480 research outputs found
Identification of novel somatic fusions of ERG-VEGFA, TMPRSS2-ERG, and VEGFA-TMPRSS2 in prostate cancer treated with anlotinib and androgen deprivation therapy: A case report
The TMPRSS2-ERG fusion gene has frequently been found in prostate cancer and is associated with malignancy. Identifying novel fusions will help to stratify patients and establish patient-tailored therapies. A 78-year-old man presented to our hospital with severe symptoms of urinary urgency and frequency for 2 years, as well as severe bone pain for 1 year. He was diagnosed with metastatic prostate cancer with a Gleason score of 5 + 5. Three gene fusions, ERG_VEGFA, TMPRSS2_ERG, and VEGFA_TMPRSS2, were identified in the patient\u27s prostate cancer tissue. Notably, administration of the tyrosine kinase inhibitor, anlotinib, in combination with a gonadotropin-releasing hormone agonist (GnRHa) and abiraterone, reduced the patient\u27s bone pain and also stabilized his prostate cancer for more than 2 years. This is the first report of somatic fusions among the VEGFA, ERG, and TMPRSS2 genes in cancer tissues from a patient with prostate cancer who responded well to antiangiogenic treatment combined with a GnRHa and abiraterone
Transduced PEP-1-Heme Oxygenase-1 Fusion Protein Attenuates Lung Injury in Septic Shock Rats
Oxidative stress and inflammation have been identified to play a vital role in the pathogenesis of lung injury induced by septic shock. Heme oxygenase-1 (HO-1), an effective antioxidant and anti-inflammatory and antiapoptotic substance, has been used for the treatment of heart, lung, and liver diseases. Thus, we postulated that administration of exogenous HO-1 protein transduced by cell-penetrating peptide PEP-1 has a protective role against septic shock-induced lung injury. Septic shock produced by cecal ligation and puncture caused severe lung damage, manifested in the increase in the lung wet/dry ratio, oxidative stress, inflammation, and apoptosis. However, these changes were reversed by treatment with the PEP-1-HO-1 fusion protein, whereas lung injury in septic shock rats was alleviated. Furthermore, the septic shock upregulated the expression of Toll-like receptor 4 (TLR4) and transcription factor NF-κB, accompanied by the increase of lung injury. Administration of PEP-1-HO-1 fusion protein reversed septic shock-induced lung injury by downregulating the expression of TLR4 and NF-κB. Our study indicates that treatment with HO-1 protein transduced by PEP-1 confers protection against septic shock-induced lung injury by its antioxidant, anti-inflammatory, and antiapoptotic effects
Germline Mutations in Patients With Early-Onset Prostate Cancer.
Objective: To investigate the inherited mutations and their association with clinical features and treatment response in young-onset prostate cancer patients.
Method: Targeted gene sequencing on 139 tumor susceptibility genes was conducted with a total of 24 patients diagnosed with PCa under the age of 63 years old. Meanwhile, the related clinical information of those patients is collected and analyzed.
Results: Sixty-two germline mutations in 45 genes were verified in 22 patients.
Conclusion: Mutations in DRGs are more prevalent in early-onset PCa with advanced clinical stages, and these patients had shorter progression-free survival. ADT Combined with either radiotherapy or chemotherapy may be effective in treating PCa caused by HRR-related gene mutations
Statistical Origin of Constituent-Quark Scaling in the QGP hadronization
Nonextensive statistics in a Blast-Wave model (TBW) is implemented to
describe the identified hadron production in relativistic p+p and
nucleus-nucleus collisions. Incorporating the core and corona components within
the TBW formalism allows us to describe simultaneously some of the major
observations in hadronic observables at the Relativistic Heavy-Ion Collider
(RHIC): the Number of Constituent Quark Scaling (NCQ), the large radial and
elliptic flow, the effect of gluon saturation and the suppression of hadron
production at high transverse momentum (pT) due to jet quenching. In this
formalism, the NCQ scaling at RHIC appears as a consequence of non-equilibrium
process. Our study also provides concise reference distributions with a least
chi2 fit of the available experimental data for future experiments and models.Comment: 4 pages, 3 figures; added two tables, explained a little bit more on
TBW_p
Genotype-phenotype correlation in patients with 21-hydroxylase deficiency.
INTRODUCTION: 21-hydroxylase deficiency (21OHD) is the most common cause of congenital adrenal hyperplasia (CAH). However, patients with 21OHD manifest various phenotypes due to a wide-spectrum residual enzyme activity of different CYP21A2 mutations.
METHODS: A total of 15 individuals from three unrelated families were included in this study. Target Capture-Based Deep Sequencing and Restriction Fragment Length Polymorphism was conducted on peripheral blood DNA of the three probands to identify potential mutations/deletions in CYP21A2; Sanger sequencing was conducted with the DNA from the family members of the probands.
RESULTS: Dramatically different phenotypes were seen in the three probands of CAH with different compound heterozygous mutations in CYP21A2. Proband 1 manifested simple virilizing with mutations of 30-kb deletion/c.[188A\u3eT;518T\u3eA], the latter is a novel double mutants classified as SV associated mutation. Although both probands carry the same compound mutations [293-13C\u3eG]:[518T\u3eA], gonadal dysfunction and giant bilateral adrenal myelolipoma were diagnosed for proband 2 and proband 3, respectively.
CONCLUSION: Both gender and mutations contribute to the phenotypes, and patients with the same compound mutations and gender could present with different phenotypes. Genetic analysis could help the etiologic diagnosis, especially for atypical 21OHD patients
PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma.
For clear cell renal cell carcinoma (ccRCC), lipid deposition plays important roles in the development, metastasis, and drug resistance. However, the molecular mechanisms underlying lipid deposition in ccRCC remain largely unknown. By conducting an unbiased CRISPR-Cas9 screening, we identified the epigenetic regulator plant homeodomain finger protein 8 (PHF8) as an important regulator in ccRCC lipid deposition. Moreover, PHF8 is regulated by von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF) axis and essential for VHL deficiency-induced lipid deposition. PHF8 transcriptionally up-regulates glutamate-ammonia ligase (GLUL), which promotes the lipid deposition and ccRCC progression. Mechanistically, by forming a complex with c-MYC, PHF8 up-regulates TEA domain transcription factor 1 (TEAD1) in a histone demethylation-dependent manner. Subsequently, TEAD1 up-regulates GLUL transcriptionally. Pharmacological inhibition of GLUL by l-methionine sulfoximine not only repressed ccRCC lipid deposition and tumor growth but also enhanced the anticancer effects of everolimus. Thus, the PHF8-GLUL axis represents a potential therapeutic target for ccRCC treatment
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