Highlights d SAFB maintains higher-order organization of pericentromeric heterochromatin d SAFB interacts with repeat element RNAs such as MajSAT d SAFB drives phase separation that is promoted by MajSAT RNAs d Depletion of SAFB leads to a remodeling of 3D genome organization
Introduction: Surgery in SCLC is limited to very early stages, but several reports suggest a potential broader role. Little is known of the influence of microenvironment on the biology of SCLC.
Methods:We assessed the clinical prognostic factors in a large series of resected SCLC patients. The prognostic value of programmed cell death ligand 1 (PD-L1) expression in tumor cells and tumor infiltrating lymphocytes (TILs) and the percentage of CD3-, CD20-, CD45-and CD68-positive cells, were also investigated.Results: Two hundred five SCLC cases were resected between 2005 and 2015 and the median follow-up was 29 months (range: 2 to 135 months). Median survival of all patients was 69 months, and 5-year survival rates were 63.8%, 65.5%, 34.9%, and 0% for pathologic stages I, II, III, and IV, respectively. By multivariate analysis complete resection, cigarette index, lymph node metastatic rate, percentage of CD3-positive cells, PD-L1 expression in tumor cells, and TILs were independent prognostic factors. High PD-L1 expression was present in 3.2% and 33.5% of all tumor samples in tumor cells and TILs, respectively. High PD-L1 expression in tumor cells or TILs correlated with shorter survival, whereas high expression of CD3, CD20, and CD45 correlated with better survival.Conclusions: Resected stage II SCLC patients have similar survival as stage I, suggesting that surgery could be extended to patients with hilar lymph node involvement. Survival was better in tumors with a higher percentage of T cells and B cells, whereas PD-L1 expression in tumor cells and TILs correlated with worse survival, which suggests a potential role of immunotherapy in resected SCLC.
Because
of the lack of specific targets, the highly aggressive
triple negative breast cancer (TNBC) is unable to benefit from endocrine
therapy or conventional targeting therapy. Even worse, current diagnostic
and therapeutic approaches have limited value for TNBC. Therefore,
developing TNBC-specific theranostic probes for accurate diagnosis
and further selective therapy will build a powerful toolbox for TNBC
management. In this contribution, we developed a sequential strategy
to enhance the specificity of TNBC theranostics. In this theranostic
system, a versatile nanoprobe (Pep-SQ@USPIO) was integrated legitimately
for the fibronectin-targeting MR imaging and CTSB-activatable fluorescence
imaging, followed with enhanced photodynamic therapy (PDT) of TNBC.
First, the fibronectin overexpressed in the extracellular matrix (ECM)
of TNBC was used as a biomarker for targeting theranostics using the
Cys-Arg-Glu-Lys-Ala (CREKA) peptide. For another, the fluorescence
and PDT capacity of self-developed squaraine photosensitizer (SQ)
were prequenched by ultrasmall superparamagnetic iron oxide (USPIO),
an MR imaging contrast agent. Once the linker, Gly-Phe-Leu-Gly (GFLG)
peptide, was selectively cleaved by TNBC-derived CTSB, the liberated
SQ photosensitizer allowed light-up fluorescence imaging and enhanced
PDT of TNBC. Remarkably, this research demonstrates that tumor-ECM-targeting
and endogenous enzyme-activated nanoprobes open a new avenue for TNBC
theranostics.
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