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Molecular mechanisms of cancer cachexia

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https://www.readbyqxmd.com/read/27919820/tnf-%C3%AE-and-cancer-cachexia-molecular-insights-and-clinical-implications
#1
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...
December 2, 2016: Life Sciences
https://www.readbyqxmd.com/read/27916875/proteinase-activated-receptor-2-is-a-novel-regulator-of-tgf-%C3%AE-signaling-in-pancreatic-cancer
#2
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
#3
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)...
October 12, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27667116/aliskiren-targets-multiple-systems-to-alleviate-cancer-cachexia
#4
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...
September 21, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27531474/-cancer-cachexia-and-white-adipose-tissue-browning
#5
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
#6
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...
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
Ana Isabel Padrão, Ana Cristina Corrêa Figueira, Ana Rocha-Faustino, Adelina Gama, Maria Margarida Loureiro, Maria João Neuparth, Daniel Moreira-Gonçalves, Rui Vitorino, Francisco Amado, Lúcio Lara Santos, Paula A Oliveira, José Alberto Duarte, Rita 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 the present 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
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/26506009/muscle-bone-interactions-from-experimental-models-to-the-clinic-a-critical-update
#17
Michaël R Laurent, Vanessa Dubois, Frank Claessens, Sabine M P Verschueren, Dirk Vanderschueren, Evelien Gielen, Ferran Jardí
Bone is a biomechanical tissue shaped by forces from muscles and gravitation. Simultaneous bone and muscle decay and dysfunction (osteosarcopenia or sarco-osteoporosis) is seen in ageing, numerous clinical situations including after stroke or paralysis, in neuromuscular dystrophies, glucocorticoid excess, or in association with vitamin D, growth hormone/insulin like growth factor or sex steroid deficiency, as well as in spaceflight. Physical exercise may be beneficial in these situations, but further work is still needed to translate acceptable and effective biomechanical interventions like vibration therapy from animal models to humans...
September 5, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/26227583/omega-3-polyunsaturated-fatty-acids-and-cancer-lessons-learned-from-clinical-trials
#18
REVIEW
Seyed Fazel Nabavi, Stefania Bilotto, Gian Luigi Russo, Ilkay Erdogan Orhan, Solomon Habtemariam, Maria Daglia, Kasi Pandima Devi, Monica Rosa Loizzo, Rosa Tundis, Seyed Mohammad Nabavi
Over the past decades, extensive studies have addressed the therapeutic effects of omega-3 polyunsaturated fatty acids (omega-3 FAs) against different human diseases such as cardiovascular and neurodegenerative diseases, cancer, etc. A growing body of scientific research shows the pharmacokinetic information and safety of these natural occurring substances. Moreover, during recent years, a plethora of studies has demonstrated that omega-3 FAs possess therapeutic role against certain types of cancer. It is also known that omega-3 FAs can improve efficacy and tolerability of chemotherapy...
September 2015: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/26136189/ghrelin-prevents-tumour-and-cisplatin-induced-muscle-wasting-characterization-of-multiple-mechanisms-involved
#19
Ji-An Chen, Andres Splenser, Bobby Guillory, Jiaohua Luo, Meenal Mendiratta, Blaga Belinova, Tripti Halder, Guohua Zhang, Yi-Ping Li, Jose M Garcia
BACKGROUND: Cachexia and muscle atrophy are common consequences of cancer and chemotherapy administration. The novel hormone ghrelin has been proposed as a treatment for this condition. Increases in food intake and direct effects on muscle proteolysis and protein synthesis are likely to mediate these effects, but the pathways leading to these events are not well understood. METHODS: We characterized molecular pathways involved in muscle atrophy induced by Lewis lung carcinoma (LLC) tumour implantation in c57/bl6 adult male mice and by administration of the chemotherapeutic agent cisplatin in mice and in C2C12 myotubes...
June 2015: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/26112046/molecular-and-neuroendocrine-mechanisms-of-cancer-cachexia
#20
REVIEW
Maria Carolina S Mendes, Gustavo D Pimentel, Felipe O Costa, José B C Carvalheira
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...
September 2015: Journal of Endocrinology
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