It has been reported that asprosin is a novel adipokine which is augmented in mice and humans with type 2 diabetes (T2DM). Asprosin stimulates hepatic gluconeogenesis under fasting conditions. However, the roles of asprosin in inflammation, endoplasmic reticulum (ER) stress, and insulin resistance in skeletal muscle has not been studied. In the currents study, elevated levels of asprosin expression were observed in adipocytes under hyperlipidemic conditions. Treatment of C2C12 myocytes with asprosin-induced ER stress markers (phosphorylated inositol-requiring enzyme 1 and eukaryotic initiation factor 2, and CHOP expression) as well as inflammation markers (interleukin-6 expression, phosphorylated IκB, and nuclear translocated nuclear factor-κβ). Finally, asprosin treatment promoted exacerbation of insulin sensitivity as determined by levels of insulin receptor substrate 1 and Akt phosphorylation as well as glucose uptake. Moreover, treatment of asprosin augmented protein kinase C-δ (PKCδ) phosphorylation and nuclear translocation, but suppressed messenger RNA expression of sarcoplasmic reticulum Ca 2+ ATPase 2b in both C2C12 myocytes and in mouse soleus skeletal muscle. These asprosininduced effects were markedly decreased in small interfering (si) RNA-mediated PKCδ-knockdown in C2C12 myocytes. These results suggest that asprosin results in impairment of insulin sensitivity in skeletal muscle through PKCδ-associated ER stress/inflammation pathways and may be a valuable strategy for management of insulin resistance and T2DM.

Purpose: Although fusion genes serve as an effective target in hematologic malignancies, recurrent gene fusion events are relatively rare in solid tumors. To detect recurrent novel fusion transcripts we performed whole transcriptome sequencing primary breast cancer samples.Experimental Design: Whole-transcriptome sequencing of 120 fresh-frozen primary breast cancer samples and five adjacent normal breast tissues using the Illumina HiSeq2000 platform was performed. Three different fusion-detecting tools (deFuse, Chimerascan, and TopHat) were used, and the results were compared.Results: These tools detected 3831, 6630 and 516 fusion transcripts (FTs) overall.We primarily focused on the results obtained using the deFuse software. More FTs were identified from HER2 subtype breast cancer samples than from the luminal or triple-negative subtypes (p < 0.05). Seventy fusion candidates were selected for validation, and 32 (45.7%) were confirmed by RT-PCR and Sanger sequencing. Of the validated fusions, six were recurrent (found in 2 or more samples), three were in-frame (PRDX1-AKR1A1, TACSTD2-OMA1 and C2CD2-TFF1) and three were off-frame (CEACAM7-CEACAM6, CYP4X1-CYP4Z2P, and EEF1DP3-FRY).Notably, the novel read-through fusion, EEF1DP3-FRY, was identified and validated in 6.7% (8/120) of the breast cancer samples. This off-frame fusion results in early truncation of the FRY gene, which plays a key role in the structural integrity ii during mitosis. Three previously reported fusions, PPP1R1B-STARD3, MFGE8-HAPL, and ETV6-NTRK3, were detected in 8.3%, 3.3% and 0.8% of the 120 samples, respectively, by both deFuse and Chimerascan. The recently reported MAGI3-AKT3 fusion was not detected in our analysis. Conclusion

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PurposePrevious studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment.Materials and MethodsThis study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups.ResultsA total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS.ConclusionOur results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

PurposeThe American College of Surgeons Oncology Group Z0011 trial reported that complete dissection of axillary lymph nodes (ALNs) may not be warranted in women with clinical T1-T2 tumors and one or two involved ALNs who were undergoing lumpectomy plus radiation followed by systemic therapy. The present study was conducted to identify preoperative imaging predictors of ≥ 3 ALNs.Materials and MethodsThe training set consisted of 1,917 patients with clinical T1-T2 and node negative invasive breast cancer. Factors associated with ≥ 3 involved ALNs were evaluated by logistic regression analysis. The validation set consisted of 378 independent patients. The nomogram was applied prospectively to 512 patients who met the Z0011 criteria.ResultsOf the 1,917 patients, 204 (10.6%) had ≥ 3 positive nodes. Multivariate analysis showed that involvement of ≥ 3 nodes was significantly associated with ultrasonographic and chest computed tomography findings of suspicious ALNs (p < 0.001 each). These two imaging criteria, plus patient age, were used to develop a nomogram calculating the probability of involvement of ≥ 3 ALNs. The areas under the receiver operating characteristic curve of the nomogram were 0.852 (95% confidence interval [CI], 0.820 to 0.883) for the training set and 0.896 (95% CI, 0.836 to 0.957) for the validation set. Prospective application of the nomogram showed that 60 of 512 patients (11.7%) had scores above the cut-off. Application of the nomogram reduced operation time and cost, with a very low re-operation rate (1.6%).ConclusionPatients likely to have ≥ 3 positive ALNs could be identified by preoperative imaging. The nomogram was helpful in selective intraoperative examination of sentinel lymph nodes.