bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A38: Maternal embryonic leucine zipper kinase (MELK) is upregulated in high-grade prostate cancer
Authors: Kuner Ruprecht , Sültmann Holger , Fälth Maria , Pressinotti Nicole Chui , Brase Jan Christoph , Balaguer-Puig Sabrina , Schäfer Georg , Bartsch Georg , Steiner Eberhard , Klocker Helmut 
Published: May 2013

Abstract
Loss of cell cycle control is a prerequisite for cancer onset and progression. In prostate cancer, increased activity of cell cycle proliferating genes has been associated with prognostic parameters such as biochemical relapse and survival. The identification of novel oncogenic and druggable targets in patient subgroups with poor prognosis may help to develop targeted therapy approaches.
We analyzed prostate cancer and corresponding benign tissues (n = 98) using microarrays. The comparison of high and low grade tumors (Gleason score ≥ 4+3 vs. ≤ 3+4) revealed 144 differentially expressed genes (p &lt; 0.05), which are associated with a severe disease course. Out of these, 15 genes are assigned to cell cycle process. The gene maternal embryonic leucine zipper kinase (MELK) was identified to be highly correlated with cell cycle and prostate cancer associated genes like UBE2C, TOP2A, CCNB2 and AURKB, and was therefore further included into validation and functional experiments. The association between MELK gene expression and high-risk prostate cancer was validated in an independent patient cohort (p &lt; 0.005, n = 79). Furthermore, our finding was supported by a public microarray dataset showing a higher MELK expression in prostate cancer patients with biochemical relapse. Immunohistochemical analysis using a tissue microarray (n = 94) revealed increased MELK protein expression in prostate cancer tissues of high Gleason scores. Knockdown of MELK decreased cell viability in PC3 and LNCaP cells. Microarray analysis upon MELK knockdown experiments revealed downstream processes like chromatin modification, embryonic development and cell migration. Our findings indicate that the protein serine/threonine kinase MELK represents a promising marker for advanced prostate cancer disease.
Citation Format: Ruprecht Kuner, Holger Sültmann, Maria Fälth, Nicole Chui Pressinotti, Jan Christoph Brase, Sabrina Balaguer-Puig, Georg Schäfer, Georg Bartsch, Eberhard Steiner, Helmut Klocker. Maternal embryonic leucine zipper kinase (MELK) is upregulated in highgrade 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 A38.
Abstract A44: Practical habit and herbalism knowledge for prostate cancer-related problems among Bangladeshi immigrants to the United States: The experience of Bronx borough in New York City
Authors: Mollik Md. Ariful Haque , Trainor Douglas James 
Published: May 2013

Abstract
In the United States, herbalism use is most prevalent among the immigrants. Very few studies have been conducted in the Bangladeshi immigrants to the United States of America on herbalism knowledge. Therefore a gap in knowledge exists. This study deals with the field observations recorded on the therapeutic applications of the herbalism used in prostate cancer related problems by the Bangladeshi immigrants of Bronx borough in the New York City. Fieldwork was carried out from August 2011 to November 2011. Semi structured interviews and guided field-walk methods were used to gather information on herbalism used by the Bangladeshi immigrants. Along with herbalism, information was also collected on herbalism parts used, formulations, and dosages. Information on phytochemicals as well as pharmacologic activity studies on this herbalism (if any) was obtained from several data bases. The collected information indicates that the following herbalism is used to treat prostate-cancer related problems: Swertia chirata Buch.-Ham. ex Wall., Zingiber officinale Roscoe, Citrus aurantiifolia (Christm.) Swingle, Aloe vera (L.) Burm.f., Plantago major L., Cocos nucifera L., Apis dorsata Fabricius, Allium sativum L., Ocimum gratissimum L., Saccharum officinarum L., Allium cepa L., Momordica charantia L., Areca catechu L., Piper nigrum L., Nigella sativa L., Lactuca sativa L., Ipomoea aquatica Forssk., Persea americana Mill., Panax ginseng C.A.Mey., Carica papaya L., Piper betle L., Bryophyllum pinnatum (Lam.) Oken, Ficus racemosa L., Azadirachta indica A.Juss., Camellia sinensis (L.) Kuntze, Citrullus lanatus (Thunb.) Matsum. & Nakai, Solanum melongena L., Ananas comosus (L.) Merr., Ophicephalus striatus Bloch, Zea mays L., Borassus flabellifer L., Cucumis sativus L., Vigna mungo (L.) Hepper, Brassica napus L., Amaranthus tricolor L., and Aegle marmelos (L.) Corrêa. This study further highlighted the importance of gathering such ethnopharmacology information for effective conservation of the Bangladeshi immigrants' medicinal knowledge and medicinally important herbalism. It is important that modern scientific studies be conducted on this herbalism towards isolation and identification of compounds through which multi-drug resistant prostate cancer related problems can be effectively treated.
Note: This abstract was not presented at the conference because the presenter was unable to attend.
Citation Format: Md. Ariful Haque Mollik, Douglas James Trainor. Practical habit and herbalism knowledge for prostate cancer-related problems among Bangladeshi immigrants to the United States: The experience of Bronx borough in New York City [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 A44.
Abstract A70: PTEN loss induces selective upregulation of CXCL8 signaling to modulate survival and resistance to radiation
Authors: Coulter Jonathan , Maxwell Pamela , McKechnie Melanie , Neisen Jessica , Kennedy Richard , Salto-Tellez Manuel , Albanese Chris , Waugh David 
Published: May 2013

Abstract
PTEN is a haplo-insufficient tumor suppressor and the most frequently mutated gene in prostate cancer (CaP). Moreover, loss of PTEN expression arising from allele deletion or promoter methylation is prevalent early disease. The objective of our study was to characterize how the genetic instability and/or stress-induced signaling arising from PTEN loss modulated the expression of clinically-relevant pro-inflammatory chemokines. Transient (siRNA) or prolonged (shRNA) repression of PTEN resulted in increased transcription-mediated increases in expression of CXCL8 and its receptors, CXCR1 and CXCR1 in DU145 and 22Rv1 cells. Stress-induced expression of CXCL8, CXCR1 and CXCR2 was greater in magnitude and duration in PTEN-null PC3 and LNCaP cells, in contrast to the dampened response observed in PTEN-expressing cells. PTEN had no effect on basal or stress-induced expression of CCL2, CXCL12 or their receptors in prostate cancer cells. Moroever, the efficacy of autocrine CXCL8 signaling to induce HIF-1 and NF-κB transcription was also greater in magnitude and duration in PTEN-null prostate cancer cells or following siRNA-mediated PTEN knockdown in DU145 and 22Rv1 cells. Consistent with in vitro data, we observed increased expression of the orthologous murine chemokine KC in atypical cytological features of PTEN+/− prostate tissue relative to normal epithelium in PTENWT glands. Finally, siRNA or shRNA-mediated attenuation of CXCL8 signaling selectively decreased the viability of CaP cells harboring partial or complete PTEN-loss. Furthermore, the knockdown of CXCL8 signaling potentiated the sensitivity of PTEN-depleted prostate cancer cells to clinicallyrelevant doses of ionozing radiation. We conclude that there is a selective upregulation of CXCL8 signaling in PTEN-deficient prostate epithelium, which contributes to the growth, survival and reduced therapeutic sensitivity of these cells.
Citation Format: Jonathan Coulter, Pamela Maxwell, Melanie McKechnie, Jessica Neisen, Richard Kennedy, Manuel Salto-Tellez, Chris Albanese, David Waugh. PTEN loss induces selective upregulation of CXCL8 signaling to modulate survival and resistance to radiation [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 A70.
Abstract B29: A meta-analysis of racial disparities in the association between 8q24 and prostate cancer risk
Authors: Price Douglas K. , Troutman Sarah M. , Sissung Tristan M. , Cropp Cheryl , Venzon David J. , Spencer Shawn D. , Figg William D. 
Published: May 2013

Abstract
Purpose: The aim of this meta-analysis was to elucidate potential racial disparities in the association between single nucleotide polymorphisms (SNPs) and prostate cancer risk.
Background: Racial disparities in the incidence of prostate cancer exist but remain unexplained. Recent studies implicate SNPs within the 8q24 region as risk factors for prostate cancer and the frequency of variant alleles at these SNPs appear to differ by race.
Methods: Twenty-nine studies of seven SNPs and one microsatellite marker located within the 8q24 region were included in the meta-analyses. Allelic odds ratio (OR) values and confidence intervals were calculated using the Mantel-Haenszel test. This test assumes homogeneity so the Breslow-Day test was first used to determine whether or not the assumption of homogeneity was valid in each population.
Results: Prostate cancer risk was associated with the following SNPs in all included races: rs6983267, rs1447295, rs6983561, rs7837688, rs16901979, and DG8S737(-8). However, race-dependent differences were detected in (1) baseline allele frequencies, (2) degree of risk conferred, and (3) predictive power relative to the other SNPs.
Conclusions: The inheritance of 8q24 polymorphisms may in part account for racial disparities in the incidence of prostate cancer.
Citation Format: Douglas K. Price, Sarah M. Troutman, Tristan M. Sissung, Cheryl Cropp, David J. Venzon, Shawn D. Spencer, William D. Figg. A meta-analysis of racial disparities in the association between 8q24 and prostate cancer risk [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 B29.
Abstract B34: IKKalpha regulation of mTORC1 and modulation of prostate tumorigenesis through phosphorylation of mTOR
Authors: Dan Hancai , Baldwin Albert S. 
Published: May 2013

Abstract
The mammalian target of rapamycin (mTOR) is a critical mediator of cell growth, cell proliferation, survival, and energy metabolism. mTOR is activated downstream of growth factors, insulin, and Akt-dependent signaling associated with oncoprotein expression or loss of the tumor-suppressor PTEN. In this regard, mTOR activity is associated with cancer cell growth and survival. Here, we have explored an involvement of the I kappa B kinase (IKK) pathway, associated with nuclear factor-kappaB activation, in controlling mTOR activity. The experiments show that IKK alpha controls mTOR activity in Akt-active, PTEN-null prostate cancer cells by directly phosphorylation of mTOR at Serine 1415. In these cells, IKK alpha associates with mTORC1 and weaken the association between mTOR and Raptor, an important component of mTORC1, to increase mTORC1 kinase activity by phosphorylation in an Akt-dependent manner. Additionally, IKKalpha phosphorylation of mTOR is required for efficient induction of cell proliferation downstream of constitutively active Akt in these cells. The results indicate a novel role for IKKalpha in controlling mTOR function in protate cancer cells with loss of PTEN and constitutive Akt activity.
Citation Format: Hancai Dan, Albert S. Baldwin. IKKalpha regulation of mTORC1 and modulation of prostate tumorigenesis through phosphorylation of mTOR [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 B34.
Abstract B48: Integrin α6 S-nitrosylation induces prostate cancer cell migration by loss of adhesion to laminin-1
Authors: Isaac Jared , Lam Ying Wai , Tarapore Pheruza , Ho Shuk-mei 
Published: May 2013

Abstract
Prostate cancer is the second most common cancer in American males. Elevated nitric oxide and nitric oxide synthase levels are associated with the progression of prostate tumors. S-nitrosylation, a reversible nitric oxide post-translational modification of cysteines, was investigated here. This report showed that low dose nitric oxide and inducible nitric oxide synthase induced the migration of prostate cancer cells, which was blocked using selective integrin alpha 6 and inducible nitric oxide synthase inhibitors. Furthermore, both nitric oxide donor and inducible nitric oxide synthase targeted integrin alpha 6 for S-nitrosylation on cysteine 86 in prostate cancer cells. Nitric oxide reduced prostate cancer cell adhesion to laminin-1 and integrin alpha 6 binding to laminin beta 1 but theses effects were not seen after mutation of cysteine 86 in integrin alpha 6. S-nitrosylation of integrin alpha 6 cysteine 86 ultimately led to increased migration of prostate cancer cells, which is a potential mechanism of prostate cancer metastasis.
Citation Format: Jared Isaac, Ying Wai Lam, Pheruza Tarapore, Shuk-mei Ho. Integrin α6 S-nitrosylation induces prostate cancer cell migration by loss of adhesion to laminin-1 [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 B48.
Abstract B68: The microenvironment decides how prostate tumors respond to castration treatment
Authors: Bergström Sofia Halin , Rudolfsson Stina , Scherdin Tove Dahl , Bergh Anders 
Published: May 2013

Abstract
Although androgen deprivation is the standard therapy for metastatic prostate cancer the mechanisms for the initial response and subsequent relapse are largely unknown. The stroma and vasculature are necessary for castration-induced involution of the normal prostate, and androgen-independent tumors respond to castration when surrounded by normal prostate tissue. This suggests that the microenvironment is highly important for the therapeutic effect of castration.
To further explore this, androgen-sensitive rat prostate tumor cells (Dunning G) were injected into the rat prostate and/or bone marrow (to simulate bone metastasis) and analyzed for response to castration. Tumors in the prostate responded well to castration with decreased tumor size, both in already established tumors and when tumor cells were injected in castrated animals. The size of bone metastases was, however, unaffected by castration. Both groups developed lung metastasis but castration tended to increase rather than decrease pulmonary tumor burden.
To further explore the mechanisms behind this we have established in vitro cell lines from bone metastasis of both castrated and control rats. In our ongoing experiments we are examining if these cells are responsive to castration if instead placed within the prostate environment or if the resistance to therapy has become stable. The response to castration is also further explored in lung metastasis. Our results suggest that the metastatic environment is highly important for the establishment of castration resistant prostate cancer and that the mechanisms behind this need to be further explored.
Citation Format: Sofia Halin Bergström, Stina Rudolfsson, Tove Dahl Scherdin, Anders Bergh. The microenvironment decides how prostate tumors respond to castration treatment [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 B68.
Abstract C10: Tumor necrosis factor is necessary but not sufficient for castration-induced prostate regression
Authors: Davis Jennifer S. , Nastiuk Kent L. 
Published: May 2013

Abstract
TNF, a pro-inflammatory and immune-regulatory cytokine, is a potent apoptotic stimulus in vitro. There are few examples of a physiologic role for TNF induced apoptosis in vivo, but here we describe a novel role for TNF in prostate epithelial cell apoptosis following androgen withdrawal. We demonstrate, using high resolution serial MRI (magnetic resonance imaging) to measure mouse prostate volume changes over time, that castration induced prostate regression is significantly reduced in mice null for either the Tnf or Tnfr1 genes, but not mice deficient for TRAIL or Fas signaling. Wild type mice treated with soluble TNFR2 (to bind TNF and block signaling) prior to castration showed a similar reduction. Additionally, consistent with a paracrine role for TNF in prostate regression, membrane-bound TNF protein and stromal cell specific TNF mRNA levels increase in rat prostate following castration.
Injection of soluble TNF restores normal levels of prostate regression of Tnf −/− mice. Together, these data indicate that uniquely among these extrinsic death signals, TNF is required for castration induced prostate regression. However, wild type mice receiving soluble TNF in the absence of castration do not exhibit prostate regression, indicating that TNF alone is not sufficient, but acts in the context of additional castration induced signals. A preliminary investigation using ALK5 inhibitors prior to castration suggests that TGFβ signaling may also be important. Understanding the physiologic role for TNF, and the interaction with other signaling pathways active in prostate regression following androgen withdrawal may lead to novel therapies for prostate cancer.
Citation Format: Jennifer S. Davis, Kent L. Nastiuk. Tumor necrosis factor is necessary but not sufficient for castration-induced prostate regression [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 C10.
Abstract C3: Receptor tyrosine kinase(s) modulate androgen receptor signaling in castrate-resistant prostate cancer
Authors: Sharma Ankur , Balk Steven P. 
Published: May 2013

Abstract
This study is designed to investigate the mechanisms underlying effects of receptor tyrosine kinase(s) on androgen receptor (AR) in castrate resistant prostate cancer (CRPC). Hormone ablation therapies remain the mainstay of treatment for metastatic prostate cancer, but disease eventually reoccurs as CRPC where AR has been reactivated despite castrate androgen levels. Amongst ways that facilitate restoration of AR activity in CRPC, receptor tyrosine kinases (RTKs) have been reported to activate AR and induce CRPC growth through as of yet unclear mechanisms. Our investigative studies revealed that lapatinib (inhibits Her2/Her3 heterodimer and EGFR) treatment inhibited endogenous AR expression and activity in C4-2 CRPC cells. Lapatinib induced destabilization and proteosomal degradation of the AR with minimal effect on AR mRNA transcript levels. To further investigate if this effect was dependent on Her2/Her3 or EGFR, an EGFR inhibitor erlotinib was used. It produced modest effects on AR, indicating that effects of lapatinib are predominantly through Her2/Her3. As AKT, a serine/threonine kinase, functions downstream of Her2/Her3, we then directly investigated the effects of AKT on AR in CRPC cells. Our studies revealed that inhibition of AKT decreased endogenous AR expression through proteosomal degradation. Moreover AKT inhibition decreased endogenous AR activity and C4-2 cell survival, indicating that AKT positively regulates AR and CRPC growth. As many groups have previously reported conflicting effects of AKT on AR, we are now focused on the molecular basis for this positive effect of AKT on AR expression and function in CRPC. Preliminary studies indicate that AKT inhibition may be decreasing levels of heat shock proteins (Hsp70, Hsp90) that serve as chaperones for cytoplasmic AR, and may by another mechanism be decreasing AR accumulation in the nucleus. We anticipate that these studies will provide a clear mechanistic view of effects of RTKs and AKT on AR in CRPC and highlight molecules that may be targeted for novel therapeutic interventions.
Citation Format: Ankur Sharma, Steven P. Balk. Receptor tyrosine kinase(s) modulate androgen receptor signaling in castrate-resistant 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 C3.
Abstract C31: NAMPT inhibition combined with radiation enhances cell death in a prostate cancer model
Authors: Zerp Shuraila , Triest Baukelien Van , Floot Ben , Vens Conchita , Verheij Marcel 
Published: May 2013

Abstract
Background and purpose: Prostate cancer patients with localized disease can be treated with radiotherapy. In the present study we investigated the complementary effect of NAMPT inhibitor APO866, on the combination with radiation treatment with respect to prostate tumor cell death. APO866 is a highly specific non-competitive inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in the regulation of NAD+ biosynthesis. Inhibition of NAMPT could deplete cellular NAD+. According to literature NAMPT may have a prominent role in prostate cancer development and progression. Interestingly for research purposes, prostate cancer cell lines PC3 and LNCaP solely depend on the NAMPT synthesis route for their NAD recovery. Treatment of prostate cancer cells with a combination of ionizing radiation and APO866 shows an enhancement of cell death in vitro as well as in vivo.
Results: APO866, in nanomolar concentrations, induces a time- and dose-dependent depletion of cellular NAD+ levels in a panel of human tumor cell lines (U937, J16, LNCaP, PC3 and A431). In vitro, under APO866-mediated reduced NAD+ conditions, solid tumor cell lines PC3 and LNCaP show besides a cytotoxic effect also a decrease in clonogenic survival in combination with ionizing radiation (Dose enhancement factor at 10% survival: 1.34 and 1.45 resp.), which was not caused by radiation-induced enhancement of dsDNA breaks as determined by γ-H2AX nuclear foci formation, nor by induction of apoptosis. In vivo experiments with PC3 xenografts, treated with the APO866/radiation combination, show the combination is more effective than APO866 or radiation treatment alone. The time to reach 300% of the initial tumor volume was in the control group 9.5 days, for APO866 treatment 28.6 days, radiation treatment 51.4 days and for the combined APO866/radiation treatment 76.6 days. Only the combination treatment caused complete initial growth regression. No significant toxicity was observed after any of these treatments. Tumors from animals treated with APO866 showed significant reduced NAD+ levels.
Conclusion: NAMPT inhibition through APO866 treatment enhances cell death in combination with radiation in a prostate cancer model. Targeting NAD+ biosynthesis is a promising strategy in combined modality therapy with radiation.
Citation Format: Shuraila Zerp, Baukelien Van Triest, Ben Floot, Conchita Vens, Marcel Verheij. NAMPT inhibition combined with radiation enhances cell death in a prostate cancer model [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 C31.