bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-318: Development of Listeria monocytogenes-based vaccine that concomitantly targets both the tumor cells as well as tumor vasculature
Authors: Wallecha Anu , Rivera Sandra 
Published: February 2011

Abstract
Recently we described the development of Listeria monocytogenes (Lm) based chimeric human Her2/neu gene (ChHer2) harboring most of the known MHC class I epitopes of the HER2/neu oncogene (ChHer2) when expressed as a fusion protein to a non-hemolytic fragment of listeriolysin O. This construct when tested for immunogenicity and anti-tumor effects in mice proved to be efficacious in breaking immune tolerance toward the HER2/neu self-antigen and elicited strong T cell immune responses in experimental animals. These results support the further clinical development of this vaccine for treatment of HER2/neu overexpressing malignancies such as breast, colorectal and pancreatic cancers. Preclinical studies with three different Lm based vaccines targeting angiogenesis antigens have demonstrated potential in mediating the regression of tumors arising from distinct origin such as breast or skin cancer. Therefore, we hypothesized that the delivery of an angiogenic antigen simultaneously with a tumor-associated antigen will likely have a synergistic effect by impacting on tumor growth via targeting blood vessels while at the same time targeting a tumor specific antigen to enhance effector T cell infiltration in the tumor and improve the vaccine therapeutic efficacy. If true, this will result in a flexible platform by using different tumor antigens. We have created two dual recombinants Lm vaccines that express and secrete both the tumor specific antigen such as ChHer2 and tumor vasculature antigen such as High molecular weight melanoma associated antigen (HMW-MAA) successfully. Currently we are evaluating the anti-tumor effects and immune responses generated by these constructs. If successful, this study will have a great potential for human use in cancer immunotherapy.
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 LB-318.
Abstract LB-324: A toll-like receptor 4 agonist enhances the efficacy of trastuzumab therapy and promotes adaptive immunity and long-term protection against a human ErbB-2 (HER2)-transfected syngeneic tumor in a human HER2 transgenic mouse model
Authors: Wang Shangzi , Xu Wei , Tang Yong , Surana Rishi , Bingham Catherine , Astsaturov Igor A. , McCarthy Kenneth , Alpaugh R. Katherine , Littlefield Bruce A. , Hawkins Lynn D. , Ishizaka Sally T. , Weiner Louis M. 
Published: February 2011

Abstract
Antibodies against cancer-relevant targets can recruit Fc receptor-bearing myeloid and natural killer cells to mediate antibody dependent cellular cytotoxicity (ADCC). Toll-like receptors are potent activators of the innate immune system and generate signals leading to the initiation of an adaptive immune response that can be utilized for therapeutic purposes. We tested the efficacy of E6020, a TLR4 agonist, administered in combination with the clinically approved anti-HER2 antibody trastuzumab. A four-week course of therapy with trastuzumab and E6020 protected against the outgrowth of syngeneic D5 melanoma cells transfected with the human tumor antigen HER2 in immunodeficient C57BL/6 SCID mice, in immunocompetent wild-type C57BL/6 mice as well as in human HER2-tolerant C57BL/6 hmHER2 transgenic mice. In each tested strain of mice, the addition of E6020 to trastuzumab significantly increased the proportion of animals that survived initial tumor challenge compared to trastuzumab treatment alone (83% vs. 33% in C57BL/6 hmHER2 transgenic mice; p &lt; 0.05). To determine if apparently cured mice had been effectively immunized against human HER2, the transgenic mice were inoculated subcutaneously with 103 D5-HER2 cells and then received a 4-week course of trastuzumab+E6020, or trastuzumab alone. Animals that survived the primary tumor challenge were followed for at least 120 days and then rechallenged with 5 × 103 D5-HER2 or unmodified D5 cells and followed for a minimum of 60 additional days. Mice that had been initially treated with the combination of trastuzumab and E6020 demonstrated superior protection (22/30; 73%) to those treated with trastuzumab alone (16/36; 44%; p &lt; 0.05) against rechallenge with D5-HER2, but no protection was seen against D5 challenge. Both CD4 and CD8 T-cells were required for full protection against rechallenge. These findings suggest that trastuzumab therapy can induce a host-protective adaptive immune response. Moreover, combined treatment with trastuzumab and a TLR4 agonist enhances both the direct anti-tumor effects of trastuzumab and a host-protective human HER2-directed adaptive immune response.
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 LB-324.
Abstract LB-330: Endogenous T cell responses to lung adenocarcinoma neoantigens delay malignant tumor progression
Authors: DuPage Michel , Cheung Ann F. , Mazumdar Claire , Winslow Monte M. , Bronson Roderick T. , Crowley Denise , Jacks Tyler 
Published: February 2011

Abstract
Neoantigens derived from somatic mutations in tumors may provide a critical link between the adaptive immune system and cancer. However, it has been difficult to properly recapitulate immune responses against tumor neoantigens in models of the human disease. Here we describe a novel system to induce the expression of potent neoantigens in a genetically engineered mouse model of lung cancer. We show that endogenous T cells respond to and infiltrate tumors, resulting in a significant delay in malignant progression. However, despite continued neoantigen expression, T cell infiltration does not persist and tumors ultimately escape immune attack. In contrast, transplantation of cell lines derived from lung tumors that express neoantigens, even those that have escaped the immune system in their autochthonous setting, or prophylactic vaccination against autochthonous tumors, evoke robust T cell responses that either lead to rapid tumor eradication or selection of tumors that lose neoantigen expression. These results support clinical data that suggest a role for the immune system in cancer suppression rather than prevention. This model provides a valuable system for the optimization of immune therapies that can eradicate human cancers.
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 LB-330.
Abstract LB-334: IFN-γ and TRAIL cooperate to enhance colon carcinoma apoptosis and immune cell-mediated anti-tumor cytotoxicity
Authors: Liu Feiyan , Liu Kebin 
Published: February 2011

Abstract
Development of cancer-selective therapy with little or no toxicity is one of the goals of modern translation cancer research. TRAIL selectively induces apoptosis in various types of tumor cells but not in normal cells, and thereby is a promising selective anti-cancer agent. Currently, TRAIL is in early stage clinical trials for treatment of almost all types of human cancers. However, tumor cell resistance to TRAIL is a major impediment of TRAIL therapy. Most current approach to overcome TRAIL resistance is by pharmacologic means, which often involve use of toxic therapeutic agents. In this study, we demonstrated here that IFN-γ, a cytokine secreted by activated immune cells, modulate the mitochondrion apoptosis pathway to sensitize human colon carcinoma cells to TRAIL-induced apoptosis. IFN-γR is expressed in human colon carcinoma, and moderate to high positive correlations were found between cell surface IFN-γR level and TRAIL-induced apoptosis. Furthermore, activated CD8+ T cells express high levels of IFN-γ and TRAIL, and TRAIL is also expressed in tumor-infiltrating CD4+, CD8+ T cells, macrophage and NK cells. Consequently, blocking TRAIL function significantly increased colon carcinoma metastasis in vivo. Our data suggest that cooperation between IFN-γ and TRAIL play critical role in anti-tumor immunity.
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 LB-334.
Abstract LB-34: Targeted delivery of siRNAs to diverse solid cancers by a novel immunoconjugate comprising tetrameric human protamine linked to an internalizing anti-TROP-2 humanized antibody
Authors: Gupta Pankaj , Goldenberg David M. , Chang Chien-Hsing 
Published: February 2011

Abstract
Despite the potential of RNA interference (RNAi) to silence specific genes, the full therapeutic potential of RNAi remains to be realized due to the lack of an effective delivery system to target cells in vivo. To address this critical need and prompted by the promising results obtained with fusion proteins comprising the nucleic-acid-binding human protamine and a cell-targeting Fab or scFv, we have developed novel immunoconjugates having multiple copies of human protamine tethered to a tumor-targeting, internalizing antibody for targeted delivery of siRNAs in vivo. The Dock-and-Lock (DNL) method developed by us provides the design and strategy for building such multifunctional agents. DNL enables site-specific, self-assembly of two modular components with each other, resulting in a stable covalent structure of defined composition with retained bioactivity. The basic strategy of DNL involves the generation of two types of modules, one containing the dimerization and docking domain (DDD) of cAMP-dependent protein kinase (PKA) and the other containing the anchoring domain (AD) of a related A-kinase anchoring protein (AKAP). Docking a DDD-containing module with an AD-containing module occurs spontaneously, and the resulting complex is locked with disulfide bonds to enhance in vivo stability. We generated DDD2-L-thP1, a DDD-module of truncated human protamine (thP1, residues 8 to 29 of full human protamine 1), in which the sequences of DDD2 and thP1 are fused to the light chain of a humanized antibody at the N- and C-termini, respectively. The reaction of DDD2-L-thP1 under mild redox conditions with hRS7-IgG-AD2, an AD-module derived from an anti-TROP-2, internalizing, humanized antibody, resulted in the facile formation of the desirable DNL complex, designated E1-L-thP1, which contains four copies of thP1 appended to the carboxyl termini of the heavy chains. The purity and molecular integrity of E1-L-thP1 following Protein A purification was shown by size-exclusion HPLC and SDS-PAGE. In addition, the ability of E1-L-thP1 to bind plasmid DNA or siRNAs was demonstrated by the gel shift assay. E1-L-thP1 was effective in protecting the bound DNA from digestion by nucleases added to the sample or present in serum, and its function to carry siRNAs into TROP-2 expressing cancer cells was confirmed by fluorescence microscopy using FITC-conjugated siRNAs and the human lung cancer cell line, Calu-3. Further evaluation of the in vitro and in vivo efficacy of E1-L-thP1 for delivery of CD74-specific siRNAs to treat TROP-2 expressing pancreatic cancer is ongoing.
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 LB-34.
Abstract LB-354: Dysregulation of microRNA-34a expression in head and neck squamous cell carcinoma promotes tumor growth and tumor angiogenesis
Authors: Kumar Bhavna , Yadav Arti , Teknos Theodoros N. , Kumar Pawan 
Published: February 2011

Abstract
Objectives of the study: Head and Neck squamous cell carcinoma (HNSCC) results from deregulation of multiple signaling pathways leading to tumor cells acquiring proliferative, invasive, angiogenic and metastatic properties. Interactions between neoplastic cells and the surrounding microenvironment also play a major role in tumor progression. Recent studies have demonstrated that microRNA's (miRs) play a critical role in cancer development where they can act as oncogenes or as onco-suppressors. A microRNA array analysis of a panel often HNSCC cell lines reveled that miR-34a is significantly downregulated in all these cell lines as compared to normal human oral keratinocyes (HOK). In addition, miR-34a expression was also downregulated in highly angiogenic endothelial cells (endothelial cells overexpressing Bcl-2; EC-Bcl-2) as compared to normal human endothelial cells. However, little is known about the role of miR-34a in HNSCC tumor growth and tumor angiogenesis. In this study, we examined if dysregulation of miR-34a in HNSCC promotes tumor growth and tumor angiogenesis.
Methodology: The study was performed using a panel of established human head & neck cancer cell lines. miRs expression in tumor and endothelial cells was examined by miR-arrays and further validated by real time PCR. Lipofectamine-2000 was used to transfect miR-34a in 2 HNSCC cell lines (UM-SCC-74A and UM-SCC-47) and human endothelial cells. Cell-proliferation assay was performed by MTT and colony formation assay. Tumor cell and endothelial cell motility was assessed by scratch assay. Expression of miR-34a downstream mediators was measured by Western blot.
Results: Ectopic expression of miR34a significantly inhibited cell proliferation of UM-SCC-74A cells (52% and 58% on days 2 and 4) and UM-SCC-47 cells (43% and 47% on days 2 and 4). In addition, enhanced expression of miR34a in UM-SCC-74A and UM-SCC-47 cells significantly inhibited tumor cell colony formation and tumor cell migration. Similar to tumor cells, miR-34a significantly inhibited EC-Bcl-2 proliferation and migration by down regulating c-met, Bcl-2 expression and upregulating phospho p38 MAPK expression.
Conclusion: These findings indicate that dysregulation of miR-34a expression is common in HNSCC and modulation of miR34a activity might represent a novel therapeutic strategy for the treatment of head and neck cancers.
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 LB-354.
Abstract LB-355: miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis
Authors: Gebeshuber Christoph 
Published: February 2011

Abstract
Several microRNAs (miRNAs) have recently been described as crucial regulators of epithelial-to-mesenchymal transition (EMT) and metastasis. By comparing the expression profiles of miRNAs, we found up regulation of miR-29a in mesenchymal, metastatic RasXT cells relative to epithelial EpRas cells. Overexpression of miR-29a suppressed the expression of tristetraprolin (TTP), a protein involved in the degradation of messenger RNAs with AU-rich 3′-untranslated regions, and led to EMT and metastasis in cooperation with oncogenic Ras signalling. We also observed enhanced miR-29a and reduced TTP levels in breast cancer patient samples, indicating relevance for human disease. Previously, miR-29 family members were shown to have tumor-suppressive effects in haematopoietic, cholangiocytic and lung tumors. Therefore, miRNAs can act as either oncogenes or tumor suppressors, depending on the context.
In addition to miR-29a we found several other miRNAs in our miRNA profiling analyses of cell lines and murine tumors and could confirm them and regulated targets in human breast cancer patient samples.
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 LB-355.
Abstract LB-388: Macrophage migration inhibitory factor (MIF) plays a role in proliferation, differentiation, and survival of Ewing tumor cells through the activation of several kinases
Authors: Kang Hyung-Gyoo , Liu Xian Fang , Sorensen Poul HB , Triche Timothy J. 
Published: February 2011

Abstract
Cytokines and chemokines are involved in various mechanisms of cell signaling networks, which control cell growth, proliferation, differentiation, and survival. In normal cells, expression of cytokines and their downstream cell signaling pathways are tightly and accurately regulated. However, it has been shown that cytokine signaling pathways are deregulated in many tumors. Thus, identification and understanding of deregulated cytokines and their related pathways may provide unique and promising opportunities for better-targeted therapies of cancer. In the previous experiments we showed that Macrophage migration Inhibitory Factor (MIF) is highly expressed in Ewing tumor cells and it is involved in the proliferation and survival of Ewing tumors. Our present data implies that MIF might functionally contribute to Ewing tumor cell growth, differentiation and survival through the activation of several kinases such as AMPK (AMP activated protein kinase), Paxillin and PYK2 (Protein Tyrosine Kinase2). In conclusion, coupled with earlier and present studies about MIF-dependent effects on Ewing tumors our data suggested that MIF might be involved in various pathways of Ewing tumor biology and might be a promising target of Ewing tumor cells 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 LB-388.
Abstract LB-391: The modified effect of obesity on the association between height and cancer incidence
Authors: Lee Sang-Ah , Kim Jong-Hoon , Sung Joohon 
Published: February 2011

Abstract
Height has been regarded as anthropometric marker of early-life environments and reported the association with the risk of cancer incidence and mortality although the results were not consistent for some site-specific cancers. This study was aimed to evaluate the association between height and cancer incidence among Korean and the modification effects at BMI on the association. In addition, the association between height and the mortality of 5 major cancer sites was analyzed.
The study participants of 1,067,923 Koreans (609,560 men and 458,363 women) aged 30-65 years was included in the follow-up or cancer incidence and mortality between 1993 and 2005. Study participants were divided into quartile according to their height. The lower quartile served as the reference group. Hazards ratio (HR) and 95% confidence intervals (CIs) associated with height included in the model were age, weight, cigarette smoking habits, alcohol drinking habits, physical activity, economic status, age at menarche, and menopause status.
After adjustment for all the covariates, each 5 cm increment in height was associated with 5% and 7% higher risk of overall cancer incidence in men and women, respectively. In case of site-specific cancers, a positive association was BMI (under vs. over 25 kg/m2), the effect of height on the risk of lung and prostate cancer incidence was predominantly observed among obese women only.
These results suggest the association between height and cancer incidence might be modified by BMI status.
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 LB-391.
Abstract LB-394: Marijuana use and testicular germ cell tumors
Authors: Trabert Britton , Sigurdson Alice J. , Sweeney Anne M. , Strom Sara S. , McGlynn Katherine A. 
Published: February 2011

Abstract
Introduction: Since the early 1970's the incidence of testicular germ cell tumors (TGCT) in the U.S. has been increasing, however, environmental exposures accounting for this rise have not been identified. Trends in marijuana use have also increased during this period. Chronic marijuana use has been shown to produce adverse effects on the human endocrine and reproductive systems. A prior study of marijuana use and TGCT reported a significant association among frequent and long-term current users. We aimed to evaluate the relationship of marijuana use and TGCT in an existing hospital-based case-control study conducted at the University of Texas M. D. Anderson Cancer Center.
Methods: TGCT cases diagnosed between January 1990 and October 1996 (n=187) and male friend controls (n=148) matched on age, race and state of residence were enrolled in the study. Associations of marijuana use and TGCT were estimated using unconditional logistic regression adjusting for age, race, prior cryptorchidism, cigarette smoking and alcohol intake. Associations stratified on histology (seminoma, nonseminoma) were also examined.
Results: Overall, TGCT cases were more likely to be frequent marijuana users (daily or &gt;1 day per week) than were controls [OR: 2.2, 95% CI: 1.0, 5.2]. In the analysis limited to nonseminomas, cases were significantly more likely than controls to be frequent users [OR: 3.3, 95% CI: 1.3, 8.6] and to be long-term users (10+ years) [OR: 2.3, 95% CI: 1.0, 5.8]. As the use of friend controls can bias the results of retrospective studies, we evaluated the extent to which reporting of marijuana use among the controls was consistent with data from the 1996 population-based National Survey on Drug Use and Health (NSDUH). We compared the observed number of controls who reported ever using marijuana with the expected number based on age- and race-specific proportions in the NSDUH and found no significant difference [O/E ratio: 0.96; 95% CI: 0.74, 1.22], suggesting selection or reporting bias was not an explanation for the observed associations.
Discussion: Our finding of an association between frequent marijuana use and TGCT, particularly among men with nonseminoma is consistent with the findings of a previous report. Marijuana use may be related to nonseminoma due to activation of the cannabinoid receptors during a critical time period in pubertal development; however it is also plausible that biologically active components of marijuana may function through pathways other than the endocannabinoid system. Additional studies of marijuana use and TGCT are warranted, especially studies evaluating the role of endocannabinoid signaling and cannabinoid receptors in TGCT.
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 LB-394.