蒲公英内生真菌PG23抗癌活性的初步研究

研究药用植物蒲公英内生真菌PG23多糖对肺癌A549细胞的抑制作用。蒲公英内生真菌PG23通过培养,乙醇沉淀获得粗多糖、苯酚-硫酸法测定多糖含量,采用MTT法测定PG23多糖对肺癌A549细胞的抑制率,并计算半抑制浓度(IC50)。结果表明,PG23发酵液中多糖得率为2.754%,多糖含量为26.82%;对A549肺癌细胞的抑制率以第1天为最高;抑制率不与多糖浓度成比例,最佳作用浓度为14.42μg/mL,抑制率为87.63%(P<0.01),IC50为1.073mg/mL(24h)。PG23发酵液多糖对肺癌A549细胞具有较强的抑制能力。     

Preliminary evaluation of serial (18) FDG-PET/CT to assess response to toceranib phosphate therapy in canine cancer

Palladia(TM) (toceranib phosphate-Pfizer Animal Health) is a novel orally administered receptor tyrosine kinase inhibitor (TKI) approved for treatment of canine mast cell tumors. Receptor tyrosine kinase dysregulation leads to tumor growth, progression, and metastasis. Toceranib's targets include vascular endothelial growth factor receptor (VEGFR-2/Flk-1/KDR), platelet-derived growth factor receptor, and kit. Positron Emission Tomography/Computed Tomography (PET/CT) is used commonly to diagnose, prognosticate, and monitor response to antineoplastic therapy in human patients. In this study, serial PET/CT imaging with (18) F-fluorodeoxyglucose ((18) FDG) was used to assess response to toceranib therapy in dogs with measurable solid malignancies. Six tumor-bearing dogs underwent tumor assessment using both standard RECIST criteria and PET/CT prior to and at a median of 5 weeks postinitiation of toceranib treatment. Toceranib was prescribed initially at a target dose 3.25 mg/kg PO q48 h, with subsequent modifications based on observed toxicity. Treatment was continued in patients achieving stable disease with acceptable drug tolerance. One dog was maintained on drug despite dose modification due to toxicity; measurable clinical and image-based responses were seen after 10 weeks of therapy. All others had stable or progressive disease based on clinical restaging and PET/CT at first recheck. . Due to discordance with anatomic and metabolic imaging, further studies are needed to investigate the role of molecular imaging in assessment of drug response and identify other potential molecular targets of toceranib.     

血清可溶性细胞间粘附分子在大肠癌患者组织中的检测及其意义

目的:探讨血清可溶性细胞间粘附分子1(sICAM-1)的检测在大肠癌患者中的临床意义。方法:采用双抗体夹心ELISA法检测50例大肠癌、30例大肠良性病变及30例健康体检者血清sICAM-1水平,并比较大肠癌患者术前、术后,转移、无转移sICAM-1水平变化。结果:大肠癌患者血清sICAM-1水平明显高于良性病变患者及正常人(P<0.01);大肠癌患者术后血清sICAM-1水平较术前明显下降(P<0.01);有转移的大肠癌患者血清sICAM-1水平高于无转移的患者(P<0.01)。结论:血清sICAM-1水平与大肠癌的发生、发展密切相关,可作为大肠癌新的检测指标之一。     

双歧杆菌完整肽聚糖的体外抗肿瘤作用及对大鼠大肠肿瘤的影响

目的：观察双歧杆菌完整肽聚糖（WPG）体外抗肿瘤作用及对大鼠大肠肿瘤的影响。方法：采用MTT法检测双歧杆菌WPG对人结肠癌细胞株LS-174T、人胃粘膜上皮细胞株GES-1的杀伤作用。以二甲肼（DMH）为诱发荆,观察双歧杆菌WPG对大鼠大肠肿瘤的防治作用;DMH诱癌及双歧杆菌WPG灌胃时间为18周,在第33周结束实验。结果：双歧杆菌WPG在体外对人结肠癌细胞株具有显著的选择性杀伤作用,体内给药可明显降低大鼠大肠肿瘤发生率（60％vs100％,P〈0．01）．但大肠癌平均个数及肿瘤体积指数的差异无显著性（P〉0．05）。结论：双歧杆菌的WPG对DMH诱导的大鼠大肠肿瘤具有预防作用。     

Liposomal clodronate treatment for tumour macrophage depletion in dogs with soft‐tissue sarcoma

Increased numbers of tumour‐associated macrophages correlate with rapid tumour growth and metastasis in tumours. Thus, macrophage depletion has potential as a novel cancer therapy and positive responses have been reported in rodent tumour models. To investigate the effectiveness of this approach in dogs with cancer, we evaluated the effects of the macrophage‐depleting agent liposomal clodronate (LC) in dogs with soft‐tissue sarcoma (STS). To this end, we conducted a clinical trial of LC therapy in 13 dogs with STS. Repeated LC administration was well tolerated clinically. Preliminary examination of tumour biopsy sets from 5 of the 13 dogs demonstrated that the density of CD11b⁺ macrophages was significantly decreased after LC treatment. Circulating concentrations of interleukin‐8 were also significantly reduced. These preliminary studies are the first to suggest that LC can be used as a systemic macrophage‐depleting agent in dogs to reduce numbers of tumour‐associated macrophages.     

Benefits of Daily Intake Tea on Human Health

The recent research achievements about the mechanisms of beneficial health effects of tea polyphenols and the epidemiological investigation on anti-cancer,anti-cardiovascular diseases,and anti-obesity through tea consumption were reviewed.It is proved that reactive oxygen species is the main reason to induce cell mutation,DNA damage,obesity,high blood pressure and many kinds of cancers.Tea catechins and theaflavins have excellent bioactivity on scavenging ROS due to their characteristic structure feature of phenolic hydroxyl group,which means drinking tea could prevent diseases.Epidemidogical investigations also showed that tea consumption could reduce the risk of lung cancer,gastric cancer,bladder cancer,and so on.However,the frequency of tea drinking or tea consumption amounts significantly affected the prevention efficiency.The epidemiologic investigations also find that drink green tea,especial black tea is useful to modify the cardiovascular diseases.In vivo and vitro tests showed that tea supplement could moderate the metabolism of blood lipid and prevent obesity.These indicated that tea and tea extracts might reduce the risk of many diseases.     

The Marine Natural Product Manzamine A Targets Vacuolar ATPases and Inhibits Autophagy in Pancreatic Cancer Cells

Manzamine A, a member of the manzamine alkaloids, was originally isolated from marine sponges of the genus Haliclona. It was recently shown to have activity against pancreatic cancer cells, but the precise mechanism of action remained unclear. To further our understanding of the mechanism of action of manzamine A, chemogenomic profiling in the yeast S. cerevisiae was performed, suggesting that manzamine A is an uncoupler of vacuolar ATPases. Fluorescence microscopy confirmed this effect on yeast vacuoles, where manzamine A produced a phenotype very similar to that of the established v-ATPase inhibitor bafilomycin A1. In pancreatic cancer cells, 10 µM manzamine A affected vacuolar ATPase activity and significantly increased the level of autophagosome marker LC3-II and p62/SQSTM1 as observed by western blot analysis. Treatment with manzamine A in combination with bafilomycin A1 (inhibitor of autophagosome-lysosome fusion) did not change the levels of LC3-II when compared to cells treated with bafilomycin A1 alone, suggesting that manzamine A is a potential inhibitor of autophagy by preventing autophagosome turnover. As autophagy is essential for pancreatic tumor growth, blocking this pathway with manzamine A suggests a promising strategy for the treatment of pancreatic cancer.     

Bioactive Compounds from the Red Sea Marine Sponge Hyrtios Species

In continuation of our search for drug leads from Red Sea sponges we have investigated the ethyl acetate fraction of the organic extract of the Red Sea sponge Hyrtios species. Bioassay-directed fractionation of the active fraction resulted into the identification of three new alkaloids, hyrtioerectines D–F (1–3). Hyrtioerectines D–F belong to the rare marine alkaloids in which the indole and β-carboline fragments of the molecule are linked through C-3/C-3 of both moieties. The structures of the isolated compounds were established based on different spectroscopic data including UV, IR, 1D and 2D NMR (COSY, HSQC, and HMBC) and high-resolution mass spectral studies. The antimicrobial activity against several pathogens and the free radical scavenging activity of the compounds using DPPH reagent were evaluated. In addition, the growth inhibitory activity of the compounds against three cancer cell lines was also evaluated. Hyrtioerectines D–F (1–3) displayed variable antimicrobial, free radical scavenging and cancer growth inhibition activities. Generally, compounds 1 and 3 were more active than compound 2.     

Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines

Dicathais orbita is a large Australian marine gastropod known to produce bioactive compounds with anticancer properties. In this research, we used bioassay guided fractionation from the egg mass extract of D. orbita using flash column chromatography and identified fractions containing tyrindoleninone and 6-bromoisatin as the most active against colon cancer cells HT29 and Caco-2. Liquid chromatography coupled with mass spectrometry (LCMS) and ¹H NMR were used to characterize the purity and chemical composition of the isolated compounds. An MTT assay was used to determine effects on cell viability. Necrosis and apoptosis induction using caspase/LDH assay and flow cytometry (PI/Annexin-V) and cell cycle analysis were also investigated. Our results show that semi-purified 6-bromoisatin had the highest anti-cancer activity by inhibiting cell viability (IC₅₀ = ~100 µM) and increasing caspase 3/7 activity in both of the cell lines at low concentration. The fraction containing 6-bromoisatin induced 77.6% apoptosis and arrested 25.7% of the cells in G2/M phase of cell cycle in HT29 cells. Tyrindoleninone was less potent but significantly decreased the viability of HT29 cells at IC₅₀ = 390 µM and induced apoptosis at 195 µM by increasing caspase 3/7 activity in these cells. This research will facilitate the development of these molluscan natural products as novel complementary medicines for colorectal cancer.