Anti-tumor Effects of a Recombinant Fowlpox Virus Expressing Apoptin on Human Cervical Carcinoma in Vivo and in Vitro

Apoptin is a chicken anemia virus-derived,p53-independent,bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis of various human tumor cells,but not of normal diploid cells.To explore the application of apoptin in tumor gene therapy,we used a recombinant fowlpox virus expressing apoptin protein （vFV-Apoptin） to investigate the anti-tumor effectes of vFV-Apoptin on human cervical carcinoma（HeLa） cells in vivo and in vitro through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide（MTT） assay,acridine orage/ethidium bromide（AO/EB） and annexin V staining test,respectively.The results show that vFV-Apoptin inhibites the proliferation of HeLa cells in vitro through inducing the apoptosis of HeLa cells,and the inhibition effect of vFV-Apoptin has a dose-effect and time-effect relationship.The results of animal models show that vFV-Apoptin significantly inhibits tumor growth,extends the lifespan of animals and improves the mean survival.Experimental results indicate that vFV-Apoptin has a potential application in the tumor gene therapy.

Anti-tumor Effect and Mechanism of SEA-Fab’ Coupled Protein on Gastric Tumor

Summary： The anti-tumor effect and mechanism of SEA-Fab＇ coupled protein on gastric tumor was studied. The target cell Walke-256 was treated with SEA-Fab＇ synthesized chemically or SEA respectively for 24 h, 36 h or 72 h. PBMC＋Walke-256 cells served as controls. The apoptotic index of SEA-Fab＇ against effector cells was detected. In the mouse gastric cancer models （n=60）, SEA-Fab＇, SEA and normal saline was injected in experimental group, SEA group and control group respectively. The occurrence and weight of tumor was observed. The results showed that the apoptotic index was significantly higher in the SEA-Fab＇ （34.6 -68.9%） and SEA group （15.5-31.9%） than in PBMC＋Walker-256 group （5.5%-12.8%） with the difference being significant （P〈0.01）. And there was significant difference between SEA-Fab＇ group and SEA group （P〈0.01）. The tumor weight in SEA-Fab＇, SEA and control groups was 3.6±0.53 g, 0. 78±0. 26 g and 0.49±0. 17 g respectively with the difference being statistically significant between the SEA-Fab＇ group, SEA group and the control group （P〈0.01）. In the SEA-Fab＇s and SEA groups, there were CD4^＋ T and CD8^＋ T cell infiltrates, but in the cotnrol group, no or few T lymphocytes were seen in the mouse tumor tissue. It was concluded that SEA-Fab＇ was more effective to activate T lymphocytes to kill the tumor cells than SEA used alone. It was feasibility by using the monoclonal antibody as carrier to perform the targeted Immunotherapy of gatric tumor.

Clinical Observation on the Improved Short-Term Effects of Anti-Tumor Purified Chinese Medicine Injection Ai-Jing for 138 Cases with Malignant Tumors

The subjects of this study were to observe the improved short-term effects of anti-tumor purified Chinese medicine injection Ai-Jing for 138 cases with malignant tumors. This was a multi-center clinical study, and a total of 138 patients included 96 males and 42 females, with the age from 60 to 76 years. Ai-Jing has obtained the Chinese invention patent since 2008 (ZL991-03528.3). A novel technique acupoint injection method was adopted. Except for lung cancer, patients with other malignant tumors were injected once every other day, 2 ml each time. A course of treatment needs 6 Ai-Jing injections, lung cancer patients need 10 - 20 Ai-Jing injections. At the same time, patients were treated with traditional medicine decoction. Due to the limited number of cases, cure rate, recovery rate and remission rate were calculated as a whole, respectively 18.12%, 44.20% and 32.15%. All the invalid patients were lung cancer, accounting for 16.67% of the patients treated with lung cancer, and the total treatment inefficiency was 6.52%. Conclusion: Chinese Medicine Injection Ai-Jing extracts the effective components of anti-cancer and tumorigenesis, and has the effects of anti-cancer and tumorigenesis, anti-inflam-matory and analgesic, and repairing body damage, with small toxic and side effects and low cost.

Safety of anti-tumor necrosis factor therapy during pregnancy in patients with inflammatory bowel disease

Treatment of inflammatory bowel disease has significantly improved since the introduction of biological agents, such as infliximab, adalimumab, certolizumab pegol, and golimumab. The Food and Drug Administration has classified these factors in category B, which means that they do not demonstrate a fetal risk. However, during pregnancy fetuses are exposed to high anti-tumor necrosis factor(TNF) levels that are measurable in their plasma after birth. Since antibodies can transfer through the placenta at the end of the second and during the third trimesters, it is important to know the safety profile of these drugs, particularly for the fetus, and whether maintaining relapse of the disease compensates for the potential risks of fetal exposure. The limited data available for the anti-TNF drugs to date have not demonstrated any significant adverse outcomes in the pregnant women who continued their therapy from conception to the first trimester of gestation. However, data suggest that antiTNFs should be discontinued during the third trimester, as they may affect the immunological system of the newborn baby. Each decision should be individualized, based on the distinct characteristics of the patient and her disease. Considering all the above, there is a need for more clinical studies regarding the effect of antiTNF therapeutic agents on pregnancy outcomes.

Effect of Allicin in Antagonizing Mice's Bladder Cancerin vitro and in vivo

Objective: To explore anti-tumor effect and mechanism of Allicin in treating murine bladder tumor. Methods: To observe Allicin's effect on MBT-2 tumor cells in vitro, 100 μg/ml Allicin was added to the tumor cell culture, and the morphology of tumor cells was observed by phase contrast microscope 6 hrs later. The direct effects of Allicin on tumor cell growth in vitro in the MTT Assay was also evaluated. To determine anti-tumor effect of Allicin in vivo, C3H/He mice were randomly grouped prior to initiation of experiment. The mice received 1×105 MBT-2 cells administered subcutaneously into the right posterior flank on the Day 0 the experiment started. Allicin was injected at the site near tumor transplantation on the Day 1. The mice were examined for tumor development and the tumors were measured in two dimensions with calipers twice a week. On Day 21 the tumors were resected and examined pathologically to see the immune response. Results: The observation of morphology of MBT-2 cells in vitro and MTT assay indicated that Allicin has apparent direct cytotoxicity to bladder cancer cells. In high dosage group, a marked delay was shown in the appearance and growth of tumors after subcutaneously injection when compared with the control group (P<0.01). Histology studies suggested that there were more macrophages, lymphocytes and fibroblasts at the peri-tumor region than the control group. Conclusion: Allicin has a marked tumor inhibitory effect on bladder tumor. This effect could possibly be related to direct cytotoxicity and activation of immune response. It could as possibly prove to be an effective intravesical treatment agent for superficial bladder cancer.

小檗碱抗脑瘤和头颈部肿瘤的药理作用研究进展

小檗碱具有广泛的药理活性,除抗炎、抗感染、降血糖、调血脂、心脏保护等作用外,对胃癌、乳腺癌、膀胱癌、肝癌等还具有显著的抗肿瘤作用,是一个潜在的抗肿瘤药物。该文主要围绕小檗碱对甲状腺癌、鼻咽癌、口腔鳞癌、舌癌、喉癌、腺样囊性癌等头颈部肿瘤和脑癌的药理作用及其机制进行了综述和分析,为小檗碱的后续开发提供理论支撑。

小檗碱抗胃癌的药理作用及其机制研究进展

胃癌的发病率和死亡率在我国各种恶性肿瘤中均位居第三,是威胁人民生命健康的重要杀手。小檗碱除具有抗炎、抗感染、调节心血管等作用外,对肝癌、结直肠癌、脑瘤、头颈部肿瘤、泌尿系肿瘤等也有较好的作用,因而可能是一个潜在的抗肿瘤药物。该文主要从小檗碱预防胃癌的发生,以及对SGC7901、BGC-823、MKN-45等人胃癌细胞的抑制和诱导凋亡等方面进行了综述,以期为小檗碱的进一步临床开发提供参考。

藤黄属植物笼状呫吨酮类化学成分与抗肿瘤作用研究进展

目的为藤黄属植物中笼状呫吨酮类化合物与抗肿瘤作用的研究提供参考。方法以“藤黄属”“笼状呫吨酮”“化学成分”“抗肿瘤作用”为关键词,采用计算机检索中国知网和PubMed数据库中1995年至2023年的相关文献,总结藤黄属植物中分离出的笼状呫吨酮类化合物的化学成分和抗肿瘤作用。结果笼状呫吨酮类化合物为藤黄属植物的特征性化学成分,取代基主要有异戊烯基、异戊二烯基、羧基、羟甲基、甲氧基、羟基等,具有抗肿瘤、抗菌、抗炎等作用,其中抗肿瘤活性研究最广泛。结论笼状呫吨酮类化合物的合理开发和利用可为天然抗肿瘤化合物的筛选提供参考。

人LIGHT和HSV-TK-EGFP基因共转染的MSCs抗肿瘤免疫的体内研究

目的研究与单纯疱疹病毒的糖蛋白D竞争结合单纯疱疹病毒进入介导物(herpes virus entry mediator,HVEM)的淋巴毒素类似物(homologous to lymphotoxins,exhibits inducible expression,and competes with HSV glycoprotein D for HVEM,a receptor expressed by T lymphocytes,LIGHT)基因和单纯疱疹病毒胸苷激酶(herpes simplex virus thymidine kinase,HSV-TK)基因共转染的骨髓间充质干细胞(mesenchymal stem cells,MSCs)在体内的抗肿瘤免疫功能。方法将pIRES2-LIGHT基因和HSV-TK-EGFP基因共转染小鼠骨髓间充质干细胞(MSCs/LT组),以转染空载体和转染HSV-TK-EGFP基因的骨髓间充质干细胞作对照。流式细胞仪检测LIGHT分子和HSV-TK-EGFP分子在稳定转染的骨髓间充质干细胞上的表达。体内迁移实验观察MSCs/LT在小鼠体内迁移情况。观察更昔洛韦注射前后MSCs/LT对荷瘤小鼠体内肿瘤的治疗作用。ELISA法检测小鼠肿瘤组织中IFN-γ,IL-2和IL-10的水平。结果流式细胞仪检测发现,MSCs/LT能稳定高表达LIGHT分子。MSCs/LT有特异地向肿瘤组织趋化的特性。MSCs/LT和MSCs/T有较好的抑制肿瘤生长的能力,但在更昔洛韦诱导后,MSCs/LT的抗肿瘤效应下降甚至消失。同时,MSCs/LT可促使T细胞进入肿瘤组织,并促进T细胞分泌IL-2、IFN-γ,抑制IL-10分泌(P<0.05)。结论共转染人LIGHT和HSV-TK-EGFP基因的骨髓间充质干细胞能稳定高表达LIGHT分子,能特异性地向荷瘤小鼠体内肿瘤组织趋化并抑制肿瘤的生长,这种体内抗肿瘤功能可能与促进T淋巴细胞IL-2、IFN-γ等细胞因子的分泌,改善局部免疫抑制环境有关。

小檗碱抗食管癌和肉瘤的药理作用及其机制研究进展

小檗碱是一种具有广泛药理作用的生物活性物质,除了抗炎、抗菌、抗病毒、抗腹泻、抗高血压、抗缺氧、降血糖、降血脂等作用外,还具有抗肿瘤作用。既往已有小檗碱抗胃癌、结直肠癌、皮肤癌、胰腺癌等的相关报道,该文主要就小檗碱抗食管癌和肉瘤的药理作用及其机制进行了综述,并做了相关点评和分析。

小檗碱抗皮肤癌药理作用及其机制的研究进展

小檗碱是一种具有广泛药理作用的生物活性物质,除了抗炎、抗菌、抗病毒、抗腹泻、抗高血压、抗缺氧、降血糖和降血脂等作用外,还具有广谱抗肿瘤作用。该文主要从小檗碱一直皮肤癌的形成,以及抑杀皮肤黑色素瘤细胞和人皮肤鳞癌A431细胞等方面进行了综述和分析,为小檗碱在皮肤癌方面的进一步研究提供参考。

姜黄素与抗肿瘤药物联合应用的研究进展

联合用药能显著弥补单药使用的不足并能加快开发治疗复杂性疾病的新治疗方案.姜黄素是一种1,3-二酮类化合物,具有多种药理活性,其中抗肿瘤作用得到广泛关注.姜黄素能够抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡等,具有毒性低、耐受性好等特点.研究发现:姜黄素与临床抗肿瘤药物联合应用具有一定的协同作用,能有效地抑制癌细胞生长,降低药物的毒副作用,减少药物剂量,达到增效减毒的效果.本文在细胞和实验动物水平上总结了姜黄素与抗肿瘤药物联合应用所产生的影响及可能的作用机制.

Nrf2/HO-1信号通路对消化道恶性肿瘤影响的研究

消化道恶性肿瘤包括胃癌、肝癌、结直肠癌、胰腺癌等,该类疾病给患者造成了严重的身心健康损害,是人类医学进步必须克服的难题。核转录因子红系2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路对消化系统恶性肿瘤的各种细胞和动物模型中的氧化损伤、铁死亡、焦亡、诱导细胞自噬及促进血管生成有关键作用。随着生物科学技术的进步,使用先进技术提取天然化合物和药物对该信号通路的调节在临床前研究中显示出潜在的抗肿瘤价值。本文就Nrf2/HO-1信号通路对消化道肿瘤影响的最新研究进展进行简单的综述。

鬼箭羽化学成分和药理作用的研究进展及其质量标志物预测

鬼箭羽始载于《神农本草经》,列为中品,具有通经、破血、杀虫和散瘀止痛等功效。现代药理学研究表明其具有降血糖、抗肿瘤、抗炎镇痛、抗菌、抗氧化、抗病毒等药理作用,其活性成分以黄酮类和萜类成分为主。本文通过对鬼箭羽的化学成分、药理作用、毒理等方面进行综述,并基于此,从植物亲缘关系、化学成分有效性、化学成分可测性等方面对鬼箭羽的质量标志物进行推测分析,初步预测芦丁、槲皮素、香橙素、儿茶素、β-谷甾醇、鬼箭羽二萜A和11-羰基-β-乳香酸等成分可作为鬼箭羽潜在的质量标志物,以期为鬼箭羽的质量控制和临床用药规范提供科学依据。

双氢青蒿素抗消化道恶性肿瘤作用及机制研究进展

中国是消化道肿瘤较为流行的国家,尽管近十年来在肿瘤筛查、诊断和治疗方面取得了很大进步,但化疗仍然是治疗晚期癌症的主要方法,多重耐药性以及严重不良反应导致大多数晚期患者预后不良。天然分子产物协同抗癌药物增强抗肿瘤效果是一种临床上有前途的策略。双氢青蒿素(dihydroartemisinin,DHA)作为青蒿素的主要活性代谢产物,具有较强的抗疟活性和抗肿瘤作用,其抗肿瘤机制主要是通过加速Fe^(2+)介导的细胞氧化损伤、诱导肿瘤细胞凋亡、停滞细胞周期、抑制肿瘤血管生成、逆转肿瘤细胞的多耐药性等发挥作用。本文主要对DHA的抗消化道肿瘤作用以及分子机制做一综述。

WT1多肽乳佐剂疫苗的免疫增强效应及其对急性髓系白血病抗肿瘤效应研究

目的 评价Wilm瘤基因1(Wilms’ tumor gene1, WT1)多肽联合AddaVax^(TM)乳佐剂疫苗的稳定性、安全性、免疫增强效应及其对急性髓系白血病抗肿瘤效应。方法 用MALDI-TOF-MS飞行时间质谱评价该佐剂疫苗中WT1多肽的稳定性;将C57BL/6雌性小鼠按照随机数字表法分成3组:PBS组、WT1组和WT1+AddaVax^(TM)组,使用免疫剂量为抗原50μg/只、佐剂50μg/只,按照第0、14、28天肌肉注射免疫程序进行免疫。用HE染色评价疫苗肌肉注射小鼠脏器组织毒性;用ELISA检测细胞因子水平;ELISpot检测脾细胞分泌IFN-γ细胞数量;流式细胞术检测疫苗促体外骨髓来源树突状细胞(bone marrow-derived dendritic cells, BMDCs)成熟和促淋巴细胞活化及H-2Db WT1四聚体检测特异性CD8+T细胞比例;用C1498-mWT1稳转细胞株构建小鼠白血病肿瘤模型后,评价其预防与治疗的抗肿瘤效应。结果 WT1多肽可在疫苗中稳定存在,对小鼠肌肉注射未发生明显的脏器组织变化;对小鼠肌肉注射WT1+AddaVax^(TM)疫苗后,与WT1组相比,WT1+AddaVax^(TM)组可诱导高水平的Th1细胞免疫应答γ干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)及其Th17免疫应答白介素17A(IL-17A)(P<0.05);与WT1组相比,WT1+AddaVax^(TM)组促进脾淋巴细胞分泌IFN-γ的细胞数量增加(P<0.01),促进BMDCs成熟的标志物CD40^(+)/CD11c^(+)、CD86^(+)CD80^(+)/CD11c^(+)细胞比例增加(P<0.05),促进淋巴细胞中CD4^(+)/CD3^(+)T、CD69^(+)/CD8^(+)T细胞比例增加(P<0.05)及其特异性CD8+T细胞比例增加(P<0.05);利用C1498-mWT1小鼠急性髓系白血病皮下荷瘤模型的抗肿瘤效应中,WT1+AddaVax^(TM)组中位生存期相比于WT1组小鼠延长了6 d。在第50天时,WT1多肽+AddaVax^(TM)组小鼠生存率为28.5%,其他组小鼠全部死亡(P<0.05)。结论 WT1多肽联合AddaVax^(TM)乳佐剂疫苗具有良好的免疫学和明显抗肿瘤效果。

盐酸安罗替尼联合多西他赛对肺癌大鼠血小板凝聚、EGFR-STAT3信号通路及抑瘤作用研究

目的探究盐酸安罗替尼联合多西他赛对肺癌大鼠血小板凝聚、EGFR-STAT3信号通路及抑瘤作用。方法选取清洁级雄性Wistar大鼠50只,分为健康组、模型组、盐酸安罗替尼组、多西他赛组、联合组,平均10只/组,除健康组外其余均建立肺癌模型,建模后健康组与模型组大鼠采用等量生理盐水灌胃干预,多西他赛组在大鼠静脉注射多西他赛0.3mg/kg。盐酸安罗替尼组采用盐酸安罗替尼1.2 mg·kg^(-1)·d^(-1)灌胃干预,联合组予以静脉注射0.3mg·kg^(-1)·d^(-1)多西他赛注射液同时盐酸安罗替尼1.2 mg·kg^(-1)·d^(-1)灌胃,干预30d。采用血小板聚集凝血因子分析仪对血小板凝聚率进行检测,HE染色观察肺部病理变化,对比肿瘤体积变化,免疫印迹及PCR分别检测表皮生长因子受体(EGFR)、信号转导与转录激活因子3(STAT3)蛋白及mRNA。结果与健康组比较,模型组大鼠的血小板聚集率、肿瘤体积、肺组织中EGFR、STAT3蛋白及mRNA均显著升高(P<0.05);与模型组比较,盐酸安罗替尼组和多西他赛组血小板聚集率、肿瘤体积、肺组织中EGFR、STAT3蛋白及mRNA均显著降低(P<0.05);与盐酸安罗替尼组和多西他赛组比较,联合组血小板聚集率、肿瘤体积、肺组织中EGFR、STAT3蛋白及mRNA均显著降低(P<0.05)。结论盐酸安罗替尼联合多西他赛在肺癌的治疗中对改善血小板凝聚、调节EGFR-STAT3信号通路以及抑制肿瘤生长等方面均具有一定积极效用。

从“能散、能行”角度论辛味药的抗肿瘤作用

肿瘤是一种虚实夹杂的全身性疾病的局部体现,癥瘕积聚是其形成的主要原因之一。辛味药能够通过祛邪散寒、调节气机、活血化瘀等发挥消癥散结的作用,其活性成分可通过抑制肿瘤细胞的增殖和转移、诱导肿瘤细胞凋亡、调控多种信号通路、抑制肿瘤血管生成等多种机制起效。同时,辛味药配伍组方还可通过辛开苦降、辛甘化阳、辛散酸收、辛咸软坚等治法起到协同增效、缓解化疗副作用、调节机体免疫功能、降低不良反应发生率等作用。本文从“能散、能行”的角度,阐明辛味药可消除气滞、血瘀、痰凝、湿聚等肿瘤诱因,明晰了辛味药的抗肿瘤组方原理和配伍原则,为抗肿瘤中药的药性理论研究及临床上合理应用提供参考。

重楼复方抗肿瘤研究进展

中医常以扶正解毒法治疗癌症。清热解毒类中药重楼常与其他中药配伍进行抗肿瘤治疗。研究表明重楼复方可抑制肿瘤生长、侵袭及转移、逆转多药耐药、提高免疫水平、调节肠道菌群及癌细胞代谢发挥抗肿瘤作用。重楼复方在临床上已被应用于多种癌症的治疗。重楼复方可单独应用改善患者症状,也可通过联合化疗、放疗、常规治疗等提高治疗效果。

附子药理作用机制及减毒增效技术的研究进展

附子具有回阳救逆、补火助阳、温经散寒等功效,但对心脏、肝脏等多系统具有毒性作用,如何在保证疗效的同时降低毒性值得探究。目前,对附子的药理研究主要集中在其强心、保护血管、抗肿瘤、抗炎镇痛及保护神经系统等方面,并在不断挖掘新的方向,如调节免疫及改善糖尿病等。作用机制主要为通过多成分、多靶点、多途径地调控相关信号通路、离子通道等,在生物体内发生细胞水平、组织水平和系统水平的改善。对附子的减毒增效的研究主要是在炮制方法的革新和药物配伍的作用机制等方面。随着科技发展,无胆炮制、微生物发酵技术等逐渐推广应用,不仅能在降低附子毒性的同时维持甚至提升附子的药理作用,还研发出某些疾病的专属性炮制品,对附子的毒理及配伍后药物成分研究也有了长足发展。本文对附子近年来的药理作用及减毒增效的研究进展进行综述,并总结阐述了现有研究的不足之处,以期更好地利用附子资源。