bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5578: Quantitative kinase inhibitor profiling in native cell and tissue extracts
Authors: Patricelli Matthew P. , Nomanbhoy Tyzoon K. , Kozarich John W. , Gray Nathanael S. , Zhang Jianming , Wu Jiangyue 
Published: February 2011

Abstract
Protein kinases are currently the subject of intense pharmaceutical industry attention. An array of assays and tools have been developed to study their biological and structural properties, however despite these efforts, many questions remain regarding the nature and functional consequences of kinase regulatory events in vivo. We previously detailed a probe-based method for comprehensively probing the ATP binding sites of native protein kinases directly in cell or tissue lysates. Here we report several advances that dramatically increase the sensitivity, quantitative accuracy, and efficiency of this method. Using these improved methods, we determined the Kd values of ATP, Staurosporine and several clinically relevant kinase inhibitors against more than 200 protein and lipid kinases in two cell lines (HL60 and PC3). While the data supports many general trends and confirmed targets of the inhibitors identified through recombinant kinase assays, several striking differences were found. Detailed investigation of these differences reveal that native kinases can exhibit dramatically different behavior when compared to their recombinant counterparts. Overall these data provide an unprecedented picture of native kinase behavior and have profound implications for the development of kinase inhibitors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5578.
Abstract 5582: NY-ESO-1-specific T-cells in melanoma patients with good clinical outcome after vaccination using mRNA as the immunogen
Authors: Zelba Henning , Weide Benjamin , Garbe Claus , Pawelec Graham P. , Derhovanessian Evelyna 
Published: February 2011

Abstract
Although success in active cancer immunotherapy is often disappointing, vaccination against cancer- associated antigens has become an important tool in cancer management, resulting in an increasing list of possible antigen targets. However, previous studies have shown that vaccination against certain antigens results in a better clinical outcome than others. This indicates the importance of immune monitoring by helping to choose the antigens with the highest potential for success.
In order to address this issue, we have analysed CD4+ and CD8+ T-cell responses against four common melanoma-associated antigens, namely NY-ESO-1, Melan-A, MAGE-A3 and Survivin, in melanoma patients undergoing immunotherapy. Blood samples from 5 long-term survivors after treatment with anti-CTLA-4 antibody as well as 12 patients vaccinated with mRNA encoding these four antigens were tested in this study. Antigen-specific T-cell responses were detected using peptide mixtures spanning the whole sequence of the antigen after one round of in vitro sensitization. Intracellular production of six different cytokines (IFN-γ, TNF, IL-2, IL-4, IL-10 and IL-17) was measured in CD4+ and CD8+ T-cells by 14 colour multiparameter flow cytometry, allowing simultaneous analysis of the phenotype and effector functions (TH1, TH2, TH17) on a single-cell basis.
NY-ESO-1-specific CD4+ and/or CD8+ T-cell responses were detected in 4/5 long-term (up to 3 years and continuing) survivors receiving anti-CTLA-4 treatment, whereas responses against the remaining three antigens were either absent or present at lower frequencies. In the mRNA vaccination trial, NY-ESO-1-specific responses were detected in the only stage IV patient with &gt;25% shrinkage in the size of the metastasis and two stage IV patients, who have remained tumor-free for 21 and 12 months since start of the vaccination. NY-ESO-1-specific immune responses were present in only 1/9 patients who progressed or died during this period. In all 6 patients with clinical benefit, the NY-ESO-1-specific T-cells produced high levels of IFNγ and TNF.
Our data suggest that NY-ESO-1 might be a promising target antigen in melanoma patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5582.
Abstract 5585: Optimal conditions for dendritic cells labeling with superparamagnetic iron oxide for cellular magnetic resonance imaging
Authors: Kobayashi Yasunobu , Shimizu Koichi , Okuyama Ryuji , Imai Kenichiro , Ohno Satoshi , Ostapenko Valentina V. , Kobayashi Tamiyo , Aruga Atushi , Tanigawa Keishi 
Published: February 2011

Abstract
Non-invasive cell-tracking in vivo could be an invaluable tool in cell-based therapy, which determines whether or not administrated cells effectively reach their target sites. Recent reports have shown that magnetic resonance imaging (MRI) is a useful and feasible tool to detect in vivo migration and biodistribution of magnetically labeled cells. In this study, we examined optimal conditions for labeling monocyte-derived dendritic cells (Mo-DCs) with a MR contrast agent (Resovist®) consisting of superparamagnetic iron oxide (SPIO) particles. We found that simple addition of Resovist® in the culture medium makes it possible to label Mo-DCs sufficiently and efficiently, and SPIO-uptake appeared to be saturated by its 100μg/ml treatment. FCM analysis showed that expression levels of CD80, CD86, CCR7, HLA-A,B,C and HLA-DR in SPIO-labeling Mo-DCs (100μg/ml Resovist®-treated) were similar to those in non-labeling cells. In vitro migration assays revealed that there were no significant differences between labeling and non-labeling cells in both chemotactic activities to CCL19 and random migration capacities on fibronectin-coated plates. In addition, IFNγ-ELISPOT assay showed labeling and non-labeling Mo-DCs were able to stimulate antigen-specific T cells to a similar extent, indicating that Resovist®-treatment did not affect the capacities of Mo-DCs to take up, process and present antigens to T cells. Taken together, we concluded that labeling of Mo-DCs with SPIO, particularly with 100μg/ml Resovist® could be a potent method for monitoring trafficking and biodistribution of these cells in clinical studies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5585.
Abstract 5595: Antitumor immune responses to Nitroreductase/CB1954 and 4-1BBL gene therapy
Authors: Salman Asmaa M. , Searle Peter F. 
Published: February 2011

Abstract
Gene-directed enzyme prodrug therapy using the non-mammalian nitroreductase enzyme (NTR) and CB1954 prodrug is a promising approach for local management of cancer through targeted chemotherapy. Whilst there is some evidence that tumor cell killing via NTR/CB1954 may also induce a systemic, immune bystander effect, this needs further investigation. To address this, a transgenic adenocarcinoma of the mouse prostate tumor cell line stably expressing cytoplasmic ovalbumin (TRAMPOva) was transduced with retroviruses encoding either the therapeutic NTR or 4-1BBL gene. The generated sub-clones were used to establish subcutaneous tumor in syngeneic mice. Adoptive transfer of Ova-specific transgenic (OT-1) T cells facilitates tracking of the specific anti-tumor immune response to the gene therapy in vivo. By examining the effect of NTR/CB1954 mediated cytotoxicity on the generation of effector memory T cells, we find that treatment of Ova+NTR+ tumor bearing mice with prodrug induced significant tumor regression. This was associated with enhanced CD8+ T cell maturation and cytolytic activity. However, adoptive transfer of 1×105 of these Ova-specific memory cells did not provide prophylactic protection to immunodeficient mice against TRAMPOva tumor challenge. Therefore, we attempted to enhance the immunogenicity of tumors by delivering the 4-1BBL costimulatory ligand gene to tumor cells. We demonstrate that immunocompetent mice receiving TRAMPOva+4-1BBL cells resisted tumor formation in a 120 day follow-up period, while those receiving TRAMPOva cells developed progressive tumors at earlier time points. Tumor rejection was accompanied by generation of higher frequencies of Ova-specific CD8+ memory T cells that showed effector cytolytic function following challenge with splenocytes loaded with Ova peptide in vivo. Overall, our results show that either NTR/CB1954-mediated cell death, or tumor expression of 4-1BBL can induce a tumor-specific CD8+ T cell response. Combining these approaches may offer a strategy to provide long-lasting anti-tumor immunity in vivo.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5595.
Abstract 5596: Enhanced anti-tumor effect of combination therapy with anti-CD40 antibody and the mTOR kinase inhibitor AZD8055
Authors: Jiang Qun , Weiss Jonathan M. , Ortaldo John R. , Back Timothy , Guichard Sylvie , Thakurta Anjan , Wiltrout Robert H. 
Published: February 2011

Abstract
mTOR signaling, which plays a central role in controlling cell cell proliferation, survival, mobility and angiogenesis, is considered an important target for new anticancer drugs development. The involvement of the CD40/CD154 signaling pathway has also been reported to play an important role in regulating anti-tumor immune responses. In this study, using a first-in-class orally bioavailable mTOR kinase inhibitor, AZD8055, which, unlike rapamycin, can inhibit both mTORC1 and mTORC2, we evaluated the anti-tumor efficacy of mTOR kinase inhibitor treatment alone in a murine model of metastatic renal cell carcinoma (Renca) and compared biological responses achieved by administering AZD8055 as a single agent to those obtained in combination with agonistic anti-CD40 antibody. In vitro survival assays showed that Renca cell apoptosis could be induced by AZD8055. In vivo, although both agents administered alone had some anti-tumor efficacy, the combination of AZD8055 and CD40 Ab induced a significant anti-tumor response in both intra-renal and intra-splenic inoculations model of renal cell carcinoma, as compared to single agent treatments. The combination treatment, also resulted in an increase and activation of tumor- and liver-associated macrophages, NK cells and CD8 T cells in vivo. AZD8055/anti-CD40 treatment also increased the level of systemic Th1 cytokines, including IL-12, IFN-γ, TNFα. IFN-γ production by CD8+ T cells and TNFα production by macrophages were also found to be elevated in the AZD8055/anti-CD40 combination treated-group, compared with any single treatment group. Furthermore, the expression of Th1-associated chemokines, RANTES and IP10, were significantly induced in the combination treated-group. These data suggest that the combination of mTOR kinase targeting agents with immunotherapy could be an area of further development in renal cancer therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5596.
Abstract 5649: Highly synergistic anti-tumor efficacy induced by the combination of two natural dietary agents, luteolin and EGCG: Role of p53 phosphorylation, stabilization and translocation
Authors: Amin A.R.M. Ruhul , Wang Dongsheng , Zhang Hongzheng , Peng Shifang , Koenig Lydia , Brandes Johann C. , Mourad Tighiouart , Khuri Fadlo R. , Chen Zhuo G. , Shin Dong M. 
Published: February 2011

Abstract
Natural dietary agents have drawn a great deal of attention for cancer prevention and therapy because of their wide safety margin and easy availability. However, single agent intervention has failed to bring the expected outcome in clinical trials in many instances; therefore, combinations of chemopreventive agents are gaining increasing attention. In the present study, we have investigated a combinatorial approach using two natural dietary polyphenols, luteolin and EGCG, and found that combination of the two compounds at low doses (at which almost no apoptosis was observed after single agent treatment) tremendously increased apoptosis (50-70%) in both head and neck and lung cancer cell lines (a panel of 11 cell lines tested). This combination also significantly inhibited growth of head and neck cancer Tu212 and lung cancer A549 xenografts as compared with either of the single agents (P value &lt; 0.05). Ki-67 and TUNEL staining of the xenografted tumor tissues also showed statistically significant decrease in the number of Ki-67 and increase in TUNEL positive cells after combined treatment with luteolin and EGCG as compared with single agent treatment or untreated control. Further mechanistic study showed that the combination-induced both mitochondria-dependent and -independent apoptosis varying among cell lines. Although the combination was effective against cell lines regardless of their p53 status, those with wild-type p53 were much more sensitive to the treatment than those with mutant or no p53. Ablation of p53 using shRNA strongly inhibited apoptosis (&gt;50%) as evidenced by decreased PARP and caspase 3 cleavage. Moreover, we found more efficient stabilization and phosphorylation of p53 at Ser15 by the combination as compared with either single agent, particularly when the basal p53 levels were low. In addition, we observed mitochondrial translocation of p53 after treatment with luteolin or the combination of EGCG and luteolin. Taken together, our results, for the first time, suggest that combination of luteolin and EGCG has synergistic/additive growth inhibitory effects both in vitro and in vivo via a p53-dependent pathway and will provide an important rationale for chemoprevention or treatment trials using this combination. This research was supported by the National Cancer Institute award 5 P50 CA128613 SPORE in Head and Neck Cancer (ARA, JCB, TM, FRK, ZGC and DMS).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5649.
Abstract 5653: The in vitro effects of aloe-emodin on head and neck squamous cell carcinoma
Authors: Chaisuparat Risa , Scheper Mark A. , Thunyakitpisal Pasutha 
Published: February 2011

Abstract
Aloe emodin (AE) is an anthraquinone compound extracted from the leaves of aloe vera plants, which has been shown to have anti-neoplastic activities on various cancers. This study investigated the effects of AE on cell proliferation and apoptosis induction in head and neck squamous cell carcinoma (HNSCC) using a HEP-2 cell line model. HEP-2 cells were either left untreated, normal media, (Control) or treated with different concentrations of AE (6.25-100 µM) for 24 h. Cell proliferation was evaluated using MTS and crystal violet staining assays. Cell cycle was analysed using flow cytometry measuring DNA content (Propidum Iodide). Apoptosis was analysed by TUNEL and apoptotic gene expression was measured by human apoptosis RT2 Profilertm polymerase chain reaction array. Cell proliferation assays showed that AE inhibited cell proliferation in a dose dependent manner. MTS assay demonstrated a 26.96% and 43.12% decrease in cell proliferation at 6.25 and 12.5 µM, respectively. In confirmation of the MTS assay, crystal violet staining displayed 35.58% and 39.42% reduction in cell proliferation at 6.25 and 12.5 µM, respectively. Further, AE treatment demonstrated an increase in G1 cell cycle arrest compared to the control. Apoptosis analysis exhibited an increase in early and late stage apoptotic cells in the AE treated group. TUNEL assay demonstrated a 2 to 3 fold increase in apoptosis compared to the control. Finally, the apoptotic gene expression array revealed differential expression among the 12.5 µM AE treated cells and control cells of several genes involved in apoptosis including: TNF, BCL2, caspase and death domain gene families. In conclusion, we present original data for the first time showing AE is capable of producing anti-neoplastic effects, inhibiting cell proliferation and inducing apoptosis, in HNSCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5653.
Abstract 5672: A novel anti-cancer effect of hesperidin: reversion of epithelial mesenchymal transition in human prostate cancer cells
Authors: Lau Yiu-Keung 
Published: February 2011

Abstract
Prostate cancer is the most common noncutaneous malignancy in men. About one third of prostate cancers invade surrounding tissues, and metastasize to distant organs at the time of diagnosis. Once prostate cancer metastasizes to distant organs, the disease is basically not curable. The median survival for men with metastatic prostate cancer is 1 to 3 years. Epithelial mesenchymal transition (EMT) is a process facilitating cancer cell invasion and metastasis. Hesperidin (3′-5,7-trihydroxy-4′-methoxyflavanone 7-rhamnoglucoside) is a flavonoid found abundantly in citrus fruits. It demonstrates anti-inflammatory, anti-oxidative, and anti-proliferative actions in various cancer types. Its effect on EMT of prostate cancer is not known. We therefore hypothesize that hesperidin inhibits the cell growth and EMT of prostate cancer cells. In our study, we use androgen-sensitive prostate cancer LNCaP cells, androgen-insensitive Du 145 and PC3 cells, and benign prostate BPH-1 cells. These cell lines are treated with increasing concentrations of hesperidin, from 10 µM to 200 µM. We first examine the effects of hesperidin on cell viability by MTT assays. Hesperidin inhibits all three prostate cancer cell viability in a dose dependent manner but it has no significant effects on that of normal prostate cells, BPH-1. We then examine whether hesperidin reverses EMT in these cells by investigating the migration ability and the expression of EMT marker. Hesperidin at 100 µM and 200 µM inhibits the cell migration ability of PC3 and LNCaP as showed by wound scratch assay. Next, we examine expression of E-cadherin, a molecular marker for EMT, by immunohistochemistry. Hesperidin at 100 µM significantly enhances the membranous expression of E-cadherin in LNCaP cells after 48 hours of treatment as compared to the control. There are no significant changes in androgen receptor (AR) protein level or PSA mRNA after hesperidin treatment suggestive that the effects of hesperidin on LNCaP cells are AR-independent. In conclusions, our data provide novel findings that hesperidin can induce the reversion of EMT in prostate cancer cells. Hesperidin may therefore be a potential chemopreventive agent in human prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5672.
Abstract 569: Dicycloplatin, a platinum compound appears effective in treating prostate cancer
Authors: Yang Xuqing , Guo Yi , Mueller Michael D. , Yu Jing Jie 
Published: February 2011

Abstract
Dicycloplatin (DCP) is a new platinum-based drug developed in China. Due to its special structure, DCP possesses superior stability and water-solubility, compared to cisplatin and carboplatin. Experimental findings in China demonstrate low in vitro cytotoxicity of dicycloplatin against a variety of human cancer cell lines. DCP toxicity profile of 210 mg/kg of LD50 compares favorably to 14.27 mg/kg for cisplatin and 164 mg/kg for carboplatin. In vivo studies indicate that IV administration of 20 mg/kg DCP in rats is followed by 3.64 μg/g of drug distribution in the prostate. Histoculture Drug Response Assay (HDRA) confirms clinical efficacy of chemotherapy for various cancer types, including prostate cancer. Pre-clinical and clinical studies in China suggest that DCP produces fewer side effects with a maximum tolerated dose of 650 mg/m2. Patients with prostate cancer treated by DCP alone demonstrated persistent benefits. In one case, the prostate-specific antigen (PSA) level returned to normal after 5 consecutive dosages of 600mg administered orally every two weeks. No significant side effects were observed. Investigations of molecular mechanisms at WVU, USA suggest that DCP induces gene signature profile in human ovarian cancer cells through mechanisms similar to other platinum drugs. In conclusion, dicycloplatin may be an effective chemotherapeutic agent for patients with prostate cancer and further investigations in animal and preclinical tests are warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 569.