bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4583: A blocking antibody to HB-EGF inhibits the growth of tumor xenograft
Authors: Kimura Naoki , Taniguchi Kenji , Hirata Yuichi 
Published: June 2012

Abstract
Heparin-binding epidermal growth factor (HB-EGF), a member of the EGF family of growth factors, is widely expressed in many human cancers compared with normal tissues. HB-EGF is initially produced as a membrane-anchored form (pro-HB-EGF) and later processed to a soluble form (s-HB-EGF), which exert its biological activity through activation of EGFR and EGFR4. A key role of HB-EGF in the acquisition of malignant phenotypes has been well documented, such as tumorigenicity, invasion, metastasis, angiogenesis, and resistance to chemotherapy. In this study, we demonstrate the potential of an anti-HB-EGF mAb for cancer therapy by generating a potent blocking monoclonal antibody, HC-15. The HC-15 mAb recognized both forms of HB-EGF, pro- and s-HB-EGF. HC-15 efficiently blocked the binding of HB-EGF to EGFR-Fc in the ELISA. Furthermore, HC-15 substantially inhibited the HB-EGF-dependent proliferation of the EGFR expressing Ba/F3 transfectant lines. To investigate the potential of HC-15 for cancer therapy, the in vivo antitumor activity of HC-15 was tested. Significant growth inhibition by treatment of HC-15 (10mg/kg once a week) was observed in established human tumor models, such as ovarian cancer (MCAS), pancreatic cancer (BXPC-3), and breast cancer (MDA-MB-231) in athymic nude mice. Thus, we conclude that the anti-HB-EGF mAb HC-15 has strong anti-tumor activity in various models, supporting the inhibition of HB-EGF functions by mAb is useful in cancer treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4583. doi:10.1158/1538-7445.AM2011-4583
Abstract 4593: Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in athymic nude mice
Authors: Budhraja Amit , Gao Ning , Zhang Zhou , Son Young-Ok , Ding Songze , Hitron Andrew , Gupta Pooja , Shi Xianglin 
Published: June 2012

Abstract
Purpose of the study: To investigate the functional role of Akt and JNK signaling cascades in apigenin-induced apoptosis in human leukemia cells (in vitro) and anti-leukemic activity of apigenin in U937 xenografts (in vivo).
Experimental Design: Leukemia cells were treated with apigenin in dose and time dependent manners, after which apoptosis, caspases activation, Akt and JNK signaling pathways were evaluated by pharmacologic and genetic approaches. Parallel studies were also conducted in Jurkat, HL60 and normal peripheral blood mononuclear cells. In vivo anti-leukemic activity mediated by apigenin was evaluated using U937 xenograft mouse model.
Results: Exposure of apigenin caused pronounced increase in apoptosis in leukemia cells but not in normal peripheral blood mononuclear cells. Apigenin-induced apoptosis by inactivation of Akt with concomitant activation of JNK, cytochrome c release from mitochondria and caspases activation in dose and time dependent manners. Enforced activation of Akt by a constitutively active myristolated Akt prevented apigenin-induced JNK and caspases activation and apoptosis. Conversely, PI3K (phosphatidyl 3-kinase) inhibitor LY294002 and a dominant negative construct of Akt potentiated apigenin-induced apoptosis in leukemia cells. In addition, Akt kinase activity was diminished after exposure to apigenin in leukemia cells. Interruption of JNK pathway by pharmacologic (SP600125) and genetic (JNK1 siRNA) approaches showed marked reduction in apigenin-induced caspases activation and apoptosis in leukemia cells. Furthermore, in vivo administration of apigenin via intraperitoneal route resulted in attenuation of tumor growth in U937 xenografts accompanied by apoptosis.
Conclusions: Collectively, these findings suggested a hierarchical model of apigenin-induced apoptosis in human leukemia cells in which apigenin-induced Akt inactivation represents a primary event resulting in JNK activation and culminating in caspases activation and apoptosis. In addition, attenuation of tumor growth in U937 xenografts by apigenin raise the possibility that apigenin may have clinical implications for therapeutic intervention against leukemia.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4593. doi:10.1158/1538-7445.AM2011-4593
Abstract 4594: Grape seed extract induces apoptosis in human colorectal carcinoma through modulation of death receptors and anti-apoptotic molecules
Authors: Derry Molly M. , Agarwal Rajesh , Agarwal Chapla 
Published: June 2012

Abstract
Colorectal Cancer (CRC) is the second leading cause of cancer related deaths in the US. Diets rich in fruits and vegetables are shown to decrease CRC incidence by 40%, in part due to antioxidant and free radical properties of the polyphenolics present therein; grape seed extract (GSE) is one of the richest sources of these antioxidants. Oncogenic mutations that suppress apoptosis can lead to tumor initiation, progression, and metastasis; a major cause of conventional treatment resistance is due to apoptotic pathway defects. Accordingly, the strategies that target the mechanisms of apoptosis resistance in cancer cells provide the potential opportunities for cancer management. Herein we investigated the apoptotic effects of GSE and defined associated mechanisms in three human CRC cell lines, namely SW480, SW620 and HCT116, representing II-IV stages of CRC. Normal colon epithelial cells namely NCM460 was also included to establish GSE specificity, if any, towards CRC cells. A comparison of GSE activity in three CRC cell lines showed that almost three times higher GSE levels are needed for comparable cell death effect in SW480 versus SW620/HCT116 cells; cell treatments were accordingly adjusted for remainder studies. GSE treatment of SW480 cells at 25-100μg/mL resulted in a maximum of 55% apoptotic death at 48h; however, even 10-30μg/mL GSE treatments produced 53-57% apoptotic cell death in SW620 and HCT116 cell lines. At the molecular level, GSE induced DR4/5 up regulation, caspase-9, -3, -8, and PARP cleavage in all three cell lines indicating the involvement of both extrinsic and intrinsic apoptotic pathways in its efficacy. Furthermore, GSE treatment caused down regulation of anti-apoptotic proteins Bcl-2 and XIAP in SW480 cells only, but increased the levels of pro-apoptotic proteins such as Mcl-1s in all three cell lines. Importantly, GSE also increased the levels of p53 and its associated regulators namely p21, PUMA and Bak, suggesting their possible role in GSE-caused apoptotic death in HCT116 cell line. GSE treatment (25-100μg/mL) of NCM460 cells did not result in significant death compared to what was observed in three different human CRC cell lines, clearly showing its activity selectively in cancer cells. In conclusion, our findings further support the notion that GSE could be an effective chemopreventive and chemotherapeutic agent for colorectal.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4594. doi:10.1158/1538-7445.AM2011-4594
Abstract 4599: Apigenin intake suppresses IGF-I signaling in an autochthonous mouse model of prostate cancer
Authors: Shukla Sanjeev , Gupta Sanjay 
Published: June 2012

Abstract
Insulin-like growth factor-I (IGF-I) and its receptor (IR) plays an important role in prostate cancer development and progression. IGF-I binds to the IGF-IR that transduces signals to the nucleus and mitochondria primarily via the mitogen-activated protein kinase (MAPK) and PI3K/Akt pathways facilitating increased cell survival and proliferation. Agents that are capable of inhibiting IGF-signaling pathway might be useful in the prevention and/or therapy of prostate cancer. Apigenin, a common dietary flavonoid abundantly present in fruits and vegetables has shown remarkable cancer preventive and cancer therapeutic effects. The mechanisms underlying the cancer-protective effect remains elusive. We determined the role of IGF-signaling and its downstream and other associated events by apigenin using TRAMP model. TRAMP represents males spontaneously develop prostatic adenocarcinoma that progresses through multiple stages and exhibits both histological and molecular features similar to that of human prostate cancer. TRAMP males exhibit an increase in the level of serum IGF-I, uPA and VEGF; p-Akt (Ser473), p-ERK1 (T202/Y204) and p-ERK2 (T185/Y187) in the dorso-lateral prostate of TRAMP mice in age-dependent manner, compared to non-transgenic littermates. Oral intake of apigenin at 20- and 50- microg/mouse/day (gavaged in 0.2 ml vehicle containing 0.5% methyl cellulose and 0.025% Tween 20) was provided for six days per week for 20 weeks; whereas the third group received vehicle only and served as control. Apigenin intake by TRAMP mice from 8-28 weeks of age exhibited marked reduction in tumor growth with no signs of metastasis and also resulted in a significant decrease in the wet weight of dorso-lateral and ventral lobes of the prostate and genitourinary apparatus. Apigenin intake exhibited a marked dose-dependent reduction in the levels of IGF-I along with significant increase in the levels of IGFBP-3 in the serum of TRAMP mice. The modulation of IGF-I/IGFBP3 was associated with suppression of p-ERK1 (T202/Y204) and p-ERK2 (T185/Y187) and p-Akt (Ser473) levels measured in the tissue lysates from the dorso-lateral prostates of these mice. Furthermore, apigenin intake resulted in marked inhibition of the target genes regulating angiogenesis and metastasis, notably VEGF, uPA, MMP-2 and -9 in the mouse serum. Taken together, this study provides evidence that in vivo growth inhibitory effects of apigenin involve inhibition of IGF-I signaling axis in prostate cancer and further support the development of apigenin as a promising anticancer agent.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4599. doi:10.1158/1538-7445.AM2011-4599
Abstract 46: COSMIC: Enhancing the analysis of whole somatic mutant tumor genomes
Authors: Forbes Simon A. , Bindal Nidhi , Kok Chai Yin , Jia Mingming , Leung Kenric , Gunasekaran Prasad , Bamford Sally , Cole Charlotte , Teague Jon , Stratton Michael R. , Campbell Peter , Futreal P Andrew 
Published: June 2012

Abstract
COSMIC, the Catalogue Of Somatic Mutations In Cancer (http://www.sanger.ac.uk/cosmic), is a comprehensive web resource for the investigation of somatic mutations in human cancer with data curated and centrally combined from a variety of sources. Currently, point mutation data have been manually curated from the scientific literature on 89 genes, together with full mutation details on a further 57 fusion gene pairs (Release v50, Nov 2010), defined as known cancer genes in the Cancer Gene Census (http://www.sanger.ac.uk/genetics/CGP/Census). Further, in collaboration with the IARC TP53 database, COSMIC now contains the somatic mutation data for the key p53 tumor suppressor gene. Details of many large candidate gene screens, together spanning almost 20,000 genes have also been curated from three sources, the scientific literature, the Cancer Genome Project labs at the Sanger Institute, UK (CGP), and The Cancer Genome Atlas (TCGA) web portal. Finally, COSMIC now presents the results of 48 whole-genome screens, detailing 2689 genomic rearrangements, 1661 coding mutations and 55,440 non-coding mutations.
The COSMIC website is designed to allow easy and intuitive browsing of this data, in isolation or various combinations. As the amount and variability of data has increased, the methods of acquiring and interacting with the data have been enhanced. The COSMIC website now provides mining capabilities, with numerous specialization filters, graphically presenting selected data. A more extensive mining tool is the COSMIC Biomart, allowing selection of data using any definitions found in the COSMIC system.
With the increasing significance of genomic data in cancer, COSMIC has integrated with the two largest genome browsers, the Ensembl system and the UCSC cancer genomics browser; links are available from and to Ensembl, whilst per-tissue summaries are provided graphically in the UCSC browser. In addition, COSMIC has integrated its own genome browser, a version of ‘Gbrowse’, which provides custom genomic views of the majority of COSMIC data, together with CONAN copy number graphs, within the context of full genome annotations. Looking to the future, much novel global cancer genomics data will soon be made available via the ICGC data coordination centre. COSMIC is well placed to utilize this as a major new source of mutation information, maintaining COSMIC's position as a central resource in human cancer genetics.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 46. doi:10.1158/1538-7445.AM2011-46
Abstract 4602: Cholesterol and ezetimibe: Effects on tumor growth and survival outcomes: An interim analysis
Authors: Chu David I. , Masko Elizabeth M. , Poulton Susan H. , Pizzo Salvatore V. , Freedland Stephen J. 
Published: June 2012

Abstract
Introduction and Objectives: Prostate cancer (PC) is affected by cholesterol metabolism and cholesterol-mediating medications. Ezetimibe, a gut cholesterol-uptake inhibitor, inhibits angiogenesis in human PC xenografts when given as preventive therapy. We investigated the effect of ezetimibe on PC growth when given as treatment therapy.
Methods: We randomized 125 SCID mice into three initial diets: a high-fat, low-cholesterol diet (HFLC) (40% fat, 43% carbohydrates, 17% protein, 0.21% cholesterol), a high-fat, high-cholesterol diet (HFHC) (40% fat, 43% carbohydrates, 17% protein, 1.25% cholesterol), and a high-fat, high-cholesterol diet supplemented with ezetimibe (30mg/kg) (HFHC+Z). Mice were fed ad libitum. After two weeks, we injected 106 LNCaP cells into the flanks, with 5-10 mice/group serving as non-injected controls. At two weeks post-injection, half the injected and control mice in the HFHC diet group had ezetimibe added to their diet (HFHC+delayed Z). Tumor volumes and body weights were measured twice weekly. Mice were sacrificed once tumors reached 1000mm3. Body weights and tumor volumes were compared across groups using Kruskal-Wallis test. Interim survival outcomes for this on-going study up to 86 days post-injection were evaluated with Cox proportional hazards.
Results: At 1 day prior to injection, there were no significant differences in body weights across groups. At post-injection day (PD) 2, HFHC+Z mice with tumors were significantly lighter vs. all other mice (p=0.009). By PD 21, HFHC+delayed Z mice with tumors also became significantly lighter vs. the HFLC and HFHC mice with tumors (p&lt;0.001). At PD 86, all mice with tumors were significantly lighter than their control counterparts without tumors (all p&lt;0.013). Tumor volumes were not significantly different across groups (p=0.280). Likewise, survival was not significantly different across groups at PD 86 (p=0.125).
Conclusion: Preliminary evidence from this on-going study demonstrates that ezetimibe is associated with weight loss, but only in mice with PC xenografts. The administration of ezetimibe as preventive vs. treatment therapy does not appear to affect tumor growth or survival. Future studies to explore the interplay between cholesterol metabolism and PC include comparing serum levels of cholesterol, insulin, IGF-1, and IGFBP-3, and tumor markers of proliferation and angiogenesis including akt, pakt, mTOR, VEGF, HIF, CD31 (microvessel density) and ki67 (proliferation). Moreover, we are continuing to follow the mice for any differences in tumor growth or survival.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4602. doi:10.1158/1538-7445.AM2011-4602
Abstract 4619: Chemopreventive activities of the dark-color fruit ‘jamun’, the Indian blackberry
Authors: Gupta Akash , Aqil Farrukh , Kausar Hina , Munagala Radha , Jeyabalan Jeyaprakash , Sharma Ramjee , Singh Inder P. , Gupta Ramesh C. 
Published: June 2012

Abstract
Colored fruits, particularly berries, are emerging as highly chemoprotective because of their antioxidant, anti-proliferative and anti-inflammatory activities. In this study, we investigated the chemoprotective potential of Eugenia jambolana Lam., commonly known as ‘jamun’ or Indian blackberry. Jamun, a widely available fruit in India and other Asian countries, has also been used in the treatment of various ailments, including diabetes mellitus. To determine its antioxidant potential, jamun pulp was collected from freshly harvested fruits, dried, and the powder was extracted with acidic ethanol, and enriched by amberlite XAD7/HP20 (1:1) column chromatography. The pulp powder was found to contain 0.54% anthocyanins, 0.17% ellagic acid/ellagitannins and 1.15% total phenolics using standard assays. HPLC analysis of acid-hydrolyzed extract showed the presence of five anthocyanidins – malvidin, petunidin, delphinidin, cyanidin and peonidin. The unhydrolyzed extract was found to have significant antioxidant activity as reflected by high ORAC value (1,445±64 μmol of TE/g) as well as high ABTS- and DPPH-scavenging activities, and ferrous ions-chelating activity; the acid-hydrolyzed extract showed higher activity than unhydrolyzed extract. Since some of the jamun bioactives (ellagitannins and anthocyanidins/anthocyanins) have significant antiproliferative activity, we also analyzed these extracts for their antiproliferative potential using MTT assay against human lung cancer A549 cells in cell culture. The hydrolyzed jamun extract showed significant antiproliferative activity (IC50=79 µg/mL). However, unhydrolyzed extract showed almost no activity. These data suggest that the antiproliferative activity may result from anthocyanidins (present in the hydrolyzed extract) rather than anthocyanins (present in unhydrolyzed extract). Together, our data show high antioxidant, and antiproliferative activities in jamun pulp and may be a viable candidate for chemoprevention of lung cancer (Supported from Agnes Brown Duggan Endowment).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4619. doi:10.1158/1538-7445.AM2011-4619
Abstract 4620: Development of honokiol for the prevention of UVB-induced skin tumor development
Authors: Chilampalli Shivani , Averineni Ranjith , Xie Jiashu , Perumal Omathanu , Dwivedi Chandradhar 
Published: June 2012

Abstract
Skin cancer is the most prevalent of all cancers and its incidence is expected to increase substantially. UVB is major etiologic factor in the skin cancer development. Honokiol, a plant ligan isolated from bark and seed cones of Magnolia officinalis, has been shown to have chemopreventive effects on UVB-induced skin cancer development in our laboratory. The objectives of this investigation are to study chemopreventive effects of dose response of honokiol on UVB-induced skin tumor development in SKH-1mice and to prepare topical formulations of honokiol that deliver effective concentration of drug locally. Female SKH-1 mice were divided into 4 groups. Group 1 received acetone one hour before UVB treatment; Group 2, 3 and 4 received honokiol (0.2 ml of 30, 45 and 60 μg in acetone, topical) before each UVB treatment. Mice were treated with UVB dose of 30 mJ/cm2/day for 25 weeks. Tumor counts and group weights were taken weekly. Honokiol pretreated groups resulted in 36-78% reduction in tumor multiplicity compared to control. Honokiol pretreatment (60 μg) decreased tumor incidence by 40 %. Topical formulation of honokiol gel was prepared by using carbomer 940 as base and propylene glycol as penetration enhancer. Drug content and content uniformity were determined. Release studies and permeation studies were studied in detail.
This study is supported by Translational Cancer Research Center funded as 2010 Research Initiative Center by the State of South Dakota
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4620. doi:10.1158/1538-7445.AM2011-4620
Abstract 4622: Determination of pyranocoumarin compounds decursin, decursinol angelate and decursinol simultaneously in mouse plasma and tumor tissue by liquid-liquid extraction and HPLC
Authors: Li Li , Zhang Jinhui , Zhang Yong , Shaik Ahmad Ali , Wang Lei , Xing Chengguo , Kim Sung-Hoon , Lü Junxuan 
Published: June 2012

Abstract
Pyranocoumarin compound decursin and its isomer decursinol angelate (DA) are the major chemical components of the root of Angelica gigas Nakai (AGN, Korean Angelica), a major traditional medicinal herb. Recently, AGN has been shown to exhibit anti-tumor activities by our collaborative team. Decursinol has been identified as a major metabolite of decursin and DA in vivo by us and others, but another group has published very controversial results. To better define the mechanisms of in vivo action for AGN, pharmacokinetic studies are essential. In this study, we set up a practical method for the concurrent analysis of decursin, DA and decursinol in mouse plasma and tumor tissues by liquid-liquid extraction and HPLC-UV. In brief, plasma or tumor homogenate (0.1-0.2 ml) spiked with 1μg chrysin as internal standard (IS) was extracted directly with ethyl acetate. After extraction, decursin, DA and decursinol were quantitated by HPLC with UV detection at 330 nm. The method was validated in terms of recovery, lower limit of quantitation and linear range. The extraction efficiency for spiked decursin/DA and decursinol at 1 µg/ml was 90.1±3.2 % and 90.3±1.8% in mouse plasma, respectively. The lower limit of quantitation (LOQ) was approximately 0.25 μg/mL for decursin/DA, and 0.2 μg/mL for decursinol in mouse plasma. The linear range of the method was 0.25 -25 µg/ml and 0.2-50 µg/ml in mouse plasma for decursin/DA and decursinol, respectively.
In a pilot pharmacokinetic study, male C57BL/6 mice were given a single dose of 4.8 mg decursin/DA (∼240mg/kg) per mouse either by gavage or intraperitoneal injection in 0.2 mL vehicle of ethanol:PEG400:Tween80:5% glucose (3:6:1:20). Maximum plasma concentrations for decursin/DA and decursinol were found to be 34.2 and 324 µM respectively when D/DA was administered via intraperitoneal injection and to be 1.7 and 60.7 µM via gavage. These findings further confirmed that decursinol was one of the major metabolites of decursin/DA in vivo. In athymic nude mouse xenograft study, the mice were given intraperitoneal injection of decursin/DA at a dose of 1mg (∼40mg/kg) daily, 5 days per week, for 7 weeks. The decursin/DA and decursinol concentration was 1.5 and 10μg/g, respectively, in the tumor tissue.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4622. doi:10.1158/1538-7445.AM2011-4622