bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3198: Extract from Scutellaria baicalensis Georgi inhibits prostate cancer growth in bone
Authors: Li Chaoqian , Guo Hongwei , Lu Yi , Dai Jinlu , Keller Evan , Zhang Jian 
Published: May 2015

Abstract
Prostate cancer (PCa) frequently metastasizes to bone forming predominantly osteoblastic lesions with underlined osteolytic components. Because current therapies are generally ineffective in PCa skeletal metastases, patients seek alternative medicines such as herbal medicines, which have been used for many centuries in Asian countries. The purpose of this study was to identify Chinese herbal medicines that may be effective in PCa skeletal metastasis. We first screened 130 Chinese herbs (ethanol extracts) for anti-proliferation effects by non-radioactive cell proliferation assay in LNCaP and C4-2B PCa cells. We found five extracts with anti-proliferation activity including extract from Scutellaria baicalensis Georgi (Huang Qin, HQ), which had the strongest effect. We next evaluated HQ's ability to induce apoptosis of LNCaP and C4-2B cells. HQ, in a dose-dependent manner, induced apoptosis of both cell lines based on TUNEL assay. In addition, HQ induced apotosis-related gene caspase-3 and suppressed bcl-2 expressions in both cell lines. Therefore, we tested if HQ (1mg per mouse three times a week for 8 weeks intraperitoneally) could diminish establishment of skeletal metastases in mice. We injected C4-2B cells into tibia of SCID mice. The animals were randomized into two groups to receive either HQ or vehicle only (n=8/group). At 8 weeks post-tumor injection, mice were sacrificed and tumor establishment in the skeleton was determined using radiography, dual energy x-ray absorptiometry and histology. Radiographic and histological lesions were present in 7/8 vehicle-treated mice and in 6/8 HQ-treated mice. However, the radiographically- and histologically-determined areas of the tumors in the HQ-treated mice were approximately 47% that of the vehicle-treated animals. We conclude that HQ has efficacy for inducing PCa cells apoptosis in vitro and has the ability to diminish growth of PCa in murine bone. Supported by NSF key project 81130046, NSF projects 81171993 and 81272415.
Citation Format: Chaoqian Li, Hongwei Guo, Yi Lu, Jinlu Dai, Evan Keller, Jian Zhang. Extract from Scutellaria baicalensis Georgi inhibits prostate cancer growth in bone. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3198. doi:10.1158/1538-7445.AM2014-3198
Abstract 3216: Anti-proliferative properties of Euphorbia mauritanica medicinal plant against breast cancer
Authors: Choene Mpho S. , Motadi Lesetja R. 
Published: May 2015

Abstract
Over the decades, the increased interest in the use of natural resources in pharmaceutical and phytotherapeutic research has led to manufacture of drugs (including anti-cancer drugs) derived from natural sources With our increased understanding of the molecular mechanisms underlying cancer progression and cell death, it is therefore necessary to test if there are any natural products that can be used to act as antitumor agents. As breast cancer continues to be the leading cause of cancer in females, we aimed to exploit the use of South African traditional medicine, Euphorbia mauritanica as a tool for anti breast cancer therapy. Euphorbia mauritanica was tested for anti-proliferative properties against MCF-7 and Cama-1 breast cancer cell lines. The following solvents were used to extract active compounds from E. mauritanica: n-hexane, dichloromethane, chloroform, ethyl acetate, acetone, methanol and butanol. A real time cell analyzer (Xcelligence) was used to monitor cell growth over a period of 48 hours following treatment of cells with the extracts. Butanolic extracts showed the highest level of cytotoxicity on both MCF-7 and Cama-1 cell lines with IC50 of 15 and 30 µg/ml respectively. These were followed by hexanolic extracts with IC50 of 30 and 50 µg/ml and methanolic extracts with IC50 of 50 and 100 µg/ml. Flow cytometry using annexin V was further employed to determine if cell death was as a result of apoptosis and the data confirmed that this was most likely the case. On investigating whether the observed apoptosis was via p53 mediated pathway, western blot analysis of p53, bcl-2, caspase 9, caspase3, RBBP6 and mdm2 showed that treatment with the 3 extracts did not have a significant effect on any of these genes, suggesting that their mode of apoptosis induction maybe through an alternative apoptotic pathway.
Citation Format: Mpho S. Choene, Lesetja R. Motadi. Anti-proliferative properties of Euphorbia mauritanica medicinal plant against breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3216. doi:10.1158/1538-7445.AM2014-3216
Abstract 3218: Zyflamend, a multi-herbal product, selectively inhibits the growth of triple negative breast cancer cells in vitro
Authors: Gutierrez-Barrera Angelica M. , Arun Banu K. , Yang Peiying , Cartwright Carrie 
Published: May 2015

Abstract
Triple negative breast cancer (TNBC), a subpopulation of breast cancer that has a high mortality rate, recently has been shown to be quite diverse with approximately 7 different molecular subtypes. As a result, treatment with an agent that can potentially target multiple pathways might be an effective approach. Zyflamend (Zy), a unique herbal preparation consisting of 10 concentrated herbal extracts, has been shown to suppress the proliferation of various cancer cells including prostate, melanoma, and bladder cancers. However, its role in TNBC has not been investigated. To examine its anticancer activity in TNBC, we utilized a crystal violet staining assay to determine the proliferation of cells, FACS analysis for cell cycle and apoptosis and gene/protein expression analysis to delineate the plausible mechanism of action. Among a number of breast cancer cell lines including MCF-7, SUM149, MDMB231, BT549 and HCC1937, Zy exerted stronger inhibitory effect in all TNBC cells with IC50 values ranging between 400-800μg/ml (0.5-1 μl/ml) whereas MCF-7, an estrogen/progesterone receptor positive cell line, required 1000μg/ml (1.5μl/ml). Similarly, the morphologies of SUM149, MDAMB231, and BT549 cell lines were notably disrupted by Zy treatment (400μg/ml) when these cells were cultured using three dimensional techniques. FACS analysis showed that there was a dramatic shift to subG1 phase, suggesting cells might undergo apoptosis. Reverse Phase Proteomic Array indicated that proteins affecting the cell cycle progression, cell junction regulation, and cell signaling were altered in BT549 and HCC1937 by 24 hr Zy treatment (800μg/ml).. When compared to the vehicle control, gene expression analysis showed that several inflammatory genes were downregulated by at least 50% and these included 5- and 12-lipooxygenase, leukotriene receptors, TNF receptor, and NF-κB in HCC1937 (800μg/ml), MDAMB231(800μg/ml) and SUM149 (400μg/ml) cells. Taken together, our preliminary data suggests that Zy inhibits TNBC proliferation by inhibiting inflammation, regulating cell cycle, and inducing cell death. Further studies are ongoing to evaluate these effects in in vivo triple negative breast cancer models.
Citation Format: Angelica M. Gutierrez-Barrera, Banu K. Arun, Peiying Yang, Carrie Cartwright. Zyflamend, a multi-herbal product, selectively inhibits the growth of triple negative breast cancer cells in vitro. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3218. doi:10.1158/1538-7445.AM2014-3218
Abstract 3225: LEDGF IBD domain represents therapeutic target for MLL leukemia and HIV
Authors: Cierpicki Tomasz , Murai Marcelo J. , Pollock Jonathan , Purohit Trupta , He Shihan , Yokom Adam , Hess Jay L. , Muntean Andrew G. , Grembecka Jolanta 
Published: May 2015

Abstract
Lens epithelium-derived growth factor (LEDGF) is a chromatin associated protein implicated in cell survival, cancer, autoimmune diseases and HIV pathogenesis. LEDGF is also involved in recurring chromosomal translocations with nucleoporin NUP98 in acute leukemia, and the LEDGF/p75 isoform is consistently upregulated in a subset of acute myeloid leukemias (AML) resistant to chemotherapy. Moreover, it has been established that LEDGF is an essential co-factor required for oncogenic activity of MLL fusion proteins in leukemia. LEDGF interacts simultaneously with MLL and menin and is necessary for up-regulation of HOXA9 gene and for leukemogenic transformation by MLL fusion proteins in vivo. Therefore, LEDGF represent a valuable molecular target for therapeutic intervention as a novel targeted therapy for MLL leukemia patients. Furthermore, targeting LEDGF may represent an attractive alternative to inhibition of the menin-MLL interaction as it will allow preserving the function of menin, a known tumor suppressor in endocrine tissues.
We determined the solution structure of MLL fragment bound to LEDGF IBD domain and identified a novel hydrophobic motif within MLL, which we called IBM2, that is required for high affinity interaction with LEDGF. Point mutations within IBM2 abolished leukemogenic activity of MLL-AF9, indicating that IBM2 represents a critical site for formation of a high affinity menin-MLL-LEDGF complex. Furthermore, we found that short peptide corresponding to IBM2 binds to IBD domain and disrupts the interaction of LEDGF with the menin-MLL complex, providing a proof of concept that the novel interface on IBD domain we identified represents a druggable site for small molecule intervention.
LEDGF plays also an essential role in pathogenesis of HIV-1 virus and is required for integration of viral cDNA. Targeting HIV integrase to disrupt the interaction with LEDGF has been recognized as an attractive approach to develop new anti-viral agents. Importantly, the new MLL binding site on IBD domain we found overlaps with the binding site of HIV integrase. Therefore, targeting the IBM2 site on IBD may represent a novel approach to target the LEDGF-integrase interaction. In summary, our findings pave the way towards development of new therapeutic agents with dual applications for both MLL leukemias and HIV.
Citation Format: Tomasz Cierpicki, Marcelo J. Murai, Jonathan Pollock, Trupta Purohit, Shihan He, Adam Yokom, Jay L. Hess, Andrew G. Muntean, Jolanta Grembecka. LEDGF IBD domain represents therapeutic target for MLL leukemia and HIV. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3225. doi:10.1158/1538-7445.AM2014-3225
Abstract 3226: GALNT6 stabilizes GRP78 protein by O-type glycosylation
Authors: Park Jae-Hyun , Chung Suyoun , Lin Jiaying , Ueda Koji , Katagiri Toyomasa , Nakamura Yusuke 
Published: May 2015

Abstract
Aberrant O-type glycosylation is predominantly detected in breast cancer and plays diverse roles in cancer cell proliferation, metastasis, and drug resistance. GALNT (polypeptide N-acetylgalactosaminyl transferase) family initiates the O-type glycosylation and its high activity accounts for aberrant O-type glycosylation in breast cancer. We previously suggested that GALNT6 is a promising molecular target in breast cancer and involved in O-type glycosylation of Mucin 1 and fibronectin. To further investigate the molecular function of GALNT6, we performed pull down assay using VVA (Vicia Villosa agglutinin) lectin and identified several O-glycosylated proteins specifically in GALNT6-positive stable cells. After in vitro and in vivo O-glycosylation assays, we confirmed GRP78 (glucose related protein 78) as a physiological substrate of GALNT6 and identified 5 O-glycosylation sites in GRP78 by mass spectrometry. GRP78 is a molecular chaperone that facilitates proper protein folding under cellular stress. Interestingly, accumulating evidences have indicated that GRP78 plays anti-apoptotic roles in cancer cells against chemotherapy. Exogenous induction of GALNT6 increased the amount of GRP78 protein without any changes in its transcriptional level. Concordantly, knockdown of GALNT6 significantly reduced the GRP78 protein. Collectively, our findings imply that GALNT6 stabilizes GRP78 via O-glycosylation and GALNT6 inhibitor will be able to sensitize breast cancer cells to chemotherapy.
Citation Format: Jae-Hyun Park, Suyoun Chung, Jiaying Lin, Koji Ueda, Toyomasa Katagiri, Yusuke Nakamura. GALNT6 stabilizes GRP78 protein by O-type glycosylation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3226. doi:10.1158/1538-7445.AM2014-3226
Abstract 3244: Supplementation with selenium-enriched yeast but not selenomethionine reduces oxidative stress in healthy men in a randomized clinical trial
Authors: Kaag Matt G. , Richie John P. , Das Arun , Calcagnotto Ana , Sinha Raghu , Neidig Wanda , Liao Jiangang , Lengreich Eugene J. , Berg Arthur , Hartman Terryl J. , Ciccarella Amy , Baker Aaron , Boyiri Telih , Goodin Susan , DiPaola Robert S. , El-Bayoumy Karam 
Published: May 2015

Abstract
Epidemiological and laboratory studies indicate that dietary selenium is protective against prostate cancer. Results from clinical trials suggest that selenium-enriched yeast (SY) but not selenomethionine (SeMet) may be effective at reducing prostate cancer risk. Our objectives were to directly compare for the first time the effects of SeMet and SY on prostate cancer relevant biomarkers in men. We performed a randomized double blind, placebo-controlled trial of SY (200 or 285 μg/day) and SeMet (200 μg/day) administered for 9 months in 69 healthy adult males. Biomarkers including blood selenium, glucose, PSA and glutathione (GSH) and urine 8-hydroxy-2’-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α) were measured at baseline and various times thereafter. Compliance was high in all groups (&gt;95%). Plasma selenium levels were increased 93%, 54%, and 86% after 9 months in the SeMet and low and high dose SY groups, respectively, and returned to baseline levels after a 3 month washout (P&lt;0.05). Urinary biomarkers of oxidative stress, 8-OHdG and 8-iso-PGF2α, were decreased 34% and 28%, respectively, after 9 months in the high dose SY group (P&lt;0.05). Decreases in oxidative stress biomarkers were greatest in individuals with low baseline plasma levels of selenium (&lt;127 ng/ml). No changes in serum PSA or blood glucose and GSH were observed. We showed for the first time reductions in biomarkers of oxidative stress following supplementation with SY but not SeMet in healthy men. These findings suggest that selenium-containing compounds other than SeMet may be responsible for the decrease in oxidative stress and possibly cancer risk. This work was supported a National Cancer Institute grant (R01CA127729).
Citation Format: Matt G. Kaag, John P. Richie, Arun Das, Ana Calcagnotto, Raghu Sinha, Wanda Neidig, Jiangang Liao, Eugene J. Lengreich, Arthur Berg, Terryl J. Hartman, Amy Ciccarella, Aaron Baker, Telih Boyiri, Susan Goodin, Robert S. DiPaola, Karam El-Bayoumy. Supplementation with selenium-enriched yeast but not selenomethionine reduces oxidative stress in healthy men in a randomized clinical trial. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3244. doi:10.1158/1538-7445.AM2014-3244
Abstract 329: Rottlerin induced autophagy by targeting multiple sites that leads to the apoptosis in cancer stem cells
Authors: Kumar Dhruv 
Published: May 2015

Abstract
Autophagy plays an important role in maintaining cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via degradation of aggregated proteins and damaged organelles. Autophagy is associated with the several catabolic and pathological processes, including cancer. Cancer is a multifaceted disorder involving the perturbation of several different pathways that regulate cell proliferation, cell differentiation, and cell survival. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to apoptosis in cancer stem cells. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, rottlerin, from a medicinal plant (Mallotus philippinensis) that induces autophagy in various types of cancer stem cells through the formation of autophagosomes as measured by electron microscopy and GFP-LC3 puncta formation. By computational virtual docking analysis, rottlerin was shown to interact directly with the protein kinase-C delta, beclin-1, and autophagy related proteins. By biochemical assays, rottlerin was shown to increase autophagy induction through the activation of the kinase-AMP-activated protein kinase-mammalian target of rapamycin pathway. In addition, rottlerin treatment causes the induction of apoptosis, which was associated with the suppression of phosphorylated Akt and mTOR, upregulation of phosphorylated kinase-AMP, downregulation of Bcl-2, Bcl-XL, XIAP, and cIAP-1. Rottlerin also proved to be a potent autophagy inducer in cancer stem cells, by knocking down beclin-1, protein kinase-C delta, or Agt7. These results provide a detailed understanding of the mechanism of action of rottlerin, as a novel autophagic inducer by targeting multiple sites to induce autophagy, which leads to the apoptosis in cancer stem cells. Rottlerin has the potential of being developed into an anti-cancer agent by targeting cancer stem cells.
Citation Format: Dhruv Kumar. Rottlerin induced autophagy by targeting multiple sites that leads to the apoptosis in cancer stem cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 329. doi:10.1158/1538-7445.AM2014-329
Abstract 3302: CD146, a suppressor of breast cancer, is a novel target of CD44-signaling
Authors: Abdraboh Mohamed E. , Al-Riyami Hamad , Al-Farsi Yahya , Ouhtit Allal , Hollenbach Andrew D. , Gupta Ishita , Shanmuganathan Somya , Raj Madhwa H. 
Published: May 2015

Abstract
More than 80% of cancer related deaths are caused by cancer cell metastasis, a crucial step in the onset of tumor development. Among the molecules involved in promoting cancer metastasis is the cell adhesion molecule CD44, whose role in promoting cancer cell motility and metastasis is well known. Despite this knowledge, the molecular mechanism through which CD44 promotes tumor development and cell metastasis is still unclear. CD146 (MUC 18) is another member of the cell adhesion molecule family, first identified in highly metastatic melanomas. The absence of CD146 in normal melanocytes and its high expression in melanomas suggests its tumor promoting actions. Despite the association between CD146 expression and development of melanoma, the expression patterns and the role of CD146 in normal and metastatic breast tissues are still controversial. In this paper we provided evidence clarifying some of these discrepancies by presenting CD146 as a negative downstream target for CD44. Finally, this study demonstrates a new role of CD44 in regulating neovascularization and in promoting cancer cell transmigration of blood vessels via regulation of its downstream target CD146.
Citation Format: Mohamed E. Abdraboh, Hamad Al-Riyami, Yahya Al-Farsi, Allal Ouhtit, Andrew D. Hollenbach, Ishita Gupta, Somya Shanmuganathan, Madhwa Hg Raj. CD146, a suppressor of breast cancer, is a novel target of CD44-signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3302. doi:10.1158/1538-7445.AM2014-3302
Abstract 3308: A-kinase anchoring protein 2 is required for calcitonin receptor-stimulated invasion of prostate cancer cells
Authors: Aljameeli Ahmed , Thakkar Arvind , Thomas Shibu , Shah Girish V. 
Published: May 2015

Abstract
Expression of neuropeptide calcitonin (CT) and its receptor (CTR) is frequently elevated in prostate cancers (PCs) and activation of CT-CTR axis in non-invasive PC cells induces an invasive phenotype. CTR-stimulated invasion of prostate cancer cells, which is abolished by specific, cell-permeable inhibitors of protein kinase A. Since PKA is ubiquitously distributed in cells, present study examined the mechanism(s) by which CTR-stimulated PKA activity is regulated in time and space.
CT reduced cell adhesion but increased invasion of prostate cancer cells, both actions were abolished by AKAP St-Ht31 inhibitor peptide suggesting the involvement of an AKAP in CT action. Next, we identified the AKAP associated with CT action by subtraction of AKAP candidates using siRNAs. Knock-down of AKAP2, but not other AKAPs, abolished CT stimulated invasion. AKAP2 was localized to the plasma membrane. Stable knock-down of AKAP2 in PC3-CTR cells remarkably decreased cell proliferation, invasion, clonogenicity and their ability to form orthotopic tumors and distant metastases in nude mice. Reexpression of AKAP2-wt restored these characteristics. Primary prostate cancer specimens displayed remarkable up-regulation of CTR/AKAP2 expression as compared to benign prostates. Metastatic cancers displayed significantly higher CTR/AKAP2 expression than localized cancers.
These results for the first time demonstrate that AKAP2 is expressed in human prostates, its expression is elevated in metastatic prostate cancer, and the knock-down of its expression remarkably decreased tumorigenicity and metastatic ability of prostate cancer cells. AKAP2 may serve as a critical component of CTR-mediated oncogenic actions.
Citation Format: Ahmed Aljameeli, Arvind Thakkar, Shibu Thomas, Girish V. Shah. A-kinase anchoring protein 2 is required for calcitonin receptor-stimulated invasion of prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3308. doi:10.1158/1538-7445.AM2014-3308