Nutritional therapy for cancer cachexia (original) (raw)
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What Role Do Inflammatory Cytokines Play in Cancer Cachexia?
Cureus
A tumor extends its effects beyond its local site, and one such effect is cancer cachexia which is caused by a state of systemic inflammation in response to cancer. Though the prominent effect of cancer cachexia is seen on skeletal muscles, it shows deterioration in other organs' smooth muscle, adipose tissue, blood, bone marrow, liver, and immunity. Interleukin (IL)-6 plays an imminent role along with tissue necrosis factoralpha, IL-1 beta, interferon-gamma, myostatin, adiponectin, growth differentiation factor-15, activin A, etc. These cytokines through nuclear factor-kappa beta, mitogen-activated protein kinase, suppressor of mothers against decapentaplegic, and Janus activated kinase/signal transducer and activator of transcription pathway activate genes inducing ubiquitin-proteosome system and reactive oxidative species. Apart from these, they participate in causing anemia and immunosuppression. Adipose tissue acts as a source of cytokines and place of action of cytokines leading to lipolysis. Moreover, these cytokines act at the hypothalamic-pituitary-adrenal axis change metabolism and add to anorexia which already exists in cancer patients. The involvement of multiple cytokines necessitates the development and testing of anti-cytokines in combinations.
Inflammation and cancer: how friendly is the relationship for cancer patients?
Current Opinion in Pharmacology, 2009
Evidence has emerged in the last two decades that at the molecular level most chronic diseases, including cancer, are caused by a dysregulated inflammatory response. The identification of transcription factors such as NF-kB, AP-1 and STAT3 and their gene products such as tumor necrosis factor, interleukin-1, interleukin-6, chemokines, cyclooxygenase-2, 5 lipooxygenase, matrix metalloproteases, and vascular endothelial growth factor, adhesion molecules and others have provided the molecular basis for the role of inflammation in cancer. These inflammatory pathways are activated by tobacco, stress, dietary agents, obesity, alcohol, infectious agents, irradiation, and environmental stimuli, which together account for as much as 95% of all cancers. These pathways have been implicated in transformation, survival, proliferation, invasion, angiogenesis, metastasis, chemoresistance, and radioresistance of cancer, so much so that survival and proliferation of most types of cancer stem cells themselves appear to be dependent on the activation of these inflammatory pathways. Most of this evidence, however, is from preclinical studies. Whether these pathways have any role in prevention, progression, diagnosis, prognosis, recurrence or treatment of cancer in patients, is the topic of discussion of this review. We present evidence that inhibitors of inflammatory biomarkers may have a role in both prevention and treatment of cancer.
Targeting inflammatory pathways by dietary agents for prevention and therapy of cancer
Journal of Food and Drug Analysis, 2020
Chronic infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and high-calorie diet have been recognized as major risk factors for the most common types of cancers. All these risk factors are linked to cancer through inflammation. While acute inflammation that persists for short-term mediates host defense against infections, chronic inflammation that lasts for long-term can predispose the host to various chronic illnesses, including cancer. Linkage between cancer and inflammation is indicated by numerous lines of evidence; first, transcription factors NF-B and STAT3, two major pathways for inflammation, are activated by most cancer risk factors; second, an inflammatory condition precedes most cancers; third, NF-B and STAT3 are constitutively active in most cancers; fourth, hypoxia and acidic conditions found in solid tumors activate NF-B; fifth, chemotherapeutic agents and gamma irradiation activate NF-B and lead to chemo-resistance and radio-resistance; sixth, most gene products linked to inflammation, survival, proliferation, invasion, angiogenesis, and metastasis are regulated by NF-B and STAT3; seventh, suppression of NF-B and STAT3 inhibits the proliferation and invasion of tumors; and eighth, most chemo-preventive agents mediate their effects through inhibition of NF-B and STAT3 activation pathways. Thus suppression of these pro-inflammatory pathways may provide opportunities for both prevention and treatment of cancer. The potential of dietary agents in regulation of these inflammatory cell signaling pathways and their role in prevention and therapy of cancer, is discussed.
Clinical Cancer Research, 2009
Chronic infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and high-calorie diet have been recognized as major risk factors for the most common types of cancer. All these risk factors are linked to cancer through inflammation. Although acute inflammation that persists for short-term mediates host defense against infections, chronic inflammation that lasts for long term can predispose the host to various chronic illnesses, including cancer. Linkage between cancer and inflammation is indicated by numerous lines of evidence; first, transcription factors nuclear factor-κB (NF-κB) and signal transducers and activators of transcription 3 (STAT3), two major pathways for inflammation, are activated by most cancer risk factors; second, an inflammatory condition precedes most cancers; third, NF-κB and STAT3 are constitutively active in most cancers; fourth, hypoxia and acidic conditions found in solid tumors activate NF-κB; fifth, chemotherapeutic agents and γ-irradia...
Cancer and Inflammation: Promise for Biologic Therapy
Journal of Immunotherapy, 2010
Cancers often arise as the end stage of inflammation in adults, but not in children. As such there is a complex interplay between host immune cells during neoplastic development, with both an ability to promote cancer and limit or eliminate it, most often complicit with the host. In humans, defining inflammation and the presence of inflammatory cells within or surrounding the tumor is a critical aspect of modern pathology. Groups defining staging for neoplasms are strongly encouraged to assess and incorporate measures of the presence of apoptosis, autophagy, and necrosis and also the nature and quality of the immune infiltrate. Both environmental and genetic factors enhance the risk of cigarette smoking, Helicobacter pylori, hepatitis B/C, human papilloma virus, solar irradiation, asbestos, pancreatitis, or other causes of chronic inflammation. Identifying suitable genetic polymorphisms in cytokines, cytokine receptors, and Toll-like receptors among other immune response genes is also seen as high value as genomic sequencing becomes less expensive. Animal models that incorporate and assess not only the genetic anlagen but also the inflammatory cells and the presence of microbial pathogens and damage-associated molecular pattern molecules are necessary. Identifying micro-RNAs involved in regulating the response to damage or injury are seen as highly promising. Although no therapeutic strategies to prevent or treat cancers based on insights into inflammatory pathways are currently approved for the common epithelial malignancies, there remains substantial interest in agents targeting COX2 or PPARg, ethyl pyruvate and steroids, and several novel agents on the horizon.
On the Inflammation Theory of Cancer
Cancer therapy & Oncology International Journal, 2017
A recent clinical trial on humans (CANTOS) aimed to test inflammation, one of the two major theories for cardiovascular diseases, the other theory being concerned with lipids. However, somewhat surprisingly, the trial provided some support for the inflammation theory of cancer and this result may overshadow the trial's original aim. However, inflammation has long been linked to cancer. As a preface to the link between inflammation and cancer, I first review the trial and summarize its results within the context of secondary prevention and mechanism pathways. With different doses against placebo, the drug tested in the trial was Canakinumab, a monoclonal antibody that targets Interleukin-1β. From a personalized medicine's perspective, the trial and its results point to the future of secondary prevention as the identification of which mechanistic pathway would be most beneficial for a given patient. From this viewpoint, inflammation today is very much analogous to the identification of cholesterol 30 years ago. We now need to distinguish those heart disease patients who have "residual cholesterol risk" from those who have "residual inflammatory risk", or both. These two groups will require different, perhaps also simultaneous, interventions. Now, many malignancies arise in areas of chronic inflammation and inadequate resolution of inflammation could have a major role in tumor invasion, progression, and metastasis although it may not play a role in oncogenesis. Inflammation is of particular path physiological relevance in lung cancer in that chronic bronchitis, triggered by asbestos, silica, smoking, and other external inhaled toxins, results in a persistent inflammatory response. To interpret the trial results in terms of cancer, inflammation in the tumor microenvironment mediated by IL-1β was hypothesized to have a major role in cancer invasiveness, progression, and metastasis. This, in turn, suggests that IL-1β participates in the invasiveness of already existing malignancies. Thus, inhibition of IL-1β might have an adjunctive role in the treatment of cancers that have at least a partial inflammatory basis. This is the first evidence that inhibition of IL-1β with the monoclonal antibody Canakinumab is associated with reduced incidences of fatal cancer, lung cancer, and fatal lung cancer. The trial also showed an apparent decrease in the risk of cancer. Unfortunately, it was also associated with a higher incidence of fatal infection. Thus, anti-inflammatory therapy with Canakinumab targeting the IL-1β innate immunity pathway could significantly reduce incident lung cancer and lung cancer mortality. Nonetheless, these results should be replicated and extended in formal settings of cancer screening and treatment. They should also be directly related to early cancer screening and initial treatment, particularly in lung cancer.
Cancer as a Proinflammatory Environment: Metastasis and Cachexia
Mediators of Inflammation, 2015
The development of the syndrome of cancer cachexia and that of metastasis are related with a poor prognostic for cancer patients. They are considered multifactorial processes associated with a proinflammatory environment, to which tumour microenvironment and other tissues from the tumour bearing individuals contribute. The aim of the present review is to address the role of ghrelin, myostatin, leptin, HIF, IL-6, TNF-α, and ANGPTL-4 in the regulation of energy balance, tumour development, and tumoural cell invasion. Hypoxia induced factor plays a prominent role in tumour macro- and microenvironment, by modulating the release of proinflammatory cytokines.
Cancer research, 2000
MCG 101 tumors were implanted sc. on wild-type C57 Bl and gene knockout mice to evaluate the role of host-produced cytokines [interleukin (IL)-6, IL-12, IFNgamma, tumor necrosis factor (TNF) receptor 1, and TNF receptor 2] to explain local tumor growth, anorexia, and carcass weight loss in a well-defined model with experimental cachexia. Indomethacin was provided in the drinking water to explore interactions between host and tumor-derived prostaglandins and proinflammatory cytokines for tumor growth. Wild-type tumor-bearing mice developed cachexia because of rapid tumor growth, which were both attenuated in IL-6 gene knockouts. Similar findings were observed after provision of anti-IL-6 to wild-type tumor-bearing mice. Alterations in food intake were not directly related to systemic IL-6 but rather secondarily to IL-6-dependent tumor growth. The absence of host-derived IL-12, IFN-gamma, or the TNF receptor 1 or receptor 2 gene did not attenuate tumor growth or improve subsequent cac...