Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

eIF4G1, a critical component of the eIF4F complex, is required for cap-dependent mRNA translation, a process necessary for tumor growth and survival. However, the role of eIF4G1 has not been evaluated in Prostate Cancer (PCa). We observed an increased eIF4G1 protein levels in PCa tissues as compared to normal tissues. Analysis of the TCGA data revealed that eIF4G1 gene expression positively correlated with higher tumor grade and stage. Furthermore, eIF4G1 was over-expressed and or amplified, in 16% patients with metastatic PCa (SU2C/PCF Dream Team dataset) and in 59% of castration-resistant prostate cancer (CRPC) patients (Trento/Cornell/Broad dataset). We showed for the first time that eIF4G1 expression was increased in PCa and that increased eIF4G1 expression associated with tumor progression and metastasis. We also observed high protein levels of eIF4G1 in PCa cell lines and prostate tissues from the TRAMP model of PCa as compared to normal prostate cell line and prostate tissues from the wild type mice. Knockdown of eIF4G1 in PCa cells resulted in decreased Cyclin D1 and p-Rb protein level, cell cycle delay, reduced cell viability and proliferation, impaired clonogenic activity, reduced cell migration and decreased mRNA loading to polysomes. Treatment with eIF4G complex inhibitor also impaired prostasphere formation. eIF4G1 knockdown or treatment with eIF4G complex inhibitor sensitized CRPC cells to Enzalutamide and Bicalutamide. Our results showed that eIF4G1 plays an important role in PCa growth and therapeutic resistance. These data suggested that eIF4G1 functions as an oncoprotein and may serve as a novel target for intervention in PCa and CRPC.
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PMID:Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis. 2974 19

To date, how to select an appropriate strategy to treat advanced prostate cancer (PCa) patients with tumor progression after abiraterone acetate (AA) intervention is still confusing. Here, we conducted a case report and review of the literatures focused on this issue. A 63-year-old man presented initially with dysuria. Multiple pelvic bone metastases but no other lesions were detected. He was subsequently diagnosed with PCa after biopsies, the initial clinical staging was cT2cNxM1. This patient was treated with two periods of AA (first treatment: 16-month; secondary treatment: 19-month) combined with other therapeutic regimens [i.e., goserelin acetate, bicalutamide, docetaxel, and radical prostatectomy (RP), etc.], followed by a significant biochemical response during over 5 years of follow-up. In the present case report with 63 months of the treatment course, we found that patient with metastatic PCa who early received AA as the initial regimen could gain benefit from the retreatment of AA: minor progression and gain long-time survival. This "sandwich method" with AA administered initially, withdrawal, and sequentially following Bicalutamide, Docetaxel, RP, and retreatment of AA may prolong the response time of AA retreatment and delay the progression of metastatic PCa, which reminds clinicians should pay attention to this phenomenon and explore the underlying mechanisms.
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PMID:Treatment gains from the "sandwich method" of abiraterone acetate for men with metastatic prostate cancer: a case report and sharing of our experience. 3267 30