A novel RNA in situ hybridization assay for the long noncoding RNA SChLAP1 predicts poor clinical outcome after radical prostatectomy in clinically localized prostate cancer.

Long noncoding RNAs (lncRNAs) are an emerging class of oncogenic molecules implicated in a diverse range of human malignancies. We recently identified SChLAP1 as a novel lncRNA that demonstrates outlier expression in a subset of prostate cancers, promotes tumor cell invasion and metastasis, and associates with lethal disease. Based on these findings, we sought to develop an RNA in situ hybridization (ISH) assay for SChLAP1 to 1) investigate the spectrum of SChLAP1 expression from benign prostatic tissue to metastatic castration-resistant prostate cancer and 2) to determine whether SChLAP1 expression by ISH is associated with outcome after radical prostatectomy in patients with clinically localized disease. The results from our current study demonstrate that SChLAP1 expression increases with prostate cancer progression, and high SChLAP1 expression by ISH is associated with poor outcome after radical prostatectomy in patients with clinically localized prostate cancer by both univariate (hazard ratio = 2.343, P = .005) and multivariate (hazard ratio = 1.99, P = .032) Cox regression analyses. This study highlights a potential clinical utility for SChLAP1 ISH as a novel tissue-based biomarker assay for outcome prognostication after radical prostatectomy

Frequency tuning behaviour of terahertz quantum cascade lasers revealed by a laser beating scheme

In the terahertz frequency range, the commercialized spectrometers, such as the Fourier transform infrared and time domain spectroscopies, show spectral resolutions between a hundred megahertz and a few gigahertz. Therefore, the high precision frequency tuning ability of terahertz lasers cannot be revealed by these traditional spectroscopic techniques. In this work, we demonstrate a laser beating experiment to investigate the frequency tuning characteristics of terahertz quantum cascade lasers (QCLs) induced by temperature or drive current. Two terahertz QCLs emitting around 4.2 THz with identical active regions and laser dimensions (150 μm wide and 6 mm long) are employed in the beating experiment. One laser is operated as a frequency comb and the other one is driven at a lower current to emit a single frequency. To measure the beating signal, the single mode laser is used as a fast detector (laser self-detection). The laser beating scheme allows the high precision measurement of the frequency tuning of the single mode terahertz QCL. The experimental results show that in the investigated temperature and current ranges, the frequency tuning coefficients of the terahertz QCL are 6.1 MHz/0.1 K (temperature tuning) and 2.7 MHz/mA (current tuning) that cannot be revealed by a traditional terahertz spectrometer. The laser beating technique shows potential abilities in high precision linewidth measurements of narrow absorption lines and multi-channel terahertz communications

The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression.

Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM-AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer

Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression

Multiple, complex molecular events characterize cancer development and progression(1,2). Deciphering the molecular networks that distinguish organ- confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high- throughput liquid- and- gas- chromatography- based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer ( 42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N- methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non- invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine- N- methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.Early Detection Research Network ; National Institutes of Health ; MTTC ; Clinical Translational Science Award ; Fund for Discovery of the University of Michigan Comprehensive Cancer Center ; University of Michigan Cancer Biostatistics Training Grant ; Doris Duke Charitable FoundationWe thank J. Granger for help in manuscript preparation, J. Siddiqui and R. Varambally for help with the clinical database, and A. Vellaichamy and S. Pullela for technical assistance. We thank K. Pienta for access to metastatic prostate cancer samples from the University of Michigan Prostate SPORE rapid autopsy programme. This work is supported in part by the Early Detection Research Network (A.M.C., J.T.W.), National Institutes of Health (A.S., S.P., J.B., T.M.R., D.G., G.S.O. and A.M.C.) and an MTTC grant (G.S.O. and A.S.). A.M.C. is supported by a Clinical Translational Science Award from the Burroughs Welcome Foundation. A. S. is supported by a grant from the Fund for Discovery of the University of Michigan Comprehensive Cancer Center. L. M. P. is supported by the University of Michigan Cancer Biostatistics Training Grant. A. M. C and S. P. are supported by the Doris Duke Charitable Foundation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62661/1/nature07762.pd

Inflammation-Induced Oxidative Stress Mediates Gene Fusion Formation in Prostate Cancer.

Approximately 50% of prostate cancers are associated with gene fusions of the androgen-regulated gene TMPRSS2 to the oncogenic erythroblast transformation-specific (ETS) transcription factor ERG. The three-dimensional proximity of TMPRSS2 and ERG genes, in combination with DNA breaks, facilitates the formation of TMPRSS2-ERG gene fusions. However, the origins of DNA breaks that underlie gene fusion formation in prostate cancers are far from clear. We demonstrate a role for inflammation-induced oxidative stress in the formation of DNA breaks leading to recurrent TMPRSS2-ERG gene fusions. The transcriptional status and epigenetic features of the target genes influence this effect. Importantly, inflammation-induced de novo genomic rearrangements are blocked by homologous recombination (HR) and promoted by non-homologous end-joining (NHEJ) pathways. In conjunction with the association of proliferative inflammatory atrophy (PIA) with human prostate cancer, our results support a working model in which recurrent genomic rearrangements induced by inflammatory stimuli lead to the development of prostate cancer

Plasmacytoid urothelial carcinoma: a rapid autopsy case report with unique clinicopathologic and genomic profile

Abstract Background Rapid (“warm”) autopsies of patients with advanced metastatic cancer provide important insight into the natural history, pathobiology and histomorphology of disease in treatment-resistant tumors. Plasmacytoid urothelial carcinoma (PUC) is a rare variant of urothelial carcinoma characterized by neoplastic cells morphologically resembling plasma cells. PUC is typically aggressive, high-stage at presentation, and associated with poor outcomes. Recurrence is common in PUC, with the majority of recurrences occurring in the peritoneum. Case presentation Here, we report rapid autopsy findings from a patient with recurrent PUC. The patient had persistent pain after cystoprostatectomy, although initial post-operative imaging showed no evidence of disease. Imaging obtained shortly before his death showed only subtle growth along vascular tissue planes; however, extensive disease was seen on autopsy. Plasmacytoid tumor cells formed sheets involving many serosal surfaces. Molecular interrogation confirmed a mutation in CDH1 exon 12 leading to early truncation of the CDH1 protein in the tumor cells. Conclusions The sheet-like growth pattern of PUC makes early phases of disease spread much more difficult to capture on cross-sectional imaging. Alternative forms of surveillance may be required for detection of recurrent PUC, and providers may need to treat based on symptoms and clinical suspicion.https://deepblue.lib.umich.edu/bitstream/2027.42/152229/1/13000_2019_Article_896.pd

Collaboration and Evolution of E-Commerce and Express Delivery Industry Supply Chain

Considering the contradictions between the electronic commerce (e-commerce) and its matching express delivery service, this paper investigates a supply chain regarding e-commerce and express delivery industry, in which collaborative operations of enterprises are discussed. The profitability and collaboration capability acting as order parameters and the rest of the influential resources including logistics, fund, information, and commodity are selected with their interrelations being examined based on servo theory of synergetics. Besides, evolutionary model of the e-commerce and express delivery industry is established and analyzed according to self-organization method of system dynamic theory to illustrate order parameters’ role in system evolution, and numerical analyses emerged to intuitively demonstrate the solutions. We conclude the work along with its results of significant references for investigating resource integrations by combining the two closely related businesses in an entire cooperative supply chain and providing guidelines for e-commerce and express delivery enterprises and industries in effective collaboration and system evolution

Collaboration and Evolution of E-Commerce and Express Delivery Industry Supply Chain

Considering the contradictions between the electronic commerce (e-commerce) and its matching express delivery service, this paper investigates a supply chain regarding e-commerce and express delivery industry, in which collaborative operations of enterprises are discussed. The profitability and collaboration capability acting as order parameters and the rest of the influential resources including logistics, fund, information, and commodity are selected with their interrelations being examined based on servo theory of synergetics. Besides, evolutionary model of the e-commerce and express delivery industry is established and analyzed according to self-organization method of system dynamic theory to illustrate order parameters’ role in system evolution, and numerical analyses emerged to intuitively demonstrate the solutions. We conclude the work along with its results of significant references for investigating resource integrations by combining the two closely related businesses in an entire cooperative supply chain and providing guidelines for e-commerce and express delivery enterprises and industries in effective collaboration and system evolution