Thomas Efferth

..We estimate these results will be a further step toward the ultimate goal of individualized, patient-adapted tumor treatment based on tumor molecular profiling...

..The effects of rituximab on antioxidant genes represent a novel mechanism of rituximab for chemosensitization...

..Oxidative stress-resistant thymic lymphoma-derived WEHI7.2 variants are also more resistant to cantharidin. These data suggest that cantharidin treatment causes oxidative stress that provokes DNA damage and p53-dependent apoptosis...

..ART acts via p53-dependent and- independent pathways in isogenic p53+/+ p21WAF1/CIP1+/+, p53-/- p21WAF1/CIP1+/+, and p53+/+ p21WAF1/CIP1-/- colon carcinoma cells...

..We found that p53 mutated cell lines were more resistant to L-alanosine than p53 wild type cell lines...

..Taken together these data support a role for oxidative stress in the mechanism of ART action in tumor cells and suggest that antioxidant defenses act in combination to affect the cellular response to ART...

..In conclusion, the combination treatment of ART and OSI-774 resulted in an increased growth inhibition of GBM cell lines as compared to each drug alone...

..The present investigation represents a starting point to dissect the genes and molecular pathways responsible for cellular response to cantharidin in more detail...

..This indicates that different sets of genes involved in oxidative stress response and metabolism may contribute to the cytotoxic and differing toxic side effects of these drug classes...

..The implementation of pharmacogenetics into clinical routine diagnostics including genotype-based recommendations for treatment decisions and risk assessment for practitioners represents a challenge for the future...

..The multi-factorial nature of cellular response to artemisinin and its derivatives may be beneficial to treat otherwise drug-resistant tumors and may explain why resistance development has not been observed in either cancer or malaria...

..GST expression in normal organs may, therefore, contribute to the good tolerability and minimal toxicity of ART in normal organs...

..Homo- or heterozygosity did not correlate to survival of patients in the Kaplan-Meier analysis. In conclusion, we do not have reason to assume that the C3435T SNP contributes to drug resistance of ALL and prognosis of ALL patients...

..The concept of individualized therapy aims to determine in vitro the drug response of tumors beforehand to choose effective treatment options for each individual patient...

..We conclude that c-Myc and Max-mediated transcriptional control of gene expression might contribute to the therapeutic effects of ART in cancer cells, but may also confer unwanted side effects by affecting therapy-unrelated genes...

..Furthermore, methotrexate-resistant cell lines clustered together. Our future efforts will be directed toward those imbalances which implicate still unknown candidate drug resistance genes...

..The present investigation presents a starting point to dissect the genes and molecular pathways involved in the tumor cells' response to CET and HHT in greater detail...

..By hierarchical cluster analyses, candidate genes were identified which significantly predicted sensitivity or resistance of cell lines to hellebrin...

..By COMPARE and hierarchical cluster analyses, candidate genes were identified, which significantly predicted sensitivity or resistance of cell lines to miltirone...

..This pointed to mitochondrial aconitase and ceruloplasmin (ferroxidase)...

..In conclusion, our data indicate that TCM-derived natural products are worth being further investigated as novel compounds to eradicate tumors which reveal resistance to established anti-cancer drugs...

..g. the translationally controlled tumor protein (TCTP). Emphasis is given to pharmacogenomic approaches to analyze the pleiotropic nature of mechanisms of artemisinins in cancer cells...

..It merits further investigation, whether ART is responsive in clinically refractory tumors and whether the genes identified in the present study also determine clinical responsiveness towards ART...

..An interference of these two pathways and NO is known for inflammation and auto-immune diseases. The therapeutic potential of this compound has to be explored in the future...

..We found that ascaridol exerts antineoplastic activity. The findings of the present investigation are the first hint that ascaridol may be an interesting novel candidate drug for cancer treatment...

..The activation of these signalling pathways might be explained by the fact that berberine intercalates DNA and induces DNA strand break through inhibition of topoisomerases and induction of DNA lesions...

..Pretherapeutical detection of 9p21 and MTAP deletion may be helpful in developing a predictive molecular chemosensitivity test for T-ALL...

..Another salient feature of these compounds is the lack of severe side effects in malaria patients...

..Multidrug resistance (MDR) hampers chemotherapy in head and neck squamous cell carcinoma (HNSCC). There is little information about MDR mediating drug transporters in HNSCC...

..The data suggest that various metastasis profiles exist...

..The cell cycle might be arrested by dicentrine-induced DNA lesions...

..The majority of anticancer drugs are of natural origin. However, it is unknown whether the medicinal plant Thymus vulgaris L. (thyme) is cytotoxic towards head and neck squamous cell carcinoma (HNSCC)...

..The present analysis is a starting point for the generation of hypotheses on candidate genes and for a more detailed dissection of the functional role of individual genes for the activity of Artesunate in tumor cells...

..Collateral sensitivity was observed for artesunic acid homodimer. Artesunic acid and artesunic acid homodimer induced G0/G1 cell cycle arrest, apoptosis, and formation of reactive oxygen species...

..Taken together, these data show that scillarenin is a potential novel candidate for P-glycoprotein inhibition at BBB, and, thereby, may improve the efficacy of therapy regimens in treating brain diseases...

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..The present analysis is a starting point for the generation of hypotheses on candidate genes and for a more detailed dissection of the functional role of individual genes for the activity of artemisinin derivatives in tumor cells...

..This could provide a new therapeutic option to treat cancer cells with mutations in NER genes...

..As a consequence, a significant sensitization of cells to cytostatic drugs was achieved. In conclusion, ABCA2 and ABCA3 are expressed in many T-ALL and contribute to drug resistance...

..CONCLUSIONS: The expression profile of these factors predicts a significantly better long-term outcome of NSCLC patients. This may have implications for the development of individualized therapy options in the future...

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..marginatum to validate some of its ethnopharmacologial uses...

..Multiple mechanisms may account for cytotoxicity of these camptothecins...

..These findings could explain the different biological behaviour and treatment response of these tumours...

..From a nutritional point of view, it is a thriving perspective to further investigate whether C. longa may be used as a spice to improve cancer therapy...

..Multidrug-resistant cells overexpressing the MDR1, MRP1 or BCRP genes were not cross-resistant to arsenic trioxide. Our approach revealed that response of tumor cells towards arsenic trioxide is multi-factorial...

..Moreover, we reported, for the first time, that the growth inhibitory effect of NS-398 is mediated by down-regulation of RRM2, CTGF, MCM2 and PCNA and up-regulation of NAG-1 in all cell lines...

..We conclude that our microarray-based approach is a feasible and effective tool in identifying prognostic markers for drug resistance in antitumor therapy...

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..We investigated the cytotoxic potential of essential oil from the leaves of a medicinal plant, Levisticum officinale (lovage) on head and neck squamous carcinoma cells (HNSCC)...

..First encouraging experience in the clinical treatment of patients suffering from uveal melanoma calls for comprehensive clinical trials with artesunate for cancer treatment in the near future...

..In addition, other signaling pathways also contribute to the inhibitory effect of artesunate towards RAW 264.7 cells pointing to a multi-factorial mode of action of artesunate...

..In addition to tubulin as primary target, microarray-based mRNA signatures of responsiveness of these compounds have been identified by COMPARE and signaling pathway profiling...

..The aim of this study was therefore to investigate the influence of all important anti-HIV drugs on BCRP activity in vitro in one assay to allow unrestricted comparison of the results...

..In the long term, natural products from TCM can contribute to the development of molecular target-guided therapies and individualized treatment strategies...

..Chemical compounds from natural sources provide a large variety of potential anti-HIV compounds. The most promising natural products are discussed in this review...

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..Kampo-derived natural products represent a valuable reservoir for individual tumour treatment strategies in the future...

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..The cytotoxic effects of resveratrol on healthy cells can be neglected, and, as several pathways leading to chemotherapeutic effects are activated by resveratrol, chemoresistance-inducing mutations in cancer cells can be overcome...

..Natural products need to be investigated in more detail to explore their potential as novel adjuncts to established HBV or HCV therapy...

..These results indicate that the cytostatic and apoptotic effects of artesunate are not diminished by concomitant immunosuppression...

..In conclusion, the most important question for recognition and implementation of TCM into WM concerns the clinical evidence for the efficacy of TCM and international quality standards for TCM products...

..Furthermore, the most promising and recently discovered natural products with anti-malarial potential will be introduced...

..Thus, the up-regulation of the proteins JUN, N-RAS, FOS, cyclin D and cdk4 predicts the growth of NSCLC in nude mice...

..Thus, artesunate possesses attractive antiviral characteristics which are suggestively based on the interference with essential steps in the host cell kinase cascades...

..Upon excitation by light, hypericin generates cytotoxic products rendering its use attractive as photosensitizing agent. In this review both PPD and PDT are explained in detail, with a particular focus on molecular mechanisms...

..A further L84F mutant might affect Zn2+ binding. W65C was found to possibly be unstable...

..The aim of the current study was to evaluate molecular and cellular effects of OSI-774, a novel EGFR tyrosine kinase inhibitor, on nine glioblastoma multiforme (GBM) cell lines...

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..The average number of CNAs per cell line was higher in the sensitive than in the resistant group (total 13.1:8.5; significant CNAs 9.1:5.8)...

..As the microarray allows the determination of the expression profile of many ABC transporters in a single hybridization experiment, it may be useful as a diagnostic tool to detect drug resistance in clinical samples...

..As a low-cost drug, it might be of particular interest for areas of Kaposi's sarcoma endemics. ART could be useful for the prevention of tumor angiogenesis...

..Aberrant RAG-mediated recombination may be responsible in T-ALL, and exuberant DNA repair by nonhomologous end-joining is the likely prevailing mechanism in SCCHN, but a distinct mechanism in TCC and glioma remains to be elucidated...

..Our study provides evidence that rViscumin is capable of enhancing cytotoxicity of anticancer agents in vitro. This synergism appears to be independent of transcriptional activity of DNA repair relevant genes...

..Eventually, each of the cell lines could be characterized by its specific pattern of genomic imbalance...

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..Its good tolerability and lack of serious side effects will facilitate prospective randomized trials in the near future...

..e. ganciclovir, cidofovir or foscarnet, was detected in HCMV-infected fibroblasts. These findings might open new perspectives regarding the use of ART in clinical trials...

..The data indicate that DSBs induced by artesunate are repaired by the HR and NHEJ pathways. They suggest that DNA damage induced by artesunate contributes to its therapeutic effect against cancer cells...

..The objective of the present work was to decipher the effect of CuNG on reactive oxygen species (ROS) generation and antioxidant enzymes in normal and doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox)-bearing Swiss albino mice...

..CONCLUSION: Our results show the potential usefulness of CuNG in immunotherapy of drug-resistant cancers irrespective of multidrug resistance phenotype...

..Multidrug resistance can be caused by ATP-binding cassette (ABC) transporters that function as drug efflux pumps. The majority of these proteins have not yet been examined in malignant diseases...

..These results suggest a potential usefulness of artemisinin in combination with current pharmacological therapy for the treatment of human and veterinary infections by flaviviruses...

..The time-kill curves of clove and rosemary essential oils towards three strains showed clearly bactericidal and fungicidal processes of (1)/(2) x MIC, MIC, MBC and 2 x MIC...

..This review emphasizes these transporters, their clinical relevance and the diagnostic methods and strategies to circumvent multidrug resistance (MDR) mediated by ABC transporters...

..Similarly, the apoptotic cell fractions, as measured by flow cytometry, were lower if IL-6 was added to the medium. These results indicate that IL-6 may contribute to drug resistance in multiple myeloma...

..Moreover, 7-xylosyl-10-deacetylpaclitaxel had no effect on the expression of CD95 and NF-kappaB proteins, indicating that apoptosis was induced through the mitochondrial-dependent pathway in PC-3 cells...

..1 to 29.7 microM...

..Medullary thyroid carcinoma (MTC) is a rare calcitonin-producing tumor, derived from the parafollicular C-cells of the thyroid. MTC is known to be relatively insensitive to conventional chemotherapy...

..0, 5.3, 10.2, and 12.3 microM, respectively...

..6 microM. In contrast to the standard cytostatic drugs doxorubicin, vincristine, and paclitaxel, CEM/ADR5000 cells therefore did not exhibit cross-resistance to scopoletin and isoscopoletin...

..The alkaloids (1-3) exhibited weak to moderate take in vitro inhibitory activity against HIV replication in C8166 cells, and they (as well as carbalexine A and B) had cytotoxic activity against the human leukaemia cell line CCRF-CEM...

..Moreover, artesunate in conjunction with lamivudine had synergic anti-HBV effects, which warrants further evaluation of artemisinin/artesunate as antiviral agents against HBV infection...

..In the calcein assay, these two quinolones were shown to be moderate modulators of p-gp activity. Evocarpine, on the other side, is not transported by p-gp, and showed only slight toxicity at the highest test concentration of 30 microM...