bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 769: Novel cancer immunotherapeutics utilizing targeting peptides
Authors: Diaz Tracy M. , McGuire Michael J. , Brown Kathlynn C. 
Published: June 2012

Abstract
Cancer immunotherapeutics is an emerging treatment option that offers high tumor specificity and efficacy while reducing deleterious side effects. Immune therapies for cancer can be divided into two main types: active and passive. Active therapy strives to achieve a long term protective immunity against a tumor antigen while passive therapy supplies exogenous immunological reagents to provide specific anti-tumor effector functions. Both immunotherapies can be improved through the use of targeting peptides. Our lab utilizes a phage library panning method for isolation of cell-specific peptides that can be rapidly acquired without prior knowledge of cell surface receptors.
Active Immunotherapy: Cancer vaccines can elicit an immune response against tumor associated antigens that will result in tumor reduction and protective immunity. Recent studies have utilized antigen-pulsed in vitro matured DCs during vaccination for a more effective anti-cancer immune response. Several clinical trials, however, show that this method does not provide a significant therapeutic immune response. A more robust anti-tumor immune response could potentially be achieved through in vivo targeting of tumor antigens to DCs. Through the phage library panning protocol, our lab has identified 2 phage clones, XS52.1 and XS52.3, which have been shown to specifically bind to the XS52 immature dendritic cells. The XS52.3 phage clone has been further shown to bind bone marrow dendritic cells (BMDCs) from both Balb/c and C57BL/J6 mice. While current data suggests these phage clones are capable of binding DCs in vitro, future studies will determine if these peptides can be used to target antigen to DCs in vivo for vaccination.
Passive Immunotherapy: Monoclonal antibodies directed against tumor associated antigens have been successfully used in clinical settings, but problems remain with identifying and validating new antigen targets. Modification of the antibody scaffold for distinct applications can also be problematic. Using our phage display panning protocol, we have identified ligands of high affinity and specificity against a panel of human non-small cell lung cancer (NSCLC) cell lines. Furthermore, these peptide targeting ligands can be chemically synthesized and easily modified for different uses. For example, synthetic peptide ligands have been used to direct antibody dependant cellular cytotoxicity through the use of biotinylated tetrameric peptides and anti-biotin antibodies. These results suggest that peptide targeting ligands can be used to direct antibody effector functions for passive immunotherapy against cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 769. doi:10.1158/1538-7445.AM2011-769
Abstract 800: Inflammatory chemokines mediate immune surveillance of intestinal cancer
Authors: Jala Venkatakrishna R. , Mathis Steven P. , Bodduluri Sobha R. , Maturu Paramahamsa , Krishnan Elangovan , Smith Michelle E. , Chilton Paula M. , Mitchell Thomas C. , Locati Massimo , Mantovani Alberto , Bodduluri Haribabu 
Published: June 2012

Abstract
Immune system plays a dual role in cancer development and progression. Under conditions of chronic inflammation the repair response initiated by the immune system strongly promotes tumor growth. Epidemiological evidence of increased cancer incidence in organ transplant recipients and immune compromised individuals suggests a critical role for immune surveillance in keeping cancer under control. The cellular and molecular mechanisms that control tumor promoting chronic inflammation or tumor suppressing immune surveillance are unclear. Chemokines direct the migration of leukocytes to the sites of infection or injury and therefore are likely to play a central role in perpetuating tumor promoting chronic inflammation as well as orchestrating tumor eradicating immune surveillance.
D6 is a chemokine decoy receptor and an effective scavenger of inflammatory CC-chemokines. D6-knockout (D6-/-) mice showed enhanced inflammation in different models including carcinogen-induced inflammation-promoted skin cancers. In this study, we show that D6-/- mice when bred onto mice with a heterozygous mutation in the adenomatous polyposis coli (ApcMin/+) gene demonstrated reduced intestinal tumor burden and increased survival. A decrease in tumor promoting inflammation is coincidental with increased mast cells and CD8+ T cell activation profiles in tumors from the D6-/-ApcMin/+ mice compared to ApcMin/+ mice. The D6-/-ApcMin/+ mice in the context of the lymphocyte deficient, Rag2-/-background (Rag2-/-D6-/-ApcMin/+), showed a significant increase in tumor burden that is reversed by the adoptively transferred CD8+ and/or CD4+T-lymphocytes from the D6-/-ApcMin/+ mice. Chemokine levels in serum and chemokine receptor expression patterns on lymphocytes from the ApcMin/+ and D6-/-ApcMin/+ mice and the Rag2-/-D6-/-ApcMin/+ mice undergoing adoptive transfer treatments identified the increased levels of ligand-receptor pairs of LTB4/BLT1, CCL2/CCR2, and CXCL9/CXCR3 being critical in promoting tumor suppressive immune surveillance in this spontaneous tumor model. These results show that inflammatory chemokines play a protective role against progression of intestinal cancers by immune surveillance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 800. doi:10.1158/1538-7445.AM2011-800
Abstract 810: Dietary grape seed proanthocyanidins inhibit UV-induced immunosuppression through stimulation of CD8+ effector T cells and inactivation of regulatory CD4+ T cells
Authors: Vaid Mudit , Singh Tripti , Sharma Samriti , Li Anna , Elmets Craig A. , Xu Hui , Katiyar Santosh K. 
Published: June 2012

Abstract
The immunosuppressive effects of solar ultraviolet (UV) radiation, particularly UVB (290-320 nm), are well recognized. Experimental evidence indicates that UV-induced immunosuppression is a risk factor for skin cancer development, including melanoma and non-melanoma, in mice and clinical evidence suggests that it is also a risk factor in humans. Conversely, animals with an enhanced immune response exhibit a lower risk of skin tumor development on chronic UV exposure. Dietary grape seed proanthocyanidins (GSPs) have been shown to inhibit UVB-induced immunosuppression in mice; however, the cellular and molecular mechanisms underlying this inhibitory effect of GSPs are not yet clearly understood. To characterize the cell population responsible for the GSPs-mediated inhibition of UVB-induced immunosuppression, we used an adoptive transfer approach. Splenocytes and draining lymph nodes were harvested from mice that had been administered dietary GSPs, exposed to UVB, and sensitized by topical application of 2,4-dinitorfluorobenzene (DNFB) onto the UVB-exposed skin. CD8+ and CD4+ T cells were positively selected and transferred into naïve mice that were subsequently challenged by application of DNFB on the ear skin. Naïve recipients that received CD8+ T cells from GSPs-treated, UVB-irradiated donors exhibited full contact hypersensitivity (CHS) response. CHS is considered to be a prototypic T-cell mediated immune response. Naïve mice that received CD4+ regulatory T cells from GSPs-treated, UVB-exposed mice were able to mount a CHS response after sensitization and subsequent challenge with DNFB. On culture, the CD8+ T cells from GSPs-treated, UVB-exposed mice secreted higher levels of Th1 cytokines (IL-2, IFNγ) than CD8+ T cells from UVB-irradiated mice not treated with GSPs. CD4+ T cells from GSPs-treated, UVB-exposed mice secreted significantly lower levels of Th2 cytokines (IL-4 and IL-10) than CD4+ T cells from UVB-exposed mice not treated with GSPs. These data suggest that dietary GSPs inhibit UVB-induced immunosuppression by stimulating CD8+ effector T cells and diminishing regulatory CD4+ T cells in mice. This property of GSPs can be used as an alternative strategy to augment the induction of CD8+ effector T cells and to diminish the development of CD4+ regulatory T cells and that may lead to the prevention of skin cancer risk in humans.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 810. doi:10.1158/1538-7445.AM2011-810
Abstract 87: SULF2 methylation is a prognostic biomarker for lung cancer survival and increases sensitivity to camptothecin analogues via expression of ISG15
Authors: Tessema Mathewos Z. , Yingling Christin M. , Thomas Cynthia L. , Klinge Donna M. , Bernauer Amanda M. , Stidley Chris , Joste Nancy , Dahlberg Suzanne , Schiller Joan , Belinsky Steven A. 
Published: June 2012

Abstract
Heparan sulfate proteoglycans (HSPGs) serve as co-receptors for numerous signaling molecules including growth factors and cytokines. The sulfation pattern on the heparan sulfate (HS) motif is central to the interaction between HSPGs and the myriads of molecules including interferon (INF). SULF2 encodes for HS 6-O-endosulfatase enzyme that removes the 6-O-sulfate moieties from HS and regulates the specificity of this interaction. Increased expression of SULF2 promotes angiogenic and oncogenic signaling. In hepatocellular carcinoma higher expression of SULF2 is associated with worse prognosis after resection. Conversely, we recently reported that methylation-mediated SULF2 silencing is associated better survival of resected lung cancer patients. Here we show that SULF2 methylation is also a favorable survival marker in unresectable lung cancer. Furthermore, epigenetic silencing of SULF2 suppresses cell migration and induces the expression of multiple INF-inducible genes. Knocking down 80% of SULF2 expression in Calu-3 cells using siRNA resulted in 7-fold increase in the expression of INF-inducible regulator of ubiquitination, ISG15. Similarly, lung cancer cell lines with methylated SULF2 (SULF2M) on average express 60-fold higher ISG15 than cell lines with unmethylated SULF2 (SULF2U). ISG15 is a key marker for increased sensitivity of cancer cells to topoisomerase-1 inhibitors such as camptothecin and topotecan. In vitro treatment of lung cancer cell lines with camptothecin revealed a 65-fold higher sensitivity in cell lines with SULF2M and ISG15 high (ISG15H) phenotype compared to SULF2U and ISG15 low (ISG15L) cell lines. In nude mice, 10mg/kg/week topotecan treatment dramatically arrested the growth of SULF2M and ISG15H lung cancer xenografts but had no effect on SULF2U and ISG15L xenografts. Heterogeneity for ISG15 expression was also seen in primary tumors. One third of primary lung tumors have ISG15H phenotype with an average of 5-fold higher expression than the remaining 2/3rd tumors in which the ISG15 level is comparable to normal lung. Taken together these results indicate SULF2 methylation is not only a favorable prognostic marker for lung cancer, but through its association with increased expression of ISG15 could indicate a higher sensitivity to topoisomerase-1 inhibitors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 87. doi:10.1158/1538-7445.AM2011-87
Abstract 881: Polymorphisms of PUMA, a BH3-only pro-apoptotic gene, modify risk of squamous cell carcinoma of head and neck associated with HPV16 infection
Authors: Zhou ZiYuan , Li Guojun , Liu Zhensheng , Wang Li-E , Sturgis Erich M. , Wei Qingyi 
Published: June 2012

Abstract
PUMA (p53 upregulated modulator of apoptosis) and Noxa (Latin for damage), as well as their common target MCL-1 (myeloid cell leukemia 1), respond to human papillomavirus 16 (HPV16) oncoprotein E6-mediated p53 degradation or E7-mediated pRb inactivation, and therefore may alter cancer susceptibility through the PUMA (Noxa)-MCL1-apoptosis mechanism.
In this case-control study of 380 cases and 335 cancer-free matched controls, we evaluated HPV16 seropositivity and two single nucleotide polymorphisms (SNPs) in the promoter region for each gene (rs3810294 and rs2032809 for PUMA, rs4558496 and rs9957673 for Noxa, rs9803935 and rs3738485 for MCL1) to examine their possible associations with risk of squamous cell carcinoma of head and neck (SCCHN).
Of the 6 SNPs, both two SNPs of PUMA were significantly associated with 1.5-fold increased SCCHN risk in a dominant model. When we include the HPV16 seropositivity in the model, the risk of SCCHN was significantly increased in an allele-dose effect manner (Ptrend&lt; 0.0001 for each SNP, respectively). Notably, in the site-stratified analysis, oropharyngeal cancer risk was dramatically increased, particularly among minor alleles carriers having the HPV16 L1 seropositivity with OR (95%CI) of 13.8 (5.4-35.5) for rs3810294 and 8.1 (4.3-15.0) for rs2032809 (both Ptrend &lt; 0.0001). These data suggest some synergistic effects between PUMA variants and HPV16 seropositivity on susceptibility to SCCHN, especially in those cases with HPV-related oropharyngeal cancer. Additionally, the modifying effect of PUMA variants on oropharyngeal cancer associated with the HPV16 L1 seropositivity was more predominant in never-smokers, never-drinkers and young subjects. Our results suggest that PUMA promoter polymorphisms, synergistically interacting with HPV16 L1 seropositivity, modify risk of HPV-related oropharyngeal cancer. Further molecular and epidemiologic studies with larger samples are needed to validate our findings.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 881. doi:10.1158/1538-7445.AM2011-881
Abstract 902: Serum antibodies to the HPV16 proteome as biomarkers for head and neck cancer
Authors: Anderson Karen S. , Wong Jessica , D'Souza Gypsyamber , Riemer Angelika B. , Lorch Jochen , Haddad Robert , Pai Sarah , Longtine Janina , Bryan Janine , McClean Michael , Labaer Joshua , Kelsey Karl , Posner Marshall R. 
Published: June 2012

Abstract
Purpose: Human papillomavirus (HPV) type 16 is associated with oropharyngeal carcinomas (OPC). Antibodies (Abs) to HPV16 E6 and E7 oncoproteins have been detected in patient sera, however Abs to other early HPV-derived proteins have not been well explored.
Experimental Design: Abs to the HPV16 proteome were quantified using a novel multiplexed bead assay, using C-terminal GST fusion proteins captured onto Luminex beads. Sera were obtained from two cohorts of untreated OPC patients with known Abs to HPV16 Virus-Like Particles (VLP) (N=10), HPV18 VLP (N=10), healthy controls (N=20), and from a validation cohort of untreated patients with OPC (N=30), partners of patients with HPV16+ OPC (N=11), and healthy controls (N=30).
Results: OPC patients in the known VLP+ cohort had elevated serum Abs to HPV16 E1, E2, E4, E6, and E7, and L1 antibody levels but not E5. The ratios of specific median fluorescent intensity (MFI) to p21-GST compared to controls were: E1 50.7 vs. 2.1; E4 14.6 vs. 1.3; E6 11.3 vs. 2.4; E7 43.1 vs. 2.6; and L1 10.3 vs. 2.6 (each p&lt;0.01). No cross-reactivity was detected between HPV16 E7 and HPV18 E7 Abs. In the validation cohort, HPV16 E1, E2, and E7 antibody levels were most significantly elevated compared to healthy control samples (p&lt;0.0001) and partners of OPC patients (p&lt;0.01).
Conclusion: A novel multiplexed bead assay for the detection of HPV16-specific Abs demonstrates that patients with HPV16+ OPC have detectable Abs to multiple early genes, in particular E1, E2 and E7. These Abs are potential biomarkers for HPV-associated OPC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 902. doi:10.1158/1538-7445.AM2011-902
Abstract 912: The tumor promoting activity of the prostaglandin E2 EP4 receptor in mouse skin
Authors: Simper Melissa S. , Bowen Rebecca A. , Surh Inok , Fischer Susan M. 
Published: June 2012

Abstract
Chronic inflammation has recently been suggested to be involved in cancer development, and cyclooxygenase-2 (COX-2), a key mediator of the inflammatory response, is known to be upregulated in several cancers. COX-2 is responsible for the production of prostaglandins, and prostaglandin E2 (PGE2) is the major prostaglandin involved in inflammation. PGE2 binds to four receptors (EP1-EP4), and the EP4 receptor has recently been shown to be important in carcinogenesis, depending on the tissue in which it is expressed. To determine the role of EP4 in skin carcinogenesis, transgenic mice were generated that overexpress EP4 in the basal layer of the epidermis under the control of the bovine keratin 5 promoter (BK5.EP4 Tg). Using a two-stage chemical carcinogenesis protocol, the BK5.EP4 Tg mice were shown to develop both papillomas and squamous cell carcinomas earlier than wild type (WT) mice. However, a tumor observed before 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment on one BK5.EP4 Tg mouse suggested that TPA was not necessary for the promotion of the tumors. Therefore a 7,12-dimethylbenz[a]anthracene (DMBA)-only carcinogenesis protocol was performed, and by 30 weeks, the BK5.EP4 Tg mice developed more carcinomas compared to none on the WT mice. Immunohistochemistry performed on DMBA-treated mice demonstrated that the BK5.EP4 Tg epidermis began to detach 48 hours after treatment with total detachment occurring 5 days after treatment, while WT mice had only increased epidermal thickening. Caspase-3, MMP-9, and MMP-7 expression also were upregulated in the BK5.EP4 Tg mice at the same time detachment of the epidermis was occurring. Ki67 analysis showed an initial increase in proliferation in WT mice that slowly declined back to normal levels, while the BK5.EP4 Tg mice instead had a sustained increase in proliferation, which occurred during reepithelialization of the epidermis. These data suggest that overexpression of EP4 in the mouse skin can increase tumorigenesis, possibly through the wounding of the skin and the subsequent epidermal regeneration acting as a tumor promoter. Supported by CA100140.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 912. doi:10.1158/1538-7445.AM2011-912
Abstract 930: Reprogramming the transcriptional response to hormone through functionally-distinct classes of gene enhancers in prostate cancer cells
Authors: Garcia-Bassets Ivan , Wang Dong , Benner Chris , Wenbo Li , Su Xue , Glass Christopher K. , Rosenfeld Michael G. , Fu Xiang-Dong 
Published: June 2012

Abstract
Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell type-specific gene expression programs; however, the potential that there are pre-established enhancers that permit alternative signal-dependent transcriptional responses has remained unexplored. Here we present evidence that cell lineage-specific factors, such as FoxA1, which contribute to the activation of cell-type specific enhancers by selectively favoring the recruitment of key regulated transcription factors such as the androgen receptor (AR) in prostate cancer cells, can simultaneously restrict these same factors from activating additional (alternative) pre-established but yet inactive enhancers, thus licensing specific signal-activated responses and restricting others. Importantly, these alternative hormonal responses are linked to distinct structural and functional classes of enhancers. Consequently, FoxA1 down-regulation, an unfavorable prognostic sign in some sets of advanced prostate tumors, causes a massive switch in AR binding from one functional enhancer class to another, which massively reprograms the hormonal response. The molecular basis for this switch lies in the release of FoxA1-mediated “restriction” of AR binding to the new enhancer class that requires no apparent nucleosome remodeling for their activation.
Multiple global analyses of enhancer formation, structure, looping, and activation were combined to support these conclusions, including: H3K4me1/me3, H3K27ac, and H4K4ac mapping (ChIP-seq); nucleosomal H3K4me2 mapping (nucleosomal ChIP-seq); FoxA1, AR, p300, and MED12 mapping (ChIP-seq), also supported by the 3C assay; enhancer ncRNA or eRNAs generation analysis (GRO-seq); and gene expression analysis (microarray and GRO-seq).
Together, these findings reveal a large repository of pre-determined enhancers in the human genome that can be dynamically tuned to induce alternative gene expression programs, which -we speculate- may underlie many sequential gene expression events in development or during cancer progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 930. doi:10.1158/1538-7445.AM2011-930