bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-163: A phase I trial investigating apoptosis induction with tumor necrosis factor or radiation alone prior to intratumoral injection of autologous dendritic cells in patients with locally advanced or low volume metastatic pancreatic cancer.
Authors: Zervos Emmanuel E. , Mule James J. , Brigham Denise , Janssen William , Cooper Jennifer , Rosemurgy Alexander S. 
Published: August 2014

Abstract
The purpose of this trial was to determine the safety, feasibility and efficacy of intra-tumoral injection of an autologous dendritic cell (DC) based vaccine following apoptosis induction with a tumor necrosis factor expressing adenovector (TNF) or low dose radiation therapy (XRT).
Methods: Between August 2006 and August 2011, 24 patients with locally advanced (n= 17) or low-volume metastatic (n=7) pancreatic cancer were enrolled to receive either: TNF on day 1 followed by vector activating XRT (2 Gy/d on days 1-3) and then an autologous, KLH pulsed DC vaccine (50M cells, day 4) for 3 weeks; or, XRT (1.9 Gy/d on days1-4) followed by DC vaccine (50M cells, day 5) for 3 weeks. Feasibility endpoints included our ability to produce the vaccine and the subject's ability to complete all phases of the protocol. Serious adverse events (SAE) were recorded to establish safety. Efficacy was established by radiographic and biochemical tumor response, progression free (PFS) and overall survival (OS).
Results: All but 2 patients completed the protocol (92%). One patient died prior to initiation of treatment (not included in survival analysis) and one disenrolled during treatment due to deep venous thrombosis. 50 of 66 (76%) total vaccines produced contained greater than 50M DC. There was no vaccine related toxicity. In the TNF group, there were 19 SAEs including one death. In the XRT group, there were 33 SAEs mostly characterized by pain, nausea, dehydration and vomiting. Two (4%) SAEs led to hospital admission, one for duodenal bleeding and one for bacteremia. Tumor response favored the radiation group as did survival. (table)
Conclusions: DC based vaccines are feasible and safe in patients with advanced pancreatic cancer. Apoptosis induction using TNF, though less complicated, imparted no survival advantage over radiation alone and may have provided some disadvantage.
Efficacy O.S. (mos) P.F.S. (mos) Stable or partial response (%) Stable or decreased Ca19-9(%) TNF (n = 15) 5.8±2.05 4.7±2.17 60 62 XRT (n = 8) 8.7±3.48 6.9±3.79 75 100 Total 6.9±2.92 5.4±2.96 65 76
Citation Format: Emmanuel E. Zervos, James J. Mule, Denise Brigham, William Janssen, Jennifer Cooper, Alexander S. Rosemurgy. A phase I trial investigating apoptosis induction with tumor necrosis factor or radiation alone prior to intratumoral injection of autologous dendritic cells in patients with locally advanced or low volume metastatic pancreatic 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 LB-163. doi:10.1158/1538-7445.AM2013-LB-163
Abstract LB-164: Treatment of advanced stage colorectal cancer with ETBX-011 immunotherapeutic.
Authors: Gabitzsch Elizabeth S. , Morse Michael A. , Lyerly H. Kim , Jones Frank 
Published: August 2014

Abstract
In this Phase 1/2a non-randomized study, 32 patients having advanced stage metastatic colorectal cancer (mCRC) were treated with a novel immunotherapeutic, ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D)). The trial included increasing doses of the agent and was found to be safe and well-tolerated at all doses assessed. There were no dropouts or treatments stopped due to adverse effects. Specific anti-CEA immune responses were observed in the majority of patients after they were treated three times over 6 weeks by subcutaneous injections of ETBX-011. Long-term follow-up in some of the patients reveled that the CEA directed immune responses persisted for up to 6-9 months after treatment and median overall-survival was 11 months. These results demonstrate that in mCRC patients the ETBX-011 immunotherapeutic generated significant CMI responses to the tolerized tumor antigen CEA. mCRC patients treated with ETBX-11 may experience extension of life and we are preparing to initiate a randomized, multicenter Phase 2b trial to further evaluate the clinical benefit.
Citation Format: Elizabeth S. Gabitzsch, Michael A. Morse, H. Kim Lyerly, Frank Jones. Treatment of advanced stage colorectal cancer with ETBX-011 immunotherapeutic. [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 LB-164. doi:10.1158/1538-7445.AM2013-LB-164
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract LB-190: Time to treatment of Latinas with breast cancer utilizing patient navigation: the Six Cities Study.
Authors: Ramirez Amelie G. , Perez-Stable Eliseo , Talavera Gregory A. , Penedo Frank J. , Carrillo J. Emilio , Fernandez Maria E. , Holden Alan E. C. , Munoz Edgar , Long-Parma Dorothy , de Mejors Sandra San Miguel , Gallion Kipling 
Published: August 2014

Abstract
BACKGROUND: Breast cancer is the leading cause of cancer deaths in Latinas. Time from cancer diagnosis to treatment initiation is critical in optimizing cancer care. Patient navigation is a potentially effective means of promoting timely treatment of breast cancer, yet efficacy is insufficiently documented. Redes en Accion here evaluates a culturally sensitive patient navigation program to reduce time from cancer to diagnosis to treatment and increase proportions of women treated within 30 days of diagnosis.
METHODS: We analyzed 109 Latinas diagnosed with breast cancer from July 2008-January 2011 (42 navigated, 67 controls). Women were navigated by locally trained navigators or non-navigated (data abstracted from charts). Kaplan-Meier, Cox proportional hazards, and logistic regression were used to determine group differences.
RESULTS: Time from cancer diagnosis to 1st treatment was lower in the navigated group (MED 21 days, control 32 days, HR 1.6, p=0.02). 64.3% began treatment within 30 days of cancer diagnosis, compared to 47.8% of non-navigated Latinas (p=0.015) controlling for stage of cancer at diagnosis and numerous characteristics of clinics and participants. Effects were due to navigator activities compared to those who did not need or utilize them, including appointment reminders, transportation arrangements, accompaniment to appointments, and translation services.
CONCLUSIONS: Patient-centered navigation to assist Latina women with breast cancer diagnoses significantly reduces time from diagnosis to treatment, and increases the proportion of women who begin treatment within 30 days of diagnosis. Improvement appears to be associated with specific navigator activities.
Acknowledgement: Redes En Acción: The National Latino Cancer Research Network (NCI U01 CA114657-05) and the Cancer Therapy and Research Center at the University of Texas Health Science at Center San Antonio (Grant # P30CA054174).
Citation Format: Amelie G. Ramirez, Eliseo Perez-Stable, Gregory A. Talavera, Frank J. Penedo, J. Emilio Carrillo, Maria E. Fernandez, Alan E. C. Holden, Edgar Munoz, Dorothy Long-Parma, Sandra San Miguel de Mejors, Kipling Gallion. Time to treatment of Latinas with breast cancer utilizing patient navigation: the Six Cities Study. [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 LB-190. doi:10.1158/1538-7445.AM2013-LB-190
Abstract LB-2: Open innovation drug discovery: A study in JQ1.
Authors: Shaw Daniel L. , Lin Charles Y. , Oakley Richard P. , Semenkovich Nicholas P. , Qi Jun , Bradner James E. 
Published: August 2014

Abstract
Collaborative research from our laboratory, in 2010, produced a first-in-class inhibitor of BET bromodomain proteins (JQ1). As an effort to promote a more open-innovation model of drug discovery, we endeavored to provide JQ1 without restriction of cost or delay to the scientific community. Toward this objective, we have optimized and completed a facile scaling synthesis capable of producing 100 g quantities of the active (+)-JQ1 stereoisomer. In the past 30 months, JQ1 has been provided to over 350 laboratories in more than a dozen countries. Through this research, BET bromodomain proteins have emerged as pharmacologically validated targets in multiple model systems of cancer including squamous carcinoma of the lung, head and neck, acute myeloid leukemia, multiple myeloma, Burkitt lymphoma, B-cell acute lymphoblastic leukemia, neuroblastoma and non-small cell lung cancer. More than 800 cancer cell lines and 25 murine models of cancer have been systematically screened with JQ1 for sensitivity to bromodomain inhibition, identifying additional therapeutic opportunities. Open availability of JQ1 has also lead to unexpected innovation outside of cancer research through studies identifying opportunities for BET bromodomain inhibition in such diverse fields as male contraception and HIV therapeutics. Since publication of the chemical structure and synthetic route to JQ1, seven new BET bromodomain inhibitors have appeared in the literature each derivatized from and/or benchmarked to the JQ1 molecule. Importantly, BET bromodomain inhibition has already accomplished clinical translation. To more objectively assess the consequence of open-innovation as a model of drug discovery, we have systematically analyzed metadata collected from published research and our ongoing efforts in compound distribution. Here, we present an interim analysis which relates the effect of open-innovation in drug discovery to the scope, productivity, reproducibility and importantly the pace of scientific research in epigenetic reader proteins. These results identify open-innovation in drug discovery as a catalyst for scientific discovery, bridging a gap between fields of research and the basic and clinical sciences.
Citation Format: Daniel L. Shaw, Charles Y. Lin, Richard P. Oakley, Nicholas P. Semenkovich, Jun Qi, James E. Bradner. Open innovation drug discovery: A study in JQ1. [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 LB-2. doi:10.1158/1538-7445.AM2013-LB-2
Abstract LB-20: Serum antioxidant levels and survival time in advanced non-small cell lung cancer patients.
Authors: Wirasorn Kosin , Hongprabhas Pranithi , Pisprasert Veeradej , Klarod Kulthida , Boonsiri Patcharee 
Published: August 2014

Abstract
Background: Oxidative stress is involved with carcinogenesis of lung cancer and promotes tumor growth. Antioxidants play roles in inhibition of oxidative stress; consequently slow progression of tumor growth. This study aimed to show the correlation between median survival in advanced-stage non-small cell lung cancer (NSCLC) patients and antioxidant levels.
Methods: Newly diagnosed advanced-stage NSCLC patient in Khonkaen University Hospital during June 2006 and June 2008 were enrolled. Participants who had history of taking dietary supplements were excluded. Tumor data and nutritional status were evaluated in all patients. Serum from each participant was taken since the date of diagnosis to determine non-enzymatic antioxidants, trace element antioxidants, and peroxidase levels. Each antioxidant level was categorized into quartiles to analyze the correlation with survival time. Both univariate analysis and COX regression model which included nutritional status were used in the analysis.
Results: Thirty patients with mean age of 59.8 (range, 35-82) were enrolled. The majority of patients was male (76%), malnourished (90%), had a history of smoking (80%), and received chemotherapy for treatment of NSCLC (73%). Patients with the highest quartile of zinc had significantly longer survival time than with the lowest quartile (14.7 Vs 5.6 months) in both univariate and multivariate analysis (P = 0.01 and 0.007, respectively); while the significance of manganese was proven in only univariate model. Other antioxidants levels including retinol, α-tocopherol, β-carotene, lycopene, β-cryptoxanthin, selenium, copper, and peroxidase did not demonstrate relationship with survival time.
Conclusion: The low level of some antioxidants, particularly zinc, produced a significantly poor prognosis in advanced-stage non-small cell lung cancer patients.
Citation Format: Kosin Wirasorn, Pranithi Hongprabhas, Veeradej Pisprasert, Kulthida Klarod, Patcharee Boonsiri. Serum antioxidant levels and survival time in advanced non-small cell lung 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 LB-20. doi:10.1158/1538-7445.AM2013-LB-20
Abstract LB-207: Dissecting the functional landscape of triple-negative breast cancer.
Authors: Maxfield Kimberly , Prat Aleix , Corcoran Kathleen , Whitehurst Angelique 
Published: August 2014

Abstract
Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with poor patient prognosis. Patients who respond poorly to the current standard of care cytotoxic chemotherapeutic regimens only have about a 55% five-year survival rate due to the lack of other effective TNBC therapeutics. To uncover new therapeutic entry points for TNBC, we employed a pangenomic loss of function siRNA screening approach. To account for heterogeneity within the patient population, we screened 4 triple negative tumor-derived breast cancer cell lines that represent the spectrum of oncogenic aberrations and molecular subtypes in TNBC. By intersecting the datasets from these 4 cell lines, we revealed core modulators of viability and chemotherapy-induced cellular stress that have not been previously implicated in TNBC biology. For example, our screen uncovered a tractable energy-sensing AMPK family member that supports tumor cell viability in a subset of TNBC tumors. We also discovered tumor cell vulnerabilities unique to the Basal-Like and Claudin-Low TNBC molecular subtypes. In particular, Basal-Like tumor cell division is sensitive to perturbations in specific cytokine signaling. With respect to Claudin-Lows, we found an increased sensitivity to depletion of transcriptional modulators and downstream targets of TGFβ signaling, which suggests that TGFβ signaling may not only be required for a mesenchymal phenotype but also for Claudin-Low tumor cell survival. Our findings suggest that a set of tumor cell vulnerabilities can partition TNBC into functional subgroups and these vulnerabilities could lead to new therapeutics improving overall TNBC patient prognosis.
Citation Format: Kimberly Maxfield, Aleix Prat, Kathleen Corcoran, Angelique Whitehurst. Dissecting the functional landscape of triple-negative breast 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 LB-207. doi:10.1158/1538-7445.AM2013-LB-207
Abstract LB-215: Concomitant targeting of tumor cells and induction of T cell response synergizes to effectively inhibit trastuzumab-resistant breast cancer.
Authors: Wang Qingfei , Li Shau-Hsuan , Wang Hai , Xiao Yi , Sahin Ozgur , Brady Samuel W. , Li Ping , Jaffee Elizabeth M. , Hortobagyi Gabriel N. , Yu Dihua 
Published: August 2014

Abstract
Introduction: Trastuzumab is an iconic example of rationally designed targeted therapy for HER2-positive breast cancers; however, trastuzumab resistance is a imposing clinical challenge that calls for novel approaches to better benefit patients. The purpose of this study was to find alternative combinatorial targeted therapies to overcome trastuzumab resistance.
Methods: We used two distinct PTEN-loss mediated trastuzumab resistant mammary tumor mouse models. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and Akt inhibitor triciribine (TCN) were applied alone or in combination with 7.16.4 antibody, the mouse equivalent of the trastuzumab, for the treatment of tumor-bearing mice. Immunoblotting, immunohistochemistry, in vivo cytotoxicity assay and quantitative real time PCR were employed to dissect the in vivo effects of the treatments and molecular changes.
Results: Concomitant targeting of tumor cells with Akt inhibitor TCN plus trastuzumab, and activation of T cells with anti-CTLA-4 antibody in the tumor microenvironment results in a synergistic inhibitory effect on tumor growth and overcomes trastuzumab resistance in both mammary tumor mouse models. In vivo combinatorial treatment with the 7.16.4 HER2/Neu antibody and TCN effectively inhibited tumor growth in both models via inhibiting PI3K/AKT and MAPK signaling accompanied by increased T cell infiltration in the tumor microenvironment. We demonstrated that both CD8+ and CD4+ T cells were essential to the optimal antitumor effect of the combination treatment in an IFN-γ-dependent manner. Importantly, the antitumor activities of HER2/Neu antibody and TCN combination treatment were further improved when we blocked co-inhibitory receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to enhance the T cell response.
Conclusion: Our data indicate that multi-targeted combinatorial therapies targeting tumor cells and concomitantly enhancing T-cell response in the tumor microenvironment cooperated to exert maximal therapeutic activity. We propose that concomitant targeting tumor cells and tumor microenvironment is a promising clinical strategy for treating trastuzumab-resistant breast cancers and other advanced malignancies.
Citation Format: Qingfei Wang, Shau-Hsuan Li, Hai Wang, Yi Xiao, Ozgur Sahin, Samuel W. Brady, Ping Li, Elizabeth M. Jaffee, Gabriel N. Hortobagyi, Dihua Yu. Concomitant targeting of tumor cells and induction of T cell response synergizes to effectively inhibit trastuzumab-resistant breast 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 LB-215. doi:10.1158/1538-7445.AM2013-LB-215
Abstract LB-223: A specific Isoform of Gli1 binds the promoter region of c-fos in A2780-CP70 human ovarian cancer cells.
Authors: Amable Lauren , Kudo Kenji , Gavin Elaine , Fain Jason , Reed Eddie 
Published: August 2014

Abstract
The transcription factor Activator Protein 1 (AP1), is an important regulator in cisplatin resistance. AP1 is comprised of the two proteins, c-jun and c-fos. The transcription factor Gli1, a member of the hedgehog signaling pathway, is also an important factor in cisplatin resistance and transcriptionally regulated c-jun. The c-jun interface with Gli1 is mediated by a 130 kDa isoform of Gli1. We have investigated whether Gli1 may regulate c-fos by selectively knocking down Gli1 expression using anti-Gli1 shRNA or by treating cells with a Hedgehog pathway inhibitor, cyclopamine.
A2780-CP70 cells were treated with an IC50 dose of anti-Gli1 shRNA and the changes in RNA and protein levels were analyzed over a 72 hour time course. No changes in the expression of c-jun or c-fos RNA transcripts were observed versus control. Western blot analyses showed Gli1 protein expression was reduced at 24 hours and undetectable at 48 and 72 hours. Sonic hedgehog (Shh) protein levels were dramatically reduced by 24 hours, low but measureable at 48 hours, and undetectable at 72 hours. Indian hedgehog (Ihh) expression increased at 24 hours and remained stable for the remainder of the 72 hour time course.
Treatment of A2780-CP70 cells with an IC50 dose of cyclopamine resulted in a different intracellular response than treatment with Gli1 shRNA. Cyclopamine specifically targets the cell membrane receptor Smoothened. Experiments were performed analyzing RNA and protein expression over a 72 hour time period after treatment with cyclopamine. C-jun and c-fos RNA transcript levels were higher than control 6 hours after treatment and remained high for the duration of the 72 hour experiment. Western blot analyses after cyclopamine treatment showed Gli1 protein expression gradually decreasing during the 72 hours, but were never fully depleted. Expression of Shh increased over 72 hours, while Ihh levels remained stable.
The identical Gli-Binding-Site (GBS) in the c-jun promoter was found in the promoter of c-fos. We investigated whether the Gli1 isoform that binds c-jun, also binds c-fos. Simultaneous Western and Southwestern blots show only one of the known Gli1 isoform binds the promoter of c-fos. Further studies with Chromatin Immunoprecipitation (ChIP) assays confirmed the 130 kDa isoform of Gli1 binds the GBS of the c-fos promoter. We conclude that the 130 kDa Gli1 isoform binds both components of AP1, c-jun and c-fos, and modulates the cellular resistance to cisplatin.
Citation Format: Lauren Amable, Kenji Kudo, Elaine Gavin, Jason Fain, Eddie Reed. A specific Isoform of Gli1 binds the promoter region of c-fos in A2780-CP70 human ovarian cancer cells. [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 LB-223. doi:10.1158/1538-7445.AM2013-LB-223
Abstract LB-228: The identification of recurrent non-coding mutations in melanoma.
Authors: Huang Franklin W. , Hodis Eran , Xu Mary Jue , Kryukov Gregory , Chin Lynda , Garraway Levi A. 
Published: August 2014

Abstract
Cancer genome sequencing efforts have identified many recurrent coding mutations in human cancer genes. To date, non-coding “driver” mutations within regulatory regions have rarely been observed. Here we describe the identification of two somatic mutations within the TERT core promoter that were observed in 71% of melanomas. Each mutation generated a de novo consensus ETS binding motif. Reporter assays showed that these mutations could increase transcriptional activity from the TERT promoter. We observed the same mutations in cancer cell lines from diverse tumor types with preliminary evidence of elevated frequency in bladder and hepatocellular cancer cells. Our findings suggest that somatic mutations in non-coding regulatory regions of the genome may represent important events in carcinogenesis.
Citation Format: Franklin W. Huang, Eran Hodis, Mary Jue Xu, Gregory Kryukov, Lynda Chin, Levi A. Garraway. The identification of recurrent non-coding mutations in melanoma. [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 LB-228. doi:10.1158/1538-7445.AM2013-LB-228