tbuckley/cabot-search huggingface dataset:
Abstract 3238: Imbalance of circulating monocyte subsets in patients with squamous cell carcinoma of the head and neck
Authors: Koichi Sakakura, Hideyuki Takahashi, Sei-ichiro Motegi, Kazuaki Chikamatsu
Journal: Cancer Research (2016)

Abstract Introduction: Human circulating monocyte is classified as three populations according to CD14 and CD16 expression: CD14+CD16- classical monocytes, CD14+CD16+ intermediate monocytes and CD14dimCD16+ nonclassical monocytes. Recent studies have unveiled the specific surface molecules and functions of each subset; however their dynamics in patients with cancer still remains unclear. In this study, we evaluated the proportions and the expressions of immunological/angiogenic molecules of the monocyte subsets in peripheral circulation in patients with squamous cell carcinoma of the head and neck (SCCHN). Materials and Methods: Peripheral blood mononuclear cells were isolated from 9 patients with SCCHN and age-matched 4 healthy donors. The 3 monocyte subsets were identified according to CD14/CD16 expressions using multi-color flow cytometry. Mean fluorescence intensities of various HLA molecules and angiogenic markers were analyzed. Results: Percentage of CD14+CD16+ intermediate monocyte among total monocyte tended to decrease in SCCHN patients than that in normal donors (p = 0.079). Higher surface expression of immunosuppressive HLA-G molecule on circulating classical (p = 0.045) and intermediate (p = 0.052) monocyte was observed in patients with SCCHN. An immunosuppressive receptor ILT4 showed tendency to increase on nonclassical monocyte (p = 0.061). Moreover, intracytoplasmic level of milk fat globule-EGF factor 8 (MFG-E8) in association with phagocytosis and angiogenesis tended to increase in intermediate (p = 0.064) and nonclassical (p = 0.052) monocytes of SCCHN patients. Discussion and Conclusion: CD16+ intermediate and nonclassical monocytes have been reported as mature, proinflammatory and angiogenic population in periphery. In the present study, we showed possible alternations of these subsets in patients with SCCHN. Furthermore, increasing surface expressions of immunosuppressive molecules HLA-G and ILT4 on circulating monocytes implied immunological deterioration in cancer patients. However the sample size is still small, our preliminary data strongly suggests proportional and functional changes of peripheral monocyte subsets in SCCHN patients. Further analyses in more patients are currently underway. Citation Format: Koichi Sakakura, Hideyuki Takahashi, Sei-ichiro Motegi, Kazuaki Chikamatsu. Imbalance of circulating monocyte subsets in patients with squamous cell carcinoma of the head and neck. [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 3238.
Abstract 5108: Glucagon like peptide 1 (GLP1) up-regulation in hypoxic and nutrient deprived microenvironment promotes neuroblastoma cell survival
Authors: Umadevi V. Wesley, Nausheen Singh, Robert J. Dempsey
Journal: Cancer Research (2016)

Abstract Introduction: Glucagon-like peptide 1 (GLP1) an incretin has demonstrated to increase insulin secretion in a glucose-dependent manner and is shown to be neuroprotective. GLP1 also promotes angiogenesis. Hypoxia, a common feature in solid tumors including neuroblastoma, promotes tumor progression by upregulation of hypoxia responsive factors. Little is known about alterations of GLP1 expression in neuroblastoma under hypoxic condition. GLP1 is rapidly inactivated by dipeptidyl peptidase IV (DPPIV) mediated enzymatic cleavage. Previously we have shown that DPPIV suppresses neuroblastoma survival and angiogenesis. In this study, we examined whether GLP1, its receptor GLP1R, and DPPIV expressions are altered after exposing neuroblastoma cells to hypoxic conditions of oxygen and nutrient deprivation (OND). We then examined the direct effects of GLP1 on neuroblastoma proliferation and survival, and evaluated if DPPIV modulates GLP1 mediated functions. Methods: We used Neuro-2a, a mouse neuroblastoma cells as a model. In vitro experiments were performed exposing these cells to conditions mimicking tumor areas that display oxygen and nutrient deprivation, followed by re-oxygenation. Immunofluorescence staining was used to analyze the protein expression of GLP1, GLP-1R, and DPPIV. RT-PCR was used to measure mRNA levels. Effects of DPPIV on GLP1 mediated Neuro-2a cell proliferation and survival was evaluated by MTT and live/dead cell assay. Levels of PI3K/AKT were determined by western blot analysis. Results: Neuro-2a cells subjected to OND showed about 2 fold increase in the GLP1 protein and mRNA levels at four hours of re-oxygenation after 4 hours of OND. However, GLP1 protein levels decreased drastically after one day of re-oxygenation, while DPPIV levels were highly upregulated. GLP1R was also downregulated at one day of re-oxygenation. At this time point, cell viability was decreased by 30-40%. Pre-treatment with DPPIV inhibitor rescued the protective effects of GLP1. Furthermore, exogenous GLP1 stimulated cell proliferation and increased Neuro-2a cell viability by 2-3 fold. GLP1dependent action was mediated via increased levels of phosphorylated AKT, a pro-survival signaling molecule. The effects of GLP1 were suppressed in presence of DPPIV. Conclusion: The results indicate an inverse correlation between DPPIV and GLP1 levels in Neuro-2a cells. Together, these studies indicate that GLP1-DPPIV interaction may play an important role in promoting neuroblastoma cell proliferation and survival. Citation Format: Umadevi V. Wesley, Nausheen Singh, Robert J. Dempsey. Glucagon like peptide 1 (GLP1) up-regulation in hypoxic and nutrient deprived microenvironment promotes neuroblastoma cell survival. [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 5108.
Abstract 3423: Overweight and obesity predict better overall survival rates in cancer patients with distant metastases
Authors: Ngan M. Tsang
Journal: Cancer Research (2016)

Abstract Background: Recent studies conducted in patients with chronic diseases have reported an inverse association between body mass index (BMI) and mortality. However, the question as to whether BMI may predict prognosis in patients with metastatic cancer remains open. We therefore designed the current retrospective study to investigate the potential association between BMI and overall survival (OS) in patients with distant metastases (DM) and a favorable performance status. Methods: Between 2000 and 2012, a total of 4,010 cancer patients with DM who required radiotherapy (RT) and had their BMI measured at the initiation of RT were identified. The relation between BMI and OS was examined by univariate and multivariable analysis. Results: The median OS time was 3.23 months (range: 0.1−122.17) for underweight patients, 6.08 months (range: 0.03−149.46) for normal-weight patients, 7.99 months (range: 0.07−158.01) for overweight patients, and 12.49 months (range, 0.2−164.1) for obese patients (log-rank: P &amp;lt; 0.001). Compared with normal-weight patients, both obese (HR = 0.676; 95% P &amp;lt; 0.001) and overweight individuals (HR = 0.84; P &amp;lt; 0.001) had a reduced risk of all-cause mortality in multivariable analysis. Conversely, underweight patients had a significantly higher risk of death from all causes (HR = 1.41; P &amp;lt; 0.001). Conclusions: Overweight and obesity are independent predictors of better OS in metastatic patients with a good performance status. Increased BMI may play a role to identify metastatic patients with superior survival outcome and exhibit a potential to encourage aggressive management in those patients even with metastases. Citation Format: Ngan M. Tsang. Overweight and obesity predict better overall survival rates in cancer patients with distant metastases. [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 3423.
Efficacy and Safety of Pegylated Interferon Alpha-2a in Patients with Essential Thrombocythemia and Polycythemia Vera: Results after a Median 7-Year Follow-up of a Phase 2 Study
Authors: Lucia Masarova, Srdan Verstovsek, Keyur P. Patel, Kate J Newberry, Jorge E. Cortes, Gautam Borthakur, Marina Konopleva, Zeev Estrov, Hagop M. Kantarjian
Journal: Blood (2015)
Abstract 3426: Recurrent breast cancer risk and physical activity
Authors: Teresa A. Lehman, Ramakrishna V. Modali, Luke D. Ratnasinghe
Journal: Cancer Research (2016)

Abstract Introduction: Physical activity reduces the risk of breast cancer. However, the potential role of physical activity in recurrence of breast cancer is not well established. The aim of our study is to examine the association between physical activity and risk of recurrent breast cancer. Methods: Data was obtained from the Global Epidemiological Study (GES). The GES is an IRB approved multinational biorepository and database to assess cancer and other disease risk factors and biomarkers. In-person interviews of all subjects provided demographics, family-history and other disease related information including age, BMI, diet and physical activity. For statistical analyses, t-tests were used for continuous variables and chi-square tests for categorical variables. The association between recurrent breast cancer and physical activity was assessed using logistic regression in univariate and multivariate analyses. Results: From a total of 2435 breast cancer subjects 215 had recurrent breast cancer. The average age of subjects without recurrence was 55.62 years and those with breast cancer recurrence was 58.35 years. In univariate analysis, subjects in the highest tertile of physical activity were 39% less likely to have recurrent breast cancer compared to those who reported no physical activity [Odds Ratio: 0.61, 95% Confidence Interval: 0.40-0.93]. In multivariate analysis, subjects in the highest tertile of physical activity were 45% less likely to have recurrent breast cancer compared to those who reported no physical activity [Odds Ratio: 0.55, 95% Confidence Interval: 0.34-0.89] after adjusting for age, BMI and cancer-stage. A statistically significant dose-response for physical-activity and reduced risk of recurrent breast cancer was observed with a P-value for trend of 0.05. Conclusion: Our study suggests that physical activity reduces the risk of recurrence of breast cancer. Further studies with larger sample size are needed to confirm our findings. Citation Format: Teresa A. Lehman, Ramakrishna V. Modali, Luke D. Ratnasinghe. Recurrent breast cancer risk and physical activity. [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 3426.
Abstract 1041: Glutamine drives glutathione synthesis and contributes to radiation sensitivity of A549 and H460 lung cancer cell lines
Authors: Daniel Sappington, Rosalind Penney, Eric Siegel, Gunnar Boysen
Journal: Cancer Research (2016)

Abstract Increased glutamine uptake is known to drive cancer cell proliferation, making tumor cells glutamine-dependent. Glutamine provides additional carbon and nitrogen sources for cell growth. The first step in glutamine utilization is its conversion to glutamate by glutaminase (GLS). Glutamate is a precursor for glutathione synthesis, and we investigated the hypothesis that glutamine drives glutathione synthesis and thereby contributes to cellular defense systems. The importance of glutamine for glutathione synthesis was studied in H460 and A549 lung cancer cell lines using glutamine-free medium and BPTES a GLS inhibitor. Metabolic activities were determined by targeted mass spectrometry. A significant correlation between glutamine consumption and glutathione excretion was demonstrated in H460 and A549 tumor cells. Culturing in the presence of [13C5]glutamine demonstrated that by 12 hrs &amp;gt;50% of excreted glutathione is derived from glutamine. Culturing in glutamine-free medium or treatment with Bis-2-(5-phenyl-acetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES), a glutaminase (GLS)-specific inhibitor, reduced cell proliferation and viability, and abolished glutathione excretion. Treatment with glutathione-ester prevented BPTES induced cytotoxicity. Inhibition of GLS markedly radiosensitized the lung tumor cell lines, suggesting an important role of glutamine-derived glutathione in determining radiation sensitivity. We demonstrate here for the first time that a significant amount of extracellular glutathione is directly derived from glutamine. This finding adds yet another important function to the already known glutamine dependence of tumor cells and probably tumors as well. Citation Format: Daniel Sappington, Rosalind Penney, Eric Siegel, Gunnar Boysen. Glutamine drives glutathione synthesis and contributes to radiation sensitivity of A549 and H460 lung cancer cell lines. [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 1041.
A Possible Association between the Presence of Interleukin-4-Secreting Cells and a Reduction in the Risk of Acute Graft-Versus-Host Disease.
Authors: Maki Takabayashi, Heiwa Kanamori, Hirotaka Takasaki, Satoshi Yamaji, Hideyuki Koharazawa, Jun Taguchi, Naoto Tomita, Katsumichi Fujimaki, Hiroyuki Fujita, Shin Fujisawa, Atsuo Maruta, Yoshiaki Ishigatsubo
Journal: Blood (2004)
Immunogenomics-based development of personalized immunotherapy for lung cancers.
Authors: Yataro Daigo, Atsushi Takano, Koji Teramoto, Yusuke Nakamura
Journal: Journal of Clinical Oncology (2015)

3019 Background: Oncoantigens are oncogenic and high immunogenicity proteins specifically expressed in cancers, and are promising targets for personalized immunotherapy. Methods: We have established a strategy to identify new oncoantigens; i) screening of genes expressed in the majority of 120 lung cancers with cDNA microarray covering 27,648 genes, ii) verification of no expression of these genes in normal tissues, iii) validation of the clinicopathological significance of their expression with tissue microarray covering 400 lung cancers, iv) characterization of their role in the growth or invasiveness of cancer cells by RNAi and cell growth/invasion assays, v) screening of the epitope peptides recognized by HLA-A*0201- or A*2402-restricted cytotoxic T lymphocyte (CTL) for clinical trials. Results: We identified dozens of 10-amino-acid peptides from 45 oncoantigens, each of which was a candidate to be presented on the surface of HLA-A*0201 or HLA-A*2402 that induced CTL response. We conducted a phase I study for HLA-A*2402-positive, advanced non-small cell lung cancer patients who failed to standard therapy, using the combination of three peptides from LY6K, CDCA1, and KIF20A mixed with adjuvant once a week. 20 evaluable patients have been enrolled, and this cancer vaccine therapy demonstrated tolerability and had very high immunogenicity to induce antigen-specific CTLs in cancer patients. Disease control rate including one complete response was 50%. The patients showing LY6K-specific CTL responses demonstrated a longer overall survival than those without CTL induction. The patients with CTL induction for multiple peptides were likely to show better clinical outcomes. We are also screening predictive and monitoring biomarkers for peptide vaccine therapy through immunogenomics approach by analyzing pattern of CTL response, genomic/proteomic profiles of CTLs, cancer tissues and serum, as well as genetic variation of patients and identified various candidate biomarkers detectable in cancer tissues and/or serum. Conclusions: Current data of the cancer vaccine therapy coupled with screening of companion diagnostics warrants further clinical studies to develop more personalized and effective immunotherapy. Clinical trial information: NCT01069575.
Abstract 2122: Downregulation of RGS10 induces PI3K/mTOR inhibitor resistance by Ras activation in glioblastoma
Authors: Xiaolong Li, Shaofang Wu, Dimpy Koul, W.K. Alfred Yung.
Journal: Cancer Research (2016)

Abstract Glioblastoma multiforme (GBM) is the most common form of malignant brain cancer in adults. The prognosis of affected patients is poor and median survival is only one year. The essential role of PI3K signaling in GBM proliferation, metabolism and differentiation has been highlighted. The major mechanism for the oncogenic activity of PI3K is by preventing apoptosis through the downstream activation of Akt and mTOR. The importance of mTOR in the regulation of cell survival downstream of PI3K signaling provides a strong rationale for the use of dual PI3K/mTOR inhibitor. However, the limited effect of dual PI3K/mTOR inhibitor used as single agent is most likely due to activation of collateral pathways, suggesting that additional refinement of this overall approach is necessary. We investigated potential bypass mechanisms to PI3K/mTOR inhibition as a single agent and generated three resistant cell lines to PI3K/mTOR inhibitor with 3 to 5-fold increase in IC50 value and with an aim to identify the potential bypass of survival to PI3K/mTOR inhibitor. We show that the IC50 of the resistant cell lines and parental lines is correlated with s6 phosphorylation and the three resistant cell lines express increased level of phosphorylated ERK1/2, p70S6K and p90RSK protein levels. Further investigation show that RGS10, a regulator of G protein signaling, is down regulated in the resistant cell lines. Down regulation of RGS10 increases the GTP-bound Ras, implying that Ras activation defines the acquired resistance by activating the ERK/p90RSK pathway. Knockdown RGS10 in the parental cells induces ERK1/2, p70S6K and p90RSK phosphorylation and the resistance to PI3K/mTOR inhibitor. Raf1 or p90RSK knockdown can re-sensitize resistant cell lines to PI3K/mTOR inhibition. Combination of PI3K/mTOR inhibitor with Raf inhibitor Sorafinib efficiently inhibited the growth of the resistant cell lines showing Ras/Raf activation serves as an escape mechanism to PI3K/mTOR inhibition. These observations suggest that Ras/Raf signaling serves as an survival signal upon PI3K/mTOR inhibition and provides a strong rationale for the combined use of PI3K/mTOR and Raf1 inhibition to induce lethal growth inhibition in human GBM. Citation Format: Xiaolong Li, Shaofang Wu, Dimpy Koul, W.K. Alfred Yung. Downregulation of RGS10 induces PI3K/mTOR inhibitor resistance by Ras activation in glioblastoma. [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 2122.
Abstract 2814: Comparative DNA damage and transcriptomic effects of engineered nanoparticles in human lung cells in vitro
Authors: Garret B. Nelson, Sheau-Fung Y. Thai, Carlton P. Jones, Audrey Barbee, Micaela Killius, Jeffrey A. Ross
Journal: Cancer Research (2016)

Abstract A series of six titanium dioxide and two cerium oxide engineered nanomaterials were assessed for their ability to induce cytotoxicity, reactive oxygen species (ROS), various types of DNA damage, and transcriptional changes in human respiratory BEAS-2B cells exposed in vitro at several concentrations for 72 hours. Only limited cytotoxicity was observed at concentrations up to 300 μg/ml for all of the nanomaterials. Small increases in 8-oxo-deoxyguanosine were induced by some of the nanomaterials, but did not achieve statistical significance. No increases in ethenoadenosine or ethenocytidine were detected by ELISA assays for any of the tested nanomaterials. Several of the nanomaterials exhibited concentration related increases in levels of apurinic/apyrimidinic sites, endogenous DNA adducts measured by 32P-postlabeling, lipid peroxidation, and ROS. Consistent with these findings, several of the nanomaterials also affected expression of genes involved in p53, ATM, and mismatch repair pathways. Integrin signaling pathways were also altered by a majority of the nanomaterials tested. There was general agreement between activity in DNA damage assays and extent of pathway transcriptional alteration. One out of the cerium oxide nanomaterials tested did not induce a high enough incidence of differentially expressed genes relative to controls to allow analysis at the pathway level, and also elicited the lowest response in multiple DNA damage assays. Taken together, these data are consistent with the contribution of DNA damage induced by reactive oxygen species as mediators of potentially adverse biological effects following exposure to engineered titanium and cerium oxide nanomaterials, and suggests the utility of short term in vitro tests to predict relative potencies of these particles. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy. Citation Format: Garret B. Nelson, Sheau-Fung Y. Thai, Carlton P. Jones, Audrey Barbee, Micaela Killius, Jeffrey A. Ross. Comparative DNA damage and transcriptomic effects of engineered nanoparticles in human lung cells in vitro. [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 2814.
Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia with Normal Karyotype: A Risk Factor Analysis in 247 Patients, Based On Molecular Markers and Stage at Transplantation.
Authors: Tim Pfeiffer, Michael Schleuning, Matthias Eder, Johanna Tischer, Jan Braess, Donald W. Bunjes, Hildegard Greinix, Gesine Bug, Ernst Holler, Daniel V Oruzio, Marta Krejci, Christof Scheid, Armin Gerbitz, Karin Kolbe, Ralf G Meyer, Renate Arnold, Maximilian Christopeit, Herrad Baurmann, Stephanie v. Harsdorf, Wolfgang Andreas Bethge, Elke Dammann, Margarete Rothmayer, Anne Franke, Susanne Schnittger, Jiri Mayer, Günther Schlimok, Rainer Schwerdtfeger, Arnold Ganser, Hans Jochem Kolb, Christoph Schmid
Journal: Blood (2009)
Case 24-1975
Authors: George L. Nardi, Austin L. Vickery
Journal: New England Journal of Medicine (1975)

Presentation of CaseA 53-year-old man was admitted to the hospital because of chest pain.He was well until four weeks earlier, when he began to experience bouts of substernal pressure that usually followed exertion and subsided in two or three minutes. On the morning of admission severe chest pain developed, accompanied by dyspnea, sweating and abdominal "tightness."An appendectomy had been performed at the age of 15 years, and at 22 years he was operated on for intussusception. Postoperative phlebitis in the left leg was complicated by chronic ulceration. There was no history of hypertension or heart disease. The . . .