bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5537: Quantitative multiplexed SRM analysis of oncogenic receptors in FFPE colorectal carcinoma tissue
Authors: Hembrough Todd , Thyparambil Sheeno , Liao Wei-Li , Darfler Marlene , Krizman David , Adams Richard , Burrows Jon 
Published: August 2012

Abstract
Multiple receptor tyrosine kinases are the target of either approved drugs (Her2, EGFR) or robust clinical development efforts (cMet, IGF1R, Her3, etc). In many cases initial drug response is followed by resistance and tumor progression. There are many mechanisms which have been proposed for this including co-expression of alternate RTKs that continue to stimulate tumor growth in the presence of EGFR/Her2 inhibition. Because of the potential that co-expression of oncogenic receptors mediates resistance in these clinical trials, we have developed a panel of new SRM assays which measure the expression of these critical RTKs in multiplex from FFPE tissues. These assays are based on the Liquid Tissue®-SRM technology platform. This approach enables relative and absolute quantification of proteins and their phosphorylation status directly in formalin fixed paraffin embedded (FFPE) tissue. Here we describe the quantitative multiplexed analysis of EGFR, IGF1R and cMet expression in a cohort of 75 archival FFPE colorectal cancer tumors from Cetuximab treated patients. This analysis identified 7 different fingerprints of expression of these three targets. Since each of these targets has either approved inhibitors, or highly active clinical development programs, we are hopeful that this analytical approach can help to identify patients who are most likely to respond to single or combination therapies of RTK inhibitors Follow up studies are underway to expand the RTK- multiplex, repeating EGFR, IGF1R and cMet and adding Her2, Her3, Her4, DR5, cSrc, and other drug targets into the multiplex. Our intention is to use this broader multiplex to re-analyze these patients and attempt to correlate the multiplexed expression of these targets with drug response data.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5537. doi:1538-7445.AM2012-5537
Abstract 5542: Gene expression and genomic DNA stabilization in whole blood stored at room temperature
Authors: Liberal Vasco , Wilkinson Steven P. , Stassinopoulos Angela , Huang Winnie , Whitney Scott , Shireen Lutfunnessa , Ohgi Sharron , Muller Rolf , Muller-Cohn Judy 
Published: August 2012

Abstract
Genomic and mitochondrial DNA and gene expression profiles from blood samples are increasingly being used to diagnose specific diseases, including cancer, monitor disease progression and assess patient responses to medical treatment. However, such applications require reliable preservation of total RNA and DNA in patient samples during collection, transport and storage. Numerous agents threaten DNA and RNA profiles in collected blood samples, including nucleolytic attack, oxidative damage and hydrolysis. Such damage can severely disrupt genotyping and DNA sequencing efforts. Transcription profiles are highly dynamic and can change rapidly during and after blood collection using current methods, potentially affecting interpretation of the expression analysis, and ultimately lead to inadequate treatment options. In this study, we compare freezer storage with room temperature stabilization formulations, DNAgard Blood and PAXgene Blood DNA, in their capacities to preserve genomic DNA integrity in human whole blood for 8 months. In a separate analysis, we compare freezer storage with room temperature stabilization formulations, PAXgene Blood RNA and Biomatrica formulation DRG, in their capacities to stabilize RNA in whole blood samples. We assess changes in the relative expression of a panel of 34000 genes in whole blood specimens over the course of 7 days using RT-qPCR and the Human HT-12 Bead Array (Illumina). Our results demonstrate that room temperature blood storage is a valid alternative to cold-storage for preserving gDNA for more than a year, and RNA for at least 7 days.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5542. doi:1538-7445.AM2012-5542
Abstract 5689: Anti-E2F-1 PEGylated liposomal encapsulated peptide regresses human small cell lung cancer & lymphoma xenografts
Authors: Xie Xiaoqi , Banerjee Debabrata , Minko Tamara , Johnson-Farley Nadine , Kerrigan John E. , Ercikan-Abali Emine , Scotto Kathleen W. , Bertino Joseph R. 
Published: August 2012

Abstract
The E2F family of transcription factors is critical to large number of key cellular processes, including replication, DNA repair, and differentiation. E2F-1 is unique among the E2F family of transcription factors in that it can act as a tumor suppressor or as an oncogene, depending on the cellular context. Given the critical functions of E2F target genes in replication, and differentiation, it is perhaps not surprising that dysregulation of E2Fs has been associated with the cancer phenotype. E2F-1,2 and-3, “activating” E2Fs, function as heterodimers with DP proteins and are regulated by the retinoblastoma protein. E2F-1 and 3 are over expressed in many human tumors and overexpression (suggesting oncogene addiction) is associated with a poor prognosis. We have used phage display to obtain peptides that bind tightly to the E2F consensus promoter recognition sequence. When one of these peptides was coupled to a modified penetration sequence to enhance uptake, the penetratin- peptide (PEP) potently inhibited some but not all malignant cell lines. Modeling studies and ChIP studies showed that part of the pentratin sequence was involved in the binding of the PEP to the E2 F1 promoter. The PEP down-regulated E2F-2 and 4, as well as E2F-1, and-down stream targets of E2F-1. The small cell lung carcinoma (SCLC) cell line and the Ramos cell line (Burkitt lymphoma) were sensitive to low micromolar concentrations of the PEP, and apoptosis was seen within 6 h. These cell lines have mutant p53, and over express E2F-1 and cMyc and BCL2, and are “oncogene addicted”. Normal cells (human bone marrow CD34+ hematopoeitic stem cells, human marrow mesenchymal cells and MEFs), were insensitive to high concentrations of the PEP. When encapsulated in PEGylated liposomes, the PEP caused marked regression of advanced SCLC xenografts in mice without appreciable toxicity. These results prompt us to explore further preclinical development of the PEP for tumor therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5689. doi:1538-7445.AM2012-5689
Abstract 5710: Effective siRNA delivery through specific targeting of tumor
Authors: Jun Eun Sung , Kim Jong-Ho , Lee Byung-Heon , Park Rang-Woon , Kim In-San 
Published: August 2012

Abstract
The siRNA has been expected to apply for several diseases such as cancer since siRNA specifically silences the disease-associated genes. However, effective gene carriers should be developed to overcome the low siRNA stability in vivo, form stable complexes and facilitate intracellular uptake of siRNA. Here, we have investigated tumor targetable oligopeptide carrier including tumor-homing peptide, AP-1, and rich positive peptide, nine arginines, for systemic siRNA delivery. Phage display technique is a promising tool for selecting peptides or proteins with specific binding properties from a lot of variants. AP-1 peptide can bind with interleukin-4 receptor which expressed on surface of several human cancer cells like MDA-MB231. Arginine rich peptides have been widely used for forming complex with DNA, which promote efficient transfection in various mammalian cells. Oligopeptides formed ionic complex with siRNA at 150 nm size and these peptide/siRNA complexes were transfected in MDA-MB231. Under in vitro silencing experiments, peptide/siRNA complexes did silencing of Dronpa gene as similar to lipofectamine/siRNA complexes, which were observed by fluorescent microscope, flow cytometry, and western blotting analysis. For in vivo experiments, we prepared tumorbearing mice by inoculation of Dronpa-MDA-MB231 cells (Dronpa-stable cells). Tumor targetable oligopeptide/siRNA complexes were administrated through tale vein when tumor volume reached at 50 mm3 - we observed fluorescent signals of Dronpa in tumor. In tumor targetable oligopeptide/siRNA-treated mice, weak signals of Dronpa were observed compared with free siRNA-treated mice. These results revealed the promising potential of our oligopeptide carrier as a stable and effective siRNA delivery system for cancer treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5710. doi:1538-7445.AM2012-5710
Abstract 5717: The Poly (ADP-Ribose) Polymerase-1 Inhibitor, AZD2281, enhances radiation response of breast cancer cells by inhibiting DNA repair
Authors: Mehta Meghna , Munshi Anupama 
Published: August 2012

Abstract
PARP-1 is a nuclear enzyme essential for base excision repair (BER), SSB, and possibly other DNA repair processes and an important damage sensor. It has been identified as a synthetic lethal target in BRCA1/2 breast cancers. PARP-1 is activated after binding DNA strand breaks and uses NAD+ as a substrate to form long branched polymers of poly(ADP-ribose) (PAR). PARP-1 mediated poly(ADP-ribosylation) recruits various nuclear acceptor proteins, such as XRCC1, histones, and PARP-1 itself, to assemble other repair complexes to execute DNA repair. As a result, PARP inhibitors are being developed for cancer therapy due to their ability to sensitize cells to DNA-damaging agents. Thus, in this current study, we hypothesized that enhanced radiosensitivity of breast cancer may be achieved by combining ionizing radiation (IR) with the PARP inhibitor, AZD2281. We studied the effects of combined treatment of radiation and AZD2281 on three human breast cancer cell lines, MCF-7, MDA-MB-231 and Hs578t. Cells were treated either with vehicle alone or with AZD2281 (4μM for 24hrs for MCF-7; 2μM for 24hrs for the MDA-MB-231 and Hs578t cells). Clonogenic cell survival assay showed that AZD2281 enhanced tumor cell radiosensitivity with the survival factor at 2Gy (SF2) being reduced from 26%, 52.8%, and 51.5% in vehicle treated to 18.5%, 27.8%, and 45.52% in AZD2281-treated MCF-7, MDA-MB-231 and Hs578t cells respectively. As an initial investigation into the mechanism responsible for AZD2281-mediated radiosensitization, we examined the effect of AZD2281 treatment on the expression of proteins known to be involved in the repair of radiation-induced DSBs. Western blot analysis for Ku70, Ku86, and DNA-PKcs demonstrated a decrease in the levels of all three proteins following AZD2281 treatment in the breast cancer cell lines tested. As an additional test of our hypothesis that AZD2281 impairs the repair of damaged DNA, γ-H2AX foci were assessed as indicators of DNA damage. PARP inhibition markedly enhanced γ-H2AX persistence in the MCF-7 and MDA-MB-231 cell lines suggestive of the presence of persistent DSBs. These data support the use of the PARP inhibitor, AZD2281, in combination with radiation therapy as an innovative treatment strategy to potentially improve outcomes in breast cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5717. doi:1538-7445.AM2012-5717
Abstract 5728: The synergistic effect of Cucurbitacin B and radiation treatment
Authors: Zhang Mei , Yin Liangjie , Yang Shanmin , Hong Jinsheng , Chen Chun , Han Deping , Hou Yanqiang , Zhang Bingrong , Huang Luqiang , Zhang Amy , Vidyasagar Sadasivan , Okunieff Paul , Zhang Lurong 
Published: August 2012

Abstract
Cucurbitacin B (CB), a small molecule purified from Trichosanthes kirilowii Maximowicz, possesses a potent antitumor effect. In this study, we investigated the combined effect of CB and ionizing radiation (IR) on aggressive 4T1 breast cancer cells. In a clonogenic assay, different doses of CB (0, 1.7, or 5 nM) and IR (0, 2, 4, or 6 Gy) were applied to 4T1 cells either in a single regimen or in combination. The surviving fraction at 2 Gy was greatly reduced with the increased doses of CB. The results calculated with CompuSyn program indicated that the combination index (CI) was &lt;1 and the dose reducing index (DRI) was &gt;1, suggesting that the combination of CB and IR has a synergistic effect against cancer cells. Our studies of the underlying mechanism revealed that: 1) CB enhanced IR-induced loss of mitochondria potential, as evidenced by a 10-20% increase in the transition of aggregative JC-1 (representing healthy cells) into monomeric JC-1 (representing early apoptotic cells); 2) cell-cycle analysis revealed that although samples treated with CB or 3 Gy alone had 38% or 29% of cells, respectively, in the G2-M phase as compared to 23% of the vehicle control, the combined treatment encouraged 51% of cells to accumulate in the G2-M phase; and 3) the Western blot assay indicated that survival-related molecules (e.g., phosphorylated Stat 3, c-Myc, Bcl-2, and Bcl-xL) were downregulated, while apoptosis-related molecules (e.g., caspase-9, p21, and p53) were upregulated in the combined treatment group. The data reveal that the systemic administration of CB will not only stop the spread of micrometastases but also enhance local tumor control, which will result in better treatment outcomes. The clinical value of CB should be further explored.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5728. doi:1538-7445.AM2012-5728
Abstract 574: α-santalol induces caspase-dependent apoptosis and G2/M phase cell cycle arrest in human breast cancer cells
Authors: Santha Sreevidya , Bommareddy Ajay , Rule Brittny , Guillermo Ruth , Kaushik Radhey S. , Young Alan , Dwivedi Chandradhar 
Published: August 2012

Abstract
Alpha-santalol, an active component of sandalwood oil, has been shown to have chemopreventive effects on skin cancer both in vitro and in vivo. However, effects of alpha-santalol on other types of cancer have not been studied. In this study, we examine the effects and mechanisms of action of alpha-santalol on human breast cancer cells using estrogen receptor (ER)- positive (MCF-7) and estrogen receptor- negative (MDA-MB-231) breast cancer cell lines. MTT and BrdU cell proliferation ELISA results showed inhibition of cell viability and proliferation in a time and dose-dependent manner in both cell lines. Alpha-santalol at 25-150 µM concentration decreased cell viability after 12h treatment. In addition, TUNEL assay and flow cytometry results revealed that alpha-santalol significantly induced apoptosis in MCF-7 and MDA-MB-231 cells. Further, immunoblotting and caspase activity assays showed involvement of caspase-3, caspase-8 and caspase-9 in apoptotic cell death. Induction of apoptosis by alpha-santalol was further confirmed by detecting the cleavage of Poly (ADP-ribose) Polymerase (PARP) through western blotting. Cell cycle distribution of alpha-santalol treated MFC-7 and MDA-MB-231 cells were analyzed by fluorescence- activated cell sorting (FACS) analysis of propidium iodide staining. We observed that alpha-santalol treatment arrests cell cycle at G2/M phase at 25µM −75µM concentration in both cell lines. Taken together, our studies reveal a potential mechanism for the chemopreventive effect of alpha-santalol on ER- positive and ER- negative breast cancer cells through induction of apoptosis and cell cycle arrest at G2/M phase. Alpha-santalol could be effective for the prevention and treatment of breast cancer. (Supported by Translational Cancer Research Center funded by South Dakota, Governors Office of Economic Development)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 574. doi:1538-7445.AM2012-574
Abstract 5743: Positron emission tomography (PET) imaging analogs of glutamine: Development and evaluation as probes for cancer imaging
Authors: Buck Jason R. , Saleh Sam , Hight Matthew R. , Nickels Mike L. , Manning H. Charles 
Published: August 2012

Abstract
Emerging evidence suggests that nutrient uptake in cancer cells is controlled by oncogenic signaling pathways. The natural amino acid glutamine is an essential nutrient for cell growth and proliferation. Glutamine also participates in protein synthesis and is a nitrogen source for the production of select nucleotides and amino acids. Consequently, quantitative measures of glutamine uptake may reflect critical processes in oncology. Recently, a fluorinated glutamine analog for positron emission tomography (PET) was shown to possess both highly specific cellular uptake in glioma cell lines and in vivo tumor localization (J Am Chem Soc 2011;133:1122-1133). Synthetic methodology leading to this agent, an optically pure 4-fluoro-glutamine derivative, was also reported. Though effective, this convergent synthesis requires multiple steps, extensive chromatographic separation, and nearly a week of reaction time. Employing a chiral auxiliary Schiff base and microwave-assisted organic synthesis, we have significantly improved the synthesis of this and similar agents, drastically reducing the number of synthetic steps (from ten to four) and the overall reaction time (from seven days to two hours). While the radiochemistry relies upon traditional box methods, we are also currently employing high-throughput microfluidic radiolabeling strategies to expedite probe production and labeling efficiency. Finally, using optically pure [18F]4-FGln (2S,4R) synthesized by our improved synthesis, we report preclinical PET images of models of human colorectal cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5743. doi:1538-7445.AM2012-5743
Abstract 577: Equol enhances tamoxifen's antitumor effect by induction of caspase-mediated apoptosis in MCF-7 breast cancer cells
Authors: Charalambous Christiana , Constantinou Andreas I. 
Published: August 2012

Abstract
Soy phytoestrogens, such as daidzein and its metabolite equol, have been proposed to be responsible for the low breast cancer rate in Asian women. However, since these compounds possess both estrogenic and anti-estrogenic properties, it remains unknown whether they provide protection against tumor development and progression. Since the majority of estrogen receptor positive (ER+) breast cancer patients are treated with the selective estrogen receptor modulator tamoxifen, the basic objective of this project is to determine whether equol enhances or inhibits tamoxifen's anti-tumor effect and to identify the molecular mechanisms involved. For this purpose, we examined the individual and combined effects of equol and tamoxifen on the ER+ breast cancer cell line MCF-7 (ERα+/−Rα+). We found that equol at concentrations higher than 10 μM significantly reduced the viability of MCF-7 cells. Furthermore, the combination of equol (100 μM) and 4-hydroxytamoxifen (4-OHT; 10 μM) reduced MCF-7 cell viability and induced apoptosis more effectively than each compound alone. Subsequent treatment of MCF-7 cells with the pan-caspase inhibitor Z-VAD-FMK and the calpain/cathepsin inhibitor ALLN demonstrated that equol and 4-OHT induce apoptosis via both caspase-depended and -independed mechanisms. In order to further investigate the apoptotic pathways employed by equol, 4-OHT and their combination, we evaluated the expression of key proteins involved in apoptosis such as PARP, α-fodrin, AIF, bcl-2, bax, p21 and p53 using Western blot analysis. The combination of 4-OHT and equol induced PARP and α-fodrin cleavage which was inhibited by Z-VAD-FMK indicating that their combination induces caspase-depended apoptosis. This was accompanied by reduced bcl-2:bax ratio confirming a pro-apoptotic effect. The combination of equol and 4-OHT induced caspase-7 cleavage indicating a significant role for caspase-7 in equol- and tamoxifen-induced apoptosis. Finally, upon determination of the effect of equol and tamoxifen on estrogen receptor expression in MCF-7 cells, it was found that equol reduces the ERα:ERα ratio, while 4-OHT increases it. When cells were treated with both compounds we observed that the effect of equol prevailed, providing an additional explanation for the beneficial combined effects of equol and tamoxifen. In conclusion, the effects of equol in potentiating tamoxifen's anti-tumor effect may be explained by the induction of the caspase-mediated apoptotic pathway and the reduction of the ERα:ERα ratio. These results can find applications in clinical or pre-clinical cancer chemoprevention studies against breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 577. doi:1538-7445.AM2012-577