bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5517: Polymeric nanogel-based treatment regimen for enhanced efficacy and sequential administration of synergistic drug combination in pancreatic cancer
Authors: Soni Kruti S. , Hollingsworth Michael A. , Radhakrishnan Prakash , Bronich Tatiana K. 
Published: August 2015

Abstract
Pancreatic cancer (PC) is one of the most lethal malignancies, due to aggressive tumorigenicity, early metastasis and development of drug resistance to standard care chemotherapy. Since its approval in 1997, Gemcitabine has been the first-line treatment for advanced disease. However, there is no standard second-line therapy after Gemcitabine failure. The combination of Gemcitabine with Cisplatin (CDDP) has been explored in clinical trials for metastatic disease and our preliminary in vitro studies with the free drugs on T3M4 Simple Cells (COSMC deleted cells) showed that synergy of the combination is schedule-dependent, and Gemcitabine administration followed by CDDP showed the most potent cytotoxic activity. However, this combination proved to be only marginally effective in actual practice due to combined increased toxicity of both the agents. We have shown that encapsulation of CDDP in polymeric nanogels with cross-linked ionic cores enhanced its tumor accumulation and improved its safety profile. Additionally, sustained release profile of CDDP from nanogels allows for the administration of free Gemcitabine and CDDP loaded nanogels in a single injection while still retaining schedule-dependent synergy of the combination. Pancreatic ductal adenocarcinoma cells are known to express truncated O-glycans (Tn and STn antigens) and it is anticipated that decorating the nanogels with an antibody directed against this antigen will further enhance their uptake by tumor cells while reducing off-target accumulation.
Citation Format: Kruti S. Soni, Michael A. Hollingsworth, Prakash Radhakrishnan, Tatiana K. Bronich. Polymeric nanogel-based treatment regimen for enhanced efficacy and sequential administration of synergistic drug combination in pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5517. doi:10.1158/1538-7445.AM2015-5517
Abstract 5536: KB-164, a novel and highly potent Src family kinase inhibitor, reduces cancer cell invasion and abrogates downstream oncogenic pathways in triple negative breast cancer
Authors: Gilani Rabia A. , Brandvold Kristoffer R. , Bao Li Wei , Phadke Sameer , Steffey Michael E. , Soellner Matthew B. , Merajver Sofia D. 
Published: August 2015

Abstract
Src is a non-receptor tyrosine kinase, which acts as an integrator of diverse signaling pathways used by cancer cells for cell proliferation, migration and metastasis. Recent interest in developing target specific therapy for improved benefits with manageable toxic effects has sharply increased the interest in testing new Src family kinase inhibitors for their potential anticancer therapeutic properties.
In this study, we sought to investigate the chemical characteristics and the biological effects of the novel Src family kinase inhibitor KB-164, in Src expressing triple negative breast cancer cells. We show that KB-164 acts as a potent Src kinase inhibitor (IC50 1.3 nmol/L) in MDA-MB 231 cells, 100-fold more potent than the most widely used Src family kinase inhibitor dasatinib. At concentrations of 50nmol/L, KB-164 led to complete inhibition of Src activation for 48 hours. Analysis of downstream effectors of Src revealed that treatment with KB-164 inhibits the phosphorylation of several oncogenic pathways i.e. EGFR, ERK1/2, P38MAPK and AKT. A dramatic decrease in cancer cell motility and invasion was observed on treatment with KB-164 in both SUM 149 and MDA-MB 231 triple negative breast cancer cell lines. We also show that triple negative breast cancer cells derived from the patients are equally sensitive to growth inhibition by KB-164 within an IC50 of 1.8-nmol range. No cytotoxicity was observed both in vitro (18 micro mol/L in normal human mammary epithelial cells) and in vivo (70mg/kg in mice). Our findings indicate that KB-164 inhibits signaling pathways involved in controlling tumor cell proliferation and survival, suggesting that KB-164 might prove to be a promising therapeutic agent for breast cancer.
Citation Format: Rabia A. Gilani, Kristoffer R. Brandvold, Li Wei Bao, Sameer Phadke, Michael E. Steffey, Matthew B. Soellner, Sofia D. Merajver. KB-164, a novel and highly potent Src family kinase inhibitor, reduces cancer cell invasion and abrogates downstream oncogenic pathways in triple negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5536. doi:10.1158/1538-7445.AM2015-5536
Abstract 5542: Flaxseed and its lignan component protect from asbestos-induced inflammation in mice
Authors: Albelda Steven M. , Pietrofesa Ralph A. , Menges Craig W. , Testa Joseph R. , Christofidou-Solomidou Melpo 
Published: August 2015

Abstract
Introduction/Background: Malignant mesothelioma (MM) is a highly lethal form of thoracic cancer with high mortality and poor treatment options. Development of MM has been linked directly to exposure to asbestos fibers, but with a long latency period. Recent studies have indicated that the pathogenesis of asbestos-induced cancers is due, in part, to chronic inflammation and oxidative tissue damage caused by persistent asbestos fibers. Whole grain flaxseed (FS) has known antioxidant, anti-inflammatory and cancer chemopreventive properties. Rationale: As a prelude to future chemoprevention studies, we tested the ability of oral FS and its lignan component, FLC which is enriched in the lignan secoisolariciresinol diglucoside (SDG), to prevent acute asbestos-induced inflammation and inflammatory cytokine release in MM-prone Nf2+/mut;Cdkn2a+/mut mice. Methods: Mice were given a single ip bolus of 400 mM of crocidolite asbestos. They were then placed on 10% FS or 10% FLC supplemented diets 1 day prior (-1) to or after (+1) asbestos instillation. All mice were evaluated 3 days after injection of asbestos for abdominal inflammation and proinflammatory cytokine release. The Nf2+/mut;Cdkn2a+/mut model was selected as it develops an accelerated form of MM when exposed to asbestos. Results: Using liquid chromatography and tandem mass spectrometry (LC/MS/MS), we showed that systemic levels (plasma) of flaxseed lignan metabolites (such as the mammalian lignans Enterolactone (EL) and Enterodiol (ED)) were comparable to those in other mouse models where FS was shown to be an effective chemopreventive agent. The numbers of macrophages (MF) and neutrophils (PMN) in peritoneal lavage fluid indicated that both FS and FLC blunted acute abdominal inflammation induced by asbestos. In addition, the levels of pro-inflammatory cytokines TNF alpha and IL-1 beta in lavage fluid were also decreased by the dietary agents. Conclusions: Our findings suggest that the known chemopreventive properties of FS and its lignan component appear to reduce short-term asbestos-induced inflammation and may thus prove to be a promising dietary agent in the chemoprevention of MM.
Funding: This study was supported in part by Penn's SRP Center Grant (P42 ES027320), “Asbestos fate, exposure, remediation and adverse health effects” from the National Institute of Environmental Health (NIEHS) and 1R03CA180548-02 (MCS).
Citation Format: Steven M. Albelda, Ralph A. Pietrofesa, Craig W. Menges, Joseph R. Testa, Melpo Christofidou-Solomidou. Flaxseed and its lignan component protect from asbestos-induced inflammation in mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5542. doi:10.1158/1538-7445.AM2015-5542
Abstract 5544: Attempts to synthesize 5,7-dihydroxy-3H-1,2-dithiolo[4,3-d]- pyrimidine, M-47, a potential new treatment for drug- resistant breast cancer
Authors: Marasco Canio J. , Dunn Joseph A. , Pera Paula J. , Macubbin Alexander E. 
Published: August 2015

Abstract
M-47, 5,7-Dihydroxy-3H-1,2-dithiolo[4,3-d]pyrimidine, represents a novel class of antineoplastic agents both in structure and apparent mechanism of action. The synthesis of M-47 has been shown to be problematic. Mass spectroscopy and HPLC suggest the presence of certain oxidative byproducts in minor quantities along with the desired analog. Repeated efforts to purify M-47 via crystallization, extraction, chemical modification, and various forms of chromatography have failed. Although enrichment of the sample in excess of 90% is possible, absolute purity has not been achieved. Despite the presence of minor impurities this analog was tested against a variety of cancer cell lines in vitro. Interestingly, M-47 displayed equipotent activity against certain breast cancer lines and their multidrug resistant progeny Furthermore, in vitro testing of various ratios of M-47 with its oxidative byproducts indicated that they possessed similar IC50's suggesting that cellular oxidation of M-47 might be a necessary step in its cytotoxic pathway. The profound activity of M-47, especially against drug-resistant tumor cells, warrants further investigation into the chemistry of these compounds, their biological activity and their possible mechanism of action.
Note: This abstract was not presented at the meeting.
Citation Format: Canio J. Marasco, Joseph A. Dunn, Paula J. Pera, Alexander E. Macubbin. Attempts to synthesize 5,7-dihydroxy-3H-1,2-dithiolo[4,3-d]- pyrimidine, M-47, a potential new treatment for drug- resistant breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5544. doi:10.1158/1538-7445.AM2015-5544
Abstract 5547: Anti-proliferative activity of hydnocarpin, a natural lignan, is associated with the inhibition of Wnt/β-catenin signaling pathway via axin turnover in colon cancer cells
Authors: KIM Won Kyung , LEE Min Ai , PARK Hyen Joo , HONG Ji-Young , KANG Sam Sik , LEE Sang Kook 
Published: August 2015

Abstract
Abnormal activation of the canonical Wnt/β-catenin pathway and up-regulation of the β-catenin/T-cell factor (TCF) response to transcriptional signaling play critical roles early in colorectal carcinogenesis. Therefore, the Wnt/β-catenin signaling is considered an attractive target for cancer chemotherapeutic of chemopreventive agents, natural compounds were evaluated for β-catenin-mediated transcriptional activity. Hydnocarpin (HC), a natural lignan from Lonicera japonica was identified as a promising candidate because it effectively inhibited β-catenin/TCF reporter gene (TOPflash) activity. HC also exhibited potent growth inhibition of SW480 human colon cancer cells. Further investigation of HC on the regulation of the Wnt/β-catenin signaling revealed that HC had minimal effect on GSKβ and CK1α, while the protein levels of both axin1 and axin2 were remarkably increased by HC treatment. In addition, the interaction of axin and β-catenin by HC was significantly increased as analyzed by immunoprecipitation assay. These events led to up-regulation of the β-catenin destruction complex formation and phosphorylation of β-catenin. To further explore the role of axin1 up-regulation by HC in the mechanism of action of Wnt inhibitory effects on SW480 cells, siRNA experiments were conducted. The growth inhibitory effects of HC on SW480 cells were abolished by axin1 siRNA, implying that HC inhibited the Wnt/β-catenin signaling in an axin-dependent fashion. These finding suggests that HC might be a novel Wnt inhibitor and has a potential of signaling regulator in β-catenin-mediated signaling pathways.
Citation Format: Won Kyung KIM, Min Ai LEE, Hyen Joo PARK, Ji-Young HONG, Sam Sik KANG, Sang Kook LEE. Anti-proliferative activity of hydnocarpin, a natural lignan, is associated with the inhibition of Wnt/β-catenin signaling pathway via axin turnover in colon cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5547. doi:10.1158/1538-7445.AM2015-5547
Abstract 555: A workflow for enrichment and whole genome amplification (WGA) of circulating tumor cells (CTCs) for next generation sequencing
Authors: Nisic Merisa , Hao Sijie , Harouaka Ramdane , Zheng Si-Yang 
Published: August 2015

Abstract
Metastasis is the leading cause of cancer deaths. Circulating tumor cells (CTCs) are thought to be responsible for the seeding of metastases. These tumor cells are heterogeneous with variation occurring at the single-cell level. Using a flexible micro spring array (FMSA) device for label-free mechanical enrichment of CTCs from whole blood samples, we established a workflow from isolation followed by whole genome amplification (WGA) and finally sequencing of circulating tumor cells. Briefly, circulating tumor cells were collected from the FMSA using the Zeiss Laser Capture Microdissection System. Isolated cells underwent whole genome amplification using a commercial WGA kit. The quality of the amplified genomic DNA was analyzed using the TaqMan® Real-Time PCR Assays. Specific loci were then amplified with the Ion AmpliSeq™ Cancer Hotspot Panel v2 and sequenced using the Ion PGM™ System. These studies were performed to understand the genomic heterogeneity observed in circulating tumor cells.
Citation Format: Merisa Nisic, Sijie Hao, Ramdane Harouaka, Si-Yang Zheng. A workflow for enrichment and whole genome amplification (WGA) of circulating tumor cells (CTCs) for next generation sequencing. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 555. doi:10.1158/1538-7445.AM2015-555
Abstract 5552: Medicinal plants show anticancer splicing activity of apoptotic genes
Authors: Dlamini Zodwa , Bates David 
Published: August 2015

Abstract
Oncogenesis is associated with splicing switches and a disruption of splicing regulation being specific for cancer formation and tumour progression. An association between differential expression of splicing isoforms and tumour progression has been shown for several proteins, such as MDM2 and survivin. Currently the analysis of cancer-specific alternative splicing is a promising step forward in basic and translational molecular biology. Traditional medicine has a long history and is still the major source of medicine in developing countries. Approximately 70% of the South African population consults traditional healers, perpetuating the need for scientific appraisal of traditional medicine as a means to establish its efficiency and safety Also, pharmacological and phytochemical insights into several plants have led to the discovery of novel chemicals and therefore novel drugs. Alternatively, such novel chemical structures can serve as lead compounds/templates for the design of new drugs. The aim was to ascertain if the South African medicinal plants have anticancer splicing activity. 10c cells were treated with Tulbhaghia violacea and Cotyledon orbiculata, followed by mRNA extraction and RT-PCR. The results showed that Tulbhaghia violacea and Cotyledon orbiculata extracts have anti-cancer splicing activity on the BCLX and the AXL apoptosis genes. Additionally Cotyledon orbiculata extract has an anticancer splicing activity of the angiogenesis gene VEGF165. VEGF Elisa also confirmed the VEGF165 VEGF165b splicing switch. We have shown that South African medicinal plants have anti-cancer splicing activity. The anti-cancer splicing activity of the VEGF gene by Cotyledon orbiculata could mean that this extract has both angiostatic and apoptotic anti-cancer activities. We are continuing to screen more medicinal plants and will select those extracts with anti-cancer splicing activity for further studies. These further studies should identify numerous splicing pathways and completely elucidate the splicing target compounds that may serve as novel anti-cancer drugs or lead compounds.
Note: This abstract was not presented at the meeting.
Citation Format: Zodwa Dlamini, David Bates. Medicinal plants show anticancer splicing activity of apoptotic genes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5552. doi:10.1158/1538-7445.AM2015-5552
Abstract 5562: BreastDefend enhances the effects of tamoxifen in estrogen receptor-positive human breast cancer in vitro and animal models in vivo
Authors: Cheng Shujie , Alvarado Mark , Loganathan Jagadish , Castillo Victor , Sandusky Georg , Eliaz Isaac , Sliva Daniel 
Published: August 2015

Abstract
In this study we evaluated the combined effects of the natural product/dietary supplement BreastDefend (BD) and tamoxifen (TAM) on MCF-7 estrogen receptor-positive (ER+) human breast cancer cells in vitro and an orthotopic mouse model in vivo. BD has been studied previously in preclinical models, and shown to exert significant effects on MDA-MB-231 triple-negative breast cancer cells. The proliferation of MCF-7 cells was evaluated using MTT assays, whereas the expression of genes involved in the molecular mechanisms of cancer was evaluated using DNA microarrays. MCF-7 cells were stimulated with estradiol (10 nM) and treated with TAM (1 μM), BD (10 μg/ml), and the combination of TAM and BD for 3 days and 6 days. Compared with control, BD enhanced the anti-proliferative activity of TAM significantly (P &lt; 0.05), and the combination of BD and TAM induced apoptosis. The results of DNA microarray analyses suggested that the pro-apoptotic activity of BD and TAM in MCF-7 cells was associated with the significant upregulation of BRAF (an oncogene that can block proliferation and induce apoptosis) and downregulation of BCL2 (an apoptosis inhibitor) and FN1 (fibronectin, a glycoprotein involved in tumorigenesis and metastasis) expression. In the orthotopic model MCF-7 cells were implanted into the mammary fat pads of female ovariectomized nude mice (n = 12-13). The mice received subcutaneous pellets that released estradiol and TAM, whereas BD was administered orally via intragastric gavage. All groups, including control, received estradiol. The combination of BD and TAM suppressed tumor size in vivo markedly compared with the BD and TAM alone groups. The inhibition of tumor growth was associated with the induction of the cell cycle inhibitor protein p21 in MCF-7-generated breast tumors. In summary, this study suggests that BD could be considered for use in clinical studies as an adjuvant therapy in conjunction with TAM for the treatment of ER+ human breast cancer.
Citation Format: Shujie Cheng, Mark Alvarado, Jagadish Loganathan, Victor Castillo, Georg Sandusky, Isaac Eliaz, Daniel Sliva. BreastDefend enhances the effects of tamoxifen in estrogen receptor-positive human breast cancer in vitro and animal models in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5562. doi:10.1158/1538-7445.AM2015-5562
Abstract 5565: Antitumor activities of psammaplin A analogues in human lung cancer cells
Authors: Shin Yoonho , Hong Suckchang , Shin Jongheon , Park Hyeung-geun , Lee Sang Kook 
Published: August 2015

Abstract
Histone deacetylase inhibitors (HDACi) are considered to be potential candicates for cancer therapeutic agents. HDACi suppresses the progression of tumorigenesis through epigenetic regulation of target protein acetylation. Psammaplin A (PsA), originated from a marine product Pseudoceratina purpurea, also showed a potential HDAC inhibition. Based on the potential anticancer activity of PsA, various PsA analogs were designed and synthesized to explore novel candidates in the development of anticancer agents. Among compounds tested, a β-napthyl-derivertive of PsA (compound 30) exhibited a strong growth-inhibitory activity against human lung cancer cells and the activity was comparable to PsA. Compound 30 also effectively inhibited HDAC and up-regulated the level of ac-Histone3, p-AKT, p-ERK in human A549 lung cancer cells. In in vivo xenograft animal model implanted A549 cells, the administration of compound 30 intraperitoneally for 35 days exhibited a potential growth inhibitory activity of the tumor (47.6% inhibition at 30 mg/kg). The immunohistochemical analysis of tumor tissues also revealed the inhibition of the cell proliferation biomarker Ki-67 expression by compound 30. Taken together, these data suggest that a β-napthyl analog of PsA has the potential antitumor activity and thus to be prioritized in the development of cancer chemotherapeutic agents.
Citation Format: Yoonho Shin, Suckchang Hong, Jongheon Shin, Hyeung-geun Park, Sang Kook Lee. Antitumor activities of psammaplin A analogues in human lung cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5565. doi:10.1158/1538-7445.AM2015-5565
Abstract 5568: Inhibitory Effect of Partial Electron Decoupling Agents as an Alternate Therapy for Cancer
Authors: Bagasra Omar , Heslop Kareem , Livingston Krystal , Corbett Keneisha , Ejiawoko Amarachi O. , Sealey Leanna 
Published: August 2015

Abstract
Cancer therapies are generally non-specific for cancer cells and affect all cells in the body, resulting in severe side effects. We are working on an alternate method to present and treat cancer. Hypothesis: All replicating cells require energy in the forms of ATP and row material to reproduce. Cancer in a human body generally is the most energy consuming foci; therefore, it will be logical to down regulate the highest energy output pathways that do not harm the human being treated for a cancer. Two of the most prevalent cancers in are adenocarcinomas of prostate and breast. We hypothesized that if we treat cancer cells to a partial electron transport inhibitor that results in reduction in total ATP output it may significantly reduce cancer cell proliferation without interfering with normal functioning of other physiologic and immune functions. We chose Amygdalin (D-mandelonitrile-β-gentiobioside) which is found in seeds of prunasin family plants, such as peaches, apricots, almonds, apples, and other rosaceous plants and have been used as a traditional alternate medicine for treating terminal cancers and other illnesses. We evaluated the optimal dose that can inhibit various breast and prostate cancer cell lines as well two stem cell lines derived from neuroblastomas. We determine that cancer cell line and stem cell line proliferation rates were significantly inhibited 0.9 μM concentration of Amygdalin. This level of Amygdalin can be achieved by consuming 4-6 bitter almond and 2-3 apricot seed daily. In addition, we observed that Amygdalin induced apoptosis in the prostate and breast cancer cell lines.
Citation Format: Omar Bagasra, Kareem Heslop, Krystal Livingston, Keneisha Corbett, Amarachi O. Ejiawoko, Leanna Sealey. Inhibitory Effect of Partial Electron Decoupling Agents as an Alternate Therapy for Cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5568. doi:10.1158/1538-7445.AM2015-5568