bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2553: Pritumumab, a natural human IgG antibody defines a tumor-associated biomarker useful in treating brain cancer patients
Authors: Glassy Mark C. , Gupta Rishab 
Published: May 2015

Abstract
Pritumumab is a natural human IgG1 kappa antibody that has been derived from a B-cell isolated from a regional draining lymph node of a patient with cervical carcinoma. Specificity analysis of the antibody with human tissues showed the target antigen, altered tumor-associated vimentin, to be highly restricted to various epithelial cancers and not normal cells and tissues. Daunomycin-pritumumab conjugates were generated that increased the effectiveness of the antibody. In various phase II clinical trials in Japan 249 patients with brain cancer were treated with unconjugated pritumumab. The overall response rate was between 25-30%, a 9-fold increase over standard care, with several survivors beyond 5-years post-treatment. The patients were on a low dose regimen of 1mg given twice a week for a course of 24 weeks for a total dose of 48 mgs per course. Pritumumab appears to be a safe and effective therapy in patients with brain cancer.
Citation Format: Mark C. Glassy, Rishab Gupta. Pritumumab, a natural human IgG antibody defines a tumor-associated biomarker useful in treating brain cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2553. doi:10.1158/1538-7445.AM2014-2553
Abstract 2556: The predictive role of tumor-associated macrophages in stage IIIA pN2 non-small cell lung cancer after neoadjuvant chemotherapy and surgery
Authors: Feng Po-Hao , Yu Chih-Teng , Wu Chin-Yang , Yen Tzung-Hai , Lee Kang-Yun 
Published: May 2015

Abstract
Introduction: Neoadjuvant chemotherapy improves survival in patients with pN2 stage IIIA non-small cell lung cancer (NSCLC). However, the majority relapse eventually even with mediastinal downstaging. Our study investigated the predictive role of tumor-associate macrophages (TAMs) in these patients.
Methods: Between 2005 and 2008, twenty-two pN2 stage IIIA NSCLC patients underwent cisplatin/docetaxel neoadjuvant chemotherapy and surgery were retrospectively enrolled. Immunohistochemical staining of CD68 was used to identify macrophages in stored tissues.
Results: The objective response rate was 68%, overall median disease-free survival (DFS) was 13.1 months (95% CI 6.1-20.2 months) and median overall survival (OS) 48.0 months (95% CI 24.0-72.1 months). Multiple Cox regression analysis showed mediastinal downstaging to pN0 (HR=0.039, 95% CI 0.004-0.349, p=0.004) and high total macrophage numbers (HR=1.01, 95% CI 1.002-1.017, p=0.012) were independent factors for DFS. In the 16 patients downstaged to pN0, those with low total macrophage numbers had longer DFS (median 33.4 months), compared with those with high numbers (13.4 months, p=0.037).
Conclusions: Low total macrophage numbers were also an independent factor for better DFS in pN2 stage IIIA NSCLC patients receiving neoadjuvant chemotherapy and surgical resection, which association was kept in patients downstaged to pN0. Further prospective study is warranted to confirm the predictive role of TAM in these patients.
Citation Format: Po-Hao Feng, Chih-Teng Yu, Chin-Yang Wu, Tzung-Hai Yen, Kang-Yun Lee. The predictive role of tumor-associated macrophages in stage IIIA pN2 non-small cell lung cancer after neoadjuvant chemotherapy and surgery. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2556. doi:10.1158/1538-7445.AM2014-2556
Abstract 2561: Yeast vector-encoding multiple MUC1 agonist epitopes (yeast-MUC1) can induce MUC1-specific T-cell immune responses
Authors: Tsang Kwong Y. , Boyerinas Benjamin , Jochems Caroline , Rodell Tim , King Thomas , Schlom Jeffey 
Published: May 2015

Abstract
The tumor-associated antigen MUC1 is overexpressed on various human hematological and epithelial malignancies. The MUC1 molecule, which has an N-terminal (MUC1-N) and a C-terminal (MUC1-C, which has been shown to act as an oncogene), is an attractive target for cancer immunotherapy. We have identified and reported 10 agonist epitopes (7 in the C-terminus, 2 in the N-terminus VNTR region, and 1 in the non-VNTR region) that enhance production of CD8 cytotoxic T lymphocytes. These epitopes span HLA-A2, HLA-A3, and HLA-A24 MHC class I alleles, thus encompassing the majority of the North American population. Compared to native epitopes, these agonist epitopes more efficiently generate MUC1-specific T cells, induce production of IFN-gamma by MUC1-specific T cells, and lyse human tumor cells expressing MUC1 native epitopes in an MHC-restricted manner. We have previously shown that heat-killed recombinant Saccharomyces cerevisiae yeast genetically modified to express carcinoembryonic antigen can efficiently activate human dendritic cells (DCs) and stimulate CEA-specific CD8+ T cells. Here, we investigated the ability of a Saccharomyces cerevisiae vector containing the MUC1 transgene (yeast-MUC1) and encoding MUC1 with 8 agonist epitopes to activate human DCs, stimulate MUC1-N- and MUC1-C-specific T cells, and generate MUC1-specific T cells. We show here for the first time that human DCs treated with yeast-MUC1 vectors can activate MUC1-N and MUC1-C agonist-specific T-cell lines and can act as antigen-presenting cells to generate MUC1-N- and MUC1-C-specific T cells specific to each agonist epitopes, and that these T cells are capable of lysing MUC1-expressing tumor cells. Together, these findings provide a rationale for further clinical evaluation of yeast-MUC1 constructs encoding MUC1 agonist epitopes in cancer vaccine immunotherapy.
Citation Format: Kwong Y. Tsang, Benjamin Boyerinas, Caroline Jochems, Tim Rodell, Thomas King, Jeffey Schlom. Yeast vector-encoding multiple MUC1 agonist epitopes (yeast-MUC1) can induce MUC1-specific T-cell immune responses. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2561. doi:10.1158/1538-7445.AM2014-2561
Abstract 2589: In vitro activities of the cationic antitumoral peptide LTX-315 against human melanoma cells
Authors: Eike Liv-Marie , Yang Nannan , Rekdal Øystein , Sveinbjornsson Baldur 
Published: May 2015

Abstract
The LTX-315 peptide is a lactoferricin-derived short antitumor peptide which was designed to treat solid tumors with intra-tumoral injections through a two-stage mode of action. First, the collapse of the tumor itself, then the released DAMPs from the dying tumor cell, could induce a subsequent immune protection against recurrences and metastastis. In the present study, we investigate the mechanisms behind the killing of A375 melanoma cells by LTX-315. The peptide kills the tumor cells within a few minutes by direct plasma membrane attack, but at lower concentration internalizes- and can be associated with mitochondria, ultimately leading to a lytic cell death. We show that a fluorescence-labeled peptide was internalized and localized in cytoplasmic vacuoles and accumulated around the mitochondria with subsequent rapid lysis of cells as shown by confocal live cell imaging and transmission electron microscopy. Furthermore we detected the secretion of DAMPs into the extracellular compartment minutes after peptide exposure using ELISA assay, ATP luciferase assay and western blot. Taken together, these findings suggest that LTX-315 has the ability to cause immunogenic cell death in cancer cells, and thus might have a potential as an in situ therapeutic vaccination agent
Citation Format: Liv-Marie Eike, Nannan Yang, Øystein Rekdal, Baldur Sveinbjornsson. In vitro activities of the cationic antitumoral peptide LTX-315 against human melanoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2589. doi:10.1158/1538-7445.AM2014-2589
Abstract 2590: Oral combined therapy with probiotics and alloantigen induces B cell dependent long lasting specific tolerance
Authors: Mercadante Ana Carolina T. , Perobelli Suelen , Alves Ana Paula G. , Gonçalves-Silva Triciana , Mello Wallace , Gomes-Santos Ana C , Miyoshi Anderson , Faria Ana Maria C. , Bonomo Adriana 
Published: May 2015

Abstract
Background. Allogeneic hematopietic stem cell transplantation (aHSCT) is widely used for the treatment of hematologic malignancies. Although aHSCT provides a good response against the malignant cells (GVL), it also leads to the development of graft-versus-host disease (GVHD), a severe disease with high mortality and morbidity rates. Therapy for GVHD is commonly based on non-specific immunosupression of the transplanted recipient, resulting in the concomitant inhibition of the GVL effect. Material and Methods. Here we propose an alternative approach to specifically suppress GVHD, while sparing the GVL, based on oral treatment of transplant donors with recipient antigens, associated with the intake of probiotic Lactococcus lactis as tolerogenic adjuvant (combined therapy). Results. We show that treatment of C57Bl/6 donor mice with combined therapy before the transplant protects the recipients F1 (C57Bl/6XBAL/c) mice from clinical and pathological manifestations of disease, resulting in 100% survival rate. Importantly, the animals keep the immunological competence maintaining the GVL response as well as the response to third party antigens. The protection is specific, long lasting and dependent on donor IL-10 sufficient B cells activity which induces regulatory T cells in the host. Conclusion. These data suggest that combined therapy is a promising strategy for prevention of GVHD with preservation of GVL, opening new possibilities to treat human patients subjected transplantation.
Note: This abstract was not presented at the meeting.
Citation Format: Ana Carolina T. Mercadante, Suelen Perobelli, Ana Paula G. Alves, Triciana Gonçalves-Silva, Wallace Mello, Ana C Gomes-Santos, Anderson Miyoshi, Ana Maria C. Faria, Adriana Bonomo. Oral combined therapy with probiotics and alloantigen induces B cell dependent long lasting specific tolerance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2590. doi:10.1158/1538-7445.AM2014-2590
Abstract 260: Integrative genomic analysis identifies epigenetic marks that mediate genetic risk for epithelial ovarian cancer
Authors: Koestler Devin C. , Chalise Prabhakar , Cicek Mine S. , Cunningham Julie M. , Armasu Sebastian , Larson Melissa C. , Chien Jeremy , Block Matthew , Kalli Kimberly R. , Sellers Thomas A. , Goode Ellen L. , Fridley Brooke L. 
Published: May 2015

Abstract
Both genetic and epigenetic factors influence the development and progression of epithelial ovarian cancer (EOC). However, there is an incomplete understanding of the interrelationship between these factors and whether they interact to impact disease risk. Given that the development of ovarian cancer is complex, we aimed to identify DNA methylation marks that are candidates for mediating ovarian cancer genetic risk. We used 214 cases and 214 age-matched controls from the Mayo Clinic Ovarian Cancer Study. Pretreatment, blood-derived DNA was profiled for genome-wide methylation (Illumina Infinium HumanMethylation27 BeadArray) and single nucleotide polymorphisms (SNPs, Illumina Infinium HD Human610-Quad BeadArray). We employed a three-step filtering procedure, followed by the Causal Inference Test (CIT), to distinguish CpG sites that mediate genetic risk, from those that are consequential or independently acted on by genotype. Controlling for the estimated distribution of immune cells and other key covariates, we identified 1,993 out of 25,926 (7.7%) CpGs that were significantly differentially methylated between cases and controls (FDR, q &lt; 0.05). The relationship between methylation and case-control status among these 1,993 CpGs was found to be highly consistent with the results of an independent study. Implementation of the CIT test revealed 13 CpG/SNP pairs, comprising 13 unique CpGs and 17 unique SNPs, which represent potential methylation-mediated relationships between genotype and EOC risk. These findings provide additional insight into EOC etiology and may serve as novel biomarkers for EOC susceptibility.
Citation Format: Devin C. Koestler, Prabhakar Chalise, Mine S. Cicek, Julie M. Cunningham, Sebastian Armasu, Melissa C. Larson, Jeremy Chien, Matthew Block, Kimberly R. Kalli, Thomas A. Sellers, Ellen L. Goode, Brooke L. Fridley. Integrative genomic analysis identifies epigenetic marks that mediate genetic risk for epithelial ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 260. doi:10.1158/1538-7445.AM2014-260
Abstract 2613: Wnt/β-catenin signaling mediates the anti-tumor activity of three ginsenoside derivatives in lung cancer
Authors: Bi Xiuli 
Published: May 2015

Abstract
In previous publication, the anti-tumor activity of 25-hydroxyprotopanaxadiol (25-OH-PPD), a natural compound isolated from fruits of Panax ginseng, has been studied. In the current study, we investigated the anti-tumor activity of three derivatives synthesized from 25-OH-PPD, namely xl, 1c, and 8b, respectively. All three compounds significantly inhibited the growth of human lung cancer cells in vitro, while having lesser effect on the growth of normal primary muscle cells. In vivo, oral administration of three compounds could significantly inhibit the growth of xenograft tumors without affecting body weight. Further mechanistic study demonstrated that these compounds could decrease the expression levels of β-catenin and its downstream targets Cyclin D1, CDK4, and c-myc in A549 cells. Taken together, the results suggested that the anti-tumor activity exerted by these 25-OH-PPD derivatives is partially through β-catenin mediated signaling pathway in lung cancer cells, a finding that could potentially translate into a chemotherapeutic strategy for the treatment of lung cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Xiuli Bi. Wnt/β-catenin signaling mediates the anti-tumor activity of three ginsenoside derivatives in lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2613. doi:10.1158/1538-7445.AM2014-2613
Abstract 2634: Direct reprogramming of tumor cells: a basis for novel therapeutic approaches
Authors: Bluemel Lena , Huelsewig Carolin , Zaehres Holm , Schoeler Hans , Kiesel Ludwig , Bernemann Christof 
Published: May 2015

Abstract
Introduction
Direct reprogramming describes a process by which differentiated cells can be converted into virtually any other cell type, including terminal differentiated cells. This breakthrough offers a chance for regenerative medicine in order to treat patients suffering from degenerative diseases like Parkinson disease or tissue damages.
We believe that direct reprogramming of tumor cells provides a basis for novel targeted therapies of aggressive tumors. These tumors could be reprogrammed into tumors of another, less aggressive subtype, that could potentially be treated more easily than the parental tumor does.
We used the most aggressive breast cancer subtype - triple negative breast cancer - as research model. Its missing expression of both hormone receptors (HR) as well as HER2 renders this subtype more aggressive compared to HR or HER2 positive tumors. It also implies its poorer prognosis compared to other breast cancer subtypes, for which targeted therapies are available, e.g. anti-HER2 therapies that drastically improved formerly poor prognosis of HER2 positive cancer to a much better prognostic subtype nowadays.
We suggest that by use of direct reprogramming of triple negative breast cancer cells into HER2 positive cancer cells, these cells are susceptible to anti-HER2 targeted therapies, shifting its poor prognosis into better prognosis.
Methods
Triple negative breast cancer cell lines were transduced using HER2 expressing lentiviral particles. Molecular biological analyses were performed to investigate the functionality of the transgene. Subsequently, targeted therapies against HER2 followed by molecular analyses of effects were performed.
Results
The expression of HER2 could be shown by both mRNA (using qPCR) as well as protein (Western Blot) approaches. Additionally, immunofluorescence analysis confirmed membrane localization of HER2.
Furthermore, preliminary results using targeted anti-HER2 therapies showed reduction of proliferative capacity of formerly triple negative breast cancer cells.
Conclusion
We conclude that direct reprogramming might become a tool of converting aggressive tumor types into cells susceptible to targeted therapies. Its current system describes a proof-of-principal whether reprogramming approaches might find a way into clinical settings someday. Nevertheless, strong hurdles have to be taken to make such approaches valuable for (breast) cancer patients.
Citation Format: Lena Bluemel, Carolin Huelsewig, Holm Zaehres, Hans Schoeler, Ludwig Kiesel, Christof Bernemann. Direct reprogramming of tumor cells: a basis for novel therapeutic approaches. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2634. doi:10.1158/1538-7445.AM2014-2634
Abstract 2639: Development of immunocytotoxic RNA therapeutics for human melanoma
Authors: Lee Jaewoo , Lee Youngju , Sullenger Bruce A. 
Published: May 2015

Abstract
Pattern recognition receptors (PRRs) are a pivotal component of anti-infectious immunity, and selective induction of PRR-mediated apoptosis in cancer cells represents a novel therapeutic strategy. Retinoic acid inducible gene-I (RIG-I) is a cytoplasmic PRR that recognizes virus-associated molecular patterns, such as uncapped 5′triphosphate (5′ppp) RNA. RIG-I activation triggers innate immune response and apoptosis in infected cells, resulting in the inhibition of viral spread. Interestingly, certain cancer cells are highly sensitive to RIG-I-mediated apoptosis, and treatment with RIG-I-stimulating RNAs can selectively kill cancer cells and facilitate the induction of anti-cancer immunity. Therefore, RIG-I-stimulating RNAs may prove valuable as immunostimulatory and anti-cancer agents. Because RNAs are extremely sensitive to serum nucleases, modified RNAs have been employed to increase the stability of RNA-based therapeutics. Such modifications, however, often abrogate the immunostimulatory activity of RNAs, which hinders their development as immunostimulatory agents. Herein, we demonstrate that short single-stranded RNAs (ssRNAs) (23-93 nucleotides) with 5′ppp and stem-loop structure(s) are a potent stimulus for type I interferon (IFN) production and apoptosis of human melanoma and prostate cancer cells. 2′fluoro (2′F) modification of these 5′ppp ssRNAs not only improves serum stability, but also enhances the ability of the RNAs to induce IFNβ production and apoptosis of human cancer cells, compared to their unmodified counterparts, while 2′ O-methyl modification abrogates the anti-cancer and IFN-inducing activities of 5′ppp ssRNAs. These 5′ppp 2′F ssRNAs elicit RIG-I- and mitochondrial antiviral-signaling protein-mediated IFN production and cytotoxic effects. This study suggests that such modified RNAs may represent a novel and effective anti-cancer therapeutic.
Citation Format: Jaewoo Lee, Youngju Lee, Bruce A. Sullenger. Development of immunocytotoxic RNA therapeutics for human melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2639. doi:10.1158/1538-7445.AM2014-2639
Abstract 2658: GPEx® system to increase production of pritumumab in a CHO cell line
Authors: Bleck Gregory T. , Gupta Rishab K. , Kotlan Beatrix , York Dona , Glassy Mark C. 
Published: May 2015

Abstract
Pritumumab, a natural human IgG1 kappa antibody isolated from a lymph node of a patient with cervical carcinoma, has been used in a Phase II setting with brain cancer patients. The original human-human hybridoma secreted approximately 1 picogram of antibody per cell per day. This level of the antibody production posed cost constrains for late stage therapeutic clinical trials. To generate a more commercially viable antibody, a pritumumab-secreting Chinese hamster ovary (CHO) cell line was created using the GPEx® technology. This technology involved construction and cloning of heavy and light chain DNA. Both DNA sequences were cloned into the expression vector and transduced into HEK 293 cells that constitutively produces the MLV gag, pro, and pol. The pritumumab cell line was made by performing multiple rounds of transduction (multiplicity of &gt; 1000 retrovector particles/cell) of the GPEx® Chinese Hamster Ovary (GCHO) parental cell line with retrovector made from the gene construct developed to express the pritumumab antibody light chain (LC) and the pritumumab antibody heavy chain (HC). Five independent transductions were performed: two LC and three HC. Limiting dilution method was used to establish clonal cell lines. Top clones were selected based on pritumumab antibody titer. Pritumumab expression was determined by Protein A HPLC using a generic IgG standard. Clearly, single copies of genes were inserted efficiently in unique locations throughout the genome of the CHO cells to obtain genetically stable cell line that expressed high levels of the antibody, and represented more than a 40-fold increase in production of the antibody over the original hybridoma. Flow cytometry binding and immunohistological analyses demonstrated comparability between the recombinant form of pritumumab and the hybridoma form of the protein. Thus, high level of specific productivities and titers of the CHO clones developed through the GPEx® system will allow the therapeutic antibody program to move forward into large and extended clinical trials.
Citation Format: Gregory T. Bleck, Rishab K. Gupta, Beatrix Kotlan, Dona York, Mark C. Glassy. GPEx® system to increase production of pritumumab in a CHO cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2658. doi:10.1158/1538-7445.AM2014-2658