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Proinflammatory cytokines in cancer cachexia

Gökcen Demiray, Serkan Değirmencioğlu, Erhan Uğurlu, Arzu Yaren
INTRODUCTION: Cancer cachexia is one of the most frequent effects of malignancy, is often associated with poor prognosis, and may account for up to 20% of cancer deaths. The aim of our study was to evaluate the relationship of cancer cachexia and serum levels of resistin and leptin in patients with advanced non-small cell lung cancer. METHODS: A total of 67 chemotherapy-naïve patients with advanced-stage non-small cell cancer and a control group containing 20 healthy individuals without a known chronic disease were enrolled in this study...
2017: Clinical Medicine Insights. Oncology
Alexandre Abilio de Souza Teixeira, Fábio Santos Lira, Gustavo D Pimentel, Camila Oliveira de Souza, Helena Batatinha, Luana A Biondo, Alex S Yamashita, Edson A Lima Junior, José Cesar Rosa Neto
White adipose tissue (WAT) is no longer considered a tissue whose main function is the storage of TAG. Since the discovery of leptin in 1994, several studies have elucidated the important role of WAT as an endocrine organ, the source of the adipokines. The low-grade inflammation observed in obese and cancer cachexia patients is explained, at least partially, by the exacerbated release of proinflammatory adipokines. Despite of the recent progress in the characterization of the various adipokines and lipokines produced by WAT, little is known about the mechanisms regulating the secretion of these molecules in different physiological and pathological circumstances...
2016: Critical Reviews in Eukaryotic Gene Expression
Yang Quan-Jun, Huo Yan, Han Yong-Long, Wan Li-Li, Li Jie, Huang Jin-Lu, Lu Jin, Chen Peng-Guo, Gan Run, Guo Cheng
Cancer cachexia is a multifactorial syndrome affecting the skeletal muscle. Previous clinical trials showed that treatment with MEK inhibitor selumetinib resulted in skeletal muscle anabolism. However, it is conflicting that MAPK/ERK pathway controls the mass of the skeletal muscle. The current study investigated the therapeutic effect and mechanisms of selumetinib in amelioration of cancer cachexia. The classical cancer cachexia model was established via transplantation of CT26 colon adenocarcinoma cells into BALB/c mice...
February 2017: Molecular Cancer Therapeutics
Hikaru Sato, Takafumi Naito, Takuya Ishida, Junichi Kawakami
PURPOSE: Elevated serum proinflammatory cytokines are associated with the reduction of cytochrome P450 enzyme (CYP) activity. This study aimed to evaluate the oxycodone pharmacokinetics, central symptoms, and serum proinflammatory cytokines based on cachexia stage in cancer patients. METHODS: Forty-seven cancer patients receiving extended-release oxycodone were enrolled. Predose plasma concentrations of oxycodone and its metabolites were normalized with the daily dose and body weight...
December 2016: European Journal of Clinical Pharmacology
F Marchildon, D Fu, N Lala-Tabbert, N Wiper-Bergeron
CCAAT/enhancer binding protein beta (C/EBPβ), a transcription factor expressed in muscle satellite cells (SCs), inhibits the myogenic program and is downregulated early in differentiation. In a conditional null model in which C/EBPβ expression is knocked down in paired box protein 7+ (Pax7+) SCs, cardiotoxin (CTX) injury is poorly repaired, although muscle regeneration is efficient in control littermates. While myoblasts lacking C/EBPβ can differentiate efficiently in culture, after CTX injury poor regeneration was attributed to a smaller than normal Pax7+ population, which was not due to a failure of SCs to proliferate...
February 25, 2016: Cell Death & Disease
Meng-Chuan Chen, Yen-Lin Chen, Chi-Feng Lee, Chih-Huang Hung, Tz-Chong Chou
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)...
2015: PloS One
Nelson Inácio Pinto, June Carnier, Lila M Oyama, Jose Pinhata Otoch, Paulo Sergio Alcântara, Flavio Tokeshi, Claudia M Nascimento
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...
2015: Mediators of Inflammation
Alessio Molfino, Gianfranco Gioia, Filippo Rossi Fanelli, Alessandro Laviano
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...
2015: Mediators of Inflammation
Michal Rihacek, Julie Bienertova-Vasku, Dalibor Valik, Jaroslav Sterba, Katerina Pilatova, Lenka Zdrazilova-Dubska
B-cell activating factor (BAFF) is a cytokine and adipokine of the TNF ligand superfamily. The main biological function of BAFF in maintaining the maturation of B-cells to plasma cells has recently made it a target of the first FDA-approved selective BAFF antibody, belimumab, for the therapy of systemic lupus erythematosus. Concomitantly, the role of BAFF in cancer has been a subject of research since its discovery. Here we review BAFF as a biomarker of malignant disease activity and prognostic factor in B-cell derived malignancies such as multiple myeloma...
2015: BioMed Research International
Giulia Pappalardo, Ana Almeida, Paula Ravasco
OBJECTIVES: The objective of this review article is to present the most recent intervention studies with EPA on nutritional outcomes in cancer patients, e.g. nutritional status, weight & lean body mass. METHODS: For this purpose a PubMed(®) and MedLine(®) search of the published literature up to and including January 2014 that contained the keywords: cancer, sarcopenia, EPA, ω-3 fatty acids, weight, intervention trial, muscle mass was conducted. The collected data was summarized and written in text format and in tables that contained: study design, patient' population, sample size, statistical significance and results of the intervention...
April 2015: Nutrition
Youn Kyung Choi, Ki Yong Jung, Sang-Mi Woo, Yee Jin Yun, Chan-Yong Jun, Jong Hyeong Park, Yong Cheol Shin, Sung-Gook Cho, Seong-Gyu Ko
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...
2014: Mediators of Inflammation
Takashi Yazawa, Masahiko Shibata, Kenji Gonda, Takeshi Machida, Satoshi Suzuki, Akira Kenjo, Izumi Nakamura, Takao Tsuchiya, Yoshihisa Koyama, Kenichi Sakurai, Tatsuo Shimura, Ryouichi Tomita, Hitoshi Ohto, Mitsukazu Gotoh, Seiichi Takenoshita
Although a causal relationship between inflammation and innate immunity of cancer is more widely accepted today, many of the precise cell mechanisms mediating this relationship have not been elucidated. Th17 cells, which produce the proinflammatory cytokine interleukin 17 (IL-17), have been recognized as one of the key factors in the regulation of inflammatory bowel disease and rheumatoid arthritis. This study demonstrated that, in patients with various types of gastrointestinal cancer, IL-17 production was correlated with myeloid-derived suppressor cell (MDSC) levels and with markers for nutritional impairment, immune suppression and chronic inflammation...
July 2013: Molecular and Clinical Oncology
Kamil Grabiec, Marta Burchert, Marta Milewska, Maciej Błaszczyk, Katarzyna Grzelkowska-Kowalczyk
Cachexia is a multifactorial syndrome of atrophy of skeletal muscle and adipose tissue, resulting in progressive loss of body weight associated with low quality of life and poor prognosis in cancer. Studies on experimental animal models and observations on patients have shown that the soluble factors secreted by tumor cells and tissues of the patient can participate in regulation of the wasting process. Cachexia is often accompanied by anorexia, which is caused by predominance of signals inhibiting appetite in the hypothalamus, such as release of proopiomelanocortin and anorexigenic action of proinflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α)...
December 31, 2013: Postȩpy Higieny i Medycyny Doświadczalnej
Andrea Nicolini, Paola Ferrari, Maria Chiara Masoni, Milena Fini, Stefania Pagani, Ottavio Giampietro, Angelo Carpi
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)...
October 2013: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Quanjun Yang, Lili Wan, Zhiyong Zhou, Yan Li, Qi Yu, Liya Liu, Bin Li, Cheng Guo
Excessive elaboration of proinflammatory cytokines are involved in cachexia-related hypercatabolism. Parthenolide, as a potential anti-inflammatory active agent, could effectively inhibit nuclear factor-kappa B, and has the potential for the treatment of cancer cachexia. In this study, the cancer cachexia model was established by subcutaneous transplantation CT26 tumor fragment. Parthenolide or placebo was intraperitoneally given daily from the next day. Parthenolide treatment could effectively preserve the body weight, improve the mass of gastrocnemius and tibialis anterior muscles, and alleviate tumor burden...
August 15, 2013: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Jeremy Steinman, Mark Daniel DeBoer
Cachexia is a condition typified by wasting of fat and LBM caused by anorexia and further endocrinological modulation of energy stores. Diseases known to cause cachectic symptoms include cancer, chronic kidney disease, and chronic heart failure; these conditions are associated with increased levels of proinflammatory cytokines and increased resting energy expenditure. Early studies have suggested the central melanocortin system as one of the main mediators of the symptoms of cachexia. Pharmacological and genetic antagonism of these pathways attenuates cachectic symptoms in laboratory models; effects have yet to be studied in humans...
2013: Vitamins and Hormones
Liuping Zhang, Hua Tang, Yao Kou, Rui Li, Yueyong Zheng, Qiang Wang, Xiaoyu Zhou, Liangbin Jin
PURPOSE: To evaluate the effect of proteasome inhibitor MG132 in cancer cachexia and to delineate the molecular mechanism underlying. METHODS: We established an experimental cancer cachexia model by subcutaneously implanting colon 26 cells into the armpits of BALB/c mice. Following administration of MG132 at various time points, body weight, food intake, gastrocnemius muscle weight, spontaneous activity and survival of tumor-bearing mice were examined along with tumor growth...
July 2013: Journal of Cancer Research and Clinical Oncology
Christina Wu, Soledad A Fernandez, Tamara Criswell, Tarek A Chidiac, Denis Guttridge, Miguel Villalona-Calero, Tanios S Bekaii-Saab
OBJECTIVES: Etanercept blocks tumor necrosis factor α (TNF-α), a proinflammatory cytokine that plays a role in cancer-related cachexia and tumor growth. A phase I/II study was conducted to assess the tolerability and efficacy of gemcitabine and etanercept in advanced pancreatic cancer. METHODS: Twenty-five patients received etanercept 25 mg subcutaneously twice weekly with gemcitabine. A control cohort of 8 patients received gemcitabine alone. The primary end point was progression-free survival at 6 months...
July 2013: Pancreas
Suzu Yae, Fumiyuki Takahashi, Toshifumi Yae, Takuji Yamaguchi, Rika Tsukada, Kengo Koike, Kunihiko Minakata, Akiko Murakami, Fariz Nurwidya, Motoyasu Kato, Mayumi Tamada, Momoko Yoshikawa, Hiroyuki Kobayashi, Kuniaki Seyama, Kazuhisa Takahashi
Cachexia, a major cause of cancer-related death, is characterized by depletion of muscle and fat tissues, anorexia, asthenia, and hypoglycemia. Recent studies indicate that secretions of proinflammatory cytokines such as interleukin-6 (IL-6) play a crucial role in cachexia development, and that these cytokines are secreted from not only cancer cells but also host cells such as macrophages. In this study, we investigated the therapeutic effects of hochuekkito, a Kampo formula, on cachexia induced by colon 26 adenocarcinoma in mice...
2012: Evidence-based Complementary and Alternative Medicine: ECAM
Simone Lucia, Martina Esposito, Filippo Rossi Fanelli, Maurizio Muscaritoli
Cancer cachexia is a disabling syndrome because of the complex interactions between the tumor, host metabolism, and proinflammatory cytokines that increases patients' morbidity and mortality. Considering the recent new definition and classification of cachexia, we aimed to review cancer cachexia from its underlying mechanisms to the clinical approach. Cancer cachexia is featured by a disruption in energy balance, metabolic changes, a decrease in fat mass, depletion of skeletal muscle mass, and perturbations in proinflammatory cytokines...
2012: Critical Reviews in Oncogenesis
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