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Interleukin-23 Promotes a Distinct CD4 T Cell Activation State Characterized by the Production of Interleukin-17*
TLDR
Evidence is presented that murine IL-23, which is produced by activated dendritic cells, acts on memory T cells, resulting in elevated IL-17 secretion, which suggests that during a secondary immune response, IL- 23 can promote an activation state with features distinct from the well characterized Th1 and Th2 profiles.
Inhibition of the hedgehog pathway in advanced basal-cell carcinoma.
TLDR
GDC-0449, an orally active small molecule that targets the hedgehog pathway, appears to have antitumor activity in locally advanced or metastatic basal-cell carcinoma.
Smoothened Mutation Confers Resistance to a Hedgehog Pathway Inhibitor in Medulloblastoma
TLDR
These findings show that acquired mutations in a serpentine receptor with features of a G protein–coupled receptor can serve as a mechanism of drug resistance in human cancer.
IL-27 regulates IL-12 responsiveness of naïve CD4+ T cells through Stat1-dependent and -independent mechanisms
TLDR
It is reported here that IL-27 stimulation in developing murine T helper cells potently induces the expression of the major TH1-specific transcription factor T-bet and its downstream target IL-12R β2, independently of IFNγ.
A comprehensive transcriptional portrait of human cancer cell lines
TLDR
RNA sequencing and single-nucleotide polymorphism array analysis of 675 human cancer cell lines is described and multiple genome and transcriptome features are combined in a pathway-based approach to enhance prediction of response to targeted therapeutics.
Zebrafish genetic map with 2000 microsatellite markers.
TLDR
The zebrafish is the first vertebrate organism used for large-scale genetic screens seeking genes critical to development, and the 2000 markers presented here, using microsatellite (CA) repeats, provides 1.2-cM average resolution, close enough to begin positional cloning by YAC walks.
Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma
TLDR
Functional analysis of the mutations in MYCN, PTPN14 and LATS1 suggested their potential relevance in BCC tumorigenesis, and the mutational profiles, N-Myc and Hippo-YAP pathway target genes were upregulated.
Small molecule inhibition of GDC-0449 refractory smoothened mutants and downstream mechanisms of drug resistance.
TLDR
This work screened a panel of chemically diverse HPIs and identified several antagonists with potent in vitro activity against these GDC-0449-resistant SMO mutants, and found that these HPI resistant MB allografts retained their sensitivity to PI3K inhibition, presenting additional opportunities for the treatment of such tumors.
Characterization of two patched receptors for the vertebrate hedgehog protein family.
TLDR
Biochemical analysis of PTCH and PTCH2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with SMO, and Chromosomal localization ofPTCH2 places it on chromosome 1p33-34, a region deleted in some germ cell tumors, raising the possibility that PTCH 2 may be a tumor suppressor in Dhh target cells.
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