bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4722: Evaluation of common genetic variation in 1,300 cancer-related candidate genes and endometrial cancer risk
Authors: Yang Hannah P. , Spurdle Amanda , Gaudet Mia M. , Brinton Louise A. , Lissowska Jolanta , Peplonska Beata , Sherman Mark , Webb Penny , Ferguson Kaltin , O'Mara Tracy , ANECS ‘ , Chanock Stephen , Garcia-Closas Montserrat 
Published: February 2011

Abstract
Background: Endometrial cancer genetic susceptibility studies have largely focused on genes in the sex steroid hormone, checkpoint, and cell-cycle pathways, but single nucleotide polymorphisms (SNPs) in genes involved in other cancer-related pathways might also influence risk.
Methods: We investigated the association between endometrial cancer risk and ∼29,000 SNPs in over 1,300 cancer-related candidate genes in the inflammation, metabolism, and other carcinogenic pathways in the Polish Endometrial Cancer Study (PECS), a population-based investigation involving 417 cases and 407 controls. TagSNPs were located in the respective gene or within 10 kb or 5 kb downstream; had a minor allele frequency (MAF) &gt;5% in various ethnic groups; and were not represented by a current tag SNP in linkage disequilibrium (LD; r2&gt;0.80). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression, adjusting for age (5-year categories). The most significant finding was followed up in the Australian National Endometrial Cancer Study (ANECS), a population-based case-control study of 815 cases and 822 controls.
Results: In PECS, we found three SNPs in two loci associated with endometrial cancer risk at P&lt;0.0001. Two highly correlated SNPs in IQGAP1, rs2601207 (OR = 0.65; 95% CI: 0.53 - 0.81, P trend = 6.0 × 10−5) and rs6496677 (0.66; 0.54 - 0.81, P trend = 8.0 × 10−5), were associated with a decreased risk. In addition, a variant in UBE3A, rs4445877, was associated with increased risk (1.53; 1.24 - 1.90, P trend = 9.0 × 10−5). We followed up the rs2601207 association in ANECS and observed a non-significantly decreased risk (0.90; 0.77 - 1.05, P trend = 0.18). The pooled per allele OR was 0.81 (95% CI: 0.72 - 0.92), P trend = 0.001); however, there was evidence for heterogeneity by study (P-heterogeneity = 0.01).
Conclusion: Data from PECS suggests associations between endometrial cancer risk and variants in IQGAP1, a gene that is a key mediator in several cellular processes related to carcinogenesis, and UBE3A, encoding ubiquitin protein ligase 3A involved in the degradation of cancer-associated proteins such TP53. The association with IQGAP1 was not confirmed in a larger study population; and further studies are needed to follow up other potential associations between endometrial cancer risk and cancer candidate genes.
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 4722.
Abstract 4745: A whole genome association study and identification of a locus for histiocytic sarcoma in the flat-coated retriever
Authors: Shearin Abigail L. , Schmidt Emmett V. , Parker Heidi G. , Mellersh Cathryn S. , Breen Matthew , Ostrander Elaine A. 
Published: February 2011

Abstract
Histiocytic sarcoma (HS) is a cancer characterized by unregulated proliferation of histiocytes. In the flat-coated retriever (FCR), the primary tumor site is frequently appendicular with a high rate of local and distant metastases. The disease occurs with a high prevalence in the FCR, accounting for approximately 40% of all cancers in the breed and 18% of disease-related deaths in a UK cohort. Breed-specific prevalence in FCRs indicates a strong genetic predisposition. Our goal is to identify the underlying loci and causal mutations associated with HS in the FCR.
A whole genome association study (GWAS) using the Illumina Canine SNP20 BeadChip was performed using 98 DNA samples from FCR collected from the United States (48 cases and 50 unaffected controls over the age of ten yrs). Of the 23,000 SNPs genotyped, 17,000 were informative in the FCR. A single-marker chi-squared analysis using EMMA to correct for population structure and kinship yielded an association with the HS phenotype (p=2.33×10-5). Including the flanking markers, the associated region spans 12 Mb and includes several candidate genes of interest. To reduce this critical interval, ABI SNPlex genotyping and candidate gene sequencing is in progress.
Our current data distinguish HS in the FCR from the related disease malignant histiocytosis (MH) found in Bernese mountain dogs (BMD). MH is a disseminated histiocytic cancer with primary tumor sites usually occurring in visceral organs. Our data suggest that HS in the FCR is not a localized form of MH. GWAS analyses for both breeds indicate that the major contributing heritable factors of MH in the BMD differ from those for HS in the FCR. Given the different behaviors of the cancers between the two breeds and the different heritable loci associated with them, our current evidence distinguishes them as separate diseases.
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 4745.
Abstract 4748: Identification of HLA-A*0201 and A*2402-restricted epitope peptides derived from mucin 5AC (MUC5AC) gene expressed in human pancreatic cancer as a potential target for immunotherapy
Authors: Yamazoe Sadaaki , Tanaka Hiroaki , Iwauchi Takehiko , Noda Eiji , Amano Ryosuke , Kubo Naoshi , Muguruma Kazuya , Inoue Toru , Takashima Tsutomu , Yamada Nobuya , Yashiro Masakazu , Maeda Kiyoshi , Onoda Naoyoshi , Sawada Tetsuji , Nakata Bunzo , Ohira Masaichi , Ishikawa Tetsuro , Hirakawa Kosei 
Published: February 2011

Abstract
MUC5AC was previously identified to be de novo expressed in the majority of pancreatic ductal adenocarcinoma. For the development of pancreatic cancer immunotherapy, we studied the significance of MUC5AC expressed in pancreatic ductal adenocarcinoma and the capability of MUC5AC as a target for immunotherapy of pancreatic cancer. By immunohistochemical analysis of 102 specimens, MUC5AC is absent from all cell types of the normal pancreas, but arise de novo in 85% of invasive ductal adenocarcinoma. Clinicopathlogically, tumors with lymph node metastasis had significantly higher expression of MUC5AC than those without node metastasis. To validate the potentiality of cancer vaccine, we have searched for possible epitope peptides that can elicit cytotoxic T lymphocytes (CTL) to MUC5AC. We screened 20 candidate peptides derived from MUC5AC gene sequence for each of human leukocyte antigen (HLA) - A*0201 and A*2402. As a result, we successfully established CTL clones stimulated by MUC5AC-A02-1398 (FLNDAGACV) and MUC5AC-A24-716 (TCQPTCRSL) peptide that have specific cytotoxic activities against each of the HLA-A*0201 and A*2402-positive target cells pulsed with the candidate peptide. Subsequent analysis of each CTL clones also revealed their cytotoxic activities against pancreatic cancer cells expressing MUC5AC. A cold target inhibition assay further confirmed that each CTL clones specifically recognized the major histocompatibility complex (MHC) class I-peptide complex. Our results suggested that MUC5AC is a novel tumor-associated antigen recognized by CTL, and MUC5AC-A02-1398 (FLNDAGACV) and MUC5AC-A24-716 (TCQPTCRSL) are HLA-A*0201 and A*2402-restricted epitope peptides that can induce potent and specific immune responses against pancreatic cancer cells expressing MUC5AC.
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 4748.
Abstract 4752: Induction of cytotoxic T lymphocytes primed with tumor RNA-loaded dendritic cells in esophageal squamous cell carcinoma: Preliminary step for DC vaccine design
Authors: Moaven Omeed , Gholamin Mehran , Farshchian Moein , Mahmoudi Mahmoud , Sankian Mojtaba , Memar Bahram , Forghani Mohammad N. , Malekzadeh Reza , Abbaszadegan Mohammad R. 
Published: February 2011

Abstract
Backgrounds: Dendritic Cells (DC) are potent antigen presenting cells with the ability to prime naïve T cells and convert them to cytotoxic CTL. We evaluated the capability of autologous DCs transfected with total Tumor and normal RNA to induce cytotoxic CTL as the preliminary step to design DC-based vaccine in the esophageal squamous cell carcinoma (ESCC).
Methods: Monocytes-derived DCs were electroporated with either total tumor RNA or normal RNA. T cells were then primed with tumor RNA transfected DCs and lysing effects of the generated CTL were measured with Cytotoxicity assay and IFN-γ Release Elispot Assay.
Results: Cytotoxicity against DCs loaded with tumoral RNA was induced (%24.8±5.2 SEM) while in normal RNA-loaded DCs it was minimal (%6.1±2.4 SEM) and significantly lower (p &lt; 0.05). INF-γ secretion was more than 2-folds higher in tumoral RNA-loaded DCs when compared with normal RNA-loaded DCs (p &lt; 0.05).
Conclusion: Electroporating DCs with tumor RNA made tumor antigen presenting cells that enhanced cytotoxicity effects of T cells against ESCC. This may be a useful autologous ex vivo screening tool for confirming the lytic effects of primed T cells on tumor and evaluate probable further adverse effects on noncancerous tissue. These data are a crucial preliminary step to establish a total tumor RNA-pulsed DC vaccine therapy of ESCC.
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 4752.
Abstract 4755: Importance of an induction dose to the immunogenicity of cancer vaccines: A reverse translational study
Authors: Berd David A. , Braun Donald , Mokyr Margalit B. 
Published: February 2011

Abstract
We have described a human cancer vaccine consisting of autologous, irradiated melanoma cells modified with the hapten, dinitrophenyl (DNP), and mixed with BCG. Because of its immunopotentiating effect, low dose cyclophosphamide (CY) was administered 3 days before the first of a series of vaccine injections. The vaccine induced T cell immunity to both haptenized and unmodified autologous melanoma cells; clinical effectiveness was suggested by tumor regression in some stage IV patients and an unexpectedly high proportion of 5-year survivors in stage IIIB and IIIC patients. A serendipitous finding from these studies was the critical importance of what we came to call an “induction dose” of vaccine - a single injection of irradiated, autologous melanoma cells without BCG 5-7 days prior to CY. Patients who received a properly timed induction dose had more intense T cell responses (positive DTH to unmodified melanoma cells 73% vs. 20%, p&lt;.01) and were more likely to survive 5 years (51% vs. 33%, p=.007) than those who did not. To support this finding in a controlled experimental system, we developed a mouse model using the mammary carcinoma, 410.4. After injection of 410.4 cells into the mammary fat pads, primary tumors developed and were excised. Then we assessed the anti-metastatic activity of low dose CY followed by a DNP-modified vaccine prepared and administered in a manner comparable to the human melanoma vaccine. The published study showed that this regimen significantly prolonged tumor-free survival in the mice while CY followed by a control vaccine (irradiated, non-haptenized cells) did not. To mimic the induction dose used in the clinical trial, a cohort of mice was injected with irradiated, DNP-modified tumor cells without BCG 3-7 days prior to CY. The relapse-free survival (RFS) of mice receiving the induction dose (N=41) was significantly longer (p &lt; .01) than that of mice receiving DNP-vaccine without the induction dose (N=27) (e.g., RFS day 37: CY+irradiated vaccine=30.8%, CY+irradiated-haptenized vaccine=40.7%, CY+induction dose+ irradiated-haptenized vaccine=53.7%). In this reverse translational model, the murine experiments corroborated a serendipitous clinical observation. Taken together our results suggest a new strategy for increasing the effectiveness of cancer vaccines.
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 4755.
Abstract 4756: Anti-melanoma-specific humoral immune responses in vitro in patients vaccinated with DC-rIL-2-VMO
Authors: Berenji Manijeh , Alam Khorshed , Somasundaram Raj , Wallack Marc K. 
Published: February 2011

Abstract
Introduction: DC-rIL-2-VMO, an allogeneic cellular melanoma vaccine consisting of five melanoma cell lines, a recombinant vaccinia virus encoding for IL-2, as well as dendritic cells, has previously been shown to generate a potent cellular response in murine tumor models. We now demonstrate that this vaccine also has the capacity to generate a sustained humoral response in vitro.
Methods: To detect anti-tumor antibodies in pre- and post-vaccinated melanoma patients’ sera, a mixed hemadsorption assay (MHA) was used. The binding of human antibody from diluted patients’ sera (1:05, 1:15 and 1:45) to cultured melanoma cells (Mel-2, Mel V, GLM-2 and KFM cells) was determined as indicator cells, sheep red blood cells (SRBC) coated sequentially with mouse anti-SRBC sera, goat sera against mouse sera, and mouse anti-human IgG sera to detect binding of human anti-melanoma antibodies.
Results: Out of four patients evaluated with Stage IIIA-C and Stage IV resected with no evaluable disease (NED), three patients’ post-vaccination sera showed antibodies specifically binding to melanoma cell lines. Antibodies from two of the patients’ sera showed moderate to strong binding to three different melanoma cell lines (Mel 2, Mel V and GLM-2). Additionally, antibodies from patients’ sera and sera from two normal healthy donors did not show any binding to colorectal carcinoma (SW1116) cells (CRC), a negative control.
Conclusions: Treatment of patients with Stage IIIA-C and Stage IV melanoma resected to be NED with DC-rIL-2-VMO induced a tumor-specific antibody response. The presence of these anti-melanoma antibodies suggests that this vaccine may be effective in slowing the progression of melanoma in some patients via cellular and humoral immune mechanisms. DC-rIL-2-VMO has been FDA-approved for Phase I trials.
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 4756.
Abstract 4758: A new syngeneic MYCN-overexpressing neuroblastoma mouse model and MYCN-DNA vaccine
Authors: Stermann Alexander , Huebener Nicole , Seidel Diana , Shibina Anastasia , Fest Stefan , Gaedicke Gerhard , Lode Holger N. 
Published: February 2011

Abstract
Neuroblastoma (NB) is the most common solid extracranial tumor in childhood. High-level expression of MycN caused by amplification of the gene plays an important role in maintaining the malignant phenotype of NB and is the most significant marker for poor prognosis overall. Recent studies suggested that MYCN is a suitable target for immunotherapy, but up to now, a syngeneic NB mouse model over expressing MYCN and is not available to examine immunotherapeutic strategies in vivo.
Here, we report the development of a tetracycline inducible MYCN expressing murine NB cell line syngeneic to A/J mice and a new MYCN-DNA vaccine. The murine NB cell line C1300, syngeneic to A/J mice, was stably transfected with a tetracycline inducible MYCN expression vector system T-RExTM (Invitrogen). Stable transfection was verified by real-time PCR and Western-Blot, revealing significant high expression levels of MYCN RNA and protein, respectively. Characterization of the murine MYCN expressing cells in vitro and in vivo will be reported.
Furthermore, a new MYCN-DNA vaccine, based on epitopes encoding for three peptides from the murine MYCN protein sequence with high affinity to the A/J mouse MHC class I allele H2-Kk, was designed and tested in vivo for its ability to induce an antigen-specific immune response. Lymphocytes isolated from A/J mice vaccinated with the MYCN minigen vaccine effectively lysed wild type C1300 cells in cytotoxicity assays in contrast to lymphocytes from control mice. Additionally, lymphocytes from minigene vaccinated mice produced significantly higher amounts of IFN-γ after stimulation with irradiated C1300 cells, than lymphocytes from control mice, indicating the induction of cytotoxic T lymphocytes by the vaccine that actively kill even parental C1300 tumor cells with relatively low MYCN expression. We suspect that this effect will be enhanced when the newly established high MYCN-expressing C1300 cells are employed in a similar cytotoxicity assay. Results to support this hypothesis will be reported at the meeting.
In summary, we report the development of a new MYCN-DNA vaccine and a murine tetracycline inducible MYCN NB cell line providing an important new syngeneic mouse model for in vivo evaluation of new immunotherapeutic strategies.
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 4758.
Abstract 4760: A novel immune potentiating strategy for cancer vaccine
Authors: Qin Hong , Cha Soung-chul , Qin Xiao-feng , Liu Yong-Jun , Kwak Larry W. 
Published: February 2011

Abstract
A major obstacle for translational research of cancer vaccine is the weak immunogenicity of tumor antigens. Thus, the development of new, more potent strategy that aims at breaking such an immune tolerance is a prerequisite of vaccine therapy. Here we show that the unexpected effect of inducing sterile inflammation at vaccination sites by myotoxins potentiated induction of tumor-specific immunity by genetic vaccines and converted a non-immunogenic lymphoma idiotype antigen into a tumor rejection vaccine. This potent immunostimulatory effect was immune-mediated, requiring recruitment of dendritic cells (DC). Sterile inflammation induced by myotoxins was associated with upregulation of chemokines, proinflammatory cytokines, Toll-like receptors and their endogenous ligands, and activation of innate immunity. Mechanistic experiments in vivo also elucidated the requirement for genes triggering DC maturation including TLR signaling and CD40. These studies suggest that inducing sterile inflammation at vaccination sites generates a favorable microenvironment that promotes adaptive immunity. This novel mechanism of immune potentiation may be exploited for development of adjuvants for vaccines against cancer.
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 4760.
Abstract 4777: Human suppressor of cytokine signaling 1 controls immunostimulatory activity of monocyte-derived dendritic cells
Authors: Hong Bangxing , Ren Wenhong , Song Xiao-Tong , Evel-Kabler Kevin , Chen Si-Yi , Huang Xue F. 
Published: February 2011

Abstract
Dendritic cell (DC)-based tumor vaccines have only achieved limited clinical efficacy, underscoring the limitation of stimulatory strategies to elicit effective cytotoxic T lymphocyte (CTL) responses against self-tumor-associated antigens. Here, we investigate the role of human suppressor of cytokine signaling 1 (SOCS1), a feedback inhibitor of the Janus-activated kinase/signal transducer and activator of transcription signaling pathway, in regulating antigen presentation by human DCs (hDC). We find that human SOCS1 (hSOCS1)-silenced DCs have an enhanced stimulatory ability to prime self-antigen-specific CTLs in vitro and in a severe combined immunodeficient-hu mouse model. Human CTLs activated by SOCS1-silenced DCs, but not wild-type DCs, have an active lytic activity to natural antigen-expressing tumor cells. We further find that the capacity of hDCs to prime CTLs is likely controlled by SOCS1-restricted production and signaling of proinflammatory cytokines, such as interleukin-12. These results indicate a critical role of hSOCS1 in negatively regulating the immunostimulatory capacity of DCs and imply a translational potential of this alternative SOCS1 silencing strategy to develop effective DC vaccines.
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 4777.