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DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.
Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate.
Mitf regulation of Dia1 controls melanoma proliferation and invasiveness.
In melanomas invasiveness can be regulated epigenetically by the microphthalmia-associated transcription factor, Mitf, via regulation of the DIAPH1 gene encoding the diaphanous-related formin Dia1 that promotes actin polymerization and coordinates the actin cytoskeleton and microtubule networks at the cell periphery.
Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis.
The frequencies of IL-17-positive and IL-22-positive CD4+ T cells were increased in PBMCs from patients with ankylosing spondylitis and patients with RA, resulting in secretion of higher quantities ofIL-17 by PB MCs following stimulation, and data support the hypothesis that Th17 cells, particularly when present in excess of Il-10-producing cells, are involved in the pathogenesis of inflammatory arthritis.
Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression
It is shown that Mitf can act as a novel anti-proliferative transcription factor able to induce a G1 cell-cycle arrest that is dependent on Mitf-mediated activation of the p21Cip1 (CDKN1A) cyclin-dependent kinase inhibitor gene.
Plasma AR and abiraterone-resistant prostate cancer
- A. Romanel, Delila Gasi Tandefelt, G. Attard
- Biology, MedicineScience Translational Medicine
- 4 November 2015
Tumor DNA samples from the blood of 97 patients with castration-resistant prostate cancer were analyzed and found that androgen receptor amplifications were present from the beginning and correlated with abiraterone resistance, suggesting that detection of these amplifications should be useful for identifying abiraton-resistant cancers before starting treatment.
Endoplasmic reticulum stress-induced transcription factor, CHOP, is crucial for dendritic cell IL-23 expression
- J. Goodall, Changxing Wu, J. Gaston
- BiologyProceedings of the National Academy of Sciences
- 27 September 2010
Investigation of proinflammatory cytokine expression by monocyte-derived dendritic cells is affected by the induction of ER stress found the IL-23 gene was found to be a target of the ER stress-induced transcription factor C/EBP homologous protein (CHOP), which exhibited enhanced binding in the context of both ER stress and TLR stimulation.
Beta-catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development.
Stabilized beta-catenin reduces the number of melanoblasts in vivo and immortalizes primary skin melanocytes by silencing the p16(Ink4a) promoter, revealing that synergy between the Wnt and mitogen-activated protein (MAP) kinase pathways may represent an important mechanism underpinning the genesis of melanoma.
Tumor clone dynamics in lethal prostate cancer
A management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers is introduced.
Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells.
It is shown that Brn-2 also regulates invasiveness and directly represses Mitf expression, providing a striking illustration of melanoma tumor heterogeneity with implications for melanoma therapy.
The Brn-2 Transcription Factor Links Activated BRAF to Melanoma Proliferation
- J. Goodall, C. Wellbrock, T. Dexter, K. Roberts, R. Marais, C. Goding
- BiologyMolecular and Cellular Biology
- 1 April 2004
The results suggest that the high levels of Brn-2 expression observed in melanomas link BRAF signaling to increased proliferation.