, Chan-Yong; Park, Jong Hyeong; Shin, Yong Cheol; Ko, Seong-Gyu

    2014-01-01

    Cancer-associated anorexia and cachexia are a multifactorial condition described by a loss of body weight and muscle with anorexia, asthenia, and anemia. Moreover, they correlate with a high mortality rate, poor response to chemotherapy, poor performance status, and poor quality of life. Cancer cachexia is regulated by proinflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α). In addition, glucagon like peptide-1 (GIP-1), peptide YY (PYY), ghrelin, and leptin plays a crucial role in food intake. In this study, we investigated the therapeutic effects of one of the traditional herbal medicines, Sipjeondaebo-tang (Juzen-taiho-to in Japanese; SJDBT), on cancer anorexia and cachexia in a fundamental mouse cancer anorexia/cachexia model, CT-26 tumor-bearing mice. SJDBT was more significantly effective in a treatment model where it was treated after anorexia and cachexia than in a prevention model where it was treated before anorexia and cachexia on the basis of parameters such as weights of muscles and whole body and food intakes. Moreover, SJDBT inhibited a production of IL-6, MCP-1, PYY, and GLP-1 and ameliorated cancer-induced anemia. Therefore, our in vivo studies provide evidence on the role of SJDBT in cancer-associated anorexia and cachexia, thereby suggesting that SJDBT may be useful for treating cancer-associated anorexia and cachexia. PMID:24963216

  18. Effect of Sipjeondaebo-tang on cancer-induced anorexia and cachexia in CT-26 tumor-bearing mice.

    Science.gov (United States)

    Choi, Youn Kyung; Jung, Ki Yong; Woo, Sang-Mi; Yun, Yee Jin; Jun, Chan-Yong; Park, Jong Hyeong; Shin, Yong Cheol; Cho, Sung-Gook; Ko, Seong-Gyu

    2014-01-01

    Cancer-associated anorexia and cachexia are a multifactorial condition described by a loss of body weight and muscle with anorexia, asthenia, and anemia. Moreover, they correlate with a high mortality rate, poor response to chemotherapy, poor performance status, and poor quality of life. Cancer cachexia is regulated by proinflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor- α (TNF- α). In addition, glucagon like peptide-1 (GIP-1), peptide YY (PYY), ghrelin, and leptin plays a crucial role in food intake. In this study, we investigated the therapeutic effects of one of the traditional herbal medicines, Sipjeondaebo-tang (Juzen-taiho-to in Japanese; SJDBT), on cancer anorexia and cachexia in a fundamental mouse cancer anorexia/cachexia model, CT-26 tumor-bearing mice. SJDBT was more significantly effective in a treatment model where it was treated after anorexia and cachexia than in a prevention model where it was treated before anorexia and cachexia on the basis of parameters such as weights of muscles and whole body and food intakes. Moreover, SJDBT inhibited a production of IL-6, MCP-1, PYY, and GLP-1 and ameliorated cancer-induced anemia. Therefore, our in vivo studies provide evidence on the role of SJDBT in cancer-associated anorexia and cachexia, thereby suggesting that SJDBT may be useful for treating cancer-associated anorexia and cachexia.

  19. The role of hypothalamic inflammation, the hypothalamic–pituitary–adrenal axis and serotonin in the cancer anorexia–cachexia syndrome

    NARCIS (Netherlands)

    Norren, van Klaske; Dwarkasing, Jvalini T.; Witkamp, Renger F.

    2017-01-01

    PURPOSE OF REVIEW: In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia–cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key

  20. Pathophysiology of anorexia in the cancer cachexia syndrome

    Science.gov (United States)

    Ezeoke, Chukwuemeka Charles; Morley, John E

    2015-01-01

    Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients. PMID:26675762

  1. Cancer cachexia update in head and neck cancer: Pathophysiology and treatment.

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    Couch, Marion E; Dittus, Kim; Toth, Michael J; Willis, Monte S; Guttridge, Denis C; George, Jonathan R; Chang, Eric Y; Gourin, Christine G; Der-Torossian, Hirak

    2015-07-01

    The pathophysiology of cancer cachexia remains complex. A comprehensive literature search was performed up to April 2013 using PubMed, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and the Google search engine. In this review, we focus on the different mediators of impaired anabolism and upregulated catabolism that alter the skeletal muscle homeostasis resulting in the wasting of cancer cachexia. We present recent evidence of targeted treatment modalities from clinical trials along with their potential mechanisms of action. We also report on the most current evidence from randomized clinical trials using multimodal treatments in patients with cancer cachexia, but also the evidence from head and neck cancer-specific trials. A more complete understanding of the pathophysiology of the syndrome may lead to more effective targeted therapies and improved outcomes for patients. © 2015 Wiley Periodicals, Inc.

  2. Potential Biomarkers of Fat Loss as a Feature of Cancer Cachexia.

    Science.gov (United States)

    Ebadi, Maryam; Mazurak, Vera C

    2015-01-01

    Fat loss is associated with shorter survival and reduced quality of life in cancer patients. Effective intervention for fat loss in cachexia requires identification of the condition using prognostic biomarkers for early detection and prevention of further depletion. No biomarkers of fat mass alterations have been defined for application to the neoplastic state. Several inflammatory cytokines have been implicated in mediating fat loss associated with cachexia; however, plasma levels may not relate to adipose atrophy. Zinc-α2-glycoprotein may be a local catabolic mediator within adipose tissue rather than serving as a plasma biomarker of fat loss. Plasma glycerol and leptin associate with adipose tissue atrophy and mass, respectively; however, no study has evaluated their potential as a prognostic biomarker of cachexia-associated fat loss. This review confirms the need for further studies to identify valid prognostic biomarkers to identify loss of fat based on changes in plasma levels of biomarkers.

  3. [Cannabinoids in the treatment of the cachexia-anorexia syndrome in palliative care patients].

    Science.gov (United States)

    Nauck, F; Klaschik, E

    2004-06-01

    Loss of appetite and cachexia are frequent symptoms in palliative care patients. However, therapeutic regimens often prove ineffective, and the quality of life of many patients is significantly impaired by these symptoms. Causes and pathophysiology of anorexia and cachexia are complex and must be identified and treated. Symptomatic pharmacological therapy aims at metabolic, neuroendocrinological and catabolic changes. Prokinetic drugs, corticosteroids and gestagenes are used for symptomatic therapy. Recently, the use of cannabinoids for treatment of loss of appetite and cachexia has become the focus of interest. In cancer patients, cannabinoids proved more effective than placebo but less than gestagenes. Compared to placebo, higher efficacy of cannabinoids could be demonstrated in patients with AIDS as well as in patients with Morbus Alzheimer. However, side effects, such as dizziness, tiredness and daze led to discontinuation of the cannabinoid therapy in some patients.

  4. Potential Biomarkers of Fat Loss as a Feature of Cancer Cachexia

    Directory of Open Access Journals (Sweden)

    Maryam Ebadi

    2015-01-01

    Full Text Available Fat loss is associated with shorter survival and reduced quality of life in cancer patients. Effective intervention for fat loss in cachexia requires identification of the condition using prognostic biomarkers for early detection and prevention of further depletion. No biomarkers of fat mass alterations have been defined for application to the neoplastic state. Several inflammatory cytokines have been implicated in mediating fat loss associated with cachexia; however, plasma levels may not relate to adipose atrophy. Zinc-α2-glycoprotein may be a local catabolic mediator within adipose tissue rather than serving as a plasma biomarker of fat loss. Plasma glycerol and leptin associate with adipose tissue atrophy and mass, respectively; however, no study has evaluated their potential as a prognostic biomarker of cachexia-associated fat loss. This review confirms the need for further studies to identify valid prognostic biomarkers to identify loss of fat based on changes in plasma levels of biomarkers.

  5. Inhibition of ER stress and unfolding protein response pathways causes skeletal muscle wasting during cancer cachexia

    Science.gov (United States)

    Bohnert, Kyle R.; Gallot, Yann S.; Sato, Shuichi; Xiong, Guangyan; Hindi, Sajedah M.; Kumar, Ashok

    2016-01-01

    Cachexia is a devastating syndrome that causes morbidity and mortality in a large number of patients with cancer. However, the mechanisms of cancer cachexia remain poorly understood. Accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes stress. The ER responds to this stress through activating certain pathways commonly known as the unfolding protein response (UPR). The main function of UPR is to restore homeostasis, but excessive or prolonged activation of UPR can lead to pathologic conditions. In this study, we examined the role of ER stress and UPR in regulation of skeletal muscle mass in naïve conditions and during cancer cachexia. Our results demonstrate that multiple markers of ER stress are highly activated in skeletal muscle of Lewis lung carcinoma (LLC) and ApcMin/+ mouse models of cancer cachexia. Treatment of mice with 4-phenylbutyrate (4-PBA), a chemical chaperon and a potent inhibitor of ER stress, significantly reduced skeletal muscle strength and mass in both control and LLC-bearing mice. Blocking the UPR also increased the proportion of fast-type fibers in soleus muscle of both control and LLC-bearing mice. Inhibition of UPR reduced the activity of Akt/mTOR pathway and increased the expression of the components of the ubiquitin–proteasome system and autophagy in LLC-bearing mice. Moreover, we found that the inhibition of UPR causes severe atrophy in cultured myotubes. Our study provides initial evidence that ER stress and UPR pathways are essential for maintaining skeletal muscle mass and strength and for protection against cancer cachexia.—Bohnert, K. R., Gallot, Y. S., Sato, S., Xiong, G., Hindi, S. M., Kumar, A. Inhibition of ER stress and unfolding protein response pathways causes skeletal muscle wasting during cancer cachexia. PMID:27206451

  6. Pancreatic cancerrelated cachexia: influence on metabolism and correlation to weight loss and pulmonary function

    Directory of Open Access Journals (Sweden)

    Büchler Markus W

    2009-07-01

    Full Text Available Abstract Background Dramatic weight loss is an often underestimated symptom in pancreatic cancer patients. Cachexia- defined as an unintended loss of stable weight exceeding 10% – is present in up to 80% of patients with cancer of the upper gastrointestinal tract, and has a significant influence on survival. The aim of the study was to show the multiple systemic effects of cachexia in pancreatic cancer patients, in terms of resection rate, effects on pulmonary function, amount of fat and muscle tissue, as well as changes in laboratory parameters. Methods In patients with pancreatic cancer, clinical appearance was documented, including the amount of weight loss. Laboratory parameters and lung-function tests were evaluated, and the thickness of muscle and fat tissue was measured with computed tomography scans. Statistical analysis, including multivariate analysis, was performed using SPSS software. Survival curves were calculated using Kaplan-Meier analysis and the log-rank test. To test for significant differences between the examined groups we used Student's t-test and the Mann-Whitney U test. Significance was defined as p Results Of 198 patients with a ductal adenocarcinoma of the pancreas, 70% were suffering from weight loss when they presented for operation, and in 40% weight loss exceeded 10% of the stable weight. In patients with cachexia, metastases were diagnosed significantly more often (47% vs. 24%, P Conclusion Pancreatic cancer patients with cachexia had a higher rate of more progressed tumour stages and a worse nutritional status. Furthermore, patients with cachexia had an impaired lung function and a reduction in fat tissue. Patients with pancreatic cancer and cachexia had significantly reduced survival. If weight loss exceeded 5% there was a significantly reduced resection rate to detect, but the changes were significantly more substantial if weight loss was 10% or more. We propose that a weight loss of 10% be defined as

  7. Diet composition as a source of variation in experimental animal models of cancer cachexia

    Science.gov (United States)

    Giles, Kaitlin; Guan, Chen; Jagoe, Thomas R.

    2015-01-01

    Abstract Background A variety of experimental animal models are used extensively to study mechanisms underlying cancer cachexia, and to identify potential treatments. The important potential confounding effect of dietary composition and intake used in many preclinical studies of cancer cachexia is frequently overlooked. Dietary designs applied in experimental studies should maximize the applicability to human cancer cachexia, meeting the essential requirements of the species used in the study, matched between treatment and control groups as well as also being generally similar to human consumption. Methods A literature review of scientific studies using animal models of cancer and cancer cachexia with dietary interventions was performed. Studies that investigated interventions using lipid sources were selected as the focus of discussion. Results The search revealed a number of nutrient intervention studies (n = 44), with the majority including n‐3 fatty acids (n = 16), mainly eicosapentaenoic acid and/or docosahexaenoic acid. A review of the literature revealed that the majority of studies do not provide information about dietary design; food intake or pair‐feeding is rarely reported. Further, there is a lack of standardization in dietary design, content, source, and overall composition in animal models of cancer cachexia. A model is proposed with the intent of guiding dietary design in preclinical studies to enable comparisons of dietary treatments within the same study, translation across different study designs, as well as application to human nutrient intakes. Conclusion The potential for experimental endpoints to be affected by variations in food intake, macronutrient content, and diet composition is likely. Diet content and composition should be reported, and food intake assessed. Minimum standards for diet definition in cachexia studies would improve reproducibility of pre‐clinical studies and aid the interpretation and translation of results

  8. High prevalence of cachexia in newly diagnosed head and neck cancer patients: An exploratory study.

    Science.gov (United States)

    Jager-Wittenaar, Harriët; Dijkstra, Pieter U; Dijkstra, Gerard; Bijzet, Johan; Langendijk, Johannes A; van der Laan, Bernard F A M; Roodenburg, Jan L N

    2017-03-01

    In patients with cancer, weight loss can be related to simple starvation, disturbed metabolism, or both. In patients with head and neck cancer (HNC), weight loss often is attributed to simple starvation because the obvious oral symptoms are known to hinder dietary intake. In this population, cachexia remains a relatively unexplored phenomenon. The aim of this study was to explore the prevalence of cachexia and precachexia in patients with newly diagnosed HNC. Fifty-nine patients with newly diagnosed HNC were asked to participate in the prospective cohort study, from which only baseline data were used in the analyses. Measurements were performed 1 wk before cancer treatment, that is, cachexia status by Fearon's cancer-specific framework, dietary intake, muscle mass, muscle strength, and biochemical markers (C-reactive protein, albumin, hemoglobin, interleukin-1β, interleukin-6, and tumor necrosis factor-α) were assessed. Data of 26 patients were included in the analyses (59% participation rate). Forty-two percent of the patients (n = 12) were classified as cachectic and 15% (n = 4) as precachectic. Muscle mass depletion was significantly more frequent in cachectic patients (67%) than in noncachectic patients (14%; P = 0.014). No differences in inflammatory markers were observed between cachectic and noncachectic patients. This exploratory study suggested a high prevalence of cachexia (42%) in patients with newly diagnosed HNC. Although a large study is needed to further elucidate the role of cachexia in patients with HNC, the data presented here suggest that cachexia is a common problem in this patient population, which has therapeutic and prognostic implications. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Metalloproteinase expression is altered in cardiac and skeletal muscle in cancer cachexia.

    Science.gov (United States)

    Devine, Raymond D; Bicer, Sabahattin; Reiser, Peter J; Velten, Markus; Wold, Loren E

    2015-08-15

    Cardiac and skeletal muscle dysfunction is a recognized effect of cancer-induced cachexia, with alterations in heart function leading to heart failure and negatively impacting patient morbidity. Cachexia is a complex and multifaceted disease state with several potential contributors to cardiac and skeletal muscle dysfunction. Matrix metalloproteinases (MMPs) are a family of enzymes capable of degrading components of the extracellular matrix (ECM). Changes to the ECM cause disruption both in the connections between cells at the basement membrane and in cell-to-cell interactions. In the present study, we used a murine model of C26 adenocarcinoma-induced cancer cachexia to determine changes in MMP gene and protein expression in cardiac and skeletal muscle. We analyzed MMP-2, MMP-3, MMP-9, and MMP-14 as they have been shown to contribute to both cardiac and skeletal muscle ECM changes and, thereby, to pathology in models of heart failure and muscular dystrophy. In our model, cardiac and skeletal muscles showed a significant increase in RNA and protein levels of several MMPs and tissue inhibitors of metalloproteinases. Cardiac muscle showed significant protein increases in MMP-2, MMP-3, MMP-9, and MMP-14, whereas skeletal muscles showed increases in MMP-2, MMP-3, and MMP-14. Furthermore, collagen deposition was increased after C26 adenocarcinoma-induced cancer cachexia as indicated by an increased left ventricular picrosirius red-positive-stained area. Increases in serum hydroxyproline suggest increased collagen turnover, implicating skeletal muscle remodeling. Our findings demonstrate that cancer cachexia-associated matrix remodeling results in cardiac fibrosis and possible skeletal muscle remodeling. With these findings, MMPs represent a possible therapeutic target for the treatment of cancer-induced cachexia. Copyright © 2015 the American Physiological Society.

  10. Liver inflammation and metabolic signaling in ApcMin/+ mice: the role of cachexia progression.

    Directory of Open Access Journals (Sweden)

    Aditi A Narsale

    Full Text Available The ApcMin/+ mouse exhibits an intestinal tumor associated loss of muscle and fat that is accompanied by chronic inflammation, insulin resistance and hyperlipidemia. Since the liver governs systemic energy demands through regulation of glucose and lipid metabolism, it is likely that the liver is a pathological target of cachexia progression in the ApcMin/+ mouse. The purpose of this study was to determine if cancer and the progression of cachexia affected liver endoplasmic reticulum (ER-stress, inflammation, metabolism, and protein synthesis signaling. The effect of cancer (without cachexia was examined in wild-type and weight-stable ApcMin/+ mice. Cachexia progression was examined in weight-stable, pre-cachectic, and severely-cachectic ApcMin/+ mice. Livers were analyzed for morphology, glycogen content, ER-stress, inflammation, and metabolic changes. Cancer induced hepatic expression of ER-stress markers BiP (binding immunoglobulin protein, IRE-1α (endoplasmic reticulum to nucleus signaling 1, and inflammatory intermediate STAT-3 (signal transducer and activator of transcription 3. While gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK mRNA expression was suppressed by cancer, glycogen content or protein synthesis signaling remained unaffected. Cachexia progression depleted liver glycogen content and increased mRNA expression of glycolytic enzyme PFK (phosphofrucktokinase and gluconeogenic enzyme PEPCK. Cachexia progression further increased pSTAT-3 but suppressed p-65 and JNK (c-Jun NH2-terminal kinase activation. Interestingly, progression of cachexia suppressed upstream ER-stress markers BiP and IRE-1α, while inducing its downstream target CHOP (DNA-damage inducible transcript 3. Cachectic mice exhibited a dysregulation of protein synthesis signaling, with an induction of p-mTOR (mechanistic target of rapamycin, despite a suppression of Akt (thymoma viral proto-oncogene 1 and S6 (ribosomal protein S6 phosphorylation. Thus

  11. Liver Inflammation and Metabolic Signaling in ApcMin/+ Mice: The Role of Cachexia Progression

    Science.gov (United States)

    Narsale, Aditi A.; Enos, Reilly T.; Puppa, Melissa J.; Chatterjee, Saurabh; Murphy, E. Angela; Fayad, Raja; Pena, Majorette O’; Durstine, J. Larry; Carson, James A.

    2015-01-01

    The ApcMin/+ mouse exhibits an intestinal tumor associated loss of muscle and fat that is accompanied by chronic inflammation, insulin resistance and hyperlipidemia. Since the liver governs systemic energy demands through regulation of glucose and lipid metabolism, it is likely that the liver is a pathological target of cachexia progression in the ApcMin/+ mouse. The purpose of this study was to determine if cancer and the progression of cachexia affected liver endoplasmic reticulum (ER)-stress, inflammation, metabolism, and protein synthesis signaling. The effect of cancer (without cachexia) was examined in wild-type and weight-stable ApcMin/+ mice. Cachexia progression was examined in weight-stable, pre-cachectic, and severely-cachectic ApcMin/+ mice. Livers were analyzed for morphology, glycogen content, ER-stress, inflammation, and metabolic changes. Cancer induced hepatic expression of ER-stress markers BiP (binding immunoglobulin protein), IRE-1α (endoplasmic reticulum to nucleus signaling 1), and inflammatory intermediate STAT-3 (signal transducer and activator of transcription 3). While gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was suppressed by cancer, glycogen content or protein synthesis signaling remained unaffected. Cachexia progression depleted liver glycogen content and increased mRNA expression of glycolytic enzyme PFK (phosphofrucktokinase) and gluconeogenic enzyme PEPCK. Cachexia progression further increased pSTAT-3 but suppressed p-65 and JNK (c-Jun NH2-terminal kinase) activation. Interestingly, progression of cachexia suppressed upstream ER-stress markers BiP and IRE-1α, while inducing its downstream target CHOP (DNA-damage inducible transcript 3). Cachectic mice exhibited a dysregulation of protein synthesis signaling, with an induction of p-mTOR (mechanistic target of rapamycin), despite a suppression of Akt (thymoma viral proto-oncogene 1) and S6 (ribosomal protein S6) phosphorylation. Thus, cancer

  12. Metabolomics Evaluation of Serum Markers for Cachexia and Their Intra-Day Variation in Patients with Advanced Pancreatic Cancer

    Science.gov (United States)

    Fujiwara, Yutaka; Kobayashi, Takashi; Chayahara, Naoko; Imamura, Yoshinori; Toyoda, Masanori; Kiyota, Naomi; Mukohara, Toru; Nishiumi, Shin; Azuma, Takeshi; Yoshida, Masaru; Minami, Hironobu

    2014-01-01

    Purpose Cancer cachexia is a multifactorial syndrome characterized by progressive loss of weight and muscle atrophy. Using metabolomics, we investigated serum markers and their intra-day variation in advanced pancreatic cancer patients with cachexia. Methods Patients were enrolled in two groups: those with or without cachexia. Blood samples collected at 6:30 AM, 11:30 AM, 4:30 PM, and 9:30 PM were analyzed using metabolomics, and serum levels of IL-6, TNF-α, and leptin were measured and compared between the two groups. Intra-day variation was then evaluated. Results Twenty-one patients were enrolled in total. In the cachexia group (n = 9), median body weight loss rate over 6 months was greater, performance status was poorer, and anorexia was more severe than in the non-cachexia group (n = 12). Each metabolites level showed substantial intra-day variation, and some of them displayed significant differences between the two groups. Levels of paraxanthine remained markedly lower in the cohort with cachexia at all measurement points. Besides, median IL-6 and TNF-α levels appeared higher and leptin concentration appeared lower in the cachexia group, albeit without statistical significance. Conclusion Some metabolites and some serological marker levels were affected by cancer cachexia. Although paraxanthine levels were consistently lower in patients with cachexia, we identified that many metabolites indicated large intra- and inter-day variation and that it might be necessary to pay attention to intra-day variation in metabolomics research. PMID:25411961

  13. Cancer cachexia causes skeletal muscle damage via transient receptor potential vanilloid 2-independent mechanisms, unlike muscular dystrophy.

    Science.gov (United States)

    Iwata, Yuko; Suzuki, Nobuyuki; Ohtake, Hitomi; Kamauchi, Shinya; Hashimoto, Naohiro; Kiyono, Tohru; Wakabayashi, Shigeo

    2016-06-01

    Muscle wasting during cancer cachexia contributes to patient morbidity. Cachexia-induced muscle damage may be understood by comparing its symptoms with those of other skeletal muscle diseases, but currently available data are limited. We modelled cancer cachexia in mice bearing Lewis lung carcinoma/colon adenocarcinoma and compared the associated muscle damage with that in a murine muscular dystrophy model (mdx mice). We measured biochemical and immunochemical parameters: amounts/localization of cytoskeletal proteins and/or Ca(2+) signalling proteins related to muscle function and abnormality. We analysed intracellular Ca(2+) mobilization and compared results between the two models. Involvement of Ca(2+)-permeable channel transient receptor potential vanilloid 2 (TRPV2) was examined by inoculating Lewis lung carcinoma cells into transgenic mice expressing dominant-negative TRPV2. Tumourigenesis caused loss of body and skeletal muscle weight and reduced muscle force and locomotor activity. Similar to mdx mice, cachexia muscles exhibited myolysis, reduced sarcolemmal sialic acid content, and enhanced lysosomal exocytosis and sarcolemmal localization of phosphorylated Ca(2+)/CaMKII. Abnormal autophagy and degradation of dystrophin also occurred. Unlike mdx muscles, cachexia muscles did not exhibit regeneration markers (centrally nucleated fibres), and levels of autophagic proteolytic pathway markers increased. While a slight accumulation of TRPV2 was observed in cachexia muscles, Ca(2+) influx via TRPV2 was not elevated in cachexia-associated myotubes, and the course of cachexia pathology was not ameliorated by dominant-negative inhibition of TRPV2. Thus, cancer cachexia may induce muscle damage through TRPV2-independent mechanisms distinct from those in muscular dystrophy; this may help treat patients with tumour-induced muscle wasting.

  14. Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and Japan: facts and numbers update 2016.

    Science.gov (United States)

    von Haehling, Stephan; Anker, Markus S; Anker, Stefan D

    2016-12-01

    Cachexia is a serious clinical consequence of almost all chronic diseases when reaching advanced stages. Its prevalence ranges from 5-15% in end-stage chronic heart failure to 50-80% in advanced malignant cancer. Cachexia is also frequently occurring in patients with chronic kidney disease, chronic obstructive pulmonary disease (COPD) or neurological diseases, and rheumatoid arthritis. Mortality rates of patients with cachexia range from 15-25% per year in severe COPD through 20-40% per year in patients with chronic heart failure or chronic kidney disease to 20-80% in cancer cachexia. In the industrialized world (North America, Europe, and Japan) where epidemiological data are to some degree available, the overall prevalence of cachexia (due to any disease and not necessarily associated with hospital admission) is growing with the growth of the chronic illness prevalence, and it currently affects around 0.5-1.0% of the population, i.e. around 6-12 million people. From this, one can estimate that 1.5-2 million deaths are occurring in patients with cachexia per year. It is also a very significant health problem in other parts of the globe, but epidemiological data are scarce. The multifactorial nature of cachexia is now much better understood, and particularly, the role of inflammatory mediators and the imbalance of anabolism and catabolism are considered important therapeutic targets. Several approaches to develop cachexia and muscle wasting treatments have failed to be successful in phase III clinical trials, but new approaches are in development. Given the high prevalence and very high mortality associated with cachexia, advances are urgently needed for patients worldwide.

  15. Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in colon-26 tumor.

    Science.gov (United States)

    Strassmann, G; Masui, Y; Chizzonite, R; Fong, M

    1993-03-15

    In the colon-26 (C-26) tumor model, the cytokine IL-6 is an important factor involved in experimental cancer cachexia. Recent in vitro data indicated that IL-1 plays a role in the interaction between host macrophages and C-26 cells that express IL-1R, resulting in the amplification of tumor IL-6 production. To investigate the role of IL-1 on the development of C-26 cachexia in vivo, the effect of specific blockade of the action of IL-1 with reagents against IL-1R was evaluated. Both IL-1R antagonist (IL-1RA) and the mAb 35F5 directed against IL-1R type I, prevented binding of radioactive IL-1, and inhibited IL-1-induced IL-6 synthesis by the C-26 cell line. Whereas a systemic administration of these reagents did not reverse weight loss in C-26-bearing mice, intratumoral injections of IL-1RA significantly reduced cachexia. Furthermore, body composition analysis confirmed that this treatment improved lean tissue and fat, as well as hypoglycemia and serum IL-6 level. The fact that the treatment did not change the tumor burden suggests that it affected the host directly. These results support the hypothesis that, at the microenvironment of the C-26 tumor, IL-1 is involved in the cachexia endured by the host.

  16. Systemic inflammation in chronic obstructive pulmonary disease and lung cancer: common driver of pulmonary cachexia?

    Science.gov (United States)

    Ceelen, Judith J M; Langen, Ramon C J; Schols, Annemie M W J

    2014-12-01

    In this article, a putative role of systemic inflammation as a driver of pulmonary cachexia induced by either chronic obstructive pulmonary disease or nonsmall cell lung cancer is reviewed. Gaps in current translational research approaches are discussed and alternative strategies are proposed to provide new insights. Activation of the ubiquitin proteasome system has generally been considered a cause of pulmonary cachexia, but current animal models lack specificity and evidence is lacking in nonsmall cell lung cancer and conflicting in chronic obstructive pulmonary disease patients. Recent studies have shown activation of the autophagy-lysosome pathway in both nonsmall cell lung cancer and chronic obstructive pulmonary disease. Myonuclear loss, as a consequence of increased apoptotic events in myofibers, has been suggested in cancer-cachexia-associated muscle atrophy. Plasma transfer on myotube cultures can be used to detect early inflammatory signals in patients and presence of atrophy-inducing activity within the circulation. Comparative clinical research between nonsmall cell lung cancer and chronic obstructive pulmonary disease in different disease stages is useful to unravel disease-specific versus common denominators of pulmonary cachexia.

  17. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting1234

    Science.gov (United States)

    Gullett, Norleena P; Hebbar, Gautam

    2010-01-01

    This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, megestrol acetate) in malnutrition and other catabolic states has been the subject of considerable research during the past several decades. Research on the effects of these agents in cachexia or wasting conditions, characterized by progressive loss of skeletal muscle and adipose tissue, focused on patients with AIDS in the early 1990s, when the devastating effects of the loss of body weight, lean body mass, and adipose tissue were recognized as contributors to these patients' mortality. These same agents have also been studied as methods to attenuate the catabolic responses observed in cancer-induced cachexia and in wasting induced by chronic obstructive pulmonary disease, congestive heart failure, renal failure, and other conditions. This article provides an updated review of recent clinical trials that specifically examined the potential therapeutic roles of growth hormone, testosterone, oxandrolone, and megestrol acetate and emerging data on the orexigenic peptide ghrelin, in human cachexia and wasting. PMID:20164318

  18. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting.

    Science.gov (United States)

    Gullett, Norleena P; Hebbar, Gautam; Ziegler, Thomas R

    2010-04-01

    This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, megestrol acetate) in malnutrition and other catabolic states has been the subject of considerable research during the past several decades. Research on the effects of these agents in cachexia or wasting conditions, characterized by progressive loss of skeletal muscle and adipose tissue, focused on patients with AIDS in the early 1990s, when the devastating effects of the loss of body weight, lean body mass, and adipose tissue were recognized as contributors to these patients' mortality. These same agents have also been studied as methods to attenuate the catabolic responses observed in cancer-induced cachexia and in wasting induced by chronic obstructive pulmonary disease, congestive heart failure, renal failure, and other conditions. This article provides an updated review of recent clinical trials that specifically examined the potential therapeutic roles of growth hormone, testosterone, oxandrolone, and megestrol acetate and emerging data on the orexigenic peptide ghrelin, in human cachexia and wasting.

  19. The central role of hypothalamic inflammation in the acute illness response and cachexia.

    Science.gov (United States)

    Burfeind, Kevin G; Michaelis, Katherine A; Marks, Daniel L

    2016-06-01

    When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Cancer-induced cardiac cachexia: Pathogenesis and impact of physical activity (Review).

    Science.gov (United States)

    Belloum, Yassine; Rannou-Bekono, Françoise; Favier, François B

    2017-05-01

    Cachexia is a wasting syndrome observed in many patients suffering from several chronic diseases including cancer. In addition to the progressive loss of skeletal muscle mass, cancer cachexia results in cardiac function impairment. During the severe stage of the disease, patients as well as animals bearing cancer cells display cardiac atrophy. Cardiac energy metabolism is also impeded with disruption of mitochondrial homeostasis and reduced oxidative capacity, although the available data remain equivocal. The release of inflammatory cytokines by tumor is a key mechanism in the initiation of heart failure. Oxidative stress, which results from the combination of chemotherapy, inadequate antioxidant consumption and chronic inflammation, will further foster heart failure. Protein catabolism is due to the concomitant activation of proteolytic systems and inhibition of protein synthesis, both processes being triggered by the deactivation of the Akt/mammalian target of rapamycin pathway. The reduction in oxidative capacity involves AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1α dysregulation. The nuclear factor-κB transcription factor plays a prominent role in the coordination of these alterations. Physical exercise appears as an interesting non-pharmaceutical way to counteract cancer cachexia-induced-heart failure. Indeed, aerobic training has anti-inflammatory effects, increases anti-oxidant defenses, prevents atrophy and promotes oxidative metabolism. The present review points out the importance of better understanding the concurrent structural and metabolic changes within the myocardium during cancer and the protective effects of exercise against cardiac cachexia.

  1. Functional body composition and related aspects in research on obesity and cachexia

    DEFF Research Database (Denmark)

    Müller, M J; Baracos, V; Bosy-Westphal, A

    2014-01-01

    The 12th Stock Conference addressed body composition and related functions in two extreme situations, obesity and cancer cachexia. The concept of 'functional body composition' integrates body components into regulatory systems relating the mass of organs and tissues to corresponding in vivo funct...

  2. AKT1 and SELP Polymorphisms Predict the Risk of Developing Cachexia in Pancreatic Cancer Patients

    Science.gov (United States)

    Le Large, Tessa Y. S.; Mambrini, Andrea; Funel, Niccola; Maftouh, Mina; Ghayour-Mobarhan, Majid; Cantore, Maurizio; Boggi, Ugo; Peters, Godefridus J.

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) patients have the highest risk of developing cachexia, which is a direct cause of reduced quality of life and shorter survival. Novel biomarkers to identify patients at risk of cachexia are needed and might have a substantial impact on clinical management. Here we investigated the prognostic value and association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia in PDAC. Genotyping was performed in DNA from blood samples of a test and validation cohorts of 151 and 152 chemo-naive locally-advanced/metastatic PDAC patients, respectively. The association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia as well as the correlation between cachexia and the candidate polymorphisms and overall survival were analyzed. Akt expression and phosphorylation in muscle biopsies were evaluated by specific ELISA assays. SELP-rs6136-AA and AKT1-rs1130233-AA/GA genotypes were associated with increased risk of developing cachexia in both cohorts (SELP: p = 0.011 and p = 0.045; AKT1: p = 0.004 and p = 0.019 for the first and second cohorts, respectively), while patients carrying AKT1-rs1130233-GG survived significantly longer (p = 0.002 and p = 0.004 for the first and second cohorts, respectively). In the multivariate analysis AKT1-rs1130233-AA/GA genotypes were significant predictors for shorter survival, with an increased risk of death of 1.7 (p = 0.002) and 1.6 (p = 0.004), in the first and second cohorts, respectively. This might be explained by the reduced phosphorylation of Akt1 in muscle biopsies from patients harboring AKT1-rs1130233-AA/GA (p = 0.003), favoring apoptosis induction. In conclusion, SELP and AKT1 polymorphisms may play a role in the risk of cachexia and death in PDAC patients, and should be further evaluated in larger prospective studies. PMID:25238546

  3. Unsatisfactory knowledge and use of terminology regarding malnutrition, starvation, cachexia and sarcopenia among dietitians.

    Science.gov (United States)

    Ter Beek, Lies; Vanhauwaert, Erika; Slinde, Frode; Orrevall, Ylva; Henriksen, Christine; Johansson, Madelene; Vereecken, Carine; Rothenberg, Elisabet; Jager-Wittenaar, Harriët

    2016-12-01

    Clinical signs of malnutrition, starvation, cachexia and sarcopenia overlap, as they all imply muscle wasting to a various extent. However, the underlying mechanisms differ fundamentally and therefore distinction between these phenomena has therapeutic and prognostic implications. We aimed to determine whether dietitians in selected European countries have 'sufficient knowledge' regarding malnutrition, starvation, cachexia and sarcopenia, and use these terms in their daily clinical work. An anonymous online survey was performed among dietitians in Belgium, the Netherlands, Norway and Sweden. 'Sufficient knowledge' was defined as having mentioned at least two of the three common domains of malnutrition according to ESPEN definition of malnutrition (2011): 'nutritional balance', 'body composition' and 'functionality and clinical outcome', and a correct answer to three cases on starvation, cachexia and sarcopenia. Chi-square test was used to analyse differences in experience, work place and number of malnourished patients treated between dietitians with 'sufficient knowledge' vs. 'less sufficient knowledge'. 712/7186 responded to the questionnaire, of which data of 369 dietitians were included in the analysis (5%). The term 'malnutrition' is being used in clinical practice by 88% of the respondents. Starvation, cachexia and sarcopenia is being used by 3%, 30% and 12% respectively. The cases on starvation, cachexia and sarcopenia were correctly identified by 58%, 43% and 74% respectively. 13% of the respondents had 'sufficient knowledge'. 31% of the respondents identified all cases correctly. The proportion of respondents with 'sufficient knowledge' was significantly higher in those working in a hospital or in municipality (16%, P cachexia and sarcopenia is unsatisfactory (13%). The terms starvation, cachexia and sarcopenia are not often used by dietitians in daily clinical work. As only one-third (31%) of dietitians identified all cases correctly, the results of this

  4. An analysis of the types of recently published research in the field of cachexia.

    Science.gov (United States)

    Shewan, Louise G

    2017-11-01

    Introduction Cachexia is a common complication of many and varied chronic disease processes, yet it has received very little attention as an area of clinical research effort until recently. We sought to survey the contemporary literature on published research into cachexia to define where it is being published and the proportion of output classified into the main types of research output. Methods I searched the PubMed listings under the topic research term "cachexia" and related terms for articles published in the calendar years of 2015 and 2016, regardless of language. Searches were conducted and relevant papers extracted by two observers, and disagreements were resolved by consensus. Results There were 954 publications, 370 of which were review articles or commentaries, 254 clinical observations or non-randomised trials, 246 original basic science reports and only 26 were randomised controlled trials. These articles were published in 478 separate journals but with 36% of them being published in a core set of 23 journals. The H-index of these papers was 25 and there were 147 papers with 10 or more citations. Of the top 100 cited papers, 25% were published in five journals. Of the top cited papers, 48% were review articles, 18% were original basic science, and 7% were randomised clinical trials. Discussion This analysis shows a steady but modest increase in publications concerning cachexia with a strong pipeline of basic science research but still a relative lack of randomised clinical trials, with none exceeding 1000 patients. Research in cachexia is still in its infancy, but the solid basic science effort offers hope that translation into randomised controlled clinical trials may eventually lead to effective therapies for this troubling and complex clinical disease process.

  5. Potentiation of ghrelin signaling attenuates cancer anorexia–cachexia and prolongs survival

    Science.gov (United States)

    Fujitsuka, N; Asakawa, A; Uezono, Y; Minami, K; Yamaguchi, T; Niijima, A; Yada, T; Maejima, Y; Sedbazar, U; Sakai, T; Hattori, T; Kase, Y; Inui, A

    2011-01-01

    Cancer anorexia–cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut–brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia–cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia–cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia–cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia–cachexia. PMID:22832525

  6. Use of ghrelin in cachexia syndrome: a systematic review of clinical trials.

    Science.gov (United States)

    Mansson, Jéssica V; Alves, Fernanda D; Biolo, Andréia; Souza, Gabriela C

    2016-11-01

    Ghrelin is a hormone that stimulates weight gain and increases appetite. For these reasons, it has been used for treatment of cachexia syndrome. The aim of this systematic review was to examine the use of ghrelin in cachexia patients to better understand the most prevalent clinical outcomes, particularly since the type and dosage of hormone used and the route and duration of administration often varies. A search of electronic databases (MEDLINE, SciELO, Embase, Cochrane Library, and Clinical Trials.gov) was limited to original articles describing interventions in adult humans, with no limits for publication date or language. Articles were searched independently by 2 reviewers, from October 2013 to April 2015. Studies were eligible for inclusion if they were conducted in adult patients with a diagnosis of cachexia and provided information on type of ghrelin or analogue used, route of administration and dose administered, duration of intervention, outcomes, and clinical trial study design. Data were extracted independently by 2 reviewers using a preconstructed spreadsheet. Initially, 573 references were identified. Seven articles describing 379 participants were selected for review. Ghrelin was found to have a predominantly positive effect on growth hormone plasma levels, weight gain, increases in lean mass, and reductions in loss of adipose tissue. Although the studies reviewed here report positive results, there is still little evidence available on the use of ghrelin to treat cachexia. Further research is required to determine conclusively whether the use of ghrelin in patients with cachexia is a viable therapy. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Continuous Release of Tumor-Derived Factors Improves the Modeling of Cachexia in Muscle Cell Culture

    Directory of Open Access Journals (Sweden)

    Robert W. Jackman

    2017-09-01

    Full Text Available Cachexia is strongly associated with a poor prognosis in cancer patients but the biological trigger is unknown and therefore no therapeutics exist. The loss of skeletal muscle is the most deleterious aspect of cachexia and it appears to depend on secretions from tumor cells. Models for studying wasting in cell culture consist of experiments where skeletal muscle cells are incubated with medium conditioned by tumor cells. This has led to candidates for cachectic factors but some of the features of cachexia in vivo are not yet well-modeled in cell culture experiments. Mouse myotube atrophy measured by myotube diameter in response to medium conditioned by mouse colon carcinoma cells (C26 is consistently less than what is seen in muscles of mice bearing C26 tumors with moderate to severe cachexia. One possible reason for this discrepancy is that in vivo the C26 tumor and skeletal muscle share a circulatory system exposing the muscle to tumor factors in a constant and increasing way. We have applied Transwell®-adapted cell culture conditions to more closely simulate conditions found in vivo where muscle is exposed to the ongoing kinetics of constant tumor secretion of active factors. C26 cells were incubated on a microporous membrane (a Transwell® insert that constitutes the upper compartment of wells containing plated myotubes. In this model, myotubes are exposed to a constant supply of cancer cell secretions in the medium but without direct contact with the cancer cells, analogous to a shared circulation of muscle and cancer cells in tumor-bearing animals. The results for myotube diameter support the idea that the use of Transwell® inserts serves as a more physiological model of the muscle wasting associated with cancer cachexia than the bolus addition of cancer cell conditioned medium. The Transwell® model supports the notion that the dose and kinetics of cachectic factor delivery to muscle play a significant role in the extent of pathology.

  8. Mechanisms of Anorexia Cancer Cachexia Syndrome and Potential Benefits of Traditional Medicine and Natural Herbs.

    Science.gov (United States)

    Ming-Hua, Cong; Bao-Hua, Zou; Lei, Yu

    Anorexia cancer cachexia syndrome is prevalent in advanced cancer patients, which is featured by anorexia, decreased dietary intake, body weight loss (skeletal muscle mass loss), and is unable to be reversed by routine nutritional support therapy. Up to now, the main mechanisms involved in cancer cachexia include excessive systemic inflammation, which is represented by increased plasma levels of IL-1, IL-6, TNF-alpha, tumor-induced factors, such as PIF and LMF. These factors eventually act on orexigenic and anorexigenicneurons located in the hypothalamus or protein and lipid metabolism of peripheral tissues, which lead to anorexia, decreased dietary intake, enhanced basic metabolism rate and hypercatabolism. The treatment modality includes early nutritional intervention, physical activity and drug treatment. However, studies about drugs used to treat cachexia are always controversial or merely effective in stimulating appetite and increasing body weight, though not lean body mass. The main target of pharmaceutical treatment is to improve appetite, decrease systemic inflammation and promote anabolic metabolism. Nevertheless, the treatment effectiveness of chemical drugs are not reaching consensus by existing cachexia guidelines. Complementary and alternative medicine (CAM) is recently known as a promising treatment to improve cachaxia status and quality of life of cancer patients. Traditional Chinese medicine (TCM) and natural herbal medicines have been used in the treatment of cancer for thousands of years worldwide, particularly in China. More and more research show that traditional Hanfang (Chinese medicines) and some natural herbs with less side reactions, have the effects of antagonizing pro-inflammatory cytokines, enhancing immune system, inhibiting protein catabolism, boosting the appetite and body weight, which maybe a promising treatment strategy and development tendency for anorexia cancer cachexia syndrome.

  9. A comparison of research into cachexia, wasting and related skeletal muscle syndromes in three chronic disease areas.

    Science.gov (United States)

    Stewart Coats, Andrew J; Shewan, Louise G

    2017-05-15

    We compared the frequency of cancer, heart and lung related cachexia and cachexia-related research articles in the specialist journal, Journal of Cachexia, Sarcopenia and Muscle (JCSM) to those seen in a leading European journal in each specialist area during 2015 and 2016 to assess whether work on cachexia and related fields is relatively over or under represented in each specialist area. In the dedicated journal, Journal of Cachexia, Sarcopenia and Muscle, there were 44 references related to cancer, 5 related to respiratory disease, 5 related to heart failure, and 21 related to more than one of these chronic diseases. Despite this cancer preponderance, in the European Journal of Cancer in the two publication years, there were only 5 relevant publications (0.67% of the journal output), compared to 16 (1.41%) in the European Respiratory Journal and 10 (2.19%) in the European Journal of Heart Failure. There is considerable under-representation of cancer cachexia-related papers in the major European Cancer journal despite a high proportion in the dedicated cachexia journal. The under-representation is even more marked when expressed as a percentage, 0.67%, compared to 1.41% and 2.19% of the lung and heart journals respectively. These results are consistent with a worrying lack of interest in, or publication of, cachexia and related syndromes research in the cancer literature in Europe compared to its importance as a clinical syndrome. Greater interest is shown in lung and cardiology journals. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  10. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials.

    Science.gov (United States)

    Temel, Jennifer S; Abernethy, Amy P; Currow, David C; Friend, John; Duus, Elizabeth M; Yan, Ying; Fearon, Kenneth C

    2016-04-01

    Patients with advanced cancer frequently experience anorexia and cachexia, which are associated with reduced food intake, altered body composition, and decreased functionality. We assessed anamorelin, a novel ghrelin-receptor agonist, on cachexia in patients with advanced non-small-cell lung cancer and cachexia. ROMANA 1 and ROMANA 2 were randomised, double-blind, placebo-controlled phase 3 trials done at 93 sites in 19 countries. Patients with inoperable stage III or IV non-small-cell lung cancer and cachexia (defined as ≥5% weight loss within 6 months or body-mass index cachexia, anamorelin might be a treatment option for patients with cancer anorexia and cachexia. Helsinn Therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. The Challenge of Appropriate Identification and Treatment of Starvation, Sarcopenia, and Cachexia: A Survey of Australian Dietitians

    Directory of Open Access Journals (Sweden)

    Alison Yaxley

    2011-01-01

    Full Text Available Malnutrition is an umbrella term that includes starvation, sarcopenia, and cachexia; however, differentiating between these terms is infrequent in clinical practice. Given that the effectiveness of treatment depends on the aetiology of unintentional weight loss, it is important that clinicians are aware of the defining characteristics. The aim of this study was to determine whether Australian dietitians understand and use the terms starvation, sarcopenia, and cachexia and provide targeted treatment strategies accordingly. Members of the Dietitians Association of Australia were surveyed to gain information on practices and attitudes to diagnosis and treatment of adult malnutrition. In addition, three case studies were provided to examine understanding of starvation, sarcopenia, and cachexia. 221 dietitians accessed the survey. 81 respondents (43% indicated the use of at least one alternate term (starvation, sarcopenia, and/or cachexia. Muscle wasting was the most commonly used diagnostic criterion. High-energy high-protein diet was the most common therapy prescribed. Correct diagnoses for case studies were recorded by 6% of respondents for starvation, 46% for sarcopenia, and 21% for cachexia. There is a need for increased awareness of the existence of starvation, sarcopenia, and cachexia amongst Australian dietitians and research into appropriate methods of identification and treatment for each condition.

  12. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

    Directory of Open Access Journals (Sweden)

    Stephanie H Greco

    Full Text Available Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.

  13. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

    Science.gov (United States)

    Greco, Stephanie H; Tomkötter, Lena; Vahle, Anne-Kristin; Rokosh, Rae; Avanzi, Antonina; Mahmood, Syed Kashif; Deutsch, Michael; Alothman, Sara; Alqunaibit, Dalia; Ochi, Atsuo; Zambirinis, Constantinos; Mohaimin, Tasnima; Rendon, Mauricio; Levie, Elliot; Pansari, Mridul; Torres-Hernandez, Alejandro; Daley, Donnele; Barilla, Rocky; Pachter, H Leon; Tippens, Daniel; Malik, Hassan; Boutajangout, Allal; Wisniewski, Thomas; Miller, George

    2015-01-01

    Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.

  14. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia

    Science.gov (United States)

    Rokosh, Rae; Avanzi, Antonina; Mahmood, Syed Kashif; Deutsch, Michael; Alothman, Sara; Alqunaibit, Dalia; Ochi, Atsuo; Zambirinis, Constantinos; Mohaimin, Tasnima; Rendon, Mauricio; Levie, Elliot; Pansari, Mridul; Torres-Hernandez, Alejandro; Daley, Donnele; Barilla, Rocky; Pachter, H. Leon; Tippens, Daniel; Malik, Hassan; Boutajangout, Allal; Wisniewski, Thomas; Miller, George

    2015-01-01

    Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival. PMID:26172047

  15. Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin-6 dependent.

    Science.gov (United States)

    Reddel, C J; Allen, J D; Ehteda, A; Taylor, R; Chen, V M Y; Curnow, J L; Kritharides, L; Robertson, G

    2017-03-01

    Essentials Cancer cachexia and cancer-associated thrombosis have not previously been mechanistically linked. We assessed thrombin generation and coagulation parameters in cachectic C26 tumor-bearing mice. C26 mice are hypercoagulable, partially corrected by blocking tumor derived interleukin-6. Coagulability and anti-inflammatory interventions may be clinically important in cancer cachexia. Background Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer, which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. Objectives To assess if cancer cachexia altered the coagulation state and if this was attributable to tumor IL-6 production. Methods In male BALB/c*DBA2 (F1 hybrid) mice with a C26 tumor we used modified calibrated automated thrombogram and fibrin generation (based on overall hemostatic potential) assays to assess the functional coagulation state, and also examined fibrinogen, erythrocyte sedimentation rate (ESR), platelet count, tissue factor pathway inhibitor (TFPI) and hepatic expression of coagulation factors by microarray. C26 mice were compared with non-cachectic NC26, pair-fed and sham control mice. IL-6 expression in C26 cells was knocked down by lentiviral shRNA constructs. Results C26 mice with significant weight loss and highly elevated IL-6 had elevated thrombin generation, fibrinogen, ESR, platelets and TFPI compared with all control groups. Fibrin generation was elevated compared with pair-fed and sham controls but not compared with NC26 tumor mice. Hepatic expression of coagulation factors and fibrinolytic inhibitors was increased. Silencing IL-6 in the tumor significantly, but incompletely, attenuated the increased thrombin generation, fibrinogen and TFPI. Conclusions Cachectic C26 tumor-bearing mice are in a

  16. New experiences on the time required for the appearance of fluoric cachexia in the guinea pig following ingestion of various fluorine salts

    Energy Technology Data Exchange (ETDEWEB)

    Cristiani, H.; Chausse, P.

    1926-01-01

    Experiments were performed to compare the time it took guinea pigs to develop cachexia after being given sodium fluosilicate or sodium fluoride. Results indicate that a dose-response relationship existed following the ingestion of the fluorine salts in relation to the time it took to produce cachexia. In addition, sodium fluosilicate was found to be more toxic than sodium fluoride. In guinea pigs which were given approximately 1/30 to 1/36 of the lethal dose, cachexia was produced from 44 to 70 days later. In guinea pigs given even smaller doses, cachexia did not appear for one to two years.

  17. Publication trends in cachexia and sarcopenia in elderly heart failure patients.

    Science.gov (United States)

    Springer, Jochen; Anker, Stefan D

    2016-12-01

    The loss of skeletal mass - sarcopenia and cachexia - is considered to be a major contributor to morbidity and mortality in chronic heart failure (CHF). Unfortunately, sarcopenia is generally considered to be a geriatric syndrome, but not necessarily seen as a comorbidity in CHF, even though it has a wide range of adverse health outcomes. While there were 15,574 publication with the title word "heart failure" in PubMed in the 5‑year period from 1 June 2011 to 31 May 2016, only 22 or 71 publications were found with the search combination "sarcopenia" or "cachexia" (title word) and "heart failure" (all fields), respectively. This shows very clearly that loss of muscle quality and function due to heart failure is still an underappreciated problem in the medical field.

  18. Cachexia secondary to intracranial anaplastic (malignant) ependymoma in a boxer dog.

    Science.gov (United States)

    Borrelli, A; Mattiazzi, L; Capucchio, M T; Biolatti, C; Cagnasso, A; Gianella, P; D'Angelo, A

    2009-10-01

    An eight-year-old female boxer was referred because of weight loss of several months' duration. On physical examination, cachexia was the only reported abnormality. Neurological symptoms were shown only in the last days preceding death and consisted of altered mental status, compulsive behaviour and left rear proprioception deficit. At post-mortem examination, a voluminous, soft, haemorrhagic mass was found invading the floor of the brain. Based on the morphological features of the tumour, marked parenchymal invasion, extensive necrosis and cellular atypia, the mass was classified as an anaplastic ependymoma. This case report shows similarities to the diencephalic syndrome reported in human paediatric medicine in which the main clinical sign is a profound emaciation in spite of normal or slightly diminished caloric intake. Weight loss and cachexia are clinically relevant problems in small animals and these clinical signs should raise a suspicion, among the other differentials, of a brain tumour, even in absence of neurologic signs.

  19. Theophylline is able to partially revert cachexia in tumour-bearing rats

    Directory of Open Access Journals (Sweden)

    Olivan Mireia

    2012-08-01

    Full Text Available Abstract Background and aims The aim of the present investigation was to examine the anti-wasting effects of theophylline (a methylxantine present in tea leaves on a rat model of cancer cachexia. Methods The in vitro effects of the nutraceuticals on proteolysis were examined on muscle cell cultures submitted to hyperthermia. Individual muscle weights, muscle gene expression, body composition and cardiac function were measured in rats bearing the Yoshida AH-130 ascites hepatoma, following theophylline treatment. Results Theophylline treatment inhibited proteolysis in C2C12 cell line and resulted in an anti-proteolytic effect on muscle tissue (soleus and heart, which was associated with a decrease in circulating TNF-alpha levels and with a decreased proteolytic systems gene expression. Treatment with the nutraceutical also resulted in an improvement in body composition and cardiac function. Conclusion Theophylline - alone or in combination with drugs - may be a candidate molecule for the treatment of cancer cachexia.

  20. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting1234

    OpenAIRE

    Gullett, Norleena P; Hebbar, Gautam; Ziegler, Thomas R

    2010-01-01

    This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, m...

  1. Tumor-Secreted Autocrine Motility Factor (AMF): Casual Role in a Animal Model of Cachexia

    Science.gov (United States)

    2004-08-01

    clinical features: 1) loss of appetite (anorexia), 2) nutritional mal-absorption, and 3) muscle and fat wasting caused by tumor-stimulated factors...with interferon-gamma-producing tumor cells. Int J Cancer 49:77-82 Matthys P, Billiau A (1997). Cytokines and cachexia. Nutrition 13:763-770 McDevitt H...resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia . J Mol Biol 309:447-463 Reinheckel T, Grune T, Davies KJ

  2. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer.

    Directory of Open Access Journals (Sweden)

    Stefanie Aust

    Full Text Available Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC. Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs ascertained by pre-operative computed tomography (CT. Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients.We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient's outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis.Muscle attenuation (MA-a well established BCM parameter-is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028. Low MA-reflecting a state of cachexia-is also associated with residual tumor after cytoreductive surgery (p = 0.046 and with an unfavorable performance status (p = 0.015. Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively.MA-ascertained by routine pre-operative CT-is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA.

  3. Development of the EORTC QLQ-CAX24, A Questionnaire for Cancer Patients With Cachexia.

    Science.gov (United States)

    Wheelwright, Sally J; Hopkinson, Jane B; Darlington, Anne-Sophie; Fitzsimmons, Deborah F; Fayers, Peter; Balstad, Trude R; Bredart, Anne; Hammerlid, Eva; Kaasa, Stein; Nicolatou-Galitis, Ourania; Pinto, Monica; Schmidt, Heike; Solheim, Tora S; Strasser, Florian; Tomaszewska, Iwona M; Johnson, Colin D

    2017-02-01

    Cachexia is commonly found in cancer patients and has profound consequences; yet there is only one questionnaire that examines the patient's perspective. To report a rigorously developed module for patient self-reported impact of cancer cachexia. Module development followed published guidelines. Patients from across the cancer cachexia trajectory were included. In Phase 1, health-related quality of life (HRQOL) issues were generated from a literature review and interviews with patients in four countries. The issues were revised based on patient and health care professional (HCP) input. In Phase 2, questionnaire items were formulated and translated into the languages required for Phase 3, the pilot phase, in which patients from eight countries scored the relevance and importance of each item, and provided qualitative feedback. A total of 39 patients and 12 HCPs took part in Phase 1. The literature review produced 68 HRQOL issues, with 22 new issues arising from the patient interviews. After patient and HCP input, 44 issues were formulated into questionnaire items in Phase 2. One hundred ten patients took part in Phase 3. One item was reworded, and 20 items were deleted as a consequence of patient feedback. The QLQ-CAX24 is a cancer cachexia-specific questionnaire, comprising 24 items, for HRQOL assessment in clinical trials and practice. It contains five multi-item scales (food aversion, eating and weight-loss worry, eating difficulties, loss of control, and physical decline) and four single items. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  4. A Key Role for Leukemia Inhibitory Factor in C26 Cancer Cachexia.

    Science.gov (United States)

    Seto, Danielle N; Kandarian, Susan C; Jackman, Robert W

    2015-08-07

    Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling, and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-κB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. LIF was elevated in C26 conditioned medium (CM), but IL-6, OSM, TNFα, and myostatin were not. A LIF-blocking antibody abolished C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and myotube atrophy but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together, these data support an important role of LIF-JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Evaluation of role of telmisartan in combination with 5-fluorouracil in gastric cancer cachexia.

    Science.gov (United States)

    Sukumaran, Shreesha; Patel, Hetal J; Patel, Bhoomika M

    2016-06-01

    The objective of the present study was to evaluate the effect of combination of telmisartan with 5-flourouracil (5-FU) in gastric cancer cachexia induced by administering N-methyl-N'-methyl-N-nitrosoguanidine (MNNG). MNND was administered once daily by oral gavage for two weeks, and saturated NaCl (1ml per rat) was then given once every 3days for 4weeks. 5-FU (75mg/kg, i.v.) was administered once three weeks from 7th to 22nd week. From 7th to 22nd week, telmisartan (5mg/kg, p.o.) was also administered along with 5-FU. MNNG produced significant decrease in food intake, body weight, caused hyperglycemia, dyslipidemia, hypertension worsened hemodyanamics, increased cachexia markers and increased tumor markers like lactate dehydrogenase and γ-glutamyltransferase. MNNG also produced oxidative stress in the stomach tissue. Treatment with combination of telmisartan with 5-FU produced significant increase in food intake and body weight, controlled hyperglycemia and dyslipidemia, preserved hemodynamic function, and decreased the cachexia markers while 5-FU alone did not produce any such effects. Further, the combination of telmisartan with 5-FU significantly reduced tumor marker levels, oxidative stress and also significantly decreased the cell proliferation, apoptosis, hyperkeratosis, keratohyaline granules and invasive carcinoma of forestomach and reduced muscle atrophy in tibilias anterior skeletal muscle. Our data suggests that combination of telmisartan with 5-FU treatment is beneficial in controlling cancer cachexia. Telmisartan can be used as an add-on therapy with 5-FU or other traditional chemotherapeutic agents. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia.

    Science.gov (United States)

    Ihnatko, R; Post, C; Blomqvist, A

    2013-10-01

    Anorexia-cachexia is a common and severe cancer-related complication but the underlying mechanisms are largely unknown. Here, using a mouse model for tumour-induced anorexia-cachexia, we screened for proteins that are differentially expressed in the hypothalamus, the brain's metabolic control centre. The hypothalamus of tumour-bearing mice with implanted methylcholanthrene-induced sarcoma (MCG 101) displaying anorexia and their sham-implanted pair-fed or free-fed littermates was examined using two-dimensional electrophoresis (2-DE)-based comparative proteomics. Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry. The 2-DE data showed an increased expression of dynamin 1, hexokinase, pyruvate carboxylase, oxoglutarate dehydrogenase, and N-ethylmaleimide-sensitive factor in tumour-bearing mice, whereas heat-shock 70 kDa cognate protein, selenium-binding protein 1, and guanine nucleotide-binding protein Gα0 were downregulated. The expression of several of the identified proteins was similarly altered also in the caloric-restricted pair-fed mice, suggesting an involvement of these proteins in brain metabolic adaptation to restricted nutrient availability. However, the expression of dynamin 1, which is required for receptor internalisation, and of hexokinase, and pyruvate carboxylase were specifically changed in tumour-bearing mice with anorexia. The identified differentially expressed proteins may be new candidate molecules involved in the pathophysiology of tumour-induced anorexia-cachexia.

  7. Influence of cancer cachexia on drug liver metabolism and renal elimination in rats

    Science.gov (United States)

    Cvan Trobec, Katja; Kerec Kos, Mojca; Trontelj, Jurij; Grabnar, Iztok; Tschirner, Anika; Palus, Sandra; Anker, Stefan D; Springer, Jochen; Lainscak, Mitja

    2015-01-01

    Background Body wasting and cachexia change body composition and organ function, with effects on drug pharmacokinetics. The aim of this study was to investigate how cancer and cancer cachexia modify liver metabolism and renal drug elimination in rats. Methods Nine male Wistar-Han rats received a single oral dose of midazolam and propranolol (markers of hepatic metabolism), and 10 rats received single intravenous dose of iohexol, a marker of glomerular filtration rate. After drug delivery, multiple dried blood samples were obtained within 2 h post-dose to evaluate drug pharmacokinetic profiles. After baseline sampling (D0), rats were injected with tumour cells. Drug application and blood sampling were repeated when rats developed tumours (Day 5—D5), and when rats were severely cachectic (Day 10—D10). Clearance (CL) and volume of distribution (Vd) of drugs were assessed with non-linear mixed effects modelling. Weight and body composition were measured on D0 and D10 and were related to pharmacokinetic parameters. Results All three drugs showed non-significant trend towards increased CL and Vd on D5. On D10, midazolam and propranolol CL and midazolam Vd significantly decreased from baseline (−80.5%, −79.8%, and −72.0%, respectively, P cachexia, which could increase risk of dose-related adverse events. PMID:26136411

  8. A systematic review and thematic synthesis of quality of life in the informal carers of cancer patients with cachexia.

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    Wheelwright, Sally; Darlington, Anne-Sophie; Hopkinson, Jane B; Fitzsimmons, Deborah; Johnson, Colin

    2016-02-01

    Informal carers of cancer patients with cachexia face additional challenges to those encountered by informal carers in general because of the central role food and eating play in everyday life. Patient weight loss and anorexia, core features of cancer cachexia, are frequent causes of distress in caregivers. Identification of quality of life issues can inform the development of interventions for both caregivers and patients and facilitate communication with healthcare professionals. To identify quality of life issues that are relevant to carers of cancer patients with cachexia. A systematic review and thematic synthesis of the qualitative literature were conducted. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, ISI Web of Knowledge, EMBASE, MEDLINE, CINAHL, PsycINFO and PsycARTICLES were searched for publications dated from January 1980 to February 2015 using search terms relating to cancer, cachexia, quality of life and carers. Papers written in the English language, featuring direct quotes from the carers of adult patients with any cancer diagnosis and cachexia or problems with weight loss or anorexia, were included. Five themes were extracted from the 16 identified studies. These highlighted the impact on everyday life, the attempts of some carers to take charge, the need for healthcare professional's input, conflict with the patient and negative emotions. The complexity of caring for a cancer patient with cachexia translates into a range of problems and experiences for informal carers. By addressing the impact of caring for a patient with cancer cachexia on carers, both caregiver and patient quality of life may improve. © The Author(s) 2015.

  9. Adipose tissue fibrosis in human cancer cachexia: the role of TGFβ pathway.

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    Alves, Michele Joana; Figuerêdo, Raquel Galvão; Azevedo, Flavia Figueiredo; Cavallaro, Diego Alexandre; Neto, Nelson Inácio Pinto; Lima, Joanna Darck Carola; Matos-Neto, Emidio; Radloff, Katrin; Riccardi, Daniela Mendes; Camargo, Rodolfo Gonzalez; De Alcântara, Paulo Sérgio Martins; Otoch, José Pinhata; Junior, Miguel Luiz Batista; Seelaender, Marília

    2017-03-14

    Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGFβ) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGFβ in inducing AT remodeling in weight-losing cancer patients are poorly understood. This study examined the modulation of ECM components mediated by TGFβ pathway in fibrotic AT obtained from cachectic gastrointestinal cancer patients. After signing the informed consent form, patients were enrolled into the following groups: cancer cachexia (CC, n = 21), weight-stable cancer (WSC, n = 17), and control (n = 21). The total amount of collagen and elastic fibers in the subcutaneous AT was assessed by histological analysis and by immunohistochemistry. TGFβ isoforms expression was analyzed by Multiplex assay and by immunohistochemistry. Alpha-smooth muscle actin (αSMA), fibroblast-specific protein (FSP1), Smad3 and 4 were quantified by qPCR and/or by immunohistochemistry. Interleukin (IL) 2, IL5, IL8, IL13 and IL17 content, cytokines known to be associated with fibrosis, was measured by Multiplex assay. There was an accumulation of collagen and elastic fibers in the AT of CC, as compared with WSC and controls. Collagens type I, III, VI, and fibronectin expression was enhanced in the tissue of CC, compared with both WSC and control. The pronounced expression of αSMA in the surrounding of adipocytes, and the increased mRNA content for FSP1 (20-fold) indicate the presence of activated myofibroblasts; particularly in CC. TGFβ1 and TGFβ3 levels were up-regulated by cachexia in AT, as well in the isolated adipocytes. Smad3 and Smad4 labeling was found to be more evident in the fibrotic areas

  10. Weight loss versus muscle loss: re-evaluating inclusion criteria for future cancer cachexia interventional trials.

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    Roeland, Eric J; Ma, Joseph D; Nelson, Sandahl H; Seibert, Tyler; Heavey, Sean; Revta, Carolyn; Gallivan, Andrea; Baracos, Vickie E

    2017-02-01

    Participation in cancer cachexia clinical trials requires a defined weight loss (WL) over time. A loss in skeletal muscle mass, measured by cross-sectional computed tomography (CT) image analysis, represents a possible alternative. Our aim was to compare WL versus muscle loss in patients who were screened to participate in a cancer cachexia clinical trial. This was a single-center, retrospective analysis in metastatic colorectal cancer patients screened for an interventional cancer cachexia trial requiring a ≥5 % WL over the preceding 6 months. Concurrent CT images obtained as part of standard oncology care were analyzed for changes in total muscle and fat (visceral, subcutaneous, and total). Of patients screened (n = 36), 3 (8 %) enrolled in the trial, 17 (47 %) were excluded due to insufficient WL (20 %), and 16 (44 %) met inclusion criteria for WL. Patients who met screening criteria for WL (5-20 %) had a mean ± SD of 7.7 ± 8.7 % muscle loss, 24.4 ± 37.5 % visceral adipose loss, 21.6 ± 22.3 % subcutaneous adipose loss, and 22.1 ± 24.7 % total adipose loss. Patients excluded due to insufficient WL had 2 ± 6.4 % muscle loss, but a gain of 8.5 ± 39.8 % visceral adipose, and 4.2 ± 28.2 % subcutaneous adipose loss and 0.8 ± 28.4 % total adipose loss. Of the patients excluded due to WL 5 %. Defining cancer cachexia by WL over time may be limited as it does not capture skeletal muscle loss. Cross-sectional CT body composition analysis may improve early detection of muscle loss and patient participation in future cancer cachexia clinical trials.

  11. IL-6 regulation on skeletal muscle mitochondrial remodeling during cancer cachexia in the ApcMin/+ mouse

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    White James P

    2012-07-01

    Full Text Available Abstract Background Muscle protein turnover regulation during cancer cachexia is being rapidly defined, and skeletal muscle mitochondria function appears coupled to processes regulating muscle wasting. Skeletal muscle oxidative capacity and the expression of proteins regulating mitochondrial biogenesis and dynamics are disrupted in severely cachectic ApcMin/+ mice. It has not been determined if these changes occur at the onset of cachexia and are necessary for the progression of muscle wasting. Exercise and anti-cytokine therapies have proven effective in preventing cachexia development in tumor bearing mice, while their effect on mitochondrial content, biogenesis and dynamics is not well understood. The purposes of this study were to 1 determine IL-6 regulation on mitochondrial remodeling/dysfunction during the progression of cancer cachexia and 2 to determine if exercise training can attenuate mitochondrial dysfunction and the induction of proteolytic pathways during IL-6 induced cancer cachexia. Methods ApcMin/+ mice were examined during the progression of cachexia, after systemic interleukin (IL-6r antibody treatment, or after IL-6 over-expression with or without exercise. Direct effects of IL-6 on mitochondrial remodeling were examined in cultured C2C12 myoblasts. Results Mitochondrial content was not reduced during the initial development of cachexia, while muscle PGC-1α and fusion (Mfn1, Mfn2 protein expression was repressed. With progressive weight loss mitochondrial content decreased, PGC-1α and fusion proteins were further suppressed, and fission protein (FIS1 was induced. IL-6 receptor antibody administration after the onset of cachexia improved mitochondrial content, PGC-1α, Mfn1/Mfn2 and FIS1 protein expression. IL-6 over-expression in pre-cachectic mice accelerated body weight loss and muscle wasting, without reducing mitochondrial content, while PGC-1α and Mfn1/Mfn2 protein expression was suppressed and FIS1 protein expression

  12. Diet-induced obesity and insulin resistance spur tumor growth and cancer cachexia in rats bearing the Yoshida sarcoma.

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    Honors, Mary Ann; Kinzig, Kimberly P

    2014-01-01

    Obesity and insulin resistance are associated with increased risk of cancer and cancer mortality. However, it is currently unknown whether they contribute to the development of cancer cachexia, a syndrome that contributes significantly to morbidity and mortality in individuals with cancer. The present experiment addresses the question of whether preexisting obesity and insulin resistance alter tumor growth and cancer cachexia symptoms in Yoshida sarcoma bearing male rats. Obesity and insulin resistance were induced through 5 weeks of high-fat (HF) diet feeding and insulin resistance was confirmed by intraperitoneal glucose tolerance testing. Chow-fed animals were used as a control group. Following the establishment of insulin resistance, HF- and chow-fed animals were implanted with fragments of the Yoshida sarcoma or received a sham surgery. Tumor growth rate was greater in HF-fed animals, resulting in larger tumors. In addition, cancer cachexia symptoms developed in HF-fed animals but not chow-fed animals during the 18-day experiment. These results support a stimulatory effect of obesity and insulin resistance on tumor growth and cancer cachexia development in Yoshida sarcoma-bearing rats. Future research should investigate the relationship between obesity, insulin resistance, and cancer cachexia in human subjects.

  13. Expression of CCAAT/Enhancer Binding Protein Beta in Muscle Satellite Cells Inhibits Myogenesis in Cancer Cachexia.

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    François Marchildon

    Full Text Available Cancer cachexia is a paraneoplastic syndrome that causes profound weight loss and muscle mass atrophy and is estimated to be the cause of up to 30% of cancer deaths. Though the exact cause is unknown, patients with cancer cachexia have increased muscle protein catabolism. In healthy muscle, injury activates skeletal muscle stem cells, called satellite cells, to differentiate and promote regeneration. Here, we provide evidence that this mechanism is inhibited in cancer cachexia due to persistent expression of CCAAT/Enhancer Binding Protein beta (C/EBPβ in muscle myoblasts. C/EBPβ is a bzip transcription factor that is expressed in muscle satellite cells and is normally downregulated upon differentiation. However, in myoblasts exposed to a cachectic milieu, C/EBPβ expression remains elevated, despite activation to differentiate, resulting in the inhibition of myogenin expression and myogenesis. In vivo, cancer cachexia results in increased number of Pax7+ cells that also express C/EBPβ and the inhibition of normal repair mechanisms. Loss of C/EBPβ expression in primary myoblasts rescues differentiation under cachectic conditions without restoring myotube size, indicating that C/EBPβ is an important inhibitor of myogenesis in cancer cachexia.

  14. Effect of beta-adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial.

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    Clark, Andrew L; Coats, Andrew J S; Krum, Henry; Katus, Hugo A; Mohacsi, Paul; Salekin, Damien; Schultz, Melissa K; Packer, Milton; Anker, Stefan D

    2017-08-01

    Cardiac cachexia frequently accompanies the progression of heart failure despite the use of effective therapies for left ventricular dysfunction. Activation of the sympathetic nervous system has been implicated in the pathogenesis of weight loss, but the effects of sympathetic antagonism on cachexia are not well defined. We prospectively evaluated changes in body weight in 2289 patients with heart failure who had dyspnoea at rest or on minimal exertion and a left ventricular ejection fraction 6%) (95% confidence interval: 14-48%, P = 0.002) and were 37% more likely to experience a significant gain in weight (≥5%) (95% confidence interval: 12-66%, P = 0.002). Carvedilol's ability to prevent weight loss was most marked in patients with increased body mass index at baseline, whereas its ability to promote weight gain was most marked in patients with decreased body mass index at baseline. Increases in weight were not accompanied by evidence of fluid retention. Baseline values for body mass index and change in body weight were significant predictors of survival regardless of treatment. Carvedilol attenuated the development and promoted a partial reversal of cachexia in patients with severe chronic heart failure, supporting a role for prolonged sympathetic activation in the genesis of weight loss. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  15. Health care professionals' experience, understanding and perception of need of advanced cancer patients with cachexia and their families: The benefits of a dedicated clinic.

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    Scott, David; Reid, Joanne; Hudson, Peter; Martin, Peter; Porter, Sam

    2016-12-30

    Cachexia is defined as the on-going loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support. It is found in up to 80% of patients with advanced cancer and has profound psycho-social consequences for patients and their families. Previous studies demonstrate that many healthcare professionals receive little formal education in cachexia management leading them to feel that they have limited understanding of the syndrome and cannot intervene effectively. This study aims to examine the value of a dedicated cachexia clinic and its influence on staff understanding and practice. An exploratory qualitative study was conducted. The study employed semi-structured interviews with a range of healthcare professionals responsible for designing and delivering cancer care in a large teaching hospital in Australia. This hospital had a dedicated cachexia clinic. In-depth interviews were conducted with 8 healthcare professionals and senior managers. Four themes were identified: formal and informal education; knowledge and understanding; truth telling in cachexia and palliative care; and, a multi-disciplinary approach. Findings show that improved knowledge and understanding across a staff body can lead to enhanced staff confidence and a willingness to address cancer cachexia and its consequences with patients and their families. Comparisons with similar previous research demonstrate the advantages of providing a structure for staff to gain knowledge about cachexia and how this can contribute to feelings of improved understanding and confidence necessary to respond to the challenge of cachexia.

  16. Identification and functional analysis of a potential key lncRNA involved in fat loss of cancer cachexia.

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    Liu, Huiquan; Zhou, Ting; Wang, Bangyan; Li, Lu; Ye, Dawei; Yu, Shiying

    2018-02-01

    Cancer cachexia is a devastating, multifactorial, and irreversible syndrome characterized by skeletal muscle reduction with or without fat loss. Although much attention has been focused on muscle wasting, fat loss may occur earlier and accelerate muscle wasting in cachexia. The cause of 20% of cancer related death makes it urgent to discover molecular mechanisms behind cancer cachexia. Here we applied weighted gene co-expression network analysis (WGCNA) to identify cachexia related gene modules using differentially expressed 3289 genes and 59 long non-coding RNAs based on microarray data of cachectic and non-cachectic subcutaneous adipose tissue. Subsequently, 16 independent modules were acquired and GSAASeqSP Toolset confirmed that black module was significantly associated with fat loss in cancer cachexia. Top 50 hub-genes in black module contained only one lncRNA, VLDLR antisense RNA 1 (VLDLR-AS1). We then explored the function of black module from the view of VLDLR-AS1-connected genes in the network. GO enrichment and KEGG pathways analysis revealed LDLR-AS1-connected genes were involved in Wnt signaling pathway, small GTPase mediated signal transduction, epithelial-mesenchymal transition and so on. Through construction of competing endogenous RNAs (ceRNAs) regulation network, we showed that VLDLR-AS1 may function with hsa-miR-600 to regulate gene GOLGA3, DUSP14, and UCHL1, or interact with hsa-miR-1224-3p to modulate the expression of gene GOLGA3, ZNF219, RNF141, and CALU. After literature validation, we predicted that VLDLR-AS1 most likely interacted with miR-600 to regulate UCH-L1 through Wnt/β-catenin signaling pathway. However, further experiments are still required to validate mechanisms of VLDLR-AS1 in fat reduction of cancer cachexia. © 2017 Wiley Periodicals, Inc.

  17. Cancer cachexia-induced muscle atrophy: evidence for alterations in microRNAs important for muscle size.

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    Lee, David E; Brown, Jacob L; Rosa-Caldwell, Megan E; Blackwell, Thomas A; Perry, Richard A; Brown, Lemuel A; Khatri, Bhuwan; Seo, Dongwon; Bottje, Walter G; Washington, Tyrone A; Wiggs, Michael P; Kong, Byung-Whi; Greene, Nicholas P

    2017-05-01

    Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy; however, less is known specifically on miRNAs in cancer cachexia. The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition. Phosphate-buffered saline (PBS) or Lewis lung carcinoma cells (LLC) were injected into C57BL/6J mice at 8 wk of age. LLC animals were allowed to develop tumors for 4 wk to induce cachexia. Tibialis anterior muscles were extracted and processed to isolate small RNAs, which were used for miRNA sequencing. Sequencing results were assembled with mature miRNAs, and functions of miRNAs were analyzed by Ingenuity Pathway Analysis. LLC animals developed tumors that contributed to significantly smaller tibialis anterior muscles (18.5%) and muscle cross-sectional area (40%) compared with PBS. We found 371 miRNAs to be present in the muscle above background levels. Of these, nine miRNAs were found to be differentially expressed. Significantly altered groups of miRNAs were categorized into primary functionalities including cancer, cell-to-cell signaling, and cellular development among others. Gene network analysis predicted specific alterations of factors contributing to muscle size including Akt, FOXO3, and others. These results create a foundation for future research into the sufficiency of targeting these genes to attenuate muscle loss in cancer cachexia. Copyright © 2017 the American Physiological Society.

  18. Intestinal congestion and right ventricular dysfunction: a link with appetite loss, inflammation, and cachexia in chronic heart failure.

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    Valentova, Miroslava; von Haehling, Stephan; Bauditz, Juergen; Doehner, Wolfram; Ebner, Nicole; Bekfani, Tarek; Elsner, Sebastian; Sliziuk, Veronika; Scherbakov, Nadja; Murín, Ján; Anker, Stefan D; Sandek, Anja

    2016-06-01

    Mechanisms leading to cachexia in heart failure (HF) are not fully understood. We evaluated signs of intestinal congestion in patients with chronic HF and their relationship with cachexia. Of the 165 prospectively enrolled outpatients with left ventricular ejection fraction ≤40%, 29 (18%) were cachectic. Among echocardiographic parameters, the combination of right ventricular dysfunction and elevated right atrial pressure (RAP) provided the best discrimination between cachectic and non-cachectic patients [area under the curve 0.892, 95% confidence interval (CI): 0.832-0.936]. Cachectic patients, compared with non-cachectic, had higher prevalence of postprandial fullness, appetite loss, and abdominal discomfort. Abdominal ultrasound showed a larger bowel wall thickness (BWT) in the entire colon and terminal ileum in cachectic than in non-cachectic patients. Bowel wall thickness correlated positively with gastrointestinal symptoms, high-sensitivity C-reactive protein, RAP, and truncal fat-free mass, the latter serving as a marker of the fluid content. Logistic regression analysis showed that BWT was associated with cachexia, even after adjusting for cardiac function, inflammation, and stages of HF (odds ratio 1.4, 95% CI: 1.0-1.8; P-value = 0.03). Among the cardiac parameters, only RAP remained significantly associated with cachexia after multivariable adjustment. Cardiac cachexia was associated with intestinal congestion irrespective of HF stage and cardiac function. Gastrointestinal discomfort, appetite loss, and pro-inflammatory activation provide probable mechanisms, by which intestinal congestion may trigger cardiac cachexia. However, our results are preliminary and larger studies are needed to clarify the intrinsic nature of this relationship. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  19. ACT-ONE - ACTION at last on cancer cachexia by adapting a novel action beta-blocker.

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    Lainscak, Mitja; Laviano, Alessandro

    2016-09-01

    Novel action beta-blockers combine many different pharmacological effects. The espindolol exhibits effects through β and central 5-HT1α receptors to demonstrate pro-anabolic, anti-catabolic, and appetite-stimulating actions. In the ACT-ONE trial, espindolol reversed weight loss and improved handgrip strength in patients with cachexia due to non-small cell lung cancer or colorectal cancer. With this trial, another frontier of cachexia management is in sight. Nonetheless, more efficacy and safety data is needed before new therapeutic indications for novel action beta-blockers can be endorsed.

  20. The Relationship between Sarcopenia and Systemic Inflammatory Response for Cancer Cachexia in Small Cell Lung Cancer.

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    Eun Young Kim

    Full Text Available The prognostic significance of sarcopenia, an important component of cancer cachexia, has been demonstrated in oncologic patients. Catabolic drivers have been suggested to be key features of cancer cachexia.To determine the relationship between systemic inflammatory markers and CT-determined muscle mass in patients with SCLC.Cross-sectional muscle areas were evaluated at the level of the third lumbar vertebra (L3 using baseline CT images in 186 SCLC patients. Sarcopenia was defined as a L3 muscle index (L3MI, muscle area at L3/height2 of < 55 cm2/m2 for men and of < 39 cm2/m2 for women. Systemic inflammatory markers investigated included serum white blood cell count (WBC, neutrophil: lymphocyte ratio (NLR, C-reactive protein (CRP, and albumin.Mean L3MI was 47.9 ± 9.7 cm2/m2 for men and 41.6 ± 7.0 cm2/m2 for women. Sarcopenia was present in 128 patients (68.8%, and sarcopenic patients had significant serum lymphocyte counts and albumin levels (p = 0.002 and 0.041, respectively, and higher NLRs and CRP levels (p = 0.011 and 0.026 than non-sarcopenic patients. Multivariable analysis revealed that CRP independently predicted L3MI (β = -0.208; 95% CI, -0.415 to -0.002; p = 0.048, along with gender and BMI (p values < 0.001 and performance status (p = 0.010.The present study confirms a significant linear relationship exists between CT-determined muscle mass and CRP in SCLC patients. This association might provide a better understanding of the mechanism of cancer cachexia.

  1. Transmission of chronic wasting disease identifies a prion strain causing cachexia and heart infection in hamsters.

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    Richard A Bessen

    Full Text Available Chronic wasting disease (CWD is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrP(Sc, prion infection of the central and peripheral neuroendocrine system, and PrP(Sc deposition in cardiac muscle. There was also prominent PrP(Sc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the 'wasting' or WST strain of hamster CWD.

  2. Caquexia associada à insuficiência cardíaca Heart failure-induced cachexia

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    Marina Politi Okoshi

    2013-05-01

    Full Text Available Pacientes com insuficiência cardíaca frequentemente desenvolvem estado de caquexia, que constitui fator independente de redução da sobrevida. Caquexia pode ser diagnosticada quando ocorre perda de peso corporal maior que 6% do peso habitual, na ausência de outras doenças. Embora sua fisiopatologia não esteja completamente esclarecida, vários fatores parecem estar envolvidos, como diminuição da ingestão alimentar, anormalidades do trato gastrointestinal, ativação imunológica e neuro-hormonal e alteração da relação entre processos anabólicos e catabólicos. Como não há terapia específica para a caquexia associada à insuficiência cardíaca, o tratamento baseia-se no suporte nutricional, bloqueio neuro-hormonal, controle do edema e anemia e exercícios físicos. Fármacos com propriedades imunomodulatórias e anabólicas encontram-se em investigação clínica e experimental.Heart failure patients often develop cachexia, which is an independent factor for survival reduction. Cachexia can be diagnosed when there is loss of more than 6% of the body weight, in the absence of other diseases. Even though its pathophysiology has not yet been completely clarified, various factors seem to be involved, such as reduction in food consumption, gastrointestinal tract abnormalities, immunologic and neuro-hormonal activarion and changes in the relationship between anabolic and catabolic processes. Since there is not specific therapy for heart failure-induced cachexia, management is based on nutritional support, neuro-hormonal blockade, control of edema and anemia and exercise. Drugs with anabolic and immunomodulating properties are being evaluated and clinical and non-clinical trials.

  3. The clinical picture of cachexia: a mosaic of different parameters (experience of 503 patients).

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    Schwarz, S; Prokopchuk, O; Esefeld, K; Gröschel, S; Bachmann, J; Lorenzen, S; Friess, H; Halle, M; Martignoni, M E

    2017-02-14

    Despite our growing knowledge about the pathomechanisms of cancer cachexia, a whole clinical picture of the cachectic patient is still missing. Our objective was to evaluate the clinical characteristics in cancer patients with and without cachexia to get the whole picture of a cachectic patient. Cancer patients of the University Clinic "Klinikum rechts der Isar" with gastrointestinal, gynecological, hematopoietic, lung and some other tumors were offered the possibility to take part in the treatment concept including a nutrition intervention and an individual training program according to their capability. We now report on the first 503 patients at the time of inclusion in the program between March 2011 and October 2015. We described clinical characteristics such as physical activity, quality of life, clinical dates and food intake. Of 503 patients with cancer, 131 patients (26.0%) were identified as cachectic, 369 (73.4%) as non-cachectic. The change in cachexia were 23% reduced capacity performance (108 Watt for non-cachectic-patients and 83 Watt for cachectic patients) and 12% reduced relative performance (1.53 Watt/kg for non-cachectic and 1.34 Watt/kg for cachectic patients) in ergometry test. 75.6% of non-cachectic and 54.3% of cachectic patients still received curative treatment. Cancer cachectic patients have multiple symptoms such as anemia, impaired kidney function and impaired liver function with elements of mild cholestasis, lower performance and a poorer quality of life in the EORTC questionnaire. Our study reveals biochemical and clinical specific features of cancer cachectic patients.

  4. Altered mitochondrial quality control signaling in muscle of old gastric cancer patients with cachexia.

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    Marzetti, Emanuele; Lorenzi, Maria; Landi, Francesco; Picca, Anna; Rosa, Fausto; Tanganelli, Fabiana; Galli, Marco; Doglietto, Giovanni Battista; Pacelli, Fabio; Cesari, Matteo; Bernabei, Roberto; Calvani, Riccardo; Bossola, Maurizio

    2017-01-01

    Mitochondrial dysfunction is involved in the loss of muscle featuring both aging and cancer cachexia (CC). Whether mitochondrial quality control (MQC) is altered in skeletal myocytes of old patients with CC is unclear. The present investigation therefore sought to preliminarily characterize MQC pathways in muscle of old gastric cancer patients with cachexia. The study followed a case-control cross-sectional design. Intraoperative biopsies of the rectus abdominis muscle were obtained from 18 patients with gastric adenocarcinoma (nine with CC and nine non-cachectic) and nine controls, and assayed for the expression of a set of MQC mediators. The mitofusin 2 expression was reduced in cancer patients compared with controls, independent of CC. Fission protein 1 was instead up-regulated in CC patients relative to the other groups. The mitophagy regulators PTEN-induced putative kinase 1 and Parkin were both down-regulated in cancer patients compared with controls. The ratio between the protein content of the lipidated and non-lipidated forms of microtubule-associated protein 1 light chain 3B was lower in CC patients relative to controls and non-cachectic cancer patients. Finally, the expression of autophagy-associated protein 7, lysosome-associated membrane protein 2, peroxisome proliferator-activated receptor-γ coactivator-1α, and mitochondrial transcription factor A was unvarying among groups. Collectively, our findings indicate that, in old patients with gastric cancer, cachexia is associated with derangements of the muscular MQC axis at several checkpoints: mitochondrial dynamics, mitochondrial tagging for disposal, and mitophagy signaling. Further investigations are needed to corroborate these preliminary findings and determine whether MQC pathways may become target for future interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Association of cardiac cachexia and atrial fibrillation in heart failure patients.

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    Arámbula-Garza, Estefanía; Castillo-Martínez, Lilia; González-Islas, Dulce; Orea-Tejeda, Arturo; Santellano-Juárez, Brenda; Keirns-Davies, Candace; Peláez-Hernández, Viridiana; Sánchez-Santillán, Rocío; Pineda-Juárez, Juan; Cintora-Martínez, Carlos; Pablo-Santiago, Ruth

    2016-11-15

    Cachexia is a common complication in patients with advanced heart failure (HF) associated with inflammatory response activation. Atrial fibrillation (AF) is the most frequent arrhythmia (26%), probably both exacerbate the cardiac cachexia (CC). Evaluate the association of cardiac cachexia and atrial fibrillation in heart failure patients. In a case control study, CC was diagnosed by electrical bioimpedance with vectorial analysis (BIVA). Subjects with congenital heart disease, cancer, HIV, drug use and other causes than HF were excluded. Of the 359 subjects analyzed (men: 52.9%) median age 65years (55-74). Those with CC were older [72 (61-67)] vs. without [62 (52-70) years old, p<0.01]. During follow-up 47.8% of subjects developed CC and 17.27% AF, this was significantly more frequent in cachectic patients CC (23% vs 12.11%, OR: 2.17, 95% CI: 1.19-4.01, p=0.006). Subjects, with AF had lower left ventricular ejection fraction (25.49±12.96 vs. 32.01±15.02, p=0.08), lower posterior wall thickness (10.03±2.12 vs. 11.00±2.47, p=0.007), larger diameter of the left atrium (49.87±9.84 vs. 42.66±7.56, p<0.001), and a higher prevalence of CC (85.42% vs. 69.77%, p=0.028). The 50.58% of was in NYHA class I. In NYHA III, 22.95% were in AF vs. 12.10% with not AF (p=0.027). The frequent coexistence of CC and AF as HF complications indicate greater severity of HF, regardless of its type of HF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Clinical classification of cancer cachexia: phenotypic correlates in human skeletal muscle.

    Science.gov (United States)

    Johns, Neil; Hatakeyama, Shinji; Stephens, Nathan A; Degen, Martin; Degen, Simone; Frieauff, Wilfried; Lambert, Christian; Ross, James A; Roubenoff, Ronenn; Glass, David J; Jacobi, Carsten; Fearon, Kenneth C H

    2014-01-01

    Cachexia affects the majority of patients with advanced cancer and is associated with a reduction in treatment tolerance, response to therapy, and duration of survival. One impediment towards the effective treatment of cachexia is a validated classification system. 41 patients with resectable upper gastrointestinal (GI) or pancreatic cancer underwent characterisation for cachexia based on weight-loss (WL) and/or low muscularity (LM). Four diagnostic criteria were used >5%WL, >10%WL, LM, and LM+>2%WL. All patients underwent biopsy of the rectus muscle. Analysis included immunohistochemistry for fibre size and type, protein and nucleic acid concentration, Western blots for markers of autophagy, SMAD signalling, and inflammation. Compared with non-cachectic cancer patients, patients with LM or LM+>2%WL, mean muscle fibre diameter was reduced by about 25% (p = 0.02 and p = 0.001 respectively). No significant difference in fibre diameter was observed if patients had WL alone. Regardless of classification, there was no difference in fibre number or proportion of fibre type across all myosin heavy chain isoforms. Mean muscle protein content was reduced and the ratio of RNA/DNA decreased in patients with either >5%WL or LM+>2%WL. Compared with non-cachectic patients, SMAD3 protein levels were increased in patients with >5%WL (p = 0.022) and with >10%WL, beclin (p = 0.05) and ATG5 (p = 0.01) protein levels were increased. There were no differences in phospho-NFkB or phospho-STAT3 levels across any of the groups. Muscle fibre size, biochemical composition and pathway phenotype can vary according to whether the diagnostic criteria for cachexia are based on weight loss alone, a measure of low muscularity alone or a combination of the two. For intervention trials where the primary end-point is a change in muscle mass or function, use of combined diagnostic criteria may allow identification of a more homogeneous patient cohort, reduce the sample size required

  7. Clinical classification of cancer cachexia: phenotypic correlates in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Neil Johns

    Full Text Available BACKGROUND: Cachexia affects the majority of patients with advanced cancer and is associated with a reduction in treatment tolerance, response to therapy, and duration of survival. One impediment towards the effective treatment of cachexia is a validated classification system. METHODS: 41 patients with resectable upper gastrointestinal (GI or pancreatic cancer underwent characterisation for cachexia based on weight-loss (WL and/or low muscularity (LM. Four diagnostic criteria were used >5%WL, >10%WL, LM, and LM+>2%WL. All patients underwent biopsy of the rectus muscle. Analysis included immunohistochemistry for fibre size and type, protein and nucleic acid concentration, Western blots for markers of autophagy, SMAD signalling, and inflammation. FINDINGS: Compared with non-cachectic cancer patients, patients with LM or LM+>2%WL, mean muscle fibre diameter was reduced by about 25% (p = 0.02 and p = 0.001 respectively. No significant difference in fibre diameter was observed if patients had WL alone. Regardless of classification, there was no difference in fibre number or proportion of fibre type across all myosin heavy chain isoforms. Mean muscle protein content was reduced and the ratio of RNA/DNA decreased in patients with either >5%WL or LM+>2%WL. Compared with non-cachectic patients, SMAD3 protein levels were increased in patients with >5%WL (p = 0.022 and with >10%WL, beclin (p = 0.05 and ATG5 (p = 0.01 protein levels were increased. There were no differences in phospho-NFkB or phospho-STAT3 levels across any of the groups. CONCLUSION: Muscle fibre size, biochemical composition and pathway phenotype can vary according to whether the diagnostic criteria for cachexia are based on weight loss alone, a measure of low muscularity alone or a combination of the two. For intervention trials where the primary end-point is a change in muscle mass or function, use of combined diagnostic criteria may allow identification of a more

  8. Cachexia but not obesity worsens the postoperative outcome after pancreatoduodenectomy in pancreatic cancer.

    Science.gov (United States)

    Pausch, Thomas; Hartwig, Werner; Hinz, Ulf; Swolana, Thomas; Bundy, Bogota D; Hackert, Thilo; Grenacher, Lars; Büchler, Markus W; Werner, Jens

    2012-09-01

    Prognosis after pancreatoduodenectomy for pancreatic cancer is determined by tumor characteristics, completeness of resection, and patient's comorbidity. Our aim was to assess the effects of body mass and fat distribution on the postoperative course after pancreatoduodenectomy. Of 2,968 pancreatic resections, 408 patients with primary pancreatic adenocarcinoma who underwent pancreatoduodenectomy and of whom cross sectional images were available were identified and followed-up in a prospective database. Preoperative computed tomographic or magnetic resonance imaging scans were analyzed for abdominal wall fat, hip girdle fat, visceral fat, and abdominal depth. Peri- and postoperative parameters, including preoperative unintentional weight loss, cachexia-associated serum parameters, nonoperative and operative complications, and mortality and long-term survival were evaluated and correlated with body mass index and fat distribution. Patients with low body mass index had a greater 90-day mortality (P = .048) and a trend toward greater complication rates and in-hospital mortality, despite a greater comorbidity in obese patients with a higher body mass index. Accordingly, patients with large amounts of abdominal wall fat had fewer intra-abdominal abscesses (P = .047), lower in-hospital (P = .019) and 90-day mortality rates (P = .007), and better long-term survival (P = .016). In pancreatic cancer, underweight but not obese patients have a poor outcome after pancreatoduodenectomy. This observation emphasizes the need for pre- and perioperative therapeutic improvements in the setting of pancreatic cancer-associated cachexia. Copyright © 2012 Mosby, Inc. All rights reserved.

  9. Malnutrition, anorexia and cachexia in cancer patients: A mini-review on pathogenesis and treatment.

    Science.gov (United States)

    Nicolini, Andrea; Ferrari, Paola; Masoni, Maria Chiara; Fini, Milena; Pagani, Stefania; Giampietro, Ottavio; Carpi, Angelo

    2013-10-01

    Malnutrition, anorexia and cachexia are a common finding in cancer patients. They become more evident with tumor growth and spread. However, the mechanisms by which they are sustained often arise early in the history of cancer. For malnutrition, these mechanisms can involve primary tumor or damage by specific treatment such as anticancer therapies (surgery, chemotherapy, radiotherapy) also in cancers that usually are not directly responsible for nutritional and metabolic status alterations (i.e. bone tumors). For anorexia, meal-related neural or hormonal signals and humoral signals related to body fat or energy storage and the interaction of these signals with the hypothalamus or the hypothalamic inappropriate response play a pathogenetic role. Some cytokines are probably involved in these mechanisms. For cachexia, the production of proinflammatory cytokines by tumour cells is the initial mechanism; the main biochemical mechanisms involved include the ubiquitine proteasome-dependent proteolysis and heat shock proteins. Treatment includes pharmaceutical and nutritional interventions. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Adipose tissue volume is decreased in recently diagnosed cancer patients with cachexia.

    Science.gov (United States)

    Agustsson, Thorhallur; Wikrantz, Pal; Rydén, Mikael; Brismar, Torkel; Isaksson, Bengt

    2012-09-01

    Approximately 50% of patients with cancer develop cachexia. The aim of the present study was to determine if there were differences in the amount of visceral and subcutaneous adipose tissues at the time of the diagnosis among patients with cancer cachexia (CC), patients with cancer and a stable weight (WS), and patients with cancer and weight loss because of gastrointestinal obstruction (GO). Patients with recently diagnosed cancer were divided into the CC, WS, and GO groups. Body composition was determined by bioimpedance. Basal metabolic rate and energy expenditure were estimated by indirect calorimetry. Visceral and subcutaneous white adipose tissues (WATs) were quantified by the segmentation of a 10-mm-thick computed tomographic slice obtained through the central part of the third lumbar vertebra. The body mass index and body fat were decreased in the CC and GO groups compared with the WS group, but there were no significant differences between the two weight-losing groups. Lean body mass, total body water, and energy expenditure were similar among the groups. The visceral WAT volume was decreased in the CC but not in the GO group compared with the WS group (P new information regarding the WAT distribution in CC. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Prevention of liver cancer cachexia-induced cardiac wasting and heart failure

    Science.gov (United States)

    Springer, Jochen; Tschirner, Anika; Haghikia, Arash; von Haehling, Stephan; Lal, Hind; Grzesiak, Aleksandra; Kaschina, Elena; Palus, Sandra; Pötsch, Mareike; von Websky, Karoline; Hocher, Berthold; Latouche, Celine; Jaisser, Frederic; Morawietz, Lars; Coats, Andrew J.S.; Beadle, John; Argiles, Josep M.; Thum, Thomas; Földes, Gabor; Doehner, Wolfram; Hilfiker-Kleiner, Denise; Force, Thomas; Anker, Stefan D.

    2014-01-01

    Aims Symptoms of cancer cachexia (CC) include fatigue, shortness of breath, and impaired exercise capacity, which are also hallmark symptoms of heart failure (HF). Herein, we evaluate the effects of drugs commonly used to treat HF (bisoprolol, imidapril, spironolactone) on development of cardiac wasting, HF, and death in the rat hepatoma CC model (AH-130). Methods and results Tumour-bearing rats showed a progressive loss of body weight and left-ventricular (LV) mass that was associated with a progressive deterioration in cardiac function. Strikingly, bisoprolol and spironolactone significantly reduced wasting of LV mass, attenuated cardiac dysfunction, and improved survival. In contrast, imidapril had no beneficial effect. Several key anabolic and catabolic pathways were dysregulated in the cachectic hearts and, in addition, we found enhanced fibrosis that was corrected by treatment with spironolactone. Finally, we found cardiac wasting and fibrotic remodelling in patients who died as a result of CC. In living cancer patients, with and without cachexia, serum levels of brain natriuretic peptide and aldosterone were elevated. Conclusion Systemic effects of tumours lead not only to CC but also to cardiac wasting, associated with LV-dysfunction, fibrotic remodelling, and increased mortality. These adverse effects of the tumour on the heart and on survival can be mitigated by treatment with either the β-blocker bisoprolol or the aldosterone antagonist spironolactone. We suggest that clinical trials employing these agents be considered to attempt to limit this devastating complication of cancer. PMID:23990596

  12. Reversible and cachexia-associated feline skin fragility syndrome in three cats.

    Science.gov (United States)

    Furiani, Nicla; Porcellato, Ilaria; Brachelente, Chiara

    2017-10-01

    Feline skin fragility syndrome (FSFS) is an acquired disorder characterized by altered collagen production resulting in an extremely thin and fragile skin. FSFS is associated with diseases characterized by excessive steroidal hormones that can inhibit collagen synthesis. It is also described concomitantly with severe inflammatory, infectious or neoplastic conditions where the pathogenesis remains largely unknown. To describe three cases of FSFS in cats that become cachectic secondary to different causes without glucocorticoid involvement. To describe the histopathological features of connective tissue for both fragile skin and the skin after healing. All cats developed cachexia in less than two months (body condition score ranging from 1-1.5). Concomitant diseases were diagnosed in Case 1 (aspiration pneumonia due to mega-oesophagus) and Case 2 (feline immunodeficiency virus (FIV)). In Case 3, malnutrition was suspected as a primary cause. The main histological feature of fragile skin was an atrophic dermis with pale eosinophilic, thin and irregular collagen fibres with numerous red cores observed with Masson's stain. Elastic fibres were normal. Postrecovery histopathological findings at 11 (Case 1) and six months (Case 3) after diagnosis, indicated normalization of the collagen and of the whole skin as compared with controls. To the best of the authors' knowledge, this is the first report describing a reversible, nonsteroid-induced FSFS, associated with rapidly developing cachexia in cats. © 2017 ESVD and ACVD.

  13. Anorexia-cachexia syndrome in pancreatic cancer: recent advances and new pharmacological approach.

    Science.gov (United States)

    Ronga, Ilaria; Gallucci, Fernando; Riccardi, Ferdinando; Uomo, Generoso

    2014-03-01

    About 80% of all pancreatic ductal adenocarcinoma patients suffer from a wasting syndrome referred to as the "cancer anorexia-cachexia syndrome" (CACS) characterized by abnormally low weight, weakness and loss of skeletal muscle mass with or without loss of body fat, which directly impacts overall survival, quality of life, and physical activity. The aim of this review was to examine recent findings about CACS' pathophysiology and to describe the current pharmacological approaches. In recent years many efforts were made to improve our knowledge of CACS; currently we know that cachexia arises from a complex and multifactorial interaction between various mechanisms including inflammation, anorexia/malnutrition, alterations of protein and lipid metabolism; consequently its management requires multidisciplinary and multipharmacological approach that should address the different causes underlying this clinical event. On these premises, several drugs have been proposed starting from the first pharmacological treatment based on progestational agents or corticosteroids; most of them are in the preclinical phase, but some have already reached the clinical experimentation stage. In conclusion, to date, there is no standard effective treatment and further studies are needed to unravel the basic mechanisms underlying CACS and to develop newer therapeutic strategies with the hope to improve the quality of life of pancreatic cancer patients. Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. A systematic review to establish health-related quality-of-life domains for intervention targets in cancer cachexia.

    Science.gov (United States)

    Wheelwright, S J; Darlington, A-S; Hopkinson, J B; Fitzsimmons, D; White, A; Johnson, C D

    2016-09-01

    To develop a model of the impact of cancer cachexia on patients by identifying the relevant health-related quality-of-life (HRQOL) issues, and to use the model to identify opportunities for intervention. Standard systematic review methods were followed to identify papers which included direct quotes from cancer patients with cachexia or problems with eating or weight loss. Following thematic synthesis methodology, the quotes were coded, and themes and metathemes were extracted. The metathemes were used to develop a model of the patient's experience of cachexia. 18 relevant papers were identified which, in total, contained interviews with more than 250 patients. 226 patient quotes were extracted from the papers and 171 codes. 26 themes and 8 metathemes were formulated. The model developed from the metathemes demonstrated a direct link between eating and food problems and negative emotions and also a link mediated by the associated physical decline. These links provide opportunities for interventions. There are a vast number of HRQOL issues associated with cancer cachexia as identified from patients' own words. The model generated from these issues indicates that relationships, coping and knowledge of the condition are important components of new psychosocial interventions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Is there a relation between pre-sarcopenia, sarcopenia, cachexia and osteoporosis in patients with ankylosing spondylitis?

    Science.gov (United States)

    El Maghraoui, Abdellah; Ebo'o, François Bertin; Sadni, Siham; Majjad, Abderrahim; Hamza, Toufik; Mounach, Aziza

    2016-07-11

    Osteoporosis is a well-known complication of ankylosing spondylitis (AS). However, data about body composition modifications and muscle performance showed conflicting results. The aim of the study was to determine the prevalence and risk factors of pre-sarcopenia, sarcopenia and cachexia in patients with AS and analyze its relationship with bone loss and symptomatic and severity parameters of the disease. Sixty-seven consecutive male patients with AS (mean age of 40.9 ± 11.0 years) and 67 healthy controls were studied. Body composition and bone mineral density (BMD) scans were obtained using DXA. The fat-free mass index (FFMI; fat-free mass divided by height squared) and the percent of fat mass (%FM) were calculated. Pre-sarcopenia was defined by low skeletal muscle mass (SMI 10 s) and cachexia by a BMI 5 mg/l, SMI cachexia, and osteoporosis prevalences were (50.4, 34.3, 11.9, and 16.0) respectively. Patients had a mean 3 kg significant decrease in FFM and a 1 kg/m(2) decrease in appendicular mass vs. healthy controls. Pre-sarcopenia, sarcopenia and cachexia were significantly associated to higher BASDAI levels and low BMD. Our study showed that men with AS had a statistically significant reduction in total and appendicular lean mass that is related to higher disease activity and significantly associated to bone loss.

  16. Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin‐induced cachexia

    Science.gov (United States)

    Conte, Elena; Camerino, Giulia Maria; Mele, Antonietta; De Bellis, Michela; Pierno, Sabata; Rana, Francesco; Fonzino, Adriano; Caloiero, Roberta; Rizzi, Laura; Bresciani, Elena; Ben Haj Salah, Khoubaib; Fehrentz, Jean‐Alain; Martinez, Jean; Giustino, Arcangela; Mariggiò, Maria Addolorata; Coluccia, Mauro; Tricarico, Domenico; Lograno, Marcello Diego; De Luca, Annamaria; Torsello, Antonio; Conte, Diana

    2017-01-01

    Abstract Background Cachexia is a wasting condition associated with cancer types and, at the same time, is a serious and dose‐limiting side effect of cancer chemotherapy. Skeletal muscle loss is one of the main characteristics of cachexia that significantly contributes to the functional muscle impairment. Calcium‐dependent signaling pathways are believed to play an important role in skeletal muscle decline observed in cachexia, but whether intracellular calcium homeostasis is affected in this situation remains uncertain. Growth hormone secretagogues (GHS), a family of synthetic agonists of ghrelin receptor (GHS‐R1a), are being developed as a therapeutic option for cancer cachexia syndrome; however, the exact mechanism by which GHS interfere with skeletal muscle is not fully understood. Methods By a multidisciplinary approach ranging from cytofluorometry and electrophysiology to gene expression and histology, we characterized the calcium homeostasis in fast‐twitch extensor digitorum longus (EDL) muscle of adult rats with cisplatin‐induced cachexia and established the potential beneficial effects of two GHS (hexarelin and JMV2894) at this level. Additionally, in vivo measures of grip strength and of ultrasonography recordings allowed us to evaluate the functional impact of GHS therapeutic intervention. Results Cisplatin‐treated EDL muscle fibres were characterized by a ~18% significant reduction of the muscle weight and fibre diameter together with an up‐regulation of atrogin1/Murf‐1 genes and a down‐regulation of Pgc1‐a gene, all indexes of muscle atrophy, and by a two‐fold increase in resting intracellular calcium, [Ca2+]i, compared with control rats. Moreover, the amplitude of the calcium transient induced by caffeine or depolarizing high potassium solution as well as the store‐operated calcium entry were ~50% significantly reduced in cisplatin‐treated rats. Calcium homeostasis dysregulation parallels with changes of functional ex vivo

  17. Blockade of the IL-6 trans-signalling/STAT3 axis suppresses cachexia in Kras-induced lung adenocarcinoma.

    Science.gov (United States)

    Miller, A; McLeod, L; Alhayyani, S; Szczepny, A; Watkins, D N; Chen, W; Enriori, P; Ferlin, W; Ruwanpura, S; Jenkins, B J

    2017-05-25

    Lung cancer is the leading cause of cancer death worldwide, and is frequently associated with the devastating paraneoplastic syndrome of cachexia. The potent immunomodulatory cytokine interleukin (IL)-6 has been linked with the development of lung cancer as well as cachexia; however, the mechanisms by which IL-6 promotes muscle wasting in lung cancer cachexia are ill-defined. In this study, we report that the gp130F/F knock-in mouse model displaying hyperactivation of the latent transcription factor STAT3 via the common IL-6 cytokine family signalling receptor, gp130, develops cachexia during Kras-driven lung carcinogenesis. Specifically, exacerbated weight loss, early mortality and reduced muscle and adipose tissue mass were features of the gp130F/F:KrasG12D model, but not parental KrasG12D mice in which STAT3 was not hyperactivated. Gene expression profiling of muscle tissue in cachectic gp130F/F:KrasG12D mice revealed the upregulation of IL-6 and STAT3-target genes compared with KrasG12D muscle tissue. These cachectic features of gp130F/F:KrasG12D mice were abrogated upon the genetic normalization of STAT3 activation or ablation of IL-6 in gp130F/F:KrasG12D:Stat3-/+ or gp130F/F:KrasG12D:Il6-/- mice, respectively. Furthermore, protein levels of the soluble IL-6 receptor (sIL-6R), which is the central facilitator of IL-6 trans-signalling, were elevated in cachectic muscle from gp130F/F:KrasG12D mice, and the specific blockade of IL-6 trans-signalling, but not classical signalling, with an anti-IL-6R antibody ameliorated cachexia-related characteristics in gp130F/F:KrasG12D mice. Collectively, these preclinical findings identify trans-signalling via STAT3 as the signalling modality by which IL-6 promotes muscle wasting in lung cancer cachexia, and therefore support the clinical evaluation of the IL-6 trans-signalling/STAT3 axis as a therapeutic target in advanced lung cancer patients presenting with cachexia.

  18. The role of a disturbed arginine/NO metabolism in the onset of cancer cachexia: a working hypothesis.

    Science.gov (United States)

    Buijs, N; Luttikhold, J; Houdijk, A P J; van Leeuwen, P A M

    2012-01-01

    Cancer cachexia is a complex catabolic state in patients with a malignancy, associated with increased morbidity and mortality. This syndrome is characterized by a redistribution of the body's protein content and a subsequent muscle wasting. The aetiology of this syndrome seems multifactorial, but remains unclear. It is suggested that this catabolic state occurs in response to the alterations in immune interactions between tumor and host. The amino acid arginine and its derivate nitric oxide (NO) play various roles in anti-tumor immune response and the body's homeostasis. Glutamine is the precursor for arginine de novo synthesis and the most abundant amino acid in the body, mainly stored in skeletal muscle. Tumors develop a protection mechanism against the specific anti-tumor attack of the immune system by recruiting myeloid derived suppressor cells (MDSC). The MDSC deplete arginine levels and disturb NO production. We here hypothesize that the perturbation of the arginine/NO metabolism plays a significant role in the aetiology of cancer cachexia. Arginine/ NO metabolism is disturbed in patients with cancer. The body will try to correct this perturbation by mobilizing arginine and glutamine from muscles. The decreased arginine levels and the disturbed NO production activate several cascades, which in turn inhibit protein synthesis and promote proteolysis, leading to cachexia. Cachexia remains one of the most frequent and damaging opportunistic syndromes in cancer patients. In this review we will elaborate on a new hypothesised concept and the underlying mechanisms of this syndrome. New studies are essential to ground this hypothesis and to develop interventions to break through the pathological mechanisms underlying cachexia.

  19. Detection of Pancreatic Cancer-Induced Cachexia Using a Fluorescent Myoblast Reporter System and Analysis of Metabolite Abundance.

    Science.gov (United States)

    Winnard, Paul T; Bharti, Santosh K; Penet, Marie-France; Marik, Radharani; Mironchik, Yelena; Wildes, Flonne; Maitra, Anirban; Bhujwalla, Zaver M

    2016-03-15

    The dire effects of cancer-induced cachexia undermine treatment and contribute to decreased survival rates. Therapeutic options for this syndrome are limited, and therefore efforts to identify signs of precachexia in cancer patients are necessary for early intervention. The applications of molecular and functional imaging that would enable a whole-body "holistic" approach to this problem may lead to new insights and advances for diagnosis and treatment of this syndrome. Here we have developed a myoblast optical reporter system with the purpose of identifying early cachectic events. We generated a myoblast cell line expressing a dual tdTomato:GFP construct that was grafted onto the muscle of mice-bearing human pancreatic cancer xenografts to provide noninvasive live imaging of events associated with cancer-induced cachexia (i.e., weight loss). Real-time optical imaging detected a strong tdTomato fluorescent signal from skeletal muscle grafts in mice with weight losses of only 1.2% to 2.7% and tumor burdens of only approximately 79 to 170 mm(3). Weight loss in cachectic animals was also associated with a depletion of lipid, cholesterol, valine, and alanine levels, which may provide informative biomarkers of cachexia. Taken together, our findings demonstrate the utility of a reporter system that is capable of tracking tumor-induced weight loss, an early marker of cachexia. Future studies incorporating resected tissue from human pancreatic ductal adenocarcinoma into a reporter-carrying mouse may be able to provide a risk assessment of cachexia, with possible implications for therapeutic development. ©2015 American Association for Cancer Research.

  20. The study on mechanism of the modified Chinese herbal compound, jianpijiedu, on a mouse model of hepatic carcinoma cachexia.

    Science.gov (United States)

    Sun, Baoguo; Luo, Haoxuan; Deng, Liuxiang; Zhang, Shijun; Chen, Zexiong

    2016-10-01

    Various studies have investigated hepatic carcinoma cachexia, however, there is little published information regarding the effect of Chinese Medicine carcinoma cachexia. The present study was performed to investigate the effect of modified Chinese herbal compound jianpijiedu (MJPJD) on a mouse model of ascites‑induced hepatic carcinoma cachexia. C57BL/6 mice were randomized to five groups: Control (Group A); xenograft tumor (Group B); low concentration of MJPJD (Group C); high concentration of MJPJD (Group D) and medroxyprogesterone (MPA) combined with indometacin (IND; Group E). The mouse model of ascites‑induced hepatic carcinoma cachexia was established by abdominal injection of H22 hepatic carcinoma cells. Subsequently, the body weight, food intake and gastrocnemius weight were recorded, and the levels of interleukin (IL)‑lα, IL‑6, tumor necrosis factor‑α (TNF‑α) in ascites were detected by enzyme‑linked immunosorbent assay. The protein expression levels of muscle RING‑finger protein‑1 (MU‑RF1) and atrogin 1 were detected by western blotting and immunohistochemistry, and the mRNA levels in gastrocnemius were detected by reverse transcription‑quantitative polymerase chain reaction. Compared with the xenograft tumor group, the administration of MJPJD inhibited the increase in body weight and the volume of ascites, the consumption of gastrocnemius was reduced, the net weight of ascites was maintained, the food intake was enhanced and the levels of the cytokines IL‑lα, IL‑6, TNF‑α in ascites and the levels of MU‑RF1 and atrogin 1 proteins were reduced. These results indicated that MJPJD delays the pathological process of ascites‑induced hepatic carcinoma cachexia, and the mechanism of action may be correlated with a reduction in the levels of IL‑lα, IL‑6, TNF‑α and inhibiting the activation of the ubiquitin proteosome pathway.

  1. Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexia.

    Science.gov (United States)

    Conte, Elena; Camerino, Giulia Maria; Mele, Antonietta; De Bellis, Michela; Pierno, Sabata; Rana, Francesco; Fonzino, Adriano; Caloiero, Roberta; Rizzi, Laura; Bresciani, Elena; Ben Haj Salah, Khoubaib; Fehrentz, Jean-Alain; Martinez, Jean; Giustino, Arcangela; Mariggiò, Maria Addolorata; Coluccia, Mauro; Tricarico, Domenico; Lograno, Marcello Diego; De Luca, Annamaria; Torsello, Antonio; Conte, Diana; Liantonio, Antonella

    2017-06-01

    Cachexia is a wasting condition associated with cancer types and, at the same time, is a serious and dose-limiting side effect of cancer chemotherapy. Skeletal muscle loss is one of the main characteristics of cachexia that significantly contributes to the functional muscle impairment. Calcium-dependent signaling pathways are believed to play an important role in skeletal muscle decline observed in cachexia, but whether intracellular calcium homeostasis is affected in this situation remains uncertain. Growth hormone secretagogues (GHS), a family of synthetic agonists of ghrelin receptor (GHS-R1a), are being developed as a therapeutic option for cancer cachexia syndrome; however, the exact mechanism by which GHS interfere with skeletal muscle is not fully understood. By a multidisciplinary approach ranging from cytofluorometry and electrophysiology to gene expression and histology, we characterized the calcium homeostasis in fast-twitch extensor digitorum longus (EDL) muscle of adult rats with cisplatin-induced cachexia and established the potential beneficial effects of two GHS (hexarelin and JMV2894) at this level. Additionally, in vivo measures of grip strength and of ultrasonography recordings allowed us to evaluate the functional impact of GHS therapeutic intervention. Cisplatin-treated EDL muscle fibres were characterized by a ~18% significant reduction of the muscle weight and fibre diameter together with an up-regulation of atrogin1/Murf-1 genes and a down-regulation of Pgc1-a gene, all indexes of muscle atrophy, and by a two-fold increase in resting intracellular calcium, [Ca2+ ]i , compared with control rats. Moreover, the amplitude of the calcium transient induced by caffeine or depolarizing high potassium solution as well as the store-operated calcium entry were ~50% significantly reduced in cisplatin-treated rats. Calcium homeostasis dysregulation parallels with changes of functional ex vivo (excitability and resting macroscopic conductance) and in vivo

  2. Reversal of muscle atrophy by Zhimu and Huangbai herb pair via activation of IGF-1/Akt and autophagy signal in cancer cachexia.

    Science.gov (United States)

    Zhuang, Pengwei; Zhang, Jinbao; Wang, Yan; Zhang, Mixia; Song, Lili; Lu, Zhiqiang; Zhang, Lu; Zhang, Fengqi; Wang, Jing; Zhang, Yanjun; Wei, Hongjun; Li, Hongyan

    2016-03-01

    Muscle atrophy is the prominent clinical feature of cancer-induced cachexia. Zhimu and Huangbai herb pair (ZBHP) has been used since ancient China times and have been phytochemically investigated for constituents that might cause anti-cancer, diabetes, and their complication. In this study, the effects and mechanisms of ZBHP on reversal of muscle atrophy were explored. C57BL/6 mice implanted with colon-26 adenocarcinoma were chosen to develop cancer cachexia for evaluating the effects of ZBHP on reversal of muscle atrophy. The body weight, survival time, inflammatory cytokines, and pathological changes of muscle were monitored. In addition, IGF-1/Akt and autophagy pathway members were analyzed to interpret the mechanism of drug response. The function and morphology of skeletal muscle in cachexia model were significantly disturbed, and the survival time was shortened. Consistently, inflammatory cytokines and muscle atrophy-related atrogin-1, MuRF1, and FOXO3 were significantly increased, and IGF-1/Akt and autophagy signal pathways were depressed. Treatment with ZBHP significantly alleviated tumor-free body weight reduction and cachexia-induced changes in cytokines and prolonged survival. ZBHP treatment not only inhibited the muscle atrophy-related genes but also activated the IGF-1/Akt and autophagy signal pathways to facilitate the protein synthesis. The results revealed that ZBHP treatment could inhibit the muscle atrophy induced by cancer cachexia and prolong the survival time, and ZBHP may be of value as a pharmacological alternative in treatment of cancer cachexia.

  3. Cancer cachexia and its impact on patient dignity: What nurses need to know

    Directory of Open Access Journals (Sweden)

    Susan McClement

    2016-01-01

    Full Text Available Noted physician, Sr. William Osler, is credited with saying, “Care more particularly for the individual patient than for the special features of the disease”. Osler understood that each patient for whom we care is first and foremost a person, who also happens to be living with a particular illness. In addition to understanding the nature of the patient's illness, therefore, it is also critically important that we come to understand the patient's unique story and set of circumstances. Doing so allows us to engage with patients in a way that affirms their sense of dignity and personhood. Drawing on the exemplar of cancer cachexia, this editorial reminds clinicians of the importance of Osler's sage advice to attend to patient dignity and personhood, and provides nurses with direction about how they can do that in practice.

  4. ActRII blockade protects mice from cancer cachexia and prolongs survival in the presence of anti-cancer treatments.

    Science.gov (United States)

    Hatakeyama, Shinji; Summermatter, Serge; Jourdain, Marie; Melly, Stefan; Minetti, Giulia C; Lach-Trifilieff, Estelle

    2016-01-01

    Cachexia affects the majority of patients with advanced cancer and is associated with reduced treatment tolerance, response to therapy, quality of life, and life expectancy. Cachectic patients with advanced cancer often receive anti-cancer therapies against their specific cancer type as a standard of care, and whether specific ActRII inhibition is efficacious when combined with anti-cancer agents has not been elucidated yet. In this study, we evaluated interactions between ActRII blockade and anti-cancer agents in CT-26 mouse colon cancer-induced cachexia model. CDD866 (murinized version of bimagrumab) is a neutralizing antibody against the activin receptor type II (ActRII) preventing binding of ligands such as myostatin and activin A, which are involved in cancer cachexia. CDD866 was evaluated in association with cisplatin as a standard cytotoxic agent or with everolimus, a molecular-targeted agent against mammalian target of rapamycin (mTOR). In the early studies, the treatment effect on cachexia was investigated, and in the additional studies, the treatment effect on progression of cancer and the associated cachexia was evaluated using body weight loss or tumor volume as interruption criteria. Cisplatin accelerated body weight loss and tended to exacerbate skeletal muscle loss in cachectic animals, likely due to some toxicity of this anti-cancer agent. Administration of CDD866 alone or in combination with cisplatin protected from skeletal muscle weight loss compared to animals receiving only cisplatin, corroborating that ActRII inhibition remains fully efficacious under cisplatin treatment. In contrast, everolimus treatment alone significantly protected the tumor-bearing mice against skeletal muscle weight loss caused by CT-26 tumor. CDD866 not only remains efficacious in the presence of everolimus but also showed a non-significant trend for an additive effect on reversing skeletal muscle weight loss. Importantly, both combination therapies slowed down time

  5. Pulmonary cachexia

    National Research Council Canada - National Science Library

    Schols, Annemie M.W.J

    2002-01-01

    ... indeed found that body weight might be a discriminating factor. This led to the classical description of the pink puffer (emphysematous type) and the blue bloater (bronchitic type). Initially weight loss was thought to be an epiphenomenonon of severe disease and an adaptive mechanism to decrease oxygen consumption. Potential adverse effect...

  6. Oral Treatment with the Ghrelin Receptor Agonist HM01 Attenuates Cachexia in Mice Bearing Colon-26 (C26) Tumors

    OpenAIRE

    Villars, Fabienne O.; Pietra, Claudio; Giuliano, Claudio; Lutz, Thomas A.; Riediger, Thomas

    2017-01-01

    The gastrointestinal hormone ghrelin reduces energy expenditure and stimulates food intake. Ghrelin analogs are a possible treatment against cancer anorexia-cachexia syndrome (CACS). This study aimed to investigate whether oral treatment with the non-peptidergic ghrelin receptor agonist HM01 counteracts CACS in colon-26 (C26) tumor-bearing mice. The C26 tumor model is characterized by pronounced body weight (BW) loss and muscle wasting in the absence of severe anorexia. We analyzed the time c...

  7. A predictive model of inflammatory markers and patient-reported symptoms for cachexia in newly diagnosed pancreatic cancer patients.

    Science.gov (United States)

    Fogelman, David R; Morris, J; Xiao, L; Hassan, M; Vadhan, S; Overman, M; Javle, S; Shroff, R; Varadhachary, G; Wolff, R; Vence, L; Maitra, A; Cleeland, C; Wang, X S

    2017-06-01

    Cachexia is a frequent manifestation of pancreatic cancer, can limit a patient's ability to take chemotherapy, and is associated with shortened survival. We developed a model to predict the early onset of cachexia in advanced pancreatic cancer patients. Patients with newly diagnosed, untreated metastatic or locally advanced pancreatic cancer were included. Serum cytokines were drawn prior to therapy. Patient symptoms were recorded using the M.D. Anderson Symptom Inventory (MDASI). Our primary endpoint was either 10% weight loss or death within 60 days of the start of therapy. Twenty-seven of 89 patients met the primary endpoint (either having lost 10% of body weight or having died within 60 days of the start of treatment). In a univariate analysis, smoking, history symptoms of pain and difficulty swallowing, high levels of MK, CXCL-16, IL-6, TNF-a, and low IL-1b all correlated with this endpoint. We used recursive partition to fit a regression tree model, selecting four of 26 variables (CXCL-16, IL-1b, pain, swallowing difficulty) as important in predicting cachexia. From these, a model of two cytokines (CXCL-16 > 5.135 ng/ml and IL-1b Cachexia is frequent in pancreatic cancer; one in three patients met our endpoint of 10% weight loss or death within 60 days. Inflammatory cytokines are better than conventional tumor markers at predicting this outcome. Recursive partitioning analysis suggests that a model of CXCL-16 and IL-1B may offer a better ability than individual cytokines to predict this outcome.

  8. Depletion of white adipose tissue in cancer cachexia syndrome is associated with inflammatory signaling and disrupted circadian regulation.

    Directory of Open Access Journals (Sweden)

    Maria Tsoli

    Full Text Available Involuntary weight loss in patients with cancer is the hallmark of cancer cachexia. The etiology of cachexia is multifactorial involving loss of skeletal muscle and adipose tissue associated with high systemic levels of acute phase proteins and inflammatory cytokines. While muscle wasting overtly impacts on cancer patient quality of life, loss of lipid depots represents a sustained energy imbalance. In this study fat depletion was examined in Colon-26 model of cancer cachexia, which is a widely used rodent model of this syndrome. We investigated diurnal expression of circadian rhythm regulators as well as key mediators of energy metabolism and cytokine signaling. Mice bearing the C26 tumour exhibited reduced adipose mass, elevated adipose tissue lipolysis and a 5-fold increase in plasma levels of free fatty acids. These changes were associated with activated IL-6 signaling in WAT through a 3-fold increase in phosphorylated STAT3 and high SOCS3 gene expression levels. In addition perturbations in circadian regulation of lipid metabolism were also observed. Lipid catabolism did not appear to be influenced by the classical PKA pathway activating the lipase HSL. ATGL protein levels were elevated 2-fold in cachectic mice while 4-fold increase phosphorylated ACC and a 2-fold decrease in phosphorylated 4EBP1 was observed indicating that lipid metabolism is modulated by the ATGL & AMPK/mTOR pathways. This study provides evidence for activation of cytokine signaling and concomitant alterations in circadian rhythm and regulators of lipid metabolism in WAT of cachectic animals.

  9. Depletion of White Adipose Tissue in Cancer Cachexia Syndrome Is Associated with Inflammatory Signaling and Disrupted Circadian Regulation

    Science.gov (United States)

    Tsoli, Maria; Schweiger, Martina; Vanniasinghe, Anne S.; Painter, Arran; Zechner, Rudolf; Clarke, Stephen; Robertson, Graham

    2014-01-01

    Involuntary weight loss in patients with cancer is the hallmark of cancer cachexia. The etiology of cachexia is multifactorial involving loss of skeletal muscle and adipose tissue associated with high systemic levels of acute phase proteins and inflammatory cytokines. While muscle wasting overtly impacts on cancer patient quality of life, loss of lipid depots represents a sustained energy imbalance. In this study fat depletion was examined in Colon-26 model of cancer cachexia, which is a widely used rodent model of this syndrome. We investigated diurnal expression of circadian rhythm regulators as well as key mediators of energy metabolism and cytokine signaling. Mice bearing the C26 tumour exhibited reduced adipose mass, elevated adipose tissue lipolysis and a 5-fold increase in plasma levels of free fatty acids. These changes were associated with activated IL-6 signaling in WAT through a 3-fold increase in phosphorylated STAT3 and high SOCS3 gene expression levels. In addition perturbations in circadian regulation of lipid metabolism were also observed. Lipid catabolism did not appear to be influenced by the classical PKA pathway activating the lipase HSL. ATGL protein levels were elevated 2-fold in cachectic mice while 4-fold increase phosphorylated ACC and a 2-fold decrease in phosphorylated 4EBP1 was observed indicating that lipid metabolism is modulated by the ATGL & AMPK/mTOR pathways. This study provides evidence for activation of cytokine signaling and concomitant alterations in circadian rhythm and regulators of lipid metabolism in WAT of cachectic animals. PMID:24667661

  10. Syngeneic B16F10 Melanoma Causes Cachexia and Impaired Skeletal Muscle Strength and Locomotor Activity in Mice

    Directory of Open Access Journals (Sweden)

    Fabrício A. Voltarelli

    2017-09-01

    Full Text Available Muscle wasting has been emerging as one of the principal components of cancer cachexia, leading to progressive impairment of work capacity. Despite early stages melanomas rarely promotes weight loss, the appearance of metastatic and/or solid tumor melanoma can leads to cachexia development. Here, we investigated the B16F10 tumor-induced cachexia and its contribution to muscle strength and locomotor-like activity impairment. C57BL/6 mice were subcutaneously injected with 5 × 104 B16F10 melanoma cells or PBS as a Sham negative control. Tumor growth was monitored during a period of 28 days. Compared to Sham mice, tumor group depicts a loss of skeletal muscle, as well as significantly reduced muscle grip strength and epididymal fat mass. This data are in agreement with mild to severe catabolic host response promoted by elevated serum tumor necrosis factor-alpha (TNF-α, interleukin-6 (IL-6 and lactate dehydrogenase (LDH activity. Tumor implantation has also compromised general locomotor activity and decreased exploratory behavior. Likewise, muscle loss, and elevated inflammatory interleukin were associated to muscle strength loss and locomotor activity impairment. In conclusion, our data demonstrated that subcutaneous B16F10 melanoma tumor-driven catabolic state in response to a pro-inflammatory environment that is associated with impaired skeletal muscle strength and decreased locomotor activity in tumor-bearing mice.

  11. [Anorexia-cachexia frequency and its gastrointestinal symptoms association in paliative patients at the Instituto Nacional de Cancerología, México].

    Science.gov (United States)

    Pérez Camargo, Dana Aline; Allende Pérez, Silvia R; Meneses García, Abelardo; De Nicola Delfin, Luigina; Copca Mendoza, Erika Thalía; Sánchez López, Miriam S; Flores García, Martha Karen; Verástegui Avilés, Emma

    2014-10-01

    Anorexia-cachexia is a frequent syndrome among cancer patients, specially in late stages: the global prevalence of para-neoplastic anorexia-cachexia ranges between 20-40% in the diagnostic stage and between 70-80% in the late stage of the disease. The co-existence of functional or structural digestive abnormalities is frequently observed among cancer patients; this is a consequence of the tumor growth and of those systemic phenomena related to metabolism, which are affected by the relationship tumor-host specific to anorexia- cachexia. This study aimed at establishing the frequency of anorexia-cachexia, as well as its relationship to GI symptoms in the context of palliative care patients at the Instituto Nacional de Cancerología, México City. Analytic cross-sectional study including 100 patients diagnosed with late-stage cancer, age range 18-80, and a Karnofsky score > 50, as well as an ECOG anorexia-cachexia, and 39% (n=39)did not. 56% of the sample participants (n=34) were women, and 44% (n=27) were men. GI symptoms associated with anorexia-cachexia were: nausea (p= 0.0001), vomiting (p=0.004), early satiety (p=0.0005), dysgeusia(p=0.0005) and dysphagia (p=0.001). Anorexia and cachexia are among the most devastating and frequent symptoms in late-stage cancer patients and they are also associated with GI symptoms affecting the physical, psychosocial and existential aspects of the patient's life. Data from this research validate the importance of an early nutrition support in palliative patients so that they can achieve a better quality of life. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  12. STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

    Science.gov (United States)

    Kunzevitzky, Noelia; Guttridge, Denis C.; Khuri, Sawsan; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2011-01-01

    Background Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26)-carcinoma cachexia. Methodology/Principal Findings Moderate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer. Conclusions/Significance These results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and translated in muscle such

  13. Eicosapentaenoic acid and oxypurinol in the treatment of muscle wasting in a mouse model of cancer cachexia.

    Directory of Open Access Journals (Sweden)

    Vanessa C Vaughan

    Full Text Available Cancer cachexia is a wasting condition, driven by systemic inflammation and oxidative stress. This study investigated eicosapentaenoic acid (EPA in combination with oxypurinol as a treatment in a mouse model of cancer cachexia. Mice with cancer cachexia were randomized into 4 treatment groups (EPA (0.4 g/kg/day, oxypurinol (1 mmol/L ad-lib, combination, or control, and euthanized after 29 days. Analysis of oxidative damage to DNA, mRNA analysis of pro-oxidant, antioxidant and proteolytic pathway components, along with enzyme activity of pro- and antioxidants were completed on gastrocnemius muscle. The control group displayed earlier onset of tumor compared to EPA and oxypurinol groups (P<0.001. The EPA group maintained body weight for an extended duration (20 days compared to the oxypurinol (5 days and combination (8 days groups (P<0.05. EPA (18.2±3.2 pg/ml and combination (18.4±3.7 pg/ml groups had significantly higher 8-OH-dG levels than the control group (12.9±1.4 pg/ml, P≤0.05 indicating increased oxidative damage to DNA. mRNA levels of GPx1, MURF1 and MAFbx were higher following EPA treatment compared to control (P≤0.05. Whereas oxypurinol was associated with higher GPx1, MnSOD, CAT, XDH, MURF1, MAFbx and UbB mRNA compared to control (P≤0.05. Activity of total SOD was higher in the oxypurinol group (32.2±1.5 U/ml compared to control (27.0±1.3 U/ml, P<0.01, GPx activity was lower in the EPA group (8.76±2.0 U/ml compared to control (14.0±1.9 U/ml, P<0.05, and catalase activity was lower in the combination group (14.4±2.8 U/ml compared to control (20.9±2.0 U/ml, P<0.01. There was no change in XO activity. The increased rate of weight decline in mice treated with oxypurinol indicates that XO may play a protective role during the progression of cancer cachexia, and its inhibition is detrimental to outcomes. In combination with EPA, there was little significant improvement from control, indicating oxypurinol is unlikely to be a

  14. Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour‐bearing mice

    Science.gov (United States)

    Brown, Jacob L.; Rosa‐Caldwell, Megan E.; Lee, David E.; Blackwell, Thomas A.; Brown, Lemuel A.; Perry, Richard A.; Haynie, Wesley S.; Hardee, Justin P.; Carson, James A.; Wiggs, Michael P.; Washington, Tyrone A.

    2017-01-01

    Abstract Background Cancer cachexia is largely irreversible, at least via nutritional means, and responsible for 20–40% of cancer‐related deaths. Therefore, preventive measures are of primary importance; however, little is known about muscle perturbations prior to onset of cachexia. Cancer cachexia is associated with mitochondrial degeneration; yet, it remains to be determined if mitochondrial degeneration precedes muscle wasting in cancer cachexia. Therefore, our purpose was to determine if mitochondrial degeneration precedes cancer‐induced muscle wasting in tumour‐bearing mice. Methods First, weight‐stable (MinStable) and cachectic (MinCC) Apc Min/+ mice were compared with C57Bl6/J controls for mRNA contents of mitochondrial quality regulators in quadriceps muscle. Next, Lewis lung carcinoma (LLC) cells or PBS (control) were injected into the hind flank of C57Bl6/J mice at 8 week age, and tumour allowed to develop for 1, 2, 3, or 4 weeks to examine time course of cachectic development. Succinate dehydrogenase stain was used to measure oxidative phenotype in tibialis anterior muscle. Mitochondrial quality and function were assessed using the reporter MitoTimer by transfection to flexor digitorum brevis and mitochondrial function/ROS emission in permeabilized adult myofibres from plantaris. RT‐qPCR and immunoblot measured the expression of mitochondrial quality control and antioxidant proteins. Data were analysed by one‐way ANOVA with Student–Newman–Kuels post hoc test. Results MinStable mice displayed ~50% lower Pgc‐1α, Pparα, and Mfn2 compared with C57Bl6/J controls, whereas MinCC exhibited 10‐fold greater Bnip3 content compared with C57Bl6/J controls. In LLC, cachectic muscle loss was evident only at 4 weeks post‐tumour implantation. Oxidative capacity and mitochondrial content decreased by ~40% 4 weeks post‐tumour implantation. Mitochondrial function decreased by ~25% by 3 weeks after tumour implantation. Mitochondrial

  15. A New Transgenic Mouse Model of Heart Failure and Cardiac Cachexia Raised by Sustained Activation of Met Tyrosine Kinase in the Heart

    Directory of Open Access Journals (Sweden)

    Valentina Sala

    2016-01-01

    Full Text Available Among other diseases characterized by the onset of cachexia, congestive heart failure takes a place of relevance, considering the high prevalence of this pathology in most European countries and in the United States, and is undergoing a rapid increase in developing countries. Actually, only few models of cardiac cachexia exist. Difficulties in the recruitment and follow-up of clinical trials implicate that new reproducible and well-characterized animal models are pivotal in developing therapeutic strategies for cachexia. We generated a new model of cardiac cachexia: a transgenic mouse expressing Tpr-Met receptor, the activated form of c-Met receptor of hepatocyte growth factor, specifically in the heart. We showed that the cardiac-specific induction of Tpr-Met raises a cardiac hypertrophic remodelling, which progresses into concentric hypertrophy with concomitant increase in Gdf15 mRNA levels. Hypertrophy progresses to congestive heart failure with preserved ejection fraction, characterized by reduced body weight gain and food intake and skeletal muscle wasting. Prevention trial by suppressing Tpr-Met showed that loss of body weight could be prevented. Skeletal muscle wasting was also associated with altered gene expression profiling. We propose transgenic Tpr-Met mice as a new model of cardiac cachexia, which will constitute a powerful tool to understand such complex pathology and test new drugs/approaches at the preclinical level.

  16. Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia--can findings from animal models be translated to humans?

    Science.gov (United States)

    Mueller, Tara C; Bachmann, Jeannine; Prokopchuk, Olga; Friess, Helmut; Martignoni, Marc E

    2016-02-08

    Cachexia is a multi-factorial, systemic syndrome that especially affects patients with cancer of the gastrointestinal tract, and leads to reduced treatment response, survival and quality of life. The most important clinical feature of cachexia is the excessive wasting of skeletal muscle mass. Currently, an effective treatment is still lacking and the search for therapeutic targets continues. Even though a substantial number of animal studies have contributed to a better understanding of the underlying mechanisms of the loss of skeletal muscle mass, subsequent clinical trials of potential new drugs have not yet yielded any effective treatment for cancer cachexia. Therefore, we questioned to which degree findings from animal studies can be translated to humans in clinical practice and research. A substantial amount of animal studies on the molecular mechanisms of muscle wasting in cancer cachexia has been conducted in recent years. This extensive review of the literature showed that most of their observations could not be consistently reproduced in studies on human skeletal muscle samples. However, studies on human material are scarce and limited in patient numbers and homogeneity. Therefore, their results have to be interpreted critically. More research is needed on human tissue samples to clarify the signaling pathways that lead to skeletal muscle loss, and to confirm pre-selected drug targets from animal models in clinical trials. In addition, improved diagnostic tools and standardized clinical criteria for cancer cachexia are needed to conduct standardized, randomized controlled trials of potential drug candidates in the future.

  17. A New Transgenic Mouse Model of Heart Failure and Cardiac Cachexia Raised by Sustained Activation of Met Tyrosine Kinase in the Heart.

    Science.gov (United States)

    Sala, Valentina; Gatti, Stefano; Gallo, Simona; Medico, Enzo; Cantarella, Daniela; Cimino, James; Ponzetto, Antonio; Crepaldi, Tiziana

    2016-01-01

    Among other diseases characterized by the onset of cachexia, congestive heart failure takes a place of relevance, considering the high prevalence of this pathology in most European countries and in the United States, and is undergoing a rapid increase in developing countries. Actually, only few models of cardiac cachexia exist. Difficulties in the recruitment and follow-up of clinical trials implicate that new reproducible and well-characterized animal models are pivotal in developing therapeutic strategies for cachexia. We generated a new model of cardiac cachexia: a transgenic mouse expressing Tpr-Met receptor, the activated form of c-Met receptor of hepatocyte growth factor, specifically in the heart. We showed that the cardiac-specific induction of Tpr-Met raises a cardiac hypertrophic remodelling, which progresses into concentric hypertrophy with concomitant increase in Gdf15 mRNA levels. Hypertrophy progresses to congestive heart failure with preserved ejection fraction, characterized by reduced body weight gain and food intake and skeletal muscle wasting. Prevention trial by suppressing Tpr-Met showed that loss of body weight could be prevented. Skeletal muscle wasting was also associated with altered gene expression profiling. We propose transgenic Tpr-Met mice as a new model of cardiac cachexia, which will constitute a powerful tool to understand such complex pathology and test new drugs/approaches at the preclinical level.

  18. Psychosocial issues in the diagnosis and management of cancer cachexia and anorexia.

    Science.gov (United States)

    Lesko, L M

    1989-01-01

    Anorexia with its associated decreased food intake and weight loss is a common and profoundly important symptom in cancer, and one which has at times a psychological as well as physical component. When it is physical in origin it may be caused directly or indirectly by the disease process or treatment. Most poorly understood is the anorexia-cachexia syndrome of advanced disease. Psychological causes often reflect anxiety about cancer, its possible progression, depression, anticipatory phenomena, and learned food adversions. Pre-existing psychiatric disorders, especially anorexia nervosa or paranoid states, can substantially complicate cancer treatment. Learned food aversions, which can further restrict limited intake, have been demonstrated in children receiving chemotherapy and may also contribute to aversions of specific foods seen among adult patients after chemotherapy or radiation. Regardless of etiology, psychological management of the anorexia is often helpful. Optimal management often involves use of a combination of modalities: psychotherapeutic, behavioral and/or pharmacologic supplemented by education, counseling and support. Behavioral techniques such as relaxation exercises are useful tools to alter this response as well as to relieve the anxiety precipitated by the patient's concerns about anorexia and weight loss. Environmental interventions and nutritional advice can also be of considerable value in reversing the negative effects of this distressing symptom in cancer.

  19. Components of the anorexia-cachexia syndrome: gastrointestinal symptom correlates of cancer anorexia.

    Science.gov (United States)

    Yavuzsen, Tugba; Walsh, Declan; Davis, Mellar P; Kirkova, Jordanka; Jin, Tao; LeGrand, Susan; Lagman, Ruth; Bicanovsky, Lesley; Estfan, Bassam; Cheema, Bushra; Haddad, Abdo

    2009-12-01

    Cancer-related anorexia is traditionally considered part of a complex but ill-defined anorexia-cachexia syndrome in which anorexia is intimately associated with other gastrointestinal (GI) symptoms and weight loss. We surveyed cancer patients with anorexia to learn more about the relationship between anorexia and these symptoms. A 22-item GI questionnaire assessed the severity of anorexia and the prevalence of concurrent GI symptoms, including taste changes, food aversions, altered sense of smell, and diurnal food intake changes. The relationship between anorexia severity and anticancer therapy and prior menstrual or pregnancy-related appetite changes was also assessed. Ninety-five of 101 patients with anorexia surveyed had complete data. Seventy-eight percent of them had moderate or severe anorexia. Abnormal diurnal appetite variation, taste changes, and food aversions were present in over 50% of all those with anorexia. Judged by the numerical rating scale, the worse the anorexia, the more prevalent were early satiety, constipation, vomiting, and food aversions. Those with more severe anorexia had greater weight loss, and worse performance status. Anorexia severity did not correlate with that during prior menses/pregnancy or antitumor therapy. Evaluation of multiple other GI symptoms is important in understanding the total experience of cancer anorexia. Early satiety, taste changes, food aversions, and altered sense of smell are important accompanying GI symptoms. Most validated anorexia tools do not assess these commonly associated GI symptoms. Future research should develop a comprehensive anorexia symptom questionnaire.

  20. Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact.

    Science.gov (United States)

    Prado, C M; Cushen, S J; Orsso, C E; Ryan, A M

    2016-05-01

    Our understanding of body composition (BC) variability in contemporary populations has significantly increased with the use of imaging techniques. Abnormal BC such as sarcopenia (low muscle mass) and obesity (excess adipose tissue) are predictors of poorer prognosis in a variety of conditions or clinical situations. As a catabolic illness, a defining feature of cancer is muscle loss. Although the conceptual model of wasting in cancer is typically conceived as involuntary weight loss leading to low body weight, recent studies have shown that both sarcopenia and cachexia can be present with obesity. The combination of low muscle and high adipose tissue (sarcopenic obesity) is an emerging abnormal BC phenotype prevalent across the body weight, and hence BMI spectra. Sarcopenia and sarcopenic obesity in cancer are in most instances occult conditions, which have been independently associated with higher incidence of chemotherapy toxicity, shorter time to tumour progression, poorer outcomes of surgery, physical impairment and shorter survival. Although the mechanisms are yet to be fully understood, the associations with poorer clinical outcomes emphasise the value of nutritional assessment as well as the need to develop appropriate interventions to countermeasure abnormal BC. Sarcopenia and sarcopenic obesity create diverse nutritional requirements, highlighting the compelling need for a more comprehensive and differentiated understanding of energy and protein requirements in this heterogeneous population.

  1. Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC.

    Science.gov (United States)

    Zhang, Hongjie; Garcia, Jose M

    2015-06-01

    Cancer anorexia-cachexia syndrome (CACS) is associated with increased morbidity and mortality. Anamorelin is a novel, orally active ghrelin receptor agonist in clinical development for the treatment of CACS in NSCLC. The aim of this review is to summarize preclinical and clinical studies evaluating anamorelin as a potential promising treatment for CACS in NSCLC. Pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability of anamorelin for the treatment of CACS in NSCLC were reviewed. Anamorelin administration may lead to increases in food intake, body weight and lean body mass, and a stimulatory effect on growth hormone secretion in NSCLC patients. Anamorelin is well tolerated with no dose-limiting toxicities identified to date. Targeting ghrelin receptors presents the advantage of potentially addressing multiple mechanisms of CACS simultaneously including appetite, muscle protein balance, adipose tissue metabolism, energy expenditure and inflammation. Clinical data suggest that anamorelin is well tolerated and it effectively increases appetite, body weight and lean mass in patients with advanced NSCLC. Long-term safety remains unknown at this time. The potential synergistic effects of anamorelin with nutritional support or exercise as well as its efficacy/safety in other tumor types are also unknown.

  2. Sytemic inflammation in cachexia - is tumour cytokine expression profile the culprit?

    Directory of Open Access Journals (Sweden)

    Emidio Marques De Matos-Neto

    2015-12-01

    Full Text Available Cachexia affects about 80 percent of gastrointestinal cancer patients. This multifactorial syndrome resulting in involuntary and continuous weight loss is accompanied by systemic inflammation and immune cell infiltration in various tissues. Understanding the interactions between tumor, immune cells and peripheral tissues could help attenuating systemic inflammation. Therefore, we investigated inflammation in the subcutaneous adipose tissue and in the tumor, in weight stable and cachectic cancer patients with same diagnosis, in order to establish correlations between tumor microenvironment and secretory pattern with adipose tissue and systemic inflammation. Infiltrating monocyte phenotypes of subcutaneous and tumor vascular-stromal fraction were identified by flow cytometry. Gene and protein expression of inflammatory and chemotactic factors was measured with qRT-PCR and Multiplex Magpix® system, respectively. Subcutaneous vascular-stromal fraction exhibited no differences in regard to macrophage subtypes, while in the tumor, the percentage of M2 macrophages was decreased in the cachectic patients, in comparison to weight-stable counterparts. CCL3, CCL4 and IL-1β expression was higher in the adipose tissue and tumor tissue in cachectic group. In both tissues chemotactic factors were positively correlated with IL-1β. Furthermore, positive correlations were found for the content of chemoattractants and cytokines in the tumor and adipose tissue. The results strongly suggest that the crosstalk between the tumor and peripheral tissues is more pronounced in cachectic patients, compared to weight-stable patients with the same tumor diagnosis.

  3. 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).

    Science.gov (United States)

    LeBlanc, Thomas W; Samsa, Greg P; Wolf, Steven P; Locke, Susan C; Cella, David F; Abernethy, Amy P

    2015-08-01

    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. We tested the performance of the FAACT and its anorexia-cachexia subscale (ACS) within a dataset of patients with advanced non-small cell lung cancer (aNSCLC), using standard statistical methods. We then compared the performance of commonly used QoL measures stratified by CACS status and by patient self-report of appetite and weight loss. The FAACT and its ACS demonstrate internal validity consistent with acceptable published ranges for other QoL scales (Cronbach alpha = 0.9 and 0.79, respectively). Correlation coefficients demonstrate moderate correlations in the expected directions between FAACT and ACS and scales that measure related constructs. Comparing patients with and without CACS, the ACS is more sensitive to change than other QoL instruments (mean score 33.1 vs. 37.2, p = 0.011, ES = 0.58). In patients with aNSCLC, the FAACT and its ACS performed well compared with other instruments, further supporting their validity and value in clinical research. FAACT and ACS scores covaried with symptoms and other QoL changes that are typical hallmarks of CACS, lending further support to their use as QoL endpoints in clinical trials among patients with CACS.

  4. The role of physical activity in counteracting age-related sarcopenia and cancer cachexia: A brief literature review

    Directory of Open Access Journals (Sweden)

    Scalabrin Mattia

    2016-01-01

    Full Text Available Muscle tissue plays several important health functions . In addition to the important mechanical functions, it represents the biggest reserve of body proteins and it is also able to produce several myokines that are able to induce important beneficial effects, through the interaction with different organs. The loss of muscle mass has a tremendous impact on health and it is not surprising that a great interest has raised on two degenerative, irreversible and unstoppable conditions known as sarcopenia and cachexia. Sarcopenia, the age-related loss of muscle mass, is not a disease or a syndrome, it is not even a medical sign sometimes. Indeed, a general consensus among scientists does not exist regarding the definition and the identification criteria of this condition. On the other hand, cachexia is a wasting syndrome characterized by an uncontrolled and unstoppable loss of muscle mass, associated with fatigue and weakness. It is often associated with a disease like cancer, AIDS, Chronic Obstructive Pulmonary Disease (COPD, multiple sclerosis, tuberculosis etc. Given the complexity of these muscle conditions and considering that during aging and cancer there is an increased risk of comorbidities, regular physical activity might be a crucial point to be carefully evaluated on a single patient basis. The aim of this review is to highlight the impact on society and the etiology of sarcopenia and cancer cachexia, with particular regard to the role played by physical activity in preventing and counteracting these muscle-wasting conditions, focusing attention also on the limitation factors that must be considered during the prescription of physical activity to sarcopenic and cachectic patients.

  5. Health-Related Quality of Life, Cachexia and Overall Survival After Major Upper Abdominal Surgery: A Prospective Cohort Study.

    Science.gov (United States)

    Aahlin, E K; Tranø, G; Johns, N; Horn, A; Søreide, J A; Fearon, K C; Revhaug, A; Lassen, K

    2017-03-01

    Major upper abdominal surgery is often associated with reduced health-related quality of life and reduced survival. Patients with upper abdominal malignancies often suffer from cachexia, represented by preoperative weight loss and sarcopenia (low skeletal muscle mass) and this might affect both health-related quality of life and survival. We aimed to investigate how health-related quality of life is affected by cachexia and how health-related quality of life relates to long-term survival after major upper abdominal surgery. From 2001 to 2006, 447 patients were included in a Norwegian multicenter randomized controlled trial in major upper abdominal surgery. In this study, six years later, these patients were analyzed as a single prospective cohort and survival data were retrieved from the National Population Registry. Cachexia was derived from patient-reported preoperative weight loss and sarcopenia as assessed from computed tomography images taken within three months preoperatively. In the original trial, self-reported health-related quality of life was assessed preoperatively at trial enrollment and eight weeks postoperatively with the health-related quality of life questionnaire Short Form 36. A majority of the patients experienced improved mental health-related quality of life and, to a lesser extent, deteriorated physical health-related quality of life following surgery. There was a significant association between preoperative weight loss and reduced physical health-related quality of life. No association between sarcopenia and health-related quality of life was observed. Overall survival was significantly associated with physical health-related quality of life both pre- and postoperatively, and with postoperative mental health-related quality of life. The association between health-related quality of life and survival was particularly strong for postoperative physical health-related quality of life. Postoperative physical health-related quality of life

  6. Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype.

    Science.gov (United States)

    Chacon-Cabrera, Alba; Mateu-Jimenez, Mercè; Langohr, Klaus; Fermoselle, Clara; García-Arumí, Elena; Andreu, Antoni L; Yelamos, Jose; Barreiro, Esther

    2017-12-01

    Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1-/- ) and Parp-2-/- mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1-/- , and Parp-2-/- ), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-κB signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1-/- and Parp-2-/- cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-κB signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention. © 2017 Wiley Periodicals, Inc.

  7. Dual Inhibition of MEK and PI3K/Akt Rescues Cancer Cachexia through Both Tumor Extrinsic and Intrinsic Activities

    Science.gov (United States)

    Mace, Thomas A.; Farren, Matthew R.; Farris, Alton B.; Young, Gregory S.; Elnaggar, Omar; Che, Zheng; Timmers, Cynthia D.; Rajasekera, Priyani; Maskarinec, Jennifer M.; Bloomston, Mark; Bekaii-Saab, Tanios; Guttridge, Denis C.; Lesinski, Gregory B.

    2016-01-01

    Involuntary weight loss, a part of the cachexia syndrome, is a debilitating co-morbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses, but surprisingly gained weight and increased their skeletal muscle mass. This implied that MEK inhibition might be anti-cachectic. To test this potential effect of MEK inhibition, we utilized the established Colon-26 model of cancer cachexia and the MEK1/2 inhibitor MEK162. Results showed that MEK inhibition effectively prevented muscle wasting. Importantly, MEK162 retained its ability to spare muscle loss even in mice bearing a Colon-26 clone resistant to the MEK inhibitor, demonstrating that the effects of blocking MEK is at least in part independent of the tumor. Because single agent MEK inhibitors have been limited as a front-line targeted therapy due to compensatory activation of other oncogenic signaling pathways, we combined MEK162 with the PI3K/Akt inhibitor buparlisib. Results showed that this combinatorial treatment significantly reduced tumor growth due to a direct activity on Colon-26 tumor cells in vitro and in vivo, while also preserving skeletal muscle mass. Together, our results suggest that as a monotherapy MEK inhibition preserves muscle mass, but when combined with a PI3K/Akt inhibitor exhibits potent anti-tumor activity. Thus, combinatorial therapy might serve as a new approach for the treatment of cancer cachexia. PMID:27811010

  8. Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPβ-regulated atrogin1 expression in cancer cachexia.

    Science.gov (United States)

    Sun, Rulin; Zhang, Santao; Hu, Wenjun; Lu, Xing; Lou, Ning; Yang, Zhende; Chen, Shaoyong; Zhang, Xiaoping; Yang, Hongmei

    2016-07-01

    Muscle wasting is the hallmark of cancer cachexia and is associated with poor quality of life and increased mortality. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has important biological effects in the treatment of muscular dystrophy. To verify whether VPA could ameliorate muscle wasting induced by cancer cachexia, we explored the role of VPA in two cancer cachectic mouse models [induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)] and atrophied C2C12 myotubes [induced by C26 cell conditioned medium (CCM) or LLC cell conditioned medium (LCM)]. Our data demonstrated that treatment with VPA increased the mass and cross-sectional area of skeletal muscles in tumor-bearing mice. Furthermore, treatment with VPA also increased the diameter of myotubes cultured in conditioned medium. The skeletal muscles in cachectic mice or atrophied myotubes treated with VPA exhibited reduced levels of CCAAT/enhancer binding protein beta (C/EBPβ), resulting in atrogin1 downregulation and the eventual alleviation of muscle wasting and myotube atrophy. Moreover, atrogin1 promoter activity in myotubes was stimulated by CCM via activating the C/EBPβ-responsive cis-element and subsequently inhibited by VPA. In contrast to the effect of VPA on the levels of C/EBPβ, the levels of inactivating forkhead box O3 (FoxO3a) were unaffected. In summary, VPA attenuated muscle wasting and myotube atrophy and reduced C/EBPβ binding to atrogin1 promoter locus in the myotubes. Our discoveries indicate that HDAC inhibition by VPA might be a promising new approach for the preservation of skeletal muscle in cancer cachexia. Copyright © 2016 the American Physiological Society.

  9. Importance of functional and metabolic impairments in the characterization of the C-26 murine model of cancer cachexia

    Directory of Open Access Journals (Sweden)

    Kate T. Murphy

    2012-07-01

    Cancer cachexia describes the progressive skeletal muscle wasting and weakness that is associated with many cancers. It impairs quality of life and accounts for >20% of all cancer-related deaths. The main outcome that affects quality of life and mortality is loss of skeletal muscle function and so preclinical models should exhibit similar functional impairments in order to maximize translational outcomes. Mice bearing colon-26 (C-26 tumors are commonly used in cancer cachexia studies but few studies have provided comprehensive assessments of physiological and metabolic impairment, especially those factors that impact quality of life. Our aim was to characterize functional impairments in mildly and severely affected cachectic mice, and determine the suitability of these mice as a preclinical model. Metabolic abnormalities are also evident in cachectic patients and we investigated whether C-26-tumor-bearing mice had similar metabolic aberrations. Twelve-week-old CD2F1 mice received a subcutaneous injection of PBS (control or C-26 tumor cells. After 18–20 days, assessments were made of grip strength, rotarod performance, locomotor activity, whole body metabolism, and contractile properties of tibialis anterior (TA muscles (in situ and diaphragm muscle strips (in vitro. Injection of C-26 cells reduced body and muscle mass, and epididymal fat mass. C-26-tumor-bearing mice exhibited lower grip strength and rotarod performance. Locomotor activity was impaired following C-26 injection, with reductions in movement distance, duration and speed compared with controls. TA muscles from C-26-tumor-bearing mice had lower maximum force (−27% and were more susceptible to fatigue. Maximum specific (normalized force of diaphragm muscle strips was reduced (−10% with C-26 injection, and force during fatiguing stimulation was also lower. C-26-tumor-bearing mice had reduced carbohydrate oxidation and increased fat oxidation compared with controls. The range and consistency of

  10. Importance of functional and metabolic impairments in the characterization of the C-26 murine model of cancer cachexia.

    Science.gov (United States)

    Murphy, Kate T; Chee, Annabel; Trieu, Jennifer; Naim, Timur; Lynch, Gordon S

    2012-07-01

    Cancer cachexia describes the progressive skeletal muscle wasting and weakness that is associated with many cancers. It impairs quality of life and accounts for >20% of all cancer-related deaths. The main outcome that affects quality of life and mortality is loss of skeletal muscle function and so preclinical models should exhibit similar functional impairments in order to maximize translational outcomes. Mice bearing colon-26 (C-26) tumors are commonly used in cancer cachexia studies but few studies have provided comprehensive assessments of physiological and metabolic impairment, especially those factors that impact quality of life. Our aim was to characterize functional impairments in mildly and severely affected cachectic mice, and determine the suitability of these mice as a preclinical model. Metabolic abnormalities are also evident in cachectic patients and we investigated whether C-26-tumor-bearing mice had similar metabolic aberrations. Twelve-week-old CD2F1 mice received a subcutaneous injection of PBS (control) or C-26 tumor cells. After 18-20 days, assessments were made of grip strength, rotarod performance, locomotor activity, whole body metabolism, and contractile properties of tibialis anterior (TA) muscles (in situ) and diaphragm muscle strips (in vitro). Injection of C-26 cells reduced body and muscle mass, and epididymal fat mass. C-26-tumor-bearing mice exhibited lower grip strength and rotarod performance. Locomotor activity was impaired following C-26 injection, with reductions in movement distance, duration and speed compared with controls. TA muscles from C-26-tumor-bearing mice had lower maximum force (-27%) and were more susceptible to fatigue. Maximum specific (normalized) force of diaphragm muscle strips was reduced (-10%) with C-26 injection, and force during fatiguing stimulation was also lower. C-26-tumor-bearing mice had reduced carbohydrate oxidation and increased fat oxidation compared with controls. The range and consistency of

  11. Importance of functional and metabolic impairments in the characterization of the C-26 murine model of cancer cachexia

    Science.gov (United States)

    Murphy, Kate T.; Chee, Annabel; Trieu, Jennifer; Naim, Timur; Lynch, Gordon S.

    2012-01-01

    SUMMARY Cancer cachexia describes the progressive skeletal muscle wasting and weakness that is associated with many cancers. It impairs quality of life and accounts for >20% of all cancer-related deaths. The main outcome that affects quality of life and mortality is loss of skeletal muscle function and so preclinical models should exhibit similar functional impairments in order to maximize translational outcomes. Mice bearing colon-26 (C-26) tumors are commonly used in cancer cachexia studies but few studies have provided comprehensive assessments of physiological and metabolic impairment, especially those factors that impact quality of life. Our aim was to characterize functional impairments in mildly and severely affected cachectic mice, and determine the suitability of these mice as a preclinical model. Metabolic abnormalities are also evident in cachectic patients and we investigated whether C-26-tumor-bearing mice had similar metabolic aberrations. Twelve-week-old CD2F1 mice received a subcutaneous injection of PBS (control) or C-26 tumor cells. After 18–20 days, assessments were made of grip strength, rotarod performance, locomotor activity, whole body metabolism, and contractile properties of tibialis anterior (TA) muscles (in situ) and diaphragm muscle strips (in vitro). Injection of C-26 cells reduced body and muscle mass, and epididymal fat mass. C-26-tumor-bearing mice exhibited lower grip strength and rotarod performance. Locomotor activity was impaired following C-26 injection, with reductions in movement distance, duration and speed compared with controls. TA muscles from C-26-tumor-bearing mice had lower maximum force (−27%) and were more susceptible to fatigue. Maximum specific (normalized) force of diaphragm muscle strips was reduced (−10%) with C-26 injection, and force during fatiguing stimulation was also lower. C-26-tumor-bearing mice had reduced carbohydrate oxidation and increased fat oxidation compared with controls. The range and

  12. Anormalidades neuromuscular no desuso, senilidade e caquexia Neuromuscular abnormalities in disuse, cachexia and ageing

    Directory of Open Access Journals (Sweden)

    João Aris Kouyoumdjian

    1993-09-01

    Full Text Available É feita revisão de literatura sobre as principais alterações do sistema neuromuscular no desuso, senilidade e caquexia no ser humano e em modelos animais. A diminuição do diâmetro das fibras musculares após período de inatividade/imobilidade (desuso deve-se à perda de miofibrilas periféricas não ocorrendo formação de core-targetóides ou diminuição da atividade da miofosforilase, próprias da desnervação; mantêm-se a liberação espontânea de acetilcolina e fatores tróficos na junção mio-neural; em geral são afetadas preferencialmente fibras II, que podem assumir forma angular. Existe um processo contínuo intrínseco de envelhecimento de nervos e músculos, com desnervação e reinervação lenta e progressiva; o número de unidades motoras se reduz após 60 anos, sem ocorrência de atividade elétrica desnervatória; a quantidade de acetilcolina liberada nos neurônios terminais e a capacidade máxima de utilização de oxigênio estão diminuídas; a redução da capacidade oxidativa mitocondrial pode explicar o aumento de fibras I, mantendo-se o equilíbrio energético. Após poucas semanas de caquexia as fibras musculares podem ter o diâmetro reduzido em 30%, essa redução ocorre em ordem decrescente nos músculos dos membros inferiores, superiores e tronco; existe atrofia II preferencial com fibras angulares ocasionais, redução de RNA/síntese proteica, mantendo-se DNA normal.Cachexia, ageing and disuse and their effects on the human and animals neuromuscular system are reviewed. Disuse induces reduction of muscle fibers (mainly II diameter with peripheral myofibrils lost; there is no core-targetoid or even reduction on myophosphorilase activity, both typical of denervation; the acetylcholine spontaneous release and trophic factors on myoneural junction are maintained; muscle fibers could change to angular shape. Ageing affects nerve and muscle by a continuous and progressive process of denervation and reinner

  13. Oral Treatment with the Ghrelin Receptor Agonist HM01 Attenuates Cachexia in Mice Bearing Colon-26 (C26) Tumors.

    Science.gov (United States)

    Villars, Fabienne O; Pietra, Claudio; Giuliano, Claudio; Lutz, Thomas A; Riediger, Thomas

    2017-05-05

    The gastrointestinal hormone ghrelin reduces energy expenditure and stimulates food intake. Ghrelin analogs are a possible treatment against cancer anorexia-cachexia syndrome (CACS). This study aimed to investigate whether oral treatment with the non-peptidergic ghrelin receptor agonist HM01 counteracts CACS in colon-26 (C26) tumor-bearing mice. The C26 tumor model is characterized by pronounced body weight (BW) loss and muscle wasting in the absence of severe anorexia. We analyzed the time course of BW loss, body composition, muscle mass, bone mineral density, and the cytokines interleukin-6 (IL-6) and macrophage-inhibitory cytokine-1 (MIC-1). Moreover, we measured the expression of the muscle degradation markers muscle RING-finger-protein-1 (MuRF-1) and muscle atrophy F-box (MAFbx). After tumor inoculation, MIC-1 levels increased earlier than IL-6 and both cytokines were elevated before MuRF-1/MAFbx expression increased. Oral HM01 treatment increased BW, fat mass, and neuronal hypothalamic activity in healthy mice. In tumor-bearing mice, HM01 increased food intake, BW, fat mass, muscle mass, and bone mineral density while it decreased energy expenditure. These effects appeared to be independent of IL-6, MIC-1, MuRF-1 or MAFbx, which were not affected by HM01. Therefore, HM01 counteracts cachectic body weight loss under inflammatory conditions and is a promising compound for the treatment of cancer cachexia in the absence of severe anorexia.

  14. Hypothalamic actions of tumor necrosis factor alpha provide the thermogenic core for the wastage syndrome in cachexia.

    Science.gov (United States)

    Arruda, Ana Paula; Milanski, Marciane; Romanatto, Talita; Solon, Carina; Coope, Andressa; Alberici, Luciane C; Festuccia, William T; Hirabara, Sandro M; Ropelle, Eduardo; Curi, Rui; Carvalheira, José B; Vercesi, Aníbal E; Velloso, Licio A

    2010-02-01

    TNFalpha is an important mediator of catabolism in cachexia. Most of its effects have been characterized in peripheral tissues, such as skeletal muscle and fat. However, by acting directly in the hypothalamus, TNFalpha can activate thermogenesis and modulate food intake. Here we show that high concentration TNFalpha in the hypothalamus leads to increased O(2) consumption/CO(2) production, increased body temperature, and reduced caloric intake, resulting in loss of body mass. Most of the thermogenic response is produced by beta 3-adrenergic signaling to the brown adipose tissue (BAT), leading to increased BAT relative mass, reduction in BAT lipid quantity, and increased BAT mitochondria density. The expression of proteins involved in BAT thermogenesis, such as beta 3-adrenergic receptor, peroxisomal proliferator-activated receptor-gamma coactivator-1 alpha, and uncoupling protein-1, are increased. In the hypothalamus, TNFalpha produces reductions in neuropeptide Y, agouti gene-related peptide, proopiomelanocortin, and melanin-concentrating hormone, and increases CRH and TRH. The activity of the AMP-activated protein kinase signaling pathway is also decreased in the hypothalamus of TNFalpha-treated rats. Upon intracerebroventricular infliximab treatment, tumor-bearing and septic rats present a significantly increased survival. In addition, the systemic inhibition of beta 3-adrenergic signaling results in a reduced body mass loss and increased survival in septic rats. These data suggest hypothalamic TNFalpha action to be important mediator of the wastage syndrome in cachexia.

  15. A Ketogenic Formula Prevents Tumor Progression and Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice

    Directory of Open Access Journals (Sweden)

    Kentaro Nakamura

    2018-02-01

    Full Text Available Low-carbohydrate, high-fat diets (ketogenic diets might prevent tumor progression and could be used as supportive therapy; however, few studies have addressed the effect of such diets on colorectal cancer. An infant formula with a ketogenic composition (ketogenic formula; KF is used to treat patients with refractory epilepsy. We investigated the effect of KF on cancer and cancer cachexia in colon tumor-bearing mice. Mice were randomized into normal (NR, tumor-bearing (TB, and ketogenic formula (KF groups. Colon 26 cells were inoculated subcutaneously into TB and KF mice. The NR and TB groups received a standard diet, and the KF mice received KF ad libitum. KF mice preserved their body, muscle, and carcass weights. Tumor weight and plasma IL-6 levels were significantly lower in KF mice than in TB mice. In the KF group, energy intake was significantly higher than that in the other two groups. Blood ketone body concentrations in KF mice were significantly elevated, and there was a significant negative correlation between blood ketone body concentration and tumor weight. Therefore, KF may suppress the progression of cancer and the accompanying systemic inflammation without adverse effects on weight gain, or muscle mass, which might help to prevent cancer cachexia.

  16. Anamorelin hydrochloride in the treatment of cancer anorexia–cachexia syndrome: design, development, and potential place in therapy

    Directory of Open Access Journals (Sweden)

    Graf SA

    2017-08-01

    Full Text Available Solomon A Graf,1–3 Jose M Garcia4,5 1Veterans Affairs Puget Sound Health Care System, 2Department of Medicine, Division of Medical Oncology, University of Washington School of Medicine, 3Clinical Research Division, Fred Hutchinson Cancer Research Center, 4Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, 5Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, WA, USA Abstract: Cancer anorexia–cachexia syndrome (CACS is a complex and largely untreatable paraneoplastic complication common in advanced cancer. It is associated with profoundly deleterious effects on quality of life and survival. Since its discovery over a decade ago, anamorelin hydrochloride (anamorelin, a mimetic of the growth hormone secretagogue ghrelin, has shown considerable promise in ameliorating components of CACS when administered to patients with advanced cancer, including loss of lean body mass and reversal of anorexia. This review summarizes the development of anamorelin and its safety and efficacy in clinical investigations. The potential future role of anamorelin in treating CACS is also discussed. Keywords: anamorelin, cachexia, anorexia, ghrelin, non-small cell lung cancer

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

    Science.gov (United States)

    Tsai, V W W; Lin, S; Brown, D A; Salis, A; Breit, S N

    2016-02-01

    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.

  18. Evaluation of a psychoeducational intervention for patients with advanced cancer who have cachexia and their lay carers (EPACaCC): study protocol.

    Science.gov (United States)

    Reid, Joanne; Scott, David; Santin, Olinda; Cardwell, Chris R; Donnelly, Michael; Kernohan, W George; O'Halloran, Peter Dominic; Regan, Joan; Porter, Sam

    2014-05-01

    To evaluate a psychoeducational intervention for patients with advanced cancer who have cachexia and their lay carers. Cachexia is a frequent and devastating syndrome of advanced cancer. It has an impact on patients biologically, psychologically and socially and has profound impact on their lay carers. Prior research has predominately focused on the biological components of cachexia and associated potential treatment modalities. At present, there is no standardized supportive healthcare intervention in current practice that targets the psychosocial impact of this syndrome. A pragmatic multicentre randomized controlled trial. Patient/carer dyads (n = 200) will be recruited into a randomized controlled trial of a DVD intervention for cachexia management. The sample will be recruited from two urban hospices in the UK. The primary outcome measure will be the General Health Questionnaire-12. Additional questionnaires focusing on distress, readiness to give care and coping skills will be used as secondary outcome measures. In addition, lay carers in the intervention group will be asked to participate in semi-structured interviews following the death of their loved one. Both Office for Research Ethics Committee approval and local governance approval at both hospices have been obtained as of February 2013. This is the first time that a psychoeducational DVD has been tested in a randomized controlled trial in this population. Dissemination of findings will make a significant contribution to international knowledge and understanding in this area. Findings will inform education, practice and policy. © 2013 John Wiley & Sons Ltd.

  19. Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia

    DEFF Research Database (Denmark)

    Moraes, Leonardo N; Fernandez, Geysson J; Vechetti-Júnior, Ivan J

    2017-01-01

    Cardiac cachexia (CC) is a common complication of heart failure (HF) associated with muscle wasting and poor patient prognosis. Although different mechanisms have been proposed to explain muscle wasting during CC, its pathogenesis is still not understood. Here, we described an integrative analysis...

  20. Expression of angiogenic switch, cachexia and inflammation factors at the crossroad in undifferentiated thyroid carcinoma with BRAF(V600E).

    Science.gov (United States)

    Husain, Amjad; Hu, Nina; Sadow, Peter M; Nucera, Carmelo

    2016-10-01

    Cachexia is the result of complex metabolic alterations which cause morbidity and mortality in patients with advanced cancers including undifferentiated (anaplastic) thyroid carcinoma (ATC). ATC is a lethal disease with limited therapeutic options and unclear etiology for cachexia. We hypothesize that the BRAF(V600E) oncoprotein triggers microvascular endothelial cell tubule formation (in vitro angiogenesis) by means of factors which play a crucial role in angiogenic switch, inflammation/immune response and cachexia. We use human ATC cells and applied multiplex ELISA assay to screen for and measure angiogenic/cachectic and pro-inflammatory factors in the ATC-derived secretome. We find that vemurafenib anti-BRAF(V600E) therapy significantly reduces secreted VEGFA, VEGFC and IL6 protein levels compared to vehicle-treated ATC cells. As a result, the secretome from vemurafenib-treated ATC cells inhibits microvascular endothelial cell-related in vitro angiogenesis. Furthermore, ATC clinical samples express VEGFA, VEGFC and IL6 proteins. Our results suggest that angiogenic/cachectic and pro-inflammatory/immune response factors could play a crucial role in BRAF(V600E)-positive human ATC aggressiveness. Understanding the extent to which microenvironment-associated angiogenic factors participate in cachexia and cancer metabolism in advanced thyroid cancers will reveal new biomarkers and foster novel therapeutic approaches. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Endoplasmic Reticulum Stress, Calcium Dysregulation and Altered Protein Translation: Intersection of Processes That Contribute to Cancer Cachexia Induced Skeletal Muscle Wasting.

    Science.gov (United States)

    Isaac, Stephanie T; Tan, Timothy C; Polly, Patsie

    2016-01-01

    Cancer cachexia is a debilitating paraneoplastic wasting syndrome characterized by skeletal muscle depletion and unintentional weight loss. It affects up to 50-80% of patients with cancer and directly accounts for one-quarter of cancer-related deaths due to cardio-respiratory failure. Muscle weakness, one of the hallmarks of this syndrome, has been postulated to be due to a combination of muscle breakdown, dysfunction and decrease in the ability to repair, with effective treatment strategies presently limited. Excessive inflammatory cytokine levels due to the host-tumor interaction, such as Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α, are hypothesised to drive this pathological process but the specific mechanisms by which these cytokines produce skeletal muscle dysfunction in cancer cachexia remain undefined. Endoplasmic Reticulum (ER) stress and the associated disruptions in calcium signaling have been implicated in cytokine-mediated disruptions in skeletal muscle and function. Disrupted ER stress-related processes such as the Unfolded Protein Response (UPR), calcium homeostasis and altered muscle protein synthesis have been reported in clinical and experimental cachexia and other inflammation-driven muscle diseases such as myositis, potentially suggesting a link between increased IL-6 and TNF-α and ER stress in skeletal muscle cells. As the concept of upregulated ER stress in skeletal muscle cells due to elevated cytokines is novel and potentially very relevant to our understanding of cancer cachexia, this review aims to examine the potential relationship between inflammatory cytokine mediated muscle breakdown and ER stress, in the context of cancer cachexia, and to discuss the molecular signaling pathways underpinning this pathology.

  2. Anamorelin for cancer anorexia-cachexia syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Bai, Yu; Hu, Yunxia; Zhao, Yanhua; Yu, Xizhong; Xu, Junwei; Hua, Zhiyun; Zhao, Zhiqiang

    2017-05-01

    The aim of this study was to evaluate the therapeutic effects of Anamorelin on patients with cancer anorexia-cachexia syndrome (CACS) based on a meta-analysis of published randomized trials. We searched PubMed, Embase, Medline, and the Cochrane Central Register of Controlled Trials databases. Data from each selected study were evaluated individually. All continuous outcomes were calculated by the mean difference or standardized mean difference with 95% confidence interval for each study. Heterogeneity was assessed by using the Chi2 test at a significance level of P  50% indicated substantial heterogeneity). At last, four studies were included from 284 records. In three studies, lean body mass was reported and there was a significant difference between placebo and Anamorelin groups (P < 0.00001), without significant heterogeneity (I 2 = 0%). All the four studies reported the body weight change from baseline, and there was significant difference between placebo and Anamorelin groups (P = 0.007), but with high heterogeneity (I 2 = 97%). Two studies reported Anderson Symptom Assessment Scale (ASAS) score, and Anamorelin significantly increased the total ASAS score of CACS patients (P < 0.00001), without any heterogeneity (I 2 = 0%). Three studies reported non-dominant handgrip strength, and there was no significant difference between Anamorelin and placebo groups (P = 0.16). Three studies reported insulin-like growth factor-1 level, and there was significant difference between Anamorelin and placebo groups (P = 0.02), but with high heterogeneity (I 2 = 96%). Three studies reported IGF binding protein-3 concentration. Anamorelin significantly increased such concentration compared with placebo did (P < 0.00001). However, there was still higher heterogeneity (I 2 = 59%). All the included studies reported adverse events. Compared with placebo, Anamorelin induced fewer adverse events, but there was no significant difference between the two groups

  3. Underweight, Markers of Cachexia, and Mortality in Acute Myocardial Infarction: A Prospective Cohort Study of Elderly Medicare Beneficiaries.

    Science.gov (United States)

    Bucholz, Emily M; Krumholz, Hannah A; Krumholz, Harlan M

    2016-04-01

    Underweight patients are at higher risk of death after acute myocardial infarction (AMI) than normal weight patients; however, it is unclear whether this relationship is explained by confounding due to cachexia or other factors associated with low body mass index (BMI). This study aimed to answer two questions: (1) does comprehensive risk adjustment for comorbid illness and frailty measures explain the higher mortality after AMI in underweight patients, and (2) is the relationship between underweight and mortality also observed in patients with AMI who are otherwise without significant chronic illness and are presumably free of cachexia? We analyzed data from the Cooperative Cardiovascular Project, a cohort-based study of Medicare beneficiaries hospitalized for AMI between January 1994 and February 1996 with 17 y of follow-up and detailed clinical information to compare short- and long-term mortality in underweight and normal weight patients (n = 57,574). We used Cox proportional hazards regression to investigate the association of low BMI with 30-d, 1-y, 5-y, and 17-y mortality after AMI while adjusting for patient comorbidities, frailty measures, and laboratory markers of nutritional status. We also repeated the analyses in a subset of patients without significant comorbidity or frailty. Of the 57,574 patients with AMI included in this cohort, 5,678 (9.8%) were underweight and 51,896 (90.2%) were normal weight at baseline. Underweight patients were older, on average, than normal weight patients and had a higher prevalence of most comorbidities and measures of frailty. Crude mortality was significantly higher for underweight patients than normal weight patients at 30 d (25.2% versus 16.4%, p underweight patients had a 13% higher risk of 30-d death and a 26% higher risk of 17-y death than normal weight patients (30-d hazard ratio [HR] 1.13, 95% CI 1.07-1.20; 17-y HR 1.26, 95% CI 1.23-1.30). Survival curves for underweight and normal weight patients separated early

  4. Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer-chemotherapy toxicity and prognostic value.

    Science.gov (United States)

    Srdic, Drazena; Plestina, Sanja; Sverko-Peternac, Ana; Nikolac, Nora; Simundic, Ana-Maria; Samarzija, Miroslav

    2016-11-01

    Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer. The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical markers (CRP, IL-6, protein, and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment. Between December 2013 and April 2015, the prospective cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases "Jordanovac," was evaluated. Anthropometric measurements and biochemical data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross-sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively. One hundred patients with advanced lung cancer were recruited: 67 were male and median age was 64 years. The median time to disease progression was 187 days. The prevalence of cachexia and sarcopenia in study cohort was 69 and 47 %, respectively. CRP, IL-6, and albumin concentration in cachectic compared to non-cachectic patients

  5. Can the Serum Level of Myostatin be Considered as an Informative Factor for Cachexia Prevention in Patients with Medullary Thyroid Cancer?

    Science.gov (United States)

    Hedayati, Mehdi; Nozhat, Zahra; Hannani, Masoomeh

    2016-01-01

    Thyroid cancer, the most common endocrine neoplasia, consists of four main types of carcinomas: papillary, follicular, and anaplastic, all with thyroid follicular origin, and medullary thyroid cancer (MTC) related to para-follicular cells. Cronic diseases such as diverse cancers may be associated with cachexia, especially at advanced stage. Cancer-induced cachexia is associated with diminished quality of life, functional performance, reduced response to antitumor therapy, and increased morbidity and mortality. Myostatin (Mst) is one of the outstanding molecules in the skeletal muscle loss process in cancer and it may be released by both skeletal muscle and cachexia-inducing tumors. Recently changes in serum levels of Mst have been identified as an important factor of cancer-induced cachexia. The goal of this study was to assessserum Mst levels in MTC patients. In this descriptive and case-control study, 90 participants were selected, comprising 45 MTC patients (20 males, 29±13.9 years, 25 females, 29±14.5 years) and 45 control individuals (25 males, 23.1±11.6 years, 20 females, 31.5±14.4 years). Serum Mst was determined using an ELISA kit and body mass index (BMI) was calculated by weight and height measurements. The Kolmogorov Simonov test showed a normal distribution for log transformed Mst serum levels in both case and control groups. Geometric means were 5.9 and 8.2 ng/ml respectively, and a significant difference was found according to the independent t-test results (Pcachexia in MTC patients, especially in females.

  6. An Immune-Modulating Diet in Combination with Chemotherapy Prevents Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice.

    Science.gov (United States)

    Nakamura, Kentaro; Sasayama, Akina; Takahashi, Takeshi; Yamaji, Taketo

    2015-01-01

    Cancer cachexia is characterized by muscle wasting caused partly by systemic inflammation. We previously demonstrated an immune-modulating diet (IMD), an enteral diet enriched with immunonutrition and whey-hydrolyzed peptides, to have antiinflammatory effects in some experimental models. Here, we investigated whether the IMD in combination with chemotherapy could prevent cancer cachexia in colon 26 tumor-bearing mice. Forty tumor-bearing mice were randomized into 5 groups: tumor-bearing control (TB), low dose 5-fluorouracil (5-FU) and standard diet (LF/ST), low dose 5-FU and IMD (LF/IMD), high dose 5-FU and standard diet (HF/ST) and high dose 5-FU and IMD (HF/IMD). The ST and IMD mice received a standard diet or the IMD ad libitum for 21 days. Muscle mass in the IMD mice was significantly higher than that in the ST mice. The LF/IMD in addition to the HF/ST and HF/IMD mice preserved their body and carcass weights. Plasma prostaglandin E2 levels were significantly lower in the IMD mice than in the ST mice. A combined effect was also observed in plasma interleukin-6, glucose, and vascular endothelial growth factor levels. Tumor weight was not affected by different diets. In conclusion, the IMD in combination with chemotherapy prevented cancer cachexia without suppressing chemotherapeutic efficacy.

  7. Growth hormone secretagogues hexarelin and JMV2894 protect skeletal muscle from mitochondrial damages in a rat model of cisplatin-induced cachexia.

    Science.gov (United States)

    Sirago, Giuseppe; Conte, Elena; Fracasso, Flavio; Cormio, Antonella; Fehrentz, Jean-Alain; Martinez, Jean; Musicco, Clara; Camerino, Giulia Maria; Fonzino, Adriano; Rizzi, Laura; Torsello, Antonio; Lezza, Angela Maria Serena; Liantonio, Antonella; Cantatore, Palmiro; Pesce, Vito

    2017-10-12

    Chemotherapy can cause cachexia, which consists of weight loss associated with muscle atrophy. The exact mechanisms underlying this skeletal muscle toxicity are largely unknown and co-therapies to attenuate chemotherapy-induced side effects are lacking. By using a rat model of cisplatin-induced cachexia, we here characterized the mitochondrial homeostasis in tibialis anterior cachectic muscle and evaluated the potential beneficial effects of the growth hormone secretagogues (GHS) hexarelin and JMV2894 in this setting. We found that cisplatin treatment caused a decrease in mitochondrial biogenesis (PGC-1α, NRF-1, TFAM, mtDNA, ND1), mitochondrial mass (Porin and Citrate synthase activity) and fusion index (MFN2, Drp1), together with changes in the expression of autophagy-related genes (AKT/FoxO pathway, Atg1, Beclin1, LC3AII, p62) and enhanced ROS production (PRX III, MnSOD). Importantly, JMV2894 and hexarelin are capable to antagonize this chemotherapy-induced mitochondrial dysfunction. Thus, our findings reveal a key-role played by mitochondria in the mechanism responsible for GHS beneficial effects in skeletal muscle, strongly indicating that targeting mitochondrial dysfunction might be a promising area of research in developing therapeutic strategies to prevent or limit muscle wasting in cachexia.

  8. Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model--a study based on data from an international multicentre project (EPCRC-CSA).

    Science.gov (United States)

    Blum, D; Stene, G B; Solheim, T S; Fayers, P; Hjermstad, M J; Baracos, V E; Fearon, K; Strasser, F; Kaasa, S

    2014-08-01

    Weight loss limits cancer therapy, quality of life and survival. Common diagnostic criteria and a framework for a classification system for cancer cachexia were recently agreed upon by international consensus. Specific assessment domains (stores, intake, catabolism and function) were proposed. The aim of this study is to validate this diagnostic criteria (two groups: model 1) and examine a four-group (model 2) classification system regarding these domains as well as survival. Data from an international patient sample with advanced cancer (N = 1070) were analysed. In model 1, the diagnostic criteria for cancer cachexia [weight loss/body mass index (BMI)] were used. Model 2 classified patients into four groups 0-III, according to weight loss/BMI as a framework for cachexia stages. The cachexia domains, survival and sociodemographic/medical variables were compared across models. Eight hundred and sixty-one patients were included. Model 1 consisted of 399 cachectic and 462 non-cachectic patients. Cachectic patients had significantly higher levels of inflammation, lower nutritional intake and performance status and shorter survival. In model 2, differences were not consistent; appetite loss did not differ between group III and IV, and performance status not between group 0 and I. Survival was shorter in group II and III compared with other groups. By adding other cachexia domains to the model, survival differences were demonstrated. The diagnostic criteria based on weight loss and BMI distinguish between cachectic and non-cachectic patients concerning all domains (intake, catabolism and function) and is associated with survival. In order to guide cachexia treatment a four-group classification model needs additional domains to discriminate between cachexia stages. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Combined effect of aerobic interval training and selenium nanoparticles on expression of IL-15 and IL-10/TNF-α ratio in skeletal muscle of 4T1 breast cancer mice with cachexia.

    Science.gov (United States)

    Molanouri Shamsi, M; Chekachak, S; Soudi, S; Quinn, L S; Ranjbar, K; Chenari, J; Yazdi, M H; Mahdavi, M

    2017-02-01

    Cancer cachexia is characterized by inflammation, loss of skeletal muscle and adipose tissue mass, and functional impairment. Oxidative stress and inflammation are believed to regulate pathways controlling skeletal muscle wasting. The aim of this study was to determine the effects of aerobic interval training and the purported antioxidant treatment, selenium nanoparticle supplementation, on expression of IL-15 and inflammatory cytokines in 4T1 breast cancer-bearing mice with cachexia. Selenium nanoparticle supplementation accelerated cachexia symptoms in tumor-bearing mice, while exercise training prevented muscle wasting in tumor-bearing mice. Also, aerobic interval training enhanced the anti-inflammatory indices IL-10/TNF-α ratio and IL-15 expression in skeletal muscle in tumor-bearing mice. However, combining exercise training and antioxidant supplementation prevented cachexia and muscle wasting and additionally decreased tumor volume in 4T1 breast cancer mice. These finding suggested that combining exercise training and antioxidant supplementation could be a strategy for managing tumor volume and preventing cachexia in breast cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. A hypothesis for a possible synergy between ghrelin and exercise in patients with cachexia: Biochemical and physiological bases.

    Science.gov (United States)

    Fuoco, Domenico; Kilgour, Robert D; Vigano, Antonio

    2015-12-01

    This article reviews the biochemical and physiological observations underpinning the synergism between ghrelin and ghrelin agonists with exercise, especially progressive resistance training that has been shown to increase muscle mass. The synergy of ghrelin agonists and physical exercise could be beneficial in conditions where muscle wasting is present, such as that found in patients with advanced cancer. The principal mechanism that controls muscle anabolism following the activation of the ghrelin receptor in the central nervous system involves the release of growth hormone/insulin-like growth factor-1 (GH/IGF-1). GH/IGF-1 axis has a dual pathway of action on muscle growth: (a) a direct action on muscle, bone and fat tissue and (b) an indirect action via the production of both muscle-restricted mIGF-1 and anti-cachectic cytokines. Progressive resistance training is a potent inducer of the secretion the muscle-restricted IGF-1 (mIGF-1) that enhances protein synthesis, increases lean body mass and eventually leads to the improvement of muscle strength. Thus, the combination of ghrelin administration with progressive resistance training may serve to circumvent ghrelin resistance and further reduce muscle wasting, which are commonly associated with cachexia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Dual Inhibition of MEK and PI3K/Akt Rescues Cancer Cachexia through both Tumor-Extrinsic and -Intrinsic Activities.

    Science.gov (United States)

    Talbert, Erin E; Yang, Jennifer; Mace, Thomas A; Farren, Matthew R; Farris, Alton B; Young, Gregory S; Elnaggar, Omar; Che, Zheng; Timmers, Cynthia D; Rajasekera, Priyani; Maskarinec, Jennifer M; Bloomston, Mark; Bekaii-Saab, Tanios; Guttridge, Denis C; Lesinski, Gregory B

    2017-02-01

    Involuntary weight loss, a part of the cachexia syndrome, is a debilitating comorbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses but surprisingly gained weight and increased their skeletal muscle mass. This implied that MEK inhibition might be anticachectic. To test this potential effect of MEK inhibition, we utilized the established Colon-26 model of cancer cachexia and the MEK1/2 inhibitor MEK162. Results showed that MEK inhibition effectively prevented muscle wasting. Importantly, MEK162 retained its ability to spare muscle loss even in mice bearing a Colon-26 clone resistant to the MEK inhibitor, demonstrating that the effects of blocking MEK are at least in part independent of the tumor. Because single-agent MEK inhibitors have been limited as a first-line targeted therapy due to compensatory activation of other oncogenic signaling pathways, we combined MEK162 with the PI3K/Akt inhibitor buparlisib. Results showed that this combinatorial treatment significantly reduced tumor growth due to a direct activity on Colon-26 tumor cells in vitro and in vivo, while also preserving skeletal muscle mass. Together, our results suggest that as a monotherapy, MEK inhibition preserves muscle mass, but when combined with a PI3K/Akt inhibitor exhibits potent antitumor activity. Thus, combinatorial therapy might serve as a new approach for the treatment of cancer cachexia. Mol Cancer Ther; 16(2); 344-56. ©2016 AACRSee related article by Kobayashi et al., p. 357. ©2016 American Association for Cancer Research.

  12. Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs.

    Science.gov (United States)

    Barreto, Rafael; Waning, David L; Gao, Hongyu; Liu, Yunlong; Zimmers, Teresa A; Bonetto, Andrea

    2016-07-12

    Cachexia affects the majority of cancer patients, with currently no effective treatments. Cachexia is defined by increased fatigue and loss of muscle function resulting from muscle and fat depletion. Previous studies suggest that chemotherapy may contribute to cachexia, although the causes responsible for this association are not clear. The purpose of this study was to investigate the mechanism(s) associated with chemotherapy-related effects on body composition and muscle function. Normal mice were administered chemotherapy regimens used for the treatment of colorectal cancer, such as Folfox (5-FU, leucovorin, oxaliplatin) or Folfiri (5-FU, leucovorin, irinotecan) for 5 weeks. The animals that received chemotherapy exhibited concurrent loss of muscle mass and muscle weakness. Consistently with previous findings, muscle wasting was associated with up-regulation of ERK1/2 and p38 MAPKs. No changes in ubiquitin-dependent proteolysis or in the expression of TGFβ-family members were detected. Further, marked decreases in mitochondrial content, associated with abnormalities at the sarcomeric level and with increase in the number of glycolytic fibers were observed in the muscle of mice receiving chemotherapy. Finally, ACVR2B/Fc or PD98059 prevented Folfiri-associated ERK1/2 activation and myofiber atrophy in C2C12 cultures. Our findings demonstrate that chemotherapy promotes MAPK-dependent muscle atrophy as well as mitochondrial depletion and alterations of the sarcomeric units. Therefore, these findings suggest that chemotherapy potentially plays a causative role in the occurrence of muscle loss and weakness. Moreover, the present observations provide a strong rationale for testing ACVR2B/Fc or MEK1 inhibitors in combination with anticancer drugs as novel strategies aimed at preventing chemotherapy-associated muscle atrophy.

  13. Weight loss, appetite loss and food intake in cancer patients with cancer cachexia: three peas in a pod? - analysis from a multicenter cross sectional study.

    Science.gov (United States)

    Solheim, Tora S; Blum, David; Fayers, Peter M; Hjermstad, Marianne J; Stene, Guro B; Strasser, Florian; Kaasa, Stein

    2014-04-01

    How to assess cachexia is a barrier both in research and in clinical practice. This study examines the need for assessing both reduced food intake and loss of appetite, to see if these variables can be used interchangeably. A secondary aim is to assess the variance explained by food intake, appetite and weight loss by using tumor-related factors, symptoms and biological markers as explanatory variables. One thousand and seventy patients with incurable cancer were registered in an observational, cross sectional multicenter study. A total of 885 patients that had complete data on food intake (PG-SGA), appetite (EORTC QLQ-C30) and weight loss were included in the present analysis. The association between reduced food intake and appetite loss was assessed using Spearman's correlation. To find the explained variance of the three symptoms a multivariate analysis was performed. The mean age was 62 years with a mean survival of 247 days and a mean Karnofsky performance status of 72. Thirteen percent of the patients who reported eating less than normal had good appetite and 25% who had unchanged or increased food intake had reduced appetite. Correlation between appetite loss and food intake was 0.50. Explained variance for the regression models was 44% for appetite loss, 27% for food intake and only 13% for weight loss. Both appetite loss and food intake should be assessed in cachectic patients since conscious control of eating may sometimes overcome appetite loss. The low explained variance for weight loss is probably caused by the need for more knowledge about metabolism and inflammation, and is consistent with the cancer cachexia definition that claims that in cachexia weight loss is not caused by reduced food intake alone. The questions concerning appetite loss from EORTC-QLQ C30 and food intake from PG-SGA seem practical and informative when dealing with advanced cancer patients.

  14. Zinc-α2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia

    OpenAIRE

    Bing, Chen; Bao, Yi; Jenkins, John; Sanders, Paul; Manieri, Monia; Cinti, Saverio; Tisdale, Michael J.; Trayhurn, Paul

    2004-01-01

    Zinc-α2-glycoprotein (ZAG), a 43-kDa protein, is overexpressed in certain human malignant tumors and acts as a lipid-mobilizing factor to stimulate lipolysis in adipocytes leading to cachexia in mice implanted with ZAG-producing tumors. Because white adipose tissue (WAT) is an endocrine organ secreting a wide range of protein factors, including those involved in lipid metabolism, we have investigated whether ZAG is produced locally by adipocytes. ZAG mRNA was detected by RT-PCR in the mouse W...

  15. Relation between hypermetabolism, cachexia, and survival in cancer patients: a prospective study in 390 cancer patients before initiation of anticancer therapy.

    Science.gov (United States)

    Vazeille, Clara; Jouinot, Anne; Durand, Jean-Philippe; Neveux, Nathalie; Boudou-Rouquette, Pascaline; Huillard, Olivier; Alexandre, Jérôme; Cynober, Luc; Goldwasser, François

    2017-05-01

    Background: Cachexia is a major cause of death in cancer patients. The role of hypermetabolism in cancer cachexia remains unclear.Objective: We studied the relation between resting energy expenditure (REE), the estimated energy balance, clinical and biological markers of cachexia, and survival.Design: REE was measured with the use of indirect calorimetry in cancer patients before the initiation of anticancer therapies. Hypermetabolic, normometabolic, and hypometabolic patients were identified with the use of Boothby's standard. Weight loss, performance status (PS), C-reactive protein (CRP), albumin, the nutritional risk index, daily energy intake, energy balance (equal to daily energy intakes minus the REE), and survival were recorded.Results: Of 390 enrolled patients, 49% of subjects were hypermetabolic, 30% of subjects were normometabolic, and 21% of subjects were hypometabolic. Mean daily energy intakes did not differ significantly between the 3 groups. Hypermetabolic patients, compared with normometabolic patients, were more likely to have a negative energy balance [45% compared with 32%, respectively; OR: 1.74 (95% CI: 1.05, 2.91); P = 0.024], weight loss >5% [48% compared with 34%, respectively; OR: 1.83 (95% CI: 1.11, 3.04); P = 0.013], PS ≥2 [40% compared with 29%, respectively; OR: 1.70 (95% CI: 1.01, 2.88); P = 0.038], and CRP concentrations ≥10 mg/L [52% compared with 33%, respectively; OR: 2.2 (95% CI: 1.33, 3.66); P = 0.001]. In metastatic patients, compared with normometabolism, hypermetabolism was associated with a reduced median survival [14.6 compared with 21.4 mo, respectively; OR: 1.48 (95% CI: 1.01, 2.17); P = 0.044].Conclusions: Hypermetabolism is correlated with clinical and biological markers of cancer cachexia and is associated with a shorter survival in metastatic cancer patients. The development of therapeutic strategies that aim to blunt hypermetabolism appears warranted. This trial was registered at www.controlled-trials.com as

  16. Functional body composition and related aspects in research on obesity and cachexia: report on the 12th Stock Conference held on 6 and 7 September 2013 in Hamburg, Germany

    NARCIS (Netherlands)

    Muller, M.J; Baracos, V.; Bosy-Westphal, A.; Dulloo, A.G.; Eckel, J.; Fearon, K.C.H.; Hall, K.D.; Pietrobelli, A.; Sorensen, T.I.A.; Speakman, J.; Trayhurn, P.; Visser, M.; Heymsfield, S.B.

    2014-01-01

    The 12th Stock Conference addressed body composition and related functions in two extreme situations, obesity and cancer cachexia. The concept of 'functional body composition' integrates body components into regulatory systems relating the mass of organs and tissues to corresponding in vivo

  17. Study of morphological alterations of the adrenal glands in the neoplastic cachexia Estudo das alterações morfológicas da glândula adrenal na caquexia neoplásica

    Directory of Open Access Journals (Sweden)

    Tânia Longo Mazzuco

    2009-01-01

    Full Text Available Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia. When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker 256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculation and adrenal glands removal for histopathologic analysis by means of hematoxylin and eosin stain. Nutritional parameters, cachexia index and adrenal glands weight, were evaluated. Animals with tumor presented cachexia index of 16,6 ± 4%. Adrenal glands average weight was significantly higher in the tumor group (40 mg ± 10 than in the control group (25 mg ± 3. Adrenal cortex of animals with cachexia showed hypertrophy of the zona fasciculata and reticular layer, with voluminous spongiocytes; vascular congestion and stasis were observed in the medullar region. Results were similar in the pair and ad libitum-fed groups. Animals with cancer cachexia showed compromised morphology of the adrenal glands which showed alterations related to stress response, suggesting increased cathecolamine secretion and activation of the hypothalamus-pituitary-adrenal axis.   Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia. When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker 256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculation and adrenal glands removal for histopathologic analysis by means of hematoxylin and eosin stain. Nutritional

  18. The role of long-chain polyunsaturated fatty acids in the treatment of cancer Cachexia and tumour growth in patients with malignant diseases: A review

    Directory of Open Access Journals (Sweden)

    Elizabeth A Symington

    2008-02-01

    Full Text Available Recent studies show that ω-3 polyunsaturated fatty acids (PUFAs have the capacity to modulate cancer outcomes. The body responds to cancer in the same way that it responds to inflammation and wound healing. Nutrients with anti-inflammatory effects could therefore be expected to play a role in cancer treatment. This review focuses on the role of ω-3 PUFAs in tumourigenesis and cancer cachexia. Studies indicate that eicosapentaenoic acid (EPA supplementation may promote arrest of tumour growth and reduce cell proliferation. Patients need to consume at least 2 g of EPA per day for it to have a therapeutic effect. Positive outcomes related to cachexia include diminished weight loss, increased appetite, improved quality of life and prolonged survival, although there is controversy regarding these clinical outcomes. The effects of ω-3 PUFAs on tumourigenesis and cachexia are viewed in the context of altered lipid and protein metabolism. This altered metabolism usually experienced by cancer patients results in increased formation of proinflammatory eicosanoids and cytokines. Cytokines play an indirect role by stimulating the production of arachidonic acid-derived eicosanoids, which support inflammation, cell proliferation and angiogenesis, and inhibit apoptosis. It can be concluded that ω-3 PUFA supplementation offers a means of augmenting cancer therapy, inhibiting tumourigenesis and possibly contributing to cachexia alleviation. Opsomming Onlangse studies toon dat ω-3-poli-onversadigde vetsure (POVSe oor die vermoë beskik om kankeruitkomste te moduleer. Die liggaam reageer op kanker op dieselfde wyse as wat dit op inflammasie en wondgenesing reageer. Daar kan dus verwag word dat voedingstowwe met ‘n anti-inflammatoriese uitwerking ‘n rol in die behandeling van kanker kan speel. In hierdie oorsig word daar op die rol van ω-3-POVSe in tumorigenese en kankerkageksie gefokus. Studies dui daarop dat eikosapentanoënsuur- (EPS

  19. Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia

    DEFF Research Database (Denmark)

    Moraes, Leonardo N; Fernandez, Geysson J; Vechetti-Júnior, Ivan J

    2017-01-01

    Cardiac cachexia (CC) is a common complication of heart failure (HF) associated with muscle wasting and poor patient prognosis. Although different mechanisms have been proposed to explain muscle wasting during CC, its pathogenesis is still not understood. Here, we described an integrative analysis...... between miRNA and mRNA expression profiles of muscle wasting during CC. Global gene expression profiling identified 1,281 genes and 19 miRNAs differentially expressed in muscle wasting during CC. Several of these deregulated genes are known or putative targets of the altered miRNAs, including miR-29a-3p......, miR-29b-3p, miR-210-5p, miR-214, and miR-489. Gene ontology analysis on integrative mRNA/miRNA expression profiling data revealed miRNA interactions affecting genes that regulate extra-cellular matrix (ECM) organization, proteasome protein degradation, citric acid cycle and respiratory electron...

  20. The role of long-chain polyunsaturated fatty acids in the treatment of cancer Cachexia and tumour growth in patients with malignant diseases: A review

    Directory of Open Access Journals (Sweden)

    Elizabeth A Symington

    2008-11-01

    Full Text Available Recent studies show that ω-3 polyunsaturated fatty acids (PUFAs have the capacity to modulate cancer outcomes. The body responds to cancer in the same way that it responds to inflammation and wound healing. Nutrients with anti-inflammatory effects could therefore be expected to play a role in cancer treatment. This review focuses on the role of ω-3 PUFAs in tumourigenesis and cancer cachexia. Studies indicate that eicosapentaenoic acid (EPA supplementation may promote arrest of tumour growth and reduce cell proliferation. Patients need to consume at least 2 g of EPA per day for it to have a therapeutic effect. Positive outcomes related to cachexia include diminished weight loss, increased appetite, improved quality of life and prolonged survival, although there is controversy regarding these clinical outcomes. The effects of ω-3 PUFAs on tumourigenesis and cachexia are viewed in the context of altered lipid and protein metabolism. This altered metabolism usually experienced by cancer patients results in increased formation of proinflammatory eicosanoids and cytokines. Cytokines play an indirect role by stimulating the production of arachidonic acid-derived eicosanoids, which support inflammation, cell proliferation and angiogenesis, and inhibit apoptosis. It can be concluded that ω-3 PUFA supplementation offers a means of augmenting cancer therapy, inhibiting tumourigenesis and possibly contributing to cachexia alleviation. Opsomming Onlangse studies toon dat ω-3-poli-onversadigde vetsure (POVSe oor die vermoë beskik om kankeruitkomste te moduleer. Die liggaam reageer op kanker op dieselfde wyse as wat dit op inflammasie en wondgenesing reageer. Daar kan dus verwag word dat voedingstowwe met ‘n anti-inflammatoriese uitwerking ‘n rol in die behandeling van kanker kan speel. In hierdie oorsig word daar op die rol van ω-3-POVSe in tumorigenese en kankerkageksie gefokus. Studies dui daarop dat eikosapentanoënsuur- (EPS

  1. A trial assessing N-3 as treatment for injury-induced cachexia (ATLANTIC trial): does a moderate dose fish oil intervention improve outcomes in older adults recovering from hip fracture?

    OpenAIRE

    Cleland Leslie; Fraser Robert; Cobiac Lynne; Villani Anthony; Yaxley Alison; Miller Michelle D; James Michael; Crotty Maria

    2010-01-01

    Abstract Background Proximal femoral fractures are associated with increased morbidity and mortality. Pre-existing malnutrition and weight loss amongst this patient group is of primary concern, with conventional nutrition support being largely ineffective. The inflammatory response post proximal femoral fracture surgery and the subsequent risk of cachexia may explain the inability of conventional high energy high protein management to produce an anabolic response amongst these patients. Omega...

  2. Centella asiatica modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC's).

    Science.gov (United States)

    Naidoo, Dhaneshree Bestinee; Chuturgoon, Anil Amichund; Phulukdaree, Alisa; Guruprasad, Kanive Parashiva; Satyamoorthy, Kapaettu; Sewram, Vikash

    2017-08-01

    Cancer cachexia is associated with increased pro-inflammatory cytokine levels. Centella asiatica (C. asiatica) possesses antioxidant, anti-inflammatory and anti-tumour potential. We investigated the modulation of antioxidants, cytokines and cell death by C. asiatica ethanolic leaf extract (C LE ) in leukaemic THP-1 cells and normal peripheral blood mononuclear cells (PBMC's). Cytotoxcity of C LE was determined at 24 and 72 h (h). Oxidant scavenging activity of C LE was evaluated using the 2, 2-diphenyl-1 picrylhydrazyl (DPPH) assay. Glutathione (GSH) levels, caspase (-8, -9, -3/7) activities and adenosine triphosphate (ATP) levels (Luminometry) were then assayed. The levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10 were also assessed using enzyme-linked immunosorbant assay. C LE decreased PBMC viability between 33.25-74.55% (24 h: 0.2-0.8 mg/ml C LE and 72 h: 0.4-0.8 mg/ml C LE ) and THP-1 viability by 28.404% (72 h: 0.8 mg/ml C LE ) (p < 0.0001). Oxidant scavenging activity was increased by C LE (0.05-0.8 mg/ml) (p < 0.0001). PBMC TNF-α and IL-10 levels were decreased by C LE (0.05-0.8 mg/ml) (p < 0.0001). However, PBMC IL-6 and IL-1β concentrations were increased at 0.05-0.2 mg/ml C LE but decreased at 0.4 mg/ml C LE (p < 0.0001). In THP-1 cells, C LE (0.2-0.8 mg/ml) decreased IL-1β and IL-6 whereas increased IL-10 levels (p < 0.0001). In both cell lines, C LE (0.05-0.2 mg/ml, 24 and 72 h) increased GSH concentrations (p < 0.0001). At 24 h, caspase (-9, -3/7) activities was increased by C LE (0.05-0.8 mg/ml) in PBMC's whereas decreased by C LE (0.2-0.4 mg/ml) in THP-1 cells (p < 0.0001). At 72 h, C LE (0.05-0.8 mg/ml) decreased caspase (-9, -3/7) activities and ATP levels in both cell lines (p < 0.0001). In PBMC's and THP-1 cells, C LE proved to effectively modulate antioxidant activity, inflammatory cytokines and cell death. In THP-1 cells, C LE decreased pro-inflammatory cytokine levels

  3. Anorexia‐cachexia syndrome in hepatoma tumour‐bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC‐1/GDF15

    Science.gov (United States)

    Borner, Tito; Arnold, Myrtha; Ruud, Johan; Breit, Samuel N.; Langhans, Wolfgang; Lutz, Thomas A.; Blomqvist, Anders

    2016-01-01

    Abstract Background The cancer‐anorexia‐cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour‐derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour‐derived macrophage inhibitory cytokine‐1 (MIC‐1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC‐1 in mice. Methods Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC‐1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response. Results In tumour‐bearing sham‐operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer‐induced anorexia or body weight loss. Tumour‐bearing rats had substantially increased MIC‐1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake. Conclusions These findings demonstrate the importance of the AP in the mediation of cancer‐dependent anorexia and body weight loss and support a pathological role of MIC‐1 as a tumour‐derived factor mediating CACS, possibly via an AP

  4. Expressão de genes relacionados à função adrenocortical no estado de caquexia neoplásica = Expression of genes related to the adrenocortical function in the neoplastic cachexia process

    Directory of Open Access Journals (Sweden)

    Nicole de Angelis Scripes

    2009-04-01

    Full Text Available A glândula adrenal tem papel fundamental na resposta neuroendócrina,especialmente em situações em que há comprometimento da homeostasia. No processo de caquexia neoplásica, há prejuízo da homeostasia por alterações nutricionais e metabólicas do câncer em estágio avançado, envolvendo a resposta do eixo hipotálamo-hipófise-adrenal. Neste trabalho, foi utilizado um modelo animal de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais (n=4 foram sacrificados dez dias após a inoculação de células tumorais e a glândula adrenal foi removida. O RNA foi extraído para o estudo da expressão de genes relacionados ao controle da esteroidogênese por RT-PCR semiquantitativa. A análise dos dados demonstrou expressão significativamente reduzida dos genes MC2R (receptor tipo 2 para melacortina, 3ßHSD I (3β-hidroxiesteroidedesidrogenase tipo I e TSPO (proteína translocadora em animais com caquexia neoplásica(valores de P=0,037; 0,0097 e 0,052, respectivamente, revelando falência do córtex da adrenal.The adrenal gland plays a crucial role in the neuroendocrine response, especially in situations where homeostasis is disturbed. In the neoplastic cachexia process, there is homeostasis impairment by nutritional and metabolic alterations of advanced-stage cancer, involving hypothalamus-pituitary-adrenal axis response. In thisassignment, an experimental model of cachexia induced by Walker-256 tumor was performed in Wistar rats. Animals (n=4 were sacrificed 10 days after inoculation of tumor cells, and the adrenal glands were excised. The RNA was isolated for the study of gene expression related to the steroidogenesis control by semi-quantitative RT-PCR. Data analysis showed a significant reduced expression of MC2R (melancortin type 2 receptor, 3ßHSD I (3-beta-hydroxysteroid dehydrogenase type I and TSPO (translocator protein genes in animals with neoplastic cachexia (P=0.037, 0.0097 and 0.052, respectively, revealing

  5. Cachexia and herbal medicine: perspective.

    Science.gov (United States)

    Suzuki, Hajime; Asakawa, Akihiro; Amitani, Haruka; Nakamura, Norifumi; Inui, Akio

    2012-01-01

    Kampo, a form of traditional herbal medical practice, has become a substance of interest for scientific research. Although earlier clinical reports concerning Kampo are abundant, the scientific investigation of Kampo has a very short history. However, the process of acquiring quantifiable clinical trial evidence on herbal medicine is now clearly underway. The development of multi-component herbal medicines capable of targeting multiple sites could be useful both for future drug discovery and for the potential management of complex diseases. Additionally, mechanistic studies and the identification of active compounds could lead to new discoveries in the biological and biomedical sciences. Modern translational research on herbal medicines beyond basic science and clinical perspectives will contribute to the development of new medicines. This review covers the translational aspects of herbal medicine with a focus on cancer anorexiacachexia. The review gives perspective on a new horizon for herbal medicine from a scientific point of view and a basis for the further development of complementary and alternative medicine (CAM) for patients.

  6. Development of ghrelin resistance in a cancer cachexia rat model using human gastric cancer-derived 85As2 cells and the palliative effects of the Kampo medicine rikkunshito on the model

    Science.gov (United States)

    Sawada, Yumi; Hashimoto, Hirofumi; Yoshimura, Mitsuhiro; Ohbuchi, Katsuya; Sudo, Yuka; Suzuki, Masami; Miyano, Kanako; Shiraishi, Seiji; Higami, Yoshikazu; Yanagihara, Kazuyoshi; Hattori, Tomohisa; Kase, Yoshio; Ueta, Yoichi; Uezono, Yasuhito

    2017-01-01

    Cancer cachexia (CC) is a multifactorial disease characterized by decreased food intake and loss of body weight due to reduced musculature with or without loss of fat mass. Patients with gastric cancer have a high incidence of cachexia. We previously established a novel CC rat model induced by human gastric cancer-derived 85As2 cells in order to examine the pathophysiology of CC and identify potential therapeutics. In patients with CC, anorexia is often observed, despite elevation of ghrelin, suggesting that ghrelin resistance may develop in these patients. In this study, we aimed to clarify the occurrence of ghrelin resistance in CC rats accompanied by anorexia and we investigated whether rikkunshito (RKT), a traditional Japanese Kampo medicine that potentiates ghrelin signaling, ameliorated CC-related anorexia through alleviation of ghrelin resistance. 85As2-tumor-bearing rats developed severe CC symptoms, including anorexia and loss of body weight/musculature, with the latter symptoms being greater in cachectic rats than in non-tumor-bearing or pair-fed rats. CC rats showed poor responses to intraperitoneal injection of ghrelin. In CC rats, plasma ghrelin levels were elevated and hypothalamic anorexigenic peptide mRNA levels were decreased, whereas hypothalamic growth hormone secretagogue receptor (GHS-R) mRNA was not affected. In vitro, RKT directly enhanced ghrelin-induced GHS-R activation. RKT administrated orally for 7 days partly alleviated the poor response to ghrelin and ameliorated anorexia without affecting the elevation of plasma ghrelin levels in CC rats. The expression of hypothalamic orexigenic neuropeptide Y mRNA but not hypothalamic GHS-R mRNA was increased by RKT. Thus, the 85As2 cell-induced CC rat model developed ghrelin resistance, possibly contributing to anorexia and body weight loss. The mechanism through which RKT ameliorated anorexia in the CC rat model may involve alleviation of ghrelin resistance by enhancement of ghrelin signaling

  7. Caracterización nutricional del síndrome anorexia-caquexia en el paciente oncológico pediátrico Nutritional characterization of anorexia-cachexia in pediatric oncologic patient

    Directory of Open Access Journals (Sweden)

    Rafael Jiménez García

    2011-12-01

    ísticas nutricionales del síndrome anorexia-caquexia, en relación con el tipo de enfermedad oncológica que presenta el niño.Introduction: the anorexia-cachexia syndrome may be present in the 80 % of patients diagnosed with advanced cancer and it is a very important mortality risk factor. Objective: to characterize according to some indicators of the nutritional status, the anorexia-cachexia syndrome in a group of children involved by this syndrome with oncologic disease. Methods: a prospective and analytical study was conducted including 42 children diagnosed with anorexia-cachexia syndrome by the Nutritional Support Group together with the Oncology-Hematology of the "Juan Manuel Márquez" Reaching Children Hospital from 2000 to 2009. All the patients in the first consultation underwent after made the diagnosis, a anthropometric profile and a minimal metabolic study (conducted 24 hours after it. At the same time the mother was trained in the fill in of survey by reminder of three days to collect information on the quality and quantity of feeding at week after the first consultation. The form designed by the Nutritional Support Group was applied to know some of the features related to habits and food behavior. Results: in children presenting with lymphoproliferative diseases and in those with solid tumors, there is a considerable nutritional deterioration at moment of diagnosis. There were significant differences in relation to indicators of weight loss percentage and velocity of gain weight, and only the albumin -among study metabolic indicators- had a significant difference. Children presenting with solid tumors ingest less calories than those involved by lymphoproliferative diseases and no significant difference in relation to proteins ingested. Conclusions: there are differences in nutritional characteristics of anorexia-cachexia syndrome according to the type of oncologic disease present in child.

  8. L-carnitine and cancer cachexia. II. Effects of lipid emulsion used in total parenteral nutrition on parameters of hemostasis and inflammatory state in L-carnitine deficiency in myocytes.

    Science.gov (United States)

    Szefel, Jarosław; Kruszewski, Wiesław Janusz; Ciesielski, Maciej; Szajewski, Mariusz; Kawecki, Krzysztof; Jankun, Jerzy; Lysiak-Szydłowska, Wiesława

    2012-07-01

    Cancer cachexia (CC), a progressive loss of body mass, leads to malnutrition and deficiencies of essential substances including polyunsaturated fatty acids (PUFAs) and L-carnitine (LC). The availability of these 2 compounds determines the rate of eicosanoid synthesis, which modulates inflammatory processes and hemostasis. We compared the effects of administration of emulsions containing long chain triglycerides (LCTs) relative to a 50:50 mix of medium chain triglycerides (MCTs) with LCTs on hemostasis and inflammatory reactions in patients with CC. The study was conducted on 50 patients with CC (23 women, 27 men) aged 66 ± 11 years with a mean loss in body weight of 21 ± 9% in the previous 6 months. Twenty patients received MCTs/LCTs while 30 received LCTs. Total parenteral nutrition (TPN) was administered using the 'all in one' method (25 kcal/kg/day, protein 1.2 g/kg/day). Selected parameters of coagulation and inflammatory state were evaluated on days 1, 5, 7 and 11 of TPN. Initial concentrations of D-dimers, fibrinogen, plasminogen activator inhibitor type 1 (PAI-1), fibronectin, CRP and IL-6 significantly exceeded the upper limit of the reference values. After 10 days of TPN, we detected significant differences in inflammatory state and hemostasis. Immunological state and hemostasis varied depending on the type of fat emulsion administered. The most likely reasons are the 2-fold higher concentrations of PUFAs in LCTs relative to MCTs/LCTs and a deficiency of LC in skeletal muscles. Both of these factors may contribute to the observed increase in the rate of eicosanoid synthesis.

  9. A trial assessing N-3 as treatment for injury-induced cachexia (ATLANTIC trial: does a moderate dose fish oil intervention improve outcomes in older adults recovering from hip fracture?

    Directory of Open Access Journals (Sweden)

    Cleland Leslie

    2010-10-01

    Full Text Available Abstract Background Proximal femoral fractures are associated with increased morbidity and mortality. Pre-existing malnutrition and weight loss amongst this patient group is of primary concern, with conventional nutrition support being largely ineffective. The inflammatory response post proximal femoral fracture surgery and the subsequent risk of cachexia may explain the inability of conventional high energy high protein management to produce an anabolic response amongst these patients. Omega-3 fatty acids derived from fish oils have been extensively studied for their anti-inflammatory benefits. Due to their anti-inflammatory properties, the benefit of fish oil combined with individualized nutrition support amongst proximal femoral fracture patients post surgery is an attractive potential therapeutic strategy. The aim of the ATLANTIC trial is to assess the potential benefits of an anti-inflammatory dose of fish oil within the context of a 12 week individualised nutrition program, commencing seven days post proximal femoral fracture surgery. Methods/Design This randomized controlled, double blinded trial, will recruit 150 community dwelling elderly patients aged ≥65 years, within seven days of surgery for proximal femoral fracture. Participants will be randomly allocated to receive either a 12 week individualized nutrition support program complemented with 20 ml/day anti-inflammatory dose fish oil (~3.6 g eicosapentaenoic acid, ~2.4 g docosahexanoic acid; intervention, or, a 12 week individualized nutrition support program complemented with 20 ml/day low dose fish oil (~0.36 g eicosapentaenoic acid, ~0.24 g docosahexanoic acid; control. Discussion The ATLANTIC trial is the first of its kind to provide fish oil combined with individualized nutrition therapy as an intervention to address the inflammatory response experienced post proximal femoral fracture surgery amongst elderly patients. The final outcomes of this trial will assist clinicians in

  10. Expressão de genes relacionados à função adrenocortical no estado de caquexia neoplásica - DOI: 10.4025/actascihealthsci.v31i2.6759 Expression of genes related to the adrenocortical function in the neoplastic cachexia process- DOI: 10.4025/actascihealthsci.v31i2.6759

    Directory of Open Access Journals (Sweden)

    Maria Angélica Ehara Watanabe

    2009-09-01

    Full Text Available A glândula adrenal tem papel fundamental na resposta neuroendócrina, especialmente em situações em que há comprometimento da homeostasia. No processo de caquexia neoplásica, há prejuízo da homeostasia por alterações nutricionais e metabólicas do câncer em estágio avançado, envolvendo a resposta do eixo hipotálamo-hipófise-adrenal. Neste trabalho, foi utilizado um modelo animal de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais (n=4 foram sacrificados dez dias após a inoculação de células tumorais e a glândula adrenal foi removida. O RNA foi extraído para o estudo da expressão de genes relacionados ao controle da esteroidogênese por RT-PCR semiquantitativa. A análise dos dados demonstrou expressão significativamente reduzida dos genes MC2R (receptor tipo 2 para melacortina, 3ßHSD I (3ß-hidroxiesteroide-desidrogenase tipo I e TSPO (proteína translocadora em animais com caquexia neoplásica (valores de P=0,037; 0,0097 e 0,052, respectivamente, revelando falência do córtex da adrenal.The adrenal gland plays a crucial role in the neuroendocrine response, especially in situations where homeostasis is disturbed. In the neoplastic cachexia process, there is homeostasis impairment by nutritional and metabolic alterations of advanced-stage cancer, involving hypothalamus-pituitary-adrenal axis response. In this assignment, an experimental model of cachexia induced by Walker-256 tumor was performed in Wistar rats. Animals (n=4 were sacrificed 10 days after inoculation of tumor cells, and the adrenal glands were excised. The RNA was isolated for the study of gene expression related to the steroidogenesis control by semi-quantitative RT-PCR. Data analysis showed a significant reduced expression of MC2R (melancortin type 2 receptor, 3ßHSD I (3-beta-hydroxysteroid dehydrogenase type I and TSPO (translocator protein genes in animals with neoplastic cachexia (P=0.037, 0.0097 and 0.052, respectively, revealing

  11. Caquexia cardíaca Cardiac cachexia

    OpenAIRE

    Alberto Miján; Elvira Martín; Beatriz de Mateo

    2006-01-01

    La insuficiencia cardíaca de carácter crónico (ICC), en especial si afecta al corazón derecho, ocasiona con frecuencia malnutrición. Si esta es grave y se unen otros componentes, puede producirse caquexia cardíaca. Esta se asocia a mayor morbilidad y menor supervivencia de los pacientes que la padecen. Las causas de la caquexia cardíaca son diversas, en general asociadas a mantener balance energético negativo, surgiendo cada vez mayor evidencia que apoya un origen multifactorial de la misma. ...

  12. Obesity paradox, cachexia, frailty, and heart failure.

    Science.gov (United States)

    Lavie, Carl J; De Schutter, Alban; Alpert, Martin A; Mehra, Mandeep R; Milani, Richard V; Ventura, Hector O

    2014-04-01

    Overweight and obesity adversely affect cardiovascular (CV) risk factors and CV structure and function, and lead to a marked increase in the risk of developing heart failure (HF). Despite this, an obesity paradox exists, wherein those who are overweight and obese with HF have a better prognosis than their leaner counterparts, and the underweight, frail, and cachectic have a particularly poor prognosis. In light of this, the potential benefits of exercise training and efforts to improve cardiorespiratory fitness, as well as the potential for weight reduction, especially in severely obese patients with HF, are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Diabetic neuropathic cachexia in a young female

    Directory of Open Access Journals (Sweden)

    Saumik Datta

    2013-01-01

    Full Text Available A 42-year-old lady, a known diabetic presented with generalized body ache, severe burning sensation over her lower limbs, loss of weight (approximately 8 kg, loss of appetite, nausea, frequent vomiting, and altered bowel habits without history of fever or pain abdomen. Symmetrical wasting was noted in all limbs with bilateral proximal muscle weakness, particularly of lower limbs. Ankle jerks were absent with symmetrically decreased reflexes. nerve conduction velocity (NCV revealed symmetrical distal axonal and demyelinating type of sensorimotor polyneuropathy. Hematological and gastrointestinal (GI malignancy were excluded. Patient responded to antidepressants.

  14. Ursodeoxycholic acid treatment in a rat model of cancer cachexia

    National Research Council Canada - National Science Library

    Tschirner, Anika; von Haehling, Stephan; Palus, Sandra; Doehner, Wolfram; Anker, Stefan D; Springer, Jochen

    2012-01-01

    .... Ursodeoxycholic acid (UDCA), a bile acid used for centuries in the treatment of liver disease, is known to confer anti-inflammatory and anti-apoptotic effects as well as beneficial effects on mitochondrial integrity and cell signaling...

  15. [Pathomechanism of cachexia in chronic obstructive pulmonary disease].

    Science.gov (United States)

    Jarzab, Jerzy; Chwist-Nowak, Aleksandra; Rozentryt, Piotr; Chwist, Jerzy

    2005-01-01

    Weight loss is a characteristic for advanced chronic obstructive pulmonary disease (COPD), but its mechanism remains unexplained. The decrease of lean body mass is due to a negative energy balance with a noncatabolic hypermetabolic state. Pulmonary inflammation or tissue hypoxia might contribute to it, the decrease in protein content is accompanied by an increase in reactive oxygen forms. Tumor necrosis factor (TNF) has been implicated, other candidates are cytokines IL-1B and IL-6. Activation of apoptosis may be noticed. Pulmonary inflammation and changes in serum leptin may be interrelated. Other hormonal disturbances involve serum IGF-1 level decrease, increase of insulin resistance, raised catecholamine and cortisol levels and other mechanisms which need further investigations. Up to now the attempts undertaken to counteract the observed hormonal changes failed to success.

  16. NUTRITIONAL SUPPORT OF SEPTIC PATIENT WITH INITIAL CACHEXIA

    OpenAIRE

    N. V. Kukhtinova

    2011-01-01

    Enteral nutrition provided to children in critical state is necessary area of pediatrician’s activity in children’s hospital. Enteral nutrition is able to improve the prognosis of the disease significantly along with maintenance of essential functions and treatment of pathologic process, decrease of duration of stay in intensive care department. Proper choice of method and volume of nutritional support and product for medical treatment depending on clinical situation is significant problem. T...

  17. Progressive disseminated histoplasmosis presenting with cachexia and hypercalcemia

    Directory of Open Access Journals (Sweden)

    Khasawneh FA

    2013-02-01

    Full Text Available Faisal A Khasawneh,1 Subhan Ahmed,2 Ruba A Halloush31Section of Infectious Diseases, Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX, 2Section of Nephrology, Department of Internal Medicine, University of Oklahoma, Tulsa, OK, 3Amarillo Pathology Group, Amarillo, TX, USAAbstract: Histoplasmosis is a common endemic mycosis. The majority of infections involving this dimorphic fungus are asymptomatic. Manifestations in symptomatic patients are diverse, ranging from flu-like illness to a more serious disseminated disease. We present here a case of chronic disseminated histoplasmosis mimicking a metastatic cancer. We reviewed the literature for cases of disseminated histoplasmosis presenting with hypercalcemia, focusing particularly on clinical presentation, risk factors predisposing for fungal infection, and outcome. We report a case of a 65-year-old diabetic male who presented with unexplained weight loss and hypercalcemia. Multiple brain space-occupying lesions and bilateral adrenal enlargement were evident on imaging studies. Biopsies showed caseating granulomas with budding yeast, consistent with histoplasmosis. The patient's symptoms resolved after liposomal amphotericin B and itraconazole therapy. Granulomatous diseases, including fungal infections, should be considered alongside malignancies, in patients with similar presentation.Keywords: disseminated histoplasmosis, hypercalcemia

  18. Michelangelo, the Sistine Chapel and the “secret” of cancer cachexia

    African Journals Online (AJOL)

    The clinical journey of chronic diseases, including cancer, renal failure and chronic obstructive pulmonary disease, is frequently characterised by the progressive deterioration of nutritional status, leading to increased morbidity and mortality, and impinges upon quality of life. Diseaseassociated malnutrition is characterised ...

  19. Michelangelo, the Sistine Chapel and the “secret” of cancer cachexia

    African Journals Online (AJOL)

    cells can rely solely on anaerobic glycolysis, in which glucose is converted to pyruvate and then lactate in the cytosol to meet energy needs; this is known as the Pasteur effect. Many invasive cancer cells selectively metabolise glucose to lactic acid in the presence of oxygen, a phenomenon known as the Warburg effect.

  20. Distinct behaviour of sorafenib in experimental cachexia-inducing tumours: the role of STAT3.

    Directory of Open Access Journals (Sweden)

    Míriam Toledo

    Full Text Available The presence of a tumour is very often associated with wasting in the host, affecting both skeletal muscle and adipose tissue. In the present study we used sorafenib, a multi-kinase inhibitor with anti-tumour activity, in order to investigate the effects of chemotherapy on wasting. Three different experimental mouse tumour models were included: C26 colon carcinoma, B16 melanoma and Lewis lung carcinoma (LLC. The results obtained clearly show that sorafenib was effective in reducing tumour growth in LLC and B16 models, while it had no effect on C26. Interestingly, sorafenib treatment reduced the signs of muscle wasting and improved the physical activity in the LLC model and also in the C26, despite the absence of antineoplastic action in the latter. Our results discard a role for IL-6 in the action of sorafenib since the drug did not affect the levels of this cytokine. Conversely, sorafenib seems to act by influencing both STAT3 and ERK activity at muscle level, leading to reduced accumulation of Pax7 and atrogin-1. Sorafenib may interfere with muscle wasting by decreasing the activation of these signal transduction pathways.

  1. Proinflammatory cytokines, nutritional support, and the cachexia syndrome: interactions and therapeutic options.

    Science.gov (United States)

    Moldawer, L L; Copeland, E M

    1997-05-01

    Protein calorie malnutrition remains endemic in hospitalized patients with both acute and chronic inflammation secondary to either cancer, chronic infectious processes, surgical injury, trauma, or burns. For the patients who cannot support themselves by enteral feeding, total parenteral nutrition remains an essential tool to minimize nitrogen losses and replete the depleted patient. However, in patients with active inflammation, nitrogen retention and lean tissue accretion are often impaired during total parenteral nutrition. Production of humoral factors, including proinflammatory cytokines, regulates many of the anabolic and catabolic processes that accompany inflammation. The investigators' experience with total parenteral nutrition and proinflammatory cytokines is reviewed. Cytokines such as interleukin-1, tumor necrosis factor-alpha, and, in particular, interleukin-6 appear to play central roles in both the loss of skeletal muscle protein and the initiation of the acute phase response to inflammation, as well as in modulating the utilization of exogenously administered nutrients. Although innovative second- and third-generation nutritional formulations for the acutely ill patient may represent one approach for improving the effectiveness of total parenteral nutrition, understanding the humoral response to inflammation and modifying cytokine actions pharmacologically may prove equally effective in improving the utility of exogenously administered nutrients. Future studies need to determine whether the effectiveness of exogenously administered nutrients in the patient with inflammation can be improved by efforts to modulate the proinflammatory cytokine response through cytokine inhibitors or antagonists.

  2. Ghrelin improves body weight loss and skeletal muscle catabolism associated with angiotensin II-induced cachexia in mice.

    Science.gov (United States)

    Sugiyama, Masako; Yamaki, Akira; Furuya, Mayumi; Inomata, Norio; Minamitake, Yoshiharu; Ohsuye, Kazuhiro; Kangawa, Kenji

    2012-10-10

    Ghrelin is a gastric peptide that regulates energy homeostasis. Angiotensin II (Ang II) is known to induce body weight loss and skeletal muscle catabolism through the ubiquitin-proteasome pathway. In this study, we investigated the effects of ghrelin on body weight and muscle catabolism in mice treated with Ang II. The continuous subcutaneous administration of Ang II to mice for 6 days resulted in cardiac hypertrophy and significant decreases in body weight gain, food intake, food efficiency, lean mass, and fat mass. In the gastrocnemius muscles of Ang II-treated mice, the levels of insulin-like growth factor 1 (IGF-1) were decreased, and the levels of mRNA expression of catabolic factors were increased. Although the repeated subcutaneous injections of ghrelin (1.0mg/kg, twice daily for 5 days) did not affect cardiac hypertrophy, they resulted in significant body weight gains and improved food efficiencies and tended to increase both lean and fat mass in Ang II-treated mice. Ghrelin also ameliorated the decreased IGF-1 levels and the increased mRNA expression levels of catabolic factors in the skeletal muscle. IGF-1 mRNA levels in the skeletal muscle significantly decreased 24h after Ang II infusion, and this was reversed by two subcutaneous injections of ghrelin. In C2C12-derived myocytes, the dexamethasone-induced mRNA expression of atrogin-1 was decreased by IGF-1 but not by ghrelin. In conclusion, we demonstrated that ghrelin improved body weight loss and skeletal muscle catabolism in mice treated with Ang II, possibly through the early restoration of IGF-1 mRNA in the skeletal muscle and the amelioration of nutritional status. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Novel intervention with acupuncture for anorexia and cachexia in patients with gastrointestinal tract cancers: a feasibility study.

    Science.gov (United States)

    Yoon, Saunjoo L; Grundmann, Oliver; Williams, Joseph J; Carriere, Gwen

    2015-03-01

    To investigate the feasibility of using acupuncture as a complementary intervention to existing treatments and to evaluate the efficacy of acupuncture in improving appetite and slowing weight loss with patients with gastrointestinal (GI) tract cancers. 
 One-group pre- and postintervention feasibility study. 
 Outpatient clinic for patients with cancer and a community setting, both in Florida. 
 A convenience sample of seven adults with GI cancer.
 Eight acupuncture sessions were provided during eight weeks. Data were collected using the visual analog scale (VAS) for appetite, Simplified Nutritional Appetite Questionnaire (SNAQ), Karnofsky Performance Status, and bioelectrical impedance analysis. 
 Appetite, weight, attrition rate.
 Seven patients with a mean age of 61 years completed the intervention. Acupuncture was well accepted, feasible, and safe without any reported side effects. Appetite showed improvement, with an average score of 3.04 on the VAS and 4.14 on SNAQ compared to the preintervention scores. The average weight loss was 1.32% compared to the baseline during an eight-week period. 
 The acupuncture intervention was feasible and indicated positive outcomes. Because of the small sample size and lack of a control group, statistical significance of effectiveness was not determined. Acupuncture seemed to improve appetite and slow weight loss in patients with GI cancers, so additional studies with a larger sample size and a variety of cancers are warranted. 
 Oncology nurses are uniquely able to equip patients with information about complementary therapy modalities, such as acupuncture, which is a promising way to improve appetite and slow weight loss in patients with GI cancers.


  4. Daily physical-rest activities in relation to nutritional state, metabolism, and quality of life in cancer patients with progressive cachexia.

    Science.gov (United States)

    Fouladiun, Marita; Körner, Ulla; Gunnebo, Lena; Sixt-Ammilon, Petra; Bosaeus, Ingvar; Lundholm, Kent

    2007-11-01

    To evaluate daily physical-rest activities in cancer patients losing weight in relation to disease progression. Physical activity-rest rhythms were measured (ActiGraph, armband sensor from BodyMedia) in relation to body composition (dual-energy X-ray absorptiometry), energy metabolism, exercise capacity (walking test), and self-scored quality of life (SF-36, Hospital Anxiety and Depression Scale) in weight-losing outpatients with systemic cancer (71 +/- 2 years, n = 53). Well-nourished, age-matched, and previously hospitalized non-cancer patients served as controls (74 +/- 4 years, n = 8). Middle-aged healthy individuals were used as reference subjects (49 +/- 5 years, n = 23). Quality of life was globally reduced in patients with cancer (P < 0.01), accompanied by significantly reduced spontaneous physical activity during both weekdays and weekends compared with reference subjects (P < 0.01). Spontaneous physical activity declined over time during follow-up in patients with cancer (P < 0.05). However, overall physical activity and the extent of sleep and bed-rest activities did not differ between patients with cancer and age-matched non-cancer patients. Spontaneous physical activity correlated weakly with maximum exercise capacity in univariate analysis (r = 0.41, P < 0.01). Multivariate analysis showed that spontaneous physical activity was related to weight loss, blood hemoglobin concentration, C-reactive protein, and to subjectively scored items of physical functioning and bodily pain (SF-36; P < 0.05-0.004). Anxiety and depression were not related to spontaneous physical activity. Patient survival was predicted only by weight loss and serum albumin levels (P < 0.01), although there was no such prediction for spontaneous physical activity. Daily physical-rest activities represent variables which probably reflect complex mental physiologic and metabolic interactions. Thus, activity-rest monitoring provides a new dimension in the evaluation of medical and drug interventions during palliative treatment of patients with cancer.

  5. Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants.

    OpenAIRE

    Buck, M; Chojkier, M.

    1996-01-01

    Muscle wasting is a critical feature of patients afflicted by AIDS or cancer. In a murine model of muscle wasting, tumor necrosis factor alpha (TNF alpha) induces oxidative stress and nitric oxide synthase (NOS) in skeletal muscle, leading to decreased myosin creatinine phosphokinase (MCK) expression and binding activities. The impaired MCK-E box binding activities resulted from abnormal myogenin-Jun-D complexes, and were normalized by the addition of Jun-D, dithiothreitol or Ref-1, a nuclear...

  6. Nutrition in Head and Neck Cancer Patients

    OpenAIRE

    Varkey, Prashanth; Tang, Wen-Ruay; Tan, Ngian Chye

    2010-01-01

    Anorexia and cachexia frequently complicate the late stages of malignancy and can be a prominent feature of early disease. The resulting weight loss significantly affects the morbidity and mortality of the cancer patient. A fundamental understanding of nutrition and the pathophysiology of cancer cachexia will aid in diligent treatment decisions to achieve optimal results. The pathophysiology of cancer cachexia is discussed, together with methods of nutritional assessment, nutritional requirem...

  7. Causas e impacto clínico de la desnutrición y caquexia en el paciente oncológico Causes and impact of hyponutrition and cachexia in the oncologic patient

    OpenAIRE

    P. P. García-Luna; J. Parejo Campos; Pereira Cunill, J. L.

    2006-01-01

    La expresión máxima de desnutrición en el cáncer es la caquexia tumoral, que será responsable directa o indirecta de la muerte en un tercio de los pacientes con cáncer. Las causas de desnutrición en el cáncer están relacionadas con el tumor, con el paciente o con los tratamientos y de forma resumida podemos diferenciar 4 grandes mecanismos por los que puede aparecer desnutrición en el paciente canceroso: • Escaso aporte de energía y nutrientes. • Alteraciones de la digestión y/o abs...

  8. Association between body image dissatisfaction and weight loss among patients with advanced cancer and their caregivers: a preliminary report

    National Research Council Canada - National Science Library

    Rhondali, Wadih; Chisholm, Gary B; Daneshmand, Maryam; Allo, Julio; Kang, Duck-Hee; Filbet, Marilene; Hui, David; Fingeret, Michelle Cororve; Bruera, Eduardo

    2013-01-01

    No prospective studies have dealt with the impact of cachexia-related weight loss on patients' body image as well as the impact of patients' body image changes on the level of patient and family distress...

  9. The White, the Brite and the Brown

    DEFF Research Database (Denmark)

    Pedersen, Lone Møller

    cyclooxygenases (COXs) in energy homeostasis in obesity, but also in the opposite situation during energy deficiency as seen in cancer cachexia. The first study investigates the effects of polyunsaturated fatty acids (PUFAs) of the n-6 class in obesity development. Depending on the background diet, being either...... the hyperinflammatory state and the increased energy expenditure observed in cancer-associated cachexia. Screening a cohort of cancer cell lines we have picked a low and a high PGE2 secreting cell line for subcutaneous implantation into nude mice. Initial analysis has shown animals implanted with the high PGE2...... secreting cell line to develop cachexia as assessed by decreased mass of both adipose tissue and skeletal muscle, the hallmarks of the wasting syndrome seen in cachexia. Further analysis is needed to explore the mechanisms involved, but very preliminary data could point to a scenario partly dependent...

  10. Wasting in chronic kidney disease

    National Research Council Canada - National Science Library

    Mak, Robert H; Ikizler, Alp T; Kovesdy, Csaba P; Raj, Dominic S; Stenvinkel, Peter; Kalantar-Zadeh, Kamyar

    2011-01-01

    Wasting/cachexia is prevalent among patients with chronic kidney disease (CKD). It is to be distinguished from malnutrition, which is defined as the consequence of insufficient food intake or an improper diet...

  11. Cannabinoid CB1 receptor-interacting proteins: novel targets for central nervous system drug discovery?

    National Research Council Canada - National Science Library

    Smith, Tricia H; Sim-Selley, Laura J; Selley, Dana E

    2010-01-01

    ...), including CB1 and CB2 receptors. The CB1 receptor is the major cannabinoid receptor in the central nervous system and has gained increasing interest as a target for drug discovery for treatment of nausea, cachexia, obesity, pain...

  12. Calorie or Carbohydrate Restriction? The Ketogenic Diet as Another Option for Supportive Cancer Treatment

    OpenAIRE

    Klement, Rainer J.

    2013-01-01

    The author agrees with Champ et al. that calorie reduction (CR) is a good supportive intervention for patients undergoing radiotherapy or chemotherapy. However, for those with cachexia or for those who are at risk for cachexia, CR may be problematic. Additionally, less food consumed means fewer nutrients. For these patients, the author suggests the addition of the ketogenic diet, which could be designed to include high-quality foods and could be combined with anticancer neutraceuticals.

  13. Relationships between oxycodone pharmacokinetics, central symptoms, and serum interleukin-6 in cachectic cancer patients.

    Science.gov (United States)

    Sato, Hikaru; Naito, Takafumi; Ishida, Takuya; Kawakami, Junichi

    2016-12-01

    Elevated serum proinflammatory cytokines are associated with the reduction of cytochrome P450 enzyme (CYP) activity. This study aimed to evaluate the oxycodone pharmacokinetics, central symptoms, and serum proinflammatory cytokines based on cachexia stage in cancer patients. Forty-seven cancer patients receiving extended-release oxycodone were enrolled. Predose plasma concentrations of oxycodone and its metabolites were normalized with the daily dose and body weight. The central symptoms and serum level of proinflammatory cytokines were investigated at each cachexia stage. The plasma concentrations of oxycodone in patients with cachexia and refractory cachexia were significantly higher than that in patients with precachexia. The metabolic ratio to noroxycodone in patients with cachexia was significantly lower than that in patients with precachexia. The patients with a higher cachexia stage had a higher serum level of interleukin-6 (IL-6), but not tumor necrosis factor-α and interleukin-1β. The serum IL-6 level was correlated with the plasma concentration of oxycodone and inversely with the metabolic ratio to noroxycodone. The incidence of somnolence was not associated with the plasma oxycodone concentration. In contrast, the cachexia stage and its associated serum IL-6 level were correlated with the incidence of somnolence. Cancer cachexia raised the plasma exposure of oxycodone through the reduction of CYP3A metabolic pathway. The reduction of CYP3A in cachectic cancer patients was associated with an elevation of serum IL-6. Although cachectic cancer patients with higher serum IL-6 levels had the symptom of somnolence, the alterations in oxycodone pharmacokinetics were not related to the incidence of symptom.

  14. The Effect of Special Operations Training on Testosterone, Lean Body Mass, and Strength and the Potential for Therapeutic Testosterone Replacement: A Review of the Literature

    Science.gov (United States)

    2016-07-01

    and muscle function during SOF training or sustained operations.  15. SUBJECT TERMS Androgenic, anabolic, cachexia, fatigue 16. SECURITY...Testosterone. Both testosterone and AAS have been used therapeutically to prevent cachexia, muscle wasting, and fatigue in patients living with HIV and...stopped. JAMA . 1992; 267(3):397-399. 26. Griggs RC, Kingston W, Jozefowicz RF, Herr BE, Forbes G, Halliday D. Effect of testosterone on muscle mass

  15. New observations on chronic intoxication by very small doses of sodium fluosilicate

    Energy Technology Data Exchange (ETDEWEB)

    Cristiani, H.; Chausse, P.

    1927-01-01

    It was determined that daily doses of approximately 0.1 of the lethal dose of sodium fluoride produced a fluoric cachexia in guinea pigs which caused the death of the animals in 2 or 3 months. Animals which were given 0.02 of the lethal dose of sodium fluoride were apparently in good health for a period of 10 months. However, after two or three years cachexia was likely to appear.

  16. Hypothalamic lipid metabolism and the control of food intake

    OpenAIRE

    Arisha, Ahmed Hamed

    2016-01-01

    Homeostatic regulation of energy balance is a precise tool concerned with maintaining a stable balance between energy intake and expenditure. Failure in the regulation of this physiological process gives rise to some disorders that are now considered public health problems with their reported increase in prevalence rate such as obesity and cachexia. obesity is caused by a chronic rise in energy consumption while cachexia results from a long-standing increase expended energy. Brown adipose tis...

  17. Balanço entre ácidos graxos ômega-3 e 6 na resposta inflamatória em pacientes com câncer e caquexia Omega-3 and 6 fatty acids balance in inflammatory response in patients with cancer and cachexia

    Directory of Open Access Journals (Sweden)

    Adriana Garófolo

    2006-10-01

    Full Text Available O emagrecimento, associado à perda de massa magra, é um fenômeno observado com freqüência em pacientes com câncer. Tal condição predispõe o paciente ao maior risco de infecções, pior resposta aos tratamentos implantados e, como conseqüência, desfavorece o prognóstico de cura. Além disso, a desnutrição também está associada à pior qualidade de vida. Dessa forma, algumas terapias têm sido propostas na tentativa de reverter o catabolismo, por meio da atenuação da resposta inflamatória, observado em grande porcentagem de pacientes com câncer e caquexia. Entre elas, a suplementação com ácidos graxos da família ômega-3 pode representar uma estratégia na redução da formação de citocinas pró-inflamatórias, favorecendo a tolerância metabólica dos substratos energéticos e atenuando o catabolismo protéico, com o intuito de melhorar o prognóstico de cura de pacientes com câncer. Entretanto, os estudos mostram alguns resultados conflitantes da suplementação com ômega-3 na resposta imunológica. Por outro lado, em pacientes com câncer, os ensaios clínicos mostraram atenuar a resposta inflamatória e melhorar o estado nutricional. O objetivo deste artigo é realizar uma revisão criteriosa do assunto.Emaciation and loss of lean body mass is a frequent phenomenon observed in cancer patients. This condition leads to infection risk and a poor response to treatment, thus reducing the chances of cure. Furthermore, malnutrition is also associated with a poor quality of life. Therefore, therapies have been proposed in attempt to revert the catabolism observed in most of these patients by attenuating the inflammatory response. Among them, omega-3 fatty acid supplementation may be a strategy to reduce the production of pro-inflammatory cytokines and improve metabolic substrate tolerance, decreasing protein catabolism in order to ameliorate the prognosis of cure in cancer patients. However, studies demonstrate some conflicting results of ômega-3 supplementation on immune response. On the other hand, clinical trials in cancer patients demonstrate that the inflammatory response decreases and the nutritional status improves. The aim of this paper is to elaborate a strict review of the subject.

  18. Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer.

    Science.gov (United States)

    Stene, Guro B; Helbostad, Jorunn L; Amundsen, Tore; Sørhaug, Sveinung; Hjelde, Harald; Kaasa, Stein; Grønberg, Bjørn H

    2015-03-01

    Sarcopenia is a defining feature of cancer cachexia associated with physical decline, poor quality of life and poor prognosis. Thus, maintaining muscle mass is an important aim of cachexia treatment. Many patients at risk for developing cachexia or with cachexia experience side effects of chemotherapy that might aggravate the development of cachexia. However, achieving tumor control might reverse the catabolic processes causing cachexia. There is limited knowledge about muscle mass changes during chemotherapy or whether changes in muscle mass are associated with response to chemotherapy. In this pilot study, patients with advanced non-small cell lung cancer (NSCLC) receiving three courses of palliative chemotherapy were analyzed. Muscle mass was measured as skeletal muscle cross sectional area (SMCA) at the level of the third lumbar vertebrae using CT images taken before and after chemotherapy. In total 35 patients, 48% women, mean age 67 years (range 56-86), participated; 83% had stage IV disease and 71% were sarcopenic at baseline. Mean reduction in SMCA from pre- to post-chemotherapy was 4.6 cm2 (CI 95% -7.3--1.9; pmuscle mass. Sixteen patients remained stable or gained SMCA. Of these, 14 (56%) responded to chemotherapy, while two progressed (p=0.071). Maintaining or gaining SMCA resulted in longer median overall survival (loss: 5.8 months, stable/gain: 10.7 months; p=0.073). Stage of disease (p=0.003), treatment regimen (p=0.023), response to chemotherapy (p=0.007) and SMCA change (p=0.040), but not sarcopenia at baseline, were significant prognostic factors in the multivariate survival analyses. Almost half of the patients had stable or increased muscle mass during chemotherapy without receiving any cachexia treatment. Nearly all of these patients responded to the chemotherapy. Increase in muscle mass, but not sarcopenia at baseline, was a significant prognostic factor.

  19. Current concepts in cancer: effects of cancer and cancer treatment on the nutrition of the host

    Energy Technology Data Exchange (ETDEWEB)

    Costa, G.; Donaldson, S.S.

    1979-06-28

    The growth of cancer in man leads to destruction of tissues and alterations of functions. The consequences of this process, culminating in overt cachexia and death, are so varied that cancer has replaced syphilis as the great imitator. Many of the manifestations of cachexia (weakness, anorexia, depletion and translocation of host component, and loss of immunocompetence) resemble malnutrition and are accountable for, in many patients, by poor nutritional intake, neoplastic invasion of the gastrointestinal tract or creation by the tumor of abnormal routes through which nutrients can be lost. The development of cachexia, nevertheless, bears no simple relation to caloric intake, tumor burden, tumor cell type or anatomic site of involvement. Indeed, it has long been apparent that, in many patients succumbing to cancer, if the same lesions were composed of scar tissue rather than neoplastic cells, the affected individuals might not only be alive but in reasonably good health. Distant metabolic effects of cancers have therefore come into focus, are well documented and are known collectively as paraneoplastic syndromes. They imply release by the tumor of chemically identifiable toxic mediators. Recently, a third mechanism has been recognized as an important determinant of cachexia and malnutrition: cancer treatment. As our tools have become more powerful and our philosophies more agressive,the effects of therapy on normal cell populations have become visible. The present paper discusses the most important manifestations of cachexia that resemble malnutrition. Technics of nutritional assessment and intervention that have proved successful in patients with cancer are also briefly discussed.

  20. A differential pattern of gene expression in skeletal muscle of tumor-bearing rats reveals dysregulation of excitation–contraction coupling together with additional muscle alterations.

    Science.gov (United States)

    Fontes-Oliveira, Cibely Cristine; Busquets, Sílvia; Fuster, Gemma; Ametller, Elisabet; Figueras, Maite; Olivan, Mireia; Toledo, Míriam; López-Soriano, Francisco J; Qu, Xiaoyan; Demuth, Jeffrey; Stevens, Paula; Varbanov, Alex; Wang, Feng; Isfort, Robert J; Argilés, Josep M

    2014-02-01

    Cachexia is a wasting condition that manifests in several types of cancer. The main characteristic of this condition is a profound loss of muscle mass. By using a microarray system, expression of several hundred genes was screened in skeletal muscle of rats bearing a cachexia-inducing tumor, the AH-130 Yoshida ascites hepatoma. This model induced a strong decrease in muscle mass in the tumor-bearing animals, as compared with their healthy counterparts. The results show important differences in gene expression in EDL skeletal muscle between tumor-bearing animals with cachexia and control animals. The differences observed pertain to genes related to intracellular calcium homeostasis and genes involved in the control of mitochondrial oxidative phosphorylation and protein turnover, both at the level of protein synthesis and proteolysis. Assessment of these differences may be a useful tool for the design of novel therapeutic strategies to fight this devastating syndrome.

  1. Uveitis associated to the infection by Leishmania chagasi in dog from the Olinda city, Pernambuco, Brazil

    Directory of Open Access Journals (Sweden)

    Brito Fábio Luiz da Cunha

    2004-01-01

    Full Text Available Among the parasitic diseases, Canine Visceral Leishmaniasis (CVL is included in the systemic illnesses of chronic evolution that attack men and dogs, presenting varied clinical manifestations as cachexia, dermatologic lesions, peripheral lymphadenopathies, besides the ocular lesions. This work report the case of a dog clinically suspected of having CVL, presenting skin lesions, cachexia, gryphosis, and ocular signs of uveitis. The parasitological diagnosis was accomplished for Canine Leishmaniasis through the visualization of amastigote forms of Leishmania chagasi in smears of bone marrow fluid aspirate, of non-lesioned, and lesioned skin. Alterations in the ocular structures are characterized mainly by mononuclear-plasmocitic infiltrate.

  2. [A case report of the difficulty treating an endstage oncologic ENT patient with parenteral nutrition].

    Science.gov (United States)

    Uxa-Benold, Ulrike; Simanek, Ralph; Henry, Annette; Weixler, Dietmar; Geissler, Klaus

    2014-05-01

    The occurrence of cachexia at the end of life of patients suffering from cancer is a common seen problem. Within the last years new definitions, diagnostic criteria and classification systems of cachexia have been developed to improve the clinical practice. Still therapeutic interventions are limited; the role of parenteral nutrition (PN) remains controversial. PN cannot be generally recommended in patients with incurable malignancies, not even in ill-nourished patients with inadequate oral or enteral nutrition due to a changed metabolism. Treating a cachectic endstage patient suffering from head-neck-cancer we were faced with different problems.

  3. Disruption of pro-oxidant and antioxidant systems with elevated expression of the ubiquitin proteosome system in the cachectic heart muscle of nude mice.

    Science.gov (United States)

    Hinch, E C A; Sullivan-Gunn, M J; Vaughan, V C; McGlynn, M A; Lewandowski, Paul A

    2013-12-01

    Current research into the mechanisms of organ atrophy associated with cancer cachexia have centred on the loss of skeletal muscle, as it is one of the most profound physical changes of the disease. However, many patients with cancer cachexia also experience significant atrophy of the heart. The mechanisms causing cardiac tissue wastage in cancer cachexia are largely unknown. However, it is believed to involve a number of molecular interactions between the tumour and host. Increased levels of oxidative stress have been found in cancer cachectic skeletal muscle and has been linked to the activation of the ubiquitin proteosome system (UPS). The aim of the current study was to examine the role of oxidative stress and the UPS in the hearts of mice with cancer cachexia. Oxidative damage to DNA (8-OH-2dG), mRNA levels of the ROS-producing enzymes NADPH oxidase (NOX), and xanthine oxidase (XDH), the antioxidant enzyme superoxide dismutase (SOD) and key components of the UPS was measured in the heart of mice with cancer cachexia. Protein expression levels of NOX enzyme subunits and SOD enzyme activity was also measured in the same heart samples. 8-OH-2dG levels were 1.5-fold higher in the heart of mice with cancer cachexia, and this was associated with a 1.7-fold lower level of NOX2 mRNA and twofold higher XDH mRNA in the same hearts. Cancer cachexia was also associated with a 1.5-fold lower level of SOD activity in the heart. Accompanying these pro- and antioxidant differences was a significantly higher level of mRNA for the key UPS elements MURF-1 (4.3=fold) and MAFbx (3.8-fold) in the hearts of mice with cancer cachexia. The current study demonstrated that cardiac atrophy of cachectic mice is associated with oxidative damage to DNA in the myocardium. The higher levels of XDH mRNA in cachectic hearts suggest that xanthine oxidase may have an important role to play in producing oxidative stress. It appears that the combination of higher XDH expression and lower SOD enzyme

  4. A previously healthy 11-year-old girl with behavioural disturbances, desquamation of the skin and loss of teeth.

    NARCIS (Netherlands)

    Linde, A.A. van der; Lewiszong-Rutjens, C.A.; Verrips, A.; Gerrits, G.P.

    2009-01-01

    An 11-year-old girl was admitted with backpain, weight loss, fatigue and behavioural disturbances, starting seven weeks before admission. Physical examination showed acrodynia, tremor, cachexia, hypertension and extensive gingival ulceration. Routine laboratory tests were normal, except for a CRP of

  5. Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice

    NARCIS (Netherlands)

    Norren, van K.; Kegler, D.; Argiles, J.M.; Luiking, Y.; Gorselink, M.; Laviano, A.; Arts, K.; Faber, J.; Jansen, H.; Beek, van der E.M.; Helvoort, van A.

    2009-01-01

    Cancer cachexia is characterised by metabolic alterations leading to loss of adipose tissue and lean body mass and directly compromises physical performance and the quality of life of cancer patients. In a murine cancer cachectic model, the effects of dietary supplementation with a specific

  6. Vulnerable long-term psychiatric inpatients need screening for ...

    African Journals Online (AJOL)

    Conclusion: Increased screening should be conducted for older underweight male patients (for chronic respiratory or infectious diseases that might cause cachexia) and of patients with cognitive disorders or who have fallen (for treatable risk factors for falling and preventative measures). More patients should be referred for ...

  7. Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice

    NARCIS (Netherlands)

    Peters, S.J.; Helvoort, van A.; Kegler, D.; Argiles, J.M.; Luiking, Y.C.; Laviano, A.; Bergenhenegouwen, van J.; Deutz, N.E.P.; Haagsman, H.P.; Gorselink, M.; Norren, van K.

    2011-01-01

    Cancer cachexia, which is characterized by muscle wasting, is associated with increased morbidity and mortality. Because muscle protein synthesis may be increased and protein breakdown reduced by leucine supplementation, we used the C26 tumor-bearing cachectic mouse model to assess the effects of

  8. Identification of possible genetic polymorphisms involved in cancer ...

    Indian Academy of Sciences (India)

    Fat mass and obesity associated (FTO) is thought to play a role in energy homeostasis but its exact function is unknown. Genetic variants encoding the proteins discussed above may play a role in the development of cachexia and are listed in table 15 of electronic supplementary material. Analysis of results. Out of 184 ...

  9. TUMOR-GROWTH DELAY BY LASER-GENERATED SHOCK-WAVES

    NARCIS (Netherlands)

    de Reijke, T. M.; Schamhart, D. H.; Kurth, K. H.; Löwik, C. W.; Donkers, L. H.; Sterenborg, H. J.

    1994-01-01

    The antiproliferative effect of laser-generated shock waves (L-SW) was investigated on a human renal cell carcinoma, RC-8, grown subcutaneously in the nu/nu mouse. The RC-8 is characterized by the syndrome of humoral hypercalcemia of malignancy (HHM) associated with profound cachexia, increase of

  10. Identification of possible genetic polymorphisms involved in cancer ...

    Indian Academy of Sciences (India)

    A systematic search of Medline and EmBase databases, covering 1986–2008 was performed for potential candidate genes/genetic polymorphisms relating to cancer cachexia. Related genes were then identified using pathway functional analysis software. All candidate genes were reviewed for functional polymorphisms or ...

  11. Pyometra in a Great Dane: A Clinical Case Report

    Directory of Open Access Journals (Sweden)

    Malik Abu Rafee

    2015-04-01

    Full Text Available A 4-year-old Great Dane was admitted with continuous sanguino-purulent vaginal discharge, distended abdomen, and cachexia. The dog was clinically diagnosed with pyometra and successfully cured by ovario-hysterectomy. This is the first case report of pyometra seen in as Great Dane in Bareilly, India.

  12. [Gelatinous transformation of the bone marrow. Apropos of 3 cases].

    Science.gov (United States)

    Feugier, P; Guerci, A; Boman, F; Stockemer, V; Lederlin, P

    1995-01-01

    Gelatinous transformation of the bone marrow is a rare histological lesion usually associated with cachexia. The authors report three new cases, two in anorexia nervosa and the third in Hodgkin disease. A review of the literature underlines association with marrow cell necrosis and provides the most frequent etiologies. Pathogenesis of gelatinous transformation remains unclear and her prognostic depends on etiology.

  13. Protein calorie malnutrition, nutritional intervention and personalized cancer care.

    Science.gov (United States)

    Gangadharan, Anju; Choi, Sung Eun; Hassan, Ahmed; Ayoub, Nehad M; Durante, Gina; Balwani, Sakshi; Kim, Young Hee; Pecora, Andrew; Goy, Andre; Suh, K Stephen

    2017-04-04

    Cancer patients often experience weight loss caused by protein calorie malnutrition (PCM) during the course of the disease or treatment. PCM is expressed as severe if the patient has two or more of the following characteristics: obvious significant muscle wasting, loss of subcutaneous fat; nutritional intake of 2% in 1 week, 5% in 1 month, or 7.5% in 3 months. Cancer anorexia-cachexia syndrome (CACS) is a multifactorial condition of advanced PCM associated with underlying illness (in this case cancer) and is characterized by loss of muscle with or without loss of fat mass. Cachexia is defined as weight loss of more than 5% of body weight in 12 months or less in the presence of chronic disease. Hence with a chronic illness on board even a small amount of weight loss can open the door to cachexia. These nutritional challenges can lead to severe morbidity and mortality in cancer patients. In the clinic, the application of personalized medicine and the ability to withstand the toxic effects of anti-cancer therapies can be optimized when the patient is in nutritional homeostasis and is free of anorexia and cachexia. Routine assessment of nutritional status and appropriate intervention are essential components of the effort to alleviate effects of malnutrition on quality of life and survival of patients.

  14. Mammary tumorigenesis causes bone loss and dietary selenium supplementation does not affect such bone loss in male MMTV-PyMT mice

    Science.gov (United States)

    Cancer progression is accompanied by wasting that eventually results in cachexia characterized by significant weight loss and multi-organ functional failures. Limited clinical trials indicate that bone is adversely affected by cancer-associated wasting. To determine the effects of breast cancer on...

  15. ISSN 2073-9990 East Cent. Afr. J. surg. (Online) 33

    African Journals Online (AJOL)

    Hp 630 Dual Core

    Publication COSECSA/ASEA -East and Central African Journal of Surgery. .... dietary factors like zinc, selenium, and folate deficiencies increase the risk of oesophageal ... sever progressive dysphagia and cachexia of more than six months after .... and 4.4 for esophageal and gastric cardia adenocarcinoma, respectively).

  16. Disease: H01479 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available , such as fever, fatigue, anorexia, anemia, and cachexia. Castleman disease is unique in that dysregulated secretion of interleukin-6... ... Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease. ... JOURNAL ... J Clin Oncol 28:3701-8 (2010) DOI:10.1200/JCO.2009.27.2377

  17. A case report of visceral leishmaniasis in red fox ( Vulpes vulpes ...

    African Journals Online (AJOL)

    A survey of 52 red foxes, a single two year old male weighing about 6 kg showed clinical signs including hair loss, impotence, local or general lymphadenopathy, keratitis, hepatosplenomegaly, lymphadenopathy, hair shedding, dermal lesions, onychogriposis and cachexia. The studied fox IFA titer was larger or equal to ...

  18. Exercise as a Time-conditioning Effector in Chronic Disease: a Complementary Treatment Strategy

    Directory of Open Access Journals (Sweden)

    Luis F. B. P. Costa Rosa

    2004-01-01

    Full Text Available Exercise has been widely believed to be a preventive and therapeutic aid in the treatment of various pathophysiological conditions such as cardiovascular disease and cancer. A common problem associated with such pathologies is cachexia, characterized by progressive weight loss and depletion of lean and fat body mass, and is linked to poor prognosis. As this syndrome comprises changes in many physiological systems, it is tempting to assume that the modulation of the psychoneuroimmunoendocrine axis could attenuate or even prevent cachexia progression in cancer patients. Cancer cachexia is characterized by a disruption in the rhythmic secretion of melatonin, an important time-conditioning effector. This hormone, secreted by the pineal gland, transmits circadian and seasonal information to all organs and cells of the body, synchronizing the organism with the photoperiod. Considering that exercise modulates the immune response through at least two different mechanisms—metabolic and neuroendocrine—we propose that the adoption of a regular exercise program as a complementary strategy in the treatment of cancer patients, with the exercise bouts regularly performed at the same time of the day, will ameliorate cachexia symptoms and increase survival and quality of life.

  19. Locomotion and muscle mass measures in a murine model of collagen-induced arthritis

    NARCIS (Netherlands)

    Hartog, A.; Hulsman, J.; Garssen, J.

    2009-01-01

    Background: Rheumatoid arthritis (RA) is characterized by chronic poly-arthritis, synovial hyperplasia, erosive synovitis, progressive cartilage and bone destruction accompanied by a loss of body cell mass. This loss of cell mass, known as rheumatoid cachexia, predominates in the skeletal muscle and

  20. Vulnerable long-term psychiatric in- patients need screening for ...

    African Journals Online (AJOL)

    guidelines for their treatment: heart failure, vitamin D, falls, ... to respiratory tract infections and lower body weight); patients with cognitive disorders (prone to any injury, especially accidents ... conducted for older underweight male patients (for chronic respiratory or infectious diseases that might cause cachexia) and of.

  1. Pharmacokinetics of Antibiotics in Sub-Saharan African Patient Populations: A Systematic Review

    NARCIS (Netherlands)

    Bos, Jeannet C.; van Hest, Reinier M.; Prins, Jan M.

    2017-01-01

    Background: In sub-Saharan Africa (SSA), severe febrile illness accounts for a large majority of medical admissions. SSA patients may also suffer from cachexia and organ dysfunction resulting from tuberculosis, hepatitis B, and hypertension. It is hard to tell how these conditions influence the

  2. Sarcopenia is associated with an increased inflammatory response to surgery in colorectal cancer

    NARCIS (Netherlands)

    Reisinger, Kostan W.; Derikx, Joep P. M.; van Vugt, Jeroen L. A.; Von Meyenfeldt, Maarten F.; Hulsewé, Karel W.; Olde Damink, Steven W. M.; Stoot, Jan H. M. B.; Poeze, Martijn

    2016-01-01

    Background & aims: Sarcopenia in gastrointestinal cancer has been associated with poor clinical outcome after surgery. The effect of low muscle mass on the inflammatory response to surgery has not been investigated, however skeletal muscle wasting in the context of cachexia is associated with a

  3. Atypical extensive genital ulcer in full blown aids with slim disease ...

    African Journals Online (AJOL)

    Background: Atypical and exceptional clinical presentation of full blown AIDS may be observed in sub-Saharan Africa. We report herein the case of a Central African 37-year-old male patient presented with full blown AIDS, a typical picture of slim disease with marked cachexia and wasting faces. In addition, the patient was ...

  4. Nasogastric tube feeding in children with cancer: The effect of two different formulas on weight, body composition, and serum protein concentrations

    NARCIS (Netherlands)

    Broeder, den E.; Lippens, L.J.J.; Hof, van 't M.A.; Tolboom, J.J.M.; Sengers, R.C.A.; Berg, van den A.M.J.; Staveren, van W.A.

    2000-01-01

    Background: Treatment of cancer cachexia partly involves the administration of adequate amounts of energy. The aim of this study was to assess the tolerance and efficacy of two equal volumes of tube feeding, one with a standard (1 kcal/mL) and one with a high energy density (1.5 kcal/mL), during the

  5. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice

    Science.gov (United States)

    Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghreli...

  6. A randomized study of the effect of fish oil on n-3 fatty acid incorporation and nutritional status in lung cancer patients

    DEFF Research Database (Denmark)

    Andersen, Jens Rikardt; Dannerfjord, Stina Hjerrild; Nørgaard, Michael

    2015-01-01

    Long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFA) have been proposed to have beneficial effect on cancer cachexia. The aims of the present study were to a) determine the incorporation of n-3 LCPUFA in erythrocytes (RBC) as a measurement of compliance to fish oil (FO)-supplement in lung cancer...

  7. June 2002 EAST AFRICAN MEDICAL JOURNAL 3ll

    African Journals Online (AJOL)

    2002-06-01

    Jun 1, 2002 ... cachexia. Additionally, economic and local constraints have limited patients' only therapeutic option to surgery. The reports of results by Orringer and. Sloan(2) and others(3-6) suggested that trans-hiatal oesophagectomy (THE) might offer these debilitated patients palliation at a reduced morbidity and ...

  8. Prevalence of HIV seropositivity in paediatric surgical patients at the ...

    African Journals Online (AJOL)

    ... a hernia and severe cachexia. Conclusion: Prevalence of HIV seropositivity is very low among paediatric surgical patients at NAUTH. Routine screening of patients is not necessary and should not form part of the policy. We recommend routine counselling of parents and provision of facilities for precautionary measures as ...

  9. Health SA Gesondheid - Vol 13, No 2 (2008)

    African Journals Online (AJOL)

    The role of long-chain polyunsaturated fatty acids in the treatment of cancer cachexia and tumour growth in patients with malignant diseases: A review. EA Symington, GJ Gericke. http://dx.doi.org/10.4102/hsag.v13i2.279 ...

  10. Untitled

    African Journals Online (AJOL)

    retention and cachexia 8'9'10. Symptomatic prostate cancer is considered to be advanced disease“. However, not all prostate cancer patients in this series ' had orchidectomy. This accounts for the low proportion of patients with prostate cancer who had operations. In the period under study, urethral strictures requiring.

  11. Author Details

    African Journals Online (AJOL)

    Musa, A A. Vol 51, No 5 (2007) - Articles Omental cyst, an unusual cause of Cachexia Abstract. ISSN: 0189-0964. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL · News. OTHER ...

  12. Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI

    DEFF Research Database (Denmark)

    Tsai, Vicky Wang-Wei; Macia, Laurence; Feinle-Bisset, Christine

    2015-01-01

    The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy humans. Its levels rise substantially in cancer and other diseases and this may sometimes lead to development of an anorexia/cachexia syndrome. This is mediated by a direct action of MIC-1/GDF15 on feeding centres...

  13. Author Details

    African Journals Online (AJOL)

    Adebayo, S B. Vol 51, No 5 (2007) - Articles Omental cyst, an unusual cause of Cachexia Abstract · Vol 52, No 4 (2007) - Articles Ocular B-scan Ultrasound using non-dedicated Ultrasound system: Preliminary Report from Sagamu Abstract. ISSN: 0189-0964. AJOL African Journals Online. HOW TO USE AJOL.

  14. Ovine wet carcass syndrome of unknown aetiology

    African Journals Online (AJOL)

    plicating cachexia, inflammatory processes, lymphoedema, cardiac failure, glycogen storage or myxoedema in the pathogenesis of the syndrome. In conclusion, despite intensive investigation the aeti- ology of the wet carcase syndrome remains unknown. At present the possibility of a histamine reaction due to insect bites is ...

  15. Direct effects of TNF-α on local fuel metabolism and cytokine levels in the placebo controlled bilaterally infused human leg; increased insulin sensitivity, increased net protein breakdown and increased IL-6 release

    DEFF Research Database (Denmark)

    Bach, Ermina; Nielsen, Bent Roni Ranghøj; Vendelbo, Mikkel H

    2013-01-01

    . Insulin and protein signaling in muscle biopsies was not affected by TNF-α. TNF-α directly increased net muscle protein loss, which may contribute to cachexia and general protein loss during severe illness. The finding of increased insulin sensitivity, which could relate to IL-6, is of major clinical...

  16. First isolation and nucleotide comparison of the gag gene of the ...

    African Journals Online (AJOL)

    Caprine arthritis encephalitis virus (CAEV) has been reported in different countries worldwide, based on serological and molecular detection. In Argentina, the prevalence of CAEV infections is increasing, with goats showing symptoms associated mostly with cachexia and arthritis. Although in Argentina the virus has been ...

  17. Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B

    DEFF Research Database (Denmark)

    Olsen, Oddrun Elise; Wader, Karin Fahl; Hella, Hanne

    2015-01-01

    BACKGROUND: Activins are members of the TGF-β family of ligands that have multiple biological functions in embryonic stem cells as well as in differentiated tissue. Serum levels of activin A were found to be elevated in pathological conditions such as cachexia, osteoporosis and cancer. Signaling...

  18. May 2001

    African Journals Online (AJOL)

    2001-05-01

    May 1, 2001 ... weight loss (cachexia), constipation, nausea, vomiting, dizziness, anorexia and Troisier's sign(12). Late presentation of patients with gastric cancer has been noted in other places such as Ibadan hospital,. Nigeria(4), in Nyeri, Kenya( 1 ) and University of Medicine,. Texas, USA(2). The majority of patients ...

  19. Development and Evaluation of Adeno HTLV-III Hybrid Virus and Non- Cytopathic HTLV-III Mutant for Vaccine Use

    Science.gov (United States)

    1990-02-06

    Plasmid DNA was used to transform Escherichia coli (Z. gol") DH5 cells. Ampicillin-resistant transformants were screened on the basis of size and...important weight loss and cachexia. Autopsy showed that they both presented septicemia , one due to normal coliba- ciullus and the other to Klebsiela pn jia

  20. First report of citrus exocortis viroid and two citrus variants of the hop stunt viroid on lemon in Azerbaijan

    Science.gov (United States)

    Budwood received from a lemon tree growing at the Bioresources Institute Nakhichivan, Azerbaijan, produced symptoms corresponding with citrus viroids and cachexia on biological indicators ‘S-1’ citron and ‘Parson’s Special’ (PSM) mandarin, respectively. Sequential poly acrylamide gel electrophoresis...

  1. Aberrant brain microRNA target and miRISC gene expression in the anx/anx anorexia mouse model

    DEFF Research Database (Denmark)

    Mercader, Josep M; González, Juan R; Lozano, Juan José

    2012-01-01

    The anorexia mouse model, anx/anx, carries a spontaneous mutation not yet identified and homozygous mutants are characterized by anorexia-cachexia, hyperactivity, and ataxia. In order to test if the microRNA function was altered in these mice, hypothalamus and cortex transcriptomes were evaluated...

  2. Cryptosporidium varanii infection in leopard geckos ( Eublepharis ...

    African Journals Online (AJOL)

    ... pet leopard geckos (Eublepharis macularius) from a breeder colony in Buenos Aires, Argentina. Oocysts comparable to those of Cryptosporidium spp. were detected in three geckos with a history of diarrhea, anorexia and cachexia. Molecular identification methods confirmed the presence of Cryptosporidium varanii (syn.

  3. L-carnitine ameliorates the liver inflammatory response by regulating carnitine palmitoyltransferase I-dependent PPARγ signaling.

    Science.gov (United States)

    Jiang, Fang; Zhang, Zongqi; Zhang, Yi; Wu, Jianping; Yu, Li; Liu, Su

    2016-02-01

    The liver is crucial for systemic inflammation in cancer cachexia. Previous studies have shown that L-carnitine, as the key regulator of lipid metabolism, exerts an anti-inflammatory effect in several diseases, and ameliorates the symptoms of cachexia by regulating the expression and activity of carnitine palmitoyltransferase (CPT) in the liver. However, the effect of L-carnitine on the liver inflammatory response in cancer cachexia remains to be elucidated. The aim of the present study was to examine the role of the CPT I-dependent peroxisome proliferator-activated receptor (PPAR)γ signaling pathway in the ameliorative effect of L-carnitine on the liver inflammatory response. This was investigated in a colon-26 tumor-bearing mouse model with cancer cachexia. Liver sections were immunohistochemically analyzed, and mRNA and protein levels of representative molecules of the CPT-associated PPARγ signaling pathway were assessed using PCR and western blot analysis, respectively. The results showed that oral administration of L-carnitine in these mice improved hepatocyte necrosis, liver cell cord derangement and hydropic or fatty degeneration of the liver cells in the liver tissues, decreased serum levels of malondialdehyde, increased serum levels of superoxide dismutase and glutathione peroxidase, and elevated the expression levels of PPARα and PPARγ at the mRNA and protein levels. These changes induced by L-carnitine were reversed by treatment with etomoxir, an inhibitor of CPT I. The inhibitory effect of L-carnitine on the increased expression level of nuclear factor (NF)-κB p65 in the peripheral blood mononuclear cells was markedly weakened by GW9662, a selective inhibitor of PPAR-γ. GW9662 also eliminated the inhibitory effect of L-carnitine on the expression of cyclooxygenase-2 (Cox-2) in the liver, and on the serum expression levels of pro-inflammatory prostaglandin E2, C-reactive protein, tumor necrosis factor-α and interleukin-6 in the cancer cachexia

  4. Post-diagnosis weight loss as a prognostic factor in non-small cell lung cancer.

    Science.gov (United States)

    Mytelka, Daniel S; Li, Li; Benoit, Karin

    2017-12-04

    Cachexia and its most visible manifestation, weight loss, represent important poor prognostic factors for patients with non-small cell lung cancer. This work examines how severity of weight loss as an indicator of cachexia affects outcomes. In a retrospective observational study of electronic medical records, patients with non-small cell lung cancer were monitored for weight loss from an initial assessment (within 2 months of index diagnosis) to a landmark at 5 months (at least 3 months after initial assessment). Patients who survived to the landmark were then followed to determine the association of baseline body mass index (BMI) and weight loss during the assessment period with outcomes. Patients were clustered to determine how BMI and weight loss related to survival as approximated by time of last appearance in the database, a strong proxy for time of death. Twelve thousand one hundred and one patients were divided into 5 cachexia risk groups based on a combination of weight loss and initial BMI. More severe groups demonstrated progressively worse outcomes, with the most severe group surviving for a median of 263 days (95% CI 254-274) from index and having a 1-year survival rate of 31%. The least severe group survived for a median of 825 days from index (95% CI 768-908) and had a 1-year survival rate of 78%. Cachexia risk group was a stronger predictor of survival than any baseline variable, including disease stage, performance status, or age. In this study, we showed that increasing weight loss and, to a lesser extent, decreasing BMI, led to substantially worse outcomes for non-small cell lung cancer patients independent of other variables. We suggest risk score groups that provide an improved approach for identifying poor prognosis patients with the greatest need. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  5. Nutritional problems among patients affected by cancer during chemotherapy

    Directory of Open Access Journals (Sweden)

    Marzena Kamińska

    2016-01-01

    Full Text Available Chemotherapy is one of the primary methods of treating cancer. Symptoms occurring during this form of therapy affect patients’ general health status, cause malnutrition, and deteriorate the quality of life of oncology patients, which results in cachexia. Malnutrition during treatment and the resulting bad general health status of patients may lead to disqualification from chemotherapy treatment. Cachexia is a complex and multi-factorial process, characterised by the nearly unknown mechanism of its development. What is extremely crucial is the evaluation of the state of malnutrition among patients qualified for cytostatic therapy and regular control of this state during therapy and immediately after its termination. Clinical practice indicates the importance of applying pharmacotherapy, nutritional treatment, and targeted education for the patient and their closest family regarding diet and correct behaviour, which significantly reduces anxiety and stress.

  6. Extreme Achalasia Presenting as Anorexia Nervosa

    Directory of Open Access Journals (Sweden)

    P. J. Goldsmith

    2012-01-01

    Full Text Available Background. Achalasia may lead to cachexia if not diagnosed in an early stage. Surgery in cachectic patients is hazardous and complications may result in a protracted recovery or even death. Different treatment options have been described. In this paper, we report a stepwise surgical laparoscopic approach which appears to be safe and effective. Methods. Over a one-year period, a patient with a body mass index (BMI below 17 being treated for anorexia nervosa was referred with dysphagia. Because of the extreme cachexia, a laparoscopic feeding jejunostomy (LFJ was fashioned to enable long-term home enteral feeding. The patient underwent a laparoscopic Heller myotomy (LHM when the BMI was normal. Results. The patient recovered well following this stepwise approach. Conclusion. Patients with advanced achalasia usually present with extreme weight loss. In this small group of patients, a period of home enteral nutrition (HEN via a laparoscopically placed feeding jejunostomy allows weight gain prior to safe definitive surgery.

  7. Signaling pathways controlling skeletal muscle mass.

    Science.gov (United States)

    Egerman, Marc A; Glass, David J

    2014-01-01

    The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed "atrophy", is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle.

  8. How wasting is saving: weight loss at altitude might result from an evolutionary adaptation.

    Science.gov (United States)

    Murray, Andrew J; Montgomery, Hugh E

    2014-08-01

    At extreme altitude (>5,000 - 5,500 m), sustained hypoxia threatens human function and survival, and is associated with marked involuntary weight loss (cachexia). This seems to be a coordinated response: appetite and protein synthesis are suppressed, and muscle catabolism promoted. We hypothesise that, rather than simply being pathophysiological dysregulation, this cachexia is protective. Ketone bodies, synthesised during relative starvation, protect tissues such as the brain from reduced oxygen availability by mechanisms including the reduced generation of reactive oxygen species, improved mitochondrial efficiency and activation of the ATP-sensitive potassium (KATP ) channel. Amino acids released from skeletal muscle also protect cells from hypoxia, and may interact synergistically with ketones to offer added protection. We thus propose that weight loss in hypoxia is an adaptive response: the amino acids and ketone bodies made available act not only as metabolic substrates, but as metabolic modulators, protecting cells from the hypoxic challenge. © 2014 The Authors. Bioessays published by WILEY Periodicals, Inc.

  9. MUSCLE WASTING AND CARDIAC MUSCLE DAMAGE IN CACHECTIC PATIENTS

    Directory of Open Access Journals (Sweden)

    Claudia Sangiorgi

    2013-04-01

    Full Text Available Muscle wasting is a degeneration of the muscle tissue that can derive from several pathological situations, but most of the times is caused by a condition of cachexia in patients with cancer or other diseases. This degeneration results from a decrease in protein synthesis and an increase in protein degradation. This is caused mainly by the overexpression of ubiquitin-proteosome-system (UPS elements, under the control of factors released in cachexia that lead cells toward a catabolic rather than an anabolic pathway. Both skeletal and cardiac muscles can be affected by muscle wasting and until now an effective treatment is unknown. Only experimental trials of exercise training bring to a recovery of mass loss, but many researchers think that a potential future treatment may be represented by stem cells.

  10. Lentinan: hematopoietic, immunological, and efficacy studies in a syngeneic model of acute myeloid leukemia.

    Science.gov (United States)

    McCormack, Emmet; Skavland, Jørn; Mujic, Maja; Bruserud, Øystein; Gjertsen, Bjørn Tore

    2010-01-01

    Lentinan, a beta-glucan nutritional supplement isolated from the shitake mushroom (Lentula edodes), is a biological response modifier with immunostimulatory properties. Concomitantly, the role of beta-glucans as chemoimmunotherapeutic in a number of solid cancers has been widely documented. We investigated the effects of nutritional grade lentinan upon BN rats and in a preclinical syngeneic model of acute myeloid leukemia. BN rats supplemented daily with lentinan exhibited weight gains, increased white blood cells, monocytes, and circulating cytotoxic T-cells; and had a reduction in anti-inflammatory cytokines IL-4, IL-10, and additionally IL-6. Lentinan treatment of BN rats with BNML leukemia resulted in improved cage-side health and reduced cachexia in the terminal stage of this aggressive disease. Combination of lentinan with standards of care in acute myeloid leukemia, idarubicin, and cytarabine increased average survival compared with monotherapy and reduced cachexia. These results indicate that nutritional supplementation of cancer patients with lentinan should be further investigated.

  11. Of faeces and sweat. How much a mouse is willing to run: having a hard time measuring spontaneous physical activity in different mouse sub-strains

    Directory of Open Access Journals (Sweden)

    Dario Coletti

    2017-03-01

    Full Text Available Physical activity has multiple beneficial effects in the physiology and pathology of the organism. In particular, we and other groups have shown that running counteracts cancer cachexia in both humans and rodents. The latter are prone to exercise in wheel-equipped cages even at advanced stages of cachexia. However, when we wanted to replicate the experimental model routinely used at the University of Rome in a different laboratory (i.e. at Paris 6 University, we had to struggle with puzzling results due to unpredicted mouse behavior. Here we report the experience and offer the explanation underlying these apparently irreproducible results. The original data are currently used for teaching purposes in undergraduate student classes of biological sciences.

  12. Early Parenteral Nutrition in Patients with Biliopancreatic Mass Lesions, a Prospective, Randomized Intervention Trial

    OpenAIRE

    Kr?ger, Janine; Meffert, Peter J.; Vogt, Lena J.; G?rtner, Simone; Steveling, Antje; Kraft, Matthias; Mayerle, Julia; Lerch, Markus M.; Aghdassi, Ali A.

    2016-01-01

    Purpose Patients with biliopancreatic tumors frequently suffer from weight loss and cachexia. The in-hospital work-up to differentiate between benign and malignant biliopancreatic lesions requires repeated pre-interventional fasting periods that can aggravate this problem. We conducted a randomized intervention study to test whether routine in-hospital peripheral intravenous nutrition on fasting days (1000 ml/24 h, 700 kcal) has a beneficial effect on body weight and body composition. Materia...

  13. Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment

    OpenAIRE

    Chung, Hae-Yun; Park, Yoo Kyoung

    2017-01-01

    Ketogenic diet has been used for more than 80 years as a successful dietary regimen for epilepsy. Recently, dietary modulation by carbohydrate depletion via ketogenic diet has been suggested as an important therapeutic strategy to selectively kill cancer cells and as adjuvant therapy for cancer treatment. However, some researchers insist ketogenic diet to be highly undesirable as ketogenic diet may trigger and/or exacerbate cachexia development and usually result in significant weight loss. T...

  14. Invalidation du gène de la myostatine dans un modèle murin de cachexie associée au cancer : implication dans la régulation de la masse musculaire

    OpenAIRE

    Gallot, Yann

    2013-01-01

    Cachexia is a complex clinical and metabolic syndrome, whose definition is imprecise, characterized by an uncontrolled loss of adipose tissue and skeletal muscle mass, frequently observed in cancer patients, and leading to death in 25% of cancer patients. Myostatin (Mstn) is a negative regulator of skeletal muscle mass and a critical determinant of skeletal muscle homeostasis. Although the regulation of the molecular mechanisms involved in the control of skeletal muscle mass plays a central r...

  15. Recommendations from SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA on nutrition in the HIV-infected patient Recomendaciones de SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA sobre nutrición en el paciente con infección por VIH

    OpenAIRE

    R. Polo; C. Gómez-Candela; C Miralles; Locutura, J.; J Álvarez; Barreiro, F.; Bellido, D; E. Câncer; D. Cánoves; Domingo, P; Estrada, V; C. R. Fumaz; M. J. Galindo; T. García-Benayas; Iglesias, C.

    2007-01-01

    Objective: to make recommendations on the approach to nutritional problems (malnutrition, cachexia, micronutrient deficiency, obesity, lipodystrophy) affecting HIV-infected patients. Methods: these recommendations have been agreed upon by a group of expertes in the nutrition and care of HIV-infected patients, on behalf of the different groups involved in drafting them. Therefore, the latest advances in pathophysiology, epidemiology, and clinical care presented in studies published in medical ...

  16. A clinical approach to the nutritional care process in protein-energy wasting hemodialysis patients.

    Science.gov (United States)

    Ruperto, Mar; Sánchez-Muniz, Francisco J; Barril, Guillermina

    2014-04-01

    Malnutrition/wasting/cachexia are complex-disease conditions that frequently remain undiagnosed and/or untreated in up to 75% of prevalent hemodialysis (HD) patients. The nutrition care process (NCP) based on assessment, diagnosis, intervention and monitoring of nutritional status is a systematic method that nutrition professionals use to make decisions in clinical practice. This review examines from a clinical-nutritional practice point of view: a) nutritional status as a mortality causative factor; b) phenotypic characteristics of malnutrition/wasting/cachexia, and c) current trends of NCP with special emphasis on nutritional support and novel nutrient and pharmacologic adjunctive therapies in HD patients. A literature review was conducted using the Pubmed, Science Direct, Scielo, Scopus, and Medline electronic scientific basis. Studies which assessing nutritional status and nutritional support published from 1990 to 2013 in HD patients were included and discussed. From all the epidemiological data analyzed, NCP was the suggested method for identifying malnutrition/ wasting or cachexia in clinical practice. Nutrition support as an unimodal therapy was not completely able to reverse wasting in HD patients. Novel experimental therapeutic strategies including the use of appetite stimulants, ghrelin agonist, MC4-R antagonists, anabolic steroids, anti-inflammatory drugs, cholecalciferol, and other components are still under clinical evaluation. Nutritional status is a strong predictor of morbidity and mortality in HD patients. The terms called malnutrition, wasting and cachexia have different nutritional therapeutics implications. The NCP is a necessary tool for assessing and monitoring nutritional status in the current clinical practice. Novel pharmacological therapies or specific nutrient supplementation interventions studies are required. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  17. Pharmacology of anabolic steroids

    OpenAIRE

    Kicman, A T

    2008-01-01

    Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and ...

  18. The Emerging Role of Skeletal Muscle Metabolism as a Biological Target and Cellular Regulator of Cancer-Induced Muscle Wasting

    OpenAIRE

    Carson, James A.; Hardee, Justin P.; VanderVeen, Brandon N.

    2015-01-01

    While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle���s metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the...

  19. Regulation of Energy Balance by Inflammation: Common Theme in Physiology and Pathology

    OpenAIRE

    Wang, Hui; Ye, Jianping

    2015-01-01

    Inflammation regulates energy metabolism in both physiological and pathological conditions. Pro-inflammatory cytokines involves in energy regulation in several conditions, such as obesity, aging (calorie restriction), sports (exercise), and cancer (cachexia). Here, we introduce a view of integrative physiology to understand pro-inflammatory cytokines in the control of energy expenditure. In obesity, chronic inflammation is derived from energy surplus that induces adipose tissue expansion and ...

  20. In Reply

    OpenAIRE

    Champ, Colin E; Simone, Nicole L.

    2013-01-01

    In response to Dr. Klement's comments, Drs. Simone and Champ agree that a ketogenic diet (KD) may be added as a dietary intervention in cancer treatment. They suggest that patients with certain cancers that put them at risk for cachexia may respond best to a KD, whereas patients with cancers that do worse with weight gain might benefit more from calorie restriction or intermittent fasting.

  1. Ghrelin administration suppresses inflammation-associated colorectal carcinogenesis in mice

    OpenAIRE

    Kawaguchi, Makiko; Kanemaru, Ai; FUKUSHIMA, Tsuyoshi; Yamamoto, Koji; Tanaka, Hiroyuki; Haruyama, Yukihiro; Itoh, Hiroshi; MATSUMOTO, Nobuhiro; Kangawa, Kenji; Nakazato, Masamitsu; Kataoka, Hiroaki

    2015-01-01

    Ghrelin is a 28-amino-acid peptide that stimulates the release of pituitary growth hormone. Because of its orexigenic effects, ghrelin is being developed as a therapeutic option for postoperative support and treatment of anorexia-cachexia syndrome of cancer patients. However, ghrelin has a multiplicity of physiological functions, and it also affects cell proliferation. Therefore, the effects of ghrelin administration on carcinogenesis and cancer progression in patients susceptible to cancer s...

  2. Guidelines for specialized nutritional and metabolic support in the critically-ill patient: Update. Consensus SEMICYUC-SENPE: Cardiac patient Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico: Actualización. Consenso SEMICYUC-SENPE: Paciente cardíaco

    OpenAIRE

    F. J. Jiménez Jiménez; M. Cervera Montes; A. L. Blesa Malpica

    2011-01-01

    Patients with cardiac disease can develop two types of malnutrition: cardiac cachexia, which appears in chronic congestive heart failure, and malnutrition due to the complications of cardiac surgery or any other type of surgery in patients with heart disease. Early enteral nutrition should be attempted if the oral route cannot be used. When cardiac function is severely compromised, enteral nutrition is feasible, but supplementation with parenteral nutrition is sometimes required. Sustained hy...

  3. Conjugated Linoleic Acid: good or bad nutrient

    Directory of Open Access Journals (Sweden)

    Gonçalves Daniela C

    2010-10-01

    Full Text Available Abstract Conjugated linoleic acid (CLA is a class of 28 positional and geometric isomers of linoleic acid octadecadienoic.Currently, it has been described many benefits related to the supplementation of CLA in animals and humans, as in the treatment of cancer, oxidative stress, in atherosclerosis, in bone formation and composition in obesity, in diabetes and the immune system. However, our results show that, CLA appears to be not a good supplement in patients with cachexia.

  4. Ghrelin, a novel peptide hormone in the regulation of energy balance and cardiovascular function.

    Science.gov (United States)

    Ledderose, Carola; Kreth, Simone; Beiras-Fernandez, Andres

    2011-01-01

    Ghrelin, a peptide hormone predominantly produced by the stomach, is a potent stimulator of growth hormone release, food intake and weight gain. Besides its functions in regulating energy homeostasis, ghrelin has pronounced cardioprotective effects and was shown to improve cardiac performance in chronic heart failure (CHF). The multifunctional nature of ghrelin makes it an interesting pharmacological target for various diseases. Inhibition of ghrelin could be a promising approach in obesity-related disorders, while an enhancement of the ghrelin response is considered beneficial in several pathologic conditions marked by malnutrition, wasting and cachexia, including CHF, cancer, chronic pulmonary disease or chronic infections. In particular, patients suffering from CHF could possibly benefit from ghrelin based compounds that do not only help to reverse cardiac cachexia - by inducing a positive energy balance - but also enhance the direct cardioprotective effects of ghrelin. This review highlights the role of ghrelin in the regulation of energy balance and cardiovascular function and summarizes the most recent patents, developments and strategies in ghrelin-based pharmacotherapy for the treatment of pathologic conditions associated with obesity, cachexia or cardiovascular dysfunction.

  5. Osteolytic Breast Cancer Causes Skeletal Muscle Weakness in an Immunocompetent Syngeneic Mouse Model

    Directory of Open Access Journals (Sweden)

    Jenna N. Regan

    2017-12-01

    Full Text Available Muscle weakness and cachexia are significant paraneoplastic syndromes of many advanced cancers. Osteolytic bone metastases are common in advanced breast cancer and are a major contributor to decreased survival, performance, and quality of life for patients. Pathologic fracture caused by osteolytic cancer in bone (OCIB leads to a significant (32% increased risk of death compared to patients without fracture. Since muscle weakness is linked to risk of falls which are a major cause of fracture, we have investigated skeletal muscle response to OCIB. Here, we show that a syngeneic mouse model of OCIB (4T1 mammary tumor cells leads to cachexia and skeletal muscle weakness associated with oxidation of the ryanodine receptor and calcium (Ca2+ release channel (RyR1. Muscle atrophy follows known pathways via both myostatin signaling and expression of muscle-specific ubiquitin ligases, atrogin-1 and MuRF1. We have identified a mechanism for skeletal muscle weakness due to increased oxidative stress on RyR1 via NAPDH oxidases [NADPH oxidase 2 (Nox2 and NADPH oxidase 4 (Nox4]. In addition, SMAD3 phosphorylation is higher in muscle from tumor-bearing mice, a critical step in the intracellular signaling pathway that transmits TGFβ signaling to the nucleus. This is the first time that skeletal muscle weakness has been described in a syngeneic model of OCIB and represents a unique model system in which to study cachexia and changes in skeletal muscle.

  6. Nutrient interaction for optimal protein anabolism in resistance exercise.

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    Breen, Leigh; Phillips, Stuart M

    2012-05-01

    The rapid muscle loss that accompanies varying diseased states (cachexia) is due to an imbalance between muscle protein synthesis (MPS) and muscle protein breakdown In the current review, we will discuss and summarize recent evidence in order to provide practical recommendations on exercise and nutrient interventions for cachectic populations. Resistance exercise is a potent stimulus for MPS, but cachexia patients may not be best placed to lift the heavy loads that, it was previously assumed, were a prerequisite for muscle hypertrophy. However, recent evidence from our lab shows that lower loads can effectively stimulate MPS and lead to hypertrophy. Protein ingestion potentiates resistance exercise-induced rates of MPS. The source and dose of the ingested protein are important to consider when attempting to maximize postresistance exercise MPS. Specifically, rapidly digested, leucine-rich protein sources may stimulate greater postexercise rates of MPS than other protein sources, as leucine acts as a key anabolic signal for mRNA translation. Furthermore, individuals undergoing relatively slow muscle atrophy (i.e., in sarcopenic elderly) respond positively to larger doses (40  g) of amino acids following exercise, whereas the response appears to plateau after moderate doses (20  g) in healthy, young adults. Emerging evidence shows that manipulating traditional exercise loading and nutrient strategies may ameliorate cachexia.

  7. The Emerging Role of Skeletal Muscle Metabolism as a Biological Target and Cellular Regulator of Cancer-Induced Muscle Wasting

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    Carson, James A.; Hardee, Justin P.; VanderVeen, Brandon N.

    2015-01-01

    While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle’s metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the historical assessment of mitochondria content and function during cancer-induced muscle loss was closely aligned with energy flux and wasting susceptibility, this understanding has expanded to link mitochondria dysfunction to cellular processes regulating myofiber wasting. The primary objective of this article is to highlight muscle mitochondria and oxidative metabolism as a biological target of cancer cachexia and also as a cellular regulator of cancer-induced muscle wasting. Initially, we examine the role of muscle metabolic phenotype and mitochondria content in cancer-induced wasting susceptibility. We then assess the evidence for cancer-induced regulation of skeletal muscle mitochondrial biogenesis, dynamics, mitophagy, and oxidative stress. In addition, we discuss environments associated with cancer cachexia that can impact the regulation of skeletal muscle oxidative metabolism. The article also examines the role of cytokine-mediated regulation of mitochondria function regulation, followed by the potential role of cancer-induced hypogonadism. Lastly, a role for decreased muscle use in cancer-induced mitochondrial dysfunction is reviewed. PMID:26593326

  8. Nutrition and cancer. Recent developments.

    Science.gov (United States)

    Ogilvie, G K; Vail, D M

    1990-07-01

    Cancer cachexia is a complex syndrome that results in involuntary weight loss, even in the face of adequate nutritional intake. The profound metabolic abnormalities associated with cancer cachexia affect a large percentage of animals with cancer even before any clinical signs are seen. This paraneoplastic syndrome results in alterations in carbohydrate, lipid, and protein metabolism that, if left untreated, decrease the animal's quality of life and lead to a poor response to cancer therapy. An understanding of the metabolic abnormalities associated with cancer cachexia is of paramount importance to the practicing veterinarian to determine an accurate prognosis and to choose the optimal type of intravenous fluids and nutritional therapy for each patient. Although research identifying the optimal diet for cancer-bearing dogs and cats is still underway, some general principles apply. The first is that the patient should receive nutritional elements orally whenever possible. When oral feeding is not possible, nasogastric, gastrostomy, and jejunostomy tube feeding are viable options. When feeding by the gastrointestinal tract is not possible, parenteral feeding is a practical alternative.

  9. Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer.

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    Peter Arner

    Full Text Available Cancer cachexia (CC is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia.Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32 or without (n = 27 cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer.Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1 was confirmed by sandwich immunoassay to be lower in CC (p = 0.008. In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results.In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.

  10. The "parallel pathway": a novel nutritional and metabolic approach to cancer patients.

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    Muscaritoli, Maurizio; Molfino, Alessio; Gioia, Gianfranco; Laviano, Alessandro; Rossi Fanelli, Filippo

    2011-04-01

    Cancer-associated malnutrition results from a deadly combination of anorexia, which leads to reduced food intake, and derangements of host metabolism inducing body weight loss, and hindering its reversal with nutrient supplementation. Cancer patients often experience both anorexia and weight loss, contributing to the onset of the clinical feature named as anorexia-cachexia syndrome. This condition has a negative impact upon patients' nutritional status. The pathogenesis of the anorexia-cachexia syndrome is multifactorial, and is related to: tumour-derived factors, host-derived factors inducing metabolic derangements, and side effects of anticancer therapies. In addition, the lack of awareness of cancer patients' nutritional issues and status by many oncologists, frequently results in progressive weight loss going undiagnosed until it becomes severe. The critical involvement of host inflammatory response in the development of weight loss, and, in particular, lean body mass depletion, limits the response to the provision of standard nutrition support. A novel nutritional and metabolic approach, named "parallel pathway", has been devised that may help maintain or improve nutritional status, and prevent or delay the onset of cancer cachexia. Such an approach may improve tolerance to aggressive anticancer therapies, and ameliorate the functional capacity and quality of life even in advanced disease stages. The "parallel pathway" implies a multiprofessional and multimodal approach aimed at ensuring early, appropriate and continuous nutritional and metabolic support to cancer patients in any phase of their cancer journey.

  11. Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect.

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    Beluzi, Mércia; Peres, Sidney B; Henriques, Felipe S; Sertié, Rogério A L; Franco, Felipe O; Santos, Kaltinaitis B; Knobl, Pâmela; Andreotti, Sandra; Shida, Cláudio S; Neves, Rodrigo X; Farmer, Stephen R; Seelaender, Marília; Lima, Fábio B; Batista, Miguel L

    2015-01-01

    Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ) was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107) of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control) and TP5 (tumor + PGZ/5 mg). Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT) depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group). The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01) when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01) on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05) and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT) mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-γ, adiponectin, LPL and C/EBP-α from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT) was entirely re-established due to

  12. Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect.

    Directory of Open Access Journals (Sweden)

    Mércia Beluzi

    Full Text Available Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107 of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control and TP5 (tumor + PGZ/5 mg. Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group. The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01 when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01 on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05 and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-γ, adiponectin, LPL and C/EBP-α from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT was entirely re

  13. Ghrelin and its analogues, BIM-28131 and BIM-28125, improve body weight and regulate the expression of MuRF-1 and MAFbx in a rat heart failure model.

    Directory of Open Access Journals (Sweden)

    Sandra Palus

    Full Text Available Cardiac cachexia is a serious complication of chronic heart failure with a prevalence of 10-16% and poor prognosis. There are no current therapy options for cardiac cachexia. Ghrelin is the natural ligand for the GHS-1a-receptor and a potential target for conditions associated with cachexia. Ghrelin has been shown to increase weight in several species. The GHS-1a-receptor is not only found in the brain, but also in other tissues, including the myocardium. Human clinical trials with native ghrelin in cardiac cachexia demonstrated increases in appetite, weight and cardiac output.Human ghrelin or one of two analogues BIM-28125 and BIM-28131 (also known as RM-131 were tested at 50 nmole/kg/d and 500 nmole/kg/d versus placebo in a rat model of heart failure (myocardial infarction. Animals (SD-rats, approx. 225 g at surgery received diuretics from day 14 and compounds from day 28 for 4 weeks using osmotic pumps. Weight was monitored and body composition analysed (NMR-scanning. Cardiac function was assessed by echocardiography and hemodynamics.Animals with MI gained less weight compared to sham rats until start of the therapy (311 g vs 324 g, p = 0.0129. Animals treated with BIM-28131 at 50 nmole/kg/d or all compounds at 500 nmole/kg/d displayed stronger weight gain compared to placebo and sham (all p<0.001. Before treatment, body composition was similar in all groups (average: 36 g fat, 248 g lean. Placebo-treated rats gained no fat, but only lean mass. The active compounds induced both fat and lean mass gain, but to a different extent. The fat-to-muscle-ratio of tissue gain was 0.9±0.07 for BIM-28131 at 50 nmole/kg/d, whereas at 500 nmole/kg/d it was 0.76±0.07 for BIM-28131, 0.68±0.12 for BIM-28125, and 0.48±0.05 for ghrelin. MuRF-1 and MAFbx were differentially regulated by treatment.Ghrelin is a very promising treatment option for cardiac cachexia, with the analogue BIM-28131 (RM-131 being the most effective compound.

  14. Insulin, not glutamine dipeptide, reduces lipases expression and prevents fat wasting and weight loss in Walker 256 tumor-bearing rats.

    Science.gov (United States)

    de Morais, Hely; de Fatima Silva, Flaviane; da Silva, Francemilson Goulart; Silva, Milene Ortiz; Graciano, Maria Fernanda Rodrigues; Martins, Maria Isabel Lovo; Carpinelli, Ângelo Rafael; Mazucco, Tânia Longo; Bazotte, Roberto Barbosa; de Souza, Helenir Medri

    2017-07-05

    Cachexia is the main cause of mortality in advanced cancer patients. We investigated the effects of insulin (INS) and glutamine dipeptide (GDP), isolated or associated, on cachexia and metabolic changes induced by Walker 256 tumor in rats. INS (NPH, 40 UI/kg, sc) or GDP (1.5g/kg, oral gavage) was once-daily administered during 11 days after tumor cell inoculation. GDP, INS or INS+GDP treatments did not influence the tumor growth. However, INS and INS+GDP prevented retroperitoneal fat wasting and body weight loss of tumor-bearing rats. In consistency, INS and INS+GDP prevented the increased expression of triacylglycerol lipase (ATGL) and hormone sensitive lipase (HSL), without changing the expression of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in the retroperitoneal adipose tissue of tumor-bearing rats. INS and INS+GDP also prevented anorexia and hyperlactatemia of tumor-bearing rats. However, INS and INS+GDP accentuated the loss of muscle mass (gastrocnemius, soleus and long digital extensor) without affecting the myostatin expression in the gastrocnemius muscle and blood corticosterone. GDP treatment did not promote beneficial effects. It can be concluded that treatment with INS (INS or INS+GDP), not with GDP, prevented fat wasting and weight loss in tumor-bearing rats without reducing tumor growth. These effects might be attributed to the reduction of lipases expression (ATGL and LHS) and increased food intake. The results show the physiological function of INS in the suppression of lipolysis induced by cachexia mediators in tumor-bearing rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Cockayne syndrome in adults: review with clinical and pathologic study of a new case.

    Science.gov (United States)

    Rapin, Isabelle; Weidenheim, Karen; Lindenbaum, Yelena; Rosenbaum, Pearl; Merchant, Saumil N; Krishna, Sindu; Dickson, Dennis W

    2006-11-01

    Cockayne syndrome and xeroderma pigmentosum-Cockayne syndrome complex are rare autosomal recessive disorders with poorly understood biology. They are characterized by profound postnatal brain and somatic growth failure and by degeneration of multiple tissues resulting in cachexia, dementia, and premature aging. They result in premature death, usually in childhood, exceptionally in adults. This study compares the clinical course and pathology of a man with Cockayne syndrome group A who died at age 31(1/2) years with 15 adequately documented other adults with Cockayne syndrome and 5 with xeroderma pigmentosum-Cockayne syndrome complex. Slowing of head and somatic growth was apparent before age 2 years, mental retardation and slowly progressive spasticity at 4 years, ataxia and hearing loss at 9 years, visual impairment at 14 years, typical Cockayne facies at 17 years, and cachexia and dementia in his twenties, with a retained outgoing personality. He experienced several transient right and left hemipareses and two episodes of status epilepticus following falls. Neuropathology disclosed profound microencephaly, bilateral old subdural hematomas, white-matter atrophy, tigroid leukodystrophy with string vessels, oligodendrocyte proliferation, bizarre reactive astrocytes, multifocal dystrophic calcification that was most marked in the basal ganglia, advanced atherosclerosis, mixed demyelinating and axonal neuropathy, and neurogenic muscular atrophy. Cellular degeneration of the organ of Corti, spiral and vestibular ganglia, and all chambers of the eye was severe. Rarely, and for unexplained reasons, in some patients with Cockayne syndrome the course is slower than usual, resulting in survival into adulthood. The profound dwarfing, failure of brain growth, cachexia, selectivity of tissue degeneration, and poor correlation between genotypes and phenotypes are not understood. Deficient repair of DNA can increase vulnerability to oxidative stress and play a role in the

  16. Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

    Science.gov (United States)

    Rapin, Isabelle; Weidenheim, Karen; Lindenbaum, Yelena; Rosenbaum, Pearl; Merchant, Saumil N.; Krishna, Sindu; Dickson, Dennis W.

    2009-01-01

    Cockayne syndrome and xeroderma pigmentosum–Cockayne syndrome complex are rare autosomal recessive disorders with poorly understood biology. They are characterized by profound postnatal brain and somatic growth failure and by degeneration of multiple tissues resulting in cachexia, dementia, and premature aging. They result in premature death, usually in childhood, exceptionally in adults. This study compares the clinical course and pathology of a man with Cockayne syndrome group A who died at age 31½ years with 15 adequately documented other adults with Cockayne syndrome and 5 with xeroderma pigmentosum–Cockayne syndrome complex. Slowing of head and somatic growth was apparent before age 2 years, mental retardation and slowly progressive spasticity at 4 years, ataxia and hearing loss at 9 years, visual impairment at 14 years, typical Cockayne facies at 17 years, and cachexia and dementia in his twenties, with a retained outgoing personality. He experienced several transient right and left hemipareses and two episodes of status epilepticus following falls. Neuropathology disclosed profound microencephaly, bilateral old subdural hematomas, white-matter atrophy, tigroid leukodystrophy with string vessels, oligodendrocyte proliferation, bizarre reactive astrocytes, multifocal dystrophic calcification that was most marked in the basal ganglia, advanced atherosclerosis, mixed demyelinating and axonal neuropathy, and neurogenic muscular atrophy. Cellular degeneration of the organ of Corti, spiral and vestibular ganglia, and all chambers of the eye was severe. Rarely, and for unexplained reasons, in some patients with Cockayne syndrome the course is slower than usual, resulting in survival into adulthood. The profound dwarfing, failure of brain growth, cachexia, selectivity of tissue degeneration, and poor correlation between genotypes and phenotypes are not understood. Deficient repair of DNA can increase vulnerability to oxidative stress and play a role in the

  17. Association of sarcopenia and observed physical performance with attainment of multidisciplinary team planned treatment in non-small cell lung cancer: an observational study protocol.

    Science.gov (United States)

    Collins, Jemima T; Noble, Simon; Chester, John; Davies, Helen E; Evans, William D; Lester, Jason; Parry, Diane; Pettit, Rebecca J; Byrne, Anthony

    2015-07-24

    Non-small cell lung cancer (NSCLC) frequently presents in advanced stages. A significant proportion of those with reportedly good ECOG performance status (PS) fail to receive planned multidisciplinary team (MDT) treatment, often for functional reasons, but an objective decline in physical performance is not well described. Sarcopenia, or loss of muscle mass, is an integral part of cancer cachexia. However, changes in both muscle mass and physical performance may predate clinically overt cachexia, and may be present even with normal body mass index. Physical fitness for treatment is currently subjectively assessed by means of the PS score, which may be inadequate in predicting tolerance to treatment. This study aims to evaluate whether measuring physical performance and muscle mass at baseline in NSCLC patients, in addition to PS score, is able to predict commencement and successful completion of MDT-planned treatment. This is a prospective, single-centre exploratory study of NSCLC patients attending a Rapid Access Lung Cancer clinic. Baseline data collected are (methods in brackets): physical performance (Short Physical Performance Battery), muscle mass (bioelectrical impedance ± dual energy x-ray absorptiometry), patient and physician-assessed PS (ECOG and Karnofsky), nutritional status and presence of cachexia. Longitudinal data consists of receipt and completion of MDT treatment plan. The primary outcome measure is commencement of MDT-planned treatment, and important secondary outcomes include successful completion of treatment, length of stay in surgical patients, and risk of chemotherapy- and radiotherapy-related side effects. A more comprehensive assessment of phenotype, particularly with regards to physical performance and muscle mass, will provide additional discriminatory information of patients' fitness for treatment. If positive, this study has the potential to identify targets for early intervention in those who are at risk of deterioration. This will

  18. Regulation of energy balance by inflammation: common theme in physiology and pathology.

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    Wang, Hui; Ye, Jianping

    2015-03-01

    Inflammation regulates energy metabolism in both physiological and pathological conditions. Pro-inflammatory cytokines involves in energy regulation in several conditions, such as obesity, aging (calorie restriction), sports (exercise), and cancer (cachexia). Here, we introduce a view of integrative physiology to understand pro-inflammatory cytokines in the control of energy expenditure. In obesity, chronic inflammation is derived from energy surplus that induces adipose tissue expansion and adipose tissue hypoxia. In addition to the detrimental effect on insulin sensitivity, pro-inflammatory cytokines also stimulate energy expenditure and facilitate adipose tissue remodeling. In caloric restriction (CR), inflammatory status is decreased by low energy intake that results in less energy supply to immune cells to favor energy saving under caloric restriction. During physical exercise, inflammatory status is elevated due to muscle production of pro-inflammatory cytokines, which promote fatty acid mobilization from adipose tissue to meet the muscle energy demand. In cancer cachexia, chronic inflammation is elevated by the immune response in the fight against cancer. The energy expenditure from chronic inflammation contributes to weight loss. Immune tolerant cancer cells gains more nutrients during the inflammation. In these conditions, inflammation coordinates energy distribution and energy demand between tissues. If the body lacks response to the pro-inflammatory cytokines (Inflammation Resistance), the energy metabolism will be impaired leading to an increased risk for obesity. In contrast, super-induction of the inflammation activity leads to weight loss and malnutrition in cancer cachexia. In summary, inflammation is a critical component in the maintenance of energy balance in the body. Literature is reviewed in above fields to support this view.

  19. Enhanced ZAG production by subcutaneous adipose tissue is linked to weight loss in gastrointestinal cancer patients.

    Science.gov (United States)

    Mracek, T; Stephens, N A; Gao, D; Bao, Y; Ross, J A; Rydén, M; Arner, P; Trayhurn, P; Fearon, K C H; Bing, C

    2011-02-01

    Profound loss of adipose tissue is a hallmark of cancer cachexia. Zinc-α2-glycoprotein (ZAG), a recently identified adipokine, is suggested as a candidate in lipid catabolism. In the first study, eight weight-stable and 17 cachectic cancer patients (weight loss 5% in previous 6 months) were recruited. Zinc-α2-glycoprotein mRNA and protein expression were assessed in subcutaneous adipose tissue (SAT), subcutaneous adipose tissue morphology was examined and serum ZAG concentrations were quantified. In the second cohort, ZAG release by SAT was determined in 18 weight-stable and 15 cachectic cancer patients. The effect of ZAG on lipolysis was evaluated in vitro. Subcutaneous adipose tissue remodelling in cancer cachexia was evident through shrunken adipocytes with increased fibrosis. In cachectic cancer patients, ZAG mRNA was upregulated (2.7-fold, P=0.028) while leptin mRNA decreased (2.2-fold, P=0.018); serum ZAG levels were found to be unaffected. Zinc-α2-glycoprotein mRNA correlated positively with weight loss (r=0.51, P=0.01) and serum glycerol levels (r=0.57, P=0.003). Zinc-α2-glycoprotein release by SAT was also elevated in cachectic patients (1.5-fold, P=0.024) and correlated with weight loss (r=0.50, P=0.003). Recombinant ZAG stimulated lipolysis in human adipocytes. Zinc-α2-glycoprotein expression and secretion by adipose tissue is enhanced in cachectic cancer patients. Given its lipid-mobilising effect, ZAG may contribute to adipose atrophy associated with cancer cachexia in human beings.

  20. Ghrelin Partially Protects Against Cisplatin-Induced Male Murine Gonadal Toxicity in a GHSR-1a-Dependent Manner1

    Science.gov (United States)

    Whirledge, Shannon D.; Garcia, Jose M.; Smith, Roy G.; Lamb, Dolores J.

    2015-01-01

    ABSTRACT The chemotherapeutic drug cisplatin causes a number of dose-dependent side effects, including cachexia and testicular damage. Patients receiving a high cumulative dose of cisplatin may develop permanent azoospermia and subsequent infertility. Thus, the development of chemotherapeutic regimens with the optimal postsurvival quality of life (fertility) is of high importance. This study tested the hypothesis that ghrelin administration can prevent or minimize cisplatin-induced testicular damage and cachexia. Ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR-1a), are expressed and function in the testis. Targeted deletion of ghrelin, or its receptor, significantly increases the rate of cell death in the testis, suggesting a protective role. Intraperitoneal administration of vehicle, ghrelin, or cisplatin alone or in combination with ghrelin, in cycles of 9 or 18 days, to adult male C57Bl/6 mice was performed. Body weight was measured daily and testicular and epididymal weight, sperm density and motility, testicular histology, and testicular cell death were analyzed at the time of euthanization. Ghrelin coadministration decreased the severity of cisplatin-induced cachexia and gonadal toxicity. Body, testicular, and epididymal weights significantly increased as testicular cell death decreased with ghrelin coadministration. The widespread damage to the seminiferous epithelium induced by cisplatin administration was less severe in mice simultaneously treated with ghrelin. Furthermore, ghrelin diminished the deleterious effects of cisplatin on testis and body weight homeostasis in wild-type but not Ghsr−/− mice, showing that ghrelin's actions are mediated via GHSR. Ghrelin or more stable GHSR agonists potentially offer a novel therapeutic approach to minimize the testicular damage that occurs after gonadotoxin exposure. PMID:25631345

  1. EVALUATION OF THE ANTITUMOR AND ANTICACHEXIA ACTIVITY OF GRATIOLA OFFICINALIS L. EXTRACT IN RATS WITH TRANSPLANTED SARCOMA 45

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    N. A. Navolokin

    2016-01-01

    Full Text Available Cachexia is a severe complication of cancer and currently there are no drugs that would effectively deal with exhaustion and intoxication in various diseases.Materials and methods. In this paper a study and evaluation of the antitumor and anticachexia activities of the extract of Gratiola officinalis l. in rats with transplanted sarcoma 45 in experiment in vivo was conducted. Gratiola officinalis l. extract is received by patented method and is not toxic to animals. The study was conducted on 40 white male rats line Wistar weighing 150 ± 50 g. Animals were divided into 4 groups (10 rats per group: control group, comparison group with sarcoma without affecting, group with sarcoma with intramuscular and group with sarcoma with oral administration of the extract in a dosage of 110 mg/kg. The extract was administered intramuscularly or orally 72 hours after transplantation of sarcoma 45. The tumor volume and the weight of the animals were assessed daily.Results. The extract of leaves and flowers of Gratiola officinalis l. obtained by patented method has a strong antitumor activity, reducing the growth rate of the tumor and causing marked changes in the tumor, as well as providing stable anticachexia effect. Index of tumor weight inhibition was 70.6 % on average. Intramuscular administration was more effective in reducing of tumor growth, but less effectively increases the weight of animals than oral administration. In both administration methods Gratiola officinalis extract has no toxic effect on peripheral blood. We have previously found that the extract has antioxidant activity so that anticachexia effect is pathogenic, meaning it occurs by reducing toxicity.Conclusions. Gratiola officinalis extract has a broad spectrum of biological activity, in particular antitumor, anticachexia, it is not toxic, so it is advisable to investigate as a promising tool for the treatment of tumor diseases and cancer cachexia, and cachexia caused by other chronic

  2. Nutrition Support for Persistent Inflammation, Immunosuppression, and Catabolism Syndrome.

    Science.gov (United States)

    Moore, Frederick A; Phillips, Stuart M; McClain, Craig J; Patel, Jayshil J; Martindale, Robert G

    2017-04-01

    Despite tremendous advances in critical care, multiple-organ failure continues to be a significant problem. However, in recent years, far fewer patients with multiple-organ failure die early, but many experience ongoing immune dysregulation and are developing persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Most PICS patients are discharged to nonhome destinations, fail to rehabilitate, and succumb to indolent death. From a nutrition perspective, patients with PICS experience persistent inflammation-induced cachexia despite evidenced-based recommended intensive care unit nutrition support. Recent basic and translational research indicates that prolonged expansion of myeloid-derived suppressor cells plays a central role in the pathogenesis of PICS. Myeloid-derived suppressor cells express arginase 1, which depletes arginine, causing immunosuppression and impaired wound healing. This is the rationale for arginine supplementation in PICS. Other nutrition support recommendations for PICS are based on inferences made from other patient populations who experience similar persistent inflammation-induced cachexia. These include patients with established cancers, major burns, and sarcopenia. These patients experience anabolic resistance, but studies show that this can be overcome by providing higher levels of protein and certain specific amino acids. Nutrition support guidelines recommend provision of >1.5 g/kg/d of protein and indicate that higher levels may be needed. Protein composition is also important. There is good evidence that leucine can promote anabolism in patients with cancer and sarcopenia. Finally, anabolic interventions-including intensive insulin, oxandrolone, propranolol, and resistance exercise-have proven to be effective in patients with major burns and are likely relevant in combating PICS cachexia.

  3. An adult case of Cockayne syndrome without sclerotic angiopathy.

    Science.gov (United States)

    Inoue, T; Sano, N; Ito, Y; Matsuzaki, Y; Okauchi, Y; Kondo, H; Horiuchi, N; Nakao, K; Iwata, M

    1997-08-01

    We report an autopsy case of Cockayne syndrome (CS). A 40-year-old Japanese woman was admitted to our hospital for cachexia. She had displayed the striking features of CS, including dwarfism, mental retardation, neural deafness, ataxia, intracranial calcifications, and progeria since her childhood. Endocrinological examinations suggested normal pituitary function and a disorder of the hypothalamus or the cerebrum. She died of acute pneumonia at the age of 42. Autopsy findings showed typical abnormalities in the central nervous system compatible with CS; however, no atherosclerotic change was observed in the systemic arteries.

  4. The complete control of glucose level utilizing the composition of ketogenic diet with the gluconeogenesis inhibitor, the anti-diabetic drug metformin, as a potential anti-cancer therapy.

    Science.gov (United States)

    Oleksyszyn, Józef

    2011-08-01

    In the animal models of glucose dependent cancer growth, the growth is decreased 15-30% through the use of low-carbohydrate, calorically restricted and/or ketogenic diet. The remaining growth depends on glucose formed by the liver-kidney gluconeogenesis as is the case in the cancer cachexia. It is hypothesized that a new treatment for cancer diseases should be explored which includes the ketogenic diet combined with the inhibition of gluconeogenesis by the anti-diabetic drug metformin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Reconstruction of Peripelvic Oncologic Defects.

    Science.gov (United States)

    Weichman, Katie E; Matros, Evan; Disa, Joseph J

    2017-10-01

    After studying this article, the participant should be able to: 1. Understand the anatomy of the peripelvic area. 2. Understand the advantages and disadvantages of performing peripelvic reconstruction in patients undergoing oncologic resection. 3. Select the appropriate local, pedicled, or free-flap reconstruction based on the location of the defect and donor-site characteristics. Peripelvic reconstruction most commonly occurs in the setting of oncologic ablative surgery. The peripelvic area contains several distinct reconstructive regions, including vagina, vulva, penis, and scrotum. Each area provides unique reconstructive considerations. In addition, prior or future radiation therapy or chemotherapy along with cancer cachexia can increase the complexity of reconstruction.

  6. Anorexia in human and experimental animal models: physiological aspects related to neuropeptides.

    Science.gov (United States)

    Yoshimura, Mitsuhiro; Uezono, Yasuhito; Ueta, Yoichi

    2015-09-01

    Anorexia, a loss of appetite for food, can be caused by various physiological and pathophysiological conditions. In this review, firstly, clinical aspects of anorexia nervosa are summarized in brief. Secondly, hypothalamic neuropeptides responsible for feeding regulation in each hypothalamic nucleus are discussed. Finally, three different types of anorexigenic animal models; dehydration-induced anorexia, cisplatin-induced anorexia and cancer anorexia-cachexia, are introduced. In conclusion, hypothalamic neuropeptides may give us novel insight to understand and find effective therapeutics strategy essential for various kinds of anorexia.

  7. Leptin: regulatory role in bone metabolism and in flogosis

    Directory of Open Access Journals (Sweden)

    G.D. Ferraccioli

    2011-09-01

    Full Text Available Leptin is a peptidic molecule synthesized almost exclusively by adipocytes, that regulates appetite and energy expenditure at the hypothalamic level. In the last few years, further actions have been attributed to this molecule, as modulating the immune response and affecting the bone metabolism. We have reviewed if leptin contributes to the metabolic changes leading to cachexia and to the regulation of flogosis, paying attention to the pathogenetic mechanisms of cronic arthritis. Besides, considering the relationship between body mass index (BMI e bone mineral density (BMD and the protective role of the obesity towards osteoporosis, we have analysed the role of leptin on the bone metabolism

  8. The impact of weight loss on patients with cancer.

    Science.gov (United States)

    Escamilla, Danilo Macasa; Jarrett, Patricia

    Weight loss due to cachexia is a common symptom in patients with advanced cancer and often affects their quality of life. This article outlines a literature review conducted to better understand the effects of weight loss on patients with cancer. Five themes were identified that encompassed patients' experiences, including personal response, physical effects, emotions and moods, changes in eating habits and effects on social life. The review suggests strategies that health professionals can implement to ensure patients' and their families' feelings about weight loss are taken into consideration.

  9. Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1.

    Science.gov (United States)

    McDonald, Merry-Lynn Noelle; Won, Sungho; Mattheisen, Manuel; Castaldi, Peter J; Cho, Michael H; Rutten, Erica; Hardin, Megan; Yip, Wai-Ki; Rennard, Stephen I; Lomas, David A; Wouters, Emiel F M; Agusti, Alvar; Casaburi, Richard; Lange, Christoph P; O'Connor, George; Hersh, Craig P; Silverman, Edwin K

    2017-06-01

    There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years of age with three consecutive BMI time points (n = 4162). Four GWAS of ΔBMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418 365 single-nucleotide polymorphisms (SNPs). Two SNPs reached a level of genome-wide significance (P < 5 × 10 -8 ) with ΔBMI: (i) rs41526344 within the CNTN4 gene, among COPD cases (β = 0.13, P = 4.3 × 10 -8 ); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (DOCK1) among GI cancer cases (β = 0.10, P = 1.9 × 10 -8 ). The DOCK1 SNP association replicated in the ΔBMI GWAS among COPD cases (β meta-analyis  = 0.10, P meta-analyis  = 9.3 × 10 -10 ). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion. In sum, one statistically significant common variant in the DOCK1 gene was associated with ΔBMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ΔBMI in complex diseases. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  10. Cryptosporidium varanii infection in leopard geckos (Eublepharis macularius in Argentina

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    A. Dellarupe

    2016-06-01

    Full Text Available Cryptosporidiosis is observed in reptiles with high morbidity and considerable mortality. The objective of this study was to achieve the molecular identification of Cryptosporidium spp. in pet leopard geckos (Eublepharis macularius from a breeder colony in Buenos Aires, Argentina. Oocysts comparable to those of Cryptosporidium spp. were detected in three geckos with a history of diarrhea, anorexia and cachexia. Molecular identification methods confirmed the presence of Cryptosporidium varanii (syn. C. saurophilum. This agent was considered to be the primary cause of the observed clinical disease. This is the first description of C. varanii infection in pet reptiles in Argentina.

  11. Epigenetics of cancer-associated muscle catabolism.

    Science.gov (United States)

    Carr, Ryan M; Enriquez-Hesles, Elisa; Olson, Rachel Lo; Jatoi, Aminah; Doles, Jason; Fernandez-Zapico, Martin E

    2017-09-25

    Cancer patients are commonly affected by cachexia, a wasting process involving muscle and fat. Specifically, loss of the muscle compartment has been associated with poor prognosis and suboptimal response to therapy. Nutritional support has been ineffective in treating this process leading to investigations into the underlying molecular processes governing muscle catabolism. In this commentary, we discuss the molecular mechanisms of cancer-associated muscle metabolism and the epigenetic processes responsible for the muscle wasting phenotype. Ultimately, we highlight how the epigenome may serve as a promising therapeutic target in reversing cancer-associated muscle catabolism.

  12. Tuberculosis, bronchiectasis, and infertility: what ailed George Orwell?

    Science.gov (United States)

    Ross, John J

    2005-12-01

    In the last and most productive years of his life, George Orwell struggled with pulmonary tuberculosis, dying at the dawn of the era of chemotherapy. His case history illustrates clinical aspects of tuberculosis with contemporary relevance: the role of poverty in its spread, the limited efficacy of monotherapy, the potential toxicity of treatment, and the prominence of cachexia as a terminal symptom. Orwell's ordeals with collapse therapy may have influenced the portrayal of the tortures of Winston Smith in the novel 1984. I discuss unifying diagnoses for Orwell's respiratory problems and apparent infertility, including tuberculous epididymitis, Young syndrome, immotile cilia syndrome, and cystic fibrosis.

  13. Fluorosis of cattle in the Wroclaw province

    Energy Technology Data Exchange (ETDEWEB)

    Bohosiewicz, M.; Jopek, Z.

    1975-01-01

    Fluorosis of cattle and sheep was diagnosed in the neighborhood of glassworks and a superphosphate mill. In cows there was a brown color and loss of the enamel on incisive teeth, uneven detrition of molar teeth, osseous lesions in teeth and limb bones, and in some animals also swelling and painfulness of limb joints, hobble and cachexia. In sheep the lesions were observed in teeth only. Exacerbation of the lesions in the animals coming from the neighborhood of the glass works was greater than in those coming from the neighborhood of the superphosphate mill. There was found no relation between exacerbation of the lesions in teeth and bones.

  14. Palliative Care for Dementia.

    Science.gov (United States)

    Stewart, Jonathan T; Schultz, Susan K

    2018-03-01

    With the growing care needs for the older population at the end of their lives, there has been a substantial increase in attention to the management of the patient with dementia in hospice and palliative care services. This article reviews issues in access to care and the optimal management of the patient with dementia, particularly in the context of neuropsychiatric complexities. Special issues such as delirium, cachexia, behavioral symptoms, and pain management are addressed. Future challenges in research such as the development of better prognostic models are noted as well as the importance of attention to access to care. Published by Elsevier Inc.

  15. Cancer anorexia: hypothalamic activity and its association with inflammation and appetite-regulating peptides in lung cancer.

    Science.gov (United States)

    Molfino, Alessio; Iannace, Alessandro; Colaiacomo, Maria Chiara; Farcomeni, Alessio; Emiliani, Alessandra; Gualdi, Gianfranco; Laviano, Alessandro; Rossi Fanelli, Filippo

    2017-02-01

    Energy homeostasis is mediated by the hypothalamus, whose inflammation-induced functional derangements contribute to the onset of anorexia in cancer. By using functional magnetic resonance imaging (fMRI), we determined the patterns of hypothalamic activation after oral intake in anorexic (A), non-anorexic (NA) cancer patients, and in controls (C). Lung cancer patients were considered. Hypothalamic activation was recorded in A and NA patients and in C by fMRI, before (T0), immediately after (T1) the administration of an oral nutritional supplement, and after 15 min (T2). The grey of the hypothalamus and Blood Oxygen Level Dependent (BOLD) intensity were calculated and normalized for basal conditions. Interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, ghrelin, and leptin plasma levels were measured. A statistical parametric mapping was used. Thirteen lung cancer patients (7 M, 6 F; 9A, 4NA) and 2 C (1 M, 1 F) were enrolled. Controls had the lowest BOLD intensity. At all-time points, anorexic patients showed lower hypothalamic activity compared with NA (P anorexia, BOLD signals modification before and after oral challenge correlated with basal values of IL-1 and ghrelin (P anorexia, before, and after oral intake. © 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  16. The relationship among acute-phase response proteins, cytokines and hormones in cachectic patients with colon cancer

    Directory of Open Access Journals (Sweden)

    Dulger Ahmet

    2010-09-01

    Full Text Available Abstract Backgraund Acute-phase response proteins (APRP, cytokines and hormones have been claimed to be an independent prognostic factor of malignancies, however the basis for their association with prognosis remains unexplained. We suggest that in colon malignancies, as similar to pancreatic and lung cancers, changes in APRP are associated with angiogenesis. Methods C-reactive protein (CRP, albumin, IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, midkine, VEGF-A, VEGF-C, leptin, adiponectin, and ghrelin serum levels are studied in 126 colon cancer patients and 36 healthy subjects. Results We found statistically significant difference and correlations between two groups. We found significantly higher serum CRP, IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, VEGF-A, VEGF-C and leptin concentrations in patients relative to controls (p Conclusions Cachexia in patients with colon cancers is associated with changes in APRP, cytokines and hormone concentrations. These biomarkers and cachexia together have a direct relationship with accelerated angiogenesis. This may lead to a connection between the outcomes in malignancies and the biomarkers.

  17. Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by ERK inhibition.

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    Fabio Penna

    Full Text Available BACKGROUND: The onset of cachexia is a frequent feature in cancer patients. Prominent characteristic of this syndrome is the loss of body and muscle weight, this latter being mainly supported by increased protein breakdown rates. While the signaling pathways dependent on IGF-1 or myostatin were causally involved in muscle atrophy, the role of the Mitogen-Activated-Protein-Kinases is still largely debated. The present study investigated this point on mice bearing the C26 colon adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: C26-bearing mice display a marked loss of body weight and muscle mass, this latter associated with increased phosphorylated (p-ERK. Administration of the ERK inhibitor PD98059 to tumor bearers attenuates muscle depletion and weakness, while restoring normal atrogin-1 expression. In C26 hosts, muscle wasting is also associated with increased Pax7 expression and reduced myogenin levels. Such pattern, suggestive of impaired myogenesis, is reversed by PD98059. Increased p-ERK and reduced myosin heavy chain content can be observed in TNFα-treated C2C12 myotubes, while decreased myogenin and MyoD levels occur in differentiating myoblasts exposed to the cytokine. All these changes are prevented by PD98059. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that ERK is involved in the pathogenesis of muscle wasting in cancer cachexia and could thus be proposed as a therapeutic target.

  18. Central melanocortins and the regulation of weight during acute and chronic disease.

    Science.gov (United States)

    Marks, D L; Cone, R D

    2001-01-01

    Recent advances in our understanding of the regulation of body weight, appetite, and metabolic rate have highlighted the role of the adipose-derived hormone leptin and its receptor as fundamental modulators of these processes. Investigations of the neural targets for leptin action--as well as characterization of the agouti obesity syndrome--have, in turn, led to the discovery of fundamental neural pathways involved in the central regulation of energy homeostasis. In particular, the central melanocortin system has been shown to regulate appetite and metabolic rate in rodents; mutations in this system have been demonstrated to result in obesity in humans. Overall, the melanocortin system appears to function as a bidirectional rheostat in the regulation of energy intake and expenditure in rodents and potentially in humans. The first section of this chapter will focus on the development of our understanding of melanocortin physiology in the context of obesity. In particular, recent data regarding the interplay between melanocortin and neuropeptide Y (NPY) signaling at a cellular level will be discussed. The following section will discuss the hypothesis that melanocortin signaling plays a role in pathological weight loss and hypermetabolism observed in murine cachexia models. The potential role of this system in integrating a variety of anorexic and cachexic signals, as well as the potential for its pharmacological manipulation in the treatment of human cachexia, will be discussed.

  19. Evaluation of Weight Change During Carboplatin Therapy in Dogs With Appendicular Osteosarcoma.

    Science.gov (United States)

    Story, A L; Boston, S E; Kilkenny, J J; Singh, A; Woods, J P; Culp, W T N; Skorupski, K A; Lu, X

    2017-07-01

    The prevalence of cancer cachexia in veterinary medicine has not been studied widely, and as of yet, no definitive diagnostic criteria effectively assess this syndrome in veterinary patients. (1) To determine the patterns of weight change in dogs with appendicular osteosarcoma treated with amputation and single-agent carboplatin during the course of adjuvant chemotherapy; and (2) to determine whether postoperative weight change is a negative prognostic indicator for survival time in dogs with osteosarcoma. Eighty-eight dogs diagnosed with appendicular osteosarcoma. Animals were accrued from 3 veterinary teaching hospitals. Retrospective, multi-institutional study. Dogs diagnosed with appendicular osteosarcoma and treated with limb amputation followed by a minimum of 4 doses of single-agent carboplatin were included. Data analyzed in each patient included signalment, tumor site, preoperative serum alkaline phosphatase activity (ALP), and body weight (kg) at each carboplatin treatment. A slight increase in weight occurred over the course of chemotherapy, but this change was not statistically significant. Weight change did not have a significant effect on survival. Institution, patient sex, and serum ALP activity did not have a significant effect on survival. Weight change was not a prognostic factor in these dogs, and weight loss alone may not be a suitable method of determining cancer cachexia in dogs with appendicular osteosarcoma. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  20. Endogenous lipoid pneumonia in a cachectic patient after brain injury.

    Science.gov (United States)

    Zhang, Ji; Mu, Jiao; Lin, Wei; Dong, Hongmei

    2015-01-01

    Endogenous lipoid pneumonia (EnLP) is an uncommon non-life-threatening inflammatory lung disease that usually occurs in patients with conditions such as lung cancers, primary sclerosing cholangitis, and undifferentiated connective tissue disease. Here we report a case of EnLP in a paralytic and cachectic patient with bronchopneumonia after brain injury. A 40-year-old man experienced a severe brain injury in an automobile accident. He was treated for 1 month and his status plateaued. However, he became paralyzed and developed cachexia and ultimately died 145 days after the accident. Macroscopically, multifocal yellowish firm nodules were visible on scattered gross lesions throughout the lungs. Histologically, many foam cells had accumulated within the alveoli and alveolar walls accompanied by a surrounding interstitial infiltration of lymphocytes. The findings were in accordance with a diagnosis of EnLP. Bronchopneumonia was also noted. To our knowledge, there have been few reports of EnLP associated with bronchopneumonia and cachexia after brain injury. This uncommon pathogenesis should be well recognized by clinicians and forensic pathologists. The case reported here should prompt medical staff to increase the nutritional status and fight pulmonary infections in patients with brain injury to prevent the development of EnLP.

  1. Serum Levels of Resistin, Adiponectin, and Apelin in Gastroesophageal Cancer Patients

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    Dorota Diakowska

    2014-01-01

    Full Text Available The aim of the study was the investigation of relationship between cachexia syndrome and serum resistin, adiponectin, and apelin in patients with gastroesophageal cancer (GEC. Material and Methods. Adipocytokines concentrations were measured in sera of 85 GEC patients and 60 healthy controls. They were also evaluated in tumor tissue and appropriate normal mucosa of 38 operated cancer patients. Results. Resistin and apelin concentrations were significantly higher in GEC patients than in the controls. The highest resistin levels were found in cachectic patients and in patients with distant metastasis. Serum adiponectin significantly decreased in GEC patients with regional and distant metastasis. Serum apelin was significantly higher in cachectic patients than in the controls. Apelin was positively correlated with hsCRP level. Resistin and apelin levels increased significantly in tumor tissues. Weak positive correlations between adipocytokines levels in serum and in tumor tissue were observed. Conclusions. Resistin is associated with cachexia and metastasis processes of GEC. Reduction of serum adiponectin reflects adipose tissue wasting in relation to GEC progression. Correlation of apelin with hsCRP can reflect a presumable role of apelin in systemic inflammatory response in esophageal and gastric cancer.

  2. The final word on nutritional screening and assessment in older persons.

    Science.gov (United States)

    Cereda, Emanuele; Veronese, Nicola; Caccialanza, Riccardo

    2017-10-14

    To provide an updated perspective of how nutritional screening and assessment in older persons should be performed and reasonably implemented in the near future. Although nutritional screening and assessment should be fast and easy procedures, there is increasing evidence that more time should be dedicated to them. This is probably an answer to the claim to a medicine being more preventive than curative. Increasing interest is currently given to healthy aging and nutritional status is more likely to be addressed for its implications on functional status and disability. Important prognostic conditions, such as frailty, sarcopenia, and cachexia, which are closely linked to the nutritional domain, are at the top of the agenda. Therefore, body composition is a key issue and functional status is suggested as primary endpoint of nutrition trials. In this scenario, there is also a rationale for systematic assessment of inflammation, protein intake, and vitamin D status as potential contributing factors to reduced muscle mass and function. A 'second-generation' multidimensional nutritional screening and assessment including the evaluation of body composition, frailty, sarcopenia, and cachexia could be hypothesized. Nutritional assessment should be also completed by the systematic evaluation of inflammation, protein intake, and vitamin D status.

  3. Sarcopenia With Limited Mobility: An International Consensus

    Science.gov (United States)

    Morley, John E.; Abbatecola, Angela Marie; Argiles, Josep M.; Baracos, Vickie; Bauer, Juergen; Bhasin, Shalender; Cederholm, Tommy; Stewart Coats, Andrew J.; Cummings, Steven R.; Evans, William J.; Fearon, Kenneth; Ferrucci, Luigi; Fielding, Roger A.; Guralnik, Jack M.; Harris, Tamara B.; Inui, Akio; Kalantar-Zadeh, Kamyar; Kirwan, Bridget-Anne; Mantovani, Giovanni; Muscaritoli, Maurizio; Newman, Anne B.; Rossi-Fanelli, Filippo; Rosano, Giuseppe M. C.; Roubenoff, Ronenn; Schambelan, Morris; Sokol, Gerald H.; Storer, Thomas W.; Vellas, Bruno; von Haehling, Stephan; Yeh, Shing-Shing; Anker, Stefan D.

    2016-01-01

    A consensus conference convened by the Society of Sarcopenia, Cachexia and Wasting Disorders has concluded that “Sarcopenia, ie, reduced muscle mass, with limited mobility” should be considered an important clinical entity and that most older persons should be screened for this condition. “Sarcopenia with limited mobility” is defined as a person with muscle loss whose walking speed is equal to or less than 1 m/s or who walks less than 400 m during a 6-minute walk, and who has a lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean of healthy persons between 20 and 30 years of age of the same ethnic group. The limitation in mobility should not clearly be a result of otherwise defined specific diseases of muscle, peripheral vascular disease with intermittent claudication, central and peripheral nervous system disorders, or cachexia. Clinically significant interventions are defined as an increase in the 6-minute walk of at least 50 meters or an increase of walking speed of at least 0.1 m/s. “A word is not a crystal, transparent and unchanged; it is the skin of a living thought and may vary greatly in color and content according to the circumstances and the time when it is used.”—Oliver Wendell Holmes PMID:21640657

  4. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN - a randomized multicentre trial

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    Kraft Matthias

    2012-07-01

    Full Text Available Abstract Background Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia. Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM kg. During treatment body-mass-index increased by 3,4 ± 1,4% under L-Carnitine and decreased (−1,5 ± 1,4% in controls (p  Conclusion While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine.

  5. A framework for prescription in exercise-oncology research.

    Science.gov (United States)

    Sasso, John P; Eves, Neil D; Christensen, Jesper F; Koelwyn, Graeme J; Scott, Jessica; Jones, Lee W

    2015-06-01

    The field of exercise-oncology has increased dramatically over the past two decades, with close to 100 published studies investigating the efficacy of structured exercise training interventions in patients with cancer. Of interest, despite considerable differences in study population and primary study end point, the vast majority of studies have tested the efficacy of an exercise prescription that adhered to traditional guidelines consisting of either supervised or home-based endurance (aerobic) training or endurance training combined with resistance training, prescribed at a moderate intensity (50-75% of a predetermined physiological parameter, typically age-predicted heart rate maximum or reserve), for two to three sessions per week, for 10 to 60 min per exercise session, for 12 to 15 weeks. The use of generic exercise prescriptions may, however, be masking the full therapeutic potential of exercise treatment in the oncology setting. Against this background, this opinion paper provides an overview of the fundamental tenets of human exercise physiology known as the principles of training, with specific application of these principles in the design and conduct of clinical trials in exercise-oncology research. We contend that the application of these guidelines will ensure continued progress in the field while optimizing the safety and efficacy of exercise treatment following a cancer diagnosis. © 2015 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society of Sarcopenia, Cachexia and Wasting Disorders.

  6. Expression of TRAF6 and ubiquitin mRNA in skeletal muscle of gastric cancer patients

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    Sun Yuan-Shui

    2012-09-01

    Full Text Available Abstract Objective To investigate the prognostic significance of tumor necrosis factor receptor (TNFR,-associated factor 6 (TRAF6,-and ubiquitin in gastric cancer patients. Methods Biopsies of the rectus abdominis muscle were obtained intra operatively from 102 gastric cancer patients and 29 subjects undergoing surgery for benign abdominal diseases, and muscle TRAF6 and ubiquitin mRNA expression and proteasome proteolytic activities were assessed. Results TRAF6 was significantly upregulated in muscle of gastric cancer compared with the control muscles. TRAF6 was upregulated in 67.65% (69/102 muscle of gastric cancer. Over expression of TRAF6 in muscles of gastric cancer were associated with TNM stage, level of serum albumin and percent of weight loss. Ubiquitin was significantly upregulated in muscle of gastric cancer compared with the control muscles. Ubiquitin was upregulated in 58.82% (60/102 muscles of gastric cancer. Over expression of ubiquitin in muscles of gastric cancer were associated with TNM (Tumor-Node-Metastasis stage and weight loss. There was significant relation between TRAF6 and ubiquitin expression. Conclusions We found a positive correlation between TRAF6 and ubiquitin expression, suggesting that TRAF6 may up regulates ubiquitin activity in cancer cachexia. While more investigations are required to understand its mechanisms of TRAF6 and ubiquitin in skeletal muscle. Correct the catabolic-anabolic imbalance is essential for the effective treatment of cancer cachexia.

  7. Fish oil-supplementation increases appetite in healthy adults

    DEFF Research Database (Denmark)

    Damsbo-Svendsen, Signe; Rønsholdt, Mia Dybkjær; Lauritzen, Lotte

    2013-01-01

    Marine n-3 fatty acids are hypothesized to have beneficial effects on obesity and cancer cachexia possibly via an effect on appetite. The aim of this study was to investigate, if fish oil-supplementation affects appetite in healthy individuals. In a randomized cross-over study, 20 normal-weight s......Marine n-3 fatty acids are hypothesized to have beneficial effects on obesity and cancer cachexia possibly via an effect on appetite. The aim of this study was to investigate, if fish oil-supplementation affects appetite in healthy individuals. In a randomized cross-over study, 20 normal...... with the paired design considering oil sequence and gender. All subjects completed both periods with a compliance of 96% and oil sequence did not affect the results. There was no difference between the two supplements in any pre-breakfast appetite scores, but the post-prandial sensation of being full was 1.21. cm...... (0.20; 2.22) lower after the fish oil-period. Furthermore, there was a supplement × gender-interaction on "desire to eat more" due to a score increase of 1.09. cm (0.28; 1.90) in women only. These results suggest that marine n-3 fatty acid may increase appetite. This finding would be potentially...

  8. Multimodal management as requirement for the clinical use of anticachexia drugs - a regulatory and a clinical perspective.

    Science.gov (United States)

    Borg, John J; Anker, Stefan D; Rosano, Giuseppe; Serracino-Inglott, Anthony; Strasser, Florian

    2015-12-01

    Multimodal management has been proposed as key to any effective drug intervention in cachexia. This article attempts to reflect on clinical and regulatory considerations of multimodal management treatment as a regulatory requirement in anticachexia drug therapy. To date, no European Union (EU) regulatory guidelines have been published and therefore this review could attempt to present and discuss some central issues to consider when developing an anticachexia drug. The following themes are considered: EU regulatory pathways for drug approval (conditional and exceptional circumstances as well as adaptive licensing); selection criteria for randomized clinical trials allowing the identification and characterization of the population of interest that is an at-risk population with undisputable clinical need; issues related to primary and secondary outcome measures that are adequate to determine the efficacy of the intervention and the approach for the development of clinical biomarkers for cachexia. Conversely, the incorporation of multimodal treatment in anticachexia drug therapy is expected to increase the effectiveness of intervention. This aspect is the aspect that appeals to pharmaceutical companies; however, at the same time, this raises regulatory and clinical issues that need to be kept in mind when designing randomised clinical trials.

  9. Effect of acupuncture for radioactive-iodine-induced anorexia in thyroid cancer patients: a randomized, double-blinded, sham-controlled pilot study.

    Science.gov (United States)

    Jeon, Ju-Hyun; Yoon, Jeungwon; Cho, Chong-Kwan; Jung, In-Chul; Kim, Sungchul; Lee, Suk-Hoon; Yoo, Hwa-Seung

    2015-05-01

    The aim of this study is to evaluate the efficacy and safety of acupuncture for radioactive iodine (RAI)-induced anorexia in thyroid cancer patients. Fourteen thyroid cancer patients with RAI-induced anorexia were randomized to a true acupuncture or sham acupuncture group. Both groups were given 6 true or sham acupuncture treatments in 2 weeks. Outcome measures included the change of the Functional Assessment of Anorexia and Cachexia Treatment (FAACT; Anorexia/Cachexia Subscale [ACS], Functional Assessment of Cancer Therapy-General [FACT-G]), Visual Analogue Scale (VAS), weight, body mass index (BMI), ACTH, and cortisol levels. The mean FAACT ACS scores of the true and sham acupuncture groups increased from baseline to exit in intention-to-treat (ITT) and per protocol (PP) analyses; the true acupuncture group showed higher increase but with no statistical significance. Between groups, from baseline to the last treatment, statistically significant differences were found in ITT analysis of the Table of Index (TOI) score (P = .034) and in PP analysis of the TOI (P = .016), FACT-G (P = .045), FAACT (P = .037) scores. There was no significant difference in VAS, weight, BMI, ACTH, and cortisol level changes between groups. Although the current study is based on a small sample of participants, our findings support the safety and potential use of acupuncture for RAI-induced anorexia and quality of life in thyroid cancer patients. © The Author(s) 2015.

  10. A Dog with Multiple Infections of Enteric Parasitic Zoonosis in Mashhad City, North-East of Iran; a Case Report

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    Mohaghegh M.A. PhD,

    2016-03-01

    Full Text Available Abstract Aims: In this study, we examined stool specimen from a 3-year-old domesticated dog, which was referred to a veterinary clinic with clinical signs such as nausea or vomiting, dysentery, cachexia and rash in Mashhad city, northeast of Iran. Patient & Methods: A 3-year-old pet dog was referred to veterinary clinic of Mashhad in February 2016 by symptoms including, nausea or vomiting, dysentery, cachexia and rash in Mashhad City, Northeast of Iran. For parasitological examination, formalin-ether concentration technique was used. Fecal smears were made from the sediment, stained with iodine and observed by light microscope. Modified Ziehl Neelsen method was used for the detection of Cryptosporidium spp. Findings: The animal was infected with 10 disease-causing parasites; Taenia spp., Fasciola spp., Dicrocoelium dendriticum, Acanthocephal spp., Trichuris vulpis, Hook worm, Giardia spp., Blastocystis spp., Eimeria spp., and Cystoisospora spp. Conclusion: Domestic and stray dog could be an important sources for distribution of zoonoses disease especially parasitic agents.

  11. The ghrelin axis--does it have an appetite for cancer progression?

    Science.gov (United States)

    Chopin, Lisa K; Seim, Inge; Walpole, Carina M; Herington, Adrian C

    2012-12-01

    Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHSR), is a peptide hormone with diverse physiological roles. Ghrelin regulates GH release, appetite and feeding, gut motility, and energy balance and also has roles in the cardiovascular, immune, and reproductive systems. Ghrelin and the GHSR are expressed in a wide range of normal and tumor tissues, and a fluorescein-labeled, truncated form of ghrelin is showing promise as a biomarker for prostate cancer. Plasma ghrelin levels are generally inversely related to body mass index and are unlikely to be useful as a biomarker for cancer, but may be useful as a marker for cancer cachexia. Some single nucleotide polymorphisms in the ghrelin and GHSR genes have shown associations with cancer risk; however, larger studies are required. Ghrelin regulates processes associated with cancer, including cell proliferation, apoptosis, cell migration, cell invasion, inflammation, and angiogenesis; however, the role of ghrelin in cancer is currently unclear. Ghrelin has predominantly antiinflammatory effects and may play a role in protecting against cancer-related inflammation. Ghrelin and its analogs show promise as treatments for cancer-related cachexia. Further studies using in vivo models are required to determine whether ghrelin has a role in cancer progression.

  12. Dietetic and Psychological Mindfulness Workshops for the Management of Cachectic Cancer Patients. A Randomized Study.

    Science.gov (United States)

    Focan, Christian; Houbiers, Ghislain; Gilles, Laura; Van Steeland, Tiphany; Georges, Nadine; Maniglia, Alexandro; Lobelle, Jean-Pierre; Baro, Vincent; Graas, Marie-Pascale

    2015-11-01

    To determine if actively-treated cancer patients developing cachexia could benefit from participation to mindfulness workshops. Subjects developing cachexia signs while treated for cancer were randomized in a trial aiming to compare an experimental group that would participate to specific workshops based on mindfulness alternating dietetic and psychological approaches, and a control group managed in accordance to usual practice. The recruitment was difficult (12% of the approached population). Finally 53 patients accepted to participate. Despite an unpredictable compliance of workshop participants, the final satisfaction score attained 75%. In comparison with the control group, patients randomized to the experimental group showed a significant benefit with an increase of their body weight and an improvement of their WHO status score. They also experienced an improvement of emotional function and observation faculty as well as a relief of fatigue and some digestive disorders. Selected cachectic cancer patients may benefit from this experimental approach. This approach may, however, be difficult to implement on a large scale. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. Ginsenosides Rb3 and Rd reduce polyps formation while reinstate the dysbiotic gut microbiota and the intestinal microenvironment in Apc(Min/+) mice.

    Science.gov (United States)

    Huang, Guoxin; Khan, Imran; Li, Xiaoang; Chen, Lei; Leong, Waikit; Ho, Leung Tsun; Hsiao, W L Wendy

    2017-10-02

    Studies showed that manipulation of gut microbiota (GM) composition through the treatment of prebiotics could be a novel preventive measure against colorectal cancer (CRC) development. In this study, for the first time, we assessed the non-toxic doses of the triterpene saponins (ginsenoside-Rb3 and ginsenoside-Rd) - as prebiotics - that effectively reinstated the dysbiotic-gut microbial composition and intestinal microenvironment in an Apc(Min/+) mice model. Rb3 and Rd effectively reduced the size and the number of the polyps that accompanied with the downregulation of oncogenic signaling molecules (iNOS, STAT3/pSTAT3, Src/pSrc). Both the compounds improved the gut epithelium by promoting goblet and Paneth cells population and reinstating the E-cadherin and N-Cadherin expression. Mucosal immunity remodeled with increased in anti-inflammatory cytokines and reduced in pro-inflammatory cytokines in treated mice. All these changes were correlating with the promoted growth of beneficial bacteria such as Bifidobacterium spp., Lactobacillus spp., Bacteroides acidifaciens, and Bacteroides xylanisolvens. Whereas, the abundance of cancer cachexia associated bacteria, such as Dysgonomonas spp. and Helicobacter spp., was profoundly lower in Rb3/Rd-treated mice. In conclusion, ginsenosides Rb3 and Rd exerted anti-cancer effects by holistically reinstating mucosal architecture, improving mucosal immunity, promoting beneficial bacteria, and down-regulating cancer-cachexia associated bacteria.

  14. The 2014 ESPEN Arvid Wretlind Lecture: Metabolism & nutrition: Shifting paradigms in COPD management.

    Science.gov (United States)

    Schols, Annemie M W J

    2015-12-01

    COPD is a chronic disease of the lungs, but heterogeneous with respect to clinical manifestations and disease progression. This has consequences for health risk assessment, stratification and management. Heterogeneity can be driven by pulmonary events but also by systemic consequences (e.g. cachexia and muscle weakness) and co-morbidity (e.g. osteoporosis, diabetes and cardiovascular disease). This paper shows how a metabolic perspective on COPD has contributed significantly to understanding clinical heterogeneity and the need for a paradigm shift from reactive medicine towards predictive, preventive, personalized and participatory medicine. These insights have also lead to a paradigm shift in nutritional therapy for COPD from initial ignorance or focusing on putative adverse effects of carbohydrate overload on the ventilatory system to beneficial effects of nutritional intervention on body composition and physical functioning as integral part of disease management. The wider implications beyond COPD as disease have been as clinical model for translational cachexia research. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  15. Nutritional status assessment in colorectal cancer patients qualified to systemic treatment.

    Science.gov (United States)

    Ziętarska, Monika; Krawczyk-Lipiec, Joanna; Kraj, Leszek; Zaucha, Renata; Małgorzewicz, Sylwia

    2017-01-01

    Cancer is usually associated with impaired nutritional status, which is one of the factors contributing to the deterioration of the results of surgery, chemotherapy, or radiotherapy. The aim of this study was the assessment of the nutritional status of patients with CRC qualified to chemotherapy. Seventy-five persons aged 40-86 years with colorectal cancer were examined. To evaluate the nutritional status NRS 2002, SGA, SCRINIO Working Group classification, VAS scale for appetite, and FAACT questionnaire were used. The health status of patients was evaluated based on the Karnofsky Performance Scale. Anthropometric measurements were made. The results indicate that 75% of patients present pre-cachexia status based on SCRINIO Working Group classification. According to both NRS-2002 and SGA, 73.3% of patients were moderately malnourished and 2.7% were severely malnourished. 37.0% of patients had moderate appetite and 6.0% (n = 5) had poor appetite. The Karnofsky score indicates the state of normal activity, and minor signs and symptoms of the disease among most of the patients. A statistically significant positive correlation was found between the VAS and the Karnofsky score (R = 0,4; p nutritional status of patients with CRC should be a part of routine clinical practice. Because of the high incidence of confirmed pre-cachexia, this group of patients also requires early adequate nutrition intervention.

  16. Vitamin D, a modulator of musculoskeletal health in chronic kidney disease.

    Science.gov (United States)

    Molina, Pablo; Carrero, Juan J; Bover, Jordi; Chauveau, Philippe; Mazzaferro, Sandro; Torres, Pablo Ureña

    2017-10-01

    The spectrum of activity of vitamin D goes beyond calcium and bone homeostasis, and growing evidence suggests that vitamin D contributes to maintain musculoskeletal health in healthy subjects as well as in patients with chronic kidney disease (CKD), who display the combination of bone metabolism disorder, muscle wasting, and weakness. Here, we review how vitamin D represents a pathway in which bone and muscle may interact. In vitro studies have confirmed that the vitamin D receptor is present on muscle, describing the mechanisms whereby vitamin D directly affects skeletal muscle. These include genomic and non-genomic (rapid) effects, regulating cellular differentiation and proliferation. Observational studies have shown that circulating 25-hydroxyvitamin D levels correlate with the clinical symptoms and muscle morphological changes observed in CKD patients. Vitamin D deficiency has been linked to low bone formation rate and bone mineral density, with an increased risk of skeletal fractures. The impact of low vitamin D status on skeletal muscle may also affect muscle metabolic pathways, including its sensitivity to insulin. Although some interventional studies have shown that vitamin D may improve physical performance and protect against the development of histological and radiological signs of hyperparathyroidism, evidence is still insufficient to draw definitive conclusions. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  17. Role of Protein Carbonylation in Skeletal Muscle Mass Loss Associated with Chronic Conditions

    Directory of Open Access Journals (Sweden)

    Esther Barreiro

    2016-05-01

    Full Text Available Muscle dysfunction, characterized by a reductive remodeling of muscle fibers, is a common systemic manifestation in highly prevalent conditions such as chronic heart failure (CHF, chronic obstructive pulmonary disease (COPD, cancer cachexia, and critically ill patients. Skeletal muscle dysfunction and impaired muscle mass may predict morbidity and mortality in patients with chronic diseases, regardless of the underlying condition. High levels of oxidants may alter function and structure of key cellular molecules such as proteins, DNA, and lipids, leading to cellular injury and death. Protein oxidation including protein carbonylation was demonstrated to modify enzyme activity and DNA binding of transcription factors, while also rendering proteins more prone to proteolytic degradation. Given the relevance of protein oxidation in the pathophysiology of many chronic conditions and their comorbidities, the current review focuses on the analysis of different studies in which the biological and clinical significance of the modifications induced by reactive carbonyls on proteins have been explored so far in skeletal muscles of patients and animal models of chronic conditions such as COPD, disuse muscle atrophy, cancer cachexia, sepsis, and physiological aging. Future research will elucidate the specific impact and sites of reactive carbonyls on muscle protein content and function in human conditions.

  18. Reduction of splenic immunosuppressive cells and enhancement of anti-tumor immunity by synergy of fish oil and selenium yeast.

    Directory of Open Access Journals (Sweden)

    Hang Wang

    Full Text Available Growing evidence has shown that regulatory T cells (Tregs and myeloid-derived suppressor cells (MDSCs abnormally increase in cancer cachectic patients. Suppressions of Tregs and MDSCs may enhance anti-tumor immunity for cancer patients. Fish oil and selenium have been known to have many biological activities such as anti-inflammation and anti-oxidation. Whether fish oil and/or selenium have an additional effect on population of immunosuppressive cells in tumor-bearing hosts remained elusive and controversial. To gain insights into their roles on anti-tumor immunity, we studied the fish oil- and/or selenium-mediated tumor suppression and immunity on lung carcinoma, whereof cachexia develops. Advancement of cachexia in a murine lung cancer model manifested with such indicative symptoms as weight loss, chronic inflammation and disturbed immune functionality. The elevation of Tregs and MDSCs in spleens of tumor-bearing mice was positively correlated with tumor burdens. Consumption of either fish oil or selenium had little or no effect on the levels of Tregs and MDSCs. However, consumption of both fish oil and selenium together presented a synergistic effect--the population of Tregs and MDSCs decreased as opposed to increase of anti-tumor immunity when both fish oil and selenium were supplemented simultaneously, whereby losses of body weight and muscle/fat mass were alleviated significantly.

  19. Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma.

    Science.gov (United States)

    Prado, C M M; Bekaii-Saab, T; Doyle, L A; Shrestha, S; Ghosh, S; Baracos, V E; Sawyer, M B

    2012-05-08

    Cancer cachexia is characterised by skeletal muscle wasting; however, potential for muscle anabolism in patients with advanced cancer is unproven. Quantitative analysis of computed tomography images for loss/gain of muscle in cholangiocarcinoma patients receiving selumetinib (AZD6244; ARRY-142886) in a Phase II study, compared with a separate standard therapy group. Selumetinib is an inhibitor of mitogen-activated protein/extracellular signal-regulated kinase and of interleukin-6 secretion, a putative mediator of muscle wasting. Overall, 84.2% of patients gained muscle after initiating selumetinib; mean overall gain of total lumbar muscle cross-sectional area was 13.6 cm(2)/100 days (∼2.3 kg on a whole-body basis). Cholangiocarcinoma patients who began standard treatment were markedly catabolic, with overall muscle loss of -7.3 cm(2)/100 days (∼1.2 kg) and by contrast only 16.7% of these patients gained muscle. Our findings suggest that selumetinib promotes muscle gain in patients with cholangiocarcinoma. Specific mechanisms and relevance for cachexia therapy remain to be investigated.

  20. Do patients with advanced cancer have any potential for protein anabolism in response to amino acid therapy?

    Science.gov (United States)

    Chevalier, Stéphanie; Winter, Aaron

    2014-05-01

    There is evidence that protein anabolism is achievable before cancer evolves into refractory cachexia with attenuation of muscle loss and even muscle gain. This review summarizes recent observations on the role of total and specific amino acids in promoting protein anabolism in human cancer and revisits prior studies in this context. Analysis of muscle changes in advanced cancer patients indicated opportunities for inducing anabolism. Maintenance and gain in muscle was reported in a majority of patients, from initiation of oncologic treatment and before the final refractory stage. In addition to being substrates, some amino acids, for example leucine, act as intracellular signals to promote protein synthesis. Recent acute studies demonstrated that provision of amino acids, sufficient to considerably elevate circulating leucine concentrations concurrent with other amino acid and nutrient availability, resulted in significant protein anabolism in cancer patients. This occurred even during weight loss and inflammation. Patients with cancer have an anabolic potential to be exploited early on in cachexia development. High-leucine and protein supplements are worth testing as part of a multimodal anabolic approach in long-term trials to confirm their efficacy to sustain anabolism, and attenuate or even reverse muscle wasting.

  1. Pharmacological and pharmacokinetic characterization of 2-piperazine-alpha-isopropyl benzylamine derivatives as melanocortin-4 receptor antagonists.

    Science.gov (United States)

    Chen, Chen; Tucci, Fabio C; Jiang, Wanlong; Tran, Joe A; Fleck, Beth A; Hoare, Sam R; Wen, Jenny; Chen, Takung; Johns, Michael; Markison, Stacy; Foster, Alan C; Marinkovic, Dragan; Chen, Caroline W; Arellano, Melissa; Harman, John; Saunders, John; Bozigian, Haig; Marks, Daniel

    2008-05-15

    A series of 2-piperazine-alpha-isopropylbenzylamine derivatives were synthesized and characterized as melanocortin-4 receptor (MC4R) antagonists. Attaching an amino acid to benzylamines 7 significantly increased their binding affinity, and the resulting compounds 8-12 bound selectively to MC4R over other melanocortin receptor subtypes and behaved as functional antagonists. These compounds were also studied for their permeability using Caco-2 cell monolayers and metabolic stability in human liver microsomes. Most compounds exhibited low permeability and high efflux ratio possibly due to their high molecular weights. They also showed moderate metabolic stability which might be associated with their moderate to high lipophilicity. Pharmacokinetic properties of these MC4R antagonists, including brain penetration, were studied in mice after oral and intravenous administrations. Two compounds identified to possess high binding affinity and selectivity, 10d and 11d, were studied in a murine cachexia model. After intraperitoneal (ip) administration of 1mg/kg dose, mice treated with 10d had significantly more food intake and weight gain than the control animals, demonstrating efficacy by blocking the MC4 receptor. Similar in vivo effects were also observed when 11d was dosed orally at 20mg/kg. These results provide further evidence that a potent and selective MC4R antagonist has potential in the treatment of cancer cachexia.

  2. Zinc-α2-glycoprotein: an adipokine modulator of body fat mass?

    Science.gov (United States)

    Bing, C; Mracek, T; Gao, D; Trayhurn, P

    2010-11-01

    The importance of white adipose tissue in the control of energy balance is now firmly recognized. In addition to fuel storage, adipocytes secrete an array of proteins factors (adipokines), which regulate multiple physiological and metabolic processes as well as influence body fat accumulation. Zinc-α2-glycoprotein (ZAG), a lipid mobilizing factor initially characterized as a tumor product associated with cachexia, has recently been identified as a novel adipokine. Although the exact role of ZAG in adipose tissue remains to be clarified, there is evidence that ZAG expression appears to be inversely related to adiposity, being upregulated in cachexia whereas reduced in obesity. Investigations on the regulation of ZAG give insights into its potential function in adipose tissue with a link to lipid mobilization and an anti-inflammatory action. Recent work shows that ZAG stimulates adiponectin secretion by human adipocytes. Data from genetic studies suggest that ZAG may be a candidate gene for body weight regulation; this is supported by the demonstration that ZAG-knockout mice are susceptible to weight gain, whereas transgenic mice overexpressing ZAG exhibit weight loss. The present review summarizes these new perspectives of ZAG and the potential mechanisms by which it might modulate adipose tissue mass and function.

  3. Effect of zinc-alpha2-glycoprotein (ZAG) on expression of uncoupling proteins in skeletal muscle and adipose tissue.

    Science.gov (United States)

    Sanders, Paul M; Tisdale, Michael J

    2004-08-20

    The plasma protein zinc-alpha2-glycoprotein (ZAG) has been shown to be identical with a lipid mobilizing factor capable of inducing loss of adipose tissue in cancer cachexia through an increased lipid mobilization and utilization. The ability of ZAG to induce uncoupling protein (UCP) expression has been determined using in vitro models of adipose tissue and skeletal muscle. ZAG induced a concentration-dependent increase in the expression of UCP-1 in primary cultures of brown, but not white, adipose tissue, and this effect was attenuated by the beta3-adrenergic receptor (beta3-AR) antagonist SR59230A. A 6.5-fold increase in UCP-1 expression was found in brown adipose tissue after incubation with 0.58 microM ZAG. ZAG also increased UCP-2 expression 3.5-fold in C2C12 murine myotubes, and this effect was also attenuated by SR59230A and potentiated by isobutylmethylxanthine, suggesting a cyclic AMP-mediated process through interaction with a beta3-AR. ZAG also produced a dose-dependent increase in UCP-3 in murine myotubes with a 2.5-fold increase at 0.58 microM ZAG. This effect was not mediated through the beta3-AR, but instead appeared to require mitogen activated protein kinase. These results confirm the ability of ZAG to directly influence UCP expression, which may play an important role in lipid utilization during cancer cachexia.

  4. Therapeutic Potential of Targeting the Ghrelin Pathway.

    Science.gov (United States)

    Colldén, Gustav; Tschöp, Matthias H; Müller, Timo D

    2017-04-11

    Ghrelin was discovered in 1999 as the endogenous ligand of the growth-hormone secretagogue receptor 1a (GHSR1a). Since then, ghrelin has been found to exert a plethora of physiological effects that go far beyond its initial characterization as a growth hormone (GH) secretagogue. Among the numerous well-established effects of ghrelin are the stimulation of appetite and lipid accumulation, the modulation of immunity and inflammation, the stimulation of gastric motility, the improvement of cardiac performance, the modulation of stress, anxiety, taste sensation and reward-seeking behavior, as well as the regulation of glucose metabolism and thermogenesis. Due to a variety of beneficial effects on systems' metabolism, pharmacological targeting of the endogenous ghrelin system is widely considered a valuable approach to treat metabolic complications, such as chronic inflammation, gastroparesis or cancer-associated anorexia and cachexia. The aim of this review is to discuss and highlight the broad pharmacological potential of ghrelin pathway modulation for the treatment of anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, renal and pulmonary disease, gastrointestinal (GI) disorders, inflammatory disorders and metabolic syndrome.

  5. MRI findings of serous atrophy of bone marrow and associated complications

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    Boutin, Robert D. [Department of Radiology, Sacramento, CA (United States); White, Lawrence M. [University of Toronto, Joint Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada); Laor, Tal [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Spitz, Damon J. [New England Baptist Hospital, Department of Radiology, Boston, MA (United States); Lopez-Ben, Robert R. [Carolinas HealthCare System, Charlotte Radiology, Diagnostic Radiology, Charlotte, NC (United States); Stevens, Kathryn J. [Stanford University, Department of Radiology, Stanford, CA (United States); Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States)

    2015-09-15

    To report the MRI appearance of serous atrophy of bone marrow (SABM) and analyse clinical findings and complications of SABM. A retrospective search of MRI examinations of SABM was performed. Symptoms, underlying conditions, MRI findings, delay in diagnosis and associated complications were recorded. We identified 30 patients (15 male, 15 female; mean age: 46 ± 21 years) with MRI findings of SABM. Underlying conditions included anorexia nervosa (n = 10), cachexia from malignant (n = 5) and non-malignant (n = 7) causes, massive weight loss after bariatric surgery (n = 1), biliary atresia (n = 1), AIDS (n = 3), endocrine disorders (n = 2) and scurvy (n = 1). MRI showed mildly hypointense signal on T1- weighted and hyperintense signal on fat-suppressed fluid-sensitive images of affected bone marrow in all cases and similar signal abnormalities of the adjacent subcutaneous fat in 29/30 cases. Seven patients underwent repeat MRI due to initial misinterpretation of bone marrow signal as technical error. Superimposed fractures of the hips and lower extremities were common (n = 14). SABM occurs most commonly in anorexia nervosa and cachexia. MRI findings of SABM are often misinterpreted as technical error requiring unnecessary repeat imaging. SABM is frequently associated with fractures of the lower extremities. (orig.)

  6. Fiber type-specific nitric oxide protects oxidative myofibers against cachectic stimuli.

    Directory of Open Access Journals (Sweden)

    Zengli Yu

    2008-05-01

    Full Text Available Oxidative skeletal muscles are more resistant than glycolytic muscles to cachexia caused by chronic heart failure and other chronic diseases. The molecular mechanism for the protection associated with oxidative phenotype remains elusive. We hypothesized that differences in reactive oxygen species (ROS and nitric oxide (NO determine the fiber type susceptibility. Here, we show that intraperitoneal injection of endotoxin (lipopolysaccharide, LPS in mice resulted in higher level of ROS and greater expression of muscle-specific E3 ubiqitin ligases, muscle atrophy F-box (MAFbx/atrogin-1 and muscle RING finger-1 (MuRF1, in glycolytic white vastus lateralis muscle than in oxidative soleus muscle. By contrast, NO production, inducible NO synthase (iNos and antioxidant gene expression were greatly enhanced in oxidative, but not in glycolytic muscles, suggesting that NO mediates protection against muscle wasting. NO donors enhanced iNos and antioxidant gene expression and blocked cytokine/endotoxin-induced MAFbx/atrogin-1 expression in cultured myoblasts and in skeletal muscle in vivo. Our studies reveal a novel protective mechanism in oxidative myofibers mediated by enhanced iNos and antioxidant gene expression and suggest a significant value of enhanced NO signaling as a new therapeutic strategy for cachexia.

  7. Association between an inflammatory-nutritional index and nutritional status in cancer patients.

    Science.gov (United States)

    Alberici Pastore, Carla; Paiva Orlandi, Silvana; González, María Cristina

    2013-01-01

    Cachexia is a multifatorial syndrome characterized by loss of body weight, fat and muscle, increasing morbidity and mortality. The use of an index accounting for both serum albumin and C Reactive Protein levels could make early identification of cachexia easier. To evaluate the variation of an inflammatory nutritional index related to nutritional status in cancer patients. Cross sectional study including patients with gastrointestinal and lung cancer of a public chemotherapy service in Brazil. Serum albumin and C Reactive Protein were measured and the nutritional status was defined by Subjective Global Assessment. Statistical analyses were performed using Stata 9.2(TM). A total of 74 patients were evaluated, 58.1% of them were male, mean age 63.4 ± 11.9 years old. Gastrointestinal cancer was the most prevalent type (71.6%). Only 13.7% of the patients were well nourished and 21.9% were severely malnourished. C Reactive Protein significantly increased according to nutritional status decline (p=0.03). When the albumin from patients with systemic inflammation was evaluated, there was no significant variation in relation to nutritional status (p=0.06). The Inflammatory Nutritional Index significantly varied in relation to nutritional status independent of the systemic inflammation (p=0.02). Inflammatory Nutritional Index can be an adjuvant way for biochemical nutritional assessment and follow up in cancer patients with systemic inflammation. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  8. Nutritional status and nutritional support before and after pancreatectomy for pancreatic cancer and chronic pancreatitis.

    Science.gov (United States)

    Karagianni, Vasiliki Th; Papalois, Apostolos E; Triantafillidis, John K

    2012-12-01

    Cachexia, malnutrition, significant weight loss, and reduction in food intake due to anorexia represent the most important pathophysiological consequences of pancreatic cancer. Pathophysiological consequences result also from pancreatectomy, the type and severity of which differ significantly and depend on the type of the operation performed. Nutritional intervention, either parenteral or enteral, needs to be seen as a method of support in pancreatic cancer patients aiming at the maintenance of the nutritional and functional status and the prevention or attenuation of cachexia. Oral nutrition could reduce complications while restoring quality of life. Enteral nutrition in the post-operative period could also reduce infective complications. The evidence for immune-enhanced feed in patients undergoing pancreaticoduodenectomy for pancreatic cancer is supported by the available clinical data. Nutritional support during the post-operative period on a cyclical basis is preferred because it is associated with low incidence of gastric stasis. Postoperative total parenteral nutrition is indicated only to those patients who are unable to be fed orally or enterally. Thus nutritional deficiency is a relatively widesoread and constant finding suggesting that we must optimise the nutritional status both before and after surgery.

  9. [Effect of invigorating spleen and detoxification decoction on MHC I/MHC II in spleen-deficiency liver cancer rats survival].

    Science.gov (United States)

    Li, Yu-Long; Sun, Bao-Guo; Xiang, Ting; Chen, Ze-Xiong; Zhang, Shi-Jun

    2014-03-01

    To explore that Invigorating Spleen and Detoxification Decoction (ISD) enhanced the survival of spleen-deficiency liver cancer rats and the effect on major histocompatibility complex I (MHC I) and major histocompatibility complex II (MHC II). 105 male Wistar rats were randomly divided into blank control group, liver cancer model group, spleen-deficiency model group, spleen-deficiency liver cancer model group, Thymopentin group and spleen-deficiency liver cancer model groups treated by low and high-concentration ISD for modeling and intervention. Recorded the animals' weight, survival time, moribund state and cachexia score of liver cancer rats, and collected specimens in the experiment. Immunohistochemistry and Western blot were used to detect MHC I/MHC II expression in liver tissue and liver cancer tissue. The cumulative survival of high concentration ISD group and Thymopentin group were higher than that of the other groups (P liver cancer model groups, MHC I expression in liver tissue was higher than that in liver cancer tissue, both in these two tissues, expression of high-concentration ISD group was the strongest (P liver cancer tissue was stronger than that in liver tissue, expression of high-concentration ISD group was the strongest in liver tissue, but in liver cancer tissue, the spleen-deficiency liver cancer model group was the strongest (P < 0.01). ISD can significantly decrease the progression of cachexia caused by transplantable tumor and prolong the survival time, the effect may be related to increasing MHC I/MHC II expression.

  10. Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice.

    Science.gov (United States)

    Fermoselle, Clara; García-Arumí, Elena; Puig-Vilanova, Ester; Andreu, Antoni L; Urtreger, Alejandro J; de Kier Joffé, Elisa D Bal; Tejedor, Alberto; Puente-Maestu, Luís; Barreiro, Esther

    2013-09-01

    What is the central question of this study? We explored whether experimental cancer-induced cachexia may alter mitochondrial respiratory chain (MRC) complexes and oxygen uptake in respiratory and peripheral muscles,and whether signalling pathways, proteasome and oxidative stress influence that process. What is the main finding and what is its importance? In cancer cachectic mice, MRC complexes and oxygen consumption were decreased in the diaphragm and gastrocnemius. Blockade of nuclear factor-κB and mitogen-activated protein kinase actions partly restored the muscle mass and force and corrected the MRC dysfunction,while concomitantly reducing tumour burden. Antioxidants improved mitochondrial oxygen consumption without eliciting effects on the loss of muscle mass and force or the tumour size,whereas bortezomib reduced tumour burden without influencing muscle mass and strength or MRC function. Abnormalities in mitochondrial content, morphology and function have been reported in several muscle-wasting conditions. We specifically explored whether experimental cancer-induced cachexia may alter mitochondrial respiratory chain (MRC) complexes and oxygen uptake in respiratory and peripheral muscles, and whether signalling pathways, proteasomes and oxidative stress may influence that process. We evaluated complex I, II and IV enzyme activities (specific activity assays) and MRC oxygen consumption (polarographic measurements) in diaphragm and gastrocnemius of cachectic mice bearing the LP07 lung tumour, with and without treatment with N-acetylcysteine, bortezomib and nuclear factor-κB (sulfasalazine) and mitogen-activated protein kinases (MAPK, U0126) inhibitors (n = 10 per group for all groups). Whole-body and muscle weights and limb muscle force were also assessed in all rodents at baseline and after 1 month. Compared with control animals, cancer cachectic mice showed a significant reduction in body weight gain, smaller sizes of the diaphragm and gastrocnemius, lower

  11. L-leucine dietary supplementation modulates muscle protein degradation and increases pro-inflammatory cytokines in tumour-bearing rats.

    Science.gov (United States)

    Cruz, Bread; Oliveira, André; Gomes-Marcondes, Maria Cristina Cintra

    2017-08-01

    Cancer cachexia is characterised by involuntary weight loss associated with systemic inflammation and metabolic changes. Studies aimed at maintaining lean body mass in cachectic tumour-bearing hosts have made important contributions reducing the number of deaths and improving the quality of life. In recent years, leucine has demonstrated effective action in maintaining lean body mass by decreasing muscle protein degradation. Currently, there is a growing need to understand how leucine stimulates protein synthesis and acts protectively in a cachectic organism. Thus, this study aimed to assess the effects of a leucine-rich diet on protein degradation signalling in muscle over the course of tumour growth. Animals were distributed into four experimental groups, which did or did not receive 2×10 6 viable Walker-tumour cells. Some were fed a leucine-rich diet, and the groups were subsequently sacrificed at three different time points of tumour evolution (7th, 14th, and 21st days). Protein degradation signals, as indicated by ubiquitin-proteasome subunits (11S, 19S, and 20S) and pro- and anti-inflammatory cytokines, were analysed in all experimental groups. In tumour-bearing animals without nutritional supplementation (W7, W14, and W21 groups), we observed that the tumour growth promoted a concurrent decrease in muscle protein, a sharp increase in pro-inflammatory cytokines (TNFα, IL-6, and IFNγ), and a progressive increase in proteasome subunits (19S and 20S). Thus, the leucine-supplemented tumour-bearing groups showed improvements in muscle mass and protein content, and in this specific situation, the leucine-rich diet led to an increase on the day in cytokine profile and proteasome subunits mainly on the 14th day, which subsequently had a modulating effect on tumour growth on the 21st day. These results indicate that the presence of leucine in the diet may modulate important aspects of the proteasomal pathway in cancer cachexia and may prevent muscle wasting due to

  12. The effect of disease activity on body composition and resting energy expenditure in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Binymin K

    2011-05-01

    Full Text Available K Binymin1,3, AL Herrick1, GL Carlson2, SJ Hopkins21University of Manchester, Rheumatic Diseases Centre, 2Infection Injury and Inflammation Group, and Brain Injury Research Group, Manchester Academic Health Science Centre and University of Manchester Faculty of Medical and Human Sciences, Salford Royal Hospitals NHS Trust, Salford, UK; 3Southport District General Hospital, Southport, UKIntroduction: Cachexia is associated with rheumatoid arthritis (RA, but whether it is attributable primarily to reduced dietary intake or increased metabolism is unclear, as is the association with inflammation. To examine whether rheumatoid cachexia is related to increased energy expenditure, reduced food intake, or an inflammatory cytokine response we undertook a prospective, longitudinal study of patients with RA, during periods of relative relapse and remission of inflammation.Methods: Sixteen patients admitted to hospital with a flare of RA were assessed clinically to determine disease activity and were re-examined 6 weeks later. Their fat-free mass (FFM, dietary intake, resting energy expenditure (REE, and plasma concentrations of interleukin-6 (IL-6 were also measured. Data were compared with those from 16 healthy, age- and sex-matched controls.Results: At baseline the body weight, body mass index, and FFM of patients with RA were significantly lower than those of controls. Disease activity scores of patients (6.39 ± 0.8 were reduced when the patients were re-examined 6 weeks later (5.23 ± 1.26 and FFM was no longer statistically different from that of controls (visit 1 = 25.8 ± 10.1 and visit 2 = 26.8 ± 9.5 versus controls = 32.3 ± 10.9. There were no differences in food intake between patients and controls or between patients studied at the 2 time points, but REE was greater in patients after correcting for FMM (visit 1 = 62.2 ± 24.7, visit 2 = 59.7 ± 26.3 versus controls = 46.0 ± 13.7. Plasma IL-6 concentrations were significantly higher in

  13. Low skeletal muscle radiation attenuation and visceral adiposity are associated with overall survival and surgical site infections in patients with pancreatic cancer.

    Science.gov (United States)

    van Dijk, David P J; Bakens, Maikel J A M; Coolsen, Mariëlle M E; Rensen, Sander S; van Dam, Ronald M; Bours, Martijn J L; Weijenberg, Matty P; Dejong, Cornelis H C; Olde Damink, Steven W M

    2017-04-01

    Cancer cachexia and skeletal muscle wasting are related to poor survival. In this study, quantitative body composition measurements using computed tomography (CT) were investigated in relation to survival, post-operative complications, and surgical site infections in surgical patients with cancer of the head of the pancreas. A prospective cohort of 199 patients with cancer of the head of the pancreas was analysed by CT imaging at the L3 level to determine (i) muscle radiation attenuation (average Hounsfield units of total L3 skeletal muscle); (ii) visceral adipose tissue area; (iii) subcutaneous adipose tissue area; (iv) intermuscular adipose tissue area; and (v) skeletal muscle area. Sex-specific cut-offs were determined at the lower tertile for muscle radiation attenuation and skeletal muscle area and the higher tertile for adipose tissues. These variables of body composition were related to overall survival, severe post-operative complications (Dindo-Clavien ≥ 3), and surgical site infections (wounds inspected daily by an independent trial nurse) using Cox-regression analysis and multivariable logistic regression analysis, respectively. Low muscle radiation attenuation was associated with shorter survival in comparison with moderate and high muscle radiation attenuation [median survival 10.8 (95% CI: 8.8-12.8) vs. 17.4 (95% CI: 14.7-20.1), and 18.5 (95% CI: 9.2-27.8) months, respectively; P attenuation combined with either low visceral adipose tissue or age attenuation was inversely correlated with intermuscular adipose tissue (rp  = -0.697, P attenuation was associated with reduced survival, and high visceral adiposity was associated with an increase in surgical site infections. The strong correlation between muscle radiation attenuation and intermuscular adipose tissue suggests the presence of ectopic fat in muscle, warranting further investigation. CT image analysis could be implemented in pre-operative risk assessment to assist in treatment

  14. TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator.

    Directory of Open Access Journals (Sweden)

    Vicky Wang-Wei Tsai

    Full Text Available The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1(-/- weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1(-/- mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1(-/- mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage.

  15. N-methyl D-aspartate receptor synaptonuclear signaling and neuronal migration factor (Nsmf) plays a novel role in myoblast proliferation.

    Science.gov (United States)

    Moon, Hyo Youl

    2015-01-01

    Myogenesis, the formation and regeneration of muscular tissue, is a fundamental factor in embryonic development. N-methyl D-aspartate (NMDA) receptor synaptonuclear signaling and neuronal migration factor (Nsmf) mediates NMDA receptor endocytosis in GnRH neuronal cells. NMDA receptor is involved in myoblast differentiation by regulating Ca2 (+) dependent fusion of myocytes. In this study, we investigated the role of Nsmf in myoblast proliferation and differentiation. Quantitative-PCR, immunoblotting, and immunohistochemistry results showed that the Nsmf expression levels increased during both the differentiation and proliferation of myocytes. Knockdown of Nsmf in myocytes by siRNA did not affect the myocyte differentiation marker myogenin. However, flow cytometry showed that the proliferation rate of the Nsmf-knockdown cells was reduced compared to the control cells. Therefore, our results indicate that Nsmf is a novel myogenic factor that can enhance myoblast proliferation. Furthermore, Nsmf may be an important therapeutic target in diseases associated with aging, muscular dystrophy, or cachexia.

  16. The relationship between body weight and inflammation: Lesson from anti-TNF-α antibody therapy.

    Science.gov (United States)

    Peluso, Ilaria; Palmery, Maura

    2016-01-01

    Obesity is associated with many pathological conditions. Tumor Necrosis Factor-α (TNF-α) is one of the key mediators of inflammation involved in the obesity-related insulin resistance development. We aim to review the human evidence useful to clarify the relationship between inflammation and body weight, with particular reference to TNF-α. Genetic polymorphisms and epigenetic factors, such as diet, could affect TNF-α activity. TNF-α is associated with obesity, but also with anorexia and cachexia. Despite the role of TNF-α in obesity-related diseases, anti-TNF-α antibody therapy is associated with an increase in adiposity. In conclusion the reviewed results suggest that inflammation is more likely a consequence rather than a cause of obesity. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  17. [Establishment of animal model with B lineage acute leukemia in nude mice for evaluation of new therapeutic agents].

    Science.gov (United States)

    Li, Li-xia; Tang, Yong-min; Gu, Wei-zhong; Tang, Hong-feng; Qian, Bai-qin; Shen, Hong-qiang; Luo, Chun-fang

    2008-09-01

    To establish an acute leukemia animal model for testing new therapeutic agents in vivo. Nude mice were intraperitoneally injected with 2 mg cyclophosphamide, 24 h later 5 x 10(6) acute B-cell leukemia Nalm-6 cells was inoculated via the tail vein, then monitored daily. When animals were paralyzed or dying, the organs including the liver, spleen, lung, heart, kidney, brain, bone marrow, pancreas, testes were removed and fixed with formalin, examined by routine histopathology. After Nalm-6 cells were inoculated the mean survival of mice were( 19.4+/-0.55)d (n=6). The paralysis of mice was followed by weight loss, bent spines, hogback, cachexia and death. Histopathological examination showed that the tumor cells infiltrated liver, spleen, kidney, lung, meninges, interior cerebrum, the liver and kidney were the most affected organs. B lineage acute leukemia animal model has been successfully established in the nude mice, which is suitable for testing new therapeutic agents.

  18. Impact of physiotherapy on patients with advanced lung cancer.

    Science.gov (United States)

    Ozalevli, Sevgi

    2013-01-01

    Patients with lung cancer have high mortality and high morbidity. Lung cancer-related symptoms and problems such as dyspnea, fatigue, pain, and cachexia that begin in the early phase later result in poor physical functioning, psychosocial, and quality of life status. In addition, advancing age is associated with significant comorbidity. These patients may benefit from multidisciplinary therapy to reduce the perceived severity of dyspnea and fatigue and increase physical functioning and quality of life. Based on management of symptoms and problems such as dyspnea, physical inactivity, cancer-related fatigue, respiratory secretions, pain, and anxiety-depression of these patients, it is thought that physiotherapy techniques can be used on advanced lung cancer patients following a comprehensive evaluation. However, well-designed, prospective, and randomized-controlled trials are needed to prove the efficacy of physiotherapy and pulmonary rehabilitation in general for patients with advanced lung cancer.

  19. Medical image of the week: central pontine myelinolysis

    Directory of Open Access Journals (Sweden)

    Siddiqi TA

    2014-01-01

    Full Text Available A 38-year-old woman with history of alcohol abuse was admitted with generalized weakness, dehydration, alcoholic hepatitis, hyponatremia (serum sodium 116 mM/L, and cachexia (BMI 19 kg/m2. She developed hypoxemic respiratory failure after intravenous fluid resuscitation and required intubation and mechanical ventilation. Neurological exam revealed motor weakness, hyporeflexia, ataxia, and unsustained clonus. Neurology consultation was obtained and MRI revealed hyperintensity in the pons consistent with osmotic demyelination syndrome (1. Review of her records revealed her sodium level increased by 8 mM/L in first 6 hours of presentation, and then a slow increase of 4-6 mM/L daily to the normal range. She received nutritional support and aggressive physical therapy, and was discharged to skilled nursing facility after six weeks of hospitalization.

  20. Benefits of Exercise in Rheumatoid Arthritis

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    Jennifer K. Cooney

    2011-01-01

    Full Text Available This paper aims to highlight the importance of exercise in patients with rheumatoid arthritis (RA and to demonstrate the multitude of beneficial effects that properly designed exercise training has in this population. RA is a chronic, systemic, autoimmune disease characterised by decrements to joint health including joint pain and inflammation, fatigue, increased incidence and progression of cardiovascular disease, and accelerated loss of muscle mass, that is, “rheumatoid cachexia”. These factors contribute to functional limitation, disability, comorbidities, and reduced quality of life. Exercise training for RA patients has been shown to be efficacious in reversing cachexia and substantially improving function without exacerbating disease activity and is likely to reduce cardiovascular risk. Thus, all RA patients should be encouraged to include aerobic and resistance exercise training as part of routine care. Understanding the perceptions of RA patients and health professionals to exercise is key to patients initiating and adhering to effective exercise training.

  1. [Effects of carnitine and cobamamide on the dynamics of mental work capacity in patients with anorexia nervosa].

    Science.gov (United States)

    Korkina, M V; Korchak, G M; Kareva, M A

    1992-01-01

    The authors relate the results of studying intellectual work fitness in patients with anorexia nervosa (in the stage of cachexia) receiving the vitamin-like drugs carnitine and cobamamide. It has been shown that the long-term food deprivation leads to a reduction of intellectual work fitness, lability of productivity, fluctuations in the work quality, appearance of latent fatigue. In spite of the fact that standard nonspecific treatment ameliorates intellectual work fitness, it does not lead to its normalization. The use of carnitine and cobamamide in the course of nonspecific treatment results in the reduction of the time spent on task implementation, a rise of the work rate as compared to the control group. However, this does not fully remove latent fatigue and does not bring about complete recovery to normal of intellectual work fitness. The combined use of carnitine and cobamamide eliminates fluctuations in the work rate and normalizes the scope and productivity of intellectual work.

  2. Strategies for potential manipulation of anorexia during acute and chronic disease.

    Science.gov (United States)

    Plata-Salamán, C R

    1995-01-01

    Acute and chronic pathologic processes and immunotherapy in humans are frequently accompanied by anorexia and other neurologic manifestations of disease. Various signals (including cytokines such as immunomodulators) are responsible for anorexia during disease or immunotherapy. Anorexia during disease can be beneficial or deleterious to an organism depending on the timing and duration. For example, a restriction in the intake of micronutrients and macronutrients may be part of the biological roles of the temporal anorexia that accompanies infection. However, diseases with long-term anorexia may be associated with cachexia. Present research on anorexia focuses on elucidating the immunochemical and neuronal mechanisms that contribute to anorexia and on developing potential interventions including the following: 1) nutritional substrates; 2) monoclonal antibodies, receptor antagonists, soluble receptors, and other cytokine (including endogenous) inhibitors; 3) glucocorticoids and other steroids; 4) nonsteroidal antiinflammatory agents; 5) neuropeptide inhibitors of cytokine action; and 6) antisense strategies.

  3. Body composition as measured by in vivo neutron activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cohn, S.H.; Sawitsky, A.; Vartsky, D.; Yasumura, S.; Zanzi, I.; Gartenhaus, W.; Ellis, K.J.

    1979-01-01

    A large scale study is currently underway on the changes in body composition resulting from the cachexia of malignancy. The ultimate objective of the overall project is to assess the changes in body composition associated with hyperalimentation and other modes of nutritional support to cancer patients. The first phase of this study is now in progress. In this phase, a study is being made of a control group of normal patients to provide baseline data against which data from cancer patients can be evaluated. Total body nitrogen and potassium are measured in a group of normal men and women, and are analyzed as a function of age. Additionally, changes in skeletal mass (total body calcium) are also recorded, and body water is measured simultaneously with the use of tritiated water.

  4. A Novel Non-Peptidic Agonist of the Ghrelin Receptor with Orexigenic Activity In vivo

    Science.gov (United States)

    Pastor-Cavada, Elena; Pardo, Leticia M.; Kandil, Dalia; Torres-Fuentes, Cristina; Clarke, Sarah L.; Shaban, Hamdy; McGlacken, Gerard P.; Schellekens, Harriet

    2016-11-01

    Loss of appetite in the medically ill and ageing populations is a major health problem and a significant symptom in cachexia syndromes, which is the loss of muscle and fat mass. Ghrelin is a gut-derived hormone which can stimulate appetite. Herein we describe a novel, simple, non-peptidic, 2-pyridone which acts as a selective agonist for the ghrelin receptor (GHS-R1a). The small 2-pyridone demonstrated clear agonistic activity in both transfected human cells and mouse hypothalamic cells with endogenous GHS-R1a receptor expression. In vivo tests with the hit compound showed significant increased food intake following peripheral administration, which highlights the potent orexigenic effect of this novel GHS-R1a receptor ligand.

  5. [Malnutrition due to an extremely 'healthy' diet; a new eating disorder?].

    Science.gov (United States)

    Nauta, K; Toxopeus, K; Eekhoff, E M W

    2016-01-01

    A 71-year-old male was admitted to our hospital with heart failure, cachexia and biochemical disturbances due to a diet consisting of exclusively vegetables, oil and water. Our investigations showed that this diet was a consequence of an excessive preoccupation with health. The patient did not meet criteria for an eating disorder or other DSM-IV psychiatric disorder. We conclude that malnutrition due to health fad diets may be an underestimated medical problem. There is no specific psychopathological disorder that covers this behaviour, and there is no knowledge of its epidemiology. Popular literature is paying a great deal attention to orthorexia nervosa, an alleged eating disorder that describes a pathological obsession with healthy food. In medical literature this concept has been largely neglected, although eating disorder specialists frequently observe this behaviour in their practice. More clinical and scientific attention for this phenomenon is necessary to determine its epidemiology, validity and clinical picture.

  6. Characterization of Mycobacterium salmoniphilum as causal agent of mycobacteriosis in Atlantic salmon, Salmo salar L., from a freshwater recirculation system.

    Science.gov (United States)

    Aro, L; Correa, K; Martínez, A; Ildefonso, R; Yáñez, J M

    2014-04-01

    Thirty Atlantic salmon, Salmo salar L., with low corporal condition relative to other fish present in the culture system, were sampled from a freshwater recirculation pisciculture located in Chile. The most characteristic signs and lesions were cachexia and presence of multiple greyish-white granulomas within internal organs. The external and internal lesions, along with the microscopic, histologic and biochemical findings, were consistent with mycobacteriosis. The identification of Mycobacterium salmoniphilum as the causal agent of the lesions was possible through the use of molecular analyses. This study represents the first report of Mycobacterium salmoniphilum in a freshwater recirculation system and the first case of fish mycobacteriosis described in Chile. © 2013 John Wiley & Sons Ltd.

  7. The efficacy of the product Albendazole 10% of gastrointestinal nematode parasitism in sheep tested

    Directory of Open Access Journals (Sweden)

    Florin Stefan Hora

    2014-12-01

    Full Text Available Trichostrongylids are helminths of ruminants, located gastro intestinally. The disease generated by them is clinically manifested mainly by: diarrhea, weight loss, anemia and cachexia. They are produced by parasites belonging to the family Trichostrongylidae with genres: Ostertagia, Haemonchus, Trichostrongylus, Cooperia and Nematodirus. The study was accomplished in 2013 in Hidiseul de Sus village, Bihor County, and aimed to test the effectiveness of the Albendazole 10% in the natural infestations with gastrointestinal nematodes in sheep. Sheep studied consisted of 60 individuals from Turcana breed. Feces were examined by flotation method and to know the infestation level McMaster method was used, calculating the EPG value on day 0 of treatment, day 7 and day 14 post treatments. Anthelmintic efficacy (E% of the used product was of 97.03% after the FECRT formula. For a more meaningful expression it was used also Presidente and Borgsteede relations, where the result of efficiency for the tested product was 98% for both formulas.

  8. Paraneoplastic endocrine-metabolic syndromes

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    Marco Grandi

    2013-04-01

    Full Text Available BACKGROUND The paraneoplastic syndromes (PS are characterized by the presence of biochemical alterations, signs and symptoms expressive of cancer distance action into the patient’s organism. Sometimes these syndromes can precede the evidence of malignancy even of some years or can correspond to cancer relapse. PS, even being characterized by general symptoms (fever, anorexia, cachexia, may occur with neurological, rheumathological, osteoarticular, vascular, haematological, nephrological and endocrinological/metabolic symptoms; the latter ones are discussed in this article. AIM OF THE STUDY Here we will focus on the most common PS: paraneoplastic hypercalcemia, inappropriate secretion of antidiuretic hormone (SIADH and paraneoplastic Cushing syndrome. CONCLUSIONS Our work can be useful in the diagnosis and therapeutic management of paraneoplastic syndromes.

  9. For whom the bell tolls? DING proteins in health and disease.

    Science.gov (United States)

    Berna, Anne; Bernier, François; Chabrière, Eric; Elias, Mikael; Scott, Ken; Suh, Andrew

    2009-07-01

    DING proteins, identified mainly by their eponymous N-terminal sequences, are ubiquitous in living organisms. Amongst bacteria, they are common in pseudomonads, and have been characterised with respect to genetics and structure. They form part of a wider family of phosphate-binding proteins, with emerging roles in phosphate acquisition and pathogenicity. Many DING proteins have been isolated in eukaryotes, in which they have been associated with very diverse biological activities, often in the context of possible signalling roles. Disease states in which DING proteins have been implicated include rheumatoid arthritis, lithiasis, atherosclerosis, some tumours and tumour-associated cachexia, and bacterial and viral adherence. Complete genetic and structural characterisation of eukaryotic DING genes and proteins is still lacking, though the phosphate-binding site seems to be conserved. Whether as bacterial proteins related to bacterial pathogenicity, or as eukaryotic components of biochemical signalling systems, DING proteins require further study.

  10. Reasons for hospitalization in HIV-infected children in West Africa

    DEFF Research Database (Denmark)

    Dicko, Fatoumata; Desmonde, Sophie; Koumakpai, Sikiratou

    2014-01-01

    -infected children in West Africa (IeDEA West Africa collaboration). METHODS: We performed a six-month prospective multicentre survey from April to October 2010 in five HIV-specialized paediatric hospital wards in Ouagadougou, Accra, Cotonou, Dakar and Bamako. Baseline and follow-up data during hospitalization were......%) died during hospitalization and four (3%) were transferred out. The leading causes of hospitalization were WHO stage 3 opportunistic infections (37%), non-AIDS-defining events (28%), cachexia and other WHO stage 4 events (25%). CONCLUSIONS: Overall, most causes of hospitalizations were HIV related...... but one hospitalization in three was caused by a non-AIDS-defining event, mostly in children on ART. HIV-related fatality is also high despite the scaling-up of access to ART in resource-limited settings....

  11. Profile of nursing diagnoses of hospitalized patients in an infectious disease unit

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    Vinicius Lino de Souza Neto

    Full Text Available Objective: To define the profile of nursing diagnoses of hospitalized patients at an infectious diseases unit.Methods: This is a descriptive study based on the quantitative approach conducted at an infectious diseases unit in Paraiba, Brazil, from January to February 2014. The data collection instrument was based on the Theory of Basic Human Needs by Wanda de Aguiar Horta, followed by the classification system CIPE(r version 2.0 to construct the diagnoses.Results: Data analysis resulted in 36 nursing diagnoses statements, with a higher prevalence of impaired food intake, cachexia, impaired spontaneous bladder elimination, impaired oral cavity hygiene, exposure to contamination, rapid heart rate, insomnia, drug abuse, alcohol and tobacco abuse, social isolation, acceptance and fear.Conclusions: The identification of a diagnostics profile is critical to guide nursing interventions.

  12. Clinical nutrition guidelines of the French Speaking Society of Clinical Nutrition and Metabolism (SFNEP): Summary of recommendations for adults undergoing non-surgical anticancer treatment.

    Science.gov (United States)

    2014-08-01

    Up to 50% of patients with cancer suffer from weight loss and undernutrition (as called cachexia) even though it is rarely screened or properly handled. Patients' prognosis and quality of life could be greatly improved by simple and inexpensive means encompassing nutritional status assessment and effective nutritional care. These guidelines aim to give health professionals and patients practical and up-to-date advice to manage nutrition in the principal situations encountered during the cancer course according to the type of tumour and treatment (i.e. radio and/or chemotherapy). Specific suggestions are made for palliative and elderly patients because of specific risks of undernutrition and related comorbidities in this subset. Levels of evidence and grades of recommendations are detailed as stated by current literature and consensus opinion of clinical experts in each field. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. An in Vitro and in Vivo Investigation of Bivalent Ligands That Display Preferential Binding and Functional Activity for Different Melanocortin Receptor Homodimers.

    Science.gov (United States)

    Lensing, Cody J; Freeman, Katie T; Schnell, Sathya M; Adank, Danielle N; Speth, Robert C; Haskell-Luevano, Carrie

    2016-04-14

    Pharmacological probes for the melanocortin receptors have been utilized for studying various disease states including cancer, sexual function disorders, Alzheimer's disease, social disorders, cachexia, and obesity. This study focused on the design and synthesis of bivalent ligands to target melanocortin receptor homodimers. Lead ligands increased binding affinity by 14- to 25-fold and increased cAMP signaling potency by 3- to 5-fold compared to their monovalent counterparts. Unexpectedly, different bivalent ligands showed preferences for particular melanocortin receptor subtypes depending on the linker that connected the binding scaffolds, suggesting structural differences between the various dimer subtypes. Homobivalent compound 12 possessed a functional profile that was unique from its monovalent counterpart providing evidence of the discrete effects of bivalent ligands. Lead compound 7 significantly decreased feeding in mice after intracerebroventricular administration. To the best of our knowledge, this is the first report of a melanocortin bivalent ligand's in vivo physiological effects.

  14. The Pentapeptide RM-131 Promotes Food Intake and Adiposity in Wildtype Mice but Not in Mice Lacking the Ghrelin Receptor

    DEFF Research Database (Denmark)

    Fischer, Katrin; Finan, Brian; Clemmensen, Christoffer

    2014-01-01

    The gastrointestinal peptide hormone ghrelin is the endogenous ligand of the growth hormone secretagogue receptor (a.k.a. ghrelin receptor, GHR). Currently, ghrelin is the only circulating peripheral hormone with the ability to promote a positive energy balance by stimulating food intake while...... decreasing energy expenditure and body fat utilization, as defined in rodents. Based on these and additional, beneficial effects on metabolism, the endogenous ghrelin system is considered an attractive target to treat diverse pathological conditions including those associated with eating/wasting disorders...... and cachexia. As the pharmacological potential of ghrelin is hampered by its relatively short half-life, ghrelin analogs with enhanced pharmacokinetics offer the potential to sustainably improve metabolism. One of these ghrelin analogs is the pentapeptide RM-131, which promotes food intake and adiposity...

  15. Experimental oral lead toxicity in young dogs

    Energy Technology Data Exchange (ETDEWEB)

    Stowe, H.D.; Goyer, R.A.; Krigman, M.M.; Wilson, M.; Cates, M.

    1973-02-01

    Litter-mate male pups were fed a calcium-and-phosphorus-low purified diet with and without 100 ppm of lead as lead acetate from age 6 to 18 weeks. Lead-toxic dogs exhibited cyclic but terminally severe anorexia and cachexia, significant anemia, normoblastocytosis and leukopenia within six weeks, hypoproteinemia, decreased serum albumin, ..cap alpha../sub 1/-globulin, ..beta../sub 2/-globulin, alkaline phosphatase and lactic dehydrogenase 1, elevated serum glutamic oxaloacetic and pyruvic transaminases, delayed closure of the thoracic vertebral epiphyses, lead lines in the distal radii and thoracic spinous processes, enlargement of liver, kidney, and brain, hepatic fatty metamorphosis, focal proximal renal tubular necrosis, hydropic degeneration of spermatognia, and lead inclusion body formation. Approximately 97% of the tissue lead was estimated to be skeletal; the greatest concentration of lead in the brain was found in the occipital gray matter.

  16. Atractylodin Induces Myosin Light Chain Phosphorylation and Promotes Gastric Emptying through Ghrelin Receptor

    Directory of Open Access Journals (Sweden)

    Yu Bai

    2017-01-01

    Full Text Available Atractylodin is one of the main constituents in the rhizomes of Atractylodes lancea Thunb., being capable of treating cancer cachexia-anorexia and age-related diseases as an agonist of growth hormone secretagogue receptor (GHSR. GHSR was herein expressed in human gastric smooth muscle cells (HGSMCs and activated by ghrelin receptor agonist L-692,585. Like L-692,585, atractylodin also increased Ca2+ and enhanced the phosphorylation of myosin light chain (MLC through GHSR in HGSMCs. In addition, atractylodin promoted gastric emptying and MLC phosphorylation in the gastric antrum of mice also through GHSR. Collectively, atractylodin can activate GHSR in gastric smooth muscle, as a potential target in clinical practice.

  17. Diet and Nutrition in Cancer Survivorship and Palliative Care

    Directory of Open Access Journals (Sweden)

    Anthony J. Bazzan

    2013-01-01

    Full Text Available The primary goal of palliative cancer care is typically to relieve suffering and improve quality of life. Most approaches to diet in this setting have focused only on eating as many calories as possible to avoid cachexia. However, as the concept of palliative care has evolved to include all aspects of cancer survivorship and not just end of life care, there is an increasing need to thoughtfully consider diet and nutrition approaches that can impact not only quality of life but overall health outcomes and perhaps even positively affect cancer recurrence and progression. In this regard, there has been a recent emphasis in the literature on nutrition and cancer as an important factor in both quality of life and in the pathophysiology of cancer. Hence, the primary purpose of this paper is to review the current data on diet and nutrition as it pertains to a wide range of cancer patients in the palliative care setting.

  18. Molecular detection and characterization of Hop stunt viroid sequence variants from naturally infected pomegranate (Punica granatum L. in Tunisia

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    Faten GORSANE

    2010-09-01

    Full Text Available Tunisian pomegranate Hop stunt viroid (HSVd variants are described. Dot-blot hybridization, S-Page, and reverse transcription polymerase chain reaction (RT-PCR of RNA extracts from infected tissues were carried out. Results obtained by these techniques were confirmed by cDNA sequencing. The genetic diversity among the Tunisian variants was investigated, which also involved analysis of sequences of previously described HSVd variants from Tunisian citrus var. clementine and fig, and from fruit trees from other Mediterranean countries. Phylogenetic analysis showed that Tunisian pomegranate HSVd variants were clustered into two groups: a cachexia strain within the citrus type group and a recombinant citrus-plum type group. Results also showed a high haplotype diversity which was not related either to the host or to the geographical origin. Selective neutrality and genetic network tests suggest that the HSVd isolates have spread rapidly.

  19. Post-Traumatic Right Lumbar Abscess as First Manifestation of Perforated Right Colon Cancer - A Case Report.

    Science.gov (United States)

    Rossetto, Anna; Cerato, Franz; Cedolini, Carla; Arena, Maria Concetta; Bresadola, Vittorio; Terrosu, Giovanni

    2010-02-23

    Besides most common signs and symptoms suggesting a colic cancer, sometimes the clinical presentation can be difficult. Extra-abdominal abscess as a first sign of perforated colon carcinoma is a very unusual finding. We report a case of an old male patient, in bad general condition, with a post-traumatic finding of right lumbar abscess. After the percutaneous drainage with discharge of fecal material and a postponed explorative laparotomy, we discovered a perforated right colon carcinoma with a covered perforation affecting the duodenum wall and spreading to the hepatic bedand over to the back lumbar muscular wall. Because of the diffusion of the tumor, the patient was treated with palliative surgery with duodenum suture, right colon segment resection and subsequent ileocolic anastomosis with an uneventful postoperative course. The patient died 2 months later because of neoplastic cachexia.

  20. Post-Traumatic Right Lumbar Abscess as First Manifestation of Perforated Right Colon Cancer – A Case Report

    Science.gov (United States)

    Rossetto, Anna; Cerato, Franz; Cedolini, Carla; Arena, Maria Concetta; Bresadola, Vittorio; Terrosu, Giovanni

    2010-01-01

    Besides most common signs and symptoms suggesting a colic cancer, sometimes the clinical presentation can be difficult. Extra-abdominal abscess as a first sign of perforated colon carcinoma is a very unusual finding. We report a case of an old male patient, in bad general condition, with a post-traumatic finding of right lumbar abscess. After the percutaneous drainage with discharge of fecal material and a postponed explorative laparotomy, we discovered a perforated right colon carcinoma with a covered perforation affecting the duodenum wall and spreading to the hepatic bedand over to the back lumbar muscular wall. Because of the diffusion of the tumor, the patient was treated with palliative surgery with duodenum suture, right colon segment resection and subsequent ileocolic anastomosis with an uneventful postoperative course. The patient died 2 months later because of neoplastic cachexia. PMID:20740157

  1. Respiratory diseases and muscle dysfunction.

    Science.gov (United States)

    Gea, Joaquim; Casadevall, Carme; Pascual, Sergi; Orozco-Levi, Mauricio; Barreiro, Esther

    2012-02-01

    Many respiratory diseases lead to impaired function of skeletal muscles, influencing quality of life and patient survival. Dysfunction of both respiratory and limb muscles in chronic obstructive pulmonary disease has been studied in depth, and seems to be caused by the complex interaction of general (inflammation, impaired gas exchange, malnutrition, comorbidity, drugs) and local factors (changes in respiratory mechanics and muscle activity, and molecular events). Some of these factors are also present in cystic fibrosis and asthma. In obstructive sleep apnea syndrome, repeated exposure to hypoxia and the absence of reparative rest are believed to be the main causes of muscle dysfunction. Deconditioning appears to be crucial for the functional impairment observed in scoliosis. Finally, cachexia seems to be the main mechanism of muscle dysfunction in advanced lung cancer. A multidimensional therapeutic approach is recommended, including pulmonary rehabilitation, an adequate level of physical activity, ventilatory support and nutritional interventions.

  2. Atypical Presentation of Atypical Teratoid Rhabdoid Tumor in a Child

    Directory of Open Access Journals (Sweden)

    Y. T. Udaka

    2013-01-01

    Full Text Available Atypical Teratoid Rhabdoid Tumor (ATRT is a rare malignant intracranial neoplasm more commonly diagnosed in young children. The authors report the case of an 11-year-old boy with a long standing history of slowly progressive weight loss, fatigue, and weakness over 1.5 years whose magnetic resonance imaging revealed a large heterogeneous enhancing dorsally exophytic lower brainstem mass. Examination revealed extreme cachexia, gaze-evoked nystagmus, dysphagia, dysarthria, bilateral dysmetria, and global weakness without ambulation. The protracted history and neuroimaging features were most suggestive of a low grade glioma. However, pathology revealed a hypercellular tumor with large hyperchromatic nucleoli and loss of INI-1 staining on immunohistochemistry consistent with a diagnosis of an ATRT. The child died shortly after surgery due to complications from his brainstem infiltrative disease. This case illustrates the diverse presentation of ATRT in childhood that can clinically and radiographically mimic that of low grade glioma.

  3. Proposal of a Standard for the Condemnation for Turkey Carcasses Due to Fowlpox

    Directory of Open Access Journals (Sweden)

    BC Ferreira

    Full Text Available ABSTRACT This study aimed at proposing a new technical criteria for condemnation of turkey carcasses due to fowlpox in turkeys as a contribution for the work of the Brazilian Federal Meat Inspection Service. Skin samples from 30 carcasses of a flock of 840 turkeys (Meleagris gallopavo, previously vaccinated for fowlpox and slaughtered in June 2013, were collected. Samples were submitted to histological examination under light microscopy. The virus was identified using standard PCR techniques. The main histological findings were hyperplasia and hydropic degeneration of the epithelium and the presence of intracytoplasmic eosinophilic inclusion bodies. PCR results yielded 83.3% positive and 16.7% negative samples. Fowlpox virus is species specific, and there are no reports of its occurrence in mammals. The macroscopic and microscopic findings of the skin lesions do not justify the total condemnation of carcasses of poultry affected with fowlpox, except in cases of cachexia or repulsive appearance, as established by SIF regulation.

  4. Aorto-right ventricular fistula: a rare complication of Abiotrophia Endocarditis.

    Science.gov (United States)

    Bhattacharya, Priyanka; Mohammed, Aasim; Mizrahi, Eddy

    2017-07-01

    A 41-year-old African male presented with worsening dyspnea and cachexia concerning for congestive heart failure. Transesophageal echocardiogram revealed a large mass attached to the aortic valve leaflet, mass attached to the flail anterior mitral valve leaflet, severe pulmonary hypertension and dilatation of the aortic root along with fistula between the right coronary aortic cusp and the right ventricular (RV) outflow tract. Blood cultures grew Abiotrophia Defectiva (AD) sensitive to vancomycin. Patient underwent emergent surgical closure of aorto RV fistula and aortic root replacement along with pulmonary and mitral valve replacement. Endocarditis caused by AD has been reported to result in heart failure, septic embolization and destruction of the valve despite use of appropriate antibiotics. To our knowledge, this is the only case of AD endocarditis without any identified entrance route; requiring replacement of pulmonary, mitral and aortic valve due to extensive valvular damage and large vegetations.

  5. Microbiota and aging.

    Science.gov (United States)

    Bischoff, Stephan C

    2016-01-01

    This article summarizes our current knowledge of changes in the intestinal microbiota in elderly people and centenarians. Age-related processes comprise specific changes in the intestinal microbiota and related metabolic alterations. They result in 'inflamm-aging', which is associated with age-related inflammatory processes and diseases, including cachexia, frailty, canc