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.

  2. Cancer cachexia

    Directory of Open Access Journals (Sweden)

    Kunze Philipp

    2003-11-01

    Full Text Available Abstract In recent years many efforts of researchers and clinicians were made to improve our knowledge of cachexia syndrome. Not only cancer, but also many chronic or end-stage diseases such as AIDS, chronic obstructive pulmonary disease (COPD, rheumatoid arthritis, tuberculosis and Crohn's disease are associated with cachexia, a condition of abnormally low weight, weakness, and general bodily decline which deteriorates quality of life and reduces the prognosis of the patients who suffer from it. In the present editorial we will focus cachexia related on cancer and provide some insight into this prognosis-limiting syndrome.

  3. Pathophysiology of cancer cachexia

    OpenAIRE

    Younes Riad N.; Noguchi Yoshikazu

    2000-01-01

    Cancer cachexia is a frequent complication observed in patients with malignant tumors. Although several decades have passed since the first focus on the metabolic dysfunction's associated with cancer, few effective therapeutic interventions have been successfully introduced into the medical armamentarium. The present study thoroughly reviews the basic pathophysiology of cancer cachexia and the treatment options already investigated in that field. Experimental and clinical studies were evaluat...

  4. 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.

  5. Cancer Cachexia: One Step Ahead.

    Science.gov (United States)

    Meriggi, Fausto

    2015-01-01

    Cachexia is one of the most common manifestations in advanced cancer patients, but too often it remains under- recognized and under-treated. Starvation is not the same of cachexia. Cachexia is defined by "weight loss >5% over past 6 months in absence of simple starvation or the combination of ongoing weight loss>2% with BMI cachexia is not fully understood, but inflammation and an increased catabolic response to a number of cancer-related factors seem to represent the basis of any assumption. Early diagnosis of a pre-cachectic or cachectic state is a key moment for the treatment of this complex syndrome, in order to guarantee an adequate food intake and suitable exercise and to interfere with the inflammatory processes that are typical of cachexia. Therefore, one of the main aims is to identify those patients most likely to develop the syndrome early. A multimodality baseline approach to cancer cachexia addresses reversible clinical contributory factors. There are currently no medicinal products that have a proven efficacy in the medical approach to cancer cachexia. Recently, anamorelin, a synthetic orally active ghrelin receptor agonist, showed promising results, but the best approach to cancer cachexia probably remains an early multimodal interventions consisting in nutritional intervention, exercise and rehabilitation program, and multi-target drug therapies. This review summarizes what we know and what still need to know about cancer cachexia syndrome.

  6. Pathophysiology of cancer cachexia

    Directory of Open Access Journals (Sweden)

    Riad N. Younes

    2000-10-01

    Full Text Available Cancer cachexia is a frequent complication observed in patients with malignant tumors. Although several decades have passed since the first focus on the metabolic dysfunction's associated with cancer, few effective therapeutic interventions have been successfully introduced into the medical armamentarium. The present study thoroughly reviews the basic pathophysiology of cancer cachexia and the treatment options already investigated in that field. Experimental and clinical studies were evaluated individually in order to clarify the intricate alterations observed in tumor-bearing patients. The difficulties in introducing sound and effective nutritional support or metabolic manipulation to reverse cancer cachexia are outlined in this review.A caquexia é uma complicação freqüentemente observada em pacientes portadores de tumores malignos. Apesar de várias décadas transcorrerem desde a descrição inicial das disfunções metabólicas associadas ao câncer, poucas medidas terapêuticas foram induzidas com sucesso na prática médica. O presente estudo apresenta uma revisão detalhada da fisiopatologia básica da caquexia em câncer, e as opções terapêuticas desenvolvidas nesta área. Estudos experimentais, assim como clínicos, são avaliados individualmente para esclarecer as alterações complexas observadas em pacientes portadores de tumores. As dificuldades encontradas para introduzir manipulações metabólicas e terapias de suporte nutricional eficientes são discutidas nesta revisão.

  7. Update on anorexia and cachexia.

    Science.gov (United States)

    Strasser, Florian; Bruera, Eduardo D

    2002-06-01

    Declining physical, emotional, and social function as a result of anorexia and cachexia are considerable contributors to discomfort for cancer patients and their families, and they impair the patient's ability to express optimal physical and psychosocial potential as long as possible. This decline no longer has to be accepted as an indispensable sequel to advanced cancer, just as pain is no longer considered to be unavoidable. A routine screening for anorexia and cachexia and associated symptoms is necessary, as is a careful, comprehensive assessment, because the condition is not always obvious. Decisions about anorexia and cachexia treatment are guided by prioritizing the different, concurrent physical, psychosocial, and existential problems and by considering the natural course of the cancer and the effects of antineoplastic therapies. Reversible causes for anorexia and cachexia need to be identified and treated, if appropriate. Nutritional interventions are often indicated; patients with a predominant starvation component and without inflammation may profit the most. New pharmacologic therapies for primary anorexia and cachexia syndrome are expected to enter clinical practice soon; however, until then, treatment with corticosteroids, progestins, or prokinetics may be indicated for some patients. To understand a multicausal syndrome, multimodal and interdisciplinary therapy is required. Specialist palliative care services can be helpful to provide, hand-in-hand with the disease specialists [172], assessment and management of psychophysical symptoms and sociospiritual needs of patients during the course of the illness and at the end of life [173]. Research efforts aim to better characterize subgroups of patients suffering from secondary causes of anorexia and cachexia and to elucidate the mechanisms involved in the primary anorexia and cachexia syndrome. Increasingly individualized treatments are expected with combination treatments that involve different

  8. Cancer cachexia, mechanism and treatment

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

    It is estimated that half of all patients with cancereventually develop a syndrome of cachexia, with anorexiaand a progressive loss of adipose tissue and skeletalmuscle mass. Cancer cachexia is characterized by systemicinflammation, negative protein and energy balance, andan involuntary loss of lean body mass. It is an insidioussyndrome that not only has a dramatic impact on patientquality of life, but also is associated with poor responsesto chemotherapy and decreased survival. Cachexia isstill largely an underestimated and untreated condition,despite the fact that multiple mechanisms are reported tobe involved in its development, with a number of cytokinespostulated to play a role in the etiology of the persistentcatabolic state. Existing therapies for cachexia, includingorexigenic appetite stimulants, focus on palliation ofsymptoms and reduction of the distress of patients andfamilies rather than prolongation of life. Recent therapiesfor the cachectic syndrome involve a multidisciplinaryapproach. Combination therapy with diet modificationand/or exercise has been added to novel pharmaceuticalagents, such as Megestrol acetate, medroxyprogesterone,ghrelin, omega-3-fatty acid among others. These agentsare reported to have improved survival rates as well asquality of life. In this review, we will discuss the emergingunderstanding of the mechanisms of cancer cachexia,the current treatment options including multidisciplinarycombination therapies, as well an update on new andongoing clinical trials.

  9. Cachexia, malnutrition, the refeeding syndrome, and lessons from Goldilocks.

    Science.gov (United States)

    Palesty, J Alexander; Dudrick, Stanley J

    2011-06-01

    Cachexia has plagued clinicians for centuries. Although all cachexia is related to malnutrition, cachexia associated with malignant diseases differs from starvation cachexia in that it is more recalcitrant to nutritional therapy. All cachexia responds to judicious nutritional support; however, cancer cachexia worsens autonomously as the disease advances and cannot be arrested or reversed by any known form of nutrition, hormonal, or pharmacologic therapy. Cachexia must be treated cautiously to avoid overfeeding syndrome, which may result in serious or dangerous complications or death.

  10. 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.

  11. 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.

  12. 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.

  13. 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. Skel

  14. Mechanisms and treatment of cancer cachexia.

    Science.gov (United States)

    Argilés, J M; López-Soriano, F J; Busquets, S

    2013-12-01

    According to a recent consensus, cachexia is a complex metabolic syndrome associated with underlying illness and characterised 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 terminal cancer patients and it is responsible for the deaths of 22% of cancer patients. Although body weight is, indeed, an important factor to be taken into consideration in 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 therapeutical combination are two: an anticatabolic aim directed towards both fat and muscle catabolism and an anabolic objective leading to the synthesis of macromolecules such as contractile proteins.

  15. Molecular and neuroendocrine mechanisms of cancer cachexia.

    Science.gov (United States)

    Mendes, Maria Carolina S; Pimentel, Gustavo D; Costa, Felipe O; Carvalheira, José B C

    2015-09-01

    Cancer and its morbidities, such as cancer cachexia, constitute a major public health problem. Although cancer cachexia has afflicted humanity for centuries, its underlying multifactorial and complex physiopathology has hindered the understanding of its mechanism. During the last few decades we have witnessed a dramatic increase in the understanding of cancer cachexia pathophysiology. Anorexia and muscle and adipose tissue wasting are the main features of cancer cachexia. These apparently independent symptoms have humoral factors secreted by the tumor as a common cause. Importantly, the hypothalamus has emerged as an organ that senses the peripheral signals emanating from the tumoral environment, and not only elicits anorexia but also contributes to the development of muscle and adipose tissue loss. Herein, we review the roles of factors secreted by the tumor and its effects on the hypothalamus, muscle and adipose tissue, as well as highlighting the key targets that are being exploited for cancer cachexia treatment.

  16. Cancer Cachexia: Muscle Physiology and Exercise Training

    Directory of Open Access Journals (Sweden)

    Matthew L. Goodwin

    2012-11-01

    Full Text Available Cachexia in cancer patients is a condition marked by severe tissue wasting and a myriad of quality of life and health consequences. Cachexia is also directly linked to the issues of morbidity and survivability in cancer patients. Therapeutic means of mitigating cachexia and its effects are thus critical in cancer patient treatment. We present a discussion on the use of physical exercise activities in the context of such treatment as a means to disruption the tissue wasting effects (i.e., muscle tissue losses via anorexigenic pro-inflammatory cytokines of cachexia. In addition we propose a theoretical model (Exercise Anti-Cachectic Hypothetical—“EACH” model as to how exercise training may promote a disruption in the cycle of events leading to advancing cachexia and in turn promote an enhanced functionality and thus improved quality of life in cancer patients.

  17. Cardiac Cachexia: Perspectives for Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Marina Politi Okoshi

    Full Text Available Abstract 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.

  18. 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. PMID:27812676

  19. Cancer Cachexia and MicroRNAs.

    Science.gov (United States)

    Camargo, Rodolfo Gonzalez; Quintas Teixeira Ribeiro, Henrique; Geraldo, Murilo Vieira; Matos-Neto, Emídio; Neves, Rodrigo Xavier; Carnevali, Luiz Carlos; Donatto, Felipe Fedrizzi; Alcântara, Paulo S M; Ottoch, José P; Seelaender, Marília

    2015-01-01

    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. Treating cancer cachexia to treat cancer

    Directory of Open Access Journals (Sweden)

    Lee Se-Jin

    2011-01-01

    Full Text Available Abstract Skeletal muscle wasting is a major component of cachectic states found in a variety of disease settings, including cancer. As increasing caloric intake often provides little benefit in combating muscle loss in cachectic patients, a major research focus has been to develop strategies stimulating muscle anabolic pathways - in an attempt to fight the catabolic pathways induced during cachexia. Two recent papers have reported the beneficial effects of blocking the myostatin/activin signalling pathway in mouse models of cancer cachexia. We discuss the implications of their findings both with respect to the role that this signalling pathway may play in the aetiology of cachexia and with respect to the prospects for targeting this pathway as a therapeutic strategy in patients with cachexia.

  1. Nutrition in cachexia: from bench to bedside.

    Science.gov (United States)

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

    2016-05-01

    As malnutrition is often present in cachexia, nutritional intervention has been one of the widely accepted strategies. A literature review of cachexia models with dietary interventions in the present issue of this journal pointed out that the majority of nutrient intervention studies were of n-3 fatty acid, mainly eicosapentaenoic acid and docosahexaenoic acid. Effect on protein catabolism and anti-inflammation are most pronounced benefits of n-3 fatty acid. The effectiveness of n-3 fatty acid may depend on control diet or even be attributed to the polyunsaturated fatty acid deficiency inadvertently produced in control group. However, there is not enough clinical evidence to support a benefit of n-3 fatty acid substitution in patients with cachexia. The second important result from this review is that the majority of studies did not provide information about dietary design or did not standardize design, content, source, and overall composition. To guide dietary design for researchers in preclinical studies, a model has been proposed in this review, which may be useful to predict the efficacy of new dietary intervention in cachexia science. From a clinical point of view, the limited effectiveness of nutritional support in cachexia may partly be explained by the multifactorial nature of this condition. Cachexia differs from malnutrition inasmuch as malnutrition can be reversed by adequate nutrition and/or by overcoming problems of absorption or utilization of nutrients, but cachexia cannot be successfully treated by nutrition alone. Multidisciplinary approach including the assessment and intervention in feeding, appetite, swallowing, exercise, psychosocial, and psychological issue may be needed to improve nutrition in patients with cachexia.

  2. Adipokines and ghrelin in gastric cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    Mustafa Kerem; Zafer Ferahkose; Utku Tonguc Yilmaz; Hatice Pasaoglu; Ebru Ofluoglu; Abdulkadir Bedirli; Bulent Salman; Tevfik Tolga Sahin; Murat Akin

    2008-01-01

    AIM: To investigate the roles of the adipocytokines, ghrelin and leptin in gastric cancer cachexia.METHODS: Resistin, ghrelin, leptin, adiponectin, insulin and insulin-like growth factor (IGF-I), were measured in 30 healthy subjects, and 60 gastric cancer patients of which 30 suffered from cancer- induced cachexia and 30 served as a control group. The relationships between hormones, body mass index (BMI) loss ratio, age, gender, and Glasgow Prognostic Score (GPS) were investigated.RESULTS: Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients (P<0.05). Ghrelin, resistin, leptin, adiponectin and IGF-I, showed a significant correlation with BMI loss ratio and GPS (P < 0.05). A strong correlation was seen between GPS and BMI loss (R = -0.570, P < 0.0001). Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin, resistin, leptin and IGF-I (P<0.05). Existence of an important significant relationship between resistin and insulin resistance was also noted.CONCLUSION: These results showed that serum ghrelin, leptin, adiponectin, and IGF-I play important roles in cachexia-related gastric cancers. No relationship was found between resistin and cancer cachexia. Also, because of the correlation between these parameters and GPS, these parameters might be used as a predictor factor.

  3. Estimation of Cachexia among Cancer Patients Based on Four Definitions

    OpenAIRE

    2009-01-01

    Objectives. Estimate and compare the proportion of cancer patients with cachexia using different definitions from available clinical data. Methods. Electronic medical records were examined to estimate the proportion of cancer patients with cachexia using 4 definitions: (1) ICD-9 diagnostic code of 799.4 (cachexia), (2) ICD-9 diagnosis of cachexia, anorexia, abnormal weight loss, or feeding difficulties, (3) prescription for megestrol acetate, oxandrolone, somatropin, or dronabinol, and (4) ≥ ...

  4. Animal models of anorexia and cachexia

    Science.gov (United States)

    DeBoer, Mark Daniel

    2009-01-01

    Background Cachexia is a devastating syndrome of body wasting that worsens quality of life and survival for patients suffering from diseases such as cancer, chronic kidney disease and chronic heart failure. Successful treatments have been elusive in humans, leaving a clear need for the development of new treatment compounds. Animal models of cachexia are able to recapitulate the clinical findings from human disease and have provided a much-needed means of testing the efficacy of prospective therapies. Objective This review focuses on animal models of cachexia caused by cancer, chronic heart failure and chronic kidney disease, including the features of these models, their implementation, and commonly-followed outcome measures. Conclusion Given a dire clinical need for effective treatments of cachexia, animal models will continue a vital role in assessing the efficacy and safety of potential treatments prior to testing in humans. Also important in the future will be the use of animal models to assess the durability of effect from anti-cachexia treatments and their effect on prognosis of the underlying disease states. PMID:20160874

  5. Exercise training as treatment in cancer cachexia.

    Science.gov (United States)

    Lira, Fábio Santos; Neto, José Cesar Rosa; Seelaender, Marília

    2014-06-01

    Cachexia is a wasting syndrome that may accompany a plethora of diseases, including cancer, chronic obstructive pulmonary disease, aids, and rheumatoid arthritis. It is associated with central and systemic increases of pro-inflammatory factors, and with decreased quality of life, response to pharmacological treatment, and survival. At the moment, there is no single therapy able to reverse cachexia many symptoms, which include disruption of intermediary metabolism, endocrine dysfunction, compromised hypothalamic appetite control, and impaired immune function, among other. Growing evidence, nevertheless, shows that chronic exercise, employed as a tool to counteract systemic inflammation, may represent a low-cost, safe alternative for the prevention/attenuation of cancer cachexia. Despite the well-documented capacity of chronic exercise to counteract sustained disease-related inflammation, few studies address the effect of exercise training in cancer cachexia. The aim of the present review was hence to discuss the results of cachexia treatment with endurance training. As opposed to resistance exercise, endurance exercise may be performed devoid of equipment, is well tolerated by patients, and an anti-inflammatory effect may be observed even at low-intensity. The decrease in inflammatory status induced by endurance protocols is paralleled by recovery of various metabolic pathways. The mechanisms underlying the response to the treatment are considered.

  6. 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.

  7. Cancer cachexia: towards integrated therapeutic interventions.

    Science.gov (United States)

    Molfino, Alessio; Formiconi, Alessandra; Rossi Fanelli, Filippo; Muscaritoli, Maurizio

    2014-10-01

    Biological treatments represent a novel approach to counteract cancer cachexia. Monoclonal antibodies targeting cytokines and molecules responsible for muscle wasting, with an anti-inflammatory effect, however, still have several limitations and need further clinical investigation. New research in this field will contribute to the better understanding of the multifactorial pathogenesis of cancer cachexia, while favoring the consolidation of multimodal preventive and therapeutic strategies encompassing nutritional and pharmacological treatments. New pharmacological therapies and conventional nutritional treatments will soon integrate in the 'parallel pathway', aimed at early recognition, prevention and treatment of the metabolic and nutritional derangements occurring in cancer. This will likely produce improvement in quality of life, tolerance to treatments and survival.

  8. Megestrol acetate in cachexia and anorexia

    Science.gov (United States)

    Yeh, Shing-shing; Schuster, Michael W

    2006-01-01

    The aim is to review major clinical trials that have used megestrol acetate (MA) in the treatment of cachexia across several disease states. A review of general usage and potential side-effects are discussed. A theory that the newly approved nanocrystal formation of MA can better deliver this potent medication for treatment will also be reviewed. PMID:17722275

  9. 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.

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

    OpenAIRE

    2014-01-01

    Background 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 lev...

  11. Pancreatic cancer cachexia: A review of mechanisms and therapeutics

    Directory of Open Access Journals (Sweden)

    Carlyn Rose Tan

    2014-03-01

    Full Text Available Over the last decade, we have gained new insight into the pathophysiology of pancreatic cancer cachexia. 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.

  12. The wasting continuum in heart failure: from sarcopenia to cachexia.

    Science.gov (United States)

    von Haehling, Stephan

    2015-11-01

    Sarcopenia (muscle wasting) and cachexia share some pathophysiological aspects. Sarcopenia affects approximately 20 %, cachexia cachexia means loss of muscle and fat tissue that leads to weight loss. The wasting continuum in HF implies that skeletal muscle is lost earlier than fat tissue and may lead from sarcopenia to cachexia. Both tissues require conservation, and therapies that stop the wasting process have tremendous therapeutic appeal. The present paper reviews the pathophysiology of muscle and fat wasting in HF and discusses potential treatments, including exercise training, appetite stimulants, essential amino acids, growth hormone, testosterone, electrical muscle stimulation, ghrelin and its analogues, ghrelin receptor agonists and myostatin antibodies.

  13. 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.

  14. [Pharmacological therapy of cancer anorexia-cachexia].

    Science.gov (United States)

    Cardona, D

    2006-05-01

    Anorexia is one of the most common symptoms of patients with advanced cancer and it presents as loss of appetite due to satiety. On the other hand, cachexia is described in those patients with unwanted weight loss. Cancerous processes produce an energy unbalance by decreased food intake and increased catabolism, resulting in a clearly negative balance. Several factors determining cachexia are observed, from metabolic unbalances produced by tumoral products and endocrine impairments or the inflammatory response produced by cytokines, all of them leading to higher lipolysis, loss of muscle protein, and anorexia. Besides, causes of anorexia are multiple, from chemotherapy agents, radiotherapy, or immunotherapy, which may produce different degrees of nausea, vomiting, diarrhea, and also leading to impairments of taste and smell, to obstruction of the digestive tract, pain, depression, constipation, etc. From the knowledge of the different mechanisms producing the anorexia-cachexia syndrome, hypercaloric diets for artificial nutrition have been studied with varying success, and different drugs with a positive effect on appetite gain such as progestogens, steroids, and with lesser clinical evidence cannabinoids, cyproheptadine, mirtazapine (antidepressant), and olanzapine (antipsychotic). Other drugs have been studied because of their anti-inflammatory properties, anti-cytokine, such as melatonin, polyunsaturated omega-3 fatty acids, pentoxifylline, and thalidomide; with the exception of the latter, clinical data are still scant for daily usage. Similarly happens with testosterone-derived anabolic drugs or with metabolism inhibitors such as hydrazine sulfate. With no doubt, progestogens, especially megestrol, and corticosteroids will be first-line therapies for anorexia-cachexia syndrome to stimulate the appetite and increase weight (megestrol), and have an effect on quality of life improvement and comfort in patients with advanced cancer.

  15. The syndrome of anorexia-cachexia.

    Science.gov (United States)

    Body, J J

    1999-07-01

    Cancer anorexia/cachexia is a major clinical problem, especially in advanced cancer patients. Its pathogenesis is quite complex. Anorexia plays a central role, but cancer cachexia is more complex than pure chronic starvation. One of the key differences is the preferential mobilization of fat and the sparing of skeletal muscle in simple starvation compared with an equal mobilization of fat and skeletal muscle in cancer patients. An increase in basal energy expenditures seems to play a contributory role in many patients. Cytokines, essentially but not exclusively tumor necrosis factor alpha, play an essential role, and the syndrome can be compared with a low-grade chronic inflammatory state. As it is in most fields in medicine, prevention is more efficacious than treatment, and, to avoid the final and dramatic stages of cancer cachexia, adequate nutritional advice and support must be provided sufficiently early. Parenteral nutrition could facilitate the administration of complete doses of chemotherapy or radiotherapy, but no significant survival benefit or decrease in treatment-induced toxicity have ever been demonstrated in prospective randomized trials. The gut should always be used if at all possible. Percutaneous endoscopic gastrostomy is used increasingly in patients who cannot eat but who have functionally intact gastrointestinal tracts, especially in patients with head and neck cancer. Eight randomized, double-blind, placebo-controlled studies have demonstrated that progestational drugs can somewhat stimulate appetite, food intake, and energy level; increase weight in many patients; and often decrease nausea and vomiting severity; however, pharmacologic treatment of cancer cachexia remains disappointing, and more trials with anticytokine drugs should be conducted.

  16. Estimation of Cachexia among Cancer Patients Based on Four Definitions

    Directory of Open Access Journals (Sweden)

    Kathleen M. Fox

    2009-01-01

    Full Text Available Objectives. Estimate and compare the proportion of cancer patients with cachexia using different definitions from available clinical data. Methods. Electronic medical records were examined to estimate the proportion of cancer patients with cachexia using 4 definitions: (1 ICD-9 diagnostic code of 799.4 (cachexia, (2 ICD-9 diagnosis of cachexia, anorexia, abnormal weight loss, or feeding difficulties, (3 prescription for megestrol acetate, oxandrolone, somatropin, or dronabinol, and (4 ≥5% weight loss. Patients with cancer of the stomach, pancreas, lung, colon/rectum, head/neck, esophagus, prostate, breast, or liver diagnosed between 1999 and 2004 were followed for cachexia. Results. Of 8541 cancer patients (60% men and 55% Caucasian, cachexia was observed in 2.4% of patients using the cachexia diagnostic code, 5.5% expanded diagnoses, 6.4% prescription medication definition, and 14.7% with ≥5% weight loss. Conclusions. The proportion of patients with cachexia varied considerably depending upon the definition employed, indicating that a standard operational definition is needed.

  17. 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.

  18. Cachexia and pancreatic cancer: are there treatment options?

    Science.gov (United States)

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

    2014-07-28

    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.

  19. Definition and classification of cancer cachexia: an international consensus.

    Science.gov (United States)

    Fearon, Kenneth; Strasser, Florian; Anker, Stefan D; Bosaeus, Ingvar; Bruera, Eduardo; Fainsinger, Robin L; Jatoi, Aminah; Loprinzi, Charles; MacDonald, Neil; Mantovani, Giovanni; Davis, Mellar; Muscaritoli, Maurizio; Ottery, Faith; Radbruch, Lukas; Ravasco, Paula; Walsh, Declan; Wilcock, Andrew; Kaasa, Stein; Baracos, Vickie E

    2011-05-01

    To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management.

  20. 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.

  1. 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.

  2. Diabetic neuropathic cachexia: report of a recurrent case

    OpenAIRE

    Jackson, C; R. Barohn

    1998-01-01

    Diabetic neuropathic cachexia is an uncommon peripheral neuropathy associated with diabetes mellitus and characterised by profound weight loss and painful dysaesthesias over the limbs and trunk. The pathophysiological basis of this disorder remains unknown and there have been no published cases of recurrent episodes. A hispanic man who experienced two episodes of diabetic neuropathic cachexia over a seven year period is described.



  3. The complex liaison between cachexia and tumor burden (Review).

    Science.gov (United States)

    De Lerma Barbaro, Andrea

    2015-10-01

    Cachexia is a wasting syndrome that afflicts end-stage cancer patients. Whereas a consensus statement for a definition of cachexia recently has been accomplished, a useful measurement for this condition at present is lacking. The aim of the present review is to discuss the advantage of introducing the measurement of tumor burden for a better overall evaluation of cachexia. Our suggestion ensues from a somewhat novel perspective in the field of infectious disease research where a careful measurement of the pathogen load, between i.e. different host genotypes, leads to the definition of the concept of tolerance to the infectious insult. Indeed tolerance concurs, together the more classical resistance, in maintaining the host reproductive fitness or health state. Noticeably a similar reasoning may apply to tumor biology as well. Whereas the extent of cachexia increases with tumor burden, the relationship between these two correlates of tumor progression fluctuates in a broad range. We have selected from the literature studies in the rodent model where significant variation in the course of the wasting illness during cancer was observed and quantitatively assessed comparing experimental groups marked by different genotype, drug treatment, diet or gender. These studies may be further classified in two categories: the former where the experimental condition associated to milder cachexia is accompanied to a lesser tumor burden, the latter where the inhibition of cachexia results disentangled from the tumor burden, that is the whole number of cancer cells results unchanged or even, paradoxically, is increased. In addition we survey, even in the context of human malignancy, the significance and feasibility of plotting quantitative estimates of cachexia against the whole tumor burden. Ultimately, the principal endeavor of introducing the measurement of tumor burden, in both experimental and clinical oncology, may be to achieve a better assessment of the inter

  4. Caquexia cardíaca Cardiac cachexia

    Directory of Open Access Journals (Sweden)

    Alberto Miján

    2006-05-01

    .Chronic heart failure (CHF, especially affecting the right heart, frequently leads to malnutrition. If the latter is severe and is combined to other factors, it may lead to cardiac cachexia. This one is associated to increased mortality and lower survival of patients suffering from it. The causes of cardiac cachexia are diverse, generally associated to maintenance of a negative energy balance, with increasing evidence of its multifactorial origin. Neurohumoral, inflammatory, immunological, and metabolic factors, among others, are superimposed in the patient with CHF, leading to involvement and deterioration of several organs and systems, since this condition affects both lean (or active cellular mass and adipose and bone tissue - osteoporosis. Among all, the most pronounced deterioration may be seen at skeletal muscle tissue, at both structural and functional levels, the heart not being spared. As for treatment, it should be based on available scientific evidence. Assessment of nutritional status of any patient with CHF is a must, with the requirement of nutritional intervention in case of malnutrition. In this situation, especially if accompanied by cardiac cachexia, it is required to modify energy intake and oral diet quality, and to consider the indication of specific complementary or alternative artificial nutrition. Besides, the causal relationship of the beneficial role of moderate physical exertion is increasing, as well as modulation of metabolic and inflammatory impairments observed in cardiac cachexia with several drugs, leading to a favorable functional and structural response in CHF patients.

  5. Counteracting inflammation: a promising therapy in cachexia.

    Science.gov (United States)

    Argiles, Josep M; Lopez-Soriano, Francisco J; Busquets, Silvia

    2012-01-01

    Disease progression in cancer is dependent on the complex interaction between the tumor and the host inflammatory response. Indeed, both the tumor and the patient produce cytokines that act on multiple target sites such as bone marrow, myocytes, hepatocytes, adipocytes, endothelial cells, and neurons, where they produce a complex cascade of biological responses leading to the wasting associated with cachexia. The cytokines that have been involved in this cachectic response are TNF-α, IL-1, IL-6, and interferon-gamma. Interestingly, these cytokines share the same metabolic effects, and their activities are closely interrelated. In many cases these cytokines exhibit synergic effects when administered together. Therefore, therapeutic strategies- either nutritional or pharmacological-have been based on either blocking their synthesis or their action.

  6. Skeletal muscle regeneration in cancer cachexia.

    Science.gov (United States)

    Bossola, Maurizio; Marzetti, Emanuele; Rosa, Fausto; Pacelli, Fabio

    2016-05-01

    Muscle wasting is the most important phenotypic and clinical feature of cancer cachexia, and the principal cause of impaired physical function, fatigue, and respiratory complications. Muscle loss has been attributed to a variable combination of reduced nutritional intake and an imbalance between anabolic and catabolic processes. It has been suggested that defective skeletal muscle regeneration may also contribute to muscle wasting in cancer patients. However, there is little in vitro or in vivo data available, in either animals or in humans, regarding skeletal muscle regeneration in cancer wasting. The aim of the present review is to define the role of skeletal muscle regeneration in the muscle wasting of cancer patients and to determine possible therapeutic implications.

  7. Differential Bone Loss in Mouse Models of Colon Cancer Cachexia

    Science.gov (United States)

    Bonetto, Andrea; Kays, Joshua K.; Parker, Valorie A.; Matthews, Ryan R.; Barreto, Rafael; Puppa, Melissa J.; Kang, Kyung S.; Carson, James A.; Guise, Theresa A.; Mohammad, Khalid S.; Robling, Alexander G.; Couch, Marion E.; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2017-01-01

    Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and ApcMin/+. The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the ApcMin/+ mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia. PMID:28123369

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

    Science.gov (United States)

    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.

  9. The prognostic role of inflammation and hormones in patients with metastatic cancer with cachexia.

    Science.gov (United States)

    Bilir, Cemil; Engin, Huseyin; Can, Murat; Temi, Yasemin Bakkal; Demirtas, Derya

    2015-03-01

    We wanted to investigate the possible etiologic factors of cachexia. Forty-six patients diagnosed with cancer cachexia and 34 healthy controls were included in the study. Serum total testosterone, free testosterone, interleukin 1 (IL) alpha and beta, IL6, tumor necrosis factor (TNF) alpha, orexin, galanin, neuropeptide Y, tumor necrosis factor-like weak inducer of apoptosis and tumor necrosis factor receptor-associated factor 6, and C-reactive protein (CRP) levels were investigated. There were 36 male and 10 female patients in the cachexia group, and 24 male and 10 female patients in the control group. Median overall survival (OS) of the cachexia group after the diagnosis of cachexia was 8 (1-25) months. There were statistically significant relationships between OS and BMI, serum CRP, TRAF-6, albumin, and LDH levels in the cachexia group. In addition to cachexia, serum CRP, testosterone, and TNF alpha levels were statistically significantly correlated with OS in refractory cachexia. TRAF-6 levels was significantly correlated with type of cancer (P = 0.02). Although cachexia presents with a multifactorial ethio-pathogenesis, few of them affect the OS. Our novel results were that serum CRP, albumin, LDH, and TRAF-6 levels have a higher association with OS in patients with cancer cachexia compared to the many other parameters. An ongoing cachexia also called refractory cachexia is a recent definition. This end-stage term of cancer duration may be predicted by decreasing serum testosterone and increasing serum TNF alpha levels, as well as serum CRP levels.

  10. Optimal management of cancer anorexia–cachexia syndrome

    Directory of Open Access Journals (Sweden)

    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

  11. Heterogeneous response of adipose tissue to cancer cachexia

    Directory of Open Access Journals (Sweden)

    P.S. Bertevello

    2001-09-01

    Full Text Available Cancer cachexia causes disruption of lipid metabolism. Since it has been well established that the various adipose tissue depots demonstrate different responses to stimuli, we assessed the effect of cachexia on some biochemical and morphological parameters of adipocytes obtained from the mesenteric (MES, retroperitoneal (RPAT, and epididymal (EAT adipose tissues of rats bearing Walker 256 carcinosarcoma, compared with controls. Relative weight and total fat content of tissues did not differ between tumor-bearing rats and controls, but fatty acid composition was modified by cachexia. Adipocyte dimensions were increased in MES and RPAT from tumor-bearing rats, but not in EAT, in relation to control. Ultrastructural alterations were observed in the adipocytes of tumor-bearing rat RPAT (membrane projections and EAT (nuclear bodies.

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

    Science.gov (United States)

    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.

  13. 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

  14. Opportunities for targeting the fatigue-anorexia-cachexia symptom cluster.

    Science.gov (United States)

    Alesi, Erin R; del Fabbro, Egidio

    2014-01-01

    Cancer patients experience multiple symptoms throughout their illness trajectory. Symptoms consistently occurring together, known as symptom clusters, share common pathophysiologic mechanisms. Understanding and targeting such symptom clusters may allow for more effective and efficient use of treatments for a variety of symptoms. Fatigue-anorexia-cachexia is one of the most prevalent symptom clusters and significantly impairs quality of life. In this review, we explore the fatigue-anorexia-cachexia symptom cluster and focus on current and emerging therapies with an emphasis on pharmacologic management.

  15. Mechanisms of metabolic dysfunction in cancer-associated cachexia.

    Science.gov (United States)

    Petruzzelli, Michele; Wagner, Erwin F

    2016-03-01

    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.

  16. [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.

  17. Serum interleukin-15 levels in cancer patients with cachexia.

    Science.gov (United States)

    Martínez-Hernández, Pedro L; Hernanz-Macías, Ángel; Gómez-Candela, Carmen; Grande-Aragón, Cristina; Feliu-Batlle, Jaime; Castro-Carpeño, Javier; Martínez-Muñoz, Isabel; Zurita-Rosa, Laura; Villarino-Sanz, Marta; Prados-Sánchez, Concepción; Sánchez García-Girón, Joaquín

    2012-10-01

    Interleukin-15 (IL-15) has important anabolic effects on muscle protein metabolism through a decrease in the ATP-ubiquitin-dependent proteolytic pathway. The role of IL-15 in human cancer cachexia is unknown. The aim of this study was to assess the relationship between interleukin-15 (IL-15) in cancer patients with cachexia at diagnosis of malignancy and 8 weeks later. An observational study of 21 cancer patients (with and without cachexia) and 8 healthy subjects was conducted. Body composition was measured by leg-to-leg impedance. Serum IL-15 levels were assessed at baseline and after 4 and 8 weeks. Baseline IL-15 values were similar in cancer patients and in healthy subjects. Cancer patients with lower baseline levels of IL-15 (cancer cachexia pathogenesis, the association during evolution between serum IL-15 and changes in weight and muscle mass suggests a possible role of IL-15 as a marker of the body composition response in cancer patients who are losing weight at the time of diagnosis.

  18. 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.

  19. Cachexia and sarcopenia: mechanisms and potential targets for intervention.

    Science.gov (United States)

    Argilés, Josep M; Busquets, Silvia; Stemmler, Britta; López-Soriano, Francisco J

    2015-06-01

    Cachexia is a multi-organ syndrome associated with cancer and other chronic diseases, characterized by body weight loss, muscle and adipose tissue wasting and inflammation, being often associated with anorexia. Skeletal muscle tissue represents more than 40% of body weight and seems to be one of the main tissues involved in the wasting that occurs during cachexia. Sarcopenia is a degenerative loss of skeletal muscle mass, quality, and strength associated with healthy ageing. The molecular mechanisms behind cachexia and sarcopenia share some common trends. Muscle wasting is the result of a combination of an imbalance between synthetic and degradative protein pathways together with increased myocyte apoptosis and decreased regenerative capacity. Oxidative pathways are also altered in skeletal muscle during muscle wasting and this seems to be a consequence of mitochondrial abnormalities that include altered morphology and function, decreased ATP synthesis and uncoupling. The aim of the present review is to analyse common molecular pathways between cachexia and sarcopenia in order to put forward potential targets for intervention.

  20. Cachexia in patients with chronic pancreatitis and pancreatic cancer: impact on survival and outcome.

    Science.gov (United States)

    Bachmann, Jeannine; Büchler, Markus W; Friess, Helmut; Martignoni, Marc E

    2013-01-01

    Chronic pancreatitis (CP) and pancreatic adenocarcinoma (PDAC) are the most common diseases of the pancreas. Cachexia-weight loss exceeding 10% of stable body weight-is present in up to 80% of patients with PDAC. Because the mechanisms of cachexia are not well known, this provides a possibility to compare clinical courses of benign and malignant cachexia. In this study, 382 patients-242 with a PDAC stage UICC II/ 140 with CP-were documented regarding the prevalence of cachexia and its influence on perioperative morbidity and mortality with a special interest to postoperative weight gain and survival. Cachexia was present in 41.4% of CP and 31% of cancer patients. We could demonstrate more pronounced systemic effects of cachexia in patients with PDAC. Weight loss was faster in PDAC patients, the amount of weight loss did not differ significantly between the groups. Cachexia had a significant impact on survival and the postoperative course in patients with PDAC and tumor resection. The development of cachexia is faster in patients with a malignant disease and the systemic effects are more pronounced. Therefore, tumor cachexia should be considered as a different entity than cachexia in benign diseases.

  1. Skeletal muscle mitochondrial uncoupling in a murine cancer cachexia model.

    Science.gov (United States)

    Tzika, A Aria; Fontes-Oliveira, Cibely Cristine; Shestov, Alexander A; Constantinou, Caterina; Psychogios, Nikolaos; Righi, Valeria; Mintzopoulos, Dionyssios; Busquets, Silvia; Lopez-Soriano, Francisco J; Milot, Sylvain; Lepine, Francois; Mindrinos, Michael N; Rahme, Laurence G; Argiles, Josep M

    2013-09-01

    Approximately half of all cancer patients present with cachexia, a condition in which disease-associated metabolic changes lead to a severe loss of skeletal muscle mass. Working toward an integrated and mechanistic view of cancer cachexia, we investigated the hypothesis that cancer promotes mitochondrial uncoupling in skeletal muscle. We subjected mice to in vivo phosphorous-31 nuclear magnetic resonance (31P NMR) spectroscopy and subjected murine skeletal muscle samples to gas chromatography/mass spectrometry (GC/MS). The mice used in both experiments were Lewis lung carcinoma models of cancer cachexia. A novel 'fragmented mass isotopomer' approach was used in our dynamic analysis of 13C mass isotopomer data. Our 31P NMR and GC/MS results indicated that the adenosine triphosphate (ATP) synthesis rate and tricarboxylic acid (TCA) cycle flux were reduced by 49% and 22%, respectively, in the cancer-bearing mice (p<0.008; t-test vs. controls). The ratio of ATP synthesis rate to the TCA cycle flux (an index of mitochondrial coupling) was reduced by 32% in the cancer-bearing mice (p=0.036; t-test vs. controls). Genomic analysis revealed aberrant expression levels for key regulatory genes and transmission electron microscopy (TEM) revealed ultrastructural abnormalities in the muscle fiber, consistent with the presence of abnormal, giant mitochondria. Taken together, these data suggest that mitochondrial uncoupling occurs in cancer cachexia and thus point to the mitochondria as a potential pharmaceutical target for the treatment of cachexia. These findings may prove relevant to elucidating the mechanisms underlying skeletal muscle wasting observed in other chronic diseases, as well as in aging.

  2. The importance of tissue environment surrounding the tumor on the development of cancer cachexia.

    Science.gov (United States)

    Chiba, Fumihiro; Soda, Kuniyasu; Yamada, Shigeki; Tokutake, Yuka; Chohnan, Shigeru; Konishi, Fumio; Rikiyama, Toshiki

    2014-01-01

    The relationship between host factors and cancer cachexia was investigated. A single cell clone (clone 5 tumor) established from colon 26 adenocarcinoma by limiting dilution cell cloning methods was employed to eliminate the inoculation site-dependent differences in the composition of cell clones. Clone 5 tumor did not provoke manifestations of cancer cachexia when inoculated in subcutaneous tissue. However, when inoculated in the gastrocnemius muscle, the peritoneal cavity or the thoracic cavity of CD2F1 male mice, typical manifestations of cancer cachexia were observed in all groups of mice with intergroup variations. The blood levels of various cytokines, chemokines and hormones were increased but with wide intergroup variations. Analyses by stepwise multiple regression models revealed that serum interleukin-10 was the most significant factor associated with manifestations of cancer cachexia, suggesting the possible involvement of mechanisms similar to cancer patients suffering cancer cachexia. White blood cells, especially neutrophils, seemed to have some roles on the induction of cancer cachexia, because massive infiltrations and an increase in peripheral blood were observed in cachectic mice bearing clone 5 tumors. The amount of malonyl-CoA in liver correlated with manifestations of cancer cachexia, however the mRNA levels of spermidine/spermine N-1 acetyl transferase (SSAT) (of which overexpression has been shown to provoke manifestations similar to cancer cachexia) were not necessarily associated with cancer cachexia. These data suggest that the induction of cancer cachexia depends on the environment in which the tumor grows and that the infiltration of host immune cells into the tumor and the resultant increase in inflammation result in the production of cachectic factors, such as cytokines, leading to SSAT activation. Further, multiple factors likely mediate the mechanisms of cancer cachexia. Finally, this animal model was suitable for the investigation

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

    OpenAIRE

    2016-01-01

    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 ca...

  4. 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.

  5. 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.

  6. l-carnitine and cancer cachexia: Clinical and experimental aspects

    OpenAIRE

    Silvério, Renata; Laviano, Alessandro; Rossi Fanelli, Filippo; Seelaender, Marília

    2011-01-01

    Cancer cachexia is a multifaceted syndrome characterized, among many symptoms, by extensive muscle wasting. Chronic systemic inflammation, partly triggered and sustained by cytokines, as well as increased oxidative stress contributes to the pathogenesis of this complex metabolic disorder. l-carnitine plays a central role in the metabolism of fatty acids and shows important antioxidant and anti-inflammatory properties. Systemic carnitine depletion has been described in several diseases, and it...

  7. Cancer cachexia pathophysiology and translational aspect of herbal medicine.

    Science.gov (United States)

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

    2013-07-01

    About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Numerous cytokines have been postulated to play a role in the etiology of cancer cachexia. Cytokines can elicit effects that mimic leptin signaling and suppress orexigenic ghrelin and neuropeptide Y signaling, inducing sustained anorexia and cachexia not accompanied by the usual compensatory response. Furthermore, cytokines have been implicated in the induction of cancer-related muscle wasting. In particular, tumor necrosis factor-alpha, interleukin-1, interleukin-6 and interferon-gamma have been implicated in the induction of cancer-related muscle wasting. Cytokine-induced skeletal muscle wasting is probably a multifactorial process, which involves a depression in protein synthesis, an increase in protein degradation or a combination of both. Cancer patients suffer from the reduction in physical function, tolerance to anti-cancer therapy and survival, while many effective chemotherapeutic agents for cancer are burdened by toxicities that can reduce patient's quality of life or hinder their effective use. Herbal medicines have been widely used to help improve such conditions. Recent studies have shown that herbal medicines such as rikkunshito enhance ghrelin signaling and consequently improve nausea, appetite loss and cachexia associated with cancer or cancer chemotherapy, which worsens the quality of life and life expectancy of the patients. The multicomponent herbal medicines capable of targeting multiple sites could be useful for future drug discovery. Mechanistic studies and identification of active compounds could lead to new discoveries in biological and biomedical sciences.

  8. Malnutrition, cachexia and nutritional intervention: when much becomes too much

    Directory of Open Access Journals (Sweden)

    Serena Rianda

    2013-06-01

    Full Text Available Disease-associated malnutrition, also defined as cachexia, is a complex syndrome characterised by the progressive deterioration of nutritional status resulting from the combined effects of reduced appetite and food intake, and profound changes in host metabolism. Cachexia has been repeatedly demonstrated to represent a negative prognostic factor for patients suffering from acute and chronic diseases, including cancer. In oncology patients, early diagnosis of cachexia and timely nutritional intervention have been demonstrated not only to prevent further deterioration of nutritional status, but also to increase quality of life and survival when integrated in a multiprofessional and multidisciplinary approach. However, nutritional therapy is associated to the possible development of complications, which may be fatal. Therefore, nutritional therapy in severely malnourished patients should be cautiously prescribed by experts in the field, who should develop a monitoring program to early detect complications and to maximise the clinical efficacy.Here we describe a cancer patient affected by refeeding syndrome, who was fortunately early diagnosed and properly treated.

  9. The effectiveness of nutritional interventions in malnutrition and cachexia.

    Science.gov (United States)

    Baldwin, Christine

    2015-11-01

    Cancer is a common diagnosis and leading cause of death worldwide. Amounts of weight loss vary but it is associated with considerable morbidity, poorer quality of life and reduced survival. Nutritional intervention has the potential to maximise response to treatment and improve functioning and quality of life. The aim of this paper was to review the evidence for oral nutritional interventions in the management of weight loss in patients with cancer. Comparison of studies of nutritional support interventions in people with cancer is complicated by variations in understanding of what constitutes a compromised nutritional status. There are similarities and differences between definitions of both malnutrition and cachexia and studies of oral nutritional interventions have failed to use standard criteria at study inclusion contributing to heterogeneity amongst studies. Meta-analysis of randomised controlled trials has suggested limited evidence of benefit to nutritional and clinical outcomes but some improvements to aspects of quality of life. The presence of cachexia in patients with cancer might explain the limited efficacy of simple oral nutritional interventions, which lack a component designed to address metabolic abnormalities associated with cachexia. Novel strategies combining nutritional support with therapeutic agents designed to down-regulate the metabolic aberrations have failed to demonstrate consistent benefits and the results of multimodal treatments combining several interventions are awaited. There is a need for intervention studies recruiting patients early in the disease course, which underlines the need for definitions which predict poor outcome and hence allow early recognition of vulnerable patients.

  10. [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.

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

    Science.gov (United States)

    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.

  12. 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.

  13. Cancer anorexia-cachexia syndrome: psychological effect on the patient and family.

    Science.gov (United States)

    McClement, Susan

    2005-01-01

    The majority of patients with advanced cancer experience weight loss, reduced appetite, fatigue, and weakness. Chronic nausea and early satiety may also occur. This constellation of symptoms is known as the cancer anorexia-cachexia syndrome. Together with cancer pain, cancer anorexia-cachexia syndrome has been identified as 1 of the 2 most frequent and devastating problems affecting individuals with advanced malignancies. Research examining the issue of cancer anorexia-cachexia syndrome has been conducted; however, such work is largely biomedical in orientation. In contrast, the psychologic dimensions of the cancer anorexia-cachexia syndrome experience from the perspective of terminally ill patients and their family members is less well explored or described. The ability to provide psychosocial support to patients and families requires that caregivers appreciate the psychologic effect of cancer anorexia and cachexia on these individuals. This article examines that effect in light of existing knowledge and discusses the clinical implications arising from this work.

  14. Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival.

    Science.gov (United States)

    Johnston, Amelia J; Murphy, Kate T; Jenkinson, Laura; Laine, David; Emmrich, Kerstin; Faou, Pierre; Weston, Ross; Jayatilleke, Krishnath M; Schloegel, Jessie; Talbo, Gert; Casey, Joanne L; Levina, Vita; Wong, W Wei-Lynn; Dillon, Helen; Sahay, Tushar; Hoogenraad, Joan; Anderton, Holly; Hall, Cathrine; Schneider, Pascal; Tanzer, Maria; Foley, Michael; Scott, Andrew M; Gregorevic, Paul; Liu, Spring Yingchun; Burkly, Linda C; Lynch, Gordon S; Silke, John; Hoogenraad, Nicholas J

    2015-09-10

    The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tumors. We found that Fn14, when expressed in tumors, causes cachexia and that antibodies against Fn14 dramatically extended lifespan by inhibiting tumor-induced weight loss although having only moderate inhibitory effects on tumor growth. Anti-Fn14 antibodies prevented tumor-induced inflammation and loss of fat and muscle mass. Fn14 signaling in the tumor, rather than host, is responsible for inducing this cachexia because tumors in Fn14- and TWEAK-deficient hosts developed cachexia that was comparable to that of wild-type mice. These results extend the role of Fn14 in wound repair and muscle development to involvement in the etiology of cachexia and indicate that Fn14 antibodies may be a promising approach to treat cachexia, thereby extending lifespan and improving quality of life for cancer patients.

  15. 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

    2015-05-01

    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 and 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.

  16. 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

  17. 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

  18. Cancer as a Proinflammatory Environment: Metastasis and Cachexia

    Directory of Open Access Journals (Sweden)

    Nelson Inácio Pinto

    2015-01-01

    Full Text Available 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.

  19. Molecular characterization of skin microbiota between cancer cachexia patients and healthy volunteers.

    Science.gov (United States)

    Li, Wei; Han, Lei; Yu, Pengbo; Ma, Chaofeng; Wu, Xiaokang; Moore, John E; Xu, Jiru

    2014-04-01

    Systemic inflammation contributes to both the development of cancer and of cachexia. The microenvironment of bacterial habitats might be changed during the progression of cancer cachexia. The aim of this study was to quantitatively and qualitatively compare the composition of the skin microbiota between cancer cachexia patients and healthy volunteers. Cutaneous bacteria were swabbed at the axillary fossa of 70 cancer cachexia patients and 34 healthy individuals from China. Nested-PCR-denaturing gradient gel electrophoresis (PCR-DGGE) with primers specifically targeting V3 region and quantitative PCR (qPCR) for total bacteria, Corynebacterium spp., Staphylococcus spp., and Staphylococcus epidermidis were performed on all samples. Barcoded 454 pyrosequencing of the V3-V4 regions was performed on 30 randomly selected samples. By comparing diversity and richness indices, we found that the skin microbiome of cachectic cancer patients is less diverse than that of healthy participants, though these differences were not significant. The main microbes that reside on human skin were divided into four phyla: Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes. Staphylococcus spp. and Corynebacterium spp. were the dominant bacteria at the genus level. Significantly fewer Corynebacterium spp. had been observed in cachexia patients compared to healthy subjects. These results suggest that the presence of cancer and cachexia alters human skin bacterial communities. Understanding the changes in microbiota during cancer cachexia may lead to new insights into the syndrome.

  20. Identification of possible genetic polymorphisms involved in cancer cachexia: a systematic review

    Indian Academy of Sciences (India)

    Benjamin H. L. Tan; James A. Ross; Stein Kaasa; Frank Skorpen; Kenneth C. H. Fearon; European Palliative Care Research Collaborative

    2011-04-01

    Cancer cachexia is a polygenic and complex syndrome. Genetic variations in regulation of the inflammatory response, muscle and fat metabolic pathways, and pathways in appetite regulation are likely to contribute to the susceptibility or resistance to developing cancer cachexia. 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 clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Genes with variants which had functional or clinical associations with cachexia and replicated in at least one study were entered into pathway analysis software to reveal possible network associations between genes. A total of 184 polymorphisms with functional or clinical relevance to cancer cachexia were identified in 92 candidate genes. Of these, 42 polymorphisms (in 33 genes) were replicated in more than one study with 13 polymorphisms found to influence two or more hallmarks of cachexia (i.e. inflammation, loss of fat mass and/or lean mass and reduced survival). Thirty-three genes were found to be significantly interconnected in two major networks with four genes (ADIPOQ, IL6, NFKB1 and TLR4) interlinking both networks. Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides an initial framework to select genes/polymorphisms for further study in cancer cachexia, and to develop their potential as susceptibility biomarkers of developing cachexia.

  1. Review article: anorexia and cachexia in gastrointestinal cancer.

    Science.gov (United States)

    Ockenga, J; Valentini, L

    2005-10-01

    In patients with gastrointestinal malignancies, i.e. cancers of the stomach, colon, liver, biliary tract or pancreas, progressive undernutrition can be regularly observed during the course of illness. Undernutrition significantly affects the patients' quality of life, morbidity and survival. Pathogenetically, two different causes are relevant in the development of undernutrition in patients with gastrointestinal cancer. One cause is reduced nutritional intake. This condition is referred to as anorexia and can be worsened by the side effects of cancer therapy. The other cause is the release of endogenous transmitters and/or other products of the tumour leading to the cachexia syndrome, which is characterized by loss of body weight, negative nitrogen balance and fatigue. Cancer anorexia and cancer cachexia may have synergistic negative effects in affecting the patients' status. In this review, current nutritional support strategies with respect to different clinically relevant situations are described. An algorithm of the treatment strategies, including dietetic counselling, oral supplements, enteral and parenteral nutritional support is given. One focus is the approach of nutrition-focused patient care, which shows promising results. In addition, the possibilities of pharmacological intervention are discussed.

  2. Agmatine ameliorates adjuvant induced arthritis and inflammatory cachexia in rats.

    Science.gov (United States)

    Taksande, Brijesh G; Gawande, Dinesh Y; Chopde, Chandrabhan T; Umekar, Milind J; Kotagale, Nandkishor R

    2017-02-01

    The present study investigated the pharmacological effect of agmatine in Complete Freud Adjuvant (CFA) induced arthritis and cachexia in rats. The rats were injected with CFA (0.1ml/rat) to induced symptoms of arthritis. Day 8 onwards of CFA administration, rats were injected daily with agmatine for next 7days, and arthritis score, body weights and food intake were monitored daily (g). Since cachexia is known to produce severe inflammation, malnutrition and inhibition of albumin gene expression, we have also monitored the total proteins, albumin, TNF-α and IL-6 levels in arthritic rats and its modulation by agmatine. In the present study, CFA treated rats showed a progressive reduction in both food intake and body weight. In addition analysis of blood serum of arthritis animals showed a significant reduction in proteins and albumin and significant elevation in tumor necrosis factor (TNF)-α and Interleukins (IL)-6. Chronic agmatine (20-40mg/kg, ip) treatment not only attenuated the signs of arthritis but also reverses anorexia and body weight loss in CFA treated rats. In addition, agmatine restored total protein and albumin and reduces TNF-α and IL-6 levels in arthritis rats. These results suggest that agmatine administration can prevent the body weights loss and symptoms of arthritis via inhibition of inflammatory cytokines.

  3. Current and future care of patients with the cancer anorexia-cachexia syndrome.

    Science.gov (United States)

    Del Fabbro, Egidio

    2015-01-01

    Many important advances have occurred in the field of cancer cachexia over the past decade, including progress in understanding the mechanisms of the cancer anorexia-cachexia syndrome (CACS) and the development of promising pharmacologic and supportive care interventions. However, no approved agents for cancer cachexia currently exist, emphasizing the unmet need for an effective pharmacologic therapy. This article reviews the key elements of CACS assessment in daily practice, the contribution of nutritional impact symptoms (NIS), the evidence for current pharmacologic options, and promising anticachexia agents in perclinical and clinical trials. It also proposes a model for multimodality therapy and highlights issues pertinent to CACS in patients with pancreatic, gastric, and esophageal cancer.

  4. An Epidemiological Survey of Cachexia in Advanced Cancer Patients and Analysis on Its Diagnostic and Treatment Status.

    Science.gov (United States)

    Sun, Lei; Quan, Xiao-Qing; Yu, Shiying

    2015-01-01

    Recently, an international consensus diagnostic criterion for cancer cachexia was proposed. The aim of the study is to assess the prevalence of cachexia in patients with advanced cancer and to assess the current status of the diagnosis and management of cancer cachexia. A total of 390 patients with advanced cancer were included. There were 140 patients with cachexia and the prevalence was 35.9%. The prevalence was highest in pancreatic cancer (88.9%), followed by gastric cancer (76.5%) and esophageal cancer (52.9%). Sixty-three patients with cancer cachexia have CT scans available for muscle mass evaluation and 98.4% were sarcopenic. Cachectic patients have a significantly lower overall quality of life and a higher symptom burden. According to oncology physicians, only 33 patients were considered to have cancer cachexia. The false negative rate amounted to 76.4%. The positive rate was related to the body mass index and Eastern Cooperative Oncology Group performance status of the patients. There were few types of pharmacological approaches for cancer cachexia and more than half of cachectic patients did not receive any anticachexia treatment. These results indicate that the prevalence of cachexia in advanced cancer patients was high. However, cancer cachexia was rarely recognized and clinical management for cancer cachexia was very inadequate.

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

    NARCIS (Netherlands)

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

    2016-01-01

    Background & aims: 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.

  6. Knowledge and practice among dietitians in four Western European countries regarding malnutrition, starvation, cachexia and sarcopenia

    NARCIS (Netherlands)

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

    2015-01-01

    Adequate distinction between malnutrition, starvation, cachexia and sarcopenia is important in clinical care. Despite the overlap in physical characteristics, differences in etiology have therapeutical and prognostic implications. We aimed to determine whether dietitians in selected European countri

  7. Cancer cachexia update in head and neck cancer: Definitions and diagnostic features.

    Science.gov (United States)

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

    2015-04-01

    Cachexia is a profoundly debilitating wasting syndrome that affects patients with head and neck cancer and often contributes to their demise. A comprehensive literature search was performed up to April 2013 using PubMed, the Cochrane Library, CINAHL, and the Google search engine. For the meta-analyses, pooled prevalence estimates were calculated with a confidence interval of 95% (95% CI) by using random effects modeling. In this review, we outlined the unique challenges of cancer cachexia among patients with head and neck cancer by reviewing its impacts on quality of life (QOL), morbidity, and mortality. We explored the prevalence of different clinical markers of cachexia at the time of diagnosis and before and after treatment. Finally, we present updates regarding the diagnosis of cancer cachexia and recent findings, such as cardiac dysfunction that warrant clinical attention to more carefully identify patients at risk and potentially lead to better outcomes.

  8. 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.

  9. Refractory cachexia is associated with increased plasma concentrations of fentanyl in cancer patients

    Directory of Open Access Journals (Sweden)

    Suno M

    2015-05-01

    Full Text Available Manabu Suno,1,* Yuriko Endo,1,* Hiroyuki Nishie,2 Makoto Kajizono,3 Toshiaki Sendo,3 Junji Matsuoka4 1Department of Oncology Pharmaceutical Care and Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 3Department of Pharmacy, Okayama University Hospital, 4Faculty of Health Sciences, Okayama University Medical School, Okayama, Japan *These authors contributed equally to this work Background: An appropriate plasma concentration of fentanyl is the key to achieving good pain control in cancer patients. Cachexia, a multifactorial syndrome, is known to affect drug-metabolizing enzymes. However, the fentanyl concentrations in the blood of patients with cachexia have not been analyzed. The aim of this study was to evaluate the influence of cancer cachexia on dose-adjusted plasma fentanyl concentrations in cancer patients.Methods: Blood was collected from 21 Japanese cancer patients treated with a 24-hour transdermal fentanyl patch during the steady state of fentanyl plasma concentration. Plasma fentanyl concentrations were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS, and the levels were adjusted with the dose of fentanyl. Laboratory data were collected, and the cachexia stage was determined, based on study by Fearon et al. Multiple regression analysis was performed to identify the factors that affected fentanyl plasma concentrations.Results: Eight patients were classified as precachexia, nine as cachexia, and four as refractory cachexia, and the median dose-adjusted fentanyl concentrations (ng/mL per mg/kg/day were 27.5, 34.4, and 44.5, respectively. The dose-adjusted fentanyl concentration in patients with refractory cachexia was higher than that in patients with precachexia (Kruskal–Wallis test and post hoc Mann–Whitney U-test, P<0.01. The factors that

  10. Emerging Biomarkers in Heart Failure and Cardiac Cachexia

    Directory of Open Access Journals (Sweden)

    Goran Loncar

    2014-12-01

    Full Text Available Biomarkers are objective tools with an important role for diagnosis, prognosis and therapy optimization in patients with heart failure (HF. To date, natriuretic peptides are closest to optimal biomarker standards for clinical implications in HF. Therefore, the efforts to identify and test new biomarkers in HF are reasonable and justified. Along the natural history of HF, cardiac cachexia may develop, and once at this stage, patient performance and prognosis is particularly poor. For these reasons, numerous biomarkers reflecting hormonal, inflammatory and oxidative stress pathways have been investigated, but only a few convey relevant information. The complex pathophysiology of HF appears far too complex to be embraced by a single biomarker; thus, a combined approach appears reasonable. With these considerations, we have reviewed the recent developments in the field to highlight key candidates with diagnostic, prognostic and therapy optimization properties, either alone or in combination.

  11. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia.

    Science.gov (United States)

    Kir, Serkan; White, James P; Kleiner, Sandra; Kazak, Lawrence; Cohen, Paul; Baracos, Vickie E; Spiegelman, Bruce M

    2014-09-04

    Cachexia is a wasting disorder of adipose and skeletal muscle tissues that leads to profound weight loss and frailty. About half of all cancer patients suffer from cachexia, which impairs quality of life, limits cancer therapy and decreases survival. One key characteristic of cachexia is higher resting energy expenditure levels than in healthy individuals, which has been linked to greater thermogenesis by brown fat. How tumours induce brown fat activity is unknown. Here, using a Lewis lung carcinoma model of cancer cachexia, we show that tumour-derived parathyroid-hormone-related protein (PTHrP) has an important role in wasting, through driving the expression of genes involved in thermogenesis in adipose tissues. Neutralization of PTHrP in tumour-bearing mice blocked adipose tissue browning and the loss of muscle mass and strength. Our results demonstrate that PTHrP mediates energy wasting in fat tissues and contributes to the broader aspects of cancer cachexia. Thus, neutralization of PTHrP might hold promise for ameliorating cancer cachexia and improving patient survival.

  12. 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...

  13. [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.

  14. 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.

  15. Plasma Ghrelin Levels Are Associated with Anorexia but Not Cachexia in Patients with NSCLC

    Science.gov (United States)

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

    2017-01-01

    Background and Aims: The ghrelin receptor is one of the new therapeutic targets in the cancer anorexia-cachexia syndrome. Previous studies revealed that plasma ghrelin levels were high in patients with anorexia nervosa and low in obese subjects. We studied to what extent ghrelin levels are related with anorexia and cachexia in patients with cancer. Materials and Methods: Fasted ghrelin levels were determined as well as anorexia and cachexia in patients with stage III/IV non-small cell lung cancer before chemotherapy. Total plasma ghrelin was measured by radioimmunoassay. Anorexia was measured with the FAACT-A/CS questionnaire (cut-off value ≤ 37). Cachexia was determined as >5% weight loss (WL) in 6 months or >2% WL in 6 months in combination with low BMI or low muscle mass. The Kruskal-Wallis test was performed to assess differences in plasma ghrelin levels between four groups: patients with (+) or without (−) anorexia (A) or cachexia (C). Multiple regression analyses were performed to assess differences in plasma ghrelin levels between patients C+ and C− and patients with A+ and A− (adjusted for age and sex). Results: Forty patients with stage III (33%) or stage IV (68%) were recruited, of which 50% was male. Mean age was 59.6 ± 10.3 years. Sixteen patients had no anorexia or cachexia (A−C−), seven patients had both anorexia and cachexia (A+C+), ten patients had anorexia without cachexia (A+C−) and seven patients had cachexia without anorexia (A−C+). The levels of total plasma ghrelin were significantly different between the four groups of patients with or without anorexia or cachexia (p = 0.032): the A+C− patients had significantly higher ghrelin levels [median (IQR): 1,754 (1,404–2,142) compared to the A−C+ patients 1,026 (952–1,357), p = 0.003]. A+ patients had significantly higher ghrelin levels compared A− patients (C+ and C− combined, β: 304, p = 0.020). Plasma ghrelin levels were not significantly different in C+ patients

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies

    Indian Academy of Sciences (India)

    N. Johns; B. H. Tan; M. Macmillan; T. S. Solheim; J. A. Ross; V. E. Baracos; S. Damaraju; K. C. H. Fearon

    2014-12-01

    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 targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986–2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and

  18. Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies.

    Science.gov (United States)

    Johns, N; Tan, B H; MacMillan, M; Solheim, T S; Ross, J A; Baracos, V E; Damaraju, S; Fearon, K C H

    2014-12-01

    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 targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986-2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and

  19. 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

  20. 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.

  1. Rikkunshito Ameliorates Cancer Cachexia Partly through Elevation of Glucarate in Plasma

    Directory of Open Access Journals (Sweden)

    Katsuya Ohbuchi

    2015-01-01

    Full Text Available Cancer cachexia, which is characterized by decreased food intake, weight loss and systemic inflammation, increases patient’s morbidity and mortality. We previously showed that rikkunshito (RKT, a Japanese traditional herbal medicine (Kampo, ameliorated the symptoms of cancer cachexia through ghrelin signaling-dependent and independent pathways. To investigate other mechanisms of RKT action in cancer cachexia, we performed metabolome analysis of plasma in a rat model bearing the Yoshida AH-130 hepatoma. A total of 110 metabolites were detected in plasma and RKT treatment significantly altered levels of 23 of those metabolites in cachexia model rats. Among them, glucarate, which is known to have anticarcinogenic activity through detoxification of carcinogens via inhibition of β-glucuronidase, was increased in plasma following administration of RKT. In our AH-130 ascites-induced cachexia rat model, administration of glucarate delayed onset of weight loss, improved muscle atrophy, and reduced ascites content. Additionally, glucarate reduced levels of plasma interferon-γ (IFN-γ in tumor-bearing rats and was also found to suppress LPS-induced IFN-γ expression in splenocytes in vitro. These results suggest that glucarate has anti-inflammatory activity via a direct effect on immune host cells and suggest that RKT may also ameliorate inflammation partly through the elevation of glucarate in plasma.

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

    Science.gov (United States)

    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.

  3. β-Hydroxy-β-methylbutyrate as a countermeasure for cancer cachexia: a cellular and molecular rationale.

    Science.gov (United States)

    Kim, Jeong-Su; Khamoui, Andy V; Jo, Edward; Park, Bong-Sup; Lee, Won Jun

    2013-10-01

    Cancer cachexia is a life-threatening condition characterized by involuntary body weight loss and skeletal muscle wasting. In addition to being associated with poor prognosis and reduced survival, patients with cachexia exhibit a critical loss of physical function that impinges upon their ability to perform basic activities of daily living. Consequently, there is a loss of independence and a drastically reduced quality of life. Despite being a major unmet medical need of patients, very few treatment options exist. Maintaining muscle mass represents an important objective in the cancer patient trajectory not only because it relates to one's capacity to perform activities of daily living, but also because muscle preservation may be a critical determinant of survival while in a tumor-bearing state. In this regard, research has been directed towards identifying countermeasures effective in preserving muscle. With respect to nutritional approaches, administration of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) could be a viable component in multi-modal therapies targeting cancer cachexia. Evidence suggests that HMB treatment promotes regenerative events (i.e. myogenic program), suppresses protein degradation, and activates signaling pathways preceding protein synthesis and skeletal muscle growth. HMB therefore, could conceivably act on key regulatory events driving cancer cachexia, thereby favoring muscle growth/preservation. In this review, we take a mechanistic approach in making a case for the use of HMB provision as a possible therapeutic strategy for cancer cachexia by highlighting the cellular and molecular aspects of HMB function.

  4. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  7. Cachexia and sarcopenia: emerging syndromes of importance in dogs and cats.

    Science.gov (United States)

    Freeman, L M

    2012-01-01

    Cachexia is the loss of lean body mass (LBM) that affects a large proportion of dogs and cats with congestive heart failure (CHF), chronic kidney disease (CKD), cancer, and a variety of other chronic diseases. Sarcopenia, the loss of LBM that occurs with aging, is a related syndrome, although sarcopenia occurs in the absence of disease. As many of the diseases associated with muscle loss are more common in aging, cachexia and sarcopenia often are concurrent problems. Both cachexia and sarcopenia have important clinical implications because they are associated with increased morbidity and mortality. The pathophysiology of these 2 syndromes is complex and multifactorial, but recent studies have provided new information that has helped to clarify mechanisms and identify potential new targets for treatment. Newly identified mechanisms and pathways that mediate cachexia appear to act by increasing energy requirements, decreasing energy intake, impairing nutrient absorption, and causing metabolic alterations. Whereas cachexia and sarcopenia are important areas of research for drug development in people, they are only beginning to be recognized in veterinary medicine. Greater awareness and earlier diagnosis will help provide practical approaches to managing body weight and lean tissue in dogs and cats, as well as more directed targets for treatment.

  8. 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.

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

    Science.gov (United States)

    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.

  10. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia.

    Science.gov (United States)

    Petruzzelli, Michele; Schweiger, Martina; Schreiber, Renate; Campos-Olivas, Ramon; Tsoli, Maria; Allen, John; Swarbrick, Michael; Rose-John, Stefan; Rincon, Mercedes; Robertson, Graham; Zechner, Rudolf; Wagner, Erwin F

    2014-09-02

    Cancer-associated cachexia (CAC) is a wasting syndrome characterized by systemic inflammation, body weight loss, atrophy of white adipose tissue (WAT) and skeletal muscle. Limited therapeutic options are available and the underlying mechanisms are poorly defined. Here we show that a phenotypic switch from WAT to brown fat, a phenomenon termed WAT browning, takes place in the initial stages of CAC, before skeletal muscle atrophy. WAT browning is associated with increased expression of uncoupling protein 1 (UCP1), which uncouples mitochondrial respiration toward thermogenesis instead of ATP synthesis, leading to increased lipid mobilization and energy expenditure in cachectic mice. Chronic inflammation and the cytokine interleukin-6 increase UCP1 expression in WAT, and treatments that reduce inflammation or β-adrenergic blockade reduce WAT browning and ameliorate the severity of cachexia. Importantly, UCP1 staining is observed in WAT from CAC patients. Thus, inhibition of WAT browning represents a promising approach to ameliorate cachexia in cancer patients.

  11. MicroRNA in Cancer and Cachexia--A Mini-Review.

    Science.gov (United States)

    Acunzo, Mario; Croce, Carlo M

    2015-07-15

    MicroRNAs (miRNAs) are short noncoding RNAs with a length of approximately 22 nucleotides that are involved in posttranscriptional regulation of gene expression. miRNAs cover an important role in all biological processes, and aberrant miRNA expression is commonly associated with cancer. Recent discoveries have associated the involvement of miRNA in an increasingly large number of biological processes, including cachexia. The cachexia syndrome is a debilitating state of cancer that is, at least in part, associated with apoptosis. The mechanism through which tumors promote the characteristic distal loss of muscle and fat mass during the cachectic process is still not deeply investigated. In this review, we briefly describe the role of miRNAs in cancer development and cachexia.

  12. 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.

  13. 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...... and tissues mediated by cytokines, hormones and metabolites that are coupled with changes in body weight, composition and function as observed in obesity and cancer cachexia. In addition to established roles in intermediary metabolism, cell function and inflammation, organ-tissue crosstalk mediators...... are determinants of body composition and its change with weight gain and loss. The 12th Stock Conference supported Michael Stocks' concept of gaining new insights by integrating research ideas from obesity and cancer cachexia. The conference presentations provide an in-depth understanding of body composition...

  14. Regulation of hepatic cardiolipin metabolism by TNFα: Implication in cancer cachexia.

    Science.gov (United States)

    Peyta, Laure; Jarnouen, Kathleen; Pinault, Michelle; Coulouarn, Cedric; Guimaraes, Cyrille; Goupille, Caroline; de Barros, Jean-Paul Pais; Chevalier, Stephan; Dumas, Jean-François; Maillot, François; Hatch, Grant M; Loyer, Pascal; Servais, Stephane

    2015-11-01

    Cardiolipin (CL) content accumulation leads to an increase in energy wasting in liver mitochondria in a rat model of cancer cachexia in which tumor necrosis factor alpha (TNFα) is highly expressed. In this study we investigated the mechanisms involved in liver mitochondria CL accumulation in cancer cachexia and examined if TNFα was involved in this process leading to mitochondrial bioenergetics alterations. We studied gene, protein expression and activity of the main enzymes involved in CL metabolism in liver mitochondria from a rat model of cancer cachexia and in HepaRG hepatocyte-like cells exposed to 20 ng/ml of TNFα for 12 h. Phosphatidylglycerolphosphate synthase (PGPS) gene expression was increased 2.3-fold (pcachexia, TNFα induces a higher energy wasting in liver mitochondria by increasing CL content via upregulation of PGPS expression.

  15. Rheumatoid cachexia revisited: a metabolic co-morbidity in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kayo eMasuko

    2014-11-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease in which pro-inflammatory cytokines, including tumor necrosis factor (TNF-alpha, play a crucial role. The chronic inflammation, combined with reduced physical activity, leads to muscle wasting whereas fat mass would be maintained; the resulting abnormal metabolic state is described as rheumatoid cachexia. Since the loss of muscle volume would be compensated by the increased fat mass, body mass index (BMI is reported not to reflect the nutritional status in RA patients. The implication of rheumatoid cachexia for cardiovascular risk and clinical prognosis is not clearly understood, however, adequate control of disease activity in combination with appropriate physical exercise could be the most important strategy to control rheumatoid cachexia and related metabolic problems.

  16. 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

  17. Intervention of Mirtazapine on gemcitabine-induced mild cachexia in nude mice with pancreatic carcinoma xenografts

    Institute of Scientific and Technical Information of China (English)

    Shu-Man Jiang; Jian-Hua Wu; Lin Jia

    2012-01-01

    AIM:To investigate the effect of Mirtazapine on tumor growth,food intake,body weight,and nutritional status in gemcitabine-induced mild cachexia.METHODS:Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into Mirtazapine and control groups.Either Mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation.A model of mild cachexia was then established in both groups by intraperitoneal injection of Gemcitabine (50 mg/kg) 10 d,13 d,and 16 d after tumor implantation.Tumor size,food intake,body weight,and nutritional status were measured during the experiment.All mice were sacrificed at day 28.RESULTS:(1) After 7 d of gemcitabine administration,body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the Mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period,food intake and body weight were slightly greater for the Mirtazapine group compared with controls (although these differences were not statistically significant).After 21 d,mice in the Mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g,P =0.004).After 25 d,mice in the Mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g,P =0.014).CONCLUSION:Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice.Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice.It was believed to provide a potential therapeutic perspective for further studies on cachexia.

  18. 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.

  19. 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

    2016-09-01

    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 Apc(Min/+) 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.

  20. 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

  1. 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

  2. L-carnitine and cancer cachexia. I. L-carnitine distribution and metabolic disorders in cancer cachexia.

    Science.gov (United States)

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

    2012-07-01

    Cancer cachexia (CC), a progressive loss of body mass, is associated with decreased energy production. Abnormally low levels of L-carnitine (LC) in skeletal muscle means that mitochondrial β-oxidation of long-chain fatty acids (LCFA) does not occur efficiently in patients with CC. We assessed the influence of CC on LC distribution and the effects of parenteral lipid emulsions on plasma LC levels and urinary excretion. Fifty patients with CC were randomly assigned to total parenteral nutrition (TPN) with long-chain triglycerides (LCTs), or LCTs plus medium-chain triglycerides (MCTs) as 50/50. Patients were further separated into those with body-mass index (BMI) ≤ 19 kg/m(2) and BMI >19 kg/m(2). Plasma concentrations of total LC (TC) and free LC (FC) and their urinary excretion were measured, along with skeletal muscle LC levels. On average, plasma FC and TC were higher than reference values in all patients. Patients with BMI ≤ 19 kg/m(2) had lower plasma FC and TC than those with BMI >19 kg/m(2). Skeletal muscle FC in the BMI ≤ 19 kg/m(2) group was lower than reference value, but within the normal range in others. LC and FC urinary excretion was higher than reference values. Plasma LC and its urinary excretion were higher in patients administered pure LCTs relative to those given MCTs/LCTs. A decrease in skeletal muscle LC in cancer patients with CC (BMI ≤ 19 kg/m(2)) correlates with an increase in its plasma levels and increased renal excretion. A diet of MCTs/LCTs reduces LC release from muscle to plasma and urine more effectively than LCTs.

  3. Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Xiaodong Mu

    2016-01-01

    Full Text Available Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia.

  4. 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.

  5. Cancer cachexia: what is known about its etiology and what should be the current treatment approach?

    NARCIS (Netherlands)

    Halteren, H.K. van; Bongaerts, G.P.A.; Wagener, D.J.T.

    2003-01-01

    Cancer cachexia, defined as involuntary weight loss and tissue wasting due to cancer, negatively influences physical condition, quality of life and prognosis. Well known causes, such as ileus or hypercalcemia, do not suffice to explain the entire phenomenon. Metabolic changes induced by the tumor an

  6. Therapy insight: Cancer anorexia-cachexia syndrome--when all you can eat is yourself.

    Science.gov (United States)

    Laviano, Alessandro; Meguid, Michael M; Inui, Akio; Muscaritoli, Maurizio; Rossi-Fanelli, Filippo

    2005-03-01

    Tumor growth is associated with profound metabolic and neurochemical alterations, which can lead to the onset of anorexia-cachexia syndrome. Anorexia is defined as the loss of the desire to eat, while cachexia results from progressive wasting of skeletal muscle mass--and to a lesser extent adipose tissue--occurring even before weight loss becomes apparent. Cancer anorexia-cachexia syndrome is highly prevalent among cancer patients, has a large impact on morbidity and mortality, and impinges on patient quality of life. However, its clinical relevance is frequently overlooked, and treatments are usually only attempted during advanced stages of the disease. The pathogenic mechanisms of cachexia and anorexia are multifactorial, but cytokines and tumor-derived factors have a significant role, thereby representing a suitable therapeutic target. Energy expenditure in anorexia is frequently increased while energy intake is decreased, which further exacerbates the progressive deterioration of nutritional status. The optimal therapeutic approach to anorectic-cachectic cancer patients should be based on both changes in dietary habits, achieved via nutritional counseling; and drug therapy, aimed at interfering with cytokine expression or activity. Our improved understanding of the influence a tumor has on the host's metabolism is advancing new therapeutic approaches, which are likely to result in better preservation of nutritional status if started concurrently with specific antineoplastic treatment.

  7. Novel role for tumor-induced expansion of myeloid-derived cells in cancer cachexia.

    Science.gov (United States)

    Cuenca, Alex G; Cuenca, Angela L; Winfield, Robert D; Joiner, Dallas N; Gentile, Lori; Delano, Matthew J; Kelly-Scumpia, Kindra M; Scumpia, Philip O; Matheny, Michael K; Scarpace, Philip J; Vila, Lizette; Efron, Philip A; LaFace, Drake M; Moldawer, Lyle L

    2014-06-15

    Cancer progression is associated with inflammation, increased metabolic demand, infection, cachexia, and eventually death. Myeloid-derived suppressor cells (MDSCs) commonly expand during cancer and are associated with adaptive immune suppression and inflammatory metabolite production. We propose that cancer-induced cachexia is driven at least in part by the expansion of MDSCs. MDSC expansion in 4T1 mammary carcinoma-bearing hosts is associated with induction of a hepatic acute-phase protein response and altered host energy and fat metabolism, and eventually reduced survival to polymicrobial sepsis and endotoxemia. Similar results are also seen in mice bearing a Lewis lung carcinoma and a C26 colon adenocarcinoma. However, a similar cachexia response is not seen with equivalent growth of the 66C4 subclone of 4T1, in which MDSC expansion does not occur. Importantly, reducing MDSC numbers in 4T1-bearing animals can ameliorate some of these late responses and reduce susceptibility to inflammation-induced organ injury and death. In addition, administering MDSCs from both tumor- and nontumor-bearing mice can produce an acute-phase response. Thus, we propose a previously undescribed mechanism for the development of cancer cachexia, whereby progressive MDSC expansion contributes to changes in host protein and energy metabolism and reduced resistance to infection.

  8. Cancer cachexia demonstrates the energetic impact of gluconeogenesis in human metabolism.

    NARCIS (Netherlands)

    Bongaerts, G.P.A.; Halteren, H.K. van; Verhagen, C.A.H.H.V.; Wagener, D.J.T.

    2006-01-01

    A review-based hypothesis is presented on the energy flow in cancer patients. This hypothesis centres on the hypoxic condition of tumours, the essential metabolic consequences, especially the gluconeogenesis, the adaptation of the body, and the pathogenesis of cancer cachexia. In growing tumours the

  9. AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients.

    Science.gov (United States)

    Avan, Abolfazl; Avan, Amir; Le Large, Tessa Y S; Mambrini, Andrea; Funel, Niccola; Maftouh, Mina; Ghayour-Mobarhan, Majid; Cantore, Maurizio; Boggi, Ugo; Peters, Godefridus J; Pacetti, Paola; Giovannetti, Elisa

    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.

  10. Central nervous system mechanisms contributing to the cachexia-anorexia syndrome.

    Science.gov (United States)

    Plata-Salamán, C R

    2000-10-01

    The cachexia-anorexia syndrome occurs in chronic pathophysiologic processes including cancer, infection with human immunodeficiency virus, bacterial and parasitic diseases, inflammatory bowel disease, liver disease, obstructive pulmonary disease, cardiovascular disease, and rheumatoid arthritis. Cachexia makes an organism susceptible to secondary pathologies and can result in death. Cachexia-anorexia may result from pain, depression or anxiety, hypogeusia and hyposmia, taste and food aversions, chronic nausea, vomiting, early satiety, malfunction of the gastrointestinal system (delayed digestion, malabsorption, gastric stasis and associated delayed emptying, and/or atrophic changes of the mucosa), metabolic shifts, cytokine action, production of substances by tumor cells, and/or iatrogenic causes such as chemotherapy and radiotherapy. The cachexia-anorexia syndrome also involves metabolic and immune changes (mediated by either the pathophysiologic process, i.e., tumor, or host-derived chemical factors, e.g., peptides, neurotransmitters, cytokines, and lipid-mobilizing factors) and is associated with hypertriacylglycerolemia, lipolysis, and acceleration of protein turnover. These changes result in the loss of fat mass and body protein. Increased resting energy expenditure in weight-losing cachectic patients can occur despite the reduced dietary intake, indicating a systemic dysregulation of host metabolism. During cachexia, the organism is maintained in a constant negative energy balance. This can rarely be explained by the actual energy and substrate demands by tumors in patients with cancer. Overall, the cachectic profile is significantly different than that observed during starvation. Cachexia may result not only from anorexia and a decreased caloric intake but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions). In any case, the major deficit of a cachectic organism is a negative energy balance. Cytokines are proposed to participate

  11. 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.

  12. 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

    2011-07-26

    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.

  13. [Feeding-related disorders in medicine, with special reference to cancer anorexia-cachexia syndrome].

    Science.gov (United States)

    Inui, Akio

    2006-10-01

    Cachexia is among the most debilitating and life-threatening aspects of cancer. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process results from a failure of the adaptive feeding response seen in simple starvation and includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin, a hormone secreted by adipose tissue, which is an integral component of the homeostatic loop of body weight regulation. The two major options for pharmacological therapy have been either progestational agents or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome continues to lead to effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide, all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. The outcomes of drug studies in cancer cachexia should focus on the symptomatic and quality-of-life advantages rather than simply on nutritional end points, since the survival of cachexia cancer patients may be limited to weeks or months due to the incurable nature of the underlying malignancy. As weight loss shortens the survival time of cancer patients and decreases their performance status, effective therapy would extend patient survival and improve quality of life.

  14. 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.

  15. 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.

  16. 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.

  17. Inhibition of the renin-angiotensin system improves physiological outcomes in mice with mild or severe cancer cachexia.

    Science.gov (United States)

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

    2013-09-01

    Cancer cachexia describes the progressive skeletal muscle wasting and weakness associated with many cancers. Cachexia reduces mobility and quality of life and accounts for 20-30% of all cancer-related deaths. Activation of the renin-angiotensin system causes skeletal muscle wasting and weakness. We tested the hypothesis that treatment with the angiotensin converting enzyme (ACE) inhibitor, perindopril, would enhance whole body and skeletal muscle function in cachectic mice bearing Colon-26 (C-26) tumors. CD2F1 mice received a subcutaneous injection of phosphate buffered saline or C-26 tumor cells inducing either a mild or severe cachexia. The following day, one cohort of C-26 mice began receiving perindopril in their drinking water (4 mg kg(-1) day(-1) ) for 21 days. In mild and severe cachexia, perindopril increased measures of whole body function (grip strength and rotarod) and reduced fatigue in isolated contracting diaphragm muscle strips (p cancer cachexia and should be confirmed in future clinical trials. Since ACE inhibition alone did not enhance body or muscle mass, co-treatment with an anabolic agent may be required to address these aspects of cancer cachexia.

  18. MicroRNA profiling links miR-378 to enhanced adipocyte lipolysis in human cancer cachexia.

    Science.gov (United States)

    Kulyté, Agné; Lorente-Cebrián, Silvia; Gao, Hui; Mejhert, Niklas; Agustsson, Thorhallur; Arner, Peter; Rydén, Mikael; Dahlman, Ingrid

    2014-02-01

    Cancer cachexia is associated with pronounced adipose tissue loss due to, at least in part, increased fat cell lipolysis. MicroRNAs (miRNAs) have recently been implicated in controlling several aspects of adipocyte function. To gain insight into the possible impact of miRNAs on adipose lipolysis in cancer cachexia, global miRNA expression was explored in abdominal subcutaneous adipose tissue from gastrointestinal cancer patients with (n = 10) or without (n = 11) cachexia. Effects of miRNA overexpression or inhibition on lipolysis were determined in human in vitro differentiated adipocytes. Out of 116 miRNAs present in adipose tissue, five displayed distinct cachexia-associated expression according to both microarray and RT-qPCR. Four (miR-483-5p/-23a/-744/-99b) were downregulated, whereas one (miR-378) was significantly upregulated in cachexia. Adipose expression of miR-378 associated strongly and positively with catecholamine-stimulated lipolysis in adipocytes. This correlation is most probably causal because overexpression of miR-378 in human adipocytes increased catecholamine-stimulated lipolysis. In addition, inhibition of miR-378 expression attenuated stimulated lipolysis and reduced the expression of LIPE, PLIN1, and PNPLA2, a set of genes encoding key lipolytic regulators. Taken together, increased miR-378 expression could play an etiological role in cancer cachexia-associated adipose tissue loss via effects on adipocyte lipolysis.

  19. Comparing two classifications of cancer cachexia and their association with survival in patients with unresected pancreatic cancer.

    Science.gov (United States)

    Wesseltoft-Rao, Nima; Hjermstad, Marianne J; Ikdahl, Tone; Dajani, Olav; Ulven, Stine M; Iversen, Per Ole; Bye, Asta

    2015-01-01

    There is no universally accepted definition of cancer cachexia. Two classifications have been proposed; the 3-factor classification requiring ≥ 2 of 3 factors; weight loss ≥ 10%, food intake ≤ 1500 kcal/day, and C-reactive protein ≥ 10 mg/l, and the consensus classification requiring weight loss >5% the past 6 mo, or body mass index 2%. Precachexia is the initial stage of the cachexia trajectory, identified by weight loss ≤ 5%, anorexia and metabolic change. We examined the consistency between the 2 classifications, and their association with survival in a palliative cohort of 45 (25 men, median age of 72 yr, range 35-89) unresected pancreatic cancer patients. Computed tomography images were used to determine sarcopenia. Height/weight/C-reactive protein and survival were extracted from medical records. Food intake was self-reported. The agreement for cachexia and noncachexia was 78% across classifications. Survival was poorer in cachexia compared to noncachexia (3-factor classification, P = 0.0052; consensus classification, P = 0.056; when precachexia was included in the consensus classification, P = 0.027). Both classifications showed a trend toward lower median survival (P cachexia. In conclusion, the two classifications showed good overall agreement in defining cachectic pancreatic cancer patients, and cachexia was associated with poorer survival according to both.

  20. Role of NF-κB and cytokine in experimental cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    Wei Zhou; Zhi-Wei Jiang; Jie Tian; Jun Jiang; Ning Li; Jie-Shou Li

    2003-01-01

    AIM: To assess the putative involvement of NF-κB and proinflammatory cytokines in the pathogenesis of cancer cachexia and the therapeutic efficacy of indomethacin (IND)on cachexia.METHODS: Thirty young male BABL/c mice were divided randomly into five groups: (a) control, (b) tumor-bearing murine were inoculated subcutaneously to induce cachexia.Saline and IND were given intraperitoneally daily for 7 days from the onset of cachexia to sacrifice. Food intake and body composition were documented, serum levels of TNFα and IL-6 and activity of NF-κB in the spleen were investigated in all animals.RESULTS: Weight loss was observed in all tumor-bearing mice. By day 16, body weights of non-tumor mice were about 72 % of healthy controls (P<0.01), and the weight of gastrocnemius was decreased by 28.7 % (P<0.01). No difference was found between groups in food intake (P>0.05).Gastrocnemius weight was increased markedly (P<0.01)body weights were not significantly elevated. Tumor-bearing caused a 2-3 fold increase in serum levels of both TNF-αand IL-6 (P<0.01). The concentration of TNF-α (P<0.05)and IL-6 (P<0.01) in tumor-bearing mice was reduced after of IL-6 was slightly elevated following treatment of IND 2.0tumor-bearing mice in comparison with controls in electrophoretic mobility shift assay (ENSA). NF-κB activity a higher NF-κB activity was observed in mice treated with CONCLUSION: Colon 26 adenocarcinoma cells can induce severe cancer cachexia experimentally, and the mechanism may be partially due to the enhanced TNF-αand IL-6 in tumor-bearing animals, which is controlled by NF-κB. Low dose of indomethacin alleviates the cachexia,decreases the activation of NF-κB and the serum levels of TNF-α and IL-6, and prevents body weight loss and muscle atrophy, while no further effect is gained by a higher dosage.

  1. 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.

  2. Effect of Feeding Status on Adjuvant Arthritis Severity, Cachexia, and Insulin Sensitivity in Male Lewis Rats

    Directory of Open Access Journals (Sweden)

    Andrea Stofkova

    2010-01-01

    Full Text Available We studied the effect of food restriction, overfeeding, and normofeeding on cachexia, inflammatory and metabolic parameters, and insulin sensitivity in chronic adjuvant arthritis (AA in rats. Food restriction during AA increased circulating ghrelin, corticosterone, decreased leptin, and ameliorated arthrogram score and systemic inflammation compared to normofeeding. Overfeeding worsened arthrogram score and systemic inflammation, and led to lipid accumulation in the liver, but not to alterations of adipokine and ghrelin plasma levels relative to normofeeding. Independently of feeding status, AA induced cachexia, in which modulation of mRNA expressions for appetite-regulating neuropeptides (NPY, AgRP, POMC, CART in the arcuate nucleus (ARC does not play a primary role. The overexpression of IL-1β mRNA in the ARC suggests its role in the mechanisms of impaired energy balance during AA under all feeding conditions. Normal HOMA index in all arthritic groups does not indicate the development of insulin resistance by feeding interventions in these rats.

  3. 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.

  4. 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.

  5. Anamorelin hydrochloride in the treatment of cancer anorexia-cachexia syndrome.

    Science.gov (United States)

    Currow, David C; Abernethy, Amy P

    2014-04-01

    Anamorelin hydrochloride is an orally active ghrelin receptor agonist in development by Helsinn, for the treatment of non-small-cell lung cancer (NSCLC) cachexia. In preclinical and clinical studies, the potent affinity of anamorelin for the ghrelin receptor is associated with significant appetite-enhancing activity and resultant improvements in body weight, lean body mass, and handgrip strength compared with placebo. The accompanying stimulatory effects on growth hormone and IGF-1 are not associated with tumor growth, and overall survival in patients with cancer is not compromised. Anamorelin is well tolerated with no dose-limiting toxicities identified to date. The findings of ongoing Phase III studies are needed to confirm the significant potential of anamorelin to treat NSCLC cachexia.

  6. 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.

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

    Science.gov (United States)

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

    2015-01-01

    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. PMID:26092726

  8. 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.

  9. Rikkunshito ameliorates cachexia associated with bleomycin-induced lung fibrosis in mice by stimulating ghrelin secretion.

    Science.gov (United States)

    Tsubouchi, Hironobu; Yanagi, Shigehisa; Miura, Ayako; Mogami, Sachiko; Yamada, Chihiro; Iizuka, Seiichi; Hattori, Tomohisa; Nakazato, Masamitsu

    2014-10-01

    Cachexia is a frequent complication in patients with respiratory failure, such as lung fibrosis, and it is a determining factor for functional capacity, health status, and mortality. Reductions in body weight and skeletal muscle mass are key features of cachexia that are resistant to current therapies. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment for patients with gastrointestinal symptoms and known to stimulate ghrelin secretion. By using bleomycin (BLM)-induced lung fibrosis mice in this study, we tested our hypothesis that RKT administration could ameliorate pulmonary cachexia. After BLM administration, mice were provided with either RKT or distilled water on a daily basis. Compared with the BLM-injected mice, the RKT-treated mice had smaller reductions of food intake and body weight. Skeletal muscle weights were retained in the RKT-treated mice, in conjunction with reduced expressions of MuRF-1 and atrogin-1 in the lysates of skeletal muscle found in lung fibrosis. Rikkunshito administration restored the plasma concentrations of ghrelin in BLM-injected mice. The anticachectic efficacies of RKT administration in BLM-injected mice were canceled by the concurrent treatment of a ghrelin receptor antagonist. Rikkunshito administration did not decrease the degree of loss of body weight or food intake reduction in either ghrelin-deficient mice or growth hormone secretagogue receptor-deficient mice. Our results indicate that RKT administration exerts protective effects on pulmonary cachexia by ameliorating skeletal muscle wasting and food intake reduction as mediated by the ghrelin system and, thus, highlight RKT as a potential therapeutic agent for the management of lung fibrosis.

  10. Cardiac and skeletal muscles show molecularly distinct responses to cancer cachexia.

    Science.gov (United States)

    Shum, Angie M Y; Fung, David C Y; Corley, Susan M; McGill, Max C; Bentley, Nicholas L; Tan, Timothy C; Wilkins, Marc R; Polly, Patsie

    2015-12-01

    Cancer cachexia is a systemic, paraneoplastic syndrome seen in patients with advanced cancer. There is growing interest in the altered muscle pathophysiology experienced by cachectic patients. This study reports the microarray analysis of gene expression in cardiac and skeletal muscle in the colon 26 (C26) carcinoma mouse model of cancer cachexia. A total of 268 genes were found to be differentially expressed in cardiac muscle tissue, compared with nontumor-bearing controls. This was fewer than the 1,533 genes that changed in cachectic skeletal muscle. In addition to different numbers of genes changing, different cellular functions were seen to change in each tissue. The cachectic heart showed signs of inflammation, similar to cachectic skeletal muscle, but did not show the upregulation of ubiquitin-dependent protein catabolic processes or downregulation of genes involved in cellular energetics and muscle regeneration that characterizes skeletal muscle cachexia. Quantitative PCR was used to investigate a subset of inflammatory genes in the cardiac and skeletal muscle of independent cachectic samples; this revealed that B4galt1, C1s, Serpina3n, and Vsig4 were significantly upregulated in cardiac tissue, whereas C1s and Serpina3n were significantly upregulated in skeletal tissue. Our skeletal muscle microarray results were also compared with those from three published microarray studies and found to be consistent in terms of the genes differentially expressed and the functional processes affected. Our study highlights that skeletal and cardiac muscles are affected differently in the C26 mouse model of cachexia and that therapeutic strategies cannot assume that both muscle types will show a similar response.

  11. 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.

  12. Management of Anorexia-Cachexia in Late Stage Lung Cancer Patients.

    Science.gov (United States)

    Del Ferraro, Catherine; Grant, Marcia; Koczywas, Marianna; Dorr-Uyemura, Laura A

    2012-08-01

    Nutritional deficiencies are experienced by most adults with advanced lung cancer during the course of their disease and treatment. Well-nourished individuals tolerate cancer treatment with less morbidity, mortality, and increased response to treatment as compared to those who are malnourished. Novel anti-cancer therapies cause many deficits that impact nutritional and functional status during the treatment process. Nutritional deficits include weight loss, malnutrition, and anorexia-cachexia. Anorexia-Cachexia is complex, not well understood and seen in many solid tumors in late stage disease. Assessing adequate nutrition is one of the most challenging problems for nurses, their patients and patient's families. The purpose of this review is to define and describe cancer anorexia-cachexia in late stage lung cancer, through case presentation, and to describe palliative strategies for prevention, assessment, and management in the palliative care setting. Early assessment for nutritional imbalances must be done regularly with re-evaluation for intervention effectiveness and should continue throughout the illness trajectory. Management of adverse effects of cancer and cancer-related treatment is critical to improving quality of life. Palliative care and hospice nurses play a critical role in early assessment, education and prevention to support nutritional needs for patients and their families.

  13. Tumor inoculation site affects the development of cancer cachexia and muscle wasting.

    Science.gov (United States)

    Matsuyama, Tatsuzo; Ishikawa, Takeshi; Okayama, Tetsuya; Oka, Kaname; Adachi, Satoko; Mizushima, Katsura; Kimura, Reiko; Okajima, Manabu; Sakai, Hiromi; Sakamoto, Naoyuki; Katada, Kazuhiro; Kamada, Kazuhiro; Uchiyama, Kazuhiko; Handa, Osamu; Takagi, Tomohisa; Kokura, Satoshi; Naito, Yuji; Itoh, Yoshito

    2015-12-01

    The phenotype and severity of cancer cachexia differ among tumor types and metastatic site in individual patients. In this study, we evaluated if differences in tumor microenvironment would affect the development of cancer cachexia in a murine model, and demonstrated that body weight, adipose tissue and gastrocnemius muscle decreased in tumor-bearing mice. Interestingly, a reduction in heart weight was observed in the intraperitoneal tumor group but not in the subcutaneous group. We evaluated 23 circulating cytokines and members of the TGF-β family, and found that levels of IL-6, TNF-α and activin A increased in both groups of tumor-bearing mice. Eotaxin and G-CSF levels in the intraperitoneal tumor group were higher than in the subcutaneous group. Atrogin 1 and MuRF1 mRNA expressions in the gastrocnemius muscle increased significantly in both groups of tumor-bearing mice, however, in the myocardium, expression of these mRNAs increased in the intraperitoneal group but not in subcutaneous group. Based on these results, we believe that differences in microenvironment where tumor cells develop can affect the progression and phenotype of cancer cachexia through alterations in various circulating factors derived from the tumor microenvironment.

  14. Combined approach to counteract experimental cancer cachexia: eicosapentaenoic acid and training exercise.

    Science.gov (United States)

    Penna, Fabio; Busquets, Silvia; Pin, Fabrizio; Toledo, Miriam; Baccino, Francesco M; López-Soriano, Francisco J; Costelli, Paola; Argilés, Josep M

    2011-06-01

    BACKGROUND: Cancer cachexia is a syndrome characterized by loss of skeletal muscle protein, depletion of lipid stores, anorexia, weakness, and perturbations of the hormonal homeostasis. Despite several therapeutic approaches described in the past, effective interventions countering cancer cachexia are still lacking. METHODS: The present work was aimed to verify the ability of eicosapentaenoic acid (EPA) to prevent the muscle depletion in Lewis lung carcinoma-bearing mice and to test the ability of endurance exercise training to increase the EPA effect. RESULTS: EPA alone did not prevent the muscle loss induced by tumor growth while the combination with exercise induced a partial rescue of muscle strength and mass. Moreover, the association of EPA and exercise reduced the dramatic PAX-7 accumulation and stimulated the increase of PCG-1 protein. CONCLUSIONS: Overall, the present data suggest that exercise is an effective tool that should be added for combined therapeutic approaches against cancer cachexia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13539-011-0028-4) contains supplementary material, which is available to authorized users.

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

    Science.gov (United States)

    Kim, Eun Young; Kim, Young Saing; Seo, Ja-Young; Park, Inkeun; Ahn, Hee Kyung; Jeong, Yu Mi; Kim, Jeong Ho; Kim, Nambeom

    2016-01-01

    Background 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. Objective To determine the relationship between systemic inflammatory markers and CT-determined muscle mass in patients with SCLC. Methods 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 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 cancer cachexia. PMID:27537502

  16. Anorexia and cachexia in prostaglandin EP1 and EP3 subtype receptor knockout mice bearing a tumor with high intrinsic PGE2 production and prostaglandin related cachexia.

    Science.gov (United States)

    Wang, W; Andersson, M; Lönnroth, C; Svanberg, E; Lundholm, K

    2005-03-01

    Previous studies in our laboratory have suggested that prostaglandin (PG) E2 is involved in anorexia/cachexia development in MCG 101 tumor-bearing mice. However, the role of COX pathways in the pathogenesis of cancer anorexia/cachexia is not fully resolved. In the present study, we investigated the role of PGE receptors subtype EP1 and EP3 on the development of anorexia in MCG 101-bearing mice. Our results show that the absence of host EP1 or EP3 receptors did not alter the magnitude of anorexia in tumor-bearers. However, anorexia in tumor-bearing EP1 and EP3 knockouts was not improved by indomethacin treatment as observed in wild type tumor-bearers. By contrast, indomethacin improved body composition similar in EP1 and EP3 knockouts as well as in wild type tumor-bearing animals and tumor growth was retarded in EP1 and promoted in EP3 knock outs. Our results demonstrate that host EP1 and EP3 receptors are involved in the control of local tumor growth, which translates into anorexia, this being the main cause of metabolic adaptive alterations to explain weight loss in this model. Brain EP1 and EP3 subtype receptors do not seem to directly control anorexia, which leaves EP2 and EP4 as potential candidates.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  19. Towards a simple objective framework for the investigation and treatment of cancer cachexia: the Glasgow Prognostic Score.

    Science.gov (United States)

    Douglas, Euan; McMillan, Donald C

    2014-07-01

    Progress in the treatment of progressive involuntary weight loss in patients with cancer (cancer cachexia) remains dismally slow. Cancer cachexia and its associated clinical symptoms, including weight loss, altered body composition, poor functional status, poor food intake, and poorer quality of life, have long been recognised as indicators of poorer prognosis in the patient with cancer. In order to make some progress a starting point is to have general agreement on what constitutes cancer cachexia. In recent years a plethora of different definitions and consensus statements have been proposed as a framework for investigation and treatment of this debilitating and terminal condition. However, there are significant differences in the criteria used in these and all include poorly defined or subjective criteria and their prognostic value has not been established. The aim of the present review was to examine the hypothesis that a systemic inflammatory response accounts for most of the effect of cancer cachexia and its associated clinical symptoms on poor outcome in patients with cancer. Furthermore, to put forward the case for the Glasgow Prognostic Score to act a simple objective framework for the investigation and treatment of cancer cachexia.

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

    Science.gov (United States)

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

    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 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.

  1. Validation of the CAchexia SCOre (CASCO). Staging Cancer Patients: The Use of miniCASCO as a Simplified Tool

    Science.gov (United States)

    Argilés, Josep M.; Betancourt, Angelica; Guàrdia-Olmos, Joan; Peró-Cebollero, Maribel; López-Soriano, Francisco J.; Madeddu, Clelia; Serpe, Roberto; Busquets, Sílvia

    2017-01-01

    The CAchexia SCOre (CASCO) was described as a tool for the staging of cachectic cancer patients. The aim of this study is to show the metric properties of CASCO in order to classify cachectic cancer patients into three different groups, which are associated with a numerical scoring. The final aim was to clinically validate CASCO for its use in the classification of cachectic cancer patients in clinical practice. We carried out a case -control study that enrolled prospectively 186 cancer patients and 95 age-matched controls. The score includes five components: (1) body weight loss and composition, (2) inflammation/metabolic disturbances/immunosuppression, (3) physical performance, (4) anorexia, and (5) quality of life. The present study provides clinical validation for the use of the score. In order to show the metric properties of CASCO, three different groups of cachectic cancer patients were established according to the results obtained with the statistical approach used: mild cachexia (15 ≤ × ≤ 28), moderate cachexia (29 ≤ × ≤ 46), and severe cachexia (47 ≤ × ≤ 100). In addition, a simplified version of CASCO, MiniCASCO (MCASCO), was also presented and it contributes as a valid and easy-to-use tool for cachexia staging. Significant statistically correlations were found between CASCO and other validated indexes such as Eastern Cooperative Oncology Group (ECOG) and the subjective diagnosis of cachexia by specialized oncologists. A very significant estimated correlation between CASCO and MCASCO was found that suggests that MCASCO might constitute an easy and valid tool for the staging of the cachectic cancer patients. CASCO and MCASCO provide a new tool for the quantitative staging of cachectic cancer patients with a clear advantage over previous classifications. PMID:28261113

  2. [Recent development in research and management of cancer anorexia-cachexia syndrome].

    Science.gov (United States)

    Inui, Akio

    2005-06-01

    Cachexia is among the most debilitating and life-threatening aspects of cancer, and is more common in children and elderly patients. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process results from a failure of the adaptive feeding response seen in simple starvation and includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin, a hormone secreted by adipose tissue, which is an integral component of the homeostatic loop of body weight regulation. This could be done by persistent inhibition of feeding-stimulatory circuitry including neuropeptide Y. Cachexia should be suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a 3-6-month period. The two major options for pharmacological therapy have been either progestational agents or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide-all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. The outcomes of drug studies in cancer cachexia should focus on the symptomatic and quality-of-life advantages rather than simply on nutritional end points, since the survival of cachexia cancer patients may be limited to weeks or months due to the incurable nature of the

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Laviano, Alessandro

    2016-01-01

    Abstract 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. PMID:27625919

  5. Ghrelin relieves cancer cachexia associated with the development of lung adenocarcinoma in mice.

    Science.gov (United States)

    Tsubouchi, Hironobu; Yanagi, Shigehisa; Miura, Ayako; Matsumoto, Nobuhiro; Kangawa, Kenji; Nakazato, Masamitsu

    2014-11-15

    Cancer cachexia is a multifactorial, critical illness syndrome characterized by an ongoing loss of skeletal muscle and adipose tissue. The reductions in body weight and skeletal muscle mass are important prognostic indicators for cancer patients that are refractory to current therapies. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is produced in the stomach, stimulates food intake and growth hormone secretion, suppresses inflammation, and prevents muscle catabolism. We investigated the pharmacological potential of ghrelin in the treatment of cancer cachexia by using urethane-treated, bronchioalveolar epithelium-specific Pten-deficient mice that developed lung adenocarcinomas. Ghrelin or phosphate-buffered saline was given to mice daily for four weeks beginning at five months after urethane injection, which corresponded to the time point of lung adenocarcinoma formation. Ghrelin inhibited the inductions of C-reactive protein, tumor necrosis factor-α, interleukin-1β, and interleukin-6, mitigated the reduction of food intake and fat mass, and consequently ameliorated body weight loss in the mouse model of lung adenocarcinoma. We also demonstrated that skeletal muscle mass and muscle contraction force in both fast-twitch muscle and slow-twitch muscle were retained in ghrelin-treated mice in conjunction with an upregulation of local insulin-like growth factor 1/Akt signaling. In addition, ghrelin administration reduced the expressions of phosphorylated-p38 mitogen-activated protein kinase, phosphorylated-nuclear factor-kappa B, Forkhead box protein O1, muscle RING-finger protein-1, and F-Box protein 32 in the lysates of skeletal muscle in the tumor-bearing state. Our results indicate that ghrelin administration exerts a protective effect against cancer cachexia by ameliorating skeletal muscle wasting and regulating systemic inflammation.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. Positive Prehabilitative Effect of Intense Treadmill Exercise for Ameliorating Cancer Cachexia Symptoms in a Mouse Model

    Science.gov (United States)

    Jee, Hyunseok; Chang, Ji-Eun; Yang, Eun Joo

    2016-01-01

    Due to the importance of exercise in prehabilitation, we conducted this study to understand the effects of different exercise intensities on cancer-related cachexia. Forty adult male CDF1 mice were randomly divided into a non-cancer control group (N=10, NC), cancer control group (N=10, CC), cancer with moderate exercise group (N=10, ME, 70% maxHR), and cancer with intense exercise group (N=10, SE, 90% maxHR) for obtaining data such as tissue weight and body weight changes, quality of life (QoL) indicators, and levels of cytokines and a muscle homeostasis regulatory protein. We verified that mouse colonic carcinoma cancer cells metastasized based on our observation that the weight of CC group lungs was almost 87% greater than NC group lungs. Survival rates of SE, NC, ME, and CC groups were 100%, 100%, 80%, and 50%, respectively (p<0.01). Other results such as tissue and body weight changes, QoL indicators, and protein analyses also supported our hypothesis that the SE group had improved survival compared to CC and ME groups (p<0.05 and p<0.01, respectively). Our results suggest that exercise, especially intense exercise, improves QoL and survival rate and prevents muscle atrophy. These data suggest that exercise is an optimal prehabilitation choice to alleviate the negative impacts of cancer cachexia. PMID:27994677

  10. 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

  11. 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.

  12. Activin signal promotes cancer progression and is involved in cachexia in a subset of pancreatic cancer.

    Science.gov (United States)

    Togashi, Yosuke; Kogita, Akihiro; Sakamoto, Hiroki; Hayashi, Hidetoshi; Terashima, Masato; de Velasco, Marco A; Sakai, Kazuko; Fujita, Yoshihiko; Tomida, Shuta; Kitano, Masayuki; Okuno, Kiyotaka; Kudo, Masatoshi; Nishio, Kazuto

    2015-01-28

    We previously reported that activin produces a signal with a tumor suppressive role in pancreatic cancer (PC). Here, the association between plasma activin A and survival in patients with advanced PC was investigated. Contrary to our expectations, however, patients with high plasma activin A levels had a significantly shorter survival period than those with low levels (median survival, 314 days vs. 482 days, P = 0.034). The cellular growth of the MIA PaCa-2 cell line was greatly enhanced by activin A via non-SMAD pathways. The cellular growth and colony formation of an INHBA (beta subunit of inhibin)-overexpressed cell line were also enhanced. In a xenograft study, INHBA-overexpressed cells tended to result in a larger tumor volume, compared with a control. The bodyweights of mice inoculated with INHBA-overexpressed cells decreased dramatically, and these mice all died at an early stage, suggesting the occurrence of activin-induced cachexia. Our findings indicated that the activin signal can promote cancer progression in a subset of PC and might be involved in cachexia. The activin signal might be a novel target for the treatment of PC.

  13. Pentoxifylline treatment in patients with cancer cachexia: A double-blind, randomized, placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Valiollah Mehrzad

    2016-01-01

    Conclusion: Results of this study demonstrated that Pentoxifylline in the treatment of cancer cachexia did not have any effect in weight gain and arm circumference in cachectic patients. But in short-term (1 month treatment, QOL was improved in these patients. And after 2 month treatment this was not effective compared to placebo.

  14. Alterations in inflammatory biomarkers and energy intake in cancer cachexia: a prospective study in patients with inoperable pancreatic cancer.

    Science.gov (United States)

    Bye, Asta; Wesseltoft-Rao, Nima; Iversen, Per Ole; Skjegstad, Grete; Holven, Kirsten B; Ulven, Stine; Hjermstad, Marianne J

    2016-06-01

    Chronic systemic inflammatory response is proposed as an underlying mechanism for development of cancer cachexia. We conducted a prospective study to examine changes in inflammatory biomarkers during the disease course and the relationship between inflammatory biomarkers and cachexia in patients with inoperable pancreatic cancer. Twenty patients, median (range) age 67.5 (35-79) years, 5 females, were followed for median 5.5 (1-12) months. Cachexia was diagnosed according to the 2011 consensus-based classification system (weight loss >5 % past six months, BMI 2 %, or sarcopenia) and the modified Glasgow Prognostic score (mGPS) that combines CRP and albumin levels. Inflammatory biomarkers were measured by enzyme immunoassays. The patients had increased levels of most inflammatory biomarkers, albeit not all statistically significant, both at study entry and close to death, indicating ongoing inflammation. According to the consensus-based classification system, eleven (55 %) patients were classified as cachectic upon inclusion. They did not differ from non-cachectic patients with regard to inflammatory biomarkers or energy intake. According to the mGPS, seven (35 %) were defined as cachectic and had a higher IL-6 (p cachexia.

  15. 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.

  16. Forebrain patterns of c-Fos and FosB induction during cancer-associated anorexia-cachexia in rat.

    Science.gov (United States)

    Konsman, Jan Pieter; Blomqvist, Anders

    2005-05-01

    Forebrain structures are necessary for the initiation of food intake and its coupling to energy expenditure. The cancer-related anorexia-cachexia syndrome is typified by a prolonged increase in metabolic rate resulting in body weight loss which, paradoxically, is accompanied by reduced food intake. The aim of the present work was to study the forebrain expression of Fos proteins as activation markers and thus to identify potential neurobiological mechanisms favouring catabolic processes or modulating food intake in rats suffering from cancer-related anorexia-cachexia. Neurons in forebrain structures showing most pronounced induction of Fos proteins were further identified neurochemically. To provoke anorexia-cachexia, cultured Morris hepatoma 7777 cells were injected subcutaneously in Buffalo rats. This resulted in a slowly growing tumour inducing approximately 7% body weight loss and a 20% reduction in food intake when the tumour represented 1-2% of body mass. Anorexia-cachexia in these animals was found to be accompanied by Fos induction in several hypothalamic nuclei including the paraventricular and ventromedial hypothalamus, in the parastrial nucleus, the amygdala, the bed nucleus of the stria terminalis, ventral striatal structures and the piriform and somatosensory cortices. Neurochemical identification revealed that the vast majority of FosB-positive neurons in the nucleus accumbens, ventral caudate-putamen and other ventral striatal structures contained prodynorphin or proenkephalin mRNA. These findings indicate that forebrain structures that are part of neuronal networks modulating catabolic pathways and food ingestion are activated during tumour-associated anorexia-cachexia and may contribute to the lack of compensatory eating in response to weight loss characterizing this syndrome.

  17. Combined treatment of carfilzomib and z-VAD-fmk inhibits skeletal proteolysis and apoptosis and ameliorates cancer cachexia.

    Science.gov (United States)

    Wang, Qiang; Li, Chunhong; Peng, Xudong; Kang, Qingjie; Deng, Dawei; Zhang, Liuping; Zheng, Yueyong; Wang, Chaoyi; Qiao, Zhongpeng; Guo, Dunwei; You, Song; Tang, Hua

    2015-04-01

    The purpose of the study was to evaluate the therapeutic benefit of treatments with carfilzomib (CFZ) and z-VAD-fmk in a mouse model of cancer-induced cachexia. The model of cancer-associated cachexia was generated by injecting murine C26 adenocarcinoma cells into BALB/C mice. CFZ and z-VAD-fmk were administered individually or in combination at 5 and 12 days after inoculation. Changes in body weight, gastrocnemius muscle mass, tumor burden, spontaneous activity, survival, and metabolic profiles were noted. Also evaluated were the circulatory levels of renin and angiotensin II, and levels of apoptotic, proteolytic, and renin-angiotensin system-associated markers and transcription factor 2 (ATF2) in gastrocnemius muscle. The CFZ and z-VAD-fmk treatments were associated with less muscle wasting, reduced tumor burden, modulated metabolism, higher levels of glucose, albumin, and total proteins, and lower levels of triglyceride fatty acids, more spontaneous physical activity, and longer survival in C26-inoculated mice compared with PBS-treated cachectic mice. CFZ and z-VAD-fmk treatments resulted in higher levels of caspase-3 and BAX and lower level of BCL-XL in gastrocnemius muscles and altered the level of proteins in the renin-angiotensin system. The combined treatment administered 5 days after C26 inoculation was more effective than other regimens. Combined treatment with CFZ and z-VAD-fmk early in the development of cachexia was associated with signs of less proteolysis and apoptosis and less severe cachexia in a mouse model of cancer-induced cachexia.

  18. Pancreatic cancer-induced cachexia is Jak2-dependent in mice.

    Science.gov (United States)

    Gilabert, Marine; Calvo, Ezequiel; Airoldi, Ana; Hamidi, Tewfik; Moutardier, Vincent; Turrini, Olivier; Iovanna, Juan

    2014-10-01

    Cancer cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and it is one of the most frequent causes of death. Severe wasting accounts for more than 80% in patients with advanced pancreatic cancer. Here we wanted to define, by using an microarray approach and the Pdx1-cre;LSL-Kras(G12D) ;INK4a/arf(fl/fl) mice model, the pathways involved in muscle, liver, and white adipose tissue wasting. These mice, which develop systematically pancreatic cancer, successfully reproduced many human symptoms afflicted with this disease, and particularly cachexia. Using the profiling analysis of pancreatic cancer-dependent cachectic tissues we found that Jak2/Stat3 pathways, p53 and NFkB results activated. Thus, our interest was focused on the Jak2 pathways because it is pharmacologically targetable with low toxicity and FDA approved drugs are available. Therefore, Pdx1-cre;LSL-Kras(G12D) ;INK4a/arf(fl/fl) mice were treated with the Jak2 inhibitor AG490 compound daily starting at 7 weeks old and for a period of 3 weeks and animals were sacrificed at 10 weeks old. Body weight for control mice was 27.84 ± 2.14 g, for untreated Pdx1-cre;LSL-Kras(G12D) ;INK4a/arf(fl/fl) was 14.97 ± 1.99 g, whereas in animals treated with the AG490 compound the weight loss was significantly less to 24.53 ± 2.04 g. Treatment with AG490 compound was efficient since phosphorylation of Jak2 and circulating interleukin-6 (IL6) levels were significantly reduced in cachectic tissues and in mice respectively. In conclusion, we found that Jak2/Stat3-dependent intracellular pathway plays an essential role since its pharmacological inhibition strongly attenuates cachexia progression in a lethal transgenic pancreatic cancer model.

  19. Loss of muscle mass: Current developments in cachexia and sarcopenia focused on biomarkers and treatment.

    Science.gov (United States)

    Drescher, Cathleen; Konishi, Masaaki; Ebner, Nicole; Springer, Jochen

    2016-01-01

    Loss of muscle mass arises from an imbalance of protein synthesis and protein degradation. Potential triggers of muscle wasting and function are immobilization, loss of appetite, dystrophies and chronic diseases as well as aging. All these conditions lead to increased morbidity and mortality in patients, which makes it a timely matter to find new biomarkers to get a fast clinical diagnosis and to develop new therapies. This mini-review covers current developments in the field of biomarkers and drugs on cachexia and sarcopenia. Here, we reported about promising markers, e.g. tartrate-resistant acid phosphatase 5a (TRACP5a), and novel substances like Epigallocatechin-3-gallate (EGCg). In summary, the progress to combat muscle wasting is in full swing and perhaps diagnosis of muscle atrophy and of course patient treatments could be soon supported by improved and more helpful strategies.

  20. 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.

  1. Perspectives of health care professionals on cancer cachexia: results from three global surveys

    Science.gov (United States)

    Muscaritoli, M.; Rossi Fanelli, F.; Molfino, A.

    2016-01-01

    Background Cachexia has a high prevalence in cancer patients and negatively impacts prognosis, quality of life (QOL), and tolerance/response to treatments. This study reports the results of three surveys designed to gain insights into cancer cachexia (CC) awareness, understanding, and treatment practices among health care professionals (HCPs). Methods Surveys were conducted globally among HCPs involved in CC management. Topics evaluated included definitions and synonyms of CC, diagnosis and treatment practices, and goals and desired improvements of CC treatment. Results In total, 742 HCPs from 14 different countries participated in the surveys. The majority (97%) of participants were medical oncologists or hematologists. CC was most frequently defined as weight loss (86%) and loss of appetite (46%). The terms loss of weight and decreased appetite (51% and 34%, respectively) were often provided as synonyms of CC. Almost half (46%) of the participants reported diagnosing CC and beginning treatment if a patient experienced a weight loss of 10%. However, 48% of the participants would wait until weight loss was ≥15% to diagnose CC and start treatment. HCPs also reported that 61%–77% of cancer patients do not receive any prescription medication for CC before Stage IV of disease is reached. Ability to promote weight gain was rated as the most important factor for selecting CC treatment. Key goals of treatment included ensuring that patients can cope with the cancer and treatment and have a QOL benefit. HCPs expressed desire for treatments with a more CC-specific mode of action and therapies that enhance QOL. Conclusions These surveys underscore the need for increased awareness among HCPs of CC and its management. PMID:28007753

  2. A systematic review on the role of vitamins, minerals, proteins, and other supplements for the treatment of cachexia in cancer: a European Palliative Care Research Centre cachexia project.

    Science.gov (United States)

    Mochamat; Cuhls, Henning; Marinova, Milka; Kaasa, Stein; Stieber, Christiane; Conrad, Rupert; Radbruch, Lukas; Mücke, Martin

    2017-02-01

    We provide a systematic review to support the European Palliative Care Research Collaboration development of clinical guidelines for cancer patients suffering from cachexia. CENTRAL, MEDLINE, PsycINFO, ClinicalTrials.gov, and a selection of cancer journals have been searched up until 15 April 2016. The systematic literature research yielded 4214 publications with 21 of these included in the final evaluation. Regarding minerals, our search identified only one study examining the use of magnesium with no effect on weight loss. As far as vitamins are concerned, vitamin E in combination with omega-3 fatty acids displayed an effect on survival in a single study, vitamin D showed improvement of muscle weakness in prostate cancer patients, and vitamin C supplementation led to an improvement of various quality of life aspects in a sample with a variety of cancer diagnoses. For proteins, a combination therapy of β-hydroxy-β-methylbutyrate (HMB), arginine, and glutamine showed an increase in lean body mass after 4 weeks in a study of advanced solid tumour patients, whereas the same combination did not show a benefit on lean body mass in a large sample of advanced lung and other cancer patients after 8 weeks. L-carnitine led to an increase of body mass index and an increase in overall survival in advanced pancreatic cancer patients. Adverse effects of food supplementation were rare and showed mild intensity. There is not enough solid evidence for the use of minerals, vitamins, proteins, or other supplements in cancer. No serious adverse effects have been reported with dietary supplementation.

  3. 癌性恶病质内科治疗进展%Medical treatment of cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    张红欣; 张增叶

    2008-01-01

    Cancer cachexia is a common syndrome in advanced cancer patients.It is the interactive re-sult between tissue of tumor and organism.Tissue of tumor affects organism by producing cytokines and special tumor agents,meanwhile the reaction of acute phase and aeuroendocrine reaction happen in all over the body.Age,physical activity level and abnormal metabolism of muscle protein of patients are also correlated to cancer cachexia.Now clinical strategy to cancer cachexia is to improve symptoms of patients,such as anorexia,and So on.Along with elucidating the nosogenesis of cancer cachexia,the research of drugs having identified targets becomes focus.%癌症恶病质是晚期肿瘤患者常见综合征,是肿瘤组织与机体相互作用的结果,肿瘤组织产生炎性细胞因子及特定因子作用于机体,而机体应激产生全身急性反应及神经内分泌反应,如此相互作用导致恶病质.同时,患者的年龄、体力活动水平和肌肉蛋白的异常代谢也被认为与癌性恶病质发生相关.目前,临床治疗癌性恶病质的策略主要针对改善患者的厌食症状,随着对发病机制深入了解,一些具有明确靶点的药物研究成为热点.

  4. New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line.

    Science.gov (United States)

    Terawaki, Kiyoshi; Sawada, Yumi; Kashiwase, Yohei; Hashimoto, Hirofumi; Yoshimura, Mitsuhiro; Suzuki, Masami; Miyano, Kanako; Sudo, Yuka; Shiraishi, Seiji; Higami, Yoshikazu; Yanagihara, Kazuyoshi; Kase, Yoshio; Ueta, Yoichi; Uezono, Yasuhito

    2014-02-15

    Cancer cachexia (CC), a syndrome characterized by anorexia and body weight loss due to low fat-free mass levels, including reduced musculature, markedly worsens patient quality of life. Although stomach cancer patients have the highest incidence of cachexia, few experimental models for the study of stomach CC have been established. Herein, we developed stomach CC animal models using nude rats subcutaneously implanted with two novel cell lines, i.e., MKN45c185, established from the human stomach cancer cell line MKN-45, and 85As2, derived from peritoneal dissemination of orthotopically implanted MKN45c185 cells in mice. Both CC models showed marked weight loss, anorexia, reduced musculature and muscle strength, increased inflammatory markers, and low plasma albumin levels; however, CC developed earlier and was more severe in rats implanted with 85As2 than in those implanted with MKN45cl85. Moreover, human leukemia inhibitory factor (LIF), a known cachectic factor, and hypothalamic orexigenic peptide mRNA levels increased in the models, whereas hypothalamic anorexigenic peptide mRNA levels decreased. Surgical removal of the tumor not only abolished cachexia symptoms but also reduced plasma LIF levels to below detectable limits. Importantly, oral administration of rikkunshito, a traditional Japanese medicine, substantially ameliorated CC-related anorexia and body composition changes. In summary, our novel peritoneal dissemination-derived 85As2 rat model developed severe cachexia, possibly caused by LIF from cancer cells, that was ameliorated by rikkunshito. This model should provide a useful tool for further study into the mechanisms and treatment of stomach CC.

  5. The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising candidate for the treatment of cancer cachexia.

    Science.gov (United States)

    Dallmann, R; Weyermann, P; Anklin, C; Boroff, M; Bray-French, K; Cardel, B; Courdier-Fruh, I; Deppe, H; Dubach-Powell, J; Erb, M; Haefeli, R H; Henneböhle, M; Herzner, H; Hufschmid, M; Marks, D L; Nordhoff, S; Papp, M; Rummey, C; Santos, G; Schärer, F; Siendt, H; Soeberdt, M; Sumanovski, L T; Terinek, M; Mondadori, C; Güven, N; Feurer, A

    2011-09-01

    BACKGROUND: Under physiological conditions, the melanocortin system is a crucial part of the complex network regulating food intake and energy expenditure. In pathological states, like cachexia, these two parameters are deregulated, i.e., food intake is decreased and energy expenditure is increased-a vicious combination leading to catabolism. Agouti-related protein (AgRP), the endogenous antagonist at the melanocortin-4 receptor (MC-4R), was found to increase food intake and to reduce energy expenditure. This qualifies MC-4R blockade as an attractive mode of action for the treatment of cachexia. Based on this rationale, a novel series of small-molecule MC-4R antagonists was designed, from which the orally active compound BL-6020/979 (formerly known as SNT207979) emerged as the first promising development candidate showing encouraging pre-clinical efficacy and safety properties which are presented here. METHODS AND RESULTS: BL-6020/979 is an orally available, selective and potent MC-4R antagonist with a drug-like profile. It increased food intake and decreased energy expenditure in healthy wild-type but not in MC-4R deficient mice. More importantly, it ameliorated cachexia-like symptoms in the murine C26 adenocarcinoma model; with an effect on body mass and body composition and on the expression of catabolic genes. Moreover, BL-6020/979 showed antidepressant-like properties in the chronic mild stress model in rats and exhibits a favorable safety profile. CONCLUSION: The properties of BL-6020/979 demonstrated in animal models and presented here make it a promising candidate suitable for further development towards a first-in-class treatment option for cachexia that potentially opens up the opportunity to treat two hallmarks of the disease, i.e., decreased food intake and increased energy expenditure, with one drug.

  6. The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising candidate for the treatment of cancer cachexia

    OpenAIRE

    Dallmann, R; Weyermann, P.; Anklin, C; Boroff, M.; Bray-French, K.; Cardel, B; Courdier-Fruh, I; Deppe, H.; Dubach-Powell, J.; Erb, M.; Haefeli, R H; Henneböhle, M; Herzner, H.; Marks, D. L.; Hufschmid, M

    2011-01-01

    BACKGROUND: Under physiological conditions, the melanocortin system is a crucial part of the complex network regulating food intake and energy expenditure. In pathological states, like cachexia, these two parameters are deregulated, i.e., food intake is decreased and energy expenditure is increased-a vicious combination leading to catabolism. Agouti-related protein (AgRP), the endogenous antagonist at the melanocortin-4 receptor (MC-4R), was found to increase food intake and to reduce energy ...

  7. 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.

  8. The MEK-Inhibitor Selumetinib Attenuates Tumor Growth and Reduces IL-6 Expression but Does Not Protect against Muscle Wasting in Lewis Lung Cancer Cachexia

    Science.gov (United States)

    Au, Ernie D.; Desai, Aditya P.; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2017-01-01

    Cachexia, or wasting of skeletal muscle and fat, afflicts many patients with chronic diseases including cancer, organ failure, and AIDS. Muscle wasting reduces quality of life and decreases response to therapy. Cachexia is caused partly by elevated inflammatory cytokines, including interleukin-6 (IL-6). Others and we have shown that IL-6 alone is sufficient to induce cachexia both in vitro and in vivo. The mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor Selumetinib has been tested in clinical trials for various cancers. Moreover, Selumetinib has also been shown to inhibit the production of IL-6. In a retrospective analysis of a phase II clinical trial in advanced cholangiocarcinoma, patients treated with Selumetinib experienced significant gains in skeletal muscle vs. patients receiving standard therapy. However, the use of Selumetinib as a treatment for cachexia has yet to be investigated mechanistically. We sought to determine whether MEK inhibition could protect against cancer-induced cachexia in mice. In vitro, Selumetinib induced C2C12 myotube hypertrophy and nuclear accretion. Next we tested Selumetinib in the Lewis lung carcinoma (LLC) model of cancer cachexia. Treatment with Selumetinib reduced tumor mass and reduced circulating and tumor IL-6; however MEK inhibition did not preserve muscle mass. Similar wasting was seen in limb muscles of Selumetinib and vehicle-treated LLC mice, while greater fat and carcass weight loss was observed with Selumetinib treatment. As well, Selumetinib did not block wasting in C2C12 myotubes treated with LLC serum. Taken together, out results suggest that this MEK inhibitor is not protective in LLC cancer cachexia despite lowering IL-6 levels, and further that it might exacerbate tumor-induced weight loss. Differences from other studies might be disease, species or model-specific. PMID:28149280

  9. The abridged patient-generated subjective global assessment is a useful tool for early detection and characterization of cancer cachexia.

    Science.gov (United States)

    Vigano, Antonio L; di Tomasso, Jonathan; Kilgour, Robert D; Trutschnigg, Barbara; Lucar, Enriqueta; Morais, José A; Borod, Manuel

    2014-07-01

    Cancer cachexia (CC) is a syndrome characterized by wasting of lean body mass and fat, often driven by decreased food intake, hypermetabolism, and inflammation resulting in decreased lifespan and quality of life. Classification of cancer cachexia has improved, but few clinically relevant diagnostic tools exist for its early identification and characterization. The abridged Patient-Generated Subjective Global Assessment (aPG-SGA) is a modification of the original Patient-Generated Subjective Global Assessment, and consists of a four-part questionnaire that scores patients' weight history, food intake, appetite, and performance status. The purpose of this study was to determine whether the aPG-SGA is associated with both features and clinical sequelae of cancer cachexia. In this prospective cohort study, 207 advanced lung and gastrointestinal cancer patients completed the following tests: aPG-SGA, Edmonton Symptom Assessment System, handgrip strength, a complete blood count, albumin, apolipoprotein A and B, and C-reactive protein. Ninety-four participants with good performance status as assessed by the Eastern Cooperative Oncology Group Performance Status completed additional questionnaires and underwent body composition testing. Of these, 68 patients tested for quadriceps strength and completed a 3-day food recall. Multivariable regression models revealed that higher aPG-SGA scores (≥9 vs 0 to 1) are significantly associated (Pcachexia, such as higher white blood cell counts (10.0 vs 6.7×10(9)/L; lower hemoglobin (115.6 vs 127.7 g/L), elevated C-reactive protein (42.7 vs 18.2 mg/L [406.7 vs 173.3 nmol/L]); decreased anthropometric and physical measures, such as body mass index (22.5 vs 27.1); fat mass (14.4 vs 26.0 kg), handgrip (24.7 vs 34.9 kg) and leg strength; an average 12% greater length of hospital stay; a dose reduction in chemotherapy; and increased mortality. Given its association with the main features of cancer cachexia and its ease of use, the a

  10. Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    Mariano Malaguarnera; Corrado Risino; Maria Pia Gargante; Giovanni Oreste; Gloria Barone; Anna Veronica Tomasello; Mario Costanzo; Matteo Angelo Cannizzaro

    2006-01-01

    AIM: To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia.METHODS: Fifthy-five cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations,including examination of the levels of various forms of carnitine present in serum (i.e., long-chain acylcarnitine,short-chain acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects.RESULTS: When the cachectic patients with gastrointestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8 μmol/L in free carnitine (P<0.005), 0.04 μmol/L in long chain acylcarnitine (P<0.05), 8.7 μmol/L in total carnitine (P<0.001). In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2μmol/L in free carnitine (P<0.001), 4.60 μmol/L in short chain acylcarnitine (P<0.001), and 0.60 μmol/L in long-chain acylcarnitine (P<0.005) and 17.4 μmol/L in total carnitine (P<0.001). In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5 μmol/L in free carnitine (P<0.001), 5.2 μmol/L in short-chain acylcarnitine (P< 0.001), 1.0 μmol/L in long chain acylcarnitine (P <0.001), and 21.8μmol/L in total carnitine (P<0.001).CONCLUSION: Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients.

  11. 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.

  12. 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.

  13. 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.

  14. Cachexia and adiposity in rheumatoid arthritis. Relevance for disease management and clinical outcomes.

    Science.gov (United States)

    Challal, Salima; Minichiello, Emeline; Boissier, Marie-Christophe; Semerano, Luca

    2016-03-01

    Altered body composition is a frequent finding in rheumatoid arthritis and is associated with the two major outcomes of the disease: disability and cardiovascular mortality. It is estimated that up to two thirds of patients may be affected by loss of lean mass, the so-called rheumatoid cachexia. Hence, body weight being equal, the relative amount of lean mass is lower and that of body fat is higher in rheumatoid arthritis patients vs. healthy controls. Both disease-related factors and other factors, like drug treatments, physical activity and nutrition contribute to modify body composition in rheumatoid arthritis. The effect of pharmacological treatments, and notably of anti-TNF drugs, on body composition is controversial. Conversely, training programs to stimulate muscle growth can restore lean mass and reduce adiposity. There is good evidence that amelioration of body composition ameliorates function and reduces disability. Currently, there is no evidence that interventions that modify body composition can reduce cardiovascular morbidity and mortality in rheumatoid arthritis.

  15. Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth.

    Science.gov (United States)

    Shukla, Surendra K; Dasgupta, Aneesha; Mehla, Kamiya; Gunda, Venugopal; Vernucci, Enza; Souchek, Joshua; Goode, Gennifer; King, Ryan; Mishra, Anusha; Rai, Ibha; Nagarajan, Sangeetha; Chaika, Nina V; Yu, Fang; Singh, Pankaj K

    2015-12-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic cancer cells. Silibinin treatment diminishes c-MYC expression, a key regulator of cancer metabolism. Furthermore, we observed reduced STAT3 signaling in silibinin-treated cancer cells. Overexpression of constitutively active STAT3 was sufficient to substantially revert the silibinin-induced downregulation of c-MYC and the metabolic phenotype. Our in vivo investigations demonstrate that silibinin reduces tumor growth and proliferation in an orthotopic mouse model of pancreatic cancer and prevents the loss of body weight and muscle. It also improves physical activity including grip strength and latency to fall in tumor-bearing mice. In conclusion, silibinin-induced metabolic reprogramming diminishes cell growth and cachectic properties of pancreatic cancer cells and animal models.

  16. [VEGF in the cancer anorexia-cachexia syndrome in patients with lung cancer].

    Science.gov (United States)

    Weryńska, Bozena; Kosacka, Monika; Gołecki, Marcin; Jankowska, Renata

    2006-01-01

    Cancer anorexia-cachexia syndrome( CACS) occurs in 30-80% of patients with cancer. CACS is connected with poor prognosis and higher risk of treatment complications. CACS belongs to the common cause of death in cancer patients. Main role in the development of this syndrome play cytokines like TNF, interleukin 1 and 6 and interferon alpha and gamma. The importance of a lot of other substances is still unknown. VEGF promotes new vessels development,enhance vascular permeability and plays a role in inflammatory reaction. The aim of this study was comparison of VEGF levels in patients with lung cancer with and without CACS and in control group. The serum levels of VEGF were measured by ELISA method. The VEGF was significatly higher in patients with lung cancer then in control group (p = 0.004). There were no correlations between VEGF and weight lost, histological type and stage of disease. This suggest that VEGF doesnt play a role in development of CACS.

  17. 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.

  18. Progress in Cancer Cachexia Pathogenesis and Treatment%癌症恶病质发病机制与治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    温宏升; 阎飞(综述); 秦贤举(审校)

    2016-01-01

    癌症恶病质( CC)是晚期恶性肿瘤常见并发症。近十年,尽管 CC 发生机制的研究取得了一些新进展,但其治疗尚缺乏理想的方法。 CC病理生理机制复杂,涉及系统性炎症反应、脂肪代谢和蛋白质代谢等多种因素。 CC的成功治疗也有赖于多途径干预,包括营养支持和多种药物联合运用。目前临床上用于治疗CC的药物有沙利度胺、非甾体消炎药类、孕酮类等;另外,一些根据其发病机制设计的新药尚处于临床研究阶段(如ALD518、OHR/AVR118等)。%Cancer cachexia is a common complication of advanced cancer.Over the last decade,we have gained new insight into the pathophysiology of cancer cachexia.Unfortunately,its treatment remains a chal-lenge.Cancer cachexia is a multifactorial syndrome,which is mainly related to systemic inflammatory reac-tion,lipid metabolism and protein metabolism ,etc.The successful management of cancer cachexia will likely require the multimodal approaches that include nutritional support and combination of pharmaceutical inter-ventions.The current drugs in clinic for treatment of cancer cachexia include thalidomide,nonsteroid anti-inflammatory drugs,progesterone drugs,etc.In addition,some new drugs designed according to the cancer cachexia pathogenesis are still in the clinical research stage,such as ALD518,OHR/AVR118,etc.

  19. Baicalin, a component of Scutellaria baicalensis, alleviates anorexia and inhibits skeletal muscle atrophy in experimental cancer cachexia.

    Science.gov (United States)

    Li, Bin; Wan, Lili; Li, Yan; Yu, Qi; Chen, Pengguo; Gan, Run; Yang, Quanjun; Han, Yonglong; Guo, Cheng

    2014-12-01

    Inflammatory responses are key contributors to cancer cachexia and foster a complex cascade of biological outcomes. Baicalin is a natural compound derived from Scutellaria baicalensis that possesses anti-inflammatory properties in many diseases; therefore, the aim of this study was to verify whether baicalin could ameliorate cachexia in a CT26 adenocarcinoma-induced model. Tumour-bearing and control mice were injected with CT26 adenocarcinoma cells and phosphate-buffered saline (PBS), respectively, and baicalin was administered intraperitoneally for 15 days. During the study, food intake, body weight, major organ weight, gastrocnemius muscle weight, tibialis muscle weight, epididymal fat weight and serum cytokine levels were measured and evaluated. Additionally, the expression of two E3 ubiquitin ligases and NF-κB pathway proteins were detected by Western blot. The total food intake in tumour-bearing mice receiving baicalin from days 1-16, as well as the average food intake on days 10-16, were less than normal but were significantly higher than in vehicle-treated tumour-bearing mice. Loss of tumour-free body mass in vehicle-treated tumour-bearing mice was significantly increased compared with control mice and tumour-bearing mice receiving baicalin. Serum cytokines, including tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were lowered in tumour-bearing mice treated with baicalin. Gastrocnemius muscle, epididymal fat, heart and kidney weight were significantly greater in the baicalin treatment groups compared with the vehicle-treated tumour-bearing mice. In addition, the expression of two E3 ubiquitin ligases, as well as phospho-p65, was significantly downregulated, whereas the expression of IκBα was up-regulated in tumour-bearing mice treated with baicalin, as determined by Western blotting. The present study demonstrates that baicalin effectively ameliorates anorexia by inhibiting cytokine expression and prevents skeletal muscle atrophy most

  20. Fisiopatología de la caquexia neoplásica Pathophysiology of neoplasic cachexia

    Directory of Open Access Journals (Sweden)

    J. M. Argilés

    2006-05-01

    , gastrointestinal metabolic, nutritional and endocrine mechanisms. The cancer patient suffers from anorexia which results in early saciety and a reduction of appetite. Sometimes, the causes of the anorectic response are derived from the antitumoral treatment (chemotherapy, radiotherapy or immunotherapy, in some cases vomiting resulting in altered food intake. Alterations in the food taste and smell perception in addition to psychological dearrangements might also lead to the anorexia. Sometimes the tumour may play a direct effect when it is localised in either the hypothalamus or the digestive apparatus. However, in the majority of cases the origin of the anorexia associated with cancer cachexia seems to be due to the metabolic alterations induced by tumour burden. Different factors of both humoral and tumoral origin play a role in cancer anorexia. For instance, tumour necrosis factor (TNF- , a cytokine responsible for a great part of the metabolic alterations characteristic of cancer cachexia seems to be involved. In conclusion, the cancer anorexia seems to be more an effect than the cause of the weight loss and in fact the decrease in food intake might take place after weight loss is evident. In any case, the malnutrition associated with a decrease of food intake worsens the cachectic state, favouring a kind of a positive feed-back mechanism that finally leads to the patient's death.

  1. 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

  2. Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later.

    Science.gov (United States)

    Ryan, Aoife M; Power, Derek G; Daly, Louise; Cushen, Samantha J; Ní Bhuachalla, Ēadaoin; Prado, Carla M

    2016-05-01

    An awareness of the importance of nutritional status in hospital settings began more than 40 years ago. Much has been learned since and has altered care. For the past 40 years several large studies have shown that cancer patients are amongst the most malnourished of all patient groups. Recently, the use of gold-standard methods of body composition assessment, including computed tomography, has facilitated the understanding of the true prevalence of cancer cachexia (CC). CC remains a devastating syndrome affecting 50-80 % of cancer patients and it is responsible for the death of at least 20 %. The aetiology is multifactorial and complex; driven by pro-inflammatory cytokines and specific tumour-derived factors, which initiate an energy-intensive acute phase protein response and drive the loss of skeletal muscle even in the presence of adequate food intake and insulin. The most clinically relevant phenotypic feature of CC is muscle loss (sarcopenia), as this relates to asthenia, fatigue, impaired physical function, reduced tolerance to treatments, impaired quality of life and reduced survival. Sarcopenia is present in 20-70 % depending on the tumour type. There is mounting evidence that sarcopenia increases the risk of toxicity to many chemotherapy drugs. However, identification of patients with muscle loss has become increasingly difficult as 40-60 % of cancer patients are overweight or obese, even in the setting of metastatic disease. Further challenges exist in trying to reverse CC and sarcopenia. Future clinical trials investigating dose reductions in sarcopenic patients and dose-escalating studies based on pre-treatment body composition assessment have the potential to alter cancer treatment paradigms.

  3. Proteomic analysis of media from lung cancer cells reveals role of 14-3-3 proteins in cachexia

    Directory of Open Access Journals (Sweden)

    Julie eMcLean

    2015-04-01

    Full Text Available AIMS: At the time of diagnosis, 60% of lung cancer patients present with cachexia, a severe wasting syndrome that increases morbidity and mortality. Tumors secrete multiple factors that contribute to cachectic muscle wasting, and not all of these factors have been identified. We used Orbitrap electrospray ionization mass spectrometry to identify novel cachexia-inducing candidates in media conditioned with Lewis lung carcinoma cells (LCM. Results: One-hundred and fifty-eight proteins were confirmed in three biological replicates. Thirty-three were identified as secreted proteins, including 14-3-3 proteins, which are highly conserved adaptor proteins known to have over 200 binding partners. We confirmed the presence of extracellular 14-3-3 proteins in LCM via western blot and discovered that LCM contained less 14-3-3 content than media conditioned with C2C12 myotubes. Using a neutralizing antibody, we depleted extracellular 14-3-3 proteins in myotube culture medium, which resulted in diminished myosin content. We identified the proposed receptor for 14-3-3 proteins, CD13, in differentiated C2C12 myotubes and found that inhibiting CD13 via Bestatin also resulted in diminished myosin content. Conclusions: Our novel findings show that extracellular 14-3-3 proteins may act as previously unidentified myokines and may signal via CD13 to help maintain muscle mass.

  4. 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.

  5. Experimental Cancer Cachexia Changes Neuron Numbers and Peptide Levels in the Intestine: Partial Protective Effects after Dietary Supplementation with L-Glutamine

    Science.gov (United States)

    Vicentini, Geraldo E.; Fracaro, Luciane; de Souza, Sara R. G.; Martins, Heber A.; Guarnier, Flávia A.; Zanoni, Jacqueline N.

    2016-01-01

    Gastrointestinal dysmotility frequently occurs in cancer cachexia and may result from damage to enteric innervation caused by oxidative stress, especially due to glutathione depletion. We assessed the effect of dietary supplementation with 20 g/kg l-glutamine (a glutathione precursor) on the intrinsic innervation of the enteric nervous system in healthy and Walker 256 tumor-bearing Wistar rats during the development of experimental cachexia (14 days), in comparison with non-supplemented rats, by using immunohistochemical methods and Western blotting. The total neural population and cholinergic subpopulation densities in the myenteric plexus, as well as the total population and VIPergic subpopulation in the submucosal plexus of the jejunum and ileum, were reduced in cachectic rats, resulting in adaptive morphometric alterations and an increase in vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) expression, suggesting a neuroplastic response. l-glutamine supplementation prevented decrease in myenteric neuronal density in the ileum, morphometric alterations in the neurons and nerve fibers (in both the plexuses of the jejunum and ileum), and the overexpression of VIP and CGRP. Cancer cachexia severely affected the intrinsic innervation of the jejunum and ileum to various degrees and this injury seems to be associated with adaptive neural plasticity. l-glutamine supplementation presented partial protective effects on the enteric innervation against cancer cachexia, possibly by attenuating oxidative stress. PMID:27635657

  6. The mechanism of cancer cachexia and the potential treatment%肿瘤恶病质的机制及可能的治疗

    Institute of Scientific and Technical Information of China (English)

    周开国; 何桂珍

    2011-01-01

    恶病质是宿主和肿瘤相互作用的结果,主要表现为短期内消瘦、营养不良等.宿主和肿瘤分泌的炎性因子和恶病质特异因子是引起恶病质的主要原因.单纯的高能饮食不能改善病情,近来应用免疫营养、传统医学和药物干预等防治手段能减轻恶病质体质量下降和延长生存期,有可喜的应用前景.%Cachexia is the result of interaction between host and tumor, with main manifestations like weight loss in short-term, malnutrition and so on. The inflammatoru cytokines secreted by host cells and cachexia specific factor secreted by tumor are the main causes of cachexia. High-energy diet alone can not improve the condition. Recently, immunonutrition, traditional medicine and drug intervention can alleviate the weight loss and prolong survival in cachexia.

  7. 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.

  8. Cancer cachexia raises the plasma concentration of oxymorphone through the reduction of CYP3A but not CYP2D6 in oxycodone-treated patients.

    Science.gov (United States)

    Naito, Takafumi; Tashiro, Masaki; Ishida, Takuya; Ohnishi, Kazunori; Kawakami, Junichi

    2013-08-01

    This study evaluated the plasma concentrations of oxycodone and its demethylates and opioid-induced adverse effects based on cachexia stage in cancer patients receiving oxycodone. Seventy patients receiving oxycodone for cancer pain were enrolled. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined at the titration dose. Opioid-induced adverse effects were monitored for 2 weeks after the titration. Plasma concentrations of oxycodone and oxymorphone but not noroxycodone in patients with a GPS of 2 were significantly higher than that with a GPS of 0. The metabolic ratios of noroxycodone but not oxymorphone to oxycodone in patients with a GPS of 1 and 2 were significantly lower than in those with a GPS of 0. A higher GPS was associated with a higher incidence of somnolence, while the GPS did not affect the incidence of vomiting. Plasma concentrations of oxycodone and oxymorphone were not associated with the incidence of adverse effects. In conclusion, cancer cachexia raised the plasma exposures of oxycodone and oxymorphone through the reduction of CYP3A but not CYP2D6. Although the cachexia elevated the incidence of somnolence, alterations in their pharmacokinetics were not associated with the incidence.

  9. Sunitinib prevents cachexia and prolongs survival of mice bearing renal cancer by restraining STAT3 and MuRF-1 activation in muscle.

    Science.gov (United States)

    Pretto, Francesca; Ghilardi, Carmen; Moschetta, Michele; Bassi, Andrea; Rovida, Alessandra; Scarlato, Valentina; Talamini, Laura; Fiordaliso, Fabio; Bisighini, Cinzia; Damia, Giovanna; Bani, Maria Rosa; Piccirillo, Rosanna; Giavazzi, Raffaella

    2015-02-20

    Tyrosine kinase inhibitors, affecting angiogenesis, have shown therapeutic efficacy in renal cell carcinoma (RCC). The increased overall survival is not fully explained by their anti-tumor activity, since these drugs frequently induce disease stabilization rather than regression. RCC patients frequently develop cachectic syndrome. We used the RXF393 human renal carcinoma xenograft that recapitulates the characteristics of the disease, including the growth in the mouse kidney (orthotopic implantation), and the induction of cachexia with subsequent premature death. Sunitinib prevents body weight loss and muscle wasting and significantly improves the survival of RXF393-bearing nude mice. The anti-cachectic effect was not associated to direct anti-tumor activity of the drug. Most relevant is the ability of sunitinib to reverse the cachectic phenotype and rescue the animals from the loss of fat tissue. Body weight loss is prevented also in mice bearing the C26 colon carcinoma, classically reported to induce cachexia in immunocompetent mice. Among the mechanisms, we herein show that sunitinib is able to restrain the overactivation of STAT3 and MuRF-1 pathways, involved in enhanced muscle protein catabolism during cancer cachexia. We suggest that off-target effects of angiogenesis inhibitors targeting STAT3 are worth considering as a therapeutic option for patients who develop cachexia, independently of their anti-tumor activity.

  10. 肿瘤恶病质与白色脂肪组织棕色化%Cancer cachexia and white adipose tissue browning

    Institute of Scientific and Technical Information of China (English)

    张叁涛; 杨红枚

    2016-01-01

    晚期肿瘤患者多伴有恶病质的发生,这些患者身体功能减退,对抗肿瘤治疗的耐受力变差,存活率明显下降。目前临床上用于治疗肿瘤恶病质的手段十分有限,深入了解肿瘤恶病质发生、发展的分子机制,并从新的角度探索有效治疗手段是必要而迫切的。最新的研究表明,白色脂肪组织棕色化是肿瘤恶病质一项重要的特征,白色脂肪组织的这种转变导致脂肪动员增加,并使机体能量过度消耗,这可能是肿瘤恶病质发生、发展的重要原因之一。文章主要对肿瘤恶病质和白色脂肪组织棕色化的定义及特点进行了概述,并结合相关研究的最新进展,探讨了肿瘤恶病质研究的新方向。%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.

  11. Muscle-specific E3 ubiquitin ligases are involved in muscle atrophy of cancer cachexia: an in vitro and in vivo study.

    Science.gov (United States)

    Yuan, Lei; Han, Jun; Meng, Qingyang; Xi, Qiulei; Zhuang, Qiulin; Jiang, Yi; Han, Yusong; Zhang, Bo; Fang, Jing; Wu, Guohao

    2015-05-01

    Muscle atrophy F-Box (MAFbx)/atrogin-1 and muscle ring-finger-1 (MuRF-1) have been identified as two muscle-specific E3 ubiquitin ligases that are highly expressed in skeletal muscle during muscle atrophy. However, the role of muscle-specific E3 ubiquitin ligases during the process of muscle atrophy of cancer cachexia remains largely unknown. In the present study, we analyzed the expression of atrogin-1 and MuRF-1 in the skeletal muscle of patients with malignant and benign disease. The possible mechanisms were studied both in a colon 26-induced cancer cachexia mouse model and in tumor necrosis factor-α (TNF-α) induced atrophy C2C12 cells. Our results demonstrated that atrogin-1 and MuRF-1 tended to be increased in the skeletal muscle of patients with malignant disease even before weight loss. Non-tumor body weights and gastrocnemius weights were significantly decreased while expression levels of ubiquitin proteasome pathway associated genes (atrogin-1, MuRF-1, ubiquitin and E2-14K) were upregulated in cancer cachexia mice. Significant myotube atrophy with atrogin-1 overexpression was observed in the C2C12 cells treated with TNF-α. Meanwhile, knockdown of atrogin-1 by small interfering RNA (siRNA) protected C2C12 cells from the adverse effect of TNF-α. In conclusion, muscle-specific E3 ubiquitin ligases were upregulated during cancer cachexia, and atrogin-1 may be a potential molecular target for treating muscle atrophy induced by cancer cachexia.

  12. Research progress of the mechanism of cancer cachexia%癌性恶病质发病机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    王中霞; 欧阳兵; 季旭明; 王文革

    2011-01-01

    目的:总结癌性恶病质发病机制及实验研究现状,探讨厌食、机体代谢异常、细胞因子在恶病质发生中的作用机制,整理恶病质基础实验研究进展.方法:应用PubMed及CNKI期刊全文数据库检索系统,以“恶病质”、“发病机制”和“实验研究”等为主题词,检索2005-2011年的相关文献,共检索到61篇文献.纳入标准:1)恶病质的发病机制研究;2)厌食、机体代谢异常、细胞因子在恶病质发生中的作用;3)有关恶病质的基础实验研究.根据纳入标准符合分析的文献有29篇.结果:恶病质是晚期癌症患者死亡的重要原因.厌食、机体代谢异常、细胞因子变化促使了恶病质的发生,许多学者通过基础实验研究了恶病质动物模型及药物干预作用,并取得了良好效果.结论:恶病质发病机制较为复杂,有待进一步深入系统研究.药物干预尤其是中医中药的治疗,是防治恶病质的一个重要措施.%OBJECTIVE: To summarize the mechanism and experimental study of cachexia, and discuss the mechanism and classify advanced of experimental study of the cachexia. METHODS: A total of 61 articles on tubular carcinoma of breast published between 2005 - 2011 were retrived in Pubmed and CNKI with the key of words of "cachexia, mechanism,experimental study". Inclusion criteria: 1) The mechanism of cachexia; 2) The function of Anorexia, body metabolic abnormalities and cell factor in cachexia; 3) Basic experimental study related to cachexia. Twenty-nine papers were collected. RESULTS: Cachexia is the important reason for the die of terminal cancer patients. Anorexia, body metabolic abnormalities and cell factor are the primary mechanism. And many researchers studied the model of animals and the interference therapy and achieved good results. CONCLUSION; The mechanism of cachexia becomes more systematic, and drug interference especially the interference of Traditional Chinese Medicine which is an

  13. 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.

  14. Muscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging and chronic diseases: from sarcopenic obesity to cachexia.

    Science.gov (United States)

    Biolo, Gianni; Cederholm, Tommy; Muscaritoli, Maurizio

    2014-10-01

    Skeletal muscle is the most abundant body tissue accounting for many physiological functions. However, muscle mass and functions are not routinely assessed. Sarcopenia is defined as skeletal muscle loss and dysfunction in aging and chronic diseases. Inactivity, inflammation, age-related factors, anorexia and unbalanced nutrition affect changes in skeletal muscle. Mechanisms are difficult to distinguish in individual subjects due to the multifactorial character of the condition. Sarcopenia includes both muscle loss and dysfunction which induce contractile impairment and metabolic and endocrine abnormalities, affecting whole-body metabolism and immune/inflammatory response. There are different metabolic trajectories for muscle loss versus fat changes in aging and chronic diseases. Appetite regulation and physical activity affect energy balance and changes in body fat mass. Appetite regulation by inflammatory mediators is poorly understood. In some patients, inflammation induces anorexia and fat loss in combination with sarcopenia. In others, appetite is maintained, despite activation of systemic inflammation, leading to sarcopenia with normal or increased BMI. Inactivity contributes to sarcopenia and increased fat tissue in aging and diseases. At the end of the metabolic trajectories, cachexia and sarcopenic obesity are paradigms of the two patient categories. Pre-cachexia and cachexia are observed in patients with cancer, chronic heart failure or liver cirrhosis. Sarcopenic obesity and sarcopenia with normal/increased BMI are observed in rheumatoid arthritis, breast cancer patients with adjuvant chemotherapy and in most of patients with COPD or chronic kidney disease. In these conditions, sarcopenia is a powerful prognostic factor for morbidity and mortality, independent of BMI.

  15. L-carnitine intervention in energy metabolism of cancer cachexia patients%左卡尼汀干预癌性恶液质能量代谢

    Institute of Scientific and Technical Information of China (English)

    吴丹; 李苏宜

    2016-01-01

    Objective As cancer cachexia patients present low level of L-carnitine and abnormal energy metabolism, this study is to evaluate the impact of L-carnitine on energy metabolism of cancer cachexia patients. Methods We collected and analysed the results from the domestic and foreign published literature related to L-carnitine, cancer cachexia and energy metabolism in recent years. Results L-carnitine can ameliorate lipid metabolism disorders in cachexia patients, ameliorate anorexia by adjusting fatty acid metabolism in the hypothalamus;signiifcantly decrease activities of proteasome related with protein metabolism, inhibit proteolysis, improve performance status and fatigue of patients;improve insulin resistance and increase insulin sensitivity. Conclusions The intervention of L-carnitine in cancer cachexia is worth paying attention to, but still need large sample research evidence to conifrm, its underlying mechanisms also need further research.%目的癌性恶液质患者左旋肉碱水平低下,能量代谢异常,本文探讨左卡尼汀对癌性恶液质能量代谢的影响。方法回顾近年来国内外发表的有关左卡尼汀和癌性恶液质、能量代谢的中英文文献,并进行综合评述。结果左卡尼汀能够纠正恶液质患者脂质代谢紊乱,通过调节下丘脑脂肪酸代谢而改善恶液质者厌食;显著降低蛋白质代谢相关蛋白酶体活性,抑制蛋白质水解,改善患者一般情况,改善乏力;改善胰岛素抵抗,提高胰岛素敏感性。结论左卡尼汀干预癌性恶液质能量代谢值得关注,但尚需大样本研究证据证实,潜在机制也需要进一步深入研究。

  16. Tratamiento farmacológico de la anorexia-caquexia cancerosa Pharmacological therapy of cancer anorexia-cachexia

    Directory of Open Access Journals (Sweden)

    D. Cardona

    2006-05-01

    megestrol y los corticosteroides serán de primera línea de elección en el síndrome de anorexia-caquexia por incrementar el apetito y el primero el peso y repercutir en la mejoría de la calidad de vida y de confort en los enfermos con cáncer avanzado.Anorexia is one of the most common symptoms of patients with advanced cancer and it presents as loss of appetite due to satiety. On the other hand, cachexia is described in those patients with unwanted weight loss. Cancerous processes produce an energy unbalance by decreased food intake and increased catabolism, resulting in a clearly negative balance. Several factors determining cachexia are observed, from metabolic unbalances produced by tumoral products and endocrine impairments or the inflammatory response produced by cytokines, all of them leading to higher lipolysis, loss of muscle protein, and anorexia. Besides, causes of anorexia are multiple, from chemotherapy agents, radiotherapy, or immunotherapy, which may produce different degrees of nausea, vomiting, diarrhea, and also leading to impairments of taste and smell, to obstruction of the digestive tract, pain, depression, constipation, etc. From the knowledge of the different mechanisms producing the anorexia-cachexia syndrome, hypercaloric diets for artificial nutrition have been studied with varying success, and different drugs with a positive effect on appetite gain such as progestogens, steroids, and with lesser clinical evidence cannabinoids, cyproheptadine, mirtazapine (antidepressant, and olanzapine (antipsychotic. Other drugs have been studied because of their anti-inflammatory properties, anti-cytokine, such as melatonin, polyunsaturated omega-3 fatty acids, pentoxifylline, and thalidomide; with the exception of the latter, clinical data are still scant for daily usage. Similarly happens with testosterone-derived anabolic drugs or with metabolism inhibitors such as hydrazine sulfate. With no doubt, progestogens, especially megestrol, and corticosteroids

  17. Non Digestible Oligosaccharides Modulate the Gut Microbiota to Control the Development of Leukemia and Associated Cachexia in Mice.

    Directory of Open Access Journals (Sweden)

    Laure B Bindels

    Full Text Available We tested the hypothesis that changing the gut microbiota using pectic oligosaccharides (POS or inulin (INU differently modulates the progression of leukemia and related metabolic disorders. Mice were transplanted with Bcr-Abl-transfected proB lymphocytes mimicking leukemia and received either POS or INU in their diet (5% for 2 weeks. Combination of pyrosequencing, PCR-DGGE and qPCR analyses of the 16S rRNA gene revealed that POS decreased microbial diversity and richness of caecal microbiota whereas it increased Bifidobacterium spp., Roseburia spp. and Bacteroides spp. (affecting specifically B. dorei to a higher extent than INU. INU supplementation increased the portal SCFA propionate and butyrate, and decreased cancer cell invasion in the liver. POS treatment did not affect hepatic cancer cell invasion, but was more efficient than INU to decrease the metabolic alterations. Indeed, POS better than INU delayed anorexia linked to cancer progression. In addition, POS treatment increased acetate in the caecal content, changed the fatty acid profile inside adipose tissue and counteracted the induction of markers controlling β-oxidation, thereby hampering fat mass loss. Non digestible carbohydrates with prebiotic properties may constitute a new nutritional strategy to modulate gut microbiota with positive consequences on cancer progression and associated cachexia.

  18. Cancer cachexia diagnosis and therapy%癌性恶病质的诊断和治疗

    Institute of Scientific and Technical Information of China (English)

    刘子凤; 李贵新

    2012-01-01

    癌性恶病质传统的治疗方法一般在晚期进行干预,以增加营养摄人为主,并且多以体重做为判断疗效的标准,大量临床试验证明效果并不理想.最近的研究表明在恶病质早期即以蛋白酶体为靶点进行靶向治疗,并与传统治疗相结合,治疗后核因子-KB(NF-KB)水平降低,肌纤维蛋白破坏终止,血浆蛋白及瘦体数量升高,功能好转.%Cancer cachexia(CC)caused by cancer is a syndrome with complicated symptoms.Traditional therapies usually give interventions for more nutrition intake at CC late stage and take weight as the outcome marker.Lots of clinical trials demonstrate that the effect is not satisfactory.Recent studies show that the level of NF-KB decreased,termination of the breakdown of myofibrillar proteins,the serum proteins and lean body mass increased and function improvement after targeting proteasome at early stage of CC combined with traditional therapy.

  19. Complete reversal of muscle wasting in experimental cancer cachexia: Additive effects of activin type II receptor inhibition and β-2 agonist.

    Science.gov (United States)

    Toledo, Míriam; Busquets, Sílvia; Penna, Fabio; Zhou, Xiaolan; Marmonti, Enrica; Betancourt, Angelica; Massa, David; López-Soriano, Francisco J; Han, H Q; Argilés, Josep M

    2016-04-15

    Formoterol is a highly potent β2-adrenoceptor-selective agonist, which is a muscle growth promoter in many animal species. Myostatin/activin inhibition reverses skeletal muscle loss and prolongs survival of tumor-bearing animals. The aim of this investigation was to evaluate the effects of a combination of the soluble myostatin receptor ActRIIB (sActRIIB) and the β2-agonist formoterol in the cachectic Lewis lung carcinoma model. The combination of formoterol and sActRIIB was extremely effective in reversing muscle wasting associated with experimental cancer cachexia in mice. Muscle weights from tumor-bearing animals were completely recovered following treatment and this was also reflected in the measured grip strength. This combination increased food intake in both control and tumor-bearing animals. The double treatment also prolonged survival significantly without affecting the weight and growth of the primary tumor. In addition, it significantly reduced the number of metastasis. Concerning the mechanisms for the preservation of muscle mass during cachexia, the effects of formoterol and sActRIIB seemed to be additive, since formoterol reduced the rate of protein degradation (as measured in vitro as tyrosine release, using incubated isolated individual muscles) while sActRIIB only affected protein synthesis (as measured in vivo using tritiated phenylalanine). Formoterol also increased the rate of protein synthesis and this seemed to be favored by the presence of sActRIIB. Combining formoterol and sActRIIB seemed to be a very promising treatment for experimental cancer cachexia. Further studies in human patients are necessary and may lead to a highly effective treatment option for muscle wasting associated with cancer.

  20. Inhibition of Stat3 activation suppresses caspase-3 and the ubiquitin-proteasome system, leading to preservation of muscle mass in cancer cachexia.

    Science.gov (United States)

    Silva, Kleiton Augusto Santos; Dong, Jiangling; Dong, Yanjun; Dong, Yanlan; Schor, Nestor; Tweardy, David J; Zhang, Liping; Mitch, William E

    2015-04-24

    Cachexia occurs in patients with advanced cancers. Despite the adverse clinical impact of cancer-induced muscle wasting, pathways causing cachexia are controversial, and clinically reliable therapies are not available. A trigger of muscle protein loss is the Jak/Stat pathway, and indeed, we found that conditioned medium from C26 colon carcinoma (C26) or Lewis lung carcinoma cells activates Stat3 (p-Stat3) in C2C12 myotubes. We identified two proteolytic pathways that are activated in muscle by p-Stat3; one is activation of caspase-3, and the other is p-Stat3 to myostatin, MAFbx/Atrogin-1, and MuRF-1 via CAAT/enhancer-binding protein δ (C/EBPδ). Using sequential deletions of the caspase-3 promoter and CHIP assays, we determined that Stat3 activation increases caspase-3 expression in C2C12 cells. Caspase-3 expression and proteolytic activity were stimulated by p-Stat3 in muscles of tumor-bearing mice. In mice with cachexia caused by Lewis lung carcinoma or C26 tumors, knock-out of p-Stat3 in muscle or with a small chemical inhibitor of p-Stat3 suppressed muscle mass losses, improved protein synthesis and degradation in muscle, and increased body weight and grip strength. Activation of p-Stat3 stimulates a pathway from C/EBPδ to myostatin and expression of MAFbx/Atrogin-1 and increases the ubiquitin-proteasome system. Indeed, C/EBPδ KO decreases the expression of MAFbx/Atrogin-1 and myostatin, while increasing muscle mass and grip strength. In conclusion, cancer stimulates p-Stat3 in muscle, activating protein loss by stimulating caspase-3, myostatin, and the ubiquitin-proteasome system. These results could lead to novel strategies for preventing cancer-induced muscle wasting.

  1. Effect of KLT treatment on life quality and cachexia factors in elderly patients with cancer cachexia%康莱特对老年癌症恶病质患者生存质量影响及恶病质因子的调控

    Institute of Scientific and Technical Information of China (English)

    苏爱梅; 许旌; 王颖捷; 王惠; 张洪

    2012-01-01

    目的 探讨康莱特对老年癌症恶病质( cancer cachexia,CC)患者的生存质量影响及时恶病质因子的调控作用. 方法 62例2009年1月至2011年4月住院的老年癌症患者,根据CC的诊断标准,各项评分>5分者42例入组,分别用康莱特进行干预,比较干预前后患者KPS评分、三酰甘油(TG)、血红蛋白(HB)、血清白蛋白(ALB)、肿瘤坏死因子(TNF-2α)及新的恶病质因子锌-α2-糖蛋白(zinc-alpha 2-glycoprotein,ZAG)的变化. 结果 治疗后与治疗前相比,患者KPS评分升高,血HB和TNF-2α升高、ZAG降低(P<0.05);TG明显升高(P<0.01).ALB治疗前后比较没有统计学差异(P>0.05). 结论 康莱特可以降低老年癌症患者的恶病质因子TNF-2α、ZAG水平,有改善患者恶病质症状,提高患者生存质量的作用.%Objective To study the effect of KLT treatment on life quality and the variation of plasma cachexia factors in elderly patients with cancer cachexia(CC). Methods Among the 62 patients of cancer, 42 of CC received KLT injection treatment for 21 days. Triglyceride (TG), hemoglobin ( HB ) , blood albumin ( ALB), tumor necrosis factor 2a (TNF-2α), zinc-alpha 2-glycoprotein(ZAG) and KPS scores were observed and compared before and after treatment. Results The levels of ZAG and TNF-2α were decreased and the HB, TG, KPS scores were increased significantly after the treatment (P 0. 05). Conclusions KLT treatment can decrease cachexia factors TNF-2a and new cachexia factors ZAG, and can improve life quality of elderly patients with CC.

  2. 蛋白水解诱导因子在消化系统肿瘤癌性恶液质患者中的表达及其作用%Proteolysis induce factor in the digestive systematic cancer cachexia patients: its expression and role in cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    韩寓嵩; 庄秋林; 吴国豪

    2012-01-01

    Objective To demonstrate the expression of proteolysis induce factor (PIF) in the gastrointestinal (GI) cancer cachexia patients and evaluate its role in cancer cachexia.Methods Examination of PIF was performed in urine samples from 28 GI cancer cachexia patients,13 GI cancer patients without cachexia,and 12 weight loss patients with benign disease.PIF was added to the mice cultured C2C 12 muscle cells,then the protein kinase B (Akt) phosphorylation and morphological change were measured.Results The positive rate of PIF in urine of 28 cancer cachexia patients was 53.6% (15/28).In the other two groups,no positive result was detected.PIF could successfully induce Akt phosphorylation,cell atrophy,metamorphosis,and death.The peak of this phosphorylation could be detected after half an hour of the initiation of PIF at a concentration of 4 nmoL/L.Conclusions PIF is specifically and highly expressed in GI cancer cachexia patients'urine.PIF can induce cancer cachexia possibly by activating Akt phosphorylation and inducing downstream proteolysis.%目的 观察蛋白水解诱导因子(PIF)在消化系统肿瘤癌性恶液质(CC)患者中的表达情况,探讨其在消化系统肿瘤CC发生发展中的作用.方法 检测28例消化系统肿瘤CC患者、13例消化系统肿瘤非CC患者和12例非肿瘤消瘦患者尿液中PIF的表达.将PIF作用于离体小鼠C2C12细胞,测定细胞蛋白激酶B(Akt)磷酸化程度并观察细胞形态.结果 CC患者PIF阳性率为53.6%(15/28),其他两组均无PIF阳性表达.4 nmol/L的PIF蛋白作用于C2C12细胞0.5 h后,细胞磷酸化Akt的表达量增高,并且细胞呈现不同程度的萎缩、变形或死亡.结论 PIF特异性高表达于消化系统肿瘤CC患者的尿液中,PIF可能通过激活Akt的磷酸化从而引发下游的蛋白水解途径导致消化系统肿瘤CC.

  3. 癌性恶病质肌肉减少的病理生理机制和治疗方法%Pathophysiologic mechanisms and therapeutic methods of sarcopenia in cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    汪立鑫; 周岩冰

    2016-01-01

    Sarcopenia is a major clinical characteristic of cancer cachexia .The main pathophysiologic mechanism of sarcopenia related to cancer cachexia is abnormality between anabolic and catabolic pathways of muscle mediated by chronic inflammation .The major treatments for sarcopenia in cancer cachexia currently in-clude hormone therapy , nutrition support , exercise therapy , and other medications , which could not effectively prevent muscle loss or enhance muscle function .Better understanding of the pathogenetic processes of cancer cachexia-related sarcopenia may help in finding targets for an effective therapy .%肌肉减少是处于恶病质期癌症患者的主要临床特征之一。癌性恶病质下肌肉减少的主要病理生理机制是在慢性炎症介导下出现的肌肉合成代谢和分解代谢通路异常。目前针对癌性恶病质肌肉减少的治疗主要包括激素治疗、营养支持、运动疗法和其他药物,但目前仍无法实际有效地阻止肌肉丢失和增强肌肉功能。增进了解癌性恶病质下肌肉减少的发病机制有助于寻找多靶点治疗方法。

  4. Relationship of cytokine level with cancer cachexia and its clinical research%癌性恶病质与细胞因子相关性的临床研究

    Institute of Scientific and Technical Information of China (English)

    何文杰; 任宏轩; 王羽丰

    2011-01-01

    Objective To study the expression of cytokine in the cancer cachexia patients and to discuss the relationship with cancer cachexia. Methods To compare the IL-1 、IL-6 、TNF-α、IFN-γ levels with 80 cases patients of cancer cachexia 、40 cases healthy people and 40 cases patients of non-cancer cachexia. To oral medroxyprogesterone with the 80 cases patients of cancer cachexia and give the nutritional support of four weeks. Four weeks later, to detect the levels of IL-1 、IL-6 、TNF-α IFN-γand compare with pre-treatment. Results Compared cancer cachexia group with non-cancer cachexia group and healthy group, the levels of IL-1 、IL-6 、TNF-α 、IFN-γ increased. P < 0. 05 , there were significances in statistics; The 80 cases patients of cancer cachexia through four weeks treated. the levels of IL-1 、IL-6 、TNF-α 、IFN-γ decreased. P < 0. 05 , there were significances in statistics. Conclusion Cytokines are relevant to the cancer cachexia and playing an important role.%目的 探讨细胞因子在癌性恶病质患者中的表达情况及与癌性恶病质发生、发展的相关性.方法 对80例癌性恶病质患者、40例门诊体检的健康人和40例非恶病质癌症患者血清中的IL-1、IL-6、TNF-α、IFN-γ水平相互比较.对80例癌性恶病质患者,采用甲羟孕酮片及营养支持治疗4周后检测其血清中的IL-1、IL-6、TNF-α、IFN-γ水平,并与治疗前的水平进行比较.结果 癌性恶病质组与健康组、非恶病质癌症组比较,IL-1、IL-6、TNF-α、IFN-γ水平升高(P<0.05);癌性恶病质组治疗后IL-1、IL-6、TNF-α、IFN-γ水平下降(P<0.05).结论 细胞因子与癌性恶病质的发生、发展相关,并扮演着重要的角色.

  5. 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

  6. 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

  7. 癌症恶病质的中医药研究进展%The progress of Chinese medical research on cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    汪欣文; 郝淑兰; 刘丽坤

    2008-01-01

    Patients with advanced cancer often suffer from cachexia. The researches on cancer cachexis using Chinese medicine include theoretic and clinical studies. The thesis also includes:a systemic comparison to review the progress in recent years, a simple analysis on the problem and shortages of the researches, and a suggestion on the future direction,%癌症恶病质是晚期肿瘤患者常见的一种病症.从临床和基础研究两个方面回顾了近年来中医在癌症恶病质方面研究的进展情况.并对目前研究中存在的问题和今后的研究方向做了简要评述.

  8. The ghrelin receptor agonist HM01 mimics the neuronal effects of ghrelin in the arcuate nucleus and attenuates anorexia-cachexia syndrome in tumor-bearing rats.

    Science.gov (United States)

    Borner, Tito; Loi, Laura; Pietra, Claudio; Giuliano, Claudio; Lutz, Thomas A; Riediger, Thomas

    2016-07-01

    The gastric hormone ghrelin positively affects energy balance by increasing food intake and reducing energy expenditure. Ghrelin mimetics are a possible treatment against cancer anorexia-cachexia syndrome (CACS). This study aimed to characterize the action of the nonpeptidergic ghrelin receptor agonist HM01 on neuronal function, energy homeostasis and muscle mass in healthy rats and to evaluate its possible usefulness for the treatment of CACS in a rat tumor model. Using extracellular single-unit recordings, we tested whether HM01 mimics the effects of ghrelin on neuronal activity in the arcuate nucleus (Arc). Furthermore, we assessed the effect of chronic HM01 treatment on food intake (FI), body weight (BW), lean and fat volumes, and muscle mass in healthy rats. Using a hepatoma model, we investigated the possible beneficial effects of HM01 on tumor-induced anorexia, BW loss, muscle wasting, and metabolic rate. HM01 (10(-7)-10(-6) M) mimicked the effect of ghrelin (10(-8) M) by increasing the firing rate in 76% of Arc neurons. HM01 delivered chronically for 12 days via osmotic minipumps (50 μg/h) increased FI in healthy rats by 24%, paralleled by increased BW, higher fat and lean volumes, and higher muscle mass. Tumor-bearing rats treated with HM01 had 30% higher FI than tumor-bearing controls and were protected against BW loss. HM01 treatment resulted in higher muscle mass and fat mass. Moreover, tumor-bearing rats reduced their metabolic rate following HM01 treatment. Our studies substantiate the possible therapeutic usefulness of ghrelin receptor agonists like HM01 for the treatment of CACS and possibly other forms of disease-related anorexia and cachexia.

  9. Sarcopenia da caquexia reumatoide: conceituação, mecanismos, consequências clínicas e tratamentos possíveis Sarcopenia in rheumatoid cachexia: definition, mechanisms, clinical consequences and potential therapies

    Directory of Open Access Journals (Sweden)

    Oswaldo Melo da Rocha

    2009-06-01

    Full Text Available A caquexia relacionada à artrite reumatoide é conceituada como perda involuntária de massa magra, predominantemente de músculo esquelético, que também ocorre em vísceras e sistema imune, com massa gorda estável ou um pouco elevada e com pequena ou nenhuma perda de peso. A causa é multifatorial, incluindo a produção acentuada de citocinas, principalmente TNF± e IL-1², diminuição da ação periférica da insulina e pouca atividade física. A caquexia se faz presente em doentes com AR ativa ou mesmo inativa. Neste artigo discutem-se aspectos relacionados à patogenia, implicações clínicas e possíveis opções terapêuticas.Rheumatoid cachexia can be defined as an involuntary loss of body cell mass, which predominates in skeletal muscle, but is also observed in the viscera and immune system. It occurs with little or no weight loss in the presence of stable or increased fat mass. The etiology is likely multifactorial, and involves excessive inflammatory cytokine production, namely excess tumor necrosis factor-± and interleukin-1² production, reduced peripheral insulin action, and low habitual physical activity. Cachexia occurs in active rheumatoid arthritis and even in the presence of disease control. In this article, we discuss the pathogenesis of rheumatoid cachexia, its clinical implications and potential therapies.

  10. Contribución del soporte nutricional a combatir la caquexia cancerosa Contribution of nutritional support to fight cancer cachexia

    Directory of Open Access Journals (Sweden)

    M. Planas

    2006-05-01

    seems necessary. N-3 fatty acids, especially eicosapentaenoic acid may have anticachectic properties. Although further trials are necessary the limited results available suggests that nutritional supplements enriched with EPA may reverse cachexia in cancer patients.

  11. MCG101-induced cancer anorexia-cachexia features altered expression of hypothalamic Nucb2 and Cartpt and increased plasma levels of cocaine- and amphetamine-regulated transcript peptides.

    Science.gov (United States)

    Burgos, Jonathan R; Iresjö, Britt-Marie; Smedh, Ulrika

    2016-04-01

    The aim of the present study was to explore central and peripheral host responses to an anorexia-cachexia producing tumor. We focused on neuroendocrine anorexigenic signals in the hypothalamus, brainstem, pituitary and from the tumor per se. Expression of mRNA for corticotropin-releasing hormone (CRH), cocaine- and amphetamine-regulated transcript (CART), nesfatin-1, thyrotropin (TSH) and the TSH receptor were explored. In addition, we examined changes in plasma TSH, CART peptides (CARTp) and serum amyloid P component (SAP). C57BL/6 mice were implanted with MCG101 tumors or sham-treated. A sham-implanted, pair‑fed (PF) group was included to delineate between primary tumor and secondary effects from reduced feeding. Food intake and body weight were measured daily. mRNA levels from microdissected mouse brain samples were assayed using qPCR, and plasma levels were determined using ELISA. MCG101 tumors expectedly induced anorexia and loss of body weight. Tumor-bearing (TB) mice exhibited an increase in nesfatin-1 mRNA as well as a decrease in CART mRNA in the paraventricular area (PVN). The CART mRNA response was secondary to reduced caloric intake whereas nesfatin-1 mRNA appeared to be tumor-specifically induced. In the pituitary, CART and TSH mRNA were upregulated in the TB and PF animals compared to the freely fed controls. Plasma levels for CARTp were significantly elevated in TB but not PF mice whereas levels of TSH were unaffected. The plasma CARTp response was correlated to the degree of inflammation represented by SAP. The increase in nesfatin-1 mRNA in the PVN highlights nesfatin-1 as a plausible candidate for causing tumor-induced anorexia. CART mRNA expression in the PVN is likely an adaptation to reduced caloric intake secondary to a cancer anorexia-cachexia syndrome (CACS)‑inducing tumor. The MCG101 tumor did not express CART mRNA, thus the elevation of plasma CARTp is host derived and likely driven by inflammation.

  12. Relationship between serum myostatin and gastric carcinoma-associated cachexia%血清肌抑素水平与胃癌恶病质的关系

    Institute of Scientific and Technical Information of China (English)

    曹淑成; 丁连安; 牛冬光; 王琳; 姚如永

    2012-01-01

    Objective To observe the changes of serum myostatin (MSTN) level in patients with gastric carcinoma-associated cachexia and to investigate the relationship between MSTN and tumor necrosis factor α (TNF-α) preliminarily.Methods Eighty patients with gastric cancer were divided into two groups based on their Patient-Generated Subjective Global Assessement (PG-SGA) scores:gastric carcinoma-associated cachexia group (GCC group,32 cases; PG-SGA stage C) and gastric carcinoma non-cachexia group (GCNC,48 cases; PG-SGA stage A + B).The serum MSTN and TNF-α levels were measured by enzyme linked immunosorbent assay,and relevant parameters including height,weight,albumin,hemoglobin,and C-reactive protein were also recorded before operation.Eighty healthy adults were chosen as the control group.Results The serum MSTN level in the GCC group [(1.36 ±0.50) μg/L] was significantly higher than that in the GCNC group [(0.91 ±0.49) μg/L; x2 =14.67,P =0.00],whereas the serum MSTN level in the GCNC group was significantly higher than that in the control group [(0.70 ± 0.37) μg/L; x2 =36.45,P =0.00].Serum MSTN level was not correlated with TNF-α in the GCC group (r=0.18,P=0.31),GCNC group (r=0.08,P=0.58),or control group (r=-0.16,P=0.16).Conclusions Serum MSTN level is elevated in patients with gastric carcinoma-associated cachexia.However,it is not correlated with serum TNF-α.%目的 观察胃癌恶病质患者血清肌抑素水平变化,并初步探讨肌抑素与肿瘤坏死因子-α的相关性.方法 根据整体营养状况主观评估(PG-SGA)分级将80例胃癌患者分成胃癌恶病质组(PG-SGAC级,32例)和胃癌非恶病质组(PG-SGA A+B级,48例),采用ELISA法测定血清肌抑素和肿瘤坏死因子-α水平,并记录身高、体质量、总蛋白、白蛋白、血红蛋白、C-反应蛋白等指标.对照组为健康体检者80例,同法测定并记录上述指标.结果 胃癌恶病质组的血清肌抑素水平为(1.36±0.50) μg/L,显著

  13. 实验性癌性恶病质药物干预研究%Intervention study of drugs on experimental cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    张红欣; 姜达; 张富同; 韩鲁军

    2012-01-01

    ,但吲哚美辛升高血糖作用较强,鱼油+吲哚美辛在降低甘油三酯、胆固醇方面显示了优势.%Objective To study the different effects on cancer cachexia among indomethacin,thalidomide,fish oil+thalidomide.fish oil, and nutritional support.Methods 80 BALB/C mice were randomly divided into eight groups, including healthy control group, cancer cachexia group (negative control group) .medroxy progesterone group (positive control group),indomethacin group,thalidomide group,fish oil+indomethacin group,fish oil group,nutritional support group.Each group included 10 mice.Then, the animal model of experiment about cancer cachexia was established, the drug intervention was given.Body mass was measured daily.The serum Level of total protein, blood glucose, triglyceride,cholesterol, tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) ,and the activity of nuclear factor-κB (NF-κB) in spleen were detected.Results The level of blood glucose in indomethacin group was higher than that of cancer cachexia group, medroxy progesterone group, thalidomide group, fish oil+indomethacin group, fish oil group, nutritional support group, respectively (7.45±0.15) mmol/L vs (4.86±0.37) mmol/L, (6.51 ± 0.39) mmol/L, (6.50±0.04) mmol/L, (6.47±0.13) mmol/L, (6.49±0.32) mmol/L, (6.35±0.33) mmol/L(all P <0.05).The level of triglyceride in fish oil±indomethacin group was significantly lower than that of all other above six groups, respectively (2.06±0.02) mmol/L vs (6.91 ±0.23) mmol/L, (3.44±0.12) mmol/L,(7.13±0.24) mmol/L, (3.48± 0.03) mmol/L,(2.06±0.02) mmol/L, (3.51±0.20) mmol/L, (3.45±0.22) mmol/L(all P <0.05).The level of cholesterol in fish oil±indomethacin group was lower than that of all above six other groups, (2.11 ±0.41) mmol/L vs(5.18±0.80) mmol/L, (3.17 ±0.45) mmol/L, (3.76 ±0.60) mmol/L, (3.87 ± 0.82) mmol/L, (3.68 ± 0.61) mmol/L,(3.86±0.64) mmol/L(all P <0.05).The serum level of TNF-α in groups of indomethacin,thalidomide,fish oil

  14. Effect of Yangzheng Xiaoji Capsule on Quality of Life in Patients with Cancer Cachexia%养正消积胶囊对癌症恶病质患者生活质量的影响

    Institute of Scientific and Technical Information of China (English)

    毕俊芳; 李雪松; 胡秉贤; 顾敏; 赵杨

    2016-01-01

    Objective:To observe the effect of Yangzheng Xiaoji Capsule on quality of life in patients with cancer cachexia.Methods:A total of 70 cases of cancer cachexia patients were randomly divided into 2groups.On the basis of nutritional support and symptomatic treatment,the treatment group took Yangzheng Xiaoji Capsule and the control group megestrol acetate tablets.The observation period was 1 month.The life quality evaluation scale (FAACT) was completed with the data before and after treatment.Results After treatment,in terms of physiological status,additional concerns and the total score in the treatment group increased significantly comparing with those in the control group(P <0.05).Conclusion:Yangzheng Xiaoji Capsule has a positive effect on quality of life in patients with cancer cachexia.%目的:观察养正消积胶囊对癌症恶病质患者生活质量的影响.方法:将70例癌症恶病质患者随机分为两组,两组患者均给予饮食指导及一般营养支持治疗,治疗组服用养正消积胶囊,对照组服用甲地孕酮片,观察周期1个月.治疗前后分别记录生活质量评价量表(FAACT).结果:养正消积胶囊组在生理状况、附加关注和总评分方面,显著优于甲地孕酮对照组(P<0.05).结论:养正消积胶囊对癌症恶病质患者生活质量的改善具有积极的作用.

  15. Fisiología de la sarcopenia: Similitudes y diferencias con la caquexia neoplásica Psysiology of sarcopenia: Similarities and differences with neoplasic cachexia (muscle impairments in cancer and aging

    Directory of Open Access Journals (Sweden)

    Josep M. Argilés

    2006-05-01

    Full Text Available Las alteraciones que acontecen durante el proceso canceroso y el envejecimiento comparten bastantes vías metabólicas así como también mediadores. Dado que afectan a gran cantidad de personas, la caquexia cancerosa y la sarcopenia del envejecimiento podrían ser dianas para futuras investigaciones clínicas. La caquexia cancerosa es un síndrome caracterizado por una gran pérdida de peso, anorexia, astenia y anemia. De hecho, muchos de los pacientes que mueren de cáncer avanzado sufren caquexia. El grado de caquexia está inversamente correlacionado con el tiempo de supervivencia de los pacientes y siempre implica una mala prognosis. En los últimos años, las enfermedades e incapacidades relacionadas con la edad han despertado un gran interés e importancia sanitaria. Concretamente, el desgaste muscular, también conocido como sarcopenia, disminuye la calidad de vida de la población geriátrica, aumentando la morbilidad y decreciendo la esperanza de vida. Deberían dedicarse más investigaciones al esclarecimiento de los factores/mediadores del proceso caquéctico (asociados a la pérdida de las reservas grasas y de tejido muscular tanto en caquexia como en sarcopenia, ya que podría ser una buena estrategia terapéutica para la prevención y el tratamiento de la pérdida de masa muscular tanto en la enfermedad como durante el envejecimiento sano.Muscle wasting during cancer and ageing share many common metabolic pathways and mediators. Due to the size of the population involved, both cancer cachexia and ageing sarcopenia may represent targets for future promising clinical investigations. Cancer cachexia is a syndrome characterized by a marked weight loss, anorexia, asthenia and anemia. In fact, many patients who die with advanced cancer suffer from cachexia. The degree of cachexia is inversely correlated with the survival time of the patient and it always implies a poor prognosis. In recent years, age-related diseases and disabilities

  16. Study of PDTC on Muscle Wasting of Cancer Cachexia%PDTC调控癌性恶病质肌肉萎缩的实验研究

    Institute of Scientific and Technical Information of China (English)

    佴永军; 江志伟; 姚平; 黎介寿

    2013-01-01

    Objective: To investigate the effect of pyrrolidine dithiocarbamate (PDTC) on muscle atrophy of C26 cachectic mice. Methods: Male BALB/c mice bearing C26 adenocarcinoma were severed as cancer cachexia model. Saline and three doses of PDTC (10, 50 or 100 mg/kg) were given intraperitoneally from the 7th day after tumor inoculation to sacrifice. In the 16th day, the mice were killed, and the body weight, non-tumor body weight, gastrocnemius weight, activity of NF-KB in tumor tissue, and IL-6 levels of serum and tumor tissue were measured. Results: Significantly reduce of non-tumor body weight and gastrocnemius decomposition were observed in all tumor-bearing mice (P<0.01). Furthermore, Tumor-bearing caused a significant increase of IL-6 (P<0.01) in serum and tumor tissues. Administration of PDTC significantly inhibited the NF-KB activation in tumor tissues, inhibited IL-6 synthesis of the tumor cells, and attenuated the non-tumor body weight and gastrocnemius muscle. There was negative correlation between IL-6 level and gastrocnemius muscle weight (r=-0.87, P<0.01). Conclusion: PDTC can improve muscle wasting of cancer cachexia through inhibition of NF-KB activation and IL-6 synthesis.%目的:本研究旨在评价吡咯烷二硫代氨基甲酸盐(PDTC)对C26癌性恶病质小鼠肌肉萎缩的调控作用.方法:采用雄性BALB/c小鼠皮下接种C26结肠癌细胞诱导癌性恶病质模型,荷瘤鼠自第7天开始每日腹腔注射生理盐水及PDTC(10、50及100 mg/kg),第16天处死小鼠后测量体重、去瘤体重及腓肠肌重量,检测肿瘤组织NF-KB活性,血清及肿瘤组织IL-6水平.结果:荷瘤对照组出现显著的去瘤体重下降及腓肠肌分解(P<0.01),血清及肿瘤组织IL-6水平显著升高(P<0.01).PDTC能够显著抑制肿瘤组织NF-kB的激活,从而抑制了肿瘤组织IL-6的合成,其抑制程度与PDTC剂量相关,同时抑制了去瘤体重、腓肠肌的消耗,且腓肠肌重量与血清IL-6

  17. 生脉注射液对癌性恶液质的治疗作用%Effect of Shengmai Injections in Cancer Cachexia

    Institute of Scientific and Technical Information of China (English)

    孙根林; 徐小军; 王浩森; 游善喜

    2016-01-01

    Objective: To explore the effect of Shengmai injections and its possible mechanism in treat-ment of cancer cachexia. Methods: Sixty-four patients were randomly divided into two groups namely the control group and the Shengmai group. Assessments were respectively done before and after treatment in-cluding weight, fatigue, appetite, hemoglobin and depression; TNF-α, IL-6, VEGF and CRP in serum were tested by ELISA. Results: Gender, age, and tumor type and stage between the two groups were comparable (P>0.05). The concentrations of TNF-α, VEGF, IL-6 and CRP between the two groups were similar before treatment (P>0.05) but different after treatment (P0.05,两组治疗前相比TNF-α、VEGF、IL-6、CRP浓度无显著差异,均P>0.05,而两组治疗后相比有显著差异,均P<0.05;治疗后两组恶液质症状及生活质量的改善程度有显著差异,均P<0.05。结论:生脉注射液对诸炎性因子产生作用,起到抗炎作用和下调VEGF表达,从而改善恶液质患者体重减轻、疲劳、食欲减退、贫血、抑郁等症状,提高了生活质量。

  18. Guipi decoction combined with clinical observation of moxibustion for treatment of cancer cachexia%归脾汤加减配合艾灸治疗癌性恶病质的临床观察

    Institute of Scientific and Technical Information of China (English)

    孙素芹; 高磊; 常丽

    2014-01-01

    To observe the clinical therapeutic effect of Guipi Decoction Combined with moxibustion for treatment of cancer cachexia .Methods:All the 30 patients with Guipi Decoction Combined with moxibustion ,and observing the recent curative effect .Results:Some clinical symptoms relieved or disappeared , The majority of the patients appetite improved .Conclusion:Guipi Decoction Combined with moxibustion for treatment of cancer cachexia could receive good clinical results .%目的:观察归脾汤加减配合艾灸治疗癌性恶病质的临床疗效。方法:30例患者均用归脾汤加减内服,同时配合艾灸,观察近期疗效。结果:患者的临床症状部分缓解或消失,多数患者食欲得到改善。结论:归脾汤加减配合艾灸治疗癌性恶病质收到较好的临床效果。

  19. 大肠癌恶病质中医证型与影响因素的相关性研究%Study on Correlativity between TCM Syndrome Types and Influence Factors in Colorectal Cancer Cachexia

    Institute of Scientific and Technical Information of China (English)

    刘丽坤; 王晞星; 李宜放; 何院生; 郝淑兰

    2013-01-01

    目的:初步探讨大肠癌恶病质中医辨证分型与影响因素的关系,为中医辨证论治大肠癌恶病质提供客观科学的依据.方法:通过制订回顾性临床观察表,收集符合纳入标准的病历资料共106例;将患者的各项临床指标作为变量输入计算机,用SAS 9.0软件建立SAS数据库.对所有患者的症状、舌、脉进行聚类分析,根据聚类中心将其分为6类;用因子分析方法,提取大肠癌恶病质常见的中医证候辨证要点,并初步明确证候辨证要点与症状间的关系;用相关分析的方法,观察大肠癌恶病质中医证型与营养不良程度、体重等的相关性.结果:大肠癌恶病质常见6个证候分型:脾虚气滞证、气血两虚证、气阴两虚证、脾虚湿阻证、肠腑不通证、脾胃虚寒证.中医证候分型与病程、KPS、白蛋白等影响因素相关.%Objective:Preliminary study of colorectal cancer cachexia syndrome differentiation of the influencing factors and the relationship between the TCM type syndromes for colorectal cancer cachexia provides an objective scientific basis.Methods:Looking back through the development of clinical observation form,a total of 106 cases met the standard were collected.The patients' clinical indicators were as variables and entered into the computer,with the establishment of database by SAS software SAS 9.0.All the symptoms,tongue,pulse were made the cluster analysis,and according to its cluster center they were divided into 6 categories.By using factor analysis method,colorectal cancer cachexia common TCM syndromes points were extracted,and the relationship between specific syndromes and symptoms was understood.By using the method of correlation analysis,observation of colorectal cancer cachexia TCM type syndromes and levels of malnutrition,weight were carried on.Results:Colorectal cancer cachexia has six syndrome types:spleen deficiency and Qi stagnaition,blood and Qi deficiency,Qi-Yin deficiency

  20. PPARα、PPARγ在左卡尼汀改善结肠癌小鼠恶病质中的作用%L-carnitine Ameliorates Colonic Cancer Cachexia in Mice by Regulating the Expressions of PPARα and PPARγ

    Institute of Scientific and Technical Information of China (English)

    张祎; 易苏红; 蒋芳; 仇月华; 陈汉章; 刘苏; 朱樑

    2013-01-01

    Background: The role of L-carnitine ( LC ) in ameliorating cachexia has been focused on increasingly in recent years. Aims: To investigate the role of PPARα, PPARγ in ameliorating colonic cancer cachexia by LC in mice. Methods: Colonic cancer cachexia model was established in mice. Mice were randomly divided into tumor bearing group treated with LC ( LC group ), tumor bearing group treated with LC palmitoyl-transferase ( CPT ) inhibitor ( ILC group ), tumor bearing group treated with normal saline ( NST group ), and non-tumor bearing mice were served as normal controls ( NTB group ). On the 19th day, all the mice were sacrificed. Body weight, tumor-free body weight, food consumption were measured. Serum levels of albumin, glucose, cholesterol were determined by automatic biochemistry analyzer. ELISA assay was used to detect serum levels of TNF-α and IL-6. mRNA and protein expressions of PPARa, PPARγ in liver tissue were determined by real time quantitive PCR and Western blotting, respectively. Results: Compared with NST group and ILC group, body weight, tumor-free body weight, food consumption, serum levels of albumin and glucose in LC group were significantly increased ( P < 0. 05 ), serum levels of cholesterol, TNF-α, IL-6 were significantly decreased ( P < 0. 05 ), mRNA and protein expressions of PPARa, PPAR-γ were significantly increased ( P < 0. 05 ). Conclusions: PPARa, PPARγ may be involved in the formation of colonic cancer cachexia in mice. The ameliorating of cancer cachexia by LC may be related to the regulating of PPARa-, PPARγ-related signaling pathway of hepatic lipid metabolism.%背景:左卡尼汀(LC)改善恶病质的作用已日渐受到关注.目的:探讨PPARα、PPARγ在LC改善结肠癌小鼠恶病质中的作用.方法:建立结肠癌小鼠恶病质模型,并分为LC组、左卡尼汀棕榈酸酰基转移酶(CPT)抑制剂(ILC)组、阴性对照组(NST),另设立正常对照组(NTB).实验第19 d处死所有小鼠.测定小鼠体质

  1. Carfilzomib联合Z-VAD-FMK对肿瘤恶病质的防治作用%Effects of combination of carfilzomib and Z-VAD-FMK on prevention and treatment of in mice of cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    王强; 李春红; 王朝义; 唐华

    2014-01-01

    Objective To investigate the effects of combination of carfilzomib and Caspase inhibitor Z-VAD-FMK on the prevention and treatment of cancer cachexia and its mechanism.Methods Murine colon adenocarcinoma cells (C26 cells) were subcutaneously injected into male BALB/c mice to induce cancer cachexia model (with typical cachexia signs and symptoms).Then carfilzomib and Z-VAD-FMK in combination or alone were given at different time points.Body weight,tumor mass and volume,gastrocnemius muscle mass,spontaneous activity and survival time were detected.The mRNA and protein levels of Caspase 3,MuRF1 and MAFbx were detected with qRT-PCR and Western blotting,respectively.Results The combination of carfilzomib with Z-VAD-FMK could ameliorate weight loss in tumor-bearing mice,inhibit skeletal muscle atrophy and the growth of tumor,improve the spontaneous physiological activity,prolong the survival time and reduce the expression of MuRF1,MAFbx,and Caspase 3 in gastrocnemius muscle,showing better effects than carfilzomib or Z-VAD-FMK alone (P < 0.05).The effects of prevention were better than that of treatment (P <0.05).Conclusion Ubiquitin-proteasome pathway and apoptosis pathway are inhibited by the combination of carfilzomib and Z-VAD-FMK in cancer cachexia mice,indicating that the combination can prevent and treat the development of cancer cachexia.%目的 评价联合运用蛋白酶体抑制剂Carfilzomib与Caspase抑制剂Z-VAD-FMK对肿瘤恶病质的防治作用及其机制.方法 BALB/c小鼠前腋皮下接种结肠腺癌C26细胞,建立肿瘤恶病质动物模型.随后在不同时间点给予Carfilzomib和Z-VAD-FMK单独与联合用药,检测荷瘤小鼠体质量、腓肠肌质量、肿瘤质量和体积、自发性生理活动和生存时间;qRT-PCR和Western blot检测腓肠肌Caspase3、MuRF1和MAFbx的mRNA表达水平和蛋白水平.结果 Carfilzomib与Z-VAD-FMK联合作用缓解荷瘤小鼠体质量下降,抑制骨骼肌萎缩和肿瘤生长,提高自发性

  2. 锌-α2-糖蛋白与胃肠癌及恶病质的相关性研究%Correlation between zinc-α2-glycoprotein and gastrointestinal cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    黄钟琳; 张波; 吴国豪

    2012-01-01

    Objective Our study aims to analyze the association between zinc-(x2-glycoprotein (ZAG) and cachexia from gastrointestinal cancer by comparing the expression of ZAG between patients with gastrointestinal cancer and without and between patients with cachexia and without. We study the main source of ZAG by analyzing the correlation between ZAG in different tissues and that in body fluids. Methods From Apr to Oct 2009, 120 patients in the department of general surgery of Zhongshan Hospital were recruited and divided into three groups, including cancer cachexia group (rs=40), non-cachexia group (n=40) and control group(n=40). Serum, urine, abdominal subcutaneous fat tissues and tumor tissues were collected. ZAG in these samples were quantitatively detected by ELISA. The expressions of ZAG protein in fat and tumor tissues were determined by Western blot. Results ZAG in serum and urine from patients with gastrointestinal cancer were 152.2 μg/mL and 158.3 μg/mL, which were significantly higher than those from control group (27.1 μg/mL and 26.1 μg/mL, respectively), P<0.001. The patients with cachexia had higher ZAG in serum, urine and tumor tissue than those without cachexia, P=0.010, P=0.022, P=0.005, respectively. ZAG in serum and urine was significantly correlated with that in tumor tissues (r= 0.735, r=0.676), while correlated with that in fat tissue (t-0.457, r=0.534). The expression of ZAG protein in gastrointestinal cancer patients was significantly higher than that in control group, both in tumor and fat tissue. The expression of ZAG in tumor tissues from patients with cachexia was markedly higher than that from patients without cachexia and the difference was slight in fat tissue. Conclusions Theexpression of ZAG was elevated in patients with gastrointestinal cancer, and even more elevation was observed in patients with cachexia. ZAG expression strongly correlated with gastrointestinal cancer and cachexia. The stronger correlation between body fluids with

  3. 白细胞介素10基因多态性与胃癌恶病质的关系%Association of interlenkin-10 gene polymorphism with cachexia in patients with gastric cancer

    Institute of Scientific and Technical Information of China (English)

    孙风波; 张佃良; 郑红梅; 宋波

    2010-01-01

    Objective To investigate whether the single nucleofide polymorphisms (SNPs) at -1082, -819 and -592 of interleukin-10 gene and its haplotype are associated with cachexia in patients with gastric cancer. Methods Radioimmunoassay was used to examine the serum levels of IL-10 in 223 patients with gastric cancer. The single nucleotide polymorphisms (SNPs) of IL-10 gene -1082G/A,-819T/C and -592A/C were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The serum levels of IL-10 were significantly higher in patients with cachexia than those without (P <0.001 ). An increased frequency of - 1082G allele was noted in patients with cachexia (P = 0. 049). The frequencies of -1082AG and -819CC genotypes were elevated in patients with cachexia than those without (P = 0.036, 0.024). In a logistic regression analysis adjusted for actual weight, carcinoma location and stage, the - 1082AG genotype was associated with an odds ratio of 1. 989 (95%CI, 1.041-3.802, P=0.037), and the -819CC genotype with an odds ratio of 3.393 (95% CI,1. 298-8.871, P= 0. 013 ) for cachexia. Furthermore, haplotype analysis revealed that G1082C819C592 haplotype was associated with a significantly increased risk of cachexia ( OR = 2.21; 95% CI, 1.14-4. 30;P =0.02). Conclusion Our results suggest that the gene haplotype of IL-10 contributes to the occurrence of cachexia in patients with gastric cancer in Chinese population.%目的 探讨白细胞介素10(IL-10)基因启动子区-1082、-819和-592位点的多态性及单体型与胃癌恶病质的关系.方法 将223例胃癌患者分为恶病质组107例,非恶病质组116例.用放射免疫学方法检测两组患者的血清IL-10水平,用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测两组患者IL-10基因-1082、-819和-592位点的单核苷酸多态性.结果 恶病质组血清IL-10水平为(91.64±13.25)ng/ml,较非恶病质组[(56.53±12.43)ng/ml]显著升高(P<0

  4. Effect of Cachexia and Bacterial Translocation on Locally Advanced Gastric Cancer%恶液质与肠道细菌移位对局限型进展期胃癌患者临床结局的影响

    Institute of Scientific and Technical Information of China (English)

    王永红

    2014-01-01

    Objective To investigate the relationship between bacterial translocation and gastric cancer patients with ca -chexia.Methods 120 patients with locally advanced gastric cancer were divided into patients with cachexia (group A,60 cases) and patients without cachexia (group B,60 cases).Then the patients were divided into cachexia bacterial translocation positive group(group C),cachexia bacterial translocation negative group (group D),non-cachexia bacterial translocation positive group (group E)and non-cachexia bacterial translocation negative group (group F)according to the result of cultured peripheral blood . 60 healthy volunteers were the control group (group G).The intestinal bacteria were cultivated by peripheral blood;serum tumor necrosis factor α(TNF-α),and interleukin 1(IL-1)were tested;and the 2-year survival rate was calculated .Results ①The bac-terial translocation incidence rates of group A and group B were 26.67% and 6.67%;the bacterial culture results of group G were negative.The bacterial translocation rate in group A was significantly higher than that of group B (P<0.05).②The TNF-αand IL-1αlevel in group C were significantly higher than those of group D ,E,F and G(P<0.05).③The 2-year survival rates in group C,D,E,and F were 12.50%,22.73%, 50.00%,and 46.43%.Conclusion Intestinal bacterial translocation plays an important part in the occurrence and development of cachexia in gastric cancer .%目的:探讨肠道细菌移位与胃癌恶液质患者的关系。方法选择原发性局限型进展期胃癌患者120例,根据有无恶液质表现分为胃癌恶液质组( A组,60例)和胃癌无恶液质组( B组,60例)。外周血培养后,根据结果再分为恶液质细菌移位阳性组(C组)、恶液质细菌移位阴性组(D组),非恶液质细菌移位阳性组(E组)及非恶液质细菌移位阴性组( F组)。选择60例健康体检者作为对照组( G组)。外周血培养肠道细菌;检测

  5. ω-3多烯酸乙酯对肿瘤恶病质的影响及其机制%Effect of ω-3 Acid Ethyl Ester on Cancer Cachexia and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    郭丹; 柳欣欣; 刘玉琴; 顾蓓; 徐锡霞

    2012-01-01

    目的 临床上肿瘤恶病质的治疗十分棘手,初步的研究提示ω-3多不饱和脂肪酸本身作为免疫营养素具有改善肿瘤恶病质的功能.本研究应用在心血管疾病中广泛使用的ω-3多烯酸乙酯口服制剂来干预荷瘤小白鼠,探讨其对肿瘤恶病质的改善作用及机制.方法 使用小白鼠结肠癌细胞株C-26皮下注射Balb/c小白鼠,构建荷瘤小白鼠肿瘤恶病质模型,将小白鼠分为3组:对照组(无荷瘤小白鼠组)、荷瘤无干预组和荷瘤ω-3多烯酸乙酯干预组,荷瘤ω-3多烯酸乙酯干预组小白鼠给予ω-3多烯酸乙酯(DHA、EPA>80%)灌胃(2 g·kg-1·d-1,体积<0.1 ml).连续2周记录小白鼠饮食量、体质量及腓肠肌重量等指标,并比较各组肿瘤组织炎性因子IL-1β、IL-6的mRNA表达差异.结果 ω-3多烯酸乙酯干预组相对于荷瘤无干预组可显著改善荷瘤小白鼠的体质量减轻程度,减少瘦肉体(腓肠肌)的丢失,并降低肿瘤组织的炎性因子IL-1β、IL-6 的mRNA表达水平.结论 口服ω-3多烯酸乙酯可以降低组织炎性因子表达,达到改善肿瘤恶病质的作用.%Objective Treatment of cancer cachexia is difficult, and some studies have suggested that as a kind of immune nutrient, to -3 polyunsaturated fatty acids can improve cancer cachexia and is likely to be a very promising treatment of cancer cachexia. In this study, we used ω -3 acid ethyl ester, which is widely used in cardiovascular diseases, to intervene in the tumor - bearing mice to investigate its effect on cancer cachexia as well as its mechanism. Methods Subcutaneous injection of colon cancer cell line ( C - 26 ) was given to Balb/c mice to build tumor cachexia model. Then the mice were divided into three groups: normal control group ( no tumor - bearing mice ), tumor - bearing mice without intervention group and tumor - bearing mice intervened with oral to -3 acid ethyl ester group. The intervened group was fed with ω -3 acid

  6. 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

  7. 参附注射液联合甲羟孕酮治疗肿瘤恶病质的临床观察%Clinical observation of Shenfu injection combined with medroxyprogesterone acetate for the treatment of tumor cachexia

    Institute of Scientific and Technical Information of China (English)

    陈红; 曾恩泉

    2015-01-01

    目的::观察参附注射液联合甲羟孕酮治疗肿瘤恶病质的临床疗效。方法:将57例肿瘤恶病质患者随机分为治疗组与对照组,两组常规给予静脉营养支持治疗及口服甲羟孕酮分散片,同时治疗组加用参附注射液治疗,治疗前和治疗1个疗程后(共4周)评价患者的进食量、体重、KPS评分、血清白蛋白与血红蛋白值。结果:治疗组在治疗后,进食量、KPS 评分、外周血红蛋白值均有所增加,与治疗前及对照组治疗后相比差异有统计学意义(P0.05)。结论:参附注射液治疗联合甲羟孕酮能增进肿瘤恶病质患者食欲,提高KPS 评分,增加血红蛋白量,改善肿瘤恶病质患者的生活质量,疗效优于常规治疗。%Objective:To observe the clinical efficacy of Shenfu injection combined with medroxyprogesteroneacetate ( MPA) for the treatment of tumor cachexia. Methods:57 cases of cancer cachexia patients were randomly divided into treatment group and control group. Except for giving conventional intravenous nutrition therapy and oral medroxyprogesterone tablet in two groups,the treatment group used Shenfu injection treatment. Before and after one course of treatment (4 weeks) the patients’ intake,body weight,KPS score,serum albumin and hemoglobin values were evaluated. Results:In the treatment group after treatment,food intake and KPS score,peripheral he-moglobin values have increased,compared with before and after treatment in the control group,the difference had statistical significance( P0. 05). Conclusion:Shenfu injection combined with MPA can increase appetite,improve KPS score,increase hemoglobin and im-prove the life quality of patients with tumor cachexia,which is superior to conventional therapy.

  8. Caspase-3在小鼠肿瘤恶病质肌肉蛋白消耗中的作用%Effect of Caspase-3 in skeletal muscle protein consumption of cancer cachexia mice

    Institute of Scientific and Technical Information of China (English)

    郑曰勇; 刘红; 李聪; 王强; 唐华

    2014-01-01

    Objective To explore the expression of caspase-3 in skeletal muscle of the mice in the state of cancer, and to elucidate the relationship between Caspase-3 and apoptosis,consumption of skeletal muscle protein in cancer cachexia.Methods 48 male BALB/c mice were randomly divided into cancer cachexia group and control group (n=24).The mice in cancer cachexia group were inoculated with mouse colon 26 adenocarcinoma cells.The body weights of the mice in two groups were detected daily.Eight mice in each group were executed to test the weight of left gastrocnemius, fiber crosscut area, the expression levels of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6),Caspase-3 proteins and the apoptotic rate of gastrocnemius cells on day 8,14,and 20,respectively. Results The mice in cancer cachexia group appeared cachectic symptoms on day 14,the non-tumor body weight was decreased more than 20% of that in control group (P<0.05).Compared with control group at the same time, the mouse body weight,non-tumor body weight,the weight of left gastrocnemius and the fiber crosscut area of the mice in cancer cachexia group were obviously decreased with the prolongation of inoculation time (P<0.05 ), whereas the expression levels of TNF-α,IL-6,Caspase-3 proteins and the apoptotic rate of muscle cells were obviously increased after tumor inoculation (P<0.05).The level of Caspase-3 protein was negatively correlated with the weight of gastrocnemius and fiber crosscut area (r=-0.716,P<0.05;r=-0.694,P<0.05),and the level of Caspase-3 was positively correlated with the levels of TNF-αand IL-6 (r=0.742,P<0.05;r=0.675,P<0.05).Conclusion Caspase-3 may be a key factor in the protein comsumption of skeletal muscle in cancer cachexia.%目的:探讨半胱氨酸天冬氨酸蛋白酶3(Caspase-3)在小鼠肿瘤恶病质状态下骨骼肌中的表达,阐明Caspase-3与细胞凋亡及肿瘤恶病质骨骼肌蛋白消耗的关系。方法:小鼠结肠腺癌 Colon26(CT26)细胞接种BALB

  9. Effect of protease inhibitor MG132 on cancer cachexia%蛋白酶体抑制剂MG132对肿瘤恶病质的改善作用

    Institute of Scientific and Technical Information of China (English)

    张刘平; 陈志雄; 安昌勇; 寇耀; 唐华; 汤为学

    2012-01-01

    Objective To study the role of different MG132 doses in prevention and treatment of cancer cachexia. Methods A mouse cancer cachexia model was induced by inoculating mouse colon cancer 26 cells into male BALB/c mice. Eighty-eight male BALB/c mice were divided into healthy control (HC) group (re =8) , cancer cachexia (CC) group (re = 16) , low concentration MG132 prevention (PL) group (re =8) , moderate MG132 concentration prevention ( PM) group (re = 16) and high MG132 concentration prevention (PH) group (re =8) , low MG132 concentration treatment (TL) group (n =8) , moderate MG132 concentration treatment (TM) group (n =16) and high MG132 concentration treatment ( TH) group (re =8). Their BMI, diet intake and tumor volume were measured daily. Mice in prevention groups and treatment groups were intraperitoneally injected with MG132 (0.01, 0. 1 and 0.5 mg/kg) on days 5 and 12 after inoculation of colon cancer 26 cells. Eight mice in each group were killed on day 19 after inoculation of colon cancer 26 cells and their tumor, left gastrocnemius muscle and epididymis adipose tissue were weighed. Serum levels of glucose (Glu) , triglyceride (TG) , total protein (TP) and albumin (ALB) were measured. The remaining 8 mice in CC group, PM group and TM group received the original treatment till their death and their survival time was recorded. Results The spontaneous activity and non-tumor BMI, the weight of cross-cut gastrocnemius muscle fiber, gastrocnemius muscle and epididymis adipose, and the serum Glu and ALB levels were significantly higher and the survival time was longer whereas the serum TG level was significantly lower in MG132 prevention and treatment groups than in CC group (P <0. 05). The best effect of MG132 on cancer cachexia was observed in PM and TM groups (P <0. 05) . The tumor growth was significantly inhibited in PH group (P <0. 05) . Conclusion MG132 at a moderate dose can rather effectively prevent and improve cancer cachexia, and prolong the survival

  10. Cachexia in digestive system cancer patients and its impact on clinical outcomes%消化系统恶性肿瘤恶病质及其对临床结局的影响

    Institute of Scientific and Technical Information of China (English)

    孙延东; 刘靖正; 蒋奕; 付为高; 韩寓嵩; 庄秋林; 吴国豪

    2014-01-01

    目的 了解消化系统恶性肿瘤住院患者恶病质患病率及其对临床结局的影响.方法 统计2012年1月至2013年12月复旦大学附属中山医院5 118例消化系统恶性肿瘤住院患者的临床资料,进行恶病质调查并对恶病质组和非恶病质组临床结局进行分析比较.结果 消化系统恶性肿瘤住院患者恶病质总体患病率为15.7% (803/5 118),胰腺癌最高为34.0% (89/173).恶病质组与非恶病质组根治性手术切除率分别为67.1% (539/803)与74.5%(3 214/4 315),差异有统计学意义(P =0.000).与非恶病质组相比,恶病质组术后住院时间增加[(11.5±6.2)d比(9.4±4.9)d,P=0.003],术后排气时间延长[(3.4±0.9)d比(3.2±0.8)d,P=0.013],术后进食半流质时间延长[(4.4±1.5)d比(3.9±1.3)d,P=0.002],术后28 d并发症发生率升高[31.3% (169/539)比26.3% (845/3 214),P=0.014],围术期输血率增加[8.9% (48/539)比5.8% (186/3 214),P=0.006].恶病质组术后转入ICU比例高于非恶病质组[24.3% (131/539)比20.0%(646/3 214),P=0.026].恶病质组与非恶病质组再手术率、呼吸机支持率、病死率分别为3.2%(17/539)比1.5% (48/3 214)、8.0% (43/539)比5.7% (184/3 214)、2.4% (13/539)比1.1%(35/3 214),差异均有统计学意义(P值分别为0.006、0.042、0.011).结论 消化系统恶性肿瘤住院患者常存在恶病质,特别是胰腺癌.恶病质为消化系统恶性肿瘤住院患者临床结局的不利因素.%Objective To investigate the cachexia morbidity among hospitalized patients with digestive system cancer and evaluate its impact on clinical outcomes.Method By analyzing the clinical data of 5 118 hospitalized patients with digestive system cancer in Zhongshan Hospital,Fudan University from January 2012 to December 2013,we investigated the cachexia morbidity and compared the clinical outcome between cachectic patients and noncachectic patients.Results The overall cachexia morbidity of hospitalized patients with

  11. Effect of Proton Pump Inhibitors on Cancer Cachexia in Nude Mice Bearing SGC-7901 Gastric Adenocarcinoma%质子泵抑制剂对SGC-7901胃腺癌裸小鼠癌性恶病质的作用

    Institute of Scientific and Technical Information of China (English)

    沈永华; 陈敏; 沈卫东; 黄淑玲; 张丽莉; 邹晓平

    2011-01-01

    背景:癌性恶病质是癌症晚期最重要的并发症之一.质子泵抑制剂(PPIs)目前广泛用于治疗酸相关疾病,有研究显示其对恶性肿瘤细胞具有化疗增敏和诱导凋亡作用.目的:探讨PPIs对裸小鼠癌性恶病质的改善作用及其可能机制.方法:予BALB/c nu/nu裸小鼠皮下注射人胃腺癌细胞株SGC-901建立癌性恶病质模型并予PPIs干预(奥美拉唑治疗组和泮托拉唑治疗组),同时设立不予干预的癌性恶病质组和非荷瘤空白对照组,每组11只裸小鼠.观察各组裸小鼠的一般情况、肿瘤体积以及与癌性恶病质的发生、发展密切相关的血清细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平.结果:两组PPI治疗组裸小鼠体质量下降受抑,摄食、饮水量明显高于癌性恶病质组,血清TNF-α、IL-6水平明显低于癌性恶病质组,差异均有统计学意义(P<0.05),肿瘤体积则与癌性恶病质组无明显差异.结论:PPIs对裸小鼠的癌性恶病质有明显改善作用,其机制可能与改变体内细胞因子水平有关.%Background: Cancer cachexia is one of the most important complications of advanced cancer. It has been reported that proton pump inhibitors (PPIs), currently used in the treatment of acid-related diseases, can increase the sensitivity of cancer cells to cytotoxic agents and induce cancer cell apoptosis. Aims: To investigate the improvement effect of PPIs on cancer cachexia in nude mice and its possible mechanism. Methods: Thirty-three BALB/c nu/nu nude mice were injected with human gastric adenocarcinoma cell line SGC-7901 subcutaneously to induce cancer cachexia, and then randomized to receive omeprazole, pantoprazole or normal saline treatment (Ome-treated group, Pan-treated group, and cancer cachexia group), respectively; 11 nude mice without any intervention served as blank controls. The general condition, tumor volume and the serum levels of two cachexia-associated cytokines, tumor

  12. Survey of cachexia in digestive system cancer patients and its impact on clinical outcomes%消化系统恶性肿瘤患者的恶病质患病率调查及其对临床结局的影响

    Institute of Scientific and Technical Information of China (English)

    孙延东; 张波; 韩寓嵩; 蒋奕; 庄秋林; 龚昱达; 吴国豪

    2014-01-01

    目的:了解消化系统恶性肿瘤住院患者恶病质患病率及其对临床结局的影响。方法统计2012年1月至2013年12月复旦大学附属中山医院5118例消化系统恶性肿瘤住院患者的临床资料,进行恶病质调查并对恶病质组与非恶病质组患者的临床结局进行分析比较。结果消化系统恶性肿瘤住院患者恶病质总体患病率为15.7%(803/5118),胰腺癌恶病质患病率最高为34.0%(89/262),其次为胃癌22.4%(261/1164)、结肠癌21.7%(146/672)和直肠癌20.1%(117/581)。恶病质组与非恶病质组根治性手术切除率分别为67.1%(539/803)和74.5%(3214/4315),两组比较,差异有统计学意义(P<0.05)。与非恶病质组相比,恶病质组根治性手术后住院天数增加[(11.5±6.2) d比(9.4±4.9) d,P<0.05],术后排气时间延长[(3.4±0.9) d比(3.2±0.8) d,P<0.05],术后进食半流质时间延长[(4.4±1.5) d比(3.9±1.3) d,P<0.05],术后28 d并发症发生率升高[31.4%(169/539)比26.3%(845/3214),P<0.05],围手术期输血率增加[8.9%(48/539)比5.8%(186/3214), P<0.05]。根治性手术后,恶病质组术后进入ICU的比例[24.3%(131/539)]高于非恶病质组[20.1%(646/3214)],差异有统计学意义(P<0.05)。恶病质组与非恶病质组根治术后的再手术率[3.2%(17/539)比1.5%(48/3214),P<0.05]、呼吸机支持率[8.0%(43/539)比5.7%(184/3214), P<0.05]和病死率[2.4%(13/539)比1.1%(35/3214),P<0.05]比较,差异均有统计学意义。结论消化系统恶性肿瘤患者恶病质发生率较高。恶病质对消化系统恶性肿瘤住院患者临床结局具有显著的不利影响。%Objective To investigate cachexia in hospitalized patients with digestive system cancer

  13. Natural developing process of the cancer cachexia-inducing C26 colon carcinoma in mice%C26腺癌恶病质动物模型的自然发展过程

    Institute of Scientific and Technical Information of China (English)

    陈思曾; 肖建东; 黄仲阳

    2012-01-01

    Objective To observe the natural developing process of the cancer cachexia-inducing C26 colon carcinoma in mice.Methods The murine colon 26 adenocarcinoma cells was inoculated subcutaneously into BAL B/C mice.On the day O,5,10,15,20,and 25 after inoculation,body weight and gastroenemius muscle with epididymal adipose were documented. Biochemical parameters,serum tumor necrosis factor-α (TNF-α),the expression of nuclear factor-KB (NF-kB) in tumor and expression of ubiquitin proteasome E3 ligase ( Atrogin-1 ) and muscle ring finger protein 1 ( MURF-1 ) genese were valuated.Results Remarkable malnutrition and metabolic disorder occured about 15 days after the tumor inoculation in this model.There was significant difference in the concentrations of serum albumin between tumor-bearing group and healthy control group at the 15th day [(14.44 ±1.12) vs ( 19.80 ±2.45) g/L,P <0.01].The other biochemical indicators,TNF-α,NF-kB,and Atrogin-1 and MuRF-1 had beneficial changes to varying degrees ( P<0.05 ).Conclusion Cancer cachexia development from the inoculated tumour cells to the obvious symptoms is a long process.The serum albumin may serve as an indicator to judge cancer cachexia development.%目的 观察C26腺癌恶病质动物模型的自然发展过程.方法 于BALB/C小鼠接种结肠腺癌Colon26( C26)细胞,在接种后0、5、10、15、20、25 d,记录小鼠腓肠肌、附睾和去瘤体质量,检测生化指标、肿瘤坏死因子-α( TNF-α)和组织核因子-KB(NF-KB)及泛素蛋白酶体的E3连接酶(Arogin)-1和肌肉环状指蛋白(MURF)-1基因的表达.结果 本模型明显的营养不良和代谢紊乱发生在肿瘤接种后15d.荷瘤组F组较空白对照G组:白蛋白浓度分别为(14.44±1.12)、(19.80±2.45) g/L,(P<0.01);其他生化指标:TNF-α和NF-KB及泛素蛋白酶体的激活也有不同程度改善(P<0.05).结论 癌症恶病质从起始发展到出现明显症状是一个较长的过程;血清白蛋白可以作为判

  14. 钙蛋白酶抑制剂、α-硫辛酸单用及联用治疗癌性恶病质%Caplain inhibitor and α-lipoic acid used alone or in combination for cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    陈思曾; 曹少祥

    2013-01-01

    目的 探讨钙蛋白酶(caplain)抑制剂ALLN(N-acetyl-Leu-Leu-Norleucinal)、α-硫辛酸(α-LA)单用及联用对癌性恶病质小鼠的治疗效果及其机制.方法 结肠腺癌Colon26 (C26)细胞接种于小鼠前腋窝皮下构建恶病质模型.药物干预7d后检测去瘤体质量、腓肠肌湿重、血生化、细胞因子水平、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、肿瘤组织核因子-κB(NF-κB)表达及骨骼肌中caplain-1和泛素mRNA表达.结果 荷瘤对照组caplain-1与泛素mRNA表达值分别为0.84 ±0.10、2.68±0.08,ALLN组、α-LA组、ALLN+ α-LA组caplain-1表达值分别为0.59 ±0.07、0.65±0.07、0.57 ±0.04,泛素mRNA表达值分别为2.29±0.07、2.34 ±0.05、2.20±0.10,均低于荷瘤对照组(P<0.05),其他指标亦有不同程度的改善(P<0.05).结论 caplain抑制剂和α-硫辛酸均具改善癌症恶病质的作用,两者联合应用效果更好.%Objective To study the treatment effects by using calpain inhibitor N-acetyl-Leu-LeuNorleucinal (ALLN) and α-lipoic acid (α-LA) alone or in combination for mice with cancer cachexia and the possible mechanism.Methods Murine colon 26 adenocarcinoma cells were inoculated subcutaneously into the anterior subaxilla of Balb/c mice to establish cachexia modcl.Tumor-free body weight and wet weight of gastrocnemius were measured,and the levels of serum biochemistry parameters,cytokines,malondialdehyde (MAD),superoxide dismutase (SOD),nuclear factor-κB (NF-κB),caplain-1 and ubiquitin mRNA in skeletal muscle were detected at 7th day after intervention.Results The absorbance (A)ratio of calpain-1 and ubiquitin mRNA in tumor-bearing control group was 0.84 ± 0.10 and 2.68 ± 0.08,that of calpain-1 in ALLN group,α-LA group and ALLN + α-LA group was 0.59 ± 0.07,0.65 ± 0.07 and 0.57 ± 0.04,and that of ubiquitin mRNA in ALLN group,α-LA group and ALLN + α-LA group was 2.29 ± 0.07,2.34 ± 0.05 and 2.20 ± 0.10,respectively.The A ratio of calpain-I and

  15. Prevention Measures of PICC Catheter Displacement for Cachexia Patients%防止恶病质患者PICC导管置入过程中移位的方法

    Institute of Scientific and Technical Information of China (English)

    庄海花; 施李娟; 张海燕; 石慧

    2013-01-01

    目的 探讨减少消化系统疾病所致恶病质患者置入三向瓣膜式PICC导管移位至颈内静脉的方法.方法 便利选取2010年1月至2012年7月在长海医院消化科行PICC置管的恶病质患者188例,均为消化系统疾病所致,BMI< 18.5.将188例患者随机分为对照组90例和观察组98例:对照组采取PICC常规置管法,即当导管头端到达肩部后协助患者将下颌靠近穿刺侧肩部,防止导管进入颈内静脉;观察组当导管到达锁骨下静脉中段时,助手在同侧锁骨上窝靠近胸锁关节处以四指并拢向内下方用力按压颈内静脉,防止导管进入颈内静脉.结果 对照组与观察组的置管成功率分别为91.1%(81/90)及97.9%(95/98),差异有统计学意义(x2=5.395,P<0.05).结论 恶病质患者置入PICC过程中,通过指压法可以有效减少PICC置管移位的发生,提高置管的成功率和工作效率.%Objective To study the prevention measures of three-way valve-type PICC catheter displacement to jugular vein for cachexia patients caused by digestive system cancers. Methods From January 2010 to July 2012,188 cachexia patients with digestive system cancers(BMI<18. 5) were randomly divided into control group(n = 90) and experimental group(n = 98). Patients in the control group were assisted to make the submaxillary close to the shoulder on the operation side when the tip of catheter was inserted to this area to prevent the catheter into the internal jugular vein. In the experimental group, the jugular veins of the patients were pressed inward and downward forcefully by the assistant with four fingers putting together at the supraclavicular fossae close to sternoclavicular joint, when the catheter was inserted to prevent the catheter into the internal jugular vein. Results The success rates of PICC catheter in the control group and in the experimental group were 91. 1% (81/90) and 97. 9% (95/98) respectively, and the difference was statistically significant

  16. 胸腺五肽对肿瘤恶病质小鼠免疫调节作用的实验研究%Experimental Study in Immunologic Function of Thymopentin to Cancerous Cachexia of Mice

    Institute of Scientific and Technical Information of China (English)

    刘红; 孙长岗; 杜峰

    2013-01-01

    Objective To discuss the treatment effect of Thymopentin to cancer cachexia on mouse and in -tervention effect of tumor necrosis factor α(TNF-α),interleukin-6(IL-6) and IL-2.Methods Mice bearing colon26 ad-enocarcinoma were served as a model of cancer cachexia .Forty BALB /C mice were divided into control group ,CC group, MPA group and thymopentin-5 group,Body weights,food and water intake were documented .Serum tumor necrosis factorα(TNF-α),interleukin-6(IL-6) and IL-2 levels were evaluated.Results Thymopentin could significantly increase wa -ter and food intake of CC mice,and significantly inhibit the loss of body weight (P <0.05).IL-2 level in Thymopentin group was higher than that in any other group ,and TNF-α,IL-6 level were lower than those in other groups (P <0.05). Conclusion Thymopentin have two-way immune adjustment function,it may potentially moderate cancer cachexia state on mouse,adjust metabolic disorder through up -regulating the serum levels of IL-2 and down-regulating the serum levels of TNF-αand IL-6.%  目的探讨胸腺五肽对小鼠肿瘤恶病质的治疗效果及对肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-2(IL-2)干预的效果.方法利用鼠结肠癌26细胞株皮下接种 BALB /c 小鼠,建立肿瘤恶病质模型. C57BL/6小鼠40只,随机分为正常对照组、肿瘤恶病质(CC)组、甲羟孕酮(MPA)组、胸腺五肽治疗组,检测小鼠体重、摄食、摄水,测量血清 TNF-α,IL-2,IL-6水平.结果胸腺五肽能够明显增加肿瘤恶病质小鼠摄食、摄水量,抑制体重下降(P <0.05),提高恶病质小鼠 IL-2的表达水平,同时降低细胞因子(TNF-α,IL-6)的表达水平(P <0.05).结论胸腺五肽具有双向免疫调节作用,通过降低细胞因子 TNF-α,IL-6水平,升高 IL-2的表达水平,调节代谢紊乱,改善小鼠恶病质状况.

  17. Influence of Shenqi Fuzheng injection on blood lipids in mice with cancer cachexia%参芪扶正注射液对癌症恶病质小鼠血脂的影响

    Institute of Scientific and Technical Information of China (English)

    黄立搜; 王真

    2012-01-01

    [Objective] To observe the effect of Shenqi Fuzheng injection in mice with cancer cachexia and study its mechanism. [Methods] The model of cancer caxhexia was established in CS7 mice and the changes of physiological conditions (body weight, food and water intake) and the levels of triglyceride (TG) and cholesterol (CHOL) were observed. [Results] Shenqi Fuzheng injection could significantly increase water and food intake of mice with cancer cachexia and inhibit the loss of body weight (P<0.05) and the abnormal increasing of TG and CHOL [Conclusion] Shenqi Fuzheng injection can significantly improve the cancer caxhexia in cancer mice, and its mechanism may be related to the inhibition of lipolysis.%[目的]观察参芪扶正注射液对癌症恶病质小鼠恶病质状态的影响,探讨参芪扶正注射液治疗癌症恶病质的作用机制.[方法]建立C57小鼠癌症恶病质模型,观察参芪扶正注射液对恶病质小鼠的一般状况,如体质量、摄食量、饮水量的影响;观察血清中甘油三酯(TG)和胆固醇(CHOL)的水平变化.[结果]参芪扶正注射液能明显增加癌症恶病质小鼠摄食量及饮水量,抑制体质量下降(P<0.05);可显著抑制血清中TG和CHOL的异常升高.[结论]参芪扶正注射液对小鼠的癌症恶病质有明显的改善作用,其作用机制可能与其抑制脂肪分解有关.

  18. Role of zinc-α2-glycoprotein in lipid metabolism in cancer cachexia%锌-α2-糖蛋白在肿瘤恶病质脂肪代谢中的作用

    Institute of Scientific and Technical Information of China (English)

    黄钟琳; 张波; 吴国豪

    2010-01-01

    Zinc-α2-glycoprotein (ZAG), a new adipokine, plays an important role in the development of cancer cachexia by decreasing lipid content in body via promoting lipid mobilization and utilization. The lipolytic effect of ZAG is achieved by increasing the activity of hormone sensitive lipase, activating β3 adrenergic receptors,and up-regulating cyclic adenosine monophosphate. In addition, ZAG increases adiponectin expression and decreases leptin expression in adipocytes and adipose tissue. The ZAG expression is regulated by glucocorticoid, peroxisome proliferator-activated receptor gamma agonist rosiglitazone, tumor necrosis factor-α and many other factors.ZAG can potentially be applied as a tumor marker, and may become a new target in the treatment of cancer cachexia.%锌-α2-糖蛋白(ZAG)是一种新型脂肪细胞因子,主要通过促进脂肪分解和利用来减少体内脂肪含量,在肿瘤恶病质的发生中发挥重要作用.ZAG促进脂肪分解的作用主要是通过增强激素敏感性脂酶活性、激活细胞膜上β3肾上腺素受体,进而上调细胞内环腺苷酸信号转导途径完成的.此外,ZAG能促进脂联素,抑制瘦素在脂肪细胞和脂肪组织中的表达.脂肪细胞中ZAG的表达受糖皮质激素、过氧化物酶体增殖物激活受体γ激动剂罗格列酮、肿瘤坏死因子-α等多种因素的调节.ZAG有作为肿瘤标志物的潜在价值,有望成为肿瘤恶病质治疗新的靶点.

  19. 塞来昔布和谷氨酰胺保护癌性恶病质肠粘膜屏障机制探讨%The protection of cancer cachexia mice from intestinal mucosal injury by Celecoxib

    Institute of Scientific and Technical Information of China (English)

    贾云鹤; 李明琦; 薛伟男; 孙梓程; 王轶慧; 董巍; 王平; 朱磊; 江志伟

    2013-01-01

    目的 探讨塞来昔布和谷氨酰胺保护癌性恶病质小鼠肠粘膜的机制.方法 28只恶病质小鼠模型随机分为四组:荷瘤组、塞来昔布、谷氨酰胺组和塞来昔布联合谷氨酰胺组.评价塞来昔布和谷氨酰胺对恶病质鼠体重变化和小肠粘膜萎缩以及血清和小肠组织炎性细胞因子表达的影响.结果 塞来昔布和谷氨酰胺均具有抑制恶病质鼠体重下降,保护小肠绒毛,抑制血清中TNFα和IL-6升高、增加sTNFRⅠ、IL-10分泌的作用.二者联用能够升高小肠组织中IFN-γ.结论 塞来昔布和谷氨酰胺通过调节血清和小肠组织中的炎性反应因子保护肠粘膜,缓解体重下降.%Objective To discuss the protection mechanism of intestinal mucosal injury by Celecoxib and glutamine of cancer cachexia mice. Methods 28 mice were divided into four groups randomly. The weight loss, the height and width of intestinal villi as well as the thickness of muscular layer and basal layer were compared in these groups. The inflammatory cytokines in the mucous membrane and blood serum were tested. Results The body weight loss and mucous membrane of small intestine atrophy were inhibited by Celecoxib and glutamine. TNF and IL - 6 expressions decreased, and sTNFR Ⅰ and IL - 10 expressions increased in blood serum. INF-γ lerel increased in mucous membrane after treated by the Celecoxib and glutamine. Conclusion Celecoxib and glutamine can protect the weight loss by inhibiting the inflammation in cancer cachexia mice.

  20. Nursing Experience of Comprehensive Nursing Intervention on the Patients with Liver Cancer with Cachexia%综合护理干预对肝癌伴恶液质患者的护理体会

    Institute of Scientific and Technical Information of China (English)

    朱感华; 余朝凤; 郭田

    2016-01-01

    Objective To improve the quality of life, improve the psychological status and prolong the survival time of the patients with liver cancer and the patients with the liquid quality. Methods Selected April 2010 to October 2014 were 83 cases of hepatocellular carcinoma with cachexia in patients with, for liver cancer patients with cachexia in patients with poor quality of life, lose confidence to the life, given specialist care, basic nursing, psychological nursing and nursing of traditional Chinese medicine and comprehensive nursing and to the families of effective management. Results The quality of life of the patients was significantly improved, the life confidence was increased, the family members could cooperate effectively and the quality of nursing was satisfied. Conclusion The comprehensive nursing intervention on the quality of life of patients with liver cancer and the quality of life of the patients with the quality of life of the patients was improved obviously, the mental state was significantly improved and the survival time of the patients was prolonged.%目的:对肝癌伴恶液质的患者实施综合性护理干预以提高患者生存质量,改善心理状态及延长患者生存时间。方法入选我科2010年4月~2014年10月收治的83例肝癌伴恶液质患者,针对肝癌伴恶液质患者生活质量低下、对生活失去信心,予专科护理、基础护理、心理护理及中医护理等综合护理并对家属进行有效管理。结果患者的生活质量明显改善、生活信心增强,家属能有效配合并对护理质量满意。结论综合护理干预对肝癌伴恶液质患者的生活质量明显提高,心理状态明显改善并有效延长患者生存时间。

  1. Changes and significance of serum IL-1 and GH/IGF-1 levels in advanced non-small cell lung cancer patients with cachexia%晚期非小细胞肺癌恶病质患者血清IL-1和GH/IGF-1水平的变化及意义

    Institute of Scientific and Technical Information of China (English)

    何婧; 缪捷飞; 钱俐

    2016-01-01

    目的:观察晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)恶病质患者血清白细胞介素-1(interleukin-1, IL-1)、生长激素(growth hormone, GH)/胰岛素样生长因子-1(insulin-like growth factor 1, IGF-1)水平的变化及其意义。方法:选取41例晚期NSCLC恶病质患者为恶病质组;42例晚期NSCLC非恶病质患者为非恶病质组;另选取24例健康就诊者为对照组。检测所有入选者的营养参数包括体质量指数(body mass index, BMI)、上臂中部臂围(mid-upper arm circumference, MAC)及血清白蛋白(albumin, ALB);并用酶联免疫吸附法检测入选者血清IL-1、GH和IGF-1的含量。结果:(1)与对照组相比,非恶病质组BMI、MAC及ALB的差异无统计学意义(P>0.05),恶病质组BMI、MAC及ALB均明显降低(P<0.05);与非恶病质组相比,恶病质组BMI、MAC及ALB均明显降低(P<0.05)。(2)与对照组相比,非恶病质组及恶病质组血清IL-1、GH及IGH表达均明显增加(P<0.05),恶病质组GH/IGF-1升高(P<0.05);与非恶病质组相比,恶病质组血清IL-1及GH表达增加(P<0.05),而IGF-1表达降低(P<0.05),GH/IGF-1升高(P<0.05)。结论:晚期NSCLC恶病质患者营养状况明显恶化,IL-1和GH/IGF-1的变化可能介导了晚期NSCLC患者恶病质的发生。%Objective:To study the expression of serum interleukin-1(IL-1) and growth hormone/insulin-like growth factor 1 (GH/IGF-1) levels in advanced non-small cell lung cancer(NSCLC) patients with cachexia and its significance. Methods: 41 cases of NSCLC patients with cachexia were used as the cachexia group; 42 cases of NSCLC patients without cachexia were used as the non-cachexia group; and 24 healthy people were taken as normal controls. All the subjects were tested the nutrition index such as:body mass index(BMI), mid-upper arm circumference(MAC) and serum albumin(ALB);and the serum levels of IL-1, GH and IGF-1 were detected by enzyme-linked immunoabsorbent

  2. The Influence of Jianpi Yishen Fang Combined with Megestrol on FAACT of 30 Patients with Digestive Tumor Cachexia%健脾益肾方联合甲地孕酮对消化系肿瘤恶病质30例FAACT的影响

    Institute of Scientific and Technical Information of China (English)

    徐力; 白晶

    2011-01-01

    目的 观察健脾益肾方联合甲地孕酮对消化系肿瘤恶病质30例患者食欲不振恶病质综合征治疗的功能性评价量表(FAACT)的影响,明确中医健脾益肾方在治疗癌症恶病质中的临床价值.方法 采用随机对照的方法,将60例消化系肿瘤恶病质患者,随机分为2组,其中治疗组(健脾益肾方联合甲地孕酮组)30例、对照组(单纯甲地孕酮组)30例.治疗前后分别观察2组FAACT评分.结果 治疗组治疗后见FAACT总分明显提高,对照组治疗后总分也有所提高.2组治疗后比较,差异有统计学意义(P<0.05).结论 健脾益肾方联合甲地孕酮能增加消化系肿瘤恶病质综合征患者的食量,增加体力,改善食欲不振恶病质综合征,提高生活质量,表明癌症恶病质患者加中药治疗具有一定的临床价值.%OBJECTIVE To observe the influence of Jianpi Yishen Fang combined with megestrol on FAACT of anorexic cachexia syndrome of 30 patients with digestive tumor cachexia and to ensure the clinical value of this formula in the treatment of cancer cachexia. METHODS Randome control method was adopted to divide 60 patients with digestive tumor cachexia into two groups, in which 30 cases were in treatment group (Jianpi Yishen Fang combined with megestrol group) and 30 cases were in control group (single megestrol group). FAACT scores of two groups were observed respectively before and after treatment. RESULTS After treatment, the total FAACT score of treatment group improved obviously and the total score of control group was also enhanced. In comparison to both groups after treatment, there was statistical significance (P<0.05). CONCLUSION Jianpi Yishen Fang combined with megestrol can increase the appetite of patients with digestive tumor cachexia syndrome, strengthen their physical force, and improve anorexic cachexia syndrome as well as life quality, suggesting a certain clinical value for patients with cancer cachexia to add the treatment of

  3. Association of cytokine gene polymorphisms with cachexia related to sporadic female breast cancer%细胞因子基因多态性与女性散发性乳腺癌患者癌性恶液质的关系

    Institute of Scientific and Technical Information of China (English)

    李福年; 张佃良; 李云东; 姜桂美

    2008-01-01

    Objective To investigate the relation of the frequency of tumor necrosis factor(TNF)-α-308,TNF-β+252,IL-1 β+3954,and IL-10-1082 gene polymorphisms to female breast cancer.Methods Peripheral blood samples were collected from 102 breast cancer patients with cachexia and 120 breast cancer patients without cachexia.Biallelic polymorphisms were performed by analyzing the incision enzyme-digested DNA fragment obtained using PCR.Results The allele frequencies of TNF-β+252,IL-1β+3954,and IL-10-1082 in the patients with cachexia were comparable with those of the patients without cachexia(all P>0.05).The patients with cachexia showed a significantly higher prevalence of TNF2 than the patients without cachexia(20.6%vs 10.0%,P=0.027).Logistic regression analysis indicated TNF2 as a risk factor for cachexia in breast cancer(OR=2.333,95%CI:1.085-5.017).Conclusion TNF2 plays an important role in the susceptibility ofcachexia in breast cancer.%目的 探讨肿瘤坏死因子(TNF)α-308、TNF-β+252、白细胞介素(IL)1β+3954及IL-10-1082基因单核苷酸多态性与乳腺癌患者癌性恶液质的关系.方法 该研究包括102例乳腺癌合并恶液质患者,对照组为120例乳腺癌不合并恶液质患者.用PCR结合限制性内切酶检测外周血单个核细胞TNF-α-308、TNF-β+252、IL-1β+3954及IL-10-1082基因单核苷酸多态性.结果 TNF-β+252、IL-1β+3954及IL-10-1082基因单核苷酸多态性出现的频率在恶液质组和无恶液质组差异无统计学意义(P>0.05).在恶液质组TNF2出现率显著高于无恶液质组(20.6%vs 10.0%,P=0.027).Logistic回归分析表明,TNF2是影响恶液质的一个危险因素,OR=2.333,95%的可信区间为(1.085~5.017).结论 TNF2与乳腺癌性恶液质的易感性有关.

  4. Combined use of iguratimod with pyrrolidine dithiocarbamate alleviates cancer cachexia in a mouse model%艾拉莫德、吡咯烷二硫代氨基甲酸盐单用和联合治疗恶病质

    Institute of Scientific and Technical Information of China (English)

    陈思曾; 郭永刚

    2011-01-01

    目的 观察艾拉莫德(T614)、吡咯烷二硫代氨基甲酸盐(PDTC)联合应用对小鼠癌症恶病质的治疗作用.方法 于雄性BALB/C小鼠接种小鼠结肠腺癌Colon26(C26)细胞,9 d后恶病质模型基本建立.用药7 d后,记录小鼠左侧腓肠肌重量和去瘤体质量,检测血生化指标、血清白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)水平并用免疫组织化学法检测肿瘤组织核因子-κB(NF-κB)表达.结果 恶病质组小鼠血清IL-6、TNF-α浓度为(93.72 ±11.20)、(128.70±33.41)ng/L.T614组、PDTC组、T614+PDTC组IL-6浓度为(81.11±+11.08)、(79.25±9.91)、(53.60±10.5)ng/L,TNF-α浓度为(90.16±11.57)、(99.51±15.25)、(75.45±12.48)ng/L,均低于恶病质组(P<0.05),各生化指标亦有不同程度的改善(P<0.05).结论 通过抑制NF-κB可以改善恶病质.T614和PDTC联合应用治疗效果优于单种药物.%Objective To observe the effect of the combined use of iguratimod (T614) and pyrrolidine dithiocarbamate (PDTC) on animal cancer cachexia model. Methods Male BALB/C mice bearing colon 26 adenocarcinoma for 9 days served as models of cancer cachexia. Seven days after the treatment,body weight and gastrocnemius muscle were documented. Biochemical indicators, serum interleukin-6 (IL-6) , and tumor necrosis factor-α (TNF-α) levels were evaluated. The expression of nuclear factor-κB ( NF-κB ) in tumor was detected by using immunohistochemistry. Results The IL-6 levels in cachexia group, T614 group, PDTC group and T614 + PDTC group were (93. 72 ± 11. 20), (81.11 ± +11.08),(79. 25 ±9. 91) and (53. 60 ± 10. 5) ng/L, and those of TNF-a were (128. 70 ± 33. 41) , (90. 16 ±11. 57) , (99. 51 ± 15. 25) and (75. 45 ± 12. 48) ng/L, respectively. The IL-6 and TNF-α levels in T614 group, PDTC group and T614 + PDTC group were significantly lower than in cachexia group ( all P <0. 05). The expression of NF-kB was significantly down-regulated in T614 group, PDTC group and T614 +PDTC

  5. Function and molecular mechanism of protease inhibitor MG132 in cancer cachexia%蛋白酶体抑制剂MG132对肿瘤恶病质的作用及其分子机制

    Institute of Scientific and Technical Information of China (English)

    张刘平; 唐华; 寇耀; 郑曰勇; 陈志雄; 安昌勇

    2013-01-01

    Objective To investigate the function and possible molecular mechanism of protease inhibitor MG132 in cancer cachexia. Methods Twenty-four male BALB/c mice were divided into healthy control (HC), cancer cachexia (CC) and MG132 treatment (MG) groups. The mice in HC group were uninjected, while those in CC and MG groups were injected s.c. with colon adenocarcinoma C26 cells to establish the mouse model of cancer cachexia. The model mice in MG group were injected i.p. with 0. 1 mg/kg MG132, while those in CC group with 0. 1 ml physiological saline. The mice in various groups were killed 7 d after treatment, of which the tumor, left gastrocnemius muscle and epididymis adipose tissue were weighed, the fiber crosscut area of gastrocnemius muscle was measured, the TNF-a and IL-6 levels in sera were determined by ELISA, while the mRNA transcription and protein expression levels of IkBa, P65, MuRF1 and MAFbx were determined by RT-PCR and Western blot respectively. Results Compared with those in CC group, the weights of gastrocnemius muscle and epididymis adipose tissue of mice in MG group increased by 31. 6% and 39. 5% respectively(P < 0. 05), the fiber crosscut area of gastrocnemius muscle increased by 36. 1% (P < 0. 05), while the TNF-a and IL-6 levels in sera decreased by 20. 9% and 42. 0% respectively (P < 0. 05); however, the mRNA transcription and protein expression levels of IKBa in gastrocnemius muscle increased by 132. 7% and 56. 5% respectively (P < 0. 05), while those of MuRFl decreased by 70. 1% and 42. 6%(P < 0. 05), those of MAFbx decreased by 76. 8% and 47. 3% (P < 0. 05), and those of P65 decreased by 59. 1% and 53. 1%, respectively (P < 0. 05). Conclusion The molecular mechanism of MG132 in improving cancer cachexia may be related to the inhibitions of NF-KB pathway, MuRFl and MAFbx expressions, inflammatory reaction and tumor growth.%目的 探讨蛋白酶体抑制剂MG132对肿瘤恶病质的作用及其可能的分子机制.方法 经小

  6. 健脾益肾方联合甲地孕酮治疗消化系肿瘤恶病质的临床观察%Clinical Observation on Jianpi Yishen Prescription in Combination With Megestrol in Treatment of Digestive Cancer Cachexia

    Institute of Scientific and Technical Information of China (English)

    陈亮

    2016-01-01

    Objective To study the patients with digestive cancer cachexia, observe the clinical effect of Jianpi Yishen prescription + megestrol after treatment.Methods From September 2013 to September 2015, 70 cases of patients with digestive tumor cachexia were selected. B1 group (observation group of 35 cases) received spleen and kidney party + megestrol, B2 group 35 cases (control group) received megestrol, compared the clinical curative effect.ResultsComparing to B2 group of patients, the FAACT scores in group B1 showed signiifcant advantage (P<0.05).Conclusion For patients with digestive cancer cachexia syndrome, Jianpi Yishen prescription +megestrol can effectively improve the quality of life.%目的:探讨消化系肿瘤恶病质患者,观察选择健脾益肾方+甲地孕酮完成治疗后获得的临床效果。方法选择2013年9月~2015年9月消化系肿瘤恶病质患者70例。通过抽签法完成分组。B1组(观察组35例):健脾益肾方+甲地孕酮;B2组(对照组35例):甲地孕酮,比较临床疗效。结果同B2组患者进行比较,B1组FAACT总分表现出优势(P<0.05)。结论针对消化系肿瘤恶病质综合症患者,临床选择健脾益肾方+甲地孕酮进行治疗,有效提高生活质量。

  7. Ghrelin and Ghrelin mimetics in cancer-related anorexia and cachexia syndrome%Ghrelin及其类似物与肿瘤厌食恶液质综合征治疗

    Institute of Scientific and Technical Information of China (English)

    王琳

    2015-01-01

    目的:肿瘤厌食恶液质综合征是恶性肿瘤临床诊疗常见的复杂综合征,在晚期阶段伴有较高的死亡率,近年来, Ghrelin及类似物治疗肿瘤恶液质研究进展较大,显示良好的疗效及耐受性,本文就Ghrelin及其类似物和相关激素在肿瘤厌食恶液质综合征中的研究现状及进展作一文献综述。方法以“肿瘤恶液质、Ghrelin、Ghrelin类似物、生长激素、胰岛素、胰岛素生长因子1”作为关键词检索中文及外文数据库,如CNKI,Pubmed等。结果阿拉莫林等Ghrelin类似物及增敏剂增加肿瘤恶液质患者瘦体组织,改善症状及生活质量,不促进肿瘤生长。胰岛素、胰岛素生长因子1、生长激素没有确凿证据可使肿瘤恶液质治疗获益。结论在肿瘤恶液质实验研究中,以阿拉莫林为代表的Ghrelin类似物及增敏剂疗效显著,具备良好的临床应用前景。%ObjectiveCancer-related anorexia and cachexia syndrome (CACS) is a kind of complex clinical syndrome with a high mortality in advanced stage of cancer. Ghrelin and Ghrelin mimetics have showed excellent effect and tolerance in latest studies. In this paper, we review the present situation and the progress in studies about the effect of Ghrelin, Ghrelin mimetics and related growth factors in CACS.Methods Related articles were obtained through comprehensive search in the database, like CNKI, Pubmed, and so on, with the keywords “cancer, cachexia, Ghrelin, Ghrelin mimetics, growth hormone, insulin, insulin-like growth factor-1”.Results Ghrelin mimetics, like Anamorelin consistently increased lean body mass, improved symptoms and quality of life, and have not shown an increase in tumor proliferation in CACS. There were no substantial evidence to support that growth hormone, insulin and insulin-like growth factor-1 would beneift patients with CACS.Conclusions Ghrelin mimetics and potentiation of ghrelin, represented by Anamorelin have

  8. 吉西他滨致轻度胰腺癌相关恶病质模型的建立%Establishment of Gemcitabine-induced mild cachexia model with pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    吴建华; 贾林; 江舒曼

    2012-01-01

    目的 探讨吉西他滨致胰腺癌轻度恶病质模型的制备方法.方法 24只裸鼠胰腺癌皮下移植瘤模型随机平均分为G0组、G3组(吉西他滨50 mg/kg,腹腔内给药,术后第1、4、7天)、G4组(吉西他滨50 mg/kg,腹腔内给药,术后第1、4、7、10天),实验共25 d.比较3组动物体质量、进食量、肿瘤体积、皮下脂肪及臂围的变化及其时-效关系.结果 G3组和G4组与G0组在体质量、进食量、肿瘤体积、皮下脂肪及臂围方面,比较差异均有统计学意义(P<0.05).第13天时,G3组与G4组动物的平均体质量下降分别为9.7%、14.1%;第14天时,G4组的日均进食量[(3.38±0.14)g]显著低于G3组[(3.59±0.12)g,P<0.05].结论 不同剂量的吉西他滨对裸鼠胰腺癌模型的进食和体质量具有显著影响,其中吉西他滨(50 mg/kg,腹腔内给药,术后第1、4、7天)为制备轻度胰腺癌相关恶病质模型的适宜剂量.%Objective To investigate the establishment of mild cachexia model by using Gemcitabine in pancreatic tumor-bearing mice. Methods 24 xenograft nude mice were randomly divided into GO group,G3 group(given 50 mg/kg of Gemcitabine intraper-itoneal on days 1,4,7 after transplantation) and G4 group(given 50 mg/kg of Gemcitabine intraperitoneal on days 1,4,7,10 after transplantation) by average. Body weight,food intake,tumor size,subcutaneous fat,arm circumference and the time-effect relationship were compared among the three groups. Results There were significant differences in body weight, food intake, tumor size, subcutaneous fat and arm circumference between chemotherapy groups and control group(P<0. 05). At 13 d,the weight loss of G3 and G4 groups were 9. 7% and 14. 1% respectively. At 14 d,the food intake of G3 gruop[(3. 59 ± 0. 12)g] was significantly higher than that of G4 gruop[(3. 38 ± 0. 14)g,P<0. 05]. Conclusion Different doses of Gemcitabine had a significant impact on the body weight and food intake of the xenograft nude mice with

  9. 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.

  10. 104例晚期肿瘤恶液质患者营养治疗临床分析%Clinical Analysis of Nutrient Fluid Treatment on 104 Cases of Patients of Advanced Cancer Malignant Cachexia

    Institute of Scientific and Technical Information of China (English)

    陈显荣

    2015-01-01

    Objective To explore the clinical effect of providing patients of tumor cachexia ( TC) with assisted treatment of nutritional regulation .Methods Randomly selected 104 diagnosed hospital TC patients who were given parenteral treatment for 1 weeks , observed and evaluated the ECOG score ( phys-ical status score ) , the change and the adverse reactions before and after the treatment .Results The av-erage ECOG score of patients was (3.5 ±1.8) before assisted treatment of nutritional regulation and (2.2 ±1.1) after.The ECOG store was significantly lower after the assisted treatment of nutritional regu -lation than before ( P<0.05 ) and no serious negative reaction occurred .Conclusion Assisted treat-ment of nutritional regulation on TC patients can improve the self-care ability and the quality of life of pa-tients.This treatment is safe and with fewer adverse effect , therefore suitable for clinical application .%目的:探讨晚期肿瘤恶液质患者给予营养调节辅助支持治疗( NT)的临床疗效。方法随机选取住院治疗确诊晚期肿瘤恶液质患者104人,给予肠外治疗1周,观察和评价患者治疗前后ECOG评分(体力状况评分),变化和发生不良反应情况。结果给予营养支持治疗前,患者ECOG评价为3.5±1.8,实施NT后为2.2±1.1,较NT前明显降低(P<0.05),未见较严重的副反应发生。结论对晚期肿瘤恶液质患者实施营养支持治疗可以改善患者自理能力,提高生活质量,安全性好,副反应少,适宜于临床应用。

  11. 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

  12. 局部热疗联合最佳支持治疗改善消化系统肿瘤恶病质临床观察%Clinical observation of local hypeythermia combined with best support treatments on cancer cachexia of digestive tract

    Institute of Scientific and Technical Information of China (English)

    亓久德; 郭本成

    2013-01-01

    目的 观察局部热疗联合最佳支持治疗改善消化系统肿瘤患者恶病质的有效性,为晚期肿瘤患者恶病质的姑息治疗提供有价值的临床数据.方法 58例消化系统癌性恶病质患者随机分为对照组和治疗组,对照组仅行最佳支持治疗;治疗组同时接受局部热疗治疗.进行1月前、后两组主观综合性营养评价(SGA)及实验室检查(血清白蛋白、前白蛋白、淋巴细胞总数).结果 SGA评估结果两组比较差异有统计学意义(P<0.01).治疗组治疗前、后血清白蛋白、前白蛋白、淋巴细胞总数比较差异均有统计学意义(P<0.01).结论 局部热疗治疗改变了消化系统肿瘤患者恶病质的预后,有利于遏制恶病质的进展.%Objective To investigate the effect of local hypeythermia combined with best support treatments ( BSC) on cancer cachexia of digestive tract and to offer value clinical data for palliative treatments of patients with advanced malignant tumor. Methods Fifty-eight patients with cancer cachexia of digestive tract were randomly divided into two groups, the patients in the study group ( n = 30) were given local hypeythermia plus BSC,and the patients in the control group(n =28) were given BSC alone. The subjective global assessment of nutritional status (SGA) and lab examnations ( ALB, pre-ALB and TLC) after 1 month were evaluated. Results The evaluation of the SGA and ALB, pre-ALB and TLC in both groups had significant difference ( P < 0. 01 ). Conclusion Local hypeythermia can change the prognosis and prohibit the progressing of cancer cachexia.

  13. 米氮平改善消化道肿瘤恶液质食欲和营养状况的初步研究%Preliminary study of the effect of Mirtazapine in improving appetite and nutritional status in patients with digestive cancer related cachexia

    Institute of Scientific and Technical Information of China (English)

    谢飚; 贾林; 平丽; 吴琼

    2013-01-01

    Objective To observe the effect of mirtazapine in improving the appetite and nutritional status in patients with digestive cancer related cachexia and its mechanism. Methods:82 patients with digestive cancer related cachexia were divided into two groups: the treatment group(n=52) was treat with Mirtazapine and the control group(n=30) was treat with placbo. The appetite,body weight, Karnofsky score, BMI, TSF, MAC and level of serum leptin in two groups were compared. Results:The appetite, body weight and Karnofsky score were obviously improved after Mirtazapine treatment in the treatment groups patients; The level of BMI、TSF、MAC and serum leptin were increased in same groups. The difference between two groups was significant(P<0.05). Conclusion: Mirtazapine can improve the appetite and nutritional status in patients with digestive cancer related cachexia.Leptin maybe involved in the process.%目的:观察米氮平改善消化道肿瘤恶液质患者食欲和营养状态的疗效及可能机制。方法:82例消化道肿瘤恶液质患者,随机分为治疗组(n=52),对照组(n=30),治疗组给予米氮平口服1月,对照组给予安慰剂。观察两组食欲、体重、Karnofsky评分、BMI、TSF、MAC及血浆瘦素水平在治疗前后的变化。结果:米氮平组患者治疗后食欲改善,体重增加,Karnofsky评分增加,BMI、TSF、MAC及血浆瘦素升高,和对照组比较有显著性差异(p<0.05)。结论:米氮平改善消化道肿瘤恶液质患者的食欲及营养状态有较好疗效,瘦素可能参与了其作用过程。

  14. 四君子汤对肺癌恶病质小鼠骨骼肌萎缩及部分炎症细胞因子的影响%Effect of Sijunzi Decoction on Skeletal Muscle Atrophy and Some Inflammatory Cytokines in Lung Cancer Cachexia Mice

    Institute of Scientific and Technical Information of China (English)

    梁芳; 李朝衡; 孙珏; 郭刚; 隋华; 曹海涛

    2012-01-01

    Objective: To observe the effect of Sijunzi Decoction on skeletal muscle atrophy in lung cancer cachexia mice, and to discuss the mechanism from inflammatory cytokines. Methods :To establish mice model of cancer cachexia by inoculating lewis lung cancer cell lines to C57B1/6 mire subcutaneously. 60 mice were randomly divided into 6 groups. The tumor weight and gas-trocnemius muscle weight were monitored, and the serum tumor necrosis factor - α (TNF - α ) and interleukin - 6 (IL - 6 ) levels were measured. Results :The weight of gastrocnemius muscle were significantly decreased in the mice (P < 0, 05 ) , serum TNF - a and IL-6 levels were significantly increased(P<0. 05). In treated groups,the weight reduction of gastrocnemius in cachexia mice and the serum levels reduction of TNF -α and IL -6 were slight. Conclusion:Sijunzi Decoction could slowdown the cancer cachexia of skeletal muscle atrophy,and its mechanism may be associated with the decreasing expression of inflammatory cytokines.%目的:观察四君子汤对肺癌恶病质小鼠骨骼肌萎缩的影响,并从炎性细胞因子的角度对其部分作用机制进行探讨.方法:利用lewis肺癌细胞株皮下接种C57B1/6小鼠,建立肺癌恶病质小鼠模型.将60只小鼠随机分为6组,荷瘤中药长期大剂量组,荷瘤中药短期大剂量组,荷瘤中药长期小剂量组,荷瘤中药短期小剂量组,荷瘤空白组,生理盐水对照组监测各组小鼠的去瘤体重和腓肠肌重量,测量血清TNF-α和IL-6水平.结果:肺癌恶病质小鼠腓肠肌重量明显下降(P<0.05),血清TNF-α和IL-6水平明显升高(P<0.05),治疗组可以不同程度地缓解恶病质小鼠腓肠肌重量的下降,其中以长期大剂量组效果最优(P<0.05).结论:四君子汤能够减缓肺癌恶病质小鼠骨骼肌萎缩的发生程度,其作用机制可能与减少部分炎性细胞因子的表达有关.

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

    Directory of Open Access Journals (Sweden)

    P. P. García-Luna

    2006-05-01

    Full Text Available 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 absorción de nutrientes. • Aumento de las necesidades. • Alteraciones en el Metabolismo de los nutrientes. El tratamiento oncológico, en cualquiera de sus vertientes induce la aparición de desnutrición, sobre todo en aquellos casos en que se administran varios tratamientos para la curación del cáncer (cirugía, radioterapia y quimioterapia. La desnutrición en el paciente neoplásico produce una disminución de masa muscular que conlleva una pérdida de fuerza que tiene importantes consecuencias sobre el estado funcional del individuo, pues aumenta la dependencia de cuidados por terceros (familiares o cuidadores y disminuye su calidad de vida. La desnutrición se asocia, además, a una menor respuesta a la radioterapia y a la quimioterapia, o a una peor tolerancia a éstas. La desnutrición también altera los mecanismos de cicatrización y aumenta el riesgo de complicaciones quirúrgicas tales como la deshiscencia de suturas e infecciones. Tanto las complicaciones infecciosas como las derivadas de la cirugía comportan un aumento de la estancia hospitalaria, circunstancias que contribuyen a elevar los costes de los tratamientos. En último término, no deben olvidarse los efectos de la desnutrición sobre la mortalidad, asociándose la pérdida de peso severa a una menor supervivencia.The maximal expression of hyponutrition in cancer is tumoral cachexia, which will direct or indirectly account for mortality in one third of cancer patients

  16. 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.

  17. 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.

  18. Chronic Renal Failure, Cachexia, and Ghrelin

    Directory of Open Access Journals (Sweden)

    A. Laviano

    2010-01-01

    Full Text Available Protein energy wasting is frequently observed in patients with advanced chronic renal failure and end-stage renal disease. Anorexia and reduced food intake are critical contributing factors and negatively impact on patients' survival. Ghrelin is a prophagic peptide produced by the stomach and acting at the hypothalamic level to increase the activity of orexigenic neurons. In patients with chronic renal disease, plasma levels are increased as a likely effect of reduced renal clearance. Nevertheless, patients' food intake is significantly reduced, suggesting inflammation-mediated resistance of hypothalamic nuclei to peripheral signals. A number of forms of evidence show that ghrelin resistance could be overcome by the administration of exogenous ghrelin. Therefore, ghrelin has been proposed as a potential strategy to improve food intake in chronic renal failure patients with protein energy wasting. Preliminary data are encouraging although larger prospective clinical trials are needed to confirm the results and to identify those patients who are likely to benefit most from the administration of exogenous ghrelin.

  19. Effect of Xiaoyan Decoction on Cachexia and Tumor Growth in Mice with Lung Cancer%消岩汤对肺癌恶病质小鼠肿瘤生长的影响

    Institute of Scientific and Technical Information of China (English)

    张蕴超; 贾英杰; 杨佩颖; 黄敏娜

    2013-01-01

    Objective To observe the effect of Xiaoyan Decoction (antitumor decoction) on cachexia in mice with lung cancer and its antitumor mechanism. Methods Forty mice were randomized into the healthy group, lung cancer group, Xiaoyan Decoction group and megestrol acetate group, with 10 in each. The leptin content and the expressions of p53 and C-myc protein were observed after 12 days of continuous treatment. Results Comparing with the lung cancer group, the reaction, body hair and food intake improved significantly in the Xiaoyan Decoction group and megestrol acetate group (P<0. 01), especially the food intake in the Xiaoyan Decoction group (P<0. 01). The situation of reaction and body hair was the worst in the lung cancer group. The mice were sacrificed after treatment. Comparing with the healthy group, the bodyweights in the lung cancer group, Xiaoyan Decoction group and megestrol acetate group were significantly decreased (P<0. 05 or P<0. 01), especially in the lung cancer group (P<0. 01) , especially in the Xiaoyan Decoction group (P<0. 01). Comparing with the lung cancer group, the tumor weight was significantly decreased in the Xiaoyan Decoction group and megestrol acetate group on the 12th day of treatment (P<0. 01), especially in the Xiaoyan Decoction group (P<0. 01). Comparing with the healthy group, the leptin levels in the lung cancer group, Xiaoyan Decoction group and megestrol acetate group were decreased, especially in the lung cancer group and megestrol acetate group (P<0. 05). Comparing with the lung cancer group, the expressions of p53 were significantly increased in the Xiaoyan Decoction group and megestrol acetate group (P<0. 01) , especially in the Xiaoyan Decoction group (P<0. 01). Comparing with the lung cancer group, the expressions of C-myc were significantly decreased in the Xiaoyan Decoction group and megestrol acetate group (P<0. 01) , especially in the Xiaoyan Decoction group (P<0. 01). Conclusion Xiaoyan Decoction can improve appetite, body

  20. Early treatment with mirtazapine improves food intake and nutritional status in a gemcitabine-induced mild cachexia mouse model with pancreatic cancer%米氮平早期干预对轻度胰腺癌恶液质模型进食和营养状况的影响

    Institute of Scientific and Technical Information of China (English)

    吴建华; 贾林; 江舒曼

    2012-01-01

    AIM: To investigate the effect of early treatment with mirtazapine on food intake and nutritional status in a gemcitabine-induced mild cachexia mouse model with pancreatic cancer.METHODS: After a subcutaneous xenograft model of pancreatic cancer was established, 21 xenograft nude mice were randomly and equally divided into control group, early mirtazapine treatment group and late mirtazapine treatment group. The two treatment groups were given 10 mg/(kgd) mirtazapine once daily by oral gavage from day 1 and day 10 after transplantation, respectively. All animals were given 50 mg/kg of gemcitabine i.p. on days 10,13 and 16 after transplantation. All mice were sacrificed on day 28. Body weight, food intake, tumor size, subcutaneous fat, arm circumference and the time-effect relationship were compared among the three groups.RESULTS: There were no significant differences in tumor size, subcutaneous fat and arm circumference among the three groups (all P > 0.05). At week 4, food intake was significantly higher in the early mirtazapine treatment group than in the other two groups (both P 0.05).CONCLUSION: Early treatment with mirtazapine significantly improves food intake in the Gemcitabine-induced mild cachexia mouse model with pancreatic cancer, it can also postpone the processes of cachexia to some extent.%目的:探讨抗抑郁药米氮平早期干预对轻度胰腺癌恶液质模型进食量和营养状况的影响.方法:21只胰腺癌裸鼠皮下移植瘤模型随机分为对照组(A组)、米氮平早期干预组(B组)、米氮平后期治疗组(C组),每组7只.B、C组分别在术后第1天和第10天开始以米氮平10 mg/(kg.d),灌胃,术后第10、13、16天,3组动物分别腹腔注射吉西他滨(50 mg/kg).术后第28天处死裸鼠,比较3组动物体质量、进食量、肿瘤体积、皮下脂肪和臂围的变化.结果:3组胰腺癌移植瘤体积、皮下脂肪和臂围无明显差异(P>0.05).第4周B组进食量显著高于A组和C组(P<0.05)

  1. 中药消岩汤对肺癌恶病质大鼠摄食的瘦素抵抗机制研究%Mechanism Study on Leptin Resistance in Lung Cancer Cachexia Rats Treated by Xiaoyan Decoction

    Institute of Scientific and Technical Information of China (English)

    张蕴超; 贾英杰; 杨佩颖; 张欣; 李小江; 张莹; 朱津丽; 孙一予; 陈军

    2014-01-01

    resistance mechanism of Xiaoyan Decoction (XD) in lung cancer cachexia (LCC) rats.Methods An LCC rat model was established.Totally 40 rats were randomly divided into the normal control group,the LCC model group,the XD group,and the positive control group,10 in each group.After LCC model was set up,rats in the LCC model group were administered with normal saline,2 mL each time.Rats in the XD group were administered with XD at the daily dose of 2 mL.Those in the positive control group were administered with Medroxyprogesterone Acetate suspension (20 mg/kg) by gastrogavage at the daily dose of 2 mL.All medication lasted for 14 days.The general condition and tumor growth were observed.Serum levels of leptin and leptin receptor in the hypothalamus were detected using enzyme-linked immunosorbent assay.Contents of neuropeptide Y (NPY) and anorexia for genomic POMC were detected using real-time PCR technique.Results Serum leptin levels were lower in the LCC model group than in the normal control group with statistical significance (P < 0.05).Compared with the LCC model groups,serum leptin levels significantly increased in the XD group (P <0.01).Leptin receptor levels in the hypothalamus increased significantly in the LCC model group (P <0.01).Increased receptor levels in the LCG model group indicated that either XD or Medroxyprogesterone Acetate could effectively reduce levels of leptin receptor with statistical significance (P < 0.01).There was also statistical difference between the XD group and the positive control group (P < 0.05).Contents of NPY was higher in the LCC model group than in the other groups with statistical difference (P <0.05).There was no statistical difference in NPY between the normal control group and the rest 2 treatment groups (P >0.05).There was statistical difference in POMC between the normal control group and the LCC model group (P <0.05).POMC could be decreased in the XD group and the positive control group with statistical significance

  2. MG132对肿瘤恶病质小鼠骨骼肌消耗及TRAF6表达的影响%Effect of protease inhibitor MG132 on skeletal muscle consumption and expression of TRAF6 in cancer cachexia in mice

    Institute of Scientific and Technical Information of China (English)

    张刘平; 唐华; 郑曰勇; 周小雨; 朱萌; 寇耀

    2013-01-01

    Objective To investigate the effect of protease inhibitor MG132 on skeletal muscle consumption and the expression of TRAF6, Beclin-1 , MuRF1 and MAFbx in cancer cachexia. Methods Murine colon C26 adenocarci-noma cells were inoculated into male BALB/c mice to induce cancer cachexia. 24 male BALB/c mice were divided into 3 groups; healthy control group(HC) ;cancer cachexia group (CC)and MG132 treatment group (MG). Body weight and spontaneous activity were examined. Equal amount of physiological saline and 0.1mg/kg doses of MG132 were given intraperitoneally daily to CC and MG groups, respectively, on day 12 after tumor inoculation. All mice were sacrificed on day 19. Tumor and the left gastrocnemius muscle were accurately weighed, crosscut area of gastrocnemius muscle were measured. MRNA and protein level of TRAF6, Beclin1, MuRF1and MAFbx were detected by RT-PCR and Western blot, respectively. Results On-tumor body weight, spontaneous activity gastrocnemius muscle weight and crosscut area of CC group lower than HC group (P < 0. 05) , these indexes bounced significantly of MG group (P <0.05), but still lower than that in HC group (P <0.05). The mRNA and protein expression of TRAF6, Beclinl, MuRF1and MAFbx in the gastrocnemius muscle of CC group were significantly higher HC group (P<0.05), these indexes of MG group were significantly lower than those in CC group (P <0.05). Conclusions The improvement of skeletal muscle consumption in cancer cachexia by MG132 may be explaimed by its inhibition to TAF6 expression, thus suppressing autophagy-lysosome pathway and ubiquitin-proteasome pathway.%目的 探讨蛋白酶体抑制剂MG132对肿瘤恶病质骨骼肌消耗和TRAF6及其所调节的自噬溶酶体途径和泛素蛋白酶体途径相关因子Beclin-1、MuRF1和MAFbx基因表达的影响.方法 小鼠结肠腺癌C26细胞接种BALB/c小鼠诱导肿瘤恶病质模型.分为对照组(HC)、恶病质组(CC)和MG132治疗组(MG).监测体质量和

  3. 细菌移位与癌性恶液质的关系及对恶液质患者结局的影响%Association of bacterial translocation with cachexia and its influence on the outcome of gastric cancer patients

    Institute of Scientific and Technical Information of China (English)

    米磊; 郑红梅; 张坚; 焦学龙; 张佃良

    2012-01-01

    目的 探讨局限型进展期胃癌患者肠道细菌移位与恶液质的关系及其对患者结局的影响.方法 选取2008年1月至2009年7月预行手术治疗的胃癌恶液质患者60例,年龄及性别匹配的胃癌非恶液质患者50例,健康对照者55例.采用聚合酶链反应检测外周血细菌DNA片段,酶联免疫吸附实验检测外周血细胞因子浓度,流式细胞法检测外周血免疫学指标.所有入选对象随访两年,计算两年生存率.结果 恶液质组细菌移位发生率( 15/60,25.0%)显著高于非恶液质组(4/50,8.0%,P=0.019)和健康对照组(0/55,0.0%,P=0.000).细菌移位阳性的恶液质患者白细胞介素-1α (IL-1α)、IL-6、肿瘤坏死因子-α和干扰素-γ水平均显著高于细菌移位阴性的恶液质患者(P=0.012、P=0.003、P=0.036、P=0.017)和细菌移位阳性的非恶液质患者(P=0.011、P=0.034、P=0.000、P=0.022),并且其两年生存率明显低于细菌移位阴性的恶液质患者(P=0.023).胃癌患者CD3+T、CD4+T和自然杀伤细胞水平及CD4+ T/CD8+T显著低于健康对照组(P=0.023、P=0.031、P=0.016、P=0.041),CD8+T细胞水平显著高于健康对照组(P=0.038).结论 肠道细菌移位可能与局限型进展期胃癌患者恶液质的发生有关,并影响恶液质患者的长期生存.%Objective To investigate the association of bacterial translocation (BT) with cachexia and its impact on the outcome of gastric cancer patients.Methods Sixty cachectic gastric cancer patients,50 age- and sex-matched non-cachectic gastric cancer patients,and 55 healthy controls were enrolled in this study between January 2008 and July 2009.Polymerase chain reaction was performed to detect bacterial DNA in the peripheral blood of cancer patients and healthy controls,Cytokine levels were tested by enzyme-linked immunosorbent assay.Flow cytometry was used to detect immune indicators.All the enrolled patients were followed up for two years,and the two-year survival rate was

  4. 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

  5. Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia

    Directory of Open Access Journals (Sweden)

    Alessio Molfino

    2015-01-01

    Full Text Available Inflammation characterizes the course of acute and chronic diseases and is largely responsible for the metabolic and behavioral changes occurring during the clinical journey of patients. Robust data indicate that, during cancer, functional modifications within brain areas regulating energy homeostasis contribute to the onset of anorexia, reduced food intake, and increased catabolism of muscle mass and adipose tissue. In particular, functional changes are associated with increased hypothalamic concentration of proinflammatory cytokines, which suggests that neuroinflammation may represent the adaptive response of the brain to peripheral challenges, including tumor growth. Within this conceptual framework, the vagus nerve appears to be involved in conveying alert signals to the hypothalamus, whereas hypothalamic serotonin appears to contribute to triggering catabolic signals.

  6. N-3 fatty acids, cancer and cachexia: a systematic review of the literature.

    Science.gov (United States)

    Colomer, Ramón; Moreno-Nogueira, José M; García-Luna, Pedro P; García-Peris, Pilar; García-de-Lorenzo, Abelardo; Zarazaga, Antonio; Quecedo, Luis; del Llano, Juan; Usán, Luis; Casimiro, César

    2007-05-01

    Use of n-3 fatty acids (FA) has been reported to be beneficial for cancer patients. We performed a systematic review of the literature in order to issue recommendations on the clinical use of n-3 FA in the cancer setting. A systematic search was performed in MEDLINE, EMBASE, Cochrane and Healthstar databases. We selected clinical trials or prospective observational studies including patients with cancer and life expectancy >2 months, in which enteral supplements with n-3 FA were administered. Parameters evaluated individually were clinical (nutritional status, tolerance, survival and hospital stays), biochemical (inflammatory mediators), and functional (functional status, appetite and quality of life (QoL)). Seventeen studies met the inclusion criteria; eight were of high quality. The panel of experts established the following evidence: (1) oral supplements with n-3 FA benefit patients with advanced cancer and weight loss, and are indicated in tumours of the upper digestive tract and pancreas; (2) the advantages observed were: increased weight and appetite, improved QoL, and reduced post-surgical morbidity; (3) there is no defined pattern for combining different n-3 FA, and it is recommended to administer > 1.5 g/day; and (4) better tolerance is obtained administering low-fat formulas for a period of at least 8 weeks. All the evidences were grade B but for 'length of treatment' and 'advantage of survival' it was grade C. Our findings suggest that administration of n-3 FA (EPA and DHA) in doses of at least 1.5 g/day for a prolonged period of time to patients with advanced cancer is associated with an improvement in clinical, biological and QoL parameters.

  7. 癌症恶病质研究进展%Progress of cancer cachexia research

    Institute of Scientific and Technical Information of China (English)

    刘爱国; 李同度

    2003-01-01

    癌症恶病质是导致晚期癌症患者死亡的主要病症之一.但至今尚无满意可解释本病发病机制的理论,更无有效手段控制癌症恶病质的发展.本文从晚期癌症患者机体营养摄取不足、恶性肿瘤能量消耗增加、代谢紊乱、细胞因子的作用等角度出发来阐释本病的发病机制,并介绍了国际、国内针对本病的治疗方法.

  8. Effects of ghrelin on anorexia in tumor-bearing mice with eicosanoid-related cachexia.

    Science.gov (United States)

    Wang, Wenhua; Andersson, Marianne; Iresjö, Britt-Marie; Lönnroth, Christina; Lundholm, Kent

    2006-06-01

    Ghrelin is a novel brain-gut peptide that stimulates food intake and may secondarily increase body weight via a growth hormone secretagogue receptor (GHS-R). Tumor-bearing mice (MCG101), characterized by anorexia, fat loss and muscle wasting due to increased concentration of PGE2 and proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha), were provided ghrelin i.p. at a low (20 microg/day) and high dose (40 microg/day) to examine the ability of ghrelin to counteract tumor-induced anorexia. Immunohistochemical staining and Western blot analyses were used to identify GHS-R expression in the brain as well as its relationship to NPY expression in hypothalamic neurons. GHS-R mRNA in hypothalamus and ghrelin mRNA in gastric fundus were quantified by RT-PCR. Body composition was determined by carcass extractions. GHS-R expression in hypothalamus and plasma ghrelin levels were significantly increased in freely-fed tumor-bearing mice, while gastric fundus expression of ghrelin was unaltered compared to non-tumor-bearing mice (controls). Ghrelin treatment increased food intake, body weight and whole body fat at both low and high doses of ghrelin in normal controls, while tumor-bearing mice showed improved intake and body composition at the high dose of ghrelin only. Exogenous ghrelin normalized the GHS-R expression in hypothalamus from tumor-bearing mice without alterations in the gastric fundus expression of ghrelin. Tumor growth was not altered by exogenous ghrelin. Our results indicate that MCG 101-bearing mice became ghrelin resistant despite upregulation of hypothalamic GHS-R expression, which confirms similar indirect observations in cancer patients. Thus, other factors downstream of the ghrelin-GHS-R system appear to be more important than ghrelin to explain cancer-induced anorexia.

  9. 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.

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

    Science.gov (United States)

    2004-08-01

    Cell Physiol 166:506-511 Tilignac T, Temparis S, Combaret L, Taillandier D, Pouch MN, Cervek M, Cardenas DM, Le Bricon T, Debiton E, Samuels SE...and stimulate nancy (HHM)7. Breast and lung cancer cells that secrete osteoclastic bone resorption indirectly, rather than acting PTHrP in

  11. Effects of cytokines related cancer cachexia and EPA in cancer cachexia%癌性恶病质相关因子及EPA在癌性恶病质中的作用

    Institute of Scientific and Technical Information of China (English)

    沈静侠; 姜达

    2007-01-01

    癌症引起的恶病质即癌性恶病质(CC)是导致癌症患者死亡的主要原因,其致死率高达80%,但至今其发生机制尚不明确,更无有效手段逆转或控制其发展.二十碳五烯酸(EPA)能够促进瘦肌群的合成,因此有望成为治疗CC的主要药物.本文就CC相关的细胞因子、蛋白诱导分解因子、脂肪诱导因子等在CC发生中的作用作一综述,并探讨EPA逆转癌性恶病质的可行性.

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

    OpenAIRE

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

    2016-01-01

    Editors' Summary Background A heart attack, or acute myocardial infarction (AMI), is a potentially fatal medical emergency that occurs when part of the heart muscle dies because the blood supply to the heart becomes blocked, usually by a blood clot. Every year in the US alone, more than three-quarters of a million people have a heart attack—more than one person every minute. Heart attacks are usually caused by coronary artery disease. With age, fatty deposits (atherosclerotic plaque) coat the...

  13. Understanding and Management of Cancer Cachexia%肿瘤恶液质认识和处理

    Institute of Scientific and Technical Information of China (English)

    何义富; 季楚舒; 胡冰

    2011-01-01

    恶液质是恶性肿瘤患者的常见并发症,近80%晚期肿瘤患者会出现恶液质.恶液质往往与患者较低的生活质量和较差的预后相关,并引起肿瘤治疗的耐受性降低以及肿瘤治疗的敏感性下降.全文分析肿瘤恶液质综合征人群常见的体重下降和厌食的处理.

  14. Does Skeletal Muscle Mass Influence Breast Cancer? Evaluating Mammary Tumorigenesis and Progression in Genetically Hyper-Muscular Mice

    Science.gov (United States)

    2007-07-01

    preserve muscle in the end-stages of cancer, cancer cachexia . Up to 25% of breast cancer deaths may be attributed to muscle wasting from the complex... cachexia . 15. SUBJECT TERMS Breast cancer, skeletal muscle, myostatin, MPA, DMBA, Activin receptor, cachexia . 16. SECURITY CLASSIFICATION OF: 17...progress, we turned to another question relating skeletal muscle and cancer—pathological muscle wasting in cancer cachexia . (6) (7) (8) Cancer cachexia

  15. [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

    Introducción: La anorexia-caquexia es un síndrome frecuente en pacientes oncológicos, particularmente en etapas avanzadas: la prevalencia global de anorexia-caquexia para-neoplásica oscila entre el 20-40% en los enfermos en la fase diagnóstica, y entre el 70–80% en la fase avanzada de la enfermedad. En los enfermos oncológicos es frecuente la coexistencia de alteraciones digestivas estructurales o funcionales, secundarias al crecimiento tumoral y a los fenómenos sistémicos de carácter metabólico, determinados por la interrelación tumor-huésped específicos de la anorexia-caquexia. Objetivo: El objetivo de este trabajo es conocer la frecuencia de anorexia-caquexia, y su asociación con síntomas gastrointestinales en pacientes en terreno paliativo del Instituto Nacional de Cancerología, Ciudad de México, atendidos en el servicio de Cuidados Paliativos. Material y métodos: Se realizó un estudio transversal analítico. Se incluyeron 100 pacientes con diagnóstico de cáncer avanzado, con un rango de edad de 18 y 80 años, y una puntuación de Karnofsky > 50, así como un ECOG.

  16. Research Progress in Mechanism of Occurrence and Development with Cancer Cachexia%癌性恶病质发生发展机制研究进展

    Institute of Scientific and Technical Information of China (English)

    王琳

    2011-01-01

    癌性恶病质以短期内体重下降、脂肪及肌肉消耗为临床特征,此外还有厌食、低血糖、水肿、衰竭等.近年研究发现,引起恶病质的主要原因为代谢异常、宿主免疫系统产生致炎细胞因子、体循环中肿瘤产生的分解代谢因子等.全文就癌性恶病质发生发展机制的研究进展作一综述.

  17. 癌性恶病质代谢的研究现状%The Present Status of Research on Cancer Cachexia Metabolism

    Institute of Scientific and Technical Information of China (English)

    赫文; 徐玉清; 王文秀

    2004-01-01

    恶病质是癌症病人死亡的常见原因之一.与单纯性饥饿引起的营养不良不同,它的主要代谢改变是葡萄糖合成率的变化,糖异生、糖酵解增加,脂肪动员和氧化加速,蛋白质合成减少.

  18. Progress of Pathogenesis, Diagnosis and Treatment for Cancer Cachexia%肿瘤恶液质发病机制及诊治进展

    Institute of Scientific and Technical Information of China (English)

    李开春; 吴晴

    2007-01-01

    恶液质在肿瘤患者中普遍存在,且预示着较高的死亡率.恶液质发病机制是多方面的,细胞因子存恶液质过程巾扮演了非常重要的角色.恶液质的治疗涉及营养支持、针对致炎细胞因子治疗以及相天药物治疗等多个方面.

  19. 癌性恶病质的药物治疗进展%Progress on the Treatment of Cancer-related Anorexia and Cachexia Syndrome

    Institute of Scientific and Technical Information of China (English)

    王琳

    2014-01-01

    癌性恶病质是复杂的临床综合征,伴随体重下降、慢性炎症、新陈代谢紊乱、厌食、肌肉消耗、生活质量下降等.癌性恶病质治疗棘手,缺乏有效的治疗手段,目前许多新药的临床前及临床实验正在进行中.本文针对癌性恶病质药物治疗的现状及研究进展作一综述.

  20. Progress in Diagnosis and Drug Treatment in Cancer Cachexia%癌症恶病质的诊断及药物治疗进展

    Institute of Scientific and Technical Information of China (English)

    李斌; 杨全军; 郭澄

    2013-01-01

    癌症恶病质是恶性肿瘤的常见并发症,是由多因素引起的一系列虚弱症状为临床表现的综合征.全文就癌症恶病质的定义、诊断规范化及药物治疗研究进展进行综述.

  1. 浅谈从补肾健脾治疗肿瘤恶病质%Discussing the Treatment of Cancer Cachexia by Tonicing kidney and Strengthening Spleen

    Institute of Scientific and Technical Information of China (English)

    黄海福

    2010-01-01

    肿瘤恶病质是大多数中晚期肿瘤患者所面临的主要问题,本文从先古前贤论虚劳立足脾肾、脾肾两虚是其发生的重要机制、其重要致病因素"痰"、"瘀"与脾肾关系密切及其,临床表现与中医学脾肾亏虚证相一致4个方面阐述可从补肾健脾治疗肿瘤恶病质.

  2. Progress of Pathogenesis and Therapeutical Strategy for Cancer Cachexia%肿瘤恶病质发病机制及治疗策略研究进展

    Institute of Scientific and Technical Information of China (English)

    薛鹏; 吴晴

    2007-01-01

    恶病质是晚期肿瘤患者常见的临床综合征,现代医学对其病因和发病机制未彻底阐明.文章对近年来恶病质相关细胞因子、转录因子和泛素-蛋白酶体降解途径在其发病中的作用,以及有关治疗策略作一综述.

  3. [Dronabinol (delta9-tetrahydrocannabinol) in long-term treatment. Symptom control in patients with multiple sclerosis and spasticity, neuropathic pain, loss of appetite and cachexia].

    Science.gov (United States)

    Nauck, F; Klaschik, E

    2004-12-01

    Cannabinoid drugs have been used increasingly in the treatment of neuropathic pain and spasticity. Even though the evidence still is scarce, patients with multiple sclerosis seem to benefit substiantially from cannabinoid therapy. In a case report dose finding and long-term therapie with delta9-tetrahydrocannabinol are described. Dronabinol proved effective and was well tolerated in long-term treatment. Pain was reduced significantly and opioid requirements decreased. At the same time spasticity was reduced and appetite and weight increased. It still needs to bei discussed whether or not part of the positive effect on symptoms was probably mediated by psychomimetic effects. This case report shows, that dronabinol offers an additional therapeutic option in a palliative treatment concept for patiens with high symptom load.

  4. Ondervoeding bij patienten met kanker

    NARCIS (Netherlands)

    Dejong, C.H.C.; Olde Damink, S.

    2012-01-01

    The new practice guideline 'Malnutrition in patients with cancer' provides a good framework for the practical treatment of patients with impending cancer cachexia. Because the pathophysiology of cancer cachexia is multifactorial, its treatment requires a multimodal approach. Such multimodal treatmen

  5. The rationale forpreventing cancer cachexia:targeting excessive fatty acid oxidation

    Institute of Scientific and Technical Information of China (English)

    Chao-Nan Qian

    2016-01-01

    Cachexia commonly occurs at the terminal stage of cancer and has largely unclear molecular mechanisms. A recent study published inNature 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 dis‑cussed in this research highlight.

  6. 心脏恶病质综合征瓣膜置换术病人围术期护理%Perioperative Nursing Care of the Patients with Valvular Heart Disease Combined with Syndrome of Cardiac Cachexia

    Institute of Scientific and Technical Information of China (English)

    石琴; 张波; 张维青

    2004-01-01

    对21例心脏恶病质综合征行瓣膜置换术的病人行围术期护理,手术成功率90.48%.提出术前改善营养状况和心肺功能,术后加强心功能监护、呼吸道管理,及时处理心律失常、出血,纠正电解质紊乱及酸碱失衡,控制感染,是降低术后并发症获得良好预后的重要保证.

  7. 风湿性心脏病合并恶病质的围手术期营养支持%Perioperative nutritional support of rheumatic heart disease associated cardiac cachexia

    Institute of Scientific and Technical Information of China (English)

    罗春生; 张石江; 景华; 李德闽; 李忠东; 阮鹏

    2003-01-01

    目的:探讨风湿性心脏病(简称风心病)合并心源性恶病质病人围手术的营养支持与手术预后的关系. 方法:35例风心病合并心源性恶病质的病人分成两组(营养组和对照组),术前测定两组病人营养支持治疗前后体重指数(BMI)、血清营养指标参数、总淋巴细胞计数(TLC),观察手术后心包、纵隔引流液量、机械通气时间、并发症发生率和病死率. 结果:营养组和对照组在术前治疗前的各参数无统计学意义.经治疗后营养组与对照组比较BMI、血清营养指标参数、TLC明显增加(P<0.05),血清总胆红素明显下降(P<0.05),多巴胺用量及心包纵隔引流液量明显减少(P<0.05),机械通气时间、ICU时间、住院时间明显缩短(P<0.05),并发症明显减少(P<0.05).死亡2例均为对照组病人. 结论:术前的营养支持能明显改善风心病恶病质综合征(SOCC)瓣膜病病人的心功能及全身营养状况,缩短术后的机械通气时间及住院时间,减少心包、纵隔引流液量,促进切口的愈合,降低术后并发症,提高手术治疗成功率.

  8. Hypothalamic regulation of food intake during cancer

    NARCIS (Netherlands)

    Dwarkasing, J.T.

    2015-01-01

    Appetite is often reduced in patients with chronic illness, including cancer. Cancer anorexia, loss of appetite, frequently co-exists with cachexia, and the combined clinical picture is known as anorexia-cachexia syndrome. In patients suffering from this syndrome, anorexia considerably contributes t

  9. Eccentric contraction-induced myofiber growth in tumor-bearing mice.

    Science.gov (United States)

    Hardee, Justin P; Mangum, Joshua E; Gao, Song; Sato, Shuichi; Hetzler, Kimbell L; Puppa, Melissa J; Fix, Dennis K; Carson, James A

    2016-01-01

    Cancer cachexia is characterized by the progressive loss of skeletal muscle mass. While mouse skeletal muscle's response to an acute bout of stimulated low-frequency concentric muscle contractions is disrupted by cachexia, gaps remain in our understanding of cachexia's effects on eccentric contraction-induced muscle growth. The purpose of this study was to determine whether repeated bouts of stimulated high-frequency eccentric muscle contractions [high-frequency electrical muscle stimulation (HFES)] could stimulate myofiber growth during cancer cachexia progression, and whether this training disrupted muscle signaling associated with wasting. Male Apc(Min/+) mice initiating cachexia (N = 9) performed seven bouts of HFES-induced eccentric contractions of the left tibialis anterior muscle over 2 wk. The right tibialis anterior served as the control, and mice were killed 48 h after the last stimulation. Age-matched C57BL/6 mice (N = 9) served as wild-type controls. Apc(Min/+) mice lost body weight, muscle mass, and type IIA, IIX, and IIB myofiber cross-sectional area. HFES increased myofiber cross-sectional area of all fiber types, regardless of cachexia. Cachexia increased muscle noncontractile tissue, which was attenuated by HFES. Cachexia decreased the percentage of high succinate dehydrogenase activity myofibers, which was increased by HFES, regardless of cachexia. While cachexia activated AMP kinase, STAT3, and ERK1/2 signaling, HFES decreased AMP kinase phosphorylation, independent of the suppression of STAT3. These results demonstrate that cachectic skeletal muscle can initiate a growth response to repeated eccentric muscle contractions, despite the presence of a systemic cachectic environment.

  10. Clinical update on nursing home medicine: 2013.

    Science.gov (United States)

    Messinger-Rapport, Barbara J; Gammack, Julie K; Thomas, David R; Morley, John E

    2013-12-01

    This is the seventh article in the series of Clinical Updates on Nursing Home Care. The topics covered are antiresorptive drugs, hip fracture, hypertension, orthostatic hypotension, depression, undernutrition, anorexia, cachexia, sarcopenia, exercise, pain, and behavioral and psychological symptoms of dementia.

  11. Changes in IGF-I, urinary free cortisol and adipokines during dronabinol therapy in anorexia nervosa: Results from a randomised, controlled trial

    DEFF Research Database (Denmark)

    Andries, Alin; Frystyk, Jan; Flyvbjerg, Allan

    2015-01-01

    OBJECTIVE: Anorexia nervosa (AN) is characterised by complex neuroendocrine disturbances due to severe underweight, physical hyperactivity and purging behaviour. Cannabinoid agonists are used to palliate cachexia of various causes, but their interactions with the hormonal systems that are involved...

  12. Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD

    NARCIS (Netherlands)

    Remels, A.H.; Schrauwen, P.; Broekhuizen, R.; Willems, J.; Kersten, A.H.; Gosker, H.R.; Schols, A.M.

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is a multiorgan systemic disease. The systemic features are skeletal muscle weakness and cachexia, the latter being associated with systemic inflammation. The exact mechanisms underlying skeletal muscle dysfunction in COPD remain obscure. Recent evidence

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

    OpenAIRE

    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.

  14. 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.

  15. A Dog with Multiple Infections of Enteric Parasitic Zoonosis in Mashhad City, North-East of Iran; a Case Report

    OpenAIRE

    2016-01-01

    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 parasitolog...

  16. 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.

  17. 参附注射液对C26结肠癌荷瘤小鼠恶病质状态改善作用的实验研究%Experimental Study on Improvement Effect of Shenfu Injection on Status of Cachexia of Mice Bearing C26 Colon Cancer

    Institute of Scientific and Technical Information of China (English)

    潘磊; 翁家武; 陈培丰

    2012-01-01

    @@%目的:观察参附注射液对C26荷瘤小鼠恶病质状态的影响,并探讨其可能的作用机理.方法:建立BALB/C荷C26结肠癌小鼠恶病质模型,观察参附注射液对恶病质小鼠一般状态(如体重、摄食量、饮水量)的影响;检测小鼠血清TNF-α、TG、CHOL、ALB、BIB水平.结果:参附注射液能增加恶病质小鼠的摄食量及饮水量;抑制体重下降(P0.05).结论:参附注射液能改善荷瘤小鼠的恶病质状态,作用机理可能与调节TNF-α水平相关.

  18. Mechanisms of Cancer Cachexia-associated Muscle Atrophy:the Role of the Ubiquitin-proteasome Pathway%ATP-泛素-蛋白酶体途径在癌性恶液质肌萎缩中作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    袁磊; 吴国豪

    2008-01-01

    恶性肿瘤患者常伴随癌性恶液质(cancer cachexia,CC),CC表现为厌食、贫血、蛋白质分解增加、瘦组织群丢失、进行性体重下降甚至器官功能受损,但CC尚无统一诊断标准。研究发现,约半数癌症患者有CC,它是癌症患者死亡的重要原因。CC可导致患者生活质量下降,生存时间缩短,对治疗疗效降低。

  19. Perioperative enteral nutrition in rheumatic valve disease patients with cardiac cachexia: A report of 64 cases%风湿性瓣膜病心脏恶液质综合征患者围手术期应用胃肠内营养64例

    Institute of Scientific and Technical Information of China (English)

    赵铁夫; 王盛宇; 陈宝田; 张总刚; 刘筠; 郭永忠

    2007-01-01

    目的:观察胃肠内营养对心脏恶液质综合征患者手术后并发症发生率和远期生存率的影响.方法:①选择1999-08/2005-09首都医科大学附属北京安贞医院心脏外科收治的风湿性瓣膜病心脏恶液质综合征患者围手术期应用胃肠内营养64例,均对营养措施知情同意.②围手术期皆应用胃肠内营养,2.1~4.2 mJ/d;营养成分中,蛋白质∶脂肪∶糖=3∶6∶11,选用非整蛋白制剂作为胃肠内营养的主要原料,每晚应用含有大量活性双歧杆菌的酸奶封闭胃管.③采用电话与信函相结合方式对患者手术后生存率和心脏功能进行随访.共随访60个月.结果:64例3例失访,余随访60个月.1年生存率79%,3年生存率61%,5年生存率57%.术后心脏功能得到改善,心功能级别提高1~2级,体质量增加10%~30%.术后并发症13例(20%),死亡4例(6%).结论:围手术期应用胃肠内营养可以降低风湿性瓣膜病心脏恶液质综合征患者围手术期死亡率及并发症的发生率,提高远期生存率.

  20. Clinical studies of immunofunction and protein metabolism by combined supplementation of glutamine and recombinant human growth hormone in postoperative patients with cardiogenic cachexia of rheumatic heart disease%风湿性心脏病合并恶病质患者术后应用重组人生长激素的临床观察

    Institute of Scientific and Technical Information of China (English)

    王伟; 吴蔚; 何萍; 王海东; 杨康

    2009-01-01

    Objective To study the effects of recombinant human growth hormone(rhGH) on the treatment for valve replacement postoperative in rheumatic heart disease associated cardiac eaehex.Methods Fortytwo patients with rheumatic heart disease associated cardiac eachexia were divided into two groups.Group one(n=20,rhGH group) received standard enteral nutrition (15 kal·kg-1 · d-1)with rhGH 10U injection subeutaneously from postoperation day 7 to day 14 and group two(n = 22,eontrol group) received standard enteral nutrition (15 kal·kg-1· d-1) for the same period.Haemoglobin, serum total protein, serum albumin, blood glucose, handgrip exercise and triceps skin_fold thickness were determined.Meehanieal ventilation, hypostatie pneumonia incidence rate, and length of stay were observed.Results The levels of serum total protein, serum albumin and blood glucose eoneentration in the rhGH group at the 14th day were inereased significantly compared to that in the control group(P <0.01).Haemoglobin, triceps skinfold thiekness and handgrip exercise in rhGH group were significantly different from those in the control group(P <0.05).Postoperative meehanieal ventilation time, intensive care unit time, hospital stay time were signifieantly shorter than those in the eontrol group (P < 0.05), and hypostatie pneumonia was significantly lower than that in the eontroi group(P < 0.01).Conclusions The rhGH can obviously improve anabolie effects of patients with rheumatic heart disease associated cardiac eachexia whieh can reduce hypostatie pneumonia and shorten postoperative hospital stay time.%目的 探讨风湿性心脏病合并心源性恶病质综合征(SOCC)患者,瓣膜置换术后应用重组人生长激素的效果.方法 42例风湿性心脏病合并SOCC分成重组人生长激素rhGH组(治疗组)和对照组.治疗组(n=20)采用常规营养的肠内营养(总热卡15 kal·kg-1·d-1)+rhGH,其中rhGH每天皮下注射IOU,从术后第7-14 d共计7 d.对照组(n:22)仪采用常规营养的肠内营养(总热量15 kal·kg-1·d-1).术后第7 d和第14 d,分别测定血红蛋白、血浆总蛋白、白蛋白、血糖浓度和双手握力试验,观察机械通气时间、坠积性肺炎发生率,住院时间和营养学测量.结果 治疗组第14 d的血浆总蛋白、白蛋白、血糖浓度比对照组明显升高(P<0.01),血红蛋白、双手握力试验和三头肌皮褶厚度较治疗前明显提高(P<0.05);治疗组呼吸机辅助时间、1CU时间、术后时间(P<0.05)和坠积性肺炎的发生率(P<0.01)较对照组明显降低.结论 相对于单纯的常规营养,rhGH可以明显改善风心病恶病质综合征、瓣膜病换瓣术后患者的蛋白质合成代谢,减少坠积性肺炎的发生,减少住院时间.

  1. 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.

  2. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN) - a randomized multicentre trial

    OpenAIRE

    Kraft Matthias; Kraft Kathleen; Gärtner Simone; Mayerle Julia; Simon Peter; Weber Eckhard; Schütte Kerstin; Stieler Jens; Koula-Jenik Heide; Holzhauer Peter; Gröber Uwe; Engel Georg; Müller Cornelia; Feng You-Shan; Aghdassi Ali

    2012-01-01

    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)...

  3. 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.

  4. 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.

  5. 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...

  6. 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

  7. Differentiation of citrus Hop stunt viroid variants by real-time RT-PCR and high resolution melting analysis

    Science.gov (United States)

    Viroids are small, infectious, single-stranded RNA molecules that cause several important citrus diseases. Viroids are transmitted primarily in budwood, however, spread can also occur mechanically on pruning equipment, budding knives, hedging and topping equipment. Exocortis and cachexia are two we...

  8. Effect of infliximab on local and systemic inflammation in chronic obstructive pulmonary disease : A pilot study

    NARCIS (Netherlands)

    Dentener, Mieke A.; Creutzberg, Eva C.; Pennings, Herman-Jan; Rijkers, Ger T.; Mercken, Evi; Wouters, Emiel F. M.

    2008-01-01

    Background: Chronic obstructive pulmonary disease ( COPD) with cachexia is characterized by inflammation reflected by increased levels of tumor necrosis factor-alpha (TNF-alpha). Objectives: In this study, infliximab, an anti-TNF-alpha antibody, was evaluated for its effects on systemic ( plasma) an

  9. 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...

  10. Magestrol Acetate for Treatment of Anorexia Cahexia Patients between statins?

    OpenAIRE

    Haerani Rasyid, Haerani Rasyid

    2013-01-01

    - Cachexia Concensus Conference (2006) mendefinisikan kakheksia sebagai sindrom metabolik kompleks yang berhubungan dengan penyakit dasar yang ditandai adanya kehilangan otot dengan atau tanpa kehilangan massa lemak. Kakheksia merupakan kehilangan progresif otot skeiet dan jaringan adiposa yang disertai fatigue dan kelemahan yang umumnya ditemukan pada berbagai penyakit kronik sedangkan wasting yang terjadi pada pasien kakheksia disebabkan oleh berbagai faktor, diantaranya anoreksia dan ce...

  11. 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...

  12. Immunological perspectives on nutritional support during cancer

    NARCIS (Netherlands)

    Faber, J.

    2012-01-01

    Cachexia is a major problem in many cancer patients with a global incidence of malnutrition ranging from 30% to 90% during the course of cancer. The main characteristics of this chronic condition of catabolism include progressive weight loss, anorexia, wasting of muscle and adipose tissue, muscle we

  13. Weight loss induced by tyrosine kinase inhibitors of the vascular endothelial growth factor pathway.

    NARCIS (Netherlands)

    Desar, I.M.E.; Thijs, A.M.J.; Mulder, S.F.; Tack, C.J.J.; Herpen, C.M.L. van; Graaf, W.T.A. van der

    2012-01-01

    Weight loss, cachexia and sarcopenia are profound problems in the frail oncologic patients. With the development and increasing use of angiogenesis inhibitors in metastatic cancer patients, the question arises as to their influence on body weight and composition. Angiogenesis is not only important f

  14. Evaluation of body condition and weight loss in dogs presented to a veterinary oncology service.

    Science.gov (United States)

    Michel, Kathryn E; Sorenmo, Karin; Shofer, Frances S

    2004-01-01

    Cancer cachexia is a well-recognized syndrome in human patients that is characterized by progressive involuntary weight loss. The prevalence of this syndrome in veterinary cancer patients is unknown. This study's objective was to investigate the occurrence of weight loss and cachexia, as characterized by body condition scoring, in dogs presented to a veterinary oncology service. Information collected on 100 dogs included signalment, diagnosis, weight at time of diagnosis, and, when available, weight from a time approximately 12 months before diagnosis. Body condition was assessed by using a 9-point system based on body silhouette and palpation of adipose tissue (4-5 = optimal, 1 = extreme cachexia, 9 = extreme obesity). Muscle wasting was scored based on palpation of skeletal muscle (3 = no wasting, 2 = mild, 1 = moderate, 0 = severe). Only 4% of the dogs exhibited cachexia as defined by a body condition score or = 7). Fifteen percent had evidence of clinically relevant muscle wasting (dogs. At the time of diagnosis, 31% had maintained or gained weight, 31% had lost up to 5%, 14% had lost between 5 and 10%, and 23% had lost >10% of body weight. Overall, the percentage of dogs with signs indicating a decline in nutritional status was less than what has been reported for human cancer patients. Future studies should investigate the extent to which weight loss occurs in canine patients on an appropriate plane of nutrition as well as to establish whether an association exists between poor nutritional status and outcome in canine cancer patients.

  15. 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

  16. 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...

  17. Muscle atrophy in response to cytotoxic chemotherapy is dependent on intact glucocorticoid signaling in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Theodore P Braun

    Full Text Available Cancer cachexia is a syndrome of weight loss that results from the selective depletion of skeletal muscle mass and contributes significantly to cancer morbidity and mortality. The driver of skeletal muscle atrophy in cancer cachexia is systemic inflammation arising from both the cancer and cancer treatment. While the importance of tumor derived inflammation is well described, the mechanism by which cytotoxic chemotherapy contributes to cancer cachexia is relatively unexplored. We found that the administration of chemotherapy to mice produces a rapid inflammatory response. This drives activation of the hypothalamic-pituitary-adrenal axis, which increases the circulating level of corticosterone, the predominant endogenous glucocorticoid in rodents. Additionally, chemotherapy administration results in a significant loss of skeletal muscle mass 18 hours after administration with a concurrent induction of genes involved with the ubiquitin proteasome and autophagy lysosome systems. However, in mice lacking glucocorticoid receptor expression in skeletal muscle, chemotherapy-induced muscle atrophy is completely blocked. This demonstrates that cytotoxic chemotherapy elicits significant muscle atrophy driven by the production of endogenous glucocorticoids. Further, it argues that pharmacotherapy targeting the glucocorticoid receptor, given in concert with chemotherapy, is a viable therapeutic strategy in the treatment of cancer cachexia.

  18. Cross-talk between the heart and adipose tissue in cachectic heart failure patients with respect to alterations in body composition: a prospective study

    DEFF Research Database (Denmark)

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

    2014-01-01

    Cardiac cachexia (CC) is associated with changes in body composition. Lipolysis and increased energy expenditure caused by A- and B natriuretic peptides (NPs) have been suggested to play a role in CC. We tested the hypothesis that neurohormones and adipokines are associated with body composition...

  19. 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...

  20. Cockayne syndrome group B protein prevents the accumulation of damaged mitochondria by promoting mitochondrial autophagy

    DEFF Research Database (Denmark)

    Scheibye-Knudsen, Morten; Ramamoorthy, Mahesh; Sykora, Peter

    2012-01-01

    Cockayne syndrome (CS) is a devastating autosomal recessive disease characterized by neurodegeneration, cachexia, and accelerated aging. 80% of the cases are caused by mutations in the CS complementation group B (CSB) gene known to be involved in DNA repair and transcription. Recent evidence indi...

  1. Cachectic skeletal muscle response to a novel bout of low-frequency stimulation

    Science.gov (United States)

    Puppa, Melissa J.; Murphy, E. Angela; Fayad, Raja; Hand, Gregory A.

    2014-01-01

    While exercise benefits have been well documented in patients with chronic diseases, the mechanistic understanding of cachectic muscle's response to contraction is essentially unknown. We previously demonstrated that treadmill exercise training attenuates the initiation of cancer cachexia and the development of metabolic syndrome symptoms (Puppa MJ, White JP, Velazquez KT, Baltgalvis KA, Sato S, Baynes JW, Carson JA. J Cachexia Sarcopenia Muscle 3: 117–137, 2012). However, cachectic muscle's metabolic signaling response to a novel, acute bout of low-frequency contraction has not been determined. The purpose of this study was to determine whether severe cancer cachexia disrupts the acute contraction-induced response to low-frequency muscle contraction [low-frequency stimulation (LoFS)]. Metabolic gene expression and signaling was examined 3 h after a novel 30-min bout of contraction (10 Hz) in cachectic ApcMin/+ (Min) and C57BL/6 (BL-6) mice. Pyrrolidine dithiocarbamate, a STAT/NF-κB inhibitor and free radical scavenger, was administered systemically to a subset of mice to determine whether this altered the muscle contraction response. Although glucose transporter-4 mRNA was decreased by cachexia, LoFS increased muscle glucose transporter-4 mRNA in both BL-6 and Min mice. LoFS also induced muscle peroxisome proliferator-activated receptor-γ and peroxisome proliferator-activated receptor-α coactivator-1 mRNA. However, in Min mice, LoFS was not able to induce muscle proliferator-activated receptor-α coactivator-1 targets nuclear respiratory factor-1 and mitochondrial transcription factor A mRNA. LoFS induced phosphorylated-S6 in BL-6 mice, but this induction was blocked by cachexia. Administration of pyrrolidine dithiocarbamate for 24 h rescued LoFS-induced phosphorylated-S6 in cachectic muscle. LoFS increased muscle phosphorylated-AMP-activated protein kinase and p38 in BL-6 and Min mice. These data demonstrate that cachexia alters the muscle metabolic response

  2. A randomised feasibility study of EPA and Cox-2 inhibitor (Celebrex versus EPA, Cox-2 inhibitor (Celebrex, Resistance Training followed by ingestion of essential amino acids high in leucine in NSCLC cachectic patients - ACCeRT Study

    Directory of Open Access Journals (Sweden)

    Rogers Elaine S

    2011-11-01

    Full Text Available Abstract Background Cancer cachexia is a syndrome of progressive weight loss. Non-small cell lung cancer patients experience a high incidence of cachexia of 61%. Research into methods to combat cancer cachexia in various tumour sites has recently progressed to the combination of agents. The combination of the anti-cachectic agent Eicosapentaenoic acid (EPA and the cyclo-oxygenase-2 (COX-2 inhibitor celecoxib has been tested in a small study with some benefit. The use of progressive resistance training (PRT followed by the oral ingestion of essential amino acids (EAA, have shown to be anabolic on skeletal muscle and acceptable in older adults and other cancer groups. The aim of this feasibility study is to evaluate whether a multi-targeted approach encompassing a resistance training and nutritional supplementation element is acceptable for lung cancer patients experiencing cancer cachexia. Methods/Design Auckland's Cancer Cachexia evaluating Resistance Training (ACCeRT is an open label, prospective, randomised controlled feasibility study with two parallel arms. All patients will be treated with EPA and the COX-2 inhibitor celecoxib on an outpatient basis at the study site. In the experimental group patients will participate in PRT twice a week, followed by the ingestion of essential amino acids high in leucine. A total of 21 patients are planned to be enrolled. Patients will be randomised using 1:2 ratio with 7 patients enrolled into the control arm, and 14 patients into the treatment arm. The primary endpoint is the acceptability of the above multi-targeted approach, determined by an acceptability questionnaire. Discussion To our knowledge ACCeRT offers for the first time the opportunity to investigate the effect of stimulating the anabolic skeletal muscle pathway with the use of PRT along with EAA alongside the combination of EPA and celecoxib in this population. Trial registration Netherlands Trial Register (NTR: ACTRN12611000870954

  3. 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...

  4. Polioencephalomalacia and Heart Failure Secondary to Presumptive Thiamine Deficiency, Hepatic Lipidosis, and Starvation in 2 Abandoned Siamese Cats.

    Science.gov (United States)

    Anholt, H; Himsworth, C; Britton, A

    2016-07-01

    Two 4-year-old spayed female Siamese cats were seized by the British Columbia Society for the Prevention of Cruelty to Animals after confinement to an abandoned housing unit without food for 9 weeks. One cat was found dead, and the second was euthanized within 24 hours due to neurologic deterioration despite therapy. Polioencephalomalacia of the caudal colliculus, hepatic lipidosis, cachexia, and congestive heart failure with cardiomyocyte atrophy were identified in both cats through postmortem examination and attributed to a prolonged period of starvation. Brain lesions were likely the result of thiamine deficiency (Chastek paralysis), which can be associated with both malnutrition and liver disease. This case highlights the importance of thiamine supplementation during realimentation of cats with hepatic lipidosis. Heart failure resulting from cachexia may have contributed to the death of the first cat and the morbidity of the second cat.

  5. 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.

  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. 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.

  8. Anorexia: a taste of things to come?

    Science.gov (United States)

    Wilcock, Andrew

    2006-01-01

    Anorexia, the loss of the desire to eat, is common in patients with cancer. Studies report a prevalence of up to 66% and clinical practice suggests that it is an almost universal experience as the cancer progresses. It generally leads to a reduction in food intake that contributes to the development of malnutrition and cachexia, impairing quality of life and increasing morbidity and mortality. Successful curative or palliative treatment of the underlying cancer is an effective approach. When this is not possible, there are limited treatment options, which generally have not been shown to be practicable, tolerable, effective or safe in the long-term management of the cachexia-anorexia syndrome. Recent increases in the understanding of the physiology of energy intake and of the pathophysiology of anorexia are helping to guide the development of rational approaches. This journal club provides an outline of the pathophysiology of anorexia and highlights a paper that may provide an exciting glimpse of the future.

  9. Multi-omics Analysis of Serum Samples Demonstrates Reprogramming of Organ Functions Via Systemic Calcium Mobilization and Platelet Activation in Metastatic Melanoma.

    Science.gov (United States)

    Muqaku, Besnik; Eisinger, Martin; Meier, Samuel M; Tahir, Ammar; Pukrop, Tobias; Haferkamp, Sebastian; Slany, Astrid; Reichle, Albrecht; Gerner, Christopher

    2017-01-01

    Pathophysiologies of cancer-associated syndromes such as cachexia are poorly understood and no routine biomarkers have been established, yet. Using shotgun proteomics, known marker molecules including PMEL, CRP, SAA, and CSPG4 were found deregulated in patients with metastatic melanoma. Targeted analysis of 58 selected proteins with multiple reaction monitoring was applied for independent data verification. In three patients, two of which suffered from cachexia, a tissue damage signature was determined, consisting of nine proteins, PLTP, CD14, TIMP1, S10A8, S10A9, GP1BA, PTPRJ, CD44, and C4A, as well as increased levels of glycine and asparagine, and decreased levels of polyunsaturated phosphatidylcholine concentrations, as determined by targeted metabolomics. Remarkably, these molecules are known to be involved in key processes of cancer cachexia. Based on these results, we propose a model how metastatic melanoma may lead to reprogramming of organ functions via formation of platelet activating factors from long-chain polyunsaturated phosphatidylcholines under oxidative conditions and via systemic induction of intracellular calcium mobilization. Calcium mobilization in platelets was demonstrated to alter levels of several of these marker molecules. Additionally, platelets from melanoma patients proved to be in a rather exhausted state, and platelet-derived eicosanoids implicated in tumor growth were found massively increased in blood from three melanoma patients. Platelets were thus identified as important source of serum protein and lipid alterations in late stage melanoma patients. As a result, the proposed model describes the crosstalk between lipolysis of fat tissue and muscle wasting mediated by oxidative stress, resulting in the metabolic deregulations characteristic for cachexia.

  10. 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

    Polo, R.; C. Gómez-Candela; Miralles, C; Locutura, J.; J. Álvarez; Barreiro, F.; Bellido, D.; E. Câncer; D. Cánoves; P. Domingo; Estrada, V.; Fumaz, C. R.; 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 ...

  11. Marijuana Legalization: Impact on Physicians and Public Health

    OpenAIRE

    Wilkinson, Samuel T.; Yarnell, Stephanie; Radhakrishnan, Rajiv; Ball, Samuel A.; D'Souza, Deepak Cyril

    2015-01-01

    Marijuana is becoming legal in an increasing number of states for both medical and recreational use. Considerable controversy exists regarding the public health impact of these changes. The evidence for the legitimate medical use of marijuana or cannabinoids is limited to a few indications, notably HIV/AIDS cachexia, nausea/vomiting related to chemotherapy, neuropathic pain, and spasticity in multiple sclerosis. Although cannabinoids show therapeutic promise in other areas, robust clinical ev...

  12. Research Priorities in Geriatric Palliative Care: Nonpain Symptoms

    OpenAIRE

    Combs, Sara; Kluger, Benzi M.; Kutner, Jean S.

    2013-01-01

    Research addressing the burden, assessment, and management of nonpain symptoms associated with advanced illness in older adults is limited. While nonpain symptoms such as fatigue, sleep, dyspnea, anxiety, depression, cognitive impairment, nausea, and anorexia-cachexia are commonly noted by patients and clinicians, research quantifying their effects on quality of life, function, and other outcomes are lacking and there is scant evidence regarding management. Most available studies have focused...

  13. Drug/Nutrients Interaction in Neoplastic Patients Requiring Nutritional Support. Practical Advice with Special Focusing on Pancreatic Cancer

    OpenAIRE

    Ilaria Uomo; Adele Savoia

    2008-01-01

    Malnutrition and cachexia are frequent complaints in neoplastic disease [1, 2]. Nutritional support and pain treatment still remain the main treatment option for the majority of patients with cancer, particularly for those affected by pancreatic cancer who very often present an advanced stage of the disease at moment of first diagnosis [3, 4, 5]. Therefore, in their clinical practice, physicians are faced with the need for parenteral or enteral nutrition and with the contemporary requirement ...

  14. 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.

  15. A clinical approach to the nutritional care process in protein-energy wasting hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Mar Ruperto

    2014-04-01

    Full Text Available Introduction: 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. Objective: This review examines from a clinical-nutritional practice point of view: a nutritional status as a mortality causative factor; b phenotypic characteristics of malnutri-tion/wasting/cachexia, and c current trends of NCP with special emphasis on nutritional support and novel nutrient and pharmacologic adjunctive therapies in HD patients. Method: 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. Results: From all the epidemiological data analyzed, NCP was the suggested method for identifying malnut rition/ 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. Conclusion: 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.

  16. Naringin Inhibits Tumor Growth And Reduces Interleukin-6 And Tumor Necrosis Factor α Levels In Rats With Walker 256 Carcinosarcoma

    OpenAIRE

    Camargo C.A.; Gomes-Marcondes M.C.C.; Wutzki N.C.; Aoyama H.

    2012-01-01

    The flavonoid naringin is a polyphenolic compound that naturally occurs in citrus. Patients with cancer generally present features of malnutrition and cachexia. Levels of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) are raised in patients with cancer. This study was designed to analyze the in vivo effect of naringin in the therapeutic treatment of rats bearing Walker 256 carcinosarcoma (W256). Rats were treated intraperitoneally with different doses o...

  17. Molecular mechanisms and treatment options for muscle wasting eiseases

    OpenAIRE

    Rüegg, Markus A; Glass, David J.

    2010-01-01

    Loss of muscle mass can be the consequence of pathological changes, as observed in muscular dystrophies; or it can be secondary to cachexia-inducing diseases that cause muscle atrophy, such as cancer, heart disease, or chronic obstructive pulmonary disease; or it can be a consequence of aging or simple disuse. Although muscular dystrophies are rare, muscle loss affects millions of people worldwide.Wediscuss the molecular mechanisms involved in muscular dystrophy and in muscle atrophy and pres...

  18. Concomitant parenteral nutrition and systemic cytotoxic therapy in a metastatic colorectal cancer patient

    Directory of Open Access Journals (Sweden)

    A. A. Popov

    2012-01-01

    Full Text Available Pathologic nutrients metabolism presents a severe problem in metastatic colorectal cancer patients, especially those with canceromatosis. A hypermetabolism-catabolism syndrome frequently develops in in patients with progressing canceromatosis. This leads to cachexia anorexia syndrome, which significantly impedes available treatment options. Artificial nutrition allows to improve available treatment in such patients. We present a successful case of concomitant parenteral nutrition and systemic cytotoxic therapy in metastatic colorectal cancer patient with peritoneal canceromatosis.

  19. Respiratory Challenges in Breast Cancer: Potential for Enhanced Diagnostics and Therapy

    Science.gov (United States)

    2010-07-01

    of cancer cachexia and abnormal glucose metabolism in humans with cancer J Am Coll Nutr 11 445-56 Teicher B A, Lazo J S and Sartorelli A C 1981...AD_________________ Award Number: W81XWH-08-1-0447 TITLE: Respiratory Challenges in Breast Cancer : Potential for Enhanced...07-2010 2. REPORT TYPE Annual 3. DATES COVERED (From - To) (1 JUL 2009-30 JUN 2010 4. TITLE AND SUBTITLE Respiratory Challenges in Breast Cancer

  20. In Reply

    OpenAIRE

    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. 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.

  2. Appendicitis and Meckel's diverticulum in a femoral hernia: simultaneous De Garengeot and Littre's hernia.

    Science.gov (United States)

    Phillips, A W; Aspinall, S R

    2012-12-01

    This report presents the case of a 73-year-old woman who was admitted with sepsis, cachexia and confusion secondary to a strangulated femoral hernia containing both the appendix (De Garengeot hernia) and a Meckel's diverticulum (Littre's hernia). She underwent successful operative management and was discharged from hospital on the 10th post-operative day. This is the first report in the literature of a combined De Garengeot and Littre's hernia within a femoral hernia sac.

  3. 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...

  4. Hormonal Regulators of Appetite

    OpenAIRE

    Austin Juliana; Marks Daniel

    2008-01-01

    Obesity is a significant cause of morbidity and mortality worldwide. There has been a significant worsening of the obesity epidemic mainly due to alterations in dietary intake and energy expenditure. Alternatively, cachexia, or pathologic weight loss, is a significant problem for individuals with chronic disease. Despite their obvious differences, both processes involve hormones that regulate appetite. These hormones act on specific centers in the brain that affect the sensations of hunger a...

  5. Parenteral nutrition support for patients with pancreatic cancer. Results of a phase II study

    OpenAIRE

    Riess Hanno; Doerken Bernd; Stieler Jens; Gövercin Mehmet; Arnold Dirk; Pelzer Uwe; Oettle Helmut

    2010-01-01

    Abstract Background Cachexia is a common problem in patients (pts) suffering from upper gastrointestinal cancer. In addition, most of these patients suffer from malabsorption and stenosis of the gastrointestinal tract due to their illness. Various methods of supplementary nutrition (enteral, parenteral) are practised. In patients with advanced pancreatic cancer (APC), phase angle, determined by bio-electrical impedance analysis (BIA), seems to be a survival predictor. The positive influence o...

  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 canc...... in the ROg roup. Neither intention-to-treat analysis nor per-protocol-analysis revealed any statistically significant differences between the groups with respect to clinical outcomes....

  7. Treatment of Cancer Pain by Targeting Cytokines

    OpenAIRE

    Vendrell, I.; Macedo, D.; I. Alho; Dionísio, M. R.; Costa, L.

    2015-01-01

    Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be relate...

  8. Adaptations of Arginine's Intestinal-Renal Axis in Cachectic Tumor-Bearing Rats.

    Science.gov (United States)

    Buijs, Nikki; Vermeulen, Mechteld A R; Weeda, Viola B; Bading, James R; Houdijk, Alexander P J; van Leeuwen, Paul A M

    2015-01-01

    Malignancies induce disposal of arginine, an important substrate for the immune system. To sustain immune function, the tumor-bearing host accelerates arginine's intestinal-renal axis by glutamine mobilization from skeletal muscle and this may promote cachexia. Glutamine supplementation stimulates argi-nine production in healthy subjects. Arginine's intestinal-renal axis and the effect of glutamine supplementation in cancer cach-exia have not been investigated. This study evaluated the long-term adaptations of the interorgan pathway for arginine production following the onset of cachexia and the metabolic effect of glutamine supplementation in the cachectic state. Fischer-344 rats were randomly divided into a tumor-bearing group (n = 12), control group (n = 7) and tumor-bearing group receiving a glutamine-enriched diet (n = 9). Amino acid fluxes and net fractional extractions across intestine, kidneys, and liver were studied. Compared to controls, the portal-drained viscera of tumor-bearing rats took up significantly more glutamine and released significantly less citrulline. Renal metabolism was unchanged in the cachectic tumor-bearing rats compared with controls. Glutamine supplementation had no effects on intestinal and renal adaptations. In conclusion, in the cachectic state, an increase in intestinal glutamine uptake is not accompanied by an increase in renal arginine production. The adaptations found in the cachectic, tumor-bearing rat do not depend on glutamine availability.

  9. Genetic evidence that SMAD2 is not required for gonadal tumor development in inhibin-deficient mice

    Directory of Open Access Journals (Sweden)

    Weinstein Michael B

    2010-06-01

    Full Text Available Abstract Background Inhibin is a tumor-suppressor and activin antagonist. Inhibin-deficient mice develop gonadal tumors and a cachexia wasting syndrome due to enhanced activin signaling. Because activins signal through SMAD2 and SMAD3 in vitro and loss of SMAD3 attenuates ovarian tumor development in inhibin-deficient females, we sought to determine the role of SMAD2 in the development of ovarian tumors originating from the granulosa cell lineage. Methods Using an inhibin α null mouse model and a conditional knockout strategy, double conditional knockout mice of Smad2 and inhibin alpha were generated in the current study. The survival rate and development of gonadal tumors and the accompanying cachexia wasting syndrome were monitored. Results Nearly identical to the controls, the Smad2 and inhibin alpha double knockout mice succumbed to weight loss, aggressive tumor progression, and death. Furthermore, elevated activin levels and activin-induced pathologies in the liver and stomach characteristic of inhibin deficiency were also observed in these mice. Our results indicate that SMAD2 ablation does not protect inhibin-deficient females from the development of ovarian tumors or the cachexia wasting syndrome. Conclusions SMAD2 is not required for mediating tumorigenic signals of activin in ovarian tumor development caused by loss of inhibin.

  10. Cancer cachexia:pathogenic mechanisms and therapeutic perspectives%癌性恶病质发生机制及防治对策

    Institute of Scientific and Technical Information of China (English)

    吴国豪

    2015-01-01

    癌症恶病质是恶性肿瘤病人常见的症候群,也是恶性肿瘤常见的致死因素,直接影响肿瘤治疗效果,增加并发症发生率,降低病人的生活质量,甚至影响预后。目前认为,癌性恶病质是由肿瘤因素、机体因素及肿瘤和机体的相互作用而导致的机体代谢紊乱引起的代谢综合征。癌性恶病质的治疗应该是多方面的综合治疗,包括药物治疗、营养支持治疗、分子靶向治疗等。%Cancer cachexia is a syndrome of progressive nutritional depletion which causes significant morbidity and mortality in cancer patients. The pathogenetic mechanisms underlying cancer cachexia is a complex interaction between the host and the tumor. The therapeutic standard of care for cachexia remains undefined to date. Among the recognized approaches, use of anti-inflammatory agents, nutritional therapy, and molecular theory.

  11. Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer.

    Directory of Open Access Journals (Sweden)

    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.

  12. Metabolic sequelae of cancers (excluding bone marrow transplantation).

    Science.gov (United States)

    Body, J J

    1999-07-01

    The pathogenesis of cancer anorexia/cachexia is still unclear, partly explaining why its treatment remains disappointing. Anorexia plays a central role but cancer cachexia is more complex than chronic starvation. One of the key differences is the preferential mobilization of fat and the sparing of skeletal muscle in simple starvation compared to an equal mobilization of fat and skeletal muscle in cancer patients. An increase in basal energy expenditure also appears to play a contributory role in many patients. Cytokines, essentially but not exclusively tumor necrosis factor-alpha, play an essential pathogenic role and the syndrome can be compared to a low grade chronic inflammatory state. Parenteral nutrition could facilitate the administration of complete doses of chemotherapy or radiotherapy but no significant survival benefit or decrease in treatment-induced toxicity have been demonstrated in prospective randomized trials. The gut should have the preference for nutritional support. Percutaneous endoscopic gastrostomy is used more and more often in patients with a functionally intact gastrointestinal tract, especially in patients with head and neck cancer. Progestational drugs can to some extent stimulate appetite, food intake, energy level, increase weight and decrease the severity of nausea and vomiting. However, pharmacological treatment of cancer cachexia remains disappointing and more trials with anticytokine drugs, anabolic agents or polyunsaturated fatty acids should be conducted.

  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 UNLABELLED: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Ghrelin is a very promising treatment option for cardiac cachexia, with the analogue BIM-28131 (RM-131 being the

  14. Influence of dexamethasone on appetite and body weight in lung cancer patients

    Directory of Open Access Journals (Sweden)

    Šarčev Tatjana

    2008-01-01

    Full Text Available Introduction Anorexia and cachexia are the most common symptoms in cancer patients. They increase morbidity and mortality among cancer patients as well as complications of surgery, radiotherapy and chemotherapy. The most common drugs for treatment of cancer cachexia are corticosteroids and megestrol acetate. Material and Methods The purpose of this study was to determine the influence of dexamethasone on appetite loss and weight loss in lung cancer patients treated with chemotherapy. Group A (30 patients was treated with cisplatin, etoposide and standard supportive therapy, while group B (30 patients received, in addition to this treatment, dexamethasone in the dose of 8 mg intravenously per day (1-3 day of chemotherapy. Results There was a statistically significant difference in appetite loss between two groups after the second chemotherapy cycle favoring group A. The analysis of weight loss showed a statistically significant difference between two groups after both chemotherapy cycles, once again in favor of group A. Concerning the improvement of appetite and weight gain, there was no statistically significant difference between two groups after both chemotherapy cycles. Discussion Many double-blind randomized controlled studies showed beneficial symptomatic effect of corticosteroids in cancer cachexia, especially on the improvement of appetite, food intake and performance status. In most of the studies the weight gain was not recorded. The most effective type of corticosteroids, dose and route of administration have not been established. Conclusion Dexamethasone significantly decreases appetite loss and weight loss in lung cancer patients treated with chemotherapy, while it has no influence on appetite improvement and weight gain.

  15. Hypocupremia in patients receiving total parenteral nutrition.

    Science.gov (United States)

    Bozzetti, F; Inglese, M G; Terno, G; Pupa, A; Sequeira, C; Migliavacca, S

    1983-01-01

    Although hypocupremia is a well-known consequence of long-term total parenteral nutrition (TPN), its incidence as well as the duration of TPN necessary to induce it are still unsettled. The purpose of this study is to review the changes in serum copper level in 25 patients receiving TPN for a period longer than 2 wk (mean duration 6 wk) at the Istituto Nazionale Tumori of Milan and to evaluate the possible relationship of cupremia with the basic disease. Main indications for TPN included enterocutaneous fistulas (11 patients), cancer cachexia (10 patients), radiation enteropathy (two patients), and severe postoperative stricture following esophagogastric resection (two patients). Mean value of serum copper at the beginning of the study was 143 micrograms/100 ml (normal value 65-165 micrograms/100 ml), and the regression analysis showed a mean fall of 5.64 micrograms/100 ml/wk. Hypocupremia occurred in four patients (three with intestinal fistulas and one with radiation obstructive enteritis) at 5th, 6th, 9th, and 6th wk of TPN, respectively. No patient with cancer cachexia developed hypocupremia. No patient with hypocupremia had clinical evidence of a copper deficiency syndrome. We conclude that 1) hypocupremia does not occur within the first month of TPN; 2) its incidence is about 16% in patients intravenously fed for period longer than 2 wk; 3) it is more frequent in patients with enterocutaneous fistulas, whereas it never occurs in patients with cancer cachexia, and 4) it is not necessarily associated to a clinicometabolic syndrome of copper deficiency. Finally, the "nutritional" meaning of serum copper should be questioned in cancer patients since it could represent a "tumor marker."

  16. Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1.

    Directory of Open Access Journals (Sweden)

    Meng-Chuan Chen

    Full Text Available Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM or gemcitabine (TGM, markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC. The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1 production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis.

  17. New drug therapies for COPD.

    Science.gov (United States)

    Ross, Clare L; Hansel, Trevor T

    2014-03-01

    Clinical trials with new drugs for chronic obstructive pulmonary disease (COPD) have been performed. Viruses exacerbate COPD and bacteria may play a part in severe COPD; therefore, antibiotic and antiviral approaches have a sound rationale. Antiinflammatory approaches have been studied. Advances in understanding the molecular basis of other processes have resulted in novel drugs to target reactive oxidant species, mucus, proteases, fibrosis, cachexia, and muscle wasting, and accelerated aging. Studies with monoclonal antibodies have been disappointing, highlighting the tendency for infections and malignancies during treatment. Promising future directions are lung regeneration with retinoids and stem cells.

  18. Mitochondrial neurogastrointestinal encephalomyopathy: novel pathogenic mutations in thymidine phosphorylase gene in two Italian brothers.

    Science.gov (United States)

    Libernini, Laura; Lupis, Chiara; Mastrangelo, Mario; Carrozzo, Rosalba; Santorelli, Filippo Maria; Inghilleri, Maurizio; Leuzzi, Vincenzo

    2012-08-01

    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE, MIM 603041) is an autosomal recessive multisystem disorder occurring due to mutations in a nuclear gene coding for the enzyme thymidine phosphorylase (TYMP). Clinical features of MNGIE include gastrointestinal dysmotility, cachexia, ptosis or ophthalmoparesis, peripheral neuropathy, diffuse leukoencephalopathy, and signs of mitochondrial dysfunction in tissues. We report the clinical and molecular findings in two brothers in whom novel TYMP gene mutations (c.215-13_215delinsGCGTGA; c.1159 + 2T > A) were associated with different clinical presentations and outcomes.

  19. 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

    either 20 ml of FO or 20 ml of rapeseed oil (RO) daily. Patients were evaluated every three weeks. Twenty-five patients participated in the study for more than 21 days. The RBC content in FO-group increased with 35%, 137% and 44%, respectively (p ...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...

  20. Food intake, tumor growth, and weight loss in EP2 receptor subtype knockout mice bearing PGE2-producing tumors

    OpenAIRE

    Iresjö, Britt‐Marie; Wang, Wenhua; Nilsberth, Camilla; Andersson, Marianne; LÖNNROTH, CHRISTINA; Smedh, Ulrika

    2015-01-01

    Previous studies in our laboratory have demonstrated that prostaglandin (PG) E2 is involved in anorexia/cachexia development in MCG 101 tumor‐bearing mice. In the present study, we investigate the role of PGE receptor subtype EP2 in the development of anorexia after MCG 101 implantation in wild‐type (EP2+/+) or EP2‐receptor knockout (EP2−/−) mice. Our results showed that host absence of EP2 receptors attenuated tumor growth and development of anorexia in tumor‐bearing EP2 knockout mice compar...

  1. Evidence-based practices for the prevention of weight loss in nursing home residents.

    Science.gov (United States)

    Dyck, Mary J; Schumacher, Julie Raeder

    2011-03-01

    Weight loss is common among nursing home residents. Food intake is often inadequate for elderly residents but is only one of several factors contributing to potential weight loss. Three common issues resulting in weight loss include starvation (or wasting), cachexia, and sarcopenia. Significant weight loss leads to increased mortality, increased morbidity, and decreased quality of life. The purpose of this article is to discuss the geriatric syndrome of weight loss in elderly nursing home residents and provide recommendations to decrease and prevent weight loss. A list of available evidence-based protocols related to weight loss issues is provided.

  2. Vitamin B12 deficit and development of geriatric syndromes

    Directory of Open Access Journals (Sweden)

    Ocampo Chaparro, José Mauricio

    2013-03-01

    Full Text Available Vitamin B12 deficiency or cyanocobalamin is a common condition in the elderly. It is repeatedly overlooked due to multiple clinical manifestations that can affect the blood, neurological, gastrointestinal, and cardiovascular systems, skin and mucous membranes. The various presentations of vitamin B12 deficiency are related to the development of geriatric syndromes like frailty, falls, cognitive impairment, and geriatric nutritional syndromes like protein-energy malnutrition and failure to thrive, in addition to enhancing aging anorexia and cachexia. Therefore, interventions must be developed to include their screening and diagnosis to make early and appropriate treatment to prevent its complications before they become irreversible.

  3. Déficit de vitamina B12 y desarrollo de síndromes geriátricos.

    Directory of Open Access Journals (Sweden)

    Jose Mauricio Ocampo

    2013-03-01

    Full Text Available Vitamin B12 deficiency or cyanocobalamin is a common condition in the elderly. It is repeatedly overlooked due to multiple clinical manifestations that can affect the blood, neurological, gastrointestinal, and cardiovascular systems, skin and mucous membranes. The various presentations of vitamin B12 deficiency are related to the development of geriatric syndromes like frailty, falls, cognitive impairment, and geriatric nutritional syndromes like protein-energy malnutrition and failure to thrive, in addition to enhancing aging anorexia and cachexia. Therefore, interventions must be developed to include their screening and diagnosis to make early and appropriate treatment to prevent its complications before they become irreversible.

  4. 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.

  5. Weight loss induced by tyrosine kinase inhibitors of the vascular endothelial growth factor pathway.

    Science.gov (United States)

    Desar, Ingrid M E; Thijs, Annemarie M J; Mulder, Sasja F; Tack, Cees J J; van Herpen, Carla M L; van der Graaf, Winette T A

    2012-02-01

    Weight loss, cachexia and sarcopenia are profound problems in the frail oncologic patients. With the development and increasing use of angiogenesis inhibitors in metastatic cancer patients, the question arises as to their influence on body weight and composition. Angiogenesis is not only important for the growth, development and metastatic potential of tumors but also for physiological processes in adipogenesis. A less known approach of angiogenesis inhibitors is their experimental use in obese models. This review focuses on the effects on the body weight and composition of angiogenesis inhibitors, especially of those targeting the vascular endothelial growth factor pathway.

  6. Cryptosporidium varanii infection in leopard geckos (Eublepharis macularius in Argentina

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. The relation of muscle protein degradation and 26S proteasome%肌肉蛋白降解与蛋白酶复合体

    Institute of Scientific and Technical Information of China (English)

    谭银玲

    2004-01-01

    The ubiquitin-dependent 20s/26s proteasome system is the capital pathway of exo-lyso-some proteolysis within eukaryotic cell. Under conditions of denervation, starvation, glucocorticoid, infection,tumor, bum and so on, the proteasome system was stimulated tofast. Glucocorticoid, insulin, thyroid honnone,TNFα and IL-1β degrade protein, which results in muscle lose cle protein degradation and the proteasome system. Inhibition or activation of the proteasome system was approved to be a novel means of treatment with cachexia and negative nitrogen balance.

  9. Vesical metastasis of gastric adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Alberto A. Antunes

    2004-10-01

    Full Text Available Metastatic vesical tumors are rare, and constitute approximately 1% of all neoplasias affecting this organ. The authors report the case of a 63-year old woman with vesical metastasis of gastric adenocarcinoma. Patient presented signs of cachexia and complained of left lumbar pain and dysuria unresponsive to antibiotic therapy for approximately 5 months. She reported a previous partial gastrectomy due to ulcerative undifferentiated gastric adenocarcinoma 1 year and 9 months before. Cystoscopy revealed an extensive vegetative lesion in bladder, occupying its entire mucosal surface. The biopsy revealed metastatic signet-ring cell adenocarcinoma.

  10. 细胞因子与恶病质相关因子的关系

    Institute of Scientific and Technical Information of China (English)

    张敏; 李贵新

    2011-01-01

    @@ 癌症恶病质(cancer cachexia,CC)是以体质量下降、肌肉萎缩及脂肪组织消耗等进行性营养消耗为特点的多器官综合征,CC是多种原因导致代谢紊乱,包括厌食、贫血、糖代谢异常、脂肪组织分解、蛋白异常代谢及胰岛素抵抗等[1].

  11. Nutritional support of patients with cancer of the gastrointestinal tract.

    Science.gov (United States)

    Daly, J M; Redmond, H P; Lieberman, M D; Jardines, L

    1991-06-01

    Malnutrition is extremely common in patients with malignant disease. Whereas the causes are multifactorial, the predominant factor is the imbalance between nutrient intake and host nutrient requirements. Furthermore, the evidence suggests that cachexia is related to abnormal changes in host intermediary metabolism induced by host-tumor interactions, and endogenous peptides such as TNF may be important mediators. The role of nutritional therapy in cancer patients remains to be defined. Clearly, patients with severe malnutrition benefit from nutritional intervention. However, the benefit of nutritional therapy in less severe cases of malnutrition as an adjuvant to oncologic therapy has yet to be established.

  12. [Veterinary medicine comment on camel medicine in Fan-mu tsuan yen-fang].

    Science.gov (United States)

    von den Driesch, A

    1997-01-01

    This short paragraph tries to identify the camel diseases compiled in the old chinese text according to modern veterinary terms. Due to the specific terminology of the camel treatise and its overall scarce symptomatology the diseases are difficult to evaluate. The majority of them obviously deal with acute infectious diseases which manifest themselves under such symptoms as high fever, depression, anorexia, cachexia, diarrhoea, general weakness, etc. But there are some diseases and ailments which can be interpreted in modern terms my means of the symptoms, descriptions and cures, e.g. mange, paradontosis and wry-neck syndrome.

  13. Pediatric patient with systemic lupus erythematosus & congenital acquired immunodeficiency syndrome: An unusual case and a review of the literature

    Directory of Open Access Journals (Sweden)

    Rezaee Fariba

    2008-05-01

    Full Text Available Abstract The coexistence of systemic lupus erythematosus (SLE in patients with congenital human immunodeficiency virus (HIV infection is rare. This is a case report of a child diagnosed with SLE at nine years of age. She initially did well on non-steroidal anti-inflammatory agents, hydroxychloroquine, and steroids. She then discontinued her anti-lupus medications and was lost to follow-up. At 13 years of age, her lupus symptoms had resolved and she presented with intermittent fevers, cachexia, myalgias, arthralgias, and respiratory symptoms. Through subsequent investigations, the patient was ultimately diagnosed with congenitally acquired immunodeficiency syndrome (AIDS.

  14. 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.

  15. [A potential of selective androgen receptor modulator(SARM)for the therapy of osteoporosis].

    Science.gov (United States)

    Yanase, Toshihiko

    2016-07-01

    In recent years, the drugs, which show anabolic, effect on bone and muscle without stimulating prostate has been developed. They show tissue-specific selective androgen actions and called selective androgen receptor modulators(SARMs). The development of drug targeting bone and muscle in male is very promising as a treatment tool for osteoporosis and sarcopenia in the near future. The clinical study is under going especially in the field of cachexia associated with cancer, but unfortunately there is no drug in the current market at present. The current situation of the development of SARMs will be reviewed.

  16. 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.

  17. Common symptoms in advanced cancer.

    Science.gov (United States)

    Lagman, Ruth L; Davis, Mellar P; LeGrand, Susan B; Walsh, Declan

    2005-04-01

    The key points of this article are anorexia and cachexia are: A major cause of cancer deaths. Several drugs are available to treat anorexia and cachexia. Dyspnea in cancer usually is caused by several factors. Treatment consists of reversing underlying causes, empiric bronchodilators, cortico-steroids--and in the terminally ill patients-opioids, benzodiazepines,and chlorpromazine. Delirium is associated with advanced cancer. Empiric treatment with neuroleptics while evaluating for reversible causes is a reasonable approach to management. Nausea and vomiting are caused by extra-abdominal factors (drugs,electrolyte abnormalities, central nervous system metastases) or intra-abdominal factors (gastroparesis, ileus, gastric outlet obstruction, bowel obstruction). The pattern of nausea and vomiting differs depending upon whether the cause is extra- or intra-abdominal. Reversible causes should be sought and empiric metoclopramide or haloperidol should be initiated. Fatigue may be caused by anemia, depression, endocrine abnormalities,or electrolyte disturbances that should be treated before using empiric methylphenidate. Constipation should be treated with laxatives and stool softeners. Both should start with the first opioid dose.

  18. Chronic heart failure and micronutrients.

    Science.gov (United States)

    Witte, K K; Clark, A L; Cleland, J G

    2001-06-01

    Heart failure (HF) is associated with weight loss, and cachexia is a well-recognized complication. Patients have an increased risk of osteoporosis and lose muscle bulk early in the course of the disease. Basal metabolic rate is increased in HF, but general malnutrition may play a part in the development of cachexia, particularly in an elderly population. There is evidence for a possible role for micronutrient deficiency in HF. Selective deficiency of selenium, calcium and thiamine can directly lead to the HF syndrome. Other nutrients, particularly vitamins C and E and beta-carotene, are antioxidants and may have a protective effect on the vasculature. Vitamins B6, B12 and folate all tend to reduce levels of homocysteine, which is associated with increased oxidative stress. Carnitine, co-enzyme Q10 and creatine supplementation have resulted in improved exercise capacity in patients with HF in some studies. In this article, we review the relation between micronutrients and HF. Chronic HF is characterized by high mortality and morbidity, and research effort has centered on pharmacological management, with the successful introduction of angiotensin-converting enzyme inhibitors and beta-adrenergic antagonists into routine practice. There is sufficient evidence to support a large-scale trial of dietary micronutrient supplementation in HF.

  19. Expression of TRAF6 and ubiquitin mRNA in skeletal muscle of gastric cancer patients

    Directory of Open Access Journals (Sweden)

    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.

  20. Oxidative stress, redox signaling pathways, and autophagy in cachectic muscles of male patients with advanced COPD and lung cancer.

    Science.gov (United States)

    Puig-Vilanova, Ester; Rodriguez, Diego A; Lloreta, Josep; Ausin, Pilar; Pascual-Guardia, Sergio; Broquetas, Joan; Roca, Josep; Gea, Joaquim; Barreiro, Esther

    2015-02-01

    Muscle dysfunction and wasting are predictors of mortality in advanced COPD and malignancies. Redox imbalance and enhanced protein catabolism are underlying mechanisms in COPD. We hypothesized that the expression profile of several biological markers share similarities in patients with cachexia associated with either COPD or lung cancer (LC). In vastus lateralis of cachectic patients with either LC (n=10) or advanced COPD (n=16) and healthy controls (n=10), markers of redox balance, inflammation, proteolysis, autophagy, signaling pathways, mitochondrial function, muscle structure, and sarcomere damage were measured using laboratory and light and electron microscopy techniques. Systemic redox balance and inflammation were also determined. All subjects were clinically evaluated. Compared to controls, in both cachectic groups of patients, a similar expression profile of different biological markers was observed in their muscles: increased levels of muscle protein oxidation and ubiquitination (pmuscle structural abnormalities and sarcomere disruptions were significantly greater (pmuscles of both cachectic patient groups than in controls (pmuscles of cachectic COPD patients (pmuscle wasting and sarcomere disruption in patients with respiratory cachexia: LC and COPD.

  1. CLA reduces inflammatory mediators from A427 human lung cancer cells and A427 conditioned medium promotes differentiation of C2C12 murine muscle cells.

    Science.gov (United States)

    Oraldi, Manuela; Maggiora, Marina; Paiuzzi, Elena; Canuto, Rosa A; Muzio, Giuliana

    2013-01-01

    Conjugated linoleic acid (CLA) is thought to have anti-proliferative and anti-inflammatory properties, but its effect on cancer cachexia is unknown. Two effects were here investigated: that of CLA on inflammatory mediator production in human lung cancer cells, and that of reduced mediators on the myogenic differentiation of murine muscle C2C12 cells. The latter cells were grown in medium conditioned by human lung cancer A427 cells, with or without CLA, to mimic only the effect of molecules released from the tumor "in vivo", excluding the effect of host-produced cachectic factors. The results obtained show that CLA was found to reduce the production of tumor necrosis factor-α, interleukin (IL)-1β and prostaglandin E2 (PGE2), but had no effect on IL-6 production. The mechanisms underlying the effect of CLA on cytokine or PGE2 release in A427 cells are probably mediated by activation of peroxisome proliferator-activated receptor (PPAR)α, which increased at 24 h CLA treatment. In turn, the reduced content of inflammatory mediators in medium conditioned by A427 cells, in the presence of CLA, allowed muscle cells to proliferate, again by inducing PPAR. The involvement of PPARα was demonstrated by treatment with the antagonist MK-886. The findings demonstrate the anti-inflammatory and myogenic action of CLA and point to its possible application as a novel dietary supplement and therapeutic agent in inflammatory disease states, such as cachexia.

  2. Omega-3 fatty acid effects on biochemical indices following cancer surgery.

    Science.gov (United States)

    Stehr, Sebastian N; Heller, Axel R

    2006-11-01

    Epidemiological studies have indicated that a high intake of saturated fat and/or animal fat increases the risk of colon and breast cancer. Laboratory and clinical investigations have shown a reduced risk of colon carcinogenesis after alimentation with omega-3 fatty acids, as found in fish oil. Mechanisms accounting for these anti-tumor effects are reduced levels of PGE(2) and inducible NO synthase as well as an increased lipid peroxidation, or translation inhibition with subsequent cell cycle arrest. Further, omega-3 eicosapentaenoic acid is capable of down-regulating the production and effect of a number of mediators of cachexia, such as IL-1, IL-6, TNF-alpha and proteolysis-inducing factor. In patients with advanced cancer, it is possible to increase energy and protein intake via an enteral or parenteral route, but this seems to have little impact on progressive weight loss. Fish oil administration improved patients' conditions in cancer cachexia and during radio- and chemotherapy. In patients undergoing tumor resection surgery we observed improvement of liver and pancreas biochemical indices when omega-3 fatty acids were administered. This paper is a review of recent developments in the field of nutrition in cancer patients with emphasis on the acute phase response following cancer surgery and the beneficial aspects of fish oil administration.

  3. 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.

  4. Grape polyphenols and propolis mixture inhibits inflammatory mediator release from human leukocytes and reduces clinical scores in experimental arthritis.

    Science.gov (United States)

    Mossalayi, M D; Rambert, J; Renouf, E; Micouleau, M; Mérillon, J M

    2014-02-15

    Polyphenols from red fruits and bee-derived propolis (PR) are bioactive natural products in various in vitro and in vivo models. The present study shows that hematotoxicity-free doses of grape polyphenols (GPE) and PR differentially decreased the secretion of pro-inflammatory cytokines from activated human peripheral blood leucocytes. While GPE inhibited the monocytes/macrophage response, propolis decreased both monokines and interferon γ (IFNγ) production. When used together, their distinct effects lead to the attenuation of all inflammatory mediators, as supported by a significant modulation of the transcriptomic profile of pro-inflammatory genes in human leukocytes. To enforce in vitro data, GPE+PR were tested for their ability to improve clinical scores and cachexia in chronic rat adjuvant-induced arthritis (AA). Extracts significantly reduced arthritis scores and cachexia, and this effect was more significant in animals receiving continuous low doses compared to those receiving five different high doses. Animals treated daily had significantly better clinical scores than corticoid-treated rats. Together, these findings indicate that the GPE+PR combination induces potent anti-inflammatory activity due to their complementary immune cell modulation.

  5. 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

  6. Poor Outcome in a Mitochondrial Neurogastrointestinal Encephalomyopathy Patient with a Novel TYMP Mutation: The Need for Early Diagnosis

    Directory of Open Access Journals (Sweden)

    Mauro Scarpelli

    2012-12-01

    Full Text Available Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE is a devastating autosomal recessive disorder due to mutations in TYMP, which cause loss of function of thymidine phosphorylase (TP, nucleoside accumulation in plasma and tissues and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped TP therapy and newer, promising therapies are expected in the near future. However, successful treatment is strictly related to early diagnosis. We report on an incomplete MNGIE phenotype in a young man harboring the novel heterozygote c.199 C>T (Q67X mutation in exon 2, and the previously reported c.866 A>C (E289A mutation in exon 7 in TYMP. The correct diagnosis was achieved many years after the onset of symptoms and unfortunately, the patient died soon after diagnosis because of multiorgan failure due to severe malnutrition and cachexia before any therapeutic option could be tried. To date, early diagnosis is essential to ensure that patients have the opportunity to be treated. MNGIE should be suspected in all patients who present with both gastrointestinal and nervous system involvement, even if the classical complete phenotype is lacking.

  7. MRI findings of serous atrophy of bone marrow and associated complications

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  8. 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.

  9. Mitochondria dysfunction in lung cancer-induced muscle wasting in C2C12 myotubes

    Directory of Open Access Journals (Sweden)

    Julie eMcLean

    2014-12-01

    Full Text Available Aims: Cancer cachexia is a syndrome which results in severe loss of muscle mass and marked fatigue. Conditioned media from cachexia-inducing cancer cells triggers metabolic dysfunction in skeletal muscle, including decreased mitochondrial respiration, which may contribute to fatigue. We hypothesized that Lewis lung carcinoma conditioned medium (LCM would impair the mitochondrial electron transport chain (ETC and increase production of reactive oxygen species, ultimately leading to decreased mitochondrial respiration. We incubated C2C12 myotubes with LCM for 30 minutes, 2hrs, 4hrs, 24hrs or 48hrs. We measured protein content by western blot; oxidant production by 2′,7′-dichlorofluorescin diacetate (DCF, 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF, and MitoSox; cytochrome c oxidase activity by oxidation of cytochrome c substrate; and oxygen consumption rate (OCR of intact myotubes by Seahorse XF Analyzer. Results: LCM treatment for 2hrs or 24hrs decreased basal OCR and ATP-related OCR, but did not alter the content of mitochondrial complexes I, III, IV and V. LCM treatment caused a transient rise in reactive oxygen species (ROS. In particular, mitochondrial superoxide (MitoSOX was elevated at 2hrs. 4-Hydroxynonenal, a marker of oxidative stress, was elevated in both cytosolic and mitochondrial fractions of cell lysates after LCM treatment. Conclusion: These data show that lung cancer-conditioned media alters electron flow in the ETC and increases mitochondrial ROS production, both of which may ultimately impair aerobic metabolism and decrease muscle endurance.

  10. 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.

  11. Chinese medicine for advanced cancer patients quality of life impact of treatment progress%中医药对中晚期肿瘤患者生存质量影响治疗进展

    Institute of Scientific and Technical Information of China (English)

    丰哲; 林宗汉; 黄有荣; 郝巍琳

    2011-01-01

    From medicine in cancer pain, chemotherapy, immune function decline and the cancer cachexia and the common symptoms of treatment of 4 in an overview of Chinese medicine for advanced neoplasms in patients on quality of life, that Chinese medicine can reduce the late cancer pain, improve immune function in patients after chemotherapy, to improve the cachexia associated with cancer and a variety of symptoms in advanced cancer patients on quality of life has a unique role.%从中医药在癌性疼痛、对化疗后免疫机能下降以及对肿瘤恶病质及常见症状的治疗4个方面综述了中医药对中晚期肿癌患者生存质量的影响,认为中医药能减轻中晚期肿瘤疼痛,提高化疗后患者免疫功能,改善恶病质及各种与癌症相关症状,在中晚期肿瘤患者生活质量研究中具有独特的作用.

  12. Protein-energy malnutrition in the rehabilitation setting: Evidence to improve identification.

    Science.gov (United States)

    Marshall, Skye

    2016-04-01

    Methods of identifying malnutrition in the rehabilitation setting require further examination so that patient outcomes may be improved. The purpose of this narrative review was to: (1) examine the defining characteristics of malnutrition, starvation, sarcopenia and cachexia; (2) review the validity of nutrition screening tools and nutrition assessment tools in the rehabilitation setting; and (3) determine the prevalence of malnutrition in the rehabilitation setting by geographical region and method of diagnosis. A narrative review was conducted drawing upon international literature. Starvation represents one form of malnutrition. Inadequate energy and protein intake are the critical factor in the aetiology of malnutrition, which is distinct from sarcopenia and cachexia. Eight nutrition screening tools and two nutrition assessment tools have been evaluated for criterion validity in the rehabilitation setting, and consideration must be given to the resources of the facility and the patient group in order to select the appropriate tool. The prevalence of malnutrition in the rehabilitation setting ranges from 14-65% worldwide with the highest prevalence reported in rural, European and Australian settings. Malnutrition is highly prevalent in the rehabilitation setting, and consideration must be given to the patient group when determining the most appropriate method of identification so that resources may be used efficaciously and the chance of misdiagnosis minimised.

  13. Nutritional support of the pediatric oncology patient.

    Science.gov (United States)

    Andrassy, R J; Chwals, W J

    1998-01-01

    The child with a malignancy frequently will have associated cachexia with significant weight loss and malnutrition. The reasons for this are multifactorial and may be related directly to the tumor, such as increased metabolic rate, circulating peptides leading to anorexia, and decreased intake due to poor appetite or gut involvement. There appears to be other reasons involved, including increased whole body protein breakdown, increased lipolysis, and increased gluconeogenesis. Release of certain cytokines, such as tumor necrosis factor, interleukin-1, interleukin-6, and others may increase the cancer cachexia. Malnutrition in these children leads to intolerance of chemotherapy and radiotherapy as well as increased local and systemic infections. For many years, oncologists were hesitant to provide nutrition support to cancer patients for fear that tumor growth would be enhanced. Pediatric oncologists learned early that starvation plays no positive role in cancer therapy. Adjunctive nutritional support, either enterally or parenterally, supports the patient during therapy with surgery, chemotherapy, or radiation. Many studies have now shown that the nutritionally replete patient tolerates therapy better and in some pediatric malignancies may enhance survival.

  14. [Nutrition and cancer patients].

    Science.gov (United States)

    Katsuramaki, T; Hirata, K; Isobe, M

    1998-03-01

    Nutritional therapy for cancer patients includes various objectives such as improvement of cachexia, elucidation of the mechanism of malnutrition, development of therapy for anorexia, nutrition support during chemotherapy or radiotherapy, and inhibition of tumor growth under controlled caloric intake. This review describes recent remarkable developments in nutritional therapy for cancer patients. Cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor which induce proteolysis and lipolysis are involved in the cause of malnutrition and cachexia in cancer patients. IL-1 also plays a significant role in the development of cancer anorexia via direct action in the brain. For anorexia therapy, progestogens have been shown to improve appetite and food intake in cancer patients. Moreover, glutamine supplementation improves the host protein metabolism without enhancement of tumor growth during chemotherapy. Among the effects of caloric intake on anticancer therapy, AO-90, a methionine-free intravenous amino acid solution, has been shown to increase the antitumor effect of 5-fluorouracil in clinical studies. From these observations, recent progress in nutritional therapy for cancer patients has been remarkable. Further study of nutritional therapy is required in order to maintain or improve the quality of life of cancer patients in the future.

  15. 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.

  16. The emerging roles of leptin and ghrelin in cardiovascular physiology and pathophysiology.

    Science.gov (United States)

    Sharma, Vijay; McNeill, John H

    2005-04-01

    Leptin and ghrelin are novel peptide hormones which are counter-regulatory in the central control of appetite. More recently, it has become clear that these hormones have a range of effects on the cardiovascular system. Leptin increases sympathetic activity, producing a pressor effect when acting on the central nervous system. However, leptin produces vasodilation by an endothelium-dependent mechanism peripherally. Ghrelin decreases sympathetic activity and has a depressor effect when acting on the central nervous system. Peripherally, ghrelin produces vasodilation by an endothelium-independent mechanism. Ghrelin improves left ventricular function and cardiac cachexia in heart failure. Leptin may contribute to cardiac cachexia, and to obesity-related cardiomyopathy by a variety of mechanisms. Leptin has pro-inflammatory, proliferative and calcification promoting effects in the vasculature. Ghrelin has recently been shown to be anti-inflammatory in the vasculature. Leptin may also produce a pro-thrombotic state through stimulation of platelet aggregation and inhibition of coagulation and fibrinolysis. The evidence for and against these effects as well as their pathophysiological significance in obesity hypertension, heart failure, atherosclerosis and thrombosis are discussed.

  17. A Dog with Multiple Infections of Enteric Parasitic Zoonosis in Mashhad City, North-East of Iran; a Case Report

    Directory of Open Access Journals (Sweden)

    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.

  18. Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by ERK inhibition.

    Directory of Open Access Journals (Sweden)

    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.

  19. Fiber type-specific nitric oxide protects oxidative myofibers against cachectic stimuli.

    Directory of Open Access Journals (Sweden)

    Zengli Yu

    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.

  20. Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii.

    Science.gov (United States)

    Arsenijevic, D; Girardier, L; Seydoux, J; Chang, H R; Dulloo, A G

    1997-05-01

    The temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain were examined in a mouse model of infection with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose onset coincided with elevated IL-2, and at the end of the acute phase of cachexia, the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma. In the chronic phase of the infection, the mice showed either partial weight recovery (gainers) or no weight regain (nongainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected nongainers continued to show both anoroxia and hypermetabolism, which were associated with elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial weight recovery.

  1. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN - a randomized multicentre trial

    Directory of Open Access Journals (Sweden)

    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.

  2. The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox.

    Science.gov (United States)

    Martinez-Outschoorn, Ubaldo E; Whitaker-Menezes, Diana; Pavlides, Stephanos; Chiavarina, Barbara; Bonuccelli, Gloria; Casey, Trimmer; Tsirigos, Aristotelis; Migneco, Gemma; Witkiewicz, Agnieszka; Balliet, Renee; Mercier, Isabelle; Wang, Chengwang; Flomenberg, Neal; Howell, Anthony; Lin, Zhao; Caro, Jaime; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P

    2010-11-01

    anti-cancer therapy that combines the alternating use of both autophagy promoters and autophagy inhibitors would be expected to prevent the onset of drug resistance. We also discuss why anti-angiogenic therapy has been found to promote tumor recurrence, progression and metastasis. More specifically, anti-angiogenic therapy would induce autophagy in the tumor stroma via the induction of stromal hypoxia, thereby converting a non-aggressive tumor type to a "lethal" aggressive tumor phenotype. Thus, uncoupling the metabolic parasitic relationship between cancer cells and an autophagic tumor stroma may hold great promise for anti-cancer therapy. Finally, we believe that autophagy in the tumor stroma is the local microscopic counterpart of systemic wasting (cancer-associated cachexia), which is associated with advanced and metastatic cancers. Cachexia in cancer patients is not due to decreased energy intake, but instead involves an increased basal metabolic rate and increased energy expenditures, resulting in a negative energy balance. Importantly, when tumors were surgically excised, this increased metabolic rate returned to normal levels. This view of cachexia, resulting in energy transfer to the tumor, is consistent with our hypothesis. So, cancer-associated cachexia may start locally as stromal autophagy, and then spread systemically. As such, stromal autophagy may be the requisite precursor of systemic cancer-associated cachexia.

  3. Change of the growth hormone-insulin-like growth factor-I axis in patients with gastrointestinal cancer: related to tumour type and nutritional status.

    Science.gov (United States)

    Huang, Qi; Nai, Yong-Jun; Jiang, Zhi-Wei; Li, Jie-Shou

    2005-06-01

    Changes in the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis, especially acquired GH resistance, develop in many severe illnesses, including cachexia. To study changes in the GH-IGF-I axis in patients with cancer cachexia, biochemical markers and body composition parameters were measured in eighty-eight gastric cancer patients, thirty colorectal cancer patients (subclassified according to the presence or absence of cachexia) and twenty-four healthy control subjects. Fifty-nine patients were defined as cachectic, based on the percentage of weight loss compared with their previous normal weight. The remaining fifty-nine patients were defined as non-cachectic. Measurements were repeated in twenty-seven patients (sixteen with gastric cancer and eleven with colorectal cancer) 3 months after radical operation. Compared with the controls, the cachectic gastric cancer patients had high GH levels (1.36 v. 0.32 ng/ml; P=0.001), a trend towards high IGF-I levels (223.74 v. 195.15 ng/ml; P=0.128 compared with non-cachectic patients) and a low log IGF-I/GH ratio (2.55 and 2.66 v. 3.00; P=0.002), along with a decreased BMI; the cachectic colorectal cancer patients showed the biochemical characteristics of acquired GH resistance: high GH (0.71 v. 0.32 ng/ml; P=0.016), a trend towards decreased IGF-I levels (164.18 v. 183.24 ng/ml; P=0.127) and a low log IGF-I/GH ratio (2.54 v. 2.99; P=0.005), with increased IGF-I levels following radical surgery (200.49 v. 141.91 ng/ml; P=0.046). These findings suggest that normal GH reaction and sensitivity occur in gastric cancer patients, controlled by nutritional status, whereas acquired GH resistance develops in cachectic colorectal cancer patients, which may be caused by tumour itself.

  4. 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

  5. An analysis of the association of gastroenteric lesions with chronic wasting syndrome of marmosets.

    Science.gov (United States)

    Chalifoux, L V; Bronson, R T; Escajadillo, A; McKenna, S

    1982-09-01

    Retrospective pathology data from necropsies of 162 marmosets, Saguinus oedipus, were studied to determine the nature of chronic wasting syndrome, a poorly defined entity associated with a high mortality rate in many marmoset colonies. Paraffin sections of the gastroenteric organs of 116 of these marmosets were re-examined in detail; lesions were identified, quantitated, and analyzed with a method of multiple chi-square testing for possible associations between findings. Five distinct disease entities were identified: prosthenorchosis, amebiasis, paramyxovirus disease, sepsis, and chronic colitis. Lesions of several of these often occurred in the same monkey, and all but the first were associated with cachexia. Lesions of chronic colitis were crypt abscesses, mononuclear and polymorphonuclear infiltration of the lamina propria, epithelial cell atypia, karyorrhexis, and lymphoid hyperplasia. The cause of chronic colitis was not identified, nor was any explanation found for weight loss and increased susceptibility to disease.

  6. Huntington's disease: review and anesthetic case management.

    Science.gov (United States)

    Cangemi, C F; Miller, R J

    1998-01-01

    Huntington's disease is a dominantly inherited progressive autosomal disease that affects the basal ganglia. Symptoms appear later in life and manifest as progressive mental deterioration and involuntary choreiform movements. Patients with Huntington's disease develop a progressive but variable dementia. Dysphagia, the most significant related motor symptom, hinders nutrition intake and places the patient at risk for aspiration. The combination of involuntary choreoathetoid movements, depression, and apathy leads to cachexia. Factors of considerable concern to the anesthesiologist who treats patients with Huntington's disease may include how to treat frail elderly people incapable of cooperation, how to treat patients suffering from malnourishment, and how to treat patients with an increased risk for aspiration or exaggerated responses to sodium thiopental and succinylcholine. The successful anesthetic management of a 65-yr-old woman with Huntington's disease who presented for full-mouth extractions is described.

  7. Retrieval-balloon-assisted enterography in post-pancreaticoduodenectomy endoscopic retrograde cholangiopancreatography post-pancreaticoduodenectomy

    Institute of Scientific and Technical Information of China (English)

    Ming Zhuang; Wen-Jie Zhang; Jun Gu; Ying-Bin Liu; Xue-Feng Wang

    2012-01-01

    This case reports an application of conventional duodenoscope in a post pancreaticoduodenectomy patient with the help of retrieval balloon assisted enterography.The 56-year-old woman had pancreaticoduodenectomy with Child reconstruction 9 mo ago because of pancreatic adenocarcinoma and now there are recurrent enlarged lymph nodes in the anastomotic stoma of hepaticojejunostomy.Considering the patient's late-stage cancer,a plastic stent was then successfully placed there to drainage.The main challenge in this case was the extremely long afferent loop and blind cannulation through the anastomotic stoma of hepaticojejunostomy.Retrieval balloon assisted enterography is very helpful for duodenoscope going through the reconstructed intestinal tract and for the cannulation.After two weeks,the patient remained free of painful symptoms and free of fever.Liver function improved well.Four months after the placement of stent,the patient died of cachexia without jaundice,fever and abdominal pain according to her daughter's statement.

  8. Modulating the endocannabinoid system in human health and disease--successes and failures.

    Science.gov (United States)

    Pacher, Pál; Kunos, George

    2013-05-01

    The discovery of the endocannabinoid system, comprising the G-protein coupled cannabinoid 1 and 2 receptors (CB1/2), their endogenous lipid ligands or endocannabinoids, and synthetic and metabolizing enzymes, has triggered an avalanche of experimental studies implicating the endocannabinoid system in a growing number of physiological/pathological functions. These studies have also suggested that modulating the activity of the endocannabinoid system holds therapeutic promise for a broad range of diseases, including neurodegenerative, cardiovascular and inflammatory disorders; obesity/metabolic syndrome; cachexia; chemotherapy-induced nausea and vomiting; and tissue injury and pain, amongst others. However, clinical trials with globally acting CB1 antagonists in obesity/metabolic syndrome, and other studies with peripherally-restricted CB1/2 agonists and inhibitors of the endocannabinoid metabolizing enzyme in pain, have introduced unexpected complexities, suggesting that a better understanding of the pathophysiological role of the endocannabinoid system is required to devise clinically successful treatment strategies.

  9. Alveolar rhabdomyosarcoma of the sphenoid sinus mimicking optic neuritis presenting with intermittent visual loss in an adult

    Science.gov (United States)

    Liu, Wendong; Jiang, Libin; Jin, Yulan; Yang, Bentao; Lai, Timothy YY

    2016-01-01

    A 23-year-old male with intermittent visual loss in his left eye for 4 months was originally treated as optic neuritis elsewhere. Upon presentation to our hospital (Beijing Tongren Hospital), his left eye visual acuity was reduced to hand motion at face. The left eye ocular motility was limited in upgaze, downgaze, adduction, and abduction. Computed tomography and magnetic resonance imaging revealed lesions in the sphenoid and ethmoid sinuses, orbital apex and carvernous sinus invading adjacent extraocular muscles. Endoscopic ethmo-sphenoidostomy and debulking surgery was performed and histopathology of the specimen demonstrated alveolar rhabdomyosarcoma. Despite having treatment with a combination of orbital radiation therapy and systemic chemotherapy, the patient developed generalized metastasis with cachexia and the left eye became no light perception due to optic atrophy. PMID:27932889

  10. Brucellar sternoclavicular arthritis, the forgotten complication.

    Science.gov (United States)

    Mousa, A M; Muhtaseb, S A; Al-Mudallal, D S; Marafie, A A; Habib, F M

    1988-06-01

    Of 511 cases of brucellosis studied between December 1983 and February 1986, four (0.8%) had sternoclavicular (STCL) arthritis. Two were male and two female, and only one was younger than 50 years old. All four cases had significantly high specific IgG antibody titres (1 of 1280), measured by the indirect immunofluorescent (IIF) test, and two had Brucella melitensis isolated from their blood. In two cases, STCL arthritis was the presenting problem, and it was associated in one with ankle arthritis, hepatitis, renal impairment, orogenital ulcers and a haematological picture of myelodysplasia; in the other it was a relapsing STCL arthritis. In the remaining two cases, STCL arthritis was part of an extensive osteoarticular disease, which was associated in one with cachexia, liver cirrhosis, heart failure and prostatitis with urine retention, and in the other with severe thrombocytopenia. Excellent results were obtained from six to eight weeks' therapy with streptomycin, rifampicin and cotrimoxazole or tetracycline.

  11. Review of novel aspects of the regulation of ghrelin secretion.

    Science.gov (United States)

    Al Massadi, Omar; Lear, Pamela V; Muller, Timo D; Lopez, Miguel; Dieguez, Carlos; Tschop, Matthias H; Nogueiras, Ruben

    2014-01-01

    The role of ghrelin in regulating metabolism and energy balance has been a subject of intense focus ever since its discovery. Ghrelin regulates energy balance in the short term by induction of appetite and in the longer term by increasing body weight and adiposity. It is the only known peripheral orexigenic hormone and one of the most potent endogenous orexigenic factors discovered to date. However, whilst extensively studied, the mechanism of ghrelin secretion is not well understood. A better understanding of the pathways controlling ghrelin secretion could be useful in the development of new therapeutic approaches to appetite-related disorders. Here, we discuss current knowledge of the processes that control ghrelin secretion, focusing on neural, chemical and hormonal stimuli. In addition, we share our view on the potential of targeting ghrelin for the treatment of eating disorders such as obesity, anorexia nervosa and cachexia.

  12. Rikkunshito and ghrelin secretion.

    Science.gov (United States)

    Takeda, Hiroshi; Muto, Shuichi; Nakagawa, Koji; Ohnishi, Shunsuke; Asaka, Masahiro

    2012-01-01

    Rikkunshito is a kampo herbal medicine which is widely used in Japan for the treatment of the upper gastrointestinal symptoms of patients with functional dyspepsia (FD), gastroesophageal reflux disease (GERD), dyspeptic symptoms of postgastrointestinal surgery patients, and chemotherapy-induced dyspepsia in cancer patients. Recently, very unique characteristics of rikkunshito have been unveiled; oral administration of rikkunshito potentiates orexigenic action of ghrelin through several different mechanisms. In addition, several lines of evidence obtained from both animal and human studies indicate that rikkunshito can be an attractive and promising therapeutic option for the anorectic conditions including cisplatin-induced dyspepsia, anorexia of aging, stress-induced hypophagia, cancer cachexia-anorexia syndrome. In this review, we will highlight what is known about the orexigenic effect of rikkunshito with a special focus on an interaction with ghrelin signaling system.

  13. Isolation of avian serotype 3 paramyxoviruses from imported caged birds in Israel.

    Science.gov (United States)

    Shihmanter, E; Weisman, Y; Lublin, A; Mahani, S; Panshin, A; Lipkind, M

    1998-01-01

    Ten avian serotype 3 paramyxoviruses were isolated for the first time in Israel from passerine and psittacine imported caged birds. The birds were submitted for investigation of an illness characterized by nonspecific signs of weakness, anorexia, vomiting, and sneezing. In addition, only the parakeets developed specific neurologic signs. In bacteriologic and pathologic investigation, cachexia and diarrhea were observed in both groups of birds. In psittacines, considerable alterations were observed in lungs, liver, and spleen. Some nonviral pathogens were occasionally isolated. The isolates appeared to belong to serotype 3b avian paramyxovirus (APMV), the prototype strain of which is APMV-3b/parakeet/Netherlands/449/75. The isolation of APMV-3 viruses from imported caged birds may represent a way of introduction of these viruses into the country.

  14. [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.

  15. General Survey and Progress in Clinical Trials Abroad over Kanglaite Injection(康莱特注射液)

    Institute of Scientific and Technical Information of China (English)

    李大鹏

    2004-01-01

    @@ Kanglaite (康莱特, KLT) is made of a lipolytic and efficacious anti-cancer ingredient isolated from Chinese herb Semen Coix lacryma-jobi, an anti-cancer emulsion made with international advanced technology for intravenous and intra-arterial injection, which has obvious efficacy in treating many primary malignant tumors such as lung cancer, liver cancer, gastric cancer, breast cancer etc.and could markedly elevate immune function, as it is a biphasic broad spectrum anti-cancer agent;KLT combined with radiotherapy or chemotherapy could alleviate toxicity and raise their efficacy, and before surgical operation could facilitate cancer cell necrosis, apoptosis, prevent diffusion and metastasis, effectively act against cachexia, control cancer pain, increase body weight, improve quality of life and extend survival period of cancer patients in the advanced stage. Since came to market, KLT has been used in over 2 000 large and medium hospitals at home, and 300 000 cancer patients have benefited clinically from it.

  16. Effect of early psychological intervention on patients with advanced tumors%晚期恶性肿瘤早期心理干预的疗效观察

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ Background: To the terminal stages of esophagus cancer without chance of surgery, radiotherapy has unsatisfactory effect either. It is difficult to swallow for the patients, of whom some even cannot eat anything and lose their weight gradually, and finally, lose the ability to take care of themselves. Even if their lives can be maintained, their life quality is very low. In order to alleviate dysphasia, we have carried out the chemotherapy schemes of CMP and DMB. Objective: By means of united chemotherapy, the following effects are expected: to reduce the focus, to improve the ability to take food, to recover from cachexia, and to reach the target of improving the patients' life quality. Design: Treat the terminal stages of esophagus cancer with united chemotherapy and evaluate the effect in time. Unit: PLA 323 Hospital.

  17. Drug/Nutrients Interaction in Neoplastic Patients Requiring Nutritional Support. Practical Advice with Special Focusing on Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ilaria Uomo

    2008-07-01

    Full Text Available Malnutrition and cachexia are frequent complaints in neoplastic disease [1, 2]. Nutritional support and pain treatment still remain the main treatment option for the majority of patients with cancer, particularly for those affected by pancreatic cancer who very often present an advanced stage of the disease at moment of first diagnosis [3, 4, 5]. Therefore, in their clinical practice, physicians are faced with the need for parenteral or enteral nutrition and with the contemporary requirement of several drugs capable of interfering with the components of the nutritional admixture. Different drawbacks may arise from these drug/nutrient interactions, nullifying the pharmacological effect and/or the nutritional value [6]. The aim of this review is to summarize possible drug/nutrient interaction in neoplastic patients, particularly in those with pancreatic cancer, during external food supplementation.

  18. Leptin-activity blockers: development and potential use in experimental biology and medicine.

    Science.gov (United States)

    Gertler, Arieh; Solomon, Gili

    2013-11-01

    The first adipokine, leptin, discovered almost 20 years ago, is secreted into circulation mainly from adipose tissue and acts both centrally and peripherally. Leptin regulates energy metabolism, reproductive function, bone metabolism, and immune response. However in some physiological or pathological situations such as enhancement of undesired immune responses in autoimmune diseases, tumorigenesis, elevated blood pressure, and certain cardiovascular pathologies, leptin activity may be harmful. In this review we screen different approaches to blocking leptin action, in vitro and in vivo. The recent development of superactive leptin muteins exhibiting antagonistic properties, and other leptin-action-blocking peptides, proteins, monoclonal antibodies, and nanobodies, opens new perspectives for their use in research, and eventually, therapy for cachexia, autoimmune disease, cancer, and other pathologies.

  19. Macroglossia in acromegaly and hypothyroidism.

    Science.gov (United States)

    Wittmann, A L

    1977-04-29

    The tongues of two patients with macroglossia were examined at autopsy. One of the patients had acromegaly and the other had hypothyroidism. To evaluate the size of the enlarged tongues, the average weight of the tongue in the human adult was determined first in a series of 20 unselected autopsies, 10 males and 10 females (ages 44 to 85). The weight of the tongue was greater in males than in females and was directly correlated with the height of the subject. Cachexia had relatively little effect on the weight. In acromegaly (case 21) and myxedema (case 22) the tongue was enlarged by at least 50%. Histopathology showed enlargement of muscle fibers especially anteriorly in acromegaly and hypothyroidism, thickening of the epithelium and increased subepithelial and interstitial connective tissue. Incidental findings included venous thrombi and telangiectasia in the subepithelial connective tissue in both hypothyroidism and acromegaly and a corpus amylaceum and two islands of hyaline cartilage in the tongue of hypothyroidism.

  20. First isolation and nucleotide comparison of the gag gene of the caprine arthritis encephalitis virus circulating in naturally infected goats from Argentina

    Directory of Open Access Journals (Sweden)

    Carlos Javier Panei

    2017-02-01

    Full Text Available 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 detected by serology, it has never been isolated or characterized. Thus, the objectives of this work were to isolate and analyze the nucleotide sequences of the gag gene of Argentine CAEV strains and compare them with those of other SRLVs previously reported. Nucleotide sequence comparison showed homology with CAEV-Co, the CAEV prototype. Phylogenetic analyses showed that the Argentine strains clustered with genotype B, subtype B1. Because the molecular characterization of the gag region is suitable for phylogenetic studies and may be applied to monitor the control of SRLV, molecularly characterizing the Argentine CAEV strains may help develop a proper plan of eradication of CAEV infections.

  1. Anabolic treatment with GH, IGF-I, or anabolic steroids in patients with HIV-associated wasting.

    Science.gov (United States)

    Mulligan, Kathleen; Schambelan, Morris

    2002-09-01

    Wasting, and particularly loss of metabolically active lean tissue, contributes to increased mortality, accelerated disease progression, and impairment of strength and functional status in patients with HIV infection. A variety of protein anabolic agents, including growth hormone, insulin-like growth factor-I, testosterone, nandrolone decanoate, oxandrolone, and oxymetholone, have been studied in patients with HIV-associated wasting. Overall, these studies have demonstrated that treatment with protein anabolic agents can increase lean body mass (LBM) and in some cases provide functional benefits and improvements in quality of life. Further research is needed to determine whether such treatment prolongs survival or reduces the overall health care burden of HIV infection. The advances in identification of successful treatments for HIV-associated wasting can provide a model for using these therapies in other catabolic states, including end-stage renal disease, cancer, chronic obstructive pulmonary disease, and cardiac cachexia.

  2. Treatment of refractory hemodialysis ascites with maintenance peritoneal dialysis.

    Science.gov (United States)

    Ing, T S; Daugirdas, J T; Popli, S; Kheirbek, A O; Humayun, H M; Gandhi, V C; Chapa, S M

    1981-04-01

    In 5 patients who were receiving maintenance hemodialysis, ascites developed that was refractory to treatment by ultrafiltration during hemodialysis. Use of sequential isolated ultrafiltration and hemodialysis therapy either precipitated side effects or else required prolongation of total treatment time which the patients declined to accept. In 4 of the patients, ascites was believed to be primarily responsible for severe, progressive cachexia. Maintenance peritoneal dialysis was instituted in all patients, and abdominal fluid was removed gradually, over a period of 2 to 3 days. Ascites resolved promptly in each case. Three patients noted a dramatic improvement in appetite after relief of abdominal distension. Follow-up periods ranged from 6 to 4 1/2 years. Our results suggest that maintenance peritoneal dialysis can successfully control hemodialysis ascites.

  3. MRI demonstration of orbital lipolysis in anorexia nervosa

    Energy Technology Data Exchange (ETDEWEB)

    Demaerel, Philippe; Dekimpe, Piet; Wilms, Guy [Department of Radiology, University Hospitals, Herestraat 49, 3000 Leuven (Belgium); Muls, Erik [Department of Endocrinology, University Hospitals, Herestraat 49, 3000 Leuven (Belgium)

    2002-07-01

    The purpose of this article is to describe the orbital changes due to lipolysis in anorexia nervosa. We examined a cachectic patient with MR imaging using T1-weighted images before and after contrast enhancement. Orbital fat edema has been observed in extreme forms of cachexia and the CT and MR findings have recently been reported. The imaging appearances have been explained by the disappearance of the fat tissue and the appearance of edema due to a disturbance in the electrolyte fluid balance. In the recent literature particular attention has been paid to the increased lipid peroxidation and lipolysis in anorexia nervosa. These metabolic processes result in an increased permeability of the vessel wall endothelium, which can explain the extravasation of the contrast agent in the orbital fat on MR imaging. (orig.)

  4. 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.

  5. 晚期恶性肿瘤患者157例营养治疗临床分析%A clinical analysis of nutritional therapy in 157 cases with advanced malignancy

    Institute of Scientific and Technical Information of China (English)

    Jun Liang; Shaobai Li; Baofang Bao; Qun Yin

    2011-01-01

    Objective: The aim of this study was to evaluate clinical efficacy of nutritional therapy with Kabiven PI and ω-3 fish oil fat emulsion on advanced stage of malignant tumor. Methods: One hundred and fifity-seven patients with advanced stage of malignant tumor were performed parenteral nutrition and enteral nutritional adjunctive therapy with Kabiven PI and ECOG ≥ 3 of 103 cases, therapy interval 2-3 weeks, declined 1 score. 28 were performed with chemotherapeutics under nutritional therapy 2-4 periodical. 25 of 26 died were dead for cancer cachexia and multiple organ failure. Survival time was 2-7 months. No serious complications occurred in all patients. Conclusion: The symptom and quality of life of advanced stage of malignant tumor were obviously improve by nutritional therapy. The opportunity for therapy tumor was offered. It is a important method on combined therapy of malignant tumor.

  6. Primary yolk sac tumor of seminal vesicle: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Yao Xu-Dong

    2012-09-01

    Full Text Available Abstract Background Yolk sac tumor (endodermal sinus tumor is a rare malignant germ cell tumor arising in the testis or ovary. Extragonadal yolk sac tumor is even rarer and has only been described in case reports. Due to the rarity of the tumors, the appropriately optimal treatment remains unclear. We report a case of yolk sac tumor in the seminal vesicle. Case A 38-year-old Asian male presented with gross hematuria and hemospermia. Transrectal ultrasound scan showed a solid mass in the left seminal vesicle and the scrotal sonography showed no abnormalities. Bilateral seminal vesicles were resected, and histopathological examination showed a typical pattern of yolk sac tumor (YST. The patient responded poorly to comprehensive treatment of radiotherapy, chemotherapy and surgeries, developed systemic multiple metastases, and died of cachexia one and half years after diagnosis.

  7. 十全大补汤对中晚期胃肠道肿瘤患者生活质量的影响

    Institute of Scientific and Technical Information of China (English)

    蔡红兵; 徐舒; 余志坚; 李洪; 李滨

    2008-01-01

    中晚期胃肠道恶性肿瘤患者经常出现食欲不振和恶病质(cancer anorexia—cachexia syndrome,CACS),加上接受放、化疗,会出现不同程度的消化道及全身副反应。严重影响患者的生活质量和接受治疗的耐受性。2006-10-2008—03,我们运用十全大补汤为主方配合治疗晚期消化道肿瘤47例,现报告如下。

  8. Pharmacokinetics of drugs in cachectic patients: a systematic review.

    Directory of Open Access Journals (Sweden)

    Katja Trobec

    Full Text Available Cachexia is a weight-loss process caused by an underlying chronic disease such as cancer, chronic heart failure, chronic obstructive pulmonary disease, or rheumatoid arthritis. It leads to changes in body structure and function that may influence the pharmacokinetics of drugs. Changes in gut function and decreased subcutaneous tissue may influence the absorption of orally and transdermally applied drugs. Altered body composition and plasma protein concentration may affect drug distribution. Changes in the expression and function of metabolic enzymes could influence the metabolism of drugs, and their renal excretion could be affected by possible reduction in kidney function. Because no general guidelines exist for drug dose adjustments in cachectic patients, we conducted a systematic search to identify articles that investigated the pharmacokinetics of drugs in cachectic patients.

  9. Exercise Intensity Modulation of Hepatic Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Fábio S. Lira

    2012-01-01

    Full Text Available Lipid metabolism in the liver is complex and involves the synthesis and secretion of very low density lipoproteins (VLDL, ketone bodies, and high rates of fatty acid oxidation, synthesis, and esterification. Exercise training induces several changes in lipid metabolism in the liver and affects VLDL secretion and fatty acid oxidation. These alterations are even more conspicuous in disease, as in obesity, and cancer cachexia. Our understanding of the mechanisms leading to metabolic adaptations in the liver as induced by exercise training has advanced considerably in the recent years, but much remains to be addressed. More recently, the adoption of high intensity exercise training has been put forward as a means of modulating hepatic metabolism. The purpose of the present paper is to summarise and discuss the merit of such new knowledge.

  10. 益气健脾法治疗癌症恶病质临床观察

    Institute of Scientific and Technical Information of China (English)

    金军

    2011-01-01

    癌症恶病质(cancer cachexia)是指由于癌症进展而出现的体质量下降、厌食及衰竭三联征[1].癌症晚期约50%、终末期约80%发生恶病质,在老年患者及儿童更为常见,并随进程而加重,严重影响患者的生活质量,缩短生存期,是大多数中晚期癌症患者所面临的主要问题.笔者采用益气健脾法治疗癌症恶病质取得较好疗效,现总结报道如下.

  11. Paraneoplastic endocrine-metabolic syndromes

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. On Biology as an Emergent Science

    CERN Document Server

    Noyes, H Pierre

    2007-01-01

    Biology is considered here as an "emergent science" in the sense of Anderson and of Laughlin and Pines. It is demonstrated that a straightforward mathematical definition of "biological system" is useful in showing how biology differs in structure from the lower levels in Anderson's "More is Different" hierarchy. Using cells in a chemostat as a paradigmatic exemplar of a biological system, it is found that a coherent collection of metabolic pathways through a single cell in the chemostat also satisfies the proposed definition of a biological system. This provides a theoretical and mathematical underpinning for Young's fundamental model of biological organization and integration. Evidence for the therapeutic efficacy of Young's method of analysis is provided by preliminary results of clinical trials of a specific application of Young's model to the treatment of cancer cachexia.

  14. The effect of serum insulin like factor Ⅰ on mouse cancer%血清胰岛素样生长因子-1影响小鼠肿瘤模型的实验研究

    Institute of Scientific and Technical Information of China (English)

    张珊; 陈国庆; 唐泓波; 马士辉; 高峰; 吴毅平

    2008-01-01

    目的 探讨血清胰岛素样生长因子-1(IGF-1)水平对小鼠肿瘤模型的影响.方法 用小鼠结肠腺癌CT26细胞接种于肝特异性IGF-1基因缺失鼠[LID]及对照组小鼠皮下,共120只6周龄的雄鼠接受了肿瘤移植,其中对照鼠和LID鼠各60只.2组小鼠分别又随机分成2个亚组(每个亚组各30只小鼠).一个亚组每10只分别在肿瘤移植后第10,14,18天开始每天一次接受皮下注射重组人GH(1 mg/kg)至第22天结束;另一个亚组接受盐水注射.结果 接受GH注射的LID和对照鼠血清IGF-1均升高.从第10天开始干预时,高水平的IGF-1促进恶病质形成.从第14开始干预时,血清IGF-1水平与小鼠恶病质状态呈负相关.18 d则效果不明显.结论 肿瘤早期,IGF-1,GH加快肿瘤生长,促进恶病质形成.当恶病质已形成时,早期干预则可以改善之.%Objective To determine the effect of different serum insulin-like growth factor-Ⅰ(IGF-1)levels on mouse cancer.Methods A total of 120 male mice at 6 weeks of age(60 control mice and 60 LID mice)were subcutaneously injected colon tumor CT26 cell line.Each group was random divided into two subgroups respectively,every 10 mice of one subgroup were injected subcutaneously with growth hormone(GH)(1ms/kg)daily from the 10th,14th and18th days respectively until the 22nd days,and the other subgroup received saline injection.Results All mice treated with GH have higher level of IGF-1,compared with those treated with saline.High level of IGF-1 promoted the development of cachexia in these mice treated with GH from the 10th days.However,the level of IGF-1 has negative correlation with the cancer cachexia state for mice treated with GH from the 14th days.Conclusion Circulating IGF-1 and GH play an important role in tumor growth 4nd cachexia development in the early stage of cancer and can ameliorate the state of cachexia in the advanced stage.

  15. 健脾化痰汤治疗癌症恶病质40例

    Institute of Scientific and Technical Information of China (English)

    李佑民; 李成银

    2011-01-01

    @@ 癌症恶病质(cancer cachexia, CC),又称癌性恶液质,主要是由肿瘤细胞产物及机体释放的细胞因子引起以全身三大物质代谢紊乱为特征的一种继发性反应[1],是癌症进展而出现的体重下降、厌食及衰竭三联征[2].迄今,现代医学尚缺乏能够有效控制CC进展的手段,因而给中医药疗法的应用治疗留下很大的发展空间.2010年1月-2010年12月,笔者采用健脾化痰汤治疗CC 40例,总结报道如下.

  16. 代谢介质在癌性恶病质中的作用及其机制

    Institute of Scientific and Technical Information of China (English)

    沈永华; 邹晓平

    2011-01-01

    恶病质目前没有明确的定义,一般认为是一种进行性的消耗状态,多见于威胁生命疾病的晚期,如恶性肿瘤、艾滋病、慢性阻塞性肺疾病、慢性肾衰竭等.大约50%的恶性肿瘤患者会出现癌性恶病质(cancer cachexia,CC),其中20%直接死于CC[1].CC降低生活质量并缩短生存期,给这类病人带来极大危害,其发病机制尚不清楚,但一般认为是多因素的.

  17. Hormonal Regulators of Appetite

    Directory of Open Access Journals (Sweden)

    Juliana Austin

    2009-01-01

    Full Text Available Obesity is a significant cause of morbidity and mortality worldwide. There has been a significant worsening of the obesity epidemic mainly due to alterations in dietary intake and energy expenditure. Alternatively, cachexia, or pathologic weight loss, is a significant problem for individuals with chronic disease. Despite their obvious differences, both processes involve hormones that regulate appetite. These hormones act on specific centers in the brain that affect the sensations of hunger and satiety. Mutations in these hormones or their receptors can cause substantial pathology leading to obesity or anorexia. Identification of individuals with specific genetic mutations may ultimately lead to more appropriate therapies targeted at the underlying disease process. Thus far, these hormones have mainly been studied in adults and animal models. This article is aimed at reviewing the hormones involved in hunger and satiety, with a focus on pediatrics.

  18. Hormonal Regulators of Appetite

    Directory of Open Access Journals (Sweden)

    Austin Juliana

    2008-11-01

    Full Text Available Obesity is a significant cause of morbidity and mortality worldwide. There has been a significant worsening of the obesity epidemic mainly due to alterations in dietary intake and energy expenditure. Alternatively, cachexia, or pathologic weight loss, is a significant problem for individuals with chronic disease. Despite their obvious differences, both processes involve hormones that regulate appetite. These hormones act on specific centers in the brain that affect the sensations of hunger and satiety. Mutations in these hormones or their receptors can cause substantial pathology leading to obesity or anorexia. Identification of individuals with specific genetic mutations may ultimately lead to more appropriate therapies targeted at the underlying disease process. Thus far, these hormones have mainly been studied in adults and animal models. This article is aimed at reviewing the hormones involved in hunger and satiety, with a focus on pediatrics.

  19. Dietetic management in gastrointestinal complications from antimalignant chemotherapy.

    Science.gov (United States)

    Calixto-Lima, L; Martins de Andrade, E; Gomes, A P; Geller, M; Siqueira-Batista, R

    2012-01-01

    Antineoplastic chemotherapy (CT) represents the systemic treatment of malignant tumors. It can be used alone or combined with surgery and / or radiotherapy. The cytotoxic agents used in chemotherapy work on both cancerous cells and noncancerous cells of the body, generally resulting in high toxicity. The biological aggressiveness of chemotherapy particularly affects rapidly replicating cells, such as those of the digestive tract, resulting in adverse effects that impair food intake, leading to compromised nutritional status and which may lead to cachexia. The main toxic effects of chemotherapy in the gastrointestinal tract include nausea, vomiting -these are the most frequent- constipation, diarrhea, xerostomia, mucositis, dysphagia and anorexia. Given the high frequency of such effects, nutritional intervention should be an integral part of cancer treatment, to maintain and/or improve the patient's nutritional status and reduce or minimize the side effects caused by treatment. Accordingly, the goal of this study is to review dietetic conduct in the process of caring for patients undergoing cancer chemotherapy.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. [Nutrition and fluid management in palliative medicine: do food and drink keep body and soul together?].

    Science.gov (United States)

    Gaser, E; Meissner, W

    2012-01-01

    Induction, implementation and continuation of an invasive nutrition or fluid administration in patients with advanced, life-limiting illnesses is an often controversial but also very emotionally discussed topic. This article summarizes the current state of knowledge based mainly on the European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines and is intended as a simple guide for clinical practice. In the early phase of disease the induction of an invasive food and fluid administration may be indicated in order to prevent undernutrition and cachexia, to enhance compliance with anti-tumor treatment, to control some adverse effects of anti-tumor therapy and to improve the quality of life. If oral or enteral feeding is possible this should be preferred. Patients in the final stage of a disease rarely suffer from hunger or thirst. In this phase of the disease other things, such as monitoring of patients and relatives play a much more important role.

  7. A practical approach to nutritional support for patients with advanced cancer.

    Science.gov (United States)

    Hill, D; Hart, K

    2001-07-01

    Palliative care can last from a few days to months and, in some cases, years. Consequently the nutritional needs of palliative care patients also vary, as does the extent to which nutrition intervention is pursued. Anorexia and cachexia are common side-effects of advanced cancer. They are characterized by physical depletion of the patients and an emotional drain on them, their families and carers. Pulling together the practical aspects of nutrition support and the emotional and social significance of food requires a skillful practitioner; an experienced dietitian can be a valued member of the palliative care team. This article examines the role of nutrition support in the palliative care setting, focusing upon practical advice including food modification, the use of oral supplements and enteral feeding.

  8. Benefits of Exercise in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    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.

  9. 癌性恶病质

    Institute of Scientific and Technical Information of China (English)

    徐富; 常瑛

    2000-01-01

    癌性恶病质(cancer cachexia,CAC)是指恶性肿瘤病人以进行性消瘦、体重明显减轻、厌食、乏力等为主要表现的一组综合征。其发生率从淋巴瘤的31%到胃癌的87%,晚期癌病人80%以上发生 CAC,而有些病人在肿瘤早期就出现体重明显减轻,或以此为首发症状而到医院就诊。CAC 是癌病人死亡的常见原因。1 CAC 的发病原因CAC 的病因尚未完全清楚,一般认为是多种因素共

  10. 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.

  11. Treatment of Cancer Pain by Targeting Cytokines.

    Science.gov (United States)

    Vendrell, I; Macedo, D; Alho, I; Dionísio, M R; Costa, L

    2015-01-01

    Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be related to cancer pain. Nevertheless, in some cases, targeted drugs are available and in use for other diseases. In this paper, we aim to review the importance of cytokines in cancer pain and targeted strategies that can have an impact on controlling this symptom.

  12. TNF — EDRN Public Portal

    Science.gov (United States)

    TNF (tumor necrosis factor) is a cytokine involved in many biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. TNF belongs to the TNF superfamily. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. TNF binds to its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR, through which it functions. It is involved in cellular responses to stimuli such as cytokines and stress and plays a key role in regulating the immune response to infection. This cytokine is a pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia. TNF has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggest this cytokine has a neuroprotective function. TNF is cleaved into two chains, tumor necrosis factor, membrane form and tumor necrosis factor, soluble form.

  13. Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part I.

    Science.gov (United States)

    Aikawa, Katsuji; Miyawaki, Toshio; Hitaka, Takenori; Imai, Yumi N; Hara, Takahito; Miyazaki, Junichi; Yamaoka, Masuo; Kusaka, Masami; Kanzaki, Naoyuki; Tasaka, Akihiro; Shiraishi, Mitsuru; Yamamoto, Satoshi

    2015-05-15

    To develop effective drugs for hypogonadism, sarcopenia, and cachexia, we designed, synthesized, and evaluated selective androgen receptor modulators (SARMs) that exhibit not only anabolic effects on organs such as muscles and the central nervous system (CNS) but also neutral or antagonistic effects on the prostate. Based on the information obtained from a docking model with androgen receptor (AR), we modified a hit compound A identified through high-throughput screening. Among the prepared compounds, 1-(4-cyano-1-naphthyl)-2,3-disubstituted pyrrolidine derivatives 17h, 17m, and 17j had highly potent AR agonistic activities in vitro and good tissue selectivity in vivo. These derivatives increased the weight of the levator ani muscle without influencing the prostate and seminal vesicle. In addition, these compounds induced sexual behavior in castrated rats, indicating that the compounds could also act as agonists on the CNS.

  14. An open label randomized multicentre phase IIIb trial comparing parenteral substitution versus best supportive nutritional care in subjects with pancreatic adenocarcinoma receiving 5-FU plus oxaliplatin as 2nd or higher line chemotherapy regarding clinical benefit - PANUSCO

    Directory of Open Access Journals (Sweden)

    Rötzer Ingeborg

    2009-11-01

    Full Text Available Abstract Background Pancreatic cancer is an extremely aggressive malignancy. Subjects are afflicted with a variety of disconcerting symptoms, including profound cachexia. Recent data indicate that the outcome of oncological patients suffering from cancer cachexia could be improved by parenteral nutrition and that parenteral nutrition results in an improvement of quality of life and in prolonged survival. Currently, there is no recommendation of routine use of parenteral nutrition. Furthermore, there is no clear recommendation for 2nd line therapy (or higher for pancreatic adenocarcinoma but often asked for. Methods/Design PANUSCO is an open label, controlled, prospective, randomized, multicentre phase IIIb trial with two parallel arms. All patients will be treated with 5-fluorouracil, folinic acid and oxaliplatin on an outpatient basis at the study sites. Additionally, all patients will receive best supportive nutritional care (BSNC. In the experimental group BSNC will be expanded with parenteral nutrition (PN. In contrast, patients in the control group obtain solely BSNC. Parenteral nutrition will be applied overnight and at home by experienced medical staff. A total of 120 patients are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to event-free survival (EFS, defined as the time from randomization till time to development of an event defined as either an impairment (change from baseline of at least ten points in EORTC QLQ-C30, functional domain total score or withdrawal due to fulfilling the special defined stopping criteria for chemotherapy as well as for nutritional intervention (NI or death from any cause (whichever occurs first. Discussion The aim of this clinical trial is to evaluate whether parenteral nutrition in combination with defined 2nd line or higher chemotherapy has an impact on quality of life for patients suffering from pancreatic adenocarcinoma. Trial registration Current

  15. Role of lipid peroxidation and antioxidant enzymes in omega 3 fatty acids induced suppression of breast cancer xenograft growth in mice

    Directory of Open Access Journals (Sweden)

    Cameron Ivan L

    2002-07-01

    Full Text Available Abstract Background Supplementing mice with high levels of dietary n-3 polyunsaturated fatty acids (PUFAs increases the n-3 PUFAs in cell membranes, increases the susceptibility of the cells for lipid peroxidation (LPO and decreases the growth rate of mammary and other tumors. However, the results of an earlier study indicated that a factor in addition to LPO was involved in the reduction in tumor growth in n-3 PUFAs fed mice. Athymic mice bearing MDA-MB-231 human breast carcinoma xenografts, were fed fish oil concentrate (FOC or control diets, with and without supplemental Vitamin E (2000 IU /kg diet and were sacrificed both before and after doxorubicin (DOX treatment to evaluate factors involved in tumor growth suppression. Results Prior to DOX, basal LPO in the tumor of 3% FOC fed mice was slightly higher than in the control fed mice and was decreased in mice consuming FOC with vitamin E. Vitamin E suppressed the DOX induced increase in LPO in the tumors of control mice, however, vitamin E was not sufficient to suppress a DOX induced increase in LPO in the tumors of FOC fed mice. The mean growth rate of tumors of FOC fed mice was significantly less than the mean growth rate of the tumors of control mice. Multiple regression analyses indicated that suppression of glutathione peroxidase (GPX activity by FOC prior to DOX therapy was more important than increased LPO as an explanation of tumor growth suppression. Tumor induced cachexia was decreased in mice consuming FOC. Conclusions It appears that the increased sensitivity to DOX was related to an FOC induced reduction in GPX activity. FOC reduced tumor induced cachexia.

  16. Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1.

    Science.gov (United States)

    Ruud, Johan; Nilsson, Anna; Engström Ruud, Linda; Wang, Wenhua; Nilsberth, Camilla; Iresjö, Britt-Marie; Lundholm, Kent; Engblom, David; Blomqvist, Anders

    2013-03-01

    It is well-established that prostaglandins (PGs) affect tumorigenesis, and evidence indicates that PGs also are important for the reduced food intake and body weight loss, the anorexia-cachexia syndrome, in malignant cancer. However, the identity of the PGs and the PG producing cyclooxygenase (COX) species responsible for cancer anorexia-cachexia is unknown. Here, we addressed this issue by transplanting mice with a tumor that elicits anorexia. Meal pattern analysis revealed that the anorexia in the tumor-bearing mice was due to decreased meal frequency. Treatment with a non-selective COX inhibitor attenuated the anorexia, and also tumor growth. When given at manifest anorexia, non-selective COX-inhibitors restored appetite and prevented body weight loss without affecting tumor size. Despite COX-2 induction in the cerebral blood vessels of tumor-bearing mice, a selective COX-2 inhibitor had no effect on the anorexia, whereas selective COX-1 inhibition delayed its onset. Tumor growth was associated with robust increase of PGE(2) levels in plasma - a response blocked both by non-selective COX-inhibition and by selective COX-1 inhibition, but not by COX-2 inhibition. However, there was no increase in PGE(2)-levels in the cerebrospinal fluid. Neutralization of plasma PGE(2) with specific antibodies did not ameliorate the anorexia, and genetic deletion of microsomal PGE synthase-1 (mPGES-1) affected neither anorexia nor tumor growth. Furthermore, tumor-bearing mice lacking EP(4) receptors selectively in the nervous system developed anorexia. These observations suggest that COX-enzymes, most likely COX-1, are involved in cancer-elicited anorexia and weight loss, but that these phenomena occur independently of host mPGES-1, PGE(2) and neuronal EP(4) signaling.

  17. The effect of hydro-alcoholic extract of Artemisia absinthium on appetite in male rats

    Directory of Open Access Journals (Sweden)

    Sara Baghban Taraghdari

    2015-02-01

    Full Text Available Objectives: weight loss as a consecution of losing appetite in post-operative patients and those suffering from HIV, cancer, cachexia and inflammatory diseases are the main inducements of morbidity and mortality. There is an increasing demand for more efficacious and endurable appetite stimulating treatment for patients with cachexia. Health economics is influenced by the malnutrition which was accounted for 5% of Iranian populations in 2011. Artemisia absinthium is known as an orexigenic herb in Iranian traditional medicine. Little evidence is available about its orexigenic effect and mechanism. So, the present study evaluated the possible effect on appetite of hydroalcoholic extract of Artemisia absinthium. Materials and Methods: Thirty male Wistar rats were randomly divided into five groups. Vehicle group received 0.5 ml water per day, control group did not receive anything and other 3 groups received 50, 100 and 150 mg/kg of Artemisia absinthium for 7 days respectively. The daily amount of the food eaten by each rat was measured for 10 consecutive days. The amount of energy intake for each rat was also calculated for 7 days during the intervention. The difference in energy intake was calculated and compared between groups. Results: The results suggest that there was no significant (p>0.05 differences in energy received before and during intervention between three case groups compared with the control group. The energy intake in 1-2 hours after extract injection in all groups, and energy intake after 24 hours interval in third case group (receiving 150 mg/kg extract is higher compared to other intervals, but it is not significant (p>0.05. So, it can be stated that there was no significant differences between energy intake of 3 case groups and control group. Conclusion: Artemisia absinthium had no positive and dose-related effects on appetite of rats. Future studies are needed to evaluate the orexigenic effect of this plant.

  18. Subclinical myopathy in patients with colorectal cancer: clinical-pathological characterization and search for tissue markers

    Directory of Open Access Journals (Sweden)

    Massimo Vecchiato

    2012-03-01

    Full Text Available Skeletal muscle in patients with cancer undergoes many morphological changes due to immuno-inflammatory factors of tumor origin or treatment.T he latest event of these changes is cancer cachexia. Aim of the study is to identify myopathic features in skeletal muscle biopsies from weight stable patients with colorectal cancer and without cachexia or asthenia / weakness, that could possibly provide new diagnostic and prognostic cancer biomarkers. Morphometric analyses and immunohistochemical studies were performed on intraoperative muscle biopsies from patients with colorectal cancer and from weight stable patients undergoing surgery for benign non-inflammatory conditions. A rectus abdominis biopsy was taken in all patients and controls.A correlation between histopathologic findings and clinical characteristics, circulating inflammatory biomarkers and markers of muscle necrosis,surgery data and cancer phenotype were investigated.. Forty four patients (21male/23 female and 17 controls (6 male/11 female (p=NS were studied. In cancer patients’biopsies we observed asubclinical myopathy characterized by an abnormal distribution of myonuclei, which are localized inside the myofiber rather than at the periphery, and by the presence of regenerating muscle fibers. The percentage of myofibers with internalized nuclei is significantly higher in patients (median= 9%, IQR= 3.7-18.8 than in controls (median= 2.7%, IQR= 1.7-3.2 ( p=0.0002. In patients we observed an inverse correlation between the number of centronucleated fibers and the presence of node metastasis (N+(ρ=-0.64 (p=0.002. Patients affected with colorectal cancer display early sign of a myopathy, characterized by centronucleated and regenerating myofibers. This myopathy appears to be associated with an early stage of neoplasia and it could be an adaptive response of muscle to cancer. We hope a future application of these findings as a possible early diagnostic and prognostic biomarker of

  19. 中晚期肿瘤患者营养支持治疗的临床进展%Clinical progress of nutritional support therapy in patients with advanced cancer

    Institute of Scientific and Technical Information of China (English)

    林在楷; 殷保兵

    2015-01-01

    中晚期肿瘤患者在经历手术、化疗和放疗后,营养不良是导致其临床结局预后不佳的重要风险因素。恶病质可导致晚期肿瘤患者生存质量下降、死亡率升高、病死率增加以及治疗效果欠佳。通过提供营养支持,能避免肿瘤患者营养不良和体重减轻,满足患者的营养需求,并可预防、延缓肿瘤引起的恶病质的发生。该文综述肿瘤患者的营养与评估以及营养支持的应用进展。%Malnutrition is an important risk factor which results in poor clinical outcomes for patients with advanced cancer after they experience the surgical treatment and chemical/radiation therapy. The cachexia in advanced cancer patients leads to poor quality of life, high mortality and morbidity, and poor treatment responses. Nutrition support therapy in advanced cancer patients can not only provide nutritional support, reverse the nutritional deifcits and weight loss, but also prevent and delay the occurrence of cancer-related cachexia. This paper reviews the progress of nutrition and its evaluation, as well as nutritional support therapy in advanced cancer patients.

  20. Exploring metabolic dysfunction in chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Slee Adrian D

    2012-04-01

    Full Text Available Abstract Impaired kidney function and chronic kidney disease (CKD leading to kidney failure and end-stage renal disease (ESRD is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabolic factors may play key roles in CKD development and pathogenesis. These include raised proinflammatory cytokines, such as interleukin-1 and −6, tumor necrosis factor, altered hepatic acute phase proteins, including reduced albumin, increased C-reactive protein, and perturbations in normal anabolic hormone responses with reduced growth hormone-insulin-like growth factor-1 axis activity. Others include hyperactivation of the renin-angiotensin aldosterone system (RAAS, with angiotensin II and aldosterone implicated in hypertension and the promotion of insulin resistance, and subsequent pharmacological blockade shown to improve blood pressure, metabolic control and offer reno-protective effects. Abnormal adipocytokine levels including leptin and adiponectin may further promote the insulin resistant, and proinflammatory state in CKD. Ghrelin may be also implicated and controversial studies suggest activities may be reduced in human CKD, and may provide a rationale for administration of acyl-ghrelin. Poor vitamin D status has also been associated with patient outcome and CVD risk and may indicate a role for supplementation. Glucocorticoid activities traditionally known for their involvement in the pathogenesis of a number of disease states are increased and may be implicated in CKD-associated hypertension, insulin resistance, diabetes risk and cachexia, both directly and indirectly through effects on other systems including activation of the mineralcorticoid

  1. Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluoruracil in colon cancer cell-bearing mice

    Institute of Scientific and Technical Information of China (English)

    Simona Perboni; Cyril Bowers; Shinya Kojima; Akihiro Asakawa; Akio Inui

    2008-01-01

    The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemo-therapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin ago-nist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluoruracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BALB/c female tumour-bearing mice were randomized to receive a solution containing: (a) placebo; (b) GHRP-2; (c) 5-FU; or (d) 5-FU + GHRP-2. Ten BALB/c no tumour-bearing mice received placebo solution. Food intake and survival were checked. Six hours after the drug injection the cumulative food intake was significantly increased in mice treated with the combination of 5-FU + GHRP-2 versus the 5-FU alone (P = 0.0096). On day 3, the cumulative food intake of mice treated with GHRP-2, 5-FU and 5-FU + GHRP-2 significantly increased com-pared with naive and vehicle groups (P = 0.0007, P = 0.0038 and P = 0.0166, respectively). The median survival time was longer in 5-FU + GHRP-2 treated mice than in those with 5-FU, although it was not significant (18 d versus 15.5 d, P = 0.7). For the first time, we demonstrated that the addition of GHRP-2 to cytotoxic therapy with 5-FU improved appetite in tumour-bearing mice with anorexia/cachexia syndrome in early stage. These data suggest that GHRP-2 may improve the efficacy of therapy and the quality of life of cancer patients thank to the amelioration of their nutritional state.

  2. Thalidomide Celgene Corp.

    Science.gov (United States)

    Bruyn, G A

    1998-08-01

    Thalidomide, in development by Celgene, inhibits the effects of elevated TNFalpha and may consequently be of use in a range of diseases including cachexia, bacterial meningitis, rheumatoid arthritis, septic shock, AIDS, tuberculosis, multiple sclerosis, ulcerative colitis, graft-versus-host disease and systemic lupus erythematosus. In July 1998, Celgene received clearance from the US FDA to market and sell Thalomid (thalidomide) for the treatment of erythema nodosum leprosum (a severe and debilitating condition associated with leprosy) [291919], following a recommendation for approval by the FDA advisory committee in September 1997 [261846,263970]. In that same month, Celgene filed an IND for the treatment of the chronic autoimmune disorders Behcet's disease, and aphthosis [264366]. The trial will be conducted by investigators at the Mayo Clinic and Bowman Gray School of Medicine. It will be divided into two phases, the first phase lasting 4 weeks in which patients will receive 100 mg thalidomide or placebo, and a second open-label phase which will call back all patients to receive the same dose of thalidomide over a 24-week period. It will be determined whether the drug significantly reduces existing ulcerations and inhibits the formation of new lesions. Positive results of a National Institute of Allergy and Infectious Diseases trial for aphthous ulceration of the mouth in HIV-infected patients prompted Celgene to commence a pivotal trial for the same indication. A total of 84 patients will be randomized to 100 mg, 200 mg or 400 mg thalidomide/day for 4 weeks. Patients achieving a full response after 4 weeks will be re-randomized on 100 mg thalidomide or placebo for up to another year [248356]. The company has also completed the pivotal phase III trial for AIDS-related cachexia [225437]. Results from a pivotal phase II/III trial showed that the drug significantly increased body weight in AIDS patients, but also increased viral load initially. A total of 99

  3. C26 Cancer-Induced Muscle Wasting Is IKKβ-Dependent and NF-kappaB-Independent

    Science.gov (United States)

    Cornwell, Evangeline W.; Mirbod, Azadeh; Wu, Chia-Ling; Kandarian, Susan C.; Jackman, Robert W.

    2014-01-01

    Existing data suggest that NF-kappaB signaling is a key regulator of cancer-induced skeletal muscle wasting. However, identification of the components of this signaling pathway and of the NF-κB transcription factors that regulate wasting is far from complete. In muscles of C26 tumor bearing mice, overexpression of dominant negative (d.n.) IKKβ blocked muscle wasting by 69% and the IκBα-super repressor blocked wasting by 41%. In contrast, overexpression of d.n. IKKα or d.n. NIK did not block C26-induced wasting. Surprisingly, overexpression of d.n. p65 or d.n. c-Rel did not significantly affect muscle wasting. Genome-wide mRNA expression arrays showed upregulation of many genes previously implicated in muscle atrophy. To test if these upregulated genes were direct targets of NF-κB transcription factors, we compared genome-wide p65 binding to DNA in control and cachectic muscle using ChIP-sequencing. Bioinformatic analysis of ChIP-sequencing data from control and C26 muscles showed very little p65 binding to genes in cachexia and little to suggest that upregulated p65 binding influences the gene expression associated with muscle based cachexia. The p65 ChIP-seq data are consistent with our finding of no significant change in protein binding to an NF-κB oligonucleotide in a gel shift assay, no activation of a NF-κB-dependent reporter, and no effect of d.n.p65 overexpression in muscles of tumor bearing mice. Taken together, these data support the idea that although inhibition of IκBα, and particularly IKKβ, blocks cancer-induced wasting, the alternative NF-κB signaling pathway is not required. In addition, the downstream NF-κB transcription factors, p65 and c-Rel do not appear to regulate the transcriptional changes induced by the C26 tumor. These data are consistent with the growing body of literature showing that there are NF-κB-independent substrates of IKKβ and IκBα that regulate physiological processes. PMID:24489962

  4. ESPEN Guidelines on Parenteral Nutrition: non-surgical oncology.

    Science.gov (United States)

    Bozzetti, F; Arends, J; Lundholm, K; Micklewright, A; Zurcher, G; Muscaritoli, M

    2009-08-01

    Parenteral nutrition offers the possibility of increasing or ensuring nutrient intake in patients in whom normal food intake is inadequate and enteral nutrition is not feasible, is contraindicated or is not accepted by the patient. These guidelines are intended to provide evidence-based recommendations for the use of parenteral nutrition in cancer patients. They were developed by an interdisciplinary expert group in accordance with accepted standards, are based on the most relevant publications of the last 30 years and share many of the conclusions of the ESPEN guidelines on enteral nutrition in oncology. Under-nutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis and, per se, responsible for excess morbidity and mortality. Many indications for parenteral nutrition parallel those for enteral nutrition (weight loss or reduction in food intake for more than 7-10 days), but only those who, for whatever reason cannot be fed orally or enterally, are candidates to receive parenteral nutrition. A standard nutritional regimen may be recommended for short-term parenteral nutrition, while in cachectic patients receiving intravenous feeding for several weeks a high fat-to-glucose ratio may be advised because these patients maintain a high capacity to metabolize fats. The limited nutritional response to the parenteral nutrition reflects more the presence of metabolic derangements which are characteristic of the cachexia syndrome (or merely the short duration of the nutritional support) rather than the inadequacy of the nutritional regimen. Perioperative parenteral nutrition is only recommended in malnourished patients if enteral nutrition is not feasible. In non-surgical well-nourished oncologic patients routine parenteral nutrition is not recommended because it has proved to offer no advantage and is associated with increased morbidity. A benefit, however, is reported in patients undergoing hematopoietic stem cell transplantation

  5. Prognostic Impact of CT-Quantified Muscle and Fat Distribution before and after First-Line-Chemotherapy in Lung Cancer Patients

    Science.gov (United States)

    Nattenmüller, Johanna; Wochner, Raoul; Muley, Thomas; Steins, Martin; Hummler, Simone; Teucher, Birgit; Wiskemann, Joachim; Kauczor, Hans-Ulrich; Wielpütz, Mark Oliver; Heussel, Claus Peter

    2017-01-01

    Introduction Cachexia and sarcopenia are associated with poor outcome and increased chemotherapy-induced toxicity in lung cancer patients. However, the complex interplay of obesity, sarcopenia and cachexia, and its impact on survival in the context of first-line-chemotherapy is not yet understood. Methods In 200 consecutively recruited lung cancer patients (70 female, mean age 62y; mean BMI 25 kg/m2; median follow-up 15.97 months) with routine staging-CT before and after chemotherapy (CTX, mean interval: 4.3 months), densitometric quantification of total (TFA), visceral (VFA), and subcutaneous-fat-area (SFA), inter-muscular-fat-area (IMFA), muscle-density (MD), muscle-area (MA) and skeletal-muscle-index (SMI) was performed retrospectively to evaluate changes under chemotherapy and the impact on survival. Results We observed increases in TFA, VFA, SFA, VFA/SFA, and IMFA (p<0.05–0.001), while there were decreases in MA, MD and BMI (p<0.05–0.001) after chemotherapy. High pre-therapeutic VFA/SFA was a predictive factor for poor survival (HR = 1.272; p = 0.008), high pre-therapeutic MD for improved survival (HR = 0.93; p<0.05). Decrease in BMI (HR = 1.303; p<0.001), weight (HR = 1.067; p<0.001) and SMI (HR = 1.063; p<0.001) after chemotherapy were associated with poor survival. Patients with ≥4 CTX-cycles showed increased survival (17.6 vs. 9.1months), less muscle depletion (SMIdifference: p<0.05) and no BMI loss (BMIdifference: p<0.001). Conclusions After chemotherapy, patients exhibited sarcopenia with decreased muscle and increased adipose tissue compartments, which was not adequately mirrored by BMI and weight loss but by imaging. Particularly sarcopenic patients received less CTX-cycles and had poorer survival. As loss of BMI, weight and muscle were associated with poor survival, early detection (via imaging) and prevention (via physical exercise and nutrition) of sarcopenia may potentially improve outcome and reduce chemotherapy-induced toxicity. PMID

  6. Parenteral nutrition support for patients with pancreatic cancer. Results of a phase II study

    Directory of Open Access Journals (Sweden)

    Riess Hanno

    2010-03-01

    Full Text Available Abstract Background Cachexia is a common problem in patients (pts suffering from upper gastrointestinal cancer. In addition, most of these patients suffer from malabsorption and stenosis of the gastrointestinal tract due to their illness. Various methods of supplementary nutrition (enteral, parenteral are practised. In patients with advanced pancreatic cancer (APC, phase angle, determined by bio-electrical impedance analysis (BIA, seems to be a survival predictor. The positive influence of BIA determinate predictors by additional nutrition is currently under discussion. Methods To examine the impact of additional parenteral nutrition (APN we assessed outpatients suffering from APC and progressive cachexia. The assessment based on the BIA method. Assessment parameters were phase angle, ECM/BCM index (ratio of extracellular mass to body cell mass, and BMI (body mass index. Patients suffering from progressive weight loss in spite of additional enteral nutritional support were eligible for the study. Results Median treatment duration in 32 pts was 18 [8-35] weeks. Response evaluation showed a benefit in 27 pts (84% in at least one parameter. 14 pts (43.7% improved or stabilised in all three parameters. The median ECM/BCM index was 1.7 [1.11-3.14] at start of APN and improved down to 1.5 [1.12-3.36] during therapy. The median BMI increased from 19.7 [14.4-25.9] to 20.5 [15.4-25.0]. The median phase angle improved by 10% from 3.6 [2.3-5.1] to 3.9 [2.2-5.1]. Conclusions We demonstrated the positive impact of APN on the assessed parameters, first of all the phase angle, and we observed at least a temporary benefit or stabilisation of the nutritional status in the majority of the investigated patients. Based on these findings we are currently investigating the impact of APN on survival in a larger patient cohort. Trial registration ClinicalTrials.gov Identifier: NCT00919659

  7. C26 cancer-induced muscle wasting is IKKβ-dependent and NF-kappaB-independent.

    Directory of Open Access Journals (Sweden)

    Evangeline W Cornwell

    Full Text Available Existing data suggest that NF-kappaB signaling is a key regulator of cancer-induced skeletal muscle wasting. However, identification of the components of this signaling pathway and of the NF-κB transcription factors that regulate wasting is far from complete. In muscles of C26 tumor bearing mice, overexpression of dominant negative (d.n. IKKβ blocked muscle wasting by 69% and the IκBα-super repressor blocked wasting by 41%. In contrast, overexpression of d.n. IKKα or d.n. NIK did not block C26-induced wasting. Surprisingly, overexpression of d.n. p65 or d.n. c-Rel did not significantly affect muscle wasting. Genome-wide mRNA expression arrays showed upregulation of many genes previously implicated in muscle atrophy. To test if these upregulated genes were direct targets of NF-κB transcription factors, we compared genome-wide p65 binding to DNA in control and cachectic muscle using ChIP-sequencing. Bioinformatic analysis of ChIP-sequencing data from control and C26 muscles showed very little p65 binding to genes in cachexia and little to suggest that upregulated p65 binding influences the gene expression associated with muscle based cachexia. The p65 ChIP-seq data are consistent with our finding of no significant change in protein binding to an NF-κB oligonucleotide in a gel shift assay, no activation of a NF-κB-dependent reporter, and no effect of d.n.p65 overexpression in muscles of tumor bearing mice. Taken together, these data support the idea that although inhibition of IκBα, and particularly IKKβ, blocks cancer-induced wasting, the alternative NF-κB signaling pathway is not required. In addition, the downstream NF-κB transcription factors, p65 and c-Rel do not appear to regulate the transcriptional changes induced by the C26 tumor. These data are consistent with the growing body of literature showing that there are NF-κB-independent substrates of IKKβ and IκBα that regulate physiological processes.

  8. Comportamento do peso do coração e do corpo em chagásicos crônicos com e sem "megas"

    Directory of Open Access Journals (Sweden)

    Hipólito de Oliveira Almeida

    1980-12-01

    Full Text Available O peso do coração é menor nos chagásicos com "megas" do que nos falecidos subitamente ou em I.C.C., sendo, porém, maior que nos controles. Já o peso corporal ésemelhante nos chagásicos falecidos subitamente e nos controles, havendo redução moderada no grupo com I.C.C., e rtiais acentuada nos chagásicos com "megas" (redução de 20% em relação aos controles. A relação percentual peso cardíaco/peso corporal é de 1,1% no grupo com I.C.C.; 0,71% no grupo de morte súbita; 0,77% no grupo com "megas"; 0,49% no grupo controle e 0,60% ne grupo de doenças caquetizantes. Com base nas médias dos pesos cardíacos e corporal dos grupos controle, de doenças caquetizantes e de megas, calculou-se que o emagrecimento ocorrido nos megas reduziria o peso cardíaco médio de apenas 6,8%.Heart weight is less in chagasic patients with "mega" syndromes than in those which have died suddenly or with congestive heart failure, it is, however, greater than in the Controls. Body weight is similar in chagasic patients who have died suddenly and in the Controls, there is a moderate body weight reduction in the group with congestive heart failure, and a more accentuated reduction in chagasic patients with "mega" syndromes (a reduction of 20% in comparíson with the Controls. The relationship between heart - weight and body - weight, expressed as a percentage is 1,1% in the group with congestive heart failure; 0,71% in the group which died suddenly; 0.77% in the group with "mega" syndromes, 0.49% in the Controls group and 0.60% in the group with cachexia producing diseases. On the basis of mean heart - weights and body - weights of the control group, group with cachexia producing diseases and group with "mega" syndromes it was calculated that the emaciation which occurred in those with "mega"syndromes could reduce mean heart - weight by at least 6.8%.

  9. Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers

    Science.gov (United States)

    Skene, Debra J.; Middleton, Benita; Fraser, Cara K.; Pennings, Jeroen L. A.; Kuchel, Timothy R.; Rudiger, Skye R.; Bawden, C. Simon; Morton, A. Jennifer

    2017-01-01

    The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients. PMID:28223686

  10. Global Tumor RNA Expression in Early Establishment of Experimental Tumor Growth and Related Angiogenesis following Cox-Inhibition Evaluated by Microarray Analysis

    Directory of Open Access Journals (Sweden)

    Kent Lundholm

    2007-01-01

    Full Text Available Altered expression of COX-2 and overproduction of prostaglandins, particularly prostaglandin E2, are common in malignant tumors. Consequently, non-steroidal anti-inflammatory drugs (NSAIDs attenuate tumor net growth, tumor related cachexia, improve appetite and prolong survival. We have also reported that COX-inhibition (indomethacin interfered with early onset of tumor endothelial cell growth, tumor cell proliferation and apoptosis. It is however still unclear whether such effects are restricted to metabolic alterations closely related to eicosanoid pathways and corresponding regulators, or whether a whole variety of gene products are involved both up- and downstream effects of eicosanoids. Therefore, present experiments were performed by the use of an in vivo, intravital chamber technique, where micro-tumor growth and related angiogenesis were analyzed by microarray to evaluate for changes in global RNA expression caused by indomethacin treatment. Indomethacin up-regulated 351 and down-regulated 1852 genes significantly (p < 0.01; 1066 of these genes had unknown biological function. Genes with altered expression occurred on all chromosomes. Our results demonstrate that indomethacin altered expression of a large number of genes distributed among a variety of processes in the carcinogenic progression involving angiogenesis, apoptosis, cell-cycling, cell adhesion, inflammation as well as fatty acid metabolism and proteolysis. It remains a challenge to distinguish primary key alterations from secondary adaptive changes in transcription of genes altered by cyclooxygenase inhibition.

  11. Leishmaniasis in dogs: Case study

    Directory of Open Access Journals (Sweden)

    Aleksić Jelena

    2009-01-01

    Full Text Available The paper presents a case of leishmaniasis in a 2.5-month-old dog imported from France. The clinical examination established a generally poor state of health, expressed cachexia, atrophy of the temporal musculature, weakness of movement, as well as abnormally long and brittle nails. There was also hyperkeratosis of the nose tip and paws. A histological examination of biopsy sections of the altered skin parts showed inflammatory changes in the area of the dermis, together with infiltration of macrophages and a smaller number of lymphocytes, plasmocytes and neutrophil granulocytes in the area around the sebaceous glands and hair follicles. The determined changes correspond to superficial dermatitis. Edema followed by partial degeneration of connective-tissue fibers is observed in connective tissue. A smaller number of intracellular parasitic forms was established in mononuclear cells. A smaller number of oval amastigotes with round dark red nucleis were observed in sections stained using the Gimza method in the cytoplasm of macrophages located in the dermis, but also extracellularly. It was concluded that the dog was diseased with leishmaniasis on the grounds of the clinical picture and the microscopic findings.

  12. Growth hormone for optimization of refractory heart failure treatment

    Directory of Open Access Journals (Sweden)

    Bocchi Edimar Alcides

    1999-01-01

    Full Text Available It has been reported that growth hormone may benefit selected patients with congestive heart failure. A 63-year-old man with refractory congestive heart failure waiting for heart transplantation, depending on intravenous drugs (dobutamine and presenting with progressive worsening of the clinical status and cachexia, despite standard treatment, received growth hormone replacement (8 units per day for optimization of congestive heart failure management. Increase in both serum growth hormone levels (from 0.3 to 0.8 mg/l and serum IGF-1 levels (from 130 to 300ng/ml was noted, in association with clinical status improvement, better optimization of heart failure treatment and discontinuation of dobutamine infusion. Left ventricular ejection fraction (by MUGA increased from 13 % to 18 % and to 28 % later, in association with reduction of pulmonary pressures and increase in exercise capacity (rise in peak VO2 to 13.4 and to 16.2ml/kg/min later. The patient was "de-listed" for heart transplantation. Growth hormone may benefit selected patients with refractory heart failure.

  13. Comparison of Serum Lipid Levels in Chronic Obstructive Pulmonary Disease and Lung Cancer

    Directory of Open Access Journals (Sweden)

    Mehmet Kos

    2016-01-01

    Full Text Available Aim: Relationship between serum lipid level in chronic obstructive lung disease (COLD and lung cancer was not well documented. In our study we planned to compare serum lipid levels (Total Cholesterol-TC, low density lipoprotein cholesterol-LDL-C, trigliseride-TGL, and high density lipoprotein cholesterol-HDL-C in these common diseases. Material and Method: We evaluated 100 patients and 50 control group retrospectively. We enrolled the lipid parameters before any medical treatment start. Student%u2019s t-test and one-way ANOVA test was used for comparison of the patient characteristics and mean cholesterol level. Results: TC levels were higher in COLD disease than lung cancer group but not statistically significant. TGL levels were higher in lung cancer group than COLD and control group but this was also not statistically significant. Mild-moderate degree COLD patients had lower HDL-C than severe COLD patients (p=0.02. But TC and TGL levels were lower in severe COLD pateints. Small cell lung sancer and non-small lung cancers had statistically significantly lower TC and TGL levels (respectively p=0.04 and p=0.02. Discussion: We estimated that lipid leves of at the beginning of COLD were decreased to provide lipid necessity in cancer tissue due to tumor rapid cell proliferation in cancer, tumor cachexia and increased nutrition problems when developed lung cancer. Larger prospective studies are required to more accurate assessment this issue.

  14. Clinically relevant determinants of body composition, function and nutritional status as mortality predictors in lung cancer patients.

    Science.gov (United States)

    Kovarik, Miroslav; Hronek, Miloslav; Zadak, Zdenek

    2014-04-01

    Lung cancer belongs to the type of tumors with a relatively high frequency of malnutrition, sarcopenia and cachexia, severe metabolic syndromes related to impairment of physical function and quality of life, resistance to therapy and short survival. Inexpensive and accessible methods of evaluating changes in body composition, physical function and nutrition status are for this reason of great importance for clinical practice to enable the early identification, monitoring, preventing and treatment of these nutritional deficiencies. This could lead to improved outcomes in the quality of life, physical performance and survival of patients with lung cancer. The aim of this article is to summarize the recent knowledge for the use of such methods, their predictability for patient outcomes and an association with other clinically relevant parameters, specifically with lung cancer patients, because such an article collectively describing their practical application in clinical practice is lacking. The interest of this article is in the use of anthropometry, handgrip dynamometry, bioelectrical impedance analysis derived phase angle and nutritional screening questionnaires in lung cancer patients.

  15. The role of the endocannabinoid system in eating disorders: pharmacological implications.

    Science.gov (United States)

    Marco, Eva M; Romero-Zerbo, Silvana Y; Viveros, María-Paz; Bermudez-Silva, Francisco J

    2012-09-01

    The endocannabinoid (eCB) system is a widespread intercellular signalling mechanism that plays a critical role in body homoeostasis. It is located in key points involved in food intake and energy expenditure, coordinating all the players involved in energy balance. As such, it has come to be seen as an interesting target for the management of diseases characterized by an imbalanced energy homoeostasis, such as obesity and eating disorders. The aetiology of eating disorders and the molecular systems involved are still largely a mystery. Research has focused on brain circuits where the eCB system plays an important role, such as those related to feeding behaviour and the rewarding properties of food. Accordingly, recent findings have suggested a deregulation of the eCB system in eating disorders. At present, cannabinoid agonists are safe and effective tools in the management of diseases in which weight gain is needed, for example cachexia in AIDS patients. However, studies on the potential therapeutic validity of cannabinoids in eating disorders are scarce and inconclusive. Taken together, all these considerations warrant more preclinical and clinical investigations in the role of the eCB system in eating disorders. Eventually, they may provide novel pharmacological approaches for the treatment of these diseases.

  16. The brain endocannabinoid system in the regulation of energy balance.

    Science.gov (United States)

    Richard, Denis; Guesdon, Benjamin; Timofeeva, Elena

    2009-02-01

    The role played by the endocannabinoid system in the regulation of energy balance is currently generating a great amount of interest among several groups of investigators. This interest in large part comes from the urgent need to develop anti-obesity and anti-cachexia drugs around target systems (such as the endocannabinoid system), which appears to be genuinely involved in energy balance regulation. When activated, the endocannabinoid system favors energy deposition through increasing energy intake and reducing energy expenditure. This system is activated in obesity and following food deprivation, which further supports its authentic function in energy balance regulation. The cannabinoid receptor type 1 (CB1), one of the two identified cannabinoid receptors, is expressed in energy-balance brain structures that are also able to readily produce or inactivate N-arachidonoyl ethanolamine (anandamide) and 2-arachidonoylglycerol (2AG), the most abundantly formed and released endocannabinoids. The brain action of endocannabinoid system on energy balance seems crucial and needs to be delineated in the context of the homeostatic and hedonic controls of food intake and energy expenditure. These controls require the coordinated interaction of the hypothalamus, brainstem and limbic system and it appears imperative to unravel those interplays. It is also critical to investigate the metabolic endocannabinoid system while considering the panoply of functions that the endocannabinoid system fulfills in the brain and other tissues. This article aims at reviewing the potential mechanisms whereby the brain endocannabinoid system influences the regulation energy balance.

  17. A new surgical technique for perfusion of the epididymal fat pad in situ in rats.

    Science.gov (United States)

    Dauchy, Robert T; Blask, David E; Sauer, Leonard A

    2003-05-01

    We developed a new surgical technique for preparing the epididymal fat pad in rats for perfusion that maintains continuous blood flow. Epididymal fat pads can be perfused in situ using donor blood from either fed or fasted (24 h) animals. During the course of all perfusions, arterial and venous blood pH and gases were monitored and recorded. Total fatty acid (TFA) uptake and release by the epididymal fat depot was measured for the control and treatment perfusions; glycerol release was measured in all control perfusions. After addition of 14C-glucose to the donor-blood perfusate, all radioactivity appeared in the fat pad effluent blood; none appeared in the host systemic blood, and this finding indicated that the epididymal fat pad was separated from the host vasculature during perfusion in situ. The results presented here demonstrate excellent tissue function and metabolism, as a result of the perfusion technique. Our new surgical method for in vivo investigation of the epididymal fat pad, an important white adipose tissue, likely will have many applications in the study of lipid transport and metabolism, hyperlipidemia, obesity, and cancer cachexia.

  18. Aspectos clínicos e de laboratório de cães soropositivos para leishmaniose Clinical and laboratorial aspects of seropositive dogs to leishmaniosis

    Directory of Open Access Journals (Sweden)

    D.G. Mattos Jr.

    2004-02-01

    Full Text Available Leihsmaniasis is a protozoal disease transmitted by dipteran insects. The dog is an important domestic host of both visceral and cutaneous forms of the disease. These forms affects humans in many countries, and it is considered a serious risk for human health. This study reports clinical and laboratorial data from 18 dogs. Nine dogs were positive by indirect immunofluorescence technique and the other nine were negative. The dogs were clinically monitored for 30 days and laboratorial changes were assessed. Three blood samples were collected for hemogram and serum biochemistry at 0, 15, and 30 days. The clinical signs of positive dogs were compatible with the disease, including lymphadenopathy, cutaneous ulcers, hyperthermia, apathy, cachexia and ulcerated mucosa. Marked differences were observed in the blood cell counts and blood biochemistry between positive and negative dogs. In conclusion, blood and biochemistry analyses of positive dogs were not sufficient to diagnose the disease within the period studied. The serologic test associated with the clinical signs are important to confirm the diagnosis.

  19. Medium chain triglyceride (MCT) rich, paclitaxel loaded self nanoemulsifying preconcentrate (PSNP): a safe and efficacious alternative to Taxol.

    Science.gov (United States)

    Patel, Ketan; Patil, Anand; Mehta, Miten; Gota, Vikram; Vavia, Pradeep

    2013-12-01

    The current work was aimed to develop Medium Chain Triglyceride (MCT) rich self nanoemulsifying preconcentrate of paclitaxel (PTX) for parenteral delivery. Very high concentrations of Cremophor EL and ethanol in Taxol have rendered patients to severe side effects. Years of extensive research on development of cost effective and safer vehicle for PTX, have failed to provide a promising replacement for Taxol. MCT was selected as oil owing to its parenteral acceptability, high solubilization capacity and multiple therapeutic benefits in cancer cachexia. PTX precipitation kinetics and reported toxicity profile of Kolliphor HS15 has favored its selection for PTX Self Nanoemulsifying Preconcentrate (PSNP). Presence of 30% free PEG in Kolliphor HS15 (PEG-15-hydroxystearate) restricts its miscibility with MCT, imposing significant challenge in development of MCT rich self nanoemulsifying preconcentrate. Removal of PEG layer from oil-surfactant mixture facilitated the formulation of PSNP with 51% w/w MCT. PSNP exhibited better precipitation kinetic profile, higher PTX loading with negligible hemolysis and histamine release compared to Taxol. PSNP was bioequivalent to Taxol, though V(d) and MRT was significantly higher than Taxol. PSNP showed distinctly better profile in inhibiting tumor growth and maintaining body weight with significantly higher % survival. Thus, PSNP can be a safer vehicle with potential clinical benefits.

  20. A metabolic link to skeletal muscle wasting and regeneration

    Directory of Open Access Journals (Sweden)

    René eKoopman

    2014-02-01

    Full Text Available Due to its essential role in movement, insulating the internal organs, generating heat to maintain core body temperature, and acting as a major energy storage depot, any impairment to skeletal muscle structure and function may lead to an increase in both morbidity and mortality. In the context of skeletal muscle, altered metabolism is directly associated with numerous pathologies and disorders, including diabetes, and obesity, while many skeletal muscle pathologies have secondary changes in metabolism, including cancer cachexia, sarcopenia and the muscular dystrophies. Furthermore, the importance of cellular metabolism in the regulation of skeletal muscle stem cells is beginning to receive significant attention. Thus, it is clear that skeletal muscle metabolism is intricately linked to the regulation of skeletal muscle mass and regeneration. The aim of this review is to discuss some of the recent findings linking a change in metabolism to changes in skeletal muscle mass, as well as describing some of the recent studies in developmental, cancer and stem-cell biology that have identified a role for cellular metabolism in the regulation of stem cell function, a process termed ‘metabolic reprogramming’.