G-protein γ subunit GNG11 strongly regulates cellular senescence

Hossain, Mohammad Nazir; Sakemura, Risa; Fujii, Michihiko; Ayusawa, Dai

doi:10.1016/j.bbrc.2006.10.112

Cited by 53 publications

(46 citation statements)

References 30 publications

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“…Oxidative stress is thought to be a prominent risk factor for aging (Hossain et al, 2006) and can cause DNA double strand breaks to induce premature senescence (Chen et al, 2005). Here we found that the growth was retarded in the G1 phase of H 2 O 2 -induced premature senescence, which elicits the characteristics including morphology and proliferative capacity similar to those achieved during replicative senescence.…”

Section: Discussionmentioning

confidence: 74%

Comparison of global DNA methylation profiles in replicative versus premature senescence

Zhang

Yang

et al. 2008

Life Sciences

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Section: Discussionmentioning

confidence: 74%

Comparison of global DNA methylation profiles in replicative versus premature senescence

Zhang

Yang

et al. 2008

Life Sciences

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“…2A), and two other mutations involving PI3KCA F909 were reported by the Cosmic database (p.F909L and F909S). Furthermore, the presence of GNG11 amplification suggested activation of the Ras-Raf-MEK pathway in this tumor with wild-type RAS and RAF genes (14). To evaluate these therapeutic options, we treated the patient Avatar model.…”

Section: Resultsmentioning

confidence: 98%

Integrated Next-Generation Sequencing and Avatar Mouse Models for Personalized Cancer Treatment

Garralda

Paz

López-Casas

et al. 2014

Clinical Cancer Research

144

100

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Background Current technology permits an unbiased massive analysis of somatic genetic alterations from tumor DNA as well as the generation of individualized mouse xenografts (Avatar models). This work aimed to evaluate our experience integrating these two strategies to personalize the treatment of patients with cancer. Methods We performed whole-exome sequencing analysis of 25 patients with advanced solid tumors to identify putatively actionable tumor-specific genomic alterations. Avatar models were used as an in vivo platform to test proposed treatment strategies. Results Successful exome sequencing analyses have been obtained for 23 patients. Tumor-specific mutations and copy-number variations were identified. All samples profiled contained relevant genomic alterations. Tumor was implanted to create an Avatar model from 14 patients and 10 succeeded. Occasionally, actionable alterations such as mutations in NF1, PI3KA, and DDR2 failed to provide any benefit when a targeted drug was tested in the Avatar and, accordingly, treatment of the patients with these drugs was not effective. To date, 13 patients have received a personalized treatment and 6 achieved durable partial remissions. Prior testing of candidate treatments in Avatar models correlated with clinical response and helped to select empirical treatments in some patients with no actionable mutations. Conclusion The use of full genomic analysis for cancer care is encouraging but presents important challenges that will need to be solved for broad clinical application. Avatar models are a promising investigational platform for therapeutic decision making. While limitations still exist, this strategy should be further tested.

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“…Moreover there was a strong downregulation of the guanine nucleotide binding protein, gamma 11, GNG11 (FC -42.3), an inducer of cellular senescence in human cells [58]. Genes that control cell proliferation were also modulated in PsA biopsies even with very high fold change [59–66].…”

Section: Resultsmentioning

confidence: 99%

Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis

et al. 2015

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BackgroundPsoriatic arthritis (PsA) is an inflammatory arthritis whose pathogenesis is poorly understood; it is characterized by bone erosions and new bone formation. The diagnosis of PsA is mainly clinical and diagnostic biomarkers are not yet available. The aim of this work was to clarify some aspects of the disease pathogenesis and to identify specific gene signatures in paired peripheral blood cells (PBC) and synovial biopsies of patients with PsA. Moreover, we tried to identify biomarkers that can be used in clinical practice.MethodsPBC and synovial biopsies of 10 patients with PsA were used to study gene expression using Affymetrix arrays. The expression values were validated by Q-PCR, FACS analysis and by the detection of soluble mediators.ResultsSynovial biopsies of patients showed a modulation of approximately 200 genes when compared to the biopsies of healthy donors. Among the differentially expressed genes we observed the upregulation of Th17 related genes and of type I interferon (IFN) inducible genes. FACS analysis confirmed the Th17 polarization. Moreover, the synovial trascriptome shows gene clusters (bone remodeling, angiogenesis and inflammation) involved in the pathogenesis of PsA. Interestingly 90 genes are modulated in both compartments (PBC and synovium) suggesting that signature pathways in PBC mirror those of the inflamed synovium. Finally the osteoactivin gene was upregulared in both PBC and synovial biopsies and this finding was confirmed by the detection of high levels of osteoactivin in PsA sera but not in other inflammatory arthritides.ConclusionsWe describe the first analysis of the trancriptome in paired synovial tissue and PBC of patients with PsA. This study strengthens the hypothesis that PsA is of autoimmune origin since the coactivity of IFN and Th17 pathways is typical of autoimmunity. Finally these findings have allowed the identification of a possible disease biomarker, osteoactivin, easily detectable in PsA serum.

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G-protein γ subunit GNG11 strongly regulates cellular senescence

Cited by 53 publications

References 30 publications

Comparison of global DNA methylation profiles in replicative versus premature senescence

Comparison of global DNA methylation profiles in replicative versus premature senescence

Integrated Next-Generation Sequencing and Avatar Mouse Models for Personalized Cancer Treatment

Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis

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