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Pesquisa : B01.650.940.800.575.912.250.884.916.500 [Categoria DeCS]
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[PMID]:29237435
[Au] Autor:Thronicke A; Steele ML; Grah C; Matthes B; Schad F
[Ad] Endereço:Forschungsinstitut Havelhöhe gGmbH, Kladower Damm 221, 14089, Berlin, Germany.
[Ti] Título:Clinical safety of combined therapy of immune checkpoint inhibitors and Viscum album L. therapy in patients with advanced or metastatic cancer.
[So] Source:BMC Complement Altern Med;17(1):534, 2017 Dec 13.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Despite improvement of tumour response rates in patients with progressive and metastatic cancer, immune checkpoint inhibitors (ICM) induce toxicities in cancer patients. Viscum album L. (VA, mistletoe) extracts are applied as add-on cancer therapy especially in German speaking countries and within integrative and anthroposophical concepts with the goal to improve quality of life. The primary objective of this pilot observational cohort study was to determine the rate of adverse events (AE) related to ICM therapy with and without VA in patients with advanced or metastatic cancer in a certified Cancer Center. METHODS: ICM or combined ICM/VA therapies were applied in patients with progressive or metastatic cancer. AE rates of both therapy groups were compared. RESULTS: A total of sixteen cancer patients were treated with ICM: nivolumab (75%), ipilimumab (19%) or pembrolizumab (6%). The median age of the study population was 64 years (IQR 57.8; 69.3); 44% were male. Of the sixteen patients receiving ICM, nine patients received additional VA (56%; ICM/VA group) and seven did not (44%; ICM group). No statistically significant differences were seen between groups with respect to AE-rates (67% ICM/VA versus 71% ICM). Adjusted multivariate regression analysis revealed that concomitant application of VA did not alter the AE rate in ICM treated patients. 85% of AEs were expected ICM reactions. No AEs of grade 3 or greater were documented for the total study cohort. CONCLUSIONS: This is the first study evaluating the clinical safety profile of ICM in combination with VA in patients with advanced or metastatic cancer. The overall AE rate of the study cohort is comparable to AE rates of ICM treatment in the literature. Our data indicate a first impression that concomitant VA application may not alter ICM-induced AE rates. However, the nature of this study does not allow excluding possible immunological interactions between ICM and VA. Further prospective trials in larger study cohorts should focus on the assessment of safety aspects, clinical efficacy and health related quality of life in patients with combined ICM/VA therapy. TRIAL REGISTRATION: DRKS00013335 , retrospectively registered (November 27th, 2017) at the German Clinical Trials Register ( www.drks.de ).
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Neoplasias/tratamento farmacológico
Extratos Vegetais/uso terapêutico
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Viscum album
[Mh] Termos MeSH secundário: Idoso
Antineoplásicos/efeitos adversos
Feminino
Interações Ervas-Drogas/imunologia
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Neoplasias/epidemiologia
Projetos Piloto
Extratos Vegetais/efeitos adversos
Receptor de Morte Celular Programada 1/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Plant Extracts); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-2045-0


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[PMID]:28719632
[Au] Autor:Steinborn C; Klemd AM; Sanchez-Campillo AS; Rieger S; Scheffen M; Sauer B; Garcia-Käufer M; Urech K; Follo M; Ücker A; Kienle GS; Huber R; Gründemann C
[Ad] Endereço:Center for Complementary Medicine, Institute for Infection Prevention and Hospital Epidemiology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
[Ti] Título:Viscum album neutralizes tumor-induced immunosuppression in a human in vitro cell model.
[So] Source:PLoS One;12(7):e0181553, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI) on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays. Furthermore, we examined whether VAEI was able to counteract tumor-induced immunosuppression within this cellular system using a renal cancer cell model. The role of mistletoe lectin (ML) was analyzed using ML-specific antibodies and ML-depleted VAEI. VAEI and VAEA augmented the maturation of dendritic cells. VAEI abrogated tumor-induced immunosuppression of dendritic cells and both processes were partially mediated by ML since ML-depleted VAEI and ML-specific antibodies almost neutralized the rehabilitative effects of VAEI on DC maturation. Using these settings, co-culture experiments with purified CD4+ T cells had no influence on T cell proliferation and activation but did have an impact on IFN-γ secretion. The study provides a potential mode-of-action of VAE as an additive cancer therapy based on immunomodulatory effects. However, the impact on the in vivo situation has to be evaluated in further studies.
[Mh] Termos MeSH primário: Tolerância Imunológica/efeitos dos fármacos
Extratos Vegetais/farmacologia
Viscum album/química
[Mh] Termos MeSH secundário: Adulto
Linfócitos T CD4-Positivos/efeitos dos fármacos
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD4-Positivos/secreção
Linhagem Celular Tumoral
Células Dendríticas/efeitos dos fármacos
Células Dendríticas/imunologia
Seres Humanos
Interferon gama/secreção
Lectinas/metabolismo
Linfócitos T/efeitos dos fármacos
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lectins); 0 (Plant Extracts); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171119
[Lr] Data última revisão:
171119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181553


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[PMID]:28222679
[Au] Autor:Skippington E; Barkman TJ; Rice DW; Palmer JD
[Ad] Endereço:Department of Biology, Indiana University, Bloomington, IN, 47405, USA.
[Ti] Título:Comparative mitogenomics indicates respiratory competence in parasitic Viscum despite loss of complex I and extreme sequence divergence, and reveals horizontal gene transfer and remarkable variation in genome size.
[So] Source:BMC Plant Biol;17(1):49, 2017 Feb 21.
[Is] ISSN:1471-2229
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Aerobically respiring eukaryotes usually contain four respiratory-chain complexes (complexes I-IV) and an ATP synthase (complex V). In several lineages of aerobic microbial eukaryotes, complex I has been lost, with an alternative, nuclear-encoded NADH dehydrogenase shown in certain cases to bypass complex I and oxidize NADH without proton translocation. The first loss of complex I in any multicellular eukaryote was recently reported in two studies; one sequenced the complete mitogenome of the hemiparasitic aerial mistletoe, Viscum scurruloideum, and the other sequenced the V. album mitogenome. The V. scurruloideum study reported no significant additional loss of mitochondrial genes or genetic function, but the V. album study postulated that mitochondrial genes encoding all ribosomal RNAs and proteins of all respiratory complexes are either absent or pseudogenes, thus raising questions as to whether the mitogenome and oxidative respiration are functional in this plant. RESULTS: To determine whether these opposing conclusions about the two Viscum mitogenomes reflect a greater degree of reductive/degenerative evolution in V. album or instead result from interpretative and analytical differences, we reannotated and reanalyzed the V. album mitogenome and compared it with the V. scurruloideum mitogenome. We find that the two genomes share a complete complement of mitochondrial rRNA genes and a typical complement of genes encoding respiratory complexes II-V. Most Viscum mitochondrial protein genes exhibit very high levels of divergence yet are evolving under purifying, albeit relaxed selection. We discover two cases of horizontal gene transfer in V. album and show that the two Viscum mitogenomes differ by 8.6-fold in size (66 kb in V. scurruloideum; 565 kb in V. album). CONCLUSIONS: Viscum mitogenomes are extraordinary compared to other plant mitogenomes in terms of their wide size range, high rates of synonymous substitutions, degree of relaxed selection, and unprecedented loss of respiratory complex I. However, contrary to the initial conclusions regarding V. album, both Viscum mitogenomes possess conventional sets of rRNA and, excepting complex I, respiratory genes. Both plants should therefore be able to carry out aerobic respiration. Moreover, with respect to size, the V. scurruloideum mitogenome has experienced a greater level of reductive evolution.
[Mh] Termos MeSH primário: Complexo I de Transporte de Elétrons/genética
Evolução Molecular
Transferência Genética Horizontal
Variação Genética
Genoma de Planta
Viscum/genética
[Mh] Termos MeSH secundário: DNA de Plantas
Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética
Complexo I de Transporte de Elétrons/metabolismo
Deleção de Genes
Genes de Plantas
Genoma Mitocondrial
Anotação de Sequência Molecular
Proteínas de Plantas/genética
RNA de Plantas
RNA Ribossômico
Análise de Sequência de DNA
Especificidade da Espécie
Viscum/metabolismo
Viscum album/genética
Viscum album/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Plant); 0 (Electron Transport Chain Complex Proteins); 0 (Plant Proteins); 0 (RNA, Plant); 0 (RNA, Ribosomal); EC 1.6.5.3 (Electron Transport Complex I)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170223
[St] Status:MEDLINE
[do] DOI:10.1186/s12870-017-0992-8


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[PMID]:28109285
[Au] Autor:Jeong J; Park CH; Kim I; Kim YH; Yoon JM; Kim KS; Kim JB
[Ad] Endereço:School of Life Science, Handong Global University, Pohang, 37544, Korea.
[Ti] Título:Korean mistletoe (Viscum album coloratum) extract regulates gene expression related to muscle atrophy and muscle hypertrophy.
[So] Source:BMC Complement Altern Med;17(1):68, 2017 Jan 21.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Korean mistletoe (Viscum album coloratum) is a semi-parasitic plant that grows on various trees and has a diverse range of effects on biological functions, being implicated in having anti-tumor, immunostimulatory, anti-diabetic, and anti-obesity properties. Recently, we also reported that Korean mistletoe extract (KME) improves endurance exercise in mice, suggesting its beneficial roles in enhancing the capacity of skeletal muscle. METHODS: We examined the expression pattern of several genes concerned with muscle physiology in C2C12 myotubes cells to identify whether KME inhibits muscle atrophy or promotes muscle hypertrophy. We also investigated these effects of KME in denervated mice model. RESULTS: Interestingly, KME induced the mRNA expression of SREBP-1c, PGC-1α, and GLUT4, known positive regulators of muscle hypertrophy, in C2C12 cells. On the contrary, KME reduced the expression of Atrogin-1, which is directly involved in the induction of muscle atrophy. In animal models, KME mitigated the decrease of muscle weight in denervated mice. The expression of Atrogin-1 was also diminished in those mice. Moreover, KME enhanced the grip strength and muscle weight in long-term feeding mice. CONCLUSIONS: Our results suggest that KME has beneficial effects on muscle atrophy and muscle hypertrophy.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/efeitos dos fármacos
Músculo Esquelético/efeitos dos fármacos
Extratos Vegetais/farmacologia
Viscum album/química
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Hipertrofia/tratamento farmacológico
Hipertrofia/genética
Masculino
Camundongos
Camundongos Endogâmicos ICR
Contração Muscular/efeitos dos fármacos
Denervação Muscular
Proteínas Musculares/genética
Músculo Esquelético/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
República da Coreia
Proteínas Ligases SKP Culina F-Box/genética
Transdução de Sinais/efeitos dos fármacos
Serina-Treonina Quinases TOR/metabolismo
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Muscle Proteins); 0 (Plant Extracts); EC 2.3.2.27 (Fbxo32 protein, mouse); EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.1.1 (mTOR protein, mouse); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170123
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-1575-9


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[PMID]:28101577
[Au] Autor:Schötterl S; Hübner M; Armento A; Veninga V; Wirsik NM; Bernatz S; Lentzen H; Mittelbronn M; Naumann U
[Ad] Endereço:Molecular Neuro-Oncology, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, D-72076 Tübingen, Germany.
[Ti] Título:Viscumins functionally modulate cell motility-associated gene expression.
[So] Source:Int J Oncol;50(2):684-696, 2017 Feb.
[Is] ISSN:1791-2423
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:In Europe extracts from Viscum album L., the European white-berry mistletoe, are widely used as a complementary cancer therapy. Viscumins (mistletoe lectins, ML) have been scrutinized as important active components of mistletoe and exhibit a variety of anticancer effects such as stimulation of the immune system, induction of cytotoxicity, reduction of tumor cell motility as well as changes in the expression of genes associated with cancer development and progression. By microarray expression analysis, quantitative RT-PCR and RT-PCR based validation of microarray data we demonstrate for the Viscum album extract Iscador Qu and for the lectins Aviscumine and ML-1 that in glioma cells these drugs differentially modulate the expression of genes involved in the regulation of cell migration and invasion, including processes modulating cell architecture and cell adhesion. A variety of differentially expressed genes in ML treated cells are associated with the transforming growth factor (TGF)-ß signaling pathway or are targets of TGF-ß. ML treatment downregulated the expression of TGF-ß itself, of the TGF-ß receptor II (TGFBR2), of the TGF-ß intracellular signal transducer protein SMAD2, and of matrix-metalloproteinases (MMP) MMP-2 and MMP-14. Even if the changes in gene expression differ between Aviscumine, Iscador Qu and ML-1, the overall regulation of motility associated gene expression by all drugs showed functional effects since tumor cell motility was reduced in a ML-dependent manner. Therefore, ML containing compounds might provide clinical benefit as adjuvant therapeutics in the treatment of patients with invasively growing tumors such as glioblastomas.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/genética
Expressão Gênica/efeitos dos fármacos
Glioblastoma/genética
Proteínas Inativadoras de Ribossomos Tipo 2/farmacologia
Toxinas Biológicas/farmacologia
Fator de Crescimento Transformador beta/genética
[Mh] Termos MeSH secundário: Neoplasias Encefálicas/tratamento farmacológico
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Perfilação da Expressão Gênica/métodos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Glioblastoma/tratamento farmacológico
Seres Humanos
Invasividade Neoplásica
Análise de Sequência com Séries de Oligonucleotídeos/métodos
Extratos Vegetais/farmacologia
Transdução de Sinais
Viscum album/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Extracts); 0 (Ribosome Inactivating Proteins, Type 2); 0 (Toxins, Biological); 0 (Transforming Growth Factor beta); 0 (mistletoe lectin I)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170502
[Lr] Data última revisão:
170502
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170120
[St] Status:MEDLINE
[do] DOI:10.3892/ijo.2017.3838


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[PMID]:28061770
[Au] Autor:Kleinsimon S; Kauczor G; Jaeger S; Eggert A; Seifert G; Delebinski C
[Ad] Endereço:Department of Pediatric Oncology/Hematology, Otto-Heubner-Centre for Pediatric and Adolescent Medicine (OHC), Charitém, Universitätsmedizin, Augustenburger Platz 1, 13353, Berlin, Germany.
[Ti] Título:ViscumTT induces apoptosis and alters IAP expression in osteosarcoma in vitro and has synergistic action when combined with different chemotherapeutic drugs.
[So] Source:BMC Complement Altern Med;17(1):26, 2017 Jan 07.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Osteosarcoma is the most common bone tumor and is associated with a poor prognosis. Conventional therapies, surgery and chemotherapy, are still the standard but soon reach their limits. New therapeutic approaches are therefore needed. Conventional aqueous mistletoe extracts from the European mistletoe (Viscum album L.) are used in complementary cancer treatment. These commercial extracts are water-based and do not include water-insoluble compounds such as triterpenic acids. However, both hydrophilic and hydrophobic triterpenic acids possess anti-cancer properties. In this study, a whole mistletoe extract viscumTT re-created by combining an aqueous extract (viscum) and a triterpene extract (TT) was tested for its anti-cancer potential in osteosarcoma. METHODS: Two osteosarcoma cell lines were treated with three different mistletoe extracts viscum, TT and viscumTT to compare their apoptotic potential. For this purpose, annexin/PI staining and caspase-3, -8 and -9 activity were investigated by flow cytometry. To determine the mechanism of action, alterations in expression of inhibitors of apoptosis (IAPs) were detected by western blot. Apoptosis induction by co-treatment of viscum, TT and viscumTT with doxorubicin, etoposide and ifosfamide was examined by flow cytometry. RESULTS: In vitro as well as ex vivo, the whole mistletoe extract viscumTT led to strong inhibition of proliferation and synergistic apoptosis induction in osteosarcoma cells. In the investigations of mechanism of action, inhibitors of apoptosis such as XIAP, BIRC5 and CLSPN showed a clear down-regulation after viscumTT treatment. In addition, co-treatment with doxorubicin, etoposide and ifosfamide further enhanced apoptosis induction, also synergistically. CONCLUSION: ViscumTT treatment results in synergistic apoptosis induction in osteosarcoma cells in vitro and ex vivo. Additionally, conventional standard chemotherapeutic drugs such as doxorubicin, etoposide and ifosfamide were able to dramatically enhance apoptosis induction. These results promise a high potential of viscumTT as an additional adjuvant therapy approach for osteosarcoma.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Apoptose/efeitos dos fármacos
Proteínas Inibidoras de Apoptose/genética
Osteossarcoma/tratamento farmacológico
Extratos Vegetais/administração & dosagem
Triterpenos/administração & dosagem
Viscum album/química
[Mh] Termos MeSH secundário: Proliferação Celular/efeitos dos fármacos
Criança
Doxorrubicina/administração & dosagem
Sinergismo Farmacológico
Quimioterapia Combinada
Etoposídeo/administração & dosagem
Seres Humanos
Proteínas Inibidoras de Apoptose/metabolismo
Masculino
Osteossarcoma/genética
Osteossarcoma/metabolismo
Osteossarcoma/fisiopatologia
Células Tumorais Cultivadas
Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética
Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (BIRC5 protein, human); 0 (Inhibitor of Apoptosis Proteins); 0 (Plant Extracts); 0 (Triterpenes); 0 (X-Linked Inhibitor of Apoptosis Protein); 0 (XIAP protein, human); 6PLQ3CP4P3 (Etoposide); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170108
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-016-1545-7


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[PMID]:27593449
[Au] Autor:Wójciak-Kosior M; Sowa I; Pucek K; Szymczak G; Kocjan R; Luchowski P
[Ad] Endereço:a Department of Analytical Chemistry , Medical University of Lublin , Lublin , Poland.
[Ti] Título:Evaluation of seasonal changes of triterpenic acid contents in Viscum album from different host trees.
[So] Source:Pharm Biol;55(1):1-4, 2017 Dec.
[Is] ISSN:1744-5116
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:CONTEXT: Viscum album L. (Loranthaceae) is a semi-parasitic plant used in pharmacy and medicine mostly for its hypotensive and anticancer activity. The effects may be related to the presence of triterpenic acids, such as betulinic (BA) and oleanolic (OA) acids. OBJECTIVES: In our investigations the content of triterpenic acids in V. album from different host trees depending on the season of harvest was determined. MATERIAL AND METHODS: V. album herb was dried and extracted with ethyl acetate using ultrasound energy. The reversed phase HPLC-PDA method was used for the analysis of triterpenic acids. The structure of the target components was confirmed by mass spectrometry with an electrospray ionization source. RESULTS: Diversity in the content of both compounds was noted; however, OA was the dominant triterpenic acid and the amount thereof was ∼10 times higher than that of BA. The analysis of changes in the amount of triterpenic acids during the spring-winter period revealed the highest content of OA in summer (from 6.84 to 13.65 mg/g). In turn, in the other seasons of harvest, the content was in the range of 4.41-9.83, 6.41-9.56 and 5.59-12.16 mg/g for spring, autumn and winter, respectively. In most cases, a similar tendency was observed for BA. DISCUSSION AND CONCLUSION: In most cases, the highest amount of the investigated compounds was found in summer; thus, this period seems to be optimal for acquisition of plant material rich in triterpenic acids.
[Mh] Termos MeSH primário: Ácido Oleanólico/metabolismo
Estações do Ano
Árvores/parasitologia
Triterpenos/metabolismo
Viscum album/metabolismo
[Mh] Termos MeSH secundário: Acetatos/química
Cromatografia Líquida de Alta Pressão
Reprodutibilidade dos Testes
Solventes
Espectrometria de Massas por Ionização por Electrospray
Fatores de Tempo
Ultrassom
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetates); 0 (Solvents); 0 (Triterpenes); 4G6A18707N (betulinic acid); 6SMK8R7TGJ (Oleanolic Acid); 76845O8NMZ (ethyl acetate)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170309
[Lr] Data última revisão:
170309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160906
[St] Status:MEDLINE


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[PMID]:27589063
[Au] Autor:Twardziok M; Kleinsimon S; Rolff J; Jäger S; Eggert A; Seifert G; Delebinski CI
[Ad] Endereço:Department of Pediatric Oncology/Hematology, Otto Heubner Centre for Pediatric and Adolescent Medicine (OHC), Charité, Universitätsmedizin Berlin, Germany.
[Ti] Título:Multiple Active Compounds from Viscum album L. Synergistically Converge to Promote Apoptosis in Ewing Sarcoma.
[So] Source:PLoS One;11(9):e0159749, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ewing sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10-15% of relapses. Hydrophobic triterpene acids and hydrophilic lectins and viscotoxins from European mistletoe (Viscum album L.) demonstrate anticancer properties, but have not yet been investigated for Ewing sarcoma. Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We recreated a total mistletoe effect by combining an aqueous extract (viscum) and a triterpene extract (TT) solubilized with cyclodextrins. Ewing sarcoma cells were treated with viscum, TT and viscumTT in vitro, ex vivo and in vivo. In vitro and ex vivo treatment of Ewing sarcoma cells with viscum inhibited proliferation and induced apoptosis in a dose-dependent fashion, while viscumTT combination treatment generated a synergistic effect. Apoptosis occurred via intrinsic and extrinsic apoptotic pathways, evidenced by activation of both CASP8 and CASP9. We show that viscumTT treatment shifts the balance of apoptotic regulatory proteins towards apoptosis, mainly via CLSPN, MCL1, BIRC5 and XIAP downregulation. ViscumTT also demonstrated strong antitumor activity in a cell line- and patient-derived mouse model, and may be considered an adjuvant therapy option for pediatric patients with Ewing sarcoma.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/farmacologia
Apoptose/efeitos dos fármacos
Neoplasias Ósseas/tratamento farmacológico
Extratos Vegetais/farmacologia
Sarcoma de Ewing/tratamento farmacológico
Viscum album
[Mh] Termos MeSH secundário: Animais
Antineoplásicos Fitogênicos/uso terapêutico
Neoplasias Ósseas/metabolismo
Neoplasias Ósseas/patologia
Caspase 8/metabolismo
Caspase 9/metabolismo
Linhagem Celular Tumoral
Relação Dose-Resposta a Droga
Feminino
Xenoenxertos
Seres Humanos
Camundongos
Fitoterapia/métodos
Extratos Vegetais/uso terapêutico
Sarcoma de Ewing/metabolismo
Sarcoma de Ewing/patologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Plant Extracts); EC 3.4.22.- (Caspase 8); EC 3.4.22.- (Caspase 9)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160903
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0159749


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[PMID]:27491866
[Au] Autor:Weissenstein U; Kunz M; Urech K; Regueiro U; Baumgartner S
[Ad] Endereço:Iscador AG, Arlesheim, Switzerland. u.weissenstein@hiscia.ch.
[Ti] Título:Interaction of a standardized mistletoe (Viscum album) preparation with antitumor effects of Trastuzumab in vitro.
[So] Source:BMC Complement Altern Med;16:271, 2016 Aug 04.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Besides conventional anticancer therapy many breast cancer patients use complementary and alternative medicine (CAM) like the medicinal herb mistletoe (Viscum album L.). To gain more knowledge about possible herb-drug interactions between CAM and conventional anticancer medications, in the present in vitro study we investigated the effect of a standardized mistletoe preparation on the action of Trastuzumab, a drug used for the treatment of Her-2 positive breast cancer. METHODS: The Her-2 positive human breast carcinoma cell line SK-BR-3 was treated with Trastuzumab. Different doses of the drug were combined with Viscum album extract (VAE) in clinically relevant doses. Proliferation, apoptosis, cell cycle and the secretion of vascular endothelial growth factor (VEGF) were analyzed. RESULTS: No inhibition of antitumor efficacy of Trastuzumab by VAE was detected. VAE and Trastuzumab, either alone or in combination, inhibited proliferation of SK-BR-3 cells in vitro. At higher concentrations VAE induced apoptosis, which was not observed for Trastuzumab. Cells treated with Trastuzumab underwent a G0/G1 cell cycle arrest and cells treated with VAE a G2/M arrest. After application of the two drugs in combination both G0/G1 and G2/M arrest was observed. VEGF secretion of SK-BR-3 cells was significantly inhibited by sole treatment with Trastuzumab or VAE. Combined treatment of Trastuzumab and VAE at clinically relevant doses showed additive inhibitory effects on VEGF secretion. CONCLUSIONS: VAE did not interfere with cytostatic effects of Trastuzumab on SK-BR-3 cells in vitro. Our in vitro results suggest that no risk of safety by herb drug interactions has to be expected from the exposition of cancer cells to Trastuzumab and VAE simultaneously. In contrast, VAE and Trastuzumab seem to exhibit complementary anti-cancer effects in vitro.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/farmacologia
Extratos Vegetais/farmacologia
Trastuzumab/farmacologia
Viscum album/química
[Mh] Termos MeSH secundário: Antineoplásicos Fitogênicos/química
Apoptose/efeitos dos fármacos
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Seres Humanos
Extratos Vegetais/química
Trastuzumab/química
Fator A de Crescimento do Endotélio Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Plant Extracts); 0 (Vascular Endothelial Growth Factor A); P188ANX8CK (Trastuzumab)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160806
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-016-1246-2


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[PMID]:27485618
[Au] Autor:Axtner J; Steele M; Kröz M; Spahn G; Matthes H; Schad F
[Ad] Endereço:Forschungsinstitut Havelhöhe gGmbH, Kladower Damm 221, 14089, Berlin, Germany.
[Ti] Título:Health services research of integrative oncology in palliative care of patients with advanced pancreatic cancer.
[So] Source:BMC Cancer;16:579, 2016 08 02.
[Is] ISSN:1471-2407
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Pancreatic cancer has a dire prognosis and is associated with a high mortality. Palliative patients have special needs and often seek help in integrative oncological concepts (IO) that combine conventional and complementary therapies. Nevertheless there are few recommendations regarding IO in current cancer guidelines. The aims of this study were to report on implementation of IO in everyday palliative care and to analyze patient survival in advanced pancreatic cancer. METHODS: This multicenter observational study investigates the implementation of IO and length of survival of patients suffering from advanced pancreatic cancer (stage IV). We analyzed patient's survival by employing multivariable proportional hazard models using different parametric distribution functions and compared patients receiving chemotherapy only, a combination of chemotherapy and Viscum album (VA) treatment, and VA treatment only. RESULTS: Records of 240 patients were analyzed. Complementary therapy showed high acceptance (93 %). Most frequent therapy was VA treatment (74 %) that was often administered concomitantly to chemotherapy (64 %). Both therapies had positive effects on patient survival as they had significant negative effects on the hazard in our log-normal model. A second analysis showed that patients with combined chemotherapy and VA therapy performed significantly better than patients receiving only chemotherapy (12.1 to 7.3 month). Patients receiving only VA therapy showed longer survival than those receiving neither chemotherapy nor VA therapy (5.4 to 2.5 months). Our data demonstrates that IO can be implemented in the everyday care of patients without disregarding conventional treatment. Patients combining VA with chemotherapy showed longest survival. CONCLUSIONS: Our data demonstrate the importance and potential of health services research showing that IO treatment can be successfully implemented in the every-day care of patients suffering from advanced pancreatic cancer. Patients combining VA with chemotherapy showed longest survival. To address patients' needs adequately, future cancer guidelines might increasingly include comments on complementary treatment options in addition to conventional therapies. Further studies should investigate the effect of complementary treatments on survival and quality of life in more detail.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Pesquisa sobre Serviços de Saúde/métodos
Cuidados Paliativos/métodos
Neoplasias Pancreáticas/tratamento farmacológico
Extratos Vegetais/administração & dosagem
Viscum album/química
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/uso terapêutico
Terapia Combinada
Terapias Complementares
Tratamento Farmacológico
Feminino
Seres Humanos
Masculino
Neoplasias Pancreáticas/patologia
Extratos Vegetais/uso terapêutico
Modelos de Riscos Proporcionais
Qualidade de Vida
Análise de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Plant Extracts)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160804
[St] Status:MEDLINE
[do] DOI:10.1186/s12885-016-2594-5



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