bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1414: Treatment outcome under cetuximab-based therapy and individual ADCC capability in head and neck cancer
Authors: Lo Nigro Cristiana , Lattanzio Laura , Vivenza Daniela , Monteverde Martino , Tonissi Federica , Strola Giuliana , Merlano Marco , Milano Gerard 
Published: July 2016

Abstract
Introduction
Cetuximab is a IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR) used for head and neck squamous cell carcinoma (HNSCC) treatment. In addition to EGFR targeting, cetuximab is able to develop an antibody-dependent cell-mediated cytotoxicity (ADCC), triggered by Fc receptors (Fcγ-R) on Natural Killer cells, macrophages and polymorphonucleated leukocytes.
This prospective study examined the possible prognostic value of cetuximab-mediated ADCC response in a cohort of HNSCC patients.
Patients and Methods
There were 63 patients treated with curative intent with chemo-radiotherapy (CT-RT), associated (N = 39) or not (N = 24) with cetuximab. Peripheral blood samples were collected at start of therapy. Intrinsic ADCC was evaluated from ex vivo NK-dependent activity measuring LDH release through the Cytotox 96® non radioactive cytotoxicity assay, previously standardized in our laboratory (Crit Rev Oncol Hematol, 2015). EGFR tumoral expression was analyzed by immunohistochemistry.
Results
Median ADCC response at treatment start for all patients was 56.1% (range 5-99%). Analysing the whole population, patients with ADCC above the median value (high) showed a better OS as compared to patients with ADCC below the median (low), HR = 0.3827 (95% CI, 0.1464 to 1.000), p = 0.05 (Long-rank Mantel-Cox Test). A sub-group analysis confirmed a possible link between high ADCC and a better OS (CT-RT group, p = 0.223 and CT-RT+cetuximab group, p = 0.244).
Importantly, considering CT-RT+cetuximab treatment and EGFR tumoral expression (N = 21), patients with EGFR 3+ status and high ADCC showed an improved OS as compared to patients with ADCC below median value, HR = 0.09031 (95% CI, 0.009983 to 0.8170), p = 0.032 (Long-rank Mantel-Cox Test). Median OS values for patients with high EGFR expression were 34.8 months (range 9.1-53.7) and 13.1 months (range 2.1-39.5) for patients with respectively high ADCC and low ADCC.
Conclusion
ADCC is shown to be a strong driver of cetuximab-based therapy outcome in HNSCC. High tumoral EGFR expression and high ADCC confer a particularly long overall survival. These data suggest an ADCC-based and EGFR expression-based precision therapy under cetuximab in HNSCC and open perspectives for NK boosting.
Citation Format: Cristiana Lo Nigro, Laura Lattanzio, Daniela Vivenza, Martino Monteverde, Federica Tonissi, Giuliana Strola, Marco Merlano, Gerard Milano. Treatment outcome under cetuximab-based therapy and individual ADCC capability in head and neck cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1414.
Abstract 1419: Characterization of the evolution of immune response in lung squamous carcinogenesis
Authors: Mascaux Celine , Angelova Mihaela , Beane Jennifer , Hijazi Kahkeshan , Antoine Geraldine , Willard Gallo Karen , Ninane Vincent , Burny Arsène , Sculier Jean-Paul , Spira Avrum , Galon Jérôme 
Published: July 2016

Abstract
Molecular profiling of from pre-invasive bronchial lesions, and particularly the evolution of immune response, may identify promising new biomarkers for early detection and targets for chemoprevention/treatment of lung cancer.
mRNA expression was analyzed (Agilent microarrays) from fresh frozen human bronchial biopsies (N = 122, 77 patients) at successive morphological stages of lung squamous carcinogenesis. Modules of co-expressed genes were identified among the stage associated genes, selected using a linear mixed-effects model adjusting for smoking status, gender, and history of cancer as fixed effects and patient as a random effect. Cell type specific signatures were applied to the genes co-expressed in these modules in order to identify the immune response signal through the stages of lung carcinogenesis.
Genes expression alterations were grouped into 4 successive molecular steps. Based on their behavior across the 4 steps, 8 modules of genes with different patterns were observed: gene modules primarily up-regulated among the early or late steps, up-regulated in a linearly across the 4 steps, as well as down- then up-regulated (biphasic). Genes signing the presence of activating CD8 and CD4 T cells, as well as some memory B cells were progressively and linearly up-regulated from metaplasia through all stages of carcinogenesis. At the later stages, the transition to high-grade dysplasia, the most significant gene expression changes included immune/inflammatory response genes. At this stage a very strong adaptive immune response is noted involving T cells - mainly Th1 and T regulators - and dendritic cells. In addition, immunosuppressive signals, corresponding to negative co-inhibitory molecules, also significantly appears at the high-grade dysplasia stage.
The adaptive CD4/CD8 related immune response starts from the earlier stages (metaplasia) of lung carcinogenesis. The significant modification of inflammatory/immune response genes in association with high-grade lesions suggests, at this critical stage of carcinogenesis, a major role of the surrounding microenvironment with an adaptive immune response, driven by Th1 and Treg cells, and but also, before tumor invasion across the basal membrane, a tumor versus host immunosuppressive response.
Citation Format: Celine Mascaux, Mihaela Angelova, Jennifer Beane, Kahkeshan Hijazi, Geraldine Antoine, Karen Willard Gallo, Vincent Ninane, Arsène Burny, Jean-Paul Sculier, Avrum Spira, Jérôme Galon. Characterization of the evolution of immune response in lung squamous carcinogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1419.
Abstract 1422: Dietary 2-deoxy-D-glucose (2-DG) reduces TLR-4 induced acute inflammation and prevents chronic inflammation driven carcinogenesis
Authors: Pandey Sanjay , Singh Saurabh , Anang Vandana , Shah Dhananjay K. , Seth Saurabh , Bhatt Anant N. , Manda Kailash , Roy Bal G. , Natarajan K , Dwarakanath Bilikere S. 
Published: July 2016

Abstract
Inflammation is a critical component and contributor of carcinogenesis. Toll like receptors (TLRs) are key regulators of innate immunity and inflammatory signaling. Besides various microbe-associated molecular patterns, TLRs can also bind to endogenously generated damage associated molecular patterns (DAMPS) ligands such as heat shock proteins, surfactant protein A18 and homobility group box-1(HMGB1). While HMGB1, a TLR-4 ligand is over-expressed in several human neoplasms, preclinical studies in mouse tumor models have strengthened the role of TLR-4-HMGB1 axis in promoting carcinogenesis. TLR-4 dependent inflammation and stimulation is accompanied with a switch from respiratory to glycolysis dominated metabolism, which is critical for the differentiation and maturation of myeloid cells thus affecting the outcome of an inflammatory disease. In the present studies we investigated the potential of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) as an energy restriction mimetic agent for countering the acute and chronic inflammation which can be employed as a cancer preventive strategy. Oral administration of 2-DG in drinking water (0.4% w/v) for 7 days reduced the diethyl nitrosamine (DEN) induced acute inflammation reflected by reduced the serum levels of TNF(∼4 fold) and IL-6(∼7 fold). when administered chronically, 2-DG reduced the incidence (∼50%) and the number of papillomas (∼84%) in DMBA-TPA skin carcinogenesis model, which correlated with the reduced levels of TNF. In an acute inflammation model established using LPS (a TLR-4 ligand), we observed that 2-DG reduced the systemic and macrophage specific inflammatory response in LPS injected mice. 2-DG (1mM) significantly reduced the levels of co-stimulatory surface markers (CD80 and CD86) and associated ROS and NOS effecter functions in mouse macrophagic cell line (RAW 264.7). These studies suggest that dietary administration of 2-DG can be used as a strategy for preventing acute inflammation and associated carcinogenesis.
Citation Format: Sanjay Pandey, Saurabh Singh, Vandana Anang, Dhananjay K. Shah, Saurabh Seth, Anant N. Bhatt, Kailash Manda, Bal G. Roy, K Natarajan, Bilikere S. Dwarakanath. Dietary 2-deoxy-D-glucose (2-DG) reduces TLR-4 induced acute inflammation and prevents chronic inflammation driven carcinogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1422.
Abstract 1433: A mobile app for health related quality of life and symptom assessment in patients with primary brain tumors in an outpatient oncology clinic
Authors: Rowe Lindsay , Dong Tuo , Armstrong Terri , Mackey Megan , Gilbert Mark , Krauze Andra , Camphausen Kevin 
Published: July 2016

Abstract
Purpose: Primary brain tumors, and their treatments, can have a significant impact on patient quality of life due to altered mentation, mood changes, memory loss, and neurologic deficits. It has therefore been suggested that patient related outcomes need to be included as endpoints for treatment efficacy. The objective of this project was to develop and evaluate a mobile application (GlioNCI), in reporting health-related quality of life measures and symptom scoring in patients with primary brain tumors treated and followed in an outpatient oncology clinic.
Experimental Procedures and Results: Apple's Xcode Integrated Development Environment (IDE) was used to develop GlioNCI using the Swift programming language. The parameters and scores chosen had previously been validated in primary CNS tumors. Medication and steroid use is captured at each encounter, as are seizure characteristics, frequency and management. Health related quality of life questionnaires included portions of the EORTC QLQ-C30, and EORTC QLQ-BN20, and MD Anderson Symptom Inventory Brain Tumor Module, which have been validated in patients with cancer and primary CNS tumors respectively. Patients’ symptoms and effects on function are collected with the Activities of Daily Living scale, and the Instrumental Activities of Daily Living Scale. Mood and mental state were addressed using the Hospital Anxiety and Depression Scale. Separate questionnaires for different encounters and time points in outpatient treatment were included to assess care provider, as well as patient related measures, allowing for flexibility of the app to the needs of both. A mobile app was developed to collect, and archive in a database, input and feedback from both patients and care providers in oncology clinics.
Conclusion: The creation of a patient centered quality of life and symptom assessment mobile app, following patients with primary brain tumors over their course of treatment and in follow-up is feasible. Pilot testing and patient evaluation of the application in an oncology clinic will be used to validate GlioNCI as a tool in outpatient clinics.
Citation Format: Lindsay Rowe, Tuo Dong, Terri Armstrong, Megan Mackey, Mark Gilbert, Andra Krauze, Kevin Camphausen. A mobile app for health related quality of life and symptom assessment in patients with primary brain tumors in an outpatient oncology clinic. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1433.
Abstract 1438: Preserving genital nerve function in prostate cancer: imaging with a molecular imaging agent
Authors: Le Roux Lucia , Ramos Daniela , Flores Leo , Schellingerhout Dawid 
Published: July 2016

Abstract
Purpose: To establish proof-of-concept for the use of a molecular nerve imaging agent in demonstrating nerve tissue at risk during prostate surgery, and thus preventing iatrogenic sexual dysfunction. Erectile Dysfunction (ED) is a common complication of all forms of prostate cancer treatment, with incidence varying from 13-97% depending on the series quoted. There is broad agreement that treatment related damage to the neurovascular bundles is a root cause of the condition, with strong indications from many studies that preservation of the neurovascular bundles avoids post-treatment ED. The goal of this study is to use a novel neural imaging agent based on the non-toxic Tetanus Toxin C-fragment (TTc) to allow the visualization of the anatomy of the genital nerves, thus facilitating nerve-sparing therapies.
Materials and methods: C57 Black male mice were anaesthetized (1-2% isofluorane/oxygen) and injected with 40 μg/10 μl of fluorescently labeled TTc790 in the tunica albuginea of the left corpus cavernosum. Animals were imaged live over a period of 3 hours post injection with a Xenogen IVIS 200 small animal imager. Animals were then euthanized, and the complete male reproductive system was surgically exposed and imaged ex-vivo with a Zeiss AxioZoom16 dissection microscope. The cavernosal nerves, prostatic tissue with intact nerve plexi were dissected and prepared for cryo-sectioning followed by fluorescent immuno-histology using standard methods.
Results: En bloc excision of the prostate with the penis allowed imaging of the genital nerves using the retrograde transported neural marker, TTc790. We noted fluorescent TTc-related signal uptake along the expected course of the nerve tract ipsilateral to the injection site, and were able to clearly demonstrate the pelvic ganglion within the capsule of the prostate. Immuno-histological assessment with post cryo-sectioning confirmed our surgical microscopy findings, including our demonstration of the pelvic ganglion.
Conclusions: We demonstrate the use of TTc790 as a nerve imaging agent for showing the anatomy of the cavernosal nerves and pelvic ganglion complex by intra-operative fluorescent imaging. This suggests that, with further work, image guidance could be provided to physicians and surgeons to spare these nerves during prostate carcinoma treatments, allowing the preservation of genital nerve function and improving quality of life in prostate cancer survivors.
Citation Format: Lucia Le Roux, Daniela Ramos, Leo Flores, Dawid Schellingerhout. Preserving genital nerve function in prostate cancer: imaging with a molecular imaging agent. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1438.
Abstract 1457: Regulatory T cells and its impact on prostate cancer development and clearance
Authors: Kumar Sanjay , Stokes James , Scissum Gunn Karyn , Singh Udai , Ponnazhagan Selvarangan , Mishra Manoj K. 
Published: July 2016

Abstract
Prostate Cancer (PCa) is the most common non-skin malignancy and the most commonly diagnosed cancer in men in United States. The immunotherapeutic role of immune cells in regulation of PCa have been studied but still the specific roles of regulatory T cells needs further investigation. In this study, the role of immune cells, particularly the role of regulatory T cells, in tumor development and progression was analyzed using TRAMP (transgenic adenocarcinoma of mouse prostate) model system. TRAMP cells (TRAMP C1, C2 and C3) were used to induce tumor in C57/B6 mouse. Interestingly, the TRAMP-C3 is non-tumorigenic whileTRAMP-C1 and TRAMP-C2 are tumorigenic. Briefly, tumor induction studies were performed on different groups of mice. Mice were inoculated with these three cell lines, tumors were analyzed at different time points, and the percentage and absolute number of different immune cells (CD4, CD8, NK, NKT, Macrophages, regulatory T cells, and Dendritic cells) were analyzed. Our data demonstrated that the capacity of TRAMP-C1 and TRAMP-C2 cells to form tumors and the inability of TRAMP-C3 cells to induce tumors is mediated by number of regulatory T cells in the tumor microenvironment. Therefore, the data suggest an understanding of function and effect of regulatory T cells during tumor progression and clearance is needed to successfully develop a targeted therapy to modulate the number of immune cells in the tumor microenvironment.
Citation Format: Sanjay Kumar, James Stokes III, Karyn Scissum Gunn, Udai Singh, Selvarangan Ponnazhagan, Manoj K. Mishra. Regulatory T cells and its impact on prostate cancer development and clearance. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1457.
Abstract 1458: Toll-like receptors 1, 2, 4 and 6 expression levels in diffusely infiltrative astrocytomas
Authors: Moretti Isabele F. , Franco Daiane Gil , Silva Roseli , Galatro Thais F. , Oba-Shinjo Sueli M. , Marie. Suely K.N. 
Published: July 2016

Abstract
Toll-like receptors (TLRs) are the first receptors of the immune system that identify disturbances in homeostasis, capable of recognizing molecules associated to cell and tissue damage. TLRs signaling pathway activates inflammatory transcription factors, mainly Nuclear Factor-kappa B (NF-kB) and Interferon Regulatory Factors (IRF3/7). Due to their importance in inflammatory process, TLRs are research hot targets for therapy in several diseases, including cancer. This study aims to analyze TLRs (1, 2, 4 and 6) expressions in human diffusely infiltrative astrocytomas, WHO grades II to IV of malignancy (AGII-AGIV), and correlate their expressions among them and with the clinical outcome of AGIV (glioblastoma, GBM) patients. TLRs mRNA levels were evaluated by qRT-PCR in 143 astrocytoma samples and 22 non-neoplastic (NN) brain specimens from epilepsy surgery. Upregulated mRNA levels of all studied TLRs were observed in astrocytomas compared to NN cases (p&lt;0.05), except for TLR2 in AGII. TLR1 and TLR2 median expression values increased according to astrocytoma malignancy. TLRs mRNA expressions presented positive correlation with significance (p&lt;0.05) in all grades of astrocytoma, except for TLR2 and TLR4 in AGIII. Strong associations (r&lt;0.7) were detected with TLR1-TLR2 mRNA expressions among AGII, AGIII and AGIV, TLR1-TLR4 in AGIII, and TLR6-TLR1 in AGII. In GBM patients, TLR2 upregulation was associated to better outcome with longer overall survival (p&lt;0.007). The same was verified for concomitant upregulation of TLR1, 2 and 4 (p&lt;0.05). Aiming to analyze the distribution of these receptors in different cells present in the tumor, we performed immunofluorescence staining of GBM cell lines (A172 and U87MG). All TLRs were detected in both cell lines, indicating that their expression were not limited to immune cells. The current literature has described controversial roles for the TLRs in cancer, either activating an anti-inflammatory condition leading to tumor progression or a pro-inflammatory state leading to tumor abrogation. TLRs distribution among different cells in the tumor environment might be relevant for the inflammatory process. Our findings of TLRs on tumor cells may suggest a tendency towards an anti-inflammatory state. The comprehension of TLRs role in each cell type, that compose the tumor, may help to determine the signaling pathways involved in diffusely infiltrative astrocytoma progression, and potential new therapeutic strategies.
Citation Format: Isabele F. Moretti, Daiane Gil Franco, Roseli Silva, Thais F. Galatro, Sueli M. Oba-Shinjo, Suely K.N. Marie. Toll-like receptors 1, 2, 4 and 6 expression levels in diffusely infiltrative astrocytomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1458.
Abstract 151: Modeling the rise of intratumoral heterogeneity in growing, static, and regressing human colorectal polyps
Authors: Sievers Chelsie K. , Zou Luli , Pickhardt Perry J. , Matkowskyj Kristina A. , Albrecht Dawn , Kim David H. , Moawad Fouad J. , Cash Brooks D. , Reichelderfer Mark , Newton Michael A. , Halberg Richard B. 
Published: July 2016

Abstract
Benign adenomatous colon polyps are thought to be transformed into cancers through the stepwise accumulation of mutations. However, not all polyps progress. A significant number remain static in size, regress, or resolve completely. The mechanisms underlying these differential fates are unknown, and currently there are no biological characteristics that can reliably predict which polyps will grow or progress into invasive cancer. To determine the mutational landscape, targeted next generation sequencing was performed on a unique collection of small (6-9mm) colorectal polyps with known growth rates based on interval imaging with CT colonography. To determine spatial location of identified mutations within a polyp, micro-dissection was performed followed by quantitative PCR to validate low frequency mutations. The mutational landscape of small polyps is varied both within and among individual polyps. Polyps carried 0-3 pathogenic mutations with the most frequent being in APC (67%, 32/48), KRAS/NRAS (17%, 8/48), BRAF (17%, 8/48), FBXW7 (10%, 5/48), and TP53 (8%, 4/48). Additionally, 13% (6/48) contained driver mutations at varied mutant allele frequencies, indicating the presence of subclonal populations. In silico modeling of tumor growth was used to determine the likely size at which additional driver mutations arose in order to observe those varied frequencies. This model of colon tumor growth was adapted so that mutations occur with a given probability of 10−5, which may change the fitness positively or negatively, and the lineage from these mutant subpopulations was tracked during tumor growth. In silico polyps were sectioned and mutant allele frequency was recorded and compared to the frequencies observed from the targeted sequencing of human polyps. Contrary to the slow step-wise accumulation of mutations theory, these data indicate small colonic polyps can have multiple pathogenic mutations in crucial driver genes that arise early in a tumor's existence. Understanding the molecular pathway of tumorigenesis and clonal evolution in polyps that are at risk for progressing to invasive cancers will allow us to begin to better predict which polyps may be more likely to progress into adenocarcinomas and which patients are predisposed to developing advanced disease.
Citation Format: Chelsie K. Sievers, Luli Zou, Perry J. Pickhardt, Kristina A. Matkowskyj, Dawn Albrecht, David H. Kim, Fouad J. Moawad, Brooks D. Cash, Mark Reichelderfer, Michael A. Newton, Richard B. Halberg. Modeling the rise of intratumoral heterogeneity in growing, static, and regressing human colorectal polyps. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 151.