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Nutrition: Diet Therapy and Nutritional Supplements
Published in Paloma Tejero, Hernán Pinto, Aesthetic Treatments for the Oncology Patient, 2020
There are a series of metabolic and endocrine changes that generate a catabolic state in which lipolysis and proteolysis are induced, resulting in loss of lean mass, fat, and insulin resistance. Tumor factors (generated by the tumor itself): Proteolysis-inducing factor (PIF) or lipid mobilization factor.Humoral factors (generated by the host in response to the presence of the tumor): Cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1 and IL-6, and interferon [IFN]-γ), neuropeptides (neuropeptide Y, serotonin, and melanocortins), and hormones (insulin and glucagon). In these cases, cancer induces anorexia by producing substances with remote effect on the central nervous system and without mechanical involvement of the digestive tract. For example, there are tumors that can produce substances that alter the perception of taste, generating an aversion toward meat (traditionally described in gastric cancer). Various mechanisms have been proposed to explain these situations. In this sense, various substances have been involved that exert a peripheral effect on neuroendocrine cells or directly on the hypothalamus, causing anorexia.
ß-hydroxy-ß-methylbutyrate
Published in Jay R Hoffman, Dietary Supplementation in Sport and Exercise, 2019
The ubiquitin-proteasome pathway (UPP) is considered the primary avenue for protein catabolism in mammals. HMB has been shown to reduce muscle protein degradation by diminishing the UPP partially by inhibition of a protein called proteolysis-inducing factor (PIF) (67). PIF has been noted as a cachectic (body weakening or wasting) indicator as it is elevated in cancer patients and people experiencing losses in lean body mass (34). Ubiquitin-proteasome signalling is regulated by an intricate array of processes and has profound cellular effects ranging from apoptosis (programmed cell death) to cell differentiation and regeneration. In fact, when human myoblasts were treated with HMB in vitro, the number of apoptotic cells were reduced, there were higher levels of anti-apoptotic proteins Bcl-2 and lower levels of the pro-apoptotic protein BAX (38). This is supported in animal models showing that HMB is an inhibitor of myonuclear apoptosis by regulating mitochondrial-associated caspase signalling, a prominent component of the apoptotic pathway (26). Considering the addition of new myonuclei is presumed to be necessary to promote muscle hypertrophy and the maintenance of these nuclei are vital to preserving muscle mass in catabolic conditions, this is likely the principal mechanism underpinning reductions of muscle protein breakdown observed in humans via HMB supplementation.
Development of palliative medicine in the United Kingdom and Ireland
Published in Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita, Textbook of Palliative Medicine and Supportive Care, 2015
NF-kB is a transcriptional factor that regulates the expression of many genes involved in inflammation including cyclooxygenase inhibitors (COX-2), nitric oxide synthase, TNF\alpha, andIL-6. NF-kB is also involved in many aspects of oncogenesis and apoptosis and is considered a potential antitumor target, even though NF-kB inhibition carries a theoretical risk of immunosuppression, given its critical role in innate and adaptive immune responses. Â 53 As regards muscle atrophy, TNF- α inhibits myogenesis in vitro by activating NF-kB, which leads to degradation of MyoD transcripts. Â 54 More recently in a mouse model of cancer cachexia, two novel drugs were tested that specifically inhibited NF-kB by targeting the IkB kinase (IKK) complex. The drugs prevented the development of tumor-induced systolic dysfunction and atrophy. Â 55NF-kB also appears to be essential in the proteolysis-inducing factor (PIF)induced expression of the ubiquitin-proteasome pathway. Â 56
Promising models for cancer-induced cachexia drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Tsuyoshi Suzuki, Stephan Von Haehling, Jochen Springer
This widely used model has a major drawback in its excessive tumor burden. After inoculation of 2 × 107 Walker 256 cells, the tumor weight reached 19 g and animals displayed cancer cachexia [46]. The tumor mass increased to 40.46 g ± 3.31 g or approximately 15% of the body weight after 21 days [47]. Beluzi et al. [48] reported a tumor weight of approximately 80 g in rats weighing approximately 280 g 26 days after tumor inoculation. The huge tumor burden that can reach up to 50% of body weight [33] makes the use of the Walker256 model very problematic for ethical reasons and because the tumor mass in humans is typically below 1% of body weight. However, the Walker 256 model resembles major cancer cachexia characteristics seen in the clinic including the loss of body weight comprised both fat and muscle mass wasting, anorexia, and systemic inflammation. A unique proteolysis-inducing factor (PIF)-like molecule has been purified from ascitic fluid of Walker tumor-bearing rats termed Walker factor (WF), was able to induce atrophy in C2C12 myotubes [49]. Overall, using this model is not advisable due to the extremely high disease burden.
Lessons learned from the discovery and development of the sesquiterpene lactones in cancer therapy and prevention
Published in Expert Opinion on Drug Discovery, 2022
Israa A. Cheikh, Chirine El-Baba, Ali Youssef, Najat A. Saliba, Akram Ghantous, Nadine Darwiche
The first phase 1 cancer clinical study on atractylenolide 1 revealed that 1.32 gm/day administration of the drug for seven weeks could alleviate the symptoms of cachexia in patients with stomach cancer by preventing the degradation of proteolysis-inducing factor by raising TNF-α and decreasing IL-1 levels (CN-00708107) [223]. A phase 2 clinical trial is currently at the prospective registration to establish the dose, pharmacokinetics, safety, immunomodulatory activity, and of the standardized extract of Atractylodes lancea, a source of atractylenolide 1, in patients with unresectable or metastatic liver tumor (TCTR20210129007).