bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2237: Synthesis and characterization of novel, membrane permeable estradiol fluorophores that maintain estrogenic activity.
Authors: Stailey Jason E. , Hapuarachchige Sudath , Ramesh Chinnasamy , Shrestha Sanjay , Wimbley Angelique M. , Shuster Charles B. , Arterburn Jeffrey B. , Houston Kevin D. 
Published: August 2014

Abstract
The ability to label biomolecules with fluorescent tags has become essential in basic cancer research and offers great promise for improvements in clinical diagnostics. The structure and physicochemical properties of the fluorescent tag have the potential of altering binding and activity characteristics of the conjugates, therefore it is desirable to use small, neutral, membrane permeable and biocompatible fluorescent tags with favorable photophysical properties, and versatile coupling chemistries. . Estradiol (E2) is a well-characterized ovarian steroid hormone with known measureable biological endpoints at the cellular, transcriptional, and signal transduction levels. We synthesized a new class of fluorescent estrogen derivatives from 17-alpha-ethynylestradiol conjugated to triazaborolopyridinium (HPY) dyes. The estrogenic activity of the covalently linked E2-HPY fluorophores were characterized using the MCF-7 breast cancer cell line, an E2-dependent cell line that is often used as a model system to study E2-induced cell responses. The MCF-7 cells were treated with a series of E2-HPY derivatives (10nM), E2 (10nM) or vehicle control. The time points for treatment was as short as 15 minutes for effect on signal transduction to 5 days for cell proliferation endpoints. After treatment for specified time points, E2-induced proliferation was determined by growth curve analysis (1-5 days), E2-mediated progesterone receptor (PR) transcription was determined by real-time PCR (24 hours), and E2-dependent accumulation of pERK was measured by immunoblot analysis (15min). Our results indicate that the bioactivity of E2-HPY was not significantly different from unconjugated E2 for the three endpoints tested. The accumulation of E2-HPY in cells was demonstrated by flow cytometry and fluorescence microscopy. These data indicate that E2-HPY is taken up by cells and is easily detectable. Additionally, transcriptome analysis was performed to identify potential differences in general transcriptional activation between E2 and E2-HPY. These data suggest the exciting possibility that HPY fluorophores can be covalently linked to cancer-related biomolecules to enhance basic research and for potential use as a cancer diagnostic tool in the clinical.
Citation Format: Jason E. Stailey, Sudath Hapuarachchige, Chinnasamy Ramesh, Sanjay Shrestha, Angelique M. Wimbley, Charles B. Shuster, Jeffrey B. Arterburn, Kevin D. Houston. Synthesis and characterization of novel, membrane permeable estradiol fluorophores that maintain estrogenic activity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2237. doi:10.1158/1538-7445.AM2013-2237
Abstract 2240: Structural variant of osteoprotegerin lacking TRAIL binding for therapeutic bone remodeling in osteolytic malignancies.
Authors: Higgs Jerome T. 
Published: August 2014

Abstract
Current treatments for osteolytic cancer pathology include a combination of radiation and chemotherapy, but toxic side effects are still of major concern. Studies have shown that osteoclast activity is increased in patients with osteolytic cancers such as multiple myeloma, breast and prostate cancer through increased expression of Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) leading to RANKL/RANK signaling, resulting in osteoclast activation and ultimately bone resorption. Moreover, Osteoprotegerin (OPG), a decoy receptor for RANKL, is disproportionately expressed in these patients who present with bone lesions. Thus, the use of OPG as a therapeutic molecule would greatly decrease osteolytic damage and reduce morbidity. However, despite the potential of OPG in inhibiting the activation of osteoclast, OPG also binds to tumor necrosis factor related apoptosis-inducing ligand (TRAIL) making tumor cells resistant to apoptosis. TRAIL binds to the Death Receptor 4 and 5 (DR4, DR5) and initiate cell death of transformed cells such as MM. The goals of this study was to designed and develop a therapeutic approach to the treatment of osteolytic bone damage by use of genetically altered OPG retaining RANKL binding but abolished in TRAIL binding. Towards uncoupling the events of TRAIL binding of OPG and to improve its utility for bone remodeling without inducing tumor resistance to apoptosis, we created a genetic variant of OPG through structural homology model based on interactive domain identification and by superimposing structural models of TRAIL, OPG and DR5 to identify regions of OPG for rational design. The mutant OPG (mut-OPG) was purified and extensively characterized for its ability for decreasing osteoclast damage without affecting tumor apoptosis pathway both in vivo and in vitro indicating its potential for therapy targeting bone lesions in osteolytic malignancies.
Citation Format: Jerome T. Higgs. Structural variant of osteoprotegerin lacking TRAIL binding for therapeutic bone remodeling in osteolytic malignancies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2240. doi:10.1158/1538-7445.AM2013-2240
Abstract 2241: Possible involvement of glycolipids in anticancer drug resistance of human ovarian serous carcinoma-derived cells.
Authors: Tanaka Kyoko , Aoki Daisuke , Isonishi Seiji , Mikami Mikio , Kiguchi Kazushige , Iwamori Masao 
Published: August 2014

Abstract
To further characterize the molecular basis on anticancer drug-resistance of human ovarian carcinoma, we compared glycolipid and transporter gene expressions in ovarian serous carcinoma-derived KF28 and 2008 cells with those in their paclitaxel- and cisplatin-resistant cells. Lipid compositions were determined by TLC and TLC-immunostaining and gene expressions of transporter proteins and glycosyltransferases were by RT-PCR. Although the amounts of major lipids, i.e. cholesterol, ceramides and phospholipids, in the resistant cells were same with those in the sensitive cells, Gb3Cer was commonly increased in all resistant cells, irrespective of whether the resistance was to paclitaxel or cisplatin. Also, expressions of the MDR1 gene and gangliosides, GM3 for KF28, and GM1 and GD1a for 2008 cells, were enhanced in paclitaxel-resistant cells, but gangliosides were absent in cisplatin-resistant cells. In accord with the decreased amounts of gangliosides in cisplatin-resistant cells, the gene expression and specific activity of GM3 synthase were greatly decreased in cisplatin-resistant cells. One can suggest that increased amount of Gb3Cer in cisplatin-resistant cells is brought about by the metabolic shifts of LacCer-modifying pathway from GM3- to Gb3Cer-synthases. Furthermore, paclitaxel- and cisplatin-resistant cells were converted to forms more sensitive to the respective anticancer drugs on cultivation with D-PDMP, an inhibitor of GlcCer synthase, and GM3, respectively, prior to the addition of anticancer drugs. Thus, coexpression of the MDR1 gene and glycolipids including gangliosides was thought to be necessary for survival of cells in media containing paclitaxel through regulation of transporter proteins with glycolipids in membrane rafts. Also, the decreased amounts of gangliosides might contribute to the cisplatin resistance, probably by the reduced incorporation of cisplatin.
Citation Format: Kyoko Tanaka, Daisuke Aoki, Seiji Isonishi, Mikio Mikami, Kazushige Kiguchi, Masao Iwamori. Possible involvement of glycolipids in anticancer drug resistance of human ovarian serous carcinoma-derived cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2241. doi:10.1158/1538-7445.AM2013-2241
Abstract 2243A: Discovery of potent hedgehog pathway inhibitors as potential anticancer agents.
Authors: Cai Sui Xiong , Xie Kai , Li Sicun , Wu Lizhen , Liu Lijun , Yin Feng , Gu Chengyun , Wang Xiaozhu , Kang Sishun , Chen Shengzhi , Meng Zheng , Zhang Yan , Wang Guoxiang , Fei Hongqiang , Wang Dongmei , Tian Ye Edward 
Published: August 2014

Abstract
The hedgehog (Hh) pathway is critically important for embryonic development, and interference with the Hh pathway could result in severe birth defect. The Hh pathway is known to be highly activated in certain cancers such as basal cell carcinoma (BCC) and medulloblastoma. The approval of hedgehog pathway inhibitor Erivedge (vismodegib, GDC-0445) for the treatment of adults BCC by FDA in early 2012 validated Hh pathway as an anticancer target.In this presentation, we report the discovery of novel hedgehog pathway inhibitors and the identification of lead compounds that are 10-100 fold more potent in multiple in vitro assays than GDC-0449. Several of these potent compounds have been found to have good oral bioavailability and brain penetration. The in vivo efficacy studies of selected compounds are in progress.
Citation Format: Sui Xiong Cai, Kai Xie, Sicun Li, Lizhen Wu, Lijun Liu, Feng Yin, Chengyun Gu, Xiaozhu Wang, Sishun Kang, Shengzhi Chen, Zheng Meng, Yan Zhang, Guoxiang Wang, Hongqiang Fei, Dongmei Wang, Ye Edward Tian. Discovery of potent hedgehog pathway inhibitors as potential anticancer agents. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2243A. doi:10.1158/1538-7445.AM2013-2243A
Abstract 2246: Steam distilled ginger extract inhibits endometrial cancer cell proliferation by activating P53 and causing apoptosis.
Authors: Liu Yang , Whelan Rebecca J. , Pattnaik Bikash R. , Ludwig Kai David , Landeros Rosalina V. , Subudhi Enkateswar , Rowland Helen , Claussen Nicholas , Zucker Noah , Uppal Shitanshu , Kushner David M. , Felder Mildred , Patankar Manish S. , Kapur Arvinder K. 
Published: August 2014

Abstract
Phenolic compounds present in dry ginger powder or solvent extracts of ginger roots induce cell cycle arrest and apoptosis in skin, breast, prostate, colon, and ovarian cancer cells. Another class of bioactive compounds, the terpenes, can be isolated by steam distillation of the ginger rhizomes. In this study, we examine the anti-cancer properties of Steam Distilled Ginger Extracts (SDGE) on endometrial cancer cells.
SDGE at an IC-50 of 1.5 micrograms/ml inhibited the proliferation of two endometrial cancer cell lines, ECC-1 and Ishikawa. Decreased proliferation of Ishikawa and ECC-1 cells was a direct result of SDGE-induced-apoptosis as demonstrated by Annexin V FITC staining and increased expression of cleaved caspase 3. GC-MS analysis allowed us to identify 22 distinct terpenes in SDGE. Gingerols and other non-terpene phenolic compounds were not present in SDGE. Neral and Geranial constituted 25-35% of the total SDGE terpenes and were found to inhibit endometrial cancer cell proliferation. On the other hand, camphene and α-pinene, which together constitute 10% of SDGE, showed no effect on the proliferation of ECC-1 and Ishikawa cells. SDGE at concentrations as low as 25 nanograms/ml caused a rapid increase in intracellular calcium levels and an approximate decrease of 20% in the mitochondrial membrane potential. Ser-15 of p53 was phosphorylated after a 15 minute treatment of the cancer cells with SDGE (250 nanograms/ml). This activation of p53 was associated with a 90% decrease in Bcl2, whereas no effect was observed on Bax. Pifithrin-α, an inhibitor of p53, attenuated the anti-cancer effects of SDGE that result from apoptosis. In addition, SDGE (1.5 microgram/ml) was unable to induce apoptosis in the p53-negative ovarian cancer cell line, SKOV3. Our data therefore indicates that specific terpenes present in SDGE are highly efficient in controlling the growth of p53-expressing cancer cells. We therefore propose that SDGE and its constituent bioactive terpenes should be further investigated as anti-cancer agents.
Citation Format: Yang Liu, Rebecca J. Whelan, Bikash R. Pattnaik, Kai David Ludwig, Rosalina V. Landeros, Enkateswar Subudhi, Helen Rowland, Nicholas Claussen, Noah Zucker, Shitanshu Uppal, David M. Kushner, Mildred Felder, Manish S. Patankar, Arvinder K. Kapur. Steam distilled ginger extract inhibits endometrial cancer cell proliferation by activating P53 and causing apoptosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2246. doi:10.1158/1538-7445.AM2013-2246
Abstract 2247: Ganoderma lucidum (Reishi) downregulates key proteins overexpressed in IBC and chemosensitizes EGFR-overexpressing cells to erlotinib.
Authors: Suarez-Arroyo Ivette , Rosario-Acevedo Raysa , Aguilar-Pérez Alexandra , Cubano Luis A. , Martínez-Montemayor Michelle M. 
Published: August 2014

Abstract
Inflammatory Breast Cancer (IBC) is a unique and aggressive cancer where tumor spheroids invade the dermal lymphatics causing the inflammatory phenotype. IBC cell lines and human tissues overexpress plasma membrane proteins such as E-cadherin and Epidermal Growth Factor Receptor (EGFR), which are associated with maintaining tumor spheroid integrity, increased IBC tumor growth rate, invasion and metastasis. Since IBC tumor cell emboli are more efficient at forming metastases and are more resistant to chemo and radiotherapy than single cells, it seems feasible to prevent IBC with a compound that has the ability to disintegrate the cell spheroids. Our published data shows that the medicinal mushroom, Ganoderma lucidum (Reishi), inhibits IBC progression via disintegration of tumor spheroids. Thus, we aimed to investigate Reishi's in vitro and in vivo therapeutic potential in IBC, focusing on the regulation of E-cadherin and EGFR and its contribution to the IBC cellular response when treated with the EGFR Tyrosine Kinase Inhibitor (TKI), erlotinib (commercially known as Tarceva®). Herein, we show that Reishi downregulates E-cadherin and EGFR abundance in vitro, significantly reduces tumor growth by 58%, and downregulates in vivo EGFR, and E-cadherin protein expression. Moreover, a synergistic effect is observed when erlotinib and Reishi are used simultaneously after 72 hours of treatment. Since Reishi downregulates the expression of E-cadherin and EGFR, our subsequent investigations will focus on the identification of PM proteins using stable isotope labeling with amino acids in cell culture (SILAC). Our results provide evidence that Reishi downregulates key proteins overexpressed in IBC, and chemosensitizes IBC cells to erlotinib therapy, highlighting its anti-IBC-therapeutic potential. This project was sponsored by Title V PPOHA US Dept of Education #P031M105050 to UCC, NIH/RCMI #2G12RR003035 to UCC, NIH/INBRE #5P20RR016470 to UPR/UCC, NIH/NCRR #U54RR026139 to UPR/UCC, and a research donation from the Commonwealth of Puerto Rico to UCC-Centro Universitario de Medicina Integral y Complementaria (CUMIC) / MMM.
Citation Format: Ivette Suarez-Arroyo, Raysa Rosario-Acevedo, Alexandra Aguilar-Pérez, Luis A. Cubano, Michelle M. Martínez-Montemayor. Ganoderma lucidum (Reishi) downregulates key proteins overexpressed in IBC and chemosensitizes EGFR-overexpressing cells to erlotinib. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2247. doi:10.1158/1538-7445.AM2013-2247
Abstract 2252: Mechanism of thymoquinone-induced cell death in glioblastoma multiforme.
Authors: Racoma Ira O. , Snapka Robert M. , Wani Altaf A. 
Published: August 2014

Abstract
Glioblastoma (GBM) is the most aggressive and common type of brain tumor in humans. Surgical resection followed by radiation and chemotherapy is the current standard treatment; however, due to the upregulation of several survival pathways, tumor recurrence is quite common with a median survival of 12 to 15 months. Therefore, there is an urgent need for more effective therapeutic strategies for the treatment of glioblastoma. Naturally occurring phytochemicals have steadily received much scientific attention, owing to the fact that many of these compounds have potent action against tumors. Thymoquinone (TQ) is the bioactive compound of the volatile oil extracted from the black seed, Nigella sativa. TQ has shown anti-oxidant, anti-inflammatory and anti-neoplastic actions with a selective cytotoxicity for human cancer cells compared to several normal cells. Here, we show that TQ can dose-dependently inhibit colony formation in three distinct glioblastoma cell lines, with the highly tumorigenic Gli36ΔEGFR displaying the greatest sensitivity to the anti-proliferative effects of TQ. Moreover, normal human astrocytes are far less sensitive to TQ-induced cell kill. The absence of both DNA fragmentation and PARP cleavage in U87 and Gli36ΔEGFR cells suggests that TQ does not activate apoptosis. We show that TQ does not change the levels of Beclin-1 expression, but does cause accumulation of LC3-II and p62 protein levels. This suggests that TQ blocks the late stages of autophagy. TQ-induced cell death can be partially rescued by co-treatment with a lysosomal cathepsin hydrolase inhibitor III. We also show that TQ induces persistent γ-H2AX activation and causes G2/M cell cycle arrest in GBM cells to a degree that correlates with the cells’ relative clonogenic sensitivity. Moreover, co-treatment with TQ and N-acetyl cysteine, a simple thiol nucleophile and antioxidant, prevented cell death, DNA double strand breaks, and cell cycle arrest.
Citation Format: Ira O. Racoma, Robert M. Snapka, Altaf A. Wani. Mechanism of thymoquinone-induced cell death in glioblastoma multiforme. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2252. doi:10.1158/1538-7445.AM2013-2252
Abstract 2254: A novel chemopreventive mechanism for a traditional medicine: East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes.
Authors: Levenson Corey , Olson Erik R. , Alberts David S. , Bowden G. Tim 
Published: August 2014

Abstract
α-Santalol, one of the primary components of the East Indian sandalwood oil (EISO), has been investigated for its potential use as a chemopreventive agent in skin cancer. Although there is some evidence that α-santalol could be an effective chemopreventive agent, to date, purified EISO has not been investigated. EISO is widely used for its health benefits in cultures around the world. In the current study, we show for the first time that EISO-treatment of cultured keratinocytes inhibits cell cycle progression and UV-induced AP-1 activity, two major cellular effects known to drive skin carcinogenesis. Unlike many chemopreventive agents, inhibition of signaling upstream of AP-1 was not a primary means of EISO-mediated AP-1 inhibition, as no effect of EISO was observed on UV-induced Akt, ERK, and p38 MAPK activity. EISO induced cell death at low concentrations, although caspase and PARP cleavage were not observed indicating that death was not due to apoptosis. Interestingly, plasma membrane integrity was severely compromised in EISO-treated cells and LC3 cleavage suggests the induction of autophagy. These effects were more pronounced in EISO-treated cells that were stimulated to proliferate than in quiescent cells. Together, these effects suggest that EISO has chemopreventive properties and may be useful as in preventing skin carcinogenesis.
Citation Format: Corey Levenson, Erik R. Olson, David S. Alberts, G. Tim Bowden. A novel chemopreventive mechanism for a traditional medicine: East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2254. doi:10.1158/1538-7445.AM2013-2254
Abstract 2267: Natural product-inspired drug discovery: Chemistry and biology of oridonin analogs with unique scaffolds and enhanced anticancer profiles .
Authors: Ding Chunyong , Zhang Yusong , Chen Haijun , Yang Zhengduo , Chu Lili , Wild Christopher , White Mark A. , Shen Qiang , Zhou Jia 
Published: August 2014

Abstract
ABSTRACT: Oridonin, a complex ent-kaurane diterpenoid isolated from Chinese traditional herb Rabdosia rubescens (Chinese name "Donglingcao"), has demonstrated great potential in the treatment of various human cancers due to its unique, safe and remarkable anticancer pharmacological profile. Nevertheless, the clinical development of oridonin for cancer therapy has been hampered by its relatively moderate potency, limited aqueous solubility and bioavailability. Up to now, the oridonin-based structural modifications and relevant structure-activity relationship remain sparse partially because of the challenging synthesis and structural complexity. To develop novel oridonin derivatives with enhanced anticancer potency and solubility, a sizable compound library of oridonin analogs with unique scaffolds is being established in our laboratories through diversity-orientated synthesis. Our successful synthetic strategies include heterocycle-fused ring A construction, and ring A-based α,β-unsaturated enone formation, as well as other stereoselective and regioselective approaches. A number of novel nitrogen-enriched heterocyclic oridonin derivatives and dienone analogs such as CYD0554, CYD0618, CYD0628, CYD0630, CYD0686, and CYD0692 have been identified with potent anti-proliferation effects against breast, pancreatic, and prostate cancer cells with low micromolar to nanomolar IC50 values. Moreover, some of them also exhibit significantly improved aqueous solubility and enhanced anticancer profiles for the treatment of estrogen receptor (ER)-negative including triple-negative breast cancer in comparison with oridonin. Our success in the chemical design, synthesis and biological characterization of these new molecules opens new avenues to develop promising natural product-like drug candidates for cancer therapy.
Key Words: Natural products, Oridonin analogs, Diversity-orientated synthesis, Anticancer agents, Drug discovery
Citation Format: Chunyong Ding, Yusong Zhang, Haijun Chen, Zhengduo Yang, Lili Chu, Christopher Wild, Mark A. White, Qiang Shen, Jia Zhou. Natural product-inspired drug discovery: Chemistry and biology of oridonin analogs with unique scaffolds and enhanced anticancer profiles . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2267. doi:10.1158/1538-7445.AM2013-2267