恶性肿瘤发生中重度营养不良的发生率非常高,中国肿瘤患者的中度和重度营养不良发生率为58％,营养不良明显影响肿瘤患者的临床结局,近25％的肿瘤患者直接死于营养不良.许多营养不良的肿瘤患者常常表现高静息态能量消耗和高分解代谢.引发这些变化的因素主要包括两个方面:①肿瘤负荷;②由肿瘤引起的相关因素,包括炎症、神经内分泌紊乱、放化疗、肠道微生态紊乱以及食欲下降和摄入减少等.这些因素交杂在一起并通过尚未完全阐明的复杂机制而激活不同组织器官系统的能量消耗增加、分解代谢增强和合成代谢降低等,从而引起肿瘤患者的营养不良,甚至恶液质.由于引起肿瘤患者营养不良的因素和机制是复杂多样的,因此,肿瘤患者营养治疗也应该是针对性的综合治疗,即在营养不良综合评估和诊断基础上,进行有效综合营养干预和阻断高代谢的药物干预等.本文就肿瘤患者高能耗代谢及其相关机制进行综述.

人体微生态,尤其肠道菌群是人体一个新的动态器官,菌群及其代谢物可直接作用于肠道或间接通过菌群-肠-器官轴作用全身组织器官而发挥着重要作用.人体微生态的主要生理作用包括:调节胃肠道运动和消化、肠道屏障,调节免疫稳态和炎症反应、物质代谢、细胞分化和周转,以及认知行为等.肿瘤放疗可引起人体菌群的明显改变,表现为菌群多样性和丰度的下降,这些菌群变化不仅与放疗有关,而且也与放射损伤、并发症和预后等密切相关.同时放射损伤存在性别差异,而这种差异与肠道菌群的性别差异有关.因此,维护和调节人体微生态平衡影响着肿瘤放疗、放射损伤和并发症的防治.应用微生态制剂(益生菌、益生元和后生元)和粪菌移植在减少辐射引起的组织器官损伤、提高放疗和减少并发症等方面产生明显的作用,作为抗肿瘤辅助治疗手段显示出良好的临床应用前景.因此,针对疾病特异性和个体化的益生菌制剂的优化组合及其应用将是未来重要的研究方向.

目的 探索一种功能食品(五神)的抗肿瘤作用,并探讨该功能食品在抗肿瘤治疗中的应用前景.方法 取对数生长期Lewis细胞(鼠源性肺腺癌细胞系)悬液200μl(1×107/ml)接种于小鼠右后肢背部皮下构建肺癌Lewis皮下移植瘤模型.将小鼠分为以下四组:标准饮食饲养的对照组和顺铂组,添加功能食品饲料饲养的功能食品组及功能食品顺铂组,每组8只小鼠,顺铂组及功能食品顺铂组隔天按4 mg/kg体重腹腔注射顺铂,对照组与功能食品组注射等量生理盐水.实验过程中每周测量小鼠体重及移植瘤体积,按V=ab2π/6(a为最大直径,b为最小直径)计算,实验终点对瘤体称重,检测小鼠血清白蛋白、后肢肌围等营养指标,通过流式细胞仪检测小鼠脾脏、血清和肿瘤组织中相关免疫细胞亚群,ELISA检测试剂盒检测IL-6+T细胞及IL-10+T细胞等相关细胞因子,通过免疫组织化学检测瘤组织中微血管形成情况.结果 与对照组相比,功能食品组小鼠白蛋白及后肢肌围明显升高,但移植瘤体积及质量差异无统计学意义;与顺铂组相比,功能食品顺铂组移植瘤体积及质量明显降低,荷瘤小鼠免疫效应细胞亚群CD3+、CD4+T细胞,CD3+、CD8+T细胞,NK细胞的比例明显增高且差异有统计学意义;CD8+IFN-γ+、CD8+Perforin+T细胞和IL-10+T细胞比例降低,脾脏中抑制性免疫细胞亚群MDSCs和Treg细胞及肿瘤组织中的Treg细胞降低,但差异均无统计学意义.各组IL-6及IL-10差异无统计学意义.结论 功能食品能够增强顺铂的抗肿瘤疗效,这可能与改善小鼠营养状况、调节免疫等作用有关.

食欲下降是肿瘤患者常见症状,癌性厌食/恶液质综合征在晚期肿瘤患者中发病率较高.肿瘤患者因营养摄入不足,会出现全血细胞减少、体重下降、脂肪组织和骨骼肌减少,导致患者免疫力降低,治疗耐受性下降,治疗机会减少,并发症增加,不利于抗肿瘤治疗措施的实施.准确评估癌性厌食的过程,无论对研究还是临床救治都极为重要,科学的食欲评价方法和技术不仅是营养工作者客观评价食欲的工具,也是进一步认识和预测营养不良的基础,对改善肿瘤患者营养不良具有积极意义.本共识根据国内外现有研究证据,对该领域的研究结果进行系统总结.从肿瘤、营养与食欲的关系出发,分析癌性厌食的发生发展机制,总结不同情况下肿瘤患者的食欲评价方法,并给出专家推荐意见.结合我国膳食现状和特点,从临床、营养、护理、中医的角度提出调节食欲的方法,科学规范癌性厌食管理策略,以便临床医师、临床营养专业人员、护士等医疗保健人员应用,更好地为肿瘤患者服务.

雷公藤红素是一种中草药活性成分,具有广泛的治疗特性及较高的药用价值,通常用于治疗自身免疫性疾病、代谢性疾病及肿瘤.雷公藤红素可以通过多种途径抑制肿瘤的发生、发展,尤其与肿瘤代谢密切相关,对肿瘤细胞的糖代谢、脂类代谢、氨基酸代谢及肿瘤微环境产生重要影响.雷公藤红素导致线粒体功能障碍以改变葡萄糖代谢途径,使肿瘤细胞供能不足;通过诱导肝内Sirt1的表达影响肿瘤宿主的脂类代谢;抑制吲哚胺2,3双加氧酶(IDO)表达和色氨酸分解代谢来抑制结直肠癌,与IDO的抑制剂D-1MT联用控制胰腺癌;在肿瘤微环境中,雷公藤红素可通过抑制NLRP3炎性小体及重塑免疫抑制治疗黑色素瘤.根据最新研究报道,肠道菌群的高度代谢可以提高雷公藤红素在体内的功效,影响肿瘤发展.本文从代谢的角度阐述雷公藤红素对肿瘤的主要作用及机制,为其药理作用的深入研究提供科学依据.

不同免疫细胞亚群的代谢特征有所不同,抗肿瘤免疫细胞主要以有氧酵解和谷氨酰胺分解代谢提供代谢的物质与能量,而促进肿瘤发生和进展的抑制性免疫细胞亚群可利用肿瘤细胞代谢产物通过脂肪酸代谢等途径获取能量及中间产物.乳酸作为糖酵解途径的重要产物,直接或间接地影响肿瘤生物学行为,参与肿瘤免疫微环境调控.乳酸代谢的关键酶乳酸脱氢酶(LDH)常在肿瘤组织中高表达,是肿瘤微环境中连接各种免疫细胞代谢的关键酶之一,可激活某些信号传导途径和调控免疫应答参与肿瘤发生、发展.LDH水平升高主要由于肿瘤糖酵解活性增加和肿瘤缺氧坏死引起,其为免疫抑制性微环境的重要驱动者,LDH水平在一定程度上反映并可用于肿瘤糖酵解活性和免疫代谢状态的评估.本文对LDH与T淋巴细胞、巨噬细胞、树突状细胞等免疫细胞的代谢相关研究进行综述,旨在探究其在恶性肿瘤预后评估、抗肿瘤治疗尤其是免疫治疗疗效预测及监测中的可能应用.

Objective To investigate the sensitivity of pancreatic cancer cells to mannose under various glucose concentrations and the mechanisms. Methods CCK-8 cell viability and proliferation kit was used to detect the proliferation of pancreatic cancer cells under different concentrations of glucose and mannose. Trypan blue staining was used to calculate the survival rate of mannose-cultured cells. Western blot was used to observe the expression of PMI enzyme. A subcutaneous xenograft tumor model was established to test the efficacy of ketogenic diet combined with mannose. Results With the decrease of glucose concentration, the concentration of mannose required for the significant inhibition of pancreatic cancer cell proliferation was also significantly reduced; mannose significantly induced the expression of PMI enzymes in high glucose culture, and the induction effect was weakened in low glucose. The ketogenic diet had an effect on lowering blood sugar and raising blood ketones, and the inhibitory effect on the xenograft combined with mannose was significant. Conclusion Low glucose concentration enhances the tumor inhibitory effect of mannose, and the combination of ketogenic diet and mannose could improve the antitumor effect.

恶性肠梗阻是由恶性肿瘤引起的小肠或大肠梗阻,常见于卵巢癌及胃肠道肿瘤患者.恶性肠梗阻是由于肿瘤压迫、肿瘤细胞浸润自主神经、副肿瘤综合征或药物因素导致的急性或慢性肠道梗阻,是晚期肿瘤患者常见的致死性并发症之一.本文综合国内外进展探讨恶性肠梗阻患者的代谢紊乱情况及其机制,得出以下提示:恶性肠梗阻不仅引起葡萄糖、蛋白质、脂肪酸等宏量营养素的代谢紊乱,还会引起微量营养素代谢异常等.造成代谢紊乱的机制主要有肠道功能紊乱,肠道局部甚至全身发生炎性反应,肠道菌群紊乱及缺乏有效的营养治疗等因素.恶性肠梗阻患者发生代谢紊乱可能加剧肠梗阻的发展,更与患者的预后显著相关.临床决策中医生应重视患者的代谢情况,认识到代谢紊乱对恶性肠梗阻患者预后的影响,积极纠正代谢紊乱,提高患者的预后及生活质量.

We used the Halomonas sp. S62 β-galactosidase to synthesize galactooligosaccharides from lactose, to explore galactooligosaccharides synthesis efficiency. To improve the yield of galactooligosaccharides, the reaction conditions were optimized, and the orthogonal test was carried out by the reaction temperature, p H, enzyme dosage and substrate concentration. The optimal reaction conditions were as follows: reaction temperature 40 ℃, p H 7. 0, enzyme dosage 50 U/m L, substrate concentration 300 g/L.The maximal yield of galactooligosaccharides was (41. 91±0. 27) ％ at 6 h and the lactose consumption rate was (82. 47±0. 38) ％.Within 4-8 h, the yield of galactooligosaccharides was above 40％ and the lactose consumption rate was over80％.The yield of galactooligosaccharides was maintained above 40％ within 4-8 h of the reaction. The consumption rate of lactose was all above 80％. The utilization rate of lactose was increased while the high production of galactooligosaccharides was achieved, which was beneficial to the reduction of production cost, laying the foundation for the industrial application of low-temperature S62 β-galactosidase.

Monocarboxylate transporters MCTs are important transmembrane transporters responsible for monocarboxylate metabolites such as pyruvate lactate ketone bodies.They promote nutrient absorption of these substances and maintain the metabolic balance of cells.The expression of MCT in tumors is significantly up-regulated which is closely related to glucose metabolism lipid metabolism energy metabolism and the formation of tumor microenvironment and plays an essential role in maintaining the high glycolytic state of tumor cells.In some tumors lactic acid is produced by glycolytic cells in the hypoxic region excreted into the tumor microenvironment by MCT4 and then taken up by peripheral oxidized cells expressing MCT1 finally enters the TCA cycle and becomes a fuel for respiration.Pyruvate is also effluxed out of tumor cells by MCT1 and MCT2 while pyruvate in the tumor microenvironment promotes lung metastasis of breast cancer.At the same time MCT promotes the formation of acidic tumor microenvironment which is not only conducive to the growth proliferation and metastasis of tumors but also causes the death of normal cells around the tumor.The immunosuppression of tumors is also related to this.A number of studies have proved that the high expression of MCT1 and MCT4 is positively correlated with tumor malignancy and prognosis.Inhibition of MCT expression influences tumor growth proliferation and metastasis which provides potential therapeutic targets for targeted therapy.Currently MCT inhibitors such as CHC AR-C155858 and AZD3965 are lack of selectivity for MCT subtypes but have shown good therapeutic effects.While developing new MCT inhibitors exploring strategies for joint application with traditional tumor therapies has a good clinical application prospect.

“Warburg效应”是肿瘤细胞重要的代谢特征之一,肿瘤细胞在氧气充足的条件下仍进行糖酵解,亦称“有氧糖酵解”.愈来愈多的研究表明肿瘤是一种代谢性疾病.因此探索肿瘤代谢变化及机制,以及靶向肿瘤代谢的肿瘤治疗成为近年来肿瘤研究的热点.目前基于肿瘤代谢的一些治疗方法(如生酮疗法、大剂量维生素C等)逐步引起基础研究和临床研究工作者的重视.最近有研究报导,甘露糖可以抑制肿瘤生长、增加阿霉素抗癌效果和延长荷瘤小鼠生存期.其主要作用机制是干扰葡萄糖代谢、促进肿瘤细胞凋亡以及增强化疗药物顺铂和阿霉素的抗肿瘤作用.此外,甘露糖还有调节免疫平衡等作用.甘露糖作为一种营养素,对人体健康无害,有望成为一种重要肿瘤代谢调节治疗的营养素,并且可与一线肿瘤治疗(化疗和放疗)配合来提高抗肿瘤治疗效果,具有重要的临床意义和应用前景.

Objective To test the effect of different glucose levels on the anti-tumor effect of metformin and explore its mechanism. Methods Cells cultured in the mediums with different glucose levels were treated with metformin for 24 hours. Then, we detected cell proliferation and ATP levels. A subcutaneous xenograft tumor model was established in nude mice in vivo. Nude mice were randomly divided into four groups: standard diet(SD) group, SD+metformin(Met) group, ketogenic diet(KD) group and KD+Met group. After 8 weeks of experimental intervention, tumor volume and weight and blood glucose level in nude mice were detected. Results Metformin did not inhibit the proliferation of pancreatic cancer cells when the glucose level was above 10mmol/L, but 10mmol/L metformin significantly inhibited the proliferation of pancreatic cancer cells in low glucose medium (≤5mmol/L). At the same time, the ATP level of each cell in low glucose medium was significantly decreased (P＜0.01). In vivo, blood glucose level was significantly decreased in KD group (P＜0.01), and KD significantly inhibited tumor growth (P＜0.01). Compared with KD group, KD+Met group could further inhibit the growth of the xenografts (P＜0.05). Conclusion Low glucose enhances the sensitivity of cancer to metformin and metformin exerts anti-tumor effect by reducing the body's ATP production.

生酮代谢疗法(KMT)是通过一种高脂、低碳水化合物和适当蛋白质的配方饮食来模拟了人体饥饿的状态,由脂肪代谢产生的酮体作为供给机体的主要能量,通过影响细胞代谢、信号和炎症等机制达到防治疾病的一种治疗方法,目前应用于神经系统疾病、葡萄糖代谢缺陷遗传病、代谢性疾病、肿瘤等治疗.

Abstract: TKTL-1 is a member of human TKT gene family, and the genes of the TKT family consist of TKT , TKTL-1 and TKTL-2. In human body, pentose phosphate pathway contains two pathways: oxidation pathway and non-oxidation pathway, TKT plays a key role in non-oxidative pathway. It catalyzes the conversion of ketose into aldose in the body. After a series of reactions, it continuously generates 5-phosphorylated ribose and NAPDH which are the raw materials of antioxidant response and biosynthesis. The current study suggests that there is a close relationship between TKTL-1 and the occurrence, development and metastasis of tumors. Some studies found that TKTL-1 has a different activity from other TKTs and shows high expression in many tumors, while the expressions of TKT and TKTL-2 in malignant tumors have no obvious regularity or just small changes. In this paper, we divide the role of TKTL-1 in malignant tumors into four aspects. First and foremost, TKTL-1 can provide raw materials for tumors, work in coordination with the reprogramming of cancer metabolism and provide a material basis for the proliferation and metastasis of malignant tumors. In addition, the high expression of TKTL-1 can promote the metastasis of tumor to peripheral lymph nodes. What’s more, TKTL-1 is closely related to the immunosuppression and drug resistance of the tumor: it produces lactic acid by glycolysis, inhibiting the immune monitoring of T cells and NK cells; and the inhibition of oxygen free radical production by lactic acid will reduce the antitumor effect of sorafenib and other drugs. At present, numerous studies have shown that TKTL-1 is a potential tumor marker which has great significance on the diagnosis and prognosis of tumors. In terms of treatment, studies have shown that the TKTL-1 inhibitors can inhibit tumor growth and metastasis, so TKTL-1 may be a potential biotherapeutic target. Co-treatment of TKTL-1 inhibitors with other metabolic modulation therapies may further enhance the anti-tumor efficacy of TKTL-1 .

目的 活性乳清蛋白(active whey protein)是采用低温专利萃取技术获得的牛乳中以乳清蛋白为主的产品,蛋白含量高达90%以上,具有改善营养状况和增强免疫力等多种生物学作用,是临床营养治疗中提供机体营养的重要组分之一.本研究构建胰腺癌荷瘤鼠模型,探讨活性乳清蛋白在胰腺癌营养治疗中的疗效.方法 构建胰腺癌panc-1细胞裸鼠皮下移植瘤模型,根据不同的营养干预方式随机分成3组,每组8只,分别为标准饲料喂养组(SD组)、添加黄豆蛋白粉饲养组(Soy组)、添加活性乳清蛋白饲养组(ABD组),观察不同喂养前后小鼠生活状态、体质量、肿瘤体积的变化情况,比较小鼠的平均生存周期,同时检测血液及瘤组织谷胱甘肽含量.结果 实验过程中,三组小鼠均出现了体重下降,ABD组小鼠治疗8周后,体重为(24.35±1.89)g,显著高于Soy组(19.24±2.40)g和SD组(20.04±2.41)g(P<0.05);三组移植瘤体积和瘤组织质量无显著差异;至实验终点,ABD组平均生存周期为(62.13±2.47)天,与Soy组(51.63±10.54)天和SD组(56.00±5.29)天比较,差异均有统计学意义(P<0.05),Soy组和SD组生存期差别无统计学意义(P>0.05);ABD组血液GSH含量明显高于Soy组和SD组(P<0.05),而ABD组瘤组织GSH含量低于Soy组和SD组,但差别无统计学意义(P>0.05).结论 活性乳清蛋白可预防荷瘤鼠的体重下降,明显延长生存期,可能与其防治肿瘤恶液质的发生有关.

Malnutrition and dyscrasia are very common in cancer patients. Malnutrition is associated with poor treatment tolerance, reduced opportunities for treatment, increased complications, increased morbidity and mortality, prolonged hospital stay, and lower survival rate. Malnutrition not only has an impact on the effect of treatment and quality of life, but also cause huge economic losses and waste of social medical resources. Nutrition therapy as a basic methods of clinical treatment and rehabilitation, has been proved by a large number of evidence-based medicine at home and abroad. The evidence shows that the reasonable and effective nutritional support will not increase the rate of tumor recurrence or metastasis rate and lower survival rate, but can significantly improve the postoperative cancer patients nutrition and immune status, reduce the incidence of complications and postoperative infection, improve the cure rate of patients, reduce the mortality rate, reduce drug and medical expenditure, has a positive for most malnourished cancer patients. In order to apply the medical nutrition therapy on patients with cancer to clinical practice, the consensus based on existing research on the relationship between cancer and nutrition at home and abroad, and combined with the status and characteristics of China's diet. Systematically summarize and analyze the influence of dietary nutritional factors on cancer patients and standardize the principles and steps of oncology nutrition treatment. Apply to clinician, clinical nutrition professionals, nurse, and other health care workers.

生酮饮食最早用于脑部疾病的治疗,如脑胶质瘤、癫痫等.近20年研究表明机体内慢性炎症反应、高血糖与肿瘤发展密切相关.运动或限制饮食可降低血糖水平、升高血酮浓度,同时降低炎症反应,而高脂、低糖的生酮饮食方式可模拟运动或禁食产生的生理状态,这使生酮饮食用于治疗代谢性疾病成为可能.随着肿瘤代谢与肿瘤营养相关研究的不断深入,越来越多的证据表明细胞代谢在肿瘤的发生、发展中起着非常重要的作用,加上多种新的实验手段的使用以及信号通路研究的突破,许多研究者认为肿瘤代谢改变或许是肿瘤治疗的新靶点,因而生酮饮食用于肿瘤治疗也逐渐成为研究者近年来关注的焦点.肿瘤细胞依赖葡萄糖作为主要能量来源,而肿瘤患者本身需要摄入更多脂肪和蛋白质,据此,提供足够脂肪和蛋白质、限制葡萄糖的生酮饮食理论上可以治疗肿瘤.生酮饮食利用肿瘤细胞线粒体缺陷、葡萄糖依赖等特征,通过抑制炎症、加强免疫反应、提高抗氧化应激能力、调节相关信号通路蛋白表达等多种途径抑制肿瘤生长,改善患者生活质量,延长患者生存期,同时还能够增强放化疗的敏感性.这些机制为生酮饮食用于肿瘤治疗提供理论基础,但尚有部分机制未完全明确,仍需进一步基础研究及临床试验证实.

目的 尽管TSH被认为和甲状腺癌的发病率和预后密切相关,但是具体潜在机制还没有被阐明.本研究拟探讨乳头状甲状腺癌中TSH是否能调控Cpt1c表达,同时研究TSH对Cpt1c促进乳头状甲状腺癌细胞增殖的影响.方法 首先收集甲状腺癌及其配对的癌旁正常组织标本,利用qRT-PCR法检测Cpt1c基因在35对乳头状甲状腺癌标本及其配对的癌旁正常组织的表达情况;其次分别在浓度梯度和时间梯度上检测TSH对甲状腺癌细胞株B-CPAP中Cpt1c表达的影响;最后构建Cpt1c干扰RNA,转染B-CPAP细胞株,利用免疫印迹法检测和qRT-PCR方法对肿瘤细胞转染干扰RNA效率进行鉴定.鉴定完毕后,利用CCK-8和FACS细胞仪分别检测TSH刺激下的细胞增殖和细胞周期.结果 Cpt1c在乳头状甲状腺癌组织中高表达于正常癌旁组织;TSH可促进乳头状甲状腺癌细胞株B-CPAP中的Cpt1c表达,并且呈浓度依赖性,随着浓度的增高,Cpt1c表达亦增加;Cpt1c干扰可通过S期停滞影响甲状腺癌细胞增殖,同时可通过促进Cpt1c表达引起细胞进入G2期从而引起更强的增殖能力.结论 TSH通过调节Cpt1c表达可以促进乳头状甲状腺癌细胞增殖,Cpt1c基因将来可能成为乳头状甲状腺癌基因治疗的新靶点.

Objective Although ketogenic diet (KD) has been studied its certain anti-tumor effect by basic research and clinical trials, the specific molecular targets or indications which verify its anti-tumor activity are lack. In this study, we examined the expression of different ketolytic key enzymes to identify the sensitivity of KD in tumor cells. Methods Expression of genes encoding 3-hydroxybutyrate dehydrogenase 1 (BDH1) and succinyl-CoA: 3-oxoacid CoA transferase 1 (OXCT1) have been determined in 33 human cancer cell lines by quantitative RT-PCR. HeLa cell and pan-1 cell were selected with high expressing and low expressing two enzymes respectively. Proliferation of HeLa and PANC-1 cells was determined by using a hand-held automatic cell counter after cultured in low glucose medium with or without DL-β-Hydroxybutyric acid sodium salt (βHB). BDH1 and OXCT1 were knocked down in HeLa cells by lentivirus-mediated RNA interference and established HeLa and PANC-1 cell xenograft tumors models in BALB/C nude mice to identify the sensitivity of KD in anti-tumor therapy. Results Compared to control group, proliferation of HeLa and PANC-1 cells in low glucose (LG) was significantly inhibited. Howevere, proliferation of HeLa cells was significantly increased, while added βHB into LG group, but there was no significant effect on proliferation of PANC-1 cells. Animal experiments demonstrated that KD inhibited growth of PANC-1 cell xenograft tumors dramatically, but no effect on the growth of HeLa xenograft tumor. Down-regulation of both BDH1 and OXCT1 in HeLa cells rendered their sensitivity to KD in vitro and in vivo. Conclusions Tumors with low expression of ketolytic enzymes which are not obviously induced gene expression are sensitive to ketogenic metabolic therapy.

支链脂肪酸酯发现背景：促进脂肪细胞从头合成脂类[碳水化合物反应元件结合蛋白（carbohydrate response element binding protein，CHREBP）、酶和葡萄糖转运载体4（glucose transporter 4，GLUT 4）]与增加胰岛素敏感性密切相关；小鼠脂肪细胞过表达GLUT 4（AG4OX）增加循环脂肪酸、增加储脂、降低空腹血糖和增强葡萄糖耐量；循环脂肪酸成分和比例与胰岛素敏感性和葡萄糖耐量密切相关。