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Molecular mechanisms of cancer cachexia

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https://www.readbyqxmd.com/read/28529552/cancer-induced-muscle-wasting-latest-findings-in-prevention-and-treatment
#1
REVIEW
Zaira Aversa, Paola Costelli, Maurizio Muscaritoli
Cancer cachexia is a severe and disabling clinical condition that frequently accompanies the development of many types of cancer. Muscle wasting is the hallmark of cancer cachexia and is associated with serious clinical consequences such as physical impairment, poor quality of life, reduced tolerance to treatments and shorter survival. Cancer cachexia may evolve through different stages of clinical relevance, namely pre-cachexia, cachexia and refractory cachexia. Given its detrimental clinical consequences, it appears mandatory to prevent and/or delay the progression of cancer cachexia to its refractory stage by implementing the early recognition and treatment of the nutritional and metabolic alterations occurring during cancer...
May 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28296247/comprehensive-proteome-analysis-of-human-skeletal-muscle-in-cachexia-and-sarcopenia-a-pilot-study
#2
H Alexander Ebhardt, Simone Degen, Valentina Tadini, Alain Schilb, Neil Johns, Carolyn A Greig, Kenneth C H Fearon, Ruedi Aebersold, Carsten Jacobi
BACKGROUND: Cancer cachexia (cancer-induced muscle wasting) is found in a subgroup of cancer patients leaving the patients with a poor prognosis for survival due to a lower tolerance of the chemotherapeutic drug. The cause of the muscle wasting in these patients is not fully understood, and no predictive biomarker exists to identify these patients early on. Skeletal muscle loss is an inevitable consequence of advancing age. As cancer frequently occurs in old age, identifying and differentiating the molecular mechanisms mediating muscle wasting in cancer cachexia vs...
March 15, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28101649/molecular-mechanism-of-sarcopenia-and-cachexia-recent-research-advances
#3
REVIEW
Kunihiro Sakuma, Wataru Aoi, Akihiko Yamaguchi
Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Muscle loss occurs as a consequence of several chronic diseases (cachexia) and normal aging (sarcopenia). Although many negative regulators (atrogin-1, muscle ring finger-1, nuclear factor-kappaB (NF-κB), myostatin, etc.) have been proposed to enhance protein degradation during both sarcopenia and cachexia, the adaptation of these mediators markedly differs within both conditions. Sarcopenia and cachectic muscles have been demonstrated to be abundant in myostatin-linked molecules...
January 19, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27929469/the-colon-26-carcinoma-tumor-bearing-mouse-as-a-model-for-the-study-of-cancer-cachexia
#4
Andrea Bonetto, Joseph E Rupert, Rafael Barreto, Teresa A Zimmers
Cancer cachexia is the progressive loss of skeletal muscle mass and adipose tissue, negative nitrogen balance, anorexia, fatigue, inflammation, and activation of lipolysis and proteolysis systems. Cancer patients with cachexia benefit less from anti-neoplastic therapies and show increased mortality(1). Several animal models have been established in order to investigate the molecular causes responsible for body and muscle wasting as a result of tumor growth. Here, we describe methodologies pertaining to a well-characterized model of cancer cachexia: mice bearing the C26 carcinoma(2-4)...
November 30, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27919820/tnf-%C3%AE-and-cancer-cachexia-molecular-insights-and-clinical-implications
#5
REVIEW
Hetal J Patel, Bhoomika M Patel
Cancer cachexia characterized by a chronic wasting syndrome, involves skeletal muscle loss and adipose tissue loss and resistance to conventional nutritional support. Cachexia is responsible for the reduction in quality and length of life of cancer patients. It also decreases the muscle strength of the patients. The pro-inflammatory and pro-cachectic factors produced by the tumor cells have important role in genesis of cachexia. A number of pro-inflammatory cytokines, like interleukin-1 (IL-1), IL-6, tumor necrosis factor- alpha (TNF-α) may have important role in the pathological mechanisms of cachexia in cancer...
February 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/27916875/proteinase-activated-receptor-2-is-a-novel-regulator-of-tgf-%C3%AE-signaling-in-pancreatic-cancer
#6
REVIEW
David Witte, Franziska Zeeh, Thomas Gädeken, Frank Gieseler, Bernhard H Rauch, Utz Settmacher, Roland Kaufmann, Hendrik Lehnert, Hendrik Ungefroren
TGF-β has a dual role in tumorigenesis, acting as a tumor suppressor in normal cells and in the early stages of tumor development while promoting carcinogenesis and metastasis in advanced tumor stages. The final outcome of the TGF-β response is determined by cell-autonomous mechanisms and genetic alterations such as genomic instability and somatic mutations, but also by a plethora of external signals derived from the tumor microenvironment, such as cell-to-cell interactions, growth factors and extracellular matrix proteins and proteolytic enzymes...
November 30, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27748895/comparative-molecular-analysis-of-early-and-late-cancer-cachexia-induced-muscle-wasting-in-mouse-models
#7
COMPARATIVE STUDY
Rulin Sun, Santao Zhang, Xing Lu, Wenjun Hu, Ning Lou, Yan Zhao, Jia Zhou, Xiaoping Zhang, Hongmei Yang
Cancer-induced muscle wasting, which commonly occurs in cancer cachexia, is characterized by impaired quality of life and poor patient survival. To identify an appropriate treatment, research on the mechanism underlying muscle wasting is essential. Thus far, studies on muscle wasting using cancer cachectic models have generally focused on early cancer cachexia (ECC), before severe body weight loss occurs. In the present study, we established models of ECC and late cancer cachexia (LCC) and compared different stages of cancer cachexia using two cancer cachectic mouse models induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)...
December 2016: Oncology Reports
https://www.readbyqxmd.com/read/27667116/aliskiren-targets-multiple-systems-to-alleviate-cancer-cachexia
#8
Chaoyi Wang, Dunwei Guo, Qiang Wang, Song You, Zhongpeng Qiao, Yong Liu, Hang Dai, Hua Tang
To examine the effects of aliskiren, a small-molecule renin inhibitor, on cancer cachexia and to explore the underlying mechanisms. A cancer cachexia model was established by subcutaneously injecting C26 mouse colon carcinoma cells into isogenic BALB/c mice. Aliskiren was administered intragastrically [10 mg/kg body weight (BW)] on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection. Mice that received no C26 injection (healthy controls, HC group) or only C26 injection but not aliskiren (cancer, CA group) were used as controls...
November 2016: Oncology Reports
https://www.readbyqxmd.com/read/27531474/-cancer-cachexia-and-white-adipose-tissue-browning
#9
S T Zhang, H M Yang
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...
August 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/27443316/the-rationale-for-preventing-cancer-cachexia-targeting-excessive-fatty-acid-oxidation
#10
COMMENT
Chao-Nan Qian
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...
July 21, 2016: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/27388367/metformin-treatment-modulates-the-tumour-induced-wasting-effects-in-muscle-protein-metabolism-minimising-the-cachexia-in-tumour-bearing-rats
#11
André G Oliveira, Maria Cristina C Gomes-Marcondes
BACKGROUND: Cancer-cachexia state frequently induces both fat and protein wasting, leading to death. In this way, the knowledge of the mechanism of drugs and their side effects can be a new feature to treat and to have success, contributing to a better life quality for these patients. Metformin is an oral drug used in type 2 diabetes mellitus, showing inhibitory effect on proliferation in some neoplastic cells. For this reason, we evaluated its modulatory effect on Walker-256 tumour evolution and also on protein metabolism in gastrocnemius muscle and body composition...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27340276/molecular-pathways-cachexia-signaling-a-targeted-approach-to-cancer-treatment
#12
Yuji Miyamoto, Diana L Hanna, Wu Zhang, Hideo Baba, Heinz-Josef Lenz
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...
August 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27317993/animal-models-of-cardiac-cachexia
#13
REVIEW
Francesca Molinari, Natalia Malara, Vincenzo Mollace, Giuseppe Rosano, Elisabetta Ferraro
Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms...
September 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27249757/treatment-of-lung-cancer-in-medically-compromised-patients
#14
Jeffrey Crawford, Paul Wheatley-Price, Josephine Louella Feliciano
Outcomes for patients with lung cancer have been improved substantially through the integration of surgery, radiation, and systemic therapy for patients with early-stage disease. Meanwhile, advances in our understanding of molecular mechanisms have substantially advanced our treatment of patients with advanced lung cancer through the introduction of targeted therapies, immune approaches, improvements in chemotherapy, and better supportive care. However, the majority of these advances have occurred among patients with good functional status, normal organ function, and with the social and economic support systems to be able to benefit most from these treatments...
2016: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/27239403/map3k11-gdf15-axis-is-a-critical-driver-of-cancer-cachexia
#15
Lorena Lerner, Julie Tao, Qing Liu, Richard Nicoletti, Bin Feng, Brian Krieger, Elizabeth Mazsa, Zakir Siddiquee, Ruoji Wang, Lucia Huang, Luhua Shen, Jie Lin, Antonio Vigano, M Isabel Chiu, Zhigang Weng, William Winston, Solly Weiler, Jeno Gyuris
BACKGROUND: Cancer associated cachexia affects the majority of cancer patients during the course of the disease and thought to be directly responsible for about a quarter of all cancer deaths. Current evidence suggests that a pro-inflammatory state may be associated with this syndrome although the molecular mechanisms responsible for the development of cachexia are poorly understood. The purpose of this work was the identification of key drivers of cancer cachexia that could provide a potential point of intervention for the treatment and/or prevention of this syndrome...
September 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27228549/long-term-exercise-training-prevents-mammary-tumorigenesis-induced-muscle-wasting-in-rats-through-the-regulation-of-tweak-signalling
#16
A I Padrão, A C C Figueira, A I Faustino-Rocha, A Gama, M M Loureiro, M J Neuparth, D Moreira-Gonçalves, R Vitorino, F Amado, L L Santos, P A Oliveira, J A Duarte, R Ferreira
AIM: Exercise training has been suggested as a non-pharmacological approach to prevent skeletal muscle wasting and improve muscle function in cancer cachexia. However, little is known about the molecular mechanisms underlying such beneficial effect. In this study, we aimed to, firstly, examine the contribution of TWEAK signalling to cancer-induced skeletal muscle wasting and, secondly, evaluate whether long-term exercise alters TWEAK signalling and prevents muscle wasting. METHODS: Female Sprague-Dawley rats were randomly assigned to control and exercise groups...
May 26, 2016: Acta Physiologica
https://www.readbyqxmd.com/read/27178882/molecular-mechanisms-of-cancer-cachexia
#17
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
June 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27108265/pay-attention-to-cardiac-remodeling-in-cancer-cachexia
#18
REVIEW
Yawen Zheng, Han Chen, Xiaoqing Li, Yuping Sun
Cancer cachexia is a complex and multifaceted disease state characterized by fatigue, weakness, and loss of skeletal muscle and adipose tissue. Recently, the profound negative effects of cancer cachexia on cardiac tissue draw much attention, which is likely to contribute to mortality in tumor-bearing animals. The mechanism of cardiac remodeling is not so clear and involved with a series of molecular alterations. In cancer cachexia model, progressive loss of left ventricular mass and decrease in myocardial function is observed and cardiac autonomic functions are altered...
July 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/27034684/spontaneous-physical-activity-downregulates-pax7-in-cancer-cachexia
#19
Dario Coletti, Paola Aulino, Eva Pigna, Fabio Barteri, Viviana Moresi, Daniela Annibali, Sergio Adamo, Emanuele Berardi
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...
2016: Stem Cells International
https://www.readbyqxmd.com/read/26673867/activin-%C3%AE-c-modulates-cachexia-by-repressing-the-ubiquitin-proteasome-and-autophagic-degradation-pathways
#20
Francesco Elia Marino, Gail Risbridger, Elspeth Gold
BACKGROUND: Cancer-associated cachexia and muscle wasting are considered key determinants of cancer-related death and reduction in the quality of life of cancer patients. A crucial link has been established between activin signaling and skeletal muscle atrophy-hypertrophy. We previously showed that activin-βC, a novel activin-A antagonist, is a tumor modulator that abolishes the cancer-associated cachexia in a mouse genetic model of gonadal tumorigenesis, in which the normal balance of inhibin/activin signalling is disrupted by a targeted mutation in the Inha gene (inhibin α-KO mouse)...
December 2015: Journal of Cachexia, Sarcopenia and Muscle
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