JCSM rapid communications最新文献

{"title":"The relationship between computed tomography-derived body composition and survival in colorectal cancer: the effect of image software","authors":"Ross D. Dolan,&nbsp;Yu-Tzu Tien,&nbsp;Paul G. Horgan,&nbsp;Christine A. Edwards,&nbsp;Donald C. McMillan","doi":"10.1002/rco2.15","DOIUrl":"10.1002/rco2.15","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In the literature, there is considerable variation of the proportion of patients reported as having a low skeletal muscle index (SMI) (sarcopenia) or skeletal muscle radiodensity (SMD) (myosteatosis). The aim of the present study was to compare two commonly used software packages, one manual and one semi-automated to quantify body composition of patients with colorectal cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 341 patients with colorectal cancer. ImageJ and Slice-O-Matic were used to quantify the computed tomography images for total fat index, visceral obesity (visceral fat index, VFI), high subcutaneous fat index (SFI), sarcopenia (SMI), and myosteatosis (SMD). Bland–Altman analysis was conducted to test agreement of the two software programs for these indices. Survival analysis was carried out using previously defined thresholds and Cox regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In Bland–Altman analysis, ImageJ gave consistently higher values for all body composition parameters (<i>P</i> &lt; 0.001), resulting in more patients classified as high SFI (<i>P</i> &lt; 0.001) and high VFI (<i>P</i> &lt; 0.001) and fewer patients being classified as low SMI (<i>P</i> &lt; 0.0001) and SMD (<i>P</i> &lt; 0.001). The difference between SFI calculated using ImageJ and Slice-O-Matic was +7.9%. The difference between VFI, calculated using ImageJ and Slice-O-Matic, was +20.3%. The difference between low SMI and SMDs, estimated using ImageJ and Slice-O-Matic, was +2.9% and +1.2%, respectively. SFI, VFI, SMI (Dolan), SMD (Dolan), SMI (Martin), and SMD (Martin) were significantly associated with shorter overall survival using ImageJ (all <i>P</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ImageJ when compared with Slice-O-Matic gave higher values of different body composition parameters, and this impacted on the number of patients classified according to defined thresholds and their relationship with survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47971004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JCSM Rapid Communications: from basic science to clinical research","authors":"Stephan von Haehling,&nbsp;Nicole Ebner","doi":"10.1002/rco2.16","DOIUrl":"10.1002/rco2.16","url":null,"abstract":"<p>The <i>Journal of Cachexia, Sarcopenia and Muscle - Rapid Communications</i> (<i>JCSM Rapid Commun</i>) has already been launched more than one year ago and has started to publish several papers from across the spectrum of cachexia, sarcopenia, and other wasting disorders, from muscle disease like neuromuscular illness to clinical syndromes like frailty. As can be seen from the table below, the articles published so far cover a broad spectrum of topics from clinical to basic research.\u0000\u0000 </p><p>Even though the table suggests that most manuscripts stem from the basic research arena, it is our aim to cover the entire spectrum of research in wasting and muscle diseases and to provide a platform for researchers from around the globe for this area that still remains a niche of research. Indeed, topics include randomized trials such as the Auckland's Cancer Cachexia evaluating Resistance Training (ACCeRT) trial that evaluated the effects of eicosapentaenoic acid and celecoxib vs. eicosapentaenoic acid and celecoxib plus progressive resistance training followed by ingestion of essential amino acids high in leucine in patients with non-small cell lung cancer.<span>¹³</span> Other studies also cover aspects of nutritional intake like omega-3 and omega-3/curcumin-enriched fruit juices<span>¹</span> and their effects on muscle wasting or the effects of a leucine-rich diet in tumour-bearing animals.<span>⁴</span> Klose <i>et al</i>. studied stem cell activation,<span>²</span> whereas Alves <i>et al</i>. and Bekki <i>et al</i>. studied different aspects of exercise training in animal models.<span>^{7, 8}</span> Apart from publishing original research, one of our ideas is to cover different pharmacological approaches to muscle wasting in a series of dedicated review articles, one of which is presented in the current issue covering growth hormone secretagogues like anamorelin,<span>¹²</span> a substance that has received much attention recently for its ability to improve muscle mass in the ROMANA trial.<span>^{15, 16}</span> Unfortunately, anamorelin failed to improve muscle strength. Nevertheless, anamorelin follows a pharmacological concept that is used in fields as diverse as growth retardation, improvement of body composition, and gastrointestinal function, all of which are covered in the review article by Ishida <i>et al</i>.<span>¹²</span></p><p><i>JCSM Rapid Commun</i> started out of dedication to the field of wasting disorders, but also out of necessity. When we launched the mother journal, the <i>Journal of Cachexia, Sarcopenia and Muscle</i> in 2010, we did not expect such an avalanche of papers that it is currently receiving. Many very good papers still have to be rejected, simply for lack of space. However, we decided that these papers should not leave the realm of cachexia and wasting research, which gave birth to the idea of a daughter journal, <i>JCSM C","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44618458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-targeted treatment approach to cancer cachexia: Auckland's Cancer Cachexia evaluating Resistance Training (ACCeRT) trial","authors":"Elaine S. Rogers,&nbsp;Rita Sasidharan,&nbsp;Graeme M. Sequeira,&nbsp;Matthew R. Wood,&nbsp;Stephen P. Bird,&nbsp;Justin W.L. Keogh,&nbsp;Bruce Arroll,&nbsp;Joanna Stewart,&nbsp;Roderick D. MacLeod","doi":"10.1002/rco2.10","DOIUrl":"10.1002/rco2.10","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer cachexia is a condition often seen at diagnosis, throughout anti-cancer treatments and in end-stage non-small-cell lung cancer patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Participants with late-stage non-small-cell lung cancer and cachexia (defined as ≥5% weight loss within 12 months) were randomly assigned 1:2 to 2.09 g of eicosapentaenoic acid (EPA) and 300 mg of cyclo-oxygenase-2 inhibitor celecoxib orally once daily vs. same dosing of EPA, celecoxib, plus two sessions per week of progressive resistance training and 20 g of oral essential amino acids high in leucine in a split dose over 3 days, after each session. Primary endpoint was the acceptability of the earlier multi-targeted approach. Main secondary endpoints included change in body weight and fat-free mass, by bioelectric impedance analysis and total quadriceps muscle volume by magnetic resonance imaging over 20 weeks. Sixty-nine patients were screened resulting in 20 patients being enrolled. Acceptability scored high, with 4.5/5 (Arm A) and 5/5 (Arm B) for EPA and 5/5 for celecoxib within both arms and 4.8/5 for progressive resistance training sessions and 4.5/5 for essential amino acids within Arm B, all at Week 20. Results showed a net gain in bioelectric impedance analysis fat-free mass of +1.3 kg, n = 2 (Arm A), compared with +0.7 kg, n = 7 (Arm B) at Week 12, and —1.5 kg, n = 2 (Arm A), compared with —1.7 kg, n = 4 (Arm B) at Week 20. Trends in efficacy in terms of improvement and/or stability in cachexia markers were seen within magnetic resonance imaging muscle volume, albumin, and C-reactive protein levels within both arms. There were no exercise-related adverse events, with one possible related adverse event of asymptomatic atrial fibrillation in one participant within Arm A.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Non-small-cell lung cancer cachectic patients are willing to be enrolled onto a multi-targeted treatment regimen and may benefit from cachexia symptom management even during the late/refractory stage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51231062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth hormone secretagogues: history, mechanism of action, and clinical development","authors":"Junichi Ishida,&nbsp;Masakazu Saitoh,&nbsp;Nicole Ebner,&nbsp;Jochen Springer,&nbsp;Stefan D. Anker,&nbsp;Stephan von Haehling","doi":"10.1002/rco2.9","DOIUrl":"10.1002/rco2.9","url":null,"abstract":"<p>Growth hormone secretagogues (GHSs) are a generic term to describe compounds that increase growth hormone (GH) release. GHSs include agonists of the growth hormone secretagogue receptor (GHS-R), whose natural ligand is ghrelin, and agonists of the growth hormone-releasing hormone (GHRH) receptor, to which the GHRH binds as a native ligand. Several GHSs have been developed with a view to treating or diagnosing of GH deficiency, which causes growth retardation, gastrointestinal dysfunction, and altered body composition, in parallel with extensive research to identify GHRH, GHS-R, and ghrelin. This review will focus on the research history and the pharmacology of each GHS, which reached randomized clinical trials. Furthermore, we will highlight the publicly disclosed clinical trials regarding GHSs.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51232020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progesterone improves survival in hepatoma cachexia rat model","authors":"Tsuyoshi Suzuki,&nbsp;Nicole Ebner,&nbsp;Sandra Palus,&nbsp;Stephan von Haehling,&nbsp;Jochen Springer","doi":"10.1002/rco2.11","DOIUrl":"10.1002/rco2.11","url":null,"abstract":"Medroxyprogesterone and megestrol acetate are synthetic progesterone derivatives. Progestagen is an approved drug for cancer cachexia in the USA and in some European countries. These agents have been described to increase appetite and to lead to weight gain. However, the effects on survival are still unknown. The aim of this study was to evaluate the effects of progesterone on survival, cardiac function, and appetite and body weight in the Yoshida hepatoma AH‐130 rat cancer cachexia model.","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51231764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comments on prevalence and incidence of sarcopenia in the very old: findings from the Newcastle 85+ study","authors":"Dannah López-Campos,&nbsp;Fiorella Purizaga-Villarroel,&nbsp;Jorge L. Maguiña","doi":"10.1002/rco2.7","DOIUrl":"10.1002/rco2.7","url":null,"abstract":"<p>We have read the article entitled, ‘Prevalence and incidence of sarcopenia in the very old: findings from the Newcastle 85+ Study’ by Dodds et al.,<span>1</span> and it is our wish to congratulate the authors for their interesting article and, in turn, to add some contributions on the subject.</p><p>The study evaluates handgrip strength, gait speed, and lean mass as a part of the definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).<span>2</span> The handgrip strength was measured using a dynamometer, a method that is suggested by the mentioned consensus. However, when it comes to cut-off points for weak-grip strength, consensus within the EWGSOP established 20 kg for women and 30 kg for men.<span>2</span> We notice carefully that the study used the cut-off points suggested by Studenski et al.<span>3</span> which are 16 kg for women and 26 kg for men. We appreciate the use of these points, since the Studenski publication is more recent and had a larger number of participants (<i>n</i> = 26 625), including participants from different parts of the globe, such as the United States, Italy, Iceland, Puerto Rico, which allows the cut-off points to be more standardized and not directed to a single race or ethnic group.</p><p>However, we would like to emphasize that these differences in adopting a certain cut-off point can contribute to the continued misclassification of different participants in the studies and, also, that a globally accepted point, which we can use in Latin American countries, has not been established yet. This kind of misclassification can lead several studies to obtain different results and therefore contradictory conclusions.</p><p>Additionally, it is important to mention that this is a retrospective cohort study, in which the baseline prevalence and incidence of sarcopenia was determined. Logistic regression models were fitted to obtain the odds ratio (OR), instead of using the Poisson regression model to calculate the rate ratio or relative risk (RR), which is the most appropriate for a reported incidence of 10.7. Epidemiological studies show that OR may overestimate the real value of the association between variables.<span>4, 5</span></p><p>Finally, we would like to emphasize that Latin America does not have a consensus regarding the cut-off points for the measurement of the different criteria of sarcopenia, which makes it difficult to expand research studies in this specific condition. Previous publications have used the recommendations of EWGSOP. However, controversy in its application can lead to erroneous conclusions, especially when there is clear evidence of differences between the anthropometric measures of the Latin American, European, and Asian population.</p><p>The authors have no conflicts of interest.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/rco2.7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48611700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced expression of calcitonin receptor is closely associated with age-related loss of the muscle stem cell pool","authors":"Madoka Ikemoto-Uezumi,&nbsp;Akiyoshi Uezumi,&nbsp;Lidan Zhang,&nbsp;Heying Zhou,&nbsp;Naohiro Hashimoto,&nbsp;Kikuo Okamura,&nbsp;Yasumoto Matsui,&nbsp;Koji Tsukazaki,&nbsp;Tohru Hosoyama,&nbsp;Masashi Nakatani,&nbsp;Mitsuhiro Morita,&nbsp;Harumoto Yamada,&nbsp;Kunihiro Tsuchida,&nbsp;So-ichiro Fukada","doi":"10.1002/j.2617-1619.2019.tb00012.x","DOIUrl":"10.1002/j.2617-1619.2019.tb00012.x","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle regenerative capacity reduces during aging. Decline in the muscle stem cell (MuSC) pool is thought to be a cause of age-related muscle regeneration insufficiency. However, why the number of MuSCs decreases with age remains unclear. We previously found that the calcitonin receptor (Calcr) is expressed by MuSCs and plays a pivotal role in maintaining the MuSC pool. In this study, we examined whether Calcr is involved in the age-related decrease in MuSC number.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Calcr expression in MuSCs was assessed by immunofluorescence staining using muscle sections during postnatal growth and during aging. The role of Calcr during development, postnatal growth and adult stage was examined using mice conditionally deleted Calcr in myogenic lineage cells. To explore the significance of Calcr signaling on age-related changes in MuSC number, expression levels of endogenous Calcr ligands were examined. Immunohistological examination revealed that Calcr expression grew stronger as MuSCs became quiescent. Conditional Calcr deletion in early myogenic lineage cells did not affect the initial capacity of the MuSC pool, but promoted age-dependent MuSC loss. Expression of endogenous Calcr ligands remained unchanged with aging. Calcr expression in MuSCs, however, decreased significantly in aged muscle compared with young muscle in both mice and humans, and this reduction was accompanied by a loss of MuSCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study revealed significant reduction of Calcr in MuSCs with age, possibly leading to age-related loss of the MuSC pool. Thus, Calcr signaling could represent a promising target for preventing aging-associated muscle regeneration insufficiency.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/j.2617-1619.2019.tb00012.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46237274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MuRF1 and MuRF2 are key players in skeletal muscle regeneration involving myogenic deficit and deregulation of the chromatin-remodeling complex","authors":"Anselmo Sigari Moriscot,&nbsp;Igor Luchini Baptista,&nbsp;William José Silva,&nbsp;João Guilherme Silvestre,&nbsp;Volker Adams,&nbsp;Alexander Gasch,&nbsp;Julius Bogomolovas,&nbsp;Siegfried Labeit","doi":"10.1002/j.2617-1619.2019.tb00010.x","DOIUrl":"10.1002/j.2617-1619.2019.tb00010.x","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Skeletal muscle regeneration is a powerful and highly synchronized process and it is well described that intracellular pathways related to anabolic responses are readily activated. On the other hand, the role of catabolic pathways in the skeletal muscle regenerative response is much less understood. In the present study, we hypothesized that MuRF1, a key gene involved in skeletal muscle mass loss, and its close counterpart MuRF2 play a role in skeletal muscle regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Wild type, single MuRF1 knock out, single MuRF2 knock out and double MuRF1&amp;2 dKO mice had their tibialis anterior muscle injured by a single round of 4 sequential injections of cardiotoxin (CTX-10ūM, 5ūl each injection) spread along the length of the muscle. The animals were killed after 1, 3, 10 and 28 days after injury and the muscles were used to address general histology, satellite cells, myogenic markers and apoptosis. In addition, we silenced MuRF1 and MuRF2 in a primary myogenic cell culture to evaluate myogenesis and BAF57, a SWI/SNF chromatin-remodeling complex component. Finally, we employed Chromatin Immuno Precipitation assays to investigate whether MuRF1 associates with the myogenic promoters MyoD and myogenin. After cardiotoxin (CTX) injection, MuRF1 and MuRF2 expression was strongly increased and spread out inside the remaining fibers and also along satellite cells. In line with a critical role during regeneration, MuRF1&amp;2 dKO deficient injured muscles were unable to properly regenerate. In addition, dKO injured muscle failed to express activators of the myogenic program, Myf-5, FHL2 and MARP2, while myogenin levels were normally increased. Accordingly, siRNA reduced levels of MuRF1 and MuRF2 caused a severe myogenic deficit in primary myogenic cells, without any proliferation deficiency. Finally, in MuRF1&amp;2 siRNA knockdown studies and Chromatin Immuno Precipitation analysis of primary myogenic cultures we have shown an impaired nuclear clearance of BAF57 and a shortage in chromatin remodeling as a likely mechanism underlying the deficient myogenic differentiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, our results indicate a key cooperative role of the E3 ligases MuRF1 and MuRF2 in skeletal muscle regenerative response and myogenesis by inducing chromatin opening at myogenic promoters after BAF57 removal during muscle regeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/j.2617-1619.2019.tb00010.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43238141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy-induced loss of bone and muscle mass in a mouse model of breast cancer bone metastases and cachexia","authors":"Brian A. Hain,&nbsp;Haifang Xu,&nbsp;Jenna R. Wilcox,&nbsp;Daniel Mutua,&nbsp;David L. Waning","doi":"10.1002/j.2617-1619.2019.tb00011.x","DOIUrl":"10.1002/j.2617-1619.2019.tb00011.x","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chemotherapy used to treat malignancy can lead to loss of skeletal muscle mass and reduced force production, and can reduce bone volume in mice. We have shown that bone-muscle crosstalk is a key nexus in skeletal muscle function and bone homeostasis in osteolytic breast cancer bone metastases. Because chemotherapy has significant negative side effects on bone mass, and because bone loss can drive skeletal muscle weakness, we have examined the effects of chemotherapy on the musculoskeletal system in mice with breast cancer bone metastases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Six-week-old Female athymic nude mice were inoculated with 10⁵ MDA-MB231 human breast cancer cells into the left ventricle and bone metastases were confirmed by X-ray. Mice were injected with carboplatin at a dose of 60mg/kg once per week starting 4 days after tumor inoculation. Skeletal muscle was collected for biochemical analysis and extensor digitorum longus (EDL) whole muscle contractility was measured. The femur and tibia bone parameters were assessed by microCT and tumor burden in bone was determined by histology. Healthy mice treated with carboplatin lose whole body weight and have reduced individual muscle weights (gastrocnemius, tibialis anterior (TA), and EDL), reduced trabecular bone volume (BV/TV), and reduced EDL function. Mice with MDA-MB-231 bone metastases treated with carboplatin lose body weight, and have reduced EDL function as healthy mice treated with carboplatin. Mice with MDA-MB-231 bone metastases plus carboplatin do have reduced proximal tibia BV/TV compared to carboplatin alone, but carboplatin does reduce tumor burden in bone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data shows that carboplatin treatment, aimed at reducing tumor burden, contributes to cachexia and trabecular bone loss. The muscle atrophy and weakness may occur through bone-muscle crosstalk and would lead to a feed-forward cycle of musculoskeletal degradation. Despite anti-tumor effects of chemotherapy, musculoskeletal impairment is still significant in mice with bone metastases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/j.2617-1619.2019.tb00011.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42120396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy-induced loss of bone and muscle mass in a mouse model of breast cancer bone metastases and cachexia.","authors":"Brian A Hain,&nbsp;Haifang Xu,&nbsp;Jenna R Wilcox,&nbsp;Daniel Mutua,&nbsp;David L Waning","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy used to treat malignancy can lead to loss of skeletal muscle mass and reduced force production, and can reduce bone volume in mice. We have shown that bone-muscle crosstalk is a key nexus in skeletal muscle function and bone homeostasis in osteolytic breast cancer bone metastases. Because chemotherapy has significant negative side effects on bone mass, and because bone loss can drive skeletal muscle weakness, we have examined the effects of chemotherapy on the musculoskeletal system in mice with breast cancer bone metastases.</p><p><strong>Methods and results: </strong>Six-week-old Female athymic nude mice were inoculated with 10⁵ MDA-MB231 human breast cancer cells into the left ventricle and bone metastases were confirmed by X-ray. Mice were injected with carboplatin at a dose of 60mg/kg once per week starting 4 days after tumor inoculation. Skeletal muscle was collected for biochemical analysis and extensor digitorum longus (EDL) whole muscle contractility was measured. The femur and tibia bone parameters were assessed by microCT and tumor burden in bone was determined by histology. Healthy mice treated with carboplatin lose whole body weight and have reduced individual muscle weights (gastrocnemius, tibialis anterior (TA), and EDL), reduced trabecular bone volume (BV/TV), and reduced EDL function. Mice with MDA-MB-231 bone metastases treated with carboplatin lose body weight, and have reduced EDL function as healthy mice treated with carboplatin. Mice with MDA-MB-231 bone metastases plus carboplatin do have reduced proximal tibia BV/TV compared to carboplatin alone, but carboplatin does reduce tumor burden in bone.</p><p><strong>Conclusions: </strong>Our data shows that carboplatin treatment, aimed at reducing tumor burden, contributes to cachexia and trabecular bone loss. The muscle atrophy and weakness may occur through bone-muscle crosstalk and would lead to a feed-forward cycle of musculoskeletal degradation. Despite anti-tumor effects of chemotherapy, musculoskeletal impairment is still significant in mice with bone metastases.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37355577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}