bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5591: Detection of autoantibody responses to prostate cancer-associated antigens following treatment of patients with androgen deprivation therapy
Authors: Maricque Brett B. , McNeel Douglas G. 
Published: February 2011

Abstract
Over the last decade, immunotherapies have been developed for the treatment of prostate cancer with the goal of generating anti-tumor immune responses. Vaccine-based treatments target the immune system to a specific antigen, or set of antigens, expressed by the tumor. Other therapeutic modalities, including androgen deprivation therapy, can result in tissue damage and have been demonstrated to elicit prostate antigen-specific immune responses. The evaluation of immune responses to individual tumor antigens in the context of these non-antigen-specific immunomodulatory treatments has been notoriously difficult and time-consuming. We have previously reported a panel of 125 commonly recognized prostate cancer-associated antigens identified from multiple IgG screening approaches. This panel included multiple cancer-testis antigens and antigenic proteins recognized by IgG in patients with chronic prostatitis or prostate cancer. In the current study we questioned whether this panel could be used to identify antigen-specific immune responses elicited in patients with prostate cancer following androgen deprivation. 125 lambda phage encoding these unique antigens were spotted in triplicate using a high-throughput, high-density SEREX methodology. Sera were obtained from 33 patients with prostate cancer collected pretreatment and three months post-androgen deprivation therapy. These sera were used to probe this panel and IgG antibody responses were detected and objectively quantified by densitometry. 31 sera sets met pre-specified criteria as adequate for analysis. Results demonstrated that autoantibodies were induced to 62 of the 125 antigens. IgG responses were elicited to 21 of the antigens in multiple patients, including MAD-Pro-34, MAD-CT-1, and LAGE-1, each of which have previously been demonstrated to be the targets of autoantibody responses in prostate cancer patients. IgG responses were detected to at least one protein in 18 of 31 patients, and to multiple antigens in 11 of 31 patients. These data demonstrate that androgen deprivation elicits IgG responses to prostate-associated proteins, and that responses can be detected using a panel of commonly recognized prostate antigens. Further studies will aim to characterize this panel and autoantibody profiles in patients treated with other non-antigen-specific immunotherapies or anti-prostate tumor 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 5591.
Abstract 5593: A combination of HDAC inhibitor Entinostat (MS-275), All Trans Retinoic Acid (ATRA) and low dose Doxorubicin causes regression of established xenografts of triple negative breast cancer
Authors: Nguyen Nguyen K. , Korangath Preethi , Sabnis Gauri , Brodie Angela , Ordentlich Peter , Stearns Vered , Sukumar Saraswati 
Published: February 2011

Abstract
Triple negative breast cancer (TNBC) is a subgroup of breast cancer that rapidly develops resistance to chemotherapy. Currently, TNBC patients are treated with anthracycline and taxane-based regimens. These treatments result in some improvements in the clinical outcomes; however, they are associated with poor prognosis. Also, endocrine therapies are ineffective since the tumors do not express the estrogen receptor. Recent studies have shown that histone deacetylase (HDAC) inhibitors could reverse the epigenetic profile of some genes, including ER, EGFR, and RARβ2. We have recently shown that treatments that combine the HDAC inhibitor, Entinostat (MS-275), with the aromatase inhibitor, Letrozole, result in regression of xenografts of MDA-MB-231 breast cancer cells. Since RARβ2 is re-expressed as well, we reasoned that combining epigenetic therapy using MS-275, with differentiation therapy using a RARβ2 agonist (ATRA) will provide an effective combination of drugs against TNBC. We also examined possible potentiation of anticancer activity of these agents by low nontoxic doses of chemotherapy (doxorubicin). In vitro, human TNBC cell lines, MDA-MB-231, HCC1954, HCC 1143, and BT20 responded significantly better to the triple combination compared to the drugs used singly or in combination with MS-275. Upon treatment, re-expression of the silenced RARβ2 and downstream effectors was observed in the cell lines in vitro and in tumor xenografts of MDA-MB-231 cells. Subcutaneous tumor growth in immunodeficient mice was strongly inhibited (10/14 significant regression) using a combination of MS-275, ATRA and low dose Doxorubicin, compared to the drugs administered singly or in combination with MS-275. No significant weight loss was observed in any of the groups. These results suggest that combination of HDAC inhibitor and RARβ2 agonist with low dose chemotherapy has the potential to be an effective treatment against TNBC. This study provides encouraging new information for a nontoxic, and novel combination of drugs which could be effective against TNBC.
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 5593.
Abstract 5597: NK cells and CD8+ T cells in orthotopic pancreatic cancer model: Mediation of anti-cancer immune response by 5-fluorouracil and interferon-α
Authors: Khallouf Hadeel , Serba Susanne , Märten Angela , Jäger Dirk , Schmidt Jan 
Published: February 2011

Abstract
Pancreatic cancer has the poorest prognosis of all cancers urging the necessity of new therapeutic approaches. Recent clinical data show encouraging results for combining Interferon-α (IFN-α) immunotherapy with 5-Fluorouacil (5-FU) chemotherapy. However, the role of IFN-α in this immunochemotherapy scheme is still elusive. Here we investigate in vivo the relevance of different immune subpopulations in the anti-cancer immune response mediated by IFN-α in combination with 5-FU.
Luciferase-transfected Panc02 cells were implanted in the pancreas of C57BL/6 mice. Five days later, mice were treated with 5-FU alone, 5-FU + IFN-α or with a vehicle control. In parallel, CD4+ T cells, CD8+ T cells, and NK cells were depleted by neutralizing antibodies. Depletion of CD11c+ dendritic cells (DCs) was performed using transgenic CD11c. DTR mice. On day 21, mice were sacrificed and tumors were measured and frozen for further immunohistochemical analysis to evaluate the immune cells infiltration. NK cells were isolated and enriched from spleens of mice and their lytic activity was tested against Panc02 cells using a standard chromium release assay.
Our data show that treatment with IFN-α + 5-FU has significantly decreased tumor volume in comparison with control or 5-FU treatments. On the other hand, this decrease in tumor volume was remarkably abolished by depleting CD8+ T cells or NK cells. Furthermore, NK cells isolated from spleens of IFN-α + 5-FU treated mice showed enhanced cytotoxicity towards pancreatic cancer cells (Panc02). Meanwhile, studying the role of CD4+ T cells and DCs besides immunohistochemical analysis is still ongoing. To conclude, this study gives more insight about the mechanism of action of INF-α in combination with 5-FU and introduces CD8+ T cells and NK cells as main players in the observed anti-cancer 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 5597.
Abstract 5603: Impact of combination of PSK with TGF-beta inhibitor on anti-tumor immunity
Authors: Hiroaki Tanaka , Yamazoe Sadaaki , Iwauchi Takehiko , Muguruma Kazuya , Kubo Naoshi , Kato Yukihiro , Morimoto Junya , Kashiwagi Shinichiro , Fuyuhiro Yuhiko , Noda Eiji , Amano Ryosuke , Inoue Toru , Yamada Nobuya , Maeda Kiyoshi , Ohira Masaichi , Hirakawa Kosei 
Published: February 2011

Abstract
The transforming growth factor-β (TGF-β) has a role in tumor progression and metastasis. Secretion of TGF-β by tumor cells also suppresses an antitumor immune response in which dendritic cells (DCs) play an important role to activate cytotoxic T lymphocytes (CTLs). Here we report that small molecule TGF-β signaling inhibitor, SB-431542 (SB), induce DC maturation in vitro when combined with Protein-bound polysaccharide K (PSK). PSK has been used clinically as an anti-tumor agent in Japan. It has been reported that PSK have potential to induce anti-tumor immune response. In this study, we examined the impact of PSK and SB-431542 on maturation of DCs under immunological tolerant status. At first, we added SB and PSK to cultures of human DCs generated from peripheral monocytes in the presence of TGF-β and examined expression of CD83, production of Interleukin-12 (IL-12) and capacity of DCs to induce T cell proliferation. SB-431542 with PSK induced upregulation of CD83 of human DCs and improved their abilities to produce interleukin 12. They also augmented capacity of human DCs to activate naïve T cells in allogeneic mixed lymphocyte reaction. These results suggested that TGF-β receptor I kinase inhibitor such as SB-431542 should be able to induce antitumor immune response in immuno-tolerant patients associated with TGF-β activity.
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 5603.
Abstract 5604: Modulation of Stat3 in the tumor microenvironment enhances adoptive T cell therapy
Authors: Kujawski Maciej , Zhang Chunyan , Herrmann Andreas , Reckamp Karen L. , Scuto Anna , Jensen Michael , Figlin Robert , Yu Hua 
Published: February 2011

Abstract
Adoptive T cell transfer has shown promise in several malignancies. However, the need to expand antigen-specific T cells for prolonged periods ex vivo and the immunosuppressive effects of the tumor microenvironment severely limit its antitumor efficacy. To overcome these challenges, we tested the feasibility of stimulating and expanding transferred T cells in vivo by targeting Stat3, an oncogenic transcription factor critical for mediating tumor immunosuppression. In contrast to Stat3+/+ CD8+ T cells, transferred naïve CD8+ T cells with genetic Stat3 inhibition, effectively infiltrated tumors where they proliferated robustly, resulting in increased tumor antigen-specific CD8+ T cell activity and tumor growth inhibition. To facilitate the clinical translation of these findings, we further tested sunitinib, an FDA-approved tyrosine kinase inhibitor that has been shown to block Stat3 in several cell types. Sunitinib treatment combined with adoptive T cell transfer of Stat3−/− CD8+ T cells resulted in significant tumor growth inhibition in both immunosuppressed and immunocompetent hosts. Furthermore, sunitinib enhanced tumor T cell infiltration, dendritic cell activation and decreased tumor conversion of T regulatory cells. Targeting Stat3 in tumor cells and immune cells with sunitinib represents a novel approach to overcoming the obstacles that currently face adoptive T cell transfer therapy, which can be translated for immediate use in the clinic for treating cancer.
Supported by R01CA146092-01, K12 CA 01727, Kure It Kidney Cancer Research Fund and the Richard and Nancy Bloch Research Fund.
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 5604.
Abstract 5615: Effects of corticosteroids on tumor immunity induced by anti-CTLA-4 mAb therapy in a mouse model
Authors: Maeda Yuka , Kato Takuma , Wang Linan , Muraoka Daisuke , Sato Eiichi , Wolchok Jedd D. , Old Lloyd J. , Shiku Hiroshi , Nishikawa Hiroyoshi 
Published: February 2011

Abstract
Blockade of CTLA-4 activates/augments CD4+ and CD8+ tumor-specific T cell responses and results in tumor rejection. However, concomitant immune related adverse events (irAEs) in some anti-CTLA-4 mAb treated patients, such as skin rash and gastrointestinal inflammation, suggest that the breaking of tolerance to some normal self-antigens may accompany anti-tumor responses. As a consequence, patients are treated with immunosuppressive drugs, such as corticosteroids. Surprisingly, corticosteroids have not been reported to affect the anti-tumor responses induced by anti-CTLA-4 mAb; indeed, complete and enduring tumor regression has been seen in patients treated for irAEs with various immunosuppressive medications. In this study, we investigated the impact of corticosteroids on anti-tumor immune responses elicited by anti-CTLA-4 mAb in BALB/c mice bearing CMS5a-NY-ESO-1, a transplantable fibrosarcoma expressing NY-ESO-1 (an extensively studied human cancer/testis antigen). After CMS5a-NY-ESO-1 tumor inoculation, graded doses of methylprednisolone injection were initiated. Low doses of corticosteroids, similar to those used to treat patients with irAEs, did not suppress anti-tumor effects of anti-CTLA-4 mAb. However, high doses of corticosteroids, exceeding those used to treat patients with irAEs, impaired tumor growth inhibition by anti-CTLA-4 mAb. Furthermore, when high doses of corticosteroids were injected after the complete regression of tumors, approximately 30% of mice exhibited recurrence of CMS5a-NY-ESO-1 tumors at the initial tumor inoculation sites. This was associated with suppression of CD4+ and CD8+ T cell responses, indicating that anti-CTLA-4 mAb treatment induced an equilibrium-state of anti-tumor immunity, but not tumor eradication in these mice. Analyses of NY-ESO-1-specific CD4+ and CD8+ T cell responses in these mice showed that corticosteroids decreased the number of NY-ESO-1 specific T cells. We propose that dose and timing are important considerations for use of immunosuppression to treat irAEs of CTLA-4 blockade.
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 5615.
Abstract 5617: Enhancement of antitumor radiation efficacy and the abscopal effect by ECI301 mediated TLR4 dependent innate immunity in mice
Authors: Shiraishi Kenshiro , Yokochi Shoji , Ishiwata Yoshiro , Ishihara Mariko , Nakagawa Keiichi , Matsushima Kouji 
Published: February 2011

Abstract
[Background] We have previously demonstrated that ECI301, a variant form of human MIP-1α, induced marked inhibition of tumor growth at the irradiated site, with complete tumor eradication and consistent induction of prevention of tumor growth at a non-irradiated site, designated as an abscopal effect (Clin Cancer Res. 2008;14(4):1159-66). This abscopal effect was tumor type independent. In current study, we further studied the action of ECI301 using C3H/HeN, C3H/HeJ and athymic mice implanted with tumor cells. Using RT-PCR analysis, we had found that high mobility group box 1 (HMGB1) RNA level, an important mediator of local and systemic inflammation was up-regulated by ECI301 in tumor tissue. So we also carried out anti-HMGB1 antibody treatment in tumor-bearing mice with ECI301 and radiation.
[Methods] FM3A cells were subcutaneously implanted in the both flanks of C3H/HeN and C3H/HeJ mice. When tumor size reached approximately 10 mm in diameter, local irradiation (6 Gy) was delivered from just above the right tumor and ECI301 was administrated as a single dose intravenously once a day for 5 consecutive days, beginning at day 1 after irradiation. Athymic nude mice bearing subcutaneous colon26 tumor cells were treated with local irradiation and ECI301 was administrated as the same manner.
[Results] ECI301 inhibited the tumor growth not only in the right flank but also in the left flank (non-irradiation site) in C3H/HeN mice implanted with FM3A cells. In C3H/HeJ mice, however, ECI301 did not enhance the effect of irradiation on the tumor in both flanks. In C3H/HeN study, HMGB1 RNA level was up-regulated in both sides of tumor. Moreover, anti-HMGB1 antibody treatment eliminated the anti-tumor effect of ECI301 in both sides. Furthermore, ECI301 did not inhibit the tumor growth in athymic mice implanted with colon26 cells.
These results suggest that the ECI301-induced abscopal effect may be exerted via TLR4 and depend on the activation of T cells, and indicates that the effect of ECI301 may be promoted via inflammation in irradiated tumor tissue with HMGB1-dependent mechanism. [Conclusion] Ionizing radiation induces inflammation and immune response in irradiated tumor tissue. This immunological mechanism is greatly enhanced by ECI301, resulting in the abscopal effect that is essentially intriguing for clinical setting. Our data will encourage future therapeutic application of ECI301 in the treatment of advanced or metastatic cancer with radiation 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 5617.
Abstract 562: Stromal TLR4 and IL 6 expression as potential prognostic inflammation-associated markers for colo-rectal cancer progression
Authors: Cammarota Rosaria , Bertolini Valentina , Pennesi Giuseppina , Bucci Eraldo O. , Garlanda Cecilia , Barberis Massimo C. , Sessa Fausto , Laghi Luigi , Noonan Douglas M. , Albini Adriana 
Published: February 2011

Abstract
Epidemiological studies suggest that chronic inflammatory conditions constitute pre-neoplastic conditions.
To study how chronic inflammation could affect tumor growth and progression, we quantified the presence of inflammatory cells and expression of inflammatory cytokines by immunohistochemistry on archival tissue samples from 116 patients. We considered 13 cases of ulcerative colitis, 34 tubular or tubulo-villous adenomas with low or high grade dysplasia, and 53 infiltrating adenocarcinomas with T1, T2, T3, and T4 staging. Sixteen specimens of healthy mucosa resected along with the cancerous tissue were used as controls. We investigated expression of CD68 (macrophages), CD15 (neutrophils), CD31 (endothelial cells), Interleukin 6 (IL-6), Hepatocyte Growth Factor (HGF), and Toll-Like Receptor 4 (TLR-4). We considered 3 specific tissue compartments: epithelial, stromal and endothelial (vessel associated). Statistical differences between individual cell groups were determined using an unpaired two way t-test (Mann-Whitney).
Progression from healthy tissue to ulcerative colitis was characterized by a massive inflammatory-angiogenic reaction, as for a significant increase in expression of inflammation markers, paralleled by down-regulation of a potential suppressive molecule, HGF. Subsequently, a progressive increase in cells expressing CD68, CD15, TLR-4, and IL6 were found in the passage from adenoma to adenocarcinoma.
Adenocarcinoma patients that expressed high levels of TLR-4 in the stromal compartment had a significantly increased risk of relapse within 40 months. Moreover, in the subgroup of adenocarcinoma patients with a diagnosis of pT3 colon cancer (the most frequent pT), those with higher levels of TLR-4 in the tumor stroma showed increased risk for a relapse within 15 months.
These data suggest that inflammation correlates with progression in colorectal cancer, and that TLR-4 represents a potential prognostic marker of colo-rectal cancer progression.
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 562.
Abstract 5622: Development of an experimental model to test cellular therapy in combination with cytokines as a novel treatment for ovarian cancer
Authors: Ingersoll Susan Blaydes , Ahmad Sarfraz , Patel Sheylan , Ahmed Ahad , Edwards John R. , Finkler Neil J. , Holloway Robert W. 
Published: February 2011

Abstract
Because current therapies for ovarian cancer have little impact on long-term survival, there is a compelling need to develop innovative treatment strategies. Our aim was to develop in vitro and in vivo models to test cellular therapy in combination with cytokines or chemotherapies to elicit a graft versus tumor response to treat refractory ovarian cancer patients. SKOV-3 ovarian cancer cells, which were transfected with Red Fluorescent Protein (SKOV3-RFP) were passaged through nude mice to create more tumorigenic sub-lines. Two sub-lines were established, SKOV3-AF1 and SKOV3-AF2, which showed increased tumorigenicity compared to parental SKOV3-RFP cells. Both lines resulted in 100% tumor incidence in 6-8 weeks at a dose of 1 × 106 cells compared to 67% tumor incidence at 14 weeks at a dose of 5 × 106 SKOV3-RFP cells. SKOV3-AF1 and -AF2 cells were assayed to determine if peripheral blood mononuclear cells (PBMC) in combination with the cytokines IL-2 and IFNα-2b elicited a cytotoxic effect against the ovarian cancer cells. SKOV3-AF1 and-AF2 sub-lines were highly sensitive to cytotoxicity (up to 70%) mediated by PBMC (20:1 PBMC: SKOV3) in combination with IL-2 (25 ng/ml) and IFNα-2b (500 U/ml). The SKOV3-AF1 and -AF2 cells showed an average of 25% increased cytoxicity compared to parental SKOV3-RFP cells (p&lt;0.05, n=3). Interestingly, SKOV3-AF1 and -AF2 were more resistant to IFNα-2b compared to SKOV3-RFP when cultured in the presence of IFNα-2b alone. In addition, gene expression of E-cadherin and Cysteine-rich 61 (CCN1), which have been shown to play a role in the patho-biology of ovarian cancer, was assessed in SKOV3-RFP, -AF1, and -AF2 cells as well as solid tumors harvested from mice. All SKOV3-derived lines and solid tumor expressed E-cadherin by RT-PCR. None of the SKOV3-derived lines expressed CCN1; however, one of the two SKOV3-AF1 solid tumors tested expressed CCN1. Both SKOV3-AF2 solid tumors evaluated showed weak expression of CCN1. The SKOV3-derived sub-lines that we developed will be a better model to test novel ovarian cancer treatment regimens because these lines were found to be more susceptible to PBMC-mediated cytotoxicity, exhibit increased resistance to IFNα-2b, are more tumorigenic in a xenograph model, and tumors harvested from these lines express genes that make these tumors more aggressive. Collectively, these results suggest that cytokine enhanced cellular therapy may be a viable treatment option for ovarian cancer patients.
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 5622.