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Acquired drug resistance is the major reason why patients fail to respond to cancer therapies. It is a challenging task to determine the tipping point of endocrine resistance and detect the associated molecules. Derived from new systems biology theory, the dynamic network biomarker (DNB) method is designed to quantitatively identify the tipping point of a drastic system transition and can theoretically identify DNB genes that play key roles in acquiring drug resistance. We analyzed time-course mRNA sequence data generated from the tamoxifen-treated estrogen receptor (ER)-positive MCF-7 cell line, and identified the tipping point of endocrine resistance with its leading molecules. The results show that there is interplay between gene mutations and DNB genes, in which the accumulated mutations eventually affect the DNB genes that subsequently cause the change of transcriptional landscape, enabling full-blown drug resistance. Survival analyses based on clinical datasets validated that the DNB genes were associated with the poor survival of breast cancer patients. The results provided the detection for the pre-resistance state or early signs of endocrine resistance. Our predictive method may greatly benefit the scheduling of treatments for complex diseases in which patients are exposed to considerably different drugs and may become drug resistant. [ABSTRACT FROM AUTHOR]

We developed a computational method to infer the complementarity determining region 3 (CDR3) sequences of tumor infiltrating T-cells in 9,142 RNA-seq samples across 29 cancer types. We identified over 600 thousand CDR3 sequences, including 15% with full-length. CDR3 sequence length distribution and amino acid conservation, as well as variable gene usage of infiltrating T-cells in many tumors, except brain and kidney cancers, resembled those in the peripheral blood of healthy donors. We observed a strong association between T-cell diversity and tumor mutation load, and predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multiple cancers. Finally, we identified 3 potential immunogenic somatic mutations based on their co-occurrence with CDR3 sequences. One of them, PRAMEF4 F300V, was predicted to bind strongly to both MHC-I and MHC-II, with matched HLA types in its carriers. Our analyses have the potential to simultaneously identify immunogenic neoantigens and the tumor-reactive T-cell clonotypes.

In this paper, Mn 2+ /Ln 3+ -doped hexagonal phase (β-) NaGdF 4 :Ce (Ln = Tb, Dy, Eu) nanomaterials with subtly tuned multicolor output have been successfully synthesized by a typical simple hydrothermal method using polyethylene glycol (PEG) as a surface modifying agent. The crystal structures, morphology, luminescence performance, and energy transfer (ET) mechanism of the synthesized NaGdF 4 nanoparticles (NPs) were investigated in detail. It is found that due to the effective ET between Ce 3+ and Mn 2+ /Ln 3+ , the multicolor down-conversion (DC) emission phosphors can yield three major emission bands in the visible region including blue, green and red. Moreover, the white emission could be realized through manipulating the doping ratio of Ce 3+ , Dy 3+ and Eu 3+ with suitable concentration in β-NaGdF 4 NPs through effective resonance-type ET under the irradiation of 273 nm. And the corresponding CIE1931 coordinates were calculated to be (0.31, 0.32), which is near the normative white emission (0.33, 0.33). All the multicolor tuning and white emission results evidently suggest that the present Ce 3+ and Mn 2+ /Ln 3+ -doped β-NaGdF 4 NPs are feasible phosphors for potential applications in white-light emitters, full-color displays and photonic devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)