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Score: 9.00 |
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| Title: Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity .
| | Author: Tsai J Lee JT Wang W Zhang J Cho H Mamo S Bremer R Gillette S Kong J Haass NK Sproesser K Li L Smalley KS Fong D Zhu YL Marimuthu A Nguyen H Lam B Liu J Cheung I Rice J Suzuki Y Luu C Settachatgul C Shellooe R Cantwell J Kim SH Schlessinger J Zhang KY West BL Powell B Habets G Zhang C Ibrahim PN Hirth P Artis DR Herlyn M Bollag G | | Journal: Proc Natl Acad Sci U S A Citation: V : 105 P : 3041-6 Year: 2008 Type: MEDLINE | | Literature: oryza Field: abstract Doc ID: pub18287029 Accession (PMID): 18287029 | | Abstract: BRAF ( V600E ) is the most frequent oncogenic protein kinase mutation known .
Furthermore , inhibitors targeting "active" protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer .
Therefore , we pursued the development of specific kinase inhibitors targeting B-Raf , and the V600E allele in particular .
By using a structure-guided discovery approach , a potent and selective inhibitor of active B-Raf has been discovered .
PLX4720 , a 7-azaindole derivative that inhibits B-Raf ( V600E ) with an IC ( 50 ) of 13 nM , defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays .
PLX4720 preferentially inhibits the active B-Raf ( V600E ) kinase compared with a broad spectrum of other kinases , and potent cytotoxic effects are also exclusive to cells bearing the V600E allele .
Consistent with the high degree of selectivity , ERK phosphorylation is potently inhibited by PLX4720 in B-Raf ( V600E ) -bearing tumor cell lines but not in cells lacking oncogenic B-Raf .
In melanoma models , PLX4720 induces cell cycle arrest and apoptosis exclusively in B-Raf ( V600E ) -positive cells .
In B-Raf ( V600E ) -dependent tumor xenograft models , orally dosed PLX4720 causes significant tumor growth delays , including tumor regressions , without evidence of toxicity .
The work described here represents the entire discovery process , from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-Raf ( V600E ) -driven tumors .
| | Supplemental links/files: reference in endnote online text related articles pubmed citation | |
Score: 2.00 |
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| Title: An endornavirus from a hypovirulent strain of the violet root rot fungus , Helicobasidium mompa .
| | Author: Osaki H Nakamura H Sasaki A Matsumoto N Yoshida K | | Journal: Virus Res .
Citation: V : 118 ( 1-2 ) P : 143-9 Year: 2006 Type: ARTICLE | | Literature: oryza Field: abstract Doc ID: pub16417937 Accession (PMID): 16417937 | | Abstract: We determined the complete nucleotide ( nt ) sequence ( 16 , 614 nt ) of a large double-stranded ( ds ) RNA ( referred to as L1 dsRNA ) , previously identified as the hypovirulence factor from strain V670 of the violet root rot fungus , Helicobasidium mompa .
The positive-strand of L1 dsRNA contained a long open reading frame ( ORF ) potentially encoding a protein of 5 , 373 amino acids ( molecular mass 603 , 080 Da ) with conserved motifs characteristic of RNA-dependent RNA polymerase ( RdRp ) and helicase .
The ORF is the longest so far reported in the fungal kingdom .
The putative RdRp and helicase were shown to be related to putative RdRps and helicases of members of the genus Endornavirus .
As is the case with endornaviruses , the coding ( sense ) strand of L1 dsRNA contained a discontinuity ( nick ) at nt position 2 , 552 .
A region between the RdRp and helicase domains of the polyprotein also had an amino acid sequence , resembling UDP glycosyltransferases ( UGTs ) in Oryza sativa endornavirus and Phytophthora endornavirus 1 .
Regions in the L1 dsRNA-encoded protein presumed to contain putative helicase , UGT and RdRp motifs were present at comparable positions to those in other endornaviruses .
L1 dsRNA of H mompa strain V670 was assigned to the genus Endornavirus , and here , we designate it as H mompa endornavirus 1-670 ( HmEV1-670 ) .
This represents the first report of a fungal endornavirus whose complete nucleotide sequence has been determined . | | Supplemental links/files: reference in endnote online text related articles pubmed citation | |
Score: 1.00 |
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| Title: Design of sphingomonad-detecting probes for a DNA array , and its application to investigate the behavior , distribution , and source of Rhizospherous sphingomonas and other sphingomonads inhabiting an acid sulfate soil paddock in Kalimantan , Indonesia .
| | Author: Hashidoko Y Kitagawa E Iwahashi H Purnomo E Hasegawa T Tahara S | | Journal: Biosci . Biotechnol . Biochem . Citation: V : 71 ( 2 ) P : 343-51 Year: 2007 Type: ARTICLE | | Literature: oryza Field: abstract Doc ID: pub17284854 Accession (PMID): 17284854 | | Abstract: Throughout Central and South Kalimantan , Indonesia , strongly acidic soil ( pH 2 . 1-3 . 7 ) is widely distributed , and the local acidic soil-tolerant plants , including local rice varieties , often possess sphingomonads in their rhizosphere and rhizoplane .
To investigate the behavior of sphingomonads inhabiting the rhizosphere of such acid-tolerant plants , we designed 13 different DNA array probes ( each of 72 mer ) specific to a group of sphingomonads , using a hypervariable V6 region of the 16S rRNA gene .
This DNA array system was used preliminarily for an analysis of microfloral dynamisms , particularly of sphingomonads , in acidic paddock ecosystems , and the results suggest that the acid-tolerant local rice shares rhizospherous sphingomonads with wild Juncus sp . , a predominant weed that thrives in acidic paddocks during the off-season for rice farming .
This tentative conclusion supports the bio-rationality of the traditional rice farming system with respect to functional rhizobacteria .
| | Supplemental links/files: reference in endnote online text related articles pubmed citation | |
Score: 1.00 |
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| Title: DGGE and 16S rDNA sequencing analysis of bacterial communities in colon content and feces of pigs fed whole crop rice .
| | Author: Wang HF Zhu WY Yao W Liu JX | | Journal: Anaerobe Citation: V : 13 P : 127-33 Year: 2007 Type: MEDLINE | | Literature: oryza Field: abstract Doc ID: pub17446093 Accession (PMID): 17446093 | | Abstract: The effect of feeding whole crop rice ( WCR ) to growing-finishing pigs at three levels 0 ( Control ) , 10% and 20% on bacterial communities in colon content and feces was analyzed using 16S rDNA-based techniques .
Amplicons of the V6-V8 variable regions of bacterial 16S rDNA were analyzed by denaturing gradient gel electrophoresis ( DGGE ) , cloning and sequencing .
The total number of DGGE bands and Shannon index of diversity for feces samples were higher in the pigs fed WCR-containing diets compared with the control , while a decrease trend was observed in these two parameters for colon content samples with the inclusion of WCR in the diets , although statistical differences were not significant .
In general , the intestinal bacterial communities were prone to form the cluster for pig fed the same diet .
Feeding of WCR induced the presence of special DGGE band with the sequence showing 99% similarity to that of Lactobacillus reuteri ( DSM 20016T ) .
The sequences of seven amplicons in total nine clones showed less than 97% similarity with those of previously identified or unidentified bacteria , suggesting that most bacteria in gastrointestinal tracts have not been cultured or identified .
The results suggest that the diet containing WCR did not affect the major groups of bacteria , but stimulated the growth of L reuteri-like species .
| | Supplemental links/files: reference in endnote online text related articles pubmed citation | |
