灵芝多糖精粉制备技术的研究

该项目进行了灵芝液体深层培养和多糖分离提取工艺的研究,并开展了灵芝多糖精粉制备技术的研究.通过动物实验对从灵芝菌丝培养物提取和制备的灵芝多糖精粉的免疫功能和抗肿瘤活性进行了研究,实验结果表明:灵芝多糖精粉作为刺激源,可促进巨噬细胞和B淋巴细胞的免疫功能;与抗癌药物环磷酰胺合用时,还可增强其抑制肿瘤的效能.     

灵芝多糖精粉制备技术的研究

该项目进行了灵芝液体深层培养和多糖分离提取工艺的研究,并开展了灵芝多糖精粉制备技术的研究.通过动物实验对从灵芝菌丝培养物提取和制备的灵芝多糖精粉的免疫功能和抗肿瘤活性进行了研究,实验结果表明灵芝多糖精粉作为刺激源,可促进巨噬细胞和B淋巴细胞的免疫功能;与抗癌药物环磷酰胺合用时,还可增强其抑制肿瘤的效能.     

美洲大蠊酶解液冻干粉多糖含量测定及药理活性研究

研究了美洲大蠊酶解液冻干粉(LPEHPA)多糖含量及对多种肿瘤细胞株增殖的抑制作用、对非洲绿猴肾细胞株的抗氧化作用以及对脂多糖(LPS)诱导的小鼠巨噬细胞的抗炎作用。采用水提酶解法提取美洲大蠊的有效成分,通过苯酚硫酸法测定多糖含量,MTT法测定其对Bel-7402、A549、M231及MCF-7四种不同的肿瘤细胞株的抑制率;建立过氧化氢诱导的氧化损伤模型,MTT法观察药物介入后的细胞存活率;酶联免疫法检测细胞上清液中炎症因子TNF-α和IL-6的浓度。结果 LPEHPA中多糖含量为4.72%;对四种肿瘤细胞最高抑制率分别为65.02%、76.05%、62.92%和65.10%;LPEHPA对非洲绿猴肾细胞株(Vero)有明显保护作用,浓度为1 mg·mL-1时,与对照组相比细胞存活率提升了37.52%;脂多糖诱导炎症后,与模型组相比,加药组TNF-α、IL-6浓度显著减少,与空白组相比具有显著性差异。通过对LPEHPA药理活性结果分析,LPEHPA在机体可承受毒性范围内,具有良好的抗肿瘤、抗氧化及抗炎活性。     

苦参碱和氧化苦参碱抗肿瘤作用机制研究进展

苦参碱和氧化苦参碱是一类生物碱,具有多方面药理活性。目前国内外关于苦参碱和氧化苦参碱抗肿瘤作用的研究表明:苦参碱和氧化苦参碱通过抑制肿瘤细胞DNA的合成、影响肿瘤细胞的正常周期来抑制肿瘤细胞的增殖;通过影响与肿瘤细胞相关基因的表达、抑制相关酶的活性等诱导肿瘤细胞发生凋亡。因此,这种生物碱对抗肿瘤作用的研究受到了极大的关注。就近年来对苦参碱和氧化苦参碱抗肿瘤作用的研究作一简要综述,概括其对各种癌细胞的抗肿瘤作用机制。     

香菇多糖对小鼠脾LAK细胞增殖及活性的影响

<正>自LAK细胞问世以来，LAK细胞与IL-2联合回输治疗肿瘤已取得良好效果。但此疗法需要大量效应细胞及IL-2，价格昂贵且副作用大。因此，增强LAK细胞活性，减少IL-2用量，已成为一项重要的课题。香菇多糖是从香菇的菌丝体提取的高分子葡聚糖，除具有抑制肿瘤生长、转移作用外，对机体免疫功能具有调节作用。临床上已作为免疫增强剂，用于肿瘤和慢性肝炎的辅助治疗。但有关香菇多糖对LAK细胞活性的调节作用尚未见报道。为此我们研究了注射香菇多糖小鼠脾LAK细胞增殖及抗肿瘤活性的作用。     

灵芝多糖精粉制备技术的研究

该项目进行了灵芝液体深层培养和多糖分离提取工艺的研究,并开展了灵芝多糖精粉制备技术的研究。通过动物实验对从灵芝菌丝培养物提取和制备的灵芝多糖精粉的免疫功能和抗肿瘤活性进行了研究,实验结果表明:灵芝多糖精粉作为刺激源,可促进巨噬细胞和B淋巴细胞的免疫功能;与抗癌药物环磷酰胺合用时,还可增强其抑制肿瘤的效能。     

药用植物内生真菌多糖研究进展

真菌多糖具有多种生理活性,广泛应用于医药、农业、食品等行业。基于植物内生真菌生长过程中会产生与宿主相同或相似的生理活性成分,药用植物生理活性的多样性赋予了其内生真菌活性的多样性,药用植物内生真菌是开发新型天然活性多糖的资源宝库。综述了近些年来关于药用植物内生真菌作为诱导子调节植物生长、代谢及其体外抗氧化、抗肿瘤、抑菌、降血糖等多种生理作用的研究进展。并对今后的研究方向进行展望,以期为药用植物内生真菌多糖的开发利用提供参考。     

铁皮石斛多糖抗癌及免疫活性研究

研究了铁皮石斛多糖的抗癌及免疫活性。水提醇沉法提取铁皮石斛多糖,将其作用于癌细胞株(HepG2、A549、F9、NCCIT)和小鼠脾脏细胞、腹腔巨噬细胞,观察细胞形态变化,并用MTT法分析其对细胞增殖的作用。结果表明:铁皮石斛多糖能抑制癌细胞的增殖并促进脾脏细胞生长,铁皮石斛多糖具有一定的抗癌活性及免疫活性。     

羊肚菌多糖提取工艺研究进展

羊肚菌是药食两用菌,多糖是其主要功能成分之一,具有抗氧化、抗衰老、抗肿瘤、抗疲劳、抗菌、降血脂和调节免疫等多种功能活性。本研究对羊肚菌多糖提取工艺进行综述,为羊肚菌多糖的开发应用和进一步研究提供参考。     

氨基酸在抗肿瘤药物修饰研究中的设计合成及其活性研究

氨基酸是生命活动中最基本的物质,是生命代谢的物质基础,肿瘤细胞对氨基酸的需求远大于正常组织.将氨基酸引人抗肿瘤药物分子中,可以提高其对肿瘤细胞的选择性,增强药物的脂溶性、缓解药物对细胞的毒性等.越来越多的药学工作者相继用氨基酸对各抗肿瘤药物进行结构修饰,并对其活性进行研究,以求寻找到更有利于癌症患者的高效、低毒的抗肿瘤药物.     

荷瘤小鼠骨髓来源的树突状细胞诱导产生的抗肿瘤免疫反应

目的研究荷瘤小鼠骨髓来源的树突状细胞（ＤＣ）是否具有诱导机体产生抗肿瘤免疫反应的能力, 与正常小鼠骨髓来源的ＤＣ有无差异。方法于体外用ｍＧＭ－ＣＳＦ和ｍＩＬ－４分别从正常小鼠和荷Ｃ２６肿瘤的小鼠骨 髓细胞诱导产生ＤＣ,观察它们刺激同种Ｔ细胞、同基因Ｔ细胞增殖的能力,以及由二者免疫所诱导产生的ＣＴＬ的 杀伤活性。结果荷瘤小鼠骨髓来源的ＤＣ与正常小鼠骨髓来源的ＤＣ在刺激同种Ｔ细胞增殖、刺激同基因Ｔ细胞 增殖的能力和诱导产生ＣＴＬ的杀伤活性差异无显著意义。结论荷瘤小鼠骨髓来源的ＤＣ与正常鼠骨髓来源的 ＤＣ具有相似的诱导产生抗肿瘤免疫反应的能力,提示可以从荷瘤机体的ＤＣ前体诱导产生有抗瘤能力的ＤＣ,用于 抗肿瘤免疫治疗。     

Immunomodulation by Inflammation during Liver and Gastrointestinal Tumorigenesis and Aging

Chronic inflammation is thought to promote tumorigenesis and metastasis by several mechanisms, such as affecting tumor cells directly, establishing a tumor-supporting microenvironment, enhancing tumor angiogenesis, and suppressing antitumor immunity. In this review, we discuss the recent advances in our understanding of how inflammation induces the immunosuppressive tumor microenvironment, such as increasing the level of pro-inflammatory cytokines, chemokines, and immunosuppressive molecules, inducing immune checkpoint molecules and cytotoxic T-cell exhaustion, and accumulating regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs). The suppression of antitumor immunity by inflammation is especially examined in the liver and colorectal cancer. In addition, chronic inflammation is induced during aging and causes age-related diseases, including cancer, by affecting immunity. Therefore, we also discuss the age-related diseases regulated by inflammation, especially in the liver and colon.     

Extracellular Vesicles and Their Role in the Spatial and Temporal Expansion of Tumor–Immune Interactions

Extracellular vesicles (EVs) serve as trafficking vehicles and intercellular communication tools. Their cargo molecules directly reflect characteristics of their parental cell. This includes information on cell identity and specific cellular conditions, ranging from normal to pathological states. In cancer, the content of EVs derived from tumor cells is altered and can induce oncogenic reprogramming of target cells. As a result, tumor-derived EVs compromise antitumor immunity and promote cancer progression and spreading. However, this pro-oncogenic phenotype is constantly being challenged by EVs derived from the local tumor microenvironment and from remote sources. Here, we summarize the role of EVs in the tumor–immune cross-talk that includes, but is not limited to, immune cells in the tumor microenvironment. We discuss the potential of remotely released EVs from the microbiome and during physical activity to shape the tumor–immune cross-talk, directly or indirectly, and confer antitumor activity. We further discuss the role of proinflammatory EVs in the temporal development of the tumor–immune interactions and their potential use for cancer diagnostics.     

铁棒锤总生物碱、3-乙酰乌头碱和宋果灵抗肿瘤活性研究

本文从铁棒锤总生物碱中提取分离得到3-乙酰乌头碱和宋果灵,应用MTT比色法研究药物的细胞毒型、细胞形态学实验方法观察细胞形态、流式细胞术分析细胞凋亡和细胞周期,激光共聚焦从形态上分析细胞的凋亡等多方面对其抑制人肝癌细胞的生理活性进行研究。3-乙酰乌头碱和宋果灵的抗肿瘤细胞研究表明,随着浓度的逐步增加,其抗肿瘤效果逐步增强;药物作用于人肝癌细胞后,细胞数量明显减少,具有明显的抑制HepG2生长的能力,并且使细胞发生早期凋亡和晚期凋亡的比率增大,随处理时间的延长细胞G1期细胞逐渐增多,G2期和S期细胞逐渐减少。3-乙酰乌头碱和宋果灵的体外抗肿瘤实验研究初步证实了其具有抑制肿瘤细胞增殖、诱导肝癌细胞凋亡的作用,显示3-乙酰乌头碱和宋果灵可能成为新的肝癌细胞凋亡诱导剂,为寻找新型抗肿瘤药物的先导化合物奠定了基础。     

Combination of Immunotherapy and Photo-pyroptosis as Novel Anticancer Strategy

Immunotherapy has made great progress in clinical cancer treatment in recent years, but its therapeutic efficacy is significantly limited by the lack of immunogenicity in the tumor microenvironment. Pyroptosis is a type of programmed cell death in which the dying cancer cells produce inflammatory cytokines to relieve the immuno-suppressive microenvironment and thus increase anti-tumor immunity. Reactive oxygen species (ROS) produced during photodynamic therapy (PDT) are one of the efficient activators that induce pyroptosis. Recently, a few photosensitizers have emerged with the ability to induce immunogenic cancer cell death via pyroptosis, opening a new field for PDT. This highlight introduces the latest research on antitumor strategies achieved by the combination of immunotherapy and photodynamic therapy through photo-pyroptosis.     

Imidazole Analogs of Vascular-Disrupting Combretastatin A-4 with Pleiotropic Efficacy against Resistant Colorectal Cancer Models

Specific targeting of the tumoral vasculature by vascular-disrupting agents (VDA), of which combretastatin A-4 (CA-4) is a main representative, has been considered a new therapeutic strategy against multidrug-resistant tumors. In addition, CA-4 and analogs are tubulin-targeting agents and can exert direct antitumor effects by different mechanisms. Herein, we analyzed a series of synthetic CA-4 analogs featuring N-methylimidazole-bridged Z-alkenes with different halo- or amino-substituted aryl rings in vitro and in vivo, focusing on models of colorectal cancer. Combined in vitro/in vivo structure–activity relationship studies using cell lines and xenograft tumors susceptible to VDA-induced vascular damage demonstrated a clear association of cytotoxic and vascular-disrupting activity with the ability to inhibit tubulin polymerization, which was determined by specific substitution constellations. The most active compounds were tested in an extended panel of colorectal cancer (CRC) cell lines and showed activity in CA-4-resistant and chemotherapy-resistant cell lines. The bromo derivative brimamin was then compared with the known fosbretabulin (CA-4P) by activity tests on DLD-1- (multidrug-resistant) and HT29- (CA-4-resistant) derived xenograft tumors. Treatment did not induce pronounced vascular-disrupting effects in these tumors. Histological analyses revealed distinct tumor substructures and vessel compositions of DLD-1/HT29 tumors, which clearly differed from the tumor models susceptible to VDA treatment. Even so, brimamin effectively retarded the growth of DLD-1 tumors, overcoming their resistance to standard treatment, and it inhibited the outgrowth of disseminated HT29 tumor cells in an experimental metastasis model. In conclusion, combretastatin analogous N-methylimidazoles proved capable of inducing vascular-disrupting effects, comparable to those of CA-4P. In addition, they showed antitumor activities in models of drug-resistant colorectal cancer, independent of vascular-disrupting effects.     

FLLL32 Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells by Regulating the p38 Pathway

Oral cancer is the most common oral malignant tumor in Taiwan. Although there exist several methods for treatment, oral cancer still has a poor prognosis and high recurrence. FLLL32, a synthetic analog of curcumin with antitumor activity, is currently known to induce melanoma apoptosis and inhibit tumor growth in various cancers. However, few studies have examined the mechanisms of FLLL32 in oral cancer. In this study, we explore whether FLLL32 induces apoptosis in oral cancer. We determined that FLLL32 can inhibit the cell viability of oral cancer. Next, we analyzed the effect of FLLL32 on the cell cycle of oral cancer cells and observed that the proportion of cells in the G2/M phase was increased. Additionally, annexin-V/PI double staining revealed that FLLL32 induced apoptosis in oral cancer cells. Data from the Human Apoptosis Array revealed that FLLL32 increases the expression of cleaved caspase-3 and heme oxygenase-1 (HO-1). FLLL32 activates proteins such as caspase-8, caspase-9, caspase-3, PARP, and mitogen-activated protein kinases (MAPKs) in apoptosis-related molecular mechanisms. Moreover, by using MAPK inhibitors, we suggest that FLLL32 induces the apoptosis of oral cancer cells through the p38 MAPK signaling pathway. In conclusion, our findings suggest that FLLL32 is a potential therapeutic agent for oral cancer by inducing caspase-dependent apoptosis and HO-1 activation through the p38 pathway. We believe that the activation of HO-1 and the p38 pathway by FLLL32 represent potential targets for further research in oral cancer.