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. Other events, such as alterations in the rate of myogenesis/apoptosis and decreased regeneration potential also affect skeletal muscle in patients with cancer. Mitochondrial dysfunction also contributes to changes in skeletal muscle metabolism and further contributes to the exacerbation of the cancer-wasting syndrome. Different inflammatory mediators either released by the tumor or by the patient's healthy cells are responsible for the activation of these catabolic processes that take place in skeletal muscle and in other tissues/organs, such as liver or adipose tissues. Indeed, white adipose tissue is also subject to extensive wasting and 'browning' of some of the white adipocytes into beige cells; therefore increasing the energetic inefficiency of the patient with cancer. Recently, an interest in the role of micromRNAs either free or transported into exosomes has been related to the events that take place in white adipose tissue during cancer cachexia

Journal of Physics: Conference Series

Lightweight designs and demanding safety requirements in automotive industry are increasingly promoting the use of Advanced High Strength Steel (AHSS) sheets. Such steels present higher strength (above 800 MPa) but lower ductility than conventional steels. Their great properties allow the reduction of the thickness of automobile structural components without compromising the safety, but also introduce new challenges to parts manufacturers. The fabrication of most cold formed components starts from shear cut blanks and, due to the lower ductility of AHSS, edge cracking problems can appear during forming operations, forcing the stop of the production and slowing down the industrial process. Forming Limit Diagrams (FLD) and FEM simulations are very useful tools to predict fracture problems in zones with high localized strain, but they are not able to predict edge cracking. It has been observed that the fracture toughness, measured through the Essential Work of Fracture (EWF) methodology, is a good indicator of the stretch flangeability in AHSS and can help to foresee this type of fractures. In this work, a serial production automotive component has been studied. The component showed cracks in some flanged edges when using a dual phase steel. It is shown that the conventional approach to explain formability, based on tensile tests and FLD, fails in the prediction of edge cracking. A new approach, based on fracture mechanics, help to solve the problem by selecting steel grades with higher fracture toughness, measured by means of EWF. Results confirmed that fracture toughness, in terms of EWF, can be readily used as a material parameter to rationalize cracking related problems and select AHSS with improved edge cracking resistance.Peer ReviewedPostprint (published version

Are there any benefits of exercise training in cancer cachexia?

Cancer cachexia is a complex syndrome characterized by inflammation, body weight loss, muscle, and adipose tissue wasting that is responsible for the death of a considerable percentage of cancer patients. In addition, during cachexia muscle strength and endurance are dramatically reduced, limiting the ability to perform daily activities and severely affecting the patient’s quality of life. Different studies have emphasized that a single therapy may not be completely successful in the treatment of cachexia. Beyond pharmacological strategies, exercise training has been suggested as a promising countermeasure to prevent cachexia, in order to restore both strength and endurance, depending on the type of exercise. Unfortunately, a small number of studies, in both clinical and experimental settings, have been performed to date. Moreover, when considering exercise in cancer, several factors have to be taken into consideration, in particular those alterations that could limit the capacity to perform exercise and consequently the resulting beneficial or detrimental effects. This editorial is aimed at stimulating the debate on the suitability of including exercise training in a multi-functional approach against cachexia taking into consideration both limitations and advantages

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. Bearing all this in mind, the aim of the present review is to examine the impact of nonmuscle tissues in cancer cachexia

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. Among the most promising approaches we can include the use of ghrelin agonists, beta-blockers, beta-adrenergic agonists, androgen receptor agonists and anti-myostatin peptides. The multi-targeted approach seems essential in these treatments, which should include the combination of both nutritional support, drugs and a suitable program of physical exercise, in order to ameliorate both anorexia and the metabolic changes associated with cachexia. In addition, another very important and crucial aspect to be taken into consideration in the design of clinical trials for the treatment of cancer cachexia is to staging cancer patients in relation with the degree of cachexia, in order to start as early as possible this triple approach in the course of the disease, even before the weight loss can be detected

Identification of fracture toughness parameters to understand the fracture resistance of advanced high strength sheet steels

The fracture toughness of four advanced high strength steel (AHSS) thin sheets is evaluated through different characterization methodologies, with the aim of identifying the most relevant toughness parameters to describe their fracture resistance. The investigated steels are: a Complex Phase steel, a Dual Phase steel, a Trip-Aided Bainitic Ferritic steel and a Quenching and Partitioning steel. Their crack initiation and propagation resistance is assessed by means of J-integral measurements, essential work of fracture tests and Kahn-type tear tests. The results obtained from the different methodologies are compared and discussed, and the influence of different parameters such as specimen geometry or notch radius is investigated. Crack initiation resistance parameters are shown to be independent of the specimen geometry and the testing method. However, significant differences are found in the crack propagation resistance values. The results show that, when there is a significant energetic contribution from necking during crack propagation, the specific essential work of fracture (we) better describes the overall fracture resistance of thin AHSS sheets than JC. In contrast, energy values obtained from tear tests overestimate the crack propagation resistance and provide a poor estimation of AHSS fracture performance. we is concluded to be the most suitable parameter to describe the global fracture behaviour of AHSS sheets and it is presented as a key property for new material design and optimization.Peer ReviewedPostprint (author's final draft

CASCO Questionnaire (c)

For full access to the document please contact: [email protected]

Biological mechanism-based and patient-centered management of cancer-related symptoms and syndromes

In recent years, full recovery rates for cancer patients significantly increased and mean survival improved. Moreover, chronicization of cancer disease and concerns about aggressive care close to the end-of-life raised the awareness of better risk-benefit balancing. [...

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. We carried out a case -control study that enrolled prospectively 186 cancer patients and 95 age-matched controls. The score includes five components: (1) body weight loss and composition, (2) inflammation/metabolic disturbances/immunosuppression, (3) physical performance, (4) anorexia, and (5) quality of life. The present study provides clinical validation for the use of the score. In order to show the metric properties of CASCO, three different groups of cachectic cancer patients were established according to the results obtained with the statistical approach used: mild cachexia (15 ≤ × ≤ 28), moderate cachexia (29 ≤ × ≤ 46), and severe cachexia (47 ≤ × ≤ 100). In addition, a simplified version of CASCO, MiniCASCO (MCASCO), was also presented and it contributes as a valid and easy-to-use tool for cachexia staging. Significant statistically correlations were found between CASCO and other validated indexes such as Eastern Cooperative Oncology Group (ECOG) and the subjective diagnosis of cachexia by specialized oncologists. A very significant estimated correlation between CASCO and MCASCO was found that suggests that MCASCO might constitute an easy and valid tool for the staging of the cachectic cancer patients. CASCO and MCASCO provide a new tool for the quantitative staging of cachectic cancer patients with a clear advantage over previous classifications