Highlights d We build the genomic and transcriptomic landscape of 465 primary TNBCs d Chinese TNBC cases demonstrate more PIK3CA mutations and LAR subtype d Transcriptomic data classify TNBCs into four subtypes d Multi-omics profiling identifies potential targets within specific TNBC subtypes

A better understanding of the biological roles and the pathological consequences of thiol-dependent enzymes has emerged in recent years, and hence considerable progress has been made in identifying and delineating cysteine proteases that can be considered promising drug targets from those involved in housekeeping functions. Cysteine proteases have been implicated in a wide variety of disease processes ranging from cardiovascular, inflammatory, viral and immunological disorders to cancer. The first milestone in drug development of cysteine protease inhibitors has probably been reached, as IDN-6556 (a broad spectrum caspase inhibitor) has recently received Orphan Drug label by the U.S. Food and Drug Administration for use in the treatment of the patients undergoing liver transplantation and other solid organ transplantation. IDN-6556, which blocks apoptosis, is in Phase II human clinical trial in patients undergoing liver transplantation. In addition, more than ten cysteine protease inhibitors are presently at various phases of clinical development/trials for diverse diseases. This review emphasises on the new development from the literature reports since the year 2000 in the exploration of potential cysteine proteases as prospective drug targets, and the investigation of promising inhibitors that can potentially be developed for the treatment of human diseases. Transglutaminases, another class of thiol-dependent enzymes, are not discussed here.

A photoelectrochemical sensing strategy for highly sensitive detection of small molecules was developed based on the recognition interaction between aptamer and target molecule-ATP.

Background: Patients with early stage breast cancer with lymph nodes metastasis were proven to have more aggressive biologically phenotypes. This study aimed to build a nomogram to predict lymph node metastasis in patients with T1 breast cancer. Methods: We identified female patients with T1 breast cancer diagnosed between 2010 and 2014 in the Surveillance, Epidemiology and End Results database. The patients were randomized into training and validation sets. Univariate and multivariate logistic regressions were carried out to assess the relationships between lymph node metastasis and clinicopathological characteristics. A nomogram was developed and validated by a calibration curve and receptor operating characteristic curve analysis. Result: Age, race, tumour size, tumour primary site, pathological grade, oestrogen receptor (ER) status, progesterone receptor (PR) status and human epidermal growth factor receptor 2 (HER2) status were independent predictive factors of positive lymph node metastasis in T1 breast cancer. Increasing age, tumour size and pathological grade were positively correlated with the risk of lymph node metastasis. We developed a nomogram to predict lymph node metastasis and further validated it in a validation set, with areas under the receiver operating characteristic curves of 0.733 and 0.741 in the training and validation sets, respectively. Conclusions: A better understanding of the clinicopathological characteristics of T1 breast cancer patients might important for assessing their lymph node status. The nomogram developed here, if further validated in other large cohorts, might provide additional information regarding lymph node metastasis. Together with sentinel lymph node biopsy, this nomogram can help comprehensively predict lymph node metastasis.

Groucho (Gro)/Transducin-like enhancer of split (TLE) family proteins act as co-repressors of many transcription factors, and are involved in key signaling pathways. TLE1 negatively regulates inflammation and has potential roles in various diseases, including cancer. Previous studies suggest TLE1 could be used as a diagnostic marker and is a possible therapeutic target in various malignancies. It is therefore important to elucidate the mechanisms underlying TLE1 function during cancer initiation and metastasis. In this review, we highlight the functions of TLE1 in cancer and explore targeted approaches for cancer diagnosis and treatment. In particular, we discuss the TLE1 function in pancreatic cancer.

There were no statistically significantly differences in performance between the 2 types of FCs tested, and most participants would accept using either in the future.

Aim:The aim of this study is to explore the function of miR-20a in osteosarcoma. Materials & methods: miR-20a expression was measured by real-time PCR. miR-20a mimics, inhibitor and scramble siRNA were transfected into osteosarcoma cells to observe effects on colony formation and tumor growth. Moreover, relationships of miR-20a with TAK1 were investigated by western blot and luciferase activity. Results: We found that miR-20a was downregulated in osteosarcoma, and overexpression of miR-20a reduced colony formation and tumor growth. Furthermore, the data revealed that the function of miR-20a was probably exerted via targeting the TAK1 expression. Overexpression of miR-20a sensitizes the osteosarcoma cells to chemotherapeutic drugs. Conclusion: Our data identify the role of miR-20a in osteosarcoma growth, indicating its potential application in chemotherapy. Osteosarcoma is the most common primary malignant bone tumor with high morbidity in young adults and children, comprising 2.4% of all malignancies in pediatric patients and about 20% of all primary bone tumors [1]. It occurs mainly around regions with active bone growth and reparation. Osteosarcoma is highly aggressive and responded poorly to chemotherapy, and the 5-year survival rate for patients with metastatic osteosarcoma is only 14% [2]. Therefore, it is of extreme significance to elucidate novel molecular targets to develop alternative therapeutic target for this disease.miRNAs are a small family of noncoding RNAs that play important roles in the development of human diseases by negatively regulating gene expression at either post-transcriptional or translational levels [3,4]. Over the last decade, many miRNAs have been showed in regulating diverse biological events such as cell proliferation, differentiation and apoptotic processes [5][6][7], which are important in the development of cancer. Accumulated evidence indicated that aberrant expression of miRNAs associates with various types of cancer. These dysregulated miRNAs function as either oncogenes or tumor suppressors in carcinogenesis and progression of cancers [8,9]. Thus, to explore the aberrant miRNAs expression in osteosarcoma might lead to the discovery of novel miRNAs biomarkers.In this study, we found that miR-20a was downregulated in osteosarcoma samples and osteosarcoma cell lines, and the ectopic expression of miR-20a reduced cell colony formation in vitro and tumor growth in vivo. Furthermore, bioinformatic prediction and experimental validation revealed that the function of miR-20a was probably exerted via targeting the TAK1 expression. To translate these findings, overexpression of miR-20a sensitizes the osteosarcoma cells to chemotherapeutic drugs. Collectively, our data identify the key role of miR-20a in osteosarcoma growth, indicating its potential application in cancer chemotherapy.

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