bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract C14: Pim kinase inhibitors sensitize prostate cancer cells to apoptosis triggered by Bcl-2 family inhibitor ABT-737
Authors: Song Jin H. , Kraft Andrew S.
Published: May 2013

Pim serine/threonine kinases contribute to prostate tumorigenesis and therapeutic resistance, yet Pim kinase inhibitors appear to have only limited effects on prostate cancer cell survival. Since overexpression of Bcl-2 family members are implicated in chemotherapeutic resistance in prostate cancer, we investigated the cooperative effects of Pim kinase inhibition with ABT-737, a small molecule antagonist of Bcl-2 family members. Strikingly, the addition of ABT-737 to Pim inhibitors triggered a robust apoptosis of prostate cancer cells in vitro and in vivo. Pim inhibitors decreased levels of the Bcl-2 family member Mcl-1, both by blocking 5′- cap dependent translation and decreasing protein half life. Additionally, Pim inhibition transcriptionally increased levels of the BH3 protein Noxa by activating the unfolded protein response (UPR), lead to eIF-2α phosphorylation and increased expression of CHOP. Increased levels of Noxa also inactivated the remaining levels of Mcl-1 protein activity. Notably, these specific protein changes were essential to the apoptotic process because ABT-737 did not inhibit Mcl-1 protein activity and Mcl-1 overexpression blocked the apoptotic activity of ABT-737. Our results therefore suggest that this combination treatment could be developed as a potential therapy for human prostate cancer where overexpression of Pim kinases and antiapoptotic Bcl-2 family members drives tumor cell resistance to current anticancer therapies.

Citation Format: Jin H. Song, Andrew S. Kraft. Pim kinase inhibitors sensitize prostate cancer cells to apoptosis triggered by Bcl-2 family inhibitor ABT-737 [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C14.
Abstract C2: Nuclear factor I/C collaborates with androgen receptor in transcription regulation in prostate cancer
Authors: Yang Chong , Chng Kern Rei
Published: May 2013

Androgen receptor (AR) plays an important role in mediating the transcriptional regulatory network directing prostate cancer initiation, development and progression. In order to gain insights into the AR-dependent transcriptional regulatory network, we utilized Chromatin Immunoprecipitation-sequencing (ChIP-Seq) and generated genome-wide binding maps of AR in the LNCaP prostate cancer cell line. From our bioinformatic analyses of AR binding sites (ARBS), we found an enrichment of motifs belonging to the NFI family. We demonstrate that one member of the NFI family, NFIC, which has been shown to be over-expressed in clinical prostate tumors, overlaps with a large fraction of ARBS across the genome. Surprisingly, the recruitment of NFIC was independent of DHT treatment, indicating NFIC as a potential pioneer factor. Moreover, we showed NFIC was required for the global modulation of AR-dependent target genes including KLK2, KLK3, and TMPRSS2. Finally, we found that AR and NFIC co-associated genes are preferentially involved in cellular movement and apoptosis. Together, our results suggest NFIC is a novel collaborative factor in AR-mediated transcription.

Citation Format: Chong Yang, Kern Rei Chng. Nuclear factor I/C collaborates with androgen receptor in transcription regulation in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C2.
Abstract C21: LincRNA expression data analysis identifies prostate tumor subtypes with distinct biological processes
Authors: Mello-Grand Maurizia , Singh Vijay K. , Ghimenti Chiara , Scatolini Maria , Longoni Nicole , Curti Laura , Zitella Andrea , Gontero Paolo , Catapano Carlo V. , Carbone Giuseppina M. , Chiorino Giovanna
Published: May 2013

Prostate cancer (PCa) shows tremendous heterogeneity which makes it difficult to identify patients with an increased risk of disease recurrence. A better understanding of the biological mechanism of prostate cancer formation and progression is crucial for the discovery of new markers for this disease. In recent years it has become apparent that different non-coding RNAs are also implicated in prostate cancer. Several microRNAs are now associated with progression and classification of prostate cancer and other malignancies. The role played in progression and differentiation of distinct PCa subtypes by a recently discovered class of non-coding RNAs, called large intergenic non-coding RNAs (lincRNAs), has remained unexplored. LincRNAs are believed to have major consequences on gene expression patterns through epigenetic mechanisms. Thousands of lincRNAs have been identified in human tissues, but only few have been functionally characterized. To assess the role of lincRNAs in PCa, we analysed the expression pattern of nearly 28000 Entrez genes and 7500 unique lincRNAs in 56 primary PCas and 5 normal prostate tissues, using Agilent 8x60k arrays. Unsupervised clustering over 1610 lincRNAs, selected after filtering out non informative probes, classified 61 samples into 5 distinct classes. Anova analysis was done to identify genes specifically over or under expressed in each cluster and was followed by functional annotation analysis. Normal samples were separated into a cluster characterized by the down regulation of genes involved in chemotaxis and intracellular signaling cascade. The four tumor clusters showed up regulation of distinct biological processes, like cell cycle, chromatin organization and immune response, together with deregulation of MAP-kinase signaling through EGFR and members of the RAS family oncogene. These results show that sample classification based on lincRNA profiling is able to separate tumors into subgroups with distinct biological processes.

Citation Format: Maurizia Mello-Grand, Vijay K. Singh, Chiara Ghimenti, Maria Scatolini, Nicole Longoni, Laura Curti, Andrea Zitella, Paolo Gontero, Carlo V. Catapano, Giuseppina M. Carbone, Giovanna Chiorino. LincRNA expression data analysis identifies prostate tumor subtypes with distinct biological processes [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C21.
Abstract C25: The 16p13.3 genomic gain in prostate cancer: A role for PDK1 in disease progression
Authors: Choucair Khalil , Brimo Fadi , Cunha Isabela W , Aprikian Armen , Gleave Martin , Lapointe Jacques , Guérard Karl-Philippe , Ejdelman Joshua , Chevalier Simone , Yoshimoto Maisa , Scarlata Eleonora , Fazli Ladan , Sircar Kanishka , Squire Jeremy A.
Published: May 2013

Prostate cancer (PCa) is a leading cause of cancer death and distinguishing life threatening tumors from indolent ones is a major challenge. The identification and characterization of genomic alterations associated with advanced disease may lead to the development of new markers of progression and more efficient therapeutic approaches. Array-CGH data have shown that gain of chromosome 16p13.3 to be associated with lymph node (LN) metastases of PCa, but this region remained uncharacterized. Our goal was to establish the prognostic value of 16p13.3 gain, and identify the cancer relevant genes residing within this region. In this study, we performed Fluorescence In Situ Hybridization (FISH) to detect the copy number gain of chromosome 16p13.3 in 75 PCa samples including 10 lymph node (LN) metastases and their matched primary tumors, 9 transurethral resections of prostate (TURP) tissue samples of castration-resistant prostate cancer (CRPC), and 46 additional primary PCa specimens with clinicopathological parameters. We detected the gain in 5/10 LN metastases and 3/5 matched primary tumors, 3/9 CRPC samples, and 9/46 (20 %) primary tumors. In the latter set of samples, the 16p13.3 alteration was associated with high Gleason score (P=0.002) and elevated pre operative prostate specific antigen (PSA) levels (P=0.047). The levels of 16p13.3 gain were higher in LN metastasis and CRPC specimens compared to primary PCa (P>0.05). Chromosome mapping revealed a focal gain that spans PDPK1 encoding the 3-Phosphoinositide-dependent protein kinase-1 (PDK1). RNA interference-mediated knock down of PDK1 in three different PCa cell lines reduced cell motility without affecting growth and re-expressing PDK1 rescued motility (P>0.05). Our results support that the 16p13.3 gain is relevant to PCa progression and may represent an early marker of metastasis, since retrieved in primary PCa which is sampled by biopsies at time of diagnosis. PDK1 is implicated in PCa cell motility, a critical step for progression to metastasis. These findings provide further rationale for considering PDK1 as a target for cancer therapies and the development of new specific inhibitors of PDK1.

Citation Format: Khalil Choucair, Fadi Brimo, Isabela W Cunha, Armen Aprikian, Martin Gleave, Jacques Lapointe, Karl-Philippe Guérard, Joshua Ejdelman, Simone Chevalier, Maisa Yoshimoto, Eleonora Scarlata, Ladan Fazli, Kanishka Sircar, Jeremy A. Squire. The 16p13.3 genomic gain in prostate cancer: A role for PDK1 in disease progression [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C25.
Abstract C30: Use of targeted magnetic nanoparticles for imaging in prostate cancer
Authors: Russell Pamela J. , Soekmadji C , Thierry B , Cowin G , Strait-Gardner T , Verma N , Xiaochun Wang , Khatri A
Published: May 2013

Objective: Imaging techniques better than those conventionally used are needed to improve prostate cancer (PC) staging and read out of therapeutic effects in real time in treated patients. We aimed to perform preclinical evaluation of newly developed well-characterized, biocompatible, PC-targeted magnetic nanoparticles (MNPs) targeted to prostate cancer by conjugation with J591 (from N. Bander, Cornell, USA), an antibody which binds specifically to prostate specific membrane antigen (PSMA) which is expressed on the surface of ∼90% of PCs including castrate resistant prostate cancers; this binding results in internalization. The use of targeted MNPs should enhance the specificity and sensitivity of magnetic resonance imaging (MRI) to enable better staging of patients with PC and future targeted delivery of therapy.

Methods: MNPs were prepared, engineered to the appropriate size and conjugated with J591. There was no compromise in J591 cell binding or specificity for PSMA positive cells due to the conjugation, and Inductively Coupled Plasma Optical Emission Spectrometry and Prussian blue staining for iron indicated increased uptake of MNPs that were conjugated with the antibody. In vivo studies were performed in immunodepressed nude mice with subcutaneous LNCaP-LN3 (PSMA-positive) xenografts (post euthanasia using an 11.7T NMR system) or on live mice with orthotopic LNCaP xenografts, using a 16.4T MRI imaging system following intravenous injection of MNPs.

Results: Similar enhancement of MRI was obtained by NMR after injection of MNP or J591-MNP conjugates. Live imaging of mice given systemic J591-MNPs showed uptake into the prostate tumors.

Conclusions: The data indicate the promise of this technique in enabling imaging of small clusters of human prostate cancer cells. This should enable the effects of therapy to be determined by imaging in real time, improving patient management.

Citation Format: Pamela J. Russell, C Soekmadji, B Thierry, G Cowin, T Strait-Gardner, N Verma, Wang Xiaochun, A Khatri. Use of targeted magnetic nanoparticles for imaging in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C30.
Abstract C41: Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy.
Authors: Mirtti Tuomas , Leiby Benjamin E. , Stattin Pär , Bergh Anders , Nevalainen Marja T. , Abdulghani Junaid , Pavela Miia , Aaltonen Elina , Mamtani Anita , Alanen Kalle A. , Egevad Lars , Granfors Torvald , Josefsson Andreas
Published: May 2013

There is an urgent need for reliable markers to identify patients whose PCa is most likely to recur after initial therapy and progress to lethal disease. While Gleason score is considered the most accurate predictive marker for disease-specific mortality after primary treatment of localized prostate cancer (PCa), the majority of PCas cluster into intermediate group of Gleason scores 6 and 7 where there is considerable variation in treatment response, disease recurrence and disease-specific death. In this study, we analyzed the predictive value of elevated nuclear Stat5a/b expression in PCas treated by radical prostatectomy or active surveillance. The critical role of Stat5a/b in promotion of PCa growth and progression has been well-documented in preclinical PCa models. Specifically, Stat5a/b is critical for prostate cancer cell viability in vitro and for prostate tumor growth in vivo, and Stat5a/b promotes metastatic dissemination of prostate cancer in nude mice. Here, we demonstrate that in intermediate Gleason score PCas treated by radical prostatectomy, high levels of nuclear Stat5a/b predicted both early recurrence (univariate analysis; p<0.0001, multivariate analysis; HR=0.55, p=0.017) and early PCa-specific death (univariate analysis; p=0.028). In addition, high nuclear Stat5a/b predicted early disease recurrence in both univariate (p<0.0001) and multivariate (HR=0.62; p<0.01) analysis in the entire cohort of patients treated by radical prostatectomy (n=562) regardless of the Gleason score. In the second group of patients treated by active surveillance, elevated nuclear Stat5a/b expression was associated with early PCa-specific death (p=0.0453) by univariate analysis (Cox regression analysis: 60% increased risk of death, p=0.034). If confirmed in future prospective studies, nuclear Stat5a/b may become a useful independent predictive marker of recurrence of lethal PCa after radical prostatectomy for intermediate Gleason score PCas.

Citation Format: Tuomas Mirtti, Benjamin E. Leiby, Pär Stattin, Anders Bergh, Marja T. Nevalainen, Junaid Abdulghani, Miia Pavela, Elina Aaltonen, Anita Mamtani, Kalle A. Alanen, Lars Egevad, Torvald Granfors, Andreas Josefsson. Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C41.
Abstract C43: Prognostic value of hypoxia-associated genes in prostate cancer
Authors: Gomez Christian R. , Vuk-Pavlovic Stanimir , Kosari Farhad , Munz Jan Marie , Schreiber Claire , Knutson Gaylord , Charlesworth Cristine , Karnes R. Jeffrey , Cheville John , Vasmatzis George
Published: May 2013

Tumor-associated hypoxia has been associated with malignant progression, metastasis and resistance to therapy. We studied the role of oxygen tension (pO2) in modulating the properties of cultured human prostate cancer (CaP) cells. In air, where oxygen tension (pO2) is approximately 20 kPa, cultured CaP cells expressed lower levels of transcripts associated with cancer and urologic disease; reducing pO2 to 2 kPa made these levels comparable to those in surgical CaP specimens suggesting that hypoxically cultured cells, rather than normoxically cultured cells, express genes at levels akin to those in tumor cells in situ. In human primary CaP tissue, transcripts of hypoxia-associated genes DLG7, CCNB1 and HMMR were overexpressed and associated with Gleason score and disease prognosis; this implies the potential prognostic value of these transcripts. While hypoxia affected the CaP cell proteome mostly quantitatively, it did affect expression of tumor–associated antigens and suggested the potential therapeutic relevance of the hypoxic antigenic landscape. Overall, our results suggest that hypoxia modifies cellular properties of cultured CaP cells towards a phenotype more similar to tumor cells in situ. Introduction of pO2 as a variable can constitute a tool for the identification of more effective prognostic biomarkers and development of better therapy for CaP and, possibly, other tumors.

Citation Format: Christian R. Gomez, Stanimir Vuk-Pavlovic, Farhad Kosari, Jan Marie Munz, Claire Schreiber, Gaylord Knutson, Cristine Charlesworth, R. Jeffrey Karnes, John Cheville, George Vasmatzis. Prognostic value of hypoxia-associated genes in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C43.
Abstract C5: Role of ID4 in the development of prostate in mouse
Authors: Sharma Pankaj , Nagappan Peri , Israel Mark A. , Chaudhary Jaideep
Published: May 2013

Introduction: The helix-loop-helix (HLH) family of transcriptional regulatory proteins are key players in a wide array of developmental processes. Studies in mice have convincingly demonstrated that HLH proteins are intimately involved in developmental events such as cellular differentiation and proliferation. The Id1, Id2, Id3 and Id4 gene products are closely related in their HLH regions and show similar affinities for the various E proteins but differ in their expression patterns. The function of Id proteins has recently been addressed by using a gene targeting approach in mice. Previous studies showed that Id1 null mutant mice do not exhibit abnormalities whereas reports from Id4−/− mice, found that Id4 is required for normal brain size, and regulates lateral expansion of the proliferative zone in the developing cortex and hippocampus. We have recently shown that Id4 is highly expressed in the normal human prostate, whereas its expression is epigenetically silenced in prostate cancer. However its role in normal prostate development and function is not known. Here, we demonstrate a role of Id4 in prostate development, by immunohistochemical techniques in Id4−/− mice.

Experimental procedures: To investigate the precise role of Id4 in cellular proliferation and development, normal H&E staining is performed on wild type and Id4−/− mouse prostate tissue. Expression of Id1, AR (Androgen receptor) and NKX3.1 on wild type and Id4−/− mouse prostate tissue was assessed by Immunohistochemistry.

Results: There was no change in expression of Id1 in wild type and Id4−/− mouse prostate. Androgen receptor and NKX3.1 expression in wild type mouse was mostly nuclear but there is no expression was observed in Id4−/− mouse prostate tissue. H&E staining of wild type and Id4−/− mouse prostate indicated a significant difference in the cellular morphology of Id4−/− mouse prostate tissue as compared to the wild type mouse prostate. In addition to cellular morphological changes, the size of androgen dependent reproductive tract organs such as seminal vesicle and prostate were significantly smaller in Id4−/− as compared to heterozygous and wild type mouse.

Conclusions: These results suggest a severe defect in androgen response pathway and support the role of Id4 in prostate development. Difference in the size of seminal vesicles and prostate in Id4−/− mouse shows the physiological role of Id4 in androgen target organs. Size difference could be due to lack of translocation of AR to nuclei however exact molecular mechanism remains to be investigated.

Acknowledgement: The research was supported by NIH/NCI-RO1CA128914 and in part by NIH/NCRR/RCMI G12RR03062.

Citation Format: Pankaj Sharma, Peri Nagappan, Mark A. Israel, Jaideep Chaudhary. Role of ID4 in the development of prostate in mouse [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C5.
Abstract C55: The basic helix loop helix transcription factor E2A is associated with prostate cancer
Authors: Patel Divya , Chaudhary Jaideep
Published: May 2013

Introduction: E2A (TCF3) is a multifunctional basic helix loop helix (bHLH), transcription factor. E2A regulates transcription of target genes by homo- or heterodimerization with other bHLH proteins such as MyoD, Mash, NeuroD and Id family of helix loop helix proteins. In general, E2A promotes cell differentiation, acts as a negative regulator of cell proliferation in normal cells and cancer cell lines and is required for normal B-cell development. Given the diverse biological pathways regulated/influenced by E2A little is known about its expression in cancer. Data mining approaches suggested that E2A is highly expressed in many cancers including prostate.

Experimental design: E2A protein expression was investigated in clinical prostate tumor samples on high density tissue microarray slides by Immunohistochemistry (IHC). The expression of E2A in PCA cell lines DU145 and PC3 was temporarily silenced using E2A siRNA (sc-35245, Santa Cruz Biotechnology) and its effect on the Proliferation, cell cycle, apoptosis, mitochondrial membrane potential and caspase 3/7 activation was determined. The underlying mechanism of action of E2A was investigated by analyzing the expression of potential E2A regulated genes involved in cell cycle.

Results: Consistent with increased E2A expression in prostate cancer suggested by meta-analysis, the E2A immunohistochemistry performed on prostate tissue microarrays demonstrated increased E2A expression in prostate cancer as compared to normal prostate. Silencing of E2A in prostate cancer cells DU145 and PC3 led to a significant reduction in proliferation due to G1 arrest that was in part mediated by increased CDKN1A(p21) and decreased Id1, Id3 and c-myc. E2A silencing in prostate cancer cell lines also resulted in increased apoptosis due to decrease in mitochondrial membrane permeability and increase in caspase 3/7 activity.

Conclusion: Based on our results, we propose that E2A could be an upstream regulator of Id1 and c-Myc which are highly expressed in prostate cancer. These results for the first time demonstrate that E2A could in fact acts as a tumor promoter at least in prostate cancer.

Acknowledgements: This study was supported by NIH/NCI RO1 CA128914 and NIH/NCRR/RCMI G12RR03062.

Citation Format: Divya Patel, Jaideep Chaudhary. The basic helix loop helix transcription factor E2A is associated with prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C55.
Abstract C65: Drug-tolerant cancer cells show reduced tumor-initiating capacity: Depletion of CD44+ cells and evidence for epigenetic mechanisms
Authors: Chen Xin , Fokt Izabela , Skora Stanislaw , Priebe Waldemar , Bi Yongyi , Tang Dean G. , Yan Hong , Zhang Qiuping , Qin Jichao , Li Hangwen , Liu Can , Davis Tammy , Coletta Luis D. , Klostergaard Jim
Published: May 2013

Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide, paclitaxel and some experimental drugs (i.e., staurosporine and 2 paclitaxel analogs), which led to populations of drug-tolerant cells (DTCs). Surprisingly, these DTCs, when implanted either subcutaneously or orthotopically into NOD/SCID mice, exhibited much reduced tumorigenicity or were even nontumorigenic. Drug-tolerant DLD1 colon cancer cells selected by a similar chronic selection protocol also displayed reduced tumorigenicity whereas drug-tolerant UC14 bladder cancer cells demonstrated either increased or decreased tumor-regenerating capacity. Drug-tolerant Du145 cells demonstrated low proliferative and clonogenic potential and were virtually devoid of CD44+ cells. Prospective knockdown of CD44 in Du145 cells inhibited cell proliferation and tumor regeneration whereas restoration of CD44 expression in drug-tolerant Du145 cells increased cell proliferation and partially increased tumorigenicity. Interestingly, drug-tolerant Du145 cells showed both increases and decreases in many ‘stemness’ genes. Finally, evidence was provided that chronic drug exposure generated DTCs via epigenetic mechanisms involving molecules such as CD44 and KDM5A. Our results thus reveal that 1) not all DTCs are necessarily CSCs; 2) conventional chemotherapeutic drugs such as taxol and etoposide may directly target CD44+ tumor-initiating cells; and 3) DTCs generated via chronic drug selection involve epigenetic mechanisms.

Citation Format: Xin Chen, Izabela Fokt, Stanislaw Skora, Waldemar Priebe, Yongyi Bi, Dean G. Tang, Hong Yan, Qiuping Zhang, Jichao Qin, Hangwen Li, Can Liu, Tammy Davis, Luis D. Coletta, Jim Klostergaard. Drug-tolerant cancer cells show reduced tumor-initiating capacity: Depletion of CD44+ cells and evidence for epigenetic mechanisms [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C65.
Abstract PR2: Optimization and applications of a tissue slice culture model of the normal and malignant human prostate
Authors: Maund Sophia Lisette , Nolley Rosalie , Peehl Donna
Published: May 2013

Current in vitro and in vivo models for prostate cancer do not accurately recapitulate many critical aspects of prostate cancer biology. In vitro cell culture systems lack tissue architecture, complex cellular interactions, and the prostate microenvironment. Neither xenograft nor transgenic models generate authentic prostate pathobiology, and genetic and molecular fidelity is often a concern both in vitro and in vivo. Ex vivo organotypic culture systems have been used as valuable research models for several tissue types. Our lab has recently established a tissue slice graft model for prostate cancer in vivo using precision-cut 300 micron slices of radical prostatectomy tissue implanted under the mouse renal capsule. We have also developed a complimentary in vitro tissue slice culture (TSC) model that we have used for a variety of studies, including evaluation of the DNA damage response in normal cell types of the prostate. The main challenges for normal prostate TSC are maintaining luminal cell integrity beyond 48 hours and preventing hyperproliferation of basal cells. Less is known about the maintenance of cancer in TSCs. We have compared several culture conditions and can maintain normal prostate structure and function up to 4 days using PFMR-4A media supplemented with cholera toxin, epidermal growth factor, bovine pituitary extract, phosphoethanolamine, hydrocortisone, selenium, gentamycin, retinoic acid, insulin, vitamin E, and androgen R1881. Dose-response and time-course experiments revealed that the optimal concentration of R1881 for luminal cell integrity is 50nM. We verified expression of luminal and basal cell-specific markers by immunofluorescence of frozen sections, and we observed secretion of PSA by ELISA.

In addition, confocal microscopy is a useful technology for visualizing the 3-dimensional architecture of TSCs. With robust survival of TSCs up to 4 days in vitro, we have a wide range of ongoing and future experimental directions including drug delivery and cell targeting, invasion and migration studies, and metabolic and molecular profiling. Furthermore, we are poised for collaboration with those who want to test their experimental methods in an intact prostate cancer model in vitro. The prostate TSC model is undoubtedly more authentic than current in vitro models, and we are optimizing its utility with the goal of executing more realistic pre-clinical studies.

This abstract is also presented as Poster A69.

Citation Format: Sophia Lisette Maund, Rosalie Nolley, Donna Peehl. Optimization and applications of a tissue slice culture model of the normal and malignant human prostate [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr PR2.
ACCF/AHA/SCAI 2013 Update of the Clinical Competence Statement on Coronary Artery Interventional Procedures
Authors: Harold John G. , Bass Theodore A. , Bashore Thomas M. , Brindis Ralph G. , Brush John E. , Burke James A. , Dehmer Gregory J. , Deychak Yuri A. , Jneid Hani , Jollis James G. , Landzberg Joel S. , Levine Glenn N. , McClurken James B. , Messenger John C. , Moussa Issam D. , Muhlestein J. Brent , Pomerantz Richard M. , Sanborn Timothy A. , Sivaram Chittur A. , White Christopher J. , Williams Eric S. ,   Presidents and Staff,   American College of Cardiology Foundation, Harold John G. , Jacobovitz Shalom , Oetgen William J. , May Charlene L. , Phoubandith Dawn R. , Ronan Grace D. , Barrett Erin A. ,   American Heart Association, Arnett Donna , Brown Nancy , Robertson Rose Marie , Whitman Gayle R. , Bezanson Judy L. ,   Society of Cardiovascular Angiography and Interventions, Bass Theodore A. , Linsky Norm , Harder Joel
Published: May 2013

Supplemental Digital Content is available in the text.
Questing for Circadian Dependence in ST-Segment–Elevation Acute Myocardial Infarction
Authors: Ammirati Enrico , Cristell Nicole , Cianflone Domenico , Vermi Anna-Chiara , Marenzi Giancarlo , De Metrio Monica , Uren Neal G. , Hu Dayi , Ravasi Timothy , Maseri Attilio , Cannistraci Carlo V.
Published: May 2013

Rationale:

Four monocentric studies reported that circadian rhythms can affect left ventricular infarct size after ST-segment–elevation acute myocardial infarction (STEMI).

Objective:

To further validate the circadian dependence of infarct size after STEMI in a multicentric and multiethnic population.

Methods and Results:

We analyzed a prospective cohort of subjects with first STEMI from the First Acute Myocardial Infarction study that enrolled 1099 patients (ischemic time <6 hours) in Italy, Scotland, and China. We confirmed a circadian variation of STEMI incidence with an increased morning incidence (from 6:00 am till noon). We investigated the presence of circadian dependence of infarct size plotting the peak creatine kinase against time onset of ischemia. In addition, we studied the patients from the 3 countries separately, including 624 Italians; all patients were treated with percutaneous coronary intervention. We adopted several levels of analysis with different inclusion criteria consistent with previous studies. In all the analyses, we did not find a clear-cut circadian dependence of infarct size after STEMI.

Conclusions:

Although the circadian dependence of infarct size supported by previous studies poses an intriguing hypothesis, we were unable to converge toward their conclusions in a multicentric and multiethnic setting. Parameters that vary as a function of latitude could potentially obscure the circadian variations observed in monocentric studies. We believe that, to assess whether circadian rhythms can affect the infarct size, future study design should not only include larger samples but also aim to untangle the molecular time–dynamic mechanisms underlying such a relation.
Female Mystics in Mediaeval Islam: The Quiet Legacy
Authors: Azad Arezou
Published: May 2013

Abstract

Historians and analysts of current affairs alike are interested in the role that women have played in Islam, including the extent to which women were the agents and creators of Islamic mysticism. We still know surprisingly little about premodern learned women, particularly from the eastern Iranian world. This article describes one female mystic, Umm ʿAlī, who flourished in ninth-century Balkh and has so far eluded modern scholarship. A historiographical study of her provides insight into how the representations of mystical women changed over time. From the earlier sources, we learn that Umm ʿAlī applied creative and interesting strategies that provided her access to the highest sources of learning. Umm ʿAlī’s case also allows for some tentative conclusions on the importance of pedigree, and the practice of strategic marriages that connect local power-holders with the ʿulamāʾ.
Continuing the Stolen Generations: Child Protection Interventions and Indigenous People
Authors: Douglas Heather , Walsh Tamara
Published: May 2013

Indigenous Australian children are significantly over-represented in out of home care. Figures evidencing this over-representation continue to increase at a startling rate. Similar experiences have been identified among native peoples in Canada, the United States and New Zealand. Drawing on interviews with lawyers who work with Indigenous parents in child protection matters in Queensland, Australia, this article examines how historical factors, discriminatory approaches and legal structures and processes contribute to the high rates of removal and, we argue, to the perpetuation of the stolen generations.
Thirteen new species of the spider genus Karaops (Araneae: Selenopidae) from Western Australia
Authors: CREWS SARAH C.
Published: May 2013

Thirteen new species of the recently-described genus Karaops Crews and Harvey, 2011 are described from Western Aus-tralia, bringing the total number of species of this genus to 37. The new species are K. umiida sp. nov. (♀,♂), K. nyiyaparli sp. nov. (♀), K. kariyarra sp. nov. (♀), K. yurlburr sp. nov. (♀,♂), K. feedtime sp. nov. (♀), K. forteyi sp. nov. (♀,♂), K. yindjibarndi sp. nov. (♂), K. jaburrara sp. nov. (♂), K. ngarluma sp. nov. (♂), K. nyangumarta sp. nov. (♀,♂), K. nyamal sp. nov. (♀), K. banyjima sp. nov. (♀) and K. yumbu sp. nov. (♂). The male of K. martamarta Crews and Harvey, 2011 is described for the first time, and new distribution records are given for this species and for K. burbidgei Crews and Har-vey, 2011. Finally, a new key to all of the described species of Karaops is provided.
A new species of Megaesthesius Rathbun, 1909 (Crustacea: Brachyura: Chasmocarcinidae) from deep water off Western Australia
Authors: DAVIE PETER J.F.
Published: May 2013

A new species of Megaesthesius Rathbun, 1909, M. westralia, is described from shelf waters off Western Australia. It can be separated from its two congeners by differences in carapace shape and dentition, as well as differences in the male ab-domens and gonopods.
New apterous Carventinae from Sri Lanka and Southern India (Hemiptera: Heteroptera: Aradidae)
Authors: HEISS ERNST , BAŇAŘ PETR
Published: May 2013

Two new species of apterous Carventinae are described in this paper. One belongs to the endemic monotypic genus Singhalaptera Heiss 2001 from Sri Lanka (Singhalaptera secunda n.sp.), and the other to the monotypic genus Signocoris Hoberlandt 1958 from Madras (Signocoris nilgiricus n.sp.). All four known species of both genera are illustrated and compared.
Advertisement call of Scinax strigilatus (Spix, 1824) (Anura: Hylidae) from southern Bahia, Brazil
Authors: MENDES CAIO VINICIUS DE MIRA , JUNIOR EUVALDO MARCIANO , RUAS DANILO SILVA , DE OLIVEIRA RENAN MANOEL , SOLÉ MIRCO
Published: May 2013

Scinax strigilatus (Spix, 1824) is a member of the Scinax catharinae species group that inhabits forested streams in the Atlantic Rainforest of southern Bahia, northeastern Brazil. The loss of the holotype resulted in years of nomenclatural confusion solved with the designation of a neotype and the redescription of the species by Pimenta et al. (2007). Aiming to contribute to the taxonomic status and natural history of the species, we describe herein the advertisement call of Scinax strigilatus (Fig. 1A).
Climate Change from 1850 to 2005 Simulated in CESM1(WACCM)
Authors: Marsh Daniel R. , Mills Michael J. , Kinnison Douglas E. , Lamarque Jean-Francois , Calvo Natalia , Polvani Lorenzo M.
Published: May 2013

The NCAR Community Earth System Model (CESM) now includes an atmospheric component that extends in altitude to the lower thermosphere. This atmospheric model, known as the Whole Atmosphere Community Climate Model (WACCM), includes fully interactive chemistry, allowing, for example, a self-consistent representation of the development and recovery of the stratospheric ozone hole and its effect on the troposphere. This paper focuses on analysis of an ensemble of transient simulations using CESM1(WACCM), covering the period from the preindustrial era to present day, conducted as part of phase 5 of the Coupled Model Intercomparison Project. Variability in the stratosphere, such as that associated with stratospheric sudden warmings and the development of the ozone hole, is in good agreement with observations. The signals of these phenomena propagate into the troposphere, influencing near-surface winds, precipitation rates, and the extent of sea ice. In comparison of tropospheric climate change predictions with those from a version of CESM that does not fully resolve the stratosphere, the global-mean temperature trends are indistinguishable. However, systematic differences do exist in other climate variables, particularly in the extratropics. The magnitude of the difference can be as large as the climate change response itself. This indicates that the representation of stratosphere–troposphere coupling could be a major source of uncertainty in climate change projections in CESM.
Estuary Classification Revisited
Authors: Guha Anirban , Lawrence Gregory A.
Published: May 2013

Studies over a period of several decades have resulted in a relatively simple set of equations describing the tidally and width-averaged balances of momentum and salt in a rectangular estuary. The authors rewrite these equations in a fully nondimensional form that yields two nondimensional variables: (i) the estuarine Froude number and (ii) a modified tidal Froude number. The latter is the product of the tidal Froude number and the square root of the estuarine aspect ratio. These two variables are used to define a prognostic estuary classification scheme, which compares favorably with published estuarine data.
Bad Jobs, Bad Health? How Work and Working Conditions Contribute to Health Disparities
Authors: Burgard Sarah A. , Lin Katherine Y.
Published: May 2013

In this review, we touch on a broad array of ways that work is linked to health and health disparities for individuals and societies. First focusing on the health of individuals, we discuss the health differences between those who do and do not work for pay, and review key positive and negative exposures that can generate health disparities among the employed. These include both psychosocial factors like the benefits of a high-status job or the burden of perceived job insecurity, as well as physical exposures to dangerous working conditions like asbestos or rotating shift work. We also provide a discussion of the ways differential exposure to these aspects of work contributes to social disparities in health within and across generations. Analytic complexities in assessing the link between work and health for individuals, such as health selection, are also discussed. We then touch on several contextual-level associations between work and the health of populations, discussing the importance of the occupational structure in a given society, the policy environment that prevails there, and the oscillations of the macroeconomy for generating societal disparities in health. We close with a discussion of four areas and associated recommendations that draw on this corpus of knowledge but would push the research on work, health, and inequality toward even greater scholarly and policy relevance.
Health-Related Quality of Life Among Patients With Peripheral Arterial Disease
Authors: Maksimovic Milos , Vlajinac Hristina , Marinkovic Jelena , Kocev Nikola , Voskresenski Tatjana , Radak Djordje
Published: May 2013

We evaluated health-related quality of life (HRQoL) among patients with peripheral arterial disease (PAD) and compared the results with those of the general population. We also evaluated the possible association between some demographic and clinical characteristics of patients with PAD and HRQoL. A cross-sectional study involved 102 consecutive patients with verified PAD referred to the Dedinje Vascular Surgery Clinic in Belgrade. The HRQoL was measured using Medical Outcome Survey Short Form 36 (SF-36). Patients with PAD had significantly lower mean SF-36 scores for physical functioning, role-physical, bodily pain, social functioning, role-emotional, and mental health in comparison with the general population. The HRQoL was significantly more impaired in patients with severe PAD. Patients with PAD had a reduced HRQoL compared with the general population. The impact of PAD on HRQoL was independent of other factors related to both the disease and the HRQoL.
Admission Hyperglycemia Predicts Inhospital Mortality and Major Adverse Cardiac Events After Primary Percutaneous Coronary Intervention in Patients Without Diabetes mellitus
Authors: Ekmekci Ahmet , Cicek Gokhan , Uluganyan Mahmut , Gungor Baris , Osman Faizel , Ozcan Kazim Serhan , Bozbay Mehmet , Ertas Gokhan , Zencirci Aycan , Sayar Nurten , Eren Mehmet
Published: May 2013

Admission hyperglycemia is associated with high inhospital and long-term adverse events in patients that undergo primary percutaneous coronary intervention (PCI). We aimed to evaluate whether hyperglycemia predicts inhospital mortality. We prospectively analyzed 503 consecutive patients. The patients were divided into tertiles according to the admission glucose levels. Tertile I: glucose <118 mg/dL (n = 166), tertile II: glucose 118 to 145 mg/dL (n = 168), and tertile III: glucose >145 mg/dL (n = 169). Inhospital mortality was 0 in tertile I, 2 in tertile II, and 9 in tertile III ( P < .02). Cardiogenic shock occurred more frequently in tertile III compared to tertiles I and II (10% vs 4.1% and 0.6%, respectively, P = .01). Multivariate logistic regression analysis revealed that patients in tertile III had significantly higher risk of inhospital major adverse cardiac events compared to patients in tertile I (odds ratio: 9.55, P < .02). Admission hyperglycemia predicts inhospital adverse cardiac events in mortality and acute ST-segment elevation myocardial infarction in patients that underwent primary PCI.
Anxiety Score as a Risk Factor for Radial Artery Vasospasm During Radial Interventions
Authors: Ercan Suleyman , Unal Ahmet , Altunbas Gokhan , Kaya Hilal , Davutoglu Vedat , Yuce Murat , Ozer Orhan
Published: May 2013

We determined the role of anxiety level on radial artery spasm during transradial coronary angiography. Eighty-one patients who had an indication for coronary angiography were enrolled. Radial artery vasospasm was determined by addressing 5 signs: persistent forearm pain, pain response to catheter manipulation, pain response to sheath withdrawal, difficult catheter manipulation after being “trapped” by the radial artery, and considerable resistance on withdrawal of sheath. Radial spasm defined as at least 2 of the 5 signs. The Hamilton Anxiety scale questionnaire was used to determine the level of anxiety. Vasospasm was observed in 19.1% of the patients. Anxiety score was significantly higher in women (11.1 ± 7.2 vs 17.6 ± 7.3; P < .001). Vasospasm was significantly correlated with female sex ( P < .001, r = .43) and anxiety score ( P = .007, r = .29). Female sex was associated with higher anxiety scores ( P < .001, r = .43). In conclusion, higher anxiety scores and female sex are important risk factors for radial artery vasospasm.
Neutrophil-to-Lymphocyte Ratio is Associated With Severity of Coronary Artery Ectasia
Authors: Sarli Bahadir , Baktir Ahmet Oguz , Saglam Hayrettin , Arinc Huseyin , Kurtul Serkan , Sivgin Serdar , Akpek Mahmut , Kaya Mehmet G.
Published: May 2013

We investigated the association between coronary artery ectasia (CAE) and Neutrophil-to-lymphocyte ratio (NLR), an indicator of the inflammatory state. The study population included 434 patients (247 males, mean age 62 ± 10 years) including 230 patients with isolated CAE and 104 patients with coronary artery disease and 100 patientss with normal coronary arteries. The NLR was measured at admission and 30 days after coronary angiography in all the patients. The NLR was significantly higher in patients with CAE than those with normal coronary arteries (2.2 ± 0.6-1.3 ± 0.6, P < .001). Linear regression analyses revealed that NLR (coefficient β = −.61, P < .001) was significantly associated with severity of CAE. The NLR is significantly higher in patients with CAE compared to controls with normal coronary arteries, and NLR is associated with severity of CAE.
Teacher Unions in Political Transitions: The South African Democratic Teachers’ Union (SADTU) and the Dying Days of Apartheid, 1990–1993
Authors: Amoako Samuel
Published: May 2013

The negotiation to end apartheid – which was initiated in secret in the 1980s – solidified in the 1990s when FW de Klerk unbanned the African National Congress (ANC), South African Communist Party (SACP), Pan African Congress (PAC) and other political and social movements, as well as struggle icons, prominent among whom was Mandela. The South African Democratic Teachers’ Union (SADTU) emerged within the euphoria surrounding Mandela’s release and the negotiations to end apartheid. SADTU combined its educational struggles with the political struggle to end apartheid rule. Drawing on documentary (mainly archival), newspaper reports and oral evidence, this article examines SADTU’s struggles for recognition, its resistance against education restructuring, and its defiance campaign against inspection from 1990–1993. I suggest that SADTU’s contentions during the period were rooted in the political struggle to end apartheid rule since it regarded the apartheid education departments as illegitimate structures needing to be dismantled. In addition, the socio-economic undercurrents that characterized the transition were carried into education restructuring and thus pushed SADTU into militancy.
The Moderating Influence of Narrative Causality as an Untapped Pool of Variance for Narrative Persuasion
Authors: Dahlstrom Michael F.
Published: May 2013

This study examines if accounting for the causal location of information within a narrative can improve the predictability of narrative persuasion. Using perceived realism as a variable of narrative persuasion and environmental communication as a context, results reveal a significant moderating influence of the location of information relative to the cause-and-effect structure of the narrative. Specifically, external realism increased the acceptance of narrative information, but only after accounting for the additional variance of location and only for the subset of information on the causal line of the narrative. Future studies should continue to explore how the variance associated with this narrative causality can be leveraged toward a more nuanced understanding of narrative persuasion.
Attenders Versus Slackers
Authors: Stellmack Mark A.
Published: May 2013

Studies of the effects of class attendance on class performance typically are quasi-experimental because students choose whether or not to attend class; that is, the samples are self-selecting. The lack of random assignment prevents one from establishing a causal relationship between attendance and performance. Relating attendance to performance using the students in a research methods class, regardless of whether the data show a significant relationship, can serve as the basis of a discussion of quasi experiments and the alternative explanations that are inherent in their design. This article gives suggestions for presenting and discussing the data.