Neuregulin 4 Downregulation Alters Mitochondrial Morphology and Induces Oxidative Stress in 3T3-L1 Adipocytes.

Neuregulin 4 (Nrg4) is an adipokine that belongs to the epidermal growth factor family and binds to ErbB4 tyrosine kinase receptors. In 3T3-L1 adipocytes, the downregulation of expression enhances inflammation and autophagy, resulting in insulin resistance. Here, we searched for the causes of this phenotype.

Anabolic deficits and divergent unfolded protein response underlie skeletal and cardiac muscle growth impairments in the Yoshida hepatoma tumor model of cancer cachexia.

Cancer cachexia manifests as whole body wasting, however, the precise mechanisms governing the alterations in skeletal muscle and cardiac anabolism have yet to be fully elucidated. In this study, we explored changes in anabolic processes in both skeletal and cardiac muscles in the Yoshida AH-130 ascites hepatoma model of cancer cachexia. AH-130 tumor-bearing rats experienced significant losses in body weight, skeletal muscle, and heart mass.

Formoterol reduces muscle wasting in mice undergoing doxorubicin chemotherapy.

Background: Even though doxorubicin (DOX) chemotherapy promotes intense muscle wasting, this drug is still widely used in clinical practice due to its remarkable efficiency in managing cancer. On the other hand, intense muscle loss during the oncological treatment is considered a bad prognosis for the disease's evolution and the patient's quality of life. In this sense, strategies that can counteract the muscle wasting induced by DOX are essential.

Effects of S-pindolol in mouse pancreatic and lung cancer cachexia models.

Background: It is known that S-pindolol attenuates muscle loss in animal models of cancer cachexia and sarcopenia. In cancer cachexia, it also significantly reduced mortality and improved cardiac function, which is strongly compromised in cachectic animals.

Methods: Here, we tested 3 mg/kg/day of S-pindolol in two murine cancer cachexia models: pancreatic cancer cachexia (KPC) and Lewis lung carcinoma (LLC).

Effect of Cancer-Related Cachexia and Associated Changes in Nutritional Status, Inflammatory Status, and Muscle Mass on Immunotherapy Efficacy and Survival in Patients with Advanced Non-Small Cell Lung Cancer.

Immune checkpoint inhibitor (ICI)-based immunotherapy has significantly improved the survival of patients with advanced non-small cell lung cancer (NSCLC); however, a significant percentage of patients do not benefit from this approach, and predictive biomarkers are needed. Increasing evidence demonstrates that cachexia, a complex syndrome driven by cancer-related chronic inflammation often encountered in patients with NSCLC, may impair the immune response and ICI efficacy. Herein, we carried out a prospective study aimed at evaluating the prognostic and predictive role of cachexia with the related changes in nutritional, metabolic, and inflammatory parameters (assessed by the multidimensional miniCASCO tool) on the survival and clinical response (i.

Cancer-associated cachexia - understanding the tumour macroenvironment and microenvironment to improve management.

Cachexia is a devastating, multifactorial and often irreversible systemic syndrome characterized by substantial weight loss (mainly of skeletal muscle and adipose tissue) that occurs in around 50-80% of patients with cancer. Although this condition mainly affects skeletal muscle (which accounts for approximately 40% of total body weight), cachexia is a multi-organ syndrome that also involves white and brown adipose tissue, and organs including the bones, brain, liver, gut and heart. Notably, cachexia accounts for up to 20% of cancer-related deaths.

Lack of Synergy Between β-Agonist Treatment and a Blockage of Sarcoplasmic Calcium Flow in a Rat Cancer Cachexia Model.

Background: During cancer cachexia, both skeletal muscle and adipose tissue losses take place. The use of β2-agonists, formoterol in particular, has proven to be very successful in the treatment of the syndrome in pre-clinical models. The object of the present research was to study the effects of a combination of formoterol and dantrolene, an inhibitor of the ryanodine receptor 1 (RyR1), on body weight loss and cachexia in tumour-bearing animals.

A small Cretaceous crocodyliform in a dinosaur nesting ground and the origin of sebecids.

Sebecosuchia was a group of highly specialized cursorial crocodyliforms that diversified during the Cretaceous and persist until the end of the Miocene. Their unique combination of cranial and post-cranial features indicates that they were active terrestrial predators that occupied the apex of the Late Cretaceous terrestrial ecosystems, even competing with theropod dinosaurs. Here, we report the discovery of the earliest sebecid worldwide, and the first from Eurasia, Ogresuchus furatus gen.

The animal cachexia score (ACASCO).

Background: None of the published studies involving cancer cachexia experimental models have included a measure of the severity of the syndrome like the scoring system previously developed for human subjects. The aim of the present investigation was to define and validate a cachexia score usable in both rat and mouse tumor models.

Methods: In order to achieve this goal, we included in the study one rat model (Yoshida AH-130ascites hepatoma) and two mouse models (Lewis lung carcinoma and Colon26 carcinoma).

Differential structural features in soleus and gastrocnemius of carnitine-treated cancer cachectic rats.

Muscle wasting is associated with chronic diseases and cancer. Elucidation of the biological mechanism involved in the process of muscle mass loss and cachexia may help identify therapeutic targets. We hypothesized that l-carnitine treatment may differentially revert muscle fiber atrophy and other structural alterations in slow- and fast-twitch limb muscles of rats bearing the Yoshida ascites hepatoma.

Mediators of cachexia in cancer patients.

Alterations in amino acid and protein metabolism-particularly in skeletal muscle-are a key feature of cancer that contributes to the cachexia syndrome. Thus, skeletal muscle protein turnover is characterized by an exacerbated rate of protein degradation, promoted by an activation of different proteolytic systems that include the ubiquitin-proteasome and the autophagic-lysosomal pathways. These changes are promoted by both hormonal alterations and inflammatory mediators released as a result of the systemic inflammatory response induced by the tumor.

Therapeutic strategies against cancer cachexia.

Cancer cachexia has two main components: anorexia and metabolic alterations. The main changes associated with the development of this multi-organic syndrome are glucose intolerance, fat depletion and muscle protein hypercatabolism. The aim of this paper is to review the more recent therapeutic approaches designed to counteract the wasting suffered by the cancer patient with cachexia.

Cancer cachexia, a clinical challenge.

Purpose Of Review: The aim of this article is to review the metabolic background of the cachectic syndrome and to analyze the recent therapeutic approaches designed to counteract the wasting suffered by the cancer patient with cachexia.

Recent Findings: The main changes associated with the development of this multiorganic syndrome are glucose intolerance, fat depletion and muscle protein hypercatabolism. Among the most promising approaches for the treatment of cachexia include the use of ghrelin agonists, beta-blockers, beta-adrenergic agonists, androgen receptor agonists and antimyostatin peptides.

Inter-tissue communication in cancer cachexia.

Cachexia is a systemic condition that occurs during many neoplastic diseases, such as cancer. Cachexia in cancer is characterized by loss of body weight and muscle and by adipose tissue wasting and systemic inflammation. Cancer cachexia is often associated with anorexia and increased energy expenditure.

Effects of the beta agonist formoterol on atrophy signaling, autophagy, and muscle phenotype in respiratory and limb muscles of rats with cancer-induced cachexia.

Muscle mass loss and wasting are characteristic features of patients with chronic conditions including cancer. Beta-adrenoceptors attenuate muscle wasting. We hypothesized that specific muscle atrophy signaling pathways and altered metabolism may be attenuated in cancer cachectic animals receiving treatment with the beta agonist formoterol.

Formoterol attenuates increased oxidative stress and myosin protein loss in respiratory and limb muscles of cancer cachectic rats.

Muscle mass loss and wasting are characteristic features of patients with chronic conditions including cancer. Therapeutic options are still scarce. We hypothesized that cachexia-induced muscle oxidative stress may be attenuated in response to treatment with beta-adrenoceptor-selective agonist formoterol in rats.

Novel targeted therapies for cancer cachexia.

Anorexia and metabolic alterations are the main components of the cachectic syndrome. Glucose intolerance, fat depletion, muscle protein catabolism and other alterations are involved in the development of cancer cachexia, a multi-organ syndrome. Nutritional approach strategies are not satisfactory in reversing the cachectic syndrome.

A Rat Immobilization Model Based on Cage Volume Reduction: A Physiological Model for Bed Rest?

Bed rest has been an established treatment in the past prescribed for critically illness or convalescing patients, in order to preserve their body metabolic resource, to prevent serious complications and to support their rapid path to recovery. However, it has been reported that prolonged bed rest can have detrimental consequences that may delay or prevent the recovery from clinical illness. In order to study disuse-induced changes in muscle and bone, as observed during prolonged bed rest in humans, an innovative new model of muscle disuse for rodents is presented.

Validation of the CAchexia SCOre (CASCO). Staging Cancer Patients: The Use of miniCASCO as a Simplified Tool.

The CAchexia SCOre (CASCO) was described as a tool for the staging of cachectic cancer patients. The aim of this study is to show the metric properties of CASCO in order to classify cachectic cancer patients into three different groups, which are associated with a numerical scoring. The final aim was to clinically validate CASCO for its use in the classification of cachectic cancer patients in clinical practice.

A multifactorial anti-cachectic approach for cancer cachexia in a rat model undergoing chemotherapy.

Background: The effectiveness of drugs aimed at counteracting cancer cachexia is generally tested in pre-clinical rodent models, where only the tumour-induced alterations are taken into account, excluding the co-presence of anti-tumour molecules that could worsen the scenario and/or interfere with the treatment.

Methods: The aim of the present investigation has been to assess the efficacy of a multifactorial treatment, including formoterol and megestrol acetate, in cachectic tumour-bearing rats (Yoshida AH-130, a highly cachectic tumour) undergoing chemotherapy (sorafenib).

Results: Treatment of cachectic tumour-bearing rats with sorafenib (90 mg/kg) causes an important decrease in tumour cell content due to both reduced cell proliferation and increased apoptosis.

Combination of exercise training and erythropoietin prevents cancer-induced muscle alterations.

Cancer cachexia is a syndrome characterized by loss of skeletal muscle mass, inflammation, anorexia and anemia, contributing to patient fatigue and reduced quality of life. In addition to nutritional approaches, exercise training (EX) has been proposed as a suitable tool to manage cachexia. In the present work the effect of mild exercise training, coupled to erythropoietin (EPO) administration to prevent anemia, has been tested in tumor-bearing mice.

Complete reversal of muscle wasting in experimental cancer cachexia: Additive effects of activin type II receptor inhibition and β-2 agonist.

Formoterol is a highly potent β2-adrenoceptor-selective agonist, which is a muscle growth promoter in many animal species. Myostatin/activin inhibition reverses skeletal muscle loss and prolongs survival of tumor-bearing animals. The aim of this investigation was to evaluate the effects of a combination of the soluble myostatin receptor ActRIIB (sActRIIB) and the β2-agonist formoterol in the cachectic Lewis lung carcinoma model.

Nonmuscle Tissues Contribution to Cancer Cachexia.

Cachexia is a syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting, and inflammation, being often associated with anorexia. In spite of the fact that muscle tissue represents more than 40% of body weight and seems to be the main tissue involved in the wasting that occurs during cachexia, recent developments suggest that tissues/organs such as adipose (both brown and white), brain, liver, gut, and heart are directly involved in the cachectic process and may be responsible for muscle wasting. This suggests that cachexia is indeed a multiorgan syndrome.