bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1187: Personalized cancer therapy for ovarian cancer patients.
Authors: Bravo Maria L. , Gonzalez Pamela , Kato Sumie , Garrido Marcelo , Brañes Jorge , Pizarro Javier , Barriga Maria Isabel , Leon Hector , Bustamante Eva , Alonso Catalina , Bravo Erasmo , Celis Miguel Angel , Aguilera Barbara , Barra Alejandro , Barrena Nicanor , Ibañez Carolina , Jimenez Paula , Cuello Mauricio , Owen Gareth 
Published: August 2014

Abstract
Introduction: The treatment of ovarian cancer is consists principally in radical surgery followed by chemotherapy. Patients generally respond well to first line chemotherapy (70%) but consistently relapse within 18 months, with successive rounds of chemotherapy delivering extremely low patient benefit. Despite every cancer being unique, generally all cancer patients are treated by the same chemotherapy regimes. In previous decades an approach has been to use chemosensitivity assays based on cells isolated from solid tumors to predict chemotherapy response. However, it the metastatic cancer cell (not cells in the primary tumor) that is the true target of chemotherapy. In our laboratory we have resurrected the concept of chemosensitivity but focusing exclusively on cells that have escaped the primary tumor and are potentially enriched in stem-cell like properties. Our objective was to isolate potential ovarian metastatic cells from patients and coorelate their in vitro response to the chemotherapy observed in the patient. Materials and methods: Primary cultures of ovarian cancer ascites (peritoneal fluid) were obtained with signed informed consent from a network of Chilean hospitals and potential metastatic cells cultivated. Chemotherapy response was assessed by MTS and data correlated with CA125 levels, imaging and medical criteria. Results: Analysis of 39 ovarian cancer patients with clinical follow-up demonstrated an average progression free survival of 18 months for patients predicted to respond by our assay, but only 2 months in predicted non-responders. The assay corrected identified 5 of the 6 patients who did not respond to first line carboplatin-paclitaxel therapy. Discussion: We demonstrate a clear distinction in time to relapse between patients predicted to respond in our assay as opposed to patients with no predicted clinical response, demonstrating the requirement to take this research to the stage of randomized clinical trials.
Funding BMRC CTU06 & FONDECYT 3120003 and 1120292
Citation Format: Maria L. Bravo, Pamela Gonzalez, Sumie Kato, Marcelo Garrido, Jorge Brañes, Javier Pizarro, Maria Isabel Barriga, Hector Leon, Eva Bustamante, Catalina Alonso, Erasmo Bravo, Miguel Angel Celis, Barbara Aguilera, Alejandro Barra, Nicanor Barrena, Carolina Ibañez, Paula Jimenez, Mauricio Cuello, Gareth Owen. Personalized cancer therapy for ovarian cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1187. doi:10.1158/1538-7445.AM2013-1187
Abstract 1190: Gene expression profiling identified FYN as an important gene in tamoxifen resistance and a predictor of early recurrence in patients treated with endocrine therapy .
Authors: Elias Roro Daniel , Vever Henriette , Ditzel Henrik 
Published: August 2014

Abstract
To elucidate the molecular mechanisms of tamoxifen resistance in breast cancer we performed microarray profiling and identified 366 genes with altered expression in 4 tamoxifen-resistant (TamRs) vs. the parental tamoxifen-sensitive MCF-7/S0.5 cell lines. Most of these genes were functionally linked to cell growth, proliferation, death and control of gene expression and included FYN, PRKCα, ITPR1, DPYD, DACH1, GBP1 and PRLR. Increased expression of FYN was observed in TamR cells and treatment with FYN-specific interfering RNA or a specific Src family kinase (SFK) inhibitor restored the anti-proliferative effect of tamoxifen in these cells. TamR cells also expressed increased levels of phosphorylated breast cancer antiestrogen resistance protein 1 (pBCAR1), an important downstream SFK substrate in the MAPK pathway. Evaluation of the association of subcellular localization of FYN in cancer tissue and clinical endpoints was made in 2 cohorts of ER+ breast cancer patients, one with advanced disease (N=47) and the other with early breast cancer (N=76). The result showed that plasma membrane-associated FYN expression in the cancer cells strongly correlated with longer progression-free survival compared to FYN expression not associated with the plasma membrane (p&lt;0.0002) in the advanced disease cohort. Similarly, in the early breast cancer patients, plasma membrane associated FYN expression was associated with longer metastasis-free survival (p&lt;0.003) and overall survival (p&lt;0.0005) independent of tumor size, grade and node status. Our results indicate that FYN plays an important role in tamoxifen resistance, and its subcellular location in breast tumor cells may be an important novel biomarker of response to endocrine therapy in breast cancer.
Citation Format: Daniel Elias Roro, Henriette Vever, Henrik Ditzel. Gene expression profiling identified FYN as an important gene in tamoxifen resistance and a predictor of early recurrence in patients treated with endocrine therapy . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1190. doi:10.1158/1538-7445.AM2013-1190
Abstract 1195: A molecular characterization of the anaplastic prostate carcinomas.
Authors: Aparicio Ana M. , Maity Sankar , Wang Xuemei , Hoang Anh G. , Efstathiou Eleni , Troncoso Patricia , Logothetis Christopher J. 
Published: August 2014

Abstract
Molecular markers that identify clinically meaningful, biologically based, subsets of PC are lacking. This results in inefficient clinical trial designs and suboptimal therapy selection off-protocol. The androgen receptor (AR)-negative small cell PC (SCPC) is an often-unrecognized morphological variant of the disease found on repeat biopsies during the castrate-resistant (CR) progression of PC. Its presence predicts for a poor response to hormonal therapies, a distinct clinical behavior and a short survival. Characteristic clinical features of SCPC are frequently present in patients with CRPC, constituting a clinical syndrome termed anaplastic PC. We hypothesized that the anaplastic PC share underlying biology with SCPC, irrespective of morphology. Preclinical studies show that SCPC are characterized by loss of tumor suppressors and AR signaling, as well as overexpression of mitotic genes and proneural transcription factors. To test our hypothesis we used immunohistochemistry to analyze the expression of markers in these pathways, in tumor biopsies from chemotherapy-naïve men with anaplastic PC participating in a prospective phase II clinical trial. To date we have analyzed 6 markers in 25 samples (6 with pure or mixed SCPC morphology) from prostate biopsies (n=10), transurethral resections of prostate tumors (n=4), bone marrow or bone biopsies (n=9), lymph node (n=1) or brain (n=1). Results are shown in Table 1.
Table 1. Immunohistochemistry Anaplastic PC % Positive Cells AR RB1 p53 UBE2C Ki67 CYP17A1 0 8 11 11 5 1 0 &lt; or = 10% 3 6 9 9 8 1 &gt; 10% 14 8 5 11 16 24
Of the 17 samples that had ≤10% RB1+ cells, 10 had ≤10% AR+ cells and 9 had &gt;10% UBE2C+ cells. Of the 11 samples that had ≤10% AR+ cells, 10 also had ≤10% RB1+ cells and 6 had &gt;10% UBE2C+ cells. These data support our hypothesis that the anaplastic prostate carcinomas are characterized by loss of tumor suppressors and overexpression of mitotic genes. Updated results in additional samples and of additional markers will be presented.
Citation Format: Ana M. Aparicio, Sankar Maity, Xuemei Wang, Anh G. Hoang, Eleni Efstathiou, Patricia Troncoso, Christopher J. Logothetis. A molecular characterization of the anaplastic prostate carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1195. doi:10.1158/1538-7445.AM2013-1195
Abstract 1205: Circulating micro-RNAs can detect adaptive response to therapy and aggressive subset of prostate cancer.
Authors: Aparicio Ana M. , Gallichotte Emily , Cheng Heather , Yoo Suk-Young , Maity Sankar , Logothetis Christopher , Tewari Muneesh 
Published: August 2014

Abstract
Circulating markers that inform of the adaptive biology and the clinical virulence of prostate cancer do not exist. Small cell carcinoma of the prostate (SCPC) is an aggressive, androgen receptor (AR)-negative, morphological variant that arises often during the castration-resistant progression of typical adenocarcinoma. Its presence is associated with a poor response to hormonal therapies and predicts for a short survival. Micro-RNAs (miRNAs) regulate a range of processes, including establishment and maintenance of tissue differentiation, and are well-preserved in serum. Based on the observation that SCPC are characterized by a loss of prostate epithelial marker expression (such as AR and HOXB13) and an increase in the expression of proneural transcription factors (such as MYCN and ASCL1) we formulated the hypothesis that the SCPC display a miRNA profile distinct from that of typical AR-driven prostate carcinomas. We profiled the miR extracted from the serum samples of 13 men with biopsy-proven SCPC, and of 9 men with bone-predominant metastatic CRPC. Because SCPC is associated with large tumor burdens, we selected patients with bone-predominant CRPC that had abnormally high alkaline phosphatase levels and PSA &gt; 20ng/mL. 322 miR were detected in at least one of the 22 samples. We identified two miR that were present in 10 and 11 of 13 (77% and 85%) patients with SCPC and 3 and 1 of 9 (33% and 11%) of men with unselected typical bone-predominant CRPC. Both of these miRs have been shown to control multiple genes regulating neuronal differentiation and to induce the conversion of human fibroblasts into neurons, a mechanism which may be shared by prostate adenocarcinoma cells in their transdifferentiation to small cell prostate cancer cells. Moreover, one of them was recently shown to silence AR expression. Therefore we conclude that two circulating miRs may serve to monitor adaptive responses and identify virulent subsets of prostate cancer, thus serving to guide therapy and selection of patients for clinical trials. Validation of these findings is ongoing in a larger cohort of patients.
Citation Format: Ana M. Aparicio, Emily Gallichotte, Heather Cheng, Suk-Young Yoo, Sankar Maity, Christopher Logothetis, Muneesh Tewari. Circulating micro-RNAs can detect adaptive response to therapy and aggressive subset of prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1205. doi:10.1158/1538-7445.AM2013-1205
Abstract 1232: Immunomodulatory effects of a tyrosine kinase inhibitor and vascular remodeling properties of a cancer vaccine potentiate combinatorial immunotherapy.
Authors: Donahue Renee N. , Grenga Italia , Kim Peter S. , Coplin Michael A. , Hodge James W. , Schlom Jeffrey , Farsaci Benedetto P. 
Published: August 2014

Abstract
Many tyrosine kinase inhibitors (TKIs) that have antiangiogenic proprieties have also shown to have immunomodulatory proprieties by decreasing the number and function of immunosuppressive elements such as myeloid-derived suppressor cells and T-regulatory lymphocytes. These immunomodulatory properties make TKIs attractive candidates for combination with cancer immunotherapy. The aim of this study was to investigate the differential action of vaccine and the antiangiogenic TKI sunitinib on tumor architecture, to better define the mechanisms underlying the clinical benefit of this combination. Using a CEA+ colon carcinoma mouse model in CEA-transgenic mice, we show for the first time that vaccine and TKI exert differential effects on tumor architecture. Fluorescent immunohistochemistry (IHC) of 3 distinct types of tumor vessels (identified as CD31+, CD105+, and the monocytic marker CD11b+) demonstrated that vaccine decreased monocytic vasculature while sunitinib decreased the 3 types of vasculature and fenestrations. Immunoenzymatic IHC indicated that each single treatment and the combination affected tumor compactness and tight junctions. Each single treatment decreased hypoxia, as shown by hypoxyprobe IHC analysis, while combining sunitinib with vaccine resulted in the highest tumor oxygenation. Finally, vaccine plus sunitinib increased the tumor infiltration of antigen-specific T lymphocytes. These observations suggest that vaccine acted not only as an immune stimulant, but also as an angiogenic agent. These insights will assist in rationally developing and implementing such combination therapies.
Citation Format: Renee N. Donahue, Italia Grenga, Peter S. Kim, Michael A. Coplin, James W. Hodge, Jeffrey Schlom, Benedetto P. Farsaci. Immunomodulatory effects of a tyrosine kinase inhibitor and vascular remodeling properties of a cancer vaccine potentiate combinatorial immunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1232. doi:10.1158/1538-7445.AM2013-1232
Abstract 1239: Characterization of the response of human T cells to an agonist human anti-CD27 mAb.
Authors: Sundarapandiyan Karuna , Vitale Laura , Zhao Biwei , O'Neill Thomas , Marsh Henry , Ramakrishna Venky , Keler Tibor 
Published: August 2014

Abstract
CD27, a member of the tumor necrosis factor receptor super family (TNFRSF), is constitutively expressed on the majority of mature T cells, memory B cells, and a portion of NK cells. Previously we have reported antitumor and immunological properties of the fully human anti-CD27 mAb 1F5 in huCD27 transgenic mouse models. Here we report the 1F5-induced immune modulation of isolated human T cells. In vitro activation of peripheral blood-derived T cells from different healthy volunteers with mAb 1F5 showed that crosslinking of CD27 in the presence of CD3 stimulation (OKT3 mAb) was essential to elicit proliferation and a broad spectrum of cytokine release. Analysis of this response on a multiplex cytokine array system revealed a Th1-biased cytokine profile (IFNγ, IL-2 and TNFα). Interestingly, IL-13 was the only major Th2 cytokine that was detected in large amounts. Furthermore, activation of isolated CD4+ and CD8+ T cells showed both subsets contributed to the IL-13 secretion with higher secretion amounts detected in the CD4+ T cell cultures. Altogether, the data suggest an agonistic role for 1F5 characterized predominantly by a defined antigen-receptor coupled Th1 effector response. IL-13, which appears later after stimulation may represent immune regulatory modulation as has been described in activation of the related 4-1BB co-stimulation pathway. Transcriptional profiling by microarray RNA hybridization is underway to map specific and global gene expression changes following 1F5 modulation of T cells.
Citation Format: Karuna Sundarapandiyan, Laura Vitale, Biwei Zhao, Thomas O'Neill, Henry Marsh, Venky Ramakrishna, Tibor Keler. Characterization of the response of human T cells to an agonist human anti-CD27 mAb. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1239. doi:10.1158/1538-7445.AM2013-1239
Abstract 1242: The association between treatment-related lymphopenia and survival in patients with solid tumors.
Authors: Grossman Stuart A. , Yovino Susannah , Campian Jian , Wild Aaron , Herman Joseph , Laheru Daniel , Brock Malcolm , Marur Shanthi , Balmanoukian Ani , Ye Xiaobu 
Published: August 2014

Abstract
Background: This retrospective review was conducted to determine: 1) the frequency and severity of treatment related lymphopenia (TRL) in solid tumors, 2) its association with survival accounting for prognostic variables, and 3) its relationship to radiation or chemotherapy.
Methods: Serial lymphocyte counts (pre-treatment and monthly for one year), prognostic factors, treatment details, and survival were retrospectively reviewed in 338 newly diagnosed patients with 1) high grade glioma, 2) resected pancreatic cancer, 3) unresectable pancreatic cancer, 4) stage III lung cancer, and 5) HPV- head and neck cancer in this IRB approved study. Severe TRL was defined as grade III-IV lymphopenia (&lt;500 cells/mm3).
Results: The findings in each patient cohort are similar: 1) About 40% of patients develop severe TRL two months after initiating radiation and this persists for many months, 2) There is an association between TRL at two months and shorter survival from tumor progression, and 3) The hazard ratio for reduced survival is high after adjusting for known prognostic factors. Lung cancer patients treated with neoadjuvant chemotherapy did not experience TRL until after radiation was initiated.
Conclusions: Severe TRL is common, severe, long-lasting and associated with earlier death from tumor progression in patients with solid tumors receiving radiation and chemotherapy. These studies suggest that radiation likely plays a major role in the development of TRL and that novel approaches to protect and/or restore immunologic function in patients with solid tumors are critical.
NeoplasmTotal number patientsPatients developing grade III-IV TRLMedian Survival &lt;500 vs &gt;500 lymphocytes (months)Multivariate association with reduced survival:HR, (CI), pvalueHigh grade glioma9640%13 vs 19.7 (p = 0.002)OS: 1.66, (1.05–2.64), 0.03Pancreatic resected5345%14 vs 20 (p = 0.048)OS: 2.2, (1.17–4.12), 0.01Pancreatic unresectable12074%9.2 vs 14.6 (p = 0.013)OS: 1.34, (0.09–2.0), 0.15NSCLC Stage III4750%21.8 vs 28.3 (p = 0.38)OS: 1.7, (0.8–3.6), 0.17HEENT (HPV)2236%PFS onlyPFS: 6.2, (1.1–35.2), 0.04
Citation Format: Stuart A. Grossman, Susannah Yovino, Jian Campian, Aaron Wild, Joseph Herman, Daniel Laheru, Malcolm Brock, Shanthi Marur, Ani Balmanoukian, Xiaobu Ye. The association between treatment-related lymphopenia and survival in patients with solid tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1242. doi:10.1158/1538-7445.AM2013-1242
Abstract 1247: Development of GRP78 scFv-Subtilase fusion proteins for sensitization of melanoma to chemotherapeutics.
Authors: Ray Rupa , de Ridder Gustaaf , Pizzo Salvatore V. 
Published: August 2014

Abstract
GRP78 is an important molecular chaperone in the endoplasmic reticulum (ER). However, GRP78 is aberrantly expressed on the surface of melanoma cells. Our objective is to characterize cell-surface GRP78 in melanoma and determine whether immunoconjugates against GRP78 are a viable treatment strategy. We have demonstrated that cleavage of ER GRP78 by Subtilase (SubAB), a GRP78-specific protease, sensitizes melanoma cell lines of different genotypes to melphalan, vemurafenib, and temozolomide. Our data indicate that SubAB cleavage of GRP78 sensitizes melanoma cells to melphalan and vemurafenib. We then coupled the catalytic domain of SubAB, SubA, to GRP78-single chain variable fragments derived from anti-GRP78 mouse monoclonal antibodies. We have previously published that these antibodies target GRP78+ mouse melanomas in a syngeneic mouse melanoma model. These GRP78 scFv-SubA fusion proteins are internalized by cell-surface GRP78 and the SubA moiety cleaves ER GRP78 inside the cell, leading to tumor cell sensitization to chemotherapeutics, and in some instances, tumor cell death. To determine the mechanism by which ER GRP78 cleavage sensitizes melanoma cells to chemotherapeutics, the NH2-terminal 28 kDa and COOH-terminal 50 kDa SubA cleavage products were overexpressed in melanoma cells, and pull-down experiments were performed to identify binding partners. Microarray analyses were also performed on chemotherapy-treated and GRP78 scFv-SubA fusion protein-treated melanoma cells to obtain a broad view of cellular events that occurred subsequent to ER GRP78 cleavage by SubAB or GRP78 scFv-SubA fusion proteins. These fusion proteins will then be tested in mouse melanoma models to determine whether they sensitize cancer cells to chemotherapeutics in vivo. These results of these studies may lead to the development of novel melanoma therapeutics.
Citation Format: Rupa Ray, Gustaaf de Ridder, Salvatore V. Pizzo. Development of GRP78 scFv-Subtilase fusion proteins for sensitization of melanoma to chemotherapeutics. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1247. doi:10.1158/1538-7445.AM2013-1247
Abstract 1254: Tumor infiltrating M1 macrophages work side by side with T cells to prolong the survival in patients with cervical carcinoma.
Authors: Van Der Burg Sjoerd H. , de Vos van Steenwijk Peggy , van Hall Thorbald , Jordanova Ekaterina S. 
Published: August 2014

Abstract
One of the hallmarks of cancer is the influx of myeloid cells. In this study we exploited a cohort of 86 patients with cervical carcinoma to investigate the constitution of cervical cancer infiltrating myeloid cells and their relationship to other tumor infiltrating immune cells, tumor characteristics and the survival of patients. Triple color immunofluorescent confocal microscopy was used to locate, identify and quantify macrophages (CD14), their maturation status (CD33) and their polarization (CD163). Quantification of the numbers of populations of myeloid cells based on the expression of these three markers revealed that a strong intraepithelial infiltration of CD14+ cells, more specifically the population of CD14+CD33-CD163- M1 macrophages, is associated with a large general influx of intraepithelial T lymphocytes (p=0.008) and improved survival (p=0.007) as well as forms an independent prognostic factor for survival (p=0.033). The ratio of intraepithelial CD8+ T-cells / Tregs also formed an independent prognostic factor (p=0.010). Combination of these two factors revealed a dramatic difference in survival between the group of patients whose tumor was well infiltrated with intraepithelial M1 macrophages and relatively high numbers of CD8+ T-cells compared to Tregs (100%) and the group of patients whose tumor displayed a low infiltration with M1 macrophages and a low CD8+ T-cell / Treg ratio (50%), indicating that these two populations of immune cells work side by side to improve survival. Our data suggests that reinforcement and activation of the intratumoral M1 macrophages may form an attractive immunotherapeutic option in cervical cancer.
Citation Format: Sjoerd H. Van Der Burg, Peggy de Vos van Steenwijk, Thorbald van Hall, Ekaterina S. Jordanova. Tumor infiltrating M1 macrophages work side by side with T cells to prolong the survival in patients with cervical carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1254. doi:10.1158/1538-7445.AM2013-1254