高危型人乳头瘤病毒感染宫颈病变患者体质特点探析

目的探究高危型人乳头瘤病毒(HR-HPV)感染的宫颈病变患者中医体质分布特点,分析其临床特征与体质类型的关系,为中医药防治HR-HPV感染导致的宫颈病变提供依据。方法采用流行病学研究方法,以问卷调查的方式收集135例HR-HPV感染的宫颈病变患者相关信息,进行体质判定,分析其体质分布特点及主要体质类型与宫颈病变程度、HR-HPV感染特点、年龄及p16抑癌蛋白表达强度的关系。结果HR-HPV感染的宫颈病变患者体质类型所占比例由高到低依次为湿热质、阳虚质、平和质、气虚质、气郁质、阴虚质、痰湿质、血瘀质、特禀质,差异有统计学意义(P<0.05)。不同体质类型患者的宫颈病变程度、HR-HPV感染特点、年龄、p16抑癌蛋白表达强度比较,差异有统计学意义(P<0.05)。结论HR-HPV感染的宫颈病变患者体质类型以湿热质、阳虚质为主,其体质类型与宫颈病变程度、HR-HPV感染特点、年龄、p16抑癌蛋白表达强度有关。     

Anti-tumor activities of active ingredients in Compound Kushen Injection

Kushen (Radix Sophorae Flavescentis) has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling (Rhizoma Smilacis Glabrae). The main principles of CKI are matrine (MT) and oxymatrine (OMT) that exhibit a variety of pharmacological activities, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrotic and cardiovascular protective effects. Recent evidence shows that these compounds also produce anti-cancer actions, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- and/or radiotherapy-induced toxicity when combined with chemotherapeutic drugs. In this review, we summarize recent progress in studying the anti-cancer activities of MT, OMT and CKI and their potential molecular targets, which provide clues and references for further study.     

木鳖子抗肿瘤有效作用部位筛选及作用机制探讨

目的:观察中药木鳖子不同提取部位体内体外的抗肿瘤作用,并考察其中抗肿瘤效果显著的木鳖子乙酸乙酯提取部位的抗肿瘤作用机制。方法:采用索氏提取技术将中药木鳖子按照溶剂极性顺序依次提取,得到不同成分,采用细胞增殖实验结合动物抗肿瘤模型方法进行药效评价,运用现代分子生物学技术阐明其中最优部位可能的抗肿瘤作用机制。结果:中药木鳖子乙酸乙酯提取部位在体外和体内实验中均可表现出明显的抑制肿瘤生长能力(P0.05),且对实验动物无明显的毒副作用,本研究首次发现木鳖子乙酸乙酯提取部位可影响表皮生长因子(EGFR)激酶活性(P0.05),并可明显抑制EGFR蛋白磷酸化表达(P0.05),可明显抑制丝裂原活化蛋白激酶家族(mitogen activated protein kinase,MAPKs)通路上重要节点蛋白细胞外信号调节激酶(extracellular regulated protein kinases,ERK1/2),氨基末端激酶(C-Jun N-terminal kinase,JNK)和丝裂原激活蛋白激酶p38的磷酸化水平(P0.05),且具有浓度依赖关系。结论:中药木鳖子乙酸乙酯提取部位可通过抑制EGFR蛋白及相关通路蛋白活性,在体内外实验中显著抑制肿瘤的生长。     

Structures of Phytosterols and Triterpenoids with Potential Anti-Cancer Activity in Bran of Black Non-Glutinous Rice

Structures of some bioactive phytochemicals in bran extract of the black rice cv. Riceberry that had demonstrated anti-cancer activity in leukemic cell line were investigated. After saponification with potassium hydroxide, separation of the unsaponified fraction by reversed-phase high performance liquid chromatography (HPLC) resulted in four sub-fractions that had a certain degree of anti-proliferation against a mouse leukemic cell line (WEHI-3 cell), this being IC₅₀ at 24 h ranging between 2.80–467.11 μg/mL. Further purification of the bioactive substances contained in these four sub-fractions was performed by normal-phase HPLC. Structural characterization by gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance spectroscopy (NMR) resulted in, overall, the structures of seven phytosterols and four triterpenoids. Four phytosterols, 24-methylene-ergosta-5-en-3β-ol, 24-methylene-ergosta-7-en-3β-ol, fucosterol, and gramisterol, along with three triterpenoids, cycloeucalenol, lupenone, and lupeol, were found in the two sub-fractions that showed strong anti-leukemic cell proliferation (IC₅₀ = 2.80 and 32.89 μg/mL). The other sterols and triterpenoids were campesterol, stigmasterol, β-sitosterol and 24-methylenecycloartanol. Together with the data from in vitro biological analysis, we suggest that gramisterol is a significant anti-cancer lead compound in Riceberry bran extract.     

深海放线菌Micrococcus sp. R21的次生代谢产物研究

研究一株来源于西太平洋深海沉积环境(-6 310 m)的放线菌菌株Micrococcus sp. R21的抗肿瘤活性次生代谢产物。结合运用用硅胶, 凝胶柱色谱等方法从其菌液的乙酸乙酯萃取物中分离鉴定了8个化合物, 通过核磁数据结合其他波谱数据鉴定其结构分别为:环(4-羟基-L-脯-L-亮)二肽(1), 及环(L-脯-L-甘)二肽(2), 环(L-脯-L-丙)二肽(3), 环(D-脯-L-亮)二肽(4), N-β-乙酰色胺酸(5),邻羟基苯甲酸(6), 2-苯基乙酸(7)。其中化合物 1 对小鼠单核巨噬细胞白血病细胞RAW264.7显示出较好的生长抑制活性(IC₅₀=9.1 μmol·L^-1), 提示 1 可能是该菌抗肿瘤的活性成分。     

Recombinant human alpha fetoprotein synergistically potentiates the anti-cancer effects of 1′-S-1′-acetoxychavicol acetate when used as a complex against human tumours harbouring AFP-receptors

Purpose

Previous in vitro and in vivo studies have reported that 1′-S-1′-acetoxychavicol acetate (ACA) isolated from rhizomes of the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) induces apoptosis-mediated cell death in tumour cells via dysregulation of the NF-κB pathway. However there were some clinical development drawbacks such as poor in vivo solubility, depreciation of biological activity upon exposure to an aqueous environment and non-specific targeting of tumour cells. In the present study, all the problems above were addressed using the novel drug complex formulation involving recombinant human alpha fetoprotein (rhAFP) and ACA.

Experimental Design

To study the synergistic effect of both agents on human cancer xenografts, athymic nude (Nu/Nu) mice were used and treated with various combination regimes intraperitoneally. Serum levels of tumour markers for carcinoembryonic antigen (CEA) and prostate specific antigen (PSA) were assessed using sandwich ELISA. IHC and Western blotting were also conducted on in vivo tumour biopsies to investigate the involvement of NF-κB regulated genes and inflammatory biomarkers. Quantification and correlation between drug efficacies and AFP-receptors were done using IF-IC and Pearson''s correlation analysis.

Results

Mice exposed to combined treatments displayed higher reductions in tumour volume compared to stand alone agents, consistent with in vitro cytotoxicity assays. Milder signs of systemic toxicity, such as loss in body weight and inflammation of vital organs were also demonstrated compared to stand alone treatments. Tumour marker levels were consistent within all rhAFP/ACA treatment groups where levels of CEA and PSA were initially elevated upon commencement of treatment, and consecutively reduced corresponding to a decrease in tumour bulk volume. Both IHC and Western blotting results indicated that the combined action of rhAFP/ACA was not only able to down-regulate NF-κB activation, but also reduce the expression of NF-κB regulated genes and inflammatory biomarkers. The efficacy of rhAFP/ACA complex was also found to be weakly negatively correlated to the level of surface AFP-receptors between tumour types.

Conclusions

This drug complex formulation shows great therapeutic potential against AFP-receptor positive tumours, and serves as a basis to overcome insoluble and non-specific anti-neoplastic molecules.     

靶向性抗肺癌新药ZP-1在不同溶液中的稳定性研究

目的研究靶向性抗肺癌新药ZP-1在不同溶液中的稳定性,为ZP-1的深入研究提供理论依据。方法将ZP-1分别溶解于0.9%(质量浓度,下同)注射用生理盐水、无菌注射用水、5%(质量浓度,下同)葡萄糖注射液中,采用高效液相色谱法检测以上溶液中ZP-1的质量分数变化,以及不同温度下和光照条件下的质量分数变化。结果 ZP-1溶于0.9%注射用生理盐水中,分别于15、25、30℃条件下放置24 h,质量分数分别为99.22%、100.15%、98.96%,稳定性良好;ZP-1在无菌注射用水和5%葡萄糖注射液中稳定性不好,放置24 h相对质量分数分别下降为62.40%、68.61%。结论靶向性抗肺癌新药ZP-1在0.9%注射用生理盐水中具有良好的稳定性。     

Saporin-S6: A Useful Tool in Cancer Therapy

Thirty years ago, the type 1 ribosome-inactivating protein (RIP) saporin-S6 (also known as saporin) was isolated from Saponaria officinalis L. seeds. Since then, the properties and mechanisms of action of saporin-S6 have been well characterized, and it has been widely employed in the construction of conjugates and immunotoxins for different purposes. These immunotoxins have shown many interesting results when used in cancer therapy, particularly in hematological tumors. The high enzymatic activity, stability and resistance to conjugation procedures and blood proteases make saporin-S6 a very useful tool in cancer therapy. High efficacy has been reported in clinical trials with saporin-S6-containing immunotoxins, at dosages that induced only mild and transient side effects, which were mainly fever, myalgias, hepatotoxicity, thrombocytopenia and vascular leak syndrome. Moreover, saporin-S6 triggers multiple cell death pathways, rendering impossible the selection of RIP-resistant mutants. In this review, some aspects of saporin-S6, such as the chemico-physical characteristics, the structural properties, its endocytosis, its intracellular routing and the pathogenetic mechanisms of the cell damage, are reported. In addition, the recent progress and developments of saporin-S6-containing immunotoxins in cancer immunotherapy are summarized, including in vitro and in vivo pre-clinical studies and clinical trials.     

The anti-cancer effect of Huaier aqueous extract with rh-Endostatin and DDP

Objective： The aim of our study was to explore the inhibition and apoptosis-inducing effect of the combination of Huaier aqueous extract with recombinant human Endostatin and DDP in human lung adenocarcinoma A549 cells. We also investigated the reversal effect of Huaier aqueous extract in reversing cisplatin resistance in human lung adenocarcinoma A549/DDP cells. Methods： We treated A549 cells with Huaier aqueous extract and the combination of Huaier aqueous ex- tract and DDP or rh-Endostatin for 24 h, 36 h and 48 h. And then we calculated the inhibition rate through MTT approach and detected the apoptosis rate by flow cytometry. We also treated A549 and A549/DDP cells with DDP, Huaier aqueous extract, DDP and Huaier aqueous extract for 72 h, respectively. Results： Huaier aqueous extract can inhibit the growth of A549 cells and the inhibition rate improved with the increase of the concentration. The inhibition rate of the combination of rh-Endostatin and 4 mg/mL of Huaier aqueous extract in three time points and the combination of rh-Endostatin and 2 mg/mL of Huaier aqueous extract in the time point of 48 h on the growth of A549 cells all improved （P 〈 0.005）. The inhibition rate of the com- bination of DDP and Huaier aqueous extract with the concentration of 2 mg/mL or 4 mg/mL on the growth of A549 cells all improved （P 〈 0.005）. The combination of Huaier aqueous extract and DDP and the combination of Huaier aqueous extract with rh-Endostatin and DDP can improve the inhibition on the growth ofA549 cells （P 〈 0.005）. Conclusion： Huaier aqueous extract has the inhibition and apoptosis-inducing effects on the A549 cells. And the combination of Huaier aqueous extract and rh-Endostatin or DDP has the synergistic effects on the inhibition of A549 cells. The combination of Huaier aqueous extract with rh-Endostatin and DDP has the synergistic effects on the inhibition ofA549 cells. Huaier aqueous extract can reverse the cisplatin resistance in human lung adenocarcinoma A549/DDP cells.     

Medicinal plants commonly used against cancer in traditional medicine formulae in Sri Lanka

Cancer is a global burden. In low- and middle-income countries around 70% of deaths are due to cancer. For a number of years natural products have been a good source of agents for combatting cancer and plants have played a huge role in anti-cancer product development. For many centuries, indigenous cultures around the world have used traditional herbal medicine to treat a myriad of diseases including cancer. In Sri Lanka, a number of plants have been reported to have anti-cancer properties and some of the commonly used plants are described in this review with an account of their compounds and modes of action. Only a small number of the plants in Sri Lanka have been tested for their bioactivity and more research is required to determine their medicinal activity with the aim of developing novel drugs to fight this disease.