Targeting the chromatin structural changes of antitumor immunity

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment

Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.

Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

Receptor tyrosine kinase-like orphan receptor 1:A novel antitumor target in gastrointestinal cancers

Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.

Doxorubicin Stealth Liposomes Prepared with PEG-Distearoyl Phosphatidylethanolamine and Distribution as well as Antitumor Activity in Mice

目的：研制出能够逃避体内网状内皮细胞的阿霉素隐形脂质体，并考察其在生物体内的分布以及比较阿霉素隐形脂质体与阿霉素普通脂质体的抗肿瘤活性。方法：将聚乙二醇－二硬脂酰磷脂酰乙醇胺（PEG－DSPE）同磷脂酰胆碱和胆固醇材料加在一起，用硫酸铵梯度法制备阿霉素隐形脂质体，同法制备阿霉素普通脂质体（但脂膜中不含PEG－DSPE）；通过尾静脉注射给药，比较隐形脂质体阿霉素、普通脂质体阿霉素和游离型阿霉素（盐酸阿霉素注射液）给药后在小鼠各主要脏器组织和血液中的分布情况；采用动物移植性肿瘤实验法，用H22小鼠肝癌细胞接种于小鼠右侧腋皮下形成实体瘤，考察阿霉素隐形脂质体和普通脂质体给药后对实体瘤的瘤重抑制率。结果：通过硫酸铵梯度法制备出了包封率高达95％的阿霉素隐形脂质体；同游离型阿霉素和普通脂质体阿霉素相比，隐形脂质体阿霉素在血液中浓度显著提高，循环时间显著延长，在心脏中分布的浓度显著降低；按5mg·kg^-1剂量治疗，第二天给药和第七天给药治疗方案，阿霉素隐形脂质体给药组的瘤重抑制率均显著高于普通脂质体给药组的瘤重抑制率；按10mg·kg^-1剂量治疗，隐形脂质体给药组的瘤重抑制率比普通脂质体给药组的瘤重抑制率稍高。结论：用普通脂质体给药相比，隐形脂质体阿霉素给药后延长了其在小鼠血液中的循环时间，说明经过PEG－DSPE修饰后的脂质体有逃避网状内皮细胞吞噬的功能（隐形），并且隐形脂质体阿霉素的抗肿瘤活性显著地提高。

白花蛇舌草抗肿瘤的药理机制及药代动力学研究进展

白花蛇舌草具有清热解毒、消痈散结、利水通淋之功,环烯醚萜类、总黄酮类及蒽醌类等是发挥抗肿瘤作用的主要化学成分,对肺癌、肝癌、乳腺癌、结直肠癌等均有明显的抑制作用,其机制与抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡等密切相关。目前对白花蛇舌草的药代动力学研究主要涉及个别单体成分,无法全面反映其药代动力学特征,故本文检索国内外数据库,对近年来白花蛇舌草抗肿瘤作用、药代动力学的研究现状作一综述,旨在为后续采用多成分整合方法研究其体内药代动力学奠定基础,并为其研究开发及临床应用提供一定的参考。

响应面法优化毛木耳粗多糖提取工艺及其抗肿瘤活性评价

采用热水浸提法提取毛木耳粗多糖。以粗多糖得率、总糖含量、生物活性评价为权重指标计算综合评分,采用单因素和响应面试验优化毛木耳粗多糖提取工艺,并评价其抗肿瘤活性。结果表明:最优提取工艺参数为粉碎粒径0.125mm、提取溶液pH9、提取1次、提取温度60℃、料液比1:100(g/mL)、提取时间60min,在此条件下,毛木耳粗多糖的综合评分为64%。抗肿瘤活性试验结果显示,毛木耳粗多糖明显降低了4T1乳腺癌小鼠的肿瘤质量和肺转移结节数,表明其在抗肿瘤活性方面有较好的作用。

乳铁蛋白:作为癌症治疗剂与抗癌药物递送系统的潜力

目前恶性肿瘤疾病频发且呈逐年递增态势,传统药物放化疗方式价格高昂、毒副作用大,且易降低患者耐受性。天然药物在抗肿瘤过程中具有多靶点、高选择性和低毒副作用等优点,是抗肿瘤药物来源的重要途径之一。作为一种多肽类物质,乳铁蛋白具有显著的抗肿瘤作用,而且在纳米药物递送领域发挥巨大作用。乳铁蛋白受体广泛表达于多种癌细胞表面,除其本体具有强烈的抗肿瘤作用外,还广泛用于修饰纳米载体。本文主要综述乳铁蛋白抗肿瘤的机制及其作为抗癌药物递送系统的最新研究进展。

大球盖菇多肽的制备、抗氧化及抗肿瘤活性的研究

[目的]大球盖菇作为近年来在我国迅速崛起的食用菌,以其卓越的营养价值和多样的保健功效受到市场的青睐。然而,尽管其产量迅猛增长,深度加工技术的滞后和创新产品开发的不足已成为制约大球盖菇产业发展的关键因素。因此,本研究旨在优化大球盖菇多肽的制备工艺,并评价其体外抗氧化和抗肿瘤活性,为大球盖菇的深度加工和产品创新提供科学依据。[方法]以蛋白水解度为评价指标,在蛋白酶筛选的基础上,通过单因素和正交试验获得大球盖菇多肽的最佳制备工艺,并通过超滤分级纯化获得3个多肽组分(M1:>10 kDa、M2:3~10 kDa、M3:<3 kDa);通过DPPH·和ABTS^(+)·清除率的测定评价多肽体外抗氧化活性。通过常见肿瘤细胞增殖抑制率的测定评价多肽抗肿瘤活性。[结果]胰蛋白酶酶解制备大球盖菇多肽的最佳工艺为料液比1∶20 g/mL、酶添加量4000 U/g、酶解时间3 h,在该条件下大球盖菇蛋白的水解度为28.31%,比优化前提高了3倍。所制备的大球盖菇多肽对DPPH·和ABTS^(+)·的清除率最高可达69.2%和91.4%,高于以往相关报道。3个多肽组分对4种常见的肿瘤细胞(宫颈癌细胞HeLa、肺癌细胞NCI-H460、乳腺癌细胞BT549、肝癌细胞HepG2)的抑制效果不同,但均呈现浓度依赖性。M1和M3对肺癌细胞NCI-H460的抑制效果最好,而M2主要抑制宫颈癌细胞HeLa;其中,500μg/mL M3对肺癌细胞NCI-H460的抑制率达30.28%。[结论]胰蛋白酶酶解制备大球盖菇多肽的工艺优化后,所制备的多肽具有良好的抗氧化活性和抗肿瘤活性。

Antitumor Activity of the Ganoderma Lucidum Spore Alcohol Extract in Vitro

Several cancer cell lines(epithelioma cells or leukemia cells)from human being or mouse were first used to study the antitumor activity of the Ganoderma lucidum spore alcohol extract(GLSAE)in vitro by the MTT test A comparision was made between the sporodermbroken(SB)and sporoderm nonbroken(SN)GLSAE It was showed that both GLSAE SB and GLSAE SN could inhibit the proliferation of these cancer cells,but the activity of GLSAE SB was much higher than that of GLSAE SN These results suggested that Ganoderma lucidum spore could probably be used for tumor treatment

桑黄饮片联合化疗治疗晚期结直肠癌气血两虚证疗效观察及其对免疫功能的影响

目的观察桑黄饮片联合化疗对晚期结直肠癌气血两虚证患者的临床疗效及对其免疫功能的影响。方法纳入67例符合标准的患者,最终完成有效病例60例,将其分为治疗组和对照组,每组30例;对照组采用奥沙利铂注射液联合卡培他滨片的化疗方案,治疗组在对照组治疗基础上加服桑黄饮片,两组均进行2个周期的治疗;观察两组患者实体瘤疗效、中医症状评分、中医证候疗效、免疫功能指标[CD4^(+)T细胞、CD8^(+)T细胞、CD4^(+)/CD8^(+)、自然杀伤(natural killer,NK)细胞、干扰素(interferon,IFN)-γ、白细胞介素-2、白细胞介素-4、肿瘤坏死因子(tumor necrosis factor,TNF)-α]以及不良反应发生情况。结果治疗组疾病控制率显著高于对照组(P<0.05);治疗后两组患者各项评分均较治疗前显著减少(P<0.05),其中治疗组乏力评分较对照组减少更显著(P<0.05);治疗组中医证候疗效优于对照组(P<0.05)。与治疗前比较,治疗后治疗组CD4^(+)T细胞、NK细胞、IFN-γ水平均显著升高(P<0.05),TNF-α水平显著降低(P<0.05);且治疗组上述指标升高或降低程度均显著大于对照组(P<0.05)。两组不良反应发生情况比较,差异均无统计学意义(P>0.05)。结论桑黄饮片联合化疗能够增强晚期结直肠癌的疗效,提高CD4^(+)T细胞、NK细胞、IFN-γ水平,抑制TNF-α水平,显著缓解患者临床症状,且安全可靠。

Synthesis of Aminoglucose Conjugates of 5-Fluorouracil-1-acetic Acid and 5-Fluorouracil-1-propanoic Acid and Their Antitumor Activities

Six aminoglucose conjugates were synthesized by the reaction of aminoglucose with 5-fluorou-racil-1-acetic acid or 5-fluorouracil-1-propanoic acid and confirmed by IR, 1H NMR and elemental analyses. Their antitumor activities against A2780 cells and PC-14 cells were also evaluated.

厚朴酚抗肿瘤作用研究概述

厚朴酚对肝癌、骨癌、结直肠癌、食管癌、肺癌、乳腺癌、脑癌等均有较好的抑制作用,其抗肿瘤作用机制主要有抑制肿瘤细胞增殖、促进肿瘤细胞凋亡、抑制肿瘤细胞迁移等,此外厚朴酚能诱导肿瘤细胞自噬、逆转肿瘤细胞耐药性、影响葡萄糖代谢和逆转肌肉萎缩。厚朴酚可通过多种途径发挥抗肿瘤作用,在抗肿瘤治疗领域有广阔的应用前景。参考文献76篇。

Preliminary screening of antimicrobial and antitumor activities from cultivated microalgaes

Hydrophilic and lipophilic extracts were prepared from 8 microalgal strains, and screened for antimicrobial and antitumor activities. Antimicrobial activity was determined by observing bacterial （ S. aureus, Bacillus subtilis and Escherichia coh~ and fungal（Aspergillus niger and Penicillium chrysogenum） growth inhibition. All the microalgae had different degrees of antimicrobial activity against one or more microbe - tested, and 56.47% of the extracts showing the anti-S.aureus activity exhibited the antibacterial activity against （MRSA）. Cytotoxic activities were measured in vitro against human cancer cell lines HeLa by the MTT assay. Most of these extracts showed potent activity against the growth of the tumor cells, especially the intracellular lipophilic extracts from Isochrysis galbana Parke 3011 and Isochrysis galbana Parke H29, which exhibited strong antitumor activity against HeLa cell lines. The overall results of this study indicate that the extracts from microalgae represent a potential sources of medicine for the treatment of infectious and cancer diseases.

Antitumor Actinity of Puqietinone,a Novel Alkaloid fromthe Bulbs of Fritillaria puqiensis

从蒲圻贝母中分得的一种新生物碱蒲贝酮碱，按一定剂量灌胃给药，显示了强的抗小鼠艾氏腹水癌（ＥＡＳ，实体型），宫颈癌（Ｕ＿（１４），实体型）及肝癌（ＨｅＰＡ，实体型）的活性。

核桃枝的抗氧化、抗菌及抗肿瘤活性研究

【目的】评估核桃枝不同溶剂提取液的抗氧化、抗菌及抗肿瘤活性,为林业废弃物资源综合利用提供理论依据。【方法】采用不同的溶剂(水、丙酮和乙醇)进行提取,通过红外光谱和液相色谱-四级杆-高分辨串联质谱解析核桃枝中的化学成分;采用DPPH自由基、ABTS自由基和OH自由基清除法评估不同溶剂提取液的体外抗氧化能力;采用二倍稀释法检测提取液的抗菌能力;采用cell counting kit-8(CCK8)法检测提取液对宫颈癌细胞(Hela)、肝癌细胞(HepG2)、乳腺癌细胞(MCF-7)和胃癌细胞(SGC-7901)细胞的抗肿瘤活性。【结果】在3种溶剂提取液中,黄酮类、糖类、萜类及生物碱类等物质的含量均相对较高,生物医药类活性成分含量所占比例最高的是乙醇提取液,达到了86.88%;提取液的抗氧化能力随着质量浓度的升高而逐渐增强,抗氧化能力由强到弱依次是乙醇提取液、水提取液、丙酮提取液。乙醇提取液和丙酮提取液对蜡状芽孢杆菌和金黄色葡萄球菌都有较强的抑制作用,且乙醇提取液抑制大肠杆菌、沙门氏菌和枯草芽孢杆菌的效果强于丙酮提取液。提取液在抗肿瘤能力由强到弱依次是乙醇提取液、丙酮提取液、水提取液,且乙醇提取液对Hela、HepG2、MCF-7和SGC-7901细胞的抑制作用最显著,致死率分别为98.83%、99.08%、98.44%、98.74%。【结论】核桃枝含有多种抗氧化、抗菌和抗肿瘤活性成分,在功能食品或生物医药领域具有良好的开发潜能。

Synthesis and Antitumor Activity of an Analog of Phthalascidin

An analog of phthalascidin （Pt-650） was synthesized with an improved synthetic route. With precursor 2 as the starting material, compound 1 was prepared through 4 steps in a total yield of 47%. In vitro antitumor test of this Pt-650 analog showed that it possessed strong toxicity against a number of tumor cell lines including A2780, A549, Bel-7402, BGC-823, HELA, KB, KeTr3 and HCT-8.

Therapeutic potential of kakkatin derivatives against hepatocellular carcinoma

In this article,we commented on the work done by Jiang et al,where they syn-thesized a kakkatin derivative,6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-me-thoxy-4H-chromen-4-one(HK),and investigated its antitumor activities and me-chanism in gastric cancer MGC803 and hepatocellular carcinoma(HCC)SMMC-7721 cells.HK was evaluated for its antitumor activity as compared to kakkatin and cisplatin.This article focused on various risk factors of HCC,the mechanism of HCC progression and molecular targets of the kakkatin derivative,and limi-tations of available treatment options.HCC is a predominant form of primary liver cancer characterized by the accumulation of multiple gene modifications,overexpression of protooncogenes,altered immune microenvironment,and infilt-ration by immune cells.Puerariae flos(PF)has been used in traditional medicine in China,Korea,and Japan for lung clearing,spleen awakening,and relieving alcohol hangovers.PF exerts antitumor activity by inhibiting cancer cell prolif-eration,invasion,and migration.PF induces apoptosis in alcoholic HCC via the estrogen-receptor 1-extracellular signal-regulated kinases 1/2 signaling pathway.Kakkatin isolated from PF is known as a hepatoprotective bioflavonoid.The ka-kkatin derivative,HK,exhibited anticancer activity against HCC cell lines by in-hibiting cell proliferation and upregulating nuclear factor kappa B subunit 1 and phosphodiesterase 3B.However,further preclinical and clinical studies are required to establish its therapeutic potential against HCC.

Antitumor Alkaloids Isolated from Tylophora ovata

Four phenanthroindolizidine alkaloids, named tylophoridicine A (1), tylophorinine (2), O_methyl tylophorinidine (3) and tylophorinidine (4), were isolated from the roots of Tylophora ovata (Lindl.) Hook. ex Steud. Using modern NMR techniques including NOESY and 1H_NMR line broadening effect experiments, CD spectra and MS analysis as well as chemical methods, their structures were identified as (13aR)_6_hydroxy_3,7_dimethoxy_phenanthroindolizidine (1), (13aS,14R)_14_hydroxy_3,6,7_trimethoxy_phenanthro_indolizidine (2), (13aS,14S)_14_hydroxy_3,6,7_trimethoxy_phenanthroindolizidine (3), and (13aS,14S)_6,14_dihydroxy_3,7_dimethoxy_phenanthroindolizidine (4) respectively. Compound 1 is a new compound, compounds 2-4 are obtained from this plant for the first time. Compounds 1, 3 and 4 showed strong antitumor activities.

Animal Experiment Study on Antitumor Effect of Matrine Liposome

Objective： To study the antitumor effect of matrine liposome in mice. Methods： The mice were selected as the research object, and SPSS （statistic package for social science）, matrine and matrine liposome were used for grouping. The antitumor effects of EAC, S 180 and H22 were evaluated by tumor weight, thymus weight and spleen weight. Results： The inhibitory effect of matrine liposome on EAC, S180 and H22 in mice was significantly higher than matrine, P 〈 0.05, which had statistical significance. Conclusion： Matrine liposome can effectively enhance the anti-tumor effect and improve the immunity of animals, which is worthy of clinical promotion.