bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5384: Frequency of gene allelic variants of the PAP prostate tumor antigen and association with immune response following antigen-specific genetic vaccination
Authors: Becker Jordan T. , McNeel Douglas G. 
Published: August 2012

Abstract
Prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) are target antigens in genetic vaccines (viral and DNA plasmid vaccines) being evaluated as treatments for prostate cancer. Amino acid allelic variants and different splicing variants of each protein have been identified as part of the human genome sequencing project. We hypothesized that allelic variants in the coding sequence of one of these target proteins in a vaccine recipient, different from the amino acid sequence of the gene encoded by the vaccine, could account for some immune responses observed following genetic vaccination. Such a finding would be essentially analogous to xenoantigen vaccination approaches using highly homologous antigens. In this report, we used direct Sanger sequencing to identify allelic variations in the genes encoding PAP and PSA from 33 patients with prostate cancer who had been previously immunized with a DNA vaccine encoding PAP. The goal of this study was to identify the frequency of variants encoding amino acid changes for two common tumor antigens, and to specifically determine if PAP-specific amino acid variants were more frequent in patients with evidence of immunological response following genetic vaccination and whether these responses localized to regions of allelic variance. Three synonymous coding mutations within the coding sequence of PAP were observed, one of which was observed in 10/33 patients (30.3%), another in 15/33 patients (45.5%), and another in 17/33 patients (51.5%). These variants appear to be linked, as 9 patients possessed all three. No non-synonymous coding mutations were identified. Thus, while a small and somewhat homogeneous patient population, these findings suggest that PAP amino acid variants may be uncommon and immune responses observed are indeed reactive to the host PAP amino acid sequence, not to antigen amino acid variants. Studies are currently underway to alternatively determine whether immune responses were elicited to peptides spanning four known splice variants of PAP. In contrast, we observed four synonymous coding mutations as well as three non-synonymous coding mutations among the five exons of the non-target antigen PSA. Synonymous or non-synonymous mutations were detected in 11/33 individuals (33.3 %). However, while more variations were observed, each occurred in a smaller frequency of patients and did not appear to be linked. The more heterogeneous sequence of PSA may warrant further investigation to determine whether immune responses elicited by genetic vaccines encoding PSA are reactive to host or vaccine-encoded epitopes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5384. doi:1538-7445.AM2012-5384
Abstract 5385: Effect of lenalidomide on antileukemia activity in vitro against adult T-cell leukemia (ATL)
Authors: Kitagawa Yukiko , Matsuoka Masao , Mitani Shohei 
Published: August 2012

Abstract
Background: Lenalidomide is an FDA approved agent for del 5q myelodysplastic syndromes and in combination with dexamethasone for previously treated multiple myeloma. Recently, phase II clinical trial has shown its anti-tumor activity against recurrent and refractory T-cell lymphomas. However, the mechanism underlining its effect is poorly understood. Adult T-cell leukemia (ATL) is a mature T cell malignancy caused by Human T-cell leukemia virus type I (HTLV-I) that is endemic in southwestern Japan, the Caribbean islands and Central Africa, and it still remains as one of the most difficult malignancies to be cured. We have evaluated the anti-ATL activity of lenalidomide in vitro using HTLV-I positive cell lines. Methods: The effect of lenalidomide (10-3-102µM) and Fas antibody (25-400 ng/mL) was assessed on the proliferation of HTLV-I positive cell lines by CellTiter-Glo Luminescent Cell Viability Assay. The cytotoxic effect against HTLV-I positive cell lines of lenalidomide on IL-2 primed peripheral blood mononuclear cells (PBMNCs) as well as sorted CD56 positive and CD3 negative cells from IL-2 primed PBMNCs from healthy volunteers was studied by 51Cr releasing assay. Results: Lenalidomide alone did not inhibit cellular proliferation. Even 6 day incubation did not inhibit or stimulate proliferation of HTLV-1 positive cell lines. Cytotoxic activity of IL-2 primed PBMNCs from healthy volunteers against HTLV-I positive cell lines was enhanced by lenalidomide. Sorted NK cells have also shown enhanced cytotoxic activities on HTLV-1 positive cells. That effect was observed regardless of Tax or cellular FLICE-inhibitory protein (cFLIP) expression. Therefore, even Fas resistant HTLV-1 positive cell lines were succumbed to death by enhanced cytotoxicity by lenalidomide, whereas lenalidomide did not interact Fas inducing apoptotic pathways. Conclusions: These results have shown that lenalidomide enhances cytotoxic effects against HTLV-I positive cells, without direct anti-proliferative effect on those cell lines. That effect was mediated through CD56 positive and CD3 negative cells stimulated by lenalidomide. Further study is now on-going to elucidate the mechanism of those actions in an in vivo setting.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5385. doi:1538-7445.AM2012-5385
Abstract 5387: Exploring effects of nanosecond and microsecond pulsed electric field ablation in a rat orthotopic hepatocellular carcinoma model
Authors: Chen Ru , Sain Nova M. , Beebe Stephen J. , Long Gary , Shires Peter 
Published: August 2012

Abstract
Hepatocellular carcinoma (HCC) is the third most common cancer in the world. A diagnosis of HCC carries a guarded prognosis, especially when metastasis is documented. Reliable, curative treatment for very early, early, and intermediate stages is still an inconsistent ideal. Nanosecond (ns), or microsecond (μs) pulsed electric fields (PEFs) that produce irreversible electroporation (IRE) could be used to ablate local tumor masses through minimal invasive or open surgery delivery. Both nsPEFs and μsPEFs induce permanent permeabilization of cells resulting in cell death without any thermal effect. NsPEFs can also impact intracellular organelles and induce apoptosis. Previous studies indicated under certain condition, there was a protective tumor response following nsPEFs treatment in mouse subcutaneous HCC model. In these studies, we specifically test the efficacy of nsPEFs and μsPEFs in an orthotopic HCC rat tumor model. N1S1 cells stably transfected with luciferase were used to generate tumors. Orthotropic insertion of transfected N1S1 HCC cells in Sprague Dawley rat livers was used as the model. Different pulses numbers, rise times and pulse durations were applied. The effect on treated tumor tissue suggests that a single treatment of 500 or 1000 100ns pulses with either slow (50ns) or fast (10ns) rise times and 50 kV/cm can eliminate HCC tumors. Continuous delivery of eighty 100μs microsecond pulses at 2.5 kV/cm dramatically reverses lesion enlargement. 1000 pulses of 100 ns PEFs with fast rise times provoke an innate immune response. Immune responses in this orthotopic HCC model are still under investigation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5387. doi:1538-7445.AM2012-5387
Abstract 5389: 3M-011, a toll-like-receptor-7/8 agonist, as immunological adjuvans in combined therapy of gastrointestinal tumors
Authors: Schoelch Sebastian , Rauber Conrad , Koch Moritz , Weitz Jürgen , Huber Peter E. 
Published: August 2012

Abstract
Background: Although there are reports about spontaneous regressions in advanced cancer stages, in most cases the immune response to solid tumors is unable to stop the progression. This immune response is mediated mainly by effectors of the cellular immune system, specifically NK cells and monocytes/macrophages, which are activated by the binding of antigens to toll-like-receptors. 3M-011, an agonist to TLR-7/8 of this sub-family of pattern recognition receptors (PRRs) may be able to boost the antitumoral immune response, especially in combination with other immunostimulatory treatments such as monoclonal antibodies or ionizing radiation. Materials/Methods: In vivo experiments comprised hetero- and orthotopic mouse models of colorectal cancer evaluating 3M-011, m225 (mouse IgG to EGFR) and photon irradiation alone or in combination. End-points were tumor growth, metastasis and tumor cell dissemination. Mice with complete regressions were re-challenged with tumor cells to evaluate the immunization effect of the therapeutic combination. The cytotoxic activity of various immune cell populations (NK cells, CD-8+ T-cells, macrophages) against gastrointestinal cancer cell lines was quantified in 51Cr release assays. Interactions between these subpopulations were investigated by co-culture experiments. NfkB-Activation was quantified by luciferase-based NfkB reporter assays. Results: A distinct growth retardation for subcutaneous tumors and reduction in metastastic activity of orthotopic tumors was demonstrated in vivo. The combination of the TLR-7/8 agonist and m225 or photon irradiation was shown to be over-additive. Mice with complete regressions after radio-immuntherapy showed distinct anti-tumor immunity when re-challenged with tumor cells as compared to control animals. In vitro assays revealed NK cells in combination with monocytes/macrophages as main effectors of the TLR-mediated early immune response followed by T-cell mediated adaptive immune response. Both effects are controlled by plasmacytoid dentritic cells. On a cellular level, NfkB was shown to be the pivotal pathway of the TLR-mediated immunostimulatory effects as well as the combined therapy effects. Conclusion: The addition of a TLR-7/8 agonist to radiotherapy and antibody therapy can achieve supra-additive therapeutic effects by boosting the immune response to the tumor. Therefore, the addition of a TLR-7/8 agonist to the treatment of advanced gastrointestinal cancers is a promising approach and merits further evaluation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5389. doi:1538-7445.AM2012-5389
Abstract 5392: Angiocidin induces differentiation of acute myeloid leukemia (AML) cells
Authors: Tuszynski George P. , Rothman Vicki 
Published: August 2012

Abstract
Acute myeloid leukemia (AML) is a malignant proliferative disorder where blast stage cells fail to terminally differentiate and accumulate in the blood and bone marrow. AML represents a very significant health risk in the general population with rising incidence in aging adults. From 2004-2008 the median age at diagnosis was 67.8 years and it is estimated 12,950 adults will be diagnosed with 9,050 deaths from AML leukemia in 2011 (http://seer.cancer.gov/statfacts/html/amyl.html, accessed November 2011). Standard AML therapy requires intensive combination chemotherapy with a low rate of durable remissions often requiring stem cell transplantation and associated with significant treatment-related toxicity, especially in elderly patients. Due to this toxicity, the majority of elderly patients are not eligible for therapy. Therefore, new therapeutic options for the treatment of AML are urgently needed. In this study, we present evidence that the human protein angiocidin, discovered in our laboratory, has the potential to be used as a novel, non-toxic therapy for AML. We found that angiocidin can induce both AML cell lines and primary patient cells to increase expression of surface markers characteristic of a more normal differentiated phenotype. We evaluated expression of CD14, a major receptor for the innate immune system in macrophages, CD54 or ICAM-1, the major adhesion receptor used by macrophages for endothelial transmigration, and CD15, a neutrophil phagocytosis receptor. Expression of these receptors was measured by flow cytometry after cells were cultured for 24 hours in media alone or media containing 10 μg/ml angiocidin. Angiocidin up-regulated these receptors by more than 10 fold in 50% of the AML cells tested. The AML cells included the cell line THP-1 and 11 primary AML patient cells. Angiocidin up-regulated CD14 and CD54 in THP-1 cells and in 3 out of 5 M5 phenotype AML patient cells tested and 1 M4 AML phenotype out of 6 M4 samples tested. Angiocidin also up-regulated CD15 in 1 M4 AML patient phenotype out of 6 M4 patient cells tested. These results suggest that angiocidin can differentiate AML cells and therefore has the potential to be developed as differentiation therapy for AML.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5392. doi:1538-7445.AM2012-5392
Abstract 54: Cancer-associated fibroblasts induce epithelial-mesenchymal-transition and stemness in non-small-cell lung cancer
Authors: Shintani Yasushi , Abulaiti Abulimiti , Kimura Toru , Nakagiri Tomoyuki , Inoue Masayoshi , Sawabata Noriyoshi , Minami Masato , Okumura Menoshin 
Published: August 2012

Abstract
The tumor microenvironment is composed of different types of stromal cells and a key component of tumor progression. It has been hypothesized that these stromal components are functionally organized to promote the survival of cancer cells. A specific subset of stromal cells, termed cancer-associated fibroblasts (CAFs), secretes factors that promote tumorigensis. To investigate whether CAFs constitute a specific microenvironment conductive for lung cancer progression, we performed in vitro and in vivo experiments using CAFs derived from primary lung cancer in conjunction with the human lung adenocaricinoma cell lines. We first showed that conditioned medium (CM) from human CAFs was biologically active. When human lung adenocarcinoma cell lines (A549 and NCI-H358) were cultured with CM from CAFs, epithelial cells became spindle and scattered as well as decreased cell surface E-cadherin. Further CM increased N-cadherin and vimentin expression, which is a hallmark of an epithelial-mesenchymal-transition (EMT). Coculture experiments using traswell plates with inserts of pore size 3 μm also showed EMT change in cancer cells. CM led cancer cells to enhance expression of stem cell markers such as CD44 and CD133 mRNA levels by ten times. It also triggered the acquisitions of cancer stemness such the ability of resistance to cisplatin or gefitinib as well as sphere formation. These phenotype changes associated with EMT and stemness were inhibited by the addition of TGF-β inhibitor, SB431542 (10 μM). The s.c. coinjection of human lung adenocarcinoma cell lines and human CAFs to the mice result in a high rate of tumor formation compared with the injection of these cell lines without CAFs. A decreased expression of epithelial markers and upregulation of angiogenesis and proliferative index were detected in specimens from mice with coinjection of these cells. TGF β inhibitor attenuated the tumor formation enhanced by coinjection with CAFs. The compound was injected i.p. at 0.2 mg/kg (1 per day, 5 per week for 2 weeks) after coinjection. These results indicate that the paracrine interplay between CAFs and cancer cells mediated by TGF-β signaling leads to an EMT driven gain of cancer stem cell properties and suggest that the CAFs contribute a specific niche for tumor progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 54. doi:1538-7445.AM2012-54
Abstract 5477: Ambient exposure to air pollutants and risk of neuroblastoma
Authors: Heck Julia E. , Wilhelm Michelle , Lombardi Christina , Cockburn Myles , Ritz Beate 
Published: August 2012

Abstract
Background: Some reports have linked neuroblastoma to parental occupational exposure to hydrocarbons and other chemicals. Our aim was to assess the association between neuroblastoma and exposure in pregnancy and early life to criteria air pollutants (CO, O3, PM10, PM2.5, and NOx) and to certain air toxics which are established or suspected carcinogens (benzene, 1,3 butadiene, PAHs, xylenes, carbon tetrachloride, and others). Of the criteria air pollutants, CO and NOx arise primarily from motor vehicle exhaust and thus best represent traffic-related pollution, while O3 and PM arise from a variety of sources and should be considered as markers of regionally distributed background air pollution. Methods: The Air Pollution and Childhood Cancers study ascertained all cancers diagnosed 1988-2007 in the California Cancer Registry among children less than 6 years of age; we were able to match 89% to a California birth certificate. Controls were frequency-matched by year of birth and selected at random from California birthrolls. The final analysis included 1073 neuroblastoma cases and 209,700 controls. Home addresses, as listed on birth certificates, were geocoded and linked to the nearest California Air Resources Board air pollution monitor. For those living within 5 miles of an air pollution monitor, average measurements of criteria air pollutants and air toxics were determined for each trimester of pregnancy and for the first year of life. Multivariate regression models were used to assess the relation between air pollutants and neuroblastoma, with adjustment for maternal race, socioeconomic status, and birth year. Odds ratios compare children in the highest quartile of exposure to those in the lowest exposure group. Results: Exposure to ozone in the 1st (OR =1.27, 95% CI 1.01, 1.60) and 2nd (OR=1.30, 95% CI 1.02, 1.64) trimesters was associated with an increased risk of neuroblastoma (n cases=565 within 5 miles of a monitor). Neuroblastoma was also associated with exposure to carbon tetrachloride in the first trimester (OR=2.62, 95% CI 1.06, 6.46), although this result was based upon 60 cases living within 5 miles of an air toxics monitor. We found no evidence of associations between neuroblastoma and other criteria air pollutants nor other air toxics, including no evidence of associations with traffic-related pollution. Conclusions: This is the first study to suggest a relation between neuroblastoma and ambient levels of air pollution.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5477. doi:1538-7445.AM2012-5477
Abstract 5480: Consumption of Lake Ontario sport fish and the incidence of melanoma in the New York State Angler Cohort Study (NYSACS)
Authors: Green Joseph W. , Swanson Mya K. , Olson James R. , Bonner Matthew R. 
Published: August 2012

Abstract
Exposure to polychlorinated biphenyls (PCBs) and other persistent organic pollutants (e.g., toxaphene) has been linked to an increased risk for melanoma in occupational settings. Great Lakes fish bioaccumulate PCBs and organochlorine pesticides, thus consumption is thought to be an important non-occupational exposure route. We investigated the consumption of sport-caught fish from Lake Ontario and the incidence of melanoma in the New York State Angler Cohort Study (NYSACS), a prospective cohort of 17,097 anglers and their spouses aged 18 to 40 years old at enrollment. Participants completed a mailed self-administered questionnaire upon enrollment in 1991. The questionnaire queried for the number of years that fish from L. Ontario were consumed, frequency of species specific fish consumption as well as demographic factors, smoking history and other selected potential confounders. As of December 31, 2008, fifty-one histologically confirmed, first primary, incident melanoma cases were identified via the New York State Cancer Registry. Vital status was determined by linkage with the Social Security Administration Death file. Prevalent cancer cases (n = 196) were excluded. Of the remaining 16,901cohort members, 10% (n=1,672) were lost to follow-up and censored in the year they left New York State. Analyses were restricted to Caucasians (n= 16,326). Fish consumption was dichotomized into never vs. ever. Duration of consumption was categorized into tertiles based on the distribution among the cases reporting eating Lake Ontario sport-caught fish. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals, adjusting for age, income, years of education and number of years fishing in New York State. Lake Ontario sport-caught fish consumption was weakly associated with melanoma risk RR=1.33(0.6-2.99) as compared with non-consumers. Duration of Lake Ontario fish consumption was not convincingly associated with melanoma incidence (non-eaters RR = 1.0 (ref); 1st tertile RR = 1.07 (95% CI = 0.38-3.06); 2nd tertile RR = 1.41 (95% CI = 0.49-4.03); 3rd tertile RR = 2.16 (95% CI = 0.79-5.89); p-for trend =0.10. Although interpretation of our preliminary results is complicated by a small number of cases (n=52) and inability to control for potential confounding from sun exposure, they suggest that consumption of Great Lakes fish contaminated with PCBs and other organochlorine compounds was not associated with incidence of melanoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5480. doi:1538-7445.AM2012-5480