ABSTRACT
OBJECTIVE To investigate the improvement effects and mechanism of imperatorin on cachexia model mice. METHODS Fifteen male C57BL/6J mice were randomly divided into blank control group， model group and imperatorin group， with 5 mice in each group. Except for blank control group， the remaining mice were inoculated with LLC cell suspension subcutaneously on the dorsal surface， and the drug was administered by gavage daily from the 7th day of inoculation. The imperatorin group was gavaged with imperatorin suspension （0.5% sodium carboxymethylcellulose solution as solvent） at 60 mg/kg； blank control group and model group were given an equal volume of 0.5% sodium carboxymethylcellulose solution， for 13 d of continuous administration. During the administration period， food intake and body mass of mice were recorded daily and regularly， tumor long and short diameters were measured every two days， and tumor volume was calculated. The skeletal muscle mass and tumor mass of each group were weighed and the tumor-free body weight was calculated； the pathological changes of skeletal muscle were observed and the cross-sectional area of skeletal muscle fibers was calculated； the phosphorylation levels of signal transduction and activator of transcription 3 （STAT3） （measured as p-STAT3/STAT3 ratio）， muscle atrophy box F gene （MAFbx）， myostatin （Myog）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase3 protein and mRNA expression were all detected. RESULTS Compared with blank control group， body mass and skeletal muscle mass of model group were decreased significantly （P＜0.05）， and reduced food intake， loose arrangement of skeletal muscle， large cell space were observed； the cross-sectional area of skeletal muscle fiber was significantly reduced， while p-STAT3/STAT3 ratio， protein and mRNA expressions of MAFbx， Bax and Caspase3 were somo_amour@163.com increased significantly （P＜0.05）. The protein and mRNA expressions of Myog and Bcl-2 were significantly reduced （P＜ 0.05）. Compared with model group， body weight， tumor-free weight and skeletal muscle weight were increased significantly in imperatorin group （P＜0.05）； food intake increased， while the expressions of tumor weight and volume were decreased significantly （P＜0.05）； the expressions of above proteins and genes were improved significantly （P＜0.05）. CONCLUSIONS Imperatorin can improve the tumor cachexia state， the mechanism of which may be related to the regulation of ubiquitin-proteasome pathway and anti-apoptosis.
ABSTRACT
Growth differentiation factor 15(GDF15) is a member of transforming growth factor β superfamily. Animal studies find that GDF15, bounding with centrally expressed receptors, reduces body weight by inhibiting food intake and by enhancing energy metabolism. In addition, GDF15 is also involved in the effects of tumor cachexia and platinum-based chemotherapy on body weight. GDF15 and its receptor could be potential targets for the treatment of such diseases.
ABSTRACT
ObjectiveTo explore the mechanism of Liu Junzitang in preventing and treating muscle atrophy in mice with lung cancer cachexia based on the signal transducer and activator of transcription 3（STAT3）/ubiquitin proteasome pathway in vivo. MethodForty C57BL/6 mice aged six weeks were randomly divided into a blank group， a model group， a Liu Junzitang group， an inhibitor group （stattic group），and a Liu Junzitang + inhibitor group （combination group）， with eight mice in each group. The cachectic muscle atrophy model was induced by subcutaneous inoculation of Lewis lung cancer cell line under the right anterior armpit in mice except those in the blank group. On the 8th day after subcutaneous inoculation， the mice in the corresponding groups received Liu Junzitang （9.56 g·kg-1·d-1） by gavage and intraperitoneal injection of stattic ［25 mg·kg-1·（2 d）-1］. After three weeks of drug intervention， the body weight and gastrocnemius muscle weight were recorded. Hematoxylin-eosin （HE） staining was used to observe the pathological changes and cross-sectional area of gastrocnemius muscle fibers in mice. Western blot was used to detect the expression of phosphorylated-STAT3 （p-STAT3）， STAT3， muscle atrophy F-box （MAFbx）， and muscle RING finger protein 1 （MuRF1） in the gastrocnemius muscle. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of STAT3， MAFbx， and MuRF1 in the gastrocnemius muscle. ResultCompared with the blank group， the model group showed lightened body and the gastrocnemius muscle， reduced cross-sectional area of gastrocnemius muscle fibers， and increased protein expression of p-STAT3， STAT3， MAFbx， and MuRF1 and mRNA expression of STAT3， MuRF1， and MAFbx in the gastrocnemius muscle （P<0.05）. Compared with the model group， the Liu Junzitang group showed increased body weight， gastrocnemius muscle weight， and cross-sectional area of gastrocnemius muscle fibers （P<0.05）， and decreased protein expression of p-STAT3， STAT3， MuRF1， MAFbx， and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle （P<0.05）. Compared with the model group， the inhibitor group showed increased body weight and cross-sectional area of gastrocnemius muscle fibers （P<0.05）， and reduced protein expression of p-STAT3， STAT3， MuRF1， MAFbx， and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle （P<0.05）. Compared with the model group， the combination group showed increased body weight and gastrocnemius muscle weight （P<0.05），and decreased protein expression of p-STAT3， STAT3， MuRF1， and mRNA expression of STAT3 and MAFbx in the gastrocnemius muscle （P<0.05）. Compared with the Liu Junzitang group， the stattic group and the combination group showed reduced expression of p-STAT3 protein in the gastrocnemius muscle （P<0.05）. ConclusionLiu Junzitang can prevent and treat muscle atrophy in mice with lung cancer cachexia， and its mechanism may be associated with the protein and mRNA expression related to the STAT3-mediated ubiquitin proteasome pathway.
ABSTRACT
Objective:The incidence rate of cancer cachexia is high in late stage of cancer， which is characterized by skeletal muscle atrophy and rapid reduction of adipose tissue and systemic inflammation. Cachexia is highly related to a variety of tumors， and causes a large proportion of cancer deaths. Cancer cachexia can lead to serious complications in patients with cancer， then， the quality of life of patients decreases， the psychological state becomes negative， and the state of illness is further worsened. At present， there is no effective intervention means to completely reverse cachexia. The combined use of multiple targets and effective components of traditional Chinese medicine（TCM）， as well as the treatment based on syndrome differentiation and the theory of TCM play an important role in the prevention and treatment of cancer cachexia. Therefore， exploring the pathogenesis of cancer cachexia and prevention and treatment with TCM is helpful for basic study and clinical application. Method:In this paper， cancer cachexia and TCM in China national knowledge infrastructure （CNKI） and Public Medline （PubMed） databases were retrieved， and 98 Chinese and English literatures were included through summarization to elaborate the pathogenesis of cancer cachexia and the prevention and treatment of TCM. Result:Emphasis was given to the important role of inflammatory reaction， skeletal muscle atrophy， energy metabolism abnormality and multiple signal joint regulation in occurrence of cancer cachexia， and the unique advantages and significant role of TCM in treatment of cancer cachexia under different treatment principles. Conclusion:Inflammatory reaction， skeletal muscle atrophy， abnormal energy metabolism make the pathogenesis of cancer cachexia complex and diverse. TCM prescriptions， Chinese herbal medicine and their effective ingredients have the natural advantages of targeting multiple pathways， controlling multiple signal pathways and inhibiting various inflammatory factors in the prevention and treatment of cancer cachexia， and are safe and effective in improving diet， prolonging the survival period of patients and keeping weight.
ABSTRACT
Food and eating are of great significance to humans, as we are the only creatures that establish relationships and sustain a social network through food and eating. Recent studies revealed that patients with advanced cancer and their family members often experience complicated eating-related distress due to tumors themselves, side effects of cancer treatments, and negative impacts of cancer cachexia. Therefore, we suggested the importance of the integration of palliative, supportive, and nutritional care to alleviate eating-related distress among patients and family members, and the significance of the development of tools to measure their distress in supportive and palliative care settings. No care strategies for eating-related distress experienced by patients and family members have been established, and the development of an interdisciplinary psychosocial approach and integrative care is required. As such, we are planning to start a nutritional support and cancer cachexia clinic in the National Cancer Center, and disseminate a newly developed care program across Japan.
ABSTRACT
Objective:To investigate the clinical features of preoperative gastric cancer cachexia patients, with the focus on changes of abdominal fat distribution and serum inflammatory factors.Methods:128 gastric cancer patients admitted to General Surgery Department of Zhongshan Hospital, Fudan University from January 2018 to December 2018 were included. Relevant clinical information was collected, including age, gender, height, weight, hematological test results and blood lipid profiles (including free fatty acids ,FFA). Concurrent serum IL-6 and TNF-α levels were examined using enzyme-linked immunosorbent assay. Areas of subcutaneous and visceral fat were both measured at umbilical level on CT. Data mentioned above were compared between gastric cancer patients with cachexia and pre-cachexia.Results:The 128 patients were divided into stable pre-cachexia group (97 patients) and cachexia group (31 patients). Compared with pre-cachexia group, patients in the cachexia group showed significant decline in BMIs (23.4±0.3 vs 21.9±0.6, t=2.359, P=0.019), apparent elevation in serum IL-6 levels [(3.73±0.32) ng/L vs(5.26±0.77) ng/L, t=2.214, P=0.036], significant decrease in lymphocyte counts [(1.67±0.05)×10 9/L vs (1.42±0.12)×10 9/L, t=2.251, P=0.026], as well as predominant decrease in total protein levels, [(64.9 ± 0.8) g/L vs (61.5±1.1) g/L, t=2.208, P=0.029], total cholesterol levels [(4.09±0.09) mmol/L vs (3.74±0.15) mmol/L, t=2.393, P=0.046] and pre-albumin levels [(0.22±0.01) g/L vs (0.19±0.01) g/L, t=1.987, P=0.049]. Additionally, there was a noticeable decrease in subcutaneous fat area [(151.6±8.73) cm 2vs (112.4±15.9) cm 2, t=2.192, P=0.042]. The other markers displayed no remarkable differences. Conclusion:Based on our investigation, it's highly suspected that IL-6 plays a more important role than TNF-α in the fat loss of gastric cancer cachexia patients, and these patients have increased lipid catabolism predominated by subcutaneous fat loss.
ABSTRACT
Background: Ghrelin plays a role in mechanisms related to cancer progression – including cell proliferation, invasion and migration, and resistance to apoptosis in the cell lines from several cancers. We investigated the role of ghrelin levels in cancer cachexia-anorexia in patients with locally advanced nonsmall-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT). Materials and Methods: This study involved 84 NSCLC patients who had received concomitant CRT. Blood ghrelin levels were compared before and 3 months after CRT. Meanwhile, changes in body weight of the patients were also investigated with changes in ghrelin levels before and after CRT. Results: Ghrelin levels were significantly decreased in line with changes in patients' weights in patients receiving CRT (P < 0.001). Serum albumin levels and inflammatory-nutritional index were significantly decreased after radiotherapy (RT) (3.01 ± 0.40 g/dL, 0.38 ± 0.20) when compared with its baseline levels (3.40 ± 0.55 g/dL,P < 0.001; 0.86 ± 0.71,P < 0.001, respectively). Serum C-reactive protein levels were significantly increased after CRT (7.49 ± 6.53 mg/L) when compared with its baseline levels (9.54 ± 3.80 mg/L,P = 0.038). After RT, ghrelin levels in patients were positively correlated with body mass index (r = 0.830,P < 0.001) and albumin (r = 0.758,P < 0.001). Conclusion: Ghrelin may play a role in the pathogenesis of weight loss in NSCLC patients. Ghrelin seems to be implicated in cancer-related weight loss. Ghrelin, cancer, and RT all together have a role in tumor-related anorexia-cachexia in patients with NSCLC. Results of this study need further evaluation as regards to its potential role as an adjuvant diagnostic or prognostic marker
ABSTRACT
Objective: The aim of this study is to elaborate on the nutritional intervention in a multimodal intervention (the NEXTAC-ONE program) for the elderly with advanced cancer and to evaluate its tolerability Methods: We prospectively recruited patients aged ≥70 years scheduled to receive first-line chemotherapy for advanced pancreatic or non-small-cell lung cancer. Three nutritional intervention were planned in 8-week study period. The nutritional counseling consists of standard nutritional advice, evaluation and support for nutrition impact symptom, and evaluation and support for eating-related distress and food environment problems. We also provide the oral nutritional supplements rich in Branched Chain Amino Acids (BCAA). Results: 29 patients (96%) of a total of 30 study registrants participated in all three nutrition interventions. Median proportion of days in which patients recorded a nutritional diary was 90%. Median consumption of supplements was 99 %. There was no adverse event associated with nutritional intervention. Conclusions: Our nutritional intervention program showed an excellent compliance in the elderly with advanced cancer patients, and our data indicated a potential protective effect on nutritional deterioration.
ABSTRACT
The objective of this study is to find the association between Ophiocephalus striatus extract supplementation and carnosine dipeptidase-1 plasma level in patient with cancer cachexia. This study was an open label study in which all subject knew the purpose of this study and understood the intervention they will get. The design for this study was one group pretest and posttest with inclusion and exclusion criteria to choose the ideal subject for this study. Descriptive statistics analysis used for demographic data and Wilcoxon test used to test numeric variable in study ®treatment groups before and after treatment. Subjects were treated with vipAlbuminsupplementation which contains 5000 mg Ophiocephalus striatus extract in 2 weeks period. The result from this study shows raised in Carnosine Dipeptidase-1 plasma level before and after treatment with Ophiocephalus striatus extract (p=0.007).
ABSTRACT
Objective To study the role of CFZ in the amelioration of hepatic function in cancer cachexia and its associated mechanism.Methods Forty BALB/c mice were selected.BALB/c mice were divided into 4 groups randomly,including a healthy control group (HC),a CFZ prevention group (CP),a CFZ treatment group (CT) and a cancer cachexia group (CC).Cancer cachexia model was induced by injecting murine colon 26 adencarcinoma cells into male BALB/c mice intraperitoneally.Following administration of CFZ intraperitoneally twice a week to CP and CT groups on the days 5 and 12 after tumor cells injection,respectively,all mice were acrificed on day 19.hepatic function was detected by automatic biochemistry analyzer,The concentration of inflammatory cytokines and CRP were detected by ELISA.The mRNA and protein expression of IκBα and p65 were detected by real-time PCR and western blotting.Results Compared with HC group,CP group and CT group,the albumin in CC group was significantly decreased,and the concentration of glutamate transaminase,total bilirubin,direct bilirubin and triglyceride were significantly increased,(221.67±12.38)U/L、(315.53±13.60)U/L、(1.65±0.32)mmol/L、(0.88±0.21) mmol/L、(4.98±0.32)mmol/L respectively.Liver biochemical test of CP group [(108.27±16.55)U/L、(180.45±15.28)U/L、(1.15±0.27) mmol/L、(0.58±0.12) mmol/L、(2.93±0.18) mml/L) and CT group [(148.56± 18.16)U/L、(247.18±21.64)U/L、(1.34±0.19) mmol/L、(0.69±0.16) mml/L、(3.75±0.28) mmol/L] was improved after CFZ treatment,and CP group was better than that of CT group.The concentrations of TNFa,IL-1,IL-6 and CRP in CC group [(156±9.56)ng/L、(762±9.46)ng/L、(962±9.12) ng/L、(772±10.04 ng/L)] were significantly higher than those in HC group[(16.42±5.63ng/L、174±9.61 ng/L、206±8.27 ng/L、397±10.2 ng/L)],CP group[(71.25± 4.41 ng/L、398±9.72 ng/L、398±9.72 ng/L、483±9.71 ng/L)] and CT group [(113±8.01 ng/L、506±8.74 ng/L、703± 7.76ng/L、651±11.31 ng/L)].The expression of IκBα in HC group,CP group and CT group were higher than that in CC group,and the difference was statistically significant.The expression of IκBαwas was more obvious in CP group than that in CT group.Compared with HC group,the expression of p65 in CP group,CT group and CC group was significantly increased,respectively,and the difference was statistically significant.The expression of p65 in CP group was lower than that in CT group(P=0.000).Conclusion CFZ ameliorates hepatic function in cancer cachexia mice,which may be related to the inhibition of NF-κB resulting in liver function improvement,the inhibition of tumor growth and the consumption of skeletal muscle.
ABSTRACT
Objective: To study the changes of mitochondria function and dynamics in colon cancer-cachexia mice and the effects of Shenqi Fuzheng Injection on these changes. Methods: A total of 40 female BLAB/c nu mice were randomly divided into control group, model group, low dose and high does of Shenqi Fuzheng Injection group, ten mice in every group. Except the control group, the mice of other groups were intraperitoneal injected with the Lovo cell line to establish the model of abdominal metastasis of colon cancer, then induced cancer cachexia. Marasmus and weight change were monitored the status of cancer cachexia in all groups. Shenqi Fuzheng Injection groups received intraperitoneal injection with 1.5 mL (2 times dose) and 3 mL (4 times dose) of drugs for every three days, seven consecutive times. After 21 days treatment, the mitochondrial related protein PGC-1, 4HNE and VDAC1 in the skeletal muscle were measured. The levels of adenosine triphosphate (ATP) and malondialdehyde (MDA) in the skeletal were detected. Results: Compared to the control group, the mice in the model group and Shenqi Fuzheng group suffered from cancer cachexia. Compared with the control group, the level of ATP in the skeletal muscle was lower in model group; The protein expression level of PGC-1 and 4HNE were remarkably increased (P 0.05); The level of MDA was significantly increased (P 0.05); The level of MDA was lower (P < 0.05). Conclusion: Shenqi Fuzheng Injection can significantly improve the status of colon cancer cachexia in mice, which may be related to the improvement of the mitochondrial function and the relieving of the mitochondrial oxidative damage.
ABSTRACT
Objective: To study the effect of Baoyuan Jiedu decoction on serum interleukin-6 (IL-6) content, expression of muscle atrophy F-box 1(Atrogin-1), muscle ring finger-1 (MuRF-1), uncoupling proteins-2 (UCP-2), uncoupling proteins-3 (UCP-3) in Apcmin/+ mice, in order to explore the mechanism in improving muscle atrophy in cancer cachexia model. Method: The 14-week-old Apcmin/+ cachexia mice model was randomly divided into model group, Baoyuan Jiedu decoction group (23 g·kg-1) and megestrol group (0.024 g·kg-1). C57BL/6J mice were normal group, with 10 mice in each group, and given continuous intragastric administration for 12 weeks. The quality of gastrocnemius muscle and the transverse diameter of muscle fibers were measured. The content of IL-6 in serum of Apcmin/+ cachexia mice was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Atrogin-1, MuRF-1, UCP-2, UCP-3 mRNA and protein in gastrocnemius muscle were detected by Western blot and quantitative real-time fluorescence polymerase chain reaction (Real-time PCR). Result: Compared with the normal group, the weight of gastrocnemius muscle and the transverse diameter of fibers in the model group decreased significantly (PPPPConclusion: Reduction of the concentration of IL-6 in serum and the down-regulation of the expressions of Atrogin-1, MuRF-1, UCP-2 and UCP-3 genes may be the possible mechanism of Baoyuan Jiedu decoction in alleviating muscle atrophy in Apcmin/+ cachexia mice model.
ABSTRACT
Brown adipose tissue (BAT) plays a fundamental role in maintaining body temperature by producing heat. BAT that had been know to exist only in mammals and the human neonate has received great attention for the treatment of obesity and diabetes due to its important function in energy metabolism, ever since it is recently reported that human adults have functional BAT. In addition, beige adipocytes, brown adipocytes in white adipose tissue (WAT), have also been shown to take part in whole body metabolism. Multiple lines of evidence demonstrated that transplantation or activation of BAT or/and beige adipocytes reversed obesity and improved insulin sensitivity. Furthermore, many genes involved in BATactivation and/or the recruitment of beige cells have been found, thereby providing new promising strategies for future clinical application of BAT activation to treat obesity and metabolic diseases. This review focuses on recent advances of BAT function in the metabolic aspect and the relationship between BAT and cancer cachexia, a pathological process accompanied with decreased body weight and increased energy expenditure in cancer patients. The underlying possible mechanisms to reduce BAT mass and its activity in the elderly are also discussed.
Subject(s)
Animals , Humans , Adipose Tissue, Brown , Metabolism , Aging , Metabolism , Cachexia , Metabolism , Pathology , Disease Models, Animal , Energy Metabolism , Metabolic Syndrome , Metabolism , Neoplasms , Metabolism , Pathology , Obesity , Metabolism , ThermogenesisABSTRACT
There is a lack of recognition regarding the negative impact of cancer cachexia on advanced cancer patients and their family members. Management of cancer cachexia should address not only patients’ physical problems, but also psychosocial burdens of both patients and their family members. Eating-related distress (ERD) is one of the most representative psychosocial burdens experienced during cancer. Summary points of palliative care and nutritional support for ERD experienced by patients and their family members are described as below. 1) Management strategies should address ERD experienced by patients and their family members. 2) If multimodal treatments reduce the negative impact of cachexia, ERD placed on patients and their family members might be alleviated. 3) The main causes of ERD experienced by patients and their family members are a lack of knowledge about cachexia, unsuccessful attempts to increase body weight, expected occurrence of the patient’s death, and conflicts over food between them. 4) Supportive, communicative, and educational interventions would alleviate ERD of patients and their family members. 5) Palliative care and nutritional support for ERD experienced by patients and their family members needs to be tailored to the severity of the patient’s cachexia, especially in cases of refractory cachexia. Since ERD can change during cancer, palliative care and nutritional support need to be tailored to each advanced cancer patient and their family.
ABSTRACT
Objectives: We developed the multimodal program Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC program). The aim of our study is to show algorithm of the home-based resistance training prescription and its compliance. Methods: We recruited 30 patients aged≥70 years scheduled to receive first-line chemotherapy for advanced pancreatic or non-small-cell lung cancer. Three educational sessions were planned in 8-week study period. Our resistance training consists of 3 or 5 of following 5 exercises components: (1) sit-to-stand, (2) calf raise, (3) knee extension, (4) knee raise, (5) side leg raise. Physiotherapist chose optimal prescription according to the modified Borg-scale. We assessed patient compliance, and safety. Results: Median proportion of days in which patients performed full or modified exercise program was 91%. Adverse events possibly related to the NEXTAC program were observed in 5 patients and included muscle pain (grade 1 in 2 patients), arthralgia (grade 1 in one patient), dyspnea on exertion (grade 1 in one patient), and plantar aponeurositis (grade 1 in one patient). Patient physical function and physical activity were maintained during the study period. Conclusion: Our resistance training showed excellent compliance and safety in elderly patients with newly diagnosed pancreatic and non-small-cell lung cancer receiving concurrent chemotherapy. Although this study was not designed to show the efficacy of the resistance training, our data indicate a potential protective effect on physical function and physical activity.
ABSTRACT
Aim To investigate the therapeutic effect of total saponins of Panax japonicus(SPJ)on cancer cach-exia in mice with colon adenocarcinoma. Methods BALB/c mice were subcutaneously inoculated with mu-rine colon adenocarcinoma CT26 cells to induce ca-chexia. The model animals were randomly divided into three groups: model group, SPJ low dose group and high dose group. Gavage started on the 4th day after inoculation, and the dosage regimen was as follows:the normal and model groups were given 10 mL·kg-1 saline, qd ×27; the low dose and high dose groups were treated with 20 and 60 mg·kg-1SPJ respective-ly, qd ×27. After treatment, the effects of SPJ on body weight, tibialis anterior muscle, gastrocnemius muscle,spleen and epididymal fat changes of cachexia mice were observed. HE and Western blot were used to measure the changes of cross section of gastrocnemius muscle fibers and the expression of NF-κB,PAX7 and MuRF1 protein level in the gastrocnemius and tibialis anterior muscle. Results Compared with model group, the administration of SPJ could effectively re-duce the weight loss (P <0.05), increase muscle mass (P<0.05) and decrease muscle tissue degrada-tion in cachexia mice. Meanwhile,SPJ significantly re-duced the levels of IL-1β and TNF-α in serum (P <0.05) and decreased the expression of NF-κB. Con-clusion SPJ can improve cancer cachexia in mice in a dose-dependent manner. The potential mechanism may be associated with the inhibition of NF-κB mediated in-flammatory factor expression.
ABSTRACT
[Objective]To investigate the effect of pantoprazole on skeletal muscle wasting in cancer cachexia and the possible mechanism.[Methods]24 male BALB/c mice were randomly divided into control group(NN),cancer cachexia group(CC),pantrop?razole treatment group(PPI). The mice in CC and PPI were inoculated subcutaneously with mouse colon adenocarcinoma C26 cells to establish a model of cancer cachexia. The mice in PPI group were gavaged with 75 mg/kg pantoprazole dissolving in physiological saline,while those in NN and CC group were gavaged with 0.1 mL/10 g physiological saline. The mice were killed 12d after treatment. The weight of gastrocnemius and tumour and the size of tumour were measured. The morphological change of skeletal muscle were evalu?ated by the method of stain with hematoxylin and eosin(H&E). The levels of IL-6 and TNF-αin serum were tested by ELISA. qRT-PCR was used to assess the expression of mRNA of Myod1 and myf5 in skeletal muscle. The protein expressions of MuRF1,MAFBx, Myod1 and myf5 were measured by Western blot.[Results]Compared with CC group ,pantoprazole can increase the weight of mice and gastrocnemius(39.8% and 24.2%,respectively),cross section area(25.4%),levels of mRNA and protein of Myod1 and myf5(P<0.05),while the levels of IL-6 and TNF-αdecreased(30.7%and 18.9%,respectively),as well as the levels of protein ex?pression of MuRF1 and MAFBx(P < 0.05).[Conclusion]Pantoprazole can attenuate the wasting of skeletal muscle,the potential mechanism may be related to the inhibition of inflammatory factors and UPS ,and up-regulation of Myod1 and myf5.
ABSTRACT
Objective:To explore the clinical value of PUFA in the treatment of cancer cachexia,meta-analysis and systematic evaluation of literature was applied.Methods:According to the inclusion criteria,PubMed/MEDLINE,EMBASE and the Cochrane Central Register of Controlled TriMs for randomized controlled trims that compared PUFA treatments with placebo or no treatment in cancer cachexia were searched.Outcomes of interest were effects on weight,appetite,the level of CRP and IL-6,the composition of lean body mass and the quality of life.Results:Finally,16 articles were included in the analysis,which reported appetite (6 papers),C-reactive protein (9 papers),IL-6 (5 papers),lean tissue weight (7 papers) and quality of life assessment (7 papers),respectively.Conclusion:PUFAs for the treatment of cancer cachexia plays an irreplaceable role.The body weight,appetite,inflammation index and quality of life can be significantly improved,and the patients can tolerated the addition of PUFA during the treatment.
ABSTRACT
<p>Cancer cachexia is a multifactorial syndrome defined by ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support. Nutritional treatment is a component of nutritional support, as well as symptom palliation and nutritional counseling. Nutritional treatment, exercise, and pharmacological agents are essential for treating cancer cachexia. In our studies at palliative care units, 76% and 73% of advanced cancer patients and bereaved families, respectively, required nutritional support, and nutritional support was also found to have beneficial effects on selected groups of advanced cancer patients. Our studies also indicated that as chronic inflammation is the underlying cause of cancer cachexia the plasma C-reactive protein (CRP) level might be useful as a prognostic marker/biomarker of advanced cancer. It was suggested that nutritional support based on the mechanism responsible for cancer cachexia is useful during the treatment of cancer cachexia although the evidence for this is not robust, and the CRP level is suggested to be a clinically significant index of the response to such treatment.</p>
ABSTRACT
Cancer cachexia is a state of highly wasting in the terminal stages of cancer, which is characterized by the depletion of adipose tissue, muscle wasting and body weight loss.Loss of fat depots is more prominent than muscle wasting and often precedes.The enhancement of lipolysis, free fatty acids oxidation and white adipose tissue browning, the reduction of lipogenesis, lipid deposition and adipogenesisare important factors causing fat loss.Tumor necrosis factor α, interleukin-6 and zinc α2-glycoprotein are mediators involved in the process of depletion of adipose tissue, thus the drugs targetingthese mediators show a good promise for the treatment of cancer cachexia.The attention paid to the mechanism of depletion of adipose tissue contributes to the development of new therapeutic methods and drugs.