GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines.

BACKGROUND: Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26. However, the positive regulators of ANKRD26 are still unknown. AIM: To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription. METHODS: Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26. Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26. Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients. RESULTS: In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26. Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26. Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26. In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients. CONCLUSION: We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.

Breast-conserving surgery is an appropriate procedure for centrally located breast cancer: a population-based retrospective cohort study.

BACKGROUND: The evidence of breast-conserving therapy (BCT) applied in centrally located breast cancer (CLBC) is absent. This study aims to investigate the long-term survival of breast-conserving therapy (BCT) in centrally located breast cancer (CLBC) compared with mastectomy in CLBC and BCT in non-CLBC. METHODS: Two hundred ten thousand four hundred nine women with unilateral T1-2 breast cancer undergoing BCT or mastectomy were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier survival curves were assessed via log-rank test. Propensity score matching (PSM) was used to balance baseline features, and the multivariable Cox model was used to estimate the adjusted hazard ratio [HR] and its 95% confidence interval [CI] for breast cancer-specific survival (BCSS) and overall survival (OS). RESULTS: With a median follow-up of 91 months, the BCSS and OS rates in patients who received BCT were greater than those patients treated with mastectomy in the entire CLBC set. Multivariable Cox analyses showed that CLBC patients who received BCT had better BCSS (HR = 0.67, 95%CI: 0.55-0.80, p < 0.001) and OS (HR = 0.78, 95%CI: 0.68-0.90, p = 0.001) than patients who received a mastectomy, but there were no significant differences of BCSS (HR = 0.65, 95%CI: 0.47-0.90, p = 0.009) and OS (HR = 0.82, 95%CI: 0.65-1.04, p = 0.110) after PSM. In patients treated with BCT, CLBC patients had a similar BCSS (HR = 0.99, 95%CI: 0.87-1.12, p = 0.850) but a worse OS (HR = 1.09, 95%CI: 1.01-1.18, p = 0.040) compared to that of the non-CLBC patient, but there was no significant difference both BCSS (HR = 1.05, 95%CI: 0.88-1.24, p = 0.614) and OS (HR = 1.08, 95%CI: 0.97-1.20, p = 0.168) after PSM. CONCLUSION: Our findings revealed that BCT should be an acceptable and preferable alternative to mastectomy for well-selected patients with CLBC.

Development and validation of nomograms for predicting survival in patients with de novo metastatic triple-negative breast cancer.

Metastatic triple-negative breast cancer (mTNBC) is a heterogeneous disease with a poor prognosis. Individualized survival prediction tool is useful for this population. We constructed the predicted nomograms for breast cancer-specific survival (BCSS) and overall survival (OS) using the data identified from the Surveillance, Epidemiology, and End Results database. The Concordance index (C-index), the area under the time-dependent receiver operating characteristic curve (AUC) and the calibration curves were used for the discrimination and calibration of the nomograms in the training and validation cohorts, respectively. 1962 mTNBC patients with a median follow-up was 13 months (interquartile range, 6-22 months), 1639 (83.54%) cases died of any cause, and 1469 (74.87%) died of breast cancer. Nine and ten independent prognostic factors for BCSS and OS were identified and integrated to construct the nomograms, respectively. The C-indexes of the nomogram for BCSS and OS were 0.694 (95% CI 0.676-0.712) and 0.699 (95% CI 0.679-0.715) in the training cohort, and 0.699 (95% CI 0.686-0.712) and 0.697 (95% CI 0.679-0.715) in the validation cohort, respectively. The AUC values of the nomograms to predict 1-, 2-, and 3-year BCSS and OS indicated good specificity and sensitivity in internal and external validation. The calibration curves showed a favorable consistency between the actual and the predicted survival in the training and validation cohorts. These nomograms based on clinicopathological factors and treatment could reliably predict the survival of mTNBC patient. This may be a useful tool for individualized healthcare decision-making.

[Effects of pyrethroids on the activity of gamma-aminobutyric acid transferase in rat brain].

OBJECTIVE: To study the effects of pyrethroids on the activity of gamma-aminobutyric acid transferase (GABAT) in rat brain. METHOD: The coupled enzyme ultraviolet spectrophotography was applied to observe the effects of deltamethrin (DM) and permethrin (PM) on the activities of GABAT in rat cerebral cortex, hippocampus, corpus striatum and cerebellum in vitro and in vivo. RESULTS: In vitro, DM and PM had no significant effects on the activities of GABAT in rat cerebral cortex, hippocampus, corpus striatum and cerebellum at the final concentration of 10(-9) - 10(-4) mol/L. When 37.5 mg/kg DM and 600 mg/kg PM were orally administrated to the rats at one time, the activities of GABAT in rat cerebral cortex, hippocampus and cerebellum in the DM group [(2.96 +/- 0.43), (2.13 +/-0.44), (5.12 +/- 1.36) nmol x mg pro(-1) x min(-1), respectively] were lower than those in the control group [(3.43 +/- 0.41), (2.68 +/- 0.47), (6.74 +/- 1.64) nmol x mg pro(-1) x min(-1)] (P < 0.05), and the activities of GABAT in rat cerebral cortex and hippocampus in the PM group [(4.57 +/- 0.30), (4.18 +/- 0.63) nmol.mg pro(-1) x min(-1), respectively] were higher than those in the control group (P < 0.05). When 12.5 mg/kg DM and 200 mg/kg PM were orally administrated to the rats once a day for consecutive five days, the two pesticides had no significant effects on the activities of GABAT in rat cerebral cortex, hippocampus, corpus striatum and cerebellum (P > 0.05). CONCLUSIONS: In vitro, DM and PM had no significant effects on the activity of GABAT in rat brain; in vivo, DM and PM may have different effects on the activity of GABAT in rat brain, which deserve further study.