bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5628: Synthetic peptide mimics of LPS: Potential role as novel adjuvants
Authors: Suriano Robert , Shanmugam Arulkumaran , Rajoria Shilpi , George Andrea , Mittelman Abraham , Tiwari Raj K. 
Published: February 2011

Abstract
Lipopolysaccharide (LPS), the principal structural component of gram negative bacterial cell walls, is a potent activator of the immune system responsible for induction of septic shock or systemic inflammation in patients. This systemic inflammation mainly occurs through the interaction between LPS and toll like receptors (TLR-4 and TLR-2) present on antigen presenting cells (APC) thus leading to inflammatory cytokine (TNFα, IL-12, and IL-1β) secretion. Apart from the negative side effects associated with LPS, it mimics an essential and desirable property sought after in developing an optimal adjuvant, namely inducing inflammation and it is this inflammatory property which enables an adjuvant to act as a catalyst in initiating an optimal immune response. Therefore, development and or identification of a compound(s) which can act as an adjuvant by mimicking LPS but lack its harmful systemic side effects is very intriguing. As an initial approach to develop LPS mimics, we used Peptide Phage Display Technology. The peptide library which we used was composed of random linear 7-mer peptides and we identified several peptides which displayed high reactivity with LPS specific antibodies thus suggesting their capability to function as LPS specific peptide mimics. Upon interaction of LPS with TLR-4 and TLR-2 receptors, the one essential event which is at the core of APC activation and initiation of nuclear translocation of nuclear factor kappa B (NFκB). Thus, in order to determine if our peptides functionally mimic LPS, we assessed if they are capable of inducing NFκB nuclear translocation in human embryonic kidney (HEK) cells which are stably transfected to express either TLR-4 or TLR-2. The LPS peptide mimics identified in our study were capable of activating both TLR-4 and TLR-2 thus not only validating the fact that they are LPS peptide mimics but that they are functional LPS mimics and are capable of inducing NFκB nuclear translocation just as efficient as LPS. Identification of LPS peptide mimics opens up a new area in the development of adjuvants which can not only induce localized inflammation but also abrogate the systemic effects of LPS.
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 5628.
Abstract 563: Novel role of VEGF and neuropilin-1 in breast cancer tumor-stromal interactions
Authors: Qu Zhican , Roy Anshu M. , Maxuitenko Yulia Y. , Li Rongbao , Huang Zhi Qiang , Johnson Martin R. 
Published: February 2011

Abstract
Human breast cancers contain high levels of fibroblastic stroma as a critical feature of desmoplasia. The complex interactions between tumor and stromal cells play important roles in tumor growth, metastasis and resistance to anticancer treatments. Our previous in vivo studies showed that increased levels of tumor-released VEGF were associated with increased desmoplastic responses and resulted in a hormonal resistance phenotype of ER+ breast tumor. Based on our findings, a clinical trial conducted at UAB with a new combinational treatment targeting both ER and VEGF signalings has achieved significant objective response in ER+ breast cancer patients. In our current studies, we further studied the role of VEGF in mediating tumor-stromal interactions and initiation of desmoplasia. Our results have shown that tumor released VEGF interacts with stromal fibroblasts which express VEGF receptors R1, R2 and Neuropilin-1 (NRP1), thereby stimulating their infiltration to promote desmoplastic response. Down regulation of NRP1 expression by siRNA significantly abolished the fibroblast chemo-attractive motility towards VEGF, while the VEGFR1 and VEGFR2 blocking antibodies had no effects on their migration mobility, suggesting that NRP1 expressed in fibroblast is involved in tumor-stroma cell interactions in breast cancer. Our studies using breast cancer xenograft mouse model with regulated tumor VEGF expression revealed that tumor VEGF expression was positively correlated with expression of NRP1 and alpha smooth muscle actin (α-SMA, a transformed/myo fibroblast marker) in the tumor stroma. In addition, levels of tumor VEGF, stromal NRP1 and α-SMA were all positively correlated with level of tumor stromal content and tumor growth. Blocking tumor VEGF with a neutralizing antibody (Avastin) as a treatment modality in xenograft mice reversed the VEGF increased desmoplasia. Our study results reveal a novel role of VEGF and NRP1 in tumor-stromal interactions and desmoplasia, indicating NRP1 can be a therapeutic target for breast cancer treatment.
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 563.
Abstract 5631: Nitric oxide-based immune response modifications: A novel paradigm in tumor vaccine development against melanoma
Authors: Olson Samuel Y. , Konishi Tamiko , Bruhn Kevin W. , Craft Noah A. , Garban Hermes J. 
Published: February 2011

Abstract
Although of cardinal importance, the specific role of nitric oxide (NO) in the immune response to cancer remains elusive. NO is generally considered to act as a terminal effector molecule that will promote direct cell death due to its cytotoxic and/or cytostatic properties. Conversely, NO has been also found to be associated with a cytoprotective effect due to its ability to interfere with the apoptotic machinery. We have previously shown that NO is capable to immuno-sensitized tumor cells by regulating the expression of apoptosis-related genes and modifying the structure of many protein targets. Thus, we hypothesize that NO-based modification of an autologous tumor vaccine preparation may improve the immunological priming against tumor cells and potentiate the specific anti-tumor immune response. In order to test this hypothesis we used the well-characterized B16-C57BL/6 syngeneic mouse model of melanoma. B16-F0 melanoma cells were cultured in the presence or absence of a non-cytotoxic concentration of a slow rate release NO donor for 18 hours, and later homogenized into a crude lysate. These preparations were used to vaccinate mice previously challenged with B16-F0 melanoma cells on the contralateral dorsal flank one week before, in order to frame a therapeutic paradigm of treatment in cancer. Additional doses of vaccine were applied every 7 days for a period of 3 weeks and tumor volume was determined every 3 days. Our results demonstrate that the NO-modified autologous cancer vaccine decreases the rate of tumor growth by approximately 85% (p &lt;0.001) by day 25 when compared with the control groups. In addition, this vaccination scheme increases the survival rate by approximately 60% (p &lt;0.001) of the experimental group when compared with controls. NO can exert a myriad of modifications at the genetic, epigenetic and post-translational level in the tumor cells promoting a robust and effective therapeutic immune response against cancer cells. Currently, we are defining the molecular and immunological mechanisms responsible for the significant increase in survival and anti-tumor immune response triggered by the NO-mediated modifications of the melanoma tumor cells. Our results suggest a new role of NO as an immune response modifier that can be exploited in cancer immunotherapy and serves as a model for vaccine development.
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 5631.
Abstract 5632: Mechanism of anemia response by lenalidomide in treating patients with primary myelofibrosis (PMF) and ET-MF is related to suppresion of T regulatory cells (Treg)
Authors: Kafeel Muhammad I. , Sun Yiwu , Chen Chi , Hakimi Neal , Rathnasabapathy Chentyl , Singh Amrit , Lichter Stephen , Wang Jen Chin 
Published: February 2011

Abstract
Except allogenic bone marrow transplantation with either myeloablative or reduced intensity conditioning, there is no effective treatment for PMF. Age-related morbility and mortality factors limit this application. Anti-Jak2 treatment relieves splenomegaly but does not improve cytopenia. IMiDs on the other hand can improve anemia in up-to 20% of transfusion dependent anemic patients with PMF. In order to asses the underlying mechanism and to predict treatment responsiveness, in vitro suppression of Treg cells by lenalidomide correlated to clinical treatment response was performed. Seven patients with transfusion dependent and ESD (erythropoietin stimulating drugs) resistant PMF were studied. Mononuclear cells from blood in patients with PMF were cultured in the culture medium with FCS and Il-2 (100 IU/ml) in the presence of lenalidomide or DMSO for 6 days, the cells were then stained for Treg cells (CD4+, CD 25 +,and FoxP3+,) and analyzed by flow cytometry using Treg Detection Kit from Miltenyi Biotec Inc (Auburn, CA). Treg cells were enumerated as percentage of selected CD4 + cells. The results showed that in the 4 patients who responded to lenalidomide treatment, Treg cells were suppressed by the in vitro testing by lenalidomide, while in the three patients who were clinically refractory to lenalidomide treatment, their Treg cells were not suppressed by in vitro lenalidomide treatment. These results suggest that in transfusion dependent PMF, Treg cells may play a role in the pathogenesis of anemia and that effectiveness of lenalidomide treatment may be partly related to its suppression of Treg cells. Further studies to recruit more patients and to explore the role of Treg cells in modulating erythroipoiesis in PMF using the erythroid methylcellulose culture systems are currently in progress.
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 5632.
Abstract 5634: Chemical antibodies for cancer immunotherapy
Authors: Evbuomwan Moses O. , Maeda Yoshiko , Kumaresan Pappanaicken , Lam Kit S. 
Published: February 2011

Abstract
The absence of curative therapies for recurrent forms of metastatic cancer has prompted a vigorous search for novel treatment strategies. Cancer immunotherapy uses the host immune system, either directly or indirectly, to combat cancer. The more successful cancer immunotherapies are antibody-based. In this study we hypothesized that a chemical antibody (chembody) with an intact Fc region can be constructed by conjugating tumor cell specific peptidomimetic agents (ligands) to the Fab region of human IgG (hIgG). The ligand of interest, RGD, binds effectively to αVβ3 integrin expressed on tumor cells. The resultant chembody will have the ability to opsonize the tumor cells and elicit host immune response against cancer cells by recruiting the immune effector cells. In this study, we (1) conjugate naïve hIgG with the ligand, (2) verify ligand conjugation, and (3) test the efficacy of the chembody. The 2-iminothiolane conjugation method was employed to conjugate the ligand to naïve hIgG. The conjugation was verified by performing Western blot analysis, MALDI-MS assay, and cell binding assay. The Western blot and Coomassie blue staining showed that conjugation was successful while the MALDI-MS assay showed a 1:3 conjugation ratio. Colorimetric cytotoxicity assay will be used to test the efficacy of the chembody. We expect chembodies with intact Fc region to be tumor specific, and actively recruit immune cells to the tumor site and have low immunogenicity. This novel individualized medicine approach in cancer immunotherapy can be very effective in eliminating the remaining cells responsible for relapse after chemotherapy or radiotherapy.
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 5634.
Abstract 5643: Enhancement of tumor radiosensitivity by sorafenib
Authors: Kim Yong Bae , Jeung Hei Cheul , Rha Sun Young , Chung Hyun Cheol , Kim Gwi Eon , Cho Nam Hoon 
Published: February 2011

Abstract
Purpose: Sorafenib, an orally available multikinase inhibitor, is approved by the U.S. Food and Drug Administration for the treatment of patients with advanced renal cell carcinoma and those with unresectable hepatocellular carcinoma. However, there has been no data about synergistic interaction between sorafenib and radiation. In this study, we investigated the possible sorefenib-induced enhancement of radiosensitivity.
Experimental Design: The effects of sorafenib on the in vitro radiosensitivity of DLD-1 and HT-29 (colon cancer) cell lines were evaluated using clonogenic assay. The impact of sorafenib on radiation-induced cell cycle kinetics and on apoptosis was analyzed using flow cytometry evaluated via propidium iodide and annexin V. ERK signaling were examined by Western blot analysis. DNA damage and repair were evaluated using phosphorylated histone H2AX (γH2AX). Tumor growth delay was used to evaluate the effects of sorafenib on in vivo (DLD-1) tumor radiosensitivity.
Results: Exposure of each cell line to sorafenib combined with irradiation resulted in an increase in radiosensitivity with dose enhancement factors at a surviving fraction of 0.25 ranging from 1.21 to 1.61. Sorafenib and radiation induced accumulation of tumor cells in G2-M phase, but had no effect on radiation-induced apoptosis. As a measure of DNA double strand breaks, γH2AX foci were determined as a function of time after irradiation + sorafenib combination. Irradiated-alone cells showed more rapid reduction of γH2AX foci than irradiation + sorafenib combination cells. Tumor xenograft studies confirm that administration of sorafenib results in profound tumor growth inhibition when combined with radiation.
Conclusions: These results indicate that sorafenib can enhance tumor cell radiosensitivity in vitro and in vivo and suggest that this effect involves G2-M phase arrest and an inhibition of DNA repair.
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 5643.
Abstract 5645: Growth inhibitory activity of ethanol extracts of Chinese and Brazilian propolis in human colon carcinoma cell lines
Authors: Yoshida Ichiro , Nakashima Makoto , Ishihara Masashi , Morioka Takamitsu , Itoh Yoshinori , Yoshimi Naoki , Suzui Masumi 
Published: February 2011

Abstract
Propolis is a natural product derived from plant resins collected by honeybees, and has been used globally as a folk medicine for centuries. More than 300 bio-active compounds have been identified from bee propolis. In the current study, we examined whether the ethanol extracts of Chinese and Brazilian propolis exert anticancer activities in four human colon carcinoma cell lines, CaCo2, HCT116, HT29 and SW480. Propolis samples were extracted with ethanol, and the crude extracts were dissolved in dimethylsulfoxide and used for the following experiments. We also examined the effects of the ethanol extract of Chinese propolis on cell proliferation, cell cycle progression, apoptosis, and the levels of expression of cell cycle control molecules in the HCT116 and HT29 cell lines. In the HCT116, HT29 and SW480 cell lines, the extracts of both Chinese and Brazilian propolis caused a marked dose-dependent growth inhibition, with IC50 values in the range of 4-41 μg/ml. In the FHC normal human colonic epithelial cell line, the extract of Chinese propolis failed to cause a marked growth inhibition, the growth inhibition rate was about 20%, whereas it was about 90% in the HCT116 and HT29 cell lines. In the HCT116 cell line, at concentrations of 10 and 20 μg/ml the extract of Chinese propolis caused a marked increase in sub-G1 fraction of cells in a dose-dependent fashion. The propolis extract (20 μg/ml) caused a significant increase of cells in sub-G1 and this increase was associated with a concomitant relative decrease of cells in the G1, S and G2-M phases of the cell cycle, indicating that Chinese propolis extract induced apoptosis in the HCT116 cell line. In addition, Chinese propolis extract caused a dose-dependent increase in the cellular mRNA levels of p21CIP1 and p53 in the HCT116 cell line. These findings indicate that the ethanol extracts of propolis contain components that may have anticancer activity. Thus, propolis and related products may provide a novel approach to the chemoprevention and/or chemotherapy of human colon carcinoma.
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 5645.
Abstract 5646: Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion and angiogenesis of SW480 human colon cancer cells by modulating Wnt/b-catenin signaling
Authors: Song Kyoung-Sub , Li Ge , Kim Tae-Dong , Kim Jong-Seok , Shin So-Yeon , Jing Kaipeng , Park Jong-Il , Kweon Gi-Ryang , Hwang Byung-Doo , Yoon Wan-Hee , Lim Kyu 
Published: February 2011

Abstract
It is known that polysaccharide extracted from Phellinus linteus (PL) mushroom possess antitumor activity. We previously have demonstrated that PL has direct antitumor effect through apoptosis and G2/M cell cycle blockade in SW480 human colon cancer cells. However, the molecular mechanisms responsible for antitumor and antiinvasive behavior of PL remain to be explored.
Employing SW480 colon cancer cells which are overexpressed B-catenin, we demonstratd that PL significantly inhibited cellular proliferation and remarkable decrease of B-catenin expression on Western blot and indirect immunofluorescence detection in PL treated cells. Cyclin D1, one of the B-catenin controlled downstream genes and TCF/LEF transcription activity were also significantly reduced when PL was treated. PL inhibited in vitro invasion and motility of SW480 cells and the activity of matrix metalloproteinase (MMP)-9 on zymography. In addition, PL inhibited human umbilical vein endothelial cell (HUVEC) proliferation and capillary tube formation. Tumor growth of SW480 cells implanted into nude mice were significantly inhibited with PL treatment in a dose-dependent manner. Immunohistochemical analysis of xenografted tumor tissue showed that apoptotic index was markedly increased and nuclear staining of b-catenin was decreased. However, the proliferation index and microvessel density were significantly decreased. These data demonstrate that PL downregulates Wnt/b-catenin signaling pathway and inhibits multiple steps in tumor invasion in certain colon cancer cells.
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 5646.
Abstract 5655: 3,3′-Diindolylmethane selectively induces proteasomal degradation of the class I histone deacetylases
Authors: Li Yongming , Li Xia , Guo Bin 
Published: February 2011

Abstract
This study aims to identify the molecular target of 3,3′-Diindolylmethane (DIM), an anti-cancer agent that induces cell cycle arrest and apoptosis through unknown mechanisms. Previously, we have shown that DIM can enhance the efficacy of butyrate in colon cancer prevention in the APCmin/+ mouse model [Cancer Prevention Research, 2(6):581-9, 2009]. In our studies trying to identify the intracellular target of DIM, we found that DIM selectively induced proteasome-mediated degradation of the class I histone deacetylases (HDAC1, HDAC2, HDAC3, and HDAC8) in colon cancer cells, without affecting other HDAC proteins (class II or class III HDACs). DIM-induced down-regulation of the class I HDACs was also observed in vivo in tumor xenografts in nude mice. The depletion of the HDACs by DIM caused a reduction of the HDAC activity on the promoters of CDKN1A/WAF1/CIP1 and CDKN1B/KIP1 genes (encoding cyclin-dependent kinase inhibitors p21 and p27, respectively) and significantly increased the expression of p21 and p27, which arrested cells at the G2 phase of the cell cycle. The degradation of the HDACs also caused DNA damage and triggered apoptosis. Based on these data, we conclude that DIM acts by selectively targeting the class I HDACs to promote their degradation.
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 5655.