bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A41: Effect of dietary vitamin D3 and calcium on the growth of androgeninsensitive human prostate tumor in a murine model
Authors: Ray Rahul , Banks Mara , Abuzahra Hilal , Persons Kelly S. , Eddy Vikram J. , Lambert James R. , Holick Michael F. 
Published: May 2013

Abstract
Vitamin D deficiency has been associated with increased risk of prostate cancer in epidemiologic and prospective studies. An association has also been made between high dietary calcium and increased prostate cancer risk. Previous studies have demonstrated that normal prostate cells and some prostate cancer cells have the ability to convert 25(OH)D to 1α,25(OH)2D. This ability along with epidemiological evidence correlating an inverse relationship between serum 25(OH)D levels and prostate cancer risk suggests that vitamin D may be important for prostate cancer prevention. The effect of dietary vitamin D and calcium on the growth of human androgen-insensitive prostate tumor in an athymic mouse model was evaluated. Three factors were considered in evaluating the role of dietary calcium and vitamin D on prostate tumor in our mice model: tumor-growth, elevation of serum calcium and overall growth of the animals (body weight). Immunohistochemical staining and Real Time PCR analysis were performed on tumors to elucidate the molecular mechanism(s) involved in vitamin D regulation of prostate cancer. Tumor-growth was highest in normal calcium, vitamin D deficient diet group (381±59 mm3) while growth in normal calcium, vitamin D sufficient (179±36 mm3), high calcium, vitamin D sufficient (199±25 mm3) and deficient (204±43 mm3) diets were not significantly different from one another. The normal calcium, vitamin D deficient diet had mice that were normo-calcemic compared to the other diet groups though there was no significant difference between groups for the weights of the animals. Proliferative (Ki67) and apoptotic (Caspase 3) staining revealed no significant difference between vitamin D sufficient and deficient diet groups. Additional staining for p21 did not show any difference among the diet groups. Gene analysis for p21, p27 and p53 did not demonstrate altered transcriptional activity in vitamin D sufficient groups. Bax and bcl-2 mRNA expression were both increased in the high calcium, vitamin D deficient diet group. The difference in tumor growth between the normal calcium, vitamin D deficient diet and the other diets suggest an important role of dietary vitamin D as a preventive agent in androgen-insensitive prostate cancer. More in vivo studies are needed to understand the molecular mechanism(s) behind vitamin D's antitumorigenic effects.
Citation Format: Rahul Ray, Mara Banks, Hilal Abuzahra, Kelly S. Persons, Vikram J. Eddy, James R. Lambert, Michael F. Holick. Effect of dietary vitamin D3 and calcium on the growth of androgeninsensitive human prostate tumor in a murine 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 A41.
Abstract A45: Resveratrol inhibits prostate cancer stem cell characteristics by suppressing Wnt, sonic hedgehog, and Notch pathways
Authors: Srivastava Rakesh K. , Rodova Mariana , Fu Junsheng , Nall Dara , Shankar Sharmila 
Published: May 2013

Abstract
The existence of cancer stem cells (CSCs) in prostate cancer has profound implications for cancer prevention and/or treatment. The CSC population resides within the prostate tumor mass and they may be responsible for drug resistance, and for the recurrence of prostate cancer. Therefore, development of novel strategies to target CSCs by nontoxic agent resveratrol is an innovative and novel idea for the management of prostate cancer. Activation of Wnt, sonic hedgehog (Shh) and Notch pathways are required for the growth of numerous tissues and organs and recent evidence indicates that these pathways are often recruited to regulate self-renewal and metastasis of CSCs. The objectives of this study were to examine the molecular mechanisms by which resveratrol, an active compound in grapes and red vine inhibits self-renewal capacity of prostate CSCs. Our data demonstrated that resveratrol inhibited the expression of pluripotency maintaining transcription factors (Nanog, c-Myc and Oct-4), and spheroid formation by prostate CSCs. Inhibition of Nanog by shRNA enhanced the inhibitory effects of resveratrol on self-renewal capacity of CSCs. Resveratrol suppressed cell proliferation and induced apoptosis by inhibiting the expression of Bcl-2 and IAPs, and activating caspase-3. Interestingly, resveratrol also inhibited the transcriptional activities TCF/LEF, Gli and RBP-Jk. Furthermore, resveratrol inhibited epithelial-mesenchymal transition (EMT) by suppressing the expression of Snail, Slug and ZEB1 transcription factors, which correlated with significantly reduced CSC's migration and invasion, suggesting the blockade of signaling involved in early metastasis. In conclusion, resveratrol can inhibit prostate cancer CSC characteristics by suppressing various signal transduction pathways, and can be used for the management of prostate cancer.
Citation Format: Rakesh K. Srivastava, Mariana Rodova, Junsheng Fu, Dara Nall, Sharmila Shankar. Resveratrol inhibits prostate cancer stem cell characteristics by suppressing Wnt, sonic hedgehog, and Notch pathways [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 A45.
Abstract A51: Disruption of Abi1/Hssh3bp1 expression induces prostatic intraepithelial neoplasia in the conditional Abi1/Hssh3bp1 KO mice
Authors: Xiong Xiaoling , Kotula Leszek , Chorzalska Anna , Dubielecka Patrycja , White Julie , Vedvyas Yogindra , Hedvat Cyrus V. , Haimovitz-Friedman Adriana , Koutcher Jason A. , Sawicki Janet A. 
Published: May 2013

Abstract
Prostate cancer is one of the leading causes of cancer-related deaths in the United States and a leading diagnosed non-skin cancer in American men. Genetic mutations underlying prostate cancer tumorigenesis include alterations of tumor suppressor genes. We previously proposed that ABI1/hSSH3BP1 acts as a tumor suppressor gene (Macoska, et al. 2001 Neoplasia 3, 99-104). Here, we tested this hypothesis by searching for ABI1 gene mutations in primary prostate tumors from patients, and by analyzing the consequences of prostate-specific disruption of the mouse Abi1/Hssh3bp1 orthologue. We sequenced the ABI1/hSSH3BP1 gene and identified mutations in 15 out of 44 prostate tumors. Moreover, complementation growth-, proliferation- and xenograft- assays using the LNCaP cell line, which contains the loss-of-function Abi1 mutation, and stably expressed wt ABI gene, were consistent with the tumor suppressor hypothesis. To test the hypothesis further, we disrupted the gene in the mouse prostate by breeding the Abi1 floxed strain with the probasin promoter-driven Cre recombinase strain. Histopathological evaluation of mice indicated development of prostatic intraepithelial neoplasia (PIN) in Abi1/Hssh3bp1 KO mouse as early as the 8th month, but no progression beyond PIN was observed in mice as old as 12 months. Observed decreased levels of E-cadherin, β-catenin, and WAVE2 in mouse prostate suggest abnormal cellular adhesion as the mechanism underlying PIN development due to Abi1 disruption. In summary, this study provides further evidence for the hypothesis that Abi1 down-regulation plays a role in the development of prostate cancer and warrants further investigations of Abi1's role in prostate cancer tumorigenesis.
Citation Format: Xiaoling Xiong, Leszek Kotula, Anna Chorzalska, Patrycja Dubielecka, Julie White, Yogindra Vedvyas, Cyrus V. Hedvat, Adriana Haimovitz-Friedman, Jason A. Koutcher, Janet A. Sawicki. Disruption of Abi1/Hssh3bp1 expression induces prostatic intraepithelial neoplasia in the conditional Abi1/Hssh3bp1 KO mice [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 A51.
Abstract A52: DNA damage responses in different cell types of nonproliferating human prostate tissue
Authors: af Hällstrsöm Taija M. , Taari Kimmo , Ruutu Mirja , Andersson Leif , Laiho Marikki , Jäämaa Sari , Sankila Anna , Rantanen Ville , Koistinen Hannu , Stenman Ulf-Håkan , Zhang Zhewei , Yang Zhiming , De Marzo Angelo M. 
Published: May 2013

Abstract
DNA damage response (DDR) pathways have been extensively studied in cancer cell lines and mouse models, but little is known about how DNA damage is recognized by different cell types in nonmalignant, slowly replicating human tissues. Here, we assess, using ex vivo cultures of human prostate tissue, DDR caused by cytotoxic drugs (camptothecin, doxorubicin, etoposide, and cisplatin) and ionizing radiation (IR) in the context of normal tissue architecture. Using specific markers for basal and luminal epithelial cells, we determine and quantify cell compartment-specific damage recognition. IR, doxorubicin, and etoposide induced the phosphorylation of H2A.X on Ser(139) (gH2AX) and DNA damage foci formation. Surprisingly, luminal epithelial cells lack the prominent gH2AX response after IR when compared with basal cells, although ATM phosphorylation on Ser(1981) and 53BP1 foci were clearly detectable in both cell types. The attenuated gH2AX response seems to result from low levels of total H2A.X in the luminal cells. Marked increase in p53, a downstream target of the activated ATM pathway, was detected only in response to camptothecin and doxorubicin. These findings emphasize the diversity of pathways activated by DNA damage in slowly replicating tissues and reveal an unexpected deviation in the prostate luminal compartment that may be relevant in prostate tumorigenesis. Detailed mapping of tissue and cell type differences in DDR will provide an outlook of relevant responses to therapeutic strategies.
Note: This abstract was not presented at the conference because the presenter was unable to attend.
Citation Format: Taija M. af Hällström, Kimmo Taari, Mirja Ruutu, Leif Andersson, Marikki Laiho, Sari Jäämaa, Anna Sankila, Ville Rantanen, Hannu Koistinen, Ulf-Håkan Stenman, Zhewei Zhang, Zhiming Yang, Angelo M. De Marzo. DNA damage responses in different cell types of nonproliferating human prostate tissue [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 A52.
Abstract A53: Effect of an ERβ agonist in the gerbil senile prostate: Novel treatment for age related disorders?
Authors: Rochel-Maia Sabrina S. , Taboga Sebastião R. , Warner Margaret , Gustafsson Jan-Åke 
Published: May 2013

Abstract
This study evaluated the effect of a selective estrogen receptor beta (ERβ) agonist in the prostate of the aging Mongolian gerbil. The gerbil is a rodent known for spontaneous development of prostatic lesions such as prostatic intraepithelial neoplasias (PIN), adenocarcinomas and micro invasive carcinomas as they become old. This representative feature makes the gerbil interesting for testing the role of novel targets to prevent or treat prostate cancer. ERβ is known to have anti-proliferative and pro-apoptotic effects in the prostate epithelium, and therefore is a potential target for treatment of prostatic disorders. ERβ agonist and vehicle pellets were implanted subcutaneously in 12-month-old male gerbils (n=5) and the ventral prostates were harvested after 3 and 7 consecutive days of treatment. The tissue was processed for light microscopy and stained for H&E for morphological analysis. Expression of the nuclear receptors AR, ERα and ERβ, as well as markers of proliferation and apoptosis were examined by immunohistochemistry. Anatomically, the prostates of gerbils treated with vehicle pellets were smaller and more compact than those treated for 3 days with the ERβ agonist. The change was due to increased volume of the ducts and return of the ductal epithelium to a single organized layer. Histologically, the slides stained with H&E showed a hyperplastic and inflamed epithelium with a dense stroma in the vehicle treated groups, as typical of senile gerbil prostates. However, the treatment with the ERβ agonist promoted a reorganization of the prostatic epithelium. Ducts became lined in single layer of cubic/columnar cells, with enlarged lumen, full of secretion. The hyperplastic phenotype had normalized. These effects were more prominent after 3 days than after 7 days and were confirmed by a decreased expression of the proliferation marker ki67. In addition, ERβ expression, which is usually very weak or undetectable in the prostate of 12-month-old gerbils, was fully recovered after 3 days of treatment while expression of ERα and AR remained the same, indicating the effects occurred via ERβ signaling exclusively. Upon 7 days of continuous exposure to the ERβ agonist, ERβ expression was down-regulated. Therefore, the results found so far are promising as they indicate the ERβ as a novel and effective target for the treatment of prostatic disorders. However, the route and regimen of drug delivery remains to be carefully worked out.
Citation Format: Sabrina S. Rochel-Maia, Sebastião R. Taboga, Margaret Warner, Jan-Åke Gustafsson. Effect of an ERβ agonist in the gerbil senile prostate: Novel treatment for age related disorders? [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 A53.
Abstract A9: Androgen-regulated miR-32 targets BTG2 and is overexpressed in castration-resistant prostate cancer
Authors: Jalava Sanni E. , Latonen Leena , Scaravilli Mauro , Waltering Kati K. , Seppälä Janne , Lähdesmäki Harri , Tammela Teuvo L.J. , Visakorpi Tapio 
Published: May 2013

Abstract
The androgen receptor (AR) signaling pathway is central to the emergence of castration-resistant prostate cancer (CRPC). We set out to identify androgen-regulated microRNAs (miRNAs) that may contribute to the development of CRPC. We found miR-32 to be an androgen regulated miRNA which is differentially expressed in CRPC compared to benign prostate hyperplasia (BPH) according to microarray analyses. qRT-PCR analyses confirmed that miR-32 expression increases in CRPC compared to BPH, and that in untreated prostate cancer (PC) miR-32 expression is higher in tumors of stage pT3 compared to pT2. Transfection of pre-miR-32 to prostate cancer cell line LNCaP provided a significant growth advantage to the cells, and miR-32 was further demonstrated to reduce apoptosis. To identify target genes for miR-32, an mRNA microarray analysis was performed with LNCaP cells transfected with pre-miR-32. In this assay, B cell translocation gene 2 (BTG2) was identified as a novel putative target for miR-32. BTG2 was reduced both at mRNA and protein level in the cells transfected with pre-miR-32, and BTG2 was confirmed to be a miR-32 target by 3′-UTR-luciferase assay. Furthermore, BTG2 was able to partially rescue the growth advantage of miR-32 in LNCaP cells. Immunostainings of prostate cancer patient material showed a statistically significant (p &lt; 0.0001) reduction of BTG2 protein in CRPCs compared to PC. The lack of BTG2 staining was also associated (p=0.0021) with a short progression-free time in patients who underwent prostatectomy and inversely correlated to miR-32 expression levels. In conclusion, we find that miR-32 is an androgen-regulated miRNA targeting BTG2 and overexpressed in CRPC. Thus, miR-32 is a potential marker for aggressive disease and is a putative drug target in PC.
Citation Format: Sanni E. Jalava, Leena Latonen, Mauro Scaravilli, Kati K. Waltering, Janne Seppälä, Harri Lähdesmäki, Teuvo L.J. Tammela, Tapio Visakorpi. Androgen-regulated miR-32 targets BTG2 and is overexpressed in castrationresistant 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 A9.
Abstract B13: Cycloartane-3,24,25-triol: A cancer chemopreventive cycloartane inhibits MRCKα kinase and demonstrates anti prostate cancer activity in vitro
Authors: Lowe Henry I.C. , Toyang Ngeh J. , Bryant Joseph 
Published: May 2013

Abstract
In our study of the Jamaican ball moss (Tillandsia recurvata L.) for its prostate cancer chemotherapeutic properties, we have identified a number of cycloartane-type compounds from the chloroform crude extract. Cycloart-23-ene-3,25-diol was isolated and characterized from the extract. Attempts to run this compound in our kinase and antiproliferative assays were unsuccessful because of solubility problems. A search of the literature led us to Cycloartane-3,24,25-triol, a close analog of Cycloart-23-ene-3,25-diol. Cycloart-23-ene-3,25-diol differs from Cycloartane-3,24,25-triol only in the presence of a third hydroxyl group in this compound while Cycloart-23-ene-3,25-diol has only two hydroxyl groups. We isolated Cycloartane-3,24,25-triol from its source plant (Chrysanthemum morifolium) and screened it against a 451 kinase panel for inhibitory properties as well as for anti- prostate cancer cell proliferation activity using DU145 and PC-3 cell lines. Cycloartane-3,24,25-triol inhibited MRCKα (Myotonic dystrophy kinase-related Cdc42–binding kinase) kinase at a Kd of 0.26μM and showed IC50 values of 1.56±0.18μM and 2.04±0.28μM against DU145 and PC-3 prostate cancer cell lines respectively. MRCK kinases are now known to contribute to the process of tumor progression and metastasis through the control of the cytoskeleton which regulates tumor cell motility and invasion. In prostate cancer, the MRCKα kinase indirectly contributes to tumor progression by activating other kinases including the Lim kinase 1 (LIMK 1) which is over-expressed in prostate cancer and known to contribute to tumor cell invasion and migration leading to metastasis to other organs. This is the first report on the anti-prostate cancer activity and kinase inhibitory activity of Cycloartane-3,24,25-triol. The combined kinase and in vitro antiproliferation activity of Cycloartane-3,24,25-triol makes it a good candidate for further studies to determine its in vivo efficacy against prostate cancer.
Citation Format: Henry I.C. Lowe, Ngeh J. Toyang, Joseph Bryant. Cycloartane-3,24,25-triol: A cancer chemopreventive cycloartane inhibits MRCKα kinase and demonstrates anti prostate cancer activity in vitro [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 B13.
Abstract B15: Development of a chimeric saporin peptide which targets human prostatecancer cells via monocyte delivery
Authors: Eskew Jeff , Troyer Deryl , Bossmann Stefan , Vielhauer George 
Published: May 2013

Abstract
Many attempts have been made to utilize plant and bacterial toxins to produce chimeric proteins that target and kill cancer cells; however, problems with specificity have slowed the progress of this potential therapy. We hypothesize that the specificity of these chimeric cytotoxic peptides can be improved by incorporating two layers of targeting. This will be accomplished by using the inherent tumor targeting properties of monocytes as well as engineering them to secrete a chimeric saporin peptide possessing a targeting element that is highly specific to human prostate cancer cells. Saporin is a small protein produced by soapwort that is a member of the ribosome inactivating protein (RIP) family. This family consists of some of the most potent toxins known to man, including ricin and abrin. RIPs act by gaining entry to the cell and then catalytically inactivating the ribosome. Ricin and abrin are very potent toxins because they contain two chains, a beta chain that gains entrance to the cell and an alpha chain that catalytically inactivates the ribosome. Saporin, unlike ricin or abrin, contains only the alpha chain; thus cell entry is prevented and making it, in theory, harmless unless it is attached to something that causes the cell to internalize it. In order to identify a highly specific and internalizable peptide that could be fused to a saporin molecule we screened a random 12-mer peptide bacteriophage library against the human prostate cancer cell line PC3. After several rounds of in-vitro and in-vivo biopanning we have isolated candidate peptides that appear specific and rapidly internalizable in PC3 cells. Using these peptides as targeting elements we propose to create a chimeric protein consisting of a signal peptide for secretion, a targeting peptide, and the cytotoxic saporin. This chimeric protein will be expressed in primary monocytes using a lentiviral system. Our preliminary data show that this fusion protein demonstrates profound cytotoxicity in PC3 cells within 72 hours. We have also developed an efficient orthotopic and metastatic human prostate cancer model in mice and have preliminary data showing monocyte recruitment to metastatic nodes. In conclusion, peptides that specifically target metastatic PC3 cells have been identified, in vivo, and have been linked to toxins that demonstrate potent cytotoxicity in vitro. Future studies will be to test the selective targeting of these toxic chimeric proteins, in vivo, utilizing primary and metastatic orthotopic tumor models of human prostate cancer in tumor efficacy studies.
Citation Format: Jeff Eskew, Deryl Troyer, Stefan Bossmann, George Vielhauer. Development of a chimeric saporin peptide which targets human prostatecancer cells via monocyte delivery [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 B15.