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Current Opinion in Supportive and... Sep 2023To explore the current evidence relating to the practical management of cancer cachexia in palliative care. (Review)
Review
PURPOSE OF REVIEW
To explore the current evidence relating to the practical management of cancer cachexia in palliative care.
RECENT FINDINGS
The authors found a growing evidence base including the publication of several expert guidelines since 2020. Guidelines identified the need for individualised nutritional and physical exercise support as the mainstay of cachexia management. Dietician and allied health professional referrals are recommended for the best patient outcomes. Limitations of nutritional support and exercise are acknowledged. Patient outcomes from multimodal anti-cachexia therapy are awaited at this time. Communication about the mechanisms of cachexia and nutritional counselling are identified as ways to reduce distress. Evidence supporting the use of pharmacological agents remains insufficient to make recommendations. Corticosteroids and progestins may be offered for symptom relief in refractory cachexia, taking into consideration well-documented side effects. Emphasis is placed on adequately managing nutritional impact symptoms. A specific role for palliative care clinicians and the use of existing palliative care guidelines in managing cancer cachexia were not identified.
SUMMARY
Current evidence recognises the inherently palliative nature of cancer cachexia management, and practical guidance correlates with the tenets of palliative care. Individualised approaches to support nutritional intake, physical exercise and alleviate symptoms that accelerate cachexia processes are currently recommended.
Topics: Humans; Palliative Care; Quality of Life; Cachexia; Nutritional Support; Neoplasms
PubMed: 37384429
DOI: 10.1097/SPC.0000000000000655 -
Expert Opinion on Pharmacotherapy Jun 2023Cachexia is a complex multi-factorial syndrome characterized by anorexia, inflammation, body, and skeletal muscle wasting. Early diagnosis and intervention via a... (Review)
Review
INTRODUCTION
Cachexia is a complex multi-factorial syndrome characterized by anorexia, inflammation, body, and skeletal muscle wasting. Early diagnosis and intervention via a multimodal approach combining nutritional counseling, exercise, and pharmacological agents is advisable. However, no effective treatment options are currently available in the clinical setting.
AREAS COVERED
The present work is a review of emerging treatment options for cancer cachexia, including mainly, but not only, pharmacological approaches. The main interest is on drugs currently investigated in clinical trials; however, promising pre-clinical options are presented as well. Data were collected using PubMed and ClinicalTrials.gov databases, including studies of the last 20 years and active clinical trials.
EXPERT OPINION
The lack of effective therapeutic approaches against cachexia results from several issues, among which a reduced number of studies focused on new drugs. Furthermore, the translation of pre-clinical results in the clinical practice is a hard mission, and it must be considered whether drugs target cachexia as a consequence of acting directly on the tumor. Indeed, dissecting antineoplastics from direct anti-cachexia effects is needed to elucidate the mechanisms of action of specific drugs. This is necessary for their inclusion into multimodal approaches, which nowadays are considered the best way to tackle cachexia.
Topics: Humans; Neoplasms; Cachexia; Exercise; Counseling
PubMed: 37132359
DOI: 10.1080/14656566.2023.2209316 -
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 -
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 -
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 Ethnopharmacology Oct 2019.Colorectal cancer (CRC) is now one the fourth cause of mortality and morbidity due to cancer throughout the globe. Cachexia is more prevalent in patients with this...
.Colorectal cancer (CRC) is now one the fourth cause of mortality and morbidity due to cancer throughout the globe. Cachexia is more prevalent in patients with this cancer and has a negative effect on response to chemotherapy and radiotherapy. Inflammatory cytokines such as TNF-α, IL-1β, and IL-6 could play a key role in cachexia. Moreover strong chemotherapy medications such as doxorubicin have complications such as toxicity and cachexia. Citrus unshiu Peel have been used as traditional herbal drugs for the treatment of cancer in traditional oriental medicine (TOM). Since its main components have anti-inflammatory effects, we evaluated the anti-cachexia activity in order to support the traditional usage of Citrus unshiu peel. Aim of the study; We aimed to assess the preventive or therapeutic effect of Citrus unshiu Peel Extract (CUPE) on cachexia by reducing of inflammatory cytokines in mice bearing C26 tumor. Also the contribution role of CUPE has evaluated on improvement of chemotherapy through reducing of inflammatory cytokines. Materials and Methods; The CUPE was prepared by Soxhlet extractor and quantitative and qualitative analysis of aqua extract was performed by high performance liquid chromatography (HPLC). C26 tumor bearing BALB/c male mice were immunized with different formulation of oral Prophylactic-therapeutic CUPE and/or intraperitoneal doxorubicin and then were monitored for weight gain, food intake and tumor size throughout the study. On the 32nd day after tumor injection, inflammatory cytokines levels, IL6, TNF-α and IL-1β were evaluated by Enzyme-linked Immunosorbent Assay (ELISA) and Malondialdehyde- Thiobarbituric acid (MDA) levels were measured by standard method. Results; Oral administration of CUPE in both prophylactic and therapeutic formulation to C26 adenocarcinoma bearing mice reduced the weight loss, tumor volume, and serum MDA levels compared with untreated tumor-bearing mice and Doxorubicin (Dox) groups. Also, the combination therapy of (CUPE + Dox) leads to reducing the levels of serum IL-6, TNF-α, IL-1β and tumor volume compared with untreated tumor-bearing mice and Dox groups. Serum MDA levels were considerably reduced by combination therapy of (CUPE + Dox) compared with Dox groups. Conclusions; These findings confirm the safety and efficacy of CUPE on C26 adenocarcinoma bearing mice as pure and adjuvant therapy, the results of which might be used in further human studies as a valuable natural anticancer agent alone or in combination with chemotherapy. Also the results showed that simultaneous application of CUPE and Dox leads to significant reduction of cachexia from the Dox chemotherapy.
Topics: Adenocarcinoma; Animals; Antibiotics, Antineoplastic; Cachexia; Cell Line; Citrus; Colonic Neoplasms; Cytokines; Doxorubicin; Male; Mice, Inbred BALB C; Plant Extracts; Tumor Burden
PubMed: 31054317
DOI: 10.1016/j.jep.2019.111929 -
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 -
European Journal of Pharmacology Sep 2017Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent...
Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent for treatment of this syndrome. We investigated the anti-cachexia effects of Z-505 hydrochloride (Z-505), a new oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, using a mouse model of cancer cachexia. We performed a calcium flux assay in Chinese hamster ovary (CHO-K1) cells stably expressing human GHSR1a to quantify the agonistic activity of Z-505. In Colon 26 tumor-bearing mice, Z-505 (300mg/kg, p.o., twice daily) was administered for 7 days to assess its anti-cachexia effects. Body weight and food intake were monitored during the period, and the skeletal muscle and epididymal fat weights were measured. Serum levels of insulin, insulin-like growth factor 1 (IGF-1), interleukin-6 (IL-6), and corticosterone were measured to confirm the mechanism of the anti-cachexia action of Z-505. Z-505 showed strong agonistic activity similar to that of human ghrelin, with a half maximal effective concentration (EC) value of 0.45nM. Z-505 treatment significantly increased food intake and inhibited the progression of weight loss. Z-505 also significantly attenuated muscle wasting and fat loss, and increased circulating levels of anabolic factors such as insulin and IGF-1, but not catabolic factors such as IL-6 and corticosterone. These findings suggest that Z-505 might be effective in the treatment of cachexia via the increased anabolic hormone levels stimulated by the activation of the ghrelin receptor, GHSR1a.
Topics: Adipose Tissue; Administration, Oral; Animals; BALB 3T3 Cells; Body Weight; CHO Cells; Cachexia; Cell Line, Tumor; Colonic Neoplasms; Cricetulus; Disease Models, Animal; Disease Progression; Eating; Ghrelin; Hormones; Humans; Male; Mice; Quinolines; Rats; Receptors, Ghrelin
PubMed: 28529141
DOI: 10.1016/j.ejphar.2017.05.036 -
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