Oncotarget
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The PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking. ⋯ In spite of improved treatment options and increasing knowledge of molecular alterations in HNSCC, the survival rate has not been dramatically changed in the past decades. Pies are missing in HNSCC. One promising candidate in cancer immune therapy is PD-L1. Drugs targeting PD-L1 or its receptor PD-1 are subject of several clinical studies in different cancer entities. However, comprehensive data about PD-L1 expression in HNSCC and therefore a rational basis for anti PD-L1/PD-1 therapy in HNSCC is lacking. Here, we provide wide-ranging data about PD-L1 expression in HNSCC of all major localizations. We observed a strong correlation between expression of PD-L1 and reduced overall survival time. Furthermore, high PD-L1 expression was identified as a strong prognostic factor of patient's outcome when verified together with recognized prognostic factors.
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Dipeptidyl peptidase 4 inhibitor (DPP4i) use potentially slows the progression of diabetic kidney disease, but its effects on the risk of acute kidney injury (AKI) are unclear. We aimed to assess the association between DPP4i use and incident AKI episodes from a nationally representative cohort in Taiwan. ⋯ DPP4i use is associated with reduced risk of mild and severe forms of AKI among patients with incident DM. DPP4i may be an important class of anti-glycaemic agent with reno-protective effects.
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Immune checkpoint inhibitors (ICIs) have been approved for patients with advanced non-small-cell lung cancer (NSCLC), regardless of histology. However, histologic subtypes of NSCLC may influence treatment outcomes of ICIs. We conducted this meta-analysis to investigate if there is difference in survival benefits of ICIs between squamous (SQ) and non-squamous (non-SQ) NSCLC. ⋯ For patients with non-SQ NSCLC, however, ICIs were not associated with significant improvement of PFS (HR = 0.88 [95% CI, 0.67-1.16], P = 0.37). In terms of overall survival (OS), ICIs prolonged OS significantly in both SQ (HR = 0.71 [95% CI, 0.60-0.83], P < 0.0001) and non-SQ NSCLC (HR = 0.77 [95% CI, 0.63-0.94], P = 0.01). In conclusion, this meta-analysis indicates that ICIs significantly prolong OS in both SQ and non-SQ NSCLC.
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The implications of lncRNAs regarding fetal hemoglobin (HbF) induction in hemoglobin disorders remain poorly understood. In this study, microarray analysis was performed to profile lncRNAs, miRNAs and mRNAs in individuals with hereditary persistence of fetal hemoglobin (HPFH), β-thalassemia carriers with high HbF levels and healthy controls. The results show aberrant expression of 862 lncRNAs, 568 mRNAs and 63 miRNAs in the high-HbF group compared with the control group. ⋯ Based on the results, lncRNAs likely contribute to increased HbF levels by activating expression of HBE1 and hematopoietic cell lineage-inducible molecules and by inhibiting that of apoptosis-inducible molecules. Finally, through construction of a competing endogenous RNA network, we found that 6 lncRNAs could bind competitively with miR-486-3p, resulting in increased HbF levels. Taken together, our findings provide new insights into the mechanisms of HbF induction and potentially provide new targets for the treatment of β-thalassemia major.
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The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib. ⋯ PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.