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2.
Int J Mol Sci ; 22(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361081

RESUMO

Cancer cachexia is a common deleterious paraneoplastic syndrome that represents an area of unmet clinical need, partly due to its poorly understood aetiology and complex multifactorial nature. We have interrogated multiple genetically defined larval Drosophila models of tumourigenesis against key features of human cancer cachexia. Our results indicate that cachectic tissue wasting is dependent on the genetic characteristics of the tumour and demonstrate that host malnutrition or tumour burden are not sufficient to drive wasting. We show that JAK/STAT and TNF-α/Egr signalling are elevated in cachectic muscle and promote tissue wasting. Furthermore, we introduce a dual driver system that allows independent genetic manipulation of tumour and host skeletal muscle. Overall, we present a novel Drosophila larval paradigm to study tumour/host tissue crosstalk in vivo, which may contribute to future research in cancer cachexia and impact the design of therapeutic approaches for this pathology.


Assuntos
Caquexia/patologia , Carcinogênese/patologia , Modelos Animais de Doenças , Larva/crescimento & desenvolvimento , Neoplasias/complicações , Animais , Caquexia/etiologia , Caquexia/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Drosophila , Perfilação da Expressão Gênica , Humanos , Janus Quinases/genética , Janus Quinases/metabolismo , Larva/genética , Larva/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
3.
Gan To Kagaku Ryoho ; 48(8): 987-991, 2021 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-34404062

RESUMO

Cancer cachexia is defined as a multifactorial syndrome that causes anorexia and an ongoing loss of skeletal muscle mass (with or without loss of fat mass). When patients got cachexia, the effectiveness and tolerance for anti-cancer therapy is reduced, leading to their poor prognosis. Although known as such disease, there had been no effective cure for cancer cachexia. Ghrelin is a peptide hormone that promotes appetite and improve cachexia. However, there is a limitation as a drug because its half-life is short and must be intravenous injected. Anamorelin is a first novel drug, an orally active, non- peptidic ghrelin mimetic and growth hormone secretagogue approved in Japan in January 2021. Like ghrelin, anamorelin also increases the appetite and lean body mass of patients with cancer cachexia. On the other hand, in clinical trials, there was no statistical significance for increasing the 6-minute walk test distance and recovering non-dominant hand grip strength. As for the functional recovery, a new program has been developed for non-pharmacotherapy with nutritional and exercise interventions. These 2 kinds of interventions will become effective anti-cachexia therapy. Research is also underway to produce anti-cachexia drugs other than anamorelin. Somes are already in their clinical trials. Anti-cachexia therapy will be a new option for treating advanced cancer.


Assuntos
Caquexia , Neoplasias , Anorexia/tratamento farmacológico , Anorexia/etiologia , Apetite , Caquexia/tratamento farmacológico , Caquexia/etiologia , Força da Mão , Humanos , Neoplasias/complicações
4.
Molecules ; 26(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34443492

RESUMO

Muscle wasting and cachexia are prominent comorbidities in cancer. Treatment with polyphenolic compounds may partly revert muscle wasting. We hypothesized that treatment with curcumin or resveratrol in cancer cachectic mice may improve muscle phenotype and total body weight through attenuation of several proteolytic and signaling mechanisms in limb muscles. In gastrocnemius and soleus muscles of cancer cachectic mice (LP07 adenocarcinoma cells, N = 10/group): (1) LC-induced cachexia, (2) LC-cachexia+curcumin, and (3) LC-cachexia + resveratrol, muscle structure and damage (including blood troponin I), sirtuin-1, proteolytic markers, and signaling pathways (NF-κB and FoxO3) were explored (immunohistochemistry and immunoblotting). Compared to nontreated cachectic mice, in LC-cachexia + curcumin and LC-cachexia + resveratrol groups, body and muscle weights (gastrocnemius), limb muscle strength, muscle damage, and myofiber cross-sectional area improved, and in both muscles, sirtuin-1 increased, while proteolysis (troponin I), proteolytic markers, and signaling pathways were attenuated. Curcumin and resveratrol elicited beneficial effects on fast- and slow-twitch limb muscle phenotypes in cachectic mice through sirtuin-1 activation, attenuation of atrophy signaling pathways, and proteolysis in cancer cachectic mice. These findings have future therapeutic implications as these natural compounds, separately or in combination, may be used in clinical settings of muscle mass loss and dysfunction including cancer cachexia.


Assuntos
Caquexia/etiologia , Caquexia/fisiopatologia , Curcumina/farmacologia , Músculos/patologia , Músculos/fisiopatologia , Neoplasias/complicações , Proteólise , Resveratrol/farmacologia , Animais , Biomarcadores/metabolismo , Linhagem Celular , Feminino , Camundongos Endogâmicos BALB C , Proteínas Musculares/metabolismo , Músculos/efeitos dos fármacos , Atrofia Muscular/metabolismo , Fenótipo , Proteólise/efeitos dos fármacos , Transdução de Sinais , Sirtuína 1/metabolismo
5.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34445197

RESUMO

The term "cachexia" is derived from the Greek words kakos (bad) and hexis (habit). Cachexia is a malnutrition associated with chronic diseases such as cancer, chronic heart failure, chronic renal failure, and autoimmune diseases, and is characterized by decreased skeletal muscle mass. Cancer cachexia is quite common in patients with advanced cancer. Weight loss is also a characteristic symptom of cancer cachexia, along with decreased skeletal muscle mass. As nutritional supplementation alone cannot improve cachexia, cytokines and tumor-derived substances have been attracting attention as its relevant factors. Cancer cachexia can be also associated with reduced chemotherapeutic effects, increased side effects and treatment interruptions, and even poorer survival. In 2011, a consensus definition of cachexia has been proposed, and the number of relevant research reports has increased significantly. However, the pathogenesis of cachexia is not fully understood, and there are currently few regulatory-approved standard treatments for cachexia. The main reason for this is that multiple etiologies are involved in the development of cachexia. In this review, we will outline the current status of cachexia, the mechanisms of which have been elucidated in recent years, especially from the perspective of advanced cancer.


Assuntos
Caquexia/etiologia , Neoplasias/complicações , Anilidas/uso terapêutico , Animais , Caquexia/diagnóstico , Caquexia/fisiopatologia , Caquexia/terapia , Suplementos Nutricionais , Gerenciamento Clínico , Humanos , Hidrazinas/uso terapêutico , Neoplasias/fisiopatologia , Oligopeptídeos/uso terapêutico
6.
Oncoimmunology ; 10(1): 1950411, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290909

RESUMO

Although previous studies suggest that cancer cachexia is a poor prognostic factor for immune checkpoint inhibitor monotherapy, the impact of cancer cachexia on chemoimmunotherapy is unclear. We investigated the impact of cancer cachexia on the therapeutic outcomes of chemoimmunotherapy for non-small cell lung cancer (NSCLC). We retrospectively analyzed patients' medical records with NSCLC who received chemoimmunotherapy in 12 institutions in Japan between January and November 2019. We defined cancer cachexia as weight loss exceeding 5% of the total body weight or a body mass index of < 20 kg/m2 and weight loss of more than 2% of the total body weight within 6 months before chemoimmunotherapy initiation, with laboratory results exceeding reference values. This study enrolled 235 patients with NSCLC, among whom 196 were eligible for analysis, and 50 (25.5%) met the criteria for cachexia diagnosis. Patients with cancer cachexia had a significantly higher frequency of a programmed death-ligand 1 (PD-L1) expression of ≥ 50% (48%, p = .01) and shorter progression-free survival (PFS; log-rank test: p = .04) than patients without cachexia. There was no significant difference in overall survival (OS) between the cachexia and no-cachexia groups (log-rank test: p = .14). In the PD-L1 ≥ 50% population, there was no significant difference in PFS and OS (log-rank test: p = .19 and p = .79, respectively) between patients with NSCLC in the cachexia or no-cachexia groups. Cancer cachexia might be a poor prognostic factor in patients with NSCLC receiving chemoimmunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Caquexia/etiologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Humanos , Japão/epidemiologia , Neoplasias Pulmonares/complicações , Intervalo Livre de Progressão , Estudos Retrospectivos
7.
Nutrients ; 13(6)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207529

RESUMO

Nutritional status in oncological patients may differ according to several modifiable and non-modifiable factors. Knowledge of the epidemiology of malnutrition/cachexia/sarcopenia may help to manage these complications early in the course of treatment, potentially impacting patient quality of life, treatment intensity, and disease outcome. Therefore, this narrative review aimed to critically evaluate the current evidence on the combined impact of tumor- and treatment-related factors on nutritional status and to draw some practical conclusions to support the multidisciplinary management of malnutrition in cancer patients. A comprehensive literature search was performed from January 2010 to December 2020 using different combinations of pertinent keywords and a critical evaluation of retrieved literature papers was conducted. The results show that the prevalence of weight loss and associated symptoms is quite heterogeneous and needs to be assessed with recognized criteria, thus allowing a clear classification and standardization of therapeutic interventions. There is a large range of variability influenced by age and social factors, comorbidities, and setting of cures (community-dwelling versus hospitalized patients). Tumor subsite is one of the major determinants of malnutrition, with pancreatic, esophageal, and other gastroenteric cancers, head and neck, and lung cancers having the highest prevalence. The advanced stage is also linked to a higher risk of developing malnutrition, as an expression of the relationship between tumor burden, inflammatory status, reduced caloric intake, and malabsorption. Finally, treatment type influences the risk of nutritional issues, both for locoregional approaches (surgery and radiotherapy) and for systemic treatment. Interestingly, personalized approaches based on the selection of the most predictive malnutrition definitions for postoperative complications according to cancer type and knowledge of specific nutritional problems associated with some new agents may positively impact disease course. Sharing common knowledge between oncologists and nutritionists may help to better address and treat malnutrition in this population.


Assuntos
Caquexia/etiologia , Desnutrição/etiologia , Neoplasias/complicações , Estado Nutricional , Sarcopenia/etiologia , Caquexia/epidemiologia , Humanos , Desnutrição/epidemiologia , Oncologia/estatística & dados numéricos , Neoplasias/fisiopatologia , Avaliação Nutricional , Prevalência , Fatores de Risco , Sarcopenia/epidemiologia
8.
FASEB J ; 35(8): e21826, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34320244

RESUMO

In pancreatic cancer, autocrine insulin-like growth factor-1 (IGF-1) and paracrine insulin stimulate both IGF-1 receptor (IGF1R) and insulin receptor (IR) to increase tumor growth and glycolysis. In pancreatic cancer patients, cancer-induced glycolysis increases hepatic gluconeogenesis, skeletal muscle proteolysis, and fat lipolysis and, thereby, causes cancer cachexia. As a protein coexisting with IGF1R and IR, caveolin-1 (cav-1) may be involved in pancreatic cancer-induced cachexia. We undertook the present study to test this hypothesis. Out of wild-type MiaPaCa2 and AsPC1 human pancreatic cancer cell lines, we created their stable sub-lines whose cav-1 expression was diminished with RNA interference or increased with transgene expression. When these cells were studied in vitro, we found that cav-1 regulated IGF1R/IR expression and activation and also regulated cellular glycolysis. We transplanted the different types of MiaPaCa2 cells in growing athymic mice for 8 weeks, using intact athymic mice as tumor-free controls. We found that cav-1 levels in tumor grafts were correlated with expression levels of the enzymes that regulated hepatic gluconeogenesis, skeletal muscle proteolysis, and fat lipolysis in the respective tissues. When the tumors had original or increased cav-1, their carriers' body weight gain was less than the tumor-free reference. When cav-1 was diminished in tumors, the tumor carriers' body weight gain was not changed significantly, compared to the tumor-free reference. In conclusion, cav-1 in pancreatic cancer cells stimulated IGF1R/IR and glycolysis in the cancer cells and triggered cachectic states in the tumor carrier.


Assuntos
Caquexia/etiologia , Caveolina 1/metabolismo , Glicólise/fisiologia , Neoplasias Pancreáticas/metabolismo , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/metabolismo , Animais , Caveolina 1/genética , Linhagem Celular Tumoral , Deleção de Genes , Regulação da Expressão Gênica/fisiologia , Humanos , Camundongos , Camundongos Nus , Neoplasias Experimentais/metabolismo , Receptor IGF Tipo 1/genética , Receptor de Insulina/genética
9.
Cell Death Dis ; 12(7): 652, 2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34175899

RESUMO

Cancer cachexia is a multifactorial metabolic syndrome that causes up to 20% of cancer-related deaths. Muscle atrophy, the hallmark of cancer cachexia, strongly impairs the quality of life of cancer patients; however, the underlying pathological process is still poorly understood. Investigation of the disease pathogenesis largely relies on cachectic mouse models. In our study, the transcriptome of the cachectic gastrocnemius muscle in the C26 xenograft model was integrated and compared with that of 5 more different datasets. The bioinformatic analysis revealed pivotal gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the disease, and the key genes were validated. Construction of the protein-protein interaction network and the comparison of pathways enriched in cancer cachexia with 5 other muscle atrophy models revealed Ddit4 (DNA damage-inducible transcript 4), as a key protein in cancer cachexia. The higher expression of Ddit4 in cachectic muscle was further validated in animal models and cachectic cancer patients. Further study revealed that p38 induced the expression of Ddit4, which in turn inhibited the mTOR pathway in atrophic cells.


Assuntos
Adenocarcinoma/complicações , Caquexia/genética , Neoplasias do Colo/complicações , Perfilação da Expressão Gênica , Músculo Esquelético/metabolismo , Fatores de Transcrição/genética , Transcriptoma , Animais , Caquexia/etiologia , Caquexia/metabolismo , Caquexia/patologia , Linhagem Celular Tumoral , Bases de Dados Genéticas , Modelos Animais de Doenças , Redes Reguladoras de Genes , Humanos , Masculino , Camundongos Endogâmicos BALB C , Músculo Esquelético/patologia , Fosforilação , Mapas de Interação de Proteínas , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
Zentralbl Chir ; 146(3): 277-282, 2021 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-34154007

RESUMO

Cachexia is defined as a multifactorial syndrome characterised by involuntary progressive weight loss due to a decrease in skeletal muscle mass, with or without a reduction in adipose tissue. The breakdown of muscle tissue is known as sarcopenia. This is clinically defined as loss of muscle mass and/or muscle strength, with loss of muscle strength being more important than muscle mass. Cachexia is responsible for the death of at least 20% of all cancer patients. The incidence in these patients varies, depending on the type of disease, between 80% for patients with gastric and pancreatic cancer, 50% for patients with lung, colon and prostate cancer, and about 40% for patients with breast cancer or leukemia. It is often difficult to distinguish between tumour-associated cachexia and cachexia caused by side effects and complications of oncological therapy. The main clinical feature of cachexia is involuntary weight loss, but this does not always manifest itself clinically, making it much more difficult to identify patients at risk. Not only the long-term outcome of the patient is influenced by cachexia and sarcopenia. Immediate postoperative complication rates (morbidity) are also increased and have profound effects on the burden of disease and the suffering of patients after surgical treatment. Cachexia, sarcopenia and myosteatosis are therefore highly relevant parameters for everyday clinical practice, which have a significant influence on the postoperative outcome of the patient. Several tools have been developed to aid the identification of patients with nutritional risk, i.e. involuntary weight loss, reduced muscle strength and physical condition. Such measures should be a part of our daily clinical routine to ensure the identification of patients with the highest postoperative risk. Novel preconditioning treatment may be beneficial to certain patient groups to reduce postoperative morbidity.


Assuntos
Neoplasias , Sarcopenia , Caquexia/diagnóstico , Caquexia/etiologia , Caquexia/patologia , Humanos , Masculino , Músculo Esquelético/patologia , Neoplasias/patologia , Sarcopenia/diagnóstico , Sarcopenia/patologia , Síndrome
11.
BMJ Case Rep ; 14(5)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059533

RESUMO

A 65-year-old patient with background of alcohol excess and previous gunshot wounds was admitted with significant weight loss, leg cramps, dizziness and lethargy for the last 3 months. He was diagnosed with type 2 diabetes mellitus in July 2020 and was started on Metformin and Gliclazide by his in July; he was later commenced on alogliptin and empaglaflozin by diabetes specialist nurse in early August. He also had generalised muscle wasting, dorsal guttering in both hands and was cachectic when he presented to hospital. His haemoglobin A1c (HbA1c) was 124 mmol/mol in July 2020 and was 63 mmol/mol in September 2020. The patient had negative autoimmune and TB screen. CT abdomen/pelvis and CT lumbosacral spine that showed mild diverticular disease and bilateral L5 spondylolysis with L5-S1 spondylotic changes. Electrophysiological studies confirmed sensory motor peripheral neuropathy. Patient was diagnosed with diabetic neuropathic cachexia secondary to poorly controlled diabetes and was commenced on 30 units two times per day of NovoMix 30 insulin; this was adjusted to 24 units two times per day in endocrine clinic 3 months later, after gaining 10 kg in weight. Good glycaemic control is key to the management of such cases and, therefore, we recommend early referral to diabetes specialist input for consideration of insulin therapy.


Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Ferimentos por Arma de Fogo , Idoso , Caquexia/etiologia , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/complicações , Hemoglobina A Glicada , Humanos , Masculino
12.
J Clin Invest ; 131(11)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34060483

RESUMO

Skeletal muscle wasting is commonly associated with chronic kidney disease (CKD), resulting in increased morbidity and mortality. However, the link between kidney and muscle function remains poorly understood. Here, we took a complementary interorgan approach to investigate skeletal muscle wasting in CKD. We identified increased production and elevated blood levels of soluble pro-cachectic factors, including activin A, directly linking experimental and human CKD to skeletal muscle wasting programs. Single-cell sequencing data identified the expression of activin A in specific kidney cell populations of fibroblasts and cells of the juxtaglomerular apparatus. We propose that persistent and increased kidney production of pro-cachectic factors, combined with a lack of kidney clearance, facilitates a vicious kidney/muscle signaling cycle, leading to exacerbated blood accumulation and, thereby, skeletal muscle wasting. Systemic pharmacological blockade of activin A using soluble activin receptor type IIB ligand trap as well as muscle-specific adeno-associated virus-mediated downregulation of its receptor ACVR2A/B prevented muscle wasting in different mouse models of experimental CKD, suggesting that activin A is a key factor in CKD-induced cachexia. In summary, we uncovered a crosstalk between kidney and muscle and propose modulation of activin signaling as a potential therapeutic strategy for skeletal muscle wasting in CKD.


Assuntos
Caquexia/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Insuficiência Renal Crônica/metabolismo , Síndrome de Emaciação/metabolismo , Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/metabolismo , Ativinas/genética , Ativinas/metabolismo , Animais , Caquexia/etiologia , Caquexia/genética , Modelos Animais de Doenças , Células HEK293 , Humanos , Camundongos , Camundongos Knockout , Atrofia Muscular/etiologia , Atrofia Muscular/genética , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/genética , Síndrome de Emaciação/etiologia , Síndrome de Emaciação/genética
13.
Nutrition ; 90: 111271, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34004417

RESUMO

OBJECTIVES: Previous attempts to classify cancer cachexia (CC) have demonstrated limitations regarding stages and diagnostic criteria. This study aims to develop and validate a new staging system for CC in patients with incurable cancer. METHODS: This is an analysis of a database from a prospective cohort study of 1325 patients with advanced cancer referred for palliative care between 2016 and 2020. The cohort was randomly divided into two groups: Development (882 patients) and validation (443 patients) sets. A hierarchical cluster analysis was performed to distinguish different stages of CC in the development set. Next, the optimal cutoff points and ideal combinations of the most important factors associated with the CC groups (clusters) were ascertained. Finally, the relationship between the CC stages determined using the new system and body composition, quality of life, and overall survival was verified with the validation set. RESULTS: The new system classified CC into three stages: Precachexia (10.8%), cachexia (57.8%), and refractory cachexia (31.4%), based on a combination of percentage weight loss in the past 6 mo (<15 or ≥15), body mass index (<21.0, 21.0-26.4, >26.4 kg/m2), and mid-upper-arm muscle area (≥38.0/≥35.5 or <38.0/<35.5 cm2 in men/women, respectively). The new staging system enabled a clear classification of patients into three CC groups according to the outcomes analyzed. Outcomes of patients with refractory cachexia were significantly worse than those in the other groups. CONCLUSIONS: This study presents a useful, valid system for CC staging in the clinical setting, and is also capable of predicting outcomes, including quality of life and overall survival.


Assuntos
Caquexia , Neoplasias , Caquexia/diagnóstico , Caquexia/etiologia , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias/complicações , Neoplasias/patologia , Estudos Prospectivos , Qualidade de Vida
14.
BMC Cancer ; 21(1): 563, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001060

RESUMO

BACKGROUND: Cancer cachexia worsens the treatment outcomes of patients with small-cell lung cancer (SCLC). However, no reliable biomarker of cancer cachexia is yet known. METHODS: We retrospectively evaluated male SCLC patients who received induction chemotherapy or concurrent chemoradiotherapy. The cachexia index (CXI) was calculated as skeletal muscle index × serum albumin level (g/dL)/neutrophil-to-lymphocyte ratio. The CXI cutoff according to tumor stage was determined based on a time-dependent receiver operating characteristic curve, and all patients were divided into low- and high-CXI groups. RESULTS: Of 267 patients, 83 and 24 patients with limited-stage disease (LD) and 123 and 37 patients with extensive-stage disease (ED) were assigned to the high- and low-CXI groups, respectively. Only one of 24 patients (4.2%) with LD in the low-CXI group achieved a complete response (CR), whereas 30 of 83 patients (36.1%) with LD in the high-CXI group achieved CRs (p = 0.004). More low-CXI patients required early discontinuation of treatment because of treatment-related toxicity compared to the high-CXI patients (37.5% vs. 16.9%, respectively, p = 0.030, for LD patients; 27.0% vs. 11.4%, respectively, p = 0.019, for ED patients). The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the low-CXI group than the high-CXI group (6.3 vs. 11.1 months and 7.5 vs. 20.6 months, respectively, both p <  0.001 for LD patients; 2.9 vs. 6.3 months and 5.8 vs. 12.8 months, respectively, both p <  0.001, for ED patients). On multivariate analysis, low-CXI status was an independent poor prognostic factor for both PFS and OS regardless of the tumor stage. CONCLUSION: A low CXI was associated with treatment intolerance, poor treatment response rate, and poor prognosis in SCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Caquexia/diagnóstico , Quimiorradioterapia/efeitos adversos , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Caquexia/sangue , Caquexia/etiologia , Quimiorradioterapia/métodos , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Contagem de Linfócitos , Linfócitos , Masculino , Estadiamento de Neoplasias , Neutrófilos , Músculos Peitorais/diagnóstico por imagem , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Albumina Sérica Humana/análise , Índice de Gravidade de Doença , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Tomografia Computadorizada por Raios X
15.
Nutrients ; 13(3)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33808957

RESUMO

Cancer cachexia subsequently shifts to refractory cachexia, however, it is not easy to properly differentiate them in clinical settings. Patients considered refractory cachexia may include cachectic patients with starvation. This study aimed to identify these cachectic patients and to evaluate the effect of nutritional intervention for them. Study subjects were terminal cancer patients admitted for palliative care and were judged refractory cachexia in the last five years. We retrospectively examined to find useful indices for identifying such cachectic patients and for evaluating the effect of nutritional intervention. Out of 223 patients in refractory cachexia, 26 were diagnosed cachexia with starvation after symptom management. Comparing before and one week after this management, Palliative Performance Scale (PPS) and transthyretin significantly improved (p < 0.0001, p = 0.0002, respectively) Then, we started nutritional intervention for these cachectic patients and divided into effective group (n = 17) and non-effective group (n = 9) using the criteria for cachexia. Comparing between the two groups, PPS significantly improved2 weeks after intervention in effective group (p = 0.006). Survival time was significantly longer in effective group (p = 0.008). PPS and transthyretin were useful for differential diagnosis of cachexia and refractory cachexia. PPS was useful for evaluating nutritional intervention for cachectic patients. Appropriate nutritional intervention improved survival.


Assuntos
Caquexia/diagnóstico , Neoplasias/complicações , Apoio Nutricional/métodos , Assistência Terminal/métodos , Adulto , Caquexia/dietoterapia , Caquexia/etiologia , Caquexia/mortalidade , Diagnóstico Diferencial , Humanos , Neoplasias/dietoterapia , Neoplasias/mortalidade , Cuidados Paliativos/métodos , Nutrição Parenteral , Falha de Tratamento
16.
Int J Clin Oncol ; 26(7): 1293-1303, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33791917

RESUMO

BACKGROUND: Elderly pancreatic cancer (PC) patients are often considered vulnerable to treatment and standard treatment strategy for this subpopulation is uncertain. Cachexia and sarcopenia are reported to be associated with reduced physical performance, reduced anti-tumor response, increased chemotherapy toxicity, and poor prognosis in several malignancies. The aim of this study was to evaluate the impact of cachexia and sarcopenia on the clinical course of elderly PC patients receiving chemotherapy. METHODS: We retrospectively investigated consecutive elderly metastatic PC patients (≥ 75 years) treated with chemotherapy at our institution between January 2015 and April 2020. Skeletal muscle index was calculated at the third lumbar vertebra using pretreatment computed tomography. We evaluated time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), early treatment discontinuation, relative dose intensity (RDI), and severe adverse events (AEs). RESULTS: Among 80 patients included (gemcitabine plus nab-paclitaxel [GnP] 52; gemcitabine 21; S1 6; modified FOLFIRINOX 1), cachexia and sarcopenia were present in 48 (60%) and 61 (76%) patients, respectively. Cachexia was associated with older age, worse performance status, higher level of neutrophil to lymphocyte ratio, worse nutritional status, and shorter TTF and PFS. Furthermore, it was also associated with early treatment discontinuation, reduced RDI of nab-paclitaxel, and increased incidence of grade 4 neutropenia in patients receiving GnP. On the other hand, sarcopenia had less impact on the clinical course of elderly PC patients. CONCLUSIONS: In our experience, cachexia was considered an effective tool in the management of elderly PC patients receiving palliative chemotherapy.


Assuntos
Neoplasias Pancreáticas , Sarcopenia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Caquexia/tratamento farmacológico , Caquexia/etiologia , Humanos , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Retrospectivos , Sarcopenia/complicações
17.
Cochrane Database Syst Rev ; 3: CD010804, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33735441

RESUMO

BACKGROUND: Cancer cachexia is a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass, with or without a loss of fat mass, leading to progressive functional impairment. Physical exercise may attenuate cancer cachexia and its impact on patient function. This is the first update of an original Cochrane Review published in Issue 11, 2014, which found no studies to include. OBJECTIVES: To determine the effectiveness, acceptability and safety of exercise, compared with usual care, no treatment or active control, for cancer cachexia in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and eight other databases to March 2020. We searched for ongoing studies in trial registries, checked reference lists and contacted experts to seek relevant studies. SELECTION CRITERIA: We sought randomised controlled trials in adults with cancer cachexia, that compared a programme of exercise alone or in combination with another intervention, with usual care, no treatment or an active control group. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed titles and abstracts for relevance and extracted data on study design, participants, interventions and outcomes from potentially relevant articles. We used standard methodological procedures expected by Cochrane. Our primary outcome was lean body mass and secondary outcomes were adherence to exercise programme, adverse events, muscle strength and endurance, exercise capacity, fatigue and health-related quality of life. We assessed the certainty of evidence using GRADE and included two Summary of findings tables. MAIN RESULTS: We included four new studies in this update which overall randomised 178 adults with a mean age of 58 (standard deviation (SD) 8.2) years. Study sample size ranged from 20 to 60 participants and in three studies the proportion of men ranged from 52% to 82% (the fourth study was only available in abstract form). Three studies were from Europe: one in the UK and Norway; one in Belgium and one in Germany. The remaining study was in Canada. The types of primary cancer were head and neck (two studies), lung and pancreas (one study), and mixed (one study). We found two comparisons: exercise alone (strength-based exercise) compared to usual care (one study; 20 participants); and exercise (strength-based exercise/endurance exercise) as a component of a multimodal intervention (pharmacological, nutritional or educational (or a combination) interventions) compared with usual care (three studies, 158 participants). Studies had unclear and high risk of bias for most domains. Exercise plus usual care compared with usual care We found one study (20 participants). There was no clear evidence of a difference for lean body mass (8 weeks: MD 6.40 kg, 95% CI -2.30 to 15.10; very low-certainty evidence). For our secondary outcomes, all participants adhered to the exercise programme and no participant reported any adverse event during the study. There were no data for muscle strength and endurance, or maximal and submaximal exercise capacity. There was no clear evidence of a difference for either fatigue (4 to 20 scale, lower score was better) (8 weeks: MD -0.10, 95% CI -4.00 to 3.80; very low-certainty evidence) or health-related quality of life (0 to 104 scale, higher score was better) (8 weeks: MD 4.90, 95% CI -15.10 to 24.90; very low-certainty evidence). Multimodal intervention (exercise plus other interventions) plus usual care compared with usual care We found three studies but outcome data were only available for two studies. There was no clear evidence of a difference for lean body mass (6 weeks: MD 7.89 kg, 95% CI -9.57 to 25.35; 1 study, 44 participants; very low-certainty evidence; 12 weeks: MD -2.00, 95% CI -8.00 to 4.00; one study, 60 participants; very low-certainty evidence). For our secondary outcomes, there were no data reported on adherence to the exercise programme, endurance, or maximal exercise capacity. In one study (44 participants) there was no clear evidence of a difference for adverse events (patient episode report) (6 weeks: risk ratio (RR) 1.18, 95% CI 0.67 to 2.07; very low-certainty evidence). Another study assessed adverse events but reported no data and the third study did not assess this outcome. There was no clear evidence of a difference in muscle strength (6 weeks: MD 3.80 kg, 95% CI -2.87 to 10.47; 1 study, 44 participants; very low-certainty evidence; 12 weeks MD -5.00 kg, 95% CI -14.00 to 4.00; 1 study, 60 participants; very low-certainty evidence), submaximal exercise capacity (6 weeks: MD -16.10 m walked, 95% CI -76.53 to 44.33; 1 study, 44 participants; very low-certainty evidence; 12 weeks: MD -62.60 m walked, 95% CI -145.87 to 20.67; 1 study, 60 participants; very low-certainty evidence), fatigue (0 to 10 scale, lower score better) (6 weeks: MD 0.12, 95% CI -1.00 to 1.24; 1 study, 44 participants; very low-certainty evidence) or health-related quality of life (0 to 104 scale, higher score better) (12 weeks: MD -2.20, 95% CI -13.99 to 9.59; 1 study, 60 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: The previous review identified no studies. For this update, our conclusions have changed with the inclusion of four studies. However, we are uncertain of the effectiveness, acceptability and safety of exercise for adults with cancer cachexia. Further high-quality randomised controlled trials are still required to test exercise alone or as part of a multimodal intervention to improve people's well-being throughout all phases of cancer care. We assessed the certainty of the body of evidence as very low, downgraded due to serious study limitations, imprecision and indirectness. We have very little confidence in the results and the true effect is likely to be substantially different from these. The findings of at least three more studies (one awaiting classification and two ongoing) are expected in the next review update.


Assuntos
Caquexia/terapia , Exercício Físico , Neoplasias/complicações , Viés , Caquexia/etiologia , Terapia Combinada/métodos , Tolerância ao Exercício , Fadiga/etiologia , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Força Muscular , Neoplasias Pancreáticas/complicações , Cooperação do Paciente , Resistência Física , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Magreza
18.
Nutr Clin Pract ; 36(4): 793-807, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33666957

RESUMO

Cannabinoids have been used medicinally for thousands of years. Clinical trials support their use for treatment of chemotherapy-induced nausea and vomiting and HIV- and AIDS-related anorexia. Cancer anorexia cachexia syndrome (CACS) is a common debilitating condition and is associated with poor prognosis. The 2016 European Society for Parenteral and Enteral Nutrition clinical guidelines on nutrition in cancer patients concluded that "there are insufficient consistent clinical data to recommend cannabinoids to improve taste disorders or anorexia in cancer patients." The increased attention that cannabinoids have received in recent years warrants an updated evaluation of the literature on this topic, as practitioners are likely to encounter cancer patients interested in cannabinoid use. A systematic literature search was performed to assess the current body of evidence concerning cannabinoid use for the stimulation of appetite and oral intake by cancer patients. Over the past 20 years, 6 randomized controlled trials have evaluated the impact of cannabinoids on appetite-related outcomes in oncology patients in comparison with a control group or placebo. Based on this literature, cannabinoids do not appear to improve appetite, oral intake, weight, chemosensory function, or appetite-related quality of life. Limitations of the literature include small sample sizes, lack of adjustment for confounding variables, and difficulties conducting true placebo-controlled trials with a drug that may result in psychoactive side effects. Further exploration of the impact of cannabinoid use on CACS by using large, well-designed clinical trials is needed.


Assuntos
Canabinoides , Neoplasias , Anorexia/etiologia , Apetite , Caquexia/etiologia , Canabinoides/efeitos adversos , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Qualidade de Vida , Ganho de Peso
19.
J Biomed Sci ; 28(1): 15, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658022

RESUMO

Although rheumatoid arthritis affects 1% of the global population, the role of rheumatoid cachexia, which occurs in up to a third of patients, is relatively neglected as research focus, despite its significant contribution to decreased quality of life in patients. A better understanding of the cellular and molecular processes involved in rheumatoid cachexia, as well as its potential treatment, is dependent on elucidation of the intricate interactions of the cells involved, such as myoblasts, fibroblasts and macrophages. Persistent RA-associated inflammation results in a relative depletion of the capacity for regeneration and repair in the satellite cell niche. The repair that does proceed is suboptimal due to dysregulated communication from the other cellular role players in this multi-cellular environment. This includes the incomplete switch in macrophage phenotype resulting in a lingering pro-inflammatory state within the tissues, as well as fibroblast-associated dysregulation of the dynamic control of the extracellular matrix. Additional to this endogenous dysregulation, some treatment strategies for RA may exacerbate muscle wasting and no multi-cell investigation has been done in this context. This review summarizes the most recent literature characterising clinical RA cachexia and links these features to the roles of and complex communication between multiple cellular contributors in the muscle niche, highlighting the importance of a targeted approach to therapeutic intervention.


Assuntos
Artrite Reumatoide/complicações , Caquexia/fisiopatologia , Fibroblastos/metabolismo , Macrófagos/metabolismo , Músculo Esquelético/patologia , Mioblastos/metabolismo , Animais , Caquexia/etiologia , Humanos , Camundongos , Ratos
20.
Best Pract Res Clin Endocrinol Metab ; 35(3): 101508, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33648847

RESUMO

Cancer cachexia is a metabolic syndrome characterized by unintended weight loss and muscle wasting. It has a strong negative impact on survival. Its underlying mechanisms involve systemic inflammation and insulin resistance, which are known to be influenced by the gut microbiota. Preclinical studies support a role for the gut microbiota in cancer cachexia by demonstrating that cachectic mice display: 1) various gut microbiota composition changes; 2) increased gut permeability and translocation of pro-inflammatory microbial compounds; 3) muscle atrophy-related processes linked to gut microbiota properties; 4) positive effects of microbiota-modulating interventions. Data on the relationships between gut microbiota, insulin resistance, and hepatic/adipose tissue metabolism in cachexia models are lacking. Nevertheless, the available data and existing evidence for the impact of gut microbiota on metabolic aberrations in human obesity urge for exploration of its role in human cancer cachexia. We provide practical recommendations and discuss the challenges for such future clinical studies.


Assuntos
Microbioma Gastrointestinal , Resistência à Insulina , Microbiota , Neoplasias , Animais , Caquexia/etiologia , Humanos , Inflamação , Camundongos , Neoplasias/complicações
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