scholarly journals An integrative transcriptome study reveals Ddit4/Redd1 as a key regulator of cancer cachexia in rodent models

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Mengyuan Niu ◽  
Li Li ◽  
Zhonglan Su ◽  
Lulu Wei ◽  
Wenyuan Pu ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Xenograft Model ◽  
Interaction Network ◽  
Bioinformatic Analysis ◽  
Pathological Process ◽  
Protein Protein Interaction ◽  
Kegg Pathways

AbstractCancer cachexia is a multifactorial metabolic syndrome that causes up to 20% of cancer-related deaths. Muscle atrophy, the hallmark of cancer cachexia, strongly impairs the quality of life of cancer patients; however, the underlying pathological process is still poorly understood. Investigation of the disease pathogenesis largely relies on cachectic mouse models. In our study, the transcriptome of the cachectic gastrocnemius muscle in the C26 xenograft model was integrated and compared with that of 5 more different datasets. The bioinformatic analysis revealed pivotal gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the disease, and the key genes were validated. Construction of the protein-protein interaction network and the comparison of pathways enriched in cancer cachexia with 5 other muscle atrophy models revealed Ddit4 (DNA damage-inducible transcript 4), as a key protein in cancer cachexia. The higher expression of Ddit4 in cachectic muscle was further validated in animal models and cachectic cancer patients. Further study revealed that p38 induced the expression of Ddit4, which in turn inhibited the mTOR pathway in atrophic cells.

scholarly journals Bioinformatic Analysis of Neuroimmune Mechanism of Neuropathic Pain

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hao Yu ◽  
Yang Liu ◽  
Chao Li ◽  
Jianhao Wang ◽  
Bo Yu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Responses ◽  
Interaction Network ◽  
Gene Interaction ◽  
Bioinformatic Analysis ◽  
Venn Diagram ◽  
Hub Genes ◽  
Gene Interaction Network ◽  
Pathway Enrichment ◽  
Protein Protein Interaction

Background. Neuropathic pain (NP) is a devastating complication following nerve injury, and it can be alleviated by regulating neuroimmune direction. We aimed to explore the neuroimmune mechanism and identify some new diagnostic or therapeutic targets for NP treatment via bioinformatic analysis. Methods. The microarray GSE18803 was downloaded and analyzed using R. The Venn diagram was drawn to find neuroimmune-related differentially expressed genes (DEGs) in neuropathic pain. Gene Ontology (GO), pathway enrichment, and protein-protein interaction (PPI) network were used to analyze DEGs, respectively. Besides, the identified hub genes were submitted to the DGIdb database to find relevant therapeutic drugs. Results. A total of 91 neuroimmune-related DEGs were identified. The results of GO and pathway enrichment analyses were closely related to immune and inflammatory responses. PPI analysis showed two important modules and 8 hub genes: PTPRC, CD68, CTSS, RAC2, LAPTM5, FCGR3A, CD53, and HCK. The drug-hub gene interaction network was constructed by Cytoscape, and it included 24 candidate drugs and 3 hub genes. Conclusion. The present study helps us better understand the neuroimmune mechanism of neuropathic pain and provides some novel insights on NP treatment, such as modulation of microglia polarization and targeting bone resorption. Besides, CD68, CTSS, LAPTM5, FCGR3A, and CD53 may be used as early diagnostic biomarkers and the gene HCK can be a therapeutic target.

Weight and Appetite Loss in Cancer

2021 ◽  
pp. 298-302
Author(s):  
Yesne Alici ◽  
Victoria Saltz
Keyword(s):  
Cancer Patients ◽  
Cancer Cachexia ◽  
Sense Of Self ◽  
Resting Energy Expenditure ◽  
Appetite Loss ◽  
Chronic Inflammatory Response ◽  
Variable Combination ◽  
Cancer Anorexia ◽  
Cachexia Syndrome

Weight and appetite loss in cancer patients, referred to as the cancer anorexia-cachexia syndrome, is a complex, multifactorial syndrome, defined by an ongoing loss of skeletal muscle mass, with or without loss of fat mass, which cannot be fully reversed by conventional nutritional support, and may lead to progressive functional impairment. It is a hypercatabolic state in the context of chronic inflammatory response best described in the setting of cancer but can also be seen in other advanced chronic illness. Cancer cachexia occurs in approximately 50% of cancer patients, and in 80% of those with advanced cancer. It impacts adversely on function, treatment tolerability and treatment response, and health service utilization, but most importantly, dignity, sense of self, quality of life, and survival. The pathophysiology of cancer cachexia is complex and multifactorial. It is characterized by a negative protein and energy balance, driven by a variable combination of reduced food intake, increased resting energy expenditure, and net loss of lean tissue. The best approach to weight and appetite loss among cancer patients is a multimodal therapy, in which a personalized combination of pharmacologic and nonpharmacologic treatments is implemented. This chapter will provide an overview of the cancer anorexia cachexia syndrome as relevant to the practice of clinicians of all disciplines managing cancer patients.

scholarly journals Exercise as a Time-conditioning Effector in Chronic Disease: a Complementary Treatment Strategy

2004 ◽  
Vol 1 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Luis F. B. P. Costa Rosa
Keyword(s):  
Cancer Patients ◽  
Cancer Cachexia ◽  
Fat Body ◽  
Exercise Program ◽  
The Body ◽  
Progressive Weight Loss ◽  
Important Time ◽  
Complementary Strategy ◽  
Fat Body Mass

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.

scholarly journals Medical Cannabinoids for Cancer Cachexia: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Jing Wang ◽  
Yanling Wang ◽  
Mengting Tong ◽  
Hongming Pan ◽  
Da Li
Keyword(s):  
Quality Of Life ◽  
Cancer Patients ◽  
Cancer Cachexia ◽  
Meta Analysis ◽  
Life Quality ◽  
Cochrane Library ◽  
Cochrane Central Register ◽  
Negative Effects ◽  
Central Register

Objectives. Cancer cachexia (CCA) is an intractable and ineffective metabolic syndrome that attacks 50–80% of cancer patients. It reduces patient’s life quality, affects the efficacy of treatment, and then increases their mortality; however, there are no established therapeutic strategies for CCA in the world. In this study, we assess the positive and negative effects of cannabinoid in the treatment of CCA. Methods. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Web of Science, and PubMed up to December 2017. Results. Of the 256 screened studies, three studies with a total of 592 participants were included. Compared with placebo, cannabinoid increased the appetite (MD 0.27, 95% CI -0.51 to 1.04; n= 3) but failed to improve the overall quality of life (QOL; MD -12.39, 95% CI [-24.21 to -0.57; n = 2), and a total of 441 patients had 607 adverse events (AEs; 496 in the cannabinoid group and 111 in the placebo group). Conclusions. Our analysis showed cannabinoid is effective in increasing appetite in cancer patients. However, it declines the quality of life, which may be due to the side effects of cannabinoid.

Leucine-rich Diet Improved Muscle Function in Cachectic Walker 256 Tumor-bearing Wistar Rats

2021 ◽  
Author(s):  
Laís Viana ◽  
Gabriela Chiocchetti ◽  
Lucas Oroy ◽  
Willians Vieira ◽  
Carla Salgado ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Muscle Atrophy ◽  
Muscle Function ◽  
Cancer Cachexia ◽  
Muscle Protein ◽  
Tumor Bearing ◽  
Muscle Protein Degradation ◽  
Walker 256 ◽  
Walker 256 Tumor

Abstract Background: Skeletal muscle atrophy occurs in several pathological conditions such as cancer, a condition termed cancer cachexia. This condition is associated with an increase in morbidity and poor treatment response, decreasing quality of life, and increased mortality in cancer patients. A leucine-rich diet could be used as a coadjutant therapy preventing muscle atrophy in cancer cachexia hosts. Besides muscle atrophy, muscle function loss is even more important to the patient’s quality of life. Therefore, this study aimed to evaluate the effects of leucine-rich diet on muscle function activity of cachectic Walker 256 tumor-bearing rats and to correlate such effects with molecular pathways of muscle atrophy. Methods: Adult Wistar rats were randomly distributed into four experimental groups. Two groups were fed with a control diet: Control (C) and Walker 256 tumor-bearing (W), and two other groups were fed with a leucine-rich diet: Leucine Control (L) and Leucine Walker 256 tumor-bearing (LW). The functional analysis (walking, behavior, and strength tests) was measured and before and after tumor inoculation. Cachexia parameters such as body weight loss, muscle and fat mass, pro-inflammatory cytokine profile, and molecular and morphological aspects of skeletal muscle were also performed. Results: Walker 256 tumor growth led to muscle function decline, cachexia manifestation symptoms, muscle fiber cross-section area reduction, associated with the altered morphological pattern and classical muscle protein degradation pathway activation, with up-regulation of FoXO1, MuRF1, and 20S proteins. On the other hand, a leucine-rich diet improved muscle strength while reducing the decline of walking and behavior, partially improving the cachexia manifestations and preventing muscle atrophy and protein degradation in Walker 256 tumor-bearing rats. Conclusions: A leucine-rich diet diminished muscle protein degradation and enhanced oxidative pathways, leading to better muscle functional performance.

scholarly journals Cancer cachexia syndrome in head and neck cancer patients: Part I. Diagnosis, impact on quality of life and survival, and treatment

Head & Neck ◽  
2007 ◽  
Vol 29 (4) ◽  
pp. 401-411 ◽  
Author(s):  
Marion Couch ◽  
Victor Lai ◽  
Trinitia Cannon ◽  
Denis Guttridge ◽  
Adam Zanation ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Cancer Cachexia ◽  
Cachexia Syndrome

scholarly journals A Prospective Randomized Controlled Trial to Study the Impact of a Nutrition-Sensitive Intervention on Adult Women With Cancer Cachexia Undergoing Palliative Care in India

2016 ◽  
Vol 16 (1) ◽  
pp. 74-84 ◽  
Author(s):  
Neha Kapoor ◽  
Jane Naufahu ◽  
Sundus Tewfik ◽  
Sushma Bhatnagar ◽  
Rakesh Garg ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Physical Activity ◽  
Body Weight ◽  
Cancer Patients ◽  
Cancer Cachexia ◽  
Controlled Trial ◽  
Intervention Group ◽  
Randomized Controlled ◽  
Nutrition Sensitive

Purpose. Advanced cancer patients with disease progression develop cachexia. Nevertheless, cancer patients at nutritional risk have shown improved body weight and quality of life with oral nutritional supplements. Method. This was a randomized controlled trial in adult female cancer patients (n = 63) attending palliative clinics, with symptoms of cachexia. Eligible patients were randomly distributed into control (n = 33) and intervention (n = 30) groups. Both groups were provided with nutritional and physical activity counseling, but the intervention group received an additional 100 g of Improved Atta (IAtta) for 6 months daily consumption. This study was designed to assess the efficacy of IAtta (with counseling) in enhancing the health status of cachexic patients. Anthropometric measurements, dietary intake, physical activity level and quality of life parameters were assessed at baseline, after 3 months, and at the end of 6 months. Results. Patients in the control group (n = 15) had significantly decreased body weight ( P = .003), mid–upper-arm circumference ( P = .002), and body fat ( P = .002) by the end of intervention. A trend of body weight gain in the intervention group (n = 17; P = .08) and significant increase of body fat ( P = .002) was observed; moreover, patients reported a significant improvement in fatigue ( P = .002) and appetite scores ( P = .006) under quality-of-life domains at the end of intervention. Conclusions. Embedding a nutrition-sensitive intervention ( IAtta ) within Indian palliative care therapy may improve quality of life and stabilize body weight in cancer cachexia patients.

scholarly journals Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lin Zhou ◽  
Tong Zhang ◽  
Wei Shao ◽  
Ruohan Lu ◽  
Lin Wang ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Drug Repositioning ◽  
Biochemical Analyses ◽  
Related Proteins ◽  
Metabolic Impairments

Abstract Background Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of the amiloride treatment for ameliorating muscle wasting in murine models of cancer cachexia. Methods The CT26 and LLC tumor cells were subcutaneously injected into mice to induce colon cancer cachexia and lung cancer cachexia, respectively. Amiloride was intraperitoneally injected daily once tumors were formed. Cachexia features of the CT26 model and the LLC model were separately characterized by phenotypic, histopathologic and biochemical analyses. Plasma exosomes and muscle atrophy-related proteins were quantitatively analyzed. Integrative NMR-based metabolomic and transcriptomic analyses were conducted to identify significantly altered metabolic pathways and distinctly changed metabolism-related biological processes in gastrocnemius. Results The CT26 and LLC cachexia models displayed prominent cachexia features including decreases in body weight, skeletal muscle, adipose tissue, and muscle strength. The amiloride treatment in tumor-bearing mice distinctly alleviated muscle atrophy and relieved cachexia-related features without affecting tumor growth. Both the CT26 and LLC cachexia mice showed increased plasma exosome densities which were largely derived from tumors. Significantly, the amiloride treatment inhibited tumor-derived exosome release, which did not obviously affect exosome secretion from non-neoplastic tissues or induce observable systemic toxicities in normal healthy mice. Integrative-omics revealed significant metabolic impairments in cachectic gastrocnemius, including promoted muscular catabolism, inhibited muscular protein synthesis, blocked glycolysis, and impeded ketone body oxidation. The amiloride treatment evidently improved the metabolic impairments in cachectic gastrocnemius. Conclusions Amiloride ameliorates cachectic muscle wasting and alleviates cancer cachexia progression through inhibiting tumor-derived exosome release. Our results are beneficial to understanding the underlying molecular mechanisms, shedding light on the potentials of amiloride in cachexia therapy.

scholarly journals Leucine-Rich Diet Improved Muscle Function in Cachectic Walker 256 Tumour-Bearing Wistar Rats

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3272
Author(s):  
Laís Rosa Viana ◽  
Gabriela de Matuoka e Chiocchetti ◽  
Lucas Oroy ◽  
Willians Fernando Vieira ◽  
Estela Natacha Brandt Busanello ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Muscle Atrophy ◽  
Muscle Function ◽  
Cancer Cachexia ◽  
Muscle Protein ◽  
Tumour Bearing ◽  
Walker 256 Tumour ◽  
Muscle Protein Degradation ◽  
Walker 256

Skeletal muscle atrophy occurs in several pathological conditions, such as cancer, especially during cancer-induced cachexia. This condition is associated with increased morbidity and poor treatment response, decreased quality of life, and increased mortality in cancer patients. A leucine-rich diet could be used as a coadjutant therapy to prevent muscle atrophy in patients suffering from cancer cachexia. Besides muscle atrophy, muscle function loss is even more important to patient quality of life. Therefore, this study aimed to investigate the potential beneficial effects of leucine supplementation on whole-body functional/movement properties, as well as some markers of muscle breakdown and inflammatory status. Adult Wistar rats were randomly distributed into four experimental groups. Two groups were fed with a control diet (18% protein): Control (C) and Walker 256 tumour-bearing (W), and two other groups were fed with a leucine-rich diet (18% protein + 3% leucine): Leucine Control (L) and Leucine Walker 256 tumour-bearing (LW). A functional analysis (walking, behaviour, and strength tests) was performed before and after tumour inoculation. Cachexia parameters such as body weight loss, muscle and fat mass, pro-inflammatory cytokine profile, and molecular and morphological aspects of skeletal muscle were also determined. As expected, Walker 256 tumour growth led to muscle function decline, cachexia manifestation symptoms, muscle fibre cross-section area reduction, and classical muscle protein degradation pathway activation, with upregulation of FoxO1, MuRF-1, and 20S proteins. On the other hand, despite having no effect on the walking test, inflammation status or muscle oxidative capacity, the leucine-rich diet improved muscle strength and behaviour performance, maintained body weight, fat and muscle mass and decreased some protein degradation markers in Walker 256 tumour-bearing rats. Indeed, a leucine-rich diet alone could not completely revert cachexia but could potentially diminish muscle protein degradation, leading to better muscle functional performance in cancer cachexia.

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