SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "LAR1:uu ;pers:(Larsson Rolf);srt2:(2005-2009);pers:(Isaksson Anders);mspu:(article)"

Sökning: LAR1:uu > Larsson Rolf > (2005-2009) > Isaksson Anders > Tidskriftsartikel

  • Resultat 1-9 av 9
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Andersson, Claes R., et al. (författare)
  • In vitro drug sensitivity-gene expression correlations involve a tissue of origin dependency
  • 2007
  • Ingår i: Journal of chemical information and modeling. - 1549-9596. ; 47:1, s. 239-248
  • Tidskriftsartikel (refereegranskat)abstract
    • A major concern of chemogenomics is to associate drug activity with biological variables. Several reports have clustered cell line drug activity profiles as well as drug activity-gene expression correlation profiles and noted that the resulting groupings differ but still reflect mechanism of action. The present paper shows that these discrepancies can be viewed as a weighting of drug-drug distances, the weights depending on which cell lines the two drugs differ in.
  •  
2.
  • Fryknäs, Mårten, et al. (författare)
  • Phenotype-based screening of mechanistically annotated compounds in combination with gene expression and pathway analysis identifies candidate drug targets in a human squamous carcinoma cell model
  • 2006
  • Ingår i: Journal of Biomolecular Screening. - 1087-0571. ; 11:5, s. 457-468
  • Tidskriftsartikel (refereegranskat)abstract
    • The squamous cell carcinoma HeLa cell line and an epithelial cell line hTERT-RPE with a nonmalignant phenotype were interrogated for HeLa cell selectivity in response to 1267 annotated compounds representing 56 pharmacological classes. Selective cytotoxic activity was observed for 14 of these compounds dominated by cyclic adenosine monophosphate (cAMP) selective phosphodiesterase (PDE) inhibitors, which tended to span a representation of the chemical descriptor space of the library. The PDE inhibitors induced delayed cell death with features compatible with classical apoptosis. The PDE inhibitors were largely inactive when tested against a cell line panel consisting of hematological and nonsquamous epithelial phenotypes. In a genome-wide DNA microarray analysis, PDE3A and PDE2A were found to be significantly increased in HeLa cells compared to the other cell lines. The pathway analysis software PathwayAssist was subsequently used to extract a list of proteins and small molecules retrieved from Medline abstracts associated with the hit compounds. The resulting list consisted of major parts of the cAMP-protein kinase A pathway linking to ERK, P38, and AKT. This molecular network may provide a basis for further exploitation of novel candidate targets for the treatment of squamous cell carcinoma.
  •  
3.
  • Fryknäs, Mårten, et al. (författare)
  • STAT1 signaling is associated with acquired crossresistance to doxorubicin and radiation in myeloma cell lines
  • 2007
  • Ingår i: International Journal of Cancer. - 0020-7136. ; 120:1, s. 189-195
  • Tidskriftsartikel (refereegranskat)abstract
    • The myeloma cell line RPMI 8226/S and its doxorubicin resistant subline 8226/Dox40 were used as models to explore the potential importance of the STAT1 signaling pathway in drug and radiation resistance. The 40-fold doxorubicin resistant subline 8226/Dox40 was found to be crossresistant to single doses of 4 and 8 Gy of radiation. A genome-wide mRNA expression study comparing the 8226/Dox40 cell line to its parental line was performed to identify the underlying molecular mechanisms. Seventeen of the top 50 overexpressed genes have previously been implicated in the STAT1 signaling pathway. STAT1 was over expressed both at the mRNA and protein level. Moreover, analyses of nuclear extracts showed higher abundance of phosphorylated STAT1 (Tyr 701) in the resistant subline. Preexposure of the crossresistant cells to the STAT1 inhibiting drug fludarabine reduced expression of overexpressed genes and enhanced the effects of both doxorubicin and radiation. These results show that resistance to doxorubicin and radiation is associated with increased STAT1 signaling and can be modulated by fludarabine. The data support further development of therapies combining fludarabine and radiation.
  •  
4.
  • Hassan, Saadia, et al. (författare)
  • Gene expression signature-based chemcial genomics and activity pattern in a panel of tumour cell lines propose linalyl acetate as a protein kinase/NF-κB inhibitor
  • 2008
  • Ingår i: Gene Therapy and Molecular Biology. - 1529-9120. ; 12:B, s. 359-370
  • Tidskriftsartikel (refereegranskat)abstract
    • The essential oil of Lebanese sage, Salvia libanotica, was reported to have anti-tumour activity; however, the mechanism of action has not been identified yet. In this study, 14- cancer cell lines including drug-sensitive and resistant lung, leukaemia, and colon, as well as primary human tumours of chronic lymphocytic leukaemia (CLL) and primary normal mononuclear cells (PBMCs) were used to characterize the anti-tumour activity and mechanism of action of linalyl acetate, a component of the Lebanese sage essential oil. Drug activity and gene expression data sets were utilized to identify drugs with similar activity patterns and genes involved in drug sensitivity/resistance. In addition, the Connectivity Map, a gene expression signature-based screening approach, assisted in predicting further the molecular action of linalyl acetate. Small cell lung carcinoma and colorectal cancer cell lines were the most sensitive to the drug and greater tumour selectivity was observed against chronic lymphocytic leukaemia cells compared to normal mononuclear cells. Only limited effect of some of the classical mechanisms of multi-drug resistance on the activity of Linalyl acetate was noted which makes it potentially interesting for drug-resistant patients. There was high similarity between the activity-pattern/gene expression profile of linalyl acetate and that of protein kinase/NF-kappa B inhibitors. Validating this, linalyl acetate was found to strongly inhibit Janus kinase, JAK3, and p38 alpha kinases in a cell-free assay as well as the NF-kappa B translocation in a dose-dependent manner. Taken together, our results show that the NF-kappa B inhibitor, linalyl acetate, may represent a new therapeutic compound in the management of inflammation and cancer.
  •  
5.
  • Laryea, Daniel, et al. (författare)
  • Characterization of the cytotoxic activity of the indoloquinoline alkaloid cryptolepine in human tumour cell lines and primary cultures of tumour cells from patients
  • 2009
  • Ingår i: Investigational new drugs. - 0167-6997. ; 27:5, s. 402-411
  • Tidskriftsartikel (refereegranskat)abstract
    • The plant derived indoloquinoline alkaloid cryptolepine was investigated for its cytotoxic properties in 12 human tumour cell lines and in primary cultures of tumour cells from patients. The fluorometric microculture cytotoxicity assay was used to assess cytotoxicity and DNA micro-array analysis to evaluate gene expression. Cryptolepine mean IC(50) in the cell line panel was 0.9 muM compared with 1.0 and 2.8 muM in haematological and solid tumour malignancies, respectively. Among patient solid tumour samples, those from breast cancer were the most sensitive and essentially as sensitive as haematological malignancies. Cryptolepine activity showed highest correlations to topoisomerase II and microtubule targeting drugs. In the cell lines cryptolepine activity was essentially unaffected by established mechanisms of drug resistance. A number of genes were identified as associated with cryptolepine activity. In conclusion, cryptolepine shows interesting in vitro cytotoxic properties and its further evaluation as an anti-cancer drug seems warranted.
  •  
6.
  • Milani, Lili, et al. (författare)
  • Allelic imbalance in gene expression as a guide to cis-acting regulatory single nucleotide polymorphisms in cancer cells
  • 2007
  • Ingår i: Nucleic Acids Research. - 0305-1048. ; 35:5, s. e34
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the relative expression levels of two SNP alleles of a gene in the same sample is an effective approach for identifying cis-acting regulatory SNPs (rSNPs). In the current study, we established a process for systematic screening for cis-acting rSNPs using experimental detection of AI as an initial approach. We selected 160 expressed candidate genes that are involved in cancer and anticancer drug resistance for analysis of AI in a panel of cell lines that represent different types of cancers and have been well characterized for their response patterns against anticancer drugs. Of these genes, 60 contained heterozygous SNPs in their coding regions, and 41 of the genes displayed imbalanced expression of the two cSNP alleles. Genes that displayed AI were subjected to bioinformatics-assisted identification of rSNPs that alter the strength of transcription factor binding. rSNPs in 15 genes were subjected to electrophoretic mobility shift assay, and in eight of these genes (APC, BCL2, CCND2, MLH1, PARP1, SLIT2, YES1, XRCC1) we identified differential protein binding from a nuclear extract between the SNP alleles. The screening process allowed us to zoom in from 160 candidate genes to eight genes that may contain functional rSNPs in their promoter regions.
  •  
7.
  •  
8.
  • Rickardson, Linda, et al. (författare)
  • Screening of an annotated compound library for drug activity in a resistant myeloma cell line
  • 2006
  • Ingår i: Cancer Chemotherapy and Pharmacology. - 0344-5704. ; 58:6, s. 749-758
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Resistance to anticancer drugs is a major problem in chemotherapy. In order to identify drugs with selective cytotoxic activity in drug-resistant cancer cells, the annotated compound library LOPAC(1280), containing compounds from 56 pharmacological classes, was screened in the myeloma cell line RPMI 8226 and its doxorubicin-resistant subline 8226/Dox40. Methods: Cell survival was measured by the Fluorometric Microculture Cytotoxicity Assay. Results: Selective cytotoxic activity in 8226/Dox40 was obtained for 33 compounds, with the most pronounced difference observed for the glucocorticoids. A microarray analysis of the cells showed a difference in mRNA-expression for the glucocorticoid receptor suggesting potential mechanisms for the difference in glucocorticoid sensitivity. In the presence of the glucocorticoid-receptor antagonist RU486, the sensitivity to the glucocorticoids was reduced and a similar effect level in RPMI 8226 and 8226/Dox40 was achieved. Conclusion: In conclusion, screening of mechanistically annotated compounds on drug-resistant cancer cells can identify compounds with selective activity and provide a basis for the development of novel treatments of drug-resistant malignancies.
  •  
9.
  • Wickström, Malin, et al. (författare)
  • Pharmacological profiling of disulfiram using human tumor cell lines and human tumor cells from patients
  • 2007
  • Ingår i: Biochemical Pharmacology. - 0006-2952. ; 73:1, s. 25-33
  • Tidskriftsartikel (refereegranskat)abstract
    • The thiocarbamate drug disulfiram has been used for decades in the treatment of alcohol abuse. Disulfiram induces apoptosis in a number of tumor cell lines and was recently by us proposed to act as a 26S proteasome inhibitor. In this work we characterized disulfiram in vitro with regard to tumor-type specificity, possible mechanisms of action and drug resistance and cell death in human tumor cell lines and in 78 samples of tumor cells from patients using the fluorometric microculture cytotoxicity assay and the automated fluorescence-imaging microscope ArrayScan®. Disulfiram induced cytotoxicity in a biphasic pattern in both cell lines and patient tumor cells. Disulfiram induced apoptosis as measured by cell membrane permeability, nuclear fragmentation/condensation and caspase-3/7 activation using high content screening assays. For many of the cell lines tested disulfiram was active in sub-micromolar concentrations. When comparing the log IC50 patterns with other cytotoxic agents, disulfiram showed low correlation (R < 0.5) with all drugs except lactacystin (R = 0.69), a known proteasome inhibitor, indicating that the two substances may share mechanistic pathways. Disulfiram was more active in hematological than in solid tumor samples, but substantial activity was observed in carcinomas of the ovary and the breast and in non-small cell lung cancer. Disulfiram also displayed higher cytotoxic effect in cells from chronic lymphocytic leukemia than in normal lymphocytes (p < 0.05), which may indicate some tumor selectivity. These results together with large clinical experience and relatively mild side effects encourage clinical studies of disulfiram as an anti-cancer agent.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-9 av 9
 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy