Long-term survival of a patient with advanced pancreatic cancer under adjunct treatment with Viscum album extracts: A case report

BACKGROUND Advanced pancreatic cancer(aPC) has a poor prognosis with limited survival benefit from current standard treatment. Viscum album extracts(VAE) are used by many cancer patients, showing immune-stimulating effects, improved quality of life, and a survival benefit in patients with aPC.CASE SUMMARY A 59-year-old architect developed epigastric pain. A cystic lesion of the pancreas of 45-mm diameter was detected. In a follow-up magnetic resonance imaging,about one year later, multiple lesions were seen in the corpus and the tail of the pancreas; CA-19-9 was elevated to 58.5 U/mL. A distal pancreatectomy with splenectomy was performed, and a tumor of 7 cm × 5 cm × 3.5 cm was excised.Histologic investigation showed an intraductal papillary mucinous neoplasmassociated invasive adenocarcinoma with invasion of the lymph vessels,perineural invasion, and positive nodes(2/27); surgical margins showed tumor cells, and the tumor was classified as pT3 N1 M0 R1. The patient was treated with radiation of the tumor bed and capecitabine/oxaliplatin followed by gemcitabine and FOLFIRINOX. Seven months after surgery, a liver metastasis was detected and treatment with FOLFIRINOX was started. Four months after detection of the metastasis, the patient opted for additional treatment with VAE. Another month later, the metastasis was treated with radiofrequency ablation(RFA). Eight months later, the hepatic lesion recurred and was again treated with RFA. Thecontinuous VAE treatment was increased in dose, and the patient stayed recurrence-free for the next 39 mo in good health and working full-time(as of the time this case report was written).CONCLUSION We present the case of a patient with aPC with R1-resection with development of liver metastasis during the course of treatment who showed an overall survival of 63 mo and a relapse-free survival of 39 mo under increasing VAE therapy. The possible synergistic effect on tumor control of RFA treatment and immunestimulatory effects of VAE should be further investigated.

Staging of Adrenal Gland and Pancreas Neoplastic Cystwith Ultradiluted Viscum album:Case Report

Many animal adrenal lesions are frequently observed at necropsy and most often are asymptomatic with clinical syndromes that cause hypofunction or hyperfunction of the gland.The objective of this report is to demonstrate the staging of cysts and to report the clinical evolution of the dog that presented pathognomonic lesions of Cushing's Syndrome and developed Adrenal Cyst and a mass in the Pancreas.We concluded that the use of ultradiluted Viscum album in this patient promoted the control and staging of cystic tumor disease,pruritus and improved immunity to date,totaling 22 months of injectable therapy.

Viscum Album Modulates Apoptotic Related Genes in Melanoma Tumor of Mice

Cancer is a major public health problem throughout the world. It is estimated that one third of the American population will develop the disease at some time during their lifetimes. Among these, melanoma will account for 7% of the cases. In Brazil, in 2012, it is estimated that over six thousand new melanoma cases occurred. During recent years, the incidence of melanoma has increased, mainly due to a more constant exposure of the skin to sunlight. In this work, our aim is to assess the expression of apoptotis-related genes melanoma tumors in mice treated with Viscum album (VA). This will allow us to better understand the molecular mechanisms underlying tumor cell death activation caused by this compound. Our results clearly demonstrate upregulation of pro apoptotic genes (Trp53bp2, Nol3, Fadd, Tnfsf10, Traf1, Traf2, Cflar, Card10, Nod1, Casp 2, Casp7, Xiap, Dad1, and Dffb). Further bioinformatics-based tool analysis allowed us to assess which specific cell death-related intracellular pathways were activated by VA treatment. Two major effects of VA in melanoma cells could be observed: generation of an immunomudulatory Th-1 like action, recruiting several interleukines, and cell death activation through Caspase7, associated uspstream with Card10 and downstream with CAD. In summary, VA modulates apoptosis related genes in cancer melanoma cells. Although a deeper study should be conducted, VA seems to interfere with important signaling pathways within melanoma cells that control the cellular mechanisms of apoptosis activation. Therapeutic approaches using VA as an antineoplastic and adjuvant medication compounding should be considered.

Proximate and mineral components of Viscum album var. coloratum grown on eight different host tree species

Mistletoes are parasite plants growing on various tree species,taking nutrients from the host.Beneficial compounds of mistletoe were used in medicine and these mistletoes were commonly collected from oak species that were not well identified.We analyzed the nutritional value by measuring proximate and mineral components of Korean mistletoe(Viscum album var.coloratum)from various host trees.Carbohydrate was the most proximate component in both leaves and twigs followed crude protein,crude fiber,crude ash and crude fat.While the contents of the proximate components and minerals varied among hosts and between plant parts,leaves contained higher crude protein and ash,and more minerals except for magnesium than twigs,although no significant difference was found inmistletoe grown on Prunus mandshurica.There were significant differences of proximate and mineral contents depending on the host species.Mistletoe grown on Chaenomeles sinensis contained higher levels of carbohydrates,crude fat,crude ash,magnesium,calcium,sodium,iron,and zinc than mistletoe grown on other species.Mistletoe grown on P.mandshurica contained high mineral levels of potassium,copper and phosphorous.The nutritional value of mistletoes were greatly influenced by the host species but among the hosts,specific nutrients accumulated in leaves more than in twigs,and vice versa.Based on the analysis,Korean mistletoe contains relatively good quality of nutrients and has high potential for dietary supplements as well as for medicinal compounds.

Mild Steel Corrosion Mitigation in Sulphuric Acid via Benign Isolated Phytochemicals from <I>Viscum album</I>

We present the evaluation of four Eco-friendly corrosion inhibitors for the corrosion mitigation of mild steel in acid media. The corrosion inhibition of mild steel by ethanol extracts from Viscum album (EEVA) and some of its isolated phytochemical components;phytates extract (PEVA), saponins extract (SEVA), and flavonoids extracts (FEVA) have been studied using gravi-metric and gasometric techniques. The results of the study reveal that these ecofriendly and benign extracts function as good inhibitors for mild steel corrosion in sulphuric acid. Inhibition efficiency of the extracts increases with inhibitor concentration and temperature rise. The trend of inhibition efficiency in lower inhibitor concentration is EEVA > PEVA > SEVA > FEVA and at higher concentration, the order was SEVA > PEVA > EEVA > FEVA. The presence of the plant extracts decreases the corrosion activation energy in the solution which indicates chemical adsorption mechanism. The adsorption of the components of the extracts is consistent with Temkin isotherm. The interaction between the isolated extracts is synergistic at lower inhibitor concentration and antagonistic at higher concentrations. The Kads values for PEVA and SEVA are higher than those of EEVA and FEVA. This implies that PEVA and SEVA are more efficiently adsorbed on the mild steel surface.

Renoprotective and Blood Pressure Lowering Impact of Equisetum arvense and Viscum album Therapy in Experimental Model of Chronic Kidney Disease

Background: Chronic kidney disease (CKD) is an irreversible decline in the glomerular filtration due to nephrosclerosis and glomerular loss. Rat remnant kidney model enables to assess the benefits of different treatment possibilities. Aim: The aim of our study was to investigate renal morphology and functioning after 12 weeks of treatment with Equisetum arvense and Viscum album. Methods: Male Wistar rats with 5/6 nephrectomy received herbal drug preparation Equisetum/Viscum in a dosage of 0.007 g/kg/die (herbal group) or losartan (180 mg/l, ARB group) or remained untreated. Systolic blood pressure (SBP) and proteinuria were measured. Renal cortex tissue samples examined for focal-segmental glomerulosclerosis (FSGS) and interstitial fibrosis (IF). mRNA was isolated to estimate CCL2/MCP-1 gene transcription. Results: SBP was significantly lower both in herbal group and ARB group compared with untreated animals (p between ARB group and untreated NPX (p = 0.001). Quantitative RT-PCR analysis revealed statistically significant differences of mRNA transcription for MCP-1 between herbal group and untreated group (p Conclusions: We report about beneficial impact of horsetail Equisetum arvense and mistletoe Viscum album treatment on kidney functioning and morphology.

Three new bioactive flavonoid glycosides from Viscum album

Two new flavonoid glycosides, named viscumneoside XⅡ(1), and viscumneoside XⅢ(2);a new dihydrogen flavonoid glycoside product named viscumneoside XⅣ(3), were isolated from the aerial part of Viscum album, along with seven known compounds(4-10). Their structures were identified by analysis of spectroscopic data. In addition, cytotoxicity assay showed that 1, 2 and 3 possessed significant inhibitory activities against C6, A549 and MDA-MB-231(the inhibition rate arrived about 50%, 70% and74% respectively with IC50 ≤ 60.00 μmol·L^-1), while the inhibition of TF-1 and Hela was not significant.

Two symmetrical unsaturated acids isolated from Viscum album

In the present study,two new acetylene conjugate compounds,dibutyl(2Z,6Z)-octa-2,6-dien-4-yne dioate(1),and dibutyl(2E,6E)-octa-2,6-dien-4-yne dioate(2),were isolated from the dry stem leaves of Viscum album,along with nine known compounds(3–11).Their structures were confirmed on the basis of spectroscopic data.Compounds 1 and 8 showed antioxidant activity against xanthine oxidase(XOD)and 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydroxyl(DPPH),with the IC_(50) of 1.22 and 1.33μmol·L^(–1),and the SC_(50 )of 4.34 and 8.22μmol·L^(–1),respectively.

新外来中药白果槲寄生的中药药性探讨

白果槲寄生是桑寄生科槲寄生属白果槲寄生(Viscum album L.)的新鲜带叶茎枝和果实,中国无分布。在欧洲被广泛应用于癌症的治疗,被列入《美国顺势疗法药典》《德国顺势疗法药典》等。目前,以白果槲寄生提取物为主要原料的海利升注射液已作为进口的天然药物进入我国临床,主要用于肺癌、乳腺癌、卵巢癌辅助治疗。通过总结分析白果槲寄生科学研究文献,结合中医理论对其中药药性进行探讨。通过对白果槲寄生的活性成分、临床应用、药理作用等文献分类研究,归纳出白果槲寄生具有抗癌和提高癌症患者生命质量、降血糖、降血压、抗氧化、抗癫痫等药理作用;依据临床应用和使用情况,结合中药药性理论,经过综合分析研究赋予了白果槲寄生中药药性。白果槲寄生的性味归经为性平味甘;归肝、肾、脾经。功效为解毒散结、平肝潜阳、益气养阴,可用于治疗癥瘕积聚,肝阳上亢,痫证,津伤口渴,内热消渴等。供配制成药用(皮下注射),建议从1 mL 0.000 1 mg开始,每周注射次数根据患者情况决定。

槲寄生总碱和多糖对黄曲霉菌毒素诱发大鼠肝癌前病变时血清同工酶含量的影响

目的研究槲寄生提取物对黄曲霉毒素B1(AFB1)诱发大鼠肝癌前病变时同工酶含量的影响。方法60只大鼠被分为正常对照组、单纯肝大部切除组、AFB1模型组、槲寄生总碱组和槲寄生多糖组。后3组大鼠一次性ip给予AFB10.75mg·kg-1,第3周起饲以含0.015%二乙酰氨基芴饲料5周。后4组大鼠于第3周末施行肝大部切除术。槲寄生总碱和槲寄生多糖组于肝大部切除术后1周开始分别ig给予槲寄生总碱8g·kg-1和槲寄生多糖6g·kg-1,每天1次,连续给药4周。第8周末处死大鼠,采用组织化学染色法检测肝组织切片中γ-谷氨酰转肽酶(GGT)阳性染色面积;免疫吸附法测定血清GGT同工酶Ⅱ(GGTⅡ)阳性表达;酶速率法和琼脂糖电泳法测定血清乳酸脱氢酶(LDH)和碱性磷酸酶(ALP)总活性及其同工酶相对含量。结果AFB1引起肝脏组织中GGT表达明显增加;大鼠血清GGTⅡ阳性率明显升高;血清LDH总活性和LDH5含量增高,且LDH5>LDH4;血清ALP1含量明显升高,并出现异常ALP电泳条带。大鼠ig给予槲寄生总碱或槲寄生多糖治疗4周,肝脏组织中GGT表达明显减少,血清GGTⅡ阳性率明显下降,血清LDH总活力、LDH5和ALP1含量均较模型组明显降低。结论AFB1诱发的大鼠肝癌前病变有多种同工酶的表达异常,槲寄生总碱和多糖可能通过调节同工酶的表达干预肝癌前病变的发生和发展。

球形红细菌生物转化槲寄生中总黄酮类化合物的测定

目的建立槲寄生及球形红细菌转化槲寄生培养液中总黄酮类化合物的含量测定方法，并对各个样品的含量进行比较研究。方法采用紫外分光光度法，以芦丁为对照品，以亚硝酸钠一硝酸铝溶液为显色系统．512nm波长处测定总黄酮类化合物的含量。结果芦丁在8-48μg／ml的范围内线性关系良好，回归方程为l，=10．627X-0．0544，r=O．9979。槲寄生75％的乙醇提取物（样品3）、水提取物（样品6）经过球形红细菌转化总黄酮类化合物的含量分别增加129％、65％。结论经过球形红细菌转化可以增加槲寄生提取液中总黄酮类化合物的含量。

Mechanisms involved in Korean mistletoe lectin-induced apoptosis of cancer cells

AIM： To investigate the anti-cancer mechanisms of Korean mistletoe lectin （Viscum album coloratura agglutinin, VCA） using a human colon cancer cell line （COLO）. METHODS： Cytotoxic effects of VCA on COLO cells were determined by 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （MTI-） assay in vitro and tumor-killing effects in vivo. To study the mechanisms involved, the expression of various pro-caspases, anti- apoptotic proteins, and death receptors was determined by western blot. To determine which death receptor is involved in VCA-induced apoptosis of COLO cells, cytotoxicity was examined by MTT assay after treatment with agonists or antagonists of death receptors. RESULTS： VCA killed COLO cells in a time- and dosedependent manner and induced complete regression of tumors in nude mice transplanted with COLO cells. Treatment of COLO cells with VCA activated caspase-2, -3, -8, and -9 and decreased expression of anti-apoptotic molecules including receptor interacting protein, nuclear factor-κB, X-linked inhibitor of apoptosis protein, and Akt/protein kinase B. We then examined the involvement of death receptors in VCA-induced apoptosis. Only tumor necrosis factor receptor 1, among the death receptors examined, was involved in apoptosis of COLO cells, evidenced by inhibition of VCA-induced apoptosis and decreased activation of caspases, particularly caspase-8, by tumor necrosis factor receptor 1 antagonizing antibody.CONCLUSION： VCA-induced apoptotic COLO cell death is due to the activation of caspases and inhibition of antiapoptotic proteins, in part through the tumor necrosis factor receptor 1 signaling pathway.

Factors shaping community structure of endophytic fungi–evidence from the Pinus-Viscum-system

Endophytic fungal communities have been shown to be highly diverse in almost every host plant species analyzed so far.However,the factors shaping their compositions are largely unknown.To elucidate the impact of various factors,10 independent replicates of DNA extracts from each of 17 surface-sterilized leaf and stem samples were analyzed by pyrosequencing of fungal ITS1 rRNA gene amplicons.Altogether,154 fungal OTUs(operational taxonomic units),represented by 953,385 sequences,were found in at least 2 samples from Viscum album ssp.austriacum and/or its host Pinus sylvestris.Deviating from earlier,cultivation-based assessments,the communities were dominated by OTUs related to the genus Mortierella and OTUs not assignable to a certain fungal phylum.However,Ascomycota were still the most diverse group in terms of OTU richness and already hypothesized organ and host preferences of certain endophytic Xylariaceae isolated from the Pinus-Viscum-system could be confirmed.Host species and organ type were also the major factors shaping the detected fungal communities.The two plant species clearly differed according to the endophytic fungal communities,but only stems and needles of Pinus were inhabited by significantly different fungal assemblages.Interestingly,only the 1 and 3 year old stem sections differed according to the endophytic fungal community,while differently aged leaves of both plants were indistinguishable in this regard.Size of the organs had no impact on fungal communities in Pinus,but shorter internodes and smaller leaves showed at least a tendency to differ from the corresponding larger organs in Viscum.Fungal communities also differed slightly between the two sampling sites,lying 200 km apart,and between the three sampling campaigns.Because the samples were drawn within 15 days,this finding indicates that seasonal shifts clearly outweigh aging effects in host plant with perennial leaves.The results therefore provide strong evidence against a linear development of the endophytic fungal communities in Pinus sylvestris and Viscum album over the years.The communities seem to establish themselves already in the year the respective organs emerge.Further study is required to clarify whether they predominantly establish anew each year,or if the core community persists throughout subsequent years.The most abundant endophytic OTUs are known from soil and/or dead plant material and are supposed to represent latent decomposers.The study reveals for the first time that host and/or organ preferences of putatively saprotrophic fungi are predominantly responsible for compositional differences in the endophytic fungal communities between host plants and organs.While the analyses are shown to provide rather robust results,the significance of genetic abundance,as revealed by high-throughput sequencing analyses,remains an unsettled issue.This is discussed in detail,as well as the challenges in assigning taxonomic names to OTUs.

家族性圆柱瘤过表达对槲寄生凝集素诱导HCT116细胞凋亡的影响

目的:探讨家族性圆柱瘤(CYLD)过表达对槲寄生凝集素诱导人大肠癌HCT116细胞凋亡的影响。方法:MTT法测定细胞的增殖活力,琼脂糖凝胶电泳观察细胞凋亡,流式细胞仪进行细胞周期分析,蛋白质印迹实验和地高辛标记的凝胶电泳阻滞试验(DIG-EMSA)研究细胞凋亡途径。结果:CYLD过表达不影响肠癌HCT116细胞株的生长,但可抑制NF-κB的活性,可增强槲寄生凝集素对HCT116细胞的生长抑制作用,尤其作用12h后CYLD转染细胞细胞的抑制较HCT116细胞和空质粒转染对照细胞更为明显(P<0.01),但不影响槲寄生凝集素对NF-κB的抑制作用,也不影响槲寄生凝集素对IκBα、Bcl-2和Bax的表达。结论:CYLD过表达可抑制NF-κB的活性,并增强槲寄生凝集素对HCT116细胞的生长抑制作用,提示其调控细胞的功能可能取决于NF-κB在细胞中的作用。