-
American Society of Clinical Oncology... 2015Many important advances have occurred in the field of cancer cachexia over the past decade, including progress in understanding the mechanisms of the cancer... (Review)
Review
Many important advances have occurred in the field of cancer cachexia over the past decade, including progress in understanding the mechanisms of the cancer anorexia-cachexia syndrome (CACS) and the development of promising pharmacologic and supportive care interventions. However, no approved agents for cancer cachexia currently exist, emphasizing the unmet need for an effective pharmacologic therapy. This article reviews the key elements of CACS assessment in daily practice, the contribution of nutritional impact symptoms (NIS), the evidence for current pharmacologic options, and promising anticachexia agents in perclinical and clinical trials. It also proposes a model for multimodality therapy and highlights issues pertinent to CACS in patients with pancreatic, gastric, and esophageal cancer.
Topics: Anorexia; Cachexia; Humans; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 25993178
DOI: 10.14694/EdBook_AM.2015.35.e229 -
Antioxidants & Redox Signaling Feb 2023Cancer is frequently associated with the early appearance of cachexia, a multifactorial wasting syndrome. If not present at diagnosis, cachexia develops either as a... (Review)
Review
Cancer is frequently associated with the early appearance of cachexia, a multifactorial wasting syndrome. If not present at diagnosis, cachexia develops either as a result of tumor progression or as a side effect of anticancer treatments, especially of standard chemotherapy, eventually representing the direct cause of death in up to one-third of all cancer patients. Cachexia, within its multiorgan affection, is characterized by severe loss of muscle mass and function, representing the most relevant subject of preclinical and clinical investigation. The pathogenesis of muscle wasting in cancer- and chemotherapy-induced cachexia is complex, and encompasses heightened protein catabolism and reduced anabolism, disrupted mitochondria and energy metabolism, and even neuromuscular junction dismantling. The mechanisms underlying these alterations are still controversial, especially concerning the molecular drivers that could be targeted for anticachexia therapies. Inflammation and mitochondrial oxidative stress are among the principal candidates; the latter being extensively discussed in the present review. Several approaches have been tested to modulate the redox homeostasis in tumor hosts, and to counteract cancer- and chemotherapy-induced muscle wasting, from exercise training to distinct classes of direct or indirect antioxidants. We herein report the most relevant results obtained from both preclinical and clinical trials. Including the assessment and the treatment of altered redox balance in the clinical management of cancer patients is still a big challenge. The available evidence suggests that fortifying the antioxidant defenses by either pharmacological or nonpharmacological strategies will likely improve cachexia and eventually the outcome of a broad cancer patient population. 38, 352-370.
Topics: Humans; Cachexia; Muscle, Skeletal; Neoplasms; Muscular Atrophy; Mitochondria; Oxidative Stress; Antineoplastic Agents
PubMed: 36310444
DOI: 10.1089/ars.2022.0149 -
Oncology (Williston Park, N.Y.) Jan 2017Weight loss is distressing to cancer patients and caregivers. Anorexia/cachexia syndrome is characterized by lipolysis and the loss of lean body mass, and is not... (Review)
Review
Weight loss is distressing to cancer patients and caregivers. Anorexia/cachexia syndrome is characterized by lipolysis and the loss of lean body mass, and is not reversible by increasing caloric intake. The pathophysiology of cancer cachexia is complex and includes symptoms that impact caloric intake, as well as chronic inflammation, hypermetabolism, and hormonal alterations. Cancer patients require routine screening for cachexia and, ideally, interventions should be initiated in the early stages of weight loss. No guidelines exist for the treatment of cancer cachexia. Appetite stimulants, such as megestrol acetate and glucocorticoids, have been shown to increase appetite and weight; however, single pharmaceutical interventions alone for cachexia do not result in meaningful functional outcomes. In the future, clinicians should consider multimodality treatment that is personalized for each patient. These interventions would include nutritional counseling, assessing and treating symptoms that have an impact on caloric intake, and a rational combination of pharmacologic approaches directed at underlying pathophysiology. Use of an appetite stimulant could be considered for patients who exhibit decreased appetite. Treatment with an anti-inflammatory agent should be considered for patients with elevated C-reactive protein, and hormonal alterations resulting from anti-cachexia therapy should be thoughtfully addressed.
Topics: Appetite Stimulants; Cachexia; Energy Intake; Humans; Neoplasms; Nutritional Support; Practice Guidelines as Topic
PubMed: 28090619
DOI: No ID Found -
Clinical Cancer Research : An Official... Aug 2016Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively affects quality of life and portends a poor... (Review)
Review
Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively affects quality of life and portends a poor prognosis. Numerous molecular substrates and mechanisms underlie the dysregulation of skeletal muscle synthesis and degradation observed in cancer cachexia, including proinflammatory cytokines (TNFα, IL1, and IL6), and the NF-κB, IGF1/AKT/mTOR, and myostatin/activin-SMAD pathways. Recent preclinical and clinical studies have demonstrated that anti-cachexia drugs (such as MABp1 and soluble receptor antagonist of myostatin/activin) not only prevent muscle wasting but also may prolong overall survival. In this review, we focus on the significance of cachexia signaling in patients with cancer and highlight promising drugs targeting tumor cachexia in clinical development. Clin Cancer Res; 22(16); 3999-4004. ©2016 AACR.
Topics: Animals; Antineoplastic Agents; Biomarkers; Cachexia; Clinical Trials as Topic; Cytokines; Humans; Molecular Targeted Therapy; Muscle Development; Muscle, Skeletal; Muscular Atrophy; Neoplasms; Proteolysis; Signal Transduction; Translational Research, Biomedical
PubMed: 27340276
DOI: 10.1158/1078-0432.CCR-16-0495 -
Molecules (Basel, Switzerland) Jul 2022Medicinal and food homologous adlay ( L. var. Stapf) plays an important role in natural products promoting human health. We demonstrated the systematic actional... (Review)
Review
Medicinal and food homologous adlay ( L. var. Stapf) plays an important role in natural products promoting human health. We demonstrated the systematic actional mechanism of functional ingredients in adlay to promote human health, based on the PubMed, CNKI, Google, and ISI Web of Science databases from 1988 to 2022. Adlay and its extracts are rich in 30 ingredients with more than 20 health effects based on human and animal or cell cultures: they are anti-cancer, anti-inflammation, anti-obesity, liver protective, anti-virus, gastroprotective, cardiovascular protective, anti-hypertension, heart disease preventive, melanogenesis inhibiting, anti-allergy, endocrine regulating, anti-diabetes, anti-cachexia, osteoporosis preventive, analgesic, neuroprotecting, suitable for the treatment of gout arthritis, life extending, anti-fungi, and detoxifying effects. Function components with anti-oxidants are rich in adlay. These results support the notion that adlay seeds may be one of the best functional foods and further reveal the action mechanism of six major functional ingredients (oils, polysaccharides, phenols, phytosterols, coixol, and resistant starch) for combating diseases. This review paper not only reveals the action mechanisms of adding adlay to the diet to overcome 17 human diseases, but also provides a scientific basis for the development of functional foods and drugs for the treatment of human diseases.
Topics: Animals; Anti-Allergic Agents; Coix; Functional Food; Humans; Phenols; Plant Extracts
PubMed: 35956759
DOI: 10.3390/molecules27154808 -
Scientific Reports Jul 2018Persimmon (Diospyros kaki L.) leaves are commonly used in Asia as tea infusion and as an agent in traditional medicine. The present study aims to explore the antitumor...
Persimmon (Diospyros kaki L.) leaves are commonly used in Asia as tea infusion and as an agent in traditional medicine. The present study aims to explore the antitumor and immunomodulatory effects of total flavonoids extract from persimmon leaves (PLF) in H liver tumor-bearing mice. We found that the PLF showed significant inhibition on the liver tumor growth in mice with a tumor inhibition rate of up to 49.35%. In contrast to the severe side effects of cyclophosphamide (CTX), the PLF exhibited anti-cachexia effect and showed no alternation in the body weight and food intake in mice. Moreover, compared with the vehicle control and CTX group, the PLF significantly enhanced the thymus and spleen indices, level of serum interleukin-18 (IL-18), monocyte/macrophage phagocytosis, level of serum hemolysin, and activity of natural killer (NK) cells. This study demonstrated that the PLF could effectively inhibit liver tumor growth in vivo via enhancement of the immune function in mice, and it displayed the potential to be a safe and effective anticancer agent or functional immune-enhancing agent.
Topics: Animals; Antineoplastic Agents, Immunological; Antineoplastic Agents, Phytogenic; Carcinoma, Hepatocellular; Cell Line, Tumor; Cyclophosphamide; Diospyros; Disease Models, Animal; Drug Screening Assays, Antitumor; Female; Flavonoids; Humans; Killer Cells, Natural; Liver Neoplasms; Macrophages; Male; Mice; Phagocytosis; Plant Extracts; Plant Leaves
PubMed: 30002398
DOI: 10.1038/s41598-018-28440-8 -
International Journal of Cancer Nov 2011Loss of adipose tissue, primarily due to increased lipolysis but also to an impairment of adipogenesis, is a key feature of weight loss in cancer cachexia. Because of...
Loss of adipose tissue, primarily due to increased lipolysis but also to an impairment of adipogenesis, is a key feature of weight loss in cancer cachexia. Because of the myriad pathogenic signaling pathways essential for atrophy of adipose tissue, effective therapeutic agents for cachectic adipose loss are lacking and urgently needed. The authors evaluated the effects of YC-1 on adipogenesis of 3T3-L1 preadipocytes, TNF-α- and tumor-cell-induced lipolysis in 3T3-L1 adipocytes, and cachectic weight loss in colon-26 adenocarcinoma-bearing mice because YC-1 has been shown to possess versatile pharmacological actions, including anticancer activity. It was found that YC-1 promotes the differentiation of 3T3-L1 preadipocytes into adipocytes through activation of Akt and extracellular signal-regulated kinase (ERK) signaling pathways as well as activation of several adipogenic mediators, such as peroxisome proliferator-activated receptor γ (PPARγ), insulin receptor α (IRα), insulin receptor substrate-3 (IRS-3) and glucose transporter-4 (GLUT-4). In the in vitro lipolysis models, YC-1 attenuates TNF-α-induced lipolysis of adipocytes by antagonizing TNF-α-mediated activation of ERK and downregulation of perilipin (PLIN). It was also found that YC-1 inhibits colon-26 adenocarcinoma cell-induced lipolysis of 3T3-L1 adipocytes. Moreover, YC-1 effectively rescues cachectic weight loss in colon-26 adenocarcinoma-bearing mice by blocking lipolysis, involving insulin. Taken together the results show that YC-1 with its anticancer and anticachexia talents is highly worth developing as a novel agent for cancer therapy.
Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Antineoplastic Agents; Cachexia; Enzyme Activators; Female; Indazoles; Lipolysis; Mice; Mice, Inbred BALB C; Neoplasms; Signal Transduction; Tumor Necrosis Factor-alpha
PubMed: 21557215
DOI: 10.1002/ijc.26174 -
Journal of Ethnopharmacology Mar 2021Astragalus membranaceus (Fisch.) and Bunge and Paeonia japonica (Makino)Miyabe & H.Takeda have been traditionally used to improve the poor quality of life such as... (Comparative Study)
Comparative Study
ETHNOPHARMACOLOGICAL RELEVANCE
Astragalus membranaceus (Fisch.) and Bunge and Paeonia japonica (Makino)Miyabe & H.Takeda have been traditionally used to improve the poor quality of life such as weakness, lack of appetite, fatigue, and malaise which is considered with cachexia condition.
AIM OF THE STUDY
We investigated anti-cachectic effects of a herbal formula composed of Astragalus membranaceus and Paeonia japonica (APX) and the molecular mechanisms of APX in C26 cancer-induced cachexia mice and TNF-a-treated C2C12 myotubes. Additionally synergistic anti-cachectic effects of APX were compared to those of individual herbal extracts and megestrol acetate.
METHODS AND MATERIALS
The forty-two BALB/c mice were randomly divided into 6 groups: normal (nontreatment), control (C26 injection), AM (C26 injection with Astragalus membranaceus), PJ (C26 injection with Paeonia japonica), APX (C26 injection with combination of Astragalus membranaceus and Paeonia japonica and MA (C26 injection with megestrol acetate). All mice were orally administered DW (normal and control groups) or 100 mg/kg AM, PJ, APX or MA for 10 days. In the animal model, several tissues were weighed, and muscle tissue and blood were used to measure pro-inflammatory cytokines. C2C12 myotubes were exposed to 100 ng/mL TNF- α with or without 10 μg/mL of AM, PJ, APX or MA for 48 h. The cells were used to immunofluorescence staining and western blot analyses.
RESULTS
C26 injection induced notable body and muscle weight loss while APX administration significantly attenuated these alterations and the decrease of muscle weights and strength. APX also significantly attenuated the abnormal elevations in the concentration of three muscle atrophy-inducible cytokines; serum and muscle TNF-α,muscle TWEAK and IL-6 in C26 tumor-bearing mice. In the TNF-α-treated C2C12 myotube model, TNF-α treatment notably decreased MyH but activated atrophic proteins (MuRF and Fbx32) along with p38 and NFκB while these molecular alterations were significantly ameliorated by APX treatment. These pharmacological actions of APX were supported by the results of immunofluorescence staining to MyH expression and the translocation of NFκB into the nucleus in C2C12 myotubes.
CONCLUSIONS
Our data indicate the potential of an herbal formula, APX as an anti-cachexia agent; the effect of APX was superior to that of megestrol acetate overall especially for muscle atrophy. The underlying mechanisms of this herbal formula may involve the modulation of muscle atrophy-promoting molecules including p38, NFκB, TNF-α and TWEAK.
Topics: Animals; Astragalus propinquus; Cachexia; Cell Line, Tumor; Colonic Neoplasms; Cytokine TWEAK; Cytokines; Inflammation Mediators; Male; Mice; Mice, Inbred BALB C; Muscle, Skeletal; Muscular Atrophy; NF-kappa B; Paeonia; Plant Extracts; Signal Transduction; p38 Mitogen-Activated Protein Kinases
PubMed: 33068652
DOI: 10.1016/j.jep.2020.113470 -
Journal of Nutrigenetics and... 2013Plant phenolics can inhibit, retard or reverse carcinogenesis, and may thus help prevent or treat cancer. Oil palm phenolics (OPP) previously showed anti-tumour...
BACKGROUND/AIM
Plant phenolics can inhibit, retard or reverse carcinogenesis, and may thus help prevent or treat cancer. Oil palm phenolics (OPP) previously showed anti-tumour activities in vivo via a cytostatic mechanism at 1,500 ppm gallic acid equivalent. Here, we report other possible molecular mechanisms by which this extract attenuates cancer, especially those concerning the immune response.
METHODS
We subcutaneously injected J558 myeloma cells in BALB/c mice and supplemented OPP orally at 1,500 ppm gallic acid equivalent. We observed the physiology parameters of these animals and harvested their spleens and livers after 18 h, 1 week and 4 weeks for microarray gene expression analysis using Illumina MouseRef-8 BeadChips.
RESULTS
Time course microarray analysis on spleens after injecting J558 myeloma cells in mice revealed that the immune response of tumour-bearing mice supplemented with OPP was lower compared to controls, thus suggesting delayed inflammation in response to OPP. In livers, cholesterol biosynthesis genes were upregulated while inflammatory genes were downregulated through time, further suggesting attenuation of systemic inflammation and cachexia. These effects correlated with the delayed in vivo development of syngeneic tumours in mice given OPP.
CONCLUSIONS
This study suggests the possible utilisation of OPP as an anti-tumour and anti-cachexia agent.
Topics: Animals; Cachexia; Dietary Supplements; Gallic Acid; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Inflammation; Liver; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Oligonucleotide Array Sequence Analysis; Palm Oil; Phenol; Plant Oils; Spleen; Tissue Distribution
PubMed: 24642698
DOI: 10.1159/000357948