scholarly journals Prospects of 3D Bioprinting as a Possible Treatment for Cancer Cachexia

2021 ◽  
Author(s):  
Mustafa Galib ◽  
Yusha Araf ◽  
Iftekhar Bin Naser ◽  
Salman Khan Promon
Keyword(s):  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Secondary Data ◽  
3D Bioprinting ◽  
Muscle Tissues ◽  
Neural Integration ◽  
Mitochondrial Alteration ◽  
3D Printers

Cancer cachexia is a multifactorial syndrome that is identified by ongoing muscle atrophy, along with functional impairment, anorexia, weakness, fatigue, anemia, reduced tolerance to antitumor treatments. Thus, reducing the patients’ quality of life. Cachexia alone causes about 22-25% of cancer deaths. This review covers the symptoms, mediators, available treatment, and prospects of 3D bioprinting for cancer cachexia. Studies about cachexia have shown several factors that drive this disease – protein breakdown, inflammatory cytokines activation, and mitochondrial alteration. Even with proper nutrition, physical exercises, anti-inflammatory agents, chemotherapy, and grafting attempts, standard treatment has been unsuccessful for cachexia. But the use of 3D bioprinting shows much promise compared to conventional methods by attempting to fabricate 3D constructs mimicking the native muscle tissues. In this review, some 3D bioprinting techniques with their advantages and drawbacks, along with their achievements and challenges in in-vivo applications have been discussed. Constructs with neural integration or muscle-tendon units aim to repair muscle atrophy. But it is still difficult to properly bio-print these complex muscles. Although progress can be made by developing new bio-inks or 3D printers to fabricate high-resolution constructs. Using secondary data, this review study shows prospects of why 3D bioprinting can be a good alternate approach to fight cachexia.

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 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.

Development of metabolic and contractile alterations in development of cancer cachexia in female tumor-bearing mice.

2021 ◽  
Author(s):  
Seongkyun Lim ◽  
J. William Deaver ◽  
Megan E. Rosa-Caldwell ◽  
Wesley S. Haynie ◽  
Francielly Morena Da Silva ◽  
...  
Keyword(s):  
Time Course ◽  
Cancer Cachexia ◽  
Contractile Function ◽  
Tumor Bearing ◽  
Synthetic Rate ◽  
Fractional Synthetic Rate ◽  
Isometric Torque ◽  
Muscle Contractile

Cancer cachexia (CC) results in impaired muscle function and quality of life and is the primary cause of death for ~20-30% of cancer patients. We demonstrated mitochondrial degeneration as a precursor to CC in male mice, however, if such alterations occur in females is currently unknown. The purpose of this study was to elucidate muscle alterations in CC development in female tumor-bearing mice. 60 female C57BL/6J mice were injected with PBS or Lewis Lung Carcinoma at 8-week age, and tumors developed for 1, 2, 3, or 4 weeks to assess the time course of cachectic development. In vivo muscle contractile function, protein fractional synthetic rate (FSR), protein turnover, and mitochondrial health were assessed. 3- and 4-week tumor-bearing mice displayed a dichotomy in tumor growth and were reassigned to High Tumor (HT) and Low Tumor (LT) groups. HT mice exhibited lower soleus, TA, and fat weights compared to PBS. HT mice showed lower peak isometric torque and slower one-half relaxation time compared to PBS. HT mice had lower FSR compared to PBS while E3 ubiquitin ligases were greater in HT compared to other groups. Bnip3 (mitophagy) and pMitoTimer red puncta (mitochondrial degeneration) were greater in HT while Pgc1α1 and Tfam (mitochondrial biogenesis) were lower in HT compared to PBS. We demonstrate alterations in female tumor-bearing mice where HT exhibited greater protein degradation, impaired muscle contractility, and mitochondrial degeneration compared to other groups. Our data provide novel evidence for a distinct cachectic development in tumor-bearing female mice compared to previous male studies.

scholarly journals Chinese Herbal Medicine Baoyuan Jiedu Decoction Inhibited Muscle Atrophy of Cancer Cachexia through Atrogin-l and MuRF-1

2017 ◽  
Vol 2017 ◽  
pp. 1-10
Author(s):  
YaNan Zhang ◽  
XiaoChun Han ◽  
Bing Ouyang ◽  
ZhiChun Wu ◽  
HuaYun Yu ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Muscle Atrophy ◽  
Chinese Herbal Medicine ◽  
Cancer Cachexia ◽  
Life Quality ◽  
Transverse Diameter ◽  
Fiber Morphology ◽  
Chinese Herbal ◽  
Body Weights

The aim of this study is to investigate the mechanisms of Chinese herbal medicine called “Baoyuan Jiedu” (BYJD for short) decoction, improving life quality and preventing muscle atrophy of cancer cachexia model mice. We showed that the effect of BYJD decoction increased body weights of mice and reduced tumor volume and tumor mass. Furthermore, BYJD decoction increased the gastrocnemii mass and the transverse diameter of muscle fiber morphology. Moreover, BYJD reduced the expression of Atrogin-1 and MuRF-1 protein. Collectively, our results show that BYJD decoction improves the life quality of cancer cachexia mice and prevents muscle atrophy by downregulating expression of Atrogin-1 and MuRF-1.

scholarly journals Muscle-specific E3 ubiquitin ligases are involved in muscle atrophy of cancer cachexia: An in vitro and in vivo study

2015 ◽  
Vol 33 (5) ◽  
pp. 2261-2268 ◽  
Author(s):  
LEI YUAN ◽  
JUN HAN ◽  
QINGYANG MENG ◽  
QIULEI XI ◽  
QIULIN ZHUANG ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Ubiquitin Ligases ◽  
In Vivo Study ◽  
E3 Ubiquitin Ligases

scholarly journals Linalool Prevents Cisplatin Induced Muscle Atrophy by Regulating IGF-1/Akt/FoxO Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Hong Zhang ◽  
Mengyi Chi ◽  
Linlin Chen ◽  
Xipeng Sun ◽  
Lili Wan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Ring Finger ◽  
Skeletal Muscle Atrophy ◽  
Lewis Lung Cancer ◽  
Muscle Weight ◽  
C2c12 Myotube

Skeletal muscle atrophy is an important feature of cancer cachexia, which can be induced by chemotherapy, and affects the survival and quality of life of cancer patients seriously. No specific drugs for cancer cachexia have been applied in clinical practice. This study explored the therapeutic effect of linalool (LIN) on cisplatin (DDP) induced skeletal muscle atrophy. In vivo, LIN can improve skeletal muscle weight loss, anorexia, muscle strength decline and other cachexia symptoms caused by cisplatin treatment in a Lewis lung cancer tumor bearing mouse model, and cause no adverse effects on the anti-tumour effect. LIN treatment decreased the expression of muscle RING-finger protein-1 (MuRF1) and Atrogin1(MAFbx) in muscle, and the activation of insulin-like growth factor-1 (IGF-1)/protein kinase B (Akt)/forkhead box O (FoxO) pathway was observed. In vitro, LIN alleviated DDP induced C2C12 myotube atrophy, and IGF-1 receptor inhibitor Picropodophyllin (PIC), which had no adverse effect on C2C12 myotube cells, could reverse the protective effect of LIN. These results indicate that LIN down-regulates the expression of Atrogin1 and MuRF1 through the IGF-1/Akt/FoxO pathway, alleviating DDP-induced muscle atrophy and improving cachexia symptoms. LIN has the potential to be developed as a drug against cancer cachexia.

scholarly journals An Analysis of Differentially Expressed Coding and Long Non-Coding RNAs in Multiple Models of Skeletal Muscle Atrophy

2021 ◽  
Vol 22 (5) ◽  
pp. 2558
Author(s):  
Keisuke Hitachi ◽  
Masashi Nakatani ◽  
Yuri Kiyofuji ◽  
Hidehito Inagaki ◽  
Hiroki Kurahashi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Survival Rates ◽  
Skeletal Muscle Atrophy ◽  
Rna Seq ◽  
Healthy Life ◽  
Muscle Formation ◽  
Non Coding Rnas

The loss of skeletal muscle mass (muscle atrophy or wasting) caused by aging, diseases, and injury decreases quality of life, survival rates, and healthy life expectancy in humans. Although long non-coding RNAs (lncRNAs) have been implicated in skeletal muscle formation and differentiation, their precise roles in muscle atrophy remain unclear. In this study, we used RNA-sequencing (RNA-Seq) to examine changes in the expression of lncRNAs in four muscle atrophy conditions (denervation, casting, fasting, and cancer cachexia) in mice. We successfully identified 33 annotated lncRNAs and 18 novel lncRNAs with common expression changes in all four muscle atrophy conditions. Furthermore, an analysis of lncRNA–mRNA correlations revealed that several lncRNAs affected small molecule biosynthetic processes during muscle atrophy. These results provide novel insights into the lncRNA-mediated regulatory mechanism underlying muscle atrophy and may be useful for the identification of promising therapeutic targets.

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.

Shall I trust you? From child human-robot interaction to trusting relationships

2019 ◽  
Author(s):  
Cinzia Di Dio ◽  
Federico Manzi ◽  
Giulia Peretti ◽  
Angelo Cangelosi ◽  
Paul L. Harris ◽  
...  
Keyword(s):  
Behavioral Pattern ◽  
Human Robot Interaction ◽  
School Age Children ◽  
Social Relevance ◽  
Robot Interaction ◽  
Cognitive Correlates ◽  
The Social ◽  
The Relationship

Studying trust within human-robot interaction is of great importance given the social relevance of robotic agents in a variety of contexts. We investigated the acquisition, loss and restoration of trust when preschool and school-age children played with either a human or a humanoid robot in-vivo. The relationship between trust and the quality of attachment relationships, Theory of Mind, and executive function skills was also investigated. No differences were found in children’s trust in the play-partner as a function of agency (human or robot). Nevertheless, 3-years-olds showed a trend toward trusting the human more than the robot, while 7-years-olds displayed the reverse behavioral pattern, thus highlighting the developing interplay between affective and cognitive correlates of trust.

Sign in / Sign up

Export Citation Format

Share Document