Cancer cachexia (CC) is a devastating syndrome characterized by weight loss, reduced fat mass and muscle mass that affects approximately 80% of cancer patients and is responsible for 22%-30% of cancer-associated deaths. Understanding underlying mechanisms for the development of CC are crucial to advance therapies to treat CC and improve cancer outcomes. CC is a multi-organ syndrome that results in extensive skeletal muscle and adipose tissue wasting; however, CC can impair other organs such as the liver, heart, brain, and bone as well. A considerable amount of CC research focuses on changes that occur within the muscle, but cancer-related impairments in other organ systems are understudied. Furthermore, metabolic changes in organ systems other than muscle may contribute to CC. Therefore, the purpose of this review is to address degenerative mechanisms which occur during CC from a whole-body perspective. Outlining the information known about metabolic changes that occur in response to cancer is necessary to develop and enhance therapies to treat CC. As much of the current evidences in CC are from pre-clinical models we should note the majority of the data reviewed here are from pre-clinical models.
Cancer cachexia is a progressive disorder characterized by body weight, fat, and muscle loss. Cachexia induces metabolic disruptions that can be analogous and distinct from those observed in cancer, obscuring both diagnosis and treatment options. Inflammation, hypogonadism, and physical inactivity are widely investigated as systemic mediators of cancer-induced muscle wasting. At the cellular level, dysregulation of protein turnover and energy metabolism can negatively impact muscle mass and function. Exercise is well known for its anti-inflammatory effects and potent stimulation of anabolic signaling. Emerging evidence suggests the potential for exercise to rescue muscle's sensitivity to anabolic stimuli, reduce wasting through protein synthesis modulation, myokine release, and subsequent downregulation of proteolytic factors. To date, there is no recommendation for exercise in the management of cachexia. Given its complex nature, a multimodal approach incorporating exercise offers promising potential for cancer cachexia treatment. This review's primary objective is to summarize the growing body of research examining exercise regulation of cancer cachexia. Furthermore, we will provide evidence for exercise interactions with established systemic and cellular regulators of cancer-induced muscle wasting.
The process and regulation of cellular metabolism are extremely complex and accomplished through multiple signalling pathways that operate in parallel, and often experience significant overlap in upstream and downstream a signal transduction. Despite this complexity, single pathway or even single protein activations are commonly used to extrapolate broad characterizations of cellular metabolism. Furthermore, multiple routes for peptide-chain translation initiation exist, some of which may be either exclusive or overlapping depending on the state and environment of the cell. While it may be highly impractical to account for every aspect of metabolic regulation and permutation of mRNA translation, it is important to acknowledge that investigations relating to these pathways are often incomplete and not necessarily indicative of the overall metabolic status. This becomes urgent when considering the role that cellular anabolism plays in both healthy cellular functions and the aetiology of several disease's altered metabolisms. This review describes recent advances in the understanding of cellular metabolic regulation, with specific focus given to the complexity of ‘downstream’ mRNA translation initiation through both mTOR-dependent and mTOR-independent signallings.
Sarcopenia, loss of skeletal muscle and function, is a common condition among the elderly and is known to cause adverse health outcomes and increased risk of morbidity and mortality. This progressive and generalized disorder imposes a considerable socioeconomic burden. Sarcopenia is observed commonly in cancer patients. As Asia is one of the fastest aging regions in the world, it is clear that incidences of both sarcopenia and ovarian cancer will increase together in Asian countries. Ovarian cancer patients are vulnerable to develop sarcopenia during the treatment course and progress of disease, and a considerable number of patients with ovarian cancer seems to have physical inactivity and sarcopenia already at the time of diagnosis. Therefore, management of sarcopenia should be conducted together in parallel with ovarian cancer treatment and surveillance. Thus, in this article, we will review the clinical importance of sarcopenia in the aspect of ovarian cancer. Definition of sarcopenia, diagnosis, etiology, and intervention will be also introduced.
We examined bone mineral density (BMD) measurements made by dual-energy-xray-absorptiometry (DEXA) taken from 100 patients (♂46/♀54, 66±6yr) who previously underwent single total-knee arthroplasty (TKA) to determine if automated software-based artifact detection (ASAD) adequately removes implant artifact from the DXA image before analysis and if potential inaccuracies could be overcome through manual artifact correction (MAC). We also sought to determine if software-based inaccuracies would result in fracture risk misclassification (Low-BMD/Osteopenia = Young-Adult T-Score < −1). Select
When using ASAD, limbs with implants had higher BMD (+12.0 ± 1.7%, p < 0.001) compared to control limbs resulting in a 2.5 ± 0.2% overestimation of total-body BMD (single implant). Consequently, the prevalence of osteopenia in 95% of patients who would have been observed to have low leg BMD (18/19 patients) and 80% of those found to have low total-body BMD (4/5 patients) would have gone un-diagnosed. This overestimation was eliminated when using MAC. These results reveal a potential issue with ASAD for total-body DEXA scans in TKA patients and highlight the importance of careful review and MAC in those with joint replacements before making diagnostic decisions.
The pandemic of the new coronavirus (COVID-19) may be affecting the physical activity (PA) level in much of the population. This study aimed to investigate the prevalence of physical inactivity and sedentary behavior (SB) among adults with chronic diseases and their associations with sociodemographic factors during the COVID-19 pandemic. This cross-sectional study included 249 participants (age: 18-91 years; 61.4% female) with chronic conditions and attended the Family Health Strategy program in a small town in Brazil. Data were collected between 2020-07-13 and 2020-07-24 by face-to-face interviews. Self-reported PA, sitting time, chronic diseases, medication use, sociodemographic data, and self-isolation adherence were obtained by questionnaire. During this specific time point of the COVID-19 pandemic, 71.5% of participants did not meet the PA recommendations (≥500 METs-min/week), and the prevalence of SB risk (≥4 h sitting) was 62.7%. Adjusted logistic regression indicated that male participants (odds ratio [OR]: 1.89 [95% CI 1.02-3.53]), living alone (OR: 2.92 [95% CI 1.03-8.30]) or in a two-person household (OR: 2.32 [95% CI 1.16-4.63]), and those who reported sometimes performing self-isolation (OR: 3.07 [95% CI 1.47-6.40]) were more likely to meet the minimum PA recommendations. Current smokers had a lower odds (OR: 0.36 [95% CI 0.14-0.95]) of meeting the PA recommendations. Older participants (OR: 2.18 [95% CI 1.06-4.50]) and those who had multimorbidity (OR: 1.92 [95% CI 1.07-3.44]) were more likely to have a higher degree of SB. There is an urgent need to mitigate physical inactivity and SB, and public health interventions must take into account sociodemographic status.
Ever since the outbreak of Coronavirus disease 2019 (COVID-19) in late 2019, it has killed millions of people worldwide. Even people not stricken by this disease are not spared from its negative economic, social, and health-related drawbacks. This commentary provides insight into the potential mechanisms involved in the development of depression and emotional negativity escalating during the current pandemic. In particular, preventive measures of COVID-19, such as staying at home, are sedentarism measures that decrease physical activity. Physical inactivity alters gut microbiome structure in a fashion that promotes gut dysbiosis and flaring of systemic inflammation, leading to the buildup of body fat. Obesity, which contributes to a trail of health-depleting disorders, furthers gut microbial disintegration while fat tissue stimulates the release of cytokines, promotes metabolic resistance, and alters signaling involved in the production of antioxidants. As a result, the body gets flooded by toxic molecules such pro-inflammatory mediators, free radicals, and advanced glycation end products. These toxic molecules alter cellular function in all body tissues, including those of the brain. Neuroinflammation is associated with progressive declines in cognitive and motor functions along with dysregulation in emotions. Counteracting the sedentarism enforced by the COVID-19 pandemic through the participation in suitable indoors activities and the intake of healthy food is likely to protect against or revert physiological impairments that may affect people retreating to their homes during the current crisis, eventually restoring physical and mental health.